PMID- 9633405
TI  - Hungry for peace.

PMID- 9633406
TI  - Nurses who blow he whistle need more support.

PMID- 9633407
TI  - Vile bodies.

PMID- 9633408
TI  - Priceless.

PMID- 9633409
TI  - Taking effect.

PMID- 9633410
TI  - Taking the lead.

PMID- 9633412
TI  - The great escape.

PMID- 9633411
TI  - Florence revisited.

PMID- 9633413
TI  - Men: the hidden crisis.

PMID- 9633414
TI  - Will two become one?

PMID- 9633415
TI  - Hearing aid.

PMID- 9633416
TI  - To err is human to forgive is divine, as one nurse found out.

PMID- 9633417
TI  - Clinical supervision: what's going on? Results of a questionnaire.
AB  - This paper presents data obtained from a questionnaire sent to trust nurse
      executives in England and Scotland. While the data indicates a great deal of
      enthusiasm for clinical supervision, some concern must be shown for the lack of
      preparation and support for those involved in its implementation, a fact that
      will undoubtedly reflect badly in any evaluation exercise.

PMID- 9633418
TI  - Major incidents at large sporting venues.

PMID- 9633419
TI  - A behavioural approach to obsessive compulsive disorder.

PMID- 9633421
TI  - Reducing risks in lifting and handling.

PMID- 9633420
TI  - Managing systemic lupus erythematosus.

PMID- 9633422
TI  - Thoroughly modern leaders.

PMID- 9633423
TI  - It's tough at the top.

PMID- 9633424
TI  - Climbing frame.

PMID- 9633425
TI  - [The concept of paradigm in nursing science].
AB  - This paper critically analyses the use of the term paradigm in nursing science.
      The essay consists of two main sections. The "prekuhnian" meaning of the paradigm
      term is described in the first section. The developments in the philosophy of
      science are presented in conjunction with the rise of the "antipositivist turning
      point" and Kuhn's historical approach with its central terms (paradigm,
      revolution, normal science). Some central points of criticism regarding Kuhn's
      approach close the first section. The second section gives attention to the
      application of the term paradigm in nursing science, at first describing the
      situation in the USA and subsequently referring to Germany. The insufficient
      extent of discussions on questions and problems regarding the philosophy of
      science is elucidated in the following criticism. The examination comes to the
      conclusion that the application of the paradigm term to nursing science is
      neither possible nor is it sensible. A brief review of the prospects for nursing
      science concludes the essay.

PMID- 9633426
TI  - [Reading: a source of information. Study of motivational factors, influencing the
      reading of professional literature in nursing].
AB  - A qualitative research among 13 Dutch nurses working in different areas of
      nursing investigated which factors might influence nurses' motivation (not) to
      read specialist literature. Two central subjects were identified: nurses'
      personal interests and the influence of the environment at work. Analysis of the
      data shows a great influence of the work environment on the individual nurse's
      choice to read specialist literature: the more stimulating the environment is
      towards developing and discussing knowledge, the more nurses make use of
      specialist literature. An individual reason to consult such literature is formed
      by the presence of "search questions", based on incidents in a person's actual
      work situation. Informants report little or no interest in research or studies:
      they only incidentally read abstracts of research findings, and only concerning
      subjects directly linked with their own practice situation. Influence of the work
      environment seems to play an important role on the choice made.

PMID- 9633427
TI  - [Disruptive behavior of elderly residents and the use of nursing methods].
AB  - This study is the first part of a larger research project concerned with
      disruptive behaviour and the use of physical restraints on elderly nursing home
      residents. This paper is focused on the types and prevalence of disruptive
      behaviour among elderly residents, nurses' experiences and the types of nursing
      interventions employed. Data was collected from nurses of varying qualifications
      (n = 173) in seven Swiss nursing homes by using a questionnaire. The most
      frequent behavioural problems reported by nurses were mobility, incontinence,
      getting dressed, verbal communication, passivity, withdrawal and continual
      requests. Nurses found physical aggression, continual shouting and verbal abuse
      the most difficult to manage with. The results also indicated that experiences
      varied between nurses. In particular, nursing staff always considered disruptive
      behaviour more disruptive against other residents rather then against themselves.
      The most frequently used interventions against disruptive behaviour were
      considering residents' wants and needs, getting close, adjustment to residents'
      background and organisation of activities. Physical and chemical restraints were
      also used.

PMID- 9633428
TI  - [Eating and drinking in patients with Alzheimer dementia. A study of
      interactions].
AB  - Eating and drinking become difficult for people afflicted with dementia. We have
      therefore analysed the mealtime constellation in five cases of institutionalised
      people suffering from Alzheimer using video in an open technique. The process of
      eating and drinking entailed intensive interaction between patients and their
      nurses. The demented were apparently in possession of extensive nonverbal
      communicative ability to both transmit and receive signals. It proved possible to
      identify behavioral factors that hinder or benefit the mealtime procedure of the
      analysed cases.

PMID- 9633429
TI  - [Decisions and attitudes of nurses in the care of chronically ill elderly
      patients].
AB  - Data of 182 nurses from two teaching hospitals regarding their attitudes to
      determinants of the decision-making process in elderly patients in general and
      decisions in the treatment of an moderately demented, incompetent elderly man
      with a potentially reversible life-threatening illness using a scenario were
      analyzed. 68.1 percent complied to the patient's will when an advance directive
      existed. One fifth reported that the patient's directive was supportive for the
      decision. The more important the wishes of the patients were evaluated, the more
      frequent a less aggressive treatment choice was preferred and the less frequent
      the decision was for resuscitation in the case of a cardiac arrest. The increased
      use of advance directives is desirable to reduce the number of conflicts in
      decision-making for healthcare professionals and to reduce the patients' fears of
      over- or undertreatment and for increasing their possibilities of self
      determination. A more intensive integration of topics such as death and dying,
      treatment of the chronically ill elderly as well as possibilities and limitations
      of patient directives and their use in the education of nurses is required.

PMID- 9633430
TI  - [Expectations of the nursing profession at the beginning of nursing education and
      their realization at the end of the 2 year (longitudinal study)].
AB  - When young people start a career in nursing, they have certain expectations about
      the profession. The intrinsic motivation of wanting to help plays the most
      important role. Does the nursing profession actually fulfill these expectations
      or will the everyday-routine of the profession soon disappoint the students? In
      the study presented, 166 nursing students were tested twice, once at the
      beginning of their education (Veit, 1996) and after having completed their second
      year of training. The comparison of the results of both surveys enables us to
      determine to which extent the expectations connected with the choice of a career
      were actually fulfilled. On the whole, the students participating in the survey
      were satisfied with their career choice. The degree to which their expectations
      were fulfilled, however, vary according to the different groups of students.

PMID- 9633431
TI  - [When antiquated methods change].

PMID- 9633432
TI  - [50 years of Pflegezeitschrift. "Contemplations on the restlessness of everyday
      life"].

PMID- 9633433
TI  - [The owner of an old-age home defends himself against the dictates of the nursing
      insurances: the new culture of assistance before the Kadi].

PMID- 9633434
TI  - [Introducing juridic opinion for the nursing profession: the opinion is marking
      the entrance into the labyrinth of the juridic system].

PMID- 9633436
TI  - [Conference "Hommage to Sister Liliane Juchli in Kassel/Baunatal: "Harness your
      chariot to the stars"] [In Process Citation]

PMID- 9633435
TI  - [The neonatologic intensive care unit at the Stuttgart Olga Hospital. A cheerful,
      childlike outfit next to extensive high-tech equipment].

PMID- 9633437
TI  - [Microbial infections from the water bottle: still waters can give you a
      bellyache].

PMID- 9633438
TI  - [Local anesthetics and their use: special anesthetic measures are available for
      the extremities].

PMID- 9633439
TI  - [Sexuality and disease: sometimes taboos are broken].

PMID- 9633440
TI  - [Surgical interventions in the aged. 1. Old age is no contraindication].

PMID- 9633441
TI  - [The unit work place, supported by electronic data processing: which requirements
      do hardware and software have to meet?].

PMID- 9633442
TI  - [Evaluation of co-workers. 2. Sources of error must be recognized and avoided].

PMID- 9633443
TI  - [Quality features and standards for personnel developing measures:
      interprofessional discipline and professionality are the focus].

PMID- 9633444
TI  - [Professional fatigue: a review of literature and implications for nurses].
AB  - The objective of this paper is to present literature revision of the factors
      which contribute to the professional hospital nurse fatigue. Burnout Syndrome,
      which is specific of the professionals who work directly with clients, like the
      hospital nurses, was chosen as a focus of study. The Burnout Syndrome is
      characterized by three fundamental symptoms: the sentiment of emotional fatigue,
      personal withdrawal and the reduction of professional achievement. In addition,
      the main associate variables were studied, and grouped in three categories:
      personal, organization and the work structure variables.

PMID- 9633445
TI  - [Notes about the historical evolution of health policies in Brazil].
AB  - This paper is an historical review of the health policy in Brazil. Ranged since
      the arrival of the real portuguese family to Brazil until nowadays. The review
      intent to contextualize present facts based on historical, social and political
      facts for the needed foundation to give best comprehension of the ways in which
      is organizing the health policy in Brazil.

PMID- 9633446
TI  - [Relationship between gender and holistic representations of health and illness].
AB  - The article examines the relations that may exist between gender and holistic
      representations of health and illness having medicine flower as approach's
      parameter. It presents a short traditional medicine history and the appearance of
      alternative therapeutic practice. By understanding gender like a process of
      social construction it suggests a theoretical account proposition that explains
      the majority presence of women between users and flower therapists.

PMID- 9633447
TI  - [Paternity in the perspective of a group of fathers].
AB  - Looking upon occidental silence which involves the paternity, we performed this
      research with the intention to conceive some associated aspects: the family role,
      birth of son expectation and father social role. For that, 7 fathers have been
      interviewed with ages between 21 and 45 years. This study allowed us observed
      that the paternity of the interviewed fathers is experienced by the father-son
      relationship preoccupation, kids education and the constant search of ways to
      experience the paternity as a form to be near of the kids and the wife.

PMID- 9633448
TI  - [How nurses evaluate home nursing and family caregivers].
AB  - The aim of this study was to assess the way used by nurses for evaluate the
      family care and the caregiver. The method used was a quali-quantitative one. A
      semi-structure interview was the instrument chosen to collect data. It was
      applied to 20 (twenty) nurses from a University Hospital within the months of
      April and May, 1996. Data analysis was based on the Bardin's Content Analysis
      Technique (1994). The results demonstrated that nurses are not systematic in
      evaluating family care and the caregiver, but they use their intuition, based on
      momentaneous decisions. This reveal a difficulty of integration between the
      formal and the informal care caused by lack of interaction or effective
      valorization of the family care process.

PMID- 9633449
TI  - [Professional fatigue: empirical study with hospital nurses].
AB  - This is a empirical approach about professional fatigue of the hospital nurse.
      The fatigue concept was based on the Burnout Syndrome and some hospital variables
      associated. The sample consisted of 341 nurses of whom demographic data is
      available. Results of the application of the psychometric analysis of Burnout
      Inventory, as well as statistic correlation between the three scales and
      demographic data are presented. Considerable presence of emotional exhaustion and
      cognitive weariness as a consequence of the working atmosphere in the hospital
      critical sectors and the nursing chief responsibility were found.

PMID- 9633450
TI  - [Students opinion about the administration of adult assistance].
AB  - This article describes the student's opinion about the discipline Administration
      of Adult Nursing Assistance, developed in the 7th term of nursing graduation
      course in UFRGS Nursing School. The aspects evaluated were: organization,
      objectives, theoretical framework, subjects relevance, teaching strategies, field
      of practice learning and supervision. It's a qualitative study, the instrument
      used is a questionary with open questions, which allows the students write their
      points of view about the discipline. The population selected was all students of
      7th term of course in 1996/1 and 1996/2 (77 students), but only 34 students
      answered the instrument. The data were analyzed by Bardin (1977) conteud analysis
      approach.

PMID- 9633451
TI  - [Violence: a social ill or the coded expression of an expectation].

PMID- 9633452
TI  - [Aggression, violence, how to deal with them].

PMID- 9633453
TI  - [The violent interlocutor and the professional].

PMID- 9633454
TI  - [Institutional policies on violence].

PMID- 9633455
TI  - [The Public Assistance--Hospitals of Paris: an institution fighting violence.
      Interview by Isabelle Levy].

PMID- 9633456
TI  - [Violence in psychiatric emergencies. Improving and making the best of the care
      of a violent patient].

PMID- 9633457
TI  - [Violence as a counter attitude].

PMID- 9633458
TI  - [Establishment of accreditation. The patient's expectations].

PMID- 9633459
TI  - [A booklet on patient admission in ophthalmology].

PMID- 9633460
TI  - [In order to be happy, let us relax].

PMID- 9633461
TI  - [Esthetic care in a Center for the Fight Against Cancer].

PMID- 9633462
TI  - [The responsibility of nursing students within the facilities who accept them
      during their training].

PMID- 9633463
TI  - [Effects of drug distribution, entero-hepatic cycle, bioavailability].

PMID- 9633464
TI  - [Critical ischemia of the legs and vascular rehabilitation. Holistic care].

PMID- 9633465
TI  - [Nursing spring. Seasonal temperatures lower than normal].

PMID- 9633466
TI  - [Parkinson's disease].

PMID- 9633467
TI  - [Falls in the elderly].

PMID- 9633468
TI  - [Psychogeriatric emergencies in the general hospital].

PMID- 9633469
TI  - [Glaucoma in the elderly].

PMID- 9633470
TI  - [Treatment of malnutrition].

PMID- 9633471
TI  - [The Program for Medical Information Systems. After care or rehabilitation.
      Example of organization in a geriatric services].

PMID- 9633472
TI  - [Familiarity in addressing institutionalized patients].

PMID- 9633473
TI  - [Dementia, memory and identity].

PMID- 9633474
TI  - [The team is like a living being].

PMID- 9633475
TI  - [Preparing a meal. Improving the utensils].

PMID- 9633476
TI  - [Psychomotor practice in geriatric psychiatry].

PMID- 9633477
TI  - [Living places. Admission of the elderly into families].

PMID- 9633478
TI  - [Malaise in newborns].

PMID- 9633479
TI  - [Gastroesophageal reflux. Nursing surveillance].

PMID- 9633480
TI  - [Gastroesophageal reflux. pH measurement].

PMID- 9633481
TI  - [Gastroesophageal reflux. Surgical treatment using laparoscopy. Indications and
      principles].

PMID- 9633482
TI  - [Gastroesophageal reflux. Pre- and postoperative care].

PMID- 9633483
TI  - [Psychological stress of professionals].

PMID- 9633484
TI  - [The temptation of a sacrificial position].

PMID- 9633485
TI  - [Tracheotomy and nursing care in children].

PMID- 9633487
TI  - [Rowing against stress].

PMID- 9633489
TI  - Technological infusion! Medical diffusion. Personal confusion?

PMID- 9633488
TI  - [Secure plan in maternity hospitals].

PMID- 9633490
TI  - The role of video-assisted vascular surgery.

PMID- 9633491
TI  - A scoring system to predict the outcome of long femorodistal arterial bypass
      grafts to single calf or pedal vessels.
AB  - OBJECTIVES: The aim of this study was to develop a scoring system to predict the
      outcome of long femorocrural and femoropedal bypass grafts performed for critical
      limb ischaemia. SETTING: Teaching hospital. METHODS: An analysis of 109
      consecutive femorodistal bypass grafts performed for critical lower limb
      ischaemia between June 1991 to December 1994. Factors shown to affect the outcome
      were: inflow, number of patent calf vessels, graft material, straight flow to the
      foot and patent pedal vessels. These variables were weighted according to their
      relative significance (multivariate Cox regression) and a scoring system (ranging
      from 0 to 10) was developed. RESULTS: Patients with a preoperative score of 0-4
      (n = 35) showed a secondary patency of 36% at 1 month, 12% at 3 months and 0% at
      10 months (Cum SE = 6.90/0.0). Secondary patency rates for the 46 patients with
      score 5-7 were 88.7% at 3 months, 56.3% at 12, and 45.1% at 2 and 3 years (Cum SE
      = 9.82), while the respective values for the 28 patients with score 8-10 were
      92.7%, 88.5% and 81.7% (Cum SE = 8.08). The difference was highly significant (p
      = 0.000) in all tests of equality. In addition, the median total hospital cost
      was 12,600 Pounds for the group 0-4 compared with 8100 Pounds (group 5-7) and
      4400 Pounds (group 8-10) (p = 0.0085). CONCLUSIONS: This preoperative scoring
      system appears to correlate well with the outcome of distal revascularisation to
      single calf or pedal vessels. If applied to patient selection, it could
      significantly reduce the total hospital cost per leg saved. A prospective testing
      of its predictive ability is needed and is in progress.

PMID- 9633492
TI  - Intraoperative high resolution duplex imaging during carotid endarterectomy:
      which abnormalities require surgical correction?
AB  - OBJECTIVES: This study evaluates high resolution, duplex ultrasound imaging for
      quality control of carotid endarterectomy in order to determine which technical
      factors were linked to residual stenosis and to define duplex criteria for re
      exploration. DESIGN, MATERIAL AND METHODS: A consecutive series of 100 patients
      undergoing carotid endarterectomy were evaluated. Duplex imaging was performed
      prior to wound closure and repeated at 6-8 weeks postoperatively. Stenoses were
      classified as non-significant, moderate or severe based on duplex criteria.
      Intimal flaps, shelves, kinks, clamp damage and fronds were identified by
      ultrasound imaging. RESULTS: Five moderate stenoses were noted in the proximal
      endarterectomy site (PES), and at follow-up three had resolved. Adherent fronds
      were detected in 83% of vessels and resolved in all but three cases. At the
      distal endarterectomy site there were 10 severe and 12 moderate stenoses. Intimal
      flaps were associated with an increased incidence of residual stenosis (p =
      0.010). CONCLUSIONS: We conclude that severe stenoses with an intimal flap should
      be corrected immediately. Further data is required to establish the significance
      of kinks. Residual intimal flaps in the PES appear to remodel. The role of
      completion duplex may lie in the modification of surgical technique to eradicate
      anatomical and haemodynamic imperfections.

PMID- 9633493
TI  - The progression and correction of duplex detected velocity shifts in
      angiographically normal vein grafts.
AB  - OBJECTIVES: To review the sensitivity of duplex scanning and angiography at
      detecting vein graft stenoses in patients on a graft surveillance programme.
      DESIGN: Prospective, open, non-randomised study. PATIENTS AND METHODS: Since
      February 1993, 143 patients with 148 grafts (70% in situ, 30% reversed) have
      attended postoperative infrainguinal vein graft surveillance for a minimum of 6
      weeks. Fifty-seven graft stenoses in 57 grafts were identified by duplex scanning
      as a localised high velocity jet. Angiography was performed in all except 12
      patients. RESULTS: Angiography confirmed a duplex abnormality in all but 10
      patients. Of these, five patients remain stable and asymptomatic with a
      persisting duplex abnormality. The remaining five patients, although
      asymptomatic, exhibited disease progression on duplex and surgical intervention
      confirmed significant stenoses, which were successfully treated. CONCLUSION: The
      results suggest that duplex scanning is a reliable imaging modality for detecting
      vein graft stenoses. Selection for surgical correction can be made, in some
      circumstances on the basis of clinical and ultrasound criteria alone.

PMID- 9633494
TI  - Postoperative fever, bowel ischaemia and cytokine response to abdominal aortic
      aneurysm repair--a comparison between endovascular and open surgery.
AB  - OBJECTIVES: To study bowel ischaemia in transfemorally placed endoluminal
      grafting (TPEG) for abdominal aortic aneurysms, and any relation to cytokine
      response or postoperative fever. DESIGN: Prospective not randomised. University
      hospital setting. MATERIAL: Fourteen cases of conventional surgery and 23 cases
      of endovascular technique for infrarenal abdominal aortic aneurysm repair.
      METHODS: Tonometry was used for sigmoid colon pH, and ELISAs for serum IL-6.
      RESULTS: Mucosal pH in the sigmoid colon fell significantly during clamping and
      reperfusion in both groups. Lowest measured sigmoid colon pH was 7.10 in the open
      group, compared to 7.22 in the TPEG group (p < 0.05). The IL-6 levels in serum
      peaked after 4 h of reperfusion; 249 pg/ml in the open group, compared to 89
      pg/ml in the TPEG group (p < 0.05). High levels of IL-6 in the postoperative
      period and persisting low sigmoidal pH were associated with serious
      complications. Postoperative temperature did not differ significantly between the
      groups, and no significant correlation could be found with sigmoid colon pH or IL
      6 levels. CONCLUSIONS: The less pronounced perioperative bowel ischaemia in TPEG
      patients indicates an advantage of the TPEG technique. Splanchnic ischaemia was
      not related to postoperative fever, nor the IL-6 or TNF response.

PMID- 9633495
TI  - Importance of graft configuration in outcome of endoluminal aortic aneurysm
      repair: a 5-year analysis by the life table method.
AB  - AIM: The aim of this study was to determine the influence of graft configuration
      on the outcome of endoluminal repair of abdominal aortic aneurysm (AAA). METHODS:
      The 5-year study period extended from May 1992 to May 1997 and included analysis
      of patients undergoing endoluminal AAA repair in the first 4.5-year period with a
      minimum follow-up period of 6 months. Between May 1992 and November 1996 136
      patients underwent endoluminal AAA repair. Two patients who had endoluminal
      repair of anastomotic AAA and six patients who had secondary endoluminal repair
      of AAA were excluded, leaving 128 patients in the study group. There were 117
      males and 11 females with a mean age for the group of 71 years. The configuration
      of the grafts was tubular aortic (T) (n = 50), tapered aortoiliac/femoral (AI) (n
      = 24) and bifurcated (B) (n = 54). Patient characteristics and co-morbidities
      were similar in the three groups. The procedures were performed in the operating
      room under radiographic control. Follow-up was complete and consisted of regular
      physical examination and contrast enhanced computed tomography. Outcome measures
      were perioperative mortality rate, need for conversion to open repair, presence
      of early and late endoleaks, successful exclusion of AAA from the circulation,
      and survival. Data were analysed by the life table method. RESULTS: There was no
      significant difference in perioperative mortality for T (4%), AI (4%) and B
      (5.5%) configuration of endograft. Outcome for T, AI, and B configurations was
      respectively: primary conversion (%) 8, 12, 13; early endoleaks (n =) 5, 0, 1;
      late endoleaks (n =) 7, 0, 1. The overall incidence of failed procedures
      throughout the study period was higher in tube grafts compared with non-tube
      (aortoiliac and bifurcated) grafts (p < 0.05). Kaplan-Meier curves demonstrated a
      success probability at 40 months of 50% for tube grafts and 80% for non-tube
      grafts. However, a comparison of the time to procedure failure between tube
      versus non-tube after adjusting for competing risks (death without prior graft
      failure) was non-significant (p = 0.14). CONCLUSIONS: The poor mid-term outcome
      for tube prostheses requires a reassessment of the criteria for selecting this
      configuration. It would be unwise to abandon the use of tube prostheses entirely
      in endoluminal repair. With increasing information on mid and long-term outcome
      of endoluminal AAA repair it is likely that there will be an increasing
      acceptance of treating smaller AAA while they are still suitable for treatment by
      the endoluminal method and most likely with tube grafts. A tightening of the
      criteria for using tube prostheses would seem sensible. In particular, the
      minimum length of distal neck required for endoluminal tube graft repair should
      be increased to the 2-2.5 cm range.

PMID- 9633496
TI  - Clinicopathological evidence that neovascularisation is a cause of recurrent
      varicose veins.
AB  - OBJECTIVES: Recurrent varicose veins may result from poor initial surgical
      technique or progression of varicosities in collateral veins. In some cases new
      veins may develop at the saphenofemoral junction (neovascularisation) and cause
      recurrent saphenofemoral incompetence. This was a histological study of recurrent
      varicose veins. DESIGN: This clinicopathological study included 20 patients
      (median age 55 years) who had surgery for recurrent saphenofemoral incompetence.
      MATERIALS AND METHODS: A total of 28 legs had groin re-exploration with repeat
      flush saphenofemoral ligation. The venous tissue block from the saphenofemoral
      region (including the proximal thigh varicosity) was excised and orientated for
      histological analysis. Evidence of neovascularisation was sought using routine
      histological sections and S100 immunohistochemistry. RESULTS: At operation, thin
      walled, serpentine neovascular veins were detected clinically as the principal
      cause of recurrence in 19 groins. In five groins recurrence was due to a residual
      missed vein at the saphenofemoral junction, and in four recurrence was caused by
      cross groin collaterals. On histological sections, evidence of neovascularisation
      was present in 27 of 28 groins. In eight it co-existed with the veins missed at
      the original operation but it was the sole identified cause of recurrent
      saphenofemoral incompetence in 19 (68%) groins. CONCLUSIONS: Neovascularisation
      was the principal cause of recurrent saphenofemoral incompetence in this series.

PMID- 9633497
TI  - Physical and mechanical properties of ePTFE stretch vascular grafts determined by
      time-resolved scanning acoustic microscopy.
AB  - OBJECTIVES: Determination of physical and mechanical characteristics and
      properties of thin-walled (0.39 mm) expanded polytetrafluoroethylene stretch
      vascular prostheses by time-resolved scanning acoustic microscopy (TR-SAM).
      MATERIALS AND METHODS: Samples of Stretch Gore-Tex were mounted on
      polymethylmethaacrylate substrate, and ethyl alcohol was used as acoustic
      couplant. A 10 MHz ultrasound transducer mounted on a SAM50 scanning acoustic
      microscope generated short, pulsed sound waves. Reflected signals were used for
      imaging and for computer analysis of time resolved wave forms acquired by a
      digital sampling oscilloscope to calculate physical and mechanical
      characteristics of the material. RESULTS: Graft wall thickness: 0.395
      (0.352/0.401) mm; graft wall sound wave penetration velocity: 1111 (1083/1129) ms
      1; acoustic impedance: 3.685 (2.975/4.370) 10(6) kg m-3s-1; attenuation
      coefficient: 0.144 (0.096/0.229) dB mm-1 MHz-1; material density: 3360
      (2712/3982) kg m-3; elastic stiffness: 4.06 (3.35/4.83) GPa (median and (25/75)
      percentiles; n = 8 samples, 10 measurements spaced 100 microns apart in each
      sample). CONCLUSIONS: TR-SAM can effectively quantify ePTFE graft wall
      properties, and new data on graft properties have been provided. The acoustic
      impedance and elastic stiffness of the ePTFE graft wall are 2.2 and 1.6 times
      higher, respectively, than in human coronary arteries, and it is highly
      reflective of ultrasound.

PMID- 9633498
TI  - Early carotid endarterectomy after non-disabling ischaemic stroke: adequate
      therapeutical option in selected patients.
AB  - OBJECTIVE: To evaluate neurological outcome and long-term results of early
      carotid endarterectomy (CEA) after non-disabling stroke. MATERIALS: Retrospective
      study between 1980 and 1995 of 56 patients undergoing CEA within 4 weeks of a
      transient (n = 15) or a permanent non-disabling (n = 41) ischaemic stroke.
      METHODS: Analyses of preoperative cerebral CT imaging, neurological outcome (mod.
      Rankin-scale) and long-term results (life-table analyses according to Kaplan
      Meier). RESULTS: Incidence of early CEA increased from 1.7% (27 out of 1636) in
      the period 1980-1993 to 7.8% (29 out of 374) between 1994 and 1995. CEA was
      indicated after a neurological plateau phase was established (median interval 14
      days). Fifty-seven per cent of the CEA patients had a minor ischaemic infarction
      (area < 2 cm), 18% showed a large territorial ischaemic infarction (area 2-5 cm)
      in cerebral CT imaging. Two patients deteriorated postoperatively (minor stroke
      rate 4%) but no major stroke or death occurred. Life-table probability of stroke
      free survival (mean follow-up 42.7 months) was 94%, 90% and 84%, respectively,
      after 1, 2 and 5 years. Kaplan-Meier survival rates were 96%, 91% and 86% after
      1, 2 and 5 years. CONCLUSIONS: Early CEA after non-disabling stroke is a safe
      procedure in selected patients.

PMID- 9633499
TI  - A seasonal variation in the incidence of ruptured abdominal aortic aneurysms.
AB  - OBJECTIVE: To discover whether there is a seasonal variation in the incidence of
      rupture of abdominal aortic aneurysms. DESIGN: Deaths per month due to rupture of
      abdominal aortic aneurysm were analysed retrospectively using a cosinor
      regression model. SETTING: England and Wales. SUBJECTS: 19,599 patients who died
      from rupture of abdominal aortic aneurysm between January 1991 and December 1995
      according to death certification data. INTERVENTIONS: None. RESULTS: A seasonal
      variation in the incidence of rupture of abdominal aortic aneurysm occurs, with a
      peak in winter (p = 0.003). The ratio of rupture of abdominal aortic aneurysm in
      males and females decreased from more than 12 to 1 below age 60 years to less
      than 5 to 1 over age 80 years. CONCLUSIONS: There is a seasonal variation in the
      incidence of recorded deaths from abdominal aortic aneurysm in England and Wales,
      with a peak of deaths in the cold winter months. The underlying cause is unknown,
      but hypertension and tobacco smoking are predisposing factors to aortic aneurysm
      rupture. Exposure to tobacco smoke is known to be greater indoors in cold weather
      and there is a winter peak of blood pressure in hypertensive patients.

PMID- 9633500
TI  - Economising vein-graft surveillance programs.
AB  - OBJECTIVES: To investigate the effectiveness of two alternative vein-graft
      surveillance strategies. In the first strategy surveillance was restricted to
      patients with a possible higher risk of significant stenosis development, i.e.,
      those with a moderate stenosis identified early after the operation. In the
      second strategy the effects of reducing the number of duplex tests per patient
      was examined. PATIENTS AND METHODS: In a prospective study in three vascular
      surgical departments 300 patients (300 femoropopliteal or distal grafts)
      underwent duplex surveillance during the first year after the operation. The
      duplex-derived PSV-ratio was considered to represent the degree of stenosis.
      Arteriographic confirmation of suspected stenoses was routinely obtained, and
      patients without a suspected graft stenosis underwent a consented arteriogram
      during the first postoperative year. The decision to perform a graft revision was
      taken on the basis of an arteriographic stenosis of at least 70% diameter
      reduction. In the first strategy graft categories were defined on the basis of
      the first postoperative duplex examination: grafts with a PSV-ratio < 1.5, grafts
      with a PSV-ratio < 1.5-2.0, grafts with a PSV-ratio of 2.0-2.5, grafts with PSV
      ratios 2.5-3.0, and grafts with PSV-ratios > 3.0. The primary patency rate at 12
      months was compared for these categories. In the second alternative strategy the
      number of examinations and the percentage of event causing de novo stenoses were
      analysed per surveillance interval. RESULTS: The presence of moderate
      abnormalities at the initial duplex scan did not identify patients with a high
      risk of an event, as initial PSV-ratios of 1.5-2.0 and 2.0-2.5 (early mild
      moderate lesions) had comparable 12-month primary patencies to patients with a
      PSV-ratio < 1.5 (completely normal grafts): (63%, 73%, and 71%, respectively).
      The interval incidence of event causing de novo stenoses was 8% of the total
      number of duplex tests performed at 3 months, and 8% at 6 months after the
      operation. In patients who had no previous intervention for stenosis and had a
      normal bypass during the first 6 months postoperatively, a sharp drop in this
      incidence was seen at 9 and 12 months, with event causing de novo stenoses
      observed in only 2% and 1% of all duplex tests. CONCLUSIONS: All patients should
      be included in a surveillance program, as the presence of a normal vein graft at
      the first duplex examination does not rule out the subsequent development of
      graft stenosis. The duration of the surveillance period may be restricted to the
      first 6 months after operation in patients who have a normal bypass during that
      time period, as only few stenoses will be missed by this policy.

PMID- 9633501
TI  - Management of iliac occlusions with a new self-expanding endovascular stent.
AB  - OBJECTIVES: To determine the patency and acceptability of the Memotherm
      endovascular stent in the treatment of iliac arterial occlusions. MATERIALS AND
      METHODS: Twenty-two patients (12 males and 10 females) underwent stenting of
      iliac occlusions of the aortoiliac bifurcation, the common iliac artery and the
      external iliac artery. All patients were reassessed at 3, 6 and 12 month
      intervals and then yearly to evaluate their symptoms and Doppler pressure
      measurements. Comparison was made with results from other studies treating iliac
      occlusions by angioplasty alone or combined with stenting. RESULTS: Out of 22
      patients, 21 had an immediate and sustained improvement over the whole of the
      follow-up period. The Ankle-brachial Index (ABI) increased from a mean value of
      0.49 to 0.81 3-months postprocedure and improved to 0.85 at 12 months (paired t
      test p < 0.001). At 6 and 12 months the stent patency remained at 95.5%, which
      compares favourably with other studies. There were four minor and one major
      complication associated with the stenting procedure. CONCLUSIONS: The Memothern
      self-expanding stent is a useful, safe and effective device suitable for the
      majority of iliac occlusions. Further long-term evaluation is warranted to
      confirm its advantages over open surgery.

PMID- 9633502
TI  - Venous allografts prepared from stripped long saphenous vein. Is there a need for
      antibiotic sterilisation?
AB  - AIM: Can useful lengths of vein be retrieved from varicose vein stripping
      procedures; is it necessary to sterilise this tissue prior to use as vein
      allografts? METHOD: Stripped long saphenous vein was retrieved at operation. Vein
      samples were cultured using direct plate inoculation and enrichment culture.
      Further samples were immersed in two low concentration antibiotic solutions and
      recultured. Smooth muscle viability was assessed after antibiotic immersion and
      storage by cryopreservation. RESULTS: High quality vein could be retrieved by
      vein stripping. Vein segments grew skin commensals on enrichment culture despite
      negative cultures with standard media plate inoculation (Chi-squared = 53.34 1
      d.f. p < 0.001). Low concentration antibiotic solutions sterilised processed
      vein. Smooth muscle cell viability was reduced by cryopreservation, Mann-Whitney
      p = 0.008 (control 98% S.E. 0.93 vs. cryopreserved 64% S.E. 6.58), but prior
      exposure to antibiotics did not compound this effect. CONCLUSION: Useful lengths
      of vein grafts can be retrieved from varicose vein stripping procedures. Venous
      segments are frequently contaminated by skin commensals. Enrichment culture is
      required to detect contamination. Low concentration antibiotics sterilise venous
      tissue without affecting smooth muscle cell viability.

PMID- 9633503
TI  - Polytetrafluoroethylene (PTFE) femorodistal grafts with a distal vein cuff for
      critical ischaemia.
AB  - OBJECTIVE: To analyse the results of PTFE femorodistal bypass grafts using a
      distal anastomotic vein cuff in the treatment of critical ischaemia. DESIGN:
      Prospective study of consecutive patients under the care of a single Vascular
      Surgeon. SETTING: A dedicated Vascular Surgical Unit in a University teaching
      hospital. SUBJECTS: Fifty-one consecutive femorodistal PTFE grafts were performed
      on 50 patients (median 74 years, range 58-94 years, 25 men; median ankle:brachial
      index 0.4). In 28 (55%) a common ostium arteriovenous fistula (AVF) was fashioned
      at the distal anastomosis. RESULTS: The 30-day postoperative mortality was 8%,
      with 10 (21%) major complications. The 1 and 2 year primary patency was 64% and
      51%, respectively, with corresponding limb salvage rates of 85% and 80%. The
      presence of an AVF did not significantly affect graft patency or patient
      survival, but appeared to hinder limb salvage. The latter effect may be due to
      bias in patient selection. CONCLUSION: PTFE femorodistal grafts with a distal
      vein cuff are a suitable alternative to autogenous saphenous vein in distal
      reconstructions for critical ischaemia. No conclusions can be made about the
      efficacy of an AVF in this context.

PMID- 9633504
TI  - Primary repair of ruptured aortitis.

PMID- 9633505
TI  - Cystic adventitial disease.

PMID- 9633506
TI  - A superficial femoral artery aneurysm in a patient with Marfan's syndrome.

PMID- 9633507
TI  - Superficial femoral artery mycotic aneurysm following appendicectomy.

PMID- 9633508
TI  - Sequential progression of the differentiation program by bone morphogenetic
      protein-2 in chondrogenic cell line ATDC5.
AB  - During embryonic development of long bones, chondroprogenitor cells exhibit the
      transitions of phenotype, i.e., from type I collagen-expressing cells to type II
      collagen-expressing chondrocytes through cellular condensation (early-phase
      differentiation) and then to type X collagen-expressing mineralizing chondrocytes
      (late-phase differentiation). The chondrogenic cell line ATDC5 displays the
      sequential transitions of phenotype in a synchronous manner in vitro. Taking
      advantage of the sequential differentiation, the effects of growth factors were
      evaluated at each differentiation step of ATDC5 cells. Among the factors
      examined, bone morphogenetic protein-2 (BMP-2) specifically stimulated a
      progression of the early-phase differentiation. Rounded chondrocytic cells were
      formed all over the culture plates by skipping out a cellular condensation stage.
      Fibroblast growth factor-2 stimulated growth of undifferentiated ATDC5 cells, but
      failed to stimulate overt chondrogenesis. The proliferation of differentiated
      cells ceased as cartilage nodules became maturated. At this stage, BMP-2 markedly
      up-regulated expression of type X collagen mRNA (a 9.1-fold increase) and
      alkaline phosphatase mRNA (a 7.5-fold increase) within 48 h. On the other hand,
      it down-regulated expression of type II collagen and parathyroid hormone
      (PTH)/PTH-related peptide (PTHrP) receptor mRNAs, markers of the early
      differentiation. BMP-2 stimulated the formation of calcified matrix, an end
      product of terminally differentiated chondrocytes. These results indicated that
      BMP stimulated the sequential progression of early- and late-phase
      differentiation of ATDC5 cells.

PMID- 9633509
TI  - PD 98059 prevents establishment of the spindle assembly checkpoint and inhibits
      the G2-M transition in meiotic but not mitotic cell cycles in Xenopus.
AB  - Most chemotherapeutic agents block DNA replication, damage DNA, or interfere with
      chromosome segregation. The existence of checkpoints, which monitor these events,
      indicates that mechanisms exist to avoid death when essential cellular events are
      inhibited. A molecular understanding of cellular checkpoints should therefore
      provide opportunities for the development of inhibitors of checkpoint controls
      which may increase the potency of chemotherapeutic drugs by inducing catastrophic
      cell cycle progression. The molecular dissection of cell cycle arrest points is
      facilitated in the Xenopus egg/oocyte system, in which cell-free systems retain
      both S/M and spindle assembly checkpoints. Members of the MAP kinase family have
      been shown to play a role in the induction of G2 to M transition during oocyte
      maturation and have been implicated in the maintenance of either cytostatic
      factor- or spindle assembly checkpoint-induced M-phase arrest. Here, we have
      examined the effects of the inhibitor of MAP kinase kinase activation, PD 98059,
      on cell cycle progression in Xenopus oocytes and in cell-free extracts. This
      inhibitor is highly specific for the kinase which activates the classical p42/p44
      MAP kinase, having no effect on upstream activators of stress-activated protein
      kinases. We have found that PD 98059 inhibits oocyte maturation, consistent with
      a role for p42 MAP kinase as a rate-limiting component in the induction of
      meiosis, but had no effect on the timing of G2-M transition in cell-free extracts
      indicating that, unlike meiosis, p42 MAP kinase activation is not limiting for
      normal mitotic M phase entry. However, we found that cytostatic factor-induced
      metaphase arrest, as well as the spindle assembly checkpoint, were both abolished
      in the presence of the drug. These results demonstrate that p42 MAP kinase, and
      not some other member of the MAP kinase family, is responsible for both CSF- and
      checkpoint-induced metaphase arrest and suggest that PD 98059 and similar agents
      may have considerable therapeutic potential for the potentiation of
      chemotherapeutic regimes.

PMID- 9633510
TI  - Myristoyl-coA:protein N-myristoyltransferase from bovine cardiac muscle:
      molecular cloning, kinetic analysis, and in vitro proteolytic cleavage by m
      calpain.
AB  - Myristoyl-CoA:protein N-myristoyltransferase (NMT) catalyzes the attachment of
      myristate onto the amino terminal glycine residue of select polypeptides. Cardiac
      tissue expresses high levels of cAMP-dependent protein kinase whose catalytic
      subunit is myristoylated; however, cardiac muscle extracts were found to contain
      low NMT activities. Northern blot analysis of bovine heart poly(A)+ RNA probed
      with bovine spleen NMT cDNA revealed a 1.7-kb mRNA. Western blot analysis of
      cardiac muscle extracts with human NMT antibody indicated a prominent
      immunoreactive band with a molecular mass of 50 kDa. The expression of mRNA and
      protein levels in cardiac muscle is not correlated with NMT activities,
      suggesting the presence of regulators of the enzyme activity. We have isolated
      the cDNA encoding bovine cardiac muscle NMT (cNMT) by reverse transcription
      polymerase chain reaction. The single long open reading frame of 1248 bp of
      bovine cNMT specifies a protein of 416 amino acids with a predicted mass of
      46,686 Da. The cDNA clone expressed in Escherichia coli resulted in the
      production of functionally active 50-kDa NMT. Ultrastructural and
      immunolocalization of NMT utilizing the immunogold labeling technique
      demonstrated cytoplasmic distribution with occasional mitochondrial and
      myofilaments localization of the NMT antibody. Cardiac muscle NMT has a higher
      affinity for myristoyl-CoA than toward palmitoyl-CoA. Substrate specificity
      indicated that cNMT has a higher affinity toward pp60src and M2 gene segment of
      reovirus type 3-derived peptide substrates than toward cAMP-dependent protein
      kinase-derived peptide. Primary translational product of cNMT sequence contained
      several regions rich in proline, glutamic acid, serine, and threonine, which are
      known as "PEST" regions. PEST-FIND analysis of the amino acid sequences indicated
      eight PEST regions were present in the cNMT. These PEST regions are suggested to
      be recognized by specific proteases, particularly Ca(2+)-dependent neutral
      proteases, calpains, which are responsible for the degradation of PEST-containing
      proteins. We have demonstrated the abolishment of NMT activity and NMT protein
      degradation in vitro by m-calpain. The proteolysis of cNMT by m-calpain and the
      abolishment of NMT activity was prevented by the calpain inhibitor, calpastatin.
      These observations indicate that calpains may regulate NMT activity.

PMID- 9633511
TI  - Entactin-2: a new member of basement membrane protein with high homology to
      entactin/nidogen.
AB  - Using the new signal sequence trap (SST) method, we isolated several clones
      encoding secreted and transmembrane proteins from KUSA cells, a murine osteoblast
      like cell line. One isolated novel clone, termed entactin-2, exhibited a high
      similarity to mouse entactin/nidogen, a basement membrane protein. Although
      deduction of the amino acid sequence of entactin-2 revealed only 27.4% homology
      to entactin, many structural similarities were seen between both proteins.
      Entactin-2 contains five EGF-like and two thyroglobulin-like motifs, which are
      both cysteine-rich. Comparison of both proteins clearly revealed that entactin-2
      also contains related domain structures. The rod-like domain of entactin-2,
      containing the RGD integrin recognition sequence, fused to glutathione-S
      transferase (GST), revealed a cell surface-binding activity similar to that of
      entactin. In addition, the tissue distribution of entactin-2 mRNA resembled that
      of entactin. Furthermore, mRNA expression of both genes decreased as osteoblastic
      differentiation progressed. These results suggest that entactin-2 is a member of
      the entactin gene family, may have entactin-related functions, and might act as a
      basement membrane component.

PMID- 9633512
TI  - Major changes in chromatin condensation suggest the presence of an apoptotic
      pathway in plant cells.
AB  - A large decrease in fluorescence intensity of propidium iodide (PI)-stained
      nuclei is observed during senescence of plant cells. The phenomenon reflects a
      decrease in accessibility of DNA to this fluorochrome and is a consequence of
      chromatin condensation. This decrease is substantially greater than usually found
      in animal nuclei whose chromatin undergoes condensation, e.g., during
      differentiation or quiescence. Chromatin condensation was confirmed by analyses
      of (i) DNA accessibility to DNase I, (ii) histone disassociation induced by HCl,
      (iii) saturation of binding sites by the PI fluorochrome (iv), and (v) visual
      inspection by fluorescence and confocal microscopy. The extent of changes
      revealed by these assays was used to map progressive changes in chromatin
      condensation which allowed us to identify different stages in an apoptosis-like
      pathway in plants. The initial step of chromatin condensation which occurred
      prior to endonucleolytic DNA degradation was detected by fluorescence and
      confocal microscopy and confirmed by a variety of assays employing flow
      cytometry. The initial chromatin condensation appears to be a reversible step in
      the early stage of apoptosis. The loss of reversibility of chromatin condensation
      observed subsequently may be a critical point in the cascade of apoptotic events,
      leading to further irreversible changes during apoptosis in plants.

PMID- 9633513
TI  - Embryonic stem cells and embryoid bodies express lymphocyte costimulatory
      molecules.
AB  - Despite the importance of the costimulatory proteins B7-1 (CD80), B7-2 (CD86),
      and their counterreceptors CD28 and CTLA-4 (CD154) in the regulation of T cell
      proliferation in the adult immunological system, the initial appearance of these
      proteins during embryonic development has not been investigated. Using in vitro
      cultures of undifferentiated mouse embryonic stem (ES) cells and differentiating
      embryoid bodies as a model of very early embryonic development, we examined these
      cells for the presence of mRNA and protein corresponding to the B7 and CD28
      families of costimulatory molecules. By flow cytometry, a stochastically
      regulated subpopulation of B7-1+ cells comprising 33% of total cells was detected
      in ES cell cultures, while negligible staining was found for B7-2, CTLA-4, and
      CD28. When ES cells were differentiated into embryoid bodies for 12 days, a CD45+
      subpopulation of embryoid body cells were found to stain positively for B7-1, B7
      2, and CD28. RT-PCR confirmed cell staining data by revealing amplification
      products corresponding to B7-1, B7-2, and CD28 in corresponding samples. Very low
      levels of CTLA-4 amplification products were found in all samples; however,
      surface staining of CTLA-4 was never detected. The functional capacity of ES cell
      B7-1 to bind its ligand was verified by the ability of the soluble fusion protein
      CTLA-4-Ig to bind ES cells and the ability of this reagent to block anti-B7-1
      antibody binding in cell based competition assays. These results demonstrate that
      expression of costimulatory molecules arises very early during in vitro
      development and suggests that the early embryonic environment may utilize
      cellular signaling systems analogous to those seen in the immune system.

PMID- 9633514
TI  - S- and G2-phase cell cycle arrests and apoptosis induced by ganciclovir in murine
      melanoma cells transduced with herpes simplex virus thymidine kinase.
AB  - Mechanism of cell killing by transfer of Herpes simplex virus type-1 thymidine
      kinase (HSVtk) and subsequent ganciclovir (GCV) treatment was examined in B16F10
      murine melanoma model. While parental B16F10 melanoma cells were resistant to GCV
      at 100 microM or higher, HSVtk-transduced B16F10 melanoma cell clones became
      susceptible to GCV with IC50 of 0.1 to 0.3 microM. By means of various parameters
      including characteristic morphological changes, in situ DNA end-labeling, DNA
      ladder pattern, flow cytometric detection of sub-G1 DNA content, and annexin V
      binding of inverted cell surface phosphatidylserine, apoptosis was shown to be
      associated with the cell killing of ganciclovir on HSVtk-transduced melanoma
      B16F10 cells. Kinetic analysis showed that the signs of apoptosis were observed
      not until 60 h of continued GCV treatment and preceded first by a rise in p53
      protein level in 12 h and then by S-phase/G2-phase cell cycle arrest associated
      with corresponding increases in the level of cyclin B1 protein but no apparent
      change in protein level of Bax or Cdc2. These results suggest that apoptosis
      occurred as a result of ganciclovir-induced cell cycle arrests rather than direct
      chemical effect on HSVtk-transduced B16F10 melanoma cells.

PMID- 9633515
TI  - The human papillomavirus type 16 E5-protein modulates ligand-dependent activation
      of the EGF receptor family in the human epithelial cell line HaCaT.
AB  - The E5 open reading frame of the human papillomavirus type 16 encodes a
      transmembrane protein associated with the Golgi, ER, and plasma membranes. We
      have analyzed the effect of E5 expression on the activation of the EGF receptor
      family. We find that expression of the E5-protein strongly enhances EGFR
      activation in a ligand-dependent manner. This activation takes place immediately
      after addition of ligand, demonstrating that increased tyrosine phosphorylation
      cannot solely be due to an impaired downregulation of the receptors. Furthermore,
      this activation is not a result of impaired activity of EGFR-specific phosphatase
      through the E5-protein, as demonstrated by using inhibitors specifically blocking
      EGFR activation. In addition, treatment with EGF results in an enhanced
      activation of the ErbB2 receptor in E5-expressing cells. This superactivation
      must be a result of heterodimer formation between EGFR and ErbB2, since EGF is
      not a ligand for ErbB2. Finally, treatment of E5-expressing cells with HB-EGF
      shows no increased phosphorylation of the ErbB4 receptor, suggesting a specific
      effect of E5 on the activation of the different members of the EGFR family.

PMID- 9633516
TI  - KH domain integrity is required for wild-type localization of Sam68.
AB  - The protein Sam68 (Src-associated in mitosis, 68 kDa) has been found to bind to
      SH2 and to SH3 domain-containing proteins and to RNA. Although its protein
      protein interactions implicate Sam68 in cell signaling, the significance of its
      RNA binding remains obscure. In most cells, Sam68 shows diffuse nucleoplasmic
      staining. Upon treatment with transcription inhibitors, however, Sam68 localize
      into punctate nuclear structures. Mutant forms of mouse Sam68 were overexpressed
      in human cells to test the importance of the KH domain, which is required for RNA
      binding, in the intracellular localization of Sam68. A small deletion within the
      KH domain (delta 206-218) or point mutation I184N had no effect upon the
      localization of overexpressed Sam68. Sam68 that contained a deletion of the
      entire KH domain (delta KH, delta 157-256) or point mutation G178E, however,
      localized to distinct nuclear spots. Furthermore, delta KH Sam68, unlike wild
      type Sam68 and several other mutant Sam68 proteins, did not relocalize upon
      poliovirus infection and caused the normally cytoplasmic viral polymerase to
      localize to the nuclear spots. Thus both ongoing transcription and an intact KH
      domain are crucial determinants of the dynamic intracellular localization of
      Sam68.

PMID- 9633517
TI  - Inactivation of p53 in a human ovarian cancer cell line increases the sensitivity
      to paclitaxel by inducing G2/M arrest and apoptosis.
AB  - Paclitaxel-induced cytotoxicity, cell cycle perturbation, and apoptosis were
      determined in a human ovarian cancer cell line expressing wt p53 (A2780) and in a
      subclone (A2780/E6) obtained upon transfection with the product of the E6 gene of
      the human papilloma virus HPV16. The inactivation of wt p53 in A2780/E6 was
      verified by measuring the inability of the clone to induce p53 and p21 expression
      after paclitaxel treatment. The p53-negative clone (A2780/E6) was approximately
      50-fold more sensitive to paclitaxel than wt p53-expressing A2780 cells. This
      increased sensitivity was related to the ability of paclitaxel to induce a strong
      arrest of cells in the G2/M phase of the cell cycle in A2780/E6 but not in A2780
      cells. This different cell cycle arrest was accompanied by increased frequency of
      paclitaxel-induced p53-independent apoptosis. Initial studies on proteases
      activation tend to exclude a direct role of ICE and CPP32 in the induction of
      apoptosis in these cells and show a paclitaxel-dependent increase in FLICE
      levels, whose biological relevance is however at present not defined.

PMID- 9633518
TI  - Oxidative stress leads to a rapid alteration of transferrin receptor
      intravesicular trafficking.
AB  - Several studies have demonstrated that perturbations of intracellular oxidative
      balance play a key role in numerous physiological as well as pathological
      conditions leading to various morbidity states. In previous studies we have shown
      that the free radical inducer menadione rapidly and specifically downmodulates
      the membrane transferrin receptor (TfR) by blocking receptor recycling. This
      modulation is due to receptor redistribution and not to receptor loss. Here we
      show that other oxidant compounds, such as hydrogen peroxide, also induce a rapid
      downmodulation of membrane TfR and that pretreatment of cells with the
      antioxidant, thiol supplier, N-acetylcysteine inhibits the downmodulation of
      these receptors elicited by either menadione or hydrogen peroxide. This
      observation suggests that intracellular thiol redox status may be a critical
      determinant of TfR downmodulation induced by oxidative stress. Furthermore,
      immunocytochemical results show that, in menadione-treated cells, TfRs are
      associated with the Golgi complex, where normally only 20% of total cellular TfRs
      is found and is mainly detected in the cytoplasm as scattered punctuations.
      Accordingly, menadione and hydrogen peroxide also elicited a downmodulation of
      low density lipoprotein receptor (LDLR) which mediates, like TfR, the transport
      of nutrients to the cell and is endocytosed through clathrin-coated pits.
      Finally, experiments carried out using okadaic acid, an inhibitor of
      phosphatases, suggest that H2O2 and menadione downmodulate surface TfR via
      different biochemical pathways. Taken together these results suggest the
      existence of a potentially important protective mechanism through which iron
      uptake is prevented in oxidatively imbalanced cells. Iron uptake can in fact give
      rise to the formation of highly toxic hydroxyl radicals reacting with hydrogen
      peroxide and leading to cytotoxicity. Downmodulation of surface TfR may thus
      represent the physiological control mechanism for reducing iron uptake in diverse
      pathological conditions including hypoxia-reperfusion injury, acquired
      immunodeficiency syndrome, and aging.

PMID- 9633519
TI  - Disruption of the lama2 gene in embryonic stem cells: laminin alpha 2 is
      necessary for sustenance of mature muscle cells.
AB  - Mutations in the gene coding for the alpha 2 chain of laminin-2 and -4 (merosin)
      cause a severe form of congenital muscular dystrophy in humans and mice. To
      establish a defined model for in vitro and in vivo studies of the role of laminin
      alpha 2/merosin in development and cell and tissue function, we generated several
      lines of mutant embryonic stem (ES) cell with disruption of the laminin alpha 2
      chain gene. We find that homozygous mutant ES cells differentiate normally in
      vitro, giving rise to cardiomyocytes, myotubes, and smooth muscle cells in
      addition to many other cell types. However, the myotubes that are formed are
      unstable. They detach, collapse, and degenerate, a process which is initiated at
      the appearance of the mature, contractile phenotype of the cells. We propose that
      the detachment and death of contracting myotubes in vitro has its counterpart in
      vivo and that contraction-induced myofiber damage, along with the lack of
      survival cues provided by laminin alpha 2/merosin, is a significant contribution
      to muscle degeneration in merosin-deficient muscular dystrophy.

PMID- 9633520
TI  - FR901228, a potent antitumor antibiotic, is a novel histone deacetylase
      inhibitor.
AB  - Screening for microbial metabolites that induce transcriptional activation of the
      SV40 promoter resulted in the identification of two known compounds, FR901228 and
      trichostatin A (TSA). FR901228 is a potent antitumor drug that is currently under
      clinical investigation. TSA is a specific inhibitor of histone deacetylase.
      Despite structural unrelatedness, both FR901228 and TSA greatly enhanced the
      transcriptional activity of the SV40 promoter in an enhancer-dependent manner.
      The effects of FR901228 on the cell cycle, chromatin structure, and histone
      acetylation were examined and compared with those of TSA. Both compounds caused
      arrest of the cell cycle at both G1 and G2/M phases and induction of
      internucleosomal breakdown of chromatin. FR901228, like TSA, inhibited
      intracellular histone deacetylase activity, as a result of which marked amounts
      of acetylated histone species accumulated. FR901228 is therefore a new type of
      histone deacetylase inhibitor, whose chemical structure is unrelated to known
      inhibitors such as trichostatins and trapoxins.

PMID- 9633521
TI  - Antisense wnt-5a mimics wnt-1-mediated C57MG mammary epithelial cell
      transformation.
AB  - The disruption of the normal expression of wnt-5a in cell lines and in tumors is
      becoming increasingly recognized as important in cell transformation and
      tumorigenesis. For example, in endometrial cancer wnt-5a is downregulated
      compared to normal tissue. Our laboratory has recently found that the ectopic
      expression of wnt-5a in human RCC23 renal carcinoma cells missing wnt-5a gene
      expression suppresses in vitro cell growth and telomerase enzyme activity.
      Furthermore, ectopic wnt-5a in MC-T16 uroepithelial cancer cells missing the
      region of chromosome 3p where wnt-5a has been mapped reverts uroepithelial cell
      tumorigenesis in athymic nude mice. These studies were based upon the previous
      finding that wnt-1 and wnt-2 transform C57MG mammary epithelial cells by
      downregulating the endogenous expression of wnt-5a. We now report that
      transfecting C57MG cells with a mammalian expression vector carrying antisense
      wnt-5a results in a cell phenotype that mimics cell transformation by ectopic wnt
      1 or wnt-2. Correspondingly, wnt-1-transformed cells are partially reverted in
      the presence of ectopic wnt-5a. We conclude from this that wnt-5a is an important
      regulator of cell growth and differentiation and its loss of expression leads to
      cell transformation.

PMID- 9633522
TI  - Effect of type II collagen in chondrocyte response to TGF-beta 1 regulation.
AB  - The in vivo role of the extracellular matrix and the manner in which it
      interfaces with soluble regulators remains unknown. This study reports the
      modulation by extracellular type II collagen of TGF-beta 1-stimulated DNA
      synthesis, proteoglycan synthesis, and mRNA expression for alpha 1(II)
      procollagen and aggrecan core protein in the adult articular chondrocyte. Bovine
      chondrocytes were isolated and resuspended in alginate beads which contained
      increasing amounts of type II collagen from 0 to 1.5% (w/v). Cultures were
      maintained for 7 days in basal, DMEM, TGF-beta 1 (10 ng/ml), or FBS (10%)
      supplemented medium. DNA and proteoglycan synthesis were determined by
      radiotracer incorporation. The relative amounts of mRNA were analyzed by Northern
      blot analysis. Exogenous collagen increased DNA synthesis in all culture
      conditions beginning at concentrations of 0.75% (w/v). We observed that
      extracellular type II collagen augments both TGF-beta 1 stimulated increases of
      aggrecan gene expression up to 400% and alpha 1(II) procollagen gene expression
      up to 180% in a dose-dependent fashion. This is distinct from cultures which were
      either basal or FBS supplemented medium which lacked a dose-dependent change in
      aggrecan gene expression and demonstrated a decrease in alpha 1(II) procollagen
      gene expression. Exogenous collagen above 0.75% (w/v) increased proteoglycan
      synthesis significantly in FBS and TGF-beta 1-stimulated cultures but not in
      basal cultures. We have demonstrated that the alterations in gene expression that
      occur in response to TGF-beta 1 are modulated by extracellular type II collagen.
      This modulation is possible through both transcriptional and posttranscriptional
      regulatory mechanisms.

PMID- 9633523
TI  - The conventional transforming growth factor-beta (TGF-beta) receptor type I is
      not required for TGF-beta 1 signaling in a human prostate cancer cell line,
      LNCaP.
AB  - LNCaP is an androgen-responsive human prostate cancer cell line that has a
      defective gene for ALK-5, the conventional TGF-beta receptor type I. Yet, these
      cells respond to exogenous TGF-beta 1 under appropriate concentrations of
      dihydrotestosterone (DHT). Because a heteromeric complex composed of type I and
      type II receptor is required for TGF-beta signaling, the expression of these
      receptors was investigated in LNCaP cells at following concentrations of DHT-0,
      0.1, and 100 nM. These concentrations were selected because they represent the
      zero DHT control in which LNCaP cells are not sensitive to TGF-beta 1, the
      proliferative dose of DHT in which these cells are sensitive to exogenous TGF
      beta 1, and the growth-arrest dose of DHT in which LNCaP exhibits signs of TGF
      beta signaling but are insensitive to exogenous TGF-beta 1, respectively. Results
      of Western blot analysis showed that LNCaP cells express an increased level of
      type II receptor at 0.1 nM DHT, the TGF-beta 1-sensitive dose. However, results
      of competitive quantitative RT-PCR demonstrated that DHT did not significantly
      change the level of type II receptor mRNA, suggesting that DHT modulates the
      level of type II receptor at the posttranscriptional level. In contrast, ALK-5
      was not detected in these cells by either Western blot analysis or RT-PCR at all
      concentrations of DHT used in this study. Subsequently, the expression of ALK-1, 
      2, and -4 in LNCaP cells was examined because these proteins have been shown to
      bind TGF-beta 1 in vitro. ALK-1 and -2 were detected in these cells. Further
      analysis by competitive quantitative RT-PCR and Western blot demonstrated that
      DHT did not affect the level of expression of ALK-1 and -2 in LNCaP cells. These
      observations, taken together, demonstrate that ALK-5 is not required for TGF-beta
      1 signaling and that there may be alternative mechanism(s) for TGF-beta 1 signal
      transduction in some systems.

PMID- 9633524
TI  - Differential binding characteristics and cellular inhibition by soluble VEGF
      receptors 1 and 2.
AB  - The FLT-1 and KDR genes encode transmembrane tyrosine kinases which function as
      high-affinity receptors for vascular endothelial growth factor (VEGF). We have
      used the baculovirus system to express the extracellular parts of the FLT-1
      receptor and KDR receptor in soluble form (sFLT-1 and sKDR), for in vitro binding
      and competition assays. Here, we show that the binding of VEGF165 to sKDR but not
      sFLT-1 is dependent on heparin, regardless of whether VEGF165 or sKDR is
      immobilized. Further, only sFLT-1 acts as a receptor antagonist in solution and
      sKDR can neither compete with the binding of VEGF165 to human endothelial cells
      carrying both receptors nor block VEGF165 induced mitogenicity. Soluble KDR only
      partially inhibits cell migration even at high concentrations, in contrast to
      sFLT which can almost completely block (82%) VEGF-induced cell proliferation and
      migration. Taken together these results show that the two soluble VEGF receptor
      proteins, sFLT-1 and sKDR, despite binding the same ligand, behave very
      differently when immobilized with regard to their dependence on heparin for VEGF
      binding. In solution their respective ability to function as receptor antagonists
      is also strikingly different, possibly a reflection of their different dependency
      on heparin.

PMID- 9633525
TI  - HB-GAM/pleiotrophin but not RIHB/midkine enhances chondrogenesis in micromass
      culture.
AB  - The heparin-binding growth-associated molecule HB-GAM (also named pleiotrophin)
      and the retinoic acid-induced heparin-binding protein RIHB (chicken midkine) are
      developmentally regulated proteins forming a new family of heparin-binding
      molecules with putative functions during cell growth and differentiation. A
      direct involvement of these molecules during chondrogenesis in vivo was suggested
      by their patterns of expression. The putative chondrogenic activity of these
      molecules was investigated in vitro using micromass cultures from chicken limb
      bud mesenchymal cells. Exogenous HB-GAM, not RIHB, was found to enhance
      chondrogenesis in this system. These results provide a strong incentive for
      considering and further investigating the role of this protein in the control of
      limb cartilage differentiation.

PMID- 9633526
TI  - The role of the hydrophobic domain in orienting natural signal sequences within
      the ER membrane.
AB  - The orientation of signal sequences during insertion into the endoplasmic
      reticulum membrane is largely determined by the charged residues flanking the
      apolar domain. Using recombinant and mutant proteins, also length and
      hydrophobicity of the apolar segment were shown to affect the orientation:
      translocation of the N-terminus was found to be favored by long hydrophobic
      sequences, and translocation of the C-terminus, by short ones. Here, we tested
      the physiological significance of this phenomenon by mutagenesis of the
      hydrophobic portion of two natural signals with unusual flanking charges.
      Extending the hydrophobic domain of the short, cleaved Ncyt/Cexo signal of pre
      provasopressin-neurophysin II and shortening that of the Nexo/Ccyt signal anchor
      of microsomal epoxide hydrolase resulted in a significant fraction of
      polypeptides inserting in the opposite orientation to that of the wild-type
      proteins. The topogenic contribution of the hydrophobic domain is thus important
      for the correct and uniform orientation of natural proteins and can explain the
      behavior of some of the signals with unusual flanking charges.

PMID- 9633527
TI  - Mechanisms of increased NGF production in vascular smooth muscle of the
      spontaneously hypertensive rat.
AB  - The spontaneously hypertensive rat (SHR) was developed as a genetic model of
      essential hypertension. In vivo and in vitro evidence demonstrates that vascular
      smooth muscle cells (VSMCs) from the SHR produce more nerve growth factor (NGF)
      than the normotensive Wistar-Kyoto (WKY) control strain. This increased NGF
      production is accompanied by excessive innervation of target tissues in the SHR.
      In the present study, a sensitive, competitive, quantitative, reverse
      transcriptase polymerase chain reaction (C Q RT-PCR) assay is characterized and
      used to analyze levels of NGF mRNA in cultured VSMCs derived from the SHR and WKY
      strains as well as bladder tissue. Differences in NGF secretion rates between SHR
      and WKY VSMCs were partially due to an increased stability of NGF mRNA in SHR
      VSMCs. Following treatment with platelet-derived growth factor (PDGF) and
      transforming growth factor-beta (TGF-beta 1) to elevate NGF production, the half
      life of the NGF mRNA was 104.5 +/- 18.0 min in SHR VSMCs, compared to only 36.5
      +/- 11.6 min in WKY VSMCs. Sequence analysis of the 3' untranslated region (UTR)
      revealed no strain differences in cis-acting sequences potentially involved in
      determining mRNA stability. Thus, it seems unlikely to be a 3'UTR mutation that
      prolongs mRNA lifetime. Rather, differential regulation of an RNA-binding protein
      may play a role in the abnormal NGF mRNA stability in SHR VSMCs. SHR VSMCs also
      demonstrate an increased translational efficiency of NGF protein; more NGF
      protein is synthesized per unit of NGF mRNA. The use of a C Q RT-PCR assay has
      allowed the determination that abnormal NGF mRNA stabilization as well as altered
      translational efficiency may contribute to excess NGF synthesis and progressive
      hypertension in the SHR.

PMID- 9633528
TI  - Differentiation-related pathways of 1 alpha,25-dihydroxycholecalciferol
      metabolism in human colon adenocarcinoma-derived Caco-2 cells: production of 1
      alpha,25-dihydroxy-3epi-cholecalciferol.
AB  - We used the human colon adenocarcinoma-derived cell line Caco-2, which
      spontaneously differentiates in vitro, as a model system to investigate the
      metabolism of 1 alpha,25-dihydroxycholecalciferol in colon cancer cells.
      Subconfluent proliferating and confluent differentiating cells were incubated
      with 1 microM 1 alpha,25-dihydroxycholecalciferol for a period of 24 to 48 h.
      HPLC analysis of the lipid extract of both cells and media was performed to
      isolate and identify the various metabolites of 1 alpha,25
      dihydroxycholecalciferol. Undifferentiated, highly proliferating Caco-2 cells
      metabolized 1 alpha, 25-dihydroxycholecalciferol into several side chain modified
      metabolites formed through the C-24 oxidation pathway. In contrast, no
      metabolites of the C-24 oxidation pathway were identified in differentiated Caco
      2 cells. However, differentiated cells produced significant amounts of a
      metabolite which was less polar than 1 alpha, 25-dihydroxycholecalciferol on a
      straight phase HPLC system. This metabolite was identified as 1 alpha,25
      dihydroxy-3alpha-cholecalciferol by comigration with a synthetic standard on two
      different HPLC systems and gas chromatography--mass spectrometry. Thus, we were
      able to demonstrate that the state of differentiation has a profound influence on
      1 alpha,25-dihydroxycholecalciferol metabolism in colon cancer cells.

PMID- 9633529
TI  - Repositioning of human interphase chromosomes by nucleolar dynamics in the
      reverse transformation of HT1080 fibrosarcoma cells.
AB  - An experimental system which should be valuable for studying the role of spatial
      positioning of the nuclear genome in human cell function has been developed.
      Reverse transformation of the malignant HT1080 fibrosarcoma cell line upon
      treatment with 8-chloro-cAMP results in growth inhibition, cytoskeletal
      reorganization, changes in nuclear shape and chromatin accessibility, and
      formation of prominent nucleoli. Fluorescent in situ hybridization was used to
      study DNA positioning during nuclear remodeling. Morphometric analysis of the
      hybridization sites for both repetitive sequences and "painting probes" for whole
      chromosomes indicated dispersal of acrocentric chromosomes in untreated cells and
      a highly organized central location of these ribosome gene-containing chromosomes
      in association with one or a few large nucleoli in nondividing treated cells. The
      results suggest that there was a directed movement of interphase chromosomes
      during a response which normalized a malignant cell line. These large-scale
      repositionings may serve two functions in restoring a normal transcriptional
      setup to the nucleus. First, ribosome genes are placed in the nucleolus, their
      transcriptional suborganelle. Second, nucleolar anchorings together with
      additional perinucleolar centromeric associations orient the domain shapes of
      entire chromosomes, installing gene-rich chromosomal regions into pockets of
      (accessible) DNAse I-sensitive chromatin populated by spliceosomes.

PMID- 9633530
TI  - Suppression of fibroblast growth factors 1 and 2 by antisense oligonucleotides in
      embryonic chick retinal cells in vitro inhibits neuronal differentiation and
      survival.
AB  - As retinal histogenesis proceeds there is a pronounced increase in the expression
      of fibroblast growth factor (FGF), reaching its maximum in the mature retina and
      largely in terminal differentiated retinal neurons. Recent in vivo evidence
      suggests that exogenous FGF functions as a differentiation and survival factor
      for a wide variety of cell types including CNS neurons and that endogenous FGF
      may perform similar functions. We have examined the consequences of selectively
      and independently inhibiting FGF1 or FGF2 expression using antisense
      oligonucleotides in embryonic chick retinal cells, differentiating in vitro.
      Whether FGF1 or FGF2 expression was inhibited the results were the same: a marked
      reduction in neuronal photoreceptor cells differentiation, an increase in
      programmed cell death, but no effects on cell proliferation. Even although these
      two related factors promote the same final effect on retinal cells, namely,
      neuronal differentiation and survival, their normal combined activities or levels
      appear to be important in achieving this effect. Stimulation with either
      exogenous FGF1 or FGF2 served to increase endogenous levels of both FGF1 and FGF2
      and reversed the effects of antisense blockade of either FGF1 or FGF2. Our data
      suggest that although other sources of FGF exist within the eye, the function of
      endogenous FGF in differentiating retinal neurons may be to stimulate their
      differentiation and promote their survival.

PMID- 9633531
TI  - Differential regulation of cyclooxygenases 1 and 2 by interleukin-1 beta, tumor
      necrosis factor-alpha, and transforming growth factor-beta 1 in human lung
      fibroblasts.
AB  - In the present studies we found that incubation of human lung fibroblasts with
      transforming growth factor-beta 1 (TGF-beta 1) potentiated the interleukin-1 beta
      (IL-1 beta) and/or tumor necrosis factor-alpha (TNF-alpha)-stimulated production
      of prostaglandin E2 (PGE2). Analysis of fibroblast proteins showed the induction
      of cyclooxygenase-1 (Cox-1) by TGF-beta 1 and the induction of Cox-2 by IL-1 beta
      and TNF-alpha. The levels of transcripts for Cox-1 were minimally modified by IL
      1 beta or TNF-alpha, however, they were increased by 12-fold by TGF-beta 1.
      Transcripts for Cox-2 were induced by IL-1 beta or TNF-alpha and their induction
      was potentiated by TGF-beta 1. TGF-beta 1 alone did not induce Cox-2 transcripts.
      In vitro transcription assays showed that IL-1 beta and TNF-alpha increased the
      transcription of the Cox-2 gene, whereas TGF-beta 1 had no effect. Addition of
      TGF-beta did not increase further the transcription of Cox-2 in IL-1 beta-treated
      cells, but increased the stability of the corresponding transcripts. The
      transcription rate of the Cox-1 gene was not increased by any of the cytokines
      studied. In summary, we demonstrate that the potentiation of PGE2 production by
      TGF-beta 1 in IL-1 beta and TNF-alpha-treated fibroblasts is the result of
      transcriptional stimulation of the Cox-2 gene by IL-1 beta and TNF-alpha and the
      stabilization of the resulting transcripts by TGF-beta 1.

PMID- 9633532
TI  - Type VI collagen increases cell survival and prevents anti-beta 1 integrin
      mediated apoptosis.
AB  - Cell-matrix interactions are important in the development of the avian cornea.
      Type VI collagen is present within the periocular mesenchyme prior to the
      migration of cells into the corneal stroma and is abundant in the mature stroma.
      Whether the interaction of cells with type VI collagen is essential for cellular
      survival in the cornea is not known. In the present study, we examined the
      interaction of corneal cells with type VI collagen in vitro to determine if it
      can increase cell proliferation and decrease apoptosis. In vivo analysis
      demonstrated that apoptosis occurs in the periocular region during early stages
      of avian corneal development, but in fully mature corneas apoptosis only occurs
      in the corneal epithelium and not in the stroma. In vitro analysis examined the
      importance of beta 1 integrin interactions with type VI collagen in mature
      corneal fibroblasts and the precursor cells. Using an anti-beta 1 integrin
      blocking antibody, CSAT, integrin/matrix interactions were disrupted. Results
      indicated that viability of both corneal fibroblasts and periocular mesenchyme
      cells was greater on type VI collagen than on type I collagen or BSA-blocked
      glass. In addition, less apoptosis was observed for both cell types on type VI
      collagen when beta 1 integrin--matrix interactions were disrupted. These data
      indicated that these cells require intact beta 1 interactions with type I
      collagen and with BSA-coated glass controls to remain viable. Thus, type VI
      collagen may play a role in the rescue of corneal cells from anti-beta 1 integrin
      induced apoptosis by increasing cell survival, probably via a non-beta 1 integrin
      dependent mechanism.

PMID- 9633533
TI  - Cytoplasmic localization of LIM-kinase 1 is directed by a short sequence within
      the PDZ domain.
AB  - LIM-containing protein kinase 1 (LIMK1) is a serine/threonine kinase with a
      structure composed of two LIM domains, a PDZ domain, and a protein kinase domain.
      We examined the subcellular localization of LIMK1 and its variously deleted
      mutants in HeLa cells by transfection with these cDNAs. Immunofluorescence
      analysis revealed that the full-length LIMK1 and its mutants deleted with LIM
      domain or protein kinase domain preferentially localized in the cytoplasm, while
      the mutants deleted with the PDZ domain or a 52 amino acid region (B region)
      within the PDZ domain localized mainly in the nucleus. When the normally nuclear
      cyclin A was fused with the PDZ domain or the B region of LIMK1, it was localized
      in the cytoplasm of transfected cells. The corresponding region of the PDZ domain
      of postsynaptic density protein (PSD)-95 had no such function. Additionally, the
      PDZ domain of LIMK1 had no potential to bind to the C-terminal S/TXV peptides, to
      which the PSD-95 PDZ domain can bind. Taken together these results suggest that
      the PDZ domain, particularly the B region, of LIMK1 has a specific function to
      localize the protein in the cytoplasm. When glutathione S-transferase (GST) fused
      with the PDZ domain of LIMK1 (GST-PDZ) or GST-PDZ deleted with the B region (GST
      PDZ delta B) was microinjected into the nucleus of COS cells, GST-PDZ was almost
      completely excluded from the nucleus within 30 min, whereas GST-PDZ delta B
      remained in the nucleus. These findings suggest that the B region of LIMK1
      probably has nuclear export signal activity.

PMID- 9633534
TI  - Structure-function relationships of pheromones of the ciliate Euplotes raikovi
      with mammalian growth factors: cross-reactivity between Er-1 and interleukin-2
      systems.
AB  - Diffusible protein signals of the ciliate Euplotes raikovi, denoted as
      pheromones, have functionally been linked with prototypic growth factors of
      animal cells by the demonstration that they not only induce a temporary cell
      union in mating pairs, by acting in a paracrine-like fashion, but can also bind
      to cells in autocrine fashion and promote their vegetative (mitotic)
      proliferation. It is now shown that pheromone Er-1 is capable of binding to the
      alpha and beta chains of the multimeric IL-2 receptor on mammalian cells and that
      IL-2 can, in turn, bind to the putative cell receptor of this pheromone.
      Similarities in the IL-2 and Er-1 structures support these findings and raise
      controversial implications with regard to their evolutionary significance.

PMID- 9633535
TI  - Stability of the replicative Mcm3 protein in proliferating and differentiating
      human cells.
AB  - Mcm proteins are abundant nuclear proteins involved in the regulation of genome
      replication. Previous experiments had shown that levels of Mcm-specific mRNAs
      increase at the G1/S phase transition of the cell cycle, but that the amounts of
      Mcm proteins do not change much during the cell cycle. To learn more about the
      stability of an Mcm protein we performed experiments which showed that: (i) more
      than 60% of [35S]methionine pulse-labeled Mcm3 protein appears to be degraded
      during a 24-h chase in HeLa cells; (ii) the amount of Mcm3 protein significantly
      decreases during the differentiation of HL60 cells in vitro (whereas another
      replication-initiation protein, hOrc2, remains fairly constant); and (iii)
      according to immunohistochemical staining, Mcm3 protein is present in nuclei of
      cells in the proliferating zone of human epidermal tissue, but in decreasing
      amounts in nuclei of differentiating cells of the upper cell layers. Our
      interpretation is that Mcm3 protein is no longer synthesized after initiation of
      differentiation and slowly disappears at a half-life of approximately 24 h.

PMID- 9633536
TI  - Sex steroids do not prevent amylin-induced apoptosis in human cells.
AB  - Formation of amylin-containing islet amyloid deposits may contribute to the
      progressive deterioration of beta cell function in non-insulin-dependent diabetes
      mellitus. As diabetes mellitus occurs in male, but rarely in female transgenic
      mice expressing human amylin in their pancreatic beta cells, it is of interest to
      study the influence of estradiol (E2) and testosterone (T) on amylin-induced
      cytotoxicity in human cells. The insulinoma cell line CM, thyroid epithelial
      cells (TEC) in primary culture, and nontransformed fibroblast lines were used.
      The occurrence of apoptotic cell death was assessed by nuclear labeling with
      propidium iodide. Amylin was cytotoxic on all cell types tested, but had the most
      pronounced effect on TEC and the weakest on the CM cell line. Although both E2
      and T decreased the proportion of apoptotic cells in cultures kept in the absence
      of amylin, neither of the two hormones was able to counteract amylin-induced
      cytotoxicity. beta cell death and hyperglycemia can thus presumably not be
      prevented by the neutralization of amylin effects by sex steroids.

PMID- 9633537
TI  - Estrogen treatment induces elevated expression of HMG1 in MCF-7 cells.
AB  - The high mobility group (HMG) 1 protein is a highly conserved and ubiquitous
      chromosomal protein found enriched in active chromatin. In this study, we have
      investigated the effect of estrogen on the expression of the human high mobility
      group protein HMG1 gene and found that the HMG1 mRNA level in MCF-7 cells was
      sharply increased 2.5-fold after 30 min of estrogen treatment. Under continuous
      estrogen treatment, the HMG1 mRNA level decreased to a 1.5 times that of the
      basal level at 90 min and remained at this elevated level under estrogen
      treatment for up to 24 h. These results support the recent finding by Verrier et
      al. (C.S. Verrier, 1997, Mol. Endocrinol. 11, 1009-1019) that HMG1 promotes the
      binding of the estrogen receptor to the estrogen response element and further
      reinforce our believe that HMG1 plays a significant role in estrogen-induced gene
      expression.

PMID- 9633538
TI  - Preventing the preventable. Undervalued and underfunded screening is undermining
      primary care.

PMID- 9633539
TI  - Cultural changes in healthcare.

PMID- 9633540
TI  - Cultural changes in healthcare.

PMID- 9633541
TI  - The elusive diagnosis of appendicitis.

PMID- 9633542
TI  - Update on upper gastrointestinal bleeding. Basing treatment decisions on
      patients' risk level.
AB  - Acute upper gastrointestinal bleeding is a common reason for hospitalization.
      Mortality rates range from 5% to 15%; patients with severe comorbidities and
      those with persistent or recurrent bleeding are at highest risk. Accurate
      preliminary risk assessment and resuscitation can proceed simultaneously at
      initial presentation. Risk assessment can guide treatment decisions. Early upper
      gastrointestinal endoscopy, a cornerstone of management, allows for rapid
      diagnosis, application of endoscopic therapy, and completion of risk assessment.
      Endoscopic therapy can alter the natural history of upper gastrointestinal
      bleeding by reducing rates of further bleeding and, consequently, mortality.
      Complete risk assessment of both clinical and endoscopic factors can likely
      result in shorter hospital stays and improved outcomes. Early assessment helps
      identify low-risk patients in whom discharge on the day of presentation is
      appropriate.

PMID- 9633543
TI  - Newer oral antimicrobials for resistant respiratory tract pathogens. Which show
      the most promise?
AB  - As antimicrobial resistance to tried-and-true drugs continues to build, an
      arsenal of new drugs aimed at resistant respiratory tract pathogens is needed.
      Penicillin is now ineffective against several common pathogens, including many
      pneumococcal organisms. Newer antimicrobials, including macrolides,
      cephalosporins, and fluoroquinolones, have been developed to take its place. The
      authors of this article present a progress report of the fight against
      respiratory tract infection and an assessment of the most promising newer agents
      for use against multidrug-resistant pathogens.

PMID- 9633544
TI  - Bites and stings of the arthropod kind. Treating reactions that can range from
      annoying to menacing.
AB  - Bites and stings from arthropods are largely inevitable because of the number of
      offending species and their distribution throughout our environment. Wasps, bees,
      ants, mosquitoes, gnats, chiggers, and fleas are found all across the United
      States. Thus far, Africanized honeybees are limited to southwestern states and
      fire ants to southern states. Brown recluse spiders are found most often in the
      Midwest and south central region, but the black widow spider is found in all 48
      contiguous states. The dangerous Centruroides species of scorpion live mostly in
      southern states and California. Fortunately, in most people, bites and stings
      from arthropods produce only self-limited reactions, which can usually be managed
      with cold packs, analgesics, and topical agents. In the few encounters that
      produce serious reactions, prompt diagnosis and appropriate treatment result in a
      good outcome in nearly all cases. The number of stings and bites can be reduced
      with use of a few basic avoidance and protection measures.

PMID- 9633545
TI  - Heat-related illness. Plan ahead to protect your patients.
AB  - Environmental heat illnesses range from irksome to devastating. People at
      particular risk are the elderly, the chronically mentally ill, the community
      dwelling developmentally delayed, people without social contacts, athletes, and
      those without access to air-conditioning. Because heat-related deaths are
      preventable, community-wide response to heat emergencies, together with
      individual and community education programs, could greatly decrease morbidity and
      mortality.

PMID- 9633546
TI  - Food poisoning. Causes, remedies, and prevention.
AB  - Food producers and consumers must continue to take precautions against foodborne
      diseases, and early diagnosis and appropriate treatment of these illnesses are
      essential. Food products and water can become contaminated with microorganisms
      and toxins that make people ill, and the very young, the elderly, and
      immunocompromised individuals are especially susceptible. Education of healthcare
      providers, food handlers, and the public is critical in reducing the incidence
      and spread of foodborne illness. Changes in eating habits and lifestyle and
      increased availability of both domestic and imported foods have made food hazards
      a more complex public health issue. Although most foodborne illnesses can be
      avoided by safe food handling procedures (see box on page 134), risk reduction is
      very important at every step from source to table. A concerted effort is needed
      to ensure continuing safety of the food supply in the United States while also
      assuring access to a wide variety of healthful foods. Time will tell whether
      consumers will accept irradiation of meats. If accepted, irradiation could rank
      in importance with pasteurization of milk and chlorination of water as a public
      health measure.

PMID- 9633547
TI  - Near drowning. Rescuing patients through education as well as treatment.
AB  - Optimal prehospital care of near-drowning victims requires bystanders and
      emergency-response personnel who are knowledgeable in CPR and proper rescue
      techniques. Primary care physicians can play an important role when asked to
      teach CPR, first-responder, or emergency-care classes or to serve as medical
      director for a local ambulance group. Rapid response and appropriate ventilation
      and airway protection by prehospitalization providers can improve the condition
      of near-drowning victims on arrival in the emergency department and their chances
      for neurologically intact survival. With knowledge of the local risks of
      drowning, proper emergency treatment, appropriate referral, and conscientious
      efforts at prevention conducted in the office and the community, primary care
      physicians can have maximum impact on this summer-time killer.

PMID- 9633548
TI  - Acute sinusitis in adults. The Institute for Clinical Systems Integration.

PMID- 9633549
TI  - Valvular and coronary heart disease. When is it time for surgical referral?
AB  - Decisions about when to refer patients for cardiac surgery remain dynamic in the
      face of rapidly advancing technology. Coexisting health problems obviously play
      an important role, as do the natural history of the cardiovascular disorder, the
      indications for surgery, and the risks associated with the operative procedure.
      Nonetheless, many patients can be offered the possibility of improved
      cardiovascular function and survival through cardiac interventions.

PMID- 9633550
TI  - Evaluating facial paralysis. Expensive diagnostic tests are often unnecessary.
AB  - In most cases, the cause of facial paralysis can be determined on the basis of
      the clinical evaluation, and expensive diagnostic tests can be avoided. Because
      Bell's palsy is not always the cause, physicians need to be able to identify
      critical findings on history and physical examination that indicate an
      alternative diagnosis. Once identified, these findings can lead to a specific and
      directed evaluation.

PMID- 9633551
TI  - The case of the confusing cardiogram. Multifocal atrial tachycardia.

PMID- 9633552
TI  - Thrombotic thrombocytopenic purpura that is refractory to therapeutic plasma
      exchange in two patients with occult infection.
AB  - BACKGROUND: The etiology of thrombotic thrombocytopenic purpura (TTP) remains
      undetermined. TTP has been associated with a number of secondary causes including
      infections, drugs, menses, pregnancy, autoimmune diseases, and bone marrow
      transplantation. Regardless of the inciting factors, it is widely accepted that
      endothelial injury and platelet aggregation are integral components. The
      morbidity and mortality have been significantly reduced with the use of
      plasmapheresis. However, refractory forms of TTP remain a clinical management
      challenge. Refractory TTP has not previously been associated with occult
      bacterial infection. CASE REPORT: Two patients had classic TTP that was
      refractory to daily plasma exchange with fresh-frozen plasma. Multiple attempts
      over a period of months to wean these patients off plasma exchange resulted in
      exacerbations of disease activity, as indicated by increased schistocytosis,
      decreased hematocrit, increased serum lactate dehydrogenase, and decreased
      platelet counts. Both patients were empirically treated for infections during
      hospitalization, although microbial cultures failed to isolate an organism.
      Discontinuation of antimicrobial therapy on multiple occasions in one patient was
      associated with recurrence of disease. In the other patient, dental extraction
      with drainage of an occult periodontal abscess resulted in sustained remission of
      disease. CONCLUSION: Occult bacterial infection may play a role in triggering and
      sustaining TTP that is refractory to conventional treatment. A careful search for
      such an infection and appropriate antimicrobial therapy should be considered in
      the management of these patients.

PMID- 9633553
TI  - Effect of 24-hour storage at 25 degrees C on the in vitro storage characteristics
      of CPDA-1 packed red cells.
AB  - BACKGROUND: Packed red cells (RBCs) warmed above 10 degrees C are generally
      discarded. Few data exist on the degree of accelerated metabolism and increased
      hemolysis of packed RBCs allowed to warm. STUDY DESIGN AND METHODS: Twenty-four
      CPDA-1 packed RBC units were combined in 3-unit pools and subdivided into 2 test
      units and a control unit. One test unit from each pool was warmed to 25 degrees C
      for 24 hours on Day 6 and the other test unit was warmed on Day 20; control units
      were maintained at 1 to 6 degrees C. RBC and supernatant chemistries and RBC
      morphology were measured weekly (Days 0, 7, 14, 21, and 28) and on the day before
      warming (Days 6 and 20). RESULTS: Warming CPDA-1 packed RBCs accelerated the
      catabolism of glucose 10-fold and produced concentrations of glucose, lactate,
      and ATP after 25 days of storage that were equivalent to those in unwarmed units
      at 35 days. Supernatant sodium and potassium concentrations were corrected
      partially with warming. RBC morphology transiently normalized with warming and
      without increased hemolysis; no bacteria growth was detected. CONCLUSION: One day
      of 25 degrees C storage of CPDA-1 packed RBCs accelerates essential metabolite
      break-down equivalent to 10 days of storage at 1 to 6 degrees C. It does not
      appear to matter whether the packed RBCs are warmed on Day 6 or Day 20. This
      information may be useful in determining the acceptability of blood allowed to
      warm above 10 degrees C.

PMID- 9633554
TI  - Quality control of white cell-reduced red cells: white cell preservation and
      simplified counting.
AB  - BACKGROUND: White cell (WBC) degradation restricts the interval between the
      filtration process and the assay for residual WBCs. Maintaining WBC integrity
      would permit extended sample storage for batching and/or shipment to centralized
      laboratories. The usual quality control assay for WBC-reduced red cell units
      requires determining the number of WBCs in the entire counting area of a Nageotte
      hemocytometer, which consists of 40 rows. Reducing the counting area would
      simplify the quality control procedure. STUDY DESIGN AND METHODS: Adsol red cell
      units were prepared either on the day of collection (Day 0) or on Day 1 and WBC
      reduced by filtration on the same day. By using prefiltration and postfiltration
      red cells, samples containing WBC concentrations of 15, 10, and 3 WBCs per microL
      were prepared by serial dilution. Identical samples were treated with
      glutaraldehyde and stored at either 20 to 24 degrees C or 1 to 6 degrees C. All
      samples were assayed on the day of component preparation and on Days 7 and 14.
      The numbers of WBCs corresponding to 10- and 40-row areas of the Nageotte
      hemocytometer were determined. RESULTS: For the conditions and WBC concentration
      range studied, no significant changes in WBC concentrations were observed through
      Day 14 for glutaraldehyde-treated samples stored at either temperature, although
      there were substantial decreases in untreated samples. A 10-row measurement was
      determined to be sufficient for identifying WBC-reduced red cell units passing
      the present limit of 5 x 10(6) residual WBCs. CONCLUSION: Glutaraldehyde
      treatment can preserve WBCs in red cell samples at least up to Day 14, which
      provides increased efficiency in quality control for laboratories. Current red
      cell WBC-reduction filters produce components that, when assayed, contain fewer
      than 10 WBCs per full counting area. The simplified procedure would allow
      reduction of the counting area by 75 percent.

PMID- 9633555
TI  - RHD genotyping in weak D phenotypes by multiple polymerase chain reactions.
AB  - BACKGROUND: Weak D phenotypes involve a quantitative variation of D. The genomic
      basis in weak D has been disputed, however. STUDY DESIGN AND METHODS: Five
      sequence-specific polymerase chain reactions (SSP-PCRs) on exons 2, 5, and 7 of
      the RHD gene were evaluated in 248 white and 98 Japanese blood donors and
      compared with the results obtained by amplification of intron 4 and serology. All
      methods and SSP-PCR testing on the 3' non-coding region of the RHD gene were
      applied to the genotyping of 94 DNA samples derived from individuals expressing
      weak D phenotypes. RESULTS: Concordant results were obtained with all genotyping
      and phenotyping methods in testing 201 D-positive and 145 D-negative donors. Four
      of 94 weak D samples were typed as D-negative by amplification of intron 4 and
      SSP-PCR on exon 5. Phenotyping with monoclonal antibodies revealed a DVI category
      in one of these cases and DFR phenotype in three of these cases. One weak D
      sample, which reacted like normal D-positive cells with all applied monoclonal
      antibodies, was typed falsely negative by SSP-PCR on exon 5 because of a point
      mutation at nucleotide 667 (T-->G) that resulted in a Phe223Val amino acid
      substitution. In this individual, heterozygosity was found at two other amino
      acid positions (Glu233Gln and Val238Met) by restriction fragment length
      polymorphism analysis. CONCLUSION: Genetic diversity in weak D phenotypes is
      rare. Only 1 of 90 true weak D phenotypes (1.1%) had a genetic variation in
      testing on seven gene regions of the RHD gene.

PMID- 9633556
TI  - An Israeli family with six cisAB members: serologic and enzymatic studies.
AB  - BACKGROUND: The cisAB blood type is a rare phenomenon in which both the A and B
      blood types are inherited from a single parent. Several forms of this phenotype
      have been characterized that differ with respect to serologic reactions and the
      activities of the gene-encoded blood group A and B transferases. STUDY DESIGN AND
      METHODS: The cisAB blood type was suspected when a baby typed as blood group O
      was born to a mother whose blood group was AB. Family studies revealed four
      generations in whom the pattern of inheritance could be explained only by the
      inheritance of the cisAB genotype. Blood and saliva samples from the family were
      tested serologically and assayed for the relevant glycosyltransferases. Samples
      suitable for DNA analysis were not available. RESULTS: Six family members were
      shown serologically to be of the cisAB type. The A and B transferases in the sera
      of these individuals were 20 to 35 and 25 to 50 percent of those obtained for A
      and B individuals, respectively. The enzymic characteristics of the A and B
      transferases were determined. The A transferase in the sera of the cisAB persons
      did not bind to agarose beads. CONCLUSION: The family described carries the cisAB
      gene, which encodes production of A and B transferases that differ from those of
      "normal" A, AB, and B controls. This variant has properties that are distinctly
      different from those described in other reports.

PMID- 9633557
TI  - Increase in endogenous thrombopoietin in healthy donors after automated
      plateletpheresis.
AB  - BACKGROUND: Thrombopoietin (TPO) is a key cytokine involved in the regulation of
      megakaryocytopoiesis and platelet production. The aim of the present study was to
      test whether platelet donation is associated with changes in the serum TPO levels
      in healthy donors undergoing plateletpheresis. STUDY DESIGN AND METHODS: The
      study group consisted of 23 healthy donors undergoing single-donor
      plateletpheresis for the first time. Serum TPO levels and platelet counts were
      determined before platelet collection, at the end of apheresis, and for 4 days
      thereafter. Serum TPO levels were determined by a TPO-specific enzyme-linked
      immunosorbent assay. RESULTS: In relationship to platelet donation, serum TPO
      levels showed a temporary increase from baseline levels of 69.2 +/- 7.1 pg per mL
      to 117 +/- 6.8 pg per mL 2 days after plateletpheresis (p < 0.05). Further
      evaluation revealed a decline in serum TPO levels as platelet counts increased.
      Female donors showed a delayed normalization of circulating platelet numbers and
      serum TPO levels as compared to male donors. There was no significant correlation
      between serum TPO levels and the absolute platelet number during normalization of
      the donors' platelet counts after plateletpheresis. CONCLUSION: Single-donor
      plateletpheresis results in a temporary increase in serum TPO levels in healthy
      platelet donors, which may be part of a compensatory response-boosting
      megakaryocytopoiesis after platelet collection.

PMID- 9633558
TI  - Measurement of the levels of reticulated platelets after plateletpheresis to
      monitor activity of thrombopoiesis.
AB  - BACKGROUND: Little is known about the effects of long-term plateletpheresis on
      the donors' health. The aim of this study was to examine the effect of
      plateletpheresis on the time course of reticulated platelet counts as an estimate
      for thrombopoiesis. STUDY DESIGN AND METHODS: The effect of moderate platelet
      depletion on the thrombopoietic capacity was evaluated prospectively by the
      measurement of reticulated platelets before and after plateletpheresis and on the
      following 4 days. Donors undergoing plateletpheresis for the first time were
      compared to those donating platelets every other week for more than 18 months.
      RESULTS: The median levels of reticulated platelets were significantly lower in
      frequent donors than in new donors. In new donors, there was a transient increase
      in the median levels of reticulated platelets on Day 3 after apheresis, and
      baseline values were reached again on Day 4. On the contrary, in repeat donors,
      there was a sustained rise in the percentage of reticulated platelets from Days 1
      through 4. However, this increase in reticulated platelet counts was still less
      than that seen in new donors. There was no difference in the peripheral blood
      platelet counts in the two groups at any time point. CONCLUSION: These findings
      suggest that repeat platelet donation might lead to a relative exhaustion of
      thrombopoiesis, as evidenced by the low levels of reticulated platelets exhibited
      by repeat donors. The reticulated platelet count can be used to monitor the
      thrombopoietic capacity of long-term platelet donors.

PMID- 9633559
TI  - Release of mediators of systemic inflammatory response syndrome in the course of
      a severe delayed hemolytic transfusion reaction caused by anti-D.
AB  - BACKGROUND: In vitro studies suggest that mediators of systemic inflammatory
      response syndrome are generated in the course of hemolytic transfusion reactions.
      Evidence for the in vivo significance of these findings is given by the present
      clinical and laboratory analysis of a severe delayed hemolytic transfusion
      reaction (DHTR). CASE REPORT: A 67-year-old patient (blood group O, D-negative)
      with a negative pretransfusion antibody screen received a massive transfusion
      because of arterial bleeding (Day 1). The transfusion of group O, D-positive red
      cell concentrates was unavoidable because of limited supplies. At Day 10, the
      patient developed a DHTR with symptoms of septic-toxic syndrome and signs of
      hemolysis; he received an exchange transfusion. Serologic markers, as well as
      proinflammatory and anti-inflammatory mediators, were monitored at the onset of
      the DHTR and during the exchange transfusion. RESULTS: At Day 10, the direct
      antiglobulin test was positive; anti-D was present, most likely as the result of
      an anamnestic immune response. Interleukin (IL)-1 was not detectable; all other
      mediators monitored were elevated: IL-1 receptor antagonist, tumor necrosis
      factor, IL-6, IL-8, IL-10, neopterin, elastase, C3a-desArg, C-reactive protein,
      and fibrinogen. Most of the values declined during the exchange transfusion,
      which was followed by an improvement of the clinical presentation. CONCLUSIONS:
      Mediators of systemic inflammatory response syndrome were released in the course
      of a DHTR caused by anti-D. Severe clinical symptoms could be treated
      successfully by exchange transfusion.

PMID- 9633560
TI  - The effects of dilution on the outcome of pooled plasma testing with HIV type 1
      (HIV-1) RNA genome amplification as compared to the outcome of individual-unit
      testing with other HIV-1 markers.
AB  - BACKGROUND: Proposed testing of large plasma pools with genome amplification
      technology (GAT) for detection of transfusion-transmissible viruses may have
      unanticipated complications not associated with individual unit testing. One such
      potential complication, the effect of dilution resulting from pool formation, was
      the subject of the present study. STUDY DESIGN AND METHODS: Specimens from three
      plasma donor HIV type 1 (HIV-1) seroconversion panels were tested with a
      quantitative HIV-1 RNA GAT assay (lower detection limit, 400 copies). GAT results
      were compared to HIV-1 p24 antigen and anti-HIV-1/2 enzyme immunoassay results.
      Effects of dilution on the detection of GAT-positive panel specimens were
      assessed by terminal dilution with pooled volunteer-donor EDTA plasma samples.
      RESULTS: Low HIV-1 RNA copy numbers (755 and 890 copies/0.1-mL input) that were
      detectable in two individual plasma specimens before HIV-1 p24 antigen were
      subsequently undetectable by GAT upon dilution with an equal volume of
      nonreactive plasma from a single donor. HIV-1 RNA at higher copy numbers (15,500
      copies/0.1-mL input) in an HIV-1 p24 antigen-reactive and anti-HIV-1/2
      nonreactive specimen was undetectable when diluted to 1-in-50 (1-in-50). Terminal
      dilution of seven HIV-1 RNA-containing plasma panel specimens indicated a
      proportional loss of HIV-1 RNA detectability with increasing dilution.
      CONCLUSION: GAT for detection of HIV-1 RNA in individual specimens was more
      sensitive than other HIV markers. For pooled plasma testing, GAT-independent
      constraints, such as effects of dilution, may preclude the use of GAT detection
      as a replacement for individual unit testing with HIV serologic assays.

PMID- 9633561
TI  - Acute normovolemic hemodilution should replace the preoperative donation of
      autologous blood as a method of autologous-blood procurement.

PMID- 9633562
TI  - Acute normovolemic hemodilution is a legitimate alternative to allogeneic blood
      transfusion.

PMID- 9633563
TI  - Uses of antithrombin III concentrate in congenital and acquired deficiency
      states.

PMID- 9633564
TI  - New human leukocyte clusters of differentiation.

PMID- 9633565
TI  - Science, lawyers, and "the Europeans": testing requirements in transfusion
      medicine.

PMID- 9633566
TI  - Factors influencing the availability of umbilical cord blood for banking and
      transplantation.

PMID- 9633567
TI  - DNA typing of patients with potentially modified patterns in peripheral blood.

PMID- 9633568
TI  - Antibody screening for recent Yersinia enterocolitica infection in blood donors.

PMID- 9633569
TI  - Intranasal drug use among volunteer whole-blood donors: results of survey C.

PMID- 9633570
TI  - Platelet activation and interval between plateletpheresis.

PMID- 9633571
TI  - The pathophysiology of UPJ obstruction. Current concepts.
AB  - It took more than half of a century for urologists to recognize that
      hydronephrosis is not necessarily equivalent to obstruction. Keeping this
      important truism in mind, particularly when dealing with antenatal
      hydronephrosis, one must also remember that hydronephrosis is not a normal
      condition. It is conceivable that although the initial intrinsic stenosis or
      ureterovascular obstruction may not be clinically significant in terms of renal
      functional damage, as compensatory renal pelvic dilatation develops, secondary
      obstructive elements may be recruited to create an insertional anomaly and
      peripelvic fibrosis. The individual types of UPJ obstruction that are seen in
      diagnostic studies or on the operating table may represent isolated "snapshots"
      of evolving pathophysiologic processes. If this is true, patients with
      asymptomatic congenital hydronephrosis, although lacking obvious renal function
      loss, require long-term follow-up.

PMID- 9633572
TI  - Prenatal diagnosis. Therapeutic implications.
AB  - Prenatal diagnosis of structural anomalies provides the opportunity to influence
      the postnatal outcome. The greatest value of antenatal screening is, in fact, the
      awareness of the urogenital abnormalities, such as presumed UPJ obstruction, so
      that appropriate investigation and treatment can be offered immediately after
      birth and before permanent damage occurs owing to obstruction or infection.
      Crombleholme and coworkers reported that prenatal consultation impacted favorably
      on outcomes by preventing early termination of pregnancy owing to misconceptions
      about the existing condition. It also permitted delivery of complex cases in a
      tertiary care setting, thereby preventing a delay in postnatal management. A
      systematic approach to the infant in the prenatal and postnatal periods is
      important. The natural history of prenatally detected hydronephrosis continues to
      be defined, and there is no ideal test to predict the outcome of UPJ obstruction.
      Several investigators are evaluating various markers in urine that may help to
      identify fetuses who require early postnatal intervention. More complete
      understanding regarding the natural history of unilateral pediatric UPJ
      obstruction and its response to surgery will not be available until several
      randomized, prospective clinical studies are completed. The collaborative effort
      of obstetricians, neonatologists, geneticists, radiologists, and pediatric
      urologists should provide answers to many questions surrounding prenatally
      diagnosed UPJ obstruction.

PMID- 9633573
TI  - Neonatal management of unilateral hydronephrosis. Role for delayed intervention.
AB  - Hydronephrosis should be managed no differently in the newborn than in any other
      age group: UPJ obstruction should be surgically corrected as soon as the
      diagnosis is made. Unfortunately, the diagnosis of obstruction in the newborn
      with hydronephrosis is difficult and the traditional tests used in the older
      child or adult are not valid. Because newborn hydronephrosis is a relatively
      benign condition, surgical intervention should be delayed until the diagnosis of
      obstruction is proven. A protocol for evaluating the newborn with hydronephrosis
      is presented.

PMID- 9633574
TI  - Neonatal management. Role for early intervention.
AB  - Although performing pyeloplasty on an infant with a relatively healthy kidney
      prior to the onset of renal damage is not as well-accepted as "aggressive
      observation," the authors argue that early intervention is the more
      "conservative" or safe method of treatment for infants with ureteropelvic
      junction (UPJ) obstruction. Using experimental and clinical data, the authors
      demonstrate that prolonged partial UPJ obstruction in the developing kidney
      causes significant renal morbidity with time.

PMID- 9633575
TI  - Endourologic options for management of ureteropelvic junction obstruction in the
      pediatric patient.
AB  - Endourologic intervention is becoming a more widely accepted modality in the
      management of pediatric UPJ obstruction. The authors present five factors that
      are important in selecting patients that will lead to a successful treatment and
      outline techniques for antegrade and retrograde endopyelotomy and balloon
      dilation. This article also reviews the recent literature on endourologic
      interventions in the management of pediatric UPJ obstruction. The authors
      conclude that pediatric endopyelotomy has an 86% success rate and should be
      offered as treatment for select pediatric patients with UPJ obstruction.

PMID- 9633576
TI  - Ureteropelvic junction obstruction in children. Unique considerations for open
      operative intervention.
AB  - The treatment of UPJ obstruction in children should be approached in a fashion
      that recognizes the differences between children and adults. Radiographic
      definition of the urinary tract is different in children than in adults because
      of the size of the child and technical difficulties with instrumentation.
      Retrograde pyelography, in general, is not necessary in children, although this
      decision must be individualized. The surgical incision should be chosen based on
      the size of the child and the unique considerations of individual renal anatomy
      and pathology, as well as the surgeon's experience. In children, tubeless surgery
      may be performed with excellent results, however, diversion with nephrostomies
      and stents may be necessary in selected cases. With attention to technical
      details and the unique considerations in children, the results of repair of the
      UPJ should be excellent and reproducible.

PMID- 9633577
TI  - Ureteropelvic junction obstruction in anomalous kidneys.
AB  - UPJ obstructions occurring in anomalous kidneys require special consideration.
      Many anomalous kidneys are dysmorphic with extrarenal pelves, making the
      distinction between obstructed and nonobstructed hydronephrosis crucial. The
      radiographic evaluation must be thorough because there are often other associated
      anomalies of the ipsilateral or contralateral kidney. Operative intervention must
      be tailored to the specifics of the case. Although most UPJ obstructions in
      anomalous kidneys can be reconstructed successfully with dismembered pyeloplasty
      or treated with newer minimally invasive techniques, issues regarding access,
      operative detail, and adjunct procedures make these cases challenging for the
      urologic surgeon.

PMID- 9633578
TI  - Provocative imaging. Diuretic renography.
AB  - Diuretic renography remains the noninvasive functional study of choice in
      patients with hydronephrosis resulting from apparent UPJ obstruction. Meticulous
      attention to proper patient preparation, radiopharmaceutical selection,
      furosemide dosage and administration, and image interpretation and an awareness
      of potential pitfalls are essential for accurate diagnosis. For most patients,
      the F + 20 protocol is sufficient, however; the F-15 protocol allows
      clarification in cases of equivocal baseline F + 20 studies. Invasive antegrade
      techniques such as the Whitaker pressure/perfusion test are best reserved for
      patients in whom the diagnosis remains equivocal after diuretic renography, or in
      patients with massive hydronephrosis or renal insufficiency. New standardized
      protocol guidelines should help to ensure studies that are reproducible in
      different nuclear medicine laboratories.

PMID- 9633579
TI  - Vascular anatomy at the ureteropelvic junction.
AB  - In 65% of the cases regarding the ventral surface of the UPJ, there was a
      prominent artery, vein, or both in close relation to the ventral surface of the
      UPJ. In only 6.8% there was an inferior polar artery crossing anteriorly to the
      UPJ. Therefore, many of the vessels visualized close to the UPJ and described as
      anomalous and etiologic in obstruction are normal segmental arteries that do not
      cause UPJ obstruction. In 26.7% of cases regarding the dorsal surface of the UPJ,
      there was a vessel crossing at or lower than 1.5 cm above the posterior surface
      of the UPJ. On the basis of our anatomic findings, we advise that in
      endopyelotomy, the incision along the stenotic UPJ be created only at its lateral
      aspect.

PMID- 9633580
TI  - Helical CT and CT angiography for the identification of crossing vessels at the
      ureteropelvic junction.
AB  - In comparison with pyeloplasty, endourologic procedures for the treatment of
      ureteropelvic junction obstruction offer good success rates with less morbidity
      and a shorter hospitalization; however, studies have found lower success rates
      and increased complications in patients with crossing vessels. Conventional
      diagnostic angiography and intravenous urography have both been used to identify
      crossing vessels at the UPJ; but, a reliable, less invasive, less costly, and
      simpler preoperative procedure to identify crossing vessels is needed. Helical CT
      with CT angiography is a promising noninvasive technique for the identification
      of crossing vessels at the ureteropelvic junction, which can be used for surgical
      planning of endourologic treatment of UPJ obstruction.

PMID- 9633581
TI  - Endoureteral sonography to define the anatomy of the obstructed ureteropelvic
      junction.
AB  - Endoluminal ultrasound of the obstructed ureteropelvic junction (UPJ) provides
      accurate anatomic information not available through other studies. Endoluminal
      ultrasonography in the evaluation of the obstructed UPJ can be extremely valuable
      and its use can be expected to expand with increasing experience with the
      techniques. The anatomy demonstrated through the fine resolution of this
      technique may ultimately provide the key to the selection of optimal therapy for
      the obstructed UPJ.

PMID- 9633582
TI  - Endopyelotomy. Prognostic factors and patient selection.
AB  - Although clearly a valid alternative to dismembered pyeloplasty for ureteropelvic
      junction obstruction in adults, endo(uretero)pyelotomy has not been universally
      accepted in the general urologic community because of the 10% to 30% inferior
      success rate and the concern regarding hemorrhagic complications. Identification
      of prognostic factors for success and complications are therefore of primary
      importance. The length of stricture, the grade of hydronephrosis, and the level
      of renal function are well recognized prognostic factors. Crossing vessels also
      play a role, and in association with the grade of hydronephrosis, they seem to be
      a major prognosticator of outcome. With attention to such prognostic factors, and
      appropriate patient selection, results can now approach the gold standard of
      dismembered pyeloplasty.

PMID- 9633583
TI  - Crossing vessels. Endourologic implications.
AB  - The controversy regarding the functional significance of vessels crossing at the
      ureteropelvic junction is not a new one, though this debate has been resurrected
      in recent years because of application of endourologic techniques to manage
      ureteropelvic junction (UPJ) obstruction. The principle limitation of endoscopic
      treatment of UPJ obstruction is the inferior success rate compared to open
      dismembered pyeloplasty. The influence crossing vessels may have in affecting
      both the success rates and complications of endoscopic treatment of UPJ
      obstruction has yet to be resolved. Crossing vessels may be important for two
      reasons: (1) they are a potential source of hemorrhage following endoscopic
      incision, and (2) they may play an etiologic role in UPJ obstruction and
      therefore may be a reason for failure of endoscopic techniques. This article
      reviews some of the historical aspects of crossing vessels and explores recent
      studies that are starting to shed some light on this controversial topic.

PMID- 9633584
TI  - Retrograde balloon cautery incision of ureteropelvic junction obstruction.
AB  - Retrograde balloon endopyelotomy has produced durable success rates of
      approximately 80% for all patients with UPJ obstruction. Patients with poor renal
      function, high-grade hydronephrosis, or stricture lengths of more than 2 cm fair
      worse, and these factors should be considered prior to balloon endopyelotomy. The
      debate concerning the functional significance of crossing vessels continues.
      However they are probably more important in terms of the risk of postoperative
      bleeding than in regards to overall success rates. With the use of endoluminal
      ultrasound, angiography, or spiral CT, patients with significant size crossing
      vessels can be identified preoperatively. The retrograde approach to UPJ
      obstruction using a cutting balloon is a quick and relatively inexpensive
      (shorter operative time and hospital stay, and no percutaneous nephrostomy)
      method for accomplishing an endopyelotomy incision. With the development of the 5
      F balloon catheter and the use of a 7-F post-endopyelotomy stent, the need to
      stent the ureter for 7 days prior to the procedure is overcome. In this regard,
      the entire retrograde endopyelotomy may be performed in a one-step outpatient
      procedure.

PMID- 9633585
TI  - Endopyelotomy. Retrograde ureteroscopic approach.
AB  - Ureteroscopy is a natural extension of a urologist's practice. This article
      describes technical details and results using the ureteroscopic approach to treat
      ureteropelvic junction obstruction. With a variety of treatment options
      available, this approach compared favorably.

PMID- 9633586
TI  - Antegrade endopyelotomy.
AB  - Antegrade endopyelotomy has become the procedure of choice for patients with UPJ
      obstruction. Overall success rates of 85% can be expected when the procedure is
      used in a broad spectrum of patients. Contraindications include an uncorrected
      bleeding diathesis, untreated infection, and any anatomic abnormality precluding
      safe percutaneous access.

PMID- 9633587
TI  - Ureteropelvic junction obstruction and renal calculi. Pathophysiology and
      implications for management.
AB  - Ureteropelvic junction (UPJ) obstruction is a well-studied phenomenon in terms of
      its etiology, implications for renal function, and clinical management. The
      presence of concomitant ipsilateral calculus disease, however, introduces a
      confounding variable into the understanding of this entity. This article
      discusses the relationship between renal calculi and UPJ obstruction as it
      pertains to their pathophysiology and clinical management as combined entities.

PMID- 9633588
TI  - Laparoscopic pyeloplasty. Indications, technique, and long-term outcome.
AB  - Laparoscopic pyeloplasty is one of several minimally invasive treatment options
      for UPJ obstruction. In fact, several endoscopically and fluoroscopically
      controlled methods of incising the obstructed UPJ are now available that are
      significantly less invasive and less morbid in comparison with open pyeloplasty.
      However, the long-term success rates of these incisional techniques are less than
      the rates reported for open pyeloplasty. Several causes of obstruction may be
      present in the primarily obstructed UPJ, including kinking or compression related
      to crossing vessels or intrinsic narrowing at the UPJ. One potential reason for
      the inferior success rates of incisional methods in comparison with open
      pyeloplasty is that the former techniques address the intrinsically narrowed UPJ
      but may not address extrinsic problems such as kinking of the ureter associated
      with fibrotic bands or compression from crossing vessels. Laparoscopic
      pyeloplasty addresses all potential causes of obstruction. Any fibrotic bands
      kinking the ureter are divided, and the ureter is spatulated through the level of
      the UPJ prior to completion of the anastomosis. If a crossing vessel is
      encountered, a dismembered pyeloplasty is performed, the ureter and renal pelvis
      are transposed to the opposite side of the vessels, and the anastomosis is
      completed. An additional disadvantage of incisional techniques is the significant
      risk of hemorrhage following incision of the UPJ, with as many as 3% to 11% of
      patients requiring blood transfusion. Hemorrhage may occur owing to an errant
      anterior incision, the presence of a crossing vessel, incision into the renal
      parenchyma adjacent to the UPJ, or as the result of bleeding from the
      percutaneous access site. In contrast, mean estimated blood loss in the authors'
      series of 57 laparoscopic pyeloplasties was 139 mL, and none of the patients
      required blood transfusion. Although it is more morbid in comparison with
      retrograde or fluoroscopically controlled endopyelotomy, laparoscopic pyeloplasty
      seems at least comparable to antegrade percutaneous endopyelotomy in terms of the
      length of hospitalization and patient convalescence. Laparoscopic pyeloplasty,
      however, offers a higher success rate than with incisional techniques, not only
      from a radiographic standpoint but from a subjective standpoint as determined by
      the results of the analogue pain and activity questionnaire. The major
      disadvantage of laparoscopic pyeloplasty is the need for proficiency in
      laparoscopic techniques and for a longer operative time. As a result, the
      literature on laparoscopic pyeloplasty consists primarily of small series.
      Janetschek and co-workers reported on a series of 17 patients who underwent
      laparoscopic pyeloplasty, including 14 via a transperitoneal approach and 3 via a
      retroperitoneal approach. Procedures performed included ureterolysis alone,
      dismembered pyeloplasty, and nondismembered (Fenger) pyeloplasty. "Fenger-plasty"
      is similar to Y-V pyeloplasty and is performed by incising the UPJ longitudinally
      and closing the incision transversely in a Heineke-Mikulicz fashion. Janetschek
      and colleagues reported a 100% success in the eight patients who underwent
      dismembered pyeloplasty but believed that this technique was too cumbersome and
      should be reserved for patients with long stenoses, dorsally crossing vessels, or
      large renal pelvis. Because two of the four patients undergoing ureterolysis
      alone failed treatment, Janetschek and colleagues have abandoned this technique.
      They now prefer the Fenger-plasty technique, even in the setting of ventrally
      crossing vessels, because the technique can be performed quickly with one to
      three sutures, and the anastomosis can be sealed with fibrin glue and a flap of
      Gerota's fascia. Their experience with this technique, however, remains
      relatively limited. Technologic advances such as the Endostitch device have
      facilitated reconstructive laparoscopic procedures such as pyeloplasty. (ABSTRACT
      TRUNCATED)

PMID- 9633589
TI  - Ureteropelvic junction obstruction. Open operative intervention.
AB  - The indications to intervene for ureteropelvic junction (UPJ) obstruction have
      not changed despite the introduction of newer, less invasive techniques for
      definitive management. In contemporary practice, open operative intervention is
      still appropriate for those patients in whom alternative management has failed or
      is contraindicated, or for those in whom an unobstructed UPJ needs to be assured
      with the highest certainty--both immediately and with long-term follow-up.
      Although several techniques have been described for open operative reconstruction
      of an obstructed UPJ, a dismembered pyeloplasty has proven to be the most
      versatile, and should be a part of every urologist's treatment armamentarium.
      Alternative primary and salvage techniques for open operative reconstruction of
      the UPJ are also described in this article.

PMID- 9633590
TI  - Retroperitoneal laparoscopic nephrectomy.
AB  - When removal of a kidney is indicated for symptomatic end-stage renal disease of
      benign etiology, laparoscopic nephrectomy by the retroperitoneal approach is
      increasingly being employed as the technique of choice at many centers. Emerging
      data indicate that, in select patients with T1-T3aN0M0 renal tumors < 8 cm,
      retroperitoneal laparoscopic radical nephrectomy may be a viable treatment
      option.

PMID- 9633591
TI  - Unfolding/folding studies on cobrotoxin from Taiwan cobra venom: pH and GSH/GSSG
      govern disulfide isomerization at the C-terminus.
AB  - Refolding of cobrotoxin was assessed by the exposure degree of its single Trp
      determined by an acrylamide quenching study. The change in the accessibility of
      Trp for acrylamide quantitatively reflected the formation of folded cobrotoxin,
      and the data were confirmed by HPLC and gel electrophoresis analyses. However,
      the site-specific information provided by quenching Trp fluorescence revealed
      that the ordered structure in the neighborhood of Trp was attained prior to the
      complete formation of the tertiary structure of cobrotoxin. HPLC analyses showed
      that, in addition to refolded cobrotoxin, two novel species (cobrotoxin II and
      cobrotoxin III) with isomerization of disulfide bonds at the C-terminus of the
      toxin molecule were produced along the folding reaction. The disulfide pairings
      in cobrotoxin II and cobrotoxin III were Cys43-Cys55 and Cys54-Cys60 and Cys43
      Cys60 and Cys54-Cys55, respectively. Among the three possible two-disulfide
      species at the C-terminus, the disulfide linkages Cys43-Cys60 and Cys54-Cys55 of
      cobrotoxin III caused a marked decrease in lethality and resulted in a
      conformation which was notably different from that observed with the native toxin
      molecule as evidenced by CD spectra. The refolding reaction was accelerated by
      the addition of GSH/GSSG, and the resulting products were mostly folded
      cobrotoxin. However, if GSH/GSSG was not added into the initial folding
      materials, the yields of cobrotoxin II and cobrotoxin III greatly increased. The
      conversion of cobrotoxin to its isomers was to be irreversible and pH-dependent:
      the higher the pH, the faster the rate of conversion. However, this conversion
      could be partly inhibited by GSH/GSSG. Cobrotoxin II and cobrotoxin III were
      purified from Taiwan cobra venom as well, and their yields in comparison to that
      of cobrotoxin in venom were similar to that noted with the folded products in the
      presence of GSH/GSSG. Moreover, the rate of disulfide isomerization was expected
      to be slow in venom fluid in which the pH was approximately pH 6.2. Thus, the
      finding that cobrotoxin represents the predominant neurotoxin species in Taiwan
      cobra venom is probably associated with the synergistic effects of GSH/GSSG and
      pH.

PMID- 9633592
TI  - Endotoxin pretreatment in vivo increases the mitochondrial respiratory capacity
      in rat hepatocytes.
AB  - Administration of sublethal doses of endotoxin produces tolerance to subsequent
      oxidative stress in diverse animal models. Although endotoxin induces antioxidant
      enzymes, particularly manganous superoxide dismutase (Mn-SOD), the phenomenon of
      tolerance remains incompletely understood. Previously I determined that endotoxin
      treatment in rats increased lung mitochondrial respiration-dependent (i.e.,
      independent of Mn-SOD) scavenging of superoxide anion. Because nonenzymatic
      scavenging of superoxide anion correlates with the mitochondrial membrane energy
      gradient, I hypothesized that endotoxin increases the mitochondrial transmembrane
      potential. Endotoxin treatment (500 micrograms/kg intraperitoneally 48 h earlier)
      increased the hepatocyte mitochondrial transmembrane potential as determined by
      two separate methods: the intramitochondrial sequestration of
      triphenylmethylphosphonium (electrical potential or delta psi) and the
      fluorescence intensity of the hepatocyte mitochondria when stained with rhodamine
      123 and examined by confocal microscopy. These findings suggest that endotoxin
      treatment increased the total mitochondrial membrane potential per hepatocyte. In
      parallel, endotoxin treatment increased the fluorescence intensity of hepatocyte
      mitochondria after staining with 10-N-nonyl-acridine orange, a dye that binds to
      the mitochondrial inner membrane independently of the transmembrane potential.
      This suggests that an increase in mitochondrial inner membrane mass is
      responsible for the net increase in inner membrane potential per cell following
      endotoxin pretreatment. These findings complement previous studies in which
      endotoxin treatment increased the mitochondrial-specific antioxidant Mn-SOD and
      support the more recent finding that endotoxin treatment also increased
      nonenzymatic scavenging of superoxide by lung mitochondria. Taken, together,
      these observations suggest that mitochondrial biogenesis, and the subsequent
      increase in both enzymatic and nonenzymatic scavenging of superoxide anion, is a
      central feature of endotoxin-mediated tolerance to oxidative stress.

PMID- 9633593
TI  - Oxidation of dilinoleoyl phosphatidylcholine by lipoxygenase 1 from soybeans.
AB  - Soybean lipoxygenase-1 is able to oxidize dilinoleoyl phosphatidylcholine at pH
      7.5 and 10. The reaction could be followed spectrophotometrically from the
      increase of the absorbance at 234 nm. An intermediate product and a final product
      were detected. In the intermediate product only one of the linoleoyl chains
      (either sn1 or sn2) was oxidized. In the final product, both linoleic acid units
      were converted into hydroperoxides. Apparently, oxidation of one of the linoleoyl
      chains leads to a disruption of the structure of the mixed bilayer disk, making
      the remaining fatty acid unit more accessible to the action of the enzyme. The
      specificity of lipoxygenase-1 when acting on phospholipids is not affected by pH.
      The exclusive production of 13-hydroperoxyoctadecadienoic acid derivatives of
      dilinoleoyl phosphatidylcholine at pH 7.5 and 10 may result from the blockage of
      the carboxylic end of the fatty acid.

PMID- 9633594
TI  - The fibronectin-like domain is required for the type V and XI collagenolytic
      activity of gelatinase B.
AB  - Gelatinase B (matrix metalloproteinase-9) is able to degrade several
      extracellular matrix proteins, including gelatin, elastin, and collagen types IV,
      V, XI, and XIV. This enzyme contains a "fibronectin-like" domain which is
      composed of three tandem copies of a fibronectin type 2 homology unit inserted
      into its catalytic domain. We have studied the involvement of this domain in the
      substrate specificity of gelatinase B by expressing a mutant of the enzyme, in
      Escherichia coli, in which this domain has been deleted. This mutant enzyme
      retained its ability to cleave the peptide substrate Mca-PLGL(Dpa)AR-NH2,
      possessing K(m) and kcat values similar to those of the wild-type enzyme. In
      addition, the NH2-terminal, 14-kDa, inhibitory domain of recombinant tissue
      inhibitor of metalloproteinase-2 was able to inhibit the mutant and the wild-type
      enzymes with the same potency. The mutant's gelatinolytic activity was also
      retained but reduced in comparison to that of the wild-type enzyme. However,
      contrary to the wild-type enzyme, the mutant was not able to digest or bind
      fibrillar collagen types V and XI. These data indicate that the fibronectin-like
      domain of gelatinase B is an important determinant of the enzyme's fibrillar
      collagen substrate specificity. It allows the enzyme to bind to and cleave
      collagen types V and XI, events which are thought to be involved in several
      normal physiological and pathological processes such as metastasis and arthritis.

PMID- 9633595
TI  - Polysaccharide lyase: molecular cloning of gellan lyase gene and formation of the
      lyase from a huge precursor protein in Bacillus sp. GL1.
AB  - A bacterium, Bacillus sp. GL1, produced constitutively the extracellular
      polysaccharide-degrading enzyme (gellan lyase) with a molecular mass of 140 kDa.
      A genomic DNA library of the bacterium was constructed in Escherichia coli using
      the cosmid vector, Charomid 9-36. The gene encoding the lyase was cloned by
      screening for a gellan-degrading phenotype in E. coli cells and the nucleotide
      sequence of the gene was determined. The gene contained an open reading frame
      consisting of 7425 base pairs coding a polypeptide with a molecular mass of 263
      kDa. The polypeptide contained the same amino acid sequence as N-terminal amino
      acid sequence of the enzyme and exhibited no homology with any previously
      published protein sequences. E. coli cells transformed with the gene exhibited
      gellan lyase activity and produced a protein with a molecular mass of about 260
      kDa intracellularly. The protein was purified and shown to have the closely
      similar enzymatic properties to those of the native enzyme from Bacillus sp. GL1
      with respect to optimal pH and temperature for activity, substrate specificity,
      and the mode of enzyme action. These results suggest that, in Bacillus sp. GL1,
      gellan lyase is first produced as a huge precursor protein (263 kDa) and then the
      protein is posttranslationally processed into extracellular mature form (140 kDa)
      through excising C-terminal peptide of about 120 kDa.

PMID- 9633596
TI  - Purification and characterization of monomeric lysine decarboxylase from soybean
      (Glycine max) axes.
AB  - Lysine decarboxylase (EC 4.1.1.18) was purified 364-fold from 2-day-old soybean
      (Glycine max) axes. The enzyme was a monomeric protein having a molecular mass of
      95,000 Da and an isoelectric point of 4.0. The K(m) for L-lysine was 1.17 mM. The
      optimal temperature and pH of the enzyme were 37 degrees C and 7.5, respectively.
      Storage of the enzyme at temperature ranging from 0 to 4 degrees C caused a 50%
      loss of the activity in 24 h. The enzyme was competitively inhibited by Cl- with
      a Ki value of 1.46 mM. However, the activity of the purified enzyme was not
      inhibited by F-, Br-, I-, H2PO4-, HPO4(2-), or SO4(2-). Cadaverine at 1 mM
      inhibited the enzyme activity by 35%.

PMID- 9633597
TI  - Purification, properties, and multiple forms of a manganese-activated inorganic
      pyrophosphatase from Bacillus subtilis.
AB  - The hydrolysis of magnesium pyrophosphate by inorganic pyrophosphatase from
      Bacillus subtilis required its specific, time-dependent, and prior activation by
      Mn2+ ions. This was reversed when Mn2+ ions were removed with EDTA. Free Mn2+
      ions were not required for catalysis. Pyrophosphatase purified to near
      homogeneity gave a single main band of apparent M(r) 36,000 by SDS-PAGE, but of
      M(r) 34,000 by matrix-assisted laser desorption ionization-mass spectrometry. The
      native enzyme equilibrated at pH 7 between three distinct molecular forms.
      Exposure to Mn2+ generated a catalytically active trimer of specific activity
      about 5000 mumol pyrophosphate hydrolyzed/min/mg protein. Exposure to EDTA
      generated two catalytically inactive forms, a dimer at low ionic strength and a
      separate form, of uncharacterized multimeric nature, at molar concentrations of
      Na2SO4 or Li2SO4. The latter form was an intermediate in the dimer-trimer
      transition caused by addition or removal of manganese ions. Mn2+ reacted with
      this "intermediate" form, apparently by reversible association with two
      noninteracting binding sites of Kd approximately 0.005 and 0.35 microM,
      respectively. The properties of this enzyme may account in part for the unusual
      manganese requirements of B. subtilis and related species.

PMID- 9633598
TI  - Aldehyde dehydrogenase (CoA-acetylating) and the mechanism of ethanol formation
      in the amitochondriate protist, Giardia lamblia.
AB  - The so far unelucidated pathway of formation of ethanol, one of the major end
      products of the fermentative metabolism of the amitochondriate protist, Giardia
      lamblia, was examined. Two NAD-dependent enzymatic activities, an acetaldehyde
      dehydrogenase (CoA-acetylating) (EC 1.2.1.10) and an alcohol dehydrogenase (EC
      1.1.1.1) were detected. These are assumed to catalyze the formation of ethanol
      from acetyl-CoA via acetaldehyde. The first activity, present on a 95-kDa
      protein, was purified. It catalyzed the reversible interconversion of acetyl-CoA
      to acetaldehyde and CoA-SH with NAD but not NADP as cofactor. In the direction of
      aldehyde formation acetyl-CoA was the preferred substrate. Propionyl-CoA and
      isobutyryl-CoA were reduced with lower efficiency while succinyl-CoA and benzoyl
      CoA were not. In the direction of acyl-CoA formation, acetaldehyde was the
      preferred substrate. Propionaldehyde and isobutyraldehyde were utilized at a
      lower efficiency while formaldehyde, benzaldehyde, and acetone were not. The
      second activity, a primary alcohol dehydrogenase, was also NAD-specific and used
      preferentially ethanol as substrate. Sequencing data of peptides from the
      purified protein and Northern and Southern analysis indicated that the same
      polypeptide, which belongs to the bifunctional aldehyde/alcohol dehydrogenase
      enzyme family, carried both activities. These activities define the pathway to
      ethanol in G. lamblia as a two step-processes: (i) acetyl-CoA + NADH<-
      >acetaldehyde + CoA-SH + NAD+ and (ii) acetaldehyde + NADH<-->ethanol + NAD+. In
      contrast to most eukaryotes in which ethanol formation proceeds from pyruvate via
      acetaldehyde, the G. lamblia pathway departs from acetyl-CoA, a more distal
      product of extended glycolysis.

PMID- 9633599
TI  - Reactions of pyridine coenzyme dimers and monomers with viologens.
AB  - DCMV++ (1,1'-dimethyl-2,2'-dicyano-4,4'-bipyridinium, bis-methylsulfate) promotes
      the aerobic oxidation of the NAD(P) dimers (NADP)2 and (NAD)2 with the formation
      of 2 mol of NADP+ or NAD+ per mole of dimers. The reaction appears to follow a
      pseudo-first-order kinetics with respect to the dimer concentration. One mole of
      oxygen was consumed in the reaction per mole of NAD(P) dimer oxidized and
      hydrogen peroxide was produced. The monomers NADPH and NADH under the same
      reaction conditions were not oxidized by DCMV++. In anaerobiosis NAD(P) dimers
      but not NAD(P)H rapidly reduced DCMV++ to its radical cation DCMV++, which was
      rapidly back-oxidized by air to its parent dication. Paraquat (MV++) was also
      able to catalyze the aerobic oxidation of NAD(P) dimers and, at a much lower
      extent, NADPH and NADH, but only under light irradiation. In anaerobiosis and
      upon light irradiation all the above nucleotides were able to convert paraquat to
      its radical cation MV++, reoxidized to MV++ by air admission. This study shows
      the different ability of NAD(P) dimers and NAD(P)H to undergo one-electron and
      two-electron oxidation reactions, with different viologens.

PMID- 9633600
TI  - pH dependence of the reaction rate of p-bromophenacyl bromide and of the binding
      constants of Ca2+ and an amide-type substrate analog to bovine pancreatic
      phospholipase A2.
AB  - pH dependence of the chemical reaction rates of p-bromophenacyl bromide (BPB) and
      of the binding constants of Ca2+ to bovine pancreatic active- and pro
      phospholipases A2 (PLA2s) was studied at 25 degrees C and ionic strength 0.2. The
      pH dependence curves of the reaction rates of BPB with both enzymes were
      biphasic. The amino acid residues participating in the two transitions were
      ascribed to His 48 and the N-terminal alpha-amino group for the active enzyme and
      to His 48 and Arg -1 for the proenzyme. The pH dependence curve of Ca2+ binding
      to the active enzyme was interpreted in terms of participation of Asp 49, His 48,
      and the alpha-amino group. On the other hand, the curve for the proenzyme was
      interpreted in terms of participation of Asp 49, His 48, and Arg -1. The Ca2+ and
      pH dependence of the binding constant of a potent competitive inhibitor,
      monodispersed (R)-2-dodecanoylamino-1-hexanol-phosphocholine (amide-PC), to
      bovine pancreatic active-PLA2 was also studied. The binding of amide-PC was
      markedly facilitated by Ca2+ binding to the enzyme, whereas that of a genuine
      substrate, monodispersed 1,2-dihexanoyl-sn-glycero-3-phosphorylcholine (diC6PC),
      was independent of Ca2+ binding. The pH dependence curve of the binding constant
      of the amide-PC showed one transition, and this was interpreted in terms of
      participation of His 48, whereas the binding of the diC6PC was independent of the
      ionization state of His 48. The difference in the Ca2+ dependence for the
      bindings of the diC6PC and amide-PC was considered to arise from the fact that
      the amide group of amide-PC can form a hydrogen bond with His 48, whereas the
      genuine substrate cannot form such a hydrogen bond.

PMID- 9633601
TI  - Chromatographic assay and peptide substrate characterization of partially
      purified farnesyl- and geranylgeranyltransferases from rat brain cytosol.
AB  - A simple method for partially purifying both farnesyltransferase and
      geranylgeranyltransferase from rat brain cytosol is presented. Each of the final
      protein preparations contains one single transferase activity. A common method of
      measurement of both activities is described. The assay, which follows substrate
      prenylation, is also convenient for the measurement of the concomitant decrease
      in cosubstrates during the two transfer reactions. The quantitative HPLC
      detection of the prenylated substrates and of the cosubstrate consumption is used
      here to follow the purification processes. The same method is also used for
      substrate-specificity studies of the two enzymes performed on 18 synthetic
      hexapeptides derived from the C-terminus of proteins known to be prenylated in
      vivo. These studies partially confirm the reported differences in the substrate
      specificities of the two prenyltransferases. However, the observed recognition of
      overlapping sequences by the two enzymes might have important consequences for
      the inhibition of either of the enzymes in vivo and for the design of specific
      inhibitors.

PMID- 9633602
TI  - A conserved tryptophan at the ferredoxin-binding site of ferredoxin:nitrite
      oxidoreductase.
AB  - Treatment of spinach leaf ferredoxin-dependent nitrite reductase with N
      bromosuccinimide (NBS), under conditions where slightly less than 1 mol of
      tryptophan is modified per mole of nitrite reductase, inhibits the catalytic
      activity of the enzyme by ca. 80% without any effect on substrate binding or
      other enzyme properties. Complex formation between nitrite reductase and
      ferredoxin completely protects the enzyme against this inhibition. Transient
      kinetic measurements show that the second-order rate constant for reduction of
      NBS-modified nitrite reductase by reduced ferredoxin is approximately four-fold
      larger than that observed for the native, unmodified enzyme. Also, reduction of
      NBS-modified nitrite reductase by the 5-deazariboflavin radical shows a different
      kinetic pattern than that observed with the native enzyme, suggesting that
      tryptophan modification increases access of the radical to the low-potential [4Fe
      4S] cluster of the enzyme, decreases the accessibility to the siroheme group of
      the enzyme, or both. The tryptophan that is modified has been identified as the
      absolutely conserved W92. A methionine, M73, that is also modified by NBS, has
      been identified. The ferredoxin-binding site on spinach nitrite reductase thus
      appears to include W92 and perhaps M73, in addition to the previously identified
      R375, R556, and K436.

PMID- 9633603
TI  - An unassembled subunit of NAD(+)-dependent isocitrate dehydrogenase is insoluble
      and covalently modified.
AB  - The NAD(+)-dependent isocitrate dehydrogenase of Saccharomyces cerevisiae is an
      octamer composed of four Idh1p subunits and four Idh2p subunits. Isocitrate
      dehydrogenase functions in the tricarboxylic acid cycle and has also been
      reported to bind to the 5' nontranslated region of mitochondrially encoded mRNAs.
      Mutants defective in either or both of these subunits are unable to grow on the
      nonfermentable carbon source, acetate, but will utilize glycerol or ethanol.
      Mutant strains lacking Idh2p maintain normal if not elevated levels of
      mitochondrial Idh1p. In addition to the mature unassembled Idh1p subunit, a
      complex of bands in the 85- to 170-kDa range (Idh1p-Cpx) is observed using NAD
      IDH antiserum. Both Idh1p and Idh1p-Cpx are insoluble within the mitochondrion
      and are associated with the mitochondrial inner membrane. A histidine-tagged form
      of Idh1p was expressed in yeast strains. Chemical amounts of the Idh1p-Cpx could
      be purified from strains lacking Idh2p but not from strains containing normal
      levels of Idh2p. The data indicate that Idh1p-Cpx is an aggregated and cross
      linked form of Idh1p that may be oxidized within the mitochondrion as a
      consequence of its aborted assembly.

PMID- 9633604
TI  - Di- and oligosaccharide substrate specificities and subsite binding energies of
      pig intestinal glucoamylase-maltase.
AB  - The substrate specificity of pig intestinal glucoamylase-maltase was
      investigated. The alpha-1, beta-2-glycosidic bond of the disaccharide sucrose was
      not hydrolyzed. Various substrates with alpha-1,4-glycosidic bonds (maltose,
      maltooligosaccharides) were hydrolyzed with high maximal reaction velocities.
      Reduction lowered the rate of hydrolysis drastically: k'0 decreases from 75 s-1
      for maltose to 3 s-1 for maltitol while the K(m) value increases from 4.2 to 50
      mM. Leucrose with alpha-1,5-glycosidic bond was hydrolyzed with a k'0 value of 8
      s-1 and a K(m) value of 74 mM. Disaccharides with alpha-1,6-glycosidic bonds were
      hydrolyzed with extremely low rates: for isomaltose and isomaltulose k'0 values
      of 5 and 3 s-1, respectively, and K(m) values of 90 and 42 mM, respectively, were
      observed. Again reduction lowers the k'0 values: The corresponding disaccharide
      alcohols alpha-D-glucopyranosyl-1,6-sorbitol and alpha-D-glucopyranosyl-1,6
      mannitol, like isomaltooligosaccharides, were not hydrolyzed. Regarding the
      conformation of sucrose, leucrose, and maltose previously determined by molecular
      dynamics simulations, a reasonable explanation for the different rates of
      hydrolysis could be postulated. Based on the enzyme kinetic parameters for the
      series of maltooligosaccharides, subsite affinities (A1) according to the subsite
      theory were calculated as 7.5 (A1), 17 (A2), 3.4 (A3), and 1.3 kJ/mol (A4) for
      subsites 1, 2, 3, and 4, respectively. The intrinsic rate constant k'int was
      estimated at 76 s-1.

PMID- 9633605
TI  - Structural characterization of the covalent attachment of leukotriene A3 to
      leukotriene A4 hydrolase.
AB  - Leukotriene A4 (LTA4) hydrolase catalyzes the conversion of the unstable epoxide
      LTA4 [5(S)-trans-5,6-oxido-11,14-cis-eicosatetraenoic acid] into proinflammatory
      LTB4. During the process of catalyzing this reaction, the enzyme is suicide
      inactivated by its substrate. In addition, LTA3, and analogue of LTA4 that lacks
      the C14-C15 double bond, is a potent suicide inhibitor of LTA4 hydrolase. We have
      synthesized [3H]LTA3 and used this ligand to demonstrate that LTA3 can covalently
      label LTA4 hydrolase and that this labeling is specifically competed for by
      bestatin and LTA4. Incubation of recombinant human LTA4 hydrolase with LTA3
      followed by proteolysis (endoproteinase Lys-C) resulted in a peptide map with a
      single modified peptide defining the location of the LTA3 covalent attachment
      region. This modified 21-amino-acid peptide had a UV absorption spectrum
      corresponding to a conjugated triene chromophore which established conservation
      of this structural unit after covalent interaction of LTA3 with LTA4 hydrolase.
      MALDI-TOF mass spectrometric analysis of the 21-amino-acid peptide adduct
      revealed an abundant MH+ at m/z 2658, consistent with the predicted nominal mass
      of the sequenced peptide with the addition of a single LTA3 moiety. Proteolysis
      of LTA4 hydrolase modified with LTA3 was performed sequentially with endo-Asp-N
      and endo-Lys-C. The resulting peptide isolated by reverse-phase high-performance
      liquid chromatography was analyzed by mass spectroscopy revealing two related
      peptides, D371-K385 (m/z 2018.0) and D375-K385 (m/z 1577.8), both of which
      retained the elements of LTA3. Postsource decay of m/z 1577.8 resulted in an
      abundant ion at m/z 536 and an ion of lesser abundance at m/z 856 consistent with
      cleavage between V381 and P382 that supported assignment of the modified tyrosine
      residue at Y383. These results suggest nucleophilic attack of a tyrosine residue
      (Y383) at the conjugated triene epoxide of LTA3 resulting in a triene ether
      carbinol covalent adduct.

PMID- 9633606
TI  - Tungstate: a potent inhibitor of multifunctional glucose-6-phosphatase.
AB  - The insulin-like action of tungstate in diabetic rats (A. Barbera et al., 1994,
      J. Biol. Chem. 269, 20047-20053) prompted us to examine the effects of tungstate
      on the glucose-6-phosphatase system. Our results indicate that tungstate is a
      potent inhibitor of glucose-6-phosphatase, with a Ki in the 10-25 microM range
      determined with native microsomes and in the 1-7 microM range determined with
      detergent-treated microsomes. With both preparations, simple linear competitive
      inhibition was observed versus glucose 6-phosphate (glucose-6-P) as substrate
      with the glucose-6-P phosphohydrolase activity of the enzyme. Tungstate was a
      simple linear competitive inhibitor versus carbamyl phosphate (carbamyl-P) and a
      linear noncompetitive inhibitor versus glucose with the carbamyl-P:glucose
      phosphotransferase activity of the glucose-6-phosphatase system. These findings,
      in addition to the observation that tungstate protected the enzyme against
      thermal inactivation, indicate that tungstate binds with high affinity and
      competes at the active site of the enzyme where the substrates glucose-6-P and
      carbamyl-P bind prior to catalysis. Our results suggest that potent inhibition of
      glucose-6-P hydrolysis by tungstate is likely responsible, at least in part, for
      the normalization of glycemia and the rebound in hepatic glucose-6-P levels
      observed in earlier studies in which tungstate exhibited insulin-like action in
      diabetic rats.

PMID- 9633607
TI  - Semisynthetic flavocytochromes based on cytochrome P450 2B4: reductase and
      oxygenase activities.
AB  - A synthetic flavocytochrome with the reductase and oxygenase activities was
      obtained by covalent binding of riboflavin to cytochrome P450 2B4. The reactions
      catalyzed by the newly synthesized flavocytochromes were studied. Formation of
      carbon monoxide complex with the reduced form of hemoprotein led to 60-80%
      inhibition of oxygenase reactions, indicating the leading role of reduced heme
      iron in generating active oxygen species by flavocytochromes.

PMID- 9633608
TI  - Quantitative trait loci on chromosomes 1 and 4 affect lipid phenotypes in the
      rat.
AB  - The spontaneously hypertensive rat (SHR/Mol) and the spontaneously diabetic BB/OK
      rat were crossed, and the F1 hybrids were backcrossed onto the BB/OK rat in order
      to search for quantitative trait loci (QTL) affecting serum total cholesterol and
      triglycerides on chromosomes 1, 3, 4, 10, 13, 18, and X. On chromosome 4 a QTL
      for triglyceride levels (lod score 3.3) was found within the region flanked by
      the D4Mit9 and Il-6 markers. Suggestive linkage (lod score 1.9) was found for
      total cholesterol on chromosome 4 at the Spr locus. Also, on chromosome 1
      suggestive linkage for both investigated traits was found at marker D1Mit14 (lod
      score 1.9 for triglycerides, 2.1 for total cholesterol). The results of the study
      could contribute to the explanation of the genetic basis of lipid abnormalities,
      which are a common feature of pathological disorders such as coronary heart
      disease, hypertension, or non-insulin-dependent diabetes.

PMID- 9633609
TI  - Exocytotic stimulation promotes association of the ADP-ribosylation factor with
      PC12 cell membranes.
AB  - ADP-ribosylation factors (ARFs) are a family of small molecular, monomeric GTP
      binding (G) proteins, initially identified by their ability to enhance cholera
      toxin (CTX) ADP-ribosyltransferase activity. ARFs have been implicated in protein
      transport and vesicle and endosome fusion. Although several reports show that
      synthetic peptides of the N-terminus of ARF inhibited Ca(2+)-dependent exocytosis
      in permeabilized adrenal chromaffin cells, the role of ARFs in exocytosis has not
      been established. In this study, we investigated the translocation of ARFs to the
      membrane fraction from the cytosol fraction in PC12 cells after exocytotic
      stimulation by measuring the immunoreactivity of ARFs (with anti-ARF anti-serum
      and with anti-ARF3 antibodies) and enzymatic ARF activity, which enhances the CTX
      effect. Both the immunoreactivity and the enzymatic activity of ARF in the
      membrane fraction increased about twofold, significantly, after exocytotic
      stimulation with ATP and KCl. The translocation of ARF and noradrenaline release
      was observed in the presence of extracellular CaCl2, but not in the absence of
      CaCl2. The ARF translocated to the membrane fraction after stimulation in intact
      cells seemed to be an inactive, perhaps is the GDP form, because ARF did not
      activate CTX in the absence of guanosine 5'-O-(thiotriphosphate) (GTP gamma S).
      As previously reported, ARF in the active, GTP gamma S-bound state bound to the
      membrane fractions. Thus ARF may have been active during translocation and
      inactivated later. The immunoreactivity of Gs alpha, one of the trimeric G
      proteins, was not changed before or after stimulation. These findings suggest
      that ARFs translocate to membranes from the cytosolic fraction after exocytotic
      stimulation in PC12 cells, and raise the possibility that ARFs regulate
      exocytosis.

PMID- 9633610
TI  - 3,5,3'-triiodothyronine induces mitochondrial permeability transition mediated by
      reactive oxygen species and membrane protein thiol oxidation.
AB  - Ca(2+)-loaded rat liver mitochondria treated with 3,5,3'-triiodothyronine (T3)
      undergo nonspecific inner membrane permeabilization, as evidenced by
      mitochondrial swelling, a decrease in membrane potential (delta psi), and an
      increase in the rate of oxygen uptake. T3 analogues thyroxine (T4), 3',5'
      diiodothyronine (T2), and 3,5',3'-triiodothyronine (reverse T3), in decreasing
      order of potency, resulted in a similar but less extensive effect.
      Permeabilization induced by T3 is dependent on Ca2+ (1 microM) and T3 (0.5-25
      microM) concentrations and is inhibited by cyclosporin A, a known inhibitor of
      mitochondrial permeability transition. Catalase or dithiothreitol also prevents
      membrane permeabilization, suggesting the participation of membrane protein thiol
      group oxidation induced by reactive oxygen species. The determination of the
      mitochondrial membrane protein thiol group content after treatment with Ca2+ and
      T3 shows a significant decrease, due to thiol oxidation. When mitochondria are
      incubated in the presence of inorganic phosphate and the protonophore carbonyl
      cyanide p-trifluoromethoxyphenylhydrazone, mitochondrial swelling still occurs
      after treatment with T3 and high Ca2+ concentrations, suggesting that
      mitochondrial permeabilization is not dependent on T3-induced delta psi or matrix
      pH alterations. Under these experimental conditions, when no oxygen is present in
      the incubation medium, no permeabilization occurs, suggesting that the
      permeabilization is dependent on mitochondrial-generated reactive oxygen species.
      Confirming this hypothesis, superoxide generation in a suspension of
      submitochondrial particles is increased when T3 is present. Our results lead to
      the conclusion that T3 induces a situation of oxidative stress in isolated liver
      mitochondria, with Ca(2+)-mediated membrane protein thiol oxidation and
      nonspecific inner membrane permeabilization.

PMID- 9633612
TI  - Evidence for a protein-protein complex during iron loading into ferritin by
      ceruloplasmin.
AB  - The formation of a protein-protein complex for the loading of iron into ferritin
      by ceruloplasmin was investigated. Ferritin stimulated the ferroxidase activity
      of ceruloplasmin unless the ferritin was fully loaded, in which case it inhibited
      the ferroxidase activity of ceruloplasmin. The apparent association constant for
      the interaction of ferritin and ceruloplasmin was 24 nM. Isothermal titration
      calorimetry indicated that the interaction of ceruloplasmin and ferritin was
      endothermic, driven by positive changes in entropy. The association constants for
      complex formation between ferritin and ceruloplasmin were 4.5 +/- 0.7 x 10(5) and
      9.5 +/- 0.3 x 10(4) M-1 for the reduced and oxidized forms of ceruloplasmin,
      respectively. The oxidized form of ceruloplasmin was retained on an affinity
      column with ferritin immobilized as the ligand and remained bound to the column
      with mobile phases of increased hydrophobicity, but was eluted with increased
      ionic strength. The ability of ceruloplasmin to remain bound to the affinity
      resin was affected by the species from which ceruloplasmin was isolated. Gradient
      ultracentrifugation also provided evidence that the two proteins were associated,
      since ferritin promoted migration of ceruloplasmin through the gradient.
      Including ferrous iron in the gradient resulted in reduction of ceruloplasmin and
      increased the mobility of ceruloplasmin with ferritin. These data provide
      evidence that ferritin and ceruloplasmin form a protein-protein complex during
      iron loading into ferritin, which may limit redox cycling of iron in vivo.

PMID- 9633611
TI  - Cross-linking and disulfide bond formation of introduced cysteine residues
      suggest a modified model for the tertiary structure of URF13 in the pore-forming
      oligomers.
AB  - URF13 is a mitochondrially encoded protein in the inner mitochondrial membrane of
      maize (Zea mays L.) carrying the cms-T cytoplasm. This protein is responsible for
      Texas-type cytoplasmic sterility and is a ligand-gated, pore-forming receptor for
      the pathotoxins of fungal pathogens Bipolaris maydis race T and Phyllosticta
      maydis. URF13 contains three transmembrane alpha-helices, with amphipathic
      helices II and III likely involved in pore formation, and is present as oligomers
      in cms-T maize mitochondria and when expressed in Escherichia coli cells. To
      study tertiary and quaternary structures of URF13 oligomers, we employed
      combinations of site-directed mutagenesis and chemical cross-linking. We
      introduced Cys residues individually into consecutive positions 78-82, believed
      to be in helix III. We expressed these proteins in E. coli cells and tested for
      cross-linking through disulfide bond formation or by using Cys-Cys cross-linkers.
      URF13-R79C, URF13-R81C, and URF13-T82C were cross-linked using Cys-Cys-specific
      cross-linkers, as were double mutants URF13-C27R/R79C, URF13-C27R/R81C, and URF13
      C27R/T82C, indicating that the cross-linking was between introduced Cys residues
      on adjacent URF13 molecules. Disulfide bond formation, induced by diamide, was
      seen only in URF13-T82C and URF13-C27R/T82C, indicating that Cys residues
      introduced into position 82 are closely juxtaposed in the oligomers. Based on
      these observations, we modified the models for the secondary structure of URF13
      and the tertiary structure of the URF13 oligomers. Sequential cross-linking of
      URF13-R81C oligomers with bismaleimidohexane (Cys-Cys cross-linker) and N,N'
      dicyclohexylcarbodiimide (Lys-Asp/Glu cross-linker) suggests that URF13 oligomers
      consist of an even number of monomers.

PMID- 9633613
TI  - Osmolyte strategy in human monocytes and macrophages: involvement of p38MAPK in
      hyperosmotic induction of betaine and myoinositol transporters.
AB  - Betaine and myoinositol are compatible organic osmolytes which are specifically
      accumulated by cells exposed to hyperosmotic medium. A role for compatible
      organic osmolytes in the regulation of immune function for rat liver macrophages
      has been described recently. This report describes an osmolyte strategy in human
      peripheral blood monocytes and human peripheral blood-derived macrophages.
      Hyperosmotic (405 mOsm) exposure of monocytes and macrophages led to an
      upregulation of betaine/gamma-amino-n-butyric acid (GABA) transporter BGT-1 and
      sodium-dependent myoinositol transporter SMIT in mRNA levels within 6 to 12 h.
      Induction of BGT-1 and SMIT mRNA occurred regardless of whether hyperosmolarity
      was induced by addition of NaCl (50 mM) or raffinose (100 mM). Betaine (5 mM)
      inhibited upregulation of BGT-1 as well as SMIT mRNA. After hyperosmotic (405
      mOsm) exposure uptake of betaine and myoinositol was increased up to 10-fold
      compared to normoosmotic conditions. Hypoosmotic exposure led to a rapid efflux
      of betaine and myoinositol. Treatment of cells with the pyridinyl imidazole SB
      203580 (10 microM), a specific inhibitor of p38 MAP kinase, inhibited the
      hyperosmolarity-induced increase in BGT-1 and SMIT mRNA as well as betaine and
      myoinositol uptake by 45-70%. The data show that human peripheral blood monocytes
      and human peripheral blood-derived macrophages use betaine and myoinositol are
      compatible organic osmolytes when exposed to osmotic stress and that p38MAPK is
      involved in hyperosmolarity-induced upregulation of osmolyte transporters BGT-1
      and SMIT.

PMID- 9633614
TI  - Involvement of the mevalonic acid pathway and the glyceraldehyde-pyruvate pathway
      in terpenoid biosynthesis of the liverworts Ricciocarpos natans and Conocephalum
      conicum.
AB  - The incorporation of 13C-labeled glucose into borneol, bornyl acetate, the
      sesquiterpenes cubebanol and ricciocarpin A, phytol, and stigmasterol has been
      studied in axenic cultures of the liverworts Ricciocarpos natans and Conocephalum
      conicum. Quantitative 13C NMR spectroscopic analysis of the resulting labeling
      patterns showed that the isoprene building blocks of the sesquiterpenes and
      stigmasterol are built up via the mevalonic acid pathway, whereas the isoprene
      units of the monoterpenes and the diterpene phytol are exclusively derived from
      the glyceraldehyde-pyruvate pathway. These results indicate the involvement of
      both isopentenyl diphosphate biosynthetic pathways in different cellular
      compartments.

PMID- 9633615
TI  - Guinea pig liver Mu-class glutathione S-transferase M1-2 cross-reacts with
      antibodies to both rat Mu- and theta-class glutathione S-transferases.
AB  - Two novel major heterodimeric Mu-class glutathione (GSH) S-transferases (GSTs),
      designated M1-2 and M1-3*, were isolated from guinea pig (gp) liver cytosol and
      purified to homogeneity together with a known major homodimeric Mu-class gpGSTM1
      1 (reported as GST b by R. Oshino, K. Kamei, M. Nishioka, and M. Shin, 1990, J.
      Biochem. 107, 105-110). These three gpGSTs were quantitatively retained on an S
      hexyl-GSH affinity column and separated as homogeneous proteins by
      chromatofocusing. Subunits of the heterodimers were inseparable on sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis, but could be completely separated by
      reverse-phase partition high-performance liquid chromatography. A molecular
      cloning study demonstrated that the gpGST subunit M2 consisted of 217 amino acid
      residues with a calculated molecular mass of 25,562 and shared 84% identity in
      overall amino acid sequence with gpGSTM1-1. N-terminal amino acid sequences of
      peptides from the gpGST subunit M3* with a blocked N-terminus strongly suggested
      that it should belong to the Mu class. Western blot analysis using antisera
      raised against purified rat (r) GSTsA1-2 (Alpha), M1-1, P1-1 (Pi), and T2-2
      (Theta) indicated that gpGSTsM1-1 and M1-3* cross-reacted only with anti-rGSTM1
      antibody. However, gpGSTM1-2 cross-reacted intensely to almost the same extent
      with antibodies to both rGSTsM1-1 and T2-2. A homodimeric gpGSTM2-2, artificially
      constructed from native gpGSTM1-2 by treatment with guanidine hydrochloride
      followed by dialysis, intensely cross-reacted with antibodies to both the rat Mu-
      and Theta-class GSTs. Thus, the gpGST subunit M2 provided the first evidence for
      the double immuno-cross-reaction of a GST with polyclonal antibodies to two
      different classes of GSTs.

PMID- 9633617
TI  - [Use of the micronucleus test in the evaluation of cytogenetic state of persons
      living in the polluted area of the Siberian chemical plant].
AB  - We have carried out analysis of the number of blood erythrocytes and lymphocytes
      with micronuclei in the inhabitants of four settlements located near the place of
      the accident, which happened at the atomic power station of the Siberian chemical
      plant (Tomsk-7) on April 6, 1993. In all cases, the people examined showed a
      considerable increase in the number of cells with micronuclei as compared with
      the control. We observed the same people for two years and found a gradual
      decrease in the number of cells with micronuclei. It has been shown in this work,
      that people born in 1963-1970 have a much higher level of cells with micronuclei,
      which we tend to regard as a result of the radiation accident at the Siberian
      chemical plant in 1963. The data we have obtained allow us to conclude that
      penetration of radionuclides into the human organism in the prenatal and early
      postnatal periods can lead to the formation of stable clones of erythroid cells
      with micronuclei and a higher level of erythrocytes with micronuclei, which can
      remain in the blood for a long time.

PMID- 9633616
TI  - [Interactions of inhibitor of free radical reactions and 2-deoxyribosyl
      macroradicals].
AB  - By steric computer modelling of five types of 2-deoxyribosyl radicals and their
      molecular products generated in DNA by radiation as a result of R + InH = RH + In
      reaction the displacement of DNA bases (maximum--for C'1 atoms and minimum for
      C'3 ones) has been determined. Literature data on the DNA decay in the irradiated
      cells, and in DNA frozen solutions as well as the data on radiolysis of compounds
      modelling separate DNA fragments allowed to offer a general scheme of the every 2
      deoxyribosyl radical transformation and to calculate a balance between the
      intermediate and final molecular products (processes) of the 2-deoxyribosyl
      radiolysis. The DNA conformation change due to the 2-deoxyribosyl stereoisomers
      formation at C'3 and C'4 atoms is discussed as one of the suggested reasons for
      genetic radiation mutation.

PMID- 9633618
TI  - [Determination of mutation frequency at loci of glycophorin A and T-cell
      receptors: informativeness for biological dosimetry of acute and prolonged
      irradiation].
AB  - The frequencies of somatic mutations at loci of glycophorin A (GPA) and T-cell
      receptor (TCR) were determined in persons exposed professionally to ionizing
      radiation or a result of accidents at nuclear power plants and in control donors.
      Dependence of glycophorin A mutant (NO) cell frequency on doses of acute (up to
      3.5 Gy) and prolonged (up to 15.0 Gy) irradiation was shown. The slope of linear
      regression corresponded to increase of NO-mutant frequency by 31.1 x 10(-6)/Gy (r
      = 0.87, p < 0.0001) for acute irradiation and by 6.3 x 10(-6)/Gy (r = 0.61, p <
      0.0001) for prolonged one. The 5-fold decrease of the linear regression slope in
      the case of prolonged irradiation makes significantly worse permissive ability of
      the GPA test. Therefore its use for biological dosimetry of prolonged irradiation
      is not expedient in dose interval up to 1 Gy. The frequency of mutations in genes
      of T-cell receptor significantly correlated with dose of irradiation only in
      group of donors with recent radiation exposure (r = 0.75, p = 0.0002). Meanwhile,
      the TCR method is more sensitive and informative for biological dosimetry of
      recent radiation, than the GPA test.

PMID- 9633622
TI  - [Effects of prolonged gamma irradiation and hypoxia on bioelectrical activity of
      myocardial cells].
AB  - It was established that prolonged gamma-irradiation of rats leads to the decrease
      of amplitude and duration of action potentials of right atrial cells, attenuation
      of the dependence of these electrophysiological characteristics upon the
      stimulation frequency, depression of the interval of cardiomyocytes reaction on
      the hypoxia. The revealed post-radiation changes determine the reduction of
      function resistance of heart cells bioelectrical activity and promote the
      initiation of arrhythmias.

PMID- 9633619
TI  - [Determination of mutation frequency at loci of glycophorin A and T-cell
      receptor: study of Chernobyl AES accident cleanup workers].
AB  - The frequencies of somatic mutations at loci of glycophorin A (GPA) and T-cell
      receptor (TCR) were determined in control unexposed donors and Chernobyl clean up
      workers, who received low doses of irradiation up to 0.25 Gy. High variability of
      mutant rates for two investigated genes was shown in the clean up workers. No
      significant difference in the GPA (NO) mutant frequencies was observed between
      the clean up workers and control donors (p > 0.05), though there is a tendency
      for increasing the GPA mutation rate in the clean up workers. Meanwhile, the TCR
      mutation rate was significantly increased the clean up workers (p < 0.01),
      perhaps because of acceleration of spontaneous mutagenesis and possible genome
      instability. Persons with elevated levels of mutations at two loci can present a
      group at high risk in respect to oncological diseases.

PMID- 9633621
TI  - [Morphological characteristics of central and peripheral organs of rat immune
      system in time course of adaptation to external low-dose gamma irradiation].
AB  - The morphohistochemical changes in immune system lymphoid organs and skin of
      rats, exposed to single and fractionated gamma-radiation (0.35 Gy) were studied
      during 1 month. It has been revealed that single irradiation didn't significantly
      influence, while the fractionated irradiation in equal dose resulted in lymphoid
      cells elimination from thymus and spleen and changes in skin and bone marrow
      cells subsets, inducing the increase of lymphoid cells number and activation of
      tissue basophils and macrophages reaction.

PMID- 9633620
TI  - [Study of physical properties of the apical membrane of enterocytes of rat small
      intestine under the effects of ionizing radiation].
AB  - The effect of X-ray radiation in doses of 1.0 and 3.0 Gy (1 day after
      irradiation) on physical properties of the apical membrane of rat small intestine
      enterocytes is studied. It is shown that the fluidity of the bulk lipids doesn't
      change but the fluidity of the boundary lipids increases after irradiation. The
      data on quenching of the tryptophane fluorescence by pyrene and magnesium ions
      indicates apparently the irradiation--induced protein aggregation in membrane.

PMID- 9633625
TI  - [Forming of memory (imprinting) in chicks after prior low-level exposure to
      electromagnetic fields].
AB  - EMF of power density from 0.4 to 10 mW/cm2 can influence forming the memory
      (imprinting). Showed the possibility to fix EMF modulated in embryonic brain
      during the natal period and conservation of this information after birth.

PMID- 9633624
TI  - [Study of immune status indices, levels of alpha-1-thymosin and autoantibodies to
      thymic epithelial cells in persons who worked in the 30-kilometer zone of the
      Chernobyl AES depending on the radiation dose].
AB  - The indices of immune status, concentration of alpha 1-thymosin and level of
      thymus epithelial cell autoantibodies in human blood of persons, who had worked
      in 30-km zone Chernobyl NPP were studied. The decrease in mean number of
      leukocytes, lymphocytes, CD5+, CD4+, CD8+ cells, content of serum alpha 1
      thymosin and increased level of autoantibodies were detected in workers, whose
      dose rates irradiation were greater than 25 cSv. So, the quality differences in
      the changes of immune system, which were induced by low dose chronic irradiation
      were obtained.

PMID- 9633623
TI  - [Hemo- and immunostimulating effect of an extract from blood cells of the Central
      Asian tortoise].
AB  - Radiotherapeutic efficacious of the compounds from major organs and tissues of
      Central Asian tortoise--the animal known for its unique radioresistance, has been
      checked up. Along with the so well-known compounds as the plasma ones, tortoise
      spleen extracts (TSE) and the ones from the liver of adult animals and embryos,
      extracts from kidneys and muscles have been shown to increase the survivability
      rate of irradiated rats and mice. The compound, that called "Tortezin" shows the
      highest blood cell cytosol effect. The specific activity and the output are 4 and
      12 times higher, than the ones of TSE, respectively. Dose increase factor (DIF)
      reaches as far as 1.41. The compound possesses considerable immunostimulating
      activity. The detailed physico-chemical characteristics of the compound, quite
      sufficient for its identification has been made.

PMID- 9633626
TI  - [Features of modifications of cytotoxic consequences of microwave and thermal
      heating].
AB  - The incubation of bacteria Escherichia coli B/r and Escherichia coli Bs-1,
      preliminarily heated by microwave (frequency 7 GHz) or equal usual heat in water
      isotonic (0.9%) or hypertonic (10%) solution of sodium chloride resulted in
      decrease or increase of the cell lethality independently from heating manner.
      Hypertonic solutions of this compound, as was established, protected the cells
      against heat damages during the microwave heating less effectively than during
      thermal heating.

PMID- 9633627
TI  - [Biomedical and economic consequences of stratosphere ozone depletion].
AB  - Information on possible human health-changes associated with stratosphere ozone
      depletion and amplification factor (% increase of the stick rate by 1% decrease
      of ozone) values for acute (erythema, keratitis, cataract, immunosuppression) and
      chronic (skin cancer, cataract) effects of natural UV-radiation was analysed.
      Amplification factor (AF) values for acute UV-effects increase with degree of
      ozone depletion. For degrees less than 12.5% they are independent of latitude and
      equal to 1.9 for erythema, 1.3-1.5 for keratitis, 1.7-2.3 for cataract and 0.9
      1.1 for immunosuppression. AF values for incidence of non-melanoma skin cancer
      are independent of age, higher in males than females, and higher for squamous
      cell carcinoma, than for basal cell carcinoma. Their optimal estimations for
      whites equal to 2.7 for basal cell and 4.6 for squamous cell carcinoma. AF values
      for incidence of cutaneous malignant melanoma range between 1 and 2, for melanoma
      mortality--between 0.3 and 2. AF values for incidence of cataract range between
      0.3 and 1.2 with optimal estimations between 0.6 and 0.8. Prognosis of non
      melanoma skin cancer and cataract incidences, melanoma mortality and economic
      loss for different scenarios of stratosphere ozone depletion are presented.

PMID- 9633628
TI  - [Dynamics of decrease of the transfer coefficient of Cs-137 to agricultural
      plants after the Chernobyl AES accident].
AB  - Data on the dynamics of the decrease of 137Cs transfer factors to agricultural
      plants after the accident at the ChNPP are presented. The ecological half-life
      periods of decrease in transfer factors in the first period after the accident
      (1987-1989) have been shown to vary between 1.2 and 2.9 years. Subsequently the
      decrease slowed down and in 1990-1994 the half-life periods amounted to 4-11
      years depending on plant species peculiarities and soil properties.

PMID- 9633629
TI  - Histidine carboxylase of Leuconostoc oenos 9204: purification, kinetic
      properties, cloning and nucleotide sequence of the hdc gene.
AB  - Histidine decarboxylase (HDC) was purified to homogeneity from Leuconostoc oenos
      9204, a wine lactic acid bacterium. Histidine decarboxylase comprised two
      subunits, respectively alpha and beta. The hdc gene was cloned and sequenced. The
      gene encodes a single polypeptide of 315 amino acids, demonstrating that Leuc.
      oenos 9204 HDC was synthesized as a precursor proHDC pi 6 (Mr 205,000). A
      cleavage between Ser-81 and Ser-82 generated the alpha (Mr 25,380) and beta (Mr
      8840) chains, which suggested that the holoenzyme exists as a hexameric structure
      (alpha beta)6. At the optimal pH of 4.8, the HDC activity exhibited a simple
      Michaelis-Menten kinetic (K(m) = 0.33 mmol l-1, Vmax = 17.8 mumol CO2 min-1 mg
      1), while at pH 7.6 it was sigmoidal (cooperativity index of 2). Histamine acted
      as a competitive inhibitor (Ki = 32 mmol l-1). The similarities of these results
      with those described for other bacterial HDC support the assumption that the
      pyruvoyl enzymes evolved from a common ancestral protein and have similar
      catalytic mechanisms. These results also confirmed that the main lactic acid
      bacterial species responsible for malolactic fermentation in red wine is able to
      produce histamine. Bacteria carrying the HDC activity must be avoided during
      selection of strains for the production of malolactic starters.

PMID- 9633630
TI  - The effect of essential oils of basil on the growth of Aeromonas hydrophila and
      Pseudomonas fluorescens.
AB  - Basil essential oils, including basil sweet linalool (BSL) and basil methyl
      chavicol (BMC), were screened for antimicrobial activity against a range of Gram
      positive and Gram-negative bacteria, yeasts and moulds using an agar well
      diffusion method. Both essential oils showed antimicrobial activity against most
      of the micro-organisms examined except Clostridium sporogenes, Flavimonas
      oryzihabitans, and three species of Pseudomonas. The minimum inhibitory
      concentration (MIC) of BMC against Aeromonas hydrophila and Pseudomonas
      fluorescens in TSYE broth (as determined using an indirect impedance method) was
      0.125 and 2% (v/v), respectively; the former was not greatly affected by the
      increase of challenge inoculum from 10(3) to 10(6) cfu ml-1. Results with resting
      cells demonstrated that BMC was bactericidal to both Aer. hydrophila and Ps.
      fluorescens. The growth of Aer. hydrophila in filter-sterilized lettuce extract
      was completely inhibited by 0.1% (v/v) BMC whereas that of Ps. fluorescens was
      not significantly affected by 1% (v/v) BMC. In addition, the effectiveness of
      washing fresh lettuce with 0.1 or 1% (v/v) BMC on survival of natural microbial
      flora was comparable with that effected by 125 ppm chlorine.

PMID- 9633631
TI  - Immunodot detection of nisin Z in milk and whey using enhanced chemiluminescence.
AB  - A highly specific antisera was produced in New Zealand white rabbits against
      nisin Z, a 3400 Da bacteriocin produced by Lactococcus lactis ssp. lactis biovar.
      diacetylactis UL 719. A dot immunoblot assay was then developed to detect nisin Z
      in milk and whey. As few as 1.5 10(-1) international units per ml (IU ml-1),
      corresponding to 0.003 microgram ml-1 of pure nisin Z, were detected in carbonate
      bicarbonate buffer within 6 h using chemiluminescence. When milk and whey samples
      were tested, approximately 0.155 microgram ml-1 (7.9 IU ml-1) of nisin Z was
      detected. The detection limit obtained was lower than that of traditional methods
      including microtitration and agar diffusion.

PMID- 9633632
TI  - Mathematical modelling of the heat resistance of Listeria monocytogenes.
AB  - The heat resistance of Listeria monocytogenes phagovar
      2389/2425/3274/2671/47/108/340 (1992 French outbreak strain) in broth was studied
      at 55, 60 and 65 degrees C. Experiments were carried out on bacterial cultures in
      three different physiological states: cultures at the end of the log phase,
      cultures heat-shocked at 42 degrees C for 1 h, and subcultures of cells resistant
      to prolonged heating. Survivor curves were better fitted using a sigmoidal
      equation than the classical log-linear model. This approach was justified by the
      existence of heat resistance distributions within the bacterial populations.
      Peaks (log10 of heating time) of heat resistance distributions of untreated, heat
      shocked, and selected cultures at 55, 60 and 65 degrees C were 0.34, -0.90 and 
      1.84 min, 0.74, -0.51 and -1.24 min, and 0.17, -0.94 and -1.45 min, respectively.
      The widths of the distributions are proportional to 0.29, 0.36 and 0.41 min0.5,
      0.26, 0.36 and 0.41 min0.5, and 0.34, 0.44 and 0.41 min0.5. An increase in the
      thermal tolerance could then be induced by sublethal heat shock or by selection
      of heat resistant cells.

PMID- 9633635
TI  - Sensitivity of food pathogens to garlic (Allium sativum).
AB  - The inhibitory activity of garlic (Allium sativum) against Staphylococcus aureus,
      Salmonella typhi, Escherichia coli and Listeria monocytogenes was measured by the
      'turbidity' method. Minimum inhibitory concentration (MIC) of garlic at 80%
      inhibition level was calculated for these bacteria. All bacterial pathogenic
      strains tested were inhibited by garlic; E. coli was most sensitive and Listeria
      monocytogenes was least sensitive. Therefore, garlic has potential for the
      preservation of processed foods.

PMID- 9633634
TI  - QSARs for the effect of benzaldehydes on foodborne bacteria and the role of
      sulfhydryl groups as targets of their antibacterial activity.
AB  - Quantitative structure activity relationships (QSARs) were obtained describing
      the activity of a series of benzaldehydes against three different foodborne
      bacteria, Listeria monocytogenes F6861, serotype 4b, Salmonella enteritidis,
      Phage type 4, P167807 and Lactobacillus plantarum INT.L11. MIC values at pH 6.2
      and 35 degrees C were obtained for 11 phenolic benzaldehydes to produce multiple
      linear regression and artificial neural network models. For each organism, the
      models contained a steric parameter Vw and an electronic-steric parameter for
      ortho substituents Es degree. The benzaldehydes did not require to partition to
      produce their effect, shown by the lack of a lipophilic parameter in the models.
      This strongly suggests that they act on the outside of the cells. Substitution
      ortho to the carbonyl group increased their antibacterial action. Cells were
      treated with 2,3-dihydroxy benzaldehyde and examined for their ability to bind
      radiolabelled iodoacetate to envelope sulfhydryl groups that remained available.
      It was shown that the accumulation of radiolabelled iodoacetate was lower after
      treatment, indicating possible competition between these two compounds for the
      same target. The order of the sensitivity to benzaldehydes (Salmonella > Listeria
      > Lactobacillus) correlated with the number of surface sulfhydryl groups
      available, being highest for Salmonella.

PMID- 9633637
TI  - Colonization of Vibrio pelagius and Aeromonas caviae in early developing turbot
      (Scophthalmus maximus L.) larvae.
AB  - Polyclonal antisera made in rabbits against whole washed cells of Vibrio pelagius
      and Aeromonas caviae were used for detection of these bacterial species in the
      rearing water and gastrointestinal tract of healthy turbot (Scophthalmus maximus)
      larvae exposed to V. pelagius and/or Aer. caviae. The results demonstrated that
      this method is suitable for detection of V. pelagius and Aer. caviae in water
      samples and larvae at population levels higher than 10(3) ml-1 and 10(3) larva-1.
      Populations of aerobic heterotrophic bacteria present in the gastrointestinal
      tract of turbot larvae, estimated using the dilution plate technique, increased
      from approximately 4 x 10(2) bacteria larva-1 on day 3 post-hatching to
      approximately 10(5) bacteria fish-1 16 days post-hatching. Sixteen days after
      hatching, Vibrio spp. accounted for approximately 3 x 10(4) cfu larva-1 exposed
      to V. pelagius on days 2, 5 and 8 post-hatching. However, only 10(3) of the
      Vibrio spp. belonged to V. pelagius. When larvae were exposed to Aer. caviae on
      day 2 post-hatching, the gut microbiota of 5-day old larvae was mainly colonized
      by Aeromonas spp. (10(4) larva-1), of which 9 x 10(3) belonged to Aer. caviae.
      Later in the experiment, at the time when high mortality occurred, 9 x 10(5) Aer.
      caviae were detected. Introduction of V. pelagius to the rearing water seemed to
      improve larval survival compared with fish exposed to Aer. caviae and with the
      control group. It was therefore concluded that it is beneficial with regard to
      larval survival to introduce bacteria (V. pelagius) to the rearing water.

PMID- 9633638
TI  - Heat resistance of Listeria monocytogenes in dairy products as affected by the
      growth medium.
AB  - Listeria monocytogenes strains 1151 and Scott A were grown in broth at 30 degrees
      C and transferred to half cream, double cream and butter stored at 5 degrees C to
      determine the influence of dairy product composition on heat resistance at 52,
      56, 60, 64 and 68 degrees C. Strain 1151 showed a higher heat resistance than
      strain Scott A. The heat resistance of both strains was higher in the dairy
      products than in broth, particularly at lower temperatures. A significant
      difference was observed between log 10 of the D-values in the different dairy
      products. The D-values obtained for both strains resuspended in all the dairy
      products would result in efficient elimination of the pathogen at 72.7 degrees C
      for 15 s. The highest D-value was 11.30 s at 68 degrees C and by using a z-value
      of 6.71 degrees C it can be determined that at 72.7 degrees C the D-value would
      be 1.5 s. The 15 s process would therefore achieve 10 log reductions. The effect
      of growth conditions on the heat resistance at 60 degrees C of L. monocytogenes
      Scott A was also investigated. When the cells were grown in the diary products
      themselves, and particularly butter, the heat resistance of Scott A was enhanced;
      for example, the D-values were 7.15 times higher than in broth. Further studies
      are required to investigate if this protection against heating exists at higher
      temperatures, in which case the efficiency of pasteurization treatments or other
      heat treatments would be considerably lowered.

PMID- 9633640
TI  - Polymorphism of Listeria monocytogenes and Listeria innocua strains isolated from
      short-ripened cheeses.
AB  - Thirty isolates of Listeria monocytogenes and 18 of L. innocua obtained from
      different short-ripened cheeses manufactured in Asturias (northern Spain), were
      compared with each other and with reference strains using serotype, phage type
      and pulsed-field restriction endonuclease digestion profiles analysis of the
      total DNA. Restriction enzymes ApaI and SmaI defined five clusters in L.
      monocytogenes (m1 to m5) and two main clusters in L. innocua (i1 and i2). Cluster
      i2 was further arranged into three subclusters (i2a, i2b and i2c) based on the
      different Eco52I (XmaIII) and Crf42I (SacII) patterns of its isolates. Clusters
      of L. innocua were clearly different whereas those of L. monocytogenes were more
      closely related to each other. In this latter species, serotype 4b isolates (m4
      and m5) constituted a more homogeneous group than serogroup I isolates (m1, m2
      and m3). Cluster m3 contained two strains of serotype 1/2a whereas m1 and m2
      harboured strains of both serotypes, 1/2a and 1/2b. Therefore, the combined use
      of restriction patterns and serotype may be useful to differentiate L.
      monocytogenes strains showing identical restriction profiles but differing in
      serotype. The cheese source of Listeria strains proved that isolates from cluster
      m1 were repeatedly detected as a contaminant in the same type of cheese.
      Comparison of L. monocytogenes ApaI profiles showed a genetic proximity of m4 and
      m5 to the recognized pathogenic strains ATCC 13932 and NCTC 11994, responsible
      for meningitis cases in other countries. Finally, bacteriophage typing data
      indicated that m4, the sole phage typable group, had a phage type resembling that
      of strains causing the Auckland (New Zealand) outbreak of listeriosis in 1969.
      These data suggest a wide distribution of closely related types which might
      cause, under several circumstances, sporadic cases of listeriosis.

PMID- 9633641
TI  - Biocidal activity in plant pathogenic Acidovorax, Burkholderia, Herbaspirillum,
      Ralstonia and Xanthomonas spp.
AB  - Antibacterial and antifungal activity was investigated for strains of Acidovorax
      spp., Burkholderia spp., Herbaspirillum rubrisubalbicans and Ralstonia
      solanacearum; strains representing 118 species and pathovars of Xanthomonas were
      also tested for phytotoxic capacity. Antibacterial activity was present in all
      Burkholderia spp. except B. andropogonis, in biovars II and III of R.
      solanacearum but not in biovars I and IV, and in two strains of Xanthomonas.
      Little antibacterial activity was recorded for Acidovorax spp. Antifungal
      activity was expressed by most strains of A. avenae ssp. avenae and A. avenae
      ssp. cattleyae. Weak or variable antifungal reactions were given by strains of A.
      avenae ssp. citrulli and no activity was expressed by A. konjaci. Most strains of
      B. caryophylli, B. cepacia, B. gladioli pv. agaricicola, B. gladioli pv.
      alliicola, B. gladioli pv. gladioli, B. glumae and B. plantari produced extensive
      inhibition zones against Rhodotorula mucilaginosa. Strains of H. rubrisubalbicans
      and R. solanacearum gave negative, weak or variable reactions. Strains of
      Xanthomonas spp. exhibited no antifungal activity. In all cases antifungal
      activity was caused by a low molecular weight toxin. Three Xanthomonas strains
      exhibited phytotoxic activity. The ecological implications of these data are
      discussed.

PMID- 9633642
TI  - Detection of pathogenic Yersinia enterocolitica using a digoxigenin labelled
      probe targeting the yst gene.
AB  - A 145 base pair digoxigenin-d-UTP-labelled probe, specific for pathogenic
      Yersinia enterocolitica heat-stable enterotoxin yst gene, was prepared by PCR.
      The probe was used in DNA-DNA colony hybridization and dot-blot hybridization
      assays. The specificity of the probe was confirmed using 52 strains representing
      all Yersinia spp., except Y. pestis. Out of a total of 25 Y. enterocolitica
      strains screened, the probe correctly identified all 18 pathogenic strains. Among
      the other Yersinia spp. screened, only one strain of Y. kristensenii was
      positively detected by the yst probe but could be differentiated by its weak
      signal response as compared with that obtained by pathogenic strains of Y.
      enterocolitica.

PMID- 9633643
TI  - Heterogeneity of plant-associated streptococci as characterized by phenotypic
      features and restriction analysis of PCR-amplified 16S rDNA.
AB  - Thirty-five strains of streptococci isolated from forage grasses were examined by
      restriction analysis of PCR-amplified 16S rDNA. Using a set of seven
      endonucleases, five 16S rDNA genotypes were obtained. The isolates could be
      identified as belonging to the species Enterococcus faecium, Ent. mundtii, Ent.
      faecalis, Ent. casseliflavus and Lactococcus lactis ssp. lactis, respectively. To
      assign the isolates to one of these species, digestion with the endonuclease
      HinfI was sufficient. Data obtained from whole-cell protein analysis were in
      accordance with the species identification. Additionally, three of the five
      species found were subdivided into two related subgroups. Both methods are
      suitable for a rapid and unequivocal identification of plant-associated
      streptococci. The phenotypic characters showed a high diversity and were in some
      cases contrary to the expected features usually given in genus and species
      descriptions. The results demonstrated the close relatedness of the determined
      species in contrast to their high phenotypic heterogeneity.

PMID- 9633645
TI  - Development of a risk assessment for BSE in the aquatic environment.
AB  - Bovine spongiform encephalopathy (BSE) is believed to be transmitted by the
      ingestion of proteinaceous agents called prions which accumulate in the brain and
      spinal cord of infected bovines. Concern has been expressed about the risks of
      transmission of BSE to humans through BSE prions discharged to the aquatic
      environment from rendering plants, abattoirs and landfills. The disease-related
      form of the prion protein is relatively resistant to degradation, and infectivity
      decays rather slowly in the environment. Levels of disinfection used for drinking
      water treatment would have little effect. This paper presents the assumptions
      which were used to model the risks from a rendering plant disposing of cull
      cattle carcasses in the catchment of a chalk aquifer which is used for a drinking
      water abstraction. The risk assessment approach focused on identifying the
      hydrogeological and physical barriers which would contribute to preventing BSE
      infectivity gaining entry to the aquifer. These barriers included inactivation of
      BSE agent by the rendering process, removal from the effluent by treatment at the
      plant, filtration and adsorption in the clay and chalk, and dilution in the
      ground water. The importance in environmental risk assessment of the cow-to-man
      species barrier is considered. Two key conclusions about the environmental
      behaviour of the BSE agent are that prion proteins are 'sticky' and bind to
      particulates, and that the millions of BSE prion molecules comprising a human
      oral ID50 are subject to some degree of dispersion and hence dilution in the
      environment. Assuming the rendering plant processes 2000 cull cattle carcasses
      per week, the risks to drinking water consumers were estimated to be remote.
      Indeed, even using worst case assumptions an individual would have to consume 21
      d-1 of tap water for 45 million years to have a 50% chance of infection through
      drinking water drawn from the aquifer.

PMID- 9633646
TI  - Radiation inactivation of some food-borne pathogens in fish as influenced by fat
      levels.
AB  - The influence of low (0.39-1.1%), medium (4.25%) and high (7.1-32.5%) fat levels
      in fish on radiation inactivation of four food-borne pathogens was investigated.
      Cells of Listeria monocytogenes 036, Yersinia enterocolitica F5692, Bacillus
      cereus and Salmonella typhimurium at logarithmic phase were inoculated in 10%
      fish homogenates and subjected to gamma irradiation at ice temperature (0-1
      degree C) with doses ranging from 0.05 to 0.8 kGy. The radiation survival curves
      of L. monocytogenes and B. cereus were characterized by shoulders, while a
      tailing effect was depicted by cells of Y. enterocolitica and B. cereus. The D10
      values in kGy calculated on the exponential part of the curve ranged from 0.2 to
      0.3, 0.15 to 0.25, 0.1 to 0.15 and 0.09 to 0.1 for L. monocytogenes 036, B.
      cereus, Salm. typhimurium and Y. enterocolitica F5692, respectively. This order
      (D10) of radiation resistance of each organism was not affected by the fat
      content of the fish. Inoculated pack studies carried out separately with each
      pathogen in fatty (Indian sardine, 7.1%) and lean (Golden anchovy, 0.39%) fish
      showed no difference in their survival after exposure to 1 kGy and 3 kGy doses,
      which corroborated the above observation. The practical significance of these
      results in the application of the technology is discussed.

PMID- 9633647
TI  - Characterization of axenic Pseudomonas fragi and Escherichia coli biofilms that
      inhibit corrosion of SAE 1018 steel.
AB  - Corrosion inhibition of SAE 1018 steel by Pseudomonas fragi and Escherichia coli
      biofilms has been evaluated using batch cultures in rich medium (LB) and seawater
      mimicking medium (VNSS) at 23 degrees C and 30 degrees C with or without daily
      medium replenishment. Biofilm components have been stained simultaneously for
      polysaccharide (calcofluor) and live and dead cells (Live/Dead Baclit viability
      kit) and visualized using confocal scanning laser microscopy (CSLM). Image
      analysis was used to quantify the relative proportions of live cells, dead cells,
      polysaccharide and void space in the biofilm. This staining technique and
      examination of the architecture of biofilms responsible for inhibiting metal
      corrosion revealed that both Ps. fragi and E. coli produce polysaccharide only in
      the seawater medium; in rich medium, the biofilm consisted mainly of a layer of
      sessile cells near the biofilm-metal interface and sparse thick clumps of cells
      at the biofilm-liquid interface. Biofilms of both strains had a higher proportion
      of live cells in the rich medium than in the seawater-mimicking medium at the
      higher temperature, and more live cells were present at the higher temperature
      for LB medium. The corrosion inhibition observed (2.3-6.9-fold in 8 d) was not
      significantly affected by medium type or replenishment. Increase in the cellular
      content of the biofilms, as a result of increasing temperature, led to a
      reduction in corrosion.

PMID- 9633648
TI  - delta-Endotoxin proteins associated with spherical parasporal inclusions of the
      four Lepidoptera-specific Bacillus thuringiensis strains.
AB  - Four Lepidoptera-specific reference strains of Bacillus thuringiensis, belonging
      to serovars sumiyoshiensis (H3a:3d), fukuokaensis (H3a:3d:3e), darmstadiensis
      (H10a:10b) and japonensis (H23), which produce spherical parasporal inclusions,
      were examined for comparative characterization of delta-endotoxins. SDS-PAGE
      profiles of the alkali-solubilized parasporal inclusions revealed the presence of
      single major protein bands of 130 kDa in the four strains. Chymotrypsin and
      trypsin treatment of the proteins gave profiles different from those of the
      strains HD-1 (serovar kurstaki, H3a:3b:3c) and T84 A1 (serovar sotto, H4a:4b).
      Also, minor variations were observed in proteolysis profiles among the four
      strains. The LC50 values of purified parasporal inclusions for the silkworm
      (Bombyx mori) larvae were 7.35, 6.45, 3.08 and 2.63 micrograms g-1 diet,
      respectively, showing that their toxicity levels were 5-15 times lower than that
      of the strain HD-1 (0.49 microgram g-1 diet). Analysis by immunodiffusion and
      immunoblotting with polyclonal antisera revealed that parasporal inclusion
      proteins of the four strains are highly related, whereas they shared few or no
      common antigens with those of the strains HD-1, T84 A1 and Buibui (serovar
      japonensis).

PMID- 9633649
TI  - Effect of glucose on glycerol metabolism by Clostridium butyricum DSM 5431.
AB  - The levels of 1,3-propanediol dehydrogenase and of the glycerol dehydrogenase in
      Clostridium butyricum grown on glucose-glycerol mixtures were similar to those
      found in extracts of cells grown on glycerol alone, which can explain the
      simultaneous glucose-glycerol consumption. On glycerol, 43% of glycerol was
      oxidized to organic acids to obtain energy for growth and 57% to produce 1,3
      propanediol. With glucose-glycerol mixtures, glucose catabolism was used by the
      cells to produce energy through the acetate-butyrate production and NADH, whereas
      glycerol was used chiefly in the utilization of the reducing power since 92-93%
      of the glycerol flow was converted through the 1,3-propanediol pathway. The
      apparent K(m)s for the glycerol dehydrogenase was 16-fold higher for the glycerol
      than that for the glyceraldehyde in the case of the glyceraldehyde-3-phosphate
      dehydrogenase and fourfold higher for the NAD+, providing an explanation for the
      shift of the glycerol flow toward 1,3-propanediol when cells were grown on
      glucose-glycerol mixtures.

PMID- 9633650
TI  - The microstructure and distribution of micro-organisms within mature Serra
      cheese.
AB  - The distribution of micro-organisms in mature Serra, a traditional Portuguese
      cheese made from unpasteurised ewes' milk without added starter culture, was
      examined by light microscopy and electron microscopy. Four populations of micro
      organisms were recognized according to their position within the cheese: (i)
      those present as apparently axenic colonies within the curd matrix; (ii) bacteria
      growing along curd junctions; (iii) yeasts and bacteria present in the smear on
      the surface of the cheese and (iv) bacteria found in cracks which penetrated the
      outer part of the cheese from the rind. Two types of crystals were observed,
      together with contaminants of vegetable origin and somatic cells originating from
      the milk.

PMID- 9633651
TI  - A new method for determining the minimum inhibitory concentration of essential
      oils.
AB  - A new microdilution method has been developed for determining the minimum
      inhibitory concentration (MIC) of oil-based compounds. The redox dye resazurin
      was used to determine the MIC of a sample of the essential oil of Melaleuca
      alternifolia (tea tree) for a range of Gram-positive and -negative bacteria. Use
      of 0.15% (w/v) agar as a stabilizer overcame the problem of adequate contact
      between the oil and the test bacteria and obviated the need to employ a chemical
      emulsifier. A rapid version of the assay was also developed for use as a
      screening method. A comparison of visual and photometric reading of the
      microtitre plates showed that results could be assessed without instrumentation;
      moreover, if the rapid assay format was used, rigorous asepsis was not necessary.
      Accuracy of the resazurin method was confirmed by plate counting from microwells
      and MIC values were compared with results obtained using an agar dilution assay.
      The MIC results obtained by the resazurin method were slightly lower than those
      obtained by agar dilution.

PMID- 9633652
TI  - Rapid identification of diverse Campylobacter lari strains isolated from mussels
      and oysters using a reverse hybridization line probe assay.
AB  - Campylobacters isolated from mussels and oysters in The Netherlands were analysed
      by a novel assay, based on DNA amplification with primers, based on semiconserved
      GTP-binding sites of a putative GTPase gene. Polymerase chain reaction (PCR) was
      followed by a single step reverse hybridization line probe assay (PCR-LiPA). This
      permits identification of Campylobacter jejuni, C. coli, C. lari and C.
      upsaliensis. Among a group of 44 isolates, three C. jejuni, one C. upsaliensis,
      one double infection with C. jejuni and C. coli, and 38 C. lari strains were
      identified. These results were in complete agreement with conventional
      identification methods and whole cell protein analysis. One C. hyointestinalis
      isolate was not identified by the PCR-LiPA, since the reverse hybridization assay
      does not comprise specific probes for this particular species. PCR products from
      36 C. lari isolates were sequenced and phylogenetic analysis revealed the
      presence of two major C. lari subgroups: one comprised 11 highly homologous
      sequences, whereas the 25 sequences in the other subgroup were more
      heterogeneous. This confirmed earlier findings that C. lari isolates comprise a
      more heterogeneous group of isolates as compared with C. jejuni, C. coli and C.
      upsaliensis. Based on the sequence information, a novel PCR-LiPA was developed
      that permits specific and rapid detection of the different C. lari variants.

PMID- 9633653
TI  - The survival and growth of acid-adapted mesophilic pathogens that contaminate
      meat after lactic acid decontamination.
AB  - Lactic acid decontamination (LAD) may adapt pathogens to lactic acid. Such
      organisms may have an increased resistance to acid and can contaminate meat after
      LAD. The survival and growth of acid adapted Campylobacter jejuni, Salmonella
      typhimurium. Escherichia coli O157:H7 and Staphylococcus aureus inoculated on
      skin surface of still warm pork belly cuts 2 h after LAD was examined during
      chilled (4 degrees C) storage and refrigeration abuse equivalent to 12.5 degrees
      C. Lactic acid decontamination included dipping in 1, 2 or 5% lactic acid
      solutions at 55 degrees C for 120 s. Lactic acid decontamination brought sharp
      reductions in meat surface pH, but these recovered with time after LAD at
      approximately 1-1.5 pH units below that of water-treated controls. A sharp
      decrease in the number of cfu of pathogens occurred on chilled 2-5% lactic acid
      treated pork belly cuts when the skin surface was less than pH 4.8-5.2. The
      reductions ranged from 0.1-0.3 log10 cfu cm-2 for E. coli O157:H7 to over 1.7-2.4
      log10 cfu cm-2 for Camp. jejuni, respectively. Increase in storage temperature
      from 4 to 12.5 degrees C reduced delayed decrease in numbers of all pathogens
      except Camp. jejuni by a factor of two. Deaths in Camp. jejuni at 12.5 degrees C
      slightly exceeded those at 4 degrees C. After the initial sharp decline, the
      number of cfu of mesophilic pathogens decreased gradually at a rate similar to
      that on water-treated controls. Growth of all mesophilic pathogens except Camp.
      jejuni on 2-5% LAD meat occurred during storage at 12.5 degrees C when the meat
      surface pH exceeded 4.8-5.2, and was slower than on water-treated controls. Low
      temperature and acid-adapted E. coli O157:H7, Salm. typhimurium and Staph.
      aureus, and acid adapted Camp. jejuni that contaminate skin surface after hot 2
      5% LAD, did not cause an increased health hazard, although microbiota and
      intrinsic parameters (lactic acid content, pH) were created that could advantage
      their survival and growth.

PMID- 9633654
TI  - Purification and characterization of thermophilin T, a novel bacteriocin produced
      by Streptococcus thermophilus ACA-DC 0040.
AB  - ACA-DC 0040 produced an antimicrobial agent, which was named thermophilin T,
      active against several lactic acid bacteria strains of different species and food
      spoilage bacteria, such as Clostridium sporogenes C22/10 and Cl. tyrobutyricum
      NCDO-1754. The crude antimicrobial compound is sensitive to proteolytic enzymes
      and alpha-amylase, heat-stable (100 degrees C for 30 min), resistant to pH
      exposure at pH 1-12 and demonstrates a bactericidal mode of action against the
      sensitive strain Lactococcus cremoris CNRZ-117. The production of bacteriocin was
      optimized approximately 10-fold in an aerobic fermenter held at constant pH 5.8
      and 6.2. Ultrafiltration experiments with culture supernatant fluids containing
      the bacteriocin, and further estimation of molecular weight with gel filtration
      chromatography, revealed that bacteriocin in the native form has a molecular
      weight in excess of 300 kDa. SDS-gel electrophoresis of partially purified
      thermophilin T showed that bacteriocin activity was associated with a protein
      band of approximately 2.5 kDa molecular mass.

PMID- 9633655
TI  - Improved detection of bacteria by flow cytometry using a combination of antibody
      and viability markers.
AB  - A proprietary fluorogenic marker for cell viability (Chemchrome) was investigated
      for the detection of bacteria using flow cytometry. This marker was used in
      combination with fluorescently labelled monoclonal antibodies (against Salmonella
      typhimurium). Owing to the former's broad band emission spectrum, it was
      necessary to use the novel dye RED613 for the antibodies. This combined protocol,
      being sensitive only to the live Salm. typhimurium cells, reduced errors due to
      intrinsic fluorescence and non-specific binding. Detection of the order of 100
      cells ml-1 was achieved in 30 min. This level was achieved even in the presence
      of large numbers of non-target or dead organisms.

PMID- 9633657
TI  - Characterization of natural isolate Lactobacillus acidophilus BGRA43 useful for
      acidophilus milk production.
AB  - Lactobacillus acidophilus BGRA43 was selected from a set of human origin isolates
      of Lact. acidophilus strains for the highest growth rates and antagonistic effect
      against both Gram-positive and Gram-negative bacteria. The strain BGRA43 also
      exhibited an inhibitory effect on the growth of Clostridium sporogenes.
      Inhibition of this strain seems to be due to lactic acid production rather than
      hydrogen peroxide or bacteriocin. Growth of Lact. acidophilus BGRA43 in non-fat
      skim milk for 6 h at 37 degrees C resulted in a lowering of the pH value to 4.53.
      Besides the fast acidification, this strain generated a high viscosity of skim
      milk. These characteristics make the strain BGRA43 attractive for acidophilus
      milk production. Lactobacillus acidophilus BGRA43 produces an extracellular
      proteinase. Whole cells efficiently degraded casein for 3 h at 37 degrees C
      especially alpha- and beta-casein fractions. Total DNA isolated from the strain
      BGRA43 did not show any hybridization with lactococcal proteinase probes
      indicating that this strain produces a distinctive proteinase.

PMID- 9633656
TI  - Development and use of a multiplex PCR system for the rapid screening of heat
      labile toxin I, heat stable toxin II and shiga-like toxin I and II genes of
      Escherichia coli in water.
AB  - Enterotoxigenic Escherichia coli (ETEC) may produce heat-labile toxin (LT) I and
      LTII and heat-stable toxin (ST) I and STII, while shiga toxin producing E. coli
      (STEC) strains, including enterohaemorrhagic E. coli (EHEC), may produce shiga
      like toxin (SLT) I and/or SLTII. Both ETEC and STEC are pathogenic to humans,
      pigs and cattle. As contamination of environmental water by any of these
      pathogenic E. coli cells is possible, a multiplex polymerase chain reaction (PCR)
      system for the rapid screening of LTI, STII, and SLTI and SLTII genes of E. coli
      was developed. The PCR primers used were the SLTI and SLTII genes specific
      primers developed by the present authors and the LTI and STII genes specific
      primers reported by other laboratories. The detection specificity of this
      multiplex PCR system was confirmed by PCR assay of ETEC, STEC and other E. coli
      cells as well as non-E. coli bacteria. Its detection limit was 10(2)-10(3) cfu
      each of the target cells per assay. When this multiplex PCR system was used for
      the rapid screening of LTI, STII ETEC and STEC in water samples such as tap,
      underground and lake waters, it was found that after the enrichment step, as few
      as 10(0) cells 100 ml-1 of the water sample could be detected. Therefore, this
      PCR system could be used for the rapid monitoring of ETEC and/or STEC cells
      contaminating water samples.

PMID- 9633658
TI  - Characterization of Lactobacillus sake isolates from dry-cured sausages by
      restriction fragment length polymorphism analysis of the 16S rRNA gene.
AB  - Lactobacillus sake strains originally isolated from dry-fermented sausages were
      characterized by phenotypic and genotypic methods, including DNA-DNA
      hybridization, restriction fragment length polymorphism (RFLP), and 16S rDNA
      sequencing analysis, in order to establish their taxonomic position and relation
      to well defined reference species. Initially, isolates of Lact. sake showing a
      characteristic phenotype (melibiose-positive, maltose- and arabinose-negative)
      were identified by DNA-DNA hybridization. Subsequently, RFLP studies using EcoRI
      and HindIII as restriction enzymes, and cDNA from Escherichia coli or 16S rDNA
      from Lact. sake strains as probes, showed distinct polymorphism levels. Thus,
      EcoRI-digested DNA probed with cDNA from E. coli disclosed the presence of a
      unique cluster for the meat isolates tested, allowing their differentiation from
      the reference type strain. When HindIII-digested DNA was hybridized with the cDNA
      probe, strain-specific patterns were obtained, showing a higher discrimination
      power. Considerable strain differentiation was also observed when EcoRI and
      HindIII digests were hybridized with 16S rDNA probes. Finally, sequence analysis
      of the 16S rDNA from one isolate also revealed a certain degree of genetic
      variability with respect to the reference strain of Lact. sake.

PMID- 9633659
TI  - Bacterial-fungal biofilms in flowing water photo-processing tanks.
AB  - A complex seven species model community, including bacteria and fungi, was
      selected from organisms isolated from the walls of an industrial flowing water
      system. Growth rates of the species were determined in single and mixed batch
      culture growth. The rates were found to be significantly higher in mixed culture
      for Pseudomonas alcaligenes and Flavobacterium indologenes and higher in single
      culture for Xanthomonas maltophilia, Rhodotorula glutinis and Fusarium solani,
      whereas no significant difference was recorded for Alcaligenes denitrificans and
      Fusarium oxysporum. All species attached to PVC in single and mixed culture to
      form biofilms. Xanthomonas maltophilia, Alc. denitrificans, Ps. alcaligenes and
      F. solani biofilm cell densities cm-2 were significantly higher than attachment
      of the component species in mixed culture. Statistical analyses showed a
      significant difference in rate of colonization between single and mixed cultures
      for some species. No significant difference was noted between mixed culture cell
      densities cm-2 at laminar flows of Reynolds number 2.7 and 5.4.

PMID- 9633660
TI  - Water quality in rural Australia.
AB  - Grab samples of drinking water collected from reservoirs and from creeks flowing
      over pristine land, farmland or land having mixed use were analysed for their
      physicochemical and microbiological characteristics. A significant difference
      between sites for conductivity and sites for pH was noted using a two-way ANOVA.
      No significant interactions were detected between any of the other parameters:
      Giardia, Cryptosporidium, Escherichia coli, coliforms, plate count, turbidity or
      rainfall.

PMID- 9633661
TI  - Sensitivity to commercial disinfectants, and the occurrence of plasmids within
      various Listeria monocytogenes genotypes isolated from poultry products and the
      poultry processing environment.
AB  - The European Suspension Test was used to assess the relative resistance of 19
      individual Listeria monocytogenes genotypes, isolated from the poultry processing
      environment, to three commercially used disinfectants employed in the plant at
      the time of their isolation. To establish the relative resistance between the
      strains, the concentration of each disinfectant was reduced until inter-strain
      variation became apparent. For Darasan 214 and 7058, variation was detected at
      0.1% and 0.5% v/v, respectively, while Daraclean 7361 had to be reduced to only
      2.5% v/v. At these concentrations, the mean microbiocidal effect (ME) of each
      disinfectant ranged between 4.3 and 3.1 log10 reduction in cfu ml-1. Significant
      differences between the strains were obtained with respect to their resistance to
      the disinfectants employed (P < 0.01), but the overall log10 reduction for
      genotypes 'A1' and 'A2', which were found to persist in the poultry processing
      environment, were not found to be significantly different from the genotypes
      which had been isolated on a more sporadic basis (P > 0.05). The L. monocytogenes
      strains fell into four groups with respect to incidence and size of plasmids
      isolated. The first group contained strains which carried two plasmids (5 and 40
      MDa) and the other three (groups 2, 3 and 4) comprised strains which carried a
      single plasmid (14, 47 and 52 MDa, respectively). There was no correlation
      between persistent and sporadic strains with respect to incidence and size of
      plasmids isolated. Moreover, the strains which carried no plasmids were found to
      be as resistant to the disinfectants as those which did carry plasmids,
      suggesting that the plasmids isolated did not confer resistance of L.
      monocytogenes planktonic cells to the disinfectants tested. Therefore, it is
      unlikely that the strains which had been found to persist in the poultry
      processing environment did so by means of plasmid-mediated resistance to the
      commercial disinfectants used.

PMID- 9633662
TI  - Evaluation of the extent and type of bacterial contamination at different stages
      of processing of cooked ham.
AB  - In an attempt to determine the composition and origin of the spoilage flora of
      refrigerated vacuum-packed cooked ham, the changes in microbial numbers and types
      were followed along the processing line. Results revealed Lactobacillus sake and
      Leuconostoc mesenteroides ssp. mesenteroides as the major causative agents of
      spoilage of sliced ham stored at 4 degrees C and 12 degrees C, due to
      recontamination in the cutting room. On the contrary, the progressive
      deterioration of whole ham under the same storage conditions was associated with
      a non-identifiable group of leuconostoc-like bacteria. Except for lactic acid
      bacteria, no other organism grew in vacuum packs of either sliced or whole ham.
      Although atypical leuconostocs could not be detected among isolates recovered
      from freshly produced whole ham, they appeared to survive cooking and proliferate
      during storage. Neither these organisms however, nor Lact. sake and Leuc.
      mesenteroides were important in curing and tumbling as carnobacteria, mainly
      Carnobacterium divergens, and Brochothrix thermosphacta dominated at this stage.
      A progressive inversion of the ham microflora from mostly Gram-negative at the
      beginning of processing to highly Gram-positive prior to cooking was noted.
      Listeria monocytogenes cross-contaminated ham during tumbling. However, the
      pathogen was always absent from the vacuum-packed product provided that heating
      to a core temperature of 70 degrees C occurred and recontamination during slicing
      and packing was prevented. The percentage distribution of different species of
      lactic acid bacteria as well as the uncommon phenotypic characteristics of some
      strains were discussed.

PMID- 9633663
TI  - Specific assays for bacteria using phage mediated release of adenylate kinase.
AB  - A sensitive and rapid assay method for the specific detection of bacteria was
      developed using Escherichia coli and Salmonella newport as the test organisms.
      Bacteriophages were used to provide specific lysis of the bacteria and then the
      release of cell contents was measured by ATP bioluminescence. Increased
      sensitivity was obtained by focusing on the bacteria's adenylate kinase (AK) as
      the cell marker instead of ATP as conventionally used. Fewer than 10(3) E. coli
      cells could be readily detected in less than 1 h. Salmonella newport assays,
      although as sensitive, were slower and took up to 2 h. The effects of the culture
      medium, the phage, and the presence of non-specific bacteria were examined.

PMID- 9633664
TI  - Airborne movement of anthrax spores from carcass sites in the Etosha National
      Park, Namibia.
AB  - Tests for airborne movement of anthrax spores downwind from three heavily
      contaminated carcass sites were carried out under a range of wind conditions.
      Anthrax spores were detected in just three of 43 cyclone or gelatin filter air
      samples taken at distances of 6, 12 and 18 m from the sites. In addition, nine
      positives resulted during sampling sessions in which the site was mechanically
      disturbed, with a further five positives being found in sessions subsequent to
      those in which the site had been disturbed. The three positive samples not
      related to man-made disturbance were associated with the highest winds
      experienced during the study. Despite colony counts exceeding 100 on the culture
      plates in three instances, calculations showed that these represented very low
      worst case probable spore inhalation rates for animals or humans exposed to such
      levels. The low number of positives, the clear pattern of rapidly declining
      numbers of anthrax spores with distance downwind from the centres of the sites
      apparent on settle plates, and the persisting levels of contamination despite
      wind and rain, collectively suggest that the anthrax spores were associated with
      fairly heavy particles, although this was not seen by electron microscopy on soil
      samples from the sites. Overall, the findings are interpreted as indicating that
      it is very unlikely that Etosha animals contract anthrax by the inhalation route
      while simply in transit near or across a carcass site. The significance of the
      observations in relation to weather conditions in the Etosha, other studies on
      particulate aerosols in the region, and reports of long-distance airborne
      movement of microbes, is discussed.

PMID- 9633665
TI  - Heat shock and thermotolerance of Escherichia coli O157:H7 in a model beef gravy
      system and ground beef.
AB  - Duplicate beef gravy or ground beef samples inoculated with a suspension of a
      four-strain cocktail of Escherichia coli O157:H7 were subjected to sublethal
      heating at 46 degrees C for 15-30 min, and then heated to a final internal
      temperature of 60 degrees C. Survivor curves were fitted using a linear model
      that incorporated a lag period (TL), and D-values and 'time to a 4D inactivation'
      (T4D) were calculated. Heat-shocking allowed the organism to survive longer than
      non-heat-shocked cells; the T4D values at 60 degrees C increased 1.56- and 1.50
      fold in beef gravy and ground beef, respectively. In ground beef stored at 4
      degrees C, thermotolerance was lost after storage for 14 h. However, heat-shocked
      cells appeared to maintain their thermotolerance for at least 24 h in ground beef
      held to 15 or 28 degrees C. A 25 min heat shock at 46 degrees C in beef gravy
      resulted in an increase in the levels of two proteins with apparent molecular
      masses of 60 and 69 kDa. These two proteins were shown to be immunologically
      related to GroEL and DnaK, respectively. Increased heat resistance due to heat
      shock must be considered while designing thermal processes to assure the
      microbiological safety of thermally processed foods.

PMID- 9633666
TI  - The structure of psychosis: latent class analysis of probands from the Roscommon
      Family Study.
AB  - BACKGROUND: The nosologic structure of psychotic illness, still influenced as
      much by historical as empirical perspectives, remains controversial. METHODS:
      Latent class analysis was applied to detailed symptomatic and outcome assessments
      of probands (n=343) with broadly defined schizophrenia and affective illness
      ascertained from a population-based psychiatric registry in Roscommon County,
      Ireland. First-degree relatives (n=942) were assessed by personal interview
      and/or review of hospital record. RESULTS: Six classes were found, all of which
      bore substantial resemblance to current or historical nosologic constructs. In
      order of decreasing frequency, they were (1) classic schizophrenia, (2) major
      depression, (3) schizophreniform disorder, (4) bipolar-schizomania, (5)
      schizodepression, and (6) hebephrenia. These classes differed on many historical
      and clinical variables not used in the latent class analysis. Compared with
      relatives of controls, significantly increased rates of major depression were
      seen in relatives of depressed and schizodepressed probands. Significantly
      increased rates of bipolar illness were restricted to relatives of bipolar
      schizomanic probands. The risks for schizophrenia and schizophrenia spectrum
      disorders were significantly increased in relatives of all proband classes except
      major depression. This increase was moderate for bipolar-schizomanic probands,
      substantial for schizophrenic, schizophreniform, and schizodepressed probands,
      and marked for hebephrenic probands. CONCLUSIONS: These results suggest a
      relatively complex typology of psychotic syndromes consistent neither with a
      unitary model nor with a Kraepelinian dichotomy. The familial vulnerability to
      psychosis extends across several syndromes, being most pronounced in those with
      schizophrenialike symptoms. The familial vulnerability to depressive and manic
      affective illness is somewhat more specific.

PMID- 9633667
TI  - From Kraepelin to Kretschmer leavened by Schneider: thextransition from
      categories of psychosis to dimensions of variation intrinsic to homo sapiens.

PMID- 9633668
TI  - The structure of psychosis: syndromes and dimensions.

PMID- 9633669
TI  - Sympathetic activity in patients with panic disorder at rest, under laboratory
      mental stress, and during panic attacks.
AB  - BACKGROUND: The sympathetic nervous system has long been believed to be involved
      in the pathogenesis of panic disorder, but studies to date, most using peripheral
      venous catecholamine measurements, have yielded conflicting and equivocal
      results. We tested sympathetic nervous function in patients with panic disorder
      by using more sensitive methods. METHODS: Sympathetic nervous and adrenal
      medullary function was measured by using direct nerve recording (clinical
      microneurography) and whole-body and cardiac catecholamine kinetics in 13
      patients with panic disorder as defined by the DSM-IV, and 14 healthy control
      subjects. Measurements were made at rest, during laboratory stress (forced mental
      arithmetic), and, for 4 patients, during panic attacks occurring spontaneously in
      the laboratory setting. RESULTS: Muscle sympathetic activity, arterial plasma
      concentration of norepinephrine, and the total and cardiac norepinephrine
      spillover rates to plasma were similar in patients and control subjects at rest,
      as was whole-body epinephrine secretion. Epinephrine spillover from the heart was
      elevated in patients with panic disorder (P=.01). Responses to laboratory mental
      stress were almost identical in patient and control groups. During panic attacks,
      there were marked increases in epinephrine secretion and large increases in the
      sympathetic activity in muscle in 2 patients but smaller changes in the total
      norepinephrine spillover to plasma. CONCLUSIONS: Whole-body and regional
      sympathetic nervous activity are not elevated at rest in patients with panic
      disorder. Epinephrine is released from the heart at rest in patients with panic
      disorder, possibly due to loading of cardiac neuronal stores by uptake from
      plasma during surges of epinephrine secretion in panic attacks. Contrary to
      popular belief, the sympathetic nervous system is not globally activated during
      panic attacks.

PMID- 9633670
TI  - Catecholamines and pathogenesis in panic disorder.

PMID- 9633671
TI  - Effects of tryptophan depletion vs catecholamine depletion in patients with
      seasonal affective disorder in remission with light therapy.
AB  - BACKGROUND: Although hypotheses about the therapeutic mechanism of action of
      light therapy have focused on serotonergic mechanisms, the potential role, if
      any, of catecholaminergic pathways has not been fully explored. METHODS: Sixteen
      patients with seasonal affective disorder who had responded to a standard regimen
      of daily 10000-lux light therapy were enrolled in a double-blind, placebo
      controlled, randomized crossover study. We compared the effects of tryptophan
      depletion with catecholamine depletion and sham depletion. Ingestion of a
      tryptophan-free amino acid beverage plus amino acid capsules was used to deplete
      tryptophan. Administration of the tyrosine hydroxylase inhibitor alpha-methyl
      paratyrosine was used to deplete catecholamines. Diphenhydramine hydrochloride
      was used as an active placebo during sham depletion. The effects of these
      interventions were evaluated with measures of depression, plasma tryptophan
      levels, and plasma catecholamine metabolites. RESULTS: Tryptophan depletion
      significantly decreased plasma total and free tryptophan levels. Catecholamine
      depletion significantly decreased plasma 3-methoxy-4-hydroxyphenylethyleneglycol
      and homovanillic acid levels. Both tryptophan depletion and catecholamine
      depletion, compared with sham depletion, induced a robust increase (P<.001,
      repeated-measures analysis of variance) in depressive symptoms as measured with
      the Hamilton Depression Rating Scale, Seasonal Affective Disorder Version.
      CONCLUSIONS: The beneficial effects of light therapy in the treatment of seasonal
      affective disorder are reversed by both tryptophan depletion and catecholamine
      depletion. These findings confirm previous work showing that serotonin plays an
      important role in the mechanism of action of light therapy and provide new
      evidence that brain catecholaminergic systems may also be involved.

PMID- 9633672
TI  - Rapid tryptophan depletion, sleep electroencephalogram, and mood in men with
      remitted depression on serotonin reuptake inhibitors.
AB  - BACKGROUND: In previous studies, depletion of brain serotonin by administration
      of a tryptophan-free amino acid drink (TFD) (1) temporarily reversed the
      antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) in
      euthymic patients who had a history of major depression, and (2) enhanced rapid
      eye movement (REM) sleep in normal volunteers. In this study, we hypothesized
      that the TFD would not only increase depressive symptoms but also the propensity
      for REM sleep in euthymic patients treated with SSRIs. METHODS: Ten fully
      remitted, medicated male patients who had a history of major depressive episode
      ingested a 100-g TFD (the experimental dose) or a 25-g TFD (designed to be the
      control drink) in double-blind, random order on separate days. The effects were
      assessed with mood ratings, plasma tryptophan concentrations, and an all-night
      sleep electroencephalogram. RESULTS: The TFDs produced a dose-dependent reduction
      in plasma tryptophan concentrations, sleep latency, and REM latency, as well as
      increased REM percentage, REM minutes, REM density, and total sleep time. Neither
      strength of TFD altered mood to a clinically significant degree. CONCLUSIONS:
      Although the TFD affected plasma tryptophan concentrations and various sleep
      measures, our study did not confirm previous reports that TFD temporarily
      reversed the antidepressant effects of SSRIs in euthymic patients. Our patients,
      however, had been treated for a longer period with SSRIs and were more fully
      remitted at the time of the study. Our results suggest that TFD-induced relapse
      in SSRI-treated patients in remission decreases as a function of treatment
      duration, degree of remission, or both.

PMID- 9633673
TI  - Cerebral gray matter volume deficits in first episode psychosis.
AB  - BACKGROUND: Structural brain differences including decreased gray matter and
      increased cerebrospinal fluid volumes have been observed in the brains of
      chronically ill patients with schizophrenia. We hypothesized that deficits in
      gray matter volume would be present in patients presenting with a first episode
      of nonaffective psychosis. METHODS: We used magnetic resonance imaging to compare
      the brains of 77 patients assessed as having a first episode of psychosis
      (meeting DSM-III-R criteria for schizophrenia, schizophreniform disorder,
      schizoaffective disorder, delusional disorder, or psychotic disorder not
      otherwise specified) with those of 61 healthy controls matched for age, sex,
      race, and parental socioeconomic status. Axial, dual-echo scans of the whole
      brain were segmented into gray matter, white matter, and cerebrospinal fluid
      compartments using a computerized volumetric approach. These measures were
      corrected for the significant effects of intracranial volume and age prior to
      performing between-group comparisons. RESULTS: The first episode psychosis group
      had significantly smaller gray matter volume (t[136] = -2.2; P = .03) and greater
      cerebrospinal fluid volume (t[136] = 2.5; P = .02) than normal controls. In the
      patient group, gray matter volumes were positively correlated with estimates of
      IQ but not with age of onset, duration of illness, or measures of premorbid
      functioning. CONCLUSIONS: Deficits in gray matter volume are present in patients
      experiencing first episode nonaffective psychosis. The magnitude of these
      differences is smaller than has been described in more chronically ill patients.

PMID- 9633674
TI  - Expressed emotion and psychiatric relapse: a meta-analysis.
AB  - BACKGROUND: Expressed emotion (EE) is a measure of the family environment that
      has been demonstrated to be a reliable psychosocial predictor of relapse in
      schizophrenia. However, in recent years some prominent nonreplications of the EE
      relapse relationship have been published. To more fully address the question of
      the predictive validity of EE, we conducted a meta-analysis of all available EE
      and outcome studies in schizophrenia. We also examined the predictive validity of
      the EE construct for mood disorders and eating disorders. METHODS: An extensive
      literature search revealed 27 studies of the EE-outcome relationship in
      schizophrenia. Using meta-analytic procedures, we combined the findings of these
      investigations to provide an estimate of the effect size associated with the EE
      relapse relationship. We also used meta-analysis to provide estimates of the
      effect sizes associated with EE for mood and eating disorders. RESULTS: The
      results confirmed that EE is a significant and robust predictor of relapse in
      schizophrenia. Additional analyses demonstrated that the EE-relapse relationship
      was strongest for patients with more chronic schizophrenic illness.
      Interestingly, although the EE construct is most closely associated with research
      in schizophrenia, the mean effect sizes for EE for both mood disorders and eating
      disorders were significantly higher than the mean effect size for schizophrenia.
      CONCLUSION: These findings highlight the importance of EE in the understanding
      and prevention of relapse in a broad range of psychopathological conditions.

PMID- 9633675
TI  - A prospective study of heart rate response following trauma and the subsequent
      development of posttraumatic stress disorder.
AB  - BACKGROUND: Physiological arousal during traumatic events may trigger the
      neurobiological processes that lead to posttraumatic stress disorder (PTSD). This
      study prospectively examined the relationship between heart rate and blood
      pressure recorded immediately following a traumatic event and the subsequent
      development of PTSD. METHODS: Eighty-six trauma survivors who presented at the
      emergency department of a general hospital were followed up for 4 months. Heart
      rate and blood pressure were recorded on arrival at the emergency department.
      Heart rate, anxiety, depression, and PTSD symptoms were assessed 1 week, 1 month,
      and 4 months later. The clinician-administered PTSD scale defined PTSD status at
      4 months. RESULTS: twenty subjects (23%) met PTSD diagnostic criteria at the 4
      month assessment (PTSD group), and 66 (77%) did not (non-PTSD group). Subjects
      who developed PTSD had higher heart rates at the emergency department (95.5+/
      13.9 vs 83.3+/-10.9 beats per minute, t=4.4, P<.001) and 1 week later (77.8+/
      11.9 vs 72.0+/-9.5 beats per minute, t=2.25, P<.03), but not after 1 and 4
      months. The groups did not differ in initial blood pressure measurement. Repeated
      measures analysis of variance (ANOVA) for heart rate showed a significant group
      effect (P<.02), time effect (P<.001), and group x time interaction (P<.001). The
      time effect and group x time interaction remained significant when adjusted for
      sex, age, trauma severity, immediate response, and dissociation during the
      traumatic event. CONCLUSION: Elevated heart rate shortly after trauma is
      associated with the later development of PTSD.

PMID- 9633676
TI  - Psychotherapy and managed care.

PMID- 9633677
TI  - The role of psychotherapy: psychiatry's resistance to managed care.

PMID- 9633678
TI  - Current and emerging drug therapies in the management of Parkinson's disease.

PMID- 9633679
TI  - History of levodopa and dopamine agonists in Parkinson's disease treatment.
AB  - Striatal dopamine deficiency in Parkinson's disease (PD), first described in
      1960, was a key event that led to the era of levodopa therapy. In 1961, levodopa
      was first tried in PD patients, but throughout most of the 1960s the results were
      inconsistent. In 1967, questions about the effectiveness of levodopa in PD were
      finally set aside when Cotzias and colleagues reported dramatic improvement in PD
      patients with oral administration of levodopa in increasing amounts over long
      periods. The major side effects of levodopa administration, i.e., dyskinesias and
      motor fluctuations, also became apparent at this time. In the early 1970s, the
      advantages of adding a dopa decarboxylase inhibitor to treatment were discovered-
      reducing side effects and gaining better symptom control--and the first levodopa
      combination, carbidopa/levodopa, became commercially available in 1975. Since
      then, PD researchers have attempted to overcome complications with such
      techniques as continuous levodopa infusion and, most recently, long-acting
      levodopa combinations. A dopamine agonist, apomorphine, was used in 1970 as a
      means to overcome side effects and loss of levodopa efficacy. However, side
      effects and difficulty of administration limited its use. Dopamine agonists began
      to find a place in routine treatment of PD after the discovery of bromocriptine's
      benefits in PD in 1974. Since then, new approaches have been tried, such as
      dopamine agonist monotherapy and early therapy in combination with levodopa. The
      development of new dopamine agonists has led to characterization of dopamine
      receptor subtypes and agonists targeted to stimulation of specific receptors.

PMID- 9633680
TI  - Mechanism of action of dopaminergic agents in Parkinson's disease.
AB  - As the substantia nigra degenerates in Parkinson's disease (PD), the
      nigrostriatal pathway is disrupted, reducing striatal dopamine and producing PD
      symptoms. Although dopamine does not readily cross the blood-brain barrier, its
      precursor, levodopa, does. Levodopa is absorbed in the small bowel and is rapidly
      catabolized by aromatic-L-amino-acid decarboxylase (AADC) and catechol-O
      methyltransferase (COMT). Because gastric AADC and COMT degrade levodopa, the
      drug is given with inhibitors of AADC (carbidopa or benserazide), and inhibitors
      of COMT will also enter clinical use. Although the exact site of decarboxylation
      of exogenous levodopa to dopamine in the brain is unknown, most striatal AADC is
      located in nigrostriatal dopaminergic nerve terminals. Newly synthesized dopamine
      is stored in the terminals and then released, stimulating postsynaptic dopamine
      receptors and mediating the antiparkinsonian action of levodopa. Dopamine
      agonists act directly on postsynaptic dopamine receptors, thus obviating the need
      for metabolic conversion, storage, and release. How the actions of dopaminergic
      drugs produce side effects and how these side effects should be managed are
      discussed.

PMID- 9633681
TI  - Implications of the 5-year CR FIRST trial. Sinemet CR Five-Year International
      Response Fluctuation Study.
AB  - Almost since the introduction of levodopa for Parkinson's disease (PD), its side
      effects have concerned clinicians. One strategy to avoid side effects has been to
      delay levodopa therapy; an alternative has been to use early therapy but to avoid
      fluctuations in plasma levodopa levels. This latter strategy led to the
      development of sustained-release carbidopa-levodopa, which was compared with
      immediate-release carbidopa-levodopa in the CR Five-Year International Response
      Fluctuation Study (FIRST), a 5-year multicenter study of early, levodopa-naive PD
      patients. The incidence of motor fluctuations was lower than expected for both
      groups, and patients receiving sustained-release carbidopa-levodopa fared better
      on the activities of daily living portion of the Unified Parkinson's Disease
      Rating Scale and on portions of the Nottingham Health Profile. The trial
      demonstrated the value of low-dose therapy, the lack of toxicity of this low-dose
      approach over 5 years in early PD.

PMID- 9633682
TI  - Initiating therapy for Parkinson's disease.
AB  - Accurate diagnosis and individualized assessment of the risks and benefits of
      available antiparkinsonian medications should guide initiation of treatment for
      patients with early Parkinson's disease (PD). In general, the goals of treatment
      for younger patients (less than age 60 years) are control of impairing symptoms,
      sparing of levodopa to minimize long-term complications, and consideration of
      neuroprotection. The primary initial medication choices for patients under age 50
      years include selegiline, amantadine, and anticholinergic agents. Patients in
      their fifties may require a dopamine agonist in addition to or instead of
      selegiline to achieve adequate symptom control. If the desired response is still
      not achieved, sustained-release carbidopa-levodopa should be added, followed by
      adjunctive amantadine or anticholinergic therapy. For older patients (60 years
      and over), improvement of functional impairment is the primary goal. For these
      patients, a special concern is to avoid inducing or exacerbating cognitive
      impairment. Sustained-release carbidopa-levodopa is considered first-line
      treatment for these patients. Inadequate response can be handled by a trial of
      immediate-release carbidopa-levodopa and then addition of a dopamine agonist when
      maximum levodopa doses are reached. Anticholinergic agents, amantadine, and
      selegiline should be avoided because of their CNS effects.

PMID- 9633683
TI  - Adjuncts to levodopa therapy: dopamine agonists.
AB  - The classical role of dopamine agonists in Parkinson's disease (PD) therapy is
      adjunctive treatment to levodopa once "wearing-off" fluctuations or more
      malignant types of "on-off" swings have developed. Dopamine agonists reduce the
      frequency, severity, and duration of "off" periods while allowing the levodopa
      dose to be reduced. Interest is growing in the role of dopamine agonists as
      primary monotherapy in PD. Studies of early monotherapy have shown that, even
      with sustained treatment, drug-induced dyskinesias rarely develop. However, this
      approach is successful for more than 3 years in only about 30% of all PD
      patients. Continuous dopaminergic stimulation via subcutaneous dopamine agonist
      infusions is being investigated as a way to control levodopa-associated peak-dose
      dyskinesias. Early combined treatment with levodopa has been suggested as
      effective while avoiding long-term complications, but the therapy remains
      controversial. Despite the entry of several new dopamine agonists into clinical
      practice, the ideal agonist, with long duration of action and efficacy equal to
      that of levodopa, is still lacking. The clinical pharmacology of dopamine
      agonists is reviewed.

PMID- 9633684
TI  - Extending levodopa action: COMT inhibition.
AB  - Degradation of levodopa in the periphery is known to be associated with motor
      fluctuations and dyskinesia in Parkinson's disease (PD) patients. The enzyme
      catechol-O-methyltransferase (COMT) is responsible for much of this degradation.
      Therefore, inhibiting COMT activity is one method of extending the action of
      levodopa. The new nitrocatechol-type COMT inhibitors entacapone, nitecapone, and
      tolcapone inhibit COMT in the periphery; tolcapone also inhibits COMT activity
      centrally. COMT inhibitors increase patients' duration of response to levodopa
      and reduce response fluctuations. Administration may prolong levodopa-induced
      dyskinesia, but peak-dose dyskinesia does not appear to increase. To reduce
      dyskinesia, the total daily dose of levodopa can be reduced.

PMID- 9633685
TI  - Managing the neuropsychiatric symptoms of Parkinson's disease.
AB  - Neuropsychiatric symptoms frequently complicate the treatment of Parkinson's
      disease (PD). Approximately 27% of PD patients are demented, and approximately
      19% are cognitively impaired without being demented. These 46% of patients are
      prone to development of delirium when they take antiparkinsonian drugs.
      Approximately 40% of PD patients are depressed. The depression may be endogenous
      or exogenous, apathetic or agitated. Approximately 40% of PD patients are anxious
      or have panic attacks. The attacks may or may not be associated with depression.
      This article reviews the diagnosis of these symptoms and discusses their
      management.

PMID- 9633686
TI  - Levodopa neurotoxicity: experimental studies versus clinical relevance.
AB  - Levodopa therapy remains the major form of treatment for the symptoms of
      Parkinson's disease (PD). However, there has been a suspicion that its use may
      hasten the progression of nigral cell degeneration. This concept is based on the
      ability of levodopa to generate reactive oxygen species and the apparent
      involvement of oxidative stress as a component of the degenerative process that
      occurs in PD. Indeed, in vitro autoxidation of levodopa causes oxidative stress,
      leading to neuronal destruction by necrosis or apoptosis. However, its chronic
      administration to normal rats or primates has not been associated with clear
      evidence for destruction of the nigrostriatal pathway. In contrast, in situations
      in which the nigrostriatal tract is already damaged, there is some evidence to
      suggest that levodopa treatment can produce further cell destruction associated
      with oxidative processes. However, levodopa does not appear to be toxic to the
      development of fetal nigral neurons or to the survival of fetal cell transplants.
      There is no clinical evidence to suggest that levodopa has adverse effects on
      dopamine cells in normal humans or on the viability of remaining dopaminergic
      cells in patients with PD. However, it is only now that specific clinical trials
      designed to examine the potential neurotoxicity of levodopa are being undertaken.

PMID- 9633687
TI  - Intravenous diphenylhydantoin in treatment of acute repetitive seizures. 1968.

PMID- 9633688
TI  - Genotypes, phenotypes, and frontotemporal dementia: take your pick.

PMID- 9633689
TI  - The use and cost of medical resources: what will we pay for neurologic health?

PMID- 9633690
TI  - Tourette's syndrome and 'PANDAS': will the relation bear out? Pediatric
      autoimmune neuropsychiatric disorders associated with streptococcal infection.
AB  - Despite strong evidence of the importance of hereditary factors in the etiology
      of Tourette's syndrome (TS), research findings have consistently pointed to a
      role of environmental influences. A recent line of research has suggested that
      tic disorders and associated behavioral disturbances, such as obsessive
      compulsive disorder, might develop following streptococcal infection by the
      process of molecular mimicry, whereby antibodies directed against bacterial
      antigens cross-react with brain targets. Such investigations have given rise to
      the notion that there is a spectrum of childhood neurobehavioral disorders
      (termed pediatric autoimmune neuropsychiatric disorders associated with
      streptococcal infection [PANDAS]) that arise by postinfectious autoimmune
      mechanisms. This article reviews research results supporting the concept of
      PANDAS and discusses their limitations. Well-designed and adequately controlled
      studies are needed to determine whether there is a true etiologic relation
      between streptococcal infection and the onset or exacerbation of childhood
      neuropsychiatric disorders and whether the use of immune-modifying therapies for
      these conditions is rational.

PMID- 9633691
TI  - The behavioral neurology of cerebral white matter.
AB  - Behavioral neurology has primarily focused on brain-behavior relations as
      revealed by disorders of the cerebral cortex and subcortical gray matter.
      Disorders of cerebral white matter have received less attention. This article
      considers the contribution of cerebral white matter to normal behavioral function
      and the effects of white matter disorders on behavior. Diffuse dysfunction is
      more common than focal impairment, and the term white matter dementia has been
      proposed as a clinical entity. Conventional neuroimaging has enabled more
      accurate identification of white matter regions participating in neurobehavioral
      operations, and newer imaging techniques may define white matter connectivity
      within and between the hemispheres. As an essential component of neural networks,
      cerebral white matter contributes to cognitive and emotional functions, and
      lesions of white matter disconnect these networks to produce neurobehavioral
      syndromes.

PMID- 9633692
TI  - Familial aggregation in frontotemporal dementia.
AB  - OBJECTIVE AND BACKGROUND: Frontotemporal dementia (FTD) is a common, non
      Alzheimer's dementia. Its familial occurrence has been reported, but the
      frequency of positive family history is unknown. METHODS: We carried out a
      nationwide genetic-epidemiologic study of FTD in the Dutch population of 15
      million people. The family history of dementia was analyzed in 74 FTD patients
      and 561 age- and gender-matched control subjects. RESULTS: We found one or more
      first-degree relatives with dementia before age 80 in 38% (28 of 74) of FTD
      patients, but only in 15% (84 of 561) of control subjects. Ten percent of FTD
      patients had two or more first-degree relatives with dementia compared with 0.9%
      of the control subjects. Seven percent of FTD patients showed the ApoE4E4
      genotype versus 2.3% of the control subjects. The first-degree relatives of FTD
      had a risk of 22% for dementia before age 80 compared with 11% in relatives of
      control subjects. The age of onset of dementia in affected first-degree relatives
      of FTD patients (60.9+/-10.6 years) was significantly lower than among affected
      relatives of control subjects (72.3+/-8.5 years). The first-degree relatives of
      FTD patients were 3.5 times (95% CI, 2.4 to 5.2) more at risk for developing
      dementia before age 80 than relatives of control subjects. The hazard ratio in
      the subgroup with unknown linkage to chromosome 17 was 2.4 (95% CI, 1.5 to 3.7).
      CONCLUSION: This study documents the importance of genetic factors in a
      proportion of FTD patients with the age at onset of dementia in first-degree
      relatives being 11 years earlier than in the general population.

PMID- 9633693
TI  - Hereditary dysphasic disinhibition dementia: a frontotemporal dementia linked to
      17q21-22.
AB  - OBJECTIVE: The clinical and pathologic features of hereditary dysphasic
      disinhibition dementia (HDDD) are described to determine whether it is a variant
      of known dementias. BACKGROUND: Several dementing disorders have clinical and
      pathologic similarities with AD, Pick's disease, and the "nonspecific" dementias.
      A detailed description of clinical and pathologic presentation will aid
      classification, but ultimately the discovery of causative gene(s) will define
      these disorders. METHODS: The authors performed a clinical assessment: gross and
      microscopic pathologic evaluation of brain tissue, genetic linkage studies, and
      sequence analyses. RESULTS: HDDD is an autosomal-dominant frontotemporal dementia
      with many similarities to Pick's disease. Salient clinical features are global
      dementia with disproportionate dysphasia and "frontotemporal" symptoms. A linkage
      between HDDD and 17q21-22 was shown, with a maximum lod score of 3.68 at zero
      recombination. CONCLUSIONS: Several dementias have been linked to the same region
      and have been termed frontotemporal dementia with parkinsonism linked to
      chromosome 17. These disorders may represent phenotypic variants arising from
      mutations within a common gene.

PMID- 9633694
TI  - Association of CYP2D microsatellite polymorphism with Lewy body variant of
      Alzheimer's disease.
AB  - OBJECTIVE: To examine the genetic association of CYP2D6 locus with Lewy body
      variant (LBV) and Parkinson's disease (PD). METHODS: Allelic association was
      studied in patients with pure AD, LBV, and PD by using the CYP2D microsatellite,
      the (dG-dT)n dinucleotide repeat (n=16 to 27) located between CYP2D8P and CYP2D7
      genes, and the CYP2D6 B and D mutations. RESULTS: We found overrepresentation of
      the alleles longer than 21 repeat (the long-type alleles) in LBV (allele
      frequency, 0.313) (odds ratio=1.99, p=0.019 by chi2 test) and in PD (0.298) (odds
      ratio=1.86, p=0.037), but not in pure AD (0.196), compared with the age-matched
      control (0.186). Strong association was noted of the long-type alleles with the
      CYP2D6 B mutation (odds ratio=88.50, p < 0.001 by Fisher's exact test), but not
      with the D mutation or the deletion of CYP2D6 gene. CONCLUSIONS: The CYP2D locus
      is closely associated with LBV and PD. The CYP2D6 B mutation may be involved in
      pathogenesis of LBV and PD in a dominant-negative manner, or in the linkage
      disequilibrium of the CYP2D microsatellite to another pathogenic gene locus.

PMID- 9633695
TI  - Preclinical prediction of Alzheimer's disease using SPECT.
AB  - BACKGROUND: Regional cerebral perfusion measured by single photon emission
      computed tomography (SPECT) was examined as a preclinical predictor of the
      development of Alzheimer's disease (AD). METHODS: Singular value decomposition
      was used to produce 20 SPECT factors (known as vectors) (n=152). Vector scores
      were then computed for four groups (n=136), differing in cognitive status: Group
      1--normal controls at both baseline and follow-up; Group 2--subjects with
      "questionable" AD at both baseline and follow-up; Group 3--subjects with
      questionable AD at baseline who converted to AD on follow-up (Converters); Group
      4--subjects with AD at baseline. All SPECT data in the analyses were gathered at
      baseline. RESULTS: The four groups could be distinguished on the basis of their
      baseline SPECT data (p < or = 0.00005; hit rate=83%). Regional decreases in
      perfusion were most prominent among Converters in the hippocampal-amygdaloid
      complex, the posterior cingulate, the anterior thalamus, and the anterior
      cingulate. Inclusion of apolipoprotein E status did not significantly improve the
      discrimination. CONCLUSIONS: SPECT data gathered and analyzed in this manner may
      be useful as one aspect of the preclinical prediction of AD. Three of the four
      brain regions important for discriminating Converters from normal controls
      involve a distributed brain network pertaining to memory, suggesting that this
      network may be selectively affected in the earliest stages of AD.

PMID- 9633696
TI  - Incidence and subtypes of dementia in southern Taiwan: impact of socio
      demographic factors.
AB  - OBJECTIVE: To determine the incidence rate (IR) and subtypes of dementia in
      southern Taiwan. METHODS: From a cohort of 2,915 community inhabitants aged 65
      years and over, 2,507 and 2,175 subjects participated in the first- and second
      year follow-up surveys, respectively. A two-phase study used the Mini-Mental
      State Examination in phase I and the Consortium to Establish a Registry of
      Alzheimer's Disease (CERAD) neuropsychological battery and the neurobehavioral
      examination in phase II. We applied International Classification of Diseases
      (ICD)-10NA criteria for dementia, National Institute of Neurological and
      Communication Disorders and Stroke-Alzheimer's Disease and Related Disorders
      Association (NINCDS-ADRDA) guidelines for Alzheimer's disease (AD), and National
      Institute of Neurological Disorders and Stroke-Association Internationale pour la
      Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria for vascular
      dementia (VaD). RESULTS: The annual IR for total dementia was 1.28%, which
      increased with age from 0.77% for 65- to 74-year-olds to 6.19% for persons aged
      85 years or older. AD (25 cases, 41.7%, IR=0.54%) was the most common cause of
      dementia, followed by VaD (19 cases, 31.7%, IR=0.41%) and mixed dementia (9
      cases, 15.0%). After adjusting for sex, increasing age was significantly
      associated with total dementia and AD (p < 0.01). Illiteracy was associated with
      a marginally increased risk for total dementia (aRR=1.59, p < 0.1) as was being
      female for AD (aRR = 1.92, p < 0.1). The 2-year mortality rate was high among the
      demented (48% in total dementia, 38% in AD, and 60% in VaD). CONCLUSIONS: The age
      specific incidence of dementia in Taiwan is approaching that of developed
      countries and the low prevalence of dementia (especially VaD) may be mainly due
      to the high mortality. Age was the major risk factor for total dementia and AD.
      Being female was probably a risk factor for AD, as was illiteracy for total
      dementia.

PMID- 9633697
TI  - Midlife cardiovascular risk factors, ApoE, and cognitive decline in elderly male
      twins.
AB  - OBJECTIVE: To investigate the combined effect of the apolipoprotein E epsilon4
      (ApoE*4) allele and midlife cardiovascular risk factors on cognitive decline.
      METHODS: Data are from the National Heart, Lung, and Blood Institute Twin Study-a
      longitudinal cardiovascular epidemiologic study of World War II male veteran
      twins currently in its 27th year of follow-up. Subjects were assessed for
      cardiovascular risk factors, including BP and glucose levels, at mean ages 48,
      58, and 63 years. Participants in the current study are 410 individual twin
      subjects for whom cognitive function was measured twice, at ages 63 and 73 years.
      Ten-year change scores in performance on neuropsychological test examinations
      were adjusted for age, education, baseline score, and incident cardiovascular
      disease. RESULTS: For the sample as a whole, we observed a significant decline (p
      < 0.01) in cognitive performance over the 10 years of follow-up. ApoE*4 carriers
      with midlife hyperglycemia experienced the greatest decline in performance, which
      was also greater than expected from the separate effects combined. Midlife
      hypertension and ApoE*4, were each associated with excess decline in performance
      on tests of psychomotor speed. Their joint effect, however, was not greater than
      expected from the separate effects combined. CONCLUSIONS: ApoE*4 and midlife
      cardiovascular risk factors may have a synergistic effect on decline in cognitive
      function. This effect may be due to greater vascular or degenerative damage among
      subjects with ApoE*4.

PMID- 9633698
TI  - Regional glucose metabolic abnormalities are not the result of atrophy in
      Alzheimer's disease.
AB  - OBJECTIVE: To determine whether the hypometabolism observed in PET images of
      patients with Alzheimer's disease (AD) is due entirely to brain atrophy.
      BACKGROUND: Reduced brain glucose metabolism in AD patients measured using PET
      has been reported by numerous authors. Actual glucose metabolic values in AD may
      be reduced artificially because of brain atrophy, which accentuates the partial
      volume effect (PVE) on data collected by PET. METHODS: Using segmented MR images,
      we corrected regional cerebral metabolic rates for glucose for PVEs to evaluate
      the effect of atrophy on uncorrected values for brain metabolism in AD patients
      and healthy control subjects. RESULTS: Global glucose metabolism was reduced
      significantly before and after correction in AD patients compared with controls.
      Before PVE correction, glucose metabolic values in patients were lower than in
      control subjects in the inferior parietal, frontal, and lateral temporal cortex;
      in the posterior cingulate; and in the precuneus. These reductions remained
      significantly lower after PVE correction, although in the posterior cingulate the
      difference in metabolism between AD patients and control subjects lessened.
      Regional glucose metabolism of these areas with PVE correction was lower in
      moderately-severely demented patients than in mildly demented patients.
      CONCLUSION: Reduced glucose metabolism measured by PET in AD is not simply an
      artifact due to an increase in CSF space induced by atrophy, but reflects a true
      metabolic reduction per gram of tissue.

PMID- 9633699
TI  - Health care utilization in multiple sclerosis: a population-based study in
      Olmsted County, MN.
AB  - OBJECTIVE: The authors sought to determine acute ambulatory- and hospital-billed
      charges for the Olmsted County, Minnesota Multiple Sclerosis (MS) Disability
      Prevalence Cohort and compare them to those incurred by the general population.
      METHODS: Billed charges for 155 people with clinically definite or laboratory
      supported MS were compared with those of age- and gender-matched non-MS controls.
      Billing data, including all inpatient and outpatient acute and rehabilitative
      medical care charges over a 5-year period surrounding a December 1, 1991
      prevalence date, were analyzed. Data were correlated with level of disability
      using the Minimal Record of Disability for MS. RESULTS: Median total annual
      billed charges for most individuals with MS, including those with less severe
      ($1,277) and relapsing-remitting illness ($1,348), did not differ from those for
      controls ($1,327, p=0.075). Only those with severe MS (22.6%) had median annual
      medical charges higher than controls ($5,440, p < 0.001). Male patients with MS
      had higher median annual total charges ($2,353) than male controls ($762,
      p=0.003). Total charges for female patients with MS ($1,440) were not different
      from those for female controls ($1469). Median annual outpatient charges were 15%
      more for the MS group ($1,418) than for controls ($1,231). Patients with MS had a
      mean of 0.2 hospital admissions annually compared with 0.1 annual admissions per
      control patient. Among variables collected on persons with MS, the Expanded
      Disability Status Scale was the strongest predictor of level of charges (p <
      0.001). CONCLUSION: Acute ambulatory- and hospital-billed charges for most
      patients with MS do not differ from those of the general population.

PMID- 9633700
TI  - Relation between MR abnormalities and patterns of cognitive impairment in
      multiple sclerosis.
AB  - OBJECTIVE: This study correlated the extent of abnormalities detected by
      different magnetic resonance imaging (MRI) techniques [proton density (PD)
      weighted, T1-weighted, and magnetization transfer imaging (MTI)] with the overall
      cognitive, frontal lobe, and memory impairments in patients with MS. PATIENTS:
      There were 30 clinically definite MS patients, with different disease courses.
      EXCLUSION CRITERIA: psychoactive/steroid treatments, mood disorders, acute
      relapse phase. MAIN OUTCOME MEASURES: Neuropsychological test results. Total
      (TLL) and frontal (FLL) lesion loads assessed from PD-weighted, T1-weighted (22
      patients), and MTI (22 patients) MRI scans. Average lesion MT ratios (MTR) and
      analysis of the MTR histograms from brain tissue axial slabs on MTI scans.
      RESULTS: Patients with frontal lobe deficits (n=15) or memory impairment (n-17)
      had a higher TLL on PD scans (p=0.04 and p=0.01, respectively). Patients with
      frontal lobe deficits had higher FLL on PD scans (p=0.01) and TLL on MTI (p=0.03)
      scans. No significant relationships between the extent of T1-weighted lesion
      loads and the presence of any neuropsychological impairment. Mean MTR of both MS
      lesions and whole brain tissue was lower in patients with frontal lobe impairment
      (p=0.04). MRI lesion loads correlated significantly with some neuropsychological
      test scores. CONCLUSIONS: Lesion loads on PD-weighted MRI and MTI-derived
      measures are associated with cognitive decline in MS patients. Overall
      macroscopic and microscopic brain damage is more important than the corresponding
      regional brain disease in determining deficits of selective cognitive domains.

PMID- 9633701
TI  - Correlation of volumetric magnetization transfer imaging with clinical data in
      MS.
AB  - We examined the relations between quantitative volumetric estimates of cerebral
      lesion load based on magnetization transfer imaging (MTI), clinical data, and
      measures of neuropsychological function in 44 patients with clinically diagnosed
      MS. In this population we assessed the correlation between several volumetric MTI
      measures, measures of neurologic function (Kurtzke Expanded Disability Status
      Scale and Ambulation Index), and disease duration using Spearman's correlation
      coefficient. Patients were classified on the basis of neuropsychological test
      performance as severely impaired, moderately impaired, and normal. We assessed
      differences between these groups with respect to MTI results using the Kruskal
      Wallis test. MTI measures corrected for brain volume were found to correlate with
      disease duration (p < 0.01) and showed suggestive correlations with measures of
      neurologic impairment (p < 0.05). Individual neuropsychological tests correlated
      with MTI measures corrected and not corrected for brain volume (p < 0.001). An
      MTI measure not corrected for brain volume differed (p < 0.05) between severely
      impaired, moderately impaired, and normal patients. These preliminary results
      suggest that volumetric MTI analysis provides new measures that reflect more
      accurately the global lesion load in the brain of MS patients, and they may serve
      as a method to study the natural course of the disease and as an outcome measure
      to evaluate the effect of drugs.

PMID- 9633702
TI  - Antibodies against human putamen in children with Tourette syndrome.
AB  - BACKGROUND: Similar to the model for Sydenham's chorea, antineuronal antibodies,
      which develop in response to a preceding streptococcal infection, have been
      speculated to have a role in the development of Tourette syndrome (TS). METHODS:
      Serum antibodies against human caudate, putamen, and globus pallidus (interna and
      externa) were assayed by enzyme-linked immunosorbent assay (ELISA) and Western
      blot techniques and results were correlated with clinical characteristics and
      markers of streptococcal infection. SUBJECTS: A total of 41 children with TS
      (mean age, 11.3 years) and 39 controls (mean age, 12.1 years) were included.
      RESULTS: Compared with controls, TS subjects had a significant increase in the
      mean (p=0.006) and median (p=0.002) ELISA optical density (OD) levels of serum
      antibodies against putamen, but not caudate or globus pallidus. Western blots on
      20 control and 20 TS serum samples showed that specific antibodies to
      caudate/putamen occurred more frequently in TS subjects at 83, 67, and 60 kDa;
      antigens were present in a synaptosomal fraction. TS subjects with a positive
      family history of tics had higher OD values (p < or = 0.04), but no association
      was shown with age of tic onset, tic severity, sudden onset of tics, or presence
      of attention-deficit hyperactivity disorder or obsessive-compulsive disorder.
      Risk ratio calculations in TS and control groups and in study subjects
      dichotomized for high and low putamen OD values were similar for titers of
      antistreptolysin O > or = 166 or antideoxyribonuclease B > or = 170. A subgroup
      analysis limited to subjects with elevated streptococcal titers, however, showed
      a significantly (p < or = 0.004) larger number of TS subjects with elevated OD
      levels. CONCLUSION: Children and adolescents with TS had significantly higher
      serum levels of antineuronal antibodies against putamen than did controls, but
      their relation to clinical characteristics and markers for streptococcal
      infection remains equivocal.

PMID- 9633703
TI  - Mouse bioassay versus Western blot assay for botulinum toxin antibodies:
      correlation with clinical response.
AB  - OBJECTIVE: To compare the mouse protection bioassay (MPB) to the Western blot
      assay (WBA) in detecting antibodies against botulinum toxin A (BTX-A) and to
      correlate the assay results with clinical responses to BTX-A injections. METHODS:
      MPB and WBA assay results were compared in 51 patients (34 nonresponders and 17
      responders) who received BTX-A injections, most commonly for cervical dystonia. A
      subset of patients received a "test" injection into either the right eyebrow (14)
      or right frontalis (12). RESULTS: Twelve patients with antibodies against BTX-A
      (Ab+) detected by WBA did not demonstrate antibodies (Ab-) by MPB. Conversely,
      five patients were Ab+ by MPB but Ab- by WBA. Specificity of the MPB was 100% on
      all three parameters (clinical, eyebrow, and frontalis injections), whereas WBA
      specificity was only 71% for clinical response but 100% for both eyebrow and
      frontalis responses. Sensitivities for both assays were low (33 to 53%). Of the
      16 patients previously Ab+ by MPB, seven became negative on retesting after a
      mean interval of 33 months (range, 6 to 93 months). CONCLUSIONS: The lower
      specificity of the WBA compared to the MPB suggests that the WBA detects
      nonblocking antibodies. Eyebrow and frontalis "test" injections correlated well
      with MPB and WBA results and with clinical responses and may be useful in the
      evaluation of BTX nonresponders.

PMID- 9633704
TI  - Parkinson's disease: improved function with GM1 ganglioside treatment in a
      randomized placebo-controlled study.
AB  - BACKGROUND/OBJECTIVE: Studies in animal models of Parkinson's disease (PD)
      suggest that GM1 ganglioside treatment can restore neurologic and dopaminergic
      function. In view of positive preclinical findings and the results of a previous
      open-label study demonstrating efficacy of GM1 in PD patients, this study
      compared effects of GM1 ganglioside and placebo on motor functions in PD
      patients. METHODS: Forty-five patients with mild to moderate PD were studied. The
      primary efficacy measure was change in the Unified Parkinson's Disease Rating
      Scale (UPDRS) motor score. After three independent baseline assessments, patients
      received IV infusion of the test drug (1,000 mg GM1 or placebo) and then self
      administered either GM1 or placebo twice daily (200 mg/day, subcutaneously) for
      16 weeks. Patients were examined during monthly follow-up visits. RESULTS: There
      was a significant difference between groups in UPDRS motor scores at 16 weeks
      (p=0.0001). The activities of daily living portion of the UPDRS (off-period
      assessment) also showed a significant effect in favor of the GM1-treated patients
      (p=0.04). GM1-treated patients also had significantly greater mean improvements
      than placebo-treated patients in performance of timed motor tests including tests
      of arm, hand, and foot movements, and walking. GM1 was well tolerated and no
      serious adverse events were reported. CONCLUSIONS: This study demonstrates that
      GM1 ganglioside treatment enhances neurologic function significantly in PD
      patients. Further study is warranted to evaluate long-term effects of GM1 in PD
      patients and to elucidate further the mechanisms underlying patient improvements.

PMID- 9633705
TI  - Progressive supranuclear palsy: a survey of the disease course.
AB  - BACKGROUND: The most accurate knowledge about progressive supranuclear palsy
      (PSP) comes from small sample studies that preclude precise estimation of the
      proportion of PSP patients affected with various symptoms and the examination of
      factors predicting survival time. OBJECTIVE: To describe the course of PSP in a
      large clinically diagnosed sample of PSP patients and to identify factors
      predicting survival time. METHODS: We surveyed the caregivers of 318 living and
      119 deceased patients with progressive supranuclear palsy. The main outcome
      measures were a principal symptom severity questionnaire and a signs and symptoms
      questionnaire. RESULTS: The estimated age of PSP symptom onset depends critically
      on how symptom onset is defined, with estimates differing by as much as 1.5
      years. Men and women were represented equally (51.6% versus 48.4%) in the living
      sample, but men formed 61.8% of the deceased sample. Men were diagnosed later
      than women following symptom onset (33.4 versus 24.1 months) and died earlier
      following the diagnosis (37.0 versus 47.6 months). Motor and visual symptoms
      appeared first, followed by emotional and personality problems, cognitive
      impairment, and sleep changes. Whereas motor symptoms eventually affected almost
      every patient, emotional/personality and cognitive symptoms did not. The early
      onset, presence of falls, slowness, and inability to move eyes downward early in
      the development of the disease predicted survival time. CONCLUSION: PSP is a
      rapidly progressive disease dominated by motor symptoms, and it affects men more
      frequently than women.

PMID- 9633706
TI  - Visuomotor control abnormalities in patients with unilateral parkinsonism.
AB  - Visuomotor performance is known to be disturbed in patients who have advanced
      Parkinson's disease (PD). The degree of impairment in the early stages of PD was
      investigated in both the symptomatic and asymptomatic hand of patients with
      unilateral disease. We examined the visuomotor performance of 10 early unilateral
      parkinsonian patients and 15 control subjects by using several tracing and
      tracking tasks that were performed with unseen hands, in which feedback was given
      through a screen cursor. Significant impairment in control of movement direction
      was found in tracing of screen paths but not in tracking. Significant slowing of
      movement was found in target tracking, whereas tracing velocity was normal.
      Although all patients were judged by standard clinical criteria to be
      unilaterally affected, visuomotor functions were found to be impaired equally in
      both hands. Visuomotor control of movement direction and movement velocity is
      performed independently. Performance along both control dimensions is impaired in
      the mild stages of parkinsonism, even before the appearance of motor symptoms.

PMID- 9633707
TI  - Effects of voluntary contraction on tibial nerve somatosensory evoked potentials:
      gating of specific cortical responses.
AB  - We evaluated vertex-parietal P37, N50, and contralateral N37 somatosensory evoked
      potentials (SEPs) to posterior tibial nerve stimulation during weak (20 to 30%)
      and strong (80 to 90%) ipsilateral gastrocnemius-soleus contraction. The results
      were compared with data obtained during full relaxation. P37 and N50 were
      attenuated significantly during weak contraction and then abolished during strong
      contraction, whereas the contralateral N37 was not. The N37 potential spreads
      over the vertex and over the ipsilateral parietal region during strong
      contraction. The Cz'-F3 montage was not appropriate for detecting these SEP
      patterns. These findings suggest that thalamic or cortical gating mechanisms
      affect specific cortical responses. P37 and N50 could reflect the arrival of the
      afferent volley into the motor areas from thalamic and cortical (subareas 1 and 2
      of S1) projections. N37 could be generated in subarea 3b. Differential analysis
      of N37 and P37 is required in clinical practice, mainly in those conditions that
      involve the motor system and in those conditions in which tonic muscular activity
      is increased.

PMID- 9633708
TI  - Practice styles of US compared to UK neurologists.
AB  - OBJECTIVE: This study assessed variation between neurologists in the United
      States and United Kingdom in their diagnostic and treatment decisions for
      commonly encountered neurologic presentations, and identified explanatory factors
      for any observed variation. METHODS: All 210 consultant neurologists in the
      United Kingdom and a nationally representative sample of 595 US neurologists
      received mailed surveys containing three detailed clinical scenarios depicting
      patients with (1) a single unprovoked seizure occurring 3 days previously, (2)
      early Parkinson's disease, and (3) dementia. The main study outcome measures were
      self-reported decisions regarding diagnostic test ordering and treatment, which
      were assessed after each scenario. Neurologists' practice characteristics,
      certainty about the diagnosis, and attitudes toward uncertainty were also
      measured. Survey response rates were 92% of US and 63% of UK neurologists.
      RESULTS: A higher proportion of US than UK neurologists indicated they would
      order additional diagnostic tests for all three scenarios (all p < 0.05); 77% of
      UK compared with 26% of US neurologists would manage a single unprovoked seizure
      without antiepileptic medication (p < 0.0001), but treatment of early Parkinson's
      disease was not different. Nearly all US and UK neurologists would obtain a
      neuroimaging study in the evaluation of dementia. International differences
      persisted after adjustment for differences in demographic and practice
      characteristics and for attitudes toward test use and clinical uncertainty.
      CONCLUSIONS: We identified large international variation in clinical decisions
      across three common neurologic conditions. Cross-country collaboration should
      explore these differences to develop consensus on standards of care.

PMID- 9633709
TI  - Ischemic stroke: outcomes, patient mix, and practice variation for neurologists
      and generalists in a community.
AB  - A variety of methods was used to compare patient mix, practice variation,
      survival, and recurrence after first ischemic stroke among Rochester, MN
      residents. The significance of the results for neurologists and generalists was
      examined. Age, stroke severity, congestive heart failure (CHF), and the
      interaction between atrial fibrillation and patient groups were determinants of
      survival. Without atrial fibrillation, patients on neurology services and
      patients on general services with neurology consultation had better survival than
      those without neurology consultation, adjusting for age, stroke severity, and
      CHF. With atrial fibrillation, patients on general services with neurology
      consultation had no better survival compared with those without neurology
      consultation; patients on neurology services had worse survival (p=0.002). There
      was no difference in stroke recurrence. Evaluation by a neurologist is associated
      with better survival for most patients with ischemic stroke but not those with
      atrial fibrillation. Only a randomized trial can determine whether this
      association is causal.

PMID- 9633710
TI  - Cognitive screening examinations for silent cerebral infarcts in sickle cell
      disease.
AB  - OBJECTIVE: In children with sickle cell disease (SCD), silent cerebral infarcts
      are the most frequent cause of neurologic injury. We determined the sensitivity
      and specificity of selective neurocognitive measures when separating children
      with silent cerebral infarcts and SCD from sibling controls. Additionally, we
      tested the validity of the same cognitive measures to identify patients with
      overt strokes. METHODS: We examined performance on a neuropsychologic battery
      containing measures of attention/executive, spatial, language, memory, and motor
      functioning for seven children with SCD and silent cerebral infarct, 21 children
      with SCD and overt stroke, and 17 normal siblings. Diagnosis of cerebral infarct
      was based on results of MRI. RESULTS: Measures from the attention and executive
      domains were the most useful for identifying children with silent cerebral
      infarct. The Test of Variables of Attention was the most robust measure and
      yielded a sensitivity rate of 86% and a specificity rate of 81%. This measure
      also showed a sensitivity rate of 95% in identifying overt stroke. CONCLUSIONS:
      Brief cognitive screening measures, if properly constructed, may be an effective
      means of identifying children with silent cerebral infarct. Future prospective
      studies should be pursued to assess the utility of cognitive screening for silent
      cerebral infarcts in SCD.

PMID- 9633711
TI  - Pneumatic sequential compression reduces the risk of deep vein thrombosis in
      stroke patients.
AB  - OBJECTIVE: To determine if pneumatic sequential compression devices (SCDs)
      combined with subcutaneous heparin and antiembolic hose reduce the risk of deep
      vein thrombosis (DVT) and pulmonary embolism (PE) in stroke patients. BACKGROUND:
      DVTs and PEs are serious complications among hospitalized stroke patients.
      Subcutaneous heparin and SCDs have both been used to prevent DVT. It is not known
      if SCDs combined with subcutaneous heparin can improve the protection afforded by
      heparin alone. METHODS: The study group was comprised of nonhemorrhagic stroke
      patients admitted to the neurology service from October 1988 through June 1996.
      From October 1988 through April 1991 (233 patients), and during February 1993 (16
      patients), patients received 5,000 U subcutaneous heparin twice daily and
      antiembolic hose. From June 1991 through January 1993 and from March 1993 through
      June 1996 (432 patients) all nonambulatory stroke patients had SCDs applied to
      both legs in addition to subcutaneous heparin and antiembolic hose. RESULTS:
      Twenty-three of 249 patients (9.2%; 21 of 233 and two of 16 patients) treated
      with heparin alone developed DVT and six patients (2.4%) developed PE (six of 233
      and zero of 16). Half the PE cases (three of six) were fatal and all PEs were in
      patients with DVT. Eighty-three of the 249 patients were nonambulatory. Twenty
      two of the 23 DVTs and all the PEs developed in nonambulatory patients. Only one
      DVT (0.23%) and no PEs occurred among the 432 patients (148 nonambulatory)
      treated with SCDs as well as heparin. The addition of SCDs resulted in more than
      a 40-fold reduction in the risk of DVT. CONCLUSIONS: Nonambulatory stroke
      patients have an increased risk for DVT and PE. Adding SCDs to treatment with
      subcutaneous heparin and antiembolic hose reduced the risks of DVTs and PEs. SCDs
      should be considered for adjunctive DVT prophylaxis in nonambulatory stroke
      patients.

PMID- 9633712
TI  - Illicit drug-associated ischemic stroke in the Baltimore-Washington Young Stroke
      Study.
AB  - BACKGROUND: Limited information exists on the frequency, trends in occurrence,
      risk factors, mechanisms, and outcome of ischemic stroke associated with illicit
      drug use among young adults in a geographically defined population. METHODS: We
      reviewed ischemic stroke in young adults (aged 15 to 44 years) in 46 regional
      hospitals for 1988 and 1991. We examined stroke mechanisms and outcome in
      patients with recent drug use. RESULTS: Recent illicit drug use was noted in
      51/422 (12.1%) stroke patients. Patients with drug use were more likely than
      other stroke patients to be black (p=0.01), aged 25 to 39 years (p=0.004), and
      smokers (p=0.006), and were less likely to have hypertension (p=0.004) or
      diabetes mellitus (p=0.004). Drug use was the probable cause of stroke in 20
      (4.7%) patients. Among 31 (7.3%) patients with drug use as a possible stroke
      mechanism, more likely diagnoses included cardioembolic stroke in 18,
      hematologic/collagen vascular in 6, nonatherosclerotic vasculopathy in 5, and
      atherosclerosis in 3. There was no difference in outcome between drug-associated
      and non-drug associated stroke. CONCLUSIONS: Recent illicit drug use occurs in
      12.1% of young adult stroke patients. Drug-associated young adult stroke seems to
      relate to vascular mechanisms other than those related to hypertension or
      diabetes. Case-control studies are needed.

PMID- 9633713
TI  - Dolichoectasia of the intracranial arteries in patients with first ischemic
      stroke: a population-based study.
AB  - OBJECTIVE: The objective of this study was to estimate the frequency of
      intracranial arterial dolichoectasia among patients with first ischemic stroke
      and to compare clinical characteristics, survival, and recurrence in those with
      and without the abnormality. BACKGROUND: Dolichoectasia may cause cerebral
      infarction by thrombosis, embolism, stenosis, or occlusion of deep penetrating
      arteries. METHODS: The chi-square, Fisher's exact, and logrank tests were used to
      compare clinical characteristics, survival, and recurrence for patients with and
      without dolichoectasia among the 387 residents of Rochester, MN, who had brain CT
      or MRI for first cerebral infarction from 1985 through 1989. RESULTS: Twelve
      patients (3.1%) had dolichoectasia. Patients with dolichoectasia were more likely
      to have had stroke fitting a clinical and radiographic pattern of lacunar
      infarction than those without (42% and 17% respectively; p=0.04). Dolichoectasia
      was detected in the vertebrobasilar system in eight patients (66.7%), in the
      carotid system in two patients (16.7%), and in both circulatory systems in two
      patients (16.7%). There were no significant differences in the following
      characteristics among those with and without dolichoectasia: age, sex,
      hypertension, diabetes, smoking, and preceding transient ischemic attack.
      Patients with dolichoectasia had better survival (relative risk [RR] for death,
      0.26; p=0.04) after first cerebral infarction but higher rates of stroke
      recurrence (RR, 2.4; p=0.02). CONCLUSIONS: Dolichoectasia is detected in 38 of
      patients with first cerebral infarction and is associated with better survival
      but higher rates of stroke recurrence.

PMID- 9633714
TI  - Arterial territories of the human brain: cerebral hemispheres.
AB  - The development of neuroimaging has allowed clinicians to improve clinicoanatomic
      correlations in patients with stroke. Anatomic structures are well delineated on
      MRI, but there is a lack of standardization in their arterial supply. As in our
      previous study depicting the arterial supply of the brainstem and cerebellum, we
      present a system of 12 axial sections of the hemispheres depicting the dominant
      arterial territories, the most important anatomic structures, and Brodmann's
      areas. The area of variation of the cortical territory of the anterior, middle,
      and posterior cerebral arteries is also represented. These sections may be used
      as a practical tool to determine arterial territories on CT or MRI, and may help
      establish consistent clinicoanatomic correlations in patients with supratentorial
      stroke.

PMID- 9633715
TI  - A longitudinal study of patients with venous malformations: documentation of a
      negligible hemorrhage risk and benign natural history.
AB  - BACKGROUND: The natural history of cerebral venous malformations has not been
      well documented, and the clinical significance of these common lesions remains
      controversial. OBJECTIVE: The objective of this study was to follow
      longitudinally the clinical course of patients with cerebral venous malformations
      to document the natural history of the lesion. METHODS: Ninety-two patients with
      radiographically confirmed venous malformations were entered into the study
      between 1987 and 1996. Annual follow-up was maintained by clinic visits and/or
      phone interviews. Sixty-three patients (25 men and 38 women) with more than 1
      year of follow-up were analyzed. McNemar's test and logistic regression analysis
      was applied to prevalence of presenting symptoms over time. An average per
      patient follow-up of 4.2 years yielded 2,721 retrospective and 301 prospective
      lesion-years for analysis. RESULTS: Average age at diagnosis was 39.1 years (SD,
      18.7 years; range, 2 to 73 years). The most frequent lesion locations included
      the frontal lobe (55.6%, n=35) and the cerebellum (27%, n=17). The most frequent
      presentations included headache (50.8%, n=32), focal neurologic deficits (39.7%,
      n=25), and seizure (30.2%, n=19). Prevalence of headache (p=0.048) and seizure
      (p=0.016) decreased over time without treatment of the lesion. A second
      cerebrovascular lesion was identified in 12 patients (19%). Two patients had a
      symptomatic intracerebral hemorrhage attributable to their venous malformation.
      Risk of hemorrhage was 0.15% per lesion-year (95% CI, 0.06 to 0.38%).
      CONCLUSIONS: This study establishes that the natural history of venous
      malformations is benign, that the risk of hemorrhage from these lesions is
      negligible, and that conservative therapy is warranted.

PMID- 9633716
TI  - SPECT study of a German CADASIL family: a phenotype with migraine and progressive
      dementia only.
AB  - OBJECTIVE: We describe the clinical, molecular, genetic, MRI, and SPECT features
      of a German family with autosomal dominant migraine and dementia, mapping to the
      cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) locus. We studied the correlation of cerebral blood
      flow, MRI, and cognitive function. BACKGROUND: CADASIL is a small-vessel disease
      of the brain mapped to chromosome 19p13.1. Mutations of the Notch3 gene cause
      this disorder. Most phenotypes are characterized by transient ischemic attacks
      (TIAs) and lacunar strokes leading to dementia. Migraine is frequent. A single
      photon emission computed tomographic (SPECT) study of this disorder has not yet
      been published. METHODS: We studied 13 individuals clinically and performed
      neuroimaging studies with MRI and SPECT. RESULTS: Genetic analysis strongly
      supported linkage to the CADASIL locus, and the disease haplotype was found in
      six individuals. Analysis by single-strand confirmation polymorphism did not
      identify Notch3 mutations. All affected individuals had MRI white matter
      hyperintensities and four individuals had additional basal ganglial signal
      abnormalities. Four affected individuals had migraine, two of whom had slowly
      progressive dementia. TIAs, stroke, and focal neurologic signs were absent.
      Cerebral blood flow reduction in SPECT studies of affected individuals matched
      with MRI signal abnormalities. Cognitive impairment was linked to signal
      abnormalities and hypoperfusion in the basal ganglia. Demented patients had a
      pattern of frontal, temporal, and basal ganglial hypoperfusion. CONCLUSIONS: We
      describe a CADASIL phenotype that is characterized by the absence of focal
      neurologic symptoms and present the first SPECT study of this disorder.

PMID- 9633717
TI  - Persistent inflammatory response in stroke survivors.
AB  - OBJECTIVE: Goals were to determine how long acute-phase markers remain elevated
      after ischemic stroke and how marker levels relate to stroke risk factors, stroke
      mechanism, and subsequent vascular events. METHODS: Fibrinogen (FIB), C-reactive
      protein (CRP), leukocytes (WBC), neutrophils (PMN), interleukin-6, and
      interleukin-1 receptor antagonist were measured at stroke onset and at 6 weeks, 6
      months, and 1 year after enrollment, or until a vascular event occurred in 136
      acute ischemic stroke patients, 76 patients with comparable risk factors for
      stroke, and 48 age-balanced healthy subjects. RESULTS: Multivariate logistic
      analysis showed that prior stroke and FIB level predicted new events in stroke
      patients (p < 0.04 for both), whereas congestive heart failure (p < 0.02) and
      creatinine level (p < 0.006) were predictive in at-risk patients. After
      controlling for infection, FIB, CRP, and PMN levels at baseline were higher in at
      risk but not in stroke patients with recurrent events (p < 0.05 for all). At 1
      year, FIB levels remained elevated in event-free stroke survivors compared with
      levels in the risk and control groups (p < 0.001 for both). FIB also remained
      higher in stroke survivors who had atheroembolism (AE) compared with non-AE
      stroke survivors (381+/-72 versus 342+/-78 mg/dL, p < 0.02). Peripheral vascular
      disease was an independent predictor (p < 0.0001) of longitudinal FIB in stroke
      survivors. Of note, both WBC and PMN levels were chronically elevated in patients
      with stroke risk factors and in stroke survivors (p < 0.0001 for both) compared
      with healthy elderly subjects. CONCLUSIONS: Most acute-phase markers decline
      gradually after stroke, but FIB remains significantly elevated and is associated
      with increased risk for recurrent vascular events.

PMID- 9633718
TI  - Childhood headache at school entry: a controlled clinical study.
AB  - OBJECTIVE: Our objective was to study the prevalence of different headache types,
      characterizations, and triggers of headache in Finnish children starting school.
      METHODS: Questionnaires were sent to 1,132 families with 6-year-old children.
      Children with headache disturbing their daily activities (n=96) and an
      asymptomatic control group of children (n=96) participated in a clinical
      interview and examination. RESULTS: Children with headache had significantly more
      bruxism (odds ratio [OR], 1.9; 95% CI, 1.0 to 3.4), tenderness in the occipital
      muscle insertion areas (OR, 4.8; 95% CI, 1.8 to 12.7), and tenderness in the
      temporomandibular joint areas (OR, 2.8; 95% CI, 1.3 to 6.0). They also had more
      travel sickness (OR, 3.4; 95% CI, 1.7 to 6.7) than control children. Eating ice
      cream (OR, 5.3; 95% CI, 1.4 to 20.3), fear (OR, 3.7; 95% CI, 1.2 to 11.2), and
      anxiety (OR, 3.2; 95% CI, 1.0 to 10.8) triggered headache more often in
      migraineurs than in children with tension-type headache. Children with migraine
      also reported more frequently abdominal (OR, 5.6; 95% CI, 1.7 to 18.1) and other
      (OR, 3.5; 95% CI, 1.2 to 9.8) pain concurrently with headache, and they used
      medication for pain relief more often (OR, 3.1; 95% CI, 1.0 to 9.5). CONCLUSIONS:
      Headache classification in children may be improved by palpation of occipital
      muscle insertions and temporomandibular joint areas, and by discerning a history
      of triggering events and concurrent symptoms.

PMID- 9633719
TI  - Global cerebral blood flow, blood volume, and oxygen metabolism in patients with
      migraine headache.
AB  - OBJECTIVE: Migraine headaches with and without aura are representative of
      vascular headache states traditionally thought to be mediated by alterations in
      vascular tone. Validation of this theory has been hampered in part by technical
      difficulties inherent in the measurement of cerebral blood flow (CBF). The
      purpose of this study was to compare CBF measured during migraine and migraine
      free states using PET. METHODS: Patients with a minimum of one migraine headache
      without aura per month (International Headache Society [IHS] criteria) underwent
      measurement of CBF, cerebral blood volume (CBV), oxygen extraction, and
      metabolism during an episode of spontaneous migraine headache. Imaging was
      repeated during a migraine-free period of at least 48 hours. PET radiotracers
      used were: CBF, H(2)15O; CBV, C15O; oxygen metabolism, 15O2. RESULTS: In nine
      patients (seven female and two male), global CBF (mL/min/100 g [SD]) was measured
      as 52.70 (6.9) during migraine and 59.65 (10.6) in the migraine-free state;
      p=0.028. CBV (mL/100 g [SD]) was 3.6 (0.43) during the symptomatic state and 3.8
      (0.55) after the migraine; p=0.047. Oxygen metabolism (mL/min/100 g [SD]) was
      3.68 (0.9) during migraine and 3.38 (1.02) without headache; p=0.211. The oxygen
      extraction ratio was 0.48 (0.15) and 0.41 (0.12) during migraine and migraine
      free states, respectively; p=0.132. CONCLUSIONS: In patients experiencing
      migraine without aura, CBF and CBV are reduced during the headache phase.
      Cerebral oxygen metabolism and oxygen extraction are not significantly affected.

PMID- 9633720
TI  - Migraine and reduced work performance: a population-based diary study.
AB  - OBJECTIVE: This article estimates lost work days and lost work day equivalents in
      a population sample of migraineurs, differentiating work loss due to headache
      episodes that met criteria for migraine from migrainous headaches not meeting
      full criteria and nonmigrainous headaches. METHODS: A random digit dialing survey
      of 5,071 adults identified 800 subjects with migraine headaches. By clinical
      examination, a subsample of 225 met migraine diagnostic criteria; 174 of these
      patients completed at least 11 weeks of daily diaries. This report concerns the
      subgroup of 122 individuals with regular paid employment. Subjects completed a
      daily diary over a 3-month period to assess the occurrence of headaches and
      International Headache Society (IHS) criteria for each headache occurrence. We
      report estimates of lost work days and lost work day equivalents by type of
      headache. RESULTS: Participants reported headaches on 8.1 work days, of which 2.2
      headache days met criteria for migraine (IHS 1.1, 1.2), and an additional 2.1
      headache days were migrainous without meeting full migraine criteria (IHS 1.7).
      On average, migraineurs missed 1.1 days of work due to headache in 3 months, of
      which 0.7 lost work days were due to migraine and 0.3 were due to migrainous
      headaches. When at work with headache, work effectiveness was reduced 41% for
      migraine headaches, 28% for migrainous headaches, and 24% for other headaches.
      Over 3 months, migraineurs experienced an average of 3.0 lost work day
      equivalents, of which 1.4 were due to migraine and an additional 0.7 were due to
      migrainous headaches. The most disabled 20% of the participants accounted for 77%
      of the lost work days; 40% of subjects accounted for 75% of the lost work day
      equivalents. CONCLUSIONS: Employed migraine sufferers experienced considerable
      work loss and reduced work performance due to headache. The most severely
      affected migraineurs accounted for most of the reduced work performance.
      Targeting the most severely affected persons may be necessary to reduce work loss
      among migraineurs substantially.

PMID- 9633721
TI  - Quantitative analysis of cerebral vasculopathy in patients with Fabry disease.
AB  - OBJECTIVE: This study's purpose was to obtain a quantitative natural history of
      the cerebrovascular involvement in Fabry disease. BACKGROUND: Fabry disease is an
      X-linked recessive disorder due to alpha-galactosidase A deficiency. Progressive
      accumulation of ceramidetrihexoside within the intima and media of cerebral blood
      vessels causes ischemic lesions in the majority of affected patients.
      Determination of the natural history of the cerebral vasculopathy in Fabry
      disease is important to assess the effects of therapeutic intervention in this
      disorder. METHODS: A longitudinal MRI study of 50 patients who had a total of 129
      MRI scans was performed. The burden of cerebrovascular disease was determined
      using direct linear measurement. RESULTS: On T2-weighted MRI scans, 32% of the
      patients had no lesions (mean age, 33 years), 16% had gray matter lesions only
      (mean age, 36 years), 26% had lesions in white matter only (mean age, 43 years),
      and 26% had lesions in white and gray matter (mean age, 47 years). Disease burden
      increased with age, but no patient younger than 26 had lesions on MRI. All
      patients older than 54 had cerebrovascular involvement. The distribution of MRI
      detectable lesions was typical of a small-vessel disease. Only 37.5% of patients
      with cerebral lesions had neurologic symptoms. CONCLUSION: These findings provide
      a predictable outcome measure to assess the effect of molecular interventions on
      the cerebrovascular circulation in Fabry disease.

PMID- 9633722
TI  - Duplication of the proteolipid protein gene is the major cause of Pelizaeus
      Merzbacher disease.
AB  - BACKGROUND/OBJECTIVE: Pelizaeus-Merzbacher disease (PMD), an X-linked recessive
      dysmyelination disorder, is caused by mutations in the proteolipid protein (PLP)
      gene. However, missense mutations were only found in a fraction of PMD patients,
      even in families that showed linkage with the PLP locus on Xq22. Here we describe
      the use of an extended protocol that includes screening for both missense
      mutations and duplications. METHOD: Two groups of patients were analyzed, one
      group with 10 independent PMD families and one group with 24 sporadic patients
      suspected of PMD. Missense mutations in the PLP gene were identified by
      sequencing. PLP gene duplications were detected by quantitative polymerase chain
      reaction and/or Southern blot analysis. RESULTS: Sequencing of the PLP gene
      revealed four mutations in group 1 and one mutation in group 2. However,
      inclusion of duplication analysis in the screening protocol raised the amount of
      mutations found in group 1 from 40 to 90%, and in group 2 from 4 to 25%.
      CONCLUSIONS: These results demonstrate that duplications of the PLP gene are the
      major cause of PMD. Furthermore, it appears that the phenotype resulting from PLP
      duplications is relatively mild, and that many probands are nontypical PMD
      patients.

PMID- 9633723
TI  - CT imaging in adults with neurofibromatosis-1: frequent asymptomatic plexiform
      lesions.
AB  - OBJECTIVE: The authors examined the incidence and radiologic characteristics of
      plexiform neurofibromas in neurofibromatosis-1 (NF-1) to define a cohort at
      greatest risk for malignant nerve-sheath tumors. BACKGROUND: Plexiform
      neurofibromas are a frequent complication of NF-1. They can impair function,
      produce disfigurement, and be the site for the development of malignant nerve
      sheath tumors. The incidence and natural history of plexiform neurofibromas is
      unknown. METHODS: CT imaging of the chest, abdomen, and pelvis was performed in
      91 of 125 consecutive adults (age, > or = 16 years) with NF-1. RESULTS: Twenty
      percent of patients had plexiform neurofibromas of the chest in the paraspinal,
      mediastinal, or supraclavicular area. Approximately 40% of patients had abnormal
      abdominal/pelvic scans. The paraspinal, sacral plexus, sciatic notch, and
      perirectal regions were the most common sites. Most plexiform neurofibromas were
      asymptomatic. Imaging also revealed a number of tumors, including malignant nerve
      sheath tumors, adrenal tumors, carcinoids, and schwannomas. CONCLUSIONS: The
      frequency of plexiform lesions and other tumors in NF-1 indicates that clinicians
      should monitor young adults carefully; however, imaging characteristics alone
      cannot reliably distinguish benign from malignant lesions.

PMID- 9633724
TI  - Tethered cord syndrome in occult spinal dysraphism: timing and outcome of
      surgical release.
AB  - OBJECTIVE: To investigate the influence of neurosurgical intervention on the
      appearance of upper motor neuron (UMN) signs in newborns diagnosed with occult
      spinal dysraphism and tethered cord (TC) during the first month of life. METHODS:
      A prospective study (1990 to 1996) of 22 consecutive newborns with occult spinal
      dysraphism monitored for the appearance of UMN signs. Untethering was performed
      when neurologic or urodynamic investigation indicated the presence of UMN
      dysfunction. RESULTS: Of 22 patients, 10 remained free of UMN symptoms during
      follow-up (mean, 67+/-22 months). Untethering was performed in 12 of 22 patients
      because of the presence of UMN symptoms. In 7 of these 12 patients, there was a
      documented asymptomatic period of 13+/-11 months before the onset of UMN
      symptoms. Untethering at a mean age of 18+/-17 months restored normal neurologic
      and urinary function in all patients (mean postoperative follow-up, 25+/-16
      months). Of the 12 children, 5 presented with UMN signs at birth. In these
      children, untethering was performed at a mean age of 9+/-5 months. In two of
      these five patients, UMN symptoms did not resolve after surgery, and ongoing
      conservative bladder treatment was required (mean follow-up, 37+/-14 months). In
      none of the 12 operated children did signs of retethering occur. CONCLUSIONS: A
      significant number (10/22) of children born with occult spinal dysraphism and TC
      did not develop UMN symptoms during follow-up; neurosurgical correction after the
      appearance of an UMN sign restored normal neurologic and urinary function in all
      children; and untethering in children presenting at birth with UMN symptoms
      resulted in poorer outcome.

PMID- 9633725
TI  - EEG findings in frontal lobe epilepsies.
AB  - As a group, epilepsies of frontal lobe origin are thought to be poorly localized
      using surface EEG recordings. This finding may depend on the specific areas of
      frontal lobe from which the seizures originate or the pathologic substrate. We
      reviewed the presurgical surface EEGs of patients with frontal lobe epilepsy who
      underwent epilepsy surgery. The specific area of the frontal lobe where seizures
      originated was determined by 1) intracranial ictal EEG recordings, or 2) the
      presence of a structural lesion, identified by imaging studies in patients who
      achieved complete seizure control following surgery. We differentiated patients
      whose seizures began in the dorsolateral frontal convexity from those whose
      seizures began in the medial frontal region, and we correlated EEG findings in
      the interictal, postictal, and ictal states with seizure semiology, pathologic
      substrate, and surgical outcome. Four of nine patients had seizures originating
      in the dorsolateral frontal convexity and five had medial frontal onset seizures.
      Patients whose seizures originated from the dorsolateral convexity had focal
      interictal epileptiform abnormalities that localized to the region of seizure
      onset. Patients whose seizures began in the medial frontal region had either no
      interictal epileptiform abnormality or had multifocal epileptiform discharges.
      Patients whose seizures began in the dorsolateral convexity showed focal
      electrographic seizure activity that was localizing. This rhythmic fast activity
      did not appear to be substrate-specific. Patients whose seizure onset localized
      to the medial frontal region did not show focal electrographic seizure at
      clinical onset. We conclude that the scalp EEG recordings of frontal lobe
      epilepsies contain features that enable differentiation of seizures originating
      from two different regions of the frontal lobe.

PMID- 9633726
TI  - Nocturnal temporal lobe epilepsy.
AB  - OBJECTIVE: To analyze clinical, electrophysiologic, and neuroradiologic
      characteristics and prognostic factors in a group of patients with temporal lobe
      epilepsy (TLE) and complex partial seizures (CPS) occurring exclusively or
      predominantly after they fall asleep or before they awaken. BACKGROUND: CPS
      arising during sleep are classically identified with frontal lobe epilepsy. TLE
      associated with seizures occurring only or predominantly during sleep (nocturnal
      TLE) is less common. METHODS: From a series of patients with refractory TLE
      studied between 1980 and 1996, the authors identified 26 patients (15 men) with
      nonlesional nocturnal TLE (mean age, 40 years). Clinical and laboratory
      characteristics of these individuals were studied and compared with a group of 72
      age-matched, randomly selected patients with nonlesional TLE and predominantly
      diurnal seizures (diurnal TLE). RESULTS: Mean age at seizure onset was similar
      for both groups (16.3 versus 18.7 years). In the nocturnal TLE group, 2 of 26
      patients had a positive family history of epilepsy, 18 reported an aura, 4
      presented with CPS in clusters, 11 had unilateral and 15 bilateral temporal EEG
      abnormalities, and 14 of 21 studied had unilateral mesial temporal atrophy. None
      of these factors differed significantly in the two groups except for higher
      frequency of the following in the diurnal TLE group compared with the nocturnal
      TLE group: positive family history for epilepsy (33% versus 8%, p=0.01),
      estimated frequency of seizures (median, 14 versus 2 per month; p < 0.01), and
      presence of antecedent febrile convulsions (33% versus 11%, p=0.04). In the
      nocturnal TLE group, eight patients underwent surgical therapy and became seizure
      free (follow-up, > 12 months). Only two were seizure free on medication.
      CONCLUSIONS: Infrequent and nonclustered seizures, rare family history of
      epilepsy, and low prevalence of childhood febrile convulsions characterize
      nocturnal TLE. Within the TLEs, the nocturnal TLE form seems to have a better
      surgical prognosis.

PMID- 9633727
TI  - A randomized double-blind trial of prednisolone alone or with azathioprine in
      myasthenia gravis. Myasthenia Gravis Study Group.
AB  - We compared prednisolone (PRED) and azathioprine (AZA) versus prednisolone alone
      in the treatment of MG. Prednisolone alone or combined with azathioprine is
      widely used in the treatment of MG, but no randomized placebo-controlled
      comparative trial data are available. The prednisolone dose and clinical outcome
      were compared in a multicenter randomized double-blind study of 34 MG patients
      who were followed up for 3 years. One group (PRED + AZA) received prednisolone
      (on alternate days) plus azathioprine (2.5 mg/kg); the other group received
      prednisolone on alternate days plus placebo (PRED + PLAC). Initial high-dose
      prednisolone (1.5 mg/kg on alternate days) was tapered at remission to the
      minimal dose required to maintain remission. The prednisolone dose did not differ
      significantly between the two groups at 1 year (median values: PRED + AZA, 37.5
      mg on alternate days; PRED + PLAC, 45 mg on alternate days) but was reduced at 2
      and 3 years in the PRED + AZA group (median value at 3 years: PRED + AZA, 0 mg on
      alternate days; PRED + PLAC, 40 mg on alternate days; p=0.02). Relapses and
      failures to remit over the 3 years were more frequent in the PRED + PLAC group.
      There was a sharp rise in the anti-acetylcholine receptor (AChR) titers in the
      PRED + PLAC group at 2 years. Incidence of side effects was slightly less in the
      PRED + AZA group. Azathioprine as an adjunct to alternate day prednisolone in the
      treatment of antibody-positive generalized MG reduces the maintenance dose of
      prednisolone and is associated with fewer treatment failures, longer remissions,
      and fewer side effects.

PMID- 9633728
TI  - Clinical manifestations of mitochondrial DNA depletion.
AB  - OBJECTIVE: We studied five new patients with mitochondrial DNA (mtDNA) depletion
      to better define the clinical spectrum of this disorder. BACKGROUND: mtDNA
      depletion has been associated with myopathy or hepatopathy, or both, in infants
      and young children. Involvement of the CNS and peripheral nervous system has not
      been clearly established. METHODS: We reviewed the clinical course and performed
      morphologic, biochemical, and genetic analyses of muscle samples from five
      patients. RESULTS: Age at onset ranged from 3 months to 5 years, and one patient
      survived until age 10 1/2 years. Two patients had laboratory and clinical
      features reminiscent of dystrophinopathy, two had evidence of brain involvement,
      and two had peripheral neuropathy. Muscle biopsy specimens in all patients showed
      abundant ragged-red fibers. Biochemistry showed cytochrome c oxidase deficiency
      in all patients tested and decreased activities of other respiratory chain
      complexes in some. CONCLUSIONS: Inheritance appeared to be autosomal recessive,
      suggesting that mutations in nuclear DNA are responsible for mtDNA depletion.
      mtDNA depletion should be considered in children with mitochondrial disorders of
      uncertain etiology, and criteria for diagnosis are proposed.

PMID- 9633729
TI  - Epilepsy and mental retardation in a subset of early onset 4q35
      facioscapulohumeral muscular dystrophy.
AB  - The gene for facioscapulohumeral muscular dystrophy (FSHD) has been mapped to
      chromosome 4q35. In most patients with FSHD, a deletion of 3.3 kb tandemly
      repeated units within the EcoRI fragment that can be detected by probe p13E-11 is
      associated with the disease. To elucidate the relation between the phenotype and
      the genotype in FSHD, we examined 91 Japanese unrelated families with a clinical
      diagnosis of FSHD (140 patients, 205 healthy individuals). Of these, 78 families
      (86%) had 4q35-FSHD (127 patients), in which 20 patients (20/127, 16%) were
      classified as early onset FSHD. We found that all nine patients with the smallest
      EcoRI fragments (10 to 11 kb) were classified among the early onset group (9/20,
      45%), and these patients showed a high frequency of both epilepsy (4/9, 44%) and
      mental retardation (8/9, 89%). In contrast, none of the remaining patients with
      4q35-FSHD had epilepsy or mental retardation. We conclude that FSHD patients with
      a large gene deletion in the FSHD gene region tend to have a higher chance of
      showing severe clinical phenotypes with CNS abnormalities. This finding may have
      practical implications for genetic counseling, although the molecular genetic
      background remains unclear.

PMID- 9633730
TI  - Primary hyperparathyroidism and ALS: is there a relation?
AB  - BACKGROUND: An association between primary hyperparathyroidism (PHP) and
      amyotrophic lateral sclerosis (ALS) has been noted; however, a causal relation
      between these disorders has not been confirmed. PATIENTS/METHODS: We report five
      patients (three men, two women) meeting El Escorial criteria for ALS who also had
      PHP. In three patients, the diagnosis of PHP was made during the laboratory
      evaluation for motor neuron disease, and in one patient, the diagnosis of PHP
      preceded the onset of weakness by 5 months and in another by 2 years. Serum
      calcium levels in all five patients were elevated, ranging from 11.2 to 12.8
      mg/dL (normal, <10.4 mg/dL), as were levels of parathyroid hormone (PTH).
      RESULTS: All five patients underwent parathyroid adenoma resection with
      subsequent normalization of serum calcium and PTH levels. Each patient had
      progressive weakness resulting in death 1 to 3 years following parathyroidectomy.
      CONCLUSION: Resection of parathyroid adenomas in patients meeting El Escorial
      criteria for ALS did not alter the course of ALS. PHP and ALS appear to be
      coexisting but unrelated disorders.

PMID- 9633731
TI  - Decreased N-acetylaspartate in motor cortex and corticospinal tract in ALS.
AB  - The primary objectives of this study were to test whether 1) N-acetylaspartate
      (NAA), a neuronal marker, is reduced in motor cortex and corticospinal-tract
      (CST) brain regions of ALS patients; and 2) motor cortex NAA correlates to a
      clinical measurement of upper motor neuron function in ALS patients. Ten probable
      or definite ALS patients and nine neurologically normal control subjects were
      studied. Three axial planes of two-dimensional 1H MRSI data were collected, using
      a single spin-echo multislice sequence (TE140/TR2000). Two of the 1H MRSI planes
      were positioned superior to the lateral ventricles, and one plane was positioned
      at the level of the internal capsule. Spectroscopy voxels were selected from
      motor cortex, frontal cortex, parietal cortex, medial gray matter, centrum
      semiovale white matter, anterior internal capsule, and posterior internal
      capsule. Peak integrals were obtained for the three major 1H MRSI singlet
      resonances, NAA, creatine and phosphocreatine (Cr), and cholines (Cho). Maximum
      finger-tap rate was used as a clinical measurement of upper motor neuron
      function. In ALS, brain NAA/(Cho+Cr) was reduced 19% (p=0.024) in the motor
      cortex and 16% (p=0.021) in the CST (centrum semiovale and posterior internal
      capsule) regions. NAA/ (Cho+Cr) was not reduced in frontal cortex, parietal
      cortex, medial gray matter, or anterior internal capsule. There was a significant
      relation between ALS motor cortex NAA/(Cho+Cr) and maximum finger-tap rate
      (r=0.80; p=0.014). NAA/(Cho+Cr) was reduced in motor cortex and CST regions and
      unchanged in other brain regions of ALS patients when compared with controls.
      These findings are consistent with the known distribution of neuronal loss in
      ALS. The positive correlation between motor cortex NAA/(Cho+Cr) and maximum
      finger-tap rate suggests that reduced NAA/(Cho+Cr) is a surrogate marker of motor
      cortex neuron loss in ALS. These findings support the study of 1H MRSI NAA
      measurement as an objective and quantitative measurement of upper motor neuron
      dysfunction in ALS.

PMID- 9633732
TI  - Neuronal nicotinic ACh receptor antibody in subacute autonomic neuropathy and
      cancer-related syndromes.
AB  - BACKGROUND: Autoantibodies specific for the acetylcholine receptor (AChR) of
      skeletal muscle (containing the alpha1 subunit) impair neuromuscular transmission
      in myasthenia gravis (MG). AChRs mediating fast synaptic transmission through
      autonomic ganglia are structurally similar to muscle AChR, but contain the alpha3
      subunit. We propose that ganglionic AChR autoimmunity may cause dysautonomia.
      OBJECTIVE: To test serum of patients with autonomic neuropathy for autoantibodies
      of neuronal ganglionic AChR specificity. METHODS: We developed an
      immunoprecipitation radioassay by complexing epibatidine (125I-labeled high
      affinity agonist) to a Triton X-100-solubilized AChR antigen from peripheral
      neuroblastoma membranes. Monoclonal rat immunoglobulins (IgG) specific for muscle
      or neuronal AChRs validated the assay's specificity. We tested serum from 52
      healthy subjects, 12 patients with subacute autonomic neuropathy, and 248
      patients with other neurologic disorders. RESULTS: Twelve patients had antibodies
      that bound unequivocally to ganglionic AChR. Five had subacute autonomic
      neuropathy, and three (of six tested) had Isaacs' syndrome; four of these eight
      had a carcinoma (lung, bladder, rectum, thyroid). The remaining four seropositive
      patients (two Lambert-Eaton syndrome, one dementia, one sensory neuronopathy) all
      had Ca2+ channel antibodies and three had small cell lung carcinoma. No healthy
      subject had ganglionic AChR antibodies, nor did 62 patients with MG and muscle
      AChR antibodies. CONCLUSION: Neuronal AChR antibodies are a novel serologic
      marker of neurologic autoimmunity. The pathogenicity of neuronal AChR
      autoantibodies in autonomic neuropathy, Isaacs' syndrome, or other neurologic
      disorders remains to be shown, as has been demonstrated for muscle AChR
      antibodies in MG. An autoimmune and potentially paraneoplastic etiology is
      implicated in seropositive patients.

PMID- 9633733
TI  - Variable progression of HIV-associated dementia.
AB  - A consecutive series of 71 patients diagnosed with HIV-associated dementia (HAD)
      (1984-1994) were studied to characterize the clinical course of HAD, and to
      identify predictive markers of rapid neurologic progression. Neurologic
      progression rate was determined from the change in the Memorial Sloan Kettering
      (MSK) dementia severity score from diagnosis to death. Those with the most rapid
      progression in neurologic disability were compared with those with slow or no
      progression. Autopsy material was immunostained for macrophage activation markers
      and gp41 in 30 individuals. Median survival was 3.3 months and 6.1 months for
      rapid-progression and no-progression patients, respectively. Rapid progression
      was associated with injection drug use but not with race, gender, or age. CD4+
      cell counts were lower at diagnosis among rapid-progression than no-progression
      patients but no differences in AIDS-defining illnesses or patterns of
      antiretroviral therapy were found. At presentation, rapid-progression patients
      had more prominent symptoms of mental slowing than those with no progression;
      however, no other clinical features, CSF, or imaging features distinguished the
      groups. Less abundant macrophage activation in both basal ganglia and midfrontal
      gyrus regions, as judged by HAM56 immunostaining, was noted in 9 no-progression
      patients, compared with 12 rapid-progression patients. Neurologic progression and
      survival with HAD is highly variable. A significant proportion of individuals
      with dementia have prolonged survival of more than 12 months and remain
      cognitively stable. A history of injection drug use and presentation with
      prominent psychomotor slowing is associated with more rapid neurologic
      progression, and these patients tend to show more abundant macrophage activation
      within the CNS.

PMID- 9633734
TI  - Increased cerebral blood volume in HIV-positive patients detected by functional
      MRI.
AB  - OBJECTIVE: To study changes in cerebral hemodynamics related to HIV infection.
      BACKGROUND: Cerebral injury is a well-known manifestation of HIV infection.
      Physiologic changes in the HIV brain may precede structural changes and may be
      detected by functional MRI (fMRI). METHODS: Dynamic contrast fMRI was used to
      measure the cerebral blood volume (CBV) in 13 patients infected with HIV and in 7
      healthy control subjects. RESULTS: Significant increases in dynamic CBV were
      found in the deep (p < 0.001) and cortical gray matter (p < 0.05) of HIV-positive
      (HIV+) patients. Patients with definite cognitive impairment showed significantly
      greater increases in CBV in the deep gray matter (DGM) compared with those
      without impairment. In one patient with rapidly progressive cognitive impairment,
      these abnormalities reversed and paralleled clinical improvement after initiation
      of zidovudine monotherapy. CONCLUSIONS: This study supports the hypothesis that
      HIV infection is associated with significant cerebral hemodynamic changes,
      particularly in the DGM, that may contribute to cognitive dysfunction in AIDS.
      Functional MRI may be useful for early detection of cerebral injury and for the
      assessment of novel therapies.

PMID- 9633735
TI  - M. tuberculosis molecular variation in CNS infection: evidence for strain
      dependent neurovirulence.
AB  - OBJECTIVE: To determine the molecular diversity among Mycobacterium tuberculosis
      isolates associated with central nervous system tuberculosis (CNS TB) in a
      defined cohort of HIV uninfected patients. DESIGN/METHODS: A retrospective
      analysis was performed of clinical and laboratory data for all patients with CNS
      TB diagnosed in Manitoba, Canada, between 1979 and 1996. Restriction fragment
      length polymorphisms (RFLP) of archival isolates of M. tuberculosis from CNS TB
      patients were determined and interpreted against the frequency of different
      isolates from all TB patients in the years 1992 to 1996. RESULTS: Among 2,334
      patients with active TB, CNS TB was diagnosed in 42 (1.8%); meningitis with or
      without tuberculoma in 76%; and tuberculoma alone in 24%. CNS TB patients were
      significantly more likely to be young (<40 years old), female, and of Aboriginal
      origin. Morbidity (fixed/recurrent CNS deficit) rate was 29% and mortality rate
      was 26%. An adverse outcome, either morbidity or mortality, was significantly
      more common in those with meningitis. RFLP analysis of isolates (n=19) from CNS
      TB patients revealed 13 distinct restriction patterns with a predominance of the
      type 1 pattern (n=6). The frequency of type 1 restriction pattern was
      significantly greater in patients with CNS TB compared to all TB patients in
      Manitoba. CONCLUSIONS: CNS TB continues to have a high morbidity and mortality
      despite modern methods of detection and treatment. Although several strains of M.
      tuberculosis cause CNS TB, the current study suggests that the occurrence of CNS
      TB may be strain-dependent.

PMID- 9633736
TI  - Randomized trial comparing two different high doses of methylprednisolone in MS:
      a clinical and MRI study.
AB  - OBJECTIVE: To assess the efficacy of two different high doses of intravenous
      methylprednisolone (IVMP) for the treatment of relapses in MS. BACKGROUND: IVMP
      is the treatment of choice for MS relapses, but it is unknown whether its effects
      are dose related. METHODS: We conducted a double-blind, randomized study. Follow
      up included serial clinical and MRI recordings at baseline and at 7, 15, 30, and
      60 days after the beginning of treatment. Outcome measures were the number of
      brain and cervical spinal cord MRI contrast-enhancing lesions, and the Expanded
      Disability Status Scale score. RESULTS: Both treatment regimens improved clinical
      scores and reduced the number of MRI enhancing lesions during the follow-up
      period. The higher dose of IVMP was significantly more effective than the lower
      dose in reducing the number of MRI contrast-enhanced lesions at 30 and 60 days,
      mainly by decreasing the rate of new lesion formation. CONCLUSIONS: The higher
      dosage of IVMP has a more powerful and prolonged action in maintaining blood
      brain barrier integrity after a clinical relapse.

PMID- 9633737
TI  - Efficacy of oxycodone in neuropathic pain: a randomized trial in postherpetic
      neuralgia.
AB  - OBJECTIVE: Although opioid analgesics are used in the management of neuropathic
      pain syndromes, evidence of their efficacy remains to be established. We
      evaluated the clinical efficacy and safety of oxycodone in neuropathic pain using
      postherpetic neuralgia as a model. METHODS: Patients with postherpetic neuralgia
      of at least moderate intensity were randomized to controlled-release oxycodone 10
      mg or placebo every 12 hours, each for 4 weeks, using a double-blind, crossover
      design. The dose was increased weekly up to a possible maximum of 30 mg every 12
      hours. Pain intensity and pain relief were assessed daily, and steady (ongoing)
      pain, brief (paroxysmal) pain, skin pain (allodynia), and pain relief were
      recorded at weekly visits. Clinical effectiveness, disability, and treatment
      preference were also assessed. RESULTS: Fifty patients were enrolled and 38
      completed the study (16 men, 22 women, age 70+/-11 years, onset of postherpetic
      neuralgia 31+/-29 months, duration of pain 18+/-5 hours per day). The oxycodone
      dose during the final week was 45+/-17 mg per day. Compared with placebo,
      oxycodone resulted in pain relief (2.9+/-1.2 versus 1.8+/-1.1, p=0.0001) and
      reductions in steady pain (34+/-26 versus 55+/-27 mm, p=0.0001), allodynia (32+/
      26 versus 50+/-30 mm, p=0.0004), and paroxysmal spontaneous pain (22+/-24 versus
      42+/-32 mm, p=0.0001). Global effectiveness, disability, and masked patient
      preference all showed superior scores with oxycodone relative to placebo (1.8+/
      1.1 versus 0.7+/-1.0, p=0.0001; 0.3+/-0.8 versus 0.7+/-1.0, p=0.041; 67% versus
      11%, p=0.001, respectively). CONCLUSIONS: Controlled-release oxycodone is an
      effective analgesic for the management of steady pain, paroxysmal spontaneous
      pain, and allodynia, which frequently characterize postherpetic neuralgia.

PMID- 9633738
TI  - Double-blind randomized trial of tramadol for the treatment of the pain of
      diabetic neuropathy.
AB  - OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of
      tramadol in treating the pain of diabetic neuropathy. BACKGROUND: The pain of
      diabetic neuropathy is a major cause of morbidity among these patients and
      treatment, as with other small-fiber neuropathies, is often unsatisfactory.
      Tramadol is a centrally acting analgesic for use in treating moderate to
      moderately severe pain. METHODS: This multicenter, outpatient, randomized, double
      blind, placebo-controlled, parallel-group study consisted of a washout/screening
      phase, during which all analgesics were discontinued, and a 42-day double-blind
      treatment phase. A total of 131 patients with painful diabetic neuropathy were
      treated with tramadol (n=65) or placebo (n=66) tramadol, which were administered
      as identical capsules in divided doses four times daily. The primary efficacy
      analysis compared the mean pain intensity scores in the tramadol and placebo
      groups obtained at day 42 of the study or at the time of discontinuation.
      Secondary efficacy assessments were the pain relief rating scores and a quality
      of life evaluation based on daily activities and sleep characteristics. RESULTS:
      Tramadol, at an average dosage of 210 mg/day, was significantly (p < 0.001) more
      effective than placebo for treating the pain of diabetic neuropathy. Patients in
      the tramadol group scored significantly better in physical (p=0.02) and social
      functioning (p=0.04) ratings than patients in the placebo group. No statistically
      significant treatment effects on sleep were identified. The most frequently
      occurring adverse events with tramadol were nausea, constipation, headache, and
      somnolence. CONCLUSIONS: The results of this placebo-controlled trial showed that
      tramadol was effective and safe in treating the pain of diabetic neuropathy.

PMID- 9633739
TI  - Philadelphia Infirmary for Nervous Diseases: America's original model of
      institutional neurology.
AB  - The role and contributions of the Philadelphia Orthopedic Hospital and Infirmary
      for Nervous Diseases in the development of neurology in 19th-century America are
      described. American neurology was largely born during the Civil War through the
      work of S.W. Mitchell at Turner's Lane Hospital. With the closing of this
      military facility, the United States was left without an institution dedicated to
      neurologic research and the treatment of nervous system diseases. Nineteenth
      century archival data, including original Trustees' minutes, annual board of
      managers reports, patient case books, and published research from the
      Philadelphia Orthopedic Hospital and Infirmary for Nervous Diseases were studied.
      The Philadelphia Orthopedic Hospital and Infirmary for Nervous Diseases promoted
      the development of neurology in the United States through three main activities.
      First, it offered patients with primary nervous system diseases, arthritis, and
      orthopedic disorders specialized care that was unavailable at medical
      universities. Second, its medical staff, especially Mitchell, provided
      opportunities for advanced neurologic education. Postgraduate physicians
      interested in neurologic disease attended formal lectures and directly
      participated in the operation of outpatient clinics and inpatient rounds.
      Finally, its formalized record system in the form of case books facilitated
      neurologic research. These records formed the basis of landmark publications by
      Mitchell, Sinkler, Osler, and others on rest therapy, spastic palsies, chorea,
      and other topics. As America's first and comprehensive peacetime neurologic
      facility, the Philadelphia Orthopedic Hospital and Infirmary for Nervous Diseases
      fostered the evolution of neurology as a separate, viable specialty in the post
      Civil War period and provided a particular focus for the study of interactions
      among orthopedic, nutritional, and neurologic disorders.

PMID- 9633740
TI  - Spontaneous intracranial hypotension resulting in stupor caused by diencephalic
      compression.
AB  - A 51-year-old man had a 4-month history of progressive headache and gradual onset
      of somnolence. MRI suggested spontaneous intracranial hypotension (SIH) with
      diencephalic compression, but he did not improve after three epidural blood
      patches. He became alert following intrathecal saline infusion that normalized
      his CSF pressure. A CSF leak was noted on spinal MRI and confirmed with CT
      contrast myelography. Surgical ligation of a torn dural root sleeve isolating a
      ruptured Tarlov's cyst resulted in permanent cure.

PMID- 9633741
TI  - Hemopericardium and cardiac tamponade after thrombolysis for acute ischemic
      stroke.
AB  - Hemorrhage is the major complication of IV recombinant tissue plasminogen
      activator (rt-PA) treatment for stroke. We report three patients with mild or
      indistinct cardiac symptoms prior to thrombolysis in whom hemodynamically
      significant cardiac tamponade occurred after treatment with rt-PA. Acute ischemic
      stroke patients may have undetected myocardial or pericardial disease that may
      pose a risk for hemopericardium and life-threatening tamponade after treatment
      with rt-PA.

PMID- 9633742
TI  - Isolated voluntary facial paresis due to pontine ischemia.
AB  - We describe a patient with isolated voluntary facial paresis due to a unilateral
      lacunar lesion in the contralateral mediodorsal middle base of the pons.
      Transcranial magnetic stimulation confirmed the involvement of supranuclear
      corticofacial tract fibers and sparing of the corticolingual and corticospinal
      connections. This observation demonstrates that the fibers conveying voluntary
      orofacial activation descend mediodorsally at the level of the middle pons and
      that the fibers conveying emotional activation may be assumed to converge below
      this level.

PMID- 9633743
TI  - Giant cell arteritis and Vernet's syndrome.

PMID- 9633744
TI  - Upper cervical myelopathy associated with low CSF pressure: a complication of
      ventriculoperitoneal shunt.
AB  - A patient who had undergone ventriculoperitoneal shunting developed upper
      cervical myelopathy. His CSF pressure was markedly low, and deformation of the
      spinal cord and shrinkage of the subarachnoid space at the upper cervical level
      were found in radiologic examinations. Ligation of the shunt tube resulted in
      almost complete recovery. The effect of excessive drainage may have caused the
      abnormalities.

PMID- 9633745
TI  - Congenital bilateral perisylvian polymicrogyria presenting as congenital
      hemiplegia.
AB  - We report three children with pure congenital hemiplegia found to have congenital
      bilateral perisylvian polymicrogyria (CBPP). None of our patients had the
      seizures, oromotor dysfunction, or cognitive impairment usually associated with
      CBPP. CBPP may be more common and heterogeneous than previously thought, is
      easily recognized by MRI, and should be included in the differential diagnosis of
      the young child presenting with congenital hemiplegia.

PMID- 9633746
TI  - CSF levels of carnitine in children with meningitis, neurologic disorders, acute
      gastroenteritis, and seizure.
AB  - Carnitine concentrations in CSF, serum, and urine in normal febrile children and
      children with meningitis, neurologic disorders, and dehydration were studied.
      Carnitine levels in CSF were 1/10 compared with serum in normal febrile children.
      These levels increased two- to three-fold in the pathologic conditions studied.
      Since damage to the blood-brain barrier occurs in these conditions, higher blood
      brain barrier permeability might explain CNS carnitine accumulation.

PMID- 9633747
TI  - Creutzfeldt-Jakob disease (CJD) after blood product transfusion from a donor with
      CJD.
AB  - We report a second case of an association between an albumin transfusion and
      Creutzfeldt-Jakob disease. On balance, we believe our case represents a chance
      and not a causal relation.

PMID- 9633748
TI  - Cefuroxime-induced encephalopathy.
AB  - We describe four patients who developed an encephalopathic syndrome characterized
      by obtundation or stupor, myoclonic jerks, and asterixis in association with
      cefuroxime therapy. Three patients had renal failure. These cases suggest that
      cefuroxime in overdose or in conventional doses in patients with renal failure
      can cause a reversible encephalopathy. This syndrome may have been unrecognized
      because it usually occurs in severely ill patients with additional causes for
      encephalopathy.

PMID- 9633749
TI  - A new mitochondrial tRNA(Met) gene mutation in a patient with dystrophic muscle
      and exercise intolerance.
AB  - A 30-year-old woman with a novel heteroplasmic U4409C mtDNA mutation in the
      tRNA(Met) gene presented with growth retardation, muscle weakness, severe
      exercise intolerance, and lactic acidosis. Muscle biopsy showed unusually severe
      dystrophic features. The mutation was not present in maternal relatives or 25
      healthy subjects. Single-fiber PCR-RFLP analysis of mtDNA showed higher
      proportion of the mutation in COX-negative than in COX-positive muscle fibers.

PMID- 9633750
TI  - MRI in juvenile ALS: a patient report.
AB  - We describe the MR images of a patient with juvenile ALS. MRI of the brain showed
      bilateral hyperintensities along the corticospinal tracts extending from the
      corona radiata to the brainstem on T2-weighted images. These findings should be
      differentiated from the slight hyperintensities seen in the posterior limbs of
      the internal capsules in normal subjects.

PMID- 9633751
TI  - Electrophysiological aids in distinguishing organic from psychogenic tremor.
AB  - The clinical differentiation of tremors of organic and psychogenic origin can be
      difficult. We describe a patient with unilateral upper limb tremor that was
      initially considered to have a psychogenic cause, but subsequent frequency
      analysis of EMG signals and accelerometer recordings indicated that the tremor
      was organic in nature. An ischemic lesion in the contralateral lentiform nucleus
      found on MRI supported this conclusion. Quantitative electrophysiologic studies
      may thus be useful in distinguishing organic from psychogenic tremor.

PMID- 9633752
TI  - High prevalence of parkinsonism after occupational exposure to lead-sulfate
      batteries.
AB  - Seven of nine postal workers exposed to lead-sulfate batteries over a period of
      up to 30 years developed parkinsonian symptoms. One of the remaining two showed
      left-hand bradykinesia and one was not available for examination. The high
      prevalence and cause of parkinsonism in these patients remains unexplained. Lead
      intoxication may play a role in the occurrence of parkinsonian symptoms, but
      involvement of sulfate and other sulfur compounds must also be considered.

PMID- 9633753
TI  - The brainstem and thalamic lesions in dentatorubral-pallidoluysian atrophy: an
      MRI study.
AB  - We studied the frequency and characteristics of brainstem and thalamic lesions in
      dentatorubral-pallidoluysian atrophy using MRI. Of 15 subjects diagnosed by DNA
      analysis, 13 had lesions in the pontine base, nine in the midbrain, and five in
      the thalamus. Lesions were correlated positively with the patient's age, but not
      with neurologic features or numbers of CAG repeats. Patients with Machado-Joseph
      disease or spinocerebellar ataxia 1 did not show these characteristic lesions.

PMID- 9633754
TI  - Mood response to levodopa infusion in early Parkinson's disease.
AB  - Mood response to levodopa infusion was studied in 18 Parkinson's disease (PD)
      patients during the first year of levodopa therapy before and after 2-hour (1.0
      mg/kg/h) levodopa infusions at baseline and 6- and 12-month follow-up. Mood
      elevation was greatest after a 2-day levodopa holiday at the 6- and 12-month
      assessments. Age, sex, duration and severity of PD, and ongoing oral levodopa
      dose did not correlate with mood response. Mood response in these patients
      differs from that seen in advanced patients, possibly because of sensitization to
      levodopa's mood effects.

PMID- 9633755
TI  - Unusual ocular motility disturbances with increased intracranial pressure.
AB  - We evaluated nine patients with external ophthalmoparesis and increased
      intracranial pressure. The eye movements normalized when the intracranial
      pressure was controlled. Investigations for an underlying cause of elevated
      cerebrospinal fluid pressure are warranted when ocular motility disorders are
      present.

PMID- 9633756
TI  - Visual activation patterns in patients with optic neuritis: an fMRI pilot study.
AB  - We studied the use of functional MRI (fMRI) with visual stimulation in nine
      patients with unilateral optic neuritis. Eight healthy subjects served as
      controls. Patients showed reduced activation upon stimulation of the affected
      eye, on average 33% (range 0 to 156%) of the average monocular activation in the
      control group. Decreased activation was also seen for the unaffected eye (61% of
      control values, range 3 to 133%). We conclude that fMRI with visual stimulation
      is feasible in patients with optic neuritis and deserves future study.

PMID- 9633757
TI  - Alpha tocopherol in CSF of subjects taking high-dose vitamin E in the DATATOP
      study. Parkinson Study Group.
AB  - Alpha-Tocopherol concentrations were determined in the CSF of patients with early
      untreated Parkinson's disease receiving 2,000 IU vitamin E orally per day. After
      treatment the concentrations increased significantly (p < 0.001) by 76+/-10
      (SE)%. The net increases in CSF alpha-tocopherol concentrations after treatment
      showed a significant positive correlation with the number of days of vitamin E
      ingestion (p < 0.001). Thus, high-dose vitamin E treatment results in elevating
      CSF vitamin E levels and possibly brain vitamin E levels.

PMID- 9633758
TI  - Unilateral neglect: a common but heterogeneous syndrome.
AB  - The neglect syndrome is a cluster of neurologic symptoms commonly found after
      right hemisphere damage. This study investigates the degree of association
      between the main components in a representative sample of 69 patients at 2 to 3
      days poststroke. Despite evidence of statistically significant associations
      between components, many dissociations were found, indicating that neglect is a
      highly heterogeneous condition.

PMID- 9633759
TI  - Confirmation of an association between a polymorphism in exon 3 of the low
      density lipoprotein receptor-related protein gene and Alzheimer's disease.
AB  - C766T, a polymorphism in exon 3 of the gene for the low-density lipoprotein
      receptor-related protein (LRP), was found to be associated with late-onset
      Alzheimer's disease (AD). We developed a PCR-restriction enzyme-based assay to
      analyze this allele in 234 AD patients and 103 controls. We confirmed that the
      LRP C766T polymorphism was in disequilibrium with AD--the C/C genotype was
      present in 76% of AD patients and 60% of controls (p < 0.01); however, the LRP
      polymorphism did not influence age at onset of AD.

PMID- 9633760
TI  - Root stimulation studies in the evaluation of patients with motor neuron disease.
AB  - Nerve root stimulation may be employed in patients with motor neuron disease
      (MND) to rule out motor neuropathy with conduction block. The diagnostic utility
      of these studies is unknown, in part because the range of amplitude changes
      across nerve root segments in patients with active neuronal degeneration has not
      been well studied. We reviewed root stimulation studies in 32 patients (59
      nerves) with MND and found segmental amplitude reduction from 0 to 45%, a range
      similar to values reported for normal subjects; there was no suggestion of
      conduction block based on our usual criteria.

PMID- 9633761
TI  - Low-dose steroids reduce flu-like symptoms at the initiation of IFNbeta-1b in
      relapsing-remitting MS.
AB  - To determine whether low-dose prednisone reduces flu-like symptoms at the
      initiation of interferon beta 1-b (IFNbeta-1b), we studied 71 patients with
      clinically definite, relapsing-remitting multiple sclerosis who were started on
      IFNbeta-1b. Patients were randomized to receive prednisone plus paracetamol or
      only paracetamol and were monitored for side effects. Systemic side effects were
      minimal in the steroid group compared with the nonsteroid group during the first
      15 days of treatment (p=0.005). At 3 months, both groups showed a similar
      frequency of flu-like symptoms. No differences in local reaction between the two
      groups were observed throughout the study.

PMID- 9633762
TI  - Neuroacanthocytosis and aprebetalipoproteinemia.
AB  - A 30-year-old woman presented with a progressive neurologic disorder
      characterized by seizures, buccolingual dyskinesias, orofacial tics, choreiform
      movements, atrophy, and areflexia. Investigations revealed normal lipid profile
      except for aprebetalipoproteinemia. Phase-contrast and electron microscopy showed
      35 to 40% acanthocytes. MRI and 18fluorodeoxyglucose-PET studies showed caudate
      atrophy and hypometabolism. The phenotype of this patient is neuroacanthocytosis
      and its association with aprebetalipoproteinemia may represent a new subentity of
      the disorder.

PMID- 9633763
TI  - Progressive facial hemiatrophy: abnormality of intracranial vasculature.
AB  - Progressive facial hemiatrophy (PFH) or Parry-Romberg syndrome is associated with
      ipsilateral brain lesions and neurologic symptoms. We describe a 35-year-old man
      with PFH and frequent hemiplegic migraine. On cerebral angiography, reversible
      vessel caliber changes were seen within the symptomatic hemisphere. An
      abnormality of the intracranial vasculature may be present in some patients with
      PFH and neurologic manifestations.

PMID- 9633764
TI  - Petroclival meningioma presenting with pathological laughter.

PMID- 9633765
TI  - Absence of HuD gene mutations in paraneoplastic small cell lung cancer tissue.

PMID- 9633766
TI  - Matrix metalloproteinase 9 (gelatinase B) in cerebrospinal fluid of HTLV-1
      infected patients with tropical spastic paraparesis.

PMID- 9633767
TI  - Levodopa in human breast milk: clinical implications.

PMID- 9633768
TI  - Acute transverse myelitis associated with tuberculin skin test (PPD).

PMID- 9633769
TI  - Possible postherpetic neuralgia first occurring seven years after herpes zoster.

PMID- 9633770
TI  - Wegener's granulomatosis presenting with bulbar palsy and bilateral jugular vein
      compression.

PMID- 9633771
TI  - Delayed diagnosis of Friedreich's ataxia due to coexisting recessive deaf/blind
      syndrome.

PMID- 9633772
TI  - Facial weakness in hereditary inclusion body myopathies.

PMID- 9633773
TI  - Hypoglossal nerve palsy associated with deep cervical lymphadenopathy.

PMID- 9633774
TI  - Are carotid endarterectomy complication rates being monitored?

PMID- 9633775
TI  - Resolution of a brainstem abscess through antituberculosis therapy.

PMID- 9633776
TI  - Medicare's resource-based relative value scale.

PMID- 9633777
TI  - Anticytokine antibodies in beta-interferon-treated patients.

PMID- 9633778
TI  - Anticytokine antibodies in beta-interferon-treated patients.

PMID- 9633779
TI  - A 44-month clinical-brain MRI follow-up in a patient with B12 deficiency.

PMID- 9633780
TI  - Acute intermittent porphyria.

PMID- 9633781
TI  - Association of Ginkgo biloba with intracerebral hemorrhage.

PMID- 9633782
TI  - Electrocerebral inactivity associated with obstructive sleep apnea.

PMID- 9633783
TI  - Radiotherapy at tumor recurrence in primary CNS lymphoma.

PMID- 9633784
TI  - Benign paroxysmal positioning vertigo.

PMID- 9633785
TI  - Electrophysiologic findings in multifocal motor neuropathy.

PMID- 9633786
TI  - Lack of association between blood pressure variability and left ventricular mass
      in essential hypertension.
AB  - Blood pressure (BP) variability could induce detrimental effects on left
      ventricular (LV) structure in hypertension. We investigated the association
      between short-term BP variability, assessed with 24-h noninvasive ambulatory BP
      monitoring, and LV mass at echocardiography in 1822 untreated subjects (953 men,
      869 women) with essential hypertension (EH). The standard deviation (SD) of
      daytime and night-time systolic BP (SBP, r = 0.13/0.10; both P < .001), but not
      of diastolic BP, showed a weak correlation with LV mass. Because the SD of
      daytime SBP showed a direct association with average 24-h SBP (r = 0.27),
      subjects were ranked into quartiles of the distribution of 24-h SBP. For each
      quartile, the subjects with SD of daytime (and night-time) SBP below or above the
      median were classified at low or high BP variability. In both genders, subjects
      with high daytime SBP variability were older than those at low variability (both
      P < .01). Within each quartile, LV mass did not differ between the groups at low
      v those at high SBP variability. Overall, age-adjusted LV mass index was 115 and
      115 g/m2 in men at low and high daytime SBP variability (P = .84), and 116 and
      114 g/m2 in men at low and high nighttime SBP variability (P = .31). The
      corresponding values in women were 98 and 99 g/m2 (P = .53) and 98 and 99 g/m2 (P
      = .64). In conclusion, when the effects of age, gender, and average 24-h BP are
      taken into account, short-term BP variability assessed with noninvasive
      monitoring is unrelated to LV mass in subjects with EH.

PMID- 9633787
TI  - Heart rate variability and baroreflex sensitivity in hypertensive subjects with
      and without metabolic features of insulin resistance syndrome.
AB  - Both abnormal autonomic control of heart rate, assessed by heart rate variability
      (HRV) and baroreflex sensitivity (BRS), and insulin resistance syndrome are
      common in hypertensive patients. It is not known, however, whether abnormalities
      in HRV and BRS in hypertension are related to the insulin-resistance syndrome.
      Therefore, we compared HRV and BRS in hypertensive subjects with and without
      metabolic features of the insulin-resistance syndrome. HRV was analyzed using the
      autoregressive method from a 45-min electrocardiographic recording (15 min lying,
      sitting, and standing) and BRS using the Valsalva maneuver. The groups were
      matched for age, sex, and antihypertensive medication, and age- and sex-matched
      normotensive subjects served as a control group (n = 69 in each group). The
      insulin-resistance syndrome was defined using the criteria of 1) hypertension
      (blood pressure >160/90 mm Hg), 2) hypertriglyceridemia (fasting serum
      triglycerides > or =2.0 mmol/L), and 3) hyperinsulinemia (fasting serum insulin >
      or =12 mU/L). Standard deviation of RR intervals, total, very-low-, and low
      frequency power of HRV were significantly lower in hypertensive subjects with
      insulin-resistance syndrome compared to hypertensive subjects without the
      syndrome and to normotensive controls (P < .001 for all), but the hypertensive
      group without the syndrome did not differ from the normotensive group. High
      frequency power of HRV (P < .01) and BRS (P < .05) were reduced in both
      hypertensive groups compared to the normotensive group. In multiple regression
      analysis, systolic blood pressure (P < .01) and serum triglyceride level (P <
      .001) were independent predictors of reduced total power of HRV, but BRS was
      related only to systolic blood pressure (P < .01). Thus, most of the
      abnormalities in overall HRV seem to be confined to the subgroup of hypertensive
      subjects with insulin-resistance syndrome, but baroreflex and respiratory
      modulation of heart rate are impaired also in hypertensive subjects without
      metabolic features of insulin-resistance syndrome.

PMID- 9633788
TI  - Relationship between blood pressure variability and serum dehydroepiandrosterone
      sulfate levels.
AB  - Decreased diurnal blood pressure variability and low dehydroepiandrosterone
      sulfate (DHEAS) levels are important predictors of cardiovascular morbidity and
      mortality. The aim of the study was to determine the relationship between DHEAS
      levels and diurnal blood pressure variability in normotensive subjects and in
      patients with essential hypertension of both genders. An ambulatory blood
      pressure monitor (ABPM), Meditech O2 device and radioimmunoassay were used for
      ambulatory blood pressure monitoring and the determination of DHEAS levels,
      respectively. A close correlation (P < .001) was found between the diurnal
      indices and plasma DHEAS levels of the 387 subjects (86 normotensive and 301
      hypertensive patients) participating in the study. Decreased plasma DHEAS levels
      were associated in both genders, and in both normotensive and hypertensive
      patients with significantly (P < .001) lower diurnal indices. There was a close
      correlation (P < .001) between the age-related decrease in plasma DHEAS levels
      and diurnal indices in both genders. Systolic and diastolic blood pressure
      variability changed parallel to plasma DHEAS levels in both genders, whether
      hypertension was present or not. Additional investigations are needed to find out
      whether reduced DHEAS levels play a role in decreased diurnal indices or whether
      both can be traced back to one and the same cause.

PMID- 9633789
TI  - Blood pressure and heart rate in young thalassemia major patients.
AB  - The analysis of blood pressure (BP) and heart rate (HR) variability is currently
      used to investigate the mechanisms responsible for cardiovascular control;
      therefore, we assessed whether an impairment of 24-h BP and HR profiles and
      sympathovagal interaction modulating cardiovascular function was present in
      patients with thalassemia major (TM) in preclinical phase of heart disease. Nine
      beta-thalassemic patients 18 years old without clinical signs of cardiac failure
      and 9 age- and sex-matched controls were studied. Twenty-four-hour-ambulatory BP
      and HR were measured using the SpaceLabs 90207 device. A truncated Fourier series
      with four harmonics was used to describe the diurnal blood pressure profile. Mean
      24-h ambulatory systolic BP, diastolic BP, and mean arterial pressure were
      significantly lower in TM patients than in normal subjects (P < .05). A
      significantly higher nighttime HR value was found in TM patients (P < .05). More
      than 40% of the TM patients did not show a significant diurnal BP and HR rhythm.
      In TM patients, the overall amplitude of systolic BP, diastolic BP, and HR was
      significantly lower than in controls (P < .01). The night/day differences of
      systolic BP, diastolic BP, and HR were significantly lower in TM patients than in
      normals (P < .01). Furthermore, we performed power spectral analysis on short
      term continuous finger BP and HR data in supine position and during passive head
      up tilt. Total spectral power of systolic BP was significantly lower in patients
      than controls (P < .05). Low-frequency (LF) power of systolic BP and diastolic BP
      and LF/high-frequency (HF) ratio of HR were significantly lower during tilt in TM
      patients compared to controls (P < .05). High-frequency power of HR was
      significantly higher in patients than controls (P < .05). The baroreflex gain
      assessed by alpha-index was the same in supine position but was higher in TM
      patients during passive tilt (P < .05). An inverse relationship between LF/HF
      ratio of HR and hemoglobin levels in TM patients was found. Finally, plasma
      norepinephrine levels were significantly lower in thalassemics (P < .005). In
      young TM patients in a preclinical stage of heart disease, these findings
      demonstrated abnormal 24-h BP and HR rhythms and a decreased short-term
      variability of BP and HR, in particular in the LF range, showing a diminished
      sympathetic activity.

PMID- 9633790
TI  - Changes of plasma endothelin and growth factor levels, and of left ventricular
      mass, after chronic AT1-receptor blockade in human hypertension.
AB  - The stimulation of autocrine and paracrine factors such as basic fibroblast-
      (bFGF) and platelet-derived (PDGF) growth factors mediates many of the growth
      promoting actions of angiotensin II. The aim of this study was to evaluate the
      effect of chronic AT1-receptor blockade on plasma endothelin-1 (ET-1) and growth
      factors levels, and on left ventricular mass, in essential hypertension (EH). The
      study population consisted of 16 patients with mild-moderate EH, and 25
      normotensive controls. In the EH patients under basal conditions, and after 3 and
      6 months of chronic therapy with Losartan 50 mg/day, we measured serum levels of
      ET-1, bFGF and PDGF, and tumor necrosis factor (TNF). At the same time, all
      patients underwent 24-h ambulatory blood pressure monitoring and an
      echocardiographic evaluation to measure the thickness of the posterior wall (PWT)
      of the left ventricle and of the interventricular septum (IVS). The healthy
      controls underwent the same analyses, under basal conditions, at baseline and
      after 3 and 6 months of observation. In the EH patients, after 3 months of AT1
      receptor blockade bFGF was reduced from 13.6 +/- 0.7 to 10.9 +/- 0.7 pg/mL (P <
      .004), and both TNF and PDGF were significantly decreased (P < .006 and P < .007,
      respectively). After 6 months of therapy, ET-1 was significantly diminished in
      comparison with baseline (6.9 +/- 0.8 v 5.5 +/- 0.1 fmol/mL; P < .05), and the
      reduction in the levels of growth factors were even more significant than at 3
      months of treatment. Both PWT and IVS were significantly changed after 6 months
      of therapy with losartan after basal evaluation (P < .05, respectively). Systolic
      and diastolic 24-h blood pressures declined significantly after 3 and 6 months of
      therapy with losartan (P < .01, respectively). It seems likely that the
      inhibition of the action of angiotensin II by the specific AT1-receptor blockade,
      by reducing circulating levels of ET-1 and those of some growth factors, may
      offer an advantage regarding the effect on hypertensive cardiovascular changes in
      human hypertension.

PMID- 9633791
TI  - Effect of chronic treatment with two different ET(A) selective endothelin
      receptor antagonists on blood pressure and small artery structure of
      deoxycorticosterone acetate (DOCA)-salt hypertensive rats.
AB  - Chronic treatment with a combined ET(A) and ET(B) endothelin receptor antagonist
      blunts hypertension development and small artery hypertrophy in
      deoxycorticosterone acetate (DOCA)-salt treated rats, in which endothelin-1 is
      overexpressed in endothelial cells of blood vessels. To determine whether ET(A)
      receptor antagonism played a predominant role in these findings, in this study
      the effects of two orally active ET(A) selective endothelin receptor antagonists,
      A-127722.5 and LU 135252, were evaluated on blood pressure and small artery
      structure in DOCA-salt hypertensive rats. Rats received A-127722.5 (30 mg/kg/day)
      or LU 135252 (50 mg/kg/day) in their drinking water since induction of
      hypertension. Whereas three of 10 untreated DOCA-salt hypertensive rats died, in
      the two treated groups none died and all appeared healthier. Systolic blood
      pressure of treated DOCA-salt hypertensive rats, measured with the tail cuff
      method, was lower than that of untreated DOCA-salt hypertensive rats by a mean of
      20 mm Hg (P < .01) after 4 weeks of treatment with A-127722.5 and by 14 mm Hg (P
      < .01) with LU 135252. Cardiac and aortic relative weights were unaffected by
      treatment with either agent. Small arteries of the mesenteric, coronary, renal,
      and femoral vasculature, examined under standardized conditions after mounting on
      a wire myograph, were found to exhibit significant inward hypertrophic remodeling
      in DOCA-salt hypertensive rats. DOCA-salt hypertensive rats treated with A
      127722.5 had a significantly smaller media width and media-to-lumen ratio in the
      four vascular beds examined, and rats treated with LU 135252 showed these
      findings in mesenteric and renal small arteries. These results demonstrate that
      chronic ET(A) selective antagonism induces similar effects to those of combined
      ET(A)/ET(B) receptor antagonists in DOCA-salt hypertensive rats; namely, mild
      reduction in development of hypertension and blunting of small artery
      morphological changes, and also appears to improve survival. These results
      suggest a role of ET(A) receptors in the endothelin dependent component of blood
      pressure elevation in DOCA-salt hypertensive rats, and in the small artery
      morphological changes present in this model of experimental hypertension.

PMID- 9633792
TI  - Reduction of capillary permeability in the fructose-induced hypertensive rat.
AB  - Impaired insulin transcapillary transport and the subsequent decrease in insulin
      delivery to target organs have been suggested to play a role in insulin
      resistance. These defects were studied in fructose-fed rats, an animal model with
      insulin resistance. For this study, male Sprague-Dawley rats were fed with either
      a 60% fructose enriched (F) or a standard chow diet (N) for a total of 2, 4, or 8
      weeks. Capillary permeability to albumin was assessed at the end of each dietary
      period by quantifying the extravasation of albumin-bound Evans blue (EB) dye in
      different organs. Unanesthetized animals were injected with Evans blue dye (20
      mg/kg) in the caudal vein 10 min before being killed and EB dye was extracted by
      formamide from selected organs collected after exsanguination. As expected, rats
      had an increase in blood pressure upon feeding with fructose at 4 and 8 weeks (F,
      149 +/- 3 mm Hg; N, 139 +/- 3 mm Hg; P < .05). Using this technique, we showed a
      56% and a 51% reduction in capillary permeability in skeletal muscles at 4 and 8
      weeks of fructose feeding, respectively (4 weeks: N, 44.5 +/- 5.0 microg/g of dry
      tissue; F, 19.8 +/- 4.2 microg/g of dry tissue; P < .01 and 8 weeks: N, 23.3 +/-
      3.7 microg/g of dry tissue; F, 11.3 +/- 4.0 microg/g of dry tissue; P < .05).
      Similar changes were observed at 4 weeks in the thoracic aorta (N, 82.8 +/- 8.8
      microg/g of dry tissue; F, 53.0 +/- 5.1 microg/g of dry tissue; P < .02) and skin
      (N, 36.0 +/- 5.3 microg of dry tissue; F, 15.0 +/- 2.3 microg/g of dry tissue; P
      < .02) and at 8 weeks in the liver (N, 107.5 +/- 4.3 microg/g of dry tissue; F,
      80.9 +/- 3.2 microg/g of dry tissue; P < .01). In conclusion, fructose feeding is
      accompanied by a significant and selective reduction of Evans blue leakage
      primarily in skeletal muscle and liver, and transiently in the skin and aorta,
      consistent with a role for decreased tissue insulin delivery in insulin
      resistance.

PMID- 9633793
TI  - Renal uptake of circulating angiotensin II in Val5-angiotensin II infused rats is
      mediated by AT1 receptor.
AB  - Previous studies have demonstrated that augmentation of intrarenal angiotensin II
      (ANG II) levels during ANG II induced hypertension involves both endogenous
      formation and accumulation of circulating ANG II. The present work extends these
      findings and determines whether accumulation of infused ANG II in the kidney
      requires AT1 receptor activation by using Val5-ANG II as the infused peptide.
      Male Sprague-Dawley rats were uninephrectomized and divided into three groups:
      control (n = 6), Val5-ANG II (exogenous form) infused (n = 8), and Val5-ANG II
      infused rats treated with losartan (n = 8). Val5-ANG II, which has the same
      biological and immunoreactive properties as endogenous ANG II, was infused at 40
      ng/min via an osmotic minipump implanted subcutaneously. By day 12, systolic
      blood pressure (SBP) increased significantly in Val5-ANG II infused rats (197 +/-
      7 mm Hg). As previously shown, the development of hypertension in ANG II infused
      rats was prevented by losartan treatment. Blood and kidney samples were
      harvested, subjected to HPLC to separate Val5-ANG II (exogenous) from Ile5-ANG II
      (endogenous) and the fractions were measured by radioimmunoassay. In the Val5-ANG
      II infused rats treated with losartan, total plasma ANG II levels were elevated
      to a greater extent than in rats not treated with losartan (289 +/- 20 v 119 +/-
      14 fmol/mL). However, losartan markedly decreased by 88% the enhancement of
      intrarenal Val5-ANG II content that occurred in the rats infused with Val5-ANG II
      alone. These results demonstrate that AT1 receptor blockade markedly reduces the
      intrarenal uptake of circulating ANG II that occurs in ANG II induced
      hypertension.

PMID- 9633794
TI  - Inhibition by (-)-cicletanine of the vascular reactivity to angiotensin II and
      vasopressin in isolated rat vessels.
AB  - In pithed rats, the levorotatory (-)-enantiomer of cicletanine reduces the
      pressor responses to angiotensin II (AII) and also, to a lesser extent, those to
      arginine-vasopressin (AVP). Here we have attempted to characterize further these
      inhibitory effects by studies of isolated perfused rat kidney and mesenteric
      vascular beds. In the isolated rat kidney, (-)-cicletanine behaves as a
      noncompetitive antagonist of AII- and AVP-receptor stimulation, with Ki values of
      9.6 and 208 micromol/L respectively. In the isolated mesenteric vascular bed, (-)
      cicletanine antagonized both AII dependent contractions with an inhibitory
      concentration (IC50) of 54.0 +/- 20.5 micromol/L (n = 6), and AVP dependent
      contractions with an IC50 of 31.6 +/- 5.0 micromol/L (n = 8). In conclusion, (-)
      cicletanine antagonizes AII more effectively in rat kidney than in mesenteric
      vascular beds. Moreover, in rat kidney vascular beds (-)-cicletanine is more
      potent in blocking the pressor responses to AII than in blocking those to AVP. A
      selective blockade of AII induced contractions in kidney vascular beds can be one
      factor explaining both the greater antagonistic potency of (-)-cicletanine
      against AII compared with AVP in pithed rats, and the renal protective properties
      of cicletanine in both hypertensive and aged rats.

PMID- 9633795
TI  - Increased tissue neutral endopeptidase 24.11 activity in spontaneously
      hypertensive hamsters.
AB  - The purpose of this study was to determine whether tissue neutral endopeptidase
      (NEP) 24.11 activity, a membrane-bound metalloenzyme widely distributed in the
      peripheral circulation that cleaves and inactivates vasodilator peptides, is
      increased in spontaneously hypertensive hamsters relative to genetically/age
      matched normotensive hamsters. Mean arterial pressure and heart rate were 163 +/-
      11 mm Hg and 312 +/- 7 beats/min in spontaneously hypertensive hamsters and 99 +/
      3 mm Hg and 302 +/- 10 beats/min in normotensive hamsters, respectively (mean +/
      SEM). NEP 24.11 activity is significantly increased in the kidney, cheek pouch,
      and spinotrapezius muscle, and significantly decreased in the heart and aorta of
      spontaneously hypertensive hamsters relative to controls (P < .05). Lung and
      brain NEP 24.11 activity is similar in both groups. Renal NEP 24.11 activity
      increases and to a similar extent in spontaneously hypertensive and normotensive
      hamsters as chloride anion concentration in the assay buffer is increased.
      Substituting citrate for chloride anion significantly attenuates renal NEP 24.11
      activity. Taken together, these data indicate that NEP 24.11 activity in
      spontaneously hypertensive hamsters is increased in two organs that contribute
      appreciably to peripheral vascular resistance, skeletal muscle, and kidney. We
      suggest that the spontaneously hypertensive hamster is a suitable model to study
      the role of skeletal muscle and renal NEP 24.11 in regulating vasomotor tone in
      essential hypertension.

PMID- 9633796
TI  - Effect of octreotide on 24-h blood pressure profile in acromegaly.
AB  - The aim of the study was to investigate the effect of octreotide, a somatostatin
      analog drug potentially able to inhibit growth hormone (GH), on the circadian
      blood pressure profile in a group of patients with acromegaly. Ten patients with
      GH-secreting pituitary adenoma were studied before and 6 months after treatment
      with subcutaneous octreotide 0.2 to 0.6 mg/day. Twenty-four hour blood pressure
      and heart rate were measured every 15 min at daytime (07:00 to 22:59) and every
      30 min at nighttime (23:00 to 06:59) using a TM-2420 recorder. No correlation was
      found between GH levels and 24-h blood pressure in baseline conditions. Untreated
      patients had a significant nocturnal decrease of both systolic and diastolic
      blood pressure (P < .01), and all showed a circadian systolic or diastolic blood
      pressure rhythm. During octreotide treatment, 24 h as well as nighttime systolic
      and diastolic blood pressures significantly increased (P < .05), whereas daytime
      systolic and diastolic blood pressures did not change. Treated patients did not
      have a nocturnal decline in both systolic and diastolic blood pressures (P = NS),
      and eight lost their systolic or diastolic blood pressure rhythm. In conclusion,
      blood pressure circadian rhythm seems to be maintained in acromegaly. Octreotide
      treatment is associated with an increase of 24-h and nighttime blood pressure,
      and with loss of circadian blood pressure rhythm. Splanchnic vasoconstriction by
      this drug, shifting blood to peripheral vessels, may explain this phenomenon.

PMID- 9633797
TI  - Comparison of effects of antihypertensive drugs on heart rate: changes from
      baseline by baseline group and over time. Department of Veterans Affairs
      Cooperative Study Group on Antihypertensive Agents.
AB  - Baseline heart rate is becoming recognized as a predictor of cardiovascular risk.
      Various antihypertensive drugs have differing effects on heart rate. A randomized
      controlled clinical trial of 1292 ambulatory men with stage 1 or 2 hypertension
      was conducted in 15 Veterans Affairs medical centers. Patients were treated with
      hydrochlorothiazide, atenolol, captopril, clonidine, diltiazem, prazosin, or
      placebo for up to 2 years. Heart rates were measured at baseline, the end of
      titration, 1 year, and 2 years. Data were also stratified by baseline heart rate.
      A subset of patients had heart rate also determined by electrocardiogram. All
      drugs except prazosin reduced heart rate from baseline; additional small
      decreases were obtained over time with hydrochlorothiazide and placebo. The
      decrease initially achieved with clonidine was attenuated over time. The overall
      reduction in heart rate was greatest for atenolol (-12.2 beats/min) and least for
      prazosin (+3.8 beats/min). Only atenolol effected a further reduction of heart
      rate for patients whose baseline rate was < or =65 beats/min. All drugs reduced
      heart rate when the baseline was > or =85 beats/min. Data derived by
      electrocardiogram yielded similar results. The drugs used in this study differ in
      their ability to reduce heart rate, sustain that reduction over time, and to
      change heart rate in groups with high or low rates at baseline. The importance of
      these comparative changes as independent cardiac risk factor variables remains to
      be determined.

PMID- 9633798
TI  - No relevant seasonal influences on office and ambulatory blood pressure: data
      from a study in borderline hypertensive primary care patients.
AB  - Our objective was to study seasonal influences on office and ambulatory blood
      pressure. We therefore designed a prospective 7-month study of 47 borderline
      hypertensive patients in a primary care setting. We used no interventions. Our
      main outcome measures were the differences between summer and winter office and
      ambulatory blood pressures and 95% confidence intervals. Results showed that
      winter minus summer differences ranged from 0 to 3 mm Hg. Only one significant
      difference was found: ambulatory systolic daytime pressure was significantly
      higher (3 mm Hg) in winter than in summer. Our results do not confirm the data of
      earlier studies in hypertensives. In view of the small and clinically irrelevant
      winter-summer differences, it seems unnecessary to modify antihypertensive
      treatment of borderline hypertensives according to the season.

PMID- 9633799
TI  - How reliable is nighttime blood pressure dipping?
AB  - This report examines the reliability of nighttime blood pressure dipping. Twenty
      one individuals were studied twice with ambulatory blood pressure monitoring. On
      one occasion they were studied as outpatients, and on the other as inpatients on
      a clinical research ward. Blood pressure monitoring revealed the expected dip in
      blood pressure at nighttime. However, there was little test-retest reliability
      across the two settings. The test-retest correlations for the dip in blood
      pressure across the two settings were nonsignificant for systolic, diastolic, and
      mean arterial blood pressure. Caution is advised before diagnosing dipping or
      nondipping on the basis of one 24-h ambulatory blood pressure recording.

PMID- 9633800
TI  - Training students in education of the hypertensive patient: enhanced performance
      after a simulated patient instructor (SPI)-based exercise.
AB  - The process whereby a physician explains to the ill patient what has gone wrong
      and what can be done about it can be taught and evaluated by simulated patients
      (SPIs). This study was designed to determine whether a training experience in
      educating a diabetic SPI improves subsequent performance with a hypertensive SPI.
      Competence in educating a hypertensive SPI by students who had no prior training
      experience (n = 26) was compared to that of an experimental group (n = 20) that
      had a prior training session. Performance was assessed with a counseling skills
      scale and a case-specific content checklist (1 = poor to 5 = excellent). Students
      in the experimental group performed better than controls in both counseling
      skills (4.46 v 3.86, P < .01) and completeness of coverage of content (3.28 v
      2.65, P < .01). Students in both groups focused more on clinical features and
      treatment than on laboratory testing and follow-up. The ability to counsel
      "patients" with hypertension can be enhanced by a prior learning experience with
      a diabetic SPI. Clinical application of knowledge about hypertension can be
      assessed by SPIs.

PMID- 9633801
TI  - Hemodynamic differences between metoprolol and carvedilol in hypertensive
      patients.
AB  - Resting hemodynamics were measured before, at 2 and 24 h after the first dose,
      and after 4 weeks of monotherapy with either metoprolol or carvedilol in a
      randomized single-blind study. We analyzed results from 24 hypertensive patients
      (30-68 years of age) with adequate blood-pressure lowering on monotherapy.
      Acutely, both drugs lowered systolic blood pressure and heart rate. Whereas
      metoprolol reduced cardiac output and increased both systemic and femoral artery
      resistance, carvedilol did not alter cardiac output but led to reductions in the
      systemic and regional resistances. After 4 weeks of therapy, cardiac output
      remained reduced and vascular resistances increased in the metoprolol group,
      whereas in carvedilol patients cardiac output continued to be unchanged and the
      trend for vascular resistances to be decreased persisted. Acutely and chronically
      the differences in the hemodynamic effects of the two medications were
      statistically significant. The study results indicate that carvedilol's
      vasodilatory action is not subject to tolerance development. Chronic afterload
      reduction associated with the decrease in systemic vascular resistance may lead
      to additional savings in myocardial oxygen consumption, a beneficial feature
      particularly in those patients with concomitant ischemic heart disease. It may
      also have a favorable influence on concentric cardiac hypertrophy and changes in
      the walls of arteriolar resistance vessels.

PMID- 9633802
TI  - Cost-minimization and the number needed to treat in uncomplicated hypertension.
AB  - The goal of this study was to compare the direct costs associated with the
      prescription of thiazide diuretics, beta-receptor blockers (beta-blockers),
      angiotensin converting enzyme inhibitors (ACEI), a-receptor blockers (alpha
      blockers), and calcium channel blockers (CCB) for the prevention of stroke,
      myocardial infarction (MI) and premature death in uncomplicated hypertension. We
      performed a cost-minimization analysis based on numbers-needed-to-treat (NNT)
      derived from the metaanalysis of 15 major clinical trials of hypertension
      treatment, and the average wholesale prices of both the most commonly prescribed
      and the least expensive drugs in each class. The inclusion criteria for clinical
      trials were that they be randomized, controlled trials of drug therapy of
      uncomplicated mild-to-moderate hypertension with stroke, MI, or death as
      endpoints. The wholesale drug costs and the total direct outpatient treatment
      costs to prevent a stroke, MI or death among middle-aged and elderly
      hypertensives were our outcome measures. The estimated wholesale drug acquisition
      cost to prevent one major event (MI or stroke or death) ranged from $4730 to
      $346,236 among middle-aged patients, and from $1595 to $116,754 in the elderly;
      generic diuretic or beta-blocker therapy was more economical than treatment with
      an ACEI, alpha-blocker, or CCB. The associated 5-year NNT was 86 for middle-aged
      patients and 29 for elderly patients. Diuretic therapy remained more cost
      effective even under the unlikely assumption that the newer drugs were 50% more
      effective than diuretics at preventing these major events. The costs associated
      with potassium supplementation did not eliminate the advantage of diuretics.
      Treatment costs to prevent major hypertensive complications are much lower with
      diuretics and beta-blockers than with ACEI, CCB, or alpha-blockers, especially in
      middle-aged patients.

PMID- 9633803
TI  - Differential effects of central and peripheral nerves on macrophages and
      microglia.
AB  - The poor ability of injured central nervous system (CNS) axons to regenerate has
      been correlated, at least partially, with a limited and suppressed postinjury
      inflammatory response. A key cell type in the inflammatory process is the
      macrophage, which can respond in various ways, depending on the conditions of
      stimulation. The aim of this study is to compare the activities of macrophages or
      microglia when encountering CNS and peripheral nervous systems (PNS), on the
      assumption that nerve-related differences in the inflammatory response may have
      implications for tissue repair and thus for nerve regeneration. Phagocytic
      activity of macrophages or of isolated brain-derived microglia was enhanced upon
      their exposure to sciatic (PNS) nerve segments, but inhibited by exposure to
      optic (CNS) nerve segments. Similarly, nitric oxide production by macrophages or
      microglia was induced by sciatic nerve segments but not by optic nerve segments.
      The previously demonstrated presence of a resident inhibitory activity in CNS
      nerve, could account, at least in part, for the inhibited phagocytic activity of
      blood-borne macrophages in CNS nerve as well as of microglia resident in the
      brain. It seems that the CNS microglia are reversibly immunosuppressed by the CNS
      environment, at least with respect to the activities examined here. It also
      appears from this study that the weak induction of early healing-related
      activities of macrophages/microglia in the environment of CNS might explain the
      subsequent failure of this environment to acquire growth-supportive properties in
      temporal and spatial synchrony with the needs of regrowing axons.

PMID- 9633804
TI  - Visualization of mitotic radial glial lineage cells in the developing rat brain
      by Cdc2 kinase-phosphorylated vimentin.
AB  - Although accumulating data reveal patterns of proliferation, migration, and
      differentiation of neuronal lineage cells in the developing brain, gliogenesis in
      the brain has not been well elucidated. In the rat brain, vimentin is selectively
      expressed in radial glia and in their progeny, not in oligodendrocytes or neurons
      from embryonic day 15 (E15) until postnatal day 15 (P15). Here we examined
      mitotic radial glial lineage cells in the rat brain E17-P7, using the monoclonal
      antibody 4A4, which recognizes vimentin phosphorylated by a mitosis-specific
      kinase, cdc2 kinase. In the neocortex, mainly radial glia in the ventricular
      zone, but not their progeny, underwent cell division. In contrast, not only
      radial glia but also various types of radial glial progeny including Bergmann
      glia continued to proliferate in the cerebellum. Radial glia in the neocortex
      divided horizontally, obliquely, and vertically against the ventricular surface.
      The percentage of the vertical division increased with progress in the stage of
      development, concurrently with the decrease of the population of horizontal
      divisions. Thus, the monoclonal antibody 4A4 provides an useful tool to label
      mitotic glia in the developing brain and revealed different patterns of
      gliogenesis in the neocortex and cerebellum. A possibility is discussed that the
      dynamics of mitotic orientation observed here may be related to the change of the
      pattern of gliogenesis during development.

PMID- 9633805
TI  - Glial cells have heart: rH1 Na+ channel mRNA and protein in spinal cord
      astrocytes.
AB  - Astrocytes in vitro express several distinct voltage-sensitive sodium currents,
      including tetrodotoxin (TTX)-resistant in non-stellate astrocytes and TTX
      sensitive currents in stellate astrocytes. However, the molecular identity of the
      underlying channels, and the mechanisms that regulate their expression, have yet
      to be identified. Since spinal cord astrocytes in vitro express sodium currents
      that are nearly ten-fold greater that those of astrocytes derived from other
      regions, we used reverse transcription polymerase chain reaction (RT-PCR), in
      situ hybridization, and immunocytochemistry to search for a sodium channel mRNA
      and protein corresponding to a TTX-resistant channel in these cells. RT-PCR did
      not detect transcripts for SNS, which is known to encode a TTX-resistant current
      in dorsal root ganglion neurons. However, RT-PCR demonstrated the presence of rH1
      mRNA in cultured spinal cord astrocytes derived from postnatal day 0 (P0) Sprague
      Dawley rats at 7 days in vitro and in also intact spinal cords of P0 and P7 rats.
      Hybridization signal for rH1 mRNA was detected by in situ hybridization
      cytochemistry in most non-stellate and, at varying levels, in stellate astrocytes
      in these cultures. Immunocytochemical studies, utilizing a polyclonal antibody (R
      12) generated against a conserved polypeptide sequence of sodium channels,
      demonstrated sodium channel immunoreactivity in non-stellate and stellate
      astrocytes in these cultures. Spinal cord cultures reacted with a rH1-specific
      polyclonal antibody also showed rH1 immunostaining in non-stellate and stellate
      astrocytes, although the intensity of the rH1 immunoreactivity in both astrocyte
      morphologies was attenuated compared to that observed with the R-12 generic
      sodium channel antibody. The presence of rH1 mRNA and protein in non-stellate
      astrocytes in vitro provides a possible correlate for the TTX-resistant current
      that has been recorded in these cells. Since TTX-resistant current is not present
      in stellate astrocytes, the presence of rH1 mRNA and protein in these cells
      suggests, in addition, that post-translational mechanisms participate in the
      control of sodium channel expression in these cells.

PMID- 9633806
TI  - Spermine/spermidine is expressed by retinal glial (Muller) cells and controls
      distinct K+ channels of their membrane.
AB  - There is recent evidence that polyamines such as spermine (spm) and spermidine
      (spd) may act as endogenous modulators of the activity of inwardly rectifying K+
      channels. This type of K+ channels is abundantly expressed by retinal glial
      (Muller) cells where they are involved in important glial cell functions such as
      the clearance of excess extracellular K+ ions. This prompted us to study the
      following questions, i) do mammalian Muller cells contain endogenous spm/spd?;
      ii) do Muller cells possess the enzymes (e.g., ornithine decarboxylase, ODC)
      necessary to produce spm/spd?; and iii) does application of exogenous spm/spd
      exert specific effects onto inwardly rectifying K+ channels of Muller cells?
      Immunocytochemical studies were performed on histological sections of guinea-pig,
      rabbit, porcine, and human retinae, and on enzymatically dissociated Muller
      cells. Whole-cell and patch-clamp recordings were performed on enzymatically
      dissociated porcine and guinea-pig Muller cells. All above-mentioned questions
      could be answered with "yes." Specifically, the majority of Muller cells were
      labeled with antibodies directed to spm/spd, both within retinal sections and
      enzymatically isolated from retinal tissue. Muller cells in normal retinae
      express low levels of ODC but increase this expression markedly in cases of
      retinal pathology such as experimental epiretinal melanoma. Externally applied
      polyamines (1 mM) reduce (predominantly inward) whole-cell K+ currents, with the
      efficacies being spm > spd > put. If applied at the inside of membrane patches,
      spm (1 mM) blocks completely the outward currents through inwardly rectifying K+
      channels but fails to affect the activity of large conductance, Ca2+-activated K+
      channels. It is concluded that Muller cells contain endogenous channel-active
      polyamines, the synthesis of which may be up-regulated in pathological
      situations, and which may be involved in the control of both glial function and
      cell proliferation.

PMID- 9633807
TI  - Glial cell responses, complement, and clusterin in the central nervous system
      following dorsal root transection.
AB  - We have examined the glial cell response, the possible expression of compounds
      associated with the complement cascade, including the putative complement
      inhibitor clusterin, and their cellular association during Wallerian degeneration
      in the central nervous system. Examination of the proliferation pattern revealed
      an overall greater mitotic activity after rhizotomy, an exclusive involvement of
      microglia in this proliferation after peripheral nerve injury, but, in addition,
      a small fraction of proliferating astrocytes after rhizotomy. Immunostaining with
      the phagocytic cell marker ED1 gradually became very prominent after rhizotomy,
      possibly reflecting a response to the extensive nerve fiber disintegration.
      Lumbar dorsal rhizotomy did not induce endogenous immunoglobulin G (IgG)
      deposition or complement expression in the spinal cord dorsal horn, dorsal
      funiculus, or gracile nucleus. This is in marked contrast to the situation after
      peripheral nerve injury, which appears to activate the entire complement cascade
      in the vicinity of the central sensory processes. Clusterin, a multifunctional
      protein with complement inhibitory effects, was markedly upregulated in the
      dorsal funiculus in astrocytes. In addition, there was an intense induction of
      clusterin expression in the degenerating white matter in oligodendrocytes,
      possibly reflecting a degeneration process in these cells. The findings suggest
      that 1) complement expression by microglial cells is intimately associated with
      IgG deposition; 2) axotomized neuronal perikarya, but not degenerating central
      fibers, undergo changes which induce such deposition; and 3) clusterin is not
      related to complement expression following neuronal injury but participates in
      regulating the state of oligodendrocytes during Wallerian degeneration.

PMID- 9633808
TI  - Lesion-induced changes in the expression of ciliary neurotrophic factor and its
      receptor in rat optic nerve.
AB  - There is evidence that ciliary neurotrophic factor (CNTF) is involved in reactive
      changes following lesions of the nervous system. To investigate, whether
      differences in the regulation of CNTF and CNTF receptor alpha (CNTFRalpha)
      contribute to the differences in PNS and CNS responses to injury, we have studied
      their expression on the mRNA and protein level in the rat optic nerve following a
      crush lesion to compare them with the situation in peripheral nerve. Seven days
      after the lesion, CNTF mRNA and protein levels were markedly decreased at the
      lesion site, concommitant with the disappearance of GFAP- and CNTF-immunopositive
      astrocytes. CNTF levels in proximal and distal parts were less affected. This was
      in contrast to the situation in the PNS, where CNTF was downregulated at and
      distal to the lesion site. Different from other CNS regions, optic nerve
      astrocytes expressed CNTFRalpha mRNA under normal conditions. Following lesion,
      CNTFRalpha was reduced substantially only in distal and proximal parts of the
      optic nerve but continued to be expressed at high levels at the lesion site,
      suggesting that GFAP-negative, CNTF-responsive cells are present there. Our
      results suggest that differences in lesion-induced changes in the optic and
      sciatic nerve reflect differences in the response to injury of astrocytes and
      Schwann cells. In the light of the known actions of CNTF in inducing
      astrogliosis, the expression pattern observed in the optic nerve indicates that
      CNTF and CNTFRalpha are involved in glial scar formation in the lesion area.

PMID- 9633809
TI  - Relationship of microglial and astrocytic activation to disease onset and
      progression in a transgenic model of familial ALS.
AB  - Transgenic mice that highly over-express a mutated human CuZn superoxide
      dismutase (SOD1) gene [gly93-->ala; TgN(SOD1-G93A)G1H line] found in some
      patients with familial ALS (FALS) have been shown to develop motor neuron disease
      that is characterized by motor neuron loss in the lumbar and cervical spinal
      regions and a progressive loss of motor activity. The mutant Cu,Zn SOD exhibits
      essentially normal SOD activity but also generates toxic oxygen radicals as a
      result of an enhancement of a normally minor peroxidase reaction. Consequently,
      lipid and protein oxidative damage to the spinal motor neurons occurs and is
      associated with disease onset and progression. In the present study, we
      investigated the time course of microglial (major histocompatibility-II antigen
      immunoreactivity) and astrocytic (glial fibrillary acidic protein
      immunoreactivity) activation in relation to the course of motor neuron disease in
      the TgN(SOD1-G93A)G1H FALS mice. Four ages were investigated: 30 days (pre-motor
      neuron pathology and clinical disease); 60 days (after initiation of pathology,
      but pre-disease); 100 days (approximately 50% loss of motor neurons and
      function); and 120 days (near complete hindlimb paralysis). Compared to non
      transgenic littermates, the TgN(SOD1-G93A)G1H mice showed significantly increased
      numbers of activated astrocytes (P < 0.01) at 100 days of age in both the
      cervical and lumbar spinal cord regions. However, at 120 days of age, the
      activation lost statistical significance. In contrast, microglial activation was
      significantly increased several-fold at both 100 and 120 days. We hypothesize
      that astrocytic activation may exert a trophic influence on the motor neurons
      that is insufficiently maintained late in the course of the disease. On the other
      hand, the sustained, intense microglial activation may conceivably contribute to
      the oxidative stress and damage involved in the disease process. If true, then
      agents which inhibit microglia may help to limit disease progression.

PMID- 9633810
TI  - E587 antigen is upregulated by goldfish oligodendrocytes after optic nerve lesion
      and supports retinal axon regeneration.
AB  - The properties of glial cells in lesioned nerves contribute quite substantially
      to success or failure of axon regeneration in the CNS. Goldfish retinal axons
      regenerate after optic nerve lesion (ONS) and express the L1-like cell adhesion
      protein E587 antigen on their surfaces. Goldfish oligodendrocytes in vitro also
      produce E587 antigen and promote growth of both fish and rat retinal axons. To
      determine whether glial cells in vivo synthesize E587 antigen, in situ
      hybridizations with E587 antisense cRNA probes and light- and electron
      microscopic E587 immunostainings were carried out. After lesion, the goldfish
      optic nerve/tract contained glial cells expressing E587 mRNA, which were few in
      number at 6 days after ONS, increased over the following week and declined in
      number thereafter. Also, E587-immunopositive elongated cells with ultrastructural
      characteristics of oligodendrocytes were found. Thus, glial cells synthesize E587
      antigen in spatiotemporal correlation with retinal axon regeneration. To
      determine the functional contribution of E587 antigen, axon-oligodendrocyte
      interactions were monitored in co-culture assays in the presence of Fab fragments
      of a polyclonal E587 antiserum. E587 Fabs in axon-glia co-cultures prevented the
      normal tight adhesion of goldfish retinal growth cones to oligodendrocytes and
      blocked the preferential growth of fish and rat retinal axons on the
      oligodendrocyte surfaces. The ability of glia in the goldfish visual pathway to
      upregulate the expression of E587 antigen and the growth supportive effect of
      oligodendrocyte-associated E587 antigen in vitro suggests that this L1-like
      adhesion protein promotes retinal axon regeneration in the goldfish CNS.

PMID- 9633811
TI  - [U-13C] aspartate metabolism in cultured cortical astrocytes and cerebellar
      granule neurons studied by NMR spectroscopy.
AB  - The metabolism of [U-13C]aspartate was studied in cultured cortical astrocytes
      and cerebellar granule neurons in the presence of glucose and during inhibition
      of glycolysis. Redissolved, lyophilized cell extracts and incubation media were
      analyzed by 13C nuclear magnetic resonance spectroscopy for the determination of
      metabolites labeled from aspartate. Uniformly labeled lactate was prominent in
      control media of astrocytes and cerebellar granule neurons. In both cell types,
      aspartate entered the tricarboxylic acid (TCA) cycle, as shown by labeling
      patterns in glutamate and, in astrocytes, in glutamine. From the complex labeling
      patterns in aspartate in astrocytic perchloric acid extracts it was clear that
      acetylcoenzyme A (acetyl-CoA) derived from aspartate via oxaloacetate and
      pyruvate could enter the TCA cycle. Such "recycling," however, could not be
      detected in cerebellar granule neurons. Inhibition of glycolysis reduced
      aspartate uptake and metabolism in both cell types. Most notably, lactate derived
      from aspartate showed a large reduction, and in astrocytes, incorporation of
      labeled acetyl-CoA into the TCA cycle was significantly reduced. Thus, astrocytes
      and cerebellar granule neurons differ in their handling of aspartate.
      Furthermore, inhibition of glycolysis clearly affected aspartate metabolism by
      such cells.

PMID- 9633812
TI  - Oligodendroglial reaction following spinal cord injury in rat: transient
      upregulation of MBP mRNA.
AB  - The reaction of oligodendrocytes in response to traumatic injury of the CNS are
      poorly understood. In the present report we studied changes in the expression of
      a major constituent of CNS myelin, myelin basic protein (MBP), by
      immunohistochemistry and in situ hybridization from 6 h up to 2 weeks following
      partial transection of the spinal cord in adult rats. MBP immunohistochemistry
      showed degeneration of myelin at the lesion center and signs of myelin breakdown
      in necrotic foci in the dorsal and ventral funiculi proximal and distal to the
      lesion. In situ hybridization revealed that mRNA for MBP was downregulated at the
      local lesion site within the first day following injury, probably reflecting
      oligodendrocytes to undergo cell death. From 2 days on, however, MBP mRNA was
      conspicuously upregulated at the border of the lesion area. This "reactive"
      response of surviving oligodendrocytes, as indicated by increased levels of MBP
      mRNA, peaked around 8 days. At this time, oligodendrocytes displaying strong MBP
      in situ signal formed stripe-like structures which were oriented radially toward
      the lesion center and arranged in parallel to neurofilament-positive axons. At
      around 2 weeks post-injury, MBP mRNA at the border of the lesion area was again
      downregulated to levels comparable to uninjured controls. These results show that
      traumatic injury of the spinal cord induces a "reactive" response of surviving
      oligodendrocytes adjacent to lesion sites. This response might represent an
      important component of local repair mechanisms.

PMID- 9633813
TI  - Proof of "disease causing" mutation.

PMID- 9633814
TI  - Pooled analysis of p53 mutations in hematological malignancies.
AB  - A computerized database is described that contains information about 507
      mutations in the p53 gene of hematologic tumors and corresponding cell lines.
      Analysis of these mutations indicated the following findings: First, mutational
      spectrum analysis in these tumors was found to be similar to the pattern found
      for other solid tumors. However, when the patterns of base substitutions were
      examined separately according to the types of hematologic malignancies, followed
      by subgroup analysis, notable differences (in some cases of statistical
      significance) emerged. Second, mutational pattern analysis indicates that about
      48% of base substitutions in hematologic tumors are suspected to be associated
      with carcinogen exposure. Third, deletions and insertions are localized mainly to
      exons 5-8 and repeated DNA sequences. However, the unusual profile of variations
      in frequency within each type of tumor suggests that, in addition to endogenous
      damage to template DNA, there is the factor of exposure to environmental physical
      and chemical carcinogens/mutagens. Fourth, p53 protein alterations analysis
      indicate that most of the changes in the amino acids are "semiconservative,"
      presumably in order to avoid disrupting the structure of the p53 monomer.
      Consistent with this notion, structural mutations are more conservative than the
      binding mutations. Finally, molecular mechanisms that lead to p53 mutations,
      etiological factors that play a role in their formation, and the
      pathophysiological significance of consequent p53 protein alterations are
      discussed.

PMID- 9633815
TI  - Spectrum of mutations in the fumarylacetoacetate hydrolase gene of tyrosinemia
      type 1 patients in northwestern Europe and Mediterranean countries.
AB  - Hereditary tyrosinemia type 1 (HT1) is a rare metabolic disease caused by a
      deficient activity of the enzyme fumarylacetoacetase (FAH). To investigate the
      molecular heterogeneity of tyrosinemia, the geographic distribution and the
      genotype-phenotype relationship, we have analyzed the FAH genotype of 25 HT1
      patients. Mutation screening was performed by PCR amplification of exons 1-14 of
      the FAH gene, followed by SSCP analysis and direct sequencing of the amplified
      exons. Fourteen different mutations were found, of which seven were novel, viz.
      three missense mutations (G158D, P261L, F405H), a deletion of three nucleotides
      causing a deletion of serine (DEL366S) and three splice site mutations: IVS2+1(g
      t), IVS6-1(g-c), IVS8-1(g-c). The splice site mutations IVS6-1(g-t) and IVS12+5(g
      a) were frequently found in countries around the Mediterranean and northwestern
      Europe, respectively. No clear correlation between the genotype and the three
      major HT1 subtypes could be established.

PMID- 9633816
TI  - Molecular diagnosis of McArdle disease: revised genomic structure of the
      myophosphorylase gene and identification of a novel mutation.
AB  - McArdle disease is a rare autosomal recessive disorder of the muscle glycogen
      metabolism caused by mutations in the muscle glycogen phosphorylase gene. Until
      now, a total number of 11 different mutations in the coding region or splice
      sites of the myophosphorylase gene have been identified. In contrast to a wealth
      of data on the RNA and protein level, little information is available on the
      genomic sequence of the corresponding gene. To facilitate molecular diagnosis of
      McArdle disease, we reinvestigated the genomic structure of the myophosphorylase
      gene and sequenced about 9.8 kilobases (kb) on the genomic level. By choosing 14
      intronic primer pairs, we were able to amplify the complete human coding sequence
      as well as the adjacent splice sites of the 20 exons. Direct sequencing of the
      amplification products of a consanguineous Turkish family with typical McArdle
      disease revealed a novel single base pair deletion in exon 18, which predicts a
      frameshift and a premature termination of the protein. In summary, we established
      a system for molecular diagnosis of McArdle disease based on a revised genomic
      structure of the myophosphorylase gene and demonstrated its feasibility by
      identification of a novel mutation.

PMID- 9633817
TI  - Deletion analysis of Bulgarian SMA families.
AB  - All three types of autosomal recessive spinal muscular atrophy map to chromosome
      region 5q13. Recent reports suggest that they are associated with deletions of
      two adjacent genes: SMN and NAIP. Here we report the first deletion analysis of
      Bulgarian SMA families. Homozygous deletion of exons 7 and 8 of the SMN gene were
      found in 85% of our patients, but the NAIP gene (exons 5 and 6) was deleted in
      only 26% of patients. To our knowledge, these frequencies are some of the lowest
      reported so far. The NAIP gene was deleted predominantly in severely affected
      patients (type I), while in the group with milder types SMA only deletions of the
      SMN gene were detected. Our phenotype-genotype correlation study confirmed that
      larger deletions are associated with more severe clinical course. The Bulgarian
      data support the thesis that the telomeric SMN gene could play a major role in
      determining SMA, while the NAIP or the centromeric SMN copy have a modifying
      effect on the phenotype.

PMID- 9633818
TI  - Mutations of the cationic trypsinogen in hereditary pancreatitis.
AB  - Hereditary pancreatitis (OMIM 167800) is thought to be associated with a mutation
      of the exon 3 of cationic trypsinogen (Nature Genet (1996): 14:141-145). This
      paper reports sequence data of two independent families suffering from this
      disease. PCR amplificates from leukocyte or buccal swab DNA showed no mutation of
      exon 3 of cationic trypsinogen. Instead, in exon 2, an A-to-T tranversion was
      found that led to the substitution of Asn by Ile in the sixth amino acid of the
      active trypsin. In exons 4 and 5, silent mutations were found. In the other
      expressed trypsinogens, several homozygous alterations not associated to
      hereditary pancreatitis were identified. As a model of pathogenesis, we
      hypothesize that mutation of trypsinogen in exon 2 could lead to premature
      cleavage of the activation peptide of trypsinogen or to altered intracellular
      transport.

PMID- 9633819
TI  - Different missense mutations in histidine-108 of lysosomal acid lipase cause
      cholesteryl ester storage disease in unrelated compound heterozygous and
      hemizygous individuals.
AB  - Cholesteryl ester storage disease (CESD) and Wolman disease (WD) are both
      autosomal recessive disorders associated with reduced activity of lysosomal acid
      lipase (LAL), that leads to the tissue accumulation of cholesteryl esters in
      endosomes and lysosomes. WD is caused by genetic defects of LAL that leave no
      residual enzymatic activity, while in CESD patients a residual LAL activity can
      be identified. We have analyzed the LAL cDNA in three CESD patients from two
      nonrelated families and identified the mutations responsible for the disease. The
      associated genetic defects characterized revealed compound heterozygosity for a
      splice defect leading to skipping of exon 8, due to a G-->A transition at
      position -1 of the exon 8 splice donor site, and a point mutation leading to a
      Hisl08Pro change (CAT-->CCT) in two patients (siblings) with mild CESD phenotype.
      A further CESD patient was hemizygous for a His108-->Arg missense mutation (CAT-
      >CGT) in combination with a partial deletion of the LAL gene and was affected
      more severely. Expression of the LAL enzymes with the His108-->Pro and His108-
      >Arg mutation in insect cells revealed residual enzymatic activities of 4.6%
      versus 2.7%, respectively, compared with controls. Therefore, His108 seems to
      play a crucial role in folding or catalytic activity of the lysosomal acid
      lipase. This is the first description of two different, naturally occurring
      mutations involving the same amino acid residue in the lysosomal acid lipase in
      unrelated CESD patients. Moreover, our results demonstrate that the variable
      manifestation of CESD can be explained by mutation-dependent, variable
      inactivation of the LAL enzyme.

PMID- 9633820
TI  - Level of heteroplasmy for the mitochondrial mutation A3243G correlates with age
      at onset of diabetes and deafness.
AB  - The mitochondrial mutation A3243G has been shown to be associated with a syndrome
      of diabetes mellitus and sensorineural hearing loss. Using a solid-phase-based
      sequencing method we have investigated the relation between the proportion of
      mutant mitochondrial genomes and the time of disease onset among members of three
      families where the mutation segregates. A striking association was observed
      between the level of heteroplasmy and time of onset of disease, particularly
      hearing loss. Accordingly, this syndrome shares features of diseases caused by
      dynamic mutations in that variable transmission of the level of heteroplasmy
      between generations influences disease severity.

PMID- 9633821
TI  - Spectrum of mutations in Finnish patients with Charcot-Marie-Tooth disease and
      related neuropathies.
AB  - Our patient material included families and sporadic patients of Finnish origin
      with the diagnosis of Charcot-Marie-Tooth (CMT) disease types 1 and 2, Dejerine
      Sottas syndrome (DSS), and hereditary neuropathy with liability to pressure
      palsies (HNPP). We screened for mutations in the peripheral myelin protein genes
      connexin 32 (Cx32), myelin protein zero (P0) and peripheral myelin protein 22
      (PMP22) by direct sequencing. All patients chosen for mutation screening were
      negative for the 1.5 Mb duplication/deletion at 17p11.2-p12. Eleven Cx32
      mutations were found in 12 families, six with a CMT2 diagnosis, three with a CMT1
      diagnosis and three with unclassified CMT. The total number of patients in these
      12 CMTX families was 61, giving a minimum prevalence of 1.2/100,000 for CMTX in
      Finland. Four of the mutations, Pro58Arg, Pro172Leu, Asn175Asp and Leu204Phe,
      have not been previously reported. One male patient with an early onset CMT had a
      double Cx32 mutation, Arg22Gln and Val63Ile. The double de novo mutation was
      found to be of maternal grandpaternal origin. In the P0 gene a Ser78Leu mutation
      was found in one family with severe CMT1 and a de novo Tyr82Cys mutation was
      found in one DSS patient. Both mutations have been previously reported in other
      CMT1 families. A novel PMP22 mutation, deletion of Phe84, was found in one
      sporadic DSS patient. Our mutation screening results show the necessity of
      molecular diagnosis, in addition to clinical and electrophysiological evaluation,
      for proper subtyping of the disease and for accurate genetic counseling.

PMID- 9633823
TI  - Calcium mediated proteolysis enhances calcium release in skinned L6 myotubes.
AB  - The mechanism for calcium (Ca2+) release in heart and skeletal muscle during
      excitation-contraction coupling is currently unknown. A widely held hypothesis is
      that a small amount of Ca2+ enters the cell and elicits a larger intracellular
      release of Ca2+ from the sarcoplasmic reticulum (SR), termed "Ca2+-induced Ca2+
      release" (CICR). In addition to its role in excitation-contraction coupling, Ca2+
      is also known to activate the cysteine protease calpain, which has been recently
      found to specifically cleave the ryanodine receptor in vitro. The authors
      investigated the question of whether Ca2+ sensitive protease activation could
      account for an apparent CICR. The authors first reproduced the phenomenon of CICR
      using detergent treated L6 myotubes ("skinned cells"). Leupeptin, a cysteine
      protease inhibitor, reduced the initial velocity and extent of Ca2+ release from
      the SR; a similar result was obtained when skinned cells were treated with
      iodoacetate, a sulfhydryl alkylating agent. Dithiothreitol enhanced both the rate
      and extent of Ca2+ release. Caffeine-induced Ca2+-release was unaffected by the
      thiol protease inhibitors or activators. This suggests that a cysteine protease
      may be responsible, in part, for CICR in vitro. The authors also found that
      vesicles exposed to Ca2+ to induce CICR were unable to fully reaccumulate Ca2+ a
      second time. Yet, when caffeine released comparable amounts of Ca2+, the initial
      Ca2+ level was fully restored. Similarly, leupeptin protected the vesicles from
      the reaccumulation deficit induced by Ca2+. The authors' findings suggest that
      proteolysis activated by a Ca2+-sensitive protease may account for the direct in
      vitro demonstration of CICR; such an effect may more likely reflect a role in
      apoptosis than excitation-contraction coupling.

PMID- 9633822
TI  - Fibroblast growth factor-2 and TPA enhance prostate-cancer-cell proliferation and
      activate members of the Ras and PKC signal transduction pathways.
AB  - Rat prostate-cancer-cell stable-transfectants expressing either antisense
      fibroblast growth factor (FGF-1) or antisense-FGF-2 transcripts that respectively
      have either undetectable FGF-1 or profoundly diminished FGF-2 protein content,
      were used for analyses of FGF-2 and/or 12-O-tetradecanoylphorbol 12-acetate (TPA)
      modulation of cell proliferation. Antisense-FGF-2 transfectant doubling-time was
      2.6-fold greater than that of vector-control transfectants. FGF-2 and TPA
      respectively caused 2.5- and 3.0-fold reductions in antisense-FGF-2 transfectant
      doubling-time. Culture of antisense-FGF-2 transfectants in medium containing both
      FGF-2 and TPA further reduced their doubling time; however, this effect was not
      statistically different from that achieved by TPA treatment alone. Antisense-FGF
      1 transfectant doubling-time was 2.2-fold greater than that of vector-control
      transfectants and was reduced 2.0- or 2.3-fold, respectively, when these cells
      were cultured in medium containing FGF-2 or TPA. In contrast to the results for
      antisense-FGF-2 transfectants, culture of antisense-FGF-1 transfectants in medium
      containing both FGF-2 and TPA caused a 2.6-fold reduction in transfectant
      doubling-time that was significantly greater than that caused by independent
      treatment with either FGF-2 or TPA. FGF-2 promoted rapid activation of rat
      prostate-cancer-cell PKCalpha and PKCepsilon, as assessed by isozyme
      translocation from the soluble to particulate cell fraction, and only moderately
      altered PKCdelta distribution. By contrast, TPA promoted rapid activation of all
      three PKC isozymes. Both the TPA- and FGF-2-mediated PKC activation were
      prolonged and possibly involved cyclic redistribution of isozymes between soluble
      and particulate cell fractions. FGF-2 also caused rapid phosphorylation of
      prostate-cancer-cell Shc, the adapter protein that mediates FGF-receptor
      modulated ras signaling. The results of these studies indicate that FGF-2 and TPA
      independently and conjointly modulate rat prostate-cancer-cell antisense
      transfectant doubling time and suggest that effector modulation of rat prostate
      cancer-cell proliferation is achieved by processes involving PKC and/or ras
      mediated signaling.

PMID- 9633824
TI  - IGF-I receptor protection from apoptosis in cells lacking the IRS proteins.
AB  - The type I insulin-like growth factor receptor (IGF-IR) plays a crucial role in
      cell growth, transformation and protection from apoptosis. Although the mitogenic
      function of the IGF-IR may require the activation of insulin receptor substrate-1
      (IRS-1) or IRS-2, an overexpressed IGF-IR is able to protect 32D cells, which
      lack IRS-1 and IRS-2, from apoptosis caused by Interleukin-3 (IL-3) withdrawal.
      Here, using mutational analysis, the authors identify domains of the IGF-IR
      necessary to protect from apoptosis without downstream signaling from IRS-1 and
      IRS-2. A receptor mutant of the tyrosine kinase (TK) domain only partially
      inhibited antiapoptotic signaling, whereas a mutant displaying constitutive
      autophosphorylation of the receptor did not show enhanced survival activity.
      Surprisingly, survival signaling was dependent upon tyrosine 950, the binding
      site for IRS-1, IRS-2, and Shc proteins. Yet, overexpressed Shc and/or IRS-1
      could not replace the IGF-IR survival signal, suggesting the existence of other
      critical substrates. Finally, the C-terminus may encode a proapoptotic signal, as
      receptors truncated at C-terminal residues 1229 or 1245 were found to inhibit
      apoptosis better than the wild type (WT) IGF-IR.

PMID- 9633825
TI  - Multiple phosphotyrosine phosphatase mRNAs are expressed in the human lung
      fibroblast cell line WI-38.
AB  - Protein tyrosine phosphatases are important components of signal transduction
      pathways. The authors have used reverse transcription/polymerase chain reactions
      to accomplish a comprehensive examination of the RNA expression for 58 distinct
      mammalian protein tyrosine and dual specificity phosphatase (PTPase) and PTPase
      like genes in the normal human diploid fibroblast cell line WI-38. Thirty-seven
      of these PTPase genes express easily measurable RNA, and four simultaneously
      express the RNA for two or more isoforms. Messages for an additional eight PTPase
      genes are detectable at low levels. Only 14 known PTPase genes do not express
      measurable RNA under our conditions. For purposes of comparison, the authors also
      assessed the PTPases expressed in the WI-38 cell line using highly degenerate
      primers to conserved motifs found in the classical tyrosine-specific PTPases.
      Only eight of the 22 classic tyrosine-specific PTPases detected using the
      specific primers were detected using these degenerate primers. Our panel of
      specific PTPase primers should be very useful for semiquantitatively assessing
      the repertoire of PTPases expressed by cells.

PMID- 9633826
TI  - Limited proteolysis for assaying ligand binding affinities of nuclear receptors.
AB  - The binding of natural or synthetic ligands to nuclear receptors is the
      triggering event leading to gene transcription activation or repression. Ligand
      binding to the ligand binding domain of these receptors induces conformational
      changes that are evidenced by an increased resistance of this domain to
      proteases. In vitro labeled receptors were incubated with various synthetic or
      natural agonists or antagonists and submitted to trypsin digestion. Proteolysis
      products were separated by SDS-PAGE and quantified. The amount of trypsin
      resistant fragments was proportional to receptor occupancy by the ligand, and
      allowed the determination of dissociation constants (kDa). Using the wild-type or
      mutated human retinoic acid receptor alpha as a model, kDa values determined by
      classical competition binding assays using tritiated ligands are in agreement
      with those measured by the proteolytic assay. This method was successfully
      extended to human retinoic X receptor alpha, glucocorticoid receptor, and
      progesterone receptor, thus providing a basis for a new, faster assay to
      determine simultaneously the affinity and conformation of receptors when bound to
      a given ligand.

PMID- 9633827
TI  - Endothelin-induced calcium signaling and secretion in chief cells and fibroblasts
      from pathological human parathyroid glands.
AB  - Endothelins (ETs) are 21 amino acid peptides with vasoactive and mitogenic
      properties. The three isopeptides (ET-1, -2, and -3) and their receptors (E1A and
      ETB subtypes) display expression in numerous tissues and possibly mediate
      autocrine/paracrine actions. The present investigation shows that ET-1 triggers
      biphasic increases of the concentration of cytoplasmic Ca2+ ([Ca2+]i) in
      pathological human parathyroid cells. Both the peak and sustained [Ca2+]i
      increase, as well as the proportion of responding cells, are dose-dependent in
      the 10(-10)-10(-7) mol/L range of ET-1. In absence of external Ca2+, the ET-1
      induced [Ca2+]i peak is attenuated. ET-3 has no effect on [Ca2+]i indicating
      functional dominance of the ETA receptor subtype. ET-1 (10 nmol/L) lowers
      parathyroid hormone secretion in 0.5 mmol/L but not in higher external Ca2+
      concentrations, and parathyroid cell ET release is inhibited by increases of
      external Ca2+. Fibroblasts overgrowing the parathyroid chief cells during
      monolayer culture respond to ET-1 with biphasic [Ca2+]i increases or repetitive
      [Ca2+]i spikes, but show no response to elevation of external Ca2+. These
      findings imply that ET secretion and ET receptor expression may constitute an
      autocrine/paracrine mechanism in the regulation of human PTH secretion.

PMID- 9633828
TI  - Signaling pathways in the induction of c-fos and c-jun proto-oncogenes by 3
      methylcholanthrene.
AB  - 3-methylcholanthrene (MC), a potent promutagen and procarcinogen, is also an
      inducer of mammalian CYPIAI (cytochrome P1-450) gene. The CYPIAI enzyme is
      responsible for the detoxification of MC and its oxidation into reactive epoxide
      intermediates. Through its epoxide metabolites, MC functions also as an inducer
      of drug-metabolizing enzyme glutathione S-transferase (GST) gene expression.
      Induction of murine GST Ya gene by MC and a variety of other chemical agents is
      mediated by a regulatory element composed of two adjacent AP-1-like sites, and
      activated by the Fos/Jun heterodimeric complex (AP-1). In cultured cells, MC
      causes the induction of AP-1 activity, which is the result of an increased
      expression of c-Fos and c-Jun proteins. The mechanisms involved in MC activation
      of c-fos and c-jun gene expression were examined in the present study. Evidence
      is presented that stimulation of c-fos transcription by MC involves a signal
      transduction pathway, which includes activation of the small G protein Ras, Raf-1
      kinase, and the mitogen-activated protein (MAP) kinases, ERK1 and ERK2.
      Furthermore, we find that phorbol 12-myristate 13-acetate, which uses both
      protein kinase C and protein-tyrosine kinase activities to induce c-fos promoter,
      may share a common pathway with MC downstream of Ras. The signal transduction
      pathway induced by MC to stimulate c-jun promoter involves Ras activation and the
      JNK group of MAP-kinases.

PMID- 9633829
TI  - Responsiveness of vaginal cells to estradiol during postnatal development of rat.
AB  - Ontogeny of responsiveness to hormones is mainly regulated by the presence of
      receptors; their type, number, and location in the hormone target cells. Some of
      these parameters have been used to study the responsiveness of rat vagina to
      estradiol. The estrogen binding sites (EBS) in the cytosol of rat vagina are
      present immediately at birth, however the animal becomes responsive to the
      hormone only after 25 +/- 5 d of age. The authors demonstrate how the serum and
      tissue levels of estradiol affect the EBS in this tissue during the postnatal
      development of the rat. The various responses observed after a single i.p.
      injection of estradiol in the immature rats are explained based on the status of
      the binding sites for estrogen in this tissue.

PMID- 9633830
TI  - Demonstration of complimentarity between monoclonal antibodies (MAbs) to human
      chorionic gonadotropin (hCG) and polyclonal antibodies to luteinizing hormone/hCG
      receptor (LH-R) and their use in better understanding hormone-receptor
      interaction.
AB  - We have earlier reported that polyclonal antisera raised in rabbits to a
      luteinizing hormone/chorionic gonadotropin receptor (LH-R) purified from sheep
      luteal tissue has antibodies exhibiting hormone agonistic and antagonistic
      activities. Western blot analysis showed this antibody (LHR-anti IgG) to be
      highly specific to sheep luteal LH receptor (LH-R) (Jeyakumar and Moudgal, 1991).
      Using this, along with a battery of mouse monoclonal antibodies (MAbs) to hCG, an
      attempt has been made to better understand the interaction of LH/hCG with its
      receptor. Of the eight hCG MAbs screened, three (B14/B7, B52/18 and A7/G4) were
      specific to the beta-subunit; while a second set of three (G10/F7, H9/E9 and
      B52/21) were specific to the alpha-subunit. Two additional MAbs (B52/28 and
      F9/G8) did not recognize individual subunits, but bound like the rest intact hCG.
      Both 125I hCG and 125I anti LHR-IgG bound specifically to ovine luteal membrane
      LH-R. Assuming that a certain degree of similarity should exist between hCG and
      LHR-anti IgG, different hCG MAbs were tested for their ability to block the
      binding of either 125I hCG or 125I LHR-anti IgG to sheep luteal LH-R. It appears
      that hCG and LH-R share a minimum of four sites that are complementary to each
      other and these are recognized by the hCG MAbs B14/B7, G10/F7, A7/G4, and H9/E9.
      Whereas two of the MAbs B14/B7 and G10/F7 blocked the binding of both 125I
      labeled hCG and LHR-anti IgG to the receptor, MAbs A7/G4 and H9/E9 only inhibited
      the binding of 125I LHR-anti IgG to the LH-R. Although individually B14/B7 and
      G10/F7 blocked the binding of 125I LHR-anti IgG to LH-R to a maximum extent of
      43%, together they inhibited binding by as much as 80%. The ability of B14/B7 to
      inhibit binding of 125I LHR-anti IgG to the receptor was also significantly
      increased by the addition of A7/G4. Finally, by demonstrating direct binding of
      the immobilized hCG MAbs B14/B7, G10/F7, A7/G4, and H9/E9 to LHR-anti IgG, we
      have been able to establish that the receptor binding sites of hCG and LHR-anti
      IgG are complementary and that a set of four sites are recognizable by the hCG
      MAbs. From the degree of interaction, it appears that two sites recognized by
      MAbs B14/B7 and G10/F7 (representing a site each in the beta- and alpha-subunit
      of hCG) have a prominent role in the interaction of hCG with its receptor. Thus,
      this study has provided us with an opportunity to investigate the interaction of
      LH/hCG with its receptor by an indirect approach of monitoring the binding of
      their respective antibodies with each other.

PMID- 9633831
TI  - The New York High-Risk Project: social and general intelligence in children at
      risk for schizophrenia.
AB  - Social deficits, as well as low performance on intelligence tests, are known
      early symptoms of schizophrenia. We studied whether impairment of social
      intelligence can be detected before the outbreak of the disorder. In the New York
      High-Risk Project, children at risk for schizophrenia (HRSz) or affective
      disorder (HRAff) and a normal control group (NC) were studied over the past 26
      years. The children are now in mid-adulthood, with known psychiatric outcomes.
      Developmental and clinical data from childhood can now be related to adulthood
      diagnoses. We compared mean WISC (or WISC-R) and WAIS (or WAIS-R) scores from
      childhood and adolescence, and change of IQ, between the risk groups, as well as
      between the adulthood outcomes. We were specifically interested in the
      development of social intelligence (the Picture Arrangement and Comprehension
      subtests). We used logistic regression analyses to generate a model predicting
      adulthood schizophrenia. RESULTS: IQ at age 9,7 was lower in children with HRSz
      than with HRAff. Adulthood schizophrenia, compared with major depressive disorder
      and no psychiatric diagnosis could not be related conclusively to low IQ. This
      may be a result of the study design, since children with IQ below 70 or
      behavioral problems were not eligible as study subjects. There was no evidence of
      lower scores or more decline in social intelligence related to age or group
      membership (risk or outcome). Subtest-Scatter, a nondirectional measure of the
      differences between all subtests and Vocabulary, reflecting a lesser difference
      between crystallized and fluid intelligence, was identified as a significant
      predictor of adulthood schizophrenia, in the whole group as well as in the HRSz
      group alone.

PMID- 9633832
TI  - No serotonin 5-HT2A receptor density abnormality in the cortex of schizophrenic
      patients studied with PET.
AB  - To investigate putative abnormalities of cortical 5-HT2A receptor density in
      schizophrenia, we used positron emission tomography and [18F]setoperone, a high
      affinity 5-HT2A receptor radioligand, in 14 neuroleptic-free or -naive
      schizophrenic patients and in 15 normal controls. No significant difference
      between the groups was observed in the whole or regional cortical binding
      potential of [18F]setoperone, indicating an absence of major 5-HT2A receptor
      cortical density abnormalities in schizophrenics.

PMID- 9633833
TI  - Psychomotor slowing, negative symptoms and dopamine receptor availability--an
      IBZM SPECT study in neuroleptic-treated and drug-free schizophrenic patients.
AB  - Anhedonia and psychomotor slowing in schizophrenia have been attributed to a
      dysfunction of dopaminergic neurotransmission. To differentiate between disease
      and drug-induced negative symptoms, we examined eight drug-free and eight
      neuroleptic-treated schizophrenic patients. Positive and negative symptoms and
      extrapyramidal side effects were assessed using standardized rating scales (PSAS,
      AMDP, SANS). 'Reaction time' and 'motor speed' were measured using a computer
      aided system and striatal dopamine D2/D3 receptor availability was assessed using
      [I-123]IBZM SPECT. Psychomotor reaction time, parkinsonism, affective flattening
      and avolition were increased in treated patients relative to the untreated cohort
      and were negatively correlated with dopamine D2/D3 receptor availability.
      Significant positive correlations were found between parkinsonism and affective
      flattening and between psychomotor slowing and avolition. Positive symptoms were
      not significantly associated with striatal IBZM binding. These findings support
      the hypothesis that neuroleptic-induced dopamine D2/D3 blockade in the striatum
      can mimic certain negative symptoms, such as affective flattening and avolition,
      and indicates that psychomotor testing may be helpful in differentiating between
      disease and drug-induced negative symptoms.

PMID- 9633834
TI  - Neuropeptide Y-mediated enhancement of NMDA-stimulated [3H]dopamine release from
      rat prefrontal cortex is reversed by sigma1 receptor antagonists.
AB  - Sigma (sigma) receptors are located in limbic areas, including the prefrontal
      cortex, where decreased dopamine levels have been linked to negative symptoms.
      Although the endogenous ligands for sigma receptors are unknown, neuropeptide Y
      (NPY) has been named as the potential endogenous agonist at these receptors. NPY
      enhanced NMDA-stimulated [3H]dopamine release in rat prefrontal cortex. This was
      in contrast to the inhibition produced by the sigma agonists (+)pentazocine and
      BD737. However, four sigma antagonists, including one which is sigma1 selective,
      that reverse (+)pentazocine- or BD737-mediated inhibition all reversed the NPY
      mediated enhancement. In addition, PYX-1, a Y receptor antagonist, reversed both
      the (+)pentazocine- and BD737-mediated inhibition and the NPY-mediated
      enhancement of release. Peptide YY (PYY), [Leu31,Pro34]NPY and NPY(13-36) did not
      mimic the effect of NPY. Our findings are consistent with NPY acting as an
      endogenous ligand for a subtype of sigma receptor with characteristics different
      from Y1, Y2 and Y3 receptors but sensitive to PYX-1. These findings suggest a
      role for NPY, via sigma receptors, as a modulator of dopamine levels in the
      prefrontal cortex.

PMID- 9633835
TI  - High-energy phosphates in the frontal lobe correlate with Wisconsin Card Sort
      Test performance in controls, not in schizophrenics: a 31phosphorus magnetic
      resonance spectroscopic and neuropsychological investigation.
AB  - In recent years, a number of 31phosphorus magnetic resonance spectroscopy (P-MRS)
      studies on the frontal lobe of schizophrenics have been performed, reporting
      alterations of phospholipids and high-energy phosphates. Deicken et al. (1994b)
      recently found positive correlations between left frontal phosphomonoester%
      (PME%) levels and the performance of a specific frontal lobe task, the Wisconsin
      Card Sorting Test (WCST), in schizophrenics. In the present paper, the
      correlations between phospholipids and high-energy phosphates in the frontal lobe
      of 26 schizophrenics and 23 controls measured with a volume-selective P-MRS
      method were investigated. Overall, we could not find any correlations between
      WCST results and phospholipid levels, but in controls phosphocreatine% (PCr%) and
      PCr/adenenosine triphosphate (ATP) ratios were negatively correlated with test
      performance. Since PCr behaves as a buffer of ATP, in the sense that when ATP is
      consumed by neuronal activity PCr is catalysed rapidly to ATP, increased PCr%
      values and, moreover, increased PCr/ATP ratios point to a decreased ATP
      consumption. Thus, the correlations found between PCr% and PCr/ATP and test
      performance in controls point to an association between reduced performance in a
      specific frontal lobe task and decreased energy demanding processes at rest. This
      association was not found in schizophrenics, possibly due to the influence of
      neuroleptic medication or the disease process per se.

PMID- 9633836
TI  - Increased levels of CD8+ and CD4+ 45RA+ lymphocytes in schizophrenic patients.
AB  - Peripheral blood (PB) lymphocyte subpopulations, IgG, IgM, IgA and IgE serum
      immunoglobulins and C3 and C4 complement fractions were evaluated in 29
      schizophrenic patients, 31 of their relatives and 20 healthy subjects. The
      patients fulfilled DSM-III criteria for schizophrenia, and were unmedicated for 3
      months prior to the PB sample collection. When compared to healthy controls and
      their own relatives, the schizophrenic patients showed a lower level of CD4+
      cells, while the CD4+ 45RA+ (naive) subset was significantly higher. Conversely,
      the number of CD4+ 45RA- (memory) lymphocytes was significantly lower in
      schizophrenic patients in comparison to their relatives and controls, while the
      CD8+ supressor/cytotoxic T-cell percentage was significantly higher. No
      significant differences were observed for the IgG, IgM, IgA, IgE and C3 and C4
      complement fraction levels among the three groups. The present data confirm the
      presence of immunological abnormalities in schizophrenic patients and suggest a
      possible role of environmental factors in the triggering of an autoimmune
      pathogenic mechanism.

PMID- 9633837
TI  - The structure of schizophrenic symptoms: a meta-analytic confirmatory factor
      analysis.
AB  - To quantitatively review all presently available evidence about the
      interrelations between positive and negative schizophrenic symptoms, we created
      an aggregate matrix of the intercorrelations among schizophrenic symptoms by
      combining data from 28 independent samples using meta-analytic procedures (net
      bivariate dfs ranging from 683 to 1657). Using confirmatory factor analyses, we
      then statistically compared four theoretically derived models of the structure of
      schizophrenic symptoms. Although a three-factor model (Liddle, 1987) best fit the
      data, results suggest that either more factors or different symptoms are required
      to account well for the latent structure underlying schizophrenic symptomatology.
      The nature of such augmented approaches, the opportunities and constraints
      inherent to multifactorial models, and the limitations of current instruments are
      discussed.

PMID- 9633838
TI  - Clinical pathways and treatment algorithms in oncology patients: "not bad" but
      are they beneficial?

PMID- 9633839
TI  - Epidemiology and risk assessment for ovarian cancer.
AB  - The incidence of ovarian cancer varies internationally with higher rates among
      women of North America and northern Europe. In the United States, there has been
      relatively little change in the incidence of ovarian cancer in recent decades.
      The incidence rate of ovarian cancer is highest among white and Hawaiian women,
      intermediate among African-American, Hispanic and Asian-American women, and
      lowest among Native American women. The most intensively studied risk factors
      have been family history, pregnancy history, and oral contraceptive use.
      Multiparity, lactation, oral contraceptive use, and tubal ligation/hysterectomy
      all decrease a woman's risk of ovarian cancer. One exposure that has been
      consistently associated with increased ovarian cancer risk is cosmetic talc
      applied to the perineum.

PMID- 9633840
TI  - Genetics and ovarian carcinoma.
AB  - Ovarian cancer is a disease that will affect approximately 1% of American women
      during their lifetime, and contributes to more than 14,000 deaths annually. If
      not detected early, this disease has a 5-year survival rate of less than 20%.
      Ovarian cancer develops predominantly from the malignant transformation of a
      single cell type, the surface epithelium. Although the biological mechanisms of
      transformation remain unclear, it is probably a multistep process requiring an
      accumulation of genetic lesions in a number of different gene classes. Several
      proto-oncogenes, such as AKT2 and Ki-RAS, are activated during ovarian cancer
      development, with putative oncogene-containing chromosomal regions showing
      imbalances and DNA amplifications. A number of chromosomal regions are also lost
      in ovarian tumors, indicating that the inactivation of tumor suppressor genes,
      such as TP53, may also contribute to cancer development. An important recent
      advancement in the field of ovarian cancer research is the identification of the
      breast/ovarian cancer susceptibility genes, BRCA1 and BRCA2. Mutations in these
      two tumor suppressor genes are responsible for the majority of heritable forms of
      epithelial ovarian cancers. A second class of genes involved in DNA mismatch
      repair (MMR) are responsible for most cases of hereditary nonpolyposis colorectal
      cancer (HNPCC). HNPCC or Lynch II cancer syndrome patients are also at an
      increased risk for developing ovarian cancer. Individuals in cancer-prone
      kindreds are currently being screened for germline mutations in BRCA1, BRCA2, and
      several MMR genes (eg, MSH2, MLH1), and mutant allele carriers counseled for
      cancer risks. Issues related to counseling and management of women at high risk
      for developing ovarian cancer are discussed. Although BRCA1, BRCA2, and a number
      of MMR genes have been identified, many more genes involved in gynecologic
      malignancies remain to be discovered and the clinical significance of the cancer
      genes already known is still in its infancy.

PMID- 9633841
TI  - The biology of ovarian cancer.
AB  - The biology of ovarian cancer broadly defined covers essentially all aspects of
      the disease from how it arises to how it responds to chemotherapy, often becomes
      refractory to treatment, and ultimately kills the patient. In this article, we
      take the liberty of discussing many of these issues to some degree in context of
      the "natural/clinical" history/biology of the disease. We focus on concepts of
      how the disease develops, efforts to identify histologic changes that may precede
      the development of overt ovarian cancer, efforts to define how the growth and
      function of the normal ovarian surface epithelium are regulated to gain insights
      into how aberrant function of these pathways may contribute to the initiation of
      the disease, molecular biological studies on clinical ovarian cancer specimens,
      efforts to experimentally induce the malignant transformation of ovarian surface
      epithelial cells, and efforts to understand why ovarian cancer is often initially
      responsive to chemotherapy but ultimately becomes refractory.

PMID- 9633842
TI  - Prognostic factors in ovarian cancer.
AB  - There is obvious merit in being able to accurately predict outcome and tailor
      treatment according to individual risk and potential for benefit. Epithelial
      ovarian cancers are characterized by a broad spectrum of biological behavior
      ranging from tumors that have an excellent prognosis and high likelihood of cure
      to those that progress rapidly and have a very poor prognosis. This wide clinical
      spectrum is partly reflected by a number of clinicopathological prognostic
      variables which include International Federation of Gynecology and Obstetrics
      stage, histologic subtype and grade, volume of residual tumor remaining after
      surgical resection, performance status, and age. There has been increasing
      interest by many groups to incorporate the independent prognostic variables into
      multivariate models that could better predict outcome. This approach does appear
      to allow the identification of different prognostic subsets and requires
      confirmation in prospective studies. There has been, and there continues to be a
      lot of effort in identifying new prognostic factors that have a biologic
      rationale and these will be discussed. Most of these new prognostic factors have
      not been subjected to rigorous testing and this will be clearly necessary before
      they find clinical application. This is an area that is rapidly evolving with the
      increased understanding of the molecular basis for ovarian carcinogenesis and
      progression coupled with technological advances such as DNA arrays and automated
      polymerase chain reaction. We are at the threshold of developing a new and more
      objective as well as rational approach to predict prognosis and response to
      therapy.

PMID- 9633843
TI  - Ovarian cancer screening.
AB  - Despite advances in molecular biology, surgical oncology, and chemotherapy, the
      prognosis for ovarian cancer remains poor. The excellent survival rates for stage
      I disease provide the rationale for efforts to screen for early-stage ovarian
      cancer. However, there are doubts about the feasibility of screening related to
      the natural history of the disease, the performance of the available tests, and
      health economic considerations. The investigators use the World Health
      Organization criteria for a screening program as a framework for discussing
      current issues in ovarian cancer screening. These include screening modalities
      and strategies, high- and low-risk populations, and the acceptability,
      psychological impact, and cost of screening. As a result of developments during
      the last decade, there are now real prospects for practical and effective ovarian
      cancer screening programs. Research to date has made important progress, but
      information about the impact of screening on mortality from ovarian cancer is
      still awaited. Three large randomized controlled trials of ovarian cancer
      screening are currently recruiting volunteers and will yield important results in
      the next few years.

PMID- 9633844
TI  - The role of surgery in the management of ovarian cancer: primary and interval
      cytoreductive surgery.
AB  - Ovarian cancer remains the number one cause of mortality in gynecologic
      malignancies and the fifth most common cause of death among all malignancies in
      women. Unfortunately, recent data confirm that only approximately 90% of
      "apparent" early ovarian cancer are inadequately staged, and only approximately
      80% of patients with advanced-stage disease are adequately staged. Interval
      debulking surgery, a newer treatment modality, appears to have a promising role
      for patients who cannot be adequately debulked at their initial surgery. Second
      look laparotomy continues to be the most accurate way to document responses to
      chemotherapy in protocol settings, but additional clinical trials with newer
      second-line chemotherapy will be necessary before definitive statements can be
      made with regard to survival advantages in patients who undergo second-look
      laparotomy.

PMID- 9633845
TI  - Management of early ovarian cancer.
AB  - About one third of the women diagnosed with ovarian cancer present with localized
      disease. Accurate surgical staging is required to properly evaluate these
      patients, define appropriate treatment, and establish prognosis. A series of
      recent studies have clarified which patients can be managed with comprehensive
      surgical staging and disease removal alone, and which may benefit from adjuvant
      therapy. A series of national and international prospective randomized trials are
      evaluating a variety of adjuvant treatments that may enhance long-term survival
      in those patients with early ovarian cancer who do require additional therapy.

PMID- 9633846
TI  - Chemotherapy of advanced ovarian cancer.
AB  - Combination chemotherapy with paclitaxel plus a platinum compound (carboplatin or
      cisplatin) is the current regimen of choice for the treatment of advanced
      epithelial ovarian cancer. The two most widely used combinations are paclitaxel
      (135 mg/m2, 24-hour infusion) plus cisplatin (75 mg/m2) or paclitaxel (175 mg/m2,
      3-hour infusion) plus carboplating dosed to an area under curve of 7.5.
      Randomized trials are in progress comparing these two regimens. Numerous other
      clinical issues remain regarding how to maximize the effectiveness of this
      therapy, including dose and schedule, duration of treatment, route of
      administration, and incorporation of other agents with novel mechanisms of
      cytotoxicity. New agents currently undergoing evolution as part of novel
      induction regimens have been shown to have significant activity in recurrent
      ovarian cancer and include topotecan, gemcitabine, oral etoposide, and
      encapsulated doxorubicin.

PMID- 9633847
TI  - Multiple cycles of high-dose chemotherapy for ovarian cancer.
AB  - Recent advances in hematopoietic support have extended the application of high
      dose chemotherapy in the treatment of malignancy. The use of colony-stimulating
      factors and peripheral blood progenitor cells significantly have decreased the
      morbidity and mortality of such treatment compared with traditional autologous
      bone marrow transplantation. These innovations facilitate the use of multiple
      cycles of high-dose chemotherapy as consolidation after achieving best response
      to conventional chemotherapy or as initial treatment. Developing data suggest
      that this approach in both of these settings merit further evaluation for the
      treatment of epithelial ovarian carcinoma.

PMID- 9633848
TI  - Intraperitoneal therapy of ovarian cancer.
AB  - During the past decade, intraperitoneal chemotherapy has evolved from a
      theoretical concept into a rational therapeutic strategy for a select group of
      individuals with ovarian cancer. Patients who may potentially benefit from this
      approach include those with small volume intraperitoneal disease at the
      initiation of initial chemotherapy and individuals with microscopic and very
      small volume macroscopic cancer after the completion of front-line systemic
      treatment. Further exploration to define an ultimate role for regional
      antineoplastic drug delivery in the management of ovarian cancer is warranted.

PMID- 9633849
TI  - Update on the role of radiotherapy in ovarian cancer.

PMID- 9633850
TI  - Management of borderline tumors of the ovary: state of the art.
AB  - Evidence published during several decades has shown that there is a group of
      epithelial ovarian tumors having histological and biological features between
      those of clearly benign and frankly malignant tumors. In 1963, FIGO accepted an
      intermediate group of ovarian carcinomas of low malignant potential. In 1973, WHO
      adopted the term borderline malignancies to describe these tumors. Borderline
      tumors represent approximately 10% to 15% of all epithelial ovarian malignancies.
      There are considerable discrepancies in the reported incidence of ovarian tumors
      of borderline malignancies. Some centers do not recognize tumors of this type and
      include them among invasive cancers. The prognosis for patients with borderline
      tumors is generally considered to be excellent. Although the standard treatment
      for older patients is abdominal hysterectomy and bilateral salpingo-oophorectomy,
      many young patients who have not completed childbearing can be safely treated
      with unilateral salpingo-oophorectomy coupled with comprehensive surgical
      staging, thereby preserving fertility potential. Even ovarian cystectomy has been
      reported, but the recurrence rate in the ovary approximates 15%. Many experts
      strongly believe that surgery is the only effective treatment for borderline
      tumors. Others routinely use postoperative chemotherapy for at least some subsets
      of patients with peritoneal implants. Currently, insufficient information is
      available to make a definitive statement regarding the efficacy of postoperative
      therapy. Nevertheless, clinicians are faced with the difficult task of making
      treatment recommendations to anxious patients. In the past, extensive application
      of automated methods for analytical cytology has resulted in large quantities of
      data on ploidy abnormalities in different types of human cancers. The main
      purpose has been to obtain additional parameters for the characterization of
      various types of malignancy to give more precise information on their biological
      behavior. Data from the Norwegian Radium Hospital showed that the majority of
      borderline tumors have DNA diploid tumors and good prognosis, DNA aneuploidy
      indicates high risk. Several other investigators have shown the same results on
      DNA ploidy as a predictor of recurrence and survival, but a few others have shown
      conflicting results. Early studies suggest that p53 mutation does not appear to
      play a role in the pathogenesis of these tumors. Studies on other molecular
      markers have not yet uncovered a reliable predictor of biologic behavior.
      However, it is hoped that future studies of genetics and molecular biology of
      these tumors will lead to useful laboratory tests.

PMID- 9633851
TI  - Biological therapy of ovarian cancer: current directions.
AB  - Despite recent advances in the chemotherapy of ovarian cancer, the development of
      alternative therapies that retain activity against drug-resistant tumors remains
      a high priority. Our knowledge regarding growth factors, cytokines, and the
      immune response continues to expand, and molecular biology has provided an
      increased diversity of reagents for clinical evaluation. This review focuses on
      regulatory targets in ovarian cancer, including Her2/neu (c-erbB2) and other
      growth factor receptors; interferons, interleukins, and other immunoregulatory
      cytokines; cellular adhesion molecules; antigen-specific T lymphocytes and
      adoptive immunotherapy; choice of monoclonal antibody reagents and advances in
      antibody engineering, including recombinant single-chain binding sites, chimeric
      proteins, radioconjugates, cytotoxic drug conjugates, immunotoxins, and
      bispecific antibodies. Although specific roles for biologic therapy in the
      management of ovarian cancer have yet to be defined, current priorities for
      clinical research are reviewed.

PMID- 9633852
TI  - Gene therapy for ovarian carcinoma.
AB  - Originally conceived and applied for the treatment of inherited monogenetic
      defects such as adenosine deaminase deficiency and cystic fibrosis, gene therapy
      was later applied to the treatment of cancer. Such a genetic strategy seemed
      rational given the recognition that cancer typically develops in a multistep
      process involving alterations of a number of different genes as demonstrated in
      familial polyposis and colorectal cancer through the work of Vogelstein et al.
      Because of the numerous alterations that may result in the eventual development
      of cancer, there is no obvious single choice for a therapeutic gene. Although one
      may view this as an obstacle, it also allows for a variety of possible
      therapeutic interventions. This review focuses on the known genetic defects that
      occur in ovarian cancer, the gene therapy strategies suggested by such defects,
      and the approaches under current development for the treatment of this disease.
      As such, this work also describes some of the approved human gene therapy
      protocols. Finally, an overview of the problems and directions for future growth
      and research is presented.

PMID- 9633853
TI  - Ovarian germ cell tumors: an update.
AB  - Ovarian germ cell tumors, while very rare, are important beyond their incidence
      because they occur in young people and they are highly responsive to appropriate
      treatment. Since 1991, when this topic was last discussed in Seminars in
      Oncology, there have been a few important publications specifically devoted to
      ovarian germ cell tumors. In addition, a number of important studies have added
      to the knowledge base of chemotherapy in testis cancer. This article reviews and
      updates progress made in this field.

PMID- 9633854
TI  - Multi-ethnicity.

PMID- 9633855
TI  - Smoking estimate correction.

PMID- 9633856
TI  - WHO announces flu vaccine formula for 1998-1999.

PMID- 9633857
TI  - Surveillance for avian influenza continues.

PMID- 9633858
TI  - Vaccines under development could save up to eight million lives yearly.

PMID- 9633860
TI  - U.S. and Russia cooperate in infectious disease research.

PMID- 9633859
TI  - Comprehensive survey of working women's health issued.

PMID- 9633861
TI  - Ways to stop family violence need to be evaluated.

PMID- 9633862
TI  - Children's health insurance.

PMID- 9633863
TI  - Public Health Service: on the job for 200 years.

PMID- 9633864
TI  - Health cost containment: what it will mean for workers and local economies.
AB  - After decades of rapid growth, the rate of increase in health services spending
      appears to be moderating. Although a slowdown in health expenditure growth would
      release resources for other uses in the economy, concerns have been raised about
      the effects of a spending slowdown on health workers and regional economies.
      Based on projections carried out by the Bureau of Labor Statistics during the
      health reform debate and on state health sector employment data, the author
      concludes that health workers may experience costly dislocation as health
      spending growth slows, and some regions may be more affected than others.
      However, the appropriate response is a general economic policy supporting
      economic growth and full employment policy with regard to health expenditure
      growth cannot be held hostage to concerns about employment effects.

PMID- 9633866
TI  - Poisoning mortality, 1985-1995.
AB  - Poisoning was reported as the underlying cause of death for 18,549 people in the
      United States in 1995 and was ranked as the third leading cause of injury
      mortality, following deaths from motor vehicle traffic injuries and firearm
      injuries. Poisoning was the leading cause of injury death for people ages 35 to
      44 years. Poisoning death rates were higher in 1995 than in any previous year
      since at least 1979. From 1990 to 1995, the age-adjusted rate of death from
      poisoning increased 25%; all of the increase was associated with drugs. About
      three-fourths of poisoning deaths (77%) in 1995 were caused by drugs. The age
      adjusted rate of drug-related poisoning deaths for males (7.2 per 100,000) in
      1995 was more than twice that for females (3.0 per 100,000). From 1985 to 1995,
      poisoning death rates for males ages 35-54 years nearly doubled to 20.4 per
      100,000, and the drug-related poisoning death rate for males ages 35-54 years
      nearly tripled, reaching 16.1 per 100,000. From 1990 to 1995, death rates
      associated with opiates and cocaine more than doubled among males ages 35-54
      years. The numbers of opiate and cocaine poisoning deaths for 1995 more than
      doubled when all multiple cause of death codes were examined instead of only the
      underlying cause of death codes.

PMID- 9633868
TI  - Should the vaccine injury compensation program be expanded to cover adults?
AB  - In 1996, the National Vaccine Advisory Committee (NVAC) asked for a review of the
      pros and cons of including adult influenza and pneumococcal vaccines in the
      Vaccine Injury Compensation Program (VICP). The authors, as staff to the
      subcommittees charged with undertaking this assessment, looked at the following
      questions: (a) Would inclusion in VICP of these two vaccines, used primarily for
      adults, increase adult vaccination levels? (b) Is this Federal involvement
      warranted based on the liability burden for these vaccines? (c) Does the risk of
      adverse events following vaccinations warrant inclusion of these vaccines? (d) Is
      there a consensus among stakeholders favoring their inclusion? To address these
      questions, the authors reviewed information on adult vaccines, including data on
      l lawsuits filed and reports of injuries, and sought input from interested
      groups. They found no evidence that the use of influenza and pneumococcal
      vaccines would increase if they were included in VICP. They found a low liability
      burden for these vaccines, that serious adverse events were rare, and that no
      consensus existed among stakeholders. After considering the staff report, NVAC
      chose, in 1996, not to advise the Department of Health and Human Services to
      include adult vaccines in VICP.

PMID- 9633870
TI  - Defining the rabies problem.

PMID- 9633871
TI  - The cost of rabies postexposure prophylaxis: one state's experience.
AB  - OBJECTIVE: This study was undertaken to evaluate trends in the use of rabies
      postexposure prophylaxis (PEP) before, during, and following an epidemic of
      raccoon rabies in Massachusetts. METHODS: The authors reviewed initiation of PEP
      as reported to the Massachusetts Department of Public Health (MDPH) from August
      1994 to December 1995 and surveyed hospital pharmacies to determine the number of
      vials of Human Rabies Immune Globulin (HRIG) dispensed from 1991 through 1995 and
      charges to patients per vial. RESULTS: PEP use increased dramatically, from 1.7
      per 100,000 population in 1991 (pre-epidemic) to 45 per 100,000 in 1995 (after
      the first stages of the epidemic). The median costs per patient for biologics was
      $1646 (range: $632-$3435). Including physician and emergency room charges, per
      patient median costs were $2376 (range: $1038-$4447). Total health care charges
      for PEP in Massachusetts in 1995 were estimated at $2.4 million to $6.4 million.
      CONCLUSIONS: Given the rapid increase in use of PEP, further studies should be
      undertaken to determine the appropriateness of use, and other alternatives, such
      as oral wildlife vaccines, should be considered.

PMID- 9633872
TI  - Dog and cat bites: epidemiologic analyses suggest different prevention
      strategies.
AB  - OBJECTIVE: To examine the characteristics of reported dog and cat bite incidents
      in El Paso, Texas, and their implications for local bite prevention programs.
      METHODS: The authors reviewed a random sample of reported dog bites and all
      reported cat bites in El Paso, Texas, in 1995 using existing animal control
      surveillance data. RESULTS: The majority of cat bites (89.4%) were provoked, with
      females (57.5%) and adults (68.3%) more likely to be victims than males or
      children. In contrast, just under half of dog bites (44.6%) were provoked, with
      males (65.6%) and children (63%) more likely to be victims than females or
      adults. Dogs that had not been vaccinated for rabies were involved in 65% of dog
      bites and cats that had not been vaccinated for rabies were involved in 92% of
      cat bites. CONCLUSION: Effective bite prevention programs should address the
      finding that both restrained and unrestrained dogs may bite even when unprovoked
      and that unrestrained cats usually bite when provoked.

PMID- 9633873
TI  - Potential rabies exposures in a Virginia county.
AB  - OBJECTIVE: Although records of animal bites and scratches are kept at most local
      health departments, little is known about the epidemiology and characteristics of
      these potential rabies exposures on a local level. Bite and scratch records for a
      four-and-a-half-year period from Montgomery County, Virginia, were examined in
      order to identify preventable trends. METHODS: The author retrospectively
      reviewed animal bite and scratch records from the Montgomery County Health
      Department dating from January 1992 through July 1996. RESULTS: Cat bites or
      scratches involved stray or feral animals more than eight times as often as dog
      bites or scratches. Cats were involved in the majority of incidents in which
      rabies postexposure prophylaxis (PEP) was recommended. Overall, PEP was
      recommended following 5.9% of reported incidents. The records also indicated that
      65% of owned cats were unvaccinated at the time of the incident, while only 28%
      of owned dogs were unvaccinated. Children under the age of 18 were significantly
      more likely to be involved in a potential exposure than adults. CONCLUSIONS:
      Potential exposures should be analyzed periodically by local health departments.
      Suggestions for minimizing the number of potential rabies exposures in Montgomery
      County based on the results of the study reported here include: reducing the
      stray and feral cat population, targeting educational programs to children, and
      encouraging owners to vaccinate their pets.

PMID- 9633874
TI  - The effect of using "race of child" instead of "race of mother" on the black
      white gap in infant mortality due to birth defects.
AB  - OBJECTIVE: For at least 20 years, birth defects have been the leading cause of
      infant mortality in the United States. Some studies have reported higher rates
      for black infants than white infants of mortality due to birth defects, while
      other studies have reported no black-white differences. The authors analyzed the
      effect on these rates of a change in the way the National Center for Health
      Statistics (NCHS) tabulates "race" for newborns. METHODS: The authors calculated
      infant mortality rates due to birth defects for 1980-1993 using two standard
      methods of assigning newborns to "racial" categories: a "race of child" algorithm
      and the "race of mother" approach currently used by NCHS. RESULTS: From 1980
      through 1993, birth defect-specific infant mortality rates (BD-IMRs) were
      significantly higher for black infants than white infants 12 of the 14 years by
      "race of mother" and only 5 of 14 years by "race of child." Calculation of BD
      IMRs by "race of mother" reduced the rate for white infants and increased the
      rate for black infants in each of the 14 years. The choice of method for
      assigning newborns to "racial" categories had a progressively greater effect over
      time on the black-white gap in BD-IMRs. CONCLUSIONS: Calculations of trends in
      "race"-specific BD-IMRs by may vary substantially by whether "race of mother" or
      "race of child" is used. Identifying the method of tabulation is imperative for
      appropriate comparisons and interpretations.

PMID- 9633875
TI  - The use of infrared ear thermometers in pediatric and family practice offices.
AB  - OBJECTIVE: To describe the use of infrared (IR) ear thermometers in pediatric and
      family practice offices. METHODS: The authors mailed a questionnaire to 350
      randomly selected members of the American Academy of Pediatrics and to 355
      randomly selected members of the American Academy of Family Physicians. RESULTS:
      Of respondents in clinical practice, 78% had used IR ear thermometers at least
      once in the past; 65% of pediatricians and 64% of family practice physicians were
      current users. Seventeen percent of pediatric offices and 18% of family practice
      offices that had used IR ear thermometers had discontinued use, most citing
      inaccuracy or lack of staff trust in the device. Pediatric offices were less
      likely than family practice offices to use the device in well neonates and sick
      neonates and more likely to use it in sick children. Advantages cited included
      rapid readings, ease of use, and accuracy. Seventy-five percent of current users
      reported at least one problem, including low readings and lack of staff trust.
      CONCLUSIONS: IR ear thermometers are widely used in pediatric and family practice
      offices. Some offices limit use of these devices to older children and adults,
      and most of the offices surveyed report using other devices as a check on the
      accuracy of IR thermometers. Statements by professional organizations that
      provide user guidelines and establish appropriate age cut-offs would be helpful.

PMID- 9633876
TI  - Prevalence and correlates of dementia: survey of the last days of life.
AB  - OBJECTIVES: To estimate the prevalence and correlates of dementia at death and to
      assess the usefulness of death certificate data in the reporting of dementia.
      METHODS: The authors analyzed next-of-kin interviews for 599 male and 628 female
      decedents using data from the National Institute on Aging's Survey of the Last
      Days of Life. RESULTS: Death certificate data in this population show the
      prevalence of dementia to be less than 1%, consistent with previous reports based
      on death certificates but a substantial underestimate compared to the 11.9%
      reported in a national survey. Using a dementia index based on the informant's
      report of whether the decedent had been diagnosed with a dementing illness and
      the extent of her or his cognitive and functional limitations, this study found a
      prevalence of dementia of 8.5%. A high score on the dementia index was
      significantly associated with older age, Parkinson's disease, and incontinence.
      Lower relative odds for dementia at death were found for people with either a
      lifetime history or a death certificate report of cancer. Similarly, people with
      a lifetime history of coronary heart disease were found to have lower relative
      odds for dementia at death. CONCLUSION: These results suggest that informant
      interviews may be a useful source of data to examine factors associated with
      dementia and to estimate the prevalence of dementia in the last year of life.

PMID- 9633877
TI  - Iron chelators for thalassaemia.

PMID- 9633878
TI  - Red cell morphology and malaria anaemia in children with Southeast-Asian
      ovalocytosis band 3 in Papua New Guinea.
AB  - Southeast-Asian ovalocytosis (SAO) was diagnosed in children from Madang, Papua
      New Guinea, by detection of the SAO band 3 gene variant using the polymerase
      chain reaction. SAO band 3 was present in 16/241 (6.6%) children living in the
      community and 32/389 (8.2%) children with acute Plasmodium falciparum malaria
      (P=0.42). SAO band 3 was detected in 8.2% (23/281) of alpha+-thalassaemia
      homozygotes, 9.4% (20/214) of heterozygotes and 2.4% (2/85) of children with a
      normal alpha-globin genotype (P=0.12). The most consistent feature of SAO band 3
      on microscopy of thin blood films was red cells with two or more linear or
      irregularly-shaped pale regions. In children living in the community, these were
      present in 15 with SAO band 3 (sensitivity 93.8%) and only two normals
      (specificity 99.1%). The presence of > or = 20% ovalocytosis was a poorer
      indicator of SAO band 3 (sensitivity 68.8% and specificity 100%). Haematological
      data were similar in SAO band 3 and normal children. However, in children with
      acute malaria, haemoglobin levels and red cell counts were significantly lower in
      SAO band 3 than normal children. The degree of ovalocytosis was lower in children
      with SAO band 3 during acute malaria, suggesting that a selective loss of
      ovalocytes may contribute to malaria anaemia in Southeast-Asian ovalocytosis.

PMID- 9633879
TI  - Liver iron and fibrosis during long-term treatment with deferiprone in Swiss
      thalassaemic patients.
AB  - Serum ferritin levels, hepatic histology and iron concentration were studied in a
      'veteran' group of seven Swiss beta-thalassaemic patients after 93-99 months of
      treatment with the oral iron chelator deferiprone (L1), and another four patients
      who had received 54-82 months of L1 therapy. Despite continuous compliance,
      unexplained resurgence of serum ferritin levels occurred in 4/7 patients of the
      'veteran' group after 4-5 years on L1. In three of these a concomitant increase
      of liver iron was also observed. Hepatic histology revealed significantly higher
      degrees of fibrosis in 6/11 hepatitis C (HC)-positive patients (fibrosis scores 1
      5, mean 3.0) than in the HC-negative group (fibrosis score 0-2, mean 0.8). Two HC
      negative patients had no detectable fibrosis after 98 and 93 months on
      deferiprone. Therefore the hepatic pathology in these patients cannot definitely
      be attributed as a side-effect of deferiprone. Chronic active hepatitis C and the
      accumulation of iron are the major causative factors to be considered.

PMID- 9633880
TI  - Regression of extramedullary haemopoiesis and augmentation of fetal haemoglobin
      concentration during hydroxyurea therapy in beta thalassaemia.
AB  - Hydroxyurea increases fetal haemoglobin in many patients with sickle cell
      anaemia, but its effectiveness in thalassaemia appears to be less consistent. We
      describe the response to hydroxyurea in an adult male with homozygous beta
      thalassaemia, symptomatic paraspinal extramedullary haemopoiesis, bone pain, and
      progressive tissue iron loading. Prior to therapy with hydroxyurea the
      circulating haemoglobin (Hb) concentration was 7.0 g/dl and absolute fetal
      haemoglobin concentration was 5.0 g/dl. Administration of sodium phenylbutyrate
      had induced no increase in either parameter. Subsequent therapy with hydroxyurea
      was associated with increases in total haemoglobin to 9.0 g/dl, and in fetal
      haemoglobin to 7.6 g/dl. Ineffective erythropoiesis was reduced and
      extramedullary haemopoiesis regressed during therapy.

PMID- 9633881
TI  - Plasma thrombopoietin levels in thrombocytopenic states: implication for a
      regulatory role of bone marrow megakaryocytes.
AB  - To evaluate the diagnostic value of thrombopoietin (TPO, c-mpl ligand)
      measurements, and clarify the regulatory mechanisms of TPO in normal and in
      thrombocytopenic conditions, the plasma TPO concentration was determined in
      normal individuals (n = 20), umbilical cord blood (n = 40), chronic idiopathic
      thrombocytopenic purpura (ITP; n = 16), in severe aplastic anaemia (SAA; n = 3),
      chemotherapy-induced bone marrow hypoplasia (n = 10), myelodysplastic syndrome
      (MDS; n = 11), and sequentially during peripheral blood progenitor cell
      transplantation (n = 7). A commercially available ELISA and EDTA-plasma samples
      were used for the analysis. The plasma TPO concentration in the normals and
      umbilical cord blood were 52 +/- 12 pg/ml and 66 +/- 12 pg/ml, respectively. The
      corresponding values in patients with SAA and chemotherapy-induced bone marrow
      hypoplasia were 1514 +/- 336 pg/ml and 1950 +/- 1684 pg/ml, respectively, and the
      TPO concentration, measured sequentially after myeloablative chemotherapy and
      peripheral blood progenitor cell transplantation, was inversely related to the
      platelet count. In contrast, the plasma TPO recorded in patients with ITP (64 +/-
      20 pg/ml) and MDS (68 +/- 23 pg/ml) were only slightly higher than normal levels.
      In conclusion, TPO levels were significantly elevated in patients in which bone
      marrow megakaryocytes and platelets in circulation were markedly reduced, whereas
      TPO levels were normal in ITP patients, and only slightly increased in the MDS
      patients. These latter patients displayed a preserved number of megakaryocytes in
      bone marrow biopsies. Our data support the suggestion that megakaryocyte mass
      affects the plasma TPO concentration. In thrombocytopenic patients a
      substantially increased plasma TPO implies deficient megakaryocyte numbers.
      However, TPO measurements do not distinguish between ITP and thrombocytopenia due
      to dysmegakaryopoiesis, as seen in MDS patients.

PMID- 9633882
TI  - Effects of thrombopoietin on the proliferation and differentiation of primitive
      and mature haemopoietic progenitor cells in cord blood.
AB  - Thrombopoietin (TPO) is considered to be the primary growth factor for regulating
      megakaryopoiesis and thrombopoiesis. In this study we investigated the in vitro
      effect of TPO on relatively immature and mature CD34+ progenitor cells in cord
      blood. Cells were cultured in both liquid and semi-solid cultures containing 50
      ng/ml TPO. The CD34+/CD45RA- and CD34+/CD38- subfractions in cord blood were both
      enriched for megakaryocyte progenitors as determined in a semisolid CFU-meg
      assay. Progenitor cells derived from the CD34+/CD45RA- and CD34+/CD38-
      subfractions showed high proliferative capacity in liquid cultures. We observed a
      mean 19-fold expansion of the total CD34+ cell fraction, whereas in the
      CD34+/CD45RA- and CD34+/CD38- subfractions the mean expansion was 23- and 50-fold
      respectively. The expansion of the immature progenitor cell subfractions resulted
      in a highly purified megakaryocyte suspension containing > 80% megakaryocytes
      after 14 d in culture. However, these expanded megakaryocytes remained in a
      diploid (2N) and tetraploid (4N) state. Maturation could not be further induced
      by low concentration of TPO (0.1 ng/ml). The majority of the cells were 2N (80%)
      and 4N (15%) and only 5% of the cells had a ploidy of more than 4N. These results
      indicate that megakaryocyte progenitor cells in cord blood residing in the
      immature stem cell fraction exhibit a high proliferative capacity when cultured
      in the presence of TPO as the single growth factor, without maturation to
      hyperploid megakaryocytes.

PMID- 9633883
TI  - Evidence for differences in the mechanisms by which antibodies against CD44
      promote adhesion of erythroid and granulopoietic progenitors to marrow stromal
      cells.
AB  - Adhesive interactions between haemopoietic progenitor cells and stromal elements
      involve a number of different molecules, some of which may be progenitor- lineage
      and stage-specific. CD44 is one such molecule, although little is known about
      the mechanism(s) by which it is involved. In this study, several anti-CD44
      monoclonal antibodies (mAb) increased the adherence of clonogenic cells, without
      affecting the total number of types of progenitors recoverable from the adhesion
      cultures. All of these mAb recognized epitopes on the globular head of CD44. In
      contrast, two mAb that recognized other regions of CD44 reduced progenitor
      adhesion to stroma. The mechanism by which one of the anti-CD44 mAb (L178)
      enhanced progenitor adhesion did not involve CD44-crosslinking, and was
      independent of VLA-4-, VLA-5- or LFA-1-mediated interactions, Ca or Mg cations,
      or accessory cells. In addition, CD44 expression on both progenitors and stromal
      cells contributed to L178-enhanced progenitor adhesion. Baseline adherence of
      erythroid progenitors to stroma required tyrosine kinase activity, whereas that
      of granulopoietic progenitors did not. However, the increase in adhesion did
      require tyrosine kinase activation. Additional experiments suggested that
      enhanced adhesion of CFU-GM to stroma may also be adenylate cyclase-dependent.
      Taken together, the present studies indicate both similarities and differences in
      the mechanisms of CD44-mediated adhesion of erythroid and granulopoietic
      progenitors to stromal cells.

PMID- 9633884
TI  - Interferon alpha activates the tyrosine kinase Lyn in haemopoietic cells.
AB  - We investigated whether the src-family tyrosine kinase Lyn is involved in the
      generation of interferon alpha (IFN alpha) signals in haemopoietic cells. In
      vitro kinase assays using IFN alpha-sensitive cells of B-cell origin demonstrated
      the presence of IFN alpha-dependent kinase activity in anti-Lyn
      immunoprecipitates. Further studies demonstrated that Lyn associates via its src
      homology 2 (SH2) domain with the Janus family tyrosine kinase Tyk-2. This
      interaction was IFN alpha-dependent and involved direct binding of the SH2 domain
      of Lyn to the IFN alpha-activated form of Tyk-2. Thus, during binding of IFN
      alpha to its receptor in malignant haemopoietic cells, Lyn is engaged in an IFN
      alpha-signalling pathway, probably downstream of Tyk-2.

PMID- 9633885
TI  - A warfarin induction regimen for out-patient anticoagulation in patients with
      atrial fibrillation.
AB  - Currently available protocols for induction of warfarin anticoagulation employ
      initial doses of 10 mg and are best suited to in-patient use. However, with the
      increasing number of elderly patients with atrial fibrillation requiring
      anticoagulation, there is a need for a less intense regimen which could be used
      for out-patients. We have established such a regimen and report on its
      prospective evaluation in 3 7 patients referred for out-patient initiation of
      warfarin, and a non-randomized comparison with 37 in-patients, with similar
      diagnoses, commenced on a traditional warfarin protocol. After exclusion of five
      patients on amiodarone, all of whom experienced supratherapeutic International
      Normalized Ratio (INR) results, the new out-patient regimen, employing an initial
      5 mg dose, resulted in a lower maximum INR during the first 21 d therapy (median
      2.9 v 4.0; P = 0.0001) and fewer INRs >4.5 (2/36 v 9/33) compared to the
      traditional 10 mg regimen. Time to reach stable anticoagulation was similar with
      each regimen; however, the 5 mg regimen gave a more accurate prediction of
      maintenance dose (correlation coefficient for predicted versus actual maintenance
      dose, r = 0.985). In comparison to a traditional 10 mg protocol, the proposed 5
      mg warfarin induction regimen proved both safer and more reliable for initiation
      of prophylactic anticoagulation in patients with atrial fibrillation.

PMID- 9633886
TI  - Aprotinin complements heparin bonding in an in vitro model of cardiopulmonary
      bypass.
AB  - The relative contribution of full-dose aprotinin, used with heparin-bonded
      surfaces, to contact activation during cardiopulmonary bypass was examined. In
      vitro Carmeda-bonded cardiopulmonary bypass circuits were perfused with whole
      blood anticoagulated with heparin (3.3 U/ml). Aprotinin (300 kIU/ml) was added to
      the circuits of one set of experiments. Samples were taken prior to perfusion and
      at 30, 60, 120 and 360 min. The activated coagulation time was extended in the
      aprotinin experiments, significantly at 30 min (P=0.003) and 120 min (P=0.001).
      Thrombin-antithrombin complexes and prothrombin fragment F1+2 were both higher in
      the non-aprotinin experiments at 120 min (P=0.02 each) and 360 min (P=0.005 and
      0.001, respectively). Plasma leucocyte elastase was raised in the non-aprotinin
      experiments in comparison to the aprotinin experiments at each timepoint (30 min,
      P=0.04; 60 min, P=0.006; 120 min, P=0.001; 360 min, P=0.0001), as was interleukin
      8 at 120 min (P=0.05) and 360 min (P=0.0001). No differences were found for the
      platelet activation marker P-selectin. Platelet and white blood cell counts fell
      significantly in the non-aprotinin experiments compared with the aprotinin
      experiments at 360 min (P=0.05 and 0.03, respectively). It would appear that the
      use of aprotinin has additional haemostatic beneficial effects to those found
      with heparin-bonded circuits in terms of effects on contact activation and
      inflammation.

PMID- 9633887
TI  - A comparison of artificially-depleted, lyophilized coumarin and fresh coumarin
      plasmas in thromboplastin calibration. European Concerted Action on
      Anticoagulation.
AB  - Artificially-depleted lyophilized plasmas and lyophilized coumarin plasmas were
      prepared and compared with fresh coumarin plasmas to assess their comparative
      reliability in local thromboplastin calibration using the manual prothrombin time
      (PT) technique. Their certified PT values were inserted in turn on the vertical
      axis in place of the PT obtained with fresh coumarin plasmas. PT results were
      obtained at eight ECAA national laboratories ('test centres') and inserted on the
      horizontal axis. The resulting thromboplastin calibration slopes were compared
      with conventional fresh coumarin plasma calibration slopes at the same 'test
      centres'. When 60 artificially-depleted plasmas were substituted for 60 fresh
      plasmas, the mean calibration slopes with the human plain International Reference
      Preparation (IRP) were 4.2% higher. For comparison with 20 lyophilized coumarins,
      three sets of 20 artificially-depleted plasmas were selected in sequential order
      from the 60. The lyophilized coumarin plasmas gave a mean deviation of 9.6% from
      the fresh plasma calibration slopes compared with values of 2.0%, 6.1% and 11.7%
      for the three sets of 20 depleted plasmas. Although both types of lyophilized
      plasma calibration slopes give measurable differences from conventional fresh
      plasmas, these may be regarded as acceptable in clinical terms.

PMID- 9633888
TI  - Prevalence and significance of anticardiolipin, anti-beta2 glycoprotein I and
      anti-prothrombin antibodies in chronic hepatitis C.
AB  - Antiphospholipid antibodies have been demonstrated in chronic hepatitis C, but
      their clinical and pathogenetic significance remains elusive. We prospectively
      studied 115 patients (85 men, mean age 36.9 years) with chronic hepatitis C
      without cirrhosis and treated by alpha-interferon (alpha-IFN). Antiphospholipid
      determinations comprised anticardiolipin (ACA), anti-beta2-glycoprotein I and
      anti-prothrombin antibodies of the IgG and IgM classes. At entry, 24 patients
      (21%) were found to possess low to moderate ACA levels (18 IgG, two IgM and four
      both isotypes) compared with only 4/115 age- and sex-matched control subjects
      (3.5% P=0.001). ACA positivity rate increased to 31% (P=0.01) after a 6-month
      course of alpha-IFN treatment. In contrast, the prevalence of anti-beta2
      glycoprotein I and anti-prothrombin antibodies was not significantly different
      from controls at either time point. The presence of ACA correlated with that of
      antinuclear antibodies (P=0.0002), but was not associated with parameters such as
      histological activity, viral burden and response to alpha-IFN, nor with a history
      of thrombosis or pregnancy loss. However, a non-significant trend of higher
      incidence of mild thrombocytopenia among ACA-positive patients was observed. We
      conclude that low-titre ACA positivity is a common finding in patients with
      chronic hepatitis C, especially following alpha-IFN treatment, but does not
      select a category with different clinical features. These data are in keeping
      with the absence of associated anti-beta2GPI and anti-prothrombin antibodies, and
      do not support a role for HCV infection in the pathogenesis of the
      antiphospholipid syndrome.

PMID- 9633889
TI  - Successful use of protease inhibitors in HIV-infected haemophilia patients.
AB  - The haemophilias are a group of inherited haemostatic disorders that require
      regular clotting factor replacement therapy in the severe and moderately severe
      subgroups. Prior to the introduction of adequate viral inactivation methods in
      1985, haemophilia patients were at exceptionally high risk of contracting blood
      borne viruses from factor concentrates as each batch was derived from the plasma
      of thousands of donors. As a result, approximately 60% of these patients were
      infected with HIV between 1979 and 1985, and HIV infection now contributes
      significantly to the morbidity and mortality seen in this group. Protease
      inhibitors (PIs) have been shown to significantly log reduce viral loads and
      increase CD4 cell counts in HIV-infected individuals. Recently, there has been
      concern about their use in HIV-infected haemophilia patients following increased
      bleeding episodes in some patients during PI therapy. We prospectively studied
      the effect of PI therapy in 20 HIV-infected haemophilia patients at our centre
      over a 6-month period. The mean increase in CD4 cell count was 70 x 10(6)/l and
      the mean log decrease in viral load was 1.59 over the study period.
      Gastrointestinal side-effects (nausea and vomiting in five, diarrhoea in two)
      were the most frequent and resulted in discontinuation of the medication in two
      patients. Factor concentrate usage for the group on and off study was similar.
      One severe FVIII patient reported a single episode of an unusual bleed which
      responded promptly to FVIII concentrate infusion. The significant clinical and
      laboratory benefits in terms of HIV disease and the paucity of added bleeding
      complications suggest that PI therapy should not be withheld from HIV-infected
      haemophilics. Further prospective studies evaluating the efficacy and possible
      haemostatic complications related to these promising inhibitors of the HIV
      protease are needed.

PMID- 9633890
TI  - A common polymorphism in the tumour necrosis factor-alpha gene associated with
      high TNF levels is not a risk factor for venous thromboembolism.
AB  - The odds ratio of homozygosity or heterozygosity for the TNF2 polymorphism in 575
      patients with venous thromboembolism compared to controls was found to be 1.0
      (95% CI 0.4-2.1) and 1.1 (95% CI 0.8-1.4) respectively. Comparing subgroups of
      patients and controls with the factor V Leiden mutation the odds ratio for the
      TNF2 polymorphism was 0.7 (95% CI 0.2-2.2). Despite evidence of a link between
      high tumour necrosis factor (TNF) levels and hypercoagulability, our results do
      not indicate a link between the genetic regulation of TNF production and venous
      thromboembolic disease.

PMID- 9633891
TI  - Prevention of central venous catheter associated thrombosis using minidose
      warfarin in patients with haematological malignancies.
AB  - Thrombosis is a well-recognized complication following insertion of central
      venous catheters and is associated with significant morbidity. In an attempt to
      reduce line-associated thrombosis, 108 consecutive patients with haematological
      malignancies were commenced on prophylactic 'minidose' warfarin, 1 mg/d, at the
      time of line insertion. This group of patients were compared with a historic
      group of 115 consecutive patients who had not received warfarin. Clinically
      suspected venous thrombosis was confirmed by Doppler ultrasound or venography.
      Patients taking prophylactic warfarin had their prothrombin time measured three
      times per week with the aim of maintaining an INR <1.6. Five (5%) of the 108
      patients who received minidose warfarin developed a thrombosis, at a median of 72
      d (range 5-166) from the time of catheter insertion. In the 115 patients who were
      not anticoagulated 15 (13%) developed a catheter-associated thrombosis at a
      median of 16 d (range 1-35). There was a significant reduction in line-associated
      thrombosis in patients receiving warfarin (P=0.03). These data suggest that
      minidose warfarin reduces the incidence of central venous catheter related
      thrombosis in patients with haematological malignancies.

PMID- 9633892
TI  - Gain of chromosome 7 marks the progression from indolent to aggressive follicle
      centre lymphoma and is a common finding in patients with diffuse large B-cell
      lymphoma: a study by FISH.
AB  - Gain of chromosome 7 represents one of the most frequent cytogenetic findings in
      B-cell lymphomas with a follicular growth pattern. We used fluorescence in situ
      hybridization (FISH) and a probe specifying chromosome 7 on lymph node imprints
      and/or bone marrow (BM) and peripheral blood (PB) smears from six consecutive
      patients with follicle centre lymphomas (FCLs) grade I or II (low-grade
      lymphomas), four patients with FCLs grade III and 11 patients with diffuse large
      B-cell lymphomas (DLBCLs) (high-grade lymphomas). We found gains of chromosome 7
      in 14/18 successfully analysed cases (i.e. 2/6 FCLs grade I-II, 3/3 FLCs grade
      III and in 9/9 DLBCLs) using lymph node imprints. Moreover, the FISH technique
      demonstrated gains of chromosome 7 in 1/4 BM and 0/4 PB samples from FCLs grade I
      II, in 2/4 BM and 2/4 PB specimens from FCLs grade III and in 4/9 BM and 2/9 PB
      samples from the DLBCLs. In contrast, morphologically recognizable lymphoma cells
      were seen in only 1/4 BM and 0/4 PB samples from the FCLs grade III and in 1/11
      BM and 1/11 PB samples from the DLBCLs. We conclude that: (i) gain of chromosome
      7 marks the progression from indolent to aggressive FCL and would appear to be a
      common finding in patients with FCLs grade III and in DLBCLs, (ii) clonal
      lymphoid cells occur frequently in BM and PB in high-grade lymphomas, making
      traditional staging by cytomorphology uncertain, and (iii) using gains of
      chromosome 7 as a marker of lymphoma cells, FISH is a useful method to detect
      minimal residual disease in FCLs grade III and DLBCLs.

PMID- 9633893
TI  - Human herpesvirus type 7 in Hodgkin's disease.
AB  - Several lines of evidence have pointed to the involvement of a viral agent in the
      pathogenesis of Hodgkin's disease (HD). Therefore we investigated the presence of
      human herpesvirus type 7 (HHV-7) in 53 cases of HD by polymerase chain reaction
      (PCR), DNA in situ hybridization (ISH) and immunohistochemistry. HHV-7 DNA was
      frequently detected (68% of the cases) in HD biopsies by PCR independently of the
      histological type, whereas only 32% (P<0.05) of positive cases were found in 19
      reactive lymph nodes. However, by applying the quantitative PCR technique, the
      majority of the samples showed a low level of viral load. Moreover, ISH for HHV-7
      DNA was positive in a low number of small T lymphocytes and consistently negative
      in Hodgkin and Reed-Sternberg (HRS) cells, which appeared negative for HHV-7 also
      at immunohistochemistry. These results indicate that the high frequency of HHV-7
      infection in HD: (i) is probably non-productive, (ii) mainly involves small
      lymphocytes belonging to the T-lineage, and (iii) is probably due to the
      recruitment of non-malignant reactive cells in HD tissue.

PMID- 9633894
TI  - Oligoclonal proliferation of human T-cell leukaemia virus type 1 bearing T cells
      in adult T-cell leukaemia/lymphoma without deletion of the 3' provirus
      integration sites.
AB  - We report a new case of an asymptomatic carrier with a deletion of a 3' HTLV-1
      integration site. We further investigated whether these 3' deletions of flanking
      sequences may explain the oligoclonal pattern of HTLV-1 replication, evidenced by
      inverse PCR (IPCR) analysis of tumourous samples from patients with adult T-cell
      leukaemia (ATLL). 48 HTLV-1 3' integration sites, derived from tumourous DNA of
      five ATLL patients were sequenced. One dominant flanking sequence was obtained in
      the four samples harbouring a unique band after Southern-blotting. In one sample,
      which harboured two signals after Southern-blotting, IPCR amplification of
      diluted tumourous DNA revealed that these two sequences corresponded to one clone
      harbouring two integrated proviruses rather than to two distinct cellular clones,
      a result consistent with superinfection of the tumourous sample. In addition to
      integration sites corresponding to malignant clones, two to six oligoclonal forms
      were sequenced in four samples. No flanking sequence homology was found between
      clones derived from each patient, indicating that integration sites deletion in
      the vicinity of the provirus is a rare event in ATLL. The oligoclonal pattern of
      HTLV-1 replication in ATLL may result from clonal expansion of non-malignant HTLV
      1-bearing clones within the sample and partly from HTLV-1 superinfection of
      monoclonal tumour cells.

PMID- 9633895
TI  - Large granular lymphocyte leukaemia occurring after renal transplantation.
AB  - Post-transplantation lymphoproliferative disorders (PTLD) are a
      clinicopathologically heterogeneous group of lymphoid proliferations. The
      majority are of B-cell origin and associated with Epstein-Barr virus (EBV)
      infection. In contrast, the development of T-cell PTLD is much less common and
      EBV does not appear to be involved in pathogenesis. In this report we describe
      three patients who developed large granular lymphocyte (LGL) leukaemia after
      renal transplantation. These patients had clonal expansion of CD3+, CD8+, CD57+,
      CD56- LGL. We were unable to detect CMV antigen or find evidence for EBV or human
      T-cell leukaemia/lymphoma virus genome in the LGL from these patients. These data
      show that LGL leukaemia should be included as one of the types of T-cell
      proliferations which can occur post transplant.

PMID- 9633896
TI  - Clinical characteristics of patients with de novo acute myeloid leukaemia and
      isolated trisomy 11: a Cancer and Leukemia Group B study.
AB  - Isolated trisomy 11 is the third most common sole trisomy in de novo acute
      myeloid leukaemia (AML). However, only 49 cases have been published, and for only
      a fraction of these cases has full description of clinical and haematological
      features been provided. As a result, little is known about the clinical
      characteristics of de novo AML patients with solitary trisomy 11. We have
      identified 13 patients (0.9%) with isolated trisomy 11 among a total of 1496
      consecutive adult patients successfully karyotyped as part of a prospective
      Cancer and Leukemia Group B (CALGB) cytogenetic study (CALGB 8461). Nine patients
      (69%) were over the age of 60 (range 29-73 years). Eight patients (62%) were
      diagnosed with AML of FAB M2 subtype, three patients (23%) had FAB M1 AML and one
      patient each had AML of FAB M0 and M7, respectively. Seven patients (54%) had
      high, >100 x 10(9)/l, platelet counts (median 102 x 10(9)/l; range 17-207 x
      10(9)/l). All patients received CALGB induction therapy with standard doses of
      cytarabine and daunorubicin. Six patients (46%) achieved a complete remission
      (CR). The median CR duration was 17.5 months (range 8.7-49.8). Only one patient,
      who underwent bone marrow transplantation in first CR, continues in initial CR.
      The median survival was 14.3 months (range 0.5-50.7); only one patient survives.
      We conclude that de novo AML with isolated trisomy 11 is predominantly associated
      with older age, M2 and M1 FAB subtypes, high platelet count and few long-term
      disease-free survivals, although it is currently unknown whether isolated trisomy
      11 constitutes an independent prognostic factor.

PMID- 9633897
TI  - Differential constitutive activation between STAT-related proteins and MAP kinase
      in primary acute myelogenous leukaemia.
AB  - Many cytokines and growth factors stimulate multiple signal transduction pathways
      essential for proliferation in human acute leukaemia cells, including a mitogen
      activated protein (MAP) kinase pathway and a Janus kinase (JAK)-STAT (signal
      transducers and activators of transcription) pathway. We have previously shown
      constitutive activation of MAP kinase in approximately 50% of acute myelogenous
      leukaemia (AML) samples. Recently, STAT proteins have been reported to be
      constitutively activated in 10-20% of AML cases. STAT3 and STAT5 are the main
      STAT proteins activated in haemopoietic progenitors in response to cytokines such
      as IL-3, GM-CSF, erythropoietin and thrombopoietin. Although the possibility of
      STAT1 protein as a substrate for MAP kinase at a serine residue has been
      suggested, the cross-talk between STATs and MAP kinase pathways in vivo,
      especially in leukaemia cells, remains unknown. We examined the phosphorylation
      of STAT 3 and STAT 5 at the tyrosine residues in AML samples in which MAP kinase
      activity had already been found. 40/50 primary AML cases (80%) exhibited
      constitutive tyrosine phosphorylation of STAT5. Electrophoretic mobility shift
      assay showed DNA binding activity of STAT5 correlated with tyrosine
      phosphorylation of STAT5. Similarly, with respect to STAT3, 17/23 cases examined
      (74%) showed constitutive tyrosine phosphorylation of STAT3. In addition, we
      examined the tyrosyl-phosphorylation of STAT5 isoforms, STAT5A and STAT5B, in 20
      AML cases, and found selective STAT5B phosphorylation in the absence of STAT5A
      phosphorylation in three cases. Furthermore, in certain AML cases, constitutive
      activation of MAP kinase and STAT proteins occurred independently. No significant
      correlation of MAP kinase activation was observed with either tyrosine
      phosphorylation of STAT3/STAT5 or positive DNA binding of STAT proteins. These
      results suggest that constitutive activation of STAT proteins occurs commonly and
      that the causes of constitutive activation of these two major cascades are
      heterogeneous in AML.

PMID- 9633898
TI  - Butyrate-stable monosaccharide derivatives induce maturation and apoptosis in
      human acute myeloid leukaemia cells.
AB  - The rapid degradation and subsequent lack of efficacy of n-butyric acid in vivo
      has been improved by the synthesis of monosaccharide stable pro-drugs of butyric
      acid. We studied the effects of D1 (O-n-butanoyl-2,3-O-isopropylidene-alpha-D
      mannofuranoside), G1 (1-O-n-butanoyl-D,L-xylitol), and F1 (1-O-n-butanoyl 2,3-O
      isopropylidene-D,L-xylitol) on the maturation and proliferation of AML cell lines
      HL 60 and FLG 29.1 and of purified blast cells from 10 cases of de novo acute
      myeloid leukaemia (AML). AML cell maturation was measured by surface antigen
      expression, morphology and cytochemistry. Toxicology in mice was also evaluated
      (DL50 1000 mg/kg). In HL 60 cells G1 and D1 increased the expression of CD15 and
      CD11a (presenting 62% of promyelo-metamyelocytes), and in 7/10 cases of primary
      AMLs that of CD11a, CD11b, CD15, and myeloperoxidase. D1, G1 and F1 induced a
      dose-dependent inhibition of tritiated thymidine uptake. Apoptosis (evaluated by
      flow cytometry and agarose gel electrophoresis) was induced in AML blasts by D1
      and F1 (79% and 94% respectively for HL 60 cells) and, with less effect, by G1
      (27%). The persistence of maturative and apoptotic activity in these new pro
      drugs of butyric acid, hydrolysed only inside the tumour cell, suggests a
      possible use in differentiation therapy of myelodysplastic syndromes and AMLs.

PMID- 9633899
TI  - Chemotherapeutic drug-induced apoptosis in human leukaemic cells is independent
      of the Fas (APO-1/CD95) receptor/ligand system.
AB  - The potential role of the Fas (CD95/APO-1) receptor/ligand system in
      chemotherapeutic drug-induced apoptosis was examined in a number of human
      leukaemic cell lines. Flow cytometric profiles of doxorubicin-treated HL-60,
      K562, U937 and Jurkat cells failed to show any significant increase in Fas or Fas
      ligand expression over 24 h, despite the induction of significant levels of
      apoptosis in these cells. Although preincubation of human leukaemic cells with a
      neutralizing anti-Fas IgG antibody blocked anti-Fas IgM-induced apoptosis, this
      strategy failed to inhibit chemotherapeutic drug-induced apoptosis. To determine
      whether recruitment of the Fas/Fas ligand complex during drug-induced apoptosis
      was a cell-specific event we utilized the CEM cell line. Doxorubicin treatment of
      CEM cells over 24 h failed to show any up-regulation in Fas or Fas ligand protein
      levels as detected by flow cytometry. Furthermore, neutralizing anti-Fas IgG Ab
      failed to inhibit chemotherapeutic drug-induced apoptosis in CEM cells. The
      present studies do, however, demonstrate a role for anti-Fas IgM Ab in producing
      a cytotoxic synergistic effect when used in combination with chemotherapeutic
      drugs. Low-dose anti-Fas IgM treatment in combination with doxorubicin,
      methotrexate, camptothecin and etoposide produced an augmented cytoxicity in CEM
      cells. Taken together these observations demonstrate that although recruitment of
      the Fas/APO-1/CD95 receptor/ligand system is not a necessary requirement for
      chemotherapeutic drug-induced apoptosis, combination of anti-Fas IgM and drug
      treatment produces a synergistic cytotoxic effect which may prove useful in the
      treatment of human leukaemias.

PMID- 9633900
TI  - Evidence for a critical role of DNA topoisomerase IIalpha in drug sensitivity
      revealed by inducible antisense RNA in a human leukaemia cell line.
AB  - To examine the role of human DNA topoisomerase IIalpha (topo IIalpha) in drug
      resistance, we selectively inhibited topo IIalpha gene expression in U937 human
      monocytic leukaemia cells stably transfected with a plasmid that allowed for Zn
      mediated conditional expression of a human alpha-topo IIalpha antisense sequence.
      Expression of topo IIalpha mRNA was reduced to <30%, whereas no significant
      alteration of topo IIbeta mRNA expression was observed. Under these conditions,
      drug sensitivity to the topo-II-directed agents, etoposide and daunorubicin, was
      reduced to approximately 50%, whereas sensitivity to 4-hydroperoxy
      cyclophosphamide (4-HC) was not altered. This suggests that a reduced amount of
      topo IIalpha mRNA may be sufficient for the resistance to topo II inhibitors in
      leukaemia cells.

PMID- 9633901
TI  - Interphase cytogenetics and competitive RT-PCR for residual disease monitoring in
      patients with chronic myeloid leukaemia during interferon-alpha therapy.
AB  - There is a need for fast and sensitive methods to evaluate the response of
      patients with chronic myeloid leukaemia (CML) to interferon-alpha (IFN-alpha)
      therapy to complement cytogenetic analysis of Philadelphia (Ph) chromosome
      positive metaphases. We have used interphase FISH (fluorescence in situ
      hybridization) and competitive RT-PCR (reverse transcriptase-polymerase chain
      reaction) techniques for detection of BCR-ABL-positive cells to measure
      suppression of leukaemic clone in a series of 51 follow-up samples from 24 CML
      patients undergoing IFN-alpha treatment. Interphase FISH analysis of the
      malignant clone in bone marrow using BCR and ABL probes was found to be highly
      correlated to conventional G-banding metaphase examination (r = 0.98). RT-PCR
      quantification of BCR-ABL mRNA transcripts in blood also showed a high degree of
      concordance with the proportion of Ph-positive metaphases (r = 0.93). In
      addition, the degree of cytogenetic response did not influence the equivalence
      between karyotype analysis and molecular methods. We concluded that interphase
      FISH and competitive RT-PCR provide reliable information on residual tumour
      burden and response to IFN-alpha in CML patients. These molecular methods may
      significantly improve the efficiency of residual disease monitoring during IFN
      alpha therapy of CML.

PMID- 9633902
TI  - Methylation of the p16INK4A gene in multiple myeloma.
AB  - The p16INK4A (p16) binds to both cyclin D-CDK4 and cyclin D-CDK6 and inhibits the
      progression of the cell cycle from G1 to S phase. Loss of expression of this
      protein can occur by several mechanisms including structural alterations. Recent
      studies have suggested that the loss of expression of p16 can occur by
      hypermethylation of the gene. The methylation status of the p16 gene in multiple
      myeloma was examined in three myeloma cell lines (U266, RPMI8226 and IM9) and 16
      primary myeloma samples using methylation-specific polymerase chain reaction
      (MSP). The U266 and RPMI8226 cell lines contained a completely methylated p16
      gene and the IM9 line had a partially methylated p16 gene. Identical results were
      obtained by another polymerase chain reaction (PCR)-based methylation assay
      system as well as Southern blotting after using a methylation-sensitive
      restriction enzyme. The U266 cell line expressed no p16, and the IM9 had weak
      expression as determined by reverse transcript (RT-)PCR. The U266 cells began to
      express, and IM9 increased the accumulation of, the p16 RNA after treatment with
      the demethylating agent 5'-aza-2-deoxycytidine (10(-6)-10(-5) M). This suggested
      that the levels of methylation of the p16 gene detected by the MSP technique
      correlated with the regulation of transcription of this gene. Examination of the
      primary myeloma samples showed that eight of 16 (50%) contained a methylated p16
      gene. We have previously found that alterations of the p16 gene, such as
      deletions and point mutations, are rare in primary multiple myeloma; none of the
      16 samples included in this study had p16 gene alterations. Our results suggest
      that methylation of the p16 gene may contribute to the development and/or
      progression of multiple myeloma.

PMID- 9633903
TI  - Specific depletion of alloreactive T cells in HLA-identical siblings: a method
      for separating graft-versus-host and graft-versus-leukaemia reactions.
AB  - Accumulating evidence indicates that alloreactive donor T cells confer both graft
      versus-host (GVH) and graft-versus-leukaemia (GVL) reactivity following
      allogeneic bone marrow transplantation. We have developed a method to deplete
      alloreactive donor T cells with an immunotoxin targeting the alpha chain of the
      IL-2 receptor. In patients with chronic myeloid leukaemia and their HLA-identical
      sibling donors, we measured donor helper T-lymphocyte precursor frequencies
      (HTLPf) against recipient peripheral blood mononuclear cells (PBMNC; donor versus
      host), recipient leukaemia cells (donor versus leukaemia) and third-party PBMNC,
      before and after the depletion. In seven pairs there was a 4.3-fold reduction of
      donor-versus-host HTLPf (P=0.017), without a significant change in the donor
      frequencies against third party (P=0.96). In eight further donor-recipient pairs,
      immunotoxin-depleted donor versus patient PBMNC HTLPf 4.5-fold (mean 1/155,000
      before and 1/839,000 after depletion, P=0.007). There was a smaller non
      significant 1.8-fold reduction in donor-versus-leukaemia HTLPf from 1/192,000 to
      1/334,000 (P=0.19). These results suggest that selective T-cell depletion can
      significantly deplete donor anti-host reactivity while conserving anti-leukaemia
      reactivity in HLA-matched donor-recipient pairs.

PMID- 9633904
TI  - Haemopoietic defect and decreased expansion potential of bone marrow autografts
      from patients with acute myeloid leukaemia in first remission.
AB  - Autologous bone marrow (BM) transplantation for acute myeloid leukaemia (AML) in
      complete remission (CR) is frequently followed by a slow haemopoietic recovery.
      We assessed the haemopoietic capacity of purified BM stem cell (CD34+ DR-) and
      progenitor cell (CD34+ DR+) populations from patients with AML in CR, and
      compared these data with those of normal BM. The feasibility of ex vivo expansion
      in stroma-conditioned medium supplemented with cytokines was also investigated.
      The number of CFU-GM produced by initial patient CD34+ DR- cells was decreased
      compared to normal, whereas these values were similar to normal for CD34+ DR+
      cells. BFU-E, HPP-CFC and LTC-IC were reduced for both patient CD34+ DR- and
      CD34+ DR+ subpopulations. In contrast to normal, the patient CD34+ DR- fraction
      was not enriched in LTC-IC. CFU-GM expansion from patient CD34+ DR- cells was
      poor and decreased after 14 d of culture. No HPP-CFC expansion could be observed
      for patient cells. LTC-IC were below the level of detection after 14-21 d of
      expansion culture of CD34+ DR- patient cells, whereas they were variably
      maintained or expanded for normal cells. After expansion culture, cytogenetic
      and/or FISH analyses did not reveal the anomalies present at diagnosis,
      regardless of the cell subpopulation analysed. In conclusion, BM cells of
      patients with AML in CR show a profound defect at the level of a stem cell
      enriched population. No meaningful ex vivo expansion could be obtained in culture
      conditions allowing for a significant expansion from a normal stem cell
      population.

PMID- 9633905
TI  - The dose of granulocyte colony-stimulating factor administered following
      cytotoxic chemotherapy is not related to the rebound level of circulating CD34+
      haemopoietic progenitor cells during marrow recovery.
AB  - We report on the RmetHuG-CSF (filgrastim)-related mobilization efficiency in 120
      patients with multiple myeloma who received cytotoxic chemotherapy. Three
      schedules of G-CSF administration starting 24h after the end of chemotherapy were
      used: (1) a standard dose of 300 microg/d until the completion of PBSC
      collection; (2) dose escalation from 300 to 600-1200 microg/d during marrow
      recovery; (3) 600 or 1200 microg/d starting 24 h after cytotoxic chemotherapy. As
      a result, the individual dose per kg bodyweight varied between 2.83 and 23.08
      microg. No relationship was found between the dose of G-CSF administered and the
      peak level of circulating CD34+ cells or the CD34+ cell counts recorded over the
      entire collection period.

PMID- 9633906
TI  - Mutation analysis by a non-radioactive single-strand conformation polymorphism
      assay in nine families with X-linked severe combined immunodeficiency (SCIDX1).
AB  - X-linked severe combined immunodeficiency (SCIDX1) is an inherited disease
      characterized by profound abnormalities of cell-mediated and humoral immunity.
      Patients with SCIDX1 have defects in the common cytokine receptor gamma chain
      gene (IL2RG) that encodes a shared, essential component of the receptors for
      interleukin-2 (IL-2), IL-4, IL-7, IL-9 and IL-15. We have characterized nine
      SCIDX1 families by using a DNA-based, non-radioactive screening method and DNA
      sequencing. Nine different mutations were found, scattered from exon 1 to exon 5
      of the IL2RG gene. Two of these mutations have been previously identified in
      other unrelated patients; the other seven are novel mutations that differ from
      all of the 95 already reported in the IL2RG mutation data base. In addition to
      describing novel mutations in the IL2RG gene, this study shows that the knowledge
      of the genetic defect and the use of an efficient, non-radioactive, and rapid
      screening approach have important implications for prenatal and postnatal
      diagnosis, carrier female identification, and possibly prenatal therapy.

PMID- 9633907
TI  - Intravenous immunoglobulin therapy and renal dysfunction.

PMID- 9633908
TI  - Infectious complications after CD34-selected autologous peripheral blood stem
      cell transplantation.

PMID- 9633909
TI  - Screening for factor V Leiden and a prothrombin gene polymorphism in patients
      with Glanzmann's thrombasthenia.

PMID- 9633910
TI  - G-CSF after PBSC transplantation.

PMID- 9633911
TI  - Methotrexate therapy to alleviate anaemia in a patient with large granular
      lymphocytosis.

PMID- 9633912
TI  - Apoptosis: basic mechanisms and implications for cardiovascular disease.

PMID- 9633913
TI  - Role of apoptosis in the disappearance of infiltrated and proliferated
      interstitial cells after myocardial infarction.
AB  - Myocardial infarction (MI) progresses from the acute death of myocytes and the
      infiltration of inflammatory cells into granulation, followed by scars. During
      the healing process, the myocardial interstitial cell population in the infarcted
      tissues increases markedly and then decreases. We postulated that apoptosis is
      responsible for this process. Twenty-four male Japanese white rabbits underwent a
      30-minute occlusion of the left coronary artery followed by reperfusion for 2
      days, 2 weeks, or 4 weeks (n=8 each). The histological features consisted of dead
      cardiomyocytes and marked leukocyte infiltration at 2 days after MI and
      granulation consisting of numerous alpha-smooth muscle actin-positive
      myofibroblasts, macrophage antigen-positive macrophages, and neovascularization
      at 2 weeks. At 4 weeks, the cellularity decreased markedly, and scars were
      evident. Interstitial cells with positive nick end labeling were significantly
      more frequent at the light microscopic level in the 2-day MI samples (5.3+/-3.6%
      in the center and 6.9+/-3.3% in the periphery of the infarct region) than in the
      2-week (2.5+/-1.0%) and 4-week (0.5+/-0.5%) samples. DNA electrophoresis showed a
      clear ladder in tissues from the ischemic areas at 2 days after MI but not at 2
      and 4 weeks after MI. Ultrastructurally, typical apoptotic figures, including
      apoptotic bodies and condensed nuclei without ruptured plasma membranes, were
      detected in leukocytes from all hearts with 2-day MI and in myofibroblasts,
      endothelial cells, and macrophages from all hearts with 2-week MI. In the
      electron microscopic in situ nick end labeling, immunogold particles intensely
      labeled the condensed chromatin of the typical apoptotic nuclei. These particles
      were also accumulated on nuclei of the interstitial cells showing homogeneous
      density but not definite condensation as typical apoptotic nuclei, suggesting an
      early stage of apoptosis. Thus, apoptosis plays an important role in the
      disappearance of both the infiltrated leukocytes and the proliferated
      interstitial cells after MI. This finding may have therapeutic implications for
      postinfarct ventricular remodeling through apoptosis handling during the healing
      stage of MI.

PMID- 9633914
TI  - Effect of vacuolar proton ATPase on pHi, Ca2+, and apoptosis in neonatal
      cardiomyocytes during metabolic inhibition/recovery.
AB  - Recently, we found that vacuolar proton ATPase (VPATPase) operates in
      cardiomyocytes as a complementary proton-extruding mechanism. Its activity was
      increased by preconditioning with resultant attenuation of intracellular
      acidification during ischemia. In this study, we examined whether VPATPase
      mediated proton efflux during metabolic inhibition/recovery may spare Na+
      overload via Na+-H+ exchange, attenuate Na+-Ca2+ exchange, and decrease
      apoptosis. Neonatal rat cardiomyocytes were subjected to 2- to 3-hour metabolic
      inhibition with cyanide and 2-deoxyglucose and 24-hour recovery. The effect of
      VPATPase inhibition by 50 nmol/L bafilomycin A1 on apoptosis, pHi, and [Ca2+]i
      was studied by flow cytometry with propidium iodide, seminaphthorhodafluor
      (SNARF)-1-AM, and indo-1-AM staining, respectively. VPATPase inhibition increased
      the amount of apoptosis measured after 24 hours of recovery and abrogated the
      protective effect of inhibition of Na+-H+ exchange by (5-N-ethyl-N
      isopropyl)amiloride (EIPA). Dual blockade of VPATPase and Na+-H+ exchange was
      additive in effect with EIPA on pHi during metabolic inhibition/recovery and
      recovery from the acid challenge with sodium propionate. VPATPase blockade
      increased the rate of accumulation of intracellular Ca2+ at the beginning of
      metabolic inhibition and abrogated the delaying effect of EIPA on intracellular
      Ca2+ accumulation. These results indicate that VPATPase plays an important
      accessory role in cardiomyocyte protection by reducing acidosis and Na+-H+
      exchange-induced Ca2+ overload.

PMID- 9633915
TI  - Angiotensin II stimulation in vitro induces hypertrophy of normal and
      postinfarcted ventricular myocytes.
AB  - To determine whether angiotensin II (Ang II) stimulation of adult ventricular
      myocytes in vitro results in cellular hypertrophy, the changes in myocyte volume
      and protein content per cell were examined by confocal microscopy. Moreover, the
      possibility was considered that the upregulation of Ang II receptors on myocytes
      after infarction may potentiate and/or accelerate Ang II-mediated myocyte growth.
      Left ventricular myocytes isolated from control and failing hearts 3 days after
      infarction were cultured for 3 and 7 days in the presence of Ang II. Normal
      myocytes did not show an increase in volume and protein content at 3 days, but a
      16% and 20% increase in these respective parameters was found at 7 days. Cell
      growth was faster and greater in myocytes from postinfarcted hearts. In these
      cells, myocyte volume increased 23% and protein content increased 28% at 3 days
      after Ang II administration. The higher hypertrophic reaction of myocytes from
      infarcted hearts occurred in spite of a 19% larger volume at isolation. In both
      groups of myocytes, the AT1 receptor blocker losartan completely inhibited the
      consequences of Ang II. Conversely, the AT2 receptor antagonist PD123319 had no
      effect on Ang II-induced hypertrophy. In conclusion, Ang II promotes myocyte
      growth through the activation of AT1 receptors, which modulate the time and
      magnitude of this cellular response.

PMID- 9633916
TI  - Beta1 integrins participate in the hypertrophic response of rat ventricular
      myocytes.
AB  - Multiple signaling pathways have been implicated in the hypertrophic response of
      ventricular myocytes, yet the importance of cell-matrix interactions has not been
      extensively examined. Integrins are cell-surface molecules that link the
      extracellular matrix to the cellular cytoskeleton. They can function as cell
      signaling molecules and transducers of mechanical information in noncardiac
      cells. Given these properties and their abundance in cardiac cells, we evaluated
      the hypothesis that beta1 integrin function is involved in the alpha1-adrenergic
      mediated hypertrophic response of neonatal rat ventricular myocytes. The
      hypertrophic response of this model required interaction with extracellular
      matrix proteins. Specificity of these results was confirmed by demonstrating that
      ventricular myocytes plated onto an anti-beta1 integrin antibody supported the
      hypertrophic gene response. Adenovirus-mediated overexpression of beta1 integrin
      augmented the myocyte hypertrophic response when assessed by protein synthesis
      and atrial natriuretic factor production, a marker gene of hypertrophic
      induction. DNA synthesis was not altered by integrin overexpression. Transfection
      of cultured cardiac myocytes with either the ubiquitously expressed beta1A
      integrin or the cardiac/skeletal muscle-specific beta1 isoform (beta1D) activated
      reporter expression from both the atrial natriuretic factor and myosin light
      chain-2 ventricular promoters, genetic markers of ventricular cell hypertrophy.
      Finally, suppression of integrin signaling by overexpression of free beta1
      integrin cytoplasmic domains inhibited the adrenergically mediated atrial
      natriuretic factor response. These findings show that integrin ligation and
      signaling are involved in the cardiac hypertrophic response pathway.

PMID- 9633917
TI  - Increased protein kinase C activity in myotrophin-induced myocyte growth.
AB  - Myotrophin, a novel protein that has been shown to stimulate myocyte growth, has
      been isolated, purified, and sequenced from the hearts of spontaneously
      hypertensive rats and dilated cardiomyopathic human tissue. Recently, the cDNA
      clones encoding myotrophin have been isolated and expressed in Escherichia coli,
      and the recombinant myotrophin was found to be as biologically and
      immunologically active as natural myotrophin. The mechanism by which myotrophin
      stimulates protein synthesis and initiates myocardial hypertrophy is not known.
      To evaluate the involvement of protein kinase C (PKC) in myotrophin-induced
      hypertrophy, PKC activity and its distribution in the subcellular fraction were
      determined in cultured neonatal and adult myocytes. PKC activity was determined
      by measuring the incorporation of 32P into histone type III-S and PKCepsilon
      substrate peptide (epsilon(pep)) from [gamma-32P]ATP in neonatal myocytes.
      Myotrophin significantly stimulated PKC activity in neonatal myocytes and was
      associated with a significant increase in protein synthesis. The effect of
      myotrophin on the stimulation of PKC activity and [3H]leucine incorporation was
      abolished by pretreatment with either staurosporine or H-7, two selective,
      pharmacological PKC inhibitors. Pretreatment of myocytes with staurosporine also
      reduced the myotrophin-induced mRNA levels of c-fos and beta-myosin heavy chain.
      To evaluate the subcellular events whose occurrence was due to myotrophin and
      translocation of PKC, we studied the effect of genistein, a tyrosine kinase
      inhibitor, on myotrophin-induced neonatal myocyte growth. Genistein attenuated
      the [3H]leucine incorporation induced by myotrophin. To define the specificity of
      the PKC isoform(s) involved in myotrophin-stimulated myocyte growth, both
      neonatal and adult myocytes were treated with myotrophin, and Western blot
      analyses were performed by using the antibodies of different PKC isoforms.
      Results showed that both PKCalpha and PKCepsilon isoforms participated in the
      myotrophin-induced neonatal myocyte growth, whereas only the PKCepsilon isoform
      was involved in myotrophin-induced adult myocyte hypertrophy. PKCdelta and
      PKCzeta do not seem to participate in either neonatal or adult myocyte growth
      induced by myotrophin. Treatment with antisense oligonucleotides specific for
      PKCalpha and PKCepsilon isoforms further supported this result. PKCalpha is the
      major PKC isoform in neonatal myocytes and needs Ca2+ and phospholipids for its
      activation, and PKCepsilon (the Ca2+-independent PKC isoform) is present in both
      neonatal and adult myocytes; the 15-mer antisense oligodeoxynucleotides of each
      were used for this study. Treatment of neonatal myocytes with the PKCalpha and
      PKCepsilon antisense oligodeoxynucleotides for 5 days significantly reduced Ca2+
      dependent and Ca2+-independent PKC activity, respectively, as well as the
      [3H]leucine incorporation induced by myotrophin. Furthermore, myotrophin-induced
      PKC activity was primarily located in the particulate fraction and did not result
      in a concomitant decrease in the cytosolic fraction. Myotrophin does not change
      PKC isoform expression (both Ca2+ dependent and independent PKC isoforms used in
      this study) in rat neonatal cardiac fibroblasts. Our data suggest that myotrophin
      exerts its action on protein synthesis, possibly through a tyrosine kinase
      coupled pathway and translocation of PKC from the cytosol to the cell membrane.

PMID- 9633918
TI  - Regulation of mitochondrial [NADH] by cytosolic [Ca2+] and work in trabeculae
      from hypertrophic and normal rat hearts.
AB  - Pressure overload hypertrophy has previously been shown to reduce contractility
      but paradoxically to increase O2 consumption rates at a given force. Because O2
      consumption rates are related to mitochondrial [NADH] ([NADH]m), we tested the
      hypothesis that with hypertrophy, control of [NADH]m may be altered. Left
      ventricular trabeculae were isolated from banded and control rat hearts, and
      fluorescence spectroscopy was used to monitor [NADH]m and cytosolic [Ca2+]
      ([Ca2+]c). The hearts from banded rats developed hypertrophy (heart-to-body
      weight ratio increased from 4.1+/-0.1 to 4.9+/-0.1 mg/g) and hypertension
      (systolic arterial pressure increased from 117+/-4 to 175+/-5 mm Hg). Muscle
      workload was increased by stepwise increases in pacing frequency (up to 2 Hz).
      After increased work, [NADH]m fell and then slowly recovered toward control
      levels. When work was decreased, [NADH]m overshot control values and then slowly
      returned. The Ca2+-independent initial fall was larger for trabeculae from rats
      with hypertrophied hearts than from control rats (eg, 17+/-2% versus 11+/-1% when
      work was increased by increasing the frequency from 0.25 to 1 Hz). At 1 Hz,
      average [Ca2+]c was approximately 280 nmol/L, and the Ca2+-dependent [NADH]m
      recovery was larger for trabeculae from rats with hypertrophied hearts (17+/-4%
      versus 10+/-2%) despite similar average [Ca2+]c. At steady state after Ca2+
      dependent recovery, there was no difference in [NADH]m (fall of 1+/-2% versus 1+/
      1%). Furthermore, the Ca2+-dependent overshoot was larger for trabeculae from
      hypertrophied than from control hearts (increase of 14+/-2% versus 9+/-2% when
      frequency was decreased from 1 to 0.25 Hz). We conclude that (1) there is
      initially a larger imbalance in NADH production versus consumption rate in
      hypertrophy (because NADH fell more) and (2) the Ca2+-dependent recovery
      mechanism is enhanced in hypertrophy (because NADH recovered and overshot more),
      thus compensating for the larger imbalance.

PMID- 9633919
TI  - Ineffective perfusion-contraction matching in conscious, chronically instrumented
      pigs with an extended period of coronary stenosis.
AB  - Several models purported to represent hibernating myocardium involve a coronary
      stenosis (CS) to reduce blood flow (BF) and function without eliciting necrosis
      in anesthetized pigs. The goal of the present study was to determine whether
      sustained moderate reduction in coronary BF in conscious pigs induced hibernating
      myocardium, ie, perfusion-contraction matching with no necrosis. These
      experiments were conducted in conscious pigs chronically instrumented with a
      coronary artery BF probe and hydraulic occluder, left ventricular (LV) pressure
      gauge, and wall thickening (WT) crystals in the potentially ischemic and
      nonischemic zones. The hydraulic occluder was inflated to induce a stable 41+/-4%
      reduction in BF for 24 hours. Ischemic zone systolic WT fell initially with CS
      and then continued to decline during the period of CS even though blood flow did
      not change further, suggesting the induction of myocardial stunning. At 2 days
      after release of CS, WT was still depressed by 48+/-15%. Assessment of necrosis
      by histology or triphenyltetrazolium chloride showed 40+/-5% multifocal patchy
      necrosis interspersed with normal tissue involving the inner one third to one
      half of the ventricular wall. Regional myocardial BF (radioactive microsphere
      technique) was assessed by dividing the entire LV into an average of 488+/-59
      pieces and examining the spatial distribution of BF within the area at risk
      (AAR). BF in the samples in the area of patchy necrosis was reduced (-66+/-4%
      from a baseline of 1.55+/-0.27 mL x min(-1) x g(-1)), whereas BF was maintained
      in samples in the AAR without necrosis (-2+/-7% from a baseline of 1.25+/-0.22 mL
      x min(-1) x g(-1)). These findings indicate that when hypoperfusion induced by CS
      in conscious pigs is sustained, the result is necrosis rather than hibernating
      myocardium. The remainder of the AAR, which lacked necrosis, might have been
      mistaken for hibernating myocardium had only histology been evaluated and BF not
      been measured and found to be at normal levels.

PMID- 9633920
TI  - Simulation study of cellular electric properties in heart failure.
AB  - Patients with severe heart failure are at high risk of sudden cardiac death. In
      the majority of these patients, sudden cardiac death is thought to be due to
      ventricular tachyarrhythmias. Alterations of the electric properties of single
      myocytes in heart failure may favor the occurrence of ventricular arrhythmias in
      these patients by inducing early or delayed afterdepolarizations. Mathematical
      models of the cellular action potential and its underlying ionic currents could
      help to elucidate possible arrhythmogenic mechanisms on a cellular level. In the
      present study, selected ionic currents based on human data are incorporated into
      a model of the ventricular action potential for the purpose of studying the
      cellular electrophysiological consequences of heart failure. Ionic currents that
      are not yet sufficiently characterized in human ventricular myocytes are adopted
      from the action potential model developed by Luo and Rudy (LR model). The main
      results obtained from this model are as follows: The action potential in
      ventricular myocytes from failing hearts is longer than in nonfailing control
      hearts. The major underlying mechanisms for this prolongation are the enhanced
      activity of the Na+-Ca2+ exchanger, the slowed diastolic decay of the [Ca2+]i
      transient, and the reduction of the inwardly rectifying K+ current and the Na+-K+
      pump current in myocytes of failing hearts. Furthermore, the fast and slow
      components of the delayed rectifier K+ current (I(Kr) and I(Ks), respectively)
      are of utmost importance in determining repolarization of the human ventricular
      action potential. In contrast, the influence of the transient outward K+ current
      on APD is only small in both cell groups. Inhibition of I(Kr) promotes the
      development of early afterdepolarizations in failing, but not nonfailing,
      myocytes. Furthermore, spontaneous Ca2+ release from the sarcoplasmic reticulum
      triggers a premature action potential only in failing myocytes. This model of the
      ventricular action potential and its alterations in heart failure is intended to
      serve as a tool for investigating the effects of therapeutic interventions on the
      electric excitability of the human ventricular myocardium.

PMID- 9633921
TI  - Complement gene expression by rabbit heart: upregulation by ischemia and
      reperfusion.
AB  - Activation of the complement system has been implicated in the pathogenesis of
      myocardial ischemia/reperfusion injury. It has always been assumed that liver is
      the primary source of complement components. In the present study, we used the
      reverse-transcriptase polymerase chain reaction technique to establish that the
      mRNAs for complement proteins C3 and C9 are expressed in rabbit heart. Rabbit
      liver, brain, spleen, and kidney were also shown to express C3 and C9 mRNAs. We
      used Western blotting to establish that these mRNAs in heart are translated into
      the corresponding proteins. We further established that dramatic upregulation of
      the mRNAs occurred in Langendorff-perfused isolated hearts subjected to ischemia
      and reperfusion. C3 mRNA was always expressed at higher levels than was C9 mRNA,
      but C9 mRNA showed greater upregulation under stress. Compared with levels in
      control hearts subjected to 5 minutes of normoxic perfusion, hearts subjected to
      0.5 hours of ischemia followed by 1 hour of reperfusion had a 4.72-fold increase
      in C3 mRNA and a 19.5-fold increase in C9 mRNA. By contrast, C3 mRNA in hearts
      subjected to 3.5 hours of normoxic perfusion showed no change, and those
      subjected to 3.5 hours of ischemia showed only a 1.72-fold increase, whereas C9
      mRNA levels increased by 5.17-fold after 3.5 hours of normoxic perfusion and 12.5
      fold after 3.5 hours of ischemia. The results of this study demonstrate for the
      first time that heart tissue is capable of expressing genes and proteins of the
      complement system, although it is not yet known which cell types are responsible.
      They further demonstrate that ischemia and reperfusion of the heart promotes a
      rapid upregulation of the mRNAs encoding the complement proteins C3 and C9 and
      that these abnormal levels considerably exceed those of normal liver. These
      observations are consistent with the hypothesis that local production of
      complement proteins may contribute significantly to the degree of ischemic injury
      to the myocardium and that complement expression is augmented by reperfusion.

PMID- 9633922
TI  - Myocyte cell death in the diseased heart.

PMID- 9633923
TI  - Development of compartmental models in stable-isotope experiments: application to
      lipid metabolism.
AB  - Kinetic experiments are of great importance in lipid research because they
      further the understanding of lipid metabolism in vivo and help to explain the
      physiopathology of lipid disorders in humans. At present, due to species
      specificity, no valid animal model can efficiently replace a study in humans to
      explore lipid metabolism, and the use of radioactive tracers is restricted in
      humans. Thus, stable-isotope tracer kinetic studies have become an important
      component of research programs to achieve in humans a quantitative understanding
      of the dynamics of metabolic processes in vivo. The aim of this review is to
      describe the practical aspects of compartmental model development in stable
      isotope experiments. The recent development of computer hardware and modeling
      software has dramatically facilitated the task of the modeler in his or her
      calculations. In the current review, we show that the model may be considered an
      integral component of the experimental design and that model development must
      obey strict rules to provide a rigorous solution. The main difficulties of model
      development in tracer experiments, such as experiment design, model
      identifiability, data expression, comparison of models, or tracer recycling, are
      presented with extensive references. We have paid particular attention to kinetic
      modeling in stable-isotope experiments because they have shown the greatest
      development in recent years.

PMID- 9633924
TI  - HDL3-mediated inhibition of thrombin-induced platelet aggregation and fibrinogen
      binding occurs via decreased production of phosphoinositide-derived second
      messengers 1,2-diacylglycerol and inositol 1,4,5-tris-phosphate.
AB  - We demonstrate that physiological concentrations of HDL3 inhibit the thrombin
      induced platelet fibrinogen binding and aggregation in a time- and concentration
      dependent fashion. The underlying mechanism includes HDL3-mediated inhibition of
      phosphatidylinositol 4,5-bis-phosphate turnover, 1,2-diacylglycerol and inositol
      1,4,5-tris-phosphate formation, and intracellular calcium mobilization. The
      inhibitory effects of HDL3 on inositol 1,4,5-tris-phosphate formation and
      intracellular calcium mobilization were abolished after covalent modification of
      HDL3 with dimethylsuberimidate. Furthermore, they could be blocked by calphostin
      C and bis-indolylmaleimide, 2 highly selective and structurally unrelated protein
      kinase C inhibitors. However, the inhibitory effects of HDL3 were not blocked by
      H89, a protein kinase A inhibitor. In addition, HDL3 failed to induce cAMP
      formation but stimulated the phosphorylation of the protein kinase C 40- to 47-kD
      major protein substrate. We observed a close temporal relationship between the
      HDL3-mediated inhibition of thrombin-induced inositol 1,4,5-tris-phosphate
      formation, intracellular calcium mobilization, and fibrinogen binding and the
      phosphorylation of the protein kinase C 40- to 47-kD major protein substrate.
      Taken together, these findings indicate that the HDL3-mediated inhibition of
      thrombin-induced fibrinogen binding and aggregation occurs via inhibition of
      phosphatidylinositol 4,5-bis-phosphate turnover and formation of 1,2
      diacylglycerol and inositol 1,4,5-tris-phosphate. Protein kinase C may be
      involved in this process.

PMID- 9633925
TI  - Relationship between plasma viscosity and the severity of coronary heart disease.
AB  - Several studies have indicated that plasma viscosity contributes to
      cardiovascular risk in men. So far, a significant relationship between plasma
      viscosity and the severity of coronary heart disease has not been found. Thus,
      the present study is the first to report on the relationship of plasma viscosity
      and the severity of coronary heart disease. In a collective of 1142 male
      myocardial infarction patients, plasma viscosity and additional laboratory
      parameters were determined. Atherosclerotic changes were quantified by coronary
      angiography. Patients were divided into groups without any, and with one to three
      stenosed vessels. We found a positive relationship between plasma viscosity and
      the severity of coronary heart disease, even after adjusting groups for age,
      fibrinogen, and use of diuretics. Mean plasma viscosity ranged from 1.141+/-0.035
      mPa s in patients without stenosed vessels to 1.162+/-0.044 mPa s in patients who
      had three coronary vessels with stenoses >50%. Differences between the groups
      were significant (P<0.001 to 0.05), with two exceptions: differences between
      patients without any and with one stenosed vessel, as well as between patients
      with one and two stenosed vessels, did not reach the significance level. On the
      whole, we can give further support to the hypothesis that cardiovascular risk
      factors and coronary heart disease may be linked by plasma viscosity.

PMID- 9633926
TI  - Sialic acid content of LDL in coronary artery disease: no evidence of
      desialylation in subjects with coronary stenosis and increased levels in subjects
      with extensive atherosclerosis and acute myocardial infarction: relation between
      desialylation and in vitro peroxidation.
AB  - We recently showed that sialic acid content of LDL was not a marker of early
      cardiovascular disease (Arterioscler Thromb Vasc Biol. 1995;15:334-339). Here, we
      investigated this parameter in patients with advanced coronary artery disease
      (CAD). We first examined 100 patients having undergone coronary angiography. The
      distribution of LDL sialic acid values was very similar in subjects with no
      coronary stenosis (31.3+/-3.7 nmol/mg LDL protein, mean+/-SD) and those with > or
      = 75% stenosis in at least one main coronary artery or > or = 50% stenosis in at
      least two main coronary arteries (32.1+/-5.5 nmol/mg LDL protein). In contrast,
      LDL sialic acid content was significantly increased in patients with both
      coronary stenosis and peripheral arterial atherosclerotic lesions compared with
      those with either no lesion or only one or the other type of lesion. We then
      examined LDL sialic acid content in 20 patients with acute myocardial infarction.
      LDL sialic acid content was significantly higher (35.9+/-3.2 nmol/mg LDL protein)
      than that in the CAD(-) control group. These data suggest that LDL sialic acid
      content increases with the extension of atherosclerosis and its progression to
      acute complications. To explain the discordance with Orekhov and coworkers
      (Atherosclerosis. 1991;86:153-161), who showed that LDL sialic acid content in
      patients with advanced CAD was lower than that in healthy subjects, we studied
      the time courses of sialic acid, TBARS, and vitamin E levels in LDL dialyzed in
      different experimental conditions. A continuous decrease in both sialic acid and
      vitamin E levels and an increase in TBARS levels were observed in LDL samples
      containing less than 1 mmol/L EDTA, the intensity and rapidity of which varied
      with the EDTA concentration in the buffer. Our data support the idea that
      desialylation may result from in vitro peroxidation of LDL.

PMID- 9633927
TI  - An animal model to study local oxidation of LDL and its biological effects in the
      arterial wall.
AB  - Oxidized LDL (oxLDL) is present in atherosclerotic lesions and is believed to
      play a key role in atherogenesis. Mainly on the basis of cell culture studies,
      oxLDL has been shown to produce many biological effects that influence the
      atherosclerotic process. To study LDL oxidation in vivo, we have established a
      model in which Sprague-Dawley rats are given a single injection of unmodified
      human LDL (> or = 4 mg/kg body weight). Within 6 hours, an accumulation of
      apolipoprotein B and epitopes present on oxLDL are detected in the arterial
      endothelium and media. The presence of oxLDL is associated with activation of the
      transcription factor nuclear factor-kappaB in the endothelium as well as
      endothelial expression of intercellular adhesion molecule-1. Injection of LDL
      enriched with the antioxidant probucol resulted in arterial accumulation of
      apolipoprotein B, but the expression of oxLDL-specific epitopes was reduced at 24
      hours. Thus, this simple model has the potential to analyze the mechanisms behind
      and biological effects of LDL oxidation in vivo.

PMID- 9633928
TI  - Cyclic stretch upregulates production of interleukin-8 and monocyte chemotactic
      and activating factor/monocyte chemoattractant protein-1 in human endothelial
      cells.
AB  - In vivo, vascular walls are exposed to mechanical stretch, which may promote
      atherogenesis. This study was designed to investigate the effect of mechanical
      stretch on the production and gene expression of cytokines in endothelial cells
      (ECs) of human umbilical veins. ECs were cultured on flexible silicone membranes
      and exposed to cyclic mechanical stretch. Although the secretion levels of
      interleukin (IL)-1beta, tumor necrosis factor-alpha, IL-6, granulocyte (G) 
      colony stimulating factor (CSF), G and macrophage (M) -CSF, and M-CSF were not
      affected by cyclic stretch over 24 hours, the levels of IL-8 and monocyte
      chemotactic and activating factor (MCAF)/monocyte chemoattractant protein-1 (MCP
      1) were significantly increased by cyclic stretch. Northern blot analysis
      indicated that the mRNA levels of IL-8 and MCAF/MCP-1 were upregulated by cyclic
      stretch as a function of its intensity. Cytochalasin D, which disrupts the actin
      cytoskeleton, abolished the stretch-induced gene expression of IL-8 and MCAF/MCP
      1. In contrast, neither inhibition of stretch-activated ion channels nor
      disruption of microtubules affected the induction of these chemokines by cyclic
      stretch. Northern blot analysis using enzyme inhibitors showed that phospholipase
      C, protein kinase C, and tyrosine kinase were involved in the stretch-induced
      gene expression of IL-8 and MCAF/MCP-1, whereas cAMP- or cGMP-dependent protein
      kinase was not. In conclusion, cyclic stretch enhanced the secretion and gene
      expression of IL-8 and MCAF/MCP-1 in a stretch-dependent fashion, and the
      integrity of the actin cytoskeleton and activities of phospholipase C, protein
      kinase C, and tyrosine kinase may be essential in the process of stretch-induced
      gene induction of IL-8 and MCAF/MCP-1.

PMID- 9633929
TI  - Norethindrone acetate enhances the antiatherogenic effect of 17beta-estradiol: a
      secondary prevention study of aortic atherosclerosis in ovariectomized
      cholesterol-fed rabbits.
AB  - The influence of progestogens in combination with 17beta-estradiol (E2) on
      cardiovascular disease remains controversial. This study investigated the effect
      of norethindrone acetate (NETA) combined with E2 on aortic atherosclerosis.
      Eighty mature female rabbits were ovariectomized, then fed a cholesterol-rich
      diet (240 mg/d) for 14 weeks to induce aortic atherosclerosis. They were
      randomized to four equally large groups for the following 38-week intervention
      period. One group received placebo, another group oral E2 4 mg daily (E2), and
      the last two groups oral E2 4 mg daily combined with either NETA 1 mg (E2NETA1)
      or NETA 3 mg (E2NETA3). The cholesterol intake was reduced to a "maintenance"
      level of 80 mg/d during the intervention period. Total serum cholesterol and
      ultracentrifuged lipoproteins were analyzed enzymatically throughout the study.
      The cholesterol content in the aortic wall was 2.76+/-0.44 micromol/cm2 (mean+/
      SEM) in the E2NETA1 group, 1.77+/-0.37 micromol/cm2 in the E2NETA3 group, 5.46+/
      0.77 micromol/cm2 in the E2 group, and 7.20+/-0.94 micromol/cm2 in the placebo
      group (ANOVA P<0.0001). The difference (in the aortic cholesterol accumulation)
      between the E2 and each of the combined E2/NETA groups was statistically
      significant (P<0.01) but could only partly be explained by the differences in
      serum lipids and lipoproteins. In conclusion, NETA enhances the antiatherogenic
      effect of E2 in cholesterol-fed rabbits. This effect is only partially mediated
      through changes in serum lipids and lipoproteins.

PMID- 9633930
TI  - Inhibition of repetitive thrombus formation in the stenosed canine coronary
      artery by enoxaparin, but not by unfractionated heparin.
AB  - Experiments were designed to compare the antithrombotic efficacy of enoxaparin
      and unfractionated heparin (UH) in a model of platelet-dependent cyclic flow
      reductions (CFRs) in the stenosed canine circumflex coronary artery. Low
      molecular-weight heparins (LMWHs) are safe and effective in the prevention and
      treatment of venous thromboembolism. The present experiments were designed to
      evaluate the potential use of LMWHs in arterial thrombotic indications by
      comparing the antithrombotic effect of an LMWH with that of UH in an animal model
      of unstable angina. After establishment of consistent CFRs by experimentally
      induced vascular stenosis and damage, vehicle (saline), enoxaparin, or UH was
      administered intravenously as a loading dose plus a continuous infusion for 1
      hour. The inhibition of CFRs was taken as an indicator of antithrombotic
      efficacy. Enoxaparin inhibited repetitive platelet thrombus formation in a dose
      dependent manner, with significant inhibition of CFRs achieved at 0.5 mg/kg + 5
      microg/kg per minute. This dose of enoxaparin resulted in anti-Xa levels of 0.9
      to 1.0 IU/mL, anti-IIa levels of 0.2 to 0.3 IU/mL, activated partial
      thromboplastin time (APTT) of 1.3-fold over baseline, and a 1.4-fold increase
      (NS) in template bleeding time. Near-complete abolishment of CFRs was achieved
      with enoxaparin at 1.0 mg/kg + 10 microg/kg per minute. This dose of enoxaparin
      produced anti-Xa levels of 2 to 2.2 IU/mL, anti-IIa levels of 0.5 to 0.6 IU/mL,
      an increase in APTT of 1.4- to 1.5-fold over baseline, and a 1.9-fold increase
      (P<0.05) in template bleeding time. In contrast, UH had no significant effect on
      CFRs at a dose (100 U/kg + 10 U/kg per minute) that resulted in anti-Xa levels of
      1.2 to 1.6 IU/mL, anti-IIa levels of 1.8 to 2.4 IU/mL, an increase in APTT
      greater than 10-fold over baseline, and a 2.5-fold increase (P<0.05) in template
      bleeding time. Compared with the vehicle group, circulating platelet count and
      hematocrit were not changed significantly by any dose of enoxaparin or UH tested.
      Enoxaparin, unlike UH, prevented repetitive platelet-dependent thrombus formation
      in the dog, thereby supporting the potential use of enoxaparin as a replacement
      for heparin in the treatment of arterial thrombotic disorders such as unstable
      angina.

PMID- 9633931
TI  - Role of polymorphonuclear leukocytes in collar-induced intimal thickening in the
      rabbit carotid artery.
AB  - In this study, the involvement of polymorphonuclear leukocytes (PMNs) in the
      development of intimal thickening was investigated. A fibromuscular intima was
      induced by placing a silicone collar around the rabbit carotid artery for 3 days
      or 2 weeks; the contralateral artery was sham operated. Rabbits received placebo
      treatments (groups 1 and 3), granulocyte-colony stimulating factor (group 2; G
      CSF, 20 microg x kg(-1) x d(-1), delivered by subcutaneous osmotic pumps), or an
      anti-CD18 monoclonal antibody (group 4; 1.5 mg/kg i.v.). The G-CSF treatment
      raised the peripheral PMN count 5- to 12-fold but had no effect on intimal
      thickening on day 3, 12, or 14. A single injection of anti-CD18 prevented PMN
      extravasation 6 hours after collar implantation without influencing intimal
      hyperplasia on day 14. Repeated daily administration of anti-CD18 strongly bound
      to CD18 on peripheral PMNs and inhibited both PMN-dependent plasma extravasation
      in the skin and accumulation of CD14-immunoreactive leukocytes in the intima and
      media. However, anti-CD18 did not suppress early intimal thickening or
      accumulation of alpha-smooth muscle actin-immunoreactive cells by day 3. It thus
      appears that the PMN influx in the intima and media evoked by the perivascular
      collar is of little functional relevance to the subsequent smooth muscle cell
      migration and intimal thickening in this model.

PMID- 9633932
TI  - Intraluminal pressure is essential for the maintenance of smooth muscle caldesmon
      and filamin content in aortic organ culture.
AB  - Different forms of mechanical stimulation are among the physiological factors
      constantly acting on the vessel wall. We previously demonstrated that subjecting
      vascular smooth muscle cells (VSMCs) in culture to cyclic stretch increased the
      expression of high-molecular-weight caldesmon, a marker protein of a
      differentiated, contractile, VSMC phenotype. In the present work the effects of
      mechanical factors, in the form of circumferential stress and shear stress, on
      the characteristics of SM contractile phenotype were studied in an organ culture
      of rabbit aorta. Application of an intralumininal pressure of 80 mm Hg to aortic
      segments cultured in Dulbecco's modified Eagle's medium containing 20% fetal calf
      serum for 3 days prevented the decrease in high-molecular-weight caldesmon
      content (70+/-4% of initial level in nonpressurized vessel, 116+/-17% at 80 mm
      Hg) and filamin content (80+/-5% in nonpressurized vessel, 100+/-2% at 80 mm Hg).
      SM myosin and low-molecular-weight caldesmon contents showed no dependence on
      vessel pressurization. Neither endothelial denudation nor alteration of
      intraluminal flow rates affected marker protein content in 3-day vessel culture,
      thus excluding the possibility of any shear or endothelial effects. Maintenance
      of high high-molecular-weight caldesmon and filamin levels in the organ cultures
      of pressurized and stretched vessels demonstrates the positive role of mechanical
      factors in the control of the VSMC differentiated phenotype.

PMID- 9633933
TI  - Hyperleptinemia as a component of a metabolic syndrome of cardiovascular risk.
AB  - In humans, production of the adipocyte-derived peptide leptin has been linked to
      adiposity, insulin, and insulin sensitivity. We therefore considered that
      alterations in plasma leptin concentrations could constitute an additional
      component of a metabolic syndrome of cardiovascular risk. To explore this
      hypothesis, we employed factor analysis, a multivariate statistical technique
      that allows reduction of large numbers of highly intercorrelated variables to
      composite, biologically meaningful factors. Seventy-four men [age, 48.4+/-1.3
      years (mean+/-SEM); body mass index (BMI), 25.6+/-0.3 kg/m2] who were free of
      coronary heart disease and diabetes underwent anthropometric measurements
      (subscapular-to-triceps [S:T] and subscapular-to-biceps [S:B] skinfold thickness
      ratios, measurement of fasting plasma leptin, and an intravenous glucose
      tolerance test (IVGTT) for assessment of insulin sensitivity. Plasma leptin
      concentrations were correlated with BMI (r=0.57, P<0.001), S:T (r=0.34, P=0.003),
      S:B (r=0.37, P<0.001), systolic and diastolic blood pressures (both r=0.24,
      P=0.044), fasting triglycerides (r=0.31, P=0.007), serum uric acid (r=0.35,
      P=0.003), fasting glucose (r=0.32, P=0.003) and insulin (r=0.33, P=0.004), and
      IVGTT insulin (r=0.63, P<0.001). A negative correlation was observed between
      leptin and insulin sensitivity (r=-0.32, P=0.006). No significant correlations
      emerged between plasma leptin concentrations and age, high density lipoprotein
      cholesterol, or IVGTT glucose. In multivariate regression analyses, BMI
      (standardized coefficient [SC]=0.40, P=0.001), fasting insulin (SC=0.23,
      P=0.036), and IVGTT insulin (SC=0.51, P<0.001) emerged as independent predictors
      of plasma leptin concentrations (R2=0.56, P<0.001). After adjustment for BMI,
      only IVGTT insulin emerged as a significant predictor of plasma leptin
      concentrations (SC=0.56, P<0.001, R2=0.45, P<0.001). Factor analysis of plasma
      leptin concentrations and the variables that are considered relevant to the
      insulin resistance syndrome revealed a clustering of plasma leptin concentrations
      with a factor dominated by insulin resistance and high IVGTT insulin, separate
      from a high IVGTT glucose/central obesity factor and a high triglyceride/low high
      density lipoprotein cholesterol factor. Together, these factors accounted for
      55.9% of the total variance in the dataset. In conclusion, interindividual
      variations in plasma leptin concentrations are strongly related to the principal
      components of the insulin resistance syndrome. Further studies are needed to
      determine whether the insulin-leptin axis plays a coordinating role in this
      syndrome and whether plasma leptin concentrations could provide an additional
      measure of cardiovascular risk.

PMID- 9633934
TI  - IL-1beta-induced monocyte chemoattractant protein-1 gene expression in
      endothelial cells is blocked by proteasome inhibitors.
AB  - Human monocyte chemoattractant protein-1 (MCP-1) is expressed by a variety of
      cell types in response to various stimuli. MCP-1 expressed by the endothelium
      plays an important role in cell migration and activation. MCP-1 is a major
      chemoattractant for monocytes, T lymphocytes, and basophils. In the present
      study, we present evidence that the proteasome complex is involved in mediating
      the interleukin (IL)-1beta induction of MCP-1 in endothelial cells. We present
      evidence that a proteasome inhibitor, N-acetyl-leucinyl-leucinyl-norleucinal
      (norLeu), and the protease inhibitor tosyl-Phe-chloromethylketone (TPCK) block IL
      1beta induction of MCP-1 protein expression. norLeu and TPCK also blocked IL
      1beta-induced MCP-1 promoter-driven reporter gene expression as well as nuclear
      factor (NF)-kappaB-mediated reporter gene expression. The effects of norLeu were
      due to its inhibition of the proteasome rather than calpain, because other
      calpain inhibitors had no effect on MCP-1 expression. In contrast to TPCK, which
      blocked NF-kappaB translocation to the nucleus, norLeu had no effect on NF-kappaB
      nuclear translocation or IL-1beta-induced phosphorylation of p65. This study
      demonstrates that the proteasome pathway is involved in IL-1beta-induced MCP-1
      gene expression in human endothelial cells.

PMID- 9633935
TI  - Clinical features associated with the homozygous Trp64Arg mutation of the beta3
      adrenergic receptor: no evidence for its association with obesity in Japanese.
AB  - To characterize the clinical features associated with the Trp64Arg mutation of
      the beta3-adrenergic receptor (beta3-AR), the effects of this mutation, in
      particular the homozygous state (Arg/Arg), on obesity, blood pressure, and plasma
      lipoproteins were investigated in 2 populations: subjects residing on a small
      isolated island (group 1; n=746) and patients residing in Tokyo who attend a
      clinic for metabolic diseases (group 2; n=371). The allelic frequency of the
      Trp64Arg mutation was 23.4% in group 1 and 18.3% in group 2. No significant
      difference in the body mass index was observed between subjects with 3 different
      genotypes in each group. There was a trend that the Arg/Arg had higher systolic
      blood pressure than the Trp/Trp in both groups, but the differences were not
      statistically significant. The plasma LDL cholesterol levels were significantly
      lower in Arg/Arg than in Trp/Trp in men from the group 1 cohort (2.82+/-0.84
      versus 3.19+/-0.7 mmol/L, P<0.05). These results suggest that the homozygous
      Trp64Arg mutation is not a major contributing factor for obesity, but potentially
      contributed to higher systolic blood pressure and low plasma levels of LDL
      cholesterol in Japanese men.

PMID- 9633936
TI  - Interaction of diabetes and hypertension on determinants of endothelial
      adhesiveness.
AB  - Epidemiological studies have established that diabetes mellitus and hypertension
      are independent risk factors for atherosclerosis. One of the earliest
      abnormalities seen in atherogenesis is enhanced monocyte adherence to the
      endothelium. The mechanisms by which diabetes mellitus or hypertension enhances
      monocyte-endothelial cell interactions are incompletely characterized. It is not
      known whether there are additive interactions between these risk factors on
      endothelial adhesiveness for monocytes. Male Wistar-Kyoto (WKY) and spontaneously
      hypertensive (SHR) rats were fed a normal or fructose-enriched diet. In some
      cases, animals were injected with streptozotocin (35 mg/kg body weight) to induce
      diabetes. After 2 weeks, plasma was drawn for biochemical measurements, and
      thoracic aortas were harvested, opened longitudinally, and exposed to
      fluorescently labeled mouse monocytoid cells (WEHI 78/24, 2 x 10(6)/mL) for 30
      minutes on a rocking platform. Adherent cells were counted by epifluorescence
      microscopy. WEHI 78/24 binding to aortic segments from SHR animals was elevated
      compared with segments from WKYs. Fructose feeding alone had no effect on
      endothelial adhesiveness. When WKYs were made hyperglycemic by STZ injection,
      monocyte binding was 160% of the control value. Elevated monocyte binding was
      also observed in aortas derived from SHR animals injected with STZ, indicating an
      additive effect of hypertension and hyperglycemia. To determine whether
      alterations in oxidative state played a role in the endothelial adhesiveness,
      aortic segments were exposed to lucigenin (250 micromol/L) for measurement of
      superoxide anion. Aortic segments from SHR elaborated 120% more superoxide anion
      than did controls. Elevated free-radical production was also observed in aortas
      from diabetic WKYs. Furthermore, thoracic aortas derived from diabetic SHR
      animals elaborated more superoxide anion than did any of the other groups (374%,
      P<0.05). Immunohistochemical staining for monocyte chemotactic protein-1
      demonstrated increased expression in aortas isolated from diabetic WKY and SHR
      compared with control vessels. These studies demonstrate that both diabetes and
      hypertension lead to increased monocyte adherence to the endothelium. This
      abnormality is associated with increased vascular superoxide production and
      monocyte chemotactic protein-1 expression. Furthermore, there appears to be an
      additive interaction between hyperglycemia and hypertension in their effects on
      endothelial adhesiveness and its determinants.

PMID- 9633937
TI  - In vivo efficacy of SM-20302, a GP IIb/IIIa receptor antagonist, correlates with
      ex vivo platelet inhibition in heparinized blood but not in citrated blood.
AB  - We tested the hypothesis that the in vivo antithrombotic efficacy of SM-20302, a
      GP IIb/IIIa receptor antagonist, correlates with the ex vivo platelet inhibition
      in heparinized platelet rich plasma (hPRP) but not in citrated PRP (cPRP). The
      studies were performed in a canine model of carotid artery thrombosis in which
      thrombus formation was induced by electrolytic injury. Thrombosis of the right
      carotid artery was induced immediately after the administration of saline (n=12).
      Thirty minutes after persistent occlusive thrombosis was obtained, the vessel
      segment was ligated, and the time to occlusion and thrombus weight were noted.
      Subsequently, thrombosis of the left carotid artery was initiated in the presence
      of SM-20302 (100, 300, 600, or 1000 microg/kg i.v.; n=4 to 6). All the doses of
      SM-20302 inhibited (by > or = 90%) the ex vivo platelet aggregation induced by
      ADP and arachidonic acid (AA) in cPRP. In hPRP, a dose-dependent inhibition of ex
      vivo platelet aggregation was observed. The maximal inhibition produced by 100 to
      1000 microg/kg SM-20302 ranged from 18% to 80% for ADP and 44% to 88% for AA.
      Maximal prolongation of the template bleeding time induced by the 100-, 300-, 600
      , and 1000-microg/kg doses were 2.5-, 9.5-, 10-, and > 10-fold, respectively. All
      the injured carotid arteries (n=12) in the saline-treated group occluded. SM
      20302 pretreatment produced a dose-dependent maintenance of the carotid artery
      patency, and the incidence of occlusion at 4 hours was 5/6, 3/6, 0/6, and 0/6 for
      the 100-, 300-, 600-, and 1000-microg/kg doses, respectively. The results
      indicate that SM-20302 prevents carotid artery thrombosis in response to
      electrolytic arterial wall injury and that its in vivo antithrombotic efficacy
      can be correlated accurately with the ex vivo platelet inhibition in PRP prepared
      from heparinized blood but not from citrated blood.

PMID- 9633938
TI  - Effect of 17beta-estradiol on inhibition of platelet aggregation in vitro is
      mediated by an increase in NO synthesis.
AB  - The low prevalence of coronary heart disease in premenopausal women and its
      increase after menopause are well established. Although estrogen is thought to
      play a role in protecting the vasculature, the mechanism has not been fully
      clarified. The contribution of platelets to atherosclerotic cardiovascular
      diseases is well recognized. The present study focused on the still-controversial
      effect of estrogen on platelet function. We investigated the in vitro effects of
      estrogen on human platelets, including their aggregation, Ca2+ metabolism, the
      synthesis of cyclic nucleotides, and NO (nitrite/nitrate) synthesis after
      stimulation with thrombin or ADP. Pretreatment of platelets with 17beta-estradiol
      reduced the platelet aggregation induced by thrombin or ADP, whereas 17alpha
      estradiol had no effect. 17Beta-estradiol accelerated the recovery of [Ca2+]i
      after the agonist-induced peak and reduced the area under the curve of
      accumulated platelet [Ca2+]i but did not alter the baseline [Ca2+]i, Ca2+ influx
      induced by thrombin or ADP, the release of Ca2+ from internal stores, or the size
      of internal Ca2+ stores. Pretreatment of platelets with 17beta-estradiol had no
      effect on the intracellular concentration of cAMP but increased that of cGMP in
      agonist-stimulated platelets. Additionally, 17beta-estradiol increased the
      platelet concentration of nitrite/nitrate in a dose-dependent manner. These
      effects of 17beta-estradiol on platelet aggregation, Ca2+ metabolism, and NO
      synthesis were abolished by exposure to N(G)-monomethyl-L-arginine, an NO
      synthesis inhibitor. These results suggest that 17beta-estradiol plays an
      important role in inhibiting platelet aggregation by promoting Ca2+ extrusion or
      reuptake activity that is dependent on the production of cGMP by increasing NO
      synthesis.

PMID- 9633939
TI  - Apolipoprotein B-48 or its apolipoprotein B-100 equivalent mediates the binding
      of triglyceride-rich lipoproteins to their unique human monocyte-macrophage
      receptor.
AB  - Studies in animals and humans have demonstrated uptake of plasma chylomicrons
      (triglyceride-rich lipoprotein [TGRLP] of Sf>400) by accessible macrophages in
      vivo. One potential mechanism is via a unique receptor pathway we previously
      identified in human blood and THP-1 monocytes and macrophages for the lipoprotein
      lipase (LpL)- and apolipoprotein (apo) E-independent, high-affinity, specific
      binding of plasma chylomicrons and hypertriglyceridemic VLDL (HTG-VLDL) to cell
      surface membrane-binding proteins (MBP 200, 235; apparent Mr 200, 235 kD on SDS
      PAGE) that leads to lipid accumulation in vitro. Competitive binding studies
      reported here demonstrate that anti-apoB antibodies specifically block the high
      affinity binding of TGRLP to this receptor on THP-1 cells and on ligand blots.
      LpL, which binds to an N-terminal domain of apoB, also inhibits TGRLP binding
      both to this site on THP-1s and to MBP 200, 235 by binding to apoB. Chylomicrons
      of Sf>1100 that contain apoB-48, but not apoB-100, bind specifically to MBP 200,
      235, and this binding is blocked by anti-apoB IgG. In contrast, lactoferrin and
      heparin do not inhibit TGRLP binding. We conclude that the receptor-binding
      domain is within apoB-48 (or an equivalent in apoB-100) near the LpL-binding
      domain, but not a heparin-binding domain. Uptake of TGRLP by this mechanism could
      provide essential nutrients or, in HTG, cause excess lipid accumulation and foam
      cell formation.

PMID- 9633940
TI  - Oxidized cholesterol in the diet accelerates the development of aortic
      atherosclerosis in cholesterol-fed rabbits.
AB  - Oxidized lipoproteins may play a role in atherosclerosis. Recently, we have
      demonstrated that the levels of oxidized fatty acids in the circulation correlate
      directly with the quantity of oxidized fatty acids in the diet and that dietary
      oxidized fatty acids accelerate atherosclerosis in rabbits. The present study
      tests the hypothesis that oxidized cholesterol in the diet accelerates the
      development of atherosclerosis. Rabbits were fed a diet containing 0.33%
      nonoxidized cholesterol (control diet) or the same diet containing 0.33%
      cholesterol of which 5% was oxidized (oxidized diet). Serum cholesterol levels
      increased to a similar extent in both groups, with the majority of cholesterol in
      the beta-VLDL fraction. Moreover, in the serum beta-VLDL fraction and liver,
      there was a significant increase in the oxidized cholesterol levels. Most
      importantly, feeding a diet enriched in oxidized cholesterol resulted in a 100%
      increase in fatty streak lesions in the aorta. Western diets contain high
      concentrations of oxidized cholesterol products, and our results suggest that
      these foods may be a risk factor for atherosclerosis.

PMID- 9633941
TI  - Dominant negative effect of TGF-beta1 and TNF-alpha on basal and IL-6-induced
      lipoprotein(a) and apolipoprotein(a) mRNA expression in primary monkey hepatocyte
      cultures.
AB  - Lipoprotein(a) [Lp(a)] consists of apolipoprotein(a) [apo(a)] disulfide linked to
      apolipoprotein B-100 of LDL. Elevated plasma Lp(a) is an independent risk factor
      for a variety of vascular diseases. Lp(a) has been reported to be an acute-phase
      reactant, suggesting that cytokines may regulate its levels. To determine whether
      Lp(a) expression was subject to modulation by cytokines, primary monkey
      hepatocytes that endogenously express Lp(a) were used. Hepatocytes were treated
      with interleukin (IL)-6, the major mediator of the acute-phase response, and
      several other cytokines. IL-6 treatment (0.3 to 10 ng/mL) resulted in a marked,
      dose-dependent, 2- to 4-fold enhancement of Lp(a) accumulation in the hepatocyte
      culture media that was highly correlated with changes in apo(a) mRNA levels
      (r>0.9). Several other cytokines, such as IL-2, IL-8, and hepatocyte growth
      factor, had no significant effect on Lp(a) levels; however, transforming growth
      factor-beta1 (TGF-beta1) and tumor necrosis factor-alpha (TNF-alpha) were very
      active in inhibiting Lp(a) accumulation in the culture media, with IC50s of
      approximately 0.3 and 1 ng/mL, respectively. Both TGF-beta1 and TNF-alpha also
      decreased the apo(a) transcript. Mixing experiments, in which hepatocytes were
      treated with 10 ng/mL of IL-6 and 0.3 to 10 ng/mL of TGF-beta1 or TNF-alpha,
      demonstrated that the IL-6-mediated induction of Lp(a) and apo(a) mRNA was
      ablated with very low levels of either inhibitory cytokine, suggesting a dominant
      negative effect of TGF-beta1 and TNF-alpha. These results show that Lp(a) and
      apo(a) mRNA expression in primary monkey hepatocytes is subject to both positive
      (IL-6) and negative (TGF-beta1 and TNF-alpha) regulation by physiological levels
      of cytokines. Thus, in vivo Lp(a) levels may be dependent on the balance between
      stimulatory and inhibitory cytokines.

PMID- 9633942
TI  - Hormone-sensitive lipase overexpression increases cholesteryl ester hydrolysis in
      macrophage foam cells.
AB  - Atherosclerosis is a complex physiopathologic process initiated by the formation
      of cholesterol-rich lesions in the arterial wall. Macrophages play a crucial role
      in this process because they accumulate large amounts of cholesterol esters (CEs)
      to form the foam cells that initiate the formation of the lesion and participate
      actively in the development of the lesion. Therefore, prevention or reversal of
      CE accumulation in macrophage foam cells could result in protection from multiple
      pathological effects. In this report, we show that the CE hydrolysis catalyzed by
      neutral cholesterol ester hydrolase (nCEH) can be modulated by overexpression of
      hormone-sensitive lipase (HSL) in macrophage foam cells. For these studies, RAW
      264.7 cells, a murine macrophage cell line, were found to be a suitable model of
      foam cell formation. HSL expression and nCEH activity in these cells and in
      peritoneal macrophages were comparable. In addition, antibody titration showed
      that essentially all nCEH activity in murine macrophages was accounted for by
      HSL. To examine the effect of HSL overexpression on foam cell formation, RAW
      264.7 cells were stably transfected with a rat HSL cDNA. The resulting HSL
      overexpression increased hydrolysis of cellular CEs 2- to 3-fold in lipid-laden
      cells in the presence of an acyl coenzyme A:cholesterol acyltransferase (ACAT)
      inhibitor. Furthermore, addition of cAMP produced a 5-fold higher rate of CE
      hydrolysis in cholesterol-laden, HSL-overexpressing cells than in control cells
      and resulted in nearly complete hydrolysis of cellular CEs in only 9 hours,
      compared with <50% hydrolysis in control cells. Thus, HSL overexpression
      stimulated the net hydrolysis of CEs, leading to faster hydrolysis of lipid
      deposits in model foam cells. These data suggest that HSL overexpression in
      macrophages, alone or in combination with ACAT inhibitors, may constitute a
      useful therapeutic approach for impeding CE accumulation in macrophages in vivo.

PMID- 9633943
TI  - Estradiol stimulates apolipoprotein A-I- but not A-II-containing particle
      synthesis and secretion by stimulating mRNA transcription rate in Hep G2 cells.
AB  - Estrogen therapy increases plasma HDL levels, which may reduce cardiovascular
      risk in postmenopausal women. The mechanism of action of estrogen in influencing
      various steps in hepatic HDL and apolipoprotein (apo) A-I synthesis and secretion
      are not fully understood. In this study, we have used the human hepatoblastoma
      cell line (Hep G2) as an in vitro model system to delineate the effect of
      estradiol on multiple regulatory steps involved in hepatic HDL metabolism.
      Incubation of Hep G2 cells with estradiol resulted in the following statistically
      significant findings: (1) increased accumulation of apoA-I in the medium without
      affecting uptake/removal of radiolabeled HDL-protein; (2) accelerated
      incorporation of [3H]leucine into apoA-I; (3) selective increase in [3H]leucine
      incorporation into lipoprotein (LP) A-I but not LP A-I+A-II HDL particles (HDL
      particles without and with apoA-II, respectively); (4) increased ability of apoA
      I-containing particles to efflux cholesterol from fibroblasts; (5) stimulated
      steady state apoA-I but not apoA-II mRNA expression; and (6) increased newly
      transcribed apoA-I mRNA message without effect on apoA-I mRNA half-life. The data
      indicate that estradiol stimulates newly transcribed hepatic apoA-I mRNA,
      resulting in a selective increase in LP A-I, a subfraction of HDL that is
      associated with decreased atherosclerotic cardiovascular disease, especially in
      premenopausal women.

PMID- 9633944
TI  - Association of specific LDL receptor gene mutations with differential plasma
      lipoprotein response to simvastatin in young French Canadians with heterozygous
      familial hypercholesterolemia.
AB  - In familial hypercholesterolemia (FH), the efficacy of the inhibitors of 3
      hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase shows considerable
      interindividual variation, and several genetic and environmental factors can
      contribute to explaining this variability. A randomized, double-blind, placebo
      controlled clinical trial with simvastatin, an HMG-CoA reductase inhibitor, was
      conducted in 63 children and adolescents with heterozygous FH. The patients were
      grouped according to known LDL receptor genotype. After 6 weeks of treatment with
      20 mg/d simvastatin, the mean reduction in plasma LDL cholesterol in patients
      with the W66G mutation (n=14) was 31%, whereas in the deletion>15 kb (n=23) and
      the C646Y mutation groups (n=10), it was 38% and 42%, respectively (P<0.05).
      After treatment with simvastatin, HDL cholesterol levels were increased in all
      groups, and triglyceride concentrations were significantly reduced. Multiple
      regression analyses suggested that 42% of the variation of the LDL cholesterol
      response to simvastatin can be attributed to variation in the mutant LDL receptor
      locus, apolipoprotein E genotype, and body mass index, while 35% of the variation
      in HDL cholesterol response was explained by sex and baseline HDL cholesterol.
      These results show that simvastatin was an effective and well-tolerated therapy
      for FH in the pediatric population for all LDL receptor gene mutations. Moreover,
      the nature of LDL receptor gene mutations and other genetic and constitutional
      factors play a significant role in predicting the efficacy of simvastatin in the
      treatment of FH in children and adolescents.

PMID- 9633945
TI  - Low expression of the apolipoprotein B mRNA-editing transgene in mice reduces LDL
      levels but does not cause liver dysplasia or tumors.
AB  - Hepatic expression of apolipoprotein (apo) B mRNA-editing enzyme catalytic
      polypeptide 1 (APOBEC-1) has been proposed as a gene therapy approach for
      lowering plasma low density lipoprotein (LDL) levels. However, high-level
      expression of APOBEC-1 in transgenic mouse and rabbit livers causes liver
      dysplasia and hepatocellular carcinoma. To determine the physiological and
      pathological effects of low-level hepatic expression of APOBEC-1, we used a 52-kb
      rat APOBEC-1 genomic clone (RE4) to generate transgenic mice expressing low
      levels of APOBEC-1 (2 to 5 times those in nontransgenic mice). Liver function,
      liver histology, editing of apoB mRNA at the normal editing site (C6666), and
      abnormal editing at multiple sites (hyperediting) in these mice were compared
      with those in transgenic mice expressing intermediate (I-20) or high (I-28)
      levels of APOBEC-1 in the liver. Hyperediting of mRNA coding for the novel APOBEC
      1 target 1 (NAT1) was also examined. In the high-expressing I-28 line, 50% of the
      mice had palpable tumors at 15 weeks of age, whereas in the intermediate
      expressing I-20 line, 50% of the mice had evidence of liver tumors after 1 year.
      In contrast, low-expressing RE4 mice had normal liver function and histology and
      did not develop liver tumors when examined at 3 to 17 months of age. Moreover,
      hyperediting of apoB and NAT1 mRNA in the liver was robust in the I-20 mice but
      barely detectable in the RE4 mice. The low-level expression resulted in
      sufficient APOBEC-1 to edit essentially all apoB mRNA at the normal editing site,
      virtually eliminating apoB-100 and LDL in the plasma of RE4 mice. When RE4 mice
      were crossed with human apoB transgenic mice, which possess high plasma LDL
      concentrations, plasma LDL levels in the offspring were reduced to very low
      levels. These results indicates that long-term hepatic expression of APOBEC-1 at
      low levels sufficient to eliminate LDL does not cause apparent liver damage or
      liver tumors in transgenic mice. RE4 APOBEC-1 transgenic mice should prove
      valuable for studying the roles of apoB-containing lipoproteins in lipid
      metabolism and atherosclerosis.

PMID- 9633946
TI  - Applications of the FIB lift-out technique for TEM specimen preparation.
AB  - A site-specific technique for cross-section transmission electron microscopy
      specimen preparation of difficult materials is presented. A focused ion beam was
      used to slice an electron transparent membrane from a specific area of interest
      within a bulk sample. Micromanipulation lift-out procedures were then used to
      transport the electron-transparent specimen to a carbon-coated copper grid for
      subsequent TEM analysis. The FIB (focused ion beam) lift-out technique is a fast
      method for the preparation of site-specific TEM specimens. The versatility of
      this technique is demonstrated by presenting cross-sectioned TEM specimens from
      several types of materials systems, including a multi-layered integrated circuit
      on a Si substrate, a galvanized steel, a polycrystalline SiC ceramic fiber, and a
      ZnSe optical ceramic. These specimens have both complex surface geometry and
      interfaces with complex chemistry. FIB milling was performed sequentially through
      different layers of cross-sectioned materials so that preferential sputtering was
      not a factor in preparing TEM specimens. The FIB lift-out method for TEM analysis
      is a useful technique for the study of complex materials systems for TEM
      analysis.

PMID- 9633947
TI  - Superior preservation of the staphylococcal glycocalyx with aldehyde-ruthenium
      red and select lysine salts using extended fixation times.
AB  - The utility of lysine-based aldehyde-ruthenium red fixatives for the preservation
      and/or staining of the fibrous staphylococcal glycocalyx was improved by
      substitution of alternative forms of lysine for the free amino form.
      Paraformaldehyde-glutaraldehyde fixatives containing alternative lysines, with or
      without ruthenium red, were compared at short 20-minute prefixation times and at
      extended overnight fixation times. Although inclusion of paraformaldehyde made
      longer fixation times possible, the length of time for "safe" fixation varied per
      sample and could not be predicted. All alternative lysine forms permitted
      fixation of at least 24 hours without sample loss. The L-lysine monohydrochloride
      or L-lysine acetate forms permitted longer fixation times than the L-lysine free
      amino form, and they had comparable or better preservation of the staphylococcal
      glycocalyx. Thus, the usefulness of aldehyde-lysine-based fixatives with minor
      changes has been enhanced.

PMID- 9633948
TI  - Lack of topography in the ventral nucleus of the lateral lemniscus.
AB  - In contrast to the ease of finding tonotopicity in other nuclei, both anatomical
      and electrophysiological methods have failed to demonstrate a clear and simple
      tonotopic map within the ventral nucleus of the lateral lemniscus (VLL). The
      present study was undertaken in cat with the hope that methods not used
      previously in studies of VLL might succeed in demonstrating an orderliness in its
      exiting fibers (i.e., efferents) or its incoming fibers (i.e., afferents). Since
      the same organization of ascending frequencies present in the cochlea is
      maintained in these fibers as well as in all main auditory nuclei, demonstration
      of a similar organization of frequencies in VLL would be evidence of the cochleo-
      or tono-topicity of this nucleus. Using triple injection of 3 different
      fluorescent dyes in inferior colliculus to study efferents, orderly and tonotopic
      cell-labeling is found in each of the brainstem auditory nuclei, with the notable
      exception of VLL. Instead, labeling of cell clusters, each cluster containing a
      small number of cells, is found randomly distributed throughout VLL in all 3 of
      its spatial dimensions. Using the 2-deoxyglucose (2-DG) method, during
      stimulation at 6 different frequencies, afferent orderliness, indeed,
      tonotopicity is found in all major brainstem auditory nuclei, again with the
      notable exception of VLL. Rather, each frequency evokes 2-DG label throughout
      VLL. In agreement with the results based on electrophysiological methods,
      therefore, the anatomical methods used here also yield no evidence of
      tonotopicity in VLL. Thus, if there is orderliness in VLL's efferents or
      afferents, it is based on an auditory dimension incommensurate with frequency.

PMID- 9633949
TI  - Morphological examination of bone synthesis via direct administration of basic
      fibroblast growth factor into rat bone marrow.
AB  - Woven bone induced by direct injection of basic fibroblast growth factor (bFGF)
      into rat bone marrow was examined. On the first day after injection, fibrous
      tissues formed in the treated region of the bone marrow. Tissue-nonspecific
      alkaline phosphatase (TNAPase)-immunopositive osteoblastic cells and osteopontin
      immunopositive-extracellular matrices were observed in the fibrous tissues,
      indicating bone induction. On the fifth day, the bFGF-induced bone was found
      broadly in the bone marrow. In the originally existing bone, osteopontin
      immunoreactivity was observed at cement lines, but not in the fully calcified
      matrix, whereas the woven bone displayed immunoreactivity throughout the matrix.
      Numerous TRAPase-positive osteoclasts were present on the surfaces of the woven
      bone, but no obvious cement line was observed. Therefore, both bone formation and
      resorption appeared highly active, without normal cellular coupling equilibrated
      between bone formation and resorption performed by osteoblasts and osteoclasts.
      On the tenth day, the bFGF-induced bone was almost replaced by bone marrow. Thus,
      bone formation actively occurred in the first half of the experimental period,
      whereas bone resorption came to be predominant thereafter. This study
      demonstrated that bFGF stimulates bone formation, which, however, is subject to
      subsequent resorption, probably due in part to the absence of coordinated
      cellular coupling between osteoclasts and osteoblasts.

PMID- 9633950
TI  - Photochemically induced focal cochlear lesions in the guinea pig: I. DAB staining
      and SEM study.
AB  - A photochemical reaction was used to produce focal microcirculation disorders in
      the guinea pig cochlea. Temporal bones were removed at various intervals between
      5 minutes and 1 month after infusion of rose bengal (RB) and illumination.
      Infused but unilluminated contralateral cochleae served as controls. Dissected
      cochlear structures were stained by 3,3'-diaminobenzidine (DAB) peroxidase
      substrate medium. After observation by light microscopy (LM), the same specimens
      were processed and observed by scanning electron microscopy (SEM). Dilation of
      strial capillaries and destruction of strial epithelial cells became apparent at
      1 hour after illumination. Tightly packed red blood cells were found filling the
      severed end of markedly dilated strial capillaries at 24 hours after the
      procedure. DAB staining of the osseous spiral lamina indicated vascular change
      with vessel dilation in the illuminated area. At 1 week after illumination, the
      lesion area of the stria vascularis and spiral prominence was replaced by a layer
      of larger, flat cells. At 1 month after illumination, all vascular supply to the
      cochlear lateral wall disappeared at the site of illumination. All lesions
      remained focal and showed no sign of expansion or reduction throughout the
      observation period. The cochlear duct of the guinea pig appears to be segmentally
      nourished by the capillary system. Observation of DAB stained tissue by LM and
      SEM proved to be informative in the study of microcirculation disorders of the
      inner ear.

PMID- 9633951
TI  - Photochemically induced focal cochlear lesions in the guinea pig: II. A
      transmission electron microscope study.
AB  - Photochemically induced focal lesions in guinea pig cochleas were studied by
      light microscopy and transmission electron microscopy. The lesions were induced
      in the second cochlear turns of 35 adult guinea pigs by illumination for 10
      minutes with a focused green light immediately after a rose bengal solution was
      injected into the jugular vein. The cochlear lateral wall and organ of Corti were
      examined 5, 10, 20, 30, and 90 minutes, 12 and 24 hours, and 3, 7, and 30 days
      after the procedure. Aggregations of platelets and red blood cells were found in
      strial capillaries at 5 minutes after illumination. After 30 minutes, marginal
      cell surfaces protruded into the endolymphatic space; surface membranes were
      ruptured and the cytoplasm was expelled into the space. In outer hair cells,
      disruption of the cellular membrane was found near the cuticular plate 12 hours
      after the procedure. All cellular elements of the lateral wall and organ of Corti
      were markedly degenerated in the 30-day specimens. Histological changes found in
      the stria vascularis were consistent with cell damage caused by active oxygen
      species. It is likely that the stria vascularis is more sensitive to the
      photochemical reaction than other parts of the cochlea. Cell damage in other
      parts of the cochlea seemed to have been caused by local microvascular ischemia
      in addition to the action of active oxygen species induced by the photochemical
      reaction.

PMID- 9633952
TI  - Biplane color flow duplex intravenous intravascular ultrasound for arterial
      visualization.
AB  - PURPOSE: To describe a feasibility study in a sheep model using an intravascular
      ultrasound (IVUS) instrument in an intravenous position to produce color flow, B
      mode images of arterial segments along with Doppler blood flow velocities.
      METHODS: Four healthy adult male sheep were anesthetized for surgical exposure of
      the right external jugular vein. A 9.0F sheath was also introduced in the common
      femoral artery for arteriography and device insertion. A 7.5-MHz ultrasound probe
      with 1-cm graduation markers was passed into the jugular vein. B-mode and color
      flow pictures were captured at aortic branches in cross and longitudinal
      sections. Length measurements between aortic branches and Doppler spectral
      velocities were obtained. Guidewire, balloon, and stent maneuvers were monitored
      by the stationary intravenous IVUS probe. RESULTS: High-quality visualization of
      the entire abdominal aorta and its branches was achieved in all animals. With the
      probe stationary in the vena cava, a 1.5-cm linear segment of the aorta could be
      continuously observed in both B-mode and color flow ultrasound scans. Insertion
      and implantation of a Palmaz balloon-expandable stent was guided by intravenous
      IVUS alone. Selective catheterization of the right renal artery was followed
      visually by moving the intravenous IVUS probe sequentially. CONCLUSIONS:
      Intravenous IVUS appears feasible as a guidance and monitoring tool for
      endovascular interventions. While conventional IVUS provides only cross-sectional
      images in B-mode, intravenous IVUS captures color flow and Doppler velocity data
      as well. These added ultrasound modalities may offer potential advantages for
      guidance of endovascular procedures and endoleak detection.

PMID- 9633953
TI  - Intravascular ultrasound in endovascular stent-grafts for peripheral aneurysm: a
      clinical study.
AB  - PURPOSE: To evaluate the potential diagnostic information of intraprocedural
      intravascular ultrasound (IVUS) in patients undergoing endovascular stent
      grafting for peripheral aneurysm. METHODS: IVUS was used in 17 patients
      preprocedurally to measure the diameter of the proximal and distal neck and the
      length of the aneurysm. Balloon and stent-graft sizes were selected based on
      these measurements. Following stent-graft deployment, angiography and IVUS were
      used to document stent apposition and the configuration and diameter of the stent
      graft. RESULTS: Stent-graft insertion was considered successful in 8 patients
      based on angiography and IVUS images. In 9 others, both imaging modalities showed
      inadequate results, necessitating 12 additional procedures: balloon angioplasty
      for stent-graft stenosis (2) and inadequate stent-graft apposition (1); an
      additional stent-graft (4); an extra stent (1); thrombectomy (2); and conversion
      (2) for inadequate stent-graft position and a graft rupture. In these patients,
      intraprocedural IVUS was superiorto angiography in contributing vital information
      to aid in the selection of the additional interventions. CONCLUSIONS: During
      management of peripheral aneurysms with endovascular stent-grafts, IVUS
      monitoring was a useful adjunct when the initial procedure was unsatisfactory
      and/ or when intraprocedural angiographic studies were inconclusive.

PMID- 9633954
TI  - Diameter of large balloons used in endoluminal graft deployment varies with
      inflation pressure.
AB  - PURPOSE: To evaluate the characteristics of large-diameter balloon catheters used
      during endoluminal repair of aortic aneurysms. METHODS: Thirty-three large
      balloon dilatation catheters in the diameter range of 15 to 30 mm were measured
      at controlled pressures from 1 to 4 atm. The balloons were inflated with water
      using an inflation syringe connected to a pressure transducer. Diameters at
      stable pressure and pressure changes against time were recorded for each balloon.
      RESULTS: Dilation catheters in the range of 15 to 20 mm in diameter were
      significantly smaller (p < 0.005) than their nominal diameter at 1 and 2 atm;
      they reached nominal diameter only at the relatively high pressure of 4 atm. Most
      larger diameter balloons (25 and 30 mm) did not attain their nominal diameter
      even with pressures up to 4 atm. All sizes of balloon catheters tested became
      relatively compliant at pressures > 3 atm. CONCLUSIONS: The large balloon
      catheters tested in this study were designed for arterial angioplasty or
      valvuloplasty. They attained a significantly smaller size than their nominal
      diameter at pressures < 3 atm and became compliant at pressures exceeding 3 atm.
      Interventionists should be aware of these characteristics when using balloon
      catheters such as these during endoluminal graft deployment. Large balloons that
      reach predictable diameter at lower pressures should be designed specifically for
      use in endoluminal graft procedures.

PMID- 9633955
TI  - Treatment of traumatic false aneurysm of the thoracic aorta with endoluminal
      grafts.
AB  - PURPOSE: Traumatic false aneurysms of the thoracic aorta presenting at a time
      remote from the original injury are a rare but complex problem. The treatment of
      a traumatic false aneurysm by endovascular techniques may offer many advantages
      over conventional open surgery. METHODS AND RESULTS: Two male patients presented
      with traumatic false aneurysm of the thoracic aorta after being treated
      emergently for visceral injuries from a gunshot wound in one and an automobile
      accident in the other. In both cases, the aneurysm was situated so that only the
      T11 intercostal artery would be sacrificed by endoluminal exclusion. Commercially
      available endoluminal stent-grafts (Talent) were deployed successfully. Recovery
      in both patients was rapid and uneventful with no neurological sequelae. Spiral
      computed tomographic scans at 1 year indicated sustained aneurysm exclusion and
      satisfactory endograft position. CONCLUSIONS: A customized endoluminal stent
      graft can be used with great accuracy to exclude thoracic false aneurysms,
      avoiding the potential complexity and morbidity of an open thoracic approach.

PMID- 9633956
TI  - The effect of angulation on intravascular ultrasound imaging observed in vascular
      phantoms.
AB  - PURPOSE: To quantify the error introduced by noncoaxial intravascular ultrasound
      (IVUS) imaging and to evaluate the use of a balloon-tipped catheter in
      compensating for intraluminal angulation and subsequent dimensional inaccuracy.
      METHODS: The effect of noncoaxial IVUS imaging was investigated in both a
      polyvinyl chloride phantom and an in vitro canine aorta using a calibrated setup
      to measure angulation off axis. Imaging was performed at increasing angulation
      (creating an elliptical image) in both phantoms, with the transducer centered and
      off center. Diameters were compared to the original coaxial diameter, as well as
      calculated diameters based on specific angles off axis. The percentage change
      (error) was also calculated at these angles. The measurements were repeated using
      a balloon-tipped catheter to center the transducer. RESULTS: The measured
      diameters and percentage changes compared closely with their calculated
      counterpart. Up to 25 degrees off axis, the apparent increase in diameter
      measurement was nearly 10%. Angulation from 30 degrees to 70 degrees resulted in
      an increase of 15% to 192%. Use of the centering balloon reduced the amount of
      error by 70% to 85% but was limited to angles < or = 25 degrees due to the design
      of the test apparatus. CONCLUSIONS: The error introduced by noncoaxial IVUS
      imaging can be significant and may be partially corrected by the use of a
      centering balloon. Further studies in the clinical application of a centering
      device are warranted.

PMID- 9633957
TI  - Emergent endoluminal repair of delayed abdominal aortic rupture after blunt
      trauma.
AB  - PURPOSE: To report the emergency repair of a traumatic abdominal aortic rupture
      using endoluminal techniques. METHODS AND RESULTS: A 25-year-old female sustained
      multiple head, chest, and abdominal injuries in a motorcycle accident. Six days
      after emergency treatment (including splenectomy and repair of a superficial
      hepatic rupture and lacerations to the stomach, small bowel, and colon), she
      became hemodynamically unstable. A massive retroperitoneal hematoma had evolved
      from a distal aortic rupture. Owing to a hostile abdomen and possibility of
      bacterial contamination, a self-expanding stent-graft was inserted transfemorally
      to repair the aortic injury. The patient recovered uneventfully and continues in
      good health with a patent endograft repair 2 years after treatment. CONCLUSIONS:
      This experience would support the efficacy of endograft implantation for emergent
      repair of trauma aortic injuries; however, proper facilities, an experienced
      interventional team, and an assortment of endografts and stents must be
      available.

PMID- 9633958
TI  - Transluminal stent-graft repair for pseudoaneurysm of PTFE hemodialysis grafts.
AB  - PURPOSE: To report the use of endovascular techniques to treat two cases of
      nonanastomotic pseudoaneurysm of a bridge graft fistula (BGF). METHODS AND
      RESULTS: Two men with fully functional polytetrafluoroethylene (PTFE) BGFs both
      presented with an enlarging mass adjacent to their arteriovenous shunt. The false
      aneurysm in both instances was located by ultrasound and confirmed by shunt
      angiography at the time of surgery. Both fistulas were repaired by transluminally
      introducing a stented graft composed of a balloon-expandable Palmaz stent covered
      with a PTFE graft. Completion arteriography confirmed normal flow through the
      graft with no communication between the lumen and the aneurysmal cavity. Both
      patients recovered without complications and were discharged on the day of the
      procedure. Follow-up data reveal that both fistulas remain fully functional up to
      5 and 6 months, respectively. CONCLUSIONS: Endovascular repair using stent-grafts
      can be a safe and effective method of excluding pseudoaneurysms associated with
      PTFE BGFs.

PMID- 9633959
TI  - Iliofemoral venous thrombosis caused by compression of an internal iliac artery
      aneurysm: a minimally invasive treatment.
AB  - PURPOSE: To report the success of a minimally invasive treatment for phlegmasia
      cerulea dolens without gangrene caused by compression from an internal iliac
      artery aneurysm. METHODS AND RESULTS: An 81-year-old male with a 1-month history
      of paralysis owing to a hemorrhagic stroke presented with massive edema and skin
      mottling of the right lower extremity. Imaging confirmed right iliofemoral deep
      vein thrombosis caused by compression from a 4-cm internal iliac artery aneurysm.
      With thrombolysis ruled out, a minimally invasive treatment plan was undertaken,
      featuring percutaneous coil embolization of the aneurysm and surgical venous
      thrombectomy with proximal arteriovenous fistula creation and iliac vein stent
      placement. Failure of the coils to embolize the iliac aneurysm prompted the use
      of an endovascular graft to exclude the aneurysm. The patient's symptoms
      subsided, and he has a patent right iliofemoral venous system and internal iliac
      artery at his latest (16-month) follow-up. CONCLUSIONS: This case demonstrates
      that minimally invasive endovascular and open techniques can be combined to
      achieve an optimum outcome in patients at high risk for standard surgical
      approaches.

PMID- 9633960
TI  - The vascular laboratory: a critical component required for successful management
      of peripheral arterial occlusive disease.

PMID- 9633961
TI  - Type I and Type II endoleaks: a more useful classification for reporting results
      of endoluminal AAA repair.

PMID- 9633962
TI  - Combined endovascular/laparoscopic approach to aortic pseudoaneurysm repair.

PMID- 9633963
TI  - Understanding tracheomalacia.
AB  - Tracheomalacia is an abnormality of the trachea that probably is present to some
      degree in all infants and children with oesophageal atresia. It causes the
      trachea to collapse during breathing, leading to obstruction of the upper airway.
      Our knowledge of the structural abnormalities underlying tracheomalacia is
      limited, mainly because patients with oesophageal atresia usually survive.
      Recently, the Adriamycin-induced rat model of oesophageal atresia and
      tracheomalacia has clarified some aspects of its pathology and the factors which
      may influence its development. The rat model suggests that the same detrimental
      factors that cause oesophageal atresia might also affect the development of the
      trachea, and that anomalous great vessels may exacerbate the severity of
      tracheomalacia locally.

PMID- 9633964
TI  - Medical student education in paediatrics and child health: where are we going?
AB  - In most undergraduate medical curricula, learning is becoming less content based
      and the emphasis is changing to problem based learning, continuing self directed
      learning, and the use of a wide range of learning resources. Particular needs in
      paediatrics and child health are an increasing emphasis on learning in ambulatory
      care and community based health facilities, and on assessment processes which are
      formative and reflect the learning objectives appropriately. A wide range of
      resources is needed for learning at a time when teaching hospital and health
      system facilities face significant financial restraints.

PMID- 9633965
TI  - Reducing the risk of sudden infant death syndrome: a review of the scientific
      literature.
AB  - In March 1997 a multidisciplinary forum was convened by the National SIDS Council
      of Australia to review recent evidence concerning risk factors of sudden infant
      death syndrome (SIDS) and to revise and refine the current guidelines for
      reducing the risk of SIDS. The forum provided an assessment of the evidence for
      recommendations to reduce the risk of SIDS using an evidence-based process.
      Strong evidence has now accumulated that the intervention campaigns to reduce
      prone sleeping during infancy have been followed by SIDS rate declines. Recent
      data indicate that the supine position is not associated with an increase in
      significant morbidity outcomes and provides greater protection for SIDS than the
      side position, which may be unstable. Covering of the baby's head by bedding is
      strongly related to SIDS. The infant's sleeping environment should be carefully
      set up to ensure that the baby's head, including the face, cannot be obstructed
      during sleep. Parental smoking is strongly associated with SIDS. Structural
      supportive interventions for parental smoking cessation are required. Bedsharing
      increases the risk of SIDS amongst smokers and the data are currently not
      sufficient to provide complete reassurance to nonsmoking parents that bedsharing
      is safe. Infants should be maintained in a comfortable temperature zone. The
      evidence for a protective effect of breast-feeding is conflicting, so breast
      feeding cannot be promoted strongly as reducing the risk of SIDS. Immunisation
      has not been associated with SIDS. Parents and carers should be aware of the
      current guidelines. Health professionals should also be aware of the evidence on
      which the current recommendations are based. Effective health education
      programmes should lead to a further decline in SIDS mortality in Australia.

PMID- 9633966
TI  - Education for children with disabilities: the rationale for inclusion.
AB  - OBJECTIVE: To discuss issues in the education of children with disabilities,
      particularly with respect to inclusion in mainstream classes. METHODOLOGY: Review
      of the literature on education for children with disabilities, focusing on the
      inclusion versus segregation debate. RESULTS: The literature provides no support
      for segregation and some support for the view that segregated children are
      disadvantaged. What seems to be important is the way the child is educated rather
      than where the education takes place. In addition, there are ethical,
      sociological, and legal arguments in favour of an inclusive educational system.
      CONCLUSIONS: There are good arguments to encourage inclusive education for
      children with disabilities. In advising parents, doctors should focus on how
      rather than where the child with a disability should be educated.

PMID- 9633967
TI  - Urinary calcium excretion in Chinese adolescents.
AB  - OBJECTIVES: To obtain normative reference values for urinary calcium excretion in
      Chinese adolescents. METHODOLOGY: A random group of 425 healthy Chinese
      adolescents aged 12-19 years were recruited from secondary schools in Hong Kong.
      Each subject provided a sample of morning urine for the assessment of calcium and
      creatinine excretion. A subgroup of 80 subjects provided a 24-h urine sample for
      assessment of daily calcium excretion. RESULTS: The mean (+/-S.D.) and median
      urinary calcium/creatinine concentration ratios (UCa/Cr) expressed in mmolmmol
      creatinine were 0.18 (+/-0.16) and 0.12. Girls had a higher UCa/Cr than boys (P <
      0.0001). The mean+/-S.D. 24-h urinary calcium excretion was 0.043+/-0.025 mmol kg
      day(-1) (1.71+/-1.01 mg kg day(-1)). CONCLUSION: The UCa/Cr ratio and 24-h
      urinary calcium excretion are low when compared with published values for
      Caucasian children. The apparent rarity of nephrolithiasis and microscopic
      haematuria associated with hypercalciuria may be related to the low urinary
      calcium excretion in this population.

PMID- 9633968
TI  - Humoral immune and clinical responses to food antigens following acute diarrhoea
      in children.
AB  - OBJECTIVE: To investigate the effect of acute watery diarrhoea in children upon
      humoral immune responses to food antigens and the subsequent development of food
      allergy. METHODOLOGY: Serum antibodies to cows' milk, beta-lactoglobulin, alpha
      lactalbumin, bovine serum albumin and ovalbumin were measured in 30 children with
      acute diarrhoea in the acute phase and 1 month after recovery. The children were
      followed for 1 year to assess the development of food allergy. RESULTS: IgG
      antibeta-lactoglobulin titres for the study group increased 1 month after
      recovery compared to the titres during the acute phase (P = 0.02). Antibody
      concentration for the other antigens studied did not rise. Four children
      developed positive IgE antibodies to one or more of the allergens after the
      diarrhoeal episode, although the titres were very low. None showed evidence of
      allergy to cows' milk or egg during the year-long follow-up. CONCLUSIONS: Acute
      diarrhoea in children resulted in increased production of IgG antibody to beta
      lactoglobulin and had a priming effect for development of positive IgE antibody
      to cows' milk. Clinical food allergy was not observed in any of the children
      during the year-long follow-up.

PMID- 9633969
TI  - Congenital malformations in Victoria, Australia, 1983-95: an overview of infant
      characteristics.
AB  - OBJECTIVE: To provide an overview of the characteristics of Victorian infants
      born between 1983 and 1995 who are affected by one or more of 27 sentinel birth
      defects. METHODOLOGY: Using data on congenital malformations supplied to the
      Victorian Perinatal Data Collection Unit from multiple sources between 1983 and
      1995, information was summarised for 25231 infants (born at 20 weeks or more) and
      1566 terminations of pregnancy before 20 weeks' gestation. RESULTS: During the 13
      year study period in Victoria, 3.2% of babies had at least one malformation.
      Congenital dislocation of the hip was the most common defect with a prevalence of
      28.9 per 10000 pregnancies or 1/346. Increase in birth prevalence between 1983
      and 1995 is greatest in obstructive defects of the renal pelvis, hypospadias and
      the trisomies 21,13 and 18. Nearly 50% of pregnancies affected by anencephaly
      were terminated before 20 weeks compared to 26% affected by spina bifida. The
      perinatal mortality of infants born at 20 weeks or more with congenital
      malformations is more than 10 times greater than that of infants without any
      malformations. Males are more at risk of being born with a malformation than
      females. Congenital malformations are more common in infants of multiple
      pregnancies and those of low birthweight. CONCLUSION: This large data collection
      is a valuable source of information for perinatal epidemiologists, for providers
      of prenatal diagnostic services and for the care of the disabled. In addition,
      the continued reporting and monitoring of birth defects will allow for targeted
      research that may lead to a better understanding of their aetiology.

PMID- 9633970
TI  - Is a paediatrician needed at all Caesarean sections?
AB  - OBJECTIVE: The need for a skilled neonatal resuscitator in the form of a
      paediatrician or paediatric registrar to attend a vaginal delivery or Caesarean
      section (CS) is not clearly defined. This study was undertaken in order to
      ascertain the level of resuscitation a neonate might require dependent on the
      delivery mode and type of anaesthesia used. METHODOLOGY: We analysed the
      Tasmanian Obstetric Audit from 1980 to 1989 for the need for intubation and Apgar
      scores at 1 min of term singleton deliveries by the mode of delivery. RESULTS:
      The number of singleton term deliveries was 64739. When the data were analysed
      annually there was a trend for a reduction in the need for intubation in CS
      deliveries during the first 5 years, although this was not paralleled by an
      improvement in Apgar scores. Thus the intubation rate data are also presented for
      the last 5 years of the study. The intubation rate, Apgar score at 1 min of < 4,
      and Apgar score at 1 min of > or = 4 < 7 for repeat CS under epidural anaesthesia
      were 0.55% (0.26% for 1985-89) 0.83% and 3.58%, respectively, with relative risks
      when compared with spontaneous normal vaginal delivery of 1.8 (1.2 for 1985-89),
      0.7 and 0.5, respectively. The relative risk of these outcomes was higher than
      for normal vaginal delivery for all other modes of delivery including repeat CS
      under general anaesthesia. CONCLUSION: It is concluded that a paediatrician or
      paediatric registrar is not required to routinely attend repeat CS under epidural
      anaesthesia, but should be present for repeat CS under general anaesthesia.

PMID- 9633971
TI  - Developmental-behavioural problems in general paediatrics.
AB  - OBJECTIVE: To determine the current role of private general paediatrics in the
      care of children with problems of development and behaviour. METHODS: We surveyed
      all general paediatricians registered with the Australian College of Paediatrics
      to assess their current role in developmental-behavioural (DB) problems--their
      rate of referrals, their role in the continuing management, and opinions
      regarding duration of training in this area. RESULTS: Of 394 questionnaires sent,
      284 replies were received (72%). From these 284 we analysed results for all 172
      who spent more than 25% of their time in private general paediatric practice. On
      average, 32% of new referrals were for DB problems. With 10 DB clinical vignettes
      presented, paediatricians chose to continue to manage in conjunction with allied
      health services in 65% of cases. Other management choices included referral to a
      multidisciplinary team (16%), referral elsewhere (10%) and manage alone (7%). For
      training to be a general paediatrician, they indicated 3 months should be spent
      during basic training in each of the three areas of; DB paediatrics,
      developmental disabilities and child psychiatry (separately or concurrently); and
      6 months of each during advanced training. Free comments highlighted lack of
      public allied health and psychosocial services. CONCLUSION: Private community
      based general paediatricians are deeply involved in this area of work. The
      results raise questions about services for training and for clinical
      collaboration between public and private child health providers.

PMID- 9633972
TI  - Iron status and dietary iron intake of 6-24-month-old children in Adelaide.
AB  - OBJECTIVE: Chronic iron deficiency in children is associated with anaemia and
      impaired mental and psychomotor development. The aim of this study was to assess
      the iron status and dietary intake of 6-24-month-old Caucasian and Asian children
      living in metropolitan Adelaide. METHOD: A total of 234 healthy children (82%
      Caucasian and 18% Asian) aged 6-24 months were studied. Dietary iron intake of
      children was estimated from semiquantitative diet recall questionnaire
      administered to their parents. Blood samples for full blood count, serum ferritin
      (SF), serum iron (SI) and transferrin (TF) level estimations were obtained by
      venesection. Based on the laboratory test results, infants were classified as
      iron sufficient (IS) if the haemoglobin (Hb) concentration was > 110 g L(-1), SF
      > or = 15 microg L(-1), TF2 3.0 g L(-1), SI > or = 8 micromol L(-1) and iron
      saturation (ISAT) > or = 12%; or nonanaemic iron deficiency (NAID) if the Hb
      concentration was > 110 g L(-1) and SF < 15 microg L(-1) or SI < 8 micromol L(
      1), TF > 3.0 g L(-1), and ISAT < 12%; or as iron deficiency anaemia (IDA) if the
      Hb concentration was < 110 g L(-1) in association with SF < 15 microg L(-1) or
      with SI < 8 micromol L(-1), TF > 3.0 g L(-1) and ISAT < 12%. RESULTS: Sixty-nine
      per cent of Caucasian children were classified IS, 25% as NAID and 6% were IDA;
      while 72% of Asian children were classified IS, 14% as NAID and 14% were IDA.
      Multivariate analysis demonstrated that factors associated with iron deficiency
      (SF </5 microg L(-1)) included age, duration of breast-feeding and cows' milk
      intake. CONCLUSION: Iron deficiency is common in our young population. Additional
      strategies to prevent IDA need be developed and evaluated in Australian infants.

PMID- 9633973
TI  - Children's understanding of sun protection behaviours: a comparative analysis.
AB  - OBJECTIVE: To investigate awareness of sun protection behaviours in a sample of
      primary school children in New Zealand. METHODOLOGY: Information was collected
      from 824 primary school children in New Zealand using a drawing and writing
      technique. RESULTS: The data revealed a bias towards sunscreen as a method of sun
      protection compared with other methods such as clothing and the use of shade.
      Comparisons between results obtained from children resident in Australia and
      England indicated a greater awareness of sun protection methods amongst the
      children from Australia and New Zealand compared with those children living in
      England. CONCLUSIONS: Children as young as 5 and 6 can describe the consequences
      of overexposure to the sun, and can illustrate methods of sun protection.
      Sunscreen is seen as the main method of sun protection.

PMID- 9633974
TI  - Sleep deprivation or postnatal depression in later infancy: separating the
      chicken from the egg.
AB  - OBJECTIVES: To explore the association between maternal distress and depression
      in the first years of a newborn's life and the child's sleeping behaviour and
      problems associated with this behaviour. To asses the effectiveness of an
      outpatient-based individualised behaviour modification programme to modify
      children's sleep behaviour and to decrease levels of maternal distress and
      depression. METHOD: Families were referred to an outpatient childhood sleep
      problems clinic. Intervention consisted of an individualised management programme
      including recognised modes of child sleep behaviour management ('controlled
      crying', 'cold turkey,' rewards) together with occasional use of short-term (less
      than 2 weeks) tapering dose sedating medication for the child. Two months after
      the initial contact with the clinic, families completed a second questionnaire
      collating similar data to that collected at time of enrolment. RESULTS: A total
      of 114 consecutive families referred to the clinic provided initial data. Follow
      up questionnaires were returned by 70 (61%). Significant change was recorded in
      children's sleep parameters including reduction in mean number of night time
      awakenings (4.1-1.3, P < 0.001), proportion of children requiring longer than 30
      min to settle at night (49% to 21%, P < 0.01) and in the proportion of children
      settling after 8 pm (51% to 33%, P < 0.01). Sleep problem rating on a 0-10 scale
      decreased from a mean of 8.1-3.1 (P < 0.001). On initial assessment, 40% of
      mothers had Edinburgh Postnatal Depression Scale (EPNDS) scores greater than 12
      (screening cut-off point). At repeat assessment, 4.3% had scores greater than 12.
      The mean score on the EPNDS fell from 11.2 to 5.8 (P < 0.001). CONCLUSIONS: An
      outpatient-based individualised approach to modifying children's problematic
      sleep behaviour using recognised behaviour management techniques is effective.
      Modification of problematic childhood sleep behaviour is associated with
      significant improvement in maternal mood. Given the high incidence of childhood
      sleep problem and diagnosed postnatal depression, it is likely significant
      numbers of mothers being diagnosed as having postnatal depression are suffering
      the effects of chronic sleep deprivation. Management of postnatal mood disorder
      and childhood sleep behaviour must occur with due recognition to their close
      association.

PMID- 9633975
TI  - Childhood sleep problems: association with prenatal factors and maternal
      distress/depression.
AB  - OBJECTIVE: To determine whether problems with childhood sleep behaviour are
      associated with either maternal sleep patterns and emotional status during the
      pregnancy period, or levels of maternal distress and depression during the
      postnatal period. METHODOLOGY: A case/control comparison study. Cases were
      families presenting for admissions to a mother/baby hospital in Brisbane with the
      major presenting problem being the child's sleep behaviour. The control group
      consisted of families presenting for well child health care to one of four child
      health centres in suburban Brisbane. Each participating mother provided
      information by way of a self-report questionnaire on social and demographic
      variables, children's sleep patterns, maternal emotional adjustment and maternal
      sleep pattern during the pregnancy, and current problem with child's sleep
      behaviour. Current level of maternal distress/depression, was measured using the
      Edinburgh Postnatal Depression Scale. Cases were compared with controls on all
      these variables. RESULTS: Significant differences were found between groups in
      childhood sleep parameters, degree of problem related to childhood sleep,
      maternal sleep variables during the entire pregnancy, and current levels of
      maternal distress/depression. CONCLUSION: The origins of problematic childhood
      sleep behaviour may lie in the pregnancy period. Levels of maternal distress and
      depression are associated with problematic childhood sleep behaviour. The issue
      of whether childhood sleep problem predisposes to maternal distress/depression
      needs exploration. Assessment of maternal mood disorder or childhood sleep
      problems should be comprehensive and involve both the maternal infant dyad and
      the family network.

PMID- 9633976
TI  - Paediatric assessment in a residential child and adolescent psychiatry unit.
AB  - OBJECTIVE: To document the health status, comorbidity and functional impairments
      experienced by a group of psychiatrically disturbed children and adolescents.
      METHODOLOGY: A detailed study of consecutive admissions to a residential unit
      over a two-year period was undertaken. All admissions had a comprehensive
      paediatric, speech pathology and psychiatric assessment. RESULTS: Compared to the
      general population, there was a significant history of developmental delay and
      low birthweight, but only a slightly greater prevalence of antenatal problems.
      Clumsiness (37%), severe speech and language disorder (32%), and hearing loss
      (15%) were prominent. Only 25% had no history of comorbid medical or neurological
      disorders. CONCLUSION: Children and adolescents presenting with moderate to
      severe mental health morbidity may have pre-existing comorbid medical problems,
      as well as unrecognised difficulties and impairments in other skills areas.
      Multidisciplinary assessment and intervention should be an integral part of the
      residential programme.

PMID- 9633977
TI  - Carrier identification in X-linked immunodeficiency diseases.
AB  - OBJECTIVE: Carrier identification in X-linked immunodeficiency disorders can be
      based on the demonstration of non-random X inactivation (NRXI) in affected blood
      cell lineages when growth is impaired in cells expressing the abnormal gene. We
      examined the utility of seeking evidence of NRXI to test the carrier status of
      women in families affected by X-linked severe combined immunodeficiency (XSCID)
      and X-linked hypogammaglobulinaemia (XLH), to identify as carriers the mothers of
      boys with SCID or hypogammaglobulinaemia whose phenotype suggested X-linkage and
      to infer X-linkage in boys with SCID or hypogammaglobulinaemia whose disease was
      not clearly X-linked on the basis either of family history or clinical and
      immunological characteristics. METHODOLOGY: A polymerase chain reaction-based
      method was used to amplify a polymorphic CAG repeat in the first exon of the
      androgen receptor gene after selective digestion of the active X chromosome with
      a methylation-sensitive enzyme, HpaII to distinguish between the paternal and
      maternal alleles and to identify their methylation status. RESULTS:
      Heterozygosity was found in 24 of 31 female subjects (77%). As anticipated, NRXI
      could be demonstrated in all lymphoid cells studied from obligate carriers of
      XSCID and an obligate carrier of XLH but not on a carrier of X-linked
      immunodeficiency with hyper-IgM. The finding of NRXI in the mother of a boy with
      a SCID variant showed her to be a carrier of XSCID and establishes that her son
      has XSCID, not otherwise evident from available data. CONCLUSIONS: This PCR assay
      provides a rapid method for carrier detection of X-linked immunodeficiencies, and
      has allowed us to expand the phenotype of XSCID

PMID- 9633978
TI  - Clonidine poisoning--an emerging problem: epidemiology, clinical features,
      management and preventative strategies.
AB  - OBJECTIVE: To ascertain whether the incidence of clonidine poisoning in children
      has increased given the probable increase in clonidine use for treatment of
      childhood behavioural disorders. METHODS: Cases of clonidine poisoning requiring
      hospital admission between 1985-95 inclusive were reviewed and demographic data
      pertinent to each admission were recorded. A literature review was also
      performed, with particular emphasis on incidence, clinical presentation and
      management of clonidine poisoning. RESULTS: There were 14 cases of clonidine
      poisoning during the specified period eight cases presenting in the last 2 years.
      These eight children or their siblings had been prescribed clonidine for
      behavioural disorders. The most common signs at presentation were alteration of
      conscious state (71%) and bradycardia (50%). Nine children were given activated
      charcoal while seven cases underwent gastric lavage or induced emesis. Although
      six children were admitted to intensive care, length of hospital stay was less
      than 24 h in all cases and all had a favourable outcome. CONCLUSION: We concluded
      that the incidence of clonidine poisoning had increased over the specified period
      and that, based on our results, this was likely to be due to an increase in
      clonidine use in childhood behavioural disorders. Based on our data and that from
      literature review it was evident that there are inconsistencies in the management
      of clonidine poisoning and that safety measures, namely packaging and education,
      are inadequate given the increasing profile of clonidine use.

PMID- 9633979
TI  - Cardiac manifestations in tuberous sclerosis: a 10-year review.
AB  - OBJECTIVE: Tuberous sclerosis is a genetic disorder with multisystem involvement.
      The aim of this study was to focus primarily on the cardiac aspects of this
      condition. METHOD: This review included 10 children with tuberous sclerosis
      presenting to our department during a 10-year period. RESULTS: From our data, 80%
      were found to have cardiac involvement. There was an equal prevalence of
      neurologic complications. CONCLUSIONS: Cardiac tumours and seizures were the most
      common problems encountered. Whereas most patients had no symptoms referable to
      the cardiovascular system and required no active intervention, many of those with
      neurologic involvement needed appropriate treatment.

PMID- 9633980
TI  - Child and parent perceptions of stimulant medication treatment in attention
      deficit hyperactivity disorder.
AB  - OBJECTIVE: To evaluate child and parent perceptions of treatment with stimulant
      medication in a sample of children with attention deficit hyperactivity disorder
      (ADHD). METHODOLOGY: Child and parent perceptions questionnaires were completed
      for 102 subjects participating in a double-blind, crossover trial of
      methylphenidate (MPH) and dexamphetamine (DEX). RESULTS: Most children viewed
      medication effects favourably, although 12.7% and 18.8% of children reported
      feeling worse than usual when taking MPH and DEX, respectively. There was
      disagreement between the child's and parents' perceptions of response in over one
      quarter of cases. Most disagreements involved parents viewing the child's
      response favourably, but the child rating reporting an unfavourable outcome. Side
      effects were the main determinant of children's perceptions of adverse response.
      CONCLUSIONS: A substantial proportion of children with ADHD experience treatment
      with stimulant medication adversely. Side-effects are the principal determinant
      of negative child perceptions. Parental report is usually in agreement with child
      report; however, parental report alone is not infallible in providing reliable
      information regarding effects as experienced by the child.

PMID- 9633981
TI  - Renal tuberculosis in an Australian-born child.
AB  - This report describes a case of renal tuberculosis, complicated by hypertension
      and ureteric obstruction, in a previously well Australian born child. Despite
      antituberculous chemotherapy and ureteric stenting, there was a progressive loss
      of renal function in the right kidney until surgical nephrectomy allowed full
      recovery. A high level of clinical suspicion is necessary for a diagnosis of
      genitourinary tuberculosis. Ureteric cicatrisation and obstruction occasionally
      may occur with healing, and therefore serial renal tract imaging during treatment
      is necessary to detect this complication.

PMID- 9633982
TI  - Massive subdural haematoma: an unusual complication of septicaemia in preterm
      very low birthweight infants.
AB  - Non-traumatic massive subdural haematoma is a rare condition in newborn infants
      and is usually associated with hereditary coagulation disorders or congenital
      vascular malformation. Its occurrence in preterm very low birthweight infants
      secondary to systemic bacterial infection has not been reported. We describe two
      extremely preterm neonates who developed massive subdural haematoma as a result
      of gram-negative septicaemia and disseminated intravascular coagulation. Both
      infants suffered severe parenchymal cerebral injury and hydrocephalus. Clinicians
      should be aware of this unusual and catastrophic complication if a very low
      birthweight infant with severe sepsis and disseminated intravascular coagulation
      suddenly deteriorates despite successful treatment with antibiotics. Radiological
      imaging by cranial ultrasound or computed tomography scanning should be routinely
      considered in all such infants for the detection of intracranial bleeding.

PMID- 9633983
TI  - Transient erythroblastopenia of childhood associated with transient neurologic
      deficit: report of a case and review of the literature.
AB  - OBJECTIVE: Patients with transient erythroblastopenia of childhood (TEC) may also
      have a transient neurologic disorder. We present a case history and propose a
      mechanism for this syndrome. PATIENT AND METHODOLOGY: We describe a 20-month-old
      girl with TEC and transient hemiparesis. Records from the period January 1993
      through December 1994 were reviewed to identify other patients with TEC and to
      determine whether neurologic deficits were noted in these cases. RESULTS: Of
      seven patients diagnosed with TEC over a 2-year period, only one had a neurologic
      deficit. This child's hemiparesis resolved within 24 h after the appearance of
      her symptoms. Her TEC resolved within 4 weeks, without long-term sequelae. Our
      experience and review of the literature suggest that focal neurologic deficits in
      TEC patients are uncommon, transient, lack long-term sequelae, and usually
      resolve prior to hematologic recovery. CONCLUSIONS: Previous reports suggested
      that the anaemia resulting from TEC might induce neurologic deficits. We suggest
      an alternative mechanism in which viral infection triggers a host immune response
      that independently leads to both TEC and neurologic abnormalities. Future studies
      should address the role of viral infection in TEC patients with focal
      neuropathies.

PMID- 9633984
TI  - Glutaric aciduria type 1: an underdiagnosed cause of encephalopathy and dystonia
      dyskinesia syndrome in children.
AB  - Two cases of glutaric aciduria type 1 (GA 1) are presented. GA 1 is probably
      underdiagnosed and misdiagnosed, and may explain a proportion of cases of
      extrapyramidal and 'postencephalitic' cerebral palsy. Most cases of GA 1 present
      with a severe dystonic-dyskinetic syndrome following an acute encephalopathy.
      Asymptomatic cases have also been described, complicating genetic counselling and
      prenatal diagnosis. We raise awareness of GA 1 and stress that if clinically
      suspected, immediate institution of therapy may reduce late morbidity. Moreover,
      if recognised in the presymptomatic stage, early institution of treatment may
      prevent the onset of neurological symptoms. GA 1 is an inborn error of lysine and
      tryptophan catabolism, caused by deficiency of the enzyme, glutaryl coenzyme-A
      dehydrogenase. Urine organic acid analyses may be negative. Blood acylcarnitine
      profile has recently been employed as a more sensitive test but was negative in
      both our patients. Enzyme assay remains the definitive diagnostic test.

PMID- 9633985
TI  - Mycoplasma encephalitis--should we be thinking more about it?

PMID- 9633986
TI  - Thyroglossal duct cyst or ectopic thyroid gland?

PMID- 9633987
TI  - Emergency management skills of south Australian paediatric trainees.

PMID- 9633988
TI  - Lest we forget acute epiglottitis.

PMID- 9633989
TI  - Mechanism of action of diazaborines.
AB  - The diazaborine family of compounds have antibacterial properties against a range
      of gram-negative bacteria. Initially, this was thought to be due to the
      prevention of lipopolysaccharide synthesis. More recently, the molecular target
      of diazaborines has been identified as the NAD(P)H-dependent enoyl acyl carrier
      protein reductase (ENR), which catalyses the last reductive step of fatty acid
      synthase. ENR from Mycobacterium tuberculosis is the target for the front-line
      antituberculosis drug isoniazid. The emergence of isoniazid resistance strains of
      M. tuberculosis, a chronic infectious disease that already kills more people than
      any other infection, is currently causing great concern over the prospects for
      its future treatment, and it has reawakened interest in the mechanism of
      diazaborine action. Diazaborines only inhibit ENR in the presence of the
      nucleotide cofactor, and this has been explained through the analysis of the x
      ray crystallographic structures of a number of Escherichia coli ENR-NAD+
      diazaborine complexes that showed the formation of a covalent bond between the
      boron atom in the diazaborines and the 2'-hydroxyl of the nicotinamide ribose
      moiety that generates a noncovalently bound bisubstrate analogue. The
      similarities in catalytic chemistry and in the conformation of the nucleotide
      cofactor across the wider family of NAD(P)-dependent oxidoreductases suggest that
      there are generic opportunities to mimic the interactions seen here in the
      rational design of bisubstrate analogue inhibitors for other NAD(P)H-dependent
      oxidoreductases.

PMID- 9633990
TI  - Selective depletion of DNA precursors: an evolving strategy for potentiation of
      dideoxynucleoside activity against human immunodeficiency virus.
AB  - Human immunodeficiency virus type 1 (HIV-1) is wholly dependent on its host cell
      for a variety of essential metabolites. Among the latter are the deoxynucleoside
      5'-triphosphates (dNTPs) required for reverse transcription of the single
      stranded RNA viral genome into double-stranded viral DNA. Since viral DNA
      synthesis has an absolute requirement for all four dNTPs, restriction of a single
      one of these is sufficient to inhibit HIV-1 replication. To date, this
      therapeutic strategy has been most successful when depletion of the individual
      dNTP is coupled with exposure to its corresponding chain-terminating
      dideoxynucleoside (ddN). While several examples of such combined therapy have
      been defined and studied in vitro, that which has been investigated most
      extensively at both the laboratory and the clinical level is ddATP exposure
      combined with dATP depletion [with dATP restriction being induced by the
      ribonucleotide reductase inhibitor hydroxyurea (HU) and ddATP generated from its
      prodrug 2',3'-dideoxyinosine (ddI)]. Several long-term clinical trials of the
      hydroxyurea/2',3'-dideoxyinosine combination have been completed, with plasma
      viral RNA being reduced to undetectable levels in a substantial fraction (one
      third to one-half) of the patients treated. The major advantages of this and
      analogous combinations discussed in this review are their low cost relative to
      other current multiple drug protocols and their potential for retention of
      activity against drug-resistant HIV mutants.

PMID- 9633991
TI  - Alcohol-mediated increases in acetaminophen hepatotoxicity: role of CYP2E and
      CYP3A.
AB  - This commentary focuses on the roles of CYP3A and CYP2E in alcohol-mediated
      increases in acetaminophen hepatotoxicity. CYP2E has been considered to be the
      main form of P450 responsible for such toxicity in animals and humans. However,
      CYP3A, which is also induced by alcohol, has been shown to have a greater
      affinity for acetaminophen than CYP2E. Previous experiments implicating CYP2E in
      alcohol-mediated increases in acetaminophen hepatotoxicity have used inhibitors
      of this form of P450 that are now proving to be non-specific.
      Triacetyloleandomycin (TAO) is a potent inhibitor of CYP3A that maintains
      specificity in vitro over a large concentration range. In rats treated with
      ethanol or the combination of ethanol and isopentanol, the major higher chain
      alcohol in alcoholic beverages, TAO protects animals from increases in
      acetaminophen hepatotoxicity, suggesting a major role of CYP3A. CYP2E may not
      have a major role due to the rapid loss of induced levels in the absence of
      continued exposure to ethanol. Knockout mice, which are being used to define the
      role of particular proteins in biological responses, have been developed for
      CYP2E1 and CYP1A2 but not CYP3A. Cyp2e1(-/-) and Cyp1a2(-/-) mice are more
      resistant to acetaminophen hepatotoxicity than wild-type strains, even though the
      amounts of the other forms of P450s are unaltered in the liver. These findings
      suggest that the relative amounts of P450s and not just kinetic characteristics
      determine their role in acetaminophen hepatotoxicity. The clinical implications
      of the findings that CYP3A can have a major role in acetaminophen-mediated
      hepatotoxicity are discussed.

PMID- 9633992
TI  - Role of additional mutations outside the YMDD motif of hepatitis B virus
      polymerase in L(-)SddC (3TC) resistance.
AB  - L(-)SddC (3TC) has been shown to be the most promising nucleoside analogue used
      for the treatment of hepatitis B virus (HBV) infection. Unfortunately, it has
      been reported that about 12% of HBV-infected patients experience a recurrence of
      HBV after a period of treatment with 3TC. Point mutations were detected in the
      HBV polymerase of those viruses from 3TC-resistant patients. A common mutation
      occurred at methionine in the YMDD motif. In this report, we present mutants that
      were generated from the HBV genome (adr subtype) by site-directed mutagenesis
      based on clinical reports from other investigators. With the transient
      transfection system, it was found that by changing methionine to valine or
      isoleucine at the YMDD motif, the viral DNA replication would be more than 100
      fold less efficient than that of the wild-type virus. Some additional mutations
      outside the YMDD motif could enhance the replication of the virus containing a
      YMDD mutation. Various levels of resistance to 3TC were observed in HBV mutants
      containing point mutations both inside and outside the YMDD motif. These results
      suggest that the mutations outside the YMDD motif compensate the YMDD mutation to
      some extent for the viral replication and may also contribute to clinical viral
      resistance to 3TC.

PMID- 9633993
TI  - Elevation of endogenous nucleophiles in rat lung by cysteine and glutathione
      esters in vitro.
AB  - In this study, we have compared the uptake of L-cysteine (L-CySH), D-cysteine (D
      CySH), L-cysteine isopropyl ester (L-CIPE) and D-cysteine isopropyl ester (D
      CIPE) in rat lung slices and tracheal sections and determined the effectiveness
      of glutathione (GSH), GSH isopropyl monoester, GSH isopropyl diester, gamma
      glutamylcysteine (gamma-glu-cys) isopropyl monoester and gamma-glu-cys isopropyl
      diester to elevate and prolong intracellular GSH concentrations in rat lung
      slices. Lung slices were incubated with 1.0 mM of thiol and the concentrations
      determined intracellularly and extracellularly with time. Slices incubated with
      GSH, GSH isopropyl diester and gamma-glu-cys isopropyl diester had cellular GSH
      concentrations increased by up to 60%, 95% and 58%, respectively, whereas GSH
      isopropyl monoester and gamma-glu-cys isopropyl monoester did not increase the
      intracellular GSH concentration. Extracellularly, the GSH concentration had
      decreased by 15%, GSH isopropyl diester by 27%, gamma-glu-cys isopropyl diester
      by 66% and both isopropyl monoesters by over 90% at 120 min. Lung slices and
      tracheal sections incubated with L- or D-CySH at 37 degrees had increased
      cellular concentrations of L- and D-CySH which ranged between 0.88-1.25 nmol mg(
      1) and 1.35-2.25 nmol mg(-1) , respectively. Reducing the incubation temperature
      to 4 degrees had little effect on the accumulation of D-CySH; however, L-CySH
      concentrations increased progressively in the trachea and lung to reach 2.73 and
      2.63 nmol mg(-1) at 90 min, respectively. Lung slices incubated with L- or D-CIPE
      had increased L- or D-CySH concentrations up to a max of 13.7 and 11.1 nmol mg(
      1) and tracheal sections up to a max of 5.56 and 11.09 nmol mg(-1). In the lung
      slice medium, L- and D-CIPE levels had decreased by 75.2% and 74.0% at 90 min,
      respectively, and from the tracheal section medium, L- and D-CIPE concentrations
      had decreased by 66.7% and 32.7%, respectively. Preincubation of lung slices and
      tracheal sections with the carboxylesterase inhibitor, bis (p-nitrophenyl)
      phosphate (BNPP), almost completely prevented the disappearance of L- and D-CIPE
      extracellularly and greatly reduced the appearance of cellular L- and D-CySH.
      GSH, GSH isopropyl diester and gamma-glu-cys isopropyl diester elevated and
      prolonged GSH concentrations in rat lung slices, but GSH isopropyl monoester and
      gamma-glu-cys isopropyl monoester did not increase GSH levels. The uptake of L
      CySH, but not D-CySH, is temperature sensitive in rat lung slices and tracheal
      sections and carboxylesterases appear to have a major influence on the uptake and
      metabolism of L- and D-CIPE by rat lung slices and tracheal sections.

PMID- 9633994
TI  - In vivo radioprotective effects of oltipraz in gamma-irradiated mice.
AB  - Previous studies in this laboratory have shown that oltipraz (Olt), a
      chemopreventive agent, enhances radiation(Rad)-inducible glutathione S
      transferase (GST) and microsomal epoxide hydrolase (mEH) expression in the liver.
      The present study was designed to investigate the in vivo radioprotective effect
      of Olt in ICR mice exposed to a lethal dose of Rad. The 30-day survival rate of
      mice irradiated at the dose of 8 Gy was substantially increased to 91% by Olt
      pretreatment (100 mg/kg/day for 2 days), compared with 48% in animals irradiated
      alone. Light microscopic examinations revealed that exposure of mice to 8 Gy of
      gamma-ray Rad resulted in hepatocyte degeneration in the surviving animals from
      Day 1 through Day 22 after irradiation with certain degrees of necrosis observed
      at early times, whereas Olt treatment provided protection of the liver against
      irradiation with no hepatic necrosis noted. Mice irradiated at the dose of 8 Gy
      exhibited time-related decreases in the white blood cell (WBC), red blood cell
      (RBC), and platelet counts with maximal reduction noted at Day 10. Animals
      irradiated with Olt treatment showed no difference in peripheral blood cell
      counts or in the ratio of myeloid to erythroid bone marrow cells, compared with
      those irradiated alone. Northern RNA blot analysis showed that treatment of mice
      with Olt at the dose of 100 mg/kg in combination with 8 Gy irradiation resulted
      in 12-fold increases in hepatic mEH and mGSTA3 mRNA levels at 24-hr post
      treatment, whereas mGSTP1 mRNA levels were not altered. The mRNA levels for mEH
      and mGSTA3 were elevated after exposure of animals to both Olt and 8 Gy-gamma ray
      to a greater extent than after irradiation alone. The enhanced survival rate
      (91%) in 8 Gy-irradiated animals after treatment with Olt (100 mg/kg/day for 2
      days) was completely reversed by concomitant pretreatment with dexamethasone
      (Dexa) (0.1 and 1 mg/kg/day for 2 days), a known inhibitor of mEH and GST
      expression, resulting in a 42% and 28% survival rate, respectively. Mice
      irradiated after dexamethasone treatment at a dose of 1 mg/kg showed a reduced
      mean survival time compared with those treated with 0.1 mg/kg of dexamethasone (9
      vs 14 days). The current study demonstrates that Olt is effective in increasing
      the survival rate of mice against ionizing Rad and that protective effects of Olt
      associated with enhanced expression of mEH and GST genes may represent its
      radioprotective efficacy.

PMID- 9633995
TI  - Effects of iodotyrosines, thyronines, iodothyroacetic acids and thyromimetic
      analogues on in vitro copper-induced oxidation of low-density lipoproteins.
AB  - We studied the effect of different thyroid compounds [(I2, monoiodo-L-tyrosine
      (MIT), diiodo-L-tyrosine (DIT), L-thyronine (T0), 3,5-diiodo-L-thyronine (T2),
      3,5,3'-triiodo-L-thyronine (T3), 3,3',5'-triiodo-L-thyronine (rT3), 3,5,3',5'
      tetraiodo-L-thyronine (T4), 3,5-diiodothyroacetic acid (TA2), 3,5,3'
      triiodothyroacetic acid (TA3) and 3,5,3',5'-tetraiodothyroacetic acid (TA4)] or
      thyromimetics [(3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT) and 3,5-diiodo-3'
      isopropyl-thyroacetic acid (IpTA2)] on in vitro copper-induced oxidation of low
      density lipoproteins (LDL). Human native LDL (0.05 g protein/L) oxidation was
      induced by 2.5 micromol/L of CuCl2. Conjugated dienes were measured
      spectrophotometrically for up to 10 hr. The length of the lag phase (Tlag),
      maximum velocity of the reaction (Vmax) and the maximum amount of generated
      dienes were obtained from kinetic data. T3 increased Tlag and decreased Vmax with
      a dependence upon concentration (0 to 3 micromol/L). There was no difference
      between the Dmax obtained with Cu2+ alone or in the presence of the various
      compounds (1 micromol/L). I2, MIT and DIT did not modify any parameter of the
      oxidation kinetic. T0 and T2 had the same antioxidant efficiency as T3, whereas
      T4 only decreased Vmax. rT3 increased Tlag less than did T3, whereas DIMIT was
      the thyronine that had the most important effect. TA2 and TA, were the most
      efficient antioxidant compounds. TA4 decreased Tlag less than TA3 did, whereas
      IpTA2 had an effect weaker than that of the physiological acetic derivatives. The
      data suggest that thyroid hormones and derivatives have LDL-antioxidant
      properties, their importance being related to their 4'-hydroxy diphenyl ether
      structure and depending upon the nature and the position of substituents in this
      structure.

PMID- 9633996
TI  - Differential effects of monensin on asialoglycoprotein receptor function after
      short-term ethanol administration.
AB  - Chronic ethanol consumption is associated with multiple impairments in receptor
      mediated endocytosis (RME) by the hepatic asialoglycoprotein receptor (ASGP-R).
      Previous work on this receptor has shown that its activity can be perturbed by
      the carboxylic ionophore monensin. This agent has been shown to preferentially
      affect receptor-ligand dissociation and receptor redistribution of one subset
      (State 2) of ASGP-R, while receptor function in a second subset (State 1
      receptors) is unaffected. In the present study, we examined the effect of
      monensin on ASGP-R activity and intracellular receptor-ligand dissociation after
      7-10 days of ethanol feeding, a time when we have shown altered ASGP-R function
      in ethanol-fed animals. Hepatocytes from male Wistar rats (fed an ethanol
      containing or control diet) were utilized. Ethanol administration decreased total
      ligand binding by 35-40% (P < 0.01) without a change in receptor protein content.
      After monensin treatment, surface receptors on cells from control animals were
      inactivated and redistributed to the cell interior. In cells from ethanol-fed
      animals, a similar pattern of monensin-induced inactivation was shown, but no
      redistribution occurred. Intracellular receptor-ligand dissociation was impaired
      in both cell types, although the monensin-induced effect on dissociation was
      significantly less dramatic (two-fold) in the hepatocytes from ethanol-fed
      animals as compared with controls. Thus, although receptors on both cell types
      were susceptible to monensin, cells from the ethanol-fed animals were less
      vulnerable to the added effects of this agent. Since monensin affects functioning
      of State 2, but not State 1 receptors, a very early effect of ethanol may be a
      preferential impairment in the State 2 receptor population.

PMID- 9633997
TI  - 19F NMR study of the uptake of 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil
      in erythrocytes: evidence of transport by facilitated and nonfacilitated
      pathways.
AB  - The 19F NMR resonances of intra- and extracellular 2'-fluoro-5-methyl-beta-L
      arabinofuranosyluracil (L-FMAU) in suspensions of human erythrocytes are well
      resolved. This phenomenon allows its transport behavior to be monitored in a 19F
      NMR time-course experiment. The rate of L-FMAU uptake at 25 degrees in a
      suspension containing L-FMAU at an initial extracellular concentration of 4 mM
      was 7.6 +/- 1.0 x 10(-7) pmol cell(-1) sec(-1) (N = 5). Concentration-dependent
      uptake studies of L-FMAU indicate the existence of both saturable and
      nonsaturable transport mechanisms, with a Km for the saturable uptake of
      approximately 1 mM. Although the transport of L-FMAU at 25 degrees was inhibited
      significantly (54-65%) by nitrobenzylthioinosine (NBTI) and dipyridamole,
      consistent with the participation of the nucleoside transporter, these inhibitors
      did not achieve complete blockage of L-FMAU uptake. The participation of the
      nucleobase transporter in L-FMAU uptake was ruled out by the absence of
      competition with uracil uptake, and by the lack of inhibition by papaverine. In
      addition, the NBTI-insensitive uptake of L-FMAU was not affected by pretreatment
      of the cells with the sulfhydryl reagent, p-chloromercuriphenylsulfonic acid
      (pCMBS). However, the NBTI- and dipyridamole-insensitive transport of L-FMAU was
      found to increase upon treatment of the erythrocytes with butanol, an agent that
      affects membrane fluidity. The partition coefficient of L-FMAU in
      octanol/phosphate-buffered saline determined by absorption spectrophotometry was
      0.31. These data indicate that under the conditions of the studies, L-FMAU uptake
      by erythrocytes proceeds by both the nucleoside transporter and nonfacilitated
      membrane diffusion.

PMID- 9633998
TI  - Regulation of cyclo-oxygenase gene expression in rat smooth muscle cells by
      catalase.
AB  - We have studied, in detail, the effect of catalase, one of the naturally
      occurring antioxidant enzymes, on the expression of cyclo-oxygenase (COX) mRNA
      and protein in rat aortic smooth muscle cells (RASMC). The activity of COX enzyme
      within the cells was also determined. Catalase either alone or in combination
      with interleukin-1beta (IL-1beta) enhanced mRNA and protein expression for cyclo
      oxygenase 2 (COX-2) in a concentration-dependent manner. However, it did not
      affect the expression of mRNA or protein for cyclo-oxygenase 1 (COX-1). The
      expression of mRNA for COX-2 induced by catalase was blocked completely by
      actinomycin D (ACT) or cycloheximide (CHX). In comparison, expression of mRNA for
      COX-2 stimulated by IL-1beta was inhibited by actinomycin D, but not by
      cycloheximide. This suggests that induction of the synthesis of mRNA for COX-2 by
      catalase and IL-1beta involves different mechanisms. In particular, the induction
      of mRNA for COX-2 by catalase requires on-going protein and RNA synthesis, but
      the induction following exposure to IL-1beta does not. The increase in expression
      of mRNA for COX-2 induced by catalase may be related to the ability of catalase
      to stimulate cyclic AMP response element (CRE) and NF-IL6 transcription factors,
      but not nuclear factor kappa B (NF-kappaB), for electrophoretic mobility shift
      assays (EMSA) showed that catalase enhanced nuclear factor binding to cyclic AMP
      response element and NF-IL6 but not to NF-kappaB. Catalase exerted a biphasic
      effect on prostaglandin synthesis. At low concentrations it enhanced
      prostaglandin production, but at high concentrations it tended to inhibit it.
      These findings suggest that catalase has differential and multiple effects on COX
      expression and activity in rat aortic smooth muscle cells.

PMID- 9633999
TI  - Inhibitory monoclonal antibody to human cytochrome P450 2B6.
AB  - The human cytochrome P450 2B6 metabolizes, among numerous other substrates,
      diazepam, 7-ethoxycoumarin, testosterone, and phenanthrene. A recombinant
      baculovirus containing the human 2B6 cDNA was constructed and used to express 2B6
      in Sf9 insect cells. The 2B6 was present at 1.8 +/- 0.4% of the total cellular
      protein and was purified to a specific content of 13.3 nmol/mg protein. Mice were
      immunized with the purified 2B6, and a total of 811 hybridomas were obtained from
      the fusion of NS-1 myeloma cells and spleen cells of the immunized mice.
      Monoclonal antibodies (MAbs) from 24 of the hybrids exhibited immunobinding to
      2B6 as determined by ELISA. One of the MAbs, 49-10-20, showed a strong
      immunoblotting activity and was highly inhibitory to 2B6 enzyme activity. MAb 49
      10-20 inhibited cDNA-expressed 2B6-catalyzed metabolism of diazepam,
      phenanthrene, 7-ethoxycoumarin, and testosterone by 90-91%. MAb 49-10-20 showed
      extremely high specificity for 2B6 and did not bind to 17 other human and rodent
      P450s or inhibit the metabolism of phenanthrene catalyzed by human 1A2, 2A6, 2C8,
      2C9, 2D6, 2E1, 3A4, and 3A5. MAb 49-10-20 was used to determine the contribution
      of 2B6 to the metabolism of phenanthrene and diazepam in human liver. In ten
      liver samples, MAb 49-10-20 inhibited phenanthrene metabolism variably by a wide
      range of 8-42% and diazepam demethylation by 1-23%. The degree of inhibition by
      the 2B6 specific MAb 49-10-20 defines the contribution of 2B6 to phenanthrene and
      diazepam metabolism in each human liver. This technique using inhibitory MAb 49
      10-20 determines the contribution of 2B6 to the metabolism of its substrates in a
      human tissue containing multiple P450s. This study is a prototype for the use of
      specific and highly inhibitory MAbs to determine individual P450 function.

PMID- 9634000
TI  - Increased concentrations of methylated 6-mercaptopurine metabolites and 6
      thioguanine nucleotides in human leukemic cells in vitro by methotrexate.
AB  - The effect of methotrexate (MTX) on 6-mercaptopurine (6-MP) metabolism was
      studied in four human leukemic cell lines in vitro. CCRF-CEM, WI-L2, TBJ, and HL
      60 all expressed thiopurine methyltransferase (TPMT) activity. The cells were
      grown in horse serum-supplemented RPMI 1640 medium to which was added 4 microM of
      6-MP or 4 microM of 6-MP and 20 nM of MTX. The presence of MTX resulted in a 2.1
      , 1.7-, 2.4- and 8-fold increase in the concentrations of methylmercaptopurine
      ribonucleotides (MMPRP) in CEM, WI-L2, TBJ, and HL-60 cells, respectively (P <
      0.0008). The concentrations of 6-thioguanine nucleotides (6 TGN) increased 1.9-,
      1.4-, 2.4- and 1.9-fold in the same cell lines (P < 0.02). The four cell lines
      differed with respect to the effect of MTX on the consumption of 6-MP from the
      medium; CEM consumed more 6-MP and WI-L2 less 6-MP from media containing MTX than
      from media containing 6-MP only (P = 0.005 and 0.02, respectively). MTX did not
      affect the consumption of 6-MP by TBJ cells (P = 0.17). Media in which HL-60
      cells had been grown did not contain detectable amounts of 6-MP at the end of the
      experiment. The simultaneous increase in methylated 6-MP metabolites and 6-TGN
      represents a possible explanation for the synergism of MTX and 6-MP; however, the
      clinical importance of increased MMPRP remains to be elucidated.

PMID- 9634001
TI  - Suppression of C/EBPalpha and induction of C/EBPbeta by 2,3,7,8
      tetrachlorodibenzo-p-dioxin in mouse adipose tissue and liver.
AB  - We examined the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on two
      transcription factors, CAAT/enhancer binding protein-alpha (C/EBPalpha) and beta
      (C/EBPbeta), involved in the coordination of gene expression in adipose and
      liver. A single dose of TCDD (100 microg/kg) to male C57BL mice resulted in a
      time- and dose-dependent decrease in the level of C/EBPalpha mRNA in adipose
      tissue and liver, and a reciprocal increase in C/EBPbeta mRNA. Gel shift analysis
      using hepatic nuclear extracts from control and TCDD-treated mice and an
      oligonucleotide containing a C/EBP recognition element revealed a time-dependent
      change in DNA-protein complexes formed. Bands corresponding to C/EBPalpha, as
      determined by supershift analysis, diminished in TCDD-treated animals over a 7
      day time period, whereas two new bands corresponding to C/EBPbeta, not present in
      control extracts, were increased significantly in treated samples. TCDD induced
      C/EBPbeta mRNA in wild-type mouse hepatoma cells, but not in aryl hydrocarbon
      receptor (AhR) nuclear translocator-deficient hepatoma cells. Induction in wild
      type hepatoma cells was antagonized effectively by a molar excess of alpha
      naphthoflavone. These results showed that TCDD caused rapid, reciprocal changes
      in C/EBPalpha and C/EBPbeta mRNAs and DNA binding in the adipose and liver of
      male C57BL mice and induced C/EBPbeta in hepatoma cells in an AhR-dependent
      manner. C/EBPs play vital roles in the coordination of energy homeostasis, and
      their alteration by TCDD may provide insight into the mechanism by which TCDD
      perturbs energy storage and utilization in vivo.

PMID- 9634002
TI  - Determination of deoxyribonucleoside triphosphate pool sizes in ribonucleotide
      reductase cDNA transfected human KB cells.
AB  - Ribonucleotide reductase (RR) is a rate-limiting enzyme in DNA synthesis, which
      is responsible for controlling deoxyribonucleoside triphosphate (dNTP) pool size.
      It has been shown that transfection of RR M2 cDNA in human KB cells (M2-D clone)
      results in overexpression for the M2 subunit and resistance to hydroxyurea (HU).
      In this study, dNTP pool assays were performed to measure the pool sizes in six
      cell lines: two controls, three transfectants, and drug-induced HU-resistant
      (HUR) cells. Total dNTP levels among the six cell lines rose in the following
      order: KB wild-type, KB vector-only transfectant, M1 cDNA transfectant, M2 cDNA
      transfectant, M1/M2 cDNA transfectant, and HU-induced resistant clone. The dCTP
      levels of the cells mimicked the total dNTP pools on a smaller scale. The
      significant increases in the dCTP pool sizes of the M2-D, X-D, and HUR clones
      were proportional to their respective increases in RR activity. Relative to all
      other transfectants, the M1-D clone demonstrated lower dCTP levels but increased
      dATP pools. The M1-D clone demonstrated a significant resistance to dNTP
      inhibition of RR activity compared with the control KB wild-type cells. In
      contrast, a profound inhibition of dCTP and a decreased sensitivity to dATP
      inhibition was observed in M2-D, X-D, and HUR clones. In summary, M2 cDNA
      transfectants and HUR clones had increased RR activity as well as expanded dNTP
      pools, particularly dCTP, when compared with wild-type KB cells. These data
      provide evidence for the intertwined relationship between RR activity and dNTP
      pools.

PMID- 9634003
TI  - In vivo formation of a Schiff base of aminoguanidine with pyridoxal phosphate.
AB  - Aminoguanidine (AG) is considered to be a promising compound for the treatment of
      diabetic complications. We examined the in vitro and in vivo formation of Schiff
      bases of AG with pyridoxal 5'-phosphate (PLP) and pyridoxal (PL). AG reacted in
      vitro far more rapidly with PLP to form a Schiff base (PLP-AG) than with PL to
      form another Schiff base (PL-AG). Administration of AG at 7 mM in drinking water
      for 18 weeks caused the formation of PLP-AG in the liver and kidney of mice (12.1
      +/- 1.6 and 3.8 +/- 0.64 nmol/g of tissue, respectively, mean +/- SD, N = 6). The
      amount of PLP in the liver of mice AG administered was significantly lower than
      that of control mice (4.0 +/- 1.4 vs 17.4 +/- 1.3 nmol/g of wet tissue, mean +/-
      SD, N = 6). Simultaneous administration of pyridoxine (1 mM in drinking water)
      with AG (7 mM in drinking water) did not ameliorate the decrease in tissue PLP
      and caused the excess formation of PLP-AG. The results suggest that attention
      should be paid to the deficiency of tissue PLP in the clinical use of AG.

PMID- 9634004
TI  - Metabolism and metabolic actions of 6-methylpurine and 2-fluoroadenine in human
      cells.
AB  - Activation of purine nucleoside analogs by Escherichia coli purine nucleoside
      phosphorylase (PNP) is being evaluated as a suicide gene therapy strategy for the
      treatment of cancer. Because the mechanisms of action of two toxic purine bases,
      6-methylpurine (MeP) and 2-fluoroadenine (F-Ade), that are generated by this
      approach are poorly understood, mechanistic studies were initiated to learn how
      these compounds differ from agents that are being used currently. The
      concentration of F-Ade, MeP, or 5-fluorouracil required to inhibit CEM cell
      growth by 50% after a 4-hr incubation was 0.15, 9, or 120 microM, respectively. F
      Ade and MeP were also toxic to quiescent MRC-5, CEM, and Balb 3T3 cells.
      Treatment of CEM, MRC-5, or Balb 3T3 cells with either F-Ade or MeP resulted in
      the inhibition of protein, RNA, and DNA syntheses. CEM cells converted F-Ade and
      MeP to F-ATP and MeP-ribonucleoside triphosphate (MeP-R-TP), respectively. The
      half-life for disappearance of HeP-ribonucleoside triphosphate from CEM cells was
      approximately 48 hr, whereas the half-lives of F-ATP and ATP were approximately 5
      hr. Both MeP and F-Ade were incorporated into the RNA and DNA of CEM cells. These
      studies indicated that the mechanisms of action of F-Ade and MeP were quite
      different from those of other anticancer agents, and suggested that the
      generation of these agents in tumor cells by E. coli PNP could result in
      significant advantages over those generated by either herpes simplex virus
      thymidine kinase or E. coli cytosine deaminase. These advantages include a novel
      mechanism of action resulting in toxicity to nonproliferating and proliferating
      tumor cells and the high potency of these agents during short-term treatment.

PMID- 9634005
TI  - Concentrating capacity of the human reduced folate carrier (hRFC1) in human ZR-75
      breast cancer cell lines.
AB  - Human RFC1 (hRFC1) transfected in transport-deficient methotrexate MTXR(R)ZR-75-1
      human breast carcinoma cells (MTX(R)ZR-75/RFC) were used to investigate the
      impact of hRFC1 overexpression on influx and concentrative transport of
      methotrexate (MTX). Eight-fold overexpression of hRFC1, as determined by northern
      analysis, resulted in a 4-fold increase in MTX influx accompanied by a 2.4-fold
      increase in the steady-state level of free drug as compared with wild-type ZR-75
      1 cells when the extracellular MTX level was 0.5 microM. When extracellular MTX
      was increased to 10 microM, the increase in influx equaled the increase in the
      transmembrane chemical gradient for MTX in the transfectant relative to wild-type
      cells. By 50 min, approximately 16-20 and 25% of the intracellular 3H represented
      MTX polyglutamates by HPLC analysis at [MTX]e = 0.5 and 10 microM in wild-type
      and transfected cells, respectively. Overexpression of hRFC1 enhanced sensitivity
      to MTX in MTX(R)ZR-75-1 cells by more than 250-fold. The data indicate that
      overexpression of hRFC1 in human cells results in comparable increases in influx
      and transmembrane gradients. This is different from what was reported when mouse
      RFC1 was transfected into murine leukemia cells, resulting in large, more
      symmetrical increases in the MTX bidirectional transport kinetics with a much
      smaller change in steady-state levels. The changes in the human cells transfected
      with hRFC1 however, were similar to what has been observed by other investigators
      when RFC1 expression is increased by low folate selective pressure.

PMID- 9634006
TI  - Stimulation of melanogenesis in a human melanoma cell line by bistratene A.
AB  - The polyether toxin, bistratene A, induced morphological and functional
      differentiation of a human melanoma cell line (MM96E). The cells became blocked
      at the G2/M transition and elaborated a number of processes. Tyrosinase activity
      and melanin content were substantially increased. Northern blot analysis showed
      up-regulation of mRNA for several genes known to be involved in melanin
      biosynthesis (pmel17, pmel34, and tyrosinase related proteins, TRP-1 and TRP-2).
      Bistratene A induced the phosphorylation of several proteins as assessed by 2D
      gel electrophoresis and one of these was identified as stathmin (oncoprotein 18),
      a cell-cycle regulated phosphoprotein. Bistratene A specifically induced the
      translocation of protein kinase Cdelta (PKCdelta) from a soluble to a particulate
      fraction without affecting other isoforms. These results implicate a role for
      protein kinase Cdelta in the induction of differentiation of this human melanoma
      cell line.

PMID- 9634007
TI  - O6-alkylguanine-DNA alkyltransferase inactivation by ester prodrugs of O6
      benzylguanine derivatives and their rate of hydrolysis by cellular esterases.
AB  - To modulate the bioavailability and perhaps improve the tumor cell selectivity of
      O6-alkylguanine-DNA alkyltransferase (AGT) inactivators, pivaloyloxymethyl ester
      derivatives of O6-benzylguanine (BG) were synthesized and tested as AGT
      inactivators and as substrates for cellular esterases. The potential prodrugs
      examined were the 7- and 9-pivaloyloxymethyl derivatives of O6-benzylguanine (7-
      and 9-esterBG), and of 8-aza-O6-benzylguanine (8-aza-7-esterBG and 8-aza-9
      esterBG) and the 9-pivaloyloxymethyl derivative of 8-bromo-O6-benzylguanine (8
      bromo-9-esterBG). The benzylated purines were all potent inactivators of the pure
      AGT and of the AGT activity in HT29 cells and cell extracts. Each ester was at
      least 75 times less potent than the corresponding benzylated purine against the
      pure human AGT. In contrast, the activities of esters and their respective
      benzylated purine were similar in crude cell extracts and in intact cells. The
      increase in potency of esters in cellular extracts could be explained by a
      conversion of the respective prodrug to the more potent benzylated purine in the
      presence of cellular esterases. The apparent catalytic activity (Vmax/Km) of
      liver microsomal esterase for 8-azaBG ester prodrugs was 70-130 times greater
      than for BG prodrugs and 10-20 times greater than for 8-bromo-9-esterBG. Tumor
      cell hydrolysis of the esters varied considerably as a function of cell type and
      prodrug structure. These data suggest that these or related prodrugs may be
      advantageous for selective AGT inactivation in certain tumor types.

PMID- 9634008
TI  - Induction of apoptosis in glioblastoma cells by inhibition of protein kinase C
      and its association with the rapid accumulation of p53 and induction of the
      insulin-like growth factor-1-binding protein-3.
AB  - Increased protein kinase C(alpha) (PKC(alpha)) expression in glioblastoma cells
      is associated with proliferation and resistance to drug-induced apoptosis by an
      undefined anti-apoptotic pathway. To clarify the role of PKC in apoptosis, we
      have investigated the effect of the selective PKC inhibitor Ro 31-8220 (3-[1-[3
      (amidinothio)propyl]-3-indolyl]-4-(1-methyl-3-indolyl)-1H -pyrrole-2,5-dione
      methanesulfonate) in two glioblastoma cell lines whose proliferation is dependent
      on high levels of PKC(alpha). U-87 and A172 cells treated with an IC50 of Ro 31
      8220 exhibited nucleosomal DNA fragmentation that coincided with an increase in
      the number of apoptotic cells. This effect was preceded by the rapid nuclear
      accumulation of wild-type p53 within 2 hr, and an increased level of the pro
      apoptotic protein, insulin-like growth factor-1-binding protein-3, (IGFBP3) but
      not other p53-regulated proteins such as p21WAF1 or Bax. Accumulation of p53 was
      also associated with the hypophosphorylated and activated form of the
      retinoblastoma tumor suppressor protein (RB) at later times after treatment.
      These results suggest that PKC(alpha) suppresses apoptosis in glioblastoma cells
      primarily by restricting the accumulation of p53 and the expression of insulin
      like growth factor-1-binding protein, as well as by maintaining RB in an inactive
      hyperphosphorylated state.

PMID- 9634009
TI  - Transport of quercetin and its glucosides across human intestinal epithelial Caco
      2 cells.
AB  - There is mounting evidence from human epidemiological, animal in vivo, and in
      vitro studies to suggest beneficial effects related to the consumption of
      quercetin and its glucosides. However, there is limited knowledge on the oral
      bioavailability of these natural products. This study examined the intestinal
      epithelial membrane transport of quercetin, quercetin 4'-glucoside, and quercetin
      3,4'-diglucoside, using the Caco-2 human colonic cell line, a model of human
      intestinal absorption. The apparent permeability (Papp) of each agent was
      measured in both apical to basal and basal to apical directions. The apical to
      basolateral flux of quercetin, Papp 5.8 +/- 1.1 x 10(-6) cm x sec(-1) (mean +/-
      SEM), was more than 10-fold higher than for the paracellular transport marker
      mannitol, 0.48 +/- 0.09 x 10(-6) cm x sec(-1) (P < 0.01). Under identical
      conditions, the Papp for the transcellular marker propranolol was about 5-fold
      higher than for quercetin (P < 0.001). Interestingly, the reverse, basolateral to
      apical, flux of quercetin (Papp 11.1 +/- 1.2 x 10(-6) cm x sec(-1)) was almost 2
      fold higher than the apical to basolateral flux (P < 0.001). In similar
      experiments, quercetin 4'-glucoside demonstrated no absorption, Papp < 0.02 x 10(
      6) cm x sec(-1) in the apical to basal direction, but did demonstrate basal to
      apical flux, Papp 1.6 +/- 0.2 x 10(-6) cm x sec(-1). Quercetin 3,4'-diglucoside
      showed a low apical to basolateral transport (Papp 0.09 +/- 0.03 x 10(-6) cm x
      sec(-1)); its reverse, basolateral to apical, transport was, however, 4-fold
      higher (P < 0.05). In these cells, glucose was actively transported with an
      apical to basolateral Papp of 36.8 +/- 1.1 x 10(-6) cm x sec(-1). These
      observations suggest facile absorption of quercetin through the human intestinal
      epithelium, but contrary to a previous proposal, they do not support an active
      transport process for quercetin glucosides.

PMID- 9634010
TI  - Gene-dose effect on carnitine transport activity in embryonic fibroblasts of JVS
      mice as a model of human carnitine transporter deficiency.
AB  - Recently, the marked decline in renal carnitine reabsorption has been thought to
      account fotr the systemic carnitine deficiency in juvenile visceral steatosis
      (JVS) mice. We have conducted a kinetic analysis using embryonic fibroblasts
      derived from normal, heterozygous, and homozygous jvs mice and found that the
      high-affinity carnitine transporter (Km = 5.5 microM), which shows Na+ and
      temperature dependency and stereospecificity, is defective in homozygous jvs
      mice. Moreover, a gene dose-dependent decrease of carnitine transport activity,
      which was due to a decrease in the number of the transporter molecules, was found
      in heterozygous jvs mice. Similar phenomena have been observed in human primary
      carnitine deficiency. Therefore, JVS mice may be useful for understanding this
      extremely rare human hereditary disorder.

PMID- 9634011
TI  - Inhibition of cholinesterase-associated aryl acylamidase activity by
      anticholinesterase agents: focus on drugs potentially effective in Alzheimer's
      disease.
AB  - The potency of a series of anticholinesterase (anti-ChE) agents and serotonin
      related amines as inhibitors of the aryl acylamidase (AAA) activity associated
      with electric eel acetylcholinesterase (AChE) (EC 3.1.1.7) and horse serum
      butyrylcholinesterase (BuChE) (EC 3.1.1.8) was examined and compared with the
      potency of the same compounds as ChE inhibitors. Neostigmine, physostigmine, BW
      284C51, (+/-)-huperzine A, E2020, tacrine, edrophonium and heptyl-physostigmine
      were, in that order, the most potent in inhibiting eel AChE-associated AAA
      activity, their inhibitor constant (Ki) values being in the range 0.02-0.37
      microM. The rank order of the same compounds as AChE inhibitors basically
      paralleled that of AAA, although they were in general stronger on AChE (Ki =
      0.001-0.05). The peripheral anionic site inhibitors propidium and gallamine were
      inactive on AChE-associated AAA. Serotonin and its derivatives were slightly
      stronger on AAA (Ki = 7.5-30 microM) than on AChE (Ki = 20-140 microM). Tacrine
      (IC50 = 0.03 microM), diisopropylfluorophosphate (IC50 = 0.04 microM), heptyl
      physostigmine (IC50 = 0.11 microM), physostigmine (IC50 = 0.15 microM) and tetra
      iso-propylpyrophosphoramide (iso-OMPA) (IC50 = 0.75 microM) were the most potent
      in inhibiting horse serum BuChE-associated AAA activity. Serotonin and related
      amines were very weak on BuChE-associated AAA activity. These results indicate
      that the inhibitory potencies of the active site anti-ChE agents on the AAA
      activity associated with eel AChE and horse serum BuChE are closely correlated
      with their action on the respective ChE. In addition, the efficacy of tacrine,
      E2020, heptyl-physostigmine and (+/-)-huperzine A in the treatment of Alzheimer's
      disease is unlikely to be related to the action of these drugs on ChE-associated
      AAA.

PMID- 9634012
TI  - Standardization and definitions in lower urinary tract dysfunction in children.
      International Children's Continence Society.

PMID- 9634013
TI  - Desmopressin in the treatment of severe nocturnal enuresis in adolescents--a 7
      year follow-up study.
AB  - OBJECTIVES: To evaluate the role of long-term oral desmopressin (over a 7-year
      follow-up) in refractory enuretics, particularly in assessing the potential
      curative effect, and to analyse the results for specific types of patient to
      obtain clues about possible mechanisms of cure. PATIENTS AND METHODS: The effect
      of oral desmopressin was investigated in 25 adolescents (aged 11-21 years) with
      severe monosymptomatic nocturnal enuresis. The long-term study consisted of two
      12-week treatment periods, with the efficacy of the drug assessed as the
      reduction in the number of wet nights per week. Subsequently, the patients were
      followed-up for up to 7 years. Close contact was maintained with the families
      over this period ('good doctoring' approach). At 3-, 5- and 7-year intervals
      after completing the study, patients were assessed for dryness, frequency,
      treatment and sleeping habits, using postal questionnaires and telephone follow
      up. RESULTS: At the end of the long-term study, 35% of the patients remained dry
      without therapy. Within 2 years of ending treatment, 15 patients were dry,
      compared with an expected estimate of six by spontaneous resolution, and after 7
      years, 19 patients were cured. Nocturia occurred in 75% of the enuretic patients
      but in only 5% of the healthy controls. CONCLUSIONS: Active treatment of primary
      nocturnal enuresis with oral desmopressin has a clinically significant effect on
      the cure rate, which is maintained after ceasing therapy. The cure rate was
      higher than would be expected from spontaneous recovery alone during the first 2
      years of the study and there was a significant further increase in the cure rate
      7 years after ending therapy, again greater than the expected spontaneous cure
      rate. There also seemed to be a better response to treatment when it was
      prolonged. Furthermore, this therapy is safe when administered in the long-term.

PMID- 9634014
TI  - Long-term use and tapered dose reduction of intranasal desmopressin in the
      treatment of enuretic children.
AB  - OBJECTIVE: To determine the time taken to achieve complete dryness, the
      management of desmopressin dosage to reduce the relapse rate, the mean dosage in
      those responding and any side effects of long-term treatment. PATIENTS AND
      METHODS: Enuretic children (155, 68% boys and 32% girls, mean age 8 years, range
      5-19) were treated with desmopressin and assessed. Treatment (intranasal spray)
      was started with 20 microg desmopressin and titrated to 40 microg (maximum 50
      microg) after 2 days if the child did not become dry within 48 h. The maximum
      dosage was maintained for at least 4-6 weeks. After 4 weeks of complete dryness,
      the dosage was reduced by 10 microg initially, and after each additional 4 dry
      weeks, by a further 10 microg; medication was stopped only after 4 dry weeks at
      10 microg. RESULTS: Of the children, 85% responded to intranasal desmopressin
      therapy; 71% achieved complete dryness with no relapses, remaining dry with no
      further treatment, 7% achieved dryness after relapses during or after therapy, 7%
      improved (no more than two wet nights per week) and 15% did not respond to
      therapy or improved only slightly (> 2 wet nights per week). The mean duration of
      therapy was 28 weeks, the mean dose of desmopressin was 30 microg and the median
      follow-up 18 months. There were no significant side-effects. CONCLUSION: This
      study indicates that rapid titration until dryness within 1-3 days, a long
      maintenance therapy of at least 4-6 weeks and a slow stepwise reduction of dose
      decreases the frequency of relapse and improves the outcome.

PMID- 9634015
TI  - Combination therapy in the treatment of persistent nocturnal enuresis.
AB  - OBJECTIVE: To evaluate, in a retrospective study, the response rate of older
      children to combination therapy using a sustained-release anticholinergic agent,
      hyoscyamine, and a synthetic analogue of antidiuretic hormone, desmopressin
      acetate. PATIENTS AND METHOD: Twenty-eight patients (20 males and eight females,
      aged 9-18 years) diagnosed with nocturnal enuresis were evaluated using a
      questionnaire, history and physical examination. None had success with single
      agent pharmacological therapy. All were begun on 0.375 mg of hyoscyamine and 20
      microg of desmopressin intranasally at bedtime. The response rate was monitored
      at 2 and 4 weeks, and then every 3 months by recording dry nights on a calendar.
      To improve efficacy, the dosage of medication was adjusted up to 0.750 mg of
      hyoscyamine and 60 microg of desmopressin. Upon achieving dryness and spontaneous
      awakening to void, medication doses were tapered. RESULTS: Within 6 months 16
      (57%) patients were completely dry and six (21%) were dry at least 80% of nights.
      Nine patients relapsed during dose tapering and therapy was reinstituted.
      Presently, 17 (60%) patients are off medication (after a mean of 8 months of
      medication). Eight patients are still on medication and are dry at least 80% of
      nights. Combination therapy failed in three patients and they have transferred to
      a different regimen. None experienced untoward side-effects from the medications.
      CONCLUSION: Most older children with nocturnal enuresis responded to combination
      therapy. These children require long-term follow-up and may need medication for
      up to 6 months because the relapse rate is fairly high. Combination therapy
      appears safe and reliable in treating nocturnal enuresis in older children who
      have had no success with other treatment modalities.

PMID- 9634016
TI  - The effectiveness of desmopressin in the treatment of childhood nocturnal
      enuresis: predicting response using pretreatment variables.
AB  - OBJECTIVE: To determine the factors that predict the effectiveness of
      desmopressin in the treatment of childhood nocturnal enuresis. PATIENTS AND
      METHOD: Sixty-six children with monosymptomatic nocturnal enuresis were treated
      with intranasal or oral desmopressin for a 4-week period. starting with a
      standard dose of 20 microg (0.2 mg oral) and increasing after 2 weeks where no
      progress was apparent to 40 microg (0.4 mg oral). Before treatment a range of
      variables (demographic, situational, enuretic history, physiological, parental
      attitude and child) were recorded. Three parameters of success acted as dependent
      variables, with stepwise linear regression models used to determine pretreatment
      predictors of success with desmopressin. RESULT: Each outcome variable produced a
      very similar model of predictors. Success, as assessed by the most dry nights
      over a 14-night period, was associated with less severe enuresis before
      treatment, a parental belief that the child's enuresis was unstable and higher
      birthweight. CONCLUSION: From the analysis, a model of arginine vasopressin
      release is proposed and the clinical implications of the findings addressed.

PMID- 9634017
TI  - Molecular genetic, clinical and psychiatric associations in nocturnal enuresis.

PMID- 9634018
TI  - Persistent enuresis caused by nocturnal polyuria is a maturation defect of the
      nyctihemeral rhythm of diuresis.

PMID- 9634019
TI  - Monosymptomatic primary enuresis: differences between patients responding or not
      responding to oral desmopressin.
AB  - OBJECTIVES: To evaluate the 24-h diuresis, urinary osmolality, plasma arginine
      vasopressin (AVP) and urinary prostaglandin E2 (PGE2) before and during
      desmopressin treatment in patients with monosymptomatic primary enuresis (MPE),
      and to investigate the possible depressor effect of desmopressin on the detrusor
      in such patients with urodynamically confirmed bladder instability. PATIENTS AND
      METHODS: Seven healthy children (control group) and 11 consecutive patients with
      MPE (mean age 10.4 years, range 7-15) were assessed using laboratory tests, renal
      and bladder ultrasonography, and video-urodynamic investigations. A 24-h
      inpatient assessment with a controlled water intake of 20 mL/kg per day included
      determinations of diuresis, urinary osmolality, AVP and PGE2 in both normal
      children and those with MPE. After 30 days of treatment at optimal doses of
      desmopressin, all children were hospitalized and re-evaluated during desmopressin
      treatment; all completed 3 months of treatment at optimal doses. At the end of
      this period, patients whose symptoms improved by > or = 80% were defined as
      'responders' while those in whom they did not were defined as 'non-responders'.
      RESULTS: After treatment, six of the 11 patients with MPE were 'responders' and
      five 'non-responders'. Urodynamic evaluation showed bladder instability in seven
      of the 11 patients with MPE but in those with bladder dysfunction, urodynamic
      studies carried out during desmopressin treatment showed no changes in detrusor
      activity. There were significant differences in the morning values of AVP between
      normal children and responders (P < 0.03), and between responders and non
      responders (P < 0.02); none of the non-responders had AVP levels of < 2.5 pg/mL,
      while none of the responders exceeded this value. At midnight, responders had the
      lowest mean AVP and non-responders the highest; this correlated with the highest
      PGE2 value in the nonresponders at 00.00-08.00 hours. Non-responders had an
      overnight mean PGE2 level greater than that in normal subjects or responders.
      CONCLUSIONS: Polyuria occurred in all patients with MPE, independently of the
      response to desmopressin. Responders had the lowest AVP values over the 24 h; the
      morning AVP levels differentiated normal subjects from enuretic patients and
      responders from non-responders. In patients with MPE, clinically undetected
      bladder instability was unrelated to the results of treatment and there were no
      urodynamic changes during desmopressin treatment. The differences between
      enuretic patients suggested a different aetiology of MPE, probably related to an
      increase in PGE2 concentration and an antagonistic mechanism of action of AVP or
      desmopressin.

PMID- 9634020
TI  - Primary enuresis: a urodynamic evaluation.
AB  - OBJECTIVE: To assess urodynamic and clinical data in patients with primary
      enuresis for potential prognostic indicators of detrusor instability. PATIENTS
      AND METHODS: The records of 33 patients (mean age 8.8 years, range 5-14) with
      monosymptomatic primary enuresis (MPE, bedwetting as the sole symptom) and 47
      patients (mean age 7.1 years, range 5-12) with complicated primary enuresis (CPE,
      bedwetting associated with diurnal urinary loss, squatting and urge incontinence)
      were reviewed. The children underwent urodynamic studies to detect detrusor
      instability and the prevalence was compared with the type of enuresis. RESULTS:
      Of 33 patients with MPE, 17 (49%) showed either typical unstable detrusor
      contractions (16) or low-compliance bladders (one); in the remaining 16 patients,
      filling cystometry was normal and micturition was normal in all. Of the 47
      patients with CPE, 35 (79%) showed detrusor instability and two decreased bladder
      compliance; the remaining 10 had stable bladders and micturition was also normal
      in all patients. CONCLUSION: The type of primary enuresis and the maximum
      cystometric bladder capacity were good indicators of bladder dysfunction.

PMID- 9634021
TI  - Evaluation of antidiuretic hormone before and after long-term treatment with
      desmopressin in a group of enuretic children.
AB  - OBJECTIVE: To determine the effect of long-term desmopressin therapy in enuretic
      patients on the levels of antidiuretic hormone (ADH) during and after the end of
      therapy. PATIENTS AND METHODS: The study comprised 25 outpatients (18 boys and
      seven girls) aged 8-12 years at the start of therapy and 12-16 years at the end.
      The morning (08.00 hours) plasma ADH level was determined before treatment (T0)
      with desmopressin and 2 years after (T1) ending the therapy. Seven of the 25
      patients evaluated had monosymptomatic (simple enuresis, SE) and 18 had other
      symptoms (complex enuresis, CE). RESULTS: In the patients with SE, the mean (SD)
      duration of therapy was 305 (183) days and they were reevaluated 2.5 (0.67) years
      later. Of 18 patients with CE, eight were treated only with desmopressin for 204
      (117) days. In 10 with an incomplete response after 30 days with only
      desmopressin, oxybutynin (5 mg twice daily) was added; the duration of their
      therapy was 255 (152) days and they were re-evaluated 3.9 (0.6) years later. The
      mean (SD) ADH level in those with SE and CE was 2.14 (0.93) ng/L and 2.53 (1.16)
      ng/L), respectively, both significantly lower (P < 0.001) than in controls, at
      5.1 (1.6) ng/L. On re-evaluation at T1, there was a significant (P < 0.001)
      increase in ADH levels over those at T0 in both groups, at 5.2 (0.8) and 5.3
      (1.9) ng/L, respectively. CONCLUSION: These results seem to confirm the role
      played by ADH in the pathophysiology of enuresis.

PMID- 9634022
TI  - Parents' and young people's attitudes towards bedwetting and their influence on
      behaviour, including readiness to engage in and persist with treatment.

PMID- 9634023
TI  - Sleep and night-time behaviour of enuretics and non-enuretics.
AB  - OBJECTIVE: To investigate connections between nocturnal enuresis and sleep
      factors such as the subjective depth of sleep and classical parasomnias.
      PATIENTS, SUBJECTS AND METHODS: One hundred school children aged 6-10 years
      answered a questionnaire, with their parents, and the same questions were asked
      of a group of 29 children of the same age suffering from severe nocturnal
      enuresis. RESULTS: There were significant differences in arousability, with the
      enuretic group being 'deep sleepers', and in the prevalence of onset insomnia,
      nightmares, interrupted sleep and bedtime struggles, which were all less common
      among the enuretics. The prevalence of classical parasomnias did not differ
      between the groups. CONCLUSION: A high arousal threshold is one of the
      pathogenetic factors underlying nocturnal enuresis and we propose that this group
      of therapy-resistant enuretic children might not only sleep more deeply than
      their nonenuretic peers, but perhaps have 'better' sleep.

PMID- 9634024
TI  - Changes in the structure of sleep spindles and delta waves on
      electroencephalography in patients with nocturnal enuresis.
AB  - OBJECTIVE: To evaluate the mechanism of the dysfunction of arousal in patients
      with Type I and Type IIa enuresis. PATIENTS AND METHODS: The numbers of sleep
      spindles and delta waves were analysed during electroencephalography in 19
      patients with enuresis (17 male, two female, mean age 9.7 years, range 8-14).
      RESULTS: In four patients with Type I enuresis, who awoke spontaneously and
      remained dry as a result of urinary sensation, the numbers of sleep spindles and
      delta waves diminished gradually and finally disappeared just before the patients
      awoke completely. In the remaining nine patients with Type I enuresis, there was
      no decrease in the number of sleep spindles and delta waves, and enuresis
      occurred without the subjects awakening. In the six patients with Type IIa
      enuresis, there was no arousal reaction or generation of sleep spindles on
      urination while asleep. CONCLUSIONS: An immaturity in the function of the
      thalamus might be a cause of the arousal dysfunction in patients with Type I
      enuresis. In Type IIa enuresis, a possible abnormal or immature arousal mechanism
      in the pons or the lower tract may be responsible.

PMID- 9634025
TI  - Continuous real-time ambulatory urodynamic monitoring in infants and young
      children using infrared telemetry.
AB  - OBJECTIVE: To assess the feasibility of continuous real-time ambulatory bladder
      monitoring in infants and young children using a specially developed ambulatory
      urodynamic data logger with built-in infrared telemetric on-line facilities.
      PATIENTS AND METHODS: Twenty-nine infants and young children (mean age 3.9 years,
      range 7 weeks to 9.5 years) with various types of bladder dysfunction underwent
      urodynamic studies performed using an ambulatory urodynamic recorder with a
      specially developed integral transmitter that converts digital pressure signals
      to modulated infrared waves (935 nm). A receiver mounted on the ceiling of the
      room receives the signals emitted from the recorder. During the investigation,
      the infant can conduct normal activities, be totally mobile and be accompanied by
      the mother undisturbed in a private cubicle. The urodynamicist in the next room
      can observe all the patient's activities through a one-way mirror while
      continuous real-time on-line pressure signal displays are recorded and monitored
      using a computer, with event markers placed as necessary. For security, the data
      recorded during ambulatory investigation are stored in the internal memory of the
      ambulatory recorder. RESULTS: All 29 infants and young children completed the
      urodynamic studies using the new system; the results were satisfactory and
      reliable, with no data lost during ambulatory recording. The results obtained
      using infrared telemetry were not significantly different from conventional
      natural-filling urodynamic studies performed with a cabled on-line urodynamic
      recorder. CONCLUSION: The infrared telemetry system provides a reliable and
      effective way of performing continuous real-time ambulatory urodynamic monitoring
      in infants and young children. With the development of more powerful telemetric
      data transmission technologies, such a method could be extended in the near
      future to a truly ambulatory urodynamic recording with real-time on-line
      facilities, either at home or in the clinic, both for adults and for children.

PMID- 9634026
TI  - Detrusor hypocontractility in children with posterior urethral valves arises
      before puberty.
AB  - OBJECTIVES: To assess prepubertal boys with posterior urethral valves (PUV) using
      an analysis of pressure-flow studies to evaluate the voiding phase and thus
      determine if myogenic failure (hypocontractility) arises before puberty and if it
      can be detected early. PATIENTS AND METHODS: Eleven boys (8-13 years old) with
      PUV underwent urodynamics and the results were analysed using pressure-flow
      mathematical analysis (PFA) of the following variables of detrusor activity:
      contraction velocity (Vdet), detrusor contractile power expressed as power factor
      (WF) and Schafer's diagram, which differentiates a 'strong', 'normal' and 'weak'
      detrusor. Vdet and WF were compared with normal values previously determined in
      boys of similar age and considered 'low' if more than 2 SDs below the mean. The
      results of PFA were compared with standard pressure-flow studies and the three
      classical urodynamic patterns in boys with PUV, as determined by voiding
      symptoms. The subsequent PFA of seven of the 11 boys were also assessed as they
      had undergone previous urodynamics when < 8 years old. RESULTS: As assessed by
      the three patterns of dysfunction, two boys had bladder instability, two had low
      compliance and three had hypocontractility, with four boys being normal. From the
      PFA, the Vdet and WF were lower than normal, respectively, in seven and nine of
      the 11 boys; Schafer's nomogram showed a 'weak' detrusor in seven boys. The PFA
      suggested a pathology in four of five boys with symptoms and in three of six with
      no symptoms (two of the six showing a 'low' WF). Moreover, in older (11-13 years)
      boys, all five had a 'weak' detrusor, a 'low' WF and four a 'low' Vdet. Of the
      seven patients who underwent repeat PFA, three had a stable WF 3 years later, one
      (normal) worsened slightly and two were clearly worse, while one, who underwent
      late (at 3 years old) valve ablation, had an increased WF. CONCLUSIONS: The PFA
      showed hypocontractility in two-thirds of prepubertal boys with PUV, including
      asymptomatic patients. These findings confirm the hypothesis that bladder
      dysfunction in boys with PUV eventually causes detrusor myogenic failure and
      finally a postpubertal overdistended bladder.

PMID- 9634027
TI  - An Italian epidemiological multicentre study of nocturnal enuresis.
AB  - OBJECTIVE: To estimate the prevalence of enuresis in schoolchildren in Italy.
      SUBJECTS AND METHODS: The Italian Club of Nocturnal Enuresis promoted a
      prevalence study of nocturnal enuresis using a self-administered questionnaire in
      seven cities in Northern, Central and Southern Italy. The association between
      enuresis and potential risk factors, e.g. a family history of enuresis, stress,
      socio-economic status and abnormal diurnal voiding habits, was investigated. The
      perceived impact on the child and on the family was also evaluated. A random
      cluster sampling scheme was used to obtain a sample of primary and secondary
      schoolchildren from each city. One primary school and one secondary school for
      each socio-economic level was sampled in each city, giving a total of 42 schools
      surveyed; 9086 children were covered by the survey. In a cluster sampling method,
      the variance of prevalence is divided into two components, binomial and extra
      binomial variability. Both the DSM III and DSM IV definitions of enuresis were
      used because at present, there is no consensus on the diagnostic criteria.
      RESULTS: Completed questionnaires were received from 7012 children, an overall
      response rate of 77.2%. Those aged 6-14 years were analysed, restricting the
      sample to 6892 children. There were 250 enuretic children using the DSM III
      definition of enuresis and 112 using the DSM IV definition. The overall
      prevalence was 3.88% and showed a decreasing trend with increasing age.
      Bedwetting was more frequent in boys than in girls. The prevalence of enuresis
      was higher when the child was from a family of low socio-economic status despite
      the child's age group. The logistic analysis showed that familiality, stress,
      birthweight, age of attaining diurnal continence, soiling and, for girls,
      menstruation, were statistically significant variables and thus contributed to
      predicting the probability of bedwetting, confirming the findings of previous
      studies. There was a large difference in prevalence using the two DSM
      definitions; a high percentage of DSM III enuretic children had more than two wet
      nights per week. CONCLUSION: It is important that a consensus about the 'working
      definitions' of enuresis is reached to avoid bias in the recruitment step, to
      carry out comparable epidemiological studies and to obtain adequate therapeutic
      responses.

PMID- 9634028
TI  - The natural history of urinary symptoms during adolescence.
AB  - OBJECTIVE: To determine the prevalence and natural history of urinary symptoms
      and incontinence among healthy adolescent schoolchildren. SUBJECTS AND METHODS: A
      prospective longitudinal study using a confidential questionnaire administered to
      an original cohort of 1176 local schoolchildren at 11-12 years and again at 15-16
      years old. RESULTS: There was a decrease in the prevalence of urinary symptoms
      with age. Daywetting was reported by 12.5% of children aged 11-12 years and 3.0%
      of children aged 15-16 years. Nocturnal enuresis was reported by 4.7% of children
      at 11-12 years and 1.1% at 15-16 years. Some of the children reporting daywetting
      and nocturnal enuresis at 15-16 years old had not reported these symptoms at 11
      12 years old. CONCLUSION: Urinary symptoms become less prevalent with age, but
      are reported by a significant number of healthy schoolchildren.

PMID- 9634029
TI  - A follow-up of enuresis from childhood to adolescence.
AB  - OBJECTIVE: To determine the prevalence and treatment of enuresis in a national
      population-based follow-up study of children aged 8-14 years, to evaluate
      possible factors that enhance or hamper the attainment of continence and to
      examine the relationships between enuresis and psychiatric disturbance. SUBJECTS
      AND METHODS: An initial study was carried out in 1989 as part of the Finnish
      Child Psychiatric National Epidemiological Study. Three types of questionnaires
      were used; the Rutter Scale A for completion by parents, including a question
      about enuresis, the Rutter scale B for completion by teachers and the Children's
      Depression Inventory (CDI), completed by the children. Parents were also asked
      about demographic and family issues, teachers about school achievements and
      children about additional psychosomatic symptoms. In a follow-up in 1995, the
      target population comprised all previous enuretics and their controls, matched by
      age, gender, class and school, in the first phase of the study. Replies were
      received from 315 enuretic boys and 186 girls, with the corresponding values for
      controls being 310 and 183. The parents were asked about the adolescents' present
      enuresis and for permission for a treatment trial, if needed. The adolescents
      completed the CDI, and a questionnaire about enuresis, previous treatments and
      possible willingness for a treatment trial. They also reported basic somatic
      data, their life events and living habits. RESULTS: In the initial study, the
      enuretic children had higher total and subscores as reported by parents, teachers
      and themselves, except for emotional items reported by the teachers.
      Additionally, a significantly greater proportion of these children soiled, had
      sleeping difficulties and difficulties in falling asleep. Enuretic boys had more
      frequent nightly arousal and early morning waking, while the enuretic girls had
      more nightmares than non-enuretic girls. At 14 years old, the parents reported
      that 13 adolescents were enuretic; from the children's replies, nine boys and
      seven girls were enuretic. CONCLUSIONS: The prevalence of enuresis in those
      previously enuretic was surprisingly low, probably because of the efficient
      treatment methods, conditioning and medication. There were evident connections
      between childhood enuresis and mental well-being.

PMID- 9634030
TI  - Perceived stress of nocturnal enuresis in childhood.

PMID- 9634031
TI  - Behavioural problems in children with urge incontinence and voiding postponement:
      a comparison of a paediatric and child psychiatric sample.
AB  - OBJECTIVE; To analyse prospectively the incidence of behavioural disorders and
      the subjective views of children with urge incontinence (defined by detrusor
      instability, sudden urge symptoms and frequent micturitions) and voiding
      postponement (characterized by delayed micturition in typical situations and a
      low voiding frequency) according to an identical protocol in a paediatric and a
      child psychiatric unit. PATIENTS AND METHOD: Ninety-four consecutive or randomly
      selected children aged 5.0-10.9 years with either voiding postponement (52) or
      urge incontinence (42) were examined prospectively using an intelligence test
      (CFT1 or CFT20), the Child Behaviour Checklist (CBCL 4/18), the ICD-10 child
      psychiatric diagnoses and a structured interview. RESULTS: In the groups from
      both centres combined, those postponing voiding had a significantly higher
      incidence of externalizing behavioural symptoms (31% vs. 8%; P < 0.01) and total
      problems (37% vs. 13%; P < 0.05) in the clinical range (CBCL), and a higher rate
      of at least one ICD-10 child psychiatric diagnosis (54% vs. 29% P < 0.05) and of
      expansive disorders (31% vs. 5%; P < 0.01). The incidence of children with
      behavioural symptoms was lower in the paediatric centre, being exceptionally low
      among urge incontinent children (only 6%, CBCL). In contrast, from the children's
      subjective appraisal, there were no significant differences in concepts,
      explanations and implications of wetting; 79% of urge incontinent children and
      64% of those postponing voiding suffered emotionally from the adverse effects of
      wetting. Only a minority (3% vs. 6%) saw any advantages at all. CONCLUSION:
      Children with voiding postponement had a significantly higher incidence of
      behavioural problems, especially expansive/externalizing behaviour, 3-4 times
      higher than in the normal population. Children with urge incontinence had a
      significantly lower incidence of behavioural problems, mainly emotional/
      internalizing behaviour, that was only slightly higher (1-2 times) than that in
      the normal population. Because of selection, similar trends but lower incidences
      were found in the paediatric setting, with very few problems among urge
      incontinent children. In contrast, the children's subjective views did not
      differ; disadvantages associated with emotional suffering were reported by all
      children.

PMID- 9634032
TI  - The objective assessment of urinary incontinence in children.
AB  - OBJECTIVE: To assess urinary incontinence objectively in children. PATIENTS AND
      METHODS: Thirty-three children (mean age 8.2 years, range 5-12) were examined, of
      whom 23 suffered from incontinence and 10 did not. The first method of assessing
      incontinence was the 1-h pad-weighing test proposed by the International
      Continence Society in 1983 and the second was a test in which the pad was weighed
      between one urination and the next. At the end of the tests the volume of
      normally voided urine was measured and the total voided volume during the test
      calculated. The volume of urine lost during incontinence and the ratio
      [incontinence volume/(incontinence volume + voided volume)] were evaluated; the
      ratio was used because the bladder capacity in children differed with age.
      RESULTS: In both tests, no wetting occurred in any of the 10 patients not
      complaining of incontinence. In the 1-h pad-weighing test, no wetting occurred in
      14 of the 23 patients complaining of incontinence but did in the nine remaining
      patients, the loss being 1-30 g, and the incontinence ratio 0.5-14.8%. In the
      second test, no wetting occurred in 12 of the 23 patients complaining of
      incontinence but did so in the 11 remaining patients, with losses of 2-50 g and
      incontinence ratios of 1.5-80.6%. CONCLUSIONS: There was no significant
      difference between the tests in the incidence of incontinence. However, the
      second method seemed to be more closely related to the clinical symptoms than was
      the 1-h pad-weighing test and may be useful in the assessment of incontinence in
      children.

PMID- 9634033
TI  - Pelvic-floor therapy in girls with recurrent urinary tract infections and
      dysfunctional voiding.
AB  - OBJECTIVE: To analyse the treatment of girls with recurrent urinary tract
      infections (UTIs, at least two periods confirmed) and urodynamically confirmed
      dysfunctional voiding with pelvic-floor therapy. PATIENTS AND METHODS: Forty-two
      girls with recurrent UTIs were treated prospectively during a study period of 18
      months. Training consisted of an individually adapted voiding and drinking
      schedule, pelvic-floor relaxation biofeedback, instructions on toilet behaviour
      and biofeedback uroflowmetry; residual urine was estimated by ultrasonography.
      All the girls received prophylactic antibiotics during treatment and those girls
      with urodynamically proven detrusor instability (33) received anticholinergics.
      Therapy was considered successful when the girls remained free of infection with
      no further prophylactic antibiotics for at least 6 months. RESULTS: Four girls
      younger than 6 years all suffered nocturnal and diurnal incontinence and two had
      reflux. Treatment was effective for recurrent UTI in all and the reflux resolved
      in two. All four girls became dry during the day and one became dry at night. In
      the 38 girls older than 6 years, the treatment was successful for recurrent UTI
      in 24 from the out-patient and in all three from the clinical programme. Reflux,
      which was seen in six of these girls, resolved in five; one girl underwent
      bilateral reimplantation. Incontinence was treated in all 23 girls with
      incontinence problems before treatment (four of whom were initially dry). Twelve
      girls needed a wetting alarm to become dry during the night. In four girls the
      treatment was effective for recurrent UTI but the incontinence persisted; in
      seven the treatment was considered unsuccessful as they all had UTIs after
      treatment; all remained incontinent. Reflux persisted in all four girls in this
      group who had reflux before treatment. CONCLUSION: The training programme was
      effective in treating recurrent UTI in 35 of 42 girls (83%). The persistence of
      incontinence problems is a bad prognostic factor for the recurrence of UTI after
      the training programme. Pelvic-floor therapy seems a reasonable and meaningful
      component in the treatment of recurrent UTIs in which detrusor-sphincter
      dyssynergia plays a role.

PMID- 9634034
TI  - Bladder autoaugmentation in myelodysplastic children.
AB  - OBJECTIVE: To present the long-term results of bladder autoaugmentation in
      myelodysplastic children with low compliance neurogenic bladders who failed
      attempts at medical management, including clean intermittent catheterization
      (CIC) and pharmacological bladder relaxation. PATIENTS AND METHODS: Twenty-one
      patients with a neurogenic bladder after myelomeningocele operations (mean age
      9.5 years, range 3-16) underwent autoaugmentation; 12 children were paraplegic
      and hydrocephalic, and were treated by insertion of a ventriculoperitoneal valve.
      All patients had low-compliance neurogenic bladders confirmed urodynamically. Ten
      patients had vesico-ureteric reflux (VUR) and eight had dilated upper urinary
      tracts with no reflux. All patients had been treated pre-operatively using CIC
      and anticholinergic agents, with no success. RESULTS: Of 21 children treated
      surgically, 17 were assessed urodynamically and examined to determine the
      condition of the upper and lower urinary tract. The follow-up ranged from 3
      months to 8 years (mean 6 years). In 13 patients the bladder capacity increased
      by approximately 60 mL and in 14 the intravesical pressure decreased by
      approximately 65 cmH2O. Fourteen children were continent using CIC (from 3- to 4
      hourly); in the six patients with VUR the reflux resolved in two, decreased in
      two and remained unchanged in two. Of eight patients with dilated upper tracts
      but no reflux, seven improved. There was no improvement in bladder capacity in
      four patients and no reduction in intravesical pressure in three. Two patients
      underwent enterocystoplasty (one ileocystoplasty and one colocystoplasty) with
      good results. Two children needed anticholinergic agents after autoaugmentation.
      CONCLUSIONS: Autoaugmentation effectively reduces high intravesical pressure and
      provides a sufficient increase in bladder capacity with a concomitant improvement
      in urodynamic values. The present method allows the extent of the surgical
      procedure to be limited to the extraperitoneal space and thus maintains all of
      other options. Bladder autoaugmentation is a reasonable alternative to
      enterocystoplasty in selected patients.

PMID- 9634035
TI  - Colorectal dysfunction and faecal incontinence in children with spina bifida.
AB  - OBJECTIVES: To quantify colorectal neurogenic dysfunction in children with spina
      bifida and to evaluate the clinical efficacy of appropriate rehabilitation
      performed by the coloproctologist in the spina bifida team. PATIENTS AND METHODS:
      The bowel function of 73 patients with congenital (67) and acquired (six) spinal
      lesions (age 7-25 years) was evaluated by one physician. Evacuation habit was
      classified as full bowel control, mild and severe constipation or incontinence.
      Fifty-two children had mild or severe incontinence or constipation, 22 of whom
      were treated by the coloproctologist using biofeedback or conventional therapy;
      30 were not treated. The outcome was compared between the groups RESULTS: Bowel
      constipation remained stable in 90% and was complicated in 10% of the untreated
      patients, while it ameliorated in 59% of patients who received specialist
      treatment. CONCLUSION: Neurogenic bowel dysfunction needs specialist management
      to achieve better results, using the concept of controlled incontinence. There
      was no significant difference between conventional therapy and biofeedback
      methods.

PMID- 9634036
TI  - Using multimedia for patient information--a program about nocturnal enuresis.
AB  - OBJECTIVES: To identify the information needs of children with nocturnal
      enuresis, and to design, produce and evaluate an interactive computer program to
      provide this information. SUBJECTS AND METHODS: The program was developed over an
      18-month period using information provided by children, parents and
      professionals, and was evaluated in a hospital-based enuresis clinic in 65
      children. Usability and knowledge gained were also evaluated in 43 healthy
      children aged 8-10 years attending a local inner-city primary school. RESULTS: An
      interactive program about nocturnal enuresis was developed, which runs on a
      personal computer and uses sound, voice, cartoon drawings and animation in a
      modular design. Knowledge scores increased in clinic attendees and in
      schoolchildren after using the program (Wilcoxon matched pairs test, P < 0.001).
      This improvement was maintained when the program was re-tested 6-10 months later.
      CONCLUSION: This interactive computer program holds children's attention and
      increases their understanding of enuresis. Interactive multimedia may be useful
      to complement the information provided by health professionals. This method of
      communication may be particularly useful for children with a low level of
      literacy.

PMID- 9634037
TI  - The value of family screening for patients with cystine stone disease in northern
      Jordan.
AB  - OBJECTIVE: To assess the prevalence of cystinuria and cystine stone disease among
      families of patients with cystine stones, and to determine their distribution by
      age, sex and associated morbidity. SUBJECTS AND METHODS: The study comprised 180
      relatives (87 males and 93 females, mean age 43 years) descended from two
      brothers over four generations who live in two areas in northern Jordan. Data
      were collected using a questionnaire and home visits, by urinary cystine testing
      and radiology to detect stone, and assessing hypertension and renal impairment.
      RESULTS: Of the 180 subjects, 104 (58%) had a positive reaction for cystine in
      urine; 33 (32%) of these were younger than 15 years. Twenty members (11%) of the
      families had evidence of renal cystine stone disease. Hypertension and renal
      impairment were detected in a significant proportion of individuals with cystine
      stone disease. CONCLUSION: Cystinuria is a major risk factor for cystine stone
      formation. Family screening is valuable in detecting the cystinuric population
      and in assessing individuals with stones. Early recognition, treatment and
      counselling result in better management and prevention. The establishment of a
      cystine study group in our region is essential.

PMID- 9634038
TI  - Gene expression of prothrombin in the human kidney and its potential relevance to
      kidney stone disease.
AB  - OBJECTIVE: To determine whether urinary prothrombin fragment 1 (UPTF1), which
      shows considerable promise as a critical determinant of calcium oxalate (CaOx)
      stone formation, is manufactured by the human kidney. MATERIALS AND METHODS:
      Ribonucleic acid was isolated from eight kidneys, two spleens and one liver.
      Using reverse transcriptase-polymerase chain reaction, mRNA corresponding to the
      UPTF1 portion of prothrombin was analysed by agarose-gel electrophoresis and
      Southern blotting. RESULTS: Six kidney specimens showed clear evidence of
      prothrombin gene expression; expression in the kidney was less than that in the
      liver. CONCLUSION: This is the first demonstration of prothrombin gene expression
      within the human kidney, a finding that not only has implications for CaOx stone
      disease but also potentially for blood coagulation.

PMID- 9634039
TI  - Nephroplication and nephropexy as an adjunct to primary surgery in the management
      of giant hydronephrosis.
AB  - OBJECTIVE: To study the role of nephroplication and nephropexy as an adjunct to
      primary surgery in the management of giant hydronephrosis, with an aim to reduce
      stasis and improve drainage, thus preventing consequent complications. PATIENTS
      AND METHODS: Adjunctive nephroplication and nephropexy were performed in 20 renal
      units of 16 patients with giant hydronephrosis treated between January 1992 and
      March 1997. Twelve patients had unilateral and four had bilateral pelvi-ureteric
      junction obstruction. Four patients had elevated serum creatinine levels. All
      patients were treated with definitive surgery for the underlying disease and an
      adjunctive nephroplication and nephropexy was performed at the same time.
      RESULTS: Eighteen of the 20 renal units with giant hydronephrosis showed an
      improvement in function and drainage as well as in pelvicalyceal system
      dilatation, while one remained unchanged and one deteriorated. None of the
      patients developed renal stones or pyelonephritis. Of the four patients with
      azotaemia, three showed definite improvement to normal levels while one
      stabilized. CONCLUSIONS: Nephroplication and nephropexy of giant hydronephrotic
      kidneys are useful adjunctive procedures to reduce pelvicalyceal system stasis
      and to improve drainage, thereby preventing subsequent stone formation, infection
      and deterioration in renal function.

PMID- 9634040
TI  - Rigid ureteroscopy in pregnant women.
AB  - OBJECTIVE: To report our experience with rigid ureteroscopy in pregnant women.
      PATIENTS AND METHODS: Ten pregnant women (mean age 25 years, SD 4.5, range 22-33)
      with ureteric stones were treated by ureteroscopy. The mean (SD, range) gestation
      time was 24 (6.5, 19-33) weeks. A standard rigid ureteroscope of 11.5 F was used
      in eight patients and 9.5 F in two. The procedure was carried out with no
      ureteric dilatation in three patients and with easy dilatation in seven.
      Fluoroscopy was not used before or during ureteroscopy in any case.
      Ultrasonography was available throughout the procedures for constant renal and
      obstetric monitoring. RESULTS: Mid and lower ureteric stones were extracted by
      basket or forceps in three patients and had to be disintegrated by ultrasound in
      two. Upper ureteric stones were displaced to the kidney, with placement of double
      pigtail ureteric stents, in three patients who were subsequently treated after
      delivery. Ureteric oedema was seen in one patient and the endoscopic findings
      were normal in the remaining patient. There were no obstetric complications. Two
      patients had a urinary tract infection and one complained of stent-induced
      bladder irritation. CONCLUSIONS: Rigid ureteroscopy is a safe and reliable method
      in the diagnosis and treatment of ureteric calculi during pregnancy. The
      procedure can be performed with ultrasonographic monitoring and without using
      fluoroscopy.

PMID- 9634041
TI  - The relevance of parity to ureteric dilatation.
AB  - OBJECTIVE: To assess whether the mild dilatation of the right ureter in women
      that is sometimes seen on intravenous urography (IVU) represents persistent
      dilatation after a previous pregnancy. PATIENTS AND METHODS: The intravenous
      urograms of 71 men, 63 parous and 27 nulliparous women were evaluated
      prospectively. The two groups of women were divided into those with and without a
      confirmed history of urinary tract infection (UTI) as the indication for IVU.
      producing five groups in all. Measurements were taken on both the 5-min and the
      compressed or release films on each side. RESULTS: There were no significant
      differences in ureteric diameters among the five groups for the uncompressed
      right ureter (P=0.23), the left ureter uncompressed (P=0.32) or compressed
      (P=0.87). For the compressed right ureter, the difference was significant, with
      the diameters in the parous women with proven UTIs being larger than in the other
      groups (P=0.043). CONCLUSION: There is a significant increase in the diameter of
      the compressed right ureter in the group of parous women with a history of proven
      UTI. Infection or parity alone do not produce this effect: the combination of the
      two factors is required.

PMID- 9634042
TI  - Evaluation of clinical staging before cystectomy in transitional cell bladder
      carcinoma: a long-term follow-up of 276 consecutive patients.
AB  - OBJECTIVE: To evaluate retrospectively the clinical staging in a consecutive
      series of patients selected for cystectomy and to define its limitations with a
      view to possible improvements. PATIENTS AND METHODS: From 1979 to 1988, 276
      patients with newly detected or recurring transitional cell carcinoma (TCC) of
      the bladder, were offered pre-operative irradiation (20 Gy) and cystectomy. The
      patients were assessed during 1995 and the outcome related to both clinical and
      surgical data. Survival was analysed on the basis of 'intention to treat'.
      Estimates of survival probabilities were calculated by the method of Kaplan and
      Meier. Differences in survival among subgroups were assessed using the log rank
      test and Cox stepwise regression analysis. RESULTS: Cancer-specific actuarial
      survival for the whole series was 68% at 5 years and 63% at 10 years. Survival
      was closely related to the depth of invasion found at surgery, clearly
      discriminating those with tumours confined to the bladder wall (< or = P3A) from
      those with extravesical extension (> or = P3B). The cancer-specific survival at 5
      years for patients with < or = P3A tumours was 85% and for those with > or = P3B
      tumours was 50%. This important distinction was anticipated accurately using
      bimanual palpation before surgery, those patients with no palpable mass after
      transurethral resection of bladder tumour (TURBT) having an actuarial survival of
      83%, and those with a residual mass a survival of 50% at 5 years. In the
      multivariate analysis, increasing clinical stage was the only pretreatment
      variable with significant prognostic value for survival. However, this variable
      was highly dependent on the palpatory findings after TURBT, the presence of a
      residual mass being a prerequisite for the clinical stage T3 in case of muscle
      invasive tumour. CONCLUSION: Bimanual palpation remains crucially important in
      clinical staging, and there is a need for further standardization and refinement
      of this procedure.

PMID- 9634043
TI  - The early clinical course of primary Ta and T1 bladder cancer: a proposed
      prognostic index.
AB  - OBJECTIVE: To develop a simple prognostic index for anticipating more precisely
      the early clinical course of primary superficial bladder cancer. PATIENTS AND
      METHODS: The prognostic value of patient and tumour characteristics was examined
      in 333 patients with primary Ta or T1 bladder cancer who participated in a
      multicentre prospective study already completed. Primary tumour multiplicity, a
      diameter of > 3 cm, stage T1, and grade 2 or 3 were independent predictors of
      earlier recurrence in a multivariate analysis. A simplified prognostic index
      consisted of the number of adverse tumour characteristics (ATCs) initially
      present. RESULTS: After a median follow-up of 35.3 months, the 60 patients free
      of ATCs (19%) had a recurrence-free probability at 12 and 24 months of 86% and
      69%, respectively, and none experienced progression. Recurrence outcomes
      deteriorated consistently as the number of ATCs increased among the other three
      groups. In patients with 3-4 ATCs, the 12- and 24-month recurrence-free
      probability was as low as 30% and 19%, and recurrence and tumour rates were about
      2.6 times higher than in patients free of ATCs; 7% of these patients experienced
      progression within 35 months of follow-up. CONCLUSION: A prognostic index based
      on the number of ATCs (primary tumour multiplicity, diameter > 3 cm, stage T1,
      and grade 2 or 3) is a strong indicator of the clinical course of superficial
      bladder cancer within 3 years of the first endoscopic resection. This proposal is
      suggested for discussion and for validation in future studies but if confirmed,
      this simple prognostic index may greatly help to identify indicators for adjuvant
      intravesical therapy and to determine the optimal periodicity of control
      cystoscopy regimens.

PMID- 9634044
TI  - An evaluation of quality of life in patients with continent urinary diversions
      after cystectomy.
AB  - OBJECTIVE: To determine the long-term results and assess the quality of life in
      patients with continent urinary diversions after cystectomy. PATIENTS AND
      METHODS: Eighty-six consecutive patients who received a continent urinary
      diversion from 1988 to 1994 at the Vancouver Hospital and Health Sciences Center
      were evaluated. The evaluation comprised a review of their hospital charts and
      clinic visits at 3 months and then yearly. Quality of life issues were assessed
      using a postal questionnaire pertaining to the patient's urinary symptoms.
      activity level and overall well-being while living with a continent urinary
      diversion. Two separate questionnaires were sent, addressing heterotopic or
      orthotopic diversions. RESULTS: There was an acceptable rate of complications,
      with stone formation and urinary tract infection as the most common morbidities.
      Continence was rated as good in most patients, with no patient reporting complete
      incontinence. Undesirable urinary symptoms occurred less often than 20% of the
      time in most patients. Although there was a significant effect on sex life, the
      overall quality of life appeared to be very good, as 70% of the patients had no
      limitations to their activities. CONCLUSIONS: The techniques currently evolved
      for urinary diversion produce good long-term results and quality of life. These
      diversions should be considered in a well selected patient population.

PMID- 9634045
TI  - The impact of a modified ileal neobladder on the lifestyle and voiding patterns
      in Asian patients.
AB  - OBJECTIVE: To evaluate the impact of the modified ileal neobladder reconstruction
      on lifestyle, voiding habits and functional outcome in Asian patients. PATIENTS
      AND METHODS: Twenty-seven Asian patients (25 men and two women, mean age 59
      years, range 41-76) underwent modified ileal neobladder reconstruction after
      radical cystectomy for carcinoma of the bladder. The mean (range) follow-up was
      21 (3-75) months. All patients were evaluated retrospectively using case notes,
      reviews, interviews and voiding charts; 18 patients underwent urodynamic studies.
      RESULT: Twenty-five patients (93%) achieved diurnal and 23 (85%) nocturnal
      continence within 6 months. Of the 19 patients who were in employment before
      surgery, 15 continued to be economically active afterward; 26 patients (96%)
      reported no change in their daily living activities. Of 16 men who reported being
      potent pre-operatively only four retained some residual erectile function. Twenty
      three patients were interviewed about their voiding habits and satisfaction with
      the outcome of surgery. Fourteen patients had no sensation of reservoir fullness
      and of the 21 men, 13 had to squat or sit to void effectively. The mean (range)
      voiding frequency was 5 (4-8) during the day and 2 (0-4) during sleep. Twenty-two
      patients were satisfied with the overall outcome. CONCLUSIONS: The modified ileal
      bladder provides a high urinary continence rate with minimal changes in daily
      living activities and occupational status. The functional outcome was very
      satisfactory and accepted well, despite some changes in reservoir sensation,
      voiding posture and erectile function. The method is a viable option for
      reconstruction after cystectomy in Asian patients.

PMID- 9634046
TI  - The accuracy of the frequency-volume chart: comparison of self-reported and
      measured volumes.
AB  - OBJECTIVE: To assess the accuracy of frequency-volume charts recorded by patients
      with voiding symptoms by comparing self-reported voiding data with the volumes of
      urine collected in same period. PATIENTS AND METHODS: The study comprised 18
      patients (median age 63 years, range 20-80) and lasted 3 days, during which the
      patients recorded their fluid intake and voided volumes, and collected 24 h urine
      samples. RESULTS: The recorded volumes exceeded or underestimated the collected
      volume in 49% and 51%, respectively, of the samples, but the agreement between
      the accumulated daily voiding volumes on the charts and the volumes collected was
      acceptable. The median difference between volumes recorded on the charts and
      collected as samples was 100 (0-1450) mL per 24 h or 10 (0-117) mL per voiding
      (not significant). The median daily variation of creatinine in the urine was 1.1
      (0.1-9.4) mmol (not significant), indicating that the 24 h collection periods
      were respected. CONCLUSION: Recordings on frequency-volume charts are valid and
      useful in the investigation of patients with voiding symptoms.

PMID- 9634047
TI  - The management of men with acute urinary retention. National Prostatectomy Audit
      Steering Group.
AB  - OBJECTIVES: To determine the outcome of men with acute urinary retention
      undergoing prostatectomy and to assess whether discharge with a catheter before
      subsequent planned re-admission for prostatectomy had an adverse effect on
      outcome. PATIENTS AND METHODS: A prospective cohort study was conducted of all
      men undergoing prostatectomy in five health care regions over a 6-month period in
      56 hospitals where prostatectomies were performed under the care of 103 surgeons.
      The study included 3966 men undergoing prostatectomy, of whom 1242 presented with
      acute urinary retention; the complication rates and symptomatic outcome were
      assessed. RESULTS: Compared with those who underwent elective prostatectomy for
      symptoms alone, men presenting with acute retention had an excess risk of death
      at 30 days (relative risk [RR], 26.6, 95% confidence interval [CI], 3.5-204.5)
      and at 90 days after operation (RR 4.4, 95% CI 2.5-7.6), and an increased risk of
      perioperative complications. Although men with retention were older, had larger
      glands and had more comorbidity, these factors did not totally explain the excess
      risk. The final symptomatic outcome of men with acute retention was no different
      from that of men presenting for elective treatment. Men with retention who were
      managed by initial catheterization, sent home and subsequently re-admitted for
      planned operation had similar pretreatment characteristics, post-operative
      complications and outcomes to those who were kept in hospital throughout,
      although the men kept in hospital had a total increased length of stay.
      CONCLUSIONS: Men with acute retention have a high risk of developing
      complications after undergoing prostatectomy. We were unable to confirm that a
      short-term period of catheter drainage at home before re-admission for planned
      surgery carried increased risks of peri-operative complications.

PMID- 9634048
TI  - Transurethral electrovaporization of the prostate--a possible alternative to
      transurethral resection: a one-year follow-up of a prospective randomized trial.
AB  - OBJECTIVE: To compare the efficacy, safety and durability of transurethral
      electrovaporization of the prostate (TUVP) with standard transurethral resection
      (TURP) in a prospective randomized trial. PATIENTS AND METHODS: The study
      included 104 consecutive men with symptomatic benign prostatic hyperplasia (BPH)
      admitted for surgery who were randomized to TUVP or TURP. The variables evaluated
      included the duration of surgery, catheterization and hospital stay, the
      International Prostate Symptom Score (IPSS), a quality-of-life assessment (QOL),
      the maximum urinary flow rate (Qmax) and the postvoid residual urine volume
      (PVR). RESULTS: Both groups showed a comparable significant and maintained
      decline in the mean IPSS, from 26.5 to 4.4 (TUVP) and from 26.6 to 5.9 (TURP),
      and increase in mean Qmax, from 8.6 to 20.8 mL/s [corrected] (TUVP) and 8.6 to
      22.8 mL/s (TURP) after 1 year. However, there were significant differences in the
      mean duration of catheterization (TUVP 20.9 h, TURP 46.6 h, P<0.001), hospital
      stay (TUVP 2.2 day, TURP 3.1 days, P<0.001), and the duration and volume of post
      operative irrigation (TUVP none, TURP 18.1 h with 17.5 L of saline). Two patients
      in each group developed urethral strictures (4%) and two patients in each group
      required re-operation for residual adenoma (4%); two patients undergoing TURP had
      a bladder neck stricture (4%). CONCLUSION: The results suggest that TUVP is as
      effective as standard TURP in the treatment of moderate-sized BPH. TUVP offers
      the advantage of using established instruments, has excellent peri-operative
      haemostasis and requires a shorter hospital stay.

PMID- 9634049
TI  - Interstitial radiofrequency therapy of the prostate in the management of acute
      urinary retention.
AB  - OBJECTIVE: To evaluate in a prospective study the efficacy of interstitial
      radiofrequency therapy (IRFT) of the prostate in relieving acute urinary
      retention in patients with benign prostatic hyperplasia. PATIENTS AND METHODS:
      Twenty-seven patients presenting in acute urinary retention who failed at least
      one trial of voiding one week after presentation were treated with IRFT of the
      prostate. During the 6-month follow-up, the International Prostate Symptom Score
      (IPSS), urinary flow rate, post-void residual volume (PVR) and serum creatinine
      were determined and changes in erectile and ejaculatory functions recorded. The
      treatment was considered successful if the patient resumed normal voiding,
      without compromising renal function and without troublesome lower urinary tract
      symptoms necessitating further treatment. RESULTS: Of the 26 evaluable patients,
      77% resumed normal voiding. At 6 months after treatment, the mean (SD) IPSS had
      decreased from 15.0 (8.3) to 8 (5.4), the PVR from 950 (203) to 88 (60) mL and
      the maximum flow rate was 10.5 (4.36) mL/s. CONCLUSION: IRFT of the prostate is a
      safe and effective treatment, at least in the short-term, for relieving acute
      urinary retention in patients with benign prostatic hyperplasia. The longer term
      follow-up is continuing.

PMID- 9634050
TI  - Decreased incidence of prostate cancer with selenium supplementation: results of
      a double-blind cancer prevention trial.
AB  - OBJECTIVE: To test if supplemental dietary selenium is associated with changes in
      the incidence of prostate cancer. PATIENTS AND METHOD: A total of 974 men with a
      history of either a basal cell or squamous cell carcinoma were randomized to
      either a daily supplement of 200 microg of selenium or a placebo. Patients were
      treated for a mean of 4.5 years and followed for a mean of 6.5 years. RESULTS:
      Selenium treatment was associated with a significant (63%) reduction in the
      secondary endpoint of prostate cancer incidence during 1983-93. There were 13
      prostate cancer cases in the selenium-treated group and 35 cases in the placebo
      group (relative risk, RR=0.37, P=0.002). Restricting the analysis to the 843
      patients with initially normal levels of prostate-specific antigen (< or = 4
      ng/mL), only four cases were diagnosed in the selenium-treated group and 16 cases
      were diagnosed in the placebo group after a 2 year treatment lag, (RR=0.26
      P=0.009). There were significant health benefits also for the other secondary
      endpoints of total cancer mortality, and the incidence of total, lung and
      colorectal cancer. There was no significant change in incidence for the primary
      endpoints of basal and squamous cell carcinoma of the skin. In light of these
      results, the 'blinded' phase of this trial was stopped early. CONCLUSIONS:
      Although selenium shows no protective effects against the primary endpoint of
      squamous and basal cell carcinomas of the skin, the selenium-treated group had
      substantial reductions in the incidence of prostate cancer, and total cancer
      incidence and mortality that demand further evaluation in well-controlled
      prevention trials.

PMID- 9634051
TI  - Urethroplasty for balanitis xerotica obliterans.
AB  - OBJECTIVE: To review the results of different methods of urethroplasty for
      anterior urethral strictures caused by balanitis xerotica obliterans (BXO).
      PATIENTS AND METHODS: Twenty-eight patients underwent urethroplasty for BXO; 12
      had a one-stage pedicled penile skin-flap urethroplasty and 16 excision and a two
      stage free-graft urethroplasty using nongenital skin. RESULTS: The treatment
      failed in all patients undergoing a one-stage pedicle penile skin urethroplasty
      because the disease recurred with BXO, whereas the treatment failed in only one
      patient using a two-stage free graft procedure. CONCLUSION: A two-stage free
      graft urethroplasty using nongenital skin is recommended for anterior urethral
      strictures caused by BXO.

PMID- 9634052
TI  - Early experience with the use of buccal mucosa for substitution urethroplasty.
AB  - OBJECTIVE: To evaluate the early results of anterior urethroplasty using a one
      stage free graft with buccal mucosa. PATIENTS AND METHOD: Thirty-nine patients
      (aged 23-59 years) underwent a one-stage urethroplasty using buccal mucosa, 28 as
      a patch and 11 as tube grafts. All patients were evaluated by post-operative
      urethrography at 6 months and were followed using urinary flow rates and symptoms
      for 2-5 years. RESULT: There was one recurrent stricture (3%) in the group with a
      patch urethroplasty but five of the 11 patients with tube grafts had a recurrent
      stricture. CONCLUSION: The early results using buccal mucosa for patch
      urethroplasty are encouraging. Although the results from tube grafts are poor,
      they are similar to those from other methods of single-stage urethroplasty.

PMID- 9634053
TI  - Managing many patients with a urethral stricture: a cost-benefit analysis of
      treatment options.
AB  - OBJECTIVES: To report a management method in a community where there are many
      patients with urethral stricture and where the short-term goal of providing some
      treatment to most may override the sometimes conflicting long-term aim of
      minimizing recurrence rates. PATIENTS AND METHODS: Over a 3-year period, using
      optical urethrotomy in 76 patients followed by intermittent self-dilatation (ISD)
      in 29, urethroplasty in 28 and dilatation in three, 92 of 134 patients with a
      urethral stricture were treated and the outcome compared. RESULTS: The overall
      recurrence rate was 22%; a combination of urethrotomy plus ISD had a recurrence
      rate of 17% and gave a mean duration of follow-up without recurrence similar to
      that after urethroplasty. ISD significantly increased both the time before
      recurrence and the duration of follow-up without recurrence after urethrotomy. In
      addition to providing lasting treatment to many patients, urethrotomy was also 10
      times cheaper, 10 times faster to perform and offered the surgeon better
      protection from infection with human immunodeficiency virus than did
      urethroplasty. CONCLUSION: Because wrongly selecting urethrotomy (resulting in a
      failed procedure) wastes valuable operating time and resources, the pre-operative
      recognition of strictures unsuitable for urethrotomy and their treatment by
      urethroplasty is important for overall efficiency.

PMID- 9634054
TI  - Histological changes associated with long-term urethral stents.
AB  - OBJECTIVE: To assess the histological changes found in patients with long-term
      external sphincter, prostatic and urethral stents. PATIENTS AND METHODS: Eighteen
      patients with long-term stents (mean time since insertion 3.5 years) were
      investigated. Three had external sphincter stents for detrusor-sphincter
      dyssynergia secondary to spinal injury, eight had prostatic stents for
      obstruction secondary to benign prostatic hyperplasia and seven had urethral
      stents for recurrent strictures. Nine stents were occluded at investigation, of
      which seven were entirely removed. The mucosae overlying the remaining two were
      biopsied, as were mucosae over the nine patent stents, at urethroscopy. RESULTS:
      The changes observed included polypoid hyperplasia (11 of 18 patients) between
      and around the stent mesh wires, nonkeratinizing squamous metaplasia (two) or
      hyperkeratotic squamous metaplasia (seven), chronic inflammation (15) with
      prominent plasma cell infiltrates (11), variable foreign-body granuloma (two) and
      microabscess formation (five), usually associated with clefts formed around the
      stent wires (three of five). CONCLUSION: Stents become incorporated into the
      urethral wall by a process of polypoid hyperplasia through the stent mesh, with
      at least focal covering of the stent in most cases, and with variable
      inflammatory infiltrates, most of which are rich in plasma cells. The urothelial
      and connective tissue proliferation resulted in obstruction of the stent lumen in
      nine of the patients studied. Further long-term study is necessary to exclude the
      development of carcinoma in patients with keratinizing squamous metaplasia,
      although no malignancy was seen in this study.

PMID- 9634055
TI  - The outcome of varicocelectomy in subfertile men with an absent or atrophic right
      testis.
AB  - OBJECTIVES: To determine the effects of varicocelectomy on semen quality,
      testicular volumes and serum hormone levels in subfertile men with an absent or
      atrophic right testis. PATIENTS AND METHODS: Seventeen patients whose wives were
      gynaecologically normal were evaluated with at least two semen analyses and
      measurements of serum hormone levels and antisperm antibodies. Scrotal
      ultrasonography was used to determine testicular volumes and spermatic vein
      diameters. Varicocelectomy was performed by high ligation via an inguinal
      approach. All patients were seen at a follow-up 3 months later, and after 6, 9
      and 12 months the scrotal ultrasonography, hormone assessment and semen analyses
      were repeated. Any pregnancies in their wives were recorded over a median follow
      up of 19 months. RESULTS: After surgery, all patients had significant
      improvements in sperm motility, morphology and concentration (P<0.01) but the
      differences in pre- and post-operative testicular volumes and plasma hormone
      levels were not statistically significant (P>0.01). No patients had immunological
      infertility. Eleven of the wives became pregnant during the follow-up.
      CONCLUSION: Higher pregnancy rates can be achieved by left varicocelectomy in
      subfertile men with an absent or atrophic right testis. Sperm concentration,
      motility and morphology are significantly improved by varicocelectomy.

PMID- 9634056
TI  - Epididymectomy in the management of intrascrotal disease: a critical reappraisal.
AB  - OBJECTIVE: To assess the outcome of epididymectomy as a method of treating
      epididymal pathology. PATIENTS AND METHODS: Forty-one patients who underwent
      epididymectomy between 1990 and 1995 were analysed retrospectively; their
      clinical records were reviewed and their satisfaction with the outcome and relief
      of symptoms assessed using a questionnaire and/or telephone interview. RESULTS:
      Twenty-nine patients with pain were subdivided into three categories depending on
      the indication for epididymectomy, i.e. post-vasectomy epididymal engorgement
      (eight patients), complex cystic disease (11) or 'chronic epididymitis' (10). The
      outcome was satisfactory in 27 of the 29 patients. The best results were obtained
      in the group who underwent epididymectomy after vasectomy, where seven of eight
      improved after the procedure. Those with chronic epididymitis had the least
      favourable outcome, with only seven reporting any improvement in symptoms.
      CONCLUSIONS: Epididymectomy has a valuable role in the management of epididymal
      pathology in appropriately selected patients.

PMID- 9634057
TI  - Endoscopic removal of a complex foreign body from the bladder.

PMID- 9634058
TI  - Ureteroscopic retrieval of proximally displaced ureteric stents using triradiate
      grasping forceps.

PMID- 9634059
TI  - Benign teratoma of the urachus.

PMID- 9634060
TI  - Exstrophic abdominal wall defect without bladder exstrophy (pseudo-exstrophy)

PMID- 9634061
TI  - Urinary bladder rupture: laparoscopic repair.

PMID- 9634062
TI  - Urinary incontinence: an unusual manifestation of a forgotten stent.

PMID- 9634063
TI  - Retroperitoneal fibrosis: an unusual complication of intra-arterial stents and
      angioplasty.

PMID- 9634064
TI  - 'Stones, gas and gaiters': gas-filled matrix calculi of the renal pelvis.

PMID- 9634065
TI  - Renal angiomyolipoma associated with inferior vena caval tumour thrombus.

PMID- 9634066
TI  - A peculiar case of granulomatous prostatitis: a cause for concern.

PMID- 9634067
TI  - Metastatic prostatic carcinoma in a male-to-female transsexual.

PMID- 9634068
TI  - Spontaneous anticoagulant-induced testicular haemorrhage mimicking a testicular
      tumour.

PMID- 9634069
TI  - Safety and efficacy of transurethral needle ablation of the prostate for
      symptomatic outlet obstruction.

PMID- 9634070
TI  - Clinical review of 100 consecutive surgically treated patients with upper tract
      transitional tumours.

PMID- 9634071
TI  - The use of the bladder-tumour associated analyte test to determine the type of
      cystoscopy in the follow-up of patients with bladder cancer.

PMID- 9634072
TI  - Viral proteins that regulate cellular signalling.

PMID- 9634073
TI  - Retrovirus mutation rates and their role in genetic variation.

PMID- 9634074
TI  - A proline-to-histidine substitution at position 225 of human immunodeficiency
      virus type 1 (HIV-1) reverse transcriptase (RT) sensitizes HIV-1 RT to BHAP U
      90152.
AB  - Two mutant virus strains in which the novel P225H mutation appeared in a V106A
      reverse transcriptase (RT)-mutated genetic background upon treatment of human
      immunodeficiency virus type 1 (HIV-1) with quinoxaline S-2720 were isolated.
      Surprisingly, the addition of the P225H mutation to the V106A RT mutant genetic
      background resensitized the V106A RT mutant virus to the non-nucleoside RT
      inhibitor (NNRTI) BHAP U-90152, but not to other NNRTIs. Construction of both
      recombinant viruses and recombinant RTs containing the V106A, P225H and
      V106A+P225H mutations revealed that P225H was indeed responsible for the marked
      potentiation of the antiviral activity of BHAP against the P225H single-mutant
      virus and the V106A+P225H double-mutant virus when compared to wild-type and
      V106A single-mutant viruses, respectively. An explanation for the markedly
      increased sensitivity of the P225H mutant HIV-1 RT to BHAP and not to the other
      NNRTIs was provided by the unique features of the X-ray structure of the RT-BHAP
      complex.

PMID- 9634075
TI  - Mycobacterium tuberculosis mannose-capped lipoarabinomannan can induce NF-kappaB
      dependent activation of human immunodeficiency virus type 1 long terminal repeat
      in T cells.
AB  - Tuberculosis has emerged as an epidemic, extended by the large number of
      individuals infected with human immunodeficiency virus type 1 (HIV-1). The major
      goal of this study was to determine whether the mycobacterial cell wall component
      mannose-capped lipoarabinomannan (ManLAM) of Mycobacterium tuberculosis (M.
      tuberculosis) could activate transcription of HIV-1 in T cells with the use of an
      in vitro cell culture system. These experiments are of prime importance
      considering that CD4-expressing T lymphocytes represent the major virus reservoir
      in the peripheral blood of infected individuals. Using the 1G5 cell line
      harbouring the luciferase reporter gene under the control of the HIV-1 LTR, it
      was first found that culture protein filtrates (CFP) from M. tuberculosis or
      purified ManLAM could activate HIV-1 LTR-dependent gene expression unlike
      similarly prepared CFP extracts devoid of ManLAM. The implication of protein
      tyrosine kinase(s), protein kinase A and/or protein kinase C was highlighted by
      the abrogation of the ManLAM-mediated activation of HIV-1 LTR-driven gene
      expression using herbimycin A and H7. It was also determined, using
      electrophoresis mobility shift assays, that M. tuberculosis ManLAM led to the
      nuclear translocation of the transcription factor NF-kappaB. M. tuberculosis
      ManLAM resulted in clear induction of the luciferase gene placed under the
      control of the wild-type, but not the kappaB-mutated, HIV-1 LTR region. Finally,
      the ManLAM-mediated activation of HIV-1 LTR transcription was found to be
      independent of the autocrine or paracrine action of endogenous TNF-alpha. The
      results suggest that M. tuberculosis can upregulate HIV-1 expression in T cells
      and could thus have the potential to influence the pathogenesis of HIV-1
      infection.

PMID- 9634076
TI  - Dependence on host cell cycle for activation of human immunodeficiency virus type
      1 gene expression from latency.
AB  - Human immunodeficiency virus type 1 (HIV-1) establishes latent infection of a
      certain population of CD4+ host cells which could be long-term reservoirs for HIV
      1. The expression of viral genes in such long-term infected cells is strongly
      regulated by cellular status, such as the phase of the cell cycle or stage of
      cell differentiation. Here, viral gene expression in synchronized U1 cells, a
      monocytic cell clone latently infected with HIV-1, was characterized. The
      expression of HIV-1 antigens was detected exclusively at G2/M phase in U1 cells,
      irrespective of phorbol myristate acetate (PMA) treatment. The induction of HIV-1
      gene expression in PMA-treated cells was due to the recruitment of NF-kappaB with
      DNA-binding activity at G2/M phase. Activated NF-kappaB was induced only by PMA
      treatment during the late G1 to S, but not after entering G2 phase, indicating
      that the transcriptional factor(s) involved in viral gene expression is also
      largely regulated by the host cell cycle. In contrast, the enhancement of antigen
      expression by treatment with tumour necrosis factor-alpha (TNF-alpha) was cell
      cycle-independent. In fact, NF-kappaB was activated 2 h after TNF-alpha treatment
      at all stages of the cell cycle. Thus, the mechanisms of HIV-1 activation from
      latency in U1 cells by PMA and TNF-alpha treatment are different. The model
      system using U1 cells shown here may provide insight into the mechanisms
      responsible for HIV-1 gene expression from latency.

PMID- 9634077
TI  - Sequence analysis of the NS5A protein of European hepatitis C virus 1b isolates
      and relation to interferon sensitivity.
AB  - Japanese studies have defined the discrete 2209-2248 amino acid region of the non
      structural 5A protein (NS5A(2209-2248)) of hepatitis C virus genotype 1b (HCV 1b)
      isolates as the interferon sensitivity determining region (ISDR). European
      studies did not confirm these results since most of the ISDR sequences harboured
      an intermediate profile. Recently, a direct interaction between the NS5A protein,
      involving the ISDR, and the interferon-induced protein kinase (PKR) has been
      reported and presented as a possible explanation of HCV interferon resistance. In
      the present study, the entire NS5A amino acid sequence from 11 resistant and
      eight sensitive strains from European HCV 1b isolates was inferred from direct
      sequencing. The previously described important amino acid stretches and positions
      in NS5A were compared between the resistant and sensitive groups. Although some
      variations were observed, no clear differences could be directly correlated with
      the interferon sensitivity. However, sensitive strains were different, owing to
      more amino acid changes when compared to a consensus sequence from all strains.
      The carboxy-terminal region and especially the previously reported NS5A/V3 region
      showed most of the variations. Moreover, the conformational analysis of NS5A by
      secondary structure prediction allowed the differentiation of most sensitive
      strains from resistant ones. It was concluded that other regions different from
      ISDR were involved in resistance to interferon maybe via the interaction between
      NS5A and PKR.

PMID- 9634078
TI  - Infection of a chimpanzee with hepatitis C virus grown in cell culture.
AB  - Culture supernatant harvested from Daudi cells, a lymphoplastoid cell line, after
      58 days of infection with the H77 strain of hepatitis C virus (HCV), was
      inoculated into a chimpanzee. HCV RNA, as detected by RT-PCR, first appeared in
      the serum and liver 5 and 6 weeks, respectively, after inoculation. Peripheral
      blood mononuclear cells (PBMC) collected on week 7 were also positive for HCV
      RNA. The major sequences of hypervariable region 1 (HVR1) of the viral genome
      recovered from the inoculated chimpanzee were the ones which were the majority in
      the original H77 inoculum and not those which were in the majority in the culture
      supernatant. Only the sequence recovered from PBMC was the same as the major one
      found in the cell culture.

PMID- 9634079
TI  - Characterization of determinants involved in the feline infectious peritonitis
      virus receptor function of feline aminopeptidase N.
AB  - Feline aminopeptidase N (fAPN) is a major cell surface receptor for feline
      infectious peritonitis virus (FIPV), transmissible gastroenteritis virus (TGEV),
      human coronavirus 229E (HCV 229E) and canine coronavirus (CCV). By using chimeric
      molecules assembled from porcine, human and feline APN we have analysed the
      determinants involved in the coronavirus receptor function of fAPN. Our results
      show that amino acids 670-840 of fAPN are critically involved in its FIPV and
      TGEV receptor function whereas amino acids 135-297 are essential for the HCV 229E
      receptor function. We also demonstrate that a chimeric molecule assembled from
      human and porcine APN is able to act as a receptor for FIPV. This is surprising
      as neither human nor porcine APN by themselves mediate FIPV infection. These
      results suggest that different determinants in the APN protein are involved in
      mediating the coronavirus receptor function.

PMID- 9634080
TI  - The ectodomains but not the transmembrane domains of the fusion proteins of
      subtypes A and B avian pneumovirus are conserved to a similar extent as those of
      human respiratory syncytial virus.
AB  - The fusion glycoprotein (F(B)) gene of five strains of the B subtype of avian
      pneumovirus (APV; turkey rhinotracheitis virus) has been sequenced. The length of
      the F(B) protein was 538 amino acids, identical to that of the F protein of
      subtype A virus, with which it had 74% and 83% overall nucleotide and deduced
      amino acid identities, respectively. The F(B) and F(A) ectodomains had 90% amino
      acid identity, very similar to the 91% identity between the ectodomains of the F
      proteins of subtype A and B human respiratory syncytial virus (HRSV). As with
      HRSV, the F2 polypeptide was less conserved (83% identity) than F1 (94%). In
      contrast to the ectodomain, the transmembrane and cytoplasmic domains of the two
      APV subtypes were much less conserved (30% and 48% identity, respectively) than
      those of HRSV (92% and 87%, respectively). Comparisons within all the genera of
      the Paramyxoviridae (Pneumovirus, Morbillivirus, Paramyxovirus and Rubullavirus)
      show that low amino acid identity between F protein transmembrane domains is a
      feature of different species of virus rather than of strain differences. This may
      indicate that the two subtypes of APV have evolved in different geographical
      regions and/or different avian species. This is the first report of an F gene
      sequence from a subtype B APV.

PMID- 9634081
TI  - Identification of regions of bovine respiratory syncytial virus N protein
      required for binding to P protein and self-assembly.
AB  - The interaction of bovine respiratory syncytial virus (BRSV) nucleocapsid protein
      (N) with itself and phosphoprotein (P) was investigated using the yeast two
      hybrid system. N-P interaction was abolished by any of a series of internal
      deletions or deletions at the C terminus. In contrast, removal of up to 32 amino
      acids from the N terminus had little effect. Interestingly, while removal of the
      C-terminal 32 amino acids ablated interaction, it was largely restored by a
      second deletion removing up to 32 amino acids from the N terminus. Many of these
      interactions of the BRSV N protein demonstrated a pattern that was similar to
      those occurring in the N protein of related viruses. N-N interaction was
      abolished by any of the internal deletions; however, removal of up to 32 amino
      acids from the N terminus or C terminus was tolerated and increased the strength
      of the interaction between the two N proteins.

PMID- 9634082
TI  - A host restriction-based selection system for influenza haemagglutinin
      transfectant viruses.
AB  - During the 1996 influenza epidemic in Vienna we obtained influenza A virus
      specimens (Vienna/47/96, Vienna/81/96) which grow efficiently in African green
      monkey kidney (Vero) cells but not in embryonated chicken eggs. Amplification of
      the specimens in Vero cells resulted in progeny that agglutinated human but not
      chicken erythrocytes. Reassortment analysis suggested that the haemagglutinin
      (HA) might be responsible for the host restriction. Vero cells were infected with
      the Vienna/47/96 virus and then transfected with reconstituted ribonucleoprotein
      complexes containing HA genes from egg-adapted strains. Subsequent selective
      passages in embryonated chicken eggs resulted in selection of transfectant
      viruses, growing in eggs and containing the transfected HAs. The results
      demonstrate that host restriction of the Vero-adapted Vienna/47/96 virus is due
      to its HA. Moreover, the experiments showed that the Vienna/47/96 strain can be
      used as helper virus for reverse genetics experiments.

PMID- 9634083
TI  - Identification and characterization of RNA-binding activities of avian reovirus
      non-structural protein sigmaNS.
AB  - Cytoplasmic extracts prepared from avian reovirus (ARV) strain S1133-infected
      chicken embryo fibroblasts were examined for the presence of RNA-binding proteins
      in order to identify and characterize ARV RNA-binding proteins. Analysis of
      binding activity to poly(A)-Sepharose indicated that infected cells contained
      significant amounts of a protein that co-migrated with ARV protein sigmaNS
      present in total virus-infected cell extracts. Determination of the N-terminal
      amino acid sequence of several peptide fragments generated by V8 protease
      digestion of the poly(A)-Sepharose-purified protein confirmed that this viral
      protein was sigmaNS. Competition assays showed that single-stranded RNA from the
      unrelated avian pathogen infectious bursal disease virus was able to compete for
      binding of sigmaNS to poly(A)-Sepharose. These data suggest that ARV sigmaNS
      binds to single-stranded RNA in a nucleotide sequence non-specific manner and is
      functionally similar to its counterpart specified by mammalian reovirus.

PMID- 9634084
TI  - Roles of vaccinia virus EEV-specific proteins in intracellular actin tail
      formation and low pH-induced cell-cell fusion.
AB  - During vaccinia virus (VV) morphogenesis intracellular mature virus (IMV) is
      wrapped by two additional membranes to form intracellular enveloped virus (IEV).
      IEV particles can nucleate the formation of actin tails which aid movement of
      IEVs to the cell surface where the outer IEV membrane fuses with the plasma
      membrane forming cell-associated enveloped virus (CEV) which remains attached to
      the cell, or extracellular enveloped virus (EEV) which is shed from the cell. In
      this report, we have used a collection of VV mutants lacking individual EEV
      specific proteins to compare the roles of these proteins in the formation of IEV
      and IEV-associated actin tails and fusion of infected cells after a low pH shock.
      Data presented here show that p45-50 (A36R) is not required for IEV formation or
      for acid-induced cell-cell fusion, but is required for formation of IEV
      associated actin tails. In contrast, gp86 (A56R), the virus haemagglutinin, is
      not required for formation of either IEV or IEV-associated actin tails. Data
      presented also confirm that p37 (gene F13L), gp42 (B5R) and gp22-24 (A34R) are
      needed for formation of IEV-associated actin tails and for cell-cell fusion after
      low pH shock. The phenotypes of these mutants were not affected by the host cell
      type as similar results were obtained in a range of different cells. Lastly,
      comparisons of the phenotypes of VV strains Western Reserve, deltaA34R and
      deltaA36R demonstrate that actin tails are not required for low pH-induced cell
      cell fusion.

PMID- 9634085
TI  - African swine fever: a disease characterized by apoptosis.
AB  - The cell tropism, organ distribution and resultant pathology of African swine
      fever were compared in domestic pigs infected with lethal (Malawi) and sublethal
      (Malta) isolates of African swine fever virus (ASFV). After infections with both
      isolates, ASFV was predominantly localized in cells of the mononuclear phagocytic
      system and was not observed in endothelial cells in lymphoid tissue. More severe
      tissue destruction and cell depletion, associated with high levels of infected
      macrophages, were seen in lymphoid tissues from domestic pigs infected with the
      virulent Malawi isolate compared to the less virulent Malta isolate of ASFV. The
      abundant lymphocyte death was caused by apoptosis and not necrosis. In the
      spleen, as early as 3 days post-infection (p.i.), many lymphocytes in the B and T
      cell areas of the white and red pulp were apoptotic. Apoptosis in the T cells of
      the periarteriolar lymphoid sheaths in the spleen, however, occurred later, at 5
      7 days p.i. In lymph nodes apoptosis was observed in T lymphocytes as early as 4
      days p.i. and extended to B lymphocytes in the follicles later in infection. In
      pigs recovered from infection with the sublethal Malta isolate, virus was found
      to persist in lymph nodes and tonsils for up to 48 days p.i. and was located in
      cells, surrounded by apoptotic lymphocytes, in the paracortex of lymph nodes up
      to 32 days p.i. Taken together, these observations suggest that apoptosis of
      uninfected lymphocytes was induced by cytokines or apoptotic mediators released
      from ASFV infected macrophages.

PMID- 9634086
TI  - The pathogenesis of African swine fever in the resistant bushpig.
AB  - Bushpigs and warthogs are natural reservoir hosts of African swine fever virus
      (ASFV) in the wild, showing no clinical signs of disease when infected with the
      same highly virulent isolates of ASFV that induce rapid, haemorrhagic death in
      domestic pigs. In contrast to domestic pigs, infection of bushpigs with Malawi
      isolate results in low levels of virus replication and lymphocyte apoptosis
      within the spleen, and a relatively low spread of virus to other lymphoid
      tissues. However, at 10 days post-infection, a high degree of apoptosis was seen
      in B lymphocytes of the B cell follicles in bushpig lymph nodes. Virus infected
      cells were present amongst the apoptotic B cells of these follicles, suggesting
      that indirect factors released from ASFV infected macrophages signal surrounding
      lymphocytes to enter apoptosis. The susceptibility/resistance of domestic
      pigs/bushpigs to ASFV may serve as a unique veterinary model for the recently
      emerging haemorrhagic disease of man.

PMID- 9634087
TI  - Restricted expression of Epstein-Barr virus (EBV)-encoded, growth transformation
      associated antigens in an EBV- and human herpesvirus type 8-carrying body cavity
      lymphoma line.
AB  - A body cavity lymphoma-derived cell line (BC1), known to carry both Epstein-Barr
      virus (EBV) and human herpes virus type 8 (HHV-8; or Kaposi's sarcoma-associated
      herpesvirus, KSHV), was analysed for the expression of EBV-encoded, growth
      transformation-associated antigens and cellular phenotype by immunofluorescence
      staining, Western blotting, RT-PCR and flow cytometry. A similar phenotypic
      analysis was also performed on another body cavity lymphoma line, BCBL1, that is
      singly infected with HHV-8. Phenotypically, the two lines were closely similar.
      Although both lines are known to carry rearranged immunoglobulin genes, they were
      mostly negative for B-cell surface markers. Both expressed the HHV-8-encoded
      nuclear antigen (LNA1). Similarly to Epstein-Barr nuclear antigen type 1 (EBNA1),
      LNA1 was associated with the chromatin in interphase nuclei and the mitotic
      chromosomes in metaphase. It accumulated in a few well-circumscribed nuclear
      bodies that did not co-localize with EBNA1. BC1 cells expressed EBNA1, LMP2A and
      EBV-encoded small RNAs but not EBNA2-6, LMP1 and LMP2B. They were thus similar to
      type I Burkitt's lymphoma cells and latently infected peripheral B-cells.
      Analysis of the splicing pattern of the EBNA1-encoding message by RT-PCR showed
      that BC1 cells used the QUK but not the YUK splice, indicating that the mRNA was
      initiated from Qp and not from Cp or Wp.

PMID- 9634088
TI  - Analysis of the hexon gene sequence of bovine adenovirus type 4 provides further
      support for a new adenovirus genus (Atadenovirus).
AB  - The putative hexon gene of bovine adenovirus type 4 (BAV-4), encoding 910 amino
      acid residues, has been identified and sequenced. A characteristic codon usage
      biased towards the use of AT-rich triplets was observed. Comparative analysis
      with other hexon sequences detected a high level of amino acid identity in the
      regions corresponding to the pedestals of the hexon. Substitutions, insertions
      and deletions were identified mainly in the variable regions forming the loops
      which are exposed on the outer surface of the virion. In these variable regions,
      BAV-4 shared similarity only with egg drop syndrome (EDS) virus and ovine
      adenovirus isolate 287 (OAV287). The close relationship of these viruses was also
      demonstrated by phylogenetic analysis of the hexon gene. In addition to the two
      groups of the Mastadenovirus and Aviadenovirus genera, a third cluster appeared
      comprising BAV-4, OAV287 and EDS virus.

PMID- 9634089
TI  - Complementation of a fibre mutant adenovirus by packaging cell lines stably
      expressing the adenovirus type 5 fibre protein.
AB  - Adenovirus-based gene therapy vectors now in use cannot be targeted to specific
      cell types in vivo and are immunogenic, properties which limit their clinical
      utility. Improved vectors lacking the genes for viral structural proteins may
      overcome these limitations. We have developed cell lines which stably express the
      adenovirus type 5 (Ad5) fibre protein in its native trimeric form. These cells
      can complement an Ad5 mutant with a defect in the fibre gene, and are capable of
      incorporating the Ad5 fibre into particles of a different Ad serotype. As the
      fibre protein is responsible for the initial binding of virus to cells, packaging
      cell lines expressing different or modified fibre proteins will be useful in
      studying the mechanism by which adenovirus infects different cell types.

PMID- 9634090
TI  - MHC class I molecules are enriched in caveolae but do not enter with simian virus
      40.
AB  - Simian virus 40 (SV40) binds to MHC class I molecules anywhere on the cell
      surface and then enters through caveolae. The fate of class I molecules after
      SV40 binding is not known. Sensitivity of 125I-surface-labelled class I molecules
      to papain cleavage was used to distinguish internalized class I molecules from
      class I molecules remaining at the cell surface. Whereas the caveolae-enriched
      membrane microdomain was found to also be enriched for class I molecules, no
      internalized papain-resistant 125I-surface-labelled class I molecules could be
      detected at any time in either control cells or in cells preadsorbed with
      saturating amounts of SV40. Instead, 125I-surface-labelled class I molecules, as
      well as preadsorbed 125I-labelled anti-class I antibodies, accumulated in the
      medium, coincident with the turnover of class I molecules at the cell surface.
      The class I heavy chains that accumulated in the medium were truncated and their
      release was specifically prevented by the metalloprotease inhibitor 1,10
      phenanthroline. Thus, whereas class I molecules mediate SV40 binding, they do not
      appear to mediate SV40 entry.

PMID- 9634091
TI  - Taxonomic characteristics of fijiviruses based on nucleotide sequences of the oat
      sterile dwarf virus genome.
AB  - Sequence determination of full-length cDNA clones of genomic segments 7-10 (S7
      S10) of oat sterile dwarf fijivirus (OSDV) revealed that the 5' and 3' ends of
      the plus strands of these segments had the same conserved terminal sequences, 5'
      AACGAAAAA and UUUUUUUAGUC 3'. These sequences are similar, but not identical, to
      the conserved terminal nucleotide sequences of the genomic segments of rice black
      streaked dwarf fijivirus (RBSDV) and maize rough dwarf fijivirus (MRDV). The
      coding strands of S7 and S10 each contained two large nonoverlapping open reading
      frames (ORFs), as do RBSDV S7 and S9, MRDV S6 and S8 and Nilaparvata lugens
      reovirus (NLRV; a putative member of Fijivirus) S9. These results strongly
      suggest that the dicistronic nature of certain genomic segments is characteristic
      of fijiviruses. Computer analyses revealed sequence homology between RBSDV S7
      ORF2, MRDV S6 ORF2 and OSDV S7 ORF2, suggesting that this protein is conserved
      among plant fijiviruses. No counterparts were found in the genome of NLRV, which
      is a nonphytopathogenic insect reovirus. Furthermore, phylogenetic trees derived
      from multiple sequence alignments of each of the homologous proteins from OSDV,
      RBSDV, MRDV and NLRV suggest that NLRV did not evolve from either Fijivirus group
      2 (RBSDV and MRDV) or group 3 (OSDV).

PMID- 9634092
TI  - Detection and assignment of proteins encoded by rice black streaked dwarf
      fijivirus S7, S8, S9 and S10.
AB  - The proteins encoded by rice black streaked dwarf fijivirus (RBSDV) genomic
      segments 7-10 (S7-S10) were characterized. Open reading frames (ORFs) from these
      segments were expressed as fusion proteins in Escherichia coli. Antibodies raised
      against the expressed products were used as probes to determine whether the viral
      ORFs encode structural proteins. In Western blots, antibodies to the expressed S8
      and S10 products reacted with a core capsid (65 kDa) and a major outer capsid (56
      kDa) protein, respectively, while none of the antibodies to S7 and S9 products
      reacted with structural proteins. Antisera to RBSDV S7 ORF1 and S9 ORF1 each
      detected a single protein of the predicted size in total protein extracts from
      infected rice plants and viruliferous Laodelphax striatellus. Immunoelectron
      microscopy revealed that antibodies to RBSDV S7 ORF1 and RBSDV S9 ORF1 reacted
      with tubular structures and viroplasm, respectively, in sections of both infected
      maize plants and viruliferous L. striatellus. Antisera to ORF2 of S7 and S9
      failed to detect any proteins in the infected tissue using either Western
      blotting or immuno-electron microscopic techniques.

PMID- 9634093
TI  - Characterization of cis-acting elements affecting strength and phloem specificity
      of the coconut foliar decay virus promoter.
AB  - During replication in its host plant, coconut foliar decay virus (CFDV) remains
      restricted to the phloem tissue. Previous in vivo studies on subgenomic CFDV DNA
      had provided evidence for the phloem specificity of the CFDV promoter. Here, new
      promoter constructs are described which are distinguished by the presence or
      absence of various cis-acting signals and which gave rise to a 16-fold higher
      reporter gene (beta-glucuronidase) activity (reaching 30% of the cauliflower
      mosaic virus 35S promoter) in tobacco protoplasts, while the phloem specificity
      in transgenic tobacco plants was conserved. Surprisingly, the CFDV stem-loop
      structure dramatically influenced transcriptional efficiency. From these studies
      and sequence comparisons with other phloem-specific promoters, cis-signals
      involved in CFDV promoter strength and tissue specificity were identified.

PMID- 9634094
TI  - Defective forms of cotton leaf curl virus DNA-A that have different combinations
      of sequence deletion, duplication, inversion and rearrangement.
AB  - Tobacco and tomato plants inoculated at least 9 months previously with a
      Pakistani isolate of cotton leaf curl virus (CLCuV-PK), a whitefly-transmitted
      geminivirus, contained substantial amounts of circular dsDNA molecules that were
      mostly about half the size of CLCuV-PK dsDNA-A. They appeared to be derived from
      CLCuV-PK DNA-A by various combinations of sequence deletion, duplication,
      inversion and rearrangement and, in a few instances, insertion of sequences of
      unknown origin. Each of ten tobacco plants contained a different predominant form
      of such a defective molecule; however, all the forms contained the intergenic
      region and part of the AC1 (Rep) gene. Some of the forms contained novel open
      reading frames and might have a role in the evolution of variant geminiviruses.
      The defective components were not detected at 3 months after the original culture
      of CLCuV-PK was transmitted by whiteflies (Bemisia tabaci) from cotton to tomato
      but were present after a further 6 months. They were transmitted, along with full
      length DNA-A, between tobacco and tomato plants by grafting and by B. tabaci.

PMID- 9634095
TI  - Use of modified plum pox virus coat protein genes developed to limit
      heteroencapsidation-associated risks in transgenic plants.
AB  - Aphid transmission of a non-aphid-transmissible strain of zucchini yellow mosaic
      virus (ZYMV-NAT) occurs in transgenic plants expressing the plum pox potyvirus
      (PPV) coat protein (CP) gene. Heteroencapsidation has been shown to be
      responsible for this modification in the epidemiological characteristics of the
      infecting virus. In order to prevent this biological risk, several modified PPV
      CP constructs were produced that were designed to interfere with
      heteroencapsidation itself or to block aphid transmission of heteroencapsidated
      virions. These constructs were first expressed in Escherichia coli in order to
      check for the accumulation of pseudo-particles by electron microscopy. Virus-like
      particles (VLPs) were found with the full-length CP and with a PPV CP lacking the
      DAG amino acid triplet involved in aphid transmission. However, no VLPs were
      observed with CP lacking R220, Q221 or D264, amino acids known to be essential
      for the assembly of other potyvirus CPs. Transgenic Nicotiana benthamiana lines
      expressing the different PPV CP constructs were infected with ZYMV-NAT. Aphid
      transmission assays performed with these plants demonstrated that the strategies
      developed here provide an effective means of minimizing the biological risks
      associated with heteroencapsidation.

PMID- 9634096
TI  - Role of the helper component in vector-specific transmission of potyviruses.
AB  - Four aphid species were tested for their ability to transmit tobacco etch (TEV)
      and turnip mosaic (TuMV) potyviruses. Myzus persicae and Aphis gossypii
      transmitted both viruses efficiently from infected plants, whereas Lipaphis
      erysimi transmitted only TuMV and Myzus ascalonicus was a poor or non-transmitter
      of either virus. Similar electrically monitored probing patterns were produced by
      M. persicae, L. erysimi and M. ascalonicus, ruling out behavioural differences as
      the cause of differential transmission. Transmission results similar to those
      from infected plants were obtained when these aphids acquired homologous
      virus/helper component (HC) mixtures through membranes. With heterologous
      virus/HC mixtures, M. persicae remained a highly efficient vector and M.
      ascalonicus a non-vector, but L. erysimi became an efficient vector of TEV if
      acquired in the presence of TuMV HC and A. gossypii transmitted both viruses less
      efficiently when acquired with TuMV HC. Transmission was highly correlated with
      the retention of virus in the stylets, as determined by autoradiography of 125I
      labelled virions. The results show that constituent(s) of or in the food canal of
      different aphid species differ in their ability to interact with specific HCs,
      leading to qualitative or quantitative differences in ability to retain and
      subsequently transmit specific potyviruses.

PMID- 9634097
TI  - Evidence that assembly of a potyvirus begins near the 5' terminus of the viral
      RNA.
AB  - A search for the first region in the genomic RNA of a potyvirus to be
      encapsidated during the assembly of virus particles in vivo has been undertaken.
      Protoplasts were collected at various times after inoculation and fragments of
      viral RNA that were protected from nuclease degradation were isolated from
      extracts and identified by RT-PCR procedures. Nuclease-resistant fragments of
      viral RNA were not detected in protoplasts that had been infected for 30 min.
      However, such fragments were present in protoplasts collected 40 min after
      inoculation and these contained a region at or near the 5' terminus of the viral
      RNA. Protoplasts that had been infected for 45 min or longer contained full
      length viral RNA in a nuclease-resistant form. These results suggest that
      assembly of virus particles begins with the interaction of coat protein subunits
      with the 5' terminal region of progeny viral RNA molecules.

PMID- 9634098
TI  - Citrus psorosis virus: nucleotide sequencing of the coat protein gene and
      detection by hybridization and RT-PCR.
AB  - Citrus psorosis virus (CPV) is a multicomponent ssRNA virus with a coat protein
      of approximately 48 kDa. The viral genome is encapsidated in short and long
      particles that are readily separated by sucrose density-gradient centrifugation.
      CPV particles are spiral filaments that are referred to as spiroviruses (SV). A
      cDNA library of purified short particles from isolate CPV-4 was prepared in a
      Lambda vector and screened for expression of the coat protein gene (CPG) with a
      monoclonal antibody to the coat protein. Sequencing of immunopositive clones
      indicated a single ORF encoding a 49 kDa protein. This ORF, when expressed in E.
      coli, gave a protein identical in size and immunoreactivity to the CPV coat
      protein. A full-length clone of the CPG was transcribed and used in Northern
      hybridization assays to establish that short particle RNA of CPV is negative
      sense and contains the CPG. Moreover, the CPG was not found on RNA extracted from
      long particles or on the sedimentable dsRNA from CPV infected tissue. RT-PCR
      assays were developed for the amplification of a 600 bp fragment of CPG and for
      the complete CPG (1317 bp). The 600 bp fragment from a biologically and
      serologically different isolate, CPV-6, was cloned, sequenced and found to share
      86% (nucleotide) and 96% (amino acid) identity with CPV-4. BLAST analysis of
      sequences from CPV-4 and CPV-6 detected no significant nucleic acid or protein
      similarity with any known viral sequences.

PMID- 9634099
TI  - The nucleotide sequence of satellite tobacco necrosis virus strain C and helper
      assisted replication of wild-type and mutant clones of the virus.
AB  - The complete nucleotide sequence of satellite tobacco necrosis virus strain C
      (STNV-C) was determined. The genome has a similar overall organization to two
      STNV isolates studied previously but differs significantly from them in the
      secondary structure of the translated and untranslated regions (UTRs). STNV-C RNA
      is naturally uncapped and contains 1221 nt: 101 nt in the 5' UTR, 606 nt in the
      capsid protein (CP) coding region and 514 nt in the 3' UTR. Using the known
      sequences of STNV-C and tobacco necrosis virus strain D (TNV-D) RNAs, full-length
      cDNA clones of both RNAs were constructed. Synthetic transcripts derived from
      STNV-C cDNA clones only replicated in plants and protoplasts when co-inoculated
      with TNV-D transcripts. A number of mutant clones in both the 3' and the 5' STNV
      C RNA UTRs were constructed which disrupted putative cis-acting elements
      recognized by helper virus polymerase. Deletion analysis revealed an essential
      requirement of all 3' and 5' proximal sequences in the STNV-C UTRs for
      replication. However, an internal region in the 3' UTR could be deleted without
      loss of infectivity. Likewise, the entire STNV-C CP-encoding region could be
      deleted and replaced with a marker gene of a similar size without loss of
      transcript accumulation in plants.

PMID- 9634100
TI  - The ecdysteroid UDP-glucosyltransferase gene of Autographa californica
      nucleopolyhedrovirus alters the moulting and metamorphosis of a non-target
      insect, the silkworm, Bombyx mori (Lepidoptera, Bombycidae).
AB  - The Autographa californica nucleopolyhedrovirus (AcMNPV) does not infect the
      silkworm and molecular studies on silkworm insusceptibility have not been
      performed. In cultured cells of the silkworm, the expression of viral genes has
      been reported. The expression of AcMNPV genes and their effect in vivo and in
      vitro was studied. In this study, the early gene, the ecdysteroid UDP
      glucosyltransferase (egt) gene of AcMNPV, which inactivates the insect moulting
      hormone by sugar conjugation, was examined to determine whether it would alter
      the growth of the silkworm. Using wild-type (wt) AcMNPV, the egt gene deletion
      virus (vEGTDEL), and the virus carrying the egt promoter-lacZ cassette in vEGTDEL
      (vEGTZ), the egt promoter-driven expression in cultured cells and in
      nonproductive infection of the silkworm was characterized. Infection of cultured
      cells with vEGTZ at three different doses occurred in a single cell manner. When
      budded wt AcMNPV was injected into the fourth and fifth instar larvae, an
      increase in the amount of virus occurred and caused abnormal larval growth, which
      resulted in the prolongation or skipping of the larval instar, premature
      pupation, or death during the pupal stage. For infection of the fourth instar
      larvae, precocious metamorphosis was observed. When the same amount of vEGTDEL
      was injected, the alteration of growth did not occur. These results suggest that
      the egt gene was expressed in the primary infected cells of the silkworm, and
      that the EGT was secreted into the haemocoel, which significantly altered larval
      growth.

PMID- 9634101
TI  - The single-nucleocapsid nucleopolyhedrovirus of Buzura suppressaria encodes a P10
      protein.
AB  - The p10 gene of Buzura suppressaria single-nucleocapsid nucleopolyhedrovirus
      (BusuNPV) was identified by virtue of its localization downstream from the
      Autographa californica (Ac) MNPV p26 homologue. The BusuNPV p10 gene encodes a
      protein of 94 amino acids. The amino acid sequence contains domains
      characteristic of baculovirus P10 proteins, e.g. a coiled-coil domain, a proline
      rich motif and a positively charged C terminus. The highest amino acid homologies
      were found with the Spodoptera littoralis (Spli) NPV and Spodoptera exigua (Se)
      MNPV P10 proteins. An AcMNPV recombinant expressing the BusuNPV P10 formed
      fibrillar structures in the cytoplasm of Spodoptera frugiperda cells. BusuNPV P10
      could not fully replace AcMNPV P10 in its nuclear disintegration function, since
      polyhedra were not efficiently liberated from infected cells late in infection.
      The BusuNPV p26 gene encodes a protein of 263 amino acid residues with 70% amino
      acid similarity with SeMNPV P26. Downstream of the BusuNPV p10 gene, the gene for
      the occlusion-derived virus protein ODVP-6e is located. This is unlike the
      situation in many other NPVs, including SeMNPV, where the p10 gene neighbours the
      p74 gene. The data presented here suggest that although the p10 gene is not
      conserved in sequence, evolutionary pressure preserves the structure of P10 and
      hence its function. These data also indicate that all NPVs, MNPVs as well as
      SNPVs, contain this gene.

PMID- 9634102
TI  - Specificity of multiple homologous genomic regions in Spodoptera exigua
      nucleopolyhedrovirus DNA replication.
AB  - The region upstream of the Spodoptera exigua multicapsid nucleopolyhedrovirus
      (SeMNPV) ubiquitin gene contains four near-identical 68-bp-long palindromic
      repeats. This region, named Sehr6 and located at map unit (m.u.) 88 of the SeMNPV
      genome on pSeEcoRI-2.2, showed structural homology to previously identified
      homologous regions (hrs) in a number of other baculoviruses. Hrs function as
      enhancers of transcription and as putative origins (oris) of baculovirus DNA
      replication. Five additional hrs (Sehr1-Sehr5) were identified on the SeMNPV
      genome by Southern blot hybridization with an 18-bp-long oligonucleotide
      complementary to a sequence conserved within the arms of the four palindromic
      repeats of Sehr6. Sehr1-Sehr6 were dispersed on the SeMNPV genome at m.u. 8.0,
      30.0, 38.5, 51.0, 77.0 and 88.0, respectively. Sequence analysis of these hrs
      confirmed the presence of palindromic repeats, highly similar to those found in
      pSeEcoRI-2.2. The number of palindromes varied from one (Sehr4) to nine (Sehr1)
      per hr. The Sehrs are all present in non-coding regions of the SeMNPV genome and
      also contain multiple putative transcription recognition sequences. Plasmids
      containing either of the Sehrs replicated in an SeMNPV-dependent DNA replication
      assay. The Sehrs were unable to replicate in an AcMNPV-dependent DNA replication
      assay. This was in contrast to the previously observed SeMNPV non-hr type ori,
      which replicated in the presence of both AcMNPV and SeMNPV. These data suggest
      that the replication of SeMNPV and the role of hrs in this process is highly
      specific.

PMID- 9634103
TI  - Alcoholism in the later years.

PMID- 9634104
TI  - Geriatrics photo quiz. Meningioma.

PMID- 9634105
TI  - Purple patches on the legs.

PMID- 9634106
TI  - Atrial fibrillation: drug therapies for ventricular rate control and restoration
      of sinus rhythm.
AB  - Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and its
      prevalence increases with age. Etiologies include coronary artery disease,
      hypertension, valvular heart disease, thyrotoxicosis, and other cardiac and
      noncardiac conditions. AF can lead to reversible impairment of left ventricular
      (LV) function, LV dilatation, clinical heart failure, angina pectoris, stroke,
      and increased mortality. Digoxin, beta blockers, or calcium channel blockers are
      used to control ventricular rate in new-onset AF with hemodynamically stable
      rhythm and in chronic AF where rhythm cannot be restored. These drugs can be used
      alone or in combination, depending on the clinical situation. The most complete
      relief of symptoms occurs when sinus rhythm is restored. Class IA, IC, and III
      antiarrhythmic agents can be used to restore and maintain sinus rhythm in
      selected patients.

PMID- 9634107
TI  - PACE: a model for integrated care of frail older patients. Program of All
      inclusive Care for the Elderly.
AB  - The Program of All-inclusive Care for the Elderly (PACE) is a model of care that
      pools Medicare and Medicaid funds to provide acute and long-term care services
      for older patients through the use of interdisciplinary teams. Services include
      physician visits, prescription drugs, rehabilitation services, personal care
      workers, hospitalization, and nursing home care, if needed. PACE programs may
      also offer social services intervention, case management, respite care, or
      extended home care nursing. The PACE site assumes financial responsibility for
      all services. Now that PACE programs can become permanent providers under
      Medicare, their number is expected to grow.

PMID- 9634108
TI  - Geriatric rhinitis: what it is, and how to treat it.
AB  - In the nose, normal physiologic changes of aging include loss of nasal tip
      support, atrophy of mucus-producing mucosal glands, and decreased olfaction.
      These changes contribute to geriatric rhinitis, the symptoms of which are often
      attributed by the older patient to "allergies" or "sinus trouble." An
      understanding of these anatomic changes, linked with a thorough history and
      physical examination, allows the physician to properly manage geriatric rhinitis.
      Medical management most often involves liquifying--not drying--nasal secretions
      with oral and topical preparations. Conservative surgical treatment is
      occasionally indicated.

PMID- 9634109
TI  - Chilaiditi's syndrome: an unusual cause of chest or abdominal pain.

PMID- 9634110
TI  - Benefits of screening mammography: a review for the primary care physician.
AB  - BACKGROUND: Screening mammography, particularly for women in their 40s, has
      become a confusing issue for many physicians. Recent scientific and political
      controversies regarding screening guidelines have added to this confusion.
      METHODS: Many randomized clinical trials have shown the benefits of mammographic
      screening for women over the age of 50, and recent studies show a statistically
      significant benefit for women in their 40s as well. Understanding the screening
      controversy requires an understanding of the principle of screening for disease,
      the epidemiology of breast cancer, and the results of the many randomized
      clinical trials, particularly recent data from the Swedish two-county trials. An
      appreciation of the improvements in mammographic quality in recent years, and in
      the education of the radiologists who interpret these studies, will also heighten
      clinical acceptance of this screening technique. RESULTS: Both the American
      Cancer Society and American College of Radiology endorse annual mammographic
      screening for women over age 40, and there is compelling evidence to support
      these recommendations. CONCLUSION: Radiologists, primary care providers,
      surgeons, and pathologists should work together to enhance the benefits of and
      access to screening mammography.

PMID- 9634111
TI  - Disability law: problems and proposals.
AB  - BACKGROUND: Medically disabled persons have traditionally encountered obstacles
      when seeking and maintaining employment. Integration of the medically disabled
      worker is the goal of recent legislation that directs removal of physical
      barriers and protects disabled workers from discrimination. The major force
      driving this social policy is the Americans With Disabilities Act (ADA). METHODS:
      Current disability laws and related judicial opinions are reviewed. Primary
      attention is focused on the ADA. RESULTS: Legislation addressing employment
      discrimination has serious deficiencies. Medical support of this important social
      policy is hampered by vague statutory definitions and seemingly capricious
      judicial opinions. CONCLUSION: Disability laws require precise language
      identifying specific, qualifying medical conditions. The laws should require
      comprehensive medical assessment that objectively establishes a connection
      between a medical disorder and severe, sustained impairment. Some currently
      included conditions, such as personality disorders, should be considered for
      exclusion.

PMID- 9634112
TI  - Does the proven benefit of mammography extend to breast cancer patients over age
      70?
AB  - BACKGROUND: Prospective randomized studies show reduced breast cancer mortality
      among women offered mammographic screening; yet, few women 70 or older were
      represented in these trials. We examine the impact of mammography on stage at
      diagnosis of breast cancer, over the years when mammography came into general
      use, comparing women aged 40 to 69 with those aged 70 and older. METHODS: We
      reviewed the records of 1,001 consecutive patients 40 and older treated for
      invasive or in situ breast cancer in the surgical practice of one of us (H.S.C.)
      between 1979 and 1993, comparing trends in mammography use, means of diagnosis,
      tumor size, axillary node status, and pathology. RESULTS: The proportion of cases
      diagnosed by mammography increased over time to a comparable degree in both age
      groups, as did the proportion of T1 and DCIS or microinvasive cancers. This trend
      toward earlier stage appears entirely due to an increasing use of mammography.
      CONCLUSION: The potential benefit of regular mammography to healthy women aged 70
      and older may equal that observed in their younger counterparts.

PMID- 9634113
TI  - Dynamic magnetic resonance imaging in evaluating suspicious breast lesions:
      correlation with pathologic findings.
AB  - BACKGROUND: We used dynamic magnetic resonance imaging (MRI) to study breast
      lesions in 13 women. METHODS: We observed differences in contrast uptake between
      benignancy and malignancy in 14 suspicious breast lesions. Three-dimensional (3D)
      gradient echo sequences were obtained before and after administration of
      gadolinium-based contrast medium (0.16 mmol/kg). The percentage of signal
      increase in lesions was measured in a series of five 90-second sequences, and
      time-enhancement patterns were correlated with pathologic diagnoses. RESULTS:
      Seven benign lesions and three breast cancer recurrences showed less than 185%
      signal increase at 90 seconds after contrast administration. Three new breast
      cancers and one recently biopsied benign lesion showed more than 185% signal
      increase at 90 seconds. CONCLUSION: Using this MRI technique, we can discriminate
      between new breast cancers (more than 185% early signal increase) and breast
      cancer recurrence and/or benign lesions (less than 185% early signal increase)
      but cannot distinguish recurrent from benign lesions.

PMID- 9634114
TI  - Risk factors for hip fracture among southern older women.
AB  - BACKGROUND: Older women are considered at risk for hip fracture; fracture rates
      are highest in the southern region of the United States. The purpose of this
      study was to develop a predictive model for osteoporotic hip fracture among a
      national sample of southern women aged 50 years and older. METHODS: Subjects were
      participants in the Third National Health and Nutritional Examination Survey,
      Phase 1. Data were collected by the National Center for Health Statistics.
      Predictors examined included age, race, heredity, body mass index, physical
      activity, smoking status, alcohol use, and dairy product use. RESULTS: The sample
      consisted of 953 women aged 50 years and older. The predictive model included
      older age, black race, Hispanic race, and low body mass index. CONCLUSIONS:
      Recommendations emphasize weight gain for underweight women and promotion of
      healthy body weights for women of all ages.

PMID- 9634115
TI  - Implementation of early discharges after uncomplicated vaginal deliveries:
      maternal and infant complications.
AB  - BACKGROUND: Short-stay obstetric stays have been the recent focus of many social
      and medical debates. We did a retrospective study of a large community teaching
      hospital's experience in making a safe transition to short-stay obstetrics.
      METHODS: Over a 10-month period, a multidisciplinary committee developed an
      intrapartum and postpartum education program to allow short hospital stays after
      uncomplicated vaginal deliveries. Computerized data were then retrieved on all
      uncomplicated spontaneous vaginal deliveries (DRG 373) from January 1994 to March
      1995. RESULTS: During the study period, 554 women were discharged on the first
      postpartum day, resulting in three maternal readmissions and nine pediatric
      readmissions (combined readmission rate of 2.2%). This low readmission rate
      compared favorably with our experience with 2,563 uncomplicated vaginal
      deliveries from January 1991 to December 1993, immediately before the institution
      of the short-stay obstetrics program (combined readmission rate of 3.9%). The
      average hospital cost for a 1-day stay was $1,714 compared with $2,477 for a 2-
      to 3-day stay, representing a saving of only 31%. CONCLUSIONS: Early obstetric
      discharges after an uncomplicated spontaneous vaginal delivery can be safe and
      effective with appropriate patient selection and support.

PMID- 9634116
TI  - HIV-1-associated Kaposi's sarcoma in a predominantly black population at an inner
      city hospital.
AB  - BACKGROUND: Kaposi's sarcoma (KS) associated with human immunodeficiency virus
      type 1 (HIV-1) is the most common malignancy in patients with AIDS. It has been
      most commonly reported in white homosexual men, though a few cases have been
      reported in blacks. METHODS: We conducted a retrospective analysis of all HIV-1
      seropositive patients with biopsy-proven KS seen at Howard University Hospital
      between February 1985 and June 1995. RESULTS: Of the 73 patients identified, 66
      (90%), 4 were white, 2 were Hispanic, and 1 was of unidentified race. The median
      age was 32 years. Forty-eight (66%) were homosexual or bisexual men, and 10 (14%)
      were homosexual or bisexual with a history of intravenous drug use (IDU). A
      history of IDU or blood transfusion was the only risk factor in 7 (9%) and 2
      (3%), respectively. The other 6 (8)% were heterosexual. The median survival was
      2.2 years. A CD4 count <200 and the presence of an opportunistic infection were
      associated with shortened survival. CONCLUSIONS: The predominant risk factor for
      HIV-1-associated KS was homosexual or bisexual activity. Only a few women with KS
      were identified, and they also reported sexual transmission from male bisexuals
      and/or drug users. Poor survival was associated with CD4 <200, stage III and IV
      KS at presentation, and opportunistic infections.

PMID- 9634117
TI  - The level of preventive health care in an internal medicine residency clinic:
      still only an ounce of prevention?
AB  - BACKGROUND: Clinical prevention is a critical component of primary care residency
      training. How well residents do preventive services is one measure of the
      adequacy of their training. METHODS: To assess the level of preventive health
      care in a university internal medicine residency clinic, we conducted a
      randomized retrospective review of 225 patient records. RESULTS: We documented
      preventive services in only 39% of potentially appropriate instances. Cholesterol
      screening occurred in 53% of eligible cases, breast examination in 41%, mammogram
      in 69%, Papanicolaou's smear in 53%, estrogen replacement therapy (ERT) in 41%,
      fecal occult blood testing in 30%, flexible sigmoidoscopy in 18%, influenza
      vaccination in 65%, pneumococcal vaccination in 44%, and tetanus immunization in
      only 9%. Male residents were significantly less likely than females to order
      mammograms or offer ERT. CONCLUSIONS: Compared to earlier studies of similar
      design, we found that the level of preventive health care has improved during
      residency training, but remains unacceptably low.

PMID- 9634118
TI  - Maternity care practices of navy family practice residency graduates after
      leaving the military.
AB  - BACKGROUND: Nationwide, 32% of residency-trained family physicians deliver babies
      compared with 73% to 90% in the military. This study describes and defines issues
      that could ultimately help revive family practice maternity care. METHOD: We
      surveyed 112 family physicians who had left the navy. RESULTS: Ninety-one percent
      had delivered babies in the navy, 45% since leaving the military, and 25%
      currently. Principal maternity care incentives both in and out of the military
      were personal and professional satisfaction. Reasons for not providing civilian
      maternity care included malpractice risks, insurance costs, and lifestyle issues.
      The decision for providing maternity care was usually made before or during
      residency, whereas the decision against was most often made upon leaving the
      military. Among more recent graduates (1990-1995), 48% continued to deliver
      babies in civilian practice. (This is about 20% more than recent civilian
      graduates.) Malpractice concerns were less important to this group than to
      earlier graduates. CONCLUSIONS: Factors discouraging family physicians from
      providing maternity care arise from their practice environment and are not easily
      overcome with improved training and experience. Recent navy residency graduates
      are not as easily discouraged.

PMID- 9634119
TI  - Patient-controlled anesthesia for colonoscopy using propofol: results of a pilot
      study.
AB  - BACKGROUND: We studied the feasibility of using patient-controlled anesthesia
      (PCA) for conscious sedation during colonoscopy. METHODS: Patients having
      elective colonoscopy had medications delivered in bolus fashion by PCA pump
      (Abbot Lifecare Provider 5500 Infusion System). Four patients received propofol
      as 20 mg/dose boluses, and four patients received propofol in a 0.3 mg/kg/dose.
      Twelve patients received propofol at 0.2 mg/kg/dose with alfentanil at 4
      microg/kg/dose. RESULTS: There were no clinically unacceptable changes in
      continuously monitored blood pressure, pulse rate, ECG, or respiratory rate.
      There were no adverse effects from the sedation and no complications due to
      colonoscopy. Recovery time was rapid, but recall persisted in most subjects. Pain
      and overall discomfort in patients given propofol only were rated as moderate by
      most subjects. CONCLUSION: Patient-controlled anesthesia is feasible for use in
      endoscopic sedation. Propofol alone did not allow adequate pain relief, but
      propofol and alfentanil together seemed to provide good control of pain.

PMID- 9634120
TI  - The red eye revisited: ophthalmia nodosa due to tarantula hairs.
AB  - We present the case of a 17-year-old girl who came to our center with a red
      irritated eye from exposure to tarantula hairs. An ophthalmology literature
      search revealed six reported cases. There have been no reports of these cases in
      the general medical and pediatric literature. Due to the increasing popularity of
      tarantulas as pets, we present the following case report and discussion to bring
      attention to this potential complication of tarantula handling.

PMID- 9634121
TI  - Colonic strictures induced by nonsteroidal anti-inflammatory drugs.
AB  - Long-term use of nonsteroidal anti-inflammatory drugs has been reported to cause
      small bowel and colonic ulcerations and strictures. Abdominal pain, change in
      bowel habits, and anemia are frequently present, mimicking other inflammatory and
      neoplastic diseases of the gut. We report two cases of drug-induced colonic
      stricture that illustrate two different spectrums of this disease. The first is a
      case of ascending colon ulcerated strictures and severe anemia managed
      conservatively, and the second is a chronic variant with obstructive-type
      symptoms and a tight nonulcerated colonic stricture that necessitated right
      hemicolectomy.

PMID- 9634122
TI  - Prolonged prostate-specific antigen response in flutamide withdrawal syndrome
      despite disease progression.
AB  - Flutamide withdrawal syndrome is characterized by a decrease in prostate-specific
      antigen (PSA) after flutamide withdrawal in a subset of patients with progressing
      metastatic carcinoma of the prostate. It is generally hypothesized to be due to a
      point mutation in the androgen receptor that allows the antiandrogen to function
      as an agonist, leading to a dramatic and rapid PSA response. We describe a
      patient with androgen-independent prostate cancer in whom PSA continued to
      decrease for a period of 15 months after flutamide withdrawal. With continuing
      fall in PSA, the patient had unequivocal progression of disease seen on bone
      scan. This case illustrates the potential decoupling of PSA response from disease
      status in flutamide withdrawal. It also illustrates the need for continued
      clinical evaluation of patients with metastatic prostate cancer, even in the face
      of PSA response.

PMID- 9634123
TI  - Cavernous sinus syndrome due to metastatic renal cell carcinoma.
AB  - We describe a 49-year-old woman with a history of metastatic renal cell carcinoma
      and classic signs and symptoms of left-sided cavernous sinus syndrome. Magnetic
      resonance imaging showed a lesion in the left cavernous sinus consistent with
      metastatic renal cell carcinoma. The patient received radiation therapy totaling
      4,600 cGy, with complete resolution of symptoms. This represents the first case
      report of renal cell carcinoma metastatic to the left cavernous sinus.

PMID- 9634124
TI  - Schistosomiasis of the urinary bladder in an African immigrant to North Carolina.
AB  - A 30-year-old black man came to the emergency department with gross hematuria,
      prostatitis, and urethritis 4 months after immigrating to this country from the
      Sudan in Africa. Urinalysis revealed hematuria and no ova or parasites. An
      intravenous urogram showed normal kidneys and ureters. The patient had cystoscopy
      with biopsies of an inflamed and ulcerated bladder mucosa. The nematode
      Schistosoma haematobium and schistosome eggs were identified without evidence of
      urothelial malignancy. The patient was treated with praziquantel and is currently
      asymptomatic. Over 200 million people are infected with schistosomiasis
      worldwide, yet this disease is rarely encountered in this country. The
      differential diagnosis and assessment of patients must include exposure to
      uncommon diseases that are endemic to other geographic regions.

PMID- 9634125
TI  - CD5 negative diffuse mantle cell lymphoma with splenomegaly and bone marrow
      involvement.
AB  - We report the case of a 78-year-old man in whom routine physical examination
      revealed cervical adenopathy and splenomegaly. Peripheral blood showed a normal
      white blood cell count with an absolute lymphocytosis, which included a
      population with slightly indented nuclei. Lymph node biopsy showed morphology
      compatible with mantle cell lymphoma. Bone marrow biopsy showed replacement by a
      lymphoid proliferation composed of lymphocytes with features similar to those
      found in the peripheral blood. Immunophenotypic analysis of both peripheral blood
      and lymph node showed positivity for CD19, CD20 and CD22, with lambda light chain
      restriction. Tests for CD5 and CD10 were negative. Cytogenetic analysis and
      polymerase chain reaction studies confirmed the presence of t(11,14) supporting a
      diagnosis of mantle cell lymphoma. This unusual case of CD5-negative mantle cell
      lymphoma exemplifies the importance of combined molecular, cytogenetic, and
      morphologic evaluation when confronted with a lymphoma having an atypical
      phenotype.

PMID- 9634126
TI  - Laryngeal manifestations of vasculitic disease.
AB  - Vasculitis can involve the larynx in 4% to 10% of cases and can cause arthritis,
      edema, or upper airway obstruction within the larynx. Since most of these
      laryngeal manifestations are nonspecific, the clinician needs to keep a high
      index of suspicion when a patient complains of hoarseness or laryngeal discomfort
      and chronic constitutional symptoms. We present a case of crescentic
      glomerulonephritis associated with antineutrophil crytoplasmic autoantibody
      (ANCA). In addition, we discuss the usefulness and indications of ANCA serology
      and review multiple laryngeal manifestations that have been associated with
      common vasculitides and reported in the medical literature.

PMID- 9634127
TI  - Endometrial stromal sarcoma with sex cord-like differentiation associated with
      tamoxifen therapy.
AB  - Low-grade endometrial stromal sarcoma with sex cord-like differentiation occurred
      in two postmenopausal patients who had received tamoxifen for more than 3 years
      after surgical resection for breast cancer. Uterine sarcomas have been described
      in association with the use of tamoxifen. Only two cases of endometrial stromal
      sarcoma with sex cord-like features associated with tamoxifen use have been
      reported previously. This report adds an additional two cases of this tumor.
      Immunohistochemical and ultrastructural examinations of the tumor support the
      concept of smooth muscle differentiation in the sex cord-like areas. This
      observation proposes that the low-grade endometrial stromal sarcoma with sex cord
      like elements may be a consequence of tamoxifen ingestion, but the exact
      mechanism of tamoxifen in the development of this tumor remains speculative.

PMID- 9634128
TI  - Sunscreens and skin cancer.

PMID- 9634129
TI  - Intermittent fever and pancytopenia.

PMID- 9634130
TI  - Giant skin cancers.

PMID- 9634131
TI  - Social anxiety among adolescents: linkages with peer relations and friendships.
AB  - This study examined the utility of modifying the Social Anxiety Scale for
      Children-Revised (SASC-R) for use with adolescents, and examined associations
      between adolescents' social anxiety (SA) and their peer relations, friendships,
      and social functioning. Boys (n = 101) and girls (n = 149) in the 10th through
      12th grades completed the Social Anxiety Scale for Adolescents (SAS-A) and
      measures of social support, perceived competence, and number and quality of their
      best friendships. Factor analysis of the SAS-A confirmed a three-factor
      structure: Fear of Negative Evaluation, Social Avoidance and Distress in General,
      and Social Avoidance Specific to New Situations or Unfamiliar Peers. Girls
      reported more SA than boys, and SA was more strongly linked to girls' social
      functioning than boys'. Specifically, adolescents with higher levels of SA
      reported poorer social functioning (less support from classmates, less social
      acceptance), and girls with higher levels of SA reported fewer friendships, and
      less intimacy, companionship, and support in their close friendships. These
      findings extend work on the SASC-R to adolescents, and suggest the importance of
      SA for understanding the social functioning and close friendships of adolescents,
      especially girls.

PMID- 9634132
TI  - The development of early externalizing problems among children from low-income
      families: a transformational perspective.
AB  - The present study examined pathways leading to early externalizing problems from
      age 1 to 3 1/2 in a design that took advantage of our knowledge of normative
      progression and normative socialization as well as findings from research on
      risk. A sample of 130 low-income participants was followed longitudinally from 12
      to 42 months using observational measures of developmentally salient parenting
      and child disruptive behavior to predict early externalizing problems. Results
      are best accommodated by concepts such as transformation and transaction from
      developmental psychology. For boys, both child and parent variables predicted
      later externalizing. For girls and boys, the interaction between child
      noncompliance and maternal rejection was significant.

PMID- 9634133
TI  - Racial differences on the Conners Teacher Rating Scale.
AB  - Factor congruence and mean differences on the Conners Teacher Rating Scale were
      assessed across African-American and Caucasian school children. Factor analyses
      conducted separately by gender revealed similar factors across races for males
      and females. The main differences in factor structure within gender were the
      presence of an Antisocial factor in black males and an Inattention factor in
      white females. Across both males and females, teachers tended to rate black
      children higher than white children on factors relating to externalizing
      behaviors. Whether mean differences are a result of teacher bias or actual
      behavioral differences in the classroom needs further research.

PMID- 9634134
TI  - Cumulative risk across family stressors: short- and long-term effects for
      adolescents.
AB  - This study examined the relationship between number of family risk factors during
      adolescence and three areas of psychosocial adjustment (internalizing problems,
      externalizing problems, and academic achievement) in adolescence and 6 years
      later in young adulthood. Risk factors examined included parental divorce,
      interparental conflict, maternal physical health problems, maternal depressive
      mood, and mother-adolescent relationship difficulties. The findings indicated
      both concurrent and long-term associations between number of family risk factors
      and psychosocial adjustment; however, the results differed based on area of
      adjustment examined and whether concurrent or longitudinal data were considered.
      Furthermore, a steep increase in adjustment difficulties occurred when number of
      risk factors increased from three to four. The results are discussed in the
      framework of four hypotheses which were tested, and clinical implications are
      delineated.

PMID- 9634135
TI  - Determinants of harsh parenting in Mexico.
AB  - This paper presents a structural model of the determinants of harsh parenting
      among Mexican mothers. One hundred five mothers (46 from the community; 59
      referred to agencies for child maltreatment) were recruited from Sonora
      (Northern) Mexico and interviewed. In this model the use of physical punishment
      was explained by (1) authoritarian parenting style (mothers' beliefs concerning
      the effective use of physical punishment and mothers' lack of disciplinary
      skills) and (2) family dysfunction (a latent variable constructed from reports of
      interspousal violence and the parents' use of alcohol and drugs). In addition,
      the indirect effects of demographic and historical variables on harsh parenting
      was included. The findings show that the most important factor influencing the
      use of physical punishment in these families was authoritarian parenting style,
      exerting a significant direct effect on the mothers' reports of their use of
      harsh punishment. Family dysfunction had an indirect effect through parenting
      style. Some sociodemographic variables also indirectly influenced the use of
      beliefs maternal punishment It is concluded that cultural beliefs play a major
      role in parenting within the framework of Mexican family relations.

PMID- 9634136
TI  - Obtaining systematic teacher reports of disruptive behavior disorders utilizing
      DSM-IV.
AB  - This study examines the psychometric properties of the Vanderbilt AD/HD
      Diagnostic Teacher Rating Scale (VADTRS) and provides preliminary normative data
      from a large, geographically defined population. The VADTRS consists of the
      complete list of DSM-IV AD/HD symptoms, a screen for other disruptive behavior
      disorders, anxiety and depression, and ratings of academic and classroom behavior
      performance. Teachers in one suburban county completed the scale for their
      students during 2 consecutive years. Statistical methods included (a) exploratory
      and confirmatory latent variable analyses of item data, (b) evaluation of the
      internal consistency of the latent dimensions, (c) evaluation of latent structure
      concordance between school year samples, and (d) preliminary evaluation of
      criterion-related validity. The instrument comprises four behavioral dimensions
      and two performance dimensions. The behavioral dimensions were concordant between
      school years and were consistent with a priori DSM-IV diagnostic criteria.
      Correlations between latent dimensions and relevant, known disorders or problems
      varied from .25 to .66.

PMID- 9634137
TI  - The relationship between peer status and depressive symptoms in children and
      adolescents.
AB  - The purpose of this study was to examine the relationship between specific
      symptoms of depression and particular styles of peer difficulties. Participants
      were 1687 students in fourth, sixth, seventh, eighth, ninth, and eleventh grades
      from a midsized Midwestern city. Based on previous studies, it was hypothesized
      that rejected and neglected youths would report greater depressive symptomatology
      than other peers. In addition, aggressive-rejected youth were predicted to report
      more Interpersonal Problems while submissive-rejected youths were expected to
      report more Anhedonia. There were no sociometric group differences on global
      scores of depression as measured by the Children's Depression Inventory; however,
      the aggressive- and submissive-rejected youths did report specific differences.
      Aggressive-rejected youths reported more Interpersonal Problems and feelings of
      Ineffectiveness, while the neglected and submissive-rejected youths reported more
      Anhedonia. Taken together, such differences provide support for differentiating
      among types of rejected students and suggest that different interventions may be
      necessary to address the needs of these youths.

PMID- 9634138
TI  - Anatomical and neurochemical definition of the nucleus of the stria terminalis in
      Japanese quail (Coturnix japonica).
AB  - This study in birds provides anatomical, immunohistochemical, and hodological
      data on a prosencephalic region in which the nomenclature is still a matter of
      discussion. In quail, this region is located just dorsal to the anterior
      commissure and extends from the level of the medial part of the preoptic area at
      its most rostral end to the caudal aspects of the nucleus preopticus medialis. At
      this caudal level, it reaches its maximal elongation and extends from the ventral
      tip of the lateral ventricles to the dorsolateral aspects of the paraventricular
      nucleus. This area contains aromatase-immunoreactive cells and a sexually
      dimorphic population of small, vasotocinergic neurons. The Nissl staining of
      adjacent sections revealed the presence of a cluster of intensely stained cells
      outlining the same region delineated by the vasotocin-immunoreactive structures.
      Cytoarchitectonic, immunohistochemical, and in situ hybridization data support
      the notion that this area is similar and is probably homologous to the medial
      part of the nucleus of the stria terminalis of the mammalian brain. The present
      data provide a clear definition of this nucleus in quail: They show for the first
      time the presence of sexually dimorphic vasotocinergic neurons in this region of
      the quail brain and provide the first detailed description of this region in an
      avian species.

PMID- 9634140
TI  - Dual morphology and topography of the corticothalamic terminals originating from
      the primary, supplementary motor, and dorsal premotor cortical areas in macaque
      monkeys.
AB  - In the motor, somatosensory, and auditory systems of rodents and cats, the
      corticothalamic connection is composed of a main projection formed by small
      endings and a minor projection terminating with giant endings. To establish
      whether the corticothalamic projection originating from motor cortical areas in
      primates exhibits the same duality, the anterograde tracer biotinylated dextran
      amine was injected in eight macaque monkeys in the primary motor (M1; n = 3), the
      supplementary motor (SMA; n = 3) and the dorsal premotor (PMd; n = 2) cortical
      areas to label corticothalamic axons. The corticothalamic projection originating
      from these three motor cortical areas was characterized by the presence of axon
      terminals constituting the same two types of endings, observed both as boutons en
      passant and terminaux. The population of small endings exhibited a mean cross
      sectional maximum diameter of 0.95 microm (S.D. = 0.23), a range of diameters not
      overlapping that of giant endings (mean diameter = 3.46 microm, S.D. = 0.74
      microm). Topographically, the giant endings originating from M1 were located in
      the same thalamic nucleus (ventroposterolateral nucleus, oral part) in which the
      small endings were found. In contrast, the giant endings originating from SMA and
      PMd were located in a thalamic nucleus (mediodorsal nucleus) distinct from the
      main termination zone formed by small endings. Along the rostrocaudal axis, the
      giant endings were distributed in a restricted zone, irrespective of the origin
      of the projection (M1, SMA, PMd). The dual morphology of corticothalamic endings,
      previously found in rodents and cats, is present in the motor system of subhuman
      primates for both primary and nonprimary motor cortical areas.

PMID- 9634139
TI  - Characterization of spinal motoneuron degeneration following different types of
      peripheral nerve injury in neonatal and adult mice.
AB  - Experimental lesions have been used widely to induce motoneuron (MN) degeneration
      as a model to test the ability of different trophic molecules to prevent lesion
      induced alterations. However, the morphological mechanisms of spinal MN death
      following different types of lesions is not clear at the present time. In this
      study, we have characterized the morphological characteristics of MN cell death
      by examining DNA fragmentation and the ultrastructural and light microscopic
      morphological features of MNs following different types of spinal nerve injury
      (i.e., axotomy and avulsion) in the developing and adult mouse. In neonatal mice,
      axotomy induced cell death as well as the atrophy of MNs that survived the
      injury. DNA fragmentation could be detected by using the terminal
      deoxynucleotidyl transferase (TUNEL) method during the cell death process
      following neonatal axotomy, whereas TUNEL labeling was not observed following
      either neonatal or adult avulsion. However, with the exception of TUNEL labeling,
      the morphological characteristics of MN death following neonatal axotomy and
      avulsion were similar, and both resembled most closely the form of programmed
      cell death termed cytoplasmic or type 3B, which exhibits similarities as well as
      differences with currently accepted definitions of apoptosis. By contrast, adult
      avulsion resulted in a type of degeneration that resembled necrosis more closely.
      However, even there, the morphology was mixed, showing characteristics of both
      apoptosis and necrosis. These results indicate that the mode of MN degeneration
      is complex and is related to developmental age and type of lesion.

PMID- 9634141
TI  - Seasonal plasticity and sexual dimorphism in the avian song control system:
      stereological measurement of neuron density and number.
AB  - Differences in neuron density and number are associated with seasonal plasticity
      and sexual dimorphism in the avian song control system. In previous studies,
      neuron density and number in this system have been quantified primarily through
      nonstereological approaches in thick tissue sections by using the nucleolus as
      the unit of count. The reported differences between seasons and sexes may be
      inaccurate due to biases introduced by neuron splitting during sectioning. We
      used the unbiased optical disector technique on tissue from three previous
      studies (two investigations of seasonal plasticity and one investigation of
      sexual dimorphism in avian song nuclei) to assess seasonal and sex differences in
      neuron density and number. In two song nuclei, HVc and the robust nucleus of the
      archistriatum (RA), the optical disector yielded intergroup differences in neuron
      density and number that coincided well with the three previous reports. We also
      estimated neuron number and density with a random, systematic, nonstereological
      counting protocol that used the neuronal nucleolus as the unit of count. We
      compared this method directly to the optical disector. In all cases, the two
      neuron-counting methods produced similar estimates of neuron number and density;
      the differences between treatment groups were equally discernible regardless of
      the counting method used. This study confirms previously reported seasonal and
      sex differences in the HVc and the RA by use of stereology and indicates that a
      random, systematic, nonstereological neuron-counting protocol is accurate and is
      well suited to the study of these phenomena in the avian song control system.

PMID- 9634142
TI  - Induction of MAP1B phosphorylation in target-deprived afferent fibers after
      kainic acid lesion in the adult rat.
AB  - We have previously shown that the phosphorylated form of microtubule-associated
      protein 1B (MAP1B-P), which is located in growing axons during development and
      regeneration, remains detectable in the adult central nervous system only in
      areas that undergo morphologic plasticity (Nothias et al. [1996] J. Comp. Neurol.
      368:317-334). Our objective in the present study was to determine whether lesion
      induced axonal remodeling, in the adult rat, is associated with reinduction of
      MAP1B phosphorylation. MAP1B-P was not detectable in intact adult thalamic
      ventrobasal complex (VB), although low levels of MAP1B and its mRNA were present.
      A neuron-depletion of VB by in situ injection of kainic acid was followed by an
      induction of MAP1B phosphorylation by 24 hours postlesion. MAP1B-P was detected
      in fibers originating from undamaged neurons that were not located in the lesion,
      as demonstrated by the absence of hybridized MAP1B-mRNA. Ultrastructural analysis
      confirmed the exclusive location of MAP1B-P in axons in a proximodistal gradient.
      MAP1B phosphorylation appeared to be regulated by posttranslational modification
      of existing protein because the levels of MAP1B-mRNA did not change. The number
      of MAP1B-P-labeled fibers increased during the first month postlesion and
      remained high for a long period. Double staining by using axonal tracing with
      dextran-biotin and tyrosine hydroxylase immunohistochemistry, showed the presence
      of MAP1B-P in VB afferents from somatosensory relays and the locus coeruleus.
      This study supports the hypothesis that MAP1B, at a particular state of
      phosphorylation, is correlated with axonal remodeling in the adult central
      nervous system (CNS). We suggest that the interaction of MAP1B-P with
      microtubules allows the modulation of their dynamic properties during periods of
      increased axonal plasticity.

PMID- 9634143
TI  - Loss of primary sensory neurons in the very old rat: neuron number estimates
      using the disector method and confocal optical sectioning.
AB  - Loss of neurons has been considered to be a prime cause of nervous disturbances
      that occur with advancing age. However, the notion of a constitutive aging
      related loss of neurons has been challenged recently in several studies that used
      up-to-date methods for counting neurons. In this study, we have applied
      stereological techniques with the objective of obtaining quantitative data on
      total neuron numbers and the distribution of neuron cross-sectional areas in the
      fifth cervical (C5) and fourth lumbar (L4) dorsal root ganglion (DRG) of 3- and
      30-month-old Sprague-Dawley rats. Tissue data were recorded on a confocal laser
      scanning microscope with the use of the optical-disector technique and random,
      systematic sampling. Aged rats of both sexes disclosed only a small decrease
      (approximately 12%) in the number of cervical and lumbar DRG neurons.
      Furthermore, there was no significant correlation between the degree of neuron
      loss and the extent of behavioral deficits among the aged individuals. The DRG
      neurons of aged rats had a smaller mean cross-sectional area (approximately 15%;
      P < 0.001) at both DRG levels. Further analysis of the male cohorts was carried
      out by using isolectin B4 and neurofilament subunit (phosphorylated 200 kDa;
      RT97) immunoreactivity (IR) as selective markers for unmyelinated and myelinated
      axons, respectively, and disclosed no significant change in the relative
      frequencies of immunoreactive neuron profiles in the old rats. However, RT97-IR
      DRG neurons of the aged rats had significantly smaller cross-sectional areas
      (approximately 9% in C5; approximately 16% in L4; P < 0.001) than the young adult
      rats, indicating a selective cell body atrophy among myelinated primary afferents
      during aging. The results indicate that loss of primary sensory neurons cannot
      exclusively explain the functional deficits in sensory perception among senescent
      individuals. It seems likely that other factors at the subcellular level and/or
      target interaction(s) contribute substantially to the sensory impairments
      observed with advancing age.

PMID- 9634144
TI  - Dendritic spines containing mu-opioid receptors in rat striatal patches receive
      asymmetric synapses from prefrontal corticostriatal afferents.
AB  - Prefrontal corticostriatal afferents to the caudate-putamen nucleus (CPN) have
      been implicated in motor and cognitive functions that are subject to opioid
      modulation through the mu-opioid receptor (MOR). We examined the cellular basis
      for this modulation by combining anterograde transport of biotinylated dextran
      amine (BDA) following injections into the rat prefrontal cortex with
      immunocytochemical detection of MOR in patch compartments of the CPN. The BDA
      labeled neurons in deep layer V and layer VI of the dorsal part of the anterior
      cingulate cortex and the medial agranular cortex projected bilaterally, with an
      ipsilateral predominance, to MOR-enriched patches in the dorsomedial and
      dorsocentral CPN, respectively. BDA-labeled terminals often apposed MOR
      immunoreactive dendrites and perikarya but formed exclusively asymmetric,
      excitatory-type synapses mainly with dendritic spines. Of the total anterogradely
      labeled axon terminals forming asymmetric synapses, 40% (151 of 377) were with
      MOR-labeled spines, and 58% (220 of 377) were with unlabeled dendritic spines. In
      addition, immunogold-silver particles for MOR were seen in 14% (134 of 938) of
      all BDA-labeled axons and axon terminals. These dually labeled axon terminals
      also formed asymmetric synapses with dendritic spines that contained MOR
      immunoreactivity. The proportions of BDA-labeled axon terminals forming
      asymmetric synapses with MOR-labeled or unlabeled spines were similar in the CPN
      ipsilateral and contralateral to the cortical injections. These results suggest
      that, in patch compartments of the CPN, MOR plays a critical role in postsynaptic
      response to, but also in presynaptic modulation of, prefrontal corticostriatal
      excitation.

PMID- 9634145
TI  - Metamorphic control of cyclic guanosine monophosphate expression in the nervous
      system of the tobacco hornworm, Manduca sexta.
AB  - During metamorphosis of Manduca sexta, defined sets of neurons show a dramatic
      accumulation of cyclic guanosine monophosphate (cGMP). Although many of these
      cells show low but detectable levels of cGMP during specific developmental
      windows, these levels are enhanced dramatically during dissection of the central
      nervous system (CNS). The ability of these neurons to show this induced cGMP
      expression depends on the developmental stage. Larvae do not show this capacity
      but it appears during the transition from the larval to the pupal stage. There
      are two different classes of response: the early expressing neurons start to show
      a cGMP response at the beginning of the prepupal stage while the late expressing
      cGMP neurons start at different times during the pupal-adult transition. The
      former set includes larval neurons that will likely be remodeled during
      metamorphosis, and a number of them are serotonergic. The late-expressing group
      also includes some larval cells, but most are adult-specific neurons. At least
      for one adult-specific cluster, the antennal lobe neurons, the cGMP expression
      parallels the maturation phase of these cells.

PMID- 9634146
TI  - Sequence and expression of glutamic acid decarboxylase isoforms in the developing
      zebrafish.
AB  - We describe the isolation two glutamic acid decarboxylase (GAD) cDNAs from
      zebrafish with over 84% identity to human GAD65 and GAD67. In situ hybridization
      studies revealed that both GAD65 and GAD67 were expressed in the early zebrafish
      embryo during the period of axonogenesis, suggesting a role for GABA prior to
      synapse formation. Both GAD genes were detected in the telencephalon, in the
      nucleus of the medial longitudinal fasciculus in the midbrain, and at the border
      regions of the rhombomeres in the rostral hindbrain. In the caudal hindbrain,
      only GAD67 was detected (in neurons with large-caliber axons). In the spinal
      cord, both GAD genes were detected in dorsal longitudinal neurons, commissural
      secondary ascending neurons, ventral longitudinal neurons, and Kolmer-Agduhr
      neurons. Immunohistochemistry for gamma-aminobutyric acid (GABA) revealed that
      GABA is produced at all sites of GAD expression, including the novel cells in the
      caudal hindbrain. These results are discussed in the context of the hindbrain
      circuitry that supports the escape response. We conclude that fish, like mammals,
      have two GAD genes. The zebrafish GAD65 and GAD67 are present in identified
      neurons in the forebrain, midbrain, hindbrain, and spinal cord, and they catalyze
      the production of GABA in the developing embryo.

PMID- 9634147
TI  - Regeneration of the newt retina: order of appearance of photoreceptors and
      ganglion cells.
AB  - The adult newt regenerates a functional retina following removal or destruction
      of the original retina. We studied the order of appearance of cell types in the
      regenerating retina by using immunohistochemical techniques. An antibody that
      recognizes the alpha subunit (260 kDa) of voltage-dependent Na+ channels was
      found to label a 255-kDa band in Western blots of crude membrane fractions from
      the normal retina. Cryosections of normal retina revealed intense Na+ channel
      immunoreactivity in somata and axons of ganglion cells, weaker immunoreactivity
      in somata of amacrine cells, and no immunoreactivity in the inner plexiform
      layer. In the same sections, immunoreactivity to a monoclonal antibody (RB-1)
      specific to newt cones was intense in the photoreceptor layer. In regenerating
      retinas, double staining with the Na+ channel antibody as a possible marker of
      ganglion cells and RB-1 antibody first revealed immunoreactive cells at the
      intermediate stage (three to five cells thick), which does not exhibit segregated
      synaptic layers. Na+ channel-immunoreactive ganglion cells appeared before the RB
      1-immunoreactive photoreceptors. Because ganglion cells also appear before
      photoreceptor cells in normal development, common mechanisms may control both the
      generation and the regeneration of the newt retina.

PMID- 9634148
TI  - The need for depot atypical antipsychotics in the U.S.

PMID- 9634149
TI  - Maryland's Medicaid reform: design and development.

PMID- 9634150
TI  - Maryland's Medicaid reform: a provider's perspective.

PMID- 9634151
TI  - Maryland's Medicaid reform: Will the gain outweigh the pain?

PMID- 9634152
TI  - The structure of psychiatrists' outpatient practice.

PMID- 9634153
TI  - The downside of the family-organized mental illness advocacy movement.

PMID- 9634154
TI  - Why consumers and family advocates must work together.

PMID- 9634155
TI  - Cultural sensitivity and aging.

PMID- 9634156
TI  - Policy reform dilemmas in promoting employment of persons with severe mental
      illness.
AB  - Recent evaluations by the U.S. General Accounting Office and the National
      Alliance for the Mentally Ill of reemployment efforts of the federal-state
      vocational rehabilitation program found that services offered by state vocational
      rehabilitation agencies do not produce long-term earnings for clients with
      emotional or physical disabilities. This paper examines reasons for these poor
      outcomes and the implications of recent policy reform recommendations. Congress
      must decide whether to take action at the federal level to upgrade programs
      affecting persons with severe mental illnesses or to continue to rely on state
      decision making. The federal-state program largely wastes an estimated $490
      million annually on time-limited services to consumers with mental illnesses.
      Rechanneled into a variety of innovative and more appropriate integrated services
      models, the money could buy stable annual vocational rehabilitation funding for
      62,000 to 90,000 consumers with severe mental illnesses. Larger macrosystem
      problems involve the dynamics of the labor market that limit job opportunities
      and the powerful work disincentives for consumers with severe disabilities now
      inherent in Social Security Disability Insurance, Supplemental Security Income,
      Medicare, and Medicaid.

PMID- 9634157
TI  - A randomized controlled study of the effectiveness of intensive outpatient
      treatment for cocaine dependence.
AB  - OBJECTIVE: A randomized controlled study design was used to compare the
      effectiveness of intensive outpatient treatment with individual outpatient
      counseling and a combination of individual and group outpatient counseling for
      cocaine-dependent patients. METHODS: Volunteers for this study were recruited
      from among first admissions to an inner-city, public-sector outpatient substance
      abuse clinic. In-treatment, end-of-treatment, and nine-month follow-up
      assessments were compared for participants randomly assigned for 12 weeks to one
      of three treatment modalities--weekly individual outpatient counseling, weekly
      individual counseling plus one weekly group session, or a newly designed
      intensive group treatment program consisting of three hours of group treatment
      three days a week. RESULTS AND CONCLUSIONS: Patients who completed the intensive
      program showed significant improvement from intake to end-of-treatment scores on
      the Addiction Severity Index, the Beck Depression Inventory, and the Symptom
      Checklist. At nine-month follow-up, patients who had remained in treatment longer
      had fewer drug problems, a smaller proportion of positive urine drug screening
      tests, a better employment status, and fewer psychological problems compared with
      patients who left treatment earlier. Patients who remained in treatment were also
      more likely to be attending self-help meetings, continuing in outpatient
      treatment, or attending school. However, for the 447 patients randomly assigned
      to the three conditions, there were no significant differences between treatment
      modalities on any of the variables at nine-month follow-up. The new intensive
      treatment program was not shown to be superior to more traditional treatment
      programs.

PMID- 9634158
TI  - Prevalence of physical illness among psychiatric inpatients who die of natural
      causes.
AB  - OBJECTIVE: The state psychiatric hospital is experiencing an increase in
      medically sick and aging patients who die of natural causes while hospitalized.
      This study explored the "medicalization" of the state hospital by examining the
      prevalence of medical illness and its relationship with psychiatric illness and
      age among state hospital psychiatric inpatients who died of natural causes-
      deaths that were not accidents, homicides, or suicides. METHODS: A total of 179
      inpatients who died of natural causes at Western State Hospital in Washington
      State between 1989 and 1994 were studied retrospectively through case file
      review. Their demographic and institutional characteristics and psychiatric
      diagnoses were compared with those of others treated at the hospital (N=9,258).
      The medical diagnoses of patients who died were analyzed by age and psychiatric
      condition. RESULTS: The patients who died were much older than the other patients
      treated during the study period. Two-thirds of those who died had organic mental
      disorders, mostly dementia, whereas only a fifth of the other patients had these
      disorders. The patients who died had a mean of eight physical illnesses, with a
      range from none to 21. Circulatory and respiratory conditions were most
      prevalent, affecting half to two-thirds of patients; these conditions had high
      rates of comorbidity with organic mental disorders. CONCLUSIONS: The
      characteristics of the state hospital population and the services provided are
      shifting in response to mental health reform and new policies on patient self
      determination. Increased emphasis on medical care added to traditional
      psychiatric services will require increased financial and personnel resources.

PMID- 9634159
TI  - Assessing the quality of psychiatric hospital care: a German approach.
AB  - OBJECTIVE: The German Ministry of Health commissioned a nonprofit organization to
      develop a tool for assessing the quality of psychiatric hospital care. METHODS:
      The authors were members of an expert group established to develop an assessment
      tool that could be used by professional caregivers, patients, patients'
      relatives, managers, purchasers, and mental health care planners. RESULTS: A
      three-dimensional model was developed in which 23 quality standards may be
      applied to 28 areas of practice. For each application, questions can be asked at
      four levels to stimulate ongoing quality management: the individual treatment
      process, the individual outcome, the treatment unit, and the hospital as a whole.
      The authors provide sample questions to illustrate the approach. CONCLUSIONS: The
      approach to quality assessment embodied in the model is comprehensive and
      addresses ethical issues, but it is also complicated and difficult to handle.
      Unlike models developed in the United States, it is not intended to be objective
      or standardized, and it does not yield a score. To some extent, the model's
      approach to assessment may reflect German cultural values and traditions.

PMID- 9634160
TI  - The effects of animal-assisted therapy on anxiety ratings of hospitalized
      psychiatric patients.
AB  - OBJECTIVE: Animal-assisted therapy involves interaction between patients and a
      trained animal, along with its human owner or handler, with the aim of
      facilitating patients' progress toward therapeutic goals. This study examined
      whether a session of animal-assisted therapy reduced the anxiety levels of
      hospitalized psychiatric patients and whether any differences in reductions in
      anxiety were associated with patients' diagnoses. METHODS: Study subjects were
      230 patients referred for therapeutic recreation sessions. A pre- and
      posttreatment crossover study design was used to compare the effects of a single
      animal-assisted therapy session with those of a single regularly scheduled
      therapeutic recreation session. Before and after participating in the two types
      of sessions, subjects completed the state scale of the State-Trait Anxiety
      Inventory, a self-report measure of anxiety currently felt. A mixed-models
      repeated-measures analysis was used to test differences in scores from before and
      after the two types of sessions. RESULTS: Statistically significant reductions in
      anxiety scores were found after the animal-assisted therapy session for patients
      with psychotic disorders, mood disorders, and other disorders, and after the
      therapeutic recreation session for patients with mood disorders. No statistically
      significant differences in reduction of anxiety were found between the two types
      of sessions. CONCLUSIONS: Animal-assisted therapy was associated with reduced
      state anxiety levels for hospitalized patients with a variety of psychiatric
      diagnoses, while a routine therapeutic recreation session was associated with
      reduced levels only for patients with mood disorders.

PMID- 9634161
TI  - Outcome for people with schizophrenia before and after Medicaid capitation at a
      community agency in Colorado.
AB  - OBJECTIVE: To investigate the effect of a capitated funding mechanism for the
      psychiatric care of Medicaid recipients, a study of outcome, satisfaction, and
      service utilization among adults with schizophrenia and schizoaffective disorder
      was conducted at a Colorado agency before and after the introduction of the new
      funding mechanism. METHODS: Two random samples of 100 clients each were selected,
      one a year before capitation was introduced and one a year after. Subjects were
      interviewed about their quality of life, needs, and service satisfaction.
      Psychopathology and service utilization were also measured. RESULTS:
      Psychopathology was lower after capitation in most dimensions. The number of
      subjects admitted to the hospital during a six-month period beginning a year
      after capitation was 57 percent lower than in the equivalent period before
      capitation, with no increase in the amount of outpatient treatment provided.
      Subjects reported improved quality of life in the domains of work, finances, and
      social relations. Significant changes in needs or service satisfaction were not
      detected. CONCLUSIONS: No evidence was found that Medicaid capitation had an
      adverse effect on the client population after one year. Findings suggested that
      capitation led to an efficient use of treatment resources.

PMID- 9634162
TI  - Cost-effectiveness of television, radio, and print media programs for public
      mental health education.
AB  - Mass media campaigns to influence public attitudes and behaviors in the area of
      mental health must consider cost-effectiveness, which is based on actual costs,
      the number of people reached (exposures), and the impact of the program on the
      individual. Cost per exposure is a critical factor. The authors review their
      experience in developing media programs in several broadcast formats and in
      print. Their experience suggests that an effective television production has a
      very high per-exposure cost and that radio is a more cost-effective way to
      present health messages. Radio programs also have the advantage of reaching
      people in their homes or cars or at work. Brief segments may be particularly cost
      effective because they can be can be inserted between programs during prime-time
      hours. Print media--newspapers, magazines, and newsletters--can be cost-effective
      if magazine or newspaper space is free, but newsletters can be costly due to
      fixed postage costs. One advantage of print is that it can be reread, clipped
      out, copied, and passed on.

PMID- 9634163
TI  - Treatment of inhalant-induced psychotic disorder with carbamazepine versus
      haloperidol.
AB  - OBJECTIVE: The efficacy and adverse effects of carbamazepine and haloperidol were
      compared in the treatment of inhalant-induced psychotic disorder. METHODS: Forty
      male patients admitted to an acute psychiatric unit for treatment of inhalant
      dependence and inhalant-induced organic mental disorder, as diagnosed by DSM-III
      R, were randomly assigned to receive five weeks of treatment with carbamazepine
      or haloperidol in identical-appearing capsules. The Brief Psychiatric Rating
      Scale and the DiMascio Extrapyramidal Symptoms Scale were administered weekly.
      RESULTS: Both treatment groups improved significantly over time. A reduction of
      symptom severity of 48.3 percent in the carbamazepine group and 52.7 percent in
      the haloperidol group was observed. Approximately half the patients in each group
      were considered treatment responders at the end of the study. Adverse effects
      were significantly more common and more severe in the haloperidol group.
      CONCLUSIONS: Carbamazepine appears to have comparable efficacy but fewer adverse
      effects than haloperidol for the treatment of inhalant-induced psychotic
      disorder.

PMID- 9634164
TI  - Content and curriculum in psychoeducation groups for families of persons with
      severe mental illness.
AB  - OBJECTIVE: The study compared problems identified by participants in a workshop
      for families with a relative who had severe mental illness with topics addressed
      in published descriptions of multifamily psychoeducational interventions to
      determine whether the problems and needs of family members differed from those
      covered in professionally prepared psychoeducational materials. METHODS:
      Participants in a one-day psychoeducational workshop were asked to identify and
      rank in order of importance the problems they faced in managing mental illness.
      Most workshop participants were family members who did not have a severe mental
      illness, but family members with a severe mental illness and mental health
      service providers also attended. Lists of problems generated by 86 participants
      containing a total of 355 items were analyzed for content, and 11 problem
      categories were identified and ranked. These categories were then compared with
      the content of multifamily psychoeducation programs described in the literature.
      RESULTS: Although the methodology limited generalizability of findings, the
      results suggest important distinctions between content developed by professionals
      and the needs identified by family members, particularly in families' greater
      emphasis on negative symptoms and on family relationships. CONCLUSIONS: The
      findings suggest that input from the family, the ill family member, and mental
      health providers is necessary for developing psychoeducation curricula that will
      meet families' needs. Professionals who design multifamily psychoeducation
      curricula are encouraged to incorporate enough flexibility to accommodate the
      specific needs of members of particular groups and to provide general information
      that is useful for all groups.

PMID- 9634165
TI  - HIV-related risk behaviors among psychiatric inpatients in India.
AB  - The study explored patterns of risk behavior and knowledge about HIV and AIDS
      among patients in an inpatient psychiatric facility in south India. Fifty-nine
      consecutive patients admitted to a state psychiatric hospital were interviewed
      using a semistructured questionnaire. Fifty-one percent had a history of recent
      risk behavior, and 86 percent had inadequate knowledge about AIDS. The most
      common high-risk behavior was unprotected heterosexual intercourse with a high
      risk partner. There was no correlation between knowledge and high-risk behavior.
      The findings underscore the need to specifically tailor intervention programs.

PMID- 9634166
TI  - A comparison of psychotic and nonpsychotic substance users in the psychiatric
      emergency room.
AB  - Current illicit drug and alcohol users were identified by laboratory evaluation
      of urine samples from nonpsychotic patients without a primary clinical diagnosis
      of a substance use disorder seen in a psychiatric emergency room. Urine screens
      revealed that 32 of 93 nonpsychotic patients (34 percent) had used a substance
      just before visiting the emergency room. Compared with nonusers, users were more
      often Caucasian females with adjustment disorders who admitted their previous
      substance use. The prevalence of concurrent use among nonpsychotic patients was
      higher than among psychotic patients. Nonpsychotic and psychotic users differed
      in gender, marital status, level of suicidality, self-report of use, the
      clinician's suspicion of use, use of seclusion during the visit, admitting
      status, level of care, and disposition.

PMID- 9634167
TI  - Cost-effectiveness of clozapine therapy for severe psychosis.
AB  - The cost-effectiveness of using the atypical antipsychotic medication clozapine
      for severe psychosis was examined in a rural public-sector community mental
      health setting in Virginia. Based on a sample of 20 patients, use of clozapine
      resulted in estimated cost savings of between $3,000 and $9,000 per patient per
      year, including the costs of dropouts from treatment. Savings were mainly due to
      a decline in hospitalization from 47.7+/-59.8 days per patient in the year before
      clozapine treatment to 4.6+/-11.3 days in the year after. Although this study had
      methodological limitations, the results suggest that clozapine may be cost
      effective in this setting.

PMID- 9634168
TI  - Outcomes of ultrarapid opiate detoxification combined with naltrexone maintenance
      and counseling.
AB  - Combining naltrexone and clonidine under general anesthesia is being used to
      shorten opiate detoxification. This study determined the one-year relapse rate of
      persons detoxified using this ultrarapid method in conjunction with naltrexone
      maintenance and counseling. Structured telephone interviews were held with 83 out
      of a random sample of 113 male patients who were detoxified via the ultrarapid
      method more than one year before the interview (average 1.5 years) and their
      significant others. Relapse was defined as at least two weeks of daily opiate
      use. According to patients and significant others, 57 percent of patients had not
      relapsed. This rate is better than rates obtained in studies of other
      detoxification methods.

PMID- 9634169
TI  - Efficacy vs. effectiveness in psychiatric research.

PMID- 9634170
TI  - Dealing with illiteracy.

PMID- 9634171
TI  - Interindividual variability in body composition and resting oxygen consumption
      rate in breeding tree swallows, Tachycineta bicolor.
AB  - Basal metabolic rate is one of the most widely measured physiological traits.
      Previous studies on lab mice and field-caught lizards suggest that individuals
      with relatively high basal metabolic rates or standard metabolic rates have
      relatively large masses of metabolically active tissues (e.g., heart, kidney,
      liver). As these are energetically expensive organs, there may be variability
      between breeding seasons dependent on, for example, availability of prey and
      capacity for energy intake. We present data from breeding tree swallows
      (Tachycineta bicolor) collected over two successive seasons. There was no
      difference between years in resting oxygen consumption rates, although there were
      significant interannual differences in the masses of all organs and tissues
      except the pectoralis. Interindividual differences in the masses of the kidney
      and small intestine explained 21% of the variation in oxygen consumption rates.
      Although individuals with relatively high resting oxygen consumption rates had
      relatively large, metabolically active kidneys, they had relatively small
      intestines and pectoral muscles. This is in contrast to all previous studies on
      mammals and to the single interspecific study of birds. Oxygen consumption rate
      also correlated positively with hematocrit. Our results suggest that assumptions
      of consistent positive relationships between resting oxygen consumption rate and
      organ masses cannot be extended intraspecifically for birds.

PMID- 9634172
TI  - Behavior and muscle performance in heterothermic bats.
AB  - Body temperatures of winter-resident Korean bats typically range from 10 degrees
      to 40 degrees C between August and September and from 3 degrees to 15 degrees C
      between January and April. To learn how behavior and the motor systems of
      heterothermic bats respond to this body-temperature variation, we examined whole
      organism performance and the temperature-dependence of contractile properties of
      flight muscle in Murina leucogaster ognevi. In winter and midspring, the lowest
      limits of body temperature were 8 degrees C for biting and crawling, 16 degrees C
      for visually observable shivering, 22 degrees C for wing flapping (without
      powered flight), and 28 degrees C for aerial flight. In summer, the lowest
      temperature limits changed little for biting and wing flapping, but the
      temperature limits increased about 3 degrees C for crawling, shivering, and
      flight. Maximum isometric tetanic tension of the isolated biceps brachii muscle
      was almost insensitive to tissue temperatures between 10 degrees and 40 degrees
      C, with an average temperature coefficient of 1.02 in summer and of 0.96 in
      winter. Rate of tetanic tension production between 10 degrees and 40 degrees C
      and shortening velocity and power between 15 degrees and 25 degrees C were
      temperature sensitive, with average temperature coefficients of 1.3-2.3. Seasonal
      differences in contractile properties within each temperature were not
      significant, except for maximum tetanic tension at 30 degrees - 40 degrees C.
      Thus, the motor system of the bats had functional capacity over the range of body
      temperature experienced in winter to summer. The temperature-dependence of
      behavior was consistent with muscle physiology. The defensive behaviors, like
      biting and crawling, observed at 8 degrees - 12 degrees C body temperature could
      be exerted by using temperature-independent tetanic tension, whereas activities,
      such as flight, that require power generation would be restricted to higher body
      temperatures by temperature-sensitive rate properties. Some rate processes
      appeared to be more temperature sensitive in summer than in winter.

PMID- 9634173
TI  - The effects of environmental temperature, hypoxia, and hypercapnia on the
      breathing pattern of saltwater crocodiles (Crocodylus porosus).
AB  - This study aimed to describe the effects of change in environmental temperature,
      hypoxia, and hypercapnia on the breathing pattern of Crocodylus porosus.
      Increased environmental temperature, hypoxia, and hypercapnia each caused an
      increase in minute ventilation and changes in breathing pattern. Breathing
      frequency increased and the duration of the nonventilatory period decreased in
      response to all three conditions. Under hypercapnia tidal volume also increased,
      with no change in rate of inspiration. The number of breaths per breathing burst
      decreased with increased temperature but remained unaltered under hypoxia.
      Hypercapnia reduced the number of breaths per burst at 20 degrees C, but the
      number did not decrease further at 30 degrees C. The results support the idea
      that the responses to increased temperature, hypoxia, and hypercapnia are under
      separate control but that some effects of hypercapnia and temperature may involve
      a common regulatory pathway.

PMID- 9634174
TI  - Performance limits of low-temperature, continuous locomotion are exceeded when
      locomotion is intermittent in the ghost crab.
AB  - Since a decline in temperature decreases aerobic capacity and slows the kinetics
      of exercise-to-rest transitions in ectotherms, we manipulated body temperature to
      better understand the performance limits of intermittent locomotion. Distance
      capacity (i.e., the total distance traveled before fatigue) of the ghost crab,
      Ocypode quadrata, was determined during acute exposure to 15 degrees C inside a
      treadmill-respirometer. Instead of exacerbating the near-paralyzing effects of
      low body temperature resulting from the frequent transitions, intermittent
      locomotion allowed animals to exceed the performance limits measured during
      steady-state locomotion. At low temperature, distance capacity for continuous
      locomotion at 0.04 m s(-1) (83% maximum aerobic speed) was 60 m. When 30 s of
      exercise at 0.08 m s(-1) (166% maximum aerobic speed) was alternated with 30 s of
      rest, distance capacity increased to 271 m, 4.5-fold greater than continuous
      locomotion at the same average speed (83% maximum aerobic speed). A 30-s pause
      following a 30-s exercise period was sufficient for maintaining low lactate
      concentrations in muscle and for partial resynthesis of arginine phosphate. A
      greater dependency on nonoxidative metabolism due to slowed oxygen uptake
      kinetics at low temperature resulted in a decreased duration of the critical
      exercise period, which increased performance relative to that measured at higher
      temperatures (30 s at 15 degrees C vs. 120 s at 24 degrees C). Despite the ghost
      crab's limited aerobic capacity at 15 degrees C, distance capacity during
      intermittent locomotion at low temperature can be comparable to that of a crab
      moving continuously at a body temperature 10 degrees C warmer. While endurance
      capacity is generally correlated with maximum aerobic speed, we have demonstrated
      that both locomotor behavior and body temperature must be considered when
      characterizing performance limits.

PMID- 9634175
TI  - Glucose, lactate, and beta-hydroxybutyrate utilization by rainbow trout brain:
      changes during food deprivation.
AB  - In order to evaluate the normal (fed conditions) substrate utilization rates of
      rainbow trout (Oncorhynchus mykiss) brain, CO2 production from glucose, lactate,
      and beta-hydroxybutyrate was tested in pooled brains. Oxidation rates, as well as
      the capacity for metabolism of carbohydrate and ketone bodies, were also
      evaluated in brain of rainbow trout that were food-deprived for 14 d. Under
      normal (fed) conditions, rainbow trout brain oxidized glucose and lactate at
      rates higher than those described for mammals; oxidation rates of beta
      hydroxybutyrate were lower in rainbow trout brain than those observed for lactate
      and glucose, and also lower than those described for mammals. Under food
      deprivation conditions, glucose and lactate oxidation rates decreased in brains,
      suggesting the existence of brain metabolic depression, and beta-hydroxybutyrate
      oxidation rates sharply increased, suggesting increased utilization of ketone
      bodies.

PMID- 9634176
TI  - Carbon release from purified chemoautotrophic bacterial symbionts of the
      hydrothermal vent tubeworm Riftia pachyptila.
AB  - The gutless hydrothermal tubeworm Riftia pachyptila Jones relies mainly on its
      chemoautotrophic bacterial symbionts to supply nutrients in the form of secreted
      organic compounds resulting from fixation and incorporation of CO2. In this
      study, symbionts were purified, tested for viability, and incubated in the
      presence of labeled CO2. We demonstrated that purified symbionts can be used as a
      viable alternative to experiments with bacterial cultures. Several organic acids,
      sugars, and amino acids were labeled, but their fraction of the total label
      stayed generally constant during the incubation times used. However, increasing
      fractions of succinate and, to a lesser degree, glutamate were excreted into the
      incubation medium, indicating that these are probably the main carbon-containing
      compounds transferred from the symbionts to the host. Glutamate could also
      account for the transport of nitrogen from the symbionts to the host.

PMID- 9634177
TI  - Daily and seasonal rhythms in selected body temperatures in the Australian lizard
      Tiliqua rugosa (Scincidae): field and laboratory observations.
AB  - This study examined daily and seasonal activity and thermoregulatory behaviour of
      the sleepy lizard, Tiliqua rugosa, a large, diurnally active temperate-dwelling
      Australian lizard, in the field and laboratory. Activity temperatures in the
      field were compared with those selected by lizards in laboratory thermal
      gradients in order to assess the extent to which endogenous versus exogenous
      factors contribute to seasonal variations in thermoregulatory behaviour. In the
      field, lizards are most active in late winter-spring (August-November), during
      which their activity varies from mostly unimodal on days of mild temperature to
      bimodal on hot days. In late spring-summer (November-January), activity is
      largely restricted to early morning, and at all other seasons sleepy lizards are
      rarely active. The winter-spring activity of sleepy lizards is constrained by low
      environmental temperatures, as lizards at these seasons have low body
      temperatures in the field but higher temperatures in laboratory thermal
      gradients. The lower temperatures selected in the laboratory in the summer-autumn
      months suggest the avoidance of high ambient temperatures and general inactivity
      in the field at these times. Thermal selection in the laboratory at the eight
      times of year tested showed that the phase of the minimum and maximum temperature
      selected and the amplitude of the rhythm of temperature selected varied
      continuously with the time of year. These daily and seasonal shifts in
      thermoregulatory behaviour may be regulated by endogenous physiological
      mechanisms coupled with seasonal ecological constraints such as food
      availability.

PMID- 9634178
TI  - Limits to milk flow and energy allocation during lactation of the hispid cotton
      rat (Sigmodon hispidus).
AB  - Energy allocation for maternal maintenance and milk production was examined in
      lactating hispid cotton rats (Sigmodon hispidus) supporting three to seven
      offspring at 10 degrees or 24 degrees C. Lactating mothers obtained most of their
      energy from dietary intake (ca. 90%), and the remainder was withdrawn from
      maternal stores. There was no indication that a central limit to maternal energy
      assimilation constrained lactational performance. Maternal energy assimilation
      increased with a larger litter size (a higher production cost) and a decline in
      ambient temperature (a higher thermoregulatory cost) during lactation, without
      reaching an apparent limit. Further, there was no evidence of competitive energy
      allocation, which might occur if maternal energy assimilation were limited.
      Hence, increases in maternal thermoregulatory expenditure during lactation did
      not decrease the energy allocation for milk production. Lactating mothers had a
      capacity to increase milk production. Nonetheless, the milk flow did not fully
      satisfy the energy requirements of dependent offspring in larger litters or at
      the lower ambient temperature (growth rates of offspring declined in both cases).
      Local physiological constraints and behavioral effects appear to limit maternal
      allocation during lactation. Constraints to allocation may be favored by
      selection because they reduce maternal risk or reproductive cost.

PMID- 9634179
TI  - Effects of ambient temperature, diet quality, and food restriction on body
      composition dynamics of the prairie vole, Microtus ochrogaster.
AB  - We manipulated diet quality, food availability, and ambient temperature to
      investigate the role of these variables in fat deposition by growing prairie
      voles (Microtus ochrogaster) and fat use by adult voles. Exposure to either 5
      degrees C or a high-fiber diet reduced fat deposition by growing voles and also
      reduced growth as measured by body length. Adult voles on the high-fiber diet
      reduced fat content, but exposure to 5 degrees C had no effect on body
      composition. Both the high-fiber diet and exposure to 5 degrees C caused
      increased food intake and reduced diet digestibility for adult voles. Restricting
      access to food resulted in reduced lipid mass of all adult voles and reduced fat
      free mass of those held at 5 degrees C. When faced with poor food quality or cold
      ambient temperature, voles will increase food intake rather than catabolize lipid
      tissue. When food availability is limited, however, voles will use fat stores to
      meet the balance of their energy requirements.

PMID- 9634180
TI  - Estimation of total body water in pinnipeds using hydrogen-isotope dilution.

PMID- 9634181
TI  - Low-field magnetic resonance imaging of early subchondral cyst-like lesions in
      induced cranial cruciate ligament deficient dogs.
AB  - Six healthy adult male mongrel dogs underwent cranial cruciate ligament
      transection in the left stifle. Survey radiography of both stifles and low-field
      (0.064 T) MRI of the left stifle were performed preoperatively and at 2, 6, and
      12 weeks postoperatively. Focal changes in signal intensity were seen with MRI in
      the subchondral bone of the medial tibial condyle at 2 and 6 weeks
      postoperatively. At 12 weeks postoperative, a cyst-like lesion was detected using
      MRI in the subchondral bone of the medial tibial condyle in 4 of 6 dogs and a
      less defined lesion at this site in the remaining 2 dogs. The cyst-like lesion
      was spherical in shape and showed typical characteristics of fluid with low
      signal intensity on T1-weighted images, high signal intensity on T2-weighted
      images and high signal intensity on inversion recovery images. The lesion was
      seen in the subchondral bone of the caudal medial and/or middle region of the
      tibial plateau slightly cranial to the insertion of the caudal cruciate ligament.
      No subchondral cysts were seen in the tibia on radiographs. Histopathologically,
      the tibia was characterized by a loose myxomatous phase of early subchondral cyst
      formation.

PMID- 9634182
TI  - Contrast radiography of the lower urinary tract in the management of obstructive
      urolithiasis in small ruminants and swine.
AB  - Contrast radiographic visualization of the small ruminant and porcine lower
      urinary tract is an infrequently used modality for the evaluation and management
      of obstructive urolithiasis. The administration of contrast medium through a tube
      cystostomy catheter used to divert urine flow until the resolution of the
      obstruction may provide an easy method to evaluate the status of the urethral
      obstruction. Contrast fluoroscopy is utilized to monitor and visualize
      therapeutic flushing of the urethra. A review of 26 patients seen at the
      Veterinary Medical Teaching Hospital suggested that among the radiographic
      techniques used, positive contrast normograde cystourethrography through the tube
      cystostomy catheter allowed the best visualization of the lower urinary tract
      structures and enabled assessment of the resolution of the obstructive lesion.

PMID- 9634183
TI  - Radiographic diagnosis--granulomatous pneumonia with intralesional acid-fast
      bacilli in an Amazon parrot (Amazona aestiva).

PMID- 9634184
TI  - Developmental change of lateral ventricular volume and ratio in Beagle-type dogs
      up to 7 months of age.
AB  - Eighteen healthy Beagle-type dogs were studied using magnetic resonance (MR)
      imaging from a few days after birth up to 7 months of age. We evaluated the onset
      of lateral ventricular expansion, the developmental change of lateral ventricular
      volume and the ratio of the largest to the smallest lateral ventricular volume.
      The onset of lateral ventricular expansion was defined as the day that the
      expansion by cerebrospinal fluid (CSF) was first visible in unilateral or
      bilateral lateral ventricles on the transverse images at the level of the
      intraventricular foramen. It was found that the expansion of lateral ventricles
      were first detectable at 3-4 weeks. Lateral ventricular volume ratio varied most
      from the onset of lateral ventricular expansion to 75 days of age and stabilized
      after that, although absolute brain and lateral ventricular volumes continued to
      increase.

PMID- 9634185
TI  - Radiographic diagnosis--gastroesophageal intussusception in a cat.

PMID- 9634186
TI  - Hydrothorax secondary to a perinephric pseudocyst in a cat.
AB  - Hydrothorax was identified in a 14-year-old Siamese cat with a pre-existent
      perinephric pseudocyst. The pleural fluid was classified as a low-protein
      transudate. Intrapseudocystic scintigraphy confirmed a direct communication
      between the pseudocyst and the pleural space. The hydrothorax resolved following
      pseudocystectomy and unilateral nephrectomy, demonstrating that the pseudocyst
      caused the hydrothorax.

PMID- 9634187
TI  - Transesophageal ultrasonography of the normal canine mediastinum.
AB  - The mediastinum of eight normal research dogs was examined by transesophageal
      ultrasonography with a 5 MHz frequency transducer to establish a baseline for
      future use of this new imaging modality as a diagnostic tool. Each examination
      consisted of 360 degree scans in both transverse and sagittal planes from the
      thoracic inlet to the esophageal hiatus. Dissections of four of these research
      dogs were then performed to confirm transesophageal ultrasonography findings.
      Transesophageal ultrasonography of the mediastinum was a good imaging modality
      for the evaluation of the heartbase, the major cranial mediastinal vessels, the
      descending aorta, and occasionally part of the azygos vein. Anatomic orientation
      was best obtained by beginning the examination at the heart base. Lymph nodes and
      smaller caliber vessels could not be distinguished from surrounding tissues;
      however, Doppler ultrasound was useful for identifying the smaller vessels.
      Although a 5 MHz frequency transducer is preferred for transesophageal
      echocardiography, a higher frequency transducer would improve the resolution of
      the images of small near-field structures and may be more appropriate for
      mediastinal imaging.

PMID- 9634188
TI  - Prevalence of gallbladder sludge in dogs as assessed by ultrasonography.
AB  - Ultrasonography of the gallbladder was performed in 3 groups of dogs: 30
      clinically healthy dogs, 50 dogs with hepatobiliary disease, and 50 dogs with
      diseases other than hepatobiliary disease. The gallbladder was evaluated for the
      presence of sludge (echogenic material without acoustic shadowing). Maximal
      gallbladder length, width, height, and area were measured as well as the
      gallbladder wall thickness. The relative sludge area was calculated as the ratio
      of sludge area over gallbladder area on longitudinal images. No significant
      difference was found in the prevalence of gallbladder sludge among healthy dogs
      (53%), dogs with hepatobiliary diseases (62%), and dogs with other diseases
      (48%). The mean age of dogs with sludge was higher than the mean age of dogs
      without sludge in dogs with hepatobiliary disease and dogs with other diseases (p
      < 0.05). The mean relative sludge area did not differ significantly among the 3
      groups. A trend to larger gallbladder dimensions in dogs with sludge compared to
      dogs without sludge was detected within the 3 groups. The gallbladder wall
      thickness was not different between dogs with and without sludge within the 3
      groups. However, the gallbladder wall was more frequently isoechoic than
      hyperechoic to the liver in dogs with sludge than in dogs without sludge. The
      results of this study indicate that gallbladder sludge, in dogs, is not
      particularly associated with hepatobiliary disease and should be considered an
      incidental finding.

PMID- 9634189
TI  - Ultrasonographic evaluation of the prostate in healthy intact dogs.
AB  - Sagittal and transverse ultrasonographic images of the prostate gland were
      obtained in 100 healthy adult intact male dogs. Prostatic length, width, and
      height on transverse and sagittal images as well as the presence of prostatic
      cysts were determined. Linear regression and correlation analysis were performed
      between prostatic parameters (length, width, height on sagittal and transverse
      images, and estimated volume) and parameters related to body size (body weight,
      body height, left kidney length and aortic diameter) and age of the dogs.
      Significant positive correlations were found between all prostatic parameters and
      parameters related to body size and age. Maximum predicted values for prostatic
      parameters for a given body weight and age were determined based on the upper
      limit of the 95% confidence interval of the mean predicted values. Such values
      should represent a useful tool for ultrasonographic evaluation of the prostate in
      the dog. Prostatic cysts were found in 14% of the dogs.

PMID- 9634190
TI  - Ultrasonographic findings in 14 dogs with ectopic ureter.
AB  - To evaluate ultrasonography as an alternative to contrast radiography for
      diagnosis of ectopic ureter in dogs, ultrasonography of the urinary tract was
      performed prospectively in a series of urinary incontinent dogs anesthetized for
      contrast radiography. Fourteen dogs had ectopic ureter based on surgical,
      necropsy or unequivocal contrast radiographic findings. There were eight females
      and six males of a variety of breeds; five were Labrador retrievers. Mean (range)
      age at the time of diagnosis was 1.2 (0.2-4) years for females and 3.5 (0.3-5)
      for males (p < 0.05). Ectopic ureters were unilateral in five dogs (2 left; 3
      right) and bilateral in nine dogs. Both ultrasound images and contrast
      radiographs were positive for 21 (91%) ectopic ureters; the same two ectopic
      ureters were not detected using either modality. The termination of each of the
      five normal ureters was visible on ultrasound images; two (40%) were visible on
      radiographs. Other ultrasonographic findings included dilatation of the ectopic
      ureter and/or ipsilateral renal pelvis in ten (43%) instances, evidence of
      pyelonephritis in two dogs (with enlargement of the contralateral kidney in one
      dog), and urethral diverticuli in one dog. Ultrasonography is a practical
      diagnostic test for ectopic ureter in dogs. In this series there was close
      correlation between the ultrasonographic and contrast radiographic findings for
      each ectopic ureter, but ultrasonography enabled more accurate determination of
      normal ureteral anatomy.

PMID- 9634191
TI  - Ultrasound corner--attenuation: the clinical utility of subjective sonographic
      assessment.

PMID- 9634192
TI  - Ultrasonographic appearance of ovarian tumors in 10 dogs.
AB  - Signalment, clinical history, physical examination, clinicopathologic,
      radiographic and ultrasonographic findings of 10 female dogs with histologically
      confirmed ovarian neoplasms were reviewed. Ultrasonographic images and reports
      were reviewed for (1) location, size, outer margins, and echogenicity of the
      mass(es), (2) presence of free abdominal fluid, (3) evidence of uterine
      abnormalities, and (4) signs of metastatic disease. The masses were classified
      according to their ultrasonographic pattern in solid, solid with cystic
      component, and cystic. The masses were ultrasonographically reported as being of
      ovarian origin in eight dogs, and this origin was included in the list of
      differentials in the remaining two dogs. When present, abdominal effusions and
      uterine abnormalities were diagnosed by means of ultrasound.

PMID- 9634193
TI  - Detection of portal blood flow using per-rectal 99mTc-pertechnetate scintigraphy
      in normal cats.
AB  - This study reports data obtained from per-rectal 99mTc-pertechnetate portal
      scintigraphy in normal cats. It examines the effects of chemical restraint and
      the methods employed in defining regions of interest (ROIs) on the shunt index
      derived from this data. Six normal cats were used for the study; all six were
      chemically restrained for imaging using propofol and later four of them were
      manually restrained for comparison. Portal blood flow was studied and the mean
      shunt index was found to be 5.9% +/- 3.9 when ROIs were operator defined and 9.2%
      +/- 4.4 when ROIs were defined using an isocontour program. In cats that were
      restrained using propofol and operator defined ROIs, the mean value for the time
      between detection of radioactivity in the liver and in the heart was 14 +/- 1
      seconds.

PMID- 9634194
TI  - Effect of advanced glycosylation end products on the activity of integrins
      expressed on U937 cells.
AB  - Advanced glycosylation end products (AGEs) are formed both in healthy old persons
      and diabetic patients by nonenzymatic glycosylation. However, AGEs are supposed
      to be a major factor in the vascular damages associated with diabetes. The aim of
      this study was to assess the effect of AGEs on the activity of cell adhesion
      molecules expressed on lymphoid cells. Human serum albumin (HSA) was glycosylated
      in vitro and used as a specific stimulating agent with U937 cells. The effect of
      glc-HSA was evaluated by the method of homotypic adhesion and adhesion to
      immunoplate coated with fibronectin. Specific monoclonal antibodies against
      integrins and ICAM-1 were applied in these studies. It was shown that glc-HSA
      enhanced the homotypic adhesion. The latter was mediaced via beta2-integrins as
      the effect was recorded after 15 min. incubation. The homotypic adhesion for the
      cells treated with glc-HSA followed the same kinetics as the cells incubated with
      phorbol myriastate acetate, which was used as a positive control. An anti-CD18
      antibody inhibited the adhesion of U937 cells which indicated that the glc-HSA
      had a positive effect on the activity of beta2-integrins. Treatment with glc-HSA
      did not interfere with the adhesion of the referent cells to fibronectin coated
      plate. Based on these results the conclusion was drawn that the advanced
      glycosylation end products have a differential effect on the activity of integrin
      subfamilies expressed on cells of monocyte-macrophage origin.

PMID- 9634195
TI  - Activated human T-cells bestow T-cell antigens to non-T-cells by intercellular
      antigen transfer.
AB  - The mechanism of the appearance of T-cell antigens on B-cells, following in vitro
      activation of peripheral blood lymphocytes, was analyzed using the following
      model: Purified T-cell suspensions were activated by exposure to
      phytohemagglutinin (PHA) for 3 days, and then incubated for one hour in the
      presence of cells of either Raji or K562 cells. The expression of T-cell antigens
      on the cell lines was determined using immunofluorescent F(ab)2 fragments of
      monoclonal antibodies (mAbs). Following exposure of the CD19+ Raji cells to
      activated T lymphocytes, 87.6% of the CD19+ cells coexpressed CD2. A large
      proportion of the CD19+ cells also expressed CD4, CD5, and CD8 antigens. Similar
      results were obtained with Raji cells that were prelabeled with calcein AM. In
      Raji cells, which were rendered CD5+ following incubation with activated T cells,
      only a negligible level of CD5 mRNA was detected with a sensitive RT-PCR
      technique, probably attributable to contamination with T cells. K562 cells
      incubated with activated T cells acquired CD2 but not the CD4 and CD8 antigens.
      Exposure of either Raji or K562 cells to mAb against CD58 inhibited the transfer
      of CD2. The present study indicates that following their activation, T-cells gain
      the capacity to transfer T-cell antigens to non-T cells and that CD2 and CD58
      molecules are involved in this process.

PMID- 9634196
TI  - Efficient induction of human CD4+ T cell lines reactive with a self-K-ras-derived
      peptide in vitro, using a mAb to CD29.
AB  - In recent studies, we analyzed effects of a large series of mAbs submitted to T
      cell and adhesion structure sections of 6th International Workshop on Human
      Leukocyte Differentiation Antigens, on proliferative responses of a human CD4+ T
      cell clone. We found that certain mAbs to CD27, CD28, CD29, CD43 and CD44
      markedly restore T cell responsiveness, only in the presence of the natural
      peptide ligand at low concentrations and even in the absence IL-2. To set up
      efficient strategies for developing T cell lines and clones reactive with self
      peptides in vitro, we stimulated PBMC with a K-ras-derived peptide in the
      presence of these mAbs and found that: (a) anti-CD29 mAb MAR4 is effective for in
      vitro expansion of K-ras (residue 3-20)-reactive T cells from PBMC; (b) indeed,
      DR8 (DRB*0802)-restricted and DR51 (DRB5*0102)-restricted CD4+ T cell clones were
      established from the T cell lines; (c) MAR4 inhibits anti-CD3-induced apoptosis
      of PBMC; and (d) MAR4 is effective in enhancing anti-CD3- and antigen-induced
      proliferative responses of PBMC. Therefore, mAb MAR4 increased efficiency in
      establishing T cell clones from PBMC, both by suppressing antigen-driven
      activation-induced cell death and by enhancing the T cell proliferation, only in
      the presence of TCR/CD3-mediated stimulation. Possible application of MAR4 for
      establishing self-reactive T cell lines and expanding T cells ex vivo for anti
      cancer immunotherapy, is discussed.

PMID- 9634197
TI  - The regulation of phenotype and function of human liver CD3+/CD56+ lymphocytes,
      and cells that also co-express CD8 by IL-2, IL-12 and anti-CD3 monoclonal
      antibody.
AB  - The regulation of phenotype and function of human liver infiltrating lymphocytes
      (LIL) by in vitro culture with IL-2, IL-12 and anti-CD3 monoclonal antibodies
      (mAb) was investigated. The CD3+ LIL which express 50% less CD3 molecules per
      cell than peripheral blood T lymphocytes, exhibited a 6-fold reduction in
      proliferation when stimulated through the CD3 complex by anti-CD3 mAb. LIL
      freshly isolated or cultured in medium did not suppress MLR response, nor were
      they cytotoxic. However, treatment of the LIL cells with IL-2, IL-12 and anti-CD3
      induced these cells to suppress autologous responding cells in MLR (ca. 70%) and
      to kill autologous or allogeneic cells. Low level cytotoxicity could be induced
      by cytokines IL-2, IL-12 or anti-CD3 alone. However, the development of optimum
      MLR suppression and cytotoxicity induction was dependent upon stimulation of the
      LIL cells through the CD3 complex. The co-expression of CD3 and CD56 on LIL was
      also up-regulated by anti-CD3 stimulation in the combination of IL-2 and IL-12.
      Most of the CD3+/CD56+ cells, also expressed CD8. After the magnetic bead
      separation procedure, the cytotoxic activity was found mainly in the
      CD3+/CD56+/CD8+ population. These results suggest that CD3+/CD56+/CD8+ cells can
      be expanded by stimulation through the TCR/CD3 complex in the presence of IL-2
      and IL-12, which results in the suppression of autologous responding cells by a
      cytotoxic mechanism. The proliferative response of the CD3+/CD56+/CD8+ population
      was enhanced by the induction of CD1 molecules on the stimulating cells, and anti
      CD1 mAb were able to block the response in a dose-dependent manner. The
      CD3+/CD56+/CD8+ cells were examined for cytokine production by flow cytometry.
      Cytokines IL-4, TNF-alpha, and IFN-gamma were produced by 91.7%, 29.2%, and 27.4%
      of the cells, respectively.

PMID- 9634198
TI  - DR non-B1 mismatches influence allogeneic MLR-induced TH1- or TH2-like cytokine
      responses in rhesus monkeys.
AB  - Human and nonhuman primates have multiple DR B1 and non-B1 alleles. However, the
      role of mismatched DR non-B1 alleles in primary alloimmune responses is not well
      understood. Macaques, which share close DNA homologies with human MHC genes and
      have a high number of beta-chain genes in the DR subregion, are preeminent
      preclinical models for immunologic studies of transplant tolerance and
      immunosuppression. In this study, we examined the effect of allogeneic MHC Class
      II DRB mismatches in Th1- and Th2-like cytokine responses elicited in one-way MLR
      cultures in rhesus macaques. An ELISPOT method was used to estimate cytokine
      secretion at the single cell level. Molecular typing for DRB1 and DR non-B1
      alleles was performed by a moderate-high resolution PCR-SSP method using a panel
      of 55 primer pairs covering 74 DRB alleles and clusters. Of 35 unrelated
      combinations, 66% had multiple (> or = 2) allelic MM at DRB1 and DR non-B1 with
      no significant correlation between numbers of DRB1 and DR non-B1 mismatches.
      Pairs with 1 or 0 MM were assigned to a mono/null MM group to obtain sufficient
      numbers for statistical analysis. The pairs differing by multiple vs. mono/null
      DRB1 MM showed no significant difference in cytokine prevalence (P = 0.69). In
      contrast, high IFN-gamma/ IL4 SFC ratios were noted in pairs with multiple vs.
      mono/null DR non-B1 MM (p = 0.0009). IFN-gamma/IL-10 spot forming cell (SFC)
      ratios were consistent with IFN-gamma/IL-4 SFC ratios (r = 0.98). Multiple DR non
      B1 mismatches showed a trend towards higher MLR proliferative responses, although
      the stimulation index did not reflect the dominant cytokine response. These
      observations suggest a bias towards Th1-like cytokine production under
      allostimulation with multiple DR non-B1 gene products. Further study of the
      primary structure of DR non-B1 determinants may be helpful in understanding the
      fine molecular mechanisms governing the regulation of cytokine profiles during
      allostimulation in primates.

PMID- 9634199
TI  - Studies on functional status of circulating lymphocytes in unaffected members
      from cancer families.
AB  - That the inheritance of mutations in tumor susceptibility genes alone cannot
      determine risk for developing cancer is now well accepted. Immune functions have
      long been recognized as one of the important risk modifying factors in this
      regard. In an attempt to develop a multiparametric approach to identify high risk
      individuals from cancer families, we have examined NK cell function in unaffected
      members from familial breast cancer families. We have also carried out a parallel
      study of T lymphocyte functions in these individuals. Our studies demonstrate a
      significantly lower NK cell activity in members from cancer families. T
      lymphocyte activity also showed a similar trend, with the unaffected members
      demonstrating a notably lowered T lymphocyte function. In addition the data from
      patients reveals differential sensitivity of NK and T lymphocyte function to the
      disease phenotype. Implications of these observations are discussed.

PMID- 9634200
TI  - HLA and complement factors alleles sharing in Italian couples with recurrent
      spontaneous abortions.
AB  - Recurrent Spontaneous Abortion (RSA) is postulated to be due to several factors
      including immunogenetic mechanisms. Many studies have been conducted on the
      effect of the MHC region in the reproductive phenomena suggesting an
      immunological or genetic involvement in RSA. We studied couples with 3 or more
      abortions among a larger group of couples in which female partners were anti
      cardiolipin antibodies negative, resulting in a population of 43 couples typed
      for HLA-A, B, C, DR, DQ. In 16 of these 43 couples, complement factors C4A, C4B,
      and Bf were typed. The data shows a statistically significant increase of C4B*Q0
      in RSA patients (N = 32) compared with the control population (N = 44) (pc =
      .00147) and also a statistically significant increase of C4B*Q0 sharing in
      aborting couples (43.75%) against the expected sharing rate in the control
      population (1.86%) (p < .001). Frequency increase of C4B*Q0 allele in aborting
      population leads to the hypothesis that an imbalance of complement factors
      expression and activity can have detrimental effects on implantation and embryo
      survival. Additionally, the significant sharing rate of C4B*Q0 in couples with
      RSA could indicate the existence of a gene in linked to this allele predisposing
      to RSA and acting in a recessive manner if present in double copies in the fetus.

PMID- 9634201
TI  - Phenotype analysis in neurological models of human disease.

PMID- 9634202
TI  - Myelin disorders.

PMID- 9634203
TI  - Modelling motor neuron degenerative disease.

PMID- 9634204
TI  - Genetic modelling of muscular dystrophies.

PMID- 9634205
TI  - Transgenic models for Alzheimer's disease.

PMID- 9634206
TI  - Amyotrophic lateral sclerosis: current issues in classification, pathogenesis and
      molecular pathology.
AB  - The classification of amyotrophic lateral sclerosis (ALS) is reconsidered in the
      light of developments in the molecular pathogenesis and histopathology of the
      condition. A current view is encapsulated in the El Escorial World Federation of
      Neurology criteria for the diagnosis of ALS. While intended for research
      purposes, use of these criteria for entry into clinical trials may result in the
      exclusion of some patient groups with related disorders that are likely to share
      aetiological mechanisms but which are not classified as 'definite ALS' or
      'probable ALS'. The relationship between ALS and the more restricted motor
      disorders of progressive lateral sclerosis and progressive muscular atrophy,
      together with cerebral degenerations including ALS-dementia and ALS-related
      frontal lobe dementia, are reviewed. The possibility is raised that they all
      represent syndromic manifestations of a similar pathogenetic cascade whose
      clinical phenotype depends upon the anatomical selectivity of involvement in each
      individual. The new evidence regarding the central role of oxidative stress and
      abnormal glutamatergic neurotransmission in familial and sporadic ALS seem
      applicable across these disorders. New evidence regarding the molecular pathology
      of inclusion bodies in these various syndromes, including ubiquitinated
      inclusions and hyaline conglomerate inclusions, shows striking similarities
      between them. Marked differences in the anatomical distribution of lesions
      determine the predominance and type of motor and cognitive features in each
      syndrome. This concept of a clinicopathological spectrum is potentially of equal
      relevance to other late onset neurodegenerative disorders including multisystem
      atrophies, the Lewy body disorders and various manifestations of Alzheimer's
      disease. It will gain increasing importance as therapies evolve from the
      symptomatic to those directed at underlying pathogenetic events.

PMID- 9634207
TI  - HIV-associated brain pathology: a comparative international study.
AB  - Little is known about the frequency and variation of HIV-associated brain
      pathology in different geographical centres. To assess whether there is an
      association between the frequency of disease and demographic factors we examined
      the neuropathological findings in four European and two American cities. The
      cities included London, Edinburgh, Paris, Budapest, Baltimore and Newark.
      Information was collected on a total of 1144 cases. HIV encephalitis was the most
      common observation in all the centres. although its frequency varied between them
      (P < 0.01). Furthermore, there were significant differences (P < 0.001) between
      the various categories of exposure and the frequency of HIV encephalitis in
      Edinburgh and other centres. The occurrence of toxoplasmosis, progressive
      multifocal leukoencephalolpathy (PML) and cryptococcal infection also differed
      between the various centres (P < 0.01). None of the findings was attributable to
      age, sex, or ethnic origin, but the introduction of anti-retroviral treatment,
      such as Zidovudine, may have been important. Overall, this study highlights
      geographical variability and the potential importance for group of exposure and
      anti-retroviral medication as factors affecting the development of various HIV
      associated brain lesions.

PMID- 9634208
TI  - Prion encephalopathy with insertion of octapeptide repeats: the number of repeats
      determines the type of cerebellar deposits.
AB  - We studied modifications of the molecular layer of the cerebellum in three
      patients with octapeptide repeat insertion (OPRI). Two brothers carrying a six
      OPRI showed only spongiosis in haematoxylin & eosin preparations (H&E), whereas
      immunocytochemical examination (ICC) with an antiprion protein (PrP) antibody
      revealed numerous elongated PrP deposits. The third patient from a family with an
      eight-OPRI had numerous plaques visible in H&E preparations and had been
      diagnosed as Gerstmann-Straussler-Scheinker syndrome. So far, 15 other cases from
      seven families and three individual cases with OPRI have undergone
      neuropathological examination. Characteristic PrP deposits were seen in six other
      cases, two isolated cases with a four- and a seven-OPRI, whereas four cases with
      a six-OPRI came from three different families. Such deposits have never been
      reported in other cases of prion encephalopathy, without OPRI. Genuine plaques
      were observed in five out of the 15 other patients. Interestingly, four had an
      eight-OPRI and one a nine-OPRI. Cases with OPRI are prone to develop different
      PrP deposits: those only visible on ICC are not to be confused with genuine
      plaques visible in H&E preparations. Elongated PrP deposits are present in cases
      with a four- to seven-OPRI, whereas plaques are present when there is an eight-
      or a nine-OPRI. All these cases should be termed prion encephalopathy with OPRI.

PMID- 9634209
TI  - Intracellular pH and chemoresponse to NH4+ in Paramecium.
AB  - Paramecium are attracted to ammonium chloride solutions relative to sodium
      chloride control solutions, but little is known about the mechanisms by which
      attraction is evoked. A known effect of ammonium solutions in other cell types is
      an alteration of intracellular pH. We show here that intracellular pH is elevated
      upon initial exposure to 5 mM NH4Cl, but appears to decline within 10 minutes,
      both in wild type cells and in two mutants which do not show sustained attraction
      to NH4Cl using the standard behavioral assay, the T-maze. We also present
      quantitative values of swimming parameters that underlie the response to NH4Cl.

PMID- 9634211
TI  - Regulation of flagellar length in Chlamydomonas.
AB  - The length of eukaryotic cilia and flagella depends on the cell cycle-regulated
      assembly and disassembly of at least 9 doublet and 2 central microtubules, their
      associated proteins, and the surrounding membrane. In light-synchronized
      Chlamydomonas cells, flagella assembled to 10-14 microm in length near the
      beginning of the light period and they disassembled prior to cell division,
      during the dark period. Flagella on light-synchronized pf18 Chlamydomonas mutants
      grew to 10-12 microm near the beginning of the light period but shortened by 50%
      or more by the end of the light period. Flagellar length was cell-cycle
      regulated: when flagella were amputated at various times during the light period,
      new flagella regenerated to the lengths of control cells at that time of the
      light cycle. The later in the cycle pf18 cells were deflagellated, the shorter
      were the regenerated flagella. Flagellar shortening was not affected, in either
      pf18 or wild-type (wt) cells, by inhibitors of protein synthesis or of
      microtubule assembly, so flagellar length cannot depend on protein turnover.
      Shortening in pf18 was attenuated by Li+, which stimulated flagellar growth in wt
      cells, by red light, by protein kinase inhibitors, and by the Ca2+ channel
      blockers La3+ and Cd2+. Shortening was increased by cAMP, Na+, K+, and EGTA. Ca2+
      CAM blockers did not affect pf18 shortening but they increased shortening in wt
      and fa1 cells. We propose that flagellar length is regulated by a signal
      transduction pathway that is sensitive to Ca2+ levels and red light.

PMID- 9634210
TI  - Changes in the F-actin cytoskeleton during neurosensory bristle development in
      Drosophila: the role of singed and forked proteins.
AB  - Drosophila neurosensory bristle development provides an excellent model system to
      study the role of the actin-based cytoskeleton in polarized cell growth. We used
      confocal fluorescence microscopy of isolated thoracic tissue to characterize
      changes in F-actin that occurred during macrochaete development in wild type
      flies and mutants that have aberrant bristle morphology. At the earliest stages
      in wild type bristle development, cortical patches of F-actin were present, but
      no bundles were observed. Actin bundles began to form at 31% of pupal development
      and became more prominent as development progressed. The F-actin patches
      gradually disappeared and were no longer present by 38% of pupal development. The
      distribution of F-actin in singed3 mutant macrochaetae was indistinguishable from
      wild type bristles until 35% of development when the actin bundles began to splay
      and appear ribbon-like. In forked36a bristles, the mutant phenotype was evident
      at earlier stages of development than the singed3 mutant. Wild type tissue
      stained with antibodies against the forked protein demonstrated that the forked
      protein colocalized with F-actin structures found in early and late stage
      developing macrochaetae. Antibodies against the singed protein showed it appeared
      to localize with F-actin structures only at later stages in development. These
      data suggested that the forked gene product was required for the initiation of
      fiber bundle formation and the singed gene product was required for the
      maintenance of fiber bundle morphology during bristle development. Similar
      analyses of singed3/forked36a double mutants provided additional genetic evidence
      that the forked gene product was required before the singed gene product.
      Further, the analyses suggested that at least one additional crosslinking protein
      was present in these bundles.

PMID- 9634212
TI  - Visualization of kinetochores and analysis of their refractility in crane-fly
      spermatocytes after aldehyde fixation.
AB  - Glutaraldehyde and formaldehyde were used to fix crane-fly spermatocytes for
      observation with differential interference contrast (DIC) microscopy. In aldehyde
      fixed cells, kinetochores exhibit contrast not normally observed in living cells.
      Although the mechanism underlying this result is not understood, the
      visualization of kinetochores as distinct refractile objects opens the way for
      analysis of unstained kinetochores with the light microscope. The analysis of
      kinetochore refractility reported in this paper is made possible by the finding
      that the refractility of chromosomes in formaldehyde-fixed cells decreases as the
      concentration of formaldehyde is increased. In 4% formaldehyde, the refractility
      of chromosomes is matched with that of its surround, chromosomes appear
      invisible, and kinetochores may be analyzed as if chromosomes were not present.
      Kinetochores were imaged with DIC optics, and then digital image analysis was
      performed. Gray-level scans through the highlight and shadow of an individual
      kinetochore parallel to the axis of shear resulted in a curve having a slope
      proportional to the DIC optical path gradient. Curves from autosomal kinetochores
      imaged in anaphase had slopes approximately one-half those recorded at metaphase
      under identical optical conditions. By contrast, kinetochore thicknesses (defined
      as the distance between the peak and the valley of a gray-level scan) at those
      two stages were not significantly different. These data suggest a loss of dry
      mass from autosomal kinetochores during anaphase. Neither the refractility nor
      thickness of lagging sex kinetochores varied as autosomes went through anaphase.
      The conclusion drawn from these findings is that the decreased refractility of
      autosomal kinetochores in anaphase is movement-related.

PMID- 9634213
TI  - Actin-dependent anterograde movement of growth-cone-like structures along growing
      hippocampal axons: a novel form of axonal transport?
AB  - In time-lapse video recordings of hippocampal neurons in culture, we have
      identified previously uncharacterized structures, nicknamed "waves," that exhibit
      lamellipodial activity closely resembling that of growth cones, but which
      periodically emerge at the base of axons and travel distally at an average rate
      of 3 microm/min. In electron micrographs of identified waves, the cortical region
      of the axon appears expanded to either side, forming lamellipodia like those at
      growth cones. No other gross differences were noted in the ultrastructural
      features of the axon shaft at the site of a wave. Immunocytochemistry revealed
      that waves contain a marked concentration of F-actin, GAP-43, cortactin, and
      ezrin or a related protein, constituents that are also concentrated in growth
      cones. Treatment with the actin-disrupting agent cytochalasin B caused a
      reversible collapse of lamellipodia and cessation of the forward movement of
      individual waves along the axon, indicating that their anterograde transport is
      dependent on intact actin filaments. Treatment with the microtubule
      depolymerizing agent nocodazole led to a rapid disorganization of wave structure
      and a subsequent suppression of wave activity that may reflect a role of
      microtubules in actin organization. The results suggest that actin and other
      cytoskeletal components concentrated in growth cones may be transported together
      as growth-cone-like structures from the cell body to the axon tip via an actin
      dependent mechanism.

PMID- 9634214
TI  - Rigor-type mutation in the kinesin-related protein HsEg5 changes its subcellular
      localization and induces microtubule bundling.
AB  - HsEg5 is a human kinesin-related motor protein essential for the formation of a
      bipolar mitotic spindle. It interacts with the mitotic centrosomes in a
      phosphorylation-dependent manner. To investigate further the mechanisms involved
      in targetting HsEg5 to the spindle apparatus, we expressed various mutants of
      HsEg5 in HeLa cells. All these mutants share a mutation of Thr-112 in the N
      terminal motor domain, resulting in the inactivation of the ATP binding domain.
      In vitro, the HsEg5-T112N mutant motor domain showed a nucleotide-independent
      microtubule association, typical of a kinesin protein binding to microtubules in
      a rigor state. In vivo, overexpression of the HsEg5 rigor mutant in HeLa cells
      induced, in interphase, microtubule bundling, and, in mitosis, the formation of
      monopolar mitotic spindles similar to those observed after microinjection of anti
      HsEg5 antibodies. Localization of the HsEg5 rigor mutant on cytoplasmic
      microtubules did not require the C-terminal tail domain but was lost when the
      stalk domain was also deleted. Sucrose gradient centrifugation experiments showed
      that microtubule bundling was most likely caused by the binding of HsEg5 mutants
      in a dimeric state. These results demonstrate that the precise subcellular
      localization of HsEg5 in vivo is regulated not only by the phosphorylation of the
      tail domain but also by the oligomeric state of the protein.

PMID- 9634215
TI  - Altered drug resistance of microtubules in cells exposed to infrared light
      pulses: are microtubules the "nerves" of cells?
AB  - This article describes the first quantitative assay of the response of an entire
      population of cultured mammalian cells to a pulsating near-infrared signal. The
      assay measures the change of resistance to nocodazole of reconstituted
      cytoplasmic asters of irradiated cells. Using this assay on CV1 cells, I obtained
      results suggesting that pulsating near-infrared signals of 1 s pulse length
      reduced the stability of the radial microtubules around the centrosome. The
      results are consistent with the interpretation that the centrosome responded to
      the light by sending signals along its radial array of microtubules whose
      stability was then altered. The results may be an example of a more general
      function of the centrosome to integrate exogenous signals and send response
      signals along microtubules to various sites within the cell.

PMID- 9634216
TI  - Pharmacological and genetic evidence for a role of rootlet and phycoplast
      microtubules in the positioning and assembly of cleavage furrows in Chlamydomonas
      reinhardtii.
AB  - In Chlamydomonas reinhardtii, specialized cytoskeletal structures known as
      rootlet microtubules are present throughout interphase and mitosis. During
      cytokinesis, an array of microtubules termed the phycoplast is nucleated from
      rootlet microtubules and forms coincidentally with the cleavage furrow [Johnson
      and Porter, 1968: J. Cell Biol. 38:403-425; Holmes and Dutcher, 1989: J. Cell
      Sci. 94:273-285; Gaffel and el-Gammel, 1990: Protoplasma 156:139-148; Schibler
      and Huang, 1991: J. Cell Biol. 113:605-614]. We have obtained two independent
      lines of evidence that support the hypothesis that the rootlet and phycoplast
      microtubules play a direct role in cleavage furrow placement and assembly. First,
      the destabilization of spindle and phycoplast microtubules by pharmacological
      agents was accompanied by the aberrant distribution of actin and a failure of
      cytokinesis. Second, we characterized mutant strains that failed to complete
      cytokinesis properly. Actin and myosin were mislocalized to additional rootlet
      microtubules in the cyt2-1 strain, and this mislocalization was correlated with
      the presence of additional cleavage furrows. This evidence suggests that
      microtubules are necessary for the correct positioning and assembly of functional
      cleavage furrows in C. reinhardtii.

PMID- 9634217
TI  - When moderation turns to greed.

PMID- 9634218
TI  - Espionage verdict prompts call for retraction of polymerase paper.

PMID- 9634219
TI  - NIH 'should help sharing of research tools'.

PMID- 9634220
TI  - French researchers reject reform plans...as medical agency agrees to a
      compromise.

PMID- 9634221
TI  - Harvard's 'oncomouse' fails to win Canadian patent.

PMID- 9634222
TI  - Swiss reject curbs on genetic engineering.

PMID- 9634223
TI  - British biotech responds to allegations.

PMID- 9634224
TI  - Ethical discourse by science-in-fiction.

PMID- 9634225
TI  - Blueprint for the white plague.

PMID- 9634226
TI  - Evolutionary biology. Help and you shall be helped.

PMID- 9634227
TI  - Brain, heart and stress.

PMID- 9634228
TI  - Chemokines beyond inflammation.

PMID- 9634229
TI  - Sound localization and neurons.

PMID- 9634230
TI  - Deciphering the biology of Mycobacterium tuberculosis from the complete genome
      sequence.
AB  - Countless millions of people have died from tuberculosis, a chronic infectious
      disease caused by the tubercle bacillus. The complete genome sequence of the best
      characterized strain of Mycobacterium tuberculosis, H37Rv, has been determined
      and analysed in order to improve our understanding of the biology of this slow
      growing pathogen and to help the conception of new prophylactic and therapeutic
      interventions. The genome comprises 4,411,529 base pairs, contains around 4,000
      genes, and has a very high guanine + cytosine content that is reflected in the
      biased amino-acid content of the proteins. M. tuberculosis differs radically from
      other bacteria in that a very large portion of its coding capacity is devoted to
      the production of enzymes involved in lipogenesis and lipolysis, and to two new
      families of glycine-rich proteins with a repetitive structure that may represent
      a source of antigenic variation.

PMID- 9634231
TI  - Chemical processing in the coma as the source of cometary HNC.
AB  - The discovery of hydrogen isocyanide (HNC) in comet Hyakutake with an abundance
      (relative to hydrogen cyanide, HCN) similar to that seen in dense interstellar
      clouds raised the possibility that these molecules might be surviving
      interstellar material. The preservation of material from the Sun's parent
      molecular cloud would provide important constraints on the processes that took
      place in the protostellar nebula. But another possibility is that HNC is produced
      by photochemical processes in the coma, which means that its abundance could not
      be used as a direct constraint on conditions in the early Solar System. Here we
      show that the HNC/HCN ratio determined for comet Hale-Bopp varied with
      heliocentric distance in a way that matches the predictions of models of gas
      phase chemical production of HNC in the coma, but cannot be explained if the HNC
      molecules were coming from the comet's nucleus. We conclude that HNC forms mainly
      by chemical reactions in the coma, and that such reactions need to be considered
      when attempting to deduce the composition of the nucleus from observations of the
      coma.

PMID- 9634232
TI  - Evolution of indirect reciprocity by image scoring.
AB  - Darwinian evolution has to provide an explanation for cooperative behaviour.
      Theories of cooperation are based on kin selection (dependent on genetic
      relatedness), group selection and reciprocal altruism. The idea of reciprocal
      altruism usually involves direct reciprocity: repeated encounters between the
      same individuals allow for the return of an altruistic act by the recipient. Here
      we present a new theoretical framework, which is based on indirect reciprocity
      and does not require the same two individuals ever to meet again. Individual
      selection can nevertheless favour cooperative strategies directed towards
      recipients that have helped others in the past. Cooperation pays because it
      confers the image of a valuable community member to the cooperating individual.
      We present computer simulations and analytic models that specify the conditions
      required for evolutionary stability of indirect reciprocity. We show that the
      probability of knowing the 'image' of the recipient must exceed the cost-to
      benefit ratio of the altruistic act. We propose that the emergence of indirect
      reciprocity was a decisive step for the evolution of human societies.

PMID- 9634233
TI  - Selective representation of relevant information by neurons in the primate
      prefrontal cortex.
AB  - The severe limitation of the capacity of working memory, the ability to store
      temporarily and manipulate information, necessitates mechanisms that restrict
      access to it. Here we report tests to discover whether the activity of neurons in
      the prefrontal (PF) cortex, the putative neural correlate of working memory,
      might reflect these mechanisms and preferentially represent behaviourally
      relevant information. Monkeys performed a 'delayed-matching-to-sample' task with
      an array of three objects. Only one of the objects in the array was relevant for
      task performance and the monkeys needed to find that object (the target) and
      remember its location. For many PF neurons, activity to physically identical
      arrays varied with the target location; the location of the non-target objects
      had little or no influence on activity. Information about the target location was
      present in activity as early as 140ms after array onset. Also, information about
      which object was the target was reflected in the sustained activity of many PF
      neurons. These results suggest that the prefrontal cortex is involved in
      selecting and maintaining behaviourally relevant information.

PMID- 9634234
TI  - Gli/Zic factors pattern the neural plate by defining domains of cell
      differentiation.
AB  - Three cell types differentiate in the early frog neural plate: neural crest at
      the lateral edges, floorplate at the midline and primary neurons in three
      bilateral stripes. Floorplate cells and ventral neurons are induced by Sonic
      hedgehog (Shh) and neural crest and dorsal neurons are induced by epidermal
      factors such as bone morphogenetic proteins (BMPs). Neurogenesis in a subset of
      cells within the stripes involves lateral inhibition. However, the process by
      which pools of precursors are defined in stereotypic domains in response to
      inductive signals is unknown. Here we show that frog Zic2 encodes a zinc-finger
      transcription factor of the Gli superfamily which is expressed in stripes that
      alternate with those in which primary neurons differentiate and overlap the
      domains of floorplate and neural crest progenitors. Zic2 inhibits neurogenesis
      and induces neural crest differentiation. Conversely, Gli proteins are widely
      expressed, induce neurogenesis and inhibit neural crest differentiation. Zic2 is
      therefore a vertebrate pre-pattern gene, encoding anti-neurogenic and crest
      inducing functions that counteract the neurogenic but not the floorplate-inducing
      activity of Gli proteins. We propose that the combined function of Gli/Zic genes
      responds to inductive signals and induces patterned neural cell differentiation.

PMID- 9634235
TI  - Molecular identification of a hyperpolarization-activated channel in sea urchin
      sperm.
AB  - Sea urchin eggs attract sperm through chemotactic peptides, which evoke complex
      changes in membrane voltage and in the concentrations of cyclic AMP, cyclic GMP
      and Ca2+ ions The intracellular signalling pathways and their cellular targets
      are largely unknown. We have now cloned, from sea urchin testis, the
      complementary DNA encoding a channel polypeptide, SPIH. Functional expression of
      SPIH gives rise to weakly K+-selective hyperpolarization-activated channels,
      whose activity is enhanced by the direct action of cAMP. Thus, SPIH is under the
      dual control of voltage and cAMP. The SPIH channel, which is confined to the
      sperm flagellum, may be involved in the control of flagellar beating. SPIH
      currents exhibit all the hallmarks of hyperpolarization-activated currents (Ih),
      which participate in the rhythmic firing of central neurons, control pacemaking
      in the heart, and curtail saturation by bright light in retinal photoreceptors.
      Because of their sequence and functional properties, Ih channels form a class of
      their own within the superfamily of voltage-gated and cyclic-nucleotide-gated
      channels.

PMID- 9634236
TI  - A family of hyperpolarization-activated mammalian cation channels.
AB  - Pacemaker activity of spontaneously active neurons and heart cells is controlled
      by a depolarizing, mixed Na+/K+ current, named Ih (or I(f) in the sinoatrial node
      of the heart). This current is activated on hyperpolarization of the plasma
      membrane. In addition to depolarizing pacemaker cells, Ih is involved in
      determining the resting membrane potential of neurons and provides a mechanism to
      limit hyperpolarizing currents in these cells. Hormones and neurotransmitters
      that induce a rise in cyclic AMP levels increase Ih by a mechanism that is
      independent of protein phosphorylation, and which involves direct binding of the
      cyclic nucleotide to the channel that mediates Ih. Here we report the molecular
      cloning and functional expression of the gene encoding a hyperpolarization
      activated cation channel (HAC1) that is present in brain and heart. This channel
      exhibits the general properties of Ih channels. We have also identified full
      length sequences of two related channels, HAC2 and HAC3, that are specifically
      expressed in the brain, indicating the existence of a family of hyperpolarization
      activated cation channels.

PMID- 9634237
TI  - The chemokine receptor CXCR4 is essential for vascularization of the
      gastrointestinal tract.
AB  - Vascularization of organs generally occurs by remodelling of the preexisting
      vascular system during their differentiation and growth to enable them to perform
      their specific functions during development. The molecules required by early
      vascular systems, many of which are receptor tyrosine kinases and their ligands,
      have been defined by analysis of mutant mice. As most of these mice die during
      early gestation before many of their organs have developed, the molecules
      responsible for vascularization during organogenesis have not been identified.
      The cell-surface receptor CXCR4 is a seven-transmembrane-spanning, G-protein
      coupled receptor for the CXC chemokine PBSF/SDF-1 (for pre-B-cell growth
      stimulating factor/stromal-cell-derived factor), which is responsible for B-cell
      lymphopoiesis, bone-marrow myelopoiesis and cardiac ventricular septum formation.
      CXCR4 also functions as a co-receptor for T-cell-line tropic human
      immunodeficiency virus HIV-1. Here we report that CXCR4 is expressed in
      developing vascular endothelial cells, and that mice lacking CXCR4 or PBSF/SDF-1
      have defective formation of the large vessels supplying the gastrointestinal
      tract. In addition, mice lacking CXCR4 die in utero and are defective in vascular
      development, haematopoiesis and cardiogenesis, like mice lacking PBSF/SDF-1,
      indicating that CXCR4 is a primary physiological receptor for PBSF/SDF-1. We
      conclude that PBSF/SDF-1 and CXCR4 define a new signalling system for organ
      vascularization.

PMID- 9634239
TI  - Histone macroH2A1 is concentrated in the inactive X chromosome of female mammals.
AB  - In female mammals one of the X chromosomes is rendered almost completely
      transcriptionally inactive to equalize expression of X-linked genes in males and
      females. The inactive X chromosome is distinguished from its active counterpart
      by its condensed appearance in interphase nuclei, late replication, altered DNA
      methylation, hypoacetylation of histone H4, and by transcription of a large cis
      acting nuclear RNA called Xist. Although it is believed that the inactivation
      process involves the association of specific protein(s) with the chromatin of the
      inactive X, no such proteins have been identified. We discovered a new gene
      family encoding a core histone which we called macroH2A (mH2A). The amino
      terminal third of mH2A proteins is similar to a full-length histone H2A, but the
      remaining two-thirds is unrelated to any known histones. Here we show that an
      mH2A1 subtype is preferentially concentrated in the inactive X chromosome of
      female mammals. Our results link X inactivation with a major alteration of the
      nucleosome, the primary structural unit of chromatin.

PMID- 9634238
TI  - Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar
      development.
AB  - Chemokines and their receptors are important in cell migration during
      inflammation, in the establishment of functional lymphoid microenvironments, and
      in organogenesis. The chemokine receptor CXCR4 is broadly expressed in cells of
      both the immune and the central nervous systems and can mediate migration of
      resting leukocytes and haematopoietic progenitors in response to its ligand, SDF
      1. CXCR4 is also a major receptor for strains of human immunodeficiency virus-1
      (HIV-1) that arise during progression to immunodeficiency and AIDS dementia. Here
      we show that mice lacking CXCR4 exhibit haematopoietic and cardiac defects
      identical to those of SDF-1-deficient mice, indicating that CXCR4 may be the only
      receptor for SDF-1. Furthermore, fetal cerebellar development in mutant animals
      is markedly different from that in wild-type animals, with many proliferating
      granule cells invading the cerebellar anlage. This is, to our knowledge, the
      first demonstration of the involvement of a G-protein-coupled chemokine receptor
      in neuronal cell migration and patterning in the central nervous system. These
      results may be important for designing strategies to block HIV entry into cells
      and for understanding mechanisms of pathogenesis in AIDS dementia.

PMID- 9634240
TI  - A piece of my mind. Tribute.

PMID- 9634241
TI  - Medical groups say physicians can help keep kids from killing.

PMID- 9634242
TI  - Compensation for injured research subjects.

PMID- 9634243
TI  - RAID teams to respond to terrorism threat. Rapid assessment and initial
      detection.

PMID- 9634244
TI  - From the Centers for Disease Control and Prevention. Boat-propeller-related
      injuries--Texas, 1997.

PMID- 9634245
TI  - From the Centers for Disease Control and Prevention. Nosocomial Ralstonia
      pickettii colonization associated with intrinsically contaminated saline solution
      -Los Angeles, California, 1998.

PMID- 9634246
TI  - From the Centers for Disease Control and Prevention. Corneal decompensation after
      intraocular ophthalmic surgery--Missouri, 1998.

PMID- 9634247
TI  - From the Centers for Disease Control and Prevention. Pregnancy-related death
      associated with heparin and aspirin treatment for infertility, 1996.

PMID- 9634248
TI  - What price survival? The future of Blue Cross and Blue Shield.

PMID- 9634249
TI  - Rapid opioid detoxification.

PMID- 9634250
TI  - Rapid opioid detoxification.

PMID- 9634251
TI  - Rapid opioid detoxification.

PMID- 9634252
TI  - Risk of fetal anomalies with exposure to selective serotonin reuptake inhibitors.

PMID- 9634253
TI  - Risk of fetal anomalies with exposure to selective serotonin reuptake inhibitors.

PMID- 9634254
TI  - Use of serotonin reuptake inhibitors by women of childbearing potential.

PMID- 9634255
TI  - Antiretroviral therapy and improving AIDS survival.

PMID- 9634256
TI  - Space medicine in peer-reviewed journals.

PMID- 9634257
TI  - Merck-sponsored simvastatin (Zocor) compliance program for patients using Wal
      Mart Pharmacy: of benefit to whom?

PMID- 9634258
TI  - Management of pain in elderly patients with cancer. SAGE Study Group. Systematic
      Assessment of Geriatric Drug Use via Epidemiology.
AB  - CONTEXT: Cancer pain can be relieved with pharmacological agents as indicated by
      the World Health Organization (WHO). All too frequently pain management is
      reported to be poor. OBJECTIVE: To evaluate the adequacy of pain management in
      elderly and minority cancer patients admitted to nursing homes. DESIGN:
      Retrospective, cross-sectional study. SETTING: A total of 1492 Medicare-certified
      and/or Medicaid-certified nursing homes in 5 states participating in the Health
      Care Financing Administration's demonstration project, which evaluated the
      implementation of the Resident Assessment Instrument and its Minimum Data Set.
      STUDY POPULATION: A group of 13 625 cancer patients aged 65 years and older
      discharged from the hospital to any of the facilities from 1992 to 1995. Data
      were from the multilinked Systematic Assessment of Geriatric Drug Use via
      Epidemiology (SAGE) database. MAIN OUTCOME MEASURES: Prevalence and predictors of
      daily pain and of analgesic treatment. Pain assessment was based on patients'
      report and was completed by a multidisciplinary team of nursing home personnel
      that observed, over a 7-day period, whether each resident complained or showed
      evidence of pain daily. RESULTS: A total of 4003 patients (24%, 29%, and 38% of
      those aged > or =85 years, 75 to 84 years, and 65 to 74 years, respectively)
      reported daily pain. Age, gender, race, marital status, physical function,
      depression, and cognitive status were all independently associated with the
      presence of pain. Of patients with daily pain, 16% received a WHO level 1 drug,
      32% a WHO level 2 drug, and only 26% received morphine. Patients aged 85 years
      and older were less likely to receive morphine or other strong opiates
      [corrected] than those aged 65 to 74 years (13% vs 38%, respectively). More than
      a quarter of patients (26%) in daily pain did not receive any analgesic agent.
      Patients older than 85 years in daily pain were also more likely to receive no
      analgesia (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.13-1.73). Other
      independent predictors of failing to receive any analgesic agent were minority
      race (OR, 1.63; 95% CI, 1.18-2.26 for African Americans), low cognitive
      performance (OR, 1.23; 95% CI, 1.05-1.44), and the number of other medications
      received (OR, 0.65; 95% CI, 0.5-0.84 for 11 or more medications). CONCLUSIONS:
      Daily pain is prevalent among nursing home residents with cancer and is often
      untreated, particularly among older and minority patients.

PMID- 9634259
TI  - Physicians disciplined for sex-related offenses.
AB  - CONTEXT: Physicians who abuse their patients sexually cause immense harm, and,
      therefore, the discipline of physicians who commit any sex-related offenses is an
      important public health issue that should be examined. OBJECTIVES: To determine
      the frequency and severity of discipline against physicians who commit sex
      related offenses and to describe the characteristics of these physicians. DESIGN
      AND SETTING: Analysis of sex-related orders from a national database of
      disciplinary orders taken by state medical boards and federal agencies. SUBJECTS:
      A total of 761 physicians disciplined for sex-related offenses from 1981 through
      1996. MAIN OUTCOME MEASURES: Rate and severity of discipline over time for sex
      related offenses and specialty, age, and board certification status of
      disciplined physicians. RESULTS: The number of physicians disciplined per year
      for sex-related offenses increased from 42 in 1989 to 147 in 1996, and the
      proportion of all disciplinary orders that were sex related increased from 2.1%
      in 1989 to 4.4% in 1996 (P<.001 for trend). Discipline for sex-related offenses
      was significantly more severe (P<.001) than for non-sex-related offenses, with
      71.9% of sex-related orders involving revocation, surrender, or suspension of
      medical license. Of 761 physicians disciplined, the offenses committed by 567
      (75%) involved patients, including sexual intercourse, rape, sexual molestation,
      and sexual favors for drugs. As of March 1997, 216 physicians (39.9%) disciplined
      for sex-related offenses between 1981 and 1994 were licensed to practice.
      Compared with all physicians, physicians disciplined for sex-related offenses
      were more likely to practice in the specialties of psychiatry, child psychiatry,
      obstetrics and gynecology, and family and general practice (all P<.001) than in
      other specialties and were older than the national physician population, but were
      no different in terms of board certification status. CONCLUSIONS: Discipline
      against physicians for sex-related offenses is increasing over time and is
      relatively severe, although few physicians are disciplined for sexual offenses
      each year. In addition, a substantial proportion of physicians disciplined for
      these offenses are allowed to either continue to practice or return to practice.

PMID- 9634260
TI  - Physicians disciplined by a state medical board.
AB  - CONTEXT: State medical boards discipline several thousand physicians each year.
      Although certain subgroups, such as those disciplined for malpractice, substance
      use, or sexual abuse, have been studied, little is known about disciplined
      physicians as a group. OBJECTIVE: To assess the offenses, contributing factors,
      and type of discipline of a consecutive series of disciplined physicians. DESIGN:
      Case-control study on publicly available data matching 375 disciplined physicians
      with 2 groups of control physicians, one matched solely by locale, and a second
      matched for sex, type of practice, and locale. SUBJECTS: All disciplined
      physicians publicly reported by the Medical Board of California from October 1995
      through April 1997. MAIN OUTCOME MEASURES: Characteristics of disciplined
      physicians, offenses leading to discipline, and type of discipline. RESULTS: A
      total of 375 physicians licensed by the Medical Board of California
      (approximately 0.24% per year) were disciplined for 465 offenses. The most
      frequent causes for discipline were negligence or incompetence (34%), abuse of
      alcohol or other drugs (14%), inappropriate prescribing practices (11%),
      inappropriate contact with patients (10%), and fraud (9%). Discipline imposed was
      revocation of medical license (21%), actual suspension of license (13%), stayed
      suspension of license (45%), and reprimand (21%). Type of offense was
      significantly associated with severity of discipline (P=.03). In logistic
      regression models comparing disciplined physicians with controls matched by
      locale, board discipline was significantly associated with physicians' sex (odds
      ratio [OR] for women, 0.44; 95% confidence interval [CI], 0.28-0.70) and
      involvement in direct patient care (OR, 2.56; 95% CI, 1.75-3.75). In the
      regression model with additional matching criteria, disciplinary action was
      negatively associated with specialty board certification (OR, 0.42; 95% CI, 0.29
      0.60) and positively associated with being in practice more than 20 years (OR,
      2.02; 95% CI, 1.39-2.92). CONCLUSIONS: A small but substantial proportion of
      physicians is disciplined each year for a variety of offenses. Further study of
      disciplined physicians is necessary to identify physicians at high risk for
      offenses leading to disciplinary action and to develop effective interventions to
      prevent these offenses.

PMID- 9634261
TI  - Trends in HIV incidence among young adults in the United States.
AB  - CONTEXT: Behaviors that result in potential exposure to human immunodeficiency
      virus (HIV) usually begin in adolescence or young adulthood, but trends in HIV
      incidence in young people remain unclear. OBJECTIVE: To estimate trends in HIV
      incidence in teenagers and young adults. DESIGN AND SETTING: Back-calculation of
      past HIV incidence in persons born between 1960 and 1974 using US national
      acquired immunodeficiency syndrome (AIDS) incidence data and estimates of the
      distribution of times between HIV infection and AIDS. MAIN OUTCOME MEASURES:
      Incidence and prevalence of HIV in 1988 and 1993 in persons aged 20 and 25 years,
      respectively, in each of those years. RESULTS: As of January 1993, about 22000
      men and 11000 women aged 18 to 22 years were living with HIV infection in the
      United States. Homosexual contact was the leading route of infection among young
      men. Heterosexual contact was the leading route of infection among young women.
      The HIV incidence attributed to homosexual contact or injection drug use
      decreased among persons aged 20 and 25 years between 1988 and 1993, but HIV
      incidence attributed to heterosexual contact was stable or increasing. Notably,
      in men aged 20 and 25 years, HIV prevalence declined by about 50% in white men
      but was relatively stable in black and Hispanic men. In contrast, HIV prevalence
      in women aged 20 and 25 years rose by 36% and 45%, respectively, because of
      increasing heterosexual transmission. Overall, HIV prevalence in persons aged 20
      and 25 years declined by only 14% between 1988 and 1993. CONCLUSIONS: In young
      persons, HIV incidence in homosexual men and injection drug users was slowing by
      1993; this favorable trend was offset by increasing heterosexual transmission,
      especially in minorities.

PMID- 9634262
TI  - Effect of a garlic oil preparation on serum lipoproteins and cholesterol
      metabolism: a randomized controlled trial.
AB  - CONTEXT: Garlic-containing drugs have been used in the treatment of
      hypercholesterolemia even though their efficacy is not generally established.
      Little is known about the mechanisms of action of the possible effects on
      cholesterol in humans. OBJECTIVE: To estimate the hypocholesterolemic effect of
      garlic oil and to investigate the possible mechanism of action. DESIGN: Double
      blind, randomized, placebo-controlled trial. SETTING: Outpatient lipid clinic.
      PATIENTS: We investigated 25 patients (mean age, 58 years) with moderate
      hypercholesterolemia. INTERVENTION: Steam-distilled garlic oil preparation (5 mg
      twice a day) vs placebo each for 12 weeks with wash-out periods of 4 weeks. MAIN
      OUTCOME MEASURES: Serum lipoprotein concentrations, cholesterol absorption, and
      cholesterol synthesis. RESULTS: Baseline lipoprotein profiles were (mean [SD]):
      total cholesterol, 7.53 (0.75) mmol/L (291 [29] mg/dL); low-density lipoprotein
      cholesterol (LDL-C), 5.35 (0.78) mmol/L (207 [30] mg/dL); high-density
      lipoprotein cholesterol (HDL-C), 1.50 (0.41) mmol/L (58 [16] mg/dL); and
      triglycerides, 1.45 (0.73) mmol/L (127 [64] mg/ dL). Lipoprotein levels were
      virtually unchanged at the end of both treatment periods (mean difference [95%
      confidence interval]): total cholesterol, 0.085 (-0.201 to 0.372) mmol/L (3.3 [
      7.8 to 14.4] mg/dL), P=.54; LDL-C, 0.001 (-0.242 to 0.245) mmol/L (0.04 [-9.4 to
      9.5] mg/dL), P=.99; HDL-C, 0.050 (-0.028 to 0.128) mmol/L (1.9 [-1.1 to 4.9]
      mg/dL), P=.20; triglycerides, 0.047 (-0.229 to 0.135) mmol/L (4.2 [-20.3 to
      12.0]) mg/dL, P=.60. Cholesterol absorption (37.5% [10.5%] vs 38.3% [10.7%0],
      P=.58), cholesterol synthesis (12.7 [6.5] vs 13.4 [6.6] mg/kg of body weight per
      day, P=.64), mevalonic acid excretion (192 [66] vs 187 [66] microg/d, P=.78), and
      changes in the ratio of lathosterol to cholesterol in serum (4.4% [24.3%] vs
      10.6% [21.1%], P=.62) were not different in garlic and placebo treatment.
      CONCLUSIONS: The commercial garlic oil preparation investigated had no influence
      on serum lipoproteins, cholesterol absorption, or cholesterol synthesis. Garlic
      therapy for treatment of hypercholesterolemia cannot be recommended on the basis
      of this study.

PMID- 9634263
TI  - Are beta-blockers efficacious as first-line therapy for hypertension in the
      elderly? A systematic review.
AB  - OBJECTIVE: To assess antihypertensive efficacy of beta-blockers and their effects
      on cardiovascular morbidity and mortality and all-cause morbidity compared with
      diuretics in elderly patients with hypertension. DATA SOURCE: A MEDLINE search of
      English-language articles published between January 1966 and January 1998 using
      the terms hypertension (drug therapy) and elderly or aged or geriatric, and
      cerebrovascular or cardiovascular diseases, and morbidity or mortality.
      References from identified articles were also reviewed. DATA SELECTION:
      Randomized trials lasting at least 1 year, which used as first-line agents
      diuretics and/or beta-blockers, and reported morbidity and mortality outcomes in
      elderly patients with hypertension. DATA SYNTHESIS AND RESULTS: Ten trials
      involving a total of 16164 elderly patients (> or =60 years) were included. Two
      thirds of the patients assigned to diuretics were well controlled on monotherapy,
      whereas less than a third of the patients assigned to beta-blockers were well
      controlled on monotherapy. Diuretic therapy was superior to beta-blockade with
      regard to all end points and was effective in preventing cerebrovascular events
      (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.51-0.72), fatal stroke
      (OR, 0.67; 95% CI, 0.49-0.90), coronary heart disease (OR, 0.74; 95% CI, 0.64
      0.85), cardiovascular mortality (OR, 0.75; 95% CI, 0.64-0.87), and all-cause
      mortality (OR, 0.86; 95% CI, 0.77-0.96). In contrast, beta-blocker therapy only
      reduced the odds for cerebrovascular events (OR, 0.75; 95% CI, 0.57-0.98) but was
      ineffective in preventing coronary heart disease, cardiovascular mortality, and
      all-cause mortality (ORs, 1.01, 0.98, and 1.05, respectively). CONCLUSIONS: In
      contrast to diuretics, which remain the standard first-line therapy, beta
      blockers, until proven otherwise, should no longer be considered appropriate
      first-line therapy of uncomplicated hypertension in the elderly hypertensive
      patient.

PMID- 9634264
TI  - Sleepiness, driving, and motor vehicle crashes. Council on Scientific Affairs,
      American Medical Association.
AB  - OBJECTIVE: To assess the contribution of driver sleepiness to highway crashes and
      review recent recommendations to change federal hours-of-service regulations for
      commercial motor vehicle drivers. DATA SOURCES: Information was derived from a
      search of the MEDLINE, Transportation Research Information Service (TRIS), and
      Bibliographic Electronic Databases of Sleep (BEDS) databases from 1975 through
      1997 and from manual review of the reference lists in relevant journal articles,
      government publications, conference proceedings, and textbooks. DATA SYNTHESIS:
      Driver sleepiness is a causative factor in 1% to 3% of all US motor vehicle
      crashes. Surveys of the prevalence of sleepy behavior in drivers suggest that
      sleepiness may be a more common cause of highway crashes than is reflected in
      these estimates. About 96% of sleep-related crashes involve passenger vehicle
      drivers and 3% involve drivers of large trucks. Risk factors include youth, shift
      work, alcohol and other drug use, over-the-counter and prescription medications,
      and sleep disorders. CONCLUSIONS: Increased awareness of the relationship between
      sleepiness and motor vehicle crashes will promote the health and safety of
      drivers and highway users. Physicians can contribute by encouraging good sleep
      habits, recognizing and treating sleep-related problems, and counseling patients
      about the risks of driving while sleepy. To protect public health and safety, the
      American Medical Association recommends continued research on devices and
      technologies to detect the signs of sleepiness and prevent the deterioration of
      driver alertness and performance. Educational programs about the risks of falling
      asleep while driving are needed for physicians, the public, and commercial truck
      drivers.

PMID- 9634265
TI  - Undertreatment of cancer pain in elderly patients.

PMID- 9634266
TI  - The role of the medical profession in physician discipline.

PMID- 9634267
TI  - JAMA patient page: auto safety.

PMID- 9634268
TI  - [General principles of macroscopic examination of kidney tumors].
AB  - We describe the main methods of gross examination of renal tumours. The
      pathologic result should refer to the TNM staging, which was achieved by UICC and
      AJCC in March, '97.

PMID- 9634269
TI  - Gastric cancer.

PMID- 9634270
TI  - Evidence-based reviews.

PMID- 9634272
TI  - British Society for Haematology annual scientific meeting. Glasgow, United
      Kingdom, 27-30 April 1998. Proceedings and abstracts.

PMID- 9634271
TI  - Assessing the rigidity and retention of two new types of root canal posts.

PMID- 9634273
TI  - The quality measurement matrix: an elegant planning and educational tool.

PMID- 9634274
TI  - [Positive-pressure noninvasive artificial ventilation by nasal mask and its role
      in pneumology].

PMID- 9634275
TI  - [Bronchodilators in COPD--monotherapy or combined? (The annual ERS congress-
      Stockholm, Sept. 1996). European Respiratory Society].

PMID- 9634276
TI  - [Laparoscopic cholecystectomy in the hands of the left-handed surgeon. A
      technical note].

PMID- 9634277
TI  - [The statutes of the Romanian Society of Surgery].

PMID- 9634278
TI  - Direct enantiomeric separation of mianserin and 6-azamianserin derivatives using
      chiral stationary phases.
AB  - The direct enantiomeric separation of mianserin and 6-azamianserin and some of
      their derivatives, respectively, by means of HPLC using two different chiral
      selectors was investigated. For the cellulose-based Chiralcel OD column, a strong
      dependence of the lipophilicity of the compounds tested on the retention
      behaviour was observed. To some extent, this was also found for the enantiomeric
      separation on the amylose-based Chiralpak AD column. In some cases a
      complementary behaviour of these two phases was observed: racemic mixtures that
      could not be separated by one column could be resolved by the other one.

PMID- 9634279
TI  - Capillary electrophoretic and high-performance liquid chromatographic studies of
      the enantioselective separation of alpha1-adrenoreceptor antagonists.
AB  - Capillary electrophoresis (CE) and chiral stationary phase (CSP) HPLC methods
      were investigated for the determination of enantiomeric purity of alpha1
      adrenoreceptor antagonists related to WB 4101. In the CE study, the
      enantioseparation of the analytes was performed by studying the effect of
      different types of cyclodextrin in the buffer, namely heptakis (2,6-di-O-methyl)
      beta-cyclodextrin (DMCD), hydroxypropyl-beta-cyclodextrin (HPCD) and beta
      cyclodextrin (beta-CD). HPCD was found to be the most effective chiral selector
      in the enantioseparation of all the compounds, with high resolution values. A
      HPLC method, using immobilised serum protein columns, human serum albumin (HSA)
      and alpha1-acid glycoprotein (AGP), was also investigated. Two benzodioxane
      racemates were well resolved on a mixed tpe (50% HSA and 50% AGP) column, with
      enantioselective binding on AGP column.

PMID- 9634280
TI  - [Lamellar bodies in the amniotic fluid--a rapid and accessible test of fetal lung
      maturity].

PMID- 9634282
TI  - [Reports from the Czech Gynecology and Obstetrical Society Congress held 20-23
      March 1997 in Carlsbad].

PMID- 9634281
TI  - [Proceedings of the Congress of the Czech Society of Gynecology. Karlovy Vary, 20
      23 March 1997].

PMID- 9634283
TI  - [Family planning and the law].

PMID- 9634285
TI  - [Does hyperoxia affect defensive reflex mechanisms in the respiratory tract?].

PMID- 9634286
TI  - [Respiratory tract reflexes after diagnosis and therapy of sleep apnea].

PMID- 9634287
TI  - [Noninvasive evaluation of anthracycline cardiotoxicity].

PMID- 9634288
TI  - [Signal-averaged electrocardiography as part of comprehensive care of heart
      transplant patients].

PMID- 9634289
TI  - Adolescent sexual behaviour: results from an Ontario sample. Part 1: Adolescent
      sexual activity.
AB  - In spite of a variety of broad-based interventions, rates of adolescent sexual
      intercourse remain high. Using data from a large longitudinal study, this paper
      provides empirical evidence of Canadian adolescent sexual activity rates by age
      and gender. The incidence of first sexual intercourse among those 13-15 years was
      higher among males than females; by ages 16-17 years, rates were the same for
      both genders (25%). Prevalence of sexual intercourse with age; by age 16-17
      years, similar rates were reported for both genders (approximately 50%). Analysis
      of data over a three-year period indicated that at each age, over 80% of
      adolescents reported intermittent or no sexual intercourse. Different factors
      predicted the absence of early sexual intercourse for the two genders. These data
      provide useful information about Canadian adolescent sexual activity,
      particularly related to identifying high risk groups for targeted prevention
      interventions.

PMID- 9634291
TI  - [Evaluation of the efficiency and safety of the loratadine with pseudoephedrine
      combination drug in treatment of seasonal allergic rhinitis].
AB  - The aim of the study was to assess efficacy and safety of 5 mg loratadine/120 mg
      pseudoephedrine combination drug in patients with seasonal allergic rhinitis. 30
      patients allergic to grass pollen were treated with the new drug (Clarinase)
      twice a day in 15-day study during grass pollen seasonal. Nasal an non-nasal
      symptoms were evaluated for efficacy. Loratadine/pseudoephedrine combination
      effected a significant decrease in total symptoms score as well as individual
      evaluated symptoms score: nasal stuffiness, itching and discharge, sneezing, eye
      itching, tearing and redness of the eyes. The treatments was well tolerated. No
      serious side effects were noticed. The incidence of mild sedation, dry mouth,
      insomnia and nervousness was only 3 to 7 percent. 5 mg loratadine plus 120 mg
      pseudoephedrine was safe and effective in relieving the symptoms of allergic
      rhinitis.

PMID- 9634292
TI  - [Abstracts of work presented at the 47th Pharmacology Seminar in Kosice (3-5
      September 1997)].

PMID- 9634293
TI  - Can HSV latency be conquered by current antiviral therapies?

PMID- 9634295
TI  - Race and ethnicity in STD analyses.

PMID- 9634296
TI  - Sexually transmitted diseases and the Raj.

PMID- 9634294
TI  - Influence of ovarian hormones on urogenital infection.
AB  - Numerous studies have examined the influence of hormones on infectious diseases
      and there is now a wealth of data relating to the more specific effect of the sex
      hormones, oestrogen and progesterone, on urogenital infections. The interaction
      between these hormones and the immune system is complex and the variation of
      hormonal effect between species further complicates the true picture as related
      to humans. Although it is difficult therefore to draw general conclusions
      regarding predominant effects of specific hormones, there is the suggestion that
      oestrogen enhances the pathogenicity of many urogenital micro-organisms. Our
      understanding of the influential role played by sex hormones in disease
      pathogenesis is at an early stage and illustrates well the importance of drawing
      together and interpreting as a whole both epidemiological and molecular studies.

PMID- 9634297
TI  - Association of Kaposi's sarcoma associated herpesvirus (KSHV) DNA in
      bronchoalveolar lavage fluid of HIV infected individuals with bronchoscopically
      diagnosed tracheobronchial Kaposi's sarcoma.
AB  - OBJECTIVES: To determine the frequency of detection of Kaposi's sarcoma
      associated herpesvirus (KSHV), also known as human herpesvirus (HHV) type 8, DNA
      in bronchoalveolar lavage (BAL) fluid from HIV infected individuals with and
      without KS and to compare this with the detection rate in peripheral blood. Also
      to identify whether KSHV was associated with specific cell types in lavage fluid.
      METHODS: Nested PCR was used to detect KSHV DNA in BAL fluid from 41 consecutive
      individuals with Kaposi's sarcoma (KS) and in 41 controls with similar CD4
      lymphocyte counts. Semiquantification of viral DNA was by end point titration. A
      positive cell sorting selection procedure was used to isolate specific BAL fluid
      cell types. RESULTS: KSHV DNA was detected in BAL fluid from 24 of 29 (83%)
      individuals with a bronchoscopic diagnosis of tracheobronchial KS. None was
      detected in 12 individuals with only cutaneous KS, or in 41 matched controls
      without KS. In five, KSHV DNA was detected in the cell depleted and cellular
      fractions of BAL fluid and in 1/5 in the CD14 (macrophage) fractions. None was
      detected in the CD19 (B lymphocyte) or CD4/CD8 (T lymphocyte) fractions.
      CONCLUSIONS: There was a clear association between the diagnosis of
      tracheobronchial KS and detection of KSHV DNA in BAL fluid. The cell type
      supporting KSHV in the respiratory tract is not CD 19 positive and has yet to be
      conclusively identified.

PMID- 9634298
TI  - Comparison of clinical, histological, and virological symptoms of HPV in HIV-1
      infected men and immunocompetent subjects.
AB  - OBJECTIVE: We assessed the clinical, histological, and virological features of
      anogenital human papillomavirus (HPV) infection, according to their immune status
      in HIV-1 infected men, referred for an anogenital examination or treatment, in
      comparison with immunocompetent patients. METHODS: The study population comprised
      33 HIV-1 infected heterosexual or homosexual men and 38 HIV negative men seen in
      a screening and treatment centre for anogenital HPV infections. All patients were
      examined with a colposcope. Biopsies were carried out on all subjects with
      anogenital lesions for histological studies and HPV detection by Southern blot.
      RESULTS: The HIV infected patients had a balanopreputial HPV infection in 70%,
      anal in 30%, and urethral in 37%, while HIV negative patients had balanopreputial
      lesion in 72%, anal in 26%, and urethral in 16%. Diffuse anogenital lesions were
      present in 33% of the HIV infected cases and in 10.5% of HIV negative cases (p <
      0.02). Among the HIV infected patients, the genital HPV lesions were
      condylomatous in 67.5% of the cases and dysplastic in 57%. HIV negative patients
      had condylomatous lesions in 86% of the cases and dysplasic in 14%. The
      condylomatous lesions of HIV infected patients had a low grade malignant
      histological aspect in 36% of the cases and high grade histological criteria were
      found in 22% of the dysplasias. Oncogenic HPVs were detected more frequently in
      HIV infected patients (35% v 12%) and more than one HPV type was found in 21.5%
      of cases. Neither the anogenital diffusion of the HPV lesions nor their
      morphological, histological, and virological features differed significantly in
      patient with CD4 cell counts > or < 200 x 10(6)/l. In contrast, patients with CD4
      cell counts < 50 x 10(6)/l had a higher risk of several types of HPVs and of
      developing a diffuse anogenital infection. CONCLUSION: HIV-1 infected patients
      had an increased frequency of high grade anogenital dysplastic lesions and a
      higher frequency of HPV infection with multiple and diffuse sites of involvement.
      These characteristics of HPV infection were independent of the patients' immune
      status up to CD4 cell counts > 50 x 10(6)/l but showed an increased risk when the
      CD4 cell count was < 50 x 10(6)/l. The higher frequency of diffuse anogenital
      infections among HIV infected men calls for rapid treatment, laser or surgery,
      given the association of histological features of intraepithelial neoplasia and
      the presence of multiple HPV infection sites which may be the consequence of
      immune disturbances, most of which are transmissible potentially oncogenic HPVs.

PMID- 9634300
TI  - Moving towards a Cochrane review group in sexually transmitted diseases.

PMID- 9634299
TI  - Clinical algorithms for the screening of pregnant women for STDs in Libreville,
      Gabon: which alternatives?
AB  - OBJECTIVE: Sexually transmitted diseases (STDs) remain one of the major public
      health problems in the developing world. To implement a systematic screening of
      STDs among pregnant women in Libreville, Gabon, a preliminary cross sectional
      study on STD prevalence and risk factors was performed in antenatal clinics. A
      score, integrating risk factors and elementary clinical signs for the screening
      of STDs, showed higher performances compared with hierarchical algorithms. The
      prospective validation of this score based on six criteria (risk factors and
      simple clinical signs) was done in 1994-5. The sensitivity (76.7%), compared with
      results from other studies, was acceptable for diagnosing cervical infection
      (Neisseria gonorrhoeae and/or Chlamydia trachomatis) but the specificity was low
      (50.6%). In addition, the diagnostic values for diagnosing vaginal infection
      (Trichomonas vaginalis and/or Candida albicans) were poor. We then proposed to
      evaluate an alternative flowchart for the screening of cervical and vaginal
      infections. METHODS: In this study, 646 pregnant women were enrolled. Each woman
      was interviewed and examined by a physician and then was subjected to reference
      laboratory examinations. An algorithm in two steps, combining a risk assessment
      score at the beginning of a hierarchical process, followed by a second step more
      specifically applied to a limited number of women, was developed and evaluated.
      RESULTS: The prevalence rate was 11.3% for cervical infection and 39.5% for
      vaginal infection. The first step of the algorithm, applied to all pregnant
      women, is based on four criteria (age, marital status, dyspareunia, coloured
      vaginal discharge). It allows classification of the women into three classes:
      high, low, and intermediate risk of cervical infection. Only the patients with
      intermediate risk were submitted to further investigations including speculum and
      microscopic examination, and subsequently chlamydial antigen detection. This
      flowchart was 83.6% and 81.2% sensitive and 63.4% and 62.7% specific for
      predicting cervical infection and vaginal infection, respectively. CONCLUSION:
      Similar strategies using simple rapid tests for chlamydial and gonococcal
      infection would certainly constitute a good diagnostic tool. This theoretical
      model needs to be evaluated prospectively, not only to confirm their diagnostic
      value but also to evaluate their feasibility, reliability and acceptability, as
      well as their cost effectiveness.

PMID- 9634301
TI  - More transparency, greater depth.

PMID- 9634302
TI  - Racial origin, sexual behaviour, and genital infection among heterosexual men
      attending a genitourinary medicine clinic in London (1993-4).
AB  - OBJECTIVES: To compare variables of sexual behaviour and incidence of genital
      infections among heterosexual men of different racial origins. DESIGN: A
      prospective cross sectional study of sexual behaviour reported by a standardised
      self administered questionnaire in new patients who presented for screening and
      diagnosis. SETTING: A genitourinary medicine clinic in west London. SUBJECTS:
      1212 consecutive heterosexual men newly attending in 1993-4. MAIN OUTCOME
      MEASURES: Variables relating to sociodemographic status, sexual behaviour, condom
      use, sexually transmitted diseases, and other genital infections stratified by
      racial origin. RESULTS: There were 941 evaluable heterosexual men of whom the
      majority were white (79%) and 17% were black. The black men comprised more
      teenagers (11% cf 2%; p < 0.00001), were more likely to be unemployed (26% cf
      12%; p < 0.00001), to have commenced intercourse much earlier (45% cf 22% before
      aged 16: p < 0.0001), and to have had intercourse with an African woman (14% cf
      6%; p < 0.001). Both fellatio (64% cf 96%; p < 0.00001) and cunnilingus (40% cf
      92%; p < 0.00001) were practised less frequently by the black men and so too was
      anal intercourse (11% cf 27%; p < 0.00001). Similar proportions from both groups
      were non-smokers (53% cf 57%), but a significantly higher proportion of the black
      men did not drink alcohol (13% cf 5%; p < 0.001). Gonorrhoea (15% cf 1%; p <
      0.00001), chlamydial infection (17% cf 8%; p < 0.001), and non-gonococcal
      urethritis (37% cf 24%; p = 0.001) were diagnosed more frequently in the black
      men. These findings remained significant after logistic regression and are
      therefore independently associated with black race. However, there was no
      significant difference in numbers of sexual partners in the preceding year
      (median 2), nor in condom use with regular and non-regular partners. The Asian
      men had commenced intercourse later (mean 19.1 years) than both the black men
      (mean 15.9 years) and the white men (mean 17.3 years). CONCLUSIONS: Compared with
      white men, black men attending a genitourinary medicine clinic were much more
      likely to be unemployed, to have commenced intercourse earlier and to have
      urethral infection. They were much less likely to practice fellatio, cunnilingus,
      or anal intercourse. However, there was no difference between the two racial
      groups in respect of numbers of sexual partners and condom use.

PMID- 9634303
TI  - Racial origin, sexual lifestyle, and genital infection among women attending a
      genitourinary medicine clinic in London (1992).
AB  - OBJECTIVES: To compare variables of sexual behaviour and incidence of genital
      infections among women of different racial origins and lifestyles. DESIGN: A
      prospective cross sectional study of sexual behaviour reported by a standardised
      self administered questionnaire in new patients who presented for screening and
      diagnosis. SETTING: A genitourinary medicine clinic in west London. SUBJECTS:
      1084 consecutive women newly attending in 1992. MAIN OUTCOME MEASURES: Variables
      relating to sociodemographic status, sexual lifestyle, condom use, sexually
      transmitted diseases, and other genital infections stratified by racial origin.
      RESULTS: There were 948 evaluable women, of whom 932 (98.3%) were heterosexual
      and 16 (1.7%) were lesbian. Previous heterosexual intercourse was reported by 69%
      of lesbian women and their most frequent diagnosis was bacterial vaginosis (38%).
      The majority of heterosexual women were white (78%) and 16% were black. The black
      women were more likely to be teenagers (18% cf 8%; p = 0.0004) or students (28%
      cf 15%; p = 0.0008), and to have had an earlier coitarche (48% cf 38% before aged
      17; p < 0.004). They also had a higher proportion of pregnancies (58% cf 38%; p <
      0.00001) and births (38% cf 20%; p < 0.00001). The white women showed
      significantly more sexual partners during the preceding year (p = 0.004) and in
      total (p < 0.00001) and more reported non-regular partners (48% cf 35%; p =
      0.004) with whom they were more likely to use condoms (p = 0.009). However, the
      black women were more likely to have gonorrhoea (7% cf 2% p < 0.0003), chlamydial
      infection (12% cf 5% p < 0.002), trichomoniasis (10% cf 2% p < 0.00001), or to
      sexual contacts of men with non-gonococcal urethritis (19% cf 12% p < 0.02). They
      were less likely to have genital warts (3% cf 12% p = 0.002). Logistic regression
      showed that all these variables were independently associated with the black
      women. The Asian women (2%), none of whom had a sexually transmitted disease, had
      commenced intercourse later (mean 19.7 years) than both black women (mean 16.8
      years) and white women (mean 17.6 years). CONCLUSIONS: Sexual intercourse
      commenced approximately 1 year earlier in the black women, who were more likely
      to have become pregnant, had children, and to have acquired a bacterial sexually
      transmitted infection than were the white women.

PMID- 9634304
TI  - HIV infection among family planning clinic attenders in Glasgow: why prevalence
      has remained low in this general population group.
AB  - OBJECTIVE: During 1991-2, unlinked anonymous testing of dried blood spots from
      neonatal metabolic screening cards showed the prevalence of HIV among
      childbearing women from Glasgow to be extremely low at 0.01%. A study was
      conducted to determine if non-pregnant sexually active women who engaged in
      unprotected sexual intercourse were more likely to be infected than those who
      were pregnant. METHODS: Unlinked anonymous HIV testing of urine specimens
      submitted by attenders of the family planning clinic in Glasgow for pregnancy
      testing. RESULTS: Of 11,990 urine specimens tested, 7664 were from women with a
      negative pregnancy test and two of these were HIV positive (0.026%); none of the
      remainder from those with a positive pregnancy test had HIV antibodies.
      CONCLUSION: No hidden epidemic was unearthed among a population which had engaged
      in unprotected sexual intercourse and was not pregnant. Other data from Glasgow
      strongly suggest that the control of HIV transmission among the city's population
      of current injectors (HIV prevalence, 1% of 8500) has prevented the spread of
      infection into its wider heterosexual population. It is essential that preventive
      measures which have been responsible for this public health success should be
      maintained.

PMID- 9634305
TI  - Evaluation of a targeted HIV prevention programme among female commercial sex
      workers in the south of Thailand.
AB  - OBJECTIVE: To evaluate a targeted HIV prevention programme among female
      commercial sex workers (CSWs) in the south of Thailand. SUBJECTS AND METHODS: A
      pretest-post-test comparison group study was carried out in Sungai Kolok and
      Betong between June and December 1994. In June 408 CSWs were entered in Sungai
      Kolok (the intervention area) and 343 CSWs were enrolled in Betong (the
      comparison area). In December 1994, 416 women were enrolled in Sungai Kolok and
      342 in Betong. Of these women 37% (n = 283) also participated in the June survey.
      All women completed an oral interview and blood samples were collected for HIV
      serology. The intervention programme consisted of an informational and
      educational campaign and peer educator training. RESULTS: Increase in knowledge
      and perceived vulnerability was more pronounced in the intervention area but did
      not translate into a greater increase in condom use. Refusal of customers
      unwilling to use a condom and manager support in doing so were the only factors
      independently related to positive changes in condom use. HIV prevalence
      (approximately 20%) and incidence (approximately 4.2 per 100 women years) were
      the same in both study locations. Women in the intervention area reported
      significantly fewer customers and income from sex work, possibly as a result of a
      coincidental police campaign to suppress (child) prostitution. CONCLUSIONS: HIV
      incidence among CSWs in the south of Thailand is still high. Prevention
      programmes should focus on improvement of negotiation and refusal skills and
      manager support in using condoms.

PMID- 9634306
TI  - Analysis of quinolone resistance mechanisms in Neisseria gonorrhoeae isolates in
      vitro.
AB  - BACKGROUND AND OBJECTIVES: Gonococcal fluoroquinolone resistance is now a
      significant problem in Japan. We generated gonococcal mutants resistant to
      norfloxacin in vitro from norfloxacin sensitive isolates and analysed the
      contribution of three known mechanisms of quinolone resistance in Neisseria
      gonorrhoeae. MATERIALS AND METHODS: Three clinical isolates of N gonorrhoeae
      susceptible to norfloxacin were exposed to increasing concentrations of
      norfloxacin. To identify mutations in the gyrA and parC genes of the gonococcal
      mutants, the quinolone resistance determining regions of the gyrA and parC genes
      were polymerase chain reaction (PCR) amplified and the PCR products were directly
      sequenced. Norfloxacin accumulation in the gonococcal cells was also measured.
      RESULTS: The MICs of norfloxacin for three variants containing a single GyrA
      mutation were 16-fold higher than that for their parent isolates. A variant
      showing reduced norfloxacin accumulation in the cells, without mutations in the
      GyrA or ParC proteins, was also less sensitive to norfloxacin, with a 16-fold
      increase in the MIC, compared with the parent strain. The MIC of norfloxacin for
      a variant which contained a single GyrA mutation with reduced norfloxacin
      accumulation in the cells was 128-fold higher than for the parent strain. A
      variant containing mutations in both GyrA and ParC proteins with reduced
      accumulation of norfloxacin in the cells showed a 256-fold increase in the
      norfloxacin MIC compared with the parent strain. There was no variant containing
      a ParC mutation without the simultaneous presence of a GyrA mutation.
      CONCLUSIONS: The results from this study suggest that not only a mutation in the
      gyrA gene but also reduced drug accumulation in cells contributes to the
      development of fluoroquinolone a mutation in the gyrA gene contributes to a high
      level of fluoroquinolone resistance in gonococci with decreases in accumulation
      in cells having an additional but lesser effect.

PMID- 9634307
TI  - Oral sex and the transmission of viral STIs.
AB  - OBJECTIVE: To review the literature on the role of oral sex in the transmission
      of viral sexually transmitted infections (STIs). METHOD: A Medline search was
      performed using the keywords oro-genital sex, and those specific to each
      infection. Further references from each article identified by Medline were also
      included, as were relevant references from "Current contents". CONCLUSIONS: Oral
      sex is a common sexual practice among both heterosexual and homosexual couples.
      The evidence suggests that HIV transmission can take place through oro-genital
      sex from penis to mouth and vagina to mouth. Case reports describe apparent
      transmission from mouth to penis although this appears less likely. The risk of
      oro-genital transmission of HIV is substantially less than from vaginal and anal
      intercourse. Receptive oro-genital sex carries a small risk of human
      papillomavirus infection and possibly hepatitis C, while insertive oro-genital
      contact is an important risk factor for acquisition of HSV 1. Oro-anal
      transmission can occur with hepatitis A and B. The transmission of other viruses
      may occur but is unproved. The relative importance of oral sex as a route for the
      transmission of viruses is likely to increase as other, higher risk sexual
      practices are avoided for fear of acquiring HIV infection.

PMID- 9634308
TI  - Polymerase chain reaction detection of Haemophilus ducreyi DNA.
AB  - OBJECTIVES: To develop a polymerase chain reaction (PCR) method to detect
      Haemophilus ducreyi DNA in cultured isolates and clinical material. METHODS:
      Primers specific to the H ducreyi 16s rRNA gene were synthesised. PCR conditions
      were optimised and products were verified by restriction endonuclease digestion
      and agarose gel electrophoresis. RESULTS: The method was able to detect all 28 H
      ducreyi strains tested; specificity was demonstrated using lysates of 12 related
      organisms. Applied to clinical samples from genital ulcer swabs obtained in
      Harare, Zimbabwe, H ducreyi DNA was detected in repeated assays in 35 clinical
      samples. CONCLUSION: PCR amplification using primers from the 16s rRNA gene may
      be a useful alternative to culture for the detection of H ducreyi and the
      diagnosis of chancroid.

PMID- 9634310
TI  - Sixth European Conference on Clinical Aspects and Treatment of HIV Infection,
      Hamburg, Germany, 11-15 October 1997.

PMID- 9634309
TI  - Pooling of urine specimens for PCR testing: a cost saving strategy for Chlamydia
      trachomatis control programmes.
AB  - OBJECTIVES: To evaluate pooling of first catch urine (FCU) specimens as a cost
      effective strategy for chlamydia testing. METHODS: Mock specimens were pooled
      with and without dilution to determine optimal pool size and ease of work flow.
      The performance of the Amplicor Chlamydia trachomatis PCR assay on pooled
      specimens was compared with individual testing using 370 FCU specimens from
      asymptomatic men presenting to an STD clinic. Cost savings associated with
      pooling were estimated. RESULTS: Using mock specimens, the sensitivity and
      specificity of the Amplicor PCR assay were not affected by pool sizes of two and
      five, but at a pool size of 10 decreased sensitivity due to inhibition was
      observed in one of five mock pools when the pooling method which involved no
      dilution was used. Archived FCU specimens from a study of 370 asymptomatic men
      were combined consecutively into 74 pools of five and tested by PCR. Of the 18
      pools that contained positive specimens, 17 were PCR positive. Compared with
      testing FCU specimens individually, pooling resulted in a sensitivity of 95%,
      specificity of 100%, and a cost savings of 57% based on reduced number of tests
      required. CONCLUSION: Depending on the prevalence of infection, pooling of FCU
      specimens for PCR testing may result in cost savings compared with testing
      specimens individually. Further evaluations to validate this strategy using fresh
      FCU specimens are needed.

PMID- 9634311
TI  - International Congress of Sexually Transmitted Diseases, 19-22 October 1997.

PMID- 9634312
TI  - Age and sexual risk behaviour.

PMID- 9634313
TI  - Severe hyponatraemia and severe hyperkalaemia in an HIV positive patient who
      received high dose co-trimoxazole.

PMID- 9634314
TI  - Visualisation and quantification of HIV related brain atrophy using registered
      serial magnetic resonance imaging.

PMID- 9634315
TI  - Do junior doctors know what to do if they have a needlestick injury?

PMID- 9634316
TI  - Second generation heterosexual transmission of HIV-1 infection from women
      infected in the United Kingdom.

PMID- 9634317
TI  - Acceptability of clinics for sexually transmitted diseases among users of the
      "gay scene" in the West Midlands.

PMID- 9634318
TI  - Microbiological diagnosis of gonorrhoea.

PMID- 9634319
TI  - Sample size and diagnostic test evaluations.

PMID- 9634320
TI  - Azithromycin for the treatment of donovanosis.

PMID- 9634322
TI  - Hepatitis B virus infection in patients attending a genitourinary medicine
      clinic: risk factors and vaccine coverage.
AB  - BACKGROUND: The hepatitis B virus (HBV) immunisation policy in the United Kingdom
      includes offering vaccines selectively to those at risk by sexual contact. Among
      genitourinary medicine (GUM) clinic attenders, homosexual men are offered
      vaccine, but estimates of the vaccine uptake are required to monitor policy and
      estimate the possible impact on transmission; heterosexuals are not routinely
      offered vaccine, but this policy might change if the prevalence was found to be
      high. OBJECTIVE: To determine the prevalence of HBV infection and vaccine uptake
      among patients attending a GUM clinic. METHODS: HBV seroprevalence determined by
      unlinked anonymous testing of consecutive blood samples sent for syphilis
      serology. Demographic and risk factor data and history of HBV immunization
      extracted from clinic notes before unlinking. Prevalence data were compared with
      a population of first time blood donors from the same area. SETTING: Open access
      GUM clinic in central London. RESULTS: Samples were obtained and tested from 441
      homosexual and 527 heterosexual men and from 821 women over a 4 month period in
      1990. After exclusion of injecting drug users and their sexual partners (n = 30)
      and HBV carriers attending for follow up (n = 12), the prevalence of antibody to
      HBV core (anti-HBc) was 38.7% in homosexual men, 5.9% in heterosexual men, and
      3.5% in women (50.0%, 6.0%, 3.7% respectively if previous vaccinees were also
      excluded). The prevalence of HBV surface antigen positivity was 4.2%, 0.60%, and
      0.39% respectively after exclusion of vaccinees (chi(2) p < 0.001 for homosexual
      men versus others). The prevalence of the anti-HBc in first time blood donors was
      1.1% (8/749). Among male GUM clinic attenders, the prevalence of anti-HBc was
      higher in those of non-UK origin or place of birth and/or non-white ethnicity
      (odds ratios 2.87, 95% CI 1.57-5.24 and 8.06, CI 3.39-19.1, in homosexuals and
      heterosexuals respectively). In homosexual men anti-HBc prevalence increased with
      age (OR 1.05, CI 1.02-1.07 for each year) and lifetime number of STDs (OR 6.36,
      CI 3.77-10.8 for > or = 2 versus < 2) and in clinic reattenders compared with new
      patients (OR 5.42, 95% CI 3.32-9.16). Among heterosexuals, age was associated
      with anti-HBc prevalence in women (OR 1.09, CI 1.04-1.12) but not men (OR 0.99,
      95% CI 0.95-1.02). There were no other associations in heterosexuals. A history
      of HBV immunisation in homosexual men was recorded in 13/131 (9.9%) of new
      patients and 103/305 (33.8%; OR 4.63, CI 2.49-8.60) clinic reattenders.
      CONCLUSIONS: Although higher than a sample of blood donors, the prevalence of
      serological markers of HBV infection among heterosexuals was low, providing
      little support for extending HBV immunisation to all heterosexuals attending GUM
      clinics as a targeted strategy for control of HBV infection. Homosexual men
      remain at high risk of infection, but many are now being immunised. Efforts to
      improve compliance with existing vaccine policies in GUM clinics should be
      encouraged.

PMID- 9634323
TI  - A randomized controlled trial comparing nonoxynol-9 lubricated condoms with
      silicone lubricated condoms for prophylaxis.
AB  - OBJECTIVE: We tested the effect of nonoxynol-9 (N-9) in condom lubrication on the
      risk of acquiring STD and genital discomfort. METHODS: The study was a triple
      masked, randomised controlled trial comparing N-9 lubricated condoms with plain
      silicone lubricated condoms among Dominican female sex workers. RESULTS:
      Randomisation provided two groups (313 for N-9 and 322 for plain) similar in
      baseline characteristics, but extensive loss to follow up occurred (56 women in
      each group completed the 24 week follow up). Most vaginal acts with clients were
      protected with condoms (99% of vaginal sex) but fewer acts with non-clients were
      protected (43% of vaginal sex). No significant differences occurred in rates of
      cervical infections (N-9 = 3.4 per 100 person months v plain = 2.8),
      trichomoniasis (N-9 = 2.8 v plain = 3.6), or discomfort rates (N-9 = 0.82 v plain
      = 0.92). CONCLUSIONS: Plain silicone lubricated condoms are as effective as N-9
      lubricated condoms, cost less, have longer expected shelf life, and therefore may
      be the better condom to provide.

PMID- 9634324
TI  - Community based study of sexually transmitted diseases in rural women in the
      highlands of Papua New Guinea: prevalence and risk factors.
AB  - OBJECTIVE: To estimate the prevalence of sexually transmitted diseases (STDs) and
      determine their risk factors/markers among a rural population of women in the
      highlands of Papua New Guinea. METHODS: Community based random cluster sample of
      women of reproductive age were interviewed and examined and had specimens
      collected for laboratory confirmation of chlamydial and trichomonal infection,
      gonorrhoea, syphilis, and bacterial vaginosis. RESULTS: Chlamydia trachomatis was
      detected in 26%, Trichomonas vaginalis in 46%, Neisseria gonorrhoeae in 1%,
      syphilis in 4%, pelvic inflammatory disease (PID) (diagnosed clinically) in 14%,
      and bacterial vaginosis in 9% of 201 women. 59% of the women had at least one
      STD. In a multivariate logistic regression analysis taking the clustered sampling
      into account, independent risk factors for chlamydial infection were age < or =
      25 years, < four living children, visualization of yellow mucopurulent
      endocervical secretions on a white swab, and bacterial vaginosis. Being married
      to a man who did not have other wives was protective. For trichomonal infection,
      independent risk factors were having no formal education, infertility, more than
      one sexual partner in the previous 12 months, treatment for genital complaints in
      the previous 3 months, abnormal vaginal discharge detected on examination, and
      chlamydial infection. Similar levels of trichomonal infection were found in all
      age groups. Among married women, rates of infection correlated with their
      perception of their husband having had other sexual partners in the previous 3
      months, and this relationship was significant for chlamydial infection among
      women over 25. CONCLUSION: STDs are a major problem in this population, with the
      risk factors varying by outcome. Current treatment regimens are inappropriate
      given the high prevalence of trichomonal infection, and the available services
      are inadequate. Effective interventions are required urgently to reduce this
      burden and to prevent the rapid transmission of HIV.

PMID- 9634321
TI  - Molecular events in uterine cervical cancer.
AB  - OBJECTIVE: To review the literature regarding the molecular events which occur in
      the development of uterine cervical cancer, with particular reference to human
      papillomavirus (HPV) infection. METHODOLOGY: Bibliographic searches of Medline
      and the ISI citation databases using appropriate keywords, including the
      following: papillomavirus, cervix, pathology, cyclin, chromosome, heterozygosity,
      telomerase, smoking, hormones, HLA, immune response, HIV, HSV, EBV. CONCLUSIONS:
      It has become clear that most cervical neoplasia, whether intraepithelial or
      invasive, is attributable in part to HPV infection. However, HPV infection alone
      is not sufficient, and, in a small proportion of cases, may not be necessary for
      malignant transformation. There is increasing evidence that HPV gene products
      interfere with cell cycle control leading to secondary accumulation of small and
      large scale genetic abnormalities. This may explain the association of viral
      persistence with lesion progression but, in many patients, secondary factors,
      such as smoking and immune response, are clearly important. However, the
      mechanisms involved in the interaction between HPV and host factors are poorly
      understood.

PMID- 9634325
TI  - HIV infection and high risk behavior among patients attending an STD referral
      clinic in Prague, Czech Republic.
AB  - OBJECTIVE: This survey was conducted to determine the prevalence of HIV infection
      and associated risk behaviour in a high risk population of clients attending an
      STD clinic in Prague, Czech Republic. METHODS: Between September 1994 and January
      1995, clients entering the Apolinar STD clinic in Prague, Czech Republic, were
      enrolled in a blinded, unlinked HIV antibody seroprevalence study. Non
      identifying demographic characteristics, STD diagnoses, HIV risk exposures, and
      voluntary HIV testing experience were extracted from medical charts. RESULTS: Of
      1394 patients for whom serum was available for testing, one was positive for HIV
      (HIV prevalence 0.07%, 95% confidence interval (CI) 0.01, 0.41%). This person was
      one of 28 men having sex with men (MSWM) (HIV prevalence among MSWM 3.6%, 95% CI
      0.6, 17.7%). Among the 775 male clients, 75.5% had heterosexual unprotected sex,
      11.1% had sex with high risk partners or prostitutes, 3.6% were MSWM, 1.0% were
      injecting drug users (IDUs), 0.7% were both MSWM and IDUs, and 6.8% and 1.8% had
      other or no recognized risk for HIV/STDs, respectively. Among the 619 female
      clients, 74.5% had heterosexual unprotected sex, 11.6% were prostitutes, 7.8% had
      sex with high risk partners, 1.1% were IDUs, and 3.9% and 2.3% had other or no
      recognised risk, respectively. The 304 adolescent patients (age 11-19 years)
      differed significantly (p < 0.05) in risk behaviour and STD diagnoses from the
      1090 patients who were 20 years and older. Adolescents were significantly more
      likely to be female (58.6% v 40.5%, OR = 2.1), IDUs (3.6% v 0.4%, OR = 10.2),
      prostitutes (8.9% v 4.7%, OR = 2.0), and have sex partners with STDs (7.6% v
      4.4%, OR = 1.8). The adolescent patients were also significantly more likely to
      be diagnosed with gonorrhoea (21.1% v 12.3%, OR = 1.9) and non-gonococcal
      urethritis (27.6% v 17.2%, OR = 1.8), and significantly less likely to have been
      tested previously for HIV (19.1% v 31.9%, OR = 0.5). CONCLUSIONS: HIV infection
      is currently uncommon in this population. However, the high rates of unprotected
      sex, prostitution, injecting drug use, and STDs, especially among adolescents,
      provide the basis for an epidemic in this population. Aggressive prevention
      education should be started before adolescence.

PMID- 9634326
TI  - Characteristics associated with prevalent HIV infection among a cohort of sex
      workers in Cameroon.
AB  - OBJECTIVE: To determine prevalence of HIV infection in a cohort of female sex
      workers in Cameroon, and to describe characteristics associated with HIV
      infection in this population. METHODS: In a cross sectional study, 2260 female
      sex workers in Cameroon were interviewed and screened for HIV serostatus. A
      standardised questionnaire was used to collect information on sociodemographic
      characteristics and sexual and health behaviours. RESULTS: Seropositive
      participants (18%) were more likely to be over age 25, have four or more
      children, live in Yaounde or Douala for 5 years or less, solicit clients in their
      homes or on the street, have a low educational level, earn a weekly income of
      less than $24, and have no other occupation outside of sex work. A logistic
      regression model of selected sociodemographic characteristics indicated that
      women at particularly high odds of HIV infection were older, poorer, and new
      immigrants to their city of residence. CONCLUSION: This seroprevalence study
      found a lower HIV prevalence than had been previously reported. Although our
      results are different, this group is still at much higher risk of HIV infection
      than the population as a whole.

PMID- 9634327
TI  - The tampon test for trichomoniasis: a comparison between conventional methods and
      a polymerase chain reaction for Trichomonas vaginalis in women.
AB  - OBJECTIVES: Trichomonas vaginalis is the most common STD worldwide and the
      infection has been linked with an increased risk of HIV transmission. We present
      a detailed comparison between conventional collection and testing methods and the
      polymerase chain reaction (PCR) tampon test for T vaginalis. METHODS: Women were
      tested for the presence of T vaginalis by PCR analysis of a tampon specimen and
      by conventional methods which included one or more of the following: culture and
      microscopy from a high vaginal swab (HVS) or endocervical swab (ECS), and
      microscopy of a Papanicolaou (Pap) smear. RESULTS: T vaginalis was detected in
      51/590 (8.6%) conventional tests and 93/590 (15.8%) tampon specimens. Retesting
      of all tampon PCR positive specimens confirmed 89/93 (95.7%) tests. Using the
      tampon PCR as the reference, the sensitivities of the different conventional
      sampling and testing methods for the detection of T vaginalis were 8.3% (5/60)
      for ECS microscopy or culture, 31% (13/42) for HVS microscopy or culture, 52.8%
      (19/36) for HVS directly inoculated into Trichomonas medium and 59.4% (38/64) for
      Pap smear. CONCLUSIONS: No conventional test in the remote setting has comparable
      sensitivity to PCR. The Pap smear is the next most sensitive, but requires a
      speculum examination. The use of PCR will allow inclusion of T vaginalis into STD
      screening programmes in both developed (lower prevalence) and developing (higher
      prevalence) countries.

PMID- 9634328
TI  - Sensitivity of the ligase chain reaction assay for detecting Chlamydia
      trachomatis in vaginal swabs from women who are infected at other sites.
AB  - OBJECTIVE: To assess the sensitivity of the ligase chain reaction (LCR) assay for
      Chlamydia trachomatis in vaginal swabs from women who were positive in cervical
      samples and/or urines. SUBJECTS: 413 women attending the genitourinary medicine
      clinic, St. Mary's Hospital, Paddington. METHODS: The LCR assay was used to test
      vaginal swabs from 46 women who were C trachomatis positive at one or both of the
      other sites by direct fluorescent antibody (DFA) staining, by an enzyme
      immunoassay (EIA), or by the LCR assay. RESULTS: The LCR assay of vaginal swabs
      had the following sensitivity values using confirmed positive results: 93%
      (41/44) compared with DFA staining of cervical deposits, 93% (41/44) compared
      with the LCR assay of cervical samples, 93% (28/30) compared with an EIA for
      cervical samples, 91% (39/43) compared with DFA staining of urine deposits, and
      93% (39/42) compared with the LCR assay of urine. Four women had vaginal swab
      samples negative by the LCR assay; one was positive only in the urine and two had
      cervical samples containing a small number of chlamydial elementary bodies.
      CONCLUSION: Testing vaginal swabs by the LCR assay is a sensitive method of
      detecting chlamydial infection; the results suggest that this procedure could be
      used as an alternative to examining urines in a screening programme for
      chlamydial infection in the community.

PMID- 9634329
TI  - Extragenital donovanosis in a patient with AIDS.
AB  - A case of extragenital donovanosis in a patient with AIDS is reported from
      Zimbabwe. Despite the rarity of donovanosis in Zimbabwe it is important that
      health workers are familiar with this disease since donovanosis increases the
      risk of HIV transmission and appropriate treatment is often successful even in
      patients with severe immunodeficiency.

PMID- 9634330
TI  - Should preventive antiretroviral treatment be offered following sexual exposure
      to HIV? The case for.

PMID- 9634331
TI  - Should preventive antiretroviral treatment be offered following sexual exposure
      to HIV? Not yet!

PMID- 9634332
TI  - Can we predict the prognosis of HIV infection? How to use the findings of a
      prospective study.

PMID- 9634333
TI  - A short history of the Medical Society for the Study of Venereal Diseases on its
      75th birthday. The Ninth Harrison Lecture.

PMID- 9634334
TI  - Relatively high risk of sexually transmitted and other genital diseases among
      women from Surinam and The Netherland's Antilles living in Amsterdam.

PMID- 9634336
TI  - Peer education and community based HIV prevention for homosexual men: peer led,
      evidence based, or fashion driven?

PMID- 9634335
TI  - Once weekly ganciclovir as prophylaxis is unacceptable to patients.

PMID- 9634337
TI  - Update of the CDC STD treatment guidelines: changes and policy.

PMID- 9634338
TI  - Guidelines for the management of herpes simplex virus infection in pregnancy.

PMID- 9634340
TI  - The evolution of veterinary surgical oncology.
AB  - Tremendous change and progress have occurred in the field of oncology over the
      last several decades. Progression in diagnostic techniques, patient support,
      adjuvant therapies and surgeon training has allowed the field of surgical
      oncology to make continued improvements in the human cancer field. Although a
      relatively young field, veterinary surgical oncology has followed in the
      progressive footsteps of our human counterparts. This article describes the
      evolution of this rapidly expanding field of veterinary medicine.

PMID- 9634339
TI  - Oral sex and transmission of non-viral STIs.
AB  - OBJECTIVES: To review the literature on the role of oral sex in the transmission
      of non-viral sexually transmitted infections (STIs). METHOD: A Medline search was
      performed using the keywords oro-genital sex, and those specific to each
      infection. Further references were then taken from each article read.
      CONCLUSIONS: Oral sex is a common sexual practice between both heterosexual and
      homosexual couples. Oro-genital sex is implicated as a route of transmission for
      gonorrhoea, syphilis, Chlamydia trachomatis, chancroid, and Neisseria
      meningitidis. Other respiratory organisms such as streptococci, Haemophilus
      influenzae, and Mycoplasma pneumoniae could also be transmitted by this route.
      Fellatio confers risk for acquisition of infection by the oral partner.
      Cunnilingus appears to predispose to recurrent vaginal candidiasis although the
      mechanism for this is unclear, while a link between oro-genital sex and bacterial
      vaginosis is currently being studied. Oro-anal sex is implicated in the
      transmission of various enteric infections. In view of the increased practice of
      oral sex this has become a more important potential route of transmission for
      oral, respiratory, and genital pathogens.

PMID- 9634341
TI  - Principles of tumor biopsy.
AB  - Tumor biopsy is the cornerstone of sound therapeutic decision making in oncology.
      Although there are multiple ways to obtain a biopsy from any given tumor, each
      individual procedure requires careful planning to ensure that the optimal
      treatment course is not compromised. Knowledge of the principles and techniques
      underlying biopsy is imperative to ensure an accurate diagnosis with minimal
      morbidity. This article describes the principles of biopsy and commonly used
      sampling techniques and where these procedures are most applicable. Appropriate
      tissue handling, interpretation of results, and some special techniques are also
      described.

PMID- 9634342
TI  - Preoperative patient planning and margin evaluation.
AB  - Preoperative assessment of the cancer patient can be broken down into: (1) What
      is it? (2) Where is it? and (3) What is the status of the patient? Evaluation of
      local disease begins with obtaining and interpreting cytologic or histologic
      (biopsy) samples. Tumor staging involves the assessment of tumor invasion into
      local tissues, draining lymph nodes, and distant sites, especially the pulmonary
      parenchyma. Staging is performed with the aid of imaging techniques and special
      procedures such as lymph node and bone marrow aspiration. Because many veterinary
      cancer patients are geriatric, examination of physiologic patient status through
      laboratory and other diagnostic avenues is vital to the appropriate selection and
      success of therapy. After these questions are answered, appropriate treatment
      options and an ultimate treatment plan can be formulated. This article describes
      logical and practical approaches for diagnosis, staging, patient assessment, and
      treatment planning of the animal presented with tumor disease. With appropriate
      preoperative assessment, we can offer our patients and clients the best care
      possible.

PMID- 9634343
TI  - Chemotherapy and the surgery patient: principles and recent advances.
AB  - Surgery is the mainstay of cancer therapy, yet there is mounting information
      demonstrating that chemotherapy is effective for the treatment of a wide variety
      of malignancies in dogs, cats and horses. Chemotherapy is not only being used to
      delay or eliminate metastatic disease, but also to enhance the local control of
      malignancies. New drugs and innovative combinations of chemotherapeutic agents
      are being evaluated at an ever increasing rate. Anticancer drugs are being
      delivered safer and more effectively because patients are being treated in new
      ways such as intralesionally or within body cavities. These agents are also being
      scheduled in more effective ways such as prior to, during, or after surgery.
      Techniques are being developed for drugs to be inhaled to reduce metastatic
      pulmonary disease. The purpose of this article is to review the general
      principals of cancer chemotherapy, the various toxicoses associated with these
      drugs, as well as examples of how chemotherapy has been used in combination with
      surgery.

PMID- 9634344
TI  - Principles of adjunctive radiation therapy.
AB  - Radiation therapy is becoming increasingly available to the practicing
      veterinarian. It is important that veterinarians be familiar with mechanisms and
      biologic effects of radiation used as a therapeutic modality in the treatment of
      cancer. It is also important that the veterinarian understand oncologic decision
      making and indications for various modalities including radiation therapy,
      surgery, and chemotherapy. Surgery and radiation therapy can be particularly
      complementary in combined therapy to achieve a functional and cosmetic result.
      This review introduces basic radiation therapy concepts, particularly regarding
      combination of radiation and surgery in the treatment of cancer in animals.

PMID- 9634345
TI  - Principles of oncologic orofacial surgery.
AB  - The most common orofacial tumors of dogs are malignant melanoma, squamous cell
      carcinoma, fibrosarcoma, osteosarcoma, and acanthomatous epulis. These tumors
      vary significantly in their metastatic potential, but are consistently locally
      invasive. Bone involvement is common, and complete excision often requires
      partial mandibulectomy or partial maxillectomy. Survival times after surgery are
      most strongly influenced by tumor type (or metastatic rate) and tumor location.
      Recent large retrospective studies have reported median survival times ranging
      from 4.6 to 26 months. The most common oral tumor of cats is squamous cell
      carcinoma. This is a highly invasive tumor that occasionally can be effectively
      treated with surgery alone, but that often requires a combination of surgery and
      radiation therapy.

PMID- 9634346
TI  - Tumor biology and pathology.
AB  - The correct pathologic diagnosis of tumor type affecting the veterinary patient
      is of utmost importance to the veterinary surgical oncologist. The surgical
      oncologist may be presented with benign or malignant diseases, and an accurate
      pathologic diagnosis may be necessary to distinguish between the two conditions.
      In either case, assessment of surgical margins to determine completeness of
      surgical removal is necessary. In cases of malignancy, the pathologist should
      grade the tumor, if appropriate, and be able to perform specialized techniques,
      such as immunohistochemistry, if a diagnosis is in question. The surgical
      oncologist needs to understand the principles of tissue collection, fixation, and
      submission to help the pathologist provide an accurate diagnosis. Finally, the
      oncologic surgeon and surgical pathologist need to establish a cooperative
      working relationship and function as a team to discuss difficult cases. This will
      ensure the best treatment for the veterinary patient.

PMID- 9634347
TI  - Principles of oncologic abdominal surgery.
AB  - The principles of abdominal oncologic surgery parallel the general principles of
      all types of oncologic surgery with some variations peculiar to the abdomen. Due
      to the presence of multiple organ systems within the abdominal cavity, many types
      of cancer can develop. The surgeon must be prepared to perform several different
      abdominal procedures depending on the organ system involved and the extent of the
      cancer. The surgeon as oncologist must be aware of the tumor type, its expected
      behavior, and current treatment options. This article describes the principles of
      performing cancer surgery, including preparation for abdominal exploration,
      methods to facilitate tumor removal, and ways of avoiding tumor recurrence.

PMID- 9634348
TI  - Thoracic surgical oncology.
AB  - Thoracic surgical oncology involves surgical treatment of lesions of the thoracic
      wall, pulmonary parenchyma, or mediastinum (also including heart, esophagus, or
      trachea). The most common neoplasms of the thoracic wall are osteosarcoma and
      chondrosarcoma. Histopathologic type, the use of chemotherapy for osteosarcoma,
      and completeness of surgical margins are prognostic for survival. Relative to
      solitary pulmonary masses, carcinomas are most common, with histopathologic type,
      tumor size, tumor grade, and lymph node status prognostic for survival. Of the
      aforementioned variables, lymph node status is the most significant. Extensive
      preoperative workup, including bronchoscopy and transthoracic fine needle
      aspiration of solitary lung masses, is usually not recommended. Thymomas are the
      most common surgical mediastinal mass. Patients are frequently affected with
      paraneoplastic syndromes including myasthenia gravis, polymyositis, and nonthymic
      neoplasia. Patients without megaesophagus with surgically resectable masses have
      an excellent prognosis for survival. Provision of analgesia after surgery in
      thoracotomy patients is extremely important. Carefully selected analgesic agents
      in thoracotomy patients are far less damaging to cardiovascular status than is
      tachycardia from excessive pain. Given these and other guidelines, perioperative
      mortality in thoracotomy patients is minimal, and long-term survival in selected
      patients is excellent.

PMID- 9634349
TI  - Surgery for skeletal sarcomas.
AB  - Skeletal neoplasms in pet animals are uncommon, but can represent a diagnostic
      and treatment challenge for the veterinary clinician. Osteosarcoma represents the
      most common histology of primary bone tumor and although the prognosis after
      treatment is still gaurded, major strides have been made in the treatment of this
      disease. Treatment success, however, requires a multidisciplinary approach.
      Additional histologic types cannot be ignored from the diagnosis of cases
      presenting as bone neoplasms, and many of these can have excellent long-term
      prognoses if treated appropriately. This article discusses the presentation,
      diagnosis, and treatment of skeletal neoplasms in general with a specific
      emphasis on osteosarcoma.

PMID- 9634350
TI  - Principles of treatment for soft tissue sarcoma.
AB  - Soft tissue sarcomas (STS) are mesenchymal tumors arising from connective tissue
      elements and are grouped together based on a common biologic behavior. The most
      common histologic types include malignant peripheral nerve sheath tumors
      (schwannoma and neurofibrosarcoma) "hemangiopericytoma," fibrosarcoma, and
      malignant fibrous histiocytoma. These tumors are relatively slow growing yet
      locally invasive with a high rate of recurrence following conservative
      management. Appropriate preoperative planning and aggressive surgical resection
      often result in long-term remission or cure. Identification and evaluation of
      resection margins are paramount in appropriate case management. The addition of
      radiotherapy after surgical resection can aid in remission for incompletely
      resected masses. Systemic chemotherapy for STS should be considered for high
      grade tumors with a moderate metastatic potential. Potential prognostic factors
      include grade, resection margins, size, location, histologic type, and previous
      treatment, with grade and margins being the most important. Tumor types
      classified as STS that differ slightly in their presentation or treatment,
      including synovial cell sarcoma, rhabdomyosarcoma, liposarcoma, and vaccine
      associated STS in cats, are discussed. Soft tissue sarcomas can be a frustrating
      disease to treat, but adherence to solid surgical oncology principles can greatly
      increase the odds of good disease control.

PMID- 9634351
TI  - Principles of surgery for cancer palliation and treatment of metastases.
AB  - Surgery in animals for palliation of clinical signs and treatment of cancer
      metastases is becoming more popular. Patients must be selected carefully and
      clear treatment goals established to maximize efficacy and minimize treatment
      related morbidity and mortality. Palliative treatment is rendered primarily to
      control clinical signs and secondarily to prolong life. Ironically,
      metastasectomy is often performed with the intent to cure. For both
      considerations, the clinician must be knowledgeable of the natural history of the
      affecting neoplasia (i.e., how will the patient fare without treatment) and the
      success rates and expected complications of the surgical procedures being
      considered. Clinical guidelines for patient selection are presented and discussed
      for palliative treatment and metastasectomy. Although data are available in the
      human and veterinary medical literature to aid decision making, sound clinical
      judgment remains most important for proper patient selection and care.

PMID- 9634352
TI  - Principles of reconstructive surgery for the tumor patient.
AB  - Small animal oncologic surgery is a relatively new and rapidly expanding field of
      veterinary science. Many exciting and innovative techniques for surgical
      resection of invasive tumors have been developed and published in the last
      decade. Paralleling these developments have been major advancements in the
      frontiers of reconstructive options to close the defects after major ablative
      surgery. A more thorough understanding of the biologic behavior of tumors in our
      patients has permitted us to rationally approach selected patients with high
      doses of surgery with curative intent, palliation, or as part of a multimodality
      treatment plan. Invasive oncologic procedures require thorough preoperative
      planning and staging to accomplish the goal of tumor-free margins. Patient
      factors, specifically tumor type, grade, anatomic location, and extent of local
      invasion, will subsequently dictate the appropriate resection and reconstructive
      options available. Resection of the tumor with a wide margin of normal tissue is
      the surgeon's primary objective. The reconstructive phase of the surgery
      endeavors to restore functional and cosmetic integrity to the regional anatomy.
      Each resection and reconstruction procedure must be customized for the patient's
      disease. Thoughtful preoperative planning, timing, and intraoperative flexibility
      to unforeseen circumstances will minimize complications. Armed with a number of
      reconstructive options for each case, the surgeon develops intraoperative
      flexibility and latitude to be more aggressive during the primary resection. If
      the surgeon self-imposes limitations on the aggressive removal of the primary
      tumor by virtue of tissue closure concerns, the completeness of resection and
      patient survival may well be jeopardized. As familiarity and experience with
      different reconstructive options increases, the surgeon will have greater
      confidence in removing large volumes of diseased tissue.

PMID- 9634353
TI  - Airway Inflammation and Remodelling in Asthma: Implications for Asthma Therapy.
      Proceedings of a workshop. Quebec City, Canada, March 29-30, 1996.

PMID- 9634354
TI  - Veterinary education enters the university.

PMID- 9634355
TI  - Researchers discover likely link between human, canine gene and blindness.

PMID- 9634356
TI  - Characteristics of the febrile response in Pekin ducks.
AB  - We measured body temperature in Pekin ducks for 22 h after intravenous injection
      of the lipopolysaccharide (LPS) of gram negative bacteria at doses of 0, 1, 10,
      and 100 micrograms.kg body mass (-1). The ducks developed monophasic fevers
      showing increases in peak temperature reached and duration of fever with
      increases in dose of LPS. Body temperatures of unrestrained telemetered ducks
      without access to food and water were similar to those of saline-injected
      controls in the fever experiments, but were lower in the morning than when the
      same birds had access to food and water. This nocturnal hypothermia may have
      resulted from energy restriction imposed by lack of food and water. The dose of
      LPS required to elicit a fever of over 18 h duration (100 micrograms.kg-1) will
      elicit a biphasic fever of 5 h duration in rats. Pekin ducks did not exhibit
      biphasic fever even at the highest LPS dose administered, indicating that while
      fever is superficially similar in the two homeothermic classes, there may be
      differences in details of the mechanism. The similarities of the dose/response
      characteristics to that of mammals lends support to the theory that fever in
      vertebrates has a common phyletic origin.

PMID- 9634357
TI  - 4th Conference of the Federation of Infection Societies. Manchester, United
      Kingdom, November 26-28, 1997. Abstracts.

PMID- 9634358
TI  - Retraction: A rabbit model for human cytomeglovirus--induced chorioretinal
      disease (J Infect Dis 1993;168:336-44).

PMID- 9634359
TI  - Retraction.

PMID- 9634360
TI  - [Clinical study on azithromycin in 10% fine granules and 100mg capsules in the
      field of pediatrics].
AB  - Azithromycin (AZM), a new oral macrolide antibiotic, in 10% fine granules or 100
      mg capsules was given to pediatric patients to treat various infections. The
      following results were obtained in our studies of AZM for its antibacterial
      activities against clinical isolates, its pharmacokinetics, its efficacy, and its
      safety. 1. MICs of AZM, erythromycin (EM) and clarithromycin (CAM) were
      determined against a total of 57 strains all at 10(6) cfu/ml. Among Gram-positive
      cocci, MICs of AZM ranged from 0.78 to > 100 micrograms/ml against Staphylococcus
      aureus (20 strains), from 0.05 to 0.1 microgram/ml against Streptococcus pyogenes
      (11 strains), and from 0.0125 to 3.13 micrograms/ml against Streptococcus
      pneumoniae (10 strains). These MICs were similar to those of the other
      macrolides. Among Gram-negative bacilli, MICs of AZM were 0.05 micrograms/ml
      against Moraxella subgenus Branhamella catarrhalis (1 strain), from 0.78 to 3.13
      micrograms/ml against Haemophilus influenzae (9 strains), 0.78 micrograms/ml
      against Haemophilus parainfluenzae (1 strain) and 6.25 micrograms/ml against
      salmonella sp. (1 strain). These values were similar to or lower than those of
      the other macrolides. Against Mycoplasma pneumoniae, MICs of AZM were < or =
      0.0008 micrograms/ml in three strains. One strain of M. pneumoniae showed
      tolerance to AZM at MIC 25 micrograms/ml. The other agents exhibited higher MIC
      than AZM against this organism. 2. Plasma samples were collected from five
      patients receiving fine granules and four patients receiving capsules for drug
      level determination. The patients received AZM at 10.0 approximately 16.3 mg/kg
      body weight once daily for 3 days. Drug concentrations in plasma at two hours
      after Day 3 dosing were in a range between 0.02 and 0.19 micrograms/ml for fine
      granules and were in a range between 0.11 and 0.42 micrograms/ml for capsules. 3.
      Urine samples were collected from four patients receiving fine granules and four
      patients receiving capsules. Drug levels were determined to be 3 micrograms/ml at
      post-treatment 48 hours for fine granules and post-treatment 72 hours for
      capsules. Urinary excretion rates of AZM in three patients on capsules lied in a
      range between 4.69 and 10.17%. 4. Effectiveness of AZM in fine granules was
      evaluated in 128 patients having a total of 19 different infections. AZM was
      rated "excellent" in 51 patients, "good" in 63, "fair" in 8, "poor" in 6,
      resulting in an efficacy rate of 89.1%. Effectiveness of AZM in capsular form was
      evaluated in 23 patients with five different infections. AZM was found
      "excellent" in 13 patients and "good" in 10, resulting in an efficacy rate of
      100%. 5. AZM in fine granules eradicated 45 strains of 54 in 8 different
      bacteria. AZM in capsules eradicated 9 strains of 10 strains in 6 different
      bacteria. 6. As for adverse reactions, one patient complained of eruption, one
      vomiting, one loose stool, five diarrhea, when administered with fine granular
      form of AZM. One patient on AZM capsules experienced urticaria and vomiting. 7.
      As for abnormal laboratory changes, three patients were found with decreased WBC,
      seven with increased eosinophil, two with increased GOT and GPT, one with
      increased GPT. They were all on fine granular form of AZM. As far as
      abnormalities found in patients administered with AZM in capsular form, two
      showed decreased WBC, one decreased WBC along with increased eosinophil, and
      three increased eosinophil.

PMID- 9634361
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 19-1998. A 70-year-old man with diarrhea, polyarthritis, and a
      history of Reiter's syndrome.

PMID- 9634362
TI  - Computed tomography of the appendix.

PMID- 9634363
TI  - Computed tomography of the appendix.

PMID- 9634364
TI  - Computed tomography of the appendix.

PMID- 9634365
TI  - Estimates of the probability of death from burn injuries.

PMID- 9634366
TI  - Estimates of the probability of death from burn injuries.

PMID- 9634367
TI  - X-linked Wiskott-Aldrich syndrome in a girl.

PMID- 9634368
TI  - X-linked Wiskott-Aldrich syndrome in a girl.

PMID- 9634369
TI  - Suicides after natural disasters.

PMID- 9634370
TI  - Dyslexia.

PMID- 9634371
TI  - Dyslexia.

PMID- 9634372
TI  - Dyslexia.

PMID- 9634373
TI  - Dyslexia.

PMID- 9634374
TI  - Acute hepatic porphyrias and primary liver cancer.

PMID- 9634375
TI  - 7th Annual Summer Neuropeptide Conference. Key West, Florida, USA. June 22-26,
      1997. Abstracts.

PMID- 9634376
TI  - Proceedings of the Terry Cutress Symposium. Dunedin, 28 August 1997. Part I.

PMID- 9634377
TI  - Malignant neoplasms metastatic to gingivae.
AB  - Malignant neoplasms metastatic to the gingivae are rare. Our review of the
      literature revealed only eight acceptable examples. We are reporting two
      additional cases. One patient was a 58-year-old man with an adenocarcinoma of the
      lung which metastasized bilaterally to the maxillary gingiva. The second patient
      was a 27-year-old man with a synovial sarcoma which metastasized to multiple
      sites in the maxillary and mandibular gingiva. Clinically, gingival metastatic
      lesions are most often confused with hemangioma, pyogenic granuloma, giant-cell
      granuloma, and pepripheral fibroma. They usually occur late in the course of the
      disease and are associated with metastatic deposits in many other organs and
      tissues. Death usually occurs in a few weeks or months after discovery of the
      gingival metastasis.

PMID- 9634378
TI  - [Remembering Professor Kamillo Vidakovits, M.D., first director of the Surgical
      Clinic of the Szeged Medical University].

PMID- 9634380
TI  - [Bone metastases I].

PMID- 9634379
TI  - [In memory of Dezso Hosz].

PMID- 9634381
TI  - Proceedings of the 14th Pfefferkorn Conference. Belleville, Illinois, USA. August
      6-11, 1995.

PMID- 9634382
TI  - ["Our problem will no doubt be to face the demand". Interview by Roger D. Weill].

PMID- 9634383
TI  - [Gene technology and dentistry].

PMID- 9634384
TI  - [The modern practice team. The prophylaxis assistant, dental hygienist and the
      dentist--organizational recommendations for practice].

PMID- 9634385
TI  - [SwiDent--to whom is this insurance of use? The thoughts of a woman dental
      practitioner after the risk assessment seminar of 13 March 1998].

PMID- 9634386
TI  - [SwiDent does not work out for the patient].

PMID- 9634387
TI  - [Involvement in the interests of youth. The dental health study of the Solothurn
      Dentists Society].

PMID- 9634388
TI  - [Esthetics in implantology. "Esthetic Perfection in Oral Implantology"--the
      course of 17 to 18 October 1997 in Zurich].

PMID- 9634389
TI  - Radiocarbon dates of Kennewick Man.

PMID- 9634390
TI  - Research on auditory cortex plasticity.

PMID- 9634391
TI  - One infant's memory of Oedipus.

PMID- 9634392
TI  - One infant's memory of Oedipus.

PMID- 9634393
TI  - AIDS office head picked.

PMID- 9634394
TI  - Funders reassure genome sequencers.

PMID- 9634395
TI  - Groups vie for space chimp colony.

PMID- 9634396
TI  - WHO's slow road to funding reform.

PMID- 9634397
TI  - EU ends 10-year battle over biopatents.

PMID- 9634398
TI  - Taiwan trolls for U.S. firms to help it create an industry.

PMID- 9634399
TI  - Building a better aspirin.

PMID- 9634400
TI  - Antibodies stage a comeback in cancer treatment.

PMID- 9634401
TI  - The salt of Europa.

PMID- 9634402
TI  - Kinases and phosphatases--a marriage is consummated.

PMID- 9634403
TI  - Challenges for European biology.

PMID- 9634404
TI  - The ethics of AIDS vaccine trials.

PMID- 9634405
TI  - The ethics of AIDS vaccine trials.

PMID- 9634406
TI  - The ethics of AIDS vaccine trials.

PMID- 9634407
TI  - Astrobiology institute picks partners.

PMID- 9634408
TI  - Panel issues plea to boost FDA research.

PMID- 9634409
TI  - Solving the brain's energy crisis.

PMID- 9634410
TI  - New clues to alcoholism risk.

PMID- 9634411
TI  - Growing joints use their noggins.

PMID- 9634412
TI  - New method churns out TB mutants.

PMID- 9634413
TI  - Obesity: how big a problem?

PMID- 9634414
TI  - As obesity rates rise, experts struggle to explain why.

PMID- 9634415
TI  - Uncoupling proteins provide new clue to obesity's causes.

PMID- 9634416
TI  - Cloning for profit.

PMID- 9634417
TI  - What's the best sound?

PMID- 9634418
TI  - More deafness genes.

PMID- 9634419
TI  - 6th International Limb Development and Regeneration Conference. Sun Valley,
      Idaho, USA. 1998. Abstracts.

PMID- 9634420
TI  - Radiotherapy at the End of the 20th Century: Current Role and Future Perspectives
      in Clinical Oncology. Milano, Italy, 31 March-2 April 1998.

PMID- 9634421
TI  - On the 60th anniversary of the dismissal of Jewish Faculty members from the
      Vienna Medical School. Conferences held in Austria in 1998.

PMID- 9634422
TI  - Histologic processing of thick tissue specimens from cytology slides.

PMID- 9634423
TI  - Guidelines for Clinical Evaluation, Development, and Regulation of Lipid-Acting
      Anti-Atherosclerosis Agents.

PMID- 9634424
TI  - Images in neuroscience. Brain development, III. Cerebral cortex.

PMID- 9634425
TI  - Predictors of systemic embolism in patients with mitral stenosis. A prospective
      study.
AB  - BACKGROUND: Most studies of the predictors of systemic embolism in patients with
      mitral stenosis have been retrospective. OBJECTIVE: To prospectively study
      factors associated with systemic embolism in mitral stenosis. DESIGN: Prospective
      cohort study. SETTING: University-affiliated medical institution with 3000 beds.
      PATIENTS: 534 consecutive patients with a mitral valve area of 2.0 cm2 or less;
      132 patients were in sinus rhythm, and 402 were in atrial fibrillation.
      MEASUREMENTS: Nine clinical and 10 echocardiographic variables were assessed for
      prediction of systemic embolism over a mean (+/- SD) follow-up of 36.9 +/- 22.5
      months. Diagnosis of systemic embolism was based on symptoms and signs (sudden
      onset of peripheral arterial ischemic or neurologic manifestations without
      prodromes) and on findings on computed tomography, angiography, and surgery.
      RESULTS: For patients in sinus rhythm, age (relative risk [RR], 1.12 [95% CI,
      1.04 to 1.21]), the presence of a left atrial thrombus (RR, 37.1 [CI, 2.82 to
      487.8]), mitral valve area (RR, 16.9 [CI, 1.53 to 187.0]), and the presence of
      significant aortic regurgitation (RR, 22.4 [CI, 2.72 to 184.8]) were positively
      associated with embolism. For patients in atrial fibrillation, previous embolism
      (RR, 3.11 [CI, 1.66 to 5.85]) was positively associated with embolism;
      percutaneous balloon mitral commissurotomy (RR, 0.37 [CI, 0.18 to 0.79]) was a
      negative predictor. CONCLUSIONS: It may be prudent to give anticoagulants not
      only to patients in atrial fibrillation and patients with previous systemic
      embolism but also to those showing a left atrial thrombus or significant aortic
      regurgitation on echocardiography. Early percutaneous balloon mitral
      commissurotomy may also help prevent systemic embolism in patients with mitral
      stenosis.

PMID- 9634426
TI  - Diagnostic yield and optimal duration of continuous-loop event monitoring for the
      diagnosis of palpitations. A cost-effectiveness analysis.
AB  - BACKGROUND: Continuous-loop event recorders are widely used for the evaluation of
      palpitations, but the optimal duration of monitoring is unknown. OBJECTIVE: To
      determine the yield, timing, and incremental cost-effectiveness of each week of
      event monitoring for palpitations. DESIGN: Prospective cohort study. PATIENTS:
      105 consecutive outpatients referred for the placement of a continuous-loop event
      recorder for the evaluation of palpitations. MEASUREMENTS: Diagnostic yield,
      incremental cost, and cost-effectiveness for each week of monitoring. RESULTS:
      The diagnostic yield of continuous-loop event recorders was 1.04 diagnoses per
      patient in week 1, 0.15 diagnoses per patient in week 2, and 0.01 diagnoses per
      patient in week 3 and beyond. Over time, the cost-effectiveness ratio increased
      from $98 per new diagnosis in week 1 to $576 per new diagnosis in week 2 and
      $5832 per new diagnosis in week 3. CONCLUSIONS: In patients referred for
      evaluation of palpitations, the diagnostic yield of continuous-loop event
      recording decreases rapidly after 2 weeks of monitoring. A 2-week monitoring
      period is reasonably cost-effective for most patients and should be the standard
      period for continuous-loop event recording for the evaluation of palpitations.

PMID- 9634427
TI  - Increased risk for cancer in patients with the Peutz-Jeghers syndrome.
AB  - BACKGROUND: Some reports describe an increased risk for cancer in patients with
      the Peutz-Jeghers syndrome. OBJECTIVE: To characterize occurrences of cancer in a
      large cohort of patients with the Peutz-Jeghers syndrome. DESIGN: Retrospective
      cohort study. SETTING: Tertiary care center. PATIENTS: 34 patients with the Peutz
      Jeghers syndrome identified from Mayo Clinic records from 1945 to 1996.
      MEASUREMENTS: Cases of cancer documented by chart review and telephone follow-up.
      RESULTS: 26 cases of noncutaneous cancer developed in 18 of the 34 patients: 10
      cases of gastrointestinal cancer and 16 cases of extraintestinal cancer. With the
      use of SEER (Surveillance, Epidemiology, and End Results) data for comparison,
      the relative risk for cancer was 18.5 (95% CI, 8.5 to 35.2) in women with the
      Peutz-Jeghers syndrome and 6.2 (CI, 2.5 to 12.8) in men with the syndrome (P =
      0.001). In women, the relative risk for breast and gynecologic cancer was 20.3
      (CI, 7.4 to 44.2). CONCLUSIONS: The Peutz-Jeghers syndrome is associated with an
      increased risk for cancer. The relative risk for breast and gynecologic cancers
      is particularly high.

PMID- 9634428
TI  - Family history of colorectal adenomatous polyps and increased risk for colorectal
      cancer.
AB  - BACKGROUND: The risk for colorectal cancer among family members of patients with
      colorectal cancer is well established, but the risk among family members of
      patients with colorectal adenomas is less well established. OBJECTIVE: To examine
      the risk for colorectal cancer among first-degree relatives of patients with
      adenoma compared with that among first-degree relatives of controls without
      adenoma. DESIGN: Reconstructed cohort study. SETTING: Three university-based
      colonoscopy practices in New York City. PATIENTS: 1554 first-degree relatives of
      244 patients with newly diagnosed adenomas and 2173 first-degree relatives of 362
      endoscopically normal controls. MEASUREMENTS: Structured interviews were used to
      obtain family history. Adjusted relative risks (RR) were estimated from Cox
      proportional hazards regression models. RESULTS: The risk for colorectal cancer
      was elevated (RR, 1.74 [95% CI, 1.24 to 2.45]) among first-degree relatives of
      patients with newly diagnosed adenomas compared with the risk among first-degree
      relatives of controls. This increased risk was the same for parents (RR, 1.58
      [CI, 1.07 to 2.34]) and siblings (RR, 1.58 [CI, 0.81 to 3.08]). First-degree
      relatives of patients with adenomas did not have elevated risk for other cancers.
      The risk for colorectal cancer among family members increased with decreasing age
      at diagnosis of adenoma in probands. Among first-degree relatives of patients who
      were 50 years of age or younger when the adenoma was diagnosed, the risk was more
      than four times greater (RR, 4.36 [CI, 2.24 to 8.51]) than that among first
      degree relatives of patients who were older than 60 years of age when the adenoma
      was diagnosed. CONCLUSIONS: First-degree relatives of patients with newly
      diagnosed adenomas, particularly of patients who are 50 years of age or younger
      at diagnosis, are at increased risk for colorectal cancer and should undergo
      screening similar to that recommended for relatives of patients with colorectal
      cancer.

PMID- 9634429
TI  - Multiple concurrent reverse transcriptase and protease mutations and multidrug
      resistance of HIV-1 isolates from heavily treated patients.
AB  - BACKGROUND: Drug resistance of HIV-1 is an obstacle to the long-term efficacy of
      antiretroviral therapy. OBJECTIVE: To characterize reverse transcriptase and
      protease genes of multidrug-resistant HIV-1 isolates. DESIGN: Descriptive case
      series. SETTING: Academic medical center. PATIENTS: Four consecutive patients
      with HIV-1 infection were selected because they had previously received many
      antiretroviral drugs and had not achieved plasma HIV-1 RNA suppression despite
      treatment with several three-drug combinations. MEASUREMENTS: Reverse
      transcriptase sequencing, protease sequencing, and drug susceptibility testing of
      HIV-1. RESULTS: Isolates of HIV-1 from the four patients shared seven protease
      mutations and eight reverse transcriptase mutations. These mutations were present
      in biological clones and at three time points in three of the patients.
      Susceptibility testing showed high-level resistance (30-fold to >100-fold) to
      zidovudine, lamivudine, saquinavir, indinavir, and nelfinavir and lower-level
      resistance (3-fold to 5-fold) to didanosine, zalcitabine, and stavudine.
      CONCLUSIONS: Simultaneous resistance to almost all available antiretroviral drugs
      may occur in HIV-1. The concordance and persistence of mutations in drug
      resistant HIV-1 isolates suggest that some combinations of reverse transcriptase
      and protease mutations give the virus a selective advantage in the presence of
      various drug combinations.

PMID- 9634431
TI  - Market influences on internal medicine residents' decisions to subspecialize.
AB  - BACKGROUND: Managed care reduces the demand for internal medicine subspecialists,
      but little empirical information is available on how increasing managed care may
      be affecting residents' training choices. OBJECTIVE: To determine whether
      increased managed care penetration into an area where residents train was
      associated with a decreased likelihood that residents who completed general
      internal medicine training pursued subspecialty training. DESIGN: Secondary
      logistic regression analysis of data from the 1993 cohort of general internal
      medicine residents. SETTING: U.S. residency training sites. PARTICIPANTS: 2263
      U.S. medical school graduates who completed general internal medicine residency
      training in 1993. MEASUREMENTS: The outcome variable (enrollment in subspecialty
      training) was derived from the Graduate Medical Education Tracking Census of the
      Association of American Medical Colleges (AAMC). Health maintenance organization
      (HMO) penetration (possible range, 0.0 to 1.0; higher values indicate greater
      penetration) was taken from the Interstudy Competitive Edge Database. Individual
      and medical school covariates were taken from the AAMC's Student and Applicant
      Information Management System database and the National Institutes of Health
      Information for Management Planning, Analysis, and Coordination system. The U.S.
      Census division was included as a control covariate. RESULTS: 980 participants
      (43%) enrolled in subspecialty training. Logistic regression analyses indicated a
      nonlinear association between managed care penetration into a training area and
      the odds of subspecialization. Increasing managed care penetration was associated
      with decreasing odds of subspecialization when penetration exceeded 0.15. The
      choice of subspecialty training increased as HMO penetration increased from 0 to
      0.15. CONCLUSIONS: Local market forces locally influenced the career decisions of
      internal medicine residents, but the influence was small compared with the
      effects of age and sex. These results suggest that market forces help to achieve
      more desirable generalist-to-specialist physician ratios in internal medicine.

PMID- 9634430
TI  - Nodular cutaneous microsporidiosis in a patient with AIDS and successful
      treatment with long-term oral clindamycin therapy.
AB  - BACKGROUND: In AIDS, nodular skin disease can result from various causes.
      OBJECTIVE: To report a new manifestation of microsporidial infection presenting
      as nodular skin disease with underlying osteomyelitis. DESIGN: Case report.
      SETTING: Tertiary-care military medical center in Washington, D.C. PATIENT: A 36
      year-old woman with late-stage AIDS who presented with disseminated, nodular
      cutaneous lesions and underlying osteomyelitis. MEASUREMENTS: Disseminated
      microsporidial infection with an Encephalitozoon-like species was diagnosed by
      electron microscopic examination of material obtained from the skin lesions.
      INTERVENTION: The patient received long-term oral clindamycin therapy, which
      cured her disseminated infection. CONCLUSIONS: Microsporidia can cause
      disseminated cutaneous infections in AIDS patients. The response of this patient
      to long-term clindamycin therapy merits further evaluation.

PMID- 9634432
TI  - Epidemiology of human rabies in the United States, 1980 to 1996.
AB  - PURPOSE: To summarize the epidemiologic, diagnostic, and clinical features of the
      32 laboratory-confirmed cases of human rabies diagnosed in the United States from
      1980 to 1996. DATA SOURCES: Data were obtained from case reports of human rabies
      submitted to the Centers for Disease Control and Prevention by state or local
      health authorities. STUDY SELECTION: All cases of human rabies reported in the
      United States from 1980 to 1996 in which infection with rabies virus was
      confirmed by laboratory studies. DATA EXTRACTION: Patients were reviewed for
      demographic characteristics, exposure history, rabies prophylaxis, clinical
      presentation, treatment, clinical course, diagnostic laboratory tests,
      identification of rabies virus variants, and the number of medical personnel or
      family members who required postexposure prophylaxis after coming in contact with
      an exposed person. DATA SYNTHESIS: 32 cases of human rabies were reported from 20
      states. Patients ranged in age from 4 to 82 years and were predominantly male
      (63%). Most patients (25 of 32) had no definite history of an animal bite or
      other event associated with rabies virus transmission. Of the 32 cases, 17 (53%)
      were associated with rabies virus variants found in insectivorous bats, 12 (38%)
      with variants found in domestic dogs outside the United States, 2 (6%) with
      variants found in indigenous domestic dogs, and 1 (3%) with a variant found in
      indigenous skunks. Among the 7 patients with a definite exposure history, 6 cases
      were attributable to dog bites received in foreign countries and 1 was
      attributable to a bat bite received in the United States. In 12 of the 32
      patients (38%), rabies was not clinically suspected and was diagnosed after
      death. In the remaining 20 cases (63%), the diagnosis of rabies was considered
      before death and samples were obtained specifically for laboratory confirmation a
      median of 7 days (range, 3 to 17 days) after the onset of clinical signs. Of the
      clinical differences between patients in whom rabies was diagnosed before death
      and those in whom it was diagnosed after death, the presence of hydrophobia or
      aerophobia was significantly associated with antemortem diagnosis (odds ratio,
      11.0 [95% CI, 1.05 to 273.34]). The median number of medical personnel or
      familial contacts of the patients who received postexposure prophylaxis was 54
      per patient (range, 4 to 179). None of the 32 patients with rabies received
      postexposure prophylaxis before the onset of clinical disease. CONCLUSIONS: In
      the United States, human rabies is rare but probably underdiagnosed. Rabies
      should be included in the differential diagnosis of any case of acute, rapidly
      progressing encephalitis, even if the patient does not recall being bitten by an
      animal. In addition to situations involving an animal bite, a scratch from an
      animal, or contact of mucous membranes with infectious saliva, postexposure
      prophylaxis should be considered if the history indicates that a bat was
      physically present, even if the person is unable to reliably report contact that
      could have resulted in a bite. Such a situation may arise when a bat bite causes
      an insignificant wound or the circumstances do not allow recognition of contact,
      such as when a bat is found in the room of a sleeping person or near a previously
      unattended child.

PMID- 9634433
TI  - Mosquitoes and mosquito repellents: a clinician's guide.
AB  - This paper is intended to provide the clinician with the detailed and scientific
      information needed to advise patients who seek safe and effective ways of
      preventing mosquito bites. For this review, clinical and analytical data were
      selected from peer-reviewed research studies and review articles, case reports,
      entomology texts and journals, and government and industry publications. Relevant
      information was identified through a search of the MEDLINE database, the World
      Wide Web, the Mosquito-L electronic mailing list, and the Extension Toxicology
      Network database; selected U.S. Army, U.S. Environmental Protection Agency, and
      U.S. Department of Agriculture publications were also reviewed. N,N-diethyl-3
      methylbenzamide (DEET) is the most effective, and best studied, insect repellent
      currently on the market. This substance has a remarkable safety profile after 40
      years of worldwide use, but toxic reactions can occur (usually when the product
      is misused). When DEET-based repellents are applied in combination with
      permethrin-treated clothing, protection against bites of nearly 100% can be
      achieved. Plant-based repellents are generally less effective than DEET-based
      products. Ultrasonic devices, outdoor bug "zappers," and bat houses are not
      effective against mosquitoes. Highly sensitive persons may want to take oral
      antihistamines to minimize cutaneous reactions to mosquito bites.

PMID- 9634434
TI  - Letter from Reykjavik.
AB  - Medical care in Iceland can be viewed as an experiment of nature. This small
      island society has combined the Nordic social and welfare structures with
      advanced international medicine. The Vikings settled Iceland in the ninth
      century, and the population has remained biologically homogeneous because of its
      remote isolation. This homogeneity may provide a unique opportunity to contribute
      to the understanding of the genetics of common disorders. Iceland's isolation has
      also limited the resources that are available for clinical training. Therefore,
      it has been necessary for most physicians who graduate from the medical school at
      the University of Iceland to obtain postgraduate training abroad. This has been
      of enormous benefit to Icelandic medicine. Fewer opportunities for foreign
      medical graduates to train in the United States would have a substantial effect
      on the future practice of Icelandic medicine. The Icelandic health care system
      faces many challenges. Because health care spending has been reined in,
      priorities must be set more clearly than in the past, and heated discussions have
      erupted about gatekeeping and merging of hospitals. These have been "interesting
      times" for Icelandic medicine. Other countries may learn lessons from our medical
      situation: a microcosm, to be sure, but no longer an isolated one.

PMID- 9634435
TI  - What's new in transplant immunology: problems and prospects.
AB  - In the past 40 years, transplantation has moved from an experimental form of
      therapy used almost exclusively for renal failure to an accepted treatment for
      end-stage kidney disease, heart disease, liver disease, lung disease, and
      diabetes mellitus. Tissue transplantation for conditions from thermal injury to
      Parkinson disease is being investigated. The primary barrier in transplantation
      medicine is the immunologic reaction of the recipient to donor organs and
      tissues. Currently available drugs permit excellent short-term graft survival but
      have not led to reliable long-term survival. Recent advances in the understanding
      of this immune response have suggested new approaches to induction of immunologic
      tolerance and reduction of late graft losses. Because of the excellent short-term
      success of current agents, integration of these new approaches into clinical
      trials is challenging and raises important questions about the design of such
      trials.

PMID- 9634436
TI  - On the death of house officers.

PMID- 9634437
TI  - Resisting resistance: maximizing the durability of antiretroviral therapy.

PMID- 9634438
TI  - Death in springtime.

PMID- 9634439
TI  - Interferon-alpha in chronic hepatitis C.

PMID- 9634440
TI  - Successful treatment of hyperammonemia after lung transplantation.

PMID- 9634441
TI  - Adult (not internal) medicine.

PMID- 9634442
TI  - Adult (not internal) medicine.

PMID- 9634443
TI  - Adult (not internal) medicine.

PMID- 9634444
TI  - Adult (not internal) medicine.

PMID- 9634445
TI  - Adult (not internal) medicine.

PMID- 9634446
TI  - Adult (not internal) medicine.

PMID- 9634447
TI  - Literature and medicine: an on-line guide.

PMID- 9634448
TI  - Immunologic Diseases of the Ear. Conference proceedings. Positano, Italy, October
      24-26, 1996.

PMID- 9634449
TI  - Frontiers of Neurology: A Symposium in Honor of Fred Plum. New York City, New
      York, USA. October 5, 1996.

PMID- 9634450
TI  - Salivary Gland Biogenesis and Function. Proceedings of a conference. Arlie,
      Virginia, USA. November 7-10, 1996.

PMID- 9634451
TI  - Health care report cards.

PMID- 9634452
TI  - Fetal surgery: a brief review.
AB  - Fetal therapy is a logical extension of fetal diagnosis. Fetal surgery has been
      performed in humans for the past 10 years. During this time, technical obstacles
      have been overcome and the natural history of many fetal disorders has been
      defined. A select group of disorders amenable to potential improvement by fetal
      treatment has been identified including fetal urinary tract obstruction, fetal
      diaphragmatic hernia, fetal congenital cystic adenomatoid malformation and fetal
      sacrococcygeal teratoma. The fetal surgical experience with each of these lesions
      is reviewed and the maternal risk of fetal surgery is discussed.

PMID- 9634453
TI  - CT findings in neonatal hypothermia.
AB  - BACKGROUND: Newborn infants are particularly prone to hypothermia, a condition
      with a high mortality. OBJECTIVE: To study the CT brain patterns in infants with
      hypothermia and neurological symptoms. MATERIALS AND METHODS: We reviewed the
      brain CT of nine infants with neonatal hypothermia, multiple organ failure,
      seizures and coma. RESULTS: Two infants had normal CT scans, acutely and at
      follow-up, and were clinically normal at follow-up. In seven infants, CT showed
      diffuse cerebral oedema, with reversal of the normal density relationship between
      grey and white matter and a relative increased density of the thalami, brainstem
      and cerebellum - the 'reversal sign'. In six surviving infants with severe
      developmental delay, follow-up CT revealed cerebral atrophy with multicystic
      encephalomalacia. CONCLUSIONS: The 'reversal sign' has been described in the
      abused child, birth asphyxia and anoxia due to drowning. Neonatal hypothermia is
      offered as a further cause.

PMID- 9634454
TI  - Renal excretion of gadolinium mimicking calculi on non-contrast CT.

PMID- 9634455
TI  - Ultrasonography in the study of salivary gland lesions in children.
AB  - Salivary gland lesions are uncommon in children and may be related to the
      parotid, submandibular or sublingual glands. Inflammatory lesions are the most
      common cause of salivary gland abnormalities in children and can be due to acute
      viral, acute suppurative, or recurrent acute or chronic inflammation.
      Intraparotid lymphadenitis may also occur, as in cat-scratch disease or in other
      causes of cervical lymphadenitis. Salivary gland neoplasms are rare in children,
      and most of them are benign including mainly hemangioma, pleomorphic adenoma, or
      lymphangioma. Other lesions, such as sialolithiasis, mucocele, or ranula, may
      also be seen. Ultrasonography should be the initial imaging study used for the
      examination of salivary gland lesions in children, given the fact that most of
      such lesions are benign and are shown up clearly by sonography. In most cases,
      this technique permits the differentiation of intraglandular and extraglandular
      lesions, and may suggest the correct diagnosis. The entire lesion could not be
      totally depicted by US however, and other imaging techniques such as CT or MRI
      may be necessary. Vascular lesions can be demonstrated more clearly through the
      use of color Doppler imaging. Some of the lesions may appear similar, and
      clinical correlation is important for the differential diagnosis. This article
      discusses the sonographic appearance and clinical manifestations of the spectrum
      of salivary gland abnormalities that may occur in children.

PMID- 9634456
TI  - Preamputation MR imaging in meningococcemia and comparison to conventional
      arteriography.
AB  - Meningococcemia is a life-threatening infection which produces purpura fulminans
      and extremity gangrene in its most severe form. In patients with gangrene,
      amputation is usually necessary. The amputations frequently need revision as
      ischemic changes in the underlying soft tissues and bone are difficult to
      evaluate at the time of surgery. These ischemic changes often have non-vascular
      distributions and progress over time. We present two patients in whom MR imaging
      and MR angiography were performed prior to planned amputation. These cases
      demonstrate the potential utility of MR imaging in this setting, and compare the
      MR angiographic results to conventional arteriography in one of these patients.

PMID- 9634457
TI  - Pyloric muscle in asymptomatic infants: sonographic evaluation and discrimination
      from idiopathic hypertrophic pyloric stenosis.
AB  - OBJECTIVE: To compare the morphological and functional US appearance of the
      pylorus in healthy infants with those suffering from idiopathic hypertrophic
      pyloric stenosis (IHPS) in order to determine the pathological limits and to find
      out the most discriminating morphometric parameter. MATERIALS AND METHODS: The
      pylorus of 84 asymptomatic infants was prospectively evaluated with respect to
      morphology (pyloric length, pyloric diameter, muscle thickness and pyloric
      volume) and function (gastric peristalsis and emptying, pyloric opening and the
      fluid passage). Results were compared with 85 patients with proven IHPS. RESULTS:
      In every normal infant we observed frequent pyloric opening with passage of
      gastric contents and quick gastric emptying. All infants with proven IHPS
      presented with a permanently closed pylorus and exaggerated, retrograde gastric
      peristalsis. For each of the four parameters, highly significant differences (P <
      0.0001) were found between the control and IHPS groups. Pathological limits were
      3 mm for muscle thickness (accuracy 100 %), 15 mm for pyloric length (accuracy 94
      %), 11 mm for pyloric diameter (accuracy 92 %) and 12 ml for pyloric volume
      (accuracy 96 %). CONCLUSIONS: Evaluation of pyloric function plays an important
      role in the diagnosis of IHPS. The morphometric parameters are highly accurate in
      differentiating IHPS from a normal pylorus, muscle thickness being the most
      discriminating parameter.

PMID- 9634458
TI  - US, CT and MR imaging characteristics of nephroblastomatosis.
AB  - OBJECTIVES: To describe the imaging features of nephroblastomatosis with US, CT
      and MR, to point out characteristics of differentiation between nephrogenic rests
      (NR) and Wilms' tumour (WT) and to determine the most appropriate imaging
      modality. MATERIALS AND METHODS: We reviewed the US, CT and MR images of 29 cases
      of histopathologically confirmed nephroblastomatosis sent to our department for
      reference evaluation (German nephroblastoma study). The series included 17
      kidneys with NR, 6 kidneys with WT and 32 kidneys with both NR and WT. RESULTS:
      NR presented as multinodular, peripheral, cortical lesions, the diffuse form of
      distribution being less common. Foci were homogeneous and of low echogenicity,
      density or signal intensity. The lesions were most clearly depicted with contrast
      enhanced CT and T1-weighted (T1-W) MR images. Lesions smaller than 1 cm were
      rarely identified by US. The most reliable criterion to differentiate NR from WT
      was their homogeneity. CONCLUSIONS: Contrast-enhanced CT and T1-W MR images are
      of similar potential and superior to US in the diagnosis of nephroblastomatosis.
      Due to the significant radiation dose of serial CT, MR imaging should be the
      method of choice wherever it is available. The cost-effectiveness and
      availability of US makes it ideal for serial follow-up of known lesions.

PMID- 9634459
TI  - Outcome of residual mediastinal masses of thoracic lymphomas in children: impact
      on management and radiological follow-up strategy.
AB  - BACKGROUND: Following treatment with chemotherapy and radiotherapy, patients with
      thoracic lymphomas may demonstrate benign residual mediastinal masses, composed
      of inflammatory, fibrous or necrotic tissue. Because of the potential risk of
      viable tumour cells within the mass, histological verification of the nature of
      these masses may be requested. OBJECTIVE: To study the outcome of thoracic
      lymphomas in children in order to optimise the radiological follow-up strategy of
      residual mediastinal masses (RMM). MATERIALS AND METHODS: A retrospective study
      of 39 children [24 with Hodgkin's disease (HD), 10 with non-Hodgkin's lymphoma
      (NHL), and 5 with anaplastic lymphoma (AL)]. The results of chest X-rays (CXR)
      and thoracic CT performed at the time of re-assessment were compared with the
      histology of the residual masses (n = 11) or the clinical course (n = 28).
      RESULTS: At the time of re-evaluation, 16/39 patients had residual mediastinal
      enlargement (RME) on CXR, and 18/39 patients had RMM on CT. Good concordance was
      observed between the two imaging modalities (K = 0.69). Two children with a RMM
      died from extra-mediastinal progression. Two children with NHL had active
      residual mediastinal lesions but neither had RMM. Sixteen cases of RMM were
      observed in the remaining 35 children and 9 of these masses were histologically
      verified as benign. A favourable course was observed in these 35 cases.
      CONCLUSIONS: RMM are frequent and generally benign. They are well shown on CXR
      and have a non-specific appearance on CT. Except when required by a treatment
      protocol, they could be submitted to further radiological follow-up before
      contemplating surgical verification.

PMID- 9634460
TI  - Gallbladder contraction in biliary atresia: a pitfall of ultrasound diagnosis.
AB  - In 3 (9 %) of 34 children with biliary atresia, US revealed gallbladder
      contraction following an oral feed, given on admission, but not with subsequent
      feeds. Surgery revealed a Kasai type IIIa biliary atresia with a patent
      communication between the gallbladder and duodenum. We propose that the bile
      ducts may initially have been patent, but then gradually became obliterated
      secondary to inflammation. These cases may explain the development of one type of
      biliary atresia.

PMID- 9634461
TI  - Ossifying renal tumor of infancy presenting as a palpable abdominal mass.
AB  - We report a case of ossifying renal tumor of infancy, which presented as a
      palpable abdominal mass in an otherwise asymptomatic 10-month-old girl. The tumor
      was partially calcified and occupied the renal pelvis, causing severe
      hydronephrosis. The differential diagnosis for a patient this age included Wilms
      tumor, extra-adrenal neuroblastoma, infection, calculus, calcified hematoma and
      ossifying renal tumor of infancy. The child underwent heminephrectomy and is
      currently doing well.

PMID- 9634462
TI  - Ossifying renal cell carcinoma.
AB  - In older children, ossifying renal cell carcinoma is a potential explanation for
      a network of well-organized, curvilinear high-attenuation areas in a renal mass.
      Since ossification of renal cell carcinoma is a favorable tumor marker that
      implies a less extensive resection, it is important to anticipate this tumor
      before surgical resection is undertaken.

PMID- 9634463
TI  - Gastroduodenal intussusception with a gastric antral polyp.

PMID- 9634464
TI  - US demonstration and diagnosis of the midaortic syndrome.
AB  - The midaortic syndrome is a rare entity, typically presenting with hypertension,
      refractory to treatment. The diagnosis is usually made by arteriography. We
      report a child in whom the diagnosis was made by ultrasound, confirmed by
      arteriography and successfully treated by balloon dilatation.

PMID- 9634465
TI  - Head-wag autotomography of the upper cervical spine in infantile torticollis.
AB  - BACKGROUND: Infants with torticollis require evaluation of the entire cervical
      spine for vertebral anomalies as part of the work-up, but open-mouth views to
      assess occiput to C2 are difficult to obtain. OBJECTIVE: To evaluate a "head wag"
      autotomographic technique for the frontal projection of this region. MATERIALS
      AND METHODS: Twenty infants under one year of age were evaluated using this
      technique. RESULTS: Sixteen of 20 could be adequately evaluated using this
      simple, low-radiation-dose procedure. CONCLUSION: For infants with torticollis in
      whom vertebral anomalies need to be excluded, the "head wag" technique is useful.

PMID- 9634466
TI  - Primary ovarian leiomyosarcoma in an adolescent following radiation for
      medulloblastoma.
AB  - Primary ovarian leiomyosarcomas are rare neoplasms of the ovary, particularly in
      the pediatric population. Their occurrence following radiation therapy for
      previous malignancy has important implications. We present a case of primary
      ovarian leiomyosarcoma in an adolescent following therapy for medulloblastoma.

PMID- 9634467
TI  - Cerebral MRI of very low birth weight children at 6 years of age compared with
      the findings at 1 year.
AB  - BACKGROUND: We have previously reported the results of cerebral MRI examinations
      in an unselected year cohort of very low birth weight (VLBW) infants at one year
      of corrected age. Twenty-one (78 %) of 27 infants had abnormal myelination,
      mainly in the central occipital white matter (COWM) and in the centrum semiovale
      (CS), seen on T2-weighted images. Twelve infants had irregular and dilated
      lateral ventricles. We speculated whether these findings indicated perinatal
      periventricular leukomalacia (PVL). Only two infants had completely normal MRI at
      age 1 year. OBJECTIVE: To determine whether the abnormal myelination seen at 1
      year of age, was still present, either as delayed myelination or as gliosis
      caused by perinatal PVL. MATERIALS AND METHODS: In the present study, we report
      the results of follow-up cerebral MRI in 20 of these infants at 6 years of age.
      RESULTS: Most of the children with MRI deviations at 1 year still had
      abnormalities at 6 years. Abnormal myelination in the central occipital white
      matter combined with abnormalities in the CS or with ventricular dilatation at
      age 1 year, presented as gliosis in 12 of 13 children at 6 years of age.
      Abnormalities solely in the COWM at age 1 year had normalised in two of five
      children and persisted as delayed myelination in three at age 6 years. Gliotic
      changes in periventricular white matter were found in 12 of 20 children (60 %).
      Areas most affected were the CS (11 children) and the COWM (9 children). Delayed
      myelination in COWM was found in six children (30 %), combined with gliosis in CS
      in three children. Twelve infants had ventricular dilatation both at 1 and 6
      years of age. CONCLUSIONS: The MRI correlates of PVL, i. e. gliosis and
      ventricular dilatation, are common findings on cerebral MRI at 6 years of age in
      VLBW infants.

PMID- 9634468
TI  - High-resolution US of non-traumatic recurrent dislocation of the peroneal
      tendons: a case report.
AB  - We report the case of a young girl with recurrent sharp pain in the outer aspect
      of the ankle. She had no previous trauma. High-resolution US (HRUS) showed a
      complete intermittent dislocation of the peroneal tendons. Post-traumatic chronic
      peroneal instability is quite common, whereas complete dislocation is rare. HRUS
      is an important adjunct to clinical examination and radiographic evaluation of
      patients with musculoskeletal disorders of the foot and ankle [1]. This paper
      reports its value in non-traumatic recurrent dislocation of the peroneal tendons.

PMID- 9634469
TI  - Ilio-psoas abscess in the paediatric population: treatment by US-guided
      percutaneous drainage.
AB  - BACKGROUND: Image-guided percutaneous drainage has been shown to be a safe and
      effective alternative to surgery in the management of psoas abscess in adults and
      adolescents. There is little information on its use in children. OBJECTIVE: To
      evaluate the safety and efficacy of US-guided percutaneous needle aspiration and
      catheter drainage of ilio-psoas abscesses. MATERIALS AND METHODS: A retrospective
      review of 14 children with 16 ilio-psoas abscesses (10 pyogenic and 4
      tuberculous) who were treated by US-guided percutaneous needle aspiration (n = 5)
      or catheter drainage (n = 9) along with appropriate antimicrobial therapy.
      RESULTS: Percutaneous treatment was successful in 10 of the 14 patients; all
      showed clinical improvement within 24-48 h of drainage and subsequent imaging
      demonstrated resolution of the abscess cavities. Surgery was avoided in all of
      these ten patients except one, who underwent open surgical drainage of
      ipsilateral hip joint pus. Of the other four patients, two had to undergo
      surgical drainage of the ilio-psoas abscesses after failure of percutaneous
      treatment, one improved with antibiotics after needle aspiration failed to yield
      any pus, and one died of continuing staphylococcal septicaemia within 24 h of the
      procedure. There were no procedural complications. CONCLUSIONS: Percutaneous
      drainage represents an effective alternative to surgical drainage as a supplement
      to medical therapy in the management of children with ilio-psoas abscesses.

PMID- 9634470
TI  - Dark spleens and livers on MRI after chemotherapy: is it really iron overload?

PMID- 9634471
TI  - The MIBG super scan.

PMID- 9634472
TI  - Complexity among constituents of the HLA-B*1501 peptide motif.
AB  - Analysis of peptides derived from HLA class I molecules indicates that thousands
      of unique peptides are bound by a single molecular type, and sequence examination
      of the pooled constituents yields a motif which collectively defines the peptides
      bound by a given class I molecule. Motifs resulting from pooled sequencing are
      then used to infer whether particular viral and tumor protein fragments might
      serve as class I-presented peptide therapeutics. Still undetermined from a pooled
      motif is the breadth or range of peptides in the population which are brought
      together to form the pooled motif, and it is therefore not yet known how
      representative of the population a pooled motif is. By employing hollow fiber
      bioreactors for large-scale production of HLA class I molecules, sufficient
      peptides are produced to investigate individual subsets of peptides comprising a
      motif. Edman sequencing and mass spectrometric analysis of peptides eluted from
      HLA-B*1501 reveal that many peptide sequences fail to align with either the N- or
      C-terminal anchors predicted for the B*1501 peptide motif through whole pool
      sequencing. These analyses further reveal auxiliary anchors not previously
      detected and peptides significantly larger and smaller than the predicted
      nonamer, ranging from 6 to 12 amino acids in length. These results demonstrate
      that constituents of the B*1501 peptide pool vary markedly in comparison with one
      another and therefore in comparison with previously established B*1501 motifs,
      and such complexity indicates that many of the peptide ligands presented to CTL
      cannot be predicted using class I consensus motifs as search criteria.

PMID- 9634473
TI  - The influence of exogenous peptide on beta2-microglobulin exchange in the HLA
      complex: analysis in real-time.
AB  - We used an optical biosensor to determine the relative binding affinity of
      peptides to purified HLA class I molecules. In this assay we monitor beta2
      microglobulin (beta2m) exchange within the HLA-A2 molecule, whereby native beta2m
      in the complex is replaced by beta2m immobilized at the surface of the biosensor.
      Quantitative kinetic measurements permit us to obtain association rate (kass),
      dissociation rate (kdiss) and affinity constants (KA) for the beta2m exchange
      reaction, alone, (control) and in the presence of exogenous peptide. We tested a
      panel of six peptides which had been designed and synthesized with an HLA-A2
      binding motif, and had also been tested by the T2-cell binding assay, along with
      control peptides. The biosensor results demonstrate that exogenous peptide
      influences the dynamics of beta2m exchange in a sequence-specific manner. Five of
      six peptides increased the association rate, decreased the dissociation rate, and
      significantly increased the affinity (KA=1. 55-1.88x10(9) M-1) of HLA-A2 for
      immobilized beta2m compared with the control (KA =1.14+/-0.04x10(9)M-1),
      demonstrating stabilization of the complex. One peptide was unable to stabilize
      the complex, as also shown in the T2 binding assay. However, analysis of peptide
      sequences demonstrated that the HLA-A2 secondary motif as well as primary motif
      residues are required for HLA-A2 stabilization. Further experiments demonstrated
      that beta2m exchange alone cannot stabilize the HLA class I complex at the cell
      surface until a peptide of sufficient binding affinity is bound. Hence kinetics
      equal to or below the control values in our biosensor assay probably represent an
      unstable complex in vivo. Unlike other methods described for the analysis of
      peptide stabilization, this approach is significantly faster, provides full
      kinetic analysis, and is simpler, since it requires no labeling of peptides.
      Furthermore, this may have important implications in the assessment of peptide
      vaccines.

PMID- 9634474
TI  - High RAD51 mRNA levels in young rabbit appendix. A role in B-cell gene
      conversion?
AB  - The rabbit has a limited number of VH genes that rearrange. As in the chicken,
      the 3'-most VH1 gene is rearranged in most B lymphocytes. This laboratory
      reported that by 6 weeks after birth, diversification of rearranged VH genes
      occurs, at least in part, by gene conversion-like events in the appendix,
      suggesting that this organ is a homologue of the avian bursa of Fabricius. Rad51
      contributes to the repair of double-strand breaks in DNA during somatic and
      meiotic recombination. The gene was first identified in lower eukaryotes, and
      later in vertebrates including chicken, as encoding an Escherichia coli RecA-like
      protein. We report the cloning and sequencing of RAD51 from the rabbit. Because
      the chicken bursa was shown to express high levels of RAD51 message, we
      investigated the expression of RAD51 in the rabbit appendix and other tissues.
      Using a quantitative polymerase chain reaction mimic assay and conventional
      northern analyses, we found high RAD51 expression in young rabbit appendix
      comparable to levels in testis where there is an abundance of meiotic
      recombination. RAD51 levels were three times higher in appendix B lymphocytes
      compared with T lymphocytes and were lower in adult appendix, as well as in
      spleen and Peyer's patches of young rabbits. We measured the levels of message in
      several appendix cell sub-populations obtained by fluorescence-activated cell
      sorting and found that sub-populations of B lymphocytes corresponding to
      different stages of B-cell development as well as B cells undergoing isotype
      switch did not have significantly different mRNA levels.

PMID- 9634475
TI  - Regulation of expression of the human lymphocyte activation gene-3 (LAG-3)
      molecule, a ligand for MHC class II.
AB  - The lymphocyte activation gene-3 (LAG-3), a major histocompatibility complex
      (MHC) class II ligand evolutionarily related to CD4, is expressed exclusively in
      activated T and NK lymphocytes and seems to play a role in regulating the
      evolving immune response. We first determined that surface LAG-3 expression on
      activated human T cells is upregulated by certain cytokines (IL-2, IL-7, IL-12)
      and not by others (IL-4, IL-6, IL-10, TNF-alpha, TNF-beta, IFN-gamma). Surface
      LAG-3 expression correlated with intracellular IFN-gamma production in both CD4+
      and CD8+ T-cell subsets. We then analyzed the 5' transcription control sequences
      of LAG-3. A DNase I hypersensitive site induced in T cells following cellular
      activation was found in the region including the transcriptional start site,
      showing that DNA accessibility is a mechanism which restricts LAG-3 expression to
      activated T cells. Transcription is initiated at three sites. A GC box, 80 base
      pairs (bp) upstream of the major transcription start site, forms a minimal
      promoter which is regulated by two upstream regions containing positive and
      negative regulatory elements with multiple protein binding sites as shown by
      footprinting analysis. In particular, a GATA/c-Ets motive was identified in a
      short segment homologous to the mouse CD4 distal enhancer, suggesting that LAG-3,
      which is embedded in the CD4 locus, may be controlled by some CD4 regulatory
      elements. Finally, a 100 bp region downstream of the transcription start site was
      shown to be involved in the cell-specific control of LAG-3 expression.
      Understanding this highly regulated expression may help to determine the
      intriguing role of this activation-induced MHC class II ligand.

PMID- 9634476
TI  - Mice carrying a CD20 gene disruption.
AB  - CD20 is a hallmark antigen of B lymphocytes. Its expression is restricted to
      precursor and mature B cells but it is not expressed on plasma cells. The protein
      is a membrane-embedded phosphoprotein that appears likely to transverse the
      membrane four times. Its function is unknown although CD20 has been variously
      proposed to play a role in B-cell activation, proliferation, and calcium
      transport. A unique homologue of human CD20 has been described in mouse, which
      also shows a B-cell-specific pattern of expression. Here we describe the
      generating of mice carrying a CD20 gene disruption. So far, we have failed to
      detect any major effect of the gene disruption on the differentiation and
      function of B lymphocytes as judged by the expression of surface markers, antigen
      receptor signaling, proliferative responses, or calcium uptake. We did note,
      however, that the mice homozygous for the gene disruption [generated by
      intercrossing (129 x C57BL/6)F1 CD20+/- heterozygotes] showed a substantial
      depletion of the sub-population of peritoneal B cells that lack expression of the
      B220 (RA3-6B2) isoform of CD45. The loss of the IgM+ 6B2- peritoneal B cells is
      not, however, attributable to the CD20 gene disruption itself. Rather, it
      segregates with a polymorphic difference between the 129 and C57BL/6 strains that
      is linked to the CD20 locus which, intriguingly, is itself close to the CD5 gene.
      This demonstrates that caution must be exercised when comparing the phenotypes of
      F2 litter-mates generated from crosses between 129 embryonic stem-cell-derived
      chimeras and mice of other strains.

PMID- 9634477
TI  - beta2-Microglobulin in neotropical primates (Platyrrhini).
AB  - Nucleotide sequences for the three exons of the beta2-microglobulin (beta2m) gene
      (B2m) were determined for 135 animals representing 37 species and all 16 genera
      of neotropical primates (Platyrrhini). Twenty-eight different nucleotide
      sequences, encoding for 26 different proteins, were obtained. In comparison with
      those of other primate species, the beta2-microglobulins of the Platyrrhini form
      a distinct clade. Individual genera of neotropical primates have distinctive B2m
      sequences, but within a genera species can have either the same or different B2m
      sequences. B2m polymorphism was found within three of the species sampled:
      Callicebus personatus, Saguinus midas, and Aotus azarae. Of these only the
      polymorphism in A. azarae has an effect upon the mature, functional beta2m
      protein: residue 4 being either alanine or threonine. The A. azarae B2m allele
      encoding alanine at position 4 is shared with another species of Aotus (A.
      infulatus). In pairwise comparison the mature beta2m proteins of neotropical
      primates differ by 1-9 amino acid substitutions which can occur at 18 positions
      within the sequence. The substitutions are distributed throughout the primary
      structure but are more commonly found in loops rather than beta strands of the
      tertiary structure. Of 17 residues of beta2m which hydrogen-bond with the class I
      heavy chain in human MHC class I molecules, 13 are conserved in the neotropical
      primates. The overall pattern of sequence variation in the B2m genes of the
      Platyrrhini is consistent with an evolution by successive selectively neutral
      events.

PMID- 9634478
TI  - Linkage of RXRB-like genes to class I and not to class II Mhc genes in the
      zebrafish.

PMID- 9634479
TI  - Heterogeneity in the genetic basis of human complement C9 deficiency.

PMID- 9634480
TI  - A new HLA-B15 allele (B*1541) found in a Mexican of Nahua (Aztec) descent.

PMID- 9634481
TI  - Characterization of an HLA-A26 serologic variant.

PMID- 9634482
TI  - The HLA-B* 1516 motif demonstrates HLA-B-specific P2 pocket characteristics.

PMID- 9634483
TI  - Eight rat RT1Ba sequences.

PMID- 9634484
TI  - Heterochronic differences of Hoxa-11 expression in Xenopus fore- and hind limb
      development: evidence for lower limb identity of the anuran ankle bones.
AB  - The wrist (carpus) and ankle (tarsus) of most tetrapods, as well as the wrist of
      anurans, contains relatively small nodular skeletal elements. The anuran tarsus,
      however, comprises a pair of long bones, the proximal tarsals tibiale and
      fibulare, which resemble the lower leg bones, tibia and fibula (zeugopodium). In
      this paper we investigate whether the proximal tarsals of Xenopus are of
      zeugopodial character identity, i.e. whether they develop under the influence of
      the same genes that pattern the lower limb. We compare Hoxa-11 expression in the
      forelimb bud with that in the hind limb bud by whole-mount in situ hybridization.
      Hoxa-11 has been implicated in the development of the lower limb. In Xenopus we
      note three differences between Hoxa-11 expression in fore- and hind limb buds:
      (1) Hoxa-11 expression is maintained until the hind limb bud reaches a larger
      size (2 mm) than that of the forelimb bud (1.5 mm); (2) Hoxa-11 expression is
      maintained over larger spatial domains than in the forelimb; and (3) Hoxa-11
      expression has a pronounced posterior polarity in the hind limb, but not in the
      forelimb. Hind limb expression of Hoxa-11 can be understood as a heterochronic
      prolonging of the expression dynamic in the forelimb. Finally we found that the
      proximal tarsals start to develop within the expression domain of Hoxa-11, while
      in the forelimb the lower arm elements reach the distal expression limit of Hoxa
      11. The gene expression data presented here support the notion of a zeugopodial
      identity of the proximal tarsal elements in Xenopus.

PMID- 9634485
TI  - Isolation and characterization of three mRNAs enriched in embryos of the direct
      developing sea urchin Heliocidaris erythrogramma: evolution of larval ectoderm.
AB  - The Australian sea urchin Heliocidaris erythro-gramma utilizes a derived direct
      developmental mode that evolved 8-12 million years ago. From a differential
      screen we have isolated a small set of cDNAs corresponding to genes more greatly
      expressed in embryos of H. erythrogramma than in those of its indirect-developing
      nearest relative, H. tuberculata. The method was biased towards abundant
      transcripts and did not allow detection of modifications of usage of highly
      conserved gene family members. Three differentially expressed abundant
      transcripts were found that potentially encode secreted proteins. Two of these,
      the arylsulfatase HeARS and the putative lectin HeEL-1, were identifiable as
      homologues of known proteins. Another gene, HeET-1, may be exclusively expressed
      in the H. erythrogramma embryo. In situ hybridization experiments demonstrate
      that all three transcripts are localized to the ectoderm. Two of them, HeET-1 and
      HeEL-1, are transcribed in an identical domain comprising the larval ectoderm.
      This region of gene expression has acquired a novel columnar cytology during the
      evolution of the H. erythrogramma embryo. The third sequence, HeARS, encodes an
      arylsulfatase homologue. Its expression is uniform in the gastrula, but as the
      rudiment develops it accumulates to the greatest extent in the invaginating
      vestibular ectoderm. Through comparisons with indirect-developing species, we
      show that this concentration of arylsulfatase mRNA in the rudiment is a novel
      feature of H. erythrogramma development. These data suggest that H. erythrogramma
      has a unique arrangement of ectodermal gene expression territories. We propose
      that these reflect larval adaptations that have occurred in the lineage leading
      to H. erythrogramma, and enabled the evolution of direct development.

PMID- 9634486
TI  - Down-regulation of expression of a pupal cuticle protein gene by transcriptional
      and posttranscriptional control mechanisms during metamorphosis in Galleria.
AB  - Down-regulation of expression of a pupal cuticle protein gene (GmPCP52) was
      investigated during metamorphosis in Galleria during normal development and in
      response to 20-hydroxyecdysone (20 E) and a juvenile hormone analogue
      (epofenonane). The developmental profile of GmPCP52 transcription was traced by
      nuclear run-on transcription assays. Transcription of the GmPCP52 gene is highest
      shortly after pupal ecdysis. There is a rapid decline between a pupal age of 12
      and 18 h. Transcription becomes undetectable at 24 h. 20 E accelerates cessation
      of transcription, but induces a short second period of GmPCP52 transcriptional
      activity. Epofenonane prolongs transcription and induces a second round of
      transcriptional activity in relation to the synthesis of a second pupal cuticle.
      Analysis of changes in poly(A) tail length of GmPCP52 mRNA demonstrated control
      of expression at the level of mRNA translatability and stability. At 6 to 9 h
      poly(A) tails of GmPCP52 mRNA have lengths of 70 to 170 A-residues. From 9 h on
      mRNA with about 50 As accumulates. This material is regarded as translationally
      inactive. From 18 h on, further poly(A) shortening and degradation of the
      transcript occurs. Again, 20 E has an accelerating effect. In accordance with the
      results of the run-on experiments, there is a second increase in GmPCP52 mRNA
      with poly(A) tail lengths greater than 50 A. Epofenonane causes delay but does
      not prevent the changes observed in untreated animals. The results demonstrate,
      that expression of the GmPCP52 gene is regulated at the level of transcription,
      translation, as well as transcript accumulation and degradation. Targets of
      hormonal action are discussed.

PMID- 9634487
TI  - Drosophila OVO zinc-finger protein regulates ovo and ovarian tumor target
      promoters.
AB  - The ovo+ and ovarian tumor+ genes function in the germline sex determination
      pathway in Drosophila, but the hierarchical relationship between them is unknown.
      We found that increased ovo+ copy number resulted in increased ovarian tumor
      expression in the female germline and increased ovo expression in the male
      germline. The ovo locus encodes C2H2 zinc-finger proteins. Bacterially expressed
      OVO zinc-finger domain bound to multiple sites at or near the ovo and ovarian
      tumor promoters strongly suggesting that OVO is directly autoregulatory and that
      ovarian tumor is a direct downstream target of ovo in the germline sex
      determination hierarchy. Both positive and negative regulation by OVO proteins
      appears likely, depending on promoter context and on the sex of the fly. Our
      observation that two strong OVO-binding sites are at the initiator of the TATA
      less ovo-B and ovarian tumor promoters raises the possibility that OVO proteins
      influence the nucleation of transcriptional pre-initiation complexes.

PMID- 9634488
TI  - Otx cognates in a lamprey, Lampetra japonica.
AB  - Gnathostomes have two lineages of Otx genes, Otx1 and Otx2, as cognates of a
      Drosophila head gap gene, orthodenticle. Previous studies with mutant mice have
      demonstrated that they play essential roles in the development of rostral head.
      To shed lights on the evolution of the rostral head in vertebrates we isolated
      their cognates in the Japanese marine lamprey, Lampetra japonica. The lamprey
      genome appeared to have two Otx cognantes, LjOtxA and LjOtxB. Phylogenetic
      analyses suggest that LjOtxA clusters with gnathostome Otx2 genes, but LjOtxB
      does not belong to either the Otx1 or Otx2 lineage. LjOtxA was expressed in the
      forebrain and midbrain with the caudal limit possibly at the midbrain/hindbrain
      junction as gnathostome Otx cognates are, but LjOtxB was not expressed in the
      brain. No Otx1 or Otx2 cognates are known in gnathostomes that are not expressed
      in the brain. Both LjOtxA and LjOtxB were expressed in the olfactory placode,
      epiphysis, optic stalks, and lower and upper lips. LjOtxB was also expressed in
      the eyes, where no LjOtxA transcripts were detected. Thus, Otx1 and Otx2
      functions for the development of forebrain and midbrain in gnathostomes appear to
      be shouldered by LjOtxA alone in the lamprey. LjOtxB may have diverged from the
      stem of the Otx1 and Otx2 lineages and evolved independently.

PMID- 9634490
TI  - Introduction.
AB  - Copyright

PMID- 9634489
TI  - Myosin and actin are necessary for polar lobe formation and resorption in
      Ilyanassa obsoleta embryos.
AB  - During the first mitotic divisions many spiralian embryos form a cytoplasmic
      protrusion at the vegetal pole called the polar lobe. In the gastropod Ilyanassa
      obsoleta the polar lobe is constricted by a contractile ring composed of
      filamentous actin, myosin, and associated proteins, similar to the contractile
      ring of the cleavage furrow. To resolve the role of myosin and actin in polar
      lobe formation and resorption, we have applied 2,3-butanedione monoxime and
      Latrunculin B at different stages of the first cleavage to inhibit myosin and F
      actin, respectively. Our results show that myosin is important for both
      cytokinesis and polar lobe formation. Additionally, we have found that the
      resorption of the polar lobe is a two-step process: the first step is passive,
      driven by the tension of the actin-cortex and the second step is active, in which
      the ATP-hydrolysis of myosin/actin interaction supplies the force to complete the
      resorption of the polar lobe. We have summarized our results in a scheme of the
      first cleavage of Ilyanassa obsoleta.

PMID- 9634491
TI  - Concepts of oxygen transport at the microcirculatory level.
AB  - This article compares and contrasts the classic paradigms underlying the
      development of chronic and acute hypoxia in tumors. The classic theory of
      Thomlinson and Gray suggested that chronic hypoxia is the result of large
      intravascular distances. Newer evidence suggests that a multiplicity of effects
      contribute to this process, including steep longitudinal gradients of partial
      pressure of oxygen (Po2) along the vascular tree before arteriolar entry into
      tumor, rheologic effects on red cell deformability brought on by intravascular
      hypoxia, uneven distribution of red cell fluxes in microvessels leading to plasma
      channels, irregular vascular geometry, and oxygen demand that is out of balance
      with the supply. The most common theories have suggested that vascular stasis is
      the most common source of acute hypoxia. If this were true, the incidence of this
      form of hypoxia would be relatively rare because most studies indicate that total
      stasis probably occurs less than 5% of the time. Studies have suggested, however,
      that spontaneous fluctuation in tumor blood flow, on the microregional level, can
      lead to tissue hypoxia, and total vascular stasis is not required. Spontaneous
      fluctuations in flow and Po2 appear to occur commonly. Thus, the most current
      evidence suggests that tumor oxygenation is in a continuous state of flux.
      Collectively, this new information has important implications for therapy
      resistance and gene expression.

PMID- 9634492
TI  - Modification of tumor blood flow: current status and future directions.
AB  - Suboptimal drug distribution and hypoxia, which can contribute to treatment
      failure, are a direct consequence of the spatial and temporal heterogeneity in
      perfusion that occurs in solid tumors. Therefore, improvements in tumor blood
      flow have wide-ranging therapeutic importance. Paradoxically, controlled
      decreases in tumor blood flow can also be exploited and, if permanent, induce
      extensive tumor cell death on their own. We review the current knowledge of the
      factors controlling tumor blood flow with emphasis on the roles of the
      endogeneous vasodilator nitric oxide and the endogenous vasoconstrictor
      endothelin-1. The potential importance and application of approaches that
      irreversibly damage vascular function, so-called vascular targeting, are also
      discussed. Emphasis is given to the drug-based approaches to vascular targeting
      that are now entering clinical evaluation. There is no doubt that increased
      understanding of the processes that determine blood flow in tumors, coupled with
      the availability of techniques to monitor blood flow noninvasively in the clinic,
      will enable strategies for selectively modifying tumor blood flow to be
      transferred from the laboratory to the clinical setting.

PMID- 9634493
TI  - Transvascular drug delivery in solid tumors.
AB  - The microvessel wall is a barrier for the delivery of various therapeutic agents
      to tumor cells. Tumor microvessels are, in general, more permeable to
      macromolecules than normal vessels. The hyperpermeability is presumably due to
      the existence of large pore structures in the vessel wall, induced by various
      cytokines. The cutoff pore size is tumor dependent, as determined by transport
      studies of nanoparticles. The vascular permeability is heterogeneous in tumors
      and dependent on physicochemical properties of molecules as well as the
      ultrastructure of the vessel wall. The ultrastructure is dynamic and can be
      modulated by the tumor microenvironment. The microenvironment itself can be
      altered by the transvascular transport because the transport may facilitate
      angiogenesis, reduce blood flow, and induce interstitial hypertension in tumors.
      Future studies of transport need to address mechanisms of the barrier formation
      and emphasize development of novel strategies for circumventing or exploiting the
      vascular barrier.

PMID- 9634494
TI  - Tumor pH: implications for treatment and novel drug design.
AB  - Although limited data exist, electrode-measured pH values of human tumors and
      adjacent normal tissues, which are concurrently obtained by the same investigator
      in the same patient, consistently show that the electrode pH (believed to
      represent tissue extracellular pH primarily) is substantially and consistently
      lower in tumor than in normal tissue. In contrast, the 31P-magnetic resonance
      spectroscopy-estimated intracellular pH is essentially identical or slightly more
      basic in tumor compared with normal tissue. As a consequence, the cellular pH
      gradient is substantially reduced or reversed in these tissues. This difference
      provides an exploitable avenue for the treatment of cancer. The extent to which
      drugs exhibiting weakly acid or basic properties are ionized depends on their
      ionization potential (pKa) and the pH of their milieu. Weakly acidic drugs that
      are lipid soluble in their nonionized state diffuse freely across the cell
      membrane and on entering a relatively basic intracellular compartment become
      trapped and accumulate within the cell. This may lead to substantial (10-fold or
      more) differences in the intracellular-to-extracellular drug distribution between
      tumor and normal tissue for cytotoxics, hypoxic cell sensitizers, or other drugs
      exhibiting appropriate pKa. Experimental in vitro evaluation of these predictions
      confirms both the predicted pH gradient-dependent changes in cellular drug
      accumulation and toxicity.

PMID- 9634495
TI  - Evaluating tumor biology and oncological disease with positron-emission
      tomography.
AB  - The usefulness of positron-emission tomography (PET) for noninvasive assessment
      of several biological parameters of neoplastic tissue has been reviewed. Numerous
      radiotracers have been developed, whose particular distribution in the presence
      of cancer in vivo serves to distinguish medically relevant properties of the
      tumor cells with which they associate. That distribution is most accurately
      determined through use of a PET scanner, to localize and quantify the tracer
      molecules, in which have been incorporated positron-emitting isotopes. These
      tracers include hypoxia markers, receptor ligands, substrates for enzymatic
      modification by the products of expression of specific genes, and precursors of
      protein anabolism and carbohydrate catabolism. In addition, application of PET to
      evaluation of patients with some particular cancers has been examined, while
      placing special emphasis on the level of scientific rigor of the evidence
      underlying conclusions about appropriate use of PET in oncology.

PMID- 9634496
TI  - Magnetic resonance imaging techniques for monitoring changes in tumor oxygenation
      and blood flow.
AB  - The application of functional magnetic resonance (MR) imaging techniques to the
      measurement of oxygenation and blood flow in tumors is described. Gradient
      recalled echo MR imaging (GRE-MRI) offers a real-time noninvasive method for
      monitoring tumor response to vasomodulators such as carbogen (95% O2/5% CO2)
      breathing in attempts to overcome tumor hypoxia and improve treatment efficacy.
      Although the response is tumor-type dependent, increases in signal intensity of
      up to 100% have been observed in several animal tumor types. Responses are also
      seen in human tumors. The observed increases in GRE-MRI signal intensity are due
      to a combination of a reduction of deoxyhemoglobin in the blood causing changes
      in the MR imaging relaxation time T2* and changes in blood flow and may also
      reflect the capillary density. Thus, the magnitude of the GRE image intensity
      change gives an indication of the potential response of an individual tumor to
      treatments that aim to improve tissue oxygenation and therefore how the tumor may
      respond to therapy. In addition, carbogen breathing by the host has been shown to
      increase the uptake and efficacy of chemotherapeutic agents in animal tumors.

PMID- 9634497
TI  - Microenvironmental control of gene expression: implications for tumor
      angiogenesis, progression, and metastasis.
AB  - Low oxygen tension (hypoxia) is an important prognostic factor in cancer
      treatment because it affects tumor formation and malignant progression. Many
      genes governing these complex processes have been found to be oxygen regulated.
      This article reviews the present knowledge of hypoxia-inducible gene expression
      and how this affects angiogenesis, progression, and metastasis. Of particular
      importance are hypoxia-regulated transcription factors because they can modulate
      expression of countless different genes. Additional genes analyzed in some detail
      include those encoding angiogenic growth factors, factors controlling blood flow,
      and those involved in metastasis. Although hypoxia is generally perceived as a
      hindrance to cancer therapy, it is possibly exploitable because severe oxygen
      deficiency is tumor specific. Strategies aimed at using the presence of hypoxia
      in solid tumors include oxygen sensitive chemotherapy and gene therapy.

PMID- 9634498
TI  - Microdissection, microchip arrays, and molecular analysis of tumor cells (primary
      and metastases).
AB  - Advances in biotechnology and bioinformatics are offering promise for new
      breakthroughs in gene discovery and elucidation of gene function. At present,
      many candidate genes related to cancer pathogenesis have been identified in
      several types of human cancer, yet frequently their function remains elusive.
      This is particularly true as it relates to the progression of human cancer. This
      landscape could change dramatically, however, as technological innovations and
      improvements continue to revolutionize these fields. High-throughput molecular
      approaches are emerging, which may become accurate, automated, and cost
      effective. For example, DNA arrays on microchips are under development with
      numerous applications, including the ability to screen genes rapidly for
      mutations and to study patterns of gene expression on a large scale. Automated
      systems for microdissection and sequencing are also in their implementation
      stages. Commensurate with their integration and evolution, these information and
      technological tools have the potential to offer a more comprehensive
      understanding of multiple genetic and cellular alterations occurring during
      cancer initiation, development, and progression. Ultimately, this fundamental
      knowledge can provide strategies for intervention, prevention, and early
      diagnosis. This is a US government work. There are no restrictions on its use.

PMID- 9634499
TI  - Radiation dose response for subclinical metastases.
AB  - The development of adjuvant therapies for subclinical metastases has been
      empiric. Decades of experience showed that 45 to 50 Gy resulted in high control
      rates for subclinical lymph node involvement.1 By analogy with the response of
      macroscopic tumors, in which doses below a threshold yield no benefit, it was
      commonly believed that doses lower than 40 to 50 Gy would not be useful in
      elective treatment of subclinical disease. Biological phenomena, such as presumed
      metastatic tumor cell burden and growth rate of micrometastases, which could
      guide the oncologist, had little or no role in the empirical development of
      adjuvant cytotoxic therapies. In this article, some assumptions regarding the
      biology of subclinical metastases are discussed and examined in the light of
      treatment responses reported from clinical experience. In particular, the
      importance of early initiation of adjuvant therapy can be appreciated as well as
      the significant reductions in the incidence of metastases that can be achieved
      even when doses less than 45 to 50 Gy have to be accepted if necessitated by
      normal tissue tolerance.

PMID- 9634500
TI  - Linkage analysis of human leukocyte antigen (HLA) markers in familial psoriasis:
      strong disequilibrium effects provide evidence for a major determinant in the HLA
      B/-C region.
AB  - Although psoriasis is strongly associated with certain human leukocyte antigens
      (HLAs), evidence for linkage to HLA markers has been limited. The objectives of
      this study were (1) to provide more definitive evidence for linkage of psoriasis
      to HLA markers in multiplex families; (2) to compare the major HLA risk alleles
      in these families with those determined by previous case-control studies; and (3)
      to localize the gene more precisely. By applying the transmission/disequilibrium
      test (TDT) and parametric linkage analysis, we found evidence for linkage of
      psoriasis to HLA-C, -B, -DR, and -DQ, with HLA-B and -C yielding the most
      significant results. Linkage was detectable by parametric methods only when
      marker-trait disequilibrium was considered. Case-control association tests and
      the TDT identified alleles belonging to the EH57.1 ancestral haplotype as the
      major risk alleles in our sample. Among individuals carrying recombinant
      ancestral haplotypes involving EH57. 1, the class I markers were retained
      selectively among affecteds four times more often than among unaffecteds; among
      the few affected individuals carrying only the class II alleles from the
      ancestral haplotype, all but one also carried Cw6. These data show that familial
      and "sporadic" psoriasis share the same risk alleles. They also illustrate that
      substantial parametric linkage information can be extracted by accounting for
      linkage disequilibrium. Finally, they strongly suggest that a major
      susceptibility gene resides near HLA-C.

PMID- 9634501
TI  - Direct evidence for suppression of recombination within two pericentric
      inversions in humans: a new sperm-FISH technique.
AB  - Crossover within a pericentric inversion produces reciprocal recombinant
      chromosomes that are duplicated/deficient for all chromatin distal to the
      breakpoints. In view of this fact, a new technique is presented for estimating
      the frequency of recombination within pericentric inversions. YAC probes were
      selected from within the q- and p-arm flanking regions of two human inversions,
      and two-color FISH analysis was performed on sperm from heterozygous inversion
      carriers. A total of 6,006 sperm were analyzed for chromosome 1 inversion
      (p31q12), and 3,168 were analyzed for chromosome 8 inversion (p23q22). Both
      inversions displayed suppression of crossing-over, although the amount of
      suppression differed between the two inversions. The recombination frequency of
      13.1% recorded for chromosome 8 inversion was similar to the frequency of 11.4%
      previously estimated by the human/hamster-fusion method. For chromosome 1
      inversion, the recombination frequency of 0. 4% reported here was below the
      limits of detection of the fusion technique. The simplicity of the FISH technique
      and the ease of scoring facilitate analysis of a sample-population size much
      larger than previously had been possible.

PMID- 9634502
TI  - Genetic association of apolipoprotein E with age-related macular degeneration.
AB  - Age-related macular degeneration (AMD) is the most common geriatric eye disorder
      leading to blindness and is characterized by degeneration of the neuroepithelium
      in the macular area of the eye. Apolipoprotein E (apoE), the major apolipoprotein
      of the CNS and an important regulator of cholesterol and lipid transport, appears
      to be associated with neurodegeneration. The apoE gene (APOE) polymorphism is a
      strong risk factor for various neurodegenerative diseases, and the apoE protein
      has been demonstrated in disease-associated lesions of these disorders.
      Hypothesizing that variants of APOE act as a potential risk factor for AMD, we
      performed a genetic-association study among 88 AMD cases and 901 controls derived
      from the population-based Rotterdam Study in the Netherlands. The APOE
      polymorphism showed a significant association with the risk for AMD; the APOE
      epsilon4 allele was associated with a decreased risk (odds ratio 0.43 [95%
      confidence interval 0.21-0. 88]), and the epsilon2 allele was associated with a
      slightly increased risk of AMD (odds ratio 1.5 [95% confidence interval 0.8-2.
      82]). To investigate whether apoE is directly involved in the pathogenesis of
      AMD, we studied apoE immunoreactivity in 15 AMD and 10 control maculae and found
      that apoE staining was consistently present in the disease-associated deposits in
      AMD-maculae-that is, drusen and basal laminar deposit. Our results suggest that
      APOE is a susceptibility gene for AMD.

PMID- 9634503
TI  - Alternative interpretation of reported paracentric inversion.

PMID- 9634505
TI  - PedCheck: a program for identification of genotype incompatibilities in linkage
      analysis.
AB  - Prior to performance of linkage analysis, elimination of all Mendelian
      inconsistencies in the pedigree data is essential. Often, identification of
      erroneous genotypes by visual inspection can be very difficult and time
      consuming. In fact, sometimes the errors are not recognized until the stage of
      running linkage-analysis software. The effort then required to find the erroneous
      genotypes and to cross-reference pedigree and marker data that may have been
      recoded and renumbered can be not only tedious but also quite daunting, in the
      case of very large pedigrees. We have implemented four error-checking algorithms
      in a new computer program, PedCheck, which will assist researchers in identifying
      all Mendelian inconsistencies in pedigree data and will provide them with useful
      and detailed diagnostic information to help resolve the errors. Our program,
      which uses many of the algorithms implemented in VITESSE, handles large data sets
      quickly and efficiently, accepts a variety of input formats, and offers various
      error-checking algorithms that match the subtlety of the pedigree error. These
      algorithms range from simple parent-offspring-compatibility checks to a single
      locus likelihood-based statistic that identifies and ranks the individuals most
      likely to be in error. We use various real data sets to illustrate the power and
      effectiveness of our program.

PMID- 9634504
TI  - Frequency and carrier risk associated with common BRCA1 and BRCA2 mutations in
      Ashkenazi Jewish breast cancer patients.
AB  - Based on breast cancer families with multiple and/or early-onset cases, estimates
      of the lifetime risk of breast cancer in carriers of BRCA1 or BRCA2 mutations may
      be as high as 85%. The risk for individuals not selected for family history or
      other risk factors is uncertain. We determined the frequency of the common BRCA1
      (185delAG and 5382insC) and BRCA2 (6174delT) mutations in a series of 268
      anonymous Ashkenazi Jewish women with breast cancer, regardless of family history
      or age at onset. DNA was analyzed for the three mutations by allele-specific
      oligonucleotide hybridization. Eight patients (3.0%, 95% confidence interval [CI]
      1.5%-5.8%) were heterozygous for the 185delAG mutation, two (0.75%, 95% CI 0.20
      2.7) for the 5382insC mutation, and eight (3.0%, 95% CI 1.5-5.8) for the 6174delT
      mutation. The lifetime risk for breast cancer in Ashkenazi Jewish carriers of the
      BRCA1 185delAG or BRCA2 6174delT mutations was calculated to be 36%,
      approximately three times the overall risk for the general population (relative
      risk 2.9, 95% CI 1.5-5.8). For the 5382insC mutation, because of the low number
      of carriers found, further studies are necessary. The results differ markedly
      from previous estimates based on high-risk breast cancer families and are
      consistent with lower estimates derived from a recent population-based study in
      the Baltimore area. Thus, presymptomatic screening and counseling for these
      common mutations in Ashkenazi Jewish women not selected for family history of
      breast cancer should be reconsidered until the risk associated with these
      mutations is firmly established, especially since early diagnostic and preventive
      treatment modalities are limited.

PMID- 9634506
TI  - Localization of a gene (CORD7) for a dominant cone-rod dystrophy to chromosome
      6q.

PMID- 9634507
TI  - Sequence homology between 4qter and 10qter loci facilitates the instability of
      subtelomeric KpnI repeat units implicated in facioscapulohumeral muscular
      dystrophy.
AB  - Physical mapping and in situ hybridization experiments have shown that a
      duplicated locus with a structural organization similar to that of the 4q35 locus
      implicated in facioscapulohumeral muscular dystrophy is present in the
      subtelomeric portion of 10q. We performed sequence analysis of the p13E-11 probe
      and of the adjacent KpnI tandem-repeat unit derived from a 10qter cosmid clone
      and compared our results with those published, by other laboratories, for the
      4q35 region. We found that the sequence homology range is 98%-100% and confirmed
      that the only difference that can be exploited for differentiation of the 10qter
      from the 4q35 alleles is the presence of an additional BlnI site within the
      10qter KpnI repeat unit. In addition, we observed that the high degree of
      sequence homology does facilitate interchromosomal exchanges resulting in
      displacement of the whole set of BlnI-resistant or BlnI-sensitive KpnI repeats
      from one chromosome to the other. However, partial translocations escape
      detection if the latter simply relies on the hybridization pattern from double
      digestion with EcoRI/BlnI and with p13E-11 as a probe. We discovered that the
      restriction enzyme Tru9I cuts at both ends of the array of KpnI repeats of
      different chromosomal origins and allows the use of cloned KpnI sequences as a
      probe by eliminating other spurious fragments. This approach coupled with BlnI
      digestion permitted us to investigate the structural organization of BlnI
      resistant and BlnI-sensitive units within translocated chromosomes of 4q35 and
      10q26 origin. A priori, the possibility that partial translocations could play a
      role in the molecular mechanism of the disease cannot be excluded.

PMID- 9634508
TI  - Evidence that a locus for familial high myopia maps to chromosome 18p.
AB  - Myopia, or nearsightedness, is the most common human eye disorder. A genomewide
      screen was conducted to map the gene(s) associated with high, early-onset,
      autosomal dominant myopia. Eight families that each included two or more
      individuals with >=-6.00 diopters (D) myopia, in two or more successive
      generations, were identified. Myopic individuals had no clinical evidence of
      connective-tissue abnormalities, and the average age at diagnosis of myopia was
      6.8 years. The average spherical component refractive error for the affected
      individuals was -9.48 D. The families contained 82 individuals; of these, DNA was
      available for 71 (37 affected). Markers flanking or intragenic to the genes for
      Stickler syndrome types 1 and 2 (chromosomes 12q13.1-q13.3 and 6p21.3,
      respectively), Marfan syndrome (chromosome 15q21.1), and juvenile glaucoma
      (chromosome 1q21-q31) were also analyzed. No evidence of linkage was found for
      markers for the Stickler syndrome types 1 and 2, the Marfan syndrome, or the
      juvenile glaucoma loci. After a genomewide search, evidence of significant
      linkage was found on chromosome 18p. The maximum LOD score was 9.59, with marker
      D18S481, at a recombination fraction of .0010. Haplotype analysis further refined
      this myopia locus to a 7.6-cM interval between markers D18S59 and D18S1138 on
      18p11.31.

PMID- 9634509
TI  - Mapping genes that underlie ethnic differences in disease risk: methods for
      detecting linkage in admixed populations, by conditioning on parental admixture.
AB  - Genes that underlie ethnic differences in disease risk can be mapped in affected
      individuals of mixed descent if the ancestry of the alleles at each marker locus
      can be assigned to one of the two founding populations. Linkage can be detected
      by testing for association of the disease with the ancestry of alleles at the
      marker locus, by conditioning on the admixture (defined as the proportion of
      genes that have ancestry from the high-risk population) of both parents. With
      regard to exploiting the effects of admixture, this test is more flexible and
      powerful than the transmission-disequilibrium test. Under the assumption of a
      multiplicative model, the statistical power for a given sample size depends only
      on parental admixture and the risk ratio r between populations that is generated
      by the locus. The most informative families are those in which mean parental
      admixture is .2-.7 and in which admixture is similar in both parents. The number
      of markers required for a genome search depends on the number of generations
      since admixture and on the information content for ancestry (f) of the markers,
      defined as a function of allele frequencies in the two founding populations.
      Simulations using a hidden Markov model suggest that, when admixture has occurred
      2-10 generations earlier, a multipoint analysis using 2,000 biallelic markers,
      with f values of 30%, can extract 70%-90% of the ancestry information for each
      locus. Sets of such markers could be selected from libraries of single-nucleotide
      polymorphisms, when these become available.

PMID- 9634510
TI  - Mapping of complex traits by single-nucleotide polymorphisms.
AB  - Molecular geneticists are developing the third-generation human genome map with
      single-nucleotide polymorphisms (SNPs), which can be assayed via chip-based
      microarrays. One use of these SNP markers is the ability to locate loci that may
      be responsible for complex traits, via linkage/linkage-disequilibrium analysis.
      In this communication, we describe a semiparametric method for combined
      linkage/linkage-disequilibrium analysis using SNP markers. Asymptotic results are
      obtained for the estimated parameters, and the finite-sample properties are
      evaluated via a simulation study. We also applied this technique to a simulated
      genome-scan experiment for mapping a complex trait with two major genes. This
      experiment shows that separate linkage and linkage-disequilibrium analyses
      correctly detected the signals of both major genes; but the rates of false
      positive signals seem high. When linkage and linkage-disequilibrium signals were
      combined, the analysis yielded much stronger and clearer signals for the presence
      of two major genes than did two separate analyses.

PMID- 9634511
TI  - Cytochrome c oxidase deficiency associated with the first stop-codon point
      mutation in human mtDNA.
AB  - We have identified the first stop-codon point mutation in mtDNA to be reported in
      association with human disease. A 36-year-old woman experienced episodes of
      encephalopathy accompanied by lactic acidemia and had exercise intolerance and
      proximal myopathy. Histochemical analysis showed that 90% of muscle fibers
      exhibited decreased or absent cytochrome c oxidase (COX) activity. Biochemical
      studies confirmed a severe isolated reduction in COX activity. Muscle
      immunocytochemistry revealed a pattern suggestive of a primary mtDNA defect in
      the COX-deficient fibers and was consistent with either reduced stability or
      impaired assembly of the holoenzyme. Sequence analysis of mtDNA identified a
      novel heteroplasmic G-->A point mutation at position 9952 in the patient's
      skeletal muscle, which was not detected in her leukocyte mtDNA or in that of 120
      healthy controls or 60 additional patients with mitochondrial disease. This point
      mutation is located in the 3' end of the gene for subunit III of COX and is
      predicted to result in the loss of the last 13 amino acids of the highly
      conserved C-terminal region of this subunit. It was not detected in mtDNA
      extracted from leukocytes, skeletal muscle, or myoblasts of the patient's mother
      or her two sons, indicating that this mutation is not maternally transmitted.
      Single-fiber PCR studies provided direct evidence for an association between this
      point mutation and COX deficiency and indicated that the proportion of mutant
      mtDNA required to induce COX deficiency is lower than that reported for tRNA-gene
      point mutations. The findings reported here represent only the second case of
      isolated COX deficiency to be defined at the molecular genetic level and reveal a
      new mutational mechanism in mitochondrial disease.

PMID- 9634512
TI  - Evidence for linkage of human primary systemic carnitine deficiency with D5S436:
      a novel gene locus on chromosome 5q.
AB  - Primary systemic carnitine deficiency (SCD) is a rare hereditary disorder
      transmitted by an autosomal recessive mode of inheritance. The disorder includes
      cardiomyopathy, muscle weakness, hypoketotic coma with hypoglycemia, and
      hyperammonemia. In this study, we conducted a linkage analysis of a Japanese SCD
      family with a proband-a 9-year-old girl-and 26 members. The serum and urinary
      carnitine levels were determined for all members. The entire genome was searched
      for linkage to the gene locus for SCD, by use of a total of approximately 300
      polymorphic markers located approximately 15-20 cM apart. In the family, there
      were two significantly different phenotypes, in terms of serum free-carnitine
      levels: low serum free-carnitine level (29.5+/-5.0 microM; n=14) and normal serum
      free-carnitine level (46.8+/-6.2 microM; n=12). There was no correlation of
      urinary free-carnitine levels with the low serum-level phenotype (putative
      heterozygote), but in normal phenotypes (wild type) urinary levels decreased as
      the serum levels decreased; renal resorption of free carnitine appeared to be
      complete in wild-type individuals, when the serum free-carnitine level was <36
      microM. Linkage analysis using an autosomal dominant mode of inheritance of
      heterozygosity revealed a tight linkage between the disease allele and D5S436 on
      chromosome 5q, with a two-point LOD score of 4.98 and a multipoint LOD score of
      5.52. The haplotype analysis revealed that the responsible genetic locus lies
      between D5S658 and D5S434, which we named the "SCD" locus. This region was
      syntenic with the jvs locus, which is responsible for murine SCD. Phylogenic
      conversion of the SCD locus strongly suggests involvement of a single gene, in
      human SCD.

PMID- 9634513
TI  - Homozygosity and linkage-disequilibrium mapping of the syndrome of congenital
      hypoparathyroidism, growth and mental retardation, and dysmorphism to a 1-cM
      interval on chromosome 1q42-43.
AB  - The syndrome of hypoparathyroidism associated with growth retardation,
      developmental delay, and dysmorphism (HRD) is a newly described, autosomal
      recessive, congenital disorder with severe, often fatal consequences. Since the
      syndrome is very rare, with all parents of affected individuals being
      consanguineous, it is presumed to be caused by homozygous inheritance of a single
      recessive mutation from a common ancestor. To localize the HRD gene, we performed
      a genomewide screen using DNA pooling and homozygosity mapping for apparently
      unlinked kindreds. Analysis of a panel of 359 highly polymorphic markers revealed
      linkage to D1S235. The maximum LOD score obtained was 4.11 at a recombination
      fraction of 0. Analysis of three additional markers-GGAA6F06, D1S2678, and D1S179
      in a 2-cM interval around D1S235 resulted in LOD scores >3. Analysis of
      additional chromosome 1 markers revealed evidence of genetic linkage
      disequilibrium and place the HRD locus within an approximately 1-cM interval
      defined by D1S1540 and D1S2678 on chromosome 1q42-43.

PMID- 9634514
TI  - Localization of a gene for molybdenum cofactor deficiency, on the short arm of
      chromosome 6, by homozygosity mapping.
AB  - Molybdenum cofactor deficiency (MoCoD) is a fatal disorder manifesting, shortly
      after birth, with profound neurological abnormalities, mental retardation, and
      severe seizures unresponsive to any therapy. The disease is a monogenic,
      autosomal recessive disorder, and the existence of at least two complementation
      groups suggests genetic heterogeneity. In humans, MoCoD leads to the combined
      deficient activities of sulfite oxidase, xanthine dehydrogenase, and aldehyde
      oxidase. By using homozygosity mapping and two consanguineous affected kindreds
      of Israeli-Arab origin, including five patients, we demonstrated linkage of a
      MoCoD gene to an 8-cM region on chromosome 6p21.3, between markers D6S1641 and
      D6S1672. Linkage analysis generated the highest combined LOD-score value, 3.6, at
      a recombination fraction of 0, with marker D6S1575. These results now can be used
      to perform prenatal diagnosis with microsatellite markers. They also provide the
      only tool for carrier detection of this fatal disorder.

PMID- 9634515
TI  - Acromesomelic dysplasia Maroteaux type maps to human chromosome 9.
AB  - Acromesomelic dysplasias are skeletal disorders that disproportionately affect
      the middle and distal segments of the appendicular skeleton. We report genetic
      mapping studies in four families with acromesomelic dysplasia Maroteaux type
      (AMDM), an autosomal recessive osteochondrodysplasia. A peak LOD score of 5.1 at
      recombination fraction 0 was obtained with fully informative markers on human
      chromosome 9. In three of the four families, the affected offspring are products
      of consanguineous marriages; if it is assumed that these affected offspring are
      homozygous by descent for the region containing the AMDM locus, a 6.9-cM AMDM
      candidate interval can be defined by markers D9S1853 and D9S1874. The mapping of
      the AMDM locus to human chromosome 9 indicates that AMDM is genetically distinct
      from the two other mapped acromesomelic dysplasias, Hunter-Thompson type and
      Grebe type, which are caused by mutations in CDMP1 on human chromosome 20.

PMID- 9634516
TI  - Maternal mosaicism for a second mutational event in a type I spinal muscular
      atrophy family.
AB  - Spinal muscular atrophy (SMA) is a common fatal motor-neuron disorder
      characterized by degeneration of the anterior horn cells of the spinal cord,
      which results in proximal muscle weakness. Three forms of the disease, exhibiting
      differing phenotypic severity, map to chromosome 5q13 in a region of unusually
      high genomic variability. The SMA-determining gene (SMN) is deleted or rearranged
      in patients with SMA of all levels of severity. A high de novo mutation rate has
      been estimated for SMA, based on the deletion of multicopy microsatellite
      markers. We present a type I SMA family in which a mutant SMA chromosome has
      undergone a second mutation event. Both the occurrence of three affected siblings
      harboring this same mutation in one generation of this family and the obligate
      carrier status of their mother indicate the existence of maternal germ-line
      mosaicism for cells carrying the second mutation. The existence of secondary
      mutational events and of germ-line mosaicism has implications for the counseling
      of SMA families undergoing prenatal genetic analysis.

PMID- 9634517
TI  - Evidence for linkage of spelling disability to chromosome 15.

PMID- 9634518
TI  - A European multicenter study of phenylalanine hydroxylase deficiency:
      classification of 105 mutations and a general system for genotype-based
      prediction of metabolic phenotype.
AB  - Phenylketonuria (PKU) and mild hyperphenylalaninemia (MHP) are allelic disorders
      caused by mutations in the gene encoding phenylalanine hydroxylase (PAH).
      Previous studies have suggested that the highly variable metabolic phenotypes of
      PAH deficiency correlate with PAH genotypes. We identified both causative
      mutations in 686 patients from seven European centers. On the basis of the
      phenotypic characteristics of 297 functionally hemizygous patients, 105 of the
      mutations were assigned to one of four arbitrary phenotype categories. We
      proposed and tested a simple model for correlation between genotype and
      phenotypic outcome. The observed phenotype matched the predicted phenotype in 79%
      of the cases, and in only 5 of 184 patients was the observed phenotype more than
      one category away from that expected. Among the seven contributing centers, the
      proportion of patients for whom the observed phenotype did not match the
      predicted phenotype was 4%-23% (P<.0001), suggesting that differences in methods
      used for mutation detection or phenotype classification may account for a
      considerable proportion of genotype-phenotype inconsistencies. Our data indicate
      that the PAH-mutation genotype is the main determinant of metabolic phenotype in
      most patients with PAH deficiency. In the present study, the classification of
      105 PAH mutations may allow the prediction of the biochemical phenotype in
      >10,000 genotypes, which may be useful for the management of
      hyperphenylalaninemia in newborns.

PMID- 9634519
TI  - Localization of a multiple synostoses-syndrome disease gene to chromosome 17q21
      22.
AB  - Multiple synostoses syndrome is an autosomal dominant disorder characterized by
      premature onset of joint fusions, which initially affect the interphalangeal
      joints, by characteristic facies, and by deafness. We performed linkage analysis
      on a large Hawaiian family with multiple synostoses syndrome. Because another
      autosomal dominant disorder, proximal symphalangism, shares some clinical
      symptoms with multiple synostoses syndrome and has been linked to markers at loci
      at chromosome 17q21-22, we tested the hypothesis that multiple synostoses
      syndrome is linked to the same chromosomal region. Using polymorphic markers from
      the proximal symphalangism interval, we conducted linkage analysis and showed
      that the multiple synostoses-syndrome phenotype is linked to the same chromosomal
      region. A maximum LOD score of 3.98 at recombination fraction of .00 was achieved
      for the marker at locus D17S787. Further genetic analysis identified individuals
      with recombinant genotypes, allowing localization of the disease gene within the
      interval D17S931-D17S792, a 16-cM region. These data provide evidence that
      multiple synostoses syndrome and proximal symphalangism may be allelic disorders.

PMID- 9634521
TI  - Anticipation in familial Hodgkin lymphoma.

PMID- 9634520
TI  - The spreading of X inactivation into autosomal material of an x;autosome
      translocation: evidence for a difference between autosomal and X-chromosomal DNA.
AB  - X inactivation involves initiation, propagation, and maintenance of genetic
      inactivation. Studies of replication timing in X;autosome translocations have
      suggested that X inactivation may spread into adjacent autosomal DNA. To examine
      the inactivation of autosomal material at the molecular level, we assessed the
      transcriptional activity of X-linked and autosomal loci spanning an inactive
      translocation in a phenotypically normal female with a karyotype of
      46,X,der(X)t(X;4)(q22;q24). Since 4q duplications usually manifest dysmorphic
      features and severe growth and mental retardation, the normal phenotype of this
      individual suggested the spreading of X inactivation throughout the autosomal
      material. Consistent with this model, reverse transcription-PCR analysis of 20
      transcribed sequences spanning 4q24-qter revealed that three known genes and 11
      expressed sequence tags (ESTs) were not expressed in a somatic-cell hybrid that
      carries the translocation chromosome. However, three ESTs and three known genes
      were expressed from the t(X;4) chromosome and thus "escaped" X inactivation. This
      direct assay of expression demonstrated that the spreading of inactivation from
      the adjoining X chromosome was incomplete and noncontiguous. These findings are
      broadly consistent with the existence of genes known to escape inactivation on
      normal inactive X chromosomes. However, the fact that a high proportion (30%) of
      tested autosomal genes escaped inactivation may indicate that autosomal material
      lacks X chromosome-specific features that are associated with the spreading
      and/or maintenance of inactivation.

PMID- 9634522
TI  - The 8765delAG mutation in BRCA2 is common among Jews of Yemenite extraction.

PMID- 9634524
TI  - Muir-Torre phenotype has a frequency of DNA mismatch-repair-gene mutations
      similar to that in hereditary nonpolyposis colorectal cancer families defined by
      the Amsterdam criteria.
AB  - Muir-Torre syndrome (MTS) is an autosomal dominant disease defined by the
      coincidence of at least one sebaceous skin tumor and one internal malignancy.
      About half of MTS patients are affected by colorectal cancer. In a subgroup of
      MTS patients the disease has an underlying DNA mismatch-repair (MMR) defect and
      thus is allelic to hereditary nonpolyposis colorectal cancer (HNPCC). The purpose
      of this study was to examine to what extent germ-line mutations in DNA MMR genes
      are the underlying cause of the MTS phenotype. We ascertained 16 MTS patients
      with sebaceous skin tumors and colorectal cancer, and we examined their skin and
      visceral tumors for microsatellite instability. All the patients exhibited high
      genomic instability in at least one tumor. The search for germ-line mutations in
      the hMSH2 and hMLH1 genes in 13 of the MTS patients revealed truncating mutations
      in 9 (69%): eight mutations in the hMSH2 gene and one in the hMLH1 gene. This is
      the first systematic search for germ-line mutations in patients ascertained on
      the basis of sebaceous skin tumors. Our results indicate that (1) MTS patients
      exhibit significantly more mutations in the hMSH2 gene than in the hMLH1 gene;
      and (2) the subpopulation of MTS patients who are also affected by colorectal
      cancer, irrespective of family history and age at onset of tumors, may have a
      likelihood for an underlying DNA MMR defect similar to that for patients with a
      family history fulfilling the strict clinical criteria for HNPCC.

PMID- 9634523
TI  - A gene for autosomal recessive limb-girdle muscular dystrophy in Manitoba
      Hutterites maps to chromosome region 9q31-q33: evidence for another limb-girdle
      muscular dystrophy locus.
AB  - Characterized by proximal muscle weakness and wasting, limb-girdle muscular
      dystrophies (LGMDs) are a heterogeneous group of clinical disorders. Previous
      reports have documented either autosomal dominant or autosomal recessive modes of
      inheritance, with genetic linkage studies providing evidence for the existence of
      at least 12 distinct loci. Gene products have been identified for five genes
      responsible for autosomal recessive forms of the disorder. We performed a genome
      scan using pooled DNA from a large Hutterite kindred in which the affected
      members display a mild form of autosomal recessive LGMD. A total of 200 markers
      were used to screen pools of DNA from patients and their siblings. Linkage
      between the LGMD locus and D9S302 (maximum LOD score 5.99 at recombination
      fraction .03) was established. Since this marker resides within the chromosomal
      region known to harbor the gene causing Fukuyama congenital muscular dystrophy
      (FCMD), we expanded our investigations, to include additional markers in
      chromosome region 9q31-q34.1. Haplotype analysis revealed five recombinations
      that place the LGMD locus distal to the FCMD locus. The LGMD locus maps close to
      D9S934 (maximum multipoint LOD score 7.61) in a region that is estimated to be
      approximately 4.4 Mb (Genetic Location Database composite map). On the basis of
      an inferred ancestral recombination, the gene may lie in a 300-kb region between
      D9S302 and D9S934. Our results provide compelling evidence that yet another gene
      is involved in LGMD; we suggest that it be named "LGMD2H."

PMID- 9634525
TI  - Fine localization of the Nijmegen breakage syndrome gene to 8q21: evidence for a
      common founder haplotype.
AB  - Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder
      characterized by microcephaly, a birdlike face, growth retardation,
      immunodeficiency, lack of secondary sex characteristics in females, and increased
      incidence of lymphoid cancers. NBS cells display a phenotype similar to that of
      cells from ataxia-telangiectasia patients, including chromosomal instability,
      radiation sensitivity, and aberrant cell-cycle-checkpoint control following
      exposure to ionizing radiation. A recent study reported genetic linkage of NBS to
      human chromosome 8q21, with strong linkage disequilibrium detected at marker
      D8S1811 in eastern European NBS families. We collected a geographically diverse
      group of NBS families and tested them for linkage, using an expanded panel of
      markers at 8q21. In this article, we report linkage of NBS to 8q21 in 6/7 of
      these families, with a maximum LOD score of 3.58. Significant linkage
      disequilibrium was detected for 8/13 markers tested in the 8q21 region, including
      D8S1811. In order to further localize the gene for NBS, we generated a radiation
      hybrid map of markers at 8q21 and constructed haplotypes based on this map.
      Examination of disease haplotypes segregating in 11 NBS pedigrees revealed
      recombination events that place the NBS gene between D8S1757 and D8S270. A common
      founder haplotype was present on 15/18 disease chromosomes from 9/11 NBS
      families. Inferred (ancestral) recombination events involving this common
      haplotype suggest that NBS can be localized further, to an interval flanked by
      markers D8S273 and D8S88.

PMID- 9634526
TI  - Inflation of sibling recurrence-risk ratio, due to ascertainment bias and/or
      overreporting.
AB  - One widely used measure of familial aggregation is the sibling recurrence-risk
      ratio, which is defined as the ratio of risk of disease manifestation, given that
      one's sibling is affected, as compared with the disease prevalence in the general
      population. Known as lambdaS, it has been used extensively in the mapping of
      complex diseases. In this paper, I show that, for a fictitious disease that is
      strictly nongenetic and nonenvironmental, lambdaS can be dramatically inflated
      because of misunderstanding of the original definition of lambdaS, ascertainment
      bias, and overreporting. Therefore, for a disease of entirely environmental
      origin, the lambdaS inflation due to ascertainment bias and/or overreporting is
      expected to be more prominent if the risk factor also is familially aggregated.
      This suggests that, like segregation analysis, the estimation of lambdaS also is
      prone to ascertainment bias and should be performed with great care. This is
      particularly important if one uses lambdaS for exclusion mapping, for
      discrimination between different genetic models, and for association studies,
      since these practices hinge tightly on an accurate estimation of lambdaS.

PMID- 9634527
TI  - Linkage and association between inflammatory bowel disease and a locus on
      chromosome 12.
AB  - Genetic epidemiological studies have shown that genetic factors are important in
      the pathogenesis of the idiopathic inflammatory bowel diseases (IBD), Crohn
      disease (CD), and ulcerative colitis (UC). A genome screen in the United Kingdom
      found linkage of IBD to a 41-cM region of chromosome 12, surrounding D12S83. We
      aimed to replicate this linkage and to narrow the region of interest.
      Nonparametric linkage analyses at microsatellites surrounding D12S83 were
      performed in 122 North American Caucasian families containing 208 genotyped IBD
      affected relative pairs. Transmission/disequilibrium tests (TDTs) were also
      performed. We confirmed that IBD is linked to chromosome 12 (peak GENEHUNTER-PLUS
      LOD* score 2.76 [P = .00016] between D12S1724 and D12S90). The evidence for
      linkage is contributed by both the group of CD-affected relative pairs (peak
      GENEHUNTER-PLUS LOD* score 1.79 [P = .0021] between D12S1724 and D12S90) and the
      group of UC-affected relative pairs (peak GENEHUNTER-PLUS LOD* score 1.82 [P =
      .0019] at D12S335). The TDT is positive at the D12S83 locus (global chi2 = 16.41,
      6 df, P = .012). In conclusion, we have independently confirmed linkage of IBD to
      the chromosome 12 region that we investigated. A positive TDT at D12S83 suggests
      that we have greatly narrowed the chromosome 12 region that contains an IBD
      locus.

PMID- 9634528
TI  - A new locus for autosomal recessive hereditary spastic paraplegia maps to
      chromosome 16q24.3.
AB  - Hereditary spastic paraplegia is a genetically and phenotypically heterogeneous
      disorder. Both pure and complicated forms have been described, with autosomal
      dominant, autosomal recessive, and X-linked inheritance. Various loci (SPG1-SPG6)
      associated with this disorder have been mapped. Here, we report linkage analysis
      of a large consanguineous family affected with autosomal recessive spastic
      paraplegia with age at onset of 25-42 years. Linkage analysis of this family
      excluded all previously described spastic paraplegia loci. A genomewide linkage
      analysis showed evidence of linkage to chromosome 16q24.3, with markers D16S413
      (maximum LOD score 3.37 at recombination fraction [theta] of .00) and D16S303
      (maximum LOD score 3.74 at straight theta=.00). Multipoint analysis localized the
      disease gene in the most telomeric region, with a LOD score of 4.2. These data
      indicate the presence of a new locus linked to pure recessive spastic paraplegia,
      on chromosome 16q24.3, within a candidate region of 6 cM.

PMID- 9634529
TI  - The Nova Scotia (type D) form of Niemann-Pick disease is caused by a G3097-->T
      transversion in NPC1.
AB  - Niemann-Pick type D (NPD) disease is a progressive neurodegenerative disorder
      characterized by the accumulation of tissue cholesterol and sphingomyelin. This
      disorder is relatively common in southwestern Nova Scotia, because of a founder
      effect. Our previous studies, using classic linkage analysis of this large
      extended kindred, defined the critical gene region to a 13-cM chromosome segment
      between D18S40 and D18S66. A recently isolated gene from this region, NPC1, is
      mutated in the majority of patients with Niemann-Pick type C disease. We have
      identified a point mutation within this gene (G3097-->T; Gly992-->Trp) that shows
      complete linkage disequilibrium with NPD, confirming that NPD is an allelic
      variant of NPC1.

PMID- 9634530
TI  - Pelizaeus-Merzbacher disease: identification of Xq22 proteolipid-protein
      duplications and characterization of breakpoints by interphase FISH.
AB  - Pelizaeus-Merzbacher disease (PMD) is an X-linked, dysmyelinating disorder of the
      CNS. Duplications of the proteolipid protein (PLP) gene have been found in a
      proportion of patients, suggesting that, in addition to coding-region or splice
      site mutations, overdosage of the gene can cause PMD. We show that the
      duplication can be detected by interphase FISH, using a PLP probe in five
      patients and their four asymptomatic carrier mothers. The extent of the
      duplication was analyzed in each family by interphase FISH, with probes from a 1.
      7-Mb region surrounding the PLP gene between markers DXS83 and DXS94. A large
      duplication >=500 kb was detected, with breakpoints that differed, between
      families, at the proximal end. Distinct separation of the duplicated PLP signals
      could be seen only on metaphase chromosomes in one family, providing further
      evidence that different duplication events are involved. Quantitative fluorescent
      multiplex PCR was used to confirm the duplication in patients, by the detection
      of increased copy number of the PLP gene. Multiallelic markers from the
      duplicated region were analyzed, since the identification of two alleles in an
      affected boy would indicate a duplication. The majority of boys were homozygous
      for all four markers, compared with their mothers, who were heterozygous for one
      to three of the markers. These results suggest that intrachromosomal
      rearrangements may be a common mechanism by which duplications arise in PMD. One
      boy was heterozygous for the PLP marker, indicating a duplication and suggesting
      that interchromosomal rearrangements of maternal origin also can be involved.
      Since duplications are a major cause of PMD, we propose that interphase FISH is a
      reliable method for diagnosis and identification of female carriers.

PMID- 9634531
TI  - Chromosome 6-linked autosomal recessive early-onset Parkinsonism: linkage in
      European and Algerian families, extension of the clinical spectrum, and evidence
      of a small homozygous deletion in one family. The French Parkinson's Disease
      Genetics Study Group, and the European Consortium on Genetic Susceptibility in
      Parkinson's Disease.
AB  - The gene for autosomal recessive juvenile Parkinsonism (AR-JP) recently has been
      mapped to chromosome 6q25.2-27 in Japanese families. We have tested one Algerian
      and 10 European multiplex families with early-onset Parkinson disease for linkage
      to this locus, with marker D6S305. Homogeneity analysis provided a conditional
      probability in favor of linkage of >.9 in eight families, which were analyzed
      further with eight microsatellite markers spanning the 17-cM AR-JP region.
      Haplotype reconstruction for eight families and determination of the smallest
      region of homozygosity in two consanguineous families reduced the candidate
      interval to 11.3 cM. If the deletion of two microsatellite markers (D6S411 and
      D6S1550) that colocalize on the genetic map and that segregate with the disease
      in the Algerian family is taken into account, the candidate region would be
      reduced to <1 cM. These findings should facilitate identification of the
      corresponding gene. We have confirmed linkage of AR-JP, in European families and
      in an Algerian family, to the PARK2 locus. PARK2 appears to be an important locus
      for AR-JP in European patients. The clinical spectrum of the disease in our
      families, with age at onset <=58 years and the presence of painful dystonia in
      some patients, is broader than that reported previously.

PMID- 9634532
TI  - Sporadic imprinting defects in Prader-Willi syndrome and Angelman syndrome:
      implications for imprint-switch models, genetic counseling, and prenatal
      diagnosis.
AB  - The Prader-Willi syndrome (PWS) and the Angelman syndrome (AS) are caused by the
      loss of function of imprinted genes in proximal 15q. In approximately 2%-4% of
      patients, this loss of function is due to an imprinting defect. In some cases,
      the imprinting defect is the result of a parental imprint-switch failure caused
      by a microdeletion of the imprinting center (IC). Here we describe the molecular
      analysis of 13 PWS patients and 17 AS patients who have an imprinting defect but
      no IC deletion. Heteroduplex and partial sequence analysis did not reveal any
      point mutations of the known IC elements, either. Interestingly, all of these
      patients represent sporadic cases, and some share the paternal (PWS) or the
      maternal (AS) 15q11-q13 haplotype with an unaffected sib. In each of five PWS
      patients informative for the grandparental origin of the incorrectly imprinted
      chromosome region and four cases described elsewhere, the maternally imprinted
      paternal chromosome region was inherited from the paternal grandmother. This
      suggests that the grandmaternal imprint was not erased in the father's germ line.
      In seven informative AS patients reported here and in three previously reported
      patients, the paternally imprinted maternal chromosome region was inherited from
      either the maternal grandfather or the maternal grandmother. The latter finding
      is not compatible with an imprint-switch failure, but it suggests that a paternal
      imprint developed either in the maternal germ line or postzygotically. We
      conclude (1) that the incorrect imprint in non-IC-deletion cases is the result of
      a spontaneous prezygotic or postzygotic error, (2) that these cases have a low
      recurrence risk, and (3) that the paternal imprint may be the default imprint.

PMID- 9634533
TI  - Mutations in the human sterol delta7-reductase gene at 11q12-13 cause Smith-Lemli
      Opitz syndrome.
AB  - The Smith-Lemli-Opitz syndrome (SLOS; also known as "RSH syndrome" [MIM 270400])
      is an autosomal recessive multiple malformation syndrome due to a defect in
      cholesterol biosynthesis. Children with SLOS have elevated serum 7
      dehydrocholesterol (7-DHC) levels and typically have low serum cholesterol
      levels. On the basis of this biochemical abnormality, it has been proposed that
      mutations in the human sterol Delta7-reductase (7-DHC reductase; E.C.1.3.1.21)
      gene cause SLOS. However, one could also propose a defect in a gene that encodes
      a protein necessary for either the expression or normal function of sterol Delta7
      reductase. We cloned cDNA encoding a human sterol Delta7-reductase (DHCR7) on the
      basis of its homology with the sterol Delta7-reductase from Arabidopsis thaliana,
      and we confirmed the enzymatic function of the human gene product by expression
      in SLOS fibroblasts. SLOS fibroblasts transfected with human sterol Delta7
      reductase cDNA showed a significant reduction in 7-DHC levels, compared with
      those in SLOS fibroblasts transfected with the vector alone. Using radiation
      hybrid mapping, we show that the DHCR7 gene is encoded at chromosome 11q12-13. To
      establish that defects in this gene cause SLOS, we sequenced cDNA clones from
      SLOS patients. In three unrelated patients we have identified four different
      mutant alleles. Our results demonstrate both that the cDNA that we have
      identified encodes the human sterol Delta7-reductase and that mutations in DHCR7
      are responsible for at least some cases of SLOS.

PMID- 9634534
TI  - Autosomal recessive juvenile parkinsonism maps to 6q25.2-q27 in four ethnic
      groups: detailed genetic mapping of the linked region.
AB  - Parkinson disease (PD) is a common neurodegenerative condition associated with
      degeneration of dopaminergic neurons in the zona compacta of the substantia
      nigra. There is increasing evidence that genetic factors play a role in the
      etiology of PD, although genetic heterogeneity is likely. An autosomal dominant
      syndrome with many similarities to sporadic PD has been mapped to 4q21-22 in a
      large Italian pedigree and has been found to be due to mutation of the alpha
      synuclein gene. However, this gene appears to account for only a minority of PD,
      and a susceptibility locus for autosomal dominant parkinsonism has recently been
      mapped, on 2p13. Autosomal recessive juvenile parkinsonism (JP), which shows
      marked clinical similarity to PD, maps to 6q25.2-q27. We found linkage to this
      region in a group of 15 families from four distinct ethnic backgrounds. A full
      genomic screen excluded other candidate regions. We have constructed a detailed
      genetic map of the linked region and have mapped the position of the manganese
      superoxide dismutase gene (SOD2). Recombination events restricted the JP locus to
      a 6.9-cM region and excluded SOD2. The apparent homozygosity for null alleles at
      D6S955 in one family suggested a deletion and finer localization of the JP locus.

PMID- 9634535
TI  - Host susceptibility to cancer progression.

PMID- 9634536
TI  - X-chromosome inactivation spreads itself: effects in autosomes.

PMID- 9634537
TI  - Pharmacogenetics of cancer therapy: getting personal.

PMID- 9634538
TI  - Nm23-H1: genetic alterations and expression patterns in tumor metastasis.

PMID- 9634539
TI  - CD44 isoform-cytoskeleton interaction in oncogenic signaling and tumor
      progression.
AB  - CD44, a major hyaluronan receptor, exists as several isoforms and is widely
      distributed in different cells and tissues. The isoforms of CD44, such as CD44s
      (the standard form), CD44E (the epithelial form) and CD44v (variant isoforms)
      (arise from differential splicing of one to ten (or eleven) variable exons that
      encode portions of the membrane proximal extracellular domain. The molecular
      diversity of CD44 isoforms is further compounded by differential biosynthetic
      processes and post-translational modifications [e.g. N-/O-glycosylation or
      glycosaminoglycan (GAG) addition]. This structural arrangement, which occurs
      within either the invariant region or the extracellular domain of the variant
      region, is important for CD44-mediated communication between extracellular matrix
      materials [ECM-hyaluronic acid (HA), collagen and fibronectin] and intracellular
      protein components (e.g cytoskeletal proteins and various regulatory enzymes).
      The 15 amino acid sequence [e.g. NSGNGAVEDRKPSGL (in human) or NGGNGTVEDRKPSEL
      (in mouse)] residing in the cytoplasmic domain of CD44 isoforms is the ankyrin
      binding domain of this family of transmembrane glycoproteins. Biochemical
      analyses plus in vitro mutagenesis indicate that the ankyrin-binding domain is
      required for CD44-mediated "outside-in" and "inside-out" cell activation events.
      Furthermore, CD44s-cytoskeleton interaction is tightly coupled with signal
      transducing molecules (e.g. p185HER2 or Src kinases) during oncogenic signaling.
      Moreover, the transmembrane linkage between CD44v isoforms (CD44v10 and CD44v3)
      and the cytoskeleton up-regulates invasive and metastatic-specific tumor
      phenotypes [e.g. matrix degradation (MMPs) activities, tumor cell invasion and
      migration]. These findings strongly suggest that the interaction between CD44
      isoforms and the cytoskeleton plays a pivotal role in the onset of oncogenesis
      and tumor progression.

PMID- 9634540
TI  - Plasticity of CD44s expression during progression and metastasis of fibrosarcoma
      in an animal model system.
AB  - CD44s (standard isoform), which binds hyaluronan (HA), has been analyzed for its
      significance during fibrosarcoma progression and metastasis in an athymic nude
      mouse model using Balb/c 3T3 cells transformed with ras or sis oncogenes. While
      ras (but not sis) transformation leads to upregulated expression of mouse CD44s
      and HA binding, transfection/overexpression of human CD44s gene (hCD44s) elicited
      remarkable plasticity of expression during progression and metastasis. In 3T3,
      hCD44s induced tumorigenesis, HA binding, and micrometastatic competence to lungs
      and other organs. In tumorigenic (but nonmetastatic) sis transformants or ras
      deleted revertants, it also induced micrometastatic competence. Conversely, large
      primary tumors and overt metastases lost hCD44s expression and HA binding via
      hypermethylation of hCD44s gene. Tail vein injections revealed that hCD44s
      greatly increased the efficiency of colonization of the lung microvasculature at
      the earliest stages. These studies indicate that hCD44s overexpression and
      possibly its HA binding are critical for conveying metastatic competence but are
      antagonistic or selected against during aggressive primary tumor or overt
      metastasis outgrowth. This remarkable plasticity of expression and its
      consequences offer an ideal system for dissecting the molecular mechanisms
      operating during fibrosarcoma progression and metastasis.

PMID- 9634541
TI  - Clinical implications of anomalous CD44 gene expression in neoplasia.
AB  - An intensive search continues for reliable markers that would be clinically
      useful in the diagnosis of small tumors and in the evaluation of their predicted
      clinical outcome. One potential marker, extensively studied in human samples is
      the cell surface adhesion molecule CD44. The single CD44 gene codes for a large
      family of cell surface proteins by alternative splicing and severe abnormalities
      have been observed in the patterns of its expression in many types of human
      tumors using both protein and RNA-based analyses. These abnormalities are
      manifested by markedly increased levels of unusual transcripts and proteins in
      tumor cells compared to the corresponding normal tissues. Aberrant processing of
      immature CD44 transcripts has also been observed in tumor cells and this can lead
      to the inappropriate retention of introns and to the use of cryptic splice sites
      in the mRNA. Inappropriate expression patterns of the alternatively spliced exons
      have also been linked both to tumor progression and to metastatic potential. The
      clinical relevance of all these observations is demonstrated by the frequent
      detection of these abnormalities in samples from malignant tumors of many
      different organs and by their presence in pre-invasive and high risk pre
      cancerous lesions. This article reviews the current information regarding the
      expression of the CD44 gene in tumor cells and its potential use as a marker in
      clinical evaluation. The overall conclusion is that with the use of the latest
      assay techniques and perhaps in combination with other molecular markers,
      analysis of CD44 expression can provide new and powerful assays for the detection
      of neoplastic disease.

PMID- 9634542
TI  - CD44 expression and growth factors.
AB  - Soluble factors such as growth factors and cytokines present in the tumor
      microenvironment regulate a variety of genes associated with malignant properties
      of tumor cells such as growth, migration, invasion, and metastatic capacities.
      CD44 is a multi-functional adhesion molecule involved in cell to cell and cell to
      extracellular matrix interaction, the trapping of growth factors and cytokines,
      and the regulation of cell traffic. Growth factors and cytokines modify the
      expression, selective isoform splicing and functions of CD44, resulting in
      changes in the biological properties of the cells. These include adhesion of
      circulating tumor cells to endothelium and body cavities, and survival in
      response to growth factors presented by the CD44 molecule. The modification of
      CD44 on both tumor and host cells by growth factors may play an important role in
      tumor progression.

PMID- 9634543
TI  - The role of CD44 as a cell surface hyaluronan receptor during tumor invasion of
      connective tissue.
AB  - Tumor progression involves a series of complex interactions between infiltrating
      malignant cells and adjacent normal tissues. The cell surface receptor CD44 has
      been implicated as an active participant in a number of these interactions.
      Although assigned a variety of functions, it is the role of CD44 as a receptor
      for the glycosaminoglycan hyaluronan that is likely to be of most importance. The
      matrix macromolecule hyaluronan often becomes deposited in the tissue spaces
      immediately surrounding invasive tumors. As such, hyaluronan may function as a
      ligand for CD44-mediated locomotion or assemble into a protective matrix coat
      surrounding the tumor cells. Alternatively, the adjacent hyaluronan-rich matrices
      may serve as a barrier to migration, breached in part by aggressive cell types
      exhibiting a capacity for CD44-mediated hyaluronan endocytosis. The significance
      of tumor-associated hyaluronan accumulation as well as potential functions of
      CD44--hyaluronan interactions are reviewed.

PMID- 9634544
TI  - CD44 structure and function.
AB  - In this review we discuss the structural elements of CD44 that have been shown to
      be involved in specific functions. To this end, we focus primarily on experiments
      in which CD44 constructs are transfected into cells whose function is then
      assayed. The hyaluronan binding function of CD44 has been assayed in cell lines
      and in fusion proteins, termed CD44-Igs, consisting of the external domain of
      CD44 coupled to the hinge, CH2 and CH3 regions of human IgG1. These studies have
      shown that hyaluronan binding by CD44 is regulated by the cells in which it is
      expressed, and that at least part of this regulation is determined by cell
      specific posttranslational modifications, especially N-glycosylation, of CD44
      itself. Variant isoforms of CD44 determined by alternative splicing of 11
      optional exons in the middle of the gene determine additional functions of CD44,
      as well as contributing to the regulation of hyaluronan binding. Soluble CD44 may
      modulate the function of cell surface CD44. The cytoplasmic domain of CD44
      contributes to ligand binding in a way that remains obscure. It also determines
      membrane localization in polarized epithelial cells, and is probably involved in
      CD44 interactions with the cytoskeleton and in mediating post-ligand binding
      events.

PMID- 9634546
TI  - Role of CD44 in CTL and NK cell activity.
AB  - CD44 is a widely distributed cell surface glycoprotein whose principal ligand has
      been identified as hyaluronic acid (HA), a major component of the extracellular
      matrix (ECM). Recent studies have demonstrated that activation through CD44 leads
      to induction of effector function in T cells and macrophages. At sites of chronic
      inflammation as seen in certain infections, autoimmune diseases, allograft
      rejection, graft-versus-host (GVH) disease and treatment of cancer patients with
      high doses of interleukin-2, significant damage to the endothelial cells has been
      known to occur, which leads to the toxicity or pathogenesis associated with the
      disease. The exact mechanism of endothelial cell damage is not clear, although,
      it has been widely speculated that immune cells may play a critical role. Studies
      from our laboratory have used interleukin-2 (IL-2) induced vascular leak syndrome
      (VLS) as a model to investigate the role of cytolytic lymphocytes in the direct
      cytotoxicity of endothelial cells. Cytotoxic T lymphocytes (CTL), double-negative
      (DN) T cells and natural killer (NK) cells upon activation express high levels of
      CD44 and mediate efficient MHC-unrestricted TCR-independent lysis following
      ligation of CD44. Such CD44-mediated cytotoxicity may play an important role in
      protection against viral infections and cancer. However, it could also cause non
      specific tissue injury. For example, dysregulation in the interaction between
      activated cytotoxic lymphocytes expressing CD44 and endothelial cells bearing the
      appropriated ligand such as the hyaluronate (HA), could lead to endothelial cell
      lysis. Furthermore, such endothelial cell injury could lead to the pathogenesis
      associated with a variety of clinical diseases.

PMID- 9634547
TI  - Identification of the amino terminus of neuronal Ca2+ channel alpha1 subunits
      alpha1B and alpha1E as an essential determinant of G-protein modulation.
AB  - We have examined the basis for G-protein modulation of the neuronal voltage
      dependent calcium channels (VDCCs) alpha1E and alpha1B. A novel PCR product of
      alpha1E was isolated from rat brain. This contained an extended 5' DNA sequence
      and was subcloned onto the previously cloned isoform rbEII, giving rise to
      alpha1Elong whose N terminus was extended by 50 amino acids. VDCC alpha1 subunit
      constructs were co-expressed with the accessory alpha2-delta and beta2a subunits
      in Xenopus oocytes and mammalian (COS-7) cells. The alpha1Elong showed
      biophysical properties similar to those of rbEII; however, when G-protein
      modulation of expressed alpha1 subunits was induced by activation of co-expressed
      dopamine (D2) receptors with quinpirole (100 nM) in oocytes, or by co
      transfection of Gbeta1gamma2 subunits in COS-7 cells, alpha1Elong, unlike
      alpha1E(rbEII), was found to be G-protein-modulated, in terms of both a slowing
      of activation kinetics and a reduction in current amplitude. However, alpha1Elong
      showed less modulation than alpha1B, and substitution of the alpha1E1-50 with the
      corresponding region of alpha1B1-55 produced a chimera alpha1bEEEE, with G
      protein modulation intermediate between alpha1Elong and alpha1B. Furthermore,
      deletion of the N-terminal 1-55 sequence from alpha1B produced alpha1BDeltaN1-55,
      which could not be modulated, thus identifying the N-terminal domain as essential
      for G-protein modulation. Taken together with previous studies, these results
      indicate that the intracellular N terminus of alpha1E1-50 and alpha1B1-55 is
      likely to contribute to a multicomponent site, together with the intracellular I
      II loop and/or the C-terminal tail, which are involved in Gbetagamma binding
      and/or in subsequent modulation of channel gating.

PMID- 9634548
TI  - Age-related changes in neuronal nicotinic acetylcholine receptor subunit alpha4
      expression are modified by long-term nicotine administration.
AB  - The distribution of the neuronal nicotinic acetylcholine receptor subunit alpha4
      (nAChRalpha4) in the brains of young (2-4 months) or aged (24-28 months) CBA/J
      mice was examined using immunohistochemical staining. Anti-nAChRalpha4
      immunoreactivity corresponded with nAChRalpha4 RNA expression and high-affinity
      [3H]nicotine binding. Immunostaining in aged mice relative to that in young
      animals was diminished in the medial septum and diagonal band but was unchanged
      in the globus pallidus and substantia nigra. The staining of neurons was almost
      completely absent in the hippocampus of aged animals. The oral administration of
      nicotine to aged animals for 6 weeks did not alter nAChRalpha4 expression
      relative to that in aged controls. However, the long-term delivery of nicotine
      (11 months) to 14-month-old animals corresponded with the highly specific
      preservation of nAChRalpha4 expression in some neurons of the dentate gyrus
      region and in neurite processes of remaining neurons of the hippocampal CA1
      region. These results support the conclusion that the loss of nAChRalpha4
      expression occurs in key cholinergic regions during normal aging. Furthermore,
      sustained long-term nicotine delivery may promote highly region-specific
      retention of nAChR expression, but only if initiated before normal age-related
      receptor decline.

PMID- 9634549
TI  - Isoform-specific regulation of the Na+/Ca2+ exchanger in rat astrocytes and
      neurons by PKA.
AB  - The Na+/Ca2+ exchanger is a major transporter of Ca2+ in neurons and glial cells.
      The Na+/Ca2+ exchanger gene NCX1 expresses tissue-specific isoforms of the
      Na+/Ca2+ exchanger, and the isoforms have been examined here quantitatively using
      primary cultures of astrocytes and neurons. We present a PCR-based quantitative
      method, quantitative end-labeled reverse transcription-PCR (QERT-PCR), to
      determine the relative amounts of the NCX1 isoforms present in these cells. Six
      exons (A, B, C, D, E, and F) are alternatively spliced to produce the known NCX1
      isoforms. Three exon B-containing isoforms (BDEF, BDF, and BD) are the
      predominant transcripts in primary rat cortical astrocytes and in C6 glioma
      cells. In contrast, exon A-containing isoforms (ADF and AD) are the predominant
      transcripts in primary rat hippocampal neurons. Functional differences between
      full-length constructs of NCX1 containing either the astrocyte isoform BD or the
      neuron isoform AD were examined in a Xenopus oocyte expression system. Although
      both isoforms function normally, the activity of the AD isoform can be increased
      39% by activation of protein kinase A (PKA), whereas that of the BD isoform is
      not affected. We conclude that specific NCX1 isoforms are expressed in distinct
      patterns in astrocytes and neurons. Furthermore, the activity of a neuronal (but
      not glial) isoform of the Na+/Ca2+ exchanger can be altered by the activation of
      the PKA pathway.

PMID- 9634550
TI  - On the action of the anti-absence drug ethosuximide in the rat and cat thalamus.
AB  - The action of ethosuximide (ETX) on Na+, K+, and Ca2+ currents and on tonic and
      burst-firing patterns was investigated in rat and cat thalamic neurons in vitro
      by using patch and sharp microelectrode recordings. In thalamocortical (TC)
      neurons of the rat dorsal lateral geniculate nucleus (LGN), ETX (0.75-1 mM)
      decreased the noninactivating Na+ current, INaP, by 60% but had no effect on the
      transient Na+ current. In TC neurons of the rat and cat LGN, the whole-cell
      transient outward current was not affected by ETX (up to 1 mM), but the sustained
      outward current was decreased by 39% at 20 mV in the presence of ETX (0.25-0.5
      mM): this reduction was not observed in a low Ca2+ (0.5 mM) and high Mg2+ (8 mM)
      medium or in the presence of Ni2+ (1 mM) and Cd2+ (100 microM). In addition, ETX
      (up to 1 mM) had no effect on the low-threshold Ca2+ current, IT, of TC neurons
      of the rat ventrobasal (VB) thalamus and LGN and in neurons of the rat nucleus
      reticularis thalami nor on the high-threshold Ca2+ current in TC neurons of the
      rat LGN. Sharp microelectrode recordings in TC neurons of the rat and cat LGN and
      VB showed that ETX did not change the resting membrane potential but increased
      the apparent input resistance at potentials greater than -60 mV, resulting in an
      increase in tonic firing. In contrast, ETX decreased the number of action
      potentials in the burst evoked by a low-threshold Ca2+ potential. The frequency
      of the remaining action potentials in a burst also was decreased, whereas the
      latency of the first action potential was increased. Similar effects were
      observed on the burst firing evoked during intrinsic delta oscillations. These
      results indicate an action of ETX on INaP and on the Ca2+-activated K+ current,
      which explains the decrease in burst firing and the increase in tonic firing,
      and, together with the lack of action on low- and high-threshold Ca2+ currents,
      the results cast doubts on the hypothesis that a reduction of IT in thalamic
      neurons underlies the therapeutic action of this anti-absence medicine.

PMID- 9634551
TI  - Quantitative evaluation of 5-hydroxytryptamine (serotonin) neuronal release and
      uptake: an investigation of extrasynaptic transmission.
AB  - Whether neurotransmitters are restricted to the synaptic cleft (participating
      only in hard-wired neurotransmission) or diffuse to remote receptor sites
      (participating in what has been termed volume or paracrine transmission) depends
      on a number of factors. These include (1) the location of release sites with
      respect to the receptors, (2) the number of molecules released, (3) the
      diffusional rate away from the release site, determined by both the geometry near
      the release site as well as binding interactions, and (4) the removal of
      transmitter by the relevant transporter. Fast-scan cyclic voltammetry allows for
      the detection of extrasynaptic concentrations of many biogenic amines, permitting
      direct access to many of these parameters. In this study the hypothesis that 5
      hydroxytryptamine (5-HT) transmission is primarily extrasynaptic in the
      substantia nigra reticulata, a terminal region with identified synaptic contacts,
      and the dorsal raphe nucleus, a somatodendritic region with rare synaptic
      incidence, was tested in brain slices prepared from the rat. Using carbon fiber
      microelectrodes, we found the concentration of 5-HT released per stimulus pulse
      in both regions to be identical when elicited by single pulse stimulations or
      trains at high frequency. 5-HT efflux elicited by a single stimulus pulse was
      unaffected by uptake inhibition or receptor antagonism. Thus, synaptic efflux is
      not restricted by binding to intrasynaptic receptors or transporters. The number
      of 5-HT molecules released per terminal was estimated in the substantia nigra
      reticulata and was considerably less than the number of 5-HT transporter and
      receptor sites, reinforcing the hypothesis that these sites are extrasynaptic.
      Furthermore, the detected extrasynaptic concentrations closely match the affinity
      for the predominant 5-HT receptor in each region. Although they do not disprove
      the existence of classical synaptic transmission, our results support the
      existence of paracrine neurotransmission in both serotonergic regions.

PMID- 9634552
TI  - Role of dopamine transporter in methamphetamine-induced neurotoxicity: evidence
      from mice lacking the transporter.
AB  - The role of the dopamine transporter (DAT) in mediating the neurotoxic effects of
      methamphetamine (METH) was tested in mice lacking DAT. Dopamine (DA) and
      serotonin (5-HT) content, glial fibrillary acidic protein (GFAP) expression, and
      free radical formation were assessed as markers of METH neurotoxicity in the
      striatum and/or hippocampus of wild-type, heterozygote, and homozygote (DAT -/-)
      mice. Four injections of METH (15 mg/kg, s.c.), each given 2 hr apart, produced
      80 and 30% decreases in striatal DA and 5-HT levels, respectively, in wild-type
      animals 2 d after administration. In addition, GFAP mRNA and protein expression
      levels, extracellular DA levels, and free radical formation were increased
      markedly. Hippocampal 5-HT content was decreased significantly as well (43%).
      Conversely, no significant changes were observed in total DA content, GFAP
      expression, extracellular DA levels, or free radical formation in the striatum of
      DAT -/- mice after METH administration. However, modest decreases were observed
      in striatal and hippocampal 5-HT levels (10 and 17%, respectively). These
      observations demonstrate that DAT is required for, and DA is an essential
      mediator of, METH-induced striatal dopaminergic neurotoxicity, whereas
      serotonergic deficits are only partially dependent on DAT.

PMID- 9634553
TI  - Evidence for metabotropic glutamate receptor activation in the induction of
      depolarization-induced suppression of inhibition in hippocampal CA1.
AB  - Depolarization-induced suppression of inhibition (DSI) is a transient reduction
      of GABAA receptor-mediated IPSCs that is mediated by a retrograde signal from
      principal cells to interneurons. Using whole-cell recordings, we tested the
      hypothesis that mGluRs are involved in the DSI process in hippocampal CA1, as has
      been proposed for cerebellar DSI. Group II mGluR agonists failed to affect either
      evoked monosynaptic IPSCs or DSI, and forskolin, which blocks cerebellar DSI, did
      not affect CA1 DSI. Group I and group III mGluR agonists reduced IPSCs, but only
      group I agonists occluded DSI. (S)-MCPG blocked (1S,3R)-ACPD-induced IPSC
      suppression and markedly reduced DSI, whereas group III antagonists had no effect
      on DSI. Many other similarities between DSI and the (1S,3R)-ACPD-induced
      suppression of IPSCs also were found. Our data suggest that a glutamate-like
      substance released from pyramidal cells could mediate CA1 DSI by reducing GABA
      release from interneurons via the activation of group I mGluRs.

PMID- 9634554
TI  - Ca2+ channel beta3 subunit enhances voltage-dependent relief of G-protein
      inhibition induced by muscarinic receptor activation and Gbetagamma.
AB  - The Ca2+ channel beta subunit has been shown to reduce the magnitude of G-protein
      inhibition of Ca2+ channels. However, neither the specificity of this action to
      different forms of G-protein inhibition nor the mechanism underlying this
      reduction in response is known. We have reported previously that coexpression of
      the Ca2+ channel beta3 subunit causes M2 muscarinic receptor-mediated inhibition
      of alpha1B Ca2+ currents to become more voltage-dependent. We report here that
      the beta3 subunit increases the rate of relief of inhibition produced by a
      depolarizing prepulse and also shifts the voltage dependency of this relief to
      more hyperpolarized voltages; these effects are likely to be responsible for the
      reduction of inhibitory response of alpha1B channels to G-protein-mediated
      inhibition seen after coexpression of the Ca2+ channel beta3 subunit.
      Additionally, the beta3 subunit alters the rate and voltage dependency of relief
      of the inhibition produced by coexpressed Gbeta1gamma1, in a manner similar to
      the changes it produces in relief of M2 receptor-induced inhibition. We conclude
      that the Ca2+ channel beta3 subunit reduces the magnitude of G-protein inhibition
      of alpha1B Ca2+ channels by enhancing the rate of dissociation of the G-protein
      betagamma subunit from the Ca2+ channel alpha1B subunit.

PMID- 9634555
TI  - Upregulation of the enzyme chain hydrolyzing extracellular ATP after transient
      forebrain ischemia in the rat.
AB  - A short ischemic period induced by the transient occlusion of major brain
      arteries induces neuronal damage in selectively vulnerable regions of the
      hippocampus. Adenosine is considered to be one of the major neuroprotective
      substances produced in the ischemic brain. It can be released from damaged cells,
      but it also could be generated extracellularly from released ATP via a surface
      located enzyme chain. Using the rat model of global forebrain ischemia, we
      applied a short (10 min) transient interruption of blood flow and studied the
      distribution of ectonucleotidase activities in the hippocampus. Northern
      hybridization of mRNA isolated from hippocampi of sham-operated and ischemic
      animals revealed an upregulation of ectoapyrase (capable of hydrolyzing
      nucleoside 5'-tri- and diphosphates) and ecto-5'-nucleotidase (capable of
      hydrolyzing nucleoside 5'-monophosphates). A histochemical analysis that used
      ATP, UTP, ADP, or AMP as substrates revealed a strong and selective increase in
      enzyme activity in the injured areas of the hippocampus. Enhanced staining could
      be observed first at 2 d. Staining increased within the next days and persisted
      at 28 d after ischemia. The spatiotemporal development of catalytic activities
      was identical for all substrates. It was most pronounced in the CA1 subfield and
      also could be detected in the dentate hilus and to a marginal extent in CA3. The
      histochemical staining corresponded closely to the development of markers for
      reactive glia, in particular of microglia. The upregulation of ectonucleotidase
      activities implies increased nucleotide release from the damaged tissue and could
      play a role in the postischemic control of nucleotide-mediated cellular
      responses.

PMID- 9634556
TI  - rMAL is a glycosphingolipid-associated protein of myelin and apical membranes of
      epithelial cells in kidney and stomach.
AB  - rMAL, the rat myelin and lymphocyte protein, is a small hydrophobic protein of 17
      kDa with four putative transmembrane domains and is expressed in oligodendrocytes
      and Schwann cells, the myelinating cells of the nervous system. In addition,
      transcript expression has been found in kidney, spleen, and intestine. Confocal
      microscopy and immunoelectron microscopy with an affinity-purified antibody
      localized rMAL to compact myelin in a pattern similar to the structural myelin
      proteins: myelin basic protein and proteolipid protein. In kidney and stomach
      epithelia, rMAL is located almost exclusively on the apical (luminal) membranes
      of the cells lining distal tubuli in kidney and the glandular part of the
      stomach. Biochemical analysis of plasma membranes isolated from spinal cord and
      kidney demonstrated that rMAL is a proteolipid that is present in detergent
      insoluble complexes typical for proteins associated with glycosphingolipids.
      Lipid and protein analysis showed a co-enrichment of glycosphingolipids and rMAL
      protein within these complexes, indicating a close association of rMAL to
      glycosphingolipids in myelin and in kidney in vivo. We conclude that specific
      rMAL-glycosphingolipid interactions may lead to the formation and maintenance of
      stable protein-lipid microdomains in myelin and apical epithelial membranes. They
      may contribute to specific properties of these highly specialized plasma
      membranes.

PMID- 9634557
TI  - Induction of caspase-3-like protease may mediate delayed neuronal death in the
      hippocampus after transient cerebral ischemia.
AB  - Delayed neuronal death after transient cerebral ischemia may be mediated, in
      part, by the induction of apoptosis-regulatory gene products. Caspase-3 is a
      newly characterized mammalian cysteine protease that promotes cell death during
      brain development, in neuronal cultures, and in other cell types under many
      different conditions. To determine whether caspase-3 serves to regulate neuronal
      death after cerebral ischemia, we have (1) cloned a cDNA encoding the rat brain
      caspase-3; (2) examined caspase-3 mRNA and protein expression in the brain using
      in situ hybridization, Northern and Western blot analyses, and double-labeled
      immunohistochemistry; (3) determined caspase-3-like activity in brain cell
      extracts; and (4) studied the effect of caspase-3 inhibition on cell survival and
      DNA fragmentation in the hippocampus in a rat model of transient global ischemia.
      At 8-72 hr after ischemia, caspase-3 mRNA and protein were induced in the
      hippocampus and caudate-putamen (CPu), accompanied by increased caspase-3-like
      protease activity. In the hippocampus, caspase-3 mRNA and protein were
      predominantly increased in degenerating CA1 pyramidal neurons. Proteolytic
      activation of the caspase-3 precursor was detected in hippocampus and CPu but not
      in cortex at 4-72 hr after ischemia. Double-label experiments detected DNA
      fragmentation in the majority of CA1 neurons and selective CPu neurons that
      overexpressed caspase-3. Furthermore, ventricular infusion of Z-DEVD-FMK, a
      caspase-3 inhibitor, decreased caspase-3 activity in the hippocampus and
      significantly reduced cell death and DNA fragmentation in the CA1 sector up to 7
      d after ischemia. These data strongly suggest that caspase-3 activity contributes
      to delayed neuronal death after transient ischemia.

PMID- 9634558
TI  - Neurturin exerts potent actions on survival and function of midbrain dopaminergic
      neurons.
AB  - Glial cell line-derived neurotrophic factor (GDNF) exhibits potent effects on
      survival and function of midbrain dopaminergic (DA) neurons in a variety of
      models. Although other growth factors expressed in the vicinity of developing DA
      neurons have been reported to support survival of DA neurons in vitro, to date
      none of these factors duplicate the potent and selective actions of GDNF in vivo.
      We report here that neurturin (NTN), a homolog of GDNF, is expressed in the
      nigrostriatal system, and that NTN exerts potent effects on survival and function
      of midbrain DA neurons. Our findings indicate that NTN mRNA is sequentially
      expressed in the ventral midbrain and striatum during development and that NTN
      exhibits survival-promoting actions on both developing and mature DA neurons. In
      vitro, NTN supports survival of embryonic DA neurons, and in vivo, direct
      injection of NTN into the substantia nigra protects mature DA neurons from cell
      death induced by 6-OHDA. Furthermore, administration of NTN into the striatum of
      intact adult animals induces behavioral and biochemical changes associated with
      functional upregulation of nigral DA neurons. The similarity in potency and
      efficacy of NTN and GDNF on DA neurons in several paradigms stands in contrast to
      the differential distribution of the receptor components GDNF Family Receptor
      alpha1 (GFRalpha1) and GFRalpha2 within the ventral mesencephalon. These results
      suggest that NTN is an endogenous trophic factor for midbrain DA neurons and
      point to the possibility that GDNF and NTN may exert redundant trophic influences
      on nigral DA neurons acting via a receptor complex that includes GFRalpha1.

PMID- 9634559
TI  - Immunohistochemical and cytochemical localization of the somatostatin receptor
      subtype sst1 in the somatostatinergic parvocellular neuronal system of the rat
      hypothalamus.
AB  - Somatostatin is known to mediate its actions through five G-protein-coupled
      receptors (sst1-sst5). We have studied the expression of the sst1 receptor in the
      rat hypothalamus by using a subtype-specific antiserum. In Western blotting, the
      antiserum reacted specifically with a band with an apparent molecular weight of
      80,000 in membranes prepared from hypothalamic tissue. The localization of the
      sst1 receptor was investigated by immunohistochemistry in hypothalamus sections.
      Additionally, an immunofluorescent double-labeling was performed for the sst1
      receptor and somatostatin. Light microscopy revealed that the sst1 receptor is
      located in perikarya and nerve fibers in the rostral periventricular area
      surrounding the third ventricle as well as in nerve fibers projecting from the
      perikarya to the external layer of the median eminence. In these neuronal
      structures, sst1 immunoreactivity was found to be colocalized with somatostatin.
      Furthermore, the location of sst1 receptors was studied by immunoelectron
      microscopy in the median eminence. In the external layer, receptor
      immunoreactivity was confined to nerve terminals. Immunoreactive nerve terminals
      were seen to make synapse-like junctions with other both stained and unstained
      nerve terminals. Thus, the sst1 receptor is present in the classic
      somatostatinergic hypothalamic parvocellular system inhibiting hormone secretion
      from the anterior pituitary gland. These findings indicate that the sst1 receptor
      may act as an autoreceptor and inhibit the release of somatostatin from
      periventricular neurons projecting to the median eminence.

PMID- 9634560
TI  - Acetylcholine triggers L-glutamate exocytosis via nicotinic receptors and
      inhibits melatonin synthesis in rat pinealocytes.
AB  - Rat pinealocytes, melatonin-secreting endocrine cells, contain peripheral
      glutaminergic systems. L-Glutamate is a negative regulator of melatonin synthesis
      through a metabotropic receptor-mediated inhibitory cAMP cascade. Previously, we
      reported that depolarization of pinealocytes by externally added KCl and
      activation of L-type Ca2+ channels resulted in secretion of L-glutamate by
      microvesicle exocytosis. What is unknown is how and what kinds of stimuli trigger
      glutamate exocytosis under physiological conditions. Here, we report that the
      nicotinic acetylcholine receptor can trigger glutamate exocytosis from cultured
      rat pinealocytes. Moreover, acetylcholine or nicotine inhibited norepinephrine
      dependent serotonin N-acetyltransferase activity, which results in decreased
      melatonin synthesis. These activities were blocked by (2S,3S, 4S)-2-methyl-2
      (carboxycyclopropyl)glycine, an antagonist of the metabotropic glutamate
      receptor. These results suggest that cholinergic stimulation initiates the
      glutaminergic signaling cascade in pineal glands and that parasympathetic neurons
      innervating the gland exert negative control over melatonin synthesis by way of
      the glutaminergic systems.

PMID- 9634561
TI  - Axon withdrawal during synapse elimination at the neuromuscular junction is
      accompanied by disassembly of the postsynaptic specialization and withdrawal of
      Schwann cell processes.
AB  - Nerve terminal withdrawal is accompanied by a loss of acetylcholine receptors
      (AChRs) at corresponding postsynaptic sites during the process of synapse
      elimination at developing () and reinnervated adult () neuromuscular junctions.
      Aside from AChR and nerve terminal loss, however, the molecular and cellular
      alterations that occur at sites of elimination are unknown. To gain a better
      understanding of the cascade of events that leads to the disassembly of synaptic
      sites during the synapse elimination process, we surveyed the distribution of
      molecular elements of the postsynaptic specialization, the basal lamina, and
      supporting Schwann cells during the process of synapse elimination that occurs
      after reinnervation. In addition, quantitative techniques were used to determine
      the temporal order of disappearance of molecules that were lost relative to the
      loss of postsynaptic AChRs. We found that the dismantling of the postsynaptic
      specialization was inhomogeneous, with evidence of rapid dissolution of some
      aspects of the postsynaptic apparatus and slower loss of others. We also observed
      a loss of Schwann cell processes from sites of synapse elimination, with a time
      course similar to that seen for nerve terminal retraction. In contrast, all of
      the extracellular markers that we examined were lost slowly from sites of synapse
      loss. We therefore conclude that the synapse elimination process is synapse-wide,
      removing not only nerve terminals but also Schwann cells and many aspects of the
      postsynaptic apparatus. The disassembly occurs in a stereotyped sequence with
      some synaptic elements appearing much more stable than others.

PMID- 9634562
TI  - Activity-dependent development of calcium regulation in growing motor axons.
AB  - In cultured nerve cord explants from the crayfish (Procambarus clarkii), the
      normal impulse activity levels of growing motor axons determine their response to
      Ca2+ influx. During depolarization or Ca2+ ionophore application, normally active
      tonic motor axons continue to grow, whereas inactive phasic motor axons retract
      and often degenerate. To determine the role of Ca2+ regulation in this
      difference, we measured the intracellular free Ca2+ concentration ([Ca2+]i) with
      fura-2. Growth cones from tonic axons normally had a higher [Ca2+]i than those
      from phasic axons. When depolarized with 60 mM K+, growth cones and neurites from
      phasic axons had a [Ca2+]i three to four times higher than did those from tonic
      axons. This difference in Ca2+ regulation includes greater Ca2+-handling capacity
      for growing tonic axons; the increase in [Ca2+]i produced by the Ca2+ ionophore 4
      bromo-A23187 (0.25 microM) is four to five times greater in phasic than in tonic
      axons, and the decline in [Ca2+]i at the end of a depolarizing pulse is three to
      four times faster in tonic axons than phasic ones. Blocking impulses in growing
      tonic axons for 2-3 d with tetrodotoxin reduces their capacity to regulate
      [Ca2+]i. Thus, growing tonic and phasic axons have differences in Ca2+ regulation
      that develop as a result of their different activity levels. These activity
      dependent differences in Ca2+ regulation influence axon growth and degeneration
      and probably influence other neuronal processes that are mediated by changes in
      [Ca2+]i.

PMID- 9634563
TI  - cAMP-mediated regulation of neurotrophin-induced collapse of nerve growth cones.
AB  - Neurotrophins are known to promote the survival, differentiation, and neurite
      outgrowth of developing neurons. Here we report that acutely applied brain
      derived neurotrophic factor (BDNF) induces rapid growth cone collapse and neurite
      retraction of embryonic Xenopus spinal neurons in culture. The collapsing effect
      of BDNF depends on the activation of Trk receptor tyrosine kinase, requires an
      influx of extracellular Ca2+, and is regulated by cAMP-dependent activity.
      Elevation of intracellular cAMP levels ([cAMP]i) by forskolin or (Sp)-cAMP
      completely blocked the collapsing effect, whereas inhibition of protein kinase A
      (PKA) by (Rp)-cAMP potentiated the collapsing action. BDNF-induced growth cone
      collapse was only observed in 6 hr cultures but not in 24 hr cultures. However,
      inhibition of PKA by (Rp)-cAMP restored the collapsing response of these "old"
      neurons in 24 hr cultures, suggesting that embryonic Xenopus spinal neurons may
      upregulate their endogenous cAMP-dependent activity during development in
      culture, leading to the blockade of their collapsing response to BDNF. Taken
      together, our results suggest the presence of cross-talk between Ca2+- and cAMP
      signaling pathways involved in the collapsing action of neurotrophins, in which
      the cAMP-pathway regulates the Ca2+-mediated signal transduction required for
      BDNF-induced collapse. By modulating the cAMP-dependent activity through the
      intrinsic programming or interaction with other factors present in the
      environment, a neuron thus could respond to the same extracellular factors with
      different morphological and cellular changes at different stages during
      development.

PMID- 9634564
TI  - Localized synaptic actions of neurotrophin-4.
AB  - Neurotrophins secreted by the postsynaptic target cell may participate in
      activity-dependent synaptic modification during development and in the mature
      brain. A fundamental question of how neurotrophins can sculpt synaptic
      connections is whether neurotrophin-induced synaptic changes are spatially
      restricted to the site of neurotrophin secretion or whether they can spread to
      neighboring synapses. Using a model system of nerve-muscle coculture in which
      neurotrophin-4 (NT-4) is overexpressed in a subpopulation of postsynaptic
      myocytes, we demonstrated that presynaptic potentiation is restricted to synapses
      on myocytes overexpressing NT-4 without affecting nearby synapses formed by the
      same neuron on control myocytes. Likewise, postsynaptic modulation of
      acetylcholine channels by secreted NT-4 is spatially restricted to <60 micron
      from the site of NT-4 secretion. Therefore, activity-dependent secretion of
      neurotrophins can result in highly localized modification of neuronal
      connections.

PMID- 9634565
TI  - GABAA receptor pharmacology and subtype mRNA expression in human neuronal NT2-N
      cells.
AB  - Human NT2 teratocarcinoma cells differentiate into neuron-like NT2-N cells when
      treated with retinoic acid. GABA evoked concentration-dependent whole-cell
      currents in NT2-N cells with an EC50 of 21.8 microM and a Hill slope of 1.2.
      GABAA receptor (GABAR) currents reversed at ECl- and did not display voltage
      dependent rectification. GABAR single channels opened in bursts to a 23 pS main
      conductance level and a 19 pS subconductance level, with infrequent openings to a
      27 pS conductance level. Kinetic properties of the main conductance level were
      similar to other native and recombinant GABAR channels. Diazepam and zolpidem
      enhanced GABAR currents with moderate affinity, whereas methyl-6, 7-dimethoxy-4
      ethyl-beta-carboline-3-carboxylate inhibited GABAR currents. Loreclezole enhanced
      GABAR currents with high affinity, but furosemide antagonized GABAR currents with
      low affinity. The neurosteroids alphaxalone and pregnenolone sulfate
      appropriately modulated GABAR currents. Zinc blocked GABAR currents with low
      affinity, but lanthanum did not significantly alter NT2-N GABAR currents. Reverse
      transcription PCR (RT-PCR) performed on RNA from NT2-N cells clearly detected
      transcripts encoding human alpha2, alpha3, alpha5, beta3, gamma3, and pi
      subtypes. The combined pharmacological and RT-PCR results are most consistent
      with a single or predominant GABAR isoform composed of an alpha2 and/or alpha3
      subtype combined with the beta3 and gamma3 subtypes. The data do not rule out
      receptors containing combinations of alpha2 and/or alpha3 subtypes with the
      alpha5 subtype or receptors with both beta1 and beta3 subtypes. The presence or
      absence or the pi subunit in functionally expressed receptors could not be
      determined.

PMID- 9634566
TI  - Differential withdrawal of retinal axons induced by a secreted factor.
AB  - To understand the development of the topographic map in the chick retinotectal
      projection, we studied the long-term interactions between retinal axons and
      tectal cell processes using a novel coculture system, the ryomen chamber. Both
      nasal and temporal retinal axons initially grew equally well on a substrate
      consisting of posterior tectal cell processes; however, subsequently most
      temporal axons withdrew from this surface, whereas most nasal axons did not.
      Experiments using conditioned media indicate that posterior tectal cells induced
      withdrawal of the temporal axons by secreting a soluble factor. This withdrawal
      seems to be distinct from the immediate repulsive effect of ephrin-A2 (ELF-1) and
      ephrin-A5 (RAGS) seen in the stripe assay because (1) the withdrawal-inducing
      factor was diffusible, whereas ephrin-A2 and -A5 are membrane-bound, and (2) the
      withdrawal-inducing factor appeared later in development than ephrin-A2 and -A5.
      Furthermore, sensitivity to the withdrawal-inducing factor decreased continuously
      from the temporal to nasal retina. These results suggest that target cell-induced
      axonal withdrawal may be involved during a late stage of the development of the
      retinotectal map.

PMID- 9634567
TI  - Blockade of glutamate-mediated activity in the developing retina perturbs the
      functional segregation of ON and OFF pathways.
AB  - The dendrites of ganglion cells initially ramify throughout the inner plexiform
      layer of the developing retina before becoming stratified into ON or OFF
      sublaminae. This ontogenetic event is thought to depend on glutamate-mediated
      afferent activity, because treating the developing retina with the glutamate
      analog 2-amino-4-phosphonobutyrate (APB), which hyperpolarizes ON cone bipolar
      cells and rod bipolar cells, thereby preventing their release of glutamate,
      effectively arrests the dendritic stratification process. To assess the
      functional consequences of this manipulation, extracellular recordings were made
      from single cells in the A laminae of the dorsal lateral geniculate nucleus and
      from the optic tract in mature cats that had received intraocular injections of
      APB during the first postnatal month. Such recordings revealed that stimulation
      of the APB-treated eye evoked both ON as well as OFF discharges in 37% of the
      cells tested. (As expected, when the normal eye was activated, virtually all
      cells yielded only ON or OFF responses.) The proportion of ON-OFF cells found
      here corresponds closely to the incidence of multistratified dendrites observed
      previously in anatomical studies of APB-treated cat retinas. This suggests that
      the ganglion cells with multistratified dendrites receive functional inputs from
      ON as well as OFF cone bipolar cells. This interpretation is further supported by
      the finding that the proportion of ON-OFF cells was very similar in the
      geniculate layer innervated by the treated eye and in the optic tract. The cells
      activated by the APB-treated eye were also found not to show response suppression
      when flashing stimuli of increasing size were used. This suggests that exposing
      the developing retina to APB perturbs the neural circuitry mediating the
      antagonistic center-surround organization found in normal receptive fields. The
      functional changes evident after treating the developing retina with APB suggest
      that it should now be feasible to assess how the segregation of ON and OFF
      retinal pathways relates to organizational features at higher levels of the
      visual system, such as orientation selectivity in cortical cells.

PMID- 9634568
TI  - The role of parietal cortex in verbal working memory.
AB  - Neuroimaging studies of normal subjects and studies of patients with focal
      lesions implicate regions of parietal cortex in verbal working memory (VWM), yet
      the precise role of parietal cortex in VWM remains unclear. Some evidence (; )
      suggests that the parietal cortex mediates the storage of verbal information, but
      these studies and most previous ones included encoding and retrieval processes as
      well as storage and rehearsal of verbal information. A recent positron emission
      tomography (PET) study by isolated storage and rehearsal from other VWM processes
      and did not find reliable activation in parietal cortex. This result suggests
      that parietal cortex may not be involved in VWM storage, contrary to previous
      proposals. However, we report two behavioral studies indicating that some of the
      verbal material used by may not have required phonological representations in
      VWM. In addition, we report a PET study that isolated VWM encoding, retrieval,
      and storage and rehearsal processes in different PET scans and used material
      likely to require phonological codes in VWM. After subtraction of appropriate
      controls, the encoding condition revealed no reliable activations; the retrieval
      condition revealed reliable activations in dorsolateral prefrontal, anterior
      cingulate, posterior parietal, and extrastriate cortices, and the storage
      condition revealed reliable activations in dorsolateral prefrontal, inferior
      frontal, premotor, and posterior parietal cortices, as well as cerebellum. These
      results suggest that parietal regions are part of a network of brain areas that
      mediate the short-term storage and retrieval of phonologically coded verbal
      material.

PMID- 9634569
TI  - Effects of pedunculopontine tegmental nucleus lesions on responding for
      intravenous heroin under different schedules of reinforcement.
AB  - The pedunculopontine tegmental nucleus (PPTg) is believed to play important roles
      in reward and learning. We examined the effect of PPTg lesions (0.5 microl of 0.1
      M NMDA injected bilaterally over 10 min) on the learning of an operant response
      for opiate reward. In 14 adult male Long-Evans rats, bilateral lesions of the
      PPTg disrupted the acquisition of responding for intravenous heroin (0.1 mg/kg
      infused at a rate of 0.25 ml/28 sec) on a fixed ratio-1 (FR-1) schedule of
      reinforcement. The 12 remaining lesioned animals increased their heroin intake
      over the acquisition sessions but did not reach the response levels of sham
      lesioned animals on the 15th and final session. The sham- and PPTg-lesioned
      animals that learned the FR-1 task exhibited similar patterns of responding
      during extinction and reacquisition sessions. When tested on a progressive ratio
      (PR) schedule of reinforcement, however, PPTg-lesioned animals had lower break
      points than sham-lesioned animals. Asymmetric lesions, which destroyed the
      majority of the nucleus in one hemisphere only, did not produce any behavioral
      deficits. Rats that were lesioned after training also did not show deficits in
      responding under either FR or PR schedules. These findings suggest that PPTg
      lesions reduce the rewarding effect of opiates but do not disrupt the ability
      either to learn an operant response or the response requirements of a PR
      schedule.

PMID- 9634570
TI  - Endogenous regulation of serotonin release in the hamster suprachiasmatic
      nucleus.
AB  - Serotonin (5-HT) has been strongly implicated in the regulation of the mammalian
      circadian clock located in the suprachiasmatic nuclei (SCN). However, little is
      known of the pattern of neuronal 5-HT release in the SCN or of the factors
      involved in regulating its release. Using in vivo microdialysis, we demonstrated
      the existence of a daily rhythm in the output of 5-HT in the SCN of freely
      behaving hamsters. This rhythm was characterized by a sharp increase in release
      from a nadir during late midday to peak levels at the light/dark transition.
      Output declined to basal levels throughout the remainder of the night. A similar
      pattern also was evident under constant darkness, with increased 5-HT output
      occurring at the onset of subjective night. Locomotor activity induced by
      exposure to a novel running wheel had a pronounced phase-dependent effect on 5-HT
      release in the SCN, with stimulation during the light phase and suppression
      during the late dark phase. Systemic application of the somatodendritic 5-HT1A
      agonist BMY 7378 had a significantly greater suppressive effect on 5-HT release
      in the SCN during the late dark phase compared with mid light phase, indicating
      that a variation in raphe autoreceptor response may underlie the time-dependent
      effects of wheel running on 5-HT release. Collectively, these results show that
      the daily rhythm in output of 5-HT in the SCN is generated endogenously, and that
      behavioral state can strongly influence serotonergic activity in the circadian
      clock in a phase-dependent manner.

PMID- 9634571
TI  - Frequency regulation of a slow rhythm by a fast periodic input.
AB  - Many nervous systems contain rhythmically active subnetworks that interact
      despite oscillating at widely different frequencies. The stomatogastric nervous
      system of the crab Cancer borealis produces a rapid pyloric rhythm and a
      considerably slower gastric mill rhythm. We construct and analyze a conductance
      based compartmental model to explore the activation of the gastric mill rhythm by
      the modulatory commissural neuron 1 (MCN1). This model demonstrates that the
      period of the MCN1-activated gastric mill rhythm, which was thought to be
      determined entirely by the interaction of neurons in the gastric mill network,
      can be strongly influenced by inhibitory synaptic input from the pacemaker neuron
      of the fast pyloric rhythm, the anterior burster (AB) neuron. Surprisingly, the
      change of the gastric mill period produced by the pyloric input to the gastric
      mill system can be many times larger than the period of the pyloric rhythm
      itself. This model illustrates several mechanisms by which a fast oscillatory
      neuron may control the frequency of a much slower oscillatory network. These
      findings suggest that it is possible to modify the slow rhythm either by direct
      modulation or indirectly by modulating the faster rhythm.

PMID- 9634572
TI  - Striatal extracellular dopamine levels in rats with haloperidol-induced
      depolarization block of substantia nigra dopamine neurons.
AB  - Correlations between substantia nigra (SN) dopamine (DA) cell activity and
      striatal extracellular DA were examined using simultaneous extracellular single
      unit recordings and in vivo microdialysis performed in drug-naive rats and in
      rats treated repeatedly with haloperidol (HAL). Intact rats treated with HAL for
      21-28 d exhibited significantly fewer active DA cells, indicating the presence of
      depolarization block (DB) in these cells. However, in rats that received surgical
      implantation of the microdialysis probe followed by a 24 hr recovery period, HAL
      induced DA cell DB was reversed, as evidenced by a number of active DA neurons
      that was significantly higher than that in HAL-treated intact rats and similar to
      that of drug-naive rats. In contrast, using a modified probe implantation
      procedure that did not reverse SN DA neuron DB, we found striatal DA efflux to be
      significantly lower than in controls and significantly correlated with the
      reduction in DA neuron spike activity. Furthermore, although basal striatal DA
      efflux was independent of SN DA cell burst-firing activity in control rats, these
      variables were significantly correlated in rats with HAL-induced DA cell DB.
      Therefore, HAL-induced DB of SN DA neurons is disrupted by implantation of a
      microdialysis probe into the striatum using standard procedures. However, a
      modified microdialysis method that allowed reinstatement of DA neuron DB revealed
      that the HAL-induced inactivation of SN DA neurons was associated with
      significantly lower extracellular DA levels in the striatum. Moreover, the
      residual extracellular DA maintained in the presence of DB may, in part, depend
      on the burst-firing pattern of the noninactivated DA neurons in the SN.

PMID- 9634573
TI  - Coadministration of galanin antagonist M40 with a muscarinic M1 agonist improves
      delayed nonmatching to position choice accuracy in rats with cholinergic lesions.
AB  - The neuropeptide galanin is overexpressed in the basal forebrain in Alzheimer's
      disease (AD). In rats, galanin inhibits evoked hippocampal acetylcholine release
      and impairs performance on several memory tasks, including delayed nonmatching to
      position (DNMTP). Galanin(1-13)-Pro2-(Ala-Leu)2-Ala-NH2 (M40), a peptidergic
      galanin receptor ligand, has been shown to block galanin-induced impairment on
      DNMTP in rats. M40 injected alone, however, does not improve DNMTP choice
      accuracy deficits in rats with selective cholinergic immunotoxic lesions of the
      basal forebrain. The present experiments used a strategy of combining M40 with an
      M1 cholinergic agonist in rats lesioned with the cholinergic immunotoxin 192IgG
      saporin. Coadministration of intraventricular M40 with intraperitoneal 3-(3-S-n
      pentyl-1,2,5-thiadiazol-4-yl)-1,2,5, 6-tetrahydro-1-methylpyridine (TZTP), an M1
      agonist, improved choice accuracy significantly more than a threshold dose of
      TZTP alone. These results suggest that a galanin antagonist may enhance the
      efficacy of cholinergic treatments for the cognitive deficits of AD.

PMID- 9634574
TI  - Small changes in ambient temperature cause large changes in 3,4
      methylenedioxymethamphetamine (MDMA)-induced serotonin neurotoxicity and core
      body temperature in the rat.
AB  - The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA) is a drug of
      abuse and has been shown to be neurotoxic to 5-HT terminals in many species. MDMA
      engendered neurotoxicity has been shown to be affected by both ambient
      temperature and core body temperature. We now report that small (2 degreesC)
      changes in ambient temperature produce changes in core temperature in MDMA
      treated rats, but the same changes in ambient temperature do not affect core
      temperature of saline-treated animals. Furthermore, increases in core temperature
      of MDMA-treated animals increase neurotoxicity. Rats were given MDMA (20 or 40
      mg/kg) or saline and placed in an ambient temperature of 20, 22, 24, 26, 28, or
      30 degreesC using a novel temperature measurement apparatus that controls ambient
      temperature +/-0.5 degrees C. Two weeks after MDMA treatment, the rats were
      killed, and regional 5-HT and 5-hydroxyindole acetic acid levels were analyzed as
      a measure of neurotoxicity. Rats treated with MDMA at 20 and 22 degrees C showed
      a hypothermic core temperature response. Treatment with MDMA at 28 and 30
      degreesC produced a hyperthermic response. At ambient temperatures of 20-24
      degrees C, neurotoxicity was not observed in the frontal cortex, somatosensory
      cortex, hippocampus, or striatum. At ambient temperatures of 26-30 degrees C,
      neurotoxicity was seen and correlated with core temperature in all regions
      examined. These data indicate that ambient temperature has a significant affect
      on MDMA neurotoxicity, core temperature, and thermoregulation in rats. This
      finding has implications on both the temperature dependence of the mechanism of
      MDMA neurotoxicity and human use because fatal hyperthermia is associated with
      MDMA use in humans.

PMID- 9634575
TI  - Electrophysiology of the hippocampal and amygdaloid projections to the nucleus
      accumbens of the rat: convergence, segregation, and interaction of inputs.
AB  - The nucleus accumbens (Nacb) receives inputs from hippocampus and amygdala but it
      is still unclear how these inputs are functionally organized and may interact.
      The interplay between these input pathways was examined using
      electrophysiological tools in the rat, in vivo, under halothane anesthesia. After
      fornix/fimbria stimulation (Fo/Fi, subicular projection fibers to the Nacb), mono
      and polysynaptically driven single units were recorded in the medial shell/core
      regions of the Nacb and in the ventromedial caudate putamen. Monosynaptically
      driven neurons by basolateral amygdala (BLA) stimulation were found in the medial
      shell/core and in the ventrolateral shell/core regions. In the areas of
      convergence (medial shell/core), paired activation of BLA followed by that of
      Fo/Fi resulted in an enhancement of the Fo/Fi response, whereas stimulation in
      the reverse order, Fo/Fi followed by BLA, led to a depression of the BLA
      response. In addition to these patterns of interactions, the tetanization of the
      Fo/Fi to Nacb pathway caused a homosynaptic decremental (long-term) potentiation
      in the Nacb, accompanied by a heterosynaptic (long-term) depression of the
      nontetanized BLA to Nacb pathway. We postulate that the hippocampal inputs may
      close a "gate" for the amygdala inputs, whereas the gate is opened for the
      hippocampus inputs by previous amygdalar activity. These opposite effects on the
      Nacb neuronal populations should be taken into account when interpreting
      behavioral phenomena, particularly with respect to the contrasting effects of the
      amygdala and the hippocampus in locomotion and place learning.

PMID- 9634576
TI  - Defense responses in plants and animals--more of the same.

PMID- 9634577
TI  - Transposon tagging of the Defective embryo and meristems gene of tomato.
AB  - The shoot and root apical meristems (SAMs and RAMs, respectively) of higher
      plants are mechanistically and structurally similar. This has led previously to
      the suggestion that the SAM and RAM represent modifications of a fundamentally
      homologous plan of organization. Despite recent interest in plant development,
      especially in the areas of meristem regulation, genes specifically required for
      the function of both the SAM and RAM have not yet been identified. Here, we
      report on a novel gene, Defective embryo and meristems (Dem), of tomato. This
      gene is required for the correct organization of shoot apical tissues of
      developing embryos, SAM development, and correct cell division patterns and
      meristem maintenance in roots. Dem was cloned using transposon tagging and shown
      to encode a novel protein of 72 kD with significant homology to YNV2, a protein
      of unknown function of Saccharomyces cerevisiae. Dem is expressed in root and
      shoot meristems and organ primordia but not in callus. The expression pattern of
      Dem mRNA in combination with the dem mutant phenotype suggests that Dem plays an
      important role within apical meristems.

PMID- 9634578
TI  - An Arabidopsis mutant hypersensitive to red and far-red light signals.
AB  - A new mutant called psi2 (for phytochrome signaling) was isolated by screening
      for elevated activity of a chlorophyll a/b binding protein-luciferase (CAB2-LUC)
      transgene in Arabidopsis. This mutant exhibited hypersensitive induction of CAB1,
      CAB2, and the small subunit of ribulose-1,5-bisphosphate carboxylase (RBCS)
      promoters in the very low fluence range of red light and a hypersensitive
      response in hypocotyl growth in continuous red light of higher fluences. In
      addition, at high- but not low-light fluence rates, the mutant showed light
      dependent superinduction of the pathogen-related protein gene PR-1a and developed
      spontaneous necrotic lesions in the absence of any pathogen. Expression of genes
      responding to various hormone and environmental stress pathways in the mutant was
      not significantly different from that of the wild type. Analysis of double
      mutants demonstrated that the effects of the psi2 mutation are dependent on both
      phytochromes phyA and phyB. The mutation is recessive and maps to the bottom of
      chromosome 5. Together, our results suggest that PSI2 specifically and negatively
      regulates both phyA and phyB phototransduction pathways. The induction of cell
      death by deregulated signaling pathways observed in psi2 is reminiscent of
      retinal degenerative diseases in animals and humans.

PMID- 9634579
TI  - Srchi13, a novel early nodulin from Sesbania rostrata, is related to acidic class
      III chitinases.
AB  - On the tropical legume Sesbania rostrata, stem-borne nodules develop after
      inoculation of adventitious root primordia with the microsymbiont Azorhizobium
      caulinodans. A cDNA clone, Srchi13, with homology to acidic class III chitinase
      genes, corresponds to an early nodulin gene with transiently induced expression
      during nodule ontogeny. Srchi13 transcripts accumulated strongly 2 days after
      inoculation, decreased from day 7 onward, and disappeared in mature nodules.
      Induction was dependent on Nod factor-producing bacteria. Srchi13 was expressed
      around infection pockets, in infection centra, around the developing nodule and
      its vascular bundles, and in uninfected cells of the central tissue. The specific
      and transient transcript accumulation together with the lipochitooligosaccharide
      degradation activity of the recombinant protein hint at a role of Srchi13 in
      normal nodule ontogeny by limiting the action of Nod factors.

PMID- 9634580
TI  - Inactivation of the sapA to sapF locus of Erwinia chrysanthemi reveals common
      features in plant and animal bacterial pathogenesis.
AB  - We investigated the role in pathogenesis of bacterial resistance to plant
      antimicrobial peptides. The sapA to sapF (for sensitive to antimicrobial
      peptides) operon from the pathogenic bacterium Erwinia chrysanthemi has been
      characterized. It has five open reading frames that are closely related (71%
      overall amino acid identity) and are in the same order as those of the sapA to
      sapF operon from Salmonella typhimurium. An E. chrysanthemi sap mutant strain was
      constructed by marker exchange. This mutant was more sensitive than was the wild
      type to wheat alpha-thionin and to snakin-1, which is the most abundant
      antimicrobial peptide from potato tubers. This mutant was also less virulent than
      was the wild-type strain in potato tubers: lesion area was 37% that of the
      control, and growth rate was two orders of magnitude lower. These results
      indicate that the interaction of antimicrobial peptides from the host with the
      sapA to sapF operon from the pathogen plays a similar role in animal and in plant
      bacterial pathogenesis.

PMID- 9634581
TI  - GOLDEN 2: a novel transcriptional regulator of cellular differentiation in the
      maize leaf.
AB  - The differentiation of distinct cell types within the leaf is essential for
      normal plant development. We characterized previously a transposon-induced mutant
      of maize (bundle sheath defective1) that disrupts the differentiation of a single
      photosynthetic cell type in the leaf. In this study, we show that this mutation
      is allelic to golden2 (g2), a lesion first reported 70 years ago. We cloned G2 by
      using Suppressor-mutator as a molecular tag. The gene encodes a 2. 2-kb
      transcript that is present throughout the wild-type leaf but is most abundant in
      C4 leaf blade tissue. Gene sequence data showed the existence of a bipartite
      nuclear localization signal encoded by the first exon, and we determined that G2
      reporter gene fusions are targeted to the nucleus in onion epidermal cells.
      Further sequence analysis indicated the presence of a novel motif within the
      deduced protein sequence that shares features with TEA DNA binding domains.
      Therefore, we propose that G2 acts as a novel transcriptional regulator of
      cellular differentiation in the maize leaf.

PMID- 9634582
TI  - Initiation and maintenance of virus-induced gene silencing 
AB  - The phytoene desaturase (PDS) gene of Nicotiana benthamiana was silenced in
      plants infected with potato virus X (PVX) vectors carrying PDS inserts, and a
      green fluorescent protein (GFP) transgene was silenced in plants infected with
      PVX-GFP. This virus-induced gene silencing (VIGS) is post-transcriptional and
      cytoplasmic because it is targeted against exons rather than introns of PDS RNA
      and against viral RNAs. Although PDS and GFP RNAs are most likely targeted
      through the same mechanism, the VIGS phenotypes differed in two respects. PDS
      mRNA was targeted by VIGS in all green tissue of the PVX-PDS-infected plant,
      whereas PVX-PDS was not affected. In contrast, VIGS of the GFP was targeted
      against PVX-GFP. Initially, VIGS of the GFP was initiated in all green tissues,
      as occurred with PDS VIGS. However, after 30 days of infection, the GFP VIGS was
      no longer initiated in newly emerging leaves, although it was maintained in
      tissue in which it had already been initiated. Based on these analyses, we
      propose a model for VIGS in which the initiation of VIGS is dependent on the
      virus and maintenance of it is virus independent.

PMID- 9634583
TI  - An Arabidopsis mutant with enhanced resistance to powdery mildew.
AB  - We have identified an Arabidopsis mutant that displays enhanced disease
      resistance to the fungus Erysiphe cichoracearum, causal agent of powdery mildew.
      The edr1 mutant does not constitutively express the pathogenesis-related genes PR
      1, BGL2, or PR-5 and thus differs from previously described disease-resistant
      mutants of Arabidopsis. E. cichoracearum conidia (asexual spores) germinated
      normally and formed extensive hyphae on edr1 plants, indicating that the initial
      stages of infection were not inhibited. Production of conidiophores on edr1
      plants, however, was <16% of that observed on wild-type Arabidopsis. Reduction in
      sporulation correlated with a more rapid induction of defense responses.
      Autofluorescent compounds and callose accumulated in edr1 leaves 3 days after
      inoculation with E. cichoracearum, and dead mesophyll cells accumulated in edr1
      leaves starting 5 days after inoculation. Macroscopic patches of dead cells
      appeared 6 days after inoculation. This resistance phenotype is similar to that
      conferred by "late-acting" powdery mildew resistance genes of wheat and barley.
      The edr1 mutation is recessive and maps to chromosome 1 between molecular markers
      ATEAT1 and NCC1. We speculate that the edr1 mutation derepresses multiple defense
      responses, making them more easily induced by virulent pathogens.

PMID- 9634584
TI  - Characterization of microtubule binding domains in the Arabidopsis kinesin-like
      calmodulin binding protein.
AB  - The kinesin-like calmodulin binding protein (KCBP) is a new member of the kinesin
      superfamily that appears to be present only in plants. The KCBP is unique in its
      ability to interact with calmodulin in a Ca2+-dependent manner. To study the
      interaction of the KCBP with microtubules, we expressed different regions of the
      Arabidopsis KCBP and used the purified proteins in cosedimentation assays with
      microtubules. The motor domain with or without the calmodulin binding domain
      bound to microtubules. The binding of the motor domain containing the calmodulin
      binding region to microtubules was inhibited by Ca2+-calmodulin. This Ca2+
      calmodulin regulation of motor domain interactions with microtubules was
      abolished in the presence of antibodies specific to the calmodulin binding
      region. In addition, the binding of the motor domain lacking the calmodulin
      binding region to microtubules was not inhibited in the presence of Ca2+
      calmodulin, suggesting an essential role for the calmodulin binding region in
      Ca2+-calmodulin modulation. Results of the cosedimentation assays with the N
      terminal tail suggest the presence of a second microtubule binding site on the
      KCBP. However, the interaction of the N-terminal tail region of the KCBP with
      microtubules was insensitive to ATP. These data on the interaction of the KCBP
      with microtubules provide new insights into the functioning of the KCBP in
      plants.

PMID- 9634585
TI  - A potential signaling role for profilin in pollen of Papaver rhoeas.
AB  - Regulation of pollen tube growth is known to involve alterations in intracellular
      calcium levels and phosphoinositide signaling, although the mechanisms involved
      are unclear. However, it appears likely that pollination events involve a complex
      interplay between signaling pathways and components of the actin cytoskeleton in
      pollen. In many eukaryotic cells, actin binding proteins function as stimulus
      response modulators, translating signals into alterations in the cytoplasmic
      architecture. In this study, we examined whether profilin, which is a member of
      this class of signaling intermediate, might play a similar role in pollen. We
      have analyzed the functional properties of native profilin from pollen of Papaver
      rhoeas and have investigated the effects of profilin on the phosphorylation of
      pollen proteins in vitro by adding a slight excess of profilin to cytosolic
      pollen extracts. We present clear evidence that profilin interacts with soluble
      pollen components, resulting in dramatic alterations in the phosphorylation of
      several proteins. We also show, albeit in vitro, the involvement of profilin in
      modulating the activity of a signaling component(s) affecting protein
      phosphorylation. Our data, which suggest that pollen profilin can regulate actin
      based cytoskeletal protein assembly and protein kinase or phosphatase activity,
      indicate a possible role for the involvement of profilin in signaling pathways
      that may regulate pollen tube growth.

PMID- 9634586
TI  - Pollen profilin function depends on interaction with proline-rich motifs.
AB  - The actin binding protein profilin has dramatic effects on actin polymerization
      in vitro and in living cells. Plants have large multigene families encoding
      profilins, and many cells or tissues can express multiple profilin isoforms.
      Recently, we characterized several profilin isoforms from maize pollen for their
      ability to alter cytoarchitecture when microinjected into living plant cells and
      for their association with poly-L-proline and monomeric actin from maize pollen.
      In this study, we characterize a new profilin isoform from maize, which has been
      designated ZmPRO4, that is expressed predominantly in endosperm but is also found
      at low levels in all tissues examined, including mature and germinated pollen.
      The affinity of ZmPRO4 for monomeric actin, which was measured by two independent
      methods, is similar to that of the three profilin isoforms previously identified
      in pollen. In contrast, the affinity of ZmPRO4 for poly-L-proline is nearly
      twofold higher than that of native pollen profilin and the other recombinant
      profilin isoforms. When ZmPRO4 was microinjected into plant cells, the effect on
      actin-dependent nuclear position was significantly more rapid than that of
      another pollen profilin isoform, ZmPRO1. A gain-of-function mutant (ZmPRO1-Y6F)
      was created and found to enhance poly-L-proline binding activity and to disrupt
      cytoarchitecture as effectively as ZmPRO4. In this study, we demonstrate that
      profilin isoforms expressed in a single cell can have different effects on actin
      in living cells and that the poly-L-proline binding function of profilin may have
      important consequences for the regulation of actin cytoskeletal dynamics in plant
      cells.

PMID- 9634587
TI  - Identification of a negative regulator of gibberellin action, HvSPY, in barley.
AB  - To broaden our understanding of the molecular mechanisms of gibberellin (GA)
      action, we isolated a spindly clone (HvSPY) from barley cultivar Himalaya and
      tested whether the HvSPY protein would modulate GA action in barley aleurone. The
      HvSPY cDNA showed high sequence identity to Arabidopsis SPY along its entire
      length, and the barley protein functionally complemented the spy-3 mutation.
      HvSPY and SPY proteins showed sequence relatedness with animal O-linked N
      acetylglucosamine transferases (OGTs), suggesting that they may also have OGT
      activity. HvSPY has a locus distinct from that of Sln, a mutation that causes the
      constitutive GA responses of slender barley, which phenotypically resembles
      Arabidopsis spy mutants. The possibility that the HvSPY gene encodes a negative
      regulator of GA action was tested by expressing HvSPY in a barley aleurone
      transient assay system. HvSPY coexpression largely abolished GA3-induced activity
      of an alpha-amylase promoter. Surprisingly, HvSPY coexpression increased reporter
      gene activity from an abscisic acid (ABA)-inducible gene promoter (dehydrin),
      even in the absence of exogenous ABA. These results show that HvSPY modulates the
      transcriptional activities of two hormonally regulated promoters: negatively for
      a GA-induced promoter and positively for an ABA-induced promoter.

PMID- 9634588
TI  - Two genes with similarity to bacterial response regulators are rapidly and
      specifically induced by cytokinin in Arabidopsis.
AB  - Cytokinins are central regulators of plant growth and development, but little is
      known about their mode of action. By using differential display, we identified a
      gene, IBC6 (for induced by cytokinin), from etiolated Arabidopsis seedlings, that
      is induced rapidly by cytokinin. The steady state level of IBC6 mRNA was elevated
      within 10 min by the exogenous application of cytokinin, and this induction did
      not require de novo protein synthesis. IBC6 was not induced by other plant
      hormones or by light. A second Arabidopsis gene with a sequence highly similar to
      IBC6 was identified. This IBC7 gene also was induced by cytokinin, although with
      somewhat slower kinetics and to a lesser extent. The pattern of expression of the
      two genes was similar, with higher expression in leaves, rachises, and flowers
      and lower transcript levels in roots and siliques. Sequence analysis revealed
      that IBC6 and IBC7 are similar to the receiver domain of bacterial two-component
      response regulators. This homology, coupled with previously published work on the
      CKI1 histidine kinase homolog, suggests that these proteins may play a role in
      early cytokinin signaling.

PMID- 9634589
TI  - PAD4 functions upstream from salicylic acid to control defense responses in
      Arabidopsis.
AB  - The Arabidopsis PAD4 gene was previously shown to be required for synthesis of
      camalexin in response to infection by the virulent bacterial pathogen Pseudomonas
      syringae pv maculicola ES4326 but not in response to challenge by the non-host
      fungal pathogen Cochliobolus carbonum. In this study, we show that pad4 mutants
      exhibit defects in defense responses, including camalexin synthesis and
      pathogenesis-related PR-1 gene expression, when infected by P. s. maculicola ES4
      326. No such defects were observed in response to infection by an isogenic
      avirulent strain carrying the avirulence gene avrRpt2. In P. s. maculicola ES4
      326-infected pad4 plants, synthesis of salicylic acid (SA) was found to be
      reduced and delayed when compared with SA synthesis in wild-type plants.
      Moreover, treatment of pad4 plants with SA partially reversed the camalexin
      deficiency and PR-1 gene expression phenotypes of P. s. maculicola ES4 326
      infected pad4 plants. These findings support the hypothesis that PAD4 acts
      upstream from SA accumulation in regulating defense response expression in plants
      infected with P. s. maculicola ES4 326. A working model of the role of PAD4 in
      governing expression of defense responses is presented.

PMID- 9634590
TI  - Sorting of phaseolin to the vacuole is saturable and requires a short C-terminal
      peptide.
AB  - Phaseolin, one of the major legume proteins for human nutrition, is a trimeric
      glycoprotein of the 7S class that accumulates in the protein storage vacuoles of
      common bean. Phaseolin is cotranslationally introduced into the lumen of the
      endoplasmic reticulum; from there, it is transported through the Golgi complex to
      the storage vacuoles. Phaseolin is also transported to the vacuole in vegetative
      tissues of transgenic plants. By transient and permanent expression in tobacco
      leaf cells, we show here that vacuolar sorting of phaseolin is saturable and that
      saturation leads to Golgi-mediated secretion from the cell. A mutated phaseolin,
      in which the four C-terminal residues (Ala, Phe, Val, and Tyr) were deleted,
      efficiently formed trimers but was secreted entirely outside of the cells in
      transgenic tobacco leaves, indicating that the deleted sequence contains
      information necessary for interactions with the saturable vacuolar sorting
      machinery. In the apoplast, the secreted phaseolin remained intact; this is
      similar to what occurs to wild-type phaseolin in bean storage vacuoles, whereas
      in vegetative vacuoles of transgenic plants, the storage protein is fragmented.

PMID- 9634591
TI  - The Arabidopsis abscisic acid response locus ABI4 encodes an APETALA 2 domain
      protein.
AB  - Arabidopsis abscisic acid (ABA)-insensitive abi4 mutants have pleiotropic defects
      in seed development, including decreased sensitivity to ABA inhibition of
      germination and altered seed-specific gene expression. This phenotype is
      consistent with a role for ABI4 in regulating seed responses to ABA and/or seed
      specific signals. We isolated the ABI4 gene by positional cloning and confirmed
      its identity by complementation analysis. The predicted protein product shows
      homology to a plant-specific family of transcriptional regulators characterized
      by a conserved DNA binding domain, the APETALA 2 domain. The single mutant allele
      identified has a single base pair deletion, resulting in a frameshift that should
      disrupt the C-terminal half of the protein but leave the presumed DNA binding
      domain intact. Expression analyses showed that despite the seed-specific nature
      of the mutant phenotype, ABI4 expression is not seed specific.

PMID- 9634592
TI  - Dissection of the fusarium I2 gene cluster in tomato reveals six homologs and one
      active gene copy.
AB  - The I2 locus in tomato confers resistance to race 2 of the soil-borne fungus
      Fusarium oxysporum f sp lycopersici. The selective restriction fragment
      amplification (AFLP) positional cloning strategy was used to identify I2 in the
      tomato genome. A yeast artificial chromosome (YAC) clone covering approximately
      750 kb encompassing the I2 locus was isolated, and the AFLP technique was used to
      derive tightly linked AFLP markers from this YAC clone. Genetic complementation
      analysis in transgenic R1 plants using a set of overlapping cosmids covering the
      I2 locus revealed three cosmids giving full resistance to F. o. lycopersici race
      2. These cosmids shared a 7-kb DNA fragment containing an open reading frame
      encoding a protein with similarity to the nucleotide binding site leucine-rich
      repeat family of resistance genes. At the I2 locus, we identified six additional
      homologs that included the recently identified I2C-1 and I2C-2 genes. However,
      cosmids containing the I2C-1 or I2C-2 gene could not confer resistance to plants,
      indicating that these members are not the functional resistance genes. Alignments
      between the various members of the I2 gene family revealed two significant
      variable regions within the leucine-rich repeat region. They consisted of
      deletions or duplications of one or more leucine-rich repeats. We propose that
      one or both of these leucine-rich repeats are involved in Fusarium wilt
      resistance with I2 specificity.

PMID- 9634593
TI  - A role for vesicles in human basophil secretion.
AB  - The evidence for vesicular transport as a mechanism for secretion by human
      basophils is reviewed. Initially, direct electron-microscopic inspection of
      experimentally produced and sequentially biopsied contact allergy skin lesions
      revealed a unique form of secretion termed piecemeal degranulation, characterized
      by the slow emptying of secretory granule contents (with retention of empty
      containers) in the absence of extrusion of entire granules. Budding of small
      vesicles to/from secretory granules was observed, and cytoplasmic vesicles were
      abundant. A generalized degranulation model was proposed to unify classical
      regulated secretion and this new form of secretion. Investigation of the
      mechanism(s) of secretion from human basophils required the development of
      numerous tools and resources. Chief among these were: (a) isolation and
      purification of circulating basophils; (b) identification of specific growth
      factors to increase the supply of this rare granulocyte; (c) understanding of
      secretogogue mechanisms and reliable analyses of secreted basophil products; and
      (d) development of ultrastructural preparations allowing imaging of small
      vesicles and quantifiable small electron-dense tags for granule materials in
      small vesicles. Applications of these tools to well-defined models of basophil
      secretion have established a role for vesicles as a mechanism for effecting
      secretion of histamine and the Charcot-Leyden crystal protein from activated
      human basophils.

PMID- 9634595
TI  - Cellular localization of neuropeptide Y mRNA and peptide in the brain of the
      Japanese quail and domestic chicken.
AB  - Neuropeptide Y (NPY) has been implicated in the control of a number of
      physiological functions in birds including food intake and reproduction. In the
      present study, sites of NPY synthesis were localized in the brains of Japanese
      quail and domestic chickens by in situ hybridization histochemistry using a
      digoxigenin-labelled riboprobe. NPY mRNA was detected in three main cell groups
      in both species. The most prominent group was associated with structures in the
      lateral thalamus including the anterior lateral thalamic nucleus, lateral
      forebrain bundle, rotund nucleus, pretectal nucleus and occipitomesencephalic
      tract. Other major cell groups were detected in the hippocampus, and in the
      caudal linear nucleus and raphe nucleus of the brainstem. NPY mRNA was also
      present in the piriform cortex and taenial nucleus. Double-labelling of NPY mRNA
      and peptide was demonstrated in individual cells of the hippocampal, thalamic and
      brainstem cell groups, suggesting that NPY is synthesized and stored in these
      areas. However, the identity of other cell groups, notably in the hyperstriatal,
      archistriatal and neostriatal regions of the telencephalon, which exhibit NPY
      immunoreactive cell bodies but no NPY mRNA, remains to be determined.

PMID- 9634594
TI  - Regulated expression of neurogenic basic helix-loop-helix transcription factors
      during differentiation of the immortalized neuronal progenitor cell line HC2S2
      into neurons.
AB  - Expression of nine neurogenic basic helix-loop-helix (bHLH) transcription factors
      was examined in an immortalized neuronal progenitor cell line HC2S2, which
      differentiates into neurons after suppression of the v-myc expression with
      tetracycline. Expression of MASH-1, NeuroD, NeuroD-related factor (NDRF) and HES
      1 was demonstrated in HC2S2 cells by Northern blot analysis using total RNA.
      Expression of MASH-1 mRNA was downregulated upon differentiation of HC2S2 cells
      into mature neurons. In contrast, NeuroD and NDRF mRNA expression was maintained
      all through the differentiation. The expression of HES-1, a negative regulator of
      the neuronal differentiation, was upregulated temporarily in accordance with the
      suppression of the v-myc expression and was downregulated upon the
      differentiation of HC2S2 cells into neurons. The reduced expression of HES-1 mRNA
      in undifferentiated HC2S2 cells may be explained by the transcriptional
      suppression of HES-1 by the myc oncoprotein. The above data imply that both HES-1
      and MASH-1 need to be downregulated at the time of accomplishment of the terminal
      differentiation into mature neurons and that NeuroD and NDRF participate in the
      regulatory process of the terminal differentiation in combination.

PMID- 9634596
TI  - Confocal laser scanning and electron-microscopic analyses of the relationship
      between VIP-like and GnRH-like-immunoreactive neurons in the lateral septal
      preoptic area of the pigeon.
AB  - The lateral septum and the preoptic area of birds comprise neurons immunoreactive
      (ir) for vasoactive intestinal polypeptide (VIP) and gonadotropin-releasing
      hormone (GnRH). By use of immunohistochemical single- and double-labeling
      techniques, we have investigated the distribution and the connections of these
      two types of peptidergic neurons in the lateral septal-preoptic area of the
      pigeon at both the light- and electron-microscopic levels. An accumulation of VIP
      like-ir neurons, some of which are cerebrospinal fluid-contacting neurons, is
      found in the area adjacent to the ventromedial walls of the lateral ventricles in
      the lateral septum corresponding to the medial part of the lateral septal organ.
      VIP-like-ir terminals are scattered throughout the lateral septal-preoptic area,
      which also contains GnRH-like-ir cell bodies. The number of GnRH-like-ir cell
      bodies in the lateral septum is smaller than that of the VIP-like-ir neurons.
      GnRH-like-ir cells have a simple bipolar or multipolar shape and a beaded axon
      that emerges from the soma or one of the proximal dendrites. Confocal laser
      scanning microscopy has shown VIP-like-ir terminals in close apposition to GnRH
      like-ir cell bodies in the lateral septal-preoptic area. Furthermore, the
      electron-microscopic double-immunolabeling has revealed synaptic contacts between
      VIP-like-ir axon terminals and GnRH-like-ir cell bodies or dendrites. These
      contacts, however, do not show synaptic specializations. The present results
      suggest that functional interactions take place between VIP and GnRH neurons in
      the lateral septal-preoptic area of the pigeon and that these interactions are
      involved in mediating photoperiodic responses.

PMID- 9634597
TI  - Organization of atrial natriuretic factor-like immunoreactive system in the brain
      of the frog Rana esculenta during development.
AB  - Immunocytochemical distribution of the atrial natriuretic factor (ANF) has been
      studied in the brain and pituitary of the anuran Rana esculenta during
      development and in juvenile animals. Using human ANF and rat alpha-ANF antisera,
      immunoreactive cell bodies and nerve fibers were revealed in stage II-III
      tadpoles and in successive larval stages. Soon after hatching, stages II-III, the
      ANF-like-immunoreactive elements were confined to the preoptic area-median
      eminence complex. During successive stages of development, new groups of ANF
      immunoreactive cell bodies appeared. In larval stage VI, immunoreactive perikarya
      were found in the rostral part of the anteroventral area of the thalamus and
      numerous ANF-like-immunoreactive cells appeared in the pars distalis of the
      pituitary. In larval stages XIV and XVIII, the distribution of ANF
      immunoreactivity was virtually similar. The ANF-immunoreactive cells in the
      preoptic nucleus and in the pituitary pars distalis were comparatively more
      abundant than in stage VI. During the metamorphic climax (stages XXI-XXII), a new
      group of ANF-immunoreactive cell bodies appeared in the rostral part of the
      ventrolateral area of the thalamus. During this stage, ANF-immunoreactive fiber
      projections were found in the pars intermedia for the first time. However, the
      pars distalis cells were very weakly immunofluorescent. The pattern of ANF
      immunoreactivity in the brain of juvenile animals was very similar to that
      described for stages XXI and XXII, whereas the pars distalis cells showed no
      immunoreactivity. It is conceivable that, early during development, ANF-related
      peptides may be involved in the regulation of pituitary secretion by means of
      autocrine mechanisms or may act as a classic pituitary hormone.

PMID- 9634598
TI  - Adenylyl cyclase co-distribution with the CaBPs, calbindin-D28 and calretinin,
      varies with cell type: assessment with the fluorescent dye, BODIPY forskolin, in
      enteric ganglia.
AB  - The aims of the present study were: (1) to evaluate BODIPY forskolin as a
      suitable fluorescent marker for membrane adenylyl cyclase (AC) in living enteric
      neurons of the guinea-pig ileum; (2) to test the hypothesis that AC is
      distributed in several subpopulations of enteric neurons; (3) to test the
      hypothesis that the distribution of AC in the myenteric plexus is not unique to
      AH/Type 2 neurons. BODIPY forskolin was used to assess the co-distribution of AC
      in ganglion cells expressing the specific calcium-binding proteins (CaBPs),
      calretinin, calbindin-D28, and s-100. Cultured cells or tissues were incubated
      with 10 microM BODIPY forskolin for 30 min and fluorescent labeling was monitored
      by using laser scanning confocal microscopy. BODIPY forskolin stained the cell
      soma, neurites, and nerve varicosities of Dogiel Type I or II neurons. About 99%
      of myenteric and 27% of submucous ganglia contained labeled neurons. About 14% of
      myenteric and 3% of submucous glia with immunoreactivity for s-100 protein
      displayed BODIPY forskolin fluorescence. BODIPY forskolin differentially labeled
      myenteric neurons immunoreactive for calbindin-D28 (80%) and calretinin (17%).
      The majority (63%) of BODIPY forskolin-labeled myenteric neurons displayed no
      immunoreactivity for either CaBP. In submucous ganglia, the dye labeled 44.6% of
      calretinin-immunoreactive neurons, representing 21% of all labeled neurons; it
      also labeled varicose nerve fibers running along blood vessels. AC thus exists in
      myenteric Dogiel type II/AH neurons, enteric cholinergic S/Type 1 neurons, and
      other unidentified non-cholinergic S/Type 1 neurons. Our data also support the
      hypothesis that AC is expressed in distinct functional subpopulations of AH and S
      neurons in enteric ganglia, and show that BODIPY forskolin is a suitable marker
      for AC in immunofluorescence co-distribution studies involving living cells or
      tissues.

PMID- 9634599
TI  - Plasticity of Congo red staining displayed by subpopulations of neurons within
      the rat central nervous system.
AB  - We document the presence of subpopulations of neurons within the rat central
      nervous system that are labelled with a new Congo red staining technique. These
      neurons (CR neurons) show shrunken somata, and smaller and darker nuclei than
      Congo red-negative cells (non-CR cells). With the Bielschowsky and the cresyl
      violet Nissl staining methods, two comparable subpopulations of cells can be
      distinguished by the same morphometrical criteria as those used for CR and non-CR
      cells. CR neurons are located preferentially in some brain regions while in
      others they are virtually absent. Their distribution and proportion varied
      greatly from animal to animal and after particular treatments. Injections of
      water that damaged the hippocampal dentate gyrus, cortical lesions or eye
      enucleation decreased the number of CR-cells in the CA1 subfield, reflected in a
      shift from the CR-staining subclass to the non-CR subclass. Treatment with 200
      mg/kg of CDP-choline also significantly reduced the number of CR cells observed
      in CA1. In the red nucleus, CR neurons showed a characteristic distribution of
      beta-amyloid precursor protein (APP) immunoreactivity. The population of
      dendrites immunolabelled for microtubule-associated protein 2 was markedly
      decreased in the areas of the hippocampus with high numbers of CR cells.
      Therefore, it is proposed that neurons labelled with the present Congo red
      technique might be in a reversible degenerative state or represent a particular
      physiological state in some areas of the central nervous system.

PMID- 9634600
TI  - Light- and electron-microscopic study of the distribution of axons containing
      substance P and the localization of neurokinin-1 receptor in bone.
AB  - Substance P (SP) is a neuropeptide that is released from axons of sensory neurons
      and causes signal transduction through the activation of the neurokinin-1
      receptor (NK1-R). The present study demonstrates the distribution of SP-like
      immunoreactive (SP-LI) axons and the localization of NK1-Rs in rat bone tissue
      using the avidin-biotin-peroxidase complex method. Axons with SP-LI were commonly
      found near the trabecular bone in the temporal bone marrow, but they were only
      sparsely distributed in the mandible, femur, and tibia. Immunoreactivity for NK1
      Rs was found on the plasma membrane and in the cytoplasm of the osteoclasts. In
      the osteoblasts and osteocytes, a small number of weak, punctate immunoreactive
      products of NK1-Rs were distributed close to the plasma membrane. At the electron
      microscopic level, immunoreactivity for NK1-R was distributed mainly in the whole
      cytoplasm, except for the clear zone of the osteoclasts, and in pit-like
      structures along the plasma membrane. The NK1-R-immunoreactive structures in the
      cytoplasm were divided into two types of organelles, consisting of vesicular and
      vacuolar structures (probably transport vesicles and early endosomes). In the
      osteoblasts and osteocytes, the number of NK1-R-positive vesicular structures was
      fewer than in the osteoclasts. These results thus suggest that SP secreted by the
      sensory axons could directly modulate bone metabolism via NK1-Rs.

PMID- 9634601
TI  - Expression pattern for adrenomedullin during pancreatic development in the rat
      reveals a common precursor with other endocrine cell types.
AB  - Adrenomedullin is an alpha-amidated 52-amino acid peptide involved in many
      physiological actions, among others the regulation of insulin secretion. Using
      immunohistochemical methods, we found that adrenomedullin immunoreactivity first
      appears at day 11.5 of embryonic development in the rat, coinciding with the
      appearance of pancreatic glucagon. The early appearance of adrenomedullin in the
      developing pancreas may indicate an active involvement in either the
      morphogenesis of the organ or its endocrine/paracrine/autocrine hormone
      regulation during intrauterine life. We also investigated the pattern of
      colocalizations of adrenomedullin with the other pancreatic hormones. At some
      point during development all the cell types express adrenomedullin, progressively
      evolving towards the adult pattern where only the pancreatic polypeptide cells
      contain a strong immunoreactivity for adrenomedullin. At this point the remaining
      cells of the islet are, in general, weakly stained. This sequential and time
      dependent expression of adrenomedullin suggests a tight regulation similar to
      that observed for other modulatory substances responsible for embryonic
      morphogenesis.

PMID- 9634602
TI  - Protein and fatty acid composition of caveolae from apical plasmalemma of aortic
      endothelial cells.
AB  - In endothelial cells (EC), caveolae or plasmalemmal vesicles (PVs) represent a
      structurally and biochemically specialized membrane microdomain. Since few data
      are available on the biochemical composition of PVs of large vessel endothelium,
      we have designed experiments to isolate this domain and to analyze its chemical
      components. A highly purified apical membrane fraction was obtained from cultured
      bovine aortic EC by using cationic colloidal silica (silica-ap), or the EC were
      surface-radioiodinated and a cell homogenate was prepared. Detergent treatment
      (Triton X-100; TX) and mechanical disruption of both the silica-ap fraction and
      cell homogenate followed by ultracentrifugation on a sucrose gradient gave
      detergent-soluble and detergent-insoluble membranous fractions. The lowest
      density TX-insoluble fraction appeared morphologically as distinct vesicles
      (caveolae; 60 nm average diameter; PVs fraction). Biochemical characterization of
      the PVs fraction (by comparison with the soluble fraction) revealed the presence,
      at high concentration, of specific caveolar markers, viz., caveolin (both
      isoforms, the 24-kDa form being conspicuously more abundant) and Ca2+-ATPase. By
      contrast, angiotensin-converting enzyme and alkaline phosphodiesterase were
      present almost exclusively in the TX-soluble fraction. The glycoproteins in the
      PVs fraction were of apparent molecular weights 52, 68, 95, and 114 kDa. Analysis
      of the fatty acid composition revealed more palmitoleic and stearic acid in the
      PVs fraction then in the TX-soluble fraction. Thus, in comparison with the
      plasmalemma proper, the PVs fraction (1) is detergent-insoluble; (2) contains
      caveolin in two isoforms; (3) contains Ca2+-ATPase at high concentration; (4)
      contains a set of specific glycoproteins; and (5) is enriched in palmitoleic and
      stearic acids.

PMID- 9634603
TI  - Bovine mast cells: distribution, density, heterogeneity, and influence of
      fixation techniques.
AB  - Mast cells can be distinguished according to various characteristics: rodent mast
      cells have been subtyped by histochemical criteria, whereas canine and human mast
      cells have been classified according to their proteases. Comparisons of mast
      cells from different species have therefore resulted in contradictory and
      confusing opinions on mast cell heterogeneity. Thus, it is essential to obtain
      species-specific data on mast cell density and heterogeneity. The present study
      was carried out to determine the physiological distribution of mast cell numbers
      and types in bovines according to tissue location, staining, and fixation
      methods. Samples were fixed in formalin or Carnoy's fluid. The average number of
      mast cells was determined by using a metachromatic staining method. Protease
      content of mast cells was examined with a double-enzyme-immunohistochemical
      staining technique. Three mast cell subtypes were distinguished: T-, TC-, and C
      mast cells. The T-mast cell was the predominant subtype in nearly all
      investigated organs and tissue locations. Only tryptase-positive mast cells could
      be demonstrated in bovine skin and uterus. No chymase activity was found in these
      organs, regardless of the fixation type. A larger number of mast cells was
      observed after fixation in Carnoy's fluid. The three different mast cell subtypes
      were only demonstrated in formalin-fixed tissue; chymase-positive mast cells were
      not found after fixation in Carnoy's fluid. Increasing experimental data suggest
      that mast cell subtypes have different functions in promoting and modulating
      inflammation and in remodeling the extracellular matrix. Since mast cell tryptase
      and chymase have different functional properties, these results may clarify the
      different reaction patterns observed in various organs and species.

PMID- 9634604
TI  - Immunocytochemistry and in situ hybridization studies of pepsinogen C-producing
      cells in developing rat fundic glands.
AB  - The ontogeny of pepsinogen C-producing cells in rat fundic glands was studied by
      means of light and electron microscopy using an antiserum raised against a
      synthetic peptide based on rat pepsinogen C. To confirm the immunocytochemistry
      results, the expression of rat pepsinogen C messenger RNA (mRNA) in the fundic
      gland was also examined by in situ hybridization using a digoxigenin-labeled RNA
      probe. In adult rats, pepsinogen C was produced by chief cells, mucous neck
      cells, and intermediate mucopeptic cells. Pepsinogen C-producing cells appeared
      in embryos as early as 18.5 days' gestation. The development of these cells could
      be classified into four stages: (1) 18.5 days' gestation to 0.5 days after birth;
      (2) 0.5 days to 2 weeks after birth; (3) 3-4 weeks after birth; (4) 4-8 weeks
      after birth. In embryos and young animals, pepsinogen C-producing cells were
      mucopeptic cells. By 4 weeks after birth, mucous neck cells could be
      distinguished morphologically. The maturation stages of the chief cells could be
      traced by electron microscopy along the longitudinal axis of the rat fundic gland
      by double-staining with anti-pepsinogen C antibody and periodic acid
      thiocarbohydrazide-silver proteinate. Positive reactions for pepsinogen C and
      pepsinogen C mRNA expression were detected in mucous neck cells. Therefore, we
      conclude that mucous neck cells are precursor cells of chief cells. Mucous neck
      cells, intermediate cells, and chief cells are in the same differentiating cell
      lineage.

PMID- 9634605
TI  - Methodological aspects of assessing phagocytosis of Vibrio anguillarum by
      leucocytes of gilthead seabream (Sparus aurata L.) by flow cytometry and electron
      microscopy.
AB  - In this paper we optimize a flow cytometric method for evaluating the phagocytic
      activity of leucocytes in gilthead seabream (Sparus aurata L.) and characterize
      the phagocytic cells observed. Optimal conditions were established for the
      fluorescein-labelling and analysis of the bacterium Vibrio anguillarum by flow
      cytometry. Head-kidney leucocytes were incubated with the heat-killed fluorescein
      isothiocyanate (FITC)-labelled bacteria for different periods, during which the
      kinetics of phagocytosis was studied. Attached and interiorized bacteria were
      distinguished. Although phagocytic ability reached a maximum after 60 min,
      phagocytic capacity reached its maximum at 20 min. The amount of ingested
      bacteria per phagocyte was estimated from the mean fluorescence of the
      leucocytes. Cytochalasin B or colchicine was used to inhibit phagocytosis.
      Monocyte-macrophages and acidophilic granulocytes showed phagocytic activity as
      demonstrated by transmission electron microscopy. In conclusion, the technique
      presented allows the screening of thousands of cells, and individual cell
      evaluation, by quantifying interiorized particles in fish phagocytes. Our
      ultrastructural results demonstrate that V. anguillarum is actively phagocytized
      by seabream macrophages and acidophilic granulocytes.

PMID- 9634606
TI  - Special smooth muscle cells along the submucosal surface of the guinea pig colon
      with reference to its spontaneous contractions.
AB  - Antiperistalses occur from the flexure region of the guinea pig colon. We
      previously demonstrated that the circular muscle at the mesenteric border of the
      flexure region produced spontaneous regular contractions and found special smooth
      muscle cells believed to be pacemakers along the submucosal surface of the
      circular muscle layer. In this study, we revealed bipolar- and multipolar-type
      special smooth muscle cells along the submucosal surface of the muscle layer.
      Their slender cell processes contacted each other and formed a cellular network.
      Caveolae, filament structures expressing smooth muscle actin, vimentin, some
      desmin, and basal lamina were prominent features. The special smooth muscle cells
      corresponded to c-Kit-immunopositive cells and so-called interstitial cells or
      interstitial cells of Cajal in other reports. Their population was larger in the
      flexure region and the proximal colon than in the distal colon. The circular
      muscle layer at the flexure region was thicker than in other regions. The
      contraction in the flexure region showed the highest frequency and regularity.
      The dense population of special smooth muscle cells at the flexure region and
      thicker muscle layer may make the mechanical contraction more regular. The
      antiperistalsis from the flexure region could be explained in relation to the
      highest frequency of the pulsating contraction.

PMID- 9634607
TI  - Corpuscles of Stannius and stanniocalcin-like immunoreactivity in the white
      sucker (Catostomus commersoni): evidence for a new cell-type.
AB  - The distribution of stanniocalcin immunoreactivity was examined in the corpuscles
      of Stannius of the white sucker (Catostomus commersoni) by using a chum salmon
      stanniocalcin antiserum, Western blotting, and light and electron microscopy. The
      white sucker possesses at least two stanniocalcin-immunoreactive corpuscles in
      the most posterior portions of the kidneys. Immunocytochemistry and
      ultrastructure revealed two cell-types in the corpuscle parenchyma, only one of
      which was immunoreactive. The nonimmunoreactive cells contained dense-cored
      vesicles and long processes that extended between the immunoreactive cells and
      terminated at perivascular spaces. When corpuscle extracts were subjected to
      electrophoresis and Western blotting, three nonreduced stanniocalcin-like
      immunoreactive bands (approximately 56, 61, and 64 kDa) were observed. However,
      in the presence of a reductant, a diffuse band migrating in the range of 28 to 32
      kDa was noted. The results of this study on the white sucker demonstrate the
      presence of a dimeric stanniocalcin-like molecule and present evidence of a
      previously uncharacterized cell-type in the corpuscles of Stannius.

PMID- 9634608
TI  - Segmental muscle fiber lesions after repetitive eccentric contractions.
AB  - Immunohistochemical and electron-microscopic techniques were used to analyze the
      extensor digitorum longus muscles of New Zealand White rabbits 1 h, 1 day, 3, 7,
      and 28 days after repetitive eccentric contractions. Loss of the cytoskeletal
      protein desmin was the earliest manifestation of injury. Apart from 1 h post
      exercise, all desmin-negative fibers stained positively with antibody to plasma
      fibronectin, indicating loss of cellular integrity accompanying cytoskeletal
      disruption. Fiber sizes were significantly increased from 1-7 days after
      exercise. The large (hyaline) fibers found in histological sections after
      repetitive eccentric contractions resulted from segmental hypercontraction of the
      fiber. This phenomenon occurred proximally and distally to plasma membrane
      lesions of the muscle fiber and necrosis and manifested itself as very short
      sarcomere lengths. Thus, in serial sections, staining characteristics, sizes and
      shapes of one and the same fiber often varied dramatically. We conclude that the
      following sequence of events occurs: cytoskeletal disruptions, loss of
      myofibrillar registry, i.e., Z-disk streaming and A-band disorganization, and
      loss of cell integrity as manifested by intracellular plasma fibronectin stain,
      hypercontracted regions, and invasion of cells. When a fiber is disrupted, the
      remaining intact fibers apparently take up the tension put on the muscle and
      later fewer fibers are subjected to eccentric contractions.

PMID- 9634609
TI  - Ultrastructural and lanthanum tracer examination of rapidly resorbing rat
      alveolar bone suggests that osteoclasts internalize dying bone cells.
AB  - Glutaraldehyde-formaldehyde fixed undecalcified alveolar bone from 7-day-old rats
      was prepared for light and electron microscopy. Colloidal lanthanum was used as
      an ultrastructural tracer, and both random and semi-serial sections were
      examined. Lanthanum penetrated the infoldings of the ruffled border and some
      nearby vacuoles and vesicles. The majority of vacuoles and vesicles were
      lanthanum-free. Some osteoclast profiles contained a large vacuole with a cell
      enclosed in its interior. The enclosed cell exhibited an irregular nucleus
      containing condensed peripheral chromatin, intact cytoplasmic organelles,
      conspicuous rough endoplasmic reticulum and large blebs on the cell surface.
      These features are characteristic of osteoblasts or bone-lining cells or immature
      osteocytes which may be undergoing apoptosis or necrosis. The observation of
      remnants of cellular structures within internalized osteoclast vacuoles, together
      with the above results, suggests that osteoclasts engulf and probably degrade
      dying osteoblasts/bone-lining cells or immature osteocytes.

PMID- 9634638
TI  - Mechanisms regulating the binding activity of CD44 to hyaluronic acid.
AB  - CD44 is a cell surface glycoprotein present on many cell types. Many CD44
      isoforms have been identified. All CD44 isoforms utilize identical transmembrane
      and cytoplasmic domains. The hematopoietic form of CD44 (CD44H) is the major CD44
      protein present on normal human lymphocytes and monocytes. One of the ligands for
      CD44 is hyaluronic acid (HA), a polymer consisting of repeat units of
      disaccharide; N-acetyl-D-glucosamine and N-acetyl-D-glucuronic acid. Since HA is
      present ubiquitously in extracellular matrix and in circulation, promiscuous
      binding of HA to CD44 may have undesirable affect. Similar to other adhesion
      molecules, binding of HA to cell surface CD44 requires regulation. In this
      review, we summarized our studies using a human lymphoma cell line, Jurkat. We
      found that binding of CD44+ Jurkat transfectants to HA requires cellular
      activation. Cellular activation induces the reorganization of the cytoskeleton
      proteins. Reorganization of cytoskeletal proteins results in clustering of CD44
      on the cell surface. Clustering of CD44 on the cell surface is a prerequisite for
      the homodimerization of CD44. Our studies on Jurkat transfectants and results
      from other investigators suggest that interactions between CD44 and HA is a
      dynamic process and requires the participation of different cellular components;
      depending of the nature of the cell type and/or the nature of the activation
      signals.

PMID- 9634639
TI  - Adventitial gene transfer to arterial wall.
AB  - Vascular gene transfer offers a promising alternative for the treatment of
      cardiovascular diseases. Blood vessels are among the easiest targets for gene
      therapy and in most conditions only a temporary expression of the transfected
      gene will be required to achieve a beneficial biological effect. Adenoviruses
      lead to most efficient transgene expression in arterial wall. Depending on the
      treatment requirements, gene transfer to the artery wall can be accomplished both
      from lumen and from adventitia. Promising therapeutic effects have been obtained
      in animal models of restenosis with the transfer of vascular endothelial growth
      factor (VEGF), nitric oxide synthase, thymidine kinase, retinoblastoma, growth
      arrest homeobox gene and antisense oligonucleotides against transcription factors
      or cell cycle regulatory proteins. First experiences of VEGF gene transfer to
      human peripheral arteries have also been reported. However, further studies
      regarding gene transfer techniques, vectors and safety of the procedures are
      needed before a full therapeutic potential of gene therapy in vascular diseases
      can be evaluated.

PMID- 9634640
TI  - Anticholinergic action of clonidine in rats with sinoaortic denervation.
AB  - A study was carried out relating to the anticholinergic action of clonidine on
      the cardiovascular responses to i.c.v. injection of neostigmine, a quaternary
      anticholinesterase, in conscious sham-operated animals and rats with sinoaortic
      denervation, 7 days after the corresponding operation. Neostigmine (0.1-1
      micrograms i.c.v.) induced a dose-dependent pressor and bradycardic responses in
      sham-operated rats but induced only an increase in blood pressure in sinoaortic
      denervated animals. However, the pressor response in sinoaortic-denervated rats
      was significantly greater than in sham-operated animals. Clonidine (10 micrograms
      kg-1 i.v.) induced a fall in mean arterial pressure in sinoaortic-denervated rats
      but not in sham-operated animals. Moreover, sinoaortic denervation reduced the
      bradycardic action of this antihypertensive drug. The anticholinesterase activity
      of clonidine (10 micrograms kg-1 i.v.), given 30 min previously, prevented the
      bradycardic action of neostigmine (0.1-1 micrograms i.c.v.) but failed to modify
      the pressor effect in sham-operated rats. This alpha2-adrenergic agent reduced
      the pressor response to i.c.v. administration of neostigmine in sinoaortic
      denervated rats. Alternatively, the i.c.v. administration of clonidine (3
      micrograms i.c.v.), given either 15 or 30 min before neostigmine, only prevented
      the bradycardic effect of the anticholinesterase (0.3 micrograms i.c.v.) in sham
      operated rats but not the pressor action of this drug. In sinoaortic denervated
      rats, 3 micrograms of clonidine i.c.v. reduced an increase in blood pressure by
      i.c.v. injection of the anticholinesterase. The results suggest different central
      cholinergic mechanisms and different cholinergic-adrenergic interactions on the
      cardiovascular responses elicited by centrally injected neostigmine in sinoaortic
      denervated rats.

PMID- 9634641
TI  - Screening of preformed oxidised low density lipoprotein isolated by a polyanion
      precipitation method. Its correlation with serum triglyceride levels.
AB  - For clinical and epidemiological screening a simple and sensitive methodology was
      developed for detection of preformed lipid peroxides (LPO) in low density
      lipoprotein (LDL). For this purpose, the iodometric assay of El-Saadani et al. (J
      Lipid Res 1989;30:627-30) was adapted to the fraction containing LDL isolated by
      polyanion precipitation avoiding ultracentrifugation. This fraction also includes
      intermediate density lipoprotein. Stratifying 53 individuals by their serum
      triglyceride levels (TG) the highest quartile showed a highly significant
      elevation of LDL-LPO compared with the lowest one (69.2 +/- 41.2 vs 22.9 +/- 10.0
      nmol mg-1 LDL-apo B, P < 0.001). LDL-LPO concentration also showed a strong
      correlation with TG (r = 0.73, P < 0.00001) and significant inverse correlations
      with high density lipoprotein cholesterol (HDL-C) and HDL3-C subfraction (r = 
      0.37, P < 0.01 and r = -0.38, P = 0.01, respectively). The TG/HDL-C ratio, which
      is closely associated with insulin resistance, was strongly correlated with LDL
      LPO (r = 0.83, P < 0.00001). Significant elevations of LPO were observed in
      phenotypic hyperlipoproteinemias (HLP) IIb and IV (P < 0.01 and P < 0.02,
      respectively) and when expressing LPO in mol/mol of LDL-apo B, two- and 2.5-fold
      higher values were found in types IIb and IV HLP, respectively, compared with
      normolipidemic subjects, suggesting a more oxidative environment for apo B in
      both phenotypes. No variations in LPO were found in type IIa HLP. This simple
      assay for in vivo detection of LDL-LPO, emphasises the possible atherogenic
      effect of TG through their oxidative capacity and suggests the integration of LPO
      to the cluster of associated risk factors: high TG, low HDL-C and insulin
      resistance.

PMID- 9634642
TI  - Different aspects of the effects of thapsigargin on automatism, contractility and
      responsiveness to phenylephrine in cardiac preparations from rats and guinea
      pigs.
AB  - Sarcoplasmic reticulum (SR) Ca(2+)-ATPase play a very important role in
      excitation-contraction coupling in the heart. The effects of thapsigargin (TG), a
      selective inhibitor of SR Ca(2+)-ATPase in the heart muscle, on automatism and
      contractility of the rat and guinea pig heart were examined. Experiments were
      performed on isolated right auricula and right ventricle papillary muscle. The
      following parameters were registered: force of contraction (Fc); rate of rise of
      force (+dF/dt); rate of fall of force (-dF/dt); time to peak contraction (ttp);
      duration of relaxation phase of contraction at the level of 10% of total
      amplitude (tt10); and automatism (b.p.m.). Additionally, the influence of
      thapsigargin on the effects of phenylephrine on the above mentioned parameters
      were studied. It was found that TG (1 microM) decreased only the automatism in
      rat heart, but increased automatism and ttp duration and decreased Fc in guinea
      pig heart. The positive force-frequency relation in the guinea pig heart was
      attenuated. The effects of phenylephrine in the rat heart were not significantly
      different before and after pretreatment with TG. Alternatively, pretreatment with
      TG exerted a profound influence on the effects of phenylephrine in the guinea pig
      heart. The results indicate that TG has different effects on the guinea pig and
      rat hearts. The reason for this could be due to species differences, i.e. the
      weaker crossing of TG through the membrane of rat myocytes or a different
      mechanism of Ca2+ homeostasis in rat and guinea pig hearts.

PMID- 9634643
TI  - Gastric cytoprotective activity of dehydroleucodine in rats. Role of nitric
      oxide.
AB  - Previously we reported that dehydroleucodine (DhL), a sesquiterpene lactone,
      shows gastric and duodenal cytoprotective activity. The mechanism is not mediated
      by antiacid secretory action; DhL stimulated mucus production and indomethacin
      pretreatment reduced cytoprotective action. In the present study we demonstrated
      that the gastric cytoprotective effect is antagonized by the nitric oxide (NO)
      synthase inhibitor, NG-nitro-L-arginine. The inhibitory action of NG-nitro-L
      arginine is reversed by L-arginine, but not D-arginine. The findings suggest that
      NO is involved in the gastroprotection induced by DhL.

PMID- 9634644
TI  - Experimental approaches for observing homologous desensitisation and their
      pitfalls.
AB  - Whereas molecular mechanisms of cell desensitisation have been discussed at
      length in the literature, little organised information on the methods for
      studying desensitisation of cellular responses has been published. In this
      article, three commonly utilised protocols for studying homologous
      desensitisation of cellular responses are evaluated. These are (1) observation of
      attenuation of a response after an initial stimulus-induced activation, (2)
      repeated stimulation of cells after washing away the previous stimulus, and (3)
      repeated stimulation without a wash step. Advantages and limitations of each
      protocol are discussed and data is presented demonstrating some of the properties
      of the protocols.

PMID- 9634645
TI  - Inhibition of wound-induced expression of transforming growth factor-beta 1 mRNA
      by its antisense oligonucleotides.
AB  - Transforming growth factor-beta 1 (TGF-beta 1) is a member of a gene superfamily
      that regulates proliferation, differentiation and other functions in many cell
      types. To gain insight into the role of TGF-beta 1 in wound repair, we have
      analysed the ability of an antisense TGF-beta 1 oligodeoxynucleotides (ODN) to
      specifically inhibit wound-induced expression of TGF-beta 1 mRNA in the mouse
      skin. Although injury induced the expression of TGF-beta 1 mRNA at the wound
      sites, expression of TGF-beta 2-or TGF-beta 3-mRNA was not detected. In
      comparison to the 24 h following injury, higher levels of TGF-beta 1 mRNA
      expression were observed in the wound sites after 72 h. Northern blotting and in
      situ hybridisation analysis showed that wound sites treated with antisense TGF
      beta 1 ODN exhibited no detectable levels of TGF-beta 1 mRNA after injury,
      whereas the sites treated with sense TGF-beta 1 ODN possessed significant amounts
      of its mRNA. Our results demonstrated that antisense TGF-beta 1 ODN inhibited the
      wound-induced expression of TGF-beta 1 mRNA in vivo.

PMID- 9634646
TI  - Tolerance develops to the antinociceptive and motor impairing effects of ACEA
      1416, a NMDA receptor antagonist, in the formalin and rotarod test in mice.
AB  - Antinociception, disturbances of motor coordination and development of tolerance
      to these effects were examined following acute and chronic administration of ACEA
      1416, a NMDA receptor/glycine site antagonist, in Swiss Webster mice using the
      formalin and rotarod tests. In the formalin test, mice were injected with either
      the vehicle (Tris, 0.05 M) or ACEA-1416 (1-10 mg kg-1). Fifteen or 60 min later,
      mice were injected with formalin and observed for nociceptive responses (licking
      and/or biting of the injected paw). In the vehicle-treated control mice a
      biphasic nociceptive response was observed at 0-5 min (early phase) and from 15
      to 50 min (late phase) after formalin injections. ACEA-1416 showed a dose
      dependent attenuation of the nociceptive responses in both phases of the formalin
      test. In the rotarod test, mice were injected with ACEA-1416, placed on a
      rotating bar at 6 rpm for 2 min and examined for motor impairments. ACEA-1416
      produced disturbances of motor coordination in a dose-dependent manner. For
      tolerance studies, mice were injected once daily with either the vehicle or ACEA
      1416 (30 mg kg-1) and tested for antinociception and motor impairment on day 5,
      10 and 20. A time-dependent decrease in the antinociceptive effect of the drug
      was observed in the early but not in the late phase of the formalin test.
      Tolerance also developed to the motor impairing effect of the drug. Taken
      together, these data suggest that chronic inhibition of NMDA receptors by ACEA
      1416 differentially affected the antinociceptive effect of the drug in the early
      and late phase of the formalin test. Furthermore, the antinociceptive and motor
      impairing effects of the drug can be separated.

PMID- 9634647
TI  - Taste conditioning effects of buprenorphine in morphine-naive and morphine
      experienced rats.
AB  - Male Sprague-Dawley rats were injected daily with saline (morphine-naive rats) or
      20 mg kg-1 morphine (morphine-experienced rats), starting 15 days before the
      experiment. Subsequent taste conditioning indicated that 0.1 mg kg-1
      buprenorphine significantly decreased 0.025% saccharin consumption in morphine
      naive, but not in morphine-experienced rats. A 10 mg kg-1 dose of morphine gave
      similar results, while d-amphetamine (0.75 mg kg-1) was consistently aversive. It
      was concluded that morphine experience selectively blocks the aversive effects of
      buprenorphine in rats; thus it possibly increases the potential for buprenorphine
      abuse.

PMID- 9634648
TI  - Dose-dependent pancreatotrophic effect of cholecystokinin-octapeptide in the rat:
      the influence of starvation.
AB  - Cholecystokinin (CCK) and its analogues are known to exert trophic effects on the
      exocrine pancreas, whereas at high doses, they produce pancreatic injury. This
      study was carried out to study the effect of starvation on the dose-dependent
      pancreatotrophic effect of CCK-8 in rats. Normal or fasted rats were treated with
      CCK-8 doses ranging from 0.5 to 32 and 0.5 to 8 micrograms kg-1, respectively,
      twice daily for 5 days. Pancreatic size, protein, DNA, secretory enzyme and
      trypsin inhibitor (PSTI) contents as well as histology were examined. In normal
      rats, CCK-8 increased the pancreatic content of protein, amylase, serine
      proteases and PSTI with maximum values between doses of 2 and 16 micrograms kg-1.
      The dose of 32 micrograms kg-1, however, yielded less trophic responses. Given to
      fasted rats, CCK-8 increased the weight as well as protein and secretory enzyme
      contents of the pancreas with maximum values between doses of 1 and 4 micrograms
      kg-1. The first dose supramaximum for the trophic responses was as low as 8
      micrograms kg-1. Histology revealed necroinflammatory damage (acinar cell
      vacuolization, focal cell necrosis) in the exocrine pancreas at supramaximum
      doses of CCK-8 in both groups. Cell necroses and vacuolization were less but
      present even at doses optimum for trophism and exhibited dependence on both the
      dose of CCK-8 and nutrition. In either the normal or fasted animals, the
      periinsular acini were relatively less affected by the toxic effects of CCK-8
      than the teleinsular ones. The results indicate that starvation makes the
      exocrine pancreas more sensitive to necroinflammatory effects of CCK-8. The
      relative protection seen in periinsular acini suggests a modulatory influence of
      islet hormones on development of CCK-induced acinar cell injury.

PMID- 9634649
TI  - Swiss regulations for controlling clinical trials.
AB  - Switzerland has recently issued regulations designed to control all trials with
      drugs in human subjects, namely the 'Regolamento dell'Ufficio Intercantonale per
      il controllo dei medicamenti in fase di studio clinico' (Intercantonal
      Regulations Controlling Drugs used in Clinical Trials), which have been operating
      since 1st January 1995. These new regulations are generally consistent with other
      international regulations and have introduced the concept of good clinical
      practice (GCP) into Switzerland. There are other regulations in Switzerland, such
      as Federal regulations on immunobiological products, special rules governing the
      administration of radiolabelled drugs to humans, drugs of abuse and medical
      devices. Any gap in the central regulations must be filled by cantonal
      regulations, where they exist. This is a comprehensive review of the regulations
      governing clinical trials in Switzerland, with special attention being devoted to
      trials with therapeutic compounds and to compatibility between Swiss and
      international procedures.

PMID- 9634650
TI  - Protein identification in the post-genome era: the rapid rise of proteomics.

PMID- 9634651
TI  - From membrane to molecule to the third amino acid from the left with a membrane
      transport protein.
AB  - The lac permease of E. coli is a paradigm for secondary active transporter
      proteins that transduce the free energy stored in electrochemical ion gradients
      into work in the form of a concentration gradient. This hydrophobic, polytopic,
      cytoplasmic membrane protein catalyses the coupled, stoichiometric translocation
      of beta-galactosides and H+, and it has been solubilized, purified, reconstituted
      into artificial phospholipid vesicles and shown to be solely responsible
      responsible for beta-galactoside transport as a monomer. The lacY gene which
      encodes the permease has been cloned and sequenced, and all available evidence
      indicates that the protein has 12 transmembrane domains in alpha-helical
      configuration that traverse the membrane in zigzag fashion connected by
      hydrophilic loops with the N and C termini on the cytoplasmic face of the
      membrane. Extensive use of site-directed and Cys-scanning mutagenesis indicates
      that very few residues in the permease are directly involved in the transport
      mechanism, but the permease appears to be a highly flexible protein that
      undergoes widespread conformational changes during turnover. Based on a variety
      of site-directed approaches which include second-site suppressor analysis and
      site-directed mutagenesis, excimer fluorescence, engineered divalent metal
      binding sites, chemical cleavage, EPR, thiol crosslinking and identification of
      discontinuous mAb epitopes, a helix packing model has been formulated.A mechanism
      for the coupled translocate ion of substrate and H+ by the lac permease of E.
      coli is proposed. Four residues are irreplaceable with respect to coupling, and
      the residues are paired in the tertiary structure--Arg-302 (helix IX) with Glu
      325 (helix 10) and His-322 (helix 10) with Glu-269 (helix VIII). In an adjacent
      region of the molecule at the interface between helices VIII and V is the
      substrate translocation pathway in which Glu-126 and Arg-144 appear to play key
      roles. Because of this arrangement, interfacial changes between helices VIII and
      V are transmitted to the interface between helices IX and X and vice versa. Upon
      ligand binding, a structural change at the interface between helices V and VIII
      disrupts the interaction between Glu-269 and His-322, Glu-269 displaces Glu-325
      from Ag-302 and Glu-325 is protonated.Simultaneously, protonated Glu-325 becomes
      inaccessible to water which drastically increases its pKa. In this configuration,
      the permease undergoes a freely reversible conformational change that corresponds
      to translocation of the ternary complex. In order to return to ground state after
      release of substrate, the Arg-302-Glu-325 interaction must be reestablished which
      necessitates loss of H+ from Glu-325. The H+ is released into a water-filled
      crevice between helices IX and X which becomes transiently accessible to both
      sides of the membrane due to a change in helix tilt, where it is acted upon
      equally by either the membrane potential or the pH gradient across the membrane.
      Remarkably few amino-acid residues appear to be critically involved in the
      transport mechanism of lac permease, suggesting that relatively simple chemistry
      drives the mechanism. On the other hand, widespread, cooperative conformational
      changes appear to be involved in turnover. As a whole the data suggest that the
      12 helices which comprise the permease are loosely packed with a considerable
      amount of water in the interstices and that surface contours are important for
      sliding or tilting motions that occur during turnover. This surmise coupled with
      the indication that few residues are essential to the mechanism is encouraging in
      that it suggest that the possibility that a relatively low resolution structure
      (i.e. helix packing) plus localization of the critical residues and the
      translocation pathway can provide important insights into the mechanism.
      (ABSTRACT TRUNCATED)

PMID- 9634652
TI  - Infrared spectroscopy of proteins and peptides in lipid bilayers.

PMID- 9634653
TI  - [Obtention and characterization of murine beta-NGF. Application in a model of
      cerebral aging].
AB  - INTRODUCTION: beta-NGF is a basic protein of 118 aminoacids which acts are a
      trophic factor for sensory and sympathetic neurons of the peripheral nervous
      system, and on cholinergic neurons of the anterior basal cerebrum. OBJECTIVES: In
      view of the functional effect of beta-HGF and its possibilities as a therapeutic
      agent in neurodegenerative disease, including Alzheimer's disease in this study
      our aim was to obtain, characterize and show the main results of the application
      of beta-NGFm in a model of cerebral ageing in rats with cognitive disorders.
      MATERIAL AND METHODS: For the obtention of beta-NGFm we followed Mobley's method
      as modified by Ebendal and used mouse submaxillary gland as a source of raw
      material. The characterization studies were carried out by application of seven
      techniques which allowed physicochemical characterization and demonstration of
      the biological activity of the product. Application of beta-NGF obtained under
      these conditions was carried out in a mode of cerebral ageing and the effects of
      treatment were assessed by conduct studies, measurement of the activity of the
      enzyme acetyl cholinesterase and study of neural plasticity. CONCLUSIONS:
      Characterization studies carried out on the beta-NGFm showed that the protein
      obtained consists of a mixture of molecules of beta-NGFm which are intact at
      their extreme N-Terminal, and molecules which have lost the octapeptide of the N
      terminal position and show some modification increasing hydrophobicity. All these
      species were recognized immunologically by the specific antibody anti-NGFm and
      showed biological activity.

PMID- 9634654
TI  - [Clinical characterization of patients with multiple sclerosis defined in Cuba].
AB  - INTRODUCTION: Since 1975 no studies have been done in Cuba defining the clinical
      characteristics of patients with multiple sclerosis (MS). OBJECTIVE: To describe
      the characteristics of a group of Cuban patients with definite clinical MS.
      MATERIAL AND METHODS: Fifty eight patients with definite clinical MS were studied
      (Poser et al) with normal motor (VCM) and sensory (VCS) conduction velocities.
      Tests were done on them: clinical scale (Scripps), incapacity (EDSS) and quality
      of life (Steps), together with various complementary tests. Each patient was
      classified according to the way in which the disease evolved. Also the two
      commonest clinical types were compared and we applied the difference test between
      percentages of non-paired samples with an alfa level of 0.05. RESULTS: Onset of
      the illness in most cases was before the age of 40 (86.1%), 75.9% were women and
      82.8% were white. In 15.3% there was a family history of MS. In 25.9% there were
      psychiatric disorders and trigger factors (43.1%. The most frequent initial
      symptoms were pyramidal (48.3%) sensorial (41.4%) and cerebellar (39.7%). Scripps
      scale scores were < 80 in 60.2%, in EDSS < 5 (61.9%) and in the Clinical Steps <
      3 in 65.4%). Motor potentials (81.9%) somatosensory potential (PESS) (72.3%) and
      magnetic resonance imaging (MR) (76.4%) were the most abnormal results.
      Exacerbation-remission (ER) was the most frequent type of evolution (53.4%)
      generally affecting patients aged under 40 years old (p = 0.02), EDSS < 5
      (64.4%), Scripps > 80 (61.2%), Steps < 3 (95.6%), pyramidal system involvement
      (58.5%), cerebellar (29.2%) and MRI abnormality (80%). The progressive primary
      form (PP) was the second most frequent (29.3%); 29.4% were under 40 years of age,
      had more marked changes in all functional system (100%), degree of incapacity and
      quality of life (100%). PESS (92.5%); the urodynamic tests 58.85%) were less
      positive on MRI (54.5%) as compared with the ER form. CONCLUSIONS: The
      differences found between the clinical forms ER and II indicate that there is
      greater deterioration in the PP form, probably due to age and more cerebellar and
      spinal cord involvement.

PMID- 9634655
TI  - [Deficiency, disability and handicap in multiple sclerosis: a population-based
      study in Valladolid].
AB  - INTRODUCTION: Apart from impairment there is hardly any other assessment of the
      repercussions of multiple sclerosis (MS) in population studies. OBJECTIVE: To
      analyze the functional state of en epidemiological series of patients in the
      Valladolid health district. MATERIAL AND METHODS: A descriptive transversal study
      of a geographically defined population base. During a period of three months and
      complementing a prevalence study, were assessed, by means of the Minimal Record
      of Disability, impairment, disability and handicap in a series of 51 patients (33
      women and 18 men) with clinically defined MS, who lived in the area on 1 March
      1997. RESULTS: There was a primarily progressive evolution in 21.6% of the
      patients, and secondarily progressive in 11.8%. Average follow-up time was 9.1
      years (range 1-41) and average age of onset 27.8 years (range 14.7-51.0). The
      distribution of scores on the Expanded Disability Status Scale was bimodal
      (average and interquartile range: 3.0 (1.5-5.0). 80.4% of the patients continued
      to be ambulatory. 21.5% had frequent urinary incontinence or required a long-term
      urinary catheter. Less than 20% needed help with day to day activities. 78% of
      the patients complained of some degree of fatigue, and 51% had difficulties with
      social relationships. 59.4% of the patients had full-time jobs and 70.6% had no
      financial problems. CONCLUSIONS: The study shows that the functional state of
      persons with MS is better than was thought, and that assessment of the
      consequences of this illness should include disability and handicap profiles.

PMID- 9634656
TI  - [Follow-up of partial seizure progression in an infant].
AB  - OBJECTIVE AND MATERIAL: We are carried out a retrospective study of 43 patients,
      21 males and 22 women entered during the period of infancy in the Service of
      Neurology of our hospital and with diagnostic of any type of partial seizure, in
      an intent to correlate a series of clinical parameters, electroneurophysiologics
      and initial therapeutics with their factors follow-up periods. RESULTS: They are
      a half age of 7.11 months (1-19), consecutive being controlled for a period of
      time of 40 months (6-96). We have settled down a relationship between the drugs
      utilized in the first seizure and that other that they remained in their last
      revision, the current state of the critical manifestations, and the existence or
      not of an agreement between the e diagnosis emitted to the discharge and the
      development of the illness. CONCLUSION: After the present study, we thought that
      the current classification of the epileptic seizures is insufficient in the age
      of the infant, with presages much more complexes.

PMID- 9634657
TI  - [Comparison of the multifactorial model as a hereditary mechanism of non
      myoclonic generalized idiopathic epilepsy and partial idiopathic epilepsy].
AB  - OBJECTIVE AND METHODS: An experimental study about the predictions from the
      multifactorial threshold model created by Falconer is presented, assuming that
      this model may explain the genetic mechanisms underlying the family aggregation
      of idiopathic epilepsies. RESULTS: We failed to confirm the following predictions
      from the falconer model: decreased prevalence of disease in relatives,
      proportional to decreased family links, and the order of birth effect. An
      heredity greater than 100% was calculated which is concordant with the presence
      of at least a locus with a major gen affect. CONCLUSION: Our results reject the
      multifactorial threshold effect and suggest the presence of a major gen or
      Mendelian effect. An analysis of complex segregation is suggested for future
      studies.

PMID- 9634658
TI  - [Nerve growth factor and neurological diseases].
AB  - INTRODUCTION: The effects of Nerve Growth Factor (NGF) within and outside the
      nervous system have been amply discussed in recent decades. Recently clinical
      studies have shown the effectiveness of this growth factor in the treatment of
      neurodegenerative disorders. This clinical use makes it necessary to have
      sensitive, specific methods available to permit measurement of the level of this
      protein and to determine how it behaves during the course of treatment.
      OBJECTIVE: To describe the measurement of NGF levels in human serum using an
      immunoenzymatic method and evaluating the levels of this protein in some
      neurological disorders. Materials and methods. NGF levels were measured in the
      serum of healthy persons and in patients with Alzheimer's disease (AD)
      Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis
      (MS) and Huntington's chorea (HC) using a double site immune-enzymatic assay.
      Murine 27/21 anti-beta-NGF monoclonal antibody was used as the antibody to cover
      the plate and as conjugate. RESULTS: Adding a block pass to the method, in which
      the sample was incubated with an excess of 27/21 antibody effectively reduced the
      signal observed in the immuno-enzymatic assay. A moderate reduction in beta-NGF
      levels was seen in the serum of patients with ALS and MS. There was a
      statistically significant reduction in the patients who were carriers of PD and
      HC. CONCLUSIONS: The significant reduction in NGF levels in patients with PD and
      HC may be associated with a disorder in the use of this protein in central and
      peripheral tissues.

PMID- 9634659
TI  - [Cerebral venous thrombosis in the region of Murcia].
AB  - INTRODUCTION AND OBJECTIVE: Massive usage of new neuroimaging techniques has
      produced an increase in the number of patients with cerebral venous thrombosis.
      Our aim has been to evaluate this shift in our county through the clinico
      radiologic characteristics of the patients admitted to our unit. MATERIAL AND
      METHODS: Over the last 7 years a total of 12 patients suffering from cerebral
      venous thrombosis were attended in our department. We have analyzed
      retrospectively their clinical records. RESULTS: There were 11 women 1 man with a
      range of ages from 13 to 60 years old. The main associated factor was oral
      contraceptives intake. Most of them presented with symptoms of benign
      intracranial hypertension. Magnetic resonance imaging was the most sensitive
      diagnostic tool. Outcome was good in general. Most of them were treated with
      intravenous heparin during the acute phase and received oral anticoagulation for
      6 months. More than half were diagnosed all over the last three years.
      CONCLUSIONS: Our data seem to confirm this tendency towards a larger number of
      cases with the application of new diagnostic tools. In these cases, clinical
      course is more benign than reported in classical series.

PMID- 9634660
TI  - [Neonatal sciatic palsy: etiology and outcome of 21 cases].
AB  - INTRODUCTION: Sciatic nerve paralysis is a rare entity in the newborn. Few
      reference in specialized tests indicate that in the majority of cases the sciatic
      palsy has been observed after misplaced injections into the buttocks. The
      prognosis is variable and appears to be better after umbilical vessel
      catheterization for injection of medications than after misplaced muscular
      injections. In case of recovery it takes place within 3 to 12 months. OBJECTIVE:
      The objective of the present study is to know the evolution of neonatal sciatic
      palsy and to determine their injury noxe in regard to perinatal factors, and
      their relationship with long-time outcome, and to look for prognostic clues of
      clinical utility. MATERIAL AND METHODS: We evaluated perinatal factors of newborn
      children with sciatic nerve paralysis, followed for more than 18 months of
      clinical evolution, in a neuropediatric centre. RESULTS: Twenty one newborn with
      such criteria were evaluated. Gestational age was within 32 and 42 weeks (median
      38.2). The birth weight was between 2,100 and 4,100 g (median 2,973). The
      majority of cases obtained total recovery (16 of 21). The time of recovery was 4
      to 14 months (median 8.8). Free ambulation was obtained by all cases (at 10 to 24
      months). No apparent cause was observed in the majority of cases. Cesarean
      delivery was more frequent specially in cases with permanent consequences.
      CONCLUSION: Long-time prognostic of neonatal sciatic palsy is generally good. In
      our series all the cases with consequences were associated to cesarean delivery.
      The duration of cesarean intervention and the anesthesic hypotony of the newborn
      could be implicated in the sciatic nerve injury of poor outcome.

PMID- 9634661
TI  - [Tables of normal values of average and long latency auditory potentials].
AB  - INTRODUCTION AND OBJECTIVE: In view of the disparity of data and methodology
      concerning medium (MAEP) and long latency (LAEP) acoustic evoked potentials, we
      have obtained tables of normal values using a reliable method and statistical
      study of these potentials in 30 healthy persons, in order to serve as a basis for
      clinical reference and for possible further studies. MATERIAL AND METHODS: In the
      MAEP we used the two types of stimuli most commonly employed, first a click and
      then a rising-plateau-falling tone (2-6-2). We observed that this did not affect
      the latency or amplitude of the different waves, although the best defined waves
      are obtained with tones. In the LAEP we always used a tone with rise-plateau-fall
      of 10-50-10, as recommended by the American Electroneurophysiological Society. In
      all cases the intensity was of 70 db, with rarefaction and masking of the
      contralateral ear with an intensity of 50 db. Self-adhesive electrodes were used
      for captation; the active one was placed on the ipsilateral ear lobe and the
      reference electrode in Cz for the LAEP. For the LAEP the lower filter was of 1 Hz
      and the higher of 70 Hz. In view of the variety of filters recommended, 10 Hz at
      the lower level and 500, 1000 and 2000 at the higher level were used successively
      for the MAEP. We observed that these did not affect the latency or amplitude of
      the waves, so these three values may all be used equally well. RESULTS AND
      CONCLUSIONS: In the inter-sexual study, no differences were seen between men and
      women. Nor were there significant differences between the acoustic evoked
      potentials on the right and left sides of the same person.

PMID- 9634663
TI  - [Giant intraventricular arachnoid cyst: report of 2 cases].
AB  - INTRODUCTION: It is very unusual to find cysts situated intraventricularly. Only
      24 cases have been described to date in the literature. CLINICAL CASES: In this
      paper we present two new cases considering that because of their exceptional size
      they deserve to be called 'giant'. The two patients had been diagnosed as having
      epilepsy during childhood or youth. No neuroradiological studies had ever been
      done. The cause of hospital admission in the first case was headache and vomiting
      and in the second case a convulsive crisis. We did cerebral CT scans in both
      cases and a MR control scan in the second case. This formed the basis for our
      diagnosis. Unlike previous cases they were not operated on. Their clinical course
      may be considered satisfactory to date, since there have been no further
      convulsive crisis nor other neurological alterations. We have therefore been
      conservative with regard to the indication for surgery in these patients.
      CONCLUSIONS: Review of the literature does not completely clarify the origin of
      these lesions but we are inclined to believe that there is an intimate
      relationship between the formation of an intraventricular arachnoid cyst and the
      choroid plexus. Many new cases will have to be diagnosed before we can fully
      understand the true physiopathology of these cysts.

PMID- 9634662
TI  - [Diagnosis in severe myoclonic epilepsy in childhood: study of 13 cases].
AB  - OBJECTIVE: The purpose of this report is to describe clinical pattern, EEG,
      outcome and differential diagnosis in severe myoclonic epilepsy in infancy
      (SMEI). MATERIAL AND METHODS: We report 13 cases initially diagnosed of SMEI and
      selected according to the following criteria: first seizure between 1 and 12
      months of life, frequent seizures resistant to antiepileptic drugs, no previous
      personal history of disease, normal psychomotor development before the first
      seizure and normal EEG, CT scanning and laboratory analyses at the beginning. CT
      and/or MRI were performed in 13 cases, arteriography in 2 patients, MR
      spectroscopic imaging in 1 child and SPECT in 3 cases. Quantification of
      enzymatic activities of the mitochondrial respiratory chain was made in 5
      patients. RESULTS: Only 8 cases were finally diagnosed of SMEI according to ILAE
      definition. In two cases, seizures were finally controlled with antiepileptic
      treatment and EEG abnormalities disappeared. Three patients showed other
      findings: mesiotemporal sclerosis, angiitis diffusely involving CNS and
      mitochondrial cytopathy with deficiency of the complex IV. CONCLUSIONS: Although
      diagnosis of SMEI, based on clinical manifestations, is suspected in most cases
      from the first year of life, final diagnosis should not be confirmed until steady
      state, when polymorphous seizures occur. Even then, differential diagnosis should
      be made with other disorders. Perhaps, further studies should be performed in
      order to identify and eliminate another etiology.

PMID- 9634664
TI  - [Usefulness of the EEG recording in the diagnosis of cyclosporin A-induced
      encephalopathy].
AB  - INTRODUCTION: Cyclosporine A is one of the immunosuppressors most frequently used
      to prevent transplant rejection. Neurotoxicity is one of the complications often
      associated with it. These complications include acute encephalopathy, lethargy,
      confusion state, tremor, headache, motor disorders, visual changes and epileptic
      crises amongst others, even when blood levels are at what are considered to be
      'therapeutic' levels. CLINICAL CASES: We present the EEG anomalies found in 3
      transplant patients (two liver transplants and on double lung transplant) to whom
      cyclosporin A had been given and who presented with status epilepticus. The EEG
      recordings showed paroxystic discharges of focal onset in the temporo-occipital
      areas. They were mainly correlated with the clinical findings of oculomotor and
      eyelid disorders. CONCLUSION: The topography of the neurophysiological findings
      supports--as do the other clinico-radiological findings--localization preferably
      to the posterior areas of cerebral dysfunction associated with cyclosporin A.
      Although the physiopathological origin of the encephalopathy of patients treated
      with cyclosporin A seems to correspond to multiple factors, we wish to point out
      the diagnostic usefulness of the identification of EEG changes localized to the
      temporo-occipital areas in the recognition of the neurotoxic syndrome in these
      patients.

PMID- 9634665
TI  - [Neurocutaneous melanosis].
AB  - INTRODUCTION: Neurocutaneous melanosis is an infrequent condition characterized
      by the presence of numerous gigantic cutaneous naevi and melanocytic infiltration
      of the central nervous system and/or the leptomeningeal layers. Different
      clinical features may be seen: endocranial hypertension due to hydrocephalus,
      cranial nerve paralysis, myelopathy, convulsive seizures, etc. The prognosis is
      considered to be malignant. Only positive CNS histological findings confirm the
      diagnosis. CLINICAL CASE: We present the case of a man with cutaneous lesions
      compatible with the diagnosis of neurocutaneous melanosis since birth, with
      benign self-limiting epilepsy in early childhood. Cerebral CT and MR scans were
      normal until the age of 17, when hipper-signal lesions appeared on MR,
      infiltrating the leptomeninges of the deep temporal pole and anterior aspect of
      the cerebral peduncles, which suggested the presence of melanocytes in the CNS.
      CONCLUSIONS: There are cases of neurocutaneous melanosis with a good medium-term
      prognosis and benign manifestations until infiltration of the CNS occurs. Then
      they start to show the classical behavior of cases with a malignant prognosis. MR
      should be included as part of the diagnostic criteria for neurocutaneous
      melanosis. MR should be done periodically in patients with cutaneous lesions
      suggestive of this condition.

PMID- 9634666
TI  - [Munchausen syndrome by proxy: report of one case with epilepsy].
AB  - INTRODUCTION: Munchausen syndrome by proxy (MSBP) is a rare form of child abuse
      in which a parent, usually the mother, fabricates or produces illness in a child,
      so causing them unnecessary medical investigations, treatments and
      hospitalizations. One of the commonest false presenting symptom is 'seizures'.
      CLINICAL CASE: An eight years old boy with Munchausen syndrome by proxy is
      reported. This child had had genuine seizures well controlled by standard
      anticonvulsant treatment at the start of the false illness. At the age of seven
      years, the patient showed very frequent seizures. The child was treated with
      antiepileptic drugs, but treatments were ineffective and seizures continued.
      Results of multiple tests, including an extensive blood chemistry analyses, CT,
      MRI, SPECT, were normal. Electroencephalogram showed posterior slow waves. Acute
      neurological deterioration was observed six weeks after hospitalization and it
      was finally proved that seizures were caused or triggered by clomipramine
      poisoning given by her mother. CONCLUSIONS: MSBP frequently presents as epileptic
      seizures in these abused children. MSBP diagnosis is more difficult to be made if
      true seizures exists with multiple fictitious seizures. Pediatrician should be
      alerted to the possibility of MSBP when seizures are poorly controlled,
      treatments are ineffective and there is no neurophysiologic dysfunction. Early
      diagnosis and intervention are essential because high mortality and psychologic
      morbidity are associated with this syndrome.

PMID- 9634667
TI  - [Neuroimaging of hypoglycemia].
AB  - INTRODUCTION: Sustained hypoglycemia causes serious cerebral damage. The cortex,
      hippocampus and basal ganglia are particularly vulnerable to this. Exceptionally,
      there have been communications regarding neuroimaging visualization of cerebral
      lesions attributable to hypoglycemia only. We present the case of a woman who
      suffered hypoglycemic coma with permanent neurological damage. Lesions were seen
      on magnetic resonance (MR) and cranial computerized tomography (CT). CLINICAL
      CASE: A 22 year old woman with no vascular risk factors was admitted to hospital
      in hypoglycemic coma, after attempting suicide with oral antidiabetic drugs. The
      duration of the coma was unknown. On admission the glycaemia was 28 mg/dl.
      Cranial CT scan was normal during the first 24 hours. Cerebral MR scan one week
      late showed hyperintense lesions in T2, basal ganglia and left hippocampus. The
      cranial CT scan one year later showed diffuse atrophy, with bilateral lesions of
      low attenuation in the basal ganglia and dilatation of the ventricular system.
      CONCLUSIONS: It is unusual to see lesions secondary to hypoglycemia on
      neuroimaging investigations. The etiopathogenic mechanism is still unknown and it
      has generally been described in diabetic patients. In our case these lesions can
      only be attributed to hypoglycemia. MR is more sensitive than cranial CT scan for
      the detection of these lesions during the acute phase.

PMID- 9634668
TI  - [A 56-year-old man with weakness of the legs].

PMID- 9634669
TI  - [Cerebrovascular disease in young adults. A study of its course in 167 patients].
AB  - INTRODUCTION: Few studies have been made of the prognosis of ictus in the young
      adult. The objective of this paper is to study the short term evolution of 167
      patients, aged between 15 and 45 years, with cerebral vascular disease. MATERIAL
      AND METHODS: Since 1986 a protocolized study has been made of all patients aged
      between 15 and 45 who were admitted to the Neurology Department of the Hospital
      General Universitario in Valencia for a cerebral vascular incident. The results
      obtained up to 1993 have been recorded in a data base. In this paper the
      demographic data and information as to intrahospital evolution have been used
      with the Canadian, modified Rankin and Barthel Scales in the various ictus
      groups. RESULTS: 28.7% of the patients were AIT and 71.3% were diagnosed as
      established ictus, of whom 38.8% were haemorrhagic and 61.2% were ischaemic.
      29.8% of the HIP, 33.3% of the embolic infarcts and 18.2% of the atherothrombotic
      infarcts were severely disabled on discharge from hospital. Mortality was 4.2%
      when AIT were excluded. DISCUSSION: Most studies are basically aetiopathological
      and much fewer include evaluation of prognosis. In our series, the patients had a
      satisfactory clinical course and low short-term mortality. As in the other
      series, the two groups with the worst prognosis were the HIP and the
      cardioembolic infarcts. Patients with HSA and HIV made outstandingly good
      progress.

PMID- 9634670
TI  - [Time for cerebral damage due to hyperglycemia in acute ischemia].
AB  - INTRODUCTION: Hyperglycemia increases morbimortality in cerebral infarcts. In
      animal models, this relationship is only seen during the initial moments of
      cerebral ischaemia. The time needed in humans for cerebral damage to occur due to
      hyperglycemia is not known. MATERIAL AND METHODS: We included 194 patients
      admitted within 24 hours of the start of their first clinical episode of cerebral
      hemisphere infarction. The glucemia was determined on admission and after 24, 48
      and 72 hours. The neurological defect was evaluated on the Canadian scale on the
      seventh day. The volume of the infarct was determined on a second CT scan done
      between the fourth and seventh days after the episode. RESULTS: There was a
      positive association between the volume of the infarct and the glycemias on
      admission and after 24 hours, but this was not seen in later determinations. The
      difference in scoring, on the Canadian scale, on the seventh day, between
      patients with glycemias above or below 120 mg/dl decreased from the time of
      admission up to the time samples were taken 72 hours later. However, statistical
      significance persisted during the whole period studied. Nevertheless, in a
      logistic regression model, the glycemia on admission was the only determination
      associated with the Canadian scale on the seventh day (OR = 1.02; IC 95% = 1.01
      1.02). CONCLUSIONS: There is a clear association between hyperglycemia and the
      worst stage of the infarct, and this is most intense in the first hours after
      onset of the clinical features.

PMID- 9634671
TI  - [Endovascular treatment of dural arteriovenous fistulas with medullary venous
      drainage. Experience with 18 patients].
AB  - INTRODUCTION AND OBJECTIVE: The authors report a series of 18 patients with
      myelopathy who were diagnosed of dural arteriovenous fistulas with venous
      medullary drainage (DFVMd). Purpose was to assess the effectiveness, initial and
      long term, of embolization, as the initial treatment, using polyvinyl alcohol
      particles (PVA) and liquid adhesives. N-butyl-cyanoacrylate (NBCA). MATERIAL AND
      METHODS: Magnetic resonance images were obtained in all patients showing spinal
      cord tissue changes consistent with an isquemic process secondary to venous
      hypertension. All 18 patients showed initially an improvement in clinical
      symptoms, demonstrating previous MR images resolution. RESULTS: The neurological
      status of 8 patients subsequently deteriorated with angiographically proven
      recurrences of their DFVMd. These patients underwent a second successful
      embolization procedure using NBVA. PVA embolization is long term ineffective and
      is not without risk. Endovascular treatment is less invasive than surgery, its
      morbidity is less, and it ensures earlier recovery for the patients. If
      embolization has failed, surgery can still be done. CONCLUSIONS: We recommend
      that NBVA embolization be the initial treatment of choice for DFVMd if referring
      the patient to an experienced interventional Neuroradiology unit is available.
      Careful clinical and neurologic examination is necessary to establish the
      diagnosis of DFVMd. Finally, we strongly recommend that patients be followed
      closely and aggressively. Periodic clinical and radiologic assessments, including
      MR and spinal angiography, are essential to achieve complete cure.

PMID- 9634672
TI  - [Cardiac disease in intracerebral hematomas].
AB  - INTRODUCTION AND OBJECTIVE: The Central Nervous System (CNS) plays an essential
      role in the regulation of the cardiac function. There is strong evidence that
      many CNS lesions, mainly those of hemorrhagic origin, may induce repolarization
      abnormalities and enlargement of the QT interval (ECG changes) and several types
      of arrhythmias. In some cases these changes have been related to sudden death.
      The imbalance between the sympathetic and parasympathetic systems, favoring the
      former, seems to be the etiopathogenic factor. MATERIAL AND METHODS: We have
      carried out a study on thirty-two in-patients suffering from non-severe
      intracerebral hemorrhage, by means of a Holter ECG examination within the first
      72 hours and a second record after two months. We have assessed any significative
      differences on the ECG findings in relation to the location of the hematoma (left
      or right hemispheres) and the presence of a personal history of arterial
      hypertension and/or heart disease. RESULTS: One or more ECG changes were present
      in 69.2% of the patients and 73% showed one or more rhythm abnormalities. There
      was a higher incidence of supraventricular arrhythmias associated with the right
      hemisphere hematomas, with an statistical significance for the atrial
      extrasystolia. No differences were found between the group with a previous
      history of hypertension and/or heart disease and the one without these
      conditions. There were two cases of sudden death, both with left hemisphere
      hematomas, and in one of them the previous rhythm abnormalities were recorded.
      CONCLUSIONS: This study corroborates the hypothesis that right hemispheric
      hematomas induce supraventricular arrhythmias more frequently. The possible
      association between severe ventricular arrhythmias and sudden death with left
      hemisferic hematomas should be studied in a higher number of patients. We
      recommend monitoring every acute case of intracerebral hematoma when possible.

PMID- 9634673
TI  - [Autonomic and metabolic sequelae of global and focal cerebral ischemia in an
      experimental model].
AB  - INTRODUCTION: During the last decades the influence of cerebrovascular disease on
      heart and autonomic nervous system has been studied in numerous reports.
      Autonomic and metabolic changes have been described during brain ischemia.
      METHODS: We studied some parameters and its modifications during global (GBI) and
      focal brain ischemia (FBI). Ten Wistar rats were subjected to global ischemia and
      eleven to focal brain ischemia, during 20 and 90 minutes followed in both cases
      by reperfusion. Mean blood pressure, heart rate and glycaemia before, during and
      after brain ischemia were registered. pH, pO2 and pCO2 were maintained within
      normal range using endovenous tamponed solutions. RESULTS: During GBI the blood
      pressure rose and returned to normal in the reperfusion period. Heart rate
      decreased in both stroke models and hyperglycaemia was present from the beginning
      in two groups. CONCLUSIONS: GBI and FBI bring about autonomic changes as
      increased mean blood pressure (only in GBI) and decreased heart rate; probably
      these might be explained by an autonomic nervous system disorder or by
      intracranial hypertension. Hyperglycaemia could be related to cathecholamines
      secretion. These effects might influence in the pathophysiology of brain
      ischemia.

PMID- 9634674
TI  - [Comparison of hypertensive and non-hypertensive lacunar infarcts].
AB  - INTRODUCTION: Arterial hypertension and hypohyalinosis of the arterias
      perforantes are said to be the commonest cause of lacunar infarcts, although
      other etiological factors and anatomo-pathological lesions are described more and
      more frequently. We designed a study to compare the clinical topographic and
      prognostic characteristics of patients with hypertensive and non-hypertensive
      lacunar infarcts. MATERIAL AND METHODS: We selected 51 patients with lacunar
      infarcts: in 23 (45%) arterial hypertension was the only etiological factor
      recognized. In 28 (55%) other risk factors (16 diabetes mellitus, 17 cardiopathy,
      8 hyperlipemia, 13 cigarette smoking and 11 alcoholism) were seen. We evaluated
      the form of presentation, the type of infarct and whether this was associated
      with headache. The degree of defect was determined on admission using the
      Canadian scale. The size of the infarct was measured on CT or RM, using whichever
      measurement was greater. The evolution of the condition was determined on the
      Canadian scale and the index of Barthel after three months. RESULTS: Age and sex
      distribution was similar to both groups. Motor hemiparesia was the commonest
      lacunar syndrome and the distribution was similar. There was no difference in
      form of onset, association with headache or neurological defect between the
      hypertensive and non-hypertensive lacunar infarcts. The topographical
      distribution, the presentation of single or multiple lesions, the size of the
      infarcts and the prognosis were similar in both groups. CONCLUSIONS: Lacunar
      infarcts, whether hypertensive or not, show no differences regarding clinical,
      neuro-radiological or evolutionary characteristics.

PMID- 9634675
TI  - [Magnesium in cerebrospinal fluid in acute cerebral ischemia: its relation to
      glutamate neurotoxicity].
AB  - INTRODUCTION: In animal models it has been shown that there is an increase in
      tissue magnesium concentration during cerebral ischemia. We studied the changes
      in magnesium levels in the cerebrospinal fluid (CSF) during the acute phase of
      cerebral ischemia. MATERIAL AND METHODS: We included 95 patients with first
      ischemic cerebral infarcts admitted to hospital within the first 24 hours and
      also 37 controls. CT scan was done on admission and between four and seven days
      later (when the volume of the infarct was determined). The neurological defect
      was evaluated on the Canadian scale on admission, after 48 hours, on the seventh
      day and after three months. The CSF magnesium concentration was determined using
      a colorimetric method and the glutamate by HPLC. RESULTS: The CSF magnesium
      concentrations were significantly higher in the patients than in the controls
      (2.6 +/- 0.6 mmol/l vs 2.2 +/- 0.6 mmol/l p = 0.0001). The magnesium
      concentration was higher in the larger infarcts (Pearson's coefficient = 0.2901,
      p = 0.0043), and in those presenting greater neurological defects after 48 hours
      (Spearman's coefficient = -0.4649, p < 0.0001). The magnesium concentration was
      not related to the presence of early signs on the initial CT scan and the
      Canadian scale rating on admission. The concentration of magnesium was
      significantly correlated with that of glutamate (Pearson coefficient = 0.7735, p
      < 0.0001). CONCLUSIONS: The levels of magnesium in the CSF were satisfactorily
      related to the volumes of the infarct and the intensity of the neurological
      defect. However, this association was late, occurring more than 48 hours after
      onset of the condition.

PMID- 9634676
TI  - [Supranuclear ophthalmoplegia and walk disorders in an elderly man].

PMID- 9634677
TI  - [Hip hemiplegia and parasagittal mass: different etiologies].

PMID- 9634678
TI  - [Bibliographic references in REVISTA DE NEUROLOGIA in 1997].

PMID- 9634679
TI  - [Evoked motor potentials in the diagnosis of conversion hysteria].

PMID- 9634680
TI  - [Cuban epidemic of optic myeloneuropathy].

PMID- 9634681
TI  - [Choreoathetosis: an uncommon sign of lithium poisoning].

PMID- 9634682
TI  - [The importance of a therapeutic approach to families of children with cognitive
      defects].

PMID- 9634683
TI  - [Disability and multiple sclerosis].

PMID- 9634684
TI  - [Late onset and slow course of Friedreich ataxia. A clinical electrophysiological
      molecular genetic study].

PMID- 9634685
TI  - [Prophylactic treatment with gabapentin in chronic daily headache resistant to
      other drugs].

PMID- 9634686
TI  - [Acute myocardial infarct in Switzerland: results from the PIMICS Heart Infarct
      Register. PIMICS Project (Prospective Ischemia Myocardial Infarction Captopril
      Survey)].
AB  - The aim of the PIMICS project was to create, for the first time in Switzerland, a
      registry of data concerning epidemiology and therapy in patients hospitalised for
      acute myocardial infarction covering all regions of the country. During 1995/96
      73 Swiss hospitals of all categories took part in the PIMICS project. The ratio
      between males and females in the 3877 registered patients was 2.6:1 (2791 men vs.
      1086 women). Female patients were significantly older than males (70.4 +/- 12.0
      years vs. 63.4 +/- 12.6 years; p < 0.0001). The prevalence of risk factors
      differed between men and women: significantly more women had hypertension or
      diabetes, whereas smoking was more prevalent in males. The median delay between
      onset of symptoms and arrival at the hospital was 5.5 hours. Thrombolysis and
      primary angioplasty were more frequently performed in men (40.4% vs. 31.2% in
      women, p < 0.0001, and 5.7% in men vs. 3.5% in women, p = 0.005 respectively).
      During the acute phase males were treated more frequently with betablockers. The
      overall in-hospital mortality was 9.1%. It was significantly higher in female
      patients (13.5% vs. 7.4% in men; p < 0.0001) and in patients with reinfarction
      (14.5% vs. 7.1%; p < 0.0001). The mean hospital stay was 12.6 +/- 5.3 days. Only
      7.7% of all patients with acute myocardial infarction were discharged within 6
      days. At discharge, 51.7% were treated with betablockers and 69.3% with aspirin;
      44.8% received ACE-inhibitors and only 13.8% lipid-lowering drugs. Follow-up
      measures such as coronary angiography and/or angioplasty or bypass surgery were
      performed significantly more often in males (45.0% vs. 32.9%; p < 0.0001).
      Likewise, men were more frequently assigned to a rehabilitation program than
      women (38.2% vs. 32.9%; p = 0.0004). The pre-hospital delay in patients with
      acute myocardial infarction remains too long. Primary and secondary prevention
      should be intensified in high risk groups, particularly in females. Thrombolysis
      and primary angioplasty as mainstays of treatment in acute myocardial infarction
      are generally used too sparingly, especially in women. With such measures the
      hospital stay could be shortened further.

PMID- 9634687
TI  - [Tuberculosis: contact tracing and preventive chemotherapy].
AB  - Tuberculosis is transmitted from patients with lung disease to sensitive
      individuals by inhalation of infectious particles expelled during cough.
      Therefore, the search for infected subjects among relatives of patients with
      infectious tuberculosis is the best method of preventing later development of the
      disease in populations where the prevalence of tuberculosis is low. Contact
      tracing relies on the tuberculin skin test, followed by chest X-ray if indicated
      and bacteriological examination of sputum. In recently infected subjects,
      particularly the young, preventive chemotherapy has been shown to decrease the
      risk of later disease.

PMID- 9634688
TI  - [Diagnostic approach to pulmonary embolism].
AB  - Despite its relatively high frequency, pulmonary embolism remains difficult to
      diagnose due to its non-specific symptomatology and the diagnostic uncertainties
      of the paraclinical tests used. The diagnostic approach is based initially on
      evaluation of the a priori clinical probability of thromboembolic disease, then
      on a decisional strategy regarding the choice of the most efficient paraclinical
      tests. The specific characteristics of the paraclinical tests are reviewed. A
      series of decisional algorithms is proposed based on the notion that pulmonary
      embolism and deep-vein thrombosis are two facets of the same disease. In the
      majority of cases, performing invasive tests such as pulmonary angiography and
      phlebography of the legs become less necessary with the use of the proposed
      strategies, which serve to identify the patients to be treated as well as those
      who do not require anticoagulant therapy.

PMID- 9634689
TI  - [Physician's attitude to acute non-cardiac thoracic pain].
AB  - Acute non-cardiac chest pain is very commonly reported in ambulatory care or
      hospitalized patients. Most cases arise from non-organic causes and should be
      treated by the primary care physician after having reasonably excluded curable or
      potentially life-threatening diseases. This new approach is designed to save
      costly and unnecessary investigations and more effectively assist patients
      suffering from acute non-cardiac chest pain due to anxiety disorders.

PMID- 9634690
TI  - [Solitary fibrous tumor of the pleura with signs of malignancy].

PMID- 9634691
TI  - Structural principles in cell-cycle control: beyond the CDKs.
AB  - Retinoblastoma protein (Rb) interacts with cyclin-dependent kinases and regulates
      the transcription of genes necessary for progression through the S phase of the
      cell cycle. Clues to the atomic mechanisms involved are offered by the structure
      of the two pocket regions of Rb in complex with a short peptide from a viral
      oncoprotein. Structures of cyclins, Rb and TFIIB reveal that a common motif
      occurs in proteins regulating three consecutive events of cell-cycle control.

PMID- 9634692
TI  - Teaching a new dog old tricks?
AB  - The recently determined crystal structures of fragments of the human and vaccinia
      virus type IB topoisomerases reveal unexpected similarity with the lambda family
      of site-specific recombinases. The conservation of structure suggests a common
      mechanism, indicating that topoisomerase activity may be the consequence of
      uncoupling DNA strand cleavage/religation from synapsis.

PMID- 9634693
TI  - Transcriptional cooperativity: bending over backwards and doing the flip.
AB  - The structures of the NFAT1-Fos-Jun-ARRE2 and MAT alpha 2-MCM1-STE6 transcription
      regulatory complexes reveal changes in protein conformation and DNA bending.
      Studies of the interaction between Fos-Jun and NFAT1 in solution corroborate the
      crystallographic analysis. These results manifest the flexibility required for
      cooperative binding to composite regulatory elements.

PMID- 9634694
TI  - High-resolution structure of an archaeal zinc ribbon defines a general
      architectural motif in eukaryotic RNA polymerases.
AB  - BACKGROUND: Transcriptional initiation and elongation provide control points in
      gene expression. Eukaryotic RNA polymerase II subunit 9 (RPB9) regulates start
      site selection and elongational arrest. RPB9 contains Cys4 Zn(2+)-binding motifs
      which are conserved in archaea and homologous to those of the general
      transcription factors TFIIB and TFIIS. RESULTS: The structure of an RPB9 domain
      from the hyperthermophilic archaeon Thermococcus celer was determined at high
      resolution by NMR spectroscopy. The structure consists of an apical tetrahedral
      Zn(2+)-binding site, central beta sheet and disordered loop. Although the
      structure lacks a globular hydrophobic core, the two surfaces of the beta sheet
      each contain well ordered aromatic rings engaged in serial edge-to-face
      interactions. Basic sidechains are clustered near the Zn(2+)-binding site. The
      disordered loop contains sidechains conserved in TFIIS, including acidic residues
      essential for the stimulation of transcriptional elongation. CONCLUSIONS: The
      planar architecture of the RPB9 zinc ribbon-distinct from that of a conventional
      globular domain-can accommodate significant differences in the alignment of
      polar, non-polar and charged sidechains. Such divergence is associated with local
      and non-local changes in structure. The RPB9 structure is distinguished by a
      fourth beta strand (extending the central beta sheet) in a well ordered N
      terminal segment and also differs from TFIIS (but not TFIIB) in the orientation
      of its apical Zn(2+)-binding site. Cys4 Zn(2+)-binding sites with distinct
      patterns of polar, non-polar and charged residues are conserved among unrelated
      RNAP subunits and predicted to form variant zinc ribbons.

PMID- 9634695
TI  - Structure of an aromatic-ring-hydroxylating dioxygenase-naphthalene 1,2
      dioxygenase.
AB  - BACKGROUND: Pseudomonas sp. NCIB 9816-4 utilizes a multicomponent enzyme system
      to oxidize naphthalene to (+)-cis-(1R,2S)-dihydroxy-1,2-dihydronaphthalene. The
      enzyme component catalyzing this reaction, naphthalene 1,2-dioxygenase (NDO),
      belongs to a family of aromatic-ring-hydroxylating dioxygenases that oxidize
      aromatic hydrocarbons and related compounds to cis-arene diols. These enzymes
      utilize a mononuclear non-heme iron center to catalyze the addition of dioxygen
      to their respective substrates. The present study was conducted to provide
      essential structural information necessary for elucidating the mechanism of
      action of NDO. RESULTS: The three-dimensional structure of NDO has been
      determined at 2.25 A resolution. The molecule is an alpha 3 beta 3 hexamer. The
      alpha subunit has a beta-sheet domain that contains a Rieske [2Fe-2S] center and
      a catalytic domain that has a novel fold dominated by an antiparallel nine
      stranded beta-pleated sheet against which helices pack. The active site contains
      a non-heme ferrous ion coordinated by His208, His213, Asp362 (bidentate) and a
      water molecule. Asn201 is positioned further away, 3.75 A, at the missing axial
      position of an octahedron. In the Rieske [2Fe-2S] center, one iron is coordinated
      by Cys81 and Cys101 and the other by His83 and His104. CONCLUSIONS: The domain
      structure and iron coordination of the Rieske domain is very similar to that of
      the cytochrome bc1 domain. The active-site iron center of one of the alpha
      subunits is directly connected by hydrogen bonds through a single amino acid,
      Asp205, to the Rieske [2Fe-2S] center in a neighboring alpha subunit. This is
      likely to be the main route for electron transfer.

PMID- 9634696
TI  - Characterizing global substates of myoglobin.
AB  - BACKGROUND: The massive amount of information generated from current molecular
      dynamics simulations makes the data difficult to analyze efficiently. Principal
      component analysis has been used for almost a century to detect and characterize
      data relationships and to reduce the dimensionality for problems in many fields.
      Here, we present an adaptation of principal component analysis using a partial
      singular value decomposition (SVD) for investigating both the localized and
      global motions of macromolecules. RESULTS: Configuration space projections from
      the SVD analysis of a variety of myoglobin simulations are used to characterize
      the dynamics of the protein. This technique reveals new dynamical motifs, which
      quantify proposed hierarchical structures of conformational substates for
      proteins and provide a means by which configuration space sampling efficiency may
      be probed. The SVD clearly shows that solvent effects facilitate transitions
      between global conformational substates for myoglobin molecular dynamics
      simulations. Lyapunov exponents calculated from the configuration space
      divergence of 15 trajectories agree with previous predictions for the chaotic
      behavior of complex protein systems. CONCLUSIONS: Configuration space projections
      provide invaluable information about protein motions that would be extremely
      difficult to obtain otherwise. While the configuration space for myoglobin is
      quite large, it does have structure. Our analysis of this structure shows that
      the protein hops between a number of distinct global conformational states, much
      like the local behavior observed for an individual residue.

PMID- 9634697
TI  - Crystal structure of the receptor-binding domain of alpha 2-macroglobulin.
AB  - BACKGROUND: The large plasma proteinase inhibitors of the alpha 2-macroglobulin
      superfamily inhibit proteinases by capturing them within a central cavity of the
      inhibitor molecule. After reaction with the proteinase, the alpha-macroglobulin
      proteinase complex binds to the alpha-macroglobulin receptor, present in the
      liver and other tissues, and becomes endocytosed and rapidly removed from the
      circulation. The complex binds to the receptor via recognition sites located on a
      separate domain of approximately 138 residues positioned at the C terminus of the
      alpha-macroglobulin subunit. RESULTS: The crystal structure of the receptor
      binding domain of bovine alpha 2-macroglobulin (bRBD) has been determined at a
      resolution of 1.9 A. The domain primarily comprises a nine-strand beta structure
      with a jelly-roll topology, but also contains two small alpha helices.
      CONCLUSIONS: The surface patch responsible for receptor recognition is thought to
      involve residues located on one of the two alpha helices of the bRBD as well as
      residues in two of the beta strands. Located on this alpha helix are two lysine
      residues that are important for receptor binding. The structure of bRBD is very
      similar to the approximately 100-residue C-terminal domain of factor XIII, a
      transglutaminase from the blood coagulation system.

PMID- 9634698
TI  - The crystal structure of phenol hydroxylase in complex with FAD and phenol
      provides evidence for a concerted conformational change in the enzyme and its
      cofactor during catalysis.
AB  - BACKGROUND: The synthesis of phenolic compounds as by-products of industrial
      reactions poses a serious threat to the environment. Understanding the enzymatic
      reactions involved in the degradation and detoxification of these compounds is
      therefore of much interest. Soil-living yeasts use flavin adenine dinucleotide
      (FAD)-containing enzymes to hydroxylate phenols. This reaction initiates a
      metabolic sequence permitting utilisation of the aromatic compound as a source of
      carbon and energy. The phenol hydroxylase from Trichosporon cutaneum hydroxylates
      phenol to catechol. Phenol is the best substrate, but the enzyme also accepts
      simple hydroxyl-, amino-, halogen- or methyl-substituted phenols. RESULTS: The
      crystal structure of phenol hydroxylase in complex with FAD and phenol has been
      determined at 2.4 A resolution. The structure was solved by the MIRAS method. The
      protein model consists of two homodimers. The subunit consists of three domains,
      the first of which contains a beta sheet that binds FAD with a typical beta alpha
      beta nucleotide-binding motif and also a fingerprint motif for NADPH binding. The
      active site is located at the interface between the first and second domains; the
      second domain also binds the phenolic substrate. The third domain contains a
      thioredoxin-like fold and is involved in dimer contacts. The subunits within the
      dimer show substantial differences in structure and in FAD conformation. This
      conformational flexibility allows the substrate to gain access to the active site
      and excludes solvent during the hydroxylation reaction. CONCLUSIONS: Two of the
      domains of phenol hydroxylase are similar in structure to p-hydroxybenzoate
      hydroxylase. Thus, phenol hydroxylase is a member of a family of flavin
      containing aromatic hydroxylases that share the same overall fold, in spite of
      large differences in amino acid sequences and chain length. The structure of
      phenol hydroxylase is consistent with a hydroxyl transfer mechanism via a peroxo
      FAD intermediate. We propose that a movement of FAD takes place in concert with a
      large conformational change of residues 170-210 during catalysis.

PMID- 9634699
TI  - The structural basis of ankyrin-like repeat function as revealed by the solution
      structure of myotrophin.
AB  - BACKGROUND: Myotrophin is a 12.5 kDa protein that appears to have a key role in
      the initiation of cardiac hypertrophy, a central process in many heart diseases.
      Myotrophin primarily comprises ankyrin-like (ANK) repeats, the 33 amino acid
      motifs involved in a wide range of protein-protein interactions. As a first step
      in the structure-based search for cardiac hypertrophy antagonists and in order to
      gain insight into the molecular basis of action of the ubiquitous and
      multifunctional ANK repeat motif, we have determined the solution structure of
      myotrophin using multidimensional heteronuclear NMR spectroscopy. RESULTS: The
      myotrophin structure determination was based on 2786 experimental NMR restraints,
      and the precision of the coordinates for the final 45 simulated-annealing
      structures is 0.43 A for the backbone atoms and 0.87 A for all atoms. The
      structure of myotrophin is well defined and is ellipsoidal: approximately 46 A
      long and 21 A wide. The ANK repeats, which constitute the main part of the
      myotrophin structure, are characteristic of a hairpin-like protruding tip
      followed by a helix-turn-helix motif. The V-shaped helix-turn-helix of the ANK
      repeats stack sequentially in bundles and are stabilized by compact hydrophobic
      cores, whereas the protruding tips are less ordered. This arrangement is quite
      different to the continuous beta-sheet topology observed in the corresponding
      regions of another ANK protein, 53BP2, the structure of which was determined in
      complex with p53. CONCLUSIONS: The solution structure of myotrophin provides
      important insights into the structural and dynamic features of the ANK motif, and
      suggests that the protruding tips with highly variable sequences may be critical
      to facilitate diverse protein-protein recognition. The present structure also
      provides a molecular basis for the further functional characterization of
      myotrophin and the development of therapeutics for hypertrophy-related heart
      diseases.

PMID- 9634700
TI  - Interfering with the inhibitory mechanism of serpins: crystal structure of a
      complex formed between cleaved plasminogen activator inhibitor type 1 and a
      reactive-centre loop peptide.
AB  - BACKGROUND: Plasminogen activator inhibitor type 1 (PAI-1) is an important
      endogenous regulator of the fibrinolytic system. Reduction of PAI-1 activity has
      been shown to enhance dissolution of blood clots. Like other serpins, PAI-1 binds
      covalently to a target serine protease, thereby irreversibly inactivating the
      enzyme. During this process the exposed reactive-centre loop of PAI-1 is believed
      to undergo a conformational change becoming inserted into beta sheet A of the
      serpin. Incubation with peptides from the reactive-centre loop transform serpins
      into a substrate for their target protease. It has been hypothesised that these
      peptides bind to beta sheet A, thereby hindering the conformational rearrangement
      leading to loop insertion and formation of the stable serpin-protease complex.
      RESULTS: We report here the 1.95 A X-ray crystal structure of a complex of a
      glycosylated mutant of PAI-1, PAI-1-ala335Glu, with two molecules of the
      inhibitory reactive-centre loop peptide N-Ac-TVASS-NH2. Both bound peptide
      molecules are located between beta strands 3A and 5A of the serpin. The binding
      kinetics of the peptide inhibitor to immobilised PAI-1-Ala335Glu, as monitored by
      surface plasmon resonance, is consistent with there being two different binding
      sites. CONCLUSIONS: This is the first reported crystal structure of a complex
      formed between a serpin and a serpin inhibitor. The localisation of the
      inhibitory peptide in the complex strongly supports the theory that molecules
      binding in the space between beta strands 3A and 5A of a serpin are able to
      prevent insertion of the reactive-centre loop into beta sheet A, thereby
      abolishing the ability of the serpin to irreversibly inactivate its target
      enzyme. The characterisation of the two binding sites for the peptide inhibitor
      provides a solid foundation for computer-aided design of novel, low molecular
      weight PAI-1 inhibitors.

PMID- 9634701
TI  - Solution structure of the heparin-binding domain of vascular endothelial growth
      factor.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is an endothelial cell
      specific mitogen and is a potent angiogenic and vascular permeabilizing factor.
      VEGF is also an important mediator of pathological angiogenesis associated with
      cancer, rheumatoid arthritis and proliferative retinopathy. The binding of VEGF
      to its two known receptors, KDR and Flt-1, is modulated by cell-surface
      associated heparin-like glycosaminoglycans and exogenous heparin or heparan
      sulfate. Heparin binding to VEGF165, the most abundantly expressed isoform of
      VEGF, has been localized to the carboxy-terminal 55 residues; plasmin cleavage of
      VEGF165 yields a homodimeric 110-residue amino-terminal receptor-binding domain
      (VEGF110) and two 55-residue carboxy-terminal heparin-binding fragments. The
      endothelial cell mitogenic potency of VEGF110 is decreased significantly relative
      to VEGF165, indicating that the heparin-binding domains are critical for
      stimulating endothelial cell proliferation. RESULTS: The solution structure of
      the 55-residue heparin-binding domain of VEGF165 has been solved using data from
      two-dimensional homonuclear and three-dimensional heteronuclear NMR spectroscopy.
      The structure has two subdomains, each containing two disulfide bridges and a
      short two-stranded antiparallel beta sheet; the carboxy-terminal subdomain also
      contains a short alpha helix. Hydrophobic interactions are limited to sidechains
      packing against the disulfide bridges. CONCLUSIONS: The heparin-binding domain of
      VEGF has no significant sequence or structural similarity to any known proteins
      and thus represents a novel heparin-binding domain. Most of the positively
      charged amino acid sidechains are localized on one side of the carboxy-terminal
      subdomain or on an adjacent disordered loop in the amino-terminal subdomain. The
      observed distribution of surface charges suggests that these residues constitute
      a heparin interaction site.

PMID- 9634702
TI  - Barley alpha-amylase bound to its endogenous protein inhibitor BASI: crystal
      structure of the complex at 1.9 A resolution.
AB  - BACKGROUND: Barley alpha-amylase is a 45 kDa enzyme which is involved in starch
      degradation during barley seed germination. The released sugars provide the plant
      embryo with energy for growth. The major barley alpha-amylase isozyme (AMY2)
      binds with high affinity to the endogenous inhibitor BASI (barley alpha
      amylase/subtilisin inhibitor) whereas the minor isozyme (AMY1) is not inhibited.
      BASI is a 19.6 kDa bifunctional protein that can simultaneously inhibit AMY2 and
      serine proteases of the subtilisin family. This inhibitor may therefore prevent
      degradation of the endosperm starch during premature sprouting and protect the
      seed from attack by pathogens secreting proteases. RESULTS: The crystal structure
      of AMY2 in complex with BASI was determined and refined at 1.9 A resolution. BASI
      consists of a 12-stranded beta-barrel structure which belongs to the beta-trefoil
      fold family and inhibits AMY2 by sterically occluding access of the substrate to
      the active site of the enzyme. The AMY2-BASI complex is characterized by an
      unusual completely solvated calcium ion located at the protein-protein interface.
      CONCLUSIONS: The AMY2-BASI complex represents the first reported structure of an
      endogenous protein-protein complex from a higher plant. The structure of the
      complex throws light on the strict specificity of BASI for AMY2, and shows that
      domain B of AMY2 contributes greatly to the specificity of enzyme-inhibitor
      recognition. In contrast to the three-dimensional structures of porcine
      pancreatic alpha-amylase in complex with proteinaceous inhibitors, the AMY2-BASI
      structure reveals that the catalytically essential amino acid residues of the
      enzyme are not directly bound to the inhibitor. Binding of BASI to AMY2 creates a
      cavity, exposed to the external medium, that is ideally shaped to accommodate an
      extra calcium ion. This feature may contribute to the inhibitory effect, as the
      key amino acid sidechains of the active site are in direct contact with water
      molecules which are in turn ligated to the calcium ion.

PMID- 9634704
TI  - Tonsillar biopsy and PrPSc detection in the preclinical diagnosis of scrapie.
AB  - Preliminary findings have indicated that in naturally infected sheep, fully
      susceptible to scrapie (VRQ-homozygous), PrPSc can be detected in the tonsils
      approximately one year before the expected onset of clinical disease, whereas no
      immunostaining can be detected in animals with a semi-resistant genotype. This
      paper describes the technique for taking tonsillar biopsies from sheep and gives
      the results of the completed experiment. In another experiment PrPSc was detected
      even earlier in comparable VRQ-homozygous sheep born and raised in different
      surroundings. At three-and-a-half months of age no PrPSc could be detected in
      three homozygous susceptible sheep (VRQ/VRQ), but PrPSc was detected at four
      months in one similar sheep. At eight months of age all seven sampled VRQ/VRQ
      sheep showed positive immunostaining in the biopsies, but none of the biopsies
      from three VRQ/ARQ heterozygotes showed any immunostaining; they were positive
      when sampled at 14 to 15 months of age. Biopsies from VRQ/ARR sheep were negative
      throughout this period. On the basis of the established or expected incubation
      period, PrPSc could thus be detected in the tonsils of live susceptible animals
      at between one-third and a half of the incubation period, more than one-and-a
      half years before clinical signs normally appear in both these genotypes.

PMID- 9634703
TI  - Co-crystal structure of sterol regulatory element binding protein 1a at 2.3 A
      resolution.
AB  - BACKGROUND: The sterol regulatory element binding proteins (SREBPs) are helix
      loop-helix transcriptional activators that control expression of genes encoding
      proteins essential for cholesterol biosynthesis/uptake and fatty acid
      biosynthesis. Unlike helix-loop-helix proteins that recognize symmetric E-boxes
      (5'-CANNTG-3'), the SREBPs have a tyrosine instead of a conserved arginine in
      their basic regions. This difference allows recognition of an asymmetric sterol
      regulatory element (StRE, 5'-ATCACCCAC-3'). RESULTS: The 2.3 A resolution co
      crystal structure of the DNA-binding portion of SREBP-1a bound to an StRE reveals
      a quasi-symmetric homodimer with an asymmetric DNA-protein interface. One monomer
      binds the E-box half site of the StRE (5'-ATCAC-3') using sidechain-base contacts
      typical of other helix-loop-helix proteins. The non-E-box half site (5'-GTGGG-3')
      is recognized through entirely different protein-DNA contacts. CONCLUSIONS:
      Although the SREBPs are structurally similar to the E-box-binding helix-loop
      helix proteins, the Arg-->Tyr substitution yields dramatically different DNA
      binding properties that explain how they recognize StREs and regulate expression
      of genes important for membrane biosynthesis.

PMID- 9634705
TI  - Attempted elimination of porcine reproductive and respiratory syndrome virus from
      a seedstock farm by vaccination of the breeding herd and nursery depopulation.
AB  - An attempt was made to eliminate the virus of porcine reproductive and
      respiratory syndrome from a seedstock farm by using the combined strategies of
      vaccination and nursery depopulation. The breeding herd was vaccinated with a
      modified-live virus vaccine; all breeding and lactating adult animals were
      vaccinated twice, with a 30-day interval between vaccinations. All the sows were
      vaccinated in this way except for those in the third trimester of gestation (66
      to 114 days) which were vaccinated on day 7 of lactation and 30 days later. A
      serological profiling system was developed to assess when the piglets became
      infected. Pigs from vaccinated sows were profiled at weekly intervals after
      weaning, using immunofluorescence tests for the detection of IgM and IgG, a serum
      neutralising antibody test, and virus isolation. After completion of the
      protocol, the nursery and finishing sites were monitored for 15 months. Evidence
      of reinfection in the finishing stage was detected 16 months after depopulation,
      but not in the nursery or the breeding herd. The source of the virus was not
      determined, but suspected origins included a lack of biosecurity, aerosol
      transmission from another infected farm or a persistently infected pig.

PMID- 9634706
TI  - Assessment of the modified Forssell's procedure for the treatment of oral
      stereotypies in 10 horses.
AB  - The modified Forssell's procedure was performed on 10 horses in an attempt to
      cure oral stereotypies. Three horses were cured completely, two horses were
      considerably improved, and five horses continued to perform the stereotypy after
      periods of remission ranging from two weeks to six months. This rate of success
      for the modified Forssell's procedure, as in other published reports, was lower
      than for the original Forssell's procedure. Surgery to eliminate a stereotypical
      behaviour pattern may exacerbate the stress for an animal and the modified
      Forssell's procedure can no longer be recommended for the treatment of oral
      stereotypies in horses.

PMID- 9634707
TI  - Comparison of three treatments for bovine endometritis.
AB  - Three commercial preparations for the treatment of bovine endometritis were
      compared: an intrauterine infusion of 1500 mg oxtytetracycline hydrochloride
      solution, an intramuscular injection of 500 micrograms cloprostenol (a synthetic
      analogue of prostaglandin F2 alpha), and an intramuscular injection of 3 mg
      oestradiol benzoate/500 kg estimated bodyweight. A total of 300 cases of
      endometritis were treated, of which 225 involved first, 67 involved second, and
      eight involved third or subsequent treatments. The overall success rate of
      treatment was 68 per cent. Oxytetracycline was successful in 73 per cent of
      cases, cloprostenol in 67 per cent and oestradiol in 63 per cent of cases. There
      was no significant difference between the success rates of the treatments, except
      for cows with mild endometritis in which oxytetracycline was more successful than
      oestradol (86 v 66 per cent, P < 0.05). Mild cases were treated more successfully
      than moderate cases (78 v 61 per cent, P < 0.01), and more successfully than
      severe cases (78 v 44 per cent, P < 0.001). Prostaglandin F2 alpha was more
      successful if the milk progesterone concentration was > 7 ng/ml at the time of
      treatment (P < 0.05). The presence of a smelly discharge at the time of treatment
      reduced the success rate by 17 per cent (P < 0.02). The treatment to conception
      interval for all successful treatments of endometritis by prostaglandin F2 alpha
      was 18.1 days shorter than for oestradiol (68.3 v 86.4 days, P < 0.02), and the
      interval for oxytetracycline was 16.2 days shorter than for oestradiol (70.2 v
      86.4 days, P < 0.05).

PMID- 9634708
TI  - Maternal transmission of BSE: interpretation of the data on the offspring of BSE
      affected pedigree suckler cows.

PMID- 9634709
TI  - Bronchobiliary fistula in two adult cattle.

PMID- 9634710
TI  - Uterine drainage under general anaesthesia before ovariohysterectomy in two
      mares.

PMID- 9634711
TI  - Funding veterinary education.

PMID- 9634712
TI  - Use of clomipramine for separation anxiety in dogs.

PMID- 9634713
TI  - Conformation defects in draught donkeys.

PMID- 9634714
TI  - [Potentially dangerous photosensitizers among drugs and medicinal plant
      extracts].
AB  - The review deals with photosensitizing properties of drugs and plant extracts.
      Some compounds are able to cause side effects such as phototoxicity and
      photoallergy. Revealing and study of harmful photosensitizers is actual problem
      in connection with changing photoecological situation.

PMID- 9634716
TI  - [Effect of prenatal gamma-irradiation on functional properties of rat liver
      adenylate cyclase].
AB  - In the present work the effects of long-term prenatal gamma-irradiation (0.5 Gy)
      on the glucagon signalling through adenylyl cyclase have been investigated. In
      utero gamma-irradiation resulted in the increase of basal and GTP-stimulated
      adenylyl cyclase activity, whereas, the adenylyl cyclase response to glucagon was
      essentially reduced. The comparison of kinetic constants estimated from dose
      response data for GTP and glucagon suggests that prenatal chronic irradiation
      prompted (i) the decrease in rate of GTP hydrolysis on Gs-protein; (ii) the
      reduction of glucagon potency to accelerate the exchange GDP for GTP on Gs
      protein.

PMID- 9634715
TI  - [Sulfated polysaccharides as inhibitors of receptor activity of P-selectin and P
      selectin-dependent inflammation].
AB  - The inhibitory effects of sulfated polysaccharides-fucoidan and heparin on P
      selectin-ligand interaction in vitro and on the ability of fucoidan to inhibit
      the leukocyte extravasation in rat peritonitis were studied. The lectin activity
      of P-selectin in vitro was based on its ability to bind lectin-labeled synthetic
      ligand, Sialyl-Lea/x, conjugated with polyacrylamide (PAA). Fucoidan and heparin
      inhibited binding of labeled ligand to both purified P-selectin and the activated
      platelets expressing P-selectin on their surface. The inhibitory effect of
      fucoidan 100-fold higher than that of heparin. As P-selectin plays an important
      role at an earlier stage of the inflammation process, the antiinflammatory action
      of fucoidan on P-selectin-dependent peritonitis in rats was studied. Peritonitis
      was induced by intraperitoneal injection of the peptone solution and was
      characterized by an increase in total cell number and neutrophil percentage in
      rat peritone exudate. Intravenous injection of fucoidan was found to cause a dose
      and time-dependent reduction of neutrophil extravasation into inflamed
      peritoneum. The minimal dose of fucoidan, that was able to produce 96.8 +/- 2.9%
      inhibition of neutrophil extravasation--if administered within the first 15 min
      after peptone-B was 0.8 mg per rat. Significant effect of fucoidan injection
      (about 80% inhibition) was also obtained 1.5 h after the induction of
      inflammation. Fucoidan administered 2.5 h after peptone had virtually no effect
      on neutrophil extravasation. The data obtained show that fucoidan blocks the
      inflammation process at its earlier stages--most probably at the expense of its
      interaction with P-selectin.

PMID- 9634717
TI  - [Dual reciprocal regulation of the succinate oxidation system in heart and liver
      mitochondria in pathological conditions].
AB  - The phenomenon of the dual reciprocal regulation of succinate dependent 2H+/Ca2+
      exchange was studied in heart and liver mitochondria of experimental animals
      (allogenic heart transplantation in rat; myocardium infarction in rabbits;
      pulmonary arteria coarctation in dogs) and in liver bioptates from patients with
      stomach ulcer. Under pathology two coupled but opposite changes (simultaneous
      activation and inhibition) in succinate dependent Ca2+ transport occur. The
      inhibition of Ca2+ transport was detected by its elimination with glutamate,
      being mostly pronounced after cycle of ADP phosphorylation added to suspension of
      mitochondria. The treatment of animal with 2-oxoglutarate abolished this
      inhibition. This was not observed in healthy animals. The described phenomenon
      can prevent hyperactivation of succinate oxidation under strong pathological
      (distress) influences.

PMID- 9634718
TI  - [Accumulation of vitamin E in dimethylnitrosamine-induced kidney tumors in rats
      with various levels of alpha-tocopherol supplementation].
AB  - The effect of a long-lasting loading with alpha-tocopherol on the development of
      dimethylnitrosamine-induced kidney tumors was investigated in 55 non-bred white
      male rats. The carcinogen was repeatedly introduced into the stomach by means of
      a gastric tube. Starting 24 days after the last administration of the carcinogen
      the alpha-tocopherol loading began and lasted up to the end of the experiment. 21
      rats were loaded with vitamin E introduced into the stomach, 5 times a week at a
      dose of 70 mg/kg body weight. 17 rats received sunflower seed oil--the vitamin E
      solvent; other 17 rats received only standard ration. The control group (20 rats)
      were not treated with the carcinogen. One part of these rats received alpha
      tocopherol by the above schedule while another part--sunflower oil alone. It was
      shown that the alpha-tocopherol loading had no effect on the incidence of renal
      tumors. Nevertheless it enhanced to some extent the rate of their development as
      well as the incidence of blastomes in other organs. Based on histological
      examination, tumors developed in kidneys were of epithelial and mesenchymal
      origins with the mesenchymal tumors occurring more frequently (63-69% of the
      total). Vitamin E content in tumor tissue of rats, loaded or not loaded with
      alpha-tocopherol, was much higher than that in intact kidneys of corresponding
      control animals, suggesting a high tumor tropism of this vitamin. Total lipid
      concentration of tumor tissue was 1.5 times lower than that of intact kidneys.
      Histological nature of tumors had no visible effect on their vitamin E and total
      lipid content.

PMID- 9634719
TI  - [Dynamics of accumulation of CYP2B mRNA in the liver of rats from various strains
      during induction with xenobiotics].
AB  - The transcription level of CYP2B1/2 gene in the liver of Sprague-Dawley (SD),
      Brattleboro (BL) and Wistar (W) rats treated with isosafrol (IS), Arochlor 1254
      (AC), phenobarbital (PB) and triphenildioxane (TPD) was studied. The quantity of
      CYP2B1/2 mRNA was assessed by dot-blot analysis at 18, 48 and 72 hours after
      inducers administration. The mRNA level in SD and BL rats treated with PB reached
      its maximum by 18 hours followed by fast decline. For W strain the amount of mRNA
      reached maximum by 48 hours after treatment. After TPD treatment this parameter
      for SD, W rats reached maximum by 18 hours, while for BL-72 hours. No differences
      in the mRNA amount in rats treated with IS and AC were detected. We are not aware
      of any other data concerning the dynamics of CYP2B1/2 mRNA accumulation during IS
      induction. We showed that in this case a maximum of mRNA was reached by 18 hours.
      Thus, we revealed inducer- and strain-dependent of differences in mRNA
      accumulation dynamics.

PMID- 9634720
TI  - [Determination of a Candida albicans antigen using an amperometric immunoenzyme
      sensor].
AB  - Determination new variant enzyme immunoassay with amperometric enzyme
      immunosensor, including the immobilizing enzyme-choline esterase and antibodies
      against Candida albicans (CA) in biosensitivity part of sensor, for diagnose
      disease of CA. The method for determination of CA based on combination
      immunochemical reactions and voltammetric indication of analytical signal was
      developed. Amperometric enzyme immunosensor developed has been used as detector.
      Differences dilutions of antibody (Ab) against antigen (Ag) of CA immobilizing in
      common with choline esterase (CE). The method of immobilization developed allows
      to receive the sensor with including the immobilized CE and Ab in common. The
      method of determination of CA based on combination the reaction of forming immune
      complex tAb-AgI with enzyme immunosensor for its detection. The dynamic range of
      concentrations determined of Ag depends on degree of dilution of Ab used for
      manufactory biosensitivity part of sensor. The data indicate that the [Ab-Ag]
      immune complexes are stable. This is also confirmed by the values of [Ab-Ag]
      binding constants, obtained in Scatchard coordinates. This method of
      determination doesn't require special preparation of a sample. Selectivity,
      sensitivity, simplicity and quickness are characterize of this method which could
      be used for manufacturing test-sistem for determination CA in blood.

PMID- 9634721
TI  - [Classification of drugs by biochemical mechanism of action].
AB  - Biochemical drugs classification is proposed. Drugs are divided into 6 classes,
      according to their action on: 1) signal-transduction systems, 2) other components
      of plasmatic membranes, 3) intracellularly, 4) gene therapy, 5) extracellularly,
      6) invasive agents. Concrete biochemical mechanisms of action of every class
      drugs are considered and described.

PMID- 9634722
TI  - [Quantitative dependence of structure-antiseizure activity in a series of
      macrocyclic compounds].
AB  - In the present study we have further examined the influence of some structure
      parameters of macrocyclic polyethers upon their anticonvulsant activity in order
      to determine basic pharmacophore fragments. The anticonvulsant activity was
      studied experimentally for 25 new macrocyclic compounds, and their structure,
      physico-chemical properties, electron donor factors and atom charges were
      calculated using programs HyperChem-ChemPlus and HYBOT. The data about atomic
      properties were presented as a set functions of inter-atomic distances (Program
      MOLTRA). The cluster analysis revealed that studied compounds represent two
      independent groups which differ from chemical and pharmacological viewpoints. For
      first group, we have found that anticonvulsant activity of macrocycles is
      determined by their polarizability and spatial orientation of electron donor
      atoms. For another cluster the correlation was found between activity and spatial
      orientation of two hydrophobic fragments and electron donor atoms as well.

PMID- 9634723
TI  - [Solid-phase immunoenzyme analysis of chloramphenicol in human blood serum].
AB  - The method of enzyme linked immunosorbent assay (ELISA) for quantitative
      detection of chloramphenicol (CAP) in human blood serum was developed.
      Peculiarities of the adsorption on the microtitre plates surface of CAP-ovalbumin
      conjugate were investigated. Different conditions of competition stage of the
      analysis were studied. Conditions providing CAP monitoring in human blood serum
      in the clinical range were optimized. Matrix effect on the assay results was
      studied. The specificity of the analytical system was investigated and the
      reagents stability was examined. The method developed permits CAP concentration
      to be determined in human blood serum, diluted 1/100, in the linear range from 10
      to 1000 ng/ml. The assay is characterized by high sensitivity (1 ng/mL) and good
      reproducibility (CV < 12%), assay time is about 3 hours.

PMID- 9634724
TI  - [Possible participation of angiotensin-converting enzyme and leukocyte elastase
      in the pathogenesis of insulin-independent diabetes mellitus].
AB  - It is commonly accepted that the tolerance to insulin and hyperglycemia of the
      patients with non-insulin dependent diabetes mellitus (NIDDM) is due to some
      defect of insulin receptors or disturbances in the signaling pathway of the cell.
      This disease is often accompanied by hypertension. In this paper the high
      activity of plasma kallikrein-kinin system (KKS) (kallikrein activity was 6-8
      times higher than normal), of angiotensin-converting enzyme (ACE) (4 times
      greater than normal), and of leukocyte elastase (2.7 times higher than normal)
      were demonstrated in plasma of patients with NIDDM. Increasing of KKS activity
      was coincident with rising of ACE activity, which may be the cause of the fast
      bradykinin inactivation and arising of hypertension. The treatment with ACE
      inhibitor during 3 months (4 mg of Perindopril per day) decreased ACE activity in
      patients' plasma which was accompanied with decreasing of the arterial pressure
      and some restoration of the carbohydrate metabolism indicators. The
      hyperinsulinemic euglycaemic clamping of 7 patients with NIDDM and essential
      hypertension showed that ACE-inhibitor (Perindopril, 4 mg) prevented bradykinin
      from destruction and increased the glucose consumption by tissues. The high
      activity of polymorphonuclear leukocytes and secretion of the elastase in NIDDM
      patients' plasma and/or instability of plasmatic and granular membranes of
      leukocyte in conditions of hyperglycaemic plasma are probably the cause of
      endothelial irritation and high ACE secretion. Secondly, the leukocyte may be the
      cause of injuring and decreasing of susceptibility of the cell receptors for
      insulin and bradykinin.

PMID- 9634725
TI  - [Relationship of the levels of arachidonic and eicosapentaenoic acid in blood
      serum and low density lipoproteins in patients with bronchial asthma and change
      in the value during restricted-diet therapy].
AB  - Lipid metabolism in patients with infection-dependent bronchial asthma was
      compared before and after 14 days low-diet therapy. After therapy the proportion
      AA/EPA in blood serum and in low density lipoproteins considerably decreased to
      (p < 0.05).

PMID- 9634726
TI  - [The role of neurosurgery in the study of brain-mind relationship].

PMID- 9634727
TI  - [Contemporary trends in the development of psychopharmacotherapy].
AB  - Modern period of psychopharmacology development is characterized by seven main
      features: changes in both clinical picture and course of psychic diseases; the
      use of psychotropic drug in general medicine; some new nosologic entities in ICD
      10 which require of more accurate definition of the methods of therapy; progress
      in the study of biologic mechanisms of psychotropic drugs' action; appearance of
      numerous little-known preparations; discovery of some new aspects in action of
      well-known drugs; increase of the number of patients resistent to
      psychopharmacotherapy. Traditional and original classifications of psychotropic
      drugs are presented. Clinical analysis revealed that clear limits between
      separate groups of drugs are relative. Between the separate classes
      "transitional" drugs exist with distinct properties of both groups. Such drugs
      are thymoneuroleptics, thymotranquilizers, antidepressants with nootropic and
      neuroleptic properties, tranquilonootrops, etc. In accordance with the conception
      of "ideal" drug each class of psychotropic drugs was analyzed in terms of main
      advantages and defects. The advantages of some new drugs are considered.

PMID- 9634728
TI  - [In vivo diagnosis of Creutzfeldt-Jakob disease].
AB  - The paper presents the data concerning usage of some original method of vital
      laboratory diagnostics of Creutzfeldt-Jacob disease that belongs to the group of
      prionic diseases. The method consisted in the inoculation of inoculative culture
      of rat Gasser ganglion's neurinoma by biologic materials investigated (serum and
      clot of blood) with the following passivation and investigation of the
      contaminated culture by means of both morphologic and electron microscopic
      methods. As an example of vital verificated case the wide pathomorphologic
      analysis of the biopsy sample of brain was presented. Besides, the efficiency of
      the investigation of cognitive evoked potentials (P300) together with EEG was
      also demonstrated as the method of objectification of the development of dementia
      in this disease.

PMID- 9634729
TI  - [Clinical regularities in the relapsing and continuing course of phobic
      disorders].
AB  - To evaluate clinical regularities of the development of phobic disorders with
      continuous and recurring course there were examined 67 patients with phobias. The
      duration of disease was from 5 to 50 years. There were 3 variants of relapsing
      and 4 variants of continuous course of phobic disorders taking into consideration
      either presence or absence of the tendency to their progression. In the group of
      relapsing patients 3% of the patients showed no tendency to progression. There
      was also a relapsing variant with a tendency to progression (6.0%). Continuous
      undulating without tendency to progression (8.9%), continuous-undulating with a
      tendency to progression (19.4%), continuous-progressive (25.4%) and stationary
      (28.4%) variants. The authors emphasize that revealed peculiarities in the
      dynamics of phobic disorders with either presence or absence of the tendency to
      progression may help to improve the therapy of such states and to make more
      precise the prognosis of the disease.

PMID- 9634730
TI  - [Psychotic and non-psychotic manifestations of alcoholism in forensic
      psychiatry].
AB  - The paper presents the results of examination of 110 alcoholic patients who have
      committed criminal actions and were recognized as irresponsible at forensic
      examination. It was established that wide spectrum of mental disorders were
      present in such cases--from superacute psychotic states (15 patients) and acute
      disorders (49) to chronic psychoses (33) and encephalopathy (13). According to
      clinical manifestations mental disorders correspond in such cases to reactions of
      exogenic type. In contrast to general medical departments where patients with
      alcoholic delirium prevail, the studied sample of patients had primarily
      psychoses with hallucinative-delirious and delirious disorders. Disorders of
      personality manifested as typical alcoholic, asthenoneurotic, psychopathic-like,
      residual-psychotic, psychoorganic changes and partial dementia (19 cases).

PMID- 9634731
TI  - [Mental disorders in a pediatric clinic].
AB  - In general pediatric clinic 262 children aged 1-15 years with functional
      hyperthermia, functional disorders of cardiac rhythm (extrasystole, paroxysmal
      and recurrent tachycardia), arterial hyper- and hypotension, autonomic
      dysfunctions were examined. 21 children with organic cardiac diseases were
      examined too. Mental disorders were revealed in all the cases: mono- and bipolar
      affective disorders (58.1%) as well as affective-dilutional (10.4%) states,
      primarily in the form of "masked" hypomanias, neurotic and neurotic-like (16.2%),
      psychopathic and psychopathic-like (7.0%), psychoorganic (3.7%) and epileptiform
      (4.6%) syndromes. The spectrum of mental disorders was extremely wide--from
      practical normal (in limits of reactions of personal accentuations or age crisis)
      to endogenic diseases. Combined treatment including drug therapy, psychotherapy
      and family correction was quite effective.

PMID- 9634732
TI  - [Principles of contemporary pharmacotherapy of insomnia].

PMID- 9634733
TI  - [Correlation between functional activity of lymphocytes in patients with
      Alzheimer's dementia and their response to therapy].
AB  - 16 patients with dementia of Alzheimer's type (DAT) were examined. Functional
      activity of lymphocytes was determined according to proliferating activity of T
      lymphocytes, production of Interleukin-1 (IL-1) and estimation of subpopulations
      of T-leukocytes (T-helpers, T-suppressors). The patients were observed both
      before and 1-2.5 months after amiridin therapy. Considerable reduction of both IL
      1 production and proliferating activity of T-lymphocytes was observed after the
      treatment in 8 patients of 11. Their cognitive functioning after the therapy was
      either improved or stable by the moment of repeated observation. It is quite
      important that initial functional activity of lymphocytes was considerably higher
      in this group of patients as compared with the age-matched controls. Change for
      the worse in cognitive functions by the moment of the second examination was
      accompanied in 5 patients with an increase in IL-1 production as compared to the
      initial level. It is proposed that high level of IL-1 production by blood
      lymphocytes may be used as a criterion in selection of DAT patients for amiridin
      therapy.

PMID- 9634734
TI  - [A familial case of mental retardation syndrome linked to fragile X chromosome].

PMID- 9634735
TI  - [Adrenal insufficiency in nervous diseases].

PMID- 9634736
TI  - [Restoration of vision in toxic damage of visual pathways: traditional treatment
      combined with electrical stimulation].

PMID- 9634737
TI  - [Cerebrovascular insufficiency in Takayasu arteritis].

PMID- 9634738
TI  - [Various neurological aspects of critical care medicine].

PMID- 9634739
TI  - [The dysfunction of nervous regulation in the genesis of immune disorders with
      diseases of the nervous system].

PMID- 9634741
TI  - [Commentary on the article by E.M. Burtsev and E.B. Maletskaia "Clinical aspects
      and diagnostic criteria of benign intracranial hypertension in children" and
      their review "Benign intracranial hypertension in children"].

PMID- 9634740
TI  - [Evolutionary-biological conception of paraphilias].

PMID- 9634742
TI  - Out with the old, in with the new: time for a new drug development agency?

PMID- 9634743
TI  - BST off to a fast start, despite early stumbles.

PMID- 9634745
TI  - Republican Congress could unsettle U.S. biotech.

PMID- 9634744
TI  - The ethical roar of germ-line gene therapy.

PMID- 9634746
TI  - Enzymatic 7-ADCA: I said it couldn't be done.

PMID- 9634747
TI  - Comprehensive reform of the new drug regulatory process.

PMID- 9634748
TI  - Suicide microbes on the loose.

PMID- 9634749
TI  - Malarial epitopes expressed on the surface of recombinant tobacco mosaic virus.
AB  - Using malaria as a model disease, we engineered the surface of tobacco mosaic
      tobamovirus (TMV) for presentation of selected epitopes to the mammalian immune
      system. The TMV coat protein is a well-characterized and abundant self-assembling
      polymer previously shown to be a highly immunogenic carrier. Selected B-cell
      epitopes were either inserted into the surface loop region of the TMV coat
      protein or fused to the C terminus using the leaky stop signal derived from the
      replicase protein reading frame. Tobacco plants systemically infected with each
      of these constructs contained high titers of genetically stable recombinant
      virus, enabling purification of the chimeric particles in high yield. Symptoms
      induced in tobacco ranged from a normal mosaic pattern similar to that induced by
      the parental U1 strain to a unique bright yellow mosaic. As measured by
      quantitative ELISA against synthetic peptide standards, wild type TMV coat
      protein and fusion protein synthesized by the leaky stop mechanism coassembled
      into virus particles at the predicted ratio of approximately 20:1. Recombinant
      plant viruses have the potential to meet the need for scalable and cost effective
      production of subunit vaccines that can be easily stored and administered.

PMID- 9634750
TI  - Production of cephalosporin intermediates by feeding adipic acid to recombinant
      Penicillium chrysogenum strains expressing ring expansion activity.
AB  - We demonstrate a novel and efficient bioprocess for production of the
      cephalosporin intermediates, 7-aminocephalosporanic acid (7-ACA) or 7-amino
      deacetoxycephalosporanic acid (7-ADCA). The Streptomyces clavuligerus expandase
      gene or the Cephalosporium acremonium expandase-hydroxylase gene, with and
      without the acetyltransferase gene, were expressed in a penicillin production
      strain of Penicillium chrysogenum. Growth of these transformants in media
      containing adipic acid as the side chain precursor resulted in efficient
      production of cephalosporins having an adipyl side chain, proving that adipyl-6
      APA is a substrate for either enzyme in vivo. Strains expressing expandase
      produced adipyl-7-ADCA, whereas strains expressing expandase-hydroxylase produced
      both adipyl-7-ADCA and adipyl-7-ADAC (aminodeacetylcephalosporanic acid). Strains
      expressing expandase-hydroxylase and acetyltransferase produced adipyl-7-ADCA,
      adipyl-7-ADAC and adipyl-7-ACA. The adipyl side chain of these cephalosporins was
      easily removed with a Pseudomonas-derived amidase to yield the cephalosporin
      intermediates.

PMID- 9634751
TI  - Overproduction of encapsulated insecticidal crystal proteins in a Bacillus
      thuringiensis spo0A mutant.
AB  - The spo0A gene of Bacillus subtilis encodes the key factor involved in the
      initiation of sporulation. It was previously shown that the B. thuringiensis (Bt)
      cryIIIA gene, encoding a toxin active against coleopteran larvae, is
      overexpressed in an spo0A mutant of B. subtilis. In this paper we describe the
      construction of a Bt spo0A mutant strain and its use to produce insecticidal
      crystal proteins. The spo0A gene of Bt was cloned and identified by its ability
      to transform a B. subtilis spo0A mutant to prototrophy. Its nucleotide sequence
      is homologous to the B. subtilis gene. The spo0A gene was replaced in the Bt
      genome with a disrupted copy to give an Spo- strain unable to initiate
      sporulation. When the cryIIIA gene was cloned in the Bt spo0A mutant, large
      amounts of toxins were produced and accumulated to form a large crystal inclusion
      which remained encapsulated within the ghost cell. These encapsulated toxins were
      highly active against coleopteran larvae. We anticipate that the cryIIIA
      expression system and the Bt spo0A mutant will provide a convenient process to
      generate novel formulations of stabilized and environmentally safe Bt-based
      biopesticides.

PMID- 9634752
TI  - Plant seed oil-bodies as carriers for foreign proteins.
AB  - Plant seeds frequently store oils (triglycerides) in discrete organelles called
      oil-bodies. These are normally surrounded by a phospholipid half-unit membrane
      equipped with specialized proteins called oleosins. Oleosins are highly
      lipophilic proteins, are expressed at high levels in many seeds and are
      specifically targeted to oil-bodies. We have investigated the potential of
      oleosins to act as carriers for recombinant proteins by the production of
      translational fusions between oleosins and genes encoding proteins foreign to
      plant cells. We have shown that a fusion comprising a complete oleosin coding
      domain and a beta-glucuronidase coding sequence may be expressed specifically in
      the seeds of the oilseed crop plant, Brassica napus, and its product is correctly
      targeted with approximately 80% of the activity partitioning with oil-bodies.
      Recombinant oil-bodies may be used to facilitate separation of a recombinant
      protein from other cellular proteins. Using this approach, the desired protein
      may be cleaved from the oil-bodies using an endoprotease and further purified.
      Alternatively, a fusion protein which is enzymatically active and resides on the
      oil-bodies may be used directly in heterogeneous catalysis. In this application,
      after a round of catalysis the oil-bodies may be recovered and re-used several
      times without loss of activity. Thus the oil-bodies act as an immobilization
      matrix. The fusion protein is stable in dry seeds for long periods and when
      extracted has a half-life of 3-4 weeks on oil-bodies. Finally, the production of
      these recombinant oil-bodies is extremely inexpensive, offering a novel route to
      the manufacture of recombinant proteins.

PMID- 9634753
TI  - Tumor suppressor genes: prospects for cancer therapies.

PMID- 9634754
TI  - Production of polyhydroxyalkanoates, a family of biodegradable plastics and
      elastomers, in bacteria and plants.
AB  - In response to problems associated with plastic waste and its effect on the
      environment, there has been considerable interest in the development and
      production of biodegradable plastics. Polyhydroxyalkanoates (PHAs) are polyesters
      that accumulate as inclusions in a wide variety of bacteria. These bacterial
      polymers have properties ranging from stiff and brittle plastics to rubber-like
      materials. Because of their inherent biodegradability, PHAs are regarded as an
      attractive source of nonpolluting plastics and elastomers that can be used for
      specialty and commodity products. The possibility of producing PHAs in large
      scale and at a cost comparable to synthetic plastics has arisen from the
      demonstration of PHA accumulation in transgenic Arabidopsis plants expressing the
      bacterial PHA biosynthetic genes. Synergism between knowledge of the enzymes and
      genes contributing to PHA synthesis in bacteria and engineering of plant
      metabolic pathways will be necessary for the development of crop plants that
      produce biodegradable plastics.

PMID- 9634755
TI  - Red-shifted excitation mutants of the green fluorescent protein.
AB  - Using optimized combinatorial mutagenesis techniques and Digital Imaging
      Spectroscopy (DIS), we have isolated mutants of the cloned Aequorea victoria
      green fluorescent protein (GFP) that show red-shifted excitation spectra similar
      to that of Renilla reniformis GFP. Selective excitation of wild-type versus Red
      Shifted GFP (RSGFP) enables spectral separation of these proteins. Six contiguous
      codons spanning the tyrosine chromophore region were randomized and sequence
      analysis of the mutants revealed a tyrosineglycine consensus. These mutants will
      enable the simultaneous analysis of two promoters or proteins per cell or
      organism. In consideration of the multitude of applications which are developing
      for GFP alone, we envisage that spectrally shifted fluorescent proteins will be
      of value to a diversity of research programs, including developmental and cell
      biology, drug-screening, and diagnostic assays.

PMID- 9634756
TI  - Engineered Fv fragments as a tool for the one-step purification of integral
      multisubunit membrane protein complexes.
AB  - The preparation of pure and homogeneous membrane proteins or membrane protein
      complexes is time consuming, and the yields are frequently insufficient for
      structural studies. To circumvent these problems we established an indirect
      immunoaffinity chromatography method based on engineered Fv fragments. cDNAs
      encoding the variable domains of hybridoma-derived antibodies raised against
      various membrane proteins were cloned and expressed in Escherichia coli. The Fv
      fragments were engineered to serve as bifunctional adaptor molecules. The Fv
      fragment binds to the epitope of the membrane protein, while the Strep tag
      affinity peptide, which was fused to the carboxy-terminus of the VH chain,
      immobilizes the antigen-Fv complex on a streptavidin sepharose column. The
      usefulness of this technique is illustrated with membrane protein complexes from
      Paracoccus denitrificans, namely, the cytochrome c oxidase (EC 1.9.3.1), the
      ubiquinol:cytochrome c oxidoreductase (EC 1.10.2.2), and subcomplexes or
      individual subunits thereof. These membrane proteins were purified simply by
      combining the crude P. denitrificans membrane preparation with the E. coli
      periplasmic cell fraction containing the corresponding Fv fragment, followed by
      solubilization and streptavidin affinity chromatography. Pure and highly active
      membrane protein complexes were eluted in the Fv-bound form using diaminobiotin
      for mild competitive displacement of the Strep tag. The affinity column could
      thus be reused under continuous operation for several months. Five to 10 mg of
      membrane protein complexes could be obtained without any detectable impurities
      within five hours.

PMID- 9634757
TI  - An allosteric hammerhead ribozyme.
AB  - We have constructed an RNA molecule containing a hammerhead ribozyme that is
      under allosteric control. In the inactive state, the RNA enzyme is unable to
      cleave a suitable substrate. The formation of the active state of the ribozyme is
      triggered by a specific interaction with a DNA oligonucleotide effector that is
      complementary to a single-stranded loop in the RNA enzyme molecule. Other DNA or
      RNA molecules containing unrelated nucleotide sequences do not function as
      allosteric effectors. This work demonstrates the feasibility of designing RNA
      enzymes that are specifically activated in response to an artificially designed
      molecular recognition event. Such enzymes may have practical applications.

PMID- 9634758
TI  - Binding epitope of somatostatin defined by phage-displayed peptide libraries.
AB  - We have developed a versatile phagemid system to display peptides on the surface
      of M13 bacteriophage at a copy number which approaches monovalency. In this
      system, a phagemid encodes a peptide fused to the amino-terminus of the second
      domain (dII) of the minor coat protein pIII under control of the inducible lac
      promoter. The fusion protein is displayed in combination with several copies of
      wild-type pIII on the surface of phage. Two diverse random octapeptide libraries,
      one linear and one which contained flanking cysteines capable of forming
      disulfide bridges, were were generated using an in vitro mutagenesis approach and
      affinity selected on an anti-somatostatin mAb. Peptides with high affinity for
      the mAb were enriched only from the cyclic library and the tetrapeptide, FWKT,
      was identified by consensus as the binding epitope. The selected peptides
      exhibited not only the primary amino acid sequence but also shared structural
      features with somatostatin. One peptide, CRFWKTWC, also exhibited nanomolar
      affinities for the five known somatostatin receptor subtypes. This system can
      easily be adapted to display individual peptides or a wide range of custom
      peptide libraries.

PMID- 9634759
TI  - Recent advances in the large scale fermentation of Neisseria meningitidis group B
      for the production of an outer membrane protein complex.
AB  - The Outer Membrane Protein Complex (OMPC) of the bacterium Neisseria meningitidis
      group B has been used successfully as a protein carrier in a Haemophilus
      influenza type b (Hib) polysaccharide conjugate vaccine and a Streptococcus
      pneumoniae (Pn) polysaccharide conjugate vaccine to elicit antipolysaccharide
      immune responses in young infants. The OMPC carrier is derived by detergent
      extraction of whole cells and, thus, the consistent generation of suitable
      biomass is central to an effective production process. Therefore, we have
      developed a large-scale, high-cell density (5 g/L dry cell weight) fermentation
      process for the cultivation of N. meningitidis B11. Since current requirements
      for the production of human biologics mandate strict control of all aspects of
      the manufacturing process, several key features of the process, including a
      chemically defined medium and a rational event-based harvest criterion, support
      current good manufacturing practice (cGMP) and increased productivity.

PMID- 9634760
TI  - Tight transcriptional control mechanism ensures stable high-level expression from
      T7 promoter-based expression plasmids.
AB  - One of the more efficient systems for high-level expression of cloned genes in
      Escherichia coli makes use of a phage T7 late promoter whose activity depends on
      a regulatable transcription unit supplying the specific T7 RNA polymerase. Using
      various T7 RNA polymerase/T7 promoter-based vector host systems with differential
      control on expression of the T7 RNA polymerase, we document that leaky expression
      of the latter is responsible for the frequently observed loss of the culture's
      ability to express genes of interest. We further show that the inability to
      achieve detectable expression levels can be overcome by using a tightly repressed
      expression system. We describe a novel and efficient control system in which
      basal level expression of T7 RNA polymerase is attenuated by a series of tandemly
      arranged transcription terminators. The plasmids also incorporate the phage
      lambda-derived nutL/N protein antitermination function, allowing conditional
      reversion of attenuation upon induction. The applicability of the system is
      illustrated by the strictly regulatable, high-level production of several
      cytokines of human and murine origin.

PMID- 9634761
TI  - FDA advisory panel okays HIV vaccine.

PMID- 9634763
TI  - Drug firms need biotech drug discovery.

PMID- 9634762
TI  - Biotech plays big role in efforts against AIDS.

PMID- 9634764
TI  - The vector void in gene therapy.

PMID- 9634765
TI  - Virtual spectroscopy for fun and profit.

PMID- 9634767
TI  - Generation of rabbit monoclonal antibody fragments from a combinatorial phage
      display library and their production in the yeast Pichia pastoris.
AB  - We have applied the combinatorial immunoglobulin library and phage display
      technologies to generate monoclonal rabbit single-chain Fv (scFv) antibody
      fragments specific for recombinant human leukemia inhibitory factor (rhLIF). The
      B cell immunoglobulin repertoire of an immunized rabbit was immortalized by the
      combinatorial cloning of the rearranged variable domains of light (VL) and heavy
      (VH) chains. Affinity selection of the library displaying the rabbit antibody
      domains on the phage surface resulted in the isolation of phage encoding scFv
      antibodies which specifically bind to the antigen. We utilized the methylotrophic
      yeast Pichia pastoris for high level secretion of soluble and functional scFv
      antibody fragment. More than 100 mg/L of pure and functional rabbit anti-rhLIF
      scFv antibody was obtained directly from the P. pastoris culture supernatant by
      one-step affinity chromatography.

PMID- 9634768
TI  - A hybrid baculovirus-bacteriophage T7 transient expression system.
AB  - A hybrid recombinant baculovirus-bacteriophage T7 expression system was developed
      for transient expression in insect cells of plasmids with foreign genes provided
      with a T7 promoter. The coding sequence for T7 RNA polymerase, with or without a
      nuclear localization signal, was inserted into the genome of Autographa
      californica nuclear polyhedrosis virus. Recombinant viruses stably expressed T7
      RNA polymerase in insect cells. Upon transfection of infected insect cells with
      plasmids containing the genes for chloramphenicol acetyltransferase (CAT), the
      hepatitis B virus precore-, core- or e- antigens under control of the T7
      promoter, transient expression of these genes was detected by ELISA. The results
      obtained indicate that this baculovirus/T7 system provides a simple and widely
      applicable tool for transient gene expression studies.

PMID- 9634769
TI  - Phage libraries displaying cyclic peptides with different ring sizes: ligand
      specificities of the RGD-directed integrins.
AB  - We have isolated selective ligands to the cell surface receptors of fibronectin
      (alpha 5 beta 1 integrin), vitronectin (alpha v beta 3 and alpha v beta 5
      integrins) and fibrinogen (alpha IIb beta 3 integrin) from phage libraries
      expressing cyclic peptides. A mixture of libraries was used that express a series
      of peptides flanked by a cysteine residue on each side (CX5C, CX6C, CX7C) or only
      on one side (CX9) of the insert. A majority of the integrin-binding sequences
      derived from the CX9 library contained another cysteine, indicating preferential
      selection of conformationally constrained cyclic peptides. Each of the four
      integrins studied primarily selected RGD-containing phage sequences but favored
      different ring sizes and different flanking residues around the RGD motif. A
      cyclic peptide ACRGDGWCG was synthesized based on a phage sequence that bound
      particularly avidly to the alpha 5 beta 1 integrin. This peptide inhibited cell
      attachment to fibronectin at about 5-fold lower concentrations than the most
      potent cyclic peptides described earlier. The most interesting structure appeared
      to contain two disulphide bonds. One such peptide, ACDCRGDCFCG, was synthetized
      and shown to be at least 20-fold more potent inhibitor of alpha v beta 5- and
      alpha v beta 3-mediated cell attachment to vitronectin than similar peptides with
      a single disulphide bond and 200-fold more potent than commonly used linear RGD
      peptides. These results emphasize the importance of conformational restriction as
      a means of improving the potency of integrin-binding peptides and point to a new
      way of designing effective peptides by resticting the peptide conformation with
      more than one cyclizing bond.

PMID- 9634770
TI  - A chromosome integration system for stable gene transfer into Thermus flavus.
AB  - We have developed a chromosomal integration system for gene transfer into the
      extreme thermophile Thermus flavus. The system relies on integration at the site
      of leuB (3-isopropylmalate dehydrogenase) which was cloned from T. flavus. The
      leuB gene was insertionally inactivated in vitro with a thermostable kanamycin
      resistance gene and transformed in single-copy into the chromosome of T. flavus
      on a plasmid vector. Gene replacement strains required leucine for growth, were
      stably kanamycin-resistant and could grow in the presence of kanamycin at
      temperatures up to 55 degrees C.

PMID- 9634771
TI  - A computer program to determine a protein sequence from an amino acid analysis.
AB  - We have developed a computational method for analyzing the proteolytic products
      of a protein, knowing its sequence and the amino acid percentages of its
      products. For all fragments, amino acid percentages are calculated and compared
      to the experimental results (calculating the error within the experiment). The
      program keeps the best fitted fragment using a least squared method. This program
      was written to determine the sequence of the proteolytic products that appeared
      during the purification of annexin I domain 2. The reliability of the method was
      verified in this case. However the latter depends on the length and on the amino
      acid composition of the entire protein and of its fragments. This program may be
      suitable for analyzing the sequence of the products in any protease digestion,
      whether designed or accidental.

PMID- 9634772
TI  - For AIDS, the FDA may be reforming itself.

PMID- 9634773
TI  - Group I introns: new molecular mechanisms for mRNA repair.

PMID- 9634774
TI  - RNase P in research and therapy.

PMID- 9634775
TI  - To treat or not to treat: that is the question for serum.

PMID- 9634776
TI  - Combinatorial drug discovery: which methods will produce the greatest value?
AB  - Combinatorial strategies are important new approaches to drug discovery, and it
      seems quite likely that they will result in the discovery of interesting
      potential pharmaceuticals. However, it is less clear whether combinatorial
      approaches will result in quantum advances in therapeutics. Nor is there general
      agreement about the factors most important in defining how combinatorial
      strategies will provide value to the discovery of lead and therapeutic compounds.
      In this review, we propose criteria that define the value of combinatorial
      strategies and categorize the various approaches by: (a) the type of chemical
      space to be searched, (b) the tactics employed to synthesize and screen
      libraries, and (c) the structures of individual molecules in libraries. We
      evaluate the strengths and weaknesses of the various strategies and suggest
      milestones that can help to track their success.

PMID- 9634777
TI  - Amplification of a chimeric Bacillus gene in chloroplasts leads to an
      extraordinary level of an insecticidal protein in tobacco.
AB  - The Bacillus thuringiensis (Bt) crystal toxins are safe biological insecticides,
      but have short persistance and are poorly effective against pests that feed
      inside plant tissues. Production of effective levels of these proteins in plants
      has required resynthesis of the genes encoding them. We report that amplification
      of an unmodified crylA(c) coding sequence in chloroplasts up to approximately
      10,000 copies per cell resulted in the accumulation of an unprecedented 3-5% of
      the soluble protein in tobacco leaves as protoxin. The plants were extremely
      toxic to larvae of Heliothis virescens, Helicoverpa zea, and Spodoptera exigua.
      Since the plastid transgenes are not transmitted by pollen, this report has
      implications for containment of Bt genes in crop plants. Furthermore,
      accumulation of insecticidal protein at a high level will facilitate improvement
      in the management of Bt resistant insect populations.

PMID- 9634778
TI  - Expression of thioredoxin random peptide libraries on the Escherichia coli cell
      surface as functional fusions to flagellin: a system designed for exploring
      protein-protein interactions.
AB  - We have developed a system for probing protein/protein interactions which makes
      use of the bacterial flagellum to display random peptide libraries on the surface
      of E. coli. In developing the system the entire coding sequence of E. coli
      thioredoxin (trxA) was inserted into a dispensable region of the gene for
      flagellin (fliC), the major structural component of the E. coli flagellum. The
      resulting fusion protein (FLITRX) was efficiently exported and assembled into
      partially functional flagella on the bacterial cell surface. A diverse library of
      random dodecapeptides were displayed in FLITRX on the exterior of E. coli as
      conformationally constrained insertions into the thioredoxin active-site loop, a
      location known to be a highly permissive site for the insertion of exogenous
      peptide sequences into native thioredoxin. To demonstrate that members of this
      library could be bound and selected via specific protein/protein interactions to
      a target protein, a method was devised to enable efficient isolation of those
      bacteria displaying peptides with affinity to immobilized antibodies. We have
      unambiguously mapped three different antibody epitopes using this method.
      Peptides selected as FLITRX active-site fusions retain their binding specificity
      when made as native thioredoxin active-site loop fusions. This will facilitate
      future structural characterizations and broaden the general utility of the system
      for exploring other classes of protein-protein interactions.

PMID- 9634779
TI  - Calmodulin as a versatile tag for antibody fragments.
AB  - Calmodulin is a highly acidic protein (net charge -24 at pH 8.0 in the absence of
      calcium) that binds to peptide and organic ligands with high affinity (Ka > 10(9)
      M-1) in a calcium-dependent manner. We have exploited these properties to develop
      calmodulin as a versatile tag for antibody fragments. Fusions of calmodulin with
      single chain Fv fragments (scFv) could be expressed by secretion from bacteria in
      good yield (5-15 mg/l in shaker flasks), and purified from periplasmic lysates or
      broth to homogeneity in a single step, either by binding to anion-exchange resin
      (DEAE-Sephadex), or to an organic ligand of calmodulin (N-(6-aminohexyl)-5-chloro
      1-naphthalenesulfonamide-agarose). The antibody fusions could be detected by
      binding of fluorescently labeled peptide ligands, as illustrated by their use in
      confocal microscopy, fluorescent activated cell sorting and "band shift" gel
      electrophoresis. Moreover, the interaction between calmodulin and peptide ligands
      could provide a means of heterodimerization of proteins, as illustrated by the
      assembly of an antibody-calmodulin fusion with maltose binding protein tagged
      with a peptide ligand of calmodulin.

PMID- 9634780
TI  - Surface expression and ligand-based selection of cDNAs fused to filamentous phage
      gene VI.
AB  - We describe a novel phage display system that affords the surface expression and
      hence affinity selection of cDNAs. The strategy is based on a new approach to
      functionally display proteins on filamentous phage through the attachment to the
      C-terminus of the minor coat protein VI. The utility of the method was evaluated
      using a cDNA library derived from the parasite Ancylostoma caninum. cDNA
      sequences were fused in each of the three reading frames to the 3'-end of the M13
      gene VI expressed by a phagemid vector. Phages rescued from this cDNA expression
      library were subjected to biopanning against two serine proteases, trypsin and
      the human coagulation factor Xa. This led to the identification of cDNAs encoding
      novel members of two different families of serine protease inhibitors. The
      authenticity of the cDNA selected with trypsin as the target was demonstrated by
      purifying the encoded potent Kunitz-type inhibitor from an Ancylostoma caninum
      extract. The rapid isolation of specific cDNAs with the protein VI monovalent
      display system should facilitate the search for novel biologically important
      ligands.

PMID- 9634781
TI  - Phosphoric acid entrapment leads to apparent protein heterogeneity.
AB  - Recombinant proteins produced in prokaryotes or eukaryotes show certain types of
      heterogeneity due to post-translational modifications. Some preparations of a
      soluble interferon gamma receptor, produced in Escherichia coli, appeared as a
      double band with slightly different mobilities in non-reducing sodium
      dodecylsulfate and native polyacrylamide gels. Ion spray mass spectrometry showed
      that the two forms had a mass difference of one to three multiples of 97 +/- 2 D.
      Gas chromatography-mass spectrometry analysis revealed the presence of phosphoric
      acid in the hydrolysate and in the intact protein. The more slowly migrating
      protein species had trapped molecules of phosphoric acid during the protein
      extraction. Most of the trapped phosphoric acid was loosely associated with the
      protein. One to three molecules were tightly, but non-covalently linked per
      receptor molecule. Phosphoric acid entrapment did not affect biological activity
      and most likely did not affect protein conformation. The species carrying
      phosphoric acid showed higher solubility. Trapping of phosphoric acid by proteins
      may be a general phenomenon and the results reported here thus useful in the
      characterization of other recombinant proteins.

PMID- 9634782
TI  - Production of recombinant proteins in Chinese hamster ovary cells using a protein
      free cell culture medium.
AB  - The growth-factor prototrophic Chinese hamster ovary (CHO) SSF3 cell line was
      previously adapted for growth in serum-free media. Here we present a newly
      designed medium which allows these cells to grow in the absence of any
      exogenously added growth factors. To investigate the capacity of CHO SSF3 cells
      for the efficient production of recombinant proteins in protein-free media,
      expression plasmids containing either a human single chain urokinase-type
      plasminogen activator (uPA)-encoding cDNA or a humanized immunoglobulin G (IgG)
      kappa light chain cDNA were introduced by transfection. The tryptophan synthase
      (trpB) gene of Escherichia coli was used as a dominantly acting selection marker
      allowing the cells to survive in a medium containing indole in place of
      tryptophan. Some of the clones obtained exhibited a stable uPA expression over a
      period of several months under selective conditions and the yields were up to 74
      mg of uPA/l in a bioreactor and the productivity was around 40 mg/day per 10(9)
      cells. The yields of IgG light chains were up to 118 mg/l and the productivity
      was in the order of 56 mg/day per 10(9) cells in a bioreactor. These results
      demonstrate the potential of CHO SSF3 cells for the efficient production of
      recombinant proteins under protein-free conditions.

PMID- 9634783
TI  - Review of NIHRAC focuses on gene therapy.

PMID- 9634784
TI  - Pharmacoeconomics: drug pricing's new guise.

PMID- 9634785
TI  - The era of intracellular nucleic acid technology.

PMID- 9634786
TI  - Clinical systems for the production of human cells and tissues.

PMID- 9634787
TI  - Phytoremediation: a novel strategy for the removal of toxic metals from the
      environment using plants.
AB  - Toxic metal pollution of waters and soils is a major environmental problem, and
      most conventional remediation approaches do not provide acceptable solutions. The
      use of specially selected and engineered metal-accumulating plants for
      environmental clean-up is an emerging technology called phytoremediation. Three
      subsets of this technology are applicable to toxic metal remediation: (1)
      Phytoextraction--the use of metal-accumulating plants to remove toxic metals from
      soil; (2) Rhizofiltration--the use of plant roots to remove toxic metals from
      polluted waters; and (3) Phytostabilization--the use of plants to eliminate the
      bioavailability of toxic metals in soils. Biological mechanisms of toxic metal
      uptake, translocation and resistance as well as strategies for improving
      phytoremediation are also discussed.

PMID- 9634788
TI  - Antibody VH domains as small recognition units.
AB  - To develop immunoglobulin based recognition units of minimum size, a human heavy
      chain variable domain (VH) was designed for selection of phage displayed VH. Non
      specific binding of the VH through its interface for the light chain variable
      domain (VL) was prevented through three mutations (G44E, L45R and W47G) in this
      interface. These mutations were introduced to mimic camelid antibody heavy chains
      naturally devoid of light chain partners. The third hypervariable loop of the
      modified VH was then randomised to yield a repertoire of 2 x 10(8) independent
      clones, which was displayed on phage and selected through antigen binding. VH
      clones specific for hapten and protein antigens were isolated. Soluble VH was
      expressed with an isoleucine residue at position 47 to improve expression and
      stability compared to VH containing a glycine residue at this position, which
      however was preferable for phage selection. Affinities of soluble VH for hapten
      were between 100 nM and 400 nM. The VH domains were highly specific, stable and
      well expressed in Escherichia coli. These positive biophysical properties and
      their small size make them attractive for biotechnological applications.

PMID- 9634789
TI  - Genetic transformation of banana and plantain (Musa spp.) via particle
      bombardment.
AB  - We have developed a simple protocol to allow the production of transgenic banana
      plants. Foreign genes were delivered into embryogenic suspension cells using
      accelerated particles coated with DNA. Bombardment parameters were optimized for
      a modified particle gun resulting in high levels of transient expression of the
      beta-glucuronidase gene in both banana and plantain cells. Bombarded banana cells
      were selected with hygromycin and regenerated into plants. Molecular and
      histochemical characterization of transformants revealed the stable integration
      of the transferred genes into the banana genome.

PMID- 9634790
TI  - Aggregation of a lyophilized pharmaceutical protein, recombinant human albumin:
      effect of moisture and stabilization by excipients.
AB  - In the presence of water vapor at 37 degrees C, lyophilized recombinant human
      albumin (rHA) undergoes intermolecular thiol-disulfide interchange, eventually
      forming high-molecular-weight, water-insoluble aggregates. The relationship
      between the extent of aggregation and the water content of the lyophilized
      protein was bell-shaped, with maximum aggregation (over 80% after one day) at
      approximately 50 g water per 100 g dry protein, corresponding to incubation at
      96% relative humidity. Nineteen different excipients were co-lyophilized with rHA
      to test their ability to inhibit aggregation under these conditions. These
      compounds included low- and high-molecular-weight sugars, as well as various
      organic acids (amino, hydroxy, and aliphatic), and the simple inorganic salt
      sodium chloride. Seven of them afforded complete stabilization of rHA against
      moisture-induced aggregation. The stabilizing potency of the excipients
      correlated with their water-sorbing capability, presumably due to increasing the
      moisture level in the vicinity of rHA.

PMID- 9634791
TI  - A system for production of commercial quantities of human lactoferrin: a broad
      spectrum natural antibiotic.
AB  - We previously reported the production of limited quantities of biologically
      active recombinant human lactoferrin in the filamentous fungus Aspergillus
      oryzae. In the present study, we report a modification of this production system
      combined with a classical strain improvement program that has enabled production
      of levels of recombinant human lactoferrin in excess of 2 g/l. The protein was
      expressed in Aspergillus awamori as a glucoamylase fusion polypeptide which was
      secreted into the growth medium and processed to mature human lactoferrin by an
      endogenous KEX-2 peptidase. The recombinant protein retains full biological
      activity in terms of its ability to bind iron and human enterocyte receptors.
      Furthermore, the recombinant protein functions as a potent broad spectrum
      antimicrobial protein.

PMID- 9634792
TI  - Improved N-terminal processing of recombinant proteins synthesized in Escherichia
      coli.
AB  - Preparations of rHMfA (recombinant histone A from Methanothermus fervidus)
      synthesized in E. coli by the heterologous expression of the hmfA gene were found
      to contain a mixture of rHMfA molecules, approximately 40% that retained the N
      terminal formyl-methionyl residue (f-met-rHMfA), approximately 50% that lacked
      the formyl moiety but retained the methionyl residue (met-rHMfA), and only
      approximately 10% that had lost both components of the protein synthesis
      initiating amino acid residue and therefore had the same N-terminal sequence as
      native HMfA molecules synthesized in Mt. fervidus. Expression of the hmfA gene in
      E. coli cells grown in the presence of trimethoprim and thymidine, coupled with
      the concurrent over-expression of a methionine aminopeptidase-encoding map gene,
      has been shown to overcome this N-terminal heterogeneity problem and to result in
      rHMfA preparations in which > 85% of the molecules have the fully processed,
      native N-terminal sequence. This procedure should be generally useful for
      ensuring N-terminal processing of recombinant proteins synthesized in E. coli.

PMID- 9634793
TI  - Protease-dependent streptomycin sensitivity in E. coli--a system for protease
      inhibitor selection.
AB  - We have developed a bacterial cell system in which the activity of an expressed
      heterologous protease confers a dominant streptomycin-sensitive (strs) phenotype
      on the cell. This phenotype owes its high selectivity to the fact that
      streptomycin (strep) resistance, which is conferred on E. coli by mutants of
      ribosomal protein S12, is highly recessive to strep sensitivity. Thus, when strep
      resistant (strr) strains of E. coli are transformed to co-express the wild-type
      allele of S12 in addition to the mutant allele, their sensitivity to strep
      increases by a factor of 100-1000. Similarly, we found that when the same strr
      strains were transformed to co-express a heterologous protease and an inactive
      fusion of S12 with a substrate of the protease, the strep sensitivity of the
      cells increased approximately 100-fold. This effect was strictly dependent on
      correct cleavage of the S12 precursor, required only modest levels of expression
      of protease and substrate, and could be competitively inhibited by co-expression
      of an alternative substrate gene. This system thus appears to be well-suited to
      the identification of protease inhibitors, either by selection from libraries of
      endogenously expressed random peptide-encoding genes, or by screening synthetic
      or natural products libraries. Protease-dependent dominant phenotypes may be more
      sensitive and appropriate than the more commonly used recessive phenotypes for
      proteases which are activating enzymes.

PMID- 9634794
TI  - Remodeling MMPIs.

PMID- 9634795
TI  - Biomaterials in tissue engineering.
AB  - Biomaterials play a pivotal role in field of tissue engineering. Biomimetic
      synthetic polymers have been created to elicit specific cellular functions and to
      direct cell-cell interactions both in implants that are initially cell-free,
      which may serve as matrices to conduct tissue regeneration, and in implants to
      support cell transplantation. Biomimetic approaches have been based on polymers
      endowed with bioadhesive receptor-binding peptides and mono- and
      oligosaccharides. These materials have been patterned in two- and three
      dimensions to generate model multicellular tissue architectures, and this
      approach may be useful in future efforts to generate complex organizations of
      multiple cell types. Natural polymers have also played an important role in these
      efforts, and recombinant polymers that combine the beneficial aspects of natural
      polymers with many of the desirable features of synthetic polymers have been
      designed and produced. Biomaterials have been employed to conduct and accelerate
      otherwise naturally occurring phenomena, such as tissue regeneration in wound
      healing in the otherwise healthy subject; to induce cellular responses that might
      not be normally present, such as healing in a diseased subject or the generation
      of a new vascular bed to receive a subsequent cell transplant; and to block
      natural phenomena, such as the immune rejection of cell transplants from other
      species or the transmission of growth factor signals that stimulate scar
      formation. This review introduces the biomaterials and describes their
      application in the engineering of new tissues and the manipulation of tissue
      responses.

PMID- 9634796
TI  - Transgenic canola and soybean seeds with increased lysine.
AB  - We have increased the lysine content in the seeds of canola and soybean plants by
      circumventing the normal feedback regulation of two enzymes of the biosynthetic
      pathway, aspartokinase (AK) and dihydrodipicolinic acid synthase (DHDPS). Lysine
      feedback-insensitive bacterial DHDPS and AK enzymes encoded by the
      Corynebacterium dapA gene and a mutant E. coli lysC gene, respectively, were
      linked to a chloroplast transit peptide and expressed from a seed-specific
      promoter in transgenic canola and soybean seeds. Expression of Corynebacterium
      DHDPS resulted in more than a 100-fold increase in the accumulation of free
      lysine in the seeds of canola; total seed lysine content approximately doubled.
      Expression of Corynebacterium DHDPS plus lysine-insensitive E. coli AK in soybean
      transformants similarly caused several hundred-fold increases in free lysine and
      increased total sed lysine content by as much as 5-fold. Accumulation of alpha
      amino adipic acid (AA) in canola and saccharopine in soybean, which are
      intermediates in lysine catabolism, was also observed.

PMID- 9634797
TI  - Whole-virus vaccine development by continuous culture on a complementing host.
AB  - We have evaluated an adaptive strategy for generating whole-virus vaccines using
      a bacteriophage model. Wildtype phage T7 was cultivated in a two-stage continuous
      stirred-tank reactor (CSTR) utilizing a recombinant E. coli host that
      constitutively expressed T7 RNA polymerase, an essential enzyme of the early
      viral metabolism. Over the course of 180 generations a diversity of phage
      variants emerged, outgrew the wildtype, and were subsequently eclipsed by yet
      fitter variants, based on host-ranges, restriction patterns, and one-step growth
      responses of isolated clones. The fittest variant, which required complementation
      by the recombinant host in order to grow, deleted at least 12 percent of its
      genome and replicated twice as fast as the wildtype. Moreover, this variant was
      immunogenically indistinguishable from the wildtype, based on cross-reactivities
      of antisera raised against both. These results suggest the feasibility of the
      proposed strategy for the development of safe whole-virus vaccines.

PMID- 9634798
TI  - Expression of multiple eukaryotic genes from a single promoter in Nicotiana.
AB  - We engineered an expression unit composed of three eukaryotic genes driven by a
      single plant-active promoter and demonstrated functional expression in planta.
      The individual genes were linked as translational fusions to produce a
      polyprotein using spacer sequences encoding specific heptapeptide cleavage
      recognition sites for NIa protease of tobacco vein mottling virus (TVMV). The NIa
      gene itself was included as the second gene of the multi-gene unit. The first and
      third genes, obtained from the TR region of pTi15955, encoded enzymatic functions
      associated with the mannityl opine biosynthetic pathway. The mannityl opine
      conjugase gene (mas2) was the first unit of the construct and provided the native
      plant-active promoter and 5' untranslated regulatory sequence. The third gene
      (mas1), encoding the mannityl opine reductase, furnished the native 3'
      untranslated region. Cis-processing of the polyprotein by the NIa protease domain
      was demonstrated in vitro using rabbit reticulocyte lysate and wheat germ cell
      free translation systems. Tobacco plant cells transformed with the multi-gene
      unit produced detectable levels of mannopine, mannopinic acid, and their
      biosynthetic intermediates, deoxyfructosyl-glutamate and deoxyfructosyl
      glutamine. This indicates that the polygene construct results in a set of
      functional enzymatic activities that constitute a complete metabolic pathway.

PMID- 9634799
TI  - N-glycosylation of recombinant human interferon-gamma produced in different
      animal expression systems.
AB  - Recombinant human interferon-gamma (IFN-gamma) was expressed in Chinese hamster
      ovary cells, baculovirus-infected Sf9 insect cells and the mammary gland of
      transgenic mice. The N-linked carbohydrate populations associated with both Asn25
      and Asn97 glycosylation sites were characterized by matrix-assisted laser
      desorption/ionization-mass spectrometry (MALDI-MS) in combination with
      exoglycosidase array sequencing. A site-specific analysis of dual (2N) and single
      (1N) site-occupancy variants of IFN-gamma derived from Chinese hamster ovary
      cells showed that N-glycans were predominantly of the complex bi- and
      triantennary type. Although Asn25-linked glycans were substituted with a core
      fucose residue, Asn97 N-glycans were predominantly non-fucosylated, and truncated
      complex and high-mannose oligosaccharide chains were also evident. Transgenic
      mouse derived IFN-gamma exhibited considerable site-specific variation in N
      glycan structures. Asn25-linked carbohydrates were of the complex, core
      fucosylated type, Asn97-linked carbohydrates were mainly of the oligomannose
      type, with smaller proportions of hybrid and complex N-glycans. Carbohydrates
      associated with both glycosylation sites of IFN-gamma from Sf9 insect cells were
      mainly tri-mannosyl core structures, with fucosylation confined to the Asn25
      site. These data demonstrate the profound influence of host cell type and protein
      structure on the N-glycosylation of recombinant proteins.

PMID- 9634800
TI  - Improved adenovirus vector provides herpes simplex virus ribonucleotide reductase
      R1 and R2 subunits very efficiently.
AB  - We have constructed a new adenovirus (Ad) expression vector, pAdBM5, that allows
      for the production of unprecedented levels of recombinant protein in the human
      293 cell line using the Ad expression system. The main feature of this vector is
      a combination of enhancer sequences that increases the activity of the ectopic
      major late promoter (MLP) in recombinant Ad. In 293 cells infected with helper
      free Ad recombinants generated with the pAdBM5 transfer vector, both herpes
      simplex virus (HSV) ribonucleotide reductase R1 and R2 subunits represent the
      most abundant polypeptides, accounting for as much as 15-20% of total cellular
      proteins. Our data suggest that this level of expression is probably very close
      to the upper limit of the system. Furthermore, when compared to the widely
      utilized baculovirus (Bac)/Sf9 expression system, the improved Ad vector showed a
      better performance for the production and purification of active HSV-2
      ribonucleotide reductase R1 and R2 subunits. The R2 subunit was about 5-fold more
      abundant in recombinant Ad-infected 293 cells than in Bac-infected Sf9 cells
      while the R1 subunit was produced at roughly similar levels with either system.
      However, the amount of active soluble R1 obtained from recombinant Ad-infected
      293 cells was at least 5 times higher because most of the R1 produced in Sf9
      cells was insoluble.

PMID- 9634801
TI  - Structural and functional epitopes in the growth hormone receptor complex.

PMID- 9634802
TI  - Extremozymes: expanding the limits of biocatalysis.
AB  - The study of enzymes isolated from organisms inhabiting unconventional ecosystems
      has led to the realization that biocatalysis need not be constrained to mild
      conditions and can be considered at pH's, temperatures, pressures, ionic and
      solvent environments long thought to be destructive to biomolecules. Parallel to
      this, it has been demonstrated that even conventional enzymes will catalyze
      reactions in solvents other than water. However, the intrinsic basis for
      biological function under extreme conditions is only starting to be addressed, as
      are associated applications. This was the focus of a recent NSF/NIST-sponsored
      workshop on extremozymes. Given the information acquired from the study of
      extremozymes, modification of enzymes to improve their ranges of stability and
      activity remains a possibility. Ultimately, by expanding the range of conditions
      suitable for enzyme function, new opportunities to use biocatalysis will be
      created.

PMID- 9634803
TI  - Directed evolution of a subtilisin with calcium-independent stability.
AB  - Extracellular proteases of the subtilisin-class depend upon calcium for
      stability. Calcium binding stabilizes these proteins in natural extracellular
      environments, but is an Achilles' heel in industrial environments which contain
      high concentrations of metal chelators. Here we direct the evolution of calcium
      independent stability in subtilisin BPN'. By deleting the calcium binding loop
      from subtilisin, we initially destabilize the protein but create the potential to
      use new structural solutions for stabilization. Analysis of the structure and
      stability of the loop-deleted prototype followed by directed mutagenesis and
      selection for increased stability resulted in a subtilisin mutant with native
      like proteolytic activity but 1000-times greater stability in strongly chelating
      conditions.

PMID- 9634804
TI  - Biological production of semisynthetic opiates using genetically engineered
      bacteria.
AB  - Semisynthetic derivatives of morphine and related alkaloids are in widespread
      clinical use. Due to the complexity of these molecules, however, chemical
      transformations are difficult to achieve in high yields. We recently identified
      the powerful analgesic hydromorphone as an intermediate in the metabolism of
      morphine by Pseudomonas putida M10. Here we describe the construction of
      recombinant strains of Escherichia coli that express morphine dehydrogenase and
      morphinone reductase. These strains are capable of efficiently transforming the
      naturally occurring alkaloids morphine and codeine to hydromorphone and the
      antitussive hydrocodone, respectively. Our results demonstrate the potential for
      recombinant DNA technology to provide biological routes for the synthesis of
      known and novel semisynthetic opiate drugs.

PMID- 9634805
TI  - Polyclonal preparations of anti-tetanus toxoid antibodies derived from a
      combinatorial library confer protection.
AB  - We have compared the in vivo therapeutic potential of anti-tetanus toxin (TT)
      human Fab antibodies derived from a combinatorial phage display library to
      established polyclonal and monoclonal reagents. The oligoclonality and fine
      specificity distribution of the synthetic anti-TT Fab preparations was comparable
      to the antibody spectrum present in the donor serum and the affinities determined
      for the synthetic phage-bound Fab (Phab) and soluble Fab were in the same range
      as their monoclonal and polyclonal counterparts. On a weight basis, the
      protective capacity of the new oligoclonal preparations in vivo (16.4 IU/100
      micrograms Fab) was comparable to those of the best combinations of hybridoma
      derived human monoclonal antibodies, and far better than those exhibited by the
      polyclonal serum antibodies of the donor (0.29 IU/100 micrograms IgG) or by a
      standard commercial human tetanus immunoglobulin preparation. These data suggest
      that recombinant antibodies may become a safe and effective alternative to human
      plasma-derived immunoglobulins for passive immunization.

PMID- 9634807
TI  - Analyzing the science and ethics of xenografts.

PMID- 9634806
TI  - Removal of sialic acid from a glycoprotein in CHO cell culture supernatant by
      action of an extracellular CHO cell sialidase.
AB  - We have directly tested the hypothesis that Chinese hamster ovary (CHO) cell
      produced glycoproteins are subject to extracellular degradation by a sialidase
      endogenous to the CHO cell line. Factors important to understanding the potential
      for extracellular degradation are addressed including the glycoprotein
      specificity, subcellular source, mechanism of release, and stability of the
      sialidase activity. The extracellular CHO cell sialidase apparently originates
      from the cytosol of the cells, and is released to the cell culture supernatant as
      a result of damage to the cellular membrane. The extracellular sialidase is
      active toward a variety of CHO cell-produced glycoproteins, and can hydrolyze
      sialic acid from the recombinant glycoprotein gp120 in the culture supernatant.
      While measuring the actual degradation of a glycoprotein by extracellular CHO
      cell sialidase can be difficult, data presented here suggest that the level of
      degradation can be estimated indirectly by using a more convenient fluorescent
      substrate, 4-methylumbelliferyl-alpha-D-N-acetylneuraminic acid, to quantify
      sialidase activity. Degradation by sialidase is minimized through addition of the
      sialidase inhibitor 2,3-dehydro-2-deoxy-N-acetylneuraminic acid to the culture
      supernatant. The results in this study suggest additional potential approaches
      for minimizing degradation by sialidase, including isolation of a sialidase
      deficient CHO cell line.

PMID- 9634808
TI  - Human IgA monoclonal antibodies specific for a major ragweed pollen antigen.
AB  - Human hybridoma cell lines secreting IgG specific for the major allergen in the
      pollen of short ragweed, Amb a I, were established from patients who had been
      receiving antigen injections for immunotherapy. Recombinant Ig genes were then
      constructed by cloning the heavy and light chain variable region genes of the
      human hybridoma cell line and joining them to the human alpha or kappa constant
      region genes in mammalian expression vectors. Amb a I-specific IgA was expressed
      in two mouse myeloma cell lines, NS0 and Sp2/0. In both systems, transfected
      alpha and kappa chains were assembled into IgA monomers or into dimers covalently
      linked by the endogenous murine J chains. We propose that recombinant IgA
      monoclonal antibodies specific for airborne allergens may be applied to the
      mucosal surface of the nasal linings or of the lower airway of sensitized
      individuals to inhibit the entry of allergenic molecules across the mucosal
      epithelium and, therefore, to prevent the development of allergic responses.

PMID- 9634809
TI  - Production of monoclonal antibodies using a secretion capture report web.
AB  - We describe a novel method for the production of monoclonal antibodies using a
      secretion capture report web (SCRW). Following HAT selection in bulk culture,
      individual hybridomas are encapsulated in biotinylated agarose drops. Antibody
      secreted by the hybridoma is captured within the agarose drop using an avidin
      bridge and biotinylated anti-mouse immunoglobulin. The secreted antibody is
      detected by a fluorescent reporter which can be either a second anti-mouse
      antibody or an antigen. The binding of the reporter can be quantitated and the
      desired hybridoma directly cloned by flow cytometry. Multiparameter (i.e., two
      color) reporter analysis can also be used to selectively enrich and clone rare
      hybridomas secreting antibodies directed to unique epitopes. The method allows
      the characterization of thousands of clones per second and the isolation of
      hundreds of clones per day.

PMID- 9634810
TI  - Improved mimicry of a foot-and-mouth disease virus antigenic site by a viral
      peptide displayed on beta-galactosidase surface.
AB  - A major antigenic site (site A) of foot-and-mouth disease virus includes multiple
      overlapping epitopes located within the flexible G-H loop of capsid protein VP1.
      We have studied the antigenicity of several recombinant E. coli beta
      galactosidases displaying the site A from a serotype C virus in different surface
      regions of the bacterial enzyme. In each one of the explored insertion sites, the
      recombinant peptide shows different specificity with a set of anti-virus
      monoclonal antibodies directed to site A. In some of them, the inserted stretch
      mimics better than free or haemocyanin-coupled peptide the antigenicity of site A
      in the intact virus. In particular, an insertion within an exposed loop involved
      in the activating interface of beta-galactosidase (amino acids 272 to 287) led to
      a significant improvement of the overall reactivity. Since insertions at this
      site renders proteins enzymatically active, the activating interface could be an
      adequate place for the presentation of foreign antigens in correctly assembled
      beta-galactosidase tetramers. These results also suggest that anti-virus
      antibodies directed against the major antigenic site of FMDV recognize different
      conformations of the G-H loop, which are better reproduced in some of the
      recombinant proteins because of the dissimilar restrictions imposed by each
      particular insertion site.

PMID- 9634811
TI  - How will biotechnology fare in pharma's big plan?

PMID- 9634812
TI  - Genomic sciences and the medicine of tomorrow.

PMID- 9634813
TI  - What's in a name?

PMID- 9634814
TI  - Gene knockout by viral delivery.

PMID- 9634815
TI  - The 2',5' a antiviral system in plants: a dose of mammalian medicine.

PMID- 9634816
TI  - Taking out Tat.

PMID- 9634817
TI  - Trawling for proteins in the post-genome era.

PMID- 9634818
TI  - Residue "switch" revealed in PTH system.

PMID- 9634819
TI  - New treatments for acute stroke.

PMID- 9634820
TI  - The extreme sensitivity of Mycobacterium tuberculosis to the front-line
      antituberculosis drug isoniazid.
AB  - Mycobacterium tuberculosis is a natural mutant in oxyR, a close homolog of the
      central regulator of peroxide stress response in enteric bacteria. Inactivation
      of oxyR is specific for M. tuberculosis and other members of the M. tuberculosis
      complex. This phenomenon appears as a paradox due to the ability of this organism
      to parasitize host macrophages, in which the ingested organisms are likely to be
      exposed to reactive oxygen intermediates. However, the surprising finding that M.
      tuberculosis has multiple deletions, nonsense and frameshift mutations in oxyR
      may help explain the exceptionally high sensitivity of M. tuberculosis to the
      potent antituberculosis agent isoniazid. One of the genes affected by oxyR
      lesions, ahpC (encoding an alkylhydroperoxide reductase) may determine the
      intrinsic sensitivity of mycobacteria to isoniazid.

PMID- 9634821
TI  - Sustained somatic gene inactivation by viral transfer of Cre recombinase.
AB  - Transgenic and knockout mice have proven invaluable tools for analyzing
      physiologically relavant functions of numerous genes. In some cases, however,
      pleiotropic effects that result from a variable requirement for a particular gene
      in different tissues, cell types, or stages of embryonic development may
      complicate the analysis due to a complex phenotype or embryonic lethality. The
      loxP/Cre-mediated recombination system, which allows tissue-specific gene
      targeting in the mouse, can be used to overcome these problems. A limitation of
      current methods is that a mouse carrying a loxP-tagged gene must be crossed with
      a transgenic mouse expressing the Cre recombinase in an appropriate tissue to
      obtain the desired gene rearrangement. We have used recombinant adenovirus
      carrying the Cre recombinase to induce virtually quantitative somatic cell gene
      disruption in the liver. The targeted gene was the multifunctional low-density
      lipoprotein receptor-related protein (LRP), a cell surface receptor for alpha 2
      macroglobulin and other ligands. Transient expression of Cre following adenoviral
      infection produced the predicted gene rearrangement, functionally inactivating
      LRP in the liver. Rearrangement occurred within 6 days after infection and
      remained stable for at least 28 days. The results demonstrate the suitability of
      adenoviral Cre gene transfer to induce long-term, quantitative, and temporally
      controlled gene disruption in the mouse.

PMID- 9634822
TI  - Virus-induced cell death in plants expressing the mammalian 2',5' oligoadenylate
      system.
AB  - The major components of the 2-5A system, responsible for the mammalian interferon
      induced antiviral response, are the 2',5' oligoadenylate synthetase (2-5Aase) and
      2',5' oligoadenylate (2-5A) dependent ribonuclease (RNase L). Transgenic tobacco
      plants expressing these two enzyme activities were produced by crossing the
      transgenic plants expressing RNase L with those expressing 2-5Aase. The double
      transgenic plants showed complete resistance against cucumber mosaic virus (CMV),
      infection with necrotic spots only forming on the virus-inoculated leaf. On the
      other hand, although plants inoculated with potato virus Y (PVY) formed necrotic
      spots on the inoculated leaf and virus amplification could not be detected, all
      plants died within 20 days of inoculation. The transgenic tobacco plants
      expressing either 2-5Aase or RNase L activity showed typical disease symptoms
      with CMV- or PVY-inoculation. These results suggest that the introduced 2-5A
      system is activated in tobacco cells by dsRNA, the replicating intermediates of
      RNA viruses, leading to death of the host cells, which has not been observed in
      mammalian cells.

PMID- 9634823
TI  - Adenovirus targeted to heparan-containing receptors increases its gene delivery
      efficiency to multiple cell types.
AB  - Adenovirus (Ad) is used as a vector for gene delivery in therapies involving
      genetic disease, vascular disease, and cancer. The first step for efficient gene
      transfer is effective virus binding to the target cells. We have found that Ad
      mediated gene delivery to multiple cell types is much less efficient compared to
      epithelial-derived cells. Low gene delivery to nonepithelial cell types was
      directly correlated to a deficiency of the cellular receptor which mediates Ad
      binding. To overcome this inefficiency we constructed a new virus, AdPK, that
      contains a heparin-binding domain that targets the virus to broadly expressed,
      heparan-containing cellular receptors. AdPK delivers genes to multiple cell types
      at markedly higher efficiencies than unmodified Ad. Viruses with enhanced
      attachment characteristics significantly improve gene transfer efficiency and may
      expand the tissues amenable to efficient Ad-mediated gene therapy.

PMID- 9634824
TI  - Targeted gene delivery by tropism-modified adenoviral vectors.
AB  - The utility of adenoviral vectors for gene therapy is currently limited due, in
      part, to the widespread distribution of the cellular receptor for the adenovirus
      fiber that precludes the targeting of specific cell types. In order to develop a
      targeted adenovirus, it is therefore necessary both to ablate endogenous viral
      tropism and to introduce novel tropism. We hypothesized that these two goals
      could be achieved by employing a neutralizing anti-fiber antibody, or antibody
      fragment, chemically conjugated to a cell-specific ligand. To test this concept,
      we chose to target the folate receptor, which is overexpressed on the surface of
      a variety of malignant cells. Therefore, we conjugated folate to the neutralizing
      Fab fragment of an anti-fiber monoclonal antibody. This Fab-folate conjugate was
      complexed with an adenoviral vector carrying the luciferase reporter gene and was
      shown to redirect adenoviral infection of target cells via the folate receptor at
      a high efficiency. Furthermore, when complexed with an adenoviral vector carrying
      the gene for herpes simplex virus thymidine kinase, the Fab-folate conjugate
      mediated the specific killing of cells that overexpress the folate receptor. This
      work thus represents the first demonstration of the retargeting of a recombinant
      adenoviral vector via a non-adenoviral cellular receptor.

PMID- 9634825
TI  - Protein identification by solid phase microextraction-capillary zone
      electrophoresis-microelectrospray-tandem mass spectrometry.
AB  - We describe an analytical system for the rapid identification of proteins by
      correlation of tandem mass spectra with protein sequence databases. The system
      consists of an integrated solid phase microextraction/capillary zone
      electrophoresis peptide separation device that is connected through a
      microelectrospray ion source to a tandem mass spectrometer. The limits of
      detection are 660 amol of sample at a concentration limit of < 33
      amol/microliters for peptide mass measurement, and < 10 fmol of sample, at a
      concentration limit of < 300 amol/microliters for peptide analysis by collision
      induced dissociation. Using this system, we have identified low nanogram amounts
      of yeast proteins separated by high-resolution two-dimensional gel
      electrophoresis.

PMID- 9634826
TI  - The rapid identification of intact microorganisms using mass spectrometry.
AB  - Antibiotic-resistant strains of bacteria continue to emerge, increasing the need
      for their fast and accurate identification. Matrix-assisted laser desorption
      ionization time of flight mass spectrometry (MALDI-TOF-MS), has become a
      prominent technique in biological mass spectrometry. We report the application of
      MALDI-TOF-MS for the identification of intact Gram-negative and Gram-positive
      microorganisms taken directly from culture. Analysis of bacteria from a single
      colony is possible, allowing the screening of mixed cultures. Sample preparation
      is simple and the analysis automated, providing spectra within minutes. The
      spectra obtained allow identification of microorganisms from different genera,
      different species, and from different strains of the same species. The procedure
      provides a unique mass spectral fingerprint of the microorganism, produced from
      desorbed components of the cell wall. Consistent data were obtained from
      subcultures grown for 3-day and 6-day periods, from the same cultures 1 day later
      and from fresh subcultures 2 months later.

PMID- 9634827
TI  - Inactivation of MET10 in brewer's yeast specifically increases SO2 formation
      during beer production.
AB  - Sulfite is widely used as an antioxidant in food production. In beer brewing,
      sulfite has the additional role of stabilizing the flavor by forming adducts with
      aldehydes. Inadequate amounts of sulfite are sometimes produced by brewer's
      yeasts, so means of controlling the sulfite production are desired. In
      Saccharomyces yeasts, MET10 encodes a subunit of sulfite reductase. Partial or
      full elimination of MET10 gene activity in a brewer's yeast resulted in increased
      sulfite accumulation. Beer produced with such yeasts was quite satisfactory and
      showed increased flavor stability.

PMID- 9634828
TI  - Positive selection system to screen for inhibitors of human immunodeficiency
      virus-1 transcription.
AB  - We describe a transcription-based assay system to screen for antiviral drugs in
      vivo. The system consists of two transcription units, a cytomegalovirus promoter
      driving a reporter gene physically linked to an HIV-1 promoter oriented in the
      opposite direction. Based on the arrangement of the transcription units, enhanced
      HIV-1 promoter activity in the presence of the viral transactivating Tat protein
      downregulates reporter gene expression initiated from the CMV promoter.
      Inhibitors of HIV-1 transcription relieve the suppression and are identified by
      an increase in reporter gene expression. This positive selection system allows
      discrimination between drugs that nonspecifically block cellular functions by
      cytotoxicity and molecules that specifically repress HIV-1 promoter activity.

PMID- 9634829
TI  - Genetic engineering of potato for broad-spectrum protection against virus
      infection.
AB  - Transgenic potato plants expressing mutant alleles of PLRV ORF4, the gene for the
      movement protein pr17 of this luteovirus, were generated for broad-range
      protection against virus infection. When tested for protection against infection
      by PLRV, all transgenic lines showed a significant reduction of virus antigen.
      Potato lines accumulating N- or C-terminally extended PLRV pr17 mutant proteins
      were resistant to infection by the unrelated potato viruses PVY and PVX.
      Transgenic lines that did not express protein despite high transcript levels
      failed to exhibit virus resistance.

PMID- 9634830
TI  - Taking the hex off transgenic plant exports.

PMID- 9634831
TI  - Why technology-based regulations don't work.

PMID- 9634832
TI  - Measuring taxol production.

PMID- 9634833
TI  - Taxol supply problem? What problem?

PMID- 9634834
TI  - Gene of the month.

PMID- 9634835
TI  - Genetic tests forge ahead, despite scientific concerns.

PMID- 9634836
TI  - Nobel discovery in combinatorial chemistry.

PMID- 9634837
TI  - US army to investigate "friendly fire" infections of Gulf war veterans.

PMID- 9634838
TI  - Investors, HMOs, policy makers see value in vaccines.

PMID- 9634839
TI  - Double standards in GMP deduplication row.

PMID- 9634840
TI  - Sequence to array: probing the genome's secrets.

PMID- 9634841
TI  - Intracerebral xenografts: Sertoli cells to the rescue?

PMID- 9634842
TI  - Reengineering growth factors "through the looking glass".

PMID- 9634843
TI  - Close encounters of the PNA kind.

PMID- 9634844
TI  - Big news for plant transformation.

PMID- 9634845
TI  - Metabolic engineering: the concept coalesces.

PMID- 9634846
TI  - In vitro models for in vivo drug profiles.

PMID- 9634847
TI  - Biotechnology consortia versus multifirm alliances: paradigm shift at work?

PMID- 9634848
TI  - Bioregios put Germany on the biodevelopment map.

PMID- 9634849
TI  - Scanning of nucleic acids by in vitro amplification: new developments and
      applications.
AB  - Nucleic acids can be characterized using a variety of "fingerprinting" techniques
      usually based on nucleic acid hybridization or enzymatic amplification. The
      scanning of nucleic acids by amplification with arbitrary oligonucleotide primers
      has become popular because it can generate simple-to-complex patterns from
      anonymous DNA or RNA templates without requiring prior knowledge of nucleic acid
      sequence or cloned or characterized probes. Discrete loci are amplified within
      genomic DNA, DNA complementary to mRNA populations (cDNA), cloned DNA fragments,
      and even PCR products. The potential and limitations of the various genome
      scanning techniques, novel improvements, and their recent use in comparative and
      experimental biology applications, including the analysis of plant and bacterial
      genomes are discussed.

PMID- 9634850
TI  - Expression monitoring by hybridization to high-density oligonucleotide arrays.
AB  - The human genome encodes approximately 100,000 different genes, and at least
      partial sequence information for nearly all will be available soon. Sequence
      information alone, however, is insufficient for a full understanding of gene
      function, expression, regulation, and splice-site variation. Because cellular
      processes are governed by the repertoire of expressed genes, and the levels and
      timing of expression, it is important to have experimental tools for the direct
      monitoring of large numbers of mRNAs in parallel. We have developed an approach
      that is based on hybridization to small, high-density arrays containing tens of
      thousands of synthetic oligonucleotides. The arrays are designed based on
      sequence information alone and are synthesized in situ using a combination of
      photolithography and oligonucleotide chemistry. RNAs present at a frequency of
      1:300,000 are unambiguously detected, and detection is quantitative over more
      than three orders of magnitude. This approach provides a way to use directly the
      growing body of sequence information for highly parallel experimental
      investigations. Because of the combinatorial nature of the chemistry and the
      ability to synthesize small arrays containing hundreds of thousands of
      specifically chosen oligonucleotides, the method is readily scalable to the
      simultaneous monitoring of tens of thousands of genes.

PMID- 9634851
TI  - A fiber-optic DNA biosensor microarray for the analysis of gene expression.
AB  - A fiber-optic biosensor array is described for the simultaneous analysis of
      multiple DNA sequences. A bundle of optical fibers was assembled with each fiber
      carrying a different oligonucleotide probe immobilized on its distal end.
      Hybridization of fluorescently labeled complementary oligonucleotides to the
      array was monitored by observing the increase in fluorescence that accompanied
      binding. The approach enables fast (< 10 min) and sensitive (10 nM) detection to
      multiple DNA sequences simultaneously, with the potential for quantitative
      hybridization analysis.

PMID- 9634852
TI  - Cloning differentially expressed mRNAs.
AB  - Differential gene expression occurs in the process of development, maintenance,
      injury, and death of unicellular as well as complex organisms. Differentially
      expressed genes are usually identified by comparing steady-state mRNA
      concentrations. Electronic subtraction (ES), subtractive hybridization (SH), and
      differential display (DD) are methods commonly used for this purpose. A rigorous
      examination has been lacking and therefore quantitative aspects of these methods
      remain speculative. We compare these methods by identifying a total of 58 unique
      differentially expressed mRNAs within the same experimental system (HeLa cells
      treated with interferon-gamma). ES yields digital, reusable data that quantitated
      steady-state mRNA concentrations but only identified abundant mRNAs (seven were
      identified), which represent a small fraction of the total number of
      differentially expressed mRNAs. SH and DD identified abundant and rare mRNAs (33
      and 23 unique mRNAs respectively) with redundancy. The redundancy is mRNA
      abundance-dependent for SH and primer-dependent for DD. We conclude that DD is
      the method of choice because it identifies mRNAs independent of prevalence, uses
      small amounts of RNA, identifies increases and decreases of mRNA steady-state
      levels simultaneously, and has rapid output.

PMID- 9634853
TI  - Testis-derived Sertoli cells survive and provide localized immunoprotection for
      xenografts in rat brain.
AB  - Transplantation of neural tissue into the mammalian central nervous system has
      become an alternative treatment for neurodegenerative disorders such as
      Parkinson's disease. Logistical and ethical problems in the clinical use of human
      fetal neural grafts as a source of dopamine for Parkinson's disease patients has
      hastened a search for successful ways to use animal dopaminergic cells for human
      transplantation. The present study demonstrates that transplanted testis-derived
      Sertoli cells into adult rat brains survive. Furthermore, when cotransplanted
      with bovine adrenal chromaffin cells (xenograft), Sertoli cells produce localized
      immunoprotection, suppress microglial response and allow the bovine cells to
      survive in the rat brain without continuous systemic immunosuppressive drugs.
      These novel features support Sertoli cells as a viable graft source for
      facilitating the use of xenotransplantation for Parkinson's disease and suggest
      their use as facilitators, (i.e., localized immunosuppression) for cell
      transplantation in general.

PMID- 9634854
TI  - Engineering epidermal growth factor for enhanced mitogenic potency.
AB  - Successful use of growth factors in therapeutic and bioprocessing applications
      requires overcoming two attenuation mechanisms: growth factor depletion and
      receptor down-regulation. Current ameliorative strategies use physiologically
      inappropriate high growth-factor concentrations, along with periodic media
      refeeding in vitro and reinjection or controlled-release devices in vivo. We
      demonstrate a new approach derived from understanding how these attenuation
      mechanisms arise from ligand/receptor trafficking processes. Specifically, a
      recombinant epidermal growth factor (EGF) mutant with reduced receptor binding
      affinity is a more potent mitogenic stimulus for fibroblasts than natural EGF or
      transforming growth factor alpha because of its altered trafficking properties.

PMID- 9634855
TI  - Enhancement of strand invasion by oligonucleotides through manipulation of
      backbone charge.
AB  - The ability of DNA oligonucleotides, neutral peptide nucleic acids (PNAS), and
      oligonucleotide conjugates to hybridize to inverted repeat sequences within
      supercoiled double-stranded DNA by Watson-Crick base-pairing is examined. PNAs
      and oligonucleotide conjugates initiate and maintain strand invasion under more
      stringent conditions than do unmodified DNA oligonucleotides. PNAs hybridize
      rapidly and, once bound, hold open a target site allowing oligonucleotides to
      base-pair to the displaced strand under conditions that would otherwise preclude
      hybridization. The ability to manipulate hybridization efficiency through
      different options for the alteration of oligomer charge should have important
      implications for optimizing sequence-specific recognition of DNA.

PMID- 9634856
TI  - Molecular mechanisms of biocatalytic desulfurization of fossil fuels.
AB  - The development of biocatalytic desulfurization of petroleum fractions may allow
      its use in place of conventional hydrodesulfurization (HDS). Dibenzothiophene
      (DBT) is representative of a broad range of sulfur heterocycles found in
      petroleum that are recalcitrant to desulfurization via HDS. Rhodococcus sp.
      strain IGTS8 has the ability to convert DBT to 2-hydroxybiphenyl (HBP) with the
      release of inorganic sulfur. The conversion of DBT to HBP is catalyzed by a
      multienzyme pathway consisting of two monooxygenases and a desulfinase. The final
      reaction catalyzed by the desulfinase appears to be the rate limiting step in the
      pathway. Each of the enzymes has been purified to homogeneity and their kinetic
      and physical properties studied. Neither monooxygenase has a tightly bound
      cofactor and each requires an NADH-FMN oxidoreductase for activity. An NADH-FMN
      oxidoreductase has been purified from Rhodococcus and is a protein of
      approximately 25,000 molecular weight with no apparent sequence homology to any
      other protein in the databases. We describe a unique sulfur acquisition system
      that Rhodococcus uses to obtain sulfur from very stable heterocyclic molecules.

PMID- 9634858
TI  - Open sandwich ELISA: a novel immunoassay based on the interchain interaction of
      antibody variable region.
AB  - We describe an immunoassay that is based on the interchain interaction of
      separated VL and VH chains from a single chain antibody variable region. In the
      presence of antigen, the chains reassociate. VL fragments of anti-hen egg
      lysozyme (HEL) antibody HyHEL-10 were immobilized on microtiter plates. Samples
      were coincubated with an M13-displayed VH chain, and assayed with peroxidase
      labeled anti-M13 antibody. Signal was detected in direct proportion to the amount
      of HEL in the sample. Wide dynamic range with < 15 ng/ml sensitivity was
      attained.

PMID- 9634857
TI  - Transdermal delivery of peptides by iontophoresis.
AB  - Transdermal administration by iontophoresis (enhanced transport via the skin
      using the driving force of an applied electric field) has been successfully
      demonstrated but no formal relationship between peptide sequence/structure and
      efficiency of delivery has been established. There are notable examples, such as
      the lipophilic leutinizing hormone releasing hormone (LHRH) analogs, Nafarelin
      and Leuprolide, that exhibit down-regulation of their own transport across the
      skin under the influence of an iontophoretic current. The hypothesis that this
      phenomenon is due to neutralization of the skin's net negative charge by these
      cationic peptides was examined with LHRH oligopeptides. The impact of these
      compounds on the electroosmotic flow of solvent into the skin, which is induced
      by iontophoresis and which contributes significantly to the electrotransport of
      large, positively charged ions, was examined and quantified. Close juxtaposition
      of cationic and lipophilic residues profoundly inhibited electroosmosis and,
      presumably, peptide flux. The results indicate that the lipophilicity of the
      oligopeptides facilitates van der Waals interactions with hydrophobic patches
      along the transport route, thereby permitting the positively charged oligopeptide
      to interact with carboxylate side chains that give the skin its net negative
      charge at neutral pH. The lipophilic, cationic oligopeptide, therefore, becomes
      anchored in the transport path, neutralizing the original charge of the membrane,
      and completely altering the permselective properties of the skin.

PMID- 9634859
TI  - A clinician looks at the tearfilm.

PMID- 9634860
TI  - Influence of gender, sex steroid hormones, and the hypothalamic-pituitary axis on
      the structure and function of the lacrimal gland.

PMID- 9634861
TI  - Androgen-regulated transcription in the epithelium of the rat lacrimal gland.

PMID- 9634862
TI  - Gene cloning of BM180, a lacrimal gland enriched basement membrane protein with a
      role in stimulated secretion.
AB  - BM180 is a novel basement membrane component with a role in regulated tear
      secretion by lacrimal acinar cells. BM180 bears some sequence similarity to alpha
      gliadin, a plant protein against which antibodies have been reported in patients
      with Sjogren's syndrome. A precedent for plantlike sequence in the mammalian
      genome is provided by selectins, which possess a plant lectinlike domain involved
      in inflammatory cell homing. Cloning the mouse and human BM180 gene will aid
      molecular investigation of lacrimal acinar cell-BM180 interactions and may lead
      to a new molecular understanding of mechanisms contributing to dry eye.

PMID- 9634863
TI  - Sensory denervation leads to deregulated protein synthesis in the lacrimal gland.

PMID- 9634864
TI  - Acinar cell basal-lateral membrane-endomembrane traffic may mediate interactions
      with both T cells and B cells.

PMID- 9634865
TI  - Tissue expression of tear lipocalin in humans.

PMID- 9634866
TI  - The exorbital lacrimal glands of the rat are tensed in situ.

PMID- 9634867
TI  - Aberrant lacrimal gland development in an anophthalmic mutant strain of rat.

PMID- 9634868
TI  - Hormonal influences on Syrian hamster lacrimal gland. Marked repression of a
      major 20 kDa secretory protein by estrogens, androgens, and thyroid hormones.

PMID- 9634869
TI  - Androgen support of lacrimal gland function in the female rabbit.

PMID- 9634871
TI  - Dinucleotide repeat polymorphism near the tear lipocalin gene.

PMID- 9634870
TI  - Identification and hormonal control of sex steroid receptors in the eye.

PMID- 9634872
TI  - Studies of ligand binding and CD analysis with apo- and holo-tear lipocalins.

PMID- 9634874
TI  - Calcium signalling in lacrimal acinar cells.

PMID- 9634873
TI  - Signal transduction pathways activated by cholinergic and alpha 1-adrenergic
      agonists in the lacrimal gland.

PMID- 9634875
TI  - Voltage- and Ca(2+)-dependent chloride current activated by hyposmotic and
      hyperosmotic stress in rabbit superior lacrimal acinar cells.

PMID- 9634876
TI  - G protein coupling of receptor activation to lacrimal secretion.

PMID- 9634877
TI  - Microtubules and intracellular traffic of secretory proteins in rat extraorbital
      lacrimal glands.

PMID- 9634878
TI  - Effects of neuropeptides on serotonin release and protein and peroxidase
      secretion in the isolated rat lacrimal gland.

PMID- 9634879
TI  - Analysis of phosphodiesterase isoenzymes in the ocular glands of the rabbit.

PMID- 9634880
TI  - Immunohistochemistry and secretory effects of leucine enkephalin in the isolated
      pig lacrimal gland.

PMID- 9634881
TI  - Interaction between vasoactive intestinal polypeptide (VIP) and neuropeptide Y
      (NPY) in the isolated rat lacrimal gland.

PMID- 9634882
TI  - Identification and cellular localization of the components of the VIP signaling
      pathway in the lacrimal gland.

PMID- 9634883
TI  - Kinesin activation drives the retrieval of secretory membranes following
      secretion in rabbit lacrimal acinar cells.

PMID- 9634884
TI  - Protein kinase C isoforms differentially control lacrimal gland functions.

PMID- 9634885
TI  - Role of protein kinases in regulation of apical secretion and basal-lateral
      membrane recycling traffic in reconstituted rabbit lacrimal gland acini.

PMID- 9634886
TI  - Brefeldin A detoxification in rat extraorbital lacrimal glands.

PMID- 9634887
TI  - Identification and characterization of G proteins in the mammalian lacrimal
      gland.

PMID- 9634888
TI  - Inward-rectifying potassium channels in the rabbit superior lacrimal gland.

PMID- 9634889
TI  - Electrophysiological evidence for reduced water flow from lacrimal gland acinar
      epithelium of NZB/NFW F1 mice.

PMID- 9634890
TI  - Cellular origin of mucins of the ocular surface tear film.
AB  - In summary, we have demonstrated that the ocular surface epithelia express at
      least three mucin genes. We suggest that the gel-forming mucin MUC5AC is a major
      mucin forming the mucus gel of the tear film. We further suggest that MUC1
      facilitates the spread of the MUC5-containing mucus on the ocular surface and,
      along with the mucus gel, prevents cell and debris adhesion to the ocular
      surface. The function of MUC4 at the ocular surface remains to be elucidated.

PMID- 9634891
TI  - Soluble mucin and the physical properties of tears.

PMID- 9634892
TI  - Characterization and origin of major high-molecular-weight tear
      sialoglycoproteins.

PMID- 9634893
TI  - Detection and quantification of conjunctival mucins.

PMID- 9634894
TI  - Mucous contribution to rat tear-film thickness measured with a microelectrode
      technique.

PMID- 9634895
TI  - Structural analysis of secreted ocular mucins in canine dry eye.

PMID- 9634896
TI  - Corneal epithelial tight junctions and the localization of surface mucin.

PMID- 9634897
TI  - Breakup and dewetting of the corneal mucus layer. An update.

PMID- 9634898
TI  - The meibomian glands and tear film lipids. Structure, function, and control.
AB  - Meibomian gland disease--and, in particular, obstructive meibomian gland disease-
      makes an important contribution to ocular surface disease, in the form of
      meibomian keratoconjunctivitis. With improved methods for the study of meibomian
      oil composition and function, we are moving closer to the possibility of
      distinguishing the contribution of meibomian deficiency, as opposed to
      inflammatory events, to this disorder. More importantly, where aqueous tear
      deficiency and meibomian gland disease coincide in patients with dry eye, we are
      closer to the possibility of distinguishing their relative contributions to the
      dry eye state. This has implications for future therapies.

PMID- 9634899
TI  - Tear film interferometry as a diagnostic tool for evaluating normal and dry-eye
      tear film.

PMID- 9634900
TI  - Human and rabbit lipid layer and interference pattern observations.

PMID- 9634901
TI  - Abnormal lipid layers. Observation, differential diagnosis, and classification.

PMID- 9634902
TI  - Association of tear lipid layer interference patterns with superficial punctate
      keratopathy.

PMID- 9634903
TI  - Meibomian secretions in chronic blepharitis.

PMID- 9634904
TI  - Androgen regulation of the meibomian gland.

PMID- 9634905
TI  - Delivery of meibomian oil using the Clinical Meibometer.

PMID- 9634906
TI  - Volume of the human and rabbit meibomian gland system.

PMID- 9634907
TI  - Effect of meibomian gland occlusion on tear film lipid layer thickness.

PMID- 9634908
TI  - Meibomian gland lipids, evaporation, and tear film stability.

PMID- 9634909
TI  - Surface-chemical pathways of the tear film breakup. Does corneal mucus have a
      role?

PMID- 9634910
TI  - The biophysical role in tear regulation.

PMID- 9634911
TI  - Longitudinal analysis of precorneal tear film rupture patterns.

PMID- 9634912
TI  - The role of tear proteins in tear film stability in the dry eye patient and in
      the rabbit.

PMID- 9634913
TI  - Relationship between pre-ocular tear film structure and stability.

PMID- 9634914
TI  - Association of precorneal and preconjunctival tear film.

PMID- 9634915
TI  - Age and gender effects on the normal tear film.

PMID- 9634916
TI  - The kinetics of lid motion and its effects on the tear film.

PMID- 9634917
TI  - Hydrodynamics of meniscus-induced thinning of the tear film.

PMID- 9634918
TI  - Computer-assisted calculation of exposed area of the human eye.

PMID- 9634919
TI  - Cytokines. An overview.

PMID- 9634921
TI  - Apoptosis in the lacrimal gland and conjunctiva of dry eye dogs.

PMID- 9634920
TI  - Gender- and androgen-related impact on the expression of proto-oncogenes and
      apoptotic factors in lacrimal and salivary glands of mouse models of Sjogren's
      syndrome.

PMID- 9634922
TI  - Cytokines and tear function in ocular surface disease.
AB  - In summary, tear EGF levels correlate most strongly with tear production in
      normals, and it is likely that some form of homeostatic mechanism exists to
      provide a constant supply to the ocular surface. Commercial ELISA kits appear to
      measure EGF in tears with good consistency and may be useful in the future to
      improve comparability of data from different studies. In addition, in ocular
      rosacea, which mimics keratoconjunctivitis sicca in a number of respects, there
      is a differential increase in the level of the inflammatory cytokine IL-1 alpha
      in the tear fluid. Much of this elevation appears to be the result of reduced
      tear turnover, which may form an important positive feedback mechanism
      encouraging tear stagnation and the perpetuation of ocular surface inflammation.

PMID- 9634924
TI  - Molecular basis and role of differential cytokine production in T helper cell
      subsets in immunologic disease.

PMID- 9634923
TI  - Chemokine production in conjunctival epithelial cells.

PMID- 9634925
TI  - Presence and testosterone influence on the levels of anti- and pro-inflammatory
      cytokines in lacrimal tissues of a mouse model of Sjogren's syndrome.

PMID- 9634927
TI  - Do cytokines have a role in the regulation of lacrimal gland acinar cell ion
      transport and protein secretion?
AB  - The present study explored the potential involvement of cytokines (IL-1 alpha, IL
      1 beta, IL-6, and IFN-gamma) in the regulation of basic physiological processes
      carried out by lacrimal acinar cells. Overall, evidence gathered supports the
      hypothesis that cytokines may be involved in the regulation of lacrimal secretory
      processes. When combined with earlier studies, these data suggest that acute
      treatment (i.e., 20 min) of acinar cells with cytokines does not significantly
      impact either basal or carbachol-stimulated ion transport or protein secretion.
      However, chronic treatment of cultured acinar cells with cytokines does appear,
      in some instances, to influence these cell functions. For example, 24 h treatment
      of acinar cells with IL-6 or IFN-gamma did not alter basal or carbachol
      stimulated protein (beta-hexosaminidase) secretion, whereas a combination of IL-1
      alpha and IL-1 beta decreased carbachol-stimulated beta-hexosaminidase secretion
      by 80%. The mechanism behind this effect is unknown, but it appears to stem from
      an increase in the basal secretion rather than a decrease in the stimulated
      secretion. Future studies will attempt to identify the mechanism behind the
      actions of IL-1 alpha and IL-1 beta, in addition to testing other pertinent
      cytokines (e.g., TNF-alpha, TGF-beta). The study of cytokine involvement in the
      regulation of lacrimal acinar cell physiology has received relatively little
      attention. Thus, substantial gaps remain concerning the identity of cytokines,
      their source(s) and interplay, receptor distribution, second messenger
      involvement, and ultimate influence over the secretion of aqueous tears.

PMID- 9634926
TI  - Infiltrating lymphocyte populations and cytokine production in the salivary and
      lacrimal glands of autoimmune NOD mice.

PMID- 9634928
TI  - The rat exorbital lacrimal gland as a site of synthesis of EGF-like growth
      factors.

PMID- 9634929
TI  - The distribution of FGF-2 and TGF-beta within the lacrimal gland of rabbits.

PMID- 9634931
TI  - Time course of apoptosis in lacrimal gland after rabbit ovariectomy.

PMID- 9634930
TI  - Tear fluid changes after photorefractive keratectomy.

PMID- 9634932
TI  - Co-expression of bcl-2 and CD44s in basal layers of human ocular surface
      epithelia.

PMID- 9634933
TI  - Alterations of ocular surface gene expression in Sjogren's syndrome.
AB  - We have demonstrated that conjunctival epithelium of SS patients displays
      increased numbers of S-phase cells compared with non-dry eye controls. Moreover,
      in SS patients, these S-phase cells are distributed throughout all strata of the
      epithelium. The expression of MUC-1, a cell surface marker indicative of
      terminally differentiated epithelium, is localized to the conjunctival epithelial
      surface in SS and control patients. However, MUC-1 surface immunoreactivity
      appears to be reduced in SS epithelium, suggesting disruption of normal
      epithelial differentiation. A MUC-1 epitope exposed by pretreatment with
      neuraminidase is expressed in the basal and suprabasal layers of both patient
      populations. This antigen likely represents nascent, partially processed MUC-1(6)
      and may serve as a marker of the preterminally differentiated epithelial
      phenotype. Messenger RNA encoding several different inflammatory cytokines,
      including TNF-alpha, IL-1 alpha and beta, IL-6, IL-8, IL-10, and TGF-beta 1, is
      expressed at elevated levels within the conjunctival epithelium of SS patients
      compared with non-dry eye controls. Based on these observations, we have
      formulated a model to explain the ocular surface pathology of Sjogren's syndrome.
      We hypothesize that mechanical abrasion secondary to aqueous tear deficiency
      creates an inflammatory environment where conjunctival epithelial cells and
      lymphocytes are stimulated to produce and secrete various cytokines (i.e., IL-1,
      TNF-alpha, IL-6, IL-8, etc.) into the tear film. Elevated cytokine levels within
      the tear film, perhaps combined with reduced concentrations of essential lacrimal
      gland-derived factors (i.e., EGF, retinol), create an environment in which
      terminal differentiation of the ocular surface epithelium is impaired. As a
      consequence, the epithelium becomes hyperplastic, displaying increased mitotic
      activity, and loses the ability to express mature protective surface molecules
      including the membrane-bound mucin, MUC-1. This would imply that anti
      inflammatory medications (i.e., corticosteroids or cyclosporine) that suppress
      the inflammatory component of this cascade may ameliorate the ocular surface
      disease and discomfort experienced by SS patients.

PMID- 9634934
TI  - Growth factor interaction with contact lenses: evidence for and possible effects
      of storage of basic FGF in contact lenses. Preliminary results.

PMID- 9634935
TI  - Neural, endocrine, and immune system interactions. Relevance for health and
      disease.

PMID- 9634936
TI  - Inductive sites for rat tear IgA antibody responses.

PMID- 9634937
TI  - Anatomy of mammalian conjunctival lymphoepithelium.
AB  - Ocular surface immune mechanisms are subservient to the fine function of the eye.
      A clear cornea with a smooth, well-lubricated facade is prerequisite to lucid
      vision. Hence, corneal inflammation and post-inflammatory scarring are
      intolerable, and the cornea contains a minimum of lymphoid elements. Although
      conjunctival dysfunction and consequent tear film deficiency can malign the
      corneal surface, conjunctival inflammation is tolerated to a considerable degree.
      In contrast to the human cornea, human conjunctiva contains an abundance of
      lymphoid tissue. Certain aspects of human conjunctival immunology elicit little
      debate. Langerhans cells are abundant in conjunctival epithelium. Isolated CD8+
      suppressor/cytotoxic T cells predominate in conjunctival epithelium, while T
      cells in the substantia propria distribute equally between CD4+ T helper cells
      and CD8+ cells. Yet the presence of plasma cells in human conjunctiva, the
      expression of secretory component by human conjunctival epithelium, and the
      function of human conjunctival lymphoid follicles are in dispute. Confusion may
      derive in part from the use of inappropriate animal models; rodent conjunctiva
      does not appear to be a worthy facsimile for human conjunctiva. Discrepancies
      between different human studies likely result from variance in subject age,
      biopsy site and extent, histologic or histochemical technique, and perhaps the
      degree of inflammation present at the time of biopsy. Careful immunohistochemical
      and in situ molecular assays on well-defined loci within the conjunctiva of
      comparable human subjects may resolve such questions in the future. Organized
      mucosa-associated lymphoid tissue is rigorously defined as mucosal lymphoid
      follicles with an ultrastructurally distinct overlying lymphoepithelium. Based on
      available evidence, the epithelium overlying mammalian conjunctival lymphoid
      follicles does not contain distinct M cells. Whether zonal differences in
      morphology reflect real differences in the capacity to sample tear film antigens
      for presentation to the mucosal immune system remains to be established.

PMID- 9634938
TI  - Binding of a cytopathic or an invasive strain of P. aeruginosa to cytoskeletal,
      basement membrane, or matrix proteins of wounded cornea is similar and does not
      rely on interaction with actin filaments.

PMID- 9634939
TI  - Secretory IgA responses on the human ocular surface.

PMID- 9634940
TI  - A method to study induction of autoimmunity in vitro: co-culture of lacrimal
      cells and autologous immune system cells.
AB  - Co-culturing autologous lacrimal gland cells and immune system cells can lead to
      spleen cell proliferation with a time course similar to that for proliferation in
      a typical heterologous MLR. Although these results are consistent with the
      hypothesis that lacrimal acinar cells are a source of antigen, and may or may not
      serve in part as an APC, future studies of this preparation are required to test
      these hypotheses. We are unaware of reports demonstrating that co-culturing
      control epithelial tissue and autologous splenic lymphocytes from apparently
      healthy animals leads to lymphocytic proliferation. Our results suggest that the
      appropriate co-culture of tissues and immune cells from healthy animals, perhaps
      such as detailed above, should help identify mechanisms contributing to the
      induction of autoimmune disease. Knowledge regarding such mechanisms should help
      efforts to prevent such disease, and perhaps reverse it.

PMID- 9634941
TI  - Rat lacrimal glands contain activated and resting mature T cells, recent thymic
      emigrants, and possibly extrathymic populations.

PMID- 9634942
TI  - Immunohistochemical examination of lacrimal gland tissue from patients with
      ocular sarcoidosis.

PMID- 9634943
TI  - Immunoglobulin levels in the tears of patients with corneal grafts and transplant
      rejection.

PMID- 9634944
TI  - Tear fluid influence on the ocular surface.

PMID- 9634945
TI  - Effects of lacrimal gland removal on squirrel monkey cornea.

PMID- 9634946
TI  - Lacrimal gland growth factors and receptors: lacrimal fibroblastic cells are a
      source of tear HGF.

PMID- 9634947
TI  - Clusterin may be essential for maintaining ocular surface epithelium as a non
      keratinizing epithelium.

PMID- 9634948
TI  - Effects of chronic hypertonic stress on regulatory volume increase and Na-K-2Cl
      cotransporter expression in cultured corneal epithelial cells.

PMID- 9634949
TI  - A unified theory of the role of the ocular surface in dry eye.
AB  - It is our belief that the pathology of dry eye occurs when systemic androgen
      levels fall below the threshold necessary for support of secretory function and
      generation of an anti-inflammatory environment (Fig. 3). When this occurs, both
      the lacrimal gland and the ocular surface become irritated and inflamed, and they
      secrete cytokines that interfere with the normal neural connections that drive
      the tearing reflex. This leaves the lacrimal gland in an isolated condition,
      perhaps exacerbating atrophic alterations of the glandular tissue. These changes
      allow for antigen presentation at the surface of the lacrimal acinar cells and
      increase lymphocytic infiltration of the gland. A similar series of events may be
      occurring on the ocular surface. From this hypothesis we conclude: 1. The ocular
      surface, lacrimal gland, and interconnecting innervation act as an integrated
      servo-mechanism. 2. Once the lacrimal gland loses its androgen support, it is
      subject to immune/neurally mediated dysfunction. 3. The ocular surface is an
      appropriate target for dry eye therapeutics.

PMID- 9634950
TI  - Human tear film components bind Pseudomonas aeruginosa.

PMID- 9634951
TI  - Small-volume analysis of rabbit tears and effects of a corneal wound on tear
      protein spectra.

PMID- 9634952
TI  - 31-27 kDa caseinolytic protease in human tears.

PMID- 9634953
TI  - Tear protein levels following punctal plugging.

PMID- 9634954
TI  - Characterization of cells shed from the ocular surface in normal eyes.

PMID- 9634955
TI  - Healing effect of sodium-sucrose-octasulfate and EGF on epithelial corneal
      abrasions in rabbits.

PMID- 9634956
TI  - A novel approach to resolve cellular volume responses to an anisotonic challenge.

PMID- 9634957
TI  - Classification of artificial tears. I: Composition and properties.

PMID- 9634958
TI  - Classification of artificial tears. II: Additives and commercial formulas.

PMID- 9634959
TI  - The ocular surface, the tear film, and the wettability of contact lenses.

PMID- 9634960
TI  - Conjunctival permeability and ultrastructure. Effects of benzalkonium chloride
      and artificial tears.

PMID- 9634961
TI  - Preservative effect on epithelial barrier function measured with a novel
      technique.

PMID- 9634962
TI  - Video biomicroscopy of the tear film.

PMID- 9634963
TI  - Patient-dependent and material-dependent factors in contact lens deposition
      processes.

PMID- 9634964
TI  - Effectiveness of BION tears, Cellufresh, Aquasite, and Refresh Plus for moderate
      to severe dry eye.

PMID- 9634965
TI  - Ocular residence time of carboxymethylcellulose solutions.

PMID- 9634966
TI  - Vitronectin adsorption in contact lens surfaces during wear. Locus and
      significance.

PMID- 9634967
TI  - Effect of tears and tear residues on worn etafilcon and polymacon disposable
      contact lenses on the adhesion of Pseudomonas aeruginosa.

PMID- 9634968
TI  - Hyaluronan in dry eye and contact lens wearers.

PMID- 9634969
TI  - Epidemiology and classification of dry eye.

PMID- 9634970
TI  - CANDEES. The Canadian Dry Eye Epidemiology Study.

PMID- 9634971
TI  - Sensitivity and specificity of a screening questionnaire for dry eye.
AB  - We developed a Dry Eye Screening Questionnaire for the Dry Eye Epidemiology
      Projects (DEEP), a proposed large epidemiologic study. All persons who screen
      positive and a small sample of those who screen negative are to be invited for a
      diagnostic examination. Containing 19 questions, of which only 14 were used in
      the analysis, the questionnaire takes only a few minutes to administer on the
      telephone. To construct a discriminator function and thus a ROC curve, we used
      stepwise multiple regression on screening responses from a clinic series of 77
      cases and 79 controls. Stepwise regression may incorporate into the predictor
      equation variables whose relation to the predicted is only accidental. Further,
      misclassification rates are underestimated by the resubstitution method, in which
      the proportion misclassified is obtained from the same dataset in which the
      discriminator function was fitted. To counter these problems, we randomly divided
      the data in half. We chose as predictors only those variables (Dry and Irritated)
      selected by stepwise regression in both data halves. We estimated unbiased
      misclassification rates using the unbiased test set method, in which the
      discriminator is fitted in one data half, and misclassification rates are
      calculated in the other half. Comparison of ROC curves arising from
      resubstitution and test set estimates indicates that resubstitution bias in
      misclassification rate estimation is negligible in our data. A resubstitution
      estimate made on the entire data is thus preferred. The resulting
      sensitivity/specificity values are reasonably high (e.g., 60%/94%), suggesting
      that the questionnaire will be a useful screening tool in the DEEP study. A
      second discriminator using the sum of all 14 responses is similar in its
      misclassification characteristics to the first discriminator. A second
      potentially significant error, arising from applying results from a clinical
      series to a general population, will be investigated as survey results in DEEP
      become available.

PMID- 9634972
TI  - Use of a questionnaire for the diagnosis of tear film-related ocular surface
      disease.

PMID- 9634973
TI  - Importance of conjunctival epithelial evaluation in the diagnostic
      differentiation of dry eye from drug-induced epithelial keratopathy.

PMID- 9634974
TI  - The size of corneal epithelial cells collected by contact lens cytology from dry
      eyes.

PMID- 9634975
TI  - Optimum dry eye classification using questionnaire responses.

PMID- 9634976
TI  - Diagnostic value of tear film abnormalities in a new syndrome affecting the
      neuroendocrine and immune systems.

PMID- 9634977
TI  - Low-tech detection of tear film-related diseases of the ocular surface.

PMID- 9634978
TI  - Using LIPCOF (lid-parallel conjunctival fold) for assessing the degree of dry
      eye, it is essential to observe the exact position of that specific fold.

PMID- 9634979
TI  - Use of the Tearscope Plus and attachments in the routine examination of the
      marginal dry eye contact lens patient.

PMID- 9634980
TI  - Evaluation of Schirmer tests by two types of tear clearance tests.

PMID- 9634981
TI  - Fluorescein dye concentration as a factor in tear film fluorescence.

PMID- 9634982
TI  - A new method for measuring human basic tear fluid osmolality.

PMID- 9634983
TI  - Micropachometric quantification of tear assessment tests.
AB  - After reviewing the results of available methods for defining the dry eye with an
      exact assessment of severity, we found that micropachometry was the most
      sensitive. The following is a ranking of the other tests according to usefulness:
      Tear resistance, Schirmer, and BUT. Rose bengal stained eyes were usually
      decompensated; the meniscus test's primary use was as an "all or nothing"
      indicator, but recording the widths of extant menisci were unproductive.

PMID- 9634984
TI  - Use of corneal thickness changes to compare the efficacy of conventional eye
      drops with supracutaneous treatment of dry eye.

PMID- 9634985
TI  - Sjogren's syndrome. Pathogenesis and new approaches to therapy.

PMID- 9634986
TI  - Reflex tearing in dry eye not associated with Sjogren's syndrome.

PMID- 9634987
TI  - Cytokine mRNA expression in labial salivary glands and cytokine secretion in
      parotid saliva in Sjogren's syndrome.

PMID- 9634988
TI  - Age-related decrease in innervation density of the lacrimal gland in mouse models
      of Sjogren's syndrome.

PMID- 9634989
TI  - Aberrant expression and potential function for parotid secretory protein (PSP) in
      the NOD (non-obese diabetic) mouse.

PMID- 9634990
TI  - Survey of canine tear deficiency in veterinary practice.

PMID- 9634991
TI  - Lacrimation and salivation are not related to lymphocytic infiltration in
      lacrimal and salivary glands in MRL lpr/lpr mice.

PMID- 9634992
TI  - The Sjogren syndrome and tear function profile.

PMID- 9634993
TI  - Cytokines may prove useful in the treatment of Sjogrens syndrome (SS) dry eye.

PMID- 9634994
TI  - The now and future therapy of the non-Sjogren's dry eye.

PMID- 9634995
TI  - Dry eye treatment with eye drops that stimulate mucin production.

PMID- 9634996
TI  - A dose-ranging clinical trial to assess the safety and efficacy of cyclosporine
      ophthalmic emulsion in patients with keratoconjunctivitis sicca. The Cyclosporine
      Study Group.

PMID- 9634997
TI  - Oral pilocarpine for symptomatic relief of dry mouth and dry eyes in patients
      with Sjogrens syndrome.

PMID- 9634998
TI  - Oral pilocarpine for symptomatic relief of keratoconjunctivitis sicca in patients
      with Sjogren's syndrome. The MGI PHARMA Sjogren's Syndrome Study Group.

PMID- 9634999
TI  - Supracutaneous treatment of dry eye patients with calcium carbonate.

PMID- 9635000
TI  - Preclinical safety studies of cyclosporine ophthalmic emulsion.

PMID- 9635001
TI  - Conjunctival impression cytology from dogs with keratoconjunctivitis sicca. Pre-
      and post-treatment with topical cyclosporine.

PMID- 9635002
TI  - Cyclosporine distribution into the conjunctiva, cornea, lacrimal gland, and
      systemic blood following topical dosing of cyclosporine to rabbit, dog, and human
      eyes.

PMID- 9635003
TI  - Estrogen therapy in keratoconjunctivitis sicca.

PMID- 9635004
TI  - Dry eye treatment with acupuncture. A prospective, randomized, double-masked
      study.

PMID- 9635005
TI  - Punctal occlusion for the treatment of dry eye.

PMID- 9635006
TI  - Keratoprosthesis in pemphigoid and Stevens-Johnson syndrome.
AB  - Keratoprosthesis was implanted in 17 eyes with ocular pemphigoid and 7 eyes with
      Stevens-Johnson syndrome and followed for 6 months to 6 years. Visual outcomes
      and complications were compared. Pemphigoid was found to have a much better
      prognosis than did Stevens-Johnson syndrome. Keratoprosthesis is now firmly
      indicated in elderly pemphigoid patients whose vision in both eyes has become
      reduced to hand movements or less due to a corneal opacity.

PMID- 9635007
TI  - Portable device for programmable, automatic, or on-demand delivery of artificial
      tears.

PMID- 9635008
TI  - Hypotaurine oxidation: an HPLC-mass approach.

PMID- 9635009
TI  - In vitro evaluation of hypotaurine activity on oxidized LDL.

PMID- 9635010
TI  - Hypotaurine protection on cell damage by H2O2 and on protein oxidation by Cu+2
      and H2O2.

PMID- 9635011
TI  - Cysteine sulfinate decarboxylase (CSD): molecular cloning, sequence and genomic
      expression in brain.

PMID- 9635012
TI  - Effect of taurine and guanidinoethane sulfonate on glutathione metabolism in the
      rat.

PMID- 9635013
TI  - Determination of cysteinyl-containing peptides and associated enzyme activities
      in rat tissues by reverse phase HPLC.

PMID- 9635014
TI  - The effects of aging on taurine content and biosynthesis in different strains of
      rats.

PMID- 9635015
TI  - Taurine levels and localization in pancreatic islets.

PMID- 9635016
TI  - Pyrrolizidine alkaloid-induced depletion of taurine from rat liver in vivo and in
      vitro.

PMID- 9635017
TI  - Effects of taurine in precision-cut liver slices exposed to the pyrrolizidine
      alkaloid retrorsine.

PMID- 9635018
TI  - Effect of taurine on biliary metabolites of glutathione in liver perfused with
      the pyrrolizidine alkaloid, monocrotaline.

PMID- 9635019
TI  - Antagonism by taurine on the ruthenium red-induced and 6-hydroxydopamine plus 1
      methyl-4-phenylpyridinium-induced Ca2+ release from rat liver mitochondria.

PMID- 9635020
TI  - Effect of taurine supplementation on the lipid peroxide formation and the
      activities of glutathione-related enzymes in the liver and islet of type I and II
      diabetic model mice.
AB  - Effects of taurine supplementation on lipid peroxide formation and the activities
      of glutathione (GSH) dependent enzymes in diabetic model mice were investigated.
      Type I diabetes mellitus was induced by injecting alloxan to ICR mice while type
      II diabetes mellitus was produced by high calorie diet feeding to genetically
      hyperglycemic KK mice. Taurine was given in drinking water at the level of 5%
      (w/v) for seven days. The malondialdehyde (MDA) levels of liver and the islets of
      type I diabetes were significantly increased compared to the control group but
      the levels were significantly decreased by taurine supplementation. In the type
      II diabetic model, the concentrations of MDA were not changed by taurine
      treatment. The activity of hepatic and islet GSH-peroxidase (GPX) was increased
      in the type I diabetic group, but in type II animals it was decreased. Hepatic
      GPX activity of both type I and II diabetics was not altered by taurine
      supplementation but was increased in the islets of the type II animals. No effect
      on the activity of GSH S-transferase (GST) was observed in both types of diabetes
      (I and II) following taurine supplementation. These results suggest that taurine
      supplementation protects type I diabetic mice from lipid peroxide formation.

PMID- 9635022
TI  - Effect of taurine on excitation-contraction coupling of extensor digitorum longus
      muscle of dystrophic mdx mouse.

PMID- 9635021
TI  - Taurine protects the liver against lipid peroxidation and membrane disintegration
      during rat hepatocarcinogenesis.
AB  - The purpose of this study was to determine the effects of taurine supplementation
      on both hepatic morphological changes and the extent of hepatic lipid
      peroxidation and membrane disintegration during rat hepatocarcinogenesis. Sprague
      Dawley rats were fed high fat diets containing 15% corn oil and were maintained
      on drinking water with or without 1% taurine. Two weeks after the appropriate
      feeding regimen, hepatocarcinogenesis was induced by a modification of the Solt
      and Farber method. This involved a 8 week protocol, including diethylnitrosamine
      initiation, 3 weeks of 2-acetylaminofluorene feeding and finally a 70% partial
      hepatectomy. Morphological changes of the hepatocyte were observed by
      transmission electron microscopy (TEM). Hepatocytes of the carcinogen-treated rat
      not exposed to taurine contained normal nuclei, but the endoplasmic reticulum
      (ER) and the mitochondria (Mi) were almost destroyed. By contrast, although the
      hepatocytes from the taurine supplemented group contained some irregular contour
      nuclei, the ER and Mi were normal. In the carcinogen-treated groups, lipid
      peroxidation was decreased because of the activation of several detoxifying
      enzymes. Glutathione S-transferase (GST) activity increased in the carcinogen
      treated groups but less so in the group supplemented with taurine before
      treatment with the carcinogen. In the group supplemented with taurine prior to
      treatment with the carcinogen, glutathione peroxidase (GPx) activity was higher
      than in the carcinogen-treated group lacking taurine exposure. Consistent with
      the severe destruction to the membrane in the carcinogen-treated rats, hepatic
      glucose-6-phosphatase (G6Pase) activity, an index of membrane stability, was also
      decreased. However, both the fall in G6Pase activity and the degree of membrane
      damage was reduced in the carcinogen-treated animals receiving oral taurine.
      These results suggest that taurine appears to inhibit lipid peroxidation, to
      alter the activity of the defense enzymes and to protect the liver against
      membrane disintegration during rat hepatocarcinogenesis.

PMID- 9635023
TI  - Cardiac actions of taurine as a modulator of the ion channels.
AB  - During ischemia, hypoxia and cardiac failure, the heart undergoes several adverse
      changes, including a reduction in taurine (2-aminoethanesulfonic acid). Oral
      administration of taurine under these disease conditions would be expected to act
      like a mild cardiac glycoside. Taurine would exert improvement in the
      accumulation of [Na]i and the loss of alpha-amino acids. Nonetheless, when
      intracellular taurine content is raised, there would be the benefit of increased
      Ca2+ release from the sarcoplasmic reticulum and increased Ca2+ sensitivity of
      the contractile proteins, as well as possible changes in the action potential
      associated with the actions of taurine on ion channels. In fact, intracellular
      application of taurine produces the opposite actions to extracellularly
      administration of the amino acid. From our previous experiments, the
      electrophysiological actions of taurine on cardiac muscle cells include the
      following. (a) Prolongation of action potential duration (APD) at high [Ca]i and
      shortening of APD at low [Ca]i. In multicellular preparations, however, taurine
      did not always prevent [Ca]o-induced effects. (b) Stimulation of spontaneous
      activity at low intracellular and extracellular Ca2+ concentrations ([Ca]i and
      [Ca]o), and vice versa. (c) Inhibition of the L-type Ca2+ current (ICa(L)) at
      high [Ca]i, and vice versa. (d) Enhancement of the T-type Ca2+ current (ICa(T)).
      (e) Inhibition of fast Na+ current (INa). (f) Enhancement of TTX-insensitive slow
      Na+ current. (g) Inhibition of delayed rectifier K+ current (IKrec) at high
      [Ca]i, and vice versa. (h) Enhancement of the transient outward current (Ito).
      (i) Inhibition of the ATP-sensitive K+ current (IK(ATP)). Since taurine acts on
      so many ion channels and transporters, it is clearly non-specific. Although it is
      very difficult to understand the diversity of taurine's actions, it is possible
      that taurine can exert its potent cardioprotective actions under the conditions
      of low [Ca]i, as well as Ca2+ overload. Thus, although taurine-induced modulation
      of ion channels located on the cardiac cell membrane is complex, the multiple
      effects may combine to yield useful therapeutic results.

PMID- 9635024
TI  - Taurine improves angiotensin II-induced hypertrophy of cultured neonatal rat
      heart cells.
AB  - The effect of taurine on angiotensin II-induced hypertrophy of cultured neonatal
      rat heart cells (myocytes and nonmyocytes) was examined. Angiotensin II (1-100
      nM) alone caused an increase in the rate of protein synthesis and the surface
      area of myocytes without altering the rate of DNA synthesis or cell number. It
      also mediated an increase in DNA synthesis and in cell number of nonmyocytes.
      Exposure of the cells to taurine (20 mM) in the absence of angiotensin II had no
      effect on either hyperplastic growth or hypertrophy of the two types of cultured
      cardiac cells. However, myocytes pretreated with 20 mM taurine exhibited reduced
      responsiveness to angiotensin II. Following a 24 hr pretreatment with 20 mM
      taurine, the stimulation in protein synthesis by angiotensin II (1 nM) was
      significantly suppressed. Similarly, taurine treatment of nonmyocytes reduced the
      degree of angiotensin II-induced promotion of hyperplastic growth (DNA synthesis
      and cell number). Finally, taurine partially prevented the rise in [Ca2+]i
      mediated by angiotensin II in cardiac cells. The present results indicate that
      taurine is an effective inhibitor of angiotensin II action. The possibility that
      the beneficial effects of taurine in the treatment of heart failure might be
      related to its suppression of angiotensin II-mediated cellular responses is
      discussed.

PMID- 9635025
TI  - Effects of taurine on signal transduction steps induced during hypertrophy of rat
      heart myocytes.
AB  - Angiotensin II plays an important role in the development of cardiac hypertrophy.
      One factor thought to contribute to the trophic activity of angiotensin II in
      fibroblasts is the elevation in [Ca2+]i. Although this theory has received
      considerable support in cardiac fibroblasts, it is much more controversial in
      cardiac myocytes. Therefore, the aim of this report was to examine the effect of
      several Ca2+ modulators on protein synthesis in neonatal cardiac myocytes. We
      found that angiotensin II increased both [Ca2+]i and the rate of protein
      synthesis in isolated myocytes. Both effects were blocked by nifedipine, but only
      the angiotensin II-mediated increase in [Ca2+]i was inhibited by taurine in a
      dose-dependent manner. These data support the notion that Ca2+ plays only a
      permissive role in angiotensin II-mediated stimulation of protein synthesis. By
      contrast, the ability of taurine to attenuate the positive chronotropic effect,
      the prolongation of the action potential and the proarrhythmic activity of
      angiotensin II appear to be linked directly to changes in [Ca2+]i. We conclude
      that taurine reverses these actions of angiotensin II by altering Ca2+ flux
      across the cell membrane.

PMID- 9635026
TI  - Effect of taurine depletion on angiotensin II-mediated modulation of myocardial
      function.
AB  - Taurine depletion was induced by either incubation of isolated myocytes with 5 mM
      beta-alanine or feeding rats with water containing 3% beta-alanine. Hearts of
      taurine depleted rats exhibited an impairment in myocardial relaxation,
      associated with a decrease in Na(+)-Ca2+ exchanger activity. Exposure of the
      heart to angiotensin II, an activator of the Na(+)-Ca2+ exchanger, eliminated the
      relaxation defect. In agreement with the contractile results, taurine depletion
      prolonged the calcium transient, an effect which was partially eliminated by
      exposure to angiotensin II. Although peak systolic [Ca2+]i was modestly depressed
      in the taurine depleted myocyte, peak ventricular pressure was normal. This may
      be related to an elevation in pHi induced by taurine depletion. Angiotensin II
      had little effect on contractility of the taurine depleted heart, presumably
      because of two opposing effects, a reduction in pHi and an increase in [Ca2+]i.
      Thus, taurine depletion alters contractile function and ion transport and both of
      these effects are modulated by exposure of the heart to angiotensin II.

PMID- 9635027
TI  - Taurine inhibition of iron-stimulated catecholamine oxidation.

PMID- 9635029
TI  - Uptake of taurine and taurine chloramine in murine macrophages and their
      distribution in mice with experimental inflammation.

PMID- 9635028
TI  - Effects of taurine supplementation on lipid peroxidation, blood glucose and blood
      lipid metabolism in streptozotocin-induced diabetic rats.
AB  - The purpose of this study was to determine the effect of taurine on several
      complications of diabetes, including oxidative stress, glucose intolerance and
      blood lipid profile. Sprague Dawley male rats were fed an experimental diet for 7
      weeks, at which time they were maintained on drinking water with or without 1%
      taurine. The experimental period was 7 weeks and the rats were administered
      streptozotocin (STZ) to induce diabetes. Thiobarbituric acid reactive substances
      (TBARS) content was increased following the STZ injection, but was lowered by
      prior treatment with taurine. The primary diabetic symptoms, such as polydipsia
      and polyuria, were ameliorated in rats supplemented with taurine before the STZ
      injection. Plasma triglyceride (TG) levels of the diabetic group were decreased
      by taurine supplementation, although plasma total cholesterol (T-chol) and HDL
      cholesterol (HDL-chol) were not different among the groups. LDL cholesterol (LDL
      chol) levels of the control group were significantly decreased by taurine
      supplementation, however, the time of taurine administration affected the
      response of the diabetic group; only diabetic rats treated with taurine after the
      administration of STZ showed a decrease in LDL cholesterol. Therefore, taurine
      inhibits lipid peroxidation and decreases blood TG and LDL-chol levels, however,
      the time and dose of taurine supplementation are variables that need to be
      considered in the treatment of diabetes.

PMID- 9635030
TI  - Taurine chloramine inhibits the production of superoxide anion, IL-6 and IL-8 in
      activated human polymorphonuclear leukocytes.

PMID- 9635031
TI  - Myeloperoxidase (MPO) may mediate neutrophil adherence to the endothelium through
      upregulation of CD11B expression--an effect downregulated by taurine.
AB  - Extracellular myeloperoxidase (MPO) is a macrophage modulator which stimulates
      release of the pro-inflammatory cytokine TNF alpha in addition to reactive oxygen
      species (ROS) generated by these cells. MPO-induced macrophage secretion of pro
      inflammatory mediators indirectly upregulates neutrophil pro-inflammatory
      capacity through contributing to neutrophil priming for respiratory burst
      activity. However, to date the question concerning a direct influence on the
      neutrophil by MPO or the MPO-derived product hypochlorous acid (HOCl) remains to
      be elucidated. Taurine, the most abundant free amino acid in human neutrophils
      acts as an antioxidant through the formation of taurine-chloramine by
      sequestering HOCl. Zinc also has antioxidant properties and taurine-zinc
      complexes have been shown to have greater efficacy than either agent alone in
      protection against ROS-mediated tissue damage. The aims of this study were: (a)
      to determine if extracellular MPO modulates the inflammatory response through
      autocrine feedback on the neutrophil and to investigate if taurine either
      directly or indirectly through taurine-chloramine formation may further influence
      this pathway and (b) to evaluate the efficacy of a taurine-zinc combination in
      modulating MPO-induced CD11b receptor expression.

PMID- 9635032
TI  - No beneficial effects of taurine application on oxygen free radical production
      after hemorrhagic shock in rats.
AB  - Oxygen free radical generation contributes to the reinfusion damage after
      hemorrhagic shock. Taurine has been proposed to have radical scavenging
      properties under certain experimental conditions. Therefore the present study was
      undertaken to investigate if taurine would be able to attenuate adverse effects
      of shock/resuscitation in male rats (fasted over night). Under pentobarbital
      anesthesia, hemorrhagic shock (HS) was induced for 1 h by bleeding of the animal
      [mean arterial blood pressure (MAP) = 40 mm Hg] followed by shed blood reinfusion
      and another 1 h period of resuscitation. Rats were divided into two groups:
      Treated rats (n = 6) were injected with taurine (40 mg/kg body mass) prior to
      withdrawal of shed blood; untreated rats (n = 9) received respective volumes of a
      normal saline solution. In untreated animals, free radical induced lipid
      peroxidation was documented by an increase of malondialdehyde (MDA) in the
      systemic circulation (nmol/ml; HPLC measurement) from 1.06 +/- 0.08 during
      normotension (NT) to 1.35+/- 0.18** 1 h after resuscitation (RS). Accordingly,
      plasma levels of alanine aminotransferase (ALT) (11 +/- 2; 35 +/- 12; 94 +/- 44
      U/l, NT; HS; RS) and ammonia (120 +/- 39; 532 +/- 161; 224 +/- 101 micrograms/dl)
      changed significantly during the experimental protocol. Hepatic ATPase-content as
      an indicator of energetic status of the liver fell from 4.8 +/- 0.83 to 0.56 +/-
      0.27 after HS and recovered to only 2.7 +/- 1.6 mumol/g after RS. Leukocyte
      infiltration of the liver was followed by tissue levels of myeloperoxidase (MPO)
      which did not change during HS, but rose during RS (37.9 +/- 18.5; 38.6 +/- 16.4;
      77.5 +/- 24; arbitrary units), documenting an inflammatory reaction after HS.
      Taurine treated rats showed levels of MDA not different from untreated rats after
      RS; also no differences were observed concerning enzyme concentrations and
      ammonia levels. The liver tissue levels of ATP and MPO revealed no differences
      between the two groups during the various periods of the experiment. Liver tissue
      perfusion, as measured by Laser Doppler flowmetry, also did not show significant
      differences between both groups. MAP was significantly higher in the taurine
      treated rats during the first 40 min of resuscitation. It is concluded that even
      a relatively high dose of taurine failed to attenuate the impact of oxygen free
      radicals and did not improve the recovery of the rats during the early
      resuscitation period.

PMID- 9635033
TI  - Influence of taurine supplementation on ischemic preservation of the isolated rat
      kidney.

PMID- 9635034
TI  - Taurine: an osmolyte in mammalian tissues.

PMID- 9635035
TI  - Phospholemman: a cardiac taurine channel involved in regulation of cell volume.

PMID- 9635037
TI  - Adaptations of cerebral volume-regulatory taurine transport to chronic
      disturbances of plasma osmolality.

PMID- 9635036
TI  - Taurine efflux and intracellular pH during astrocyte volume regulation.
AB  - Cytotoxic cerebral edema is characterized by enlarged astroglial cells. In tissue
      culture, osmotically swollen astrocytes return toward normal volume over a period
      of 15-30 min in a process termed regulatory volume decrease (RVD). RVD is due, in
      part, to net efflux of taurine and other amino acids. Our objective in these
      studies was to examine changes in astrocyte intracellular pH (pHi) which may be
      related to taurine loss during RVD. We hypothesized net efflux of anionic taurine
      abandons a proton inside the cell, thus lowering pHi. Primary cultures of
      cerebral astrocytes were prepared from neonatal rats pups and grown on glass
      coverslips. Confluent cells were loaded at 37 degrees C with the fluorescent pH
      indicator BCECF. Fluorescence intensity ratios for excitation wavelengths of 440
      nm and 494 nm (530 nm emission) were computed every 2 sec. Intensity ratios were
      calibrated to pHi at the end of each experiment using 140 mM KCl plus 8.6 microM
      nigericin at pH 7.4. pHi was measured in isoosmotic Hepes-buffered saline (290
      mOsm) and then in hypoosmotic Hepes-buffered saline (200 mOsm) in the presence of
      0.5 mM amiloride. Some solutions also contained 150 microM niflumic acid (NA).
      Cellular taurine content was determined in parallel studies using HPLC. Changes
      in pHi were compared between groups using Student's t-test with Bonferroni
      correction. Significance was assumed if p < 0.05. In isoosmotic saline, mean +/-
      SEM pHi was 7.58 +/- 0.04 and decreased to 7.35 +/- 0.09 after adding amiloride.
      Hypoosmotic exposure caused a further drop in pHi of 0.29 +/- 0.03 within 15 min.
      Recovery of pHi in isoosmotic saline was amiloride-sensitive. Subsequent
      hypoosmotic exposure after recovery in isoosmotic saline produced a change in pHi
      which was 81 +/- 9% of the change measured during the initial hypoosmotic
      exposure. Taurine content decreased from 147 +/- 6 nmol/(mg protein) to 116 +/- 7
      nmol(mg protein) during the 15 min hypoosmotic exposure in 0.5 mM amiloride. NA
      significantly reduced the hypoosmotically induced change in pHi to 0.17 +/- 0.02
      while completely blocking taurine loss. Assuming an intracellular buffering power
      of 13 mM, the NA-sensitive intracellular acidification of cells during
      hypoosmotic exposure in the presence of 0.5 mM amiloride corresponds to 1.6
      mequiv/l additional intracellular H+. This increase in intracellular H+ content
      is equivalent to approximately 32% of the NA-sensitive loss of taurine. The
      association of changes in pHi with taurine efflux is supported by these data;
      however, efflux of other weak acids may contribute to intracellular acidification
      during astrocyte RVD and a significant portion of taurine must leave the cell
      with a proton.

PMID- 9635038
TI  - Effects of steroid hormones and cyclosporine A on taurine-transporter activity in
      the RAW264.7 cell line.
AB  - The activity of the taurine transporter is affected by various extracellular
      stimuli, such as ions, hormones and stress. To assess the effects of steroid
      hormones and cyclosporine A (CsA) on taurine-transporter activity, the murine
      monocytic cell line, RAW264.7, was stimulated with dexamethasone (DM),
      triamcinolone (TA), cortisone (CS), hydrocortisone (HCS), prednisone (PSN),
      prednisolone (PSL) and methylprednisolone (MPSL) in the presence of 12-O
      tetradecanoylphorbol 13-acetate (TPA). Treatment of the cell with TPA led to a
      significant reduction in taurine-transporter activity. However, in the case of
      the stimulation of the cells with steroid hormones in the presence of TPA, all of
      the hormones reversed the TPA-induced reduction in the taurine-transporter
      activity. Treatment of the cells with CsA led to a significant reduction in
      taurine-transporter activity, but ionomycin (IM) alone did not affect taurine
      transporter activity. However, IM reversed the TPA- and CsA-induced reduction in
      taurine-transporter activity. These results showed that both IM and the
      glucocorticoid hormones reversed TPA-induced reductions in taurine-transporter
      activity but only IM reversed the CsA-induced reduction of transporter activity
      in the RAW264.7 cell line.

PMID- 9635039
TI  - The anion-exchanger AE1 is a diffusion pathway for taurine transport in rat
      erythrocytes.

PMID- 9635040
TI  - Molecular cloning and functional expression of an LLC-PK1 cell taurine
      transporter that is adaptively regulated by taurine.
AB  - Studies have shown that the renal tubular epithelium adapts to alterations in the
      sulfur amino acid composition of the diet. The renal adaptive response has been
      described in man, mouse, rat, dog, and pig. The observed phenomenon involves
      increased or decreased initial rate activity of the NaCl-dependent taurine
      transporter at the brush border membrane surface of the proximal tubule following
      dietary manipulation of taurine. A cDNA encoding a taurine transporter has been
      isolated from LLC-PK1 cells, designated pTAUT, and its functional properties have
      been examined in Xenopus laevis oocytes. The nucleotide sequence of the clone
      predicts a 621-amino acid protein with about 90% homology to other cloned taurine
      transporter cDNAs. When expressed in oocytes the transporter displays a Km of 25
      microM and is dependent on the presence of external sodium and chloride,
      characteristics similar to taurine uptake by LLC-PK1 cells. The abundance of
      pTAUT mRNA and protein were up-regulated in cells cultured in taurine-free medium
      as compared with cells cultured in medium containing 500 microM taurine.
      Activation of PKC by PMA had no effect on adaptive regulation of pTAUT mRNA and
      protein, indicating that down-regulation of LLC-PK1 cell taurine transport
      activity by PMA occurs at the post-translational level.

PMID- 9635041
TI  - Regulation of the taurine content in Ehrlich ascites tumour cells.

PMID- 9635042
TI  - Functional consequences of calcium uptake modulation by taurine in vivo and in
      vitro.

PMID- 9635043
TI  - Amplified effect of taurine on PCB-induced hypercholesterolemia in rats.

PMID- 9635044
TI  - Taurine can ameliorate inflammatory bowel disease in rats.
AB  - We previously reported that the protective effect of taurine against indomethacin
      induced gastric mucosal injury was due to its antioxidant effects which inhibited
      lipid peroxidation and neutrophil activation. In this study, we examined the
      effect of taurine on reducing the inflammatory parameters of trinitrobenzene
      sulfonic acid (TNBS)-induced inflammatory bowel disease (IBD) in rats. To induce
      IBD, rats were given ethanolic TNBS intracolonically. The rats then received 500
      mg/kg/day of taurine per orally. The rats were sacrificed one week after IBD
      induction. Ulceration and inflammation of the distal colon with formation of
      granuloma in the vehicle-treated IBD rats after two days of administration of
      TNBS were observed. Treatment with 0.5 g/kg of taurine by the oral route
      ameliorated colonic damage and decreased the incidence of diarrhea and adhesions.
      Colon weight (an index of tissue edema) was markedly increased in the IBD rats
      after administration of TNBS, but was significantly lower after taurine
      treatment. Myeloperoxidase (MPO) activity in the vehicle-treated IBD rats was
      substantially increased compared with that of the control. The taurine-treated
      animals showed reduced MPO activity (35% lower) when compared with that of the
      vehicle-treated animals. Taurine treatment decreased basal and formyl-methionyl
      leucyl phenylalanine (FMLP) stimulated reactive oxygen generation in colonic
      tissue of the IBD rat compared with vehicle treatment after one week. These
      results suggest that administration of taurine reduced the inflammatory
      parameters in this rat model of IBD by increasing the defenses against oxidative
      insult.

PMID- 9635045
TI  - The effects of taurine and biogenetically related sulfur-containing compounds on
      the metabolism of and hypothermia by ethanol in the rat.

PMID- 9635046
TI  - Modification by taurine of the metabolism and hypothermic effect of ethanol in
      the rat.

PMID- 9635047
TI  - Dietary taurine supplementation reduces plasma and liver cholesterol and
      triglyceride levels in rats fed a high-cholesterol or a cholesterol-free diet.
AB  - The effects of dietary taurine supplementation on plasma and hepatic lipid levels
      and phospholipid profiles were evaluated in rats fed a high-cholesterol or a
      cholesterol-free diet. Four groups of male rats were fed one of the following
      diets for 5 weeks: cholesterol-free diet (CFD); high cholesterol diet (HCD); high
      cholesterol, high taurine diet (HCHTD); or high taurine diet (HTD). Rats fed a
      HCHTD had significantly lower plasma levels of total cholesterol (32% reduction),
      LDL-cholesterol (37% reduction) and triglyceride (43% reduction) than rats fed a
      HCD alone. Plasma concentrations of total cholesterol, LDL-cholesterol and
      triglyceride were also significantly reduced in rats fed a HTD compared to rats
      fed a CFD. Taurine supplementation to the HCD significantly reduced hepatic
      cholesterol (50% decrease) and triglyceride (30% decrease) levels in rats.
      Taurine supplementation to the CFD also significantly reduced the hepatic
      triglyceride concentration (43% decrease) and elevated hepatic free fatty acid
      levels (77% increase) compared to rats fed only a CFD. These results suggest that
      dietary taurine supplementation is both hypocholesterolemic and
      hypotriglyceridemic in rats whose body cholesterol status is high or normal.

PMID- 9635048
TI  - Interrelationship between taurine and GABA.

PMID- 9635049
TI  - Regulation of taurine biosynthesis and its physiological significance in the
      brain.
AB  - Cysteine sulfinic acid decarboxylase (CSAD), the rate-limiting enzyme in taurine
      biosynthesis, was found to be activated under conditions that favor protein
      phosphorylation and inactivated under conditions favoring protein
      dephosphorylation. Direct incorporation of 32P into purified CSAD has been
      demonstrated with [gamma 32P]ATP and PKC, but not PKA. In addition, the 32P
      labeling of CSAD was inhibited by PKC inhibitors suggesting that PKC is
      responsible for phosphorylation of CSAD in the brain. Okadaic acid had no effect
      on CSAD activity at 10 microM suggesting that protein phosphatase-2C (PrP-2C)
      might be involved in the dephosphorylation of CSAD. Furthermore, it was found
      that either glutamate- or high K(+)-induced depolarization increased CSAD
      activity as well as 32P-incorporation into CSAD in neuronal cultures, supporting
      the notion that the CSAD activity is endogenously regulated by protein
      phosphorylation in the brain. A model to link neuronal excitation,
      phosphorylation of CSAD and increase in taurine biosynthesis is proposed.

PMID- 9635050
TI  - Cell-damaging conditions release more taurine than excitatory amino acids from
      the immature hippocampus.

PMID- 9635051
TI  - Effects of NO-generating compounds on the uptake and release of taurine in the
      mouse brain.

PMID- 9635052
TI  - The in vivo release of taurine in the striatonigral pathway.

PMID- 9635053
TI  - Taurine-induced potentiation is partially reversed by low-frequency synaptic
      stimulation.

PMID- 9635054
TI  - Treatment of rat brain membranes with taurine increases radioligand binding.

PMID- 9635055
TI  - Taurine modulates glutamate- and growth factors-mediated signaling mechanisms.

PMID- 9635056
TI  - Effect of taurine on human fetal neuron cells: proliferation and differentiation.
AB  - The purpose of this study was to investigate the effect of taurine on human fetal
      brain neuron cell proliferation and differentiation using a glial-free, pure
      cerebral neuronal culture grown in a serum-free environment. We found that
      taurine was necessary for neuronal survival and neurite extension. Taurine, on
      the other hand, has a trophic effect on the human fetal brain cell, promoting
      both proliferation and differentiation. Results showed that DNA synthesis of the
      neurons was increased in a dose-dependent manner when neurons were cultured in
      the medium containing taurine (100-6400 microM). The protein content of neuronal
      cells was also significantly increased in the neurons treated with taurine as
      compared to the control. At day 15, the expression of neuron-specific enolase
      (NSE) was only detected in the neurons cultured in the medium containing taurine.
      These results establish taurine as a putative human fetal brain neurontrophic
      factor in the process of human brain development.

PMID- 9635057
TI  - The role of taurine in osmotic, mechanical, and chemical protection of the
      retinal rod outer segments.
AB  - The ability of the photoreceptor cell to resist osmotic stress was examined by
      incubating isolated frog retina in medium of varying osmolality. An electron
      microscopic analysis of the rod outer segment following a severe hypoosmotic
      insult revealed connections between adjacent disks and between disk rims and the
      plasma membrane, which presumably provide mechanical stability to the rod outer
      segment. One surprising result was the extent of the damage incurred by the
      electrical signaling pathway of the photoreceptor cells subjected to a 50 mOsm
      insult; only the distal P111 component of the ERG remained unaffected. Thus, the
      rod outer segment is particularly resistant to osmotic-induced injury, presumably
      because of the effective osmoregulatory actions of taurine. Incubation of retina
      with tauret, retinylidentaurine, uncovered rose-like hexagonal structures on the
      surface of the rod outer segment. These structures purportedly consist of
      connections between disk rims and the plasma membrane of the rod outer segments.
      Based on the influence of tauret, it is likely that the calcium dependence of
      these channels is selective for retinoids. These data are discussed relative to
      taurine's role in the process of rhodopsin regeneration and in the protection of
      the rod outer segments against osmotic, mechanical and light induced damage.

PMID- 9635058
TI  - Effects of taurine and light on retinal GABA content and the efflux of 14C-GABA
      and 14C-aspartate from frog retina.
AB  - GABA content of isolated, dark adapted frog retina was found to be 3.15 +/- 0.28
      mM. After 30 minutes of exposure to intense light (200 lx), retinal GABA levels
      increased about 70%. Interestingly, incubation of dark adapted retina for 30
      minutes with medium containing 0.4 mM taurine also led to a 70% increase in GABA
      levels. Since the light-induced elevation in GABA content was reduced over 50% by
      a simultaneous injection of 0.02 mM strychinine, it is likely that the light
      induced GABA change is partly mediated by the release of taurine from the retina
      seen after light exposure. However, incubation of isolated retina with medium
      containing increasing concentrations of taurine (1, 2 and 20 mM), caused a
      progressive rise in 14C-GABA efflux from retina that was preloaded with 2.2
      microM GABA and exposed to dim light (0.05 lx). It was also shown that taurine (1
      and 5 mM) dramatically reduced 14C-aspartate efflux from retina preloaded with
      radioactive aspartate and exposed to dim light conditions. By comparison, intense
      light stimulation (40 lx) reduced basal 14C-aspartate efflux while dark exposure
      increased 14C-aspartate loss from the isolated retina. We found that taurine
      depressed the b-wave signal of frog retina, with the maximum effect occurring at
      a concentration of 1 mM. Addition of strychnine (0.4 mM) reversed the taurine
      effect on the b-wave, indicating that taurine receptors must be present in the
      inner retina. By contrast, taurine (0.1-20 mM) had no effect on the P111
      component of the ERG initiated by either aspartate or cobalt. However, taurine
      exerted a modest depressant activity on P111 initiated by glutamate. The
      significance of these data relative to the putative neurotransmitter function of
      taurine in the inner retina is discussed.

PMID- 9635059
TI  - Taurine-stimulated outgrowth from the retina is impaired by protein kinase C
      activators and phosphatase inhibitors.
AB  - Taurine increases neurite elongation of post-crush goldfish retinal explants, as
      well as the number of outgrowing isolated cells from goldfish and rat retina in
      culture. The trophic effect of taurine is related to an elevation in calcium flux
      rather than increased cell proliferation. Since taurine regulates phosphorylation
      in rat retina, we investigated if this process could be involved in the mechanism
      of taurine action on outgrowth. Control and taurine-supplemented post-crush
      goldfish retinal explants were cultured in the presence of protein kinase C
      activators or phosphatase inhibitors, and the length of neurites was measured
      after five days in culture. In some cases, there was an inhibition of the
      stimulatory effect of taurine without a modification in basal outgrowth. In
      others, outgrowth of control explants was also reduced. A certain level of
      protein phosphorylation seems to be critical for the trophic effect of taurine in
      the retina.

PMID- 9635060
TI  - Unique pharmacological interactions of taurine and chelerythrine in the retina.
AB  - The effects of taurine and chelerythrine (CHT) on ATP-dependent calcium uptake
      and the phosphorylation of the approximately 20 kDa phosphoprotein in the retina
      were compared. In the absence of the CHT, taurine stimulated ATP-dependent
      calcium uptake and attenuated the phosphorylation of the approximately 20 kDa
      phosphoprotein. On the other hand, CHT produced the opposite results in the
      absence of taurine. When the two agents were used simultaneously, it was found
      that CHT non-competitively inhibited the action of taurine to stimulate calcium
      uptake, while taurine non-competitively inhibited the action of CHT to stimulate
      the phosphorylation of the approximately 20 kDa phosphoprotein. The data present
      an unusual pharmacological mechanism for controlling the signal transduction
      pathway involving the two distinct cellular processes being studied. Given the
      unique data, a control system is proposed in which the function of the
      approximately 20 kDa phosphoprotein is linked to the stimulation of ATP-dependent
      calcium uptake.

PMID- 9635061
TI  - Increased phosphorylation of specific rat cardiac and retinal proteins in taurine
      depleted animals: isolation and identification of the phosphoproteins.
AB  - Partial depletion of the tissue levels of taurine in the alive animal stimulates
      in vitro phosphorylation of both an approximately 20 kDa (94%) and an
      approximately 44 kDa (85%) protein present in subcellular fractions of the rat
      retina and heart. Tissue levels of taurine were reduced by feeding the animals
      1.5% guanidinoethanesulfonic acid (GES) in their drinking water for 6 weeks. The
      increase in the in vitro phosphorylation of both the approximately 20 kDa and
      approximately 44 kDa proteins was reversed when the animals were subsequently
      given 1.5% taurine in their drinking water for an additional 6 weeks. Isolation,
      purification, tryptic digestion, and peptide sequence analysis of the retinal
      approximately 20 kDa phosphoprotein suggest that it is histone H2B. However, the
      results are ambiguous due to an impurity (< 25%) in the retinal preparation.
      Sequence analysis of the approximately 44 kDa phosphoprotein indicates that it is
      pyruvate dehydrogenase.

PMID- 9635062
TI  - Extensive taurine depletion and retinal degeneration in cats treated with beta
      alanine for 40 weeks.

PMID- 9635063
TI  - The role of taurine in infant nutrition.
AB  - The importance of taurine in the diet of pre-term and term infants has not always
      been clearly understood and is a topic of interest to students of infant
      nutrition. Recent evidence indicates that it should be considered one of the
      "conditionally essential" amino acids in infant nutrition. Plasma values for
      taurine will fall if infants are fed a taurine-free formula or do not have
      taurine provided in the TPN solution. Urine taurine values also fall, which is
      indicative of an attempt by the kidney to conserve taurine. The very-low-birth
      weight infant, for a variety of reasons involving the maturation of tubular
      transport function, cannot maximally conserve taurine by enhancing renal
      reabsorption and, hence, is potentially at greater risk for taurine depletion
      than larger pre-term or term infants, and certainly more than older children who
      have taurine in their diet. Taurine has an important role in fat absorption in
      pre-term and possibly term infants and in children with cystic fibrosis. Because
      taurine-conjugated bile acids are better emulsifiers of fat than glycine
      conjugated bile acids, the dietary (or TPN) intake has a direct influence on
      absorption of lipids. Taurine supplementation of formulas or TPN solutions could
      potentially serve to minimize the brain phospholipid fatty acid composition
      differences between formula-fed and human milk-fed infants. Taurine appears to
      have a role in infants, children, and even adults receiving most (> 75%) of their
      calories from TPN solutions in the prevention of granulation of the retina and
      electroencephalographic changes. Taurine has also been reported to improve
      maturation of auditory-evoked responses in pre-term infants, although this point
      is not fully established. Clearly, taurine is an important osmolyte in the brain
      and the renal medulla. At these locations, it is a primary factor in the cell
      volume regulatory process, in which brain or renal cells swell or shrink in
      response to osmolar changes, but return to their previous volume according to the
      uptake or release of taurine. While there is a dearth of clinical studies in man
      concerning this volume regulatory response, studies in cats, rats, and dog kidney
      cells indicate the protective role of taurine in hyperosmolar stress. The infant
      depleted of taurine may not be able to respond to hyper- or hyponatremic stress
      without massive changes in neuronal volume, which has obvious clinical
      significance. The fact that the brain content of taurine is very high at birth
      and falls with maturation may be a protective feature, or compensation for renal
      immaturity Defining an amino acid as "conditionally essential" requires that
      deficiency result in a clinical consequence or consequences which can be reversed
      by supplementation. In pre-term and term infants, taurine insufficiency results
      in impaired fat absorption, bile acid secretion, retinal function, and hepatic
      function, all of which can be reversed by taurine supplementation. Therefore,
      this small beta-amino acid, taurine, is indeed conditionally essential.

PMID- 9635064
TI  - Quantitation of taurine and selenium levels in human milk and estimated intake of
      taurine by breast-fed infants during the early periods of lactation.
AB  - With these results we report the following: Taurine levels in human milk
      decreased slightly during the early lactation period. The concentration of
      taurine (406 +/- 174 nmol/ml) in colostrum was significantly higher than that
      (335 +/- 115 nmol/ml) in mature milk. Selenium content of human milk also
      decreased slightly during the early lactation period. The content of selenium
      (28.6 +/- 19.6 ng/ml) in colostrum was significantly higher than that (1 5.1 +/-
      5.9 ng/ml) in mature milk. A correlation was not found between the taurine and
      selenium content of human milk. The intake of taurine and selenium by breast-fed
      infants progressively increased with days postpartum. These results were due to
      the significant increase in milk intake by infants. It is suggested that the
      taurine and selenium levels in colostrum are more concentrated than those in
      mature milk. However, the absolute intake of taurine and selenium by infants are
      higher in mature milk.

PMID- 9635065
TI  - Plasma concentration of taurine is higher in malnourished than control children:
      differences between kwashiorkor and marasmus.
AB  - Plasma free amino acids were determined in the plasma of severely malnourished
      children under two years of age. A total of thirty-one patients and eleven
      controls were evaluated: seventeen cases of kwashiorkor, eight cases of marasmus,
      and six cases of marasmic-kwashiorkor. Fasting plasma samples were taken in the
      morning on the day of admission. Fasting plasma samples were also taken from nine
      patients at discharge after two months in the hospital where they received a
      balanced diet as treatment. A partial reversal of the signs of malnutrition was
      observed at discharge. In the whole group of patients ad admission, lower
      concentrations of tyrosine, methionine, tryptophan, and leucine and higher
      concentrations of aspartate, glutamate, and taurine were observed compared to
      controls. Taurine continued to be elevated in the malnourished group at the time
      of discharge. Marasmic children, as compared to controls, had high aspartate and
      low tryptophan levels, but taurine levels were not significantly different from
      controls. Kwashiorkor patients had low tyrosine, methionine, tryptophan, and
      lysine, and significantly higher taurine plasma levels. The elevated
      concentration of taurine might be the result of a redistribution of this amino
      acid to provide specific tissues with the required amount for development.

PMID- 9635066
TI  - The effect of dietary sulfur-containing amino acids on calcium excretion.
AB  - The relationships between dietary protein and sulfur amino acid (methionine and
      cystine or taurine) intakes and urinary calcium excretion were examined both in
      animals and in young men. Thirty-two adult Wistar rats were divided into 4
      groups, i.e., basal diet (group I), supplemented with albumin (II), methionine
      and cystine (III), or taurine (IV). During the 5-week feeding period, food
      consumption was recorded and 48 h urine samples were collected 4 times for each
      rat. Urinary calcium, creatinine and sulfate were measured. The results showed
      that the calcium and sulfate excretion in rats in group II and III were
      significantly higher than rats in the basal diet group. In contrast,
      supplementing a basal diet with taurine did not increase sulfate excretion and
      failed to induce hypercalciuria. The same result was also observed in the study
      carried out in Chinese young men. An increase in protein intake from 67 g to 107
      g caused an increase in urinary calcium and sulfate. Supplementation with
      methionine and cystine in an amount to simulate those in the high protein diet
      had a similar effect. Adding taurine to the diet had no effect on urinary calcium
      and sulfate excretion. About 60 percent of the supplemented taurine in the diet
      was detected in the urine.

PMID- 9635067
TI  - Taurine content in Chinese food and daily intake of Chinese men.
AB  - The taurine content in Chinese food, including seafood, fresh water fish, meats
      and some plants, was examined in this study. Seafood was freshly collected from 4
      coastal areas in China. Meat and plant food samples were obtained from food
      markets. The highest concentration of taurine was found in crustaceans and
      molluses (300-800 mg per 100 g edible portion). The amount of taurine in fish was
      variable. Beef, pork and lamb contained taurine in concentrations ranging from 30
      160 mg per 100 g. No taurine was detected in hen eggs and plants. The daily
      taurine intake of representative Chinese men (18-45 years old, 60 kg body weight,
      light physical activity) was also studied in 1990 as a part of the Total Diet
      Study. Representative food samples were collected from 12 provinces in 4 areas of
      China. Samples were then combined and cooked according to food categories (meat,
      seafood, vegetables, etc) The combined meat and seafood samples were analyzed for
      taurine. The daily taurine intake of a standard man in the 4 areas was calculated
      based on the amount of food intake obtained from the dietary survey and the
      taurine concentration in the analyzed food samples. The result showed that the
      daily taurine intake of a standard Chinese man in the 4 different test areas
      ranged from 34 to 80 mg per day.

PMID- 9635068
TI  - Effects of dietary taurine on auditory function in full-term infants.
AB  - Three groups of neonates fed taurine supplemented infant formula, non
      supplemented infant formula or breast milk, respectively, were studied from birth
      to 12 weeks of age. In addition to the measurement of whole blood taurine
      content, auditory function was monitored using auditory brainstem responses
      (ABRs) and transient evoked otoacoustic emissions (TEOAEs). The results showed a
      significant reduction in whole blood taurine concentration in the non
      supplemented formula group. In addition, there was a significant drop in whole
      blood taurine levels in all 3 groups over the first four weeks of life. ABR wave
      latencies were significantly shorter in the non-supplemented group, with wave V
      showing the greatest reductions. Falling taurine levels after full-term birth may
      aid synaptic maturation/efficiency within the auditory system. TEOAE responses
      were significantly larger over the low to mid frequencies in the breast fed group
      suggesting improved middle ear function.

PMID- 9635069
TI  - Relationship of childhood abuse and household dysfunction to many of the leading
      causes of death in adults. The Adverse Childhood Experiences (ACE) Study.
AB  - BACKGROUND: The relationship of health risk behavior and disease in adulthood to
      the breadth of exposure to childhood emotional, physical, or sexual abuse, and
      household dysfunction during childhood has not previously been described.
      METHODS: A questionnaire about adverse childhood experiences was mailed to 13,494
      adults who had completed a standardized medical evaluation at a large HMO; 9,508
      (70.5%) responded. Seven categories of adverse childhood experiences were
      studied: psychological, physical, or sexual abuse; violence against mother; or
      living with household members who were substance abusers, mentally ill or
      suicidal, or ever imprisoned. The number of categories of these adverse childhood
      experiences was then compared to measures of adult risk behavior, health status,
      and disease. Logistic regression was used to adjust for effects of demographic
      factors on the association between the cumulative number of categories of
      childhood exposures (range: 0-7) and risk factors for the leading causes of death
      in adult life. RESULTS: More than half of respondents reported at least one, and
      one-fourth reported > or = 2 categories of childhood exposures. We found a graded
      relationship between the number of categories of childhood exposure and each of
      the adult health risk behaviors and diseases that were studied (P < .001).
      Persons who had experienced four or more categories of childhood exposure,
      compared to those who had experienced none, had 4- to 12-fold increased health
      risks for alcoholism, drug abuse, depression, and suicide attempt; a 2- to 4-fold
      increase in smoking, poor self-rated health, > or = 50 sexual intercourse
      partners, and sexually transmitted disease; and 1.4- to 1.6-fold increase in
      physical inactivity and severe obesity. The number of categories of adverse
      childhood exposures showed a graded relationship to the presence of adult
      diseases including ischemic heart disease, cancer, chronic lung disease, skeletal
      fractures, and liver disease. The seven categories of adverse childhood
      experiences were strongly interrelated and persons with multiple categories of
      childhood exposure were likely to have multiple health risk factors later in
      life. CONCLUSIONS: We found a strong graded relationship between the breadth of
      exposure to abuse or household dysfunction during childhood and multiple risk
      factors for several of the leading causes of death in adults.

PMID- 9635070
TI  - Youth violence in the United States. Major trends, risk factors, and prevention
      approaches.
AB  - Violence among youths is an important public health problem. Between 1985 and
      1991, homicide rates among youths 15-19 years of age increased 154% and remain,
      today, at historically high levels. This paper reviews the major trends in
      homicide victimization and perpetration among youths over the last decade, the
      key risk factors associated with violence, and summarizes the many primary
      prevention efforts under way to reduce violence. Previous research points to a
      number of factors that increase the probability of violence during adolescence
      and young adulthood. Some of these factors include the early onset of aggressive
      behavior in childhood, social problem-solving skill deficits, exposure to
      violence, poor parenting practices and family functioning, negative peer
      influences, access to firearms, and neighborhoods characterized by high rates of
      poverty, transiency, family disruption, and social isolation. Efforts to address
      some of the primary risk factors for violence are under way across the United
      States, but evaluations to confirm program effectiveness are needed.

PMID- 9635071
TI  - Family violence curricula in U.S. medical schools.
AB  - INTRODUCTION: Family violence (adult domestic violence, child abuse/neglect, and
      elder abuse) is endemic. Victims of family violence are seen in every venue of
      health care, yet physicians do not routinely inquire about abuse, even when
      patients present with obvious clinical characteristics. Although a comprehensive
      health care response is key to a coordinated community-wide approach to family
      violence, most practicing physicians have never received education in any aspect
      of family violence, including child abuse. This paper reports the results of a
      survey of family violence instruction in medical schools. METHODS: A written
      survey of medical school deans and student representatives of all 126 U.S.
      medical schools was conducted to (1) determine curriculum content in family
      violence, (2) assess differences between deans' and students' perceptions of
      curricular offerings, and (3) compare the results of the current survey with
      those of an earlier curriculum survey conducted in 1987. RESULTS: The majority of
      deans reported existing curriculum in all three topic areas of family violence.
      Compared to the 1987 survey, more deans reported existing curriculum in family
      violence. However, neither total instructional time nor curriculum during
      clinical training increased. Moreover, student and dean responses were discrepant
      regarding awareness of curriculum in domestic violence and elder abuse.
      CONCLUSION: Despite an increase in the number of schools reporting curriculum in
      family violence, there does not appear to be increased attention to this problem,
      at least as measured by time devoted to teaching. Insights from this descriptive
      survey can promote ongoing efforts toward comprehensive curriculum development in
      family violence.

PMID- 9635072
TI  - Recommended components of health care provider training programs on intimate
      partner violence.
AB  - Programs that are effective in training health care providers to recognize and
      meet the needs of victims of intimate partner violence must be identified and
      replicated. The Centers for Disease Control and Prevention (CDC) has developed
      criteria for use in developing, enhancing, and evaluating such programs. CDC
      developed these criteria as a result of continuing efforts to provide useful
      products for constituents through literature reviews and consultations with
      experts in the field; evaluations of training programs; creation of an inventory
      and annotated bibliography of health care provider training programs in the
      United States and Canada; and development of a framework to assist hospitals and
      health centers in evaluating their training programs. Training should begin while
      providers are in professional school and continue in the health care setting.
      Curricula should be multidisciplinary and should provide information, promote
      clinical skills, and effectively link providers with resources. Evaluation should
      assist programs in determining providers' needs and identifying appropriate
      materials, trainers, and training strategies. CDC is working to establish
      scientific evidence that provider training programs are effective and to share
      successful models with others. Providers have an important role in stopping and
      ultimately preventing intimate partner violence, but they are not alone in this
      effort. They need to know how to access the growing network of assistance
      including women's advocates, the criminal justice system, and other members of
      increasingly dynamic community coalitions.

PMID- 9635073
TI  - Assessing family violence interventions.

PMID- 9635074
TI  - Commentary on the federal role in clinical prevention research.
AB  - Effective clinical prevention practice is the objective of the long journey from
      laboratory and epidemiologic studies to clinical understanding, interventions,
      and prevention practice with individual patients. The ability to ask ever more
      fundamental questions about the molecular basis of disease, as is rapidly being
      developed by NIH's Human Genome Project, promises to make this journey even
      longer and more complicated, but eventually to make screening and intervention
      for preventable disease even more amenable to clinical intervention. As we expect
      in the future, much of what we currently do in clinical prevention practice had
      its genesis in earlier federal support for basic and clinical research. We
      comment on the content and major points of the papers on the federal role in
      prevention research. These papers, in addition to describing the past
      accomplishment, current state, and future opportunities for prevention research,
      raise questions about the ultimate application of the enormous and successful
      national investment in prevention research. A fault line exists among the
      increasing knowledge of prevention practice, the rapid changes in the way
      services are delivered, and demonstration of the effectiveness of prevention
      procedures applied for the good of the whole population. The federal agencies
      most concerned with the application of prevention knowledge are those most
      limited in their research budgets: the Agency for Health Care Policy and Research
      (AHCPR) and the Centers for Disease Control and Prevention (CDC). The National
      Institutes of Health (NIH), with the greatest research dollars for investment,
      also has the broadest mandate for investment in research. Meeting all the demands
      to fund high-quality research is challenging; however, NIH may have review
      procedures that disadvantage clinical researchers and, among these, applied
      prevention researchers. The restructuring of the health care system by managed
      care promises opportunity for more effectiveness research. However, the same
      competition that fosters the development of managed care may limit the extent of
      prevention experimentation and the dissemination of results. Current national
      concerns for the weakening of support for clinical research are in part due to
      the reduced availability of patient care revenue to support clinical research
      brought about by managed care. The academic and practice communities that share
      concern for prevention research should recognize the increasing gap between basic
      and applied prevention knowledge. Those committed to the clinical application of
      this knowledge should encourage increased federal research support to assure that
      what we think we know is indeed so, that what is efficacious is available to all
      in the society that so generously supports research.

PMID- 9635075
TI  - Clinical preventive services research.

PMID- 9635076
TI  - Prevention research at the National Institutes of Health.
AB  - Prevention of disease and disability and preservation of health are compelling
      strategies that are endorsed by the public, health care providers, and
      researchers. Despite this general acceptance of the concept, the "devil is in the
      details." What can and should be recommended with confidence to the public and
      health care providers regarding prevention and how can these recommendations be
      implemented? Prevention programs should be based on durable evidence of efficacy
      and should assure that the benefits of interventions and changes exceed the
      risks. The latter is particularly important for population-based primary
      prevention because many are influenced but fewer may benefit. Prevention research
      must provide the evidence of benefit and risk. The responsibility of the National
      Institutes of Health (NIH) is to develop the scientific basis for prevention and
      to train prevention scientists who are responsible for creating this science
      base. The interpretation and dissemination of information from research studies
      are important and necessary aspects to assure translation of the science into
      personal and public health practices. The components of prevention research are
      investigation of the factors that place individuals and groups at risk of disease
      and disability; trials of the interventions that can modify this risk; and
      testing the approaches that can effectively implement beneficial changes. NIH is
      committed to addressing these endeavors, and its individual Institutes and
      Centers support a broad portfolio of prevention research. This paper will provide
      an overview of NIH support, the functional relationships of prevention research
      within NIH, and background information that can be useful to those interested in
      research.

PMID- 9635077
TI  - Fifty years of applied population-based prevention research at the Centers for
      Disease Control and Prevention.

PMID- 9635078
TI  - Cardiovascular disease prevention research at the National Heart, Lung, and Blood
      Institute.

PMID- 9635079
TI  - Health services research agenda for clinical preventive services.

PMID- 9635080
TI  - Broadening the evidence base for evidence-based guidelines. A research agenda
      based on the work of the U.S. Preventive Services Task Force.
AB  - Evidence-based evaluations of clinical preventive services help define priorities
      for research in prevention as part of primary health care. In this article, we
      draw on our experiences with the U.S. Preventive Services Task Force (USPSTF) to
      outline some major areas where research is needed to define the appropriate use
      of specific screening tests, counseling interventions, immunizations, and
      chemoprophylaxis. Areas of particular importance included research to: (1)
      Identify effective and practical primary care interventions for modifying
      personal health practices of patients, especially around issues such as diet,
      exercise, alcohol and drug use, and risky sexual behavior; (2) Clarify the
      optimal periodicity for certain screening tests and counseling interventions; (3)
      Identify practical ways to allow patients to share decision-making about
      preventive care, especially for services of possible but uncertain benefit; (4)
      Examine the most sensitive and efficient ways to identify high-risk groups who
      may need different services than the average population; and (5) Expand the use
      of decision-analysis and cost-effectiveness analysis to help identify optimal use
      of clinical preventive services. Given the difficulty of large, prospective
      trials, we discuss the use of alternative research designs to fill in critical
      gaps in the evidence for the effectiveness of specific services. Finally, we note
      several issues of increasing importance that may need to be addressed by future
      work of the USPSTF: what are the most reliable and effective ways to (1) measure
      and (2) improve the delivery and quality of preventive care provided in the
      primary care setting.

PMID- 9635081
TI  - Prevention and primary care research for children. The need for evidence to
      precede "evidence-based".
AB  - Medical care in the United States continues to face tremendous financial
      pressures. Public and private health policy claim to encourage primary care and
      preventive services, but also discourage services that have not been demonstrated
      to be effective and/or cost-effective. This article suggests a model to
      illustrate the conceptual relationship between traditional American medical care
      and "evidenced-based" medicine. It further examines how the lack of an adequate
      research base makes a move to purely evidence-based care premature for primary
      care and prevention services. The paper defines a new conceptual statistic, the
      uncertainty index, as the proportion of non-refuted current practice that is also
      not corroborated by research evidence. The greater the uncertainty index, the
      less appropriate is a clinical model restricted to evidence-based care. Specific
      theoretical barriers to outcomes research in prevention are discussed and simple
      criteria to determine the desirable components of care are suggested. The need
      for theoretical and empirical research into primary care and prevention,
      especially for children, is emphasized. Care that is of low risk, not of
      extremely high cost, and that is generally believed useful by the community of
      practitioners is particularly desirable in the absence of data refuting its
      value.

PMID- 9635082
TI  - Prevention research. A call to action.

PMID- 9635083
TI  - Adverse childhood experiences. A public health perspective.

PMID- 9635084
TI  - What explains the negative consequences of adverse childhood experiences on adult
      health? Insights from cognitive and neuroscience research.

PMID- 9635085
TI  - Adverse childhood experiences and trauma.

PMID- 9635086
TI  - In response to the September-October article entitled "Violence and adverse
      pregnancy outcomes: a review of the literature and directions for future
      research".

PMID- 9635087
TI  - DoEpi. Computer-assisted instruction in epidemiology and computing and a
      framework for creating new exercises.
AB  - DoEpi is a series of computer exercises and a framework for making new exercises
      based on the Epi Info programs for epidemiologic computing. The system contains
      three outbreak investigations, a research survey, four exercises in advanced Epi
      Info programming, and four exercises in public health surveillance. The exercises
      are available via the Internet (www.cdc.gov, under "Publications, Products, and
      Software") with provision for CME and CEU credit from the Centers for Disease
      Control and Prevention. They can serve as a useful adjunct to lectures and
      textbooks in teaching epidemiology or epidemiologic computing. A new DoEpi
      exercise with hypertext, low-resolution photographs, questions, answers, and an
      examination can be constructed in hours rather than weeks or months using an
      Exercise Development "wizard" provided as part of the instructor's module. Epi
      Info exercises with data files and customized programs require more work to
      construct but can be added by those with the necessary skills. DoEpi exercises
      can be used in a variety of ways for different curricula and students of
      different background levels, including those with English as a second language.
      Translation of DoEpi exercises into other languages is facilitated by the
      instructor's module, and construction of new exercises with locally suitable
      materials is encouraged. DoEpi is based on DOS programs to allow the widest use.
      The format lends itself to conversion to hypertext programs in the Microsoft
      Windows and Internet formats at a future date.

PMID- 9635089
TI  - The U.S. Preventive Services Task Force Guide to Clinical Preventive Services,
      Second Edition. AMA Council on Scientific Affairs.
AB  - A resolution, introduced by the American College of Preventive Medicine at the
      1996 American Medical Association (AMA) Annual Meeting, asked the AMA to
      recommend to physicians the use of the United States Preventive Services Task
      Force's Guide to Clinical Preventive Services, Second Edition. In response to
      that resolution, the AMA's Council on Scientific Affairs has reviewed and
      evaluated this publication. The recommendations of the Council on Scientific
      Affairs on the use of the Guide to Clinical Preventive Services, Second Edition,
      by clinicians and medical educators are included in this report. These
      recommendations were adopted as AMA Policy at the AMA Annual Meeting in June
      1997.

PMID- 9635090
TI  - Increased frequencies of cytochrome P4501A1 polymorphisms in infertile men.
AB  - Genetic factors that could mediate the pathogenesis of male reproductive
      disorders are largely unclear. Polymorphisms of cytochrome P4501A1 (CYP1A1), a
      key enzyme in the extrahepatic metabolism of lipophilic xenobiotics, have been
      shown to influence susceptibility to xenobiotics. Here, CYP1A1 polymorphisms were
      investigated in 134 infertile Caucasian men. The frequencies of the Mspl
      polymorphism in the 3'-flanking region of the CYP1A1 gene and a mutation in exon
      7 causing an isoleucine-valine exchange (IVE) in the heme-binding region of the
      enzyme were increased among infertile men when compared with those of unselected,
      healthy male controls (odds ratio (OR)) 1.4, Cl95 0.68-2.89 for Mspl
      polymorphism; OR 2.4, Cl95 0.83-6.95 for IVE). Patients with normozoospermia
      revealed the highest frequencies for both polymorphisms (n = 8; OR 4.5, Cl95 0.97
      20.91 for Mspl polymorphism; OR 13.7, Cl95 2.53-74.13 for IVE). ORs for the IVE
      exceeded the values calculated for the Mspl polymorphism. These preliminary
      results suggest that genetic variation in the metabolism of xenobiotics may
      codetermine individual susceptibility to infertility.

PMID- 9635091
TI  - Effect of chronic administration of Tamoxifen on fertility in male bonnet monkeys
      (Macaca radiata).
AB  - Administration of Tamoxifen via the Alzet pump at a rate of 50 micrograms hr-1
      for 90 days in the adult male bonnet monkeys Macaca radiata had no effect on the
      serum testosterone concentration determined at 10 AM and 10 PM as well as total
      sperm count determined at 15-day intervals over a period of 260 days. However, a
      significant reduction in sperm motility was observed beyond 90 days up until the
      225th day. Breeding studies conducted from day 90 to 260 revealed that these
      males were infertile.

PMID- 9635092
TI  - A comparative study of the EpiScreen kit and a conventional method for the
      determination of seminal alpha-glucosidase activity.
AB  - Low alpha-glucosidase activity in seminal plasma is a marker of epididymal
      obstruction. The criterion standard for determining activity is the epididymal
      specific method, whereby the neutral iso-enzyme, specifically produced by the
      epididymis, is measured. A kit that determines total alpha-glucosidase activity
      (neutral iso-enzyme and the acid iso-enzyme originating from the prostate) has
      become available. The objective of the laboratory-based study was to compare
      alpha-glucosidase activity values measured by both the EpiScreen and the
      epididymal specific method, to determine if the kit may provide reliable results
      to substitute the neutral iso-enzyme specific method in the routine clinical
      setting. The neutral iso-enzyme activity according to both methods was measured
      in seminal plasma of 23 post-vasectomy and 24 normozoospermic patients.
      Significant differences (P < 0.05) were found between the activities measured
      according to both methods, but these differences pertained mostly to high values
      (> 40 mU ejaculate-1), which was not clinically significant. In conclusion, the
      epididymal specific method is best suited for research purposes, but the
      EpiScreen kit is convenient for routine use in infertility clinics.

PMID- 9635093
TI  - Measurement of calcium influx in surface-fixed single sperm cells: efficiency of
      different immobilization methods.
AB  - Calcium fluxes across the plasma membrane of spermatozoa are part of the signal
      transduction pathway during sperm capacitation. To identify the topography, the
      time sequence and frequency of calcium fluxes in motile human spermatozoa,
      individual spermatozoa have to be locally immobilized in a measurement chamber to
      allow the quantification of ionized calcium by use of a microspectro-photometric
      method (FURA-2AM). In this study, we compared different immobilization methods
      using agarose-, gelatin-, laminin- and poly-L-lysine-coated glass slides. Optimal
      results were obtained with poly-L-lysine coating, which permitted the adhesion of
      motile spermatozoa that could be analysed microspectro-photometrically. The loss
      of adherent spermatozoa during the washing procedures was below 10%. However, a
      major disadvantage of poly-L-lysine coating is that this polymer itself induces a
      low calcium flux in spermatozoa. Comparing all tested variations, laminin offered
      the best adhesion result without any detectable effects on calcium fluxes. Our
      method allowed the rapid change of incubation fluid and calcium concentrations
      around individual motile spermatozoa and the reproducible quantification of
      calcium fluxes in single motile spermatozoa.

PMID- 9635094
TI  - Heterogeneity in the presence of CD4-like molecules on human spermatozoa.
AB  - The object of the present study was to study if there are differences in the
      presence of CD4-like molecules on human ejaculated spermatozoa in fertile donors
      and infertile patients (with globozoospermia). Indirect and absorption enzyme
      linked immunosorbent assay and indirect immunofluorescence were applied. The
      enzyme-linked immunosorbent assay data showed that monoclonal anti-human CD4
      antibody recognizes an epitope common to the human spermatozoa with normal
      morphology and round-headed spermatozoa. Localization of the antigenic
      determinants, identified by anti-human CD4-monoclonal antibody, in the acrosomal
      region, including equatorial segment, postnuclear cap and tail was determined in
      normozoospermic samples. A positive reaction was found on the sperm head both in
      the acrosomal and postacrosomal region of some round-headed spermatozoa in the
      samples with globozoospermia. The tails of the normozoospermic spermatozoa and of
      some round-headed spermatozoa were weakly immunopositive. The results of the
      experiments carried out are evidence of heterogeneity in the presence of CD4-like
      antigen determinants on human spermatozoa. These data increased the information
      about the CD4-antigen characteristic of the spermatozoa from fertile donors and
      infertile patients.

PMID- 9635095
TI  - Wave parameters of the sperm flagellum as predictors of human spermatozoa
      motility.
AB  - We characterized the undulatory movement of the sperm's flagellum as a sigmoid
      wave by measuring the absolute and linear speed of the sperm, period, amplitude
      and length of the flagellum's wave, and the segment comprised between the head
      and the origin of the movement in the flagellum. These parameters were correlated
      with traditional ones used to determine the pattern of movement of the sperm. Our
      results show that wave parameters are useful predictors of sperm motility. They
      correlate among themselves, and thus, a few wave parameters may characterize the
      sperm motility. The advantage of wave parameters is that they can be easily
      obtained and can be eventually associated to the sperms' internal morphology.

PMID- 9635096
TI  - Induction of acrosome reaction by low temperature is comparable to physiological
      induction by human follicular fluid.
AB  - The acrosome reaction was induced by means of low temperature or human follicular
      fluid (FF) in spermatozoa from 18 patients. Live acrosome-reacted spermatozoa
      were determined with the triple-stain technique. Both inducers of acrosome
      reaction had a highly significant correlation with the percentage of acrosome
      reacted spermatozoa after induction of the acrosome reaction: (r = 0.9190; P <
      0.0001) and the inducibility of AR (r = 0.8472; P < 0.0001). This might indicate
      that both the non-physiological (low temperature) and the physiological (FF)
      inducers use the same signal transduction pathway, and demonstrates the
      usefulness of low temperature induction for diagnostic purposes.

PMID- 9635097
TI  - Effect of bradykinin on kinematic parameters of human spermatozoa.

PMID- 9635098
TI  - Carbohydrate deficient transferrin measurement.

PMID- 9635099
TI  - Rational use of clinical chemistry investigations: from diagnoses to processes.

PMID- 9635100
TI  - Standardization of steroid hormone assays.

PMID- 9635101
TI  - CA 19-9 as a marker for gastrointestinal cancers: a review.

PMID- 9635102
TI  - Traceability and uncertainty in analytical measurements.

PMID- 9635103
TI  - Cardiac troponins in patients with renal dysfunction.
AB  - Cardiac troponin T (cTnT) and cardiac troponin I (cTnI) were measured in 198
      patients with renal dysfunction [132 men: median (range) age 66.1 (8.2-90.3)
      years]. cTnT was measured by two methods: ELISA and Enzymun (Boehringer Mannheim
      UK, Lewes, UK), both with a detection limit of 0.05 microgram/L in 179 and 78
      patients, respectively. cTnI was measured in 80 patients by the OPUS plus and
      OPUS Magnum systems (Dade-Behring, Milton Keynes, UK) with a detection limit of
      0.5 microgram/L. Patients were classified as having chronic renal impairment
      (CRI), chronic renal failure (CRF), acute renal failure including those with
      multiple organ failure on renal replacement therapy (ARF), and patients with
      chronic renal failure treated with haemodialysis (HD). Cardiac troponins were
      detectable in the serum of patients with renal dysfunction. cTnT was detectable
      in 113/179 (63.1%) and 33/78 (42.3%) by the ELISA and Enzymun methods
      respectively. cTnI was detectable in 17/80 (21.3%). cTnT (ELISA and Enzymun
      methods) and cTnI were detectable with increased frequency in the CRF, HD and ARF
      patient groups compared with the CRI group. Cardiac troponin concentrations did
      not correlate with serum creatine kinase (CK) activity, CK-MB, or urea or
      creatinine levels. Serial cardiac troponin measurements may be required to
      confirm or exclude a diagnosis of acute coronary syndromes in patients with renal
      dysfunction.

PMID- 9635104
TI  - Clinical and biochemical determinants of plasma lipid peroxide levels in type 2
      diabetes.
AB  - The enhanced risk and increased severity of atheroma in diabetes is well
      recognized but, as yet, incompletely explained. A cross-sectional study of
      vascular disease risk factors in a group of type 2 diabetic patients from South
      West Scotland has revealed an association between glycaemic control, assessed by
      HbAl level and plasma lipid peroxides measured by a specific high-performance
      liquid chromatography method. Duration of diabetes appeared to be a subsidiary
      contributor to lipid peroxidation. We suggest this evidence supports the
      importance of glycaemic control in modulating glyco-oxidative mechanisms probably
      crucial to production of diabetic complications. Atherosclerosis prevention in
      diabetes may hinge on exemplary simultaneous control of both hyperglycaemia and
      hyperlipidaemia.

PMID- 9635105
TI  - Biochemical markers of acute myocardial infarction: strategies for improving
      their clinical usefulness.
AB  - We investigated the early diagnostic utility, including incremental value, of the
      serum cardiac markers creatine kinase (CK), CK-MB (mass and activity
      measurements), cardiac troponin T, and myoglobin in the diagnosis of acute
      myocardial infarction (AMI) in patients presenting to a major teaching hospital
      with chest pain and non-diagnostic electrocardiographs (ECG). The reference
      diagnosis of acute myocardial infarction was made by a single, independent
      cardiologist using World Health Organization criteria. CK and CK-MB mass were the
      only significant predictors of AMI at presentation to the Emergency Department.
      Logistic regression analysis revealed that CK did not significantly predict (P =
      0.23) myocardial infarction once CK-MB mass was in the model. Using test results
      on follow up, in addition to presentation CK-MB mass, change in CK-MB mass was
      the only other significant independent predictor of AMI. Likelihood ratios for
      various levels of the significant markers in the logistic regression are given.
      In conclusion, CK-MB mass measurement was the only useful serum cardiac marker
      for the diagnosis of AMI in patients presenting with chest pain with non
      diagnostic ECGs.

PMID- 9635106
TI  - Tetranectin levels in patients with acute myocardial infarction and their
      alterations during thrombolytic treatment.
AB  - Tetranectin (TN), a new regulator of fibrinolysis, was studied in the plasma of
      60 patients with acute myocardial infarction (AMI) and 30 healthy subjects (HS),
      in relation to D-dimer (DD) and alpha 2-plasmin inhibitor (alpha 2-PI), to
      investigate its possible involvement in the pathophysiology of AMI. Thirty
      patients underwent thrombolytic treatment with fibrin-specific plasminogen
      activator (rt-PA) (group A); the other 30 patients, according to the exclusion
      criteria, were conventionally treated (group B). Twenty of the thrombolysized
      patients established early recanalization (subgroup A1), while 10 failed to
      respond to thrombolytic treatment (subgroup A2). Median (interquartile range),
      baseline plasma TN levels were lower in AMI patients compared to HS [8.27 (2.75)
      mg/L versus 12.1 (0.55) mg/L, P < 10(-6)]. In subgroup A1, TN increased at the
      end of rt-PA infusion and returned to the baseline levels 12 h later. A positive
      association between DD and TN release (3 h level minus baseline level) was found
      (rs = 0.48, P = 0.03) in subgroup A1. No significant alterations of TN levels
      were observed during therapy in subgroup A2 and group B. TN, DD and alpha 2-PI
      concentrations in group B remained relatively constant during the study period.
      This study provides evidence of a significant decrease of TN levels in AMI
      patients compared to healthy subjects and of a remarkable difference in the
      evolution of TN levels during thrombolytic treatment with rt-PA between
      recanalized and non-recanalized AMI patients. Thus, an involvement of TN in the
      formation and dissolution of fibrin clot in AMI patients is worthy of further
      investigation.

PMID- 9635107
TI  - Apo A-I and apo E concentrations in cerebrospinal fluids of patients with acute
      meningitis.
AB  - It has been demonstrated that apolipoproteins found in cerebrospinal fluid (CSF)
      play an important role in lipid metabolism in the central nervous system (CNS).
      Previously we reported that CSF apo A-I levels increased with the severity of
      neurological damage in poliovirus-infected macaques. In the present study, apo A
      I was quantitatively analysed in CSF from patients with or without neurological
      diseases. In controls, CSF apo A-I level was significantly higher in males; 3.83
      (0.40) mg/L, mean (SEM) (n = 19) compared with females, 2.42 (0.26) mg/L (n = 23,
      P < 0.05). CSF apo A-I concentrations in patients with acute meningitis increased
      at the active stage, 7.74 (1.78) mg/L (n = 10), but returned to basal
      concentrations at the convalescent stage 2.72 (0.38) mg/L (n = 10), while the CSF
      apo A-I level in patients with other neurological diseases remained in the same
      range as in controls. By contrast, CSF apo E was consistently elevated at either
      stage of acute meningitis. Furthermore, it was found that the levels of CSF apo A
      I, but not of apo E, correlated positively with CSF albumin concentrations. These
      findings suggest that the CSF apo A-I and apo E have different origins and may
      play different roles in the lipoprotein metabolism in CNS.

PMID- 9635108
TI  - Globin chains analysis: improved resolution by electrophoresis in urea-acetic
      acid-Triton X-100.
AB  - To improve the resolution and rapidity of globin chains separation, we have
      modified the basic technique of globin chain electrophoresis in urea-acetic acid
      Triton X-100. Haemolysates from anticoagulated cord or adult blood samples were
      submitted to urea-acetic acid-Triton X-100 polyacrylamide gel electrophoresis
      using a 15% polyacrylamide gel cast in a mini slab cell which allows a rapid
      analysis of globin chains samples. After staining proteins with Coomassie
      brilliant blue R-250, the relative amounts of globin chains were determined by
      scanning. This new procedure has allowed us to obtain a better separation of the
      normal and abnormal globin chains than described previously. All the normal
      globin chains, i.e. A gamma, G gamma, delta, beta and alpha, are well separated
      by this modified technique. Semi-quantification of the G gamma/A gamma ratio has
      been performed. This simple and rapid method is also suitable for the global
      identification of the globin chain involved in the most common abnormal
      haemoglobin variants, except beta-S.

PMID- 9635109
TI  - Comparison of the Bio-Rad Porphyrin Column Test with a simple spectrophotometric
      test for total urine porphyrin concentration.
AB  - We compared two screening methods for increased urine porphyrin concentration and
      compared the results with a high-performance liquid chromatography (HPLC) method.
      The screening methods were the Bio-Rad (Porphyrin) Column Test and a simple
      spectrophotometric method. Results were obtained for urines with three different
      porphyrin patterns. Both screening methods were easy to perform. The accuracy and
      precision of the spectrophotometric method were both slightly better than that of
      the Bio-Rad Column Test. Recovery measurements in samples with different
      porphyrin patterns varied between 73% and 59% (n = 12) for the spectrophotometric
      method and between 82% and 116% (n = 12) for the Bio-Rad Column Test as compared
      to HPLC. Between batch precision measurements revealed coefficients of variation
      for spectrophotometric and Bio-Rad methods for 2%-4% and 4%-10%, respectively.
      The recovery of the porphyrins illustrates the Bio-Rad Column Test to be more
      susceptible to variation in urine porphyria composition. Both methods will show
      satisfactory results in cases of overt porphyria because of the high urine
      porphyrin concentration.

PMID- 9635110
TI  - The ratio of erythrocyte zinc-protoporphyrin to protoporphyrin IX in disease and
      its significance in the mechanism of lead toxicity on haem synthesis.
AB  - Protoporphyrin and zinc-protoporphyrin were measured in the erythrocytes of
      normal subjects, workers exposed to lead and patients with iron deficiency and
      erythropoietic protoporphyria (EPP). Results showed significantly higher levels
      of zinc-protoporphyrin in the lead-exposed workers (P < 0.0001), patients with
      iron deficiency (P < 0.0001) and EPP patients (P < 0.001) compared with normal
      subjects. The lead-exposed workers showed the highest levels of zinc
      protoporphyrin, which were significantly greater than both the iron-deficient and
      EPP patients (P < 0.0001). They also showed a higher ratio of zinc-protoporphyrin
      to free protoporphyrin compared with normal subjects (P < 0.0001) but no
      significant difference in this ratio was found when compared with iron-deficient
      patients (P = 0.1). These results are discussed in light of the controversy
      concerning the mechanism of formation of zinc-protoporphyrin in lead exposure.

PMID- 9635111
TI  - Dietary treatment of hypercholesterolaemia: lack of relationship between
      individual response and genetic variation at the lipase loci. The Fluvastatin
      Genotyping Group.
AB  - The individual benefits of dietary therapy for hyperlipidaemia are known to be
      unpredictable. Variants at the lipoprotein lipase gene have been shown to
      associate with atherogenic lipoprotein phenotypes and the delayed clearance of
      triglyceride-rich lipoproteins. Together with variants of the closely homologous
      hepatic lipase gene, these may influence the extent of amelioration of plasma
      lipoprotein concentrations seen in dyslipidaemic patients treated with a low
      saturates/low cholesterol diet. We correlated the lipid changes seen following an
      8-week diet in 83 subjects with primary hypercholesterolaemia (fasting plasma
      cholesterol > 6.5 mmol/L) with alleles of three restriction polymorphisms (LPL
      Hind III and Pvu II; HL-Msp I). Although dietary changes produced a significant
      improvement in fasting lipids [total cholesterol falling by 5.2% (range -27.9% to
      +24.3%) and low-density lipoprotein cholesterol reduced by 6.0% (-30.5% to
      +29.3%)], no significant difference in response between different genotypes could
      be detected.

PMID- 9635112
TI  - Increased gamma-glutamyltransferase in hypertriglyceridaemia: the value of
      carbohydrate-deficient transferrin measurement.

PMID- 9635113
TI  - Albumin concentration is underestimated in frozen urine.

PMID- 9635114
TI  - Audit of the clinical utility of antibodies to endomysium and gliadin as markers
      of coeliac disease.

PMID- 9635115
TI  - A simple method for the detection of lactate dehydrogenase isoenzymes M:H ratio
      by gel filtration.

PMID- 9635117
TI  - What is the best formula for predicting osmolar gap?

PMID- 9635116
TI  - A case of factitious hypocalcaemia.

PMID- 9635118
TI  - Preclinical biology of recombinant human hemoglobin, rHb1.1.
AB  - Historically, the development of hemoglobin based oxygen carriers, HBOCs, were
      confounded by issues related to activation of the complement cascade and other
      inflammatory processes, renal toxicity, and significant systemic
      vasoconstriction. However, with shortages in the blood supply, the risk of
      infectious agent contamination, and delays associated with complete crossmatch as
      well as transfusion reactions, HBOC development has assumed greater importance. A
      successful HBOC in addition to having favorable oxygen binding parameters and
      colloid oncotic properties, must also have a low toxicity profile, be
      nonimmunogenic, have positive rheologic properties, and have an adequate in vivo
      half life. In addition, it must also be stable in vivo and not undergo
      significant oxidation to methemoglobin or release heme or iron in the
      vasculature. The preclinical studies which have been designed and executed to
      address these requirements for recombinant human hemoglobin rHb1.1 serve as the
      focus of this review. Recombinant Hb1.1 represents the first HBOC to enter
      clinical trials as a recombinant product in distinction to other HBOCs which are
      derived from bovine or outdated human blood. While currently in phase II clinical
      trials, the preclinical biology which has increased our understanding of this
      molecule are the subject of this review.

PMID- 9635119
TI  - Perfluorocarbon induced alterations in pulmonary mechanics.
AB  - Perfluorocarbon (PFC) compounds induce pulmonary hyperinflation and respiratory
      distress in some animals following intravenous administration. This study was
      designed to quantify the effects of two PFC emulsions on lung volumes and
      compliance and to identify the mechanism of pulmonary hyperinflation. New Zealand
      White rabbits received isotonic saline (3 ml/kg), Fluosol (15 ml/kg) or Oxygent
      (90% perfluorooctyl-bromide emulsion, 3 ml/kg). After seven days we measured
      functional residual capacity, vital capacity, lung compliance and thoracic gas
      volume. Gross and microscopic histologic examination of the lungs was performed.
      Functional residual capacity after Fluosol administration was 16.0 +/- 4.0 ml/kg,
      significantly greater than after saline (3.4 +/- 1.0 ml/kg) or Oxygent (4.0 +/-
      1.4 ml/kg). Vital capacity was lower with Fluosol (30 +/- 5.0 ml/kg) than after
      saline (37 +/- 3.0 ml/kg) or Oxygent (37 +/- 2.0 ml/kg). Thoracic gas volume
      increased from 9 +/- 1.0 ml/kg (saline) to 16 +/- 13 ml/kg (Oxygent) and 33 +/-
      7.0 ml/kg (Fluosol). Lung compliance was the same after saline (1.6 +/- 0.5 ml.cm
      H2O-1.kg-1) and Oxygent (1.5 +/- 0.3 ml.cm H2O-1.kg-1) but lower after Fluosol
      (0.9 +/- 0.1 ml.cm H2O-1.kg-1). Gross pathology demonstrated foam exudation from
      airways of animals receiving PFCs and intra-alveolar foam was identified by light
      microscopy. These results show intra-airway foam formation causes gas trapping
      and shifts tidal breathing to a less compliant region of the pressure-volume
      curve.

PMID- 9635120
TI  - Influence of sepsis on the plasma elimination pharmacokinetics of diaspirin
      crosslinked hemoglobin in rats.
AB  - Septic shock is characterized by abnormalities in microcirculatory O2 delivery
      (QO2) and profound tissue O2 debt. Administration of crosslinked hemoglobin may
      be a means of augmenting the QO2 and tissue O2 availability. Sepsis is associated
      with hemodynamic and metabolic alterations which may affect the pharmacokinetics
      of crosslinked hemoglobin. The objective of this study was to determine the
      effect of sepsis on the plasma elimination of diaspirin crosslinked hemoglobin
      (DCLHb). Twenty-four hours after the induction of sepsis by cecal ligation and
      perforation, septic (n = 9) and sham rats (n = 8) received an intravenous
      infusion of 300 mg of DCLHb and arterial blood samples were taken at regular
      intervals to determine free plasma hemoglobin concentration. DCLHb elimination in
      septic and sham rats was consistent with first-order elimination kinetics. The
      half life (t1/2) for septic rats was 4.2 +/- 0.7 h and was significantly shorter
      than the t1/2 of non-septic rats (5.4 +/- 0.9 h). In all rats, free plasma
      hemoglobin returned to basal levels by 24 hours after DCLHb administration. The
      volume of distribution for DCLHb in the septic and non-septic rats was not
      significantly different and suggests that DCLHb is not influenced by altered gut
      permeability. Despite significant changes in some elimination parameters the
      differences were small. Consequently, dosing regimens for this compound may not
      need to be altered in sepsis.

PMID- 9635121
TI  - Accuracy of fluorocrit in determination of blood perflubron concentration.
AB  - Previous studies examining the radiosensitizing effects of perfluorochemical
      emulsions have based dose recommendations on a measurement known as fluorocrit.
      The fluorocrit is the proportion of blood volume occupied by perfluorochemicals
      and is measured using standard hematocrit procedures. This measurement is
      inherently crude and subject to error and variability between different
      individuals measuring the same sample. Furthermore, the fluorocrit method has not
      been compared to other quantitative methods to determine its reliability. The
      purpose of this study was to compare fluorocrit measurements to those obtained by
      gas chromatographic analysis. A 90% w/v perflubron emulsion was administered to
      six normal dogs once weekly for four weeks and peripheral blood samples were
      obtained at specified time points for analysis. A total of 123 blood samples were
      analyzed by both methods. The relationship between blood fluorocrit and plasma
      perflubron concentration measured by gas chromatography was examined using
      regression models. Based on the modest predictive value (r2 = 0.3683) of the
      derived statistical model, we conclude that fluorocrit measurement is an
      inaccurate method of estimation of blood perflubron concentration. Caution must,
      therefore, be exercised when extrapolating data and dose recommendations from
      reports of studies using flurocrit as the only estimate of blood perflubron
      concentration.

PMID- 9635122
TI  - Proposition of a technique to assess the vasoactive effects of hemoglobin-based
      oxygen carrying solutions in vivo: preliminary results in the rabbit aorta.
AB  - Most of hemoglobin-based oxygen carriers (HBOCs) increase the blood pressure
      after injection in the blood stream by a mechanism involving one or more factors
      that contribute to the regulation of the vascular tone. Many techniques make it
      possible to study the vascular effects of HBOCs both in vivo and in vitro. The in
      vivo methods assess the blood pressure and some estimated regional blood flows
      (use of radioactive or colored microspheres). Measurements of the real vessel
      diameter and blood flow would be useful to understand hemoglobin-mediated
      vasoconstriction mechanism. Our purpose was to elaborate an experimental model in
      anesthetized rabbits to monitor the diameter and the blood flow velocity in the
      same vessel in order to calculate the absolute blood flow. The blood flow
      velocity (in cm/s) was assessed by pulsed Doppler velocimetry and the diameter
      (in mm) was assessed by a technique of Wall Tracking. The first results indicate
      that the method is well adapted to study the effects of resuscitative fluids
      (plasma and blood substitutes) on the aorta vascular tone after hemodilution or
      resuscitation from severe hemorrhage.

PMID- 9635123
TI  - In vitro osteoinduction of demineralized bone.
AB  - Among numerous available materials for osseous repair and reconstruction, those
      presenting osteoinductive characteristics and promoting bone regeneration are
      preferable. Fresh autologous bone is one of the most effective, but it has some
      disadvantages and risks. Demineralized bone matrix (DBM) is considered to be a
      valid alternative, because it seems to show osteogenic potential, ascribed to the
      presence of bone morphogenetic proteins. In addition it can be prepared without
      difficulty and preserved without losing osteoinductive properties. The aim of the
      study was to evaluate the osteoinductive ability of xenogenic DBM, by testing DBM
      powder obtained from rabbit long bones, in cell culture of murine fibroblasts,
      alone or associated with electromagnetic field (EMF), that are known to exhibit
      biologic effects on cells: in particular they are used in orthopedics to improve
      bone formation. At the end of experiment, alkaline phosphatase (ALP) activity,
      calcium levels and cell proliferation and morphology were evaluated. A
      statistically significant stimulation of ALP activity and cell proliferation and
      a morphological change of fibroblasts were found. The results obtained show how
      DBM and EMF have different effects on cells, and that together they have synergic
      action toward bone induction.

PMID- 9635124
TI  - Preparation of highly purified hemoglobin by affinity elution.
AB  - The large scale production of recombinant hemoglobin (Hb) from microorganism or
      transgenic hosts for Hb-based blood substitutes places utmost emphasis on purity.
      In the present study, a high-resolution, convenient and inexpensive purification
      method is developed for purification of Hb from mixtures containing E. coli
      extract and bovine serum. This method is based on affinity elution by
      pyrophosphate (PPi) of Hb adsorbed on an FPLC column of the anion exchanger
      Toyopearl DEAE-650M. Compared to pH elution or NaCl elution, PPi elution makes
      possible the preparation of Hb of much higher purity. A procedure combining pH
      elution and PPi elution sequentially using a single column proves particularly
      valuable. The purification method is also applicable to the purification of
      cyanomet-Hb (CNHb+).

PMID- 9635125
TI  - Thyroid hormone, all-trans retinoic acid, and 9-cis retinoic acid functioned as
      negative modulators of the effect of glucocorticoid on induction of alpha 1-acid
      glycoprotein mRNA in RLN-10 cells.
AB  - The expression of acute-phase protein genes is controlled by many factors, such
      as IL-1, IL-6, glucocorticoids, thyroid hormone (T3), and retinoic acids. We
      studied the interaction of T3, glucocorticoids, all-trans retinoic acid (RA), and
      9-cis retinoic acid (9cRA) on the expression of the rat alpha 1-acid glycoprotein
      (AGP) gene in vitro. Dexamethasone (Dex) activated AGP gene expression in a rat
      liver derived cell line, RLN-10. Although T3, RA, and 9cRA by themselves had no
      effect on AGP production, they reduced the response to Dex of the AGP gene.

PMID- 9635126
TI  - Free radical scavenging activity of fermented papaya preparation and its effect
      on lipid peroxide level and superoxide dismutase activity in iron-induced
      epileptic foci of rats.
AB  - Fermented papaya preparation is a natural health food that has been commercially
      sold in Japan for 2 years. It is made by yeast fermentation of Carica Papaya
      Linn. We examined the antioxidant action of the fermented papaya preparation on
      free radicals and lipid peroxidation. Free radicals have been related with aging
      and diseases, such as cancer, diabetes and especially in neurological disorders,
      for example, Parkinson's disease or Alzheimer's disease. A diet including
      variable antioxidant foods may therefore help to prevent these illnesses. The
      free radical scavenging activity of the fermented papaya preparation was examined
      using an electron spin resonance (ESR) spectrometer. Fermented papaya preparation
      (50 mg/ml) scavenged 80% of hydroxyl radicals (.OH) as spin adducts of spin trap,
      5,5-dimethyl-1-pyrroline-N-oxide (DMPO) (5.27 x 10(15)spins/ml) generated by
      Fenton reagents. The value of IC50 was 12.5 mg/ml. The oral administration of the
      fermented papaya preparation for 4 weeks decreased the elevated of lipid peroxide
      levels in the ipsilateral 30 min after injection of iron solution by iron into
      the left cortex of rats. The fermented papaya preparation also increased
      superoxide dismutase activity in the cortex and hippocampus of them. These
      results suggest that the fermented papaya preparation has antioxidant actions and
      that it may be prophylactic food against the age related and neurological
      diseases associated with free radicals.

PMID- 9635127
TI  - Effects of ethanol ingestion on insulin binding to rat Leydig cells.
AB  - Effects of ethanol treatment and its withdrawal on insulin binding to isolated
      rat Leydig cells were studied. Mature rats were given ethanol by gastric
      intubation for 30 days at a dose of 3.0 g/kg body weight, twice daily, as a 25%
      (v/v) aqueous solution and treatment was withdrawn for the subsequent 30 days in
      an another group. Ethanol treatment markedly increased serum insulin and reduced
      the 125I-insulin binding to Leydig cells and the activities of Leydig cellular
      steroidogenic enzymes such as 3 beta-HSD and 17 beta-HSD. Withdrawal of ethanol
      treatment restored these changed values to their normal levels. The results
      suggest the possible involvement of subnormal insulin actions, as that of LH, in
      the ethanol-induced impairment of Leydig cellular steroidogenesis and the
      resulting hypoandrogenization associated with alcohol abuse.

PMID- 9635128
TI  - Attenuated antigenicity of ribonucleoproteins modified by reactive oxygen
      species.
AB  - Ribonucleoprotein (RNP) particles isolated from fresh goat liver nuclei were
      exposed to hydroxyl radical which induced modification in the gross structure of
      RNP particles. To evaluate the effect of hydroxyl modification on the antigenic
      properties of RNP and possible role of ROS-RNP in the initiation and development
      of SLE, enzyme immunoassays were carried out. SLE sera having high titre anti-DNA
      antibodies showed enhanced binding to hydroxyl modified RNP particles in
      comparison to unmodified RNP particles. In competition assay none of the SLE sera
      or isolated IgG showed preference for ROS-modified RNP particles over native RNP
      particles. These studies suggest that anti-RNP autoantibodies observed in
      subpopulation of SLE patients are generated by some other intra-or extracellular
      mechanisms and hydroxyl radical has probably no direct role in the initiation of
      antibodies.

PMID- 9635129
TI  - Influence of phenoxyherbicides and their metabolites on the form of oxy- and
      deoxyhemoglobin of vertebrates.
AB  - The effect of phenoxyherbicides and their metabolites on the structure of oxy-
      and deoxyhemoglobin was studied by using different doses and times of incubation
      of hemoglobin with the herbicide. It was ascertained that among the investigated
      hemoglobins the most sensitive was carp oxyhemoglobin incubated with 2,4-D (2,4
      dichlorophenoxyacetic acid) and the least sensitive was human hemoglobin.
      Comparing the toxicity of 2,4-D, MCPA (2-methyl-4-chlorophenoxyacetic acid), 2,4
      DCP (2,4-dichlorophenol), 2,4-DMP (2,4-dimethylphenol) it was found that the
      highest decrease occurred in bovine hemoglobin incubated with 2,4-DMP. The
      phenoxyherbicides caused stabilization of the structure of T-deoxyhemoglobin in
      vitro, in that they decreased the oxygen affinity with a simultaneous increase in
      methemoglobin concentration.

PMID- 9635130
TI  - Reactivity of the horseradish peroxidase compounds I and II toward organometallic
      substrates. A stopped-flow kinetic study of oxidation of ferrocenes.
AB  - Reactivity of horseradish peroxidase compounds I and II (HRP-I and HRP-II) toward
      organometallicic substrates, viz water-soluble ferrocenes RFc (R = COOH and
      CH2NMe2), has been studied at 25 degrees C, pH 6.0 and ionic strength 0.1 M. The
      second-order rate constants k2 for the reaction of HRP-I with FcCOOH and
      FcCH2NMe2 equal (1.00 +/- 0.04) x 10(6) and (0.27 +/- 0.01) x 10(6) M-1 s-1,
      respectively. The values of k3 for the reaction of HRP-II with FcCOOH and
      FcCH2NMe2 equal (1.1 +/- 0.1) x 10(4) and (0.25 +/- 0.01) x 10(4) M-1 s-1,
      respectively. The steady-state kinetic study of the HRP-catalyzed oxidation of
      the ferrocenes by H2O2 under the same conditions gave the second-order rate
      constants of (0.94 +/- 0.03) x 10(4) and (0.24 +/- 0.06) x 10(4) M-1 s-1 for
      FcCOOH and FcCH2NMe2, respectively, which are in a good agreement with k3. The
      results reported here confirm the proposal that the rate-limiting step of the
      steady-state oxidation of ferrocenes is the electron transfer from the substrate
      to HRP-II.

PMID- 9635131
TI  - Starvation induced hypothyroidism involves perturbations in thyroid superoxide
      SOD system in pigeons.
AB  - This study investigated the influence of starvation over seven days on avian
      thyroidal superoxide radical levels and superoxide dismutase activity profiles in
      the Indian rock pigeon Columba livia intermeida, in relation with iodine
      metabolism. The serum thyroid hormone profile was assayed to correlate the
      thyroidal redox status with the circulating thyroid hormone levels. The spin
      trapping results suggest a role for thyroidal superoxide anion (O2.-) in causing
      a hypothyroid state in pigeons during long term energy withdrawal. Pigeons
      starved for 1 day generated superoxide and iodide free radicals in their
      thyroids, with a significant decrease in SOD activity. Regain of SOD activity in
      2nd- and 3rd-day starved birds is marked by complete scavenging of radicals in
      the thyroid, suggesting the significance of SOD in thyroid glands as a potential
      antioxidant sink against reactive oxygen species, O2.- Resurgence of O2.-
      radicals with a parallel decrease in SOD activity in the thyroid gland on 5th-
      and 7th-day of starvation provides evidence of disruption of homeostasis between
      pro-oxidant and antioxidant states, leading to oxidative stress in avian thyroid
      during long-term calorie crisis. Following starvation both thyroid hormones
      thyroxine (T4) and triiodothyronine (T3) decreased, putting pigeons in a
      hypothyroid state. We argue that oxidative inactivation of thyroid peroxidase and
      other thyroid proteins by radical attack during starvation invoked oxidative
      stress, which could be one of the factors responsible for the hypothyroid state
      in pigeons.

PMID- 9635132
TI  - Reductive dechlorination of DDT to DDD by rat blood.
AB  - The present study provides evidence that the reductive dechlorination of DDT (p,
      p'-dichlorodiphenyltrichloroethane) to DDD (p, p'-dichlorodiphenyldichloroethane)
      mediated by rat blood proceeds in the presence of both a reduced pyridine
      nucleotide and a flavin. The reduction appears to proceed in two steps. The first
      step is reduction of a flavin such as FAD, FMN or riboflavin by NADPH or NADH,
      either enzymatically or nonenzymatically. The second step is nonenzymatic
      reductive dechlorination of DDT by the reduced flavin, catalyzed by the heme
      group of hemoglobin.

PMID- 9635133
TI  - Hormone-induced changes in cardiolipin from Leydig cells: possible involvement in
      intramitochondrial cholesterol translocation.
AB  - The rate-limiting and hormonally regulated step in steroid hormone biosynthesis
      is the delivery of cholesterol from the outer to the inner mitochondrial membrane
      where cytochrome P450scc resides. Although the exact mechanism of
      intramitochondrial cholesterol translocation remains unknown, the formation of
      contact sites between outer and inner mitochondrial membranes appears as a
      necessary component for cholesterol transfer. Several pieces of evidence suggest
      that local formation of intermembrane contact is a consequence of a non-bilayer
      arrangement of polymorphic lipids which are enriched in the junctions. As a step
      toward clarifying mitochondrial contact sites formation and thus cholesterol
      translocation in steroidogenic cells, we have undertaken studies to identify the
      factors which might result in non-bilayer structure to be adopted by
      mitochondrial phospholipids on stimulation of MA-10 Leydig cells. Our results
      demonstrate that an increase in the unsaturation of the cardiolipin acyl groups
      on hormonal stimulation might favor the formation of non-bilayer adhesion points.

PMID- 9635134
TI  - Nucleotide sequence and intergeminiviral homologies of the DNA-A of papaya leaf
      curl geminivirus from India.
AB  - Coat protein gene, rep protein gene and intergenic region of the genome of a
      whitefly transmitted geminivirus (WTG) causing severe leaf curl in papaya plants
      were PCR amplified, cloned and sequenced. Comparison of the amino acid sequence
      of the putative coat protein product of papaya leaf curl virus (PLCV) with some
      other mono and bipartite WTGs revealed a maximum of 89.8% homology with Indian
      cassava mosaic virus. The genomic organization of PLCV-India is similar to other
      WTGs with bipartite genomes. Comparison of the coat protein N-terminal 70 amino
      acid sequence (and other biological features) of PLCV with other geminiviruses
      shows that PLCV is a distinct geminivirus from India and is related to WTGs from
      the old world.

PMID- 9635135
TI  - Lucigenin reduction by NADPH-cytochrome P450 reductase and the effect of
      phospholipids and albumin on chemiluminescence.
AB  - To assess lucigenin, a chemilumigenic probe, as a detector of superoxide anion in
      microsomes, NADPH oxidation, lucigenin disappearance, and chemiluminescence in a
      system including purified NADPH-cytochrome P450 reductase were examined. NADPH
      oxidation was increased by adding lucigenin, and concurrently, its disappearance
      and oxygen consumption were also stimulated. Chemiluminescence, which is
      negligibly emitted in the presence of the reductase alone, was remarkably
      amplified with phospholipids and albumin. Menadione inhibited lucigenin
      disappearance resulting in suppression of chemiluminescence. Lucigenin
      chemiluminescence measured in microsomes appears not to reflect direct superoxide
      anion production from microsomal components and from quinones, such as menadione.

PMID- 9635136
TI  - Soluble guanylate cyclase in Saccharomyces cerevisiae.
AB  - After removing nonspecific immunoreactivities from crude extract by
      immunoaffinity chromatography, an immunoreactive-band at 40kDa of soluble
      guanylate cyclase (SGC) from Saccharomyces cerevisiae was detected by Western
      blot using rabbit anti-beta 1 subunit of SGC. Cyclic GMP level and SGC activity
      was measured by ELISA. Immunoprecipitated yeast SGC was activated by sodium
      nitroprusside, whereas inhibited by 1H-(1,2,4)oxadiazolo(4,3-A)quinoxalin-1-one.
      Increased cyclic GMP level was also noted when intact yeast cells were incubated
      with s-nitrosoglutathione, a NO donor. The result implies that NO can be utilized
      intracellularly and extracellularly. Moreover, the presence of SGC suggests the
      significance of NO/cyclic GMP signaling in unicellular eukaryotes.

PMID- 9635137
TI  - Methionine modification impairs the C5-cleavage function of cobra venom factor
      dependent C3/C5 convertase.
AB  - The complement-mediated lysis of guinea pig erythrocytes by cobra venom factor
      (CVF) decreased by 50-60% within 2 min of treatment with 5 mM sodium periodate at
      0 degree C. This loss of activity paralleled modification of 3-4 Met; other amino
      acids and sugar residues of the oligosaccharide chains were not affected.
      Treatment with N-chlorosuccinimide or chloramine-T under conditions that
      specifically modified 3-4 readily-oxidizable Met also caused 50-60% loss of CVF
      activity. The secondary structure of CVF was not altered by these modifications.
      Methionine-modified CVF (MetCVF) supported the cleavage of factor B by factor D
      with equal efficiency as that of untreated CVF to form C3/C5 convertase
      (MetCVF,Bb) of the alternative pathway. MetCVF,Bb and CVF,Bb were
      indistinguishable with respect to C3 cleavage. However, the C5-cleavage ability
      of MetCVF,Bb was significantly lower than that of CVF,Bb. These results suggest
      the involvement of Met in CVF binding of C5.

PMID- 9635138
TI  - DNA methylation by wheat cytosine DNA methyltransferase: modulation by protease
      inhibitor E-64.
AB  - Cytosine DNA methyltransferase isolated from wheat seedlings and purified in the
      presence of metalloprotease and serine protease inhibitors has molecular mass and
      specific activity equal to about 85 kDa and 250 units/mg protein, respectively.
      Apparent K(m) for AdoMet and [I]50 for AdoHcy values are about 6 microM and 12
      microM, respectively. The enzyme is active in wide pH range (pH 5.5-8.5) and is
      inhibited by NaCl. The enzyme rapidly loses its methyltransferase activity in the
      absence of substrates. Using the cysteine protease inhibitor E-64 it has been
      shown that rapid enzyme inactivation is caused by disappearance of essential
      enzyme SH-groups but is not due to proteolytic enzyme cleavage.

PMID- 9635139
TI  - A novel method for selection of chymotrypsin inhibitors from a phage peptide
      library.
AB  - A novel screening strategy has been developed for the identification of alpha
      chymotrypsin inhibitors from a phage peptide library. In this strategy, the
      standard affinity selection protocol was modified by adding a proteolytic
      cleavage period to avoid recovery of alpha-chymotrypsin substrates. After four
      cycles of selection and further activity assay, a group of related peptides were
      identified by DNA sequencing. These peptides share a consensus sequence motif as
      (S/T)RVPR(R/H). Then, a corresponding short peptide (Ac-ASRVPRRG-NH2) was
      synthesized chemically and proved to be an inhibitor of alpha-chymotrypsin. The
      present work provides a useful way for searching proteinase inhibitors without
      detailed knowledge of the molecular structure.

PMID- 9635140
TI  - The prevention of carbon tetrachloride-induced hepatotoxicity in mice by alpha
      hederin: inhibiton of cytochrome P450 2E1 expression.
AB  - The protective effects of alpha-Hederin on carbon tetrachloride-induced
      hepatotoxicities were investigated in mice. Pretreatment with alpha-Hederin prior
      to the administration of carbon tetrachloride significantly prevented the
      increase in serum alanine aminotransferase (ALT) and lactate dehydrogenase (LDH)
      activity and lipid peroxidation in a dose dependent manner. Hepatic glutathione
      levels and glutathione-S-transferase activities were not affected by pretreatment
      with alpha-Hederin alone but pretreatment with alpha-Hederin protects carbon
      tetrachloride-induced depletion of hepatic glutathione levels. The effects of
      alpha-Hederin on the cytochrome P450 (P450) 2E1, the major isozyme involved in
      carbon tetrachloride bioactivation were investigated. alpha-Hederin markedly
      decreased the P450 2E1-specific activities of p-nitrophenol and aniline
      hydroxylation in a dose-dependent manner. Consistent with these observations, the
      P450 2E1 expressions were also decreased, as determined by immunoblot analysis.
      These results demonstrate that treatment of mice with alpha-Hederin decreases the
      expression and activities of P450 2E1 enzyme, and reduces biotransformation of
      carbon tetrachloride, and diminished carbon tetrachloride-induced liver injury.

PMID- 9635141
TI  - Hydrogen peroxide-supported activities of semisynthetic flavocytochrome 2B4.
AB  - Semisynthetic flavocytochromes, obtained by covalent binding of riboflavin with
      cytochromes P450 2B4, were able to catalyze the H2O2-mediated reactions of
      aniline p-hydroxylation, aminopyrine N-demethylation and p-nitroanizole' O
      dealkylation. The rates of the flavocytochrome-catalyzed, H2O2-supported
      reactions far exceeded those of the appropriate NADH-dependent reactions and were
      comparable with the cytochrome P450 2B4-catalyzed, peroxide-mediated reaction
      rates. The kinetic parameters (kcat, K(m)) for the peroxide-dependent
      flavocytochrome P450 2B4 reactions were obtained. Sodium cyanide and SKF-525A, a
      specific P450 inhibitor, were both shown to inhibit these reactions. The
      generation of active oxygen species by flavocytochrome 2B4 was registered by
      chemiluminescence intensity.

PMID- 9635142
TI  - A novel rapid-reaction spectrophotometric method for monitoring monovalent anion
      exchange by human erythrocyte band 3.
AB  - Thiocyanate (SCN-) uptake into human erythrocytes and resealed ghosts was
      measured by monitoring the intracellular reaction of SCN- with methemoglobin
      using a dual wavelength stopped-flow apparatus. The cellular reaction was
      considerably slower than the reaction of SCN- with methemoglobin in solution,
      indicating that SCN- diffusion and not chemical reaction was rate limiting. This
      view was confirmed by showing that the uptake rate followed saturation kinetics
      (K(m) approximately 9 mM), thus indicating that SCN- transport involves a
      facilitated diffusion process. Addition of DIDS (4,4'-diisothiocyanatostilbene
      2,2'-disulfonate) totally inhibited SCN- uptake, thus identifying band 3 as the
      sole facilitator. Substitution of iodide or sulfate for trans chloride, slowed
      SCN- uptake by 4-fold and 35-fold respectively. Reducing the trans chloride
      concentration from 150 to 2 mM decreased the extent of the reaction, and slowed
      the observed rate by about 2-fold. These results define a new approach for the
      continuous monitoring of monovalent anion exchange by human erythrocyte band 3.

PMID- 9635143
TI  - Luminol luminescence induced by oxidants in antioxidant-deficient yeasts
      Saccharomyces cerevisiae.
AB  - Luminol chemiluminescence induced in the presence of yeast cells and yeast cell
      homogenates was significantly induced by exogenous oxidants (hydrogen peroxide
      and menadione). tert-Butyl hydroperoxide did not stimulate chemiluminescence by
      itself but augmented menadione-induced chemiluminescence. Comparison of yeast
      strains deficient in catalase, superoxide dismutase or glutathione showed that
      only glutathione-deficient strains showed elevated chemiluminescence in this
      system. These results support the idea that more reactive species than hydrogen
      peroxide and superoxide are critical in the induction of luminol
      chemiluminescence.

PMID- 9635144
TI  - Cloning and sequencing of the cDNA coding for pig pre-uteroglobin/Clara cell 10
      kDa protein.
AB  - Using reverse transcription-polymerase chain reaction (RT-PCR) on pig lung mRNAs,
      we have cloned and sequenced an almost full-length complementary DNA (cDNA)
      coding for pig pre-uteroglobin/Clara cell 10 kDa protein (UG/CC10), a major
      secretory protein of lung Clara cells. The deduced amino acid sequence indicated
      a preprotein of 91 residues, 21 of which corresponded to the signal peptide.
      Comparison of the sequence with those of known pre-UG/CC10 from other species
      indicated that the pig protein resembles the structure shared by human and
      Lagomorpha pre-UG/CC10 but differ from the proteins from Rodentia that are
      composed of 96 aminoacids and contain signal peptides of 19 residues. Some amino
      acids, that form part of a hydrophobic pocket inside the mature protein, are well
      conserved in all UG/CC10 suggesting an important function of this cavity.
      Northern analysis indicated that pig UG/CC10 mRNA is abundant in lung but is not
      detectable in liver, uterus or epididymis. The results are discussed in relation
      to a possible physiological function of UG/CC10.

PMID- 9635145
TI  - The 1997 Stevenson Award Lecture. Cardiac K+ channel gating: cloned delayed
      rectifier mechanisms and drug modulation.
AB  - K+ channels are ubiquitous membrane proteins, which have a central role in the
      control of cell excitability. In the heart, voltage-gated delayed rectifier K+
      channels, like Kv1.5, determine repolarization and the cardiac action potential
      plateau duration. Here we review the broader properties of cloned voltage-gated
      K+ channels with specific reference to the hKv1.5 channel in heart. We discuss
      the basic structural components of K+ channels such as the pore, voltage sensor,
      and fast inactivation, all of which have been extensively studied. Slow, or C
      type, inactivation and the structural features that control pore opening are less
      well understood, although recent studies have given new insight into these
      problems. Information about channel transitions that occur prior to opening is
      provided by gating currents, which reflect charge-carrying transitions between
      kinetic closed states. By studying modulation of the gating properties of K+
      channels by cations and with drugs, we can make a more complete interpretation of
      the state dependence of drug and ion interactions with the channel. In this way
      we can uncover the detailed mechanisms of action of K+ channel blockers such as
      tetraethylammonium ions and 4-aminopyridine, and antiarrhythmic agents such as
      nifedipine and quinidine.

PMID- 9635146
TI  - Extravascular adenosine influences endothelium-derived nitric oxide release from
      perfused dog semitendinosus artery.
AB  - We tested the hypothesis that extravascular adenosine induces the release of
      vasodilatory products from endothelial cells lining skeletal muscle vessels.
      Endothelium-intact (n = 35) and -denuded (n = 5) dog semitendinosus intramuscular
      arteries were isolated, cannulated, and placed in 100-mL baths containing Krebs
      Henseleit bicarbonate buffer (Krebs) at 37 degrees C and gassed with 95% O2--5%
      CO2. Each vessel, as well as a parallel tubing segment (avascular control), was
      perfused at 3.5 +/- 0.2 mL/min (inflow pressure 94 +/- 2 mmHg; 1 mmHg = 133.3 Pa)
      with Krebs containing 100 microM phenylephrine, 6% dextran, and 15 units/mL
      superoxide dismutase. Perfusate from all segments dripped onto endothelium
      denuded dog femoral artery rings. The addition of 10 microM acetylcholine to the
      perfusate to test the functional integrity of endothelium-intact donor segments
      did not alter resistance in vessel segments or change force in rings. The
      addition of 100 microM adenosine to the extravascular bath decreased resistance
      1.5 +/- 0.4 mmHg.mL-1.min-1 in vessel segments but was without effect on
      downstream rings. When acetylcholine was retested in the presence of
      extravascular adenosine, a relaxation (16 +/- 6%) occurred in rings receiving
      perfusate from endothelium-intact segments but not endothelium-denuded or tubing
      segments. This relaxation was eliminated by N omega-nitro-L-arginine (10 microM),
      a nitric oxide synthase inhibitor, and was attenuated to 4 +/- 1% by 8
      phenyltheophylline (10 microM), an adenosine receptor antagonist. Thus adenosine,
      in conjunction with acetylcholine, acting through a receptor-mediated event,
      resulted in the release of nitric oxide from the endothelium of perfused
      intramuscular arteries, indicating the potential for extravascular conditions to
      influence the release of endothelium-derived products.

PMID- 9635147
TI  - Scavestrogen sulfamates: correlation between estrone sulfatase inhibiting and
      antioxidant effects.
AB  - In the present study estrone sulfatase (steryl-sulfatase; EC 3.1.6.2) and
      phenylsulfatase (arylsulfatase B; EC 3.1.6.1) inhibiting as well as antioxidant
      effects exerted by ring B,C unsaturated sulfamates of estrone (J 1025), 17 beta
      estradiol (J 1054, J 1059, J 1067), and 17 alpha-estradiol (J 1051, J 1064, J
      1065) were examined as compared with their parent compounds, J 994, J 995, and J
      1050, using six different in vitro models: (i) estrone sulfatase activity in
      human placental microsomes, (ii) phenylsulfatase activity isolated from Helix
      pomatia, (iii) Fenton reaction driven lipid peroxidation in rat synaptosomes,
      (iv) Fe(II)-chelating activities, (v) formation of superoxide anion radicals, and
      (vi) total antioxidative activities. Ring B,C unsaturated estrogen (so-called
      scavestrogen) sulfamates were found to act as potent inhibitors of the following
      enzyme activities and generated radicals: estrone sulfatase, phenylsulfatase,
      lipid peroxyl, and superoxide anion. In addition, scavestrogen sulfamates were
      able to influence the iron redox chemistry and total antioxidative activities.
      These findings indicate that relatively minor modifications in the chemical
      structure of classical steroid sulfamates can preserve or enhance their estrone
      sulfatase inhibiting properties and, simultaneously, amplify their antioxidant
      capacity to a great extent. Taken together, our data suggest that scavestrogen
      sulfamates such as J 1025, J 1051, or J 1054 (17 beta-dihydroequilenin sulfamate)
      may serve as a very promising basis for the development of steroid-derived
      estrone sulfate-sulfatase inhibitors characterized by promising estrone sulfatase
      inhibiting activities in combination with a "good" antioxidant potency.

PMID- 9635148
TI  - Functional effects of uridine triphosphate on human skinned skeletal muscle
      fibers.
AB  - Chemically skinned human skeletal muscle fibers were used to study the effects of
      uridine triphosphate (UTP) on the tension-pCa relationship and on Ca2+ uptake and
      release by the sarcoplasmic reticulum (SR). Total replacement (2.5 mM) of
      adenosine triphosphate (ATP) with UTP (i) displaced the tension-pCa relationship
      to the left along the abcissae and increased maximum Ca(2+)-activated tension,
      both effects being larger in slow- than in fast-type fibers; (ii) markedly
      reduced Ca2+ uptake by the SR (evaluated by the caffeine-evoked tension) in both
      fiber types; (iii) had no effect on the rate of depletion of caffeine-sensitive
      Ca2+ stores during soaking in relaxing solutions; (iv) induced tension in slow-
      but not in fast-type fibers. The effects on the SR functional properties are
      consistent with the notion that UTP is a poor substitute for ATP as a substrate
      for the Ca ATPase pump and as an agonist of the ryanodine-sensitive Ca(2+)
      release channel. The UTP-induced tension in human slow-type fibers is attributed
      to effect(s) of the nucleotide on the tension-pCa relationship of the contractile
      machinery. The present data reveal important differences between the effects of
      UTP on human versus rat muscle fibers.

PMID- 9635149
TI  - Thromboxane A2 does not act at the carotid sinus to mediate cardiovascular,
      adrenocorticotropin, cortisol, or blood gas responses.
AB  - Thromboxane A2 (TxA2), well known as a vasoconstrictor and activator of
      platelets, also stimulates reflex cardiovascular, pituitary, adrenocortical, and
      blood gas responses, although the site of action is unknown. Previously we
      determined that the site of these actions is perfused by the carotid vasculature.
      The purpose of the present study was to test the hypothesis that TxA2 stimulates
      these responses by acting at the carotid sinus. The TxA2 mimetic U46619 (1
      microgram.kg-1.min-1) or saline was infused into the carotid artery (CA) or vena
      cava in conscious, chronically instrumented carotid sinus denervated (CSD) or
      sham-operated sheep. Mean arterial pressure increased in all groups receiving
      U46619. Heart rate increased only in the CSD group receiving CA infusions of
      U46619. Adrenocorticotropic hormone (ACTH) and cortisol increased in the sham and
      CSD groups receiving CA U46619, and responses were not different between sham and
      CSD groups. PaCO2 values were higher in all CSD treatment groups compared with
      sham treatment groups. Arterial pH increased and PaCO2 decreased in both the sham
      and CSD groups in response to CA U46619. Although PaCO2 values were higher
      overall in the CSD group, the magnitude of change in response to U46619 infusions
      was similar in sham and CSD animals. There was no difference in pHa between CSD
      and sham groups. Hematocrit and PaO2 did not change. We conclude that TxA2 does
      not act at the carotid sinus, as responses to U46619 infusions in CSD animals
      were not different in the cases of ACTH, cortisol, and blood gases, or were
      enhanced rather than diminished in the case of heart rate. These findings support
      a hypothesis that TxA2 acts at the brain to mediate cardiovascular, pituitary,
      adrenocortical, and blood gas responses.

PMID- 9635150
TI  - Similarities between vasoconstrictor- and veratridine-stimulated metabolism in
      perfused rat hind limb.
AB  - The vasoconstrictors norepinephrine (NE) and angiotensin II (AII) mediate
      increases in oxygen uptake (VO2) by the constant flow perfused rat hind limb that
      are inhibited by quinidine-like membrane-stabilizing effects (involving the
      interruption of action potential) of (+/-)-propranolol with little effect on
      vasoconstriction. The membrane labilizer veratridine, 10 microM, which has the
      capability of maintaining voltage-gated Na+ channels of the plasma membrane in
      their open state, also increases VO2 but without an increase in pressure. Thus in
      the present study veratridine was characterized in detail and compared with NE in
      the same system. Veratridine (3-100 microM) produced a dose-dependent stimulation
      of VO2 (from 11.8 +/- 0.3 to 20.4 +/- 0.6 mumol.h-1.g-1 (n = 5), p < 0.0001) and
      lactate efflux (LE) (from 7.4 +/- 0.6 to 23.0 +/- 4.7 mumol.h-1.g-1 (n = 5), p <
      0.01). These increases were independent of vasoconstriction at low doses (< or =
      10 microM). At higher doses of veratridine the accompanying minor
      vasoconstriction (from 17 +/- 1 to 30 +/- 2 mmHg (1 mmHg = 133.3 Pa) (n = 5), p <
      0.005) was blocked by sodium nitroprusside (NP) while neither VO2 nor LE was
      greatly affected. Low Na+ perfusions (25 mM) did not affect the vasoconstrictor
      action of NE but markedly inhibited increases in VO2 and LE due to either
      veratridine or NE. Veratridine (10 microM) mediated increases in VO2 and LE were
      blocked by either (+/-)-propranolol (100 microM) or 150 microM quinidine. It is
      concluded that vasoconstrictors such as NE, which stimulate VO2 in the perfused
      rat hind limb, do so by a two-stage process involving an essential nitroprusside
      sensitive redirection of flow followed by a mechanism involving increased ion
      movement across skeletal muscle cell membranes, which is blocked by membrane
      stabilizers. Veratridine achieves a similar increase in VO2 but may do so by
      directly destabilizing the skeletal muscle cell membrane without the requirement
      of a redirection of flow.

PMID- 9635151
TI  - Inhibitory effects of candesartan on responses to angiotensin peptides in the
      hindquarters vascular bed of the cat.
AB  - The effects of the nonpeptide angiotensin II AT1 receptor antagonist candesartan
      on responses to angiotensin II were investigated in the hindquarters vascular bed
      of the cat. Under constant-flow conditions, injections of angiotensin II into the
      hindquarters perfusion circuit elicited dose-dependent increases in perfusion
      pressure. Candesartan in a dose of 3 micrograms/kg i.v. decreased vasoconstrictor
      responses to angiotensin II in a competitive manner. However, at doses of 10-1000
      micrograms/kg i.v., candesartan shifted the dose-response curve to angiotensin II
      to the right in a nonparallel manner, suggesting a noncompetitive blockade. The
      inhibitory effects of candesartan on responses to angiotensin II were long in
      duration, and the AT1 receptor antagonist had little effect on baseline
      pressures. Candesartan was without effect on vasoconstrictor responses to
      norepinephrine, U46619, PGF2 alpha, and BAY K8644; on biphasic responses to
      endothelin-1; and on vasodilator responses to acetylcholine. Candesartan
      significantly attenuated hindquarters vasoconstrictor responses to angiotensin
      III and IV with a parallel shift at the 3 micrograms/kg iv dose and a nonparallel
      shift to the right at the high dose of the AT1 receptor antagonist. The results
      of the present study indicate that candesartan is a potent angiotensin AT1
      receptor antagonist that can induce both competitive and noncompetitive blockade
      of responses to angiotensin II, III, and IV n the hindquarters vascular bed of
      the cat.

PMID- 9635152
TI  - Analysis of effects of bosentan (Ro 47-0203), a nonpeptide endothelin ETA/ETB
      receptor antagonist, in the hind-limb vascular bed of the cat.
AB  - The effects of bosentan (Ro 47-0203), an endothelin A and B receptor antagonist,
      on responses to endothelin-1, sarafotoxin 6c, angiotensin II, and arginine
      vasopressin were investigated in the hind-limb vascular bed of the cat. Under
      constant-flow conditions, intraarterial injections of endothelin-1 and
      sarafotoxin 6c induced biphasic changes in hind-limb perfusion pressure
      characterized by an initial decrease followed by a secondary increase in
      perfusion pressure. The vasodilator and vasoconstrictor components of the
      biphasic responses to endothelin-1 and sarafotoxin 6c were reduced by bosentan,
      and the endothelin receptor antagonist reduced baseline systemic arterial and
      hind-limb perfusion pressures. Bosentan decreased vasoconstrictor responses to
      lower doses of angiotensin II, whereas responses to higher doses of angiotensin
      II and responses to vasopressin, U46619, BAY K8644, norepinephrine,
      acetylcholine, bradykinin, levcromakalim, PGE1, adrenomedullin, and calcitonin
      gene-related peptide were not altered. Vasoconstrictor responses to ET-1 were not
      altered by the angiotensin AT1 receptor antagonist DuP 532 or the AT2 receptor
      antagonist PD123,319. The results of the present study show that bosentan
      attenuates vasodilator and vasoconstrictor responses to endothelin-1 and
      sarafotoxin 6c and vasoconstrictor responses to lower doses of angiotensin II in
      the hind-limb vascular bed of the cat. These results suggest that endothelin may
      be involved in mediating responses to lower doses of angiotensin II and in the
      maintenance of baseline tone in the systemic vascular bed of the cat.

PMID- 9635153
TI  - Changes in [K+]o evoked by baclofen in guinea pig hippocampus.
AB  - K(+)-sensitive microelectrodes were used to record changes evoked by baclofen in
      extracellular potassium concentration ([K+]o) and field potentials in the stratum
      pyramidale (SP) and stratum radiatum (SR) in the CA1b region of guinea pig
      hippocampal slices in vitro. Bath applications of (+/-)-baclofen (1 microM-3 mM
      for approximately 5 min) evoked changes in [K+]o, which were in most cases
      sustained throughout agonist application and reversed during washout. The maximal
      (Rmax) values for curves fitted to the concentration-response data were for SP
      and SR, respectively, 0.59 +/- 0.03 and 0.65 +/- 0.03 mM, and EC50 values were
      39.7 and 39.4 microM, respectively. The evoked K+ and field potential changes
      were significantly correlated and could be blocked by 2-OH-saclofen (50 microM)
      and CGP 35348 (50 microM). In < or = 10% of experiments baclofen (10-50 microM)
      induced either a decrease or a transient increase (< or = 1 min duration) in
      [K+]o; in some slices with concentrations > or = 20 microM an initial decrease
      preceded a progressive increase. Pressure ejection of baclofen (100 microM for
      100-900 ms) evoked increases in [K+]o and field potentials, which were larger in
      SR than in SP. In < or = 10% of slices brief and (or) sustained application of
      baclofen (by either bath perfusion or pressure ejection) also evoked synchronous,
      repetitive interictal and ictal discharges at frequencies approximately 1/s and
      1/12 s, respectively, an observation that affirms a proconvulsant capacity. It is
      concluded that (i) although increases in [K+]o evoked by baclofen in SR compared
      with SP are slightly larger, they are not significantly different, (ii) GABAB
      receptor subtype(s) in SR and SP appear similar, as they have identical
      affinities, and (iii) [K+]o accumulations evoked by GABA likely include a
      contribution from a GABAB receptor activated K+ conductance, especially in
      dendritic regions.

PMID- 9635154
TI  - Gentamicin uptake by LLCPK1 cells: effect of intracellular and extracellular pH
      changes.
AB  - The mechanisms by which aminoglycosides are transported across the luminal
      membrane of renal proximal tubular cells remain unclear. A luminal organic
      cation/H+ exchange as well as an adsorptive endocytosis membrane process has been
      proposed to be involved in gentamicin renal accumulation. The objectives of this
      work were to explore further the effects of intracellular and extracellular pH
      changes on gentamicin uptake. [3H]Gentamicin uptake by a continuous renal
      epithelial cell line, LLCPK1, grown as a monolayer on an impermeable surface was
      measured at different temperatures and pH conditions and in the presence of
      various inhibitors. Uptake of gentamicin was found to be carrier mediated (K(m) =
      1.26 +/- 0.22 mM, Vmax = 289 +/- 27 pmol.mg-1.min-1), energy dependent (inhibited
      in part by sodium azide), and temperature dependent (37 degrees C > 4 degrees C).
      Fifteen-minute gentamicin (10 microM) uptake was inhibited by 1 mM of the organic
      cations cimetidine (61.0%), quinidine (73.5%), quinine (68.6%), and verapamil
      (61.5%). More importantly, while an outwardly directed proton gradient did not
      have a significant effect on gentamicin uptake, extracellular acidification (pH
      6.5), which leads to a higher degree of gentamicin ionization, significantly
      enhanced gentamicin uptake by LLCPK1 monolayer cells. These results suggest that
      the luminal organic cation/H+ exchanger is not involved in gentamicin uptake by
      renal cultured epithelial cells. Rather, the cationic charge of gentamicin
      appears to be one of the primary determinants for renal luminal uptake.

PMID- 9635155
TI  - Acute effects of prolactin on passive calcium absorption in the small intestine
      by in vivo perfusion technique.
AB  - The acute effect of intraperitoneally administered prolactin (0.2, 0.4, and 0.6
      mg/kg body weight) on passive calcium transport in duodenum, proximal jejunum,
      and ileum of sexually mature female Wistar rats was investigated by using an in
      vivo perfusion technique. Test solution containing (in mM) NaCl, 100; KCl, 4.7;
      MgSO4, 1.2; CaCl2, 20; D-glucose, 11; sodium ferrocyanide (Na4Fe(CN)6), an index
      of net water transport, 20; and 0.7 microCi 45CaCl2 (1 Ci = 37 GBq) was perfused
      through the 10-cm intestinal loop for 60 min. Results showed that 0.4 mg
      prolactin/kg body weight significantly increased duodenal net Ca absorption (net
      Ca) from 23.81 +/- 1.84 to 30.56 +/- 1.57 mmol/g dry weight (p < 0.05) by
      stimulating the lumen to plasma calcium flux (CaL-P). The jejunum responded to
      0.2, 0.4, and 0.6 mg prolactin/kg body weight by reversing from net Ca absorption
      of 18.60 +/- 1.70 mmol/g dry weight to net secretion of -3.30 +/- 1.56, -10.39 +/
      2.21, and -11.79 +/- 2.04 mmol/g dry weight (p < 0.01), respectively, as a
      result of a dose-dependent increase in plasma to lumen calcium flux (CaP-L).
      Calcium fluxes in the ileum on the other hand did not respond to prolactin. There
      was a close correlation between net water flux and net calcium flux in all three
      intestinal segments under basal condition regardless of the luminal sodium
      concentration. However, this correlation was lost after prolactin administration,
      which while having no effect on net water flux, altered the duodenal and jejunal
      calcium fluxes. By varying the luminal concentration of sodium, it was found that
      the stimulatory effect of 0.4 mg prolactin/kg body weight on the duodenal CaL-P
      was reduced when compared with control, i.e., 17.84 +/- 0.91 vs. 26.64 +/- 1.05
      mmol/g dry weight at a sodium concentration of 180 mM, and 14.48 +/- 0.99 vs.
      20.12 +/- 1.34 mmol/g dry weight at a sodium concentration of 140 mM. At a sodium
      concentration of 80 mM, the prolactin effect was absent. Since duodenal Na(+)-K+
      ATPase activity was increased by prolactin from 3.77 +/- 0.16 to 4.95 +/- 0.30
      mumol Pi.mg-1 protein.h-1 (p < 0.05), sodium dependency of the prolactin-enhanced
      lumen to plasma calcium flux may be related to both sodium-induced water flow and
      calcium-sodium exchange across the basolateral membrane. Thus, it was postulated
      that under basal condition, net calcium transport in the small intestine occurred
      with the sodium-induced water transport along the paracellular pathway. However,
      after prolactin administration, this association was lost. Prolactin-enhanced
      lumen to plasma calcium flux in the duodenum was sodium dependent and involved
      the Na(+)-K+ ATPase activity. In the proximal jejunum, prolactin stimulated
      plasma to lumen calcium flux, but the mechanism was not known.

PMID- 9635156
TI  - Muscarinic inhibition of substance P induced ion secretion in piglet jejunum.
AB  - We examined the effects of the muscarinic agonist carbachol on ion secretion
      induced by substance P (SP) in piglet jejunal tissues mounted in Ussing chambers.
      Tetrodotoxin was present in all solutions to inhibit neural activity. Carbachol
      added 10 min prior to 0.75 microM SP dose dependently inhibited subsequent SP
      responses, with 90% inhibition at 10 microM carbachol. Addition of an equipotent
      dose of SP (7.5 microM) had no effect on subsequent carbachol-induced secretion.
      Carbachol's inhibition of SP-induced secretion was evident for at least 45 min
      and was abolished by prior addition of the M3 receptor antagonist 4
      diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP), but remained intact in
      the presence of the M2 antagonist gallamine or the nicotinic antagonist
      mecamylamine. Atropine added 10 min after carbachol restored subsequent SP
      responses toward control levels. Carbachol also reduced secretory responses to
      histamine and, to a lesser extent, prostaglandin E2 (PGE2). SP-induced secretion
      was not affected by prior addition of histamine and was reduced by PGE2 only at
      the highest PGE2 concentration. The results suggest that activation of the
      epithelial M3 receptor by carbachol inhibits subsequent secretory responses to
      the calcium-mediated agonists SP and histamine in piglet jejunum. This may
      reflect muscarinic activation of a negative messenger in epithelial cells that
      limits Cl- secretion.

PMID- 9635157
TI  - Antigen-induced responses in lung parenchymal strips during sinusoidal
      oscillation.
AB  - We have recently demonstrated that tissue resistance increases during the early
      response to antigen challenge in sensitized Brown-Norway rats. The purpose of the
      present study was to investigate in vitro the dynamic tissue response to antigen
      challenge and the involvement of the mediators, i.e., serotonin (5HT) and
      leukotriene D4 (LTD4). In addition, we questioned whether strips from sensitized
      rats responded differently to nonspecific challenge compared with those of
      unsensitized controls. We sensitized Brown-Norway rats with ovalbumin and
      performed experiments using strips of subpleural parenchyma. Tissue strips were
      challenged with ovalbumin in the bath; in some experiments the tissues were
      exposed to methysergide (10(-6) M), a 5HT antagonist, or MK-571 (10(-6) M), a
      LTD4 receptor antagonist, or both, prior to challenge. At the end of the
      experiment all tissues were exposed to carbacholine (10(-3) M). Oscillation
      mechanics of tissue strips were studied and values of resistance (R), elastance
      (E), and hysteresivity (eta) were obtained. During ovalbumin challenge in
      sensitized tissues, R, E, and eta increased significantly (% change in R, 12.1 +/
      2.1%; % change in E, 3.8 +/- 1.3%; % change in eta, 9.3 +/- 2.8%). Both
      methysergide and MK-571 reduced the increase in R (3.0 +/- 0.6 and 3.2 +/- 0.8%,
      respectively, p < 0.05 vs. ovalbumin). There was no difference between sensitized
      and unsensitized strips in the response to carbacholine challenge. These data
      suggest that the oscillatory behaviour of tissue strips from sensitized rats is
      altered after ovalbumin challenge. The mechanism of that response is mediated by
      both 5HT and LTD4.

PMID- 9635158
TI  - Effect of endothelium removal on prostaglandin and nitric oxide function in
      pulmonary resistance arteries in the lamb.
AB  - We have recently shown that isolated pulmonary resistance arteries of the fetal
      lamb have prostaglandin (PG) I2 based and nitric oxide (NO) based relaxing
      mechanisms, which are activated by oxygen (at neonatal levels) and bradykinin.
      The present study was carried out to ascertain whether these mechanisms remain
      operational after removal of the endothelium. Endothelium-denuded vessels pre
      equilibrated at a neonatal Po2 were not affected by indomethacin (2.8 microM),
      while they contracted weakly to NG-nitro-L-arginine methyl ester (L-NAME, 100
      microM). However, the latter response did not reach significance and resembled
      that of intact vessels at fetal Po2. Bradykinin (0.1-100 nM) dose dependently
      (from 1-3 nM upwards) relaxed endothelium-denuded arteries that had been
      precontracted with a thromboxane (TX) A2 analog (ONO-11113, 0.1 microM) or excess
      potassium (5 mM Ca2+ in K(+)-Krebs) at a neonatal Po2. The response was the same
      under the two conditions, but it was smaller than that of intact arteries.
      Bradykinin relaxation of ONO-11113-contracted arteries was completely or nearly
      completely inhibited by indomethacin and L-NAME. We conclude that endothelium
      denuded, pulmonary resistance arteries maintain PG (conceivably PGI2) mediated
      and NO-mediated relaxing mechanisms. These extra-endothelial mechanisms are
      activated by bradykinin but not by oxygen.

PMID- 9635159
TI  - Presence of NK1 receptors on a mucosal-like mast cell line, RBL-2H3 cells.
AB  - Reverse transcription--polymerase chain reaction of mRNA from rat RBL-2H3 cells
      yielded a 316 base pair band consistent with that predicted for the neurokinin-1
      (NK1) receptor. Saturation and competition binding with 125I-labeled Bolton
      Hunter substance P, substance P fragments, and a series of selective tachykinin
      receptor agonists and antagonists demonstrated that RBL-2H3 cells express high
      affinity binding sites for substance P on their surfaces with the kinetic and
      pharmacological properties of NK1 receptors. The pharmacology of these 125I
      labeled substance P binding sites was (from most to least potent)
      [Sar9,Met(O2)11]substance P > substance P 4-11 >> GR82334 << MEN 10,376. However,
      substance P 1-4, substance P 8-11, substance P 9-11, and [Trp7, beta
      Ala8]neurokinin A 4-10 failed to compete for binding. The metabolically stable
      NK1 receptor agonist, [Sar9,Met(O2)11] substance P, caused a 49% increase in 5
      hydroxytryptamine release above basal levels. The results demonstrate the
      presence of functional NK1 receptors on RBL-2H3 cells, a mucosal-like mast cell
      line.

PMID- 9635160
TI  - Electrical conduction within the cerebrovasculature of stroke-prone spontaneously
      hypertensive rats.
AB  - Alterations in electrical conductivity between smooth muscle cells (SMCs) can
      alter the spread and effectiveness of electromechanical SMC contraction. We
      attempted to determine whether alterations in pressure-dependent constriction
      (PDC) occurring in relation to stroke development within the middle cerebral
      arteries (MCAs) of Wistar-Kyoto stroke-prone hypertensive rats (SHRsp) were
      associated with changes in electrical conductivity between the SMCs. Current was
      injected into nonpressurized MCAs, using a suction electrode. The conducting
      distance along the length of the MCA where the amplitude of the membrane
      potential deflection (electronic potential) produced by current injection
      declined to 1/e (length constant) was used to measure conductivity. PDC to a 100
      mmHg pressure step was measured with a pressure myograph. A loss of PDC in the
      MCAs of SHRsp preceded stroke development. Heptanol (4 mM), a gap junction
      communication inhibitor, reversibly inhibited conductivity and PDC in the MCA of
      prestroke SHRsp. The ability of heptanol to reversibly inhibit PDC was likely not
      related to it's ability to alter electrical conduction. The length constant of
      electrical conduction in the MCAs was about 0.75 mm and didn't differ between MCA
      sampled from pre-versus post-stroke SHRsp or Sprague-Dawley rats. It was
      concluded that alterations in electrical conductivity along the MCA could modify
      the spread of PDC, but such changes do not contribute to the loss of PDC within
      the MCA of poststroke SHRsp.

PMID- 9635161
TI  - Plasma and lipoprotein lipid composition and hepatic antioxidant status in
      spontaneously hypertensive (SHR) and normotensive (WKY) rats.
AB  - Plasma and lipoprotein lipid composition and endogenous hepatic antioxidant
      status were investigated in hypertensive, 14-week-old spontaneously hypertensive
      (SHR) and normotensive Wistar-Kyoto (WKY) rats fed a standard commercial rat
      chow. Total plasma calcium and magnesium concentrations were similar between both
      rat strains; however, systolic blood pressure in SHR was greater than in WKY at
      13 weeks of age (197 +/- 12 vs. 132 +/- 14 mmHg; p < or = 0.05), confirming
      hypertension in SHR. Total plasma cholesterol and triacylglycerol concentrations
      were lower (p < or = 0.05) in SHR compared with WKY. A lower (p < 0.05) HDL
      cholesterol level in SHR plasma resulted in a higher LDL to HDL cholesterol ratio
      compared with WKY counterparts. No significant differences in the relative
      proportion of HDL apolipoprotein A-I fraction were observed between SHR and WKY.
      Both SHR VLDL and HDL triacylglycerol fractions were lower (p < 0.05) in SHR than
      WKY. Analysis of liver antioxidant enzyme activities showed no differences in rat
      liver superoxide dismutase (SOD), but lower (p < 0.05) liver glutathione
      peroxidase (GSH-Px) activity in SHR. However, liver glutathione (GSH) levels were
      similar in SHR and WKY counterparts. A possible compensatory effect to the
      oxidative status of SHR was suggested by the significant (p < 0.05) increase in
      both liver catalase (CAT) and glutathione reductase (GSSG-Red) activities.
      Despite these results, in vitro oxidative challenge studies with H2O2
      demonstrated a greater susceptibility of liver to GSH depletion in the SHR,
      although no parallel change in thiobarbituric acid reactive substances (TBARS)
      production was observed. The comparatively lower plasma cholesterol observed in
      hypertensive SHR paralleled specific differences in liver catalase and
      glutathione redox antioxidant enzyme activities.

PMID- 9635162
TI  - Effects of a selective phosphodiesterase IV inhibitor (CDP-840) in a leukotriene
      dependent non-human primate model of allergic asthma.
AB  - The activity of CDP-840, a novel, selective phosphodiesterase IV inhibitor was
      determined in a leukotriene-dependent non-human primate model of allergic asthma.
      Measurements of specific airway resistance (sRaw) were recorded in a dual chamber
      plethysmograph for 1 h and 3-5 h after challenge of allergic conscious squirrel
      monkeys with an aerosol of ascaris antigen. Orally administered CDP-840 (10
      mg/kg; 1 h before challenge) produced partial inhibition (41 and 45%,
      respectively) of both the acute (1 h post antigen) response and the late (3-5 h
      post antigen) response to antigen but failed to alter the response to an aerosol
      of leukotriene D4. In a second series of experiments, intravenous CDP-840 (5
      mg/kg; 30 min before challenge) showed improved potency, producing 82% inhibition
      of the early and 51% inhibition of the late phase response. CDP-840 was inactive
      when tested intravenously at 1 mg/kg and was inactive against the 3-5 h response
      when administered after the early phase response (5 mg/kg; i.v. 60 min post
      antigen challenge). The novel phosphodiesterase IV inhibitor CDP-840 selectively
      inhibited antigen-induced bronchoconstriction in conscious squirrel monkeys. This
      effect appears to be independent of any direct bronchodilator action. It is
      concluded that the activity of CDP-840 in this model may be due to an inhibitory
      effect on mediator (e.g., leukotriene) release.

PMID- 9635163
TI  - The study of a physiological significance of prolactin in the regulation of
      calcium metabolism during pregnancy and lactation in rats.
AB  - Since a pharmacological dose of prolactin has previously been reported to enhance
      calcium absorption and bone calcium turnover, the role of endogenous prolactin in
      the regulation of calcium metabolism was investigated in the balance studies of
      Wistar rats between days 17 and 20 of first (P1) and fourth (P4) pregnancy and
      between days 12 and 15 of lactation (L). Each group was divided into 3 subgroups:
      one subgroup was given 0.9% NaCl (control); one was given 0.3 mg
      bromocriptine/100 g body weight ip twice daily for 3 days (to suppress prolactin
      secretion); and one was given bromocriptine and 0.25 mg prolactin/100 g body
      weight sc daily for 3 days. All three groups received 1 mL/100 g body weight of
      1.25 mM calcium gluconate containing 2 mCi (1 Ci = 37 GBq) 45Ca daily for 3 days.
      Compared with the two pregnant controls, the L group had higher food consumption
      and higher fecal calcium excretion and lower urinary calcium excretion (%
      intake). Bromocriptine administration increased total calcium excretion from 59%
      intake to 84 and 66% intake in P1 and P4, respectively, suggesting that
      endogenous prolactin decreased total calcium excretion. On the other hand,
      exogenous prolactin had no effect on the calcium balance of P1 but increased the
      total calcium excretion in P4 from 57 to 66% intake. In contrast, the calcium
      balance of lactating rats was not altered by suppression of endogenous prolactin
      secretion or exogenous prolactin. Considering bone 45Ca content as representing
      bone Ca turnover, a lower value of bone 45Ca content indicated an accelerated
      bone Ca turnover. It was found that bromocriptine had no effect in P1 but
      decreased bone Ca turnover rate in the P4 and L groups, indicating an
      accelerating effect of endogenous prolactin on bone Ca turnover in the P4 and L
      groups. Exogenous prolactin, on the other hand, decreased bone Ca turnover rate
      in every group. Muscle Ca turnover was affected by bromocriptine and exogenous
      prolactin in the same manner as bone 45Ca contents. Interestingly, the biphasic
      action of prolactin was demonstrated in both calcium absorption and bone calcium
      turnover. It could be concluded that during pregnancy and lactation, endogenous
      prolactin increases food consumption, fractional calcium absorption, and bone
      calcium turnover, apparently to increase calcium availability for fetal
      development and milk calcium secretion.

PMID- 9635164
TI  - Heparin-releasable lipoprotein lipase activity is increased in cardiomyocytes
      after culture.
AB  - The activity of lipoprotein lipase (LPL) in adult rat heart cardiomyocytes after
      overnight culture on laminin-coated plates for 18-22 h was compared with enzyme
      activity in freshly isolated cardiomyocytes. LPL activity in cellular homogenates
      from cultured cardiomyocytes and freshly isolated cells was 240 and 233 nmol
      oleate released h-1.mg-1 protein, respectively. LPL specific activity (mU/ng LPL
      protein) was 0.07 in cultured cells compared with 0.42 in freshly isolated cells,
      indicating an increased content of inactive LPL mass after overnight culture. The
      heparin-induced release of LPL activity into the medium of cultured
      cardiomyocytes (198 nmol.h-1.mg-1) was much greater than heparin-releasable LPL
      (HR-LPL) activity (59 nmol.h-1.mg-1) from freshly isolated cells. HR-LPL activity
      from cultured cardiomyocytes was dependent on serum (16.3-fold activation) and
      was inhibited by high ionic strength (1 M NaCl) and by a polyclonal antibody to
      LPL. Cultured cardiomyocytes also had more immunodetectable LPL on the cell
      surface compared with freshly isolated cardiomyocytes, consistent with increased
      HR-LPL activity. Therefore, overnight culture may permit cardiomyocytes time to
      recover from the stress of isolation by increasing the content of LPL on the cell
      surface.

PMID- 9635165
TI  - Serum leptin levels and energy expenditure in normal weight women.
AB  - To investigate whether circulating leptin levels are associated with energy
      expenditure in healthy humans, doubly labeled water energy measurements and food
      intake assessment were carried out in 27 women (mean age, 48.6 years; weight,
      61.9 kg; body mass index, 23.2). Energy expenditure was determined over 13 days.
      Food intake was measured by 7-day food records. Leptin was measured by
      radioimmunoassay. Leptin level was strongly associated with percentage body fat
      (r = 0.59; p < 0.001), fat mass (r = 0.60; p < 0.001), and body mass index (r =
      0.41; p = 0.03), but no correlation was observed with energy expenditure (r =
      0.02; p = 0.93). After controlling for percentage body fat, a positive
      association of leptin level with energy expenditure of marginal significance (p =
      0.06) was observed. There were no significant univariate associations of age,
      physical activity, lean body mass, height, or dietary variables with leptin
      level. When controlling for body fat, a significant positive correlation was
      observed for percent energy from carbohydrate and negative correlations with
      dietary fat and alcohol intake. These findings confirm previous associations
      between leptin and body fat content and suggest a relationship between serum
      leptin and energy expenditure level in healthy humans.

PMID- 9635166
TI  - Microbial resistance to antimicrobial drugs.

PMID- 9635167
TI  - Questioning some of the CVMA pet food recommendations.

PMID- 9635168
TI  - ELISA testing for antibody to Mycobacterium paratuberculosis.

PMID- 9635169
TI  - An ethicist's commentary on the case of the cat who fractures both legs after a
      declaw.

PMID- 9635170
TI  - End tidal halothane concentration and postoperative analgesia requirements in
      dogs: a comparison between intravenous oxymorphone and epidural bupivacaine alone
      and in combination with oxymorphone.
AB  - The purpose of this study was to compare the effects of epidural bupivacaine
      (BUP) and oxymorphone/bupivacaine (O/B) and intravenous (i.v.) oxymorphone (IVO)
      on halothane requirements during hind end surgery and postoperative analgesia in
      24 dogs. Dogs were randomly assigned to treatment groups: O/B--oxymorphone (0.1
      mg/kg) in 0.75% bupivacaine (1 mg/kg for a total volume of 0.2 ml/kg); BUP--0.5%
      bupivacaine (1 mg/kg for a total volume of 0.2 ml/kg) with i.v. oxymorphone (0.05
      mg/kg) postoperatively; and IVO--oxymorphone (0.05 mg/kg) pre- and
      postoperatively. Heart rate (HR), respiratory rate, arterial blood pressure, end
      tidal carbon dioxide and halothane, and arterial blood gases were recorded prior
      to treatment and every 15 minutes thereafter. Once surgery had begun, end-tidal
      halothane concentrations were decreased as low as possible while still
      maintaining a stable anesthetic plane. Data were analyzed using ANOVA with P <
      0.05 considered significant. End-tidal halothane requirements did not differ
      significantly among treatments. Respiratory depression was increased and HR was
      decreased in the O/B and IVO groups. Postoperative analgesic requirements were
      significantly less in dogs receiving O/B.

PMID- 9635171
TI  - External skeletal fixation for treatment of comminuted fractures in wapiti: 5
      cases.
AB  - External skeletal fixators were used successfully to treat severely comminuted
      fractures in 5 wapiti.

PMID- 9635172
TI  - Cholecystadenocarcinoma in a cat.
AB  - A malignant neoplastic process originating from gall bladder epithelium was
      diagnosed in a 14-year-old, spayed female, domestic shorthair cat. The tumor
      produced widespread pulmonary and lymphatic metastases. The clinical and
      pathological manifestations are described. Neoplasia arising from the gall
      bladder epithelium is rarely reported in animals.

PMID- 9635173
TI  - Intestinal obstruction by stones in a turtle.

PMID- 9635174
TI  - Streptococcus acidominimus in a case of bovine fibrinopurulent metritis.

PMID- 9635175
TI  - Bacterial resistance.

PMID- 9635177
TI  - A clear view.

PMID- 9635178
TI  - Illusions as neuro-signs.

PMID- 9635179
TI  - A bacterial antibiotic resistance gene with eukaryotic origins.

PMID- 9635180
TI  - Nucleocytoplasmic transport: driving and directing transport.
AB  - Nucleocytoplasmic transport involves assembly and movement across the nuclear
      envelope of cargo-receptor complexes that interact with the small GTPase Ran. The
      asymmetric distribution of Ran regulator proteins, RanGAP1 and RCC1, provides the
      driving force and directionality for nuclear transport.

PMID- 9635181
TI  - Chromatin transcription: clearing the gridlock.
AB  - A factor has been purified that specifically facilitates RNA chain elongation in
      a chromatin context; the properties of this factor help to define the challenges
      that lie ahead in understanding how RNA polymerase manages to transcribe DNA that
      is packaged into chromatin.

PMID- 9635182
TI  - Neurophysiology: sensing and categorizing.
AB  - Objects differ along many stimulus dimensions, but observers typically group them
      into fewer 'categories' according to their potential use or behavioral relevance.
      New experiments in awake, behaving monkeys open a window onto the process of
      stimulus categorization within the central nervous system.

PMID- 9635183
TI  - Biodiversity conservation: does phylogeny matter?
AB  - To conserve biodiversity, it is necessary not only to maximize the number of taxa
      that are saved today, but also to guarantee the maintenance of high levels of
      biological diversity in the future. A recent analysis argues that, to achieve
      this, consideration of phylogeny is essential.

PMID- 9635184
TI  - Chromosome movement: kinetochores motor along.
AB  - The equal division of chromosomes among daughter cells at mitosis involves a
      complex series of kinetochore-dependent chromosome movements. The kinetochore
      associated CENP-E motor protein is critical for the sustained movement of
      chromosomes towards the metaphase plate during chromosome congression.

PMID- 9635185
TI  - Integrins: a role for adhesion molecules in olfactory memory.
AB  - A gene required for short-term memory in Drosophila, Volado, encodes an alpha
      integrin and is preferentially expressed in the mushroom bodies of the adult
      brain. Adhesion molecules of this kind may play a role in olfactory memory by
      altering the strength of synaptic connections in an experience-dependent manner.

PMID- 9635186
TI  - Membrane fusion: all done with SNAREpins?
AB  - SNARE proteins are sufficient to fuse artificial membranes together. In the cell,
      vesicle transport may rely on fusion mediated by interaction between vesicle (v)
      and target (t) SNAREs, whereas the homotypic fusion of organelle biogenesis may
      be mediated by t-SNARE-t-SNARE interaction.

PMID- 9635187
TI  - Intracellular motility: how can we all work together?
AB  - Recent results reinforce the view that actin-based and microtubule-based motility
      systems do not operate independently, but are used in coordinated fashion to
      determine intracellular localization of cargo such as organelles.

PMID- 9635188
TI  - Rng2p, a protein required for cytokinesis in fission yeast, is a component of the
      actomyosin ring and the spindle pole body.
AB  - BACKGROUND: An actomyosin-based contractile ring plays a pivotal role in
      cytokinesis. Despite the identification of many components of the ring, the steps
      involved in its assembly are unknown. The fission yeast Schizosaccharomyces pombe
      is an attractive organism in which to study cytokinesis because its cell cycle
      has been well characterized; it divides by medial fission using an actomyosin
      ring; and a number of S. pombe mutants defective in actomyosin ring assembly have
      been isolated. Here, we have characterized one such mutant, rng2. RESULTS:
      Temperature-sensitive rng2 mutants accumulated F-actin cables in the medial
      region of the cell but failed to organize the cables into a ring. In rng2-null
      mutants, only a spot-like structure containing F-actin was detected. The rng2+
      gene encodes a protein related to human IQGAP1, a protein that binds actin and
      calmodulin and is a potential effector for the Rho family of GTPases. Rng2p
      localized to the actomyosin ring and to the spindle pole body (SPB) of interphase
      and mitotic cells. Localization of Rng2p to the actomyosin ring but not the SPB
      required F-actin. Rng2p interacted with calmodulin, a component of the SPB and
      the actomyosin ring. The rng2 gene showed genetic interactions with three other
      actomyosin ring assembly mutants, cdc4, cdc12, and rng5. CONCLUSIONS: The S.
      pombe IQGAP-related protein Rng2p is a component of the actomyosin ring and the
      SPB and is required for actomyosin ring construction following assembly of F
      actin at the division site.

PMID- 9635189
TI  - Roles of Armadillo, a Drosophila catenin, during central nervous system
      development.
AB  - BACKGROUND: Neural development requires that neurons communicate and co-operate
      with one another and with other cell types in their environment. Drosophila
      Armadillo and its vertebrate homolog beta-catenin have dual roles in epithelial
      cells: transducing signals from the Wingless/Wnt family of proteins and working
      with cadherins to mediate cell adhesion. Wingless/Wnt signaling also directs
      certain cell fates in the central nervous system (CNS), and cadherins and
      catenins are thought to function together during neural development. RESULTS: We
      identified and analyzed the biochemical properties of a second armadillo isoform,
      with a truncated carboxyl terminus generated by alternative splicing. This
      isoform was found to accumulate in differentiating neurons. Using armadillo
      alleles that selectively inactivate the cell adhesion or the Wingless signaling
      functions of Armadillo, we found that Armadillo had two sequential roles in
      neural development. Armadillo function in Wingless signal transduction was
      required early in development for determination of neuroblast fate. Later in
      development, disruption of the cell-cell adhesion function of Armadillo resulted
      in subtle defects in the construction of the axonal scaffold. Mutations in the
      gene encoding the Drosophila tyrosine kinase Abelson substantially enhanced the
      severity of the CNS phenotype of armadillo mutations, consistent with these
      proteins functioning co-operatively at adherens junctions in both the CNS and the
      epidermis. CONCLUSIONS: This is one of the first demonstrations of a role for the
      cadherin-catenin system in the normal development of the CNS. The genetic
      interactions between armadillo and abelson point to a possible role for the
      tyrosine kinase Abelson in cell-cell adhesive junctions in both the CNS and the
      epidermis.

PMID- 9635190
TI  - Cut1 is loaded onto the spindle by binding to Cut2 and promotes anaphase spindle
      movement upon Cut2 proteolysis.
AB  - BACKGROUND: The Cut1 and Cut2 proteins of the fission yeast Schizosaccharomyces
      pombe form a complex and are required for the separation of sister chromatids
      during anaphase. Polyubiquitinated Cut2 degrades at the onset of anaphase and
      this degradation, like that of mitotic cyclin, is dependent on the anaphase
      promoting complex/cyclosome. Expression of Cut2 that cannot be degraded blocks
      sister chromatid separation and anaphase spindle elongation. Here, we have
      investigated the role of the Cut1-Cut2 interaction in sister chromatid
      separation. RESULTS: The carboxyl terminus of Cut2 interacts with the amino
      terminus of Cut1, and temperature-sensitive Cut2 mutants expressed Cut2 proteins
      that contain substitutions in the carboxyl terminus and fail to interact with
      Cut1, resulting in aberrant anaphase. Localization of Cut1 alters dramatically
      during the cell cycle. Cut1 is retained in the cytoplasm during interphase and
      moves to the mitotic spindle pole bodies and the spindle upon entry into
      prophase, when spindles are formed. The association between Cut2 and Cut1 is
      needed for the localization of Cut1 to the spindles, as Cut1 remains unbound to
      the spindle if complex formation is impaired. Cut2 degrades during anaphase, but
      Cut1 remains bound to the anaphase spindle. This association with the anaphase
      spindle requires the conserved carboxyl terminus of Cut1. CONCLUSIONS: Complex
      formation between Cut1 and Cut2 is needed for the onset of normal anaphase. Cut2
      is required for loading Cut1 onto the spindle at prophase and Cut2 proteolysis is
      needed for the active participation of Cut1 in sister chromatid separation.

PMID- 9635191
TI  - The importance of timing differentiation during limb muscle development.
AB  - BACKGROUND: Skeletal muscle of trunk, limbs and tongue develops from a small
      population of cells that originates from somites. Although promoters and
      inhibitors of muscle differentiation have been isolated, nothing is known about
      how the amplification of the muscle precursor pool is regulated; this
      amplification provides muscle mass during development. Furthermore, little is
      known about how cells accumulate in the pre-muscle masses in the limbs. We
      investigated the role of bone morphogenetic protein (BMPs) and Sonic hedgehog
      (Shh) during proliferation, differentiation and positioning of muscle. RESULTS:
      The proliferation of muscle precursors in limbs was linked to Pax-3 expression.
      Ectoderm removal downregulated Pax-3 expression, arrested proliferation and
      prematurely initiated muscle differentiation which exhausted the muscle precursor
      pool and prevented further muscle growth. BMP-2, BMP-4 and BMP-7 had a dose
      dependent effect on pre-myogenic cells: low concentrations maintained a Pax-3
      expressing proliferative population, substituting for ectoderm-derived
      proliferative signals and delaying differentiation, whereas high concentrations
      prevented muscle development, probably by inducing apoptosis. In the limb, Shh
      upregulated Bmp-2 and Bmp-7 expression which delayed muscle differentiation,
      upregulated Pax-3, amplified the muscle precursor population and stimulated
      excessive muscle growth. CONCLUSIONS: These data indicate that embryonic muscle
      growth requires muscle differentiation to be delayed. Muscle differentiation may
      occur through a default pathway after cells escape proliferative signals.
      Positioning of muscle is regulated by high concentrations of BMPs, thus a single
      type of signalling molecule can determine crucial steps in muscle development:
      when and where to proliferate, and when and where to differentiate.

PMID- 9635192
TI  - Mutation of yeast Ku genes disrupts the subnuclear organization of telomeres.
AB  - The mammalian Ku70 and Ku86 proteins form a heterodimer that binds to the ends of
      double-stranded DNA in vitro and is required for repair of radiation-induced
      strand breaks and V(D)J recombination [1,2]. Deletion of the Saccharomyces
      cerevisiae genes HDF1 and HDF2--encoding yKu70p and yKu80p, respectively-
      enhances radiation sensitivity in a rad52 background [3,4]. In addition to repair
      defects, the length of the TG-rich repeat on yeast telomere ends shortens
      dramatically [5,6]. We have shown previously that in yeast interphase nuclei,
      telomeres are clustered in a limited number of foci near the nuclear periphery
      [7], but the elements that mediate this localization remained unknown. We report
      here that deletion of the genes encoding yKu70p or its partner yKu80p altered the
      positioning of telomeric DNA in the yeast nucleus. These are the first mutants
      shown to affect the subnuclear localization of telomeres. Strains deficient for
      either yKu70p or yKu80p lost telomeric silencing, although they maintained
      repression at the silent mating-type loci. In addition, the telomere-associated
      silencing factors Sir3p and Sir4p and the TG-repeat-binding protein Rap1p lost
      their punctate pattern of staining and became dispersed throughout the
      nucleoplasm. Our results implicate the yeast Ku proteins directly in aspects of
      telomere organization, which in turn affects the repression of telomere-proximal
      genes.

PMID- 9635193
TI  - Telomere maintenance is dependent on activities required for end repair of double
      strand breaks.
AB  - Telomeres are functionally distinct from ends generated by chromosome breakage,
      in that telomeres, unlike double-strand breaks, are insulated from recombination
      with other chromosomal termini [1]. We report that the Ku heterodimer and the
      Rad50/Mre11/Xrs2 complex, both of which are required for repair of double-strand
      breaks [2-5], have separate roles in normal telomere maintenance in yeast. Using
      epistasis analysis, we show that the Ku end-binding complex defined a third
      telomere-associated activity, required in parallel with telomerase [6] and Cdc13,
      a protein binding the single-strand portion of telomere DNA [7,8]. Furthermore,
      loss of Ku function altered the expression of telomere-located genes, indicative
      of a disruption of telomeric chromatin. These data suggest that the Ku complex
      and the Cdc13 protein function as terminus-binding factors, contributing distinct
      roles in chromosome end protection. In contrast, MRE11 and RAD50 were required
      for the telomerase-mediated pathway, rather than for telomeric end protection; we
      propose that this complex functions to prepare DNA ends for telomerase to
      replicate. These results suggest that as a part of normal telomere maintenance,
      telomeres are identified as double-strand breaks, with additional mechanisms
      required to prevent telomere recombination. Ku, Cdc13 and telomerase define three
      epistasis groups required in parallel for telomere maintenance.

PMID- 9635194
TI  - Dissecting the role of N-myc in development using a single targeting vector to
      generate a series of alleles.
AB  - The N-myc proto-oncogene is expressed in many organs of the mouse embryo,
      suggesting that it has multiple functions. A null mutation leads to mid-gestation
      lethality [1-4], obscuring the later roles of the gene in organogenesis. We have
      generated a multi-purpose gene alteration by combining the potential for
      homologous and site-specific recombination in a single targeting vector, and
      using the selectable marker for neomycin-resistance, neo, to downregulate gene
      activity. This allowed us to create a series of alleles that led to different
      levels of N-myc expression. The phenotypes revealed a spectrum of developmental
      problems. The hypomorphic allele produced can be repaired in situ by Cre
      recombinase-mediated DNA excision. We show here for the first time the use of a
      single targeting vector to generate an allelic series. This, and the possibility
      of subsequent lineage-specific or conditional allele repair in situ, represent
      new genome modification strategies that can be used to investigate multiple
      functions of a single gene.

PMID- 9635195
TI  - Fate mapping of the mouse midbrain-hindbrain constriction using a site-specific
      recombination system.
AB  - The mouse midbrain-hindbrain constriction is centrally involved in patterning of
      the midbrain and anterior hindbrain (cerebellum), as revealed by recent genetic
      studies using mice and embryological studies in chick (reviewed in [1,2]). This
      region can act as an organizer region to induce midbrain and cerebellar
      development. Genes such as Engrailed-1, Pax-2 and Pax-5, which are expressed in
      the embryonic cells that will form the midbrain and the cerebellum, are required
      for development of these regions. Fate-mapping experiments at early somite stages
      in chick have revealed that the cerebellar primordium is located both anterior
      and posterior to the midbrain-hindbrain constriction, whereas midbrain precursors
      lie more anteriorly. Fate mapping in mice has been complicated by the
      inaccessibility of the postimplantation embryo. Here, we report the use of a new
      in vivo approach involving the Cre-IoxP site-specific recombination system [3] to
      map the fate of cells in the mouse midbrain-hindbrain constriction. We show that
      cells originating in the mouse dorsal midbrain-hindbrain constriction during
      embryonic days 9-12 contribute significantly to the medial cerebellum and
      colliculi. Our data demonstrate the feasibility of using a recombinase-based
      lineage-tracing system for fate mapping in the mouse.

PMID- 9635196
TI  - Differences between IL-4R alpha-deficient and IL-4-deficient mice reveal a role
      for IL-13 in the regulation of Th2 responses.
AB  - Allergens and infections with parasitic helminths preferentially induced Th2
      immune responses associated with elevated levels of serum immunoglobulin E (IgE)
      and expansion of eosinophils and mast cells. Interleukin-4 (IL-4) is a key
      cytokine in the differentiation of naive CD4+ T cells into Th2 cells, which
      produce a panel of cytokines including IL-4, IL-5, IL-6, IL-9, IL-10, and IL-13
      [1] and have been shown to trigger recovery from gastrointestinal nematodes [2].
      Nonetheless, mice deficient for IL-4 have been shown to develop residual Th2
      responses [3-5] and can expel the nematode Nippostrongylus brasiliensis [6],
      suggesting that there is a functional equivalent of IL-4 in these processes. IL
      13 is a cytokine that shares some, but not all, biological activities with IL-4
      [7,8]. There is now compelling evidence that IL-4 and IL-13 share receptor
      components, including IL-4R alpha and IL-13R alpha 1 [9]. In order to dissect the
      roles of IL-4 and IL-13 in the regulation of Th2 cells and in the response to
      nematode infections, we looked for differences between mice deficient for either
      the IL-4 gene or the IL-4R alpha gene. Unlike IL-4, IL-4R alpha was required for
      control of N. brasiliensis, and Th2 development during infection--as
      characterized by cytokine production, GATA-3 and surface CD30 expression--was
      more severely affected in IL-4R alpha-/- mice than in IL-4-/- mice. Injection of
      recombinant IL-13 induced worm expulsion in otherwise incompetent RAG2-/- mice.
      Our results suggest that IL-13 regulates Th2 responses to nematode infection and
      requires IL-4R alpha.

PMID- 9635197
TI  - Two phases of Hox gene regulation during early Xenopus development.
AB  - We have shown previously that fibroblast growth factor (FGF) signalling in
      posterior regions of the Xenopus embryo is required for the development of the
      trunk and tail via a molecular pathway that includes the caudal-related gene
      Xcad3 and the posterior Hox genes [1]. These results have been contested by the
      work of Kroll and Amaya [2], which shows that Xenopus embryos transgenic for a
      dominant-negative form of the FGF receptor (FGF-RI) express posterior Hox genes
      normally, leading these authors to suggest that the FGFs are not required for
      anteroposterior (A-P) patterning of the dorsal axis. In order to investigate the
      apparent discrepancy between these studies, we have produced Xenopus embryos
      transgenic for two inhibitors of the FGF/Caudal pathway: a kinase-deficient
      dominant-negative FGF receptor (XFD) [3]; and a domain-swapped form of Xcad3
      (Xcad-EnR) in which the activation domain of Xcad3 is replaced by the repression
      domain of the Drosophila Engrailed protein. Both of these were introduced as
      fusions with the green fluorescent protein (GFP), which allows identification of
      non-mosaic transgenic embryos at early gastrula stages by simply looking for GFP
      fluorescence. Analysis of gene expression in embryos transgenic for these
      constructs indicated that the activation of posterior Hox genes during early
      neurula stages absolutely requires FGF signalling and transcriptional activation
      by Xcad3, while the maintenance of Hox gene expression in the trunk and tail
      during later development is independent of both FGF and Xcad.

PMID- 9635198
TI  - Cognitive neuroscience.

PMID- 9635199
TI  - Beyond images.

PMID- 9635200
TI  - Beyond the single study: function/location metanalysis in cognitive neuroimaging.
AB  - Cognitive neuroimaging maps the brain locations of mental operations. This
      process is iterative, as no single study can fully characterize a mental
      operation or its brain location. This iterative discovery process, in combination
      with the location-reporting standard (i.e. spatial coordinates) of the cognitive
      neuroimaging community, has engendered a new form of metanalysis. Response
      locations from multiple studies have been analyzed collectively so as to better
      describe the spatial distribution of brain activations, with promising results.
      New hypotheses regarding elementary mental operations and their respective brain
      locations are being generated and refined via metanalysis. These hypotheses are
      being tested and confirmed by subsequent, prospective experiments.
      Function/location metanalysis is an important new tool for hypothesis generation
      in cognitive neuroimaging. This form of metanalysis is fundamentally different
      from the effect-size metanalyses prevalent in other literatures, with unique
      advantages and challenges.

PMID- 9635201
TI  - Brain mapping in animals and humans.
AB  - Studies using functional magnetic resonance imaging (fMRI) to map cortical areas
      in humans have revealed many similarities with recent cortical mapping studies
      from nonhuman primates as well as some striking differences. Improved methods for
      analyzing, displaying and averaging fMRI data on an unfolded cortical surface
      atlas are poised to improve the integration of information across burgeoning
      numbers of imaging studies. By combining fMRI with electrical and passive
      magnetic imaging modalities, the millisecond-to-millisecond sequence of
      activation of different cortical regions elicited by an event can be imaged,
      provided the regions are sufficiently far apart.

PMID- 9635202
TI  - Spatial maps for the control of movement.
AB  - Neurons in the ventral premotor cortex of the monkey encode the locations of
      visual, tactile, auditory and remembered stimuli. Some of these neurons encode
      the locations of stimuli with respect to the arm, and may be useful for guiding
      movements of the arm. Others encode the locations of stimuli with respect to the
      head, and may be useful for guiding movements of the head. We suggest that a
      general principle of sensory-motor integration is that the space surrounding the
      body is represented in body-part-centered coordinates. That is, there are
      multiple coordinate systems used to guide movement, each one attached to a
      different part of the body. This and other recent evidence from both monkeys and
      humans suggest that the formation of spatial maps in the brain and the guidance
      of limb and body movements do not proceed in separate stages but are closely
      integrated in both the parietal and frontal lobes.

PMID- 9635203
TI  - Temporal dynamics of early perceptual processing.
AB  - Recordings of electrical and magnetic brain responses to sensory stimulation
      provide high-resolution measures of the time course of early perceptual
      processing. Spatio-temporal analyses of brain activity patterns during the first
      200 ms after stimulus presentation have characterized the timing of attentional
      selection processes and different stages of feature encoding and pattern
      analyses. Recent studies that incorporate blood flow neuroimaging techniques
      provide support for mechanisms of early selection of attended visual inputs in
      extrastriate cortical pathways. The spatial tuning properties of early auditory
      selection have also been delineated. Electrical and magnetic responses that index
      the encoding of higher-order pattern information have been identified in both
      visual and auditory modalities and localized to specific cortical areas.

PMID- 9635204
TI  - Neural correlates of visual and motor decision processes.
AB  - Recent research has clarified and revealed characteristics of perceptual and
      motor decision processes in the brain. A democracy of sensory neurons
      discriminate the properties of a stimulus, while competition contrasts the
      attributes of stimuli across the visual field to locate conspicuous stimuli.
      Salience and significance are weighed to select an object on which to focus
      attention and action. Experimentally combining neural and mental chronometry has
      determined the contribution of perceptual and motor processes to the duration and
      variability of behavioral reaction time. Whereas perceptual processing occupies a
      relatively constant amount of time for a given stimulus condition, the processes
      of mapping particular stimuli onto the appropriate behavior and preparing the
      motor response provide flexibility but introduce delay and variability in
      reaction time.

PMID- 9635205
TI  - Perceiving visually presented objects: recognition, awareness, and modularity.
AB  - Object perception may involve seeing, recognition, preparation of actions, and
      emotional responses--functions that human brain imaging and neuropsychology
      suggest are localized separately. Perhaps because of this specialization, object
      perception is remarkably rapid and efficient. Representations of componential
      structure and interpolation from view-dependent images both play a part in object
      recognition. Unattended objects may be implicitly registered, but recent
      experiments suggest that attention is required to bind features, to represent
      three-dimensional structure, and to mediate awareness.

PMID- 9635206
TI  - Properties and mechanisms of perceptual priming.
AB  - Recent evidence suggests that the behavioral phenomenon of perceptual priming and
      the physiological finding of decreased neural responses with item repetition have
      similar properties. Both the behavioral and neurophysiological effects show
      graded changes with multiple repetition, are resistant to manipulations of
      particular stimulus attributes (e.g. size and location), and occur independently
      of awareness. These and other recent findings (e.g. from functional brain imaging
      in humans) suggest that perceptual priming may be mediated by decreased neural
      responses associated with perceptual learning.

PMID- 9635207
TI  - Recent developments in working memory.
AB  - Research on the visual and verbal subsystems of working memory has shown vigorous
      development, with PET, fMRI and behavioral data all supporting separate systems,
      with further fractionation being likely. Analysis of executive processes is
      revealing a range of subprocesses, providing a very fruitful field for the
      interaction of cognitive psychology, neuropsychology and functional imaging.

PMID- 9635208
TI  - To dream or not to dream? Relevant data from new neuroimaging and
      electrophysiological studies.
AB  - The study of sleep and dreams has enjoyed a major breakthrough with recent
      findings from brain imaging studies in humans. Several independent groups have
      shown global deactivation of the brain during non rapid eye movement sleep and a
      regionally selective reactivation during rapid eye movement sleep. These results
      are complemented by new brain lesion and electrophysiological recording data to
      give a detailed picture of the brain dynamics of changes in conscious state.

PMID- 9635209
TI  - Crossmodal attention.
AB  - Most selective attention research has considered only a single sensory modality
      at a time, but in the real world, our attention must be coordinated crossmodally.
      Recent studies reveal extensive crossmodal links in attention across the various
      modalities (i.e. audition, vision, touch and proprioception). Attention typically
      shifts to a common location across the modalities, despite the vast differences
      in their initial coding of space. These spatial synergies in attention can be
      maintained even when receptors are realigned across the modalities by changes in
      posture. Some crossmodal integration can arise preattentively. The mechanisms
      underlying these crossmodal links can be examined in a convergent manner by
      integrating behavioural studies of normal subjects and brain-damaged patients
      with neuroimaging and neurophysiological studies.

PMID- 9635210
TI  - Neural organization and plasticity of language.
AB  - Powerful advances in neuroimaging techniques have added to and refined classical
      descriptions of the neurobiology of language in adults. Recent studies have
      employed these methodologies to study the nature and extent of plasticity of
      language-relevant aspects of cerebral organization in adults, in early and late
      bilinguals and in people who have acquired language through different modalities.
      Studies of children have documented dynamic shifts in cerebral organization over
      the course of language acquisition. Each of these different approaches has
      revealed constraints on the identity of the neural systems that mediate language;
      these studies have also described the marked and specific effects of language
      experience on the organization of these systems.

PMID- 9635211
TI  - Images of psychopathology.
AB  - Brain imaging continues to provide important data about brain structure,
      neurotransmitter function and the physiological basis of cognitive processes, as
      these relate to schizophrenia and mood disorders. A unifying theoretical
      perspective, however, that can clarify the precise nature of the biological basis
      of these diverse psychiatric conditions is lacking. It is becoming increasingly
      evident that a lesion model is inappropriate and that a more relevant
      characterisation will be found in terms of disorders of functional
      interconnections between brain regions.

PMID- 9635212
TI  - Cognitive neuroscience of attention deficit hyperactivity disorder and
      hyperkinetic disorder.
AB  - Currently, diagnoses of attention deficit hyperactivity disorder (ADHD) and
      hyperkinetic disorder (HKD) are made on the basis of phenomenology, but
      information is accumulating from the neurosciences about the biological bases of
      these disorders. Recent studies addressing the neuropsychology, neuroanatomy,
      neurochemistry, and molecular biology of ADHD/HKD document abnormalities in well
      defined neuroanatomical networks and neurochemical pathways. Magnetic resonance
      imaging (MRI) studies have shown that some regions of the frontal lobes (anterior
      superior and inferior) and basal ganglia (caudate nucleus and globus pallidus)
      are about 10% smaller in ADHD groups than in control groups of children, and
      molecular genetic studies have shown that diagnosis of ADHD is associated with
      polymorphisms in some dopamine genes (the dopamine D4 receptor gene and the
      dopamine transporter gene).

PMID- 9635213
TI  - Genetically modified mice and cognition.
AB  - Cognition in transgenic and knockout mice is preferentially assessed by spatial
      learning in the Morris water maze. Awareness is growing, however, that the
      putative cognitive deficits observed using such a paradigm may be biased by the
      genetic background and behavioral peculiarities of the specific animals used.
      Recent progress in cognitive research includes new behavioral tests and refined
      analysis of performance impairments. Advances in our understanding of memory and
      learning are being made possible through use of transgenic rescue of disrupted
      genes, inducible and reversible gene targeting in selected brain regions, and
      single-cell recordings of hippocampal place cells in mutant mice.

PMID- 9635214
TI  - Recovery of cognitive functions following nonprogressive brain injury.
AB  - It has recently become clear that the adult human brain is capable of more
      plasticity than previously thought. Investigations into the natural history of
      change following brain injury demonstrate that partial recovery of function can
      and does occur. Furthermore, there is increasing evidence that intervention
      through re-training or provision of compensatory memory aids can result in
      improved cognitive functioning.

PMID- 9635215
TI  - What is cognitive behavioural therapy and does it work?

PMID- 9635216
TI  - The hippocampus, consolidation and on-line memory.

PMID- 9635217
TI  - Consolidation and the hippocampal complex revisited: in defense of the multiple
      trace model.

PMID- 9635218
TI  - Contextualism and developmental psychopathology.

PMID- 9635219
TI  - Social context in developmental psychopathology: recommendations for future
      research from the MacArthur Network on Psychopathology and Development. The
      MacArthur Foundation Research Network on Psychopathology and Development.
AB  - Accumulating evidence suggests that social contexts in early life have important
      and complex effects on childhood psychopathology. Spurred by the lack of an
      explicit operational definition that could guide the study of such effects, we
      define a social context operationally as "a set of interpersonal conditions,
      relevant to a particular behavior or disorder and external to, but shaped and
      interpreted by, the individual child." Building on this definition, we offer a
      series of recommendations for future research, based on five theoretically
      derived propositions: (a) Contexts are nested and multidimensional; (b) contexts
      broaden, differentiate, and deepen with age, becoming more specific in their
      effects; (c) contexts and children are mutually determining; (d) a context's
      meaning to the child determines its effects on the child and arises from the
      context's ability to provide for fundamental needs; and (e) contexts should be
      selected for assessment in light of specific questions or outcomes. As reflected
      in an increasingly rich legacy of literature on child development and
      psychopathology, social contexts appear to influence emerging mental disorders
      through dynamic, bidirectional interactions with individual children. Future
      research will benefit from examining not only statistical interactions between
      child- and context-specific factors, but also the actual transactions between
      children and contexts and the transduction of contextual influences into pathways
      of biological mediation. Because adverse contexts exert powerful effects on the
      mental health of children, it is important for the field to generate new, more
      theoretically grounded research addressing the contextual determinants of
      psychological well-being and disorder.

PMID- 9635220
TI  - The effect of the level of aggression in the first grade classroom on the course
      and malleability of aggressive behavior into middle school.
AB  - This paper is on the influences of the classroom context on the course and
      malleability of aggressive behavior from entrance into first grade through the
      transition into middle school. Nineteen public elementary schools participated in
      developmental epidemiologically based preventive trials in first and second
      grades, one of which was directed at reducing aggressive, disruptive behavior. At
      the start of first grade, schools and teachers were randomly assigned to
      intervention or control conditions. Children within each school were assigned
      sequentially to classrooms from alphabetized lists, followed by checking to
      insure balanced assignment based on kindergarten behavior. Despite these
      procedures, by the end of first quarter, classrooms within schools differed
      markedly in levels of aggressive behavior. Children were followed through sixth
      grade, where their aggressive behavior was rated by middle school teachers.
      Strong interactive effects were found on the risk of being highly aggressive in
      middle school between the level of aggressive behavior in the first grade
      classrooms and each boy's own level of aggressive, disruptive behavior in first
      grade. The more aggressive first grade boys who were in higher aggressive first
      grade classrooms were at markedly increased risk, compared both to the median
      first grade boys, and compared to aggressive males in lower aggressive first
      grade classrooms. Boys were already behaving more aggressively than girls in
      first grade; and no similar classroom aggression effect was found among girls,
      although girls' own aggressive behavior did place them at increased risk. The
      preventive intervention effect, already reported elsewhere to reduce aggressive
      behavior among the more aggressive males, appeared to do so by reducing high
      levels of classroom aggression. First grade males' own poverty level was
      associated with higher risk of being more aggressive, disruptive in first grade,
      and thereby increased their vulnerability to classroom level of aggression. Both
      boys and girls in schools in poor communities were at increased risk of being
      highly aggressive in middle school regardless of their levels of aggressive
      behavior in first grade. These results are discussed in terms of life
      course/social field theory as applied to the role of contextual influences on the
      development and etiology of severe aggressive behavior.

PMID- 9635221
TI  - Resolving conflict creatively: evaluating the developmental effects of a school
      based violence prevention program in neighborhood and classroom context.
AB  - This study evaluated the short-term impact of a school-based violence prevention
      initiative on developmental processes thought to place children at risk for
      future aggression and violence and examined the influence of classroom and
      neighborhood contexts on the effectiveness of the violence prevention initiative.
      Two waves of developmental data (fall and spring) were analyzed from the 1st year
      of the evaluation of the Resolving Conflict Creatively Program (RCCP), which
      includes 5053 children from grades two to six from 11 elementary schools in New
      York City. Three distinct profiles of exposure to the intervention were derived
      from Management Information System (MIS) data on between classroom differences in
      teacher Training and Coaching in RCCP, Classroom Instruction in RCCP, and
      percentages of students who are Peer Mediators. Developmental processes that
      place children at risk were found to increase over the course of the school year.
      Children whose teachers had a moderate amount of training and coaching from RCCP
      and who taught many lessons showed significantly slower growth in aggression
      related processes, and less of a decrease in competence-related processes,
      compared to children whose teachers taught few or no lessons. Contrary to
      expectation, children whose teachers had a higher level of training and coaching
      in the RCCP but taught few lessons showed significantly faster growth over time
      in aggressive cognitions and behaviors. The impact of the intervention on
      children's social cognitions (but not on their interpersonal behaviors) varied by
      context. Specifically the positive effect of High Lessons was dampened for
      children in high-risk classrooms and neighborhoods. Implications for future
      research on developmental psychopathology in context and for the design of
      preventive interventions are discussed.

PMID- 9635222
TI  - Impoverishment and child maltreatment in African American and European American
      neighborhoods.
AB  - Although it is well documented that child maltreatment exerts a deleterious
      impact on child adaptation, much less is known about the precise etiological
      pathways that eventuate in child abuse and neglect. This paper reports on a
      multimethod ecological study of the relationship between neighborhood structural
      factors and child maltreatment reports in African American and European American
      census tracts. The study had two major components. First, in an aggregate
      analysis, the effects of four measures of community structure (impoverishment,
      child care burden, instability, and geographic isolation) on child maltreatment
      report rates were examined separately for predominantly African American (n = 94)
      and predominantly European American (n = 189) census tracts. Impoverishment in
      particular had a significantly weaker effect on maltreatment rates in African
      American than in European American neighborhoods. Second, focused ethnographies
      were conducted in four selected census tracts with child maltreatment report
      rates in the highest and lowest quartiles. Ethnographic data point to the
      importance of the social fabric in accounting for differences in child
      maltreatment report rates by predominant neighborhood ethnicity.

PMID- 9635223
TI  - An ecological-transactional analysis of children and contexts: the longitudinal
      interplay among child maltreatment, community violence, and children's
      symptomatology.
AB  - Cicchetti and Lynch have conceptualized ecological contexts as consisting of
      nested levels with varying degrees of proximity to the individual. These levels
      of the environment interact and transact with each other over time in shaping
      individual development and adaptation. With a sample of maltreated (n = 188) and
      nonmaltreated (n = 134) children between the ages of 7 and 12 years, this
      investigation employed a 1-year longitudinal design to conduct an ecological
      transactional analysis of the mutual relationships among community violence,
      child maltreatment, and children's functioning over time. Indicators of
      children's functioning were externalizing and internalizing behavior problems and
      self-rated traumatic stress reactions, depressive symptomatology, and self
      esteem. Either full or partial support was obtained for the study's primary
      hypotheses. Rates of maltreatment, particularly physical abuse, were related to
      levels of child-reported violence in the community. In addition, child
      maltreatment and exposure to community violence were related to different aspects
      of children's functioning. Specific effects were observed for neglect and sexual
      abuse and for witnessing and being victimized by violence in the community.
      Finally, there was evidence that children and their contexts mutually influence
      each other over time. Results were discussed within the framework of an
      ecological-transactional model of development.

PMID- 9635224
TI  - Structural and experiential neighborhood contexts, developmental stage, and
      antisocial behavior among urban adolescents in poverty.
AB  - This study explored the effects of structural and experiential neighborhood
      factors and developmental stage on antisocial behavior, among a sample of poor
      urban adolescents in New York City. Conceptually and empirically distinct
      profiles of neighborhood experience were derived from the data, based on measures
      of perceived neighborhood cohesion, poverty-related hassles, and involvement in
      neighborhood organizations and activities. Both the profiles of neighborhood
      experience and a measure of census-tract-level neighborhood hazard (poverty and
      violence) showed relationships to antisocial behavior. Contrary to expectation,
      higher levels of antisocial behavior were reported among adolescents residing in
      moderate-structural-risk neighborhoods than those in high-structural-risk
      neighborhoods. This effect held only for teens in middle (not early) adolescence
      and was stronger for teens perceiving their neighborhoods as hassling than for
      those who did not. Implications for future research and preventive intervention
      are discussed.

PMID- 9635225
TI  - Maternal depressive disorder and contextual risk: contributions to the
      development of attachment insecurity and behavior problems in toddlerhood.
AB  - Research has shown that offspring of depressed caregivers are at increased risk
      for maladaptive development and emotional difficulties. Specifically, infants and
      toddlers of depressed mothers have been shown to evidence higher percentages of
      insecure attachments and more behavioral difficulties than offspring of
      nondisordered mothers. However, even in studies that reveal significant
      differences between children of depressed and nondepressed caregivers, a
      substantial number of children with depressed caregivers do not evidence
      dysfunction. Such findings have resulted in increased attention to the broader
      social context in which children of depressed mothers develop. This investigation
      examined the direct influences of maternal depression on child development, as
      well as the role of contextual risks that may be particularly heightened in
      families with depressed parents. Toddlers with depressed mothers evidenced
      significantly more insecure attachments than did toddlers with nondisordered
      mothers, and this difference was not accounted for by contextual risk. In
      predicting child behavior problems, contextual risk was found to mediate the
      relation between maternal depression and child behavior problems. Father-report
      data on child behavior corroborated the mother report data. Results are discussed
      in terms of the diversity of functioning in offspring of depressed caregivers
      that can be attributed to varied levels of contextual risk accompanying
      depression.

PMID- 9635226
TI  - Mothering, fathering, and infant negativity as antecedents of boys' externalizing
      problems and inhibition at age 3 years: differential susceptibility to rearing
      experience?
AB  - To examine the effects of infant negative emotionality and of mothering and
      fathering during the toddler years on 3-year-old boys' externalizing problems and
      inhibition, as well as explore the proposition that children vary in their
      susceptibility to rearing influence, 125 first-born, Caucasian boys from
      maritally intact families were studied. Results revealed that when infant
      negativity is measured with objective, replicable, and discriminantly valid
      procedures, no relation obtains between it and externalizing problems (nor
      inhibition). Moreover, as hypothesized on the basis of prior work, parenting was
      a stronger predictor of externalizing problems and inhibition in the case of
      children who were highly negative as infants. Mothering proved a stronger
      predictor of externalizing problems and fathering of inhibition, with more
      negative mothering in the 2nd and 3rd year forecasting higher CBCL-externalizing
      scores and less negative fathering in the 2nd and 3rd year and more positive
      fathering in the 2nd year forecasting more inhibition at age 3 Implications of
      these findings for studies of parental influence are considered.

PMID- 9635227
TI  - Academic and emotional functioning in early adolescence: longitudinal relations,
      patterns, and prediction by experience in middle school.
AB  - Adopting a motivational perspective on adolescent development, these two
      companion studies examined the longitudinal relations between early adolescents'
      school motivation (competence beliefs and values), achievement, emotional
      functioning (depressive symptoms and anger), and middle school perceptions using
      both variable- and person-centered analytic techniques. Data were collected from
      1041 adolescents and their parents at the beginning of seventh and the end of
      eight grade in middle school. Controlling for demographic factors, regression
      analyses in Study 1 showed reciprocal relations between school motivation and
      positive emotional functioning over time. Furthermore, adolescents' perceptions
      of the middle school learning environment (support for competence and autonomy,
      quality of relationships with teachers) predicted their eighth grade motivation,
      achievement, and emotional functioning after accounting for demographic and prior
      adjustment measures. Cluster analyses in Study 2 revealed several different
      patterns of school functioning and emotional functioning during seventh grade
      that were stable over 2 years and that were predictably related to adolescents'
      reports of their middle school environment. Discussion focuses on the
      developmental significance of schooling for multiple adjustment outcomes during
      adolescence.

PMID- 9635228
TI  - Family systems and adolescent development: shared and nonshared risk and
      protective factors in nondivorced and remarried families.
AB  - The primary goal of this research is to increase the goodness-of-fit between the
      theoretical tenets of family systems theory and quantitative methods used to test
      systems hypotheses. A family systems perspective is applied to two specific
      research questions concerning family influences on adolescent development: To
      what extent are familial risk and protective factors for psychopathology and
      competence shared or not shared by siblings and are different family relationship
      patterns associated with optimal adolescent adjustment in nondivorced and
      remarried families? Multirater and multimethod data from a national sample of 516
      nondivorced and remarried families from the Nonshared Environment and Adolescent
      Development (NEAD) project were examined using a combination of cluster, factor,
      and regression analyses. Results indicated that the effects of an individual
      relationship on adolescent adjustment is moderated by the larger network of
      relationships in which it is embedded. Evidence for nonshared familial processes
      in predicting adolescent psychopathology was also found but only in a subset of
      families, and the mechanisms of influence were neither main effects nor linear,
      as has been assumed by research to date. Results are discussed in light of family
      systems models of relationship influence on development. These results illustrate
      how family systems theory provides a specific example of contextualism as regards
      the development of psychopathology in adolescence.

PMID- 9635229
TI  - Integrating qualitative and quantitative methods in the study of developmental
      psychopathology in context.
AB  - Qualitative methods are well suited to advance the understanding of the role of
      social context in the development of maladaptation and psychopathology. However,
      they have not been widely used by developmental psychopathologists, despite being
      utilized in related fields, particularly in the sociological study of crime and
      delinquency. This article assesses the potential for the increased use of
      qualitative methods in developmental psychopathology and addresses the challenges
      involved in integrating them with quantitative research strategies. The interplay
      of qualitative and quantitative methods in the study of juvenile delinquency is
      reviewed for relevant lessons about both the utility and the difficulties of
      integrating the two types of methods. The problem of assessing continuities and
      discontinuities over the life course in patterns of antisocial behavior is
      discussed as an example of the challenge of integrating methodological paradigms.
      Schools of thought about qualitative methods and their relationship to
      quantitative research paradigms are identified and compared. Examples are
      discussed of narrative life history interviewing and qualitative observational
      techniques and of recent research endeavors integrating these qualitative
      techniques with quantitative data analyses.

PMID- 9635230
TI  - The design and analysis of longitudinal studies of development and
      psychopathology in context: statistical models and methodological
      recommendations.
AB  - The utility and flexibility of recent advances in statistical methods for the
      quantitative analysis of developmental data--in particular, the methods of
      individual growth modeling and survival analysis--are unquestioned by
      methodologists, but have yet to have a major impact on empirical research within
      the field of developmental psychopathology and elsewhere. In this paper, we show
      how these new methods provide developmental psychopathologists with powerful ways
      of answering their research questions about systematic changes over time in
      individual behavior and about the occurrence and timing of life events. In the
      first section, we present a descriptive overview of each method by illustrating
      the types of research questions that each method can address, introducing the
      statistical models, and commenting on methods of model fitting, estimation, and
      interpretation. In the following three sections, we offer six concrete
      recommendations for developmental psychopathologists hoping to use these methods.
      First, we recommend that when designing studies, investigators should increase
      the number of waves of data they collect and consider the use of accelerated
      longitudinal designs. Second, we recommend that when selecting measurement
      strategies, investigators should strive to collect equatable data prospectively
      on all time-varying measures and should never standardize their measures before
      analysis. Third, we recommend that when specifying statistical models,
      researchers should consider a variety of alternative specifications for the time
      predictor and should test for interactions among predictors, particularly
      interactions between substantive predictors and time. Our goal throughout is to
      show that these methods are essential tools for answering questions about life
      span developmental processes in both normal and atypical populations and that
      their proper use will help developmental psychopathologists and others illuminate
      how important contextual variables contribute to various pathways of development.

PMID- 9635231
TI  - Evaluation of a colorimetric method for detecting amphotericin B-resistant
      Candida isolates.
AB  - Substitution of Antibiotic Medium 3 for RPMI 1640 in the microdilution variant of
      M27-A has been proven to permit detection of amphotericin B-resistant Candida
      isolates. For this purpose, we have studied the utility of the colorimetric
      indicator alamarBlue to simplify the former process because it is a readily
      available commercial system. When used in combination with the NCCLS-recommended
      RPMI 1640, alamarBlue did not improve the ability of RPMI 1640 to detect
      resistant isolates. When used in combination with Antibiotic Medium 3, alamarBlue
      reduced discrimination between susceptible and resistant isolates by increasing
      the MIC of susceptible isolates. Thus, alamarBlue does not improve detection of
      amphotericin B resistance among Candida isolates.

PMID- 9635232
TI  - An increase in the number of polymorphonuclear leukocytes inoculated on shell
      vial culture increases the sensitivity of this assay in the detection of
      cytomegalovirus in the blood of immunocompromised patients.
AB  - A prospective study was conducted comparing the sensitivity of the pp65
      antigenemia assay (AGA) to that of the shell-vial culture (SVC) inoculated with
      increasing quantities of polymorphonuclear leukocytes (PMNLs) in the detection of
      cytomegalovirus (CMV) in peripheral blood. From the cellular suspension, three
      SVCs were inoculated with 200,000, 400,000, and 800,000 PMNLs, respectively. Of
      the 201 patients studied, 67 (31.9%) had positive results in one of the two
      analytic tests (AGA or SVC). In this group, 13 (19.4%) presented a negative AGA
      assay; 13 (19.4%) an AGA of 1; 13 (19.4%) an AGA of between 2 and 5; and 28
      (41.8%) an AGA with a value > 6 PMNL-positive x 100,000 PMNLs. The SVC inoculated
      with 200,000 PMNLs detected the presence of CMV in 42 cases (62.6%); 55 (82%)
      with 400,000; and 64 (95.5%) with 800,000. Statistically significant differences
      were observed between the isolation capacities of the SVC inoculated with 200,000
      and 400,000, and the SVC inoculated with 800,000 PMNLs (p = 0.0001). In the
      comparison of the overall sensitivity of the AGA with that of the SVC with
      200,000, the AGA was found to be significantly more sensitive (p = 0.0052). When
      comparing with the SVC with 400,000 PMNLs, the two techniques were found to be
      equally sensitive; and in the comparison with the SVC with 800,000, the culture
      displayed a greater detection sensitivity (p = 0.0023). According to these
      results, it seems evident that the increase in the absolute number of PMNLs
      inoculated in the SVC leads to a significant increase in the sensitivity of the
      SVC in the detection of low-level viremia by CMV.

PMID- 9635233
TI  - Mucoid encapsulated Enterococcus faecalis: an emerging morphotype isolated from
      patients with urinary tract infections.
AB  - Three strains of encapsulated Enterococcus faecalis, which produced highly mucoid
      coalescing colonies on routine bacteriologic media, were isolated from urine
      specimens of patients with urinary tract infection. Encapsulation could be
      demonstrated through India ink preparations. The occurrence of this unusual
      enterococcal colony morphotype, which resembles that of a Gram-negative
      bacterium, may delay true identification.

PMID- 9635234
TI  - Etiology and risk factors of 180 cases of native valve endocarditis. Report from
      a 5-year national prospective survey in Slovak Republic.
AB  - Risk factors, etiology, and outcome of 180 cases of infective endocarditis (IE)
      in the Slovak Republic for 5 years were prospectively studied in a national
      survey. According to the Duke Endocarditis Service Criteria (1994), 169 cases
      were considered definitive and 21 possible/probable. The aortic valve was
      infected in 46.7%, mitral in 47.2%, and tricuspidal/pulmonary in 6.1% of cases.
      The majority of endocarditis cases was caused by Staphylococcus aureus and
      coagulase-negative staphylococci (CNS) (33.3%); only 12.2% were due to viridans
      streptococci; 11.7% were due to Enterococcus faecalis; 6.1% due to Haemophilus
      spp.; 10.1% due to other organisms; and 26.7% were culture negative. Single
      positive cultures of CNS were not considered clinically significant. More than
      25% of 180 patients were older than 60 years. Rheumatic fever was a risk factor
      in 35.5%, dental surgery in 20.5%, prior cardiosurgery in 7.8%, and neoplasia in
      6.7%. All patients were treated with antimicrobials (average length of therapy
      was 29.5 days) and 33.3% of patients also had surgery (valvular prosthesis
      replacement). Forty (22.2%) died, and 140 (77.8%) survived at day 60 after the
      diagnosis of endocarditis was made. All 40 deaths were attributable to infection.
      Univariate analysis comparing deaths and survivors did not show significant
      differences in most of the recorded risk factors between both groups, except age
      > 60 (40.0% versus 21.4%, p < 0.05), staphylococcal etiology (55.0% versus 27.1%,
      p < 0.04), and antibiotic therapy < 21 days (without surgery) (65.0% versus 3.6%,
      p < 0.01). These risk factors were significantly more frequently associated with
      deaths. Viridans streptococcal IE and surgical therapy in addition to antibiotics
      were associated with lower mortality in comparison to staphylococcal endocarditis
      (p < 0.045) or to cases treated with antibiotics only (p < 0.05). In comparison
      to other nationally based surveys in Europe (Greece, Croatia, France), the
      percentage of culture-negative endocarditis and spectrum of pathogens differed
      significantly.

PMID- 9635235
TI  - Antimicrobial activity of quinupristin-dalfopristin (RP 59500, Synercid) tested
      against over 28,000 recent clinical isolates from 200 medical centers in the
      United States and Canada.
AB  - A total of 200 medical center laboratories in the USA and Canada contributed
      results of testing quinupristin-dalfopristin, a streptogramin combination
      (formerly RP 59500 or Synercid), against 28,029 Gram-positive cocci. Standardized
      tests [disk diffusion, broth microdilution, Etest (AB BIODISK, Solna, Sweden)]
      were utilized and validated by concurrent quality control tests. Remarkable
      agreement was obtained between test method results for characterizing the
      collection by the important emerging resistances: 1) oxacillin resistance among
      Staphylococcus aureus (41.0 to 43.7%); 2) vancomycin resistance among
      Enterococcus faecium (50.0 to 52.0%); and 3) the penicillin nonsusceptible rate
      for pneumococci (31.1% overall, with 10.6% at MICs of > or = 2 micrograms/mL).
      The quinupristin-dalfopristin MIC90 for oxacillin-susceptible and -resistant S.
      aureus was 0.5 microgram/mL and 1 microgram/mL, respectively. The quinupristin
      dalfopristin MIC90 for vancomycin-resistant E. faecium was 1 microgram/mL, and
      only 0.2% of isolates were resistant. Other Enterococcus species were generally
      not susceptible to the streptogramin combination but were usually inhibited by
      ampicillin (86 to 97% susceptible; MIC50, 1.0 microgram/mL) or vancomycin (86 to
      95%; MIC50, 1.0 microgram/mL). Among all tested enterococci, the rate of
      vancomycin resistance was 16.2%. The quinupristin-dalfopristin MIC90 (0.75
      microgram/mL) for 4,626 tested Streptococcus pneumoniae strains was not
      influenced by the penicillin or macrolide susceptibility patterns. When five
      regions in the USA and Canada were analyzed for significant streptogramin and
      other antimicrobial spectrum differences, only the Farwest region had lower
      numbers of streptogramin-susceptible E. faecium. Canadian strains were generally
      more susceptible to all drugs except chloramphenicol and doxycycline when tested
      against E. faecalis (73% and 89% susceptible, respectively). The U.S. Southeast
      region had S. pneumoniae strains less susceptible to macrolides (73%) but had
      more susceptibility among E. faecium isolates tested against vancomycin and
      ampicillin. The Northeast region of the USA had the greatest rate of vancomycin
      resistance among enterococci. Strains retested by the monitor because of
      quinupristin-dalfopristin resistance (MICs, > or = 4 micrograms/mL) were
      generally not confirmed (2.2% validation), and only 0.2% of E. faecium isolates
      were identified as truly resistant. The most common errors were: 1) species
      misidentification (28.0%); 2) incorrect susceptibility results (65.6%); and 3)
      mixed cultures (4.3%) tested by participants. Overall, quinupristin-dalfopristin
      was consistently active (> or = 90% susceptible) against major Gram-positive
      pathogens in North America, regardless of resistance patterns to other drug
      classes and geographic location of their isolation.

PMID- 9635236
TI  - Epidemiology, laboratory detection, and therapy of penicillin-resistant
      streptococcal infections.
AB  - Streptococci cause a wide range of infections in humans including respiratory
      tract infections, endocarditis, meningitis, bacteremias, and skin and soft tissue
      lesions. Mutations in the penicillin binding proteins target sites in these
      organisms have recently caused resistance to penicillins and cephalosporins. The
      passage of resistant genetic material from one streptococcal species to another
      has been recognized as one of the mechanisms by which this resistance has
      occurred and spread. Such resistance has been a particular problem in
      Streptococcus pneumoniae and viridans group streptococci with penicillin
      resistance levels in excess of 25%, now common in both groups of organisms
      worldwide. Fourth-generation cephalosporins, with their enhanced antibacterial
      activity against Gram-positive organisms (cefpirome > cefepime) and their
      increased stability to the beta-lactamases produced by many bacterial species,
      offer a new option for the treatment of potentially life-threatening infections
      such as pneumococcal pneumonia and meningitis with or without bacteremia.
      Clinical trials are currently in place to evaluate the role of these agents in
      these, and other, indications of Gram-positive infections. Prior studies of
      cefpirome therapy for infections caused by Streptococcus spp. were successful,
      and recent expanded in vitro investigations profess a future for expanded use of
      cefpirome to treat infections produced by several Gram-positive species.

PMID- 9635237
TI  - Important and emerging beta-lactamase-mediated resistances in hospital-based
      pathogens: the Amp C enzymes.
AB  - Resistance to third-generation cephalosporins mediated by beta-lactamases is an
      increasing problem for clinical therapeutics. A wide range of Enterobacteriaceae
      produce these AmpC enzymes (Bush-Jacoby-Medeiros group 1), including Enterobacter
      spp., Citrobacter freundii, Morganella morganii, Providencia spp., and Serratia
      marcescens. Resistance via this mechanism has been shown to be statistically
      correlated with the use of some third-generation cephalosporins, and the
      infections caused by these stably derepressed enzyme-producing species seem to
      occur most frequently in the seriously ill. More recently the genes encoding this
      enzyme have been documented on plasmids capable of transfer into other species
      such as Klebsiella pneumoniae. Fourth-generation cephalosporins, with stability
      and low affinity for the Amp C beta-lactamases and the ability to penetrate
      rapidly into the periplasmic space of Gram-negative organisms, offer a viable
      alternative in the treatment of these infections or as empiric regimens.
      Furthermore, these compounds (example: cefpirome) possess greater potency against
      the frequently occurring Gram-positive cocci such as oxacillin-susceptible
      staphylococci and the streptococci (including some penicillin-resistant strains)
      as compared to previously used anti-pseudomonal cephalosporias, ceftazidime.

PMID- 9635238
TI  - Empiric therapy of bacterial infections in patients with severe neutropenia.
AB  - The urgent need to treat presumptive infections in neutropenic patients has meant
      that initial therapy is empiric based on the pathogens most likely to be
      responsible for the patient's rise in temperature or other symptoms of infection.
      The spectrum of causative pathogens has changed over time and reflects the
      availability and use of antimicrobial agents. Gram-positive organisms
      predominated in the 1940s and onward until the widespread use of early
      penicillins and cephalosporins effectively addressed this problem. The upsurge in
      infections in the 1970s and 1980s caused by Gram-negative organisms, particularly
      Pseudomonas aeruginosa, Escherichia coli and Klebsiella spp., has been supplanted
      by a new wave of infections caused by Gram-positive organisms, this time
      predominantly Staphylococcus aureus, Staphylococcus epidermidis, and the viridans
      streptococci. The fourth-generation cephalosporins (cefpirome) among other broad
      spectrum beta-lactams, by virtue of their enhanced antimicrobial activity against
      Gram-positive pathogens and greater beta-lactamase stability, are promising
      candidates for use in the empiric management of febrile episodes in neutropenic
      patients. Early clinical trial results are promising and should lead the way for
      further use of these compounds in this indication.

PMID- 9635239
TI  - The role of fourth-generation cephalosporins in the treatment of serious
      infectious diseases in hospitalized patients.
AB  - For many years, the third-generation cephalosporins have been utilized in the
      treatment of a broad range of infections. The reduction in the efficacy of these
      antimicrobials in hospitals seen in recent years is a result of the development
      of resistance to these compounds. This resistance, caused in part by the
      production of beta-lactamases which can spread from species to species, has
      intensified the search for alternative agents. Compared with third-generation
      cephalosporins, fourth-generation cephalosporins possess enhanced activity
      against Gram-positive organisms, excellent penetration into Gram-negative
      bacilli, and are more stable against the activity of some beta-lactamases.
      Accordingly, fourth-generation cephalosporins are attractive candidates to
      replace third-generation cephalosporins for the treatment of many nosocomial
      infections.

PMID- 9635240
TI  - The clinical potential of fourth-generation cephalosporins.

PMID- 9635241
TI  - In vitro bactericidal activity of cefpirome in combination with vancomycin
      against Staphylococcus aureus and coagulase-negative Staphylococcus.

PMID- 9635242
TI  - In vitro activities of six extended spectrum beta-lactam antibiotics against
      clinically significant gram-negative bacteria.

PMID- 9635243
TI  - Cefpirome: epidemiological survey in intensive care units and hematological units
      in The Netherlands. The Dutch Study Group.

PMID- 9635244
TI  - In vitro evaluation of cefpirome: an Australasian study of isolates from
      intensive care unit and hematology/oncology patients. The Cefpirome Study Group.

PMID- 9635245
TI  - Clinical studies of cefpirome in the treatment of urinary tract infections caused
      by Enterococcus faecalis.

PMID- 9635246
TI  - Cefpirome versus ceftazidime as empirical sepsis treatment. The Study Group.

PMID- 9635247
TI  - In vitro activity of cefpirome against Streptococcus pneumoniae strains with
      decreased susceptibility to cefotaxime.

PMID- 9635248
TI  - Lung injury and degradation of extracellular matrix components by Aspergillus
      fumigatus serine proteinase.
AB  - Aspergillus fumigatus produces a variety of extracellular proteinases that are
      believed to be virulence factors towards Aspergillus-related lung disease. Among
      Aspergillus proteinases, the serine proteinase is thought to play a major
      virulent role because of its widespread production. Nevertheless, evidence of
      direct pulmonary injury caused by the A. fumigatus serine proteinase is still
      lacking. The purpose of our work was: (1) to provide evidence for a pivotal role
      of A. fumigatus serine proteinase in producing lung injury in an animal model,
      and (2) to investigate the broadness of the substrate specificity of the
      proteinase towards extracellular matrix components. To achieve this aim, the
      proteinase from an A. fumigatus strain isolated from human airways was purified
      by a four-step procedure, including cation exchange and hydrophobic interaction.
      High-performance capillary electrophoresis, SDS-PAGE, determination of K(m)
      towards synthetic substrates, and inhibitory studies were used to further
      characterize the A. fumigatus serine proteinase. With reference to extracellular
      matrix components, the A. fumigatus serine proteinase was shown to degrade human
      lung elastin at a higher rate than an equimolar amount of human neutrophil
      elastase. Human lung collagen, type I and type III collagens, as well as
      fibronectin, were quickly digested by the A. fumigatus serine proteinase.
      Finally, mice intratracheally injected with the proteinase showed a significant
      degree of lower respiratory tract destruction. We conclude that the A. fumigatus
      serine proteinase is capable per se of hydrolyzing the major structural barriers
      of the lung.

PMID- 9635249
TI  - Differential expression of arginase and iNOS in the lung in sepsis.
AB  - The primary metabolic fates of L-arginine are conversion to L-citrulline by
      nitric oxide synthase (NOS) and to L-ornithine by arginase. In the lung, arginine
      utilization is increased after the inducible form of NOS (iNOS) is expressed
      during inflammation. The expression of arginase in normal lung and after sepsis,
      and its potential relationships with iNOS, however, are not known. Since arginase
      and iNOS share the substrate L-arginine, we tested the hypothesis that lung
      arginase would be co-induced with iNOS in sepsis and its cellular distribution
      would be related to that of iNOS in the lung. Lungs from cecal ligation and
      puncture (CLP) and sham-operated (S) rats were harvested 6 or 16 hours after the
      procedures. Lung wet-to-dry weight ratio, myeloperoxidase content, and lipid
      peroxidation products were measured as indices of lung injury. Western blot
      analyses were performed with polyclonal antibodies against two isoforms of rat
      arginase (I and II) and iNOS. Additional lungs from CLP and S animals were
      inflation-fixed for immunohistochemistry using the same antibodies. We found by
      Western blot that arginase II at 39 kDa was the main isoform present in normal
      rat lung. The enzyme was distributed diffusely in alveolar and bronchial
      epithelial cells, endothelial cells, and alveolar macrophages. After CLP,
      arginase II was almost undetectable in rat lungs at 16 hours. In contrast, in
      normal lung, the iNOS was not detectable by Western blot or immunohistochemistry.
      After CLP, strong expression of iNOS was found in similar cell types to arginase
      II. These data demonstrate loss of constitutive expression of arginase II in rat
      lung as iNOS is upregulated by the response to sepsis.

PMID- 9635250
TI  - Kinetic characterization of bovine lung low-molecular-weight protein tyrosine
      phosphatase.
AB  - Protein tyrosine phosphatase is an important class of enzymes that plays an
      essential role in the cellular proliferation, differentiation, and oncogenesis.
      In this paper we report characterization of a low-molecular-weight protein
      tyrosine phosphatase purified from bovine lung. The enzyme activity was
      essentially independent of metal ions and sensitive to sulfhydryl reagents. Both
      vanadate and inorganic phosphate are competitive inhibitors, with Ki values of
      0.38 microM and 0.28 mM, respectively. Besides p-nitrophenyl phosphate, the
      enzyme was also able to efficiently hydrolyze tyrosine phosphate, beta-naphthyl
      phosphate, and flavine mononucleotide.

PMID- 9635251
TI  - Posttreatment with eicosatetraynoic acid decreases lung edema in guinea pigs
      exposed to phosgene: the role of leukotrienes.
AB  - Acetylenic acids such as 5,8,11,14-eicosatetraynoic acid (ETYA), have been shown
      to be effective in preventing pulmonary edema formation (PEF). In phosgene
      exposed guinea pigs, we examined the effects of ETYA on PEF, measured as real
      time lung weight gain (lwg). Pulmonary artery pressure (Ppa), airway pressure
      (Paw), perfusate leukotrienes (LT) C4/D4/E4/B4, and lung tissue lipid
      peroxidation (TBARS) were measured using the isolated, buffer-perfused lung
      model. Guinea pigs were challenged to 175 mg/m3 (44 ppm) phosgene for 10 minutes
      giving a concentration x time product of 1750 mg.min/m3 (437 ppm.min). Five
      minutes after removal from the exposure chamber, guinea pigs were treated, i.p.,
      with 200 microL of 100 microM ETYA. 200 microL of 50 microM ETYA was added to the
      perfusate every 40 minutes, beginning at 60 minutes after start of exposure (t =
      0). There were four groups in this study: air-treated, phosgene-exposed, ETYA
      posttreated + phosgene, and ETYA-posttreated + air ETYA-posttreated + phosgene
      guinea pigs had significantly lower Ppa (P = .006), Paw (P = .009), and lwg (P =
      .016) compared with phosgene-exposed animals. Phosgene exposure reduced LTB4
      compared with air-treated controls (P = .09). ETYA-posttreatment + phosgene had
      significantly increased perfusate LTB4 (P = .0006) compared with phosgene
      exposure only group. Total perfusate, LTC4 + LTD4 + LTE4, was not different
      between phosgene-exposed, air-treated or ETYA-posttreatment + phosgene over time.
      Posttreatment with ETYA significantly lowered TBARS formation, 206 +/- 13 versus
      285 +/- 23 nmol/mg protein (P = .016), compared with phosgene-exposed lungs.
      Paradoxically, ETYA posttreatment decreased PEF and lipid peroxidation, but
      increased sulfidopeptide LT release from the lung during perfusion. We conclude
      that LTC4/D4/E4, and B4, may play different roles than previously thought for PEF
      in the isolated perfused lung model.

PMID- 9635252
TI  - Silica deposition in the lung during epithelial injury potentiates fibrosis and
      increases particle translocation to lymph nodes.
AB  - Increased respiratory disease and daily mortality rates are associated with
      higher levels of fine particulate air pollutants. We examined the possibility
      that deposition of particles to previously injured lungs might accentuate
      pulmonary damage, by investigating how the lung handled silica deposited during a
      phase of epithelial injury. A low dose of intratracheal (i.t.) bleomycin (BL) was
      used to induce epithelial damage in mice; 3 days later, 0.2 mg silica was
      instilled. Lung injury, measured by cell numbers and protein levels in
      bronchoalveolar lavage, was increased at 1 week and many silica particles
      translocated to the interstitium. At 12 weeks, the silica plus BL group showed
      increased pulmonary fibrosis biochemically and morphologically, and had
      significantly higher retained-silica content in the lung. In addition, these mice
      showed enlarged hilar lymph nodes with many granulomas-containing macrophages and
      silica. The results indicate that instillation of fine particulates to the
      alveoli at a time of epithelial damage potentiates the lung injury and increases
      translocation of particles to the interstitium. In the case of silica, deposition
      of particles into injured lungs resulted in increased fibrosis. The demonstration
      of enhanced translocation of silica to lymph nodes suggests that inhaled fine
      particulates may induce more distal effects following transport across an injured
      epithelium and subsequent entrance to the lymphatic system.

PMID- 9635253
TI  - Adhesive characteristics of type II pneumocyte subpopulations from saline- and
      silica-treated rats.
AB  - Alveolar epithelial cells isolated from silica-treated rat lungs provide a system
      for the in vitro study of repair mechanisms. In studies of type II cell
      interactions with the extracellular matrix, we observed that type IIB pneumocytes
      from silica-treated rats adhered to tissue culture plastic more readily than do
      normal type II cells. This paper examines the adhesion characteristics of IIA and
      IIB cells and their modulation by divalent cations. We describe differences in
      the adhesive behavior of two subpopulations of freshly isolated type II
      pneumocytes from saline- and silica-treated rats. The observations have
      implications for repair and tissue remodeling in the lung.

PMID- 9635254
TI  - Alterations in the expression of chemokine mRNA levels in fibrosis-resistant and 
      sensitive mice after thoracic irradiation.
AB  - Fibrosis, characterized by the accumulation of collagen, is a consequence of a
      chronic inflammatory response. The purpose of this study was to determine if the
      mRNA expression of the chemokines, lymphotactin (Ltn), RANTES, eotaxin,
      macrophage inflammatory protein (MIP)-1 alpha, -1 beta, and -2, interferon
      inducible protein 10 (IP-10), and monocyte chemotactic protein-1 (MCP-1), are
      altered during the development of radiation-induced pneumonitis and fibrosis.
      Further, we wished to determine if these changes differ between two strains of
      mice that vary in their sensitivity to radiation fibrosis. Fibrosis-sensitive
      (C57BL/6) and fibrosis-resistant (C3H/HeJ) mice were irradiated with a single
      dose of 12.5 Gy to the thorax. Total lung RNA was prepared and hybridized
      utilizing RNase protection assays. Data were quantified by phosphorimaging and
      results normalized to a constituitively expressed mRNA L32. 8 weeks post
      irradiation most chemokines measured were elevated to varying degrees. The degree
      of elevation of each chemokine was identical in both strains. This suggested that
      chemotactic activity for neutrophils, macrophages, and lymphocytes were occurring
      during pneumonitis. By 26 weeks post-irradiation, messages encoding Ltn, RANTES,
      IP-10, and MCP-1 were elevated only in fibrosis sensitive (C57BL/6) mice. In situ
      hybridization demonstrated that MCP-1 and RANTES transcripts were produced
      predominantly from macrophages and lymphocytes. These studies suggest that
      lymphocytic recruitment and activation are key components of radiation-induced
      fibrosis.

PMID- 9635255
TI  - Effect of developmental age and hyperoxia exposure on kinase and phosphatase
      activities in newborn rat lungs.
AB  - To better understand the biochemical events accompanying lung alveolarization and
      development, we studied the specific activity of the cAMP-dependent protein
      kinase (PKA) and the type 2A protein phosphastase (PP2A), and the activity and
      protein content of the calcium- and lipid-dependent protein kinase (PKC) in
      cytosolic preparations of lungs. Lungs were obtained from rat pups on day 2 of
      life and on days 7, 14, and 27 from pups exposed to hyperoxia (> 95% O2, days 4
      14; 65% O2 days 15-27) or normoxia from day 4 onwards. There were no significant
      changes in PKA specific activity with developmental age or hyperoxic exposure.
      PKC specific activity increased significantly (P < .05) in normoxic animals from
      day 2 (64 +/- 13.5 pmol phosphate released/min/mg protein) to day 14 (105 +/- 9).
      The increase was sustained to day 27. There was no effect on PKC activity due to
      hyperoxia alone (ANOVA). This increase in PKC activity was accompanied by an
      increase in the mass of the delta, epsilon and zeta isoforms of PKC in normoxic
      pups. The gamma isoform of PKC was undetectable in all samples whereas the alpha
      and beta isoforms were detectable but showed no changes with developmental age.
      PP2A specific activity increased significantly (P < .05) from 13.3 +/- 0.5 nmol
      phosphate released/min/mg protein on day 2 to 17.7 +/- 0.9 on day 7 in normoxic
      pups, then returned to day 2 level at advanced developmental age. Hyperoxia
      exposure prevented the increase in enzyme activity observed on day 7 in normoxic
      animals. These data suggest that protein phosphorylation may be one mechanism by
      which alveolarization is regulated in developing lungs.

PMID- 9635256
TI  - Expression of nitric oxide synthase isoforms in normal human tracheobronchial
      epithelial cells in vitro: dependence on retinoic acid and the state of
      differentiation.
AB  - The retinoic acid (RA) and differentiation dependence of constitutive expression
      of the nitric oxide synthase (NOS) isoforms, iNOS, eNOS, and bNOS, was examined
      by reverse transcriptase polymerase chain recitation (RT-PCR) in cultured,
      normal, human, tracheobronchial epithelial (NHTBE) cells. In the presence of RA
      (RA+), early passage NHTBE cells grown in air-liquid interface (ALI) cultures
      undergo mucous differentiation; in the absence of RA (RA-), they undergo
      metaplastic squamous differentiation. Under both conditions the respective
      differentiated phenotype develops around day 10 of culture. We found that iNOS
      mRNA levels were much higher in RA+ cultures, expressing the mucous phenotype,
      than in RA- cultures, expressing the metaplastic squamous phenotype. In contrast,
      eNOS mRNA levels were much higher in RA- cultures than in RA+ cultures.
      Expression of bNOS was not significantly affected by the RA status. The pattern
      of expression of NOS isoforms was then studied during the course of development
      of the two cellular phenotypes. During the early stages of differentiation,
      expression of iNOS (RA+) and eNOS (RA-) was very low, indicating that the
      expression of these two isoforms was not only dependent on the presence or
      absence of RA, but also on the degree of differentiation. The differentiation
      dependence of bNOS mRNA was less obvious. Four days of RA treatment of RA-
      cultures, which reverses the squamous phenotype and restores mucous
      differentiation, induced iNOS expression in a concentration-dependent manner.
      eNOS expression was depressed by 10(-8) M RA, while bNOS mRNA levels were
      slightly reduced by 10(-6) M RA. No NOS proteins were detected in unstimulated
      RA+ and RA- cultures. iNOS protein was induced by cytokine treatment in RA+
      cultures, in contrast to eNOS and bNOS protein levels, which were unaffected. Our
      studies show that constitutive expression of the NOS isoforms is differentially
      regulated and that iNOS and eNOS mRNA levels are dependent on the stage of mucous
      and squamous differentiation, respectively. bNOS expression was only marginally
      affected by the RA or differentiation status.

PMID- 9635257
TI  - Pregnancy plans despite AIDS risk.

PMID- 9635258
TI  - Is Medicaid pronatalist? The effect of eligibility expansions on abortions and
      births.
AB  - CONTEXT: Income thresholds for Medicaid eligibility for pregnant women were
      raised in two phases between 1987 and 1991. During roughly the same period, the
      U.S. fertility rate rose and the abortion rate declined; changes were
      particularly marked among young women, raising the possibility that fertility
      increases were related to Medicaid expansions. METHODS: Pooled time-series cross
      section regressions were used to examine the effects of the Medicaid eligibility
      expansions in 15 states on rates of abortions and births among unmarried women
      aged 19-27 with 12 or fewer years of schooling. Abortion data came from the
      National Center for Health Statistics or state health departments and were
      aggregated by women's age, race, marital status and schooling; data on births
      were from national natality tapes. RESULTS: The Medicaid expansions were
      associated with a 5% increase in the birthrate among white women, but did not
      influence the rate among black women. Overall, no effect on the abortion rate was
      evident, but in analyses restricted to a subsample of eight states with the most
      complete abortion data, the rate among white women showed a significant decline
      after the second phase of expansions. CONCLUSIONS: Subsidized health care for low
      income pregnant women in these 15 states may have encouraged white women to have
      more children than they would have without coverage.

PMID- 9635259
TI  - Contraceptive practices and trends in France.
AB  - CONTEXT: Contraceptive use has been legal in France for the past 30 years, and
      patterns of use changed substantially from the 1960s to the 1980s. Given the
      rapidity with which use patterns change and the possible impact of rising concern
      about infection with HIV and other sexually transmitted diseases, it is important
      to determine trends of contraceptive practice into the 1990s. METHODS: A total of
      5,900 French households were selected in 1994 for inclusion in the Fertility and
      Family Survey. Respondents were questioned about their contraceptive use patterns
      and family formation status. The results were compared with those of comparable
      surveys conducted in 1978 and 1988. RESULTS: Two-thirds of French women used some
      form of reversible contraceptive method in 1994. Oral contraceptive use has grown
      steadily in France: About 40% of women aged 20-44 reported using the pill alone
      or combined with another method in 1994, compared with 34% in 1988 and 28% in
      1978. Condom use has also been on the rise: Nearly 8% of women were using condoms
      alone or combined with another method in 1994, up from 5% in 1988 and 6% in 1978.
      IUD use has declined from 19% in 1988 to 16% in 1994, and both male and female
      sterilizations remain rare. CONCLUSIONS: Contraceptive behavior in France appears
      unique among developed countries, with fairly high levels of oral contraceptive
      use--even among older women--relatively high levels of IUD use and little
      reliance on either male or female sterilization. As with other countries,
      however, condom use has climbed in recent years, and is especially common at
      first intercourse.

PMID- 9635260
TI  - Gender and ethnic differences in the timing of first sexual intercourse.
AB  - CONTEXT: Whether the effect of gender on the risk of first intercourse in
      influenced by adolescents ethnicity has received limited attention in research on
      age at first sex. Such information could provide a more complete understanding of
      adolescent sexual behavior. METHODS: Life-table analysis using data from a
      population-based, ethnically diverse sample of 87/Los Angeles County youths was
      employed to estimate the median age at first sex for each gender-and-ethnicity
      group. Multivariate analysis using proportional hazards techniques was conducted
      to determine the relative risk of sexual activity among teenagers in each group.
      RESULTS: Overall, the teenagers in the sample had a median age at first sex of
      16.9 years. Black males had the lowest observed median (15.0), and Asian American
      males the highest (18.1); white and Hispanic males, and white and black females,
      reported similar ages (about 16.5 years). Hispanic and Asian American females had
      rates of first sex about half that of white females, although these protective
      effects were explained by differences in family structure. Even after controlling
      for background characteristics, black males had rates of first sex that were
      about 3-5 times the rates of the other gender-and-ethnicity groups. In addition,
      Asian American males were less likely than Hispanic males to be sexually
      experienced, and Hispanic males had almost twice the rates of sexual activity of
      Hispanic females. CONCLUSIONS: Socioeconomic conditions account for ethnic
      differences among females in the age at first sex, and cultural influences may
      contribute to the difference between Hispanic males and females; explanations for
      black males, however, remain elusive.

PMID- 9635261
TI  - Measuring the extent of abortion underreporting in the 1995 National Survey of
      Family Growth.
AB  - CONTEXT: Induced abortions are often severely underreported in national surveys,
      hampering the estimation and analysis of unintended pregnancies. To improve the
      level of abortion reporting, the 1995 National Survey of Family Growth (NSFG)
      incorporated new interview and self-report procedures, as well as a monetary
      incentive to respondents. METHODS: The weighted numbers of abortions reported in
      the main interview of the 1995 NSFG (Cycle 5), in the self-report and in the two
      procedures combined are compared with abortion estimates from The Alan Guttmacher
      Institute. The Cycle 5 estimates are also compared with estimates from previous
      cycles of the NSFG. RESULTS: The self-report produces better reporting than the
      main interview, but combining data from the two procedures yields the highest
      count of abortions. For the period 1991-1994, the level of reporting is 45% in
      the main interview, 52% in the self-report and 59% when the two methods are
      combined. The level of abortion reporting in the combined data ranges from 40%
      for women with an income less than the federal poverty level to more than 75%
      among women who were older than 35, those who were married at the time of their
      abortion and those with an income above 200% of the poverty level. The
      completeness of abortion reporting in the main interview of Cycle 5, though
      indicating a remarkable improvement over reporting in Cycle 4, is comparable to
      the levels in Cycles 2 and 3. CONCLUSIONS: The usefulness of the NSFG remains
      extremely limited for analyses involving unintended pregnancy and abortion.

PMID- 9635262
TI  - Factors influencing the delivery of abortion services in Ontario: a descriptive
      study.
AB  - CONTEXT: Although Canadian women have had the right to obtain legal induced
      abortions for the past decade, access to the procedure is still limited and
      controversial in many areas. METHODS: Chiefs of obstetrics and gynecology, chiefs
      of staff, directors of nursing and other health professionals at 163 general
      hospitals in Ontario, Canada, were asked to provide information on issues
      concerning the availability of abortion services of their facility. The hospital
      participation rate was 97% and the individual response rate was 75%. RESULTS:
      Nearly one-half (48%) of hospitals perform abortions. Approximately 36% of these
      hospitals do so up to a maximum gestational age of 12 weeks, 23% to a maximum of
      13-16 weeks, 37% to a maximum of 17-20 weeks and 4% at greater than 20 weeks.
      Hospital factors, including resources and policies, did not significantly
      influence whether abortions are provided. However, these factors did affect the
      number performed, whether there were gestational limitations and the choice of
      procedure. About 13% of provider hospitals indicated that staff training
      contributes to the existence of gestational age limits, and 24% said that it
      directly influences procedure choice. Only 18% of hospitals reported that their
      physicians have received additional training outside of their medical school or
      medical residency education to learn abortion techniques or to gain new skills.
      Forty-five percent of hospitals that provide abortions had experienced harassment
      within the past two years, and 15% reported that this harassment has directly
      affected their staff members' willingness to provide abortions. CONCLUSION: Based
      upon the provision of obstetric care, many hospitals in Ontario that are capable
      of offering abortion services do not. Some of the reasons for this failure are
      related to the procedure itself, while others may be related to resource issues
      that affect the delivery of other medical services as well. Variation in the
      availability of abortions is due to a shortage of clinicians performing the
      procedure, and training directly influences gestational limits and procedural
      choices.

PMID- 9635263
TI  - Family planning service provision in rural areas: a survey in Washington State.
AB  - CONTEXT: Women in rural areas are highly dependent on public clinics for family
      planning services, yet little information has been collected on rural family
      planning providers, especially on their funding and operation. METHODS: All 31
      family planning clinic sites in rural Washington State were surveyed about their
      sponsorship, staffing, service provision and population coverage. RESULTS: Clinic
      sites were located in 25 of the 53 discrete rural health service areas of
      Washington State. While the three wealthiest areas had clinics, eight of the
      poorest areas had no clinics. Eight clinics were Planned Parenthood affiliates,
      eight were private freestanding clinics and 15 were local health department
      sites. Clinic sites were small (with the equivalent of 2.4 full-time staff
      members, on average) and offered a mean of 18 of 43 potential reproductive and
      women's health care services; general primary care services were rarely provided.
      Only one clinic offered abortions. CONCLUSION: Family planning clinics in rural
      Washington State offer an important but limited number of services. Many rural
      areas have no local family planning clinic. Given these clinics' reliance on
      federal and state funding, decreased public support might seriously impair family
      planning provision in rural areas.

PMID- 9635264
TI  - Studying parental involvement in school-based sex education: lessons learned.

PMID- 9635265
TI  - Approaching clinical application of xenotransplantation.

PMID- 9635266
TI  - Surgical correction of hypertrophic obstructive cardiomyopathy: seventeen-year
      Green Lane experience.
AB  - Between 1977 and 1994, 42 patients were treated surgically for hypertrophic
      obstructive cardiomyopathy (HOCM). Patients have been followed up between 2
      months to 17 years, mean of 107 months. There were 26 (62%) males and 16 (38%)
      females. There was only one pediatric case. There was no correlating factor among
      the ethnic groups (Maori, European, Indian, Asian, etc.). Family history was
      noted in 12% of the cases. Seventy-one percent of patients had aortic/left
      ventricular (LV) combined approach while 29% had aortic approach alone at the
      time of surgery. Five patients underwent other procedures, along with coronary
      artery bypass grafting in 3, mitral valve replacement in 1, and aortic valve
      replacement in 1. Persistent postoperative arrhythmias were found in 7 cases,
      atrial fibrillation (AF) in 3, and left bundle branch block in 4.

PMID- 9635267
TI  - Sinus of Valsalva aneurysms: 20 years' experience.
AB  - BACKGROUND: Aneurysms of sinus of Valsalva are rare. Here, we analyze
      retrospectively patients operated on at our center during the last 20 years.
      PATIENTS AND METHODS: One hundred four cases of congential aneurysm of sinus of
      Valsalva were operated upon between January 1977 and April 1996. Only 12
      aneurysms were unruptured. The majority (76.9%) arose from the right coronary
      sinus. The right ventricle was the most common chamber of rupture (58.6%).
      Ventricular septal defect was associated in 46 patients (44.2%), of which 28
      (60.9%) were supracristal. Ventricular septal defect was more common in aneurysms
      arising from the right coronary sinus (91.3%). Aortic incompetence was found in
      45 patients (43.3%). The defect was closed through the aortic root alone in 24
      patients (23.1%) and through both the aortic root and the chamber of rupture in
      the remaining 80 patients. Six patients underwent aortic valve repair, and 21 an
      aortic valve replacement. RESULTS: There were two hospital deaths (1.92%).
      Morbidities were few. Follow-up ranged from 1 to 20 years (mean 8.2 +/- 1.1).
      There was one late noncardiac death, and in the majority, the long-term follow-up
      was uneventful. CONCLUSION: Surgery for aneurysm of sinus of Valsalva yields
      gratifying results, and it should be undertaken as soon as the condition is
      diagnosed.

PMID- 9635268
TI  - Rapid recovery of octogenarians following coronary artery bypass grafting.
AB  - BACKGROUND: Rapid recovery protocols for coronary artery bypass grafting (CABG)
      have resulted in major decreases in postoperative hospital length of stay (LOS)
      when applied to younger patients undergoing elective procedures. However, the
      effectiveness of rapid recovery protocols when applied to octogenarians has not
      been thoroughly studied. METHODS: Thirty-seven consecutive octogenarians
      underwent isolated CABG utilizing cardiopulmonary bypass (CPB). A protocol
      emphasizing preoperative placement of the intra-aortic balloon pump, reduced CPB
      time, early extubation, perioperative steroids, thyroid hormone, and aggressive
      postoperative diuresis was used. RESULTS: The 30-day operative mortality for the
      entire series was 5.4%. Twenty-five patients (71%, group I) were discharged in <
      10 days postoperatively (average LOS of 6.3 +/- 1.6 days), while ten patients
      (29%, group II) were discharged at 10 or more days postoperatively (average LOS
      of 20.3 +/- 8.0, p < 0.001). Patients in group II were found to have a higher
      incidence of obesity (50% vs 4%, p < 0.01), symptomatic peripheral vascular
      disease (60% vs 8%, p < 0.01), and preoperative ambulatory difficulties (50% vs
      0%, p < 0.01). The incidence of complications was 31% for the entire series, with
      no differences between the groups. CONCLUSION: Octogenarians performed well under
      a rapid recovery protocol, with 71% being discharged in < 10 days
      postoperatively, while patients with obesity, symptomatic peripheral vascular
      disease, and ambulatory difficulties rehabilitated more slowly.

PMID- 9635269
TI  - Right heart growth after the Bjork connection in tricuspid atresia.
AB  - BACKGROUND: Atrioventricular (Bjork) connection used for the correction of
      tricuspid atresia has become of little more than historical interest. However,
      the optimal form of management of patients undergoing this repair still requires
      continued assessment of the long-term outcome. We review our experience with
      valveless atrioventricular connection focusing on the morphological changes seen
      in the heart chambers. METHODS: Between October 1978 and March 1986, seven
      patients with tricuspid atresia having concordant ventriculoarterial connection
      underwent atrioventricular connection. Configuration of the surgical connection
      included Dacron extracardiac conduit without valve insertion. End-diastolic
      volumes were calculated in the respective heart chambers. A group of patients
      undergoing atriopulmonary connection was used as control subjects. RESULTS: The
      diminutive right ventricle showed conspicuous growth at 1.1 +/- 1.1 years after
      the initial repair, with the end-diastolic volume index increasing from 25.0 +/-
      8.7% of normal value at a preoperative state to 80.4 +/- 31.1% of normal value
      postoperatively. Further operation was done in three patients because of the
      obstructive atrioventricular pathway. At reoperation, reconstruction of the
      connection with an addition of either atriopulmonary or cavopulmonary anastomosis
      afforded clinical improvement in our series. CONCLUSIONS: This study suggests
      that volume load resulting from the widely patent atrioventricular connection
      combined with backward regurgitation affects the development of young heart
      muscle of the right ventricle. The optimal choice of surgical strategy should be
      made at reintervention through recognition of the particular postsurgical
      anatomy.

PMID- 9635270
TI  - Variations in annuloplasty ring and sizer dimensions may alter outcome in mitral
      valve repair.
AB  - BACKGROUND AND AIMS: Sizing the mitral annulus remains one of the more subjective
      areas of annuloplasty surgery. We compared the dimensions of annuloplasty rings
      to annuloplasty sizers and to human mitral valve annuli to determine whether any
      discrepancies exist that might impact repair results. METHODS: The anterior and
      posterior length of rigid rings, flexible rings, and corresponding sizers were
      measured. The ratio of the anterior length to the total length was calculated
      (A/T ratio) and compared to normal human ratios. RESULTS: Nearly all rings had
      A/T ratios between 30% and 35% (except for the 32-mm rigid ring at 37.5%). For
      both rigid and flexible rings, the ring A/T ratios and the sizer A/T ratios
      differed significantly (except for the 28-mm rigid ring and sizer). In comparison
      to the average human A/T ratio (36.6%), the ratio for most rings was
      significantly lower. CONCLUSIONS: The mismatch between rings and sizers results
      in three possible scenarios: the length of the anterior portion of the ring can
      be equal to, smaller than, or larger than the anterior portion of the sizer. The
      clinical implications are that the valve could become stenotic when the ring is
      implanted or that the anterior portion of the annulus could be altered (stretched
      or buckled). We feel that to assure improved long-term results, more accurate
      matching of sizers to rings is essential and that better matching to normal human
      anatomical ratios would be ideal.

PMID- 9635271
TI  - Tranexamic acid reduces bleeding after cardiopulmonary bypass when compared to
      epsilon aminocaproic acid and placebo.
AB  - Perioperative bleeding following coronary artery bypass grafting (CABG) is
      associated with increased blood product usage. Although aprotonin is effective in
      reducing perioperative blood loss, excessive cost prohibits routine utilization.
      Epsilon aminocaproic acid (EACA) and tranexamic acid (TA) are inexpensive
      antifibrinolytic agents, which, when given prophylactically, may reduce blood
      loss. The present study was undertaken to compare the efficacy of TA and EACA in
      reducing perioperative blood loss. METHODS: The study population consisted of
      first-time CABG patients. Patients were allocated in a prospective double-blind
      fashion: (1) group EACA (loading dose 15 mg/kg, continuous infusion 10 mg/kg per
      hour for 6 hours, N = 20); (2) group TA (loading dose 15 mg/kg, continuous
      infusion 1 mg/kg per hour for 6 hours, N = 20); (3) control group (infusion of
      normal saline for 6 hours, N = 19). RESULTS: Treatment groups were similar
      preoperatively. No significant difference in intraoperative blood loss or
      perioperative use of blood products was noted. D-dimer concentration was elevated
      in the control group compared to the EACA and TA groups (p < 0.05). Group TA had
      less postoperative blood loss than the EACA and control groups at 6 and 12 hours
      postoperatively (p < 0.05). TA had reduced total blood loss (600 +/- 49 mL)
      postoperatively compared to EACA (961 +/- 148 mL) and control (1060 +/- 127 mL, p
      < 0.05). CONCLUSION: TA and EACA effectively inhibited fibrinolytic activity
      intraoperatively and throughout the first 24 hours postoperatively. TA was more
      effective in reducing blood loss postoperatively following CABG. This suggests
      that TA may be beneficial as an effective and inexpensive antifibrinolytic in
      first-time CABG patients.

PMID- 9635272
TI  - Hypoplasia of the posterior leaflet as a rare cause of congenital mitral
      insufficiency.
AB  - A rare case of congenital mitral insufficiency characterized by the hypoplasia of
      the posterior leaflet is reported. At operation, the mitral valve was
      successfully repaired by a ring annuloplasty, which created a satisfactory
      surface of coaptation between the anterior leaflet and the bulky posterior
      muscular structure. The presence of this posterior muscular structure represents
      a developmental arrest at the stage of conversion from muscular chordae and
      leaflets to thin connective structures.

PMID- 9635273
TI  - Comparison of different regimens of electrical stimulation applied to
      nonmobilized and newly mobilized latissimus dorsi muscle.
AB  - We investigated the possibility of preventing further aggravation of muscle
      ischemia and necrosis in newly mobilized, unconditioned latissimus dorsi muscle
      (LDM) by utilizing short increments of stimulation with intervening rest periods.
      Adult St. Croix sheep (N = 12) weighing 30 +/- 8 kg were used in this study.
      Fatigue tests (30 min) using different stimulation regimens before and after LDM
      mobilization were performed on all animals; the length of time to return to
      baseline levels was also measured. Our investigation yielded results that
      contradict the conventional wisdom that any electrical stimulation damages newly
      mobilized LDM and will cause a considerable decrease in contractile force (CF).
      Stimulation regimens using continuous contractions at 30 and 60 contractions per
      minute (CPM) for 30 minutes were damaging to the LDM. CF also dropped
      significantly and returned slowly to baseline values: at 60 CPM, CF dropped to 50
      +/- 4% and did not return to baseline even after 90 minutes of rest; at 30 CPM,
      CF dropped to 61 +/- 4% and baseline was restored after 80 minutes of rest.
      Electrical stimulation using continuous contractions at a slower rate (15 CPM)
      was tolerable, although a 23% decrease in CF was noted (p < 0.05 when compared to
      60 CPM). These results did not satisfy us that such a regimen would be useful for
      cardiac assistance immediately after cardiomyoplasty. The work-rest regimen at 30
      CPM also gave poor results: CF decreased to 75 +/- 2% and baseline was restored
      after 80 minutes of rest. Promising results were seen when utilizing a work-rest
      regimen at 15 CPM. The newly mobilized LDM showed no visible signs of fatigue: CF
      decreased minimally to 92 +/- 3% (p < 0.05 when compared to 30 CPM), and light
      microscopic analysis of biopsies revealed no morphological damage exceeding that
      typically seen after subtotal mobilization. Such results open avenues for future
      investigations: beginning electrical stimulation immediately after
      cardiomyoplasty (using a single impulse and a slow rate of contraction);
      decreasing the length of time necessary to obtain full cardiac assistance; and
      beginning partial cardiac assistance immediately after cardiomyoplasty (if
      needed) for approximately 30 minutes several times a day.

PMID- 9635274
TI  - Hemodynamic response to in situ latissimus dorsi muscle stimulation: implications
      in dynamic cardiomyoplasty.
AB  - Dynamic cardiomyoplasty (DCM) involves the electrical stimulation of a pedicled
      latissimus dorsi muscle flap wrapped around the falling ventricle as a means of
      cardiac assist. To further elucidate a potential neurohumoral mechanism for
      improvement of cardiac output after myoplasty, we evaluated the hemodynamic
      effects of in situ stimulation of the latissimus dorsi muscle (in the absence of
      cardiomyoplasty). In seven mongrel dogs, a nerve cuff electrode (Medtronic 6901)
      was placed around the left thoracodorsal nerve (TDN). This was attached to a
      pulse generator (Medtronic, Itrel 7420), delivering a 4.0 volt, 0.19 second on,
      0.81 second off, 33 Hz, 210 microsecond pulse width, cyclic bursts similar to
      that used in DCM. Stroke volume index (SVI) and other hemodynamic parameters as
      well as plasma norepinephrine (NE) levels were measured at five stages: baseline,
      stimulator on at 0, 2, and 5 minutes, and stimulator off at 30 minutes after. The
      animals were then subjected to 4 weeks of rapid pacing at 240 beats/min
      (Medtronic 8329) to induce heart failure, and as the rapid pacing was
      discontinued, measurements were repeated as above. After rapid pacing, cardiac
      function was significantly depressed, and NE was elevated (133 +/- 69 versus 500
      +/- 353 pg/mL, p < 0.05). In the normal hearts, TDN stimulation increased SVI,
      heart rate, systemic pressure, and NE levels. In heart failure, however, no
      significant changes in cardiac function and NE levels were noted. In conclusion,
      our data indicate that in the normal hearts, afferent impulses from TDN
      stimulation alone may augment cardiac function by means of a neurohumoral effect
      that is not seen in severe heart failure. The implications of these findings in
      DCM are discussed.

PMID- 9635275
TI  - To know chalk from cheese.

PMID- 9635276
TI  - Myosin light chain phosphatase: subunit composition, interactions and regulation.
AB  - This review has presented some of the recent data on myosin phosphatase from
      smooth muscle. Although it is not conclusive, it is likely that most of the
      myosin phosphatase activity is represented by a holoenzyme composed of three
      subunits. These are: a catalytic subunit of 38 kDa of the type 1 phosphatase,
      probably the delta isoform (i.e. PP1c delta); a subunit of about 20 kDa whose
      function is not established; and a larger subunit that is thought to act as a
      target subunit. This is termed the myosin phosphatase target subunit, MYPT.
      Various isoforms of MYPT exist and the relatively minor distinctions are in the C
      terminal leucine zipper motifs and/or with inserts in the central region. Many
      regions of the molecule are highly conserved, including the ankyrin repeats in
      the N-terminal part of the molecule and the sequence around the phosphorylation
      site. In addition, these isoforms all contain the four residue PP1c-binding motif
      (Arg/Lys-Val/Ile-Xaa-Phe). MYPT has been detected in a variety of cells and thus
      is not unique to smooth muscle. With phosphorylated myosin as substrate, the
      phosphatase activity of PP1c is low and is enhanced on addition of MYPT. It is
      assumed that MYPT functions as a target subunit and binds to both PP1c and
      substrate. The N-terminal fragment of MYPT is responsible for the activation of
      PP1c activity, but how much of the N-terminal sequence is required is not
      established. An important point is that activation is not a general effect and is
      specific for myosin. It is not known if other substrates may be targeted to MYPT.
      There are two binding sites for PP1c on MYPT: a strong site in the N-terminal
      segment (containing the 4-residue motif) and a weaker site in the ankyrin
      repeats, possibly in repeats 5, 6 and 7. The location(s) of the myosin-binding
      sites on MYPT is controversial, and binding of myosin, or light chain, to both N-
      and C-terminal fragments has been reported. Regulation of myosin phosphatase
      activity involves changes in subunit interactions, although molecular mechanisms
      are not defined. There are basically two theories proposed for phosphatase
      inhibition (i.e. as seen in the agonist-induced increase in Ca2+ sensitivity).
      One hypothesis is that phosphorylation of Myosin light chain phosphatase MYPT (at
      residue 654 or 695 of the gizzard MYPT isoforms or an equivalent residue)
      inhibits the activity of the MP holoenzyme. The kinase involved is not
      established, but may be an unidentified endogenous kinase or a RhoA-activated
      kinase. The latter is an attractive possibility because there is convincing
      evidence that RhoA plays a crucial role in the Ca(2+)-sensitizing process in
      smooth muscle. A second idea involves arachidonic acid. This is released via
      phospholipase A2 and could either interact directly with MYPT and cause
      dissociation of the holoenzyme (thus effectively reducing the phosphatase
      activity to that of the isolated catalytic subunit), or it could activate a
      kinase that would phosphorylate MYPT and inhibit the phosphatase. It is possible
      that MP activity may also be activated, for example, following increases in cAMP
      and/or cGMP. Evidence in support of this is very limited and under in vivo
      conditions the phosphorylation of MYPT by the respective kinases has not been
      demonstrated. There is, however, a tentative hypothesis based on in vitro data
      that phosphorylation of MYPT by PKA alters its cellular localization. This
      involves a shuttle between the dephosphorylated membrane-bound and inhibited
      state (at least towards P-myosin) to a phosphorylated cytosolic or cytoskeletal,
      and active state. The pathway(s) discussed above originates at the cell membrane
      and is carried via one or more messengers to the level of the contractile
      apparatus where it is manifested by regulation of phosphatase activity. Various
      components of the route have been identified, including RhoA and the atypical PKC
      isoforms, but more remain to be discovered. It is possible that more than one
      pathway, or cascade, is

PMID- 9635277
TI  - Expression of lactate dehydrogenase, myosin heavy chain and myogenic regulatory
      factor genes in rabbit embryonic muscle cell cultures.
AB  - The expression of myogenic regulatory factors (MRFs), lactate dehydrogenase (LDH)
      and myosin heavy chains (MyHC), as markers of myogenesis, metabolism and
      contractility respectively, were investigated during differentiation of rabbit
      embryonic muscle cells in primary culture. Myf5, MyoD and myogenin mRNAs were
      abundantly expressed at day 1 of culture. The expression of Myf5 and MyoD mRNA
      transcripts decreased sharply as myoblasts fused and differentiated into
      myotubes, whilst myogenin mRNA was maintained throughout the duration of the
      culture. In contrast, MRF4 mRNA was weakly expressed on day 1 of culture, its
      expression increased slightly as myoblasts fused and reached a maximum level in 7
      day-old cultures containing striated myofibres. The specific activity of LDH
      increased linearly during myoblast proliferation and fusion. In 7-day-old
      cultures, LDH-M mRNA (dominant in glycolytic muscles) and LDH-H mRNA (predominant
      in perinatal and oxidative muscles) represented 38% and 62% of total LDH mRNA
      respectively. At this stage, immunocytochemical staining with perinatal and adult
      type MyHC antibodies showed that embryonic and perinatal MyHC isoforms were
      expressed in all myotubes, while few of them were stained by type I MyHC
      antibody. However, none of them expressed adult type II MyHC. The latter results
      were further supported by RT-PCR analysis of adult-type MyHC mRNA which showed
      that only the type I MyHC mRNA transcript was expressed. These data were in
      agreement with those reported in vivo on perinatal rabbit muscles. They differed
      from those obtained on cultured satellite cells isolated from adult rabbit fast
      twitch or slow-twitch muscles which did not express embryonic MyHC, and instead
      expressed fast- or slow-type MyHC according to their muscle origin. Taken
      together, these results further suggest that myogenic mononucleated cells express
      different properties in vitro according to their developmental origin as well as
      properties related to those of the muscles from which they were isolated.

PMID- 9635279
TI  - Improvement of the measurements on skinned muscle fibres by fixation of the fibre
      ends with glutaraldehyde.
AB  - Experiments with activated skinned muscle fibre segments are limited by the
      structural and mechanical instability of the preparations. The present study
      shows that fixation of the muscle fibre ends with glutaraldehyde significantly
      improves the reliability of such experiments. We tested the effects of a specific
      glutaraldehyde fixation technique on the structural stability and the mechanical
      properties of skinned rat and rabbit skeletal muscle fibres in an approach where
      the fibre segments are attached to the apparatus by gluing. Preparations with
      fixed and unfixed ends were compared. During the first few minutes of maximal
      activation, fibres with fixed and unfixed ends exhibited similar mechanical
      properties to one another, suggesting that our fixation procedure selectively
      impregnates the fibre ends without contaminating the remaining active fibre part.
      During prolonged maximal activations (3-60 min), preparations with fixed ends
      exhibited a better stability, both in the sarcomere length signal (detected by
      laser diffraction) and in the unloaded shortening velocity. Thus, our technique
      of muscle fibre end fixation caused a substantial improvement in the mechanical
      measurements on skinned muscle preparations.

PMID- 9635278
TI  - Effects of calcium and nucleotides on the structure of insect flight muscle thin
      filaments.
AB  - The structure of the insect flight muscle thin filament has been studied using a
      Drosophila mutant (Ifm(2)2) which does not contain thick filaments. Thin
      filaments that are biochemically identical to those of the wild type can be
      isolated free from thick filament contamination. We show that isolated thin
      filaments have different symmetries depending upon the calcium concentration.
      While the filaments mainly contain 13 subunits in six turns of the 5.9 nm genetic
      helix in the absence of calcium, 50% of the filaments have 28 subunits in 13
      turns of the genetic helix at calcium concentrations equivalent to those present
      during muscle contraction. We also show that the structure (mainly the helical
      order) of the thin filaments depends on the nature of the nucleotide bound to the
      actin monomers. Three-dimensional reconstructions of the thin filaments in the
      presence and absence of calcium show that tropomyosin moves between two different
      positions on the actin filament. However, in Drosophila the amplitude of the
      movement as well as the disorder in the positions of the components (tropomyosin,
      troponin complex) are larger than those generally observed in other species.

PMID- 9635280
TI  - Acute and sustained effects of isometric and lengthening muscle contractions on
      high-energy phosphates and glycogen metabolism in rat tibialis anterior muscle.
AB  - Previous studies have shown that lengthening contractions, in contrast to
      isometric contractions, readily result in sustained malfunctioning of the
      exercised muscles. The present study was performed to investigate whether an
      exercise period with many (240) lengthening contractions (LC) results in
      alterations in muscle high-energy phosphates and inosine monophosphate (IMP)
      content, different from muscles performing a few (60) lengthening or a few (60)
      or many (240) isometric contractions (IC). Moreover, we sought for a possible
      cause(s) of the inability to replenish muscle glycogen stores following LC. Rat
      tibialis anterior muscles were subjected in vivo to either 60 or 240 LC or IC.
      Structural muscle damage occurred only after 240 LC. The fact that tissue
      glycogen levels declined to a similar extent during LC and IC suggests that the
      energy demand was comparable during both types of exercise. Nevertheless, the
      observation that on the one hand tissue stores of adenine nucleotides showed a
      greater decline, and on the other hand the tissue content of IMP increased to a
      significantly higher level after LC than after IC, clearly indicates that muscle
      energy metabolism is more disturbed during LC than during IC. The high tissue
      levels of IMP may contribute to impaired mechanical function as previously
      observed in muscles subjected to LC. In contrast to 240 IC, 24 hours after 240
      LC, tissue glycogen stores and high-energy phosphate levels were not restored to
      control values. The present findings indicate that depressed glycogen synthase
      activity and impaired activity of the mitochondrial marker enzyme cytochrome C
      oxidase probably contribute to a continuous disturbance of energy metabolism in
      the exercised muscles during the 24 hours following 240 LC.

PMID- 9635281
TI  - Probing the coupling of Ca2+ and rigor activation of rabbit psoas myofibrillar
      ATPase with ethylene glycol.
AB  - We have exploited solvent perturbation to probe the coupling of Ca2+ and rigor
      activation of the ATPase of myofibrils from rabbit psoas. Three techniques were
      used: overall myofibrillar ATPases by the rapid-flow quench method; kinetics of
      the interaction of ATP with myofibrils by fluorescence stopped-flow; and
      myofibrillar shortening by optical microscopy. Because of its extensive use with
      muscle systems, ranging from myosin subfragment-1 to muscle fibres, we chose 40%
      ethylene glycol as the relaxing agent. At 4 degrees C, the glycol had little
      effect on the myofibrillar ATPase at low [Ca2+], but at high [Ca2+] the activity
      was reduced 50-fold, close to the level found under relaxing conditions, and
      there was no shortening. However, the ATPase of chemically cross-linked
      myofibrils (permanently activated even without Ca2+) was reduced only 3-4-fold.
      The lesser reduction of the ATPase of permanently activated myofibrils was also
      observed in single turnover experiments in which activation occurs by a few heads
      in the rigor state activating the remaining heads. The addition of ADP, which
      also promotes strong head-thin filament interactions, also activated the ATPase
      but only in the presence of Ca2+. Further experiments revealed that in 40%
      ethylene glycol, Ca2+ does initiate shortening but only with the aid of strong
      interactions and at temperatures above 15 degrees C. This confirms that in the
      organized and intact myofibril, Ca2+ and rigor activation are coupled, as
      proposed previously for regulated actomyosin subfragment-1.

PMID- 9635283
TI  - Involvement of the cytoskeleton in calcium-dependent stress relaxation of rat
      aortic smooth muscle.
AB  - Rat aortic smooth muscle exhibits a remarkable capacity for stress relaxation,
      the release of tension following tissue stretch. Stress relaxation was markedly
      enhanced in contracted aortic rings compared with unstimulated tissue. The
      magnitude of stress relaxation in contracted aortic rings correlated well with
      the passive tension imposed on the tissue by stretching, but showed little
      relationship to changes in tissue length or to the level of tension developed in
      response to agonist stimulation prior to stretch. The enhancement of stress
      relaxation in precontracted tissue was not affected by intimal rubbing or
      treatment with L-NAME. By comparison, the removal of extracellular calcium
      markedly attenuated stress relaxation. In addition, the use of cytochalasin B to
      block actin polymerization inhibited stress relaxation, whereas colchicine, a
      drug used to cause microtubule disassembly, had no effect on the phenomenon. The
      results indicate that the enhanced stress relaxation in contracted tissue is a
      calcium-dependent process and is not due to passive tissue elastic properties. We
      suggest that stress relaxation may not involve cross-bridge formation but could
      be explained by the remodelling of a portion of the tension-bearing actin
      cytoskeleton.

PMID- 9635282
TI  - Troponin-T is a calcium-binding protein in insect muscle: in vivo
      phosphorylation, muscle-specific isoforms and developmental profile in Drosophila
      melanogaster.
AB  - Two sets of muscle polypeptides showing calcium-binding capacity and intense
      labelling in vivo with 32P were purified and characterized from Drosophila
      melanogaster adult extracts. The polypeptides exhibit crossed immunoreactivity
      and share similar biochemical properties such as those involved in purification.
      They have been identified as isoforms of troponin-T (TnT) by sequence analysis of
      a cDNA clone isolated from an embryonic library. The two sets of TnT polypeptides
      correspond to the fibrillar and non-fibrillar muscle isoforms, respectively. The
      non-fibrillar muscle isoforms separate into two bands which are differentially
      expressed during development. Analysis of TnT isoforms in bee thoraces indicates
      that the expression of the fibrillar muscle isoform correlates with the
      acquisition of functional flight capability. In vivo labelling experiments reveal
      that the two TnT sets are readily phosphorylated. The Drosophila TnTs show
      calcium-binding properties by three different types of assays. Our results
      suggest that this property could be specific to insect TnTs and may be related to
      the long, extremely acidic polyglutamic carboxy-terminus present in these
      polypeptides, which does not occur in non-arthropod TnTs.

PMID- 9635284
TI  - Mechanical alterations in smooth muscle from mice lacking desmin.
AB  - Mice with a null mutation introduced in the desmin gene were used to study the
      mechanical role of intermediate filaments in smooth muscle cells. Vas deferens
      (VD), urinary bladder (UB) and portal vein (PV) preparations were obtained from
      adult animals lacking desmin (Des -/-) and from age- and weight-matched wild-type
      animals (Des +/+). Active force per cross-sectional area was decreased in the
      smooth muscle of the Des -/- compared with Des +/+ mice (VD to 42%; UB to 34%).
      Quantitative gel electrophoresis suggests a marginally lower cellular content of
      myosin, but the organization of the contractile apparatus appeared unchanged by
      electron microscopy. A similar reduction in stress was measured in Des -/-
      skinned fibres showing that altered activation mechanisms were not involved. The
      results indicate that the reduced active force is caused by low intrinsic force
      generation of the contractile filaments or subtle modifications in the coupling
      between the contractile elements and the cytoskeleton. The relationship between
      length and passive stress was less steep in the Des -/- samples and a second
      length force curve after maximal extension revealed a loss of passive stress. The
      maximal shortening velocity was reduced in Des -/- skinned VD and UB preparations
      by approximately 25-40%. This was associated with an increased relative content
      of the basic essential myosin light chain, suggesting that alterations in the
      contractile system towards a slower, more economical muscle had occurred. PV
      preparations showed no difference in mechanical properties in Des +/+ and Des -/-
      animals, a result that was consistent with the predominance of vimentin instead
      of desmin in this vascular tissue. In conclusion, the results show that, although
      intermediate filaments in smooth muscle are not required for force generation or
      maintenance of passive tension, they have a role in cellular transmission of both
      active and passive force.

PMID- 9635285
TI  - Evidence for distinct fast and slow myogenic cell lineages in human foetal
      skeletal muscle.
AB  - To analyse the myogenic cell lineages in human foetal skeletal muscle, muscle
      cell cultures were prepared from different foetal stages of development. The in
      vitro muscle cell phenotype was defined by staining the myotubes with antibodies
      to fast and slow skeletal muscle type myosin heavy chains using immunoperoxidase
      or double immunofluorescence procedures. The antibodies to fast skeletal muscle
      myosin heavy chains stained nearly all myotubes dark in cell cultures prepared
      from quadriceps muscles at 10-18 weeks of gestation. The antibodies to slow
      skeletal muscle myosin heavy chains, in contrast, stained only 10-40% of the
      myotubes very dark. The remaining myotubes were further subdivided into two
      populations, one of which was unstained while the other stained with variable
      intensity for slow myosin heavy chain. The slow myosin heavy chain staining was
      not influenced by the nature of the substratum used to culture these cells,
      although the growth of muscle cell cultures was greatly improved on matrigel
      coated dishes. The presence of both slow and fast myosin heavy chains was
      detected even when myotubes were grown on uncoated petri dishes. The myotube
      diversity was further investigated by analysing the clonal populations of human
      foetal skeletal muscle cells in vitro. When cultured at clonal densities, two
      types of myogenic clones were identified by their differential staining with
      antibodies to slow myosin heavy chain. As was the case with the high density
      muscle cell cultures, virtually all myotubes in both groups of clones stained
      with antibodies to fast myosin heavy chains. Antibodies to slow myosin heavy
      chains stained nearly all myotubes dark in one group of myogenic clones, but only
      a subset of the myotubes stained dark for slow myosin heavy chain in the second
      group of clones. The proportion of slow myosin heavy chain positive myotubes in
      this group varied in different clones. The myogenic diversity was thus apparent
      in both high density and clonal human muscle cell cultures, and myogenic cells
      retained their ability to modify their muscle cell phenotype.

PMID- 9635286
TI  - The annual meeting on muscle contraction and cell motility. Tokyo, Japan, 6-8
      January 1998.

PMID- 9635287
TI  - Missing children found dead.
AB  - Forensic evidence in child homicide cases is critical to determine sexual abuse.
      Forensic evidence can help focus an investigation on a suspect through DNA
      results. Of 210 missing children found deceased, 68% were homicides, 16% had
      accidental causes, 12% were unknown, and 4% were suicides.

PMID- 9635288
TI  - Forbidden love: sexual exploitation in the forensic milieu.
AB  - Strategies must be developed within forensic psychiatric nursing practice that
      deal with issues surrounding forbidden love before, during, and after they arise.
      Unfortunately, nurses are generally ill prepared to deal with the sexual dilemmas
      that can occur in clinical practice. Sexual dilemmas must be recognized as an
      occupational hazard and not a professional taboo. Open acknowledgement that the
      potential for abuse exists in all nurse-client relationships is the key to
      avoiding the pitfalls that lead to sexual impropriety.

PMID- 9635289
TI  - "How do you feel?" Self-reported health as an indicator of current physical and
      mental health status.
AB  - Self-reported health can serve as a reliable indicator of an individual's
      physical health status and future morbidity and mortality. Although patients are
      commonly asked "How do you feel?" they are rarely asked to rate their health on a
      continuum of excellent to poor. This question can be helpful in ascertaining the
      need for further assessment or referral.

PMID- 9635290
TI  - Process-oriented critical pathways in inpatient psychiatry: our first year.
AB  - The critical pathway methodology of assigning and timing staff interventions and
      expected patient outcomes has developed worldwide recognition, but is less likely
      to be used in psychiatry than in other medical fields. At St. Mary's in
      Rochester, New York, an interdisciplinary team adapted the critical pathway
      concept to meet the needs of an acute inpatient population with relative success.
      Although staff education needs continue and plans to modify the pathway are in
      progress, all staff feel that the critical pathway is a viable tool for enhancing
      patient care and optimizing resources use. Benefits, obstacles, and suggestions
      are discussed.

PMID- 9635291
TI  - Caring in a managed care environment--a case study in teamwork.
AB  - Level of care decisions in managed care require matching the patient's intensity
      of symptoms with the appropriate placement in the least restrictive setting. In
      planning appropriate treatment for a patient, the case manager at a managed care
      organization (MCO) considers "Why now?," examining the patient's diagnosis, as
      well as other pertinent factors, such as precipitant and the proximal cause for
      the patient's request for help. Team efforts between the MCO clinicians and the
      patient's treating clinicians improve the likelihood of patient/treatment
      outcome.

PMID- 9635292
TI  - Regulation of growth hormone receptor gene expression.
AB  - Pituitary growth hormone (GH) is essential for postnatal growth in animals. GH
      exerts its actions by direct effect on target organs and by stimulating the
      production of insulin-like growth factor I (IGF-I). At the tissue level, the
      pleiotropic actions of GH result from the interaction of GH with a specific cell
      surface receptor, the GH receptor (GHR). The GHR belongs to the hematopoietic
      receptor superfamily. The human GHR is the product of a single gene located on
      chromosome 5p13.1-p12 and spans at least 87 kb. Transcripts from this gene are
      characterized by the presence of disparate 5' untranslated exons. In the liver at
      least eight different GHR 5' untranslated regions (UTRs) have been described.
      This heterogeneity in the 5' UTR most likely results from the splicing of the
      various exon 1 fragments to a common splice site located 11 bp upstream of the
      initiating ATG. Heterogeneity in the 5' UTR sequences of the GHR transcripts
      indicates that transcriptional control of the locus is complex. GHR gene
      expression is minimal to absent in the fetus, with the postnatal increase in
      expression in the liver being maximal during pregnancy. GHR gene expression is
      also regulated by factors such as nutritional intake, GH, steroid hormones, and
      diabetes mellitus. Available information about the molecular mechanisms
      regulating expression of the GHR gene is discussed. Thus the GHR gene presents a
      picture of multiple 5' untranslated exons under the control of multiple
      promoters. The use of alternate promoters for initiation of transcription in
      conjunction with differential splicing allows for exquisite regulation of gene
      expression. This schema is appropriate for a protein that is essential to many of
      the physiological processes that are crucial for the survival and well-being of
      the organism.

PMID- 9635293
TI  - Molecular analysis and prenatal diagnosis of human fumarase deficiency.
AB  - Fumarase deficiency is a rare autosomal recessive disorder of the citric acid
      cycle causing severe neurological impairment. The cDNA for both the rat and human
      enzymes has been cloned previously and shown to encode a coding region of 1.46
      kb. To scan for mutations in fumarase-deficient patients we amplified the coding
      region of fumarase from fibroblast/lymphoblast cDNA employing the oligonucleotide
      primers designed from the published human and rat cDNA sequence. We then directly
      sequenced the polymerase chain reaction product. In seven unrelated patients, we
      detected four missense mutations (A265T, D383V, F269C, K187R), a nonsense
      mutation (W458X), a 3-bp AAA insertion that introduces an additional lysine
      residue at codon 435, and a spontaneous new mutation resulting in a 74-bp
      deletion (66del74). Seven at-risk pregnancies were monitored with one prenatal
      diagnosis of fumarase deficiency by molecular analysis and favorable outcome of
      the other pregnancies as predicted by enzyme assay of cultured fetal cells or
      molecular analysis.

PMID- 9635294
TI  - Molecular and biochemical basis of galactosemia.
AB  - Galactosemia is a clinically heterogeneous autosomal recessive inborn error of
      metabolism caused by deficiency of galactose-1-phosphate uridylyltransferase
      (GALT). Despite the numerous point mutations identified in the GALT gene, the
      prevalence of these mutations in different ethnic groups has not been studied.
      Reports on genotype/phenotype correlation are not consistent due to the small
      sample sizes studied and the lack of a sensitive enzyme assay. We applied
      multiplex PCR/ASO dot blot analysis to screen 293 galactosemic patients for 17
      known point mutations in exons 5, 6, and 10. Our data demonstrate that only 7 of
      these mutations were detected in our patients, accounting for 65% of the GALT
      mutant alleles. Although Q188R is the most common mutation in Caucasian and
      Hispanic patients, the S135L mutation is most common in African-Americans.
      Another mutation, F171S, was observed only among African-American patients. An
      improved, sensitive, and accurate method was used to measure GALT activity in
      patient's red blood cells. The results indicated that patients homozygous for
      Q188R have no enzyme activity while those homozygous for S135L had residual
      enzyme activity. Interestingly, both Q188R/S135L and S135L/F171S compound
      heterozygotes demonstrated zero enzyme activity. Overall, 85% of Q188R compound
      heterozygotes also did not have any enzyme activity, whereas the remaining Q188R
      and the majority of S135L compound heterozygotes expressed variable amounts of
      GALT activity. We speculate that heterodimeric subunit interaction plays an
      important role in determining the overall enzymatic activity. Various genotypes
      thus result in biochemical and clinical heterogeneity among the patients.

PMID- 9635295
TI  - Alpha 1-antitrypsin nonsense mutation associated with a retained truncated
      protein and reduced mRNA.
AB  - alpha 1-Antitrypsin (alpha 1AT) provides the major protection in the lung against
      neutrophil elastase-mediated proteolysis. Inheritance of alpha 1AT deficiency
      alleles is associated with an increased risk of emphysema and liver disease.
      alpha 1AT null alleles cause the total absence of serum alpha 1AT and represent
      the ultimate in a continuum of alleles associated with alpha 1AT deficiency. The
      molecular mechanisms responsible for absence of serum alpha 1AT include splicing
      abnormalities, deletion of alpha 1AT coding exons, and premature stop codons. We
      identified an Italian individual with asthma, emphysema, and a very low level of
      serum alpha 1AT. DNA sequencing demonstrated the Mprocida deficiency allele and a
      novel null allele, QOtrastevere (c654 G-->A, W194Z), a nonsense mutation near the
      intron 2 (IVS2) splice acceptor site. To determine the molecular basis of
      QOtrastevere and specifically to evaluate whether this nonsense mutation
      interfered with mRNA processing by altered splicing, we used a Chinese hamster
      ovary cell line permanently transfected with QOtrastevere or normal M alpha 1AT
      with and without IVS2. Northern blot analysis demonstrated that the normal M
      construct, with or without IVS2, expressed alpha 1AT mRNA of a similar size. The
      nonsense mutation was associated with moderately reduced alpha 1AT mRNA
      regardless of the presence or absence of IVS2. Reduction in alpha 1AT mRNA
      regardless of the opportunity for splicing supports a translational-translocation
      model as the cause of reduced alpha 1AT mRNA rather than the nuclear scanning
      model. Pulse-chase studies followed by immunoprecipitation demonstrated an
      endoplasmic reticulum-retained 31 kDa QOtrastevere alpha 1AT, which was rapidly
      degraded. Although mRNA content was moderately reduced, retention and rapid
      intracellular degradation of the truncated form are the major mechanisms for the
      absence of secreted alpha 1AT.

PMID- 9635296
TI  - Type 2 Gaucher disease with hydrops fetalis in an Ashkenazi Jewish family
      resulting from a novel recombinant allele and a rare splice junction mutation in
      the glucocerebrosidase locus.
AB  - Gaucher disease, the deficiency of the lysosomal enzyme glucocerebrosidase (EC
      3.2.1.45), is frequently encountered in the Ashkenazi Jewish population. Carrier
      screening for Gaucher disease by enzyme analysis performed during a routine
      pregnancy indicated that both Ashkenazi parents were carriers. Screening for four
      common Gaucher mutations was subsequently performed on fetal and parental DNA.
      None of the common Ashkenazi mutations were identified. However, when exons 9-11
      were amplified and digested with NciI to detect the L444P mutation, it appeared
      that the mother and the fetus had an unusual allele and that the expected
      paternal allele was not present. When the fetal amniocytes were found to have
      less than 2% of the normal glucocerebrosidase activity and a fetal sonogram
      revealed hydrops fetalis, the pregnancy was terminated. The diagnosis of severe
      type 2 Gaucher disease was confirmed at autopsy. Ultrastructural studies of
      epidermis from the fetus revealed the characteristic disruption of lamellar
      bilayers, diagnostic for type 2 Gaucher disease. In subsequent studies of the
      fetal DNA, long-template polymerase chain reaction amplification revealed one
      appropriately sized band (approximately 6.5 kb) and one smaller (approximately
      5.2 kb) band. Sequencing of the approximately 5.2-kb fragment identified a novel
      fusion allele resulting from recombination between the glucocerebrosidase gene
      and its pseudogene beginning in intron 3. This fusion allele was inherited from
      the father. The result was confirmed by Southern blot analysis using the enzyme
      S8tII. Sequencing of the 6.5-kb fragment identified a previously described,
      although rare, T-to-G splice junction mutation in intron 10 of the maternal
      allele, which introduced an NciI site. The couple had a subsequent pregnancy
      which was also found to be affected. This case study identifies a novel
      recombinant allele and an unusual splice junction mutation, and demonstrates that
      even in the Ashkenazi population, screening for common mutations may not
      accurately identify the most severe forms of the disease.

PMID- 9635297
TI  - Aminopeptidase N in sera of healthy subjects is a different N-terminal processed
      derivative from the one obtained from maternal serum.
AB  - A major aminopeptidase present in normal human serum was purified to homogeneity
      as a 150-kDa molecular species. Western blotting confirmed the binding of an anti
      aminopeptidase N antibody to the protein. The N-terminal amino acid sequence of
      the enzyme was determined. The first 13 amino acids of the enzyme completely
      matched amino acids 59-71 of the sequence predicted from the human intestinal
      aminopeptidase N cDNA nucleotide sequence. As reported previously, aminopeptidase
      N from maternal serum had 68 fewer amino acid residues at the N-terminus than the
      enzyme obtained from detergent-solubilized membranes. The results indicate that
      aminopeptidase N in normal serum is a different N-terminal processed derivative
      from that obtained from maternal serum.

PMID- 9635298
TI  - Identification of urokinase as a hyperoxia-inducible gene.
AB  - Hyperoxia has deleterious effects on lung form and function; however, the
      molecular events initiated by oxygen exposure remain unclear. We hypothesized
      that macrophages function as important intermediaries in the protective response
      of lung tissues after exposure to hyperoxia. This hypothesis was tested by
      exposing cultured macrophages (RAW 264.7 cells) to hyperoxia for 24 h and then
      applying the conditioned medium from these cells to cultured pulmonary epithelial
      cells or to pulmonary microvascular endothelial cells. We observed that the
      expression of manganese superoxide dismutase mRNA increased in both target cell
      lines. Therefore, we next hypothesized that exposure of these macrophages to
      hyperoxia results in a change in gene expression which could be detected by
      differential display PCR (ddPCR). This hypothesis was tested by exposing RAW
      264.7 cells to > or = 95% oxygen (or normoxia) for 24 h, harvesting RNA, and
      performing ddPCR. A cDNA fragment upregulated by hyperoxia was identified and
      reamplified. Verification of differential expression of mRNA was done by Northern
      analysis. A mRNA which was reproducibly upregulated by hyperoxia, as well as by
      lipopolysaccharide and interferon gamma, was identified. The differentially
      expressed PCR product was cloned and sequenced, revealing a product with 99%
      identity to mouse urokinase mRNA. We speculate that one function of pulmonary
      macrophages following a hyperoxic exposure is to secrete urokinase.

PMID- 9635299
TI  - [Neurosurgery and molecular biology: (series 4) molecular biology of
      oncogenesis].

PMID- 9635300
TI  - [Temporary arterial occlusion in aneurysm surgery].

PMID- 9635301
TI  - [Visualization of venous system by volumegraph: navigation system of brain tumor
      surgery].

PMID- 9635302
TI  - [Differential diagnosis of hyponatremia following subarachnoid hemorrhage].
AB  - Hyponatremia is a common complication after subarachnoid hemorrhage (SAH).
      Although the mechanism of hyponatremia is still controversial, cerebral salt
      wasting syndrome (CSNS) is currently regarded as being more responsible than the
      syndrome of inappropriate secretion of antidiuretic hormone (SIADH). The aim of
      our study was to assess the plasma volume status of a patient with hyponatremia
      following subarachnoid hemorrhage. In doing this it may be possible to indirectly
      differentiate its pathogenesis. Fifty patients with SAH were studied. Twenty
      patients demonstrated hyponatremia (serum sodium < 135 mEq/L) during day 7 to 13
      after subarachnoid hemorrhage. Patients with hyponatremia were categorized on the
      basis of their daily body weight, and central venous pressure. Group A consisted
      of patients with hypovolemia (16 patients), with the onset time of hyponatremia
      being day 7 to 9. Group B included those with hypervolemia (4 patients);
      hyponatremia was observed during day 10 to 11 and was corrected in all patients
      within 72 hours after induction of fluid restriction. Our findings suggest that
      hyponatremia following subarachnoid hemorrhage usually occurs due to CSWS,
      although SIADH remains as a minor pathogenesis. We conclude that the combination
      of daily body weight and CVP measurements is a simple and practical method to
      distinguish promptly SIADH from CSWS.

PMID- 9635303
TI  - [Japan Coma Scale as a grading scale of subarachnoid hemorrhage: a way to
      determine the scale].
AB  - BACKGROUND: The grading scale for subarachnoid hemorrhage (SAH) with inter-grade
      outcome differences is essential for evaluating the effectiveness of newly
      developed therapeutic modalities. Although Hunt's grade and WFNS scale have been
      widely used, these grading scales do not meet this requirement. We previously
      proposed a revised WFNS scale based solely on the Glasgow Coma Scale (GCS) that
      has intergrade outcome differences of high-level significance. The Japan Coma
      Scale (JCS) has been long and widely used in Japan. The purpose of this study is
      to show whether it is possible to determine a reasonable SAH grading scale based
      on the JCS and to show a way to determine an SAH grading scale. PATIENTS AND
      METHODS: We retrospectively analyzed 1398 consecutive cases of aneurysmal SAH
      operated on within Day 7 of the latest onset. The preoperative JCS and GCS were
      evaluated just before the surgery and the Glasgow Outcome Scale (GOS), analyzed
      with numerical transformation (1 = dead to 5 = good recovery), was estimated at 6
      months after the onset. All 510 possible combinations of scores of JCS were
      statistically tested under the following 2 assumptions; (1) JCS = 0 and JCS = 100
      fall into a single independent grade. (2) No other single JCS score should fall
      into a single grade. RESULTS: The outcome differences between JCS 0 and 1, and
      100 and 200 are significant. The outcome difference between JCS 30 and 100 is
      relatively higher than any other set of 2 scores of JCS. Only 5 combinations are
      practical among the candidates to be analyzed. Out of 510 combinations, the
      following combination shows the highest inter-grade outcome differences; I (JCS =
      0, n = 375, mean GOS = 4.78) II (JCS = 1, 2; n = 310; mean GOS = 4.47) III (JCS =
      3-30; n = 476; mean GOS = 3.96) IV (JCS = 100; n = 96; mean GOS = 3.10) V (JCS =
      200, 300; n = 141; mean GOS = 2.33). In JCS, the mean outcome of JCS = 3 is worse
      than those of JCS = 10, 20, and 30. The outcome difference between JCS 0 and 1 is
      only significant in patients over 60 years old. CONCLUSION: Taking all the 510
      possible combinations of JCS into consideration, we obtained a reasonable
      combination containing 5 grades. Although this grading scale showed good inter
      grade outcome differences, JCS is not preferable to GCS as a consciousness
      evaluation system in the acute phase of SAH. We emphasize the importance of this
      way to determine a grading scale with a combinatorial approach, which can be
      applicable for re-evaluating the grading scales in the future.

PMID- 9635304
TI  - [Discrepancy between surgeon's binocular parallax perception and manipulation in
      the neurosurgical operation].
AB  - The application of virtual reality (VR) to the neurosurgical field has been
      increasing recently, however, the relation between the surgeon and the VR
      environment is rarely studied. We examined the trajectory of a surgical
      instrument during manipulation of a virtual object using a video-see-through
      microscope and a neurosurgical navigator (CANS Navigator) to find better surgeon
      microscope interface. A resin cylindrical phantom was produced representing the
      surgical field, which included two 3 dimensionally arranged small spheres and a
      virtual 'gate'. The phantom was fixed and set under the microscope with a skull
      clamp mimicking conditions in an ordinary craniotomy. Firstly, the binocular
      parallax perception under microscope was examined. Experienced and inexperienced
      neurosurgeons were asked to learn the position of the virtual 'gate' for 3
      minutes. Then, after 5 minutes to point with the navigator probe (suction tube),
      under various conditions; under the naked eyes, under the microscope, under the
      navigator without observing the phantom, and under the microscope with picture in
      picture (PIP) display of the navigational image. The positions of the suction
      tube were recorded at real time into the navigator for later analysis. Secondly,
      the task performance in this VR environment was studied by analyzing the
      trajectory of the suction tube from one sphere to the other sphere passing the
      virtual 'gate' under various conditions. A significant difference in pointing
      precision between experienced and inexperienced neurosurgeons was able to be
      observed only under microscope. This difference was mainly derived from
      overestimation of the depth of the virtual 'gate' by the inexperienced
      neurosurgeons. Among the above conditions, pointing under the microscope with PIP
      was able to be performed the most precisely and the most promptly. This study
      disclosed the presence of stereoscopic distortion in the microscope. The PIP
      display of the navigational image in the microscopic view remarkably improved the
      task performance, which could be accounted for by the correction of the somewhat
      distorted binocular parallax perception under the neurosurgical microscope by the
      provision of another visual key.

PMID- 9635305
TI  - [A case of bilateral infraoptic course of ACA associated with multiple cerebral
      artery aneurysms].
AB  - Infraoptic course of anterior cerebral artery (ACA) is a rare cerebral vascular
      anomaly frequently associated with intracranial aneurysm. A 58-year-old woman
      suffered, subarachnoid hemorrhage due to aneurysmal rupture. Carotid angiography
      revealed multiple aneurysms and bilateral infraoptic course of ACA. Usual A1
      segments were not visualized on both sides. These findings were also confirmed by
      craniotomy. Only 46 cases have been reported including ours. In this paper, we
      reviewed previously reported cases and the cause of aneurysm formation was
      discussed.

PMID- 9635306
TI  - [Usefulness of positron emission tomography to STA-MCA anastomosis for the case
      with cerebral infarction].
AB  - The ischemic area surrounding the cerebral infarction in the eloquent area was
      salvaged by STA-MCA bypass surgery. Both the misery perfusion area evaluated by
      positron emission tomography (PET) using the [15O] gas inhalation steady-state
      method and clinical symptoms improved within a year after surgery. To confirm the
      ischemic area and select the suitable recipient artery was important for
      successful bypass surgery, because only an artery covering the ischemic area is
      expected to have low resistance. In this case a large ischemic area with
      disturbed, vasodilatation by Diamox was detected on the SPECT. However, PET
      clearly exposed the localized misery perfusion area in the overestimated ischemic
      area by SPECT. We describe our experience and discuss the technique and efficacy
      of PET for STA-MCA anastomosis surgery.

PMID- 9635307
TI  - [A new operative technique of posttraumatic syringomyelia: thecoperitoneal
      shunt].
AB  - The authors report a successful case of operative treatment for a patient with a
      traumatic syringomyelia. A 33-year-old male presented with arm pain and right
      sided sensory loss due to posttraumatic syringomyelia. Magnetic resonance image
      showed syringomyelia from the upper cervical cord to the lower thoracic cord.
      Based on the hypothesis of Ball and Dayan, and Williams, a thecoperitoneal shunt
      operation was performed. The proximal shunt catheter was placed in the
      subarachnoid space rostral to the injury level and the distal shunt catheter was
      introduced percutaneously into the peritoneum. Postoperative radiological studies
      showed improvement and progressive clinical deterioration stopped. The advantages
      of this surgery are that it is less invasive to the spinal cord, and that there
      is a lower shunt malfunction rate because of the use of a D-L catheter which
      develops less shunt obstruction. Furthermore, we were able to evaluate shunt flow
      from the valve. In spite of multicystic syrinx, we were easily able to determine
      the placement of the shunt catheter for this operation. For these reasons, the
      thecoperitoneal shunt can be placed before further expansion of the syrinx. We
      think that this method is safer for patients with incomplete cord injury than S-P
      shunt or S-S shunt.

PMID- 9635308
TI  - Prevention of bacterial endocarditis: a statement [of confusion] for the
      [pediatric] dental professional.

PMID- 9635309
TI  - Treating Medicaid children.

PMID- 9635310
TI  - Detection of fungal organisms in saliva from HIV-infected children: a preliminary
      cytologic analysis.
AB  - PURPOSE: Fungal infections in HIV-infected individuals are associated with
      advancement of disease. In pediatric HIV infection, symptomatic children have a
      significantly higher incidence of clinical candidiasis and persistent drug
      resistant candidiasis than do asymptomatic HIV-infected children. The purpose of
      this preliminary cytologic study was to determine the prevalence of fungal
      organisms in whole unstimulated saliva from children with vertically acquired HIV
      infection. METHODS: The subjects included 27 HIV-infected and 11 HIV-exposed, but
      uninfected, children. Whole unstimulated saliva was obtained for cytologic
      evaluation (hematoxylin and eosin, silver stains) with selected samples evaluated
      by electron microscopy. RESULTS: Yeast and hyphae were identified cytologically
      in 19% of HIV-infected (22% symptomatic HIV-infected, 11% asymptomatic HIV
      infected) and 9% of HIV-exposed, but uninfected, children. Fungal organisms were
      found more frequently in HIV-infected with moderate (18%) and severe (27%)
      suppression. Fungi were more frequent with antiretroviral therapy (22%) vs no
      antiretroviral therapy (0%) and no antifungal therapy (20%) vs. antifungal
      therapy (7%). Yeast and hyphal fungal forms are more prevalent in symptomatic HIV
      infection with moderate and severe suppression, and those receiving
      antiretroviral agents, but no antifungal medications. CONCLUSION: Fungal
      organisms in the saliva may reflect oral carriage or mucosal colonization, which
      may influence the development of clinically significant candidiasis in these
      immunocompromised children.

PMID- 9635311
TI  - Gingival status of HIV+ children and the correlation with caries incidence and
      immunologic profile.
AB  - PURPOSE: The aim of this study was to determine gingival health and caries levels
      in HIV-infected children. METHODS: The modified gingival index (GI) of 43 HIV+
      children of both sexes, aged between 2 and 12 years, was measured and correlated
      with the DMFT/dmf. The children's immunodeficiency level was also established by
      means of the CD4:CD8 ratio. Pearson's product-moment correlation co-efficient and
      the Mann-Whitney U test were used. RESULTS: The GI was significantly related to
      the DMFT/dmf. The children with a GI = 0 presented significantly more DMFT/dmf
      than the children with a GI > or = 0.1, but there were no significant differences
      between the GIs of caries-free children and those with DMFT/dmf > or = 1. The
      children who presented a CD4:CD8 > or = 0.5 ratio presented less DMFT/dmf
      compared with children who presented a CD4:CD8 < 0.5 ratio. The children who
      presented a CD4:CD8 < 0.5 ratio presented a statistically significant correlation
      between their GI and their DMFT/dmf, unlike children who presented a CD4:CD8 > or
      = 0.5 ratio. Children with a CD4:CD8 < 0.5 who showed a greater DMFT/dmf index
      also showed greater gingival inflammation. CONCLUSIONS: In this study, children
      with greater caries experience showed more gingival inflammation. In addition, a
      greater immunological deficiency might indicate a greater caries experience in
      children.

PMID- 9635312
TI  - Microleakage of sealants after conventional, bur, and air-abrasion preparation of
      pits and fissures.
AB  - PURPOSE: The aim of this study was to compare the microleakage of unfilled and
      filled sealants after conventional, bur, and air-abrasion tooth preparation.
      METHODS: Seventy-two extracted molars were randomly divided into three groups. In
      group 1, 24 teeth were prepared by pumicing and acid etching with 37% phosphoric
      acid. In group 2, 24 teeth were prepared with a 1/4-round bur in a low-speed
      handpiece and then acid etched. In group 3, 24 teeth were prepared by high-speed
      (160 PSI) microabrasion using 50 mu alpha alumina particles in a KCP 2000
      machine. In each group, 12 teeth were sealed with a filled sealant and 12 teeth
      with an unfilled sealant. All the teeth were stored in artificial saliva for 7
      days and thermocycled for 2000 cycles. Teeth were then sealed apically and coated
      with nail varnish 1 mm from the margins and stained in 1% methylene blue for 24
      h. Each tooth was sectioned in three locations and ranked (0-3) for microleakage.
      RESULTS: There were 216 sections and 66% showed no leakage. CONCLUSIONS: Chi
      square statistical analysis of the data led to the following conclusions: 1)
      superior results were obtained when the tooth surfaces were prepared by a bur, 2)
      conventionally and KCP 2000-prepared tooth surfaces yielded similar results, and
      3) the unfilled sealant was superior to the filled sealant.

PMID- 9635313
TI  - Effects of formocresol alone vs. formocresol with eugenol on macrophage adhesion
      to plastic surfaces.
AB  - PURPOSE: The purpose of this study was to compare the in-vitro effects of a
      European-based formocresol formulation that incorporates eugenol with formocresol
      alone on the adhesion of macrophages to plastic surfaces. METHODS: Macrophages
      were obtained from Wistar rats. The adherence capacity of macrophages to a
      plastic surface was determined. Assays were carried out in Eppendorf tubes
      incubated for 15 min at 37 degrees C in a humidified atmosphere of 5% CO2. The
      adherence index was calculated. RESULTS: Results showed that both
      formocresol/eugenol and formocresol alone significantly decreased the adherence
      index of macrophages. The formocresol formulation that incorporated eugenol was
      more potent in inhibiting macrophage adhesion than formocresol alone.
      CONCLUSIONS: Taking into account that adherence to a substrate is the first step
      in the phagocytic process of macrophages and in antigen presentation, both
      formocresol formulations could inhibit macrophage function and modulate immune
      and inflammatory responses in dental pulp and periapical tissues.

PMID- 9635314
TI  - The impact of WIC dental screenings and referrals on utilization of dental
      services among low-income children.
AB  - PURPOSE: This cross-sectional study examined whether referrals from nondental
      health professionals impacted utilization of dental services by low-income
      populations. METHODS: A sample of 309 mothers enrolled in the Women, Infant, and
      Children (WIC) clinic in Jackson County, Missouri, completed a self-administered,
      32-item questionnaire to assess the mother and child's oral health behavior and
      past use of dental services. Dental utilization, the primary dependent variable,
      was defined as whether or not the child had ever been to a dentist. RESULTS:
      Findings showed 27% of the children in the sample had been referred for dental
      care. Bivariate analysis indicated that a dental referral, age of the child, age
      of the mother, mother's perceived dental need for the child, household size,
      number of children in the household, and dental insurance for the child were
      associated with a child having a dental visit. Logistic regression, however,
      indicated that only age was significantly related to utilization. CONCLUSION: The
      results showed a strong effect of increasing age being related to dental
      utilization, while additional research is needed to clarify the importance of WIC
      referrals.

PMID- 9635315
TI  - A study of small superficial capillary hemangiomas on the lips in children.
AB  - PURPOSE: This study describes 77 small vascular lesions on the lips of 74
      children and adolescents. RESULTS: Of the 77 lesions, 70% were on the lower lip
      and 30% on the upper. The diameter range was 0.5-5.0 mm (mean 1.4 mm). On both
      lips the lesions were in the vermilion zone, close to the border with the skin.
      The surface of the lesions was smooth and slightly raised, and varied in color
      from red (49%) through bluish red (45%) to purple (6%). The borders were well
      defined in most cases. The histology of the lesions was consistent with capillary
      hemangioma. Small superficial capillary hemangiomas (SSCH) in this study behaved
      differently from most hemangiomas and vascular malformations in that they did not
      increase in size, and were persistent in the age group in which most hemangiomas
      are reported to involute or disappear. The gender distribution of SSCH also
      differed from the female predominance in hemangioma. SSCH is a solitary benign
      lesion on the lips of children and adolescents, which has not been separately
      classified before. CONCLUSIONS: Based on the differences from hemangioma in
      gender distribution, size, border definition, and growth characteristics, it is
      suggested that SSCH be classified as a variant or a subgroup of hemangioma.

PMID- 9635316
TI  - Delayed tooth eruption in congenital hypertrichosis lanuginosa.

PMID- 9635317
TI  - Multiple pre-eruptive intracoronal radiolucent lesions in the permanent
      dentition: case report.

PMID- 9635318
TI  - Odontodysplasia: report of two cases.

PMID- 9635319
TI  - Pycnodysostosis: orofacial manifestations in two pediatric patients.

PMID- 9635320
TI  - Otodental syndrome: three familial case reports.

PMID- 9635321
TI  - How outcomes and evidence can strengthen the role of the pediatric dentist.

PMID- 9635322
TI  - Oral health outcomes and evidence-based care.

PMID- 9635323
TI  - Outcomes and the scientific basis of clinical care.

PMID- 9635324
TI  - Pediatric dental treatment outcomes: the importance of multiple perspectives.

PMID- 9635325
TI  - 1997 C. H. McCloy Research Lecture: Knowledge is more than we can talk about:
      implicit learning in motor skill acquisition.
AB  - This article discusses the acquisition of knowledge about environmental
      regulatory features that guide the selection and execution of movements involved
      in performing open motor skills. First, empirical evidence related to the visual
      search characteristics of skilled and novice performers is considered to
      demonstrate that learning environmental regulatory features is an important part
      of performing an open motor skill. Then, the hypothesis is proposed and discussed
      that environmental regulatory features can, and probably should, be learned
      implicitly, which means the features can be learned and used, even though the
      learner is not consciously aware of the specific characteristics of those
      features. This article also discusses laboratory-based experiments that provide
      evidence supporting this hypothesis and presents implications for developing
      instructional strategies and practice conditions.

PMID- 9635326
TI  - Visual search strategy, selective attention, and expertise in soccer.
AB  - This research examined the relationship between visual search strategy, selective
      attention, and expertise in soccer. Experienced (n = 12) and less experienced (n
      = 12) soccer players moved in response to filmed offensive sequences. Experiment
      1 examined differences in search strategy between the two groups, using an eye
      movement registration system. Experienced players demonstrated superior
      anticipation in 3-on-3 and 1-on-1 soccer simulations. There were no differences
      in search strategy in 3-on-3 situations. In 1-on-1 simulations, the experienced
      players had a higher search rate, involving more fixations of shorter duration,
      and fixated for longer on the hip region, indicating that this area was important
      in anticipating an opponent's movements. Experiment 2 examined the relationship
      between visual fixation and selective attention, using a spatial occlusion
      approach. In 3-on-3 situations, masking information "pick up" from areas other
      than the ball or ball passer had a more detrimental effect on the experienced
      players' performances, suggesting differences in selective attention. In 1-on-1
      situations, occluding an oncoming dribbler's head and shoulders, hips, or lower
      leg and ball region did not affect the experienced players' performances more
      than the less experienced group. The disparities in search strategy observed in
      Experiment 1 did not directly relate to differences in information extraction.
      Experiment 3 used concurrent verbal reports to indicate where participants
      extracted information from while viewing 3-on-3 sequences. Experienced players
      spent less time attending to the ball or ball passer and more time on other areas
      of the display. Findings highlight the advantages of integrating eye movements
      with more direct measures of selective attention.

PMID- 9635327
TI  - The effect of nonregulatory stimuli on the triple jump approach run.
AB  - The purpose of this experiment was to examine the approach run of the triple
      jump. Specifically, we examined the effect of nonregulatory stimuli (Gentile,
      1972) on two different ability levels in performing the triple jump approach run.
      These nonregulatory constraints (situational factors such as those seen in actual
      competition) were employed in three jumping conditions: Control (to obtain
      baseline performance measures), Distance (where participants attempted to obtain
      as great a jump as possible), and Accuracy (participants attempted to be as
      accurate as possible on takeoff without sacrificing distance). The results showed
      that the footfall position variability for all conditions was similar to those
      previously reported for the long jump approach run. However, in compliance with
      the nonregulatory constraints, participants altered other performance parameters
      in executing the approach run. The situational factors created changes that
      revealed themselves in foot placement on the takeoff board at the end of the
      approach run (foot position constant error and number of fouls increased for the
      Distance condition) and decreased horizontal velocity at takeoff in the Accuracy
      condition. Changes in performance parameters were related to the context in which
      the skill was performed and may further reflect changes made by jumpers in the
      course, such as a visual-motor task in competition. We suggest that the
      characteristics of the approach run may not be fully revealed by the pattern of
      footfall variability only, as has been suggested in previous work (e.g., Lee,
      Lishman, & Thomson, 1982), but that the situation under which the jump is
      performed may have a significant effect on the performance parameters that emerge
      in executing this type of motor skill.

PMID- 9635328
TI  - Motor performance and motor learning as a function of age and fitness.
AB  - Past studies have shown that electroencephalographic alpha activity increases as
      people learn to perform a novel motor task. Additionally, it has been suggested
      that motor performance and learning decline as people age beyond 60 years, and it
      has been hypothesized that physical fitness may attenuate this decline through
      its impact on the cerebral environment. This study was designed to replicate past
      research by assessing changes in alpha activity as a function of learning and to
      extend past research by examining differences in motor performance, motor
      learning, and alpha activity as a function of age and fitness. VO2max was
      assessed in 41 older (ages 60-80 years) and 42 younger (ages 20-30 years)
      participants. Participants were randomly assigned to experimental or control
      conditions, which differed in the amount of practice received. Participants
      performed trials on the mirror star trace on both an acquisition and a retention
      day. Results indicated that younger participants performed better and had greater
      learning than older participants. Fitness was not found to impact either
      performance or learning. Participants in the experimental group improved more
      than those in the control group and maintained this difference at retention,
      which suggests that learning occurred. Associated with these improvements in
      performance capabilities was an increase in alpha power.

PMID- 9635329
TI  - The development of in-service teachers' knowledge of a constructivist approach to
      physical education: teaching beyond activities.
AB  - The purpose of this paper is to describe three aspects of learning a movement
      approach that were salient and initially problematic for 1 experienced teacher, 2
      early career teachers, and 1 student teacher. A constructivist perspective was
      the theoretical base. Across 3 years, the researcher conducted 11 weeks of
      observations, 15 formal interviews, 3 group interviews, and daily informal
      interviews. Three problematic aspects were: (1) knowing to what extent they
      should give information and tell children what to do when teaching less
      structured content, (2) knowing the whole of the approach and how components
      connected, and (3) knowing content (i.e., pedagogical content knowledge) in
      enough depth and detail. Knowledge development was facilitated by more
      experienced teachers, experience, and a set of key ideas.

PMID- 9635330
TI  - Parental beliefs and children's moderate-to-vigorous physical activity.
AB  - The present study was guided by the Family Influence Model to examine the role of
      parental beliefs in their children's moderate-to-vigorous physical activity
      (MVPA). The specific purposes were to (1) examine the nature of a parental belief
      system that may be relevant to children's MVPA participation, (2) determine if
      parental beliefs regarding their children's MVPA are gender related, (3) examine
      the relationship between parents' exercise behavior and children's MVPA
      participation, and (4) investigate the strength of the relationship between
      parental beliefs and children's self-reported MVPA. The participants for this
      study included 81 children (26 girls and 55 boys) between the ages of 11 and 15
      years and their parents (n = 142). Significant findings were: (1) descriptive
      evidence of a parental belief system for children's MVPA existed, (2) mothers and
      fathers differed in their MVPA-related beliefs for their child, (3) no
      relationship was found between parents' exercise behavior and children's MVPA
      participation, and (4) parental beliefs relating to their children, especially
      perceptions of competence and a task orientation, were significantly related to
      the amount of children's MVPA participation. These findings support the basic
      tenets of the Family Influence Model and suggest that parental beliefs should be
      taken into consideration to better understand the psychosocial process underlying
      children's participation in fitness-oriented physical activity.

PMID- 9635331
TI  - The relationship between competitive anxiety, achievement goals, and motivational
      climates.
AB  - The purpose of this study was to examine the relationships of achievement goal
      orientations and perceived motivational climate to perceptions of the intensity
      and direction of competitive state anxiety in a sample of university athletes
      representing various team sports. Although some studies have demonstrated that
      task orientation and mastery climate are associated with adaptive emotional
      patterns and ego orientation and performance climate are linked to less adaptive
      emotions, others have not verified these findings. In the present study,
      structural equation modeling was used to test these links. The results showed
      that perceptions of a performance climate were associated with ego orientation,
      whereas perceptions of a mastery climate were linked to task orientation.
      Furthermore, no significant links were found between task orientation and
      direction of competitive anxiety, while it was shown that the impact of ego
      orientation on the intensity and direction of cognitive and somatic anxiety was
      exerted through self-confidence. No significant direct links were found between
      motivational climates and competitive anxiety, thus implying that motivational
      climates may have an indirect impact on affective responses through the different
      goal orientations. The findings of the present study are discussed along with
      suggestions for examining situational and individual difference variables that
      may explain the relationships between intensity and direction of competitive
      anxiety and achievement goals and motivational climates.

PMID- 9635332
TI  - Gender differences in preferences for coaching as an occupation: the role of self
      efficacy, valence, and perceived barriers.
AB  - This study investigated gender differences in the role of self-efficacy,
      occupational valence, valence of coaching, and perceived barriers in preference
      to coach at the high school, 2-year college, Division III, Division II, and
      Division I levels. The participants, 191 Big Ten university basketball players
      (94 men, 97 women), responded to a specially constructed instrument. The genders
      did not differ in their coaching self-efficacy, preferred occupational valence,
      and perceived barriers. Relative to men, women perceived greater valence in
      coaching (p < .001). Women with a female coach perceived greater valence in
      coaching (p < .05) and expressed less concern with perceived discrimination (p <
      .05) than those with a male coach. Perceived self-efficacy and preferred
      occupational valence were differentially related to the desire to coach at
      various levels. Working Hours most negatively affected the desire to coach at
      every level (R > .20).

PMID- 9635333
TI  - Nasal strips and mouthpieces do not affect power output during anaerobic
      exercise.

PMID- 9635334
TI  - A modified version of the Rockport Fitness Walking Test for college men and
      women.

PMID- 9635335
TI  - Children's age moderates the effect of practice variability: a quantitative
      review.

PMID- 9635336
TI  - Acute effects of ambient ozone on asthmatic, wheezy, and healthy children.
AB  - Southern California children (10 to 12 years old) participated in a two-season
      study to assess the potential acute respiratory effects of ambient ozone (O3).
      Asthmatic (n = 49), wheezy (n = 53), and healthy (n = 93) children completed a
      four-day (Friday through Monday) study protocol, once in spring and again in
      summer, that included the use of daily activity and symptom diaries, heart rate
      recording devices, personal O3 samplers, and maximal effort spirometry several
      times per day. Data from regional monitoring stations were used to establish
      ambient hourly O3 concentrations. Analyses revealed that the children spent more
      time outdoors and were more physically active in the spring. Girls spent less
      time outdoors and were less physically active than boys. Personal O3 samplers
      correlated poorly with, and generally gave lower readings than, outdoor ambient
      monitors. Higher personal O3 exposures were associated generally with increased
      inhaler use, more outdoor time, and more physical activity. Children with asthma
      spent more time outdoors and were more active in the spring on high-O3 days
      (measured by personal sampler), and had the most trouble breathing, the most
      wheezing, and the most inhaler use on these days. Activity pattern data suggested
      that children with asthma protected themselves by being less physically active
      outdoors during the summer on high-O3 days. Wheezy children had the most trouble
      breathing during the summer on low-O3 days (measured by personal sampler).
      Observed relationships between O3 and pulmonary function were erratic and
      difficult to reconcile with existing knowledge about the acute respiratory
      effects of air pollution. We conclude that although asthmatic and wheezy children
      behave differently from their healthy peers with regard to symptoms and patterns
      of activity when challenged by ambient ozone, the nature of these changes remains
      inconsistent and ill-defined.

PMID- 9635337
TI  - New report and pilot studies on Chlamydia.

PMID- 9635338
TI  - Escherichia coli O157 in Somerset.

PMID- 9635339
TI  - Rise in falciparum malaria imported from east Africa.

PMID- 9635340
TI  - Hepatitis C virus infection in children.

PMID- 9635341
TI  - Protecting health care workers against bloodborne viruses.

PMID- 9635342
TI  - Enhanced surveillance of meningococcal disease in five English regions: first
      quarter 1998.

PMID- 9635343
TI  - Outbreak of Vero cytotoxin producing Escherichia coli O157 infection in Dorset.

PMID- 9635344
TI  - AIDS and HIV infection in the United Kingdom: monthly report.

PMID- 9635345
TI  - The future belongs to those who plan for it.

PMID- 9635346
TI  - The use of pure follicle stimulating hormone during the luteal phase to increase
      success of ovulation induction in poor responders: a pilot study.

PMID- 9635347
TI  - Medical practice evaluation: adding a physician assistant.

PMID- 9635348
TI  - Yet another suggestion to improve quality of care.

PMID- 9635349
TI  - [The tendency of antibiotic therapy in dental and oral surgical practice].
AB  - The large number of dental inflammations can be explained by the bad general
      dental condition in Hungary. Antibiotics have been used more extensively here
      then in several other countries. The recently introduced antibiotics are
      preserving the beneficial effects of the older ones with less side effects. The
      oral flora and their resistance to antibiotics are very different in certain
      countries. Therefore the professional protocols of the stomatological
      inflammations followed by certain countries cannot be applied directly in other
      countries. The changing resistance and the appearance of the new antibiotics make
      necessary the general evaluation of different antibiotics from time to time. The
      patients, the doctors and the society has the same interest: to get or provide
      more and more fast, safe and effective treatment. But to achieve this objective
      the dentists have to reevaluate their treatment habits accordingly.

PMID- 9635350
TI  - [Sealing effectiveness of root canal fillings pretreated with Gluma Dentin Bond].
AB  - The root canals of 41 extracted human teeth with single canal were shaped using
      hand instruments. The canal walls of test roots [22] were pretreated with Gluma
      resin. All of the canals were filled using the same method. The sealing ability
      of root canal fillings was evaluated by dye penetration test and the morphology
      of canal walls was observed by SEM. In the experimental group the dentin bond
      covered the canal walls completely and the entrances of dentin tubules were
      obturated. The dentin bond can be observed in the dentinal tubules as well. The
      mean value of dye penetration was 0.53 mm for the control group and 0.37 mm for
      the test group. The Gluma pretreatment of root canals increased the sealing
      ability of AH 26, however, the difference was statistically not significant.

PMID- 9635351
TI  - [Extensive intraoral cicatrization treated by microsurgery].
AB  - Extensive intra-oral burns are very rare injuries. The microstomia resulting from
      the advanced cicatrization of the mucosa makes it difficult for the patient to
      eat and impossible to take care of his teeth. The traditional operation for
      widening the oral orifice was not sufficient because of the extensive scarring of
      the bucca. In the first operation the authors substituted the mucosa of the lip
      and the bucca of one side with splitted jejunum. Because of the advancing
      scarring another operation was performed and the mucosa of the other side of the
      bucca and the angle of mouth was substituted with a forearm graft.

PMID- 9635352
TI  - The types of neurons of the somatic oculomotor nucleus in the European bison.
      Nissl and Golgi studies.
AB  - The neuronal structure of the somatic oculomotor nucleus (SON) was studied on the
      basis of Nissl and Golgi preparations, obtained from mesencephalons of 4 European
      bisons. We distinguished four types of neurons in the investigated nucleus: 1.
      The large multipolar nerve cells with 5-8 thick dendritic trunks and a thin axon
      which emerges directly from the soma. These are the most numerous neurons in the
      SON. 2. The small multipolar neurons. These cells have 4-6 thick dendritic
      trunks. An axon arises mostly from initial segment of one of the dendrites. This
      type represents about 8% neurons of SON. 3. The triangular neurons. From
      perikaryon 3 thick dendritic trunks emerge. A thin axon arises directly from the
      cell body. These cells make about 10% neurons of SON. 4. The pear-shaped cells
      which have 1 or 2 dendritic trunks concentrate at one pole of the neurons. In the
      SON there are about 2% pear-shaped cells. Their features correspond to the
      features attributed by many authors to the interneurons.

PMID- 9635353
TI  - Morphology of brain stem lesion and bera findings after 60Co irradiation.
AB  - Ionizing rays, utilized in radiological diagnostics and oncological therapy
      affect the central nervous system and may injure auditory pathways and cause
      hearing disturbances which vary in intensity. On the basis of a stereotactic
      atlas of the brain of a guinea pig, the trapezoid and geniculate bodies were
      identified in the skull X-ray pictures. The irradiated region was found to have
      10 x 6 x 5 mm in dimensions and to be situated at the depth of 11 mm away from
      the animals occiput. After introductory recording of the potentials obtained from
      the brain stems (BERA), the stems of 60 guinea pigs were irradiated in the groups
      with the doses of 5, 10, 20 Gy. The hearing potentials from the brain stems were
      recorded on the 1st, 4th, 10th, 21st and 84th day after irradiation. The findings
      of measurements of hearing potentials were compared with the morphologic picture
      of the brain stems in the examined animals.

PMID- 9635354
TI  - Mandible measurements in aspect of some muscles attachment.
AB  - The paper deals with a part of anatomical research in aspect of clinical
      evaluation of lowering mandible muscles attachments (mylohyoid m, digastric m,
      geniohyoid m.) and genioglossus muscle. The research was conducted on 183 adult
      males and 117 females crania. The variance analysis of Tukey's revealed, that
      crania traits established on the basis of statistical parameters of breadth
      length index, and visceral cranium height-breadth index, are significant. In
      order to establish statistical characteristics of examined traits, including into
      research sexual dimorphism and bilateral differences is also very important.

PMID- 9635355
TI  - Microvasculature of the human fetal laryngeal anterior commissure.
AB  - The vascular pattern of the injected with Mercox human fetal larynges, especially
      of the anterior commissure and surrounding it area, was analysed within the
      horizontal and frontal sections under a light microscope. The main result of our
      study was confirmation of existence of the avascular "plane zero" situated above
      the anterior commissure, which separates that structure from the supraglottic
      tier. That finding i.e. avascular separation between teh middle and upper
      laryngeal compartments, already present in the fetal period, has clinical
      implications as far as the spread of neoplastic process within the larynx is
      cancerued.

PMID- 9635356
TI  - Selected cases of atypical course of renal and gonadal arteries and veins.
AB  - In studies conducted on material comprising 209 individuals of both sexes at the
      age of 20 weeks to 90 years, five cases were found with atypical course of renal
      and gonadal vessels along with developmental anomalies of the kidneys and
      ureters. In three individuals with these anomalies of vessels and ureters some
      accompanying complicated organic heart diseases were also detected.

PMID- 9635357
TI  - Morphology of the abdominal hemolymph nodes in the Wistar rats.
AB  - In 26 Wistar rats the morphology of 30 renal and 20 splenic lymph nodes were
      investigated. The left renal nodes are usually singular as compared to multiple
      right renal nodes. Microscopically they present segmental structure with
      erythroidal elements located mainly in the medullary cords. The splenic nodes, 1
      to 5 in number do not show segmental structure but have uniformly dispersed
      erythroidal elements.

PMID- 9635358
TI  - Variation of the structure and course of the interlobular arteries in human
      kidney.
AB  - In microangiograms and clearing preparations obtained from 25 adult human
      kidneys, the variations of number, origin, length and ramification pattern of the
      interlobular arteries were investigated. In the examined material, the
      interlobular arteries arose from the arcuate arteries at various angles, most
      frequently as a common trunk dividing in its course into 2 to 5 proper
      interlobular arteries. Their length was varied in the particular portions of the
      renal cortex and correlated with its thickness.

PMID- 9635359
TI  - Development of ascending colon in human fetal period.
AB  - On the material of 178 fetuses of both sexes, ascending colon development in
      fetal period was studied. Variability of its measurements, shapes as well as of
      peritoneal and topographic proportions were traced.

PMID- 9635360
TI  - Changeability of internal sexual organs of human fetuses basing on their image
      computer analysis.
AB  - The aim of the paper is computer transformation of the transversal research
      results of male (214) and female (178) genital internal organs (examined in 4
      months's intervals) in a way enabling longitudinal evaluation.

PMID- 9635361
TI  - Morphometric study of the lens in staged human embryos.
AB  - In 32 embryos of developmental stages 13 to 23 the measurements of the eye and
      lens were made. It was shown that the speed of growth of the eye and lens is at a
      maximum between 19 and 23 stages. Beginning from stage 19 the lens acquires
      ellipsoidal shape.

PMID- 9635362
TI  - The caroticobasilar artery in species of order Perissodactyla.
AB  - The caroticobasilar artery was investigated in animals of order Perissodactyla,
      in species of Equidae family, and in lowland tapir of Tapridae family. It was
      found that the caroticobasilar artery forms homolateral or bilateral anastomosis
      between the basilar and internal carotid arteries or in horse and other species
      of Equidae family between basilar and caudal intercarotid arteries. The
      caroticobasilar artery was found in all species of Equidae family, in all zebras
      and in one tapir.

PMID- 9635363
TI  - Variations in testicular arteries in fetuses and adults.
AB  - An investigation was carried out of 100 human male individuals at the age of 20
      hbd to 28 hbd and of 18 to 90 years. Attention was paid to the fact whether these
      blood vessels commenced in the aorta or renal artery, to the relation of
      testicular arteries to the trunk of vena cava inverior, and to their course vis a
      vis that of the renal veins. Four most common variations in the course of these
      vessels were identified, and variations in their basic types seen in our material
      were described.

PMID- 9635364
TI  - Anomaly of the human left renal vein.
AB  - A case of the anomalous course of the renal vein is described. The vein trunk is
      divided into two crura: a thinner, anterior which passes in front of the
      abdominal aorta, and a thicker, posterior which lies behind the aorta. Both crura
      terminate in the inferior vena cava.

PMID- 9635365
TI  - Metric features of the iliopsoas muscle in late fetuses and adults.
AB  - Differences in structure of iliopsoas muscle were documented in studies performed
      on 12 human fetuses, aging 37 to 40 weeks of gestational life and on 20 adult
      individuals. Results of measurements performed on the muscle were compared
      between fetuses of the perinatal age and adult individuals. Indirectly, the
      comparison allowed to draw conclusions as to changes in the muscle structure
      which take place in between the two developmental stages. The process was
      monitoring applying the metric techniques of studies and statistical
      interpretation of the results.

PMID- 9635366
TI  - Minors: a medical care dilemma.

PMID- 9635367
TI  - Medical musical chairs.

PMID- 9635368
TI  - The JIM interview John G. Clarkson, MD.
AB  - Located in one of the fastest growing areas in the United States, the University
      of Miami School of Medicine sits poised to capitalize on an expanding hemispheric
      economy. At the same time, the school must also accommodate a burgeoning
      competition for Medicare patients with for-profit hospitals. At the helm of the
      University of Miami School of Medicine is John G. Clarkson. Clarkson had served
      as chairman of the Department of Ophthalmology, Bascom Palmer Eye Institute and
      medical director of the Anne Bates Leach Eye Hospital from 1991 to 1995, when he
      became dean. He replaced Dean Bernard Fogel who held the position for 14 years.
      Interviewed in his office in sunny Miami, Clarkson discussed Miami's approach to
      expanding the school's foreign and domestic patient base, developing alliances,
      and trying to increase the medical center's profile amongst an increasingly
      diverse population.

PMID- 9635369
TI  - CXC chemokine modulation of angiogenesis: the importance of balance between
      angiogenic and angiostatic members of the family.

PMID- 9635370
TI  - The effects of stem cell factor and granulocyte colony stimulating factor therapy
      on the activity of the neutrophil NADPH oxidase enzyme system.
AB  - BACKGROUND: To explore the effect of cytokine therapy on the NADPH oxidase in
      mature myeloid cells, we isolated neutrophils from patients receiving recombinant
      human granulocyte colony stimulating factor (G-CSF) and recombinant human stem
      cell factor (SCF) and evaluated oxidase activity. All patients had relapsed
      neoplastic disease and were at least 3 three weeks since the last course of
      chemotherapy or cytokine therapy. METHODS: Stimulus induced superoxide anion (O2
      ) production in response to PMA (200 ng/mL), fMLP (1 mumol/L), platelet
      activating factor (PAF, 2 mumol/L) priming of the fMLP induced response, and
      opsonized zymosan OZ (1 mg/mL) was measured. Polymorphonuclear leukocyte (PMN)
      subcellular components were prepared, after nitrogen cavitation, by separation on
      discontinuous sucrose gradients and NADPH oxidase activity was assessed in a SDS
      cell-free system. RESULTS: SCF had no effect on the activity of the neutrophil
      oxidase. Neutrophils isolated from patients treated with G-CSF and stimulated
      with PMA produced less (superoxide anion) O2- after therapy. PAF priming of the
      fMLP induced respiratory burst was also reduced after therapy with G-CSF.
      Subcellular NADPH oxidase activity was reduced before cytokine therapy commenced.
      This activity did not improve with cytokine treatment. CONCLUSIONS: It appears
      likely from this study that G-CSF therapy, with or without SCF, does not cause
      significant enhancement of neutrophil NADPH oxidase activity.

PMID- 9635371
TI  - Keratinocyte-specific expression of human thrombomodulin in transgenic mice:
      effects on epidermal differentiation and cutaneous wound healing.
AB  - BACKGROUND: Thrombomodulin is a cell-surface glycoprotein that regulates
      coagulation and fibrinolysis. Expression of thrombomodulin by epidermal
      keratinocytes is tightly regulated during squamous differentiation and cutaneous
      wound healing. METHODS: To determine the consequences of overexpression of
      thrombomodulin on squamous differentiation and wound healing in vivo, we
      expressed full-length human thrombomodulin in transgenic mice using the human
      keratin 14 promoter. Human thrombomodulin was detected in keratinocytes of
      transgenic mice by immunohistochemistry and protein C activation assays. Full
      thickness cutaneous wounds were created on the dorsum of transgenic mice and
      nontransgenic littermates, and allowed to heal for up to 35 days. RESULTS:
      Transgenic mice had normal viability and appeared healthy up to one year of age.
      In the skin, human thrombomodulin was expressed in basal and suprabasal
      keratinocytes, with variable expression in the outer root sheath of hair
      follicles. Thrombomodulin activity in neonatal epidermis was 2.5- to 3-fold
      higher in transgenic mice than in nontransgenic littermates (p < 0.01). In
      cutaneous wounds, human thrombomodulin was expressed in migrating neoepidermal
      keratinocytes. No differences in keratinocyte migration or re-epithelialization
      were observed between transgenic and nontransgenic mice, but transgenic mice
      exhibited delayed collagen bundle deposition within the wound matrix.
      CONCLUSIONS: These findings demonstrate that keratinocyte thrombomodulin supports
      activation of protein C, and that thrombomodulin activity in epidermis can be
      increased by keratinocyte-specific expression of human thrombomodulin in
      transgenic mice. Expression of human thrombomodulin in keratinocytes does not
      impair normal squamous differentiation or re-epithelialization of cutaneous
      wounds, but may modulate collagen reconstitution of the wound matrix.

PMID- 9635372
TI  - Fibroblasts from mice with progessive ankylosis proliferate excessively in
      response to transforming growth factor-beta 1.
AB  - BACKGROUND: Murine progressive ankylosis (MPA) is a spontaneous arthropathy that
      produces ankylosis of peripheral and spinal joints in mice homozygous for the
      gene ank. This animal model bears a striking resemblance clinically,
      radiographically, and histologically to ankylosing spondylitis. Phosphocitrate
      (PC) is the only treatment known to significantly delay disease progression in
      MPA. Transforming growth factor-beta (TGF-beta) is important for both
      developmental bone formation and fracture healing, and has been detected in
      biopsy specimens from sacroiliac joints of patient with ankylosing spondylitis.
      We hypothesized that TGF-beta might be involved in the pathogenesis of MPA.
      METHODS: We compared the proliferative response of resting fibroblasts from
      normal and MPA mice to TGF-beta 1 as measured by 3H-thymidine incorporation and
      the effect of PC on that response. Cells were cultured with 10% serum as a
      positive control. The mouse fibroblast cell line, BALB/3T3, controlled for
      culture conditions. RESULTS: MPA and normal fibroblasts responded similarly to
      serum. MPA fibroblasts proliferated significantly better in TGF-beta 1 than the
      poorly responsive normal mouse fibroblasts. PC, at 10(-3) mol/L, inhibited the
      TGF-beta 1-induced proliferation of MPA and 3T3 cells, but had no effect on
      normal fibroblasts. CONCLUSIONS: MPA fibroblasts proliferate excessively to TGF
      beta 1 in vitro. This effect could be caused by altered TGF receptors, changes in
      signal transduction, or impaired inhibition of the TGF-beta signal. This
      excessive response is blocked by PC. These results give further clues as to how
      PC inhibits the progression of ankylosis in MPA.

PMID- 9635373
TI  - Serum levels of a prostaglandin and a leukotriene after thermal mud pack therapy.
AB  - BACKGROUND: Mud pack therapy (MPT) influences the serum levels of several
      cytokines involved in chondrocyte metabolism and in the pathogenesis of
      osteoarthrosis. In fact, we have observed decreases of IL-1 and TNF-alpha,
      involved in cartilage inflammation and destruction, and increases of IGF-1 that
      have a protective influence on the cartilage. It is known that in osteoarthrosis
      MPT is also able to decrease pain, largely attributable to the inflammatory
      response. METHODS: We enrolled 31 subjects undergoing MPT and collected blood
      samples before and after the therapy to assay serum levels of prostaglandin
      (PGE2) and leukotriene (LTB4) compounds with potent inflammatory and algesic
      properties. RESULTS: The study shows a decrease in PGE2 and LTB4 serum levels in
      all the samples after MPT with no correlation between the PGE2 and LTB4
      decreases. CONCLUSIONS: Mud pack therapy exerts a protective effect on the
      cartilage and is able to induce pain relief by reducing the inflammatory
      reaction.

PMID- 9635374
TI  - Acetaldehyde inhibits chymotrypsin and serum anti-chymotrypsin activity.
AB  - BACKGROUND: Chymotrypsin (CT) and CT-like enzymes contribute to the dynamics of
      metabolism by their participation in digestion, peptide hormone generation and
      catabolism, fertilization of ova and inhibition of thrombin-induced platelet
      aggregation, among other processes. The frequency of pancreatitis is observably
      higher in alcoholics, and pancreatic enzymes have been associated with localized
      vascular damage, thrombosis and pancreatic necrosis. METHODS: Since CT is a major
      pancreatic enzyme and may serve as a link between pancreatitis, coagulopathy, and
      alcoholism, the affect of acetaldehyde (AcH) the primary metabolite of ethanol,
      upon the enzyme and upon the influence of human serum thereon was studied.
      RESULTS: It was observed that CT activity upon glutaryl-L-phenylalanine-b
      naphthylamide was inhibited to the extent of 23.7%, 52.5%, and 96.7% by 44.7,
      89.4, and 447 mmol/L AcH in a fluorometric assay whereby the enzyme was dialyzed
      to remove excess AcH prior to assay. The p values were < 0.04. Aliquots of human
      serum (10 microL, 20 microL, 30 microL, 40 microL, 50 microL, and 100 microL)
      inhibited 40 micrograms of CT by 13%, 37.7%, 65.3%, 89.8%, and 92.8%,
      respectively (n = 6; p = < 0.05). The serum did not hydrolyze the fluorogenic
      substrate. On the other hand, AcH added to serum at 447, 224, 112, or 56 mmol/L
      resulted in 42.6%, 42.6%, 52.9%, and 60.3% inhibition of CT relative to a 69.1%
      inhibition of the enzyme by serum alone (n = 6; = p < 0.01). CONCLUSIONS: These
      data show that AcH clearly decreases the antichymotryptic activity of serum
      (consisting of alpha 1-proteinase inhibitor, alpha 1-antichymotrypsin, and alpha
      2-macroglobulin). The incomplete inactivation of chymotrypsin by serum and
      partial inactivation of CT inhibitor(s) by AcH suggest the possibility that CT
      leaked into the circulation, (in alcoholic pancreatitis) may be available in
      blood to lower the clotting potential induced by thrombin-activated platelets,
      and that a greater amount of CT might be available in the blood of alcoholics,
      thereby contributing, in part, to the prolongation of clotting times.

PMID- 9635375
TI  - Diagnostic characteristics of cerebrospinal fluid analysis for secondary
      menigitis in HIV-infected adults.
AB  - BACKGROUND: When human immunodeficiency virus (HIV)-infected patients present
      with neurologic problems, lumbar puncture and cerebrospinal fluid (CSF) analysis
      are often performed, usually to rule-out the presence of meningitis. However, the
      test characteristics of CSF analyses in this population are unknown. METHODS: To
      examine the diagnostic characteristics of CSF analyses for secondary causes of
      meningitis in HIV-infected adults, we performed a case-control study of 322 HIV
      infected adults who received diagnostic lumbar puncture in an urban academic
      hospital from 1989 to 1992. Using multivariable logistic regression analyses, we
      determined the independent CSF correlates of cryptococcal and other types of
      secondary meningitis. RESULTS: Eighty percent were men who had sex with men, 89%
      were white, and 85% had AIDS. Thirty-seven case-subjects had a secondary cause of
      meningitis though none had bacterial or tuberculous meningitis. Excluding the
      india ink as a candidate variable, logistic regression analysis identified 2
      independent CSF correlates of secondary meningitis: the leukocyte count (odds
      ratio [OR] per 10 cells, 1.2; 95% confidence interval [CI], 1.1 to 1.3), and the
      CSF-to-serum glucose ratio (OR per 0.10 units, 0.61; CI, 0.43 to 0.88). The areas
      (+/- SD) under the receiver operating characteristic curves were 0.76 +/- 0.05
      and 0.72 +/- 0.05, respectively. CONCLUSIONS: In similar clinical settings, these
      findings may help clinicians assess the probability of secondary meningitis in
      HIV-infected patients when initial CSF results first become available.

PMID- 9635377
TI  - Disputed claims for pertussis vaccine injuries under the National Vaccine Injury
      Compensation Program.
AB  - BACKGROUND: The National Vaccine Injury Compensation Program (NVICP) provides no
      fault compensation to victims of serious untoward vaccine reactions under the
      supervision of the Department of Health and Human Services (HHS). Special Masters
      of the Court of Federal Claims settle compensation disputes that arise between
      applicants and program administrators. The majority of published NVICP claim
      decisions concern disputes over the cause of neurologic illness or unexpected
      infant death following pertussis vaccination. METHODS: Information was collected
      from the published decisions to determine the medical characteristics of cases in
      which injuries were legally attributed to pertussis vaccination. Because of
      practical and statutory restrictions on the application process and the evolving
      nature of HHS claim denials, vaccinees in the disputed cases are not
      representative of all vaccine casualties, or of all NVICP applicants. RESULTS:
      Injuries were blamed on pertussis vaccine in 542 claims disputed by HHS. Claims
      asserted that pertussis vaccine caused seizure disorders (333 claims, 189 were
      awarded compensation), anaphylaxis (7 claims, 6 awards), hypotonic/hyporesponsive
      episodes or other injuries leading to early death (107 claims, 73 awards), and
      long-term neurologic disease (51 claims, 18 awards). CONCLUSIONS: Assertions that
      pertussis vaccine caused unexpected infant death (other than anaphylaxis),
      seizure disorders, and long-term neurologic damage are inconsistent with
      epidemiological research. Findings of legal causation may contribute to popular
      perceptions that pertussis vaccine is a dangerous biological product. By
      providing compensation for these claimants, however, the NVICP may reduce the
      number of successful civil suits and thus protect the nation's vaccine supply.

PMID- 9635376
TI  - Long-term cytokine alterations following allogeneic blood transfusion.
AB  - BACKGROUND: Allogeneic blood transfusion is associated with an increased risk of
      infection and higher cancer recurrence rates. Previous research has shown that
      blood transfusion results in multiple immune effects, including cytokine
      alterations. The purpose of this study was to measure the long term kinetics of
      splenocyte cytokine production in transfused mice. METHODS: Balb/c mice received
      either syngeneic transfusion (Syn-BT) or allogeneic transfusion (Allo-BT) from
      C3H-HeN mice. Splenocyte production of IL-2, IL-6, IL-10, and IFN-gamma was
      quantitated by ELISA on post-transfusion days 5, 10, 21, and 30. RESULTS: Both
      Allo-BT and Syn-BT produced significant alterations in cytokine production, but
      Allo-BT produced the most dramatic and enduring effects as summarized: IL-2:
      Production of IL-2 was suppressed at day 5, (p < 0.0001), but then rose, peaking
      at day 21, 30% greater than control values (p < 0.05). IL-6: Allo-BT mice showed
      suppression of IL-6 throughout the study period (p < 0.005 vs controls, each time
      point). IL-10: A 5-fold increase in IL-10 production was seen at day 5 after Allo
      BT (p < 0.0001 vs control). Production of IL-10 was suppressed at days 10 and 21
      (p < 0.001), but returned to control levels by day 30, gamma-IFN: At day 5 post
      Allo-BT, gamma-IFN was 4 x greater than controls (p < 0.0001). Gamma-IFN
      production was suppressed at day 10, but then rose at days 21 and 30 to nearly 3
      x control levels (p < 0.0001). CONCLUSION: Allo-BT produced multiple cytokine
      alterations that were of prolonged duration. These results provide a theoretic
      explanation for the multiple, long-term immunomodulating effects seen in patients
      who have received transfusions.

PMID- 9635378
TI  - "Anything can happen" day.

PMID- 9635379
TI  - A public health perspective on optometry-ophthalmology relations.

PMID- 9635380
TI  - Traditional versus computer-assisted refraction: "which is better?".

PMID- 9635381
TI  - Multiple sclerosis, the great masquerader: an atypical ocular presentation.
AB  - BACKGROUND: Multiple sclerosis (MS) is the most common chronic disease of the
      central nervous system and is pleomorphic in it presentations. The optic pathways
      are frequently involved, and the classic ocular abnormality is optic neuritis.
      METHODS: A case is presented of a 23-year-old woman in whom optic neuropathy
      developed and multiple sclerosis was diagnosed by neuroradioimaging, in spite of
      her lack of awareness of vision loss. RESULTS: The demyelinating lesions in MS
      may develop anywhere in the visual system and produce a variety of visual
      defects. Magnetic resonance imaging (MRI) is the most sensitive method for
      demonstrating these lesions. CONCLUSION: The cause of MS is unknown, but current
      opinion holds that autoimmunity--perhaps induced by viral infection--is likely to
      be implicated in its etiopathogenesis. Currently, no method for prevention of MS
      is known.

PMID- 9635382
TI  - Comparison of diagnostic performance and fixation control of two automated
      perimeters.
AB  - BACKGROUND: The Humphrey perimeter and its Statpac (analysis programs have been
      widely used and studied. Another statistical analysis program, FieldView, is used
      with the Dicon perimeter. The purpose of this study was to compare the diagnostic
      performance of the two perimeters and their statistical analysis packages.
      METHODS: Twenty-three normal subjects (age range, 27 to 83 years) and 31 patients
      with glaucoma or cerebrovascular disease (age range, 28 to 87 years) experienced
      in automated perimetry were examined using the Dicon and the Humphrey perimeters.
      RESULTS: The total number of significant points identified on the Humphrey total
      deviation probability maps was in close agreement with statistical expectations,
      while the Dicon total deviation probability maps yielded significantly more false
      positive defects than expected for normals. Fixation loss ratios were almost
      twice as high with the Dicon perimeter (mean, 16%) as compared with the Humphrey
      perimeter (mean, 9%). The Humphrey perimeter was more reliable than the Dicon in
      measuring the defect depth of the physiological blind spot. CONCLUSION: The Dicon
      perimeter appears to yield excessive false-positive findings in normal subjects,
      resulting in poor sensitivity/specificity combinations, while at the same time
      failing to properly measure defect depth in scotomas.

PMID- 9635383
TI  - Multiple evanescent white dot syndrome.
AB  - BACKGROUND: Multiple evanescent white dot syndrome is a benign, rare, acute,
      usually unilateral disease that primarily affects young women. Retinal findings
      can include white dots at the level of the retinal pigment epithelium, optic
      nerve head swelling, an enlarged blind spot, and paracentral and central
      scotomas. Visual loss can be significant early on, but almost always returns to
      normal. The cause is unknown. CASE REPORT: A case of a 32-year-old woman with
      multiple evanescent white dot syndrome is presented and reviewed. The
      progression, symptoms, and differential diagnosis of multiple evanescent white
      dot syndrome are reviewed. CONCLUSION: The diagnosis of multiple evanescent white
      dot syndrome should be considered in young patients who manifest acute unilateral
      vision loss or photopsia. This is particularly important if there is unilateral
      disk swelling and blind-spot enlargement.

PMID- 9635384
TI  - Orbital pseudotumor: case report and overview.
AB  - BACKGROUND: The most common cause of a sudden onset of painful proptosis with
      diplopia in an otherwise healthy adult is orbital pseudotumor. However, there are
      other conditions that mimic this presentation and must be ruled out with
      laboratory testing and imaging studies. CASE REPORT: A 41-year-old Hawaiian man
      sought treatment for an acute, progressive, painful, left ophthalmoplegia without
      exophthalmos. During the next week, a loss of accommodation and associated
      pupillary reaction, decreased visual acuity, color vision deficits, and a
      paracentral scotoma developed. CT and MRI revealed a mass in the orbital apex.
      All systemic findings were negative, and high-dose systemic steroid therapy was
      initiated. Symptoms resolved within hours of the first dose, and signs were
      completely absent 1 month later. Follow-up MRI revealed complete absence of the
      previously noted mass. CONCLUSION: This is an atypical case of orbital
      pseudotumor, since there was no exophthalmos. It was diagnosed by clinical
      presentation, laboratory and imaging studies, and response to therapy.

PMID- 9635385
TI  - Nodular scleritis: case report involving immunosuppressive therapy.
AB  - BACKGROUND: Scleritis is a chronic inflammation of the scleral coat of the eye.
      Although the clinical manifestations of scleritis can follow a benign clinical
      course, the more serious forms may lead to vision loss and even enucleation of
      the eye. METHODS: A case is presented of a 57-year-old woman with a diagnosis of
      nodular scleritis and attendant ocular manifestations. RESULTS: Scleritis affects
      females slightly more frequently than males, and is most commonly found in
      patients who are 40 to 60 years of age. Patients who are symptomatic in only one
      eye typically have bilateral involvement within 5 years. More importantly, 50% of
      patients with scleritis have an underlying systemic disorder, which makes a
      detailed medical history and complete physical examination a crucial part of the
      treatment regimen. CONCLUSION: Recognizing the disease and determining the
      possible underlying systemic etiologies as early as possible will elucidate the
      appropriate treatment options and help suppress the potentially devastating
      effects of scleritis.

PMID- 9635387
TI  - Pitfalls in industrial drug screening.
AB  - Physicians need to establish a protocol for drug testing. Drug testing is, by its
      nature, often adversarial. Despite the confusing lack of standardized methods for
      handling positive and negative industrial drug tests, both pre-employment and
      random, physicians must be methodical in adhering to basic principles of privacy
      and careful in the interpretation of positive results. Errors in handling drug
      testing have and will continue to lead to avoidable lawsuits.

PMID- 9635386
TI  - Comparison of insulin regimens and administration modalities in pregnancy
      complicated by diabetes.
AB  - PURPOSE: To compare insulin administration using premixed insulin (70% NPH/30%
      Regular) by an injectable pen with traditional self-mixed insulin administered by
      syringe. METHODS: In this study, 93 women were enrolled into four groups: 1) self
      mixed/syringe, 2) premixed/syringe, 3) self-mixed/pen, and 4) premixed/pen.
      RESULTS: Women in the premixed pen group had significantly less cesarean
      deliveries for failure to progress in labor and a decrease (not significant) in
      postpartum infection and infant macrosomia. Patients felt premixed insulin
      administered by the pen was easier to use. No significant differences were noted
      in glucose control, compliance among the four groups, or cost. CONCLUSION:
      Premixed insulin administration via the pen is safe, effective and no more costly
      than traditional treatment for pregnant diabetic women.

PMID- 9635388
TI  - [Transcription factors and cell differentiation: roles of STAT proteins in
      Dictyostelium].

PMID- 9635389
TI  - [Pulmonary surfactant proteins: structure, function, pathophysiology].

PMID- 9635390
TI  - [Herpes simplex virus type 1-gene: functions and gene therapy].

PMID- 9635391
TI  - [Recent development of C-terminal sequence analysis of proteins].

PMID- 9635392
TI  - [Microbial endoglycosidases and their application: application of
      endoglycosidases which can liberate and transfer sugar].

PMID- 9635393
TI  - [Pathological changes of structure in the brain of Alzheimer's disease].

PMID- 9635394
TI  - [Preservation of mice strains and databases].

PMID- 9635395
TI  - [Live stock database].

PMID- 9635396
TI  - [A report from the Protein Data Bank].

PMID- 9635397
TI  - [Review of pH measurement (5): pH measurement a la carte].

PMID- 9635399
TI  - Evolution and homology of the nervous system: cross-phylum rescues of otd/Otx
      genes.

PMID- 9635400
TI  - Update CBP/p300 transgenic mice.

PMID- 9635401
TI  - Wasted by an elongation factor.

PMID- 9635402
TI  - Studies of populations and genetic diseases: mixing it up. Inherited disorders
      and their genes in different European populations, Acquafredda di Maratea, Italy,
      6-11 February 1998.

PMID- 9635403
TI  - Variations on the theme of genomics. Functional genomics: from identifying
      proteins to faster drug discovery, Westin City Center Hotel, Washington, DC, USA,
      10-11 March 1998.

PMID- 9635404
TI  - LCMV cDNA formation: which reverse transcriptase is responsible?

PMID- 9635405
TI  - The retinoblastoma gene family: cousins with overlapping interests.
AB  - The retinoblastoma tumor suppressor gene (RB1) and its relatives, p107 and p130,
      encode a family of proteins that share several properties, including the capacity
      to regulate E2F-dependent transcription and inhibit cell-cycle progression.
      Although RB1 inactivation is widely implicated in human cancer, the growth
      regulatory functions of p107 and p130, and the functional relationships within
      the gene family, are emerging only recently. Here we review studies of RB1 gene
      family function, with emphasis on in vivo experiments that explore shared and
      distinct functions within this family.

PMID- 9635406
TI  - Limbs are moving: where are they going?
AB  - The past decade has witnessed many changes in the way in which biologists study
      vertebrate development. Like curious children, we have progressed from merely
      watching and playing with our toys to the more exciting activity of taking them
      apart. This progression is mainly due to the application of a number of new
      techniques that allow us not only to ablate gene function, but also to induce
      gene activity inappropriately in time and space. Through the use of these
      techniques we can now disassemble our 'toys' and begin to understand how the
      pieces fit together and, thus, we are beginning to understand how the vertebrate
      embryo develops. Additionally, the analysis and comparison of limb development in
      diverse species has provided much insight into the evolutionary mechanisms
      through which changes in developmental pathways have led to the extraordinary
      diversity of limbs.

PMID- 9635407
TI  - Combinatorial control in ubiquitin-dependent proteolysis: don't Skp the F-box
      hypothesis.
AB  - The ubiquitin-dependent proteolytic pathway targets many key regulatory proteins
      for rapid intracellular degradation. Specificity in protein ubiquitination
      derives from E3 ubiquitin protein ligases, which recognize substrate proteins.
      Recently, analysis of the E3s that regulate cell division has revealed common
      themes in structure and function. One particularly versatile class of E3s,
      referred to as Skp1p-Cdc53p-F-box protein (SCF) complexes, utilizes substrate
      specific adaptor subunits called F-box proteins to recruit various substrates to
      a core ubiquitination complex. A vast array of F-box proteins have been revealed
      by genome sequencing projects, and the early returns from genetic analysis in
      several organisms promise that F-box proteins will participate in the regulation
      of many processes, including cell division, transcription, signal transduction
      and development.

PMID- 9635408
TI  - A simple mechanism for the avoidance of entanglement during chromosome
      replication.
AB  - The interphase nucleus of the human eukaryotic cell, before DNA replication,
      contains 46 linear DNA molecules, each of the order of centimeters in length, in
      a spherical nucleus with a diameter of 3-10 microns. How does the cell avoid
      topological entanglements between the 92 linear DNA molecules following
      replication? A model of chromosome replication is introduced, based on the
      assumption of the existence of a physical linkage between diverging growing forks
      during eukaryotic chromosome replication. This basic model is shown to be
      sufficient for the avoidance of DNA duplex entanglements during DNA replication.
      The model also suggests structural characteristics of chromosomes at various
      points in the cell cycle and provides a possible partial mechanism for chromosome
      condensation at the end of replication.

PMID- 9635409
TI  - Protein annotation: detective work for function prediction.

PMID- 9635410
TI  - Protection against carbon tetrachloride hepatotoxicity by oleanolic acid is not
      mediated through metallothionein.
AB  - Oleanolic acid is a triterpenoid compound that has been shown to protect against
      liver injury produced by some hepatotoxicants. This study was designed to
      characterize the protective effects of oleanolic acid on carbon tetrachloride
      induced hepatotoxicity, and the role of metallothionein in the protection.
      Oleanolic acid pretreatment (100-400 micromol/kg, s.c.) protected Sprague-Dawley
      rats and mice from carbon tetrachloride-induced liver injury in a dose- and time
      dependent manner, as evidenced by serum alanine aminotransferase and sorbitol
      dehydrogenase activities, as well as by histopathology. The protection against
      carbon tetrachloride hepatotoxicity was not evident until animals were pretreated
      with oleanolic acid 12 h, and lasted for 72 h after a single injection. This
      suggests that the protection might be due to induction of some adaptive
      mechanisms. Metallothionein (MT), an acute-phase protein proposed to decrease
      carbon tetrachloride-induced liver injury, was dramatically induced following
      oleanolic acid treatment. To examine whether oleanolic acid protection is
      mediated through MT, MT-I and II knock-out (MT-null) mice were utilized.
      Oleanolic acid pretreatment increased MT levels in control mice (20-fold), but
      not in MT-null mice, however, it protected equally against carbon tetrachloride
      induced hepatotoxicity in both control and MT-null mice. These data indicate that
      oleanolic acid is effective in protecting rats and mice from the hepatotoxicity
      produced by carbon tetrachloride, and the protection is not mediated through
      induction of MT.

PMID- 9635411
TI  - Alteration of acetohexamide reductase activities in kidney microsomes and cytosol
      of cadmium-treated rats.
AB  - We examined the alteration of acetohexamide reductase activities in kidney
      microsomes and cytosol of cadmium (Cd)-treated rats. Acetohexamide reductase
      activity in kidney microsomes of male rats was markedly decreased by treatment
      with Cd at a dose of 1.23 mg/kg body weight. However, the decreased enzyme
      activity was completely restored by repeated treatment with testosterone
      propionate. Therefore, it is reasonable to assume that the treatment with Cd
      indirectly affect the androgen-dependent acetohexamide reductase activity in
      kidney microsomes of male rats, possibly by depressing androgen production. In
      the case of female rats, unlike male rats, the microsomal enzyme activity was
      little detectable, and was unaffected by the treatment with Cd. Furthermore, Cd
      treatment had no significant effect on acetohexamide reductase activity in kidney
      cytosol of male or female rats.

PMID- 9635412
TI  - Modification of the rate of aging of diisopropylfluorophosphate-inhibited
      neuropathy target esterase of hen brain.
AB  - This study was aimed to investigate the possibility of modifying the rate of
      aging of diisopropylfluorophosphate-inhibited neuropathy target esterase (NTE) of
      hen brain. This reaction on NTE occurs with a half-time of 7.4 min. Atropine was
      effective in decreasing the rate of aging on DFP-inhibited NTE and this effect
      was time- and concentration-dependent. Atropine was also a weak but progressive
      inhibitor of NTE activity (I50 = 80 mM) and this reaction appears to be
      reversible at lower atropine concentrations. Among compounds containing oxime
      functional groups only OPAB, having longer methylene chain and being more
      lipophylic than other oximes usually used in acetylcholinesterase (AChE)
      reactivation studies, was effective in decreasing the rate of aging on DFP
      inhibited NTE. However, when atropine and oximes were used together we have
      obtained a potentiating and/or synergistic effect which was most significant with
      combination of atropine and TMB-4 giving up to a 15-fold decrease in the rate of
      aging reaction. The efficacy of this particular combination was concentration
      dependent. We have also discussed similarities and differences in aging reaction
      occurring on NTE and AChE.

PMID- 9635413
TI  - Melatonin reduces paraquat-induced genotoxicity in mice.
AB  - The protection afforded by melatonin against paraquat-induced genotoxicity in
      both bone marrow and peripheral blood cells of mice was tested using micronuclei
      as an index of induced chromosomal damage. Melatonin (2 mg/kg) or an equal volume
      of saline was injected i.p. into mice 30 min prior to the i.p. administration of
      paraquat (two injections of 15 mg/kg; the paraquat injections were given with a
      24 h interval) and thereafter at 6 h intervals to the conclusion of the study (72
      h). Using fluorescence microscopy, the number of micronuclei in polychromatic
      erythrocytes (MN-PCE) per 2000 PCE (1000 PCE/slide) per mouse was counted both in
      blood and bone marrow, and the ratio of PCE to normochromatic erythrocytes (NCE)
      (PCE/NCE) was calculated. Paraquat treatment increased the number of MN-PCE at
      24, 48, and 72 h, both in peripheral blood and bone marrow cells, while no
      differences were observed in the PCE/NCE ratio. Melatonin inhibited the paraquat
      induced increase in MN-PCE by more than 50% at 48 and 72h. Paraquat toxicity is
      believed to be due to free radical generation. Since melatonin is known to be an
      efficient free radical scavenger, it is concluded that melatonin's protection
      against paraquat-induced genotoxicity is mediated, at least in part, by its free
      radical scavenging activity.

PMID- 9635414
TI  - Simple spectrophotometric analysis of passive and active ear cutaneous
      anaphylaxis in the mouse.
AB  - Homologous passive cutaneous anaphylaxis (PCA) and active cutaneous anaphylaxis
      (ACA) to ovalbumin and DNP-hapten were studied in the ears of female BALB/c mice
      by means of assessing Evans blue dye leakage. For the quantitative evaluation of
      PCA and ACA, a hand-held spectrophotometer and the conventional colorimetric
      method were used to detect the amount of extravasated dye. The value of deltaE*ab
      (a numerical expression of color) obtained with the hand-held spectrophotometer
      and the amount of extravasated dye showed a good correlation. In the mouse ear,
      the sensitivity of PCA reaction was comparable to that of PCA in the rat, and
      deltaE*ab in the PCA and ACA reactions correlated well with the dilutions of sera
      and of the antigen, respectively. Thus, using a hand-held spectrophotometer is a
      simple, quantitative and sensitive method for ascertaining the extent of
      immediate-type hypersensitivity in the mouse.

PMID- 9635415
TI  - Lack of histological cerebellar changes in Wistar rats given pulegone for 28
      days. Comparison of immersion and perfusion tissue fixation.
AB  - Pulegone was given orally by gavage to groups of 28 SPF Wistar rats at dosage
      levels of 0 or 160 mg/kg body weight per day for 28 days. Clinically treated
      animals showed slackness, depression, decreased food consumption, and body
      weight. The loss of body weight was accompanied by a marked decrease in plasma
      creatinine. In contrast to earlier results, this study did not reveal occurrence
      of cyst-like spaces in the white matter of cerebellum using either perfusion or
      immersion tissue fixation techniques. Pulegone increased plasma alkaline
      phosphatase and relative liver weight indicating an adverse effect on the liver.

PMID- 9635416
TI  - Oxidation of 1,3-butadiene to (R)- and (S)-butadiene monoxide by purified
      recombinant cytochrome P450 2E1 from rabbit, rat and human.
AB  - 1,3-Butadiene (BD) is a gas used widely in the rubber and plastics industry as an
      intermediate in production processes and has been detected in automobile exhaust
      and cigarette smoke. BD requires metabolic activation to exert toxicity and has
      been shown to be carcinogenic in rodents. IARC has classified BD as a group 2A
      (probably carcinogenic to humans) carcinogen. The initial oxidation of BD to
      butadiene monoxide (BMO) occurs primarily via cytochrome P450 2E1 and two
      stereoisomers of BMO (R and S) can be formed. (R) and (S)-BMO are metabolized
      differently and demonstrate markedly different toxicities in isolated rat
      hepatocytes. This work examined the generation of (R) and (S)-BMO from BD by
      cytochrome P450 2E1 from rabbit, rat and human. BMO level was measured by GC-MS
      analysis and enantiomeric composition was determined by GC-FID. The greatest rate
      of formation of BMO from BD was obtained with rabbit cytochrome P4502E1 followed
      by human and then by rat. Enantiomeric distribution of R and S-BMO produced by
      the three species demonstrated no significant differences.

PMID- 9635418
TI  - Preventive effect of gamma-glutamylcysteinylethyl ester on carbon tetrachloride
      induced hepatic triglyceride accumulation in mice.
AB  - The effect of gamma-glutamylcysteinylethyl ester (gamma-GCE), which is a
      precursor of reduced glutathione (GSH), on carbon tetrachloride (CCl4)-induced
      hepatic triglyceride (TG) accumulation in mice was investigated in comparison
      with that of GSH. Administration of gamma-GCE (160 micromol/kg), but not GSH (160
      micromol/kg), to mice at 3 h after CCl4 injection (1 ml/kg, i.p.) significantly
      attenuated an increase in hepatic TG concentration at 6, 12, and 24 h after the
      CCl4 injection. A decrease in hepatic GSH concentration after the CCl4 injection
      was significantly diminished by the gamma-GCE administration, but not by the GSH
      administration. The correlation coefficient between hepatic TG concentration and
      hepatic GSH concentration was -0.627 (P < 0.001) when the results of all mice
      were grouped together. These results indicate that gamma-GCE can attenuate CCl4
      induced hepatic TG accumulation in mice through the maintenance of hepatic GSH
      level.

PMID- 9635417
TI  - Histopathological study in B6C3F1 mice chronically exposed by inhalation to
      glutaraldehyde.
AB  - Glutaraldehyde vapors are irritating for the skin, eyes, nose and lungs;
      respiratory symptoms and headaches have been described among workers exposed to
      low concentrations of glutaraldehyde far below to 190 ppb. This study was
      initiated to determine the chronic effects in mice of inhaled glutaraldehyde
      vapors. B6C3F1 mice were exposed using whole-body inhalation chambers, 6 h/day, 5
      days/week, for 52 and 78 weeks to 100 ppb, or to filtered air (controls). In
      nasal passages at the level of the vestibule, hyperplasia of the squamous
      epithelium lining of the dorsal wall and lateral aspect of the atrioturbinate was
      observed in a greater number of exposed females than in controls. Epidermal
      erosion and ulceration as well as squamous and inflammatory exfoliation were also
      seen in the nasal lumens. All these changes were dependent on the length of
      glutaraldehyde exposure. The present data suggest that glutaraldehyde long term
      exposure only led to changes in nasal passages of female mice but did not induce
      mortality and/or tumors in nasal passages, in all mice. These results, along with
      the previous subchronic inhalation study of Gross et al., 1994, demonstrates that
      in a long term study, chronic glutaraldehyde exposure close to the current
      threshold limit values induced lesions at the more anterior part of the nasal
      passages in mice and that they likely result from an irritation mechanism (antero
      posterior gradient).

PMID- 9635419
TI  - The fruit fly: a model organism to study the genetics of alcohol abuse and
      addiction?

PMID- 9635420
TI  - Drosophila ring canal growth requires Src and Tec kinases.

PMID- 9635421
TI  - Why the rat-1 fibroblast should replace the SCN as the in vitro model of choice.

PMID- 9635422
TI  - Myogenesis: a view from Drosophila.

PMID- 9635423
TI  - A serum shock induces circadian gene expression in mammalian tissue culture
      cells.
AB  - The treatment of cultured rat-1 fibroblasts or H35 hepatoma cells with high
      concentrations of serum induces the circadian expression of various genes whose
      transcription also oscillates in living animals. Oscillating genes include rper1
      and rper2 (rat homologs of the Drosophila clock gene period), and the genes
      encoding the transcription factors Rev-Erb alpha, DBP, and TEF. In rat-1
      fibroblasts, up to three consecutive daily oscillations with an average period
      length of 22.5 hr could be recorded. The temporal sequence of the various mRNA
      accumulation cycles is the same in cultured cells and in vivo. The serum shock of
      rat-1 fibroblasts also results in a transient stimulation of c-fos and rper
      expression and thus mimics light-induced immediate-early gene expression in the
      suprachiasmatic nucleus.

PMID- 9635424
TI  - Expanded polyglutamine protein forms nuclear inclusions and causes neural
      degeneration in Drosophila.
AB  - Spinocerebellar ataxia type 3 (SCA3/MJD) is one of at least eight human
      neurodegenerative diseases caused by glutamine-repeat expansion. We have
      recreated glutamine-repeat disease in Drosophila using a segment of the SCA3/MJD
      protein. Targeted expression of the protein with an expanded polyglutamine repeat
      led to nuclear inclusion (NI) formation and late-onset cell degeneration.
      Differential sensitivity to the mutant transgene was observed among different
      cell types, with neurons being particularly susceptible; NI formation alone was
      not sufficient for degeneration. The viral antiapoptotic gene P35 mitigated
      polyglutamine-induced degeneration in vivo. Our results demonstrate that cellular
      mechanisms of human glutamine-repeat disease are conserved in invertebrates. This
      fly model will aid in identifying additional factors that modulate
      neurodegeneration.

PMID- 9635425
TI  - The C. elegans cell corpse engulfment gene ced-7 encodes a protein similar to ABC
      transporters.
AB  - The C. elegans gene ced-7 functions in the engulfment of cell corpses during
      programmed cell death. We report that the CED-7 protein has sequence similarity
      to ABC transporters, is broadly expressed during embryogenesis, and is localized
      to the plasma membrane. Mosaic analysis revealed that ced-7 functions in both
      dying cells and engulfing cells during the engulfment process. We propose that
      CED-7 functions to translocate molecules that mediate homotypic adhesion between
      the cell surfaces of the dying and engulfing cells. Like CED-7, the mammalian ABC
      transporter ABC1 has been implicated in the engulfment of cell corpses,
      suggesting that CED-7 and ABC1 may be functionally similar and that the molecular
      mechanism underlying cell corpse engulfment during programmed cell death may be
      conserved from nematodes to mammals.

PMID- 9635426
TI  - Candidate adaptor protein CED-6 promotes the engulfment of apoptotic cells in C.
      elegans.
AB  - The rapid engulfment (phagocytosis) of cells undergoing programmed cell death
      (apoptosis) is a fundamental biological process that is not well understood. Here
      we report the cloning and functional characterization of ced-6, a gene
      specifically required for the engulfment of apoptotic cells in the nematode C.
      elegans. The CED-6 protein contains a phosphotyrosine binding domain at its N
      terminus and a proline/serine-rich region in its C-terminal half. Genetic mosaic
      analysis demonstrates that ced-6 acts within engulfing cells. We also show that
      ced-6 can promote the engulfment of cells at both early and late stages of
      apoptosis. Our data suggest that CED-6 is an adaptor molecule acting in a signal
      transduction pathway that specifically mediates the recognition and engulfment of
      apoptotic cells.

PMID- 9635427
TI  - Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a
      nuclear-encoded mitochondrial metalloprotease.
AB  - Hereditary spastic paraplegia (HSP) is characterized by progressive weakness and
      spasticity of the lower limbs due to degeneration of corticospinal axons. We
      found that patients from a chromosome 16q24.3-linked HSP family are homozygous
      for a 9.5 kb deletion involving a gene encoding a novel protein, named
      Paraplegin. Two additional Paraplegin mutations, both resulting in a frameshift,
      were found in a complicated and in a pure form of HSP. Paraplegin is highly
      homologous to the yeast mitochondrial ATPases, AFG3, RCA1, and YME1, which have
      both proteolytic and chaperon-like activities at the inner mitochondrial
      membrane. Immunofluorescence analysis and import experiments showed that
      Paraplegin localizes to mitochondria. Analysis of muscle biopsies from two
      patients carrying Paraplegin mutations showed typical signs of mitochondrial
      OXPHOS defects, thus suggesting a mechanism for neurodegeneration in HSP-type
      disorders.

PMID- 9635428
TI  - The forkhead/winged helix gene Mf1 is disrupted in the pleiotropic mouse mutation
      congenital hydrocephalus.
AB  - Mf1 encodes a forkhead/winged helix transcription factor expressed in many
      embryonic tissues, including prechondrogenic mesenchyme, periocular mesenchyme,
      meninges, endothelial cells, and kidney. Homozygous null Mf1lacZ mice die at
      birth with hydrocephalus, eye defects, and multiple skeletal abnormalities
      identical to those of the classical mutant, congenital hydrocephalus. We show
      that congenital hydrocephalus involves a point mutation in Mf1, generating a
      truncated protein lacking the DNA-binding domain. Mesenchyme cells from Mf1lacZ
      embryos differentiate poorly into cartilage in micromass culture and do not
      respond to added BMP2 and TGFbeta1. The differentiation of arachnoid cells in the
      mutant meninges is also abnormal. The human Mf1 homolog FREAC3 is a candidate
      gene for ocular dysgenesis and glaucoma mapping to chromosome 6p25-pter, and
      deletions of this region are associated with multiple developmental disorders,
      including hydrocephaly and eye defects.

PMID- 9635429
TI  - Ethanol intoxication in Drosophila: Genetic and pharmacological evidence for
      regulation by the cAMP signaling pathway.
AB  - Upon exposure to ethanol, Drosophila display behaviors that are similar to
      ethanol intoxication in rodents and humans. Using an inebriometer to measure
      ethanol-induced loss of postural control, we identified cheapdate, a mutant with
      enhanced sensitivity to ethanol. Genetic and molecular analyses revealed that
      cheapdate is an allele of the memory mutant amnesiac. amnesiac has been
      postulated to encode a neuropeptide that activates the cAMP pathway. Consistent
      with this, we find that enhanced ethanol sensitivity of cheapdate can be reversed
      by treatment with agents that increase cAMP levels or PKA activity. Conversely,
      genetic or pharmacological reduction in PKA activity results in increased
      sensitivity to ethanol. Taken together, our results provide functional evidence
      for the involvement of the cAMP signal transduction pathway in the behavioral
      response to intoxicating levels of ethanol.

PMID- 9635430
TI  - The preprotein translocation channel of the outer membrane of mitochondria.
AB  - The preprotein translocase of the outer membrane of mitochondria (TOM complex)
      facilitates the recognition, insertion, and translocation of nuclear-encoded
      mitochondrial preproteins. We have purified the TOM complex from Neurospora
      crassa and analyzed its composition and functional properties. The TOM complex
      contains a cation-selective high-conductance channel. Upon reconstitution into
      liposomes, it mediates integration of proteins into and translocation across the
      lipid bilayer. TOM complex particles have a diameter of about 138 A, as revealed
      by electron microscopy and image analysis; they contain two or three centers of
      stain-filled openings, which we interpret as pores with an apparent diameter of
      about 20 A. We conclude that the structure reported here represents the protein
      conducting channel of the mitochondrial outer membrane.

PMID- 9635431
TI  - Dynamin undergoes a GTP-dependent conformational change causing vesiculation.
AB  - The dynamin family of GTPases is essential for receptor-mediated endocytosis and
      synaptic vesicle recycling, and it has recently been shown to play a role in
      vesicle formation from the trans-Golgi network. Dynamin is believed to assemble
      around the necks of clathrin-coated pits and assist in pinching vesicles from the
      plasma membrane. This role would make dynamin unique among GTPases in its ability
      to act as a mechanochemical enzyme. Data presented here demonstrate that purified
      recombinant dynamin binds to a lipid bilayer in a regular pattern to form helical
      tubes that constrict and vesiculate upon GTP addition. This suggests that dynamin
      alone is sufficient for the formation of constricted necks of coated pits and
      supports the hypothesis that dynamin is the force-generating molecule responsible
      for membrane fission.

PMID- 9635432
TI  - GBP, an inhibitor of GSK-3, is implicated in Xenopus development and oncogenesis.
AB  - Dorsal accumulation of beta-catenin in early Xenopus embryos is required for body
      axis formation. Recent evidence indicates that beta-catenin is dorsally
      stabilized by the localized inhibition of the kinase Xgsk-3, utilizing a novel
      Wnt ligand-independent mechanism. Using a two-hybrid screen, we identified GBP, a
      maternal Xgsk-3-binding protein that is homologous to a T cell protooncogene in
      three well-conserved domains. GBP inhibits in vivo phosphorylation by Xgsk-3, and
      ectopic GBP expression induces an axis by stabilizing beta-catenin within Xenopus
      embryos. Importantly, antisense oligonucleotide depletion of the maternal GBP
      mRNA demonstrates that GBP is required for the establishment of the dorsal
      ventral axis in Xenopus embryos. Our results define a family of GSK-3-binding
      proteins with roles in development and cell proliferation.

PMID- 9635433
TI  - Geminin, an inhibitor of DNA replication, is degraded during mitosis.
AB  - We describe a novel 25 kDa protein, geminin, which inhibits DNA replication and
      is degraded during the mitotic phase of the cell cycle. Geminin has a destruction
      box sequence and is ubiquitinated anaphase-promoting complex (APC) in vitro. In
      synchronized HeLa cells, geminin is absent during G1 phase, accumulates during S,
      G2, and M phases, and disappears at the time of the metaphase-anaphase
      transition. Geminin inhibits DNA replication by preventing the incorporation of
      MCM complex into prereplication complex (pre-RC). We propose that geminin
      inhibits DNA replication during S, G2, and M phases and that geminin destruction
      at the metaphase-anaphase transition permits replication in the succeeding cell
      cycle.

PMID- 9635434
TI  - Globin gene expression is reprogrammed in chimeras generated by injecting adult
      hematopoietic stem cells into mouse blastocysts.
AB  - To elucidate whether the differentiation capacity of hematopoietic stem cells
      (HSCs) is influenced by specific microenvironments, adult mouse bone marrow
      derived HSCs were injected into mouse blastocysts. Embryos developing from
      injected blastocysts contained donor-derived cells at various developmental
      stages, and progeny of the stem cells were detected in hematopoietic tissues.
      Thus, HSCs derived from an adult animal survive after injection into blastocysts
      and are able to participate in hematopoietic development. We further find that
      the erythroid progeny of transplanted adult HSCs express embryonic/fetal-type
      globin genes and, conversely, that embryonic and fetal progenitor cells
      transplanted into adult recipients transcribe the adult-type globin gene. Thus,
      the developmental potential of adult HSCs is evidently more plastic than
      previously thought, and the developmental stage of the hematopoietic
      microenvironment controls the developmental fate of transplanted progenitor
      cells.

PMID- 9635435
TI  - An ESP1/PDS1 complex regulates loss of sister chromatid cohesion at the metaphase
      to anaphase transition in yeast.
AB  - Cohesion between sister chromatids during G2 and M phases depends on the
      "cohesin" protein Scc1p (Mcd1p). Loss of cohesion at the metaphase to anaphase
      transition is accompanied by Scc1p's dissociation from chromatids, which depends
      on proteolysis of Pds1p mediated by a ubiquitin protein ligase called the
      anaphase promoting complex (APC). We show that destruction of Pds1p is the APC's
      sole role in triggering Scc1p's dissociation from chromatids and that Pds1p forms
      a stable complex with a 180 kDa protein called Esp1p, which is essential for the
      dissociation of Scc1p from sister chromatids and for their separation. We propose
      that the APC promotes sister separation not by destroying cohesins but instead by
      liberating the "sister-separating" Esp1 protein from its inhibitor Pds1p.

PMID- 9635436
TI  - The small GTP-binding protein RhoA regulates a delayed rectifier potassium
      channel.
AB  - Tyrosine kinases activated by G protein-coupled receptors can phosphorylate and
      thereby suppress the activity of the delayed rectifier potassium channel Kv1.2.
      Using a yeast two-hybrid screen, we identified the small GTP-binding protein RhoA
      as a necessary component in this process. Coimmunoprecipitation experiments
      confirmed that RhoA associates with Kv1.2. Electrophysiological analyses revealed
      that overexpression of RhoA markedly reduced the basal current generated by Kv1.2
      expressed in Xenopus oocytes. Furthermore, in 293 cells expressing Kv1.2 and ml
      muscarinic acetylcholine receptors, inactivating RhoA using C3 exoenzyme blocked
      the ability of ml receptors to suppress Kv1.2 current. Therefore, these results
      demonstrate that RhoA regulates Kv1.2 activity and is a central component in the
      mechanism of receptor-mediated tyrosine kinase-dependent suppression of Kv1.2.

PMID- 9635437
TI  - Histopathological, lymphoscintigraphical, and immunological changes in the
      inguinal lymph nodes of rhesus monkeys during the early course of infection with
      Brugia malayi.
AB  - The relationship of the early lymphatic pathophysiological alterations with those
      of tissue inflammatory and cellular responses in the inguinal lymph nodes of
      Brugia malayi-infected rhesus monkeys was examined. Each of five animals was
      inoculated subcutaneously in the right calf with 200 third stage larvae (L3) and
      5 weeks later, before the onset of patency [10 to 12 weeks postinoculation (PI)],
      their right inguinal nodes began to show signs of enlargement, becoming most
      prominent between weeks 10 to 16 PI. Histopathologically, the right nodes had
      eosinophilic lymphadenitis, lymphoid hyperplasia, and pronounced germinal
      centers. Lymphoscintigraphy using 99mTc-antimony trisulfide colloid showed
      pathophysiological alterations of the lymph flow rate in the right leg but not in
      the left leg at weeks 7 and 15 PI. In vitro blastogenesis to B. malayi antigens
      at week 10 PI showed the inguinal lymph node cells proliferated more vigorously
      than did peripheral blood cells early in infection. However, at week 24 PI both
      lymph node and peripheral blood cells proliferated to antigens. Flow cytometry
      showed an upregulation of HLA-DR+ lymphocytes in right lymph node cells from
      infected animals when compared to those from control animals. No changes in CD2,
      CD4, CD8, CD20, CD29, and CD45R cell numbers in lymph node of infected animals
      were seen when compared to control animals. Our results show that lymphatic
      pathology occurs early before the onset of patency, correlating with a marked
      tissue inflammatory and cellular responses of lymph node cells in B. malayi
      infected rhesus monkeys. The rhesus could be an extremely useful model for
      understanding the evolution of pathology and pathogenesis of the disease.

PMID- 9635438
TI  - Leishmania (Leishmania) amazonensis: purification and enzymatic characterization
      of a soluble serine oligopeptidase from promastigotes.
AB  - A soluble proteinase was purified 90-fold from extracts of promastigotes of
      Leishmania (Leishmania) amazonensis using a combination of ion-exchange
      chromatography in Q-Sepharose Fast Flow, gel filtration chromatography in
      Sephacryl HR S-200, and chromatofocusing. The enzyme appeared as a single band
      with an apparent molecular weight of 101 kDa by silver staining following SDS
      PAGE, under both reducing and nonreducing conditions. The proteinase has a pH
      optimum between 8.0 and 8.5 and an isoelectric point between 5.12 and 5.23,
      belongs to the serine proteinase class, and is inhibited by Mg2+, Ca2+, and K+.
      The primary specificity determined using synthetic substrates is for basic amino
      acids. The kinetic parameters for the Bz-L-Arg-Nam substrate are Km = 26 microM,
      kcat = 32 min(-1), and Ksi = 1270 microM (the proteinase showed inhibition by
      excess substrate). The enzyme does not hydrolyze casein, albumin, and gelatin or
      large peptides like the oxidized insulin B chain, but hydrolyzes small peptides
      like bradykinin and fragment 4-10 of the adrenocorticotropic hormone, at the
      carboxyl side of basic residues and aromatic residues preceding basic residues.
      The enzyme appears, thus, to be restricted in its action, cleaving only small
      peptide substrates, which characterizes the proteinase as an oligopeptidase. This
      is the first report of purification of a serine peptidase from Leishmania species
      and it increases the short list of known oligopeptidases.

PMID- 9635439
TI  - Leishmania: amastigotes synthesize conserved secretory acid phosphatases during
      human infection.
AB  - Leishmania donovani is the major causative agent of Old World human visceral
      leishmaniasis (VL). In vitro, both promastigotes and axenic amastigotes of L.
      donovani constitutively secrete soluble acid phosphatases (SAcPs), which contain
      conserved antigenic epitopes. These SAcPs are the most abundant and best
      characterized secretory proteins of this parasite. The aim of this study was to
      determine whether this enzyme was produced by intracellular amastigotes during
      the course of human infection. To that end, sera from acutely infected
      leishmaniasis patients were tested for anti-SAcP antibodies using L. donovani
      promastigote culture supernatants. Our results showed that VL patient sera from
      different endemic foci immunoprecipitated parasite SAcP enzyme activity. Further,
      these VL patient sera recognized the 110- and 130-kDa SAcPs in both Western blots
      and radioimmunoprecipitation assays. Results of tunicamycin experiments
      demonstrated that VL patient anti-SAcP antibodies were directed against the
      polypeptide backbone of the parasite SAcPs. In addition, both radiolabeled L.
      donovani SAcPs and native enzyme activities were immunoprecipitated by sera from
      patients with various forms of cutaneous leishmaniasis. Together, these studies
      demonstrate that Leishmania amastigotes produce SAcPs during the course of human
      infections.

PMID- 9635440
TI  - Fasciola hepatica: stage-specific expression of novel gene sequences as
      identified by differential display.
AB  - Differences in gene expression between adult and immature Fasciola hepatica
      (liver fluke) parasites isolated from the mammalian host were investigated using
      the technique of differential display. For any given primer combination used to
      produce these displays there were, on average, 22% apparently adult-specific and
      14% apparently immature-specific cDNA products able to be identified, consistent
      with a high degree of differential gene expression between these two parasite
      developmental stages. Several cDNA fragments specific to immature parasite RNA
      were isolated and cloned. An abundant 400- to 500-bp RNA species was identified
      on a Northern blot by hybridization to the cloned DD2 cDNA fragment and was
      determined to be expressed at levels at least 10-fold higher in immature
      parasites relative to adult parasites. mRNA transcripts corresponding to the
      remaining cDNA fragments (DD14, DD16, DISP10, and DISP2) were apparently
      expressed at levels below the sensitivity limits of Northern analysis, although
      differential expression of these transcripts was confirmed by reverse
      transcriptase PCR (RT-PCR). The identities or functional significance of each of
      the five differentially expressed cDNAs identified in this study is still unclear
      due to the lack of any significant sequence similarity to the entries currently
      held within sequence databases.

PMID- 9635441
TI  - Biomphalaria spp: identification of the intermediate snail hosts of Schistosoma
      mansoni by polymerase chain reaction amplification and restriction enzyme
      digestion of the ribosomal RNA gene intergenic spacer.
AB  - The intermediate hosts of S. mansoni in South America, B. glabrata, B.
      tenagophila, and B. straminea, were identified by restriction fragment length
      polymorphism (RFLP) analysis of the internal transcribed spacer region of the
      rRNA gene. The restriction patterns obtained with DdeI were the most informative
      of the eight enzymes that were tried. The RFLP profiles obtained using this
      enzyme are highly distinctive and exhibit low levels of intraspecific
      polymorphism even between specimens collected from diverse regions of Brazil,
      Argentine, Paraguay, and Uruguay. The method proved useful for the identification
      of DNA extracted from eggs, permitting species identification while preserving
      the living adult specimens for further studies.

PMID- 9635442
TI  - Trypanosoma cruzi 175-kDa protein tyrosine phosphorylation is associated with
      host cell invasion.
AB  - We examined the requirement of Tropanosoma cruzi protein tyrosine phosphorylation
      for parasite entry into mammalian cells and analyzed the profile of
      phosphorylated proteins in infective trypomastigotes. Treatment of metacyclic or
      tissue culture trypomastigotes with genistein, an inhibitor of protein tyrosine
      kinase activity, significantly inhibited invasion of cultured HeLa cells. A
      soluble factor, contained in HeLa cell extract and absent in the extract ot T.
      cruzi-resistant K562 cells, greatly enhanced phosphorylation levels of a 175-kDa
      protein (p175) in trypomastigotes. Genistein inhibited p175 tyrosine
      phosphorylation. P175 was undetectable in noninvasive epimastigotes. The
      phosphorylation-inducing activity of HeLa cell extract was abrogated by
      adsorption with metacyclic trypomastigotes but not with epimastigotes or when it
      was mixed with recombinant protein J18, which contains the entire peptide
      sequence of gp82, a metacyclic stage-specific surface glycoprotein implicated in
      target cell invasion. These data suggest that, in metacyclic trypomastigotes,
      gp82 is the signaling receptor that mediates protein tyrosine phosphorylation
      necessary for host cell invasion.

PMID- 9635443
TI  - Trichomonas vaginalis and Tritrichomonas foetus: expression of chitin at the cell
      surface.
AB  - The expression of chitin as a structural component of Trichomonas vaginalis and
      Tritrichomonas foetus was demonstrated by using enzymatic hydrolysis by
      recombinant (rec-) chitinase, chemical analysis, lectin, fluorescent Calcofluor
      and antibody binding, glycosidases of known specificity, high-performance liquid
      chromatography (HPLC), and flow cytometry. Chitinous structures were
      characterized by their insolubility in hot alkali and by releasing glucosamine on
      hydrolysis with 6 N HCl. N,N'-Diacetylchitobiose and N,N,'N''
      triacetylchitotriose were identified by HPLC as enzymatic hydrolysis products of
      the alkali-resistant polysaccharide. The location of chitin on the surface of T.
      vaginalis and T. foetus was inferred from the decreased reactivity with whole
      parasites of ligands such as Lycopersicon esculentum (TOL) and Solanum tuberosum
      lectins, fluorescent Calcofluor, and anti-chitin antibody, after cell treatment
      with rec-chitinase. Binding of [125I]TOL showed that, in T. vaginalis and T.
      foetus, the numbers of lectin receptors per cell were 4.2 x 10(5) and 3.0 x
      10(5), respectively. Binding of the lectin to the trichomonad surface was
      markedly decreased by treatment with rec-chitinase. TOL interaction with the
      parasites was not affected by N-acetyl-beta-D-glucosaminidase treatment, showing
      that the lectin receptors consisted of beta-linked GlcNAc polymers and not of
      terminal beta-linked GlcNAc residues.

PMID- 9635444
TI  - Efficacy of ivermectin against Strongyloides stercoralis infection in jirds
      (Meriones unguiculatus).
AB  - The activity and distribution of ivermectin (IVM), a broad spectrum anthelmintic
      for various nematodes and arthropods, was tested against Strongyloides
      stercoralis infection in the jird (Meriones unguiculatus.) The pattern of IVM
      concentration in the serum of jirds after either low- (200 microg/kg) or high
      dose (1000 microg/kg) treatment by intraperitoneal injection showed a typical
      single-peak profile with the maximum drug levels detected at 1 h followed by a
      rapid decline to undetectable values by 48 h posttreatment. With equivalent IVM
      doses, the serum levels in male jirds were significantly higher than those
      observed in female jirds at 1 and 12 h posttreatment (P < 0.05). Low-dose IVM
      treatment of either male or female jirds, in comparison with that of the
      respective control groups, produced no observable effect on the adult worm burden
      or the parasite fecundity. The curative dose for S. stercoralis in both sexes of
      animals was achieved when using the high dose of 1000 microg/kg of IVM. The area
      under the curve calculated from the serum-concentration profiles in males was
      significantly higher than that for females after the high-dose treatment of IVM
      (P < 0.05). By low-dose treatment, a significantly lower adult worm burden was
      observed in males compared with that in females (P < 0.05), and this difference
      correlated with the higher serum levels of IVM in male animals. The distribution
      of IVM in the jird after high-dose treatment was characterized by initial
      appearances at 1 h of maximum levels of the drug in the serum and intestinal
      content. The maximum level in the feces was reached at 12 h posttreatment and
      rapidly declined thereafter. The level in the intestinal tissue was comparatively
      much lower than that in the intestinal content and the feces. The half-life of
      IVM in the intestinal content (49.5 h) was longer than those in the serum, feces,
      and intestinal tissue (6.53-13.07 h). Analyses of the relationship between the
      peak serum IVM occurring at 1 h posttreatment and the adult worm recovery
      revealed that the minimal serum concentration associated with clearance of the
      adult worm from the jird was approximately 0.65 microg/ml. The jird-S.
      stercoralis model has not only made studies on various aspects of parasite
      biology possible, but also provided an in vivo system to examine the efficacy as
      well as the mode of action of IVM against this intestinal nematode.

PMID- 9635445
TI  - Ixodes scapularis: salivary kininase activity is a metallo dipeptidyl
      carboxypeptidase.
AB  - Saliva and salivary gland homogenates of Ixodes scapularis contain a dipeptidyl
      carboxypeptidase activity that accounts for the previously described salivary
      kininase activity of this tick. Reversed phase HPLC and laser desorption mass
      spectrography of the reaction products identified bradykinin fragment 1-7 and 1-5
      as being produced subsequent to incubation of purified salivary kininase with
      bradykinin. The activity was inhibited by captopril and EDTA and was activated by
      cobalt and manganese, a behavior similar to that displayed by angiotensin
      converting enzymes of vertebrate and invertebrate origins.

PMID- 9635446
TI  - Schistosoma mansoni: the varying occurrence of repetitive elements in different
      strains shows sex-specific polymorphisms.
AB  - The repetitive elements W1, W2, and D9 were shown before to be female specific in
      the Puerto Rican strain of Schistosoma mansoni. In the Liberian strain, however,
      W1 was detected in both sexes. Therefore, a strain- and sex-specific analysis of
      the presence of all three repetitive elements has been performed in different
      schistosome strains. For this analysis, W2 has been isolated and characterized,
      whereas W1 and D9 were already available. We demonstrate the presence of the W2
      element in both sexes in the Liberian strain, which coincides with W1.
      Furthermore, it is shown that elements W1 and W2, but not D9, can be found in
      both sexes of the majority of the other strains investigated. We even found an
      isolate of the Puerto Rican strain with W1 and W2 elements in females and males.
      This finding contradicts results reported in the literature that demonstrated
      that W1 and W2 are female specific for the Puerto Rican strain. The data of this
      study indicate sex-specific polymorphisms, probably associated with the sex
      chromosomes in schistosomes.

PMID- 9635447
TI  - Theileria annulata: the expression of two novel macroschizont antigens on the
      surface of infected mononuclear cells differs during in vitro attenuation of a
      virulent cell line.
AB  - The first part of this study of the biological mechanisms underlying attenuation
      of virulent Theileria annulata macroschizont-infected cell lines screened four
      pairs of T. annulata (Hisar) in vivo- and in vitro-derived macroschizont-infected
      cell lines (lines) and identified a single in vivo-derived line, which induced
      lethal tropical theileriosis. The other seven lines were relatively avirulent.
      Analysis of the clinical, hematological, and parasitological responses of cattle
      immunized with different passages of the virulent line after in vitro culture
      showed that it was partly attenuated by passage (p) 50 and avirulent by p130.
      Clones representing the three glucose phosphate isomerase (GPI) isotypes, which
      constituted the newly isolated virulent culture, were obtained from p3 by
      limiting dilution; p50 and p130 consisted of one isotype. The second part of the
      study raised monoclonal antibodies (MAbs) against macroschizont-infected cells,
      as reagents for detecting antigenic differences between virulent and avirulent
      parasites, and identified two MAbs that recognized the surface of infected cells
      as well as macroschizonts. MAb EU1 recognized an antigen expressed by all the
      lines tested, whether in vitro- or in vivo-derived, whether uncloned or cloned,
      and irrespective of extent of subpassage in culture. MAb EU106 recognized an
      antigen whose expression by the virulent line and its clones disappeared on
      passage in culture. This antigen was not expressed at all by the avirulent in
      vitro-derived line prepared with cells from the same calf. Both antigens were
      expressed by lines infected with other stocks of T. annulata, including two lines
      known to induce lethal disease. The different profiles of expression of the two
      novel antigens, recognized by MAbs EU1 and EU106, by the line undergoing
      attenuation suggest (1) that the two antigens interact differently with the
      bovine immune system; and (2) that there are two, very different, potential roles
      for these antibodies in the development of vaccines against T. annulata
      infections.

PMID- 9635448
TI  - Trichomonas vaginalis: in vitro phagocytosis of lactobacilli, vaginal epithelial
      cells, leukocytes, and erythrocytes.
AB  - This paper explores the interaction of two strains of Trichomonas vaginalis, of
      high and low virulence, with the cell types present in the microenvironment of
      the parasite during human infections. With the use of transmission and scanning
      electron microscopy the sequence of internalization by T. vaginalis of
      Doderlein's lactobacilli, and of vaginal epithelial cells, leukocytes, and
      erythrocytes was documented. Furthermore, the degradation of ingested material by
      colocalization of acid phosphatase activity in phagocytic vacuoles was
      demonstrated. Phagocytosis of all cell types analyzed was found in both strains
      studied, although the highly virulent strain internalized target cells more
      rapidly than the less virulent one. Ultrastructural evidence indicated that
      phagocytosis takes place through two distinct mechanisms, only one involving the
      formation of a phagocytic stoma, characteristic of professional phagocytes. T.
      vaginalis phagocytosis may be both an efficient means of obtaining nutrients for
      the parasite and a significant factor in the pathogenesis of trichomonal
      infections of the human genitourinary tract.

PMID- 9635449
TI  - Trypanosoma cruzi: a novel chemical class (nitrobenzofurans) active against
      infections of mice (Mus musculus).

PMID- 9635450
TI  - Anisakis simplex: mutational bursts in the reactive site centers of serine
      protease inhibitors from an ascarid nematode.

PMID- 9635451
TI  - Plasmodium falciparum: parasite typing by using a multicopy microsatellite
      marker, PfRRM.

PMID- 9635452
TI  - Genus-specific expression from the SL RNA promoter of Leishmania amazonensis.

PMID- 9635453
TI  - Incidence of frontal sinusitis following partial middle turbinectomy.
AB  - The role of partial middle turbinate resection as an adjunct to endoscopic sinus
      surgery is controversial. Recent literature suggests that middle turbinate
      resection may have a detrimental effect on the frontal sinus. A retrospective
      analysis of 155 consecutive patients undergoing partial middle turbinate
      resection utilizing the technique of the senior author (J.A.D.) for either
      sinusitis or nasal obstruction was conducted. The data reveal a low rate of
      frontal sinusitis following partial middle turbinectomy (10%). None of the
      patients undergoing partial middle turbinectomy for nasal obstruction developed
      frontal sinusitis postoperatively. No major complications were encountered.
      Frontal sinusitis following middle turbinectomy was often associated with
      preoperative comorbidity such as asthma, nasal polyps, severe disease score on
      computed tomography, or diseased middle turbinates. The authors conclude that
      partial middle turbinectomy for treatment of sinusitis and nasal obstruction has
      a low incidence of postoperative frontal sinusitis. Development of frontal
      sinusitis may be predictable on the basis of several comorbid factors.

PMID- 9635454
TI  - Biomechanics of arytenoid adduction surgery in an ex vivo canine model.
AB  - The biomechanics of arytenoid adduction surgery are not well understood. An
      excised canine larynx model was used to study the effects of variable suture
      tension on glottal configuration and on vocal fold tension (at the midfold and
      the vocal process). Arytenoid adduction both medializes the vocal fold and closes
      a posterior glottal chink. Vocal fold tension at the midfold did not vary
      significantly with suture tension. As suture tension increased to approximately
      100 g, vocal fold tension at the vocal process also increased. Beyond 100 g of
      suture tension, vocal fold tension at the vocal process did not increase. We
      conclude that the effects of suture tension on the resistance to lateral movement
      are different at the midfold compared to the vocal process. Procedures for
      surgical rehabilitation of vocal fold paralysis should address the biomechanical
      subunits of the larynx individually in order to achieve optimum results.

PMID- 9635455
TI  - Cervicomedullary compression: an unrecognized cause of vocal cord paralysis in
      rheumatoid arthritis.
AB  - Cervicomedullary compression (CMC) from traumatic, infectious, or congenital
      processes of the atlanto-axial joint is a known cause of vocal cord immobility.
      Cervicomedullary compression can also occur from destructive arthritic changes
      and inflammatory pannus formation at the occipito-atlanto-axial joint in patients
      with rheumatoid arthritis (RA). We present findings suggesting that CMC in
      patients with RA is an unrecognized cause of vocal cord immobility. Previously,
      vocal cord immobility in patients with RA has been assumed to be cricoarytenoid
      arthritis with joint fixation. We report 3 patients with RA and radiographically
      demonstrated CMC with vocal cord immobility. One patient had bilateral vocal cord
      immobility and airway obstruction; 2 patients had unilateral cord paralysis and
      contralateral paresis without airway compromise. All patients had myelopathy and
      neck pain in addition to brain stem symptoms. All patients underwent transoral
      transpharyngeal decompression of the anterior craniocervical junction with
      subsequent posterior fusion. These patients demonstrated full return of vocal
      cord function within 3 months of decompression. We propose that CMC is a cause of
      vocal cord paralysis in patients with RA that may go unrecognized without
      appropriate imaging studies of the skull base and physician awareness of symptoms
      of occipito-atlanto-axial subluxation and/or basilar invagination with brain stem
      compression. Our results demonstrate that CMC in RA is a potentially reversible
      cause of vocal cord paralysis.

PMID- 9635456
TI  - Microvascular lesions of the true vocal fold.
AB  - Microvascular lesions, also called varices or capillary ectasias, in contrast to
      vocal fold polyps with telangiectatic vessels, are relatively small lesions
      arising from the microcirculation of the vocal fold. Varices are most commonly
      seen in female professional vocalists and may be secondary to repetitive trauma,
      hormonal variations, or repeated inflammation. Microvascular lesions may either
      be asymptomatic or cause frank dysphonia by interrupting the normal vibratory
      pattern, mass, or closure of the vocal folds. They may also lead to vocal fold
      hemorrhage, scarring, or polyp formation. Laryngovideostroboscopy is the key in
      determining the functional significance of vocal fold varices. Management of
      patients with a varix includes medical therapy, speech therapy, and occasionally
      surgical vaporization. Indications for surgery are recurrent hemorrhage,
      enlargement of the varix, development of a mass in conjunction with the varix or
      hemorrhage, and unacceptable dysphonia after maximal medical and speech therapy
      due to a functionally significant varix.

PMID- 9635457
TI  - Assessment of vocal function using simultaneous aerodynamic and calibrated
      videostroboscopic measures.
AB  - Despite many attempts to model how vocal fold movements relate to the aerodynamic
      forces acting on them during phonation, there have been few simultaneous
      measurements of glottal area and transglottal air pressures and flows. A novel
      system is described that combines endoscopic measurement of glottal area with
      aerodynamic flow and pressure measures made during phonation. Results from bench
      top model tests and from one human subject are presented. For both tests, an
      aerodynamic model of airflow through a constriction was used to predict the area
      of the constriction (glottis), and these predictions were compared with
      endoscopic measurements. The results showed good correlation between predicted
      and observed areas; however, for small constrictions (<0.025 cm2), whether
      artificial or glottal, the errors in estimating areas with either optical or
      aerodynamic methods increase significantly. These results suggest that this
      measurement system has the potential to enhance the assessment of vocal function.

PMID- 9635458
TI  - Revision surgery for chronic otitis media: a learning experience. Report on 389
      cases with a long-term follow-up.
AB  - The objective of this study was to evaluate, during a long-term follow-up period,
      the results of revision surgery for chronic otitis media with or without
      cholesteatoma. Intact canal wall and canal wall down procedures were performed.
      The surgical history of every patient was assessed before the operation. A dry,
      relatively safe, and disease-free ear was created in 90% of the reoperated ears
      (N = 389). The recurrence rate of cholesteatoma was 5% for the total group.
      Reperforations of the tympanic membrane occurred in 10%, and persistent or
      recurrent otorrhea was present in 10% of cases. The functional hearing results
      were quite satisfactory. A residual air-bone gap of < or =30 dB was reached in
      70.3% of the cases after revision tympanoplasty only (N = 41). Revision
      mastoidectomy with revision tympanoplasty as a one-stage procedure led
      subsequently, in 76% of intact canal wall procedures (N = 113) and 55% of canal
      wall down procedures (N = 98), to a residual air-bone gap of < or =30 dB.

PMID- 9635459
TI  - Cochlear implantation in children with inner ear malformations.
AB  - We performed a case study and intervention study, with follow-up of 1 to 5 years,
      in 4 children with inner ear malformations who underwent implantation of a
      multichannel cochlear implant (Nucleus, Cochlear Corporation) at ages 3 to 12
      years. Malformations included a common cavity deformity, 2 incomplete partitions,
      and 1 case of isolated bilateral vestibular aqueduct enlargement. One child had a
      single-channel implant placed at 3 years of age, and this was exchanged for a 22
      channel implant at age 9. One child had her implant placed at age 4.5 years, but
      due to complications from a cerebrospinal fluid (CSF) leak had the initial
      implant removed and replaced at age 5 years during repair of the CSF leak.
      Intraoperative findings included a CSF leak at the time of surgery in 3 patients.
      One patient contracted bacterial meningitis 7 months postimplantation that was
      thought to be secondary to acute otitis media in the unoperated ear. Bilateral
      CSF leaks were noted in the middle ear by a lumbar puncture radionuclide and
      fluorescein dye study. Successful repair of the CSF leaks and reimplantation of
      the cochlear implant was carried out in this patient. Mapping and programming of
      the implant was found to be challenging in each of these patients. All patients
      demonstrated improved performance after implantation. Two patients demonstrated
      some open-set speech perception. One patient demonstrates improved use of
      temporal cues in a structured closed set. One patient has achieved no significant
      speech recognition at this time, but does have improved sound detection and
      awareness. Cochlear implantation in children with congenital inner ear
      abnormalities can be a successful method of rehabilitation. It should be
      recognized that the postoperative speech perception results may be highly
      variable among patients, and that intraoperative complications may occur.

PMID- 9635460
TI  - Upregulation of messenger RNA for inflammatory cytokines in middle ear mucosa in
      a rat model of acute otitis media.
AB  - A rat model for acute otitis media has been established and was used to delineate
      the temporal expression of messenger RNA for key inflammatory cytokines.
      Inoculation with live Streptococcus pneumoniae induced a rapid expression of
      tumor necrosis factor alpha (within 6 hours) followed by upregulation of message
      for interleukin (IL)-6 (peak at 12 to 24 hours, remaining elevated through 120
      hours) and IL-10 (peak at 24 hours). Inducible nitric oxide synthase message was
      also selectively increased following live bacterial inoculation (peak at 12 to 24
      hours). Although there was a detectable inflammatory response to killed bacteria,
      it was minimal, was of short duration, and preceded the peak for live bacteria;
      only expression of IL-6 was significantly increased in this group (peak at 12
      hours, remaining elevated through 72 hours). We interpret this to be due to an
      inflammatory response to bacterial products (such as lipopolysaccharide) in the
      heat-killed bacterial inoculum. The phosphate-buffered saline (PBS)-inoculated
      group exhibited a transient increase of IL-6 message, which indicates that this
      cytokine is a sensitive marker of the acute response to trauma. Otherwise, PBS
      invoked only a slight reaction in the mucosa with respect to the other
      inflammatory mediators being measured.

PMID- 9635461
TI  - Comparative evaluation of culture and PCR for the detection and determination of
      persistence of bacterial strains and DNAs in the Chinchilla laniger model of
      otitis media.
AB  - This study was designed to determine the persistence of culturable bacteria
      versus DNA in the presence of a middle ear effusion in a chinchilla model of
      otitis media. Cohorts of animals were either infected with an ampicillin
      resistant Haemophilus influenzae strain or injected with a tripartite inoculum
      consisting of freeze-thawed Streptococcus pneumoniae; pasteurized Moraxella
      catarrhalis; and DNA from H influenzae. The H influenzae-infected animals
      displayed culture positivity and polymerase chain reaction positivity through day
      35. In the chinchillas infected with the low-copy number inocula of S pneumoniae,
      DNA was not detectable after day 1 from the co-inoculated pasteurized M
      catarrhalis bacteria or the purified H influenzae DNA; however, amplifiable DNA
      from the live low-copy number bacteria persisted through day 21 even though they
      were not culture-positive past day 3. These results demonstrate that DNA, and DNA
      from intact but nonviable bacteria, does not persist in an amplifiable form for
      more than a day in the presence of an effusion; however, live bacteria, while not
      culturable, persist in a viable state for weeks.

PMID- 9635462
TI  - Sarcoidosis of the external nose mimicking rhinophyma. Case report and review of
      the literature.
AB  - A 52-year-old man with a large external nasal mass is presented. Initially, the
      mass was thought to be rhinophyma, but biopsy of the mass revealed noncaseating
      granulomata consistent with sarcoidosis. The mass resolved following several
      steroid injections. The case is discussed in detail, along with a review of the
      literature pertaining to sarcoidosis of the nose and nasal cavity.

PMID- 9635463
TI  - Branchial cleft cyst carcinoma: myth or reality?
AB  - Skepticism has surrounded the existence of branchial cleft carcinoma since the
      entity was first described in 1882. However, a landmark work of 1950 established
      four criteria for the diagnosis of branchial cleft carcinoma, the most important
      criterion being histologic proof of carcinoma arising from a normal cyst
      epithelium. Of the 43 cases found in an extensive review of the literature, only
      7 cases have satisfied all four of the criteria. To this we add 2 patients who
      had recurrent infections of a cervical cyst as children and later developed
      carcinoma within these structures. Additionally, we propose a minor modification
      to the 1950 criteria and a paradigm for diagnosis and management of these
      lesions.

PMID- 9635464
TI  - Age-related changes in the human laryngeal glands.
AB  - The present study was conducted to determine age-related changes in the human
      laryngeal glands by means of excised human adult larynges. Scanning and
      transmission electron microscopic observations were made. The results obtained
      are summarized as follows. 1) Granular endoplasmic reticulum and Golgi apparatus
      were sparse in the cytoplasm of serous and mucous cells. 2) Secretory granules in
      serous cells had decreased in number. 3) Secretory granules were less electron
      dense compared to those in younger adult specimens, but were electron-lucent. 4)
      Mucigen droplets in mucous cells were not as numerous as those in younger adults.
      5) Discharge of secretory granules and mucigen droplets had decreased. 6) Age
      related morphologic changes in the laryngeal glands influenced not only the
      amount but also the quality of secretions. 7) The above changes lessened
      lubrication of the vocal folds, thus causing aging of the voice to some extent.
      8) Local immunity and mucociliary transport were also affected. 9) Age-related
      changes in the laryngeal glands partially altered laryngeal function.

PMID- 9635465
TI  - Magnetic resonance sialography.

PMID- 9635466
TI  - Internal carotid artery aneurysm presenting as an unusual nasopharyngeal mass.

PMID- 9635467
TI  - Regional and distant metastases in laryngeal and hypopharyngeal sarcomas.
AB  - Cervical node and distant metastases are the most important prognostic factors in
      malignant laryngeal neoplasms. Owing to the unusual occurrence of laryngeal
      sarcomas, the prevalence of their metastases has never been analyzed in detail.
      We reviewed the laryngeal sarcomas reported in the literature and noticed that
      both regional and distant metastases are rare events and variable for different
      histotypes. These observations have obvious therapeutic and prognostic
      implications.

PMID- 9635468
TI  - Neurological and neuropsychological bases of empathy.
AB  - Impairments of social behavior after cerebral damage are often problematic and
      difficult to assess and manage, with few models addressing evaluation, treatment
      options and prognosis. Recent studies suggest that a fundamental mechanism of
      social behavior disturbed by acquired cerebral damage is empathy. Empathy refers
      to the cognitive and emotional processes that bind people together in various
      kinds of relationships that permit sharing of experiences as well as
      understanding of others. Empathic changes are particularly evident after focal
      prefrontal cortex damage and closed head injury in adults, though early frontal
      lobe damage is also associated with poor empathic and social development.
      Although alterations in empathy have been studied in only a handful of neurologic
      samples thus far, it may be an important outcome variable of brain injury,
      particularly in patients' adjustment to family, community and vocational
      settings. Treatment possibilities are presented, though more comprehensive
      research is needed.

PMID- 9635469
TI  - Central pathway of taste: clinical and MRI study.
AB  - We present 3 cases of hemiageusia due to focal ischemic lesions in the brainstem.
      Clinical presentation with discrete localization of these lesions suggests that
      the central taste pathway in humans projects ipsilaterally from the solitary
      nucleus up to the level of the upper pontine or lower midbrain before
      decussation. Associated partial sensory disturbance of the face or limb with lack
      of evidence of medial lemniscus decussation at the upper brainstem suggests that
      the medial lemniscus may not directly convey taste sensation.

PMID- 9635470
TI  - Isolated so-called apraxia of eyelid opening: report of 10 cases and a review of
      the literature.
AB  - So-called apraxia of eyelid opening (scAEO) has been described chiefly in the
      context of extrapyramidal disorders. We described 10 new patients with scAEO
      developing in the absence of any other CNS sign and reviewed the 11 cases with
      isolated scAEO reported in the literature. Combining our patients and those from
      the literature, peak age at onset was in the 6th decade and there was a female
      preponderance of 2:1. The characteristic inability to initiate lid elevation was
      frequently associated with failure to sustain lid elevation, thus suggesting that
      eyelid motor control may be abnormal in isolated scAEO. Antecedent events
      included ocular signs and symptoms consistent with diseases of eyes or face (4
      cases in our series and 2 in the literature), chronic treatment with flunarizine
      (1 case), and family history of dystonia (1 case). Flunarizine discontinuation
      led to sustained remission of the eyelid disturbance. Overall, these clues
      suggest the involvement of the extrapyramidal system in the pathophysiology of
      isolated scAEO. Familial clustering of isolated scAEO in one of our patients may
      be in favor of a genetic contribution. In our series, botulinum toxin
      administration close to the pretarsal part of the orbicularis oculi muscle
      significantly improved scAEO in 8/10 cases, whereas orbital/preseptal injection
      had no effect. We conclude that the term 'apraxia' may not be the correct
      descriptive term even when the eyelid disturbance occurs without any other CNS
      disease.

PMID- 9635471
TI  - Pure sensory syndromes in thalamic stroke.
AB  - We studied 25 patients with an acute thalamic stroke (infarct or hemorrhage) on
      CT or MRI scan and sensory dysfunction, among the 3,628 patients with first-time
      stroke included in the Lausanne Stroke Registry. Twelve patients had a right
      sided infarct, 11 a left-sided infarct, and 2 a left-sided thalamic hemorrhage.
      Sensory symptoms or signs were the only clinical abnormality. The presumed causes
      of stroke were small artery disease in 21 patients including both cases of
      hemorrhage, emboligenic heart disease in 2, while the etiology of ischemic stroke
      was undetermined in 2 patients. Nine patients had a loss of all modalities of
      sensation with faciobrachiocrural distribution, 5 patients suffered dissociated
      sensory loss with faciobrachiocrural distribution and 11 patients showed a
      dissociated involvement of sensation with a partial distribution pattern. The
      inferolateral region (thalamogeniculate arteries) was involved in all patients.
      Six patients complained of pain and/or dysesthesias during the stroke; 5 of them
      had involvement of the nucleus ventrocaudalis (in 3 with damage to the nucleus
      ventro-oralis intermedius, and in one to the pulvinar) and 1 patient had
      involvement of the nucleus ventro-oralis intermedius. Eighteen patients
      complained of paresthesias in the contralateral part of the body; 16 of them had
      involvement of the nucleus ventrocaudalis (in 4 with damage to the nucleus ventro
      oralis intermedius, in 1 with damage to the nucleus ventro-oralis intermedius,
      and nucleus ventro-oralis externus, and in one with damage to the nucleus
      parvocellularis and pulvinar). Four patients developed delayed pain and/or
      dysesthesias; all of them had involvement of the nucleus ventrocaudalis (in 1
      with damage to the nucleus parvocellularis and pulvinar). Time lag from stroke
      onset to developing pain ranged from 2 to 15 days (mean 10.5 days). One patient
      with dissociated involvement of sensation with a partial distribution pattern had
      paresthesias and dissociated hemisensory loss involving position sense without
      pain and temperature sensations. This patient had involvement of the
      posterolateral part of the nucleus ventrocaudalis. In conclusion, sensory
      dysfunction and delayed pain are more often found in thalamic lesions that
      involve the nucleus ventrocaudalis, and nucleus ventro-oralis intermedius.
      Restricted sensory abnormalities correlate with very small lesions located in
      critical areas within these nuclei.

PMID- 9635472
TI  - Muscle weakness in Parkinson's disease: isokinetic study of the lower limbs.
AB  - Isokinetic strength of knee extension and flexion was measured at two speeds of
      movement in 23 patients with Parkinson's disease, to clarify whether muscle
      weakness is inherent to the disease. To counteract normal variation among
      subjects, we selected patients with symptoms completely or largely confined to
      one side and compared sides for each patient. The affected side was weaker than
      the other in both slow and fast movements early in the disease. In more advanced
      disease, the difference between sides diminished at the slow speed but remained
      significant at the faster speed. These observations suggest that weakness is
      inherent to Parkinson's disease and influenced by movement speed.

PMID- 9635473
TI  - Thiopental in CSF and serum correlates with prolonged loss of cortical activity.
AB  - Barbiturate coma is initiated in brain-injured patients whenever elevated
      intracranial pressure remains unresponsive to other therapeutical strategies.
      However, barbiturates alter cortical activity resulting in difficulties in
      clinical evaluation. Therefore, we investigated the impact of long-term
      thiopental administration on responsiveness to exteroceptive stimuli in relation
      to pharmacokinetics of thiopental in CSF and serum. Long-term infusion increases
      thiopental levels which remain elevated for 6 and 9 days in CSF and serum,
      respectively, after termination of its administration. Prolonged unresponsiveness
      to exteroceptive stimuli correlates with persisting thiopental in CSF and serum.
      Thus, quantitative analysis of thiopental in serum becomes indispensable in
      predicting the length of drug-induced neurological impairment and in avoiding
      misinterpretation of the neurological status.

PMID- 9635474
TI  - Apolipoprotein E polymorphism in Alzheimer's disease: a comparative study of two
      research populations from Spain and the United States.
AB  - We examined the distribution of the apolipoprotein E (APOE) polymorphism in two
      Caucasian populations of Alzheimer's disease (AD) patients referred to dementia
      clinics; one in Gerona, Spain (66 AD patients, 49 controls), and the other in
      Pittsburgh, Pa., USA (209 AD patients, 58 controls). The presence of the APOE*4
      allele was a significant risk for developing AD in both cohorts: Gerona (odds
      ratio = 2.34, CI: 1.03-5.55) and Pittsburgh (odds ratio = 3.64, CI: 1.78-7.69).
      The proportion of AD with the APOE*4 allele was greater in the Pittsburgh cohort
      than in the Gerona cohort (p = 0.02). However, no statistical difference was
      noted between the two populations in nondemented controls (p = 0.41). These data
      emphasize the importance of geographical and ethnic variations in the study of
      APOE genotypes.

PMID- 9635475
TI  - Prevalence of dementia of Alzheimer type and apolipoprotein E phenotypes in aged
      patients with Down's syndrome.
AB  - We investigated the exact prevalence of dementia of Alzheimer type (DAT) and
      apolipoprotein E (ApoE) phenotypes in 106 Japanese Down's syndrome (DS) patients.
      Among these patients 16 were diagnosed as having DAT. The prevalence of DAT was
      0% in the 30- to 39-year-old group, 16% in the 40- to 49-year-old group, and 38%
      in those over 50 years old. The frequency of the epsilon4 allele in DS patients
      with DAT was 18.8%, which was considerably higher than that of nondemented DS
      patients (4.5%) and Japanese nondemented controls (6.7%). Especially, the
      frequency of the epsilon4 allele in DS patients who developed DAT under 50 years
      was significantly higher (28.6%). DS patients certainly develop DAT at earlier
      ages but the prevalence of DAT in each group of patients was lower than
      previously recognized. It is very likely that the ApoE epsilon4 is a risk factor
      for DAT even in DS patients with a genetic predisposition to Alzheimer's disease.

PMID- 9635476
TI  - Increased plasma concentration of atrial natriuretic hormone in myotonic
      dystrophy.
AB  - Atrial natriuretic hormone (ANH) concentrations were measured in 16 patients
      affected with myotonic dystrophy (MyD) undergoing 24-hour Holter ECG and in 15
      age-matched normal subjects. Although the MyD patients did not show overt left
      ventricular function impairment, their plasma ANH levels were found to be higher
      (183.76 +/- 113.25 pg/ml) compared to those of the control subjects (39.73 +/-
      9.95 pg/ml, p < 0.001). Nine patients with arrhythmias and some echocardiographic
      alterations formed subgroup A. Seven patients without cardiac alterations formed
      subgroup B. No significant difference in ANH emerged between the two subgroups.
      This evidence suggests that high plasma ANH levels in MyD cannot always be
      related to overt or latent heart failure and to arrhythmias.

PMID- 9635477
TI  - Reversible adverse effects on the CNS induced by histamine H2 receptor
      antagonists.

PMID- 9635478
TI  - Dysthyroid ophthalmopathy misinterpreted as ocular myositis.

PMID- 9635479
TI  - A retrospective study of infantile hydrocephalus observed in Benin.

PMID- 9635480
TI  - Cerebral venous thrombosis and estrogen-progesterone therapy.

PMID- 9635481
TI  - A case of carbamazepine-induced lymphadenopathy resembling Kikuchi disease.

PMID- 9635482
TI  - Successful treatment of focal epilepsy by fractionated stereotactic radiotherapy.

PMID- 9635483
TI  - A localized postoperative cervical syrinx revealed by orthostatic hypotension.

PMID- 9635484
TI  - Use of aquatic invertebrates in genotoxicological studies.

PMID- 9635485
TI  - Mutagen content and metabolic activation of promutagens by molluscs as biomarkers
      of marine pollution.
AB  - Organisms combat pollutants by inducing biotransformation pathways, which can be
      used for biomonitoring. Several parameters--biomarkers--change in stressed
      organisms or populations at different organisation levels. Molecular or cellular
      biomarkers are early-warning indicators of pollution. Xenobiotics are first
      biotransformed by phase I enzymes and then conjugated with endogenous metabolites
      by phase II enzymes. Many organic xenobiotics are initially biotransformed by
      cytochrome P4501A1; in mammals, it is induced by pollutants via Ah receptor,
      although in marine invertebrates, its inducibility is much more equivocal.
      Metallothioneins are small Cys-rich proteins which bind transition metals; they
      detoxicate pollutant metals and are clearly induced in metal-exposed marine
      invertebrates. Some pollutants are genotoxins or can be converted into them.
      Determination of mutagens in bivalve molluscs following extraction with solvents
      and assay of mutagenicity with bacterial tests is a useful biomarker for marine
      pollution. While some pollutants are directly mutagenic, others are only
      mutagenic after they are activated to mutagenic derivatives by monooxygenases or
      conjugative enzymes. Many of these catalysts are induced by xenobiotics; thus,
      increased activation of known promutagens can be used as biomarker of
      environmental pollution. Bioactivation of promutagens requires the simultaneous
      action of different pathways, thus, reproducing more closely the in vivo
      situation than the specific assay of individual biotransforming enzymes. Study of
      molluscs with different pollution levels indicates that polluted animals have
      higher capacity to activate 2-aminoanthracene and contain more apolar mutagens
      than those from reference areas.

PMID- 9635486
TI  - Tissue dose, DNA adducts, oxidative DNA damage and CYP1A-immunopositive proteins
      in mussels exposed to waterborne benzo[a]pyrene.
AB  - A collaborative study was performed on Mediterranean mussels (Mytilus
      galloprovincialis) exposed to a wide dose-range (0.5-1000 ppb) of benzo[a]pyrene
      (B[a]P). We selected this model polycyclic aromatic hydrocarbon in order to
      confirm the formation of a specific DNA adduct, previously detected in gill DNA,
      and to clarify the in vivo effects of this mutagenic chemical requiring host
      metabolism in mussels. B[a]P concentration reached consistently higher values in
      the digestive gland than in other analyzed tissues of mussels exposed to B[a]P
      for 2 or 3 days. With the exception of some values at 1000 ppb of B[a]P. DNA
      adduct levels increased significantly with the dose in gills and digestive gland
      and ranged from 0.054 to 0.789 adducts per 10(8) nucleotides (mean values per
      dose-point). Conversely, more complex dose-response relationships were found by
      detecting in parallel the levels of an oxidative DNA lesion (8-OHdG) and of CYP1A
      immunopositive proteins (the latter measured in the digestive gland only).
      Overall, the formation of DNA adducts, the evidence of oxidative DNA damage, and
      changes in CYP1A-immunopositive protein levels support the hypothesis that B[a]P
      can induce DNA damage in mussels through a number of different molecular
      mechanisms.

PMID- 9635487
TI  - The analysis of DNA adduct formation, removal and persistence in the common
      mussel Mytilus edulis exposed to 4-nitroquinoline 1-oxide.
AB  - 32P-postlabelling was used for the detailed analysis of 4-nitroquinoline 1-oxide
      (4-NQO) induced DNA adduct formation, removal and persistence in the marine
      shellfish Mytilus spp. The results had a number of important implications
      concerning the use of such DNA adducts as dosimeters of environmental genotoxin
      exposures. Our studies indicated that the maintenance of the Mytilus specimens
      under controlled laboratory conditions can result in the induction of 'stress
      related adducts' seemingly related to the nature of the experimental set-up. The
      studies also indicated that the absorption and activation of genotoxins in this
      species appear to affect the rate of adduct formation, and that the maximum
      levels of adducts may not necessarily be induced immediately after the cessation
      of a genotoxin exposure. In addition, Mytilus specimens were shown to possess a
      significant capacity to remove these genotoxin-induced DNA adducts. The removal
      of these adducts appeared to be biphasic in nature, with the rapid removal of a
      large proportion of adducts occurring within 48 h of the cessation of the
      exposure, followed by a slow rate of adduct removal over the remaining period of
      the studies. Despite the relatively efficient removal of the majority of these
      genotoxin-induced DNA adducts, a proportion remained up to 56 days after the
      initial exposure. The persistence of these genotoxin-DNA adducts, combined with
      the information on the rates of adduct removal, indicated that under well-defined
      conditions, such adducts could serve as suitable biomarkers of environmental
      contamination.

PMID- 9635488
TI  - The chemosensitizers of multixenobiotic resistance mechanism in aquatic
      invertebrates: a new class of pollutants.
AB  - Mechanism of multixenobiotic resistance (MXR), identical to multidrug resistance
      (MDR) in tumor cells, has been found in aquatic invertebrates. The presence of
      this ATP-dependent membrane P-glycoprotein (Pgp) pump was confirmed by
      biochemical ('binding'), molecular (immunohistochemical, Western, Northern),
      physiological (verapamil-sensitivity) and toxicological (modulation of toxicity)
      methods. The inducibility of MXR in the presence of xenobiotics and its wide
      taxonomic distribution suggests its role as a general biological defense
      mechanism that rescues organisms by pumping potentially toxic xenobiotics out of
      the cells. Some xenobiotics, the chemosensitizers, can inhibit this defense
      mechanism. The presence of these MXR-inhibitors has important implications on
      environmental parameters like exposure, uptake, internal dose, bioaccumulation,
      response, synergism and toxicity. Such MXR-inhibitors, for example, enhance the
      accumulation of carcinogenic aromatic amines in mussel, with subsequent
      enhancement in production of their mutagenic metabolites, in induction of single
      strand breaks in DNA, and in induction of DNA-adducts. The property to inhibit
      defense mechanism of organisms classifies MXR-inhibitors among top-hazardous
      environmental chemicals. Therefore, we measured the concentration of
      chemosensitizers in water concentrates or sediment extracts as their potential to
      modulate the accumulation of fluorescent dyes in a cell-culture of NIH 3T3 mouse
      fibroblasts stable transfected with human MDR1 gene, or as the potential of
      native waters to decrease the efflux-rate of Rhodamine B from gills of mussels.
      We found significantly higher concentrations of MXR-inhibitors in samples from
      polluted marine sites or from polluted rivers than in samples from corresponding
      unpolluted sites. These concentrations were able to enhance the accumulation of
      fluorescent dyes or carcinogenic aromatic amines in clams, mussels, snails and
      sponges exposed to these xenobiotics, demonstrating the ecotoxicological
      relevance of MXR-inhibitors present in polluted waters.

PMID- 9635489
TI  - Transgenic nematodes as biomonitors of microwave-induced stress.
AB  - Transgenic nematodes (Caenorhabditis elegans strain PC72), carrying a stress
      inducible reporter gene (Escherichia coli beta-galactosidase) under the control
      of a C. elegans hsp16 heat-shock promoter, have been used to monitor toxicant
      responses both in water and soil. Because these transgenic nematodes respond both
      to heat and toxic chemicals by synthesising an easily detectable reporter
      product, they afford a useful preliminary screen for stress responses (whether
      thermal or non-thermal) induced by microwave radiation or other electromagnetic
      fields. We have used a transverse electromagnetic (TEM) cell fed from one end by
      a source and terminated at the other end by a matched load. Most studies were
      conducted using a frequency of 750 MHz, at a nominal power setting of 27 dBm. The
      TEM cell was held in an incubator at 25 degrees C inside a shielded room;
      corresponding controls were shielded and placed in the same 25 degrees C
      incubator; additional baseline controls were held at 15 degrees C (worm growth
      temperature). Stress responses were measured in terms of beta-galactosidase
      (reporter) induction above control levels. The time-course of response to
      continuous microwave radiation showed significant differences from 25 degrees C
      controls both at 2 and 16 h, but not at 4 or 8 h. Using a 5 x 5 multiwell plate
      array exposed for 2 h, the 25 microwaved samples showed highly significant
      responses compared with a similar control array. The wells most strongly affected
      were those in the rows closest to the source, whereas the most distant row did
      not rise above control levels, suggesting a shadow effect. These differential
      responses are difficult to reconcile with general heating effects, although
      localised power absorption affords a possible explanation. Experiments in which
      the frequency and/or power settings were varied suggested a greater response at
      21 than at 27 dBm, both at 750 and 300 MHz, although extremely variable responses
      were observed at 24 dBm and 750 MHz. Thus, lower power levels tended, if
      anything, to induce larger responses (with the above-mentioned exception), which
      is opposite to the trend anticipated for any simple heating effect. These results
      are reproducible and data acquisition is both rapid and simple. The evidence
      accrued to date suggests that microwave radiation causes measurable stress to
      transgenic nematodes, presumably reflecting increased levels of protein damage
      within cells (the common signal thought to trigger hsp gene induction). The
      response levels observed are comparable to those observed with moderate
      concentrations (ppm) of metal ions such as Zn2+ and Cu2+. We conclude that this
      approach deserves further and more detailed investigation, but that it has
      already demonstrated clear biological effects of microwave radiation in terms of
      the activation of cellular stress responses (hsp gene induction).

PMID- 9635490
TI  - DNA damage in mussels at sites in San Diego Bay.
AB  - Identification and assessment of introduced and other toxicants is crucial to any
      comprehensive study of contaminants within the marine environment. The
      relationship between DNA single-strand breaks and the exposure of marine
      organisms to environmental contaminants was examined at sites in San Diego Bay,
      CA. A comprehensive assessment of the extent and consequences of marine
      environmental contamination in the area of Naval Station San Diego was conducted
      in the summer of 1995. The study addressed contamination sources, distributions,
      concentrations, transport, sediment-water exchange, biological effects, and
      degradation. The biological effects portion of the study (this paper) included
      contaminant bioaccumulation, organismal growth, and the determination of DNA
      single-strand breaks using the Comet assay. DNA damage was determined in
      hemocytes collected from deployed and resident mussels, Mytilus edulis, at six
      stations in and around the Naval Station San Diego. Deployed mussels were exposed
      on station for approximately 30 days in plastic mesh bags, placed 1 m above the
      bottom. Hemocyte samples were collected on days 0, 12, and 32. It was found that
      stations exhibiting the extremes of contaminant exposure, both highest and lowest
      concentrations, were easily identified using growth and DNA damage measurements.
      Sediment chemistry and bioaccumulation data indicated, Hg, Cu, and Zn, to be the
      most notable contaminants. The Comet assay, and in particular germ cell DNA
      damage determinations, were found to respond rapidly to station contaminants.
      Results from this study and an earlier 1993 study suggest that the non-sediment
      associated effects observed at one station may have been the result of the
      photoactivation of accumulated PAHs.

PMID- 9635491
TI  - Evaluation of the comet assay as a method for the detection of DNA damage in the
      cells of a marine invertebrate, Mytilus edulis L. (Mollusca: Pelecypoda).
AB  - The potential application of the comet assay for monitoring the effect of DNA
      damaging agents on the marine mussel, Mytilus edulis (an important pollution
      indicator organism), was explored. A detailed investigation of the baseline
      levels of single-strand breaks in isolated gill cells, and how they were affected
      by age/size of animal, time since collection, feeding regime, in vivo vs. in
      vitro exposure conditions, and by antioxidant supplementation was undertaken. The
      level of cometing in untreated controls was found to be highly variable over time
      (fluctuations between low and very high DNA damage occurred over just 14 days
      post collection). No difference was observed between age/size and feeding regime
      of the animals. On exposure to 0, 100, 500 and 1000 microM H2O2, it was observed
      that the in vitro exposure produced a markedly more homogeneous dose response
      compared to the in vivo studies (where gill cells were exposed as a tissue). An
      important finding of our research was the effect of prior supplementation of the
      animals' diet with 1 mg/ml alpha-tocopherol acetate (vitamin E compound), which
      resulted in a marked reduction in the levels of DNA damage expressed by the
      negative controls, without influencing the actual response to H2O2 (0, 5, 25, and
      100 microM) and N-nitrosodimethylamine, NDMA (0, 5, 25, and 100 mM). The effect
      of vitamin E supplementation was to increase the sensitivity of the comet assay
      at the lower end of the dose range. This study demonstrated the potential
      application of the comet assay to the gill cells of the mussel, M. edulis.
      Although preliminary findings suggest that antioxidant supplementation can
      improve the sensitivity of the assay by lowering the baseline damage in untreated
      animals, our conclusion is that the assay has more potential for use in an in
      vitro context for the screening of agents destined for release or disposal into
      the marine environment.

PMID- 9635492
TI  - Assessment of developmental effects, cytotoxicity and genotoxicity in the marine
      polychaete (Platynereis dumerilii) exposed to disinfected municipal sewage
      effluent.
AB  - While sodium hypochlorite is widely used as a disinfectant for municipal sewage
      effluents and power station cooling waters discharged into coastal environments,
      there is limited information on the potential in vivo genotoxicity of such
      disinfection procedures to marine organisms. Using a recently developed test
      system based on the marine polychaete Platynereis dumerilii, we have evaluated
      impacts based on embryo-larval development, cytotoxicity and genotoxicity
      following exposure to disinfected settled (primary) effluent from a municipal
      sewage treatment works (STW). Sewage samples were collected from Newton Abbot
      STW, Devon, UK and then disinfected with sodium hypochlorite based on standard
      operational procedures. Exposure of polychaetes to dilutions of disinfected
      sewage in seawater (20 +/- 1 degree C) led to a marked reduction in normal embryo
      larval development (7 h EC50 from 0.57-1.88% (v/v), n = 4), with a simultaneous
      increase in cytotoxicity. Following the calculation of the Maximum Tolerated Dose
      (MTD), based on developmental and cytotoxic effects, the organisms were also
      analysed for the induction of chromosomal aberrations. This investigation
      demonstrated the absence of genotoxicity in polychaetes exposed in vivo to sewage
      disinfected with sodium hypochlorite. These observations extend our previously
      published studies in which polychaetes exposed to non-disinfected sewage, while
      showing developmental toxicity and cytotoxicity, did not exhibit any evidence of
      cytogenetic damage.

PMID- 9635493
TI  - The ecotoxicological significance of genotoxicity in marine invertebrates.
AB  - Attention is drawn to the goals of genetic ecotoxicology, in particular, the need
      to relate genotoxicity in individuals to population and community level
      consequences. The evidence for pollutant-induced genotoxicity in marine
      invertebrates is reviewed. Neoplasia is apparently rare in marine invertebrates
      and only limited evidence is available to suggest that chemical genotoxins act as
      causative agents. It is unknown why marine invertebrates exhibit low tumour
      incidences and are much more tolerant of ionising radiation than their vertebrate
      counterparts. The importance of the genotoxic disease syndrome is highlighted.
      Disentangling phenotypic manifestations of genotoxic damage and that due to
      direct metabolic toxicity provides a major challenge for the future. Further work
      is required to assess the significance of interspecific and interindividual
      variability in susceptibility to genotoxicity, especially with regard to the
      evolution of resistant populations and communities of marine organisms at
      contaminated sites. Only by addressing the issues highlighted above can proper
      risk assessments of genotoxic agents be performed to minimise threats to human
      and ecosystem health.

PMID- 9635494
TI  - Characterization of fibronectin-related substances in normal and passive Heymann
      nephritis rats.
AB  - The excretion mechanism of fibronectin (FN)-related substances into the urine of
      normal and passive Heymann nephritis (PHN) rats was studied using enzyme
      immunoassay and immunoblot analysis. In normal rats, a small amount (0.20+/-0.067
      microg/d) of FN-related substances, composed of 55- and 65-kDa FN fragments
      derived from the central cell-binding (Cell) domain of FN, were constitutively
      excreted into the urine. When PHN was induced in rats by the injection of an anti
      Fx1A antibody, an increased excretion (4.96+/-3.51 microg/d) of intact FN and
      large (Mr > 100-kDa) FN fragments containing the Cell and the other functional
      domains were seen. The PHN induction also caused the appearance of a considerable
      amount of Cell domain-containing FN fragments in plasma. Both the renal cortex
      homogenates of normal and PHN rats were capable of degrading plasma FN to
      generate the Cell domain-containing large FN fragments. Degradation of FN by the
      renal cortex homogenate was shown to be due to metal and/or thiol proteinase(s).
      These results suggest that the PHN-induced urinary excretion of FN fragments may
      be due to the degradation of plasma FN by renal proteinases that may be leaked
      upon PHN induction.

PMID- 9635495
TI  - Low-dose irradiation induces expression of heat shock protein 70 mRNA and thermo-
      and radio-resistance in myeloid leukemia cell line.
AB  - We examined the effects of in vitro low-dose irradiation on myeloid leukemia
      cells (M1 cells) and found that it enhanced the colony-forming ability (CFA) of
      M1 cells in semi-solid agar. This enhancement was inhibited by treatment with a
      protein synthesis inhibitor, cycloheximide and with an RNA synthesis inhibitor,
      actinomycin D, after irradiation. These findings suggested that low-dose
      irradiation induced the synthesis of some proteins which were attributed to the
      enhancement of CFA. Since we expected that one species of these proteins were
      heat shock proteins (hsps), we attempted to detect the hsp70 family by the
      Western blotting method and inducible hsp70 mRNA by the RT-PCR method. Low-dose
      irradiation induced the expression of hsp70 mRNA, whereas the enhancement of
      hsp70 (an inducible isoform) and hsc70 (a constitutively expressed isoform)
      expression could not be found. Furthermore, the M1 cells showed thermoresistance
      1 h after low-dose pre-irradiation, and also showed radioresistance 4 h after
      irradiation. This time difference after pre-irradiation might be attributed to
      the different species of proteins in showing resistance to lethal stress.
      Therefore, some proteins other than hsp70 were believed to be concerned with the
      augmentation of CFA and the induction of thermo- and radio-resistance.

PMID- 9635496
TI  - Inhibitory effect of regucalcin on Ca2+/calmodulin-dependent phosphatase activity
      in rat renal cortex cytosol.
AB  - The effect of regucalcin, a Ca2+-binding protein, on Ca2+/calmodulin-dependent
      phosphatase activity in rat renal cortex cytosol was investigated. The addition
      of Ca2+/calmodulin in the enzyme reaction mixture caused a significant increase
      in the dephosphorylation of p-nitrophenylphosphate and phosphotyrosine used as
      the substrate for phosphatase in rat renal cortex cytosol. The presence of
      regucalcin (10(-6) M) in the enzyme reaction mixture caused a complete inhibition
      of Ca2+/calmodulin-dependent phosphatase activity in renal cortex cytosol. A half
      maximum effect of regucalcin inhibition was seen at 10(-8) M concentration.
      Moreover, phosphatase activity of purified calcineurin was significantly enhanced
      by the addition of Ca2+/calmodulin. This enhancement was completely inhibited by
      the presence of regucalcin (10(-7) M). The inhibitory effect of regucalcin was
      not weakened by increasing concentrations of CaCl2 (10(-6) to 10(-4) M). The
      present results suggest that regucalcin can inhibit Ca2+/calmodulin-dependent
      phosphatase activity in rat renal cortex.

PMID- 9635497
TI  - An ergosterol peroxide, a natural product that selectively enhances the
      inhibitory effect of linoleic acid on DNA polymerase beta.
AB  - As described previously (Mizushina Y., Tanaka N., Yagi H., Kurosawa T., Onoue M.,
      Seto H., Horie T., Aoyagi N., Yamaoka M., Matsukage A., Yoshida S., and Sakaguchi
      K., Biochim. Biophys. Acta, 1308, 256-262, 1996), linoleic acid (LA) inhibits the
      activities of mammalian DNA polymerases. We found a natural product from a
      basidiomycete, Ganoderma lucidum, that enhances this effect of LA in a special
      manner. The structure was identified to be an ergosterol peroxide, 5,8-epidioxy
      5alpha,8alpha-ergosta-6,22E-dien -3beta-ol by spectroscopic analyses. The
      ergosterol peroxide (EPO) itself scarcely inhibited the activities of calf thymus
      DNA polymerase alpha (pol. alpha) or rat DNA polymerase beta (pol. beta).
      However, when EPO at 0.25 mM was present, 10 microM or less of LA almost
      completely inhibited the pol. beta activity, while almost complete inhibition by
      LA itself was achieved at 80 microM or higher. Interestingly, under the same
      conditions, EPO did not affect the LA-effect on pol. alpha. The action mode of
      the EPO was discussed.

PMID- 9635498
TI  - Effects of YJA20379-4 on gastric secretion, Helicobacter pylori growth and
      various gastric and duodenal lesions in rats.
AB  - Effects of a newly synthesized antiulcer agent, YJA20379-4, on gastric proton
      pump (H+/K+-ATPase) activity, Helicobacter pylori (H. pylori) growth, gastric
      acid secretion, and gastro-duodenal lesions, were examined in comparison with
      those of omeprazole. YJA20379-4 markedly inhibited the H+/K+-ATPase activity in a
      concentration-dependent manner and the inhibitory effect was increased under a
      weak acidic condition; the IC50 values were 32 and 81 microM at pH 6.4 and 7.4,
      respectively. The inhibition was completely antagonized by 0.5 mM dithiothreitol
      (DTT). In addition, YJA20379-4 showed a significant anti-H. pylori activity
      determined by the agar dilution method. The value of minimum inhibitory
      concentration (MIC, 3.9-11.7 microg/ml) was at least 3 times more potent than
      that of omeprazole. In pylorus ligated rats, YJA20379-4 inhibited basal gastric
      acid secretion when administered by the intraduodenal route (ED50: 23.6 mg/kg).
      In experimental ulcer models, YJA20379-4 administered by the oral route dose
      dependently prevented the development of gastro-duodenal lesions in rats.
      Moreover, repeated administration of YJA20379-4 promoted the healing of gastric
      ulcers induced by acetic acid. On the basis of the data obtained, it is suggested
      that YJA20379-4 has a wide spectrum of antiulcer activities, and its mode of
      antiulcer actions is dependent on the inhibition of H+/K+-ATPase activity and H.
      pylori growth and the enhancement of a mucosal defense. Thus, YJA20379-4 might
      prove to be a beneficial therapy for gastritis and peptic ulcer diseases.

PMID- 9635499
TI  - Histamine-releasing properties of T-3762, a novel fluoroquinolone antimicrobial
      agent in intravenous use. I. Effects of doses and infusion rate on blood
      pressure, heart rate and plasma histamine concentration.
AB  - T-3762, a newly developed fluoroquinolone antimicrobial agent, ciprofloxacin
      (CPFX) and ofloxacin (OFLX) were administered intravenously to anesthetized dogs
      by intravenous infusion, and blood pressure, heart rate and plasma histamine
      concentrations were monitored. T-3762 decreased blood pressure by 12.0%, without
      alterations in heart rate and plasma histamine concentration, only when infused
      at 150 mg/min. CPFX and OFLX both produced a rapid decrease in blood pressure in
      a dose-related manner, with an accompanying decrease in heart rate, but to a
      lesser extent. After infusion at 150 mg/min, CPFX caused death in 2 animals
      within a few minutes, while OFLX produced maximum decreases in blood pressure and
      heart rate, by 69.0% and 26.4%, respectively. The infusion of these 2 agents
      resulted in dose-related increases in plasma histamine concentrations parallel to
      the decreases in blood pressure: the maximum, attained with CPFX at 50 mg/min and
      OFLX at 150 mg/min, were 379.2 and 167.8 ng/ml, respectively. For CPFX and OFLX,
      the relationship between the maximum levels of decreased blood pressure and
      increased histamine concentration in plasma was highly significant. The
      hypotension induced by CPFX was efficiently reduced by the pretreatment of
      animals with antihistamines. The results from this study suggest that hypotension
      induced in dogs following the intravenous infusion of fluoroquinolone
      antimicrobial agents may be dependent on their ability to cause histamine release
      from cells and tissues, and indicates that T-3762 is devoid of this ability in
      comparison to CPFX and OFLX.

PMID- 9635500
TI  - Histamine-releasing properties of T-3762, a novel fluoroquinolone antimicrobial
      agent in intravenous use. II. Dermovascular permeability-increasing effect and
      action on peritoneal mast cells.
AB  - To predict the actions of T-3762, a newly developed fluoroquinolone antimicrobial
      agent, as well as ciprofloxacin (CPFX) and ofloxacin (OFLX), on injection sites
      when dosed parenterally, their ability to increase cutaneous vascular
      permeability in dogs and to release histamine from rat peritoneal mast cells was
      examined. CPFX and OFLX increased cutaneous vascular permeability in
      concentrations ranging from 16 to 32 microg/ml, while T-3762 was inactive at 2000
      microg/ml. The vascular permeability-increasing activities of these drugs were
      inhibited efficiently by pretreatment with a combined dose of diphenhydramine and
      cimetidine. CPFX induced histamine release from rat mast cells in a dose
      dependent manner, whereas T-3762 was ineffective. Therefore, it is concluded that
      fluoroquinolone antimicrobial agents may have the ability to cause an increase in
      cutaneous vascular permeability by releasing histamine from mast cells at the
      injection site when administered parenterally, and that T-3762 has minimum
      activity among the agents tested in this study.

PMID- 9635501
TI  - Twist form of teleocidin derivatives is active in in vivo tumor promotion by (-)
      benzolactam-V8-310.
AB  - Teleocidin derivatives and the core structure, (-)-indolactam-V ((-)-IL-V), adopt
      two conformations in solution, the "twist" and the "sofa" forms. (-)-Benzolactam
      V8-310 ((-)-BL-V8-310), which specifically adopts the twist form in solution, has
      been reported to have a significant effect on HL-60 cells and protein kinase C
      affinity. In this paper, we describe the biological activity with regard to tumor
      promotion on mouse skin and the wide variety of biological activity of (-)-BL-V8
      310 and its derivatives. In both twist and sofa forms (-)-BL-V8-310 inhibited
      specific 3H-12-O-tetradecanoylphorbol-13-acetate (TPA) binding to a particulate
      fraction of mouse skin more strongly than (-)-IL-V. The doses for 50% inhibition
      (IC50) of (-)-IL-V, (-)-BL-V8-310, and teleocidin B-4 were 1000, 400 and 12 nM,
      respectively. As for the induction of tumor necrosis factor-alpha (TNF-alpha)
      release into the medium from HL-60 cells, the EC200 values, which are the
      concentrations of the compound required to achieve 200 pg/ml TNF-alpha in the
      medium, were 1700, 500 and 19 nM for (-)-IL-V, (-)-BL-V8-310 and teleocidin B-4,
      respectively. The same amounts (5.5 nmol per application) of (-)-BL-V8-310 and
      teleocidin B-4, induced tumors on mouse skin initiated with 7,12
      dimethylbenz(a)anthracene (DMBA) in 13.3% and 86.7% of tumor-bearing mice,
      respectively, in week 20. These results confirmed that the twist form of
      teleocidin derivatives is the active form as far as the induction of biological
      activity is concerned. Also (-)-BL-V8-310 is a new synthetic tumor promoter
      designed from data obtained using the receptor cavity model of TPA-type tumor
      promoters.

PMID- 9635502
TI  - Antihypertensive effect of sesamin. III. Protection against development and
      maintenance of hypertension in stroke-prone spontaneously hypertensive rats.
AB  - The antihypertensive effect of sesamin, a lignan from sesame oil, was examined
      using salt-loaded and unloaded stroke-prone spontaneously hypertensive rats
      (SHRSP). The animals at 6 weeks of age were separated into a salt-loaded group
      and an unloaded group. Salt-loaded animals were maintained on 1% NaCl drinking
      water. Each group was further divided into two groups: normal-diet group and
      sesamin-diet group. Systolic blood pressure of all animals was monitored once
      weekly. At the end of the feeding periods, cardiovascular hypertrophy and renal
      damage were evaluated. In the salt-loaded group, sesamin feeding significantly
      suppressed the development of hypertension, and efficient suppression was
      maintained from 9 to 26 weeks (e.g., 215+/-4 vs. 180+/-4 mmHg, at 17 weeks old).
      The left ventricle plus septum weight-to-body weight ratio was slightly but
      significantly lowered by sesamin feeding. When the degree of vascular hypertrophy
      of the aorta and superior mesenteric artery was histochemically evaluated, wall
      thickness and wall area of these vessels were significantly decreased by the
      sesamin feeding. Histological renal damage such as thickening of the tunica
      intima and fibrinoid degeneration of the arterial wall were often observed in the
      normal-diet group, but this damage was efficiently reduced in the sesamin-fed
      animals. On the other hand, in the salt-unloaded group, only a slight and
      nonsignificant suppressive effect of sesamin on the development of hypertension
      was observed. Although the wall area of the aorta was significantly decreased by
      the sesamin feeding, other vascular parameters were not ameliorated. The
      incidence of histological renal damage tended to decrease in sesamin-fed animals,
      but these alterations were not statistically significant. Thus, sesamin feeding
      was much more effective as an antihypertensive regimen in salt-loaded SHRSP than
      in unloaded SHRSP, thereby suggesting that sesamin is more useful as a
      prophylactic treatment in the malignant status of hypertension and/or
      hypertension followed by water and salt retention.

PMID- 9635503
TI  - Phylogenetic analysis of Atractylodes plants based on chloroplast trnK sequence.
AB  - The phylogenetic relationship of Atractylodes lancea, A. chinensis, A. koreana,
      A. ovata and A. japonica were analyzed by comparing the 2.6 kb sequence in a
      chloroplast gene trnK encoding tRNALys (UUU). The dried rhizomes of the former
      three species have been used as the crude drug "So-jutsu" and those of the latter
      two as "Byaku-jutsu" in Chinese and Japanese traditional medicine ("Kampo
      medicine"). The trnK phylogenetic tree revealed that A. ovata is an outgroup of
      the five Atractylodes species examined and that A. japonica and A. lancea are
      most closely related. PCR amplification of trnK with HinfI digestion provided us
      with a simple method to distinguish A. ovata from other Atractylodes species at
      the molecular level.

PMID- 9635504
TI  - Atractylodes lancea autotetraploids induced by colchicine treatment of shoot
      cultures.
AB  - Two strains of autotetraploid plants of Atractylodes lancea DC. (Compositae) were
      raised from the in vitro colchicine-treated shoot cultures, and field trials were
      performed to evaluate their growth and the amount of essential oil components in
      the rhizome in comparison with the corresponding diploids. The tetraploid plants
      had larger leaves than the diploids. One of the selected tetraploid lines had
      about 1.5 times as heavy rhizomes as the diploid and contained atractylodin,
      hinesol and beta-eudesmol in the rhizome to as great an extent or slightly less
      than the diploids. However, the contents of these constituents in the rhizome of
      the other tetraploid strain were lower than the diploids. The chloroplast number
      per guard cell, stomatal length, and stomatal density of leaf lower epidermis of
      the shoot cultures were good indicators for distinguishing tetraploids from
      diploids.

PMID- 9635505
TI  - Skin penetration enhancing action of cis-unsaturated fatty acids with omega-9,
      and omega-12-chain lengths.
AB  - The skin penetrative action of high purity cis-omega-12-octadecenoic acid
      (petroselinic acid, HP-PSA) on rat skin was compared with that of high purity cis
      omega-9-octadecenoic acid (oleic acid, HP-OA), following treatment of rat intact
      skin surface with either 0.05 M HP-PSA or HP-OA in propylene glycol (PG), using
      Fourier transform/attenuated total reflection (FT-IR/ATR) analysis. Both HP-PSA
      and HP-OA disordered the lipid structures of the stratum corneum region to a
      similar extent. Removal of the extractable lipids of the stratum corneum region
      was marked with HP-PSA/PG but was very slight upon HP-OA/PG treatment. The
      spectra of the amide II region which originated from proteins suggests that HP
      PSA/PG more rapidly disordered the protein structures of both the stratum corneum
      and the dermis than HP-OA/PG. However, the extent of disordering of the protein
      structures was presumed to be similar between these two skin penetration
      enhancers at the maximum level. Enhancement of PG flux in the dermis showed
      strong positive correlation with the degree of dermis-disordering action of HP
      PSA/PG and HP-OA/PG. These results demonstrate that HP-PSA, which has a double
      bond at an even numbered position (omega-12), more rapidly affects the
      perturbation of the structures of both the stratum corneum and the dermis than HP
      OA, which has the double bond at an odd numbered position (omega-9). Differences
      in the physicochemical properties of HP-PSA and HP-OA which originate from
      differences in the double bond position most likely determine the efficacy of
      these compounds as skin penetration enhancers.

PMID- 9635506
TI  - Control of plasma cholesterol-lowering action of probucol with various lipid
      carrier systems.
AB  - In order to explore the relationship between the pharmacokinetic properties and
      pharmacological actions of lipophilic drugs injected with lipid carrier systems,
      probucol was selected as a model drug with high lipophilicity, and the effect of
      disposition control on cholesterol-lowering activities was evaluated. Both large
      emulsion, with mean diameter of 280 nm, and long-circulating type small emulsion
      containing egg sphingomyelin with mean diameter of 100 nm, showed stable
      incorporation of probucol. The former produced rapid accumulation of probucol in
      the liver, while the latter demonstrated prolonged systemic circulation and
      gradual hepatic uptake. On the other hand, injection of a micellar solution with
      HCO-60 (polyoxyethylene hydrogenated castor oil) showed a rapid decrease in
      plasma concentration and a high hepatic uptake of probucol, similar to injections
      with serum, suggesting the rapid release of the drug from the micelles. However,
      probucol in a micellar solution showed higher cholesterol-lowering action than
      that in emulsion formulations. These results suggested that the pharmacological
      action of probucol in the liver might be affected by the uptake mode and
      sequential disposition in the organ, depending on the drug retention properties
      of the lipid carrier particles.

PMID- 9635507
TI  - Studies on the antiviral mechanisms of protein kinase inhibitors K-252a and
      KT5926 against the replication of vesicular stomatitis virus.
AB  - We investigated the antiviral mechanisms of K-252a, a broad non-specific protein
      kinase inhibitor which was isolated from Nocardiopsis sp. and its derivative
      (KT5926), against vesicular stomatitis virus (VSV) replication in BHK-21 cells.
      Although K-252a (5 microM) and KT5926 (15 microM) similarly suppressed the viral
      primary and secondary transcriptions and genomic RNA synthesis in vivo, the
      inhibitory mechanisms did not seem to be the same; phosphorylation of the viral
      NS protein was suppressed by K-252a, which might account for the decreased viral
      RNA synthesis caused by K-252a. On the other hand, KT5926, being known to
      preferentially inhibit myosin light chain kinase (MLCK), had little effect on NS
      protein phosphorylation. Cellular casein kinase II, which is believed to be
      involved in the phosphorylation of the N-terminal side (domain I) of NS protein,
      was not inhibited at all by KT5926 even at 15 microM under in vitro assay
      conditions, and was only weakly inhibited by K-252a at 1 to 10 microM. Neither
      inhibitor seemed to directly affect viral protein synthesis, but affected it
      indirectly as a secondary effect of reduced viral RNA synthesis. These results
      suggest that both the KT5926-sensitive and the KT5926-resistant but K-252a
      sensitive functions are involved in the essential processes of viral RNA
      synthesis. The KT5926-sensitive function(s) might not be involved in the NS
      protein phosphorylation, but may participate in some other way in the process of
      virus replication. On the other hand, the KT5926-resistant, K-252a-sensitive
      function(s) are probably involved in NS protein phosphorylation. The possible
      nature of those functions is discussed.

PMID- 9635508
TI  - Immunocytochemical localization of salivary peptide P-C in human submandibular
      gland.
AB  - Human saliva contains a proline-rich polypeptide, salivary peptide P-C, which
      potentiates insulin release and reduces glucagon release from perfused rat
      pancreas to decrease blood glucose level. To elucidate the process of secretion
      into humoral fluid of this peptide morphologically, we investigated
      ultrastructural localization of P-C in human submandibular gland by immunogold
      technique with anti-peptide P-C whose specificity to P-C was confirmed by
      immunoblotting. The labeling with gold particles which represents the
      distribution of P-C-like-immunoreactivity (P-C-LI) was detected in the secretory
      granules and rough endoplasmic reticula of the acinar serous cells and in few
      mucosa cells. P-C-LI was also observed in the lumen of striated duct but not
      intracellularly in the ductal cells themselves, indicating that P-C is not
      probably reabsorbed there. These results suggest that salivary peptide P-C is
      present in acinar serous cells, is secreted into the oral cavity, and may be
      reabsorbed through the digestive tract to modulate the blood glucose level after
      feeding.

PMID- 9635509
TI  - Synthesis of a biologically active fluorescent derivative of GM1, a main Ginseng
      saponin metabolite formed by intestinal bacteria.
AB  - A fluorescent derivative of GM1 [20-O-beta-D-glucopyranosyl-20(S)
      protopanaxadiol], a main Ginseng saponin metabolite formed by intestinal
      bacteria, was obtained from the condensation of its trisnor-aldehyde derivative
      with dansyl hydrazine. The dansylated GM1 fluoresced strongly and showed almost
      the same properties as its parent compound in lipophilicity and biological
      activities, so this fluorescent compound might provide an insight into the
      mechanism of pharmacological activities of GM1.

PMID- 9635510
TI  - Enhancement of the vanadate-stimulated release of lipoprotein lipase activity by
      astilbin from the leaves of Engelhardtia chrysolepis.
AB  - Astilbin, a dihydroflavonol rhamnoside isolated from the leaves of Engelhardtia
      chrysolepis, enhanced the vanadate-stimulated release of lipoprotein lipase (LPL)
      activity from rat isolated fat pads. N-[2-(Methyl-amino)ethyl]-5
      isoquinolinesulfonamide (H-8), a potent inhibitor of cAMP-dependent protein
      kinase (PKA), markedly inhibited the enhancement by astilbin. Lipolysis in the
      fat pads was stimulated by astilbin alone in a dose-dependent manner and this
      stimulation was suppressed in the presence of vanadate, probably due to its
      antilipolytic action. A significant enhancement by astilbin was observed with
      increasing effects of vanadate on cAMP content in the fat pads and on cAMP
      phosphodiesterase (PDE) activity in the particulate fraction although astilbin
      alone showed only a slight increase in the cellular cAMP content and PDE
      activity. Astilbin may enhance the vanadate-stimulated release of LPL activity
      through a synergistic effect on an increase in the cellular cAMP content produced
      by vanadate accompanied by more potent activation of PKA.

PMID- 9635511
TI  - Protective effect of ceftriaxone against the nephrotoxicity of isepamicin
      administered once daily in rats.
AB  - The protective effect of ceftriaxone on isepamicin-induced nephrotoxicity was
      investigated. For 14 d, Wistar rats were administered either ceftriaxone 100
      mg/kg intraperitoneally, isepamicin 300 mg/kg subcutaneously, or ceftriaxone
      isepamicin in combination. The animals given 300 mg/kg of isepamicin showed a
      significant increase in urine NAG (N-acetyl-beta-D-glucosaminidase) levels as
      compared with the control animals which received saline (p<0.01). However, the
      increase in NAG level was markedly less when isepamicin was administered in
      combination with ceftriaxone (p<0.01). Ceftriaxone alone had no effect on urine
      NAG activity. Serum creatinine levels were significantly higher in animals
      treated with isepamicin alone than in control animals (p<0.01) or animals
      receiving the isepamicin ceftriaxone combination (p<0.01). After 14 d of
      treatment, ceftriaxone had not accumulated in renal tissue, but it did reduce the
      renal intracortical accumulation of isepamicin (p<0.01). Histopathologically,
      ceftriaxone induced very few cellular alterations and considerably reduced the
      manifestation of typical signs of isepamicin nephrotoxicity. This investigation
      demonstrates that ceftriaxone protects animals against isepamicin-induced
      nephrotoxicity.

PMID- 9635512
TI  - Effect of potassium sorbate on cellular GSH level and lipid peroxidation in
      cultured rat hepatocytes.
AB  - Change in cellular reduced glutathione (GSH) level was examined after the
      addition of 1-10 mM potassium sorbate (SA-K) to cultured rat hepatocytes. The
      cellular GSH content was decreased to the lowest level at 6 h after the addition
      of SA-K, and then gradually returned to the normal level except for hepatocytes
      exposed to 10 mM SA-K. Although the decrease in GSH level was not associated with
      lactate dehydrogenase (LDH) leakage in hepatocytes exposed to SA-K up to the
      concentration of 5 mM, cell injury was caused in cells exposed to 10 mM SA-K.
      When eicosapentaenoic acid was added in conjunction with various concentrations
      of SA-K to hepatocytes, peroxidation of the fatty acid was accelerated in
      parallel with the decrease in cellular GSH level. The enhanced lipid peroxidation
      in the hepatocytes co-exposed to SA-K and eicosapentaenoic acid (EPA) induced the
      development of cell injury. These results suggest that hepatocytes exposed to SA
      K become susceptible to oxidative stress such as lipid peroxidation.

PMID- 9635513
TI  - Uptake of doxorubicin by cultured kidney epithelial cells LLC-PK1.
AB  - The renal handling of doxorubicin (DXR) was investigated using a kidney
      epithelial cell line, LLC-PK1. The uptake of DXR by LLC-PK1 cells cultured on
      plastic dishes was shown to be temperature and concentration dependent. The
      initial uptake of DXR was slightly saturable. The Km and Vmax of the saturable
      component were calculated to be 20.2 microM, and 0.355 nmol/mg protein/10 min,
      respectively. The release of DXR from LLC-PK1 cells was very slow at 37 degrees C
      and almost negligible at 4 degrees C, indicating that most of the DXR in the
      cells irreversibly binds to cellular constituents and that only a slight amount
      of unbound DXR participates in the efflux out of the cells. DXR uptake at 37
      degrees C was significantly decreased in the presence of 2,4-dinitrophenol.
      However, organic cations and aminoglycoside antibiotics, such as
      tetraethylammonium, N1-methylnicotinamide, guanidine, gentamicin and neomycin,
      did not inhibit DXR uptake, suggesting that a process distinct from the organic
      cation transport system and absorptive endocytosis might be involved in the
      uptake of DXR by LLC-PK1 cells.

PMID- 9635514
TI  - Isolation of a major metabolite (i-OHAP) of aprindine and its identification as N
      [3-(N,N-diethylamino)propyl]-N-phenyl-2-aminoindan-5-ol.
AB  - i-OHAP, a major metabolite of aprindine (AP), was isolated by TLC from rat feces
      and identified as N-13-(N,N-diethylamino)propyl]-N-phenyl-2-aminoindan-5-ol,
      based on 1H-NMR, the H-H correlation spectroscopy (COSY) spectrum, MS and LC-MS.
      Its structure was also confirmed by comparison with the synthesized compound. The
      hydroxy group of i-OHAP was located at the 5-position of the indan ring. AP is a
      prochiral compound, and the metabolism of AP to i-OHAP was stereoselective. The
      ratio of (+)/(-)-i-OHAP in rat feces and in human urine was about 5 and 15,
      respectively.

PMID- 9635515
TI  - A rapid assay of granisetron in biological fluids from cancer patients.
AB  - A convenient high-performance liquid chromatography (HPLC) was developed for the
      rapid assay of granisetron (GRN) in biological fluids, such as serum, urine, and
      pleural effusion, from cancer patients. Extrelut-1 was used for the solid-phase
      extraction. HPLC was carried out using a LiChroCART cartridge column packed with
      Lichrospher 100 CN and a mobile phase consisting of 0.1 M acetate buffer (pH 3.5)
      and acetonitrile (7:3). A fluorescence detector of 290 nm for excitation and 365
      nm for emission was used. The standard curve was linear over the range of 2 to
      100 ng/ml of GRN. Assay precision, expressed as a coefficient of variation
      (C.V.), was in the range of 0.9-5.4% in the within-day assay and 2.5-6.9% in the
      between-day assay, respectively. GRN was well separated on the HPLC chromatogram
      from drugs such as etoposide, metclopramide, ondansetron, and domperidone which
      are often used together with GRN. It was suggested that the present method is
      useful for the rapid monitoring of GRN in the serum, urine, and pleural effusion
      of patients undergoing cancer chemotherapy.

PMID- 9635516
TI  - Inhibitory effect of 2,5-dimethylpyrazine on oxytocic agent-induced uterine
      hypercontraction of normal or pregnant female rats.
AB  - Intraperitoneal administration of 2,5-dimethylpyrazine (2,5-DMP) was found to
      inhibit oxytocin- and prostaglandin F2alpha-induced tetanic uterine contractions
      in normal or pregnant female rats. This suggests that 2,5-DMP may be used as a
      countercontraction agent or relaxant for preventing oxytocic agent-induced
      medical accident including uterine rupture or pressure death of the fetus due to
      uterine contractions.

PMID- 9635517
TI  - Inhibition of S-warfarin metabolism by nonsteroidal antiinflammatory drugs in
      human liver microsomes in vitro.
AB  - We studied the inhibition of S-warfarin metabolism by nonsteroidal
      antiinflammatory drugs (NSAIDs) in human liver microsomes in vitro. After
      screening for potential inhibitors among ten NSAIDs using human recombinant
      cytochrome P450, inhibition kinetic parameters were estimated using human liver
      microsomes. Phenylbutazone and bucolome were suggested to increase the unbound
      steady-state level of S-warfarin about four- and five-fold, respectively, as
      estimated from these metabolic parameters.

PMID- 9635518
TI  - Potent retinoid synergists with a diphenylamine skeleton.
AB  - 4-[N-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)amino]benzoic acid (5)
      exhibited weak retinoidal and retinoid synergistic activities in HL-60 cell
      differentiation assay. N-Alkylation of 5 caused decrease or loss of
      differentiation-inducing activity, but enhanced the synergistic activity with a
      synthetic retinoid Am80 (2), as reflected in the potent synergistic EC50 (SEC50)
      values of DA023 (11, 1.6 x 10(-10) M) and DA113 (14, 1.4 x 10(-10) M) in the
      presence of 1.0 x 10(-10) M Am80 (2).

PMID- 9635519
TI  - Novel thiazolidinedione derivatives with retinoid synergistic activity.
AB  - Several arylmethylidene thiazolidinediones were synthesized and their retinoidal
      activities were examined. TZ181 (7a), having a benzanilide skeleton, exhibited
      differentiation-inducing activity in HL-60 cell assay, while TZ191 (7b), the N
      methylated analog of TZ181 (7a), TZ245 (9) and TZ335 (10) acted as retinoid
      synergists like the RXR-selective ligand, LGD1069 (5).

PMID- 9635520
TI  - Controlled-release morphine tablets in patients with chronic cancer pain: a
      narrative review of controlled clinical trials.
AB  - BACKGROUND: Controlled-release (CR) morphine tablets have become routine therapy
      in the management of cancer pain. Compared with immediate-release (IR) morphine,
      this formulation provides the benefit of dosing every 12 hours. METHODS: This
      study reviewed the 10 published, well controlled, repeated-dose, comparative
      studies with CR morphine tablets administered every 12 hours to patients with
      cancer pain. RESULTS: CR morphine tablets were uniformly effective; 98% of
      patients completed a treatment course of every-12-hours therapy. Although the
      effective analgesic dose varied considerably from study to study (range, 90-330
      mg per day), pain was well controlled with CR morphine tablets as the primary
      analgesic. Mean pain scores, converted to a common 10-point scale, ranged from
      1.1-2.9 across all studies. There was only occasional need for IR morphine rescue
      medication (range, 2-39 mg per day). The mean discontinuation rate because of
      side effects or lack of every-12-hours efficacy was 2%. In seven studies that
      used IR morphine as the comparative agent, CR morphine tablets were found to be
      equally effective as IR morphine. CONCLUSIONS: Twice-daily dosing of CR morphine
      provides convenient, safe, and effective relief of cancer pain.

PMID- 9635521
TI  - Long-term survival of patients with stage IV gastric carcinoma.
AB  - BACKGROUND: Survival of patients with Stage IV (based on general rules
      established by the Japanese Research Society for Gastric Cancer) gastric
      carcinoma often is unfavorable. Among patients with a poor prognosis, a few do
      survive > 5 years. The authors examined pathologic and biologic features of
      tumors of long term survivors. METHODS: The authors analyzed data from 442
      patients with Stage IV gastric carcinoma, including 20 surviving for > 5 years
      after gastrectomy (Group A) and 422 who died of gastric carcinoma within 5 years
      (Group B). Mutant p53 was immunohistochemically stained using the monoclonal
      antibody PAb1801. Proliferative activity was estimated by argyrophilic nuclear
      organizer region (AgNOR) staining and proliferating cell nuclear antigen (PCNA)
      staining. RESULTS: Group A had smaller and more localized tumors than Group B (P
      < 0.05 and P < 0.01, respectively). Lymphatic or venous invasion and peritoneal
      dissemination were less frequent in Group A than in Group B (P < 0.01).
      Abnormalities of p53 expression were found in 3 of the 14 tumors in Group A
      (21%), a value significantly lower than the 58 of 118 tumors in Group B (49%; P <
      0.05). AgNOR count and percentage of PCNA labeling were not significantly
      different between Groups A and B. A multivariate analysis showed that lymph node
      dissection, liver metastasis, gastric resection, venous invasion, and tumor size
      were independent prognostic factors. CONCLUSIONS: Even in patients with Stage IV
      gastric carcinoma, radical gastrectomy and extensive lymph node dissection can
      lead to long term survival. The authors believe that combination analysis of
      pathologic features and p53 overexpression predict length of survival for
      patients with Stage IV gastric carcinoma.

PMID- 9635522
TI  - Race, treatment, and survival among colorectal carcinoma patients in an equal
      access medical system.
AB  - BACKGROUND: The aim of this study was to assess the influence of race on the
      treatment and survival of patients with colorectal carcinoma. METHODS: This
      retrospective cohort study included all white or black male veterans given a new
      diagnosis of colorectal carcinoma in 1989 at Veterans Affairs Medical Centers
      nationwide. After adjusting for patient demographics, comorbidity, distant
      metastases, and tumor location, the authors determined the likelihood of surgical
      resection, chemotherapy, radiation therapy, and death in each case. RESULTS: Of
      the 3176 veterans identified, 569 (17.9%) were black. Bivariate analyses and
      logistic regression revealed no significant differences in the proportions of
      patients undergoing surgical resection (70% vs. 73%, odds ratio 0.92, 95%
      confidence interval 0.74-1.15), chemotherapy (23% vs. 23%, odds ratio 0.99, 95%
      confidence interval 0.78-1.24), or radiation therapy (17% vs. 16%, odds ratio
      1.10, 95% confidence interval 0.85-1.43) for black versus white patients. Five
      year relative survival rates were similar for black and white patients (42% vs.
      39%, respectively; P=0.16), though the adjusted mortality risk ratio was modestly
      increased (risk ratio 1.13, 95% confidence interval 1.01-1.28). CONCLUSIONS:
      Overall, race was not associated with the use of surgery, chemotherapy, or
      radiation therapy in the treatment of colorectal carcinoma among veterans seeking
      health care at Veterans Affairs Medical Centers. Although mortality from all
      causes was higher among black veterans with colorectal carcinoma, this finding
      may be attributed to underlying racial differences associated with survival. This
      study suggests that when there is equal access to care, there are no differences
      with regard to race.

PMID- 9635523
TI  - A phase II trial of 5-fluorouracil, leucovorin, and carboplatin in patients with
      unresectable biliary tree carcinoma.
AB  - BACKGROUND: Unresectable adenocarcinoma of the biliary tree are associated with a
      very poor prognosis. 5-fluorouracil (5-FU) combination regimens have produced
      objective response rates in approximately 10-20% of patients. Leucovorin
      increases the selective cytotoxicity of 5-FU. There also are encouraging reports
      of carboplatin in combination with 5-FU in other gastrointestinal tract
      malignancies. METHODS: Fourteen consecutive eligible patients were treated with a
      combination of carboplatin, 300 mg/m2, intravenously (i.v.) on Day 1 only and 5
      FU, 400 mg/m2, i.v. with leucovorin, 25 mg/m2, i.v. on Days 1-4. All patients
      were required to have a histologically confirmed diagnosis and measurable
      disease. Patients were evaluated for response, survival, and toxicity. RESULTS: A
      total of 48 cycles of therapy were delivered. The median survival was 5 months.
      One patient achieved complete remission and two others partial remission, for a
      total response rate of 21.4%. Four additional patients had stable disease for a
      median duration of 4 months. The therapy was well tolerated, with moderate
      myelosuppression as the main dose-limiting toxicity. CONCLUSIONS: The current
      combination regimen of leucovorin-modulated 5-FU with carboplatin is well
      tolerated with appropriate supportive care, produces significant objective
      responses in 21% of patients with biliary tree carcinoma, and should be
      considered for the treatment of this disease.

PMID- 9635524
TI  - Nonsteroidal antiinflammatory drug use and reduced risk of large bowel carcinoma.
AB  - BACKGROUND: Animal experiments and epidemiologic data have suggested that the use
      of nonsteroidal antiinflammatory drugs (NSAIDs) may decrease the incidence of
      large bowel carcinoma. Our purpose was to assess the relation of the use of
      aspirin and nonaspirin NSAIDs with the risk of large bowel carcinoma. METHODS: A
      population-based case-control study of colon and rectal carcinoma was conducted
      in Massachusetts from 1992 to 1994. Data on NSAID use and risk factors for large
      bowel carcinoma were collected by interview from 1201 incident cases of large
      bowel carcinoma and 1201 controls matched by age, gender, and area of residence.
      RESULTS: Regular NSAID use that continued into the year before diagnosis was
      associated with a significantly decreased relative risk estimate overall (0.7;
      95% confidence interval [CI], 0.5-0.8) and among Stage II-IV tumors (0.6; 95% CI,
      0.4-0.7). There was no reduction in risk for discontinued use. The inverse
      association with regular continuing use was present across age and gender and for
      both colon and rectal carcinoma. Similar inverse associations were present for
      regular continuing use of aspirin and nonaspirin NSAIDs. There was no significant
      evidence of a trend for the relative risk to decrease as the duration of use
      increased, nor was there a trend across the dose of aspirin, which ranged from
      less than one-half of a 325 mg tablet per day to > or = 2 tablets per day.
      Discontinuation of use in response to symptoms of carcinoma did not appear to
      explain the inverse association, nor did bias related to diagnosis of the
      carcinoma. CONCLUSIONS: These data add to the growing body of evidence that
      suggests a protective effect of NSAIDs against large bowel carcinoma.

PMID- 9635525
TI  - Epstein-Barr virus-associated nonsmall cell lung carcinoma: undifferentiated
      "lymphoepithelioma-like" carcinoma as a distinct entity with better prognosis.
AB  - BACKGROUND: Epstein-Barr virus (EBV) infection in nonsmall cell lung carcinoma
      (NSCLC) has been demonstrated in some ethnic groups. The pathobiology and the
      role of EBV and oncoprotein expression in these tumors have not been studied
      extensively. In this study, the authors investigated EBV-encoded RNA-1 (EBER1)
      transcripts by in situ hybridization and the expression of latent membrane
      protein-1 (LMP-1) and bcl-2 protein by immunohistochemistry in NSCLC patients
      from Taiwan, where nasopharyngeal carcinoma is endemic. METHODS: A total of 127
      cases of NSCLC (43 cases of squamous cell carcinoma [SCC], 67 cases of
      adenocarcinoma [AD], 12 cases of large cell carcinoma [LCC], and 5 cases of
      lymphoepithelioma-like carcinoma [LE]) were included. A sensitive polymerase
      chain reaction-derived, digoxigenin-labeled DNA probe for in situ detection of
      EBER1 transcripts was performed for the detection of EBV. Immunohistochemistry
      using the avidin-biotin-immunoperoxidase method was also performed to evaluate
      the expression of bcl-2 and LMP-1. RESULTS: EBER1 was detected in 11 of the 127
      NSCLC cases (8.7%; 6 SCC cases and 5 LE cases). All 5 LE cases were EBV-positive,
      whereas only 6 of the 43 SCC cases (14%), 0 of 67 AD cases, and 12 LCC cases were
      EBV-positive (P < 0.05). All five LE cases showed diffuse, strong, positive
      staining of tumor cells; five of the six SCC cases showed diffuse but weak
      staining. Among the nontumor epithelial cells, there was no EBER1 staining of any
      of the 11 EBER1-positive cases. The mean age of the LE patients was 10 years
      younger than that of the patients with other histological types. All 5 LE
      patients were nonsmokers, whereas 3 of the 6 patients with EBER1-positive SCC
      (50%) were smokers. EBER1 expression did not correlate with the 2-year survival
      rate of overall cases, but all 5 LE patients were alive without clinical evidence
      of disease at last follow-up. Gender, lymph node or distant metastasis, and
      clinical stage were not found to have any correlation with EBER1 expression (P >
      0.05). All LE cases had bcl-2 oncoprotein expression (100%). This frequency was
      significantly different from other histologic types (P < 0.05). The LMP-1
      detection rate was low and demonstrated no correlation with bcl-2 expression.
      CONCLUSIONS: In this study, the authors found that the primary LE of the lung is
      associated with young age, a history of not smoking, high bcl-2 immunoreactivity,
      and better survival rate. These characteristics demonstrate that EBV-associated
      LE of the lung is a unique entity. The findings of the current study suggest that
      EBV infection may play a different role in the tumorigenesis of primary LE of the
      lung than it does in other EBER1-positive NSCLCs.

PMID- 9635526
TI  - Relation between cellular doxorubicin binding ability to nuclear DNA and
      histologic response to preoperative chemotherapy in patients with osteosarcoma.
AB  - BACKGROUND: Although chemosensitivity to antiosteosarcoma agents is the most
      important prognostic factor in human osteosarcoma, none of the many
      chemosensitivity tests reported previously are reliable and clinically useful. In
      this study, the authors investigated the reliability and clinical availability of
      doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) binding assay (ABA) as
      a new chemosensitivity test for osteosarcoma. METHODS: Doxorubicin (adriamycin
      [ADM]) binding ability (%AB) to nuclear DNA in isolated osteosarcoma cells was
      assessed by ABA in 14 patients with primary osteosarcoma who were treated with
      preoperative chemotherapy containing ADM and 6 patients with relapsed
      osteosarcoma after intensive chemotherapy. Histologic responses to preoperative
      chemotherapy were evaluated by percentage of tumor necrosis (%necrosis). RESULTS:
      Four of the 14 patients with primary osteosarcoma had %AB > 80% (97.3+/-3.7%) and
      demonstrated good histologic responses (>90% of %necrosis) to preoperative
      chemotherapy, whereas the remaining 10 patients had %AB < 80% (38.9+/-21.0%) and
      demonstrated poor responses. Patients with recurrent osteosarcoma that was
      clinically evaluated to be resistant to previous chemotherapy also had low %AB
      (34.2+/-28.3%). CONCLUSIONS: Because the results of the current study revealed
      that ABA is useful for predicting chemosensitivity to chemotherapy with ADM as
      well as chemotherapy without ADM for patients with osteosarcoma, and because ABA
      technically is simple and results can be assessed rapidly, the authors conclude
      that ABA is a clinically useful chemosensitivity test for patients with
      osteosarcoma.

PMID- 9635527
TI  - Mesenchymal chondrosarcoma of the jaw bones: clinicopathologic study of 19 cases.
AB  - BACKGROUND: Patients with mesenchymal chondrosarcomas in general have a 5-year
      survival rate ranging from 42-54.6% and a 10-year survival rate of 28%. Nineteen
      cases of mesenchymal chondrosarcoma of the jaw bones were reviewed to study their
      clinicopathologic features and to compare their clinical behavior with that of
      mesenchymal chondrosarcomas of other locations. METHODS: The patients were 10
      males and 9 females (age range, 2-51 years). Sixteen patients were age < 30
      years, and the average age at presentation was 19 years. Eleven tumors involved
      the mandible and eight involved the maxilla. RESULTS: Histologically, the classic
      picture of a bimorphic tumor, composed of islands of well differentiated hyaline
      cartilage juxtaposed to a small cell undifferentiated malignancy, was present in
      every case. Resection, including hemimandibulectomy and hemimaxillectomy, was the
      main treatment in 16 patients. Seven patients had local recurrence, and five
      patients developed distant metastases. Six patients died of disease, and the 5
      year and 10-year survival rates were 82% and 56%, respectively. CONCLUSIONS:
      Mesenchymal chondrosarcoma of the jaw bones appears to have a more indolent
      course than mesenchymal chondrosarcoma of other anatomic

PMID- 9635528
TI  - Pathologic femoral fracture after periosteal excision and radiation for the
      treatment of soft tissue sarcoma.
AB  - BACKGROUND: Surgical resection and adjuvant radiation therapy are standard
      therapy for soft tissue sarcomas. When the tumor approximates bone, periosteal
      excision may be necessary. It was hypothesized that periosteal stripping and
      radiation therapy would increase the rate of pathologic fracture. METHODS: The
      soft tissue sarcoma data base at the Memorial Sloan-Kettering Cancer Center was
      used to identify a consecutive series of 205 patients who were treated over a 15
      year period (1982-1997). All patients had a soft tissue sarcoma of the thigh,
      which was managed by limb-sparing surgery and radiation therapy. Patients who had
      bone invasion by tumor or bone resection were not included. RESULTS: Nine
      patients, including eight women and one man, developed a femoral fracture in an
      area of previous radiation and surgery. All nine patients had undergone
      periosteal excision. The risk of fracture, by Kaplan-Meier survivorship, was 29%
      at 5 years if the resection included periosteum (P < 0.0001). Cox multiple
      regression analysis showed that periosteal excision was the only independent
      prognostic factor for the entire set of 205 patients at risk. However, for the
      subset of 54 patients who had periosteal stripping, two factors were also found
      to be prognostically important: female gender (P=0.022) and chemotherapy
      (P=0.020). The risk of fracture was 47% and 45%, respectively. The treatment of
      the fractures was difficult. There were four nonunions and three delayed unions.
      CONCLUSIONS: Periosteal stripping and radiation therapy places the femur at high
      risk of pathologic fractures, especially for female patients and patients
      undergoing chemotherapy. When practical, the combination of periosteal stripping
      and radiation should be avoided.

PMID- 9635529
TI  - Inflammatory breast carcinoma incidence and survival: the surveillance,
      epidemiology, and end results program of the National Cancer Institute, 1975
      1992.
AB  - BACKGROUND: Little is known about the cause of inflammatory breast carcinoma
      (IBC), the most aggressive form of breast cancer. To the authors' knowledge, no
      studies have investigated whether IBC risk factors are different from those for
      breast carcinoma overall, and there has been only one report of IBC incidence and
      survival patterns. METHODS: The authors used data from the Surveillance,
      Epidemiology, and End Results program of the National Cancer Institute for the
      period 1975-1992 to calculate age-adjusted incidence and survival rates for 913
      white and 121 African American women with IBC involving dermal invasion of
      lymphatic ducts and 166,375 white and 13,674 African American women with other
      types of breast carcinoma (non-IBC). RESULTS: Between 1975-1977 and 1990-1992,
      IBC incidence doubled, increasing among whites from 0.3 to 0.7 cases per 100,000
      person-years and among African Americans from 0.6 to 1.1 cases. However, rates
      for African Americans varied due to the small numbers of IBC cases. The twofold
      increase in IBC incidence was higher than that observed for non-IBC during the
      same period (27% for African Americans and 25% for whites). IBC patients were
      significantly younger at diagnosis than non-IBC patients; and among both IBC and
      non-IBC patients, African Americans were younger than whites. Overall survival
      was significantly worse for IBC patients than for non-IBC patients and for
      African Americans than for whites. Among whites, 3-year survival improved more
      for IBC patients than for non-IBC patients between 1975-1979 and 1988-1992,
      increasing from 32% to 42% for IBC patients (P=0.0001) and from 80% to 85% for
      non-IBC patients (P=0.0001). CONCLUSIONS: The disparities observed in incidence
      trends and age at diagnosis, particularly according to race, highlight the need
      for further investigation of the differences between IBC and non-IBC incidence.

PMID- 9635530
TI  - The extent of proliferative and apoptotic activity in intraductal and invasive
      ductal breast carcinomas detected by Ki-67 labeling and terminal deoxynucleotidyl
      transferase-mediated digoxigenin-11-dUTP nick end labeling.
AB  - BACKGROUND: The balance among cell proliferation, cell differentiation, and cell
      death determines the cell number in a population as well as the size or even the
      stage of a tumor. Thus, to improve our understanding of the pathogenesis of
      neoplasms, it is important to investigate the regulation of both cell
      proliferation and cell death. METHODS: This study examined the occurrence of
      apoptosis and proliferative capacity in 46 breast carcinomas: 20 intraductal
      carcinomas (ductal carcinomas in situ [DCIS]) and 26 infiltrative ductal
      carcinomas (IDC). Terminal deoxynucleotidyl transferase-mediated digoxigenin-11
      dUTP nick end labeling (TUNEL) and immunostaining with the Ki-67 antibody were
      used in the examination. A ladder of DNA fragments induced by apoptosis was
      demonstrated by means of DNA agarose gel electrophoresis in 10 of the available
      TUNEL positive and negative samples. RESULTS: The results were correlated with
      p53, bcl-2, estrogen receptor (ER), and progesterone receptor (PR) protein
      expression, which would suggest association with apoptosis by
      immunohistochemistry. The apoptosis and proliferation of each cancer were
      expressed as the number of tumor cells undergoing apoptosis and proliferation per
      1000 tumor cells. The extent of apoptosis was more frequently observed in DCIS
      than in IDC (21.9+/-6.8 vs. 4.0+/-0.9, P < 0.001), and the proliferation activity
      was significantly higher in IDC than in DCIS (16.8+/-6.5 vs. 3.5+/-0.8, P <
      0.006). Apoptosis associated with MIB-1 positive cells and TUNEL labeling was
      significantly higher in IDC than in DCIS (3.26 vs. 0.42, P=0.001). In DCIS,
      apoptosis was correlated with p53 (r=0.663, P=0.005), and p53 had a reverse
      correlation with bcl-2 (r=0.620, P= 0.018). Moreover, bcl-2 expression was
      associated with ER (P=0.028) and PR (P= 0.005) expression in both DCIS and IDC.
      CONCLUSIONS: The results of this study show that a higher degree of apoptosis and
      lower proliferation activity in intraductal carcinoma result in a steady-state,
      self-renewing condition in which net growth of the tumor is rare. The results
      also indicate that apoptosis was altered by the expression of p53, bcl-2, ER, and
      PR.

PMID- 9635531
TI  - Mammary ductal carcinoma in situ with microinvasion.
AB  - BACKGROUND: The natural history of patients with intraductal carcinoma (DCIS) and
      microinvasion is poorly defined, and the clinical management of these patients,
      with particular reference to management of the axilla, has been controversial.
      Previous studies of this lesion have used varied and/or arbitrary criteria for
      the evaluation of microinvasion. METHODS: Thirty-eight DCIS lesions with
      microinvasion (n=29) or probable microinvasion (n=9), diagnosed during the period
      1980-1996, were retrospectively analyzed after cases not treated with mastectomy
      and axillary lymph node dissection were excluded. Microinvasion was defined as a
      single focus of invasive carcinoma < or = 2 mm or up to 3 foci of invasion, each
      < or =1 mm in greatest dimension. RESULTS: The patients were all females with a
      mean age of 56.4 years. DCIS was of comedo (n=31) or papillary (n=7) subtype.
      Microinvasion was often associated with an altered, desmoplastic stroma (55%) or
      a lymphocytic infiltrate (39%). The foci of microinvasion ranged from 0.25 to
      1.75 mm (mean, 0.6 mm), with an aggregate mean size of 1.1 mm (range, 0.25-2.25
      mm). Foci of microinvasion, ranging from 1 to 3 (mean, 1.7), were adjacent to
      DCIS in 95.3% of cases. The extent of DCIS did not correlate with the number of
      foci of microinvasion. Axillary lymph node dissections yielded a mean of 19.3
      lymph nodes (range, 7-38), and all lymph nodes were negative for metastasis. None
      of 33 patients, followed for a mean of 7.5 years (range, 1.0-14.4 years),
      developed local recurrence or metastasis. CONCLUSIONS: The cases of microinvasive
      carcinoma examined in this study, as defined above, were not associated with
      axillary lymph node metastases and appeared to be associated with an excellent
      prognosis. Further study is indicated to determine the appropriate management and
      long term prognosis of patients with this lesion.

PMID- 9635532
TI  - How reminders given to patients and physicians affected pap smear use in a health
      maintenance organization: results of a randomized controlled trial.
AB  - BACKGROUND: Despite its effectiveness as a method of controlling cervical
      carcinoma, the use of Pap smear testing remains incomplete, and its promotion in
      the primary care setting provides an important opportunity for intervention.
      METHODS: The authors conducted a randomized controlled trial that involved three
      sites of a health maintenance organization (HMO) serving an urban minority
      population. Their aim was to evaluate the impact of reminders given to patients
      and physicians on site visitation by patients and Pap smear use. Eligible women
      (n=5801) were randomly assigned to 1 of 4 intervention combinations (in which
      reminders were given to either the patient or the physician, to both, or to
      neither). If they were ineligible for patient reminder intervention, patients
      were randomized only to physician reminder intervention (the presence or absence
      of it). The letter of reminder mailed to the patient invited women due for Pap
      smears to visit the HMO site, and the reminder for physicians was a medical
      record notice that a Pap smear was due. Logistic and survival analyses were used
      to investigate the correlation of intervention status with visitation, interval
      of time to a visit, and Pap smear use. RESULTS: In the primary intent-to-treat
      analysis, there was no significant effect of either patient or physician reminder
      interventions on rates of visitation or Pap smear completion. The secondary
      efficacy analyses demonstrated no overall effect of either patient or physician
      reminders, but effects among subgroups of women at individual HMO sites were
      noted. At Site 3, there was an apparent increase in time to the next visit among
      the subgroup of women with a chronic illness (16 weeks with intervention vs. 9
      weeks without). With the physician reminder, the odds that a Pap smear would be
      given during the study year were increased among women without a previous Pap
      smear at Site 1 (adjusted odds ratio=1.39) and those with a chronic illness at
      Site 2 (adjusted odds ratio=3.38). CONCLUSIONS: Reminders given to patients and
      physicians had a limited impact on visitation by patients to the HMO sites or Pap
      smear completion. Although some subgroups of women may benefit, the authors also
      observed a possibly unfavorable impact among other subgroups. These results
      emphasize the importance of identifying more effective interventions, targeting
      them to women most likely to benefit, and not overlooking the possibility that
      preventive intervention will have an unanticipated adverse effect.

PMID- 9635533
TI  - Squamous intraepithelial lesions of the cervix, invasive cervical carcinoma, and
      immunosuppression induced by human immunodeficiency virus in Africa. Dyscer-CI
      Group.
AB  - BACKGROUND: Squamous intraepithelial lesions (SILs) of the cervix are associated
      with human immunodeficiency virus (HIV) infection, but multiple risk factors must
      be considered in this context. The authors performed a cross-sectional study to
      assess the prevalence of and the factors associated with SILs and invasive
      cervical carcinoma (ICC). METHODS: In Abidjan, Cote d'Ivoire, women were
      recruited from three outpatient gynecology clinics and screened for both cervical
      disease and HIV infection. A CD4 cell count was performed for HIV-infected women.
      RESULTS: A total of 2198 women were included in the study. The prevalence of HIV
      infection was 21.7%. Of the 2170 women who underwent a cervical screening, 254
      (11.7%) presented with a dysplasia or neoplasia: 7.6% had low grade SILs (LSILs),
      3.3% had high grade SILs (HSILs), and 0.8% had ICCs. In multivariate analyses,
      factors associated with these lesions were as follows: for LSILs, HIV-1
      seropositivity, age <24 years, parity >1, consultation for genital infection, and
      no use of oral contraception in the past; for HSILs, HIV-1 seropositivity,
      chewing tobacco use, low educational level, and parity >1; and for ICCs, age >33
      years, parity >3, and illiteracy. In women infected with HIV-1, the prevalence of
      LSILs increased with a decrease in CD4 cell count, whereas this relation was not
      found among patients with HSILs. ICCs were linked to HIV-2 infection, but not to
      HIV-1 infection, in univariate analysis. CONCLUSIONS: In Africa, the prevalence
      of SILs is high. The factors associated with precancerous and cancerous lesions
      are different. Cancers in women infected with HIV-1 often may not reach the
      invasive stage. These findings could have implications for cervical screening
      programs in the future.

PMID- 9635534
TI  - Expression of p21WAF1/CIP1 in adenocarcinoma of the uterine cervix: a possible
      immunohistochemical marker of a favorable prognosis.
AB  - BACKGROUND: The purpose of this study was to assess the prognostic significance
      of the expression of estrogen receptor and cell cycle regulatory gene products in
      cervical adenocarcinoma. METHODS: In 40 cases of adenocarcinoma of the uterine
      cervix and 10 normal cervices, expression of estrogen receptor and cell cycle
      regulatory gene products (cyclin E, p16, p21WAF1/CIP1, p27, p53, and Ki-67) was
      studied using immunohistochemical techniques. The survival of the patients was
      analyzed in terms of such variables as the expression of these molecules in the
      tumor and conventional clinicopathologic features, and the Cox proportional
      hazards model was used to predict the survival of patients with cervical
      adenocarcinoma. RESULTS: Expression of estrogen receptor was consistently
      observed in normal cervical glands, but in cervical adenocarcinoma it was lost
      (in 28 cases) or significantly diminished (in 12 cases). Normal cervical
      glandular cells were usually negative for the cell cycle regulatory gene
      products, whereas 47.5-85% of cervical adenocarcinomas were positive for these
      molecules. When the expression of these molecules was analyzed, significant
      positive correlations were found between p16 and p27, cyclin E and p27, and
      cyclin E and p21WAF1/CIP1. Univariate survival analysis revealed that the
      presence of parametrial invasion, the presence of lymph node metastasis, negative
      staining for p21WAF1/CIP1, and a moderately or poorly differentiated tumor all
      correlated significantly with a poor prognosis. In a stepwise regression
      analysis, the expression of p21WAF1/CIP1 and negative pelvic lymph nodes were the
      best predictors of a favorable prognosis. CONCLUSIONS: Expression of p21WAF1/CIP1
      correlated with a favorable prognosis for patients with cervical adenocarcinoma
      and may serve as a useful marker of survival in cases of this disease.

PMID- 9635535
TI  - Interstitial fluid pressure in cervical carcinoma: within tumor heterogeneity,
      and relation to oxygen tension.
AB  - BACKGROUND: Interstitial fluid pressure (IFP) is elevated in many animal and
      human tumors. The authors assessed tumor IFP and its relation to tumor
      oxygenation in a prospective clinical study of patients with cervical carcinoma.
      METHODS: Measurements were made in 77 patients with cervical carcinoma prior to
      treatment. IFP was measured in normal paravaginal submucosal tissue and at one to
      five positions in the visible tumor with the patients anesthetized and in the
      lithotomy position. Tumor oxygen tension was measured immediately prior to IFP
      using a polarographic needle electrode. Patients were treated with radiotherapy
      only. Response was evaluated 3 months after the completion of radiotherapy.
      RESULTS: There was substantial variation in IFP from region to region in some
      tumors. The mean IFP in individual tumors ranged from 3 to 48 millimeters of
      mercury (mmHg). The overall mean and median values for the entire patient group
      were 19 mmHg and 17 mmHg, respectively. IFP was significantly higher in tumor
      tissue than in normal tissue (P < 0.0001). Tumors with high IFP were more likely
      to be hypoxic (P < 0.007) and less likely to regress completely with radiotherapy
      (P < 0.04). CONCLUSIONS: IFP in cervical carcinoma is elevated above normal
      tissue values. Multiple measurements are needed to evaluate IFP in these tumors.
      High IFP is associated with hypoxia and may provide information about the
      mechanism of hypoxia on which treatment can be based.

PMID- 9635536
TI  - Cystic embryonal sarcoma of kidney: a case report.
AB  - BACKGROUND: Morphologic analysis of malignant renal tumors of childhood and
      adolescence has resulted in the identification of a variety of tumor types with
      characteristic histology and clinical behavior. The authors report a case of
      renal sarcoma in a 19-year-old male that differs in morphology from the various
      established categories of primitive renal tumors. METHODS: Sections taken from
      the nephrectomy specimen were stained by routine methods and by
      immunohistochemistry for stromal and epithelial markers, and for proliferation
      markers. In addition, ultrastructural studies were undertaken. RESULTS: The
      tumor, which the authors termed cystic embryonal sarcoma, was comprised of poorly
      differentiated malignant mesenchyme in a myxoid stroma. Numerous epithelial-lined
      cysts were present. The distribution of the cysts and proliferation kinetics of
      cyst-lining epithelial cells suggested that they were derived from entrapped
      renal tubules. The tumor showed early recurrence postoperatively and after
      aggressive chemotherapy. The pathologic features and clinical behavior of the
      tumor resemble those of 2 previously reported cases and an additional 25 cases
      from the files of the National Wilms' Tumor Study Pathology Center. CONCLUSIONS:
      The clinical and histologic features of cystic embryonal sarcoma differ from
      those of other renal tumors of childhood and adolescence, and the tumor appears
      to be a novel form of renal malignancy.

PMID- 9635537
TI  - Plasma glutathione S-transferase P1-1 levels in patients with head and neck
      squamous cell carcinoma.
AB  - BACKGROUND: Many tumors contain high amounts of the detoxification enzyme
      glutathione S-transferase P1-1 (GSTP1-1). Elevated levels of GSTP1-1 have also
      been detected in serum and plasma from patients with gastrointestinal, lung, or
      head and neck tumors. The authors of this report evaluated the role of GSTP1-1 as
      a plasma tumor marker in patients with head and neck squamous cell carcinoma
      (HNSCC) of the larynx, hypopharynx, or oropharnyx and in patients with benign
      head and neck lesions (BHNL). METHODS: GSTP1-1 levels were measured in EDTA
      plasma combined with ethylenediaminetetraacetic acid using a recently developed
      sensitive and specific sandwich enzyme-linked immunoadsorbent assay. A normal
      reference level with an upper limit of 21.8 microg GSTP1-1 per liter of plasma
      was calculated from results obtained with samples from 230 blood donors. RESULTS:
      Median GSTP1-1 levels in samples from 53 patients with oral/oropharyngeal SCC
      (10.6 microg/L; range, 3.7-46.1 microg/L), 12 patients with hypopharyngeal SCC
      (11.9 microg/L; range, 5.2-146.6 microg/L), and 28 patients with laryngeal SCC
      (14.4 microg/L; range, 6.4-141.5 microg/L) were significantly elevated when
      compared with plasma GSTP1-1 levels in samples from 45 patients with BHNL (8.1
      microg/L; range, 3.3-32.3 microg/L; P < 0.0001, P < 0.01, and P < 0.0001,
      respectively). However, only 6 of 53 patients (11%) with oral/oropharyngeal SCC,
      1 of 12 patients (8%) with hypopharyngeal SCC, and 6 of 28 patients (21%) with
      laryngeal SCC had plasma GSTP1-1 levels above the upper limit of the normal
      reference level. Thus, only 13 of 93 patients (14%) with HNSCC had elevated
      plasma GSTP1-1 levels overall. No significant relation between plasma GSTP1-1
      levels and TNM classification of the tumors was observed. CONCLUSIONS: GSTP1-1 is
      not a suitable plasma tumor marker for HNSCC.

PMID- 9635538
TI  - Application of the international prognostic index in a study of Chinese patients
      with non-Hodgkin's lymphoma and a high incidence of primary extranodal lymphoma.
AB  - BACKGROUND: Chemotherapy containing anthracycline is the standard initial
      treatment for aggressive non-Hodgkin's lymphoma (NHL), and the International
      Prognostic Index (IPI) is widely accepted as the standard tool for determining
      the prognosis of patients with this disease. However, the data on which the IPI
      was based primarily came from studies conducted in Western countries. It may not
      be directly applicable to Asian populations, in which the incidence of primary
      extranodal lymphoma (PENL) is known to be high. METHODS: The authors conducted a
      retrospective study of 218 patients with aggressive NHL who were treated with
      chemotherapy. They analyzed the distribution of stage and pathology, prognostic
      factors, toxicity, and treatment outcome. The IPI was then applied and its
      ability to identify distinct prognostic groups tested. RESULTS: Eighty-six
      patients (39.4%) had lymph node lymphoma (LNL) and 132 (60.6%) had primary
      extranodal lymphoma (defined as non-Hodgkin's lymphoma with primary presentation,
      bulk of disease, and histologic confirmation at an extranodal site). The most
      common primary extranodal sites were the stomach (22%) and Waldeyer's tonsillar
      ring (18.9%). The complete response rate of PENL patients to chemotherapy
      containing anthracycline was 52%, as compared with 64% of the LNL group. The 5
      year survival rates for patients with LNL and PENL were 57.4% and 52.1%,
      respectively. The toxicity in the two patient groups was similar. Four of the
      prognostic factors in the IPI-age, serum LDH, performance status, and disease
      stage-predicted significantly different survival for PENL and LNL patients.
      However, the number of extranodal sites involved was not a significant predictive
      variable in PENL. CONCLUSIONS: The IPI was applicable to this Chinese population
      in which the incidence of PENL was high, although the number of extranodal sites
      did not achieve statistical significance as a risk factor. A proposal for
      modification was made. Chemotherapy containing anthracycline was an effective
      treatment for both PENL and LNL patients.

PMID- 9635539
TI  - How should imipenem-cilastatin be used in the treatment of fever and infection in
      neutropenic cancer patients?
AB  - BACKGROUND: Imipenem-cilastatin (referred to hereafter as imipenem) is
      administered at different doses as monotherapy or with other agents. Limited
      comparisons of the alternatives exist. The authors compared the efficacy and
      safety of several imipenem-containing regimens (ICRs) to determine the
      appropriate dose and the need for combination therapy. METHODS: Between 1985 and
      1994, febrile neutropenic patients were given ICRs according to the same
      methodology on prospective trials at a referral cancer center. The ICRs were high
      dose imipenem (HIP), high dose imipenem and amikacin (HIPA), high dose imipenem
      and vancomycin (HIPV), and low dose imipenem and vancomycin (LIPV). RESULTS: The
      overall response rates were comparable (70-77%). There was a univariate trend
      toward better response among patients with pneumonia and documented infections
      with unidentified organisms who received HIPV versus LIPV (P=0.06), as well as a
      significantly better response among patients with gram positive infections who
      received HIPV versus HIP (P=0.02) and HIPA (P=0.002). HIPV was a more effective
      treatment for documented infections with identified organisms (P=0.05) and
      bloodstream infections (P=0.04) than HIP; there was a univariate trend toward
      better response among patients infected with gram negative organisms who received
      HIPA versus HIP (P=0.12). Multivariate adjustment for baseline and prognostic
      factors did not reveal a relative advantage for any regimen. No differences in
      overall toxicities were observed between HIPV and LIPV. CONCLUSIONS: Imipenem
      monotherapy is adequate treatment for most febrile neutropenic cancer patients.
      Low dose imipenem could be effective and safe in uncomplicated cases without
      pneumonia. Further studies are needed to establish the usefulness of low dose
      imipenem in this context.

PMID- 9635540
TI  - MIB-1 labeling index in nonpilocytic astrocytoma of childhood: a study of 101
      cases.
AB  - BACKGROUND: The prognosis of pediatric patients with nonpilocytic astrocytoma,
      and in particular those with anaplastic astrocytoma, is somewhat unpredictable.
      This study used MIB-1 monoclonal antibody, a proliferative marker that can be
      used in formalin fixed paraffin embedded tissues, to study nonpilocytic pediatric
      astrocytoma. METHODS: Astrocytoma, anaplastic astrocytoma, and glioblastoma
      specimens excised from a total of 101 pediatric patients during the period from
      January 1975 to September 1996 were retrieved from the authors' surgical
      pathology file. Histologic grading of the specimens was performed based on a
      modified Ringertz system. The proliferative potential of the tumors was estimated
      by using the MIB-1 labeling index (LI), which was evaluated with morphologic
      grades of tumors and survival of the patients. RESULTS: Of the 101 patients, 34
      had astrocytoma, 33 had anaplastic astrocytoma, and 34 had glioblastoma. Their
      mean survival times were 165.2+/-14.9 months (mean+/-standard error; SE), 46.1+/
      9.9 months, and 21.8+/-5.6 months, respectively. The mean MIB-1 LI of different
      tumor grades were as follows: astrocytoma, 3.9+/-4.3 (mean+/-standard deviation;
      range, 0.0-21.6); anaplastic astrocytoma, 24.3+/-15.6 (range, 1.7-62.8); and
      glioblastoma, 35.9+/-16.4 (range, 7.36-63.3). The mean survival of the entire
      group of patients with LIs < or = 11 was 173.2+/-12.2 months (mean+/-SE), and the
      mean survival of those with LIs > 11 was 20.3+/-4.1 months. The survival of
      anaplastic astrocytoma patients with LIs < or = 11 was similar to that of
      astrocytoma patients, whereas the survival of anaplastic astrocytoma patients
      with LI > 11 was similar to that of patients with glioblastoma. CONCLUSIONS: The
      results of the current study show that histopathologic grading can predict the
      outcome for patients with astrocytomas and glioblastomas, whereas MIB-1 LI can
      separate better and worse prognostic groups in patients with anaplastic
      astrocytoma.

PMID- 9635541
TI  - Informed consent in the Childrens Cancer Group: results of preliminary research.
AB  - BACKGROUND: Informed consent is critical to the ethical conduct of pediatric
      cancer clinical research. Research regarding such consent has been limited.
      METHODS: After conducting a background survey of institutional practice from
      principal investigators (PIs) at 113 Childrens Cancer Group (CCG) centers, the
      authors obtained more detailed data regarding informed consent from 23 parents of
      children recently enrolled in CCG research trials and from 23 clinician
      investigators at 5 CCG institutions. RESULTS: Approximately 73% of PIs responded
      to the background survey, providing context in which to interpret the more
      detailed information. Parents reported that they found the informed consent
      process helpful, although somewhat confusing. Satisfaction with informed consent
      was not related to ethnicity or education level. Parents found discussion with
      staff more helpful than the consent document, and the majority reported that the
      amount of information conveyed was appropriate. Although only 3 parents (13%)
      reported that too much information was given, nearly 50% of the investigators
      believed too much information usually is provided. All investigators believed
      that patients benefit from participation in CCG studies; the majority recommend
      that the child be enrolled on study, and the majority believe the major obstacle
      to good informed consent is parents' "state of shock." CONCLUSIONS: Parents
      expressed general satisfaction with the consent process. By contrast, clinician
      responses indicate dissatisfaction with the informed consent process. Future
      research must include more centers and larger numbers of parents of children who
      we enrolled as well as those who declined to participate in CCG studies, examine
      consent in minority subgroups, and further investigate the role of clinician
      investigators and their interaction with parents and children during the informed
      consent process.

PMID- 9635542
TI  - Introduction: augmentation of antidepressant medication.

PMID- 9635543
TI  - Treating antidepressant nonresponders with augmentation strategies: an overview.
AB  - This paper provides an overview of antidepressant nonresponse and the role of
      augmentation strategies in the management of treatment-resistant depression. When
      effective, the more widely used augmentation strategies, including lithium salts,
      thyroid hormones, pindolol, buspirone, and psychostimulants, share two important
      advantages when compared with "switching" strategies: avoidance of ill effects
      associated with discontinuing the initial antidepressant and rapidity of onset of
      action. Ideally, advances in the understanding of the neurobiology of mood
      disorders and mechanisms of antidepressant response will permit a more efficient
      and specific matching between patient, initial antidepressant, and subsequent
      strategy for enhancing response to treatment.

PMID- 9635544
TI  - The use of pindolol to potentiate antidepressant medication.
AB  - Serotonin (5-HT) selective reuptake inhibitors (SSRIs) and monoamine oxidase
      inhibitors are thought to have a delayed onset of antidepressant action
      attributable in part to the decrease in firing activity of 5-HT neurons they
      produce upon treatment initiation. As cell body 5-HT1A autoreceptors desensitize,
      5-HT neuronal firing is restored. The agent pindolol, through its 5-HT1A receptor
      blocking property, has been shown to prevent the initial decrease in firing of
      rat 5-HT neurons associated with SSRI treatment. Four open-label studies put into
      evidence a significant acceleration of the antidepressant effect of SSRIs when
      combined with pindolol. Four of five placebo-controlled studies have confirmed
      this observation. Controlled trials indicate that a greater rate of response may
      be obtained by combining pindolol from the beginning of the SSRI treatment. The
      strategy of adding pindolol to the regimen of SSRI-resistant patients also
      appears to produce a therapeutic effect in a significant proportion of patients.

PMID- 9635545
TI  - The use of thyroid supplements to augment antidepressant medication.
AB  - Despite methodological flaws that limit conclusions, a considerable database
      documents the efficacy of triiodothyronine (T3) as an augmentation strategy for
      response to various classes of antidepressants. One study suggests that T3 and
      lithium are of comparable efficacy in antidepressant nonresponders. No clear
      biochemical or clinical predictors of preferential response to T3 have been
      found. The role of T3 augmentation requires further evaluation, especially with
      regard to dose and duration.

PMID- 9635546
TI  - The use of lithium to augment antidepressant medication.
AB  - Lithium is one of the most studied agents used to augment the pharmacologic
      effect of antidepressant drugs, particularly in refractory depression. We
      reviewed 22 case reports, 22 open trials, 5 open comparison studies, and 9
      placebo-controlled studies of lithium augmentation and 6 studies in which
      antidepressants were added to, or coadministrated with, lithium. The efficacy of
      the augmentation therapeutic strategy is supported by these analyses, involving
      969 patients. The optimal dose and the most effective blood levels of lithium are
      unclear, but a reasonable strategy would be to start with low doses (600-900
      mg/day) and, if necessary, to increase the doses to obtain a level in accordance
      with the usual therapeutic range of blood levels (0.8-1.2 mEq/L). Some patients
      respond quickly, but others need a long and combined treatment; it is thus
      advantageous to prescribe lithium for at least 3 to 6 weeks. Despite the fact
      that the mechanism of action of lithium augmentation is still unknown, all
      refractory depressed patients can potentially be treated by lithium augmentation,
      particularly bipolar patients, to obtain full prophylactic effect as soon as
      possible.

PMID- 9635547
TI  - Anxiolytic antidepressant augmentation.
AB  - The administration of anxiolytic drugs often accompanies treatment with
      antidepressant medications. Although benzodiazepines help alleviate the secondary
      depressive symptoms of anxiety and sleep disturbance, they do not actually
      enhance antidepressant response. On the other hand, the anxiolytic agent
      buspirone does facilitate direct antidepressant response, largely through its
      ability to activate both presynaptic and postsynaptic 5-HT1A receptors and thus
      modulate serotonin release. Several case studies and open-label trials have
      demonstrated the effectiveness of buspirone as an augmentation agent. Because
      buspirone is also associated with few adverse effects, it appears to be both
      effective and safe in the augmentation of antidepressant pharmacotherapy.

PMID- 9635548
TI  - The use of anticonvulsants to augment antidepressant medication.
AB  - Combination therapy that couples classical antidepressants with other
      psychoactive compounds is one of the major therapeutic strategies in therapy
      resistant depression. The authors review reports on the antidepressive effects of
      the mood stabilizers carbamazepine and valproate and focus on the pharmacodynamic
      and clinical aspects of combining these compounds with antidepressant drugs. In
      addition, a pivotal study (N=10 outpatients) demonstrates the use and efficacy of
      a low-dose combination therapy of carbamazepine and amitriptyline. It is
      concluded that low-dose combination of classical antidepressants and mood
      stabilizers appears to be well tolerated and highly effective.

PMID- 9635549
TI  - Dopaminergic agents and stimulants as antidepressant augmentation strategies.
AB  - Dopaminergic agents and stimulants have been used to manage depression when
      conventional antidepressant treatments fail. We reviewed evidence for the role of
      dopaminergic dysfunction in depression, the use of dopaminergic agents as
      antidepressants, and the use of dopaminergic agents and stimulants as
      antidepressant adjuncts. Dopamine may be part of the pathophysiology of
      depression for a subset of patients. When used with caution and an appreciation
      of the potential risk of abuse, dopaminergic agents and stimulants may be useful
      for patients refractory to antidepressants alone.

PMID- 9635550
TI  - Augmentation strategies with serotonergic-noradrenergic combinations.
AB  - Combinations of antidepressants with both serotonergic and noradrenergic activity
      may be especially effective and thus useful in treating refractory patients and
      severely depressed patients. In the current report, studies of combinations of
      serotonin selective reuptake inhibitors (SSRIs) and noradrenergic tricyclics or
      of SSRIs and bupropion are reviewed, and practical issues pertaining to their use
      are discussed.

PMID- 9635551
TI  - Antidepressant augmentation: conclusions and recommendations.

PMID- 9635552
TI  - A few comments on RSD (reflex sympathetic dystrophy)

PMID- 9635553
TI  - Kinematic analysis of patients with spinal muscular atrophy during spontaneous
      breathing and mechanical ventilation.
AB  - Patients with infantile spinal muscular atrophy develop pectus excavatum along
      with a severe restrictive syndrome as a result of failure to expand the upper
      chest wall and lungs because of intercostal muscle weakness. By using an
      automatic motion analyzer to provide three-dimensional computer analyses of
      images sampled at 25 Hz, 9 spinal muscular atrophy Type II patients and 13
      controls underwent kinematic analysis of thoracoabdominal movements partitioned
      into the upper thorax, lower thorax, and abdominal volume compartments. The
      analyses were performed during spontaneous breathing for the controls and during
      spontaneous breathing and while using mechanically assisted ventilation for the
      patients. Vital capacity, maximum inspiratory pressures, and nocturnal
      oxyhemoglobin saturation and transcutaneous carbon dioxide tensions were also
      measured for the patients. The kinematic data demonstrated a paradoxical
      ventilatory pattern for the spontaneously breathing SMA patients with the
      following inspiratory volume changes: upper thorax, -6.4+/-9.6%; lower thorax,
      7.3+/-15.8%; abdominal, 99.1+/-21.3%. During mechanical ventilation, the
      compartmental volume changes were as follows: upper thorax, 13.5+/-6%; lower
      thorax, 13.7+/-7.9%; abdominal, 72.7+/-9.3%. This kinematic pattern is comparable
      with that seen in spontaneously breathing normal subjects. We conclude that
      mechanical ventilation can normalize kinematic volume changes during alveolar
      ventilation and that this might help deter loss of thoracic compliance caused by
      the chronic hypoventilation of the upper thoracic compartments. Kinematic
      analysis may be helpful for choosing the ventilation parameters to optimize
      therapeutic benefits.

PMID- 9635554
TI  - Outcome, efficiency, and time-trend pattern analyses for stroke rehabilitation.
AB  - We present a series of pattern analysis techniques using inpatient medical
      rehabilitation as an example setting, stroke as a model diagnosis, and various
      versions of the Functional Independence Measure-Function Related Groups as a case
      mix adjuster. The pattern analytic approach uses severity-adjusted benchmarks to
      distinguish among groups of patients whose outcomes and resource use patterns are
      lower, typical, or higher than established ranges at set points in treatment.
      Changing outcome and resource use patterns were illustrated for 1990, 1992, and
      1995 discharges (n=34,734). These pattern analytic approaches are applicable to
      any postacute care rehabilitation setting, assuming the availability of an
      appropriate case mix adjuster and a reliable patient information system. These
      techniques provide clinicians with tools to help maintain quality in this era of
      managed care.

PMID- 9635555
TI  - Predicting follow-up functional outcomes in outpatient rehabilitation.
AB  - Functional outcomes at an average of six months after outpatient rehabilitation
      were investigated in a pilot study with a sample of 42 patients receiving
      physical therapy for low back, neck, and other musculoskeletal problems. Logistic
      regression analyses were used to study variables related to the achievement of a
      predetermined level of physical functioning or to whether improvement occurred
      from initial to follow-up assessment. Scales used in the analyses were obtained
      from two measures of functioning, the Medical Outcomes Trust Short Form 36 (SF
      36) and the Medical Rehabilitation Follow Along (MRFA instrument). Demographic
      and program characteristic variables obtained from clinic records were also
      included in the analyses. The independent variables entered into two groups of
      regression equations included age, gender, presenting problem, workers'
      compensation coverage, functioning at initial assessment, number of visits,
      length of program, and intensity of program. For the SF-36, the General Health
      scale and presenting problem predicted above or below a level greater than one
      standard deviation less than the mean on the Physical Functioning scale at follow
      up. The combination of the Role Physical and Role Emotional scales predicted
      follow-up level on the Physical Component Summary (PCS) scale. The interaction of
      age and intensity of treatment was predictive for both the Physical Functioning
      and PCS scales. For predicting improvement or no improvement using the SF-36
      scales, General Health and the interaction between age and intensity were
      predictive of change on the Physical Functioning scale, whereas age and the
      interaction between age and number of visits were predictive of change on the PCS
      scale. For the MRFA instrument, the interaction between age and the intensity of
      treatment was predictive for both a predetermined level of physical functioning
      and amount of improvement in physical functioning at follow-up. An intensity
      rating of pain and a measure of affective distress at initial assessment both
      improved the identification of patients at risk for not reaching a given level of
      functioning, whereas treatment intensity improved the identification of those
      patients at risk for not showing improvement at follow-up. Length of time between
      the end of outpatient therapy and follow-up assessment was generally not related
      to follow-up physical functioning. Interpretation and implications of these
      findings, as well as applications of this analytic approach to outcomes
      assessment, are discussed.

PMID- 9635556
TI  - Effectiveness of force application in manual wheelchair propulsion in persons
      with spinal cord injuries.
AB  - The objective of this study was to investigate effectiveness of force
      application, the ratio power output/energy expenditure, and timing parameters of
      wheelchair propulsion in persons with tetraplegia (TP, n=17) and paraplegia (PP,
      n=12), at two different intensity conditions. All subjects performed a maximal
      exercise test on a wheelchair ergometer. Exercise bouts with an intensity of 30
      to 50% and 60 to 80% of the maximal power output were analyzed. Effectiveness of
      force application, defined as the ratio of the effective force and the total
      force, was considerably lower in TP, compared with PP. Effectiveness of force
      application in the plane of the wheel was comparable between TP and PP. TP showed
      a significantly lower effectiveness of force application in the frontal plane and
      applied the forces in a more lateromedial direction to the hand rim. The ratio
      power output/energy expenditure, calculated as an indication of gross mechanical
      efficiency, was considerably lower in TP and was associated with the
      effectiveness of force application (r=0.64; P < 0.01). Timing parameters showed
      that TP positioned their hands in a more backward position on the hand rim.
      Comparing the different intensity conditions revealed that force was applied more
      effectively, and the ratio power output/energy expenditure was higher at the
      higher intensity condition. Push time, relative to cycle time, increased, and
      beginning angle showed a forward shift with a higher load. TP tended to decrease,
      whereas PP showed a tendency for an increase in stroke angle with a higher load.
      The low effectiveness and different pattern of force application in TP should be
      taken into account when developing other wheelchair propelling mechanisms and
      training programs for this population.

PMID- 9635557
TI  - Propulsion technique and anaerobic work capacity in elite wheelchair athletes:
      cross-sectional analysis.
AB  - Wheelchair sports and daily manual wheelchair propulsion are dominated by
      frequent short-term power demands. The purpose of the current cross-sectional
      study was to determine the variation in propulsion technique in association with
      sprint power production among elite wheelchair athletes. Therefore, 67 wheelchair
      athletes (different impairments; 17 female and 50 male athletes; age, 29.1+/-7
      yr; body weight, 60.7+/-11.8 kg; training hours, 12.9+/-6.4 h x wk(-1); VO2 peak,
      1.7+/-0.7 liter x min(-1); aerobic power output, 72.2+/-36.7 W) were studied
      during the World Championships and Games for the Disabled in Assen (1990) on
      propulsion technique and anaerobic work capacity in a 30-s sprint test on a
      computer controlled wheelchair ergometer. Mean power output (P30) (97+/-45.8 W;
      range, 8.3-195.3 W) and heart rate (158.6+/-23.6 b x min(-1)) were highly
      variable and seemed associated with impairment level: track athletes, classified
      in four different functional classes, showed a class-related P30 of 23, 68, 100,
      and 138 W for the male athletes (n=38). Sprint power relative to body weight
      varied between 0.36 W X kg BW(-1)+/-0.04 and 1.85 W X kg BW(-1)+/-0.43 for the
      different subject groups. Propulsion technique in terms of forces applied to the
      rim and timing showed significant differences between subject groups for the
      majority of parameters studied. Apart from the mediolateral force and the
      negative dip at the start of the push phase, the technique parameters were
      significantly related to power production. Fraction effective force, the ratio
      between the total force vector and the effective force applied to the hand rim,
      appeared low on average (especially for subjects with cerebral palsy and those
      with a high spinal lesion) but showed a significant correlation with power output
      (r=0.5). In general, propulsion technique parameters were related to both
      performance and functionality. The number of training hours showed a small but
      significant relation with peak power (r=0.31), peak torque (r=0.4), the amount of
      work per push (r=0.41) and the total force vector (r=0.31), stressing the role of
      training status, next to disability, as important mediating factor in both
      propulsion technique as well as performance capacity. No association between
      training hours and fraction effective force was seen. It can be concluded that
      propulsion technique and performance parameters are highly variable among
      wheelchair athletes. Also, propulsion technique is strongly associated with
      functionality and training hours and does clearly relate to performance. The
      current results on technique and performance and their possible causal
      relationship, but also with impairment and sports discipline, must be further
      substantiated in a longitudinal study design.

PMID- 9635558
TI  - Medical student referral patterns for musculoskeletal disorders.
AB  - The purpose of this study was to determine the relationship between medical
      student knowledge and exposure to physiatry and the student's referral patterns
      for musculoskeletal disorders. Surveys were mailed to senior medical students at
      five United States medical schools across the country with a response rate of 26%
      (n=191). Five common musculoskeletal and neurologic disorders were presented as
      clinical vignettes and the student was asked to assume the role of a primary care
      physician and refer the patient to one of eight specialists listed. A section to
      assess the student's subjective overall knowledge and exposure to these fields
      was also included. Physiatrists received 27% of the referrals for evaluation and
      treatment of chronic low-back pain, 3% of the referrals for acute low-back pain,
      10% of the referrals for carpal tunnel syndrome, 22% of the referrals for an
      industrial medicine injury, and 20% of the referrals for a sports medicine
      injury. The frequency of physiatry referrals for three of the five cases was
      significantly correlated (P < 0.05) with the student's overall knowledge of
      physical medicine and rehabilitation (PM&R). The presence of a department of PM&R
      at the student's school, however, did not have a significant impact on the rate
      of referrals. The results indicate that senior medical students referral patterns
      are strongly influenced by knowledge of PM&R. This suggests that focusing efforts
      on increasing this awareness may be an effective means of increasing referrals to
      physiatry in the future.

PMID- 9635559
TI  - Electromyographic localization of the palmaris brevis muscle.
AB  - The palmaris brevis (PB) is the only muscle frequently innervated by the
      superficial branch of the ulnar nerve. It is clinically involved in patients with
      sensory impairment of the ulnar nerve sparing the deep branch as seen in mild
      cases of cyclist or crutch palsy. It is also involved in palmaris brevis spasm
      syndrome. A technique is described that makes it possible to localize the PB
      distinctly from its neighbors by electromyographic (EMG) pin examination. Methods
      include prospective (1) anatomic measurement in 10 cadavers and (2) EMG pin
      examination in 12 normal subjects measuring rise time (ms) and RMS voltage output
      (microV). Results showed (1) the area of the PB in elderly cadavers was 2.1+/-0.7
      x 2.1+/-0.3 cm with a thickness of 0.2+/-.01 cm and (2) in the live subjects, the
      muscle could be located with identification of motor unit potentials having a
      rise time <1 ms 100% of the time. In conclusion, the PB can be localized for EMG
      analysis by using an approach parallel to surface of the palm. Clinically, it
      could be a useful complement to diagnose neuropathy involving the superficial
      fibers of the ulnar nerve.

PMID- 9635560
TI  - Examination of deficits in conceptual reasoning abilities associated with spina
      bifida.
AB  - This study explores the "higher order" cognitive abilities of conceptual
      reasoning, problem solving, mental flexibility, and efficiency in 36 adolescents
      with spina bifida. The subjects, age 10 to 23 years, were assessed on a set of
      neuropsychological measures, and an individual profile analysis was conducted.
      All subjects, regardless of intelligence quotient, evidenced significant
      impairments of mental flexibility, efficiency of processing, conceptualization,
      or problem-solving ability. Separate data analysis was carried out for subjects
      with an average intelligence quotient. Results indicated a high degree of
      variability within profiles with at least one area of dysfunction (as determined
      by performance less than the 15th percentile) for each subject. This study
      demonstrates the need for individual analysis of "higher order" cognitive
      functions including conceptual reasoning, problem solving, mental flexibility,
      and efficiency of thinking for children who have spina bifida, regardless of
      level of lesion or general intelligence level. It is argued that
      neuropsychological deficits underlie the "motivational" and academic difficulties
      observed often among this population, especially for those with an average
      intelligence quotient. These data support the need to assess conceptual abilities
      in children with spina bifida and to provide consultation and early intervention
      services.

PMID- 9635561
TI  - Measuring frailty in the hospitalized elderly: concept of functional homeostasis.
AB  - Functional homeostasis is the ability of an individual to withstand illness
      without loss of function. We investigate whether the level of functional
      homeostasis predicts adverse outcomes in the 6 months posthospital discharge in
      older men and women. A prospective cohort study was conducted in an acute care
      geriatric inpatient unit of a university hospital. Subjects included a
      consecutive series of patients admitted to the unit. The Functional Independence
      Measure (FIM) instrument was used to assess patients at four time points:
      preillness, hospital admission, hospital discharge, and 6 months postdischarge.
      Of the 122 subjects available for analysis, 64 (52%) experienced a decline in
      functional level from preillness to hospital discharge and were defined as having
      poor functional homeostasis, whereas 58 (48%) experienced no change or an
      increase in functional status and were defined as having good functional
      homeostasis. Those with poor functional homeostasis had a higher 6-month
      readmission rate to the hospital (59.4 v 39.7%; P=0.03) and a higher rate of any
      adverse outcome (78.1 v 50%; P=0.001) than those with good functional
      homeostasis. In logistic regressive analyses, functional homeostasis remained a
      significant and powerful predictor of adverse outcomes independent of actual
      level of function at discharge, age, gender, living status, and other factors
      that might influence outcomes. Change in functional status associated with an
      acute illness is an independent predictor of adverse outcomes and, in this study,
      a better predictor than actual level of function at discharge. Functional
      homeostasis is one approach to the quantification of the important but elusive
      concept of frailty in the elderly.

PMID- 9635562
TI  - Diagnosis of a C-2 fracture during physiatric consultation: a case report.
AB  - Consultation in the acute care setting allows physiatrists to make significant
      contributions. In our case, a 90-year-old woman presented to the emergency room
      after falling down five stairs. Six view C-spine films taken at that time
      revealed no fracture. She was sent home on anti-inflammatory medication and was
      later admitted for gastritis. A repeat six-view C-spine series again revealed no
      fracture. Physiatry was then consulted to prescribe modalities and therapies for
      "cervical strain." On examination, the patient demonstrated severely decreased
      neck range of motion limited by pain, with pain radiating down her right arm.
      Physiatry recommended obtaining a C-spine magnetic resonance image to rule out
      occult fracture or herniated disc before proceeding with therapies. The magnetic
      resonance image revealed a complex C-2 fracture consisting of a Type III odontoid
      component. Computed tomographic scan was then performed to obtain a high
      resolution assessment of the bony architecture. The computed tomographic scan
      revealed a high degree of comminution, including bilateral pedicle fractures and
      a fracture through the left transverse foramen of C-2. The patient was placed in
      a hard cervical collar and seen by a neurosurgeon. Had therapies been initiated
      before physiatric consultation, the patient could have experienced significant
      neurologic complications, including the possibility of becoming tetraplegic. This
      case demonstrates that physiatrists play a crucial role in the evaluation of
      acute care patients before the initiation of therapies. The authors will review
      pertinent history and the results of physical and diagnostic tests.

PMID- 9635563
TI  - Cost-effectiveness of venous thrombosis prophylaxis after ischemic stroke.

PMID- 9635565
TI  - Fibrillation potentials and positive sharp waves.

PMID- 9635564
TI  - Are transition year programs obsolete because of proposed changes in graduate
      medical education funding?

PMID- 9635566
TI  - Biological properties of recombinant alpha-interferons: 40th anniversary of the
      discovery of interferons.
AB  - IFNs were first described as potent antiviral agents 40 years ago, and
      recombinant IFN-alpha2a and IFN-alpha2b were approved for the treatment of hairy
      cell leukemia just 11 years ago. Today, alpha-IFNs are approved worldwide for the
      treatment of a variety of malignancies and virologic diseases. Although the exact
      mechanism of action of IFN-alpha in the treatment of such diseases is not fully
      understood, many advances have been made in the characterization of the
      physicochemical and diverse biological properties of this highly pleiotropic
      cytokine. Here we review recent developments in our understanding of the
      antiviral and immunoregulatory properties of IFN-alpha, the nature of the
      multisubunit IFN-alpha receptor, and the molecular mechanisms of signal
      transduction. Where available, we have included comparative data on recombinant
      alpha-IFNs derived from both naturally occurring and nonnaturally occurring
      synthetic genes. We also review clinical data and data on the side effects and
      antigenicity of different sources of recombinant alpha-IFNs in humans. These
      latter topics are of clinical interest, because they may potentially affect the
      efficacy of these various products. Hopefully, what is already known about IFN
      will prompt further exploration into the mechanism(s) of action of IFN-alpha and
      thus deliver new applications for this prototypic cytokine, whose full
      therapeutic potential is yet to be realized.

PMID- 9635567
TI  - Mutation of the PTEN tumor suppressor gene in endometrial hyperplasias.
AB  - Mutation and deletion of the PTEN tumor suppressor gene occurs in about 40% of
      endometrial carcinomas. The purpose of this study was to determine whether PTEN
      mutations also are present in endometrial hyperplasias, which are premalignant
      precursors of invasive endometrial adenocarcinomas. Genomic DNA from 51
      endometrial hyperplasias was extracted from paraffin blocks, and PCR was used to
      amplify the nine exons of the PTEN gene. These products were screened using
      single-strand conformation analysis, and variant bands were sequenced. Somatic
      mutations in the PTEN gene were seen in 10 of 51 cases (20%), and two mutations
      were found in one case. An identical 4-bp deletion in exon 8 was seen in three
      cases, and 8 of 11 PTEN mutations predicted truncated protein products. There was
      no higher frequency of PTEN mutations in endometrial hyperplasias with atypia (6
      of 32; 19%) relative to those without atypia (4 of 19; 21%). These data suggest
      that inactivation of the PTEN tumor suppressor gene is an early event in the
      development of some endometrial cancers.

PMID- 9635568
TI  - Apoptosis and perturbation of cell cycle progression in an acidic environment
      after hyperthermia.
AB  - The effects of an acidic environment on the induction of apoptosis by 42 degrees
      C hyperthermia were investigated. An acidic environment (pH 6.6) enhanced the
      hyperthermia-induced apoptosis in HL-60 human promyelocytic leukemia cells as
      judged by the DNA fragmentation, flow cytometric analysis of DNA content, and
      cleavage of poly(ADP-ribose) polymerase. Hyperthermia exerted no effect on the
      expression of Bcl-2 and Bax, regardless of the environmental acidity during
      heating. The time of increase in apoptosis after heating coincided with the time
      of decrease in the G1-phase cell population. It seemed that the increase in heat
      induced apoptosis in HL-60 cells in an acidic environment was due to a direct
      increase in the proteolytic cleavage of poly(ADP-ribose) polymerase by acidic
      caspases without the involvement of Bcl-2 and Bax, and that heat-induced
      apoptosis occurred during G1 phase in HL-60 cells.

PMID- 9635569
TI  - Genetic vaccination against the melanocyte lineage-specific antigen gp100 induces
      cytotoxic T lymphocyte-mediated tumor protection.
AB  - Melanocyte lineage-specific antigens, such as gp100, have been shown to induce
      both cellular and humoral immune responses against melanoma. Therefore, these
      antigens are potential targets for specific antimelanoma immunotherapy. A novel
      approach to induce both cellular and humoral immunity is genetic vaccination, the
      injection of antigen-encoding naked plasmid DNA. In a mouse model, we
      investigated whether genetic vaccination against the human gp100 antigen results
      in specific antitumor immunity. The results demonstrate that vaccinated mice were
      protected against a lethal challenge with syngeneic B16 melanoma-expressing human
      gp100, but not control-transfected B16. Both cytotoxic T cells and IgG specific
      for human gp100 could be detected in human gp100-vaccinated mice. However, only
      adoptive transfer of spleen-derived lymphocytes, not of the serum, isolated from
      protected mice was able to transfer antitumor immunity to nonvaccinated
      recipients, indicating that CTLs are the predominant effector cells. CTI, lines
      generated from human gp100-vaccinated mice specifically recognized human gp100.
      Interestingly, one of the CTL lines cross-reacted between human and mouse gp100,
      indicating the recognition of a conserved epitope. However, these CTLs did not
      appear to be involved in the observed tumor protection. Collectively, our results
      indicate that genetic vaccination can result in a potent antitumor response in
      vivo and constitutes a potential immunotherapeutic strategy to fight cancer.

PMID- 9635570
TI  - Mapping of ER gene CpG island methylation-specific polymerase chain reaction.
AB  - Southern analysis has shown that DNA from 25% of primary estrogen receptor (ER)
      alpha-negative breast tumors displays aberrant methylation at one site within the
      ER gene CpG island. To examine more sites and increase sensitivity, we developed
      a methylation-specific PCR assay to map methylation of the entire ER CpG island.
      The island was unmethylated in normal breast tissue and ER-positive breast cancer
      cell lines, but extensively methylated in all ER-negative cell lines and breast
      tumors examined. In addition, some of the ER-positive/progesterone receptor
      negative and ER-positive/progesterone receptor-positive tumors (about 70% and
      35%, respectively) displayed methylation of the ER CpG island, suggesting that
      this heterogeneity within tumor cell populations could potentially shed light on
      the etiology of ER-negative recurrent tumors arising from ER-positive tumors.

PMID- 9635571
TI  - Beta-catenin mutations in human prostate cancer.
AB  - Beta-catenin plays essential roles in both intercellular adhesion and signal
      transduction. As a signaling molecule, beta-catenin supplies an activating domain
      to the T-cell factor/lymphoid enhancer-binding factor family of DNA-binding
      proteins and activates gene transcription. Posttranslational stabilization of
      beta-catenin, leading to elevated protein levels and constitutive gene
      activation, has been proposed as an important step in oncogenesis. Stabilization
      of beta-catenin can occur through mutation to highly conserved amino acids
      encoded in exon 3 of the beta-catenin gene (CTNNB1). To determine whether this
      pathway of malignant transformation is important in prostate cancer, we analyzed
      104 prostate cancer tissue specimens, 4 prostate cancer cell lines, and 3
      prostate tumor xenografts for activating mutations in exon 3 of CTNNB1. Mutations
      were detected in 5 of the 104 prostate cancer tissue samples. Four of the five
      mutations involved serine or threonine residues implicated in the degradation of
      beta-catenin. A fifth tumor had a mutation at codon 32, changing a highly
      conserved aspartic acid to a tyrosine. Mutational analysis of multiple regions
      from several tumor samples showed that the beta-catenin mutations were present
      focally and therefore may occur during tumor progression.

PMID- 9635572
TI  - Activation of the beta-catenin gene in primary hepatocellular carcinomas by
      somatic alterations involving exon 3.
AB  - We screened 75 primary hepatocellular carcinomas for somatic mutations in the
      entire coding region of the beta-catenin gene. We detected somatic mutations in
      14 tumors; 12 were considered to cause amino acid substitutions and 2 were
      interstitial deletions of 51 or 195 nucleotides of genomic DNA, corresponding to
      exon 3. Among the 12 point mutations, 6 occurred at potential serine/threonine
      phosphorylation residues of codons 33, 41, or 45. The remaining six tumors
      contained a mutation at codon 32 (aspartic acid) or 34 (glycine), flanking to the
      serine residue at codon 33. By Western blot analysis, we confirmed accumulation
      of beta-catenin in five tumors for which frozen tissues were available; the five
      included tumors in which amino acid alterations had occurred at codons 32, 34, or
      45, and one with a 17-amino acid deletion. Our results suggested that
      accumulation of beta-catenin due to amino acid substitutions at potential
      serine/threonine phosphorylation residues or at their neighboring codons or
      interstitial deletions involving exon 3 could contribute to hepatocellular
      carcinogenesis.

PMID- 9635573
TI  - Cell motility of tumor cells visualized in living intact primary tumors using
      green fluorescent protein.
AB  - Metastasis is the leading cause of death in cancer patients. Cell motility is
      believed to be a necessary step in the metastatic process (L. Liotta and W. G.
      Stetler-Stevenson, In: Cancer: Principles and Practice of Oncology, pp. 134-149,
      1993). Currently, most methods available to study the behavior of metastatic
      tumor cells are indirect, e.g., cell motility is examined in vitro and the
      results are correlated with metastatic capability (A. W. Partin, et al., Cancer
      Treat. Res., 59: 121-130, 1992). We have developed a model that directly examines
      the motility of metastatic primary tumor cells in situ. A metastatic rat breast
      cancer cell line was established that constitutively expresses green fluorescent
      protein. Upon s.c. injection of these cells into the mammary fat pad of female
      Fischer 344 rats, primary and metastatic tumors form that fluoresce when they are
      excited with FITC-filtered light. Animations of metastatic tumor cells moving in
      live rats were generated by intravital imaging of the primary tumor in situ on a
      laser scanning confocal microscope. With this model, the behavioral phenotype of
      metastatic and nonmetastatic tumor cells can be described and determined. This
      information will allow the effects of genetic manipulations or therapeutic
      treatments on this phenotype to be determined (D. R. Soll, Int. Rev. Cytol., 163:
      43-104, 1995). This is the first time that living primary tumor cells in a live
      animal have been visualized as part of a clinically relevant model.

PMID- 9635575
TI  - Enzymatic activation of a doxorubicin-peptide prodrug by prostate-specific
      antigen.
AB  - New approaches to target cytotoxic therapy specifically to metastatic prostate
      cancer sites are urgently needed. As such an approach, an inactive prodrug was
      synthesized by coupling the primary amine of doxorubicin to the COOH-terminal
      carboxyl of a seven-amino acid peptide carrier (i.e., Mu-His-Ser-Ser-Lys-Leu-Gln
      Leu). The seven-amino acid peptide was documented to be hydrolyzable specifically
      by the serine protease prostate-specific antigen (PSA) to liberate the active
      cytotoxin L-leucyl-doxorubicin. Primary cultures of PC-82 human prostate cancer
      cells secreted high levels of enzymatically active PSA (i.e., 70 +/- 5 ng of
      enzymatically active PSA/10(6) cells/24 h), whereas LNCaP human prostate cancer
      cells produced lower levels of enzymatically active PSA (i.e., 2.3 +/- 1 ng/10(6)
      cells/24 h). LNCaP cells, however, secreted sufficient amounts of enzymatically
      active PSA to activate the doxorubicin prodrug to a cytotoxic form in vitro. The
      specificity of the cytotoxic response to the prodrug was demonstrated by the fact
      that 70 nM of the prodrug killed 50% of the PSA-producing LNCaP cells, whereas
      doses as high as 1 microM had no cytotoxic effect on PSA-nonproducing TSU human
      prostate cancer cells in vitro.

PMID- 9635574
TI  - Allelic deletion analysis of the FHIT gene predicts poor survival in non-small
      cell lung cancer.
AB  - The fragile histidine triad (FHIT) gene at chromosome 3p14.2 is a candidate tumor
      suppressor gene linked to cancers of the lung, breast, colon, pancreas, and head
      and neck. Reports of frequent allelic deletion and abnormal transcripts in
      primary lung tumors plus recent evidence that it is targeted by tobacco smoke
      carcinogens suggest that it plays an important role in lung carcinogenesis. Non
      small cell lung carcinoma still maintains a poor 5-year survival rate with the
      stage of disease at presentation as a major determinant of prognosis. We examined
      for allelic deletion at the FHIT locus in a series of 106 non-small cell lung
      carcinomas for which a full clinical, epidemiological, and 5-year survival
      profile was available. We found an allelic deletion frequency of 38% at one or
      two intragenic microsatellites. Allelic deletion of FHIT was related to tumor
      histology with 4 of 20 adenocarcinomas (20%) displaying loss of heterozygosity
      (LOH) compared with 12 of 22 (55%) nonadenocarcinomas (P = 0.03). We found that
      63% of tumors with LOH of FHIT also had p53 missense mutations whereas only 26%
      with LOH had wild type p53 negative sequence (P = 0.02). We also found a
      significant trend toward poorer survival in patients with LOH of at least one
      locus of the FHIT gene (log rank, P = 0.01). This survival correlation is
      independent of tumor stage, size, histological subtype, degree of
      differentiation, and p53 mutation status. Our data support the hypothesis that
      the loss of the FHIT contributes to the molecular pathogenesis of human lung
      cancer and is an indicator of poor prognosis.

PMID- 9635576
TI  - Enhanced binding of antibodies to the DTR motif of MUC1 tandem repeat peptide is
      mediated by site-specific glycosylation.
AB  - The epithelial mucin MUC1 is an important tumor marker of breast cancer and other
      carcinomas. Its immunodominant DTR motif, which is the principal target for
      immunotherapeutic approaches, has been assumed until recently not to be
      glycosylated in both normal and tumor MUC1 and to acquire its immunogenic
      conformation by virtue of a certain number of tandem repeats. We present evidence
      that the antigenicity of the single repeat toward a considerable number of
      antibodies to the DTR motif is greatly enhanced if it is glycosylated within this
      motif, and only in this position. Twenty-eight monoclonal anti-MUC1 antibodies
      with DTR specificity were tested for binding to synthetic 21-mer (AHG21) or 20
      mer (HGV20) tandem repeat peptides O-glycosylated with galactose beta1-3N
      acetylgalactosamine alpha or N-acetylgalactosamine alpha at defined Thr or Ser
      positions. Binding was measured in ELISA experiments using the glycopeptides as
      plate-immobilized antigens or as inhibitors in solution. At least 12 antibodies
      revealed significantly enhanced binding to the peptides glycosylated at the DTR
      motif (Thr-10) as compared to positional isomers glycosylated at Thr-5, Ser-6,
      Ser-16, or Thr-17 and to the nonglycosylated peptides. Six antibodies (VU-3-C6,
      A76-A/C7, Ma552, VU-11-D1, VU-12-E1, and VU-11-E2) that were unreactive with the
      monomeric repeat peptide did bind to the DTR-glycosylated peptide. Several lines
      of evidence suggest that glycosylation with N-acetylgalactosamine is sufficient
      for the observed enhancement effect. Our results are of special interest in
      conjunction with the recent observation that the DTR motif of lactation
      associated MUC1 is O-glycosylated in vivo (Muller et al., J. Biol. Chem., 272:
      24780-24793, 1997). They may have consequences for the design of efficient tumor
      vaccines.

PMID- 9635577
TI  - Citrus auraptene exerts dose-dependent chemopreventive activity in rat large
      bowel tumorigenesis: the inhibition correlates with suppression of cell
      proliferation and lipid peroxidation and with induction of phase II drug
      metabolizing enzymes.
AB  - In our previous short-term experiment, Citrus auraptene inhibited the development
      of azoxymethane (AOM)-induced aberrant crypt foci, which are precursor lesions
      for colorectal carcinoma. In the present study, the possible inhibitory effect of
      dietary administration of auraptene was investigated using an animal colon
      carcinogenesis model with a colon carcinogen AOM. Male F344 rats were given s.c.
      injections of AOM (15 mg/kg body weight) once a week for 3 weeks to induce colon
      neoplasms. They also received diets containing 100 or 500 ppm auraptene for 4
      weeks in groups of "initiation" feeding, starting 1 week before the first dosing
      of AOM. The diets containing auraptene were also given to rats for 38 weeks in
      groups of "postinitiation" feeding. At the termination of the study (38 weeks),
      dietary administration of auraptene caused dose-dependent inhibition in AOM
      induced large bowel carcinogenesis. Auraptene feeding during the initiation phase
      reduced the incidence of colon adenocarcinoma by 49% at 100 ppm (P = 0.099) and
      65% at 500 ppm (P = 0.0075). Auraptene administration during the postinitiation
      phase inhibited the incidence of colon adenocarcinoma by 58% at 100 ppm (P =
      0.021) and 65% at 500 ppm (P = 0.0075). Also, the multiplicity of colon carcinoma
      was significantly reduced by initiation feeding at a dose level of 500 ppm (P <
      0.01) and postinitiation feeding at a level of 100 and 500 ppm (P < 0.05 and P <
      0.01, respectively). Feeding of auraptene suppressed the expression of cell
      proliferation biomarkers (ornithine decarboxylase activity and polyamine content)
      in the colonic mucosa and reduced the production of aldehydic lipid peroxidation
      [malondialdehyde and 4-hydroxy-2(E)-nonenal]. In addition, auraptene increased
      the activities of Phase II drug-metabolizing enzymes (glutathione S-transferase
      and quinone reductase) in the liver and colon. These findings suggest that the
      inhibitory effects of auraptene on AOM-induced colon tumorigenesis at the
      initiation level might be associated, in part, with increased activity of Phase
      II enzymes, and those at the postinitiation stage might be related to suppression
      of cell proliferation and lipid peroxidation in the colonic mucosa.

PMID- 9635578
TI  - Tumorigenicity of sodium ascorbate in male rats.
AB  - Sodium ascorbate, like other sodium salts such as saccharin, glutamate, and
      bicarbonate, produces urinary alterations when fed at high doses to rats, which
      results in mild superficial urothelial cytotoxicity and regeneration but not
      tumors in a standard 2-year bioassay. Sodium saccharin was shown to produce a low
      incidence of bladder tumors in rats if administered in a two-generation bioassay.
      In the present study, we evaluated sodium ascorbate in a two-generation bioassay
      that involved feeding to the male and female parental F344 rats for 4 weeks
      before mating, feeding the dams during gestation and lactation, and then feeding
      the weaned (at 28 days of age) male F1 generation rats for the remainder of their
      lifetime (up to 128 weeks of the experiment). Dietary levels of 1.0, 5.0, and
      7.0% sodium ascorbate were tested. At 5.0 and 7.0% sodium ascorbate, there was an
      increase in urinary bladder urothelial papillary and nodular hyperplasia and the
      induction of a few papillomas and carcinomas. There was a dose-responsive
      increase in renal pelvic calcification and hyperplasia and inhibition of the
      aging nephropathy of rats even at the level of 1% sodium ascorbate. Because the
      short-term urothelial effects of sodium ascorbate in rats are inhibited by
      treatments producing urinary acidification to pH < 6.0, we coadministered high
      doses of long-term NH4Cl to groups of rats with 5.0 or 7.0% sodium ascorbate to
      evaluate the long-term effects. The combination of 7.0% sodium ascorbate plus
      2.78% NH4Cl in the diet was toxic, and the group was terminated early during the
      course of the experiment. The group fed 5.0% sodium ascorbate plus 2.04% NH4Cl
      showed complete inhibition of the urothelial effects of sodium ascorbate and
      significant inhibition of its renal effects. We also demonstrated the presence of
      a calcium phosphate-containing urinary precipitate in rats fed sodium ascorbate
      at all doses, in a dose-responsive manner. The formation of the precipitate was
      inhibited by coadministration with NH4Cl. The proliferative effects of sodium
      ascorbate on the male rat urinary tract in this study are similar to those seen
      with sodium saccharin when administered in a two-generation bioassay. Mechanistic
      information suggests that this is a high-dose, rat-specific phenomenon.

PMID- 9635579
TI  - Potent inhibition of hemangioma formation in rats by the acyclic nucleoside
      phosphonate analogue cidofovir.
AB  - The acyclic nucleoside phosphonate analogue cidofovir elicited a marked
      protection against hemangioma growth in newborn rats that had been infected i.p.
      with a high titer of murine polyomavirus. Untreated, infected rats developed
      cutaneous, i.m., and cerebral hemangiomas associated with severe hemorrhage and
      anemia leading to death within 3 weeks postinfection (p.i.). s.c. treatment with
      cidofovir at 25 mg/kg, once a week, resulted in a complete suppression of
      hemangioma development and associated mortality when treatment was initiated at 3
      days p.i. (100% survival compared with 0% for the untreated animals). Cidofovir
      still afforded 40% survival and a significant delay in tumor-associated mortality
      when treatment was started at a time at which cerebral hemangiomas were already
      macroscopically visible (i.e., 9 days p.i.). Infectious virus or viral DNA was
      undetectable in the brain at different times p.i. as assessed by means of (a) a
      DNA-DNA hybridization assay and (b) titration of the brain for infectious virus
      content, indicating that there was no viral replication in murine polyomavirus
      infected rats. Moreover, a semiquantitative PCR for viral protein 1 DNA revealed
      that the amount of viral protein 1 DNA declined with time after infection to
      become virtually undetectable at 18 days p.i. Therefore, an antitumor or
      antiangiogenic effect, rather than inhibition of viral replication, may be the
      reason for the inhibitory activity of cidofovir in this model. Cidofovir may thus
      be further explored for the treatment of vascular tumors and, in particular, life
      threatening juvenile hemangiomas.

PMID- 9635580
TI  - Tumor efficacy and bone marrow-sparing properties of TER286, a cytotoxin
      activated by glutathione S-transferase.
AB  - TER286 is a latent drug activated by human glutathione S-transferase (GST)
      isoforms P1-1 and A1-1 to produce a nitrogen mustard alkylating agent. M7609
      human colon carcinoma, selected for resistance to doxorubicin, and MCF-7 human
      breast carcinoma, selected for resistance to cyclophosphamide, both showed
      increased sensitivity to TER286 over their parental lines in parallel with
      increased expression of GST P1-1. In primary human tumor clonogenic assays, the
      spectrum of cytotoxic activity observed for TER286 was both broad and unusual
      when compared to a variety of current drugs. In murine xenografts of M7609
      engineered to have high, medium, or low GST P1-1, responses to TER286 were
      positively correlated with the level of P1-1. Cytotoxicity was also observed in
      several other cell culture and xenograft models. In xenografts of the MX-1 human
      breast carcinoma, tumor growth inhibition or regression was observed in nearly
      all of the animals treated with an aggressive regimen of five daily doses. This
      schedule resulted in a 24-h posttreatment decline in bone marrow progenitors to
      60% of control and was no worse than for a single dose of TER286. These studies
      have motivated election of TER286 as a clinical candidate.

PMID- 9635581
TI  - Purification and characterization of a Mg2+-dependent endonuclease (AN34) from
      etoposide-treated human leukemia HL-60 cells undergoing apoptosis.
AB  - An important biochemical hallmark of apoptosis is the cleavage of chromatin into
      oligonucleosomal fragments. Here, we purified a Mg2+-dependent endonuclease from
      etoposide-treated HL-60 cells undergoing apoptosis. High levels of Mg2+-dependent
      endonuclease activity were detected in etoposide-treated HL-60 cells, and this
      activity increased in a time-dependent manner following etoposide treatment. Such
      an activity could not be detected in untreated cells or in cells treated with
      etoposide in the presence of the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp
      (OMe)-fluoromethyl ketone (zVAD-fmk) or the serine protease inhibitor tosyl-L
      phenylalanine chloromethyl ketone (TPCK). This Mg2+-dependent endonuclease was
      purified by a series of chromatographic procedures. The enzyme preparation showed
      a single major protein band with Mr 34,000, determined by SDS-PAGE. The presence
      of the Mr 34,000 Mg2+-dependent endonuclease was also confirmed by activity gel
      analysis. The enzyme required only Mg2+ for full activity. pH optimum was in the
      range of 6.5-7.5. This enzyme introduced single- and double-strand breaks into
      SV40 DNA and produced internucleosomal DNA cleavage in isolated nuclei from
      untreated cells. The DNA breaks were terminated with 3'-OH, consistent with
      characteristic products of apoptotic chromatin fragmentation. We propose to
      designate this Mr 34,000 Mg2+-dependent endonuclease AN34 (apoptotic nuclease Mr
      34,000).

PMID- 9635582
TI  - Anticancer efficacy in vivo and in vitro, synergy with 5-fluorouracil, and safety
      of recombinant methioninase.
AB  - The elevated exogenous-methionine dependency of tumors for growth has been
      observed in all major cancer cell types. We have previously cloned a methioninase
      (rMETase) from Pseudomonas putida to deplete methionine. Growth inhibition
      followed by apoptotic cell death was induced by treatment of tumor cells with
      rMETase in vitro. A single i.p. injection of 300 units of rMETase can lower the
      serum methionine level in the mice from 70 microM to less than 1 microM within 2
      h and maintain this depleted level for 8 h. Repeated dosing of rMETase of tumor
      bearing mice could be administered without acute immune-hypersensitivity. rMETase
      treatment demonstrated growth inhibitory activity against human tumors in nude
      mice, including those which were multiple drug-resistant. No body weight loss or
      hematotoxicity, except a slight anemia, was found throughout the therapy. The
      combined treatment of the Lewis lung carcinoma with a fixed rMETase dose and
      increasing doses of 5-fluorouracil (5-FU) resulted in a dose-dependent enhanced
      antitumor efficacy for survival as well as tumor growth inhibition. Thus,
      methionine depletion by rMETase potentiates the antitumor efficacy of 5-FU. The
      data presented in this report thus indicate that rMETase is active alone, is
      synergistic in combination with 5-FU, and has negligible toxicity suggesting a
      novel clinical approach for effective cancer therapy.

PMID- 9635583
TI  - Preferential cytotoxicity of cells transduced with cytosine deaminase compared to
      bystander cells after treatment with 5-flucytosine.
AB  - In vitro experiments from our laboratory and others have suggested that herpes
      simplex virus thymidine kinase (HSV-TK)/ganciclovir (GCV) gene therapy depends on
      gap junctional intercellular communication (GJIC) to produce a strong bystander
      effect. Furthermore, we have shown that cells transduced with HSV-TK can be
      protected from GCV-mediated toxicity by GJIC with bystander cells. We wished to
      determine whether GJIC affected either the bystander or protective effect of the
      cytosine deaminase (CD)/5-flucytosine (5-FC) gene therapy approach, in which CD
      converts 5-FC to 5-fluorouracil (5-FU). To test this, we designed a coculture
      system using communication-competent WB rat hepatocytes and a noncommunicating
      subclone (aB1), which were transduced with CD and with antibiotic resistance
      genes so that we could independently determine the survival of the CD-containing
      or bystander cells. We found that, compared to the HSV-TK/GCV strategy, bystander
      killing resulting from treatment with CD/5-FC does not depend on GJIC. However,
      our most striking finding was that both communication-competent and -incompetent
      CD-transduced cells were preferentially killed, by a factor of up to 500,
      compared to bystander cells. The lesser dependence of the CD/5-FC system on GJIC,
      combined with the finding that most cancer cells lack the capacity for GJIC,
      suggest that the CD/5-FC system may be superior to the HSV-TK/GCV approach for
      gene therapy. However, the premature death of the CD-transduced 5-FU "factory"
      suggests that other strategies may be necessary to produce a sufficient quantity
      of 5-FU for a duration long enough to produce permanent tumor regression.

PMID- 9635584
TI  - Differential inhibition of fluid accumulation and tumor growth in two mouse
      ascites tumors by an antivascular endothelial growth factor/permeability factor
      neutralizing antibody.
AB  - In the accompanying paper (Luo et al., Cancer Res., 58: 2652-2660, 1998), we
      demonstrated that vascular endothelial growth factor (VEGF), also designated
      vascular permeability factor (VPF), significantly accumulated in all mouse
      malignant ascites tested, suggesting its fundamental role in ascites tumors.
      Removal of VEGF may inhibit the development of ascites tumors. In this study,
      using a goat antimouse VEGF-neutralizing antibody, we tested this hypothesis with
      two well-defined syngeneic mouse ascites tumors: MM2 breast adenocarcinoma and
      OG/Gardner lymphoma 6C3HED (expressing moderate and low levels of VEGF,
      respectively). This antibody significantly inhibited MM2 and OG cell-free ascites
      fluid-induced hyperpermeability of mouse peritoneal microvessels and in vitro
      endothelial cell growth. Mice bearing tumors were administered i.p. daily with
      the antibody or normal goat IgG as controls for 8 days, at doses of 20-fold (for
      MM2-bearing mice) or 40-fold (for OG-bearing mice) the estimated amounts of VEGF
      that kinetically accumulated in the ascites fluid after the tumor inoculation.
      The average volume of ascites fluid, number of tumor cells and leaked RBCs, and
      the peritoneal microvessel permeability in MM2-bearing mice that received the
      antibody treatment were significantly lower than those in the matched controls (P
      < 0.01). Unexpectedly, OG-bearing mice did not show satisfactory response to the
      anti-VEGF treatment. This discrepancy was not likely due to inadequate doses or
      different host immune responses, but it was quite possibly to the different
      characteristics of MM2 carcinoma and OG lymphoma tumors, the latter being
      strongly invasive, and/or the existence of an inflammatory mediator(s), such as
      bradykinin or cytokine(s) other than VEGF. In summary, our results directly
      demonstrated, for the first time, differential roles for VEGF in ascites tumors
      in vivo and suggest the potential of VEGF inhibition as a specific therapy for
      ascites tumors of carcinoma origin, which are the major cause of the malignant
      ascites in adult humans.

PMID- 9635585
TI  - Targeting p53 for adoptive T-cell immunotherapy.
AB  - p53 gene mutations occur in most human cancers and result in an altered protein
      product that accumulates within the cell. Although the observed endogenous human
      CTL response to p53 is weak, high-affinity, human p53-specific CTLs have been
      generated from HLA A2.1 transgenic mice immunized with human CTL epitope
      peptides. In this study, we examine the ability of HLA A2.1-restricted and human
      p53-specific CTLs from HLA A2.1 transgenic mice to suppress the growth of p53
      overexpressing human tumors in severe combined immunodeficient (SCID) mice. In
      vitro, murine p53(149-157)-specific CTLs selectively lysed the p53-overexpressing
      pancreatic carcinoma cell line Panc-1 but did not recognize HLA A2.1- tumor cells
      or HLA A2.1+ normal human fibroblasts. Furthermore, in vivo, the growth of
      established human tumor xenografts in SCID mice was significantly reduced and
      survival was prolonged after the administration of p53-specific CTLs but not
      after the administration of control CTLs or PBS alone. Following treatment with
      p53(149-157)-specific CTLs, regressing Panc-1 tumors were infiltrated by the CD8+
      CTLs, as demonstrated by immunohistochemistry. These findings suggest that
      p53(149-157)-specific and HLA A2.1-restricted murine CTLs suppress the growth of
      established Panc-1 tumors following adoptive transfer into SCID hosts and prolong
      their survival.

PMID- 9635586
TI  - Epitope mapping of a series of human thymidylate synthase monoclonal antibodies.
AB  - We have reported previously the development and application of several monoclonal
      antibodies to thymidylate synthase (TS). In this study, we used a series of
      overlapping 17-mer peptides that spanned the entire TS protein to map the epitope
      recognized by three TS monoclonal antibodies (TS 106, TS 109, and TS 110). Using
      an ELISA, we identified two peptides (R126-F142 and L131-R147) that bound all
      three antibodies, which suggests that each antibody recognized a similar epitope
      on TS. A second set of peptides, representing sequential single-residue
      truncations from either the amino terminus or the carboxyl terminus starting with
      a G129-E145 17-mer, was synthesized. A 10-amino acid sequence P133-F142
      (PVYGFQWRHF) was identified as the binding epitope for all three antibodies.
      Further investigation via substitution mutational analysis of each residue within
      this epitope revealed that residues F137, W139, R140, H141, and F142 were
      critical for maximal binding of TS 106 and TS 110. TS 109 showed a similar
      pattern except in regard to R140, with which there was no apparent loss of
      binding. In addition to the utility of the three antibodies in detecting and
      measuring TS levels, identification of the binding locus permits the potential
      application of these antibodies in the investigation of TS enzymatic and
      regulatory function.

PMID- 9635587
TI  - Aminosyn II effectively blocks renal uptake of 18F-labeled anti-tac disulfide
      stabilized Fv.
AB  - Because intact IgG has limitations as a tumor-imaging agent, radiolabeled Fv
      fragments are being evaluated. Due to the high renal accumulation of Fv
      fragments, methods to block renal uptake are being sought. This study evaluated
      how well Aminosyn II, a Food and Drug Administration-approved 15% amino acid
      solution, would block the renal accumulation of 18F anti-Tac disulfide-stabilized
      Fv (dsFv) fragments (small fragments with high renal uptake). The anti-Tac dsFv
      is directed against the alpha subunit of the interleukin 2 receptor. It was
      labeled at specific activities of 1.1-2.7 mCi/mg using N-succinimidyl 4
      [18F]fluoromethyl benzoate. Four adult baboons were injected i.v. with 0.7-1.9
      mCi and 150 microg of dsFv. Each baboon was preinjected with Aminosyn II i.v.
      and, on a separate occasion, with a control solution. Thirty min before injection
      of 18F-labeled anti-Tac dsFv, a bolus of either solution was given, followed by a
      constant infusion of 13.3 ml/kg/h. Quantitative positron emission tomography
      imaging was performed. The amino acid levels in serum were measured serially. The
      baseline levels of lysine (and other amino acids) in plasma were not
      significantly different in either the Aminosyn II or control infusion group and
      did not change during the control infusion. In the Aminosyn II group, lysine
      levels in plasma 5 min before anti-Tac dsFv infusion were 5-15 times higher than
      the baseline value and continued to rise during the infusion. The areas under the
      curve in blood of the 18F-labeled anti-Tac dsFv, from time of injection to end of
      imaging, expressed as percentage injected dose (%ID), were 28.94 +/- 4.05%ID x
      h/liter (mean +/- SD) for the control group and 32.09 +/- 11.15%ID x h/liter for
      the Aminosyn II group (P = 0.54). The peak concentration of 18F-labeled anti-Tac
      dsFv in the kidney of the controls was 24.53 +/- 4.34%ID; the value in the
      Aminosyn II group was 5.39 +/- 1.89%ID, representing a mean decrease of 78.5%.
      The times to reach 90% of the peak levels of 18F in the kidney were 5.6 +/- 3.0
      min for the Aminosyn II group and 33.8 +/- 4.8 min for the control group. The
      amounts excreted in urine by 90 min were 47.7 +/- 8.55%ID and 78.5 +/- 12.8%ID (P
      = 0.01) for the controls and Aminosyn II group, respectively. In conclusion,
      Aminosyn II effectively blocks the renal accumulation of 18F-labeled anti-Tac
      dsFv. Use of Aminosyn II should allow much higher tracer administration for the
      same radiation exposure to the target organ (kidney).

PMID- 9635588
TI  - Frequent loss of heterozygosity on the long arm of chromosome 6: identification
      of two distinct regions of deletion in childhood acute lymphoblastic leukemia.
AB  - Cytogenetic analysis of childhood acute lymphoblastic leukemia (ALL) identified
      nonrandom chromosomal abnormalities of the long arm of chromosome 6. Most of the
      alterations are deletions that are thought to be indicative of the presence of a
      tumor suppressor gene that is mutated on the remaining allele. These observations
      led us to consider whether 6q loss may contribute to the pathogenesis of
      childhood ALL. To define further a region containing this gene, we analyzed the
      loss of heterozygosity (LOH) of chromosome 6 in 113 primary ALL samples with
      matched normal DNA using 34 highly informative microsatellite markers. LOH was
      found in 17 (15%) samples at one or more of the loci, and partial or interstitial
      deletions of 6q were detected in 11 of these tumors. On the basis of these
      results, we performed a detailed deletional map and identified two distinct
      regions of deletion. The first region is flanked by D6S283 and D6S302 loci at
      6q21-22. The second region is flanked by D6S275 and D6S283 loci at 6q21. Clinical
      analysis determined that LOH of 6q was demonstrated both in precursor-B cell ALLs
      (15 of 93; 16%) and in T cell ALLs (2 of 19; 11%). In addition, 19 patients have
      been studied at diagnosis and relapse; 18 showed the same 6q21-22 structural
      abnormality at relapse (normal, 16 patients; LOH, 2 patients) as their initial
      presentation, suggesting, albeit with a small patient sample size, that 6q21-22
      deletions may be an initial event in leukemogenesis and may occur less frequently
      during the progression of childhood ALL. These data suggest the presence of
      putative tumor suppressor genes on chromosome arm 6q that are important in the
      development of both T and precursor-B childhood ALLs. Our map provides important
      information toward cloning putative ALL tumor suppressor genes.

PMID- 9635589
TI  - Disruption of the cyclin D/cyclin-dependent kinase/INK4/retinoblastoma protein
      regulatory pathway in human neuroblastoma.
AB  - The p16INK4a (MTS1) and pl8INK4c gene products are normal, and highly expressed,
      in human neuroblastoma cell lines. The retinoblastoma protein (pRb) was,
      nonetheless, phosphorylated and functional in these cells. Such high levels of
      p16INK4a/p18INK4c should normally inhibit cyclin-dependent kinase (CDK) 4 and 6
      activities in cells containing functional pRb, delaying cell cycle progression
      and growth. These neuroblastoma cell lines express both CDK4 and CDK6 mRNA and
      protein, but only significant CDK6 protein kinase activity was detected in this
      study. In addition, CDK6 was not present in p16INK4a immune complexes in cells
      with significant kinase activity, although p16INK4a levels were high. Others have
      shown that a specific mutation in the NH2-terminal region of the CDK4 gene
      product can disrupt p16INK4a binding, thereby bypassing its inhibitory activity.
      To determine whether mutation of the CDK6 gene, or some other mechanism, is
      responsible for the CDK6 kinase activity in these cell lines, several
      complementary analyses were performed. The CDK6 gene from each cell line was
      examined for mutations that might affect p16INK4a binding, whereas p16INKa add
      back experiments were performed with CDK6 immune complexes to assess p16INK4a
      function. A bona fide CDK6 mutation that disrupts p16INK4a binding and prevents
      inhibition of CDK6 protein kinase activity was identified in 1 of 17
      neuroblastoma cell lines. The mechanism(s) responsible for disruption of p16INK4a
      inhibitory activity in the remaining cell lines is unknown, but these results
      suggest that neuroblastoma cells may bypass the cell cycle block imposed by
      constitutive expression of wild-type p16INK4a in novel ways.

PMID- 9635590
TI  - Cigarette smoke induces DNA deletions in the mouse embryo.
AB  - Cigarette smoking causes cancer and DNA mutations. However, long-term chronic
      exposure to smoke is believed to be necessary for carcinogenesis. Here, we
      investigate the relationship between short-term exposure to smoke and the
      frequency of deletions in the mouse embryo. Deletions and other genome
      rearrangements are associated with carcinogenesis and inheritable diseases. The
      pink-eyed unstable (p(un)) mutation in the C57BL/6J mouse is the result of
      internal duplication of 70 kb of DNA within the p gene. Spontaneous reversion
      events in homozygous p(un)/p(un) mice occur by deletion of one copy of the
      duplicated sequence. Reversion events occurring in the embryonic premelanocytes
      of the developing fetus give rise to black spots on the gray fur of the offspring
      after birth. We investigated the effects of exposure of pregnant p(un) mice to
      cigarette smoke and cigarette smoke condensate (CSC) on the frequency of black
      spots occurring in the offspring. Pregnant dams were exposed (whole body) to
      smoke generated by either filtered or unfiltered cigarettes for 4 h, or
      alternatively, mice were given a 15 mg/kg dose of CSC during their 10th day of
      gestation. TPM, CO concentration, and plasma nicotine and cotinine levels were
      determined to characterize the smoke exposure. There was a significant increase
      in the number of DNA deletions in the embryo as evidenced by spotted offspring in
      both smoke-exposed groups and in the CSC group. These results suggest that
      embryos are highly sensitive to the genotoxic activity of cigarette smoke
      following a single exposure of only 4 h.

PMID- 9635591
TI  - The G2 block induced by DNA damage: a caffeine-resistant component independent of
      Cdc25C, MPM-2 phosphorylation, and H1 kinase activity.
AB  - Treatment of cells with agents that cause DNA damage often results in a delay in
      G2. There is convincing evidence showing that inhibition of p34cdc2 kinase
      activation is involved in the DNA damage-induced G2 delay. In this study, we have
      demonstrated the existence of an additional pathway, independent of the p34cdc2
      kinase activation pathway, that leads to a G2 arrest in etoposide-treated cells.
      Both the X-ray-induced and the etoposide-induced G2 arrest were associated with
      inhibition of the p34cdc2 H1 kinase activation pathway as judged by p34cdc2 H1
      kinase activity and phosphorylation of cdc25C. Caffeine treatment restored these
      activities after either of the treatments. However, the etoposide-treated cells
      did not resume cycling, revealing the presence of an alternative pathway leading
      to a G2 arrest. To explore the possibility that this additional pathway involved
      phosphorylation of the MPM-2 epitope that is shared by a large family of mitotic
      phosphoproteins, we monitored the phosphorylation status of the MPM-2 epitope
      after DNA damage and after treatment with caffeine. Phosphorylation of the MPM-2
      epitope was depressed in both X-ray and etoposide-treated cells, and the
      depression was reversed by caffeine in both cases. The results indicate that the
      pathway affecting MPM-2 epitope phosphorylation is involved in the G2 delay
      caused by DNA damage. However, it is not part of the caffeine-insensitive pathway
      leading to a G2 block seen in etoposide-treated cells.

PMID- 9635592
TI  - Isolation and partial characterization of a cDNA encoding a rabbit liver
      carboxylesterase that activates the prodrug irinotecan (CPT-11).
AB  - We have isolated a cDNA encoding a rabbit carboxylesterase (CE; EC 3.1.1.1) that
      converts the camptothecin-derived prodrug irinotecan (CPT-11) to the potent
      topoisomerase I inhibitor 7-ethyl-10-hydroxycamptothecin. NH2-terminal amino acid
      sequencing of a purified rabbit CE allowed the design of redundant
      oligonucleotides to perform PCR from rabbit liver cDNA. DNA sequencing of the PCR
      product confirmed the identity of the clone, and after both 5' and 3' rapid
      amplification of cDNA ends, oligonucleotide primers were designed to amplify the
      entire cDNA. The 1698-bp open reading frame encoded a 565-amino acid protein
      containing the characteristic CE B-1 and B-2 motifs, a hydrophobic NH2-terminal
      leader sequence, and the COOH-terminal residues HIEL that are thought to be
      responsible for protein localization in the endoplasmic reticulum. Transient
      expression of the cDNA in COS-7 cells resulted in CE activity in cell extracts
      and increased the sensitivity of cells to CPT-11. Additionally, stable expression
      of the rabbit liver CE cDNA in the human glioma U-373 MG cell line resulted in a
      56-fold decrease in the IC50 value for CPT-11, whereas the expression of a human
      alveolar macrophage cDNA encoding a highly homologous CE produced no change in
      drug sensitivity.

PMID- 9635593
TI  - Significant expression of vascular endothelial growth factor/vascular
      permeability factor in mouse ascites tumors.
AB  - Vascular endothelial growth factor (VEGF), also known as vascular permeability
      factor, is believed to be a potent mediator of peritoneal fluid accumulation and
      angiogenesis and of tumor growth in ascites tumor. Such roles, however, have not
      been generally established because of insufficient quantitative and systemic
      analyses. To address this, we examined the expression of VEGF in 13 mouse ascites
      tumors (5 sarcomas, 3 carcinomas, 2 lymphomas, 1 leukemia, 1 mastocytoma, and 1
      plasmacytoma). Using a newly developed sensitive and specific radioreceptor
      binding assay and functional assays, we found that active VEGF was significantly
      accumulated (6-850 ng/ml) in the ascites fluids of all 13 tumors. VEGF
      concentrations are higher in the tumors of sarcoma and carcinoma origin (430.4 +/
      234.2 ng/ml) than in those of lymphoma and hematological tumor origin (19.2 +/-
      10.45 ng/ml). VEGF that accumulated in the peritoneal fluids or expressed in the
      ascites tumor cells was easily visualized with immunoprecipitation Western blot
      analysis with a rough correlation to the expression levels of VEGF gene in these
      tumor cells, suggesting that the tumor cells, at least in part, contributed to
      the production of the VEGF that accumulated in the ascites fluid. Most ascites
      tumors expressed VEGF; the 164-amino acid isoform was predominant, the 120-amino
      acid isoform was less abundant, and the 188-amino acid isoform was least
      abundant. Several representative ascites tumors expressed similar, if not higher,
      levels of VEGF when they were cultured at normoxic states, suggesting that they
      expressed VEGF at high levels in a constitutive manner. The microvessel densities
      in the peritoneal walls of tumor-bearing mice, which are significantly higher
      than those in normal mice, basically correlated to but did not parallel the VEGF
      concentrations in their respective ascites fluids. Thus, a complicated
      relationship may exist between the VEGF production and angiogenesis associated
      with ascites tumor in vivo. Taken together, our observations suggest that VEGF
      plays a fundamental role in ascites tumor formation; however, its importance may
      vary according to tumor origin.

PMID- 9635594
TI  - Systemic treatment with a recombinant erbB-2 receptor-specific tumor toxin
      efficiently reduces pulmonary metastases in mice injected with genetically
      modified carcinoma cells.
AB  - Receptor-mediated targeted tumor therapy is an important applied consequence of
      the studies on the genetic causes of cancer. These therapy concepts have to be
      evaluated in novel animal models that reflect the molecular aberrations found in
      human tumors. Here we introduce an animal model that allows the evaluation of
      drugs directed against a surface receptor that is frequently altered in primary
      human adenocarcinomas. Tumor toxins are polypeptides in which a tumor cell
      specific recognition domain and a toxic effector domain have been joined by DNA
      recombination in vitro. Tumor cell recognition is contributed by a single-chain
      antibody domain specific for the extracellular domain of the erbB-2 receptor
      [scFv(FRP5)] and cytotoxicity by the enzymatically active domain of a bacterial
      exotoxin (exotoxin A from Pseudomonas aeruginosa). The erbB-2 receptor is
      overexpressed in many primary human cancer cells and is a favorable target for
      directed tumor therapy. The fusion protein scFv(FRP5)-exotoxin A has previously
      been shown to be able to efficiently and specifically kill erbB-2 receptor
      expressing tumor cells. We have investigated the potential of this tumor toxin to
      detect and eliminate metastasizing tumor cells upon systemic administration.
      Murine renal carcinoma cells genetically modified with human erbB-2 receptor and
      bacterial beta-galactosidase genes form large pulmonary metastases when injected
      into the tail vein of BALB/c mice. Administration of the tumor toxin over a 10
      day time period starting 1 day after tumor cell transplantation totally
      suppressed the formation of metastases. The treatment of animals 11 days after
      tumor cell transplantation, allowing the establishment of many pulmonary
      metastases, led to a drastic reduction in their number and size.

PMID- 9635595
TI  - Expression and secretion of neuroleukin/phosphohexose isomerase/maturation factor
      as autocrine motility factor by tumor cells.
AB  - The results obtained from fragmented protein microsequencing have suggested that
      autocrine motility factor (AMF), a tumor-secreted Mr 55,000 cytokine that
      regulates cell motility in vitro as well as invasion and metastasis in vivo, is
      the neuroleukin (NLK)/phosphohexose isomerase (PHI)/maturation factor (MF)
      polypeptide. Here, we cloned, sequenced, and studied the expression, secretion,
      and distribution of AMF/NLK/PHI/MF in neoplastic and their normal counterpart
      cells. Although both normal and neoplastic cells express the gene product,
      overexpression associated with selective secretion of the protein was observed
      only in tumor cells. The cDNA sequences of AMF/NLK/PHI/MF found in both human
      cancer and normal cells were found to be identical, suggesting that its secretion
      by neoplastic cells is independent of mutation or alternative splicing.
      Immunohistochemical visualization has depicted AMF/NLK/PHI/MF to be localized
      into tubular-like vesicles, diffusely distributed throughout the cytoplasm and
      not colocalized with any particular cytoskeletal network. Confocal microscopic
      imaging had shown a partial colocalization between AMF and its receptor (Mr
      78,000 glycoprotein), especially on the malignant cell surface periphery. The
      results suggest that extracellular AMF activity may be a result of the product of
      intracellular cleavage of a precursor polypeptide, which is overexpressed and
      selectively secreted through a nonclassical secretory mechanism by neoplastic
      cells.

PMID- 9635596
TI  - Genetic modulation of neu proto-oncogene-induced mammary tumorigenesis.
AB  - Modulation of oncogene-induced carcinogenesis by secondary mutation or genetic
      background may be an important factor in determining the expression of the tumor
      phenotype. We have investigated the role of loss of function mutations and strain
      specific genetic elements in the modulation of oncogene-induced breast cancer
      using a murine model. FVB female mice transgenic for the rat neu proto-oncogene
      [mouse mammary tumor virus (MMTV)-neu] developed mammary tumors between 7 and 12
      months of age, whereas FVB x C57Bl/6 (F1) MMTV-neu mice had tumor latencies
      greater than 18 months. The expression level of the neu transgene was equivalent
      in tumor tissue from both FVB and F1 mice. Furthermore, increased tumor latency
      did not appear to be associated with a decrease in expression of the neu
      transgene in the normal mammary gland of F1 mice because immunohistochemical
      staining for neu expression in the mammary glands of 3-month-old virgin female
      mice revealed similar levels of protein expression in FVB and F1 animals. When F1
      animals were backcrossed one generation onto the FVB strain ([FVB x B6] F1 x
      FVB), a subset of the resulting offspring developed tumors with a latency
      equivalent to that of the pure-strain FVB mice. Statistical analysis of the
      genetic variability in mammary tumor latency indicated that approximately three
      independent genes were involved in the latency effect. Interestingly, when tumor
      growth rates were compared in these same animals, F1 mice had significantly
      faster tumor growth rates compared with FVB mice.

PMID- 9635597
TI  - Antiapoptotic effect of ectopic TAL1/SCL expression in a human leukemic T-cell
      line.
AB  - Aberrant expression of TAL1 occurs frequently in human T-cell acute lymphoblastic
      leukemia. The effect of TAL1 expression in the T-cell lymphoid precursor,
      however, remains unclear. In the current study, we have developed TAL1 stable
      transfectants in a human immature T-cell lymphoid cell line. Whereas no effect on
      proliferation, cell culture density, or cell cycle was detected, the
      transfectants were more resistant than the parental cell line to apoptosis
      induced by chemotherapeutic agents including etoposide, daunorubicin,
      doxorubicin, cytosine arabinoside, methotrexate and vincristine and also to
      apoptosis induced by Fas/CD95 cross-linking. This effect was independent of the
      cytostatic effects of the drugs. The basic domain-deleted transfectants did not
      demonstrate altered sensitivity, suggesting that DNA binding was necessary for
      resistance to apoptosis. The ability to alter the response to a wide range of
      cell death-inducing stimuli suggests that TAL1 acts at a late stage of the
      apoptotic cascade. These data therefore provide direct evidence of an
      antiapoptotic effect of ectopic TAL1 expression in response to cytotoxic agents,
      thus providing insight into its oncogenic function in T-cell acute lymphoblastic
      leukemia and a novel experimental model to further investigate the underlying
      mechanisms. These data also have potential practical significance for cytotoxic
      therapy of this disorder.

PMID- 9635598
TI  - Effects of GLP-1 on gastric emptying, antropyloric motility, and transpyloric
      flow in response to a nonnutrient liquid.
AB  - Glucagon-like polypeptide 1 (GLP-1) may be a major enterogastrone, slowing
      gastric emptying when released by intestinal nutrients. In six conscious dogs, we
      studied the effects of GLP-1, on antropyloric motility, gastric emptying, and
      transpyloric flow after instillation of 500 ml of saline into the stomach. The
      meal was given and recordings were started 15 min after intravenous bolus and
      infusion of either saline or three different doses of GLP-1. Intravenous GLP-1
      produced a dose-related retardation of gastric emptying associated with a
      decrease in the number and volume of flow pulses in comparison to saline. This
      change in transpyloric flow was associated with an inhibition of antropyloric
      pressure waves, a stimulation of isolated pyloric pressure waves, and an increase
      in basal pyloric tone induced by intravenous GLP-1 infusion. Our findings show
      that GLP-1 has a potent dose-dependent inhibitory effect on transpyloric flow and
      gastric emptying. This effect is temporally associated with inhibition of antral
      "pumping" and stimulation of pyloric "braking" mechanisms.

PMID- 9635599
TI  - Relationships between gastric emptying and intestinal absorption of nutrients and
      energy in mini pigs.
AB  - Little is known about the relationship between gastric emptying of nutrients
      regulated by feedback mechanisms and the absorptive capacity of the gut.
      Therefore, we wanted to elucidate these interrelationships. A 150-cm jejunal
      segment was perfused (1-8 kcal/min) with three different nutrient solutions
      (either 60% of energy as carbohydrate, or 60% as protein, or 33.3% of each
      nutrient). In separate experiments, gastric emptying was measured after
      administration of three different meals with the same nutrient composition as the
      perfusion solutions. The jejunal absorption of carbohydrate, protein, fat, and
      energy demonstrated saturation kinetics. The kinetics differed among the three
      nutrients; carbohydrates were absorbed at higher rates than fat and protein.
      Interactions among the nutrients altered the kinetics providing a constant
      absorption of energy. After meals, the stomach emptied equal amounts of energy
      despite large variations in meal composition. The available intestinal absorptive
      capacity for protein was utilized by 96%, whereas that for carbohydrate, fat and
      energy were utilized only by 46-62%. Besides reserves in the absorptive capacity,
      the intestine provided reserves in total length available for absorption. The
      results indicate a close relationship between the energy-dependent absorption of
      nutrients and the energy-dependent feedback inhibition of gastric emptying.

PMID- 9635600
TI  - Role of gastric emptying in functional dyspepsia: a scintigraphic study of 94
      subjects.
AB  - Many physiological factors can alter gastric emptying, and the role of gastric
      emptying in functional dyspepsia is controversial. The aim of this study was to
      assess the effects of different factors (age, sex, the degree of dyspeptic and
      irritable bowel symptoms, lactase deficiency, smoking habits, the use of
      antiinflammatory drugs, and H. pylori gastritis) on gastric emptying in patients
      with functional dyspepsia. The study population consisted of 83 patients with
      functional dyspepsia and 11 control subjects who underwent a standardized
      scintigraphic examination to study gastric emptying. This study detected no
      difference in gastric emptying between different subgroups with functional
      dyspepsia. There was, however, a slight tendency for delayed gastric emptying
      among patients with functional dyspepsia compared to controls. Intragastric
      distribution of the solid content was more distally located in smokers, and the
      solid lagtime was prolonged among antiinflammatory drug users. The gastric
      emptying of liquids was delayed among older patients. The subgrouping of
      dyspeptic symptoms is of minor importance with respect to gastric emptying.
      Habitual smoking and the use of antiinflammatory drugs are potent factors able to
      alter the gastric emptying of solids, but the role of H. pylori seems to be less
      important.

PMID- 9635601
TI  - Transient impact of hemodialysis on gastric myoelectrical activity of uremic
      patients.
AB  - Upper gastrointestinal discomforts are common in uremic patients. Investigators
      have stressed the structural, histopathological, and physiological changes in the
      gastrointestinal tract in the past decades. Few data are available about the
      electrophysiological changes in the stomach of uremic patients. It is not known
      whether hemodialysis alters gastric myoelectrical activity. More interestingly,
      what is the long-term effect? To address these questions, we measured gastric
      myoelectrical activity before and after hemodialysis in patients with end-stage
      renal disease on maintenance dialysis treatment. Twenty-one uremic patients with
      dyspeptic complaints were enrolled in this study. Gastric myoelectrical activity
      was measured noninvasively using abdominal surface electrodes
      (electrogastrography). The paired variables obtained before and after
      hemodialysis were compared statistically. We also compared the difference between
      two subgroups defined as new hemodialysis patients and chronic hemodialysis
      patients. We found that there was a significantly lower percentage of normal slow
      wave frequency obtained after hemodialysis in comparison with before hemodialysis
      (fasting state: 49.1 +/- 4.8% vs 68.1 +/- 5.4%, P < 0.01; fed state: 53.8 +/-
      6.9% vs 73.4 +/- 4.1%, P < 0.01). In comparing the subgroups, there were no
      differences between each EGG variable. We concluded that the hemodialysis itself
      compromised gastric myoelectrical activity in its immediate effect. However,
      there were no permanent effects regarding gastric myoelectrical activity itself.

PMID- 9635602
TI  - Effect of capsaicin-containing red pepper sauce suspension on upper
      gastrointestinal motility in healthy volunteers.
AB  - Afferent nerves play a major role in the regulation of gastrointestinal motility.
      The questions remains if specific food ingredients can selectively activate such
      fibers. The aim of the study was to investigate the effect of intraesophageal
      application of a capsaicin-containing red pepper sauce (Tabasco) suspension on
      upper gastrointestinal motility in a controlled trial. After a baseline recording
      [esophageal motility, balloon distension, electrogastrogram (EGG)], red pepper or
      saline solution was infused intraesophageally in seven healthy volunteers. At 30
      min gastric emptying and orocecal transit time were determined using a
      [13C]acetate and H2-lactulose breath test. Infusion of red pepper sauce
      suspension significantly increased the amplitudes (65.8 +/- 3 to 78.5 +/- 4.7 mm
      Hg, P < 0.05) and propagation velocity (2.9 +/- 0.3 to 4.25 +/- 0.3 sec, P <
      0.05) of esophageal pressure waves and LES pressure (17.8 +/- 1.4 to 23.7 +/- 2.6
      mm Hg, P < 0.05). It significantly decreased perception and discomfort threshold
      of intraesophageal balloon distension, reduced the percentage of normal
      electrical activity in the EGG, and delayed gastric emptying (saline: T(1/2) 42.9
      +/- 12.0 min vs red pepper: T(1/2) 66.8 +/- 19.0 min, P < 0.05). Despite the
      prolongation of gastric emptying, orocecal transit time was not altered,
      indicating an actual increase of intestinal transit. Esophageal application of
      capsaicin-containing red pepper sauce suspension had profound changes on upper
      gastrointestinal motility, which could improve clearance and protection of the
      esophagus and could lead to retention of the irritant in the stomach and faster
      transit through the small bowel.

PMID- 9635603
TI  - Double-blind, placebo-controlled study on effects of diclofenac sodium and
      indomethacin on postprandial gastric motility in man.
AB  - Data from animal studies suggest that NSAIDs-induced gastric damage may be due to
      increased gastric motility. Such a mechanism, however, has never been tested or
      demonstrated in man. We evaluated the effects of two frequently prescribed
      NSAIDs, indomethacin and diclofenac sodium, on postprandial gastric motor
      activity (a physiologically reproducible stimulus) in healthy volunteers to see
      whether these compounds increase gastric motility. Twenty-four healthy volunteers
      of both sexes, 21-35 years of age, underwent a basal gastric motility recording.
      Thereafter, they were randomized in three groups to receive either placebo,
      indomethacin (50 mg three times a day) or diclofenac sodium (50 mg three times a
      day) for a week. At the end of the week, they underwent an identical manometric
      study. Analysis of the motility tracings showed no difference in gastric antral
      motility index and in amplitude of gastric antral contractions after NSAIDs with
      respect to the basal study and to the placebo group. About 50% of subjects (two
      in the placebo group) complained of side effects. These were transient and mild,
      except in two subjects taking indomethacin, in whom endoscopy was necessary; one
      of these had a small prepyloric ulcer. It is concluded that in man NSAID-related
      gastric damage is unlikely to be due to increased gastric motility.

PMID- 9635604
TI  - Giant gastric ulcers and risk factors for gastroduodenal mucosal disease in
      orthotopic lung transplant patients.
AB  - Giant gastric ulcers are defined as ulcers with a diameter greater than 3 cm.
      Previously they have not been described in lung transplant recipients. We report
      a high incidence of symptomatic giant gastric ulcers and identify the risk
      factors for ulcer development in these patients. We examined the records of all
      95 patients who had undergone lung transplantation at our institution from
      November 1991 to July 1995. Fourteen of the patients who underwent lung
      transplantation developed symptoms that required esophagogastroduodenoscopy.
      Three of these patients (21%) were found to have giant gastric ulcers. The
      relative risk of giant gastric ulcer in symptomatic patients undergoing endoscopy
      after lung transplantation is over 40 times that of population controls. The
      patients who developed giant gastric ulcers, despite H2 antagonist use, had all
      received bilateral lung transplantation and had received nonsteroidal
      antiinflammatory drugs, cyclosporine, and high-dose intravenous corticosteroids.
      The risk of developing giant gastric ulcers is significantly increased in
      patients who have undergone bilateral orthotopic lung transplantation. Clinicians
      should be made aware of this complication in order to avoid use of ulcerogenic
      medications in this population. Avoidance of these medications could potentially
      minimize the risk of this complication.

PMID- 9635605
TI  - Effectiveness of lamivudine in treatment of acute recurrent hepatitis B after
      liver transplantation.

PMID- 9635606
TI  - Oral ganciclovir usage for cytomegalovirus prophylaxis in organ transplant
      recipients: is emergence of resistance imminent?

PMID- 9635607
TI  - Optical biopsy in human pancreatobiliary tissue using optical coherence
      tomography.
AB  - Optical coherence tomography (OCT) is a new technique for performing high
      resolution, cross-sectional tomographic imaging in human tissue. OCT is analogous
      to ultrasound B mode imaging except that it uses light rather than acoustical
      waves. As a result, OCT has over 10 times the resolution of currently available
      clinical high-resolution cross-sectional imaging technologies. In this work, we
      investigate the capability of OCT to differentiate the architectural morphology
      of pancreatobiliary tissues. Normal pancreatobiliary tissues, including the
      gallbladder, common bile duct, pancreatic duct, and pancreas were taken
      postmortem and imaged using OCT. Images were compared to corresponding histology
      to confirm tissue identity. Microstructure was delineated in different tissues,
      including tissue layers, glands, submucosal microvasculature, and pancreatic
      islets of Langerhans. The ability of OCT to provide high-resolution imaging of
      pancreatobiliary architectural morphology suggests the feasibility of using OCT
      as a powerful diagnostic endoscopic imaging technology to image early stages of
      pancreatobiliary disease.

PMID- 9635608
TI  - Adenomyoma of the distal common bile duct mimicking cholangiocarcinoma.

PMID- 9635609
TI  - Human proximal duodenal alkaline secretion is mediated by Cl-/HCO3- exchange and
      HCO3- conductance.
AB  - The proximal duodenal epithelium secretes bicarbonate into an adherent mucus
      layer, thereby protecting the mucosa from injury by gastric acid and pepsin.
      While bicarbonate secretion is stimulated and inhibited by a number of agonists
      and antagonists, the apical anion transport pathways have not been addressed
      fully. The objective was to assess if apical Cl-/HCO3- exchange and Cl-:HCO3-
      conductance are involved in duodenal mucosal bicarbonate secretion (DMBS). In
      healthy volunteers, the proximal 4 cm of duodenum was isolated, perfused with
      either saline or 4,4'-diisothiocyano-2,2'-disulfonic acid (DIDS), and bicarbonate
      secretion and transepithelial potential difference (PD) were stimulated by either
      PGE2 or the phosphodiesterase inhibitor theophylline to increase cyclic AMP.
      Luminal DIDS abolished PGE2-stimulated DMBS, yet had no effect on the increase in
      PD and failed to significantly alter theophylline-induced DMBS and PD. Therefore,
      in human proximal duodenum, it appears that PGE2 and cAMP activate distinct HCO3-
      transport pathways likely involving a DIDS-sensitive Cl-/HCO3- exchanger and DIDS
      insensitive HCO3- conductance.

PMID- 9635610
TI  - Identification of H. pylori in saliva by a nested PCR assay derived from a newly
      cloned DNA probe.
AB  - A novel probe was developed from genomic DNA of Helicobacter pylori ATCC type
      strain 43629. It hybridized with all 73 H. pylori clinical isolates tested but
      not with any of 183 non-H. pylori DNAs in dot blot hybridization. Typing tests
      revealed 41 different HaeIII-digestion patterns from 57 H. pylori strains tested.
      Based on the sequence of the probe, a nested PCR was developed that detected as
      little as 2 fg of H. pylori DNA or approximately equivalent to one cell. No PCR
      products were amplified from any of 21 non-H. pylori strains tested. Using this
      nested PCR, H. pylori DNA was detected in 33 of 45 (73%) saliva samples collected
      from patients with gastric H. pylori infection. These data suggest that the probe
      is useful for typing H. pylori and that the nested PCR is a valuable tool for
      detecting H. pylori DNA in saliva.

PMID- 9635611
TI  - Helicobacter pylori infection and peptic ulcer disease in cirrhosis.
AB  - An increased frequency of peptic ulcer disease is noted in patients with
      cirrhosis, but the role of H. pylori in this disorder remains to be determined.
      The diagnosis of cirrhosis was confirmed by a combination of clinical,
      biochemical, radiological, and histological methods. The severity of cirrhosis
      was assessed by Pugh's modification of Child's criteria. Upper gastrointestinal
      endoscopy was performed consecutively to evaluate the presence of varices and
      gastroduodenal mucosa. H. pylori status was assessed by histology, urease test,
      and serology. In all, 130 patients with cirrhosis were recruited into the study;
      there were 86 males and 44 females with a mean (SD) age of 54.4 (12.7) years. The
      H. pylori prevalence was 76.2%. There was no difference in age between the H.
      pylori-positive and -negative cirrhotics (P = 0.29). The H. pylori prevalence
      revealed no difference among cirrhotics with Child A (77.8%), Child B (72.9%),
      and Child C (78.6%) (P = 0.8), and neither was there a difference in H. pylori
      prevalence in cirrhotics with and without congestive gastropathy (77% vs 73.7%, P
      = 0.84). The prevalence of H. pylori in cirrhotics with and without varices did
      not show a statistical difference (75% vs 81.8%, P = 0.68). There also was no
      difference in the H. pylori prevalence between cirrhotic patients with and
      without peptic ulcers (84.4% vs 69.7%, P = 0.09). In conclusion, the prevalence
      of H. pylori or peptic ulcer is independent of the severity of cirrhotic liver
      disease. The association between H. pylori infection and peptic ulcer disease is
      weak in cirrhosis.

PMID- 9635612
TI  - Beneficial effects of Helicobacter pylori eradication on idiopathic chronic
      urticaria.
AB  - Helicobacter pylori, the most important cause of gastritis and peptic ulcer,
      recently has been associated with several extradigestive diseases. The aim of
      this study was to assess the prevalence of Helicobacter pylori infection and the
      effects of bacterium eradication in 42 consecutive patients affected by
      idiopathic chronic urticaria. Helicobacter pylori was assessed by [13C]urea
      breath test. Amoxicillin, clarithromycin, and lansoprazole were given to infected
      patients for seven days. Urticaria and gastrointestinal symptoms were assessed on
      enrollment and after eradication. Fifty-five percent of patients proved to be
      infected by Helicobacter pylori. Prevalence of gastrointestinal symptoms did not
      differ between infected and uninfected patients. Eighty-eight percent of infected
      patients in whom the bacterium was eradicated after therapy showed a total or
      partial remission of urticaria symptoms. Conversely, symptoms remained unchanged
      in all uninfected patients. In conclusion, Helicobacter pylori affects a high
      percentage of patients with idiopathic chronic urticaria; however, typical
      gastrointestinal symptoms do not identify infection status. Bacterium eradication
      is associated with a remission of urticaria symptoms, suggesting a possible role
      of Helicobacter pylori in the pathogenesis of this skin disorder.

PMID- 9635613
TI  - In vitro wound repair by human gastric fibroblasts: implications for ulcer
      healing.
AB  - Fibroblasts modulate epithelial biological activities and play a key role in the
      ulcer healing process. There is no information regarding the biological response
      of human gastric fibroblasts to regulatory compounds. The aim of this study was
      to assess the effects of growth factors and prostaglandins on an in vitro model
      of human gastric fibroblast wound repair. Subconfluent fibroblast cultures were
      used to study proliferative responses, determined by [3H]thymidine incorporation
      into DNA. In vitro wound repair was determined in confluent fibroblast monolayers
      after mechanical denudation. The presence of putative growth factors secreted by
      fibroblasts was studied in conditioned medium by heparin-affinity chromatography
      and immunodetection with specific antibodies. Serum and platelet-derived growth
      factor (PDGF) -BB induced a dramatic increase in both gastric fibroblast
      proliferation and closure of wounded cell monolayers, whereas these activities
      were inhibited by both transforming growth factor (TGF) -beta1 and prostaglandin
      E1. Basal activities in unstimulated gastric fibroblasts were lower than those
      obtained in skin fibroblasts. Conditioned medium stimulated fibroblast
      proliferation and wound repair activity, which was inhibited by the addition of
      suramin, and was partially dependent on the presence of PDGF-like factor. PDGF is
      a major, autocrine promotor of human gastric fibroblast-dependent wound repair
      activities, which are inhibited by prostaglandins and TGF-beta. These findings
      might be important for future therapeutic ulcer healing approaches.

PMID- 9635614
TI  - Treating nonulcer dyspepsia considering both functional disorders of the
      digestive system and psychiatric conditions.
AB  - Nonulcer dyspepsia (NUD) is a common syndrome, but the optimal treatments have
      yet to be established. This study was performed to determine the most effective
      treatment for NUD. Subjects were recruited through the Department of General
      Internal Medicine at the Kyushu University Hospital because of their somatic
      symptoms. When no organic lesions were found, the patients were directed to
      consult our department (Psychosomatic Medicine); 194 consecutive NUD patients
      were studied. All subjects were assessed psychiatrically with the Structured
      Clinical Interview for DSM-III-R(SCID). Patients with serious NUD were
      hospitalized, and randomly divided into control (N = 42) and experimental groups
      (N = 86). The controls were treated with physical treatment alone. The
      experimental group received psychiatric treatment in addition, based on the
      results of SCID. The experimental group showed a significant improvement compared
      with the controls (P < 0.0001). The treatment for NUD taking into consideration
      both the physical and psychiatric conditions is highly effective.

PMID- 9635615
TI  - Histological study of mechanisms of adaptive cytoprotection on ethanol-induced
      mucosal damage in rat stomachs.
AB  - Adaptive cytoprotection in the gastric mucosa could be induced by exposure to low
      concentrations of noxious agents. However, experimental results reported so far
      were based on macroscopic studies. We aimed to investigate the phenomenon of
      gastric adaptive cytoprotection of mild irritants and its correlation with
      intramucosal mucus at the histological level. It was found that histological
      damage induced by ethanol had a negative correlation with the length of the mucus
      secreting layer in the gastric mucosa. Mild irritants such as 20% ethanol and 5%
      NaCl preserved the 100% ethanol-induced intramucosal mucus depletion, but only
      the former agent demonstrated a cytoprotective effect against the histological
      damage, indicating that preservation of intramucosal mucus may not necessarily
      play a permissive role in adaptive cytoprotection. The capsaicin-sensitive
      sensory afferent neurons, sensory chemoreceptors, muscarinic receptors, alpha2
      adrenoceptors and peripheral dopamine D2-receptors were found to be the
      components of the autonomic nervous system involved in the cytoprotective
      processes of 20% ethanol. Endogenous mediators including nitric oxide,
      prostaglandins, and possibly nonprotein sulfhydryl compounds also seemed to
      participate in such protection. Nevertheless, 0.3 M HCl did not show any effect
      either on mucosal damage or depletion of intramucosal mucus induced by absolute
      ethanol. These findings suggest that only 20% ethanol shows histological
      cytoprotection, which would involve various components of the autonomic nervous
      system and endogenous mediators. Furthermore, this investigation also implies a
      new perspective: that in order to study a true adaptive cytoprotection,
      histological examination of the gastric mucosa should be performed.

PMID- 9635616
TI  - Adenosine protects against indomethacin-induced gastric damage in rats.
AB  - This study examines the putative gastroprotective effect of adenosine on
      indomethacin-induced gastric lesions and the possible mechanisms involved. After
      24 hr of starvation, the rats were treated either with indomethacin (Indo; 25
      mg/kg, subcutaneously) alone or adenosine + Indo (Ado; 7.5 mg/kg, subcutaneously,
      three times a day), or the vehicle (5% NaHCO3, subcutaneously). The length of
      hemorrhagic lesions in the stomachs was expressed as the lesion index. The tissue
      associated myeloperoxidase (MPO) activity and protein oxidation were measured in
      gastric tissue samples. Formation of reactive oxygen species in gastric tissues
      was measured by using luminol- and lucigenin-enhanced chemiluminescence. In other
      groups of rats, gastric mucosal permeability and gastric acid output were
      performed following the same treatment regimens. The gastric mucosal permeability
      was measured by determination of [51Cr]EDTA clearance in a perfused stomach
      preparation and gastric acid secretion studies were performed following pylorus
      ligation. The lesion index, the increase in lucigenin-enhanced chemiluminescence,
      and the increase in gastric mucosal permeability in Indo-treated rats were
      reversed by Ado pretreatment. Ado pretreatment also prevented the increase in
      gastric acid output and gastric volume in Indo-treated rats. Thus, these findings
      implicate that exogenous adenosine has a protective role on indomethacin-induced
      gastric lesions, possibly by inhibiting gastric hyperacidity and reactive oxygen
      formation and by preventing disruption of the mucosal integrity.

PMID- 9635617
TI  - Mechanism of enhancement of intestinal ulcerogenicity of S-aryl propionic acids
      by their R-enantiomers in the rat.
AB  - We previously observed a marked increase in gastrointestinal toxicity of rac
      flurbiprofen compared to the therapeutically equivalent dose of the S enantiomer.
      This paper quantitates these observations and examines the mechanism by which
      this paradoxical toxicity occurs. We have evaluated the ulcer scores, mucosal
      neutrophil infiltration, by immunostaining of CD11/18 antigen, and mucosal
      neutrophil activity by myeloperoxidase measurement at two dose levels of (R)-,
      (S)-, and rac-flurbiprofen, administered over 30 days. Dose-response for
      intestinal ulcer production was observed for rac- and (S)-flurbiprofen; animals
      given (R)-flurbiprofen exhibited no ulcers. Yet rac-flurbiprofen proved to be
      twice as ulcerogenic as (S)-flurbiprofen. The mechanism of the exacerbation of
      gastrointestinal toxicity of (S)-flurbiprofen by the noncyclooxygenase inhibiting
      (R)-flurbiprofen is believed to be associated with its effect on ICAM-1 up
      regulation. This is followed by neutrophil adhesiveness to ICAM-1 via the LFA-1
      antigen on its surface and the extravasation of neutrophils into the tissue. We
      also examined the effect of high dose (R)-flurbiprofen vs vehicle over 15 days in
      animals in which ulcers had been produced by treatment with (S)-flurbiprofen for
      the previous 15 days. (R)-flurbiprofen did not sustain induced ulcers. The
      results of this study suggest that human studies be conducted to determine if
      enhanced gastrointestinal toxicity occurs in man. This is at issue since rac
      compounds of this class are available over the counter and others may be
      introduced.

PMID- 9635618
TI  - Gastrin-releasing peptide stimulates gallbladder motility but not sphincter of
      Oddi motility in Australian brush-tailed possum.
AB  - The neural distribution and action of gastrin-releasing peptide in the
      extrahepatic biliary tree of the Australian brush-tailed possum was investigated.
      Immunohistochemical staining of fixed specimens demonstrated gastrin-releasing
      peptide-containing nerves throughout the neural plexuses of the gallbladder,
      sphincter of Oddi, and mucosa of the common bile duct. Gastrin-releasing peptide
      (5-2000 ng/kg) increased gallbladder tone to a level equivalent to that produced
      by cholecystokinin octapeptide (160 ng/kg). This action was tetrodotoxin
      insensitive. Sphincter of Oddi motility and transsphincteric flow were not
      altered. Possible mediation of the gallbladder response by gastrin was examined.
      Gastrin (50-2500 ng/kg) stimulated gastric acid secretion, elevated gallbladder
      motility to 64% of that produced by gastrin-releasing peptide, and did not alter
      sphincter of Oddi motility. In conclusion, gastrin-releasing peptide-containing
      nerves are found in the neural plexus of the possum extrahepatic biliary tree.
      Gastrin-releasing peptide induces gallbladder contraction in part by a direct
      action on gallbladder smooth muscle and also via release of gastrin.

PMID- 9635619
TI  - Gallstone prevalence in Germany: the Ulm Gallbladder Stone Study.
AB  - The Ulm Gallbladder Stone Study is the first ultrasound-based epidemiologic
      survey of cholecystolithiasis in the former West Germany. A study population of
      1116 blood donors (656 men, age 38.0 +/- 12.0 years; 460 women, age 34.1 +/- 11.2
      years) at the Central Blood Bank of the German Red Cross in Ulm was examined
      between April 1994 and February 1995. Based on age, subjects were assigned to one
      of four groups (18-30, 31-40, 41-50, and 51-65 years). Following a structured
      interview of each study subject, an ultrasound examination was carried out and a
      blood sample obtained for laboratory study. Overall, 6.0% (95% (95% CI: 4.8%
      7.6%) of all study subjects (5.8% of the men and 6.3% of the women) exhibited
      evidence of current or past gallbladder disease (cholelithiasis or history of
      cholecystectomy). The prevalence of gallbladder disease correlated positively
      with age, reaching a maximum of 13.7% (9.5-20.0) in the 51- to 65-year-old age
      group, and also correlated as with body mass index (BMI). Female subjects with
      previous full-term pregnancies showed a higher prevalence of cholelithiasis, but
      this difference was not statistically significant for age-adjusted analysis.
      Subjects with a family history of cholelithiasis were found to suffer from
      gallstones in 11.5% (8.0-16.7) of cases compared with 4.6% (3.4%-6.3%) of
      subjects without such family history. Autopsy studies conducted in Germany have
      shown the prevalence of gallstones to be about 13.1% in men and 33.8% in women.
      Our sonographic data are relatively low in comparison. This may be due, in part,
      to the specific selection characteristics inherent in retrospective autopsy
      studies, such as age distribution and the presence of other pathologic factors
      associated with increased risk for cholelithiasis. The Ulm data rank in the lower
      third of the prevalence range reported for European sonographic studies to date.
      Age, positive family history, and increased BMI all correlated positively with
      the prevalence of gallbladder disease (P < 0.05). For the study population as a
      whole, there was no gender-specific increased risk for the development of
      gallstones.

PMID- 9635620
TI  - Adjuvant cholylsarcosine during ursodeoxycholic acid treatment of primary biliary
      cirrhosis.
AB  - We postulated that coadministration of cholylsarcosine with ursodeoxycholic acid
      might provide additional benefit to primary biliary cirrhosis patients with an
      incomplete response to ursodeoxycholic acid. Our aim was to test the tolerability
      and the effect of adjuvant cholylsarcosine on liver tests and plasma cholesterol
      in primary biliary cirrhosis patients receiving ursodeoxycholic acid. Four
      primary biliary cirrhosis patients, who, despite more than a year of
      ursodeoxycholic acid therapy, had one or more liver tests persistently equal to
      or greater than twice the upper limit of normal, received cholylsarcosine (12-15
      mg/kg/day) in addition to ursodeoxycholic acid (13-15 mg/kg/day) for six weeks in
      an open label study. Values of liver tests and plasma cholesterol, determined
      every two weeks, remained unchanged. One patient discontinued cholylsarcosine at
      week 4 because of new-onset pruritus. Analysis of duodenal bile acids in one
      patient showed 52% enrichment in cholylsarcosine and hydrophilic bile acids
      constituted 87% of total bile acids. It is concluded that the addition of
      cholylsarcosine to ursodeoxycholic acid did not influence liver tests in four
      primary biliary cirrhosis patients who had not responded completely to
      ursodeoxycholic acid alone. Cholylsarcosine was absorbed and became a dominant
      biliary bile acid; its administration was associated with increased pruritus.

PMID- 9635621
TI  - Esophageal varices in rat models of liver cirrhosis.
AB  - Animal models resembling the human situation are very useful to investigate human
      disease. However, there has been no evidence of esophageal varices in rats with
      liver cirrhosis. In the present study, to determine whether intrahepatic portal
      hypertension produced by liver cirrhosis induces esophageal varices in rats, the
      esophagus was examined endoscopically in rat models of liver cirrhosis. All rats
      given carbon tetrachloride or thioacetamide and six of seven rats given a choline
      deficient diet had esophageal varices or venous dilatation after 16 weeks of
      treatment, although the varices in one rat given carbon tetrachloride and in two
      rats given a choline-deficient diet were reduced from weeks 16 to 18. These
      findings suggest that timing is important when studying esophageal varices in rat
      models of liver cirrhosis. It is concluded that certain models of liver cirrhosis
      in rats could be used as models of esophageal varices due to intrahepatic portal
      hypertension.

PMID- 9635622
TI  - Effects on gastric circulation of treatment for portal hypertension in cirrhosis.
AB  - We evaluated the gastric circulatory effects of the type of treatment
      administered for portal hypertension. Of 14 patients with cirrhosis, seven
      received a transjugular intrahepatic portosystemic shunt (TIPS; group T) and
      seven received percutaneous transhepatic portographic embolization (PTPE; group
      P). Patients were evaluated over the course of one year. After treatment, portal
      venous pressure was significantly reduced from 39 +/- 6 cm H2O to 32 +/- 5 (P <
      0.001) in group T and was significantly elevated from 29 +/- 10 to 33 +/- 8 (P <
      0.05) in group P. The portal flow velocity (Vmean) was significantly higher in
      group T vs group P (P < 0.0001). The congestion index was significantly lower in
      group T than in group P (P < 0.0001). The gastric mucosal blood flow was
      increased in group T but was unchanged in group P. Esophageal varices showed some
      improvement in both groups, but the portal hypertensive gastropathy was improved
      only in group T. These findings help to explain the differing effects on the
      gastric circulation related to the type of treatment used for portal
      hypertension.

PMID- 9635623
TI  - Hepatitis G and C viruses respond to interferon-alpha with different virologic
      kinetics.
AB  - The aim of this work was to specify the time course of response to interferon
      (IFN) of hepatitis G virus (HGV) and hepatitis C virus (HCV) in coinfected
      individuals. A group of 33 patients, undergoing 12 months of IFN therapy for
      chronic hepatitis C, was screened for the presence of both HGV and HCV RNAs to
      select seven coinfected patients. Spontaneous recovery from HGV infection was
      excluded through the detection of antibodies to the envelope-2 protein of HGV and
      HCV isolates were genotyped. Within three months of treatment, we found that HGV
      RNA was transiently cleared in 6/7 patients, but the rate of long-term favorable
      response was very low (1/7). In addition, considering the same individuals
      separately, it was shown that HGV and HCV responded to IFN with different
      kinetics in 5/7 patients. Taken together, these results underscore the importance
      of the virological basis of the resistance to IFN treatment.

PMID- 9635624
TI  - Prognostic evaluation of early indicators in fulminant hepatic failure by
      multivariate analysis.
AB  - Viral hepatitis is the commonest cause of fulminant hepatic failure (FHF) in
      developing countries. We evaluated the early indicators of prognosis in these
      patients by multivariate analysis. The records of 204 consecutive patients with
      acute liver failure admitted with hepatic encephalopathy over five years were
      studied. The etiology of these patients included virus related in 186 (91.1%),
      drug induced in 15 (7.4%), Wilson's disease in one (0.5%), acute Budd-Chiari
      syndrome in one (0.5%), and malignant infiltration in one (0.5%). Patients with
      FHF complicating viral hepatitis were analyzed by univariate and multivariate
      analysis. These patients were further subclassified depending upon the interval
      between the onset of jaundice and the onset of encephalopathy into hyperacute
      (HALF; interval 0-7 days), acute (ALF; interval 8-28 days) and subacute liver
      failure (SALF; interval 4-12 weeks). Sixty (32.3%) patients with viral hepatitis
      survived. Univariate analysis showed that the interval between onset of
      encephalopathy and onset of jaundice, grade of encephalopathy, raised
      intracranial pressure, prothrombin time, and serum bilirubin levels on admission
      were related to outcome in these patients. Multivariate logistic regression
      analysis showed that the presence of raised intracranial pressure at the time of
      admission, prothrombin time >100 sec on admission, age (>50 yr), and onset of
      encephalopathy seven days after onset of jaundice were associated with poor
      prognosis. Forty seven (37.0%) of 129 patients with HALF survived compared with 9
      (22.5%) of 40 with ALF and 4 (21.1%) of 19 with SALF (P = NS). Raised
      intracranial pressure was more frequent in patients with HALF (48.8%) than in
      patients with ALF (32.5%) and SALF (15.8%; P = 0.01), while clinically detectable
      ascites was more frequent in patients with SALF (78.9%) compared with HALF
      (19.7%) and ALF (37.5%; P < 0.0001). The factors adversely affecting the outcome
      in our patients with FHF complicating viral hepatitis include presence of overt
      clinical features of raised ICP at the time of hospitalization, prothrombin time
      (>100 sec) on admission, age (>50 yr), and onset of encephalopathy seven days
      after onset of jaundice.

PMID- 9635625
TI  - Prognostic value of generation of growth hormone-stimulated insulin-like growth
      factor-I (IGF-I) and its binding protein-3 in patients with compensated and
      decompensated liver cirrhosis.
AB  - Our aim was to study the prognostic value of growth hormone (GH) -stimulated
      insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3)
      generation in patients with compensated [group 1 (N = 8) with a Child-Pugh (CP)
      score of 5-8] and decompensated postnecrotic liver cirrhosis [group 2 (N = 7)
      with a CP score of 9-12]. Serum levels of IGF-I, GH-binding protein (GHBP), and
      IGFBP-3 were measured before and 24 hr after a single subcutaneous injection of
      recombinant human GH (rhGH, 0.14 units/kg). Patients (mean age 56 years) were
      followed prospectively for three years. Six patients (40%) died during the follow
      up period, of whom half had a CP score <9. Mean serum IGF-I levels 24 hr after
      rhGH injection (group 1 vs group 2, 17.4 +/- 6.8 vs 7.4 +/- 0.7 nmol/liter)
      predicted survival with 93% accuracy. Levels <10 nmol/liter portended a poor
      prognosis, with 15% survival at one year, whereas levels >10 nmol/liter had a
      100% survival rate at one and two years, respectively. Baseline IGF-I (9.98 +/-
      2.0 vs 6.38 +/- 0.8 nmol/liter), GHBP (9.2 +/- 3 vs 5.7 +/- 0.8%/50 microl), and
      IGFBP-3 serum levels at baseline (1.7 +/- 0.3 vs 0.86 +/- 0.2 mg/liter) and at 24
      hr (2.04 +/- 0.38 vs 0.99 +/- 0.3 mg/liter) did not add to the predictive value
      of stimulated IGF-I levels at 24 hr and were less accurate in predicting the
      outcome in comparison to CP score (80%). We conclude that stimulated IGF-1 <10
      nmol/liter may be a true predictor of a negative prognosis in patients with liver
      cirrhosis.

PMID- 9635626
TI  - Antibodies to Ro/La, Cenp-B, and snRNPs antigens in autoimmune hepatitis of North
      America versus Asia: patterns of immunofluorescence, ELISA reactivities, and HLA
      association.
AB  - To assess whether demography is one of the important factors determining antibody
      response to nuclear antigens [ANA: SSA-Ro (52K and 60K), SSB-La, snRNPs (A, 70K,
      B'/B), and Cenp-B], we investigated 95 and 47 sera of autoimmune hepatitis (AIH)
      from North America and Asia, respectively, by immunofluorescent (IF) and
      recombinant ELISA. Correlations among nuclear IF patterns, ELISA, and disease
      indices were analyzed. The frequency and titer of individual antibodies differed
      significantly between the groups. Patients with speckled patterns were younger in
      both regions and had higher aspartate aminotransferase levels only in North
      America. HLA-A1, B8, DQ2, and DR4 or DR3 or both in North America, and A2, B61,
      DQ7, and DR4 in Asia were predominant. In Asia, B61 correlated with anti-70K, and
      DQ7 correlated with antibodies to 52K, Cenp-B, and B'/B. In North America, A1,
      B8, DR3 haplotype, and DQ2 correlated with antibodies to A and 70K. Anti-B'/B and
      DR4 in North America, and A2 in Asia, were associated with concurrent immunologic
      disorder. Individual ANA clusters correlated with individual HLA in the
      demography, and different HLA alleles might determine disease expression as well
      as different ANA being produced in AIH.

PMID- 9635627
TI  - Beer affects oxidative stress due to ethanol in rats.
AB  - The relationship between chronic moderate beer consumption and oxidative stress
      was studied in rats. Animals were fed three different isocaloric diets for six
      weeks: a beer-containing diet (30% w/w), an ethanol-supplemented diet (1.1 g/100
      g, the same as in the beer diet) and an alcohol-free basal diet. At the end of
      the feeding period, rats were analyzed for plasma and liver oxidative status.
      Some livers were isolated and exposed to ischemia-reperfusion to assess the
      additional oxidative stress determined by reperfusion. No significant differences
      in plasma antioxidant status were found among the three dietary groups.
      Lipoproteins from the beer group, however, showed a greater propensity to resist
      lipid peroxidation. Ischemia caused a decrease in liver energy and antioxidant
      status in all groups. Nevertheless, ATP was lower in the livers of rats exposed
      to the ethanol diet. During reperfusion, lipoperoxidation increased significantly
      in all groups. However, livers obtained from ethanol-treated rats showed the
      higher formation of lipoperoxides. In conclusion, a moderate consumption of beer
      in a well-balanced diet did not appear to cause oxidative stress in rats;
      moreover, probably through its minor components, beer could attenuate the
      oxidative action of ethanol by itself.

PMID- 9635628
TI  - Rapid diagnostic test for detection of Cys282Tyr mutation in hereditary
      hemochromatosis.

PMID- 9635629
TI  - Collagenous colitis and Yersinia enterocolitica infection.
AB  - Collagenous colitis is a rare clinical and pathological entity characterized by
      watery diarrhea and deposition of collagen beneath the surface epithelium of the
      colon. Its etiology is unknown. We present a careful retrospective
      clinicopathological analysis of six patients with collagenous colitis diagnosed
      at our hospital during a three-year period. Three of the patients had had a
      Yersinia enterocolitica infection, detected by stool culture and elevated serum
      antibody titers, preceding the diagnosis of collagenous colitis. Four patients
      had duodenal villous atrophy, which in two patients was refractory to a gluten
      free diet. We propose that Yersinia enterocolitica infection may be a triggering
      factor for the development of collagenous colitis in some cases. Duodenal villous
      atrophy not responding to gluten withdrawal is common in association with
      collagenous colitis.

PMID- 9635631
TI  - Activated protein C resistance, thrombophilia, and inflammatory bowel disease.
AB  - Thromboembolic events frequently complicate the clinical course of patients with
      inflammatory bowel disease (IBD). Hereditary thrombophilia may contribute to this
      tendency. Resistance to activated protein C is the most recently described
      thrombophilic state and may account for up to 40% of patients with thrombophilia.
      Thirty-seven patients with IBD were studied (mean age 44 years, range 18-82
      years). Three patients had a history of thrombotic episodes. The 37 controls
      included 23 men and 17 women (mean age 48 years, range 16-89 years). Disease
      activity was assessed using the Harvey Bradshaw index for patients with Crohn's
      disease and the Truelove and Witts grading system for patients with ulcerative
      colitis. Levels of fibrinogen, antithrombin III (ATIII), protein C, protein S,
      activated protein C resistance (APCR), and the presence of a lupus anticoagulant
      (LA) were determined. Median ATIII levels in patients with IBD were significantly
      lower than controls (98% vs 106%, P = 0.007), while fibrinogen was elevated (4.2
      vs 3.3 g/liter, P = 0.026) despite quiescent disease activity. LA was detected in
      7/37 patients in the IBD group compared to 0/37 controls. (chi2 = 5.68, P =
      0.017). No significant difference was observed in levels of inherited
      thrombophilic factors and in particular APCR between IBD patients and controls.
      In conclusion, the presence of inherited thrombophilic defects, in particular
      APCR, is uncommon in patients with IBD and does not merit routine screening.

PMID- 9635630
TI  - Effect of leuprolide acetate in treatment of abdominal pain and nausea in
      premenopausal women with functional bowel disease: a double-blind, placebo
      controlled, randomized study.
AB  - We have previously reported impressive results in using a gonadotropin-releasing
      hormone analog, leuprolide acetate (Lupron), in the treatment of moderate to
      severe symptoms (especially abdominal pain and nausea) in patients with
      functional bowel disease (FBD). Pain is the hallmark of patients with FBD, and
      there is no consistent therapy for the treatment of these patients. The purpose
      of the present study was to expand the investigation to study similar patients
      (menstruating females) in a multicenter, double-blind, placebo-controlled,
      randomized study using Lupron Depot (which delivers a continuous dose of drug for
      one month), 3.75 mg (N = 32) or 7.5 mg (N = 33), or placebo (N = 35) given
      intramuscularly every four weeks for 16 weeks. Symptoms were assessed using daily
      diary cards to record abdominal pain, nausea, vomiting, early satiety, anorexia,
      bloating, and altered bowel habits. Additional assessment tools were quality of
      life questionnaires, psychological profile, oral-to-cecal transit using the
      hydrogen breath test, antroduodenal manometry, reproductive hormone levels, and
      global evaluations by both patient and investigator. Patients in both Lupron
      Depot-treated groups showed consistent improvement in symptoms; however, only the
      Lupron Depot 7.5 mg group showed a significant improvement for abdominal pain and
      nausea compared to placebo (P < 0.001). Patient quality of life assessments and
      global evaluations completed by both patient and investigators were highly
      significant compared to placebo (P < 0.001). All reproductive hormone levels
      significantly decreased for both Lupron Depot-treated groups by week 4 and were
      significantly different compared to placebo at week 16 (P < 0.001). This study
      shows that leuprolide acetate is effective in controlling the debilitating
      symptoms of abdominal pain and nausea in patients with FBD.

PMID- 9635632
TI  - Ischemic colitis, pulmonary embolism, and right atrial thrombosis in a patient
      with inherited resistance to activated protein C.

PMID- 9635633
TI  - Procalcitonin--marker, or mediator?

PMID- 9635634
TI  - Interpreting the venous-arterial PCO2 difference.

PMID- 9635635
TI  - Adding fuel to the fire--the supranormal oxygen delivery trials controversy.

PMID- 9635636
TI  - Outcome of septic shock: location, location, location.

PMID- 9635637
TI  - Accentuate the positive, don't eliminate the negative.

PMID- 9635638
TI  - Oxygen delivery: tusks versus flow.

PMID- 9635639
TI  - Bedside placement of enteral feeding tubes in the intensive care unit.

PMID- 9635640
TI  - Is there an answer to preventing unplanned extubations?

PMID- 9635641
TI  - On hemoglobin, hemorrhage, hypotension, and ... nitric oxide.

PMID- 9635642
TI  - Performance evaluations of mechanical ventilators: music to my ears.

PMID- 9635643
TI  - Understanding the enigma of hepatic failure.

PMID- 9635644
TI  - Mannitol: an old friend on the skids?

PMID- 9635645
TI  - Can gastric intramucosal pH measurement be useful in pediatric critical illness?

PMID- 9635646
TI  - Mortality is increased by procalcitonin and decreased by an antiserum reactive to
      procalcitonin in experimental sepsis.
AB  - OBJECTIVES: Procalcitonin (ProCT), the precursor to the calcitonin hormone, is
      abnormally increased in experimental and clinical systemic inflammation,
      including sepsis. Initially, we investigated the effects of supraphysiologic
      amounts of ProCT administered to animals with septic peritonitis. Subsequently,
      we evaluated the efficacy of prophylactic and therapeutic immune blockade of
      ProCT in this lethal model of sepsis. DESIGN: Prospective, experimental,
      controlled study. SETTING: Animal research laboratory approved by the American
      Association for the Accreditation of Laboratory Animal Care at a Veterans Affairs
      Medical Center. SUBJECTS: Young male Golden Syrian hamsters, weighing 90 to 120
      g. INTERVENTIONS: In the first study, serum ProCT concentrations were measured in
      animals at 0, 3, 6, 12, and 24 hrs after induction of sepsis by intraperitoneal
      implantation of pellets containing Escherichia coli (5 x 10(8) colony-forming
      units/pellet). In the second study, with mortality as the end point, 30 microg/kg
      of isolated, purified human ProCT in 10% hamster serum (experimental) or an equal
      volume of 10% hamster serum (control) were administered intravenously at the time
      of the E. coli peritoneal implantation. In the third study, experimental animals
      received intraperitoneal injections of a multiregion-specific goat antiserum
      reactive to hamster ProCT 1 hr before and 24 hrs after E. coli implantation,
      while control animals received nonimmune goat serum at the same time points. In
      the final study, the same antiserum was administered in five divided doses during
      the 24 hrs after the insertion of E. coli. MEASUREMENTS AND MAIN RESULTS: In the
      initial study, ProCT concentrations were increased shortly after induction of
      sepsis and peaked at 12 hrs. Administration of exogenous ProCT to septic animals
      significantly increased mortality compared with control animals (93% vs. 43%,
      p=.02). Prophylactic blockade of ProCT almost completely protected the animals
      from the lethal effects of sepsis: the 102-hr mortality rate in the experimental
      group was 6% compared with 62% in the control group (p < .003). In the
      therapeutic trial, the 102-hr mortality rate was 54% in experimental animals
      compared with 82% in control animals (p < .045). CONCLUSIONS: These results
      demonstrate that increased ProCT exacerbates mortality in experimental sepsis,
      whereas neutralization of ProCT increases survival. Thus, ProCT, in addition to
      being an important marker of severity of systemic inflammation and mortality, is
      an integral part of the inflammatory process and directly affects the outcome.

PMID- 9635647
TI  - Value of the venous-arterial PCO2 gradient to reflect the oxygen supply to demand
      in humans: effects of dobutamine.
AB  - OBJECTIVE: To test the value of venous-arterial PCO2 gradient (deltaPCO2)
      measurements to reflect the adequacy of cardiac index (CI) to oxygen demand in
      patients submitted to rapid changes of CI and oxygen demand. DESIGN: Prospective,
      comparative study. SETTING: Medical intensive care unit of a university hospital.
      PATIENTS: Ten patients with congestive heart failure exhibiting low baseline CI
      (< or =2.5 L/min/m2) but no evidence of global tissue hypoxia, as attested by the
      absence of clinical signs of shock and by normal blood lactate concentrations.
      INTERVENTIONS: Infusion of incremental doses of dobutamine: 0 (D0), 5 (D5), 10
      (D10), and 15 (D15) microg/kg/min. MEASUREMENTS AND MAIN RESULTS: The CI
      increased by a linear fashion from D0 (1.6+/-0.1 L/min/m2) to D15 (2.4+/-0.2
      L/min/m2) (p< .05). The mixed venous oxygen saturation (SVO2) increased from D0
      (49+/-2%) to D10 (61+/-2%) (p < .05) and remained unchanged from D10 to D15 (60+/
      2%). The oxygen extraction ratio (O2 ER) and the deltaPCO2 decreased from D0
      (48+/-2% and 9+/-1 torr [1.2+/-0.3 kPa], respectively) to D10 (36+/-2% and 5+/-1
      torr [0.7+/-0.1 kPa], respectively) (p < .05 for both comparisons) and remained
      unchanged from D10 to D15 (36+/-2% and 6+/-1 torr [0.8+/-0.1 kPa], respectively).
      The biphasic courses of SVO2, O2 ER, and deltaPCO2 were related to the course of
      oxygen consumption that remained constant from D0 (113+/-9 mL/min/m2) to D10
      (112+/-8 mL/min/m2) and significantly increased from D10 to D15 (127+/-10
      mL/min/m2) (p <.05). CONCLUSIONS: deltaPCO2 can be reliably used at the bedside
      for informing on the adequacy of CI with respect to a given metabolic condition,
      and particularly for detecting changes in oxygen demand (e.g., the changes
      accompanying drug-induced changes in CI). In this regard, deltaPCO2, together
      with O2 ER and SVO2, can help to assess the adequacy of CI to global oxygen
      demand.

PMID- 9635648
TI  - Relationship of mortality to increasing oxygen delivery in patients > or = 50
      years of age: a prospective, randomized trial.
AB  - OBJECTIVE: To investigate the relationship of mortality to early resuscitation
      using two levels of oxygen delivery (DO2) in critically ill surgical patients >
      or =50 yrs of age who were stratified into groups: age < or =75 yrs (age 50 to 75
      yrs group); and age >75 yrs (age >75 yrs group). DESIGN: A prospective,
      randomized trial, continued from a previous project. SETTING: Surgical intensive
      care unit, university affiliated. PATIENTS: Consecutive patients, >50 yrs of age,
      unable to generate a DO2 of > or =600 mL/min/m2 with fluid resuscitation alone,
      with a diagnosis of systemic inflammatory response syndrome, sepsis, severe
      sepsis, septic shock, and/or acute respiratory distress syndrome. INTERVENTIONS:
      During the first 24 hrs of resuscitation, patients were randomized to receive
      fluids, blood transfusions, and vasoactive agents in order to achieve DO2
      treatment goals of > or =600 mL/ min/m2 in the protocol group and 450 to 550
      mL/min/m2 in the control group. MEASUREMENTS AND MAIN RESULTS: One hundred five
      patients completed the study. In patients aged 50 to 75 yrs, the mortality rate
      was 21% (9/43) in the protocol group and 52% (12/23) in the control group (p=.01,
      95% confidence interval of -58% to -4%). In patients >75 yrs of age, the
      mortality rate was 57% (12/21) in the protocol group and 61% (11/18) in the
      control group. Oxygen extraction ratios (O2ER) and oxygen consumption values were
      significantly (p=.02) lower in the age >75 yrs group compared with the age 50 to
      75 yrs group. CONCLUSIONS: Patients 50 to 75 yrs of age receiving a DO2 of > or
      =600 mL/min/m2 demonstrated a statistically significant (p=.01) improved survival
      rate over patients in the control group. Patients >75 yrs of age demonstrated no
      benefit from attempts to increase DO2 to >600 mL/min/m2, and they may have been
      overtreated as reflected by the lower O2ER values in this age group. Treating to
      an O2ER that reflects a balance between oxygen consumption and DO2 may be an
      alternative goal that allows individual titration.

PMID- 9635649
TI  - Septic shock: an analysis of outcomes for patients with onset on hospital wards
      versus intensive care units.
AB  - OBJECTIVE: To determine if early interventions for septic shock were associated
      with reduced mortality. DESIGN: Retrospective cohort study. SETTING: University
      hospital intensive care unit (ICU) and general wards. PATIENTS: Forty-one
      consecutive patients prospectively identified with positive blood cultures and
      septic shock. Although all patients were eventually treated in an ICU, ten (24%)
      patients were on a general ward at the onset of septic shock, and 31 (76%) were
      in an ICU setting. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Over a
      period of 9 mos, a cohort of 41 patients who had positive blood cultures and
      septic shock was prospectively identified. The 28-day crude mortality was 46% (19
      deaths). We compared the management of septic shock and outcome for patients on a
      general ward vs. those patients in an ICU setting. Of the ten patients on the
      ward at time of shock onset (median age 55.5 yrs; median Acute Physiology and
      Chronic Health Evaluation [APACHE] II score of 18.5), seven (70%) died. In
      contrast, the 31 patients receiving intensive care when shock developed were
      older and more ill (median age 66 yrs; median APACHE II 24), yet had a mortality
      of 39% (12 deaths). The odds ratio (OR) for death for ward patients compared with
      ICU patients was 3.57 (p=.17). In a multivariate logistic regression analysis,
      two risk factors for mortality were important: APACHE II score (p=.015) and ward
      status (p=.08). Candida species in the bloodstream is known to have a high
      attributable mortality. When type of bloodstream pathogen (Candida species vs.
      bacteria) was added to the model, APACHE II (OR 2.64 for 10-unit increase)
      remained significant (p=.014), but ward status (OR 3.97) became statistically
      nonsignificant (p=.222). The patients who were on a general ward when their shock
      developed had a median delay of 67 mins before transfer to an ICU setting. Ward
      patients received an intravenous fluid bolus after a median delay of 27 mins,
      whereas those in the ICU who received a fluid bolus did so after a median of 15
      mins (p=.48). Ward patients also had a median delay of 310 mins to receive
      inotropic support compared with a median 22.5 mins (p=.037) for the patients in
      an ICU setting when shock started. CONCLUSIONS: The data suggest that for
      patients with septic shock on wards, there were clinically important delays in
      transfer of patients to the ICU, receipt of intravenous fluid boluses, and
      receipt of inotropic agents. However, the most powerful predictors of mortality
      were APACHE II scores and bloodstream infection with Candida species.

PMID- 9635650
TI  - Effects of continuous negative extrathoracic pressure versus positive end
      expiratory pressure in acute lung injury patients.
AB  - OBJECTIVE: To compare the effects of continuous negative extrathoracic pressure
      (CNEP) and positive end-expiratory pressure (PEEP) at the same level of
      transpulmonary pressure. DESIGN: Prospective analysis. SETTING: Medical intensive
      care unit of a university hospital. PATIENTS: Nine consecutive acute lung injury
      patients. Patients with cardiac failure and patients with chronic lung disease
      were excluded from the investigation. INTERVENTIONS: The patients were sedated
      and paralyzed while receiving mechanical ventilation and were studied in three
      different conditions: a) using a PEEP of 0 cm H2O (zero end-expiratory pressure);
      b) using a PEEP of 15 cm H2O; c) using CNEP. CNEP was applied to the thorax and
      the upper abdomen and its level was chosen to obtain a transpulmonary pressure
      similar to the one observed at a PEEP of 15 cm H2O. All patients had an arterial
      catheter, a pulmonary artery catheter, and a thermistor-tip fiberoptic catheter
      for thermo-dye-dilution in the femoral artery. These catheters were connected to
      an integrated monitoring system. We also placed an esophageal catheter in each
      patient to detect esophageal pressure. MEASUREMENTS AND MAIN RESULTS: For each
      step, we assessed the hemodynamic variations by measuring intravascular pressures
      (via a pulmonary artery catheter), transmural pressures (computed by subtracting
      esophageal pressure from intravascular pressure), and blood volumes (derived from
      the technique of double indicator). The application of CNEP of -20+/-0.7 cm H2O
      produced a venous admixture and PaO2/FO2 improvement similar to that obtained
      with a PEEP of 15 cm H2O. This procedure is associated with a higher cardiac
      index (5.5+/-1.5 vs. 4.6+/-1.2 L/min/m2; p < .05) coupled with lower central
      venous pressure, pulmonary artery occlusion pressure, and higher transmural
      pressures and blood volume parameters. CONCLUSIONS: In acute lung injury
      patients, a CNEP of -20 cm H2O has the capability to obtain transpulmonary
      pressure and lung function improvement similar to a PEEP of 15 cm H2O. CNEP
      differs from the positive pressure by increasing the venous return and the
      preload of the heart, and has no negative effects on cardiac performance.

PMID- 9635651
TI  - Delivery of high concentrations of inspired oxygen via Tusk mask.
AB  - OBJECTIVES: Nonrebreather face masks (NRM) are frequently used in patients with
      respiratory distress and profound hypoxemia. A simpler modification to the
      partial rebreather face mask, using only two pieces of respiratory tubing or
      "tusks," has also been shown to increase FiO2 compared with the NRM in five
      normal subjects. Clinically, we have observed this modification to further
      increase PaO2 in critically ill patients already using the NRM in the intensive
      care unit. This study was designed to compare the Tusk mask with the NRM in both
      a larger group of normal subjects and in patients with underlying lung disease.
      DESIGN: Prospective, randomized, crossover study. SETTING: A university teaching
      hospital and tertiary care referral center. SUBJECTS: Sixteen normal subjects (11
      male and 5 female; age 30.4+/-6.8 [SD] yrs) and seven patients with interstitial
      lung disease (ILD) (3 male and 4 female; age 68.1+/-11.9 yrs). INTERVENTIONS:
      Subjects and patients served as their own controls and were randomized to wear
      either the NRM or Tusk mask for a 30-min period. After a 60-min washout period,
      the other mask was applied. MEASUREMENTS AND MAIN RESULTS: Arterial blood gas
      measurements were performed immediately before and at the end of each 30-min test
      period. Respiratory synchronization during the study period was achieved, using a
      metronome. In the normal subjects, PaO2 using the NRM and Tusk masks increased
      290.0+/-57.1 torr (38.6+/-7.6 kPa) and 330.0+/-68.9 torr (44.0 +/-9.2 kPa),
      respectively (p=.032). PaO2 increased 293.4+/-38.0 torr (39.1+/-5.1 kPa) with the
      NRM and 378.4+/-61.7 torr (50.4+/-8.2 kPa) with the tusk mask (p=.001) in the
      patients with ILD. There was no statistically significant change seen in mean
      PaCO2 with either mask in either group. The mean PaO2 returned to within 6% of
      baseline in both groups after the washout period. CONCLUSIONS: Both normal
      subjects and patients with compromised pulmonary function achieved a higher PaO2
      using a Tusk mask than when using the conventional NRM, at the same oxygen flow
      rate. Patients with hypoxemia may obtain lifesaving benefit from the additional
      concentration of oxygen delivered via the Tusk mask.

PMID- 9635652
TI  - Air insufflation technique of enteral tube insertion: a randomized, controlled
      trial.
AB  - OBJECTIVE: To test air insufflation as an adjunct to placement of enteral feeding
      tubes. DESIGN: Prospective, randomized study. SETTING: Intensive care unit in a
      tertiary hospital. SUBJECTS: Sixty-four consecutive patients requiring enteral
      nutrition, in whom a decision to insert a nasoenteral feeding tube was made.
      INTERVENTIONS: A 12-Fr feeding tube was inserted to the level of the fundus of
      the stomach. A 60-mL syringe was used to pump 500 mL of air into the stomach. The
      tube was then advanced. An abdominal flat plate was obtained within 2 hrs of
      completion of the procedure and the tube position noted. If the tube was not in
      the duodenum, the patient was placed on a promotility agent and a repeat
      radiograph was performed the next day. The technique varied from our control
      technique only by the instillation of air. MEASUREMENTS AND MAIN RESULTS: Using
      the study technique, 21 of 32 tubes were successfully placed, as seen on the
      initial radiograph, in our study patients compared with only 12 of 34 tubes in
      our control patients (p< .02). In addition, the success rate at 24 hrs was 25 of
      32 vs. 16 of 34 (p< .02). Only 3 of 21 tubes placed in the antrum, body, or
      fundus of the stomach advanced to the duodenum the following day, compared with 5
      of 12 tubes initially placed in the pylorus (p< .075). No complications were
      noted. CONCLUSION: Instilling air into the stomach may facilitate the ability to
      get the feeding tube to the level of the pylorus, at which point it is more
      likely to advance into the duodenum and beyond.

PMID- 9635653
TI  - White blood cell counts and plasma C3a have synergistic predictive value in
      patients at risk for acute respiratory distress syndrome.
AB  - OBJECTIVE: To investigate and select nonassociated variables with predictive
      value for acute respiratory distress syndrome (ARDS) in patients at risk. DESIGN:
      Prospective, observational study. SETTING: A university hospital intensive care
      unit. PATIENTS: Twenty-four critically ill patients with different risk factors
      for ARDS. INTERVENTIONS: Arterial and mixed venous blood, as well as urine
      samples, were collected. Invasive hemodynamic measurements were performed.
      MEASUREMENTS AND MAIN RESULTS: Fifty-nine variables pertaining to the
      cardiorespiratory, hepatic, immunologic, and renal systems and including plasma
      complement activation products C3a and SC5b-9 and polymorphonuclear elastase,
      were determined every 6 hrs for 3 days in patients at risk for ARDS. Associations
      among variables were investigated and the predictive value of nonassociated
      variables for ARDS was determined. Patients who developed ARDS (n=8) had lower
      white blood cell counts at the time they entered the study (p=.006) and during
      the first 24 hrs thereafter (p=.032). Also, plasma C3a concentrations were
      markedly higher during the first 24 hrs in patients who developed ARDS (p=.006).
      Plasma C3a had better predictive value than did white blood cell counts for
      cutoff points set by discriminant analysis at 1075 ng/mL (1.075 x 10(-3) g/L) and
      5700 cells/mL, respectively. The combination of both variables in a discriminant
      function improved the predictive value for ARDS. CONCLUSIONS: The most notable
      and nonassociated alterations observed in patients who developed ARDS were lower
      white blood cell counts and higher plasma C3a concentrations compared with counts
      and concentrations in patients who did not develop ARDS. Plasma C3a
      concentrations showed better predictive value than white blood cell counts. The
      combination of white blood cell counts with plasma C3a concentrations
      synergistically improved the predictive value for ARDS. This combination may
      prove useful for identifying subpopulations at highest risk for ARDS and may
      contribute to make treatment at an early stage of the syndrome possible.

PMID- 9635654
TI  - Unplanned extubation: risk factors of development and predictive criteria for
      reintubation.
AB  - OBJECTIVES: To define patients at risk for unplanned extubation; to assess the
      influence of nursing workload on the incidence of unplanned extubation; and to
      determine predictive criteria for patients requiring reintubation. DESIGN: A
      prospective, case-control study, with 10 and 15 mos of data collection. SETTING:
      University medical intensive care department. PATIENTS: In the first study, which
      lasted 10 mos, unplanned extubation occurred in 40 (14%) of 281 ventilated and
      intubated patients; 36 cases were sufficiently documented to be compared with 74
      intubated and ventilated controls. In the second study, which lasted 15 mos, the
      reintubated patients (n=23) of a series of 62 unplanned extubation patients were
      compared with those who were not reintubated (n=39). INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: The following parameters were recorded: gender,
      age, main reason for admission, Simplified Acute Physiology Score II, route of
      intubation (oral or nasotracheal), tube diameter, ventilatory mode, FiO2,
      frequency and tidal volume delivered by the ventilator immediately before
      unplanned extubation, arterial blood gases performed 24 hrs before unplanned
      extubation, the presence of any sedation with, in this case, the last Ramsay
      score, the presence of hand restraints, the presence of weaning of ventilation,
      the accidental or deliberate nature of unplanned extubation, the Glasgow Coma
      Score at the time of unplanned extubation, the duration of ventilation before
      unplanned extubation, total duration of ventilation and stay in the intensive
      care unit, and the patient's survival or death. The nursing workload was
      evaluated using a score derived from the Projet de Recherche en Nursing and
      adapted to intensive care. Unplanned extubation patients were more frequently
      intubated orally than controls (33.3% vs. 14.9%, respectively; p< .05). In the
      population of sedated patients, unplanned extubation patients were more
      frequently agitated than controls (60% vs. 19%, respectively; p < .05). The
      nursing workload did not differ between days with and days without unplanned
      extubation. Twenty-three (37%) of the 62 cases of documented unplanned extubation
      were reintubated. Predictive factors of reintubation are, in decreasing order of
      importance: Glasgow Coma Score of <11, accidental nature of unplanned extubation,
      and a PaO2/FiO2 ratio <200 torr (<26.7 kPa). CONCLUSIONS: Patients at risk for
      unplanned extubation are characterized by oral intubation and insufficient
      sedation. In the department studied, and with the specific score used, we did not
      observe a relationship between the nursing workload and the incidence of
      unplanned extubation. A Glasgow Coma Score of <11, the accidental nature of
      unplanned extubation, and a PaO2/FiO2 ratio <200 torr (<26.7 kPa) are factors
      associated with a risk of reintubation.

PMID- 9635655
TI  - A rapid assay for the detection of circulating D-dimer is associated with
      clinical outcomes among critically ill patients.
AB  - OBJECTIVE: To determine whether the results of a rapid, semiquantitative assay
      for the detection of circulating D-dimer in whole blood (SRDD assay) are
      associated with the occurrence of clinical outcomes among critically ill
      patients. DESIGN: Prospective, blinded, single-center study. SETTING: Medical
      intensive care unit (ICU) of Barnes-Jewish Hospital, St. Louis, MO, a university
      affiliated teaching hospital. PATIENTS: Three hundred twenty-three adult patients
      admitted to a medical ICU. INTERVENTIONS: Collection of blood samples within 24
      hrs of ICU admission. MEASUREMENTS AND MAIN RESULTS: The main outcome measures
      evaluated included vascular thrombosis, hospital mortality, and the development
      of multiorgan dysfunction. Fifty (15.5%) patients were found to have increased
      concentrations of D-dimer as detected by the SRDD assay within 24 hrs of ICU
      admission. The concentrations of plasma D-dimer simultaneously measured by an
      enzyme immunoassay based on the same antibody were significantly greater among
      patients with a positive SRDD assay compared with patients with a negative SRDD
      assay (1214+/-483 vs. 405+/-407 ng/mL; p< .001). The hospital mortality rate was
      significantly greater among SRDD-positive patients compared with SRDD-negative
      patients (32.0% vs. 15.0%; p=.004). SRDD-positive patients also had significantly
      greater frequencies of acquired multiorgan dysfunction (48.0% vs. 17.6%; p <
      .001), severe sepsis or septic shock (56.0% vs. 20.9%; p< .001), and vascular
      thrombosis (14.0% vs. 4.0%; p=.005) compared with SRDD-negative patients.
      Multiple logistic regression analysis identified the presence of increased
      concentrations of D-dimer, detected by a positive SRDD assay, as being
      independently associated with vascular thrombosis (adjusted odds ratio 5.06; 95%
      confidence interval 2.96 to 8.65; p=.003) and the development of multiorgan
      dysfunction (adjusted odds ratio 1.51; 95% confidence interval 1.28 to 1.78;
      p=.012). CONCLUSIONS: Our preliminary investigation suggests that the results
      from a rapid whole blood assay for the semiquantitative detection of circulating
      D-dimer are associated with clinical outcomes among patients admitted to a
      medical ICU. In addition, the use of D-dimer to identify the presence of active
      intravascular thrombosis may identify patients likely to benefit from
      antithrombotic therapies in the ICU setting.

PMID- 9635656
TI  - Clinical death and the measurement of stressed vascular volume.
AB  - OBJECTIVES: To measure stressed vascular volume in humans and to review the
      concepts of stressed and unstressed vascular volume. DESIGN: Observational study
      during surgical procedure. SETTING: Operating room at a university hospital.
      PATIENTS: Five patients undergoing hypothermic circulatory arrest for surgery on
      major vessels. INTERVENTION: We measured the volume that drained from the patient
      to the reservoir of the pump when the pump was turned off. MEASUREMENTS AND MAIN
      RESULTS: Stressed volume was 20.2+/-1.0 mL/kg, which is 30% of the predicted
      blood volume of these patients. CONCLUSION: The amount of blood volume that
      determines vascular filling pressure is only about a quarter of the total
      predicted volume, which means that there is a large reserve of unstressed volume
      that can be recruited to maintain vascular filling pressure.

PMID- 9635657
TI  - Bedside determination of fluid accumulation after cardiac surgery using segmental
      bioelectrical impedance.
AB  - OBJECTIVES: Bioelectrical impedance analysis (BIA) is based on the physical
      property of tissues to conduct electrical currents, impedance being inversely
      related to tissue fluid content. At high frequency, the electrical current flows
      across both intracellular and extracellular pathways, making the assessment of
      fat-free mass possible while a low-frequency current flows through the
      extracellular space. Similarly, segmental BIA may be used to assess segmental
      body fluid repartition. The aim of this study was to assess fluid accumulation
      after cardiac surgery by multiple frequency segmental BIA. DESIGN: Observational,
      clinical study. SETTING: A 17-bed, surgical intensive care unit in a university
      hospital. PATIENTS: Twenty-six patients before and after open-heart surgery with
      cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After
      surgery, fluid accumulation resulted in a decrease in whole-body and segmental
      bioelectrical impedance in the arm and in the trunk. There was a good correlation
      between the fluid accumulation measured by fluid balance and by whole-body or
      segmental impedance changes. The major part (71%) of fluid accumulation occurred
      in the trunk. Multiple frequency measurements did not indicate a fluid shift
      between the intra- and extracellular compartments. CONCLUSION: Cardiac surgery
      produced a significant decrease in segmental trunk BIA, reflecting fluid
      accumulation at the trunk level.

PMID- 9635658
TI  - Resuscitation after hemorrhage using recombinant human hemoglobin (rHb1.1) in
      rats: effects on nitric oxide and prostanoid systems.
AB  - OBJECTIVES: Hemoglobin-based oxygen carriers are designed to replace blood volume
      and to increase oxygen delivery to tissues after blood loss. The goals of the
      present study were two-fold: a) to determine the systemic and regional vascular
      effects of resuscitation with recombinant human hemoglobin (rHb1.1) in rats
      during controlled hemorrhage; and b) to determine whether nitric oxide (NO) or
      prostaglandins were involved in the observed responses. DESIGN: Paralyzed,
      ventilated rats were hemorrhaged (18 mL blood/kg body weight) during halothane
      anesthesia and allowed to stabilize for 30 mins. Systemic and regional
      hemodynamics and oxygen delivery were monitored at three time points, using the
      radioactive microsphere method. Microspheres were first infused at the end of the
      hemorrhage stabilization period (t=0 min). rHb1.1 (1 g/kg body weight) or rHb1.1
      diluent (phosphate buffered saline, 36 mL/kg body weight) were infused over 20
      mins and microspheres were administered again, 30 mins later (t=50 mins). Saline
      (0.5 mL), indomethacin (5 mg/kg to inhibit cyclooxygenase), or NG-monomethyl-L
      arginine (L-NMMA, 100 mg/kg, to inhibit NO synthase) were then infused in rHb1.1
      treated rats and microspheres injected once more (t=80 mins). SETTING: Research
      laboratory. SUBJECTS: Male Wistar rats (n=37). INTERVENTIONS: Recombinant human
      hemoglobin (rHb1.1), rHb1.1 diluent (phosphate buffered saline) resuscitation of
      hemorrhaged rats. Saline, L-NMMA, or indomethacin treatment after resuscitation.
      MEASUREMENTS AND MAIN RESULTS: Resuscitation with rHb1.1 increased mean arterial
      pressure (MAP), cardiac output, and systemic oxygen delivery significantly when
      compared with diluent. After rHb1.1 resuscitation, regional blood flows were
      significantly increased in skin, kidney, spleen, and heart compared with diluent
      resuscitation. Compared with saline treatment after rHb1.1 resuscitation, L-NMMA
      increased MAP and regional resistances in virtually all tissues; indomethacin did
      not alter MAP, but increased resistance in the brain. CONCLUSIONS: These data
      indicate that rHb1.1 resuscitation was more effective than diluent in improving
      systemic and regional hemodynamics and oxygen delivery, suggesting that rHb1.1
      may be of benefit in the treatment of acute blood loss. Increased resistance
      after L-NMMA in the presence of rHb1.1 indicated that rHb1.1 resuscitation did
      not eliminate NO dependent circulatory control. Increased resistance after
      indomethacin in brain indicated that vasodilator prostanoids were important in
      regulating vascular resistance in these tissues after rHb1.1 resuscitation.

PMID- 9635659
TI  - Mechanical performance of clinically available, neonatal, high-frequency,
      oscillatory-type ventilators.
AB  - OBJECTIVE: To perform a functional evaluation of five different high-frequency,
      oscillatory-type ventilators that are currently being marketed for neonatal high
      frequency oscillation. DESIGN: Observational animal study. SETTING: Laboratory.
      SUBJECTS: New Zealand White male rabbits. INTERVENTIONS: Oscillator waveforms and
      delivered volumes were measured plethysmographically for the following
      ventilators: the SensorMedics 3100 A; the Drager Baby Log 8000; the Metran
      Humming V; the Infant Star; and the Infant Star 950. The independent variables
      which were adjusted included frequency (5 to 15 Hz), amplitude (25% to 100%),
      mean airway pressure (5 to 25 cm H2O) and lung injury. MEASUREMENTS AND MAIN
      RESULTS: At 15 Hz, the volume delivered at the 100% amplitude setting varied from
      2.1 to 8.8 mL. Generally, the delivered volume decreased with increasing
      frequency, and with increased percentage of amplitude. Volume delivery was
      relatively unaffected by mean airway pressure but decreased with lung injury.
      Waveforms ranged from pure sinusoidal to a complex square wave. The handling of
      inspiration/expiration time ratios was ventilator specific. The SensorMedics
      inspiration/ expiration ratio is user selected over a range from 1:2.3 (30%
      inspiratory time) to 1:1 (50% inspiratory time) and once selected it is
      consistent over its entire range of operating frequencies. The Drager ratio is
      machine determined and varied from 1:2.5 at 5 Hz to 1:1 at 15 Hz. Inspiratory
      time of the Infant Star is machine set at 18 msecs such that the
      inspiration/expiration ratio is 1:10.1 at 5 Hz and 1:2.7 at 15 Hz. The Humming V
      has a fixed inspiration/expiration ratio of 1:1. The relationship of the mean
      airway pressure displayed on the ventilator to the alveolar occlusion pressure
      varied considerably among devices. The displayed mean pressure could either
      overestimate (SensorMedics at 33% inspiratory time or Infant Star), approximate
      (Humming V), or underestimate (Drager) the mean lung distending pressure measured
      during a brief occlusion maneuver. CONCLUSIONS: The findings demonstrate large
      variations in machine performance. The ventilators also differed profoundly in
      complexity of operation and versatility as neonatal ventilators.

PMID- 9635660
TI  - Hypoxia-reoxygenation is as damaging as ischemia-reperfusion in the rat liver.
AB  - OBJECTIVE: We hypothesized that the extent of injury and release of xanthine
      oxidase, an oxidant generator, into the circulation would be less in normal-flow
      hypoxia-reoxygenation than in equal duration no-flow ischemia-reperfusion.
      DESIGN: Randomized study. SETTING: University-based animal research facility.
      SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: The livers were isolated,
      perfused, and then randomly subjected to 2 hrs of hypoxia (normal flow, low
      oxygen) or ischemia (no flow, no oxygen), and 2 hrs of reperfusion. Hepatocytes
      were also isolated, and were subjected to either: a) hypoxia (0, 2, 4, and 6
      hrs); or b) hypoxia (2 and 4 hrs) with reoxygenation (2 hrs). MEASUREMENTS AND
      MAIN RESULTS: The extent of liver injury (as assessed by release of
      hepatocellular enzymes) and the release of xanthine oxidase were measured from
      isolated-perfused rat livers and cultured hepatocytes. The pattern of release of
      xanthine oxidase in isolated-perfused liver effluent was different in hypoxia
      reoxygenation compared with ischemia-reperfusion. During hypoxia, xanthine
      oxidase gradually increased in the effluent; then, the xanthine oxidase decreased
      to low concentrations during reoxygenation. After ischemia, there was a sharp
      spike in xanthine oxidase at 1 min of reperfusion, with a rapid decrease to low
      concentrations. The total release of xanthine oxidase during hypoxia
      reoxygenation was similar to that during ischemia-reperfusion. Lactate
      dehydrogenase and other markers of liver injury showed a pattern of release that
      was similar to that of xanthine oxidase, but the total release of markers was not
      different between the two groups. In hepatocytes, most of the release of enzymes
      occurred in hypoxia, and the rate of release was not different between hypoxia
      and hypoxia-reoxygenation. CONCLUSIONS: Hypoxia-reoxygenation results in as much
      damage to the liver as ischemia-reperfusion, and results in the release of a
      similar amount of oxidant-producing xanthine oxidase into the circulation.

PMID- 9635661
TI  - Extracorporeal heparin adsorption following cardiopulmonary bypass with a heparin
      removal device--an alternative to protamine.
AB  - OBJECTIVES: To evaluate the therapeutic efficacy and applicability of a heparin
      removal device (HRD) based on plasma separation and poly-L-lysine (PLL) affinity
      adsorption as an alternative to protamine in reversing systemic heparinization
      following cardiopulmonary bypass (CPB). DESIGN: A prospective study. SETTING:
      University research laboratory. SUBJECTS: Adult female swine (n=7).
      INTERVENTIONS: Female Yorkshire swine (n=7, 67.3+/-3.5 [SEM] kg) were subjected
      to 60 mins of right atrium-to-aortic, hypothermic (28 degrees C) CPB. After
      weaning from CPB, the right atrium was recannulated with a two-stage, dual-lumen
      cannula which was connected to an HRD via extracorporeal circulation. Blood flow
      was drained at 1431.2+/-25.4 mL/min from the inferior vena cava, through the
      plasma separation chamber of the HRD (where heparin was bound to PLL), and
      reinfused into the right atrium. The HRD run time was determined by a previously
      established mathematical model of first-order exponential depletion. MEASUREMENTS
      AND MAIN RESULTS: Heart rate, mean arterial pressure, pulmonary arterial
      pressure, central venous pressure, kaolin and celite activated clotting time
      (ACT), activated partial thromboplastin time (APTT), heparin concentration, and
      plasma free hemoglobin were obtained before, during, and after the use of the
      HRD. Pre-CPB ACT was 167+/-89 secs (kaolin) and 99+/-7 secs (celite), and APTT
      was 34+/-5 secs. The HRD run time averaged 27.4 +/-1.5 mins targeted to remove
      90% total body heparin. Use of the HRD was not associated with any adverse
      hemodynamic reactions or increases in plasma free hemoglobin. The heparin
      concentration immediately following CPB was 4.85+/-0.24 units/mL, with ACT >1000
      secs and APTT >150 secs in all animals. During heparin removal, total body
      heparin content followed first-order exponential depletion kinetics. At the end
      of the HRD run, heparin concentration decreased to 0.51+/-0.09 units/mL, with
      kaolin ACT returning to 177+/-22 secs, celite ACT returning to 179+/-17 secs, and
      APTT returning to 27+/-3 secs (p > .05 vs. pre-CPB baseline for all variables).
      CONCLUSIONS: The HRD is capable of reversal of anticoagulation following CPB
      without significant blood cell damage or changes in hemodynamics. The HRD,
      therefore, can serve as an alternative to achieve heparin clearance in clinical
      situations where use of protamine may be contraindicated.

PMID- 9635662
TI  - Efficacy of inhaled prostanoids in experimental pulmonary hypertension.
AB  - OBJECTIVES: To evaluate the effects of inhaled prostacyclin (PGI2) and inhaled as
      well as intravenous prostaglandin E1 (PGE1) on thromboxane A2 mimetic-induced
      pulmonary vasoconstriction. Active pulmonary vasoconstriction was to be
      distinguished from passive resistance to blood flow. DESIGN: Prospective,
      randomized, crossover study. SETTING: Experimental animal laboratory. SUBJECTS:
      Eight anesthetized and paralyzed sheep. INTERVENTIONS: The stable thromboxane A2
      mimetic, U46619, was infused in increasing dosage to obtain a stable pulmonary
      hypertension of approximately 30 mm Hg. Subsequently, PGE1 aerosol (0.6, 6, 58,
      259 ng/kg/min), intravenous PGE, (0.5 microg/kg/min), or PGI2 aerosol (27
      ng/kg/min) were administered in randomized order. MEASUREMENTS AND MAIN RESULTS:
      Active pulmonary vasoconstriction was assessed by determining the pulmonary
      pressure-flow relationship (PPFR). For measurement of pulmonary artery flow, an
      ultrasound flow probe was placed around the pulmonary artery after a sternotomy.
      Pulmonary arterial pressure was measured with a pulmonary artery flotation
      catheter. Flow was varied by partial occlusion of the inferior vena cava or
      incremental opening of an arterio-venous fistula between the large neck vessels.
      The primary end points were the slope of the resulting linear pressure-flow
      relationship, and pulmonary vascular resistance (PVR). Infusion of U46619
      increased the slope of the PPFR (2.9+/-0.7 vs. 4.2+/-1.2 mm Hg/L/min [median+/
      semi-interquartile range]; p < or = .05), and PVR (221+/-20 vs. 424+/-57 dyne x
      sec/cm5) (p < .05). Neither dose of PGE1 aerosol induced changes of the slope of
      PPFR or PVR. In contrast, intravenous administration of the same drug reduced the
      slope of the PPFR (4.0+/-1.0 vs. 3.1+/-0.4) (p < .05) but left PVR unchanged.
      Inhalation of PGI2 reduced both the slope of the PPFR, slightly but
      significantly, and PVR (424+/-98 vs. 323+/-26 dyne x sec/cm5) (p < .05).
      CONCLUSIONS: This study is the first to show reduction of active pulmonary
      vasoconstriction by PGI2 aerosol. Neither inhalation nor intravenous
      administration of PGE1 reduced PVR but the latter reduced the slope of PPFR. We
      conclude that PGE1 has potential for pulmonary vasodilation, but that it is
      ineffective as an aerosol, even in high doses, in sheep. PVR may fail to reflect
      drug-induced pulmonary vasodilation.

PMID- 9635663
TI  - Gut intramucosal pH as an early indicator of effectiveness of therapy for
      hemorrhagic shock.
AB  - OBJECTIVE: To determine the value of intramucosal pH for evaluating the
      effectiveness of treatment for hemorrhagic shock. DESIGN: Randomized, controlled
      trial. SETTING: University center, animal laboratory. SUBJECTS: Eighteen piglets,
      weighing 17 to 23 kg. INTERVENTIONS: Anesthetized animals were bled to a mean
      arterial pressure (MAP) of 40 to 50 mm Hg and a 70% reduction in cardiac output
      during a 1-hr period. This state was maintained for the next hour. The piglets
      were treated with crystalloid solution to restore cardiac output and MAP during
      the subsequent 80 mins of the experiment. Some animals were given vasoactive
      drugs during volume therapy to modulate splanchnic perfusion and increase the
      diversity of values of various variables. MEASUREMENTS AND MAIN RESULTS: Systemic
      hemodynamic and oxygen transport variables were monitored. Tissue oxygen tensions
      were measured in the liver and abdominal subcutaneous tissue layer. Gut
      intramucosal pH (pHi) was determined, using a balloon tonometer. The animals were
      divided into responders (n=9) and nonresponders (n=9) according to whether pHi
      increased or decreased during resuscitation. Hemodynamic and oxygen transport
      variables improved in the group of responders. In the group of nonresponders,
      values decreased. Liver and subcutaneous oxygen tensions increased during the
      initial phase of resuscitation in both groups but decreased after 30 mins in the
      nonresponder group. CONCLUSIONS: The change in pHi during the first hour of
      resuscitation could be used to divide animals treated uniformly from a
      hemodynamic point of view into two distinct groups with seemingly different
      outcome. The minimally invasive method could be of value for early evaluation of
      the results of treatment of hemorrhagic shock.

PMID- 9635664
TI  - Treatment of refractory intracranial hypertension with 23.4% saline.
AB  - OBJECTIVE: To evaluate the effect of intravenous bolus administration of 23.4%
      saline (8008 mOsm/L) on refractory intracranial hypertension (RIH) in patients
      with diverse intracranial diseases. DESIGN: Retrospective chart review. SETTING:
      A neurosciences intensive care unit in a university hospital. PATIENTS: We
      present eight patients and a total of 20 episodes of increased intracranial
      pressure (ICP) resistant to standard modes of therapy. Five patients had
      subarachnoid hemorrhage, one patient had traumatic brain injury, one had a brain
      tumor, and another had spontaneous basal ganglia hemorrhage. Seven patients had
      intraventricular catheters, and one had a subarachnoid pressure screw placed. We
      monitored continuously mean ICP, serum sodium concentrations, mean arterial
      pressure, cerebral perfusion pressure (CPP), central venous pressure, and urine
      output before and after the administration of hypertonic saline (HS). Post mortem
      examination of the brain was performed in two patients. INTERVENTION: Intravenous
      bolus administration of 30 mL of 23.4% saline. MEASUREMENTS AND MAIN RESULTS:
      There was a significant (p < .05) decrease in ICP from a median of 41.5 mm Hg
      before HS to 17 mm Hg at 1 hr, 16 mm Hg at 2 hrs, and 14 mm Hg at 3 hrs after HS
      administration. In 80% of cases, ICP decreased by >50% of the pretreatment value
      over a duration of 21.2+/-10.3 mins. ICP decreased to <20 mm Hg in 65% of all
      cases and the mean time for it to again exceed 20 mm Hg was 6.3+/-4.9 hrs. There
      was a significant improvement in CPP, from 64.7+/-19 (SD) mm Hg before HS to
      85.6+/-18 mm Hg (1 hr) and 83+/-18 mm Hg (3 hrs) after HS. There were no
      significant differences in the other variables measured. The post mortem
      examinations showed no white matter changes or subdural collections. CONCLUSIONS:
      This preliminary case series suggests that the intravenous bolus administration
      of 23.4% saline reduces ICP and augments CPP in patients with resistant increased
      ICP. This reduction can be maintained for several hours while other therapeutic
      measures are being considered. The patient population most likely to respond to
      this therapy needs to be further defined. Although more research is needed, this
      treatment is promising as a new modality for RIH because of its ICP-lowering
      effect without intravascular volume depletion.

PMID- 9635665
TI  - Prognostic value of gastric intramucosal pH in critically ill children.
AB  - OBJECTIVE: To determine the association of tonometrically measured gastric
      intramucosal pH (pHi) to the occurrence of multiple organ dysfunction syndrome
      (MODS) and death in critically ill children. DESIGN: Prospective, observational
      study. SETTING: Pediatric intensive care unit (ICU) of a teaching children's
      hospital. PATIENTS: Fifty-one critically ill children admitted (median age 5.4+/
      5 [SD] yrs; range 1 mo to 16 yrs) with the following diagnoses: post major
      surgery (n=26), sepsis (n=8), multiple trauma (n=5), acute respiratory distress
      syndrome (n=4), and "miscellaneous" (n=8). INTERVENTIONS: Placement of a
      tonometric catheter. MEASUREMENTS AND MAIN RESULTS: Pediatric Risk of Mortality
      (PRISM) score and clinical data were collected on admission and pHi daily during
      their stay in the pediatric ICU. A sigmoid tonometer was used to determine the
      pHi. Unconditional logistic regression was used to investigate the prognostic
      value of pHi. On admission, 26 patients presented with low gastric pHi (< or
      =7.35) and 17 of them had values of <7.30. The mortality rate in children with
      pHi <7.30 was 47.1% (95% confidence interval, 26.2 to 69) in contrast with an
      11.7% mortality rate (95% confidence interval, 4.6 to 26.6) in children having a
      pHi of > or =7.30 (p=.015). The pHi and PRISM score on admission were independent
      predictive factors of death. The risk of mortality is increased when the pHi is
      low (odds ratio=2.5). However, we did not find the pHi to be a predictor for
      developing MODS. CONCLUSIONS: Our results show that pHi is an independent
      predictor of mortality in patients admitted to a pediatric ICU. Although no
      relationship was observed between the risk of MODS and gastric pHi, the
      univariate difference of 21% vs. 41% is highly suggestive. The pHi determination
      is a minimally invasive procedure and well tolerated in children of all ages.

PMID- 9635666
TI  - Accuracy of two pulse oximeters at low arterial hemoglobin-oxygen saturation.
AB  - OBJECTIVE: To evaluate the performance of two pulse oximeters in the measurement
      of arterial hemoglobin saturation in hypoxemic children. DESIGN: Prospective,
      repeated-measures observational study. SETTING: A 16-bed pediatric intensive care
      unit in a children's tertiary hospital. PATIENTS: Sixty-six patients with
      arterial saturation of <90%. INTERVENTIONS: Three arterial blood samples were
      taken from each subject during a 48-hr period. Pulse oximeter measurements of
      arterial saturation were compared with arterial saturation determined by
      cooximetry. MEASUREMENTS AND MAIN RESULTS: Arterial saturation was measured using
      one or both pulse oximeters (SpO2) and compared with the arterial hemoglobin
      saturation determined by cooximetry (SaO2). Sixty-two subjects were studied,
      using the Ohmeda pulse oximeter giving 185 data points (78 with saturations <75%
      [defined by the average of pulse oximeter and cooximeter]); 53 subjects were
      studied, using the Hewlett-Packard pulse oximeter yielding 155 data points (60
      with saturations <75%). SpO2 ranged from 24% to 94%. Bias and precision of the
      Ohmeda pulse oximeter were -2.8% and 4.8% >75% and -0.8% and 8.0% <75%. Bias and
      precision of the Hewlett-Packard pulse oximeter were -0.5% and 5.1% >75% and 0.4%
      and 4.6% <75%. Intrapatient regression coefficient (r) for the differences
      between pulse oximeter and cooximeter was 0.58 for the Ohmeda and 0.59 for the
      Hewlett-Packard. Regression coefficients for predicting change in cooximeter
      value given a change in the Ohmeda pulse oximeter were 0.59 and 0.71 <75% and
      >75%, respectively. Similar coefficients for the Hewlett-Packard pulse oximeter
      were 0.50 and 0.70, respectively. CONCLUSION: The performance of the Ohmeda pulse
      oximeter deteriorated below an SpO2 of 75%. The Hewlett-Packard pulse oximeter
      performed consistently above and below an SpO2 of 75%. The ability of both pulse
      oximeters to reliably predict change in SaO2 based on change in pulse oximetry
      was limited. We recommend measurement of PaO2 or SaO2 for important clinical
      decisions.

PMID- 9635667
TI  - Nomenclature of endothelin peptides.

PMID- 9635668
TI  - Evidence that humans produce less nitric oxide than experimental animals in
      septic shock.

PMID- 9635669
TI  - Therapy of myasthenic crisis.

PMID- 9635670
TI  - Effects of NG-nitro-L-arginine-methyl-ester on cardiopulmonary function and
      biosynthesis of cyclooxygenase products.

PMID- 9635671
TI  - Prolonged extracorporeal life support for varicella pneumonia.

PMID- 9635672
TI  - Smoke gets in your eyes.

PMID- 9635673
TI  - Clear cell carcinoma of the endometrium is characterized by a distinctive profile
      of p53, Ki-67, estrogen, and progesterone receptor expression.
AB  - This study was designed to analyze certain clinicopathological features and the
      profile of p53, Ki-67, estrogen (ER), and progesterone (PR) receptor expression
      of clear cell carcinoma of the endometrium and to determine whether the
      pathogenesis of clear cell carcinoma can be accommodated by a dualistic model of
      endometrial carcinogenesis. In this model, endometrioid carcinoma develops from
      endometrial hyperplasia under unopposed estrogenic stimulation, and serous
      carcinoma develops in atrophic endometrium from a putative precursor lesion
      designated endometrial intraepithelial carcinoma (EIC). Twenty-one clear cell
      carcinomas of the endometrium were analyzed and compared with 77 endometrioid
      carcinomas of all grades and 30 serous carcinomas. Clear cell carcinomas showed a
      distinctive immunoprofile characterized by immunonegativity for ER and PR, low
      immunoreactivity for p53, and a high Ki-67 proliferation index. ER, PR, and Ki-67
      expression were similar to serous carcinoma, but p53 expression was significantly
      lower in clear cell carcinoma (P < .05). ER and PR expression were significantly
      lower, and the Ki-67 proliferation index was significantly higher in clear cell
      carcinoma compared with endometrioid carcinomas (P < .05). p53 expression tended
      to be higher in clear cell carcinoma compared with endometrioid carcinoma, but
      the difference was not statistically significant. In contrast to endometrioid
      carcinoma, clear cell carcinoma was rarely associated with endometrial
      hyperplasia and serous carcinoma was not. Subdividing clear cell carcinoma
      morphologically into one that resembled serous carcinoma (clear cell carcinoma
      with serous features) and another that did not (typical clear cell carcinoma)
      showed that clear cell carcinoma with serous features had a higher Ki-67
      proliferation index than typical clear cell carcinoma, although expression of ER,
      PR, and p53 were similar. Clear cell carcinoma with serous features was
      associated with EIC in 50% and was not associated with endometrial hyperplasia.
      In contrast, typical clear cell carcinoma was associated with endometrial
      hyperplasia in 40% and was not associated with EIC. In summary, this study
      provides evidence that clear cell carcinoma of the endometrium, like serous
      carcinoma, is estrogen independent and shows a high Ki-67 proliferation index. In
      contrast to serous carcinoma, strong p53 expression occurred less frequently in
      clear cell carcinoma and predominantly in clear cell carcinoma with serous
      features. The findings suggest that the molecular events that underlie the
      development of clear cell carcinoma differ from those of endometrioid and serous
      carcinoma.

PMID- 9635674
TI  - Altered expression of the p53-regulated proteins, p21Waf1/Cip1, MDM2, and Bax in
      ultraviolet-irradiated human skin.
AB  - The distribution of p21WAf1/CiP1, MDM2, and Bax/Bcl-2 proteins in ultraviolet
      (UV)-irradiated and nonirradiated human skin was examined immunohistochemically
      and compared with p53 protein levels. Sun-protected buttock skin from three
      volunteers was exposed to solar simulated irradiation, and biopsies were
      performed 0.5, 1, 2, 4, and 24 hours after irradiation as well as control
      unirradiated skin from the opposite buttock. A similar staining pattern was
      observed in each of the three volunteers. P53 protein was detectable in all skin
      samples examined. P21Waf1/CiP1 protein was visible in the nuclei of cells at 4
      hours, and staining intensity increased at 24 hours. MDM2 protein expression was
      noted in isolated nuclei in the epidermis at 24 hours. Bax cytoplasmic staining
      was evident in the basal layer of the epidermis of all samples, and this staining
      appeared to increase in intensity in the 4- and 24-hour specimens. There was no
      Bcl-2 immunohistochemical staining in any sample. These results suggest that p53
      and genes/proteins under the control of p53 are altered/ activated in normal
      human skin in response to UV exposure.

PMID- 9635675
TI  - Ret oncogene activation in papillary thyroid carcinoma: prevalence and
      implication on the histological parameters.
AB  - The Ret proto-oncogene is known to be rearranged in papillary carcinoma of the
      thyroid. The aim of this study was to investigate the in situ expression of Ret
      mRNA in thyroid tumors. Formalin-fixed, paraffin-embedded tissue specimens from
      45 thyroid lesions were examined by in situ hybridization using manual capillary
      action technology (MicroProbe Staining System) and a 52-base synthetic
      biotinylated oligonucleotide probe complementary to the tyrosine-kinase domain of
      Ret proto-oncogene. The clinicopathological features of these patients with
      thyroid lesions also were noted. Ret was noted in 17 (43%) of 40 papillary
      carcinomas. In contrast, none of the three follicular carcinomas, follicular
      adenoma, nodular hyperplasia, and normal thyroids, showed evidence of Ret mRNA.
      Our results showed that, in papillary thyroid carcinoma, there is an important
      role of Ret activation. The Ret staining could be a useful marker for papillary
      carcinoma.

PMID- 9635676
TI  - Epstein-Barr virus-related posttransplantation lymphoproliferative disorder
      involving pancreas allografts: histological differential diagnosis from acute
      allograft rejection.
AB  - The clinical and pathological features of acute pancreas allograft rejection and
      involvement of the graft by posttransplantation lymphoproliferative disorders
      (PTLD) overlap. Because the treatment is diametrically opposite in these two
      types of lesions, an accurate diagnosis is essential. The histological features
      in pancreas allograft needle biopsy specimens (n=7) and pancreatectomies (n=4)
      from four patients with Epstein-Barr virus (EBV)-related PTLD were compared with
      the material from 14 patients who did not develop PTLD after 12 to 58 months of
      follow-up and whose biopsy specimens (n=10) and pancreatectomies (n=10) showed
      rejection-related heavy or atypical inflammatory infiltrates. Features typical of
      rejection included most (>75%) being of mixed small and large, activated
      appearing T lymphocytes, a smaller component of mature plasma cells, and variable
      numbers of eosinophils. Cytologically atypical cells were always a minority (<
      10%). The inflammation involved the septal spaces with proportional involvement
      of the exocrine tissue, veins, ducts, and arteries. The inflammation was
      particularly targeted against the acini and was associated with acinar cell
      damage. Features characteristic of PTLD were nodular and expansile infiltrates,
      composed of a significant proportion of atypical, plasmacytoid B cells (40% to
      70% of the infiltrate); Reed-Sternberg-like cells were noted in two patients. The
      infiltrates involved the parenchyma randomly with no apparent affinity for the
      acinar tissue. Extensive infiltration of the peripancreatic soft tissues was
      common. Arterial walls were not involved in PTLD unless there was concurrent
      acute vascular rejection. Features identified in both conditions were foci of
      necrosis and infiltration of venous walls with associated endotheliitis. Samples
      with concurrent PTLD and acute rejection showed combinations of these features.
      In situ hybridization for EBER (Epstein-Barr-encoded RNAs) was positive only in
      the samples from patients with PTLD. Based on the assessment of morphological
      differences and the selective use of relatively simple ancillary techniques, PTLD
      can be correctly diagnosed even in small tissue samples such as needle biopsy
      specimens. An early diagnosis will lead to the appropriate treatment.

PMID- 9635677
TI  - Characterization of Coxsackie B virus RNA in myocardium from patients with
      dilated cardiomyopathy by nucleotide sequencing of reverse transcription-nested
      polymerase chain reaction products.
AB  - This study was performed to detect and characterize the enterovirus present in
      myocardium of some patients with heart muscle disease by nucleotide sequencing of
      polymerase chain reaction (PCR) products after amplification with enterovirus
      group-specific primers. Enterovirus sequences have been detected previously in
      myocardium of patients with myocarditis or dilated cardiomyopathy and seem
      causal, although the particular virus serotypes involved have not been
      identified. In a prospective study of endomyocardial biopsy specimens from 35
      consecutive patients with suspected heart muscle disease, enterovirus sequences
      from the 5' nontranslated region were amplified by reverse transcription-nested
      PCR using group-specific primers. This region contains both conserved and
      variable sequence motifs, characteristic of particular enterovirus serotypes. The
      nucleotide sequences of individual PCR products were determined by cycle
      sequencing and compared with all known sequences (GenBank/EMBOL), using the GCG
      software package. Endomyocardial biopsy specimens from 9 of 21 (42.9%) patients
      with a histologically confirmed diagnosis of dilated cardiomyopathy were positive
      for enterovirus by PCR, compared with only 1 of 14 (7.1%) patients with other
      myocardial pathological conditions (Fisher's exact probability=0.0275: odds
      ratio=9.75; 95% confidence interval=1.31-72.78). The nucleotide sequence of the
      PCR products differed, indicating no cross-contamination. However, computerized
      comparison showed that each had greatest homology with the 5' nontranslated
      region of Coxsackie B virus but contained up to 11% sequence variations compared
      with the prototype Coxsackie B3 strain Nancy. Parallel investigation of tissue
      from our mouse model of Coxsackievirus B3-induced myocarditis showed that
      nucleotide sequence changes are not introduced by reverse transcription or PCR.
      These data support the link between enteroviral infection and dilated heart
      muscle disease and suggest that Coxsackie B serotypes are the enteroviruses most
      frequently involved.

PMID- 9635678
TI  - Analysis of immunoglobulin genes in splenic marginal zone lymphoma suggests
      ongoing mutation.
AB  - Splenic marginal zone lymphoma (SMZL) is a low-grade primary splenic B cell
      lymphoma, originally thought to be related to splenic marginal zone B cells.
      Later studies showed that SMZL sometimes may be accompanied by villous
      lymphocytes in the peripheral blood, a condition previously characterized as
      splenic lymphoma with villous lymphocytes (SLVL). The relationship between SMZL
      and splenic marginal zone B cells has recently been called into question. We
      report four further cases of SMZL, two of which were associated with villous
      lymphocytes in the peripheral blood. In addition to immunophenotypical analysis,
      we have studied the IgV(H) genes in each case, because the extent and patterns of
      their mutation can indicate the normal B cell counterpart of lymphomas. The
      IgV(H) genes in the four cases of SMZL studied are mutated, which is consistent
      with their origin from postfollicular marginal zone B cells. Evidence of ongoing
      mutation was also observed. This contrasts with a study showing that blood-borne
      tumor cells in SLVL show no sign of ongoing mutation. It is possible that the
      ongoing mutations in the cases studied here are acquired in a splenic
      microenvironment, such as that found in the follicle center.

PMID- 9635679
TI  - MDR1 expression is associated with adverse survival in melanoma of the uveal
      tract.
AB  - Metastatic uveal melanoma is profoundly chemoresistant and has a very poor
      outcome. We have previously shown that the MDR1 gene and its gene product P
      glycoprotein (P-gp), which are known to cause drug resistance in cancer cells,
      are expressed in ocular melanoma. Overexpression of MDR1 has been associated with
      a poor survival in some tumor types treated by chemotherapy and in some untreated
      tumours. To assess whether MDR1 expression is of prognostic value in uveal
      melanoma, we evaluated the expression of MDR1 by immunohistochemistry in 108
      cases. Three semiquantitative grades were used to evaluate positive staining. We
      detected MDR1 expression in 80% of cases; 28% showed grade I staining; 30%, grade
      II staining; and 22%, grade III staining. There was a statistically significant
      association (P=.004) between MDR1 expression by tumor cells and shorter survival
      times (n=96), which was most striking at grade III levels of expression.
      Multivariate analysis showed that MDR1 expression is an independent prognostic
      indicator of poor survival. We conclude that (1) MDR1 may be involved in
      chemoresistance and tumor propagation in primary uveal melanoma, and (2)
      increasing levels of expression are prognostically significant and may prove a
      useful marker of tumor invasiveness, independent of established prognostic
      factors.

PMID- 9635680
TI  - Telomerase expression in gliomas including the nonastrocytic tumors.
AB  - Telomerase is a ribonucleoprotein that consists of a RNA component for
      synthesizing telomeric DNA repeats onto chromosome ends, so that telomere length
      can be maintained; telomerase activation in general signifies immortalization of
      cells. Because the telomerase activity of only a few cases of nonastrocytic
      gliomas and low-grade astrocytic gliomas have been examined before, telomerase
      activity from a broad spectrum of astrocytic and nonastrocytic gliomas were
      examined in this study. A total of 119 brain tumor samples, including 16
      pilocytic astrocytomas, one dysembryoplastic neuroepithelial tumor (DNT), two
      pleomorphic xanthoastrocytomas (PXA), 15 ependymomas, 21 oligodendrogliomas, 13
      grade II astrocytomas, 13 anaplastic astrocytomas, and 38 glioblastoma multiforme
      tumors (GBM), were studied, using a polymerase chain reaction (PCR)-based
      telomeric repeat amplification protocol assay. All pilocytic astrocytomas, DNT,
      PXA, and myxopapillary ependymomas were telomerase negative. Three of 13 (15.4%)
      classical ependymomas, 2 of 14 (14.3%) grade II oligodendrogliomas, and three of
      seven (42.9%) anaplastic oligodendrogliomas had detectable telomerase activity.
      The frequency of telomerase expression in ependymomas and oligodendrogliomas was
      lower than those observed in astrocytic tumors: fibrillary astrocytoma, 23.1%;
      anaplastic astrocytoma, 23.1%; and GBM, 26.3%. The mean age of telomerase
      positive GBM patients (61.7 years) was significantly higher than that of
      telomerase-negative GBM patients (47.8 years, P=.002). These results suggest that
      telomerase activation may occur early in glial tumorigenesis, and astrocytomas
      may have mechanisms of immortalization other than telomerase activation.

PMID- 9635681
TI  - Allelic loss on chromosome 22q in epithelioid sarcomas.
AB  - Epithelioid sarcomas are soft tissue tumors with an indolent, but potentially
      aggressive, clinical behavior. Distinction from other benign and malignant
      entities may be a diagnostic dilemma. In this study, we evaluate the presence of
      loss of heterozygosity (LOH) of chromosome 22q in tumor DNA from 13 epithelioid
      sarcomas, four epithelioid angiosarcomas, and two epithelioid
      hemangioendotheliomas, and investigate its possible role in diagnosis. LOH was
      detected in 6 of 10 (60%) of the informative epithelioid sarcomas. No allele loss
      was detected in the informative vascular tumors, three angiosarcomas, and two
      hemangioendotheliomas. Chromosome 22q carries the locus of a tumor suppressor
      gene, the neurofibromatosis 2 (NF2) gene, which has been shown to be lost or
      mutated in some NF2-related tumors, sporadic meningiomas, and vestibular
      schwannomas, as well as a few other tumors. Our data suggest that a region of
      chromosome 22q may be the locus of a tumor suppressor gene involved in the
      tumorigenesis of these neoplasms. Genetic alterations of yet-unknown tumor
      suppressor genes in this region, or even the NF2 tumor suppressor gene, may play
      a role in epithelioid sarcomas tumorigenesis. The fact that LOH was only detected
      in epithelioid sarcomas and not in the vascular tumors studied suggests a
      possible role for this marker in diagnosis.

PMID- 9635682
TI  - Distinction of basaloid squamous cell carcinoma from adenoid cystic and small
      cell undifferentiated carcinoma by immunohistochemistry.
AB  - Basaloid squamous cell carcinoma (BSCC) is a recently recognized variant of
      squamous cell carcinoma (SCC) with a predilection to occur in the tongue base,
      hypopharynx, and supraglottic larynx. In smal biopsy specimens, these tumors can
      be difficult to distinguish from small cell undifferentiated carcinoma (SCUC) and
      adenoid cystic carcinoma (ACC). Monoclonal antibodies reactive with cytokeratin
      (AE1/AE3, 34betaE12, Cam 5.2) as well as a variety of other cellular antigens
      (vimentin, actin, desmin, chromogranin, synaptophysin, CD57, neuron-specific
      enolase [NSE], and S100) were used in an immunoperoxidase method with paraffin
      embedded tissue to phenotypically characterize 23 cases of BSCC, 10 cases of
      SCUC, and 15 cases of ACC. The neoplastic cells in 22 of the 23 cases of BSCC
      reacted with the high-molecular-weight cytokeratin antibody 34betaE12, whereas no
      reactivity was seen in any of the 10 cases of SCUC. This pattern of 34betaE12
      reactivity more consistently differentiated BSCC from SCUC than did reactivity
      with the neuroendocrine markers chromogranin, synaptophysin, CD57, and NSE. These
      findings show that immunoperoxidase stains performed on paraffin-embedded tissue
      are potentially useful in establishing a diagnosis of basaloid squamous cell
      carcinoma.

PMID- 9635683
TI  - Loss of p53 function in uterine papillary serous carcinoma.
AB  - In contrast to endometrioid carcinoma, uterine papillary serous carcinoma (UPSC)
      is an aggressive type of endometrial cancer. Loss of p53 function is critical for
      the molecular pathogenesis of UPSC. Both UPSC and its putative precursor,
      endometrial intraepithelial carcinoma (EIC), show abnormal p53 overexpression in
      most tumors. To further assess the nature of p53 alterations in UPSC, we
      systematically reevaluated a subset of our previous cohort of UPSC patients. In
      the current study, we correlate mutations of the p53 gene as detected by direct
      sequencing of exons 5 through 8 with p53 accumulation and expression of Waf-1 in
      32 UPSC tumors. Waf-1 is a downstream effector of p53-mediated G1 arrest after
      DNA damage and, thus, an indicator of p53 functionality. Although 78% of tumors
      exhibited strong nuclear p53 immunoreactivity in 100% of tumor cells, we were
      able to detect p53 mutations in 53%. As expected, all p53 mutant tumors (17
      cases) exhibited p53 overexpression. Seventy percent of those (12 tumors) showed
      concomitant lack of Waf-1 expression consistent with transcriptionally inactive
      p53, whereas the other five tumors showed Waf-1 staining in only a minor fraction
      of tumor cells consistent with p53-independent Waf-1 expression. In contrast, 47%
      (15 cases) of tumors failed to exhibit p53 mutations; interestingly, more than
      half of those (eight cases) showed strong nuclear p53 accumulation in all tumor
      cells but lacked concomitant Waf-1 expression. These findings are consistent with
      a mutation-dependent and -independent type of p53 inactivation in UPSC that are
      both associated with nuclear overexpression. Our findings suggest that the
      combined immunocytochemical analysis of p53 and Waf-1 is a valuable means of
      assessing the functional status of p53. In summary, p53 alterations are common in
      UPSC and probably responsible for its aggressive biological behavior.

PMID- 9635684
TI  - Digital image analysis of proliferative index: two distinct populations of high
      grade prostatic intraepithelial neoplasia in close proximity to adenocarcinoma of
      the prostate.
AB  - A considerable amount of data has been collected showing the association of high
      grade prostatic intraepithelial neoplasia (HGPIN) with adenocarcinoma of the
      prostate, and many studies have yielded results that suggest that HGPIN is a
      precursor of carcinoma. A few studies have indicated that HGPIN may, in some
      cases, be a sequela of prostatic adenocarcinoma. We examined the proliferative
      indices of HGPIN, carcinoma, and benign prostatic epithelium by computer-aided
      counting of Ki-67-positive nuclei in 15 cases in which HGPIN and carcinoma were
      in close proximity. There were 13 radical prostatectomy specimens with prostate
      cancer and two cystoprostatectomy specimens with both transitional cell carcinoma
      and prostatic adenocarcinoma. First, we showed the accuracy of the computer-aided
      counting method compared with direct counting through the binoculars of the
      microscope. Then proliferative activity was assessed for each case by picking the
      two areas of carcinoma, the two areas of HGPIN, and the one area of benign
      epithelium with the greatest density of carcinomatous, dysplastic, and benign Ki
      67-positive nuclei, respectively. The total number of nuclei and the number of
      positive nuclei were counted. Basal cells were not counted. The mean
      proliferative index was higher for cancer (caindex, average 0.054) than for HGPIN
      (pinindex, average 0.048) (P < .05). We found that the 15 cases fell into two
      distinct groups. The average ratio of pinindex to caindex (pinindex/caindex) was
      lower in group 1 (0.72) than in group 2 (1.54) (P=.17), and when the results were
      corrected for the nonzero gamma-intercepts of the regression lines of pinindex
      versus caindex, the ranges were widely separated, and the difference between the
      means was statistically significant (0.15 v 0.62; P < .0001). A greater
      subjective similarity between the nuclear features in the HGPIN and those of the
      corresponding carcinoma was noted for the cases in group 2. The average value of
      bngnindx was 0.014. The value of bngnindx did not correlate with either caindex
      or pinindex. We conclude that there may be two types of lesions with the
      morphological appearance of HGPIN and that they may have different relationships
      to carcinoma. Computer-aided counting of digitized microscopic images is both
      labor-saving and as accurate as enumeration directly through the binoculars of
      the microscope.

PMID- 9635685
TI  - CD44V6 expression in human colorectal carcinoma.
AB  - CD44 is an adhesion molecule involved in cell-to-cell and cell-to-matrix
      interactions. This transmembrane glycoprotein exists in either standard or
      variant forms, originated by alternative splicing. One of the isoforms (CD44V6)
      has been shown, in some systems, to modify the metastatic potential of tumor
      cells. To investigate the role of this biomarker as possible prognostic antigen
      in colorectal cancer, we immunohistochemically analyzed the distribution of
      CD44V6 expression on formalin-fixed, paraffin-embedded tissues from resected
      colorectal cancers of 34 patients. The monoclonal antibody VFF7 against the amino
      acid sequence encoded by exon CD44V6 was applied using the avidin-biotin
      peroxidase method. For each resected specimen, normal (N), adenomatous (AD), and
      carcinomatous (CA) colonic mucosa were tested. In 68% of the resected cases,
      these areas were present in the same slide, and in 76% of cases, nodal or liver
      metastases (MT) were available for evaluation. Adenomatous polyp biopsy specimens
      of 10 carcinoma-free patients were also tested. In selected cases, CD44V6
      expression was also determined using the Western blot immunoprecipitation
      technique. CD44V6 immunoreactivity was detected in 100% of the ADs, and in 91% of
      CAs, but was mostly weak in only 38% of MTs (n=26). In 49% (n=35) of ADs, 11%
      (n=34) of CAs, and 4% of MTs (n=26), the stain was moderate to strong. CD44V6
      immunoreactivity was predominantly membranous in ADs and cytoplasmic in MTs. In
      the CAs, both staining patterns were noted. Interestingly, the normal mucosa had
      a weak subnuclear localization of the stain. In the cases evaluated by Western
      blotting immunoprecipitation analysis, the level of CD44V6 protein expression was
      similar to that obtained by immunohistochemistry. No correlation was found with
      tumor type, stage, or patient survival. The predominant CD44V6 expression in ADs
      and CAs, but not in MTs, suggests that, in many cases, the expression of this
      adhesion molecule may be lost during the acquisition of migratory function by the
      tumor cells.

PMID- 9635686
TI  - The histological spectrum of hemangiopericytoma: application of
      immunohistochemical analysis including proliferative markers to facilitate
      diagnosis and predict prognosis.
AB  - Hemangiopericytoma (HPC) is an uncommon vascular neoplasm thought to be derived
      from pericytes. Prediction of patient outcome is difficult based what is
      currently known about these tumors and histological parameters alone. We compiled
      27 cases of HPC and evaluated the spectrum of histological features to
      investigate whether there was any correlation between histology, immunostaining,
      prognostic markers, and patient outcome. The following parameters were evaluated:
      vasculature, histological pattern (solid, myxoid, trabecular, alveolar), degree
      of cellular pleomorphism, necrosis, mitoses, and giant cell content.
      Immunohistochemistry was performed to determine the reactivity for CD 31, CD34,
      vimentin, actin, cytokeratin, S100, actin, and SMA. Proliferative rate was
      analyzed using antibodies to PCNA and MIB1. Patient's age ranged from 8 months to
      75 years (mean, 35; median, 31). Twenty of 27 cases were located in the
      extremities. The tumors were grossly described as lobulated and well
      circumscribed (n=12) and nonencapsulated (n=15). By histology, the characteristic
      ramifying or staghorn vasculature pattern was seen in all cases. A solid
      histological pattern was mixed with an alveolar pattern in three cases,
      trabecular pattern in six cases, and myxoid pattern in two cases. Tumor cells
      were uniform, polygonal to spindle-shaped, often with vesicular nuclei. Tumor
      giant cells were present in 9 of 27 cases; necrosis, in 11 of 27. Mitoses ranged
      from 0 to 14 per 10 high-power fields (HPF). Cellular pleomorphism was 1+ in nine
      cases, 2+ in 12 cases, and 3+ in six cases. Immunohistochemistry showed
      reactivity for CD34 and vimentin in all cases. Actin was focally positive in one
      case, and SMA was focally positive in another. CD 31, cytokeratin, and S100 were
      uniformly nonreactive. Proliferative index measured by PCNA and MIBI ranged
      between less than 1% and 40% of tumor cells. Follow-up was available in 22 cases
      and ranged from 1 year to 15 years. Seven patients had metastases, and two
      recurred locally. Thirteen patients had no evidence of disease at last checkup.
      Parameters associated with recurrences or metastases include a trabecular
      pattern, the presence of necrosis, mitoses, vascular invasion, and cellular
      pleomorphism. Features associated with an aggressive biological behavior can be
      identified histologically. There was some, but not total, correlation between
      proliferative markers and tumor aggressiveness.

PMID- 9635687
TI  - Papillary immature metaplasia (immature condyloma) of the cervix: a
      clinicopathologic analysis and comparison with papillary squamous carcinoma.
AB  - Papillary immature metaplasia (PIM) is a variant of human papillomavirus (HPV) 6
      or 11 infection. PIM resembles an immature metaplasia but has filiform papillae,
      variable cytological atypia, and, frequently, extension into the endocervical
      canal. Because the unusual morphology and presentation of PIM may cause confusion
      between this and other benign and malignant papillary neoplasms, we conducted a
      clinicopathologic analysis of PIM and compared expression of Ki-67 between PIM,
      condyloma, and papillary carcinoma. Data on patient age, duration of the lesions,
      and procedures, including cone biopsy, were obtained. The distribution and
      intensity of staining for Ki-67 in the epithelium was recorded and compared with
      both condyloma and papillary carcinoma. HPV typing was performed by polymerase
      chain reaction (PCR) and restriction fragment length pleomorphism analysis
      (RFLP). Ten of 13 PIMs were HPV 6/11 positive. Three cases contained areas
      closely resembling condyloma. Eleven cone biopsies were performed on nine cases.
      Three were found to have a coexisting high-grade squamous intraepithelial lesion
      that was either HPV 6/11 negative or contained another HPV type. All PIMs
      displayed variable staining for Ki-67 with a low index of staining in the mid and
      upper epithelial layers. In contrast, areas of condyloma had significantly
      stronger staining in areas with viral cytopathic effect (koilocytosis). Six
      papillary carcinomas were analyzed and displayed moderate to diffuse staining,
      including staining of the superficial cell nuclei. PIM is a distinct pathological
      subset of cervical condyloma that frequently is managed by cone biopsy and may
      persist. The marked reduction in Ki-67 staining in superficial cell layers
      distinguishes PIM from some condylomata and most HSILs and papillary carcinomas.
      Immunostaining thus may be helpful in distinguishing PIM from papillary
      carcinoma, although the differentiation of the two is best made on morphological
      grounds.

PMID- 9635688
TI  - Cat-scratch disease simulating Histiocytosis X.
AB  - Cat-scratch disease is a self-limited condition commonly causing a benign chronic
      lymphadenopathy in children. Osteolytic lesions are a rare complication, but have
      been previously reported. We report a case of a solitary osteolytic lesion of the
      skull whose clinical, radiographic and pathological features were initially
      interpreted as being consistent with Histiocytosis X. Subsequently, positive
      serological titers for Bartonella, a history of a cat-scratch antecedent to the
      onset of clinical symptoms and review of the original histopathology confirmed
      the diagnosis of cat-scratch disease. We reviewed the English language literature
      on osteolytic lesions associated with cat-scratch disease and compare the current
      case with those previously reported.

PMID- 9635689
TI  - Massive macrophage lipid accumulation presenting as hepatosplenomegaly and
      lymphadenopathy associated with long-term total parenteral nutrition therapy for
      short bowel syndrome.
AB  - We present a unique case of massive splenomegaly, hepatomegaly, and
      lymphadenopathy caused by lipid-laden macrophages in a 50 year old white female
      with short-bowel syndrome treated with long-term total parenteral nutrition.
      Using transmission electron microscopy and special stains we were able to show
      that the total parenteral nutrition lipid component was composed of lipid
      droplets and micelles morphologically identical to those found in lipid-laden
      macrophages which had accumulated in the patient's reticuloendothelial system
      leading to massive splenomegaly, hepatomegaly (without evidence of steatosis) and
      lymphadenopathy. While this phenomenon has been reported in animal models, no
      human cases have been previously reported.

PMID- 9635690
TI  - Primary aneurysmal cyst of soft tissue: serial magnetic resonance imaging study.

PMID- 9635691
TI  - Malignant mesothelioma presenting as colonic tumor.

PMID- 9635692
TI  - Bronchiolitis obliterans, Castleman's disease, and a bullous disease: pemphigus
      vulgaris or paraneoplastic pemphigus?

PMID- 9635693
TI  - Dose escalation with three-dimensional conformal radiation therapy affects the
      outcome in prostate cancer: will more prove better?

PMID- 9635694
TI  - Dose escalation with three-dimensional conformal radiation therapy affects the
      outcome in prostate cancer.
AB  - PURPOSE: Three-dimensional conformal radiation therapy (3D-CRT) is a technique
      designed to deliver prescribed radiation doses to localized tumors with high
      precision, while effectively excluding the surrounding normal tissues. It
      facilitates tumor dose escalation which should overcome the relative resistance
      of tumor clonogens to conventional radiation dose levels. The present study was
      undertaken to test this hypothesis in patients with clinically localized prostate
      cancer. METHODS AND MATERIALS: A total of 743 patients with clinically localized
      prostate cancer were treated with 3D-CRT. As part of a phase I study, the tumor
      target dose was increased from 64.8 to 81 Gy in increments of 5.4 Gy. Tumor
      response was evaluated by post-treatment decrease of serum prostate-specific
      antigen (PSA) to levels of < or = 1.0 ng/ml and by sextant prostate biopsies
      performed > or = 2.5 years after completion of 3D-CRT. PSA relapse-free survival
      was used to evaluate long-term outcome. The median follow-up was 3 years (range:
      1-7.6 years). RESULTS: Induction of an initial clinical response was dose
      dependent, with 90% of patients receiving 75.6 or 81.0 Gy achieving a PSA nadir <
      or = 1.0 ng compared with 76% and 56% for those treated with 70.2 Gy and 64.8 Gy,
      respectively (p < 0.001). The 5-year actuarial PSA relapse-free survival for
      patients with favorable prognostic indicators (stage T1-2, pretreatment PSA < or
      = 10.0 ng/ml and Gleason score < or = 6) was 85%, compared to 65% for those with
      intermediate prognosis (one of the prognostic indicators with a higher value) and
      35% for the group with unfavorable prognosis (two or more indicators with higher
      values) (p < 0.001). PSA relapse-free survival was significantly improved in
      patients with intermediate and unfavorable prognosis receiving > or = 75.6 Gy (p
      < 0.05). A positive biopsy at > or = 2.5 years after 3D-CRT was observed in only
      1/15 (7%) of patients receiving 81.0 Gy, compared with 12/25 (48%) after 75.6 Gy,
      19/42 (45%) after 70.2 Gy, and 13/23 (57%) after 64.8 Gy (p < 0.05). CONCLUSIONS:
      The data provide evidence for a significant effect of dose escalation on the
      response of human prostate cancer to irradiation and defines new standards for
      curative radiotherapy in this disease.

PMID- 9635695
TI  - Dose escalation with 3D conformal treatment: five year outcomes, treatment
      optimization, and future directions.
AB  - PURPOSE: To report the 5-year outcomes of dose escalation with 3D conformal
      treatment (3DCRT) of prostate cancer. METHODS AND MATERIALS: Two hundred thirty
      two consecutive patients were treated with 3DCRT alone between 6/89 and 10/92
      with ICRU reporting point dose that increased from 63 to 79 Gy. The median follow
      up was 60 months, and any patient free of clinical or biochemical evidence of
      disease was termed bNED. Biochemical failure was defined as prostate-specific
      antigen (PSA) rising on two consecutive recordings and exceeding 1.5 ng/ml.
      Morbidity was reported by the Radiation Therapy Oncology Group (RTOG) scale, the
      Late Effects Normal Tissue (LENT) scale, and a Fox Chase modification of the
      latter (FC-LENT). All patients were treated with a four-field technique with a 1
      cm clinical target volume (CTV) to planning target volume (PTV) margin to the
      prostate or prostate boost; the CTV and gross tumor volume (GTV) were the same.
      Actuarial rates of outcome were calculated by Kaplan-Meier and cumulative
      incidence methods and compared using the log rank and Gray's test statistic,
      respectively. Cox regression models were used to establish prognostic factors
      predictive of the various measures of outcome. Five-year Kaplan-Meier bNED rates
      were utilized by dose group to estimate logit response models for bNED and late
      morbidity. RESULTS: PSA <10 ng/ml: No dose response was demonstrated using
      estimated bNED rates or by analysis of PSA nadir vs. dose. PSA 10-19.9 ng/ml: A
      bNED dose response was demonstrated (p = 0.02) using the log rank test. The logit
      response model showed 5-year bNED rates of 35% at 70 Gy and 75% at 76 Gy (p =
      0.0049) and illustrated the relative ineffectiveness of conventional dose
      treatment. PSA 20+ ng/ml: A bNED dose response was demonstrated (p = 0.02) using
      the log rank test. The logit response model indicated a 5-year bNED rate of 10%
      at 70 Gy and 32% at 76 Gy (p = 0.10). Morbidity: Dose response was demonstrated
      for FC-LENT grade 2 and grade 3,4 GI morbidity and for LENT grade 2 GU sequelae.
      RTOG grade 3,4 GI morbidity at 5 years was <1%. Factors associated with bNED,
      cause-specific survival, and metastasis were studied using Cox multivariate
      analysis. Pretreatment PSA (p = 0.0001), Gleason score 7-10 (p = 0.0001), and
      dose (p = 0.017) were significantly predictive of bNED. For each 1 Gy increase in
      dose, the hazard of bNED failure decreased by 8%. Palpation stage was associated
      with cause-specific survival (p = 0.002) and distant metastasis (p = 0.0004).
      Gleason score was also predictive of distant metastasis (p = 0.02). CONCLUSIONS:
      A dose response was observed for patients with pretreatment PSA >10 ng/ml based
      on 5-year bNED results. No dose response was observed for patients with
      pretreatment PSA < 10 ng/ml. Dose response was observed for FC-LENT grade 2 and
      grade 3,4 GI sequelae and for LENT grade 2 GU sequelae. Optimization of treatment
      was made possible by the results in this report. The improvement in 5-year bNED
      rates for patients with PSA levels > 10 ng/ml strongly suggests that clinical
      trials employing radiation should investigate the use of 3DCRT and prostate doses
      of 76-80 Gy.

PMID- 9635696
TI  - Changes in biochemical disease-free survival rates as a result of adoption of the
      consensus conference definition in patients with clinically localized prostate
      cancer treated with external-beam radiotherapy.
AB  - PURPOSE: The optimal definition of biochemical recurrence of prostate cancer
      after definitive radiotherapy remains elusive. Different institutions have
      developed their own definitions, and a consensus conference (CC) sponsored by the
      American Society for Therapeutic Radiology and Oncology has recently proposed
      another definition. This study compares the definition previously used at our
      institution with the definition proposed by the CC. METHODS: Two hundred and
      eight patients were treated for localized prostate cancer with conformal external
      beam radiotherapy between 1989-1993 at our institution and followed for at least
      24 months. Patients were categorized as failures according to our institutional
      definition and the CC definition. Our definition (CPMC) required two increases in
      serum prostate specific antigen (PSA) over at least a 3-month period with a final
      value of at least 1 ng/ml or a single value resulting in clinical intervention.
      The CC definition required three consecutive increases in PSA. This was modified
      to also consider those patients with one or two increases leading to clinical
      intervention as failures. Differences in the failure rates between the two
      definitions were evaluated and factors influencing these differences were
      explored. In an additional analysis, CC was modified such that patients with one
      or two PSA increases were censored at the time of the PSA prior to the increases
      (CC-II), rather than at the last PSA (CC). The median follow-up time was 31
      months. RESULTS: There were 36 fewer failures according to CC (n = 96) compared
      with CPMC (n = 132) (p < 0.001). Twenty cases called failures by CPMC
      subsequently had a decrease in PSA ("false failures"). The other 16 patients have
      had two increases in PSA, but are awaiting their next follow-up visit to obtain a
      third PSA ("pending failures"). Analysis of factors predicting "pending failures"
      showed Gleason score to be the sole predictor of this change in status in
      multivariate analysis (p = 0.03) with patients with lower-grade tumors being more
      likely to change status (Gleason 2-6: 15% vs. Gleason 7-10: 1%). On the other
      hand, "false failures," compared to true failures, had a lower mean PSA nadir
      (1.7 ng/ml vs. 7.0 ng/ml, p < 0.001) and significantly smaller mean increases in
      PSA (1st increase: 0.6 ng/ml vs. 3.4 ng/ml, p = 0.006; 2nd increase: 0.4 ng/ml
      vs. 4.8 ng/ml, p = 0.002). In 85% (17 of 20) of these patients, at least one of
      the increases was < or = 0.3 ng/ml compared with 44% (42 of 96) of the true
      failures (p = 0.0008). CC-II resulted in a small decrease in BDFS rates compared
      with CC, but did not affect the overall difference between CC and CPMC. A
      modified definition that defines failure as two consecutive increases in PSA over
      3 months, with a final value greater than 1.0 ng/ml and each increase being at
      least 0.3 ng/ml, or three consecutive increases would result in a "false" failure
      rate of only 3% (3 of 99) and identify 56% (54 of 96) of the true failures after
      only two PSA increases. CONCLUSION: The CPMC definition of two PSA increases can
      falsely identify patients as failures, particularly if the increases in PSA are
      small (i.e., < or = 0.3 ng/ml). The CC definition requiring three increases in
      PSA can falsely identify patients as disease-free when the time to failure is
      long relative to the follow-up time. We propose a that a definition that combines
      aspects of both definitions (two consecutive increases in PSA over 3 months, with
      a final value greater than 1.0 ng/ml and each increase being at least 0.3 ng/ml,
      or three consecutive increases) may be a better definition of biochemical
      failure.

PMID- 9635697
TI  - The treatment of nonpalpable PSA-detected adenocarcinoma of the prostate with 3
      dimensional conformal radiation therapy.
AB  - PURPOSE: We reviewed our institution's experience treating patients with
      nonpalpable PSA-detected prostate cancer with three-dimensional conformal
      radiation therapy (3DCRT) to determine prognostic factors that predict for
      biochemical-free survival (bNED) control and present the bNED control rates.
      METHODS AND MATERIALS: Between May 1, 1990 and November 30, 1994, 160 patients
      with nonpalpable PSA-detected prostate cancer received 3DCRT at Fox Chase Cancer
      Center (median total dose 73 Gy; range: 67-78 Gy). bNED failure was defined as
      three consecutive increases in posttreatment PSA after achieving a nadir. bNED
      failure was recorded as the time midway between the nadir and the first
      consecutive rising PSA. Five-year actuarial rates of bNED control were calculated
      for pretreatment PSA (0-9.9 vs. 10-19.9 vs. > or = 20 ng/ml), Gleason score (2-6
      vs. 7-10), treatment field size (prostate vs. small pelvis), age (<65 vs. > or =
      65), and dose (< or = 73 vs. >73 Gy) using Kaplan-Meier methods and compared
      using the Log rank test. The Cox model was used to multivariately establish
      independent predictors based on significant univariate factors. Median follow-up
      was 39 months (range: 2-84 months). RESULTS: The 5-year actuarial rate of bNED
      control was 86% for the entire group of patients. The Cox Proportional Hazards
      model demonstrated that pretreatment PSA was an independent predictor of bNED
      control. Treatment field size was marginally predictive. There was no difference
      in bNED control when patients were stratified by the number of lobes positive for
      disease. Statistically different rates of bNED control were seen when the
      patients with nonpalpable disease were univariately compared to T2b and T2c
      patients. Three patients experienced Grade 3-4 genitourinary (GU) toxicity and 3
      patients experienced Grade 3-4 gastrointestinal (GI) toxicity. CONCLUSIONS:
      Patients with nonpalpable PSA-detected prostate cancer can be effectively treated
      with 3DCRT with minimal morbidity and high rates of bNED control at 5 years.
      Pretreatment PSA level is an independent predictor of bNED control.

PMID- 9635698
TI  - High dose-rate afterloading 192Iridium prostate brachytherapy: feasibility
      report.
AB  - BACKGROUND: RESULTS from localized prostate cancer series using seed implants
      have been most encouraging. However, with current techniques, inadequate
      dosimetry sometimes occurs. Remote afterloading high dose rate 192Iridium
      brachytherapy (HDR-Ir192) theoretically remedies some potential inadequacies of
      seed implantation by performing the dosimetry after the needles are in place.
      This study was undertaken to determine the feasibility of incorporating
      multifractionated HDR-Ir192 in the brachytherapy management of prostate
      carcinoma. METHODS: From October 1989 to August 1995, 104 patients were treated
      with a combination of multifractionated HDR-Ir192 and external beam. Patients
      ranged in age from 48-78 years, with a mean of 68.6 years. By TNM clinical stage,
      there were 1 T1b, 31 T1c, 28 T2a, 24 T2b, 9 T2c, 8 T3a, and 3 T3c lesions. For
      the group, the mean initial pretreatment PSA was 12.9 ng/ml (median 8.1), with
      90% of the patients having had a pretreatment PSA greater than a normal value of
      4.0 ng/ml. Patients with prostate volumes up to 105 cc were implanted. Treatment
      was initiated with perineal needle placement using ultrasound guidance. A
      postoperative CT scan was obtained to provide the basis for treatment planning.
      Four HDR-Ir192 treatments were given over a 40-h period, with a minimal
      peripheral dose (MPD) ranging from 3.00 to 4.00 Gy per fraction over the course
      of this study. Two weeks later, external beam radiation was added using 28
      fractions of 1.80 Gy daily, to a dose of 50.40 Gy. RESULTS: Follow-up ranged from
      10 to 89 months, with a mean of 46 months and median of 45 months. At various
      follow-up points, the patient numbers at risk were: 1 year, 101; 3 years, 69; 5
      years, 28. The technique proved to be uniformly applicable to a wide range of
      prostate volumes and was very well tolerated by patients. Nearly all significant
      late in-field treatment complications were genitourinary in nature. Of the
      patients, 6.7% developed urethral strictures that were readily manageable.
      Changes in technique implemented in 1993 appear to have significantly lessened
      the incidence of this complication. Two patients developed significant uropathy
      within the first treatment year, but both resolved; 1 of these 2 patients had a
      prior TURP. Other bladder or rectal complications have been minimal. Using PSA
      progression as a marker of tumor response, approximately 84% of patients whose
      initial PSA was less than 20 ng/ml were free of progression at 5 years by
      actuarial analysis. CONCLUSIONS: We found the use of transperineal
      ultrasonography, postimplant CT-based dosimetry, coupled with adjustable dose
      delivery inherent to remote afterloading technology, to give unparalleled control
      in performing this complex brachytherapy task. Thus, it may be advantageous in
      certain clinical situations where the resultant MPD is needed to reliably cover
      the target volume, such as in patients with carcinomas at base locales, when the
      possibility of moderate to extensive intraprostatic tumor exists, and in patients
      with large glands. Early PSA data suggest that it may be effective as a
      definitive treatment with rates of adverse late tissue effects that are
      acceptable using current technique and doses described herein. Longer follow-up
      is needed to ascertain its position among the various treatment regimens for
      prostate carcinoma.

PMID- 9635699
TI  - Carcinoma of the urethra in women.
AB  - PURPOSE: This analysis was performed to evaluate the influence of clinical and
      treatment factors on local tumor control, survival, and complications for women
      with urethral carcinoma. METHODS AND MATERIALS: The records of 44 women with
      carcinoma of the urethra were reviewed. Their age ranged from 37 to 89 years
      (mean, 67 years). Mean follow-up time was 8.25 years. The stages of disease were
      T1 in eight, T2 in five, T3 in 22, and T4 in nine. Treatment was with surgery in
      7, radiotherapy in 25, and combined surgery and radiotherapy in 12. RESULTS: The
      5-year overall survival was 42% and the 5-year cause-specific survival was 40%.
      At the time of last follow-up, 11 women were alive and 33 were dead. Recurrence
      of tumor occurred in 27 women and was the cause of death for 23. Recurrence was
      local in 8, local and distant in 15, and distant in 4. Severe complications
      occurred in nine women (20%). The severe complication rate was 29% (2 of 7) for
      women treated with surgery, 24% (6 of 25) for women treated with radiotherapy,
      and 8% (1 of 12) for women treated with surgery and radiotherapy. A multivariate
      analysis was performed to evaluate the interaction of tumor size, histology, and
      location, and lymph node status. This analysis indicated that tumor size and
      histology were independent prognostic factors for survival and local tumor
      control. Adenocarcinoma occurred in 13 women, and none of them were alive at 5
      years. Only 1 of 10 women with tumors greater than 4 cm was alive at 5 years.
      CONCLUSIONS: The most significant clinical factors affecting prognosis were tumor
      size and histology. Tumor location was not an independent prognostic variable.
      None of the women with adenocarcinoma, and only one woman with a tumor greater
      than 4 cm was alive at 5 years, irrespective of modality of treatment. Aggressive
      treatment resulted in a high complication rate.

PMID- 9635700
TI  - A randomized study of two doses of abdominopelvic radiation therapy for patients
      with optimally debulked Stage I, II, and III ovarian cancer.
AB  - PURPOSE: To determine whether an increased dose of abdominal radiation therapy
      results in improved disease control and survival in patients with early ovarian
      cancer. METHODS AND PATIENTS: Between 1981 and 1990, 125 patients with optimally
      debulked Stage I, II, and III ovarian cancer were entered into a prospective
      randomized clinical trial of abdominopelvic radiation therapy. Patients were
      stratified and randomized to either the control arm, treated with an abdominal
      dose of 22.5 Gy in 22 fractions, or the experimental arm of 27.5 Gy in 27
      fractions. A pelvic boost dose of 22.5 Gy was used in both arms. There were 43
      patients with Stage I tumors, 71 Stage II tumors, and 11 Stage III tumors.
      Nineteen patients had grade 1 histology, 77 grade 2, and 29 grade 3. Three
      patients had small-volume residual disease (<2 cm) in the pelvis alone and the
      remainder had no gross tumor following surgery. Median follow-up was 6.6 years
      (range 1.4-9.9). RESULTS: Overall survival (OS) at 5 years was 83% in the low
      dose arm and 72% in the high-dose arm (p = 0.3). Disease-free survival (DFS) at 5
      years was 74% and 67% in the low-dose and high-dose arms, respectively (p = 0.5).
      The difference in OS between the two arms was -11%, with 95% confidence intervals
      of -26% (favoring low-dose treatment) to 4% (in favor of high dose). The
      difference in DFS was -7% (95% confidence interval, -23 to 9%). Failure in the
      pelvis alone predominated (n = 15); six patients had abdominal and pelvic failure
      and seven patients failed in the abdomen alone. There were no differences in
      patterns of relapse, hematologic toxicity, or late complications between the two
      arms. Serious bowel toxicity was seen in three patients: two in the low-dose and
      one in the high-dose arm. A Cox proportional hazards model was used to assess the
      effect of treatment when adjusting for other prognostic variables. Ascites (p =
      0.03, relative risk 2.05) was the only significant covariate in predicting
      disease-free survival, but was not prognostic for overall survival. CONCLUSIONS:
      There was no difference in survival, tumor control, or toxicity between high-dose
      and low-dose abdominopelvic radiation therapy. High-dose abdominopelvic radiation
      therapy is unlikely to be associated with an increase in OS of more than 4% or
      DFS of more than 9%.

PMID- 9635701
TI  - Preoperative radiotherapy and surgery for endometrial carcinoma: prognostic
      significance of the sterilization of the specimen.
AB  - INTRODUCTION: We report a retrospective study on the analysis of the operative
      specimen after preoperative radiotherapy for FIGO (1971) stage I or II
      endometrial carcinoma. METHODS AND MATERIALS: From 1976 to 1996, 221 patients
      were treated with external radiotherapy (XRT) and/or low-dose-rate brachytherapy
      (BT) followed by surgery (S). Patients with cervical involvement (89 patients) or
      with high-grade tumors (49 patients) received XRT and BT. Patients stage FIGO Ia
      (89 patients) or with low-grade tumors (57 patients) received BT alone. Surgery
      was performed 5 to 6 weeks after irradiation. RESULTS: The mean follow-up is 78
      months (12-216). The 5-year survival was 90% for FIGO Ia, 80% for FIGO Ib, and
      84% for FIGO II (p = 0.51). According to the differentiation, 5-year survival was
      87% for grade 1, 84% for grade 2, 84% for grade 3 (p = 0.10). Grade 3
      complications were registered in 2% (no grade 4). The tumors were sterilized in
      37 patients (17%), sterilized but with dystrophic glands in 34 patients (16%),
      only modified and altered in 21 patients (9.5%), with viable cells in 56 patients
      (26%). After preoperative radiotherapy, 37/148 specimens were sterilized (25%),
      14/74 after brachytherapy and surgery (19%), 23/74 after external radiotherapy
      brachytherapy and surgery (31%). According to the response of the specimen, 5
      year survival was 87% when the tumor was sterilized, 96% when altered glands were
      present, 85% when modified, and 76% if residual tumor with viable cells was
      identified (p = 0.043). CONCLUSION: Preoperative radiotherapy followed by surgery
      is a safe and effective treatment of FIGO stage I or II endometrial carcinomas.
      BT with two uterine tubes seems to be of interest in the contribution of the
      treatment of the uterus to sterilize the specimen. The analysis of this new
      prognostic factor remains important to select a population with worst prognosis.

PMID- 9635702
TI  - Comprehensive irradiation of head and neck cancer using conformal multisegmental
      fields: assessment of target coverage and noninvolved tissue sparing.
AB  - PURPOSE: Conformal treatment using static multisegmental intensity modulation was
      developed for patients requiring comprehensive irradiation for head and neck
      cancer. The major aim is sparing major salivary gland function while adequately
      treating the targets. To assess the adequacy of the conformal plans regarding
      target coverage and dose homogeneity, they were compared with standard
      irradiation plans. METHODS AND MATERIALS: Fifteen patients with stage III/IV head
      and neck cancer requiring comprehensive, bilateral neck irradiation participated
      in this study. CT-based treatment plans included five to six nonopposed fields,
      each having two to four in-field segments. Fields and segments were devised using
      beam's eye views of the planning target volumes (PTVs), noninvolved organs, and
      isodose surfaces, to achieve homogeneous dose distribution that encompassed the
      targets and spared major salivary gland tissue. For comparison, standard three
      field radiation plans were devised retrospectively for each patient, with the
      same CT-derived targets used for the clinical (conformal) plans. Saliva flow
      rates from each major salivary gland were measured before and periodically after
      treatment. RESULTS: On average, the minimal dose to the primary PTVs in the
      conformal plans [95.2% of the prescribed dose, standard deviation (SD) 4%] was
      higher than in the standard plans (91%, SD 7%; p = 0.02), and target volumes
      receiving <95% or <90% of the prescribed dose were smaller in the conformal plans
      (p = 0.004 and 0.02, respectively). Similar advantages of the conformal plans
      compared to standard plans were found in ipsilateral jugular nodes PTV coverage.
      The reason for underdosing in the standard treatment plans was primarily failure
      of electron beams to fully encompass targets. No significant differences were
      found in contralateral jugular or posterior neck nodes coverage. The minimal dose
      to the retropharyngeal nodes was higher in the standard plans. However, all
      conformal plans achieved the planning goal of delivering 50 Gy to these nodes. In
      the conformal plans, the magnitude and volumes of high doses in noninvolved
      tissue were significantly reduced. The main reasons for hot spots in the standard
      plans (whose dose calculations included missing tissue compensators) were
      photon/electron match line inhomogeneities, which were avoided in the conformal
      plans. The mean doses to all the major salivary glands, notably the contralateral
      parotid (receiving on average 32% of the prescribed dose, SD 7%) were
      significantly lower in the conformal plans compared with standard radiation
      plans. The mean dose to the noninvolved oral cavity tended to be lower in the
      conformal plans (p = 0.07). One to 3 months after radiation, on average 60% (SD
      49%) of the preradiation saliva flow rate was retained in the contralateral
      parotid glands and 10% (SD 16%) was retained in the submandibular/sublingual
      glands. CONCLUSIONS: Planning and delivery of comprehensive irradiation for head
      and neck cancer using static, multisegmental intensity modulation are feasible.
      Target coverage has not been compromised and dose distributions in noninvolved
      tissue are favorable compared with standard radiation. Substantial major salivary
      gland function can be retained.

PMID- 9635703
TI  - Parathyroid carcinoma--the Princess Margaret Hospital experience.
AB  - PURPOSE: Carcinoma of the parathyroid gland is a rare disease representing 0.5 to
      4% of patients with primary hyperparathyroidism. We reviewed our experience with
      this disease, with special emphasis on the role of adjuvant postoperative
      radiotherapy. METHODS: A retrospective review was conducted of all cases of
      parathyroid carcinoma referred to the Princess Margaret Hospital (PMH) from 1958
      1996. Ten patients were identified. Their clinical features, management details,
      and treatment outcome are described. RESULTS: There were 5 men and 5 women with a
      mean age of 53 years. Of these, 7 patients underwent en bloc resection; among
      them, 4 had neck dissection or lymph node sampling. The other 3 patients
      underwent only limited surgery to remove the tumor. Seven patients were referred
      for consideration of adjuvant radiation treatment. Six patients were given
      adjuvant radiation therapy for microscopic residual disease. All patients
      tolerated the radiation treatment well, with minimal side effects. The 7 patients
      have been followed regularly with no evidence of recurrence and normal serum
      calcium. The mean follow-up for the 6 patients who had adjuvant radiotherapy was
      62.3 months (range 12 to 156 months). The remaining 3 patients had metastatic
      disease and were referred for palliative radiotherapy. CONCLUSIONS: Our results
      in a small number of patients suggest local radiation therapy to the tumor bed
      may have eliminated the strong predilection for local recurrence of this disease,
      as reported by other investigators.

PMID- 9635704
TI  - Prognostic significance of DNA content in stage I adenocarcinoma of the lung.
AB  - PURPOSE: Up to 30% of lung cancers (Stage I) with the most favorable outcome
      recur within 5 years after surgery. This study reviews the pattern of failure
      after surgical resection in early lung cancers and determines whether flow
      cytometric DNA variables were prognostic indicators for survival, disease-free
      survival (DFS), or distant metastasis-free survival (DMFS). METHODS AND
      MATERIALS: Pathologic specimens from 45 patients at The University of Texas M. D.
      Anderson Cancer Center who underwent surgical resection and mediastinal nodal
      dissection for stage I (AJCC) adenocarcinomas of the lung were analyzed by flow
      cytometry for DNA content. Survival was calculated by the method of Desu and Lee.
      Chi-square and cross tabulation were used in the analysis. RESULTS: The mean age
      of the patients was 62 years, and 52.3% were male. All patients were clinical
      Stage I (T1-2 N0), Karnofsky performance status > or = 70, and had a weight loss
      <10 lbs. Median overall survival (OS) and DFS were 50 months and 33 months,
      respectively. OS, DFS, and DMFS at 1, 3 and 5 years were 73%, 57%, and 35%; 63%,
      53%, and 45%; and 67%, 56%, and 48%, respectively. Analysis of all 45 patients
      revealed 86% of patients developing brain metastasis had an abnormal DNA content
      > or = 30%, whereas 4% of patients with brain metastasis had abnormal DNA content
      < 30% (p = 0.01). This correlation maintained significance when only pT1/2
      lesions were analyzed. There was a significant statistical correlation between
      abnormal DNA and 5-year OS, with 74% OS for those with abnormal DNA < 30% vs. 42%
      for > or = 30% (p = 0.036). The 5-year DFS for pT1/2 patients was significantly
      correlated with abnormal DNA content: 53% for patients with abnormal DNA < 30%
      vs. 17% for patients with abnormal DNA > or = 30%, respectively (p = 0.03). Of
      those with %S fraction (%S) < 2, 13% failed locally compared to 41% of those with
      %S > or = 2. There was a highly significant correlation between DNA index (DNAI)
      and aneuploid %S: 68% of patients with a DNAI > or = 1.7 had > or = 2.6 aneuploid
      %S, whereas only 13% of patients with DNAI > or = 1.7 had aneuploid %S < 2.6. (p
      < 0.001). Grouping the percent of abnormal DNA and overall %S according to low
      vs. mixed vs. high values correlated with DFS (p = 0.02). CONCLUSIONS: This study
      confirms significant correlation between a high DNA index and a higher frequency
      of brain metastasis, as well as worse OS. Although DNA content variables were not
      predictive of recurrence at other sites, brain metastasis represents the worst
      outcome from distant metastasis. Further studies are needed, as well as
      prospective trials, for evaluating adjuvant therapy in patients with adverse DNA
      variables following complete surgical resection for early disease. If high-risk
      patients could be identified after resection, adjuvant therapy (chemotherapy or
      elective brain irradiation) could be administered.

PMID- 9635705
TI  - Preoperative radiotherapy in esophageal carcinoma: a meta-analysis using
      individual patient data (Oesophageal Cancer Collaborative Group).
AB  - PURPOSE: The existing randomized evidence has failed to conclusively demonstrate
      the benefit or otherwise of preoperative radiotherapy in treating patients with
      potentially resectable esophageal carcinoma. This meta-analysis aimed to assess
      whether there is benefit from adding radiotherapy prior to surgery. METHODS AND
      MATERIALS: This quantitative meta-analysis included updated individual patient
      data from all properly randomized trials (published or unpublished) comprising
      1147 patients (971 deaths) from five randomized trials. RESULTS: With a median
      follow-up of 9 years, the hazard ratio (HR) of 0.89 (95% CI 0.78-1.01) suggests
      an overall reduction in the risk of death of 11% and an absolute survival benefit
      of 3% at 2 years and 4% at 5 years. This result is not conventionally
      statistically significant (p = 0.062). No clear differences in the size of the
      effect by sex, age, or tumor location were apparent. CONCLUSION: Based on
      existing trials, there was no clear evidence that preoperative radiotherapy
      improves the survival of patients with potentially resectable esophageal cancer.
      These results indicate that if such preoperative radiotherapy regimens do improve
      survival, then the effect is likely to be modest with an absolute improvement in
      survival of around 3 to 4%. Trials or a meta-analysis of around 2000 patients
      would be needed to reliably detect such an improvement (15-->20%).

PMID- 9635706
TI  - Apoptosis, proliferation, bax, bcl-2 and p53 status prior to and after
      preoperative radiochemotherapy for locally advanced rectal cancer.
AB  - PURPOSE: To investigate the relationship between apoptotic cell death,
      proliferative activity, and the expression of apoptosis regulating proteins in
      rectal cancer prior to and after radiochemotherapy. MATERIALS AND METHODS: In 32
      patients dispositioned to receive preoperative radiochemotherapy for locally
      advanced rectal carcinoma, pretherapy biopsies and the final resected specimen
      after radiochemotherapy were available for analyses. Apoptotic cells were
      identified and quantified using in situ end labeling (ISEL) technique. The
      expression of the bax protein was assessed immunohistochemically. Additionally,
      double immunostaining was performed for apoptotic cells and bax expression. The
      proliferative activity was determined by immunohistochemical assessment of the
      Ki67 (MIB-1) and the proliferating cell nuclear antigen (PCNA). p53- and bcl-2
      expression was analyzed immunohistochemically. A clinical-to-pathologic
      downstaging after radiochemotherapy was achieved in 25 of 32 patients (78%).
      During follow-up, tumor recurrence was observed in six cases. In one case, no
      residual tumor was detected after radiochemotherapy. RESULTS: After
      radiochemotherapy, the apoptotic index increased significantly in almost every
      case examined. In contrast, the proliferative activity was significantly
      decreased in resected specimens as compared to biopsies. Bax immunostaining was
      detected in 12/31 (39%) biopsies and in 26/31 (84%) resected specimens. In the
      resected specimen, significantly more apoptotic cells that were bax-positive were
      found than in biopsies. Bcl-2 immunostaining occurred in 15/31 biopsies and 12/31
      resected specimens, respectively. Tumors that were immunohistochemically negative
      for p53 (20/31 [65%]) generally exhibited a higher apoptotic index and a high
      expression level of bax than p53-positive tumors (11/31 [35%]). However, we did
      not find any correlation between the (pre- and post-therapeutic) rate of
      apoptosis or the level of bax expression and the degree of clinical-to-pathologic
      downstaging or the frequency of tumor recurrence. CONCLUSION: Our results
      indicate that radiochemotherapy is associated with an increase in bax expression
      and also in apoptotic cell death. The observation of higher rates of apoptosis
      and bax in p53-negative tumors suggests that p53 might be a possible regulating
      factor of apoptosis in rectal cancer.

PMID- 9635707
TI  - Acute treatment-related diarrhea during postoperative adjuvant therapy for high
      risk rectal carcinoma.
AB  - PURPOSE: The combination of pelvic radiotherapy and 5-fluorouracil-based
      chemotherapy is associated with an increase in acute gastrointestinal toxicity
      during rectal adjuvant therapy, most notably an increased incidence of diarrhea.
      Previous randomized, prospective studies have limited their analysis to
      presenting rates of severe and life-threatening diarrhea (Grade 3 or greater),
      and few data are available detailing the extent of mild to moderate diarrhea. To
      provide baseline data for future studies, we conducted a detailed analysis of
      diarrhea from a prior clinical trial of adjuvant therapy for rectal cancer.
      METHODS AND MATERIALS: In a multiinstitutional clinical trial, 204 eligible
      patients with rectal carcinoma that either was deeply invasive (T3-T4) or
      involved regional lymph nodes were randomized to receive either postoperative
      pelvic radiotherapy alone (45 to 50.4 Gy) or pelvic radiotherapy and bolus 5
      fluorouracil-based chemotherapy. Toxicity was assessed prospectively. RESULTS:
      For the 99 eligible patients who received pelvic radiotherapy alone, rates of
      Grades 0, 1, 2, 3, and 4 diarrhea during treatment were 59, 20, 17, 4, and 0%,
      respectively. For the 96 eligible patients who received radiotherapy and 5
      fluorouracil, the overall rates of grades 0, 1, 2, 3, and 4 diarrhea were 21, 34,
      23, 20, and 2%, respectively. The increased rates of diarrhea during adjuvant
      rectal therapy were manifested across all toxicity levels for patients receiving
      chemotherapy and pelvic radiotherapy. Of primary clinical importance is the
      substantial increase in severe or life-threatening diarrhea (Grade 3 or more) (22
      vs. 4%,p = 0.001) Additionally, increased rates of any diarrhea and also severe
      or life-threatening diarrhea were observed in patients who had a low anterior
      resection compared with those who had an abdominoperineal resection (p < 0.001
      and p = 0.006, respectively). CONCLUSION: These results will be of value as a
      baseline for investigators who want to use treatment toxicity as an end point in
      cancer control or cancer therapy trials utilizing similar treatment techniques.
      Patients receiving 5-fluorouracil and pelvic radiotherapy compared with patients
      receiving pelvic radiotherapy alone and patients with a prior history of a low
      anterior resection compared with patients who had a prior history of an
      abdominoperineal resection experienced increased rates of Grades 1 through 4
      acute treatment-related diarrhea, and the most important increase occurred as
      Grade 3 toxicity.

PMID- 9635708
TI  - A close or positive margin after mastectomy is not an indication for chest wall
      irradiation except in women aged fifty or younger.
AB  - INTRODUCTION: Indications for postmastectomy radiation include primary tumor size
      > or = 5 cm and/or > or = 4 positive axillary nodes. In clinical practice,
      patients with a close or positive margin after mastectomy are also often treated
      with postmastectomy radiation. However, there is little data regarding the risk
      of a chest wall recurrence in patients with close or positive margins who
      otherwise would be considered low risk (tumor size <5 cm and/or 0-3 positive
      nodes). To address this issue, we assessed the risk of a chest wall recurrence in
      women with Stage I-II breast cancer who underwent mastectomy and were found to
      have primary tumor size <5 cm and 0-3 positive nodes with a close or positive
      deep margin. METHODS AND MATERIALS: The pathologic reports from 789 patients
      treated by mastectomy between 1985 and 1994 at our institution were
      retrospectively reviewed. Of these, 136 (17%) had tumor within 1 cm of the deep
      resection margin. The study population consists of 34 of these patients with
      close or positive margins whose primary tumor size was <5 cm with 0-3 positive
      axillary nodes and who received no postoperative radiation. The median age was 43
      years (range 29-76). Of these, 44% had T1 tumors and 56% T2 tumors. Pathologic
      axillary nodal status was negative in 65% and positive in 35%. The median number
      of positive nodes was 1. The deep margin was positive in 2 patients, < or = 2 mm
      in 17 patients, 2.1-4 mm in 7 patients and 4.1-6 mm in 8 patients. Of the 34
      patients, 67% received adjuvant chemotherapy +/- tamoxifen and 21% received
      tamoxifen alone. The median follow-up was 59 months (range 7-143). RESULTS: There
      were 5 chest wall recurrences at a median interval of 26 months (range 7-127).
      One was an isolated first failure, one occurred concurrent with an axillary
      recurrence, and three were associated with distant metastases. The 5- and 8-year
      cumulative incidences of a chest wall recurrence were 9% and 18%. Patient age
      correlated with the cumulative incidence of chest wall recurrence at 8 years; age
      < or = 50 years had a rate of 28% vs. 0% for age >50 (p = 0.04). There was no
      correlation with chest wall failure and number of positive nodes, ER status,
      lymphovascular invasion, location of primary, grade, family history, or type of
      tumor close to the margin. Of 5 chest wall failures, 4 were in patients who had
      received adjuvant systemic chemotherapy +/- tamoxifen. Chest wall failures
      occurred in 1 patient with a positive deep margin, 3 patients with margins within
      2 mm, and 1 patient with a margin of 5 mm. The estimated cumulative incidence
      probability of chest wall recurrence at 8 years by margin proximity was 24% < or
      = 2 mm vs. 7% 2.1-6 mm (p = 0.36), and by clinical size 24% for T2 tumors vs. 7%
      for T1 (p = 0.98). CONCLUSIONS: A close or positive margin is uncommon (< or =
      5%) after mastectomy in patients with tumor size <5 cm and 0-3 positive axillary
      nodes but, when present, it appears to be in a younger patient population. The
      subgroup of patients aged 50 or younger with clinical T1-T2 tumor size and 0-3
      positive nodes who have a close (< or = 5 mm) or positive mastectomy margin are
      at high risk (28% at 8 years) for chest wall recurrence regardless of adjuvant
      systemic therapy and, therefore, should be considered for postmastectomy
      radiation.

PMID- 9635709
TI  - Diagnostic thoracic-computed tomography in radiotherapy for loco-regional
      recurrent breast carcinoma.
AB  - PURPOSE: This study was initiated to evaluate whether pretreatment diagnostic
      thoracic CT scan was useful for patients with loco-regional recurrent breast
      carcinoma, and to assess its impact on the design of radiotherapeutic treatment.
      METHODS AND MATERIALS: Between March 1991 and January 1997, 44 patients underwent
      thoracic CT examination with contrast material before the consideration of
      radiotherapy for their isolated loco-regional recurrent breast carcinoma. The CT
      radiographs were prospectively reviewed for additional findings clinically
      undetected by prior physical examination and plain-chest radiograph. The changes
      made in treatment design and dosage of radiation as a result of CT findings were
      recorded for analysis. The correlation between prognostic indicators and the CT
      findings was also studied. RESULTS: Twenty-two of 44 (50%) patients were found to
      have additional abnormalities detected only after thoracic CT examinations were
      performed. The strategy of radiation therapy was altered in 17 of 22 (77%)
      patients as a result. Patients with shorter disease-free interval (p = 0.08) and
      multiple sites of recurrence (p = 0.05) tended to have greater numbers of
      findings on CT scan previously unsuspected. Thus, CT scan is a valuable guide to
      treating loco-regional recurrent disease. CONCLUSION: Pretreatment diagnostic
      thoracic CT scan offers essential information that can alter treatment planning
      and thus optimize treatment strategy for a large proportion of patients with
      clinically isolated loco-regional recurrent breast carcinoma. In this population
      of patients we recommend that thoracic CT examination be considered before the
      initiation of radiation therapy.

PMID- 9635710
TI  - Primary central nervous system lymphoma: age and performance status are more
      important than treatment modality.
AB  - PURPOSE: To assess prognostic factors and treatment modalities of patients with
      primary central nervous system lymphoma (PCNSL) in terms of response rates,
      patterns of failure and overall survival. METHODS AND MATERIALS: Sixty-two
      patients presenting with PCNSL between 1982 and 1994 at Peter MacCallum Cancer
      Institute with no evidence of human immunodeficiency virus infection were
      included in the study. Their median age was 60 years; World Health Organisation
      (WHO) performance status was > or = 2 in 85%. All patients were planned to
      receive whole brain irradiation; 7 also received spinal irradiation. The median
      planned dose to the target volume was 50.4 Gy. Twenty patients were planned to
      receive chemotherapy as well. Patients were followed up to June 20, 1995, giving
      a median follow-up for 14 surviving patients of 5.4 years, range 0.3 to 10.2
      years. RESULTS: The clinical response rate to treatment was 77% [95% confidence
      interval (CI) 65 to 87%]. The estimated median overall survival was 20.6 months
      (CI 12.4 to 33.4 months). On univariate analysis male gender, age <60 years, WHO
      performance status < or = 1, treatment to the target volume > or = 45 Gy, and
      treatment with additional chemotherapy, were associated with a significantly
      better overall survival (p < 0.05). On multivariate analysis only age and
      performance status remained significant prognostic variables. Relapse involved
      the central nervous system or cerebrospinal fluid (CSF) in all patients with
      known sites of relapse except three who had ocular relapse only. There was a low
      incidence of relapse in the initial brain site (23% of known cases) and a high
      incidence (50%) of CSF/spinal cord relapse. Of 48 deaths, 15 were related to
      initial or subsequent treatment. CONCLUSIONS: Patient outcome is strongly
      influenced by age and performance status. Studies suggesting better survival for
      patients treated with chemoradiation may reflect patient selection rather than
      treatment variables. Optimal management remains to be defined. The high
      CSF/spinal relapse rate deserves particular attention.

PMID- 9635711
TI  - Determination of the inferior border of the thecal sac using magnetic resonance
      imaging: implications on radiation therapy treatment planning.
AB  - PURPOSE: To determine whether the traditional teaching of placing the caudal
      border of the spinal field at the S2-S3 interspace in children receiving
      craniospinal irradiation (CSI) is appropriate. METHODS AND MATERIALS: Twenty
      three children had magnetic resonance imaging (MRI) of the spine with gadolinium
      prior to craniospinal irradiation at one institution. Thecal sac termination
      using MRI was determined by drawing a perpendicular line from the point of
      convergence of dural margins to the corresponding vertebral body. RESULTS:
      Location of thecal sac termination varied from mid-S1 to low S3 vertebral body,
      with the most frequent site at the upper S2 vertebral level. Only 2 of 23 (8.7%)
      children had thecal sac terminations below the S2-S3 interspace. For the nine
      patients with neuraxis disease, none had thecal sac terminations below the S2-S3
      interspace. In seven of the nine patients who had neuraxis seeding at initial
      presentation, MRI of the spine after CSI was performed and showed that thecal sac
      termination was lower after radiation therapy in two children, higher in one, and
      the same in four. CONCLUSIONS: In 2 of 23 children (8.7%), placement of the
      inferior border at the bottom of the S2 vertebral body would have missed the
      entire thecal sac. Treatment to the entire neuraxis with adequate coverage of
      distal spinal theca can be achieved by using MRI. Individualized spinal fields
      using the MRI may help minimize radiation scatter to the gonads while adequately
      covering the target volume.

PMID- 9635712
TI  - Defining the superior border of posterior fossa radiation treatment fields.
AB  - PURPOSE: Lateral posterior fossa treatment fields are usually defined on
      traditional simulation films based on bony landmarks. The superior field border,
      intended to include the apex of the tentorium cerebelli, is frequently difficult
      to define. While sagittal magnetic resonance imaging (MRI) images or three
      dimensional treatment planning tools are good means to locate the tentorial apex,
      these are not always available. We herein describe a method for locating the
      tentorial apex based on bony landmarks. METHODS AND MATERIALS: Midsagittal
      magnetic resonance images of 53 patients were reviewed. Using a Cartesian grid,
      the geometric relationship between the tentorial apex and several bony landmarks
      was assessed. Two lines were defined: the first connected the posterior clinoid
      and the internal occipital protuberance (AB). The second was perpendicular to the
      first, included the tentorial apex, and extended from the base of the skull
      inferiorly to the "crown" of the skull superiorly (DE). Relationships between
      measurements were made using linear regression and least square fits. RESULTS:
      Line DE was within 5 mm of the perpendicular bisector of line AB in 83% (44/53)
      of patients. The tentorial apex was located within 10 mm of the midpoint of DE in
      91% (48/53) of patients. CONCLUSION: In the majority of patients, the location of
      the tentorial apex can be estimated based on bony landmarks, to within
      approximately 10 mm. The technique described is a useful means of estimating the
      location of the tentorial apex in patients where sagittal MRI imaging or three
      dimensional treatment planning tools are not available.

PMID- 9635714
TI  - Augmented therapy of extensive Hodgkin's disease: radiation to known disease or
      prolongation of induction chemotherapy did not improve survival--results of a
      Cancer and Leukemia Group B study.
AB  - PURPOSE: This prospective randomized trial in extensive untreated Hodgkin's
      disease was undertaken to assess the potential benefit of augmented therapy (12
      months chemotherapy or radiation to known disease) compared to standard 6 months
      chemotherapy. PATIENT AND METHODS: A total of 258 patients, mostly Stage IV, were
      randomized to four treatment regimens consisting of six cycles of CCNU,
      vinblastine, procarbazine, and prednisone (CVPP); 12 cycles of CVPP; six cycles
      of CVPP followed by 25 Gy radiotherapy; or three cycles CVPP, 25 Gy radiotherapy,
      and three cycles CVPP. RESULTS: Complete remissions were achieved in 65% of all
      patients. A 58% overall 5-year survival rate was obtained. Relapses in irradiated
      areas of known disease occurred in only 6% of responding patients. There was,
      however, no statistical difference in response frequency, disease-free survival,
      or overall survival among the four regimens. Elderly patients responded less
      frequently. CONCLUSION: While radiotherapy provided control of local (known)
      disease, no impact on overall survival was apparent. Likewise, doubling the
      duration of chemotherapy did not improve response or survival. Augmentation of
      therapy with either radiotherapy or more chemotherapy in this study was of no
      benefit compared to the standard 6 months of treatment.

PMID- 9635713
TI  - Disposition and tissue distribution of boron after infusion of borocaptate sodium
      in patients with malignant brain tumors.
AB  - PURPOSE: In the frame of the Czech boron neutron capture therapy (BNCT) project,
      a clinical Phase I study of borocaptate sodium [Na2B12H11SH (BSH)] as the boron
      10 delivery agent was performed to obtain data on disposition and tissue
      distribution of boron after an infusion of this compound, as well as to establish
      an optimal protocol for BNCT of malignant cerebral tumors. METHODS AND MATERIALS:
      The kinetics of boron disposition after an infusion of borocaptate sodium (25
      mg/kg body wt over the period of 1 h) was studied in a group of 10 patients with
      astrocytoma or glioblastoma of cerebral hemispheres using a modification of the
      Soloway-Messer colorimetric method. The boron content of tissues (tumor, healthy
      brain, dura mater, muscle, skin, and cranial bone) removed during the operation
      performed with latencies varying between 3 and 18 h was investigated by atomic
      emission spectrometry. RESULTS: Compartmental analysis of boron blood
      concentrations has shown that in the majority of patients (four males and three
      females), the concentration decline can be adequately described by a two
      compartment pharmacokinetic model (i.e., by a biexponential relationship). The
      calculated half-lives of the initial (fast) phase of the concentration decline
      varied between 0.85 and 3.65 h, whereas the half-life values for the terminal
      (slow) phase ranged between 22.2 and 111.8 h. However, in the remaining three
      patients (all females), the goodness of fit of the boron concentration data was
      significantly better when a pharmacokinetic model with three compartments was
      assumed. In these patients, therefore, an additional ultrafast phase with a half
      life varying between 17 and 37 min was detected in the beginning of the boron
      blood concentration decline. On the other hand, in one of these patients, the
      half-life of the terminal phase was found to be 415 h (i.e., more than 17 days).
      Such a long persistence in the body is explained by the very high value of the
      total distribution volume, indicating extensive binding of BSH in peripheral
      tissues. Another reason may be enterohepatic recycling of BSH. CONCLUSION: Tumor
      to-blood ratios higher than 1.5, which are necessary for an effective outcome of
      BNCT, can be obtained only if the time interval elapsing between the onset of
      surgery and termination of BSH infusion is at least 12 h.

PMID- 9635715
TI  - Outcomes of high-dose unilateral kidney irradiation in patients with gastric
      lymphoma.
AB  - PURPOSE: To review the long-term clinical effects of unilateral kidney
      irradiation on overall renal function and blood pressure in patients with gastric
      lymphoma. METHODS AND MATERIALS: In the study were 27 patients with Stage I or II
      gastric lymphoma who had undergone irradiation of at least 24 Gy to > or = 1/3 of
      the left kidney. They include 16 women and 11 men, aged 31 to 77, with a mean age
      of 57.6 years (median 56). Fifteen patients had Stage I and 12 had Stage II
      disease. In 13 patients the whole kidney had been irradiated, and 14 had had
      partial kidney irradiation, at doses ranging between 24 and 40.5 Gy. All patients
      received combined chemotherapy with various drugs: all patients received
      corticosteroids, and five received cis-platinum. Their follow-up ranged between
      0.7 and 7.8 years (mean 3.4 years). Data on possible effects of the treatment on
      blood pressure, renal function as assessed by blood urea and creatinine, and
      kidney shrinkage as seen by serial computed tomography scanning were collected on
      all patients. RESULTS: Three patients had persistent, mild elevations of urea and
      creatinine levels, which did not require special treatment. All three also
      received cis-platinum. Ipsilateral kidney shrinkage was evident in most patients.
      In 19 patients the craniocaudal measurement of the kidney shrank by > or = 1.6
      cm. Shrinkage in other dimensions was also evident. The degree of atrophy was
      related to the volume of kidney irradiated. Only two patients developed
      hypertension, both at a low level of 150/90; one patient had had 40 Gy to the
      whole kidney, the other 40 Gy to half the kidney. Neither patient had elevated
      urea or creatinine. CONCLUSIONS: Notwithstanding the shrinkage to the irradiated
      part of the kidney, the treatment did not lead to clinically significant
      hypertension or renal dysfunction. The administration of cis-platinum to patients
      with gastric lymphoma that requires kidney irradiation should be further
      evaluated.

PMID- 9635716
TI  - Interstitial pneumonitis in acute leukemia patients submitted to T-depleted
      matched and mismatched bone marrow transplantation.
AB  - PURPOSE: To identify factors that could contribute to interstitial pneumonitis
      (IP), which remains one of the major causes of morbidity and mortality after both
      matched and mismatched bone marrow transplantation (BMT). METHODS AND PATIENTS:
      Ninety acute leukemia patients received an allogeneic T-depleted matched (n = 54)
      or mismatched (n = 36) BMT. They were preconditioned with total body irradiation
      (TBI), thiotepa, rabbit anti-thymocyte globulin, and cyclophosphamide. The TBI
      scheme was hyperfractionated in matched, and a single dose in mismatched
      patients. The dose to the lungs was reduced in both groups. RESULTS: Five of the
      54 matched patients developed IP. All cases were fatal. There were 16 cases of
      IP, 13 fatal, in the mismatched group. The probability of developing IP was 11.3
      +/- 4.9% and 48.6 +/- 9.0%, respectively. The between-group difference was
      statistically significant (p < 0.0001). The type of transplant and the TBI scheme
      were the most important parameters for IP development in univariate analysis,
      whereas acute graft-versus-host disease, disease stage and sex were
      nonsignificant. Median follow-up was 342 days (range 17-2900). CONCLUSIONS: The
      low incidence of IP in matched patients and the lack of idiopathic cases are
      evidence for the validity of the TBI schedule. In contrast, the incidence in
      mismatched patients remains too high; therefore, new strategies should be studied
      in an attempt to lower it.

PMID- 9635717
TI  - Cataracts after total body irradiation and bone marrow transplantation in
      patients with acute leukemia in complete remission: a study of the European Group
      for Blood and Marrow Transplantation.
AB  - PURPOSE: Advances in bone marrow transplantation (BMT) have consistently improved
      long-term survival. Therefore, evaluation of late complications such as cataracts
      is of paramount importance. METHODS AND MATERIALS: We analyzed data of 2149
      patients from the EBMT registry. A cohort of 1063 patients were evaluable for
      survival and ophthalmologic status after transplant for acute leukemia (AL) in
      first or second complete remission. Conditioning therapy included either single
      dose total body irradiation (STBI) or fractionated TBI (FTBI) grouped in
      different dose rates (low: LDR < or = 0.04 Gy/min; high: HDR > 0.04 Gy/min).
      RESULTS: The overall 10-year estimated cataract incidence (ECI) was 50%. It was
      60% in the STBI group, 43% in the FTBI group < or = 6 fractions, and 7% in the
      FTBI group > 6 fractions (p < 10(-4)). It was significantly lower (30%) in the
      LDR than in the HDR groups (59%;p < 10(-4)). Patients receiving heparin for veno
      occlusive disease prophylaxis had fewer cataracts than those who did not (10-year
      ECI: 33% vs. 53%, respectively;p = 0.04). The 10-year ECI was 65% in the
      allogeneic vs. 46% in the autologous BMT patients (p = 0.0018). Factors
      independently associated with an increased risk of cataract were an older age (>
      23 years), higher dose rate (> 0.04 Gy/min), allogeneic BMT, and steroid
      administration (> 100 days). The use of FTBI was associated with a decreased risk
      of cataract. Heparin administration was a protective factor in patients receiving
      STBI. In terms of cataract surgery, the unfavorable factors for requiring surgery
      were: age > 23 yr, STBI, dose rate > 0.04 Gy/min, chronic graft-vs.-host disease
      (cGvHD), and absence of heparin administration. Among the patients who required
      cataract surgery (111 out of 257), secondary posterior capsular opacification was
      observed in 15.7%. CONCLUSION: High dose rate and STBI are the main risk factors
      for cataract development and the need for surgery, and the administration of
      heparin has a protective role in cataractogenesis.

PMID- 9635718
TI  - Change in E-cadherin expression after X-ray irradiation of a human cancer cell
      line in vitro and in vivo.
AB  - PURPOSE: To investigate changes in E-cadherin expression after X-ray irradiation
      of a human cancer cell line in vitro and in vivo. METHODS AND MATERIALS: E
      cadherin expression on a human squamous cell carcinoma of the thyroid gland (T
      SCC cell), which was established in our laboratory, at 24 h after graded single
      doses of irradiation and at 7 successive times after 10-Gy irradiation were
      investigated in vitro by immunoblot analysis with the monoclonal antibody to
      human E-cadherin. The changes in E-cadherin expression caused by irradiation of T
      SCC tumors that were transplanted into athymic nude mice were also determined in
      vivo by immunohistochemical staining and immunoblot analysis in a similar fashion
      to that in vitro. RESULTS: In vitro studies revealed that E-cadherin expression
      had increased significantly on T-SCC cells at 24 h after irradiation with doses
      of 2 to 10 Gy and that, in a time-course analysis, the expression had increased
      significantly at 3 to 72 h after irradiation compared with an unirradiated
      control cell, although it was not observed at 1 h after irradiation. In in vivo
      studies, a significant increase in E-cadherin expression was observed at 24 h
      after irradiation with 5 and 10 Gy by immunohistochemical staining and time
      course studies demonstrated that E-cadherin increased temporarily at 12 to 24 h
      after 10-Gy irradiation; however, immunoblot analysis did not show alteration of
      E-cadherin expression by irradiation. CONCLUSION: X-ray irradiation upregulated E
      cadherin expression on T-SCC cells in vitro and in vivo.

PMID- 9635719
TI  - The effect of activation of wild-type p53 function on fluoropyrimidine-mediated
      radiosensitization.
AB  - PURPOSE: We have hypothesized that fluoropyrimidine-mediated (FdUrd)
      radiosensitization occurs in cells that inappropriately enter S phase in the
      presence of drug, resulting in defective repair of radiation-induced DNA damage
      (14). This model would predict that prevention of entry into S phase would
      abrogate sensitization produced by FdUrd. We wished to test this prediction by
      blocking S phase entry of HT29 human colon cancer cells. METHODS: We used HT29
      cells that had been transduced with a murine temperature-sensitive p53 (ts29G)
      and, as a control, HT29 cells transduced with a neomycin plasmid (HT29neo). The
      murine temperature-sensitive p53 demonstrates wild-type p53 function when cells
      are incubated at the permissive temperature (32 degrees C) and mutant p53
      function at the nonpermissive temperature (38 degrees C). We determined the
      effect of wt p53 function on FdUrd-mediated radiosensitization and cell cycle
      progression. RESULTS: Incubation of ts29G cells at the permissive temperature (32
      degrees C) activated p21 and blocked entry of cells into S phase. Whereas FdUrd
      greatly increased the radiosensitivity of HT29neo cells and ts29G cells incubated
      at 38 degrees C, FdUrd had no effect on the radiation sensitivity of ts29G cells
      incubated at the permissive temperature (32 degrees C). CONCLUSIONS: These
      findings are consistent with our hypothesis that FdUrd-mediated
      radiosensitization requires progression into S phase. It is possible that the
      heterogeneity of clinical responses seen after combined therapy with
      fluoropyrimidines and radiation is explained, in part, by differences among tumor
      cells in the control of S phase progression.

PMID- 9635720
TI  - Multivariate logistic analysis of dose-effect relationship and latency of
      radiomyelopathy after hyperfractionated and conventionally fractionated
      radiotherapy in animal experiments.
AB  - PURPOSE: We examined in rats whether the radiation tolerance of spinal cord is
      enhanced by using hyperfractionated radiotherapy compared to a conventional
      schedule. Higher tolerable doses to the spinal cord would allow dose escalation
      to the tumor and thus possibly lead to higher cure rates, especially in tumors
      with high cell proliferation. METHODS AND MATERIALS: Cervical spinal cord of 276
      healthy rats was irradiated over 6 weeks hyperfractionally with single doses
      ranging from 0.75-2.5 Gy up to total doses ranging from 45-150 Gy (60 fractions)
      and conventionally with single doses of 1.5-4.0 Gy up to total doses of 45-120 Gy
      (30 fractions). The rats were examined neurologically and sacrificed when
      paralysis of the hind legs occurred. After fixation, spinal cord was removed and
      examined histologically. Dose-effect relationship and latency from the beginning
      of radiotherapy to the onset of paralysis were computed and analyzed using a
      multivariate logistic regression model. RESULTS: The model fitted the observed
      data excellently. There were highly significant effects both for the dose level
      and for the treatment regimen. Latency analysis showed earlier and more intense
      acute side effects after hyperfractionation but radiomyelopathy occurred markedly
      later. CONCLUSIONS: The sparing effect of hyperfractionation on spinal cord as
      predicted by radiobiologists could be confirmed in our experiments. Thus, it
      seems possible to escalate tumor doses using hyperfractionation without enhanced
      risk to spinal cord but with higher probability of tumor cure.

PMID- 9635721
TI  - A realistic closed-form radiobiological model of clinical tumor-control data
      incorporating intertumor heterogeneity.
AB  - PURPOSE: To investigate the role of intertumor heterogeneity in clinical tumor
      control datasets and the relationship to in vitro measurements of tumor biopsy
      samples. Specifically, to develop a modified linear-quadratic (LQ) model
      incorporating such heterogeneity that it is practical to fit to clinical tumor
      control datasets. METHODS AND MATERIALS: We developed a modified version of the
      linear-quadratic (LQ) model for tumor control, incorporating a (lagged) time
      factor to allow for tumor cell repopulation. We explicitly took into account the
      interpatient heterogeneity in clonogen number, radiosensitivity, and repopulation
      rate. Using this model, we could generate realistic TCP curves using parameter
      estimates consistent with those reported from in vitro studies, subject to the
      inclusion of a radiosensitivity (or dose)-modifying factor. We then demonstrated
      that the model was dominated by the heterogeneity in alpha (tumor
      radiosensitivity) and derived an approximate simplified model incorporating this
      heterogeneity. This simplified model is expressible in a compact closed form,
      which it is practical to fit to clinical datasets. Using two previously analysed
      datasets, we fit the model using direct maximum-likelihood techniques and
      obtained parameter estimates that were, again, consistent with the experimental
      data on the radiosensitivity of primary human tumor cells. This heterogeneity
      model includes the same number of adjustable parameters as the standard LQ model.
      RESULTS: The modified model provides parameter estimates that can easily be
      reconciled with the in vitro measurements. The simplified (approximate) form of
      the heterogeneity model is a compact, closed-form probit function that can
      readily be fitted to clinical series by conventional maximum-likelihood
      methodology. This heterogeneity model provides a slightly better fit to the
      datasets than the conventional LQ model, with the same numbers of fitted
      parameters. The parameter estimates of the clinically important time factors and
      lag periods are very similar to those obtained from the conventional LQ model,
      but with slightly narrower confidence intervals, reflecting the better fit to the
      clinical data. DISCUSSION: We have demonstrated, as have others, the importance
      of intertumor heterogeneity in the response of patient populations to
      radiotherapy. With the possible inclusion of a radiosensitivity-modifying factor
      (in vitro/in vivo) of around 1.7, the in vivo data can be made consistent with
      the in vitro SF2 and Tpot data. Fitting two previously analyzed multicenter
      datasets indicated that previous analyses based on conventional LQ models gave
      results for clinically important time factors and lags periods that were not
      significantly biased by the failure to include intertumor heterogeneity, with
      slightly narrower confidence intervals, reflecting the better fit to the clinical
      data. The simple closed-form model we have developed allows direct estimation of
      the heterogeneity in radiosensitivity within clinical series, and should prove
      useful in the analysis of other clinical series.

PMID- 9635722
TI  - Review of eye plaque dosimetry based on AAPM Task Group 43 recommendations.
      American Association of Physicists in Medicine.
AB  - PURPOSE: AAPM Task Group 43 recently revised the dosimetry recommendations for
      125I seeds. We reviewed these guidelines and studied the effects of the
      recommendations on the prescription absorbed dose for patients who have undergone
      eye plaque therapy in our clinic. METHODS AND MATERIALS: 95 consecutive patients
      were chosen for this study. Absorbed doses at various points of clinical interest
      were computed based on conventional dose calculation algorithm (3, 4, 7) and TG
      43 recommendations. For three representative plaques chosen, the seeds are
      approximated by isotropic point and line sources, respectively, and absorbed
      doses were calculated at all points on the central axis of the plaque. RESULTS:
      For apical heights shorter than 5 mm, treatment plans using model 6711 seeds
      delivered 10-13% lower absorbed doses than that calculated previously. For
      lesions with apical heights 5 mm or larger, the absorbed dose was 6-12% lower
      than prescribed. Calculations for model 6702 seeds indicated that TG-43
      recommendations would produce 0-6% lower absorbed doses. Point doses calculated
      along the central axis of the plaque and isodose distributions at various levels
      showed that point source approximation of the seeds was clinically acceptable.
      CONCLUSIONS: TG-43 recommendations, if implemented, would result in lower
      absorbed doses unless the dose prescription is modified. The clinicians need to
      be aware of the dosimetric implications of these recommendations. The seeds may
      be approximated by isotropic point sources.

PMID- 9635723
TI  - Impact of beam energy and field margin on penumbra at lung tumor-lung parenchyma
      interfaces.
AB  - PURPOSE: To determine the characteristics of the penumbra in the region of the
      lung tumor-lung parenchyma interfaces for various radiation beam energies and
      various field margins. METHODS AND MATERIALS: A phantom simulating the thoracic
      cavity with a tumor arising within the lung parenchyma was irradiated with
      opposed 6-, 10-, and 18-MV photon beams. Beam profiles were obtained at the
      tumor's surface and midplane using radiographic film. The field edge varied from
      0.0 to 3.5 cm from the gross tumor volume. The effective penumbra (distance from
      80 to 20% dose) and beam fringe (distance from 90 to 50% dose) were measured.
      Clinically acceptable beam profiles were defined as those in which no point of
      the planning target volume (gross tumor volume plus a 1-cm margin) received less
      than 95% of the central tumor dose. RESULTS: Mean effective penumbra and beam
      fringe were found to differ in a statistically significant manner with respect to
      energy, but not with distance from field edge to gross tumor volume. With the
      field edge < or = 1.5 cm from the gross tumor volume, no energy provided an
      acceptable dose distribution, as defined above. With the field edge 2 cm from the
      gross tumor volume, 6 and 10 MV provided acceptable dose distributions, but 18 MV
      did not. With the field edge > or = 2.5 cm from the gross tumor volume, all
      energies provided acceptable dose distributions. CONCLUSION: For irradiation of
      lung carcinomas in which the planning target volume includes a margin of normal
      lung tissue, 6- and 10-MV opposed beams yield a superior dose distribution with
      respect to penumbra at the tumor's surface and midplane, with the field edge
      placed 2 cm from the gross tumor volume. To achieve an equivalent distribution
      with 18-MV photons, a distance of 2.5 cm from field edge to the gross tumor
      volume is necessary, leading to an increase in normal lung tissue irradiated.

PMID- 9635724
TI  - The use of adaptive radiation therapy to reduce setup error: a prospective
      clinical study.
AB  - PURPOSE: Adaptive Radiation Therapy (ART) is a feedback treatment process that
      optimizes a patient's treatment according to the patient specific information
      measured during the course of treatment. Utilizing an electronic portal imaging
      device (EPID) and a computer-controlled multileaf collimator (MLC), the ART
      process is currently being implemented in our clinic to improve the treatment
      accuracy by compensating for the treatment setup error. A prospective study was
      conducted to evaluate the feasibility and efficacy of the ART process for
      clinical use. METHODS AND MATERIALS: The prospective study included 20 patients
      who underwent conventional radiotherapy on a linear accelerator equipped with an
      EPID and a MLC. No specific changes were made in the routine clinical procedures
      except daily portal images were obtained for each treatment field. Two
      dimensional setup error for each treatment field was then measured offline using
      a software tool. The measured setup errors from initial treatment days were used
      to predict the systematic and random setup errors for each treatment field. An
      adjustment decision was made if the predicted systematic error was larger than or
      equal to 2 mm. Furthermore, the treatment field was extended if the predicted
      random setup error could not be effectively compensated by the predefined
      treatment setup margin. Instead of the conventional approach of patient
      repositioning, setup adjustment was implemented by reshaping the MLC field. The
      entire process from measuring setup error to reshaping the MLC field was
      performed offline through a computer network. After completion of a patient's
      treatment, the systematic and random setup errors after adjustment were compared
      with those predicted prior to the adjustment. The accuracy of the adjustment, and
      the reliability and stability of the process were analyzed. RESULTS: Treatment
      fields of 13 patients were modified to correct for systematic errors. The mean
      systematic error was 4 mm with a range of 2 to 7 mm before adjustment. It was
      reduced to 0.5 mm with a range of 0.2 to 1.4 mm after adjustment. There was no
      significant difference in random setup errors before and after adjustment. The
      ART process was found to be stable, as more than 95% of patient specific setup
      margins were predictable within 1 mm using the first four to nine fractions of
      treatment, confirming the feasibility of treatment plan reoptimization with the
      ART process. CONCLUSIONS: The prospective study demonstrates that the ART process
      can be effectively implemented in routine clinical practice to improve treatment
      accuracy. This process is also ready to be further extended to reoptimize the
      treatment plan by incorporating the predicted patient specific setup variation.

PMID- 9635725
TI  - Use of a simulator with CT option in radiotherapy of macular degeneration.
AB  - PURPOSE: To assess the accuracy of a conventional simulation procedure in
      radiotherapy of age-related macular degeneration. METHODS AND MATERIALS: A
      computed tomographic (CT) extension attached to the treatment simulator was used
      to acquire CT images immediately after conventional simulation in 18 patients
      referred for treatment of age-related macular degeneration. Analysis was
      performed on 16 one-sided treatment cases for whom images were obtained. Error
      was estimated by the displacement between the observed treatment isocenter and
      the intended isocenter based on reconstructed eye geometry. RESULTS: Based on
      single slice measurements, the mean error amplitude was 2.3 mm (range 0.2-5.6).
      Based on three-dimensional eye globe reconstruction, the mean error amplitude was
      2.8 mm (range 0.8-5.3). An incidental finding previously unreported was the lower
      image quality at the center of the simulator-CT image acquisition field.
      CONCLUSIONS: Small but significant errors from conventional simulation were
      noted. The integrated simulation-CT procedure may help correct the errors to
      improve the accuracy of simulation setup. The lower image quality at the center
      of image acquisition field requires adaptation of the simulation-CT procedure.

PMID- 9635726
TI  - Regarding dose prescription for radiotherapy in the lung: Klein et al. IJROBP
      37:1163-1170; 1997.

PMID- 9635727
TI  - Making movies of molecular motions.

PMID- 9635728
TI  - Molecular dynamics simulations of ion channels: how far have we gone and where
      are we heading?

PMID- 9635729
TI  - Cells use the singular properties of different channels to produce unique
      electrical songs.

PMID- 9635730
TI  - The pH-induced release of iron from transferrin investigated with a continuum
      electrostatic model.
AB  - A reduction in pH induces the release of iron from transferrin in a process that
      involves a conformational change in the protein from a closed to an open form.
      Experimental evidence suggests that there must be changes in the protonation
      states of certain, as yet not clearly identified, residues in the protein
      accompanying this conformational change. Such changes in protonation states of
      residues and the consequent changes in electrostatic interactions are assumed to
      play a large part in the mechanism of release of iron from transferrin. Using the
      x-ray crystal structures of human ferri- and apo-lactoferrin, we calculated the
      pKa values of the titratable residues in both the closed (iron-loaded) and open
      (iron-free) conformations with a continuum electrostatic model. With the
      knowledge of a residue's pKa value, its most probable protonation state at any
      specified pH may be determined. The preliminary results presented here are in
      good agreement with the experimental observation that the binding of ferric iron
      and the synergistic anion bicarbonate/carbonate results in the release of
      approximately three H+ ions. It is suggested that the release of these three H+
      ions may be accounted for, in most part, by the deprotonation of the bicarbonate
      and residues Tyr-92, Lys-243, Lys-282, and Lys-285 together with the protonation
      of residues Asp-217 and Lys-277.

PMID- 9635731
TI  - Low-resolution structures of proteins in solution retrieved from X-ray scattering
      with a genetic algorithm.
AB  - Small-angle x-ray solution scattering (SAXS) is analyzed with a new method to
      retrieve convergent model structures that fit the scattering profiles. An
      arbitrary hexagonal packing of several hundred beads containing the problem
      object is defined. Instead of attempting to compute the Debye formula for all of
      the possible mass distributions, a genetic algorithm is employed that efficiently
      searches the configurational space and evolves best-fit bead models. Models from
      different runs of the algorithm have similar or identical structures. The
      modeling resolution is increased by reducing the bead radius together with the
      search space in successive cycles of refinement. The method has been tested with
      protein SAXS (0.001 < S < 0.06 A(-1)) calculated from x-ray crystal structures,
      adding noise to the profiles. The models obtained closely approach the volumes
      and radii of gyration of the known structures, and faithfully reproduce the
      dimensions and shape of each of them. This includes finding the active site
      cavity of lysozyme, the bilobed structure of gamma-crystallin, two domains
      connected by a stalk in betab2-crystallin, and the horseshoe shape of pancreatic
      ribonuclease inhibitor. The low-resolution solution structure of lysozyme has
      been directly modeled from its experimental SAXS profile (0.003 < S < 0.03 A(
      1)). The model describes lysozyme size and shape to the resolution of the
      measurement. The method may be applied to other proteins, to the analysis of
      domain movements, to the comparison of solution and crystal structures, as well
      as to large macromolecular assemblies.

PMID- 9635732
TI  - Periodic orbits: a new language for neuronal dynamics.
AB  - A new nonlinear dynamical analysis is applied to complex behavior from neuronal
      systems. The conceptual foundation of this analysis is the abstraction of
      observed neuronal activities into a dynamical landscape characterized by a
      hierarchy of "unstable periodic orbits" (UPOs). UPOs are rigorously identified in
      data sets representative of three different levels of organization in mammalian
      brain. An analysis based on UPOs affords a novel alternative method of decoding,
      predicting, and controlling these neuronal systems.

PMID- 9635733
TI  - A molecular dynamics study of the pores formed by Escherichia coli OmpF porin in
      a fully hydrated palmitoyloleoylphosphatidylcholine bilayer.
AB  - In this paper we study the properties of pores formed by OmpF porin from
      Escherichia coli, based on a molecular dynamics simulation of the OmpF trimer,
      318 palmitoyl-oleoyl-phosphatidylethanolamine lipids, 27 Na+ ions, and 12,992
      water molecules. After equilibration and a nanosecond production run, the OmpF
      trimer exhibits a C-alpha root mean square deviation from the crystal structure
      of 0.23 nm and a stable secondary structure. No evidence is found for large-scale
      motions of the L3 loop. We investigate the pore dimensions, conductance, and the
      properties of water inside the pore. This water forms a complicated pattern, even
      when averaged over 1 ns of simulation time. Around the pore constriction zone the
      water dipoles are highly structured in the plane of the membrane, oriented by the
      strong transversal electric field. In addition, there is a net orientation along
      the pore axis pointing from the extracellular to the intracellular side of the
      bilayer. The diffusion coefficients of water inside the pore are greatly reduced
      compared to bulk. We compare our results to results from model pores (Breed et
      al., 1996. Biophys. J. 70:1 643-1 661; Sansom et al. 1997. Biophys. J. 73:2404
      241 5) and discuss implications for further theoretical work.

PMID- 9635734
TI  - A physicochemical approach for predicting the effectiveness of peptide-based gene
      delivery systems for use in plasmid-based gene therapy.
AB  - Novel synthetic peptides, based on carrier peptide analogs (YKAKnWK) and an
      amphipathic peptide (GLFEALLELLESLWELLLEA), have been formulated with DNA
      plasmids to create peptide-based gene delivery systems. The carrier peptides are
      used to condense plasmids into nanoparticles with a hydrodynamic diameter (DH)
      ranging from 40 to 200 nm, which are sterically stable for over 100 h. Size and
      morphology of the carrier peptide/plasmid complex have been determined by photon
      correlation spectroscopy (PCS) and transmission electron microscopy (TEM),
      respectively. The amphipathic peptide is used as a pH-sensitive lytic agent to
      facilitate release of the plasmid from endosomes after endocytosis of the
      peptide/plasmid complex. Hemolysis assays have shown that the amphipathic peptide
      destabilizes lipid bilayers at low pH, mimicking the properties of viral
      fusogenic peptides. However, circular dichroism studies show that unlike the
      viral fusion peptides, this amphipathic peptide loses some of its alpha-helical
      structure at low pH in the presence of liposomes. The peptide-based gene delivery
      systems were tested for transfection efficiency in a variety of cell lines,
      including 14-day C2C12 mouse myotubes, using gene expression systems containing
      the beta-galactosidase reporter gene. Transfection data demonstrate a correlation
      between in vitro transfection efficiency and the combination of several physical
      properties of the peptide/plasmid complexes, including 1) DNA dose, 2) the zeta
      potential of the particle, 3) the requirement of both lytic and carrier peptides,
      and 4) the number of lysine residues associated with the carrier peptide.
      Transfection data on 14-day C2C12 myotubes utilizing the therapeutic human growth
      hormone gene formulated in an optimal peptide gene delivery system show an
      increase in gene expression over time, with a maximum in protein levels at 96 h
      (approximately 18 ng/ml).

PMID- 9635735
TI  - Geometry and physics of catenanes applied to the study of DNA replication.
AB  - The concept of ideal geometric configurations was recently applied to the
      classification and characterization of various knots. Different knots in their
      ideal form (i.e., the one requiring the shortest length of a constant-diameter
      tube to form a given knot) were shown to have an overall compactness proportional
      to the time-averaged compactness of thermally agitated knotted polymers forming
      corresponding knots. This was useful for predicting the relative speed of
      electrophoretic migration of different DNA knots. Here we characterize the ideal
      geometric configurations of catenanes (called links by mathematicians), i.e.,
      closed curves in space that are topologically linked to each other. We
      demonstrate that the ideal configurations of different catenanes show
      interrelations very similar to those observed in the ideal configurations of
      knots. By analyzing literature data on electrophoretic separations of the torus
      type of DNA catenanes with increasing complexity, we observed that their
      electrophoretic migration is roughly proportional to the overall compactness of
      ideal representations of the corresponding catenanes. This correlation does not
      apply, however, to electrophoretic migration of certain replication
      intermediates, believed up to now to represent the simplest torus-type catenanes.
      We propose, therefore, that freshly replicated circular DNA molecules, in
      addition to forming regular catenanes, may also form hemicatenanes.

PMID- 9635736
TI  - Contributions of linker histones and histone H3 to chromatin structure: scanning
      force microscopy studies on trypsinized fibers.
AB  - Little is known about the mechanisms that organize linear arrays of nucleosomes
      into the three-dimensional structures of extended and condensed chromatin fibers.
      We have earlier defined, from scanning force microscopy (SFM) and mathematical
      modeling, a set of simple structural determinants of extended fiber morphology,
      the critical parameters being the entry-exit angle between consecutive linkers
      and linker length. Here we study the contributions of the structural domains of
      the linker histones (LHs) and of the N-terminus of histone H3 to extended fiber
      morphology by SFM imaging of progressively trypsinized chromatin fibers. We find
      that cleavage of LH tails is associated with a lengthening of the
      internucleosomal center-to-center distance, and that the somewhat later cleavage
      of the N-terminus of histone H3 is associated with a flattening of the fiber. The
      persistence of the "zigzag" fiber morphology, even at the latest stages of
      trypsin digestion, can be attributed to the retention of the globular domain of
      LH in the fiber.

PMID- 9635737
TI  - Linker histone tails and N-tails of histone H3 are redundant: scanning force
      microscopy studies of reconstituted fibers.
AB  - The mechanisms responsible for organizing linear arrays of nucleosomes into the
      three-dimensional structure of chromatin are still largely unknown. In a
      companion paper (Leuba, S. H., et al. 1998. Biophys. J. 74:2823-2829), we study
      the contributions of linker histone domains and the N-terminal tail of core
      histone H3 to extended chromatin fiber structure by scanning force microscopy
      imaging of mildly trypsinized fibers. Here we complement and extend these studies
      by scanning force microscopy imaging of selectively reconstituted chromatin
      fibers, which differ in subtle but distinctive ways in their histone composition.
      We demonstrate an absolute requirement for the globular domain of the linker
      histones and a structural redundancy of the tails of linker histones and of
      histone H3 in determining conformational stability.

PMID- 9635738
TI  - Direct visualization of dynamic protein-DNA interactions with a dedicated atomic
      force microscope.
AB  - Photolyase DNA interactions and the annealing of restriction fragment ends are
      directly visualized with the atomic force microscope (AFM). To be able to
      interact with proteins, DNA must be loosely bound to the surface. When MgCl2 is
      used to immobilize DNA to mica, DNA is attached to the surface at distinct sites.
      The pieces of DNA in between are free to move over the surface and are available
      for protein interaction. After implementation of a number of instrumental
      improvements, the molecules can be visualized routinely, under physiological
      conditions and with molecular resolution. Images are acquired reproducibly
      without visible damage for at least 30 min, at a scan rate of 2 x 2 microm2/min
      and a root mean square noise of less than 0.2 nm. Nonspecific photolyase DNA
      complexes were visualized, showing association, dissociation, and movement of
      photolyase over the DNA. The latter result suggests a sliding mechanism by which
      photolyase can scan DNA for damaged sites. The experiments illustrate the
      potential that AFM presents for modern molecular biology.

PMID- 9635739
TI  - Deexcitation of cardiac cells.
AB  - Excitation and deexcitation are fundamental phenomena in the electrophysiology of
      excitable cells. Both of them can be induced by stimulating a cell with
      intracellularly injected currents. With extracellular stimulation, deexcitation
      was never observed; only cell excitation was found. Why? A generic model with two
      variables (FitzHugh) predicts that an extracellular stimulus can both excite the
      cell and terminate the action potential (AP). Our experiments with single mouse
      myocytes have shown that short (2-5 ms) extracellular pulses never terminated the
      AP. This result agrees with our numerical experiments with the Beeler-Reuter
      model. To analyze the problem, we exploit the separation of time scales to derive
      simplified models with fewer equations. Our analysis has shown that the very
      specific form of the current-voltage (I-V) characteristics of the time
      independent potassium current (almost no dependence on voltage for positive
      membrane potentials) is responsible here. When the shape of the I-V
      characteristics of potassium currents was modified to resemble that in ischemic
      tissues, or when the external potassium concentration (K0) is increased, the AP
      was terminated by extracellular pulses. These results may be important for
      understanding the mechanisms of defibrillation.

PMID- 9635741
TI  - Multivariate curve resolution: a possible tool in the detection of intermediate
      structures in protein folding.
AB  - Different multivariate data analysis techniques based on factor analysis and
      multivariate curve resolution are shown for the study of biochemical evolutionary
      processes like conformational changes and protein folding. Several simulated CD
      spectral data sets describing different hypothetical protein folding pathways are
      analyzed and discussed in relation to the feasibility of factor analysis
      techniques to detect and resolve the number of components needed to explain the
      evolution of the CD spectra corresponding to the process (i.e., to detect the
      presence of intermediate forms). When more than two components (the native and
      unordered forms) are needed to explain the evolution of the spectra, an iterative
      multivariate curve resolution procedure based on an alternating least squares
      algorithm is proposed to estimate the CD spectrum corresponding to the
      intermediate form.

PMID- 9635740
TI  - Spontaneous-curvature theory of clathrin-coated membranes.
AB  - Clathrin-coated membranes are precursors to coated vesicles in the receptor
      mediated endocytic pathway. In this paper we present a physical model for the
      first steps of the transformation of a clathrin-coated membrane into a coated
      vesicle. The theory is based on in vitro cytoplasmic acidification experiments of
      Heuser (J. Cell Biol. 108:401-411) that suggest the transformation proceeds by
      changes in the chemical environment of the clathrin lattice, wherein the chemical
      environment determines the amount of intrinsic, or spontaneous, curvature of the
      network. We show that a necessary step of the transformation, formation of free
      pentagons in the clathrin network, can proceed via dislocation unbinding, driven
      by changes in the spontaneous curvature. Dislocation unbinding is shown to favor
      formation of coated vesicles that are quite small compared to those predicted by
      the current continuum theories, which do not include the topology of the clathrin
      lattice.

PMID- 9635743
TI  - Derivation of unstirred-layer transport number equations from the Nernst-Planck
      flux equations.
AB  - Since the late 1960s it has been known that the passage of current across a
      membrane can give rise to local changes in salt concentration in unstirred layers
      or regions adjacent to that membrane, which in turn give rise to the development
      of slow transient diffusion potentials and osmotic flows across those membranes.
      These effects have been successfully explained in terms of transport number
      discontinuities at the membrane-solution interface, the transport number of an
      ion reflecting the proportion of current carried by that ion. Using the standard
      definitions for transport numbers and the regular diffusion equations, these
      polarization or transport number effects have been analyzed and modeled in a
      number of papers. Recently, the validity of these equations has been questioned.
      This paper has demonstrated that, by going back to the Nernst-Planck flux
      equations, exactly the same resultant equations can be derived and therefore that
      the equations derived directly from the transport number definitions and standard
      diffusion equations are indeed valid.

PMID- 9635742
TI  - Electromechanical coupling model of gating the large mechanosensitive ion channel
      (MscL) of Escherichia coli by mechanical force.
AB  - We have developed a theoretical electromechanical coupling (EMC) model of gating
      of the large-conductance mechanosensitive ion channel (MscL). The model presents
      the first attempt to explain the pressure-dependent transitions between the
      closed and open channel conformations on a molecular level by assuming 1) a
      homohexameric structural model of the channel, 2) electrostatic interactions
      between various domains of the homohexamer, 3) structural flexibility of the N
      terminal portion of the monomer, and 4) mechanically and electrostatically
      induced displacement of the N-terminal domain relative to other structural
      domains of the protein. In the EMC model, 12 membrane-spanning alpha-helices (six
      each of the M1 and M2 transmembrane domains of the MscL monomer), are envisaged
      to line the channel pore with a diameter of 40 A, whereas the N- and C-termini
      are oriented toward each other inside the pore when the channel is closed. The
      model proposes that stretching the membrane bilayer by mechanical force causes
      the monomers to be pulled away from and slightly tilted toward each other. This
      relative movement of alpha-helices could serve as a trigger to initiate a "swing
      like" motion of the N-terminus around the glycine residue G14 that may act as a
      pivot. The analysis of the attractive and repulsive coulomb forces between all
      domains of the channel homohexamer suggested that an inclination angle of
      approximately 3.0 degrees - 4.1 degrees between the oppositely oriented channel
      monomers should suffice for the N-terminus to turn away from other domains
      causing the channel to open. According to the EMC model the minimal free energy
      change, deltaG, that could initiate the opening of the channel was 2 kT. Also,
      the model predicted that the negative pressure required for channel open
      probability, Po = 0.5, should be between 50 and 80 mmHg. These values were in a
      good agreement with the experimentally estimated pressures of 60-70 mmHg obtained
      with the MscL reconstituted in liposomes. Furthermore, consistent with a notion
      that the N-terminus may present a mechanosensitive structural element providing a
      mechanism to open the MscL by mechanical force, the model provides a simple
      explanation for the variations in pressure sensitivity observed with several MscL
      mutants having either deletions or substitutions in N- or C-terminus, or site
      directed mutations in the S2-S3 loop.

PMID- 9635744
TI  - Importance of explicit salt ions for protein stability in molecular dynamics
      simulation.
AB  - The accurate and efficient treatment of electrostatic interactions is one of the
      challenging problems of molecular dynamics simulation. Truncation procedures such
      as switching or shifting energies or forces lead to artifacts and significantly
      reduced accuracy. The particle mesh Ewald (PME) method is one approach to
      overcome these problems by providing a computationally efficient means of
      calculating all long-range electrostatic interactions in a periodic simulation
      box by use of fast Fourier transformation techniques. For the application of the
      PME method to the simulation of a protein with a net charge in aqueous solution,
      counterions are added to neutralize the system. The usual procedure is to add
      charge-balancing counterions close to charged residues to neutralize the protein
      surface. In the present article, we show that for MD simulation of a small
      protein of marginal stability, the YAP-WW domain, explicit modeling of 0.2 M
      ionic strength (in addition to the charge-balancing counterions) is necessary to
      maintain a stable protein structure. Without explicit ions throughout the
      periodic simulation box, the charge-balancing counterions on the protein surface
      diffuse away from the protein, resulting in destruction of the beta-sheet
      secondary structure of the WW domain.

PMID- 9635745
TI  - Streaming potentials in gramicidin channels measured with ion-selective
      microelectrodes.
AB  - Streaming potentials have been measured for gramicidin channels with a new method
      employing ion-selective microelectrodes. It is shown that ideally ion-selective
      electrodes placed at the membrane surface record the true streaming potential.
      Using this method for ion concentrations below 100 mM, approximately seven water
      molecules are transported whenever a sodium, potassium, or cesium ion, passes
      through the channel. This new method confirms earlier measurements (Rosenberg,
      P.A., and A. Finkelstein. 1978. Interaction of ions and water in gramicidin A
      channels. J. Gen. Physiol. 72:327-340) in which the streaming potentials were
      calculated as the difference between electrical potentials measured in the
      presence of gramicidin and in the presence of the ion carriers valinomycin and
      nonactin.

PMID- 9635746
TI  - Cluster organization of ion channels formed by the antibiotic syringomycin E in
      bilayer lipid membranes.
AB  - The cyclic lipodepsipeptide, syringomycin E, when incorporated into planar lipid
      bilayer membranes, forms two types of channels (small and large) that are
      different in conductance by a factor of sixfold. To discriminate between a
      cluster organization-type channel structure and other possible different
      structures for the two channel types, their ionic selectivity and pore size were
      determined. Pore size was assessed using water-soluble polymers. Ion selectivity
      was found to be essentially the same for both the small and large channels. Their
      reversal (zero current) potentials with the sign corresponding to anionic
      selectivity did not differ by more than 3 mV at a twofold electrolyte gradient
      across the bilayer. Reduction in the single-channel conductance induced by
      poly(ethylene glycol)s of different molecular weights demonstrated that the
      aqueous pore sizes of the small and large channels did not differ by more than 2%
      and were close to 1 nm. Based on their virtually identical selectivity and size,
      we conclude that large syringomycin E channels are clusters of small ones
      exhibiting synchronous opening and closing.

PMID- 9635747
TI  - The sensor regions of VDAC are translocated from within the membrane to the
      surface during the gating processes.
AB  - The motion of the sensor regions in a mitochondrial voltage-gated channel called
      VDAC were probed by attaching biotin at specific locations and determining its
      ability to bind to added streptavidin. Site-directed mutagenesis was used to
      introduce single cysteine residues into Neurospora crassa VDAC (naturally lacks
      cysteine). These were chemically biotinylated and reconstituted into planar
      phospholipid membranes. In the 19 sites examined, only two types of results were
      observed upon streptavidin addition: in type 1, channel conductance was reduced,
      but voltage gating could proceed; in type 2, channels were locked in a closed
      state. The result at type 1 sites is interpreted as streptavidin binding to sites
      in static regions close to the channel opening. The binding sterically interferes
      with ion flow. The result at type 2 sites indicates that these are located on a
      mobile domain and coincide with the previously identified sensor regions. The
      findings are consistent with closure resulting from the movement of a domain from
      within the transmembrane regions to the membrane surface. No single site was
      accessible to streptavidin from both membrane surfaces, indicating that the
      motion is limited. From the streptavidin-induced reduction in conductance at type
      1 sites, structural information was obtained about the location of these sites.

PMID- 9635748
TI  - Slow inactivation in human cardiac sodium channels.
AB  - The available pool of sodium channels, and thus cell excitability, is regulated
      by both fast and slow inactivation. In cardiac tissue, the requirement for
      sustained firing of long-duration action potentials suggests that slow
      inactivation in cardiac sodium channels may differ from slow inactivation in
      skeletal muscle sodium channels. To test this hypothesis, we used the macropatch
      technique to characterize slow inactivation in human cardiac sodium channels
      heterologously expressed in Xenopus oocytes. Slow inactivation was isolated from
      fast inactivation kinetically (by selectively recovering channels from fast
      inactivation before measurement of slow inactivation) and structurally (by
      modification of fast inactivation by mutation of IFM1488QQQ). Time constants of
      slow inactivation in cardiac sodium channels were larger than previously reported
      for skeletal muscle sodium channels. In addition, steady-state slow inactivation
      was only 40% complete in cardiac sodium channels, compared to 80% in skeletal
      muscle channels. These results suggest that cardiac sodium channel slow
      inactivation is adapted for the sustained depolarizations found in normally
      functioning cardiac tissue. Complete slow inactivation in the fast inactivation
      modified IFM1488QQQ cardiac channel mutant suggests that this impairment of slow
      inactivation may result from an interaction between fast and slow inactivation.

PMID- 9635749
TI  - The N-terminus of the K channel KAT1 controls its voltage-dependent gating by
      altering the membrane electric field.
AB  - Functional roles of different domains (pore region, S4 segment, N-terminus) of
      the KAT1 potassium channel in its voltage-dependent gating were
      electrophysiologically studied in Xenopus oocytes. The KAT1 properties did not
      depend on the extracellular K+ concentration or on residue H267, equivalent to
      one of the residues known to be important in C-type inactivation in Shaker
      channels, indicating that the hyperpolarization-induced KAT1 inward currents are
      related to the channel activation rather than to recovery from inactivation.
      Neutralization of a positively charged amino acid in the S4 domain (R176S)
      reduced the gating charge movement, suggesting that it acts as a voltage-sensing
      residue in KAT1. N-terminal deletions alone (e.g., delta20-34) did not affect the
      gating charge movement. However, the deletions paradoxically increased the
      voltage sensitivity of the R176S mutant channel, but not that of the wild-type
      channel. We propose a simple model in which the N-terminus determines the KAT1
      voltage sensitivity by contributing to the electric field sensed by the voltage
      sensor.

PMID- 9635750
TI  - A novel voltage clamp technique for mapping ionic currents from cultured skeletal
      myotubes.
AB  - The biophysical properties and cellular distribution of ion channels largely
      determine the input/output relationships of electrically excitable cells. A
      variety of patch pipette voltage clamp techniques are available to characterize
      ionic currents. However, when used by themselves, such techniques are not well
      suited to the task of mapping low-density channel distributions. We describe here
      a new voltage clamp method (the whole cell loose patch (WCLP) method) that
      combines whole-cell recording through a tight-seal pipette with focal
      extracellular stimulation through a loose-seal pipette. By moving the stimulation
      pipette across the cell surface and using a stationary whole-cell pipette to
      record the evoked patch currents, this method should be suitable for mapping
      channel distributions, even on large cells possessing low channel densities. When
      we applied this method to the study of currents in cultured chick myotubes, we
      found that the cell cable properties and the series resistance of the recording
      pipette caused significant filtering of the membrane currents, and that the
      filter characteristics depended in part upon the distance between the stimulating
      and recording pipettes. We describe here how we determined the filter impulse
      response for each loose-seal pipette placement and subsequently recovered
      accurate estimates of patch membrane current through deconvolution.

PMID- 9635751
TI  - Formation of giant liposomes promoted by divalent cations: critical role of
      electrostatic repulsion.
AB  - Spontaneous formation of giant unilamellar liposomes in a gentle hydration
      process, as well as the adhesion energy between liposomal membranes, has been
      found to be dependent on the concentration of divalent alkali cations, Ca2+ or
      Mg2+, in the medium. With electrically neutral phosphatidylcholine (PC), Ca2+ or
      Mg2+ at 1-30 mM greatly promoted liposome formation compared to low yields in
      nonelectrolyte or potassium chloride solutions. When negatively charged
      phosphatidylglycerol (PG) was mixed at 10%, the yield was high in nonelectrolytes
      but liposomes did not form at 3-10 mM CaCl2. In the adhesion test with
      micropipette manipulation, liposomal membranes adhered to each other only in a
      certain range of CaCl2 concentrations, which agreed with the range where liposome
      did not form. The adhesion range shifted to higher Ca2+ concentrations as the
      amount of PG was increased. These results indicate that the divalent cations bind
      to and add positive charges to the lipids, and that membranes are separated and
      stabilized in the form of unilamellar liposomes when net charges on the membranes
      produce large enough electrostatic repulsion. Under the assumption that the
      maximum of adhesion energy within an adhesive range corresponds to exact charge
      neutralization by added Ca2+, association constants of PC and PG for Ca2+ were
      estimated at 7.3 M(-1) and 86 M(-1), respectively, in good agreement with
      literature values.

PMID- 9635753
TI  - Effect of extrusion pressure and lipid properties on the size and polydispersity
      of lipid vesicles.
AB  - The production of vesicles, spherical shells formed from lipid bilayers, is an
      important aspect of their recent application to drug delivery technologies. One
      popular production method involves pushing a lipid suspension through cylindrical
      pores in polycarbonate membranes. However, the actual mechanism by which the
      polydisperse, multilamellar lipid suspension breaks up into a relatively
      monodisperse population of vesicles is not well understood. To learn about
      factors influencing this process, we have characterized vesicles produced under
      different extrusion parameters and from different lipids. We find that extruded
      vesicles are only produced above a certain threshold extrusion pressure and have
      sizes that depend on the extrusion pressure. The minimum pressure appears to be
      associated with the lysis tension of the lipid bilayer rather than any bending
      modulus of the system. The flow rate of equal concentration lipid solutions
      through the pores, after being corrected for the viscosity of water, is
      independent of lipid properties.

PMID- 9635752
TI  - Phase transitions in films of lung surfactant at the air-water interface.
AB  - Pulmonary surfactant maintains a putative surface-active film at the air-alveolar
      fluid interface and prevents lung collapse at low volumes. Porcine lung
      surfactant extracts (LSE) were studied in spread and adsorbed films at 23 +/- 1
      degrees C using epifluorescence microscopy combined with surface balance
      techniques. By incorporating small amounts of fluorescent probe 1-palmitoyl-2
      nitrobenzoxadiazole dodecanoyl phosphatidylcholine (NBD-PC) in LSE films the
      expanded (fluid) to condensed (gel-like) phase transition was studied under
      different compression rates and ionic conditions. Films spread from solvent and
      adsorbed from vesicles both showed condensed (probe-excluding) domains dispersed
      in a background of expanded (probe-including) phase, and the appearance of the
      films was similar at similar surface pressure. In quasistatically compressed LSE
      films the appearance of condensed domains occurred at a surface pressure (pi) of
      13 mN/m. Such domains increased in size and amounts as pi was increased to 35
      mN/m, and their amounts appeared to decrease to 4% upon further compression to 45
      mN/m. Above pi of 45 mN/m the LSE films had the appearance of filamentous
      materials of finely divided dark and light regions, and such features persisted
      up to a pi near 68 mN/m. Some of the condensed domains had typical kidney bean
      shapes, and their distribution was similar to those seen previously in films of
      dipalmitoylphosphatidylcholine (DPPC), the major component of surfactant. Rapid
      cyclic compression and expansion of LSE films resulted in features that indicated
      a possible small (5%) loss of fluid components from such films or an increase in
      condensation efficiency over 10 cycles. Calcium (5 mM) in the subphase of LSE
      films altered the domain distribution, decreasing the size and increasing the
      number and total amount of condensed phase domains. Calcium also caused an
      increase in the value of pi at which the maximum amount of independent condensed
      phase domains were observed to 45 mN/m. It also induced formation of large
      amounts of novel, nearly circular domains containing probe above pi of 50 mN/m,
      these domains being different in appearance than any seen at lower pressures with
      calcium or higher pressures in the absence of calcium. Surfactant protein-A (SP
      A) adsorbed from the subphase onto solvent-spread LSE films, and aggregated
      condensed domains in presence of calcium. This study indicates that spread or
      adsorbed lung surfactant films can undergo expanded to condensed, and possibly
      other, phase transitions at the air-water interface as lateral packing density
      increases. These phase transitions are affected by divalent cations and SP-A in
      the subphase, and possibly by loss of material from the surface upon cyclic
      compression and expansion.

PMID- 9635754
TI  - Kinetics of synaptic depression and vesicle recycling after tetanic stimulation
      of frog motor nerve terminals.
AB  - We measured the time courses of two key components of the synaptic vesicle cycle
      during recovery from synaptic depression under different conditions, and used
      this and other information to create a kinetic model of the vesicle cycle. End
      plate potential (EPP) amplitudes were used to follow recovery from synaptic
      depression after different amounts of tetanic stimulation. This provided an
      estimate of the time course of vesicle mobilization from the reserve pool to the
      docked (readily releasable) pool. In addition, FM1-43 was used to measure the
      rate of membrane retrieval after tetanic stimulation, and the amount of membrane
      transferred to the surface membrane. This provided a measure of the rate of
      refilling of the reserve pool with recycled vesicles. The time courses of both
      synaptic depression and endocytosis were slowed by prolonged tetanic stimulation.
      This behavior could be fitted by a simple model, assuming a first-order kinetics
      for both vesicle endocytosis and mobilization. The results show that a nearly 20
      fold decrease in the rate constant of endocytosis greatly delays refilling of the
      depleted reserve pool. However, to fully account for the slower recovery of
      depression, a decrease in the rate constant of vesicle mobilization from the
      reserve pool of about sixfold is also required.

PMID- 9635755
TI  - Intensive extrusion and occlusion of water in ganglioside micelles with thermal
      reversibility.
AB  - By using a shell-modeling analysis for small-angle scattering data of ganglioside
      micellar dispersion, we recently reported that the elevation of temperature
      induces a significant shrinkage of the hydrophilic region of the ganglioside
      micelle, suggesting that the oligosaccharide chains with sialic acid residues of
      ganglioside molecules change the conformation, sensitively responding to a change
      in temperature (Hirai et al., 1996. Biophys. J. 70:1761-1768; J. Phys. Chem.
      100:11675-11680). We have carried out further analyses of the temperature
      dependence of the structural parameters reported previously, and we have found
      clear evidence of reversible extrusion and occlusion of a large amount of water
      in the hydrophilic region of the ganglioside micelle in the physiological
      temperature range of 6-60 degrees C. The present results suggest a remarkable
      function of ganglioside molecules: they change the hydrophilicity of the cell
      surface locally as a response to variations in temperature. This phenomenon might
      be involved in various surface events, such as cell-cell interaction and cell
      surface-protein interaction.

PMID- 9635756
TI  - Control by osmotic pressure of voltage-induced permeabilization and gene transfer
      in mammalian cells.
AB  - Cells can be transiently permeabilized by a membrane potential difference
      increase induced by the application of high electric pulses. This was shown to be
      under the control of the pulsing buffer osmotic pressure, when short pulses were
      applied. In this paper, the effects of buffer osmotic pressure during electric
      treatment and during the following 10 min were investigated in Chinese hamster
      ovary cells subjected to long (ms) square wave pulses, a condition needed to
      mediate gene transfer. No effect on cell permeabilization for a small molecule
      such as propidium iodide was observed. The use of a hypoosmolar buffer during
      pulsation allows more efficient loading of cells with beta-galactosidase, a
      tetrameric protein, but no effect of the postpulse buffer osmolarity was
      observed. The resulting expression of plasmid coding for beta-galactosidase was
      strongly controlled by buffer osmolarity during as well as after the pulse. The
      results, tentatively explained in terms of the effect of osmotic pressure on cell
      swelling, membrane organization, and interaction between molecules and membrane,
      support the existence of key steps in plasmid-membrane interaction in the
      mechanism of cell electrically mediated gene transfer.

PMID- 9635757
TI  - Structural features that modulate the transmembrane migration of a hydrophobic
      peptide in lipid vesicles.
AB  - Two approaches employing nuclear magnetic resonance (NMR) were used to
      investigate the transmembrane migration rate of the C-terminal end of native
      alamethicin and a more hydrophobic analog called L1. Native alamethicin exhibits
      a very slow transmembrane migration rate when bound to phosphatidylcholine
      vesicles, which is no greater than 1 x 10(-4) min(-1). This rate is much slower
      than expected, based on the hydrophobic partition energies of the amino acid side
      chains and the backbone of the exposed C-terminal end of alamethicin. The
      alamethicin analog L1 exhibits crossing rates that are at least 1000 times faster
      than that of native alamethicin. A comparison of the equilibrium positions of
      these two peptides shows that L1 sits approximately 3-4 A deeper in the membrane
      than does native alamethicin (Barranger-Mathys and Cafiso. 1996. Biochemistry.
      35:489). The slow rate of alamethicin crossing can be explained if the peptide
      helix is irregular at its C-terminus and hydrogen bonded to solvent or lipid. We
      postulate that L1 does not experience as large a barrier to transport because its
      C-terminus is already buried within the membrane interface. This difference is
      most easily explained by conformational differences between L1 and alamethicin
      rather than differences in hydrophobicity. The results obtained here demonstrate
      that side-chain hydrophobicity alone cannot account for the energy barriers to
      peptide and protein transport across membranes.

PMID- 9635758
TI  - Interaction of lipophilic ions with the plasma membrane of mammalian cells
      studies by electrorotation.
AB  - The electrical properties of biological and artificial membranes were studied in
      the presence of a number of negatively charged tungsten carbonyl complexes, such
      as [W(CO)5(CN)]- , [W(CO)5(NCS)]-, [W2(CO)10(CN)]-, and [W(CO)5(SCH2C6H5)]-,
      using the single-cell electrorotation and the charge-pulse relaxation techniques.
      Most of the negatively charged tungsten complexes were able to introduce mobile
      charges into the membranes, as judged from electrorotation spectra and relaxation
      experiments. This means that the tungsten derivatives act as lipophilic anions.
      They greatly contributed to the polarizability of the membranes and led to a
      marked dielectric dispersion (frequency dependence of the membrane capacitance
      and conductance). The increment and characteristic frequency of the dispersion
      reflect the structure, environment, and mobility of the charged probe molecule in
      electrorotation experiments with biological membranes. The partition coefficients
      and the translocation rate constants derived from the electrorotation spectra of
      cells agreed well with the corresponding data obtained from charge-pulse
      experiments on artificial lipid bilayers.

PMID- 9635759
TI  - ATP analogs and muscle contraction: mechanics and kinetics of nucleoside
      triphosphate binding and hydrolysis.
AB  - The mechanical behavior of skinned rabbit psoas muscle fiber contractions and in
      vitro motility of F-actin (Vf) have been examined using ATP, CTP, UTP, or their 2
      deoxy forms (collectively designated as nucleotide triphosphates or NTPs) as
      contractile substrates. Measurements of actin-activated heavy meromyosin (HMM)
      NTPase, the rates of NTP binding to myosin and actomyosin, NTP-mediated acto-HMM
      dissociation, and NTP hydrolysis by acto-HMM were made for comparison to the
      mechanical results. The data suggest a very similar mechanism of acto-HMM NTP
      hydrolysis. Whereas all NTPs studied support force production and stiffness that
      vary by a factor 2 or less, the unloaded shortening velocity (Vu) of muscle
      fibers varies by almost 10-fold. 2-Deoxy ATP (dATP) was unique in that Vu was 30%
      greater than with ATP. Parallel behavior was observed between Vf and the steady
      state maximum actin-activated HMM ATPase rate. Further comparisons suggest that
      the variation in force correlates with the rate and equilibrium constant for NTP
      cleavage; the variations in Vu or Vf are related to the rate of cross-bridge
      dissociation caused by NTP binding or to the rate(s) of product release.

PMID- 9635760
TI  - The effect of ATP analogs on posthydrolytic and force development steps in
      skinned skeletal muscle fibers.
AB  - ATP, 2-deoxy ATP (dATP), CTP, and UTP support isometric force and unloaded
      shortening velocity (Vu) to various extents (Regnier et al., Biophys. J. 74:3044
      3058). Vu correlated with the rate of cross-bridge dissociation after the power
      stroke and the steady-state hydrolysis rate in solution, whereas force was
      modulated by NTP binding and cleavage. Here we studied the influence of
      posthydrolytic cross-bridge steps on force and fiber shortening by measuring
      isometric force and stiffness, the rate of tension decline (kPi) after Pi
      photogeneration from caged Pi, and the rate of tension redevelopment (ktr) after
      a sudden release and restretch of fibers. The slope of the force versus [Pi]
      relationship was the same for ATP, dATP, and CTP, but for UTP it was threefold
      less. ktr and kPi increased with increasing [Pi] with a similar slope for ATP,
      dATP, and CTP, but had an increasing magnitude of the relationship ATP < dATP <
      CTP. UTP reduced ktr but increased kPi. The results suggest that the rate
      constant for the force-generating isomerization increases with the order ATP <
      dATP < CTP < UTP. Simulations using a six-state model suggest that increasing the
      force-generating rate accounts for the faster kPi in dATP, CTP, and UTP. In
      contrast, ktr appears to be strongly affected by the rates of NTP binding and
      cleavage and the rate of the force-generating isomerization.

PMID- 9635761
TI  - Characterizations of cross-bridges in the presence of saturating concentrations
      of MgAMP-PNP in rabbit permeabilized psoas muscle.
AB  - Several earlier studies have led to different conclusions about the complex of
      myosin with MgAMP-PNP. It has been suggested that subfragment 1 of myosin (S1)
      MgAMP-PNP forms an S1-MgADP-like state, an intermediate between the myosin S1
      MgATP and myosin S1-MgADP states or a mixture of cross-bridge states. We suggest
      that the different states observed result from the failure to saturate S1 with
      MgAMP-PNP. At saturating MgAMP-PNP, the interaction of myosin S1 with actin is
      very similar to that which occurs in the presence of MgATP. 1) At 1 degrees C and
      170 mM ionic strength the equatorial x-ray diffraction intensity ratio I11/I10
      decreased with an increasing MgAMP-PNP concentration and leveled off by
      approximately 20 mM MgAMP-PNP. The resulting ratio was the same for MgATP-relaxed
      fibers. 2) The two dimensional x-ray diffraction patterns from MgATP-relaxed and
      MgAMP-PNP-relaxed bundles are similar. 3) The affinity of S1-MgAMP-PNP for the
      actin-tropomyosin-troponin complex in solution in the absence of free calcium is
      comparable with that of S1-MgATP. 4) In the presence of calcium, I11/I10
      decreased toward the relaxed value with increasing MgAMP-PNP, signifying that the
      affinity between cross-bridge and actin is weakened by MgAMP-PNP. 5) The degree
      to which the equatorial intensity ratio decreases as the ionic strength increases
      is similar in MgAMP-PNP and MgATP. Therefore, results from both fiber and
      solution studies suggest that MgAMP-PNP acts as a non hydrolyzable MgATP analogue
      for myosin.

PMID- 9635762
TI  - Steady-state fluorescence polarization studies of the orientation of myosin
      regulatory light chains in single skeletal muscle fibers using pure isomers of
      iodoacetamidotetramethylrhodamine.
AB  - The regulatory light chain (RLC) from chicken gizzard myosin was covalently
      modified on cysteine 108 with either the 5- or 6-isomer of
      iodoacetamidotetramethylrhodamine (IATR). Labeled RLCs were purified by fast
      protein liquid chromatography and characterized by reverse-phase high-performance
      liquid chromatography (HPLC), tryptic digestion, and electrospray mass
      spectrometry. Labeled RLCs were exchanged into the native myosin heads of single
      skinned fibers from rabbit psoas muscle, and the ATR dipole orientations were
      determined by fluorescence polarization. The 5- and 6-ATR dipoles had distinct
      orientations, and model orientational distributions suggest that they are more
      than 20 degrees apart in rigor. In the rigor-to-relaxed transition (sarcomere
      length 2.4 microm, 10 degrees C), the 5-ATR dipole became more perpendicular to
      the fiber axis, but the 6-ATR dipole became more parallel. This orientation
      change was absent at sarcomere length 4.0 microm, where overlap between myosin
      and actin filaments is abolished. When the temperature of relaxed fibers was
      raised to 30 degrees C, the 6-ATR dipoles became more parallel to the fiber axis
      and less ordered; when ionic strength was lowered from 160 mM to 20 mM (5 degrees
      C), the 6-ATR dipoles became more perpendicular to the fiber axis and more
      ordered. In active contraction (10 degrees C), the orientational distribution of
      the probe dipoles was similar but not identical to that in relaxation, and was
      not a linear combination of the orientational distributions in relaxation and
      rigor.

PMID- 9635763
TI  - Fluorescence polarization transients from rhodamine isomers on the myosin
      regulatory light chain in skeletal muscle fibers.
AB  - Fluorescence polarization was used to examine orientation changes of two
      rhodamine probes bound to myosin heads in skeletal muscle fibers. Chicken gizzard
      myosin regulatory light chain (RLC) was labeled at Cys108 with either the 5- or
      the 6-isomer of iodoacetamidotetramethylrhodamine (IATR). Labeled RLC (termed
      Cys108-5 or Cys108-6) was exchanged for the endogenous RLC in single, skinned
      fibers from rabbit psoas muscle. Three independent fluorescence polarization
      ratios were used to determine the static angular distribution of the probe
      dipoles with respect to the fiber axis and the extent of probe motions on the
      nanosecond time scale of the fluorescence lifetime. We used step changes in fiber
      length to partially synchronize the transitions between biochemical, structural,
      and mechanical states of the myosin cross-bridges. Releases during active
      contraction tilted the Cys108-6 dipoles away from the fiber axis. This response
      saturated for releases beyond 3 nm/half-sarcomere (h.s.). Stretches in active
      contraction caused the dipoles to tilt toward the fiber axis, with no evidence of
      saturation for stretches up to 7 nm/h.s. These nonlinearities of the response to
      length changes are consistent with a partition of approximately 90% of the probes
      that did not tilt when length changes were applied and 10% of the probes that
      tilted. The responding fraction tilted approximately 30 degrees for a 7.5 nm/h.s.
      release and traversed the plane perpendicular to the fiber axis for larger
      releases. Stretches in rigor tilted Cys108-6 dipoles away from the fiber axis,
      which was the opposite of the response in active contraction. The transition from
      the rigor-type to the active-type response to stretch preceded the main force
      development when fibers were activated from rigor by photolysis of caged ATP in
      the presence of Ca2+. Polarization ratios for Cys108-6 in low ionic strength (20
      mM) relaxing solution were compatible with a combination of the relaxed (200 mM
      ionic strength) and rigor intensities, but the response to length changes was of
      the active type. The nanosecond motions of the Cys108-6 dipole were restricted to
      a cone of approximately 20 degrees half-angle, and those of Cys108-5 dipole to a
      cone of approximately 25 degrees half-angle. These values changed little between
      relaxation, active contraction, and rigor. Cys108-5 showed very small-amplitude
      tilting toward the fiber axis for both stretches and releases in active
      contraction, but much larger amplitude tilting in rigor. The marked differences
      in these responses to length steps between the two probe isomers and between
      active contraction and rigor suggest that the RLC undergoes a large angle change
      (approximately 60 degrees) between these two states. This motion is likely to be
      a combination of tilting of the RLC relative to the fiber axis and twisting of
      the RLC about its own axis.

PMID- 9635764
TI  - Localization of Cys133 of rabbit skeletal troponin-I with respect to troponin-C
      by resonance energy transfer.
AB  - We have used the technique of resonance energy transfer in conjunction with
      distance geometry analysis to localize Cys133 of troponin-I (TnI) with respect to
      troponin-C (TnC) in the ternary troponin complex and the binary TnC.TnI complex
      in the presence and absence of Ca2+. Cys133 of TnI was chosen because our
      previous work has shown that the region of TnI containing this residue undergoes
      Ca2+-dependent movements between actin and TnC, and may play an important role in
      the regulatory function of troponin. For this purpose, a TnI mutant with a single
      Cys at position 133, and TnC mutants, each with a single Cys at positions 5, 12,
      21, 41, 49, 89, 98, 133, and 158, were constructed by site-directed mutagenesis.
      The distances between TnI Cys133 and each of the nine residues in TnC were then
      measured. Using a least-squares minimization procedure, we determined the
      position of TnI Cys133 in the coordinate system of the crystal structure of TnC.
      Our results show that in the presence of Ca2+, TnI Cys133 is located near residue
      12 beneath the N-terminal lobe of TnC, and moves away by 12.6 A upon the removal
      of Ca2+. TnI Cys133 and the region of TnC that undergoes major change in
      conformation in response to Ca2+ are located roughly on opposite sides of TnC's
      central helix. This suggests that the region in TnI that undergoes Ca2+-dependent
      interaction with TnC is distinct from that interacting with actin.

PMID- 9635766
TI  - Molecular mechanics studies on the conformations of 2',3'-dideoxy-2',3'
      didehydroguanine nucleoside, D4G.
AB  - Conformational energy calculations have been presented on guanine nucleoside in
      which the furanose ring is replaced by 2',3'-dideoxy-2',3'-didehydrofuran using
      molecular mechanics and conformational analysis. Conformational energies have
      been evaluated using the MM2 and AMBER94 force field parameters at two different
      dielectric constants. The results are presented in terms of isoenergy contours in
      the conformational space of the glycosidic (chi) and C4'-C5' (gamma) bonds
      torsions. In general, the chi-gamma interrelationships differ from the
      corresponding plots for unmodified nucleosides and nucleotides, reported
      previously. Consistency of the calculated preferred conformations with the x-ray
      data is sensitive to the force field employed.

PMID- 9635765
TI  - ATPase and shortening rates in frog fast skeletal myofibrils by time-resolved
      measurements of protein-bound and free Pi.
AB  - Shortening and ATPase rates were measured in Ca2+-activated myofibrils from frog
      fast muscles in unloaded conditions at 4 degrees C. ATPase rates were determined
      using the phosphate-binding protein method (free phosphate) and quench flow
      (total phosphate). Shortening rates at near zero load (V0) were estimated by
      quenching reaction mixtures 50 ms to 10 s old at pH 3.5 and measuring sarcomere
      lengths under the optical microscope. As with the rabbit psoas myofibrils (C.
      Lionne, F. Travers, and T. Barman, 1996, Biophys. J. 70:887-895), the ATPase
      progress curves had three phases: a transient Pi burst, a fast linear phase (kF),
      and a deceleration to a slow phase (kS). Evidence is given that kF is the ATPase
      rate of shortening myofibrils. V0 is in good agreement with mechanical
      measurements in myofibrils and fibers. Under the same conditions and at
      saturation in ATP, V0 and kF are 2.4 microm half-sarcomere(-1) s(-1) and 4.6 s(
      1), and their Km values are 33 and 200 microM, respectively. These parameters are
      higher than found with rabbit psoas myofibrils. The myofibrillar kF is higher
      than the fiber ATPase rates obtained previously in frog fast muscles but
      considerably lower than obtained in skinned fibers by the phosphate-binding
      protein method (Z. H. He, R. K. Chillingworth, M. Brune, J. E. T. Corrie, D. R.
      Trentham, M. R. Webb, and M. R. Ferenczi, 1997, J. Physiol. 50:125-148). We show
      that, with frog as with rabbit myofibrillar ATPase, phosphate release is the rate
      limiting step.

PMID- 9635767
TI  - Effects of supercoiling in electrophoretic trapping of circular DNA in
      polyacrylamide gels.
AB  - Electrophoretic velocity and orientation have been used to study the electric
      field-induced trapping of supercoiled and relaxed circular DNA (2926 and 5386 bp)
      in polyacrylamide gels (5% T, 3.3% C) at 7.5-22.5 V/cm, using as controls linear
      molecules of either the same contour length or the same radius of gyration. The
      circle-specific trapping is reversible. From the duration of the reverse pulse
      needed to detrap the molecules, the average trap depth is estimated to be 90 A,
      which is consistent with the molecular charge and the field strengths needed to
      keep molecules trapped. Trapped circles exhibit a strong field alignment compared
      to the linear form, and there is a good correlation between the enhanced field
      alignment for the circles and the onset of trapping in both constant and pulsed
      fields. The circles do not exhibit the orientation overshoot response to a field
      pulse seen with linear DNA, and the rate of orientation growth scales as E(-2+/
      0.1) with the field, as opposed to E(-1.1+/-0.1) for the linear form. These
      results show that the linear form migrates by cyclic reptation, whereas the
      circles most likely are trapped by impalement on gel fibers. This proposal is
      supported by very similar velocity and orientation behavior of circular DNA in
      agarose gels, where impalement has been deemed more likely because of stiffer gel
      fibers. The trapping efficiency is sensitive to DNA topology, as expected for
      impalement. In polyacrylamide the supercoiled form (superhelical density sigma = 
      0.05) has a two- to fourfold lower probability of trapping than the corresponding
      relaxed species, whereas in agarose gels the supercoiled form is not trapped at
      all. These results are consistent with existing data on the average holes in the
      plectonemic supercoiled structures and the fiber thicknesses in the two gel
      types. On the basis of the topology effect, it is argued that impalement during
      pulsed-field electrophoresis in polyacrylamide gels may be useful for the
      separation of more intricate DNA structures such as knots. The results also
      indicate that linear dichroism on field-aligned molecules can be used to measure
      the supercoiling angle, if relaxed DNA circles are used as controls for the
      global degree of orientation.

PMID- 9635768
TI  - DNA bending by small, mobile multivalent cations.
AB  - We propose a purely electrostatic mechanism by which small, mobile, multivalent
      cations can induce DNA bending. A multivalent cation binds at the entrance to the
      B-DNA major groove, between the two phosphate strands, electrostatically
      repelling sodium counterions from the neighboring phosphates. The unscreened
      phosphates on both strands are strongly attracted to the groove-bound cation.
      This leads to groove closure, accompanied by DNA bending toward the cationic
      ligand. We explicitly treat the dynamic character of the cation-DNA interaction
      using an adiabatic approximation, noting that DNA bending is much slower than the
      diffusion of nonspecifically bound, mobile cations. We make semiquantitative
      estimates of the free energy components of bending-electrostatic (with a
      sigmoidal distance-dependent dielectric function), elastic, and entropic cation
      localization-and find that the equilibrium state is bent B-DNA stabilized with a
      self-localized cation. This is a bending polaron, formation of which should be
      critically dependent on the strength of electrostatic interaction and the
      concentration of highly mobile cations available for self-localization. We
      predict that the resultant bend will be large (approximately 20-40 degrees),
      smooth (because it is spread over 6 bp), and infrequent. The stability of such a
      bend can be variable, from transient to highly stable (static) bending,
      observable with standard curvature-measuring techniques. We further predict that
      this bending mechanism will have an unusual sequence dependence: sequences with
      less binding specificity will be more bent, unless the specific binding site is
      in the major groove.

PMID- 9635769
TI  - Tyrosine quenching of tryptophan phosphorescence in glyceraldehyde-3-phosphate
      dehydrogenase from Bacillus stearothermophilus.
AB  - Tyrosine is known to quench the phosphorescence of free tryptophan derivatives in
      solution, but the interaction between tryptophan residues in proteins and
      neighboring tyrosine side chains has not yet been demonstrated. This report
      examines the potential role of Y283 in quenching the phosphorescence emission of
      W310 of glyceraldehyde-3-phosphate dehydrogenase from Bacillus stearothermophilus
      by comparing the phosphorescence characteristics of the wild-type enzyme to that
      of appositely designed mutants in which either the second tryptophan residue,
      W84, is replaced with phenylalanine or Y283 is replaced by valine.
      Phosphorescence spectra and lifetimes in polyol/buffer low-temperature glasses
      demonstrate that W310, in both wild-type and W84F (Trp84-->Phe) mutant proteins,
      is already quenched in viscous low-temperature solutions, before the onset of
      major structural fluctuations in the macromolecule, an anomalous quenching that
      is abolished with the mutation Y283V (Tyr283-->Val). In buffer at ambient
      temperature, the effect of replacing Y283 with valine on the phosphorescence of
      W310 is to lengthen its lifetime from 50 micros to 2.5 ms, a 50-fold enhancement
      that again emphasizes how W310 emission is dominated by the local interaction
      with Y283. Tyr quenching of W310 exhibits a strong temperature dependence, with a
      rate constant kq = 0.1 s(-1) at 140 K and 2 x 10(4) s(-1) at 293 K. Comparison
      between thermal quenching profiles of the W84F mutant in solution and in the dry
      state, where protein flexibility is drastically reduced, shows that the
      activation energy of the quenching reaction is rather small, Ea < or = 0.17 kcal
      mol(-1), and that, on the contrary, structural fluctuations play an important
      role on the effectiveness of Tyr quenching. Various putative quenching mechanisms
      are examined, and the conclusion, based on the present results as well as on the
      phosphorescence characteristics of other protein systems, is that Tyr quenching
      occurs through the formation of an excited-state triplet exciplex.

PMID- 9635770
TI  - Secondary pair charge recombination in photosystem I under strongly reducing
      conditions: temperature dependence and suggested mechanism.
AB  - Photoinduced electron transfer in photosystem I (PS I) proceeds from the excited
      primary electron donor P700 (a chlorophyll a dimer) via the primary acceptor A0
      (chlorophyll a) and the secondary acceptor A1 (phylloquinone) to three [4Fe-4S]
      clusters, Fx, FA, and FB. Prereduction of the iron-sulfur clusters blocks
      electron transfer beyond A1. It has been shown previously that, under such
      conditions, the secondary pair P700+A1- decays by charge recombination with t1/2
      approximately 250 ns at room temperature, forming the P700 triplet state (3P700)
      with a yield exceeding 85%. This reaction is unusual, as the secondary pair in
      other photosynthetic reaction centers recombines much slower and forms directly
      the singlet ground state rather than the triplet state of the primary donor. Here
      we studied the temperature dependence of secondary pair recombination in PS I
      from the cyanobacterium Synechococcus sp. PCC6803, which had been illuminated in
      the presence of dithionite at pH 10 to reduce all three iron-sulfur clusters. The
      reaction P700+A1- --> 3P700 was monitored by flash absorption spectroscopy. With
      decreasing temperature, the recombination slowed down and the yield of 3P700
      decreased. In the range between 303 K and 240 K, the recombination rates could be
      described by the Arrhenius law with an activation energy of approximately 170
      meV. Below 240 K, the temperature dependence became much weaker, and
      recombination to the singlet ground state became the dominating process. To
      explain the fast activated recombination to the P700 triplet state, we suggest a
      mechanism involving efficient singlet to triplet spin evolution in the secondary
      pair, thermally activated repopulation of the more closely spaced primary pair
      P700+A0- in a triplet spin configuration, and subsequent fast recombination
      (intrinsic rate on the order of 10(9) s(-1)) forming 3P700.

PMID- 9635771
TI  - Properties of intramolecular proton transfer in carbonic anhydrase III.
AB  - We investigated the efficiency of glutamic acid 64 and aspartic acid 64 as proton
      donors to the zinc-bound hydroxide in a series of site-specific mutants of human
      carbonic anhydrase III (HCA III). Rate constants for this intramolecular proton
      transfer, a step in the catalyzed dehydration of bicarbonate, were determined
      from the proton-transfer-dependent rates of release of H2 18O from the enzyme
      measured by mass spectrometry. The free energy plots representing these rate
      constants could be fit by the Marcus rate theory, resulting in an intrinsic
      barrier for the proton transfer of deltaG0++ = 2.2 +/- 0.5 kcal/mol, and a work
      function or thermodynamic contribution to the free energy of reaction wr = 10.8
      +/- 0.1 kcal/mol. These values are very similar in magnitude to the Marcus
      parameters describing intramolecular proton transfer from His64 and His67 to the
      zinc-bound hydroxide in mutants of HCA III. That result and the equivalent
      efficiency of Glu64 and Asp64 as proton donors in the catalysis by CA III
      demonstrate a lack of specificity in proton transfer from these sites, which is
      indirect evidence of a number of proton conduction pathways through different
      structures of intervening water chains. The dominance of the thermodynamic
      contribution or work function for all of these proton transfers is consistent
      with the view that formation and breaking of hydrogen bonds in such water chains
      is a limiting factor for proton translocation.

PMID- 9635772
TI  - Site-specific thermodynamics and kinetics of a coiled-coil transition by spin
      inversion transfer NMR.
AB  - A 33-residue pseudo-wild-type GCN4 leucine zipper peptide is used to probe the
      equilibrium conformational population in proteins. 13Calpha-NMR shows that chain
      sites differ in structural content at a given temperature, and that two dimeric
      folded forms are evident at many sites. Spin inversion transfer experiments are
      reported bearing on the thermodynamics and kinetics of interconversion of the two
      dimeric folded forms (Fa <--> Fb) at the 13Calpha-labeled position L13. At each
      temperature, at conditions wherein the population of unfolded chains is quite
      small, inversion of the Fa spins via a tuned Gaussian pi-pulse is followed by a
      time interval (tau), interrogation, and recording of the free induction decay.
      Fifteen such inversions, with varying tau, provide the time course for recovery
      of equilibrium magnetization after inversion. Similar experiments follow
      inversion of the Fb spins. Re-equilibration is known to be modulated by four
      first-order rate constants: two (T1a(-1) and T1b(-1)) for spin-lattice relaxation
      intrinsic to the respective sites, and two (kab and kba) for the conformational
      change. All four follow from joint, Bayesian analysis of all the data at each
      temperature. The equilibrium constant at each temperature for this local
      transition, determined simply from the equilibrium relative magnetizations at Fa
      and Fb sites, agrees well with the kinetic ratio kab/kba. The standard Gibbs
      energies, enthalpy, and entropy follow. Activation parameters, both ways, are
      accessible from the rate constants and suggest a transition state with high Gibbs
      energy and enthalpy, but with entropy between those of Fa and Fb.

PMID- 9635773
TI  - New sterically stabilized vesicles based on nonionic surfactant, cholesterol, and
      poly(ethylene glycol)-cholesterol conjugates.
AB  - Monomethoxypoly(ethylene glycol) cholesteryl carbonates (M-PEG-Chol) with polymer
      chain molecular weights of 1000 (M-PEG1000-Chol) and 2000 (M-PEG2000-Chol) have
      been newly synthesized and characterized. Their aggregation behavior in mixture
      with diglycerol hexadecyl ether (C16G2) and cholesterol has been examined by
      cryotransmission electron microscopy, high-performance gel exclusion
      chromatography, and quasielastic light scattering. Nonaggregated, stable,
      unilamellar vesicles were obtained at low polymer levels with optimal shape and
      size homogeneity at cholesteryl conjugate/ lipids ratios of 10 mol% M-PEG1000
      Chol or 5 mol% M-PEG2000-Chol, corresponding to the theoretically predicted brush
      conformational state of the PEG chains. At 20 mol% M-PEG1000-Chol or 10 mol% M
      PEG2000-Chol, the saturation threshold of the C16G2/cholesterol membrane in
      polymer is exceeded, and open disk-shaped aggregates are seen in coexistence with
      closed vesicles. Higher levels up to 30 mol% lead to the complete solubilization
      of the vesicles into disk-like structures of decreasing size with increasing PEG
      content. This study underlines the bivalent role of M-PEG-Chol derivatives: while
      behaving as solubilizing surfactants, they provide an efficient steric barrier,
      preventing the vesicles from aggregation and fusion over a period of at least 2
      weeks.

PMID- 9635774
TI  - Fibrous long spacing collagen ultrastructure elucidated by atomic force
      microscopy.
AB  - Fibrous long spacing collagen (FLS) fibrils are collagen fibrils in which the
      periodicity is clearly greater than the 67-nm periodicity of native collagen. FLS
      fibrils were formed in vitro by the addition of alpha1-acid glycoprotein to an
      acidified solution of monomeric collagen and were imaged with atomic force
      microscopy. The fibrils formed were typically approximately 150 nm in diameter
      and had a distinct banding pattern with a 250-nm periodicity. At higher
      resolution, the mature FLS fibrils showed ultrastructure, both on the bands and
      in the interband region, which appears as protofibrils aligned along the main
      fibril axis. The alignment of protofibrils produced grooves along the main
      fibril, which were 2 nm deep and 20 nm in width. Examination of the tips of FLS
      fibrils suggests that they grow via the merging of protofibrils to the tip,
      followed by the entanglement and, ultimately, the tight packing of protofibrils.
      A comparison is made with native collagen in terms of structure and mechanism of
      assembly.

PMID- 9635775
TI  - Orientations of tyrosines 21 and 24 in coat subunits of Ff filamentous virus:
      determination by Raman linear intensity difference spectroscopy and implications
      for subunit packing.
AB  - Virions of the Ff group of bacteriophages (fd, f1, M13) are morphologically
      identical filaments (approximately 6-nm diameter x approximately 880-nm length)
      in which a covalently closed, single-stranded DNA genome is sheathed by
      approximately 2700 copies of a 50-residue alpha-helical subunit (pVIII).
      Orientations of pVIII tyrosines (Tyr21 and Tyr24) with respect to the filament
      axis have been determined by Raman linear intensity difference (RLID)
      spectroscopy of flow-oriented mutant virions in which the tyrosines were
      independently mutated to methionine. The results show that the twofold axis of
      the phenolic ring (C1-C4 line) of Tyr21 is inclined at 39.5 +/- 1.4 degrees from
      the virion axis, and that of Tyr24 is inclined at 43.7 +/- 0.6 degrees. The
      orientation determined for the Tyr21 phenol ring is close to that of a structural
      model previously proposed on the basis of fiber x-ray diffraction results
      (Protein Data Bank, identification code 1IFJ). On the other hand, the orientation
      determined for the Tyr24 phenol ring differs from the diffraction-based model by
      a 40 degrees rotation about the Calpha-Cbeta bond. The RLID results also indicate
      that each tyrosine mutation does not greatly affect the orientation of either the
      remaining tyrosine or single tryptophan (Trp26) of pVIII. On the basis of these
      results, a refined model is proposed for the coat protein structure in Ff.

PMID- 9635776
TI  - Effects of temperature and deltaGo on electron transfer from cytochrome c2 to the
      photosynthetic reaction center of the purple bacterium Rhodobacter sphaeroides.
AB  - The kinetics of electron transfer from cytochrome c2 to the primary donor (P) of
      the reaction center from the photosynthetic purple bacterium Rhodobacter
      sphaeroides have been investigated by time-resolved absorption spectroscopy.
      Rereduction of P+ induced by a laser pulse has been measured at temperatures from
      300 K to 220 K in a series of specifically mutated reaction centers characterized
      by altered midpoint redox potentials of P+/P varying from 410 mV to 765 mV (as
      compared to 505 mV for wild type). Rate constants for first-order electron
      donation within preformed reaction center-cytochrome c2 complexes and for the
      bimolecular oxidation of free cytochrome c2 have been obtained by
      multiexponential deconvolution of the kinetics. At all temperatures the rate of
      the fastest intracomplex electron transfer increases by more than two orders of
      magnitude as the driving force -deltaGo is varied over a range of 350 meV. The
      temperature and deltaGo dependences of the rate constant fit the Marcus equation
      well. Global analysis yields a reorganization energy lambda = 0.96 +/- 0.07 eV
      and a set of electronic matrix elements, specific for each mutant, ranging from
      1.2 10(-4) eV to 2.5 10(-4) eV. Analysis in terms of the Jortner equation
      indicates that the best fit is obtained in the classical limit and restricts the
      range of coupled vibrational modes to frequencies lower than approximately 200
      cm(-1). An additional slower kinetic component of P+ reduction, attributed to
      electron transfer from cyt c2 docked in a nonoptimal configuration of the
      complex, displays a Marcus type dependence of the rate constant upon deltaGo,
      characterized by a similar value of lambda (0.8 +/- 0.1 eV) and by an average
      electronic matrix element smaller by more than one order of magnitude. In all of
      the mutants, as the temperature is decreased below 260 K, both intracomplex
      reactions are abruptly inhibited, their rate being negligible at 220 K. The free
      energy dependence of the second-order rate constant for oxidation of cyt c2 in
      solution suggests that the collisional reaction is partially diffusion
      controlled, reaching the diffusion limit at exothermicities between 150 and 250
      meV over the temperature range investigated.

PMID- 9635777
TI  - Fatty acid-induced alteration of the porphyrin macrocycle of cytochrome P450 BM3.
AB  - Surface-enhanced resonance Raman scattering (SERRS) of substrate-free and
      substrate-bound forms of the P450 domain of cytochrome P450 BM3 are reported and
      assigned. Substrate-free P450 yields mixed spin heme species in which the
      pentacoordinate high-spin arrangement is dominant. The addition of laurate or
      palmitate leads to an increase in high spin content and to an allosteric
      activation of heme mode v29, which is sensitive to peripheral heme/protein
      interactions. Differences between laurate and palmitate binding are observed in
      the relative intensities of a number of bands and the splitting of the heme vinyl
      modes. Laurate binding to P450 results in different protein environments being
      experienced by each vinyl mode, whereas palmitate binding produces a smaller
      difference. The results demonstrate the ability of SERRS to probe
      substrate/prosthetic group interactions within an active site, at low protein
      concentrations.

PMID- 9635778
TI  - Resonance Raman microspectroscopy of myeloperoxidase and cytochrome b558 in human
      neutrophilic granulocytes.
AB  - With (resonance) Raman microscospectroscopy, it is possible to investigate the
      chemical constitution of a very small volume (0.5 fl) in a living cell. We have
      measured resonance Raman spectra in the cytoplasm of living normal,
      myeloperoxidase (MPO)-deficient, and cytochrome b558-deficient neutrophils and in
      isolated specific and azurophilic granule fractions, using an excitation
      wavelength of 413.1 nm. Similar experiments were performed after reduction of the
      redox centers by the addition of sodium dithionite. The specific and azurophilic
      granules in both redox states appeared to have clearly distinguishable Raman
      spectra when exciting at a wavelength of 413.1 nm. The azurophilic granules and
      the cytochrome b558-deficient neutrophils showed Raman spectra similar to that of
      the isolated MPO. The spectra of the specific granules and the MPO-deficient
      neutrophils corresponded very well to published cytochrome b558 spectra. The
      resonance Raman spectrum of the cytoplasmic region of normal neutrophilic
      granulocytes could be fitted with a combination of the spectra of the specific
      and azurophilic granules, which shows that the Raman signal of neutrophilic
      granulocytes mainly originates from MPO and cytochrome b558, at an excitation
      wavelength of 413.1 nm.

PMID- 9635779
TI  - Atomic force microscopy detects changes in the interaction forces between GroEL
      and substrate proteins.
AB  - The structure of the Escherichia coli chaperonin GroEL has been investigated by
      tapping-mode atomic force microscopy (AFM) under liquid. High-resolution images
      can be obtained, which show the up-right position of GroEL adsorbed on mica with
      the substrate-binding site on top. Because of this orientation, the interaction
      between GroEL and two substrate proteins, citrate synthase from Saccharomyces
      cerevisiae with a destabilizing Gly-->Ala mutation and RTEM beta-lactamase from
      Escherichia coli with two Cys-->Ala mutations, could be studied by force
      spectroscopy under different conditions. The results show that the interaction
      force decreases in the presence of ATP (but not of ATPgammaS) and that the force
      is smaller for native-like proteins than for the fully denatured ones. It also
      demonstrates that the interaction energy with GroEL increases with increasing
      molecular weight. By measuring the interaction force changes between the
      chaperonin and the two different substrate proteins, we could specifically detect
      GroEL conformational changes upon nucleotide binding.

PMID- 9635780
TI  - Vesicle size distributions measured by flow field-flow fractionation coupled with
      multiangle light scattering.
AB  - The separation method, flow field-flow fractionation (flow FFF), is coupled on
      line with multiangle laser light scattering (MALLS) for simultaneous measurement
      of the size and concentration of vesicles eluting continuously from the
      fractionator. These size and concentration data, gathered as a function of
      elution time, may be used to construct both number- and mass-weighted vesicle
      size distributions. Unlike most competing, noninvasive methods, this flow
      FFF/MALLS technique enables measurement of vesicle size distributions without a
      separate refractive index detector, calibration using particle size standards, or
      prior assumptions about the shape of the size distribution. Experimentally
      measured size distributions of vesicles formed by extrusion and detergent removal
      are non-Gaussian and are fit well by the Weibull distribution. Flow FFF/MALLS
      reveals that both the extrusion and detergent dialysis vesicle formation methods
      can yield nearly size monodisperse populations with standard deviations of
      approximately 8% about the mean diameter. In contrast to the rather low
      resolution of dynamic light scattering in analyzing bimodal systems, flow
      FFF/MALLS is shown to resolve vesicle subpopulations that differ by much less
      than a factor of two in mean size.

PMID- 9635781
TI  - Domain structure and molecular conformation in annexin V/1,2-dimyristoyl-sn
      glycero-3-phosphate/Ca2+ aqueous monolayers: a Brewster angle microscopy/infrared
      reflection-absorption spectroscopy study.
AB  - Annexins comprise a family of proteins that exhibit a Ca2+-dependent binding to
      phospholipid membranes that is possibly relevant to their in vivo function.
      Although substantial structural information about the ternary
      (protein/lipid/Ca2+) interaction in bulk phases has been derived from a variety
      of techniques, little is known about the temporal and spatial organization of
      ternary monolayer films. The effect of Ca2+ on the interactions between annexin V
      (AxV) and anionic DMPA monolayers was therefore investigated using three
      complementary approaches: surface pressure measurements, infrared reflection
      absorption spectroscopy (IRRAS), and Brewster angle microscopy (BAM). In the
      absence of Ca2+, the injection of AxV into an aqueous subphase beneath a DMPA
      monolayer initially in a liquid expanded phase produced BAM images revealing
      domains of protein presumably surrounded by liquid-expanded lipid. The protein
      rich areas expanded with time, resulting in reduction of the area available to
      the DMPA and, eventually, in the formation of condensed lipid domains in spatial
      regions separate from the protein film. There was thus no evidence for a specific
      binary AxV/lipid interaction. In contrast, injection of AxV/Ca2+ at a total Ca2+
      concentration of 10 microM beneath a DMPA monolayer revealed no pure protein
      domains, but rather the slow formation of pinhead structures. This was followed
      by slow (>2 h) rigidification of the whole film accompanied by an increase in
      surface pressure, and connection of solid domains to form a structure resembling
      strings of pearls. These changes were characteristic of this specific ternary
      interaction. Acyl chain conformational order of the DMPA, as measured by
      nu(sym)CH2 near 2850 cm(-1), was increased in both the AxV/DMPA and AxV/DMPA/Ca2+
      monolayers compared to either DMPA monolayers alone or in the presence of Ca2+.
      The utility of the combined structural and temporal information derived from
      these three complementary techniques for the study of monolayers in situ at the
      air/water interface is evident from this work.

PMID- 9635782
TI  - Passive mechanical behavior of human neutrophils: effects of colchicine and
      paclitaxel.
AB  - The role of microtubules in determining the mechanical rigidity of neutrophils
      was assessed. Neutrophils were treated with colchicine to disrupt microtubules,
      or with paclitaxel to promote formation of microtubules. Paclitaxel caused an
      increase in the number of microtubules in the cells as assessed by
      immunofluorescence, but it had no effect on the presence or organization of actin
      filaments or on cellular mechanical properties. Colchicine at concentrations <1.0
      microM caused disruption of microtubular structures, but had little effect on
      either F-actin or on cellular mechanical properties. Higher concentrations of
      colchicine disrupted microtubular structure, but also caused increased actin
      polymerization and increases in cell rigidity. Treatment with 10 microM
      colchicine increased F-actin content by 17%, the characteristic cellular
      viscosity by 30%, the dependence of viscosity on shear rate by 10%, and the
      cortical tension by 18%. At 100 microM colchicine the corresponding increases
      were F-actin, 25%; characteristic viscosity, 50%; dependence of viscosity on
      shear rate, 20%; and cortical tension, 21%. These results indicate that
      microtubules have little influence on the mechanical properties of neutrophils,
      and that increases in cellular rigidity caused by high concentrations of
      colchicine are due to a secondary effect that triggers actin polymerization. This
      study supports the conclusion that actin filaments are the primary structural
      determinants of neutrophil mechanical properties.

PMID- 9635783
TI  - Flow resistance and drag forces due to multiple adherent leukocytes in
      postcapillary vessels.
AB  - Computational fluid dynamics was used to model flow past multiple adherent
      leukocytes in postcapillary size vessels. A finite-element package was used to
      solve the Navier-Stokes equations for low Reynolds number flow of a Newtonian
      fluid past spheres adhering to the wall of a cylindrical vessel. We determined
      the effects of sphere number, relative geometry, and spacing on the flow
      resistance in the vessel and the fluid flow drag force acting to sweep the sphere
      off the vessel wall. The computations show that when adherent leukocytes are
      aligned on the same side of the vessel, the drag force on each of the interacting
      leukocytes is less than the drag force on an isolated adherent leukocyte and can
      decrease by up to 50%. The magnitude of the reduction depends on the ratio of
      leukocyte to blood vessel diameter and distance between adherent leukocytes.
      However, there is an increase in the drag force when leukocytes adhere to
      opposite sides of the vessel wall. The increase in resistance generated by
      adherent leukocytes in vessels of various sizes is calculated from the
      computational results. The resistance increases with decreasing vessel size and
      is most pronounced when leukocytes adhere to opposite sides of the vessel.

PMID- 9635784
TI  - Diffusion coefficients in the lateral intercellular spaces of Madin-Darby canine
      kidney cell epithelium determined with caged compounds.
AB  - The diffusion coefficients of two caged fluorescent dyes were measured in free
      solution and in the lateral intercellular spaces (LIS) of cultured Madin-Darby
      canine kidney (MDCK) cells after photoactivation by illumination with a
      continuous or pulsed UV laser. Both quantitative video imaging and a new
      photometric method were utilized to determine the rates of diffusion of the caged
      fluorescent dyes: 8-((4,5-dimethoxy-2-nitrobenzyl)oxy)pyrene-1,3,6-trisulfonic
      acid (DMNB-HPTS) and (4,5-dimethoxy-2-nitrobenzyl) fluorescein dextran (10,000
      MW) (DMNB-caged fluorescein dextran). The diffusion coefficients at 37 degrees C
      in free solution were 3.3 x 10(-6) cm2/s (HPTS) and 0.98 x 10(-6) cm2/s (10,000
      MW dextran). Diffusion of HPTS within nominally linear stretches of the LIS of
      MDCK cells grown on glass coverslips was indistinguishable from that in free
      solution, whereas dextran showed a 1.6 +/- 0.5-fold reduction in diffusivity.
      Measurements of HPTS diffusion within the LIS of multicellular regions also
      exhibited a diffusivity comparable to the free solution value. The restriction to
      diffusion of the dextran within the LIS may be due to molecular hindrance.

PMID- 9635785
TI  - Reinnervation after nerve suture in rat groin flaps.
AB  - Regeneration of sensory and adrenergic nerves in the skin was studied in rats.
      The aim was to investigate the effect of reanastomosing the cut nerve ends of the
      nerve trunk leading to the microvascular groin flap. Reinnervation was
      demonstrated immunohistochemically using calcitonin gene-related peptide (CGRP)
      as marker for sensory nerves, neuropeptide Y (NPY) and tyrosine hydroxylase (TH)
      as markers for adrenergic nerves and Protein Gene Product 9.5 (PGP 9.5) as
      general neuronal marker. It was demonstrated that reanastomosing of the nerve
      trunk was favourable for both the sensory and sympathetic reinnervation of
      microsurgical flaps.

PMID- 9635786
TI  - New technique of complete thymectomy in adult rats without tracheal intubation.
AB  - Adult rat thymectomy is frequently performed as part of the protocol for
      experiments in transplant immunology. Current methods used are either imprecise
      (suction methods) or require tracheal intubation (surgical technique) and are
      thus difficult to master. We have developed a safe technique of surgical removal
      of the thymus with resolution of any pneumothorax by suction through the xyphoid
      insertions of the diaphragm. This method is easy to learn and gives a 95% success
      rate.

PMID- 9635787
TI  - Nerve regeneration in diabetic rats.
AB  - This study evaluated the capacity of diabetic rats to recover the ability to walk
      after nerve repair or nerve graft of the posterior tibial nerve at thigh level.
      Functional recovery of the posterior tibial nerve was evaluated by walking track
      analysis during regeneration in streptozotocin-induced diabetic rats. Surgical
      procedures were performed 8 weeks after induction of diabetes. The nerve repair
      was epineurial. The nerve graft was a 1.5 cm segment orthotopically replaced.
      There was no significant difference in functional recovery between normal and
      diabetic rats for both the nerve repair and nerve graft groups at 6, 12, and 24
      weeks after nerve reconstruction. It is concluded that the presence of diabetes
      is not a contraindication for nerve reconstruction.

PMID- 9635788
TI  - Technical details for safer venous and biliary anastomoses for liver
      transplantation in the rat.
AB  - Although orthotopic liver transplantation in the rat is a well-established
      experimental model, no detailed illustrated description of the procedure is
      available in the literature. As a result, achieving success in the technique
      without prolonged learning time requires training in specialized centers where
      the step-by-step details essential to success in the technique can be learnt. The
      aim of this paper is to provide beginners with the culminative experience of 15
      years of improvements made to Kamada's original model, clearly illustrating the
      necessary steps and fine detail of each anastomosis to help beginners avoid
      unnecessary complications. We hope that this complete description of orthotopic
      liver transplantation in the rat, which remains the most difficult rodent
      transplant model to master, will greatly help microsurgeons acquire this
      demanding procedure.

PMID- 9635789
TI  - Developing a standardized test for the assessment of suturing skill in novice
      microsurgeons.
AB  - Suturing performance was assessed for 13 novice microsurgeons throughout a 4-5
      day microsurgical training course. Time to complete a suture (from needle
      insertion to completion of tie-off) was assessed on a standardized suture task,
      for two sutures at the beginning and end of each training day. For days 2-4,
      suturing performance with actual tissue was also assessed at both the beginning
      and end of each day. An average learning curve for suturing performance on the
      standardized test was developed and demonstrated huge performance improvement. A
      consistent and significant relationship existed between trainees' performance on
      the standardized suturing test and suturing of actual tissue. Thus the
      standardized test appears both to reflect actual suturing performance and to be
      sensitive to improvements in suturing skill that result from practice.

PMID- 9635790
TI  - Do leukocytes contribute to impaired microvascular tissue perfusion after
      arterial repair?
AB  - Impaired capillary perfusion may result in flap failure. Platelet emboli,
      polymorphonuclear leukocytes (PMNs), and/or vasospasm have been identified as
      possible causes. This study investigates the role of PMNs in causing impaired
      capillary perfusion in a free flap model. PMN concentrations were depleted using
      antineutrophil serum. The cremaster muscles of 20 Sprague-Dawley rats were
      isolated on a single neurovascular pedicle and after a simulated technically poor
      arterial anastomosis upstream and reperfusion, capillary perfusion was measured
      each hour for 6 hours. Even though the number of PMNs was significantly reduced
      in the animals treated with antineutrophil serum, capillary perfusion was not
      changed compared with controls. These results demonstrate that depleting
      circulating PMNs does not protect capillary perfusion in our model. These
      findings suggest that reduced capillary perfusion downstream from an anastomotic
      repair is not mediated by the presence of PMNs in the microcirculation.

PMID- 9635791
TI  - A comparison by burst testing of three types of vascular anastomosis.
AB  - A new in vivo test for burst strength of arterial anastomoses was tested in 40
      rats. Twelve had a severed right femoral artery reanastomosed by the traditional
      nine-suture technique. In a second group of 12, a modified telescoping sleeve
      method of reanastomosis was used. In a third group of 12, a laser-assisted
      anastomosis using four stay sutures was performed. Four rats had sham procedures.
      Immediately after reanastomosis three vessels from each group plus all four sham
      surgical vessels were subjected to burst testing. These tests were performed
      again on the repaired vessels at 1 week, 1 month, and 2 months. All the vessels
      were patent at burst testing. All repairs held at all times to greater than 160
      mm mean arterial pressure. The four-suture telescopic anastomosis technique was
      consistently strongest over time, but all techniques showed adequate strength at
      all time intervals.

PMID- 9635792
TI  - A simple method of lower extremity arteriography in the rat.

PMID- 9635793
TI  - Functional recovery of transected nerves treated with systemic BDNF and CNTF.
AB  - The purpose of this study was to investigate the effect of systemic co-injections
      of ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor
      (BDNF) on the functional recovery of transected sciatic nerves repaired by
      epineurial coaptation (EC) or collagen tubulization (CT). Forty Sprague-Dawley
      rats underwent transection of their sciatic nerves and repair by either EC or CT.
      With each repair technique, systemic injections of neurotrophic factors or
      control injections of lactated Ringer's solution were given. This resulted in
      four treatment groups: EC, EC + BDNF/CNTF, CT, and CT + BDNF/CNTF. Nerve function
      was assessed using sciatic functional indices (SFI). Animals whose nerves were
      repaired by CT (P = 0.01), CT + BDNF/CNTF (P = 0.04), and EC + BDNF/CNTF (P =
      0.04) all had better functional recovery than those whose nerves were repaired by
      EC. There were no significant differences among these three groups, however.
      Animals in the CT group manifested the most rapid rate of recovery (P = 0.02
      compared with EC). Collagen tubulization and systemic co-injections of BDNF/CNTF
      improve the rate and extent of sciatic functional recovery after nerve repair.
      The improvement in recovery conferred is not additive.

PMID- 9635794
TI  - Surgical technique for vascularized ear transplantation in mice.
AB  - Traditionally, the mouse nonvascularized skin graft has been widely used in organ
      transplant research. There are, however, several limitations with this model, the
      main one being the different immune response of vascularized vs. nonvascularized
      grafts. We have recently developed a vascularized, orthotopic ear transplant
      model in mice. This model has several advantages that make it a useful tool to
      study many aspects of transplantation. The donor operation consists of harvesting
      the ear with intact arterial and venous pedicles. The arterial pedicle is
      dissected down to the common carotid artery with ligation of all branches except
      the auricular artery. The venous pedicle is based on the jugular vein with
      preservation of the auricular veins draining into the posterior facial vein. In
      the subsequent recipient operation, the graft is transplanted into an orthotopic
      position using the common carotid artery for arterial inflow and the jugular vein
      for venous outflow. We performed 16 such transplants (6 isografts, 5 allografts,
      and 5 xenografts), with a success rate of 94% (15/16). The donor operation time
      was 1.5 hours and the recipient operation time was 2.5 hours. The total time for
      anastamosis was 45 +/- 5 minutes. Serial biopsies were obtained on days 3, 5, and
      7, and correlated with gross findings. In summary, this study illustrates that it
      is technically possible to transplant a mouse ear graft. The main advantage of
      this model is that it is a vascularized graft that can be visibly observed and
      easily biopsied, thus allowing for good correlation between gross and
      histological findings after transplantation. We plan to use this model further to
      study in detail the rejection patterns in an allograft and xenograft setting.

PMID- 9635796
TI  - Laser nerve repair by solid protein band technique. I: identification of optimal
      laser dose, power, and solder surface area.
AB  - Thirty-four tibial nerves in 17 adult male wistar rats were repaired by applying
      protein bands longitudinally across the nerve join. The bands were then
      irradiated with a fibre-coupled diode laser (lambda = 810 nm). The relations
      among the laser weld breaking force, the power, and the solder surface area were
      investigated, while maintaining a consistent ratio between the total mass of
      protein solder in a band and total laser energy delivered (the laser energy
      dose). When this laser energy dose was held constant, the average breaking force
      of the laser welds irradiated by 72 mW laser output power was weaker than that
      reached after 90 mW laser radiation. There is a linear relation between the
      solder breaking force and the solder surface area when band thickness, laser
      power, and laser dose are unvaried.

PMID- 9635795
TI  - Evans blue dye modifies the ultrastructure of normal and regenerating arterial
      endothelium in rats.
AB  - Evans blue dye (EBD) identifies areas of increased vascular permeability, which
      is usually indicative of endothelial damage. Most studies examine EBD-stained
      areas light-microscopically, but others analyze the cells with the electron
      microscope. Electron microscopic studies have assumed that EBD itself did not
      change the ultrastructure of endothelial cells and this hypothesis was tested in
      the following study. The left iliac arteries of 20 rats were injured with 1-mm
      vascular clamps for 5 minutes. At 7 and 14 days after clamping, 10 rats for each
      time were infused intravenously either with normal-saline or EBD, perfused 30
      minutes later with fixatives. Then the clamp-injured arteries, contralateral
      (unclamped) arteries, aortae, and the aortic bifurcations were removed for EM
      morphometry. In an additional (control) group of 10 rats, with no clamp injuries,
      5 were infused with EBD and 5 with normal-saline and all 10 rats were perfused 30
      minutes later, as above. EBD caused a significant simplification of the
      junctional morphology in both normal and regenerating endothelium. It also
      increased the area fractions of cytoplasmic vesicles in regenerating endothelium.
      These data demonstrate that EBD causes measurable ultrastructural changes in
      normal and regenerating endothelium. This effect should be taken into account
      when using EBD to assess various insults to blood vessels.

PMID- 9635797
TI  - Laser nerve repair by solid protein band technique. II: assessment of long-term
      nerve regeneration.
AB  - A total of 18 adult male Wistar rats had left tibial nerve repaired by either the
      laser-solder technique or a more conventional microsuture technique. The diode
      laser power was 90 mW and the radiation dose 16 J/mg. Three months
      postoperatively electrophysiology showed that the average compound muscle action
      potential (CMAP) of the laser repair group was not significantly different from
      the CMAP of the sutured nerves. Light microscopy confirmed regeneration of
      myelinated axons in both groups of animals. The laser-solder technique, when used
      with such parameters, proved to be a reliable method to achieve satisfactory
      peripheral nerve anastomosis and nerve regeneration.

PMID- 9635798
TI  - Cystic tumours of the pancreas.

PMID- 9635799
TI  - Skull radiographs and children with blunt head injury.

PMID- 9635800
TI  - Antibiotic prophylaxis in the initial management of severe acute pancreatitis.
AB  - BACKGROUND: The role of antibiotic prophylaxis in the initial management of
      patients with acute pancreatitis is an area of major controversy. Contrary to
      earlier clinical trials, recent experimental and clinical studies have accrued
      evidence that warrants reappraisal of current clinical practice. This article
      reviews these recent advances in knowledge. METHODS: All papers derived from a
      Medline search for the years 1990-1997 inclusive using the text words 'acute',
      'pancreatitis', 'antibiotic' and 'antibiotics' were studied. Additional papers
      were derived from reference lists within papers identified by the Medline search.
      Only experimental and clinical papers relevant to the issue of prophylactic
      antibiotic therapy in acute pancreatitis are included in the review. RESULTS AND
      CONCLUSION: Current experimental evidence favours the use of prophylactic
      antibiotics in severe acute pancreatitis. The results of contemporary randomized
      clinical trials restricted to patients with prognostically severe acute
      pancreatitis have demonstrated improvement in outcome associated with antibiotic
      treatment.

PMID- 9635801
TI  - Diagnosis and treatment of sphincter of Oddi dysfunction.
AB  - BACKGROUND Sphincter of Oddi dysfunction is a challenge from both the diagnostic
      and therapeutic point of view. There is much ongoing debate about the accuracy
      and usefulness of various diagnostic tests, as there is about the effectiveness
      of proposed therapeutic alternatives. METHODS: A comprehensive review of the past
      15 years' literature was undertaken, using the Medline database and cross
      referencing of major articles on the subject. RESULTS AND CONCLUSION: Endoscopic
      and surgical treatments result in similar outcomes, with considerable failure
      rates. The latter reflect the difficulties in accurate diagnosis and a lack of
      sound objective criteria for selecting patients for intervention. In addition, in
      some patients sphincter of Oddi dysfunction may be only part of a generalized
      motility disorder of the gastrointestinal tract.

PMID- 9635802
TI  - Recent advances in the surgical treatment of faecal incontinence.
AB  - BACKGROUND: Improved imaging and refined technology have led to a number of
      recent advances in the surgical treatment of faecal incontinence. METHODS:
      Original articles, identified using a computer database (Medline), and recently
      published abstracts of meetings were selected on the basis of greatest clinical
      relevance; these were reviewed. RESULTS: Ultrasonographic characterization has
      led to improved therapeutic strategies. Simple structural damage is readily
      identified and external sphincter repair results in a good outcome for a majority
      of patients. For more complex structural damage, or for the newly recognized
      primary internal sphincter degeneration, alternative treatment strategies are
      emerging. The electrically stimulated gracilis neosphincter and the artificial
      bowel sphincter offer good results. The latter may be a more simple operation.
      For structurally intact but weak sphincters, sacral nerve stimulation is a
      promising therapy. Other therapies, such as antegrade irrigation, may be helpful
      for patients with neurological disorders. CONCLUSION: Better imaging, refined
      classification and new operations are leading to improved surgical techniques for
      faecal incontinence.

PMID- 9635803
TI  - Simple laparoscopic gastropexy as the initial treatment of paraoesophageal hiatal
      hernia.
AB  - BACKGROUND: Paraoesophageal hiatal hernia is relatively rare compared with
      sliding hernia but it is associated with serious complications. Its clinical
      management presents a major challenge since many patients are elderly and unfit
      for a formal repair. This paper describes a laparoscopic method aimed at reducing
      the complications of open repair. METHODS: Thirteen patients treated for
      symptomatic paraoesophageal hernia were included in the study. Eleven patients
      successfully underwent a simple laparoscopic modification of the Boerema anterior
      gastropexy. Two patients required an open anterior gastropexy through a
      minilaparotomy because of incomplete reduction of the hernia. A five-puncture
      technique was used. The stomach and any other contents of the sac were reduced
      into the abdomen and the stomach was firmly fixed to the fascia of the anterior
      abdominal wall with GORE-TEX sutures tied extracorporeally. RESULTS: There was
      one postoperative death due to spontaneous intrathoracic perforation of the
      posterior aspect of the stomach in an elderly woman with severe cardiac disease.
      There was no postoperative morbidity. Eight of the ten patients who went home
      following laparoscopic gastropexy have remained asymptomatic on follow-up. In
      three patients, two in the laparoscopic group and one in the open group, symptoms
      recurred. CONCLUSION: While anterior gastropexy has a significant incidence of
      recurrent herniation, the clinical results of this simple procedure in a high
      risk population support its use as the initial surgical option.

PMID- 9635804
TI  - Pancreatic cancer resection in elderly patients.
AB  - BACKGROUND: Pancreatic cancer resection is considered a high-risk procedure in
      patients aged 70 years or older. METHODS: Some 398 patients with pancreatic
      adenocarcinoma, observed between 1990 and 1995, were reviewed. Operative outcome
      and survival of 33 patients aged 70 years or more were compared with findings in
      85 younger patients who underwent resection. RESULTS: Resectability was not
      significantly different between the elderly and younger patients; neither were
      mortality or overall morbidity. However, patients aged 70 years or more had more
      relaparotomies (P < 0.01) and more haemorrhagic complications (P < 0.001).
      Nutritional recovery after resection was satisfying even for elderly patients
      (body-weight gain and increase in serum albumin concentrations, P < 0.05).
      Univariate analysis showed a moderately poorer survival in the elderly (P =
      0.09). Multivariate analysis demonstrated that tumour diameter, grading and Union
      Internacional Contra la Cancrum stage were independent prognostic factors,
      whereas age was not. CONCLUSION: Patients aged 70 years or more can benefit from
      pancreatic cancer resection similarly to younger patients.

PMID- 9635805
TI  - Survival following pancreaticoduodenectomy with resection of the superior
      mesenteric-portal vein confluence for adenocarcinoma of the pancreatic head.
AB  - BACKGROUND: The survival of patients who underwent pancreaticoduodenectomy with
      or without en bloc resection of the superior mesenteric-portal vein (SMPV)
      confluence for adenocarcinoma of the pancreatic head was compared. METHODS: To be
      considered for surgery, patients were required to fulfil the following computed
      tomography criteria for resectability: (1) absence of extrapancreatic disease,
      (2) no evidence of tumour extension to the superior mesenteric artery (SMA) or
      coeliac axis, and (3) a patent SMPV confluence. Tumour adherence to the superior
      mesenteric vein (SMV) or SMPV confluence was assessed at operation and en bloc
      venous resection was performed when necessary to achieve complete tumour
      extirpation. RESULTS: Seventy-five consecutive patients underwent
      pancreaticoduodenectomy, 44 without venous resection and 31 with en bloc
      resection of the SMPV confluence. There were no perioperative deaths in either
      group; late (more than 6 months) occlusion of the reconstructed SMPV confluence
      contributed to the death of two patients. Median survival in the 31 patients who
      required venous resection at the time of pancreaticoduodenectomy was 22 months,
      and that for the 44 control patients was 20 months (P = 0.25). CONCLUSION:
      Patients with adenocarcinoma of the pancreatic head who require venous resection
      during pancreaticoduodenectomy for isolated tumour extension to the SMV or SMPV
      confluence (in the absence of tumour extension to the SMA or coeliac axis) have a
      duration of survival no different from that of patients who undergo standard
      pancreaticoduodenectomy. These data suggest that venous involvement is a function
      of tumour location rather than an indicator of aggressive tumour biology.

PMID- 9635806
TI  - Experimental study of a novel phospholipase A2 inhibitor in acute pancreatitis.
AB  - BACKGROUND: In acute pancreatitis, two different types of secretory phospholipase
      A2 (PLA2) have been found: pancreatic type I PLA2 and non-pancreatic type II
      PLA2. In this study a potent new PLA2 inhibitor effective against type II PLA2
      was used in an experimental model of acute pancreatitis. METHODS: In 70 rats the
      efficacy of the compound was analysed in two experimental models of acute
      pancreatitis: cerulein- and taurocholate-induced acute pancreatitis, imitating
      mild and severe disease respectively. Serum rat type I PLA2 protein concentration
      and type I and type II PLA2 catalytic activities were measured while giving the
      inhibitor therapeutically. In a prophylactic protocol the effect on histology was
      analysed. RESULTS: In the taurocholate model, type II PLA2 activity was found to
      be nine-fold higher than in the cerulein model (P < 0.002), whereas the activity
      of type I PLA2 was not increased. The inhibitor significantly decreased serum
      type II PLA2 activity in the taurocholate model of acute pancreatitis (P < 0.05)
      but type I PLA2 protein concentration and type I PLA2 activity were not affected.
      The inhibitor also reduced histological tissue damage, with significant
      differences at 3 and 12 h (P < 0.01). CONCLUSION: The PLA2 inhibitor
      significantly reduced type II PLA2 activity and was able to protect the pancreas
      against tissue damage. PLA2 inhibition offers the possibility of a treatment for
      acute pancreatitis.

PMID- 9635807
TI  - Laparoscopic cholangiography: a prospective study.
AB  - BACKGROUND: The place of cholangiography has been controversial in the
      conventional and now in the laparoscopic setting. The aim of this study was to
      evaluate laparoscopic cholangiography and compare use of a portable C-arm image
      intensifier with conventional radiography. METHODS: One hundred and ninety-seven
      consecutive patients undergoing laparoscopic cholecystectomy were randomized
      before operation to cholangiography by either C-arm image intensifier or
      conventional radiography. Data were collected on a pro forma completed
      immediately after the operation. RESULTS: Cholangiography was successful in 93.0
      per cent of patients. Cholangiography with an image intensifier was significantly
      faster. In 19 patients the ductal system was obscured by a cannula; in 17 of
      these cases a metal cannula was used. In 31.6 per cent of patients the clip on
      the cystic duct was within 1 cm or less of the common bile duct (CBD).
      CONCLUSION: Laparoscopic cholangiography is a safe procedure. Use of an image
      intensifier should be the preferred method of obtaining images. Metal cannulas
      are more likely to obscure the ductal system. The proximity of the clip on the
      cystic duct to the CBD highlights the potential for injury caused by
      electrocautery or erroneous clip application.

PMID- 9635808
TI  - Multidisciplinary approach to biliary complications of laparoscopic
      cholecystectomy.
AB  - BACKGROUND: Bile leaks and bile duct strictures are major complications of
      cholecystectomy which increased in incidence after the introduction of
      laparoscopic surgery. The management and outcome of these complications following
      the introduction of laparoscopic cholecystectomy was reviewed. METHODS: Eighteen
      patients of median age 45 (range 22-70) years were treated between January 1992
      and December 1995. Six patients had a common hepatic duct (CHD) stricture, four
      following a failed previous repair. Nine patients had bile leaks from bile duct
      transection (four), cystic stump (four) or segment V duct (one). Two patients had
      partial bile duct damage with primary sutured repair at time of cholecystectomy.
      One patient had recurrent haemobilia from a hepatic artery pseudoaneurysm.
      RESULTS: Cystic stump or segment V leaks were treated successfully by endoscopic
      stenting (median follow-up 42 months). Roux loop biliary reconstruction was
      carried out in nine patients: two CHD strictures, three of the four failed
      primary CHD repairs and four bile duct transections. All had normal liver
      function test results at median follow-up of 30 months. The two patients with
      partial duct injuries repaired at initial surgery required no further
      intervention. The right hepatic artery aneurysm was successfully embolized. There
      have been no deaths or major complications of endoscopic, radiological or
      surgical intervention. CONCLUSION: Endoscopic stenting successfully treats cystic
      stump and segment V duct leaks. Duct strictures, including failed initial repairs
      and transections, have a good outcome with Roux-en-Y loop reconstruction.

PMID- 9635809
TI  - Mortality following elective infrarenal aortic reconstruction: a Joint Vascular
      Research Group study.
AB  - BACKGROUND: This study aimed to define the cause of death in patients undergoing
      elective infrarenal aortic reconstruction. METHODS: Members of the Joint Vascular
      Research Group who had collected details prospectively of patients undergoing
      elective aortic reconstruction provided information on those who died. RESULTS:
      Details of 3786 patients were obtained. Some 171 patients died (133 following
      abdominal aortic aneurysm (AAA) and 38 after aortofemoral bifurcation graft
      (AFBG) for occlusive disease). The mortality rate following AAA repair was 4.8
      per cent, rising to 16 per cent if repair was combined with either renal or
      distal reconstruction (P < 0.001). Similar results were obtained with AFBG (3.4
      and 11 per cent respectively, P < 0.001). The first major complication
      encountered was cardiac (39.8 per cent), followed by bleeding (20.5 per cent),
      respiratory (13.5), and gut (5.3 per cent), or limb ischaemia (6.4 per cent).
      Bleeding was commoner following reconstruction for aneurysm compared with that
      for occlusive disease (P < 0.05). Eighty-six patients (50.3 per cent) died from
      the first major complication. Of the remainder, 45 (53 per cent) developed
      multisystem organ failure (MSOF). The most commonly involved systems were
      cardiac, respiratory and renal. CONCLUSION: Cardiac problems were the major cause
      of death following infrarenal aortic reconstruction. MSOF is the 'final common
      pathway' in about half of the patients who survive the initial complication.

PMID- 9635810
TI  - Survey of changes in the provision of vascular surgical services in the Oxford
      Region over 5 years.
AB  - AIM: This study aimed to examine changes in the provision of vascular services in
      the Oxford region over 5 years. METHODS: A questionnaire was sent to all general
      surgeons in the region asking of their involvement in vascular surgery. Data were
      obtained from the Department of Health concerning vascular procedures and
      inpatient codes for each district in the Oxford Region from 1990-1991 to 1994
      1995. Office of Population Censuses and Surveys (OPCS) data for abdominal aortic
      aneurysm repair and femoral artery reconstruction were validated against data
      collected prospectively for West Berkshire. RESULTS: Eighteen of 45 surgeons who
      replied to the questionnaire carried out elective and emergency arterial work.
      All were members of the Vascular Surgical Society of Great Britain and Ireland
      (VSS). All but one took part in the general surgical rota. Eight surgeons carried
      out emergency arterial surgery only; only two of these were members of the VSS.
      Of 19 surgeons undertaking no arterial surgery, 15 operated on primary and 11 on
      recurrent varicose veins. The number of arterial reconstructions rose from 20.8
      per 100000 population to 28 per 100000 throughout the study. The greatest
      increase occurred in districts where a new vascular consultant had been
      appointed. Similar results were obtained with endovascular procedures. The number
      of major amputations remained fairly constant at approximately 11 per 100000
      population. The number of inpatient episodes for arterial disease also rose, from
      35.7 to 47.6 per 100000. In validating OPCS codes against prospectively collected
      data, discrepancies for individual years were noted but the annual trend was
      reflected fairly accurately by the codes. CONCLUSION: There has been an increase
      in vascular activity in the region, but variations still exist between different
      districts.

PMID- 9635811
TI  - Role of magnetic resonance angiography for assessment of abdominal aortic
      aneurysm before endoluminal repair.
AB  - BACKGROUND: A detailed knowledge of the morphology of the aorta and iliac
      arteries is an important prerequisite for successful endoluminal abdominal aortic
      aneurysm (AAA) repair. The best method of preoperative evaluation remains to be
      determined. METHODS: A prospective study was undertaken between January 1994 and
      July 1995 to assess the ability of computed tomography (CT), magnetic resonance
      angiography (MRA), colour duplex imaging and intra-arterial digital subtraction
      angiography (IA-DSA) to visualize AAA morphology. RESULTS: Eighty-two consecutive
      patients (64 men, 18 women) with AAA were assessed with MRA, contrast-enhanced
      CT, colour duplex imaging and IA-DSA. Median age was 74 (range 59-87) years and
      median AAA diameter was 5.7 (range 3.5-9.7) cm. Five patients were unable to
      tolerate CT or MRA examination. Seventy-seven patients underwent both CT and MRA.
      Of these, 55 also had a colour duplex scan and 32 underwent arteriography. The
      scans were assessed by an independent blinded observer. MRA was significantly
      better (P < 0.01) at visualizing AAA morphology compared with CT and colour
      duplex imaging. There was no statistically significant difference between MRA and
      arteriography. CONCLUSION: MRA is useful in patient selection for endoluminal AAA
      repair, as it avoids use of iodinated contrast medium and ionizing radiation.

PMID- 9635812
TI  - A 21-year experience of abdominal aortic aneurysm operations in Edinburgh.
AB  - BACKGROUND: This study reviews the results of infrarenal abdominal aortic
      aneurysm (AAA) surgery over 21 years (1 January 1976 to 31 December 1996).
      METHODS: A prospectively gathered database was analysed. RESULTS: Infrarenal AAA
      repair was performed in 1515 patients: 492 (32.5 per cent) had elective repair of
      an asymptomatic AAA; 194 (12.8 per cent) had elective repair of a symptomatic
      AAA; 156 (10.3 per cent) had emergency repair of a symptomatic non-ruptured AAA;
      and 673 (44.4 per cent) had surgery for a ruptured AAA. The 30-day and/or same
      admission mortality rates were 6.1, 5.8, 14.1 and 37 per cent respectively.
      Operative mortality increased in all four groups over the study interval,
      although this only attained statistical significance in patients having elective
      repair of a symptomatic, non-ruptured AAA. There was a significant increase in
      the age of patients undergoing elective repair of an asymptomatic AAA, but not in
      the other three groups. There was also a significant increase in the proportion
      of straight 'tube' grafts inserted in all four groups. CONCLUSIONS: It remains
      the minority of patients who have elective operation before the onset of symptoms
      and/or rupture. Despite anaesthetic and surgical specialization, the results of
      AAA repair have not improved over the past two decades. Operative mortality may
      be increasing, possibly because of the increasing age and associated comorbidity
      of the patients presenting to this unit.

PMID- 9635814
TI  - Arteriovenous fistula using transposed basilic vein.
AB  - BACKGROUND: Patients who need long-term haemodialysis often require multiple
      operations to maintain their vascular access. The options for secondary or
      tertiary access procedures may become increasingly limited. Prosthetic conduits
      are commonly used in difficult cases but are associated with a high incidence of
      complications. METHODS: The brachial artery-transposed basilic vein arteriovenous
      fistula has been used in preference to a prosthetic graft on 31 occasions.
      RESULTS: There were no technical failures and 28 of these fistulas matured. No
      major infective complications occurred. CONCLUSION: This procedure should be
      considered before resorting to a prosthetic graft for vascular access.

PMID- 9635813
TI  - Population-based record linkage study of the incidence of abdominal aortic
      aneurysm in Western Australia in 1985-1994.
AB  - BACKGROUND: The incidence of abdominal aortic aneurysm (AAA) has increased
      steadily during the past 30 years. METHODS: Trends in the incidence and surgical
      intervention for AAA in Western Australia were reviewed for the interval 1985
      1994. A population-based health database was used to link morbidity and mortality
      records of all patients aged 55 years or more who died from rupture or were
      admitted and treated surgically for AAA. Three groups were separated for
      analysis: patients with a ruptured AAA, those admitted for elective repair and
      those admitted as an emergency with an acute (non-ruptured) aneurysm. RESULTS:
      There was a decline in the incidence of both emergency and elective procedures
      for AAA after 1992. While the mortality rate from ruptured AAA has also fallen
      since 1991, the overall case fatality rate for ruptured AAA has fallen by only
      1.3 per cent (from 80.7 to 79.3 per cent). CONCLUSION: The decline in mortality
      rate and emergency procedures may result from a fall in the incidence of ruptured
      AAA, due to an increasing rate of elective surgery before 1992. The decline in
      elective procedures from 1992 may be due to a fall in the prevalence of AAA owing
      to high rates of elective surgery, or to a fall in the incidence of the disease
      itself.

PMID- 9635815
TI  - Multimodality treatment in the control of deep musculoaponeurotic fibromatosis.
AB  - BACKGROUND: Deep musculoaponeurotic fibromatoses are rare soft tissue neoplasms
      with a propensity for local recurrence. METHODS: A retrospective analysis was
      carried out of the factors contributing to local disease control in 75 patients
      treated between 1963 and 1993. RESULTS: Multivariate analysis identified the type
      of surgical excision (P < 0.001) and involvement of pathological resection
      margins (P < 0.02) as significant factors contributing to local recurrence. After
      a median follow up of 47 months (range 24 months to 29 years) 31 (49 per cent) of
      the 63 patients who had an 'adequate' surgical resection developed local
      recurrence. The median time before development of local recurrence was 83.4
      (range 8-129) months in patients with clear pathological resection margins. This
      was significantly shortened to 13.1 (range 2-35) months in those with positive
      margins (P < 0.001). CONCLUSION: Adequate surgical extirpation is the most
      important determinant in local disease control. Treatment of local recurrence
      ranged from observation during periods of disease stabilization to multimodality
      treatment for aggressive disease.

PMID- 9635816
TI  - Anovestibular fistula to Bartholin's gland.
AB  - BACKGROUND: Acquired fistulation from the anal canal to Bartholin's gland has not
      been reported before. This fistula has been identified in 11 women treated
      between 1991 and 1995. METHODS: All discharge diagnoses during this period were
      searched. The clinical records of patients managed for this diagnosis were
      reviewed. RESULTS: Eleven women aged 24-49 years were identified. Seven of 11
      fistulas arose in association with inflammatory bowel disease (five Crohn's
      disease, two ulcerative colitis). Patients typically presented with the vulval
      passage of flatus and faeces or acute sepsis of Bartholin's gland. Time to
      diagnosis of the fistula ranged from 1 to 15 (median 8) months after the onset of
      symptoms. Anatomically, all fistulas were high trans-sphincteric or
      suprasphincteric. All eight fistulas for which repair was attempted (five in the
      presence of inflammatory bowel disease) remain healed at short-term follow-up.
      Proctocolectomy was undertaken in two patients with severe Crohn's colitis.
      CONCLUSION: Ano-Bartholin's fistulas, although rare in general surgical practice,
      present with troublesome symptoms and may be repaired successfully.
      Gynaecologists and surgeons should be aware of this clinical entity to avoid
      unnecessary delays in treatment.

PMID- 9635817
TI  - Outcome following laparoscopic resection for colorectal cancer.
AB  - BACKGROUND: A prospective comparison of laparoscopic or laparoscopically assisted
      colorectal resection versus open resection has been undertaken to evaluate early
      benefits and cost implications. METHODS: Consecutive patients with colorectal
      cancer underwent either elective laparoscopic (n = 25) or open (n = 29)
      resection. RESULTS: Mean hospital stay was significantly shorter in the
      laparoscopic group: 10.7 versus 17.8 days. Mean morphine requirements were less
      in patients who had laparoscopic resection and their recovery, as measured by the
      dynamometer hand grip and the SF-36 symptom score, was more rapid. Adequate
      tumour clearance was achieved in the laparoscopic group. In both groups, the
      number of lymph nodes harvested was similar. Port-site or wound recurrence has
      not been observed at a median follow-up of 28 months. CONCLUSION: When
      laparoscopic colorectal resection is possible, there are significant early
      benefits for patients.

PMID- 9635818
TI  - Surgical treatment of severe duodenal polyposis in familial adenomatous
      polyposis.
AB  - BACKGROUND: Patients with familial adenomatous polyposis (FAP) are at risk for
      adenomas and cancers in the duodenum but the ideal management of duodenal
      polyposis remains uncertain. METHODS: The outcome of surgical resection was
      analysed in 18 patients with FAP who had severe duodenal polyposis. RESULTS:
      Duodenotomy and clearance of duodenal adenomas was performed seven times in six
      patients. There were two duodenal leaks and, after a mean follow-up of 53 (range
      36-72) months, duodenal adenomas recurred in all patients and five had severe
      polyposis. Pancreatoduodenectomy was performed in seven patients with severe
      duodenal polyposis. Histology of the specimens revealed two unsuspected duodenal
      carcinomas at an early stage. After a mean follow-up of 42 months all patients
      were alive and well, and there was no case of jejunal polyposis.
      Pancreatoduodenectomy was attempted in five patients with duodenal cancer and
      only one survived more than 4 years. CONCLUSION: Surgical excision of duodenal
      adenomas should be discussed before carcinoma occurs. Surgical polypectomy fails
      to guarantee a polyp-free duodenum and carries a risk of postoperative
      complications whereas pancreatoduodenectomy eliminates the risk of duodenal
      cancer with an acceptable morbidity rate. Pancreatoduodenectomy could be offered
      to some patients with large or multiple villous duodenal adenomas repeatedly
      showing severe dysplasia.

PMID- 9635819
TI  - Assessment of a scoring system for breast imaging.
AB  - BACKGROUND: Triple assessment is the standard method of assessing symptomatic
      breast lumps. There is an accepted format for reporting cytology but not for the
      reporting of mammograms or breast ultrasonographic images. This study describes a
      scoring system for reporting breast imaging methods. METHODS: Patients with
      symptomatic breast lumps seen during 1 year were included. All patients underwent
      triple assessment. Imaging studies were reported using a grading system from 1 to
      5. The results of triple assessment were compared with the final histology.
      RESULTS: Some 127 women had both mammography and ultrasonographic imaging; the
      final grade was identical in 60 per cent. The positive predictive value of
      imaging reported as grade 5 or 4 combined with cytology of C5 or C4 was 100 per
      cent. All lesions with C3 cytology and benign imaging were benign on histological
      examination whereas if a C3 grade was combined with imaging grade 5 or 4, all the
      lesions were malignant. CONCLUSION: Combining the imaging grade with the results
      of aspiration cytology and clinical examination often predicts the final
      histology in patients with breast disease.

PMID- 9635821
TI  - Experimental study of acid burden and acute oesophagitis.
AB  - BACKGROUND: The relationship of the pH of oesophageal refluxate and its pepsin
      content to injury of oesophageal mucosa remains unclear. A study was made of the
      earliest morphological alterations in the oesophageal mucosa secondary to varying
      concentrations of hydrochloric acid with or without pepsin. METHODS: Adult cats
      had varying concentrations of acid with and without 1 per cent porcine pepsin
      infused into the oesophagus through a paediatric feeding tube placed 5 cm above
      the oesophagogastric junction at a rate of 1 ml/min for 30 min. At autopsy 24 h
      later, the oesophagus was removed intact and scored by an expanded modification
      of a previously published histopathological scoring system. This included
      estimates of the intensity and distribution of four morphological features: basal
      cell hyperplasia (BCH), intraepithelial leucocytes (IELs), subepithelial
      leucocytes and ulcers. Each of these four categories was scored from 0 to 4, with
      a maximum injury score of 16. RESULTS: Mean(s.e.m.) scores were as follows: pH 1,
      15.0(1.0); pH 1 with pepsin, 13.3(1.4); pH 2, 15.3(0.7); pH 2 with pepsin,
      11.7(1.1); pH 3, 1.8(1.6); pH 3 with pepsin, 3.7(1.9); pH 4 with or without
      pepsin, 0.6(0.2). Differences between pH 3 and 4 versus pH 1 and 2 were
      significant (P < 0.05). CONCLUSION: Injury to the oesophagus is more dependent on
      the pH of refluxate than on the presence of pepsin. Peptic injury appears to
      occur at a critical threshold of acid burden (pH < 3) as opposed to a graded
      level of injury based on a pH scale.

PMID- 9635820
TI  - Effect of graft reperfusion on intracellular calcium levels in mononuclear
      leucocytes during human orthotopic liver transplantation.
AB  - BACKGROUND: Orthotopic liver transplantation (OLT) is accompanied by local and
      systemic manifestations of the ischaemia-reperfusion syndrome. Local effects are
      mediated in part through changes in intracellular calcium levels in Kupffer
      cells. Arachidonic acid metabolites mediate increases in intracellular calcium
      concentration and thus potentiate the effect of free radicals. This study was
      carried out to characterize white blood cell (WBC) calcium changes as a mediator
      for white cell activation in human OLT. METHODS: Twenty consecutive patients had
      OLT using standard surgery and anaesthesia techniques. Blood samples were drawn
      for estimation of WBC cytosolic calcium content at induction of anaesthesia, 5
      min before graft reperfusion and 15 min after reperfusion. The rate of rise in
      intracellular calcium concentration after the addition of a calcium chloride 1
      mmol L(-1) solution to the extracellular milieu was used as an estimate of
      membrane calcium permeability. RESULTS: Both extracellular (P = 0.0002) and
      intracellular (P = 0.0008) calcium concentrations rose with time. However, at no
      time was there a correlation between extracellular and intracellular calcium
      levels or rate of calcium influx (r2 = 0.002, P = 0.78). There was a significant
      increase in intracellular calcium concentration (P = 0.0008) and in the rate of
      rise of intracellular calcium levels (P = 0.0009) after reperfusion. CONCLUSION:
      There was a significant increase in circulating monocyte membrane permeability
      for calcium and cytosolic calcium concentration following reperfusion in human
      OLT. This was independent of extracellular calcium concentration. These results
      are consistent with WBC activation by reperfusion and could be implicated in the
      systemic reperfusion syndrome seen in OLT in humans.

PMID- 9635822
TI  - Association between restriction fragment length polymorphism of the L-myc gene
      and susceptibility to gastric cancer.
AB  - BACKGROUND: L-myc polymorphism has been documented to be a representative genetic
      trait which is related an individual's susceptibility to several cancers.
      However, there have been no reports concerning any significant association
      between susceptibility to gastric cancer and L-myc polymorphism. METHODS: The
      distribution of L-myc polymorphism in 61 patients with gastric cancer was
      determined by polymerase chain reaction-based restriction fragment length
      polymorphism and compared with that of 107 healthy control subjects. RESULTS:
      There was a significant difference in the distribution of both genotypes (P =
      0.024) and allele frequencies (P = 0.026) between the two groups. The relative
      risk of gastric cancer for genotypes with the shorter (S) allele was 3.09
      compared with the longer (L) allele homozygote. No significant correlation with
      clinicopathological features of the cancers except for prognosis was found. The
      patients with SS genotypes had a worse prognosis than those with LL or LS
      genotypes (P = 0.029). CONCLUSION: L-myc polymorphism may be significant in an
      individual's susceptibility to gastric cancer in Japan, and may be a useful
      marker for identifying patients at high risk of developing gastric cancer.

PMID- 9635823
TI  - Enteral nutrition is superior to parenteral nutrition in severe acute
      pancreatitis: results of a randomized prospective trial.

PMID- 9635824
TI  - Randomized controlled trial of open and closed haemorrhoidectomy.

PMID- 9635825
TI  - Comparison of endoanal magnetic resonance imaging with surgical findings in
      perirectal sepsis.

PMID- 9635826
TI  - Health economics and quality of life in cancer trials: report based on a UKCCCR
      workshop. United Kingdom Coordinating Committee on Cancer Research.

PMID- 9635827
TI  - Alteration of oestradiol metabolism in myc oncogene-transfected mouse mammary
      epithelial cells.
AB  - Targeted overexpression of the c-myc oncogene induces neoplastic transformation
      in immortalized, non-tumorigenic mouse mammary epithelial cells (MMEC).
      Experiments in the present study were conducted to examine whether cellular
      transformation induced by c-myc oncogene is associated with altered metabolism of
      17beta-oestradiol (E2). The parental, MMEC and the stable c-myc transfectant
      (MMEC/myc3) cell lines were compared for major oestrogen metabolic pathways,
      namely E2 and E1 interconversion, and C2- and C16alpha-hydroxylation by both high
      pressure liquid chromatography (HPLC) analysis and the 3H release assay using
      specifically labelled [C2-3H]E2 or [C16alpha-3H]E2. The reductive conversion of
      E1 to E2 was about 14-fold and 12-fold higher than the oxidative conversion of E2
      to E1 in MMEC and MMEC/myc3 cells respectively. However, in MMEC/myc3 cells, both
      reductive and oxidative reactions were decreased by about 32% and 12% relative to
      those seen in the parental MMEC cells (P = 0.0028). The extent of C16alpha
      hydroxylation was increased by 164.3% (P < 0.001), with a concomitant 48.4%
      decrease (P < 0.001) in C2-hydroxylation in MMEC/myc3 cells; this resulted in a
      fourfold increase in the C16alpha/C2 hydroxylation ratio in this cell line. Thus,
      a persistent c-myc expression, leading to aberrant hyperproliferation in vitro
      and tumorigenesis in vivo, is associated with an altered oestrogen metabolism.
      However, it remains unclear whether this represents a result of oncogene
      expression/activation or is rather a consequence of phenotypic transformation of
      the cells.

PMID- 9635828
TI  - Temperature sensitivity of human wild-type and mutant p53 proteins expressed in
      vivo.
AB  - p53 is activated in response to DNA damage and functions in the maintenance of
      genetic integrity. Loss of p53 function because of mutation of the p53 gene is
      associated with over half all human cancers. Certain human p53 mutants are
      conformationally flexible in vitro and are temperature sensitive, with partial or
      complete recovery of wild-type (wt) properties at 32 degrees C. We have now
      tested the functional capacities of selected p53 mutants in vivo, by transfection
      into established human cell lines. Unexpectedly, we found that wt p53 can be
      temperature sensitive for transactivation of a co-transfected target gene in
      vivo. Flexible mutants retained varying degrees of functional capacity in
      transfected cells, and the recipient cell line appeared to be a significant
      determinant of both wt and mutant p53 function; importantly, two p53 null cell
      lines commonly used to study p53 function (Saos-2 and Hep3B) differed markedly in
      this latter respect. We also show that the p53 mutant V272M, which exhibits
      sequence-specific DNA binding in vitro, is nonetheless defective for
      transactivation and is unable to induce apoptosis in vivo. The valine 272 residue
      may thus be crucial for properties (other than sequence-specific DNA binding)
      that are important for p53 function(s) in vivo.

PMID- 9635829
TI  - Expression of p53, Bcl-2 and Bax in cisplatin-induced apoptosis in testicular
      germ cell tumour cell lines.
AB  - We examined the sensitivity for cisplatin-induced apoptosis in a panel of four
      testicular germ cell tumour (TGCT) cell lines and monitored the cellular
      expression of the apoptosis-related proteins p53, Bcl-2 and Bax. Three of four
      TGCT cell lines (NT2, NCCIT and S2) were hypersensitive for cisplatin-induced
      apoptosis, while the TGCT cell line 2102 EP appeared to be resistant for
      cisplatin-induced apoptosis, even at relatively high drug concentrations (12.5
      microM). For all four cell lines, the induction of apoptosis by cisplatin
      correlated with drug sensitivity in the MTT assay. The differences in
      chemosensitivity and induction of apoptosis could not be attributed to
      differences in cellular platinum accumulation, DNA platination or platinum-DNA
      adduct removal. We next analysed the relationship between p53 status and
      cisplatin-induced up-regulation of p53, and the susceptibility to cisplatin
      induced apoptosis. Wild-type p53 containing NT2 and 2102 EP cells showed p53 up
      regulation upon drug treatment, and NCCIT (mutant p53) and S2 (no p53 protein)
      cells did not. Consistently, the increase in wild-type p53 protein in NT2 and
      2102 EP cells led to an increase in mRNA level of the p53 downstream gene
      p21/WAF/CIP, whereas mutant p53-containing NCCIT cells and p53-non-expressing S2
      cells could not transactivate this p53-responsive gene. As NT2, NCCIT and S2 were
      readily triggered into apoptosis, while 2102 EP cells failed to undergo cisplatin
      induced apoptosis, our data suggest that the presence of wild-type and/or
      transactivation-competent p53 might not be an absolute prerequisite for efficient
      induction of apoptosis in TGCT cell lines. Also endogenous levels of Bcl-2 and
      Bax expression did not correlate with cisplatin-induced apoptosis. In addition,
      the endogenous Bcl-2 and Bax expression was not affected by cisplatin treatment.
      The present study suggests that, at least in our panel of TGCT cell lines,
      hypersensitivity for cisplatin-induced apoptosis might not be necessarily
      correlated with the presence of wild-type p53 and is probably not associated with
      Bcl-2 and Bax expression.

PMID- 9635830
TI  - p53 mutations in non-small-cell lung cancers occurring in individuals without a
      past history of active smoking.
AB  - Accumulating evidence suggests that the p53 gene is a good target for molecular
      epidemiological studies. We previously reported an association between the
      presence of p53 mutations and lifetime cigarette consumption. Although over 675
      p53 mutations have been reported in lung cancers in the literature thus far, very
      little is known about the nature of such changes in lung cancers in the absence
      of a smoking background. In the present study, we therefore analysed 69 non-small
      cell lung cancer specimens from individuals without any history of active smoking
      and identified p53 mutations in 26% of the cases. Statistical analysis of the
      present cohort of non-smokers also showed absence of significant relationship
      between p53 mutations and age, sex, histological type or disease stage.
      Comparison of mutational spectra between the present results in non-smokers and
      previously reported mutations in smokers clearly demonstrated G:C to T:A
      transversions to be significantly less frequent in non-smokers than in smokers
      (OR 5.35, 95% CI 1.77-16.12). Interestingly, G:C to C:G and G:C to A:T mutations
      were also observed in tumours of non-smokers at similar frequencies to G:C to T:A
      mutations, suggesting that these mutations can occur relatively frequently in the
      absence of active smoking. This study is, to our knowledge, the largest so far
      analysing a well-defined cohort of non-smokers in a single laboratory.

PMID- 9635831
TI  - Analysis of p53, p16MTS, p21WAF1 and H-ras in archived bladder tumours from
      workers exposed to aromatic amines.
AB  - Exposure to aromatic amines is considered a major risk factor for the development
      of bladder cancer. In this study, we have analysed the pattern of point mutations
      in several tumour genes in 21 cases of bladder cancer arising among western
      European workers exposed to aromatic amines in an attempt to determine whether
      this exposure may be associated with a unique spectrum of mutations. Of the four
      genes analysed (p53, p16MTS1, p21WAF1 and H-ras), only p53 showed a high
      frequency of mutations (in 8 out of 21 cases, 38%). Two mutations were found in
      p16, one in H-ras and none in p21 exon 3. All mutations were at G:C base pairs,
      mostly at non-CpG residues. This spectrum of mutations, which is highly
      suggestive of an involvement of exogenous carcinogens, is however identical to
      the spectrum of p53 mutations detected in bladder cancers of the general
      population. In exposed workers, p53 mutations were associated with tumour grade
      and with high occupational and tobacco exposure. Taken together, our data suggest
      that the same carcinogens may be responsible for the development of bladder
      cancers in workers exposed to aromatic amines and in the general population.

PMID- 9635832
TI  - Cytotoxicity of weak electrolytes after the adaptation of cells to low pH: role
      of the transmembrane pH gradient.
AB  - Theory suggests that the transmembrane pH gradient may be a major determinant of
      the distribution of lipophilic weak electrolytes across the cell membrane. The
      present study evaluates the extent to which this factor contributes to pH
      dependent changes in the cytotoxicity of two such chemotherapeutic drugs:
      chlorambucil and mitoxantrone. Experiments were performed with two cell types of
      the same origin but exhibiting different pH gradients at the same extracellular
      pH (pHe): CHO cells cultured under normal physiological conditions (pH 7.4) and
      acid-adapted cells obtained by culturing under low pH conditions (6.8). Over the
      pHe range examined (6.0-7.6), the difference between intracellular pH (pHi) and
      pHe increased with decreasing pHe. Acid-adapted cells were more resistant to
      acute changes in pHi than normal cells, resulting in substantially larger
      gradients in these cells. Drug cell survival curves were performed at pHe values
      of 6.4, 6.8 and 7.4. The cytotoxicity of chlorambucil, a weak acid, increased
      with decreasing pHe, and low pH-adapted cells were more sensitive than normal
      cells at the same pHe. In contrast, for the weak base, mitoxantrone, cytotoxicity
      increased with pHe and was more pronounced in normal cells. As predicted by the
      theory, the cytotoxicity of both drugs changed exponentially as a function of the
      pH gradient, regardless of cell type. For mitoxantrone, the rate of such change
      in cytotoxicity with the gradient was approximately two times greater than for
      chlorambucil. This difference is probably due to the presence of two equally
      ionizable crucial groups on mitoxantrone vs one group on chlorambucil. It is
      concluded that the cellular pH gradient plays a major role in the pH-dependent
      modulation of cytotoxicity in these weak electrolytes. The data obtained also
      suggest that a pronounced differential cytotoxicity may be expected in vivo in
      tumour vs normal tissue. In comparison with normal cells at a pHe of 7.4 (a model
      of cells in normal tissues), acid-adapted cells at a pHe of 6.8 (a model of cells
      distal from supplying blood vessels in tumours) were more sensitive to
      chlorambucil, with a dose-modifying factor of approximately 6, and were more
      resistant to mitoxantrone by a factor of 14.

PMID- 9635833
TI  - Increased plasminogen binding is associated with metastatic breast cancer cells:
      differential expression of plasminogen binding proteins.
AB  - Overexpression of urokinase-type plasminogen activator and its receptor
      correlates with metastatic capacity in breast cancer. In this study we show that
      the urokinase/urokinase receptor-overexpressing, metastatic human breast cancer
      cell line MDA-MB-231 (1) bound significantly more cell-surface plasminogen in a
      lysine-dependent manner and (2) was capable of generating large amounts of
      plasmin compared with the non-metastatic cell lines MCF-7 and T-47D. In addition,
      distinct plasminogen binding proteins were detected in the plasma membranes of
      the cell lines, suggesting heterogeneity of binding proteins. Plasminogen binding
      was analysed using a combination of dual-colour fluorescence flow cytometry and
      ligand histochemistry (for comparative and cellular localization of ligand
      binding), and fluorimetry (for Scatchard analysis). Apart from revealing the
      greater plasminogen binding capacity of MDA-MB-231 cells, flow cytometry and
      histochemistry also revealed that, in all three cell lines, non-viable or
      permeabilized cells bound significantly more plasminogen in a lysine-dependent
      manner than viable or non-permeabilized cells. Viable MDA-MB-231 cells bound
      plasminogen with moderate affinity and high capacity (Kd = 1.8 microM, receptor
      sites per cell 5.0 x 10(7). Our results indicate that differences in cell surface
      specific plasminogen binding capacity between cell lines may not be detectable
      with binding techniques that cannot distinguish between viable and non-viable
      cells.

PMID- 9635834
TI  - In vitro testing of calcium channel blockers and cytotoxic chemotherapy in B-cell
      low-grade non-Hodgkin's lymphoma.
AB  - The flux of calcium forms an important intracellular messenger system. The bcl-2
      oncoprotein is thought to make cells resistant to a variety of insults, including
      cytotoxic drugs, by the suppression of apoptosis, which appears to involve the
      repartitioning of intracellular calcium. Three drugs that affect calcium pathways
      and may influence this repartitioning, i.e. dantrolene, azumolene (a water
      soluble dantrolene analogue) and nimodipine, were studied in cell culture, using
      both a transformed follicle centre lymphoma cell line and primary culture of
      lymphoma cells in vitro in a manner that resulted in a growth pattern closely
      resembling that of the malignancy in vivo. Dantrolene and azumolene were potent
      inducers of cell death in both systems reducing the viable cell count by 70-90%
      in comparison with normal controls. Nimodipine, in comparison, appeared to have
      no significant effect. These results obtained in an in vitro setting suggest that
      further evaluation of dantrolene and azumolene for the treatment of low-grade non
      Hodgkin's lymphoma is warranted.

PMID- 9635835
TI  - Allelic imbalance and instability of microsatellite loci on chromosome 1p in
      human non-small-cell lung cancer.
AB  - The mapping of allelic loss on the short arm of chromosome 1 has been performed
      in non-small-cell lung cancer. We used a set of 11 microsatellite loci spanning
      1p to examine the frequency of allelic imbalance in a panel of 58 tumours. Fifty
      one of 58 (87.9%) cases have shown somatic allelic loss at one or more loci
      tested. The two shortest regions of the overlap (SRO) of the deletions have been
      identified: SRO 1 at 1p13.1 and SRO 2 at 1p32-pter. Allelic losses at these
      regions have been compared among adenocarcinoma and squamous cell carcinoma and
      no difference has been found. In contrast to SRO 1, deletions at SRO 2
      significantly correlated with advanced stage of the disease as well as post
      operative metastasizing and relapse. These data may suggest that SRO 1 and SRO 2
      can harbour tumour-supressor genes (TSGs) involved in different stages of NSCLC
      development. SRO 2 is still quite large and its refined mapping should help
      attempts to clone and identify the putative TSG(s). Microsatellite instability
      (replication errors) affecting only 6 (10.3%) of 58 tumour samples is an
      infrequent genetic alteration at the loci tested.

PMID- 9635836
TI  - Gamma-linolenic acid (GLA) is cytotoxic to 36B10 malignant rat astrocytoma cells
      but not to 'normal' rat astrocytes.
AB  - This study compares the effect of gamma-linolenic acid (GLA) and its precursor
      linoleic acid (LA) on survival of 36B10 malignant rat astrocytoma cells and
      'normal' rat astrocytes. GLA was cytotoxic to 36B10 cells but not to astrocytes.
      By contrast, LA supplementation did not affect the survival of either cell types.
      There were minor differences in the uptake, distribution and use of radiolabelled
      GLA and LA by the 36B10 cells and astrocytes. GLA and LA supplementation
      increased the total polyunsaturated fatty acid (PUFA) content of the cells
      indicating increased oxidative potential. However, elevated levels of 8
      isoprostane, an indicator of increased oxidative stress, were only observed in
      the GLA supplemented 36B10 cells. Addition of the antioxidant trolox to GLA
      enriched 36B10 cells blocked the cytotoxic effect. Further, GLA enhanced the
      radiation sensitivity of the astrocytoma cells but not the astrocytes; trolox
      blocked the GLA-mediated increase in astrocytoma cell radiosensitivity. LA did
      not affect the radiation response of either cell type. While cyclo-oxygenase
      inhibitors did not affect GLA cytotoxicity, they blocked the enhanced radiation
      response of GLA-supplemented cells. The lipoxygenase inhibitor NDGA did not
      affect the toxicity produced by GLA. Thus, GLA is toxic to the neoplastic
      astrocytoma cells but not to normal astrocytes.

PMID- 9635837
TI  - The influence of hypoxia and pH on aminolaevulinic acid-induced photodynamic
      therapy in bladder cancer cells in vitro.
AB  - Photodynamic therapy (PDT) is a cancer treatment based on the interaction of
      light and a photosensitizing chemical. The photosensitizer protoporphyrin IX
      (PpIX) is generated via the haem biosynthetic pathway after administration of
      aminolaevulinic acid (ALA). The cellular microenvironment of tumours is hypoxic
      and acidotic relative to normal tissue, which may influence PpIX generation and
      compromise PDT efficacy. This study used bladder cancer cells, incubated with ALA
      at various oxygen tensions and H+ ion concentrations, and assessed the effects on
      PpIX generation and PDT sensitivity. PpIX production was reduced at 0%, 2.5% (19
      mmHg) and 5% (38 mmHg) oxygen compared with that at 21% (160 mmHg) oxygen (0.15,
      0.28 and 0.398 ng microg(-1) protein compared with 0.68 ng microg(-1)
      respectively; P < 0.05). The response to PDT was abolished by hypoxia, as a
      result of both reduced PpIX synthesis and reduced PDT toxicity. PpIX production
      was greater at pH 7.0 and 6.5 (0.75 and 0.66 ng microg(-1)) compared with that at
      pH 7.4 and 5.5 (0.41 and 0.55 ng microg(-1) respectively). PDT cytotoxicity was
      enhanced at lower pH values. These results suggest that ALA-induced PDT may be
      inhibited by hypoxia due to reduced intrinsic PpIX synthesis. Acidosis may
      slightly enhance the efficacy of ALA-induced PDT.

PMID- 9635838
TI  - Absence of stimulation of poly(ADP-ribose) polymerase activity in patients
      predisposed to colon cancer.
AB  - Poly(ADP-ribose)polymerase (PARP) has been implicated in DNA repair mechanisms
      and the associated activity shown to markedly increase after DNA damage in
      carcinogen-treated cells. A defective DNA repair has been associated to the
      aetiology of human cancers. In order to assess the potential role of this enzyme
      in cellular response to DNA damage by gamma-radiation, we studied the activity of
      PARP in patients with familial adenomatous polyposis (FAP). We compared poly(ADP
      ribose)polymerase activity by the rate of incorporation of radioactivity from
      [3H]adenine-NAD+ into acid-insoluble material in permeabilized leucocytes from
      FAP patients and healthy volunteers. Concomitantly, the intracellular levels of
      NAD+--the substrate for the PARP--and the reduced counterpart NADH were
      determined using an enzymatic cycling assay 30 min after [60Co] gamma-ray cells
      irradiation. Our results demonstrate that a marked stimulation of PARP activity
      is produced upon radiation of the cells from healthy subjects but not in the FAP
      leucocytes, which concomitantly show a marked decrease in total NAD-/NADH
      content. Our observations point to a role of PARP in the repair of the gamma
      radiation-induced DNA lesions through a mechanism that is impaired in the cells
      from FAP patients genetically predisposed to colon cancer. The differences
      observed in PARP activation by gamma-radiation in patients and healthy
      individuals could reflect the importance of PARP activity dependent on treatment
      with gamma-rays. The absence of this response in FAP patients would seem to
      suggest a possible defect in the role of PARP in radiation-induced DNA repair in
      this cancer-prone disease.

PMID- 9635839
TI  - Telomerase activity in 144 brain tumours.
AB  - Unlimited proliferation in immortalized cells is believed to be highly dependent
      on the activity of telomerase, a ribonucleoprotein that synthesizes telomeric
      repeats onto chromosome ends. Using a polymerase chain reaction-based telomeric
      repeat amplification protocol (TRAP) assay, we analysed telomerase activity in 99
      benign and 45 malignant brain tumours. The TRAP assay results were quantitated by
      normalizing the telomerase activity of each specimen to that of human glioma cell
      line T98G to obtain the relative telomerase activity. Telomerase activity was
      also assessed visually from the autoradiograms as being positive or negative. One
      hundred and sixteen tumours with negative telomerase activity had null relative
      telomerase activity, whereas 28 tumours with positive telomerase activity had
      relative telomerase activities of 12-84.3% (mean 0% vs 36.1 +/- 19.3%, P <
      0.0001). Thus, quantification of telomerase activity confirmed the results of the
      visual evaluation of telomerase activity on autoradiograms. Based on the
      assessment, malignant brain tumours had a higher positive rate of telomerase
      activity than benign tumours (57.8% vs 2.0%, P < 0.001). These data indicate that
      positive telomerase activity is strongly associated with malignant brain tumours
      and is rather rare in benign tumours, such as neurinomas or meningiomas.

PMID- 9635840
TI  - Semi-quantitation of urokinase plasminogen activator and its receptor in breast
      carcinomas by immunocytochemistry.
AB  - Urokinase plasminogen activator (uPA) is a serine protease involved in cancer
      invasion and metastasis. uPA acts in vivo by binding to a membrane receptor known
      as uPAR. In this study, uPA and uPAR levels were semiquantitated by
      immunocytochemistry in 36 primary breast carcinomas. Using monoclonal antibody HD
      UK 1, uPA was detected both in stromal and in malignant cells. However, the
      predominant location was in the stromal cells. Using double-staining, cells
      containing uPA were also found to coexpress either cytokeratin (an epithelial
      cell marker) or more frequently KP1 (a macrophage/monocyte cell marker). With
      monoclonal antibody HD-uPAR 13.1, uPAR was localized principally to spindle- or
      macrophage-like stromal cells, especially when these cells surrounded invasive
      breast cancer. In contrast, uPAR was only rarely detected in cancer cells and was
      not detected in normal epithelia surrounding tumour or in areas of adenosis. uPA
      levels in both stromal and epithelial cells were significantly correlated with
      those for uPAR. We conclude that both uPA and its receptor are mostly present in
      stromal cells in invasive breast carcinomas. These results suggest that stromal
      cells collaborate with malignant cells to mediate metastasis.

PMID- 9635841
TI  - Mutation analysis of the c-mos proto-oncogene in human ovarian teratomas.
AB  - Female transgenic mice lacking a functional c-mos proto-oncogene develop ovarian
      teratomas, indicating that c-mos may behave as a tumour-suppressor gene for this
      type of tumour. We have analysed the entire coding region of the c-MOS gene in a
      series of human ovarian teratomas to determine whether there are any cancer
      causing alterations. DNA from twenty teratomas was analysed by single-strand
      conformational analysis (SSCA) and heteroduplex analysis (HA) to screen for
      somatic and germline mutations. In nine of these tumours the entire gene was also
      sequenced. A previously reported polymorphism and a single new sequence variant
      were identified, neither of which we would predict to be disease-causing
      alterations. These results suggest that mutations in the coding region of the c
      MOS gene do not play a significant role in the genesis of human ovarian
      teratomas.

PMID- 9635842
TI  - Reduced cellular accumulation of topotecan: a novel mechanism of resistance in a
      human ovarian cancer cell line.
AB  - In order to unravel possible mechanisms of clinical resistance to topoisomerase I
      inhibitors, we developed a topotecan-resistant human IGROV-1 ovarian cancer cell
      line, denoted IGROV(T100r), by stepwise increased exposure to topotecan (TPT).
      The IGROV(T100r) cell line was 29-fold resistant to TPT and strongly cross
      resistant to SN-38 (51-fold). However, the IGROV(T100r) showed only threefold
      resistance to camptothecin (CPT). Remarkably, this cell line was 32-fold
      resistant to mitoxantrone, whereas no significant cross-resistance against other
      cytostatic drugs was observed. No differences in topoisomerase I protein levels
      and catalytic activity as well as topoisomerase I cleavable complex stabilization
      by CPT in the IGROV-1 and IGROV(T100r) cell lines were observed, indicating that
      resistance in the IGROV(T100r) cell line was not related to topoisomerase I
      related changes. However, resistance in the resistant IGROV(T100r) cell line to
      TPT and SN-38 was accompanied by decreased accumulation of the drugs to
      approximately 15% and 36% of that obtained in IGROV-1 respectively. No reduced
      accumulation was observed for CPT. Notably, accumulation of TPT in the IGROV-1
      cell line decreased under energy-deprived conditions, whereas the accumulation in
      the IGROV(T100r) cell line increased under these energy-deprived conditions. The
      efflux of TPT at 37 degrees C was very rapid in the IGROV-1 as well as the
      IGROV(T100r) cell line, resulting in 90% efflux within 20 min. Importantly, the
      efflux rates of TPT in the IGROV-1 and IGROV(T100r) cell lines were not
      significantly different and were shown to be independent on P-glycoprotein (P-gp)
      or multidrug resistance-associated protein (MRP). These results strongly suggest
      that the resistance of the IGROV(T100r) cell line to TPT and SN-38 is mainly
      caused by reduced accumulation. The reduced accumulation appears to be mediated
      by a novel mechanism, probably related to impaired energy-dependent uptake of
      these topoisomerase I drugs.

PMID- 9635843
TI  - Oestrogen-regulated genes in breast cancer: association of pLIV1 with response to
      endocrine therapy.
AB  - Northern hybridization analyses of the oestrogen-inducible mRNAs pLIV1 and pS2
      were compared with oestrogen receptor (ER) immunocytochemistry assessments in 40
      untreated primary or early recurrent breast tumours. Significant associations
      were observed between pLIV1/ER (P < 0.03), pS2/ER (P < 0.001) and pLIV1/pS2 (P <
      0.04) status. After disease recurrence, patients were treated with assessable
      courses of endocrine therapies. Positive pLIV1, pS2 and ER statuses in primary
      disease were consequently found to be predictive of endocrine responsiveness in
      the secondary lesions (P < 0.03, P < 0.02, P < 0.005 respectively). However,
      despite these associations, a number of pLIV1- and/or pS2-positive tumours failed
      to respond to therapy.

PMID- 9635844
TI  - The effect of 3-week tamoxifen treatment on oestrogen receptor levels in primary
      breast tumours: a flow cytometric study.
AB  - The effect of 3-week, preoperative tamoxifen treatment on oestrogen receptor (ER)
      levels, expressed by primary breast tumours, was examined. Patients (age-matched)
      with breast cancer, confirmed by fine-needle aspiration, were either treated with
      20 mg ml(-1) oral tamoxifen per day or received no medication in the 3-week
      interval between assessment and surgery. Quantification of ER using flow
      cytometry was performed on the surgically removed tumour samples from tamoxifen
      treated (n = 40) and control (n = 38, untreated) patient groups. The tumours were
      mechanically disaggregated, and saponin treatment rendered these cells permeable
      to antibodies. Using dual-parameter labelling with a FITC-conjugated antibody
      (NCL-5D3) directed against cytokeratin 8/18/19 and a biotinylated antibody (DAKO
      ER 1D5) directed against the oestrogen receptor, ER quantification was determined
      on a number of receptors per cell basis. Using QC quantum bead standards, ER
      levels in the epithelial cell population, the non-epithelial cell population and
      the whole-cell population (ER+) were calculated. ER levels were significantly
      lower in the total cell population than tamoxifen-treated patients (P = 0.002)
      when compared with the control (untreated) group. By using a gating procedure
      using 5D3 antibody positivity, a significantly lower level was detected on
      examining the cytokeratin-positive population alone (P = 0.006). Using a
      complementary gating technique, ER levels were quantified in the cytokeratin
      negative cell population. Examination of this group of cells showed no
      significant difference between the levels of oestrogen receptor found in the
      tamoxifen-treated and untreated groups (P = 0.4). We have demonstrated that ER
      levels can be monitored by flow cytometry. ER levels in patients treated with
      tamoxifen 3 weeks before operation are significantly lower than in a comparative
      group of patients who received no drug. Furthermore, the most significant
      difference in receptor levels is seen by quantification of total ER levels
      expressed by all the tissue.

PMID- 9635845
TI  - Tissue carcinoembryonic antigen and oestrogen receptor status in breast
      carcinoma: an immunohistochemical study of clinical outcome in a series of 252
      patients with long-term follow-up.
AB  - Carcinoembryonic antigen (CEA) is a well-known tumour marker whose
      immunohistochemical expression could be prognostically relevant in breast
      carcinomas. We evaluated CEA immunohistochemical expression, using the specific
      T84.66 monoclonal antibody, in a series of 252 consecutive cases of infiltrating
      breast carcinomas (104 N0, 148 N1/2) with median follow-up of 84 months.
      Oestrogen receptor (ER) status has been evaluated with the immunohistochemical
      method (ER1D5 antibody, 10% cut-off value): 121 cases were ER negative, 128 cases
      were ER positive and in three cases ER status was unknown. CEA staining was
      cytoplasmic; staining intensity and percentage of reacting cells were combined to
      obtain a final score (CEA score). The difference between the distribution of CEA
      score within the modalities of the other variables was not statistically
      significant. Univariate survival analysis has been performed on the series of
      node-negative and node-positive patients. In the latter subgroup, this has been
      performed separately for patients treated with systemic adjuvant hormonal therapy
      or chemotherapy. A multivariate analysis was only performed for node-positive
      patients treated with adjuvant therapy. CEA immunoreactivity was not
      prognostically relevant in any subset of analysed patients. The most important
      prognostic markers were nodal status and tumour size.

PMID- 9635846
TI  - Plasma insulin-like growth factor in primary breast cancer patients treated with
      adjuvant chemotherapy.
AB  - Insulin-like growth factor 1 (IGF-1) plasma level was assayed in 60 breast cancer
      patients undergoing six courses of adjuvant chemotherapy. The only observed
      variation was a slight decrease (10%) in IGF-1 concentrations, assayed before
      treatment, between the first and the second courses of chemotherapy. During
      chemotherapy courses, there were no statistically significant variations in IGF
      1. These results suggest that chemotherapy, unlike the specific hormonal
      treatments tamoxifen and somatostatin, certainly does not act via a decrease in
      plasma IGF-1.

PMID- 9635847
TI  - High-dose therapy including carboplatin adjusted for renal function in patients
      with relapsed or refractory germ cell tumour: outcome and prognostic factors.
AB  - Thirty-one consecutive patients with relapsed or refractory GCT received an HDT
      schedule including carboplatin, the dose of which was adjusted to measured
      glomerular filtration rate. There was one HDT-associated death (3%), due to acute
      renal failure. The 3-year probability of overall and disease-free survival for 21
      patients with primary refractory disease or responsive relapse was 60% and 42%,
      respectively, while none of ten patients with refractory relapse have survived
      disease free.

PMID- 9635848
TI  - Cisplatin dose rate as a risk factor for nephrotoxicity in children.
AB  - The purpose of the study was to evaluate the incidence, risk factors and changes
      in severity with time of cisplatin nephrotoxicity in children. A total of 35
      children underwent measurement of glomerular filtration rate (GFR) and tubular
      function after completion of cisplatin chemotherapy. No child received
      ifosfamide. A clinically relevant 'nephrotoxicity score' was derived from GFR and
      serum magnesium. Follow-up studies were performed in 16 children at 1 year and in
      15 at 2 years after cisplatin. Considerable interpatient variability in
      nephrotoxicity was observed. Treatment was modified in three patients because of
      nephrotoxicity. GFR was low in 18 out of 31 patients. Proximal nephron toxicity
      caused hypomagnesaemia in ten patients and hypocalcaemia in five patients.
      Elevated urinary N-acetylglucosaminidase excretion was seen in 22 out of 30
      children, indicating subclinical tubular toxicity. Nephrotoxicity was less severe
      in children who received cisplatin courses at a dose rate of 40 mg m(-2) day(-1)
      than in those who received higher dose rates (P < 0.005), but there was no
      correlation with total dose received. Follow-up studies revealed partial recovery
      of GFR (P < 0.05). Glomerular and proximal nephron toxicity are common in
      children treated with cisplatin, and more severe at higher dose rates. Despite
      partial recovery of GFR, the long-term outcome of nephrotoxicity remains unknown
      and careful monitoring of chronic toxicity is necessary.

PMID- 9635849
TI  - Comparison of antiemetic efficacy of granisetron and ondansetron in Oriental
      patients: a randomized crossover study.
AB  - A double-blind randomized crossover trial was performed to compare the antiemetic
      efficacy of two 5-HT3 receptor antagonists, granisetron and ondansetron, in
      Chinese patients receiving adjuvant chemotherapy (cyclophosphamide, methotrexate
      and 5-fluorouracil) for breast cancer. Twenty patients were randomized to receive
      chemotherapy with either granisetron on day 1 and ondansetron on day 8 of the
      first cycle followed by the reverse order in the second cycle, or vice versa. The
      number of vomiting episodes and the severity of nausea in the first 24 h (acute
      vomiting/nausea) and the following 7 days (delayed vomiting/nausea) were studied.
      Acute vomiting was completely prevented in 29 (72.5%) cycles with granisetron and
      27 (67.5%) cycles with ondansetron, and treatment failure (>5 vomiting episodes)
      occurred in two (5%) cycles with each agent (P = NS). Acute nausea was completely
      controlled in 15 (37.5%) cycles with granisetron and 14 (35%) cycles with
      ondansetron, whereas severe acute nausea occurred in four (10%) cycles with each
      agent (P = NS). However, complete response for delayed vomiting was observed in
      only 21 (52.5%) cycles with granisetron and 22 (55%) cycles with ondansetron (P =
      NS), and delayed nausea was completely controlled in only 11 (27.5%) and ten
      (25%) cycles respectively (P = NS). In conclusion, both granisetron and
      ondansetron are effective in controlling acute nausea and vomiting in Chinese
      patients, with equivalent antiemetic efficacy. Control of delayed nausea and
      vomiting is less satisfactory.

PMID- 9635850
TI  - Neuromuscular toxicities of paclitaxel 210 mg m(-2) by 3-hour infusion.
AB  - We retrospectively analysed neuromuscular toxicity associated with paclitaxel 210
      mg m(-2) given by 3-h infusion in 247 patients. The severity correlated
      significantly with total cumulative dose, but could not be predicted by the
      pretreatment clinical variables or by pharmacokinetic parameters. The toxicity
      tended to occur in early treatment cycles.

PMID- 9635851
TI  - Treatment-induced mucositis: an old problem with new remedies.
AB  - Mucositis may be a painful, debilitating, dose-limiting side-effect of both
      chemotherapy and radiotherapy for which there is no widely accepted prophylaxis
      or effective treatment. The basis of management is pain relief, prevention of
      dehydration and adequate nutrition. When tested vigorously, most antiseptic
      mouthwashes and anti-ulcer agents are ineffective. Simple mechanical cleansing by
      saline is the most effective traditional measure. A variety of new agents are
      effective. Granulocyte macrophage colony-stimulating factor (GM-CSF) and
      granulocyte colony-stimulating factor (G-CSF) act outwith the haemopoeitic system
      and can reduce mucositis, but the best schedule, dosage and method of
      administration is not known or which is the best growth factor to prevent this
      side-effect. A placebo-controlled randomized trial of antibiotic pastilles has
      shown a significant reduction in mucositis and weight loss during radiotherapy
      for head and neck cancer. Another method to reduce radiation effects in normal
      tissue is to stimulate cells to divide before radiotherapy by silver nitrate or
      interleukin 1. These methods may be particularly effective when given along with
      hyperfractionated radiation treatment such as CHART.

PMID- 9635852
TI  - Different patterns of stromal and cancer cell thymidine phosphorylase reactivity
      in non-small-cell lung cancer: impact on tumour neoangiogenesis and survival.
AB  - Angiogenesis is recognized as an important step in tumour pathogenesis that is
      related to invasion and metastatic spread and which consequently results in poor
      clinical outcome. In this study, we have examined the role of tumour stroma
      activated fibroblasts and macrophage infiltration in the development of the
      angiogenic and metastatic phenotype in non-small-cell lung cancer (NSCLC). A
      total of 141 cases of early stage I-II NSCLC treated with surgery alone were
      analysed. The JC-70 (anti-CD31) MAb was used for the assessment of vascular
      grade. The P-GF.44C MAb was used to assess thymidine phosphorylase (TP)
      reactivity in cancer cells, stromal fibroblasts and macrophages. Cancer cell TP
      overexpression related to high vascular grade and to advanced T stage (P = 0.0004
      and P = 0.02). Expression of TP in stromal fibroblasts also correlated with high
      angiogenesis (P = 0.01), but was independent of cancer cell expression.
      Fibroblast TP overexpression was related to abundant stroma (P = 0.003),
      suggesting that TP may be a marker of active stroma. Moreover, intense macrophage
      infiltration was associated with fibroblast TP reactivity, regardless of the
      amount of stroma, suggesting that macrophages may be a major contributor to TP
      expression in stroma. Survival analysis showed that cancer cell TP overexpression
      was related to poor prognosis (P = 0.005). Although stroma TP is related to
      angiogenesis, in the low vascular grade group it defined a group of patients with
      better prognosis (P = 0.02). It may be that fibroblast TP reactivity is an
      indirect marker of tumour infiltration by functional macrophages, which have an
      antitumour effect. We conclude that stromal macrophage and fibroblast TP
      reactivity may have an important role in non-small-cell lung cancer behaviour.
      Understanding the role of stromal fibroblasts and inflammatory cells and their
      interaction with oncoprotein expression is essential for the elucidation of lung
      cancer pathogenesis.

PMID- 9635853
TI  - In oesophageal squamous cell carcinoma vascular endothelial growth factor is
      associated with p53 mutation, advanced stage and poor prognosis.
AB  - Vascular endothelial growth factor (VEGF) affects malignant tumours by promoting
      angiogenesis. The tumour-suppressor gene p53 has been thought to regulate VEGF.
      We investigated the effect of VEGF on oesophageal carcinoma and the connection
      between VEGF and p53. One hundred and nine resected oesophageal squamous cell
      carcinomas were examined. VEGF expression was analysed by immunohistochemical
      staining. Sixty-five tumours (59.6%, 65 out of 109) were classified as VEGF
      positive. A significant correlation was found between the VEGF expression and
      both the depth of invasion (P = 0.0001) and lymph node metastasis (P < 0.0001).
      With regard to p53, we compared the expression of VEGF with the mutation of p53,
      examined using polymerase chain reaction-single-strand conformation polymorphism
      (PCR-SSCP) and direct sequencing in tumour samples obtained from 36 patients who
      we have reported previously. The VEGF expression was significantly correlated to
      p53 mutation (P = 0.0291). To evaluate the angiogenesis, microvascular density
      (MVD) was counted, and endothelial cells were stained immunohistochemically using
      anti-CD34 monoclonal antibody against 29 cases with invasion limited to the
      submucosal layer. The average MVD had a tendency to correlate to VEGF expression
      (P = 0.1626). The prognoses of patients with VEGF-positive primary tumours were
      significantly worse than for those with VEGF-negative primary tumours (P =
      0.0077). We have assumed that VEGF contributes to aggressive characteristics in
      oesophageal carcinomas and that VEGF expression might be affected by p53 status.

PMID- 9635854
TI  - Encephalopathy, lactic acidosis, hyperammonaemia and 5-fluorouracil toxicity.

PMID- 9635855
TI  - The multifaceted roles of nitric oxide in cancer.
AB  - The roles of nitric oxide (NO) in numerous disease states have generated
      considerable discussion over the past several years. NO has been labeled as the
      causative agent in different pathophysiological mechanisms, yet appears to
      protect against various chemical species such as those generated under oxidative
      stress. Similarly, NO appears to exert a dichotomy of effects within the
      multistage model of cancer. Chronic inflammation can lead to the production of
      chemical intermediates, among them NO, which in turn can mediate damage to DNA.
      Yet, NO also appears to be critical for the tumoricidal activity of the immune
      system. Furthermore, NO can also have a multitude of effects on other aspects of
      tumor biology, including angiogenesis and metastasis. This report will discuss
      how the chemistry of NO may impact the initiation and progression stages of
      cancer.

PMID- 9635856
TI  - COX-2 expression is induced by UVB exposure in human skin: implications for the
      development of skin cancer.
AB  - Extensive documentation has validated the role of UV irradiation as a tumor
      initiator and promoter, inducing both squamous and basal cell carcinomas. Human
      epidermis is a tissue which undergoes active metabolism of arachidonic acid to
      prostaglandins which is regulated by the action of prostaglandin H synthase (also
      known as cyclooxygenase). One mechanism for the promotional activity of UV light
      may involve its ability to induce prostaglandin formation. Work in our laboratory
      has demonstrated that acute exposure of human keratinocytes to UVB irradiation
      results in increased production of prostaglandin E2 (PGE2). When cultured human
      keratinocytes were examined after irradiation with 30 mJ/cm2 UVB in vitro,
      Western blot analysis showed a 6-fold increase in COX-2 protein which was evident
      at 6 h and peaked 24 h after irradiation. Furthermore, when human subjects were
      irradiated on sun-protected skin with up to four times their minimal erythema
      dosage (MED) and biopsied 24 h later, upregulation of COX-2 protein expression
      was observed via immunofluorescence microscopy. RNAase protection assays
      supported this observation, showing induction of COX-2 message which peaked at
      approximately 12 h following irradiation in vitro. Furthermore, human squamous
      cell carcinoma biopsies exhibited strongly enhanced staining for COX-2 protein
      via immunohistochemistry and Western analysis when compared to normal non-sun
      exposed control skin. Together, these data demonstrate acute upregulation of COX
      2 via UVB irradiation and suggest the need for further studies of COX-2
      expression as a potential pharmacological target mediating human skin tumor
      development.

PMID- 9635857
TI  - DNA adducts, mutant frequencies and mutation spectra in lambda lacZ transgenic
      mice treated with N-nitrosodimethylamine.
AB  - Groups of lambda lacZ transgenic mice were treated i.p. with N
      nitrosodimethylamine (NDMA) as single doses of 5 mg/kg or 10 mg/kg or as 10 daily
      doses of 1 mg/kg and changes in DNA N7- or O6-methylguanine or the repair enzyme
      O6-alkylguanine-DNA alkyltransferase (AGT) were followed for up to 14 days in
      various tissues. Adduct induction in the liver exceeded by at least one order of
      magnitude than observed in the next nearest target tissue (lung), and was
      approximately linearly related to dose, except for O6-methylguanine after the
      first dose of 1 mg/kg which was lower than expected. Substantial induction of
      lambda lacZ mutagenesis was observed only in the liver, where the mutant
      frequency was already maximal within 7 days after 5 mg/kg NDMA and remained
      unchanged thereafter up to 49 days. Small but marginally significant increases in
      mutant frequency were consistently observed in the spleen after all three modes
      of treatment. A lack of proportionality between mutation induction and the
      administered dose or the corresponding adduct levels was observed, probably
      reflecting the importance of toxicity-related cell proliferation caused by NDMA
      at higher doses. Twenty eight days after a dose of 10 mg/kg (causing a 3.6-fold
      increase in mutant frequency), NDMA was found to increase the frequency of GC-
      >AT mutations (with a concomitant shift of their preferential location from CpG
      sites to GpG sites), which made up approximately 60% of the induced mutations.
      Surprisingly, NDMA also caused a significant increase in deletions of a few (up
      to 11) base-pairs (22%).

PMID- 9635858
TI  - Ultraviolet-light induced p53 mutational spectrum in yeast is indistinguishable
      from p53 mutations in human skin cancer.
AB  - Ultraviolet (UV) light has been associated with the development of human non
      melanoma skin cancers (NMSC). Such cancers often exhibit mutations in the p53
      tumour suppressor gene. In order to determine the UV-induced p53 mutation
      spectrum, a yeast expression vector that harbours a human wild-type p53 cDNA was
      UV-irradiated in vitro and transfected into a yeast strain that contained the
      ADE2 gene regulated by a p53-responsive promoter. Forty-five mutant clones
      contained 51 mutations. Seven mutations were tandem base pair substitutions, four
      of which being CC-->TT, hallmark mutations of UV mutagenesis. Eighty percent
      (41/51) of the mutations were single or non-tandem base pair substitutions, the
      majority of which (27/41) were C-->T transitions. Ninety-five percent of such
      mutations occurred at dipyrimidine sites. Through a rigorous statistical test,
      the UV-induced p53 mutation spectrum appears to differ significantly (P < 0.008)
      from the one induced by the antineoplastic drug chloroethyl-cyclohexyl
      nitrosourea, and to be indistinguishable from the one observed in NMSC (P = 0.4).
      These results demonstrate that the assay allows the determination of carcinogen
      specific p53 mutation fingerprints and represents a new tool for molecular
      epidemiology.

PMID- 9635859
TI  - Restored gap junctional communication in non-tumorigenic HeLa-normal human
      fibroblast hybrids.
AB  - Gap junctional intercellular communication (GJIC) has been implicated in
      homeostasis, development, differentiation, wound healing or regeneration and
      adaptive responses of differentiated cells. The dysfunction of homologous or
      heterologous GJIC has been associated with the tumorigenic phenotype. Restoration
      of growth control and the suppression of the tumorigenic phenotype have been
      previously associated with the up-regulation of GJIC by various anti-tumorigenic
      chemicals or transfection of connexin genes into tumor cells. To test the
      hypothesis that 'tumor suppressor' genes may be associated with the up-regulation
      of GJIC, we tested clones of tumorigenic HeLa, several non-tumorigenic HeLa
      normal human fibroblast somatic cell hybrids and a tumorigenic segregant of one
      of the non-tumorigenic hybrids for GJIC. The parental HeLa cells (D98 AH.2) had
      no detectable GJIC but expressed detectable connexin 43 transcripts, while the
      non-tumorigenic HeLa-human fibroblast hybrids, which contained the chromosome 11
      from the normal human fibroblast (CGL-1, CGL-2, ESH15 and EHS15c1), expressed
      ample connexin 43 transcripts and showed proficient GJIC. The tumorigenic
      segregant (CGL-3) from the non-tumorigenic HeLa-human fibroblast hybrid showed no
      GJIC or connexin 43. These results show that the presence of GJIC is closely
      linked to the suppression of the tumorigenic phenotype in the HeLa-human
      fibroblast hybrid and further suggest that GJIC may be associated with the
      mechanisms of tumor suppression. The mechanism by which the tumor suppressor
      gene(s) on the normal chromosome in the HeLa-human fibroblasts induces the up
      regulation of connexin 43 is not yet explained.

PMID- 9635860
TI  - Sequence specific mutations induced by N-nitrosodimethylamine at two marker loci
      in metabolically competent human lymphoblastoid cells.
AB  - N-Nitrosodimethylamine (NDMA) is a potent mutagen and animal carcinogen to which
      many people are exposed through the consumption of contaminated food and the use
      of tobacco products. Although the mutational specificity of NDMA has been studied
      in bacteria, little is known about the specific types of mutations induced by
      NDMA in the human genome. Knowledge of the mutational spectrum of NDMA in human
      genes may help to substantiate the role of NDMA in the etiology of human cancers.
      In the current study, the mutational spectrum of NDMA was characterized at the tk
      and hprt loci, in human lymphoblastoid cells capable of metabolically activating
      NDMA. A number of patterns were observed among NDMA-induced mutations. At both
      marker loci, G:C-->A:T transitions dominated the mutational spectrum of NDMA,
      which were indicative of the mutagenicity of the O6meG lesion. In addition, the
      majority of G:C-->A:T mutations occurred at guanines 3' to another guanine.
      Almost all of these mutations originated on the non-transcribed strand, which
      suggests that transcription-coupled repair influenced the distribution of G:C-
      >A:T transitions at the tk and hprt loci. Furthermore, the observation of
      hotspots for G:C-->A:T mutations, within both loci, suggests that differential
      repair kinetics may exist, and consequently affect the distribution of mutations.
      Finally, a comparison of the site specificity of G:C-->A:T mutations at the tk
      and hprt loci, indicated that the gene used for mutational analysis influenced
      the site specificity of NDMA-induced mutations, and possibly reflects the number
      of 5'-GG-3' sites in the tk and hprt loci that when mutated would yield a mutant
      phenotype.

PMID- 9635861
TI  - Defining the minimal portion of the retinoblastoma protein that serves as an
      efficient substrate for cdk4 kinase/cyclin D1 complex.
AB  - We have determined the minimal portion of the retinoblastoma protein (Rb) that
      can serve as an efficient substrate for in vitro phosphorylation by cdk4 kinase
      D1 cyclin. Kinetic measurements indicate that in vitro, a 15-kDa fragment that
      represents the C-terminus of Rb can serve equally well as a substrate when
      compared with the larger 56-kDa fragment of Rb, which contains the A, B and C
      domains. By comparison, peptide substrates appear to be 1000-fold less efficient.
      Furthermore, mutational analysis indicates that not all of the five
      phosphorylation sites within this minimal C domain are phosphorylated equally by
      cdk4/D1. Ser795 is the preferred phosphorylation site, whereas the four remaining
      sites Ser807, Ser811, Thr821 and Thr826 are phosphorylated to a much lesser
      degree. Truncations of the C domain from the carboxy terminus indicate that
      almost all of this domain is required for efficient phosphorylation. These data
      suggest that the structural context of the phosphorylation site within the
      substrate is critical for its phosphorylation by the cdk4/D1 kinase.

PMID- 9635862
TI  - Functional characterization of the human CYP1A1 negative regulatory element:
      modulation of Ah receptor mediated transcriptional activity.
AB  - The mechanisms that underly the regulation of human CYP1A1 have merited
      considerable attention because of their association both with toxic outcomes and
      the etiology of several cancers. Previous work conducted in this laboratory has
      identified a negative regulatory element (NRE) in the 5' region of this gene that
      appeared to modulate CYP1A1 transcriptional activity. This NRE is present in two
      functional copies, a high affinity 21-bp palindrome centered at position -784,
      and an additional element found within a GC-rich region between position -728 and
      -558. In this report, the regulatory function of the NREs in the context of the
      CYP1A1 promoter was evaluated. This was accomplished by substituting mutated
      elements for the corresponding wild-type element in a vector that contained human
      CYP1A1 sequences positions -1140 to +59 directing the transcription of the
      chloramphenicol acetyltransferase reporter gene. Expression vectors containing
      specific mutations in each or both NREs were characterized. We show that
      eliminating the binding of the CYP1A1 repressor protein to one or both repressor
      motifs results in a significant 2- to 3-fold increase in the inducibility of
      CYP1A1 promoter activity. Although mutation of both sites appeared to result in
      an increase in inducibility over that observed with only one site mutated, the
      effect was not additive. Such aberrant transcriptional activity correlates with
      the highly inducible aryl hydrocarbon hydroxylase phenotype that is a reported
      marker for individuals predisposed to lung cancer. Mutation of the NRE, or more
      likely, the cognate repressor protein(s), may provide a genetic basis for this
      phenotype.

PMID- 9635863
TI  - The nuclear concentration of kin17, a mouse protein that binds to curved DNA,
      increases during cell proliferation and after UV irradiation.
AB  - UV-irradiation induces, in mammalian cells, the expression of a set of genes
      known as the 'UV-response', which may be reminiscent of the bacterial response,
      called SOS system. The multifunctional protein RecA controls the expression of
      the SOS genes. We report the expression profile of a mouse gene conserved among
      mammals, called Kin17, that codes a DNA-binding protein of undetermined
      biochemical activity and which shares epitopes with the bacterial RecA protein.
      We demonstrate that the level of Kin17 RNA was 5-fold higher in mid-S phase of
      serum-stimulated BALB/c 3T3 fibroblasts than in quiescent cells. Cells in S-phase
      displayed a high level of kin17 protein with a marked nuclear localisation. The
      maximal level of Kin17 RNA was observed 18 h after serum stimulation, indicating
      that Kin17 gene is a new member of the late growth-related genes. The
      accumulation of kin17 protein during cell proliferation follows the increase in
      Kin17 RNA and correlates with DNA synthesis, which suggests a possible role of
      kin17 protein in a transaction related to DNA-replication. In quiescent
      fibroblasts, a 3-fold increase in Kin17 RNA was seen 13 h after UV irradiation.
      In parallel, kin17 protein accumulated in the nucleus, which suggests that it
      might be required after the stress produced by UV irradiation.

PMID- 9635864
TI  - Neocarzinostatin-induced mutations at the hprt locus in exponentially growing CHO
      cells, compared with spontaneous mutations.
AB  - Spontaneous mutations and neocarzinostatin-induced mutations were investigated in
      the hypoxanthine-guanine phosphoribosyltransferase (hprt) gene in exponentially
      growing Chinese hamster ovary cells. Neocarzinostatin (NCS) treatment caused an
      4.5-fold increase in mutation frequency. Analysis by multiplex polymerase chain
      reaction and sequencing of hprt cDNA revealed that spontaneous mutations in this
      system were characterized by a relatively high rate of large deletions and double
      base substitutions, and a low rate of splice mutations compared with data
      reported in fibroblastic cell lines. NCS hardly affected this spectrum of
      spontaneous mutations, which indicates the rare incidence of NCS-specific change
      in the exponential growth phase. This is in contrast to aprt gene mutations
      reported in plateau phase cells in which base substitutions occur preferentially
      at sites affected by NCS. These results suggest that differences in the loci
      assayed or in the processes involved in mammalian mutagenesis in the exponential
      growth phase and the plateau phase may be the source of the different results.

PMID- 9635865
TI  - The cellular stress response induced by aqueous extracts of cigarette smoke is
      critically dependent on the intracellular glutathione concentration.
AB  - Mainstream cigarette smoke (CS) trapped in phosphate-buffered saline solutions
      (smoke-bubbled PBS) has been shown to induce a strong stress response in cultured
      cells. This is reflected, for example, by the expression of stress genes such as
      c-fos and haem oxygenase, a transient decrease in the translation efficiency and
      the induction of cell cycle arrest. In these studies, peroxynitrite, the reaction
      product of nitric oxide (NO) and superoxide (O2-.), was identified as an active
      principle formed by CS in aqueous solutions. In the present study, we show that
      the CS-induced stress response is critically dependent on the intracellular
      glutathione (GSH) content which itself becomes diminished in cells exposed to
      smoke-bubbled PBS. Investigations using c-fos expression as a measure for
      cellular stress revealed a direct correlation between the smoke-bubbled PBS
      concentration necessary for stress-dependent c-fos expression and the
      intracellular GSH concentration observed in different cell lines.
      Correspondingly, 3T3 fibroblasts artificially depleted of GSH by pretreatment
      with buthionine-sulphoximine (BSO), an inhibitor of GSH synthesis, require
      significantly lower amounts of smoke-bubbled PBS to obtain a detectable c-fos
      expression, whereas, supplementation of the medium with N-acetyl-cysteine is an
      efficient treatment for the inhibition of a CS-induced c-fos response. We also
      show that the smoke-bubbled PBS-dependent loss of intracellular GSH is mainly
      attributable to the aldehyde fraction of CS, although these aldehydes by
      themselves cannot induce c-fos in these cells. The smoke-bubbled PBS-dependent c
      fos response can, however, be mimicked when peroxynitrite and CS-related
      aldehydes, at the concentrations calculated to appear in smoke-bubbled PBS, are
      used in combination for cell exposure. Taken together, these results suggest that
      in cells exposed to aqueous extracts of CS, smoke-related aldehydes decrease the
      intracellular GSH content significantly, allowing peroxynitrite to interfere with
      specific target molecules resulting in the stress-specific expression of c-fos.

PMID- 9635866
TI  - Mutation analysis of the Smad2 gene in human colon cancers using genomic DNA and
      intron primers.
AB  - In mammals, one of the Mad homologues, Smad2, was reported to be a mediator of
      TGF-beta signaling, and was found mutated in some cases of colon and lung
      cancers. To extend the analysis of this gene, we previously investigated the
      genomic organization of the human Smad2 gene and defined the structure of 12
      exons and flanking introns. In this study, we designed 11 sets of intron-based
      primers to examine the entire coding region of the Smad2 gene. By the PCR-SSCP
      method using these primers, we screened genomic DNA sequences of colorectal
      cancers for mutations of the Smad2 gene. Though there was no mutation within all
      exons of the Smad2 gene, two of 60 sporadic colorectal cancers displayed
      deletions in the polypyrimidine tract preceding exon 4. Deletions of this region
      were also detected in colon cancer cell lines, and were clustered within cells
      exhibiting microsatellite instability. Deletions in the polypyrimidine tract had
      various effects on pre-mRNA splicing, but had no effect on the splicing of the
      Smad2 gene in these cases. However, our data support the idea that the
      polypyrimidine tract in the splicing acceptor site is a target of mutations in
      mismatch repair-deficient tumors.

PMID- 9635867
TI  - Responses of alveolar macrophages and epithelial type II cells to oxidative DNA
      damage caused by paraquat.
AB  - Because lung cells are inevitably exposed to chemicals, drugs and mineral
      particles, they are appropriate target cells for investigating effects of
      environmental toxins. We have studied alveolar macrophages and epithelial type II
      pneumocytes freshly isolated from the rat lung, using the comet assay to detect
      DNA damage (strand breaks and oxidized bases) in individual cells after treatment
      with the pesticide paraquat. The background level of strand breaks is five times
      higher in freshly isolated pneumocytes than in alveolar macrophages. This
      difference remains even after 48 h of in vitro culture and therefore probably
      does not reflect trauma suffered during isolation. In contrast, endogenous
      formamidopyrimidine glycosylase- and endonuclease III-sensitive sites, which are
      specific indicators of oxidative damage, are present in freshly isolated alveolar
      macrophages but not in pneumocytes, reflecting the high metabolic activity of
      macrophages and their defensive role. Both cell types are exquisitely sensitive
      to strand breakage by paraquat. In addition, specific base oxidation is detected
      after 24 h of treatment with paraquat, especially in alveolar macrophages.
      Susceptibility to DNA damage, rather than lipid peroxidation, is likely to be the
      cause of paraquat-induced death in these cells. The relatively high level of
      endogenous damage in pneumocytes suggests that these cells are inefficient at DNA
      repair, which would be consistent with their probable role as the principal
      progenitors of lung cancer.

PMID- 9635869
TI  - Differences in aromatic-DNA adduct levels between alveolar macrophages and
      subpopulations of white blood cells from smokers.
AB  - The 32P-post-labelling assay for DNA adduct quantification gives the opportunity
      to examine endogenous exposure to DNA reactive compounds. Most human
      biomonitoring studies applied white blood cells (WBC) or cells obtained by
      broncho-alveolar lavages (BAL) as source of DNA, but still it is not clear what
      cell type represents the most reliable indicator for exposure to cigarette smoke
      associated genotoxins. At first, we examined DNA adduct levels by means of
      nuclease P1 (NP1) enriched 32P-post-labelling in separated WBC subpopulations
      after in vitro incubations for 18 h with 10 microM benzo[a]pyrene (B[a]P). DNA
      adduct levels were highest in monocytes (10.7 +/- 2.9 adducts/10(8) nucleotides,
      n = 8), followed by lymphocytes (5.9 +/- 1.7, n = 8), and granulocytes (0.5 +/-
      0.2, n = 8). Secondly, aromatic-DNA adduct levels were determined in BAL cells
      and WBC-subsets from (non-)smoking volunteers. In smoking individuals, adduct
      levels were in the ranking order: BAL cells (3.7 +/- 1.0, n = 5) > monocytes (2.0
      +/- 0.5, n = 8) > or = lymphocytes (1.6 +/- 0.4, n = 8) > granulocytes (0.8 +/-
      0.2, n = 8) by NP1-enrichment and monocytes (9.0 +/- 3.2, n = 5) > or =
      lymphocytes (8.0 +/- 2.1, n = 6) > granulocytes (2.1 +/- 0.3, n = 7) by butanol
      enriched 32P-post-labelling. Aromatic-DNA adduct levels were significantly higher
      in WBC-subsets of smokers as compared with non-smokers, except for DNA adducts in
      granulocytes using butanol enrichment. Thirdly, dose-response relationships were
      investigated in mononuclear white blood cells (MNC, i.e. monocytes plus
      lymphocytes) and BAL-cells of a larger group of smoking individuals (n = 78).
      Adduct levels in MNC were related to daily exposure to cigarette-tar (r = 0.31, P
      < 0.01). Adduct levels in BAL cells seemed to be correlated with pack-years, but
      after correction for age this relationship was lost. Butanol extraction resulted
      in 5-6-fold higher DNA adduct levels in MNC, whereas butanol extraction of BAL
      DNA of the same individuals yielded only 2-fold higher adduct levels. The two
      enrichment procedures of 32P-post-labelling were correlated in BAL cells (r =
      0.86, P < 0.001, n = 12). We conclude that particularly MNC are good surrogates
      for the detection of smoking-related DNA adducts.

PMID- 9635868
TI  - Lung cancer risk and CYP1A1 genotype in African Americans.
AB  - The role of CYP1A1 genotype in lung cancer risk was assessed in African Americans
      through a case control study. The complete CYP1A1 genotype, including the
      frequency of all three polymorphisms (Msp1 [CYP1A1*2], exon 7 [CYP1A1*3] and
      African American specific [CYP1A1*4]) was determined by PCR on 307 controls and
      105 cases of lung cancer among African Americans. We have confirmed our earlier
      observation of a significant increased risk (odds ratio = 2.8, 95% CI = 1.3-6.5)
      for lung adenocarcinoma among people with the *4 polymorphism, although we did
      not observe any association of this polymorphism with overall lung cancer risk.
      As previously reported, we found that lung adenocarcinoma patients with the *4
      RFLP smoked significantly less than patients without this polymorphism,
      suggesting an important role in cancer risk of low exposure levels to cigarette
      smoke in subjects carrying susceptibility polymorphisms. There was no association
      with the other two polymorphisms and lung cancer in this population. When we
      examined lung cancer risk as a function of composite genotype, taking into
      account all three polymorphisms simultaneously in each subject, our preliminary
      data suggested an association of one rare genotype (homozygous Msp1, heterozygous
      exon 7 or *2/*2*3) with overall lung cancer risk (OR = 8.4, 95% CI = 1.6-43.2).

PMID- 9635870
TI  - Modulation of small G protein isoprenylation by anticancer monoterpenes in in
      situ mammary gland epithelial cells.
AB  - Monoterpenes have been shown to both prevent and treat mammary cancer in animal
      models and are currently in clinical testing in advanced cancer patients. In this
      study, we investigated a biochemical modulation associated with the antitumor
      activity of monoterpenes, the inhibition of protein isoprenylation in monoterpene
      chemoprevention target tissue, i.e. the in situ mammary gland epithelial cells.
      We first developed a new methodology that for the first time permitted the study
      of protein isoprenylation and other products in the mevalonate pathway in in situ
      mammary cells. Using this approach, we found that chronically feeding rats with
      an anticancer dose of perillyl alcohol resulted in a 22% inhibition of coenzyme Q
      synthesis and a 19% inhibition of small G protein isoprenylation in mammary gland
      epithelial cells in situ. The greatest inhibition of small G protein
      isoprenylation observed was the 28% inhibition of isoprenylation of RhoA by type
      I geranylgeranyl protein transferase (GGPTase). Given that some substrates of
      type I GGPTase, such as RhoA and Rac1, have transforming properties, the
      possibility that the inhibition of type I GGPTase will change the cellular
      location and functionality of these proteins and thus contribute to the
      chemoprevention activity of monoterpenes, is discussed.

PMID- 9635871
TI  - Maspin gene expression in tumor suppression induced by overexpressing manganese
      containing superoxide dismutase cDNA in human breast cancer cells.
AB  - We have reported the tumor suppressive effects of manganese-containing superoxide
      dismutase (MnSOD) in human breast cancer cells. In order to understand the
      molecular mechanism of this anti-tumor effect, we asked whether tumor suppressor
      gene(s), especially the ones inhibiting tumor invasion and motility, are involved
      in MnSOD-induced tumor suppression. Maspin is one of the serpin family of
      protease inhibitors that has been shown to function as a tumor-suppressor in
      human breast epithelium. In the present study, we demonstrated that maspin
      expression was up-regulated in human breast cancer MCF-7 cells that overexpress a
      normal MnSOD gene. The induced maspin transcripts were detected by RT-PCR and
      Northern blot and identified by sequencing. Maspin gene expression was induced in
      parallel with the level of exogenous MnSOD protein, which was induced by
      transfection with varied amounts of cDNA. In order to analyze cell invasion
      ability, which may be related to the induced maspin gene expression, MnSOD stable
      transfectants were tested using a matrigel invasion chamber. The invasion ability
      was reduced to 24% and 36% in the cloned (MCF + SOD) and pooled MnSOD
      transfectants (MCF + SODp) respectively, compared with the wild-type MCF-7 cell
      line. In conclusion, these results suggest that overexpression of a normal MnSOD
      cDNA in human breast cancer cells up-regulates the gene expression of the
      protease inhibitor, maspin, which may play a role in the inhibitory function of
      MnSOD on tumor invasion.

PMID- 9635872
TI  - Smoking-associated bulky DNA adducts in bronchial tissue related to CYP1A1 MspI
      and GSTM1 genotypes in lung patients.
AB  - Relationships between smoking status and levels of bulky DNA adducts were
      investigated in bronchial tissue of lung patients in relation to their GSTM1 and
      CYP1A1 MspI genotypes. A total of 150 Hungarian patients undergoing pulmonary
      surgery were included in the study, 124 with lung malignancies and 26 with non
      malignant lung conditions. There were significant relationships between smoking
      status and bulky DNA adduct levels, as determined by 32P-post-labelling analysis,
      in macroscopically normal bronchial tissues. There was a highly significant
      difference in the adduct levels of a combined group consisting of current smokers
      and short-term ex-smokers (< or = 1 year abstinence) compared with life-time non
      smokers and long-term ex-smokers (> 1 year abstinence) (P = 0.0001). The apparent
      half-life was estimated to be 1.7 years for bulky DNA adducts in the bronchial
      tissue from ex-smokers. There were no statistically significant correlations
      between (i) daily cigarette dose and DNA adduct levels in current smokers, (ii)
      DNA adduct level and histological type of lung cancer, or (iii) GSTM1 and CYP1A1
      MspI genotypes and DNA adduct levels after adjustment for either smoking status
      or malignancy. By multiple logistic regression analysis, smoking and GSTM1 null
      genotype were found to be risk factors for squamous cell carcinoma. However,
      bulky DNA adduct levels in bronchial tissue did not appear to be a statistically
      significant risk factor for the major histological types of lung cancer.

PMID- 9635873
TI  - X-ray-induced lymphomagenesis in E mu-pim-1 transgenic mice: an investigation of
      the co-operating molecular events.
AB  - Transgenic mice overexpressing the pim-1 oncogene in their lymphoid compartment
      display a low incidence of spontaneous T-cell lymphomas, but are highly
      susceptible to point mutation-inducing genotoxic carcinogens. We show here that
      total body X-irradiation, which causes mainly chromosomal deletions,
      rearrangements and amplifications, significantly enhances lymphoma development in
      E mu-pim-1 transgenic mice. The X-ray-induced E mu-pim-1 and non-transgenic
      lymphomas have a comparable high cell turnover as shown by a relatively high S
      phase fraction and a high apoptotic activity. Consistent with previous
      observations, in 75% of all lymphomas c-myc mRNA levels are 5- to 20-fold higher
      than in control, non-lymphomatous spleen/thymus. The expression of other
      oncogenes, which have previously found to be activated in combination with pim-1
      in lymphomagenesis, such as gfi-1/pal-1, frat-1 and tiam-1, and also of the mdm-2
      and mdm-x oncogenes, appeared not to be affected. Deletions and/or rearrangements
      of the p16INK4A and p15INK4B tumor suppressor genes were seldom observed (in
      three out of 92 X-ray-induced lymphomas). Strikingly, in addition to the high
      mRNA levels of the pim-1 transgene, the levels of the endogenous pim-1
      transcripts were elevated significantly in 16% of the X-ray-induced E mu-pim-1
      lymphomas compared with control spleen, even surpassing the level of the pim-1
      transgene mRNA by 3- to 5-fold. In combination with previous results, which
      showed that the lymphoma incidence increased concordantly with higher levels of
      pim-1, this supports the notion that pim-1 can contribute to lymphomagenesis in a
      dose-dependent manner.

PMID- 9635874
TI  - Clonal analysis of urothelial carcinomas in C3H/HeN<-->BALB/c chimeric mice
      treated with N-butyl-N-(4-hydroxybutyl)nitrosamine.
AB  - The histological background for multifocal and metachronous development of
      urothelial carcinomas remains equivocal, although accumulated genetic evidence
      suggests monoclonal origin of multiple urothelial carcinomas. Clonal development
      of various preneoplastic and neoplastic urothelial lesions of C3H<-->BALB/c
      chimeric mice induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was
      immunohistochemically investigated using a C3H strain-specific antibody. All
      tumor masses induced in the mice treated with 0.05% BBN for 20 weeks were
      composed of neoplastic cells of a single parental type, which is indicative of
      monoclonal lesions. Three of 10 animals harbored two or more separate carcinomas
      of different clonal type, which is indicative of multicentric development
      applicable in this model. Using DNAs derived from urothelial carcinomas and tumor
      adjacent urothelium of chimeric mice, polymerase chain reaction-single strand
      conformation polymorphism (PCR-SSCP) analysis and direct sequencing were
      performed for p53 gene exons 5-7. p53 mutations were identified in four of 11
      (36%) dysplasias and non-invasive carcinomas (carcinoma in situ and pTa tumor)
      and 13 of 22 (59%) invasive carcinomas. Only in a single case were identical p53
      mutations found in separate urinary bladder carcinomas. In contrast to the random
      distribution of urothelial proliferating units in chimeric mice without chemical
      supplement, invasive carcinomas in BBN-treated mice were accompanied by widely
      distributed preneoplastic and neoplastic lesions of the same clonality, which
      occasionally had frequent foci of microinvasion. This is indicative of lateral
      clonal expansion of the clones, which precedes the bulk of invasive carcinomas.
      Thus, two aspects of 'field change' of the urothelium became evident in this
      model: either independent transformation events or lateral clonal expansion
      might, respectively, result in multicentric and monoclonal carcinoma development
      in the urinary tract.

PMID- 9635875
TI  - The metabolic activation of tamoxifen and alpha-hydroxytamoxifen to DNA-binding
      species in rat hepatocytes proceeds via sulphation.
AB  - The biotransformation pathway of tamoxifen and alpha-hydroxytamoxifen to DNA
      binding species was investigated in rat hepatocytes in vitro. Rat hepatocytes
      were isolated by in situ collagenase perfusion and then maintained in sulphate
      free Dulbecco's modified Eagle's medium. Magnesium sulphate was added to the
      medium to give concentrations of 0-10 microM, prior to treatment for 18 h with
      solvent vehicle (DMSO), tamoxifen (10 microM), alpha-hydroxytamoxifen (1 microM)
      or benzo[a]pyrene (BaP) (10 and 50 microM). DNA was isolated and analysed by 32P
      post-labelling. For tamoxifen and alpha-hydroxytamoxifen, the level of DNA adduct
      formation was directly proportional to the concentration of sulphate in the
      medium. Between 0 and 10 microM MgSO4, the DNA adduct level increased 10-fold
      with both compounds. Rat hepatocytes were also maintained in normal Dulbecco's
      modified Eagle's medium and pretreated with dehydroisoandrosterone-3-sulphate
      (DHEAS, a sulphotransferase inhibitor) at concentrations ranging from 0-1 mM,
      prior to treatment with solvent vehicle (DMSO), tamoxifen (10 microM), alpha
      hydroxytamoxifen (1 microM) or BaP (50 microM). For tamoxifen and alpha
      hydroxytamoxifen the level of DNA adducts was reduced to approximately one-fifth
      by the addition of DHEAS (0.1 mM). BaP-DNA adduct formation, which proceeds by a
      pathway that does not require sulphation, was not significantly affected by
      sulphate concentration or by addition of DHEAS, which demonstrates that the
      general metabolic capacity and viability of the hepatocytes were not compromised.
      It is concluded that the activation of tamoxifen in rat liver cells to DNA
      binding products proceeds predominantly through hydroxylation followed by
      sulphate ester formation at the alpha-position of the ethyl side chain.

PMID- 9635876
TI  - 16Alpha-hydroxylation of estrone by human cytochrome P4503A4/5.
AB  - The cytochrome P450 (P450) enzymes that catalyse metabolism of the estrogen,
      estrone (E1), to the putative carcinogen 16alpha-hydroxy E1 (16alpha-OHE1) in
      humans were determined. The potential of the most abundant circulating form of
      estrogen, estrone 3-sulfate (E1S), to be the substrate was also investigated.
      Human liver microsomal sulfatases convert E1S to E1, an essential prerequisite
      for formation of 16alpha-OHE1 from added E1S in this system. E1 metabolism to
      16alpha-OHE1 in a panel of 15 human liver microsomal preparations correlated with
      total P450 concentrations (r2 = 0.63) and with activities associated with P450
      forms CYP3A4 and 3A5 (r2 = 0.72). E1 16alpha-hydroxylase activity in human liver
      microsomes was inhibited by 75% by monoclonal anti human CYP3A4/5 antibodies at 4
      mg antibody/nmol total P450, and by troleandomycin, a specific CYP3A4/5
      inhibitor. Rates of E1 metabolism to 16alpha-OHE1 were 1.6-fold higher when E1
      was generated in situ from E1S than when E1 was added. Microsomal preparations of
      cDNA expressed CYP3A4 or 3A5, with NADPH-P450-reductase co-expressed, both
      metabolized E1 to 16alpha-OHE1, and added cytochrome b5 increased the rates 5.1-
      and 7.5-fold, respectively. In these systems rates of E1 metabolism to 16alpha
      OHE1 were 2.8-fold higher when E1 was generated in situ from E1S than when E1 was
      added. Kinetic values for E1 metabolism to 16alpha-OHE1 by human liver microsomes
      and for the expressed CYP3A4 system were Km 154 and 172 microM, respectively, and
      Vmax 238 pmol/min/nmol total P450 and 1050 pmol/min/nmol CYP3A4, respectively.
      Thus, formation of the putative carcinogen 16alpha-OHE1 is catalysed by CYP3A4
      and 3A5 and stimulated by cytochrome b5. E1S is not a substrate but formation of
      E1 from E1S in situ stimulates formation of 16alpha-OHE1, possibly because E1S is
      more water soluble and in situ generation of E1 provides for facilitated exposure
      of E1 to the P450 substrate binding sites. Blocking of the pathway of E1 to
      16alpha-OHE1 could provide a therapeutic approach for diminishing the risk of
      estrogen dependent breast cancer.

PMID- 9635877
TI  - Interindividual variation in the metabolic activation of heterocyclic amines and
      their N-hydroxy derivatives in primary cultures of human mammary epithelial
      cells.
AB  - The heterocyclic amines, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino
      3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) and 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP) are pyrolysis products formed when meat is
      cooked and are rodent mammary carcinogens. They are thought to be metabolically
      activated by N-hydroxylation, catalysed by cytochrome P450 (CYP), followed by O
      acetylation catalysed by N-acetyltransferases. Primary cultures of human mammary
      epithelial cells (HMECs) prepared from up to 26 individuals for each compound,
      were treated with IQ, MeIQ, or PhIP (500 microM) or with N-hydroxy-2-amino-1
      methyl-6-phenylimidazo[4,5-b]pyridine (N-OH-PhIP) or N-hydroxy-2-amino-3
      methylimidazo[4,5-f]quinoline (N-OH-IQ) (20 microM) and the levels of adduct
      formation in their DNA analysed by 32P-post-labelling. In order to investigate
      whether pharmacogenetic polymorphisms influence DNA adduct formation, the NAT2
      genotype of each individual was determined by a polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) method that distinguishes
      between the wild-type and four variant alleles. Presence of two variant alleles
      designates a slow NAT2 acetylator, whereas individuals with one or two wild-type
      alleles are designated fast NAT2 acetylators. Interindividual variations in total
      DNA adduct levels ranged for IQ from 0.64-63.1 DNA adducts per 10(8) nucleotides
      (mean 7.80), for MeIQ from 1.99-17.8 (mean 6.63), for PhIP from 0.13-4.0 (mean
      0.96), for N-OH-PhIP from 6.32-497 (mean 176) and for N-OH-IQ from 0.92-30.6
      (mean 9.24). The higher adduct levels observed in cells treated with the N-OH
      metabolites suggests that N-hydroxylation is the rate-limiting step in HMECs and
      this may be due to low CYP levels. In contrast, the Phase II reaction catalysed
      by N-acetyltransferases is probably the major step in the metabolic activation of
      heterocyclic amines that occurs in the breast. Higher mean levels of heterocyclic
      amine-DNA adduct formation were detected in the cells of NAT2 fast acetylators
      compared with slow acetylators, with mean adduct levels per 10(8) nucleotides
      following IQ treatment, of 12.74 and 3.57 respectively, following PhIP treatment,
      of 1.20 and 0.74, respectively, following MeIQ treatment, of 7.90 and 5.08,
      respectively and following N-OH-PhIP-treatment, of 243.1 and 130.0, respectively.
      However, due to the large variations in adduct levels, these differences in mean
      values were not statistically significant with the limited number of individuals
      studied. This appears to be the first pilot study to demonstrate interindividual
      variations in the metabolic activation of heterocyclic amines and their metabolic
      intermediates in primary cultures of HMECs in vitro.

PMID- 9635878
TI  - Effect of 3-aminotriazole on anchorage independence and mutagenicity in cadmium-
      and lead-treated diploid human fibroblasts.
AB  - Cadmium and lead have been shown to induce cellular transformations and gene
      mutations in cultured rodent cells, as well as tumours in live animals. However,
      the mechanisms by which these metals cause cellular transformations and mutations
      in human cells have not been explored. In this study, we investigated the
      abilities of cadmium and lead to induce anchorage-independent transformations and
      hprt gene mutations in diploid human fibroblasts. Human fibroblasts were exposed
      to either cadmium acetate (0-60 microM) or lead acetate (0-2 mM) for 24 h. After
      removal of the metals, the cells were kept in exponential growth for 7 and 9 days
      before mutation and anchorage-independence assays were taken, respectively. Both
      cadmium and lead significantly induced anchorage-independent colonies in dose
      dependent manners; the frequencies of anchorage-independent colonies induced by
      these metals were similar to those induced by N-methyl-N'-nitro-N
      nitrosoguanidine at approximately equal cytotoxic dose ranges (30-10% survival).
      3-Aminotriazole at non-cytotoxic dosages decreased catalase activity by >80%, and
      markedly enhanced cadmium-induced cytotoxicity and anchorage-independent
      colonies. Cadmium uptake by human fibroblasts was not affected by 3-aminotriazole
      co-administered with 10 microM of cadmium; whereas cadmium uptake and
      accumulation were enhanced 1.5-fold by 3-aminotriazole co-administered with 1-2.5
      microM of cadmium. Lead-induced anchorage-independence or cytotoxicity was not
      affected by 3-aminotriazole co-treatment; however, 3-aminotriazole did
      significantly enhance lead uptake and accumulation in human fibroblasts. Neither
      cadmium- nor lead-induced 6-thioguanine-resistant mutation frequency in human
      fibroblasts. Co-administering these metals with 3-aminotriazole did not enhance
      mutations in human fibroblasts. These results suggest that cadmium and lead may
      both act as tumour promoters in diploid human fibroblasts, and that reactive
      oxygen species is more important in cadmium- than lead-induced cytotoxicity and
      anchorage-independence.

PMID- 9635879
TI  - Arsenite inhibits mitotic division and perturbs spindle dynamics in HeLa S3
      cells.
AB  - Arsenical compounds, known to be human carcinogens, were shown to disturb cell
      cycle progression and induce cytogenetic alterations in a variety of cell
      systems. We report here that a 24 h treatment of arsenite induced mitotic
      accumulation in human cell lines. HeLa S3 and KB cells were most susceptible: 35%
      of the total cell population was arrested at the mitotic stage after treatment
      with 5 microM sodium arsenite in HeLa S3 cells and after 10 microM in KB cells.
      Under a microscope, we observed abnormal mitotic figures in arsenite-arrested
      mitotic cells, including deranged chromosome congression, elongated polar
      distance of mitotic spindle, and enhanced microtubule immunofluorescence. The
      spindle microtubules of arsenite-arrested mitotic cells were more resistant to
      nocodazole-induced dissolution than those of control mitotic cells. According to
      turbidity assay, arsenite at concentrations below 100 microM significantly
      enhanced polymerization of tubulins. Since spindle dynamics play a crucial role
      in mitotic progression, our results suggest that arsenite-induced mitotic arrest
      may be due to arsenite's effects on attenuation of spindle dynamics.

PMID- 9635880
TI  - Over-expression of glutathione S-transferase Yp isozyme and concomitant down
      regulation of Ya isozyme in renal cell carcinoma of rats induced by ferric
      nitrilotriacetate.
AB  - An iron chelate, ferric nitrilotriacetate (Fe-NTA), induces renal proximal
      tubular damage, a consequence of iron-catalysed Fenton-like reactions, that
      finally leads to a high incidence of renal cell carcinoma (RCC) in rodents.
      Glutathione S-transferase (GST) is a family of enzymes that play an important
      role in detoxification of hydrophobic and electrophilic molecules, and has been
      associated with putative preneoplastic foci of rat hepatocarcinogenesis and
      chemotherapy-resistance of human cancers. Our previous study revealed an
      induction of pi-class glutathione S-transferase (Yp) mRNA in the kidney 3 h after
      administration of Fe-NTA. In the present study, expression of GST isozymes were
      further investigated in the Fe-NTA-induced RCCs of rats which are characterized
      by (1) high incidence of metastasis and invasion, (2) high incidence of tumour
      associated mortality, and (3) possible involvement of reactive oxygen species in
      carcinogenesis. In the Fe-NTA-induced RCCs, the levels of alpha-class GST (Ya)
      mRNA and proteins were markedly decreased with no apparent change in the copy
      number of the gene. In contrast, GST-Yp mRNA and proteins were significantly
      increased in the RCCs while the total GST enzymatic activity was decreased.
      Immunohistochemical analysis revealed intense staining of GST-Yp not only in the
      primary RCCs and its metastatic sites, but also in their non-tumorous part of
      proximal tubules. The contrastive expression of GST isozymes in this renal
      carcinogenesis model suggests an alteration of its transcription mechanisms and
      warrants further investigation of this particular detoxifying enzyme from the
      viewpoint of reactive oxygen species-induced carcinogenesis.

PMID- 9635881
TI  - The effect of dietary n-3 and n-6 polyunsaturated fatty acids on the expression
      of cyclooxygenase 1 and 2 and levels of p21ras in rat mammary glands.
AB  - Dietary n-6 polyunsaturated fatty acids (PUFAs) promote rat mammary cancer while
      n-3 PUFAs are inhibitory. The purpose of this study was to determine whether the
      fats exert their effects by altering the expression of genes that affect cancer
      development. Therefore, we have examined the effect of PUFAs on the expression of
      the cyclooxygenase (COX) 1 and 2 genes that are involved in prostaglandin
      biosynthesis. We also investigated the effect of dietary PUFAs on the expression
      of the p21ras protein and Ha-ras mRNA. Rats were fed either low- (7%; LF) or high
      (21%; HF) fat diets that were rich in either n-6 PUFAs (safflower oil, S) or n-3
      PUFAs (menhaden oil, M) for 3 weeks. COX-1 mRNA levels were approximately the
      same in groups fed diets containing either level of menhaden oil, but were
      increased by approximately 30% in the LFS and HFS groups (P < 0.05). Transcripts
      of the inducible COX-2 gene were not detectable in the menhaden oil groups, but
      this gene was expressed in animals fed either level of safflower oil and in the
      HFS group was associated with increased levels of COX enzymatic activity and
      production of PGE2. Animals fed safflower oil had elevated levels of p21ras
      protein compared to animals fed menhaden oil. Ha-ras mRNA was increased by
      approximately 35% in animals fed HFS compared to the group fed HFM (P < 0.05).
      These results demonstrate that dietary n-6 PUFAs upregulate COX-2 and, to some
      extent, COX-1 expression. There was a concomitant increase in COX enzyme activity
      and PG synthesis in the mammary glands of rats fed high levels of n-6 PUFAs.
      Together with associated changes in p21ras expression, these results may explain,
      at least in part, the promoting effects of dietary n-6 PUFAs on mammary
      carcinogenesis.

PMID- 9635882
TI  - N'-(3'-monophospho-deoxyguanosin-8-yl)-N-acetylbenzidine formation by
      peroxidative metabolism.
AB  - N'-(3'-Monophospho-deoxyguanosin-8-yl)-N-acetylbenzidine (dGp-ABZ) is thought to
      play an important role in initiation of benzidine-induced bladder cancer in
      humans. This report assesses the possible formation of this adduct by peroxidatic
      activation of N-acetylbenzidine (ABZ). Adduct formation was measured by 32P-post
      labeling. Ram seminal vesicle microsomes were used as a source of prostaglandin H
      synthase (PHS). The peroxidatic activity of PHS was compared with that for
      horseradish peroxidase. Both peroxidases converted ABZ to dGp-ABZ whether DNA or
      2'-deoxyguanosine 3'-monophosphate (dGp) was present. Following 32P-post
      labeling, the enzymatic and synthetic adduct were extracted from PEI-cellulose
      plates and were shown to have the same HPLC elution profiles for the bisphosphate
      adduct (32P-dpGp-ABZ). Treatment of the enzymatic and synthetic bisphosphate
      adduct with nuclease P1 yielded a product that eluted at the same time from the
      HPLC (32P-dpG-ABZ). Additional experiments demonstrated that the PHS-derived 5'
      monophosphate (dpG-ABZ) and 3'-monophosphate (dGp-ABZ) adducts were also
      identical to their corresponding synthetic standard. With comparable amounts of
      total ABZ metabolism, PHS produced approximately 40-fold more dGp-ABZ than
      horseradish peroxidase (1943 +/- 339 versus 49 +/- 7.8 fmol/mg dGp). Adduct
      formation was dependent upon the presence of peroxidase and the specific
      substrate, i.e. arachidonic acid or H2O2. Adduct formation by PHS was inhibited
      by indomethacin (0.1 mM), ascorbic acid (1 mM) and glutathione (10 mM), but not
      by 5,5-dimethyl-1-pyrroline N-oxide (DMPO) (100 mM), a radical scavenger.
      Horseradish peroxidase adduct formation was also inhibited by ascorbic acid and
      glutathione. In addition, DMPO elicited greater than a 96% inhibition. Results
      demonstrate peroxidatic metabolism of ABZ to form dGp-ABZ. The mechanism of dGp
      ABZ formation by PHS and horseradish peroxidase may be different.

PMID- 9635883
TI  - Distribution and metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
      (PhIP) in female rats and their pups at dietary doses.
AB  - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mammary carcinogen in
      female rats and is present in a wide variety of cooked meats. We address here the
      excretion of PhIP and its metabolites into the breast-milk of lactating rats and
      the ability of chlorophyllin, a food product derivative with chemopreventive
      properties, to affect these levels at low PhIP doses. Lactating female F344 rats
      with suckling pups were orally administered 50, 500 and 1000 ng [14C]PhIP/kg body
      weight. The excretion of the [14C]PhIP into milk and its distribution among the
      mammary tissue, liver and blood of the dam, as well as among stomach contents and
      liver of their suckling pups was measured using accelerator mass spectrometry
      (AMS). PhIP, PhIP-4'-sulfate, 4'-hydroxy-PhIP, and N2-hydroxy-PhIP-N3-glucuronide
      were found in the milk at all doses. The chlorophyllin (500 microg/kg) co
      administration with PhIP (500 ng/kg) caused increased levels of [14C]PhIP in the
      milk (32%) and stomach contents (35%) of the pups relative to the animals not
      receiving chlorophyllin at these low PhIP doses. In contrast, lower [14C]PhIP
      levels in the chlorophyllin treated animals were observed in the blood (47%) and
      mammary tissue (68%) of the dam, as well as the pup's liver tissue (37%) compared
      to the animals receiving only PhIP. Chlorophyllin co-administration resulted in
      an increased amount of N2-hydroxy-PhIP-N3-glucuronide (42%), increased PhIP (79%)
      and decreased levels of PhIP-4'-sulphate (77%) relative to the animals not
      receiving chlorophyllin. These results suggest that PhIP and PhIP metabolites are
      present in the breast-milk of lactating rats at human dietary PhIP exposures and
      that PhIP is absorbed by the newborn. Furthermore, these results suggest that
      other dietary components can affect the dosimetry of PhIP in breast-feeding
      offspring.

PMID- 9635884
TI  - The peroxisome proliferators are hepatocyte mitogens in chemically-defined media:
      glucocorticoid-induced PPAR alpha is linked to peroxisome proliferator
      mitogenesis.
AB  - Peroxisome proliferator-induced mitogenesis is believed to play a role in
      hepatocarcinogenesis, but it has not been possible to demonstrate high level
      induction of DNA synthesis by peroxisome proliferators in cultured hepatocytes.
      We now show that four structurally dissimilar peroxisome proliferators
      (methylclofenapate, Wy-14 643, tetradecyl-3-thia acetic acid and clofibrate)
      cause high level induction of DNA synthesis in primary cultures of rat
      hepatocytes, routinely 7-9 fold above control, with up to 29% of cells undergoing
      S-phase. Peroxisome proliferators induce DNA synthesis rapidly, with maximal
      response 24 h after dosing [compared with 48 h for epidermal growth factor
      (EGF)]; indeed, peroxisome proliferators were mitogenic in a chemically defined
      medium, i.e. with no added exogenous growth factors. EGF-treated hepatocytes that
      had undergone DNA synthesis comprised 23% binucleated cells, whereas hepatocytes
      induced into S-phase by peroxisome proliferators contained only 3% binucleated
      cells, demonstrating a distinct response of hepatocytes to peroxisome
      proliferators and EGF. The presence of a glucocorticoid was essential for
      peroxisome proliferator-induced DNA synthesis, but not for EGF-induced DNA
      synthesis, demonstrating that the requirement for glucocorticoids is selective
      for peroxisome proliferators. Hydrocortisone was shown to induce the expression
      of peroxisome proliferator activated receptor-alpha (PPAR alpha), and we propose
      that it is the glucocorticoid-induced expression of PPAR alpha that is essential
      for peroxisome proliferator mitogenesis. This in vitro system provides a powerful
      tool for investigating the mechanism and role of peroxisome proliferator-induced
      mitogenesis in liver growth and carcinogenesis.

PMID- 9635885
TI  - Caffeine-derived N-nitroso compounds. V. Carcinogenicity of mononitrosocaffeidine
      and dinitrosocaffeidine in bd-ix rats.
AB  - Mononitrosocaffeidine (MNC) and dinitrosocaffeidine (DNC) are new N-nitroso
      compounds obtained from in vitro nitrosation of caffeidine, a hydrolysis product
      of caffeine present in a typically made and widely consumed tea from Kashmir
      (India), a high incidence area of esophageal and stomach cancer. The chemical
      synthesis, in vitro metabolic studies and mutagenicity of the compounds has been
      previously reported. DNC, a nitrosamide is highly mutagenic both with and without
      metabolic activation whereas MNC, like several other aromatic asymmetric
      nitrosamines, does not exhibit genotoxic or mutagenic properties. We now report
      the results of the first carcinogenicity experiments on chronic oral
      administration of these compounds in BD-IX rats. The acute LD50 of MNC and DNC
      were about 1300 and 230 mg/kg b.w., respectively. Lung oedema and
      gastrointestinal haemorrhages were the first symptoms of intoxication observed
      after 2 days for both the compounds. All three dose groups of MNC treated rats
      showed localization of tumours in nasal cavity (93.9-100% of all malignant
      tumours). The tumours were histologically diagnosed as neuroepitheliomas of the
      olfactory epithelium (neuroblastoma of the bulbus olfactorii) and squamous cell
      carcinoma of the nasal cavity in the ratio of 3:1. No tumours of the nasal cavity
      were observed in the untreated controls. DNC, in contrast, induced squamous cell
      carcinoma of forestomach in 100% animals at low and high doses, of which nearly
      half the tumours metastasized predominantly into the peritoneum. No forestomach
      tumours were seen in the untreated controls. The data presented here clearly show
      the potential for induction of malignant tumours and distinct organ-specificity
      by MNC and DNC in rats, and support the postulate that a chronic exposure to
      these compounds may provide a carcinogenic risk for high incidence of
      gastrointestinal cancers in Kashmir.

PMID- 9635886
TI  - 2,3-epoxy-4-hydroxynonanal, a potential lipid peroxidation product for etheno
      adduct formation, is not a substrate of human epoxide hydrolase.
AB  - Our previous studies have shown that 2,3-epoxy-4-hydroxynonanal, a reactive epoxy
      aldehyde capable of forming etheno adducts with DNA bases, is mutagenic and
      tumorigenic (Carcinogenesis, 14, 2073). The epoxy aldehyde can be generated from
      trans-4-hydroxy-2-nonenal, a lipid peroxidation product of omega-6
      polyunsaturated fatty acids, by autoxidation or by incubation with fatty acid
      hydroperoxides or hydrogen peroxides (Chem. Res. Toxicol., 9, 306). These are
      plausible in vivo pathways for the formation of 2,3-epoxy-4-hydroxynonanal. The
      possibility that 2,3-epoxy-4-hydroxynonanal is a tumorigen of endogenous origin
      is suggested by recent observations that etheno bases are detected as background
      DNA lesions in untreated rodents and humans. A metabolic pathway critical for
      detoxification of 2,3-epoxy-4-hydroxynonanal involves the ring-opening by epoxide
      hydrolase, which abolishes its ability to form cyclic etheno DNA adducts. In this
      study, we examined whether 2,3-epoxy-4-hydroxynonanal is a substrate of cDNA
      expressed human epoxide hydrolase. Human epoxide hydrolase was expressed in TK-
      143 cells (thymidine kinase-deficient human embryoblast) infected with
      recombinant vaccinia virus encoding human epoxide hydrolase cDNA. Controls
      consisted of the cells infected with vaccinia virus in the absence of human
      epoxide hydrolase cDNA. No hydrolysis occurred when [2,3-(3)H]2,3-epoxy-4
      hydroxynonanal was incubated at 37 degrees C for 30 min at pH 7.4 with cells
      expressing human epoxide hydrolase, as indicated by the presence of a pair of
      radioactive peaks in reversed-phase HPLC chromatography, which comigrated with
      the UV standards of the two diastereomers of the epoxy aldehyde. The identity of
      these compounds as the intact epoxy aldehyde was further supported by
      derivatization to the 2,4-dinitrophenylhydrazones followed by reversed phase HPLC
      analysis. Similar results were observed with the control cells or with the heat
      deactivated human epoxide hydrolase. The epoxide hydrolase activity in the
      expressed cells was demonstrated by their ability to convert benzo[a]pyrene-4,5
      dihydroepoxide to benzo[a]pyrene-trans-4,5-dihydrodiol under the same conditions.
      These results clearly indicate that 2,3-epoxy-4-hydroxynonanal is not a substrate
      of human epoxide hydrolase, and, thus strengthen its possible endogenous role in
      the formation of promutagenic exocyclic etheno adducts in vivo.

PMID- 9635887
TI  - Identification, chromosomal mapping and tissue-specific expression of hREV3
      encoding a putative human DNA polymerase zeta.
AB  - The Saccharomyces cerevisiae REV3 gene encodes the catalytic subunit of a non
      essential DNA polymerase zeta, which is required for mutagenesis. The rev3
      mutants significantly reduce both spontaneous and DNA damage-induced mutation
      rates. We have identified human cDNA clones from two different libraries whose
      deduced amino acid sequences bear remarkable homology to the yeast Rev3, and
      named this gene hREV3. The hREV3 gene was mapped to chromosome 1p32-33 by
      fluorescence in situ hybridization. The hREV3 encodes an mRNA of >10 kb, and its
      expression varies in different tissues and appears to be elevated in some but not
      all of the tumor cell lines we have examined. In light of recent reports of a
      putative mouse REV3, these results indicate that mammalian cells may also contain
      a mutagenic pathway which aids in cell survival at the cost of increased
      mutation.

PMID- 9635888
TI  - Molecular characterization of ST1C1-related human sulfotransferase.
AB  - Carcinogenic arylamines such as N-hydroxy-2-acetylaminofluorene (N-OH-AAF) are
      metabolically activated by mammalian sulfotransferases to form N-hydroxyarylamine
      O-sulfates. We previously showed that rat ST1C1 efficiently mediate these
      activations. These reactions occur in liver cytosols of humans as well as rats.
      However, the enzyme responsible for N-OH-AAF activation has not been identified
      in humans. In the present study, a human cDNA (ST1C2) encoding a sulfotransferase
      showing a high similarity with ST1C1, has been isolated from a human fetal liver
      cDNA library and expressed using a bacterial expression system. A clear
      difference was observed in the pH optima for p-nitrophenol sulfation between
      ST1C2 and ST1C1 expressed in Escherichia coli. In addition, ST1C2 did not mediate
      3'-phosphoadenosine-5'-phosphosulfate-dependent DNA binding of N-OH-AAF. These
      results suggest that human ST1C2 has a clear different substrate specificity, in
      spite of the structural similarity, with rat ST1C1.

PMID- 9635889
TI  - Callosal terminals in the rat prefrontal cortex: synaptic targets and association
      with GABA-immunoreactive structures.
AB  - The callosal projections of the cerebral cortex play an important role in the
      functional integration of the two hemispheres, and the anatomy of these
      connections has been extensively studied in primary sensory and motor regions. In
      the present investigation, we examined the synaptic targets of callosal terminals
      in a limbic association area, the prefrontal cortex (PFC) in the rat. In
      addition, we examined the relationship of callosal afferents to GABA local
      circuit neurons within the PFC. Callosal terminals were labeled by either
      anterograde transport of Phaseolus vulgaris leucoagglutinin from superficial or
      deep layers or by anterograde degeneration following electrolytic lesion of the
      contralateral PFC. Callosal terminals in either the superficial or deep layers
      labeled by either method formed primarily asymmetric axo-spinous synapses
      (approximately 95%), while the remainder formed axo-dendritic synapses. Some of
      the dendrites postsynaptic to callosal terminals exhibited a morphology
      characteristic of local circuit neurons. This observation was confirmed in tissue
      immunolabeled for GABA, in which degenerating callosal terminals sometimes formed
      asymmetric synapses on GABA-labeled dendrites. In addition, GABA-labeled
      terminals and callosal afferents were sometimes observed to converge onto common
      postsynaptic dendritic shafts or spines within the PFC. These results indicate
      that callosal terminals in limbic association cortex, consistent with sensory and
      motor cortices, primarily target the spines of pyramidal neurons. In addition,
      the results suggest that callosal afferents to the PFC interact with GABA local
      circuit neurons at multiple levels. Specifically, a proportion of callosal
      terminals appear to provide excitatory drive to GABA cells, while GABA terminals
      may modulate the excitation from callosal inputs to the distal dendrites and
      spines of PFC pyramidal neurons.

PMID- 9635890
TI  - Effects of overexpression of the cytoplasmic copper-zinc superoxide dismutase on
      the survival of neurons in vitro.
AB  - The cytoplasmic copper-zinc superoxide dismutase (Cu, Zn SOD; SOD-1) is an
      abundant and well-conserved intracellular antioxidant enzyme which has been
      implicated in a number of oxidative stress mediated phenomena, especially Down
      Syndrome, in which SOD-1 activity is increased due to triplication of chromosome
      21 containing the gene and, in hereditary amyotrophic lateral sclerosis, in which
      the gene is mutated. Overexpression of SOD-1 could theoretically, therefore, lead
      to increased vulnerability to oxidative stress in two distinct manners:
      increasing steady-state hydrogen peroxide levels or increasing toxic side
      reactions. We used two mouse neuronal culture systems--one in which the murine
      chromosome containing SOD-1 is triplicated and one in which human SOD-1 is a
      transgene--to test the effect of overexpression of this enzyme on antioxidant
      status in general and specifically on glutamate mediated oxidative stress. We
      found that SOD-1 overexpression increases antioxidant status at the same time it
      decreases vulnerability to glutamate.

PMID- 9635891
TI  - Selective blockade of a slowly inactivating potassium current in striatal neurons
      by (+/-) 6-chloro-APB hydrobromide (SKF82958).
AB  - The ion channels of rat striatal neurons are known to be modulated by stimulation
      of D1 dopamine receptors. The susceptibility of depolarization-activated K+
      currents to be modulated by the D1 agonist, 6-chloro-7,8-dihydroxy-3-allyl-1
      phenyl-2,3,4,5-tetra-hydro-1H-3-benzaze pine (APB) was investigated using whole
      cell voltage-clamp recording techniques from acutely isolated neurons. APB (0.01
      100 microM) produced a concentration-dependent reduction in the total K+ current.
      At intermediate concentrations (ca. 10 microM), APB selectively depressed the
      slowly inactivating A-current (I(As)). A similar effect was produced by
      application of the D1 agonist, 7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1-H-2
      benzazepine (SKF38393, 10 microM). APB reduced I(As) rapidly, having onset and
      recovery time constants of 1.2 sec and 1.6 sec, respectively. Unexpectedly, the
      effect of APB could not be mimicked by application of Sp-adenosine 3',5'-cyclic
      monophosphothioate triethylamine (Sp-cAMPS, 100-200 microM), a membrane-permeable
      analog of cyclic AMP (cAMP), or by pretreatment with forskolin (25 microM), an
      activator of adenylyl cyclase. The reduction in I(As) also was not blocked by
      pretreatment with the D1 receptor antagonist, R(+)-SCH23390 hydrochloride
      (SCH23390, 10-20 microM). In addition, intracellular dialysis with guanosine-5'-O
      (2-thiodiphosphate (GDP-beta-S, 200 microM) did not preclude the APB-induced
      inhibition of I(As), nor did dialysis with guanosine-5'-O-(3-thiotriphosphate
      (GTP-gamma-S, 400 microM) prevent reversal of the effect. The effect of APB was
      produced by a reduction in the maximal conductance of I(As) without changing the
      voltage-dependence of the current. Collectively, these results argue that APB
      does not inhibit I(As) through D1 receptors coupled to stimulation of adenylyl
      cyclase, but rather by allosterically regulating or blocking the channels giving
      rise to this current.

PMID- 9635892
TI  - 6-[18F]Fluoro-L-DOPA PET studies of the turnover of dopamine in MPTP-induced
      parkinsonism in monkeys.
AB  - This report describes a method to assess, in vivo, the turnover of dopamine (DA)
      and describes its application to the evaluation of DA function in normal monkeys
      and monkeys with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced
      lesions of the DA nigro-striatal pathway. Using positron emission tomography with
      the tracer of presynaptic DA function, 6-[18F]fluoro-L-DOPA (FDOPA), and an
      extension of the graphical method of analysis, we measured the striatal FDOPA
      uptake rate constant, Ki, and the rate of reversibility of FDOPA trapping k(loss)
      in normal and MPTP-treated monkeys, either neurologically normal or displaying a
      parkinsonian symptomatology. An index of effective DA turnover was defined as the
      ratio of k(loss)/Ki. Compared to normal controls, Ki was decreased and k(loss)
      was increased in the MPTP-lesioned monkeys. The index of DA turnover was
      significantly increased in the monkeys displaying a parkinsonian symptomatology
      as compared to the controls and the neurologically normal MPTP-treated monkeys.
      The DA turnover index was also significantly increased in the neurologically
      normal MPTP-lesioned animals compared to normals. This suggests that an increase
      in DA turnover develops early in the disease process and may be one of the
      compensatory mechanisms partly responsible for the delay in the development of
      the clinical manifestations in Parkinson's disease.

PMID- 9635893
TI  - Ng-nitro-L-arginine, an NOS inhibitor, reduces tolerance to morphine in the rat
      locus coeruleus.
AB  - Ng-nitro-L-arginine (L-NArg), a potent nitric oxide synthase inhibitor, has been
      implicated as a potential mechanism for attenuating the development of tolerance
      to opioid drugs and for suppressing opioid withdrawal. Neurons in the locus
      coeruleus (LC) express opioid receptors and these neurons exhibit both tolerance
      to chronic administration of opioids and antagonist-precipitated withdrawal
      hyperactivity. This study tested the hypothesis that L-NArg would attenuate the
      development of opioid tolerance in LC neurons. Challenge doses of morphine were
      administered while recording single-cell extracellular activity in brain slices
      from rats who had been concurrently treated for 5 days with morphine (75 mg
      morphine sulfate base pellets) and L-NArg (10 mg/kg, i.p., bid). The average ED50
      for morphine of cells from rats who received L-NArg injections and morphine
      pellets was similar to that in cells from rats who had been implanted with sham
      pellets (14.5-18 nM). In contrast, the average ED50 of cells from morphine
      pelleted animals who received saline injections was substantially higher (34.5
      nM). These results demonstrate that L-NArg attenuates the development of
      tolerance to morphine in LC neurons.

PMID- 9635894
TI  - Ultrastructural localization of mu-1 opioid receptor in the dorsal raphe nucleus
      of the rat.
AB  - A simple pre-embedding avidin-biotin-peroxidase complex technique was used to
      study the ultrastructural localization of mu-1 opioid receptor in the rat dorsal
      raphe nucleus. Using low concentrations of the first antiserum for incubation
      with a short reaction time to 3,3'-diaminobenzidine, the immunostaining was faint
      at the light microscopic level. However, at the electron microscopic level strong
      immunoreaction was observed. Mu-1 opioid receptors were found to be localized on
      the postsynaptic membrane of dendrites, extra-synaptic plasma membrane, and the
      surface of the small, clear vesicles in axon terminals. Of the total 407
      immunopositive profiles observed, 76.4% (311/407) were dendrites and 18.9%
      (77/407) were axon terminals. The immunostained myelinated axons and perikarya
      were relatively rare, with frequencies of 1.0% (4/407) and 3.7% (15/407),
      respectively. About 50.8% of the immunopositive dendrites (158/311) were
      immunostained having their MOR-LI results beneath the postsynaptic membrane,
      although about 19.6% of them (31/158) also exhibited MOR-LI on other components,
      including the extrasynaptic plasma membrane. Other immunopositive dendrites
      showed staining in some other contents, including extrasynaptic plasma membrane
      (82/311, 26.4%) or not on the plasma membranes (71/311, 22.8%). Less than half of
      the immunopositive axon terminals (35/77, 45.5%) were found to make synapses with
      nonimmunoreactive dendrites (31/77, 40.3%) or immunopositive dendrites (4/77,
      5.2%); none were found to make synapses with immunoreactive perikarya. The
      present study shows that mu-1 opioid receptor in the dorsal raphe nucleus plays a
      role at both synapse or not.

PMID- 9635895
TI  - Differential inhibition of catecholamine secretion by amitriptyline through
      blockage of nicotinic receptors, sodium channels, and calcium channels in bovine
      adrenal chromaffin cells.
AB  - We investigated the effects of amitriptyline, a tricyclic antidepressant, on
      [3H]norepinephrine ([3H]NE) secretion and ion flux in bovine adrenal chromaffin
      cells. Amitriptyline inhibited [3H]NE secretion induced by 1,1-dimethyl-4
      phenylpiperazinium iodide (DMPP) and 70 mM K+. The half maximal inhibitory
      concentration (IC50) was 2 microM and 9 microM, respectively. Amitriptyline also
      inhibited the elevation of cytosolic calcium ([Ca2+]i) induced by DMPP and 70 mM
      K+ with IC50 values of 1.1 microM and 35 microM, respectively. The rises in
      cytosolic sodium ([Na+]i) and [Ca2+]i induced by the Na+ channel activator
      veratridine were also inhibited by amitriptyline with IC50 values of 7 microM and
      30 microM, respectively. These results suggest that amitriptyline at micromolar
      concentrations inhibits both voltage-sensitive calcium (VSCCs) and sodium
      channels (VSSCs). Furthermore, submicromolar concentrations of amitriptyline
      significantly inhibited DMPP-induced [3H]NE secretion and [Ca2+]i rise, but not
      veratridine- or 70 mM K+-induced responses, suggesting that nicotinic
      acetylcholine receptors (nAChR) as well as VSCCs and VSSCs can be targeted by
      amitriptyline. DMPP-induced [Na+]i rise was much more sensitive to amitriptyline
      than the veratridine-induced rise, suggesting that the influx of Na+ and Ca2+,
      through the nAChR itself is blocked by amitriptyline. Receptor binding
      competition analysis showed that binding of [3H]nicotine to chromaffin cells was
      significantly affected by amitriptyline at submicromolar concentrations. The data
      suggest that amitriptyline inhibits catecholamine secretion by blocking nAChR,
      VSSC, and VSCC.

PMID- 9635896
TI  - Inhibition of NMDA-receptor mediated response in the rat medial prefrontal
      cortical pyramidal cells by the 5-HT3 receptor agonist SR 57227A and 5-HT:
      intracellular studies.
AB  - The techniques of intracellular recording and single-electrode voltage-clamp were
      used to study the effect of serotonin (5-HT) and the selective 5-HT3 receptor
      agonist SR 57227A on N-methyl-D-aspartic acid (NMDA)-evoked responses in
      pyramidal cells of the rat medial prefrontal cortex (mPFC) in in vitro brain
      slice preparations. Bath application of 5-HT or SR 57227A produced a
      concentration-dependent inhibition of NMDA-induced membrane depolarization,
      action potentials, and inward current. The depressant action of 5-HT and SR
      57227A had a slow onset and showed no signs of receptor desensitization. This
      action was markedly attenuated or completely blocked by the selective 5-HT3
      receptor antagonists granisetron and BRL 46470A, but not other receptor
      antagonists. In addition to inhibiting NMDA-evoked responses, SR 57227A also
      depressed significantly pharmacologically isolated, NMDA receptor-mediated,
      monosynaptic excitatory postsynaptic currents (EPSCs) elicited by electrical
      stimulation of the forceps minor; this inhibitory action was blocked by BRL
      46470A but not other 5-HT receptor antagonists. Perfusion of Ca2+-free or low
      Ca2+ plus Cd2+ artificial cerebrospinal fluid prevented electrical stimulation
      induced EPSCs, but did not affect the inhibitory action of 5-HT and SR 57227A. In
      conclusion, we demonstrate for the first time that 5-HT and SR 57227A interact
      with 5-HT3-like receptors to produce a direct inhibitory action on NMDA receptor
      mediated response in pyramidal cells of the mPFC.

PMID- 9635897
TI  - Differential effects of chronic haloperidol administration on midbrain dopamine
      neurons in Sprague-Dawley, Fischer 344, and Lewis rats: an in vivo
      electrophysiological study.

PMID- 9635898
TI  - Acute and chronic administration of clozapine produces greater proconvulsant
      actions than haloperidol on focal hippocampal seizures in freely moving rats.
AB  - In this study, we assessed the effects of the acute (a single injection) and
      repeated (once daily injections for 21 days) administration of the atypical
      antipsychotic drug clozapine (1.5, 5, or 15 mg/kg i.p.) and the typical
      antipsychotic drug haloperidol (0.15, 0.5, and 1.5 mg/kg, i.p.) on hippocampal
      partial seizures generated by low-frequency electrical stimulation in male Wistar
      rats. The seizure threshold and severity were determined by measuring the pulse
      number threshold (PNT) and the primary afterdischarge duration (ADD),
      respectively. A single injection of either 5 or 15 mg/kg of clozapine
      significantly decreased the PNT and significantly increased the primary ADD,
      indicating a proconvulsant action. The repeated administration of clozapine (1.5,
      5, or 15 mg/kg, i.p.) produced dose-dependent, proconvulsant effects by
      significantly decreasing the PNT and by significantly increasing the primary ADD.
      In contrast to clozapine, the acute administration of haloperidol did not
      significantly alter the PNT or the primary ADD. The repeated administration of
      haloperidol (0.5 and 1.5 mg/kg, i.p.), unlike clozapine, significantly decreased
      the primary ADD, but did not alter the PNT. Overall, clozapine produces a greater
      proconvulsant action than haloperidol in an animal model of hippocampal seizures.

PMID- 9635899
TI  - Immature chemodifferentiation of Purkinje cell synapses revealed by 5'
      nucleotidase ecto-enzyme activity in the cerebellum of the reeler mouse.
AB  - During postnatal development of the rodent cerebellum, a transient enzyme
      activity of ecto-5'-nucleotidase has been shown in the asymmetrical synapses of
      Purkinje cells. The alterations of the afferent circuitry and microenvironment of
      the ectopic Purkinje cells present in the cerebellum of the reeler mutant mouse
      could enlighten parameters that influence the synaptic 5'-nucleotidase activity
      of these cells. Ecto-enzyme cytochemistry reveals intense 5'-nucleotidase
      activity in 43% of synapses of the Purkinje cells throughout the cortex and the
      core of the reeler cerebellar vermis, although the molecular layer displays large
      areas with less than 1% of labelled synapses. However, enzymatic labelling is
      found in considerably more Purkinje cells synapses (73%) throughout the granular
      layer and the subcortical mass. Climbing fiber synapses of monoinnervated
      Purkinje cells are labelled by 5'-nucleotidase activity in the molecular layer,
      as well as asymmetrical synapses made on the subjacent ectopic Purkinje cells by
      the multiple climbing fibers and by the heterologous afferences. The non
      innervated dendritic spines of these cells are also labelled, suggesting that 5'
      nucleotidase activity at postsynaptic sites of reeler Purkinje cells does not
      depend on the presynaptic innervation. Rather, 5'-nucleotidase enzyme activity is
      enhanced at theses sites when the Purkinje cells have not achieved
      chemodifferentiation but have conserved immature wiring, i.e., low parallel fiber
      and multiple climbing fiber inputs.

PMID- 9635900
TI  - Acanthamoeba keratitis.
AB  - Acanthamoeba species are an important cause of microbial keratitis that may cause
      severe ocular inflammation and visual loss. The first cases were recognized in
      1973, but the disease remained very rare until the 1980s, when an increase in
      incidence mainly associated with contact lens wear was reported. There is an
      increased risk when contact lens rinsing and soaking solutions are prepared with
      nonsterile water and salt tablets. The clinical picture is often characterized by
      severe pain with an early superficial keratitis that is often treated as herpes
      simplex infection. Subsequently a characteristic radial perineural infiltration
      may be seen, and ring infiltration is common. Limbitis and scleritis are
      frequent. Laboratory diagnosis is primarily by culture of epithelial samples
      inoculated onto agar plates spread with bacteria. Direct microscopy of samples
      using stains for the cyst wall or immunostaining may also be employed. A variety
      of topically applied therapeutic agents are thought to be effective, including
      propamidine isethionate, clotrimazole, polyhexamethylene biguanide, and
      chlorhexidine. Various combinations of these and other agents have been employed,
      often resulting in medical cure, especially if treatment is commenced early in
      the course of the disease. Penetrating keratoplasty is preferably avoided in
      inflamed eyes, but may be necessary in severe cases to preserve the globe or,
      when the infection has resolved, to restore corneal clarity for optical reasons.

PMID- 9635901
TI  - Assessment of human ocular hemodynamics.
AB  - Vascular abnormality and altered hemodynamics play important roles in many
      ophthalmic pathologies. Much of our knowledge of ocular hemodynamics was gained
      from invasive animal research, although a number of noninvasive methods suitable
      for in vivo use in humans have been developed. Data from these methods now
      produce a significant literature of their own. Understanding the origins of the
      data and appreciating their limitations can be difficult. Modern hemodynamic
      assessment techniques each examine a unique facet of the ocular circulation. No
      single facet provides a complete description of the hemodynamic state of the eye.
      These methods have contributed a great deal to our understanding of normal
      hemodynamics. More importantly, they continue to add to our understanding of
      altered hemodynamics found in disease. Some have found their way into limited
      clinical practice. The predominant ocular hemodynamic assessment techniques are
      reviewed with the aims of introducing the fundamental principles behind each,
      highlighting their inherent advantages and limitations, highlighting their
      contributions to understanding ocular physiology, and considering their potential
      to provide signs for diagnosis.

PMID- 9635902
TI  - The association between cigarette smoking and ocular diseases.
AB  - Tobacco smoke is composed of as many as 4,000 active compounds, most of them
      toxic on either acute or long-term exposure. Many of them are also poisonous to
      ocular tissues, affecting the eye mainly through ischemic or oxidative
      mechanisms. The list of ophthalmologic disorders associated with cigarette
      smoking continues to grow. Most chronic ocular diseases, with the possible
      exception of diabetic retinopathy and primary open-angle glaucoma, appear to be
      associated with smoking. Both cataract development and age-related macular
      degeneration, the leading causes of severe visual impairment and blindness, are
      directly accelerated by smoking. Other common ocular disorders, such as retinal
      ischemia, anterior ischemic optic neuropathy, and Graves ophthalmopathy, are also
      significantly linked to this harmful habit. Tobacco smoking is the direct cause
      of tobacco-alcohol amblyopia, a once common but now rare disease characterized by
      severe visual loss, which is probably a result of toxic optic nerve damage.
      Cigarette smoking is highly irritating to the conjunctival mucosa, also affecting
      the eyes of nonsmokers by passive exposure (secondhand smoking). The dangerous
      effects of smoking are transmitted through the placenta, and offspring of smoking
      mothers are prone to develop strabismus. Efforts should be directed toward
      augmenting the campaign against tobacco smoking by adding the increased risk of
      blindness to the better-known arguments against smoking. We should urge our
      patients to quit smoking, and we must make them keenly aware of the afflictions
      that can develop when smoke gets in our eyes.

PMID- 9635903
TI  - The Francis I. Proctor Foundation: the first fifty years.
AB  - September 15, 1997 marked the golden anniversary of the Francis I. Proctor
      Foundation, which was established in affiliation with the University of
      California in San Francisco. Over 50 years, 182 fellows from 27 countries have
      been trained in programs focusing on the study of infectious and inflammatory eye
      disease, and the prevention of blindness worldwide. Many of the people and events
      that have contributed to the success of the Proctor Foundation are presented in
      this brief essay.

PMID- 9635904
TI  - Drug-induced uveitis.
AB  - Uveitis has been reported in association with a variety of topical, intraocular,
      periocular, and systemic medications. To establish causality of adverse events by
      drugs, in 1981, Naranjo and associates proposed seven criteria, which are related
      to the frequency and documentation of the event; circumstances of occurrence,
      recovery, and recurrence; and coexistence of other factors or medications. Rarely
      does a drug meet all seven criteria. The authors review reports of drug
      associated uveitis, applying the seven criteria and examining possible
      mechanisms. Only systemically administered biphosphonates and, perhaps, topical
      metipranolol meet all seven criteria. Systemic sulfonamides, rifabutin, and
      topical glucocorticoids fulfill at least five criteria.

PMID- 9635905
TI  - The child with divergence paresis.
AB  - Divergence paralysis is a rare clinical entity that causes a comitant esotropia
      at distance. While this is usually benign and self-limited, there are reports of
      divergence paralysis associated with brain tumors, central nervous system
      syphilis, trauma, and multiple sclerosis. We studied a 14-year-old girl who
      presented with diplopia and was found to have divergence paralysis. Magnetic
      resonance imaging disclosed a large pontomedullary glioma.

PMID- 9635906
TI  - Comparison of six rapid agglutination tests for the identification of
      Staphylococcus aureus, including methicillin-resistant strains.
AB  - Six rapid agglutination tests for the identification of Staphylococcus aureus
      were evaluated by testing 416 strains of staphylococci. The sensitivities and
      specificities of the tests were as follows: Staphyloslide, 97.7% and 99.3%
      respectively; Prolex Staph Latex, 96.9% and 93.6%; Staphaurex, 95.4% and 94.2%;
      Staphaurex Plus, 100% and 93.4%; Slidex Staph Plus, 98.9% and 99.3%; and
      Staphytect Plus, 99.6% and 88.2%. The three tests utilizing latex particles
      coated with staphylococcal capsular antibodies were better able to identify
      methicillin-resistant S. aureus, but only Staphyloslide and Slidex Staph Plus had
      adequate specificity.

PMID- 9635907
TI  - Optimal recovery of cytomegalovirus from urine as a function of specimen
      preparation.
AB  - Cytomegalovirus (CMV) is a significant pathogen among immunocompromised patients.
      We compared supernatant and sediment fractions of centrifuged urine for the
      optimal recovery of CMV by shell vial culture and polymerase chain reaction
      (PCR). Of 336 urine specimens, 31 (9.23%) were positive by shell vial culture; of
      these 29 (93.5%) were identified using the sediment fraction and 17 (54.8%) using
      the supernatant fraction (p = 0.001, chi2). Of the 29 positive sediment fraction
      specimens, 24 (82.8%) were identified as CMV positive at 24 h and 5 (17.2%) were
      identified as positive at 48 h. Two (0.064%) of the total 31 positive specimens
      were lost to microbial contamination in the sediment inoculated cultures. Of the
      17 supernatant fraction specimens, 9 (53.9%) were identified as CMV positive at
      24 h and 8 (47.1%) were identified as positive at 48 h. Fourteen (45.2%) of the
      total 31 positive specimens were lost to either toxicity or microbial
      contamination in the sediment-inoculated cultures. Thirty-four CMV culture
      positive specimens were tested by PCR; 5 of these specimens (14.7%) were PCR
      negative for both sediment and supernatant fractions; 26 (76.5%) were found to be
      positive using the sediment fraction and negative using the supernatant; 3 (8.8%)
      were PCR positive for both the sediment and the supernatant. None of the 34 was
      identified as positive using the supernatant fraction only (p = 0.001, chi2).
      These findings demonstrate that the method of specimen preparation can
      significantly affect the outcome of diagnostic testing for CMV from urine
      specimens.

PMID- 9635908
TI  - In vitro activities of six fluoroquinolones against Canadian isolates of
      vancomycin-sensitive and vancomycin-resistant Enterococcus species.
AB  - The in vitro activities of six fluoroquinolones were determined against 1482
      Enterococcus species isolates collected as part of a 1996 Canadian surveillance
      study. Clinafloxacin MIC90s were 4 or 8 microg/mL, trovafloxacin and BAY 12-8039
      MIC90s were 8 or 16 microg/mL, sparfloxacin MIC90s were 32 microg/mL, and
      ciprofloxacin and ofloxacin MIC90s were >32 microg/mL for the vancomycin
      sensitive Enterococcus faecalis, vancomycin-sensitive Enterococcus faecium, and
      vancomycin-resistant E. faecium isolates collected.

PMID- 9635909
TI  - Comparative antimicrobial activity and kill-curve investigations of novel
      ketolide antimicrobial agents (HMR 3004 and HMR 3647) tested against Haemophilus
      influenzae and Moraxella catarrhalis strains.
AB  - The activity of two ketolide compounds, HMR 3004 and 3647, were compared to those
      of five macrolides, quinupristin/dalfopristin, ciprofloxacin, and ampicillin. The
      rate of killing for the ketolides was also assessed against Haemophilus
      influenzae and Moraxella catarrhalis. One hundred H. influenzae and 148 M.
      catarrhalis isolates were tested using broth microdilution and appropriate growth
      media. The killing rates of HMR 3004 and 3647 were analyzed using the time-kill
      method against five strains from each of the two species. Against H. influenzae,
      the activity of the ketolides (MIC90, 2 or 4 microg/mL) resembled that of
      azithromycin and quinupristin/dalfopristin and was more active than any tested
      macrolide. Against M. catarrhalis, HMR 3004 and 3647 were equally potent as
      azithromycin and clarithromycin (MIC50, 0.06 microg/mL and MIC90, 0.12 microg/mL)
      and more potent than all other macrolides or quinupristin/dalfopristin. Time-kill
      kinetic studies revealed that like the macrolide compounds, the ketolides are
      bacteristatic at or near the MIC for both H. influenzae and M. catarrhalis. This
      activity can be increased to a bactericidal level if the concentration is
      increased four- or eightfold the MIC for H. influenzae. In conclusion, HMR 3004
      and 3647 have bacteristatic activity against tested respiratory pathogens and may
      prove to have an important role against macrolide-resistant isolates.

PMID- 9635910
TI  - Piperacillin/tazobactam versus imipenem: a double-blind, randomized formulary
      feasibility study at a major teaching hospital.
AB  - With the introduction of piperacillin/tazobactam to the North American market,
      hospitals have been faced with the task of making a decision regarding its
      formulary role. In view of its broad spectrum of activity,
      piperacillin/tazobactam could be considered as a formulary alternative to
      imipenem. To evaluate the formulary feasibility of substituting
      piperacillin/tazobactam for imipenem, a comparative assessment of these agents in
      the empiric treatment of serious bacterial infections was undertaken at this
      tertiary care hospital. This trial was conducted as a randomized, double-blind,
      single-center study. Consenting adult patients (>16 years of age) who were
      prescribed imipenem were randomized to receive either 4 g of i.v.
      piperacillin/tazobactam or imipenem 500 mg of i.v. Q6H with or without concurrent
      antibiotics. Doses were adjusted according to renal function. There were no
      restrictions regarding the use of nonstudy antibiotics before and during the
      study period. Patients with beta-lactam allergies or meningitis or who had
      received greater than 72 h of previous imipenem therapy were excluded. Patients
      were evaluated at the end of treatment, at discharge, and at 30 days
      postdischarge. Endpoints included both clinical and microbiologic efficacy as
      well as drug toxicity. Over the 433-day study period, 360 imipenem treatment
      courses were initiated. Of these, 150 treatment courses (75
      piperacillin/tazobactam courses and 75 imipenem courses) met study criteria and
      were subsequently randomized. The distribution of prescriber services for
      enrolled patients was similar to that for all patients receiving imipenem during
      the study period (p = 0.15). Also, there were no statistically significant
      differences in demographic parameters between enrolled and excluded patients. For
      those patients enrolled in the study, demographic characteristics, treatment
      course indication(s), and accompanying antibiotics were similar across treatment
      arms. The mean duration of study drug therapy was 7.7 days (SD, 6.2) for imipenem
      and 7.5 days (SD, 6.7)for piperacillin/tazobactam (p = 0.84). In the majority of
      cases, treatment discontinuation occurred as a result of a favorable treatment
      course outcome, stepdown to a narrower spectrum parenteral agent, or stepdown to
      an oral agent and did not differ between study drugs (p = 0.73). Clinical and
      microbiologic treatment course outcomes were also similar across treatment arms.
      Clinical outcome was deemed successful or improved for 68% of imipenem and 70% of
      the piperacillin/tazobactam treatment courses (p = 0.54). Fifty-three percent of
      treatment courses were microbiologically confirmed. Of the 58 courses that were
      assessed for microbiological outcome, 93% demonstrated successful eradication of
      the causative pathogens. There was no difference between study drugs (96%
      imipenem; 90% piperacillin/tazobactam; p = 0.61). The proportion of treatment
      courses with at least one adverse event was similar between the study drugs (p =
      1.0). Nausea and/or vomiting were/was observed more commonly in the imipenem arm
      (p = 0.03). Discontinuation of therapy due to drug toxicity occurred in 16% of
      imipenem and 5% of piperacillin/tazobactam treatment courses (p = 0.06). There
      was no statistically significant difference between the mean treatment course
      cost for imipenem ($762; range, $55-$3192) versus piperacillin/tazobactam ($696;
      range, $79-$2967; p = 0.59). In summary, piperacillin/tazobactam seems to
      represent a suitable alternative to imipenem for several clinical indications
      including intraabdominal infections, pneumonia, febrile neutropenia, and
      skin/soft tissue infections in which the causative pathogens are susceptible.
      However, in view of the prevalence of multiresistant Gram-negative aerobic
      pathogens at this institution, we do not believe that imipenem can be removed
      from the drug formulary. In addition, at the currently studied dosing regimen,
      there seems to be no evidence of a direct cost advantage associated with

PMID- 9635911
TI  - AIDS-related Mycobacterium kansasii infection with initial resistance to
      clarithromycin.
AB  - Clarithromycin is a promising drug for the treatment of Mycobacterium kansasii
      infection. We report a patient with AIDS and severe M. kansasii infection who had
      previously received a short course of clarithromycin for sinusitis. He had
      clinical failure of treatment using clarithromycin plus ethambutol, and the
      initial isolate was found to be highly resistant to clarithromycin. Nucleotide
      sequencing of the 23S rRNA gene of this isolate demonstrated a single base
      mutation at position 2058, the same as that found in clarithromycin-resistant
      Mycobacterium avium.

PMID- 9635912
TI  - Combinations of orally administered beta-lactams to maximize spectrum and
      activity against drug-resistant respiratory tract pathogens: I. Synergy studies
      of amoxicillin and cefixime with Streptococcus pneumoniae.
AB  - Streptococcus pneumoniae strains have emerged that are resistant to penicillin
      (MICs >0.06 microg/mL) and many other beta-lactams. However, some older compounds
      such as amoxicillin have potency against these pneumococci with altered
      penicillin-binding proteins, but are labile to beta-lactamases produced by other
      prevalent respiratory tract pathogens. The interactions of amoxicillin with an
      enzyme-stable cephalosporin (cefixime) with a long elimination half-life were
      examined by the checkerboard dilution method versus 39 S. pneumoniae strains (13
      resistant, 15 intermediate, and 11 susceptible to penicillin). Among 24 strains
      with evaluable drug interaction tests, 17 (71%) demonstrated partial or complete
      synergy. This favorable interaction produces a cefixime susceptibility category
      change from resistant or intermediate to susceptible for 16 of 28 strains (57%),
      when combined with < or = 1 microg/mL amoxicillin. Thus, the use of two currently
      available oral beta-lactams (amoxicillin twice a day + cefixime once a day; three
      total doses) appears to be a potential alternative treatment with greater
      spectrum for community-acquired respiratory tract infections pending clinical
      trial results.

PMID- 9635913
TI  - Bacterial resistance: a worldwide problem.
AB  - The therapeutic crisis produced by emerging antimicrobial resistances has
      compromised the chemotherapy of hospitalized patients with serious infections.
      For the most prevalent resistance problems, meropenem, a new carbapenem, appears
      to provide a potency and spectrum for: 1) extended-spectrum beta-lactamase
      producing Enterobacteriaceae; 2) Bush-Jacoby-Merdeiros group 1 enzyme-producing
      ceftazidime-resistant Enterobacter spp., Citrobacter freundii, and some Serratia
      spp.; 3) ceftazidime- and imipenem-resistant Pseudomonas aeruginosa; and 4) some
      Streptococcus spp. with elevated penicillin MICs. Documented in vitro study
      results using 1997 gram-negative blood stream infection isolates indicate a wider
      spectrum and a two- to fourfold greater potency for meropenem compared with
      imipenem. This was especially true for P. aeruginosa where 93.4% of strains were
      susceptible to meropenem (84.1% for imipenem). Also among over 30,000 reported in
      vitro meropenem results from the United States and Europe, 90.6% of gram-positive
      cocci and 99.1% of anaerobes were inhibited at < or = 4 microg/ml. Over 90% of
      ceftazidime-resistant blood stream infection strains were meropenem susceptible,
      a rate greater than those of imipenem, ciprofloxacin, and gentamicin. As the
      clinical utility of many contemporary antimicrobial agents is challenged by
      emerging resistance, the carbapenems (meropenem, imipenem) appear positioned for
      a greater role in the treatment of infections in hospitalized patients.

PMID- 9635914
TI  - Clinical strategies for serious infection: a North American perspective.
AB  - In the United States, as in Europe, clinical strategies for serious infection are
      being increasingly driven by growing numbers of cephalosporin-resistant and
      multiresistant gram-negative bacilli. In a survey of nearly 400 hospital
      intensive care units in North America, resistance rates of Klebsiella to third
      generation cephalosporins increased (from 3.6 to 14.4%) between 1990 and 1993.
      Resistance rates in Enterobacter are even higher, approaching 40%. Much of this
      resistance, which is due mainly to production of type-1 and extended spectrum
      beta-lactamases, appears to have arisen through overuse of third-generation
      cephalosporins and from poor hand-washing practices. In some American cities, a
      major reservoir of resistant organisms are nursing homes, where there is evidence
      of overuse of oral antibiotics. Currently, the most reliable agents available for
      the treatment of resistant gram-negative pathogens are the carbapenems,
      imipenem/cilastatin and meropenem, and the aminoglycoside, amikacin. A recent
      clinical study of meropenem monotherapy in patients with nosocomial pneumonia
      showed statistically significantly better clinical and microbiologic outcome
      compared with a standard regimen of ceftazidime plus tobramycin. The enhanced in
      vitro activity of meropenem against a number of key organisms may have been
      responsible for the superior results. Although the newer cephalosporins, cefepime
      and cefpirome, show greater stability to chromosomal type-1 beta-lactamases than
      ceftazidime, they have variable activity against extended spectrum beta-lactamase
      producers and can be rendered ineffective by permeability changes which occur in
      certain organisms. Carbapenems, on the other hand, possess good activity against
      virtually all of the pathogens which produce the clinically important beta
      lactamases, and represent a reliable option for treatment.

PMID- 9635915
TI  - Clinical strategies for serious infection: a European perspective.
AB  - Antimicrobial resistance in nosocomial isolates is of increasing concern to the
      clinician, particularly in intensive care units. With more expensive drugs and
      prolonged periods of hospitalization required, resistance can result in increased
      healthcare costs. For the patient, infection with multiply resistant strains of
      bacteria is associated with high mortality rates. This review focuses on the
      prevalence of nosocomial infections throughout Europe, with particular emphasis
      on the prevalence of resistance to common antimicrobial agents. The beta-lactams
      are the most frequently prescribed antimicrobials, and the growing importance of
      extended spectrum beta-lactamases and the hyperproduction of chromosomal beta
      lactamase by stably derepressed mutants in the development of microbial
      resistance are discussed. Given that the most common reason for modification of
      an initial empiric antibiotic treatment is the isolation of microorganisms not
      susceptible to the initial choice of treatment, the results from two European
      multicenter trials comparing the efficacy of the carbapenems, meropenem, and
      imipenem/cilastatin, for the treatment of serious nosocomial infections, are
      appraised. In light of these results, it can be concluded that the carbapenems
      are effective as initial empiric monotherapy for nosocomial infections because of
      their broad spectrum of efficacy and stability to beta-lactamases.

PMID- 9635916
TI  - Selecting therapy for serious infections in children: maximizing safety and
      efficacy.
AB  - Serious infections in children represent unique challenges for the treating
      physician. For the pediatric patient, considerations of drug toxicity are
      especially critical to avoid potential long-term complications of therapy. There
      are several advantages associated with using single, broad-spectrum, empiric
      antibiotic therapy, including reduced potential for drug-mediated toxicity or
      drug interactions and facilitation of home therapy. Of the antibiotics available
      for monotherapy, the carbapenems have the broadest spectrum of activity. However,
      a major obstacle toward the use of the carbapenems in pediatrics has been the
      risk of seizures occurring during therapy with imipenem/cilastatin. In clinical
      studies of meningitis and other infections in children, no drug-related seizures
      were reported when treated with the carbapenem meropenem. Meropenem monotherapy
      has been shown to be similar to ceftriaxone- and cefotaxime-based single or
      multiple antibiotic regimens, in terms of clinical and microbiologic efficacy and
      tolerability. Thus, meropenem represents a favorable treatment choice for the
      seriously ill child, either as empiric monotherapy or as definitive therapy of
      polymicrobial or nosocomial infections.

PMID- 9635917
TI  - Expanding the options for risk-based therapy in febrile neutropenia.
AB  - Fever in neutropenic cancer patients is often due to the development of an
      infection. The standard management of febrile neutropenic patients involves the
      administration of empiric, hospital-based, parenteral antibiotic therapy.
      Although this treatment strategy has evolved from experience in high-risk
      patients with hematological malignancies, in whom bacterial infection can result
      in substantial morbidity and mortality, it has been adopted for all patients with
      febrile neutropenia, largely because of the inability of clinicians to reliably
      distinguish between patients who are at high risk for developing such
      morbidity/mortality and those who are not. The development of risk-assessment
      models has facilitated the recognition of high-, moderate-, and low-risk
      subgroups among febrile neutropenic patients and allows the administration of
      outpatient antibiotic therapy to the moderate- and low-risk groups, with the same
      degree of efficacy and safety as hospital-based therapy. Monotherapy with the
      carbapenems (imipenem/cilastatin and meropenem), with their broad spectrum of
      activity and established efficacy in high-risk patients, represents realistic
      options for risk-based treatment of febrile neutropenic patients within and
      outside the hospital setting.

PMID- 9635918
TI  - Oral idarubicin and cyclophosphamide for metastatic breast cancer in elderly
      patients.
AB  - The authors treated 39 heavily pretreated breast cancer patients, median age 72,
      with a combined oral regimen featuring idarubicin and cyclophosphamide,
      administered without hospitalization in cycles repeated every 4 weeks for a total
      not to exceed idarubicin 400 mg/m2. Treatment was remarkably well tolerated, with
      generally mild hematological toxicity and only one discontinuation caused by
      severe neutropenia; non-hematologic toxicity consisted mainly of moderate nausea
      and vomiting in fewer than half the cycles, and hair loss of various severity in
      the majority of patients. Therapeutic results were graded as partial responses
      (13 cases), no change (NC; 11 cases) or progressive disease (11 cases) for a
      response rate of 37.2% (95% CI: 21.1-53.1%). The authors single out the NC issue
      as being of special interest, its mere occurrence being rewarding in the
      circumstance and its duration in excess of 5 months (seen in six cases) almost
      equivalent to therapeutic success.

PMID- 9635919
TI  - Oxaliplatin combined to 5-fluorouracil and folinic acid: an effective therapy in
      patients with advanced colorectal cancer.
AB  - Patients with colorectal carcinoma progressing after a 5-fluorouracil (5-FU)
      containing regimen were eligible. One treatment cycle consisted of repeated
      administrations of 5-FU combined to folinic acid for six times and to oxaliplatin
      for three times over 50 days. 5-FU was given at the dose of 2.6 g/m2 as a
      continuous infusion over 24 h on days 1, 8, 22, 29 and 43 preceded by i.v.
      folinic acid (FA) at a dose of 500 mg/m2 over 1 h. Oxaliplatin was given 1 h
      after 5-FU at the dose of 130 mg/m2 over a 2 h infusion on days 1, 22 and 43. A
      total of 37 patients were treated according to this schedule. The rates of
      objective responses after the first and second treatment cycles were 28 and 17%,
      respectively, with rates of tumor growth control, i.e. including the
      stabilizations, of 55 and 28%. The median duration of response was 10 months and
      the median duration of stabilizations was 6 months. The median survival time from
      initiation of oxaliplatin-containing therapy is 10 months (2-28+). The median
      survival time from the diagnosis of metastatic disease is 24 months (2-40+). The
      main toxicities were leucopenia, diarrhea, fatigue and paresthesias. The
      combination of 5-FU/FA/oxaliplatin was well tolerated and appears as a meaningful
      therapy after failure of a previous 5-FU-containing treatment.

PMID- 9635920
TI  - Phase II study of paclitaxel in pretreated advanced gastric cancer.
AB  - Patients with advanced gastric cancer unresponsive or progressing after PELF
      chemotherapy (5-fluorouracil, leucovorin, cisplatin and epidoxorubicin) received
      paclitaxel at the dose of 225 mg/m2 every 3 weeks, over 3 h infusion. Thirty-six
      patients entered the study, and all of them were evaluable for response and
      toxicity. Toxicity was mild: apart from alopecia, grade 3 toxicities were
      leukopenia and thrombocytopenia in six patients, and grade 2 neurotoxicity in
      seven patients. Eight patients (22.2%, 95% CI: 9-35%) achieved an objective
      response, with a median duration of 5 months. Median survival time for all
      patients was 8 months. In 16 of 36 patients (44%), treatment determined a
      significant relief of symptoms. Out-patient paclitaxel given over 3 h may be
      effective as salvage treatment in patients with advanced gastric cancer
      refractory to first line chemotherapy.

PMID- 9635921
TI  - Elevated expression of S100P, CAPL and MAGE 3 in doxorubicin-resistant cell
      lines: comparison of mRNA differential display reverse transcription-polymerase
      chain reaction and subtractive suppressive hybridization for the analysis of
      differential gene expression.
AB  - Subtractive suppressive hybridization (SSH) and mRNA differential display reverse
      transcription-polymerase chain reaction (DDRT-PCR) were compared for their
      ability to detect the expression of drug-resistance associated genes in a
      doxorubicin-resistant and -sensitive colon carcinoma cell line (LoVo H67P). The
      expression pattern of more than 9000 bands obtained by DDRT-PCR were identical in
      both cell lines by more than 95%. Of the remaining differentially expressed DDRT
      PCR products, 21 cDNA fragments were further analyzed after cloning. A total of
      210 clones were sequenced resulting in 40 different sequences of which only five
      were differentially expressed as revealed by Northern blot analysis. SSH, on the
      other hand, resulted in 30 different sequences of 37 clones analyzed. Thirteen of
      30 sequences (43%) could be identified by databank analysis (excluding expressed
      sequence tags) in contrast to nine of 40 clones (23%) obtained by DDRT-PCR. Of
      the clones identified by SSH, 60% exhibited a differential expression comparing
      the doxorubicin-resistant and -sensitive cell line, respectively, as compared to
      only 13% of the DDRT-PCR derived clones. The application of SSH resulted in the
      identification of differentially expressed genes in three doxorubin-resistant
      cell lines (LoVo DxR, ARH D60 and KB-V1) as compared to the sensitive parental
      cell lines. A significant higher expression of S100P, a protein involved in
      calcium metabolism, as well as MAGE 3 (melanoma antigen gene) was found in the
      resistant cell lines using this methodology. The expression of CAPL, a second
      protein involved in calcium metabolism, was only moderately elevated in the
      doxorubicin-resistant cells. We found that subtractive suppressive hybridization
      proved to be a more rapid and reliable method for the detection of differentially
      expressed mRNAs in our system.

PMID- 9635922
TI  - Enhancement of cytotoxicity by electropermeabilization: an improved method for
      screening drugs.
AB  - Electropermeabilization (EPN), also termed electroporation, is a physical method
      to overcome the barrier of the cell membrane by applying short and intense
      electric pulses. It is the basis for a new cancer treatment modality,
      electrochemotherapy, where uptake of chemotherapeutics is enhanced by EPN.
      Preclinical and clinical trials have shown that application of electric pulses in
      vivo is feasible and that electrochemotherapy is highly efficient. The aim of
      this study was to develop an improved method of screening drugs on
      electropermeabilized versus non-electropermeabilized cells. In this study we
      describe an easy protocol which gives high cell viability, good reproducibility
      and a high rate of cell permeabilization. Cell cytotoxicity is simply determined
      by the MTT assay. Cell death due to the EPN procedure was less than 4% and more
      than 90% of cells were permeabilized. For daunorubicin, doxorubicin, etoposide
      and paclitaxel, no effect of EPN was found. For carboplatin and cisplatin the
      effect of EPN was a factor 3 and 2.3, respectively, on the IC50 (inhibitory
      concentration 50%). For bleomycin we found a dramatic effect of EPN of the
      magnitude of a factor 300 on the IC50. In conclusion, we have established a new,
      easy and reliable protocol to test new drugs for cytotoxicity with or without the
      limitations of the cell membrane. Our data support the role of bleomycin as the
      drug of choice for electrochemotherapy.

PMID- 9635923
TI  - Antiproliferative effects of recombinant human bone morphogenetic protein-2 on
      human tumor colony-forming units.
AB  - Bone morphogenetic protein-2 (BMP-2) is a differentiation factor for normal
      osteoblasts. BMP-2 is structurally related to transforming growth factor-beta
      which inhibits cell proliferation and enhances apoptosis. A recent study has
      shown the presence of BMP-2 receptors on several cancer cell lines. In this
      study, we attempted to determine if recombinant human BMP-2 (rhBMP-2) can
      modulate the proliferation of human tumor colony-forming units taken from 113
      patients. Tumor cells were cultured in soft agar and continuously exposed to
      three concentrations of rhBMP-2 (10, 100 and 1000 ng/ml) for 14 days in the
      capillary cloning system. There were 65 evaluable specimens, including 17 breast
      cancers, 15 ovarian cancers, 14 non-small cell lung cancers and five prostate
      cancers. Importantly, rhBMP-2 did not stimulate the tumor cell proliferation. A
      significant inhibition (50% or less survival of tumor colony-forming units) was
      seen in 16 of 65 specimens (24.6%) at 1000 ng/ml, including five of 14 non-small
      cell lung cancers, five of 17 breast tumors and two of 15 ovarian tumors. A
      concentration-response relationship was observed (p<0.001 by Mantel-extension
      test). The results of this study encourage further evaluation of the
      antiproliferative effects of rhBMP-2 against human cancers.

PMID- 9635924
TI  - Murine peritoneal macrophages treated with cisplatin and interferon-gamma undergo
      NO-mediated apoptosis via activation of an endonuclease.
AB  - We investigated whether murine peritoneal macrophages treated with cisplatin or
      interferon (IFN)-gamma alone, or in combination, could undergo apoptosis, and
      whether this results either from the cytotoxic effect of the activating agents or
      indirectly in an autocrine manner by the cytotoxic molecules released by them
      upon activation. Our data suggest that cisplatin, which has been shown to induce
      apoptosis in a number of normal as well as tumor cell types, did not induce
      apoptosis in murine peritoneal macrophages nor was apoptosis caused by IFN-gamma.
      However, combined treatment with cisplatin and IFN-gamma induced apoptosis in
      macrophages as studied by percent DNA fragmentation assay, qualitative analysis
      of DNA on agarose gel electrophoresis, and morphological and nuclear alterations
      studied by phase contrast and fluorescence microscopy. The factor responsible for
      inducing apoptosis in macrophages was found to be a higher concentration of NO
      produced by them upon activation with cisplatin and IFN-gamma. Macrophages
      treated with cisplatin or IFN-gamma alone produced a low level of NO and did not
      undergo apoptosis. The inhibitor of NO synthase, L-NMMA, prevented apoptosis in
      macrophages treated with cisplatin and IFN-gamma, suggesting the involvement of
      NO in the induction of apoptosis in macrophages. The role of NO in inducing
      apoptosis in macrophages was further confirmed by the observation that direct
      treatment with sodium nitroprusside, a NO donor, resulted in apoptosis in
      macrophages. We have also shown that NO-induced apoptosis in macrophages
      activated with cisplatin and IFN-gamma requires activation of an endonuclease, as
      the endonuclease inhibitor, aurine tricarboxylic acid, prevented apoptosis in
      them.

PMID- 9635925
TI  - Combination therapy of active hexose correlated compound plus UFT significantly
      reduces the metastasis of rat mammary adenocarcinoma.
AB  - Synergistic effects of active hexose correlated compound (AHCC) extracted from
      mushroom on the treatment with UFT against mammary adenocarcinoma, SST-2 cells,
      in congenitally T cell-depressed spontaneously hypertensive rats (SHR) were
      observed. AHCC plus UFT had slight but significant effects on the growth of
      primary tumors. Pulmonary metastases were not inhibited by the treatment with
      AHCC plus UFT, whereas metastases to axillary lymph nodes (LN) were obviously
      inhibited. Combination of AHCC plus UFT showed similar synergistic anti
      metastatic effects in SHR rats with accelerated pulmonary metastases following
      the surgical removal of the primary tumors. In vitro studies demonstrated that
      AHCC plus UFT enhanced the NK cell activity in tumor-bearing rats, whereas UFT
      alone depressed the NK cell activity. AHCC plus UFT also enhanced the NO
      production and cytotoxicity of peritoneal macrophages. In addition, AHCC restored
      the suppressed mRNA expression of interleukin-1alpha and tumor necrosis factor
      alpha induced by the chemotherapy. Taken together, the combination of AHCC plus
      UFT brought about good therapeutic effects not only on primary tumor growth but
      also on reducing metastasis and these effects were mediated by host immunity
      which was restored or activated by AHCC. AHCC may be a good candidate for a
      biological response modifier.

PMID- 9635926
TI  - Additive effects of medroxyprogesterone acetate and 5-fluorouracil derivative on
      7,12-dimethylbenz[a]anthracene-induced rat mammary tumors.
AB  - Chronic oral administration of 1-(2-tetrahydrofuryl)-5-fluorouracil in
      combination with uracil suppressed thymidylate synthetase (TS) gene expression
      followed by reduction of TS activity in rat mammary tumors induced with 7,12
      dimethylbenz[a]anthracene. Addition of medroxyprogesterone acetate (MPA) to the
      anticancer drug caused an additional decrease in TS and thymidine kinase
      activities in the tumor growth and restoration of bone loss. These results
      suggest that the simultaneous administration of MPA and anticancer drugs causes
      increased inhibition of mammary tumor growth and also diminishes the bone loss.

PMID- 9635927
TI  - Paclitaxel plus ifosfamide in advanced ovarian cancer: results of a phase I
      study.
AB  - Patients with advanced ovarian carcinoma and an inadequate response to first-line
      platinum-based combination chemotherapy (CTX) have a very poor prognosis and
      effective salvage regimens are clearly needed. This phase I study was performed
      in order to determine the maximum tolerable dose (MTD) and dose-limiting toxicity
      (DLT) of the combination paclitaxel (P) and ifosfamide (IFO). After
      premedication, patients received P as a 3 h i.v. infusion on day 1; IFO was given
      as 1 h i.v. infusion with the standard dose of mesna i.v. on days 2-5, q day 22.
      The following dose levels (dl) were investigated: (mg/m2/day) dl1, P 135/IFO
      1500; dl2, P 135/IFO 2000; dl3, P 175/IFO 2000; and dl4, P 175/ IFO 1500.
      Eighteen patients with advanced ovarian cancer entered this trial. In eight
      patients treated with an IFO dose of 2000 mg/m2 during dl2 and 3, two required
      treatment interruptions because of CNS toxicity CTC grade 3 and one patient
      experienced nephrotoxicity CTC grade 3, Therefore the MTD of IFO used in
      combination with P and given over 4 days is reached with 2000 mg/m2/day. In the
      fourth dl we escalated the P dose up to 175 mg/m2, reduced the IFO dose to 1500
      mg/m2 and treated an additional five patients. No DLT occurred at that dl.
      Objective responses were observed at all dls. The combination of P and IFO is
      feasible and active in pretreated advanced ovarian carcinoma. dl4 is the
      recommended dose for phase II trials.

PMID- 9635928
TI  - A pilot study of fiberscopy-guided local injection of anti-cancer drugs bound to
      carbon particles for control of rectal cancer.
AB  - Rectal cancer patients with contra-indicatory risks may not be able to undergo
      surgery. In these cases the preferred treatment is chemotherapy. The present
      dosage formulation, consisting of an anti-cancer drug bound to activated carbon
      particles, was designed to deliver the anti-cancer drug at high concentration
      selectively to the injection site as well as to the regional lymph nodes and to
      improve survival of mice bearing cancer with nodal metastases, as compared to the
      same dose of aqueous anti-cancer drug in animal experiments. The present clinical
      trial includes two patients with histologically confirmed adenocarcinoma of the
      rectum and who had risks contra-indicating surgery. Carbon particles adsorbing
      anti-cancer drugs totaling 400 mg of methotrexate and 32 mg of mitomycin C in one
      patient and 100 mg of methotrexate and 8 mg of mitomycin C in another patient
      were injected into the cancer tissue under guidance of a colono-fiberscope. The
      rectal cancers were successfully reduced in size and controlled over 2 years or 6
      months until the patients died from other causes. Side effect was mild. Local
      injection of this dosage formulation will be useful for the control of rectal
      cancer in patients who cannot undergo surgery.

PMID- 9635929
TI  - Air pollution and asthma--fact or artifact? A plea for inclusion of objective
      measures in environmental epidemiology.

PMID- 9635930
TI  - Respiratory symptoms of primary school children living in a petrochemical
      polluted area in Taiwan.
AB  - In 1994-1995 a cross-sectional epidemiological study investigating the
      respiratory health of school children in two Taiwan areas was conducted; one area
      was located in a region with petrochemical manufacturing complexes (Linyuan), and
      the other was situated in a reference area with no local industrial emissions
      (Taihsi). All primary school children residing in the two areas were involved in
      the study. Four hundred seventy children were studied in the area with high
      exposure to industrial emissions, and 611 children lived in the reference area.
      Respiratory health was assessed by evaluation of the children's respiratory
      symptoms and illnesses, using a parent-completed questionnaire. Particulates,
      sulfur dioxide (SO2), nitrogen dioxide (NO2), and acid aerosols levels were
      significantly higher in the exposed area than in the reference area. The school
      children in the petrochemical area had significantly more upper respiratory
      symptoms and asthma compared with the children living in the control area.
      Although the association with known petrochemical air pollution is suggestive,
      this cross-sectional study cannot confirm a causal relation and further studies
      are needed.

PMID- 9635931
TI  - Stenotrophomonas maltophilia in cystic fibrosis: incidence and prevalence.
AB  - Stenotrophomonas maltophilia (SM) was recovered from 211 of 773 cystic fibrosis
      (CF) patients followed for at least one year, and seen between 1982 and 1994.
      Yearly prevalence (5.6% to 8.7%) and incidence rates (1.6% to 5.7%) showed no
      trends. SM persistence varied greatly and was unlike that of Pseudomonas
      aeruginosa. Fifty percent of SM-positive patients had only one positive culture
      and only 24 (11%) remained chronically infected. Although SM-positive patients
      were more likely to be hospitalized than SM-negative patients, for 55% of SM
      positive patients, acquisition did not appear to follow hospitalization. Of 40 SM
      positive patients who had a CF sibling, only 10 siblings were ever culture
      positive. When stratified by FEV1, the two-year survival for SM-positive with
      mild/moderate disease (98%) and severe disease (78%) was similar to that of our
      SM-negative patients. Five-year survival was only 40% for SM-positive patients
      with initially severe pulmonary status, compared with 72% for the SM-negative
      patients. Seventy percent of the original SM isolates were panresistant
      (susceptible to no more than one antimicrobial agent). Ten years later,
      panresistance was 84%. Despite our reassuring experience with SM, including lack
      of sibling concordance, the fact that the majority of our patients had no
      hospital exposure prior to acquisition, the high incidence of transient
      infection, and the seemingly unaffected two-year survival, there are insufficient
      data to definitively conclude that segregation of these patients would be
      beneficial. The increasing prevalence of multiply resistant gram-negative
      pathogens in CF patients suggests the need for continued caution with any
      panresistant pathogen.

PMID- 9635932
TI  - Parental attitudes toward infant pulmonary function testing.
AB  - Infant pulmonary function tests (PFTs) have proven increasingly popular and
      useful for clinical and research purposes. Informed consent requires accurate
      information on side effects. Our aim was to quantify minor side effects from a
      parental point of view by means of a questionnaire. The parents of 97 infants
      attending for PFTs were asked to complete a simple questionnaire. Eighty-one
      parents (84%) returned the questionnaire. Forty-one percent felt that their
      infants were not troubled by the process of administering the sedative chloral
      hydrate, whereas 55% suffered mild to moderate distress. In contrast, 94% of
      infants were not distressed by the actual PFTs. Similarly, 46% of parents were
      not distressed by the administration of sedative to their infant, with 49%
      expressing distress to a mild or moderate degree. Although 73% of parents were
      not distressed by watching their infants undergo the PFTs, 27% were to a mild to
      moderate degree. Seventy-three percent of infants were untroubled on waking.
      Seventy percent of infants had a good nights sleep after the PFTs. The vast
      majority of parents (94%) were happy to recommend that others allow their infants
      to undergo similar testing. We noted that most problems caused by infant PFTs
      relate to the administration of the sedative. Most infants awake from the tests
      not distressed and sleep normally the following night.

PMID- 9635933
TI  - Effect of salmeterol treatment on nitric oxide level in exhaled air and dose
      response to terbutaline in children with mild asthma.
AB  - The aim of this study was to investigate whether regular treatment with inhaled
      salmeterol modifies the dose-response curve to the inhaled short-acting beta2
      agonist terbutaline or affects the concentration of nitric oxide (NO) in exhaled
      air of children with asthma. Twenty-two children aged 7 to 15 years (mean = 11.6
      years) with mild asthma were treated with inhaled 50 microg salmeterol twice
      daily or placebo for 3 weeks in a randomized double-blind cross-over study. These
      treatments were followed by treatment with inhaled 200 microg budesonide twice
      daily for 3 weeks. On the last day of each period, NO level was measured in
      exhaled air and a cumulative dose-response experiment with terbutaline
      (cumulative dose: 1,475 microg) was performed. Baseline lung functions after
      salmeterol treatment were significantly higher than baseline after placebo (P +
      0.05). Salmeterol treatment flattened out the dose-response curve to terbutaline
      such that higher doses of terbutaline were required to produce the same degree of
      bronchodilation (ED50 for FEV1 was increased by an estimated factor of 70 (95%
      CI: 0.8-6307) and ED50 for FEF25-75 by a factor of 41 (95% CI: 6.7-254); P <
      0.05). NO levels were unaffected by salmeterol treatment (12.7 ppb; placebo =
      10.7 ppb), but were significantly reduced during budesonide therapy (5.2 ppb; P <
      0.001). The corresponding maximal NO levels were 19.5 (placebo), 22.9
      (salmeterol), and 9.4 ppb (budesonide). We conclude that 3 weeks treatment with
      salmeterol does not affect NO levels in exhaled air, but it significantly changes
      the dose-response curve to terbutaline.

PMID- 9635934
TI  - Specific airway resistance, interrupter resistance, and respiratory impedance in
      healthy children aged 2-7 years.
AB  - We report data on respiratory function in healthy children aged 2-7 years in whom
      we measured respiratory resistance by the interrupter technique (Rint); total
      respiratory impedance (Zrs), respiratory resistance (Rrs), and reactance (Xrs) by
      the impulse oscillation technique; and specific airway resistance (sRaw) by a
      modified procedure method in the whole body plethysmograph. Measurements were
      attempted in 151 children and were successfully obtained in 121 children with a
      mean (SD) age of 5.3 (1.5) years; no measurements were possible in 30 children
      (mean age 3 (0.9) years). The repeatability of measurements was independent of
      the age of the subjects, and the within-subject coefficient of variation was
      11.1%, 8.1%, 10.8%, and 10.2% for sRaw, Rint, Zrs, and Rrs at 5 Hz (Rrs5),
      respectively. All lung function indices were linearly related to age, height, and
      weight. A significant negative correlation with age, height, and weight was found
      for Rint, Zrs, and Rrs5. Xrs5 was positively correlated to age and body size. The
      mean values of Rint, Rrs5, Xrs5, and Zrs in children younger and older than 5
      years were 1.04, 1.38, -0.5, and 1.48 kPa x L(-1) x s and 0.9, 1.18, -0.37, and
      1.23 kPa x L(-1) x s, respectively. sRaw showed no significant correlation with
      body size or age and the mean sRaw in children younger and older than 5 years was
      1.09 and 1.13 kPa x s, respectively. None of the indices of respiratory function
      differed between boys and girls. Xrs and Rrs exhibited a significant frequency
      dependence in the range of 5-35 Hz. The techniques applied in this study require
      minimal cooperation and allow measurement of lung function in 80% of our
      population of awake young children. Further studies are needed to evaluate the
      potentials of the presently established reference values for clinical and
      epidemiological purposes.

PMID- 9635935
TI  - Environmental effects on pulmonary mechanics and the response to inhaled
      methacholine.
AB  - To investigate the role of environmental exposure from birth on airway and lung
      parenchymal responsiveness to inhaled methacholine (Mch), three litters of
      puppies (n = 14) were studied when 8-10 weeks of age. Two litters, one mongrel (n
      = 7) and one foxhound-beagle cross (n = 3), were born and raised in a clean
      animal house environment (clean mongrels and clean cross, respectively). Another
      litter of mongrels was born (n = 4) and raised in an external environment
      (external mongrels), exposed to normal rural environmental contaminants. Animals
      were studied open-chested with alveolar capsules used to partition mechanics into
      airway and parenchymal components. Lung mechanics were measured after abrupt flow
      interruptions. The animals born and raised in the external environment were
      significantly more responsive to inhaled Mch than those born and raised in the
      clean environment. This finding was true for both airway and parenchymal
      responsiveness. The group mean effective dose of Mch that produced a doubling of
      airway resistance (ED200Raw) for the external mongrel group was 4.40 mg/ml
      compared with 19.44 mg/ml for the clean mongrel group and 16.34 mg/ml for the
      clean cross group (P < 0.02). The group mean effective dose of Mch that produced
      a doubling of pressure difference in airways after the initial rapid rise in
      airway pressure (ED200Pdif) for the external mongrel group was 0.79 mg/ml
      compared with 3.90 mg/ml for the clean mongrel group and 10.78 mg/ml for the
      clean cross group (P < 0.01). Generalized linear modeling analysis showed that
      both "environment" and "breed" were significant factors in determining ED200Pdif,
      but only "environment" significantly influenced ED200Raw. In summary, the present
      study has demonstrated that the environment in which an animal is born and raised
      can influence lung mechanics and responsiveness to methacholine. This finding is
      particularly true for the lung parenchyma.

PMID- 9635936
TI  - Transcutaneous oxygen tension measurements during methacholine challenge of
      prematurity in infants with chronic lung disease.
AB  - Chronic lung disease (CLD) of prematurity may be caused by a number of insults
      during mechanical ventilation, including barotrauma and hyperoxia. To evaluate
      bronchial hyperresponsiveness (BHR) in infants with CLD of prematurity, we
      measured changes in transcutaneous oxygen tensions (tcPO2) during methacholine
      inhalation challenge. Twelve infants with CLD and 22 age-matched children without
      respiratory diseases were enrolled in this study (ages--5 to 36 months; mean age-
      16.2 months). Serial doses of methacholine were doubled until a 10% decrease in
      tcPO2 from baseline was reached. The cumulative dose of methacholine inhaled by
      the time tcPO2 had been reached (Dmin-PO2) was considered to represent the dose
      at which reactivity to methacholine (RO2meth) had occurred. In the CLD group,
      Dmin-PO2 (3.50 +/- 0.1 log x milli-units) was significantly lower than in the
      preterm control infant group (4.31 +/- 0.2 log x milli-units) and the term infant
      group (4.21 +/- 0.1 log x milli-units) (P = 0.004, P < 0.001). Dmin-PO2 in the
      preterm control infant group was not significantly different than in the term
      infant group (P > 0.5). These results suggest that infants who require additional
      therapeutic oxygen and mechanical ventilation during the early months of life are
      at risk of developing early-onset, long-lasting respiratory disease that is
      related to an acquired BHR.

PMID- 9635937
TI  - Hypoxemia due to the obstruction of a right tracheal bronchus by an endotracheal
      tube in a child with left bronchial foreign body aspiration.

PMID- 9635938
TI  - Fatal desquamative interstitial pneumonia associated with proven CMV infection in
      an 8-month-old boy.

PMID- 9635939
TI  - Braided bronchus: a previously undescribed airway anomaly.
AB  - Infants with congenital heart disease frequently experience recurrent
      atelectasis, in many cases associated with anomalous branching of the bronchial
      tree. The bridging bronchus has been well described and has been associated with
      both left-sided obstructive lesions and a sling-like left pulmonary artery. We
      describe a similar, though distinct airway anomaly, the "braided bronchus,"
      associated with a bridging bronchus in a child with coarctation of the aorta and
      recurrent atelectasis. Methods used to delineate the "braided bronchus" are
      described.

PMID- 9635940
TI  - Nuclear rumblings in the East.

PMID- 9635941
TI  - J-curve not burned off by HOT study. Hypertension Optimal Treatment.

PMID- 9635942
TI  - Transplant tolerance: will genes protect the graft?

PMID- 9635943
TI  - Prediction of recovery from post-traumatic vegetative state.

PMID- 9635945
TI  - How many neutrophils are enough?

PMID- 9635944
TI  - Patients' records on the Internet: a boost for evidence-based medicine.

PMID- 9635946
TI  - Improved prognosis for biomarkers in breast cancer.

PMID- 9635947
TI  - Effects of intensive blood-pressure lowering and low-dose aspirin in patients
      with hypertension: principal results of the Hypertension Optimal Treatment (HOT)
      randomised trial. HOT Study Group.
AB  - BACKGROUND: Despite treatment, there is often a higher incidence of
      cardiovascular complications in patients with hypertension than in normotensive
      individuals. Inadequate reduction of their blood pressure is a likely cause, but
      the optimum target blood pressure is not known. The impact of acetylsalicylic
      acid (aspirin) has never been investigated in patients with hypertension. We
      aimed to assess the optimum target diastolic blood pressure and the potential
      benefit of a low dose of acetylsalicylic acid in the treatment of hypertension.
      METHODS: 18790 patients, from 26 countries, aged 50-80 years (mean 61.5 years)
      with hypertension and diastolic blood pressure between 100 mm Hg and 115 mm Hg
      (mean 105 mm Hg) were randomly assigned a target diastolic blood pressure. 6264
      patients were allocated to the target pressure < or =90 mm Hg, 6264 to < or =85
      mm Hg, and 6262 to < or =80 mm Hg. Felodipine was given as baseline therapy with
      the addition of other agents, according to a five-step regimen. In addition, 9399
      patients were randomly assigned 75 mg/day acetylsalicylic acid (Bamycor, Astra)
      and 9391 patients were assigned placebo. FINDINGS: Diastolic blood pressure was
      reduced by 20.3 mm Hg, 22.3 mm Hg, and 24.3 mm Hg, in the < or =90 mm Hg, < or
      =85 mm Hg, and < or =80 mm Hg target groups, respectively. The lowest incidence
      of major cardiovascular events occurred at a mean achieved diastolic blood
      pressure of 82.6 mm Hg; the lowest risk of cardiovascular mortality occurred at
      86.5 mm Hg. Further reduction below these blood pressures was safe. In patients
      with diabetes mellitus there was a 51% reduction in major cardiovascular events
      in target group < or =80 mm Hg compared with target group < or =90 mm Hg (p for
      trend=0.005). Acetylsalicylic acid reduced major cardiovascular events by 15%
      (p=0.03) and all myocardial infarction by 36% (p=0.002), with no effect on
      stroke. There were seven fatal bleeds in the acetylsalicylic acid group and eight
      in the placebo group, and 129 versus 70 non-fatal major bleeds in the two groups,
      respectively (p<0.001). INTERPRETATION: Intensive lowering of blood pressure in
      patients with hypertension was associated with a low rate of cardiovascular
      events. The HOT Study shows the benefits of lowering the diastolic blood pressure
      down to 82.6 mm Hg. Acetylsalicylic acid significantly reduced major
      cardiovascular events with the greatest benefit seen in all myocardial
      infarction. There was no effect on the incidence of stroke or fatal bleeds, but
      non-fatal major bleeds were twice as common.

PMID- 9635948
TI  - Prediction of recovery from post-traumatic vegetative state with cerebral
      magnetic-resonance imaging.
AB  - BACKGROUND: The early post-traumatic vegetative state (VS) is compatible with
      recovery. Various clinical and laboratory tests have failed to predict recovery
      so we assessed the value of cerebral magnetic-resonance imaging (MRI) in
      prediction of recovery. METHODS: 80 adult patients in post-traumatic VS had
      cerebral MRI between 6 weeks and 8 weeks after injury. MRIs were reviewed by
      three neuroradiologists for the number, sizes, and location of brain lesions.
      Three neurologists assessed the patients at the time of MRI and at 2 months, 3
      months, 6 months, 9 months, and 12 months after injury using the Glasgow Outcome
      Scale. FINDINGS: At 12 months, 38 patients had recovered while 42 patients
      remained in the VS. The demographic characteristics and causes and severity of
      injury were similar in patients in persistent VS (PVS) and those who recovered
      (NPVS). An average of 6.1 different brain areas were injured in patients in PVS
      compared with 4.6 areas in patients who had NPVS. Patients in PVS revealed a
      significantly higher frequency of corpus callosum, corona radiata, and
      dorsolateral brainstem injuries than did patients who recovered. Logistic
      regression analysis showed that corpus callosum and dorsolateral brainstem
      injuries were predictive of non-recovery. The adjusted odds ratios for non
      recovery of patients with a corpus callosum lesion and dorsolateral brainstem
      injury were 213.8 (95% CI 14.2-3213.3), and 6.9 (11-42.9), respectively. In
      contrast, clinical characteristics, such as initial score on the Glasgow Coma
      Scale, age, and pupillary abnormalities failed to predict recovery.
      INTERPRETATION: Cerebral MRI findings in the subacute stage after head injury can
      predict the outcome of the post-traumatic VS. Corpus callosum and dorsolateral
      brainstem lesions are highly significant in predicting non-recovery.

PMID- 9635949
TI  - Low plasma concentrations of interleukin 10 in severe malarial anaemia compared
      with cerebral and uncomplicated malaria.
AB  - BACKGROUND: Severe anaemia is a major complication of malaria but little is known
      about its pathogenesis. Experimental models have implicated tumour necrosis
      factor (TNF) in induction of bone-marrow suppression and eythrophagocytosis.
      Conversely, interleukin 10 (IL-10), which mediates feed-back regulation of TNF,
      stimulates bone-marrow function in vitro and counteracts anaemia in mice. We
      investigated the associations of these cytokines with malarial anaemia. METHODS:
      We enrolled 175 African children with malaria into two studies in 1995 and 1996.
      In the first study, children were classified as having severe anaemia (n=10),
      uncomplicated malaria (n=26), or cerebral anaemia (n=41). In the second study,
      patients were classified as having cerebral malaria (n=33) or being fully
      conscious (n=65), and the two groups were subdivided by measured haemoglobin as
      normal (>110 g/L), moderate anaemia (60-90 g/L), and severe anaemia (<50 g/L). IL
      10 and TNF concentrations were measured by ELISA in plasma samples from all
      patients. FINDINGS: IL-10 concentrations were significantly lower in patients
      with severe anaemia than in all other groups. In 1995, geometric mean plasma IL
      10 in patients with severe anaemia was 270 pg/mL (95% CI 152-482) compared with
      725 pg/mL (465-1129) in uncomplicated malaria and 966 pg/mL (612-1526) in
      cerebral malaria (p<0.03). In 1996, fully conscious patients with severe anaemia
      also had significantly lower IL-10 concentrations than all other groups,
      including cerebral-malaria patients with severe anaemia and all patients with
      moderate anaemia (p<0.001). In both studies, TNF concentrations were
      significantly higher in cerebral malaria than in fully conscious patients
      (p<0.01). By contrast, the ratio of TNF to IL-10 was significantly higher in
      fully conscious patients with severe anaemia than in all other groups (p<0.001).
      INTERPRETATION: Our findings identify severe malarial anaemia as a distinct
      disorder in which insufficient IL-10 response to high TNF concentrations may have
      a central role.

PMID- 9635950
TI  - Irregular regeneration of hepatocytes and risk of hepatocellular carcinoma in
      chronic hepatitis and cirrhosis with hepatitis-C-virus infection.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) commonly develops in patients with
      chronic hepatitis or cirrhosis of the liver caused by hepatitis-C-virus (HCV)
      infection. We prospectively studied whether irregular regeneration of hepatocytes
      is a risk factor for HCC in these patients. METHODS: 242 patients were enrolled
      after liver biopsy and followed up by ultrasonographic scanning every 3 months.
      We examined age, sex, platelet count, the diagnosis of cirrhosis or chronic
      hepatitis, liver-cell dysplasia, and irregular regeneration. We classified
      irregular regeneration as slight or severe, based on histological expression of
      pleiomorphism, anisocytosis, bulging, and map-like distribution of hepatocytes.
      FINDINGS: 37 of 63 patients with cirrhosis and 26 of 179 with chronic hepatitis
      were judged to have severe irregular regeneration. HCC was diagnosed in 33 of 63
      patients with cirrhosis (29 had severe irregular regeneration) and 12 of 179
      patients with chronic hepatitis (11 had severe irregular regeneration) during
      mean follow-up of 5.5 years (SD 4.1; range 1-16). Multivariate analysis with a
      proportional-hazards model showed severe irregular regeneration (relative risk
      15.1 [95% CI 5.6-40.7], p<0.0001) and a diagnosis of cirrhosis (3.8 [1.7-8.2],
      p=0.0008) to be significant risk factors for HCC. Within the diagnostic
      categories, irregular regeneration was also significant (cirrhosis 6.8 [2.1
      21.9], p=0.0014; chronic hepatitis 28.5 [2.9-276.4], p=0.0038). INTERPRETATION:
      We recommend that liver biopsy to look for irregular regeneration should be done
      in patients with HCV-related chronic liver diseases. Those with severe irregular
      regeneration should be followed up carefully.

PMID- 9635951
TI  - Effect of immunosuppression after cardiac transplantation in early childhood on
      antibody response to polysaccharide antigen.
AB  - BACKGROUND: Three children who had cardiac transplantation before age 4 years
      later presented with recurrent sinopulmonary infection caused by organisms
      including Streptococcus pneumoniae, in which capsular polysaccharide plays an
      important part, one developed bronchiectasis. We therefore studied responses to
      polysaccharide antigen after immunosuppression started in early childhood.
      METHODS: Antibodies against pneumococcal and haemophilus polysaccharides, and
      total IgG, IgG1, IgG2, and IgA concentrations were measured in 33 cardiac
      transplant recipients transplanted before the age 4 years (group 1) and after
      that age (group 2). Patients with low pneumococcal and haemophilus antibody
      concentrations were immunised with 23 polyvalent pneumococcal and tetanus
      haemophilus conjugate vaccines and antibody responses were measured. FINDINGS:
      Five patients from group 1 and seven from group 2 were transplanted for
      congenital heart disease and ten patients in each group had heart transplants
      because of cardiomyopathy; none were asplenic. Group 1 (16 patients) were aged 2
      10 years when investigated, group 2 (17 patients), were 6-16 years. Four of 16
      patients in group 1 responded to pneumococcal polysaccharide vaccine compared
      with 14 of 17 in group 2 (p=0.0016). This difference remained when those in group
      1, aged less than 4 years at investigation, were excluded (p=0.0060). Response to
      haemophilus-conjugate vaccine was similar in both groups (14 of 16 vs 14 of 17,
      p=1.0). Significantly more patients who failed to respond to pneumococcal vaccine
      had low IgG2 concentrations (p=0.0269). INTERPRETATION: Children who had a
      transplantation and immunosuppression in early childhood before they had
      developed antibody responses to pneumococcal polysaccharide, still failed to show
      a response when older-ie, when such responses are the norm. Ongoing
      immunosuppression prevents the maturation of antipolysaccharide responses leaving
      children susceptible to severe and recurrent damaging infection.

PMID- 9635952
TI  - A boy with chickenpox whose fingers peeled.

PMID- 9635953
TI  - Treatment of neurotrophic keratopathy with substance-P-derived peptide (FGLM) and
      insulin-like growth factor I.

PMID- 9635954
TI  - Low-dose MDMA ("ecstasy") induces vasopressin secretion.

PMID- 9635955
TI  - 5-HT2A promoter polymorphism in anorexia nervosa.

PMID- 9635956
TI  - 5-HT2A promoter polymorphism -1438G/A, anorexia nervosa, and obsessive-compulsive
      disorder.

PMID- 9635957
TI  - Follow-up of ventricular pre-excitation in Japanese schoolchildren.

PMID- 9635958
TI  - ABO blood group and inhaled nitric oxide in acute respiratory distress syndrome.

PMID- 9635959
TI  - Association at LRP gene locus with sporadic late-onset Alzheimer's disease.

PMID- 9635960
TI  - Could lightning injury be magnetically induced?

PMID- 9635961
TI  - HIV-1-vaccine-trial go-ahead reawakens ethics debate.

PMID- 9635962
TI  - Unravelling the complexities of environmental effects on breast-cancer risk.

PMID- 9635963
TI  - The copolymer-1 story so far.

PMID- 9635964
TI  - Famine appeals versus long-term aid by the UK.

PMID- 9635966
TI  - Canada starts renewed effort against tobacco-industry advertising.

PMID- 9635968
TI  - Kidney stones.

PMID- 9635969
TI  - What do the basal ganglia do?
AB  - We propose that the basal ganglia support a basic attentional mechanism operating
      to bind input to output in the executive forebrain. Such focused attention
      provides the automatic link between voluntary effort, sensory input, and the
      calling up and operation of a sequence of motor programmes or thoughts. The
      physiological basis for this attentional mechanism may lie in the tendency of
      distributed, but related, cortical activities to synchronise in the gamma (30 to
      50 Hz) band, as occurs in the visual cortex. Coherent and synchronised elements
      are more effective when convergence occurs during successive stages of
      processing, and in this way may come together to give the one gestalt or action.
      We suggest that the basal ganglia have a major role in facilitating this aspect
      of neuronal processing in the forebrain, and that loss of this function
      contributes to parkinsonism and abulia.

PMID- 9635970
TI  - Decentralisation and privatisation of long-term care in UK and USA.

PMID- 9635971
TI  - Calcium channel blockers and cardiovascular risk in diabetes.

PMID- 9635972
TI  - Calcium channel blockers and cardiovascular risk in diabetes.

PMID- 9635973
TI  - Internet access to patients' records.

PMID- 9635974
TI  - Acellular pertussis vaccines: progress but deja vu.

PMID- 9635975
TI  - Micronutrient deficiencies and protein-energy malnutrition.

PMID- 9635976
TI  - HIV-1 transmission through artificial insemination.

PMID- 9635977
TI  - Isoniazid versus rifampicin and pyrazinamide for prevention of tuberculosis in
      HIV-1 infection.

PMID- 9635978
TI  - Increase of allergy in East Germany.

PMID- 9635979
TI  - Increase of allergy in East Germany.

PMID- 9635980
TI  - NIH follow-up study of women with augmentation mammoplasty: investigator replies.

PMID- 9635981
TI  - Gammow bag for acute mountain sickness.

PMID- 9635982
TI  - Human-milk lactadherin in protection against rotavirus.

PMID- 9635983
TI  - The viable myocardium.

PMID- 9635984
TI  - Costs of stenting for acute myocardial infarction.

PMID- 9635985
TI  - Coronary microvascular spasm and angina pectoris.

PMID- 9635986
TI  - N-methyl-(R)-salsolinol and Parkinson's disease.

PMID- 9635987
TI  - Butyrylcholinesterase K: an association with dementia with Lewy bodies.

PMID- 9635988
TI  - Harm reduction and needle exchange programmes.

PMID- 9635989
TI  - Harm reduction and needle exchange programmes.

PMID- 9635990
TI  - Water hyacinths.

PMID- 9635991
TI  - Botulinum toxin, a historical note.

PMID- 9635992
TI  - Lies, damned lies, and evidence-based medicine.

PMID- 9635993
TI  - The questionable role of saturated and polyunsaturated fatty acids in
      cardiovascular disease.
AB  - A fat diet, rich in saturated fatty acids (SFA) and low in polyunsaturated fatty
      acids (PUFA), is said to be an important cause of atherosclerosis and
      cardiovascular diseases (CVD). The evidence for this hypothesis was sought by
      reviewing studies of the direct link between dietary fats and atherosclerotic
      vascular disease in human beings. The review included ecological, dynamic
      population, cross-sectional, cohort, and case-control studies, as well as
      controlled, randomized trials of the effect of fat reduction alone. The positive
      ecological correlations between national intakes of total fat (TF) and SFA and
      cardiovascular mortality found in earlier studies were absent or negative in the
      larger, more recent studies. Secular trends of national fat consumption and
      mortality from coronary heart disease (CHD) in 18-35 countries (four studies)
      during different time periods diverged from each other as often as they
      coincided. In cross-sectional studies of CHD and atherosclerosis, one group of
      studies (Bantu people vs. Caucasians) were supportive; six groups of studies
      (West Indians vs. Americans, Japanese, and Japanese migrants vs. Americans,
      Yemenite Jews vs. Yemenite migrants; Seminole and Pima Indians vs. Americans,
      Seven Countries) gave partly supportive, partly contradictive results; in seven
      groups of studies (Navajo Indians vs. Americans; pure vegetarians vs. lacto-ovo
      vegetarians and non-vegetarians, Masai people vs. Americans, Asiatic Indians vs.
      non-Indians, north vs. south Indians, Indian migrants vs. British residents,
      Geographic Study of Atherosclerosis) the findings were contradictory. Among 21
      cohort studies of CHD including 28 cohorts, CHD patients had eaten significantly
      more SFA in three cohorts and significantly less in one cohort than had CHD-free
      individuals; in 22 cohorts no significant difference was noted. In three cohorts,
      CHD patients had eaten significantly more PUFA, in 24 cohorts no significant
      difference was noted. In three of four cohort studies of atherosclerosis, the
      vascular changes were unassociated with SFA or PUFA; in one study they were
      inversely related to TF. No significant differences in fat intake were noted in
      six case-control studies of CVD patients and CVD-free controls; and neither total
      or CHD mortality were lowered in a meta-analysis of nine controlled, randomized
      dietary trials with substantial reductions of dietary fats, in six trials
      combined with addition of PUFA. The harmful effect of dietary SFA and the
      protective effect of dietary PUFA on atherosclerosis and CVD are questioned.

PMID- 9635994
TI  - Dietary fats and heart disease--dogma challenged?

PMID- 9635995
TI  - Observational research and evidence-based medicine: What should we teach young
      physicians?

PMID- 9635996
TI  - Correlates of family history of coronary artery disease in children.
AB  - The atherosclerotic process begins in childhood but, in general, does not reach
      the clinical horizon until after the fifth decade of life, at which point the
      best opportunities for prevention and intervention have been lost. In order to
      identify children with a high risk of developing coronary artery disease (CAD),
      risk factors measured in children that are the most informative indicators of
      future risk must be identified. Using a novel analytical strategy that
      incorporates a continuum of information about context dependency, we investigated
      whether there were significant differences in intermediate biochemical and
      physiological traits between children (189 females and 188 males, ages 5-20.5
      years) with and without a strong family history of clinically-defined CAD at
      three levels of context dependency (coarse grain, medium grain, and fine grain).
      In the coarse-grained analysis we tested for differences in mean levels of nine
      intermediate traits (lipids, apolipoproteins, blood pressure traits) and indices
      of external and internal environmental context (age, body mass index, smoking
      status). Female children with a strong family history had higher average levels
      for total cholesterol, triglyceride, Apo B, and systolic blood pressure and were
      on average older and weighed more than female children with a weak family history
      of CAD. Male children with a strong family history of CAD had higher average
      levels of triglycerides and were on average older than male children with a weak
      family history. In the medium-grained analysis we investigated whether the
      regression relationships between each intermediate trait and each measure of
      environmental context was significantly different between children with and
      without a strong family history of CAD. Our results indicate that children with a
      strong family history of CAD have a significantly different relationship between
      their intermediate traits and environmental contexts than children with a weak
      family history. In the fine-grained analysis, we stratified the sample into age,
      BMI, and smoking subgroups and tested for mean differences in the intermediate
      traits between children with and without a strong family history. For seven of
      the nine intermediate traits we found evidence of significant mean differences
      between children with and without a strong family history of CAD in particular
      age and BMI subgroups in nonsmokers that were not expected given the results from
      separate age-dependent or BMI-dependent marginal analyses. From these analyses,
      we conclude that the inferences about intermediate biochemical and physiological
      trait associations with family history of CAD depend on where on the coarse-grain
      to fine-grain continuum of context dependency the analysis is performed. In many
      cases, inferences at one level of investigation are different than the inferences
      made at a coarser or finer level. This study documents the complexity of the
      associations between intermediate traits and risk of CAD and raises the question
      of how many models are needed to maximize disease prediction and where these
      models should fall on the coarse- to fine-grain continuum.

PMID- 9635997
TI  - Coffee consumption in hypertensive men in older middle-age and the risk of
      stroke: the Honolulu Heart Program.
AB  - OBJECTIVE: To examine the association between coffee consumption and the
      development of stroke in men at high risk for cardiovascular disease. METHODS:
      Coffee intake was observed from 1965 to 1968 in a cohort of men enrolled in the
      Honolulu Heart Program with follow-up for incident stroke over a 25-year period.
      Subjects were 499 hypertensive men (having systolic or diastolic blood pressures
      at or above 140 and 90 mm Hg, respectively) in older middle-age (55 to 68 years)
      when follow-up began. Past and current cigarette smokers were excluded from
      follow-up. RESULTS: In the course of follow-up, 76 men developed a stroke. After
      age-adjustment, risk of thromboembolic stroke increased significantly with
      increases in coffee consumption (P = 0.002). No relationships were observed with
      hemorrhagic stroke. When adjusted for other factors, the risk of thromboembolic
      stroke was more than doubled for men who consumed three cups of coffee per day as
      compared to nondrinkers of coffee (RR = 2.1; 95% CI = 1.2-3.7). CONCLUSIONS:
      Although in need of further confirmation, consumption of coffee appears to be
      positively associated with an increased risk of thromboembolic stroke in
      hypertensive men in older middle-age. Findings suggest that it may be prudent to
      advise older middle-aged men with hypertension who consume large amounts of
      coffee to consider reducing their coffee intake.

PMID- 9635998
TI  - Prevalence and risk factors for nosocomial lower respiratory tract infections in
      German hospitals.
AB  - The prevalence and risk factors for nosocomial lower respiratory tract infections
      (LRTI) in Germany were determined as part of a national survey on nosocomial
      infections. The study included 14,966 patients in 72 representatively selected
      hospitals with departments of general medicine, surgery, obstetrics, gynecology,
      and intensive care units (ICU). Surveillance was carried out by four previously
      validated medical doctors who strictly applied the CDC-criteria for diagnosis of
      nosocomial infections. The overall prevalence of hospital-acquired LRTI was 0.72%
      with the highest rate in hospitals with more than 600 beds (1.08%) and among the
      patients on intensive care units (9.00%). Ventilator-associated pneumonia rates
      were highest in patients on ICUs (13.27). Polytrauma, impaired consciousness,
      chronic airway disease, prior surgery, and cardiovascular disease were
      significantly related to the occurrence of nosocomial LRTI. P. aeruginosa was the
      predominant organism causing nosocomial LRTI. Nosocomial LRTI remain a problem
      mainly on ICUs. Patients at risk should be monitored with extra care.

PMID- 9635999
TI  - Comparative safety of two recombinant hepatitis B vaccines in children: data from
      the Vaccine Adverse Event Reporting System (VAERS) and Vaccine Safety Datalink
      (VSD).
AB  - BACKGROUND: Preliminary review of data from the Vaccine Adverse Event Reporting
      System (VAERS), 1991-1994, revealed that more serious adverse events were
      reported in children who received a specific brand of recombinant hepatitis B
      (HepB) vaccine. OBJECTIVE: To compare the post-marketing safety experience of the
      two recombinant HepB vaccines licensed for use in infants and children in the
      United States. DESIGN: Review of a case series derived from passive surveillance
      data in the national VAERS. A retrospective cohort study using data from one
      health maintenance organization participating in Vaccine Safety Datalink (VSD), a
      computerized record linkage system. POPULATIONS STUDIED: U.S. children, ages
      birth-10 years for whom adverse events after HepB vaccine were reported to VAERS,
      1991-1994. Children, ages birth-6 years, who received HepB vaccine at Kaiser
      Permanente Medical Care Program, Northern California, 1991-1994. MAIN OUTCOME
      MEASURES: VAERS reporting rates for each vaccine by manufacturer were calculated
      from the numbers of reported events occurring within 30 days of HepB vaccination
      and the number of doses distributed by the manufacturers. VSD event rates for
      each vaccine were calculated from the numbers of hospitalization or emergency
      room visits within 30 days of HepB vaccination and the number of vaccine doses
      administered to the cohort. RESULTS: In VAERS, higher rates of serious events
      (i.e., life threatening or resulting in hospitalization or permanent disability)
      were reported in children who received Vaccine A vs. Vaccine B (relative risk
      [RR]: 3.13-8.18, P < 0.01), particularly by those vaccinated in the private (RR:
      7.62-28.58, P < 0.01), but not public sector (RR: 2.12, P = 0.19). Similar types
      of events were reported in recipients of both vaccines. In contrast, analysis of
      VSD data showed no significant difference in rates of hospitalization or ER
      visits in children who received either HepB vaccine (RR: 0.96-1.25, P > 0.05).
      CONCLUSIONS: Our investigation reveals that it is unlikely there is a true
      difference between rates of serious events temporally associated with the two
      HepB vaccines in children. This study demonstrates the dual roles played by VAERS
      and VSD in providing a more complete picture of the post-marketing safety profile
      of childhood vaccines, and underscores the importance of using other analytic
      studies to evaluate findings from passive surveillance systems of adverse events.

PMID- 9636000
TI  - A case-control study on risk factors for Peyronie's disease.
AB  - The aim of this study was to investigate the relationship between history of
      selected diseases, genital traumas, and Peyronie's disease. A hospital-based case
      control study was conducted at the Andrologic and Surgical Outpatient Units of
      the Policlinico Gemelli, Rome, where 134 men with Peyronie's disease and 134 male
      controls were interviewed. The association between Peyronie's disease and
      selected characteristics was estimated by means of odds ratios (OR) and 95%
      confidence intervals (CI). Patients who underwent invasive procedures on the
      penis (i.e., urethral catheterization, cystoscopy, and transurethral
      prostatectomy) had a 16-fold increased risk for Peyronie's disease (OR = 16.1,
      95% CI: 1.8-142), while a nearly three-fold increase was observed among patients
      who had genital and/or perineal traumatisms (95% CI: 1.0-7.1). A history of
      urethritis, uricacidemia, and lipoma was also significantly associated with an
      increased risk for Peyronie's disease. Twenty-one percent of the cases and none
      of the controls were affected by Dupuytren's contracture, and 4% of cases and
      none of the controls reported familial history for Peyronie's disease. The
      frequency of inflammatory or fibromatous lesions of the genital tract of the
      partner was significantly higher in men with Peyronie's disease than among
      controls. These results were consistent when performing a stratified analysis
      according to the type of controls (i.e., controls affected by urologic or by
      digestive conditions) to rule out the potential effect of recall bias. The
      findings of the study lend support to clinical reports stressing the importance
      of genital traumatisms and genetic conditions in the development of Peyronie's
      disease.

PMID- 9636001
TI  - Validation of a telephone questionnaire for Parkinson's disease.
AB  - As part of a genetic study, we investigated the accuracy of a telephone
      questionnaire to diagnose or screen for Parkinson's disease (PD). We studied 20
      PD patients randomly selected among all incident cases in Olmsted County,
      Minnesota, for the period 1970 through 1988. Each patient was matched by age and
      sex to a subject free of PD or parkinsonism residing in the same county. In
      addition, we studied 20 patients with PD referred to our institution from outside
      of Olmsted County between 1991 and 1993. Medical record documentation of disease
      status for both affected and unaffected subjects served as the standard for
      comparison. A trained interviewer kept unaware of disease status administered
      nine symptom questions via telephone to all study subjects (or their proxy).
      Seventeen PD cases from Olmsted County, all 20 referral cases, and 16 unaffected
      subjects participated in the interview (total = 37 with PD and 16 unaffected
      subjects); 36 interviews (24 PD) were with a proxy and 17 (13 PD) were direct.
      Questions regarding "poor balance," "trouble buttoning," and "trouble arising"
      had the highest sensitivity; questions regarding "shaking," "feet stuck to the
      floor," "softer voice," and "smaller writing" had the highest specificity. A
      combination of any four symptoms yielded the best balance between sensitivity
      (89%) and specificity (88%). Although the questionnaire appears to be useful both
      as a screening and as a diagnostic tool, it failed to reach complete accuracy,
      and it should be used in the context of a more complex case-finding strategy.

PMID- 9636002
TI  - Instructions for editors: a "revenge fantasy".

PMID- 9636003
TI  - Zeta and delta: critical descriptive boundaries in statistical analysis.

PMID- 9636004
TI  - Is HDR brachytherapy for carcinoma of the uterine cervix high-throughput but high
      risk?

PMID- 9636005
TI  - High and low dose-rate brachytherapy for cervical carcinoma.
AB  - For the brachytherapy component of the radiation treatment of cervical carcinoma,
      high dose rate (HDR) is slowly replacing conventional low dose rate (LDR) due
      primarily to radiation safety and other physical benefits attributed to the HDR
      modality. Many radiation oncologists are reluctant to make this change because of
      perceived radiobiological disadvantages of HDR. However, in clinical practice HDR
      appears to be as effective as LDR but with a lower risk of late complications, as
      demonstrated by one randomized clinical trial and two comprehensive literature
      and practice surveys. The reason for this appears to be that the radiobiological
      disadvantages of HDR are outweighed by the physical advantages.

PMID- 9636006
TI  - Radiation-induced changes in a cell's program for life.

PMID- 9636007
TI  - Programmed cellular response to ionizing radiation damage.
AB  - Three forms of radiation response were investigated to evaluate the hypothesis
      that cellular radiation response is the result of active molecular signaling and
      not simply a passive physicochemical process. The decision whether or not a cell
      should respond to radiation-induced damage either by induction of rescue systems,
      e.g. mobilization of repair proteins, or induction of suicide mechanisms, e.g.
      programmed cell death, appears to be the expression of intricate cellular
      biochemistry. A cell must recognize damage in its genetic material and then
      activate the appropriate responses. Cell type is important; the response of a
      fibroblast to radiation damage is both quantitatively and qualitatively different
      from that of a lymphocyte. The programmed component of radiation response is
      significant in radiation oncology and predicted to create unique opportunities
      for enhanced treatment success.

PMID- 9636009
TI  - Fractionation effect on radiation-induced growth retardation of tibia in rabbits
      and rats.
AB  - A study of the sensitivity to fractionation of the growing tibia of rabbits and
      rats was conducted by comparing the growth of the treated right bone to that of
      the untreated left side in each individual animal using radiographic
      measurements. The experimental endpoint was the percentage of normal growth 24
      weeks after irradiation in rabbits and 14 weeks after treatment in rats. The
      results show clear dose-response relationships in all experimental arms. A clear
      cut fractionation effect was demonstrated in both species. The alpha/beta-ratios
      determined by maximum likelihood analysis according to the LQ-model with graded
      responses were 3.2 Gy (95% C.I. 1.1; 5.6) in rabbits and 6.9 Gy (5.3; 8.7) in
      rats, when all data were included in the calculations. When single-dose data were
      excluded the alpha/beta-values were -0.6 Gy (-3.1; 2.3) in rabbits and 5.0 Gy
      (3.5; 7.0) in rats. Our data provide further evidence that low doses per fraction
      should be used when irradiation of the epiphysis cannot be avoided in pediatric
      patients.

PMID- 9636008
TI  - Radiotherapy combined with transcatheter arterial infusion chemotherapy for
      locally advanced cervical cancer.
AB  - Twenty-four patients with locally advanced cervical cancer were treated with
      radiation therapy (RT) and transcatheter arterial infusion (TAI) chemotherapy,
      while 22 patients were treated with RT alone. RT consisted of a combination of
      external irradiation and high-dose-rate intracavitary brachytherapy. TAI therapy
      consisted of two sessions using cisplatin and pirarubicin, performed concurrently
      during the periods of external irradiation. The local-regional control rates at 1
      year for the patients treated with RT plus TAI and for those treated with RT
      alone were 87.5% and 58.3%, respectively (p < 0.05). The 3-year cause-specific
      survival (CSS) rates for RT plus TAI, and RT alone were 67.1% and 55.9%,
      respectively (p = n.s.). The 3-year CSS rate for the 14 patients treated with RT
      and TAI who had well- or moderately differentiated squamous cell carcinoma
      without pelvic lymph node swelling was 100%, while that for the 19 patients with
      the same background treated with RT alone was 49% (p < 0.01). Radiation therapy
      combined with TAI appears to be an effective and safe treatment modality for
      patients with locally advanced cervical cancer.

PMID- 9636010
TI  - A quality assurance network in Central European countries--radiotherapy
      infrastructure.
AB  - A survey of the infrastructure in radiotherapy centres in three Central European
      countries has been performed as a first step in the development of a quality
      assurance network. Data concerning radiotherapy equipment, staff and number of
      patients treated in most of the radiotherapy centres from Czech Republic, Poland
      and Hungary were collected at the beginning of 1994. Equipment data have shown
      that 35% of 182 treatment units are conventional x-ray units, 35% 60Co units, 19%
      linear accelerators, 7% 137Cs units and 4% betatrons. About 47% of high energy
      units are older than 12 years and about 20% older than 21 years. An important
      number of centres still have no simulator which would constitute an important
      handicap to carry out adequate radiotherapy. The number of treatment planning
      systems has also been registered; 44% being PC-based systems with locally
      developed software. Large variations are observed in the number of patients
      treated per year, per high energy unit, but 12/47 centres treat more than 700
      patients per year and unit. On the average, staffing seems adequate in numbers
      though there are wide variations. The main limitation of radiotherapy
      infrastructure in the Central European countries is the low number of linear
      accelerators and simulators and the advanced age of therapy units.

PMID- 9636011
TI  - Recurrence after different primary treatment for cancer of the supraglottic
      larynx.
AB  - Retrospective analysis of patient records at two hospitals was performed with the
      principal goal of clarifying the role of primary radiotherapy ill patients with
      squamous cell carcinoma of the supraglottic larynx. Primary surgery was
      frequently performed during the first period from 1958 to 1978. Primary
      radiotherapy with surgery in reserve was the prevailing therapy during the second
      period from 1978 to 1993. Fewer recurrences were observed during the second
      period. The improved results were apparent mainly in patients with the more
      advanced stages (III, T4N0 and T4N1). Analysis of many factors suggest that the
      more frequent choice of primary radiotherapy with surgery in reserve, or applied
      as preoperative treatment, with optimal dosage and technique, might have
      contributed to the improved results.

PMID- 9636012
TI  - Avascular necrosis of bone--a complication of aggressive therapy for acute
      lymphoblastic leukemia.
AB  - The purpose of the present paper was to report cases of avascular necrosis of
      bone (AVNB) arising as a complication of chemotherapy for acute lymphoblastic
      leukemia (ALL). X-rays and 99mtechnicium-MDP bone scans were performed on
      patients with symptoms of bone pain, whereby five patients out of 850 patients
      were detected to have avascular necrosis of the femoral head. All had received
      aggressive chemotherapy with steroids. Two patients were still on therapy for the
      primary disease. In these patients further chemotherapy was continued without
      steroids. The median period from diagnosis of ALL to development of AVNB was 29
      months. Three patients underwent corrective surgical procedures. To conclude, the
      data suggest that patients receiving combination chemotherapy, especially those
      with high cumulative doses, run a risk of developing AVNB. Awareness of this
      complication is important in order to have an early diagnosis so as to limit
      disability.

PMID- 9636013
TI  - Growth hormone reduces mortality and bacterial translocation in irradiated rats.
AB  - Growth hormone stimulates the growth of intestinal mucosa and may reduce the
      severity of injury caused by radiation. Male Wistar rats underwent abdominal
      irradiation (12 Gy) and were treated with either human growth hormone (hGH) or
      saline, and sacrificed at day 4 or 7 post-irradiation. Bacterial translocation,
      and the ileal mucosal thickness, proliferation, and disaccharidase activity were
      assessed. Mortality was 65% in irradiated animals, whereas hGH caused a decrement
      (29%, p < 0.05). Bacterial translocation was also reduced by hGH (p < 0.05).
      Treating irradiated rats with hGH prevented body weight loss (p < 0.05). Mucosal
      thickness increased faster in irradiated hGH-treated animals. The proliferative
      index showed an increment in hGH-treated animals (p < 0.05). Giving hGH to
      irradiated rats prevented decrease in sucrose activity, and increment in lactase
      activity. In conclusion, giving hGH to irradiated rats promotes the adaptative
      process of the intestine and acute radiation-related negative effects, including
      mortality, bacterial translocation, and weight loss.

PMID- 9636014
TI  - Phase II study of estramustine and vinorelbine in hormone-refractory prostate
      carcinoma patients.
AB  - The purpose of this study was to evaluate the antitumor activity of vinorelbine
      and oral estramustine phosphate in patients with metastatic, hormone-refractory
      prostate cancer. We evaluated the activity of this association using the
      following schedule: estramustine phosphate 600 mg/m2/day orally days 1-42 and
      vinorelbine 25 mg/m1 days 1, 8, 22, 29 cycles repeated every 56 days. Twenty-five
      patients were included in the study, 24 being evaluable for response and 25 for
      toxicity. Out of 5 patients with measurable disease, none had an objective
      response. Of the 24 assessable patients with bone metastases, 9 patients had a >
      or = 65% decline in pretreatment prostate-specific antigen (PSA) level, stable
      disease was observed in 10 and 5 patients progressed. Toxicities were minimal.
      Anemia was observed in 5 patients, alopecia in 4 and nausea and vomiting was
      observed in 6 patients. Anorexia and weight loss of more than 10% were observed
      in 2 patients. This combination is active and well tolerated in hormone-resistant
      prostate cancer. These results support the therapeutic strategy of combining
      agents that impair microtubule function.

PMID- 9636015
TI  - Alterations of the immunoglobulin heavy chain locus in progressive B-cell
      lymphomas.
AB  - Twenty-two patients with relapsed or progressive B-cell lymphomas (BCL) were
      analysed for alterations in the rearrangement status in the immunoglobulin heavy
      (IgH) chain gene in samples obtained on different occasions during the course of
      the disease. The analysis was performed using Southern blot hybridization of the
      IgH gene and polymerase chain reaction (PCR) amplification of the VH gene
      families combined with single-strand conformation polymorphism (SSCP) analysis.
      Using Southern blot analysis, we found that all 22 lymphomas displayed clonal IgH
      rearrangements, and changes during tumour progression occurred in 8 cases. These
      alterations were mainly observed in cases with follicular or transformed
      lymphomas. More than one malignant (sub)clone, indicated by more than two
      rearranged bands, was detected in one case at diagnosis and in three cases at
      relapse. Outgrowth of subclones with divergent rearrangement patterns in
      different compartments was also observed in 2 out of 8 cases. PCR-SSCP analysis
      indicated that all 15 cases studied displayed clonal rearrangements and in 6
      cases altered rearrangement patterns were detected in later samples. Southern
      blotting and PCR-SCCP analysis gave equivalent results. No association was found
      between time to relapse or survival time and alterations in rearrangement
      pattern. The present study illustrates that the neoplastic cell clones in BCL
      often display alterations in their IgH locus, but the significance of this
      feature remains to be clarified.

PMID- 9636016
TI  - Radiation-induced insufficiency fractures after definitive prostate cancer
      radiotherapy.

PMID- 9636017
TI  - Discordant washout of 99mTc sestamibi and 99mTc tetrofosmin in a patient with
      mediastinal seminoma.

PMID- 9636018
TI  - Multiple smooth-muscle neoplasm and thyroid carcinoma in an adult with AIDS.

PMID- 9636019
TI  - Breast angiosarcoma after conservative surgery, radiotherapy and prosthesis
      implant.

PMID- 9636020
TI  - Leiomyosarcoma of the gallbladder--a case report and review of the literature.

PMID- 9636021
TI  - Solution structure of the transmembrane H+-transporting subunit c of the F1F0 ATP
      synthase.
AB  - Subunit c is the H+-translocating component of the F1F0 ATP synthase complex. H+
      transport is coupled to conformational changes that ultimately lead to ATP
      synthesis by the enzyme. The properties of the monomeric subunit in a single
      phase solution of chloroform-methanol-water (4:4:1) have been shown to mimic
      those of the protein in the native complex. Triple resonance NMR experiments were
      used to determine the complete structure of monomeric subunit c in this solvent
      mixture. The structure of the protein was defined by >2000 interproton distances,
      64 (3)JN alpha, and 43 hydrogen-bonding NMR-derived restraints. The root mean
      squared deviation for the backbone atoms of the two transmembrane helices was
      0.63 A. The protein folds as a hairpin of two antiparallel helical segments,
      connected by a short structured loop. The conserved Arg41-Gln42-Pro43 form the
      top of this loop. The essential H+-transporting Asp61 residue is located at a
      slight break in the middle of the C-terminal helix, just prior to Pro64. The C
      terminal helix changes direction by 30 +/- 5 degrees at the conserved Pro64. In
      its protonated form, the Asp61 lies in a cavity created by the absence of side
      chains at Gly23 and Gly27 in the N-terminal helix. The shape and charge
      distribution of the molecular surface of the monomeric protein suggest a packing
      arrangement for the oligomeric protein in the F0 complex, with the front face of
      one monomer packing favorably against the back face of a second monomer. The
      packing suggests that the proton (cation) binding site lies between packed pairs
      of adjacent subunit c.

PMID- 9636022
TI  - Carbamoyl phosphate synthetase: caught in the act of glutamine hydrolysis.
AB  - Carbamoyl phosphate synthetase from Escherichia coli catalyzes the production of
      carbamoyl phosphate from two molecules of Mg2+ATP, one molecule of bicarbonate,
      and one molecule of glutamine. The enzyme consists of two polypeptide chains
      referred to as the large and small subunits. While the large subunit provides the
      active sites responsible for the binding of nucleotides and other effector
      ligands, the small subunit contains those amino acid residues that catalyze the
      hydrolysis of glutamine to glutamate and ammonia. From both amino acid sequence
      analyses and structural studies it is now known that the small subunit belongs to
      the class I amidotransferase family of enzymes. Numerous biochemical studies have
      suggested that the reaction mechanism of the small subunit proceeds through the
      formation of the glutamyl thioester intermediate and that both Cys 269 and His
      353 are critical for catalysis. Here we describe the X-ray crystallographic
      structure of carbamoyl phosphate synthetase from E. coli in which His 353 has
      been replaced with an asparagine residue. Crystals employed in the investigation
      were grown in the presence of glutamine, and the model has been refined to a
      crystallographic R-factor of 19.1% for all measured X-ray data from 30 to 1.8 A
      resolution. The active site of the small subunit clearly contains a covalently
      bound thioester intermediate at Cys 269, and indeed, this investigation provides
      the first direct structural observation of an enzyme intermediate in the
      amidotransferase family.

PMID- 9636023
TI  - Autocatalytic formation of a hydroxy group at C beta of trp171 in lignin
      peroxidase.
AB  - In the high-resolution crystal structures of two lignin peroxidase isozymes from
      the white rot fungus Phanerochaete chrysosporium a significant electron density
      at single bond distance from the C beta of Trp171 was observed and interpreted as
      a hydroxy group. To further clarify the nature of this feature, we carried out
      tryptic digestion of the enzyme and isolated the Trp171 containing peptide. Under
      ambient conditions, this peptide shows an absorbance spectrum typical of
      tryptophan. At elevated temperature, however, the formation of an unusual
      absorbance spectrum with lambda max = 333 nm can be followed that is identical to
      that of N-acetyl-alpha, beta-didehydrotryptophanamide, resulting upon water
      elimination from beta-hydroxy tryptophan. The Trp171 containing tryptic peptide
      isolated from the recombinant and refolded lignin peroxidase produced from
      Escherichia coli does not contain the characteristic 333 nm absorbance band at
      any temperature. However, treatment with 3 equiv of H2O2 leads to complete
      hydroxylation of Trp171. Reducing substrates compete with this process, e.g., in
      the presence of 0.5 mM veratryl alcohol, about 7 equiv of H2O2 is necessary for
      complete modification. We conclude that the hydroxylation at the C beta of Trp171
      is an autocatalytic reaction which occurs readily under conditions of natural
      turnover, e.g., in the ligninolytic cultures of P. chrysosporium, which are known
      to contain an oxidase-based H2O2-generating system. No dependence on dioxygen was
      found for this oxidative process. Chemical modification of fungal lignin
      peroxidase with the tryptophan-specific agent N-bromo succinimide leads to a
      drastically reduced activity with respect to the substrate veratryl alcohol. This
      suggests that Trp171 is involved in catalysis and that electron transfer from
      this surface residue to the oxidized heme cofactor is possible under steady-state
      conditions.

PMID- 9636024
TI  - Site-directed mutagenesis of the conserved threonine (Thr243) of the distal helix
      of fungal cytochrome P450nor.
AB  - Cytochrome P450nor (P450nor) is a heme enzyme which catalyzes NO reduction in
      denitrifying fungi. Threonine 243 (Thr243) of P450nor, which corresponds to the
      conserved threonine of monooxygenase cytochrome P450s, was replaced by 18
      different amino acids via site-directed mutagenesis. The mutation did not
      seriously affect the optical absorption and the CD spectral properties of the
      enzyme in several oxidation, ligation, or spin states or the association rate
      constant for association of NO with the ferric iron, suggesting subtle and local
      structural changes in the heme environment on Thr243 mutation. However, the NO
      reduction activity was dramatically altered by Thr243 mutation, depending on the
      properties of the replaced amino acids. The catalytic activity, as measured by
      N2O formation and NADH consumption, was considerably retained on substitution of
      Asn, Ser, and Gly for Thr243, while it was profoundly decreased or lost on
      substitution with other amino acids. Kinetic analysis of the reaction of the
      enzymes with NO and NADH indicated that the decrease in the enzymatic activity
      upon Thr243 mutation mainly results from a decrease in the rate of reduction of
      the ferric-NO complex with NADH. On the basis of these enzymatic, kinetic, and
      spectroscopic results, as well as on the basis of the crystal data for native
      P450nor [Park, S.-Y., et al. (1997) Nat. Struct. Biol. 4, 827-832], the role of
      the conserved threonine at the 243 position in the NO reduction reaction by
      P450nor is discussed. We also discuss structural similarities or differences in
      the vicinity of the conserved threonine between P450nor and other monooxygenase
      P450s.

PMID- 9636025
TI  - Design of a novel P450: a functional bacterial-human cytochrome P450 chimera.
AB  - We report the construction of a functional chimera from approximately 50%
      bacterial (cytosolic) cytochrome P450cam and 50% mammalian (membrane-bound)
      cytochrome P450 2C9. The chimeric protein shows a reduced CO-difference spectrum
      absorption at 446 nm, and circular dichroism spectra indicate that the protein is
      globular. The protein is soluble and catalyzes the oxidation of 4-chlorotoluene
      using molecular oxygen and reducing equivalents from bacterial putidaredoxin and
      putidaredoxin reductase. This chimera provides a novel method for addressing
      structure-function issues and may prove useful in the design of oxidants for
      benign and stereospecific synthesis, as well as catalysts for bioremediation of
      polluted areas. Furthermore, these results provide the first evidence that
      bacterial P450 enzymes and mammalian P450 enzymes are likely to share a common
      tertiary structure.

PMID- 9636026
TI  - Colocalization of heparin and receptor binding sites on keratinocyte growth
      factor.
AB  - Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor
      (FGF) family. FGFs are also known as heparin-binding growth factors because they
      bind to heparin and their physical and biological properties are modulated by
      heparin. Consistent with a role as a paracrine effector, KGF is produced by cells
      of mesenchymal origin but is active primarily, if not exclusively, on epithelial
      cells. KGF is involved in a variety of physiological processes, including
      proliferation, differentiation, wound healing, and cytoprotection. To identify
      regions in KGF that contribute to heparin and tyrosine kinase receptor
      interactions, nine peptides spanning defined motifs in the predicted structure of
      KGF were synthesized, and their heparin and receptor binding properties were
      analyzed. Peptides at the amino and carboxyl termini bound heparin, and one
      peptide showed relative binding comparable to that of KGF. Competitive binding
      studies showed that this peptide along with two other overlapping peptides
      specifically displaced KGF bound to the KGF receptor. These three peptides were
      also selectively recognized by a neutralizing monoclonal antibody against KGF,
      though only in the presence of heparin. Together, these data suggest that the
      sites for heparin and receptor binding both reside in the amino and carboxyl
      termini of KGF, which are spatially juxtaposed in the predicted three-dimensional
      structure of this molecule.

PMID- 9636027
TI  - Thermodynamics of the interaction of human immunoglobulin E with its high
      affinity receptor Fc epsilon RI.
AB  - We have employed isothermal titration calorimetry (ITC) and circular dichroism
      (CD) spectroscopy to characterize the binding of soluble fragments of IgE (IgE-Fc
      and Fc epsilon 3-4) to a soluble fragment of the high-affinity receptor Fc
      epsilon RI alpha-chain (sFc epsilon RI alpha). The thermodynamic parameters for
      the interaction of IgE-Fc and Fc epsilon 3-4 with sFc epsilon RI alpha,
      determined using ITC, confirm the earlier conclusion that the C epsilon 2 domain
      is not involved in the interaction and that the stoichiometry of both complexes
      is 1:1. For both IgE-Fc and Fc epsilon 3-4, the value of Delta H degrees is -36.9
      +/- 4.6 kcal mol-1 at 37.3 degreesC and Delta Cp degrees is -820 +/- 120 cal mol
      1 K-1. The temperature at which DeltaS degrees is zero is 284 +/- 1 K, indicating
      that the entropy contribution to the thermodynamics of association is unfavorable
      at physiological temperature. Of particular interest is the large value of Delta
      Cp degrees. The large surface area of IgE and Fc epsilon RI alpha that is
      implicated in complex formation from previous mutagenesis studies on the two
      proteins may account in part for the magnitude of Delta Cp degrees. Additional
      contributions may arise from hydration within the binding site and changes in
      tertiary structure of the individual components of the complex. However, the CD
      spectra of IgE, IgE-Fc, and Fc epsilon 3-4 complexes with sFc epsilon RI alpha
      are merely the sum of the spectra of their individual components, indicating that
      the secondary structure of the immunoglobulin domain folds are preserved on
      complex formation. Thus, any change in tertiary structure must be limited to the
      relative disposition of the immunoglobulin domains C epsilon 3 and C epsilon 4 in
      IgE and the two immunoglobulin-like domains in the alpha-chain of Fc epsilon RI.

PMID- 9636028
TI  - Molecular mimics of insulin-like growth factor 1 (IGF-1) for inhibiting IGF-1:
      IGF-binding protein interactions.
AB  - IGF-1 (insulin-like growth factor 1) is a 70-residue protein hormone which has
      both metabolic and mitogenic activities mediated through IGF-1 binding to cell
      surface receptors. However, an unrelated class of proteins, the IGF-binding
      proteins (IGFBPs) also bind IGF-1 in the serum and tissues and block or modulate
      its activity in vivo. Therefore, inhibitors of the IGFBPs can alter the
      distribution between free and bound IGF-1 [Loddick, S. A., Liu, X.-J., Lu, Z.-X.,
      Liu, C., Behan, D. P., Chalmers, D. C., Foster, A. C., Vale, W. W., Ling, N., and
      De Souza, E. B. (1998) Proc. Natl. Acad. Sci. U.S.A. 95, 1894-1898] and
      potentially affect the distribution of IGF-1 among body tissues. We report here
      that phage-displayed peptide libraries have yielded a peptide that binds IGFBP-1
      and produces IGF-like activity at sub-micromolar concentrations. The 14-residue
      peptide has an extremely well-defined solution conformation that can aid in the
      design of smaller, orally active compounds. Interestingly, the peptide structure
      contains a helix, as does one region of IGF-1 previously implicated in IGFBP
      binding, yet displays side chains different from those of the IGF-1 helix I.
      Furthermore, an IGF-1 variant lacking receptor-signaling activity in vitro is
      shown here to produce IGF-like mitogenic and metabolic activity in vivo. These
      results suggest that small antagonist mimetics of protein ligands, identified by
      binding selection to otherwise inhibitory factors, may be useful as indirect
      agonists for a variety of therapeutic applications.

PMID- 9636029
TI  - Competitive inhibition of MAP kinase activation by a peptide representing the
      alpha C helix of ERK.
AB  - On the basis of the crystal structure of the MEK substrate ERK, we have
      synthesized a 15 amino acid peptide representing the alpha C helix of human ERK1.
      We find this peptide to be an inhibitor of ERK phosphorylation by its upstream
      activator MEK. Circular dichroic spectroscopy indicates that the peptide has
      little secondary structure in aqueous buffer, but can readily adopt an alpha
      helical structure in aprotic solvent. Steady-state kinetic analysis indicates
      that the peptide serves as a competitive inhibitor of ERK binding to MEK, with a
      dissociation constant, Ki, of 0.84 microM. Together with ATP-competitive
      inhibitors of MEK, we have used this peptide to define the kinetic mechanism of
      MEK catalysis. These studies reveal that MEK operates through a bi-bi random
      ordered sequential mechanism. The synthetic peptide inhibits also the
      phosphorylation of p38 and ERK by the upstream activator MKK3, but is at least 3
      fold less potent as an inhibitor of SEK activation of JNK1. Interestingly, the
      peptide also showed some ability to inhibit ERK-mediated phosphorylation of
      myelin basic protein, but was inactive as an inhibitor of the unrelated kinases
      Raf, Abl, and PKA. These results imply that the alpha C helix is an important
      locus of interaction for the formation of a MEK-ERK complex. The alpha C helix
      cannot, however, be the sole determinant of activator selectivity among the MAP
      kinases. Molecules designed to target the alpha C helix binding pocket of MAP
      kinase activators may provide a novel means of inhibiting these signal
      transducers.

PMID- 9636031
TI  - Product inhibition of the hepatitis C virus NS3 protease.
AB  - The nonstructural protein NS3 of the hepatitis C virus (HCV) harbors a serine
      protease domain that is responsible for most of the processing events of the
      nonstructural region of the polyprotein. Its inhibition is presently regarded as
      a promising strategy for coping with the disease caused by HCV. In this work, we
      show that the NS3 protease undergoes inhibition by the N-terminal cleavage
      products of substrate peptides corresponding to the NS4A-NS4B, NS4B-NS5A, and
      NS5A-NS5B cleavage sites, whereas no inhibition is observed with a cleavage
      product of the intramolecular NS3-NS4A junction. The Ki values of the hexamer
      inhibitory products [Ki(NS4A) = 0.6 microM, Ki(NS5A) = 1.4 microM, and Ki(NS4B) =
      180 microM] are lower than the Km values of the respective substrate peptides
      [Km(NS4A-NS4B) = 10 microM, Km(NS5A-NS5B) = 3.8 microM, and Km(NS4B-NS5A) > 1000
      microM]. Mutagenesis experiments have identified Lys136 as an important
      determinant for product binding. The phenomenon of product inhibition can be
      exploited to optimize peptide inhibitors of NS3 protease activity that may be
      useful in drug development.

PMID- 9636030
TI  - His...Asp catalytic dyad of ribonuclease A: structure and function of the wild
      type, D121N, and D121A enzymes.
AB  - The side chains of histidine and aspartate residues form a hydrogen bond in the
      active sites of many enzymes. In serine proteases, the His...Asp hydrogen bond of
      the catalytic triad is known to contribute greatly to catalysis, perhaps via the
      formation of a low-barrier hydrogen bond. In bovine pancreatic ribonuclease A
      (RNase A), the His...Asp dyad is composed of His119 and Asp121. Previously, site
      directed mutagenesis was used to show that His119 has a fundamental role, to act
      as an acid during catalysis of RNA cleavage [Thompson, J. E., and Raines, R. T.
      (1994) J. Am. Chem. Soc. 116, 5467-5468]. Here, Asp121 was replaced with an
      asparagine or alanine residue. The crystalline structures of the two variants
      were determined by X-ray diffraction analysis to a resolution of 1.6 A with an R
      factor of 0.18. Replacing Asp121 with an asparagine or alanine residue does not
      perturb the overall conformation of the enzyme. In the structure of D121N RNase
      A, Ndelta rather than Odelta of Asn121 faces His119. This alignment in the
      crystalline state is unlikely to exist in solution because catalysis by the D121N
      variant is not compromised severely. The steady-state kinetic parameters for
      catalysis by the wild-type and variant enzymes were determined for the cleavage
      of uridylyl(3'-->5')adenosine and poly(cytidylic acid), and for the hydrolysis of
      uridine 2',3'-cyclic phosphate. Replacing Asp121 decreases the values of kcat/Km
      and kcat for cleavage by 10-fold (D121N) and 10(2)-fold (D121A). Replacing Asp121
      also decreases the values of kcat/Km and kcat for hydrolysis by 10(0. 5)-fold
      (D121N) and 10-fold (D121A) but has no other effect on the pH-rate profiles for
      hydrolysis. There is no evidence for the formation of a low-barrier hydrogen bond
      between His119 and either an aspartate or an asparagine residue at position 121.
      Apparently, the major role of Asp121 is to orient the proper tautomer of His119
      for catalysis. Thus, the mere presence of a His...Asp dyad in an enzymic active
      site is not a mandate for its being crucial in effecting catalysis.

PMID- 9636032
TI  - Potent peptide inhibitors of human hepatitis C virus NS3 protease are obtained by
      optimizing the cleavage products.
AB  - In the absence of a broadly effective cure for hepatitis caused by hepatitis C
      virus (HCV), much effort is currently devoted to the search for inhibitors of the
      virally encoded protease NS3. This chymotrypsin-like serine protease is required
      for the maturation of the viral polyprotein, cleaving it at the NS3-NS4A, NS4A
      NS4B, NS4B-NS5A, and NS5A-NS5B sites. In the course of our studies on the
      substrate specificity of NS3, we found that the products of cleavage
      corresponding to the P6-P1 region of the substrates act as competitive inhibitors
      of the enzyme, with IC50s ranging from 360 to 1 microM. A detailed study of
      product inhibition by the natural NS3 substrates is described in the preceding
      paper [Steinkuhler, C., et al. (1997) Biochemistry 37, 8899-8905]. Here we report
      the results of a study of the structure-activity relationship of the NS3 product
      inhibitors, which suggest that the mode of binding of the P region-derived
      products is similar to the ground-state binding of the corresponding substrates,
      with additional binding energy provided by the C-terminal carboxylate. Optimal
      binding requires a dual anchor: an "acid anchor" at the N terminus and a "P1
      anchor" at the C-terminal part of the molecule. We have then optimized the
      sequence of the product inhibitors by using single mutations and combinatorial
      peptide libraries based on the most potent natural product, Ac-Asp-Glu-Met-Glu
      Glu-Cys-OH (Ki = 0.6 microM), derived from cleavage at the NS4A-NS4B junction. By
      sequentially optimizing positions P2, P4, P3, and P5, we obtained several
      nanomolar inhibitors of the enzyme. These compounds are useful both as a starting
      point for the development of peptidomimetic drugs and as structural probes for
      investigating the substrate binding site of NS3 by modeling, NMR, and
      crystallography.

PMID- 9636033
TI  - Hydrophobic core substitutions in calbindin D9k: effects on stability and
      structure.
AB  - The effects of hydrophobic core mutations on the stability and structure of the
      four-helix calcium-binding protein, calbindin D9k, have been investigated. Eleven
      mutations involving eight residues distributed within the hydrophobic core of
      calbindin D9k were examined. Stabilities were measured by denaturant and thermal
      induced unfolding monitored by circular dichroism spectroscopy. The mutations
      were found to exert large effects on the stability with midpoints in the urea
      induced unfolding varying from 1.8 M for Leu23 --> Gly up to 6.6 M for Val70 -->
      Leu and free energies of unfolding in the absence of denaturant ranging from 6.6
      to 27.4 kJ/mol for the Phe66 --> Ala mutant and the wild-type, respectively. A
      significant correlation was found between the difference in free energy of
      unfolding (Delta Delta GNU) and the change in the surface area of the side chain
      caused by the mutation, in agreement with other studies. Notably, both increases
      and decreases in side-chain surface area caused quantitatively equivalent effects
      on the stability. In other words, a correlation between the absolute value of the
      change in the surface of the side chain and Delta DeltaGNU was observed with a
      value of approximately 0.14 kJ M-1 A-2. The generality of this observation is
      discussed. Significant effects on the cooperativity of the unfolding reaction
      were also observed. However, a correlation between the cooperativity and Delta
      Delta GNU, which has been reported in other systems as an indication of effects
      of mutations on the unfolded state, was not observed for calbindin D9k. Despite
      the large effects on Delta Delta GNU and cooperativity, the structures of the
      mutants in the native form remained intact as indicated by circular dichroism,
      NMR, and fluorescence measurements. The structural response to calcium-binding
      was also conserved. The following paper in this issue [Kragelund, B. B., et al.
      (1998) Biochemistry 37, 8926-8937] examines the effects of these mutations on the
      calcium binding properties of calbindin D9k.

PMID- 9636034
TI  - Hydrophobic core substitutions in calbindin D9k: effects on Ca2+ binding and
      dissociation.
AB  - Hydrophobic core residues have a marked influence on the Ca2+-binding properties
      of calbindin D9k, even though there are no direct contacts between these residues
      and the bound Ca2+ ions. Eleven different mutants with substitutions in the
      hydrophobic core were produced, and their equilibrium Ca2+-binding constants
      measured from Ca2+ titrations in the presence of chromophoric chelators. The Ca2+
      dissociation rate constants were estimated from Ca2+ titrations followed by 1H
      NMR1 and were measured more accurately using stopped-flow fluorescence. The
      parameters were measured at four KCl concentrations to assess the salt dependence
      of the perturbations. The high similarity between the NMR spectra of mutants and
      wild-type calbindin D9k suggests that the structure is largely unperturbed by the
      substitutions. More detailed NMR investigations of the mutant in which Val61 is
      substituted by Ala showed that the mutation causes only very minimal
      perturbations in the immediate vicinity of residue 61. Substitutions of alanines
      or glycines for bulky residues in the center of the core were found to have
      significant effects on both Ca2+ affinity and dissociation rates. These
      substitutions caused a reduction in affinity and an increase in off-rate. Small
      effects, both increases and decreases, were observed for substitutions involving
      residues far from the Ca2+ sites and toward the outer part of the hydrophobic
      core. The mutant with the substitution Phe66 --> Trp behaved differently from all
      other mutants, and displayed a 25-fold increase in overall affinity of binding
      two Ca2+ ions and a 6-fold reduction in calcium dissociation rate. A strong
      correlation (R = 0.94) was found between the observed Ca2+-dissociation rates and
      affinities, as well as between the salt dependence of the off-rate and the
      distance to the nearest Ca2+-coordinating atom. There was also a strong
      correlation (R = 0.95) between the Ca2+ affinity and stability of the Ca2+ state
      and a correlation (R = 0. 69) between the Ca2+ affinity and stability of the apo
      state, as calculated from the results in the present and preceding paper in this
      issue [Julenius, K., Thulin, E., Linse, S., and Finn, B. E. (1998) Biochemistry
      37, 8915-8925]. The change in salt dependencies of koff and cooperativity were
      most pronounced for residues completely buried in the core of the protein
      (solvent accessible surface area approximately 0). Altogether, the results
      suggest that the hydrophobic core residues promote Ca2+ binding both by
      contributing to the preformation of the Ca2+ sites in the apo state and by
      preferentially stabilizing the Ca2+-bound state.

PMID- 9636035
TI  - Incorporation of tryptophan analogues into staphylococcal nuclease, its V66W
      mutant, and Delta 137-149 fragment: spectroscopic studies.
AB  - We have biosynthetically incorporated several tryptophan analogues into three
      forms of Staphylococcal nuclease to investigate the spectroscopic characteristics
      of these "intrinsic" probes and their effect on the structure of the proteins.
      The set of tryptophan analogues includes 5-hydroxytryptophan, 7-azatryptophan, 4
      fluorotryptophan, 5-fluorotryptophan, and 6-fluorotryptophan. 5-Hydroxytryptophan
      and 7-azatryptophan have red-shifted absorbance spectra, and the latter has a red
      shifted fluorescence, which is very sensitive to its environment (being heavily
      quenched in water). The fluorotryptophans can serve as 19F NMR probes, and 4
      fluorotryptophan has a very low fluorescence quantum yield, thus making it a
      "knock-out" fluorescence analogue. The set of proteins studied includes wild-type
      nuclease, which has a single tryptophan site at position 140; its V66W mutant,
      which has a second tryptophan at position 66; and the Delta 137-149 fragment,
      V66W', which only has a tryptophan at position 66. The environments of positions
      66 and 140 are significantly different; position 140 is near the end of the long
      C-terminal alpha-helix and is moderately solvent-exposed, whereas position 66 is
      in the beta-barrel core region of the protein and is surrounded by apolar side
      chains. Absorbance and 19F NMR spectra are used to estimate the extent of
      analogue incorporation for each protein. Steady-state and time-resolved
      fluorescence data are reported to characterize the emission of the analogues in
      these positions in the three proteins and to develop the use of the analogues as
      probes of protein structure and dynamics. Circular dichroism spectra are reported
      to show that, in all but a couple of cases, the secondary structure of the
      proteins containing the analogues is not significantly perturbed by the probes.
      Additionally, fluorescence anisotropy decay data show the variants of wild-type
      nuclease to have a rotational correlation time similar to that of tryptophan
      containing nuclease.

PMID- 9636036
TI  - Incorporation of tryptophan analogues into staphylococcal nuclease: stability
      toward thermal and guanidine-HCl induced unfolding.
AB  - The tryptophan analogues, 5-hydroxytryptophan, 7-azatryptophan, 4
      fluorotryptophan, 5-fluorotryptophan, and 6-fluorotryptophan, have been
      biosynthetically incorporated into Staphylococcal nuclease, its V66W mutant, and
      the Delta 137-149 fragment of the latter mutant. The guanidine-HCl induced
      unfolding and thermal unfolding of these proteins were studied to characterize
      the effect of incorporation of these tryptophan analogues on the thermodynamic
      stability of the proteins. The three proteins have tryptophan residues at
      positions 140 (in wild type) and 66 (in the Delta 137-149 fragment of V66W) and
      at both positions (in V66W). The unfolding data show that 5-hydroxytryptophan
      does not perturb the stability of wild-type nuclease, but it destabilizes the
      fragment and causes the V66W mutant to unfold in a more cooperative manner. 7
      Azatryptophan is found to destabilize all three proteins. 4-Fluorotryptophan is
      slightly stabilizing of the three proteins, but the other two fluorotryptophans
      do not alter the stability of the proteins.

PMID- 9636037
TI  - Phosphorescence and optically detected magnetic resonance characterization of the
      environments of tryptophan analogues in staphylococcal nuclease, its V66W mutant,
      and Delta 137-149 fragment.
AB  - Phosphorescence and optically detected magnetic resonance (ODMR) measurements are
      reported on the triplet states of the tryptophan analogues, 7-azatryptophan
      (7AW), 5-hydroxytryptophan (5HW), and 4-, 5-, and 6-fluorotryptophan (4FW, 5FW,
      6FW), when incorporated at position 140 of wild-type Staphylococcal nuclease (7AW
      nuclease, etc. ), positions 66 and 140 of its V66W mutant (7AW-V66W, etc.), and
      the deletion fragment of the latter, Delta 137-149 (7AW-V66W', etc.). These
      measurements point to the retention of protein structure at position 140 in each
      of the wild-type nuclease analogues. Substitution of the analogue at both
      tryptophan sites of V66W leads to structured sites with differentiated triplet
      state properties for all analogues except 7AW-V66W, whose structure is
      destabilized. 5HW-V66W' is the only fragment that apparently lacks structure at
      position 66. All other V66W' analogues exhibit a structured environment at
      position 66 (4FW-V66W' was not studied), but in each case this site can be
      differentiated readily from the corresponding site in intact V66W. 7AW-V66W' is
      resolved by ODMR into two discrete structures with slightly differing zero field
      splittings (ZFS). Interaction of the protein with 5HW at position 66 of 5HW-V66W
      induces a 2-fold increase in the ZFS E parameter, which is reduced to its normal
      value upon formation of the fragment, 5HW-V66W'. Analogous effects occur for 5FW,
      but on a smaller scale.

PMID- 9636038
TI  - Ionization-reactivity relationships for cysteine thiols in polypeptides.
AB  - Thiol-disulfide exchange reactions are required for many aspects of cellular
      metabolism including the folding of disulfide-bonded proteins, electron transfer,
      and numerous regulatory mechanisms. To identify factors influencing the rates of
      these reactions in polypeptides, the reactivities of Cys thiols in 16 model
      peptides were measured. For each of the peptides, which contained single Cys
      residues with thiol pKas ranging from 7.4 to 9.1, the rates of exchange with four
      disulfide-bonded compounds were measured. In reactions with two of the disulfide
      reagents, cystine and 2-hydroxyethyl disulfide, the peptide thiols displayed
      Bronsted correlations between reaction rate and pKa similar to those observed
      previously with model compounds (betanuc = 0.5 and 0.3, respectively). For two
      reagents with net charges, oxidized glutathione and cystamine, however, the
      apparent Bronsted coefficients were 0 and 0.8, respectively. These observations
      are in striking contrast with those obtained with model compounds, for which the
      Bronsted coefficients for the nucleophilic thiolates are largely independent of
      the disulfide-containing compound. The differences in the apparent Bronsted
      coefficients can be largely accounted for by electrostatic interactions between
      charged groups on the peptides and disulfide reagents and demonstrate that such
      interactions can play a dominant role in determining the rates of thiol-disulfide
      exchange in biological molecules. The results presented here provide an improved
      basis for predicting the rates of these reactions and suggest ways in which
      differences in the rates of competing reactions can be either minimized, to
      simplify the analysis of disulfide-coupled folding reactions, or enhanced, to
      favor formation of particular disulfides.

PMID- 9636039
TI  - Mutational analysis of structural features of rat hormone-sensitive lipase.
AB  - Hormone-sensitive lipase (HSL) is a cytosolic neutral lipase that hydrolyzes
      intracellular stores of triacylglycerols and cholesteryl esters. HSL activity is
      regulated via phosphorylation-dephosphorylation, with cyclic AMP-dependent
      protein kinase increasing activity following phosphorylation of a single serine
      and Ca2+/calmodulin-dependent protein kinase II phosphorylating another serine at
      a basal site. The current studies used site-directed mutagenesis to show that Ser
      563 of rat HSL is phosphorylated by cyclic AMP-dependent protein kinase and that
      Ser-565 is phosphorylated by Ca2+/calmodulin-dependent protein kinase II.
      Mutation of Ser-563-->Ala eliminated HSL hydrolytic activity against cholesteryl
      ester, triacylglycerol, and diacylglycerol substrates to the same extent as
      mutation of Ser-423-->Ala, the presumed catalytic site. Mutation of Ser-565-->Ala
      modestly decreased HSL activity. In contrast, mutation of Ser-563-->Asp preserved
      HSL hydrolytic activity and even increased activity 20% above the control wild
      type enzyme. Molecular modeling of the catalytic pocket of HSL suggested the
      involvement of Val-710. Mutation of Val-710-->Ala resulted in an 85% loss of HSL
      hydrolytic activity. The results of these studies illustrate the importance of
      the presence of a hydroxyl group or negative charge at residue 563, either for
      proper conformation of rat HSL or for proper stabilization of substrate to allow
      maintenance of hydrolytic activity, as well as the importance of the involvement
      of additional amino acids in the catalytic pocket of the enzyme.

PMID- 9636040
TI  - Effects of phosphorylation of serine 40 of tyrosine hydroxylase on binding of
      catecholamines: evidence for a novel regulatory mechanism.
AB  - The effects of phosphorylation at Ser40 of rat tyrosine hydroxylase on the
      affinities of catechols have been determined with both the ferric and ferrous
      forms of the enzyme. Phosphorylation had no effect on the Ki value for the
      inhibition of the ferrous enzyme by either dopamine or DOPA when the initial rate
      of turnover was measured in assays. However, phosphorylation of the ferric enzyme
      resulted in a 17-fold decrease in affinity for DOPA and a 300-fold decrease in
      the affinity for dopamine, while the affinity for dihydroxynaphthalene was
      unchanged. The changes in binding affinity for the two catecholamines were almost
      exclusively due to large increases in the dissociation rate constants upon
      phosphorylation. These results support a novel mechanism for regulation in which
      phosphorylation affects binding of catecholamines to the catalytically inactive
      ferric form of the tyrosine hydroxylase.

PMID- 9636041
TI  - A null lesion in the rhodopin 3,4-desaturase of Rhodospirillum rubrum unmasks a
      cryptic branch of the carotenoid biosynthetic pathway.
AB  - The carotenoids accumulated by a mutant Rhodospirillum rubrum ST4, containing a
      single Tn5 lesion in the pathway for carotenoid biosynthesis, were analyzed by
      HPLC, 1H NMR spectroscopy, and field desorption mass spectrometry. The main
      carotenoid was identified as 3,4,3',4'-tetrahydrospirilloxanthin, and the four
      minor carotenoids were identified as rhodopin, 3,4-dihydroanhydrorhodovibrin, 3',
      4'-dihydrorhodovibrin, and 1,1'-dihydroxylycopene. The C-3,4 and C-3',4' bonds of
      all 5 carotenoids are saturated, and they have 11 conjugated double bonds. With
      the exception of rhodopin, which is a normal intermediate of the wild-type
      pathway, all of the carotenoids are not naturally occurring. The Tn5 lesion was
      assigned to rhodopin 3,4-desaturase which is proposed to catalyze dehydrogenation
      at both ends of the symmetrical spirilloxanthin derivative. An unexpected finding
      was that the enzymes following rhodopin 3,4-desaturase are still able to end
      modify the 3,4-, and 3',4'-saturated precursors and that the order of methylation
      and hydroxylation is not obligatory. It is proposed that the observed nonnatural
      carotenoids can be explained by the inclusion of a cryptic branch, unmasked by
      the absence of rhodopin 3,4-desaturase, in the established linear pathway for
      spirilloxanthin biosynthesis. This is the first example of latent branching of
      the carotenoid biosynthesis pathway exhibited by a carotenoid mutant of a
      phototrophic bacterium.

PMID- 9636042
TI  - Effect of near-infrared light on the S2-state of the manganese complex of
      photosystem II from Synechococcus elongatus.
AB  - The Mn cluster of Photosystem II (PSII) from Synechococcus elongatus was studied
      using EPR. A signal with features between g = 5 and g = 9 is reported from the S2
      state. The signal is attributed to the manganese cluster in a state with a spin
      5/2 state. Spectral simulations of the signal indicate zero field splitting
      parameters where the |E/D| was 0.13. The new signal is formed by irradiating PSII
      samples which contain the spin = 1/2 S2-state using 813 nm light below 200 K.
      This effect is attributed to a spin-state change in the manganese cluster due to
      absorption of the IR light by the Mn-cluster itself. The signal is similar to
      that reported recently in PSII of plants [Boussac, A., Un, S., Horner, O., and
      Rutherford, A. W. (1998) Biochemistry 37, 4001-4007]. In plant PSII the
      comparable signal is formed at a lower temperature (optimally below 77 K), and
      gradual warming of the sample in the dark leads to the formation of the state
      responsible for the well-known g = 4.1 signal prior to formation of the spin 1/2
      multiline signal. In the present work using cyanobacterial PSII, warming of the
      sample in the dark leads to the formation of the spin 1/2 multiline signal
      without formation of the g = 4 type signal as an intermediate. These observations
      provide a partial explanation for the long-standing "mystery of the missing g = 4
      state" in cyanobacterial PSII. The observations are rationalized in terms of
      three possible states which can exist for S2: (i) the spin 1/2 multiline signal,
      (ii) the state responsible for the g = 4.1 signal, and (iii) the new spin 5/2
      state. The relative stability of these states differs between plants and
      cyanobacteria.

PMID- 9636043
TI  - The 18 kDa cytochrome c553 from Heliobacterium gestii: gene sequence and
      characterization of the mature protein.
AB  - The 18 kDa cytochrome c553 is the dominant c-type cytochrome in cell membranes of
      Heliobacterium gestii. After solubilization, this cytochrome was purified in
      three steps as a complex with two other proteins of 32 and 42 kDa. The redox
      midpoint potential of the cytochrome c553 was determined to be +215 mV. The EPR
      spectra clearly show the presence of an ascorbate-reducible low-spin heme with gz
      = 3.048 and gy = 2.238. The gx = trough could not be detected. In addition, a
      Cu(II) signal with g = 2.058 was observed, indicating that one component of the
      cytochrome c553 complex contains a bound copper ion. The gene for the 18 kDa
      cytochrome c553, cyhA, consists of 429 bp coding for a protein of 142 amino
      acids. The association of the cytochrome with the cytoplasmic membrane is
      mediated by two fatty acid molecules, one palmitate and one stearate, that could
      be identified by mass spectrometry. Both fatty acids are most likely bound to the
      cysteine residue of the N-terminally processed protein via a glycerol moiety. The
      amino acid sequence deduced from the DNA sequence exhibits partial identity to
      the membrane-bound cytochrome c551 from Bacillus PS3 [Fujiwara, Y., Oka, M.,
      Hamamoto, T., and Sone, N. (1993) Biochem. Biophys. Res. Commun. 1144, 213-219]
      and to the cytochrome c subunit (NorC) of the nitrous reductase from Pseudomonas
      stutzeri [Zumft, W. G., Braun, C., and Cuypers, H. (1994) Eur. J. Biochem. 219,
      481-490].

PMID- 9636044
TI  - Monitoring the role of oxalate in manganese peroxidase.
AB  - The water proton relaxation rate measurements between 0.01 and 50 MHz on water
      solutions containing the cyanide adduct of the manganese-depleted manganese
      peroxidase (MnP-CN-) and increasing amounts of Mn2+ have been determined. The
      proton relaxivity curves have shown evidence of the formation of the protein/Mn2+
      complex and have been analyzed in order to obtain spin Hamiltonian parameters and
      correlation times. Oxalate is shown not to alter the above profiles. This
      suggests that no protein-Mn2+-oxalate ternary complex is formed and that oxalate
      does not remove Mn2+ from the protein. On the basis of high-resolution 1H NMR
      experiments, we propose that Ce3+ and Gd3+ bind at the manganese site, and, on
      the basis of the charge, we propose that they may mimic Mn3+. The water proton
      relaxation rates of water solutions containing manganese-depleted MnP-CN- and
      increasing amounts of Gd3+ have been measured and analyzed. Oxalate is shown to
      remove the trivalent metal ions. This suggests that trivalent metal ions bind
      oxalate and diffuse away from the protein presumably as oxalate complexes.
      Implications for the enzymatic mechanism are discussed.

PMID- 9636045
TI  - Ligand-induced conformational change in the ferric enterobactin receptor FepA as
      studied by site-directed spin labeling and time-domain ESR.
AB  - A mutant of the ferric enterobactin receptor, FepA, containing a valine to
      cysteine (V338C) substitution was made and the purified protein selectively
      modified with a sulfhydryl-specific nitroxide spin label. In reconstituted
      liposomes, interaction of the attached spin label with a combination of water
      soluble and lipid-soluble relaxation agents indicated that the V338C site was
      located in the polar headgroup region of the membrane, approximately 1.5-4.5 A
      above the phosphate groups of the lipids. Binding of the ligand, ferric
      enterobactin (FeEnt), to the purified spin-labeled protein produced a significant
      decrease in both the rotational freedom and accessibility of the nitroxide,
      indicating the formation of new structural contacts between the spin label and
      either the protein or the bound ligand. Electron spin-echo (ESE) measurements of
      the nitroxide phase-memory relaxation rate in the presence and absence of bound
      ligand showed substantial dipolar coupling between the Fe3+ of FeEnt and the spin
      label and provided an iron-nitroxide distance estimate in the range of 20-30 A.
      We conclude that the ligand-induced changes in spin label motion and
      accessibility are due to new tertiary contacts with the protein and not to direct
      contact with the ligand. These studies suggest that V338C may occupy a hinge
      region connecting the ligand binding surface loop to the beta-barrel and provide
      the strongest evidence to date of an in vitro ligand-induced conformational
      change in FepA.

PMID- 9636046
TI  - Novel branched nod factor structure results from alpha-(1-->3) fucosyl
      transferase activity: the major lipo-chitin oligosaccharides from Mesorhizobium
      loti strain NZP2213 bear an alpha-(1-->3) fucosyl substituent on a nonterminal
      backbone residue.
AB  - Mesorhizobium loti has been described as a microsymbiont of plants of the genus
      Lotus. Lipo-chitin oligosaccharides (LCOs), or Nod factors, produced by several
      representative M. loti strains all have similar structures. Using fast-atom
      bombardment tandem mass spectrometry and NMR spectroscopy, we have now examined
      the LCOs from the type strain NZP2213 and observed a much greater variety of
      structures than has been described for the strains of M.loti studied previously.
      Interestingly, we have identified as the major LCO a structure that bears a
      fucose residue alpha-1,3-linked to the GlcNAc residue proximal to the nonreducing
      terminal GlcNAc residue. This is the first time, to our knowledge, that
      substitution on an internal GlcNAc residue of the LCO backbone has been observed.
      This novel LCO structure suggests the presence of a novel fucosyltransferase
      activity in strain NZP2213. Since the presence of this extra structure does not
      have the effect of broadening the host range, we suggest that the modification of
      the LCOs with a fucose residue linked to a nonterminal GlcNAc residue might
      provide protection against degradation by a particular host plant enzyme (e.g., a
      chitinase) or alternatively represents adaptation to a particular host-specific
      receptor. The action of the alpha-(1-->3) fucosyltransferase seems to reduce
      significantly the activity of NodS, the methyltransferase involved in the
      addition of the N-methyl substituent to the nonreducing terminal GlcNAc residue.
      An additional novel LCO structure has been identified having only a GlcNAc2
      backbone. This is to our knowledge the first description of such a minimal LCO
      structure.

PMID- 9636047
TI  - Glutamate-459 is important for Escherichia coli branching enzyme activity.
AB  - The branching enzyme belongs to the amylolytic family, a group of enzymes that
      cleave and/or transfer chains of glucan. The amylolytic enzymes are homologous
      and all contain four conserved regions, proposed to contain the active site. By
      primary structure analysis, a conserved position unique to branching enzymes has
      been identified. This residue, which is either Asp or Glu, depending on the
      species, is located immediately after the putative catalytic Glu-458 (Escherichia
      coli numbering). Branching enzymes differ from other amylolytic enzymes in having
      this acid pair, and we asked if this motif could be essential for branching
      enzyme action. We used site-directed mutagenesis of the Glu-459 residue in the E.
      coli branching enzyme in order to determine the significance of the conserved
      Asp/Glu in branching enzymes. A substitution of Glu-459 to Asp resulted in
      increased specific activity compared to wild-type, suggesting that the mutation
      had created a more efficient enzyme. Changing Glu-459 to Ala, Lys, or Gln lowered
      the specific activities and altered the preferred substrate from amylose to
      amylopectin.

PMID- 9636048
TI  - Aspartate 221 of thymidylate synthase is involved in folate cofactor binding and
      in catalysis.
AB  - Structural studies indicate that Asp 221 of Lactobacilluscasei thymidylate
      synthase forms a hydrogen bond network with the 2-amino and 3-imino groups of the
      folate [Matthews, D. A. (1990) J. Mol. Biol. 214, 937-948; Finer-Moore, J. S.
      (1990)Biochemistry 29, 6977-6986] that has been proposed to participate in
      catalysis. We prepared a complete replacement set of 19 mutants at position 221
      of L. casei thymidylate synthase. Of these, the only one with sufficient activity
      to complement growth of a thymidylate synthase-deficient host was the Cys mutant.
      To further elucidate the function of the Asp 221 side chain, seven thymidylate
      synthase 221 mutants were studied in detail with regard to catalysis of dTMP
      formation and of thymidylate synthase partial reactions. Most of the mutants
      bound the nucleotide substrate dUMP with only moderate loss of binding affinity,
      indicating that the Asp side chain does not contribute to dUMP binding. Most of
      the mutants catalyzed the cofactor-independent dehalogenation of 5-bromodUMP;
      hence, the Asp side chain of TS is not essential for addition of the catalytic
      Cys residue to the nucleotide substrate. Mutants showed decreased affinity for
      the folate cofactor, but those with side chains capable of hydrogen bond
      formation were less severely affected. Some of the mutants were capable of
      forming covalent thymidylate synthase-5-fluorodUMP-methylenetetrahydrofolate
      complex; hence, the Asp side chain is not essential for steps leading to the
      covalent complex. We conclude that the hydrogen bond network between Asp 221 and
      the folate cofactor contributes to cofactor binding and a catalytic step after
      formation of the covalent ternary complex intermediate.

PMID- 9636049
TI  - Nucleotide and nucleoside analogues as inhibitors of cytosolic 5'-nucleotidase I
      from heart.
AB  - Substrate and product specificity studies were used to develop inhibitors of the
      cytosolic 5'-nucleotidase I (c-N-I) from myocardium. As measured by Vmax/Km, c-N
      I preferred pyrimidine 2'-deoxyribonucleotides as substrates with thymidine
      monophosphate (TMP) being the most efficient. In product inhibition studies,
      thymidine inhibited noncompetitively and inorganic phosphate inhibited
      competitively, consistent with an ordered release of nucleoside prior to
      phosphate. Mirroring nucleotide substrate specificities, pyrimidine nucleosides
      were more potent product inhibitors than purine nucleosides. Thus, pyrimidine
      nucleotide and nucleoside analogues were developed as inhibitors. Phosphonate
      analogues of TMP were synthesized by a novel method. The most potent was the 5'
      phosphonate of 3'-deoxythymidine (ddT) (apparent Ki value of 63 nM). In addition,
      pyrimidine nucleoside analogues were inhibitors with 5-ethynyl-2',3'
      dideoxyuridine being the most potent (apparent Ki value of 3.7 microM). The most
      potent nucleotide and nucleoside inhibitor were both greater than 1000-fold more
      potent inhibiting c-N-I than the cytosolic 5'-nucleotidase II. The nucleoside
      analogue was also greater than 1000-fold more potent against c-N-I than the
      membrane ecto-5'-nucleotidase (e-N). Because the phosphonate analogues measurably
      inhibited e-N (apparent Ki values of 6-12 microM), the selectivity of the
      phosphonates for c-N-I versus e-N was less (40-200-fold). Because of the high
      selectivity for c-N-I versus both of the other 5'-nucleotidases, the nucleoside
      inhibitors of c-N-I may be useful biochemical tools in discerning the role that c
      N-I plays in generating adenosine within myocardium.

PMID- 9636050
TI  - Thermodynamics of a transition state analogue inhibitor binding to Escherichia
      coli chorismate mutase: probing the charge state of an active site residue and
      its role in inhibitor binding and catalysis.
AB  - Electrostatic interactions play important roles in the catalysis of chorismate to
      prephenate by chorismate mutase. Mutation of Gln88 to glutamate in the
      monofunctional chorismate mutase from Escherichia coli results in an enzyme with
      a pH profile of activity significantly different from that of the wild type
      protein. To investigate whether the mutation alters the substrate binding process
      or the catalysis, we have directly determined the thermodynamic parameters of a
      transition state analogue inhibitor binding to the wild-type chorismate mutase
      and its Q88E mutant using isothermal titration calorimetry. The results
      demonstrate that solvent reorganization and hydrophobic interactions contribute
      the predominant free energy to inhibitor binding. The charge state of Glu88 in
      the Q88E mutant was experimentally determined and was shown to be protonated at
      pH 4.5 and ionized at pH 7.8, consistent with earlier hypotheses. Most
      surprisingly, inhibitor binding energetics do not exhibit significant pH
      dependency for both enzymes. Our findings indicate that the charge state of Glu88
      has a small impact on inhibitor binding but plays an important role in the
      catalytic process.

PMID- 9636051
TI  - Flanking proline residues identify the L-type Ca2+ channel binding site of
      calciseptine and FS2.
AB  - Calciseptine and FS2 are 60-amino acid polypeptides, isolated from venom of the
      black mamba (Dendroaspis polylepis polylepis), that block voltage-dependent L
      type Ca2+ channels. We predicted that these polypeptides contain an identical
      functional site between residues 43 and 46 by searching for proline residues that
      mark the flanks of protein-protein interaction sites [Kini, R. M., and Evans, H.
      J. (1966) FEBS Lett. 385, 81-86]. The predicted Ca2+ channel binding site also
      occurs in closely related toxins, C10S2C2 and S4C8. Therefore, it is likely that
      these toxins also will block L-type Ca2+ channels. To test the proposed binding
      site on calciseptine and FS2, an eight-residue peptide, named L-calchin (L-type
      calcium channel inhibitor), was synthesized and examined for biological activity.
      As expected for an L-type Ca2+ channel blocker, L-calchin reduced peak systolic
      and developed pressure in isolated rat heart Langendorff preparations without
      affecting diastolic pressure or heart rate. Furthermore, L-calchin caused a
      voltage-independent block of L-type Ca2+ channel currents in whole-cell patch
      clamped rabbit ventricular myocytes. Thus the synthetic peptide exhibits the L
      type Ca2+ channel blocking properties of the parent molecules, calciseptine and
      FS2, but with a lower potency. These results strongly support the identification
      of a site in calciseptine and FS2 that is important for binding to L-type Ca2+
      channels and reinforce the importance of proline brackets flanking protein
      protein interaction sites.

PMID- 9636052
TI  - Purification, G protein activation, and partial amino acid sequence of a novel
      phospholipase C from squid photoreceptors.
AB  - Invertebrate visual signal transduction is initiated by rhodopsin activation of a
      guanine nucleotide binding protein, Gq, which stimulates phospholipase C (PLC)
      activity. We have previously purified a 140-kDa PLC enzyme from squid
      photoreceptors that is regulated by squid Gq. In these studies, an additional PLC
      enzyme was purified from the cytosol of squid photoreceptors and identified as a
      70-kDa protein by SDS-polyacrylamide gel electrophoresis. Hydrolysis of
      phosphatidylinositol 4,5-bisphosphate (PIP2) by PLC-70 was optimal at pH 5 in the
      presence of 100 microM Ca2+ with a specific activity of 10.3 micromol min-1 mg-1.
      A polyclonal antibody raised against purified PLC-70 did not recognize purified
      PLC-140, and proteolytic digestion of the two purified enzymes with trypsin or
      Staphylococcus aureaus V8 protease showed distinct patterns of peptide fragments,
      indicating that PLC-70 is not a fragment of PLC-140. The partial amino acid
      sequence of the protein showed homology with PLC21 and norpA isozymes cloned from
      Drosophila, and mammalian PLC beta isozymes. Reconstitution of purified GTPgammaS
      bound soluble squid Gq with PLC-70 resulted in significant enhancement of PIP2
      hydrolysis over a range of Ca2+ concentrations and shifted the maximum activation
      by calcium to 1 microM. These results suggest that cephalopod phototransduction
      is mediated by Gq activation of more than one cytosolic PLC enzyme.

PMID- 9636053
TI  - Mutations in the nucleotide-binding sites of P-glycoprotein that affect substrate
      specificity modulate substrate-induced adenosine triphosphatase activity.
AB  - The amino- and carboxy-terminal nucleotide-binding domains (NBD1 and NBD2) of P
      glycoprotein (P-gp) share over 80% sequence identity. Almost all of NBD1 can be
      exchanged by corresponding NBD2 segments with no significant loss of function,
      except for a small segment around the Walker B motif. Within this segment, we
      identified two sets of residues [ERGA --> DKGT (522-525) and T578C] that, when
      replaced by their NBD2 counterparts, cause dramatic alterations of the substrate
      specificity of the protein [Beaudet, L., and Gros, P. (1995) J. Biol. Chem. 270,
      17159-17170]. We wished to gain insight into the molecular basis of this defect.
      For this, we overexpressed the wild-type mouse Mdr3 and variants bearing single
      or double mutations at these positions in the yeast Pichia pastoris. P-gp
      specific ATPase activity was measured in yeast plasma membrane preparations after
      detergent solubilization and reconstitution in Escherichia coli proteoliposomes.
      P-gp proteoliposomes from P. pastoris showed a strong verapamil- and valinomycin
      stimulated ATPase activity, with characteristics (KM, Vmax) similar to those
      measured in mammalian cells. Mutations did not appear to affect the KM for
      Mg2+ATP ( approximately 0.4 mM), but maximum velocity (Vmax) of the drug
      stimulated ATPase activity was severely affected in a substrate/modulator
      specific fashion. Indeed, all mutants showed complete loss of verapamil-induced
      ATPase, while all retained at least some degree of valinomycin-induced ATPase
      activity. Photolabeling studies with [125I]iodoarylazidoprazosin, including
      competition with MDR drugs and modulators, suggested that drug binding was not
      affected in the mutants. The altered drug resistance profiles of the ERGA -->
      DKGT(522-525) and T578C mutants in vivo, together with the observed alterations
      in substrate-induced ATPase activity of these proteins, suggest that the residues
      involved may form part of a signal pathway between the membrane regions
      (substrate binding) and the ATP binding sites.

PMID- 9636054
TI  - Probing the "two-pronged plug two-holed socket" model for the mechanism of
      binding of the Src SH2 domain to phosphotyrosyl peptides: a thermodynamic study.
AB  - Src homology 2 (SH2) domains are protein modules that specifically bind to
      tyrosyl phosphorylated peptides on signaling proteins. X-ray crystallographic
      studies of the SH2 domain of the Src kinase have probed the mechanism of binding,
      leading to the "two-pronged plug two-holed socket" mechanism whereby binding is
      hypothesized to resemble a two-pronged plug (the peptide) inserting into a two
      holed socket (the SH2 domain). This binding model predicts (1) a hydrophobic
      basis for high-affinity binding largely determined by the level of insertion of
      the third residue C-terminal to the phosphotyrosine in the peptide into a
      primarily hydrophobic pocket (the +3 binding pocket) of the SH2 domain, and (2) a
      binding mechanism involving no significant conformational changes in the SH2
      domain. In this study, we have probed these predictions by using isothermal
      titration calorimetry to extract complete thermodynamic profiles (Delta G
      degrees, Delta H degrees, Delta S degrees, Delta Cp degrees) for the binding of
      the Src SH2 domain to two series of tyrosyl phosphopeptides. One series consisted
      of peptides that have been determined by X-ray crystallography to have different
      levels of insertion of the peptide's +3 position into the +3 binding pocket. The
      other series consisted of peptides with progressively smaller hydrophobic side
      chains (I, L, V, and A) at the +3 position. Consistent with a binding mechanism
      that does not involve substantial conformational changes, the Delta Cp degrees
      values for all peptides were small and, at least for the high-affinity
      interactions, similar to the Delta Cp degrees values predicted from surface area
      calculations. However, unexpectedly, this study reveals that high-affinity
      binding was only partially determined by the interactions between the +3 residue
      in the peptide and the +3 binding pocket. Furthermore, the Delta Cp degrees
      values for all peptides studied were similar, implying similar degrees of
      desolvation of the +3 binding pocket upon binding. These results indicate that
      the "two-pronged plug two-holed socket" model is an oversimplification of the Src
      SH2 domain binding mechanism.

PMID- 9636055
TI  - Calcium binding properties of an epidermal growth factor-like domain from human
      thrombomodulin.
AB  - Two different disulfide-paired isomers of the peptide
      T422DIDECENG430GFCSGVCHNL440PGTFECISG449, spanning the junction between the fifth
      and sixth EGF-like domains plus the N-terminal part of the sixth EGF-like domain
      from human thrombomodulin (TM), and containing a consensus calcium binding
      sequence, were synthesized and studied by two-dimensional proton NMR
      spectroscopy. In the course of air oxidation of the fully reduced form of the
      peptide, only uncrossed non EGF-like [1-2, 3-4] disulfide-bonded isomer was
      produced, regardless of the presence of redox buffer and/or calcium. The crossed
      [1-3, 2-4] isomer was prepared from a peptide with acetamidomethyl-protected
      second and fourth cysteines. The isomer with the crossed disulfide pairing was a
      better thrombin inhibitor and was more strongly affected by calcium binding than
      the uncrossed [1-2, 3-4] isomer. Calcium-induced NMR resonance shifts observed
      for the [1-3, 2-4] isomer provide evidence for the presence of a specific calcium
      binding site in the corresponding TM region. There was a limited dispersion of
      the proton chemical shifts and a general lack of nonsequential NOE's for both
      peptide isomers in the presence or absence of calcium. Therefore, neither the apo
      nor the calcium-bound forms of the peptides adopted a completely folded
      conformation, despite the fact that the [1-3, 2-4] isomer contains a potential
      folding nucleus existing in a number of disulfide-rich proteins. Apparently,
      other interactions have to be involved to determine the three-dimensional
      structure of the criss-cross fold in this peptide, most likely the interaction
      with the C-terminal parts of the fifth and/or sixth EGF-like domains.

PMID- 9636056
TI  - Interconversion of the ligand arrays in the CD and EF sites of oncomodulin.
      Influence on Ca2+-binding affinity.
AB  - The parvalbumin metal ion-binding sites differ at the +z and -x residues: Whereas
      the CD site employs serine and glutamate (or aspartate), respectively, the EF
      site employs aspartate and glycine. Although frequently indistinguishable in Ca2+
      and Mg2+-binding assays, the CD and EF sites nonetheless exhibit markedly
      different preferences for members of the lanthanide series [Williams et al.
      (1984) J. Am. Chem. Soc. 106, 5698-5702], underscoring an intrinsic
      nonequivalence. This nonequivalence reaches its pinnacle in the mammalian beta
      parvalbumin (oncomodulin). Whereas the oncomodulin EF site exhibits the expected
      Ca2+/Mg2+ signature, the Ca2+ affinity of the CD site is severely attenuated. To
      obtain insight into the structural factors responsible for this reduction in
      binding affinity, oncomodulin variants were examined in which the CD and EF site
      ligand arrays had been exchanged. Our data suggest that binding affinity may be
      dictated either by ligand identity or by the binding site environment. For
      example, the Ca2+ affinity of the quasi-EF site resulting from the combined S55D
      and D59G mutations is substantially lower than that of the authentic EF site.
      This finding implies that other local environmental variables (e.g., binding loop
      flexibility, electrostatic potentials) within the CD binding site supersede the
      influence of ligand identity. However, the CD site ligand array does not acquire
      a high-affinity signature when imported into the EF site, as in the D94S/G98D
      variant. Instead, it retains its Ca2+-specific signature, implying that this
      constellation of ligands is less sensitive to placement within the protein
      molecule. The D59G and D94S single mutations substantially lower binding
      affinity, consistent with removal of a liganding carboxylate. By contrast, the
      S55D and G98D mutations substantially increase binding affinity, a finding at
      odds with corresponding data collected on model peptide systems. Significantly,
      the Ca2+ affinity of the oncomodulin CD site is increased by mutations that
      weaken binding at the EF site, indicating a negatively cooperative interaction
      between the two sites.

PMID- 9636057
TI  - Fibrinolysis with des-kringle derivatives of plasmin and its modulation by plasma
      protease inhibitors.
AB  - Quantitative characterization of the interaction of des-kringle1-5-plasmin
      (microplasmin) with fibrin(ogen) and plasma protease inhibitors may serve as a
      tool for further evaluation of the role of kringle domains in the regulation of
      fibrinolysis. Comparison of fibrin(ogen) degradation products yielded by plasmin,
      miniplasmin (des-kringle1-4-plasmin), microplasmin, and trypsin on SDS gel
      electrophoresis indicates that the differences in the enzyme structure result in
      different rates of product formation, whereas the products of the four proteases
      are very similar in molecular weight. Kinetic parameters show that plasmin is the
      most efficient enzyme in fibrinogen degradation, and the kcat/KM ratio decreases
      in parallel with the loss of the kringle domains. The catalytic sites of the four
      proteases have similar affinities for fibrin (KM values between 0.12 and 0.21
      microM). Trypsin has the highest catalytic constant for fibrin digestion (kcat =
      0.47 s-1), and among plasmins with different kringle structures, the loss of
      kringle5 results in a markedly lower catalytic rate constant (kcat = 0.0076 s-1
      for microplasmin vs 0.048 s-1 for miniplasmin and 0.064 s-1 for plasmin). In
      addition, microplasmin is inactivated by plasmin inhibitor (k" = 3.9 x 10(5) M-1
      s-1) and antithrombin (k" = 1.4 x 10(3) M-1 s-1) and the rate of inactivation
      decreases in the presence of fibrin(ogen). Heparin (250 nM) accelerates the
      inactivation of microplasmin by antithrombin (k" = 10.5 x 10(3) M-1 s-1 ),
      whereas that by plasmin inhibitor is not affected (k" = 4.2 x 10(5) M-1 s-1).

PMID- 9636058
TI  - Calorimetric investigation of ethidium and netropsin binding to chicken
      erythrocyte chromatin.
AB  - We have investigated the thermodynamic aspects of the ligand binding to
      chromatin, using isothermal titration calorimetry. Two classical DNA ligands were
      used: an intercalator, ethidium bromide, and a minor groove binder, netropsin.
      Stoichiometry, affinity constant, and thermodynamic parameters were determined at
      various salt concentrations and different temperatures. The effect of ionic
      strength was analyzed according to the Record theory applied to chromatin. We
      also compared the binding parameters on naked DNA, H1/H5-depleted chromatin, and
      chromatin. We demonstrated that the presence of histones on DNA still allows the
      ligand binding that takes place according to a simple one single-site model. For
      both ligand types, the thermodynamic driving force is enthalpic and the
      association is characterized by a somewhat weaker affinity and more scattered
      ligand distribution than on naked DNA. The ligand affinity is weakly altered by
      the salt-induced compaction of the chromatin and the binding is accompanied by a
      release of one counterion per ligand molecule. The temperature-dependent studies
      revealed the existence of a small heat capacity change associated with ligand
      binding to chromatin, together with an enthalpy-entropy compensation that
      maintains the free energy constant over the investigated temperature range.

PMID- 9636059
TI  - Sequence context profoundly influences the mutagenic potency of trans-opened
      benzo[a]pyrene 7,8-diol 9,10-epoxide-purine nucleoside adducts in site-specific
      mutation studies.
AB  - The postoligomerization method was used to prepare oligonucleotide 16-mers that
      contained dAdo or dGuo adducts, derived from trans opening of each enantiomer of
      the two diastereomeric benzo[a]pyrene 7,8-diol 9,10-epoxides, in two sequence
      contexts. These 16 oligonucleotides, along with the four corresponding
      oligonucleotides containing unsubstituted purines, were ligated into single
      stranded DNA from bacteriophage M13mp7L2 and transfected into Escherichia coli
      SMH77. The mutagenic effects of replication past these adducts were then
      evaluated. The various adduct isomers induced point mutations at different
      frequencies and with different distributions of mutation types, as was
      anticipated. However, sequence context had the most substantial effects on
      mutation frequency. A high frequency of deletions of a single guanine was found
      in a context where the dGuo adduct was at the 3'-end of a run of five guanines,
      whereas no single base deletion was found in the other context studied, 5'-CGA
      3'. Mutation frequencies in constructs containing dAdo adducts were much higher
      in a 5'-TAG-3' context (37-58%, depending on the individual isomer) than in a 5'
      GAT-3' context (5-20%), and for a given adduct, mutation frequency was up to 10
      fold higher in the former sequence than in the latter. These findings indicate
      that sequence context effects need more thorough evaluation if the goal of
      understanding the mechanism through which DNA adducts lead to mutation is to be
      achieved.

PMID- 9636060
TI  - Rh(phen)2phi3+ as a shape-selective probe of triple helices.
AB  - RNA pur*pur-pyr and pyr*pur-pyr (pur = purine, pyr = pyrimidine) triple helices
      consisting of a Watson-Crick base-paired 28mer hairpin duplex and a Hoogsteen
      base-paired purine or pyrimidine 12mer are targeted with photoactivated cleavage
      by the metal complex Rh(phen)2phi3+ (phen = phenanthroline, phi = 9, 10
      phenanthrenequinone diimine). The metal complex interacts with these triple
      helices in a structure-specific manner. Different cleavage patterns are seen with
      the pyr*pur-pyr and pur*pur-pyr motifs. Cleavage is seen on both of the Watson
      Crick strands of the former motif and primarily on the purine Watson-Crick strand
      of the latter motif. Little cleavage is seen on the Hoogsteen strand for either
      motif. Importantly, the metal complex shows no detectable cleavage on the A-form
      RNA duplex in the absence of the third Hoogsteen strand. The cleavage patterns
      are consistent with an intercalated model for the metal complex in the triple
      helix. Similar cleavage is seen on DNA triple helices, but over a background of
      duplex cleavage. Targeting of synthetic RNA triple helices, but not duplex
      regions, by Rh(phen)2phi3+ provides a basis for the chemical probing of triply
      bonded sites in folded RNA molecules.

PMID- 9636061
TI  - Multiple kinetic intermediates accumulate during the unfolding of horse
      cytochrome c in the oxidized state.
AB  - The unfolding kinetics of horse cytochrome c in the oxidized state has been
      studied at 10, 22, and 34 degreesC as a function of guanidine hydrochloride
      (GdnHCl) concentration. Rapid (millisecond) measurements of far-UV circular
      dichroism (CD) as well as fluorescence quenching due to tryptophan to heme
      excitation energy transfer have been used to monitor the unfolding process. At 10
      degreesC, the decrease in far-UV CD signal that accompanies unfolding occurs in
      two phases. The unobservable burst phase is complete within 4 ms, while the
      slower phase occurs over tens to hundreds of milliseconds. The burst phase
      unfolding amplitude increases cooperatively with an increase in GdnHCl
      concentration, exhibiting a transition midpoint of 3.2 M at 10 degreesC. In
      contrast, no burst phase change in fluorescence occurs during unfolding at 10
      degreesC. At 22 and 34 degreesC, both the fluorescence-monitored unfolding
      kinetics and the far-UV CD-monitored unfolding kinetics are biphasic. At both
      temperatures, the two probes yield burst phase unfolding transitions that are
      noncoincident with respect to the transition midpoints as well as the dependency
      of the burst phase amplitudes on GdnHCl concentration. The results suggest that
      at least two kinetic unfolding intermediates accumulate during unfolding. One
      burst phase intermediate, IU1, has lost virtually all the native-state secondary
      structure, while the other burst phase intermediate, IU2, has lost both secondary
      structure and native-like compactness. The presence of kinetic unfolding
      intermediates is also indicated by the nonlinear dependence of the logarithm of
      the apparent unfolding rate constant on GdnHCl concentration, which is
      particularly pronounced at 10 and 22 degreesC. Analysis of the burst phase
      unfolding transitions obtained using the two probes shows that the stabilities of
      IU1 and IU2 decrease steadily with an increase in temperature from 10 to 34
      degreesC, suggesting that the structures present in them are stabilized
      principally by hydrogen bonding interactions.

PMID- 9636062
TI  - Secondary tritium and solvent deuterium isotope effects as a probe of the
      reaction catalyzed by porcine recombinant dihydropyrimidine dehydrogenase.
AB  - Dihydropyrimidine dehydrogenase catalyzes the rate-limiting step in the
      degradation of pyrimidines in mammals, the reduction of uracil or thymine to
      their 5,6-dihydro derivatives. The reduction of uracil by enzyme-bound reduced
      flavin involves both proton and hydride transfer. In order to determine whether
      hydride and proton transfer occur in a concerted or stepwise fashion, and to
      determine the nature of the transition state for the reduction, secondary tritium
      kinetic isotope effects were measured in H2O and D2O. The tritium isotope effect
      using 5-3H-uracil is 0.90 +/- 0.03 in H2O and becomes more inverse, 0.85 +/-
      0.04, in D2O. Data are interpreted in terms of a stepwise reduction at C-6
      followed by protonation at C-5. A late transition state is proposed for the
      proton transfer at C-5 of uracil.

PMID- 9636063
TI  - A reversibly unfolding fragment of P22 tailspike protein with native structure:
      the isolated beta-helix domain.
AB  - The homotrimeric tailspike endorhamnosidase of phage P22 has been used to compare
      in vivo and in vitro folding pathways and the influence of single amino acid
      substitutions thereon. Its main structural motif, which contains the known
      folding mutation sites, consists of three large right-handed parallel beta
      helices. A thermodynamic analysis of the stability of tailspike is prevented by
      the irreversibility of unfolding at high temperatures or high concentrations of
      denaturant, probably due to interdigitation of the domains neighboring the beta
      helix. We therefore expressed and isolated a tailspike fragment comprising only
      its central beta-helix domain (residues 109-544). As shown by equilibrium
      ultracentrifugation, the isolated beta-helix is a monomer at concentrations below
      1 microM and trimerizes reversibly at higher protein concentrations. Both the
      similarity of fluorescence and CD spectra, compared to the complete protein, and
      the specific binding and hydrolysis of substrate suggest a nativelike structure.
      Moreover, urea denaturation transitions of the beta-helix domain are freely
      reversible, providing the basis for a future quantitative analysis of the effects
      of the folding mutations on the thermodynamic stability of the domain and of
      structural features responsible for folding and stability of the parallel beta
      helix motif in general.

PMID- 9636064
TI  - NMR study of the conformation and localization of porcine galanin in SDS
      micelles. Comparison with an inactive analog and a galanin receptor antagonist.
AB  - Galanin is a 29/30-residue neuro-endocrine peptide which performs its many
      important physiological functions via a membrane-bound receptor. By using two
      dimensional proton NMR spectroscopy, complete relaxation matrix analysis, and
      simulated annealing, the conformation of porcine galanin was determined in a
      membrane-mimicking solvent containing sodium dodecyl sulfate (SDS) micelles. The
      final family of calculated structures displays three well-defined beta- or gamma
      turn regions, comprising residues 1-5, 7-10, and 24-27, but has otherwise a
      random conformation. The receptor-interacting N-terminal part, residues 1-5, was
      found to be best defined with a backbone RMSD value of 0.12 A. The mode of
      association between galanin and the SDS micelle was determined by observing the
      broadening effect on proton resonances, when spin-labeled 5- and 12-doxyl
      stearate molecules were added. It was concluded that galanin is located close to
      the surface of the micelle with two regions, residues 6-9 and 24-29, as well as
      two single residues, 18 and 21, reaching out into the aqueous solvent. Additional
      NMR studies were carried out on an inactive analogue, Ala2-galanin, and an
      antagonist M40. The results show that the proton resonances of galanin and M40
      have identical chemical shifts in the N-terminal receptor-interacting region,
      indicating similar solution structures in this region. For Ala2-galanin, the same
      region displays a spectral heterogeneity with chemical shifts clearly different
      from the other two peptides, indicative of different secondary structures. These
      results may provide a structural background for the antagonist activity of M40
      and the hormonal inactivity of Ala2-galanin, as compared to galanin.

PMID- 9636065
TI  - Folding kinetics of a fluorescent variant of monomeric lambda repressor.
AB  - A tryptophan-containing variant of monomeric lambda repressor has been made, and
      its folding kinetics were analyzed at 20 degreesC using fluorescence stopped-flow
      and dynamic NMR. Equilibrium denaturation curves obtained by circular dichroism,
      fluorescence, and NMR are superimposable. Stopped-flow analysis indicates that in
      the absence of denaturants the folding reaction is complete within the dead-time
      of the experiment. Within higher denaturant conditions, where the folding rate is
      slower, NMR and stopped-flow agree on the folding and unfolding rates of the
      protein. In 3.4 M urea and 1.8 M GdmCl, we show that the variant folds within 2
      ms. Extrapolation indicates that the folding time is 20 micro(s) in the absence
      of denaturants. All folding and unfolding reactions displayed monoexponential
      kinetics, and no burst-phases were observed. In addition, the thermodynamic
      parameters Delta G and meq obtained from the kinetic analysis are consistent with
      the equilibrium experiments. The results support a two-state Dleft and right
      arrow N folding model.

PMID- 9636066
TI  - A semiconserved residue inhibits complex formation by stabilizing interactions in
      the free state of a theophylline-binding RNA.
AB  - The theophylline-binding RNA aptamer contains a 15 nucleotide motif that is
      required for high-affinity ligand binding. One residue within this RNA motif is
      only semiconserved and can be an A or C. This residue, C27, was disordered in the
      previously determined three-dimensional structure of the complex, suggesting that
      it is dynamic in solution. 13C Relaxation measurements are reported here,
      demonstrating that C27 is highly dynamic in the otherwise well-ordered RNA
      theophylline complex. A synthetic complex with an abasic residue at position 27
      was found to exhibit wild-type binding affinity (Kd approximately 0.2 microM),
      indicating that the base of residue 27 is not directly involved with theophylline
      binding. Surprisingly, the U27 and G27 RNAs were found to bind theophylline with
      low affinity (Kd values > 4 microM). NMR spectroscopy on the U27 RNA revealed the
      presence of an A7-U27 base pair in the free RNA that prevents formation of a
      critical base-platform structural motif and therefore blocks theophylline
      binding. Similarly, a protonated A7H+-C27 base pair forms in the absence of
      theophylline at low pH, which explains the unusual pH dependence of theophylline
      binding of the C27 RNA aptamer. Thus the weak binding for various nucleotides at
      position 27 arises not from unfavorable interactions in the RNA-theophylline
      complex but instead from stable interactions in the free state of the RNA that
      inhibit theophylline binding.

PMID- 9636067
TI  - Strong selective pressure to use G:U to mark an RNA acceptor stem for alanine.
AB  - The identity of alanine tRNAs is dependent on a G:U base pair at the 3:70
      position of the acceptor helix. This system of molecular recognition is widely
      distributed from bacteria to human-cell cytoplasm. In contrast, some
      mitochondrial alanine acceptor helices are markedly different and contain
      nucleotides known to block aminoacylation by a nonmitochondrial enzyme. Thus,
      acceptor helix recognition may differ in these systems and may not depend on G:U.
      Here we report an example of a Caenorhabditis elegans mitochondrial system where
      the G:U pair is preserved but where proximal nucleotides known to block charging
      by a nonmitochondrial enzyme are also present. We show that, as expected, the
      mitochondrial substrate is not charged by the bacterial enzyme. In contrast, the
      cloned mitochondrial enzyme charged both mitochondrial and bacterial
      microhelices. Strikingly, charging of each required the G:U pair. Thus, G:U
      recognition persists even with an acceptor helix context that inactivates
      nonmitochondrial systems. The results suggest strong selective pressure to use
      G:U in a variety of contexts to mark an acceptor stem for alanine. Separate
      experiments also demonstrate that, at least for the mitochondrial enzyme, helix
      instability or irregularity is not important for recognition of G:U.

PMID- 9636068
TI  - Secretory phospholipase A2 and lipoprotein lipase enhance 15-lipoxygenase-induced
      enzymic and nonenzymic lipid peroxidation in low-density lipoproteins.
AB  - The oxidation of low-density lipoprotein (LDL) is thought to contribute to
      atherogenesis. 15-Lipoxygenase (15LO) induces LDL oxidation, and phospholipase A2
      enhances this process [Sparrow, C. P. , Parthasarathy, S., and Steinberg, D.
      (1988) J. LipidRes. 29, 745-753]. As the underlying mechanism of the enhancing
      effect has not been investigated previously, we here show that in the presence of
      soybean 15LO (SLO) or human 15LO (rhLO), the addition of lipoprotein lipase,
      porcine pancreatic, or human type IIa secretory phospholipase A2 (sPLA2) greatly
      enhanced the accumulation of hydro(pero)xides of all major classes of LDL's
      lipids. Hydroperoxides of free fatty acids accumulated exclusively as enzymic
      products with kinetics reflecting both the formation of free fatty acids and the
      initial 'build-up' of alpha-tocopheroxyl radical. In contrast, hydroperoxides of
      cholesteryl esters and phosphatidylcholine accumulated linearly over
      comparatively longer periods of time and, in the case of rhLO, well beyond
      inactivation of the oxygenase. With SLO, formation of oxidized esterified lipids
      occurred nonenzymically, independent of the presence of lipase and despite the
      oxygenase remaining active until the end of the incubation. Enhancement of rhLO
      induced LDL lipid peroxidation by sPLA2 was eliminated by a neutralizing anti
      sPLA2 antibody, indicating that lipolytic activity was required for this effect.
      LDL depleted of alpha-tocopherol was resistant to oxidation by 15LO alone,
      whereas lipase overcame this resistance, demonstrating that lipases enhance 15LO
      induced enzymic and nonenzymic peroxidation of LDL lipids. This is likely due to
      provision of free fatty acid substrate, resulting in an enhanced rate of free
      radical formation which itself causes nonenzymic peroxidation of esterified
      lipids. As lipases and 15LO are present in atherosclerotic lesions, our findings
      could be of pathophysiological significance.

PMID- 9636069
TI  - Diminished Sonic hedgehog signaling and lack of floor plate differentiation in
      Gli2 mutant mice.
AB  - Floor plate cells at the midline of the neural tube are specified by high-level
      activity of Sonic hedgehog (Shh) secreted by notochord, whereas motor neurons are
      thought to be specified by a lower level activity of Shh secreted in turn by
      floor plate cells. In Drosophila, the Gli zinc finger protein Cubitus interruptus
      functions as a transcription factor activating Hedgehog-responsive genes. We
      report that the expression of known Shh-responsive genes such as Ptc and Gli1 is
      downregulated in mutant mice lacking Gli2 function. Gli2 mutants fail to develop
      a floor plate yet still develop motor neurons, which occupy the ventral midline
      of the neural tube. Our results imply that Gli2 is required to mediate high level
      but not low level Shh activity and show that the development of motor neurons can
      occur in the absence of floor plate induction.

PMID- 9636070
TI  - The WIGGUM gene is required for proper regulation of floral meristem size in
      Arabidopsis.
AB  - The study of cell division control within developing tissues is central to
      understanding the processes of pattern formation. The floral meristem of
      angiosperms gives rise to floral organs in a particular number and pattern.
      Despite its critical role, little is known about how cell division is controlled
      in the floral meristem, and few genes involved have been identified. We describe
      the phenotypic effects of mutations in WIGGUM, a gene required for control of
      cell proliferation in the floral and apical meristem of Arabidopsis thaliana.
      wiggum flowers contain more organs, especially sepals and petals, than found in
      wild-type flowers. This organ number phenotype correlates with specific size
      changes in the early floral meristem, preceding organ initiation. Genetic studies
      suggest that WIGGUM acts on a similar process but in a separate pathway than the
      CLAVATA1 and CLAVATA3 genes in meristem size regulation, and reveal interactions
      with other genes affecting meristem structure and identity. Analysis of double
      mutant phenotypes also reveals a role for WIGGUM in apical meristem function. We
      propose that WIGGUM plays a role in restricting cell division relative to
      cellular differentiation in specific regions of the apical and floral meristems.

PMID- 9636071
TI  - Pattern formation and growth during floral organogenesis: HUELLENLOS and
      AINTEGUMENTA are required for the formation of the proximal region of the ovule
      primordium in Arabidopsis thaliana.
AB  - Our understanding of the molecular mechanisms that regulate and integrate the
      temporal and spatial control of cell proliferation during organ ontogenesis,
      particularly of floral organs, continues to be primitive. The ovule, the
      progenitor of the seed, of Arabidopsis thaliana has been used to develop an
      effective model system for the analysis of plant organogenesis. A typical feature
      of a generalized ovule is the linear arrangement of at least three distinct
      elements, the funiculus, chalaza and nucellus, along a proximal-distal axis. This
      pattern is supposed to be established during the early proliferative phase of
      ovule development. We provide genetic evidence that the young ovule primordium
      indeed is a composite structure. Two genes, HUELLENLOS and AINTEGUMENTA have
      overlapping functions in the ovule and differentially control the formation of
      the central and proximal elements of the primordium. The results indicate that
      proximal-distal pattern formation in the Arabidopsis ovule takes place in a
      sequential fashion, starting from the distal end. Furthermore, we show that
      HUELLENLOS also regulates the initiation and/or maintenance of integument and
      embryo sac ontogenesis and interestingly prevents inappropriate cell death in the
      young ovule.

PMID- 9636072
TI  - Identification and analysis of a gene that is essential for morphogenesis and
      prespore cell differentiation in Dictyostelium.
AB  - We have identified a gene (PslA) that is expressed throughout Dictyostelium
      development and encodes a novel protein that is required for proper aggregation
      and subsequent cell-type differentiation and morphogenesis. pslA null (pslA-)
      cells produce large aggregation streams under conditions in which wild-type cells
      form discrete aggregates. Tips form along the stream, elongate to produce a
      finger, and eventually form a terminal structure that lacks a true sorus (spore
      head). More than half of the cells remain as a mass at the base of the developing
      fingers. The primary defect in the pslA- strain is the inability to induce
      prespore cell differentiation. Analyses of gene expression show a complete lack
      of prespore-specific gene expression and no mature spores are produced. In
      chimeras with wild-type cells, pslA- cells form the prestalk domain and normal,
      properly proportioned fruiting bodies can be produced. This indicates that pslA-
      cells are able to interact with wild-type cells and regulate patterning, even
      though pslA- cells are unable to express prespore cell-type-specific genes, do
      not participate in prespore cell differentiation and do not produce pslA- spores
      in the chimeras. While pslA- cells produce mature, vacuolated stalk cells during
      multicellular development, pslA- cells are unable to do so in vitro in response
      to exogenous DIF (a morphogen required for prestalk and stalk cell
      differentiation). These results indicate that pslA- cells exhibit a defect in the
      prestalk/stalk cell pathways under these experimental conditions. Our results
      suggest that PslA's primary function is to regulate prespore cell determination
      very early in the prespore pathway via a cell-autonomous mechanism, possibly at
      the time of the initial prestalk/prespore cell-fate decision. Indirect
      immunofluorescence of myc-tagged PslA localizes the protein to the nucleus,
      suggesting that PslA may function to control the prespore pathway at the level of
      transcription.

PMID- 9636073
TI  - A novel Xenopus mix-like gene milk involved in the control of the endomesodermal
      fates.
AB  - Here we describe a novel Xenopus homeobox gene, milk, related by sequence
      homology and expression pattern to the vegetally expressed Mix.1. As is the case
      with Mix.1, milk is an immediate early response gene to the mesoderm inducer
      activin. milk is expressed at the early gastrula stage in the vegetal cells,
      fated to form endoderm, and in the marginal zone fated to form mesoderm. During
      gastrulation, expression of milk becomes progressively reduced in the involuting
      mesodermal cells but is retained in the endoderm, suggesting that it may play a
      key role in the definition of the endo-mesodermal boundary in the embryo.
      Overexpression of milk in the marginal zone blocks mesodermal cell involution,
      represses the expression of several mesodermal genes such as Xbra, goosecoid,
      Xvent-1 or Xpo and increases the expression of the endodermal gene, endodermin.
      In the dorsal marginal zone, overexpression of milk leads to a severe late
      phenotype including the absence of axial structures. Ectopic expression of milk
      in the animal hemisphere or in ectodermal explants induces a strong expression of
      endodermin. Taken together, we propose that milk plays a role in the correct
      patterning of the embryo by repressing mesoderm formation and promoting endoderm
      identity.

PMID- 9636074
TI  - Hoxa-2 restricts the chondrogenic domain and inhibits bone formation during
      development of the branchial area.
AB  - In Hoxa-2(-/- )embryos, the normal skeletal elements of the second branchial arch
      are replaced by a duplicated set of first arch elements. We show here that Hoxa-2
      directs proper skeletal formation in the second arch by preventing chondrogenesis
      and intramembranous ossification. In normal embryos, Hoxa-2 is expressed
      throughout the second arch mesenchyme, but is excluded from the chondrogenic
      condensations. In the absence of Hoxa-2, chondrogenesis is activated ectopically
      within the rostral Hoxa-2 expression domain to form the mutant set of cartilages.
      In Hoxa-2(-/- )embryos the Sox9 expression domain is shifted into the normal Hoxa
      2 domain. Misexpression of Sox9 in this area produces a phenotype resembling that
      of the Hoxa-2 mutants. These results indicate that Hoxa-2 acts at early stages of
      the chondrogenic pathway, upstream of Sox9 induction. We also show that Hoxa-2
      inhibits dermal bone formation when misexpressed in its precursors. Furthermore,
      molecular analyses indicate that Cbfa1 is upregulated in the second branchial
      arches of Hoxa-2 mutant embryos suggesting that prevention of Cbfa1 induction
      might mediate Hoxa-2 inhibition of dermal bone formation during normal second
      arch development. The implications of these results on the patterning of the
      branchial area are discussed.

PMID- 9636075
TI  - Vax1 is a novel homeobox-containing gene expressed in the developing anterior
      ventral forebrain.
AB  - The vertebrate forebrain is formed at the rostral end of the neural plate under
      the regulation of local and specific signals emanating from both the endomesoderm
      and neuroectoderm. The development of the rostral and ventral forebrain in
      particular was difficult to study, mainly because no specific markers are
      available to date. Here, we report the identification of Vax1, a novel homeobox
      containing gene identified in mouse, Xenopus and human. It is closely related to
      members of the Not and Emx gene families, all of which are required for the
      formation of structures where they are expressed. In mouse and Xenopus, Vax1
      expression first occurs in the rostral neural plate, in the medial anterior
      neural ridge and adjacent ectoderm. Later, at midgestation in the mouse and
      tadpole stage in Xenopus, the expression remains confined in the derivatives of
      this territory which differentiate into rostromedial olfactory placode, optic
      nerve and disc, and anterior ventral forebrain. Together, these observations
      suggest that Vax1 could have an early evolutionary origin and could participate
      in the specification and formation of the rostral and ventral forebrain in
      vertebrates. Comparison of the limits of the expression territory of Vax1 with
      that of Dlx1, Pax6 and Emx1 indicates that the corticostriatal ridge is a complex
      structure with distinct identifiable genetic compartments. Besides, the study of
      Vax1 expression in Pax6-deficient homozygous brains indicates that its regulation
      is independent of Pax6, although the expression patterns of these two genes
      appear complementary in wild-type animals. Vax1 chromosomal location is mapped at
      the distal end of the mouse chromosome 19, linked with that of Emx2. These two
      genes may have arisen by tandem duplication. The Vax1 gene is thus an interesting
      new tool to study the rostral ventral forebrain patterning, morphogenesis and
      evolution as well as the terminal differentiation of the forebrain in mouse and
      Xenopus.

PMID- 9636076
TI  - SCL specifies hematopoietic mesoderm in Xenopus embryos.
AB  - Targeted gene disruption experiments in the mouse have demonstrated an absolute
      requirement for several transcription factors for the development of
      hematopoietic progenitors during embryogenesis. Disruption of the basic helix
      loop-helix gene SCL (stem cell leukemia) causes a block early in the
      hematopoietic program with defects in all hematopoietic lineages. To understand
      how SCL participates in the organogenesis of blood, we have isolated cDNAs
      encoding Xenopus SCL and characterized the function of SCL during embryogenesis.
      We demonstrate that SCL is expressed in ventral mesoderm early in embryogenesis.
      SCL expression is induced by BMP-4, and a dominant negative BMP-4 receptor
      inhibits SCL expression in the ventral region of the embryo. Expression of SCL in
      either bFGF-treated animal pole explants or dorsal marginal zone explants leads
      to the expression of globin protein. Furthermore, over-expression of SCL does not
      alter normal dorsal-ventral patterning in the embryo, indicating that SCL acts to
      specify mesoderm to a hematopoietic fate after inductive and patterning events
      have occurred. We propose that SCL is both necessary and sufficient to specify
      hematopoietic mesoderm, and that it has a similar role in specifying
      hematopoietic cell fate as MyoD has in specifying muscle cell fate.

PMID- 9636077
TI  - Role of laminin polymerization at the epithelial mesenchymal interface in
      bronchial myogenesis.
AB  - Undifferentiated mesenchymal cells were isolated from mouse embryonic lungs and
      plated at subconfluent and confluent densities. During the first 5 hours in
      culture, all the cells were negative for smooth muscle markers. After 24 hours in
      culture, the mesenchymal cells that spread synthesized smooth muscle alpha-actin,
      muscle myosin, desmin and SM22 in levels comparable to those of mature smooth
      muscle. The cells that did not spread remained negative for smooth muscle
      markers. SM differentiation was independent of cell-cell contact or
      proliferation. In additional studies, undifferentiated lung mesenchymal cells
      were cocultured with lung embryonic epithelial cells at high density. The
      epithelial cells aggregated into cysts surrounded by mesenchymal cells and a
      basement membrane was formed between the two cell types. In these cocultures, the
      mesenchymal cells in contact with the basement membrane spread and differentiated
      into smooth muscle. The rest of the mesenchymal cells remained round and negative
      for smooth muscle markers. Inhibition of laminin polymerization by an antibody to
      the globular regions of laminin beta1/gamma1 chains blocked basement membrane
      assembly, mesenchymal cell spreading and smooth muscle differentiation. These
      studies indicated that lung embryonic mesenchymal cells have the potential to
      differentiate into smooth muscle and the process is triggered by their spreading
      along the airway basement membrane.

PMID- 9636078
TI  - Two domains in vertebral development: antagonistic regulation by SHH and BMP4
      proteins.
AB  - It has previously been shown that the notochord grafted laterally to the neural
      tube enhances the differentiation of the vertebral cartilage at the expense of
      the derivatives of the dermomyotome. In contrast, the dorsomedial graft of a
      notochord inhibits cartilage differentiation of the dorsal part of the vertebra
      carrying the spinous process. Cartilage differentiation is preceded by the
      expression of transcription factors of the Pax family (Pax1/Pax9) in the
      ventrolateral domain and of the Msx family in the dorsal domain. The
      proliferation and differentiation of Msx-expressing cells in the dorsal
      precartilaginous domain of the vertebra are stimulated by BMP4, which acts
      upstream of Msx genes. It has previously been shown that the SHH protein arising
      from the notochord (and floor plate) is necessary for the survival and further
      development of Pax1/Pax9-expressing sclerotomal cells. We show here that SHH acts
      antagonistically to BMP4. SHH-producing cells grafted dorsally to the neural tube
      at E2 inhibit expression of Bmp4 and Msx genes and also inhibits the
      differentiation of the spinous process. We present a model that accounts for
      cartilage differentiation in the vertebra.

PMID- 9636079
TI  - hermaphrodite and doublesex function both dependently and independently to
      control various aspects of sexual differentiation in Drosophila.
AB  - The hermaphrodite (her) gene is necessary for sexual differentiation in
      Drosophila. Our characterization of her's zygotic function suggests that one set
      of female-specific terminal differentiation genes, the yolk protein (yp) genes,
      is transcriptionally activated by two separate pathways. One is a female-specific
      pathway, which is positively regulated by the female-specific doublesex protein
      (DSXF). The other is a non-sex-specific pathway, that is positively regulated by
      HER. The HER pathway is prevented from functioning in males by the action of the
      male-specific doublesex protein (DSXM). The HER and DSX pathways also function
      independently to control downstream target genes in the precursor cells that give
      rise to the vaginal teeth and dorsal anal plate of females, and the lateral anal
      plates of males. However, a female-specific pathway that is dependent on both
      DSXF and HER controls the female-specific differentiation of the foreleg bristles
      and tergites 5 and 6, and the male-specific differentiation of these tissues does
      not require the suppression of HER's function by DSXM.

PMID- 9636080
TI  - Ecdysone pathway is required for furrow progression in the developing Drosophila
      eye.
AB  - In Drosophila, secretion of the steroid hormone ecdysone from the prothoracic
      ring gland coordinates and triggers events such as molting and metamorphosis. In
      the developing Drosophila compound eye, pattern formation and cell-type
      specification initiate at a moving boundary known as the morphogenetic furrow. We
      have investigated the role of ecdysone in eye development and report here that
      the ecdysone signaling pathway is required for progression of the morphogenetic
      furrow in the eye imaginal disc of Drosophila. Genetic disruption both of the
      ecdysone signal in vivo with the ecdysoneless1 (ecd1) mutant and of ecdysone
      response with a Broad-Complex mutant result in disruption of morphogenetic furrow
      progression. In addition, we show that ecdysone-dependent gene expression, both
      of a reporter of transcriptional activity of the Ecdysone Receptor and of the Z1
      isoform of the Broad Complex, are localized in and close to the furrow. These
      results suggest that, in the morphogenetic furrow, temporal hormonal signals are
      integrated into genetic pathways specifying spatial pattern.

PMID- 9636081
TI  - Transcription factor GATA-4 is expressed in a sexually dimorphic pattern during
      mouse gonadal development and is a potent activator of the Mullerian inhibiting
      substance promoter.
AB  - Mammalian gonadal development and sexual differentiation are complex processes
      that require the coordinated expression of a specific set of genes in a strict
      spatiotemporal manner. Although some of these genes have been identified, the
      molecular pathways, including transcription factors, that are critical for the
      early events of lineage commitment and sexual dimorphism, remain poorly
      understood. GATA-4, a member of the GATA family of transcription factors, is
      present in the gonads and may be a regulator of gonadal gene expression. We have
      analyzed the ontogeny of gonadal GATA-4 expression by immunohistochemistry. GATA
      4 protein was detected as early as embryonic day 11.5 in the primitive gonads of
      both XX and XY mouse embryos. In both sexes, GATA-4 specifically marked the
      developing somatic cell lineages (Sertoli in testis and granulosa in ovary) but
      not primordial germ cells. Interestingly, abundant GATA-4 expression was
      maintained in Sertoli cells throughout embryonic development but was markedly
      down-regulated shortly after the histological differentiation of the ovary on
      embryonic day 13.5. This pattern of expression suggested that GATA-4 might be
      involved in early gonadal development and possibly sexual dimorphism. Consistent
      with this hypothesis, we found that the Mullerian inhibiting substance promoter
      which harbors a conserved GATA element is a downstream target for GATA-4. Thus,
      transcription factor GATA-4 may be a new factor in the cascade of regulators that
      control gonadal development and sex differentiation in mammals.

PMID- 9636082
TI  - Mutant Vg1 ligands disrupt endoderm and mesoderm formation in Xenopus embryos.
AB  - The Xenopus Vg1 gene, a TGFbeta superfamily member, is expressed as a maternal
      mRNA localized to prospective endoderm, and mature Vg1 protein can induce both
      endodermal and mesodermal markers in embryonic cells. Most previous work on
      embryonic inducers, including activin, BMPs and Vg1, has relied on ectopic
      expression to assay for gene function. Here we employ a mutant ligand approach to
      block Vg1 signaling in developing embryos. The results indicate that Vg1
      expression is essential for normal endodermal development and the induction of
      dorsal mesoderm in vivo.

PMID- 9636083
TI  - Frizzled-8 is expressed in the Spemann organizer and plays a role in early
      morphogenesis.
AB  - Wnts are secreted signaling molecules implicated in a large number of
      developmental processes. Frizzled proteins have been identified as likely
      receptors for Wnt ligands in vertebrates and invertebrates, but a functional role
      for vertebrate frizzleds has not yet been defined. To assess the endogenous role
      of frizzled proteins during vertebrate development, we have identified and
      characterized a Xenopus frizzled gene (xfz8). It is highly expressed in the deep
      cells of the Spemann organizer prior to dorsal lip formation and in the early
      involuting marginal zone. Ectopic expression of xfz8 in ventral cells leads to
      complete secondary axis formation and can synergize with Xwnt-8 while an
      inhibitory form of xfz8 (Nxfz8) blocks axis duplication by Xwnt-8, consistent
      with a role for xfz8 in Wnt signal transduction. Expression of Nxfz8 in dorsal
      cells has profound effects on morphogenesis during gastrulation and neurulation
      that result in dramatic shortening of the anterior-posterior axis. Our results
      suggest a role for xfz8 in morphogenesis during the gastrula stage of
      embryogenesis.

PMID- 9636084
TI  - Isolation and developmental expression of the amphioxus Pax-6 gene (AmphiPax-6):
      insights into eye and photoreceptor evolution.
AB  - Pax-6 genes have been identified from a broad range of invertebrate and
      vertebrate animals and shown to be always involved in early eye development.
      Therefore, it has been proposed that the various types of eyes evolved from a
      single eye prototype, by a Pax-6-dependent mechanism. Here we describe the
      characterization of a cephalochordate Pax-6 gene. The single amphioxus Pax-6 gene
      (AmphiPax-6) can produce several alternatively spliced transcripts, resulting in
      proteins with markedly different amino and carboxy termini. The amphioxus Pax-6
      proteins are 92% identical to mammalian Pax-6 proteins in the paired domain and
      100% identical in the homeodomain. Expression of AmphiPax-6 in the anterior
      epidermis of embryos may be related to development of an olfactory epithelium.
      Expression is also detectable in Hatschek's left diverticulum as it forms the
      preoral ciliated pit, part of which gives rise to the homolog of the vertebrate
      anterior pituitary. A zone of expression in the anterior neural plate of early
      embryos is carried into the cerebral vesicle (a probable diencephalic homolog)
      during neurulation. This zone includes cells that will differentiate into the
      lamellar body, a presumed homolog of the vertebrate pineal eye. In neurulae,
      AmphiPax-6 is also expressed in ventral cells at the anterior tip of the nerve
      cord; these cells are precursors of the photoreceptive neurons of the frontal
      eye, the presumed homolog of the vertebrate paired eyes. However, AmphiPax-6
      expression was not detected in two additional types of photoreceptors, the Joseph
      cells or the organs of Hesse, which are evidently relatively recent adaptations
      (ganglionic photoreceptors) and appear to be rare exceptions to the general rule
      that animal photoreceptors develop from a genetic program triggered by Pax-6.

PMID- 9636085
TI  - Mutations in mouse Aristaless-like4 cause Strong's luxoid polydactyly.
AB  - Mutations that affect vertebrate limb development provide insight into pattern
      formation, evolutionary biology and human birth defects. Patterning of the limb
      axes depends on several interacting signaling centers; one of these, the zone of
      polarizing activity (ZPA), comprises a group of mesenchymal cells along the
      posterior aspect of the limb bud that express sonic hedgehog (Shh) and plays a
      key role in patterning the anterior-posterior (AP) axis. The mechanisms by which
      the ZPA and Shh expression are confined to the posterior aspect of the limb bud
      mesenchyme are not well understood. The polydactylous mouse mutant Strong's
      luxoid (lst) exhibits an ectopic anterior ZPA and expression of Shh that results
      in the formation of extra anterior digits. Here we describe a new chlorambucil
      induced deletion allele, lstAlb, that uncovers the lst locus. Integration of the
      lst genetic and physical maps suggested the mouse Aristaless-like4 (Alx4) gene,
      which encodes a paired-type homeodomain protein that plays a role in limb
      patterning, as a strong molecular candidate for the Strong's luxoid gene. In
      genetic crosses, the three lst mutant alleles fail to complement an Alx4 gene
      targeted allele. Molecular and biochemical characterization of the three lst
      alleles reveal mutations of the Alx4 gene that result in loss of function. Alx4
      haploinsufficiency and the importance of strain-specific modifiers leading to
      polydactyly are indicative of a critical threshold requirement for Alx4 in a
      genetic program operating to restrict polarizing activity and Shh expression in
      the anterior mesenchyme of the limb bud, and suggest that mutations in Alx4 may
      also underlie human polydactyly.

PMID- 9636086
TI  - TGF-beta/BMP superfamily members, Gbb-60A and Dpp, cooperate to provide pattern
      information and establish cell identity in the Drosophila wing.
AB  - Within a developing organism, cells receive many signals which control their
      proliferation, fate specification and differentiation. One group of such proteins
      is the TGF-beta/BMP class of related signaling molecules. Based on expression
      studies, multiple members of this class of ligands must impinge upon the same
      cells of a developing tissue; however, the role that multiple TGF-beta/BMP
      ligands may play in directing the development of such a tissue is not understood.
      Here we provide evidence that multiple BMPs are required for growth and
      patterning of the Drosophila wing. The Drosophila BMP gene, gbb-60A, exhibits a
      requirement in wing morphogenesis distinct from that shown previously for dpp, a
      well-characterized Drosophila BMP member. gbb-60A mutants exhibit a loss of
      pattern elements from the wing, particularly those derived from cells in the
      posterior compartment, consistent with the gbb-60A RNA and protein expression
      pattern. Based on genetic analysis and expression studies, we conclude that Gbb
      60A must signal primarily as a homodimer to provide patterning information in the
      wing imaginal disc. We demonstrate that gbb-60A and dpp genetically interact and
      that specific aspects of this interaction are synergistic while others are
      antagonistic. We propose that the positional information received by a cell at a
      particular location within the wing imaginal disc depends on the balance of Dpp
      to Gbb-60A signaling. Furthermore, the critical ratio of Gbb-60A to Dpp signaling
      appears to be mediated by both Tkv and Sax type I receptors.

PMID- 9636087
TI  - Identification of an evolutionarily conserved 110 base-pair cis-acting regulatory
      sequence that governs Wnt-1 expression in the murine neural plate.
AB  - The generation of anterior-posterior polarity in the vertebrate brain requires
      the establishment of regional domains of gene expression at early somite stages.
      Wnt-1 encodes a signal that is expressed in the developing midbrain and is
      essential for midbrain and anterior hindbrain development. Previous work
      identified a 5.5 kilobase region located downstream of the Wnt-1 coding sequence
      which is necessary and sufficient for Wnt-1 expression in vivo. Using a
      transgenic mouse reporter assay, we have now identified a 110 base pair
      regulatory sequence within the 5.5 kilobase enhancer, which is sufficient for
      expression of a lacZ reporter in the approximate Wnt-1 pattern at neural plate
      stages. Multimers of this element driving Wnt-1 expression can partially rescue
      the midbrain-hindbrain phenotype of Wnt-1(-/-) embryos. The possibility that this
      region represents an evolutionarily conserved regulatory module is suggested by
      the identification of a highly homologous region located downstream of the wnt-1
      gene in the pufferfish (Fugu rubripes). These sequences are capable of
      appropriate temporal and spatial activation of a reporter gene in the embryonic
      mouse midbrain; although, later aspects of the Wnt-1 expression pattern are
      absent. Genetic evidence has implicated Pax transcription factors in the
      regulation of Wnt-1. Although Pax-2 binds to the 110 base pair murine regulatory
      element in vitro, the location of the binding sites could not be precisely
      established and mutation of two putative low affinity sites did not abolish
      activation of a Wnt-1 reporter transgene in vivo. Thus, it is unlikely that Pax
      proteins regulate Wnt-1 by direct interactions with this cis-acting regulatory
      region. Our analysis of the 110 base pair minimal regulatory element suggests
      that Wnt-1 regulation is complex, involving different regulatory interactions for
      activation and the later maintenance of transgene expression in the dorsal
      midbrain and ventral diencephalon, and at the midbrain-hindbrain junction.

PMID- 9636088
TI  - faint sausage encodes a novel extracellular protein of the immunoglobulin
      superfamily required for cell migration and the establishment of normal axonal
      pathways in the Drosophila nervous system.
AB  - We examined the structure of the nervous system in Drosophila embryos homozygous
      for a null mutation in the faint sausage (fas) gene. In the peripheral nervous
      system (PNS) of fas mutants, neurons fail to delaminate from the ectodermal
      epithelium; in the central nervous system (CNS), the positions of neuronal cell
      bodies and glial cells are abnormal and normal axonal pathways do not form.
      Sequence analysis of fas cDNAs revealed that the fas protein product has
      characteristics of an extracellular protein and that it is a novel member of the
      immunoglobulin (Ig) superfamily. In situ hybridization demonstrated that fas
      transcripts are expressed throughout the embryo but they are in relatively high
      concentrations in the lateral ectoderm, from which the peripheral nervous system
      delaminates and in the CNS. Antiserum directed against Fas protein was found to
      stain neurons but not glia in the CNS. We conclude that fas encodes a protein
      that, in the developing nervous system, is present on the surface of neurons and
      is essential for nerve cell migration and the establishment of axonal pathways.

PMID- 9636089
TI  - Phasic boosting of medial perforant path-evoked granule cell output time-locked
      to spontaneous dentate EEG spikes in awake rats.
AB  - Dentate spikes (DSs) are positive-going field potential transients that occur
      intermittently in the hilar region of the dentate gyrus during alert wakefulness
      and slow-wave sleep. The function of dentate spikes is unknown; they have been
      suggested to be triggered by perforant path input and are associated with firing
      of hilar interneurons and inhibition of CA3 pyramidal cells. Here we investigated
      the effect of DSs on medial perforant path (MPP)-granule cell-evoked transmission
      in freely moving rats. The MPP was stimulated selectively in the angular bundle
      while evoked field potentials and the EEG were recorded with a vertical
      multielectrode array in the dentate gyrus. DSs were identified readily on the
      basis of their characteristic voltage-versus-depth profile, amplitude, duration,
      and state dependency. Using on-line detection of the DS peak, the timing of MPP
      stimulation relative to single DSs was controlled. DS-triggered evoked responses
      were compared with conventional, manually evoked responses in still-alert
      wakefulness (awake immobility) and, in some cases, slow-wave sleep. Input-output
      curves were obtained with stimulation on the positive DS peak (0 delay) and at
      delays of 50, 100, and 500 ms. Stimulation on the peak DS was associated with a
      significant increase in the population spike amplitude, a reduction in population
      spike latency, and a decrease in the field excitatory postsynaptic potential
      (fEPSP) slope, relative to manual stimulation. Granule cell excitability was
      enhanced markedly during DSs, as indicated by a mean 93% increase in the
      population spike amplitude and a leftward shift in the fEPSP-spike relation.
      Maximum effects occurred at the DS peak, and lasted between 50 and 100 ms. Paired
      pulse inhibition of the population spike was unaffected, indicating intact
      recurrent inhibition during DSs. The results demonstrate enhancement of perforant
      path-evoked granule cell output time-locked to DSs. DSs therefore may function to
      intermittently boost excitatory transmission in the entorhinal cortex-dentate
      gyrus-CA3 circuit. Such a mechanism may be important in the natural induction of
      long-term potentiation in the dentate gyrus and CA3 regions.

PMID- 9636090
TI  - Pointing in 3D space to remembered targets. I. Kinesthetic versus visual target
      presentation.
AB  - This study investigated the influence of different modalities of target
      information (visual, kinesthetic) on the accuracy, kinematics, and interjoint
      coordination of pointing movements to remembered targets. The targets were
      presented by a robot arm in five locations in three-dimensional (3D) space,
      either as a point of light in a dark room ("visual" condition), or
      kinesthetically. Relative pointing accuracy in the visual compared with
      kinesthetic conditions was influenced by the target location: pointing errors
      were the largest for the visual targets most eccentric relative to the subject's
      head. In addition, for the two most lateral targets, the final arm positions
      were, on average, closer to the center than the targets in the visual condition
      and farther from the center than the targets in the kinesthetic conditions. This
      result suggests that the pattern of errors in the visual condition described
      elsewhere ("range effect") may derive from visual processing rather than motor
      planning and implementation. Two modes of kinesthetic target presentation were
      utilized. During "passive" kinesthetic presentation of the target, the
      experimenter moved the subject's relaxed arm. Alternately, in "active"
      kinesthetic presentation of the target, the subject actively (with minimal help
      from the experimenter) moved his arm. No visual feedback was allowed in either
      kinesthetic condition. The variability in the final fingertip position was
      significantly smaller in the active condition than in the passive condition. In
      contrast, variability in the final values of arm orientation angles did not
      differ significantly in the active and passive conditions. This apparent
      contradiction may be resolved by the fact that, for the given target location,
      the influence of the deviation of these angles in the given trial from their
      average values on the position of the fingertip tended to be mutually
      compensated, and this tendency was stronger in the active condition. Our analysis
      of the correlations among the arm orientation angles and of the relationship
      between the initial and final arm configurations suggests that the kinesthetic
      conditions enabled the implementation of a mixture of strategies for achieving
      accuracy. The first strategy is to use a specific memory of an adequate arm
      configuration (that assumed during target presentation), such that accuracy is
      achieved by using this memory as a template. The second strategy is to use
      synergistically coordinating joint angles, such that accuracy is achieved by
      focusing on a specific endpoint that can be reached by a range of equivalent arm
      positions. The latter strategy was better utilized in the active condition. In
      conclusion, our results indicate that human subjects can use diverse sensory
      information to achieve comparable final accuracy, but that the details of the
      strategies employed differ with the kind of information available.

PMID- 9636091
TI  - Ionic basis for serotonin-induced bistable membrane properties in guinea pig
      trigeminal motoneurons.
AB  - Intracellular recordings and pharmacological manipulations were employed to
      investigate the ionic basis for serotonin-induced bistable membrane behaviors in
      guinea pig trigeminal motoneurons (TMNs). In voltage clamp, 10 microM serotonin
      (5-HT) induced a region of negative slope resistance (NSR) in the steady-state
      current-voltage (I-V) relationship at potentials less negative than -58 mV,
      creating the necessary conditions for membrane bistability. The contributions of
      sustained Na+ and Ca2+ currents to the generation of the NSR were investigated
      using specific ion channel antagonists and agonists. The NSR was eliminated by
      the L-type Ca2+ channel antagonist nifedipine (5-10 microM), indicating the
      contribution of L channels. In nifedipine, inward rectification was present in
      the I-V relationship in a similar voltage range (greater than -58 mV). This
      region was subsequently linearized by tetrodotoxin (TTX), indicating the presence
      of a persistent Na+ current. When the 5-HT-induced NSR was eliminated by
      perfusion in low Ca2+ solution (0.4 mM), it was restored by the Na+ channel
      agonist veratridine (10 microM). Commensurate with bistability, in current clamp
      during bath application of 5-HT, plateau potentials were elicited by transient
      depolarizing or hyperpolarizing stimuli. Plateau potentials evoked by
      depolarization were observed under control and TTX conditions, but were blocked
      by nifedipine, suggesting the participation of an L-type Ca2+ current. Plateau
      potentials initiated after release from hyperpolarization (anode break) were
      blocked by 300 microM Ni2+, suggesting the responses relied on deinactivation of
      a T-type Ca2+ current. Conditional bursting was also observed in 5-HT. Nifedipine
      or low Ca2+ solutions blocked bursting, and the L-channel agonist Bay K 8644 (10
      microM) extended the duration of individual bursts, demonstrating the role of L
      type Ca2+ currents. Interestingly, when bursting was blocked by nifedipine or low
      Ca2+, it could be restored by veratridine application via enhancement of the
      persistent Na+ current. We conclude that bistable membrane behaviors in TMNs are
      mediated by L-type Ca2+ and persistent Na+ currents. 5-HT is associated with
      enhancement of TMN activity during oral-motor activity; the induction of bistable
      membrane properties by 5-HT represents a cellular mechanism for this enhancement.

PMID- 9636092
TI  - Spatiotemporal structure of cortical activity: properties and behavioral
      relevance.
AB  - The study was designed to reveal occurrences of precise firing sequences (PFSs)
      in cortical activity and to test their behavioral relevance. Two monkeys were
      trained to perform a delayed-response paradigm and to open puzzle boxes.
      Extracellular activity was recorded from neurons in premotor and prefrontal areas
      with an array of six microelectrodes. An algorithm was developed to detect PFSs,
      defined as a set of three spikes and two intervals with a precision of +/-1 ms
      repeating significantly more than expected by chance. The expected level of
      repetition was computed based on the firing rate and the pairwise correlation of
      the participating units, assuming a Poisson distribution of event counts.
      Accordingly, the search for PFSs was corrected for rate modulations. PFSs were
      found in 24/25 recording sessions. Most PFSs (76%) were composed of spikes of
      more than one unit but usually not more than two units (67%). The PFSs spanned
      hundreds of milliseconds, and the average interval between two events within the
      PFSs was 200 ms. No traces of periodic oscillations were found in the PFS
      intervals. The bins of the matrix that were defined as PFSs were isolated
      temporally: the spikes that generated PFSs were not associated with high
      frequency bursts or rapid coherent rate fluctuations. A given PFS tended to be
      correlated with the animal's behavior. Furthermore, for 19% of the PFS pairs that
      shared the same unit composition, each member of the pair was associated with a
      different type of behavior. The PFSs often appeared in clusters that were
      associated with particular phases of the behavior. The firing rate of single
      units did not provide a full explanation for the timing and structure of these
      clusters. A reduced spike train (RST) was defined for each unit by taking all
      spikes of that unit that were part of any PFS. In 88% of the cases the degree of
      modulation of the RST was higher than that of the complete spike train. The
      results suggest that relevant information is carried by the fine temporal
      structure of cortical activity. A coding scheme that involves such temporal
      structures is rich and sufficiently flexible to facilitate a rapid organization
      of cortical neurons into functional groups. The results can be accounted for by
      the synfire chain model, which suggests that cortical activity is mediated by
      synchronous activation of neural groups in a reverberatory mode.

PMID- 9636093
TI  - Three-dimensional analysis of spontaneous and thalamically evoked gamma
      oscillations in auditory cortex.
AB  - The purpose of this study was to investigate interactions among laminar cell
      populations producing spontaneous and evoked high-frequency (approximately 40 Hz)
      gamma oscillations in auditory cortex. Electrocortical oscillations were recorded
      using a 64-channel epipial electrode array and a 16-channel linear laminar
      electrode array while electrical stimulation was delivered to the posterior
      intralaminar (PIL) nucleus. Spontaneous gamma oscillations, and those evoked by
      PIL stimulation, are confined to a location overlapping primary and secondary
      auditory cortex. Current source-density and principal components analysis of
      laminar recordings at this site indicate that the auditory evoked potential (AEP)
      complex is characterized by a stereotyped asynchronous activation of supra- and
      infragranular cell populations. Similar analysis of spontaneous and evoked gamma
      waves reveals a close spatiotemporal similarity to the laminar AEP, indicating
      rhythmic interactions between supra- and infragranular cell groups during these
      oscillatory phenomena. We conclude that neural circuit interactions producing the
      laminar AEP onset in auditory cortex are the same as those generating evoked and
      spontaneous gamma oscillations.

PMID- 9636094
TI  - Contribution of Ca2+-activated K+ channels to central chemosensitivity in
      cultivated neurons of fetal rat medulla.
AB  - Neurons in fetal rat medullary slices that exhibited spontaneous electrical
      activity after blockade of synaptic transmission were investigated for their
      response to decreases in extracellular pH. Increases in [H+] (induced either by
      fixed acid or increases in PCO2) induced a significant increase in the frequency
      of action potentials, associated with a membrane depolarization, and/or increases
      in the slope of the interspike depolarization. In addition, CO2/H+ prolonged the
      repolarizing phase of action potentials and reduced the afterhyperpolarization,
      suggesting that K+ channels were the primary site of CO2/H+ action. The type of
      K+ channel that was modulated by CO2/H+ was identified by application of agents
      that inhibited Ca2+-activated K+ channels either directly (tetraethylammonium
      chloride, TEA) or indirectly (Cd2+ ions) by inhibiting Ca2+ influx. CO2/H+
      effects on neuronal activity were abolished after application of these blockers.
      The contribution of Ca2+-activated K+ channels to H+ sensitivity of these neurons
      was confirmed further in voltage-clamp experiments in which outward rectifying I
      V curves were recorded that revealed a zero current potential of -70 mV. CO2/H+
      induced a prominent reduction in outward currents and shifted the zero current
      potential to more positive membrane potentials (mean -63 mV). The CO2/H+
      sensitive current reversed at -72 mV and was blocked by external application of
      TEA. It is concluded that CO2/H+ exerts its stimulatory effects on fetal
      medullary neurons by inhibition of Ca2+-activated K+ channels, either directly or
      indirectly, by blocking voltage-dependent Ca2+ channels, which in turn results in
      a reduction of K+ efflux and in cell depolarization.

PMID- 9636095
TI  - Properties of horizontal saccades accompanied by blinks.
AB  - Using the magnetic search coil technique to record eye and lid movements, we
      investigated the effect of voluntary blinks on horizontal saccades in five normal
      human subjects. The main goal of the study was to determine whether changes in
      the dynamics of saccades with blinks could be accounted for by a superposition of
      the eye movements induced by blinks as subjects fixated a stationary target and
      saccadic movements made without a blink. First, subjects made voluntary blinks as
      they fixed on stationary targets located straight ahead or 20 degrees to the
      right or left. They then made saccades between two continuously visible targets
      20 or 40 degrees apart, while either attempting not to blink, or voluntarily
      blinking, with each saccade. During fixation of a target located straight ahead,
      blinks induced brief downward and nasalward deflections of eye position. When
      subjects looked at targets located at right or left 20 degrees, similar initial
      movements were made by four of the subjects, but the amplitude of the adducted
      eye was reduced by 65% and was followed by a larger temporalward movement. Blinks
      caused substantial changes in the dynamic properties of saccades. For 20 degrees
      saccades made with blinks, peak velocity and peak acceleration were decreased by
      approximately 20% in all subjects compared with saccades made without blinks.
      Blinks caused the duration of 20 degrees saccades to increase, on average, by
      36%. On the other hand, blinks had only small effects on the gain of saccades.
      Blinks had little influence on the relative velocities of centrifugal versus
      centripetal saccades, and abducting versus adducting saccades. Three of five
      subjects showed a significantly increased incidence of dynamic overshoot in
      saccades accompanied by blinks, especially for 20 degrees movements. Taken with
      other evidence, this finding suggests that saccadic omnipause neurons are
      inhibited by blinks, which have longer duration than the saccades that company
      them. In conclusion, the changes in dynamic properties of saccades brought about
      by blinks cannot be accounted for simply by a summation of gaze perturbations
      produced by blinks during fixation and saccadic eye movements made without
      blinks. Our findings, especially the appearance of dynamic overshoots, suggest
      that blinks affect the central programming of saccades. These effects of blinks
      need to be taken into account during studies of the dynamic properties of
      saccades.

PMID- 9636096
TI  - Differential regulation of synaptic inputs to dentate hilar border interneurons
      by metabotropic glutamate receptors.
AB  - Regulation of synaptic transmission by metabotropic glutamate receptors (mGluRs)
      was examined at two excitatory inputs to interneurons with cell bodies at the
      granule cell-hilus border in hippocampal slices taken from neonatal rats.
      Subgroup-selective mGluR agonists altered the reliability, or probability of
      transmitter release, of evoked minimal excitatory synaptic inputs and decreased
      the amplitudes of excitatory postsynaptic currents (EPSCs) evoked with
      conventional stimulation. The group II-selective agonist, (2S,1R',2R',3R')-2-(2,
      3-dicarboxylcyclopropyl) glycine (DCG-IV; 1 microM), reversibly depressed the
      reliability of EPSCs evoked by stimulation of the dentate granule cell layer.
      However, DCG-IV had no significant effect on EPSCs evoked by CA3 stimulation in
      the majority (82%) of hilar border interneurons. Both the group III-selective
      agonist, -(+)-2-amino-4-phosphonobutyric acid (-AP4; 3 microM), and the group I
      selective agonist, (RS)-3,5-dihydroxyphenylglycine (DHPG; 20 microM) reversibly
      depressed synaptic input to interneurons from both CA3 and the granule cell
      layer. We conclude that multiple pharmacologically distinct mGluRs
      presynaptically regulate synaptic transmission at two excitatory inputs to hilar
      border interneurons. Further, the degree of mGluR-meditated depression of
      excitatory drive is greater at synapses from dentate granule cells onto
      interneurons than at synapses from CA3 pyramidal cells.

PMID- 9636097
TI  - Effect of bicuculline on thalamic activity: a direct blockade of IAHP in
      reticularis neurons.
AB  - The thalamic reticular nucleus (RTN) is the major source of inhibitory contacts
      in the thalamus and thus plays an important role in regulating the excitability
      of the thalamocortical network. Inhibition occurs through GABAergic synapses on
      relay cells as well as through GABAergic synapses between reticularis neurons
      themselves. Here we report that the role and mechanisms of this inhibition, which
      frequently have been studied using N-methyl derivatives of the gamma-aminobutyric
      acid-A (GABAA) receptor antagonist bicuculline, should be revisited. Using the
      whole cell patch-clamp technique in thalamic slices from young rats, we observed
      an enhancement by bicuculline methiodide, methobromide, and methochloride
      (collectively referred to as bicuculline-M; 5-60 microM) of the low-threshold
      calcium spike burst in RTN neurons that persisted in the presence of tetrodotoxin
      (1 microM) and was not reproduced in picrotoxin (100-300 microM). The effect did
      not involve activation of any GABA receptor subtype. Voltage-clamp recordings
      showed that bicuculline-M blocked the current underlying the low-threshold spike
      burst afterhyperpolarization (AHP), an effect that was mimicked by apamin (100
      nM). Recordings from nucleated patches extracted from reticularis neurons
      demonstrated that this effect was not mediated by modulation of the release of an
      unidentified neurotransmitter but that bicuculline-M directly blocks small
      conductance (SK) channels. The AHP-blocking effect also was observed in other
      brain regions, demonstrating that although bicuculline-M is a potent GABAA
      receptor antagonist, it is of limited value in assessing GABAergic network
      interactions, which should be studied using picrotoxin or bicuculline-free base.
      However, bicuculline-M may provide a useful tool for developing nonpeptide
      antagonists of SK channels.

PMID- 9636098
TI  - Matching patterns of activity in primate prefrontal area 8a and parietal area 7ip
      neurons during a spatial working memory task.
AB  - Single-unit recording studies of posterior parietal neurons have indicated a
      similarity of neuronal activation to that observed in the dorsolateral prefrontal
      cortex in relation to performance of delayed saccade tasks. A key issue addressed
      in the present study is whether the different classes of neuronal activity
      observed in these tasks are encountered more frequently in one or the other area
      or otherwise exhibit region-specific properties. The present study is the first
      to directly compare these patterns of neuronal activity by alternately recording
      from parietal area 7ip and prefrontal area 8a, under the identical behavioral
      conditions, within the same hemisphere of two monkeys performing an oculomotor
      delayed response task. The firing rate of 222 posterior parietal and 235
      prefrontal neurons significantly changed during the cue, delay, and/or saccade
      periods of the task. Neuronal responses in the two areas could be distinguished
      only by subtle differences in their incidence and timing. Thus neurons responding
      to the cue appeared earliest and were more frequent among the task-related
      neurons within parietal cortex, whereas neurons exhibiting delay-period activity
      accounted for a larger proportion of task-related neurons in prefrontal cortex.
      Otherwise, the task-related neuronal activities were remarkably similar. Cue
      period activity in prefrontal and parietal cortex exhibited comparable spatial
      tuning and temporal duration characteristics, taking the form of phasic, tonic,
      or combined phasic/tonic excitation in both cortical populations. Neurons in both
      cortical areas exhibited sustained activity during the delay period with nearly
      identical spatial tuning. The various patterns of delay-period activity-tonic,
      increasing or decreasing, alone or in combination with greater activation during
      cue and/or saccade periods-likewise were distributed to both cortical areas.
      Finally, similarities in the two populations extended to the proportion and
      spatial tuning of presaccadic and postsaccadic neuronal activity occurring in
      relation to the memory-guided saccade. The present findings support and extend
      evidence for a faithful duplication of receptive field properties and virtually
      every other dimension of task-related activity observed when parietal and
      prefrontal cortex are recruited to a common task. This striking similarity
      attests to the principal that information shared by a prefrontal region and a
      sensory association area with which it is connected is domain specific and not
      subject to hierarchical elaboration, as is evident at earlier stages of
      visuospatial processing.

PMID- 9636099
TI  - Effects of intrathecal alpha1- and alpha2-noradrenergic agonists and
      norepinephrine on locomotion in chronic spinal cats.
AB  - Noradrenergic drugs, acting on alpha adrenoceptors, have been found to play an
      important role in the initiation and modulation of locomotor pattern in adult
      cats after spinal cord transection. There are at least two subtypes of alpha
      adrenoceptors, alpha1 and alpha2 adrenoceptors. The aim of this study was to
      investigate the effects of selective alpha1 and alpha2 agonists in the initiation
      and modulation of locomotion in adult chronic cats in the early and late stages
      after complete transection at T13. Five cats, chronically implanted with an
      intrathecal cannula and electromyographic (EMG) electrodes were used in this
      study. Noradrenergic drugs including alpha2 agonists (clonidine, tizanidine, and
      oxymetazoline) and an antagonist, yohimbine, one alpha1 agonist (methoxamine),
      and a blocker, prazosin, as well as norepinephrine were injected intrathecally.
      EMG activity synchronized to video images of the hindlimbs were recorded before
      and after each drug injection. The results show differential effects of alpha1
      and alpha2 agonists in the initiation of locomotion in early spinal cats (i.e.,
      in the first week or so when there is no spontaneous locomotion) and in the
      modulation of locomotion and cutaneous reflexes in the late-spinal cats (i.e.,
      when cats have recovered spontaneous locomotion). In early spinal cats, all three
      alpha2 agonists were found to initiate locomotion, although their action had a
      different time course. The alpha1 agonist methoxamine induced bouts of nice
      locomotor activity in three spinal cats some hours after injection but only
      induced sustained locomotion in one cat in which the effects were blocked by the
      alpha1 antagonist prazosin. In late spinal cats, although alpha2 agonists
      markedly increased the cycle duration and flexor muscle burst duration and
      decreased the weight support or extensor activity (effects blocked by an alpha2
      antagonist, yohimbine), alpha1 agonist increased the weight support and primarily
      the extensor activity of the hindlimbs without markedly changing the timing of
      the step cycle. Although alpha2 agonists, especially clonidine, markedly reduced
      the cutaneous excitability and augmented the foot drag, the alpha1 agonist was
      found to increase the cutaneous reflex excitability. This is in line with
      previously reported differential effects of activation of the two receptors on
      motoneuron excitability and reflex transmission. Noradrenaline, the
      neurotransmitter itself, increased the cycle duration and at the same time
      retained the cutaneous excitability, thus exerting both alpha1 and alpha2
      effects. This work therefore suggests that different subclasses of noradrenergic
      drugs could be used to more specifically target aspects of locomotor deficits in
      patients after spinal injury or diseases.

PMID- 9636100
TI  - Cooperative mechanisms between leg joints of Carausius morosus I. Nonspiking
      interneurons that contribute to interjoint coordination.
AB  - Three nonspiking interneurons are described in this paper that influence the
      activity of the motor neurons of three muscles of the proximal leg joints of the
      stick insect. Interneurons were recorded and stained intracellularly by glass
      microelectrodes; motor neurons were recorded extracellularly with oil-hook
      electrodes. The motor neurons innervate the two subcoxal muscles, the protractor
      and retractor coxae, and the thoracic part of the depressor trochanteris muscle.
      The latter spans the subcoxal joint before inserting the trochanter, thus
      coupling the two proximal joints mechanically. The three interneurons are briefly
      described here. First, interneuron NS 1 was known to become more excited during
      the swing phase of the rear and the stance phase of the middle leg. When
      depolarized it excited several motor neurons of the retractor coxae. This
      investigation revealed that it inhibits the activity of protractor and thoracic
      depressor motor neurons when depolarized as well. In a pilocarpine-activated
      animal, the membrane potential showed oscillations in phase with the activity of
      protractor motor neurons, suggesting that NS 1 might contribute to the transition
      from swing to stance movement. Second, interneuron NS 2 inhibits motor neurons of
      protractor and thoracic depressor when depolarized. In both a quiescent and a
      pilocarpine-activated animal, hyperpolarizing stimuli excite motor neurons of
      both muscles via disinhibition. In one active animal the disinhibiting stimuli
      were sufficient to generate swing-like movements of the leg. In pilocarpine
      activated preparations the membrane potential oscillated in correlation with the
      motor neuronal activity of the protractor coxae and thoracic depressor muscle.
      Hyperpolarizing stimuli induced or reinforced the protractor and thoracic
      depressor bursts and inhibited the activity of the motor neurons of the retractor
      coxae muscle, the antagonistic muscle of the protractor. Therefore interneuron NS
      2 can be regarded as an important premotor interneuron for the switching from
      stance to swing and from swing to stance. Finally, interneuron NS 3 inhibits the
      spontaneously active motor neurons of both motor neuron pools in the quiescent
      animal. During pilocarpine-induced protractor bursts, depolarizing stimuli
      applied to the interneuron excited several protractor motor neurons with large
      action potentials and one motor neuron of the thoracic depressor. No oscillations
      of the membrane potentials were observed. Therefore this interneuron might
      contribute to the generation of rapid leg movements. The results demonstrated
      that the two proximal joints are coupled not only mechanically but also neurally
      and that the thoracic part of the depressor appears to function as a part of the
      swing-generating system.

PMID- 9636101
TI  - Cooperative mechanisms between leg joints of Carausius morosus II. Motor neuron
      activity and influence of conditional bursting interneuron.
AB  - The activity of the motor neuron pools of the protractor coxae muscle and of the
      thoracic part of the depressor trochanteris muscle during forward walking in the
      stick insect was investigated, and a spiking local interneuron, able to produce
      "endogenous bursting" and innervating both motor neuron pools, was identified.
      Extracellular recordings of the motor neurons innervating the protractor and the
      thoracic depressor of front, middle, and rear legs, respectively, were made with
      oil-hook electrodes from the peripheral nerves nl2c and nl4a while the animals
      were walking on a styrofoam treadwheel. The corresponding leg movements were
      registered and phase histograms were created with the software Spike2.
      Intracellular recordings were made in the neuropile of the metathoracic ganglion
      with glass electrodes filled with the dye Lucifer yellow. In all three legs
      measured (front, middle, and rear), both motor neuron pools increased their
      activity during the swing movement. The increase in the activity of the
      protractor motor neurons started at the end of the stance approximately 100 ms
      before reaching the posterior extreme position (PEP), and the activity of the
      large-sized depressor motor neurons increased as soon as the tarsus was lifted at
      the PEP. A local spiking interneuron was identified that excited both motor
      neuron pools. In 4 of 23 recordings the interneuron started to burst in synchrony
      with protractor and thoracic depressor motor neurons. During bursting a
      depolarizing stimulus reinforced and a hyperpolarizing stimulus inhibited the
      activity of both motor neuron pools. Thus we conclude that the thoracic part of
      the depressor trochanteris muscle might be a component of the neuromuscular
      system that shapes the swing movement. The two proximal joints, subcoxal and coxa
      trochanter, connected mechanically via the thoracic part of the depressor
      trochanteris muscle, are also connected neurally by segmental and intersegmental
      spiking interneurons (this paper) and by nonspiking local interneurons (see
      companion paper).

PMID- 9636102
TI  - AMPA and NMDA receptors expressed by differentiating Xenopus spinal neurons.
AB  - N-methyl--aspartate (NMDA) receptors are often the first ionotropic glutamate
      receptors expressed at early stages of development and appear to influence
      neuronal differentiation by mediating Ca2+ influx. Although less well studied,
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors also
      can generate Ca2+ elevations and may have developmental roles. We document the
      presence of AMPA and NMDA class receptors and the absence of kainate class
      receptors with whole cell voltage-clamp recordings from Xenopus embryonic spinal
      neurons differentiated in vitro. Reversal potential measurements indicate that
      AMPA receptors are permeable to Ca2+ both in differentiated neurons and at the
      time they first are expressed. The PCa/Pmonocation of 1.9 is close to that of
      cloned Ca2+-permeable AMPA receptors expressed in heterologous systems. Ca2+
      imaging reveals that Ca2+ elevations are elicited by AMPA or NMDA in the absence
      of Mg2+. The amplitudes and durations of these agonist-induced Ca2+ elevations
      are similar to those of spontaneous Ca2+ transients known to act as
      differentiation signals in these cells. Two sources of Ca2+ amplify AMPA- and
      NMDA-induced Ca2+ elevations. Activation of voltage-gated Ca2+ channels by AMPA-
      or NMDA-mediated depolarization contributes approximately 15 or 30% of cytosolic
      Ca2+ elevations, respectively. Activation of either class of receptor produces
      elevations of Ca2+ that elicit further release of Ca2+ from thapsigargin
      sensitive but ryanodine-insensitive stores, contributing an additional
      approximately 30% of Ca2+ elevations. Voltage-clamp recordings and Ca2+ imaging
      both show that these spinal neurons express functional AMPA receptors soon after
      neurite initiation and before expression of NMDA receptors. The Ca2+ permeability
      of AMPA receptors, their ability to generate significant elevations of [Ca2+]i,
      and their appearance before synapse formation position them to play roles in
      neural development. Spontaneous release of agonists from growth cones is detected
      with glutamate receptors in outside-out patches, suggesting that spinal neurons
      are early, nonsynaptic sources of glutamate that can influence neuronal
      differentiation in vivo.

PMID- 9636103
TI  - Changes in quantal size distributions upon experimental variations in the
      probability of release at striatal inhibitory synapses.
AB  - Postsynaptic inhibitory gamma-aminobutyric acid-A (GABAA)-receptor-mediated
      current responses were measured using simultaneous pre- and postsynaptic whole
      cell recordings in primary cell cultures of rat striatum. Substitution of Sr2+
      for extracellular Ca2+ strongly desynchronized the inhibitory postsynaptic
      currents (IPSCs), resulting in a succession of asynchronous IPSCs (asIPSCs). The
      rise times and decay time constants of individual evoked asIPSCs were not
      significantly different from those of miniature IPSCs that are the result of
      spontaneous vesicular release of GABA. Thus asIPSCs reflect quantal transmission
      at the individual contacts made by one presynaptic neuron on the recorded
      postsynaptic cell. Increasing the concentration of Sr2+ from 2 to 10 mM and
      decreasing that of Mg2+ from 5 to 1 mM produced an increase in the frequency of
      asIPSCs consistent with an enhancement of the mean probability of release (Pr).
      At the same time the amplitude distribution of asIPSCs was shifted toward larger
      values, whereas responses to exogenously applied GABA on average were slightly
      decreased in amplitude. Application of the GABAB-receptor agonist baclofen (3-10
      microM) strongly reduced the frequency of asIPSC, consistent with a decrease in
      Pr, and led to a shift of the amplitude distribution toward smaller values.
      Baclofen had no effect on responses to exogenously applied GABA. In summary, our
      data suggest that at striatal inhibitory connections the weight of single
      contacts may be controlled presynaptically by variation in the amount of
      transmitter released.

PMID- 9636104
TI  - Calcium-sensitive calcium influx in photoreceptor inner segments.
AB  - The effect of external calcium concentration ([Ca2+]o) on membrane potential
      dependent calcium signals in isolated tiger salamander rod and cone photoreceptor
      inner segments was investigated with patch-clamp and calcium imaging techniques.
      Mild depolarizations led to increases in intracellular Ca2+ levels ([Ca2+]i) that
      were smaller when [Ca2+]o was elevated to 10 mM than when it was 3 mM, even
      though maximum Ca2+ conductance increased 30% with the increase in [Ca2+]o. When
      external calcium was lowered to 1 mM [Ca2+]o, maximum Ca2+ conductance was
      reduced, as expected, but the mild depolarization-induced increase in [Ca2+]i was
      larger than in 3 mM [Ca2+]o. In contrast, when photoreceptors were strongly
      depolarized, the increase in [Ca2+]i was less when [Ca2+]o was reduced. An
      explanation for these observations comes from an assessment of Ca2+ channel
      gating in voltage-clamped photoreceptors under changing conditions of [Ca2+]o.
      Although Ca2+ conductance increased with increasing [Ca2+]o, surface charge
      effects dictated large shifts in the voltage dependence of Ca2+ channel gating.
      Relative to the control condition (3 mM [Ca2+]o), 10 mM [Ca2+]o shifted Ca2+
      channel activation 8 mV positive, reducing channel open probability over a broad
      range of potentials. Reducing [Ca2+]o to 1 mM reduced Ca2+ conductance but
      shifted Ca2+ channel activation negative by 6 mV. Thus the intracellular calcium
      signals reflect a balance between competing changes in gating and permeation of
      Ca2+ channels mediated by [Ca2+]o. In mildly depolarized cells, the [Ca2+]o
      induced changes in Ca2+ channel activation proved stronger than the [Ca2+]o
      induced changes in conductance. In response to the larger depolarizations caused
      by 80 mM [K+]o, the opposite is true, with conductance changes dominating the
      effects on channel activation.

PMID- 9636105
TI  - Ictal epileptiform activity in the CA3 region of hippocampal slices produced by
      pilocarpine.
AB  - Pilocarpine, a muscarinic agonist, produces status epilepticus that is associated
      with the later development of chronic recurrent seizures. When applied to rat
      hippocampal slices, pilocarpine (10 microM) produced brief (<200 ms) epileptiform
      discharges that resembled interictal activity that occurs between seizures, as
      well as more prolonged synchronous neuronal activation that lasted seconds (3-20
      s), and was comparable to ictal or seizures-like discharges. We assessed the
      factors that favored ictal patterns of activity and determined the biophysical
      properties of the ictal discharge. The probability of observing ictal discharges
      was increased when extracellular potassium ([K+]o) was increased from 5 to 7.5
      mM. Raising [K+]o to 10 mM resulted in loss of ictal patterns and, in 20 of 34
      slices, desynchronization of epileptiform activity. Making the artificial
      cerebrospinal fluid (ACSF) hyposmotic favored ictal discharges at 5 mM [K+]o, but
      shifted 7.5 mM [K+]o ACSF patterns to interictal discharges or desynchronized
      activity. Conversely, increasing osmolality suppressed ictal patterns. The
      pilocarpine-induced ictal discharges were blocked by atropine (1 microM, n = 5),
      a muscarinic antagonist, and pirenzepine (1 microM, n = 6), a selective M1
      receptor antagonist. Kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic
      acid receptor blockade stopped all epileptiform activity (n = 8). The N-methyl-
      aspartate antagonist ,-2-amino-5-phosphonovaleric acid (100 microM, n = 34) did
      not change the pattern of epileptiform activity but significantly increased the
      rate of interictal discharges and prolonged the duration of ictal discharges. The
      ictal discharge was characterized intracellularly by a depolarization that was
      associated with action potential generation and persisted as a membrane
      oscillation of 4-10 Hz. The ictal oscillations reversed in polarity at -22.7 +/-
      2.2 mV (n = 11) with current-clamp recordings and -20.9 +/- 3.1 mV (n = 7) with
      voltage-clamp recordings. The reversal potential of the ictal discharge in the
      presence of the gamma-aminobutyric acid-A blocker bicuculline (10 microM, n = 6)
      was -2.2 +/- 2.6 mV and was significantly different from that measured without
      bicuculline. Bicuculline added to 7.5 mM [K+]o and 10 microM pilocarpine did not
      cause epileptiform activity to change pattern but significantly increased the
      rate of interictal discharges and prolonged the ictal discharge duration. Both
      synaptic and nonsynaptic mechanisms are important for the generation of ictal
      patterns of epileptiform activity. Although the synchronous epileptiform activity
      produced by pilocarpine required fast glutamate-mediated synaptic transmission,
      the transition from an interictal to ictal pattern of activity depended on [K+]o
      and could be influenced by extracellular space.

PMID- 9636106
TI  - Neurophysiological correlates of unconditioned and conditioned feeding behavior
      in the pond snail Lymnaea stagnalis.
AB  - We used a behavioral appetitive learning paradigm followed by
      electrophysiological analysis to investigate the neuronal expression of
      appetitive conditioning in Lymnaea. We first established the levels of
      unconditioned and conditioned feeding responses in intact animals. We then
      demonstrated that neuronal correlates of both unconditioned responses to touch
      and food and a conditioned response to touch could be found in semi-intact
      preparations of the same animals that had been subjected to behavioral tests and
      conditioning trials. In the conditioning experiments, the experimental animals
      received 15 trials in which touch to the lips, the conditioned stimulus (CS), was
      paired with sucrose, the unconditioned food stimulus (US). Control animals
      received 15 presentations of either CS or US, or both, applied in a random
      manner. After training, a strong conditioned response to touch was established in
      the experimental but not in the control groups. For subsequent
      electrophysiological analysis of posttraining neuronal responses to the touch CS,
      semi-intact preparations were set up from the same animals that had been
      behaviorally conditioned or subjected to control procedures. Intracellular
      recordings, made from previously identified motoneurons of the feeding system,
      allowed the fictive feeding response to the CS to be monitored. In experimental
      preparations, touch applied to the lips evoked significantly more fictive feeding
      cycles than in controls, and this demonstrated the existence of a
      neurophysiological correlate of the appetitively conditioned response observed in
      the whole animals.

PMID- 9636107
TI  - Functional specialization in auditory cortex: responses to frequency-modulated
      stimuli in the cat's posterior auditory field.
AB  - The mammalian auditory cortex contains multiple fields but their functional role
      is poorly understood. Here we examine the responses of single neurons in the
      posterior auditory field (P) of barbiturate- and ketamine-anesthetized cats to
      frequency-modulated (FM) sweeps. FM sweeps traversed the excitatory response area
      of the neuron under study, and FM direction and the linear rate of change of
      frequency (RCF) were varied systematically. In some neurons, sweeps of different
      sound pressure levels (SPLs) also were tested. The response magnitude (number of
      spikes corrected for spontaneous activity) of nearly all field P neurons varied
      with RCF. RCF response functions displayed a variety of shapes, but most
      functions were of low-pass characteristic or peaked at rather low RCFs (<100
      kHz/s). Neurons with strong responses to high RCFs (high-pass or nonselective RCF
      response function characteristics) all displayed spike count-SPL functions to
      tone burst onsets that were monotonic or weakly nonmonotonic. RCF response
      functions and best RCFs often changed with SPL. For most neurons, FM directional
      sensitivity, quantified by a directional sensitivity (DS) index, also varied with
      RCF and SPL, but the mean and width of the distribution of DS indices across all
      neurons was independent of RCF. Analysis of response timing revealed that the
      phasic response of a neuron is triggered when the instantaneous frequency of the
      sweep reaches a particular value, the effective Fi. For a given neuron, values of
      effective Fi were independent of RCF, but depended on FM direction and SPL and
      were associated closely with the boundaries of the neuron's frequency versus
      amplitude response area. The standard deviation (SD) of the latency of the first
      spike of the response decreased with RCF. When SD was expressed relative to the
      rate of change of stimulus frequency, the resulting index of frequency jitter
      increased with RCF and did so rather uniformly in all neurons and largely
      independent of SPL. These properties suggest that many FM parameters are
      represented by, and may be encoded in, orderly temporal patterns across different
      neurons in addition to the strength of responses. When compared with neurons in
      primary and anterior auditory fields, field P neurons respond better to
      relatively slow FMs. Together with previous studies of responses to modulations
      of amplitude, such as tone onsets, our findings suggest more generally that field
      P may be best suited for processing signals that vary relatively slowly over
      time.

PMID- 9636108
TI  - Brain stem omnipause neurons and the control of combined eye-head gaze saccades
      in the alert cat.
AB  - When the head is unrestrained, rapid displacements of the visual axis-gaze shifts
      (eye-re-space)-are made by coordinated movements of the eyes (eye-re-head) and
      head (head-re-space). To address the problem of the neural control of gaze
      shifts, we studied and contrasted the discharges of omnipause neurons (OPNs)
      during a variety of combined eye-head gaze shifts and head-fixed eye saccades
      executed by alert cats. OPNs discharged tonically during intersaccadic intervals
      and at a reduced level during slow perisaccadic gaze movements sometimes
      accompanying saccades. Their activity ceased for the duration of the saccadic
      gaze shifts the animal executed, either by head-fixed eye saccades alone or by
      combined eye-head movements. This was true for all types of gaze shifts studied:
      active movements to visual targets; passive movements induced by whole-body
      rotation or by head rotation about stationary body; and electrically evoked
      movements by stimulation of the caudal part of the superior colliculus (SC), a
      central structure for gaze control. For combined eye-head gaze shifts, the OPN
      pause was therefore not correlated to the eye-in-head trajectory. For instance,
      in active gaze movements, the end of the pause was better correlated with the
      gaze end than with either the eye saccade end or the time of eye counterrotation.
      The hypothesis that cat OPNs participate in controlling gaze shifts is supported
      by these results, and also by the observation that the movements of both the eyes
      and the head were transiently interrupted by stimulation of OPNs during gaze
      shifts. However, we found that the OPN pause could be dissociated from the gaze
      motor-error signal producing the gaze shift. First, OPNs resumed discharging when
      perturbation of head motion briefly interrupted a gaze shift before its intended
      amplitude was attained. Second, stimulation of caudal SC sites in head-free cat
      elicited large head-free gaze shifts consistent with the creation of a large gaze
      motor-error signal. However, stimulation of the same sites in head-fixed cat
      produced small "goal-directed" eye saccades, and OPNs paused only for the
      duration of the latter; neither a pause nor an eye movement occurred when the
      same stimulation was applied with the eyes at the goal location. We conclude that
      OPNs can be controlled by neither a simple eye control system nor an absolute
      gaze control system. Our data cannot be accounted for by existing models
      describing the control of combined eye-head gaze shifts and therefore put new
      constraints on future models, which will have to incorporate all the various
      signals that act synergistically to control gaze shifts.

PMID- 9636109
TI  - Single olivocochlear neurons in the guinea pig. I. Binaural facilitation of
      responses to high-level noise.
AB  - Single medial olivocochlear (MOC) neurons were recorded from the cochlea of the
      anesthetized guinea pig. We used tones and noise presented monaurally and
      binaurally and measured responses for sounds up to 105 dB sound pressure level
      (SPL). For monaural sound, MOC neuron firing rates were usually higher for noise
      bursts than tone bursts, a situation not observed for afferent fibers of the
      auditory nerve that were sampled in the same preparations. MOC neurons also
      differed from afferent fibers in having less saturation of response. Some MOC
      neurons had responses that continued to increase even at high sound levels.
      Differences between MOC and afferent responses suggest that there is convergence
      in the pathway to olivocochlear neurons, possibly a combination of inputs that
      are at the characteristic frequency (CF) with others that are off the CF.
      Opposite-ear noise almost always facilitated the responses of MOC neurons to
      sounds in the main ear, the ear that best drives the unit. This binaural
      facilitation depends on several characteristics that pertain to the main ear: it
      is higher in neurons having a contralateral main ear (contra units), it is higher
      at main-ear sound levels that are moderate (approximately 65 dB SPL), and it is
      higher in neurons with low discharge rates to main-ear stimuli. Facilitation also
      depends on parameters of the opposite-ear sound: facilitation increases with
      noise level in the opposite ear until saturating, is greater for continuous noise
      than noise bursts, and is usually greater for noise than for tones. Using optimal
      opposite-ear facilitators and high-level stimuli, the firing rates of
      olivocochlear neurons range up to 140 spikes/s, whereas for moderate-level
      monaural stimuli the rates are <80 spikes/s. At high sound levels, firing rates
      of olivocochlear neurons increase with CF, an increase that may compensate for
      the known lower effectiveness of olivocochlear synapses on outer hair cells
      responding to high frequencies. Overall, our results demonstrate a high MOC
      response for binaural noise and suggest a prominent role for the MOC system in
      environments containing binaural noise of high level.

PMID- 9636110
TI  - Single olivocochlear neurons in the guinea pig. II. Response plasticity due to
      noise conditioning.
AB  - Previous studies have shown that daily, moderate-level sound exposure, or
      conditioning, can reduce injury from a subsequent high-level noise exposure. We
      tested the hypothesis that this conditioning produces an increased activity in
      the olivocochlear efferent reflex, a reflex known to provide protection to the
      cochlea. Guinea pigs were conditioned by a 10-day intermittent exposure to 2-4
      kHz noise at 85 dB sound pressure level. This conditioning is known to reduce
      damage from a subsequent high-level exposure to the same noise band. Responses to
      monaural and binaural sound were recorded from single medial olivocochlear (MOC)
      efferent neurons, and data from conditioned animals were compared with those
      obtained from unexposed controls. MOC neurons were classified by their response
      to noise bursts in the ipsilateral or contralateral ears as ipsi units, contra
      units, or either-ear units. There were no significant differences in the
      distributions of these unit types between control and conditioned animals. There
      were also no differences in other responses to monaural stimuli, including the
      distribution of characteristic frequencies (CFs), the sharpness of tuning, or
      thresholds at the CF. For binaural sound at high levels, particularly relevant to
      sound-evoked activation of the MOC reflex during acoustic overstimulation, the
      firing rates of MOC neurons with CFs just above the conditioning band showed
      slight (but statistically significant) elevations relative to control animals.
      Frequency regions just above the conditioning band also demonstrated maximum
      conditioning-related protection; thus protection could be due, in part, to long
      term changes in MOC discharge rates. For binaural sound at low levels, MOC firing
      rates in conditioned animals also were increased significantly relative to
      controls. Again, increases were largest for neurons with CFs just above the
      conditioning band. For equivalent monaural sound, rates were not significantly
      increased; thus, conditioning appears to increase binaural facilitation by
      opposite-ear sound. These data indicate that MOC neurons show long-term
      plasticity in acoustic responsiveness that is dependent on their acoustic
      history.

PMID- 9636111
TI  - Single-neuron modeling of LSO unit responses.
AB  - We investigated, using a computational model, the biophysical correlates of
      measured discharge patterns of lateral superior olive (LSO) neuron responses to
      monaural and binaural stimuli. The model's geometry was based on morphological
      data, and static electric properties of the model agree with available
      intracellular responses to hyperpolarizing current pulses. Inhibitory synapses
      were located on the soma and excitatory ones on the dendrites, which were modeled
      as passive cables. The active properties of the model were adjusted to agree with
      statistical measures derived from extracellular recordings. Calcium-dependent
      potassium channels supplemented the usual Hodgkin-Huxley characterization for the
      soma to produce observed serial interspike interval dependence characteristics.
      Intracellular calcium concentration is controlled by voltage- and calcium
      dependent potassium channels and by calcium diffusion and homeostatic mechanisms.
      By adjusting the density of the calcium-dependent potassium channels, we could
      span the observed range of transient response patterns found in different LSO
      neurons. Inputs from the two ears were modeled as Poisson processes to describe
      the responses to tone-burst stimuli. Transient and sustained responses to
      monaural and binaural tone-burst stimuli over a wide range of stimulus conditions
      could be well described by varying only the model's inputs. As found in
      recordings, model responses having similar discharge rates but different binaural
      stimulus combinations exhibited differences in interval statistics.

PMID- 9636112
TI  - Voltage-clamp analysis and computer simulation of a novel cesium-resistant A
      current in guinea pig laterodorsal tegmental neurons.
AB  - Increased firing of cholinergic neurons of the laterodorsal tegmental nucleus
      (LDT) plays a critical role in generating the behavioral states of arousal and
      rapid eye movement sleep. The majority of these neurons exhibit a prominent
      transient potassium current (IA) that shapes firing but the properties of which
      have not been examined in detail. Although IA has been reported to be blocked by
      intracellular cesium, the IA in LDT neurons appeared resistant to intracellular
      cesium. The present study compared the properties of this cesium-resistant
      current to those typically ascribed to IA. Whole cell recordings were obtained
      from LDT neurons (n = 67) in brain slices with potassium- or cesium-containing
      pipette solutions. A transient current was observed in cells dialyzed with each
      solution (KGluc-85%; CsGluc-79%). However, in cesium-dialyzed neurons, the
      transient current was inward at test potentials negative to about -35 mV.
      Extracellular 4-aminopyridine (4-AP; 2-5 mM) blocked both inward and outward
      current, suggesting the inward current was reversed IA rather than an unmasked
      transient calcium current as previously suggested. This conclusion was supported
      by increasing [K]o from 5 to 15 mM, which shifted the reversal potential
      positively for both inward and outward current (+17.89 +/- 0.41 mV; mean +/- SE).
      Moreover, recovery from inactivation was rapid (tau = 15.5 +/- 4 ms; n = 4), as
      reported for IA, and both inward and outward transient current persisted in
      calcium-free solution [0 calcium/4 mM ethylene glycol-bis(beta-aminoethyl ether)
      N,N,N', N'-tetraacetic acid; n = 4] and during cadmium-blockade of calcium
      currents (n = 3). Finally, the transient current was blocked by intracellular 4
      AP indicating that adequate dialysis occurred during the recordings. Thus the Cs
      resistant current is a subthreshold IA. We also estimated the voltage-dependence
      of activation (V1/2 = -45.8 +/- 2 mV, k = 5.21 +/- 0.62 mV, n = 6) and
      inactivation (V1/2 = -59. 0 +/- 2.38 mV, k = -5.4 +/- 0.49 mV, n = 3) of this
      current. Computer simulations using a morphologically accurate model cell
      indicated that except for the extreme case of only distal A-channels and a high
      intracellular resistivity, our parameter estimates were good approximations. In
      conclusion, guinea pig LDT neurons express subthreshold A-channels that are
      resistant to intracellular cesium ions. This suggests that these channels differ
      fundamentally in their ion permeation mechanism from those previously studied. It
      remains to be determined if Cs+ resistance is common among brain A-channels or if
      this property is conferred by known A-channel subunits.

PMID- 9636113
TI  - Anatomy and physiology of principal cells of the medial nucleus of the trapezoid
      body (MNTB) of the cat.
AB  - We have recorded from principal cells of the medial nucleus of the trapezoid body
      (MNTB) in the cat's superior olivary complex using either glass micropipettes
      filled with Neurobiotin or horseradish peroxidase for intracellular recording and
      subsequent labeling or extracellular metal microelectrodes relying on
      prepotentials and electrode location. Labeled principal cells had cell bodies
      that usually gave rise to one or two primary dendrites, which branched profusely
      in the vicinity of the cell. At the electron microscopic (EM) level, there was a
      dense synaptic terminal distribution on the cell body and proximal dendrites. Up
      to half the measured cell surface could be covered with excitatory terminals,
      whereas inhibitory terminals consistently covered about one-fifth. The distal
      dendrites were very sparsely innervated. The thick myelinated axon originated
      from the cell body and innervated nuclei exclusively in the ipsilateral auditory
      brain stem. These include the lateral superior olive (LSO), ventral nucleus of
      the lateral lemniscus, medial superior olive, dorsomedial and ventromedial
      periolivary nuclei, and the MNTB itself. At the EM level the myelinated
      collaterals gave rise to terminals that contained nonround vesicles and, in the
      LSO, were seen terminating on cell bodies and primary dendrites. Responses of
      MNTB cells were similar to their primary excitatory input, the globular bushy
      cell (GBC), in a number of ways. The spontaneous spike rate of MNTB cells with
      low characteristic frequencies (CFs) was low, whereas it tended to be higher for
      higher CF units. In response to short tones, a low frequency MNTB cell showed
      enhanced phase-locking abilities, relative to auditory nerve fibers. For cells
      with CFs >1 kHz, the short tone response often resembled the primary-like with
      notch response seen in many globular bushy cells, with a well-timed onset
      component. Exceptions to and variations of this standard response were also
      noted. When compared with GBCs with comparable CFs, the latency of the MNTB cell
      response was delayed slightly, as would be expected given the synapse interposed
      between the two cell types. Our data thus confirm that, in the cat, the MNTB
      receives and converts synaptic inputs from globular bushy cells into a reasonably
      accurate reproduction of the bushy cell spike response. This MNTB cell output
      then becomes an important inhibitory input to a number of ipsilateral auditory
      brain stem nuclei.

PMID- 9636114
TI  - A role for the dorsal column in nociceptive visceral input into the thalamus of
      primates.
AB  - A possible role of the dorsal column (DC) in the processing of visceral pain has
      gained attention after studies in the rat have revealed that the DC transmits a
      major part of the pelvic visceral nociceptive input from the colon into the
      thalamus. Furthermore, clinical interventions aimed at interrupting ascending DC
      axons near the midline were successful in relieving the pain suffered by patients
      with cancer of the pelvic organs. The purpose of this study was to check whether
      a DC lesion in monkeys would reduce the responses of thalamic neurons to graded
      colorectal distension (CRD) as in rats. Experiments were done on anesthetized
      male monkeys (Macaca fascicularis). Extracellular single cell recordings were
      made in the ventrolateral complex of the thalamus, mainly the ventral
      posterolateral (VPL) nucleus, in response to visceral and cutaneous stimulation.
      Of 80 VPL cells isolated, CRD activated 25, inhibited 25, and had no effect on 30
      neurons. The responses of six viscerosensitive VPL neurons were recorded before
      and after a lesion of the DC at or above the T10 spinal segment. Lesions of other
      spinal tracts were made after the DC lesion. The results show that the DC lesion
      significantly reduced the responses of the thalamic neurons tested with CRD by
      >50%. Lesions of other tracts did not have a consistent effect. These results
      corroborate findings in the rat and support the proposal that the DC plays an
      important role in transmitting nociceptive visceral input into the thalamus and
      subsequently in visceral pain.

PMID- 9636115
TI  - Synaptically evoked glutamate transport currents may be used to detect the
      expression of long-term potentiation in cerebellar culture.
AB  - Cerebellar long-term potentiation (LTP) is a use-dependent increase in the
      strength of the granule cell-Purkinje neuron synapse that occurs after brief
      stimulation of granule cell axons at 2-8 Hz. Previous work has shown that
      cerebellar LTP also may be seen when synaptic currents are evoked in granule cell
      glial cell pairs in culture. This finding suggests a model in which cerebellar
      LTP is expressed presynaptically and therefore may be detected by either neuronal
      or glial postsynaptic cells. However, synaptic currents evoked in both granule
      cell-glial cell pairs and granule cell-Purkinje neuron pairs in culture are
      mediated primarily by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      (AMPA)/kainate receptors, raising the possibility that cerebellar LTP might be
      expressed postsynaptically in both glial cells and Purkinje neurons in a similar
      manner. To address this question, glutamate transport currents were recorded in
      granule cell-glial cell pairs in culture by pharmacological isolation. These
      currents were increased by substitution of internal Cl with NO3 and were blocked
      by -pyrrolidine-2,4-dicarboxylate, both characteristics of the major cloned
      Bergmann glial cell glutamate transporter, EAAT1. After acquisition of baseline
      responses, LTP of isolated transport current was evoked by stimulation at 4 Hz
      (100 pulses) and could be blocked by removal of external Ca during this
      stimulation. The expression of LTP was associated with a decrease in the rate of
      synaptic failures and a decrease in the degree of paired-pulse facilitation.
      These findings, when taken together with the previous observation that both
      Purkinje neuron and glial AMPA/kainate responses can be used to detect cerebellar
      LTP, strongly suggest that the expression of cerebellar LTP is, at least in part,
      presynaptic. This strategy should also be useful in illuminating the locus of
      expression of other model systems of information storage such as hippocampal
      LTP/long-term depression.

PMID- 9636116
TI  - Different combinations of GABAA and GABAC receptors confer distinct temporal
      properties to retinal synaptic responses.
AB  - This study addresses how gamma-aminobutyric acid-A(GABAA) and GABAC receptors
      confer distinct temporal properties to neuronal synaptic responses. The retina is
      a model system for the study of postsynaptic contributions to synaptic responses
      because GABAergic amacrine cells synapse onto neurons, which have different
      combinations of GABAA and GABAC receptors. It is not known, however, how GABAA
      versus GABAC receptors influence the time course of retinal synaptic responses or
      what proportion of inhibitory input is mediated by each receptor type. We
      examined the time courses of synaptic responses mediated by GABA receptors in
      ganglion and bipolar cells by recording currents evoked by activating amacrine
      cells with a stimulating electrode in the salamander retinal slice. The
      pharmacologically isolated, GABAergic synaptic currents were long-lasting in
      bipolar cells and relatively brief in ganglion cells. The receptors that mediated
      these temporally distinct synaptic responses exhibited different pharmacological
      properties. In ganglion cells, GABAergic synaptic currents were abolished by the
      GABAA receptor antagonists bicuculline or SR95531. In bipolar cells, the GABAC
      receptor antagonist 3-aminopropyl[methyl]phosphonic acid (3-APMPA) largely
      blocked GABAergic synaptic responses; the remaining response was blocked by
      bicuculline or SR95531. The GABAA receptor component of the bipolar cell response
      was relatively brief compared with the GABAC receptor component. Puffing GABA
      onto ganglion cell dendrites or bipolar cell terminals yielded similar
      pharmacological and kinetic results, indicating that transmitter release
      differences did not determine the response time courses. Moreover, the GABAC
      receptors on bipolar cells may be different from those reported in rat or fish
      retina because imidazole-4-acetic acid (I4AA), which acts as an antagonist in
      these preparations, acts as an agonist in salamander. Our data show that the
      prolonged synaptic responses in bipolar cells were mediated predominantly by
      GABAC receptors, whereas transient synaptic responses in ganglion cells were
      mediated by GABAA receptors.

PMID- 9636117
TI  - Model of cortical-basal ganglionic processing: encoding the serial order of
      sensory events.
AB  - Several lines of evidence suggest that the prefrontal (PF) cortex and basal
      ganglia are important in cognitive aspects of serial order in behavior. We
      present a modular neural network model of these areas that encodes the serial
      order of events into spatial patterns of PF activity. The model is based on the
      topographically specific circuits linking the PF with the basal ganglia. Each
      module traces a pathway from the PF, through the basal ganglia and thalamus, and
      back to the PF. The complete model consists of an array of modules interacting
      through recurrent corticostriatal projections and collateral inhibition between
      striatal spiny units. The model's architecture positions spiny units for the
      classification of cortical contexts and events and provides bistable cortical
      thalamic loops for sustaining a representation of these contextual events in
      working memory activations. The model was tested with a simulated version of a
      delayed-sequencing task. In single-unit studies, the task begins with the
      presentation of a sequence of target lights. After a short delay, the monkey must
      touch the targets in the order in which they were presented. When instantiated
      with randomly distributed corticostriatal weights, the model produces different
      patterns of PF activation in response to different target sequences. These
      patterns represent an unambiguous and spatially distributed encoding of the
      sequence. Parameter studies of these random networks were used to compare the
      computational consequences of collateral and feed-forward inhibition within the
      striatum. In addition, we studied the receptive fields of 20,640 model units and
      uncovered an interesting set of cue-, rank- and sequence-related responses that
      qualitatively resemble responses reported in single unit studies of the PF. The
      majority of units respond to more than one sequence of stimuli. A method for
      analyzing serial receptive fields is presented and utilized for comparing the
      model units to single-unit data.

PMID- 9636118
TI  - Inhibitory glutamate receptor channels in cultured lobster stomatogastric
      neurons.
AB  - Inhibitory glutamate receptor channels (IGluRs) are ligand-gated ionotropic
      receptors related to ionotropic gamma-aminobutyric acid (GABA) and glycine
      receptors and expressed in neural and muscular tissues. In the crustacean
      stomatogastric ganglion (STG), IGluRs mediate recurrent synaptic inhibition
      central to the rhythmogenic capabilities of its embedded neural circuits. IGluRs
      expressed in cultured spiny lobster STG neurons exhibited an EC50 of 1.2 mM and a
      Hill coefficient of 1.4. They were neither cross-activated nor cross-desensitized
      by GABA, although a distinct GABA-gated chloride current was observed. Glycine
      did not evoke any current from STG neurons. The IGluR was weakly blocked by the
      chloride channel blocker furosemide and the excitatory glutamate receptor
      antagonist6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), but was not inhibited by
      bicuculline methiodide, strychnine, kynurenic acid, gamma--glutamylglycine, or
      aspartate. Outside-out patch-clamp recordings were analyzed using the mean
      variance histogram technique. Under excised-patch conditions, the receptor
      exhibited only a single open state with an estimated unitary conductance of 80 +/
      8. 6 (SD) pS. The distinct GABA receptor also displayed a single open state with
      a conductance of 72 +/- 10 pS.

PMID- 9636119
TI  - Commutative saccadic generator is sufficient to control a 3-D ocular plant with
      pulleys.
AB  - One-dimensional models of oculomotor control rely on the fact that, when
      rotations around only one axis are considered, angular velocity is the derivative
      of orientation. However, when rotations around arbitrary axes [3-dimensional (3
      D) rotations] are considered, this property does not hold, because 3-D rotations
      are noncommutative. The noncommutativity of rotations has prompted a long debate
      over whether or not the oculomotor system has to account for this property of
      rotations by employing noncommutative operators. Recently, Raphan presented a
      model of the ocular plant that incorporates the orbital pulleys discovered, and
      qualitatively modeled, by Miller and colleagues. Using one simulation, Raphan
      showed that the pulley model could produce realistic saccades even when the
      neural controller is commutative. However, no proof was offered that the good
      behavior of the Raphan-Miller pulley model holds for saccades different from
      those simulated. We demonstrate mathematically that the Raphan-Miller pulley
      model always produces movements that have an accurate dynamic behavior. This is
      possible because, if the pulleys are properly placed, the oculomotor plant
      (extraocular muscles, orbital pulleys, and eyeball) in a sense appears
      commutative to the neural controller. We demonstrate this finding by studying the
      effect that the pulleys have on the different components of the innervation
      signal provided by the brain to the extraocular muscles. Because the pulleys make
      the axes of action of the extraocular muscles dependent on eye orientation, the
      effect of the innervation signals varies correspondingly as a function of eye
      orientation. In particular, the Pulse of innervation, which in classical models
      of the saccadic system encoded eye velocity, here encodes a different signal,
      which is very close to the derivative of eye orientation. In contrast, the Step
      of innervation always encodes orientation, whether or not the plant contains
      pulleys. Thus the Step can be produced by simply integrating the Pulse.
      Particular care will be given to describing how the pulleys can have this
      differential effect on the Pulse and the Step. We will show that, if orbital
      pulleys are properly located, the neural control of saccades can be greatly
      simplified. Furthermore, the neural implementation of Listing's Law is
      simplified: eye orientation will lie in Listing's Plane as long as the Pulse is
      generated in that plane. These results also have implications for the surgical
      treatment of strabismus.

PMID- 9636120
TI  - Role of the basal forebrain cholinergic projection in somatosensory cortical
      plasticity.
AB  - Trimming all but two whiskers in adult rats produces a predictable change in
      cortical cell-evoked responses characterized by increased responsiveness to the
      two intact whiskers and decreased responsiveness to the trimmed whiskers. This
      type of synaptic plasticity in rat somatic sensory cortex, called "whisker
      pairing plasticity," first appears in cells above and below the layer IV barrels.
      These are also the cortical layers that receive the densest cholinergic inputs
      from the nucleus basalis. The present study assesses whether the cholinergic
      inputs to cortex have a role in regulating whisker pairing plasticity. To do
      this, cholinergic basal forebrain fibers were eliminated using an immunotoxin
      specific for these fibers. A monoclonal antibody to the low-affinity nerve growth
      factor receptor 192 IgG, conjugated to the cytotoxin saporin, was injected into
      cortex to eliminate cholinergic fibers in the barrel field. The immunotoxin
      reduces acetylcholine esterase (AChE)-positive fibers in S1 cortex by >90% by 3
      wk after injection. Sham-depleted animals in which either saporin alone or
      saporin unconjugated to 192 IgG is injected into the cortex produces no decrease
      in AChE-positive fibers in cortex. Sham-depleted animals show the expected
      plasticity in barrel column neurons. In contrast, no plasticity develops in the
      ACh-depleted, 7-day whisker-paired animals. These results support the conclusion
      that the basal forebrain cholinergic projection to cortex is an important
      facilitator of synaptic plasticity in mature cortex.

PMID- 9636121
TI  - Synaptic connectivity of distinct hilar interneuron subpopulations.
AB  - Dual intracellular recordings of hilar interneurons and CA3 pyramidal cells were
      performed in transverse slices of guinea pig hippocampus in the presence of the
      convulsant compound 4-aminopyridine (4-AP) and ionotropic glutamate receptor
      antagonists. Under these conditions, interneurons burst fire synchronously,
      producing synchronized inhibitory postsynaptic potentials (sIPSPs) in pyramidal
      cells. Three different hilar interneuron subpopulations that contributed to the
      sIPSP were identified based on their projection properties and morphology. These
      three types were pyramidal-like stellate interneurons, spheroid interneurons, and
      oviform interneurons. Physiologically, pyramidal-like stellate interneurons could
      be differentiated from the other interneuron subpopulations because they
      generated short synchronized bursts of action potentials coincident with the
      hyperpolarizing and depolarizing gamma-aminobutyric acid-A (GABAA)-mediated
      inhibitory postsynaptic potentials (IPSPs) recorded in pyramidal cells. The
      bursts in pyramidal-like stellate cells were abolished by theGABAA-receptor
      blocker, bicuculline. In contrast, spheroid interneurons of the dentate-hilus (D
      H) border and oviform hilar interneurons exhibited prolonged bicuculline
      resistant bursts that occurred coincident with the GABAB pyramidal cell sIPSPs.
      Pyramidal-like stellate interneurons likely did not contribute to the generation
      of synchronized GABAB responses in hippocampal pyramidal cells. Spheroid
      interneurons were unique among these subpopulations of interneurons in that the
      bicuculline-resistant bursts in spheroid interneurons were sustained by a
      synaptic depolarization that persisted in the presence of antagonists of
      ionotropic glutamate, GABAA and GABAB receptors [6-cyano-7-nitroquinoxaline-2,3
      dione, 20 microM; 3-3(2-carboxipiperazine-4-yl)propyl-1-phosphonate, 20 microM;
      bicuculline, 10-15 microM; CGP 55845A, 20 microM]. This novel depolarizing
      potential reversed between -30 and 0 mV. No noticeable synaptic depolarization
      sustaining burst firing could be isolated in oviform interneurons, suggesting
      that firing in this interneuron subpopulation was synchronized by nonsynaptic
      mechanisms. The results of the present study indicate that the hilar inhibitory
      circuit is composed of at least three different subpopulations of interneurons,
      distinguishable by their morphological characteristics and synaptic inputs and
      outputs. These findings give further support to the hypothesis that there are
      distinct populations of interneurons producing GABAA and GABAB responses with
      defined functional roles within the hippocampal inhibitory circuit. Notably, we
      found that spheroid interneurons were unique among the hilar interneurons
      studied, in that the synchronized bursts observed in these cells are sustained by
      a novel ionotropic glutamate and GABA receptor-independent synaptic
      depolarization.

PMID- 9636122
TI  - Encoding of shape and orientation of objects indented into the monkey fingerpad
      by populations of slowly and rapidly adapting mechanoreceptors.
AB  - The peripheral neural representation of object shape and orientation was studied
      by recording the responses of a spatially distributed population of rapidly and
      slowly adapting type I mechanoreceptors (RAs and SAs, respectively) to objects of
      different shapes and orientations indented at a fixed location on the fingerpad
      of the anesthetized monkey. The toroidal objects had a radius of 5 mm on the
      major axis, and 1, 3, or 5 mm on the minor axis. Each object was indented into
      the fingerpad for 4 s at orientations of 0, 45, 90, and 135 degrees using a
      contact force of 15 gwt. Estimations of the population responses (PRs) were
      constructed by combining the responses of 91 SA and 97 RA single afferents at
      discrete times during the indentation. The PR was composed of the neural
      discharge rates (z coordinate) plotted at x and y coordinates of the most
      sensitive spot of the receptive field. The shapes of the PRs were related to the
      shapes of the objects by fitting the PRs with Gaussian surfaces. The orientations
      of the PRs were determined from weighted principal component analyses. The SA PR
      encoded both the orientation and shape of the objects, whereas the RA PR did
      neither. The SA PR orientation was biased toward the long axis of the finger. The
      RA PR encoded orientation only for the object with the highest curvature but did
      so ambiguously. Only the SA PR was well fit by a Gaussian surface. The shape of
      the object was discriminated by the SA PR within the first 500 ms of contact, and
      the form of the SA PR remained constant during the subsequent 3.5 s. This was
      manifested by constant widths of the PR along the major and minor axes despite a
      peak response that decreased from its maximum at 200 ms to an asymptotic value
      starting at 1 s. Thus the shape and orientation of each object were coded by the
      shape and orientation of the SA PR.

PMID- 9636124
TI  - fMRI study of face perception and memory using random stimulus sequences.
AB  - A new functional magnetic resonance imaging (fMRI) method was used to investigate
      the functional neuroanatomy of face perception and memory. Whole-brain fMRI data
      were acquired while four types of stimuli were presented sequentially in an
      unpredictable pseudorandom order at a rate of 0.5 Hz. Stimulus types were a
      single repeated memorized target face, unrepeated novel faces, nonsense scrambled
      faces, and a blank screen. Random stimulus sequences were designed to generate a
      functional response to each stimulus type that was uncorrelated with responses to
      other stimuli. This allowed fMRI responses to each stimulus type to be examined
      separately using multiple regression. Signal increases were found for all stimuli
      in ventral posterior cortex. Responses to intact faces extended to more anterior
      locations of occipitotemporal cortex than did responses to scrambled faces,
      consistent with previous studies of face perception. Responses evoked by novel
      faces were in regions of ventral occipitotemporal cortex medial to regions in
      which significant responses were evoked by the target face. The repeated target
      face stimulus also evoked activity in widely distributed regions of frontal and
      parietal cortex. These results demonstrate that cortical hemodynamic responses to
      interleaved novel and repeated stimuli can be distinguished and measured using
      fMRI with appropriate stimulus sequences and data analysis methods. This method
      can now be used to examine the neural systems involved in cognitive tasks that
      were previously impossible to study using positron emission tomography or fMRI.

PMID- 9636123
TI  - Modulation of the Ca2+-activated K+ current sIAHP by a phosphatase-kinase balance
      under basal conditions in rat CA1 pyramidal neurons.
AB  - The slow Ca2+-activated K+ current, sIAHP, underlying spike frequency adaptation,
      was recorded with the whole cell patch-clamp technique in CA1 pyramidal neurons
      in rat hippocampal slices. Inhibitors of serine/threonine protein phosphatases
      (microcystin, calyculin A, cantharidic acid) caused a gradual decrease of sIAHP
      amplitude, suggesting the presence of a basal phosphorylation-dephosphorylation
      turnover regulating sIAHP. Because selective calcineurin (PP-2B) inhibitors did
      not affect the amplitude of sIAHP, protein phosphatase 1 (PP-1) or 2A (PP-2A) are
      most likely involved in the basal regulation of this current. The ATP analogue,
      ATP-gamma-S, caused a gradual decrease in the sIAHP amplitude, supporting a role
      of protein phosphorylation in the basal modulation of sIAHP. When the protein
      kinase A (PKA) inhibitor adenosine-3', 5'-monophosphorothioate, Rp-isomer (Rp
      cAMPS) was coapplied with the phosphatase inhibitor microcystin, it prevented the
      decrease in the sIAHP amplitude that was observed when microcystin alone was
      applied. Furthermore, inhibition of PKA by Rp-cAMPS led to an increase in the
      sIAHP amplitude. Finally, an adenylyl cyclase inhibitor (SQ22, 536) and adenosine
      3',5'-cyclic monophosphate-specific type IV phosphodiesterase inhibitors (Ro 20
      1724 and rolipram) led to an increase or a decrease in the sIAHP amplitude,
      respectively. These findings suggest that a balance between basally active PKA
      and a phosphatase (PP-1 or PP-2A) is responsible for the tonic modulation of
      sIAHP, resulting in a continuous modulation of excitability and firing properties
      of hippocampal pyramidal neurons.

PMID- 9636125
TI  - Role of platelet-activating factor in long-term potentiation of the rat medial
      vestibular nuclei.
AB  - In rat brain stem slices, we investigated the role of platelet activating factor
      (PAF) in long-term potentiation (LTP) induced in the ventral part of the medial
      vestibular nuclei (MVN) by high-frequency stimulation (HFS) of the primary
      vestibular afferent. The synaptosomal PAF receptor antagonist, BN-52021 was
      administered before and after HFS. BN-52021 did not modify the vestibular
      potentials under basal conditions, but it reduced the magnitude of potentiation
      induced by HFS, which completely developed after the drug wash-out. The same
      effect was obtained by using CV-62091, a more potent PAF antagonist at microsomal
      binding sites, but with concentrations higher than those of BN-52021. By contrast
      both BN-52021 and CV-6209 had no effect on the potentiation once induced. This
      demonstrates that PAF is involved in the induction but not in the maintenance of
      vestibular long-term effect through activation of synaptosomal PAF receptors. In
      addition, we analyzed the effect of the PAF analogue, 1-O-hexadecyl-2-O-
      (methylcarbamyl)-sn-glycero-3-phosphocoline (MC-PAF) and the inactive PAF
      metabolite, 1-O-hexadecyl-sn-glycero-3-phosphocoline (Lyso-PAF) on vestibular
      responses. Our results show that MC-PAF, but not Lyso-PAF induced potentiation.
      This potentiation was prevented by D,L-2-amino 5-phosphonopentanoic acid,
      suggesting an involvement of N-methyl-D-aspartate receptors. Furthermore, under
      BN-52021 and CV-6209, the MC-PAF potentiation was reduced or abolished. The dose
      effect curve of MC-PAF showed a shift to the right greater under BN-52021 than
      under CV-6209, confirming the main dependence of MC-PAF potentiation on the
      activation of synaptosomal PAF receptors. Our results suggest that PAF can be
      released in the MVN after the activation of postsynaptic mechanisms triggering
      LTP, and it may act as a retrograde messenger which activates the presynaptic
      mechanisms facilitating synaptic plasticity.

PMID- 9636126
TI  - Signal timing across the macaque visual system.
AB  - The onset latencies of single-unit responses evoked by flashing visual stimuli
      were measured in the parvocellular (P) and magnocellular (M) layers of the dorsal
      lateral geniculate nucleus (LGNd) and in cortical visual areas V1, V2, V3, V4,
      middle temporal area (MT), medial superior temporal area (MST), and in the
      frontal eye field (FEF) in individual anesthetized monkeys. Identical procedures
      were carried out to assess latencies in each area, often in the same monkey,
      thereby permitting direct comparisons of timing across areas. This study presents
      the visual flash-evoked latencies for cells in areas where such data are common
      (V1 and V2), and are therefore a good standard, and also in areas where such data
      are sparse (LGNd M and P layers, MT, V4) or entirely lacking (V3, MST, and FEF in
      anesthetized preparation). Visual-evoked onset latencies were, on average, 17 ms
      shorter in the LGNd M layers than in the LGNd P layers. Visual responses occurred
      in V1 before any other cortical area. The next wave of activation occurred
      concurrently in areas V3, MT, MST, and FEF. Visual response latencies in areas V2
      and V4 were progressively later and more broadly distributed. These differences
      in the time course of activation across the dorsal and ventral streams provide
      important temporal constraints on theories of visual processing.

PMID- 9636127
TI  - Trophic and contact conditions modulate synapse formation between identified
      neurons.
AB  - We tested the ability of an identified interneuron from the mollusk, Lymnaea
      stagnalis, to reestablish appropriate synapses in vitro. In the CNS, the giant
      dopaminergic neuron, designated as right pedal dorsal one (RPeD1), makes an
      excitatory, chemical synapse with a pair of essentially identical postsynaptic
      cells known as visceral dorsal two and three (VD2/3). When the somata of the pre-
      and postsynaptic neurons were juxtaposed and cultured in vitro in defined medium,
      i.e. , a soma-soma synapse, only an inappropriate electrical synapse was
      observed. The postsynaptic cell still responded to applied dopamine, the
      presynaptic transmitter, indicating that the lack of chemical synapse formation
      was not due to lack of dopamine receptors. When the somata were cultured apart in
      conditioned medium (medium previously incubated with Lymnaea CNS, thereby
      deriving trophic factors), the cells exhibited overlapping neurite outgrowth that
      resulted in an appropriate excitatory, chemical synapse from RPeD1 to VD2/3. On
      the other hand, when the cell pair was cultured in a soma-soma configuration, but
      in conditioned medium, a mixed chemical-electrical synapse was observed. Because
      conditioned medium could partially overcome the limitations of the soma-soma
      configuration and initiate chemical synapse formation, this data suggests that
      conditioned medium contains a factor(s) that supports synaptogenesis.

PMID- 9636128
TI  - Periodicity of thalamic spindle waves is abolished by ZD7288,a blocker of Ih.
AB  - The actions of the novel bradycardiac agent ZD7288 [4-(N-ethyl-N-phenylamino)-1,
      2-dimethyl-6-(methylamino)pyrimidinium chloride] were investigated on the
      hyperpolarization-activated cation current Ih and on network activity in
      spontaneously spindling ferret lateral geniculate (LGNd) slices in vitro using
      intracellular recording techniques. In voltage-clamp recordings, local
      application of ZD7288 (1 mM in micropipette) resulted in a complete block of Ih,
      whereas in current-clamp recordings, application of this agent resulted in an
      abolition of the depolarizing sag activated by hyperpolarization and decreased
      the frequency of intrinsic delta-oscillations for which Ih acts as a pacemaker
      current. In addition, block of Ih with ZD7288 resulted in an abolition of the
      afterdepolarization (ADP) that follows repetitive hyperpolarization and rebound
      burst firing as well as that occurring in between spindle waves. The block of the
      ADP was associated with a block of the spindle wave refractory period such that
      continuous 6- to 10-Hz oscillations were generated throughout the network. These
      findings give further support to the hypothesis that Ih is critically involved in
      the generation of slow rhythmicity in synchronized thalamic activity.

PMID- 9636129
TI  - Pointing errors reflect biases in the perception of the initial hand position.
AB  - By comparing the visuomotor performance of 10 adult, normal subjects in three
      tasks, we investigated whether errors in pointing movements reflect biased
      estimations of the hand starting position. In a manual pointing task with no
      visual feedback, subjects aimed at 48 targets spaced regularly around two
      starting positions. Nine subjects exhibited a similar pattern of systematic
      errors across targets, i.e., a parallel shift of the end points that accounted,
      on average, for 49% of the total variability. The direction of the shift depended
      on the starting location. Systematic errors decreased dramatically in the second
      condition where subjects were allowed to see their hand before movement onset.
      The third task was to use a joystick held by the left hand to estimate the
      location of their (unseen) right hand. The systematic perceptual errors in this
      condition were found to be highly correlated with the motor errors in the first
      condition. The results support the following conclusions. 1) Kinesthetic
      estimation of hand position may be consistently biased. Some of the mechanisms
      responsible for these biases are always active, irrespective of whether position
      is estimated overtly (e.g., with a matching paradigm), or covertly as part of the
      motor planning for aimed movements. 2) Pointing errors reflect to a significant
      extent the erroneous estimation of initial hand position. This suggests that
      aimed hand movements are planned vectorially, i.e., in terms of distance and
      direction, rather than in terms of absolute position in space.

PMID- 9636130
TI  - Synaptic transmission and hippocampal long-term potentiation in olfactory cyclic
      nucleotide-gated channel type 1 null mouse.
AB  - Field potential recording was used to investigate properties of synaptic
      transmission and long-term potentiation (LTP) at Schaffer collateral-CA1 synapses
      in both hippocampal slices of mutant mice in which the alpha-subunit of the
      olfactory cyclic nucleotide-gated channel (alpha3/OCNC)1 was rendered null and
      also in slices prepared from their wild-type (Wt) littermates. Several measures
      of basal synaptic transmission were unaltered in the OCNC1 knockout (KO),
      including maximum field excitatory postsynaptic potential (fEPSP) slope, maximum
      fEPSP and fiber volley amplitude, and the function relating fiber volley
      amplitude to fEPSP slope and paired-pulse facilitation. When a high-frequency
      stimulation protocol was used to induce LTP, similar responses were seen in both
      groups [KO: 1 min, 299 +/- 50% (mean +/- SE), 60 min, 123 +/- 10%; Wt: 1 min, 287
      +/- 63%; 60 min, 132 +/- 19%). However, on theta-burst stimulation, the initial
      amplitude of LTP was smaller (1 min after induction, 147 +/- 16% of baseline) and
      the response decayed faster in the OCNC1 KO (60 min, 127 +/- 18%) than in Wt (1
      min, 200 +/- 14%; 60 min, 169 +/- 19%). Analysis of waveforms evoked by LTP
      inducing tetanic stimuli revealed a similar difference between groups. The
      development of potentiation throughout the tetanic stimulus was similar in OCNC1
      KO and Wt mice when high-frequency stimulation was used, but OCNC1 KO mice showed
      a significant decrease when compared with Wt mice receiving theta-burst
      stimulation. These results suggest that activation of cyclic nucleotide-gated
      channels may contribute to the induction of LTP by weaker, more physiological
      stimuli, possibly via Ca2+ influx.

PMID- 9636131
TI  - Form follows function: structure of an elongation factor G-ribosome complex.

PMID- 9636132
TI  - Three independent lines of evidence suggest retinoids as causal to schizophrenia.
AB  - Retinoid dysregulation may be an important factor in the etiology of
      schizophrenia. This hypothesis is supported by three independent lines of
      evidence that triangulate on retinoid involvement in schizophrenia: (i)
      congenital anomalies similar to those caused by retinoid dysfunction are found in
      schizophrenics and their relatives; (ii) those loci that have been suggestively
      linked to schizophrenia are also the loci of the genes of the retinoid cascade
      (convergent loci); and (iii) the transcriptional activation of the dopamine D2
      receptor and numerous schizophrenia candidate genes is regulated by retinoic
      acid. These findings suggest a close causal relationship between retinoids and
      the underlying pathophysiological defects in schizophrenia. This leads to
      specific strategies for linkage analyses in schizophrenia. In view of the
      heterodimeric nature of the retinoid nuclear receptor transcription factors,
      e.g., retinoid X receptor beta at chromosome 6p21.3 and retinoic acid receptor
      beta at 3p24.3, two-locus linkage models incorporating genes of the retinoid
      cascade and their heterodimeric partners, e.g., peroxisome proliferator-activated
      receptor alpha at chromosome 22q12-q13 or nuclear-related receptor 1 at
      chromosome 2q22-q23, are proposed. New treatment modalities using retinoid
      analogs to alter the downstream expression of the dopamine receptors and other
      genes that are targets of retinoid regulation, and that are thought to be
      involved in schizophrenia, are suggested.

PMID- 9636133
TI  - A coupled proton-transfer and twisting-motion fluorescence probe for lipid
      bilayers.
AB  - A new and sensitive molecular probe, 2-(2'-hydroxyphenyl)imidazo[1, 2-a]pyridine
      (HPIP), for monitoring structural changes in lipid bilayers is presented.
      Migration of HPIP from water into vesicles involves rupture of hydrogen (H) bonds
      with water and formation of an internal H bond once the probe is inside the
      vesicle. These structural changes of the dye allow the occurrence of a
      photoinduced intramolecular proton-transfer reaction and a subsequent
      twisting/rotational process upon electronic excitation of the probe. The
      resulting large Stokes-shifted fluorescence band depends on the twisting motion
      of the zwitterionic phototautomer and is characterized in vesicles of dimyristoyl
      phosphatidylcholine and in dipalmitoyl-phosphatidylcholine at the temperature
      range of interest and in the presence of cholesterol. Because the fluorescence of
      aqueous HPIP does not interfere in the emission of the probe within the vesicles,
      HPIP proton-transfer/twisting motion fluorescence directly allows us to monitor
      and quantify structural changes within bilayers. The static and dynamic
      fluorescence parameters are sensitive enough to such changes to suggest this
      photostable dye as a potential molecular probe of the physical properties of
      lipid bilayers.

PMID- 9636134
TI  - Antibody catalysis of peptidyl-prolyl cis-trans isomerization in the folding of
      RNase T1.
AB  - An antibody generated to an alpha-keto amide containing hapten 1 catalyzes the
      cis-trans isomerization of peptidyl-prolyl amide bonds in peptides and in the
      protein RNase T1. The antibody-catalyzed peptide isomerization reaction showed
      saturation kinetics for the cis-substrate, Suc-Ala-Ala-Pro-Phe-pNA, with a
      kcat/Km value of 883 s-1.M-1; the reaction was inhibited by the hapten analog 13
      (Ki = 3. 0 +/- 0.4 microM). Refolding of denatured RNase T1 to its native
      conformation also was catalyzed by the antibody, with the antibody-catalyzed
      folding reaction inhibitable both by the hapten 1 and hapten analog 13. These
      results demonstrate that antibodies can catalyze conformational changes in
      protein structure, a transformation involved in many cellular processes.

PMID- 9636135
TI  - Calculated 11B-13C NMR chemical shift relationship in hypercoordinate methonium
      and boronium ions.
AB  - The boronium-carbonium continuum was extended to include hypercoordinated
      protonated methanes and their boron analogs. The 11B NMR chemical shifts of the
      hypercoordinated hydriodo boron compounds and the 13C NMR chemical shifts of the
      corresponding isoelectronic and isostructural carbocations were calculated by
      using the GIAO-MP2 method. The data show good linear correlation between 11B and
      13C NMR chemical shifts, which indicates that the same factors that determine the
      chemical shifts of the boron nuclei also govern the chemical shifts of carbon
      nuclei of these hypercoordinated hydriodo compounds.

PMID- 9636136
TI  - Oceanic protection of prebiotic organic compounds from UV radiation.
AB  - It is frequently stated that UV light would cause massive destruction of
      prebiotic organic compounds because of the absence of an ozone layer. The
      elevated UV flux of the early sun compounds this problem. This applies to organic
      compounds of both terrestrial and extraterrestrial origin. Attempts to deal with
      this problem generally involve atmospheric absorbers. We show here that prebiotic
      organic polymers as well as several inorganic compounds are sufficient to protect
      oceanic organic molecules from UV degradation. This aqueous protection is in
      addition to any atmospheric UV absorbers and should be a ubiquitous planetary
      phenomenon serving to increase the size of planetary habitable zones.

PMID- 9636137
TI  - Broken symmetry and strangeness of the semiconductor impurity band metal
      insulator transition.
AB  - The filamentary model of the metal-insulator transition in randomly doped
      semiconductor impurity bands is geometrically equivalent to similar models for
      continuous transitions in dilute antiferromagnets and even to the lambda
      transition in liquid He, but the critical behaviors are different. The origin of
      these differences lies in two factors: quantum statistics and the presence of
      long range Coulomb forces on both sides of the transition in the electrical case.
      In the latter case, in addition to the main transition, there are two satellite
      transitions associated with disappearance of the filamentary structure in both
      insulating and metallic phases. These two satellite transitions were first
      identified by Fritzsche in 1958, and their physical origin is explained here in
      geometrical and topological terms that facilitate calculation of critical
      exponents.

PMID- 9636138
TI  - A stochastic approximation algorithm with Markov chain Monte-carlo method for
      incomplete data estimation problems.
AB  - We propose a general procedure for solving incomplete data estimation problems.
      The procedure can be used to find the maximum likelihood estimate or to solve
      estimating equations in difficult cases such as estimation with the censored or
      truncated regression model, the nonlinear structural measurement error model, and
      the random effects model. The procedure is based on the general principle of
      stochastic approximation and the Markov chain Monte-Carlo method. Applying the
      theory on adaptive algorithms, we derive conditions under which the proposed
      procedure converges. Simulation studies also indicate that the proposed procedure
      consistently converges to the maximum likelihood estimate for the structural
      measurement error logistic regression model.

PMID- 9636139
TI  - Defining the domains of type I collagen involved in heparin- binding and
      endothelial tube formation.
AB  - Cell surface heparan sulfate proteoglycan (HSPG) interactions with type I
      collagen may be a ubiquitous cell adhesion mechanism. However, the HSPG binding
      sites on type I collagen are unknown. Previously we mapped heparin binding to the
      vicinity of the type I collagen N terminus by electron microscopy. The present
      study has identified type I collagen sequences used for heparin binding and
      endothelial cell-collagen interactions. Using affinity coelectrophoresis, we
      found heparin to bind as follows: to type I collagen with high affinity (Kd
      approximately 150 nM); triple-helical peptides (THPs) including the basic N
      terminal sequence alpha1(I)87-92, KGHRGF, with intermediate affinities (Kd
      approximately 2 microM); and THPs including other collagenous sequences, or
      single-stranded sequences, negligibly (Kd >> 10 microM). Thus, heparin-type I
      collagen binding likely relies on an N-terminal basic triple-helical domain
      represented once within each monomer, and at multiple sites within fibrils. We
      next defined the features of type I collagen necessary for angiogenesis in a
      system in which type I collagen and heparin rapidly induce endothelial tube
      formation in vitro. When peptides, denatured or monomeric type I collagen, or
      type V collagen was substituted for type I collagen, no tubes formed. However,
      when peptides and type I collagen were tested together, only the most heparin
      avid THPs inhibited tube formation, likely by influencing cell interactions with
      collagen-heparin complexes. Thus, induction of endothelial tube morphogenesis by
      type I collagen may depend upon its triple-helical and fibrillar conformations
      and on the N-terminal heparin-binding site identified here.

PMID- 9636140
TI  - Tyrosine phosphorylation of paxillin and focal adhesion kinase by activation of
      muscarinic m3 receptors is dependent on integrin engagement by the extracellular
      matrix.
AB  - The G protein-coupled m1 and m3 muscarinic acetylcholine receptors increase
      tyrosine phosphorylation of several proteins, including the focal adhesion
      associated proteins paxillin and focal adhesion kinase (FAK), but the mechanism
      is not understood. Activation of integrins during adhesion of cells to
      extracellular matrix, or stimulation of quiescent cell monolayers with G protein
      coupled receptor ligands including bradykinin, bombesin, endothelin, vasopressin,
      and lysophosphatidic acid, also induces tyrosine phosphorylation of paxillin and
      FAK and formation of focal adhesions. These effects are generally independent of
      protein kinase C but are inhibited by agents that prevent cytoskeletal assembly
      or block activation of the small molecular weight G protein Rho. This report
      demonstrates that tyrosine phosphorylation of paxillin and FAK elicited by
      stimulation of muscarinic m3 receptors with the acetylcholine analog carbachol is
      inhibited by soluble peptides containing the arginine-glycine-aspartate motif
      (the recognition site for integrins found in adhesion proteins such as
      fibronectin) but is unaffected by peptides containing the inactive sequence
      arginine-glycine-glutamate. Tyrosine phosphorylation elicited by carbachol, but
      not by cell adhesion to fibronectin, is reduced by the protein kinase C inhibitor
      GF 109203X. The response to carbachol is dependent on the presence of
      fibronectin. Moreover, immunofluorescence studies show that carbachol treatment
      induces formation of stress fibers and focal adhesions. These results suggest
      that muscarinic receptor stimulation activates integrins via a protein kinase C
      dependent mechanism. The activated integrins transmit a signal into the cell's
      interior leading to tyrosine phosphorylation of paxillin and FAK. This represents
      a novel mechanism for regulation of tyrosine phosphorylation by muscarinic
      receptors.

PMID- 9636141
TI  - A synthetic all D-amino acid peptide corresponding to the N-terminal sequence of
      HIV-1 gp41 recognizes the wild-type fusion peptide in the membrane and inhibits
      HIV-1 envelope glycoprotein-mediated cell fusion.
AB  - Recent studies demonstrated that a synthetic fusion peptide of HIV-1 self
      associates in phospholipid membranes and inhibits HIV-1 envelope glycoprotein
      mediated cell fusion, presumably by interacting with the N-terminal domain of
      gp41 and forming inactive heteroaggregates [Kliger, Y., Aharoni, A., Rapaport,
      D., Jones, P., Blumenthal, R. & Shai, Y. (1997) J. Biol. Chem. 272, 13496-13505].
      Here, we show that a synthetic all D-amino acid peptide corresponding to the N
      terminal sequence of HIV-1 gp41 (D-WT) of HIV-1 associates with its enantiomeric
      wild-type fusion (WT) peptide in the membrane and inhibits cell fusion mediated
      by the HIV-1 envelope glycoprotein. D-WT does not inhibit cell fusion mediated by
      the HIV-2 envelope glycoprotein. WT and D-WT are equally potent in inducing
      membrane fusion. D-WT peptide but not WT peptide is resistant to proteolytic
      digestion. Structural analysis showed that the CD spectra of D-WT in
      trifluoroethanol/water is a mirror image of that of WT, and attenuated total
      reflectance-fourier transform infrared spectroscopy revealed similar structures
      and orientation for the two enantiomers in the membrane. The results reveal that
      the chirality of the synthetic peptide corresponding to the HIV-1 gp41 N-terminal
      sequence does not play a role in liposome fusion and that the peptides' chirality
      is not necessarily required for peptide-peptide interaction within the membrane
      environment. Furthermore, studies along these lines may provide criteria to
      design protease-resistant therapeutic agents against HIV and other viruses.

PMID- 9636142
TI  - alpha1-Antitrypsin Portland, a bioengineered serpin highly selective for furin:
      application as an antipathogenic agent.
AB  - The important role of furin in the proteolytic activation of many pathogenic
      molecules has made this endoprotease a target for the development of potent and
      selective antiproteolytic agents. Here, we demonstrate the utility of the protein
      based inhibitor alpha1-antitrypsin Portland (alpha1-PDX) as an antipathogenic
      agent that can be used prophylactically to block furin-dependent cell killing by
      Pseudomonas exotoxin A. Biochemical analysis of the specificity of a bacterially
      expressed His- and FLAG-tagged alpha1-PDX (alpha1-PDX/hf) revealed the
      selectivity of the alpha1-PDX/hf reactive site loop for furin (Ki, 600 pM) but
      not for other proprotein convertase family members or other unrelated
      endoproteases. Kinetic studies show that alpha1-PDX/hf inhibits furin by a slow
      tight-binding mechanism characteristic of serpin molecules and functions as a
      suicide substrate inhibitor. Once bound to furin's active site, alpha1-PDX/hf
      partitions with equal probability to undergo proteolysis by furin at the C
      terminal side of the reactive center -Arg355-Ile-Pro-Arg358- downward arrow or to
      form a kinetically trapped SDS-stable complex with the enzyme. This partitioning
      between the complex-forming and proteolytic pathways contributes to the ability
      of alpha1-PDX/hf to differentially inhibit members of the proprotein convertase
      family. Finally, we propose a structural model of the alpha1-PDX-reactive site
      loop that explains the high degree of enzyme selectivity of this serpin and which
      can be used to generate small molecule furin inhibitors.

PMID- 9636143
TI  - Supramolecular organization of immature and mature murine leukemia virus revealed
      by electron cryo-microscopy: implications for retroviral assembly mechanisms.
AB  - We have used electron cryo-microscopy and image analysis to examine the native
      structure of immature, protease-deficient (PR-) and mature, wild-type (WT)
      Moloney murine leukemia virus (MuLV). Maturational cleavage of the Gag
      polyprotein by the viral protease is associated with striking morphological
      changes. The PR- MuLV particles exhibit a rounded central core, which has a
      characteristic track-like shell on its surface, whereas the WT MuLV cores display
      a polygonal surface with loss of the track-like feature. The pleomorphic shape
      and inability to refine unique orientation angles suggest that neither the PR-
      nor the WT MuLV adheres to strict icosahedral symmetry. Nevertheless, the PR-
      MuLV particles do exhibit paracrystalline order with a spacing between Gag
      molecules of approximately 45 A and a length of approximately 200 A. Because of
      the pleomorphic shape and paracrystalline packing of the Gag-RNA complexes, we
      raise the possibility that assembly of MuLV is driven by protein-RNA, as well as
      protein-protein, interactions. The maturation process involves a dramatic
      reorganization of the packing arrangements within the ribonucleoprotein core with
      disordering and loosening of the individual protein components.

PMID- 9636144
TI  - Ethyl-substituted erythromycin derivatives produced by directed metabolic
      engineering.
AB  - A previously unknown chemical structure, 6-desmethyl-6-ethylerythromycin A (6
      ethylErA), was produced through directed genetic manipulation of the erythromycin
      (Er)-producing organism Saccharopolyspora erythraea. In an attempt to replace the
      methyl side chain at the C-6 position of the Er polyketide backbone with an ethyl
      moiety, the methylmalonate-specific acyltransferase (AT) domain of the Er
      polyketide synthase was replaced with an ethylmalonate-specific AT domain from
      the polyketide synthase involved in the synthesis of the 16-member macrolide
      niddamycin. The genetically altered strain was found to produce ErA, however, and
      not the ethyl-substituted derivative. When the strain was provided with
      precursors of ethylmalonate, a small quantity of a macrolide with the mass of 6
      ethylErA was produced in addition to ErA. Because substrate for the heterologous
      AT seemed to be limiting, crotonyl-CoA reductase, a primary metabolic enzyme
      involved in butyryl-CoA production in streptomycetes, was expressed in the
      strain. The primary macrolide produced by the reengineered strain was 6-ethylErA.

PMID- 9636145
TI  - A model for the structure of the P domains in the subtilisin-like prohormone
      convertases.
AB  - The proprotein convertases are a family of at least seven calcium-dependent
      endoproteases that process a wide variety of precursor proteins in the secretory
      pathway. All members of this family possess an N-terminal proregion, a subtilisin
      like catalytic module, and an additional downstream well-conserved region of
      approximately 150 amino acid residues, the P domain, which is not found in any
      other subtilase. The pro and catalytic domains cannot be expressed in the absence
      of the P domains; their thermodynamic instability may be attributable to the
      presence of large numbers of negatively charged Glu and Asp side chains in the
      substrate binding region for recognition of multibasic residue cleavage sites.
      Based on secondary structure predictions, we here propose that the P domains
      consist of 8-stranded beta-barrels with well-organized inner hydrophobic cores,
      and therefore are independently folded components of the proprotein convertases.
      We hypothesize further that the P domains are integrated through strong
      hydrophobic interactions with the catalytic domains, conferring structural
      stability and regulating the properties and activity of the convertases. A
      molecular model of these interdomain interactions is proposed in this report.

PMID- 9636146
TI  - Interaction of SP100 with HP1 proteins: a link between the promyelocytic leukemia
      associated nuclear bodies and the chromatin compartment.
AB  - The PML/SP100 nuclear bodies (NBs) were first described as discrete subnuclear
      structures containing the SP100 protein. Subsequently, they were shown to contain
      the PML protein which is part of the oncogenic PML-RARalpha hybrid produced by
      the t(15;17) chromosomal translocation characteristic of acute promyelocytic
      leukemia. Yet, the physiological role of these nuclear bodies remains unknown.
      Here, we show that SP100 binds to members of the heterochromatin protein 1 (HP1)
      families of non-histone chromosomal proteins. Further, we demonstrate that a
      naturally occurring splice variant of SP100, here called SP100-HMG, is a member
      of the high mobility group-1 (HMG-1) protein family and may thus possess DNA
      binding potential. Both HP1 and SP100-HMG concentrate in the PML/SP100 NBs, and
      overexpression of SP100 leads to enhanced accumulation of endogenous HP1 in these
      structures. When bound to a promoter, SP100, SP100-HMG and HP1 behave as
      transcriptional repressors in transfected mammalian cells. These observations
      present molecular evidence for an association between the PML/SP100 NBs and the
      chromatin nuclear compartment. They support a model in which the NBs may play a
      role in certain aspects of chromatin dynamics.

PMID- 9636147
TI  - Chromatin components as part of a putative transcriptional repressing complex.
AB  - The Drosophila HMG1-like protein DSP1 was identified by its ability to inhibit
      the transcriptional activating function of Dorsal in a promoter-specific fashion
      in yeast. We show here that DSP1 as well as its mammalian homolog hHMG2 bind to
      the mammalian protein SP100B and that SP100B in turn binds to human homologs of
      HP1. The latter is a Drosophila protein that is involved in transcriptional
      silencing. Each of these proteins represses transcription when tethered to DNA in
      mammalian cells. These results suggest how heterochromatin proteins might be
      recruited to specific sites on DNA with resultant specific effects on gene
      expression.

PMID- 9636148
TI  - Effective inhibition of influenza virus production in cultured cells by external
      guide sequences and ribonuclease P.
AB  - The polymerase (PB2) and nucleocapsid (NP) genes encoded by the genome of
      influenza virus are essential for replication of the virus. When synthetic genes
      that express RNAs for external guide sequences targeted to the mRNAs of the PB2
      and NP genes are stably incorporated into mouse cells in tissue culture,
      infection of these cells with influenza virus is nonproductive. Endogenous RNase
      P cleaves the targeted influenza virus mRNAs when they are in a complex with the
      external guide sequences. Targeting two different mRNAs simultaneously inhibits
      viral particle production more efficiently than does targeting only one mRNA.

PMID- 9636149
TI  - Two binding modes reveal flexibility in kinase/response regulator interactions in
      the bacterial chemotaxis pathway.
AB  - The crystal structure at 2.0-A resolution of the complex of the Escherichia coli
      chemotaxis response regulator CheY and the phosphoacceptor-binding domain (P2) of
      the kinase CheA is presented. The binding interface involves the fourth and fifth
      helices and fifth beta-strand of CheY and both helices of P2. Surprisingly, the
      two heterodimers in the asymmetric unit have two different binding modes
      involving the same interface, suggesting some flexibility in the binding regions.
      Significant conformational changes have occurred in CheY compared with previously
      determined unbound structures. The active site of CheY is exposed by the binding
      of the kinase domain, possibly to enhance phosphotransfer from CheA to CheY. The
      conformational changes upon complex formation as well as the observation that
      there are two different binding modes suggest that the plasticity of CheY is an
      essential feature of response regulator function.

PMID- 9636150
TI  - The N-terminal domain of PsaF: precise recognition site for binding and fast
      electron transfer from cytochrome c6 and plastocyanin to photosystem I of
      Chlamydomonas reinhardtii.
AB  - The PsaF-deficient mutant 3bF of Chlamydomonas reinhardtii was used to modify
      PsaF by nuclear transformation and site-directed mutagenesis. Four lysine
      residues in the N-terminal domain of PsaF, which have been postulated to form the
      positively charged face of a putative amphipathic alpha-helical structure were
      altered to K12P, K16Q, K23Q, and K30Q. The interactions between plastocyanin (pc)
      or cytochrome c6 (cyt c6) and photosystem I (PSI) isolated from wild type and the
      different mutants were analyzed using crosslinking techniques and flash
      absorption spectroscopy. The K23Q change drastically affected crosslinking of pc
      to PSI and electron transfer from pc and cyt c6 to PSI. The corresponding second
      order rate constants for binding of pc and cyt c6 were reduced by a factor of 13
      and 7, respectively. Smaller effects were observed for mutations K16Q and K30Q,
      whereas in K12P the binding was not changed relative to wild type. None of the
      mutations affected the half-life of the microsecond electron transfer performed
      within the intermolecular complex between the donors and PSI. The fact that these
      single amino acid changes within the N-terminal domain of PsaF have different
      effects on the electron transfer rate constants and dissociation constants for
      both electron donors suggests the existence of a rather precise recognition site
      for pc and cyt c6 that leads to the stabilization of the final electron transfer
      complex through electrostatic interactions.

PMID- 9636151
TI  - Tn552 transposase catalyzes concerted strand transfer in vitro.
AB  - The Tn552 transposase, a member of the DDE superfamily of transposase and
      retroviral integrase proteins, has been expressed in soluble form. The purified
      protein performs concerted strand transfer in vitro, efficiently pairing two
      preprocessed transposon ends and inserting them into target DNA. For maximum
      efficiency, both participating DNA ends must contain the two adjacent transposase
      binding sites that are the normal constituents of the Tn552 termini. As is the
      case with transposition in vivo, the insertions recovered from the reaction in
      vitro are flanked by repeats of a short target sequence, most frequently 6 bp.
      The reaction has stringent requirements for a divalent metal ion. Concerted
      strand transfer is most efficient with Mg2+. Although it stimulates strand
      transfer overall, Mn2+ promotes uncoupled, single-ended events at the expense of
      concerted insertions. The simplicity and efficiency of the Tn552 transposition
      system make it an attractive subject for structural and biochemical studies and a
      potentially useful genetic tool.

PMID- 9636152
TI  - Malignant transformation of early lymphoid progenitors in mice expressing an
      activated Blk tyrosine kinase.
AB  - The intracellular signals governing cellular proliferation and developmental
      progression during lymphocyte development are incompletely understood. The
      tyrosine kinase Blk is expressed preferentially in the B lineage, but its
      function in B cell development has been largely unexplored. We have generated
      transgenic mice expressing constitutively active Blk [Blk(Y495F)] in the B and T
      lymphoid compartments. Expression of Blk(Y495F) in the B lineage at levels
      similar to that of endogenous Blk induced B lymphoid tumors of limited clonality,
      whose phenotypes are characteristic of B cell progenitors at the proB/preB-I to
      preB-II transition. Expression of constitutively active Blk in the T lineage
      resulted in the appearance of clonal, thymic lymphomas composed of intermediate
      single positive cells. Taken together, these results indicate that specific B and
      T cell progenitor subsets are preferentially susceptible to transformation by
      Blk(Y495F) and suggest a role for Blk in the control of proliferation during B
      cell development.

PMID- 9636153
TI  - The yeast halotolerance determinant Hal3p is an inhibitory subunit of the Ppz1p
      Ser/Thr protein phosphatase.
AB  - Components of cellular stress responses can be identified by correlating changes
      in stress tolerance with gain or loss of function of defined genes. Previous work
      has shown that yeast cells deficient in Ppz1 protein phosphatase or
      overexpressing Hal3p, a novel regulatory protein of unknown function, exhibit
      increased resistance to sodium and lithium, whereas cells lacking Hal3p display
      increased sensitivity. These effects are largely a result of changes in
      expression of ENA1, encoding the major cation extrusion pump of yeast cells.
      Disruption or overexpression of HAL3 (also known as SIS2) has no effect on salt
      tolerance in the absence of PPZ1, suggesting that Hal3p might function upstream
      of Ppz1p in a novel signal transduction pathway. Hal3p is recovered from crude
      yeast homogenates by using immobilized, bacterially expressed Ppz1p fused to
      glutathione S-transferase, and it also copurifies with affinity-purified
      glutathione S-transferase-Ppz1p from yeast extracts. In both cases, the
      interaction is stronger when only the carboxyl-terminal catalytic phosphatase
      domain of Ppz1p is expressed. In vitro experiments reveal that the protein
      phosphatase activity of Ppz1p is inhibited by Hal3p. Overexpression of Hal3p
      suppresses the reduced growth rate because of the overexpression of Ppz1p and
      aggravates the lytic phenotype of a slt2/mpk1 mitogen-activated protein kinase
      mutant (thus mimicking the deletion of PPZ1). Therefore, Hal3p might modulate
      diverse physiological functions of the Ppz1 phosphatase, such as salt stress
      tolerance and cell cycle progression, by acting as a inhibitory subunit.

PMID- 9636154
TI  - In disperse solution, "osmotic stress" is a restricted case of preferential
      interactions.
AB  - In the practice of "osmotic stress," the effect of excluded cosolvents on a
      biochemical equilibrium is interpreted as the number of water molecules
      participating in the reaction. This action is attributed to lowering of solvent
      water activity by the cosolvent. This concept of osmotic stress in disperse
      solution is erroneous: (i) A cosolvent cannot be both excluded and inert, i.e.,
      noninteracting, because exclusion requires a positive free energy change; (ii) a
      decrease in water activity alone by addition of solute cannot affect an
      equilibrium when the reacting surface is in contact with the solvent; and (iii)
      osmotic stress in disperse solution is a restricted case of preferential
      interactions; the reaction is driven by the free energy of cosolvent exclusion,
      and the derived number of water molecules is solely a measure of the mutual
      perturbations of the chemical potentials of the cosolvent and the protein.

PMID- 9636155
TI  - Inhibition of hypoxia-inducible factor 1 activity by nitric oxide donors in
      hypoxia.
AB  - Nitric oxide (NO) is known to have various biologic and pathophysiologic effects
      on organisms. The molecular mechanisms by which NO exerts harmful effects are
      unknown, although various O2 radicals and ions that result from reactivity of NO
      are presumed to be involved. Here we report that adaptive cellular response
      controlled by the transcription factor hypoxia-inducible factor 1 (HIF-1) in
      hypoxia is suppressed by NO. Induction of erythropoietin and glycolytic aldolase
      A mRNAs in hypoxically cultured Hep3B cells, a human hepatoma cell line, was
      completely and partially inhibited, respectively, by the addition of sodium
      nitroprusside (SNP), which spontaneously releases NO. A reporter plasmid carrying
      four hypoxia-response element sequences connected to the luciferase structural
      gene was constructed and transfected into Hep3B cells. Inducibly expressed
      luciferase activity in hypoxia was inhibited by the addition of SNP and two other
      structurally different NO donors, S-nitroso-L-glutathione and 3
      morpholinosydnonimine, giving IC50 values of 7.8, 211, and 490 microM,
      respectively. Inhibition by SNP was also observed in Neuro 2A and HeLa cells,
      indicating that the inhibition was not cell-type-specific. The vascular
      endothelial growth factor promoter activity that is controlled by HIF-1 was also
      inhibited by SNP (IC50 = 6.6 microM). Induction generated by the addition of
      cobalt ion (this treatment mimics hypoxia) was also inhibited by SNP (IC50 = 2.5
      microM). Increased luciferase activity expressed by cotransfection of effector
      plasmids for HIF-1alpha or HIF-1alpha-like factor in hypoxia was also inhibited
      by the NO donor. We also showed that the inhibition was performed by blocking an
      activation step of HIF-1alpha to a DNA-binding form.

PMID- 9636156
TI  - Characterization of genes modulated during pheomelanogenesis using differential
      display.
AB  - Molecular and biochemical mechanisms that modulate the production of eumelanin or
      pheomelanin pigments involve the opposing effects of two intercellular signaling
      molecules, alpha-melanocyte stimulating hormone (MSH) and agouti signal protein
      (ASP). ASP is an antagonist of MSH signaling through the melanocyte-specific MSH
      receptor, although its mechanism(s) of action is controversial. We previously
      have reported significant down-regulation of all known melanogenic genes during
      the eumelanin to pheomelanin switch in murine hair follicle melanocytes and in
      cultured melanocytes treated with recombinant ASP. To identify factors that might
      be involved in the switch to pheomelanogenesis, we screened ASP-treated
      melanocytes by using differential display and identified three up-regulated
      genes: a DNA replication control protein, a basic helix-loop-helix transcription
      factor, and a novel gene. We have simultaneously identified six down-regulated
      genes in ASP-treated melanocytes; two of those encode tyrosinase and TRP2,
      melanogenic genes known to be down-regulated during pheomelanogenesis, which
      provide good internal controls for this approach. These results suggest that
      there are complex mechanisms involved in the switch to pheomelanin production,
      and that these modulated genes might be involved in the pleiotropic changes seen
      in yellow mice, including the change in coat color.

PMID- 9636157
TI  - Promotion of agonist activity of antiandrogens by the androgen receptor
      coactivator, ARA70, in human prostate cancer DU145 cells.
AB  - Although hormone therapy with antiandrogens has been widely used for the
      treatment of prostate cancer, some antiandrogens may act as androgen receptor
      (AR) agonists that may result in antiandrogen withdrawal syndrome. The molecular
      mechanism of this agonist response, however, remains unclear. Using mammalian two
      hybrid assay, we report that antiandrogens, hydroxyflutamide, bicalutamide
      (casodex), cyproterone acetate, and RU58841, and other compounds such as
      genistein and RU486, can promote the interaction between AR and its coactivator,
      ARA70, in a dose-dependent manner. The chloramphenicol acetyltransferase assay
      further demonstrates that these antiandrogens and related compounds significantly
      enhance the AR transcriptional activity by cotransfection of AR and ARA70 in a
      1:3 ratio into human prostate cancer DU145 cells. Our results suggest that the
      agonist activity of antiandrogens might occur with the proper interaction of AR
      and ARA70 in DU145 cells. These findings may provide a good model to develop
      better antiandrogens without agonist activity.

PMID- 9636158
TI  - 13C NMR study of the effects of leptin treatment on kinetics of hepatic
      intermediary metabolism.
AB  - The recent discovery of leptin receptors in peripheral tissue raises questions
      about which of leptin's biological actions arise from direct effects of the
      hormone on extraneural tissues and what intracellular mechanisms are responsible
      for leptin's effects on carbohydrate and lipid metabolism. The present study is
      focused on the action of leptin on hepatic metabolism. Nondestructive 13C NMR
      methodology was used to follow the kinetics of intermediary metabolism by
      monitoring flux of 13C-labeled substrate through several multistep pathways. In
      perfused liver from either ob/ob or lean mice, we found that acute treatment with
      leptin in vitro modulates pathways controlling carbohydrate flux into 13C-labeled
      glycogen, thereby rapidly enhancing synthesis by an insulin-independent
      mechanism. Acute treatment of ob/ob liver also caused a rapid stimulation of long
      chain fatty acid synthesis from 13C-labeled acetyl-CoA by the de novo synthesis
      route. Chronic leptin treatment in vivo induced homeostatic changes that resulted
      in a tripling of the rate of glycogen synthesis via the gluconeogenic pathway
      from [2-13C]pyruvate in ob/ob mouse liver perfused in the absence of the hormone.
      Consistent with the 13C NMR results, leptin treatment of the ob/ob mouse in vivo
      resulted in significantly increased hepatic glycogen synthase activity. Chronic
      treatment with leptin in vivo exerted the opposite effect of acute treatment in
      vitro and markedly decreased hepatic de novo synthesis of fatty acids in ob/ob
      mouse liver. In agreement with the 13C NMR findings, activities of hepatic acetyl
      CoA carboxylase and fatty acid synthase were significantly reduced by chronic
      treatment of the ob/ob mouse with leptin. Our data represent a demonstration of
      direct effects of leptin in the regulation of metabolism in the intact
      functioning liver.

PMID- 9636159
TI  - Mass spectrometry of ribosomes and ribosomal subunits.
AB  - Nanoflow electrospray ionization has been used to introduce intact Escherichia
      coli ribosomes into the ion source of a mass spectrometer. Mass spectra of
      remarkable quality result from a partial, but selective, dissociation of the
      particles within the mass spectrometer. Peaks in the spectra have been assigned
      to individual ribosomal proteins and to noncovalent complexes of up to five
      component proteins. The pattern of dissociation correlates strongly with
      predicted features of ribosomal protein-protein and protein-RNA interactions. The
      spectra allow the dynamics and state of folding of specific proteins to be
      investigated in the context of the intact ribosome. This study demonstrates a
      potentially general strategy to probe interactions within complex biological
      assemblies.

PMID- 9636160
TI  - Trans/cis (Z/E) photoisomerization of the chromophore of photoactive yellow
      protein is not a prerequisite for the initiation of the photocycle of this
      photoreceptor protein.
AB  - The chromophore of photoactive yellow protein (PYP) (i.e., 4-hydroxycinnamic
      acid) has been replaced by an analogue with a triple bond, rather than a double
      bond (by using 4-hydroxyphenylpropiolic acid in the reconstitution, yielding
      hybrid I) and by a "locked" chromophore (through reconstitution with 7
      hydroxycoumarin-3-carboxylic acid, in which a covalent bridge is present across
      the vinyl bond, resulting in hybrid II). These hybrids absorb maximally at 464
      and 443 nm, respectively, which indicates that in both hybrids the deprotonated
      chromophore does fit into the chromophore-binding pocket. Because the triple bond
      cannot undergo cis/trans (or E/Z) photoisomerization and because of the presence
      of the lock across the vinyl double bond in hybrid II, it was predicted that
      these two hybrids would not be able to photocycle. Surprisingly, both are able.
      We have demonstrated this ability by making use of transient absorption, low
      temperature absorption, and Fourier-transform infrared (FTIR) spectroscopy. Both
      hybrids, upon photoexcitation, display authentic photocycle signals in terms of a
      red-shifted intermediate; hybrid I, in addition, goes through a blue-shifted-like
      intermediate state, with very slow kinetics. We interpret these results as
      further evidence that rotation of the carbonyl group of the thioester-linked
      chromophore of PYP, proposed in a previous FTIR study and visualized in recent
      time-resolved x-ray diffraction experiments, is of critical importance for
      photoactivation of PYP.

PMID- 9636161
TI  - Antigen binding forces of individually addressed single-chain Fv antibody
      molecules.
AB  - Antibody single-chain Fv fragment (scFv) molecules that are specific for
      fluorescein have been engineered with a C-terminal cysteine for a directed
      immobilization on a flat gold surface. Individual scFv molecules can be
      identified by atomic force microscopy. For selected molecules the antigen binding
      forces are then determined by using a tip modified with covalently immobilized
      antigen. An scFv mutant of 12% lower free energy for ligand binding exhibits a
      statistically significant 20% lower binding force. This strategy of covalent
      immobilization and measuring well separated single molecules allows the
      characterization of ligand binding forces in molecular repertoires at the single
      molecule level and will provide a deeper insight into biorecognition processes.

PMID- 9636162
TI  - Adjustment of conformational flexibility is a key event in the thermal adaptation
      of proteins.
AB  - 3-Isopropylmalate dehydrogenase (IPMDH, E.C. 1.1.1.85) from the thermophilic
      bacterium Thermus thermophilus HB8 is homologous to IPMDH from the mesophilic
      Escherichia coli, but has an approximately 17 degreesC higher melting
      temperature. Its temperature optimum is 22-25 degreesC higher than that of the E.
      coli enzyme; however, it is hardly active at room temperature. The increased
      conformational rigidity required to stabilize the thermophilic enzyme against
      heat denaturation might explain its different temperature-activity profile.
      Hydrogen/deuterium exchange studies were performed on this thermophilic
      mesophilic enzyme pair to compare their conformational flexibilities. It was
      found that Th. thermophilus IPMDH is significantly more rigid at room temperature
      than E. coli IPMDH, whereas the enzymes have nearly identical flexibilities under
      their respective optimal working conditions, suggesting that evolutionary
      adaptation tends to maintain a "corresponding state" regarding conformational
      flexibility. These observations confirm that conformational fluctuations
      necessary for catalytic function are restricted at room temperature in the
      thermophilic enzyme, suggesting a close relationship between conformational
      flexibility and enzyme function.

PMID- 9636163
TI  - Structural basis of an embryonically lethal single Ala --> Thr mutation in the
      vnd/NK-2 homeodomain.
AB  - The structural and DNA binding behavior is described for an analog of the vnd/NK
      2 homeodomain, which contains a single amino acid residue alanine to threonine
      replacement in position 35 of the homeodomain. Multidimensional nuclear magnetic
      resonance, circular dichroism, and electrophoretic gel retardation assays were
      carried out on recombinant 80-aa residue proteins that encompass the wild-type
      and mutant homeodomains. The mutant A35T vnd/NK-2 homeodomain is unable to adopt
      a folded conformation free in solution at temperatures down to -5 degreesC in
      contrast to the behavior of the corresponding wild-type vnd/NK-2 homeodomain,
      which is folded into a functional three-dimensional structure below 25 degreesC.
      The A35T vnd/NK-2 binds specifically to the vnd/NK-2 target DNA sequence, but
      with an affinity that is 50-fold lower than that of the wild-type homeodomain.
      Although the three-dimensional structure of the mutant A35T vnd/NK-2 in the DNA
      bound state shows characteristic helix-turn-helix behavior similar to that of the
      wild-type homeodomain, a notable structural deviation in the mutant A35T analog
      is observed for the amide proton of leucine-40. The wild-type homeodomain forms
      an unusual i,i-5 hydrogen bond with the backbone amide oxygen of residue 35. In
      the A35T mutant this amide proton resonance is shifted upfield by 1.27 ppm
      relative to the resonance frequency for the wild-type analog, thereby indicating
      a significant alteration of this i,i-5 hydrogen bond.

PMID- 9636164
TI  - Arachidonic acid mediates angiotensin II effects on p21ras in renal proximal
      tubular cells via the tyrosine kinase-Shc-Grb2-Sos pathway.
AB  - In kidney epithelial cells, an angiotensin II (Ang II) type 2 receptor subtype
      (AT2) is linked to a membrane-associated phospholipase A2 (PLA2) and the mitogen
      activated protein kinase (MAPK) superfamily. However, the intervening steps in
      this linkage have not been determined. The aim of this study was to determine
      whether arachidonic acid mediates Ang II's effect on p21ras and if so, to
      ascertain the signaling mechanism(s). We observed that Ang II activated p21ras
      and that mepacrine, a phospholipase A2 inhibitor, blocked this effect. This
      activation was also inhibited by PD123319, an AT2 receptor antagonist but not by
      losartan, an AT1 receptor antagonist. Furthermore, Ang II caused rapid tyrosine
      phosphorylation of Shc and its association with Grb2. Arachidonic acid and
      linoleic acid mimicked Ang II-induced tyrosine phosphorylation of Shc and
      activation of p21ras. Moreover, Ang II and arachidonic acid induced an
      association between p21ras and Shc. We demonstrate that arachidonic acid mediates
      linkage of a G protein-coupled receptor to p21ras via Shc tyrosine
      phosphorylation and association with Grb2/Sos. These observations have important
      implications for other G protein-coupled receptors linked to a variety of
      phospholipases.

PMID- 9636165
TI  - Role of p38 mitogen-activated protein kinase in HIV type 1 production in vitro.
AB  - The proinflammatory cytokines interleukin (IL)-1 and tumor necrosis factor (TNF)
      promote HIV type 1 viral replication in vitro. In the present studies, HIV
      production was increased in the macrophagic U1 cell line expressing the HIV
      genome after exposure to IL-1beta, osmotic stress, or surface adhesion,
      suggesting a confluence of signaling pathways for proinflammatory cytokines and
      cell stressors. The p38 mitogen-activated protein kinase (MAPK) mediates both
      cytokine and stress responses; thus the role of this kinase in HIV production was
      investigated. HIV production as measured by p24 antigen correlated with changes
      in the expression of a specific (non-alpha) isoform of p38 MAPK. In the presence
      of a specific p38 MAPK inhibitor (p38 inh), IL-1beta-induced HIV production was
      suppressed by more than 90% and IL-1beta-induced IL-8 production was suppressed
      completely, both with IC50 of 0.01 microM. p38 inhibition blocked cell-associated
      p24 antigen and secreted virus to a similar extent. The p38 inh also decreased
      constitutive HIV production in freshly infected peripheral blood mononuclear
      cells by up to 50% (P < 0.05). Interruption of p38 MAPK activity represents a
      viable target for inhibition of HIV.

PMID- 9636166
TI  - A member of the Ran-binding protein family, Yrb2p, is involved in nuclear protein
      export.
AB  - Yeast cells mutated in YRB2, which encodes a nuclear protein with similarity to
      other Ran-binding proteins, fail to export nuclear export signal (NES)-containing
      proteins including HIV Rev out of the nucleus. Unlike Xpo1p/Crm1p/exportin, an
      NES receptor, Yrb2p does not shuttle between the nucleus and the cytoplasm but
      instead remains inside the nucleus. However, by both biochemical and genetic
      criteria, Yrb2p interacts with Xpo1p and not with other members of the
      importin/karyopherin beta superfamily. Moreover, the Yrb2p region containing
      nucleoporin-like FG repeats is important for NES-mediated protein export. Taken
      together, these data suggest that Yrb2p acts inside the nucleus to mediate the
      action of Xpo1p in at least one of several nuclear export pathways.

PMID- 9636167
TI  - Resistance gene N-mediated de novo synthesis and activation of a tobacco mitogen
      activated protein kinase by tobacco mosaic virus infection.
AB  - Salicylic acid-induced protein kinase (SIPK) and wounding-induced protein kinase
      (WIPK), two distinct members of the mitogen-activated protein (MAP) kinase
      family, are activated in tobacco resisting infection by tobacco mosaic virus
      (TMV). WIPK activation by TMV depends on the disease-resistance gene N because
      infection of susceptible tobacco not carrying the N gene failed to activate WIPK.
      Activation of WIPK required not only posttranslational phosphorylation but also a
      preceding rise in its mRNA and de novo synthesis of WIPK protein. The induction
      by TMV of WIPK mRNA and protein also occurred systemically. Its activation at the
      mRNA, protein, and enzyme levels was independent of salicylic acid. The
      regulation of WIPK at multiple levels by an N gene-mediated signal(s) suggests
      that this MAP kinase may be an important component upstream of salicylic acid in
      the signal-transduction pathway(s) leading to local and systemic resistance to
      TMV.

PMID- 9636168
TI  - Dissociation of cytokine-induced phosphorylation of Bad and activation of
      PKB/akt: involvement of MEK upstream of Bad phosphorylation.
AB  - The phosphatidylinositol 3-kinase (PI3K)-signaling pathway has emerged as an
      important component of cytokine-mediated survival of hemopoietic cells. Recently,
      the protein kinase PKB/akt (referred to here as PKB) has been identified as a
      downstream target of PI3K necessary for survival. PKB has also been implicated in
      the phosphorylation of Bad, potentially linking the survival effects of cytokines
      with the Bcl-2 family. We have shown that granulocyte/macrophage colony
      stimulating factor (GM-CSF) maintains survival in the absence of PI3K activity,
      and we now show that when PKB activation is also completely blocked, GM-CSF is
      still able to stimulate phosphorylation of Bad. Interleukin 3 (IL-3), on the
      other hand, requires PI3K for survival, and blocking PI3K partially inhibited Bad
      phosphorylation. IL-4, unique among the cytokines in that it lacks the ability to
      activate the p21ras-mitogen-activated protein kinase (MAPK) cascade, was found to
      activate PKB and promote cell survival, but it did not stimulate Bad
      phosphorylation. Finally, although our data suggest that the MAPK pathway is not
      required for inhibition of apoptosis, we provide evidence that phosphorylation of
      Bad may be occurring via a MAPK/ERK kinase (MEK)-dependent pathway. Together,
      these results demonstrate that although PI3K may contribute to phosphorylation of
      Bad in some instances, there is at least one other PI3K-independent pathway
      involved, possibly via activation of MEK. Our data also suggest that although
      phosphorylation of Bad may be one means by which cytokines can inhibit apoptosis,
      it may be neither sufficient nor necessary for the survival effect.

PMID- 9636169
TI  - Protein kinase mutants of human ATR increase sensitivity to UV and ionizing
      radiation and abrogate cell cycle checkpoint control.
AB  - In fission yeast, the rad3 gene product plays a critical role in sensing DNA
      structure defects and activating damage response pathways. A structural homologue
      of rad3 in humans (ATR) has been identified based on sequence similarity in the
      protein kinase domain. General information regarding ATR expression, protein
      kinase activity, and cellular localization is known, but its function in human
      cells remains undetermined. In the current study, the ATR protein was examined by
      gel filtration of protein extracts and was found to exist predominantly as part
      of a large protein complex. A kinase-inactivated form of the ATR gene was
      prepared by site-directed mutagenesis and was used in transfection experiments to
      probe the function of this complex. Introduction of this kinase-dead ATR into a
      normal fibroblast cell line, an ATM-deficient fibroblast line derived from a
      patient with ataxia-telangiectasia, or a p53 mutant cell line all resulted in
      significant losses in cell viability. Clones expressing the kinase-dead ATR
      displayed increased sensitivity to x-rays and UV and a loss of checkpoint
      control. We conclude that ATR functions as a critical part of a protein complex
      that mediates responses to ionizing and UV radiation in human cells. These
      responses include effects on cell viability and cell cycle checkpoint control.

PMID- 9636170
TI  - Human CUL1 forms an evolutionarily conserved ubiquitin ligase complex (SCF) with
      SKP1 and an F-box protein.
AB  - The SCF ubiquitin ligase complex of budding yeast triggers DNA replication by
      catalyzing ubiquitination of the S phase cyclin-dependent kinase inhibitor SIC1.
      SCF is composed of three proteins-ySKP1, CDC53 (Cullin), and the F-box protein
      CDC4-that are conserved from yeast to humans. As part of an effort to identify
      components and substrates of a putative human SCF complex, we isolated hSKP1 in a
      two-hybrid screen with hCUL1, the closest human homologue of CDC53. Here, we show
      that hCUL1 associates with hSKP1 in vivo and directly interacts with both hSKP1
      and the human F-box protein SKP2 in vitro, forming an SCF-like particle.
      Moreover, hCUL1 complements the growth defect of yeast cdc53(ts) mutants,
      associates with ubiquitination-promoting activity in human cell extracts, and can
      assemble into functional, chimeric ubiquitin ligase complexes with yeast SCF
      components. Taken together, these data suggest that hCUL1 functions as part of an
      SCF ubiquitin ligase complex in human cells. Further application of biochemical
      assays similar to those described here can now be used to identify
      regulators/components of hCUL1-based SCF complexes, to determine whether the
      hCUL2-hCUL5 proteins also are components of ubiquitin ligase complexes in human
      cells, and to screen for chemical compounds that modulate the activities of the
      hSKP1 and hCUL1 proteins.

PMID- 9636171
TI  - Nuclear-cytoplasmic shuttling of C-ABL tyrosine kinase.
AB  - The ubiquitously expressed nonreceptor tyrosine kinase c-Abl contains three
      nuclear localization signals, however, it is found in both the nucleus and the
      cytoplasm of proliferating fibroblasts. A rapid and transient loss of c-Abl from
      the nucleus is observed upon the initial adhesion of fibroblasts onto a
      fibronectin matrix, suggesting the possibility of nuclear export [Lewis, J.,
      Baskaran, R. , Taagepera, S., Schwartz, M. & Wang, J. (1996) Proc. Natl. Acad.
      Sci. USA 93, 15174-15179]. Here we show that the C terminus of c-Abl does indeed
      contain a functional nuclear export signal (NES) with the characteristic leucine
      rich motif. The c-Abl NES can functionally complement an NES-defective HIV Rev
      protein (RevDelta3NI) and can mediate the nuclear export of glutathione-S
      transferase. The c-Abl NES function is sensitive to the nuclear export inhibitor
      leptomycin B. Mutation of a single leucine (L1064A) in the c-Abl NES abrogates
      export function. The NES-mutated c-Abl, termed c-Abl NES(-), is localized
      exclusively to the nucleus. Treatment of cells with leptomycin B also leads to
      the nuclear accumulation of wild-type c-Abl protein. The c-Abl NES(-) is not lost
      from the nucleus when detached fibroblasts are replated onto fibronectin matrix.
      Taken together, these results demonstrate that c-Abl shuttles continuously
      between the nucleus and the cytoplasm and that the rate of nuclear import and
      export can be modulated by the adherence status of fibroblastic cells.

PMID- 9636172
TI  - A chloroplast processing enzyme functions as the general stromal processing
      peptidase.
AB  - A highly specific stromal processing activity is thought to cleave a large
      diversity of precursors targeted to the chloroplast, removing an N-terminal
      transit peptide. The identity of this key component of the import machinery has
      not been unequivocally established. We have previously characterized a
      chloroplast processing enzyme (CPE) that cleaves the precursor of the light
      harvesting chlorophyll a/b binding protein of photosystem II (LHCPII). Here we
      report the overexpression of active CPE in Escherichia coli. Examination of the
      recombinant enzyme in vitro revealed that it cleaves not only preLHCPII, but also
      the precursors for an array of proteins essential for different reactions and
      destined for different compartments of the organelle. CPE also processes its own
      precursor in trans. Neither the recombinant CPE nor the native CPE of
      chloroplasts process a preLHCPII mutant with an altered cleavage site
      demonstrating that both forms of the enzyme are sensitive to the same structural
      modification of the substrate. The transit peptide of the precursor of ferredoxin
      is released by a single cleavage event and found intact after processing by
      recombinant CPE and a chloroplast extract as well. These results provide the
      first direct demonstration that CPE is the general stromal processing peptidase
      that acts as an endopeptidase. Significantly, recombinant CPE cleaves in the
      absence of other chloroplast proteins, and this activity depends on metal
      cations, such as zinc.

PMID- 9636173
TI  - Masking and unmasking of the sialic acid-binding lectin activity of CD22 (Siglec
      2) on B lymphocytes.
AB  - CD22 is a B cell-restricted glycoprotein involved in signal transduction and
      modulation of cellular activation. It is also an I-type lectin (now designated
      Siglec-2), whose extracellular domain can specifically recognize alpha2-6-linked
      sialic acid (Sia) residues. This activity is postulated to mediate intercellular
      adhesion and/or to act as a coreceptor in antigen-induced B cell activation.
      However, studies with recombinant CD22 indicate that the lectin function can be
      inactivated by expression of alpha2-6-linked Sia residues on the same cell
      surface. To explore whether this masking phenomenon affects native CD22 on B
      cells, we first developed a probe to detect the lectin activity of recombinant
      CD22 expressed on Chinese hamster ovary cells (which have no endogenous alpha2-6
      linked Sia residues). This probe is inactive against CD22-positive B lymphoma
      cells and Epstein-Barr virus-transformed lymphoblasts which express high levels
      of alpha2-6-linked Sia residues. Enzymatic desialylation unmasks the CD22 lectin
      activity, indicating that endogenous Sia residues block the CD22 lectin-binding
      site. Truncation of the side chains of cell surface Sia residues by mild
      periodate oxidation (known to abrogate Sia recognition by CD22) also had this
      unmasking effect, indicating that the effects of desialylation are not due to a
      loss of negative charge. Normal resting B cells from human peripheral blood gave
      similar findings. However, the lectin is partially unmasked during in vitro
      activation of these cells. Thus, the lectin activity of CD22 is restricted by
      endogenous sialylation in resting B cells and may be transiently unmasked during
      in vivo activation, perhaps to modulate intercellular or intracellular
      interactions at this critical stage in the humoral response.

PMID- 9636174
TI  - Mitogenic and oncogenic properties of the small G protein Rap1b.
AB  - It has been widely reported that the small GTP-binding protein Rap1 has an anti
      Ras and anti-mitogenic activity. Thus, it is generally accepted that a normal
      physiological role of Rap1 proteins is to antagonize Ras mitogenic signals,
      presumably by forming nonproductive complexes with proteins that are typically
      effectors or modulators of Ras. Rap1 is activated by signals that raise
      intracellular levels of cAMP, a molecule that has long been known to exert both
      inhibitory and stimulatory effects on cell growth. We have now tested the
      intriguing hypothesis that Rap1 could have mitogenic effects in systems in which
      cAMP stimulates cell proliferation. The result of experiments addressing this
      possibility revealed that Rap1 has full oncogenic potential. Expression of Rap1
      in these cells results in a decreased doubling time, an increased saturation
      density, and an unusual anchorage-dependent morphological transformation. Most
      significantly, however, Rap1-expressing cells formed tumors when injected into
      nude mice. Thus, we propose that the view that holds Rap1 as an antimitogenic
      protein should be restricted and conclude that Rap1 is a conditional oncoprotein.

PMID- 9636175
TI  - Phosphorylation of histone H3 at serine 10 is correlated with chromosome
      condensation during mitosis and meiosis in Tetrahymena.
AB  - H3 phosphorylation has been correlated with mitosis temporally in mammalian cells
      and spatially in ciliated protozoa. In logarithmically growing Tetrahymena
      thermophila cells, for example, H3 phosphorylation can be detected in germline
      micronuclei that divide mitotically but not in somatic macronuclei that divide
      amitotically. Here, we demonstrate that micronuclear H3 phosphorylation occurs at
      a single site (Ser-10) in the amino-terminal domain of histone H3, the same site
      phosphorylated during mitosis in mammalian cells. Using an antibody specific for
      Ser-10 phosphorylated H3, we show that, in Tetrahymena, this modification is
      correlated with mitotic and meiotic divisions of micronuclei in a fashion that
      closely coincides with chromosome condensation. Our data suggest that H3
      phosphorylation at Ser-10 is a highly conserved event among eukaryotes and is
      likely involved in both mitotic and meiotic chromosome condensation.

PMID- 9636176
TI  - A phenotype-based screen for embryonic lethal mutations in the mouse.
AB  - The genetic pathways that control development of the early mammalian embryo have
      remained poorly understood, in part because the systematic mutant screens that
      have been so successful in the identification of genes and pathways that direct
      embryonic development in Drosophila, Caenorhabditis elegans, and zebrafish have
      not been applied to mammalian embryogenesis. Here we demonstrate that chemical
      mutagenesis with ethylnitrosourea can be combined with the resources of mouse
      genomics to identify new genes that are essential for mammalian embryogenesis. A
      pilot screen for abnormal morphological phenotypes of midgestation embryos
      identified five mutant lines; the phenotypes of four of the lines are caused by
      recessive traits that map to single regions of the genome. Three mutant lines
      display defects in neural tube closure: one is caused by an allele of the open
      brain (opb) locus, one defines a previously unknown locus, and one has a complex
      genetic basis. Two mutations produce novel early phenotypes and map to regions of
      the genome not previously implicated in embryonic patterning.

PMID- 9636177
TI  - Retardation of skeletal development and cervical abnormalities in transgenic mice
      expressing a dominant-negative retinoic acid receptor in chondrogenic cells.
AB  - Skeletal formation is a fundamental element of body patterning and is strictly
      regulated both temporally and spatially by a variety of molecules. Among these,
      retinoic acid (RA) has been shown to be involved in normal skeletal development.
      However, its pleiotropic effects have caused difficulty in identifying its
      crucial target cells and molecular mechanisms for each effect. Development of
      cartilage primordia is an important process in defining the skeletal structures.
      To address the role of RA in skeletal formation, we have generated mice
      expressing a dominant-negative retinoic acid receptor (RAR) in chondrogenic cells
      by using the type II collagen alpha1 promoter, and we have analyzed their
      phenotypes. These mice exhibited small cartilage primordia during development and
      retarded skeletal formation in both embryonic and postnatal periods. They also
      showed selective degeneration in their cervical vertebrae combined with homeotic
      transformations, but not in their extremities. The cervical phenotypes are
      reminiscent of phenotypes involving homeobox genes. We found that the expression
      of Hoxa-4 was indeed reduced in the cartilage primordia of cervical vertebrae of
      embryonic day 12.5 embryos. These observations demonstrate that endogenous RA
      acts directly on chondrogenic cells to promote skeletal growth in both embryonic
      and growing periods, and it regulates the proper formation of cervical vertebrae.
      Furthermore, RA apparently specifies the identities of the cervical vertebrae
      through the regulation of homeobox genes in the chondrogenic cells. Great
      similarities of the phenotypes between our mice and reported RAR knockout mice
      revealed that chondrogenic cells are a principal RA target during complex
      cascades of skeletal development.

PMID- 9636178
TI  - Higher temporal variability of forest breeding bird communities in fragmented
      landscapes.
AB  - Understanding the relationship between animal community dynamics and landscape
      structure has become a priority for biodiversity conservation. In particular,
      predicting the effects of habitat destruction that confine species to networks of
      small patches is an important prerequisite to conservation plan development.
      Theoretical models that predict the occurrence of species in fragmented
      landscapes, and relationships between stability and diversity do exist. However,
      reliable empirical investigations of the dynamics of biodiversity have been
      prevented by differences in species detection probabilities among landscapes.
      Using long-term data sampled at a large spatial scale in conjunction with a
      capture-recapture approach, we developed estimates of parameters of community
      changes over a 22-year period for forest breeding birds in selected areas of the
      eastern United States. We show that forest fragmentation was associated not only
      with a reduced number of forest bird species, but also with increased temporal
      variability in the number of species. This higher temporal variability was
      associated with higher local extinction and turnover rates. These results have
      major conservation implications. Moreover, the approach used provides a practical
      tool for the study of the dynamics of biodiversity.

PMID- 9636179
TI  - Identification of novel susceptibility loci for inflammatory bowel disease on
      chromosomes 1p, 3q, and 4q: evidence for epistasis between 1p and IBD1.
AB  - The idiopathic inflammatory bowel diseases, Crohn's disease (CD) and ulcerative
      colitis (UC), are chronic, frequently disabling diseases of the intestines.
      Segregation analyses, twin concordance, and ethnic differences in familial risks
      have established that CD and UC are complex, non-Mendelian, related genetic
      disorders. We performed a genome-wide screen using 377 autosomal markers, on 297
      CD, UC, or mixed relative pairs from 174 families, 37% Ashkenazim. We observed
      evidence for linkage at 3q for all families (multipoint logarithm of the odds
      score (MLod) = 2.29, P = 5.7 x 10(-4)), with greatest significance for non
      Ashkenazim Caucasians (MLod = 3.39, P = 3.92 x 10(-5)), and at chromosome 1p
      (MLod = 2.65, P = 2.4 x 10(-4)) for all families. In a limited subset of mixed
      families (containing one member with CD and another with UC), evidence for
      linkage was observed on chromosome 4q (MLod = 2.76, P = 1.9 x 10(-4)), especially
      among Ashkenazim. There was confirmatory evidence for a CD locus, overlapping
      IBD1, in the pericentromeric region of chromosome 16 (MLod = 1.69, P = 2.6 x 10(
      3)), particularly among Ashkenazim (MLod = 1.51, P = 7.8 x 10(-3)); however,
      positive MLod scores were observed over a very broad region of chromosome 16.
      Furthermore, evidence for epistasis between IBD1 and chromosome 1p was observed.
      Thirteen additional loci demonstrated nominal (MLod > 1.0, P < 0.016) evidence
      for linkage. This screen provides strong evidence that there are several major
      susceptibility loci contributing to the genetic risk for CD and UC.

PMID- 9636180
TI  - Transdominant genetic analysis of a growth control pathway.
AB  - Genetic selections that use proteinaceous transdominant inhibitors encoded by DNA
      libraries to cause mutant phenocopies may facilitate genetic analysis in
      traditionally nongenetic organisms. We performed a selection for random short
      peptides and larger protein fragments (collectively termed "perturbagens") that
      inhibit the yeast pheromone response pathway. Peptide and protein fragment
      perturbagens that permit cell division in the presence of pheromone were
      recovered. Two perturbagens were derived from proteins required for pheromone
      response, and an additional two were derived from proteins that may negatively
      influence the pheromone response pathway. Furthermore, three known components of
      the pathway were identified as probable perturbagen targets based on physical
      interaction assays. Thus, by selection for transdominant inhibitors of pheromone
      response, multiple pathway components were identified either directly as gene
      fragments or indirectly as the likely targets of specific perturbagens. These
      results, combined with the results of previous work [Holzmayer, T. A., Pestov, D.
      G. & Roninson, I. B. (1992) Nucl. Acids. Res. 20, 711-717; Whiteway, M., Dignard,
      D. & Thomas, D. Y. (1992) Proc. Natl. Acad. Sci. USA 89, 9410-9414; and Gudkov,
      A. V., Kazarov, A. R., Thimmapaya, R., Axenovich, S. A., Mazo, I. A. & Roninson,
      I. B. (1994) Proc. Natl. Acad. Sci. USA 91, 3744-3748], suggest that
      transdominant genetic analysis of the type described here will be broadly
      applicable.

PMID- 9636181
TI  - Computerized polymorphic marker identification: experimental validation and a
      predicted human polymorphism catalog.
AB  - A computational system for the prediction of polymorphic loci directly and
      efficiently from human genomic sequence was developed and verified. A suite of
      programs, collectively called POMPOUS (polymorphic marker prediction of
      ubiquitous simple sequences) detects tandem repeats ranging from dinucleotides up
      to 250 mers, scores them according to predicted level of polymorphism, and
      designs appropriate flanking primers for PCR amplification. This approach was
      validated on an approximately 750-kilobase region of human chromosome 3p21.3,
      involved in lung and breast carcinoma homozygous deletions. Target DNA from 36
      paired B lymphoblastoid and lung cancer lines was amplified and allelotyped for
      33 loci predicted by POMPOUS to be variable in repeat size. We found that among
      those 36 predominately Caucasian individuals 22 of the 33 (67%) predicted loci
      were polymorphic with an average heterozygosity of 0.42. Allele loss in this
      region was found in 27/36 (75%) of the tumor lines using these markers. POMPOUS
      provides the genetic researcher with an additional tool for the rapid and
      efficient identification of polymorphic markers, and through a World Wide Web
      site, investigators can use POMPOUS to identify polymorphic markers for their
      research. A catalog of 13,261 potential polymorphic markers and associated primer
      sets has been created from the analysis of 141,779,504 base pairs of human
      genomic sequence in GenBank. This data is available on our Web site
      (pompous.swmed.edu) and will be updated periodically as GenBank is expanded and
      algorithm accuracy is improved.

PMID- 9636182
TI  - The lepidopteran transposon vector, piggyBac, mediates germ-line transformation
      in the Mediterranean fruit fly.
AB  - The piggyBac (IFP2) short inverted terminal repeat transposable element from the
      cabbage looper Trichoplusia ni was tested for gene transfer vector function as
      part of a bipartite vector-helper system in the Mediterranean fruit fly Ceratitis
      capitata. A piggyBac vector marked with the medfly white gene was tested with a
      normally regulated piggyBac transposase helper at two different concentrations in
      a white eye host strain. Both experiments yielded transformants at an approximate
      frequency of 3-5%, with a total of six lines isolated having pigmented eyes with
      various levels of coloration. G1 transformant siblings from each line shared at
      least one common integration, with several sublines having an additional second
      integration. For the first transformant line isolated, two integrations were
      determined to be stable for 15 generations. For five of the lines, a piggyBac
      mediated transposition was verified by sequencing the insertion site junctions
      isolated by inverse PCR that identified a characteristic piggyBac TTAA target
      site duplication. The efficient and stable transformation of the medfly with a
      lepidopteran vector represents transposon function over a relatively large
      evolutionary distance and suggests that the piggyBac system will be functional in
      a broad range of insects.

PMID- 9636183
TI  - Fission yeast orb6, a ser/thr protein kinase related to mammalian rho kinase and
      myotonic dystrophy kinase, is required for maintenance of cell polarity and
      coordinates cell morphogenesis with the cell cycle.
AB  - The molecular mechanisms that coordinate cell morphogenesis with the cell cycle
      remain largely unknown. We have investigated this process in fission yeast where
      changes in polarized cell growth are coupled with cell cycle progression. The
      orb6 gene is required during interphase to maintain cell polarity and encodes a
      serine/threonine protein kinase, belonging to the myotonic dystrophy
      kinase/cot1/warts family. A decrease in Orb6 protein levels leads to loss of
      polarized cell shape and to mitotic advance, whereas an increase in Orb6 levels
      maintains polarized growth and delays mitosis by affecting the p34(cdc2) mitotic
      kinase. Thus the Orb6 protein kinase coordinates maintenance of cell polarity
      during interphase with the onset of mitosis. orb6 interacts genetically with
      orb2, which encodes the Pak1/Shk1 protein kinase, a component of the Ras1 and
      Cdc42-dependent signaling pathway. Our results suggest that Orb6 may act
      downstream of Pak1/Shk1, forming part of a pathway coordinating cell
      morphogenesis with progression through the cell cycle.

PMID- 9636184
TI  - Su(UR)ES: a gene suppressing DNA underreplication in intercalary and pericentric
      heterochromatin of Drosophila melanogaster polytene chromosomes.
AB  - A genetic locus suppressing DNA underreplication in intercalary heterochromatin
      (IH) and pericentric heterochromatin (PH) of the polytene chromosomes of
      Drosophila melanogaster salivary glands, has been described. Found in the
      In(1)scV2 strain, the mutation, designated as Su(UR)ES, was located on chromosome
      3L at position 34. 8 and cytologically mapped to region 68A3-B4. A cytological
      phenotype was observed in the salivary gland chromosomes of larvae homozygous and
      hemizygous for Su(UR)ES: (i) in the IH regions, that normally are incompletely
      polytenized and so they often break to form "weak points," underreplication is
      suppressed, breaks and ectopic contacts disappear; (ii) the degree of
      polytenization in PH grows higher. That is why the regions in chromosome arm
      basements, normally beta-heterochromatic, acquire a distinct banding pattern, i.
      e., become euchromatic by morphological criteria; (iii) an additional bulk of
      polytenized material arises between the arms of chromosome 3 to form a fragment
      with a typical banding pattern. Chromosome 2 PH reveals additional alpha
      heterochromatin. Su(UR)ES does not affect the viability, fertility, or
      morphological characters of the imago, and has semidominant expression in the
      heterozygote and distinct maternal effect. The results obtained provide evidence
      that the processes leading to DNA underreplication in IH and PH are affected by
      the same genetic mechanism.

PMID- 9636185
TI  - Transfer of human serum IgG to nonobese diabetic Igmu null mice reveals a role
      for autoantibodies in the loss of secretory function of exocrine tissues in
      Sjogren's syndrome.
AB  - The NOD (nonobese diabetic) mouse has been studied as an animal model for
      autoimmune insulin-dependent diabetes and Sjogren's syndrome. NOD.Igmu null mice,
      which lack functional B lymphocytes, develop progressive histopathologic lesions
      of the submandibular and lachrymal glands similar to NOD mice, but in the absence
      of autoimmune insulitis and diabetes. Despite the focal appearance of T cells in
      salivary and lachrymal tissues, NOD.Igmu null mice fail to lose secretory
      function as determined by stimulation of the muscarinic/cholinergic receptor by
      the agonist pilocarpine, suggesting a role for B cell autoantibodies in mediating
      exocrine dryness. Infusion of purified serum IgG or F(ab')2 fragments from
      parental NOD mice or human primary Sjogren's syndrome patients, but not serum IgG
      from healthy controls, alters stimulated saliva production, an observation
      consistent with antibody binding to neural receptors. Furthermore, human patient
      IgG fractions competitively inhibited the binding of the muscarinic receptor
      agonist, [3H]quinuclidinyl benzilate, to salivary gland membranes. This
      autoantibody activity is lost after preadsorption with intact salivary cells.
      These findings indicate that autoantibodies play an important part in the
      functional impairment of secretory processes seen in connection with the
      autoimmune exocrinopathy of Sjogren's syndrome.

PMID- 9636186
TI  - Extracellular enveloped vaccinia virus is resistant to complement because of
      incorporation of host complement control proteins into its envelope.
AB  - Vaccinia virus (VV) produces two antigenically and structurally distinct
      infectious virions, intracellular mature virus (IMV) and extracellular enveloped
      virus (EEV). Here we have investigated the resistance of EEV and IMV to
      neutralization by complement in the absence of immune antibodies. When EEV is
      challenged with complement from the same species as the cells used to grow the
      virus, EEV is resistant to neutralization by complement, whereas IMV is not. EEV
      resistance was not a result of EEV protein B5R, despite its similarity to
      proteins of the regulators of complement activation (RCA) family, or to any of
      the other EEV proteins tested (A34R, A36R, and A56R gene products). EEV was
      sensitive to complement when the virus was grown in one species and challenged
      with complement from a different species, suggesting that complement resistance
      might be mediated by host RCA incorporated into the EEV outer envelope. This
      hypothesis was confirmed by several observations: (i) immunoblot analysis
      revealed that cellular membrane proteins CD46, CD55, CD59, CD71, CD81, and major
      histocompatibility complex class I antigen were detected in purified EEV but not
      IMV; (ii) immunoelectron microscopy revealed cellular RCA on the surface of EEV
      retained on the cell surface; and (iii) EEV derived from rat cells expressing the
      human RCA CD55 or CD55 and CD59 were more resistant to human complement than EEV
      derived from control rat cells that expressed neither CD55 nor CD59. These data
      justify further analysis of the roles of these (and possible other) cellular
      proteins in EEV biology.

PMID- 9636187
TI  - Tropomyosin implicated in host protective responses to microfilariae in
      onchocerciasis.
AB  - A cDNA from adult female Onchocerca volvulus encoding the C-terminal portion of a
      tropomyosin isoform (termed MOv-14) has been shown previously to confer
      protective immunity in rodent models of onchocerciasis. The full-length sequence
      (designated Ov-tmy-1) obtained by PCR amplification, codes for a protein of 33
      kDa and shares 91% identity with tropomyosins from other nematodes, falling to
      57% identity with human alpha-tropomyosin. Ov-TMY-1 migrates with an apparent
      molecular mass of 42 kDa on SDS/PAGE and is present in all life-cycle stages, as
      determined by immunoblotting. Immunogold electron microscopy identified antigenic
      sites within muscle blocks and the cuticle of microfilariae and infective larvae.
      Anti-MOv14 antibodies were abundant in mice exhibiting serum-transferable
      protection against microfilariae conferred by vaccination with a PBS-soluble
      parasite extract. In contrast, little or no MOv14-specific antibody was present
      in mice inoculated with live microfilariae, in which resistance is mediated by
      antibody-independent mechanisms. In human infections, there was an inverse
      correlation between anti-tropomyosin IgG levels and densities of microfilariae in
      the skin. Seropositivity varied with the relative endemicity of infection. An
      immunodominant B cell epitope within Ov-TMY-1 (AQLLAEEADRKYD) was mapped to the N
      terminus of the MOv14 protein by using sera from protectively vaccinated mice.
      Intriguingly, the sequence coincides with an IgE-binding epitope within shrimp
      tropomyosin, believed to be responsible for hypersensitivity in individuals
      exhibiting allergy to shellfish. IgG and IgE antibodies reacting with the O.
      volvulus epitope were detected in human infections. It is concluded that antibody
      responses to tropomyosin may be important in limiting microfilarial densities in
      a proportion of individuals with onchocerciasis and have the potential to mediate
      hypersensitivity reactions to dead microfilariae, raising the possibility of a
      link with the immunopathology of infection.

PMID- 9636188
TI  - Demonstration of an interferon gamma-dependent tumor surveillance system in
      immunocompetent mice.
AB  - This study demonstrates that endogenously produced interferon gamma (IFN-gamma)
      forms the basis of a tumor surveillance system that controls development of both
      chemically induced and spontaneously arising tumors in mice. Compared with wild
      type mice, mice lacking sensitivity to either IFN-gamma (i.e., IFN-gamma receptor
      deficient mice) or all IFN family members (i.e., Stat1-deficient mice) developed
      tumors more rapidly and with greater frequency when challenged with different
      doses of the chemical carcinogen methylcholanthrene. In addition, IFN-gamma
      insensitive mice developed tumors more rapidly than wild-type mice when bred onto
      a background deficient in the p53 tumor-suppressor gene. IFN-gamma-insensitive
      p53(-/-) mice also developed a broader spectrum of tumors compared with mice
      lacking p53 alone. Using tumor cells derived from methylcholanthrene-treated IFN
      gamma-insensitive mice, we found IFN-gamma's actions to be mediated at least
      partly through its direct effects on the tumor cell leading to enhanced tumor
      cell immunogenicity. The importance and generality of this system is evidenced by
      the finding that certain types of human tumors become selectively unresponsive to
      IFN-gamma. Thus, IFN-gamma forms the basis of an extrinsic tumor-suppressor
      mechanism in immunocompetent hosts.

PMID- 9636189
TI  - Optimal selectin-mediated rolling of leukocytes during inflammation in vivo
      requires intercellular adhesion molecule-1 expression.
AB  - Leukocyte interactions with vascular endothelium during inflammation occur
      through discrete steps involving selectin-mediated leukocyte rolling and
      subsequent firm adhesion mediated by members of the integrin and Ig families of
      adhesion molecules. To identify functional synergy between selectin and Ig family
      members, mice deficient in both L-selectin and intercellular adhesion molecule 1
      (ICAM-1) were generated. Leukocyte rolling velocities in cremaster muscle venules
      were increased significantly in ICAM-1-deficient mice during both trauma- and
      tumor necrosis factor alpha-induced inflammation, but rolling leukocyte flux was
      not reduced. Elimination of ICAM-1 expression in L-selectin-deficient mice
      resulted in a sharp reduction in the flux of rolling leukocytes during tumor
      necrosis factor alpha-induced inflammation. The observed differences in leukocyte
      rolling behavior demonstrated that ICAM-1 expression was required for optimal P-
      and L-selectin-mediated rolling. Increased leukocyte rolling velocities
      presumably translated into decreased tissue emigration because circulating
      neutrophil, monocyte, and lymphocyte numbers were increased markedly in L
      selectin/ICAM-1-deficient mice. Furthermore, neutrophil emigration during acute
      peritonitis was reduced by 80% in the double-deficient mice compared with either
      L-selectin or ICAM-1-deficient mice. Thus, members of the selectin and Ig
      families function synergistically to mediate optimal leukocyte rolling in vivo,
      which is essential for the generation of effective inflammatory responses.

PMID- 9636190
TI  - Direct visualization of antigen-specific T cells: HTLV-1 Tax11-19- specific
      CD8(+) T cells are activated in peripheral blood and accumulate in cerebrospinal
      fluid from HAM/TSP patients.
AB  - Human T lymphotropic virus type 1 (HTLV-1) -associated myelopathy/tropic spastic
      paraparesis is a demyelinating inflammatory neurologic disease associated with
      HTLV-1 infection. HTLV-1 Tax11-19-specific cytotoxic T cells have been isolated
      from HLA-A2-positive patients. We have used a peptide-loaded soluble HLA-A2-Ig
      complex to directly visualize HTLV-1 Tax11-19-specific T cells from peripheral
      blood and cerebrospinal fluid without in vitro stimulation. Five of six HTLV-1
      associated myelopathy/tropic spastic paraparesis patients carried a significant
      number (up to 13.87%) of CD8(+) lymphocytes specific for the HTLV-1 Tax11-19
      peptide in their peripheral blood, which were not found in healthy controls.
      Simultaneous comparison of peripheral blood and cerebrospinal fluid from one
      patient revealed 2.5-fold more Tax11-19-specific T cells in the cerebrospinal
      fluid (23.7% vs. 9.4% in peripheral blood lymphocyte). Tax11-19-specific T cells
      were seen consistently over a 9-yr time course in one patient as far as 19 yrs
      after the onset of clinical symptoms. Further analysis of HTLV-1 Tax11-19
      specific CD8(+) T lymphocytes in HAM/TSP patients showed different expression
      patterns of activation markers, intracellular TNF-alpha and gamma-interferon
      depending on the severity of the disease. Thus, visualization of antigen-specific
      T cells demonstrates that HTLV-1 Tax11-19-specific CD8(+) T cells are activated,
      persist during the chronic phase of the disease, and accumulate in cerebrospinal
      fluid, showing their pivotal role in the pathogenesis of this neurologic disease.

PMID- 9636191
TI  - Definition of MHC and T cell receptor contacts in the HLA-DR4restricted
      immunodominant epitope in type II collagen and characterization of collagen
      induced arthritis in HLA-DR4 and human CD4 transgenic mice.
AB  - Rheumatoid arthritis (RA) is an autoimmune disease associated with the HLA-DR4
      and DR1 alleles. The target autoantigen(s) in RA is unknown, but type II collagen
      (CII) is a candidate, and the DR4- and DR1-restricted immunodominant T cell
      epitope in this protein corresponds to amino acids 261-273 (CII 261-273). We have
      defined MHC and T cell receptor contacts in CII 261-273 and provide strong
      evidence that this peptide corresponds to the peptide binding specificity
      previously found for RA-associated DR molecules. Moreover, we demonstrate that
      HLA-DR4 and human CD4 transgenic mice homozygous for the I-Abbeta0 mutation are
      highly susceptible to collagen-induced arthritis and describe the clinical course
      and histopathological changes in the affected joints.

PMID- 9636192
TI  - Resistance to endotoxic shock and reduced neutrophil migration in mice deficient
      for the Src-family kinases Hck and Fgr.
AB  - Signal transduction through the leukocyte integrins is required for the processes
      of firm adhesion, activation, and chemotaxis of neutrophils during inflammatory
      reactions. Neutrophils isolated from knockout mice that are deficient in the
      expression of p59/61(hck) (Hck) and p58(c-fgr) (Fgr), members of the Src-family
      of protein tyrosine kinases, have been shown to be defective in adhesion mediated
      activation. Cells from these animals have impaired induction of respiratory burst
      and granule secretion following plating on surfaces that crosslink beta2 and
      beta3 integrins. To determine if the defective function of hck-/-fgr-/-
      neutrophils observed in vitro also results in impaired inflammatory responses in
      vivo, we examined responses induced by lipopolysaccharide (LPS) injection in
      these animals. The hck-/-fgr-/- mice showed marked resistance to the lethal
      effects of high-dose LPS injection despite the fact that high levels of serum
      tumor necrosis factor alpha and interleukin 1alpha were detected. Serum chemistry
      analysis revealed a marked reduction in liver and renal damage in mutant mice
      treated with LPS, whereas blood counts showed a marked neutrophilia that was not
      seen in wild-type animals. Direct examination of liver sections from mutant mice
      revealed reduced neutrophil migration into the tissue. These data demonstrate
      that defective integrin signaling in neutrophils, caused by loss of Hck and Fgr
      tyrosine kinase activity, results in impaired inflammation-dependent tissue
      injury in vivo.

PMID- 9636193
TI  - Low-dose expression of a human apolipoprotein E transgene in macrophages restores
      cholesterol efflux capacity of apolipoprotein E-deficient mouse plasma.
AB  - Apolipoprotein E- (apoE) deficient (E-/-) mice develop severe hyperlipidemia and
      diffuse atherosclerosis. Low-dose expression of a human apoE3 transgene in
      macrophages of apoE-deficient mice (E-/-hTgE+/0), which results in about 5% of
      wild-type apoE plasma levels, did not correct hyperlipidemia but significantly
      reduced the extent of atherosclerotic lesions. To investigate the contribution of
      apoE to reverse cholesterol transport, we compared plasmas of wild-type (E+/+), E
      /-, and E-/-hTgE+/0 mice for the appearance of apoE-containing lipoproteins by
      electrophoresis and their capacity to take up and esterify 3H-labeled cholesterol
      from radiolabeled fibroblasts or J774 macrophages. Wild-type plasma displayed
      lipoproteins containing apoE that were the size of high density lipoprotein and
      that had either electrophoretic alpha or gamma mobilities. Similar particles were
      also present in E-/-hTgE+/0 plasma. Depending on incubation time, E-/- plasma
      released 48-74% less 3H-labeled cholesterol from fibroblasts than E+/+ plasma,
      whereas cholesterol efflux into E-/-hTgE+/0 plasma was only 11-25% lower than
      into E+/+ plasma. E-/-hTgE+/0 plasma also released 10% more 3H-labeled
      cholesterol from radiolabeled J774 macrophages than E-/- plasma. E+/+ and E-/
      hTgE+/0 plasma each esterified significantly more cell-derived 3H-labeled
      cholesterol than E-/- plasma. Moreover, E-/- plasma accumulated much smaller
      proportions of fibroblast-derived 3H-labeled cholesterol in fractions with
      electrophoretic gamma and alpha mobility than E+/+ and E-/-hTgE+/0 plasma. Thus,
      low-dose expression of apoE in macrophages nearly restored the cholesterol efflux
      capacity of apoE-deficient plasma through the formation of apoE-containing
      particles, which efficiently take up cell-derived cholesterol, and through the
      increase of cholesterol esterification activity. Thus, macrophage-derived apoE
      may protect against atherosclerosis by increasing cholesterol efflux from
      arterial wall cells.

PMID- 9636194
TI  - Tissue factor gene expression in the adipose tissues of obese mice.
AB  - Altered expression of proteins of the fibrinolytic and coagulation cascades in
      obesity may contribute to the cardiovascular risk associated with this condition.
      We previously reported that plasminogen activator inhibitor 1 (PAI-1) is
      dramatically up-regulated in the plasma and adipose tissues of genetically obese
      mice. This change may disturb normal hemostatic balance and create a severe
      hypofibrinolytic state. Here we show that tissue factor (TF) gene expression also
      is significantly elevated in the epididymal and subcutaneous fat pads from ob/ob
      mice compared with their lean counterparts, and that its level of expression in
      obese mice increases with age and the degree of obesity. Cell fractionation and
      in situ hybridization analysis of adipose tissues indicate that TF mRNA is
      increased in adipocytes and in unidentified stromal vascular cells. Transforming
      growth factor beta (TGF-beta) is known to be elevated in the adipose tissue of
      obese mice, and administration of TGF-beta increased TF mRNA expression in
      adipocytes in vivo and in vitro. These observations raise the possibility that TF
      and TGF-beta may contribute to the increased cardiovascular disease that
      accompanies obesity and related non-insulin-dependent diabetes mellitus, and that
      the adipocyte plays a key role in this process. The recent demonstration that TF
      also influences angiogenesis, cell adhesion, and signaling suggests that its
      exact role in adipose tissue physiology/pathology, may be complex.

PMID- 9636195
TI  - Prothrombin deficiency results in embryonic and neonatal lethality in mice.
AB  - The conversion of prothrombin (FII) to the serine protease, thrombin (FIIa), is a
      key step in the coagulation cascade because FIIa triggers platelet activation,
      converts fibrinogen to fibrin, and activates regulatory pathways that both
      promote and ultimately suppress coagulation. However, several observations
      suggest that FII may serve a broader physiological role than simply stemming
      blood loss, including the identification of multiple G protein-coupled, thrombin
      activated receptors, and the well-documented mitogenic activity of FIIa in in
      vitro test systems. To explore in greater detail the physiological roles of FII
      in vivo, FII-deficient (FII-/-) mice were generated. Inactivation of the FII gene
      leads to partial embryonic lethality with more than one-half of the FII-/-
      embryos dying between embryonic days 9.5 and 11.5. Bleeding into the yolk sac
      cavity and varying degrees of tissue necrosis were observed in many FII-/-
      embryos within this gestational time frame. However, at least one-quarter of the
      FII-/- mice survived to term, but ultimately they, too, developed fatal
      hemorrhagic events and died within a few days of birth. This study directly
      demonstrates that FII is important in maintaining vascular integrity during
      development as well as postnatal life.

PMID- 9636196
TI  - Incomplete embryonic lethality and fatal neonatal hemorrhage caused by
      prothrombin deficiency in mice.
AB  - Deficiency of blood coagulation factor V or tissue factor causes the death of
      mouse embryos by 10.5 days of gestation, suggesting that part of the blood
      coagulation system is necessary for development. This function is proposed to
      require either generation of the serine protease thrombin and cell signaling
      through protease-activated receptors or an activity of tissue factor that is
      distinct from blood clotting. We find that murine deficiency of prothrombin
      clotting factor 2 (Cf2) was associated with the death of approximately 50% of
      Cf2(-/-) embryos by embryonic day 10.5 (E10.5), and surviving embryos had
      characteristic defects in yolk sac vasculature. Most of the remaining Cf2(-/-)
      embryos died by E15.5, but those surviving to E18.5 appeared normal. The rare
      Cf2(-/-) neonates died of hemorrhage on the first postnatal day. These studies
      suggest that a part of the blood coagulation system is adapted to perform a
      developmental function. Other mouse models show that the absence of platelets or
      of fibrinogen does not cause fetal wastage. Therefore, the role of thrombin in
      development may be independent of its effects on blood coagulation and instead
      may involve signal transduction on cells other than platelets.

PMID- 9636197
TI  - Human carbonic anhydrase XII: cDNA cloning, expression, and chromosomal
      localization of a carbonic anhydrase gene that is overexpressed in some renal
      cell cancers.
AB  - We report the cloning and characterization of a tumor-associated carbonic
      anhydrase (CA) that was identified in a human renal cell carcinoma (RCC) by
      serological expression screening with autologous antibodies. The cDNA sequence
      predicts a 354-amino acid polypeptide with a molecular mass of 39,448 Da that has
      features of a type I membrane protein. The predicted sequence includes a 29-amino
      acid signal sequence, a 261-amino acid CA domain, an additional short
      extracellular segment, a 26-amino acid hydrophobic transmembrane domain, and a
      hydrophilic C-terminal cytoplasmic tail of 29 amino acids that contains two
      potential phosphorylation sites. The extracellular CA domain shows 30-42%
      homology with known human CAs, contains all three Zn-binding histidine residues
      found in active CAs, and contains two potential sites for asparagine
      glycosylation. When expressed in COS cells, the cDNA produced a 43- to 44-kDa
      protein in membranes that had around one-sixth the CA activity of membranes from
      COS cells transfected with the same vector expressing bovine CA IV. We have
      designated this human protein CA XII. Northern blot analysis of normal tissues
      demonstrated a 4.5-kb transcript only in kidney and intestine. However, in 10% of
      patients with RCC, the CA XII transcript was expressed at much higher levels in
      the RCC than in surrounding normal kidney tissue. The CA XII gene was mapped by
      using fluorescence in situ hybridization to 15q22. CA XII is the second
      catalytically active membrane CA reported to be overexpressed in certain cancers.
      Its relationship to oncogenesis and its potential as a clinically useful tumor
      marker clearly merit further investigation.

PMID- 9636198
TI  - Expression of the peroxisome proliferator-activated receptor gamma (PPARgamma) in
      human atherosclerosis and regulation in macrophages by colony stimulating factors
      and oxidized low density lipoprotein.
AB  - The peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand
      dependent transcription factor that has been demonstrated to regulate fat cell
      development and glucose homeostasis. PPARgamma is also expressed in a subset of
      macrophages and negatively regulates the expression of several proinflammatory
      genes in response to natural and synthetic ligands. We here demonstrate that
      PPARgamma is expressed in macrophage foam cells of human atherosclerotic lesions,
      in a pattern that is highly correlated with that of oxidation-specific epitopes.
      Oxidized low density lipoprotein (oxLDL) and macrophage colony-stimulating
      factor, which are known to be present in atherosclerotic lesions, stimulated
      PPARgamma expression in primary macrophages and monocytic cell lines. PPARgamma
      mRNA expression was also induced in primary macrophages and THP-1 monocytic
      leukemia cells by the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA).
      Inhibition of protein kinase C blocked the induction of PPARgamma expression by
      TPA, but not by oxLDL, suggesting that more than one signaling pathway regulates
      PPARgamma expression in macrophages. TPA induced the expression of PPARgamma in
      RAW 264.7 macrophages by increasing transcription from the PPARgamma1 and
      PPARgamma3 promoters. In concert, these observations provide insights into the
      regulation of PPARgamma expression in activated macrophages and raise the
      possibility that PPARgamma ligands may influence the progression of
      atherosclerosis.

PMID- 9636199
TI  - Estimating sequestered parasite population dynamics in cerebral malaria.
AB  - Clinical investigation of malaria is hampered by the lack of a method for
      estimating the number of parasites that are sequestered in the tissues, for it is
      these parasites that are thought to be crucial to the pathogenesis of life
      threatening complications such as cerebral malaria. We present a method of
      estimating this hidden population by using clinical observations of peripheral
      parasitemia combined with an age-structured mathematical model of the parasite
      erythrocyte cycle. Applying the model to data from 217 Gambian children
      undergoing treatment for cerebral malaria we conclude that although artemether
      clears parasitemia more rapidly than quinine, the clearance of sequestered
      parasites is similar for the two drugs. The estimated sequestered mass was found
      to be a more direct predictor of fatal outcome than clinically observed
      parasitemia. This method allows a sequential analysis of sequestered parasite
      population dynamics in children suffering from cerebral malaria, and the results
      offer a possible explanation for why artemether provides less advantage than
      might have been expected over quinine in reducing mortality despite its rapid
      effect on circulating parasites.

PMID- 9636200
TI  - Cloning and characterization of human inducible nitric oxide synthase splice
      variants: a domain, encoded by exons 8 and 9, is critical for dimerization.
AB  - The inducible nitric oxide synthase (iNOS) contains an amino-terminal oxygenase
      domain, a carboxy-terminal reductase domain, and an intervening calmodulin
      binding region. For the synthesis of nitric oxide (NO), iNOS is active as a
      homodimer. The human iNOS mRNA is subject to alternative splicing, including
      deletion of exons 8 and 9 that encode amino acids 242-335 of the oxygenase
      domain. In this study, iNOS8(-)9(-) and full-length iNOS (iNOSFL) were cloned
      from bronchial epithelial cells. Expression of iNOS8(-)9(-) in 293 cell line
      resulted in generation of iNOS8(-)9(-) mRNA and protein but did not lead to NO
      production. In contrast to iNOSFL, iNOS8(-)9(-) did not form dimers. Similar to
      iNOSFL, iNOS8(-)9(-) exhibited NADPH-diaphorase activity and contained tightly
      bound calmodulin, indicating that the reductase and calmodulin-binding domains
      were functional. To identify sequences in exons 8 and 9 that are critical for
      dimerization, iNOSFL was used to construct 12 mutants, each with deletion of
      eight residues in the region encoded by exons 8 and 9. In addition, two "control"
      iNOS deletion mutants were synthesized, lacking either residues 45-52 of the
      oxygenase domain or residues 1131-1138 of the reductase domain. Whereas both
      control deletion mutants generated NO and formed dimers, none of the 12 other
      mutants formed dimers or generated NO. The region encoded by exons 8 and 9 is
      critical for iNOS dimer formation and NO production but not for reductase
      activity. This region could be a potential target for therapeutic interventions
      aimed at inhibiting iNOS dimerization and hence NO synthesis.

PMID- 9636201
TI  - Persistent inhibition of cell respiration by nitric oxide: crucial role of S
      nitrosylation of mitochondrial complex I and protective action of glutathione.
AB  - Both reversible and irreversible inhibition of mitochondrial respiration have
      been reported following the generation of nitric oxide (NO) by cells. Using J774
      cells, we have studied the effect of long-term exposure to NO on different
      enzymes of the respiratory chain. Our results show that, although NO inhibits
      complex IV in a way that is always reversible, prolonged exposure to NO results
      in a gradual and persistent inhibition of complex I that is concomitant with a
      reduction in the intracellular concentration of reduced glutathione. This
      inhibition appears to result from S-nitrosylation of critical thiols in the
      enzyme complex because it can be immediately reversed by exposing the cells to
      high intensity light or by replenishment of intracellular reduced glutathione.
      Furthermore, decreasing the concentration of reduced glutathione accelerates the
      process of persistent inhibition. Our results suggest that, although NO may
      regulate cell respiration physiologically by its action on complex IV, long-term
      exposure to NO leads to persistent inhibition of complex I and potentially to
      cell pathology.

PMID- 9636202
TI  - A unified theory of carcinogenesis based on order-disorder transitions in DNA
      structure as studied in the human ovary and breast.
AB  - Fourier transform-infrared/statistics models demonstrate that the malignant
      transformation of morphologically normal human ovarian and breast tissues
      involves the creation of a high degree of structural modification (disorder) in
      DNA, before restoration of order in distant metastases. Order-disorder
      transitions were revealed by methods including principal components analysis of
      infrared spectra in which DNA samples were represented by points in two
      dimensional space. Differences between the geometric sizes of clusters of points
      and between their locations revealed the magnitude of the order-disorder
      transitions. Infrared spectra provided evidence for the types of structural
      changes involved. Normal ovarian DNAs formed a tight cluster comparable to that
      of normal human blood leukocytes. The DNAs of ovarian primary carcinomas,
      including those that had given rise to metastases, had a high degree of disorder,
      whereas the DNAs of distant metastases from ovarian carcinomas were relatively
      ordered. However, the spectra of the metastases were more diverse than those of
      normal ovarian DNAs in regions assigned to base vibrations, implying increased
      genetic changes. DNAs of normal female breasts were substantially disordered
      (e.g., compared with the human blood leukocytes) as were those of the primary
      carcinomas, whether or not they had metastasized. The DNAs of distant breast
      cancer metastases were relatively ordered. These findings evoke a unified theory
      of carcinogenesis in which the creation of disorder in the DNA structure is an
      obligatory process followed by the selection of ordered, mutated DNA forms that
      ultimately give rise to metastases.

PMID- 9636203
TI  - Epitopes close to the apolipoprotein B low density lipoprotein receptor-binding
      site are modified by advanced glycation end products.
AB  - Advanced glycation end products (AGEs) are thought to contribute to the abnormal
      lipoprotein profiles and increased risk of cardiovascular disease of patients
      with diabetes and renal failure, in part by preventing apolipoprotein B (apoB)
      mediated cellular uptake of low density lipoproteins (LDL) by LDL receptors
      (LDLr). It has been proposed that AGE modification at one site in apoB, almost
      1,800 residues from the putative apoB LDLr-binding domain, may be sufficient to
      induce an apoB conformational change that prevents binding to the LDLr. To
      further explore this hypothesis, we used 29 anti-human apoB mAbs to identify
      other potential sites on apoB that may be modified by in vitro advanced glycation
      of LDL. Glycation of LDL caused a time-dependent decrease in its ability to bind
      to the LDLr and in the immunoreactivity of six distinct apoB epitopes, including
      two that flank the apoB LDLr-binding domain. ApoB appears to be modified at
      multiple sites by these criteria, as the loss of glycation-sensitive epitopes was
      detected on both native glycated LDL and denatured, delipidated glycated apoB.
      Moreover, residues directly within the putative apoB LDLr-binding site are not
      apparently modified in glycated LDL. We propose that the inability of LDL
      modified by AGEs to bind to the LDLr is caused by modification of residues
      adjacent to the putative LDLr-binding site that were undetected by previous
      immunochemical studies. AGE modification either eliminates the direct
      participation of the residues in LDLr binding or indirectly alters the
      conformation of the apoB LDLr-binding site.

PMID- 9636204
TI  - Boosting with recombinant vaccinia increases immunogenicity and protective
      efficacy of malaria DNA vaccine.
AB  - To enhance the efficacy of DNA malaria vaccines, we evaluated the effect on
      protection of immunizing with various combinations of DNA, recombinant vaccinia
      virus, and a synthetic peptide. Immunization of BALB/c mice with a plasmid
      expressing Plasmodium yoelii (Py) circumsporozoite protein (CSP) induces H-2Kd
      restricted CD8+ cytotoxic T lymphocyte (CTL) responses and CD8+ T cell- and
      interferon (IFN)-gamma-dependent protection of mice against challenge with Py
      sporozoites. Immunization with a multiple antigenic peptide, including the only
      reported H-2Kd-restricted CD8+ T cell epitope on the PyCSP (PyCSP CTL multiple
      antigenic peptide) and immunization with recombinant vaccinia expressing the
      PyCSP induced CTL but only modest to minimal protection. Mice were immunized with
      PyCSP DNA, PyCSP CTL multiple antigenic peptide, or recombinant vaccinia
      expressing PyCSP, were boosted 9 wk later with the same immunogen or one of the
      others, and were challenged. Only mice immunized with DNA and boosted with
      vaccinia PyCSP (D-V) (11/16: 69%) or DNA (D-D) (7/16: 44%) had greater protection
      (P < 0. 0007) than controls. D-V mice had significantly higher individual levels
      of antibodies and class I-restricted CTL activity than did D-D mice; IFN-gamma
      production by ELIspot also was higher in D-V than in D-D mice. In a second
      experiment, three different groups of D-V mice each had higher levels of
      protection than did D-D mice, and IFN-gamma production was significantly greater
      in D-V than in D-D mice. The observation that priming with PyCSP DNA and boosting
      with vaccinia-PyCSP is more immunogenic and protective than immunizing with PyCSP
      DNA alone supports consideration of a similar sequential immunization approach in
      humans.

PMID- 9636205
TI  - Late-onset minor and major depression: early evidence for common neuroanatomical
      substrates detected by using MRI.
AB  - The purpose of our study was to examine the neuroanatomical correlates of late
      onset minor and major depression and to compare them with similar measures
      obtained from nondepressed controls. Our study groups were comprised of 18
      patients with late-onset minor depression, 35 patients diagnosed with late-onset
      major depression, and 30 nondepressed controls. All subjects were scanned by
      using a 1. 5-tesla MRI scanner. Absolute whole brain volume and normalized
      measures of prefrontal and temporal lobe volumes were obtained and used for
      comparison among groups. Our findings indicate that patients with minor
      depression present with specific neuroanatomical abnormalities that are
      comparable with the major depression group but significantly different from the
      controls. Normalized prefrontal lobe volumes show a significant linear trend with
      severity of depression, with volumes decreasing with illness severity. Whole
      brain volumes did not differ significantly among groups. These findings have
      broad implications for the biology of late-life depression and suggest that there
      may be common neurobiological substrates that underlie all clinically significant
      forms of late-onset mood disturbances.

PMID- 9636206
TI  - Inactivation of tyrosine hydroxylase by nitration following exposure to
      peroxynitrite and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
AB  - The decrement in dopamine levels exceeds the loss of dopaminergic neurons in
      Parkinson's disease (PD) patients and experimental models of PD. This discrepancy
      is poorly understood and may represent an important event in the pathogenesis of
      PD. Herein, we report that the rate-limiting enzyme in dopamine synthesis,
      tyrosine hydroxylase (TH), is a selective target for nitration following exposure
      of PC12 cells to either peroxynitrite or 1-methyl-4-phenylpyridiniun ion (MPP+).
      Nitration of TH also occurs in mouse striatum after MPTP administration.
      Nitration of tyrosine residues in TH results in loss of enzymatic activity. In
      the mouse striatum, tyrosine nitration-mediated loss in TH activity parallels the
      decline in dopamine levels whereas the levels of TH protein remain unchanged for
      the first 6 hr post MPTP injection. Striatal TH was not nitrated in mice
      overexpressing copper/zinc superoxide dismutase after MPTP administration,
      supporting a critical role for superoxide in TH tyrosine nitration. These results
      indicate that tyrosine nitration-induced TH inactivation and consequently
      dopamine synthesis failure, represents an early and thus far unidentified
      biochemical event in MPTP neurotoxic process. The resemblance of the MPTP model
      with PD suggests that a similar phenomenon may occur in PD, influencing the
      severity of parkisonian symptoms.

PMID- 9636207
TI  - KARP-1 is induced by DNA damage in a p53- and ataxia telangiectasia mutated
      dependent fashion.
AB  - The KARP-1 (Ku86 Autoantigen Related Protein-1) gene, which is expressed from the
      human Ku86 autoantigen locus, appears to play a role in mammalian DNA double
      strand break repair as a regulator of the DNA-dependent protein kinase complex.
      Here we demonstrate that KARP-1 gene expression is significantly up-regulated
      following exposure of cells to DNA damage. KARP-1 mRNA induction was completely
      dependent on the ataxia telangiectasia and p53 gene products, consistent with the
      presence of a p53 binding site within the second intron of the KARP-1 locus.
      These observations link ataxia telangiectasia, p53, and KARP-1 in a common
      pathway.

PMID- 9636208
TI  - Molecular analysis of CaMnt1p, a mannosyl transferase important for adhesion and
      virulence of Candida albicans.
AB  - There is an immediate need for identification of new antifungal targets in
      opportunistic pathogenic fungi like Candida albicans. In the past, efforts have
      focused on synthesis of chitin and glucan, which confer mechanical strength and
      rigidity upon the cell wall. This paper describes the molecular analysis of
      CaMNT1, a gene involved in synthesis of mannoproteins, the third major class of
      macromolecule found in the cell wall. CaMNT1 encodes an alpha-1, 2-mannosyl
      transferase, which adds the second mannose residue in a tri-mannose
      oligosaccharide structure which represents O-linked mannan in C. albicans. The
      deduced amino acid sequence suggests that CaMnt1p is a type II membrane protein
      residing in a medial Golgi compartment. The absence of CaMnt1p reduced the
      ability of C. albicans cells to adhere to each other, to human buccal epithelial
      cells, and to rat vaginal epithelial cells. Both heterozygous and homozygous
      Camnt1 null mutants of C. albicans showed strong attenuation of virulence in
      guinea pig and mouse models of systemic candidosis, which, in guinea pigs, could
      be attributed to a decreased ability to reach and/or adhere internal organs.
      Therefore, correct CaMnt1p-mediated O-linked mannosylation of proteins is
      critical for adhesion and virulence of C. albicans.

PMID- 9636209
TI  - The crucial role of polymorphonuclear leukocytes in resistance to Salmonella
      dublin infections in genetically susceptible and resistant mice.
AB  - Macrophages are considered to be the mediators of resistance to extra-intestinal
      Salmonella infections. Nevertheless, the initial cellular response to Salmonella
      infections consists primarily of polymorphonuclear leukocytes (PMN). To determine
      whether PMN serve an important function for the infected host, we made mice
      neutropenic with the rat mAb to RB6-8C5 and infected them i.v. with approximately
      10(3) Salmonella dublin or an isogenic derivative that lacks the virulence
      plasmid (LD842). We infected BALB/c mice, which have a point mutation in the
      macrophage-expressed gene Nramp1 that makes them susceptible to Salmonella, and
      BALB/c.D2 congenic mice, which have the wild-type Nramp1 gene that makes them
      resistant to Salmonella. Both mouse strains were resistant to LD842, and
      neutropenia made only the BALB/c strain susceptible to this infection.
      Neutropenic congenic mice, however, were susceptible only to wild-type S. dublin
      (plasmid+). These results show a complex interplay between plasmid-virulence
      genes in Salmonella, host macrophages, and PMN. Mice with normal macrophages need
      PMN to defend against nontyphoid Salmonella that carry a virulence plasmid but
      not against Salmonella without virulence plasmids. Mice with a mutant Nramp1 gene
      need PMN to defend against all Salmonella, even those that lack virulence
      plasmids. These results, plus the evidence that PMN kill Salmonella efficiently
      in vitro, suggest that Salmonella have adapted to grow inside macrophages where
      they are relatively sheltered from PMN. The adaptations that allow Salmonella to
      survive in macrophages do not protect them from PMN.

PMID- 9636210
TI  - The ability of HIV type 1 to use CCR-3 as a coreceptor is controlled by envelope
      V1/V2 sequences acting in conjunction with a CCR-5 tropic V3 loop.
AB  - Although infection by primary HIV type 1 (HIV-1) isolates normally requires the
      functional interaction of the viral envelope protein with both CD4 and the CCR-5
      coreceptor, a subset of such isolates also are able to use the distinct CCR-3
      receptor. By analyzing the ability of a series of wild-type and chimeric HIV-1
      envelope proteins to mediate CCR-3-dependent infection, we have determined that
      CCR-3 tropism maps to the V1 and V2 variable region of envelope. Although
      substitution of the V1/V2 region of a CCR-3 tropic envelope into the context of a
      CCR-5 tropic envelope is both necessary and sufficient to confer CCR-3 tropism,
      this same substitution has no phenotypic effect when inserted into a CXCR-4
      tropic HIV-1 envelope context. However, this latter chimera acquires both CCR-3
      and CCR-5 tropism when a CCR-5 tropic V3 loop sequence also is introduced. These
      data demonstrate that the V1/2 region of envelope can, like the V3 loop region,
      encode a particular coreceptor requirement and suggest that a functional
      envelope:CCR-3 interaction may depend on the cooperative interaction of CCR-3
      with both the V1/V2 and the V3 region of envelope.

PMID- 9636211
TI  - A negative regulator mediates quorum-sensing control of exopolysaccharide
      production in Pantoea stewartii subsp. stewartii.
AB  - Classical quorum-sensing (autoinduction) regulation, as exemplified by the lux
      system of Vibrio fischeri, requires N-acyl homoserine lactone (AHL) signals to
      stimulate cognate transcriptional activators for the cell density-dependent
      expression of specific target gene systems. For Pantoea stewartii subsp.
      stewartii, a bacterial pathogen of sweet corn and maize, the extracellular
      polysaccharide (EPS) stewartan is a major virulence factor, and its production is
      controlled by quorum sensing in a population density-dependent manner. Two genes,
      esaI and esaR, encode essential regulatory proteins for quorum sensing. EsaI is
      the AHL signal synthase, and EsaR is the cognate gene regulator. esaI, DeltaesaR,
      and DeltaesaI-esaR mutations were constructed to establish the regulatory role of
      EsaR. We report here that strains containing an esaR mutation produce high levels
      of EPS independently of cell density and in the absence of the AHL signal. Our
      data indicate that quorum-sensing regulation in P. s. subsp. stewartii, in
      contrast to most other described systems, uses EsaR to repress EPS synthesis at
      low cell density, and that derepression requires micromolar amounts of AHL. In
      addition, derepressed esaR strains, which synthesize EPS constitutively at low
      cell densities, were significantly less virulent than the wild-type parent. This
      finding suggests that quorum sensing in P. s. subsp. stewartii may be a mechanism
      to delay the expression of EPS during the early stages of infection so that it
      does not interfere with other mechanisms of pathogenesis.

PMID- 9636213
TI  - Cocaine reward models: conditioned place preference can be established in
      dopamine- and in serotonin-transporter knockout mice.
AB  - Cocaine and methylphenidate block uptake by neuronal plasma membrane transporters
      for dopamine, serotonin, and norepinephrine. Cocaine also blocks voltage-gated
      sodium channels, a property not shared by methylphenidate. Several lines of
      evidence have suggested that cocaine blockade of the dopamine transporter (DAT),
      perhaps with additional contributions from serotonin transporter (5-HTT)
      recognition, was key to its rewarding actions. We now report that knockout mice
      without DAT and mice without 5-HTT establish cocaine-conditioned place
      preferences. Each strain displays cocaine-conditioned place preference in this
      major mouse model for assessing drug reward, while methylphenidate-conditioned
      place preference is also maintained in DAT knockout mice. These results have
      substantial implications for understanding cocaine actions and for strategies to
      produce anticocaine medications.

PMID- 9636212
TI  - Cyclic AMP regulates potassium channel expression in C6 glioma by destabilizing
      Kv1.1 mRNA.
AB  - The tissue distributions and physiological properties of a variety of cloned
      voltage-gated potassium channel genes have been characterized extensively, yet
      relatively little is known about the mechanisms controlling expression of these
      genes. Here, we report studies on the regulation of Kv1.1 expressed endogenously
      in the C6 glioma cell line. We demonstrate that elevation of intracellular cAMP
      leads to the accelerated degradation of Kv1.1 RNA. The cAMP-induced decrease in
      Kv1.1 RNA is followed by a decrease in Kv1. 1 protein and a decrease in the whole
      cell sustained K+ current amplitude. Dendrotoxin-I, a relatively specific blocker
      of Kv1.1, blocks 96% of the sustained K+ current in glioma cells, causing a shift
      in the resting membrane potential from -40 mV to -7 mV. These data suggest that
      expression of Kv1.1 contributes to setting the resting membrane potential in
      undifferentiated glioma cells. We therefore suggest that receptor-mediated
      elevation of cAMP reduces outward K+ current density by acting at the
      translational level to destabilize Kv1.1 RNA, an additional mechanism for
      regulating potassium channel gene expression.

PMID- 9636215
TI  - Low dimensionality of supraspinally induced force fields.
AB  - Recent experiments using electrical and N-methyl-D-aspartate microstimulation of
      the spinal cord gray matter and cutaneous stimulation of the hindlimb of
      spinalized frogs have provided evidence for a modular organization of the frog's
      spinal cord circuitry. A "module" is a functional unit in the spinal cord
      circuitry that generates a specific motor output by imposing a specific pattern
      of muscle activation. The output of a module can be characterized as a force
      field: the collection of the isometric forces generated at the ankle over
      different locations in the leg's workspace. Different modules can be combined
      independently so that their force fields linearly sum. The goal of this study was
      to ascertain whether the force fields generated by the activation of supraspinal
      structures could result from combinations of a small number of modules. We
      recorded a set of force fields generated by the electrical stimulation of the
      vestibular nerve in seven frogs, and we performed a principal component analysis
      to study the dimensionality of this set. We found that 94% of the total variation
      of the data is explained by the first five principal components, a result that
      indicates that the dimensionality of the set of fields evoked by vestibular
      stimulation is low. This result is compatible with the hypothesis that vestibular
      fields are generated by combinations of a small number of spinal modules.

PMID- 9636214
TI  - Dynamic characteristics and adaptability of mouse vestibulo-ocular and
      optokinetic response eye movements and the role of the flocculo-olivary system
      revealed by chemical lesions.
AB  - The dynamic characteristics of reflex eye movements were measured in two strains
      of chronically prepared mice by using an infrared television camera system. The
      horizontal vestibulo-ocular reflex (HVOR) and horizontal optokinetic response
      (HOKR) were induced by sinusoidal oscillations of a turntable, in darkness, by 10
      degrees (peak to peak) at 0.11-0.50 Hz and of a checked-pattern screen, in light,
      by 5-20 degreesat 0.11-0.17 Hz, respectively. The gains and phases of the HVOR
      and HOKR of the C57BL/6 mice were nearly equivalent to those of rabbits and rats,
      whereas the 129/Sv mice exhibited very low gains in the HVOR and moderate phase
      lags in the HOKR, suggesting an inherent sensory-motor anomaly. Adaptability of
      the HOKR was examined in C57BL/6 mice by sustained screen oscillation. When the
      screen was oscillated by 10 degrees at 0.17 Hz, which induced sufficient retinal
      slips, the gain of the HOKR increased by 0.08 in 1 h on average, whereas the
      stimuli that induced relatively small or no retinal slips affected the gain very
      little. Lesions of the flocculi induced by local applications of 0. 1% ibotenic
      acid and lesions of the inferior olivary nuclei induced by i.p. injection of 3
      acetylpyridine in C57BL/6 mice little affected the dynamic characteristics of the
      HVOR and HOKR, but abolished the adaptation of the HOKR. These results indicate
      that the olivo-floccular system plays an essential role in the adaptive control
      of the ocular reflex in mice, as suggested in other animal species. The data
      presented provide the basis for analyzing the reflex eye movements of genetically
      engineered mice.

PMID- 9636216
TI  - Dynamic mapping at the laminar level of odor-elicited responses in rat olfactory
      bulb by functional MRI.
AB  - We have applied functional MRI (fMRI) based on blood oxygenation level-dependent
      (BOLD) image-contrast to map odor-elicited olfactory responses at the laminar
      level in the rat olfactory bulb (OB) elicited by iso-amyl acetate (10(-2)
      dilution of saturated vapor) with spatial and temporal resolutions of
      220x220x1,000 micro(m) and 36 s. The laminar structure of the OB was clearly
      depicted by high-resolution in vivo anatomical MRI with spatial resolution of
      110x110x1,000 micro(m). In repeated BOLD fMRI measurements, highly significant (P
      < 0.001) foci were located in the outer layers of both OBs. The occurrence of
      focal OB activity within a domain at the level of individual glomeruli or groups
      of glomeruli was corroborated on an intra- and inter-animal basis under
      anesthetized conditions with this noninvasive method. The dynamic studies
      demonstrated that the odor-elicited BOLD activations were highly reproducible on
      a time scale of minutes, whereas over tens of minutes the activations sometimes
      varied slowly. We found large BOLD signal (DeltaS/S = 10-30%) arising from the
      olfactory nerve layer, which is devoid of synapses and composed of unmyelinated
      fibers and glial cells. Our results support previous studies with other methods
      showing that odors elicit activity within glomerular layer domains in the
      mammalian OB, and extend the analysis to shorter time periods at the level of
      individual glomeruli or groups of glomeruli. With further improvement, BOLD fMRI
      should be ideal for systematic analysis of the functional significance of
      individual glomeruli in olfactory information encoding and of spatiotemporal
      processing within the olfactory system.

PMID- 9636217
TI  - Functional organization of spatial and nonspatial working memory processing
      within the human lateral frontal cortex.
AB  - The present study used functional magnetic resonance imaging to demonstrate that
      performance of visual spatial and visual nonspatial working memory tasks involve
      the same regions of the lateral prefrontal cortex when all factors unrelated to
      the type of stimulus material are appropriately controlled. These results provide
      evidence that spatial and nonspatial working memory may not be mediated,
      respectively, by mid-dorsolateral and mid-ventrolateral regions of the frontal
      lobe, as widely assumed, and support the alternative notion that specific regions
      of the lateral prefrontal cortex make identical executive functional
      contributions to both spatial and nonspatial working memory.

PMID- 9636218
TI  - Nerve growth factor inhibits sympathetic neurons' response to an injury cytokine.
AB  - Axonal damage to adult peripheral neurons causes changes in neuronal gene
      expression. For example, axotomized sympathetic, sensory, and motor neurons begin
      to express galanin mRNA and protein, and recent evidence suggests that galanin
      plays a role in peripheral nerve regeneration. Previous studies in sympathetic
      and sensory neurons have established that galanin expression is triggered by two
      consequences of nerve transection: the induction of leukemia inhibitory factor
      (LIF) and the reduction in the availability of the target-derived factor, nerve
      growth factor. It is shown in the present study that no stimulation of galanin
      expression occurs following direct application of LIF to intact neurons in the
      superior cervical sympathetic ganglion. Injection of animals with an antiserum to
      nerve growth factor concomitant with the application of LIF, on the other hand,
      does stimulate galanin expression. The data suggest that the response of neurons
      to an injury factor, LIF, is affected by whether the neurons still receive
      trophic signals from their targets.

PMID- 9636219
TI  - Prominence of the dopamine D2 short isoform in dopaminergic pathways.
AB  - As a result of alternative splicing, the D2 gene of the dopamine receptor family
      exists in two isoforms. The D2 long is characterized by the insertion of 29 amino
      acids in the third cytoplasmic loop, which is absent in the short isoform. We
      have produced subtype-specific antibodies against both the D2 short and D2 long
      isoforms and found a unique compartmentalization between these two isoforms in
      the primate brain. The D2 short predominates in the cell bodies and projection
      axons of the dopaminergic cell groups of the mesencephalon and hypothalamus,
      whereas the D2 long is more strongly expressed by neurons in the striatum and
      nucleus accumbens, structures targeted by dopaminergic fibers. These results show
      that the splice variants of the dopamine D2 receptor are differentially
      distributed and possess distinct functions. The strategic localization of the D2
      short isoform in dopaminergic cell bodies and axons strongly suggests that this
      isoform is the likely dopamine autoreceptor, whereas the D2 long isoform is
      primarily a postsynaptic receptor.

PMID- 9636220
TI  - Mutation in the tau gene in familial multiple system tauopathy with presenile
      dementia.
AB  - Familial multiple system tauopathy with presenile dementia (MSTD) is a
      neurodegenerative disease with an abundant filamentous tau protein pathology. It
      belongs to the group of familial frontotemporal dementias with Parkinsonism
      linked to chromosome 17 (FTDP-17), a major class of inherited dementing disorders
      whose genetic basis is unknown. We now report a G to A transition in the intron
      following exon 10 of the gene for microtubule-associated protein tau in familial
      MSTD. The mutation is located at the 3' neighboring nucleotide of the GT splice
      donor site and disrupts a predicted stem-loop structure. We also report an
      abnormal preponderance of soluble tau protein isoforms with four microtubule
      binding repeats over isoforms with three repeats in familial MSTD. This most
      likely accounts for our previous finding that sarkosyl-insoluble tau protein
      extracted from the filamentous deposits in familial MSTD consists only of tau
      isoforms with four repeats. These findings reveal that a departure from the
      normal ratio of four-repeat to three-repeat tau isoforms leads to the formation
      of abnormal tau filaments. The results show that dysregulation of tau protein
      production can cause neurodegeneration and imply that the FTDP-17 gene is the tau
      gene. This work has major implications for Alzheimer's disease and other
      tauopathies.

PMID- 9636221
TI  - Dopamine-dependent responses to morphine depend on glucocorticoid receptors.
AB  - Previous work has shown that glucocorticoid hormones facilitate the behavioral
      and dopaminergic effects of morphine. In this study we examined the possible role
      in these effects of the two central corticosteroid receptor types:
      mineralocorticoid receptor (MR), and glucocorticoid receptor (GR). To accomplish
      this, specific antagonists of these receptors were infused
      intracerebroventricularly and 2 hr later we measured: (i) locomotor activity
      induced by a systemic injection of morphine (2 mg/kg); (ii) locomotor activity
      induced by an infusion of morphine (1 microg per side) into the ventral tegmental
      area, which is a dopamine-dependent behavioral response to morphine; (iii)
      morphine-induced dopamine release in the nucleus accumbens, a dopaminergic
      projection site mediating the locomotor and reinforcing effects of drugs of
      abuse. Blockade of MRs by spironolactone had no significant effects on locomotion
      induced by systemic morphine. In contrast, blockade of GRs by either RU38486 or
      RU39305, which is devoid of antiprogesterone effects, reduced the locomotor
      response to morphine, and this effect was dose dependent. GR antagonists also
      reduced the locomotor response to intraventral tegmental area morphine as well as
      the basal and morphine-induced increase in accumbens dopamine, as measured by
      microdialysis in freely moving rats. In contrast, spironolactone did not modify
      dopamine release. In conclusion, glucocorticoids, via GRs, facilitate the
      dopamine-dependent behavioral effects of morphine, probably by facilitating
      dopamine release. The possibility of decreasing the behavioral and dopaminergic
      effects of opioids by an acute administration of GR antagonists may open new
      therapeutic strategies for treatment of drug addiction.

PMID- 9636222
TI  - Phosphatidylcholine-specific phospholipase C regulates glutamate-induced nerve
      cell death.
AB  - Phosphatidylcholine-specific phospholipase C (PC-PLC) is a necessary intermediate
      in transducing apoptotic signals for tumor necrosis factor and Fas/Apo-1 ligands
      in nonneuronal cells. The data presented here show that PC-PLC also is required
      in oxidative glutamate-induced programmed cell death of both immature cortical
      neurons and a hippocampal nerve cell line, HT22. In oxidative glutamate toxicity,
      which is distinct from excitotoxicity, glutamate interferes with cystine uptake
      by blocking the cystine/glutamate antiporter, indirectly causing a depletion of
      intracellular glutathione. A PC-PLC inhibitor blocks oxidative glutamate
      toxicity, and exogenous PC-PLC potentiates glutamate toxicity. The inhibition of
      PC-PLC uncouples the cystine uptake from glutamate inhibition, allowing the
      maintenance of glutathione synthesis and cell viability. These data suggest that
      PC-PLC modulates neuronal cell death through a mechanism that is distinct from
      that involved in nonneuronal apoptosis.

PMID- 9636223
TI  - Activation of ventrolateral preoptic neurons by the somnogen prostaglandin D2.
AB  - Prostaglandin D2 (PGD2) is an extensively studied sleep-promoting substance, but
      the neuroanatomical basis of PGD2-induced sleep is only partially understood. To
      determine potential regions involved in this response, we used Fos
      immunohistochemistry to identify neurons activated by infusion of PGD2 into the
      subarachnoid space below the rostral basal forebrain. PGD2 increased nonrapid eye
      movement sleep and induced striking expression of Fos in the ventrolateral
      preoptic area (VLPO), a cluster of neurons that may promote sleep by inhibiting
      the tuberomammillary nucleus, the source of the ascending histaminergic arousal
      system. Fos expression in the VLPO was positively correlated with the preceding
      amount of sleep and negatively correlated with Fos expression in the
      tuberomammillary nucleus. PGD2 also increased Fos immunoreactivity in the basal
      leptomeninges and several regions implicated in autonomic regulation. These
      observations suggest that PGD2 may induce sleep via leptomeningeal PGD2 receptors
      with subsequent activation of the VLPO.

PMID- 9636224
TI  - Antisense oligonucleotides against alpha1E reduce R-type calcium currents in
      cerebellar granule cells.
AB  - Many neurons of the central nervous system display multiple high voltage
      activated Ca2+ currents, pharmacologically classified as L-, N-, P-, Q-, and R
      type. Of these current types, the R-type is the least understood. The leading
      candidate for the molecular correlate of R-type currents in cerebellar granule
      cells is the alpha1E subunit, which yields Ca2+ currents very similar to the R
      type when expressed in heterologous systems. As a complementary approach, we
      tested whether antisense oligonucleotides against alpha1E could decrease the
      expression of R-type current in rat cerebellar granule neurons in culture. Cells
      were supplemented with either antisense or sense oligonucleotides and whole-cell
      patch clamp recordings were obtained after 6-8 days in vitro. Incubation with
      alpha1E antisense oligonucleotide caused a 52.5% decrease in the peak R-type
      current density, from -10 +/- 0.6 picoamperes/picofarad (pA/pF) (n = 6) in the
      untreated controls to -4.8 +/- 0.8 pA/pF (n = 11) (P < 0.01). In contrast, no
      significant changes in the current expression were seen in sense oligonucleotide
      treated cells (-11.3 +/- 3.2 pA/pF). The specificity of the alpha1E antisense
      oligonucleotides was supported by the lack of change in estimates of the P/Q
      current amplitude. Furthermore, antisense and sense oligonucleotides against
      alpha1A did not affect R-type current expression (-11.5 +/- 1.7 and -11.7 +/- 1.7
      pA/pF, respectively), whereas the alpha1A antisense oligonucleotide significantly
      reduced whole cell currents under conditions in which P/Q current is dominant.
      Our results support the hypothesis that members of the E class of alpha1 subunits
      support the high voltage-activated R-type current in cerebellar granule cells.

PMID- 9636225
TI  - Proteinase-activated receptor 2 (PAR2)-activating peptides: identification of a
      receptor distinct from PAR2 that regulates intestinal transport.
AB  - The effects of PAR2-activating PAR2-activating peptides, SLIGRL (SL)-NH2, and
      trans-cinnamoyl-LIGRLO (tc)-NH2 were compared with the action of trypsin,
      thrombin, and the PAR1 selective-activating peptide: Ala-parafluoroPhe-Arg
      cyclohexylAla-Citrulline-Tyr (Cit)-NH2 for stimulating intestinal ion transport.
      These agonists were added to the serosa of stripped rat jejunum segments mounted
      in Ussing chambers, and short circuit current (Isc) was used to monitor active
      ion transport. The relative potencies of these agonists also were evaluated in
      two bioassays specific for the activation of rat PAR2: a cloned rat PAR2 cell
      calcium-signaling assay (PAR2-KNRK cells) and an aorta ring relaxation (AR)
      assay. In the Isc assay, all agonists, except thrombin, induced an Isc increase.
      The SL-NH2-induced Isc changes were blocked by indomethacin but not by
      tetrodotoxin. The relative potencies of the agonists in the Isc assay
      (trypsin>>SL-NH2>tc-NH2>Cit-NH2) were strikingly different from their relative
      potencies in the cloned PAR2-KNRK cell calcium assay (trypsin>>>tc-NH2 congruent
      with SL-NH2>>>Cit-NH2) and in the AR assay (trypsin>>>tc-NH2 congruent with SL
      NH2). Furthermore, all agonists were maximally active in the PAR2-KNRK cell and
      AR assays at concentrations that were one (PAR2 -activating peptides) or two
      (trypsin) orders of magnitude lower than those required to activate intestinal
      transport. Based on the distinct potency profile for these agonists and the
      considerable differences in the concentration ranges required to induce an Isc
      effect in the intestinal assay compared with the PAR2-KNRK and AR assays, we
      conclude that a proteinase-activated receptor, pharmacologically distinct from
      PAR2 and PAR1, is present in rat jejunum and regulates intestinal transport via a
      prostanoid-mediated mechanism.

PMID- 9636226
TI  - Evidence of insulin-stimulated phosphorylation and activation of the mammalian
      target of rapamycin mediated by a protein kinase B signaling pathway.
AB  - The effects of insulin on the mammalian target of rapamycin, mTOR, were
      investigated in 3T3-L1 adipocytes. mTOR protein kinase activity was measured in
      immune complex assays with recombinant PHAS-I as substrate. Insulin-stimulated
      kinase activity was clearly observed when immunoprecipitations were conducted
      with the mTOR antibody, mTAb2. Insulin also increased by severalfold the 32P
      content of mTOR that was determined after purifying the protein from 32P-labeled
      adipocytes with rapamycin.FKBP12 agarose beads. Insulin affected neither the
      amount of mTOR immunoprecipitated nor the amount of mTOR detected by
      immunoblotting with mTAb2. However, the hormone markedly decreased the reactivity
      of mTOR with mTAb1, an antibody that activates the mTOR protein kinase. The
      effects of insulin on increasing mTOR protein kinase activity and on decreasing
      mTAb1 reactivity were abolished by incubating mTOR with protein phosphatase 1.
      Interestingly, the epitope for mTAb1 is located near the COOH terminus of mTOR in
      a 20-amino acid region that includes consensus sites for phosphorylation by
      protein kinase B (PKB). Experiments were performed in MER-Akt cells to
      investigate the role of PKB in controlling mTOR. These cells express a PKB-mutant
      estrogen receptor fusion protein that is activated when the cells are exposed to
      4-hydroxytamoxifen. Activating PKB with 4-hydroxytamoxifen mimicked insulin by
      decreasing mTOR reactivity with mTAb1 and by increasing the PHAS-I kinase
      activity of mTOR. Our findings support the conclusion that insulin activates mTOR
      by promoting phosphorylation of the protein via a signaling pathway that contains
      PKB.

PMID- 9636227
TI  - A neuromodulatory role of interleukin-1beta in the hippocampus.
AB  - It is widely accepted that interleukin-1beta (IL-1beta), a cytokine produced not
      only by immune cells but also by glial cells and certain neurons influences brain
      functions during infectious and inflammatory processes. It is still unclear,
      however, whether IL-1 production is triggered under nonpathological conditions
      during activation of a discrete neuronal population and whether this production
      has functional implications. Here, we show in vivo and in vitro that IL-1beta
      gene expression is substantially increased during long-term potentiation of
      synaptic transmission, a process considered to underlie certain forms of learning
      and memory. The increase in gene expression was long lasting, specific to
      potentiation, and could be prevented by blockade of potentiation with the N
      methyl-D-aspartate (NMDA) receptor antagonist, (+/-)-2-amino-5-phosphonopentanoic
      acid (AP-5). Furthermore, blockade of IL-1 receptors by the specific interleukin
      1 receptor antagonist (IL-1ra) resulted in a reversible impairment of long-term
      potentiation maintenance without affecting its induction. These results show for
      the first time that the production of biologically significant amounts of IL
      1beta in the brain can be induced by a sustained increase in the activity of a
      discrete population of neurons and suggest a physiological involvement of this
      cytokine in synaptic plasticity.

PMID- 9636228
TI  - Pancreatic beta cells synthesize and secrete nerve growth factor.
AB  - Differentiation and function of pancreatic beta cells are regulated by a variety
      of hormones and growth factors, including nerve growth factor (NGF). Whether this
      is an endocrine or autocrine/paracrine role for NGF is not known. We demonstrate
      that NGF is produced and secreted by adult rat pancreatic beta cells. NGF
      secretion is increased in response to elevated glucose or potassium, but
      decreased in response to dibutyryl cAMP. Moreover, steady-state levels of NGF
      mRNA are down-regulated by dibutyryl cAMP, which is opposite to the effect of
      cAMP on insulin release. NGF-stimulated changes in morphology and function are
      mediated by high-affinity Trk A receptors in other mammalian cells. Trk A
      receptors are present in beta cells and steady-state levels of Trk A mRNA are
      modulated by NGF and dibutyryl cAMP. Taken together, these findings suggest
      endocrine and autocrine roles for pancreatic beta-cell NGF, which, in turn, could
      be related to the pathogenesis of diabetes mellitus where serum NGF levels are
      diminished.

PMID- 9636229
TI  - Conformational changes couple Na+ and glucose transport.
AB  - The mechanism by which cotransport proteins couple their substrates across cell
      membranes is not known. A commonly proposed model is that cotransport results
      from ligand-induced conformational transitions that change the accessibility of
      ligand-binding sites from one side of the membrane to the other. To test this
      model, we have measured the accessibility of covalent probes to a cysteine
      residue (Q457C) placed in the putative sugar-translocation domain of the
      Na+/glucose cotransporter (SGLT1). The mutant protein Q457C was able to transport
      sugar, but transport was abolished after alkylation by methanethiosulfonate
      reagents. Alkylation blocked sugar translocation but not sugar binding.
      Accessibility of Q457C to alkylating reagents required external Na+ and was
      blocked by external sugar and phlorizin. The voltage dependence of accessibility
      was directly correlated with the presteady-state charge movement of SGLT1.
      Voltage-jump experiments with rhodamine-6-maleimide-labeled Q457C showed that the
      time course and level of changes in fluorescence closely followed the presteady
      state charge movement. We conclude that conformational changes are responsible
      for the coupling of Na+ and sugar transport and that Q457 plays a critical role
      in sugar translocation by SGLT1.

PMID- 9636230
TI  - Adenosine acts by A1 receptors to stimulate release of prolactin from anterior
      pituitaries in vitro.
AB  - Adenosine has been identified in the anterior pituitary gland and is secreted
      from cultured folliculostellate (FS) cells. To determine whether adenosine
      controls the secretion of anterior pituitary hormones in vitro, adenosine was
      incubated with anterior pituitaries. It stimulated prolactin (PRL) release at the
      lowest concentration used (10(-10) M); the stimulation peaked at 10(-8) M with a
      threefold increase in release and declined to minimal stimulation at 10(-4) and
      10(-3) M. Follicle-stimulating hormone release was maximally inhibited at 10(-8)
      M, whereas luteinizing hormone release was not significantly inhibited. Two
      selective A1 adenosine receptor antagonists (10(-7) or 10(-5) M) had no effect on
      basal PRL release, but either antagonist completely blocked the response to the
      most effective concentration of adenosine (10(-8) M). In contrast, a highly
      specific A2 receptor antagonist (10(-7) or 10(-5) M) had no effect on basal PRL
      release or the stimulation of PRL release induced by adenosine (10(-8) M). We
      conclude that adenosine acts to stimulate PRL release in vitro by activating A1
      receptors. Since the A1 receptors decrease intracellular-free calcium, this would
      decrease the activation of nitric oxide synthase in the FS cells, resulting in
      decreased release of nitric oxide (NO). NO inhibits PRL release by activating
      guanylate cyclase that synthesizes cGMP from GTP; cGMP concentrations increase in
      the lactotrophs leading to inhibition of PRL release. In the case of adenosine,
      NO release from the FS cells decreases, resulting in decreased concentrations of
      NO in the lactotrophs, consequent decreased cGMP formation, and resultant
      increased PRL release.

PMID- 9636231
TI  - Eskimo1 mutants of Arabidopsis are constitutively freezing-tolerant.
AB  - Temperate plants develop a greater ability to withstand freezing in response to a
      period of low but nonfreezing temperatures through a complex, adaptive process of
      cold acclimation. Very little is known about the signaling processes by which
      plants perceive the low temperature stimulus and transduce it into the nucleus to
      activate genes needed for increased freezing tolerance. To help understand the
      signaling processes, we have isolated mutants of Arabidopsis that are
      constitutively freezing-tolerant in the absence of cold acclimation. Freezing
      tolerance of wild-type Arabidopsis was increased from -5.5 degreesC to -12.6
      degreesC by cold acclimation whereas the freezing tolerance of 26 mutant lines
      ranged from -6.8 degreesC to -10.6 degreesC in the absence of acclimation. Plants
      with mutations at the eskimo1 (esk1) locus accumulated high levels of proline, a
      compatible osmolyte, but did not exhibit constitutively increased expression of
      several cold-regulated genes involved in freezing tolerance. RNA gel blot
      analysis suggested that proline accumulation in esk1 plants was mediated by
      regulation of transcript levels of genes involved in proline synthesis and
      degradation. The characterization of esk1 mutants and results from other mutants
      suggest that distinct signaling pathways activate different aspects of cold
      acclimation and that activation of one pathway can result in considerable
      freezing tolerance without activation of other pathways.

PMID- 9636232
TI  - The specific features of methionine biosynthesis and metabolism in plants.
AB  - Plants, unlike other higher eukaryotes, possess all the necessary enzymatic
      equipment for de novo synthesis of methionine, an amino acid that supports
      additional roles than simply serving as a building block for protein synthesis.
      This is because methionine is the immediate precursor of S-adenosylmethionine
      (AdoMet), which plays numerous roles of being the major methyl-group donor in
      transmethylation reactions and an intermediate in the biosynthesis of polyamines
      and of the phytohormone ethylene. In addition, AdoMet has regulatory function in
      plants behaving as an allosteric activator of threonine synthase. Among the
      AdoMet-dependent reactions occurring in plants, methylation of cytosine residues
      in DNA has raised recent interest because impediment of this function alters
      plant morphology and induces homeotic alterations in flower organs. Also, AdoMet
      metabolism seems somehow implicated in plant growth via an as yet fully
      understood link with plant-growth hormones such as cytokinins and auxin and in
      plant pathogen interactions. Because of this central role in cellular metabolism,
      a precise knowledge of the biosynthetic pathways that are responsible for
      homeostatic regulation of methionine and AdoMet in plants has practical
      implications, particularly in herbicide design.

PMID- 9636233
TI  - Mitochondrial localization of a NADP-dependent [corrected] isocitrate
      dehydrogenase isoenzyme by using the green fluorescent protein as a marker.
AB  - In this work, we describe the isolation of a new cDNA encoding an NADP-dependent
      isocitrate dehydrogenase (ICDH). The nucleotide sequence in its 5' region gives a
      deduced amino acid sequence indicative of a targeting peptide. However, even if
      this cDNA clearly encodes a noncytosolic ICDH, it is not possible to say from the
      targeting peptide sequence to which subcellular compartment the protein is
      addressed. To respond to this question, we have transformed tobacco plants with a
      construct containing the entire targeting signal-encoding sequence in front of a
      modified green fluorescent protein (GFP) gene. This construct was placed under
      the control of the cauliflower mosaic virus 35S promoter, and transgenic tobacco
      plants were regenerated. At the same time, and as a control, we also have
      transformed tobacco plants with the same construct but lacking the nucleotide
      sequence corresponding to the ICDH-targeting peptide, in which the GFP is
      retained in the cytoplasm. By optical and confocal microscopy of leaf epiderm and
      Western blot analyses, we show that the putative-targeting sequence encoded by
      the cDNA addresses the GFP exclusively into the mitochondria of plant cells.
      Therefore, we conclude that this cDNA encodes a mitochondrial ICDH.

PMID- 9636234
TI  - Gene-for-gene disease resistance without the hypersensitive response in
      Arabidopsis dnd1 mutant.
AB  - The cell death response known as the hypersensitive response (HR) is a central
      feature of gene-for-gene plant disease resistance. A mutant line of Arabidopsis
      thaliana was identified in which effective gene-for-gene resistance occurs
      despite the virtual absence of HR cell death. Plants mutated at the DND1 locus
      are defective in HR cell death but retain characteristic responses to avirulent
      Pseudomonas syringae such as induction of pathogenesis-related gene expression
      and strong restriction of pathogen growth. Mutant dnd1 plants also exhibit
      enhanced resistance against a broad spectrum of virulent fungal, bacterial, and
      viral pathogens. The resistance against virulent pathogens in dnd1 plants is
      quantitatively less strong and is differentiable from the gene-for-gene
      resistance mediated by resistance genes RPS2 and RPM1. Levels of salicylic acid
      compounds and mRNAs for pathogenesis-related genes are elevated constitutively in
      dnd1 plants. This constitutive induction of systemic acquired resistance may
      substitute for HR cell death in potentiating the stronger gene-for-gene defense
      response. Although cell death may contribute to defense signal transduction in
      wild-type plants, the dnd1 mutant demonstrates that strong restriction of
      pathogen growth can occur in the absence of extensive HR cell death in the gene
      for-gene resistance response of Arabidopsis against P. syringae.

PMID- 9636235
TI  - Histidine kinase activity of the ETR1 ethylene receptor from Arabidopsis.
AB  - ETR1 represents a prototypical ethylene receptor. Homologues of ETR1 have been
      identified in Arabidopsis as well as in other plant species, indicating that
      ethylene perception involves a family of receptors and that the mechanism of
      ethylene perception is conserved in plants. The amino-terminal half of ETR1
      contains a hydrophobic domain responsible for ethylene binding and membrane
      localization. The carboxyl-terminal half of the polypeptide contains domains with
      homology to histidine kinases and response regulators, signaling motifs
      originally identified in bacteria. The putative histidine kinase domain of ETR1
      was expressed in yeast as a fusion protein with glutathione S-transferase and
      affinity purified. Autophosphorylation of the purified fusion protein was
      observed on incubation with radiolabeled ATP. The incorporated phosphate was
      resistant to treatment with 3 M NaOH, but was sensitive to 1 M HCl, consistent
      with phosphorylation of histidine. Autophosphorylation was abolished by mutations
      that eliminated either the presumptive site of phosphorylation (His-353) or
      putative catalytic residues within the kinase domain. Truncations were used to
      delineate the region required for histidine kinase activity. An examination of
      cation requirements indicated that ETR1 requires Mn2+ for autophosphorylation.
      These results demonstrate that higher plants contain proteins with histidine
      kinase activity. Furthermore, these results indicate that aspects of ethylene
      signaling may be regulated by changes in histidine kinase activity of the
      receptor.

PMID- 9636236
TI  - The interspecific mass-density relationship and plant geometry.
AB  - We present an a priori theoretical framework for the interspecific allometric
      relationship between stand mass and plant population density. Our model predicts
      a slope of -1/3 between the logarithm of stand mass and the logarithm of stand
      density, thus conflicting with a previously assumed slope of -1/2. Our model
      rests on a heuristic separation of resource-limited living mass and structural
      mass in the plant body. We point out that because of similar resource
      requirements among plants of different sizes, a nonzero plant mass-density slope
      is primarily defined by structural mass. Specifically, the slope is a result of
      (i) the physical size-dependent relationship between stem width and height, (ii)
      foliage-dependent demands of conductance, and (iii) the cumulative nature of
      structural mass. The data support our model, both when the potential sampling
      bias of taxonomic relatedness is accounted for and when it is not. Independent
      contrasts analyses show that observed relationships among variables are not
      significantly different from the assumptions made to build the model or from its
      a priori predictions. We note that the dependence of the plant mass-density slope
      on the functions of structural mass provides a cause for the difference from the
      zero slope found in the animal population mass-density relationship; for the most
      part, animals do not have a comparable cumulative tissue type.

PMID- 9636237
TI  - Brain mechanisms of quantity are similar in 5-year-old children and adults.
AB  - Both 5-year-old children and adults determine the quantity of a number by the use
      of a similar parietal lobe mechanism. Event related potentials indicate that
      input from Arabic digits and from dot patterns reach areas involved in
      determining quantity about 200 ms after input. However, voluntary key presses
      indicating the relation of the input to the quantity five take almost three times
      as long in children. The ability to trace the networks of brain areas involved in
      the learning of school subjects should aid in the design and testing of
      educational methods.

PMID- 9636239
TI  - Neurotransmitter transporters: regulators of function and functional regulation.

PMID- 9636238
TI  - Local microdomain structure in the terminal extensions of betaA3- and betaB2
      crystallins.
AB  - PURPOSE: Although the crystal structures of the core domains of bovine betaB2
      crystallin have been determined and those of other betagamma-crystallins modeled,
      the positions of the N- and C-termini are not resolvable by X-ray
      crystallography. Here we model the possible structural organization of the
      terminal arms of mouse betaA3- and betaB2-crystallins and test this model against
      the results of partial proteolysis. METHODS: The secondary structure of the
      terminal extensions was predicted by 3 different methods, one a nearest-neighbor
      method modified to use overlapping sequence tripeptides. Recombinant betaA3- and
      betaB2-crystallins were expressed using baculovirus vectors in S. frugiperda Sf9
      cells. Crystallins were sequenced by the Edman degradation method. RESULTS: The N
      terminal extension of betaB2-crystallin includes a series of hydrophilic residues
      from Q-11 to Q-9 which have high propensity of a helical conformation. The N
      terminal arm of betaA3-crystallin is also predicted to have two helical segments,
      from Q-24 to E-20 and M-13 to A-12. Partial characterization of the baculovirus
      extract showed a thiol protease inhibited by leupeptin and E-64. As predicted by
      the model, recombinant betaB2-crystallin subjected to partial proteolysis was
      cleaved adjacent to the helical domain, while the N-terminal cleavage site in
      recombinant betaA3-crystallin was within 1 residue of an interhelical junction.
      Our model also predicts the products of partial proteolytic degradation of betaB2
      and betaA3-crystallins from human, rat, bovine and chicken lenses incubated with
      the protease m-calpain. CONCLUSIONS: These results suggest the existence of local
      microdomain structures in the N- and C-terminal extensions of betaA3- and betaB2
      crystallins, which appear to be more susceptible to proteolytic degradation in
      regions adjacent to these putative domains.

PMID- 9636240
TI  - Transmembrane Mg2+ currents and intracellular free Mg2+ concentration in
      Paramecium tetraurelia.
AB  - The properties of Mg2+ conductances in Paramecium tetraurelia were investigated
      under two-electrode voltage clamp. When bathed in physiological Mg2+
      concentrations (0.5 mm), depolarizing steps from rest elicited a prominent Mg2+
      specific current (IMg) that has been noted previously. The dependence of this
      current on extracellular Mg2+ approximated that of Mg2+-induced backward
      swimming, demonstrating that IMg contributes to normal membrane excitation and
      behavior in this ciliate. Closer analysis revealed that the Mg2+ current
      deactivated biphasically. While this might suggest the involvement of two Mg2+
      specific pathways, both tail-current components were affected similarly by
      current-specific mutations and they had similar ion selectivities, suggesting a
      common pathway. In contrast, a Mg2+ current activated upon hyperpolarization
      could be separated into three components. The first, IMg, had similar properties
      to the current activated upon depolarization. The second was a nonspecific
      divalent cation current (INS) that was revealed following suppression of IMg by
      eccentric mutation. The final current was relatively minor and was revealed
      following suppression of IMg and INS by obstinate A gene mutation. Reversal
      potential analyses suggested that IMg and INS define two intracellular
      compartments that contain, respectively, low (0.4 mM) and high (8 mM)
      concentrations of Mg2+. Measurement of intracellular free Mg2+ using the
      fluorescent dye, Mag-fura-2, suggested that bulk [Mg2+]i rests at around 0.4 mM
      in Paramecium.

PMID- 9636241
TI  - Electrophysiological study of chimeric sodium channels from heart and skeletal
      muscle.
AB  - The alpha-subunit cDNAs encoding voltage-sensitive sodium channels of human heart
      (hH1) and rat skeletal muscle (rSkM1) have been expressed in the tsA201 mammalian
      cell line, in which inactivation properties appear to be normal in contrast to
      Xenopus oocytes. A series of rSkM1/hH1 chimeric sodium channels has been
      evaluated to identify the domains of the alpha-subunits that are responsible for
      a set of electrophysiological differences between hH1 and rSkM1, namely,
      midpoints and slope factors of steady-state activation and inactivation,
      inactivation kinetics and recovery from inactivation kinetics and their voltage
      dependence. The phenotype of chimeric channels in which each hH1 domain was
      successively introduced into a rSkM1 alpha-subunit framework confirmed the
      following conclusions. (i) The D4 and or/C-ter. are responsible for the slow
      inactivation of hH1 sodium channels. (ii) Concerning the other differences
      between rSkM1 and hH1: steady-state activation and inactivation, kinetics of
      recovery from inactivation, the phenotypes are determined probably by more than
      one domain of the alpha-subunit.

PMID- 9636242
TI  - Flow-dependent activation of maxi K+ channels in apical membrane of rabbit
      connecting tubule.
AB  - The Ca2+-activated maxi K+ channel was found in the apical membrane of everted
      rabbit connecting tubule (CNT) with a patch-clamp technique. The mean number of
      open channels (NPo) was markedly increased from 0.007 +/- 0.004 to 0.189 +/-
      0.039 (n = 7) by stretching the patch membrane in a cell-attached configuration.
      This activation was suggested to be coupled with the stretch-activation of Ca2+
      permeable cation channels, because the maxi K+ channel was not stretch-activated
      in both the cell-attached configuration using Ca2+-free pipette and in the inside
      out one in the presence of 10 mm EGTA in the cytoplasmic side. The maxi K+
      channel was completely blocked by extracellular 1 microM charybdotoxin (CTX), but
      was not by cytoplasmic 33 microM arachidonic acid (AA). On the other hand, the
      low-conductance K+ channel, which was also found in the same membrane, was
      completely inhibited by 11 microM AA, but not by 1 microM CTX. The apical K+
      conductance in the CNT was estimated by the deflection of transepithelial voltage
      (DeltaVt) when luminal K+ concentration was increased from 5 to 15 mEq. When the
      tubule was perfused with hydraulic pressure of 0.5 KPa, the DeltaVt was only -0.
      7 +/- 0.4 mV. However, an increase in luminal fluid flow by increasing perfusion
      pressure to 1.5 KPa markedly enhanced DeltaVt to -9.4 +/- 0.9 mV. Luminal
      application of 1 microM CTX reduced the DeltaVt to -1.3 +/- 0.6 mV significantly
      in 6 tubules, whereas no significant change of DeltaVt was recorded by applying
      33 microM AA into the lumen of 5 tubules (DeltaVt = -7.2 +/- 0.5 mV in control
      vs. DeltaVt = -6.7 +/- 0.6 mV in AA). These results suggest that the Ca2+
      activated maxi K+ channel is responsible for flow-dependent K+ secretion by
      coupling with the stretch-activated Ca2+-permeable cation channel in the rabbit
      CNT.

PMID- 9636243
TI  - Effects of ATP-sensitive potassium channel regulators on chloride channels in the
      sarcoplasmic reticulum vesicles from rabbit skeletal muscle.
AB  - The lipid bilayer technique was used to examine the effects of the ATP-sensitive
      K+ channel inhibitor (glibenclamide) and openers (diazoxide, minoxidil and
      cromakalim) and Cl- channel activators (GABA and diazepam) on two types of
      chloride channels in the sarcoplasmic reticulum (SR) from rabbit skeletal muscle.
      Neither diazepam at 100 microM nor GABA at 150 microM had any significant effect
      on the conductance and kinetics of the 75 pS small chloride (SCl) channel. Unlike
      the 150 pS channel, the SCl channel is sensitive to cytoplasmic glibenclamide
      with Ki approximately 30 microM. Glibenclamide induced reversible decline in the
      values of current (maximal current amplitude, Imax and average mean current, I')
      and kinetic parameters (frequency of opening Fo, probability of the channel being
      open Po and mean open time, To, of the SCl channel. Glibenclamide increased mean
      closed time, Tc, and was a more potent blocker from the cytoplasmic side (cis)
      than from the luminal side (trans) of the channel. Diazoxide increased I', Po,
      and To in the absence of ATP and Mg2+ but it had no effect on Imax and also
      failed to activate or remove the glibenclamide- and ATP-induced inhibition of the
      SCl channel. Minoxidil induced a transient increase in I' followed by an
      inhibition of Imax, whereas cromakalim reduced Po and I' by increasing channel
      transitions to the closed state and reducing To without affecting Imax. The
      presence of diazoxide, minoxidil or cromakalim on the cytoplasmic side of the
      channel did not prevent [ATP]cis or [glibenclamide]cis from blocking the channel.
      The data suggest that the action(s) of these drugs are not due to their effects
      on the phosphorylation of the channel protein. The glibenclamide- and cromakalim
      induced effects on the SCl channel are mediated via a "flicker" type block
      mechanism. Modulation of the SCl channel by [diazoxide]cis and [glibenclamide]cis
      highlights the therapeutic potential of these drugs in regulating the Ca2+
      counter current through this channel.

PMID- 9636244
TI  - Tight junctions and the experimental modifications of lipid content.
AB  - Tight junctions (TJs) are cell-to-cell contacts made of strands, which appear as
      ridges on P faces and complementary furrows on E faces on freeze fracture
      replicas. Evidences and opinions on whether these strands are composed of either
      membrane-bound proteins or lipid micelles are somewhat varied. In the present
      work we alter the lipid composition of Madin-Darby canine kidney monolayers using
      a novel approach, while studying (i) their transepithelial electrical resistance,
      a parameter that depends on the degree of sealing of the TJs; (ii) the apical-to
      basolateral flux of 4 kD fluorescent dextran (JDEX), that reflects the
      permeability of the intercellular spaces; (iii) the ability of TJs to restrict
      apical-to-basolateral diffusion of membrane lipids; and (iv) the pattern of
      distribution of endogenous and transfected occludin, the sole membrane protein
      presently known to form part of the TJs. We show that changing the total
      composition of phospholipids, sphingolipids, cholesterol and the content of fatty
      acids, does not alter TER nor the structure of the strands. Interestingly,
      enrichment with linoleic acid increases the JDEX by 631%. The fact that this
      increase is not reflected in a decrease of TER, suggests that junctional strands
      do not act as simple resistive elements but may contain mobile translocating
      mechanisms.

PMID- 9636245
TI  - Chloride conductance and Pi transport are separate functions induced by the
      expression of NaPi-1 in Xenopus oocytes.
AB  - Expression of the protein NaPi-1 in Xenopus oocytes has previously been shown to
      induce an outwardly rectifying Cl- conductance (GCl), organic anion transport and
      Na+-dependent Pi-uptake. In the present study we investigated the relation
      between the NaPi-1 induced GCl and Pi-induced currents and transport. NaPi-1
      expression induced Pi-transport, which was not different at 1-20 ng/oocyte NaPi-1
      cRNA injection and was already maximal at 1-2 days after cRNA injection. In
      contrast, GCl was augmented at increased amounts of cRNA injection (1-20
      ng/oocyte) and over a five day expression period. Subsequently all experiments
      were performed on oocytes injected with 20 ng/oocytes cRNA. Pi-induced currents
      (Ip) could be observed in NaPi-1 expressing oocytes at high concentrations of Pi
      (>/= 1 mm Pi). The amplitudes of Ip correlated well with GCl. Ip was blocked by
      the Cl- channel blocker NPPB, partially Na+-dependent and completely abolished in
      Cl- free solution. In contrast, Pi-transport in NaPi-1 expressing oocytes was not
      NPPB sensitive, stronger depending on extracellular Na+ and weakly affected by Cl
      substitution. Endogenous Pi-uptake in water-injected oocytes amounted in all
      experiments to 30-50% of the Na+-dependent Pi-transport observed in NaPi-1
      expressing oocytes. The properties of the endogenous Pi-uptake system (Km for Pi
      > 1 mM; partial Na+- and Cl--dependence; lack of NPPB block) were similar to the
      NaPi-1 induced Pi-uptake, but no Ip could be recorded at Pi-concentrations </=3
      mM. In summary, the present data suggest that Ip does not reflect charge transfer
      related to Pi-uptake, but a Pi-mediated modulation of GCl.

PMID- 9636246
TI  - Differential effects of aldosterone and vasopressin on chloride fluxes in
      transimmortalized mouse cortical collecting duct cells.
AB  - The effects of aldosterone and vasopressin on Cl- transport were investigated in
      a mouse cortical collecting duct (mpkCCD) cell line derived from a transgenic
      mouse carrying the SV40 large T antigen driven by the proximal regulatory
      sequences of the L-pyruvate kinase gene. The cells had features of a tight
      epithelium and expressed the amiloride-sensitive sodium channel and the cystic
      fibrosis transmembrane conductance regulator (CFTR) genes. dD-arginine
      vasopressin (dDAVP) caused a rapid, dose-dependent, increase in short-circuit
      current (Isc). Experiments with ion channel blockers and apical ion substitution
      showed that the current represented amiloride-sensitive Na+ and 5-nitro-2-(3
      phenylpropylamino)benzoate-sensitive and glibenclamide-sensitive Cl- fluxes.
      Aldosterone (5 x 10(-7)M for 3 or 24 hr) stimulated Isc and apical-to-basal 22Na+
      flux by 3-fold. 36Cl- flux studies showed that dDAVP and aldosterone stimulated
      net Cl- reabsorption and that dDAVP potentiated the action of aldosterone on Cl-
      transport. Whereas aldosterone affected only the apical-to-basal 36Cl- flux,
      dDAVP mainly increased the apical-to-basal Cl- flux and the basal-to-apical flux
      of Cl- to a lesser extent. These results suggest that the discrete dDAVP-elicited
      Cl- secretion involves the CFTR and that dDAVP and aldosterone may affect in
      different ways the observed increased Cl- reabsorption in this model of mouse
      cultured cortical collecting duct cells.

PMID- 9636248
TI  - Introduction 

PMID- 9636247
TI  - A basolateral chloride conductance in rat lingual epithelium.
AB  - We used Ussing chamber measurements and whole-cell recordings to characterize a
      chloride conductance in rat lingual epithelium. Niflumic acid (NFA) and
      flufenamic acid (FFA), nonsteroidal anti-inflammatory aromatic compounds known to
      inhibit Cl- conductances in other tissues, reduced transepithelial short-circuit
      current (Isc) in the intact dorsal anterior rat tongue epithelium when added from
      the serosal side, and reduced whole-cell currents in rat fungiform taste cells.
      In both Ussing chamber and patch-clamp experiments, the effect of NFA was
      mimicked by replacement of bath Cl- with methanesulfonate or gluconate. In low Cl
      bath solution, the effect of NFA on whole-cell current was reduced. Replacement
      of bath Ca2+ with Ba2+ reduced the whole-cell Cl- current. We conclude that a
      Ca2+-activated Cl- conductance is likely present in the basolateral membrane of
      the rat lingual epithelium, and is present in the taste receptor cells from
      fungiform papillae. Further experiments will be required to identify the role of
      this conductance in taste transduction.

PMID- 9636250
TI  - Congenital heart disease visualized 

PMID- 9636249
TI  - Atrioventricular septal defect.

PMID- 9636251
TI  - The use of valved conduits in pediatric cardiac surgery.
AB  - Extracardiac valved conduits were introduced in 1966. Currently, both aortic and
      pulmonary homografts, preserved in antibiotic/nutrient solution or cryopreserved,
      are used. Conduits are implanted between the right ventricle and pulmonary
      artery, left ventricle and pulmonary artery, right atrium and right ventricle,
      and left atrium to left ventricle. Several factors can influence longevity of
      valved conduits: young age at implantation, small size of homograft, and
      immunological response. In the recent study from our department, we evaluated 405
      homografts implanted between 1971 and 1993 in patients who survived 90 days after
      surgery. Freedom from conduit replacement at 5 and 15 years was 84% and 31% (95%
      confidence limits: 80-88% and 19-43%), respectively. In multivariate analysis,
      there were only two predictors of conduit longevity: (1) conduits used at
      reoperation lasted less well than those used at original operation; and (2)
      conduits used earlier in the series lasted longer. Conduits may have to be
      replaced because of obstruction, conduit valve regurgitation,
      aneurysm/pseudoaneurysm, and endocarditis. Obstructed conduits are either
      replaced or outflow tract patch is used after removal of the conduit with or
      without pulmonary valve implantation. Current mortality of conduit insertion is
      low (5-6%). The risk of conduit replacement has also decreased in recent years to
      2-3.5%

PMID- 9636252
TI  - Tetralogy of Fallot with major aortopulmonary collaterals: early total repair.
AB  - Tetralogy of Fallot with pulmonary atresia and major aortopulmonary collaterals
      is a complex lesion distinguished by marked heterogeneity of pulmonary blood
      supply. Over the past two decades, investigators have developed various
      approaches to the management of this anomaly generally based on the concept of
      staged unifocalization of pulmonary blood supply. Although such approaches may
      represent an improvement on the natural history of this lesion, they remain
      inadequate for a substantial portion of patients born with tetralogy of Fallot
      and major aortopulmonary collaterals. Since 1992, our approach has been to
      perform one-stage complete unifocalization through a midline approach in all but
      a few extremely complicated patients. We aim to repair these patients early in
      infancy, with an emphasis on native tissue-tissue reconstruction, in order to
      optimize prospects for survival with a good functional outcome in as many
      patients as possible. In this review, we present our philosophy and our
      experience with unifocalization and repair in 72 patients.

PMID- 9636253
TI  - Arterial switch.
AB  - A relatively large spectra of anatomic variations are found within the unifying
      features of discordant ventriculoarterial connections. Variants that lend
      themselves to anatomic repair by the arterial switch operation are discussed,
      these include transposition of the great arteries with intact ventricular septum
      (TGA IVS), TGA associated with a ventricular septal defect (TGA VSD), double
      outlet right ventricle with subpulmonary VSD (DORV VSD), and TGA or DORV with VSD
      associated with coarctation. Double discordance with VSD, which is currently
      treated by double switch or Rastelli and atrial switch and which probably
      represents, in our department, the only remaining indication for atrial switch,
      is not discussed. Also, we exclude TGA associated with pulmonary stenosis, which
      is treated by Rastelli or REV operation.

PMID- 9636254
TI  - Current status of staged reconstruction for hypoplastic left heart syndrome.
AB  - Once considered a uniformly fatal condition, the outlook for newborns with
      hypoplastic left heart syndrome has been dramatically altered with staged
      reconstructive procedures. Refinements in operative technique and perioperative
      management have been largely responsible for this improved outlook. At the
      University of Michigan, 253 patients underwent the Norwood operation for classic
      hypoplastic left heart syndrome between January 1990 and November 1997. Hospital
      survival was 76%. Among patients considered at standard risk, survival was
      significantly higher (86%) than that for those patients with important risk
      factors (42%, p = 0.0001). Adverse survival was most strongly associated with
      significant associated noncardiac congenital conditions (p = 0.008) and severe
      preoperative obstruction to pulmonary venous return (p = 0.03). Survival
      following second-stage reconstruction with a hemi-Fontan or bidirectional Glenn
      procedure was 97%. The Fontan procedure has been completed in 94 of these
      patients with a hospital survival rate of 88%. Survival after the Fontan
      procedure improved significantly when the second stage of the reconstruction was
      completed with a hemi-Fontan procedure compared to a bidirectional Glenn (98% vs
      81%, p = 0.05). Among the patients considered at standard risk, actuarial
      survival was 70% at 5 years. The largest decrease in survival occurred in the
      first month of life and late deaths affected primarily those patients in the high
      risk group. Neurodevelopmental outcome studies demonstrated normal verbal and
      performance scores in the majority of patients. Staged reconstruction has
      significantly improved the intermediate-term outlook for patients with
      hypoplastic left heart syndrome. Factors addressing improvements in early first
      stage survival would be expected to add significantly to an overall improved late
      outcome.

PMID- 9636256
TI  - Teaching and evaluation in pediatric cardiology 

PMID- 9636255
TI  - The Fontan circulation: What have we learned? What to expect?
AB  - Our knowledge of the Fontan operation tends to indicate that it remains a
      palliative procedure for patients with a functionally single ventricle. There is
      a continuing attrition and the life expectancy of these patients is likely to be
      different from the life expectancy of a population of individuals having a
      biventricular circulation. This article is an essay on the rational approach for
      the future management of these patients. It is suggested that a better
      understanding of the continuing Fontan attrition and a more subtle way to predict
      outcomes of patients who do receive the Fontan could help in establishing better
      selection criteria and designing ways to prevent, delay, or treat the side
      effects of this late attrition.

PMID- 9636257
TI  - Neurological protection during cardiopulmonary bypass/deep hypothermia.

PMID- 9636258
TI  - Recognition and prevention of neurological complications in pediatric cardiac
      surgery.
AB  - Because of advances in surgical and cardiopulmonary bypass techniques it is now
      possible to definitively repair the vast majority of congenital heart disease in
      infancy or childhood. Although the majority of survivors do not have obvious
      cerebral sequelae, there is increasing disquiet about the high incidence of acute
      neurological events in the immediated postoperative period as well as evidence
      that at long-term follow-up there are subtle cognitive and motor deficits in
      many. Some children are more at risk of neurodevelopmental problems, either
      because of their cardiac (e.g. , extensive aortopulmonary collaterals) or
      cerebrovascular (e.g., the propensity to large vessel dissection) anatomy or
      because of genetic predisposition (e.g., to prothrombotic disorders). The
      incidence may vary with the surgery (e.g., the Fontan operation) and the
      cardiopulmonary bypass technique necessary to achieve an adequate technical
      repair (e.g., low or no flow at deep hypothermia). Recognition of the population
      at risk will lead to prevention of serious sequelae. Data collected in adults may
      be misleading, and many pediatric units have developed their own practice, but
      recent studies in animal models of child surgery and in children have produced
      some evidence to guide management to ensure the optimal cerebral as well as
      cardiac outcome. Pump flow should be maintained at least 30 ml/kg/min where
      possible, with inotropic support to maintain blood pressure if necessary. If pump
      flow must be lowered or circulatory arrest is essential, thorough cerebral
      cooling to deep hypothermic temperatures is mandatory; a pH-stat strategy may
      make this easier, but an alpha-stat strategy may be better in those operations
      that can be performed at moderate hypothermia. There is no evidence that the
      available pulsatile pumps offer an advantage. Tissue oxygenation may reach
      critical levels and a high hematocrit and oxygen tension may reduce the risk of
      significant hypoxia. There is a risk of embolization in children, which can be
      reduced with membrane oxygenators and careful monitoring; the role of arterial
      filtration remains controversial. The only protective agent that can currently be
      recommended is methylprednisolone to protect the spinal cord (e.g., in operations
      on the aortic arch). Further studies are needed in this important area.

PMID- 9636260
TI  - Current concepts in diagnosis and management of arrhythmias in infants and
      children 

PMID- 9636259
TI  - Utility of intraoperative transesophageal echocardiography in the assessment of
      residual cardiac defects.
AB  - To investigate the accuracy of immediate postbypass transesophageal
      echocardiography in the assessment of residual cardiac defects, we compared
      intraoperative transesophageal echocardiograms with intra/postoperative data in
      86 patients, aged 4 days to 30.7 years (median = 1.4 years), at risk for a total
      of 174 postoperative lesions: right (n = 55) or left (n = 26) ventricular outflow
      tract obstruction, ventricular septal defect (n = 65), aortic (n = 12) or mitral
      regurgitation (n = 8), or mitral stenosis (n = 8). Accuracy of intraoperative
      transesophageal echocardiography was evaluated based on comparison with (1)
      immediate post-bypass left (n = 4) or right (n = 9) ventricular outflow tract
      pressure gradients by pullback in the operating room, (2) direct surgical
      inspection of residual ventricular septal defects (n = 3), (3) pulmonary artery
      oxygen saturation (n = 49), (4) right ventricular outflow tract pullback gradient
      (n = 24), and (5) transthoracic echocardiogram (n = 51) performed within 40 days
      of surgery. The results indicate that intraoperative transesophageal
      echocardiography agreed with intra/postoperative data in 87% of patients at risk
      for right ventricular outflow tract obstruction, 96% at risk for left ventricular
      outflow tract obstruction, 97% at risk for ventricular septal defect, and 100% at
      risk for aortic regurgitation, mitral regurgitation, or mitral stenosis.
      Significant residual lesions led to immediate surgical revision in 11 cases: 3
      ventricular septal defects, 6 right and 2 left ventricular outflow tract
      obstructions. Of these, intraoperative transesophageal echocardiography confirmed
      and quantified suspected residual lesions in 7 and identified unsuspected lesions
      in 4 cases. Immediate postbypass transesophageal echocardiography proved reliable
      for assessing residual ventricular septal defect, mitral stenosis, and mitral or
      aortic regurgitation. Although accurate for assessment of the left and right
      ventricular outflow tracts in most patients, transesophageal echocardiography may
      not reliably reflect the severity of obstruction in all cases.

PMID- 9636261
TI  - Is surgical ligation of an accessory left superior vena cava always safe?
AB  - In patients considered for bidirectional Glenn or Fontan procedures, the
      association of left superior vena cava (LSVC) with ostial atresia of the coronary
      sinus should be diagnosed preoperatively in order to avoid surgical division or
      ligation of the LSVC and the negative effect of resulting coronary venous
      hypertension on myocardial perfusion. This report discusses the angiographic and
      hemodynamic features of LSVC when it is the only drainage route from a blind
      coronary sinus. A retrograde flow in the LSVC seen by Doppler ultrasonography
      should raise the suspicion of this diagnosis.

PMID- 9636262
TI  - Fenestration of extracardiac fontan and reversal of protein-losing enteropathy:
      case report.
AB  - We describe a patient with protein-losing enteropathy who presented 6 months
      after undergoing a modified Fontan operation. After failing to respond to medical
      therapy, the Fontan tunnel was fenestrated by catheter intervention with
      immediate improvement and resolution of hypoproteinemia and enteric protein loss.

PMID- 9636263
TI  - Unusual longevity without surgical intervention in complete transposition of the
      great arteries.
AB  - A case of unusual longevity to the age of 58 years is reported for a female
      patient with complete transposition of the great arteries. The association with a
      wide atrial septal defect with intact interventricular septum may have
      contributed to the long survival without surgery. Factors determining
      intercirculatory mixing and systemic oxygen saturation may be the high pulmonary
      flow, the location of the anatomic communication, sufficient hemoglobin
      concentration to allow an adequate level of systemic resistance and recirculated
      systemic flow, and the belated development of pulmonary vascular disease.

PMID- 9636264
TI  - Double-outlet right ventricle (tetralogy of Fallot type) associated with
      anomalous origin of the left coronary artery from the right pulmonary artery:
      report of successful total repair in a 2-month-Old infant.
AB  - The case reported herein demonstrates the rare association of double-outlet right
      ventricle (tetralogy of Fallot type) with anomalous origin of the left coronary
      artery from the pulmonary artery. It is the first reported successful total
      surgical repair in an infant.

PMID- 9636265
TI  - Development of superior vena cava to pulmonary vein fistulae following modified
      Fontan operation: case report of a rare anomaly and embolization therapy.
AB  - A patient with double inlet single ventricle, L-transposition of the great
      arteries, and atrioventricular valve regurgitation developed progressive heart
      failure necessitating modified Fontan operation at 16 months of age. The
      procedure included replacement of the atrioventricular valve and pacemaker
      insertion. Eight years following the operation, the patient developed progressive
      cyanosis. Catheterization confirmed the presence of fistulae from the superior
      vena cava and innominate vein to the pulmonary veins as the cause of cyanosis.
      Coil embolization of several fistulae was performed successfully at
      catheterization. Contributing factors for fistula formation in Fontan patients
      are discussed, and therapy is reviewed.

PMID- 9636266
TI  - Myocardial infarction in a 14-year-old girl, ten years after surgical correction
      of congenital coronary artery fistula.
AB  - Acute myocardial infarction developed in a 14-year-old girl, ten years after
      surgical repair of a coronary artery fistula. Angiography revealed fresh thrombus
      in the left anterior descending branch of the left coronary artery. The thrombus
      probably developed in the residual cul-de-sac of the occluded fistula. A
      procedure to abolish the cul-de-sac was then performed.

PMID- 9636267
TI  - Surgical treatment of aortic root aneurysm related to Marfan syndrome in early
      childhood.
AB  - The prognosis of Marfan syndrome in both adult and pediatric patients is
      primarily related to the cardiovascular complications. In infantile Marfan
      syndrome, although involvement of the mitral valve is the most frequently
      encountered cardiovascular lesion, the aortic root can be more worrisome because
      of its excessive dilatation, leading to aortic insufficiency or dissection. If
      the role of elective surgery is relatively well defined for adult patients, it is
      still debated during childhood. We report two patients, aged 22 months and 5
      years, each presenting an aortic root aneurysm related to Marfan syndrome, and
      each treated with the Bentall procedure without specific age-related mortality or
      morbidity. These two patients experienced normal growth and were free of any
      complication for a follow-up period of 8 and 2 years, respectively. More than an
      absolute value of the aortic root dimension, it is the conjunction of the rate of
      progression of the aortic root dilatation, the degree and the duration of the
      aortic valve regurgitation, and its resulting left ventricular dysfunction that
      must be taken into consideration in choosing the surgical option.

PMID- 9636269
TI  - From other journals 

PMID- 9636268
TI  - Transient hypertrophic cardiomyopathy in neonates.

PMID- 9636271
TI  - Upcoming events in pediatric cardiology 

PMID- 9636270
TI  - Historical vignette: relief of right ventricular outflow tract obstruction.

PMID- 9636272
TI  - HIV protease inhibitors head to market.

PMID- 9636273
TI  - Recent advances in reproductive genetic technologies.
AB  - New possibilities for the diagnosis and treatment of reproductive and genetic
      disorders are becoming available as a result of a series of recent technical
      advances. Intracytoplasmic sperm injection (ICSI) allows treatment of numerous
      infertile men whose sperm cannot penetrate the egg to initiate fertilization.
      Molecular genetic testing provides clients of reproductive age with additional
      information that permits prevention of genetic diseases such as fragile X
      syndrome, the leading cause of inherited mental retardation. Preimplantation
      genetic testing (PGT) offers couples who carry genetic disorders the prospect of
      having children with a greatly decreased risk of initiating a pregnancy involving
      an affected individual. Flow-cytometric sperm separation offers a new, effective
      approach for prevention of X-linked genetic disorders. Two major causes of
      recurrent pregnancy loss (RPL) involve recurrent trisomies and immunological
      disorders. Of the latter, 70% of studied populations of patients can attain live
      births with simple treatment protocols. Maternal serum assays involving multiple
      markers reduce both false positives and false negatives in detection of
      trisomies. Despite these advances in research, many safe and effective methods of
      diagnosis and treatment remain under-utilized in the clinical arena.

PMID- 9636274
TI  - Design, expression, and initial characterization of MB1, a de novo protein
      enriched in essential amino acids.
AB  - Using recently emerging protein folding principles we have designed a protein
      enriched in the essential amino acids methionine, threonine, lysine and leucine.
      Our preliminary study of consensus residues (based on charge, hydrophobicity and
      volume) of natural alpha-helical bundle proteins indicated that the residues M,
      T, K, and L could be inserted in an alpha-helical bundle structure. We therefore
      attempted to create a stable de novo protein, highly enriched in these essential
      amino acids, that would adopt the alpha-helical bundle fold. The design process
      was an iterative one. The consensus residues (based on the properties profile)
      for bundle helices were found considering the four helices taken together,
      helices I to IV individually, or only their N- and C-termini. Using these data,
      the helices in our de novo protein were designed by inserting the residues M, T,
      K and L as often as possible at positions where their volume, hydrophobicity and
      charge match the consensus found in natural bundle helices. Short sequences of
      strong turn formers were used to join the helices and adjust the predicted p1 to
      7.7, while a number of local and global factors were used to refine our design.
      Further, the sequence was checked to eliminate various known protease targets in
      E. coli. The sequence of our de novo protein, MB1, is: MAT-EDMTDMMTTLFKTMQLLTK
      SEPTA-MDEATKTATTMKNHLQNLMQK-TKNKE DMTDMATTYFKTMQLLTK-TEPSA-MDEATKTATTMKNHLQNLMQK
      GVA+ ++ , where dashes separate long helices from short, turn forming linkers. A
      gene coding for this protein was assembled from synthetic oligonucleotides, then
      fused to the maltose binding protein gene under the control of a tac promoter.
      The fusion protein was expressed in E. coli, purified and cleaved to yield
      maltose binding protein and our de novo protein, MB1. MB1 was found to be
      helical, to have the expected molecular weight (11 kDa) and the expected content
      (57%) of the essential amino acids M, T, K and L.

PMID- 9636275
TI  - Production of recombinant bovine enterokinase catalytic subunit in Escherichia
      coli using the novel secretory fusion partner DsbA.
AB  - Enterokinase (EK) is a heterodimeric serine protease which plays a key role in
      initiating the proteolytic digestion cascade in the mammalian duodenum. The
      enzyme acts by converting trypsinogen to trypsin via a highly specific cleavage
      following the pentapeptide recognition sequence (Asp)4-Lys. This stringent site
      specificity gives EK great potential as a fusion protein cleavage reagent.
      Recently, a cDNA encoding the catalytic (light) chain of bovine enterokinase
      (EKL) was identified, characterized, and transiently expressed in mammalian COS
      cells. We report here the production of EKL in Escherichia coli by a novel
      secretory expression system that utilizes E. coli DsbA protein as an N-terminal
      fusion partner. The EKL cDNA was fused in-frame to the 3'-end of the coding
      sequence for DsbA, with the two domains of the fusion protein separated by a
      linker sequence encoding an enterokinase recognition site. Active, processed
      recombinant EKL (rEKL) was generated from this fusion protein via an
      autocatalytic cleavage reaction. The enzymatic properties of the bacterially
      produced rEKL were indistinguishable from the previously described COS-derived
      enzyme. Both forms of rEKL were capable of cleaving peptides, polypeptides and
      trypsinogen with the same specificity exhibited by the native heterodimeric
      enzyme purified from bovine duodena. Interestingly, rEKL activated trypsinogen
      poorly relative to the native heterodimeric enzyme, but was superior in its
      ability to cleave artificial fusion proteins containing the (Asp)4-Lys
      recognition sequence.

PMID- 9636276
TI  - A biotechnological method provides access to aggregation competent monomeric
      Alzheimer's 1-42 residue amyloid peptide.
AB  - Senile plaques, a neuropathological hallmark of Alzheimer's disease, consist
      primarily of insoluble aggregates of beta-amyloid peptide (A beta). A 42-residue
      peptide (A beta 1-42) appears to be the predominant form. In contrast to A beta 1
      40, A beta 1-42 is characterized by its extreme tendency to aggregate into fibers
      or precipitate. A tailored biotechnological method prevents aggregation of A beta
      1-42 monomers during its production. The method is based on a protein tail fused
      to the amino terminus of A beta. This tail leads to a high expression in E. coli,
      and a histidine affinity tag facilitates purification. Selective cleavage of the
      fusion tail is performed with cyanogen bromide by immobilizing the fusion protein
      on a reversed phase chromatography column. Cleavage then occurs only at the
      methionine positioned at the designed site but not at the methionine contained in
      the membrane anchor sequence of A beta. Furthermore, immobilization prevents
      aggregation of cleaved A beta. Elution from the HPLC column and all succeeding
      purification steps are optimized to preserve A beta 1-42 as a monomer. Solutions
      of monomeric A beta 1-42 spontaneously aggregate into fibers within hours. This
      permits the investigation of the transition of monomers into fibers and the
      correlation of physico-chemical properties with biological activities. Mutations
      of A beta 1-42 at position 35 influence the aggregation properties. Wild-type A
      beta 1-42 with methionine at position 35 has similar properties as A beta with a
      methionine sulfoxide residue. The fiber formation tendency, however, is reduced
      when position 35 is occupied by a glutamine, serine, leucine, or a glutamic acid
      residue.

PMID- 9636277
TI  - Double replacement gene targeting for the production of a series of mouse strains
      with different prion protein gene alterations.
AB  - We have developed a double replacement gene targeting strategy which enables the
      production of a series of mouse strains bearing different subtle alterations to
      endogenous genes. This is a two-step process in which a region of the gene of
      interest is first replaced with a selectable marker to produce an inactivated
      allele, which is then re-targeted with a second vector to reconstruct the
      inactivated allele, concomitantly introducing an engineered mutation. Five
      independent embryonic stem cell lines have been produced bearing different
      targeted alterations to the prion protein gene, including one which raises the
      level of expression. We have constructed mice bearing the codon 101 proline to
      leucine substitution linked to the human familial prion disease, Gerstmann
      Straussler-Scheinker syndrome. We anticipate that this procedure will have
      applications to the study of human inherited diseases and the development of
      therapies.

PMID- 9636278
TI  - Transovarian transmission of a foreign gene in the silkworm, Bombyx mori, by
      Autographa californica nuclear polyhedrosis virus.
AB  - We introduced a firefly luciferase gene, expressed under control of Drosophila
      heat shock protein gene promoter, into Autographa californica nuclear
      polyhedrosis virus (AcNPV). When the 5th instar larvae of the silkworm, Bombyx
      mori, were inoculated with the recombinant virus, luciferase activities were
      detected in the virus-infected larvae and pupae, and in the newly hatched larvae
      of the next generation. PCR amplification and Southern blot hybridization
      analysis demonstrated that the luciferase gene was transmitted through at least
      the F2 generation. In addition, the V-cathepsin gene, encoding a cysteine
      protease of AcNPV, was also detected in the DNA of all individuals of the F2
      generation. These results show that AcNPV can be utilized as vector for the
      transovarian transmission of foreign genes in the silkworm.

PMID- 9636279
TI  - Using viral genes to fight disease.

PMID- 9636280
TI  - Obesity: where less is more.

PMID- 9636281
TI  - Eukaryotic virus display: engineering the major surface glycoprotein of the
      Autographa californica nuclear polyhedrosis virus (AcNPV) for the presentation of
      foreign proteins on the virus surface.
AB  - We describe the development of the baculovirus Autographa californica nuclear
      polyhedrosis virus (AcNPV) as a vector for the display of distinct proteins on
      the viral surface in a manner that is analogous to the established bacterial
      "phage display" systems. As a model system, the marker gene encoding the 26kDa
      protein glutathione-S-transferase (GST) was used to construct several fusions
      with the major baculovirus glycoprotein gp64 gene. Following expression in
      Spodoptera frugiperda (Sf9) cells, the yield and cellular distribution of each
      GST-gp64 protein was assessed by Western blot of both cell and supernatant
      fractions. One fusion, in which GST was inserted between the leader peptide and
      the nature protein, was found to be efficiently secreted into the cell medium. In
      the context of expression of the full length gp64, the hybrid GST-gp64 was shown
      by immunogold labelling to be incorporated onto the virion surface. In addition,
      the affinity purification of the soluble transmembrane gp64-GST fusion protein
      resulted in the co-purification of wild type gp64 suggesting that co
      oligomerization of the GST-tagged fusion and the wild type molecule was the basis
      for virion incorporation. The HIV major surface glycoprotein, gp120 was also
      efficiently displayed in functional form on the viral surface following fusion to
      the amino terminus of gp64. A general expression vector, pAcSurf-2, was
      constructed in which multiple cloning sites were positioned in-phase between the
      gp64 signal sequence and the sequence encoding the mature protein under the
      control of the polyhedrin promoter.

PMID- 9636282
TI  - "Horizontal" gene transfer from a transgenic potato line to a bacterial pathogen
      (Erwinia chrysanthemi) occurs--if at all--at an extremely low frequency.
AB  - The frequency of possible "horizontal" gene transfer between a plant and a
      tightly associated bacterial pathogen was studied in a model system consisting of
      transgenic Solanum tuberosum, containing a beta-lactamase gene linked to a pBR322
      origin of replication, and Erwinia chrysanthemi. This experimental system offers
      optimal conditions for the detection of possible horizontal gene transfer events,
      even when they occur at very low frequency. Horizontal gene transfer was not
      detected under conditions mimicking a "natural" infection. The gradual, stepwise
      alteration of artificial, positive control conditions to idealized natural
      conditions, however, allowed the characterization of factors that affected gene
      transfer, and revealed a gradual decrease of the gene transfer frequency from 6.3
      x 10(-2) under optimal control conditions to a calculated 2.0 x 10(-17) under
      idealized natural conditions. These data, in combination with other published
      studies, argue that horizontal gene transfer is so rare as to be essentially
      irrelevant to any realistic assessment of the risk involved in release
      experiments involving transgenic plants.

PMID- 9636283
TI  - The intracellular domain of the rabbit prolactin receptor is able to promote the
      secretion of a passenger protein via an unusual secretory pathway in lepidopteran
      cells.
AB  - We have previously shown that the intracellular domain of the rabbit prolactin
      receptor (rbPRL-R), lacking typical signal sequences, was very efficiently
      secreted into the culture medium when expressed in the baculovirus-insect cell
      system. We have sought to take advantage of this characteristic for secreting
      cytoplasmic or nuclear proteins. We have constructed a series of recombinant
      viruses expressing a foreign gene product fused to the intracellular domain of
      rbPRL-R. Two passenger genes were used, one encoding a cytoplasmic protein
      (cyclin B) and the other a nuclear protein (cyclin A). The intracellular domain
      of rbPRL-R was able to promote the export of these two chimeric proteins with a
      very high efficiency. This new system should prove useful for secretion of
      proteins which do not require the post-translational modifications of the
      classical secretory pathway to be fully active.

PMID- 9636284
TI  - Human stress protein hsp70: overexpression in E coli, purification and
      characterization.
AB  - The gene encoding the stress-inducible member of human heat shock protein hsp70,
      was expressed in E. coli using the bacteriophage T7 RNA polymerase-based gene
      expression system. Recombinant hsp70 (R-hsp70) was purified from inclusion bodies
      after solubilization and refolding, using a combination of ATP-agarose affinity
      chromatography and ion-exchange chromatography. R-hsp70 was shown to be monomeric
      and free of its structurally similar E. coli counterpart, DnaK. In addition, R
      hsp70 is functional as demonstrated by its ability to bind to peptides and to
      ATP. The availability of pure, correctly folded R-hsp70 in sufficient quantity
      will assist in the structural and functional characterization of hsp70.
      Furthermore, an understanding of the cytoprotective function of hsp70 and its
      role in immune responses during infections will be facilitated by the
      availability of pure R-hsp70.

PMID- 9636285
TI  - Redox state of single chain Fv fragments targeted to the endoplasmic reticulum,
      cytosol and mitochondria.
AB  - In this paper we have engineered the targeting of ScFv fragments to mitochondria
      and demonstrated that this can occur efficiently. This extends the range of
      subcellular compartments where antibody domains can be targeted in order to
      interfere with the action of the corresponding antigen. Moreover, we have
      compared the redox state of ScFv fragments targeted to the secretory compartment,
      the cytosol and the mitochondria, and demonstrated that cysteine residues in ScFv
      targeted to the secretory compartments and to the mitochondria are oxidized. On
      the contrary, cytosolic antibody domains are expressed in a reduced state, which
      is probably the reason for their lower expression levels. These pitfalls,
      however, do not prevent their successful utilization for intracellular
      immunization.

PMID- 9636286
TI  - Mammalian cell technology: secretion on demand.

PMID- 9636287
TI  - Pig hearts in the clinic next year?

PMID- 9636288
TI  - Pinning down a moving target: a standard HIV.

PMID- 9636289
TI  - Nervous excitement over neurotrophic factors.

PMID- 9636290
TI  - Biotechnology of breadmaking: unraveling and manipulating the multi-protein
      gluten complex.
AB  - Breadmaking is one of humankind's oldest technologies, being established some
      4,000 years ago. The ability to make leavened bread depends largely on the visco
      elastic properties conferred to wheat doughs by the gluten proteins. These allow
      the entrapment of carbon dioxide released by the yeast, giving rise to a light
      porous structure. One group of gluten proteins, the high molecular weight (HMW)
      subunits, are largely responsible for gluten elasticity, and variation in their
      amount and composition is associated with differences in elasticity (and hence
      quality) between various types of wheat. These proteins form elastomeric polymers
      stabilized by inter-chain disulphide bonds, and detailed studies of their
      structures have led to models for the mechanism of elasticity. This work has also
      provided a basis for direct improvement of wheat quality by transformation with
      additional HMW subunit genes.

PMID- 9636291
TI  - Regulated secretion of prolactin by the mouse insulinoma cell line beta TC-3.
AB  - Our aim is to use cultured cells capable of regulated protein secretion for the
      production of recombinant proteins that require particular types of post
      translational modifications. Here we have generated a stable transfected beta TC
      3 cell line, beta TC-IPR9, that secretes high levels of recombinant prolactin.
      Transfected cells synthesize both the 27 kDa glycosylated and a 23 kDa
      nonglycosylated prolactin; the 23 kDa nonglycosylated species was secreted
      preferentially when cells were placed in secretion medium containing
      isobutylmethylxanthine (IBMX) and high concentrations of glucose, K+, and Ca2+.
      When the cells were cultured in medium containing low concentrations of glucose,
      K+, and Ca2+, most of the prolactin and insulin were not secreted; much of the
      prolactin was proteolytically converted to a 16 kDa form. Within the first 30
      minutes after transferring the cells to medium containing secretagogues there was
      a 20-fold increase in the rate of secretion of prolactin; all of the 16 kDa
      species was secreted. The recombinant cells could be cycled several times between
      medium in which prolactin was biosynthesized and medium in which it was secreted.
      Preferential secretion of proteolytically processed prolactin in a medium without
      contaminating proteins offers an example of the advantage of this technology for
      production of other recombinant proteins.

PMID- 9636292
TI  - Engineered chimeric streptavidin tetramers as novel tools for bioseparations and
      drug delivery.
AB  - We report the construction of chimeric streptavidin tetramers that are composed
      of subunits of both wild-type (WT) streptavidin and genetically-engineered
      streptavidin variants designed for enhanced bioseparation and drug delivery
      performance. Subunit mixing is accomplished by guanidine thiocyanateinduced
      denaturation of an equimolar mixture of WT streptavidin and the respective site
      directed mutant, followed by renaturation and reassociation of mixed tetramers.
      In the first example, we demonstrate the mixing of WT subunits with an Asn49Cys
      (N49C) mutant. The WT/n49C tetramers can be used for site-specific and
      stoichiometric attachment of therapeutics/imaging agents or targeting proteins
      through the genetically-engineered thiol while retaining unhindered access to
      biotin-binding at the WT subunits. Second, we demonstrate that the His127Cys
      mutation (H127C) results in a streptavidin mutant that forms a disulfide-linked
      dimer under non-reducing conditions. Mixing of H127C and WT streptavidin subunits
      results in chimeric tetramers where both the stoichiometry (WT:H127C::1:1) and
      subunit architecture is controlled by the unique disulfide bridge engineered into
      H127C. In the third example, WT subunits were mixed with the subunits of a site
      directed mutant, Trp120Ala (W120A), which displays a biotin dissociation constant
      that is enhanced by more than 10(4) compared to WT streptavidin. The W120 biotin
      binding affinity is sufficiently high (Ka approximately equal to 10(7) M-1) to
      immobilize the mutant on a biotinagarose affinity chromatography column, but the
      engineered off-rate allows for facile elution with excess biotin at physiological
      pH, whereas WT streptavidin is irreversibly immobilized on the column. We
      demonstrate that the purified WT/W120A chimeric tetramers combine the advantages
      of both subunits, allowing for irreversible immobilization of biotinylated
      targets at the WT subunit, while retaining the reversible separation capabilities
      of the W120A subunits via biotin-agarose affinity chromatography.

PMID- 9636293
TI  - Transdermal delivery of heparin by skin electroporation.
AB  - Therapeutic uses of compounds produced by biotechnology are presently limited by
      the lack of noninvasive methods for continuous administration of biologically
      active macromolecules. Transdermal delivery would be an attractive solution,
      except macromolecules have not previously been delivered clinically across human
      skin at therapeutic rates. To increase transport of a highly-charged
      macromolecule (heparin), high-voltage pulses believed to cause electroporation
      were applied to skin. Using this approach, transdermal heparin transport across
      human skin in vitro occurred at therapeutic rates (100-500 micrograms/cm2h),
      reported to be sufficient for systemic anticoagulation. In contrast, fluxes
      caused by low-voltage iontophoresis having the same time-averaged current were an
      order of magnitude lower. Heparin transported across the skin was biologically
      active, but with only one eighth the anticoagulant activity of heparin in the
      donor compartment due to preferential transport of small (less active) heparin
      molecules. Flux, activity, and transport number data together suggest that high
      voltage pulsing creates transient changes in skin microstructure which do not
      occur during iontophoresis. Safety issues are discussed.

PMID- 9636294
TI  - A high capacity assay for inhibitors of human papillomavirus DNA replication.
AB  - The discovery of antiviral compounds against human papillomaviruses (HPV) has
      been hindered by the difficulties in culturing virus in vitro or assaying stable
      HPV DNA replication. However, plasmids containing the HPV replication origin
      replicate transiently upon co-transfection with HPV E1 and E2 expression vectors.
      We have adapted this assay using secreted alkaline phosphatase (SAP) as a
      reporter for rapid analysis of DNA copy number. Use of the SV40 early promoter in
      controlling SAP expression was critical in ensuring both a strong signal and copy
      number dependence: the stronger beta-actin promotor inhibited replication, while
      the weaker SV40 late promoter yielded very low levels of SAP. The precise
      configuration of the E1 and E2 expression vectors also was critical, most pre
      existing vectors did not support efficient replication and SAP secretion. The
      extent of DNA replication and SAP secretion were both proportional to the amount
      of E1/E2 vector used in transfections; under optimal conditions SAP increased 100
      fold during replication. The assay has been developed for compound screening in
      96-well plates and several inhibitors have been identified. Quantitative Southern
      blot analysis has shown that most of these inhibit HPV DNA replication rather
      than SAP accumulation or activity, and several are under test in models of viral
      replication. The assay also provides a rapid system for functional analysis of
      the HPV E1, E2 genes and the replication origin.

PMID- 9636295
TI  - A generic method for expression and use of "tagged" soluble versions of cell
      surface receptors.
AB  - A general method for expression, purification, immobilization, detection and
      radiolabeling of extracellular domains (ECD) of type I membrane proteins. The
      type I interleukin-1 receptor (IL-1RtI), the alpha-subunit of interleukin-2
      receptor (IL-2R alpha) and E-selectin are used as illustrative examples of cell
      surface receptors. DNA encoding the ECD of the proteins are fused at their 3' end
      to a chimeric DNA which serves to generically "tag" the recombinant ECD. The
      resulting fusion protein contains a substrate sequence for protein kinase-A (PKA)
      adjacent to the signal sequence from human placental alkaline phosphatase (HPAP),
      The HPAP signal sequence directs the formation of the phosphatidylinositol-glycan
      (PI-G) anchorage of the protein at the cell surface. When these chimeric genes
      are expressed in CHO cells, the ECDs are detected on the cell surface and can be
      released by treatment with phosphatidylinositol-specific phospholipase-C (PI
      PLC). Based on protein processing known to occur for native HPAP, twenty amino
      acids from the HPAP signal sequence remain at the C-terminus of the ECD. A high
      affinity monoclonal antibody was generated against this common epitope. This
      antibody can be used to detect, purify and immobilize the ECDs. In addition, the
      ECDs can be radiolabeled with 32P by treatment with PKA and maintain the ability
      to bind their natural ligands. This "tagging" method has been successfully
      applied to many other type I proteins which serve as cell surface receptors.

PMID- 9636296
TI  - Rapid assay of phage-derived recombinant human fabs as bispecific antibodies.
AB  - Specific anti-tumor and anti-viral activities can be conferred on lymphocytic and
      myeloid effector cells by retargeting them with bispecific antibodies. These are
      antibodies which possess an anti-target binding region and a region capable of
      binding specific effector cell surface markers. For the rapid evaluation of
      recombinant human Fabs as bispecific antibodies, we have constructed a vector
      that allows for the conversion of Fabs into protein A fusion proteins. These can
      be used to generate bispecific antibodies when complexed to appropriate anti
      effector cell immunoglobulins. As a model system, a protein A fusion derivative
      of a human recombinant anti-herpes simplex virus (HSV) Fab was constructed and
      complexed to OKT3, a T cell-activating antibody specific for CD3. This complex
      reduced HSV-2 yields in infected cells by about three logs relative to controls
      when incubated on HSV-2-infected cell monolayers in the presence of IL-2
      activated lymphocytes. The system described allows for the rapid evaluation of
      recombinant human Fabs as bispecific antibodies for therapeutic applications. In
      addition, Fab-protein A fusion proteins can be used in ELISA and other immuno
      assays with increased sensitivity.

PMID- 9636297
TI  - Expression of the human muscarinic receptor gene m2 in Dictyostelium discoideum.
AB  - We have expressed a functional human muscarinic M2 receptor, under the control of
      the homologous discoidin I gamma promoter, in the cellular slime mold
      Dictyostelium discoideum. The use of a contact site A leader peptide ensured
      insertion of the newly synthesized receptor protein into the plasma membrane. Due
      to the characteristics of the discoidin I gamma promoter, the M2 receptor is
      expressed during late growth and early development. The heterologously expressed
      M2 receptors show binding characteristics similar to authentic receptors.
      Membranes as well as whole cells can be used in ligand binding assays.

PMID- 9636298
TI  - Expression of active, secreted human prostate-specific antigen by recombinant
      baculovirus-infected insect cells on a pilot-scale.
AB  - We have expressed human prostate-specific antigen (PSA) on a pilot-scale in
      Spodoptera frugiperda Sf9 insect cells using recombinant baculovirus system.
      Infected cells secreted PSA into culture medium at a concentration of 2-4 mg per
      liter. PSA was expressed both in active and inactive forms which were separated
      in a final purification step using cation-exchange chromatography eluted with a
      low salt gradient. The N-terminus of active PSA was correctly cleaved; two amino
      acids of the propeptide remained, however, at the N-terminus of the inactive PSA.
      Purified recombinant PSA showed a chymotrypsin-like activity with the synthetic
      substrate MeO-Suc-Arg-Pro-Tyr-pNA, but did not have a trypsin-like activity when
      Pro-Phe-Arg-pNA was used. The molecular mass of active PSA was 31.0 kDa in
      reduced SDS-PAGE, 26.0 kDa in nonreduced SDS-PAGE and 26.5 kDa in ion spray mass
      spectrometry. The active protein formed complexes with alpha 1-antichymotrypsin
      (ACT) and alpha 2-macroglobulin (alpha 2M) in vitro similar to the commercial PSA
      purified from human seminal fluid.

PMID- 9636299
TI  - A new use for the mycoprotein organism.

PMID- 9636300
TI  - The many faces of IL-12.

PMID- 9636301
TI  - The cost of delivering drugs without needles.

PMID- 9636302
TI  - Therapeutic applications of heat shock proteins.

PMID- 9636303
TI  - Capillary electrophoresis-based immunoassays.

PMID- 9636304
TI  - Mammary gland expression of transgenes and the potential for altering the
      properties of milk.
AB  - Transgenic animals are a useful in vivo experimental model for assessing the
      ability and impact of foreign gene expression in a biological system. Transgenic
      mice are most commonly used, while transgenic sheep, goats, pigs and cows have
      also been developed for specific, "applied" purposes. Most of the work directed
      at targeting expression of transgenes to the mammary gland of an animal, by using
      a milk gene promoter, has been with the intent of either studying promoter
      function or recovering the desired protein from the milk. Transgenic technology
      can also be used to alter the functional and physical properties of milk
      resulting in novel manufacturing properties. The properties of milk have been
      altered by adding a new protein with the aim of improving the milk, not of
      recovering the protein for other uses.

PMID- 9636306
TI  - The yeast tribrid system--genetic detection of trans-phosphorylated ITAM-SH2
      interactions.
AB  - Protein-protein interactions are often dependent on the post-translational
      modification of one component of a complex. To facilitate the study of these
      interactions in signal transduction, we have developed the yeast tribrid system,
      a modification of the yeast two-hybrid system. We demonstrate that the
      interactions are dependent upon the presence of a tyrosine kinase, an SH2 domain
      and a tyrosine containing substrate. Using the gamma subunit of the high-affinity
      IgE receptor, Fc epsilon RI, this approach has been used to isolate a novel SH2
      containing family member. The mRNA encoding this novel protein is differentially
      expressed in rat tissues. The yeast tribrid system can be readily adapted for the
      characterization of novel tyrosine kinases or substrates, as well as the study of
      protein-protein interactions which involve other post-translational
      modifications.

PMID- 9636307
TI  - Fusarium graminearum A 3/5 as a novel host for heterologous protein production.
AB  - We describe a novel fungal expression system which utilizes the Quorn myco
      protein fungus Fusarium graminearum A 3/5. A transformation system was developed
      for F. graminearum and was used to introduce the coding and regulatory regions of
      a trypsin gene from Fusarium oxysporum. The protein was efficiently expressed,
      processed and secreted by the recombinant host strain. In addition, the promoter
      and terminator of the F. oxysporum trypsin gene have been successfully utilized
      to drive the expression of a cellulase gene from Scytalidium thermophilum and a
      lipase gene from Thermomyces lanuginosus in F. graminearum.

PMID- 9636308
TI  - Expression of the rabies virus glycoprotein in transgenic tomatoes.
AB  - We have engineered tomato plants (Lycopersicon esculentum Mill var. UC82b) to
      express a gene for the glycoprotein (G-protein), which coats the outer surface of
      the rabies virus. The recombinant constructs contained the G-protein gene from
      the ERA strain of rabies virus, including the signal peptide, under the control
      of the 35S promoter of cauliflower mosaic virus. Plants were transformed by
      Agrobacterium tumefaciens-mediated transformation of cotyledons and tissue
      culture on selective media. PCR confirmed the presence of the G-protein gene in
      plants surviving selection. Northern blot analysis indicated that RNA of the
      appropriate molecular weight was produced in both leaves and fruit of the
      transgenic plants. The recombinant G-protein was immunoprecipitated and detected
      by Western blot from leaves and fruit using different antisera. The G-protein
      expressed in tomato appeared as two distinct bands with apparent molecular mass
      of 62 and 60 kDa as compared to the 66 kDa observed for G-protein from virus
      grown in BHK cells. Electron microscopy of leaf tissue using immunogold-labeling
      and antisera specific for rabies G-protein showed localization of the G-protein
      to the Golgi bodies, vesicles, plasmalemma and cell walls of vascular parenchyma
      cells. In light of our previous demonstration that orally administered rabies G
      protein from the same ERA strain elicits protective immunity in animals, these
      transgenic plants should provide a valuable tool for the development of edible
      oral vaccines.

PMID- 9636309
TI  - Preparative scale purification of recombinant proteins to clinical grade by
      isotachophoresis.
AB  - An electrophoretic procedure based on isotachophoresis has been developed for
      protein purification on a preparative scale in the 10 to 500 mg range. The system
      is simple, uses well understood physical properties, does not need ampholyte
      spacers and is able to produce sterile products of clinical grade. We demonstrate
      the applicability of this apparatus for the purification of denatured recombinant
      proteins and complex mixtures of proteins. The system may also be used for both
      cationic and anionic purification of proteins in their native form. The system is
      scalable from analytical to preparative protein loads at consistently high
      protein yields and purity levels. Total protein loads may vary as much as 1000
      fold with the use of interchangeable columns of varying diameter and constant
      length. At both preparative and analytical scales concentration of products at
      greater than 20 mg/ml are obtainable. Toxicological considerations are addressed
      with assays for endotoxin, acrylamide and SDS concentrations, as well as the
      prevention of covalent protein modification.

PMID- 9636310
TI  - Therapeutic peptides: the devil is in the details.

PMID- 9636311
TI  - Biotechnology and new integrated pest management approaches.
AB  - Area-wide pest management technologies will take on new appearances as the drive
      to eliminate and/or greatly reduce the use of chemical pesticides increases. The
      use of genetically altered insects has the most potential for successfully
      displacing certain pesticides, although the development of genetic engineering
      technologies for agricultural pest species is still in its infancy.
      Transformation vectors need to be developed as do transformation methodologies.
      Here we report the possibility of developing an interspecies vector and discuss
      ways in which such a vector could be used successfully in an integrated pest
      management system. If such an approach were developed, it could be utilized with
      other alternative methods, thereby providing a safe, ecologically sound means of
      controlling insect pests without damaging the agricultural economy.

PMID- 9636312
TI  - Homologous expression and purification of mutants of an essential protein by
      reverse epitope-tagging.
AB  - Purification of mutant enzymes is a prime requirement of biophysical and
      biochemical studies. Our investigations on the essential Escherichia coli enzyme
      glutaminyl-tRNA synthetase demand mutant enzymes free of any wild-type protein
      contamination. However, as it is not possible to express noncomplementing mutant
      enzymes in an E. coli glnS-deletion strain, we developed a novel strategy to
      address these problems. Instead of following the common tactic of epitope-tagging
      the mutant protein of interest on an extrachromosomal genetic element, we fused a
      reporter epitope to the 5' end of the chromosomal glnS-gene copy: this is
      referred to as 'reverse epitope-tagging.' The corresponding strain, E. coli
      HAPPY101, displays a normal phenotype, and glutaminyl-tRNA synthetase is
      exclusively present as an epitope-tagged form in cell-free extracts. Here we
      report the use of E. coli HAPPY101 to express and purify a number of mutant
      glutaminyl-tRNA synthetases independently of their enzymatic activity. In this
      process, epitope-tagged wild-type protein is readily separated from mutant
      enzymes by conventional chromatographic methods. In addition, the absence of wild
      type can be monitored by immunodetection using a monoclonal antibody specific for
      the epitope. The strategy described here for expression and purification of an
      essential enzyme is not restricted to glutaminyl-tRNA synthetase and should be
      applicable to any essential enzyme that retains sufficient activity to sustain
      growth following reverse epitope-tagging.

PMID- 9636313
TI  - From proteins to proteomes: large scale protein identification by two-dimensional
      electrophoresis and amino acid analysis.
AB  - Separation and identification of proteins by two-dimensional (2-D)
      electrophoresis can be used for protein-based gene expression analysis. In this
      report single protein spots, from polyvinylidene difluoride blots of
      micropreparative E. coli 2-D gels, were rapidly and economically identified by
      matching their amino acid composition, estimated pI and molecular weight against
      all E. coli entries in the SWISS-PROT database. Thirty proteins from an E. coli 2
      D map were analyzed and identities assigned. Three of the proteins were unknown.
      By protein sequencing analysis, 20 of the 27 proteins were correctly identified.
      Importantly, correct identifications showed unambiguous "correct" score patterns.
      While incorrect protein identifications also showed distinctive score patterns,
      indicating that protein must be identified by other means. These techniques allow
      large-scale screening of the protein complement of simple organisms, or tissues
      in normal and disease states. The computer program described here is accessible
      via the World Wide Web at URL address (http:@expasy.hcuge.ch/).

PMID- 9636314
TI  - Characterization of human plasma glycoproteins separated by two-dimensional gel
      electrophoresis.
AB  - Purification of protein isoforms for the characterization of post-translational
      modifications, such as glycosylation, can be laborious and demanding. We report a
      means of determining monosaccharide composition and the identity of glycoproteins
      from a single spot on a two-dimensional (2-D) gel. The sensitivity of the method
      depends on the degree of glycosylation of the protein. We show that bovine fetuin
      can be analyzed and identified at the level of 100 pmol. 2-D reference maps
      enable quick identification of glycoprotein isoforms, and the nature of
      glycosylation differences. Human sera glycoforms were isolated by
      micropreparative 2-D PAGE using a narrow-range immobilized pH gradient. Single
      spots excised from one polyvinylidene difluoride blot of a 2-D gel were used
      sequentially for sialic acid analysis, neutral and amino sugar analysis, and
      finally amino acid analysis. The glycosylation variations in isoforms of human
      fetuin and alpha-1-antitrypsin were determined. The amino acid composition, in
      conjunction with protein pI and MW, successfully identified the glycoproteins.

PMID- 9636315
TI  - Transplanting two unique beta-glucanase catalytic activities into one
      multienzyme, which forms glucose.
AB  - Endo cellulases of plant pathogenic erwinias degrade cellulose as well as the
      cellulosic domains of barley (1-3,1-4)-beta-glucan. Depolymerization of the
      latter substrate is mainly caused by (1-3,1-4)-beta-glucanases, which hydrolyze
      (1-4)-beta glycosidic linkages adjacent to (1-3)-beta linkages. To construct an
      enzyme for efficient degradation of barley (1-3,1-4)-beta-glucan, the sequence
      encoding the catalytic domain and interdomain linker of the cellulase from
      Erwinia carotovora subspecies atroseptica was fused to that for the heat stable
      Bacillus hybrid, H(A12-M) delta Y13 (1-3,1-4)-beta glucanase. The chimeric enzyme
      secreted from Escherichia coli cells did not remain covalently assembled as
      judged by SDS-PAGE. However, the glycosylated and intact enzyme (denoted CELGLU)
      is secreted from the yeast Pichia pastoris. CELGLU exhibits both cellulase and (1
      3,1-4)-beta-glucanase catalytic activities, and was accordingly classified a true
      multienzyme. HPLC and NMR analyses revealed that among the products from CELGLU,
      di- and trimeric oligosaccharides were identical to those produced by the
      parental cellulase. Tetrameric oligosaccharides, derived from the (1-3,1-4)-beta
      glucanase activity of CELGLU, were further degraded by the cellulase moiety to
      yield glucose and trimers. Compared with the parental enzymes, CELGLU exhibits
      substantially higher Vmax for degradation of both soluble cellulose and barley (1
      3,1-4)-beta-glucan. These findings point to construction of multienzymes as an
      effective approach for engineering enzymes with novel characteristics.

PMID- 9636316
TI  - Production of a recombinant bovine enterokinase catalytic subunit in the
      methylotrophic yeast Pichia pastoris.
AB  - We describe the heterologous expression of a 26.3 kD protein containing the
      catalytic domain of bovine enterokinase (EKL) in the methylotrophic yeast Pichia
      pastoris. A highly active protein is secreted and glycosylated, and it has the
      native amino-terminus of EKL. The cDNA encoding EKL was cloned with the KEX2
      protease cleavage site following the alpha mating factor prepro secretion signal
      from Saccharomyces cerevisiae. The secreted EKL was easily purified from the few
      native proteins found in the P. pastoris fermentation supernatant, using ion
      exchange and affinity chromatography. The yield of the purified EKL was 6.3 mg
      per liter of fermentation culture. This is significantly higher than previous
      reports of expressions in E. coli and COS cells. The ability of this highly
      specific protease to cleave immediately after the carboxyl-terminal residue of
      the (Asp)4-Lys recognition sequence allows regeneration of native amino-terminal
      residues of recombinant proteins. Its application is demonstrated by the removal
      of thioredoxin (TrxA), and polyhistidine fusion partners from proteins of
      interest.

PMID- 9636317
TI  - Development of an expression strategy using a lytic phage to trigger explosive
      plasmid amplification and gene expression.
AB  - A novel plasmid-based expression strategy, exploiting two features of lytic
      bacteriophages, was developed in Lactococcus lactis. Components of this system
      include a phage origin of replication and phage expression signals, which were
      induced to high efficiency upon phage infection of the host. Phage-specific
      expression signals were cloned from phi 31 in a promoter-screening strategy using
      the lacZ gene from Streptococcus thermophilus. One clone exhibited a significant
      induction in beta-galactosidase production and concomitant increase in lacZ mRNA
      during the phi 31 infection cycle of the host. Molecular characterization of the
      cloned insert revealed 888 bp positioned near the phi 31 cos site. Primer
      extension analysis showed that transcription was induced approximately 20 min
      following phi 31 infection at four points, apparently organized in two sets of
      tandem promoters on the cloned phage insert. One of these middle phage promoters
      also showed a basal level of activity prior to phage infection. The phi 31
      promoter lacZ cassette was cloned into a low-copy-number vector plasmid
      containing the phi 31 origin of replication (ori31) and the resulting low-copy
      number plasmid exhibited negligible beta-galactosidase production in L. lactis.
      However, > 2,000 units were detected following a deliberate infection with phi
      31. A control expression plasmid without ori31 could only be induced to 85 units.
      The combination of these phage-inducible expression signals together with ori31
      functioned synergistically to drive rapid and high efficiency expression of a
      heterologous gene in L. lactis.

PMID- 9636318
TI  - Catalytical potency of beta-glucosidase from the extremophile Pyrococcus furiosus
      in glucoconjugate synthesis.
AB  - The extremely thermostable wild type and recombinant beta-glucosidases, from
      Pyrococcus furiosus, served as catalysts for the biotransformation of new
      glucoconjugates at elevated temperatures. In conversion experiments using the
      transglucosylation approach, the free or immobilized enzyme accepted primary and
      even tertiary organic alcohols, as well as primary and secondary artificial
      organosilicon alcohols, as aglycones. Cellobiose served as the glucose donor. The
      products obtained were purified by liquid chromatography and analyzed. Using beta
      glucosidase a wide variety of products were synthesized. Due to the very broad
      structural diversity of the aglycones linked to the 1-beta-O-D-glucose, this beta
      glucosidase seems to be a useful biocatalyst for regio- and stereoselective sugar
      derivative synthesis.

PMID- 9636319
TI  - Transgenic Indica rice breeding line IR58 expressing a synthetic cryIA(b) gene
      from Bacillus thuringiensis provides effective insect pest control.
AB  - The Indica rice breeding line IR58 was transformed by particle bombardment with a
      truncated version of a synthetic cryIA(b) gene from Bacillus thuringiensis. This
      gene is expressed under control of the CaMV 35S promoter and allows efficient
      production of the lepidopteran specific delta-endotoxin. R0, R1 and R2 generation
      plants displayed a significant insecticidal effect on several lepidopterous
      insect pests. Feeding studies showed mortality rates of up to 100% for two of the
      most destructive insect pests of rice in Asia, the yellow stem borer (Scirpophaga
      incertulas) and the striped stem borer (Chilo suppressalis), and feeding
      inhibition of the two leaffolder species Cnaphalocrocis medinalis and Marasmia
      patnalis. Introduction of stem borer resistance into the germplasm of an Indica
      rice breeding line now makes this agronomically important trait available for
      conventional rice breeding programs.

PMID- 9636320
TI  - Targeting gene expression to the wool follicle in transgenic sheep.
AB  - To establish the feasibility of overexpressing foreign genes in the wool
      follicle, transgenic sheep were produced by pronuclear microinjection of a DNA
      construct consisting of a mouse ultrahigh-sulfur keratin promoter linked to the
      bacterial chloramphenicol acetyl transferase (CAT) gene. Four of 31 lambs born
      were transgenic. The overall efficiency of transgenesis was 1.1% of zygotes
      injected and transferred. Two transgenic rams were mated to nontransgenic ewes,
      and both transmitted the gene to their offspring in Mendelian fashion. CAT
      expression was found in the skin of one G0 ram and in 9 out of 26 transgenic G1
      progeny. Two G1 lambs were sacrificed to study tissue specificity. Both had high
      levels of expression in skin but One had high expression in spleen and kidney
      with lower levels of expression in lung; the other had low expression in spleen,
      lung, and muscle. In situ hybridization demonstrated that transgene expression in
      the skin was confined to the keratogenous zone of the wool follicle cortex.
      Expression of CAT activity in skin was correlated with diet-induced or seasonal
      changes in the rate of wool growth. This keratin promoter appears useful for
      overexpressing factors in the wool follicle that might influence wool production
      or properties.

PMID- 9636321
TI  - Improved wool production in transgenic sheep expressing insulin-like growth
      factor 1.
AB  - Transgenic sheep were produced by pronuclear microinjection with a mouse ultra
      high-sulfur keratin promoter linked to an ovine insulin-like growth factor 1
      (IGF1) cDNA. Five transgenic lambs resulted from the microinjection of 591
      embryos; one male and one female showed IGF1 expression in the skin. A progeny
      test of the ram was carried out by matings to 43 non-transgenic ewes. Of 85 lambs
      born, 43 (50.6%) were transgenic. At yearling shearing (approximately 14 months
      of age), clean fleece weight was on average 6.2% greater in transgenic animals
      than in their non-transgenic half-sibs, with a greater effect in males (9.2%)
      than females (3.4%). Transgenics showed a small but significant increase in bulk,
      but male transgenics had a lower staple strength than female transgenics and non
      transgenics which did not differ significantly. There were no significant
      differences in fiber diameter, medullation, and hogget body weight. To our
      knowledge this is the first reported improvement in a production trait by genetic
      engineering of a farm animal without adverse effects on health or reproduction.

PMID- 9636322
TI  - Restricting the dispersal of recombinant DNA: design of a contained biological
      catalyst.
AB  - To restrict horizontal gene spread and, thus, create organisms whose behavior in
      the field is more predictable, we have combined a mini-Tn5 cloning system that
      allows stable insertion of foreign genes into the chromosomes of a variety of
      Gram-negative bacteria with a gene-containment circuit based on the universal
      lethal-function colicin E3. Use of the system is exemplified by the construction
      of a micro-organism designed to degrade polychlorinated biphenyls, important
      environmental pollutants. The relevant genotype of the microorganism is subject
      to a stringent gene-containment mechanism that provides neither an advantage nor
      a disadvantage to the host cell for survival, but decreases frequencies of
      productive chromosomal transfer frequencies by at least four orders of magnitude.

PMID- 9636323
TI  - High level secretion of a humanized bispecific diabody from Escherichia coli.
AB  - Clinical development of bispecific antibodies (BsAb) has been effectively stymied
      by the lack of efficient production methods. We therefore attempted to produce a
      humanized BsAb fragment using an expression system that has proved very
      successful for secretion of monospecific Ab fragments from E. coli. An anti
      p185HER2/anti-CD3 BsF(ab')2 was first recast into the diabody format and then
      periplasmically secreted from E. coli grown to high cell density in a fermentor.
      The diabody was recovered in very high yield (up to 935 mg/l) after protein A
      purification and predominantly (> or = 80%) as a dimer as judged by size
      exclusion chromatography. Diabody dimers were found to be mainly functional
      heterodimers (approximately 75%) by titration with p185HER2 extracellular domain.
      The diabody binds p185HER2 extracellular domain and human T lymphocytes with
      affinities close to those of the parent BsF(ab')2. Furthermore, the diabody is
      capable of simultaneous binding to tumor cells overexpressing p185HER2 and CD3 on
      T cells as shown by cellular rosetting. The diabody is equally potent as the
      parent BsF(ab')2 in retargeting IL-2 activated T-enriched peripheral blood
      lymphocytes to lyse tumor cells overexpressing p185HER2.

PMID- 9636324
TI  - Development of new cloning vectors for the production of immunogenic outer
      membrane fusion proteins in Escherichia coli.
AB  - The Pseudomonas aeruginosa lipoprotein gene (oprI) was modified by cloning an in
      frame polylinker in both orientations at the end of oprI. The resulting plasmids
      pVUB1 and pVUB2 allow high lipoprotein production in E. coli after IPTG
      induction. The modified lipoproteins are present in the outer membrane and
      surface-exposed. Outer membrane-bound fusion proteins of different sizes were
      produced and used to generate antibodies without use of adjuvant. An 87 bp DNA
      fragment from the vp72 capsid protein gene of African Swine Fever virus (ASFV)
      and the entire Leishmania major glycoprotein gp63 gene were expressed in this
      system. Finally, a fusion lipoprotein containing a 16 amino acid epitope from the
      pre-S2b region of Hepatitis B virus (HBV) was presented by an antigen-presenting
      cell line to a T-cell hybridoma while the corresponding cross-linked S2b peptide
      was not. The results suggest that OprI-based fusion proteins can be used to
      generate both humoral and cellular immune responses.

PMID- 9636325
TI  - Thoughts on the prevention of neonatal group B streptococcal infection.

PMID- 9636326
TI  - Drug-induced disorders.

PMID- 9636327
TI  - Bacterial vaginosis: what's in a name?

PMID- 9636328
TI  - Accidental coin swallowing and sublingual nitroglycerin.

PMID- 9636329
TI  - Screening for prostate cancer.

PMID- 9636330
TI  - Air bag deployment and hearing loss.

PMID- 9636331
TI  - Novel treatment for leg ulcers.

PMID- 9636332
TI  - Diagnostic evaluation of urinary incontinence in geriatric patients.
AB  - In most cases, the evaluation of urinary incontinence requires only a history, a
      physical examination, urinalysis and measurement of postvoid residual urine
      volume. The initial purposes of the evaluation are to identify conditions
      requiring referral or specialized work-up and to detect and treat reversible
      causes that may be present. If the patient does not appear to require referral
      and a reversible cause is not identified, the next step is to categorize the
      patient's symptoms as typical of either urge or stress incontinence and treat the
      patient accordingly. If treatment fails or a presumptive diagnosis of urge or
      stress incontinence cannot be reached, the final step would be to perform more
      sophisticated tests or refer the patient for testing to define the cause and
      determine the best treatment.

PMID- 9636333
TI  - Eyelid disorders: diagnosis and management.
AB  - Eyelid problems range from benign, self-resolving processes to malignant,
      possibly metastatic, tumors. Inflammation, infection, benign and malignant
      tumors, and structural problems such as ectropion, entropion and blepharoptosis
      may occur. Fortunately, most eyelid disorders are not vision-threatening or life
      threatening; however, many cause irritative symptoms such as burning, foreign
      body sensation or pain. Blepharitis, or eyelid inflammation, one of the most
      common problems, is characterized by erythematous eyelids with accumulation of
      debris along the eyelid margin. Malignant eyelid tumors may be associated with
      lash loss and erosion of normal eyelid structures. Recognition and diagnosis of
      these problems are crucial to their proper management. Warm compresses and
      antibiotics suffice for many conditions, while excision, cryotherapy or laser
      treatment are required for some.

PMID- 9636334
TI  - The Charcot foot in diabetes: six key points.
AB  - The Charcot foot commonly goes unrecognized, particularly in the acute phase,
      until severe complications occur. Early recognition and diagnosis, immediate
      immobilization and a lifelong program of preventive care can minimize the
      morbidity associated with this potentially devastating complication of diabetic
      neuropathy. If unrecognized or improperly managed, the Charcot foot can have
      disastrous consequences, including amputation. The acute Charcot foot is usually
      painless and may mimic cellulitis or deep venous thrombosis. Although the initial
      radiograph may be normal, making diagnosis difficult, immediate detection and
      immobilization of the foot are essential in the management of the Charcot foot. A
      lifelong program of patient education, protective footwear and routine foot care
      is required to prevent complications such as foot ulceration.

PMID- 9636335
TI  - Prevention of neonatal group B streptococcal infection.
AB  - Neonatal group B streptococcal infection is the primary cause of neonatal
      morbidity related to infection. It can often be prevented by identifying and
      treating pregnant women who carry group B streptococci or who are at highest risk
      of transmitting the bacteria to newborns. Increasing evidence and expert opinion
      support intrapartum treatment of women at relatively high risk of delivering an
      infant with group B streptococcal infection. Such women can be identified through
      the use of an anogenital culture for group B streptococci obtained at 35 to 37
      weeks of gestation and by the presence of at least one of many risk factors
      associated with neonatal infection. These risk factors include preterm labor or
      rupture of the membranes at less than 37 weeks of gestation, previous delivery of
      an infant with invasive group B streptococcal disease, group B streptococcal
      bacteriuria during the present pregnancy, maternal intrapartum fever of 38
      degrees C (100.4 degrees F) or higher and rupture of the fetal membranes for 18
      hours or more. The recommended agent for intrapartum chemoprophylaxis is
      intravenous penicillin G; clindamycin is used in penicillin-allergic women. The
      use of risk markers alone to guide the administration of intrapartum antibiotics
      is much more cost-effective than other preventive strategies, but it exposes more
      women and infants to antibiotic-associated risks. Management of the infants of
      treated mothers is empiric and is currently guided by expert opinion.

PMID- 9636336
TI  - Current guidelines for antibiotic prophylaxis of surgical wounds.
AB  - Appropriately administered antibiotic prophylaxis reduces the incidence of
      surgical wound infection. Prophylaxis is uniformly recommended for all clean
      contaminated, contaminated and dirty procedures. It is considered optional for
      most clean procedures, although it may be indicated for certain patients and
      clean procedures that fulfill specific risk criteria. Timing of antibiotic
      administration is critical to efficacy. The first dose should always be given
      before the procedure, preferably within 30 minutes before incision.
      Readministration at one to two half-lives of the antibiotic is recommended for
      the duration of the procedure. In general, postoperative administration is not
      recommended. Antibiotic selection is influenced by the organism most commonly
      causing wound infection in the specific procedure and by the relative costs of
      available agents. In certain gastrointestinal procedures, oral and intravenous
      administration of agents with activity against gram-negative and anaerobic
      bacteria is warranted, as well as mechanical preparation of the bowel. Cefazolin
      provides adequate coverage for most other types of procedures.

PMID- 9636337
TI  - Assessment and treatment of bulimia nervosa.
AB  - Bulimia nervosa is characterized by binge eating and inappropriate compensatory
      behaviors, such as vomiting, fasting, excessive exercise and the misuse of
      diuretics, laxatives or enemas. Although the etiology of this disorder is
      unknown, genetic and neurochemical factors have been implicated. Bulimia nervosa
      is 10 times more common in females than in males and affects up to 3 percent of
      young women. The condition usually becomes symptomatic between the ages of 13 and
      20 years, and it has a chronic, sometimes episodic course. The long-term outcome
      has not been clarified. Other psychiatric conditions, including substance abuse,
      are frequently associated with bulimia nervosa and may compromise its diagnosis
      and treatment. Serious medical complications of bulimia nervosa are uncommon, but
      patients may suffer from dental erosion, swollen salivary glands, oral and hand
      trauma, gastrointestinal irritation and electrolyte imbalances (especially of
      potassium, calcium, sodium and hydrogen chloride). Treatment strategies are based
      on medication, psychotherapy or a combination of these modalities.

PMID- 9636338
TI  - Treatment of systemic lupus erythematosus: an update.
AB  - Systemic lupus erythematosus predominantly affects women and is more common in
      blacks. Although survival rates have improved, over one half of patients with
      systemic lupus erythematosus have permanent damage in one or more organ systems.
      Arthritis and cutaneous manifestations are most common, but renal, hematologic
      and neurologic manifestations contribute largely to morbidity and mortality.
      Treatment approaches emphasize using a combination of drugs to minimize chronic
      exposure to corticosteroids.

PMID- 9636339
TI  - Sudden death in young athletes: screening for the needle in a haystack.
AB  - Nontraumatic sudden death in young athletes is always disturbing, as apparently
      invincible athletes, become, without warning, victims of silent heart disease.
      Despite public perception to the contrary, sudden death in young athletes is
      exceedingly rare. It most commonly occurs in male athletes, who have estimated
      death rates nearly fivefold greater than the rates of female athletes. Congenital
      cardiovascular disease is the leading cause of non-traumatic sudden athletic
      death, with hypertrophic cardiomyopathy being the most common cause. Screening
      athletes for disorders capable of provoking sudden death is a challenge because
      of the low prevalence of disease, and the cost and limitations of available
      screening tests. Current recommendations for cardiovascular screening call for a
      careful history and physical examination performed by a knowledgeable health care
      provider. Specialized testing is recommended only in cases that warrant further
      evaluation.

PMID- 9636340
TI  - Evaluating hoarseness: keeping your patient's voice healthy.
AB  - Hoarseness is the term often used by patients to describe changes in their voice
      quality. The causes of hoarseness are determined after obtaining a detailed
      medical history of the circumstances preceding the onset of hoarseness and
      performing a thorough physical examination. The latter may include visualization
      of the vocal cords, possibly using indirect laryngoscopy, flexible
      nasolaryngoscopy or strobovideolaryngoscopy. In the absence of an upper
      respiratory tract infection, any patient with hoarseness persisting for more than
      two weeks requires a complete evaluation. When the patient has a history of
      tobacco use, cancer of the head and neck must be considered and ruled out. Voice
      abuse is one of the most common causes of hoarseness and can lead to other vocal
      pathologies such as vocal nodules. Good vocal hygiene can prevent and treat some
      pathologies, and voice therapy is a cornerstone of management in some cases of
      hoarseness.

PMID- 9636341
TI  - Combination antiretroviral therapy for HIV infection.
AB  - The primary goal of antiretroviral therapy for human immunodeficiency virus (HIV)
      infection is suppression of viral replication. Evidence indicates that the
      optimal way to achieve this goal is by initiating combination therapy with two or
      more antiretroviral agents. The agents now licensed in the United States for use
      in combination therapy include five nucleoside analog reverse transcriptase
      inhibitors (zidovudine, didanosine, zalcitabine, stavudine and lamivudine), two
      nonnucleoside reverse transcriptase inhibitors (delavirdine and nevirapine) and
      four protease inhibitors (saquinavir, ritonavir, indinavir and nelfinavir).
      Current recommendations suggest that antiretroviral therapy be considered in any
      patient with a viral load higher than 5,000 to 20,000 copies per mL, regardless
      of the CD4+ count. Selection of the combination regimen must take into account
      the patient's prior history of antiretroviral use, the side effects of these
      agents and drug-drug interactions that occur among these agents and with other
      drugs as well. Because of the potential for viral resistance, nonnucleoside
      reverse transcriptase inhibitors and protease inhibitors should only be used in
      combination therapy. Antiretroviral agents are rapidly being developed and
      approved, so physicians must make increasingly complex treatment decisions about
      medications with which they may be unfamiliar.

PMID- 9636342
TI  - Photo quiz. Flowering dermatosis.

PMID- 9636343
TI  - Significant FDA approvals in 1997.

PMID- 9636344
TI  - American Heart Association releases scientific statement on cardiovascular
      disease in women.

PMID- 9636345
TI  - AAP issues recommendations for the use of soy protein-based formulas in infant
      feeding.

PMID- 9636346
TI  - The value of measuring health care quality.

PMID- 9636347
TI  - Sudden tachycardia in an octagenarian.

PMID- 9636348
TI  - An inflamed elbow after an insect sting.
AB  - A 63-year-old man presented with fever and a painfully swollen right elbow and
      forearm. He had been stung by a yellow jacket two weeks earlier and had since
      found it increasingly difficult to bend his arm.

PMID- 9636349
TI  - Acute salicylate overdose.

PMID- 9636350
TI  - Dosage in ulcer study.

PMID- 9636351
TI  - Dizzy patients: the varieties of vertigo.
AB  - Some vertigo results from acute viral labyrinthitis or a cerebrovascular event;
      many cases are due to loose particulate matter within the semicircular canals. In
      the vast majority of patients, a careful history and appropriate clinical tests
      will suffice to identify the cause of the vertigo--and with benign paroxysmal
      positional vertigo, a simple clinical maneuver can also provide a cure.

PMID- 9636352
TI  - Evaluation and management of cervical polyps.

PMID- 9636353
TI  - Rash and shortness of breath in an elderly woman.

PMID- 9636354
TI  - Chronic hepatitis C: early intervention.
AB  - Chronic hepatitis C infection is the most common liver disease in the United
      States; it accounts for up to 12,000 deaths annually and is the most common
      referral for liver transplantation. Recognition of acute infection is desirable
      because treatment may prevent chronicity. Interferon remains the primary
      treatment, but new agents and combinations are being developed.

PMID- 9636355
TI  - Outpatient management of community-acquired pneumonia.
AB  - Recently published guidelines permit the decision to treat patients with
      community-acquired pneumonia on an outpatient basis to be made more confidently
      than in the past. In most cases, the risk of 30-day mortality can be evaluated
      without extensive laboratory testing. Antibiotic therapy with erythromycin or
      doxycycline is generally effective.

PMID- 9636356
TI  - Chronic myelogenous leukemia: extending the prospects for cure.
AB  - Advances in our understanding of the molecular defects underlying this leukemia
      have led to novel therapeutic approaches that have not only altered the natural
      history of the disease but also apparently effected cures in some patients. The
      next step may be to offer the possibility of a cure to all patients. Allogeneic
      bone marrow and T cell transplantation shows promise in this regard.

PMID- 9636357
TI  - Genetic stability of Sabin 1 strain of poliovirus: implications for quality
      control of oral poliovirus vaccine.
AB  - The Sabin vaccine strains of poliovirus, like all RNA viruses, exist as a
      quasispecies of genomic sequences whose composition can be altered during virus
      propagation. Since changes in vaccine virus during manufacture can enhance the
      neurovirulent potential of the vaccine, each monovalent lot of oral poliovirus
      vaccine (OPV) undergoes several tests to ensure consistency of manufacture,
      including the monkey neurovirulence test (MNVT). Recently, we proposed a new
      molecular approach for direct quantification of vaccine variants with
      neurovirulent potential as an alternative way to monitor consistency of OPV
      production. Analysis of the Sabin 1 genome allowed us to identify a limited
      number of specific loci that exhibit significant change during viral propagation
      in vitro and in vivo. Here we explore the possible roles of these changes and
      show that 7427-U-->C and 7441-G-->A alterations in the 3'-UTR of the Sabin 1
      virus do not increase monkey neurovirulence. These, as well as our previous
      results, suggest that only mutations in the 5'-UTR play a significant role in the
      limited increase in Sabin 1 monkey neurovirulence observed after extended
      propagation of the virus beyond the passage level used in vaccine production. Our
      studies with high-passage batches of the Sabin 1 strain confirmed the stability
      of this strain, which retains acceptable levels of monkey neurovirulence even
      after serial passages at elevated temperature. Compared to the MNVT, molecular
      analysis of the genetic composition of Sabin 1 poliovirus provides a more
      sensitive analytical approach to monitor consistency of vaccine production.

PMID- 9636358
TI  - Adenovirus VAI RNA antagonizes the RNA-editing activity of the ADAR adenosine
      deaminase.
AB  - The virus-associated VAI RNA of adenovirus is a small highly structured RNA that
      is required for the efficient translation of cellular and viral mRNAs at late
      times after infection. VAI RNA antagonizes the activation of the interferon
      inducible RNA-dependent protein kinase, PKR, an important regulator of
      translation. The RNA-specific adenosine deaminase, ADAR, is an interferon
      inducible RNA-editing enzyme that catalyzes the site-selective C-6 deamination of
      adenosine to inosine. ADAR possesses three copies of the highly conserved RNA
      binding motif (dsRBM) that are similar to the two copies found in PKR, the enzyme
      in which the prototype dsRBM motif was discovered. We have examined the effect of
      VAI RNA on ADAR function. VAI RNA impairs the activity of ADAR deaminase. This
      inhibition can be observed in extracts prepared from interferon-treated human
      cells and from monkey COS cells in which wild-type recombinant ADAR was
      expressed. Analysis of wild-type and mutant forms of VA RNA suggests that the
      central domain is important in the antagonism of ADAR activity. These results
      suggest that VAI RNA may modulate viral and cellular gene expression by
      modulating RNA editing as well as mRNA translation.

PMID- 9636359
TI  - Cyclophilin a modulates processing of human immunodeficiency virus type 1 p55Gag:
      mechanism for antiviral effects of cyclosporin A.
AB  - The molecular chaperone cyclophilin A (Cyp A) modulates human immunodeficiency
      virus type 1 (HIV-1) infectivity through its interactions with Gag structural
      proteins. The molecular mechanism for CypA in HIV-1 replication is not known. We
      studied chaperone effects on Gag precursor processing using cyclosporin A (CsA)
      to bind CypA and prevent its interaction with p55Gag. CsA treatment inhibited
      p55Gag processing in extracellular virus-like particles produced from COS cells.
      We confirmed the effect of CsA on Gag processing by examining virions produced
      from CEMx174 cells infected with HIV-1LAI. Particles accumulated in the presence
      of CsA displayed mostly immature virion morphology and lacked condensed capsids.
      CsA has a direct effect on HIV-1 Gag processing that implicates CypA as having an
      important role in the maturation of HIV-1 particles.

PMID- 9636360
TI  - Subcellular localization and some biochemical properties of the flavivirus Kunjin
      nonstructural proteins NS2A and NS4A.
AB  - In a previous study on the replication of Kunjin virus using immunoelectron
      microscopy (E. G. Westaway, J. M. Mackenzie, M. T. Kenney, M. K. Jones, and A. A.
      Khromykh, 1997, J. Virol. 71, 6650-6661), NS1 and NS3 were found associated with
      double-stranded RNA (dsRNA) within vesicle packets (VP) in infected Vero cells,
      suggesting that these induced membrane structures may be the cytoplasmic sites of
      RNA replication. NS2B and NS3 (comprising the virus-encoded protease) were
      colocalized within distinct paracrystalline (PC) or convoluted membranes (CM),
      also induced in the cytoplasm, suggesting that these membranes are the sites of
      proteolytic cleavage. In this study we found by immunofluorescence (IF) that the
      small hydrophobic nonstructural proteins NS2A and NS4A were located in discrete
      foci in the cytoplasm of infected cells at both 16 and 24 h postinfection,
      partially coincident with dsRNA foci. In cryosections of infected cells at 24 h,
      NS2A was located by immunogold labeling primarily within VP, associated with
      labeled dsRNA. NS2A fused to glutathione S-transferase (GST) bound strongly to
      the 3' untranslated region of Kunjin RNA and also to the proposed replicase
      components NS3 and NS5 in cell lysates. NS4A was localized by immunogold labeling
      within a majority of the virus-induced membranes, including VP, CM, and PC. GST
      NS4A bound weakly to the 3' untranslated region of Kunjin RNA but was bound to
      NS4A strongly and to most of the other viral nonstructural proteins, including
      NS3 and NS5. Taken together the results indicate that the flavivirus replication
      complex includes NS2A and NS4A in the VP in addition to the previously identified
      NS1 and NS3.

PMID- 9636361
TI  - Mouse adenovirus type-1 replication is restricted to vascular endothelium in the
      CNS of susceptible strains of mice.
AB  - Previous studies have shown that mouse adenovirus type-1 (MAV-1) caused a fatal
      hemorrhagic encephalitis in certain strains of mice. C57BI/6 mice exhibited 100%
      mortality when given as little 10(3) plaque-forming units (PFU) of MAV, in
      contrast to BALB/c mice which were resistant to as many as 10(6) PFU. Susceptible
      animals died with a flaccid paralysis on the 3rd or 4th day after inoculation.
      The brains and spinal cords of these animals displayed numerous petechial
      hemorrhages that were found in virtually all areas of the brain, but were more
      numerous in white matter. In this paper, immunohistochemistry and electron
      microscopy were used to identify the viral target of replication within the CNS
      of susceptible mice. These studies showed that the CNS vascular endothelial cell
      was the primary site of viral replication within the CNS of mice infected with
      MAV-1. Characterization of cytokine mRNA levels and disease course in
      immunodeficient mice revealed that the host immune response played little, if
      any, role in the pathogenesis of MAV-1 disease in susceptible mice and was not
      responsible for the resistance of BALB/c mice. These results support the
      conclusion that disease course and outcome in susceptible and resistant strains
      of mice were determined primarily by the ability of the virus to replicate within
      the CNS vascular endothelium.

PMID- 9636362
TI  - The predominant elF4G-specific cleavage activity in poliovirus-infected HeLa
      cells is distinct from 2A protease.
AB  - Human enteroviruses and rhinoviruses rapidly and selectively abolish translation
      from cellular mRNA upon infection of susceptible cells. Expression of the
      poliovirus 2A protease (PV 2Apro) is sufficient to cause host translation shutoff
      through cleavage of elF4G (formerly p220, elF4 gamma) either directly or
      indirectly through activation of a cellular factor. Evidence exists for both
      direct and indirect cleavage mechanisms; however, factors presumed to participate
      in an indirect mechanism have not yet been purified or defined. Here we show that
      the dominant elF4G cleavage activity in lysates from infected HeLa cells was
      separable from PV 2Apro by size exclusion chromatography. 2Apro separated into
      two peak fractions which contained activity which cleaved a peptide substrate
      derived from the poliovirus polyprotein. These peak 2Apro fractions did not
      cleave elF4G or an elF4G-derived peptide, as expected, due to the poor efficiency
      of direct cleavage reactions. Conversely, fractions which contained peak elF4G
      cleavage activity and only trace amounts of 2Apro efficiently cleaved a peptide
      substrate derived from the previously mapped elF4G cleavage site and also cleaved
      a peptide derived from the poliovirus 1D2A region. The dominant elF4G cleavage
      activity was highly purified through four chromatography steps and found to be
      devoid of all traces of 2Apro or its precursors. Quantitation of 2Apro from
      lysates of infected cells showed that during infections in HeLa cells, 2Apro does
      not reach molar excess over elF4G, as previously shown to be required for direct
      elF4G cleavage in vitro. Further, infection of HeLa cells in the presence of 2 mM
      guanidine-HCl, a potent inhibitor of viral RNA replication, suppressed
      accumulation of 2Apro and its precursor 2ABC below detectable levels but was
      unable to delay the onset of elF4G proteolysis in vivo. The elF4G cleavage
      activity was still easily detectable in in vitro assays using fractions from
      guanidine-treated cells. Thus, the data suggest that poliovirus utilizes two
      catalytic activities to ensure rapid cleavage of elF4G in vivo. Although it was
      not directly measurable here, 2Apro likely does cleave a portion of elF4G in
      cells. However, the data suggest that a cellular factor which can be activated by
      small quantities of 2Apro constitutes the bulk of the elF4G-specific cleavage
      activity in infected cells and is responsible for the rapid and efficient elF4G
      cleavage activity observed in vivo.

PMID- 9636363
TI  - Direct cleavage of elF4G by poliovirus 2A protease is inefficient in vitro.
AB  - Previously, the purified recombinant 2A proteases (2Apro) of coxsackievirus B4
      (CVB4) and human rhinovirus type 2 (HRV2) were shown to cleave synthetic peptides
      derived from human or rabbit elF4G as well as elF4G protein purified from rabbit
      reticulocytes. These results were in contrast to previous evidence which
      supported the view that elF4G cleavage activity in poliovirus-infected HeLa cells
      required a cellular factor(s) activated by poliovirus (PV) 2Apro. In the present
      study, recombinant PV 2Apro was shown to cleave either rabbit or human elF4G or
      their derived peptides in direct cleavage reactions, but cleaved the 4G-derived
      peptides with 100-fold lower efficiency than with a peptide derived from the
      poliovirus polyprotein. In these experiments, up to 25-fold molar excess of 2Apro
      over elF4G protein was required to cause greater than 50% cleavage. CVB4 2Apro
      was also tested in peptide cleavage assays under the same conditions as PV 2Apro
      and was found to cleave all elF4G substrates with efficiencies similar to PV
      2Apro. Finally, cleavage reactions utilizing recombinant elF4G containing a G486E
      substitution at the cleavage site for CVB4 and HRV2 proteases resulted in
      drastically reduced cleavage by PV 2Apro, similar to the reduction previously
      seen with HRV2 and CVB4 2Apro, confirming that all three viral 2A proteases
      recognize the same cleavage site on elF4G. These data show that PV 2Apro can
      directly cleave elF4G in vitro with efficiencies similar to those of CVB 2Apro,
      but cleavage efficiency of elF4G is approximately 1000-fold lower than cleavage
      of a peptide derived from the authentic 2A cleavage site on the poliovirus
      polyprotein.

PMID- 9636364
TI  - Three active forms of aspartic proteinase from Mason-Pfizer monkey virus.
AB  - Mason-Pfizer monkey virus (M-PMV) proteinase, released by the autocatalytic
      cleavage of Gag-Pro and Gag-Pro-Pol polypeptide precursors, catalyzes the
      processing of viral precursors to yield the structural proteins and enzymes of
      the virion. In retroviruses, usually only one proteolytically active form of
      proteinase exists. Here, we describe an unusual feature of M-PMV, the existence
      of three active forms of a retroviral proteinase with molecular masses of 17, 13,
      and 12 kDa as determined by mass spectroscopy. These forms arise in vitro by self
      processing of a 26-kDa proteinase precursor. We have developed a process for
      isolation of each truncated product and demonstrate that all three forms display
      proteolytic activity. Amino acid analyses, as well as the determination of N- and
      C-terminal sequences, revealed that the N-termini of all three forms are
      identical, confirming that in vitro autoprocessing of the 17-kDa form occurs at
      the C-terminus to yield the truncated forms. The 17-kDa form and the newly
      described 13-kDa form of proteinase were identified in virions collected from the
      rhesus monkey CMMT cell line chronically infected with M-PMV, confirming that
      multiple forms exist in vivo.

PMID- 9636365
TI  - The cAMP-dependent protein kinase A and protein kinase C-beta pathways
      synergistically interact to activate HIV-1 transcription in latently infected
      cells of monocyte/macrophage lineage.
AB  - The HIV-1 long terminal repeat (LTR) responds to a variety of cellular signal
      transduction pathways. We demonstrate that the cAMP-dependent protein kinase A
      (PKA) and protein kinase C (PKC) signaling pathways synergize to increase HIV-1
      LTR-mediated transcription and viral replication in a latently infected
      promonocytic cell line (U1). The LTR-mediated synergy induced by cholera toxin
      (Ctx), a potent activator of the cAMP-dependent PKA pathway, and the PKC
      activator phorbol 12-myristate 13-acetate (PMA) was abrogated by a PKC-beta
      specific inhibitor (LY333531). In contrast, the LTR-mediated synergy induced by
      Ctx and TNF alpha was not affected by LY333531. The synergy induced by Ctx and
      TNF alpha was also abrogated by mutation of the cAMP-responsive downstream
      sequence elements (DSE) in the 5' untranslated leader region, whereas the DSE
      mutations did not affect the synergy induced by Ctx and PMA. These distinctions
      indicate that Ctx cooperates differently with TNF alpha and PMA to activate the
      HIV-1 LTR. Ctx and PMA synergistically activated AP-1- and NF-kappa B-dependent
      transcription, even though no cooperative binding of AP-1 or NF-kappa B was
      observed in gel shift assays. An extensive mutational analysis of the HIV-1 LTR
      that included the NF-kappa B and AP-1 binding sites revealed no distinct cis
      acting element or region within the HIV-1 LTR that was required for the
      transcriptional synergy. Ctx and PMA also synergistically interact to activate
      the HTLV-1 LTR. These results indicate that the transcriptional synergy elicited
      by Ctx and PMA targets multiple functional elements and promoters, requires a
      cooperative interaction between the PKA and PKC-beta pathways, and differs
      mechanistically from the transcriptional synergy induced by Ctx and TNF alpha.

PMID- 9636366
TI  - The role of IL-10 in mouse hepatitis virus-induced demyelinating
      encephalomyelitis.
AB  - Interleukin 10 (IL-10) is an important anti-inflammatory cytokine. To examine its
      role in virus-induced encephalomyelitis, IL-10-deficient (IL-10 -/-) mice were
      infected with a neurotropic strain of mouse hepatitis virus (JHMV). JHMV-infected
      IL-10 -/- mice, compared to IL-4 -/- and syngeneic C57BL/6 mice, exhibited
      increased morbidity and mortality. Virus was cleared from the CNS of all groups
      of mice with equal kinetics by day 9 postinfection and the lack of either IL-4 or
      IL-10 did not alter the distribution of viral antigen, suggesting a lack of
      correlation between viral replication and the increased clinical disease in IL-10
      -/- mice. In moribund IL-10 -/- mice, a moderate increase in mononuclear cell
      infiltration was correlated with increased expression of tumor necrosis factor
      alpha, interferon-gamma, and inducible nitric oxide synthase mRNAs. In the small
      percentage of IL-10 -/- mice that survived, no differences in either
      demyelination or inflammation were observed. Together, these results suggest that
      IL-10 is not required for viral clearance, and although it appears to be one of
      the mechanisms responsible for inhibiting the extent of inflammation in the CNS
      during acute JHMV infection, it has little role in the eventual resolution of CNS
      inflammatory responses.

PMID- 9636367
TI  - Characterization of a linear epitope in the nonstructural region 4 of hepatitis C
      virus with reactivity to seroconversion antibodies.
AB  - Mapping and possible diagnostic meaning of a highly conserved, linear NS4 epitope
      (NS4/3), located outside the C100-3 antigen within the carboxyl terminal
      proportion of the NS4 region, with major immunoreactivity with specimens of
      patients with HCV infection from various geographic origins is described.
      Transient, acute-phase IgM anti-HCV NS4/3 was detected coincidentally or earlier
      than active IgG anti-HCV NS4/3 response with four well-characterized
      seroconversion panels. GenBank alignment studies identified patch homologies
      between the NS4/3 sequence and a number of non-HCV proteins, which may explain
      part of the cross-reactivity of the NS4/3 epitope. Some of the "false positive
      reactivities" of the NS4/3 epitope with asymptomatic blood donors, not being
      confirmed with FDA-approved anti-HCV assays without the NS4/3 epitope, may be
      explained by recognition of very early seroconversion antibodies.

PMID- 9636368
TI  - DNA sequences outside the simian virus 40 early region cause downregulation of T
      antigen production in permissive simian cells.
AB  - Using a series of modified wtSV40 and early region SV40 DNAs we assayed the
      effect of viral late region sequences on T-antigen production by the SV40 early
      region. We found that SV40 late region (L-SV40) DNA sequences reduced T-antigen
      (T-Ag) production by the SV40 early region (E-SV40) when both viral regions were
      linked as they are in wtSV40 DNA. This was demonstrated by Western analysis which
      showed that E-SV40 DNA produced 10 times more T-Ag than wtSV40 DNA L-SV40, with
      its own promoter but unlinked to E-SV40 DNA, also greatly inhibited T-Ag
      production when it was contrasfected with E-SV40. Therefore, L-SV40 DNA inhibited
      T-Ag production by E-SV40 DNA when present in cis or in trans. We have shown that
      expression of the SV40 late transcription unit dominated that of the early (T-Ag
      gene) transcription unit because late region RNA accumulated to much higher
      levels than early viral RNA. However, in contrasfected cells L-SV40 DNA did not
      replicate to higher levels than E-SV40 DNA. We offer a model for control of T-Ag
      expression in which a relatively small amount of T-Ag activates late
      transcription at the expense of T-Ag gene transcription and that this represents
      a switch from early to late viral gene expression. We suggest that when
      activation of the late transcription unit occurs at the late promoter, expression
      of the T-Ag gene is greatly reduced. The L-SV40 promoter may inhibit T-Ag gene
      transcription by sequestering cellular factors required for early transcription,
      factors which may be present in limited amounts. We suggest further that
      activation of late transcription allows for the necessary production of large
      amounts of capsomeres and virions and downregulation of early transcription
      prevents the early region from interfering with capsid synthesis. We tested the
      model using a construct with a wild-type T-Ag gene but with mutations in the SV40
      major late promoter which prevent the promoter from being bound by cellular
      repressors of late transcription. We found that this construct, which
      overproduces late SV40 RNA, was defective for T-Ag production. This indicates
      that activation of the late promoter results in repression of T-Ag gene
      expression.

PMID- 9636369
TI  - Characterization of the two overlapping papain-like proteinase domains encoded in
      gene 1 of the coronavirus infectious bronchitis virus and determination of the C
      terminal cleavage site of an 87-kDa protein.
AB  - In a previous report, we showed that proteolytic processing of an 87-kDa mature
      viral protein from the coronavirus infectious bronchitis virus (IBV) 1a and 1a/1b
      polyproteins was mediated by two putative overlapping papain-like proteinase
      domains (PLPDs) encoded within the region from nucleotides 4243 to 5553 of ORF 1a
      (Liu et al., 1995). In this study, we demonstrate that only the first domain,
      PLPD-1, is responsible for this cleavage, as deletion of the second domain did
      not affect the formation of the 87-kDa protein. Site-directed mutagenesis studies
      further showed that a previously predicted nucleophilic cysteine residue
      (Cys1274) and a histidine residue (His1437) were essential for the proteinase
      activity, indicating that they may be important components of the catalytic
      center of the proteinase. Meanwhile, expression of a series of deletion mutants
      revealed that the 87-kDa protein was encoded by the 5'-most 2.6 kb of ORF 1a.
      Deletion and amino acid substitution mutation studies demonstrated that the
      Gly673-Gly674 dipeptide bond was most likely the cleavage site responsible for
      releasing the C-terminus of the 87-kDa protein from the 1a and 1a/1b
      polyproteins.

PMID- 9636370
TI  - Characterization of the interactions among vaccinia virus transcription factors
      G2R, A18R, and H5R.
AB  - Prior genetic analysis suggests that there may exist an interaction between the
      products of the vaccinia virus genes A18R, a putative negative transcription
      elongation factor, and G2R, a putative positive transcription elongation factor.
      In addition, affinity purification of polyhistidine-tagged G2R protein
      overexpressed in vaccinia virus-infected cells, reported here, results in
      copurification of the vaccinia H5R protein, previously characterized as a late
      viral transcription factor. We have therefore used several methods to screen
      further for interactions among the G2R, A18R, and H5R proteins. Methods include
      copurification or co-immunoprecipitation of proteins overexpressed during
      vaccinia virus infection, activation of the gal 4 promoter by gal 4 fusions in
      the yeast two-hybrid system, and co-immunoprecipitation of proteins synthesized
      in vitro in a rabbit reticulocyte lysate. The results reveal interactions which
      include all possible pairwise combinations of the three proteins G2R, A18R, and
      H5R; however, not all possible permutations of the interactions are observed and
      the interactions are not observed in all environments tested. The results suggest
      that the vaccinia virus proteins G2R, A18R, and H5R interact as part of a higher
      order transcription complex.

PMID- 9636371
TI  - HHR23A, the human homologue of the yeast repair protein RAD23, interacts
      specifically with Vpr protein and prevents cell cycle arrest but not the
      transcriptional effects of Vpr.
AB  - Yeast two-hybrid selection of proteins interacting with human immunodeficiency
      virus type 1 Vpr identified HHR23A, a human homologue of the yeast DNA repair
      protein RAD23, as a specific interactor. A small 57-amino-acid C-terminal portion
      of HHR23A was sufficient for Vpr interaction. When introduced into human cells by
      transfection, full-length HHR23A or its C-terminal fragments were able to
      alleviate Vpr-induced cell cycle arrest, suggesting that HHR23A may participate
      in the pathway leading to G2 arrest by Vpr. We have also examined the effects of
      HHR23 on the recently identified transcription coactivator function of Vpr. The
      two Vpr functions are independent, since we have identified mutants lacking
      either the cell cycle arrest or the coactivator function. Our analysis showed
      that excess of HHR23A does not affect the coactivator function of Vpr, while it
      affects the cell cycle arresting function. Therefore, a simple sequestering model
      for Vpr in the presence of excess HHR23A is not supported. We propose that the
      interaction of HHR23A with Vpr may affect specifically pathways leading to cell
      cycle regulation.

PMID- 9636372
TI  - High-temperature inducible cell-free transcription and replication of double
      stranded RNAs within the parasitic protozoan Cryptosporidium parvum.
AB  - Sporozoites of the protozoan parasite, Cryptosporidium parvum, were found to
      contain free, full-size plus strands transcribed from two extrachromosomal,
      cytoplasmic, virus-like double-stranded RNAs (dsRNAs). Cell-free transcription
      and replication of both dsRNAs were observed in crude sporozoite lysates. RNA
      polymerase activity was found to be dependent upon addition of Mg2+ or Mn2+, as
      well as the four ribonucleoside triphosphates, and was insensitive to inhibitors
      of cellular DNA-dependent RNA polymerase. Semiconservative transcription of the
      dsRNAs (plus strand synthesis) was observed at a wide range of temperatures, with
      an optimum of 50 degrees C. In contrast, replication (minus strand synthesis) was
      detected only at 50 and 60 degrees C.

PMID- 9636373
TI  - Differential association of uracil DNA glycosylase with SIVSM Vpr and Vpx
      proteins.
AB  - The HIV-1 Vpr protein is a virion-associated protein which has been shown to
      facilitate infection of nondividing macrophages and additionally to alter cell
      cycle and proliferation status of the infected host cell. HIV-1 Vpr also was
      recently shown to associate with the DNA repair enzyme uracil DNA glycosylase
      (UDG). This association with a DNA repair enzyme is intriguing given that
      nonprimate lentiviruses encode a dUTPase, which, like UDG, minimizes the
      misincorporation of uracil into DNA and is important for virus replication in
      primary nondividing macrophages but not in dividing cells. This raises the
      possibility that the dependence upon Vpr for infection of nondividing macrophages
      may relate to its ability to interact with UDG. Members of the HIV-2/SIVSM group
      encode, in addition to Vpr, a related protein called Vpx. We previously
      demonstrated (Fletcher et al., 1996) that Vpx of HIV-2/SIVSM is necessary and
      sufficient for infection of primary macaque macrophages, while Vpr is not
      required for macrophage infection but governs cell cycle arrest. Here, we extend
      on these observations by demonstrating that Vpr, but not Vpx of HIV-2/SIVSM,
      associates with UDG, which suggests that Vpx facilitates infection of macrophages
      by a UDG-independent mechanism.

PMID- 9636374
TI  - Identification of two replicons in phage-plasmid P4.
AB  - DNA replication of phage-plasmid P4 proceeds bidirectionally from the ori1 site
      (previously named ori), but requires a second cis-acting region, crr. Replication
      depends on the product of the P4 alpha gene, a protein with primase and helicase
      activity, that binds both ori1 and crr. A negative regulator of P4 DNA
      replication, the Cnr protein, is required for copy number control of plasmid P4.
      Using a plasmid complementation test for replication, we found that two
      replicons, both dependent on the alpha gene product, coexist in P4. The first
      replicon is made by the cnr and alpha genes and the ori1 and crr sites. The
      second is limited to the alpha and crr region. Thus, in the absence of the ori1
      region, replication can initiate at a different site. By deletion mapping, a cis
      acting region, ori2, essential for replication of the alpha-crr replicon was
      mapped within a 270-bp fragment in the first half of the alpha gene. The ori2
      site was found to be dispensable in a replicon that contains ori1. A construct
      that besides crr and alpha carries also the cnr gene was unable to replicate,
      suggesting that Cnr not only controls replication from ori1, but also silences
      ori2.

PMID- 9636375
TI  - A surface immunodeterminant of human papillomavirus type 16 minor capsid protein
      L2.
AB  - We used human papillomavirus type 16 (HPV-16) particles composed of capsid
      proteins L1 and L2 (L1/L2 capsids) as an antigen to produce mouse monoclonal
      antibodies (MAbs). Of 18 MAbs recognizing surface epitopes of L1/L2 capsids, 1
      was an anti-L1 MAb and 17 were anti-L2 MAbs. Seven of 11 anti-L2 MAbs recognizing
      linear epitopes wer found to bind to a synthetic peptide with an HPV-16 L2
      sequence of amino acids (aa) 69-81, which is within a highly conserved region
      among different HPVs. The synthetic peptide reacted with the human sera that had
      been shown to be positive for an antibody against HPV-16, -18, -58, or -6b
      capsids composed of L1 alone. The data suggest that the HPV-16 L2 region of aa 69
      81 contains a type-common immunodeterminant exposed on the surface of HPV
      virions.

PMID- 9636376
TI  - Vaccinia virus nucleoside triphosphate phosphohydrolase I is an essential viral
      early gene transcription termination factor.
AB  - Deng and Shuman (J. Biol Chem. 271, 29386 (1996)) reported that an ATPase
      different from the known viral termination factor, VTF, is required for vaccinia
      virus early gene transcription termination. Properties of this ATPase were
      similar to those of a known vaccinia virus enzyme, nucleoside triphosphate
      phosphohydrolase I (NPH I) the product of gene D11L. Transcription-competent cell
      free extracts were prepared from A549 cells infected with wild-type or mutant
      vaccinia virus harboring ts mutations in gene D11L. These extracts were employed
      to investigate the role of NPH I in early gene transcription termination.
      Extracts prepared under nonpermissive conditions from both wild-type virus and ts
      mutant virus-infected cells exhibited high levels of early and intermediate gene
      transcription activity but were incapable of supporting late gene transcription.
      ts mutant extract lacked signal-dependent early gene transcription termination
      activity, which was restored by the addition of either free NPH I or a GST-NPH I
      fusion protein. A comparison of the NPH I amino acid sequence to the protein
      databases revealed the presence of a set of sequences characteristic of nucleic
      acid helicase superfamily II members. A series of site-specific mutations in the
      helicase motifs and N-terminal and C-terminal deletion mutations were expressed
      as GST fusion proteins and their activities assessed. Of the mutations in
      helicase motifs I to VI, alteration of all but motif III reduced the ATPase
      activity. Removal of as few as 24 amino acids from the N-terminal end eliminated
      ATPase activity, while deletion of 68 C-terminal amino acids exhibited only a
      modest decrease in ATP hydrolysis. Larger C-terminal deletions eliminated ATPase
      activity. Each deletion mutation, and site-specific mutations other than the
      motif III mutation, failed to support transcription termination in vitro.
      Mutations in motifs I, II, V, and VI inhibit wild-type NPH I transcription
      termination activity. However, deletion of up to 68 amino acids from the C
      terminal end eliminates this inhibitory property. This observation is
      particularly interesting since these C-terminal deletions retain both ATPase
      activity and single-stranded DNA binding activity. Their failure to inhibit
      transcription termination suggests that these C-terminal deletion mutations
      eliminate a site required for a function other than from DNA binding or ATP
      hydrolysis.

PMID- 9636378
TI  - Combined blockade of CD28/B7 and CD40/CD40L costimulatory pathways prevents the
      onset of chronic rejection.

PMID- 9636377
TI  - Blockade of alpha 4 beta 1-integrin-fibronectin adhesive interactions prevents
      chronic allograft rejection in sensitized recipients.

PMID- 9636379
TI  - Prolonged survival of recipient rats with Fas-ligand-transfected liver allografts
      by using HVJ-liposome.

PMID- 9636380
TI  - TGF-beta: a link between immunosuppression, nephrotoxicity, and CsA.

PMID- 9636381
TI  - Accelerated arteriosclerosis in aortic grafts: a role for cytokines in
      progressive intimal lesion development.

PMID- 9636382
TI  - Effect of cyclosporine and Sirolimus on interleukin-15-driven proliferation of
      OKT3-preactivated human lymphocytes.

PMID- 9636383
TI  - Long-term treatment with CsA decreases INF-gamma mRNA and increases pre-pro-ET-1
      mRNA in rat kidneys.

PMID- 9636384
TI  - Is TGF-beta a profibrotic cytokine in human renal transplants?

PMID- 9636385
TI  - High local production of nitric oxide as a possible mechanism by which rapamycin
      prevents transplant arteriosclerosis.

PMID- 9636386
TI  - Activation of COL3A1 promoter activity by cyclosporine.

PMID- 9636387
TI  - Expression of collagen by renal fibroblasts treated with FK 506 in vitro.

PMID- 9636388
TI  - Differences in the mode of action of cyclosporine and FK 506.

PMID- 9636389
TI  - Effect of mycophenolate mofetil on atherosclerosis in a rabbit model: initial
      histologic and immunohistochemical analyses.

PMID- 9636390
TI  - Hyperacute skin allograft rejection in presensitized rats is abrogated by
      malononitrilamides.

PMID- 9636391
TI  - Inhibition of alloreactivity in the popliteal lymph node assay by
      malononitrilamides.

PMID- 9636392
TI  - In vitro efficacy of conjugates of anti-CD45 monoclonal antibodies with plant
      toxin A-chains.

PMID- 9636393
TI  - Effect of the lazaroid U-74389G on chemokine gene expression and apoptosis in
      renal ischemia-reperfusion injury.

PMID- 9636394
TI  - Malononitrilamides reduce IgM and IgG xenoantibodies and prolong skin xenograft
      survival in a mouse-to rat model.

PMID- 9636395
TI  - Immunosuppressive effect of the hydrophobic extract of a Chinese herb on rat lung
      allograft rejection.

PMID- 9636396
TI  - Effect of mycophenolate mofetil on the in vivo infiltration of lymphocytes in the
      rat remnant kidney.

PMID- 9636397
TI  - In vitro study of BCX-34: a new human T-lymphocyte-specific purine phosphorylase
      inhibitor.

PMID- 9636398
TI  - Comparison of the effect of FK 506 and alpha/beta-T-cell antibody R73 on
      transplant vascular sclerosis after heterotopic rat heart transplantation.

PMID- 9636399
TI  - Different effects of cyclosporine or tacrolimus on hepatocyte acute phase
      proteins.

PMID- 9636400
TI  - An investigation into the effects of cyclosporine and FK 506 on the progress of
      chronic rejection in the rat aortic model.

PMID- 9636401
TI  - HMG-CoA reductase inhibitors pravastatin and simvastatin inhibit human B
      lymphocyte activation.

PMID- 9636402
TI  - Oral delivery of low molecular weight heparin in rat cardiac allografts.

PMID- 9636403
TI  - Pravastatin and cyclosporine inhibit platelet-derived growth factor-stimulated
      vascular smooth muscle cell mitogenesis: an investigation of mechanisms.

PMID- 9636404
TI  - Liposomal tacrolimus: drug migration within blood compartments.

PMID- 9636405
TI  - T cells infiltrating coronary arteries of cardiac allografts with chronic
      rejection contain clonally expanded T lymphocytes.

PMID- 9636406
TI  - Early treatment of acute rejection prevents chronic rejection in a rat model of
      allogenic left lung transplantation.

PMID- 9636407
TI  - Downregulation of endothelin expression in allograft coronary arteries after gene
      therapy targeting Cdk2 kinase.

PMID- 9636408
TI  - Effect of low molecular weight heparin on suppression of chronic graft vascular
      disease in a rat cardiac allograft model.

PMID- 9636409
TI  - Effect of cyclosporine on chronic graft vascular disease in a rat cardiac
      isograft model.

PMID- 9636410
TI  - Effect of hemodynamics on graft rejection in the heterotopic heart
      transplantation model.

PMID- 9636411
TI  - Accelerated arteriosclerosis in aortic grafts: a role for activated complement
      and IgM antibody in early lesion development.

PMID- 9636412
TI  - An experimental model of ischemia-produced transplant arteriosclerosis.

PMID- 9636413
TI  - Cellular surface molecular and cytokine gene expression in rat heart allografts
      under optimal doses of cyclosporine and FK 506.

PMID- 9636414
TI  - Influence of initial antigen-independent events on acute allograft rejection:
      inhibition by a soluble P-selectin ligand and low-dose cyclosporine in
      combination.

PMID- 9636415
TI  - Development of a macromolecular prodrug of FK 506: III: In vivo disposition of FK
      506-dextran conjugate.

PMID- 9636416
TI  - Development of a macromolecular prodrug of FK 506: II: In vitro study for FK 506
      dextran conjugate.

PMID- 9636417
TI  - Combined effect of rapamycin and cyclosporine in the prevention of rat corneal
      allograft rejection.

PMID- 9636418
TI  - Rapamycin's effect on vasomotion in the rat.

PMID- 9636419
TI  - FK 506 and rapamycin in combination are not antagonistic but produce extended
      small bowel graft survival in the mouse.

PMID- 9636420
TI  - Donor-specific blood transfusion does not enhance the effect of FTY720 in rat
      cardiac allotransplantation.

PMID- 9636421
TI  - Prevention of experimentally induced autoimmune type I diabetes in rats by the
      new immunosuppressive reagent FTY720.

PMID- 9636422
TI  - An effect of FTY720 on acute rejection in canine renal transplantation.

PMID- 9636423
TI  - Comparative effects of malononitriloamide analogs of leflunomide on whole blood
      lymphocyte stimulation in humans, rhesus macaques, cats, dogs, and rats.

PMID- 9636424
TI  - Mycophenolate mofetil's effect on accelerated heart allograft rejection and
      rejection markers in the rat.

PMID- 9636425
TI  - Methylprednisolone in bilayer liposomes prolongs cardiac and renal allograft
      survival, inhibits macrophage activation, and selectively modifies antigen
      presentation and T-helper cell function in rat recipients.

PMID- 9636426
TI  - Tumor recurrence in liver grafts: two animal models.

PMID- 9636427
TI  - CD95L confers immune priviledge to liver grafts which are spontaneously accepted.

PMID- 9636428
TI  - Anti-human class I alpha 3 domain-specific monoclonal antibody induces programmed
      cell death in murine cells expressing human class I MHC transgenes.

PMID- 9636429
TI  - Blocking of costimulatory pathways using monoclonal antibodies as a new strategy
      to prevent transplant rejection in a non-human primate model.

PMID- 9636431
TI  - Intrathymic inoculation of donor bone marrow at the time of transplantation plus
      a short course of tacrolimus induce long-term acceptance to rat lung allografts.

PMID- 9636430
TI  - CD4-targeted therapy and CD28-B7 costimulatory blockage may independently induce
      tolerance in sensitized allograft recipients.

PMID- 9636432
TI  - Beneficial immunosuppressive effect of FTY720 combined with intrathymic injection
      of splenic cells on rat pancreaticoduodenal allograft.

PMID- 9636433
TI  - Inhibition of intestinal allograft rejection by an anti-CD8 monoclonal antibody
      is not mediated by depletion alone.

PMID- 9636434
TI  - Prevention of recurrence of autoimmune diabetes type I in rats following
      pancreaticoduodenal transplantation.

PMID- 9636435
TI  - Differential resistance of the cellular immune responses and immunoregulatory
      properties of human cadaveric donor bone marrow cells to immunosuppressive drugs
      commonly used in transplantation.

PMID- 9636436
TI  - Development of tolerance in a chronic rejection model.

PMID- 9636437
TI  - Prolonged rat cardiac allograft survival using adenoviral vector containing the
      CTLA4Ig gene.

PMID- 9636438
TI  - Construction of a single-chain antibody derived from 5H7, a monoclonal antibody
      specific for a death signaling domain of human class I major histocompatibility
      complex.

PMID- 9636440
TI  - Effects of immunosuppression and pretransplant splenectomy in newborn cardiac
      xenograft survival.

PMID- 9636439
TI  - Squirrel monkeys hyperacutely reject porcine musculocutaneous flaps despite a
      lack of naturally occurring xenoantibodies.

PMID- 9636441
TI  - Analysis of B cell subsets responsible for the production of anti-donor
      antibodies in hamster-to-rat xenorejection.

PMID- 9636442
TI  - A novel in vitro model for xenorejection and immune mechanisms using
      bioengineered living skin equivalents.
AB  - We hypothesized that an in vitro bioengineered skin (LSE) could be used for the
      study of xenogeneic inflammatory or immunosuppressive mechanisms. Murine
      fibroblasts (10(4)/mL) were mixed with type 1 rat-tail collagen to form a matrix
      (approximately 5 days) on which human keratinocytes (NHEK, 10(5)/75 microL) were
      seeded. The xeno-LSE was used as a rejection target organ in vitro. Rejection was
      achieved by the addition of human lymphocytes (10(6)/75 microL). At various
      intervals of growth, control LSEs without lymphocytes (CON) and rejecting LSEs
      with immunocytes (REJ) were analyzed. Slides were stained with hematoxylin &
      eosin and examined under light microscopy. REJ xenocomposite LSEs showed classic
      histologic signs of rejection. There was separation of the D-E junction with the
      presence of dyskeratotic and necrotic cells with a concomitant inflammatory
      infiltrate. The CON LSEs showed essentially normal dermis (collagen fibroblast
      matrix) and keratinocytes. A significant finding was the separation of the D-E
      junction in the absence of an inflammatory infiltrate. Previous studies have
      shown that human keratinocytes can be grown with human fibroblasts that are
      histologically similar to natural human skin. This discohesive nature of the
      murine fibroblasts and human keratinocytes may represent an important
      intercellular interaction associated with xeno-cellular interactions and is
      worthy of further study. Furthermore, the ability to grow xeno-composite tissues
      has profound implications in the face of organ donor shortages. They may
      represent an eventual in vitro replacement of skin and even solid organs.

PMID- 9636443
TI  - Genetic characteristics of anti-donor immunoglobulin G antibodies in the hamster
      to-rat model of xenotransplantation.

PMID- 9636444
TI  - Tacrolimus enhances the immunosuppressive effect of cyclophosphamide but not that
      of leflunomide or mycophenolate mofetil in a model of discordant liver
      xenotransplantation.

PMID- 9636445
TI  - Controversies in heart and lung transplantation immunosuppression: tacrolimus
      versus cyclosporine.

PMID- 9636446
TI  - Effects of tacrolimus and cyclosporine on the coronary microcirculation after
      heart transplantation: a prospective study with serial intracoronary flow
      measurements.

PMID- 9636447
TI  - Cytolytic induction therapy in heart and lung transplantation: the protagonist
      opinion.
AB  - From the studies analysed as well as based on our own experience, induction
      therapy mainly with polyclonal cytolytic agents represents a helpful tool in the
      individualised immunosuppressive approach, whereas monoclonal induction therapies
      have to be discussed carefully. Although transplantation is also feasible without
      cytolytic agents, certain patients at risk will further encourage the need for
      this valuable therapy also in the future, where new immunosuppressants are
      available. However, it is anticipated that the application should be conducted on
      an individual patient basis to achieve optimal individual benefit.

PMID- 9636448
TI  - Contribution of the inflammatory response to cardiac allograft rejection:
      histopathologic analysis of serial endomyocardial biopsies.

PMID- 9636449
TI  - Long-term outcome with the use of OKT3 induction therapy in heart transplant
      patients: a single-center experience.

PMID- 9636450
TI  - Use of intravenous immunoglobulin in sensitized LVAD recipients.

PMID- 9636451
TI  - Pharmacokinetics of tacrolimus (FK506) in primary orthotopic heart transplant
      patients.

PMID- 9636452
TI  - Clinical outcomes associated with conversion to tacrolimus-based
      immunosuppression in pediatric cardiac transplantation.

PMID- 9636453
TI  - Posttransplant lymphoproliferative disorders in cardiac transplant patients.

PMID- 9636454
TI  - Unusual course of T-cell lymphoproliferative disorder in a cardiac transplant
      patient.

PMID- 9636455
TI  - Survival of heart transplant recipients with cyclosporine-induced renal
      insufficiency.

PMID- 9636456
TI  - High incidence and clinical course of aggressive skin cancer in heart transplant
      patients: a single-center study.

PMID- 9636457
TI  - Effect of allopurinol on the metabolism of azathioprine in heart transplant
      patients.

PMID- 9636458
TI  - Does preexisting elevated pulmonary vascular resistance (transpulmonary gradient
      > 15 mm Hg or > 5 wood) predict early and long-term results after orthotopic
      heart transplantation?

PMID- 9636459
TI  - Rapid trabecular bone loss after cardiac transplantation using FK506 (tacrolimus)
      based immunosuppression.

PMID- 9636460
TI  - Medium-term outcome of tacrolimus immunosuppression following rejection or graft
      dysfunction in heart transplant patients.

PMID- 9636461
TI  - Evidence for a type 2 bias in the CD8+ T-cell response to Epstein-Barr virus
      following heart transplantation.

PMID- 9636462
TI  - Combined chronic administration of methotrexate and cyclosporine A following
      cardiac ongoing rejection.

PMID- 9636463
TI  - Natural history and the clinical importance of early and late grade 2 cellular
      rejection following cardiac transplantation.

PMID- 9636464
TI  - Effect of Sandimmune cyclosporine on renal blood flow and function in heart
      transplant recipients.

PMID- 9636465
TI  - Risks and benefits of withdrawing cyclosporine from the long-term
      immunosuppression regimen of heart and heart-lung transplant recipients.

PMID- 9636466
TI  - Clinical impact of Neoral in heart transplantation.

PMID- 9636467
TI  - Can anti-HLA antibody analyses postcardiac transplantation predict acute
      allograft rejection and survival?

PMID- 9636468
TI  - Neoral conversion in stable thoracic transplant patients leads to dose reduction.

PMID- 9636469
TI  - Changes in T-cell subsets after renal transplantation in nonimmunosuppressed
      baboons.

PMID- 9636470
TI  - Depressed expression of CD 28 antigen on lymphocytes in long-term kidney
      transplant patients.

PMID- 9636471
TI  - Immunoglobulin class switch of posttransplant panel reactive antibody and the
      impact on kidney allograft outcome.

PMID- 9636472
TI  - Novel concept for easy quantification of posttransplant immunocompetence.

PMID- 9636473
TI  - Predicting factors for long-term results of OKT3 therapy in steroid-resistant
      acute rejection following cadaveric renal transplantation.

PMID- 9636474
TI  - Late acute rejection is more prevalent among African-American renal allograft
      recipients and is frequently associated with allograft loss.

PMID- 9636475
TI  - Effect of antirejection therapy on HLA-DR antigens and ICAM-1 expression on
      parenchymal cells as monitored by fine needle aspiration biopsy.

PMID- 9636476
TI  - Primary therapy with OKT3 for biopsy-proven acute renal allograft rejection.

PMID- 9636477
TI  - Importance of degree of eosinophilia in inflammatory infiltrates within renal
      allografts in the response to immunosuppressive treatment.

PMID- 9636478
TI  - Limited sampling strategy for the determination of mycophenolic acid area under
      the curve in pediatric kidney recipients. German Study Group on MMF Therapy in
      Pediatric Renal Transplant Recipients.

PMID- 9636480
TI  - Selective CellCept therapy in high-risk renal transplant recipients.

PMID- 9636479
TI  - Therapeutic drug monitoring of mycophenolic acid: comparison of HPLC and
      immunoassay reveals new MPA metabolites.

PMID- 9636481
TI  - Conversion to mycophenolate mofetil for chronic progressive deterioration of
      renal allograft function: first clinical experiences in 44 patients.

PMID- 9636482
TI  - Relation of mycophenolic acid trough levels and adverse events in kidney
      allograft recipients.

PMID- 9636483
TI  - Use of mycophenolate mofetil in patients with chronic cyclosporine
      nephrotoxicity.

PMID- 9636484
TI  - Area under the curve of Neoral and chronic use of mycophenolate mofetil.

PMID- 9636485
TI  - Abbreviating area under the curves further: a practical approach to monitoring
      extended pharmacokinetics with Neoral.

PMID- 9636486
TI  - Randomized trial to evaluate the use of increasing the steroid dose during
      conversion from cyclosporine to azathioprine.

PMID- 9636487
TI  - Cyclosporine-related hemolytic-uremic syndrome in kidney graft recipients:
      clinical and histomorphologic evaluation.

PMID- 9636488
TI  - Is cyclosporine toxic to the transplanted kidney with acute tubular necrosis?

PMID- 9636489
TI  - Causes of long-term renal allograft failure: no chronic rejection at three years.

PMID- 9636490
TI  - Successful therapy of chronic renal allograft failure by enhanced
      immunosuppression.

PMID- 9636491
TI  - Role of acute rejection in chronic rejection.

PMID- 9636492
TI  - Effect of tacrolimus on the outcome of renal transplantation with donor-specific
      blood transfusion.

PMID- 9636493
TI  - FK 506 as primary immunosuppressive therapy in renal transplantation.

PMID- 9636494
TI  - Tacrolimus (FK 506) in kidney transplantation: three-year survival results of the
      US multicenter, randomized, comparative trial. FK 506 Kidney Transplant Study
      Group.

PMID- 9636495
TI  - Tacrolimus therapy for ABO-incompatible kidney transplantation.

PMID- 9636496
TI  - Primary low-dose tacrolimus immunosuppressive prophylaxis for high-risk kidney
      transplant recipients.

PMID- 9636497
TI  - Long-term results of living kidney transplantation under tacrolimus
      immunosuppression: a single-center experience.

PMID- 9636498
TI  - Long-term comparison of tacrolimus and cyclosporine-based immunosuppression in
      kidney recipients with grafts from non-heart-beating cadaver donor.

PMID- 9636499
TI  - Preoperative induction with tacrolimus does not have a detrimental effect on
      primary graft function in adult cadaveric renal transplantation.

PMID- 9636500
TI  - Use of tacrolimus as the primary immunosuppression after renal transplant in
      Native Americans and Hispanics.

PMID- 9636501
TI  - Tacrolimus therapy for refractory acute renal allograft rejection: a 4-year
      experience with an aggressive approach.

PMID- 9636502
TI  - Combining FK 506 and mycophenolate mofetil for the treatment of acute
      corticosteroid-resistant rejection following kidney transplantation: a new
      therapeutic concept.

PMID- 9636503
TI  - Tacrolimus rescue therapy in late rejection after renal transplantation: outcome
      after 18 months.

PMID- 9636504
TI  - Improvement of nephrotoxicity, hypertension, and lipid metabolism after
      conversion of kidney transplant recipients from cyclosporine to tacrolimus.

PMID- 9636505
TI  - Elective conversion of patients from cyclosporine to tacrolimus for
      hypertrichosis.

PMID- 9636506
TI  - Conversion from cyclosporine to tacrolimus in renal allograft recipients with
      chronic graft nephropathy: preliminary report.

PMID- 9636507
TI  - Conversion from Neoral (cyclosporine) to tacrolimus of kidney transplant
      recipients for gingival hyperplasia or hypertrichosis.

PMID- 9636508
TI  - Reversal of delayed hyperacute renal allograft rejection with a tacrolimus-based
      therapeutic regimen.

PMID- 9636509
TI  - Tacrolimus for steroid- and OKT3-resistant rejection in kidney recipients.

PMID- 9636510
TI  - Cyclosporine to tacrolimus: effect on hypertension and lipid profiles in renal
      allografts.

PMID- 9636511
TI  - Tacrolimus for rescue of refractory renal allograft rejection.

PMID- 9636512
TI  - Factors affecting the pharmacokinetics of tacrolimus in the first year after
      renal transplantation. European Tacrolimus Multicentre Renal Study Group.

PMID- 9636513
TI  - Influence of hepatitis C virus infection on FK 506 blood levels in renal
      transplant patients.

PMID- 9636514
TI  - Tacrolimus dosing requirements in diabetic and nondiabetic patients calculated
      from pretransplantation data.

PMID- 9636515
TI  - The effect of breakfast on the oral bioavailability of tacrolimus in diabetic and
      nondiabetic patients before transplantation.

PMID- 9636516
TI  - Effect of breakfast on the oral bioavailability of tacrolimus and changes in
      pharmacokinetics at different times posttransplant in renal transplant
      recipients.

PMID- 9636517
TI  - Specificity of therapeutic drug monitoring of tacrolimus in kidney transplant
      patients.

PMID- 9636518
TI  - Decreasing pancreatic toxicity of tacrolimus by dosage reduction.

PMID- 9636519
TI  - Early posttransplantation renal hemodynamics in FK 506-treated kidney recipients
      with or without prior induction therapy.

PMID- 9636520
TI  - Influence of early FK 506 trough levels on glomerular hemodynamics at 3 months in
      kidney transplant recipients.

PMID- 9636521
TI  - Pharmaco-economic study of FK 506 (Prograf) and cyclosporine A Neoral in
      cadaveric renal transplantation.

PMID- 9636522
TI  - FK 506 and mycophenolate mofetil in renal transplant recipients: six-month
      results of a multicenter, randomized dose ranging trial. FK 506 MMF Dose-Ranging
      Kidney Transplant Study Group.
AB  - The effective dose of MMF with FK 506 has not been previously studied in a
      prospective, randomized, controlled setting. In the present study, we evaluated
      two different daily doses of MMF (1 and 2 g) and compared it to the historically
      conventional therapy of AZA. At 6 months post-transplant, we found no significant
      difference in the incidence of acute rejection between the AZA group and the MMF
      1 g group. However, patients who started on MMF 2 g/d had significantly delayed
      and lower incidence of acute rejection as compared to the other two groups. We
      found that patients who were initiated on MMF 2 g frequently had their dose
      lowered, primarily for gastrointestinal or hematologic symptoms; by 6 months
      after-transplant, patients in the MMF 2 g group had a mean dose of 1.5 g. It is
      unclear from this study if initiating patients on MMF 1.5 g in combination with
      FK 506 would be as effective as initiating a patient on MMF 2 g. Further studies
      of the combination of FK 506 and MMF in kidney transplant recipients to further
      define the optimal dosing regimen are warranted. In summary, the combination of
      FK 506 and MMF is well-tolerated, safe, and effective in cadaveric kidney
      transplant recipients.

PMID- 9636523
TI  - Co-administration of tacrolimus and mycophenolate mofetil in cadaveric renal
      transplant recipients.

PMID- 9636524
TI  - Lipoprotein patterns in renal transplant patients: a comparison between FK 506
      and cyclosporine A patients.

PMID- 9636525
TI  - Prospective randomized study comparing FK 506 (Prograft) and cyclosporine A
      (Neoral) as primary immunosuppression in cadaveric renal transplants at a single
      institution: interim report of the first 80 cases.

PMID- 9636526
TI  - Meta-analysis of FK 506 and mycophenolate mofetil refractory rejection trials in
      renal transplantation. Refractory Rejection Meta-Analysis Study Group.

PMID- 9636527
TI  - Pharmacokinetics of FK 506 and mycophenolic acid after the administration of a FK
      506-based regimen in combination with mycophenolate mofetil in kidney
      transplantation.

PMID- 9636528
TI  - Long-term steroid side effects in renal transplantation need a safe steroid
      withdrawal: a single-center experience.

PMID- 9636529
TI  - Renal allograft survival can be predicted by histomorphometric assessment of
      extracellular matrix in 6-month protocol biopsies.

PMID- 9636531
TI  - Differences between compliers and partial compliers: a multicenter study.

PMID- 9636530
TI  - Therapy of hyperlipidemia with lovastatin in kidney transplant patients on
      cyclosporine A immunosuppression: three-year experience.

PMID- 9636532
TI  - Is long-term chronic immunosuppression therapy detrimental in hepatitis C virus
      positive renal transplant patients?

PMID- 9636533
TI  - Failure of ganciclovir prophylaxis of primary cytomegalovirus disease in
      immunologic high-risk recipients.

PMID- 9636534
TI  - Prediction of early graft function in renal transplantation using a computer
      neural network.

PMID- 9636535
TI  - Cytomegalovirus infection and prophylaxis in renal transplantation: financial
      considerations.

PMID- 9636536
TI  - Etiology of early renal allograft dysfunction after live donor renal
      transplantation.

PMID- 9636537
TI  - Significance of serial biopsies after renal allograft in children.

PMID- 9636538
TI  - Influence of immunosuppression in HTLV-1-positive renal transplant recipients.

PMID- 9636539
TI  - Stabilization of bone mass after renal transplant with preemptive care.

PMID- 9636540
TI  - Reduced severity of acute rejection in hepatitis C virus positive renal allograft
      recipients: are milder immunosuppressive regimens advisable?

PMID- 9636541
TI  - Placebo-controlled study of a humanized anti-TAC monoclonal antibody in dual
      therapy for prevention of acute rejection after renal transplantation.

PMID- 9636542
TI  - Graft-versus-host antibody reactions in ABO unmatched renal transplants.

PMID- 9636543
TI  - Risk of acute cellular rejection after azathioprine withdrawal in stable renal
      allograft recipients on cyclosporine, azathioprine, and prednisone.

PMID- 9636544
TI  - ABO incompatible kidney transplantation on triple therapy compared with quadruple
      therapy.

PMID- 9636545
TI  - Preoperative induction therapy with oral cyclosporine for recipients of living
      related renal transplants.

PMID- 9636546
TI  - Low incidence of acute rejection in kidney grafts treated with initial quadruple
      therapy: a retrospective analysis comparing two ATGs.

PMID- 9636547
TI  - Pre- versus intraoperative application of glucocorticosteroids as inductive
      therapy in renal transplantation.

PMID- 9636548
TI  - Polyclonal antilymphocyte sera induce immune activation in human renal allograft
      recipients.

PMID- 9636549
TI  - ATGAM versus OKT3 induction therapy in cadaveric kidney transplantation: patient
      and graft survival, CD3 subset, infection, and cost analysis.

PMID- 9636550
TI  - Experience with azathioprine withdrawal after simultaneous kidney-pancreas
      transplantation.

PMID- 9636551
TI  - Effect of race and immunosuppression in renal transplantation: three-year
      survival results from a US multicenter, randomized trial. FK506 Kidney Transplant
      Study Group.

PMID- 9636552
TI  - Demographic considerations in tacrolimus pharmacokinetics.

PMID- 9636553
TI  - Donor bone marrow infusion in renal transplantation.

PMID- 9636555
TI  - Humanized, nonmitogenic OKT3 antibody, huOKT3 gamma(Ala-Ala): initial clinical
      experience.

PMID- 9636554
TI  - Adjuvant bone marrow infusion in clinical organ transplant recipients.

PMID- 9636556
TI  - Bone marrow augmentation in renal transplant recipients.

PMID- 9636557
TI  - Outcome after steroid withdrawal in renal transplant patients receiving
      tacrolimus-based immunosuppression.

PMID- 9636558
TI  - Corticosteroid cessation 1 week following renal transplantation using
      tacrolimus/mycophenolate mofetil based immunosuppression.

PMID- 9636559
TI  - Steroid withdrawal in renal transplant recipients: pro point of view.
AB  - Steroid-free immunosuppression remains an attractive goal in an era in which the
      transplant community should be promoting long-term allograft survival by reducing
      cardiovascular risk and maximizing long-term patient survival. In the
      cyclosporine era, the risks of steroid withdrawal outweighed the benefits of
      steroid withdrawal in a substantial minority of patients. A number of new
      immunosuppressants may prove to be more steroid sparing than cyclosporine alone
      and promise to increase the safety of steroid-free immunosuppression for renal
      transplant recipients.

PMID- 9636560
TI  - Oral ganciclovir in the prevention of cytomegalovirus infection in postkidney
      transplant "CMV at risk" recipients: a controlled, comparative study of two
      regimens (750 mg Bid and 500 mg Bid).

PMID- 9636561
TI  - An exploratory analysis of prognostic factors for patient outcome during the
      first year following renal transplantation. European Tacrolimus Multicentre Renal
      Study Group.

PMID- 9636562
TI  - Three-year follow-up of low dose tacrolimus oral therapy after liver
      transplantation: a single-centre experience.

PMID- 9636563
TI  - Tacrolimus (FK506)-based dual versus triple therapy following liver
      transplantation.

PMID- 9636564
TI  - One hundred children treated with tacrolimus after primary orthotopic liver
      transplantation.

PMID- 9636565
TI  - Long-term comparison of tacrolimus versus cyclosporine in liver transplantation.
      The US FK Study Group.

PMID- 9636566
TI  - Renal function in primary liver transplant recipients receiving neoral
      (cyclosporine) versus prograf (tacrolimus).
AB  - Immunosuppressive efficacy of Neoral and Prograf following primary hepatic
      transplantation was comparable. Incidence of rejection episodes, infectious
      complications, hypertension, and postoperative diabetes mellitus was comparable.
      Although clinical use of both immunosuppressants was associated with early
      compromise in renal function, no progressive renal dysfunction was observed.

PMID- 9636567
TI  - Liver transplantation under tacrolimus in infants, children, adults, and seniors:
      long-term results, survival, and adverse events in 1000 consecutive patients.

PMID- 9636568
TI  - Comparison of tacrolimus with neoral as primary immunosuppression in hepatitis C
      patients after liver transplantation.

PMID- 9636569
TI  - Successful use of tacrolimus for initial rejection episodes after liver
      transplantation.

PMID- 9636570
TI  - FK506 for primary and rescue therapy following liver transplantation.

PMID- 9636571
TI  - Rescue FK506 therapy for acute rejection and early chronic rejection after liver
      transplantation: report of 14 cases.

PMID- 9636572
TI  - Improved immunosuppression with combination tacrolimus (FK506) and mycophenolic
      acid in orthotopic liver transplantation.

PMID- 9636573
TI  - Tacrolimus and mycophenolate mofetil in clinical liver transplantation:
      experience with a steroid-sparing concept.

PMID- 9636574
TI  - Immunosuppression using tacrolimus, mycophenolate, and prednisone following
      orthotopic liver transplantation: a single-center experience.

PMID- 9636575
TI  - Treatment of cyclosporine-related adverse effects by conversion to tacrolimus
      after liver transplantation: long-term results.

PMID- 9636576
TI  - Early use and oral absorption of cyclosporine neoral after liver transplantation.

PMID- 9636577
TI  - Cyclosporine monotherapy in long-term pediatric liver transplant recipients.

PMID- 9636579
TI  - Reduced acute rejection and side effects with neoral in liver transplantation.

PMID- 9636578
TI  - Low rejection rate after hepatic transplantation achieved with a cyclosporine
      based quadruple immunosuppressive regimen.

PMID- 9636580
TI  - Experience with neoral cyclosporine through the oral route in liver
      transplantation.

PMID- 9636581
TI  - Cyclosporine versus cyclosporine microemulsion in pediatric liver transplant
      recipients.

PMID- 9636582
TI  - Lower incidence of liver graft rejection in patients on diltiazem plus
      cyclosporine therapy.

PMID- 9636583
TI  - Comparison of quadruple induction including ATG or IL-2R antibody with FK506
      based therapy after liver transplantation.

PMID- 9636584
TI  - Successful prednisone withdrawal after living-related liver transplantation.

PMID- 9636585
TI  - Risk and benefit of antibody induction therapy in combination with tacrolimus
      immunosuppression after liver transplantation.

PMID- 9636586
TI  - A randomized trial comparing anti-interleukin-2 receptor antibody and placebo for
      immunosuppressive therapy after OLT.

PMID- 9636587
TI  - Metabolic findings after liver transplantation within a randomised trial with or
      without steroids.

PMID- 9636588
TI  - The necessity for steroid induction or long-term maintenance after liver
      transplantation: the argument against.

PMID- 9636589
TI  - Effect of CsA versus FK 506 on insulin sensitivity and insulin response using a
      modeling technique.

PMID- 9636590
TI  - In vitro generation of tacrolimus metabolites and their detection in whole blood.

PMID- 9636591
TI  - Bioequivalence of a new strength tacrolimus capsule under development.

PMID- 9636592
TI  - Optimal time points for the prediction of the area-under-the-curve in liver
      transplant patients receiving tacrolimus.

PMID- 9636593
TI  - Cyclosporine peak levels provide a better correlation with the area-under-the
      curve than trough levels in liver transplant patients treated with neoral.

PMID- 9636594
TI  - Does initial graft function influence the outcome after liver transplantation?

PMID- 9636595
TI  - Impact of immunosuppression in liver transplantation across a positive
      crossmatch.

PMID- 9636596
TI  - Indications for mycophenolate mofetil therapy in hepatitis C-patients undergoing
      liver transplantation.

PMID- 9636597
TI  - Retransplantation for recurrent hepatitis C following tacrolimus or cyclosporine
      immunosuppression.

PMID- 9636598
TI  - Immunosuppression withdrawal for treatment of severe infections in liver
      transplantation.

PMID- 9636599
TI  - Immunosuppression and incidence of opportunistic pneumonias after liver
      transplantation.

PMID- 9636600
TI  - Clinical and radiological features of two cases of tacrolimus-related posterior
      leukoencephalopathy in living related liver transplantation.

PMID- 9636601
TI  - Living related liver transplantation for patients with renal failure.

PMID- 9636602
TI  - Is liposomal amphotericin B (ambisome) an effective prophylaxis of mycotic
      infections after liver transplantation?

PMID- 9636603
TI  - De novo cancer after orthotopic liver transplantation.

PMID- 9636604
TI  - Lymphoproliferative disease after liver transplantation: primary biliary
      localization.

PMID- 9636605
TI  - Hypercholesterolemia in long-term survivors of liver transplantation: a
      comparison between cyclosporine and FK 506.

PMID- 9636606
TI  - Donor-recipient sex matching and posttransplant malignancies after induction
      therapy in hepatic transplantation.

PMID- 9636607
TI  - Incidence of acute rejection in African-American liver transplant recipients.

PMID- 9636608
TI  - Influence of immunosuppression on patient outcome after liver transplantation.

PMID- 9636609
TI  - Protocol liver biopsies: the case in favour.

PMID- 9636610
TI  - The cost of rejection in liver allograft recipients.

PMID- 9636611
TI  - Cost of liver transplantation using tacrolimus.

PMID- 9636612
TI  - Conversion to tacrolimus (FK506) from cyclosporine after orthotopic lung
      transplantation.

PMID- 9636613
TI  - FK506 rescue therapy in lung transplantation.

PMID- 9636614
TI  - Comparison of neoral and sandimmun cyclosporines for de novo lung transplantation
      in cystic fibrosis patients.

PMID- 9636615
TI  - Cyclosporine A-associated thrombotic thrombocytopenic purpura following lung
      transplantation.

PMID- 9636616
TI  - Mycophenolate mofetil in lung transplantation.

PMID- 9636617
TI  - ATG induction therapy and the incidence of bronchiolitis obliterans after lung
      transplantation: does it make a difference?

PMID- 9636618
TI  - Clinical use and bioavailability of tacrolimus in heart-lung and double lung
      transplant recipients with cystic fibrosis.

PMID- 9636619
TI  - Isolated lung transplantation for end-stage pulmonary disease.

PMID- 9636620
TI  - Prevalence of malignancies after lung transplantation.

PMID- 9636621
TI  - Does cyclosporin promote the secretion of transforming growth factor-beta 1
      following pulmonary transplantation?

PMID- 9636622
TI  - National transplantation Pregnancy Registry: outcomes of pregnancies in lung
      recipients.

PMID- 9636623
TI  - Tacrolimus/mycophenolate mofetil/steroid-based immunosuppression after pancreas
      kidney transplantation with single shot antithymocyte globulin.

PMID- 9636624
TI  - Use of intravenous tacrolimus to reverse vascular rejection in kidney and
      simultaneous kidney-pancreas transplantation.

PMID- 9636625
TI  - Tacrolimus/mycophenolate provides superior immunosuppression relative to
      neoral/mycophenolate in synchronous pancreas-kidney transplantation.

PMID- 9636626
TI  - Long-term kidney and pancreas function with tacrolimus immunosuppression
      following simultaneous kidney and pancreas transplantation.

PMID- 9636627
TI  - Use of tacrolimus and mycophenolate mofetil for pancreas-kidney transplantation
      with or without OKT3 induction.

PMID- 9636628
TI  - Superior efficacy of oral ganciclovir over oral acyclovir for cytomegalovirus
      prophylaxis in kidney-pancreas and pancreas alone recipients.

PMID- 9636629
TI  - Sequential pancreas after kidney transplantation: is anti-lymphocyte induction
      therapy needed?

PMID- 9636630
TI  - Low-dose OKT3 treatment for rejection/induction in kidney and kidney-pancreas
      transplantation.

PMID- 9636632
TI  - Antibody induction therapy in pancreas transplantation.

PMID- 9636631
TI  - Evidence for microchimerism in peripheral blood, bone marrow, and skin following
      donor bone marrow/kidney-pancreas transplantation at 3 years.

PMID- 9636633
TI  - Late acute rejection episodes after vascularized pancreas transplantation.

PMID- 9636634
TI  - Mycophenolate mofetil versus azathioprine in simultaneous pancreas-kidney
      transplant recipients on cyclosporine.

PMID- 9636635
TI  - Long-term outcomes in simultaneous kidney-pancreas transplant recipients.

PMID- 9636636
TI  - Small bowel transplantation alone or with the liver in children: changes by using
      FK506.

PMID- 9636637
TI  - Immunosuppressive agents: recent developments in molecular action and clinical
      application.

PMID- 9636638
TI  - Future challenges in immunosuppression.

PMID- 9636639
TI  - Basic science aspects of chronic rejection: induction of protective genes to
      prevent development of transplant arteriosclerosis.

PMID- 9636640
TI  - Chronic rejection.

PMID- 9636641
TI  - The "infectious" tolerance pathway in organ allograft recipients.

PMID- 9636642
TI  - Tacrolimus as a primary immunosuppressive therapy in cadaveric renal
      transplantation: five years' experience at a single center.

PMID- 9636643
TI  - Mucin functions and expression in mammalian reproductive tract tissues.

PMID- 9636644
TI  - BC1 RNA protein particles in mouse brain contain two y-,h-element-binding
      proteins, translin and a 37 kDa protein.
AB  - Neural BC1 RNA is distributed in dendrites in the form of ribonucleoprotein
      particles (RNP). Recently, Han et al. reported that testis-brain RNA-binding
      protein (the mouse homologue of Translin), known to be a translational repressor,
      links a subset of mRNAs to microtubules (MTs) through binding to their y-,h
      sequence elements. We found that similar elements are also present in BC1 RNA.
      Therefore, it is possible that they also act as cis-elements, together with their
      transacting proteins, and control the transport of BC1 RNA along dendritic MTs.
      In this study, we demonstrated that two y-,h-element-binding proteins copurified
      with BC1 RNP. One was identified as mouse Translin and the other was a 37 kDa
      protein. This macromolecular assembly may constitute a transport particle for BC1
      RNA. It is also possible that BC1 RNP or Translin itself may play a regulatory
      role(s) in the translation of mRNAs within dendrites.

PMID- 9636645
TI  - Protective protein/cathepsin A loss in cultured cells derived from an early
      infantile form of galactosialidosis patients homozygous for the A1184-G
      transition (Y395C mutation).
AB  - Galactosialidosis is a human autosomal recessive lysosomal storage disease caused
      by a genetic defect of protective protein/cathepsin A (PPCA). The patients in a
      Japanese family with the severe early-infantile form of galactosialidosis were
      revealed to be homozygous for the A1184-G transition in the PPCA gene in both
      alleles, which leads to the Y395C substitution. The acid carboxypeptidase
      (cathepsin A) and lysosomal neuraminidase activities were markedly decreased in
      cultured fibroblasts and chorionic villus cells derived from the patients,
      although the decrease in beta-galactosidase activity was less. Immunoblot and
      immunocytochemical analyses showed that neither the precursor nor the mature form
      of the PPCA gene product was present in the cultured cells. The Y395C mutation
      was revealed to cause the loss of the translated product, that determines the
      severity of the clinical phenotype.

PMID- 9636646
TI  - Modulation of the growth of Plasmodium falciparum in vitro by protein
      serine/threonine phosphatase inhibitors.
AB  - To elucidate the physiological roles of the protein serine/threonine phosphatases
      of P. falciparum, first we identified and characterized phosphatase activities of
      Plasmodium falciparum enzymologically and pharmacologically. We have demonstrated
      that P. falciparum possesses phosphatase-1-like activities predominantly over
      phosphatase-2A-like activities, while erythrocytes possess mainly phosphatase-2A
      like activities. Then, we examined the effects of okadaic acid and calyculin A,
      potent inhibitors of protein phosphatase 1 and 2A, on the growth of P. falciparum
      in vitro. Both of the drugs inhibited parasite growth dose dependently. The
      manner of growth inhibition by calyculin A and okadaic acid suggested that these
      drugs inhibit parasite growth mainly by inhibiting parasite phosphatase-1-like
      activities. Both drugs were shown to inhibit the growth of three different
      developmental stages of parasites--ring forms, trophozoites, and schizonts--and
      inhibit trophozoites the most. This is the first report on P. falciparum protein
      serine/threonine phosphatase activities, which are essential to regulate the
      erythrocytic stage of parasite growth.

PMID- 9636647
TI  - Tissue-specific involvement of multiple mitochondrial DNA deletions in familial
      mitochondrial myopathy.
AB  - It is still uncertain how deleted mitochondrial DNA (mtDNA) is distributed to
      each tissue during development, although deletions of mtDNA have been extensively
      observed in various pathologic conditions. This paper presents two Japanese
      siblings with progressive external ophthalmoplegia exhibiting multiple mtDNA
      deletions. In one patient, similar multiple mtDNA deletions were found in
      skeletal muscle specimens as well as in the spinal cord but not in the
      myocardium, liver or leukocytes. A similar deletion pattern was found in the
      skeletal muscle but not in the leukocytes of the other patient. The results
      suggest the complex mechanism to generate, expand and eliminate the deleted mtDNA
      in humans.

PMID- 9636648
TI  - A steroidogenic factor-1 binding element is essential for basal human ACTH
      receptor gene transcription.
AB  - We have previously shown that the promoter of the human ACTH receptor (ACTH-R)
      contains, at -35 bp, a binding site for the steroidogenic factor 1 (SF-1), an
      orphan nuclear receptor which could be responsible for the transcriptional
      activity of this promoter. In the present study, electrophoretic mobility shift
      assays demonstrated that the sequence -43/-19 bound the SF-1 protein present in
      the nuclear extracts of adrenocortical cells. Mutation of the SF-1 binding site
      markedly reduced (40%) the basal transcription of the reporter gene in Y-1 cells
      transfected with the mutated p(-56/+22)GH construct compared to the wild-type
      construct. These results demonstrate that the SF-1 binding element present in
      this fragment is required for the basal promoter activity of the human ACTH-R
      gene. In addition, other binding elements located upstream from this
      characterized SF-1 binding site are involved in the full basal promoter activity
      of the human ACTH-R since transfection studies with a longer p(-1017/+22)GH
      construct resulted in a higher GH release than with the p(-56/+22)GH construct.

PMID- 9636649
TI  - Expression of endoglin mRNA and protein in human vascular smooth muscle cells.
AB  - Endoglin, the gene linked to the autosomal dominant vascular disorder hereditary
      hemorrhagic telangiectasia type 1 (HHT1), encodes a 95-kDa membrane-bound
      proteoglycan which binds TGF beta 1 and regulates signaling via the type I and II
      TGF beta receptors on the surface of vascular endothelial cells. Using reverse
      transcription polymerase chain reaction (RT-PCR) and Northern blot analysis we
      have shown that endoglin mRNA is expressed in both cultured human VSMCs and VSMCs
      freshly isolated from human aortas. Northern blot analysis was also used to
      demonstrate that endoglin expression decreased in serum-stimulated cultured human
      VSMCs but could be maintained by exogenous TGF beta 1. Endoglin protein
      expression in human VSMCs was shown by immunocytochemistry. These data, the first
      describing the existence of endoglin in VSMCs, suggest that through regulating
      TGF beta 1 signaling endoglin may mediate the effects of TGF beta 1 on VSMC
      behavior in vitro and in vivo.

PMID- 9636650
TI  - Endothelial cells differentially express functional CXC-chemokine receptor-4
      (CXCR-4/fusin) under the control of autocrine activity and exogenous cytokines.
AB  - Analysis of endothelial cell (EC) chemokine receptor expression by RT-PCR
      revealed that EC essentially do not express CC-chemokine receptors whereas they
      express all known CXC-chemokine receptors. Endotheliotropic functions of ligands
      for CXCR-1, CXCR-2, and CXCR-3 have previously been described. We have
      consequently performed a detailed analysis of endothelial CXCR-4 expression. CXCR
      4 is constitutively expressed by quiescent, resting EC. Cytokine stimulation
      revealed that bFGF upregulates endothelial CXCR-4 expression, whereas TNF alpha
      downregulates endothelial CXCR-4 expression. Expression of CXCR-4 mRNA as well as
      protein is also upregulated in autocrine activated, migrating bovine aortic
      endothelial cells (BAEC). Furthermore, migrating BAEC preferentially present CXCR
      4 on the cell surface as evidenced by cytochemistry and FACS analysis. Lastly,
      the monospecific CXCR-4 ligand SDF-1 was found to act as a potent inducer of EC
      chemotaxis. In summary, the data indicate that the CXCR-4/SDF-1 receptor ligand
      interaction may be an important regulator of activated endothelial cell functions
      as they occur during vascular remodeling and angiogenesis.

PMID- 9636651
TI  - Insulin-like growth factor I stimulates proliferation and Fas-mediated apoptosis
      of human osteoblasts.
AB  - In vitro studies have shown that insulin-like growth factor I (IGF-I) is a potent
      growth factor for osteoblasts, although both bone formation and resorption are
      upregulated by IGF-I in vivo. To understand the difference in the action of IGF-I
      observed in vitro and in vivo experiments, we examined the effect of IGF-I on the
      proliferation and Fas-mediated apoptosis of human osteoblasts in vitro. Human
      osteoblastic cell line MG63 and human primary osteoblast-like cells obtained from
      biopsy specimens were used as human osteoblasts. Cells were cultured with or
      without various concentrations of IGF-I followed by determination of the
      proliferative response and Fas-mediated apoptosis. IGF-I dose dependently
      stimulated the proliferation of cultured human osteoblasts. Both Fas expression
      and the degree of anti-Fas IgM-induced apoptosis of human osteoblasts was also
      augmented by IGF-I. Furthermore, the cytotoxicity of Fas ligand (FasL) cDNA
      transformants against human osteoblasts was increased when IGF-I-stimulated
      osteoblasts were used as target cells, indicating that stimulation of IGF-I
      increased functional Fas expression on human osteoblasts as well as their
      proliferation. The addition of DEVD-CHO, a specific inhibitor of CPP32, to the
      culture resulted in a significant inhibition of Fas-mediated apoptosis of both
      unstimulated and IGF-I-stimulated osteoblasts, although it did not affect the
      proliferative response or Fas expression. Our data suggest that activation of
      CPP32 is necessary for Fas-mediated apoptosis of human osteoblasts, and treatment
      of IGF-I increased this signaling pathway. In contrast, regulation of
      proliferation and Fas expression of the cells were probably not affected by CPP32
      activation. Our results suggest that IGF-I acts on cultured human osteoblasts by
      increasing their proliferation and induction of Fas-mediated apoptosis by
      neighbouring FasL+ cells such as osteoclasts, thus probably functioning as a
      local coupling factor in the bone in vivo, stimulating both bone formation and
      resorption.

PMID- 9636653
TI  - Co-amplification of nuclear pseudogenes and assessment of heteroplasmy of
      mitochondrial DNA mutations.
AB  - The potential co-amplification of actual mtDNA and nucleus-embedded mtDNA
      sequences was studied for the mtDNA domains encompassing the major disease
      causing mtDNA mutations. By using two different cell lines devoid of mtDNA (rho
      degree cell lines), it is shown that nucleus-embedded mtDNA sequences readily co
      amplified with most of the mtDNA domains encompassing disease-causing mtDNA
      mutations. The selection of mtDNA primers for specificity on rho degree cells
      constitutes a simple procedure to avoid such co-amplification. It appears
      mandatory prior to quantify mtDNA mutations, especially when delivering prenatal
      diagnosis or predictive genetic advise.

PMID- 9636652
TI  - Identification and distribution of mRNA encoding the Y1, Y2, Y4, and Y5 receptors
      for peptides of the PP-fold family in the rat intestine and colon.
AB  - Peptide YY (PYY), neuropeptide Y (NPY) and pancreatic polypeptide (PP) are
      structurally related peptides which have potent antisecretory effects in small
      and/or large intestines. Receptors mediating these effects are still unknown with
      the exception of a PYY-preferring receptor expressed in small intestinal crypts.
      In the present study, expression of recently cloned Y1, Y2, and Y5 receptors
      which have similar affinity for PYY and NPY and Y4 receptors which have a high
      affinity for PP was investigated in gut by RT-PCR analysis. The data show that
      all Y receptors are expressed in small intestine and/or colon but with specific
      distributions. Y1 receptors are only expressed in nonepithelial colonic tissue,
      whereas Y2 and Y4 receptors are present in both epithelial and nonepithelial
      tissue of the small or large intestine. In contrast, Y5 receptor expression
      appears to be restricted to epithelial crypts of the small intestine and
      nonepithelial tissue of colon. Sequencing of PCR products showed 100% identity
      with the corresponding sequences of the cloned Y1, Y4, or Y5 receptors. The PCR
      product obtained with Y2 primers from rat crypt cells showed 84% identity with
      the cloned human Y2 receptor. These data indicate a wide distribution of Y
      receptors in small intestine and colon. They also suggest that Y1, Y2, Y4, and Y5
      receptors may be responsible for still unexplained effects of PYY, NPY, or PP on
      secretion in small and large intestines.

PMID- 9636654
TI  - Free radical-scavenging properties of olive oil polyphenols.
AB  - Plants in the Mediterranean basin, such as vine and olive trees, have developed
      an array of antioxidant defences to protect themselves from environmental stress.
      Accordingly, the incidence of coronary heart disease and certain cancers is lower
      in the Mediterranean area, where olive oil is the dietary fat of choice. As
      opposed to other vegetable oils, extra virgin olive oil, which is obtained by
      physical pressure from a whole fruit, is rich in phenolic components that are
      responsible for the particular stability of the oil. We have investigated the
      scavenging actions of some olive oil phenolics, namely hydroxytyrosol and
      oleuropein, with respect to superoxide anion generation, neutrophils respiratory
      burst, and hypochlorous acid. The low EC50S indicate that both compounds are
      potent scavengers of superoxide radicals and inhibitors of neutrophils
      respiratory burst: whenever demonstrated in vivo, these properties may partially
      explain the observed lower incidence of CHD and cancer associated with the
      Mediterranean diet.

PMID- 9636655
TI  - Transcription factor NF-E2 is essential for the polyploidization of a human
      megakaryoblastic cell line, Meg-J.
AB  - Transcription factors regulating the process of megakaryocyte development remain
      largely unclarified. To clarify them further, we used a human megakaryoblastic
      cell line, Meg-J, which showed prominant polyploidization and augmented platelet
      glycoprotein (GP) Ib expression after incubation with thrombopoietin (TPO, c-mpl
      ligand) and K252a (an indolocarbasole derivative). Under these conditions, we
      analyzed the expression of the transcription factors and observed that the
      expression of NF-E2 p45, but not those of GATA-1, GATA-2, Tal-1/SCL, Evi-1, and
      MafK, was increased after TPO and K252a stimulation. Gel-shift assay confirmed
      the enhanced binding activity to the NF-E2 site. The abolishment of NF-E2 p45
      with NF-E2 antisense oligomers inhibited TPO plus K252a-induced polyploidization.
      These findings suggest that NF-E2 p45 is essential for the polyploidization of
      megakaryocytic cells.

PMID- 9636656
TI  - A hVti1 homologue: its expression depends on population doubling levels in both
      normal and SV40-transformed human fibroblasts.
AB  - A cDNA clone was isolated by differential colony hybridization from a cDNA
      library prepared from life-extended SV40-transformed human fibroblasts. The
      clone, tentatively named N-10, was 1272 bp in length coding for 232 amino acids.
      Northern analysis revealed that the expression level of N-10 was increased in
      normal senescent and life-extended SV40-transformed fibroblasts than in their
      young counterparts but was not enhanced by growth arrest. The protein fused to
      GFP (green fluorescent protein) localized in cytoplasmic granule. Enforced
      expression of N-10 resulted in premature senescence in young fibroblasts. The
      deduced amino acid sequence of N-10 was identical to the recently reported hVti1
      gene except in one amino acid: Asp24(GAC) was ours and Asn24 (AAC) was reported.
      Additional base differences were found, so we referred to our sequence as the
      hVti1 homologue. As hVti1 protein was suggested to be involved in the vesicle
      transport process, the homologue may be concerned with increased secretion of
      extracellular matrix and various cytokines associated with cellular senescence.

PMID- 9636657
TI  - Cloning and characterization of human estrogen receptor beta isoforms.
AB  - Multiple transcripts which arise from the human estrogen receptor beta (ER beta)
      gene have been characterized. Three full length isoforms of the hER beta gene,
      designated hER beta 1-3, were identified in a testis cDNA library. An additional
      two isoforms, designated hER beta 4 and hER beta 5, were identified by PCR
      amplification from testis cDNA and from the MDA-MB 435 cell line. hER beta 1
      corresponds to the previously described hER beta. All five isoforms diverge at a
      common position within the predicted helix 10 of the ligand binding domain of hER
      beta, with nucleotide sequences consistent with differential exon usage. The hER
      beta isoform mRNAs displayed a differential pattern of expression in human
      tissues and in tumor cell lines when analyzed by RT-PCR. Further characterization
      of the three full length isoforms, hER beta 1-3, by in vitro band shift studies
      indicated that the isoforms were able to form DNA-binding homodimers and
      heterodimers with each other and with the ER alpha subtype.

PMID- 9636658
TI  - The DNA-dependent protein kinase participates in the activation of NF kappa B
      following DNA damage.
AB  - The NFkB transcription factor is activated by diverse stimuli, including Ionizing
      Radiation (IR) and the cytokine TNF alpha. The role of DNA-PK, a protein kinase
      involved in the response to DNA damage, in the activation of NF kappa B by IR and
      TNF alpha was examined. In M059K cells, which express DNA-PK, NF kappa B was
      activated by both TNF alpha and IR. In M059J cells, which do not express DNA-PK,
      IR did not activate NF kappa B, whereas TNF alpha induction of NF kappa B was
      still observed. In HeLa cells, wortmannin, an inhibitor of DNA-PK, blocked the
      induction of NF kappa B by IR but not by TNF alpha. DNA-PK also phosphorylated
      the NF kappa B inhibitory proteins IkB-alpha and IkB-beta in vitro, and deletion
      analysis demonstrated that DNA-PK phosphorylates 2 distinct regions of IkB-beta.
      These results indicate that DNA-PK participates in the activation of NF kappa B
      by IR but not by TNF alpha.

PMID- 9636659
TI  - Arginase AI is upregulated in acute immune complex-induced inflammation.
AB  - Previous studies have shown high arginase activity at inflammatory sites.
      Arginase converts L-arginine to L-ornithine, sharing a common substrate with
      nitric oxide synthase. It exists as two isoforms, AI and AII. While the function
      of liver arginase (AI) in ureagenesis has been defined, the role and isoform of
      arginase in cells without a complete urea cycle are unknown. We therefore
      determined arginase isoform mRNA expression in glomerular acute immune complex
      inflammation, and its cultured constituent cells. AI was induced in nephritic
      glomeruli, and in mesangial cells stimulated with IL-4 and cAMP, and was present
      in elicited neutrophils and macrophages. AII was constitutively expressed. Our
      data strongly suggest that AI, thought to be restricted to the liver, accounts
      for high arginase activity at inflammatory sites where it may limit high output
      nitric oxide production and generate polyamines and proline essential for cell
      proliferation and matrix production. This identification of AI in inflamed tissue
      is an important step for understanding the consequences of increased arginase
      activity.

PMID- 9636660
TI  - The nucleus of HeLa cell contains tubular structures for Ca2+ signalling.
AB  - It has long been assumed that Ca2+ are translocated from the cytosol to the cell
      nucleus by a long distance to activate transcription machinery buried deep in the
      nucleoplasm. However, this model has been recently challenged. When HeLa cells
      were loaded with fluo-3, highly fluorescent spots of approximately 2 microns in
      diameter were observed in the cell nucleus while the fluo-3 signals were low in
      their neighbouring nucleoplasm as determined by confocal microscopy. These
      fluorescent spots were devoid of but usually associated with chromatin on their
      boundary. When cells were stimulated by ionomycin (1 microM), the fluo-3
      fluorescence in these spots increased faster than that in their neighbouring
      nucleoplasm. In another experiment, optical sections with hot spot(s) were used
      to construct 3-D images to study the morphology of the hot spots. Views of
      reconstruction from different angles indicated that the hot spots formed a
      tubular structure with a connection to the nucleocytoplasmic interface. Moreover,
      injection of calcium green-dextran (70 kDa), a Ca(2+)-sensitive indicator
      conjugated with an inert molecule of large molecular size, into the cytosol leads
      to a formation of signals also in a tubular shape inside the nucleoplasm. This
      suggests that the 'channels' are real inside the nucleus and they are derived
      from an invagination of the double-membraned nuclear envelope. Taken together,
      our results indicate (1) tubular structures are found inside the cell nucleus;
      (2) they are extended from the cytosol into the nucleus through the invagination
      of the double membraned nuclear envelope; (3) molecules of molecular size up to
      70 kDa could penetrate into these 'tunnels'; (4) Ca2+ can be released or
      transported into the cell nucleus through these tubular structures after
      ionomycin stimulation; and (5) the structures are usually associated with
      chromatin.

PMID- 9636661
TI  - Successful transplantation of genetically corrected DMD myoblasts following ex
      vivo transduction with the dystrophin minigene.
AB  - Myoblast transplantation and gene therapy are two promising therapeutical
      approaches for the treatment of Duchenne Muscular Dystrophy (DMD). So far, both
      strategies have met many hurdles, mainly because of immune reactions. In this
      study, we investigated a third and novel strategy based on the combination of
      these two basic ones, i.e., transplantation of genetically modified myoblasts. We
      first derived a primary culture from a muscle biopsy of a young DMD patient (3
      years old). Adenoviral-mediated dystrophin gene transfer into these DMD cultures
      and expression of the dystrophin transgene were achieved in vitro. The transduced
      cultures were then transplanted the same day in immunodeficient SCID mouse
      muscles. Three weeks following the graft, many human dystrophin-positive fibers
      were observed throughout sections of the injected muscles. However, many fibers
      expressed human MHC antigens without expressing human dystrophin due to the low
      percentage of infected primary muscle cells in vitro (even when a high MOI [400]
      was used) and to a reduction and even to a complete loss of transgene copy number
      during myoblast replication. From our results, we conclude that, although not at
      a high proportion, (1) DMD primary myoblast cultures are infectable by
      adenoviruses; (2) they can be efficiently transplanted back in a muscle, leading
      to normal fusion of infected myoblasts with the host fibers; and (3) they can
      correct the dystrophin deficiency in the host fibers by the expression of a mini
      dystrophin transgene.

PMID- 9636662
TI  - Cloning and expression pattern of chicken Pitx2: a new component in the SHH
      signaling pathway controlling embryonic heart looping.
AB  - Asymmetry along the left-right axis of the embryo is a vital feature of
      vertebrate embryogenesis. In this study, we report the isolation and
      characterization of a bicoid-related homeobox gene, cPitx2, which displays left
      right asymmetric expression during early chick embryogenesis. Asymmetric
      expression of cPitx2 is first detected at stage 7 and is restricted to mesodermal
      tissues on the left side of the embryo including the left sided lateral mesoderm,
      the left sided precardiac mesoderm, and the left half epimyocardium of the
      primitive heart. cPitx2 is also detected in the presumptive blood islands and
      endothelia of the embryonic blood vessels. Implantation of Sonic hedgehog (SHH)
      protein soaked beads on the right side of embryos induced ectopic cPitx2
      expression on that side. Based on these observations, we suggest that cPitx2 is a
      component in SHH signaling pathway and plays a role in determining left-right
      asymmetry and in vasculogenesis during avian embryogenesis.

PMID- 9636663
TI  - A novel lectin with potent immunomodulatory activity isolated from both fruiting
      bodies and cultured mycelia of the edible mushroom Volvariella volvacea.
AB  - A novel lectin has been purified from the fruiting bodies as well as cultured
      mycelia of the edible mushroom Volvariella volvacea. The lectin, designated as
      VVL, was a homodimeric protein with a molecular weight of 32 kDa as demonstrated
      by gel filtration and SDS-PAGE. VVL had no carbohydrate moiety, and its
      hemagglutinating activity was inhibited by thyroglobulin but not by simple
      carbohydrates such as monomeric or dimeric sugars. The immunomodulatory activity
      of VVL was demonstrated by its potent stimulatory activity toward murine splenic
      lymphocytes. VVL was also found to markedly enhance the transcriptional
      expression of interleukin-2 and interferon-gamma by reverse transcriptase
      polymerase chain reaction. As revealed by its N-terminal amino acid sequence, VVL
      possessed a molecular structure distinct from other immunomodulatory proteins
      previously reported in the same fungus.

PMID- 9636664
TI  - A novel mitochondrial tRNA(Phe) mutation inhibiting anticodon stem formation
      associated with a muscle disease.
AB  - We have identified a novel mitochondrial (mt) DNA mutation in the tRNA(Phe)-gene
      in a patient with an isolated mitochondrial myopathy. This T to C transition at
      position 618 disrupts a strictly conserved base pair within the anticodon stem of
      tRNA(Phe). Computer analysis showed that the affected base pair is essential for
      anticodon stem formation of tRNA(Phe). The mutant mtDNA was heteroplasmic in
      skeletal muscle (95% mutant) and peripheral blood cells (20% mutant) from the
      patient but was undetectable in blood cells from his healthy sister. The patient
      presented with ragged red fibers and reduced activities of complex I and complex
      III in skeletal muscle. The T618C mutation described here is the second found in
      this region. Both mutations affect the same base pair of the tRNA(Phe) anticodon
      stem substantiating the pathogenic nature of both mutations.

PMID- 9636665
TI  - Molecular cloning of multiple isoforms of synaptojanin 2 and assignment of the
      gene to mouse chromosome 17A2-3.1.
AB  - Synaptojanin 2 is an inositol polyphosphate 5'-phosphatase that appears to be
      regulated by alternative splicing. By screening mouse cDNA libraries derived from
      either mouse day 16 embryo or adult liver, we have identified additional
      synaptojanin 2 cDNAs that represent six new isoforms of the protein. This
      finding, together with other reports, indicates the presence of eight isoforms of
      synaptojanin 2. Sequence analysis of our cDNA clones suggests that there are at
      least two putative initiation sites and at least six different sequences coding
      for the carboxyl-terminus of the molecule. In addition, we have mapped
      synaptojanin 2 to mouse chromosome 17 band A2-3.1 by fluorescence in situ
      hybridization.

PMID- 9636666
TI  - Atrial natriuretic factor-induced amylase output in the rat parotid gland appears
      to be mediated by the inositol phosphate pathway.
AB  - In previous in vivo studies we have reported that atrial natriuretic factor
      enhanced induced salivary secretion and increased isoproterenol-induced amylase
      release in the rat suggesting that, ANF effect could be mediated by
      phosphatidylinositol hydrolysis. In the present work, the effect of ANF on rat
      parotid tissue incubated in vitro was investigated with the aim to assess whether
      the phosphoinositol pathway was involved in ANF intracellular signaling in the
      parotid gland. Results showed that ANF induced a dose dependent increase in
      amylase fractional release, which was lower than that evoked by any concentration
      of isoproterenol. Furthermore 100 nM ANF enhanced isoproterenol-evoked amylase
      release. The effect of ANF was not affected in the presence of propranolol
      suggesting the noninvolvement of the beta adrenergic receptor, which is the main
      stimulus for the output of the enzyme in the parotid gland. However, ANF
      increased phosphatidylinositol hydrolysis, which implies an increase in
      intracellular calcium, which is necessary for the achievement of maximal response
      in amylase release. This effect was abolished in the presence of neomycin
      supporting ANF direct stimulation of phospholipase C. These results suggest the
      involvement of the C type natriuretic peptide receptor coupled to phospholipase C
      in ANF evoked amylase release and ANF enhancement of the isoproterenol-induced
      output of the enzyme.

PMID- 9636667
TI  - Novel carbazole degradation genes of Sphingomonas CB3: sequence analysis,
      transcription, and molecular ecology.
AB  - The degradation of aromatic compounds by bacteria is dependent upon specific
      catabolic operons. The unique car locus isolated from Sphingomonas CB3 encodes
      the first four enzymes involved in the catabolism of the azaarene carbazole.
      These include a class II three-component dioxygenase enzyme system, a dihydrodiol
      dehydrogenase, an extradiol (meta-cleavage) dioxygenase, and a hydrolase.
      Homology of deduced amino acid sequences is closer to corresponding biphenyl
      catabolic genes than to previously characterised carbazole degradation genes.
      Gene arrangement is also identical to that found in some bph loci. The car genes
      are transcribed when carbazole is utilised as a sole carbon source, and although
      biphenyl does not serve as a growth substrate for Sphingomonas CB3 it is able to
      act as a non-metabolisable inducer of the car locus. Ecologically the car genes
      were detected in polycyclic aromatic hydrocarbon (PAH) contaminated soil
      associated with a former town gas site.

PMID- 9636668
TI  - Characterization of trypsin-modified bovine lens acylpeptide hydrolase.
AB  - Acylpeptide hydrolase, which removes the N-acetylated amino acids from peptide
      substrates was purified from bovine lens, truncated in vitro to a 55 kDa enzyme
      by trypsin digestion and characterized. The activity of the trypsin-modified
      enzyme was investigated using alpha A-crystallin and oxidized insulin A chain.
      The trypsin-modified enzyme was able to unblock alpha A-crystallin and displayed
      endoprotease activity unlike the native enzyme. SDS-PAGE analysis and amino acid
      sequencing of (3H)iPr2P-F labeled bovine lens acylpeptide hydrolase showed that
      the lens has a 55 kDa truncated form of the enzyme. The in vivo truncated form of
      the enzyme was generated by the cleavage of the Gly203-Asp204 peptide bond in the
      native enzyme.

PMID- 9636669
TI  - Identification of the catalytic triad of the protein D2 protease in Pseudomonas
      aeruginosa.
AB  - We reported recently that protein D2 (OprD) porin of Pseudomonas aeruginosa bears
      protease activity (FEBS Letters 394, 179-182, 1996). To identify the catalytic
      residues of OprD, we introduced the site-directed mutations replacing the
      putative catalytic triad His156, Asp208, and Ser296 with glutamine, asparagine,
      and alanine, respectively. The OprD proteins purified from the chromosomal oprD
      deficient mutants harboring the plasmids encoding the site-directed mutations
      showed protease activity less than 0.1% of that of the wild-type OprD. These site
      directed mutageneses caused undetectable changes in the pore-forming activity of
      OprD as measured by single-channel conductance by the planar lipid bilayer. The
      minimum inhibitory concentration of imipenem in mutants having the replaced
      catalytic triads was identical with that in the wild-type strain. On the other
      hand, introduction of the mutation at His367 replacing with glutamine, the site
      that is supposed to be unrelated to the catalytic sites, showed the unchanged
      protease activity. These results unequivocally demonstrate that OprD is the
      protease bearing porin and catalyzes the reaction at His156, Asp208, and Ser296
      residues.

PMID- 9636670
TI  - Structure of the gene encoding the human cyclin-dependent kinase inhibitor p18
      and mutational analysis in breast cancer.
AB  - The cyclin-dependent kinase (CDK) inhibitor p18 blocks progression of the cell
      cycle by associating with the cyclin D-dependent kinases CDK6 and CDK4. To better
      understand the regulation of p18 gene expression, we isolated full-length cDNA
      clones from a human BT-20 breast cancer cell cDNA library. These clones were then
      used to isolate the human gene from a human genomic DNA library. The human p18
      gene spans at least 7.5 kb and is composed of three exons, two of which encode
      the p18 protein. The genomic clone we isolated contained 5 kb of putative
      promotor sequence which directed expression of the luciferase reporter gene in
      transient transfection experiments. The longest cDNA that we isolated from BT-20
      cells contained 2103 nucleotides which corresponds to the size of the major RNA
      transcript detected by Northern analysis in these cells. Transcription start
      sites mapping to the 5' end of the putative full-length cDNA were identified by
      ribonuclease protection assays. A novel polymorphism was identified in the 3'
      untranslated region of BT-20 cell cDNA clones that contained the previously
      described codon 72 mutation. The codon 72 mutation was also detected in 3 of 35
      breast tumors analyzed using a mismatch PCR/RFLP strategy.

PMID- 9636671
TI  - Ocular lens NAD kinase: partial purification and metabolic implications.
AB  - The ocular lens displays a significant amount of NADP(H) dependent metabolic
      traffic, but the origin of this cofactor has not been established. Size exclusion
      chromatography of bovine lens crude extract on a Sephacryl S300-HR column fitted
      with an eluate concentrator revealed two bands with NAD kinase activity, based on
      enzymatic cycling with signal amplification of the column fractions using a Cobas
      Fara II centrifugal fast analyzer. Ve/Vo ratios from the chromatographic runs
      suggest that the relative molecular weight values lie within the ranges 8.91-3.98
      x 10(5) and 2.04-1.26 x 10(5), respectively, for these two bands. An
      approximately 10-fold enhancement of enzyme activity over the crude fraction is
      realized from the chromatography step. Results point to NAD kinase as the source
      generator of this anchoring and linking cofactor for the oxidative stress and
      pentose phosphate enzyme systems, respectively.

PMID- 9636672
TI  - Iron compounds after erythrophagocytosis: chemical characterization and
      immunomodulatory effects.
AB  - In humans, the lymphomyeloid system has a fundamental role on iron metabolism
      promoting its recycling due to a continuous removal of effete red blood cells.
      Additionally, one of the most intriguing aspects of metalloporphyrins in biology
      is their effect on the immune system. However, the process of erythrocyte
      catabolism is still poorly understood and needs further research. In the present
      study, we attempt to investigate the nature and the possible physiologic role of
      Fe compounds released after erythrophagocytosis during the removal of red blood
      cells. Monocyte erythrophagocytosis in vitro experiments were done to
      characterize chemically the Fe compounds present inside the cells and in the
      culture supernatants. We tested the probable immunomodulatory functions of
      erythrophagocytosis products over lymphocyte cultures activated in vitro with T
      mitogens (alpha-CD3). Data obtained from atomic absorption spectroscopy confirmed
      the presence of Fe in the culture supernatants of monocyte cultures after
      erythrophagocytosis. Also, high-spin haem complexes derived from erythrocyte
      catabolism were detected by electron paramagnetic electronic resonance. Finally,
      in vitro activated lymphocyte proliferation experiments indicate the co-mitogenic
      properties of monocyte culture supernatants after red blood cells phagocytosis.
      Thus, the results of the present work provide evidence that culture monocyte
      supernatants after in vitro erythrophagocytosis contain Fe (III) high-spin haem
      complexes and show lymphocyte proliferation co-stimulatory properties.

PMID- 9636673
TI  - Oxidative stress in patients with hepatitis, cirrhosis, and hepatoma evaluated by
      plasma antioxidants.
AB  - We have applied our method for the simultaneous detection of plasma ubiquinol-10
      (reduced form) and ubiquinone-10 (oxidized form) (S. Yamashita and Y. Yamamoto,
      Anal. Biochem. 250, 66-73, 1997) to plasmas of normal subjects (n = 16) and
      patients with chronic active hepatitis (n = 28), liver cirrhosis (n = 16), and
      hepatocellular carcinoma (n = 20) to evaluate the pressure of oxidative stress in
      these patients. The average ubiquinone-10 percentages (+/- S.D.) in total
      ubiquinone-10 and ubiquinol-10 in the four groups were 6.4 +/- 3.3, 12.9 +/-
      10.3, 10.6 +/- 6.8, and 18.9 +/- 11.1, respectively, indicating a significant
      increase in ubiquinone-10 percentage in patient groups in comparison to normal
      subjects. These results and a significant decrease in the plasma ascorbate level
      in patient groups indicate that oxidative stress is evident after the onset of
      hepatitis and the subsequent cirrhosis and liver cancer.

PMID- 9636674
TI  - APS kinase from Arabidopsis thaliana: genomic organization, expression, and
      kinetic analysis of the recombinant enzyme.
AB  - The gene encoding 5'-adenylylsulfate (APS) kinase (EC 2.7.1.25) (APK) was cloned
      from Arabidopsis thaliana. There is a single APK locus in A. thaliana. The coding
      sequence of the gene is composed of 7 exons, interrupted by 6 introns. A
      transcriptional initiation site was detected 120 bp 5' of the initiation codon.
      APK mRNA is slightly more abundant in leaves than in roots of A. thaliana and its
      level does not change in response to sulfur starvation. The APK protein,
      synthesized in vitro, is able to enter isolated intact chloroplasts. Recombinant
      APS kinase shows maximal activity at 10 microM APS with 5 mM ATP, but it is
      inhibited at APS concentrations above 10 microM. The inhibition is alleviated at
      higher ATP concentrations. Reciprocal plot analysis showed that the theoretical
      Vmax is approximately 1.2 mumol min-1 mg-1 at 25 degrees C, pH 8.0; the K(m)
      values are 3.6 microM APS and 1.8 mM ATP.

PMID- 9636675
TI  - In vitro inhibition of Ras-Raf association by short peptides.
AB  - Seven amino acid peptides were tested as in vitro inhibitors of oncogenic Ras-Raf
      association. The sequences of these peptides were derived from the H-Ras effector
      region (amino acids 25 to 51) and the Ras binding domain of Raf-1 (amino acids 64
      to 105). Eleven out of the twenty-one Ras 7-mers tested inhibited formation of
      the Ras-Raf complex by at least 20% at 100 microM. The most potent of these
      inhibitory peptides contained the effector residues 32 to 37 or 40 to 45. Of the
      Raf-1 peptides tested, only the 94-ECCAVFR-100 and 95-CCAVFRL-101 peptides were
      significant inhibitors of Ras-Raf binding. The 95-101 Raf peptide had an IC50
      value of 7 microM and also inhibited Ras-RalGDS binding. Analysis of the 95-101
      peptide showed that its inhibitory activity required at least one cysteine
      followed by several hydrophobic residues. Our results demonstrate the feasibility
      of using small molecules as inhibitors of Ras protein-protein interactions.

PMID- 9636676
TI  - Chiral inversion of 1-hydroxyethylpyrene enantiomers mediated by enantioselective
      sulfotransferases.
AB  - The benzylic alcohol 1-hydroxyethylpyrene (1-HEP) is activated to a mutagen by
      sulfotransferases. The sulfuric acid ester formed is difficult to detect, as it
      is rapidly hydrolysed back to the alcohol. Incubation of the individual
      enantiomers of 1-HEP with human hydroxysteroid sulfotransferase (hHST) or
      estrogen sulfotransferase (hEST), expressed in bacteria, led to the formation of
      the other enantiomer. The rates of sulfation were determined from the initial
      rates of chiral inversion of the alcohol, knowing that hydrolysis follows an SN1
      mechanism and therefore produces racemic alcohol. hEST showed high
      enantioselectivity for S-1-HEP, whereas hHST strongly preferred the R-enantiomer.
      The rates of sulfation of the preferred enantiomers were high, similar to those
      for the prototype substrates of hEST (beta-estradiol) and hHST
      (dehydroepiandrosterone). Moreover, after a 30-min incubation of S-1-HEP with
      hEST, 95% of the recovered alcohol showed the R-configuration, indicating that
      several cycles of sulfation and hydrolysis had led to the depletion of one
      enantiomer and to the enrichment of the other enantiomer.

PMID- 9636677
TI  - Effect of laminin on the nuclear localization of nucleolin in rat intestinal
      epithelial IEC-6 cells.
AB  - Laminin is a major component of extracellular matrix. The mechanism of action of
      laminin on cell proliferation, differentiation, and migration is not fully
      understood. In this study, we investigated the role of extracellular matrix,
      especially laminin, on the cellular localization of the nuclear protein,
      nucleolin, and on cell proliferation. Immunofluorescent and western blot analysis
      indicated that nucleolin was translocated most efficiently to the nucleus in the
      small intestinal rat epithelial cell line (IEC-6) when cultured on laminin-coated
      plates. Specifically, nucleolin was observed predominantly in cytoplasm in the
      cells cultured without laminin. In contrast, nuclear localization was observed in
      the cells cultured on laminin. This effect of laminin on nucleolin translocation
      was time-dependent. Laminin was also observed to stimulate proliferation of IEC-6
      cells in serum free medium. Our results suggest that laminin alters the
      distribution of nucleolin which may be an early signal for cell proliferation.

PMID- 9636678
TI  - Differentiation of forbidden T cell clones and granulocytes in the parenchymal
      space of the liver in mice treated with estrogen.
AB  - Estrogen was administered to B6 (NK1.1+ strain), BALB/c (Mls-1b2a, V beta 3+
      cells being forbidden clone), or (B6 x BALB/c) F1 mice (1 mg/mouse). On days 3
      and 10, the number of cells yielded by the liver doubled, whereas that yielded by
      the thymus decreased prominently. The numbers of cells in the spleen, bone
      marrow, and blood were unchanged. c-kit+ stem cells, which give rise to
      multilineage cells, were present in the liver and bone marrow. The proportion of
      such c-kit+ cells in the liver increased while that in the bone marrow decreased
      on day 3. Therefore, the absolute number of c-kit+ stem cells increased
      severalfold in the liver and clusters of lymphoid cells became visible in the
      parenchymal space. At that time, the expression of recombination activating gene
      1 and -2 mRNAs became prominent. Reflecting these phenomena, the number and
      proportion of IL-2R beta+ CD3int cells (i.e., primordial T cells) increased in
      the liver on days 3 and 10. An increase in the number of proportion of such
      CD3int cells was seen even in the thymus and uterus. In parallel with the
      increase of CD3int cells, the proportion of granulocytes also increased in
      various organs on day 3. Forbidden clones were present in either the NK1.1+ or
      the NK1.1- subset of CD3int cells in (B6 x BALB/c) F1 mice treated with estrogen
      and liver mononuclear cells in such mice acquired potent cytotoxicity against
      syngeneic thymocytes. These results reveal that estrogen has the ability to
      potentiate the generation of self-reactive T cells and granulocytes in the liver
      and other organs.

PMID- 9636679
TI  - Intermediate TCR cells can induce graft-versus-host disease after allogeneic bone
      marrow transplantation.
AB  - Mice fall victim to GVHD when subjected to immunosuppressive treatment and
      injected with allogeneic bone marrow cells. A major population of cells
      associated with GVHD is known to be T cells. However, whether such T cells are of
      thymic or extrathymic origin is obscure. We applied two immunosuppressive
      conditions, 9 and 6.5 Gy irradiation, to C3H/He mice (H-2k). Bone marrow cells
      for injection were obtained from C57BL/6 (B6) mice (H-2b). The 9-Gy mice were
      reconstituted by lymphocytes of donor origin and showed GVHD, whereas 6.5-Gy mice
      were reconstituted by lymphocytes of recipient origin and showed mild GVHD. The
      liver was the organ where the reconstitution of lymphocytes occurred efficiently,
      and a major lymphocyte subset was intermediate (int) CD3 cells (i.e., CD3int
      cells) in both mice. CD3int cells had the properties of extrathymic T cells,
      showing the phenotype of NK1.1 + CD3int using invariant V alpha 14 chain. In 6.5
      Gy mice, allogeneic cells were rejected by extrathymic T cells of recipient
      origin. The stored CD3int cells from the liver of 9-Gy mice evoked similar GVHD
      when transferred into 6.5-Gy irradiated C3H/He mice. These results suggest that
      CD3int cells of extrathymic origin are a major population for the induction of
      GVHD under immunosuppressive conditions.

PMID- 9636680
TI  - Internalization of iscom-borne antigens and presentation under MHC class I or
      class II restriction.
AB  - Exogenous nonreplicating antigens (Ag) incorporated into immunostimulating
      complexes (iscoms) induce CTL responses under MHC class I restriction. A
      requirement for inducing CTL responses is that the Ag is delivered to the cytosol
      of antigen-presenting cells (APC), a route restricted to endogenously produced
      Ag. To investigate the mechanisms by which iscoms elicit MHC class I-restricted
      responses, the intracellular distribution of influenza virus envelope proteins
      incorporated in iscoms (flu-iscoms) or in micelles (flumicelles) was studied in
      vitro using murine peritoneal cells (PEC). Ultrathin sections of cells pulsed
      with biotinylated flu-iscoms or flu-micelles were analyzed by electron microscopy
      after detection of the biotin label by reaction with streptavidin-gold. PEC
      pulsed with flu-iscoms showed a pattern of scattered gold particles distributed
      in clear and dense vesicles as well as in the intracellular space but not
      associated with organelles. In cells pulsed with flu-micelles, Ag was also
      detected in most cellular compartments but at a considerably lower concentration.
      The intracellular distribution of particulate Ag in iscom or micelle form was
      confirmed by lysis and differential centrifugation of Ag-pulsed APC. Furthermore,
      P815 cells pulsed with flu-iscoms were lysed by specific immune effectors showing
      that the iscom-Ag was processed and presented by class I-expressing APC. Flu
      iscoms were internalized about 50-fold more efficiently than ovalbumin iscoms
      (ovaiscoms) suggesting that the nature of the protein and/or the presence of
      cellular receptors are important factors influencing the capacity of APC to take
      up iscom-borne proteins. PEC accounted for the most active internalization of
      iscom-borne Ag, although splenic dendritic cells and B cells also took up
      fluiscoms with remarkable efficiency.

PMID- 9636681
TI  - Activation of p21ras/MAPK signal transduction molecules decreases with age in
      mitogen-stimulated T cells from rats.
AB  - Signal transduction is ubiquitously involved in the initiation of physiological
      signals that lead to growth and proliferation of cells. The signaling cascade
      mediated by the mitogen-activated protein kinase (MAPK) is considered essential
      for T cell growth and function. Therefore, it was of interest to determine the
      influence of age on the induction of MAPK in mitogen-activated T cells. T cells
      from young (4-6 months) and old (24-26 months) rats responded to concanavalin A
      (Con A) stimulation by increasing MAPK, c-jun amino terminal kinase (JNK), and
      p21ras activities. The time course of induction of MAPK/JNK and p21ras activities
      was similar in T cells isolated from young and old rats. The induction of JNK
      activity did not change significantly with age; however, the induction of MAPK
      and p21ras activities was significantly less (50 to 65%) in T cells from old rats
      than in T cells from young rats. Although the relative protein levels of p42 and
      p44 MAPK did not change with age, the proportion of the phosphorylated p44 MAPK
      decreased with age. In addition, it was found that the in vitro kinase activities
      of the T cell receptor-associated protein tyrosine kinase Lck (p56Lck) and ZAP-70
      but not Fyn (p59Fyn) were lower in T cells from old rats than in T cells from
      young rats. The decline in activities of these signaling molecules with age was
      not associated with changes in their corresponding protein levels. Thus, our
      results demonstrate that aging alters the activation of the signal transduction
      cascade that leads to T cell activation.

PMID- 9636682
TI  - Functional consequences of the SHP-1 defect in motheaten viable mice: role of NF
      kappa B.
AB  - To define the functional consequences of the src-homology domain-1 protein (SHP
      1) defect, we examined cytokine production and NF-kappa B activity in motheaten
      viable (Mev) mice. We found elevated levels of interleukin-6 (IL-6), interleukin
      10 (IL-10), tumor necrosis factor (TNF), and interferon-gamma (IFN-gamma) in Mev
      mice sera and cultured B and T cells compared to littermate control adult mice.
      The levels of interleukin-2 (IL-2) detected in Mev sera and activated Mev T cells
      were decreased, but IL-2 receptor expression was increased. We then evaluated the
      activity of NF-kappa B and found that this protein is highly expressed in Mev B
      and T cells. To determine if NF-kappa B had a role in causing the elevated levels
      of cytokines in Mev mice, we treated activated Mev T cells with an NF-kappa B
      decoy and found that cell culture treatment with the decoy resulted in
      significant reduction of the secretion of IL-6, GM-CSF, and TNF, but not IFN
      gamma. Therefore, our data show that Mev mice secrete elevated levels of
      inflammatory cytokines, which can be mediators in the development of the Mev
      clinical disorder, and that NF-kappa B has an important role in this process,
      impacting upon the regulation of the immune response.

PMID- 9636683
TI  - Cytokine release by macrophages after interacting with CSF-1 and extracellular
      matrix proteins: characteristics of a mouse model of inflammatory responses in
      vitro.
AB  - Extracellular matrix (ECM) proteins play a key role at sites of inflammation
      where they regulate the inflammatory properties of infiltrating leukocytes.
      Previous data indicated that the macrophage colony-stimulating factor (CSF-1 or M
      CSF) primed subpopulations of mononuclear phagocytes (MNP) for differential
      inflammatory responses and rendered defined populations extremely sensitive to
      secondary stimulation as measured by cytokine gene expression. In this report, we
      focus on the question whether CSF-1 modified the inflammatory responsiveness of
      elicited peritoneal macrophages (PM phi), as a defined subpopulation of MNP, to
      secondary stimulation by ECM proteins as a component of inflammatory lesions. It
      was seen that CSF-1-primed PM phi responded to fibronectin (FN) and collagen type
      IV (COL IV) in vitro by releasing large amounts of IL-6 but released only minimal
      quantities when exposed to vitronectin (VN) or to untreated plastic surfaces. TNF
      alpha and GM-CSF proteins were not released. Preincubation of the PM phi with CSF
      1 or 10% FBS for up to 12 h prior to exposure to ECM proteins was shown to
      further enhance the release of IL-6 when the cells were cultured with FN but to
      result in a loss of secretory activity when placed on COL IV. In addition,
      preincubated PM phi in contact with FN were shown to release TNF-alpha but not GM
      CSF. CSF-1 did not enhance VLA 4 (alpha 4 beta 1 or CD49d) but enhanced VLA 5
      (alpha 5 beta 1 or CD49e) expression. However, blocking with either anti-VLA 4 or
      VLA 5 monoclonal antibodies inhibited the IL-6 response. These data suggest that
      CSF-1 primes elicited PM phi for differential expression of adhesion molecules
      that are required for binding to individual ECM proteins and for modulating
      inflammatory responses of MNP.

PMID- 9636684
TI  - Vaccination with dendritic cells inhibits the growth of hepatic metastases in B6
      mice.
AB  - Dendritic cells (DC) are specialized antigen-presenting cells that can activate
      naive and mature T-cells, induce cellular immunity, and stimulate strong
      antitumor reactions in vivo. This study was undertaken to examine the function of
      DC vaccines in suppressing the growth of hepatic metastases in C57BL/6 mice.
      Experimental mice received two i.v. doses of 1 x 10(6) bone marrow-derived DC,
      either unpulsed or pulsed with MCA-106 fibrosarcoma cell lysates, on days -14 and
      -7. Controls were injected with HBSS. Hepatic metastases were established on day
      0 through intrasplenic injections of 1 x 10(5) MCA-106 tumor cells. Animals were
      sacrificed on day 21 and their livers were excised to assess tumor burden.
      Splenocytes from DC-treated groups were cytotoxic against MCA-106 cells, but not
      against the L929 and CT26 (syngeneic fibroblast and colon tumor, respectively)
      cell lines. All control mice developed grossly evident hepatic metastases, while
      62 and 44% of the mice receiving MCA-106 cell lysate-pulsed DC and unpulsed DC
      vaccines, respectively, were completely free of tumor. Mean hepatic mass for the
      controls, including tumor, was almost double that for treated animals. Antibody
      depletion of either CD4+ or CD8+ lymphocytes abrogated the protective effect of
      the vaccine. This study demonstrates that immunization with DC confers cellular
      immunity, with both CD4+ and CD8+ T-cells playing a significant role, and impedes
      the subsequent establishment and growth of hepatic metastases in mice. The
      antitumor capabilities of DC justify their use in immunotherapeutic vaccines
      against human cancers.

PMID- 9636685
TI  - Vitamin A inhibits cytokines produced by type 1 lymphocytes in vitro.
AB  - The effect of vitamin A (retinol) on cell-mediated immune responses was studied.
      As an experimental model, Leishmania major infection in mice was used. In this
      model, resistant mouse strains develop a type 1 response, while susceptible
      strains develop a type 2 response. Using lymph node cells and T-cell lines
      developed from infected susceptible and resistant mice, it was found that vitamin
      A inhibited lymphocyte proliferation in a dose-dependent manner. By separately
      incubating antigen-presenting cells and T cells with vitamin A, it was shown that
      the inhibitory effect was on the T cells. Type 1 cytokine (IFN-gamma, GM-CSF, IL
      2) secretion in vitro in response to stimulation with specific antigen was also
      inhibited in a dose-dependent manner, whereas secretion of type 2 cytokines (IL-4
      and IL-10) was not affected by vitamin A. The inhibitory effect was also observed
      in PMA-stimulated (but not Con A-stimulated) lymphocytes and was noticeable even
      if the vitamin was added as late as 24 h after initiation of the incubation
      period. Since PMA does not operate via a receptor-coupled signaling pathway but
      rather directly affects the protein kinase C (PKC) pathway, we have measured the
      effect of vitamin A on PKC in situ activation. Incubation of lymphocytes and
      antigen in the presence of vitamin A caused inhibition of PKC isoenzymes
      translocation to the particulate cell fraction, as measured by immunoblotting.
      The results presented indicate that, when added to cell cultures in vitro,
      vitamin A inhibits only secretion of type 1 but not type 2 cytokines, possibly
      through an inhibitory effect on protein kinase C activity.

PMID- 9636686
TI  - Interleukin (IL)-15 enhances antibody-dependent cellular cytotoxicity and natural
      killer activity in neonatal cells.
AB  - Interleukin (IL)-15 is a novel cytokine that is very similar to IL-2 in receptor
      specificity and biological activities. We compared the ability of IL-15 and IL-12
      to enhance the cytotoxicity of neonatal (cord blood) and adult mononuclear cells
      (MNC) in both natural killer (NK) and antibody-dependent cellular cytotoxicity
      (ADCC) assays. Incubation with IL-15 (10 ng/ml) or IL-12 (1 ng/ml) for 18 h
      enhanced the NK activity (using K562 target cells) of both cord and adult MNC,
      increasing cord cell cytotoxicity threefold. Similar enhancement was seen in ADCC
      assays using erythrocyte targets and NK-resistant CEM cells coated with HIV gp
      120 antigen. Incubation of cord cells with IL-15 or IL-12 for 1 week increased
      both NK and ADCC, although the combination produced less of an effect than either
      cytokine alone. IL-15 also increased the percentage of CD16+/CD56+ cells after 1
      week incubation. This enhancement of NK and ADCC activities and the number of NK
      cells by IL-15 suggests it may be clinically useful in treating immunodeficient
      patients.

PMID- 9636687
TI  - B-cell superantigens may play a role in B-cell development and selection in the
      young rabbit appendix.
AB  - In order to develop protective antibodies against a wide range of potentially
      infectious pathogens, the young rabbit must diversify a limited initial
      repertoire by somatic mechanisms (the high copy number primary repertoire). The
      majority of rabbit B cells produce heavy chain variable regions by rearranging
      the VHa allotype-encoding VH1 gene. Thus in normal rabbits the majority of serum
      immunoglobulins bear VHa allotype (due to VH1 FR1 and FR3 sequences). The young
      rabbit appendix is a site of diversification of rearranged VH genes by gene
      conversion-like and somatic hypermutation mechanisms. The newly generated B cells
      probably undergo selection processes that involve foreign and self-antigens and
      superantigens. We find preferential expansion and survival of B cells in normal
      and VH-mutant ali/ali rabbits based on their heavy chain FR1 and FR3 sequences
      (VHa allotype). This selection may involve "superantigen"-like interactions with
      endogenous as well as exogenous ligands.

PMID- 9636689
TI  - An anergic cytotoxic T lymphocyte clone exhibits granule exocytosis-mediated
      cytotoxicity.
AB  - T cell receptor (TCR) occupancy in the absence of a costimulatory signal
      transforms T helper (Th) cells or cytotoxic T lymphocytes (CTL) into a state of
      anergy. The anergic T cells are unable to produce cytokines; nevertheless, they
      maintain their killing activity. We investigated the mechanisms through which
      anergic CTL causes lysis of target cells. Treatment of a CTL clone with phorbol
      myristate acetate and calcium ionophore A23187 (P/A) transformed these cells to
      anergic cells. While the anergic CTL clones failed to secrete TNF-alpha in the
      culture supernatant, they were still able to kill antigen-specific target cells
      via a granule exocytosis-mediated pathway. This was evident by the synthesis of
      perforin mRNA and release of N-alpha-benzyloxycarbonyl-L-lysine thiobenzyl ester
      esterase by these cells. The anergic CTL clone also showed a low degree of Fas
      mediated lysis of normal target cells. In addition, we generated anergic bulk CTL
      by treatment with P/A and observed that the anergic bulk CTL failed to produce
      TNF upon antigen stimulation, but retained target killing activity via a granule
      exocytosis mechanism. Our results suggest that the killing mechanisms of anergic
      CTL are mediated to a large extent by a granule exocytosis-mediated pathway.

PMID- 9636688
TI  - A humanised therapeutic CD4 mAb inhibits TCR-induced IL-2, IL-4, and IL-10
      secretion and expression of CD25, CD40L, and CD69.
AB  - The actions of a humanised therapeutic CD4 mAb YHB.46 on T cell activation were
      investigated in vitro. Soluble YHB.46 IgG or YHB.46-derived F(ab')2 fragments
      caused inhibitions of up to 100% of the proliferation of purified CD4+ T cells
      activated with immobilised CD3 mAb. The inhibitory effects of the CD4 mAb were
      equally potent in both CD45RA+ and CD45RO+ T cell subset proliferation assays.
      Inhibitory effects on DNA synthesis were nto explicable by increased T cell
      apoptosis. YHB.46 was inhibitory even when added 70 h after exposure of cells to
      immobilised CD3 mAb, but it had little effect on IL-2 receptor-driven
      proliferation signals. The CD4 mAb inhibited the CD3-induced expression of the
      CD25 and CD69 activation markers on the T cell surface and suppressed CD40 ligand
      expression, but not that of CD25 and CD69, when their expression was induced by
      phorbol ester plus ionomycin. YHB.46 also exerted a profound inhibitory effect on
      the production of IL-2, IL-4, and IL-10, irrespective of whether T cells were
      activated with CD3 mAb or with phorbol ester plus ionomycin. The inhibitory
      effects of YHB.46 on CD4+ T cell proliferation were partially prevented by the
      addition of exogenous IL-2 or autologous monocytes and were completely prevented
      by activating T cells with a novel CD3-CD28 bivalent F(ab')2 reagent. However,
      the inhibitory effects of YHB.46 on T cell proliferation were equipotent in the
      presence or the absence of CTLA-4Ig, showing that the CD4 mAb was not acting on
      CD28-induced activation signals per se. Our results show that the inhibitory
      effects of YHB.46 on T cell activation do not involve CD28 or IL-2 receptor
      signalling, but are directed at the TCR-mediated G0-G1 transition. These findings
      in vitro predict that YHB.46 may act as a potent immunosuppressant in the
      clinical context.

PMID- 9636690
TI  - A thymic nurse cell-specific monoclonal antibody.
AB  - A thymic epithelial cell line (tsTNC-1) that maintains the ability to selectively
      bind and internalize immature alpha beta TCRloCD4+CD8+ thymocytes in vitro was
      used in the development of a monoclonal antibody that is specific to the cell
      surface of thymic nurse cells (TNCs) in the thymus. The rat monoclonal antibody
      ph91 showed specificity to cells of the subcapsular region of the thymic cortex.
      Upon mechanical dispersion of the thymus in vitro, ph91 recognized cells
      displaying the multicellular morphology unique to TNCs. Ph91 staining was not
      detected on fresh thymocytes, stromal cells of the inner thymic cortex, thymic
      medullary cells, B cells or fibroblasts. Ph91 recognized a 43-kDa protein on the
      surface of TNCs. Exposure of tsTNC-1 cells to ph91 in tissue culture
      significantly reduced the percentage of binding of the alpha beta TCRloCD4+CD8+
      thymocyte subset previously shown to target TNCs. In organ culture, ph91 reduced
      the viability of developing thymocytes by 70%. The largest reduction was found in
      the alpha beta TCR+CD4+CD8+ thymocyte subset. These results represent the first
      report of a TNC-specific monoclonal antibody. Further, the antigen to which ph91
      binds may play a role in the process of thymocyte binding and their subsequent
      internalization which is unique to TNCs and important to the T cell developmental
      process.

PMID- 9636691
TI  - In vitro thymocyte maturation is associated with reduced cellular susceptibility
      to Fas-mediated apoptosis.
AB  - We have developed a novel system in which the susceptibility of murine thymocytes
      to Fas-mediated apoptosis can be modulated. Thymocyte susceptibility to Fas
      decreases under in vitro culture conditions that promote aspects of thymocyte
      maturation. The hyporesponsive state is specific for the Fas pathway, since
      cellular susceptibility to other apoptotic stimuli is not reduced.
      Hyporesponsiveness is not associated with alterations in the thymocyte subset
      distribution, decreased expression of full-length Fas protein, or alterations in
      FADD, Bcl-2, or Bcl-XL expression. Hyporesponsiveness is overcome by increasing
      the strength of the Fas cross-linking stimulus, leading us to propose that
      reduced thymocyte susceptibility to apoptosis results from altered Fas signaling.
      The block in Fas signaling resides proximal to ceramide generation, since Fas
      hyporesponsive thymocytes are susceptible to ceramide-induced apoptosis. Further
      characterization of Fas signaling in these in vitro cultured thymocytes may
      facilitate the identification of factors regulating the susceptibility of wild
      type lymphocytes to Fas.

PMID- 9636692
TI  - Regulation of cyclooxygenase-2 and endogenous cytokine expression by bacterial
      lipopolysaccharide that acts in synergy with c-kit ligand and Fc epsilon receptor
      I crosslinking in cultured mast cells.
AB  - Emerging evidence has suggested the pivotal role of mast cells in a host defense
      against bacterial infection. In this paper, we report that bacterial
      lipopolysaccharide (LPS) is a potent enhancer of the cytokine- and IgE-dependent
      delayed responses of IL-3-dependent mouse bone marrow-derived cultured mast cells
      (BMMC). LPS, although showing minimal effects, significantly augmented the c-kit
      ligand (KL)- or IgE-dependent expression of cyclooxygenase (COX)-2 and the
      attendant delayed PGD2 generation, with IL-10 and IL-4 acting as potentiating and
      inhibitory cytokines, respectively. The COX-2-inducing activity of LPS was
      mimicked by exogenous IL-1 beta. Assessment of endogenous cytokine induction
      revealed that IL-1 beta expression was stimulated by either LPS or exogenous IL-1
      beta. IL-6 expression occurred in parallel with COX-2 expression. IL-10
      expression, which lagged behind COX-2 expression, depended on exogenous IL-10,
      but not on LPS and IL-1 beta. Thus, LPS and IL-1 beta exhibited similar
      biological activities in terms of COX-2 and endogenous cytokine expression.
      However, adding an antibody against the type I IL-1 receptor to BMMC, which
      abrogated the effects of IL-1 beta, failed to neutralize the effects of LPS.
      These results suggest that LPS activates BMMC through the signal transduction
      pathway shared with exogenous IL-1 beta, rather than exerting its action
      indirectly via the production of endogenous IL-1 beta.

PMID- 9636693
TI  - Enhancement of T-cell-mediated arthritis in mice by treatment with a monoclonal
      antibody against interleukin-4.
AB  - We investigated a role for interleukin-4 (IL-4) in T-cell-mediated arthritis by
      employing a monoclonal antibody against IL-4 (11B11 mAb). As a model of T-cell
      mediated arthritis, antigen-induced arthritis (AIA) in mice was used. To induce
      AIA, mice were immunized with methylated bovine serum albumin (mBSA) (day 0). On
      day 14, the animals were intraarticularly injected with mBSA into the ankle
      joint. 11B11 mAb was daily injected i.p. for a period of 10 days, commencing on
      the day of immunization with mBSA. We found that treatment with 11B11 mAb
      significantly enhanced the severity of AIA. The enhanced arthritis was also
      observed in mice injected i.v. with lymphoid cells from mBSA-immunized mice,
      followed by the intraarticular challenge injection of mBSA. The enhancement of
      AIA by the anti-IL-4 mAb was associated with a significant increase in the
      proliferative response of lymphoid cells to mBSA in mice treated with the mAb.
      The secretion of IL-4 as well as IL-5 decreased in 11B11 mAb-treated mice, while
      the production of IFN-gamma and IL-2 increased following mAb treatment. Thus, the
      neutralization of IL-4 by an anti-IL-4 mAb appeared to enhance AIA, suggesting a
      role for IL-4 in downregulating T-cell-mediated joint inflammation.

PMID- 9636694
TI  - Lymphokine regulation of activation-induced apoptosis in T cells of IL-2 and IL
      2R beta knockout mice.
AB  - Recent studies using IL-2R alpha knockout mice have generated conflicting results
      regarding the hypothesis that IL-2/IL-2R interaction is obligatory for the
      development of AICD, which plays a central and pivotal role in maintaining
      peripheral tolerance. A relevant consequence of AICD defect is the demonstrated
      development of autoimmune lymphoproliferative disease in IL-2, IL-2R alpha, and
      IL-2R beta knockout mice, but not in IL-4, IL-7, or IL-7R knockout mice. Whether
      IL-4, IL-7, or IL-15 can provide the required signal for AICD development is
      addressed here using IL-2 and IL-2R beta knockout mice. Lymph node T cells from
      knockout mice were stimulated with Con A plus rIL-1 for 3 days and then
      maintained in high concentrations of rIL-4, rIL-7, or rIL-15 for an additional 3
      days before they were subjected to AICD analysis. Our study demonstrates that IL
      4, IL-7, and IL-15 can transduce signals critical for AICD development in the
      absence of IL-2-mediated signals. The requirement for relatively high
      concentrations of these lymphokines suggests their limited role in maintaining
      peripheral T cell tolerance, thus explaining the differential expression of
      autoimmune lymphoproliferative disease in the targeted mutant strains described
      above.

PMID- 9636695
TI  - A structural switch in a mutant insulin exposes key residues for receptor
      binding.
AB  - Despite years of effort to clarify the structural basis of insulin receptor
      binding no clear consensus has emerged. It is generally believed that insulin
      receptor binding is accompanied by some degree of conformational change in the
      carboxy-terminal of the insulin B-chain. In particular, while most substitutions
      for PheB24 lead to inactive species, glycine or D-amino acids are well tolerated
      in this position. Here we assess the conformation change by solving the solution
      structure of the biologically active (GluB16, GlyB24, desB30)-insulin mutant. The
      structure in aqueous solution at pH 8 reveals a subtle, albeit well-defined
      rearrangement of the C-terminal decapeptide involving a perturbation of the B20
      23 turn, which allows the PheB25 residue to occupy the position normally taken up
      by PheB24 in native insulin. The new protein surface exposed rationalizes the
      receptor binding properties of a series of insulin analogs. We suggest that the
      structural switch is forced by the structure of the underlying core of species
      invariant residues and that an analogous rearrangement of the C-terminal of the B
      chain occurs in native insulin on binding to its receptor.

PMID- 9636696
TI  - Inhibition of Escherichia coli RNA polymerase by bacteriophage T4 AsiA.
AB  - The 10 kDa bacteriophage T4 antisigma protein AsiA binds the Escherichia coli RNA
      polymerase promoter specificity subunit, sigma 70, with high affinity and
      inhibits its transcription activity. AsiA binds to sigma 70 primarily through an
      interaction with sigma 70 conserved region 4.2, which has also been implicated in
      sequence-specific recognition of the -35 consensus promoter element. Here we show
      that AsiA forms a stable ternary complex with core RNA polymerase (RNAP) and
      sigma 70 and thus does not inhibit sigma 70 activity by preventing its binding to
      core RNAP. We investigated the effect of AsiA on open promoter complex formation
      and abortive initiation at two -10/-35 type promoters and two "extended -10"
      promoters. Our results indicate that the binding of AsiA to sigma 70 and the
      interaction of sigma 70 region 4.2 with the -35 consensus promoter element of 
      10/-35 promoters is mutually exclusive. In contrast, AsiA has much less effect on
      open promoter complex formation and abortive initiation from extended -10
      promoters, which lack a -35 consensus element and do not require sigma 70
      conserved region 4.2. From these results we conclude that T4 AsiA inhibits E.
      coli RNAP sigma 70 holoenzyme transcription at -10/-35 promoters by interfering
      with the required interaction between sigma 70 conserved region 4.2 and the -35
      consensus promoter element.

PMID- 9636697
TI  - The major coat protein of filamentous bacteriophage f1 specifically pairs in the
      bacterial cytoplasmic membrane.
AB  - Filamentous bacteriophage are long, thin single-stranded DNA viruses that infect
      male strains of Escherichia coli without killing the host. Each phage contains
      approximately 2700 copies of the major coat protein, pVIII, which exists as a 5.2
      kDa cytoplasmic membrane protein prior to incorporation into phage. Studies from
      a number of groups analyzing the behavior of wild-type and mutant pVIII in
      detergents suggested that pVIII might pair under these conditions. In order to
      test whether pVIII molecules pair in vivo in the cytoplasmic membrane, four
      plasmidencoded pVIII variants were constructed in which specific residues in the
      transmembrane region were mutated to cysteine in an attempt to stabilize any pair
      via disulfide bridges. Variants A35C and I39C were unable to complement phage
      with an amber mutation in gene VIII. The I39C variant was unable to be packaged
      into phage particles even though it was inserted into the membrane. In the case
      of A35C, the inability to complement was not due to a packaging defect because
      the variant protein could be packaged into phage in the presence of wild-type
      pVIII. Western blot analysis of cytoplasmic membrane samples revealed that the
      A35C variant formed stable disulfide dimers in vivo. Expression of A35C
      interfered with wild-type phage infection, indicating that the assembly machinery
      may recognize the disulfide dimers in some non-productive way. The results
      indicate that pVIII may specifically pair along a particular face in the
      cytoplasmic membrane prior to assembly; however, these pairs must be able to be
      separated in order for normal assembly to occur.

PMID- 9636698
TI  - Mutations affecting cooperative DNA binding of phage HK022 CI repressor.
AB  - Cooperative protein-DNA interactions play critical roles in gene regulation in
      all organisms. Among the best-studied cooperative interactions is that of phage
      lambda repressor, which binds cooperatively to two adjacent operators. Similar
      cooperative interactions are also shown by several other lambdoid phage
      repressors, including HK022 CI repressor, which we study here. This protein has a
      much higher degree of cooperativity than seen with lambda repressor, and previous
      evidence has suggested that cooperativity may play roles in HK022 gene regulation
      that have no parallel in lambda. We have isolated several cooperativity or Coop-
      mutations in HK022 cI. These mutant proteins were partially defective in vivo for
      binding to two adjacent operators, but normal or nearly so for binding to a
      single operator. Two mutations showed mutual suppression, in that the double
      mutation had wild-type behavior. Analysis of several purified mutant proteins
      showed that they were also defective for cooperative binding in vitro.
      Unexpectedly, the mutant proteins showed an altered pattern of in vitro binding
      to DNA at non-operator sites. Several of them also increased the rate of specific
      repressor cleavage. We propose a conformational model in which the various
      functions of the wild-type protein are carried out by differing conformations;
      these conformations are normally in balance, and the mutations perturb this
      balance.

PMID- 9636700
TI  - Quantitative analysis of DNase I digestion patterns of oligo- and
      polynucleosomes.
AB  - DNase I digestion of unlabelled chromatin has been used to determine the
      orientation of nucleosomes in the higher-order structure of chromatin. DNA
      digestion patterns were analysed quantitatively and compared with simulation
      curves that were generated with the experimentally obtained rate constants for
      cutting inside nucleosomes and the half-height widths of the bands. The rate
      constants for cutting at the linker DNA were varied to fit the experimental
      curves. By comparing the digestion profiles of polynucleosomes, oligonucleosomes
      and H1/H5-depleted oligonucleosomes we have been able to distinguish between
      protection caused by H1/H5 histones only and protection caused by the higher
      order structure. By the nature of this method the area protected by H1/H5
      histones appears symmetrical around the centre of the nucleosomal DNA on the dyad
      axis (position S[0]), but it can also be interpreted as a superposition of two
      separate protected areas that are symmetrical around position S[0]. Protection by
      the higher-order structure shows that the nucleosomes are oriented with their
      S[0] positions inside the 30 nm fibre and that there is a minimum number of
      nucleosomes required for this structure to be formed. We have also found that the
      linker DNA is cut in a continuous (non-periodical) way and that there are
      considerable amounts of nucleosomes at discrete distances of multiples of ten
      nucleotides (10a nt) as well as stretches of nucleosomes positioned either at
      random or at distances of (10a + 5)nt.

PMID- 9636699
TI  - Trifluoroethanol stabilizes the pH 4 folding intermediate of sperm whale
      apomyoglobin.
AB  - 2,2,2-Trifluoroethanol (TFE) is known to stabilize peptide helices by
      strengthening hydrogen bonds. On the other hand, TFE destabilizes native
      proteins, as we confirm here, presumably by weakening the hydrophobic
      interaction. The stability of the pH 4 folding intermediate of apomyoglobin is
      known to depend both on the strength of the individual A, G, and H helices and on
      hydrophobic interactions between helices. We ask which effect of TFE dominates in
      this case: strengthening helices or weakening hydrophobic interactions between
      helices? Protein stability is measured by denaturant-induced unfolding curves,
      and two-state unfolding is tested by monitoring both far-UV CD and tryptophan
      fluorescence emission. Low concentrations of TFE strongly stabilize the pH 4
      folding intermediate. Moreover, low concentrations of TFE compensate for helix
      destabilizing mutations in the A and G helices. Consequently, enhancing helix
      propensity, rather than weakening the hydrophobic interaction, is the dominant
      effect of TFE on the folding intermediate. This result agrees with earlier
      mutational evidence that helix propensities are very important in determining the
      stability of the pH 4 intermediate. Although TFE destabilizes native
      holomyoglobin, as well as native lysozyme and ribonuclease A, nevertheless, TFE
      stabilizes native apomyoglobin.

PMID- 9636701
TI  - Trade-off between segregational stability and metabolic burden: a mathematical
      model of plasmid ColE1 replication control.
AB  - A model of ColE1 copy number control has been developed where molecular details
      of replication are connected both to segregational stability and metabolic
      burden. Efficient replication control reduces copy number variation and increases
      segregational stability for a given average copy number. Copy number variation is
      predicted to depend on the type of inhibition mechanism as well as RNA I and RNA
      II turnover rate constants. It is shown that when both RNA I and RNA II
      transcription frequencies and the rate constant for degradation of free RNA I are
      very large, a hyperbolic inhibition mechanism must compensate with a 1.4 times
      greater average copy number to obtain the same segregational stability as an
      exponential inhibition mechanism. How sensitively the replication frequency
      responds to changes in RNA I concentration depends on the type of inhibition
      mechanism and the number of attempts to form an RNA II replication primer per
      plasmid and cell cycle. If RNA I is too stable, it will not follow changes in
      plasmid concentration closely, and when the transcription frequency for RNA I is
      only slightly higher than for RNA II, RNA I concentration becomes randomized. In
      both these cases, the proportionality between the single cell RNA I and plasmid
      concentrations is lost and this impairs copy number control. Thresholds in the
      rate for degradation of free RNA I as well as in RNA I and RNA II transcription
      frequencies have been computed, where an increase in these rate constants has a
      negligible effect on segregational stability but a corresponding decrease leads
      to segregational disaster. This indicates that there exists a well defined
      optimal set of rate constants where the regulation system works well without
      excessive metabolic load. A number of new experiments are suggested to address
      features of particular importance for the evolution of ColE1 copy number control.

PMID- 9636702
TI  - Synthesis and characterisation of oligodeoxynucleotides containing thio analogues
      of (6-4) pyrimidine-pyrimidinone photo-dimers.
AB  - A method for the preparation of an oligodeoxynucleotide, 20 bases in length,
      containing centrally located thio analogues of (6-4) pyrimidine-pyrimidinone
      thymine photo-dimers is reported. The approach is based on the selective
      irradiation, at 350 nm, of a Tp4ST (4ST = 4-thiothymidine) step within a 20-mer
      having the sequence: d(ACTCGGACCT(4sT)CGCTGTGAT). Conversion of the S5-(6-4)/S5
      thietane pyrimidine-pyrimidinone, initially formed, to its S5-Dewar isomer is by
      a subsequent irradiation at 300 nm. Both of the photo-dimer-containing
      oligonucleotides were purified by HPLC (ion exchange and reverse phase) and
      characterised by base composition analysis. The S5-(6-4)/S5-thietane pyrimidine
      pyrimidinone containing 20-mer has a characteristic UV absorbance at 320 nm and
      exhibits strong fluorescence when excited at this wavelength. As expected,
      conversion to the S5-Dewar isomer abolished both the 320 nm absorbance and the
      fluorescence emission. The lengths of the oligonucleotides produced allowed the
      formation of stable double-stranded DNA, by hybridisation to a complementary
      sequence. Examination of these duplexes by circular dichroism spectroscopy showed
      that they formed B-DNA, with little changes to their gross structure as compared
      to the parent duplex. However, local structural perturbations in the region of
      the photo-dimer cannot be excluded. The S5-(6-4)/S5-thietane photoproduct lowered
      the tm by 10.5 deg. C and the Dewar isomer by 12 deg. C. The degree of curvature
      induced in the DNA sequence by the introduction of the photo-dimers was assessed
      by analysing the migration of modified and unmodified multimer ladders on
      polyacrylamide gels. Both photoproducts induced considerable bending into the
      DNA. A comparison with a six-base-pair T tract, a bending standard that has a
      known bend angle of 19 degrees, gave values of around 47 degrees for the S5-(6
      4)/S5-thietane product and about 28 degrees for the S5-Dewar isomer.

PMID- 9636703
TI  - DNA binding discrimination of the murine DNA cytosine-C5 methyltransferase.
AB  - Mammalian DNA cytosine-C5 methyltransferase modifies the CpG dinucleotide in the
      context of many different genomic sequences. A rigorous DNA binding assay was
      developed for the murine enzyme and used to define how sequences flanking the CpG
      dinucleotide affect the stability of the enzyme:DNA complex. Oligonucleotides
      containing a single CpG site form reversible 1:1 complexes with the enzyme that
      are sequence-specific. A guanine/cytosine-rich 30 base-pair sequence, a mimic of
      the GC-box cis-element, bound threefold more tightly than an adenine/thymine-rich
      sequence, a mimic of the cyclic AMP responsive element. However, the binding
      discrimination between hemi- and unmethylated forms of these DNA substrates was
      small, as we previously observed at the K(m)DNA level (Biochemistry, 35, 7308
      7315 (1996)). Single-stranded substrates are bound much more weakly than double
      stranded DNA forms. An in vitro screening method was used to select for CpG
      flanking sequence preferences of the DNA methyltransferase from a large,
      divergent population of DNA substrates. After five iterative rounds of increasing
      selective pressure, guanosine/cytosine-rich sequences were abundant and
      contributed to binding stabilization for at least 12 base-pairs on either side of
      a central CpG. Our results suggest a read-out of sequence-dependent
      conformational features, such as helical flexibility, minor groove dimensions and
      critical phosphate orientation and mobility, rather than interactions with
      specific bases over the course of two complete helical turns. Thus, both studies
      reveal a preference for guanosine/cytosine deoxynucleotides flanking the cognate
      CpG. The enzyme specificity for similar sequences in the genome may contribute to
      the in vivo functions of this vital enzyme.

PMID- 9636704
TI  - The effects of salt on the TATA binding protein-DNA interaction from a
      hyperthermophilic archaeon.
AB  - This study investigates the thermodynamics of the interaction of the TATA box
      binding protein (TBP) from Pyrococcus woesei (Pw) with an oligonucleotide
      containing a specific binding site. Pw is a hyperthermophilic archeal organism
      which exists under conditions of high salt and high temperature. A measurable
      protein-DNA interaction only occurs at high salt concentrations. Isothermal
      titration calorimetric binding studies were performed under a range of salts
      (potassium chloride, potassium phosphate, potassium acetate and sodium acetate)
      at varying concentrations (0.8 to 1.6 M). At the high salt concentrations used
      the observed equilibrium binding constant increases with increasing salt
      concentration. This is very different to the effect reported for all other
      protein-DNA interactions which have been studied at lower salt concentrations.
      Thermodynamic data suggest that the protein-DNA interaction at high salt
      concentration is accompanied by the removal of large numbers of water molecules
      from the buried hydrophobic surface area. In addition, the involvement of ions
      appears to influence the binding which can be explained by binding of cations in
      the interface between the electrostatically negative lateral lobes on the protein
      and the negatively charged DNA.

PMID- 9636705
TI  - Solution structure of a non-palindromic 16 base-pair DNA related to the HIV-1
      kappa B site: evidence for BI-BII equilibrium inducing a global dynamic curvature
      of the duplex.
AB  - 1H and 31P NMR spectroscopy have been used together with molecular modelling to
      determine the fine structure of a non-palindromic 16 bp DNA containing the NF
      kappa B binding site. Much emphasis has been placed upon NMR optimization of both
      two-dimensional 31P NMR techniques to extract structural information defining the
      phosphodiester backbone conformation and selective homonuclear 2D COSY
      experiments to determine sugar conformations. NMR data show evidence for a
      dynamic behaviour of steps flanking the ten base-pairs of the NF-kappa B binding
      site. A BI-BII equilibrium at these steps is demonstrated and two models for each
      extreme conformation are proposed in agreement with NMR data. In the refined BII
      structures, the NF-kappa B binding site exhibits an intrinsic curvature towards
      the major groove that is magnified by the four flanking steps in the BII
      conformation. Furthermore, the base-pairs are translated into the major groove.
      Thus, we present a novel mode of dynamic intrinsic curvature compatible with the
      DNA curvature observed in the X-ray structure of the p50-DNA complex.

PMID- 9636706
TI  - Genome structure of mycobacteriophage D29: implications for phage evolution.
AB  - Mycobacteriophage D29 is a lytic phage that infects both fast and slow-growing
      mycobacterial species. The complete genome sequence of D29 reveals that it is a
      close relative of the temperate mycobacteriophage L5, whose sequence has been
      described previously. The overall organization of the D29 genome is similar to
      that of L5, although a 3.6 kb deletion removing the repressor gene accounts for
      the inability of D29 to form lysogens. Comparison of the two genomes shows that
      they are punctuated by a large number of insertions, deletions, and substitutions
      of genes, consistent with the genetic mosaicism of lambdoid phages.

PMID- 9636707
TI  - Identification of target promoters for the Bacillus subtilis sigma X factor using
      a consensus-directed search.
AB  - The promoter selectivity of RNA polymerase (RNAP) can be altered by the
      association with alternative sigma subunits. Bacillus subtilis hosts a multitude
      of sigma factors, several of which coordinate the complex developmental program
      culminating in endospore formation. Genome sequencing has revealed an
      unanticipated seven new sigma factors of the highly divergent extracytoplasmic
      function (ECF) sub-family. Virtually nothing is known regarding either the
      promoter selectivity or the target genes for these newly identified sigma
      factors. We have used saturation mutagenesis to define a promoter consensus for
      recognition by one such ECF sigma factor, sigma X. The resulting consensus
      sequence was used to identify candidate sigma X target sites. Three newly
      identified sigma X-dependent promoters precede genes encoding regulatory
      proteins: an AbrB homolog (Abh), a putative response regulator aspartate
      phosphatase (RapD), and a regulator of autolysin expression (LytR). sigma X also
      contributes to the expression of CsbB, a putative membrane-bound glucosyl
      transferase that is partially controlled by the sigma B stress response sigma
      factor. Since LytR modulates the expression of the major autolytic amidase and
      CsbB may function in peptidoglycan synthesis or modification, we suggest that
      sigma X participates in the regulation of peptidoglycan synthesis and turnover.

PMID- 9636708
TI  - Different pathways for protein degradation by the FtsH/HflKC membrane-embedded
      protease complex: an implication from the interference by a mutant form of a new
      substrate protein, YccA.
AB  - Escherichia coli FtsH (HflB) is a membrane-bound and ATP-dependent zinc
      metalloproteinase, which forms a complex with a pair of periplasmically exposed
      membrane proteins, HflK and HflC. It is the protease that degrades uncomplexed
      forms of the SecY subunit of protein translocase. Here, we characterized a new
      class of SecY-stabilizing mutation on the E. coli chromosome. The mutation
      (yccA11) is an internal deletion within a gene (yccA) known as an open reading
      frame for a hydrophobic protein with putative seven transmembrane segments. The
      YccA protein was found to be degraded in an FtsH-dependent manner in vivo and in
      vitro, whereas the YccA11 mutant protein, lacking eight amino acid residues
      within the amino-terminal cytoplasmic domain, was refractory to the degradation.
      The yccA11 mutation exhibited partial dominance when overexpressed. Cross
      linking, co-immunoprecipitation, and histidine tagging experiments showed that
      YccA11 as well as YccA can associate with both the FtsH and the HflKC proteins.
      Thus, the mutant YccA protein appeared to compete with SecY for recognition by
      the FtsH proteolytic system and the residues deleted by the yccA mutation are
      required for the initiation of proteolysis by FtsH. Interestingly, the inhibitory
      action of YccA11 was mediated by HflKC, since the deletion of hflK-hflC
      suppressed the yccA11 phenotype. The yccA11 mutation stabilized subunit a of the
      proton ATPase F0 segment as well, but not the CII protein of bacteriophage lambda
      or the sigma 32 protein. From these results we suggest that there are at least
      two pathways for FtsH-dependent protein degradation, only one of which (probably
      for membrane proteins) is subject to the HflKC-dependent interference by the
      YccA11 mutant substrate.

PMID- 9636709
TI  - Rat GTP cyclohydrolase I is a homodecameric protein complex containing high
      affinity calcium-binding sites.
AB  - Recombinant rat liver GTP cyclohydrolase I has been prepared by heterologous gene
      expression in Escherichia coli and characterized by biochemical and biophysical
      methods. Correlation averaged electron micrograph images of preferentially
      oriented enzyme particles revealed a fivefold rotational symmetry of the doughnut
      shaped views with an average particle diameter of 10 nm. Analytical
      ultracentrifugation and quantitative scanning transmission electron microscopy
      yielded average molecular masses of 270 kDa and 275 kDa, respectively. Like the
      Escherichia coli homolog, these findings suggest that the active enzyme forms a
      homodecameric protein complex consisting of two fivefold symmetric pentameric
      rings associated face-to-face. Examination of the amino acid sequence combined
      with calcium-binding experiments and mutational analysis revealed a high
      affinity, EF-hand-like calcium-binding loop motif in eukaryotic enzyme species,
      which is absent in bacteria. Intrinsic fluorescence measurements yielded an
      approximate dissociation constant of 10 nM for calcium and no significant binding
      of magnesium. Interestingly, a loss of calcium-binding capacity observed for two
      rationally designed mutations within the presumed calcium-binding loop of the rat
      GTP cyclohydrolase I yielded a 45% decrease in enzyme activity. This finding
      suggests that failure of calcium binding may be the consequence of a mutation
      recently identified in the causative GTP cyclohydrolase I gene of patients
      suffering from dopa responsive dystonia.

PMID- 9636710
TI  - Structure of the Drosophila projectin protein: isoforms and implication for
      projectin filament assembly.
AB  - The protein composition of the various muscle types in Drosophila melanogaster
      has been studied quite thoroughly and the analysis has revealed many differences
      involving the usage of muscle specific isoforms of a given protein, as well as
      the presence of proteins restricted to one muscle type. Drosophila projectin, the
      giant protein component of the third filament is quite unusual as it not only
      shows specific isoforms in various muscle types, but these isoforms are located
      at different sarcomeric locations, I band in the IFM and A band in synchronous
      muscles. This may suggest distinct functions for the projectin protein in various
      muscles, as well as a different set of protein interactions for each projectin
      isoform. Projectin is encoded by a single gene and the isoforms were proposed to
      be the result of alternative splicing of a primary transcript. Here, we report
      the nearly complete sequence of Drosophila projectin, as well as the possible
      splicing patterns used to generate different isoforms. The overall domain
      organization in projectin is composed of repeated motifs I and II in a few
      specific patterns, similar to its Caenorhabditis homolog, twitchin. Sequence
      similarity between twitchin and projectin further suggests how some domains may
      possibly be important for protein interactions and/or functions. Alternative
      splicing operates at the COOH terminus, leading to a shorter projectin protein
      lacking some of the terminal motifs II and unique sequence. These isoforms are
      discussed in view of projectin differential size and localization.

PMID- 9636711
TI  - Structural studies of binding site tryptophan mutants in the high-affinity
      streptavidin-biotin complex.
AB  - Previous thermodynamic and computational studies have pointed to the important
      energetic role of aromatic contacts in generating the exceptional binding free
      energy of streptavidin-biotin association. We report here the crystallographic
      characterization of single site tryptophan mutants in investigating structural
      consequences of alterations in these aromatic contacts. Four tryptophan residues,
      Trp79, Trp92, Trp108 and Trp120, play an important role in the hydrophobic
      binding contributions, which along with a hydrogen bonding network and a flexible
      binding loop give rise to tight ligand binding (Ka approximately 10(13) M-1). The
      crystal structures of ligand-free and biotin-bound mutants, W79F, W108F, W120F
      and W120A, in the resolution range from 1.9 to 2.3 A were determined. Nine data
      sets for these four different mutants were collected, and structural models were
      refined to R-values ranging from 0.15 to 0.20. The major question addressed here
      is how these mutations influence the streptavidin binding site and in particular
      how they affect the binding mode of biotin in the complex. The overall folding of
      streptavidin was not significantly altered in any of the tryptophan mutants. With
      one exception, only minor deviations in the unbound structures were observed. In
      one crystal form of unbound W79F, there is a coupled shift in the side-chains of
      Phe29 and Tyr43 toward the mutation site, although in a different crystal form
      these shifts are not observed. In the bound structures, the orientation of biotin
      in the binding pocket was not significantly altered in the mutant complex.
      Compared with the wild-type streptavidin-biotin complex, there were no additional
      crystallographic water molecules observed for any of the mutants in the binding
      pocket. These structural studies thus suggest that the thermodynamic alterations
      can be attributed to the local alterations in binding residue composition, rather
      than a rearrangement of binding site architectures.

PMID- 9636712
TI  - Structures of two novel crystal forms of Naja naja naja phospholipase A2 lacking
      Ca2+ reveal trimeric packing.
AB  - Three crystal forms of Naja naja naja phospholipase A2 were discovered through
      random crystallization screening, including two heretofore uncharacterized forms.
      The crystallization conditions for both of these novel crystal forms are Ca(2+)
      free whereas previously reported conditions include Ca2+. One of the new crystal
      forms has a cubic lattice in the space group P2(1)3 (a = b = c = 69.24 A), the
      other has an orthorhombic lattice in the space group P2(1)2(1)2(1) (a = 67.22 A,
      b = 73.48 A, c = 87.52 A) and a previously characterized crystal belong to the
      tetragonal space group P4(3)2(1)2 (a = b = 88.6 A, c = 107.4 A). The structure
      from the cubic crystal form has been determined to 1.8 A and refined to an R
      factor of 17% while the structure from the orthorhombic form has been determined
      to 2.65 A and has been refined to an R-factor of 21%. The determination of the
      cubic structure extends the resolution to which structures of this molecule have
      been determined from 2.3 A to 1.8 A. The two newly determined structures, in
      combination with the previously determined structure, generate an informative
      structural ensemble from which structural changes due to Ca2+, which is required
      for catalysis, and the effect of crystal contacts on side-chain conformations and
      oligomeric association can be inferred. Both of the newly determined structures
      reveal a trimeric oligomer as observed in the tetragonal structure; this appears
      to be a unique feature of the Naja naja naja enzyme.

PMID- 9636713
TI  - Crystal structure of ribosomal protein S8 from Thermus thermophilus reveals a
      high degree of structural conservation of a specific RNA binding site.
AB  - S8 is one of the core ribosomal proteins. It binds to 16 S RNA with high affinity
      and independently of other ribosomal proteins. It also acts as a translational
      repressor in Escherichia coli by binding to its own mRNA. The structure of
      Thermus thermophilus S8 has been determined by the method of multiple isomorphous
      replacement at 2.9 A resolution and refined to a crystallographic R-factor of
      16.2% (Rfree 27.5%). The two domains of the structure have an alpha/beta fold and
      are connected by a long protruding loop. The two molecules in the asymmetric unit
      of the crystal interact through an extensive hydrophobic core and form a tightly
      associated dimer, while symmetry-related molecules form a joint beta-sheet of
      mixed type. This type of protein-protein interaction could be realized within the
      ribosomal assembly. A comparison of the structures of T. thermophilus and
      Bacillus stearothermophilus S8 shows that the interdomain loop is eight residues
      longer in the former and reveals high structural conservation of an extensive
      region, located in the C-terminal domain. From mutational studies this region was
      proposed earlier to be involved in specific interaction with RNA. On the basis of
      these data and on the comparison of the two structures of S8, it is proposed that
      the three-dimensional structure of specific RNA binding sites in ribosomal
      proteins is highly conserved among different species.

PMID- 9636714
TI  - The three-dimensional structure of the nitrogen regulatory protein IIANtr from
      Escherichia coli.
AB  - The bacterial rpoN operon codes for sigma 54, which is the key sigma factor that,
      under nitrogen starvation conditions, activates the transcription of genes needed
      to assimilate ammonia and glutamate. The rpoN operon contains several other open
      reading frames that are cotranscribed with sigma 54. The product of one of these,
      the 17.9 kDa protein IIANtr, is homologous to IIA proteins of the
      phosphoenolpyruvate:sugar phosphotransferase (PTS) system. IIANtr influences the
      transcription of sigma 54-dependent genes through an unknown mechanism and may
      thereby provide a regulatory link between carbon and nitrogen metabolism. Here we
      describe the 2.35 A X-ray structure of Escherichia coli IIANtr. It is the first
      structure of a IIA enzyme from the fructose-mannitol family of the PTS. The
      enzyme displays a novel fold characterized by a central mixed parallel/anti
      parallel beta-sheet surrounded by six alpha-helices. The active site His73 is
      situated in a shallow depression on the protein surface.

PMID- 9636715
TI  - Determination of the three-dimensional solution structure of Raphanus sativus
      antifungal protein 1 by 1H NMR.
AB  - Raphanus sativus Antifungal Protein 1 (Rs-AFP1) is a 51 amino acid residue plant
      defensin isolated from radish (Raphanus sativus L.) seeds. The three-dimensional
      structure in aqueous solution has been determined from two-dimensional 1H NMR
      data recorded at 500 MHz using the DIANA/REDAC calculation protocols.
      Experimental constraints consisted of 787 interproton distances extracted from
      NOE cross-peaks, 89 torsional constraints from 106 vicinal interproton coupling
      constants and 32 stereospecific assignments of prochiral protons. Further
      refinement by simulated annealing resulted in a set of 20 structures having
      pairwise root-mean-square differences of 1.35(+/- 0.35) A over the backbone heavy
      atoms and 2.11(+/- 0.46) A over all heavy atoms. The molecule adopts a compact
      globular fold comprising an alpha-helix from Asn18 till Leu28 and a triple
      stranded beta-sheet (beta 1 = Lys2-Arg6, beta 2 = His33-Tyr38 and beta 3 = His43
      Pro50). The central strand of this beta-sheet is connected by two disulfide
      bridges (Cys21-Cys45 and Cys25-Cys47) to the alpha-helix. The connection between
      beta-strand 2 and 3 is formed by a type VIa beta-turn. Even the loop (Pro7 to
      Asn17) between beta-strand 1 and the alpha-helix is relatively well defined. The
      structure of Raphanus sativus Antifungal Protein 1 features all the
      characteristics of the "cysteine stabilized alpha beta motif". A comparison of
      the complete structure and of the regions important for interaction with the
      fungal receptor according to a mutational study, is made with the structure of
      gamma-thionin, a plant defensin that has no antifungal activity. It is concluded
      that this interaction is both electrostatic and specific, and some possible
      scenarios for the mode of action are given.

PMID- 9636716
TI  - Conformational stability and thermodynamics of folding of ribonucleases Sa, Sa2
      and Sa3.
AB  - Ribonucleases Sa, Sa2, and Sa3 are three small, extracellular enzymes produced by
      different strains of Streptomyces aureofaciens with amino acid sequences that are
      50% identical. We have studied the unfolding of these enzymes by heat and urea to
      determine the conformational stability and its dependence on temperature, pH,
      NaCl, and the disulfide bond. All three of the Sa ribonucleases unfold reversibly
      by a two-state mechanism with melting temperatures, Tm, at pH 7 of 48.4 degrees C
      (Sa), 41.1 degrees C (Sa2), and 47.2 degrees C (Sa3). The Tm values are increased
      in the presence of 0.5 M NaCl by 4.0 deg. C (Sa), 0.1 deg. C (Sa2), and 7.2 deg.
      C (Sa3). The Tm values are decreased by 20.0 deg. C (Sa), 31.5 deg. C (Sa2), and
      27.0 deg. C (Sa3) when the single disulfide bond in the molecules is reduced. We
      compare these results with similar studies on two other members of the microbial
      ribonuclease family, RNase T1 and RNase Ba (barnase), and with a member of the
      mammalian ribonuclease family, RNase A. At pH 7 and 25 degrees C, the
      conformational stabilities of the ribonucleases are (kcal/mol): 2.9 (Sa2), 5.6
      (Sa3), 6.1 (Sa), 6.6 (T1), 8.7 (Ba), and 9.2 (A). Our analysis of the stabilizing
      forces suggests that the hydrophobic effect contributes from 90 to 110 kcal/mol
      and that hydrogen bonding contributes from 70 to 105 kcal/mol to the stability of
      these ribonucleases. Thus, we think that the hydrophobic effect and hydrogen
      bonding make large but comparable contributions to the conformational stability
      of these proteins.

PMID- 9636717
TI  - A graph-theoretic algorithm for comparative modeling of protein structure.
AB  - The interconnected nature of interactions in protein structures appears to be the
      major hurdle in preventing the construction of accurate comparative models. We
      present an algorithm that uses graph theory to handle this problem. Each possible
      conformation of a residue in an amino acid sequence is represented using the
      notion of a node in a graph. Each node is given a weight based on the degree of
      the interaction between its side-chain atoms and the local main-chain atoms.
      Edges are then drawn between pairs of residue conformations/nodes that are
      consistent with each other (i.e. clash-free and satisfying geometrical
      constraints). The edges are weighted based on the interactions between the atoms
      of the two nodes. Once the entire graph is constructed, all the maximal sets of
      completely connected nodes (cliques) are found using a clique-finding algorithm.
      The cliques with the best weights represent the optimal combinations of the
      various main-chain and side-chain possibilities, taking the respective
      environments into account. The algorithm is used in a comparative modeling
      scenario to build side-chains, regions of main chain, and mix and match between
      different homologs in a context-sensitive manner. The predictive power of this
      method is assessed by applying it to cases where the experimental structure is
      not known in advance.

PMID- 9636718
TI  - X-ray diffuse scattering and rigid-body motion in crystalline lysozyme probed by
      molecular dynamics simulation.
AB  - Rigid-body motions are determined from a 1 ns molecular dynamics simulation of
      the unit cell of orthorhombic hen egg-white lysozyme and their contribution to X
      ray diffuse scattering intensities are examined. Using a dynamical cluster
      technique, groups of backbone atoms that move as approximately rigid bodies are
      derived from the intramolecular interatomic fluctuation matrix. These groups tend
      to be local in the sequence or connected by disulphide bonds, and contain on
      average five residues each, X-ray diffuse scattering patterns, which are
      sensitive to collective motions, are calculated from the full simulation
      trajectory (including all the protein degrees of freedom). The results reproduce
      the main features of the experimental scattering. Diffuse scattering is also
      calculated from fitted trajectories of the rigid bodies. The full simulation
      diffuse scattering and atomic displacements are found to be well reproduced by a
      model in which the backbone atoms form the rigid groups determined using the
      dynamical cluster technique and the individual side-chains behave as separate
      rigid bodies: the resulting R-factor with the full simulation scattering is 5%.
      Quantitatively poorer agreement is obtained from trajectories in which the
      secondary structural elements of the protein are considered rigid. Rigid whole
      molecule and domain motions make only minor contributions to the protein atom
      displacements. Finally, correlations in the interatomic fluctuations are examined
      directly using a canonical method.

PMID- 9636719
TI  - [Talking with our readers].

PMID- 9636720
TI  - [Magnetic resonance of the elbow: technique optimization and definitions of
      normal anatomical features and their variations].
AB  - INTRODUCTION: MRI is a very accurate technique to study the elbow joint, tendon,
      ligament and chondral structures. In the last years elbow disorders were
      described by several MR investigators, while we studied MR capabilities in
      depicting normal elbow anatomy. This investigation might permit the correct
      differentiation of normal from abnormal MR patterns. MATERIAL AND METHODS: Eleven
      healthy volunteers (6 men and 5 women, mean age: 27.5 years) were examined. All
      studies were performed on a 1.5 T imager (Magnetom SP 4000) with two types of
      receiver: the knee coil was used in 7 volunteers examined in the prone position,
      with the arm above their head, the elbow extended and the forearm supine and the
      shoulder coil was used in 4 volunteers examined in the prone position, with the
      arm above their head, the elbow flexed and the forearm prone. We acquired T1
      weighted SE sequences (TR/TE = 690/15 ms, FA 90 degrees, MA 256 x 512, NEX 2,20 3
      mm sections with .3-mm interslice gap, FOV 20-22 cm) on the axial, coronal and
      sagittal planes and T2-weighted GE sequences (TR/TE = 450/10 ms, MA 256 x 256, 3
      NEX, 18 4-mm sections with .4-mm interslice gap, FOV 13-18 cm) on the coronal
      plane. Two MR-expert radiologists studied the images and identified the main
      anatomical structures of the elbow and 12 smaller reference elements (2
      anatomical variants, 4 ligaments, 3 nerves and 3 arteries) describing their MR
      appearance and pointing out the most effective planes for their representation.
      Finally, the image quality of the knee coil was compared with that of the
      shoulder coil. RESULTS: All bones were clearly depicted on the coronal and axial
      planes, while the semilunar groove and its anatomical variants were best seen on
      the sagittal plane. The joint cartilage was best depicted on the coronal plane
      with T2-weighted GE sequences. Collateral ligaments were best seen with the elbow
      extended and the forearm supine (knee coil), on coronal T1-weighted SE images,
      where the radial and ulnar collateral ligaments were visible in 71.4% and 85.7%
      of the subjects, respectively. Annular ligaments, muscles and tendons were best
      demonstrated on the axial plane with the elbow extended and the forearm supine
      (knee coil), while the triceps tendon was best recognized on the sagittal plane
      with the elbow flexed and the forearm prone (shoulder coil). Vessels and nerves
      were also best seen on the axial plane with the elbow extended and the forearm
      supine; in particular, the median nerve was visible in 71.4% of the subjects.
      DISCUSSION AND CONCLUSION: MRI is very effective in representing elbow anatomical
      structures. Its accuracy depends on elbow (flexed or extended) and forearm (prone
      or supine) position. The coronal images with the elbow extended and the forearm
      supine (knee coil) are the most effective to show the ligaments and the joint
      surfaces between the radial head and the coronoid process of ulna with the
      capitellum and trochlea of distal humerus, while the axial images best depicted
      the muscles, vessels and nerves. The coronal and axial planes, with the elbow
      flexed and the forearm prone (shoulder coil) are poorly effective for anatomical
      detailing, even though this position is more comfortable for the patient, while
      the sagittal plane is best suited to depict the triceps tendon. This position may
      be used when the elbow cannot be fully extended or when the triceps tendon is
      studied.

PMID- 9636721
TI  - Diagnostic imaging of the early slipped capital femoral epiphysis.
AB  - INTRODUCTION: Early slipped capital femoral epiphysis (ESCFE) can be treated
      surgically, with excellent results, if it is diagnosed in its initial stage;
      however, the rate of late or missed diagnoses remains surprisingly high. PURPOSE:
      We compared radiography, US and MR sensitivity in ESCFE diagnosis. MATERIAL AND
      METHODS: We examined 21 symptomatic overweight patients (15 boys and 6 girls)
      aged 9 to 15 years with anteroposterior radiographs; frog leg images were not
      acquired in 3 cases only. US was performed in 19 cases and the images acquired
      with 5-7.5 MHz probes on the sagittal plane parallel to the femoral neck. MRI was
      performed in 9 cases, with coronal and sagittal T1 SE and T2* GE images. RESULTS:
      Our sensitivity rates were 66% for anteroposterior radiography (6 false
      negatives), 80% for combined anteroposterior and frog leg images (3 false
      negatives), 95% for US (1 false negative) and 88% for MRI (1 false negative).
      DISCUSSION AND CONCLUSION: We believe that US is the method of choice in ESCFE
      diagnosis; if it is negative, but pain persists, MRI should be performed.

PMID- 9636722
TI  - [Ozone therapy in lumbar sciatic pain].
AB  - INTRODUCTION: Medical ozone is a mixture of oxygen and ozone which can be used
      for several medical applications. Ozone was first applied clinically to the
      treatment of lumbar sciatic pain peridurally, while Pietrogrande was the first in
      Italy to report on its intradiscal administration to treat nucleus polposus
      herniation. On account of these considerations, we have decided to introduce this
      method in our Institute (I.C.O.T. Latina) as an alternative to surgery in the
      treatment of lumbar sciatic pain supported by an intradiscal hernia. MATERIAL AND
      METHODS: September, 1995, to April, 1997, we treated more than 1000 patients with
      intradiscal ozone infiltration. We prospectively analyzed the first 50 patients,
      with 6 months' follow-up at least; all of them were preliminarily submitted to
      clinical examination, electromyography, CT and MRI. After local anesthesia, we
      injected the disk, with 18-20 G needles and under CT or fluoroscopic guidance,
      with 12 ml of a mixture of oxygen and ozone at a concentration of 20-30
      micrograms/ml. The treatment was repeated two or three more times at intervals of
      3, 15 or, when necessary, 30 days. After each treatment, CT follow-ups were
      carried out and the final follow-up was made 3 months later. RESULTS: We divided
      our results into clinical and instrumental. As for clinical response, we had 68%
      positive results (40% excellent, 28% good) and 32% negative results (10% of
      patients underwent surgery and 22 are under medical and physical treatment). As
      for CT response, we had 82% positive results (36% excellent, 46% good), while no
      major changes between pre- and post-treatment CT findings in the remaining 18% of
      cases. CONCLUSIONS: Ozone therapy, thanks to its ease of execution and
      noninvasiveness, permits the successful outpatient treatment of lumbar sciatic
      pain. Moreover, the lack of major complications and the good results obtained
      compared to other methods, such as chemonucleolysis, percutaneous automated
      discectomy, microsurgery and conventional surgery, suggest that ozone therapy can
      be considered the treatment of choice for lumbar sciatic pain and a valid
      alternative to surgery in many cases.

PMID- 9636723
TI  - [Digital panoramic radiography in patients with rigid internal fixations devices
      after maxillofacial surgery].
AB  - INTRODUCTION: Digital techniques have found promising applications in dental
      radiology in the recent past, namely with radiovisiography and digital panoramic
      radiography. These images present some features making them particularly
      interesting for alveolar bone studies. MATERIAL AND METHODS: Digital panoramic
      radiography with light-emitting phosphors was performed on 16 patients during
      postoperative follow-up. The patients were previously submitted to multiple
      maxillofacial osteosynthesis with rigid internal fixation devices (32 miniplates,
      12 microplates, 14 screws). Digital images were always observed and printed with
      analogic-like and Xeroradiographic-like post-processing. RESULTS: Digital
      panoramic radiographs yielded clear and effective images of the maxillary and
      mandibular arches and of surgical osteosynthesis, as demonstrated by a
      retrospective evaluation performed by three independent observers on a blind
      basis (score 3: 60.42%), with no major interobserver differences (p = .7286).
      Xeroradiographic-like images were the most effective in depicting bone structures
      and osteosynthesis materials, thanks to their better detailing and typically
      lower overall contrast. Among the drawbacks of the digital technique, reduced
      cassette size may prevent the full view of the mandibular arch from the symphysis
      to both condylar regions. The edge effect, which is typical of Xeroradiographic
      images, may mask useful details within the trabecular bone close to metal
      implants. This effect was present in some of our cases, but it was seldom
      disturbing according to our retrospective evaluation (score 3: 53.40%), with good
      interobserver agreement (p = .1117). CONCLUSION: Digital panoramic radiography
      proves to be a useful tool to study metal implants after maxillofacial surgery as
      well as alveolar bone structure. The digital technique markedly reduces the
      radiation dose to the patient, which is very important for an X-ray examination
      that must be repeated several times, often in young subjects.

PMID- 9636724
TI  - [Non-palpable lesions of the breast. Retrospective analysis of mammographic and
      ultrasonographic indications for surgery].
AB  - INTRODUCTION: The differential diagnosis of malignancy in small foci of
      microcalcifications or in extremely small nodes can be difficult. We carried out
      a retrospective analysis of integrated mammographic and US results, correlated
      with histologic data, to assess the limitations of each method and to optimize
      and benign/malignant ratio. MATERIALS AND METHODS: Our series consisted of 485
      nonpalpable breast lesions submitted to histologic examination after vegetable
      charcoal marking. We gave each lesion an 0-5 score according to the degree of
      diagnostic doubt/suspicion after mammography and US, which results were
      correlated with histologic data to assess the carcinoma frequency in the various
      groups identified. RESULTS: The analysis of mammographic and US images showed
      that the most frequent mammographic alteration in the lesions submitted to biopsy
      was an isolated cluster of microcalcifications (40.99%): of these, 36.86% were
      neoplastic. The nodules submitted to biopsy, which were 29.81% of the total,
      showed a cancer rate (36.80%) very similar to that of the microcalcifications.
      The carcinoma rate rose to 37.93% when the microcalcifications were associated
      with nodes. The highest carcinoma rates, i.e., 52.94% and 66.66%, respectively,
      were found in parenchymal distortions, either isolated or associated with
      microcalcifications, which however were only 7.03% and 3.10%, respectively, of
      the total number of cases. DISCUSSION AND CONCLUSIONS: Our study showed that: 1)
      a highly suspicious US result must be seriously considered when a negative
      mammography has poor intrinsic contrast; 2) a highly suspicious US image with a
      little suspicious good contrast mammography requires further confirmation before
      surgery is planned; 3) when the mammographic finding is mid-to-highly suspicious,
      further investigations are needed even if US is negative. To conclude, even
      though the histologic examination of nonpalpable breast lesions involves
      performing a biopsy, we believe this is acceptable when performed on an
      outpatient basis, under local anesthesia and removing a limited amount of tissue
      only. The benign/malignant ratio ranges 2 to 1.5: if it is further reduced (below
      1.5), there will be the risk of missing some early neoplastic lesions.

PMID- 9636725
TI  - [Role of diagnostic imaging of the breast in patients treated with postsurgical
      radiotherapy or presurgical radiotherapy or chemotherapy].
AB  - INTRODUCTION: In the last 25 years, random trials on the advantages of combined
      surgery and irradiation/chemotherapy of breast cancer demonstrated similar
      survival rates to those of massive surgery. However, both irradiation and
      chemotherapy have advanced and now yield good local control of the disease, so
      that even large breast cancers can be made operable. Breast cancer follow-up is
      carried out with imaging and clinical examinations to detect early locoregional
      recurrences, contralateral lesions and distant recurrences: to this purpose, we
      carried out a comparative study of all imaging modalities. MATERIAL AND METHODS:
      We retrospectively reviewed the data of 42 breast cancer (T2-T3 N0-N+) patients
      of the Senology Center of the Catholic University (Rome, Italy) treated with
      irradiation and/or chemotherapy for tumor debulking to permit conservative
      surgery. We investigated the sensitivity and the indications of mammography, B
      mode and color Doppler US and MRI in measuring the exact tumor size and detecting
      locoregional metastatic nodes. RESULTS: After 3 years' treatment, our recurrence
      rate (19%) is a little higher than those in the major international trials (4.2
      9% and 5 tears). The recurrence was on the surgical scar in 75% of cases (6/8),
      while multifocal tumors were found in 25% of cases. US was the most accurate
      method in measuring tumor size in 90% of cases (18/20), while mammography
      frequently overstaged the lesion and yielded exact measurements in 65% of cases
      (13/20). MRI was as accurate as US, but this technique is too expensive and
      little available in Italy. US accurately diagnosed lymph node recurrences (70%
      sensitivity), but MR rate was even higher (80%), while mammography and color
      Doppler US had only 5-10%. As for treatment outcome, an irregular and blurred
      nodule or multifocal lesions at mammography indicate poor/no response, while a
      much smaller radial scar than at previous similar follow-ups indicates treatment
      success. CONCLUSIONS: When correctly integrated, mammographic, US and MR patterns
      permit exact tumor size measurement and show possible locoregional lymph node
      involvement in the patients submitted to conservative surgery and
      irradiation/chemotherapy. In contrast, color Doppler findings remain poorly
      specific in this disease, with about 55% sensitivity. Therefore, radiologic
      studies, with clinical and laboratory data, have a major prognostic value in
      assessing the biological response to combined treatment.

PMID- 9636726
TI  - [Clinico-radiologic problems in the study of the male breast in gynecomastia].
AB  - INTRODUCTION: Gynecomasty is usually classified as normal of abnormal, except for
      25% of cases which are classified as idiopathic because their causes and
      pathogenesis remain unknown. Gynecomasty is diagnosed mainly on clinical grounds,
      while integrated imaging, sometimes combined with cytology, is used to
      distinguish benign from malignant forms. Bilateral gynecomasty is easy to
      diagnose, especially when patients report assuming particular drugs or present
      other risk factors, but unilateral or asymmetrical gynecomasty is a diagnostic
      problem. Primary male breast cancer usually presents as a unilateral hard mass,
      often infiltrating the dermis and with early lymph node metastases; it is
      associated with gynecomasty in 20% of cases. MATERIAL AND METHODS: We examined 76
      men (age range, 15-75 years) referred for breast enlargement; the patients with
      radiologic findings of breast adiposis were not included in our series. All
      patients were submitted to standard projection mammography with a high resolution
      dedicated film and to real time US with high frequency probes (7.5-12 MHz).
      RESULTS: Breast enlargement was unilateral in 48% of cases and bilateral in 52%.
      The radiologic patterns, compared with histologic or clinical-therapeutic follow
      up, permitted the correct diagnosis in 72 of 76 patients (94%). The extant four
      patients had chronic inflammation (3 cases) and a malignant tumor with
      questionable imaging features. Overall imaging findings were: 55 cases (72%) of
      actual gynecomasty--unilateral in 17 and bilateral in 38 cases--9 unilateral
      malignant tumors (12%), eleven cases of inflammation (14%) and 1 case (2%) of
      unilateral metastasis from plasmocytoma. Sixteen (29%) actual gynecomasty
      patients (21% of the whole series) had a nodular form (unilateral in 6 and
      bilateral in 10 cases), 23 (42% and 30% of the whole series) had a dendritic form
      (unilateral in 7 and bilateral in 16 cases) and 16 (29%, 21% of the whole series)
      had a glandular form. CONCLUSIONS: Diagnosing gynecomasty is relatively easy in
      the patients with bilateral forms with a positive history of associated exogenous
      or endogenous factors, while focal unilateral or asymmetrical forms are difficult
      to distinguish into benign and malignant. The radiologic pattern may be
      questionable especially in chronic inflammation and in some malignant forms and
      must therefore be integrated with cytologic or surgical findings.

PMID- 9636727
TI  - Hodgkin disease and non-Hodgkin lymphoma: plain chest radiographs and chest
      computed tomography of thoracic involvement in previously untreated patients.
AB  - PURPOSE: To provide further information about the presentation of thoracic
      involvement in Hodgkin disease and non-Hodgkin lymphoma and to compare chest
      radiography with chest CT findings. MATERIALS AND METHODS: We reviewed the chest
      radiographs and the CT images of 100 Hodgkin and 100 non-Hodgkin patients, all of
      them untreated. Our data were compared with those of literature series: the
      latest study comparing the different patterns of Hodgkin and non-Hodgkin disease
      appeared in 1976 and it compared chest radiography with conventional tomography,
      not with CT. RESULTS: Intrathoracic involvement (75% vs 48%) and adenopathy (74%
      vs 28%) were more frequent in Hodgkin than in non-Hodgkin lymphoma. Ninety-nine
      per cent of the patients with intrathoracic involvement (74/75) had nodal
      disease. Paratracheal/prevascular nodes were most frequently involved, namely in
      72/74 Hodgkin (97%) and in 27/28 non-Hodgkin patients (96%). The lung parenchyma
      was more often involved in non-Hodgkin (24%) than in Hodgkin (8%) patients; it
      was associated with mediastinal/hilar adenopathy in all Hodgkin and in 10/24
      (42%) non-Hodgkin cases. Parenchymal involvement was demonstrated with chest
      radiography in 7/8 Hodgkin (88%) and in 13/24 non-Hodgkin patients (54%). Chest
      radiography showed paratracheal/prevascular adenopathy more often in Hodgkin
      (54/72, 75%) than in non-Hodgkin (15/27, 56%) cases. Subcarinal and internal
      mammary adenopathy was poorly depicted with plain films, while hilar adenopathy
      was generally identified with both CT and chest radiography. Chest radiography
      usually missed posterior mediastinal and anterior diaphragmatic adenopathy.
      CONCLUSIONS: The differences in the presentation of Hodgkin vs non-Hodgkin
      disease are not sufficiently distinctive to permit radiographic differentiation
      of the two conditions, but some patterns are helpful. Recognizing the frequency
      of thoracic involvement and that of the additional CT findings in Hodgkin and non
      Hodgkin patients makes a sound basis for lymphoma imaging.

PMID- 9636729
TI  - [Diagnostic imaging of splenic cysts in children].
AB  - INTRODUCTION: Nonparasitic splenic cysts are a rare finding: they can be
      distinguished into true cysts (epidermoid or epithelial) cysts or false
      (pseudocysts), depending on the presence/absence of an inner epithelial lining.
      They are usually found during the second and third decade of life, although they
      can also appear during childhood. They grow bigger in children, becoming
      clinically apparent due to the symptoms of compression of adjacent structures.
      The diagnosis is radiological, made with ultrasonography (US) and computed
      tomography (CT). We report the US and CT patterns of splenic cysts to
      differentiate true from false cysts. MATERIAL AND METHODS: Our series consists of
      5 patients, aged 5-17 years, all examined with US and CT; one of them was also
      submitted to plain abdominal radiography. Conventional CT was used in 2 cases and
      helical CT in the extant 3. RESULTS: All examinations yielded useful clinical
      informations. The only radiograph showed the rightward displacement of the
      gastric gas bubble US always identified the cyst and its pertinence to splenic
      parenchyma, although failing to assess the liquid/solid nature of a highly
      echogenic cyst in one case. CT confirmed the cystic nature of all masses and
      showed the lack of contrast enhancement of cyst walls and the presence of septa
      or parietal calcifications. DISCUSSION: Radiological examinations, particularly
      US and CT, can diagnose splenic cysts unquestionably, correctly defining the
      relationships with adjacent organs. CT is more sensitive than US in detecting
      septa or calcifications, which are definitely useful findings to distinguish true
      from false cysts, since internal septa are more frequent in true cysts while
      parietal calcifications are typical of pseudocysts. The final diagnosis, however,
      is made at histology.

PMID- 9636728
TI  - [Magnetic resonance angiography of coronary arteries: assessment in patients with
      coronary stenosis and control after stent positioning].
AB  - INTRODUCTION: Cardiovascular disease remains the leading cause of death in the
      world. Invasive coronary angiography is currently the only clinical method
      available to visualize the coronary arteries, with up to 20% of the procedures
      demonstrating no evidence of severe coronary artery stenoses. We investigated the
      role of two-dimensional (2D) coronary magnetic resonance angiography (MRA) in
      patients with suspected coronary arteries disease and to check the placement and
      the patency of previously placed coronary artery stents. MATERIAL AND METHODS:
      Eleven patients with suspected coronary artery disease who underwent elective
      cardiac catheterization with coronary angiography were examined with 2D coronary
      MRA to detect coronary artery stenoses. Other 11 patients with 13 stented
      coronary arteries (6 RCA, 5 LAD, 2 Lcx) were prospectively examined with MRA one
      day to 8 months after stent placement. Eighteen amagnetic stents were imaged.
      Imaging was performed with a 1.5 T MR unit (GE Signa Horizon Echo Speed) with a
      phased array multicoil. Segmented k-space fast GE sequences were acquired with
      and without fat suppression at several cardiac cycle phases within a single
      breath-hold. Correlation with coronary angiography was performed in all patients.
      RESULTS: Thirteen significant stenoses were found at coronary angiography in 11
      coronary arteries. The sensitivity and specificity of MR coronary angiography, as
      compared with conventional angiography, in correctly identifying the single
      vessels with > 50% angiographic stenoses were 73% and 94%, respectively. The
      corresponding positive and negative predictive values and accuracy were 88%; 84%
      and 86%, respectively. As far as the study of coronary artery stents is
      concerned, no MR-related adverse events were observed. The stents were visualized
      as signal loss areas. The length of the signal loss corresponded to the length of
      the stents in all 18 cases (r = 97). The patent blood flow distal to the stents
      appeared as a high-signal band distal to the signal void, corresponding to stent
      patency at coronary angiography. CONCLUSIONS: Although in an early stage of
      technical development, 2D coronary MRA can depict 73% of hemodynamically severe
      coronary artery stenoses. Moreover breath-hold coronary cine MRA is a safe
      technique to visualize coronary artery stents. Stent site and patency can be
      noninvasively studied with this technique.

PMID- 9636730
TI  - [Biliary complications of liver transplant. Role of cholangiography with magnetic
      resonance].
AB  - INTRODUCTION: Orthotopic liver transplantation is considered the treatment of
      choice in several hepatic conditions. The five-year patient survival rate is
      approximately 75%, thanks to progress in both surgical techniques and
      postoperative medical treatment. Biliary complications are one of the commonest
      causes of failure and their prompt identification is difficult due to their
      insidious clinical pattern and to the poor predictive value of a negative US
      examination. To date, invasive contrast cholangiography (endoscopic retrograde
      cholangiography and percutaneous transhepatic cholangiography) may be the only
      way to identify anatomic abnormalities and it is therefore a necessary
      examination when biliary obstruction is suspected. The aim of our work was to
      assess the possible role of MR cholangiography in late biliary complications of
      liver transplanted patients. MATERIAL AND METHODS: Twenty-three liver transplant
      recipients (11 men and 12 women, mean age: 51.1 years) were submitted to MR
      cholanglography using non-breath-hold, fat-suppressed three-dimensional turbo
      spin echo sequences, (TR = 3000 ms, TE = 700 ms, ETL = 128). Our patients
      presented with clinical, laboratory and US patterns doubtful for biliary
      obstruction. The diagnostic confirmation was obtained at percutaneous
      transhepatic cholangiography (four cases), endoscopic retrograde cholangiography
      (eight cases), T-tube cholangiography (one case) or clinical follow-up (ten
      cases). RESULTS: No biliary tract abnormalities were detected at MR
      cholangiography in 11 cases. Twelve strictures were diagnosed in eleven patients
      (9 anastomotic, two nonanastomotic/intrahepatic and one
      nonanastomotic/extrahepatic, with associated anastomotic and nonanastomotic
      strictures in two cases). MR cholangiography correctly defined the stricture site
      and the dilation of the bile ducts above in all cases, with optimal correlation
      with contrast cholangiographic findings. The common bile duct below the stricture
      was visible in 9 of 10 patients with extrahepatic strictures on MR
      cholangiography and in 8 of 10 patients on contrast cholangiograms. The distal
      common bile duct was missed on both MR cholangiography and diagnostic
      percutaneous transhepatic cholangiography in a patient only. The strictures were
      correctly graded in 8 of 10 patients, with two cases of overestimation. Other
      findings were a 1-cm stone proximal to the obstructed common bile duct, multiple
      intrahepatic stones in another case and common bile duct kinking at the
      anastomosis. CONCLUSIONS: MR cholangiography is a useful imaging method in the
      follow-up of liver transplant recipients which can assess the biliary obstruction
      and therefore permit to limit the use of invasive procedure only for
      interventional purposes.

PMID- 9636731
TI  - [Morpho-functional study of the kidney in patients with kidney disease and liver
      disease with magnetic resonance].
AB  - INTRODUCTION: We studied renal function and perfusion after the i.v. injection of
      Gd-DTPA-BMA, a nonionic paramagnetic contrast agent, to assess renal morphology
      and function in normal subjects, in renal insufficiency patients and in patients
      with hepatic failure and normal renal function. The latter were chosen because
      some patients with advanced hepatic failure may suffer from the hepatorenal
      syndrome, characterized by severe vasoconstriction in the renal cortical vessels.
      We investigated if dynamic MRI can detect early renal perfusion abnormalities in
      the patients who will eventually develop this syndrome. MATERIAL AND METHODS:
      Thirty MR examinations were carried out on 30 subjects after the i.v. injection
      of Gd-DTPA-BMA. Our series consisted of: 10 normal subjects; 10 renal
      insufficiency patients; 10 patients with hepatic failure and normal renal
      function. MR examinations were performed on a Philips ACS II scanner operating at
      1.5 T. Two sequences were carried out in all cases: T1-weighted SE and T1
      weighted TGE sequences after the bolus injection of .1 mmol/kg contrast agent.
      Renal longitudinal diameter and parenchymal thickness were measured in all cases
      and signal intensity time curves were always made. The signal intensity of the
      cortex, corticomedullary junction, medulla and pyelocaliceal system of each
      kidney was measured using a region of interest (ROI). The signal intensity curves
      were made considering quantitative parameters, including the area below the curve
      (ASC), the peak (P) and the time to peak (T-P). RESULTS: Longitudinal diameter
      and parenchymal thickness values were significantly lower in renal insufficiency
      patients than in normal subjects. Four phases were demonstrated after i.v.
      contrast agent injection in normal subjects, namely A) the cortical phase, B) the
      corticomedullary junction phase, C) the medullary phase, D) the pyelocaliceal
      phase. No signal intensity decrease in the medullary and pyelocaliceal curves was
      observed in renal insufficiency patients. Signal intensity curves values were
      lower in hepatic failure patients than in those with normal renal function.
      Hepatic failure patients could be divided into two groups: 5 patients had low P
      and ASC values and 4 had normal P and ASC values. The patients with lower P and
      ASC values developed the hepatorenal syndrome within a few months of the MR
      examination. DISCUSSION: Signal intensity decreased in the pyelocaliceal system
      phase in normal subjects because of the high paramagnetic contrast agent
      concentration. The lack of signal intensity decrease in renal insufficiency
      patients was caused by the reduced capability of concentrating Gd-DTPA-BMA. Lower
      signal intensity values in hepatic failure patients may be considered an early
      sign of the hepatorenal syndrome.

PMID- 9636732
TI  - ["Freddy frog" projection of the thorax: clinical applications in pediatric
      oncohematology].

PMID- 9636733
TI  - [Adjuvant radio-chemotherapy in cancer of the rectum treated with radical surgery
      and with high risk of recurrence. Preliminary results of a prospective study].
AB  - INTRODUCTION MATERIAL AND METHODS: From January, 1990, to December, 1995, 138
      consecutive patients with radically resected stage II and III rectal and
      rectosigmoid cancers were treated with adjuvant radiochemotherapy. Eighty-one
      patients with 24 months' follow-up were assessable. Low anterior resection (LAR)
      was performed in 64 (79%) patients and abdominoperineal resection (APR) in 17
      (21%). Twentynine (36%) stage II and 52 (64%) stage III patients entered the
      study. Within 45-60 days from surgery all patients received 5-Fluorouracil
      chemotherapy at the dose of 500 mg/m2/iv/d 1-5, every 4 weeks, for six cycles.
      Chemotherapy cycles 3 and 4 were administered at the same daily dose on
      radiotherapy days 1-3 and 29-31. Radiotherapy total dose consisted of 45 Gy/1.8
      Gy/day administered in 5 weeks with 18 MV photon beam to the pelvis with the four
      field "box" technique. Perineal scar was encompassed only after APR. A boost dose
      of 5.4 Gy to the tumor bed was given in 3 fractions of 1.8 Gy. Median follow-up
      was 37 months (range: 24-74 months). RESULTS AND DISCUSSION: Overall recurrent
      disease was reported in 28 of 81 patients (34%): local, systemic and both local
      and systemic relapses in 9 (11%), 14 (17%) and 5 (6%) cases, respectively.
      According to local extension, recurrence rates were 10% and 48% in stages II and
      III, respectively. Five-year overall and disease-free actuarial survivals were
      64% and 61%, respectively. Median time to relapse was 15 months (range: 7-43
      months). Significant prognostic factors for better tumor control were: stage (II
      vs III), disease site (proximal vs distal rectum), the surgical procedure (LAR vs
      APR), the number of involved nodes (< or = 4 vs > 4) and no extracapsular node
      invasion. The recommended dose of combined radiochemotherapy regimen used in this
      trial was generally well tolerated. The incidence of any grade > or = 3 acute
      toxicity (according to WHO grading) was 20% diarrhea, 6% tenesmus and 4%
      myelosuppression. Five (6%) patients had cronic diarrhea and other 3 (4%)
      radiotherapy-related severe late toxicity which required surgery. CONCLUSIONS:
      This study seems to provide similar survival and recurrence notes to other radio
      chemotherapy regimens published in the literature. However, a more aggressive
      approach is warranted in stage III patients considering the low 5-year survival
      recorded.

PMID- 9636734
TI  - [Assessment of radiation dose to patients in hysterosalpingography].
AB  - INTRODUCTION: The optimization principle applied to the patient radioprotection,
      recently introduced in Italian legislation, requires a careful analysis of the
      working procedures and clinical protocols generally used in radiological
      practice, to avoid unnecessary exposures with no loss in diagnostic information.
      We carried out this analysis in hysterosalpingography, which is the radiological
      examination usually performed on fertile women to detect uterine and tubal
      conditions. MATERIALS AND METHODS: The dosimetric survey was carried out on 35
      patients, 22 to 40 years old, to evaluate: a) entrance dose and dose x area
      product; b) doses to the most irradiated organs, that is ovaries and uterus; c)
      effective dose equivalent and effective dose. The doses were measured with LiF
      thermoluminescent dosimeters, while an ionization chamber enabled us to the
      calculate dose area product. Ovaries and uterus doses were calculated with a
      Monte Carlo program using skin entrance exposure data and some technical
      parameters of the examination. RESULTS: The good agreement of the results
      obtained with both dosimetric methods demonstrated their equivalence in this
      specific case where the use of a clinical protocol, with no lateral projection,
      made the dosimeters lie always within the X-ray beam. DISCUSSION AND CONCLUSIONS:
      The mean dose was 4.5 mGy for the ovaries and 6.2 mGy for the uterus. Following
      the recommendations of the International Commission on Radiological Protection,
      both effective dose equivalent, with a mean value of 2.0 mSv, and effective dose,
      with a mean value of 1.95 mSv, were estimated. In conclusion, our results show
      that the patient dose can be reduced by limiting the use of fluoroscopy, using
      small size films and decreasing the number of exposures.

PMID- 9636735
TI  - [Positron-emission tomography with fluorine-18-deoxyglucose in the staging and
      control of patients with lymphoma. Comparison with clinico-radiologic
      assessment].
AB  - INTRODUCTION: The clinical applications of fluorine-18-deoxyglucose Positron
      Emission Tomography (FDG PET) have been proposed on account of experimental
      evidence of increased glucose metabolism in tumor cells. MATERIAL AND METHODS: We
      examined 98 lymphoma patients--33 with Hodgkin and 65 with non-Hodgkin disease-
      with FDG PET and compared its findings with those of clinical and conventional
      radiologic studies. FDG PET was also used to follow-up 32 patients and the
      results were once again compared with clinical and radiologic data. RESULTS:
      During staging, 138 lesions were found, 82 of them (59%) in nodal and 56 (41%) in
      extranodal locations. Extranodal tumor sites were found in 39 patients (40%),
      namely 4 with Hodgkin (12%) and 35 with non-Hodgkin (54%) disease. FDG PET
      findings were in agreement with clinical and radiologic results in all nodal and
      extranodal lesions, since all of them exhibited abnormally increased FDG uptake.
      PET detected new tumor sites in 6 patients. In the follow-up, agreement was
      observed in the majority (78%) of lesions, 30 of them in complete regression, 15
      in partial regression and 17 in progression; however, the diagnostic results were
      in disagreement in the remaining (22%) tumor sites: no abnormal FDG uptake was
      found in 9 cases despite the persistence of radiologic abnormalities (post
      treatment fibrosclerosis). Slightly increased FDG uptake (residual disease) was
      found in the other 8 lesions, where there was no clinical and/or radiologic
      evidence of disease. CONCLUSIONS: FDG PET is a functional imaging technique
      useful to diagnose lymphomas and providing metabolic characterization of cancer
      abnormalities. Whole body PET permits the simultaneous assessment of nodal and
      extranodal lymphoma localizations. During the follow-up, FDG PET permits better
      monitoring of treatment effects than clinical and radiologic examinations.

PMID- 9636737
TI  - [Plexiform schwannomatosis of the tibial nerve: study with MR and surgical
      findings in a case].

PMID- 9636736
TI  - [Posterior synovial ganglion with compression of the supraspinatus nerve,
      infrequent cause of shoulder pain. Report of a case].

PMID- 9636738
TI  - [Congenital hemangiopericytoma of the neck: ultrasonographic findings and with
      MR].

PMID- 9636739
TI  - [Fibroadenoma and carcinoma of the breast. Clinico-radiological considerations in
      4 cases].

PMID- 9636740
TI  - [Contribution of computerized tomography in the diagnosis of left extrapleural
      hematoma secondary to spontaneous rupture of the thoraco- abdominal aorta. Report
      of a case].

PMID- 9636741
TI  - [Thrombophlebitis of the cavernous sinus. Magnetic resonance features in 2
      cases].

PMID- 9636742
TI  - [Splenic hemangiopericytoma: features with computerized tomography in 2 cases].

PMID- 9636743
TI  - Torsion of a wandering spleen. Radiologic assessment in one case.

PMID- 9636744
TI  - [Ultrasonographic diagnosis of gallbladder perforation caused by blunt abdominal
      injury. Report of a case].

PMID- 9636745
TI  - [Nephrocalcinosis caused by prolonged treatment with furosemide].

PMID- 9636746
TI  - [Comments on the good topical usage of non-steroidal anti-inflammatory agents].

PMID- 9636747
TI  - [Focus on bovine products].

PMID- 9636748
TI  - [Histopathology of exogenous and idiopathic lucites and provocation phototests].
AB  - OBJECTIVE: Provocative phototests are used regularly to explore photobiology in
      patients with photodermatoses. Our objective was to determine the reliability of
      the phototest in the diagnosis of idiopathic and exogenous light eruption in
      order to identify the ideal date for the histological examination by correlation
      between the histological aspects of light- triggered and spontaneous lesions.
      PATIENTS AND METHODS: Among 66 patients, there were 48 with polymorphous light
      eruptions, 13 with exogenous eruptions and 5 with chronic actinodermatitis. The
      histological findings of the provocative phototests were correlated with the
      clinical aspect, the date of biopsy and the histological aspect of the
      spontaneous lesions. RESULTS: In polymorphous light eruptions (48 cases) this
      test triggered a photoallergic reaction in 48% of the patients. There was a good
      correlation between the histological findings and clinical features in 96% of the
      cases. The histological image of the light-triggered lesion on day 6 was the
      closest to that of the spontaneous lesion. In exogenous eruptions and chronic
      actinodermatitis (18 cases), only 33% of the clinically positive phototests were
      also positive at histological examination. The histological image was the same
      for the provocative tests whether they were clinically positive or negative, with
      signs of epidermal phototoxicity, regeneration acanthosis and moderate
      perivascular lymphocyte infiltration of the superficial dermal layer.
      CONCLUSIONS: Our findings confirmed that the phototest provides a good
      correlation between histological findings and clinical presentation in idiopathic
      polymorphous light eruptions, justifying simple clinical interpretation, but did
      not demonstrate a rate of positive results as high as reported in the literature.
      Day 6 is the ideal date for a phototest biopsy. In exogenous light eruptions, the
      phototest is less reliable since the correlation between histology and clinical
      presentation is weaker. It is difficult to reproduce spontaneous lesions with the
      phototest, but if used, the phototest biopsy should be done on day 18.

PMID- 9636749
TI  - [Prognostic factors and predictive signs of malignancy in adult dermatomyositis].
AB  - INTRODUCTION: Prognosis in dermatomyositis is severe, partly due to the
      development of cancer. The aim of this study was to identify factors predicting
      cancer development and assess factors predicting reduced survival rate. PATIENTS
      AND METHODS: A retrospective analysis of 32 cases of dermatomyositis diagnosed on
      the basis of the Bohan and Peter criteria was performed. Diagnosis was certain in
      7 cases, probable in 13 and possible in 5. There were thus 7 cases of pure
      cutaneous dermatomyositis. Clinical and laboratory data were compared between
      patients with and without cancer and between deceased and surviving patients.
      RESULTS: Overall mortality was 37.5% at 4 years, confirming the gravity of
      dermatomyositis. Malignancy developed in 9 patients (28.1%) leading to death in
      all cases, within 18 months in 8. Amyopathic dermatomyositis was observed in 2 of
      these patients. Necrotic skin ulcerations (p < 0.01) and pruritus (p < 0.05) were
      significant predictive factors for the development of cancer. Poor prognosis
      factors were malignancy (p < 0.001), necrotic skin ulcerations (p < 0.01), and
      pruritus (p < 0.05). CONCLUSION: Prognosis is poor in certain sub-groups of
      patients with dermatomyositis. Such patients can be identified on the basis of
      skin lesions, notable necrotic ulcerations.

PMID- 9636750
TI  - [Atrophic collodion-like skin in long-term treatments with hydroxyurea].
AB  - INTRODUCTION: Despite good general and hematological tolerance, hydroxyurea
      frequently causes polymorphous skin lesions when given as long-term therapy.
      Distal skin atrophy, pseudodermatomyositis, pseudolichen and ulcerations have
      been observed. CASE REPORT: We report three cases of diffuse atrophic collodion
      skin in patients given long-term hydroxyurea. Histology findings demonstrated
      atrophy and the same signs located at the dermo-epidermal junction as seen in
      acute toxidermia due to hydroxyurea. Examination of the ultrastructure showed
      abnormalities in the proliferative epidermal layer which was disrupted by edema
      and a multiple, irregular basal membrane. DISCUSSION: The chronology of the
      lesions and partial resolution after treatment withdrawal together with clinical
      and histological signs demonstrating hydroxyurea impregnation would implicate
      hydroxyurea as the cause of this case of diffuse atrophic collodion skin. Cells
      in the epidermal layer of the skin, the most external layer in the organism, have
      a high turnover rate and would be more vulnerable to the cytostatic action of
      hydroxyurea than other tissues. The effect of hydroxyurea on keratinocytes
      implicated in the production and maintenance of the basal membrane would be one
      of the causes.

PMID- 9636751
TI  - [Malignant syphilis in human immunodeficiency virus infection].
AB  - INTRODUCTION: The associated infection with Treponema pallidum and human
      immunodeficiency virus (HIV) was responsible for the return of malignant
      syphilis. CASE REPORT: We report a case of malignant syphilis which revealed a
      HIV seropositivity. The lesions were typical. Serological features were in
      accordance with the diagnosis. A treatment with penicillin was prescribed and
      there was no relapse after five years. DISCUSSION: The diagnosis of malignant
      syphilis in a HIV positive patient may be difficult. The course of the disease
      may be serious and a prolonged treatment with high doses of penicillin is often
      necessary. The occurrence of the malignant syphilis in HIV positive patients is
      not fortuitous and seems to be related to an abnormal immunity.

PMID- 9636752
TI  - [Ulcers of the tongue, pityriasis lichenoides and primary parvovirus B19
      infection].
AB  - INTRODUCTION: We report a case of parapsoriasis en gouttes (or pityriasis
      lichenoides) which presents two peculiarities. First, the patient had lingual
      ulcerations and second, the eruption appeared during a seroconversion for
      Parvovirus B19. OBSERVATION: A 25 old woman presented a first episode of
      characteristic parapsoriasis en gouttes associated with purpuric palmoplantar
      lesions and lingual ulcerations, reaching deep muscular in histology. DISCUSSION:
      This observation of parapsoriasis en gouttes, peculiar because of lingual
      ulcerations, is mostly interesting because of its association with a primo
      infection to Parvovirus B19. The receptor of the virus is localised on
      endothelial cells and that could explain purpuric lesions and ulcerations
      observed.

PMID- 9636753
TI  - [Cowden disease: treatment with acitretine].
AB  - INTRODUCTION: Cowden's disease is a rare hereditary skin disease which is
      important to recognize due to the risk of cancer. CASE REPORT: A 40-year-old man
      was hospitalized for psoriasis. He presented florid papillomatous lesions
      involving the lip and the buccal cavity, a thyroid adenoma and polyposis of the
      gut. The diagnosis of Cowden's disease was retained. Treatment with acitretin,
      0.75 mg/kg/d was initiated for the psoriatic lesions. Hypertrophic lesions of the
      lip and mouth regressed during treatment but reappeared when the drug dose was
      tapered of then withdrawn. The course of the polyposis was not verified.
      DISCUSSION: This case demonstrates the frequency of digestive tract involvement
      in Cowden's disease and the favorable, though transient, effect of oral retinoids
      on mucosal lesions in Cowden's disease.

PMID- 9636754
TI  - [Perforating necrobiosis lipoidica: 2 cases].
AB  - INTRODUCTION: Perforating necrobiosis lipoidica is a rare clinical form of
      necrobiosis lipoidica and is almost always associated with diabetes. Necrotized
      tissue is usually eliminated via transfollicular perforations. CASE REPORT: We
      report two cases of perforating necrobiosis lipoidica associated with type II
      diabetes mellitus. The characteristic clinical feature was the presence of
      keratotic plugs around the periphery of the lesions. Transfollicular perforation
      predominated in the first case. The second also presented epidermal perforation.
      DISCUSSION: There have been only 6 cases of perforating necrobiosis lipoidica in
      the literature. To our knowledge, this is the first case report of transepidermal
      elimination. We confirmed the constant association between this perforation type
      and diabetes mellitus.

PMID- 9636755
TI  - [A case for diagnosis: tuffed hair folliculitis].

PMID- 9636756
TI  - [A case for diagnosis: infantile digital fibromatosis].

PMID- 9636757
TI  - [Prurigo strophulus: cutaneous manifestation of hypersensitivity to environmental
      arthropods].

PMID- 9636758
TI  - [Bartonella infections].

PMID- 9636759
TI  - [Question of the month: should dermatologic check-up be done?].

PMID- 9636760
TI  - [What is a Caucasian?].

PMID- 9636761
TI  - [Melanoma in Togo. A retrospective study over 20 years].
AB  - INTRODUCTION: The malignant melanoma is a rare malignant tumour in black
      patients, but it is common in white patients. MATERIAL AND METHODS: Medical
      records were reviewed retrospectively during 20 years (1973-1992) to determine
      the epidemiological features of malignant melanoma in Togo. RESULTS: During this
      period 63 cases (31 males and 32 females) of malignant melanoma were
      histologically diagnosed; an average of 3.15 cases each year. The tumor takes
      place preferably on the feet 40 cases (63.49%), hands 15 cases (19.04%), legs and
      thigh 10 cases (15.87%). CONCLUSION: The results of this study confirm the
      particularity of malignant melanoma in black subjects: its rarity and the feet
      localizations.

PMID- 9636762
TI  - [Cutaneous immature hemangioma and hepatic angioma: there is no frequent
      association].
AB  - INTRODUCTION: The aim of this work was to determine the usefulness of systematic
      liver sonography in patients with immature cutaneous hemangiomas. PATIENTS AND
      METHODS: Children with immature cutaneous hemangiomas who met inclusion criteria
      underwent liver sonography. RESULTS: No case of hepatic angioma was observed.
      CONCLUSIONS: Liver sonography is not necessary as a routine test in children with
      several immature angiomas. This examination could be proposed in situations other
      than those evaluated in this work including miliary angiomas, unusual immature
      angiomas, hepatomegaly, unexplained heart failure.

PMID- 9636763
TI  - [Treatment of keloid with intralesional bleomycin].
AB  - INTRODUCTION: Treatment of keloids is often disappointing and sometime quite
      difficult to manage. In addition to unpleasant esthetic effects, treatment may
      also produce functional impairment due to pruritus and contraction of the scar
      tissue. PATIENTS AND METHODS: We proposed a new treatment scheme using
      intralesional infiltrations of bleomycin. RESULTS: We treated 31 keloids and 5
      hypertrophic scars with 3 to 5 infiltrations with a 1-month period. Total
      regression was obtained in 25 keloids and hypertrophic scars. Important
      regression was obtained in 6 keloids (86% good results). Treatment was effective
      in all cases within the first 2 infiltrations evidenced by a reduction in the
      volume of the keloid and clear reduction of functional impairment in most
      patients. CONCLUSION: Effective well-tolerated treatment without pain was
      achieved with infiltration suggesting that this treatment should be used as first
      line therapy for keloids.

PMID- 9636764
TI  - [Abnormal central nervous conduction in long-term treatments with retinoids].
AB  - INTRODUCTION: Neurological manifestations are uncommon among the undesirable
      effects of systemic retinoid therapy. We observed a case of axial rigidity
      imputable to acitretine. Somesthesic evoked potentials were also altered. We
      therefore searched for such abnormal findings in patients given long-term
      systemic retinoid therapy. PATIENTS AND METHODS: A neurological exploration was
      performed in two groups of patients, G1 and G2, with psoriasis and no
      neurological complaint. The exploration included a physical examination, a study
      of the somesthesic evoked potentials of all 4 limbs and an electromyogram in case
      of abnormal findings. There were 8 patients (3 women, 5 men, mean age 56 years,
      age range 39-71) in G1 treated with systemic retinoids for a mean 140 months (80
      185). Cumulative dose was 50 to 280 g with a daily dose of 0.2 to 0.6 mg/kg/day,
      i.e 20 to 50 mg/d of etretinate or acitretine. In G2, there were 5 subjects (mean
      age 42 years, range 21-52) with psoriasis (mean duration 20 years range 14-25)
      who had never been treated with systemic retinoids. RESULTS: Alterations in
      somesthesic evoked potentials were observed in 7 of the 8 patients in G1.
      Bilateral disturbances were seen in 6 cases, demonstrating abnormal lemniscal
      central nervous conduction in the dorsal and/or cervical level in 3 cases and the
      cervical level alone in 3 cases. There was one asymmetrical case involving the
      lumbar level on the right and the dorsal and/or cervical level on the right. Only
      one of the 5 controls in G2 had a minimal unilateral reduction in somesthesic
      evoked potentials involving the lower limb. Direct effect of systemic retinoids
      was retained in absence of any other cause due to metabolic, toxic or deficient
      disorders or spinal compression. CONCLUSION: Long-term use of systemic retinoids
      induces frequent latent neurological anomalies expressed as lemniscal central
      nervous conduction. It is hypothesized that pathogenesis involves changes in the
      lipid composition of the nervous membranes.

PMID- 9636765
TI  - [Anetoderma during antiphospholipid syndrome. 3 cases].
AB  - INTRODUCTION: Anetoderma is a skin disease of unknown etiology sometimes
      encountered in patients with a lupus syndrome. We report a clinical and pathology
      analysis of 3 selected cases of anetoderma associated with systemic lupus
      erythematosus and/or antiphospholipid syndrome. CASE REPORTS: Three patients had
      skin lesions typical of anetoderma. Antiphospholipid antibodies were present in
      all three (anticardiolipin in 3, circulating lupus anticoagulants in 3, anti-beta
      2GP1 in 2). One patient with systemic lupus erythematosus had signs of
      antiphospholipid syndrome, the two others had primary antiphospholipid syndrome.
      DISCUSSION: The analysis of our cases and a review of the literature suggest that
      anetoderma is a disease which develops in the immunological environment of lupus,
      and is apparently more related to the presence of antiphospholipids than lupus
      itself. Thus anetoderma could be another cutaneous sign of the antiphospholipid
      syndrome.

PMID- 9636766
TI  - [Acute necrotizing cutaneous streptococcal infection following bites or scratch
      by dog or cat].
AB  - INTRODUCTION: Domestic animal bites or scratches are quite frequent. Among banal
      bacteria isolated from infected bites or scratches, group A streptococcus seems
      to be frequently associated with severe infections. CASE REPORTS: Three cases of
      acute necrotizing cutaneous streptococcal infections, following cat or dog bite
      or scratch are reported. Twice, group A streptococcus was isolated from cutaneous
      swabs. In the third case, previous antibiotic therapy had sterilised
      bacteriological samples. Diagnosis was ascertained on the basis of clinical
      presentation and significant antistreptococcal antibodies elevation. Skin
      necrosis around the inoculation area was observed in the 3 cases. Cicatrisation
      required an average of two months under appropriate treatment. DISCUSSION: An
      evolution towards cutaneous necrosis localized to the initially injured area is
      common to these three cases. This peculiar evolution is worth to be known in
      order to choose an effective anti streptococcal antibiotherapy whenever domestic
      animals bites and scratches are to be treated.

PMID- 9636767
TI  - [Giant congenital blue nevus of the scalp].
AB  - INTRODUCTION: Blue nevi are small acquired melanocytic tumors. Two clinical forms
      are described, a fibrous form and a cellular form. Giant nevi are exceptional.
      CASE REPORT: We describe a patient with a giant blue nevus of the scalp. In
      addition to this congenital, noninvasive tumor the patient presented numerous
      cutaneous melanocytic nevi. The main lesion was removed by surgical exeresis
      followed later with reconstruction plasty. The histological examination of the
      surgical specimen showed an infiltrating blue cell nevi. After a 4-year follow
      up, there has been no recurrence and no metastasis. DISCUSSION: There have been
      11 cases of giant blue nevi reported in the literature. All were congenital
      lesions with polymorphous clinical and histological aspects. Fibrous forms are
      noninvasive and cellular forms have a potential for local invasion, whether
      shortly after birth or later with invasion of muscles, bone and meninges without
      intracerebral extension. Congenital blue nevi require early surgical exeresis.

PMID- 9636768
TI  - [Follicular basaloid hamartoma localized in the sacral region with papular plaque
      type].
AB  - INTRODUCTION: Basaloid follicular hamartoma is a benign tumor with superficial
      dermal proliferation of thin basaloid cords in a fibrous stroma. CASE REPORT: A
      congenital case with sacral plaque-like papules is described. DISCUSSION: Three
      different forms have been reported: a solitary form (usually an alopecic scalp
      plaque), a generalized acquired form associated with myasthenia, and a linear
      form. Histological diagnosis may be difficult and require clinico-pathological
      evaluation.

PMID- 9636769
TI  - [Benign symmetrical lipomatosis of the tongue].
AB  - INTRODUCTION: Lipomatosis of the tongue is rarely observed. CASE REPORT: An 85
      year-old man with chronic alcoholism presented several symmetrical lipomas of the
      tongue with no other clinical manifestations. There was no capsule at the
      histology examination. DISCUSSION: The multiple and symmetrical nature of the
      lesion without a capsule led to the diagnosis of benign symmetrical lipomatosis
      of the tongue, the fourth case reported in the literature.

PMID- 9636770
TI  - [Acne induced by amineptin: adnexal toxiderma].
AB  - INTRODUCTION: Amineptine-induced acne is a classical side effect often
      encountered after prolonged and excessive use of the antidepressor. CASE REPORT:
      We report the case of a young female drug addict (benzodiazepines and alcohol)
      who denied overuse of amineptine. The initial inflammatory aspect of the lesion
      was unusual as was the histology report. The sebaceous glands were the site of
      cystic dilatation as would be expected, but in addition the sudoriparous glands
      showed keratinizing syringometaplasia with areas of neutrophilic eccrine
      hidradenitis. DISCUSSION: This is the second report of such a case similar to
      other due to chemotherapy, benaxoprofene or toxic agents for example, and
      corresponds to direct toxicity to the sudoriparous glands which accumulate
      amineptine. We therefore propose the term of adnexal toxic drug eruption.

PMID- 9636771
TI  - [Cutaneous manifestations of acromegaly: 4 cases].
AB  - INTRODUCTION: Some skin changes in acromegaly belong to the classical dysmorphic
      syndrome. Furthermore, other minor skin changes can be associated. OBSERVATIONS:
      We report 3 patients consulting in the department of Dermatology for various skin
      changes that have lead to the diagnosis of acromegaly. However these patients
      have also typical dysmorphic syndrome that they have failed to recognize. The
      fourth patient associated a cutaneous mastocytosis and acromegaly, as reported
      only once in literature. The evolution of the minor skin changes was parallel
      with the endocrinopathy. Moreover in one case, they have preceded the recurrence
      of the acromegaly. COMMENTS: Our observations demonstrate the importance of the
      minor skin changes that lead the patient to consult more than the dysmorphic
      syndrome. Moreover these changes that depend of growth hormone and other
      associated growth factors can be evolutive signs for endocrinopathy.

PMID- 9636772
TI  - [Recurrent phototriggered summer light eruption of the axillary and inguinal
      area: an atypical topographic form of benign summer lucitis].
AB  - INTRODUCTION This case report of benign summer light eruption emphasizes the
      importance of phototests in the diagnosis of photosensitive dermatoses. CASE
      REPORT: A 25-year-old man, phototype II, had experienced a pruriginous
      papulovesicular erythematous eruption of the axillary and inguinal regions each
      summer for 12 years. A high-dose UV phototest (40 J/cm2 x 3 days) directed on the
      right posterior axillary area and a whole body exposure test (4 J/cm2 UVA, 20
      mJ/cm2 UVB x 3 days) were positive both clinically and histologically on day 4.
      DEM B was normal at 26 mJ/cm2. Iterative polychromatic phototest (DEM x 3 days)
      in the area usually involved (left posterior axillary region) was negative. The
      simple UVA (13 J/cm2) and iterative phototests performed on the back were
      negative. The results of the phototests led to the diagnosis of benign light
      eruption despite the unusual localization. DISCUSSION: The diagnosis of benign
      light eruption is generally clinical. Phototests are unnecessary in most cases.
      Benign light eruption can be triggered by high-dose iterative UVA exposure of the
      susceptible area or whole body phototests (UVA-UVB). These specific phototests
      are indicated in atypical forms or localizations in order to determine the course
      of benign light eruption and to uncover simulations.

PMID- 9636773
TI  - [Type B Haemophilus influenzae cellulitis in an immunocompetent adult].
AB  - INTRODUCTION: Only a few cases of Haemophilus influenzae type B cellulitis have
      been reported in adult patients. They generally involve immunocompromised
      patients, and are located in the cervico-facial areas. CASE-REPORT: We report a
      43 year-old immunocompetent patient who presented a cellulitis of the leg. No
      cutaneous or upper respiratory pathways entry portal was found. Abcedation of
      cutaneous lesions allowed the isolation of numerous colonies of Haemophilus
      influenzae type B from a subcutaneous fluid aspirate. COMMENTS: The unusual site
      of the infection, the age and the immunocompetent status of the patient, the lack
      of initial infectious localisation and the slow healing of lesions despite
      appropriated antibiotic therapy, are of particular interest.

PMID- 9636774
TI  - [Osteomalacia cured by resection of cutaneous neurinoma].
AB  - INTRODUCTION: Regression of osteomalacia after exeresis of a skin tumor is
      unusual. CASE REPORT: A 62-year-old man had suffered from bone and joint symptoms
      for several years due to osteomalacia which was confirmed both biologically and
      histologically. The patient also had a plantar neurinoma. After exeresis of the
      tumor the biological results returned to normal levels within one week followed
      by regression of the clinical signs of osteomalacia. DISCUSSION: The neurinoma in
      this patient was apparently the cause of osteomalacia, since signs of the disease
      disappeared after exeresis. To date, three cases of neurinoma associated with
      osteomalacia have been published, including a single case with skin localization.
      The tumor would secrete a substance which inhibits the synthesis of vitamin D and
      enhances phosphorus excretion.

PMID- 9636775
TI  - [Skin burns, necrosis and ulcers caused by wet cement, ready-mixed concrete and
      lime. 8 cases].
AB  - INTRODUCTION: Skin burns and caustic ulcers caused by wet cement, due to calcium
      hydroxyde, are rarely reported in the literature. They occur mostly among amateur
      cement users. OBSERVATIONS: We report seven cases of skin burns, necrosis and
      ulcerations after use of wet cement and ready-mixed concrete, and one case of
      caustic ulcers induced by wet lime. CONCLUSION: Even short skin contacts to wet
      cement or concrete may induce extensive lesions in some cases. However, we were
      not able to incriminate with certainty any special concrete additives which could
      increase skin penetration of calcium hydroxyde. Warning notices about the danger
      of skin contact should be prominent on sacked cement. When ready-mixed concrete
      is delivered, the purchaser should be handed a note explaining the risk of
      kneeling in wet concrete and the importance of protective measures. This may
      probably contribute to reduce the frequency of those accidents.

PMID- 9636776
TI  - [Shulman syndrome and anti-neutrophil cytoplasmic antibodies].

PMID- 9636777
TI  - [Systemic treatment of psoriasis by fumaric acid derivatives].

PMID- 9636778
TI  - [A case for diagnosis: follicular mucinosis].

PMID- 9636779
TI  - [A case for diagnosis: multiple digital herpes].

PMID- 9636780
TI  - [Cutaneous tumors and osteomalacia].

PMID- 9636781
TI  - [Idiopathic CD4 lymphocytopenia].

PMID- 9636782
TI  - [Diagnostic phototesting with UVA-UVB phototherapy unit: technical procedures,
      liability].

PMID- 9636783
TI  - [Question of the month. Is there any risk of prescribing methotrexate in
      psoriasis, the use of which is not legally allowed in France?].

PMID- 9636784
TI  - [Question of the month. What should be done with sexual partners?].

PMID- 9636785
TI  - [Charles Rouet (1923-1996)].

PMID- 9636786
TI  - [Erythropoietin in anesthesia and intensive care].

PMID- 9636787
TI  - [Evaluation of cognitive functions after anesthesia with propofol].
AB  - OBJECTIVES: To assess the disturbances and delay of recovery of cognitive
      functions following propofol anaesthesia, and to evaluate a series of simple
      cognitive recovery tests. STUDY DESIGN: Prospective comparative non randomized
      clinical study. PATIENTS: Two groups of non premedicated patients, of ASA
      physical class 1 and 2 were studied. The control group (n = 11) included patients
      undergoing gastric fibroscopy under local anaesthesia. The propofol group (n =
      22) consisted of patients scheduled for coloscopy under propofol anaesthesia.
      METHODS: The gastric fibroscopy was performed under local anaesthesia with
      lidocaine and the coloscopy under general anaesthesia with propofol as the sole
      anaesthetic. Five cognitive tests, designed to assess short-term memory, delayed
      memory, the ability to plan complex tasks, attention, and language comprehension
      were conducted the day before, and 1 hour, 3 hours and 6 hours after the
      endoscopy. RESULTS: The cognitive functions remained significantly depressed for
      at least 3 hours after anaesthesia, and recovered fully about 6 hours after the
      cessation of propofol administration. The capacity for planning was the most
      heavily affected. CONCLUSIONS: Complete recovery can be evaluated by simple
      cognitive tests, which showed that cognitive functions are impaired over a longer
      period than psychomotor functions. Oral instructions may therefore not be fully
      understood by the patient within 3 hours after anaesthesia, emphasizing the
      importance of written instructions and the essential role played by a well
      informed accompanying person.

PMID- 9636788
TI  - [Evaluation of the blood quality collected by cell-saver during cesarean
      section].
AB  - OBJECTIVE: To determine the quality of blood salvaged and processed during
      Caesarean section with a cell-saver. STUDY DESIGN: Laboratory study. PATIENTS:
      The study included 20 patients of ASA physical class 1 or 2 undergoing a
      scheduled Caesarean section. METHODS: A separate suction device was used from the
      beginning surgery until the delivery of the fetus, to remove most of the amniotic
      fluid coming from the surgical field. Thereafter using an Haemolite 2Plus
      (Haemonetics), the blood was separated and washed with 2 L of normal saline
      solution. Blood quality was assessed through detection of fetal cells and
      measuring out of alpha-fetal-protein, tissue factor. A Kleihauer test was also
      performed. RESULTS: Cell-saver processing removed most of alpha-fetal-protein and
      tissue factor while fetal cells were rarely seen. The Kleihauer test could not be
      performed because of haemolized blood samples. However, the results were very
      heterogeneous and after washing some salvaged units contained very high
      concentrations of alpha-fetal-protein or tissue factor. CONCLUSIONS: These
      preliminary results show that intra-operative autologous transfusion is not fully
      safe during Caesarean sections. In addition, there is an immunological risk if a
      significant part of fetal red blood cells are reinfused into maternal
      circulation. Therefore, additional studies are needed to better assess this risk.

PMID- 9636789
TI  - [Influence of arteriovenous hemofiltration on teicoplanin pharmacokinetics].
AB  - OBJECTIVE: To assess the pharmacokinetics of a single dose of teicoplanin in
      critically ill patients treated with continuous arteriovenous haemofiltration
      (CAVH). STUDY DESIGN: Prospective open clinical study. PATIENTS: Eleven patients
      with acute renal insufficiency and suspected of a Gram negative infection.
      METHOD: After injection of teicoplanin, 6 mg.kg-1 over 30 minutes the plasma and
      haemofiltrate concentrations were measured over 24 hours with high power liquid
      chromatography (HPLC). RESULTS: In plasma, the mean half-life of the first phase
      was 0.6 +/- 0.2 hour and terminal half-life was 16.4 +/- 5 8 hours, total
      clearance 30.4 +/- 7.1 mL.h-1.kg-1, volume of distribution was 0.7 +/- 0.3 L.kg-1
      and the mean resident time 19.2 +/- 7.4 hours. In the haemofiltrate, the amount
      of teicoplanin eliminated after 24 hours was less than 1% in seven patients,
      between 1.8 and 3.7% in three and reached 7% in one patient. CONCLUSION: During
      CAVH, the elimination of a single dose of teicoplanin in the haemofiltrate is
      low.

PMID- 9636790
TI  - [Hemodynamic changes induced by apnea test in patients with brain death].
AB  - OBJECTIVE: In France, an apnoea test is compulsory to confirm brain death. This
      test results in a major hypercarbia and respiratory acidosis. This study aimed to
      assess haemodynamic changes elicited by the apnoea test. STUDY DESIGN:
      Prospective clinical study. PATIENTS: Fifteen patients with brain death METHODS:
      Before the apnoea test, the lungs were ventilated with pure oxygen for 20
      minutes. Thereafter, the test was conducted with continuous oxygen flow through
      the endotracheal tube, and SpO2 monitoring. Blood gases and haemodynamic
      parameters, including systemic arterial pressure, pulmonary artery pressure,
      pulmonary artery occlusion pressure, cardiac index and right ventricular function
      parameters were assessed before, during and 20 minutes after the apnoea test.
      Mean values at the various times were compared. RESULTS: Hypercarbia and acidosis
      induced a major pulmonary hypertension and an increase in cardiac output,
      associated with a decrease in systemic vascular resistances. Despite pulmonary
      hypertension and acidosis, right ventricular function was maintained. All
      haemodynamic modifications were reversed by reventilation. CONCLUSION: Apnoea
      test induces a reversible pulmonary hypertension that is seemingly not
      deleterious for right ventricular function. Apnoea test probably does not alter
      viability of the donor's organs.

PMID- 9636791
TI  - [Diagnostic characteristics of acquired pneumonia in patients under mechanical
      respiration].
AB  - Ventilator-associated pneumonias (VAP) are the most frequent nosocomial lung
      infections. Histological diagnosis is the standard for reference. A diagnosis of
      VAP can be considered in presence of fever or hypothermia, hyperleucocytosis or
      leucopenia, worsening of blood gases, and new radiological infiltrate. Their
      diagnostical value is dependent on the number of included manifestations. A
      clinical pulmonary infection score (CPIS) has been produced and compared with
      histological data. Bacteriological data are essential for an adapted
      antibiotherapy. The blind non-protected specimen brush is inexpensive and
      reliable at levels of 10(4) and 10(6) CFU.mL-1, the sensitivity and specificity
      reach 60%. The double-protected catheter is a sensitive and specific test at the
      level of 10(3) CFU.mL-1. At present its accuracy has only been compared with
      bronchial brushing. The culture of a 20 mL mini-broncho-alveolar lavage (same
      material) is specific (50%) but not sensitive enough (< 70%) at the level of
      10(3) CFU.mL-1. The culture of the protected telescopic brush is the most
      expensive test. It does not carry a risk of contamination, but does not detect a
      significant amount of VAP even at a level below 10(3) CFU.mL-1. Due to its high
      specificity it is used as the reference test in numerous studies. The endoscopic
      broncho-alveolar lavage provides a rapid diagnosis. Although not protected, it
      carries a low risk of false positives. It also allows the diagnosis of non
      bacterial or atypical bacterial lung infections. The diagnosis can also be
      obtained with lung biopsy which however carries a risk in case of mechanical
      ventilation, whatever the technique. Except for the protected double catheter, a
      direct examination has been advocated, for the differentiation between infection
      and colonization and the improvement of the performances of the simple culture of
      the broncho-alveolar lavage (search for intra-cellular bacteria).

PMID- 9636792
TI  - [Localized rhabdomyolysis after anaphylactic shock caused by suxamethonium].
AB  - A young woman without remarkable medical history, experienced a life threatening
      anaphylactoid reaction after induction of general anaesthesia for an emergency
      curettage. Hypersensitivity reaction involving IgE antibodies against
      suxamethonium was proven by positive skin test and detection of specific IgE by
      radio-immuno assay. After intensive therapy for 2 to 3 hours, the patient
      exhibited rhabdomyolysis localized on both calves. This complication, which
      required fasciotomies, did not result in renal failure. Local and general outcome
      was good. Rhabdomyolysis was due to compartmental ischaemia following shock and
      local external compression in the lithotomy position.

PMID- 9636793
TI  - [Does flumazenil correct disorders of intracardiac conduction induced by
      accidental intravenous injection of bupivacaine?].
AB  - The authors report the case of a patient who experienced intracardiac conduction
      disturbances from accidental intravenous injection of bupivacaine, which were
      reversed by an intravenous injection of flumazenil. Flumazenil could act either
      in displacing bupivacaine from its binding site, or by an interaction involving
      the GABAergic system, unless a specific interaction between flumazenil and
      bupivacaine does exist. In case of experimental confirmation of this feature,
      flumazenil could be proposed as a new therapeutic tool for bupivacaine-induced
      cardiotoxicity.

PMID- 9636794
TI  - [Treatment of post-traumatic acute anemia by recombinant human erythropoietin in
      Jehovah's Witnesses].
AB  - A 20-year-old Jehovah's witness patient experienced a femur fracture, with a
      section of the femoral artery and vein. On admission, haemoglobin concentration
      was 5.6 g.dL-1 and haematocrit 17%. Because of aponevrotomy, blood losses
      persisted. As the patient refused blood transfusion, recombinant human
      erythropoietin and parenteral iron were administered, associated with mild
      hypothermia, sedation and mechanical ventilation. After 21 days, the haemoglobin
      concentration increased to 10.9 g.dL-1 and haematocrit to 33% Recombinant human
      erythropoietin and parenteral iron may provide an alternative safe and effective
      therapy in life-threatening anaemia when blood transfusions are not accepted by
      the patient.

PMID- 9636795
TI  - [Acute respiratory distress syndrome and pancytopenia during miliary tuberculosis
      in a HIV positive patient].
AB  - Acute respiratory distress syndrome (ARDS) is a rare but severe complication of
      miliary tuberculosis, which may occur even under antituberculous therapy. Even
      with adequate treatment, its mortality is close to 70%, and if associated with
      pancytopenia, it may reach 100%. Underlying diseases, delayed diagnosis and
      additional complications are factors of poor prognosis. We report a case of a
      patient infected with the human immunodeficiency virus who experienced
      pancytopenia and ARDS associated with miliary tuberculosis. The patient recovered
      under antituberculous chemotherapy.

PMID- 9636796
TI  - [Factor XI deficiency, a new way of substitution: human purified concentrates].
AB  - Case report of a 26-year-old patient, admitted for severe craniofacial trauma,
      with facial injuries and intracranial haemorrhage. Preoperative tests showed an
      aPTT = 64 s (control = 29 s), rapidly recognized as being caused by a major
      constitutional factor XI deficiency (0.06 Ul.mL-1). Considering the neurological
      risk and the indication for surgery, concentrates of factor XI were administered
      at a dosage of 25 Ul.kg-1. This treatment was associated with a biological
      normalization and uneventful surgery. In patients experiencing a factor XI
      deficiency, the use of fresh frozen plasma will probably decrease and only
      administered in emergency cases when factor XI concentrates are not available.

PMID- 9636797
TI  - [Substances responsible for peranesthetic anaphylactic shock. A third French
      multicenter study (1992-94)].
AB  - Since 1989, the epidemiological survey of anaphylactoid reactions occurring
      during anaesthesia is obtained in France with repeated inquiries by the
      Perioperative Anaphylactic Reactions Study Group. The members of this group
      collect during the study period the cases of patients having suffered from an
      anaphylactoid reaction and tested in their allergo-anaesthetic outpatient clinic,
      their characteristics (age, gender), the results of the allergological tests
      (mechanism, agents responsible for the reactions). The two previous surveys
      published in the Annales francaises d'anesthesie et de reanimation in 1990 and
      1993 included 1,240 and 1,585 patients respectively. The current survey concerned
      1,750 patients tested in 27 diagnostic centres, from January 1992 to June 1994.
      The reactions occurred at all ages, predominantly between 10 and 50 years, the
      sex-ratio (F/M) was 2.4. Allergological tests carried out to diagnose an immune
      mechanism for the shock were cutaneous tests in all centres (prick-tests in 21
      centres, intradermal tests in 27 centres) using the same dilutions for the tested
      agents and the same threshold for positivity. Specific IgE antibodies against
      muscle relaxants, thiopentone and propofol, were measured by radio immunoassays
      in 20 centres. The leucocyte histamine release test was used in 10 centres. The
      immune origin of the shock--IgE dependent anaphylaxis--was diagnosed in 1,000
      patients (57.8%) and due to 1,030 agents muscle relaxants (59.2%), latex (19%),
      hypnotics (5.9%), benzodiazepines (2.1%), opioids (3.5%), plasma substitutes
      (5%), antibiotics (3.1%) and other drugs given during anaesthesia such as
      aprotinine and protamine (2.2%). Suxamethonium was responsible for 39.3% of
      muscle relaxant anaphylaxis, vecuronium for 36%, atracurium for 14.5%,
      pancuronium for 4.8%, gallamine for 3.1% and alcuronium for 2.3%. The latter has
      been withdrawn from the French market in 1993. These differences in the incidence
      of reactions are correlated with the clinical use of muscle relaxants in France
      for vecuronium and atracurium, however not for suxamethonium, responsible for 39%
      of the reactions but representing only 5% of the muscle relaxants sold in France.
      The comparison with the two previous surveys confirms that the mechanism of more
      than half of the anaphylactoid reactions occurring during anaesthesia is of
      immune origin, due to specific IgE antibodies. It is therefore essential to
      systematically carry out an allergologic assessment several weeks after the
      reaction, in order to discard for the subsequent anaesthetics the agent(s)
      responsible for anaphylaxis. If the muscle relaxants remain the first drugs
      involved in shock occurring at induction, there is a significant increase in
      latex shock, as demonstrated by the three epidemiological surveys (0.5%, 12.5%
      and now 19%). The incidence of other anaesthetic agents, antibiotics and plasma
      substitutes remains unchanged.

PMID- 9636798
TI  - [Blood transfusion in surgery: can it still be reduced by human recombinant
      erythropoietin?].
AB  - New agents such as recombinant human erythropoietin (rHu EPO) modify conventional
      transfusionnal strategies. For accurate indications, such as, anaemia associated
      with chronic renal failure, cancer or cardiac disease, the preoperative
      prescription of rHu EPO may reduce transfusion requirements. rHu EPO may also be
      associated with pre-deposit transfusion in patients with anaemia before blood
      donation, when the transfusion needs are high, or the period for blood pre
      deposit donation shortened. Postoperatively rHu EPO is only efficient if it is
      administered for a prolonged period; this condition limits its indications and
      value because of its high cost.

PMID- 9636799
TI  - [A new device for free airway maintenance during anesthesia: cuffed oropharyngeal
      airway].

PMID- 9636800
TI  - [Ketoacidotic coma, a way to discover severe acute pancreatitis in a non-diabetic
      patient treated with acitretin].

PMID- 9636801
TI  - [Anesthetic drugs available for mobile health unit physicians in France].

PMID- 9636802
TI  - [Foreign body in the pharynx during intubation].

PMID- 9636803
TI  - [Legionellosis and enteritis].

PMID- 9636804
TI  - Immunotherapy as an effective tool in allergy treatment.

PMID- 9636805
TI  - Risk and safety of immunotherapy.
AB  - The risk and safety of specific immunotherapy (SIT) has been the subject of many
      well-designed studies since it was introduced. Most authors consider SIT an
      efficient and safe mode of treatment despite the occurrence of life-threatening
      anaphylactic reactions. They emphasize the importance of a proper selection of
      patients as well as the requirement for highly qualified physicians to provide
      the treatment. Another problem associated with the safety of SIT is the potential
      enhancement of the synthesis of immune complexes after the treatment. SIT causes
      a decrease in allergen-specific IgE which is slower in circulating immune
      complexes than in the serum. No data are available to show that SIT induces
      immune-complex diseases, in either the immunologic or the clinical sense. As far
      as anaphylactic reactions are concerned, new alternative methods different from
      the conventional parenteral mode of delivery seem to be safe. Our increased
      understanding of the altered functions of the immune system justifies the
      assumption that the more specific the method of SIT administration, the more
      effective and safe it is.

PMID- 9636806
TI  - Local immunotherapy: pharmacokinetics and efficacy.

PMID- 9636807
TI  - Mechanisms of specific immunotherapy of allergic diseases.

PMID- 9636808
TI  - Clinical efficacy of sublingual-swallow immunotherapy: a double-blind, placebo
      controlled trial of a standardized five-grass-pollen extract in rhinitis.
AB  - Sublingual-swallow immunotherapy (SLIT) using high doses of standardized allergen
      extracts has been found to be effective in reducing allergic symptoms and
      medication needs. A double-blind, placebo-controlled study was carried out in a
      large number of patients to determine whether medication needs can be reduced by
      SLIT. Some 136 patients with grass-pollen rhinitis with or without mild asthma
      were studied. Patients received either placebo or SLIT with a standardized grass
      pollen extract administered daily with increasing doses up to 300 IR (index of
      reactivity) from January to the end of July 1994. During the grass-pollen season,
      patients were instructed to use medications as required and to visit their
      doctors in case of asthma. Symptom-medications scores were assessed during the
      pollen season, and serum-specific IgG4 was measured before and at the end of
      SLIT. In the SLIT group, drug consumption dropped significantly throughout the
      pollen season (P < 0.02). Moreover, at the peak of the pollen season,
      betamethasone consumption was significantly reduced in the SLIT group (P < 0.02).
      Only one patient in the SLIT group had an asthma attack compared to eight
      patients in the placebo group (P < 0.02). IgG4 levels increased significantly in
      the SLIT group (P < 0.001) but without correlation with symptoms. Side-effects
      were comparable in both groups. This study indicates that SLIT in grass-pollen
      rhinitis is well tolerated, improves overall clinical symptoms, and reduces drug
      consumption and the need for oral corticosteroids.

PMID- 9636809
TI  - Guanine, mite, and cockroach allergens in Costa Rican homes.
AB  - Previous studies of schoolchildren in Costa Rica have shown an asthma prevalence
      of 23% and a high level of sensitization, particularly to mite allergens. As a
      continuation of these studies, some 400 dust samples were collected from various
      places in Costa Rica, and parts of these were analyzed for specific mite and
      cockroach allergens, as well as for the number of mites and amount of guanine.
      Guanine was quantified by a diazo, as well as an HPLC method, which were found to
      be highly correlated. The concentrations of guanine by the diazo method, Der p 1,
      Der f 1, and the number of mites were higher in bed dust than in bedroom floor
      dust, and it was possible to quantify mite allergens and guanine in almost all
      bed-dust samples. The mean levels were 2-3 times higher than the proposed risk
      level for elicitation of symptoms in mite-sensitive asthmatics. Bed and bedroom
      floor dust contained more guanine and mite allergen in humid (> 2000 mm rain)
      than in drier places (P < 0.05), but the number of mites in bed and bedroom floor
      dust was higher in less humid places (P = 0.01). The guanine content in bedroom
      floor dust was higher in areas with a temperate climate than in areas with a
      warmer climate (P < 0.001, Bartlett's chi square [BCS]), as was the number of
      mites (P < 0.01, Kruskal-Wallis [KW], 0.04, BCS) and the Der p 1 concentration (P
      = 0.01, BCS; P = 0.02, KW). The Der f 1 concentration in bedroom floor dust was
      higher in a warmer than in a temperate climate (P < 0.001, BCS). More guanine and
      mites were found in urban than in rural bed dust (P = 0.03, KW). Dust samples
      from the metropolitan area (temperate climate) of Costa Rica contained higher
      levels of guanine (P < 0.01) and Der p 1 (P = 0.07) than the coastal areas, but
      very little Der f 1. In these samples, guanine and Der p 1 allergen were closely
      related, and 2 micrograms of the allergen was equivalent to 0.49 mg of guanine.
      Two-thirds of bed and floor samples collected on cotton filters contained Bla g 2
      allergen at mean levels of 1.6 and 2.1 units/g dust, respectively. Cockroach
      allergen was, however, absent in all bed samples from the metropolitan area, but
      did occur in very high concentrations in the coastal bed dust samples collected
      with tighter polyester filters. In conclusion, the concentration of guanine and
      Der p 1 was very high in the bed dust of Costa Rican homes. Some factors, such as
      humidity, small houses for large families, and type of bedding, probably favored
      the heavy mite infestation, which is probably related to the widespread
      occurrence of bronchial asthma in this country.

PMID- 9636810
TI  - IgE, IgA, and IgG responses to common yeasts in atopic patients.
AB  - This study was undertaken to analyze the differences in exposure and
      sensitization to five common environmental yeasts. The responses of IgG, IgA, and
      IgE to Candida albicans, C. utilis, Cryptococcus albidus, Rhodotorula rubra, and
      Saccharomyces cerevisiae and purified S. cerevisiae enolase were analyzed by
      immunoblotting (IgE-IB), and the cross-reactivity of their IgE-binding components
      by IgE-IB inhibition. Twenty atopic subjects, with asthma, allergic rhinitis, or
      atopic dermatitis were included. In skin prick tests (SPT), 12 of the patients
      showed simultaneous reactivity to at least two of the five yeasts, four reacted
      to one of the yeasts, and four had no responses. Antigens run in SDS-PAGE and
      transferred to nitrocellulose were probed with enzyme-labeled IgA-, IgG-, and IgE
      specific antibodies. The IgE immunoblotting revealed most IgE-binding bands in C.
      albicans (11 bands) followed by C. utilis (eight bands), S. cerevisiae (five
      bands), R. rubra (five bands), and Cr. albidus (four bands). Six of the IgE
      binding bands of C. albicans and C. utilis shared molecular weight, and only two
      bands shared molecular weight with other yeasts. These were the 46-kDa band,
      shared by all five yeasts, and a 13-kDa band shared by four yeasts. Prominent IgE
      binding was seen to a 46-kDa band of C. albicans (seven patients), C. utilis
      (five patients), and S. cerevisiae (one patient) and to corresponding weak bands
      of Cr. albidus and R. rubra (one patient). The possible cross-reactivity of the
      46-kDa band was analyzed by IgE-IB inhibition and densitometry, revealing clear
      C. albicans inhibition of C. utilis (80%) and enolase (98%) (autoinhibition
      100%). The strongest IgG responses were seen against S. cerevisiae and C.
      albicans. The responses were mainly against mannans of C. albicans and S.
      cerevisiae, suggesting that most of the exposure is to these yeasts. Yeasts with
      different types of exposure, from saprophytic growth on human mucous membranes to
      exposure by air and food, were shown to cross-react at the allergenic level.
      Atopic patients primarily sensitized by C. albicans and S. cerevisiae may develop
      allergic symptoms by exposure to other environmental yeasts due to cross-reacting
      IgE antibodies.

PMID- 9636811
TI  - Amino acid sequence similarity of Hev b 3 to two previously reported 27- and 23
      kDa latex proteins allergenic to spina bifida patients.
AB  - Separate studies have reported spina bifida patients to be especially allergic to
      proteins of 27 and 23 kDa found in the serum of centrifuged natural rubber latex.
      An insoluble latex protein located on the surface of small rubber particles, Hev
      b 3, has similarly been found to be allergenic to spina bifida patients. In this
      study, internal amino acid sequences of Hev b 3 showed similarity to the
      published sequences for the 27- and 23-kDa latex proteins. The latter allergens
      are hence identified as Hev b 3. Determination of the molecular weight of Hev b 3
      revealed various species of 22-23 kDa. The consistent gaps of about 266 Da
      observed between various forms of the intact protein suggest that the protein
      undergoes post-translational modification. To determine whether Hev b 3 also
      occurs in a soluble form in the latex serum, its presence in molecular-filtered
      serum was checked by ELISA and Western blot. The results showed Hev b 3 to be
      largely absent in the C-serum from fresh latex. The protein is therefore
      insoluble in its native state. However, a small amount of the solubilized protein
      was detected in ammonia-stabilized latex (commonly used in the manufacture of
      latex products).

PMID- 9636812
TI  - Olive-pollen profilin. Molecular and immunologic properties.
AB  - Olive-pollen profilin has been isolated and characterized as a significant
      allergen. Its molecular properties, such as a molecular mass of 15 kDa; amino
      acid composition; and secondary repetitive structure percentages of 15% alpha
      helix, 33% beta-strand, 20% beta-turn, and 32% random coil, have been determined.
      Its allergenic capability, a recognition frequency estimated at 24% of olive
      hypersensitive patients, and high cross-reactivity with all the pollen used have
      been found. The presence of conformation epitopes in the olive profilin, as well
      as a high structural and immunologic similarity to other pollen sources such as
      birch and ash, can be established from these studies.

PMID- 9636813
TI  - CD86 (B7-2) antigen on B cells from atopic patients shows selective, antigen
      specific upregulation.
AB  - To determine whether B7 signals are associated with atopic responses in man, we
      assayed CD80 and CD86 expression on B cells and monocytes from atopic patients
      and controls. Peripheral blood mononuclear cells from 10 patients with perennial
      allergic rhinitis and from 10 normal subjects were cultured in the presence or
      absence of house-dust-mite antigen, and B cells and monocytes were assayed for
      expression of CD80 and CD86 by flow cytometry. CD86 on B cells was significantly
      and selectively upregulated in all atopic subjects, but not in normal subjects,
      whereas CD80 expression was not altered in B cells from the atopic subjects or
      controls. In contrast, both CD80 and CD86 were upregulated in monocytes from the
      atopic subjects as well as the controls. However, CD86 upregulation was
      significantly higher in the atopic subjects than in controls. Our results seem to
      suggest that selective upregulation of CD86 on B cells by a challenging antigen
      may play a critical role in the development of Th2 cells in patients with atopic
      disease.

PMID- 9636814
TI  - Latex allergy in fruit-allergic patients.
AB  - The purpose of this study was to investigate the prevalence of latex allergy in
      fruit-allergic patients, and to assess its clinical significance. Fifty-seven
      fruit-allergic patients and 50 non-fruit-allergic atopic patient controls were
      studied. All patients were questioned about conventional immediate symptoms after
      contact with latex products. Patients also underwent skin prick testing and
      determination of specific serum IgE to latex, as well as a screening test for
      environmental allergens. Immunologic latex sensitization occurred in 49/57
      (85.9%) fruit-allergic patients, who showed a positive STP and/or CAP to latex,
      but in only two controls (P < 0.001). Six out of 57 (10.5%) fruit-allergic
      patients suffered from clinically relevant latex allergy. Symptoms included
      contact urticaria, angioedema, conjunctivitis, generalized urticaria, and
      moderate anaphylactic reactions. No control reported symptoms with latex products
      (P = 0.052). In all patients, clinical symptoms to fruits preceded a history of
      latex allergy. The fruits most associated were melon, peach, and banana. From our
      data, we conclude that there is a potential for allergic reactions to latex in
      patients with allergy to fruit. All patients with fruit allergy should be
      screened for individual risk of latex allergy.

PMID- 9636815
TI  - BCG vaccination does not seem to prevent atopy in children with atopic heredity.

PMID- 9636816
TI  - Cross-reactivity between buckwheat and latex.

PMID- 9636817
TI  - Allergy to mare's milk.

PMID- 9636818
TI  - Occurrence of allergens in hospital premises.

PMID- 9636819
TI  - Preoperative screening for general anesthesia.

PMID- 9636820
TI  - Ascites in hereditary angioedema.

PMID- 9636822
TI  - Your metered-dose inhaler will be changing.

PMID- 9636821
TI  - Loratadine reduces the expression of ICAM-1.

PMID- 9636823
TI  - Cost-effectiveness of interferon-alpha for chronic myeloid leukemia.

PMID- 9636824
TI  - PET scanning in clinical oncology.

PMID- 9636825
TI  - Predicting hematological toxicity (myelosuppression) of cytotoxic drug therapy
      from in vitro tests.
AB  - Several clinical oncology units are studying the roles of in vitro
      hematotoxicology in phase I evaluations. At the same time, the European Center
      for the Validation of Alternative Methods (ECVAM) is supporting a validation
      study of the CFU-GM assay. It is important that these activities be coordinated
      so that high performance, optimized technical protocols are used for prospective
      and retrospective clinical evaluations. The EROTC, the NCI and ECVAM could
      provide support for these coordinated efforts. There is an opportunity for
      medical oncologists involved in early clinical trials to participate in the
      evaluation of in vitro tests and their clinical application . Fundamental to
      acceptance of these assays by oncologists and regulatory scientists, they must
      predict clinical outcome for myelosuppressive agents and then improve phase I
      design and performance. These achievements would justify more aggressive dose
      escalation schemes using guidance from in vitro studies without compromising
      patient safety. Success in predicting neutropenia might also stimulate the
      research required to understand how to predict other hematologic toxicities, such
      as a thrombocytopenia. The complexity of a validation study in hematotoxicology
      is that it seeks to predict the level of exposure that causes neutropenia, in
      contrast to other validation studies that have sought to classify a xenobiotic as
      toxic or not. It may be that the clinical relevance of a new assay is not just a
      yes-no answer. This important distinction came from the realization that the
      xenobiotic tolerance in other organ systems of the body must be the same or
      greater than marrow in order for myelosuppression to be a clinical consequence of
      exposure. Pharmacological principles of system exposure and toxicity that are
      integrated into the prediction model provide the links to clinical oncology. It
      is also important to anticipate future applications of in vitro hematotoxicology.
      If the maximum tolerated level of drug exposure for human hematopoietic cells can
      be predicted, then in vitro hematotoxicology could play an important role in new
      drug discovery. One concept involves screening for compounds that show efficacy
      at the IC level that predicts maximum tolerated exposure levels in the human.
      'Therapeutic index based' drug discovery has been applied to the tallimustine
      family with some success.

PMID- 9636826
TI  - Do specialists do it better? The impact of specialization on the processes and
      outcomes of care for cancer patients.
AB  - OBJECTIVE: To assess the impact of specialization on processes and outcomes of
      care for cancer patients. DATA SOURCE: Papers published in English between 1980
      and 1995 and identified through MEDLINE and Embase (MeSH terms: NEOPLASM
      (exploded), and PHYSICIAN PRACTICE PATTERNS (or DECISION MAKING, ATTITUDE OF
      HEALTH PERSONNEL, QUALITY OF HEALTH CARE, DELIVERY OF HEALTH CARE, HEALTH
      EDUCATION or OUTCOME ASSESSMENT HEALTH CARE), or through the reference lists of
      review articles. STUDY SELECTION: Studies providing information on the
      association between quality of care indicators for cancer patients and
      clinician/centre degree of specialization. A total of 47 papers concerning 46
      empirical studies were considered. DATA EXTRACTION: For studies using process of
      care indicators, the proportion of specific procedures performed by specialists
      and non-specialists was abstracted. For studies using outcome indicators (e.g.,
      mortality), the effect of specialization was quantified in terms of odds ratio
      (OR) expressing relative reduction in risk of death. The quality of individual
      studies using process or outcome indicators was assessed according to study
      design, avoidance of selection bias in patient identification and data analysis,
      degree of adjustment of the comparison between clinicians/centres with different
      levels of specialization. DATA SYNTHESIS: Specialized centres/clinicians fared
      better both when process and outcome indicators were used. While the former
      varied widely in different studies and their clinical relevance was often
      questionable, mortality was consistently lower when care was provided by
      specialized centres/clinicians, with the effect size being greater in smaller
      studies. For breast cancer, where all the studies were of sufficiently good
      quality, a pooled estimate of the effect of specialization was performed which
      showed that specialized cancer care was associated with an 18% (95% CI: 12%-23%)
      reduction in mortality. CONCLUSIONS: Despite the fact that care provided by
      specialized centres/clinicians appeared to be better both when assessed in
      relation to process indicators and to mortality, this evidence should be
      considered far from conclusive because of major methodological flaws in these
      studies. Relative to current efforts to promote evidence-based policy-making,
      this review underscores the limited capability of scientific information to
      provide reliable guidelines for structuring better health care systems.

PMID- 9636827
TI  - Searching the medical literature for the best evidence to solve clinical
      questions.

PMID- 9636828
TI  - Successful treatment with lamivudine for fulminant reactivated hepatitis B
      infection following intensive therapy for high-grade non-Hodgkin's lymphoma.
AB  - Chronic carriers of Hepatitis B virus (HBV) infection, who are treated for
      malignant lymphoma, are at high risk of mortality from reactivated HBV infection.
      We report a case of a 29-year-old male chronic HBV carrier who developed
      fulminant reactivated HBV infection following intensive chemotherapy for stage
      IVB large cell B-cell non-Hodgkin's lymphoma associated with extensive central
      nervous system and bone marrow involvement. Prior to chemotherapy the patient had
      normal liver function tests and was negative for HBV DNA by semiquantitative PCR
      assay. Fulminant HBV reactivation was confirmed following clinical deterioration,
      massive rises in hepatic transaminases (peak alanine aminotransferase = 2,850
      U/l), liver biopsy and rising levels of serum HBV DNA. Following treatment with
      lamivudine 150 mg bd for 18 weeks dramatic and sustained recovery ensued.
      Symptoms and liver function tests improved within days and HBV DNA became
      negative within 12 weeks. Our patient later died from relapsed lymphoma but
      without evidence of reactivated HBV infection. We advise that lamivudine should
      be considered during intensive chemotherapy treatment of chronic carriers of HBV.

PMID- 9636829
TI  - Cost-effectiveness of interferon in chronic myeloid leukaemia: analysis of four
      clinical studies.
AB  - BACKGROUND: Analysis of published survival curves can be used as the basis for
      incremental cost-effectiveness analyses in which two treatments are compared with
      one another in terms of cost per life-year saved. In patients with chronic
      myeloid leukaemia in chronic phase, long-term treatment with alpha-interferon has
      been reported to improve survival in comparison with standard treatments with
      cytotoxic drugs. To assess the pharmacoeconomic profile of interferon treatment
      in terms of cost per life-year gained, we conducted an incremental cost
      effectiveness analysis. PATIENTS AND METHODS: The clinical material utilised in
      our analysis derived from four published randomised trials comparing interferon
      vs. busulphan or hydroxyurea. The Gompertz model was used to estimate the total
      lifetime values of patient-years of subjects receiving interferon in comparison
      with subjects given a standard cytotoxic treatment. RESULTS: Our primary analysis
      showed that maintenance treatment with interferon improved survival expectancy by
      37 to 93 discounted years for every 100 patients. The incremental cost
      effectiveness ratio of interferon vs. cytotoxic therapy ranged from $93,000 to
      $226,000 per life-year gained (discounted costs per discounted years). A
      secondary analysis showed that the dose of interferon had significant influence
      on the cost-effectiveness ratio. Because our literature search identified a fifth
      study that showed an extremely favourable outcome using interferon but that was
      not included in our primary analysis due to its design, we conducted another
      secondary analysis based on these five studies that, however, confirmed the
      results of the primary analysis. CONCLUSIONS: Our study indicates that an
      unselected long-term treatment with interferon implies an unfavourable cost
      effectiveness ranking in comparison with data of cost per life-year gained which
      had previously been obtained from other types of medical intervention.

PMID- 9636830
TI  - Clinical evaluation of whole-body 18F-fluorodeoxyglucose positron emission
      tomography in the detection of liver metastases.
AB  - BACKGROUND: Assessment of metastatic involvement of the liver remains a
      diagnostic challenge. The objective of this study was to evaluate the potential
      role of FDG PET in the detection of liver metastases. PATIENTS AND METHODS: Sixty
      four patients with malignancy and possible liver involvement were included. Liver
      metastases were present in 31 cases, demonstrated by histopathological analysis
      in 15 cases and by follow-up in 16 cases. The negative cases were confirmed by
      pathology in four cases, peroperative ultrasonography in 12 cases, and follow-up
      in 17 cases. Whole-body FDG PET was compared to CT (n = 53) and US (n = 43).
      RESULTS: PET demonstrated a 97% sensitivity, an 88% specificity and a 92%
      accuracy, compared to 93%, 75% and 85%, respectively, for CT (P = NS). Concordant
      results were obtained in 44 of 64 patients (69%: 19 TP. 25 TN). PET provided new
      and accurate information in 15 of 64 patients (23.4%). PET demonstrated liver
      metastases in 11 patients in whom conventional methods yielded negative (two
      cases) or doubtful (nine cases) results. Four patients free of liver involvement
      were correctly staged with PET, while CT/US were equivocal. PET was erroneous in
      five of 64 cases (7.8%, four FP, one FN). CONCLUSIONS: FDG PET allows an accurate
      screening of liver involvement in patients with malignancy. Combined with CT, it
      provides additional diagnostic information that could directly affect the
      management of these patients.

PMID- 9636831
TI  - Dosage of adjuvant G-CSF (filgrastim)-supported FEC polychemotherapy based on
      equivalent haematological toxicity in high-risk breast cancer patients.
      Scandinavian Breast Group, Study SBG 9401.
AB  - BACKGROUND: Conventional dosages of cytostatics in mg/m2 will cause marked
      variations in systemic exposure, resulting in over- and under-treatment, at least
      with respect to side effects. PATIENTS AND METHODS: We are conducting a
      randomized adjuvant study for breast cancer patients younger than 60 years of age
      with > or = 70% risk of recurrence within five years. The first 89 consecutive
      patients who have received nine courses q three weeks of individually dose
      escalated and G-CSF (filgrastim)-supported FEC (5-fluorouracil (5-FU),
      epirubicin, and cyclophosphamide) therapy given with ciprofloxacin prophylaxis
      were included in this analysis. Six different FEC dose levels were used for
      treatment at equivalent haematological toxicity. Dose modifications were based on
      white blood cell and platelet counts on days 8, 11/12, 15, and 22. RESULTS:
      Eighty-three of 89 patients completed all nine courses. The median epirubicin and
      cyclophosphamide doses were 782 mg/m2 (range 0-994 mg/m2) and 10.330 mg/m2 (range
      0-14.460 mg/m2), respectively. Patients treated at the two highest dose levels
      experienced NCl grade 0 or 1 toxicities in 73% to 92% of the courses. Three
      patients have developed acute myeloid leukaemia, and two of them have
      demonstrated abnormalities compatible with topoisomerase II-poison-related
      karyotypic changes. CONCLUSIONS: Tailored adjuvant G-CSF-supported FEC
      polychemotherapy will make it possible for all patients to be treated at
      equivalent levels of haematological toxicity with significantly higher doses
      without a marked increase in other organ toxicities.

PMID- 9636832
TI  - Clinical course of breast cancer patients with metastases confined to the lungs
      treated with chemotherapy. The University of Texas M.D. Anderson Cancer Center
      experience and review of the literature.
AB  - PURPOSE: To evaluate the clinical course of patients with a metastatic breast
      cancer (MBC) confined to the lungs and treated with doxorubicin/cyclophosphamide
      containing chemotherapy (DC-CT). PATIENTS AND METHODS: Between 1973 and 1985,
      1581 patients with MBC were treated with DC-CT at M.D. Anderson Cancer Center.
      Data for 88 patients (5.6%) with metastases confined to the lungs were reviewed
      to correlate various clinical characteristics with response to treatment and
      survival. RESULTS: The overall response rate was 76% with 33% achieving complete
      response (CR). The median overall survival time was 22 months (range 1-210). The
      10-year survival rate was 9%. The overall response and CR rates were higher for
      the patients with metastases confined to the lungs (76% and 33%. respectively)
      than for the remainder of MBC patients (64% and 14%; P < 0.01). The 10-year
      survival rate was also higher (9% versus 3%, P < 0.01), but there were no
      differences in median overall survival rate. CONCLUSIONS: This retrospective
      analysis demonstrated that patients with metastases confined to the lungs treated
      with DC-CT had a high objective response rate, especially high CR rates, and a
      median survival comparable to that of our entire population of MBC patients. A
      small but clinically significant percentage of patients had prolonged survival.
      Therefore, not all visceral sites are indicators of poor prognosis.

PMID- 9636833
TI  - Survival of patients with visceral metastatic melanoma from an occult primary
      lesion: a retrospective matched cohort study.
AB  - BACKGROUND: Malignant melanoma presents as metastatic disease without an apparent
      primary in about 4% of cases. These are referred to as occult primary melanoma
      (OPM). It is not known whether these represent de novo malignant transformation
      in non-cutaneous sites or the disappearance of an unrecognised primary, perhaps
      on an immunological basis. We hypothesised that OPM might have a superior
      prognosis compared to patients with similar disease extent from a known primary
      lesion (KPM). PATIENTS AND METHODS: We performed a retrospective cohort survival
      study of 146 patients with OPM and visceral metastases treated at the Sydney
      Melanoma Unit between 1983 and 1996. A control group of patients with KPM was
      matched for age, sex and site of visceral metastases. Survival was measured from
      the date of diagnosis of visceral metastases. RESULTS: Patients with OPM had a
      median survival of 233 days, significantly longer than the 176 days for those
      with KPM (P = 0.024; logrank test). Multivariate analysis allowing for
      simultaneous or prior involvement of lymph nodes, subcutaneous tissues or bone,
      and site of visceral involvement showed a significantly superior survival for OPM
      (hazard ratio (HR): 0.72; 95% confidence interval (CI): 0.55-0.93). A small part
      of the effect was explained by treatment, but models allowing for this still
      showed a significantly longer survival. CONCLUSIONS: Survival was longer in OPM
      patients. This may reflect an intrinsically superior host-tumour interaction.

PMID- 9636834
TI  - Ovarian cancer cisplatin-resistant cell lines: multiple changes including
      collateral sensitivity to Taxol.
AB  - BACKGROUND: Alteration in apoptosis pathways (in particular mutations of p53
      gene) may result in resistance of ovarian carcinoma to cisplatin. However,
      cisplatin resistance is likely to be multifactorial. An understanding of the
      molecular alterations associated with the development of resistance may be of
      considerable relevance in an attempt to optimize the therapeutic approach. STUDY
      DESIGN: Two cisplatin-resistant sublines (IGROV-1/Pt0.5 and IGROV-1/Pt1), both
      characterized by mutant p53 (Cancer Res 1996; 56: 556-62), but with different
      degree of resistance were studied in terms of pattern of cross-resistance,
      susceptibility to drug-induced apoptosis, expression of gluthathione-dependent
      system, cellular pharmacokinetics, drug-induced DNA damage. The resistance index
      (ratio between the IC50 of resistant and sensitive cells) after a 96-hour drug
      exposure was 10 for IGROV-1/Pt0.5 and 14 for IGROV-1/Pt1 cells. RESULTS:
      Resistant cells were cross-resistant to DNA-damaging agents and, interestingly,
      they had a collateral sensitivity to Taxol. The cellular response to Taxol
      paralleled the drug ability to induce apoptosis. The intracellular glutathione
      level was significantly increased in IGROV-1/Pt cells compared to the sensitive
      counterpart. In contrast, glutathione S-transferase level was consistently
      reduced in both sublines. gamma-Glutamyl transpeptidase activity, which was lower
      in resistant than in sensitive cells, was not directly correlated with
      glutathione level, thus suggesting a complex regulation of cellular glutathione
      content. In the resistant cells with the highest glutathione content, a reduced
      level of cisplatin-induced cross-link was found. Analysis of DNA platination
      revealed a slight decrease of DNA-bound platinum only in IGROV-1/Pt1 cells.
      Again, this reduction is consistent with a protective role for glutathione. The
      expression of metallothionein IIa was increased in both resistant variants.
      CONCLUSIONS: Multiple changes are involved in acquired resistance of ovarian
      carcinoma cells including reduced susceptibility to apoptosis as consequence of
      inactivation of p53 and expression of defence mechanisms. The relative
      contribution is related to the degree of drug resistance. In particular, the
      glutathione-dependent system could have a role only in the development of a high
      degree of resistance. Finally, the finding that Taxol was very effective in
      inducing apoptosis in resistant sublines with p53 mutation supports the
      expression of an intact p53-independent pathway of apoptosis and suggests the
      pharmacological interest of Taxol in the treatment of p53-mutated tumors.

PMID- 9636835
TI  - A novel cancer vaccine composed of human-recombinant epidermal growth factor
      linked to a carrier protein: report of a pilot clinical trial.
AB  - BACKGROUND: There is evidence of a relationship between epidermal growth factor
      (EGF) and tumor cell proliferation, such as the overexpression of EGF receptor
      (EGF-R) in different human tumors, which makes this system an interesting target
      for cancer treatment. Up to now, passive immunotherapy with monoclonal antibodies
      against the EGF-R has been assayed in clinics. Our approach consists of active
      immunotherapy with human EGF (hu-EGF). We conducted a pilot clinical trial to
      define the safety, toxicity and immunogenicity of vaccination with hu-EGF coupled
      to a carrier protein. PATIENTS AND METHODS: Ten patients with histologically
      proven malignant carcinomas (colon, lung, stomach and prostate) in advanced
      clinical stages were enrolled. Patients were immunized twice (on days 0 and 15)
      with hu-EGF linked to either tetanic toxoid (TT, five patients) or P64K Neisseria
      Meningitidis recombinant protein (P64k, five patients), intradermically, using
      aluminium hydroxyde as adjuvant. RESULTS: In both groups 60% of patients
      developed anti-EGF antibody titers without evidence of toxicity. Secondary
      reactions were very mild, limited to erythema and itching at the site of
      injection, which disappeared without medication. CONCLUSIONS: We conclude that
      the proposed vaccination with hu-EGF was well tolerated and that antibody titers
      against self EGF were developed. The results of this trial may be useful in the
      design of new clinical trials with higher dose immunization protocols and using
      more effective adjuvants.

PMID- 9636836
TI  - Malignant effusions contain lysophosphatidic acid (LPA)-like activity.
AB  - BACKGROUND: Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are
      bioactive phospholipids with mitogenic and growth factor-like activities that act
      via specific cell-surface receptors present in many normal and transformed cell
      types. LPA has recently been implicated as a growth factor present in ascites of
      ovarian cancer patients. The presence of LPA-like activity and the hypothesis
      that levels of this bioactivity in effusions of ovarian cancer patients are
      higher than those in effusions of other cancer patients was studied. MATERIALS
      AND METHODS: A neurite retraction bioassay in a neuroblastoma cell line
      previously developed for in vitro detection of LPA activity on cell lines was
      employed and bioactivity was expressed in virtual LPA-equivalent levels. LPA
      equivalent levels were tested in effusions of 62 patients with a range of
      malignancies, including 13 ovarian cancer patients. Biochemical and clinical
      parameters were evaluated for correlations with LPA-equivalent levels. RESULTS:
      Average LPA-equivalent levels were 50.2 microns (range 5.4-200) for all patients,
      and 94.5 microns (range 15-200) for ovarian cancer patients (P = 0.004). There
      were no additional independent significant correlations between LPA-equivalent
      levels in effusions and a range of other biochemical and clinical
      characteristics. CONCLUSION: These data suggest a role for LPA-like lipids in the
      peritoneal spread of ovarian cancer and possibly that of other predominantly
      intraperitoneal malignancies.

PMID- 9636837
TI  - Carboplatin toxic effects on the peripheral nervous system of the rat.
AB  - BACKGROUND: The most striking of carboplatin's advantages (CBDCA) over cisplatin
      (CDDP) is its markedly reduced rate of neurotoxic effects. However, the use of
      CBDCA higher-intensity schedules and the association with other neurotoxic drugs
      in polychemotherapy may cause some concern about its safety with respect to
      peripheral nervous system damage. MATERIALS AND METHODS: Two different schedules
      of CBDCA administration (10 mg/kg and 15 mg/kg i.p. twice a week for nine times)
      were evaluated in Wistar rats. Neurotoxicity was assessed for behavioral (tail
      flick test), neurophysiological (nerve conduction velocity in the tail nerve),
      morphological, morphometrical and analytical effects. RESULTS: CBDCA
      administration induced dose-dependent peripheral neurotoxicity. Pain perception
      and nerve conduction velocity in the tail were significantly impaired,
      particularly after the high-dose treatment. The dorsal root ganglia sensory
      neurons and, to a lesser extent, satellite cells showed the same changes as those
      induced by CDDP, mainly affecting the nucleus and nucleolus of ganglionic sensory
      neurons. Moreover, significant amounts of platinum were detected in the dorsal
      root ganglia and kidney after CBDCA treatment. CONCLUSIONS: CBDCA is neurotoxic
      in our model, and the type of pathological changes it induces are so closely
      similar to those caused by CDDP that it is probable that neurotoxicity is induced
      in the two drugs by the same mechanism. This model can be used alone or in
      combination with other drugs to explore the effect of CBDCA on the peripheral
      nervous system.

PMID- 9636838
TI  - Psoriasiform lesions as paraneoplastic manifestation in Hodgkin's disease.

PMID- 9636839
TI  - Irinotecan-induced immune thrombocytopenia.
AB  - BACKGROUND: Irinotecan is currently used as second-line chemotherapy for advanced
      colorectal cancer. We report a case of severe thrombocytopenia after Irinotecan,
      suggesting an immune mechanism, in a 53-year-old patient. PATIENTS AND METHODS:
      The patient's sera were screened for platelet antibodies with an indirect
      platelet immunofluorescence test (PIIFT). The monoclonal antibody immobilization
      of platelet antigen assay (MAIPA) was used to characterize the antibody target.
      RESULTS: We detected an IgG platelet antibody in the patient's serum in the
      presence of Irinotecan by means of PIIFT, and not in the presence of SN-38, its
      active metabolite. The specificity of the binding was asserted after CD32 MoAb
      blockade. The platelet binding site could not be strictly identified with MAIPA
      and immunoblotting but GpIIb/IIIa can be excluded after experiments with
      Glanzmann platelets. CONCLUSION: This case can be considered the first documented
      Irinotecan-induced immune thrombocytopenia.

PMID- 9636840
TI  - A phase II study of a novel gemcitabine plus cisplatin regimen administered every
      three weeks for advanced non-small-cell lung cancer.
AB  - BACKGROUND: The aim of this study was to determine the clinical activity and
      toxicity of a novel chemotherapy combination regimen of gemcitabine plus
      cisplatin, administered every three weeks, in patients with advanced non-small
      cell lung cancer (NSCLC). PATIENTS AND METHODS: Twenty-six previously untreated
      stages III (14) and IV (12) patients were included. Gemcitabine was administered
      on days 1 and 8 at a dose of 1250 mg/m2 and cisplatin was administered at a dose
      of 100 mg/m2 on day 1, every 21 days. RESULTS: Twenty-five patients were
      evaluable for response. One patient achieved a complete response, and 16 patients
      partial responses. The overall response rate was 65.3% (95% CI: 45%-82%). The
      main toxicity was hematological: neutropenia NCIC-CTC grade 3-4 in 54% of the
      patients, and thrombocytopenia grade 3-4 in 23%. The non-hematological toxicity
      was mild and tolerable. Only 13% of gemcitabine injections were dose-reduced or
      omitted due to toxicity. The actual dose-intensity of gemcitabine was 715
      mg/m2/week, and 31 mg/m2/week for cisplatin. These figures represent the 86% and
      93% of the theoretical dose intensity of both drugs, respectively. With a median
      follow-up of 10 months (range 7-13), 17 patients are still alive and nine have
      died. The median overall survival is 12 months. CONCLUSION: This novel
      combination of gemcitabine and cisplatin administered every three weeks is well
      tolerated and induces a remarkably high response rate. The regimen proves more
      interesting than the four-week schedules, particularly regarding patients who are
      candidates for local therapy.

PMID- 9636841
TI  - More on dose-intensity of anthracyclines in breast cancer.

PMID- 9636842
TI  - Actinomycosis.

PMID- 9636843
TI  - Immunomodulation for the treatment of invasive fungal infections.

PMID- 9636844
TI  - Combination immunotherapy and antifungal chemotherapy.
AB  - Historical clinical observations suggested that cellular immunity is central in
      the outcome of deep fungal infections, and experimental observations later proved
      this. Unstimulated effector cells interact synergistically with antifungal drugs.
      Recombinant cytokines, of which interferon gamma (IFN-gamma) is the most
      prominent, stimulate several host-effector cells (macrophages, monocytes,
      neutrophils) for antifungal activity. Effector cells stimulated by such molecules
      (data with macrophage colony-stimulating factor, granulocyte colony-stimulating
      factor, and granulocyte-macrophage colony-stimulating factor with azoles are
      presented as examples) also have enhanced synergistic activity with antifungals.
      A tilt toward a type 1 T-helper (Th1) cell pathway seems essential in antifungal
      host defenses. Cytokines (and anticytokines) that promote this pathway can be
      protective in vivo and act cooperatively with antifungal drugs. Observations with
      interleukin (IL)-12, IFN-gamma, and anti-IL4 illustrate this. The clinical
      applications of these strategies are just beginning.

PMID- 9636845
TI  - The potential role of cytokine therapy for fungal infections in patients with
      cancer: is recovery from neutropenia all that is needed?
AB  - Optimal regimens for the treatment of invasive fungal infections have yet to be
      defined, and these life-threatening conditions are one of the leading causes of
      treatment failure in patients with cancer. A substantial body of preclinical work
      points in the direction of using cytokines as immunomodulators of the multiple
      deficiencies involved in the progression of fungal infections in neutropenic and
      nonneutropenic cancer patients. These deficiencies include not only the easily
      recognized deficiencies in cell quantity but also subtle deficiencies of cell
      function. Four cytokines (granulocyte colony-stimulating factor, granulocyte
      macrophage colony-stimulating factor, macrophage colony-stimulating factor, and
      interferon gamma) show promise as adjuvant therapy for proven fungal infections
      in this setting, although clinical experience is still limited. As an additional
      approach, the concept of white blood cell transfusions has been revived by the
      use of granulocyte colony-stimulating factor and promises to be helpful in the
      setting of neutropenia.

PMID- 9636846
TI  - Use of macrophage colony-stimulating factor in the treatment of fungal
      infections.
AB  - Management of fungal infections is a major medical problem. The risk of
      developing a fungal infection is higher for patients who are undergoing dose
      intensive therapy, are immunocompromised, have neutropenia, are receiving
      prophylactic antibiotics, have other infections, have invasive catheters, or have
      a history of severe trauma or burns. Survival is decreased among patients who
      develop fungal infection in these situations. In view of the high morbidity and
      mortality associated with fungal infections in transplant recipients, cytokines
      that enhance cell function, such as macrophage colony-stimulating factor (M-CSF),
      have been investigated. M-CSF enhances cytotoxicity, superoxide production,
      phagocytosis, chemotaxis, and secondary cytokine production in monocytes and
      macrophages. Animal models and clinical data suggest efficacy of M-CSF in
      controlling fungal infection.

PMID- 9636847
TI  - Monocyte-macrophages, granulocyte-macrophage colony-stimulating factor, and
      prolonged survival among patients with acute myeloid leukemia and stem cell
      transplants.
AB  - Recombinant GM-CSF has been recently shown to prolong survival of elderly
      patients with acute myeloid leukemia (AML) by reducing the rate of induction
      therapy-related mortality. In a prospective, randomized, placebo-controlled,
      double-blind, multicenter study conducted by the Eastern Cooperative Oncology
      Group in the United States, granulocyte-macrophage colony-stimulating factor (GM
      CSF) was given only to those patients who had hypocellular or remission marrow on
      day 10 of one or two cycles of standard induction therapy. Although the
      administration of GM-CSF significantly reduced a wide range of adverse events,
      the main benefit of this cytokine seems to be mediated by a reduction in sepsis.
      A similarly designed study, conducted by the Southwest Oncology Group in a
      directly comparable AML patient population with use of granulocyte colony
      stimulating factor (G-CSF) as the supportive cytokine, showed no survival benefit
      and no reduction in the rates of serious or lethal sepsis. In most current
      clinical situations, GM-CSF and G-CSF are indistinguishable both in terms of
      efficacy and toxicity. GM-CSF and G-CSF have very different impacts on the
      survival of patients with AML. The stimulation of monocyte-macrophage function
      and proliferation by GM-CSF may mediate the selective benefit of GM-CSF in
      patients with AML and stem cell transplants. GM-CSF merits further study as
      therapy for and/or protection against opportunistic sepsis in patients with
      cancer and will be included in a number of International Oncology Study Group
      protocols.

PMID- 9636848
TI  - Treatment of acute myeloid leukemia with cytokines: effect on duration of
      neutropenia and response to infections.
AB  - Clinical data regarding the use of colony-stimulating factors for the treatment
      of acute myeloid leukemia (AML) are conflicting because of varying study
      conditions. Interpretation of data is affected by differences in patients' ages,
      induction regimens, the timing of growth factor administration, the presence of
      marrow hypoplasia, disease states, differences in the products used, and
      statistical endpoints. Most trials of granulocyte colony-stimulating factor (GM
      CSF) have demonstrated a significant shortening of neutrophil recovery time and a
      trend toward higher rates of complete remission. Several studies have
      demonstrated a significant reduction in the rates of morbidity or early mortality
      with G-CSF or GM-CSF. In vitro data support the concept of enhancing
      antimicrobial activity with macrophage colony-stimulating factor or GM-CSF. The
      safety and potential benefit of these cytokines suggest that cytokines should be
      administered to patients receiving induction therapy for AML who are at high risk
      for therapy-related morbidity and mortality.

PMID- 9636849
TI  - Photo quiz. I. Reactive hemophagocytic syndrome caused by CMV infection.

PMID- 9636850
TI  - Characterization of Bartonella henselae isolated from bacillary angiomatosis
      lesions in a human immunodeficiency virus-infected patient in Germany.
AB  - Infections with Bartonella (Rochalimaea) henselae can result in a variety of
      clinical entities, including bacillary angiomatosis in immunocompromised hosts.
      The fastidious nature of this bacterium has so far prevented the culture of many
      clinical isolates. We report the recovery of the first European B. henselae
      isolate associated with bacillary angiomatosis. The isolate was cultured in a
      frozen skin biopsy specimen from a human immunodeficiency virus (HIV)-infected
      patient and was characterized by means of biochemical, bacteriologic,
      immunologic, and molecular biological methods including pulsed-field gel
      electrophoresis. This strain was compared with two B. henselae strains isolated
      in the United States to determine the relationship between the isolates. We found
      that it was phenotypically and genotypically indiscernible from B. henselae
      Houston-1, a blood culture isolate from an HIV-infected patient in Houston. These
      data suggest that one B. henselae clone is associated with human infections in
      Europe and the United States.

PMID- 9636851
TI  - Are all Bartonella henselae strains created equal?

PMID- 9636852
TI  - Staphylococcus aureus prosthetic valve endocarditis: optimal management and risk
      factors for death.
AB  - The mortality rate associated with Staphylococcus aureus prosthetic valve
      endocarditis (PVE) remains high. To identify clinical events associated with an
      increased risk of death among patients with S. aureus PVE and to evaluate the
      role of valve replacement surgery in reducing mortality, we conducted a
      retrospective cohort study of patients who met strict criteria for definite S.
      aureus PVE. The primary endpoint for the study was survival at 3 months from the
      date of diagnosis. S. aureus PVE was diagnosed in 33 patients. Of these, 14 (42%)
      died within 90 days of the diagnosis. Cardiac complications were detected in 22
      (67%), and central nervous system (CNS) complications were detected in 11 (33%).
      A stepwise logistic regression multivariate model demonstrated that cardiac
      complications, but not CNS complications, were associated with increased
      mortality and that performing valve replacement surgery during antibiotic therapy
      was associated with decreased mortality. These associations were confirmed by
      using a Cox proportional hazards model with time-dependent covariates to control
      for survival bias. Performing valve replacement surgery during antimicrobial
      therapy will reduce the mortality among patients with S. aureus PVE, even those
      without evidence of cardiac complications.

PMID- 9636853
TI  - The role of valve replacement in the treatment of prosthetic valve endocarditis.

PMID- 9636854
TI  - Once-daily sparfloxacin versus high-dosage amoxicillin in the treatment of
      community-acquired, suspected pneumococcal pneumonia in adults. Sparfloxacin
      European Study Group.
AB  - The objective of this randomized, double-blind, multicenter study of 329 adult
      patients requiring hospitalization was to compare the safety and efficacy of
      sparfloxacin at a dosage of 200 mg once daily (following a 400-mg loading dose on
      day 1) with those of amoxicillin given as a 1-g oral dose three times daily for
      treatment of community-acquired pneumonia suspected to be due to Streptococcus
      pneumoniae. Success of treatment was determined by a combination of clinical
      assessment and chest radiography. Pneumococcal pneumonia was the confirmed
      diagnosis for 177 patients (54%). Overall rates of success among evaluable
      patients were equivalent between drugs, both at the end of treatment
      (sparfloxacin, 92%; amoxicillin, 87%) and at follow-up (sparfloxacin, 89%;
      amoxicillin, 84%). Sparfloxacin was well-tolerated and produced fewer
      gastrointestinal effects than amoxicillin. In conclusion, sparfloxacin is a safe
      and effective alternative to high-dose amoxicillin for the treatment of suspected
      pneumococcal community-acquired pneumonia.

PMID- 9636855
TI  - Photo quiz. II. Disseminated histoplasmosis.

PMID- 9636856
TI  - A new fluoroquinolone for community-acquired pneumonia.

PMID- 9636858
TI  - Comparison of two methods for the assessment of delayed-type hypersensitivity
      skin responses in patients with human immunodeficiency virus infection.
AB  - We compared two techniques for detecting delayed-type hypersensitivity (DTH) skin
      responses in 359 patients infected with human immunodeficiency virus (HIV) (mean
      CD4+ lymphocyte count, 387/microL). DTH responses were assessed with use of two
      antigenic panels administered simultaneously: tuberculin purified protein
      derivative (PPD) plus three control antigens (Candida albicans, mumps antigen,
      and tetanus toxoid) administered by the Mantoux method and by a multiple-puncture
      device delivering seven antigens percutaneously (MULTITEST CMI; Institut Merieux,
      Lyon, France). Eighty-three patients (23%) were anergic, 216 (60%) reacted to
      both panels, 55 (15%) did not react to MULTITEST CMI but did react to the
      antigens administered by Mantoux method, and only five (1%) reacted to MULTITEST
      CMI without reacting to antigens administered by the Mantoux method (P < .001,
      McNemar's test). Each of the three possible combinations of PPD plus two control
      antigens administered by the Mantoux method were also superior to MULTITEST CMI
      for classifying patients as nonanergic (P < .001, McNemar's test). We conclude
      that the application of antigens by the Mantoux method is more efficient than
      MULTITEST CMI for detecting DTH skin responses in HIV-infected patients.

PMID- 9636857
TI  - Prophylactic effect of bovine anti-Cryptosporidium hyperimmune colostrum
      immunoglobulin in healthy volunteers challenged with Cryptosporidium parvum.
AB  - Bovine hyperimmune anti-Cryptosporidium colostrum immunoglobulin (BACI) decreases
      the intensity of Cryptosporidium parvum infection in vitro. We investigated the
      prophylactic effect of BACI in healthy adults challenged with C. parvum. After we
      established an oocyst dose that resulted in 100% infection in four volunteers
      (baseline group), 16 volunteers were randomized to receive (1) BACI prior to C.
      parvum challenge (BACI group) and a nonfat milk placebo 30 minutes later, (2)
      BACI prior to and 30 minutes after challenge (reinforced BACI group), or (3)
      nonfat milk placebo prior to and 30 minutes after challenge. Subjects received
      BACI (10 g) or nonfat milk placebo three times a day for a total of 5 days and
      were followed for clinical symptoms and oocyst excretion for 30 days. A trend
      toward less diarrhea (P = .08) was observed for subjects receiving BACI in
      comparison with occurrences in placebo recipients. Subjects receiving BACI or
      nonfat milk placebo had a 100-fold reduction in oocyst excretion as compared with
      excretion in the baseline group.

PMID- 9636859
TI  - Chronic follicular conjunctivitis associated with Chlamydia psittaci or Chlamydia
      pneumoniae.
AB  - We determined whether patients with chronic conjunctivitis in whom direct
      fluorescent antibody (DFA) tests revealed genus-specific chlamydial antigens (but
      not species-specific Chlamydia trachomatis antigens) were infected with Chlamydia
      psittaci or Chlamydia pneumoniae. Patients were divided into a case group of
      possible non-trachomatis chlamydial conjunctivitis and a control group of
      nonchlamydial conjunctivitis on the basis of examination and DFA testing. Species
      specific primers were used to amplify C. trachomatis, C. psittaci, and C.
      pneumoniae DNA with polymerase chain reaction (PCR). Four (27%) of 15 samples
      from the case group were positive for C. psittaci or C. pneumoniae DNA, whereas
      none of 24 control samples were positive. Sequencing revealed a C. pneumoniae, an
      avian C. psittaci, and two mammalian C. psittaci strains. A short course of oral
      antibiotic treatment appears to be inadequate for patients with non-trachomatis
      chlamydial conjunctivitis. Ocular infections due to C. pneumoniae and C. psittaci
      may be more common than previously recognized and can be identified by DFA and
      PCR.

PMID- 9636860
TI  - Why have group A streptococci remained susceptible to penicillin? Report on a
      symposium.
AB  - In spite of 50 years of extensive use of penicillin, group A streptococci remain
      exquisitely susceptible to this antibiotic. This observation that continuing
      susceptibility has occurred despite the development of resistance to other
      antimicrobial agents prompted a day-long meeting at Rockefeller University (New
      York) in October 1996. Among the most likely explanations for this remarkable
      state of continued susceptibility to penicillin are that beta-lactamase may not
      be expressed or may be toxic to the organism and/or that low-affinity penicillin
      binding proteins either are not expressed or render organisms nonviable. Other
      potential explanations are that circumstances favorable for the development of
      resistance have not yet occurred and/or that there are inefficient mechanisms for
      or barriers to genetic transfer. Recommended future actions include (1)
      additional laboratory investigations of gene transfer, penicillin-binding
      proteins, virulence factors, and homeologous recombination and mismatch repair;
      (2) increased surveillance for the development of penicillin resistance; (3)
      application of bioinformatics to analyze streptococcal genome sequences; and (4)
      development of vaccines and novel antimicrobial agents. Thus far the
      susceptibility of group A streptococci to penicillin has not been a major
      clinical or epidemiological problem. A similar observation, however, could have
      been made decades ago about Streptococcus pneumoniae. It is therefore vital for
      the scientific community to closely examine why penicillin has remained uniformly
      highly active against group A streptococci in order to maintain this desirable
      state.

PMID- 9636861
TI  - Clinical outcome of invasive infections by penicillin-resistant Streptococcus
      pneumoniae in Korean children.
AB  - One hundred six cases of invasive pneumococcal infections diagnosed from 1985 to
      1996 were analyzed retrospectively. The types of infection were bacteremia
      without focus (45%), meningitis (19%), peritonitis (17%), pneumonia (bacteremic)
      (16%), and others (3%). Penicillin-nonsusceptible Streptococcus pneumoniae was
      first detected in 1989, and its incidence increased rapidly thereafter, reaching
      89% in 1995. Initial empirical regimens were of parenteral beta-lactam
      antimicrobials with or without an aminoglycoside, but these were modified
      subsequently. Among the 72 nonmeningeal infections analyzed, a favorable response
      at 72 hours and death were observed in 83% and 2.5%, respectively, of 40
      penicillin-susceptible infections, as compared with 86% (P = 1.0) and 7.1% (P =
      .45) of 14 infections due to intermediate strains and 61% (P = .07) and 11% (P =
      .22) of 18 due to resistant strains. The favorable-response rate and mortality
      among 49 patients not in initially critical condition were 92% and zero,
      respectively, as compared with 52% (P = .00027) and 17% (P = .008) of 23 in
      critical condition. The data suggest that clinical outcome of penicillin
      nonsusceptible pneumococcal infection outside the CNS may be more closely related
      to clinical condition at presentation than to the level of resistance of the
      causative strain when such infection is treated with parenteral beta-lactams.

PMID- 9636862
TI  - Invasive Streptococcus pneumoniae infection in Latin American children: results
      of the Pan American Health Organization Surveillance Study.
AB  - Protein-polysaccharide conjugate vaccines against Streptococcus pneumoniae
      promise to be an effective public health intervention for children, especially in
      an era of increasing antimicrobial resistance. To characterize the distribution
      of capsular types in Latin America, surveillance for invasive pneumococcal
      infection in children < or = 5 years of age was done in six countries between
      February 1993 and April 1996. Fifty percent of 1,649 sterile-site isolates were
      from children with pneumonia, and 52% were isolated from blood. The 15 most
      common of the capsular types prevalent throughout the region accounted for 87.7%
      of all isolates. Overall, 24.9% of isolates had diminished susceptibility to
      penicillin: 16.7% had intermediate resistance and 8.3% had high-level resistance.
      Three customized vaccine formulas containing 7, 12, and 15 capsular types were
      found to have regional coverages of 72%, 85%, and 88%, respectively. This study
      emphasizes the need for local surveillance for invasive pneumococcal disease
      prior to the development and evaluation of protein-polysaccharide conjugate
      vaccines for children.

PMID- 9636863
TI  - Combination therapy with fluconazole and flucytosine for cryptococcal meningitis
      in Ugandan patients with AIDS.
AB  - We performed a randomized trial in which combination therapy with fluconazole and
      short-term flucytosine was compared with fluconazole monotherapy in 58 patients
      with AIDS-associated cryptococcal meningitis (CM). Thirty of these patients were
      randomized to receive combination therapy with fluconazole, 200 mg once a day for
      2 months, and flucytosine, 150 mg/(kg.d) for the first 2 weeks, and 28 were
      randomized to receive monotherapy with fluconazole at the same dose for 2 months.
      Patients in both groups who survived for 2 months received fluconazole as
      maintenance therapy at a dose of 200 mg three times per week for 4 months. The
      combination therapy prevented death within 2 weeks and significantly increased
      the survival rate among these patients (32%) at 6 months over that among patients
      receiving monotherapy (12%) (P = .022). The combination therapy also resulted in
      a significant decrease in the severity of headache after 1 month of treatment,
      compared with monotherapy (P = .005). No serious adverse reactions were observed
      in patients receiving either regimen. These data indicate that treatment with
      fluconazole and short-term flucytosine is a cost-effective and safe regimen that
      improves the quality of life for patients with AIDS-associated CM in developing
      countries where human immunodeficiency virus is endemic.

PMID- 9636864
TI  - Reflections on studies in developing countries.

PMID- 9636865
TI  - A double-blind comparison of itraconazole oral solution and fluconazole capsules
      for the treatment of oropharyngeal candidiasis in patients with AIDS.
AB  - This double-blind trial compared the clinical and mycological efficacy and safety
      of itraconazole oral solution with those of fluconazole capsules in the treatment
      of oropharyngeal candidiasis in patients with AIDS. A total of 244 patients were
      enrolled and randomized to one of three groups for treatment with itraconazole
      oral solution (100 mg twice daily for 7 days or 100 mg once daily for 14 days) or
      fluconazole capsules (100 mg once daily for 14 days). Among 194 evaluable cases,
      complete response (clearance of all symptoms and signs) or marked improvement was
      noted in 54 of 60 patients (90%) receiving once-daily itraconazole and in 65 of
      72 fluconazole-treated patients (90%) at the end of treatment; these results were
      statistically equivalent (P = .0024). Twice-daily itraconazole produced a
      clinical response in 51 of 62 patients (82%). The groups were equivalent in terms
      of early relapse (within the 18-day period studied); 37% of patients in the twice
      daily itraconazole group, 35% in the once-daily itraconazole group, and 34% in
      the fluconazole group relapsed. Drug tolerability was comparable between the
      three groups. These results show that, in the treatment of oropharyngeal
      candidiasis, itraconazole oral solution and fluconazole capsules at a 100-mg
      single daily dose for 14 days are equally effective.

PMID- 9636866
TI  - An outbreak of Pontiac fever among children following use of a whirlpool.
AB  - We investigated an outbreak of fever, most likely due to a contaminated
      whirlpool, among nine adults and six children residing in a summerhouse. The
      outbreak was characterized by a high attack rate, short incubation periods,
      influenza-like symptoms, and rapid recoveries, all features typical of Pontiac
      fever. However, the children had less-characteristic symptoms than the adults,
      and they did not have any sequelae. Findings on the children's chest radiographs
      were unremarkable, and none of the children had leukocytosis. Evidence of
      Legionella pneumophila infection was found in six cases: in one case by isolation
      of L. pneumophila serogroup 1 and detection of legionellae by PCR, and in five
      cases by seroconversion to the clinical isolate. Six additional cases had
      presumptive evidence of legionella infection, with seroconversion to Legionella
      micdadei antigen; a PCR assay was also positive for legionellae for one of these
      cases. In contrast, two adult nonusers of the whirlpool had no symptoms and no
      serological evidence of infection. Serological testing and cultures for other
      pathogens, as well as cultures of all environmental samples, were negative. This
      investigation demonstrates the differences between adults and children with
      respect to the clinical picture of Pontiac fever; furthermore, it shows that
      culture and PCR assay of tracheal aspirates for legionellae can be performed in a
      hospital setting for rapid diagnosis, although the sensitivities of these methods
      are low.

PMID- 9636867
TI  - Gamma knife radiosurgery and albendazole for cerebral alveolar hydatid disease.
AB  - Standard treatment of cerebral alveolar hydatid disease consists of open brain
      surgery and systemic albendazole. We describe a patient with inoperable cerebral
      alveolar hydatid cysts on whom gamma knife radiosurgery was used instead of open
      brain surgery. Because of the size of the multicystic lesion, the gamma knife
      procedure was done in two sessions. Repeated courses of albendazole were given
      concurrently. Magnetic resonance imaging follow-up studies showed marked
      shrinkage of the irradiated cystic structures and initially increased perifocal
      edema. At a follow-up visit 3 years after gamma knife radiosurgery, the
      polycystic lesion, the perifocal edema, and the neurological symptoms had all
      markedly decreased. The patient is now stable and has minimal neurological
      symptoms, and the quality of her life has improved. Gamma knife radiosurgery may
      be an alternative for patients with cerebral alveolar hydatid disease for whom
      surgery is not possible.

PMID- 9636868
TI  - Amphotericin B lipid complex for invasive fungal infections: analysis of safety
      and efficacy in 556 cases.
AB  - The safety and antifungal efficacy of amphotericin B lipid complex (ABLC) were
      evaluated in 556 cases of invasive fungal infection treated through an open
      label, single-patient, emergency-use study of patients who were refractory to or
      intolerant of conventional antifungal therapy. All 556 treatment episodes were
      evaluable for safety. During the course of ABLC therapy, serum creatinine levels
      significantly decreased from baseline (P < .02). Among 162 patients with serum
      creatinine values > or = 2.5 mg/dL at the start of ABLC therapy (baseline), the
      mean serum creatinine value decreased significantly from the first week through
      the sixth week (P < or = .0003). Among the 291 mycologically confirmed cases
      evaluable for therapeutic response, there was a complete or partial response to
      ABLC in 167 (57%), including 42% (55) of 130 cases of aspergillosis, 67% (28) of
      42 cases of disseminated candidiasis, 71% (17) of 24 cases of zygomycosis, and
      82% (9) of 11 cases of fusariosis. Response rates varied according to the pattern
      of invasive fungal infection, underlying condition, and reason for enrollment
      (intolerance versus progressive infection). These findings support the use of
      ABLC in the treatment of invasive fungal infections in patients who are
      intolerant of or refractory to conventional antifungal therapy.

PMID- 9636869
TI  - Rapid simultaneous diagnosis of infections with respiratory syncytial viruses A
      and B, influenza viruses A and B, and human parainfluenza virus types 1, 2, and 3
      by multiplex quantitative reverse transcription-polymerase chain reaction-enzyme
      hybridization assay (Hexaplex).
AB  - A multiplex quantitative reverse transcription-polymerase chain reaction-enzyme
      hybridization assay (Hexaplex; Prodesse, Milwaukee) was developed and used to
      rapidly detect and quantitate RNA of respiratory syncytial viruses A and B,
      influenza viruses A and B, and human parainfluenza virus types 1, 2, and 3 in
      nasal wash specimens in a single test. Primers and probes originated from highly
      conserved regions of each viral genome. Six and a half primer pairs were mixed
      for the simultaneous detection and quantitation of RNA from seven different
      respiratory viruses. We tested 109 clinical samples with this assay. Twenty-nine
      virus culture-positive samples were all positive by Hexaplex. Samples from 40
      symptomatic patients were negative by virus culture, but eight of these were
      positive by Hexaplex. Forty samples from asymptomatic children were negative by
      both virus culture and Hexaplex. No cross-reactions were noted among 17 different
      respiratory viruses with use of this assay. Hexaplex was 100% sensitive (95%
      confidence interval [CI], 0.88-1.0) and 98% specific (95% CI, 0.97-0.99). All
      eight "false-positive" Hexaplex results (in comparison with negative viral
      culture results) were for symptomatic patients with low numbers of virus RNA
      copies. This finding suggests that Hexaplex may be more sensitive than virus
      culture. Our data demonstrate that Hexaplex is a rapid, sensitive, and specific
      quantitative test for the diagnosis of infections with these seven common
      respiratory viruses.

PMID- 9636870
TI  - Disseminated sporotrichosis and Sporothrix schenckii fungemia as the initial
      presentation of human immunodeficiency virus infection.
AB  - Infection with Sporothrix schenckii causes a localized lymphocutaneous disease in
      the immunocompetent host, while it frequently results in disseminated disease in
      the immunocompromised patient. There are a growing number of reports of S.
      schenckii infection in the human immunodeficiency virus (HIV)-infected
      population, where the disease usually starts as a localized cutaneous lesion and
      subsequently disseminates. The optimal treatment of systemic sporotrichosis in
      HIV-positive patients is as yet unknown. This article presents a case report of
      disseminated sporotrichosis in an HIV-infected patient, a review of the
      literature, and discussion of treatment options for HIV-infected patients.

PMID- 9636871
TI  - Comparison of serum galactomannan antigen detection and competitive polymerase
      chain reaction for diagnosing invasive aspergillosis.
AB  - To improve the diagnosis of invasive aspergillosis (IA), we retrospectively
      compared competitive polymerase chain reaction (PCR) and sandwich ELISA for
      detection of serum galactomannan (GM) antigen. We studied 281 serum samples
      collected weekly during the period at risk for IA from 41 selected hematology
      patients. Twenty-two patients had confirmed, probable, or suspected IA, according
      to clinical and mycologic data. Fifteen of them had positive GM titers (87
      samples) and 12 had positive PCRs (20 samples). Nineteen of the 20 PCR-positive
      samples were also GM-positive. Of the 19 patients without IA (83 samples), one
      had 3 GM-false-positive samples. Neither test anticipated the initiation of
      antifungal therapy on the basis of clinical suspicion. Both tests were more
      likely to be positive before death. This study suggests that PCR on serum samples
      is not more sensitive than GM detection. However, PCR can improve the specificity
      of the GM test. Together, these noninvasive tests should improve the diagnosis of
      IA.

PMID- 9636872
TI  - Clinical significance and outcome of anaerobic bacteremia.
AB  - We retrospectively studied the incidence of anaerobic bacteremia during 6 years
      (1991-1996) at Turku University Central Hospital (Turku, Finland). The clinical
      significance of a positive anaerobic blood culture, the effect of a positive
      culture on the choice of antimicrobial therapy, and the outcome for patients were
      evaluated. Cultures of blood from 81 patients yielded anaerobic bacteria (4% of
      all bacteremias). Anaerobic bacteremia was clinically significant in 57 patients
      (0.18 cases per 1,000 admissions). Only half (28) of these patients received
      appropriate and effective antimicrobial treatment before the results of blood
      cultures were reported; for 18 patients (32%), initially ineffective treatment
      was changed on the basis of the bacteriologic results, and for 11 patients (19%),
      the treatment was not changed. The mortality in these patient groups was 18%,
      17%, and 55%, respectively. Empirical therapy may provide coverage for anaerobes
      in only half of the patients with anaerobic bacteremia, and failure to pay
      attention to the results of anaerobic blood cultures may have serious
      consequences for patients.

PMID- 9636873
TI  - Common emergence of amantadine- and rimantadine-resistant influenza A viruses in
      symptomatic immunocompromised adults.
AB  - The importance and significance of amantadine- or rimantadine-resistant influenza
      viruses in immunocompromised patients was studied in a population of adult bone
      marrow transplant (BMT) recipients and patients with leukemia prospectively
      cultured for respiratory viruses. Influenza A viruses were isolated from 29
      patients with acute respiratory illness (14 BMT recipients and 15 patients with
      leukemia). Fifteen patients (52%) received amantadine (n = 4) or rimantadine (n =
      11) therapy. All influenza isolates recovered from six patients shedding virus
      for > or = 3 days were screened for antiviral susceptibility; resistant isolates
      were further genetically characterized. Initial influenza isolates were
      susceptible to amantadine or rimantadine, but subsequent isolates from five of
      six patients were resistant. Influenza-associated mortality was similar among
      patients with and without documented antiviral resistance (2 of 5 vs. 5 of 24).
      We conclude that development of antiviral resistance in immunocompromised
      individuals should be considered when they have been treated with antivirals and
      have shed influenza virus for a prolonged period. Isolation procedures should be
      instituted for all immunocompromised patients with influenza, both during and
      after therapy with amantadine or rimantadine.

PMID- 9636874
TI  - Detection of chlamydiosis in a shipment of pet birds, leading to recognition of
      an outbreak of clinically mild psittacosis in humans.
AB  - Avian chlamydiosis was detected in a shipment of > 700 pet birds from a Florida
      bird distributor that were sold to nine Atlanta-area pet stores in August 1995.
      Respiratory illness among persons who had recently acquired birds from this
      shipment was reported to local public health officials. The attack rate of acute
      respiratory illness was 10.7% among persons in households exposed to birds from
      the implicated flock vs. 1.8% among control households (odds ratio, 6.60; 95%
      confidence interval, 1.39-31.2). Illness and serological evidence of infection in
      the absence of symptoms were more common among persons in households with
      recently purchased birds that were sick or that had died and among persons who
      had had direct contact with the birds. Clinical psittacosis or serological
      evidence of Chlamydia psittaci infection was found in 30.7% of households with
      birds from the infected flock. Mild illnesses and asymptomatic infections in
      exposed persons were unusual features of this outbreak.

PMID- 9636875
TI  - Rhinocerebral mucormycosis treated with amphotericin B colloidal dispersion in
      three patients.
AB  - Rhinocerebral mucormycosis (zygomycosis) primarily affects diabetic or
      immunosuppressed patients and typically progresses rapidly, necessitating
      surgical excision and antifungal therapy with amphotericin B. Large doses of
      amphotericin B are required for cure, causing significant renal toxicity.
      Amphotericin B colloidal dispersion (ABCD; Amphocil, Sequus Pharmaceuticals,
      Menlo Park, CA) is a 1:1 complex of cholesteryl sulfate and amphotericin B, which
      results in significant reduction of toxicity, especially nephrotoxicity. We
      describe three patients with life-threatening rhinocerebral mucormycosis treated
      with ABCD. All patients had high serum creatinine levels due to prior treatment
      with amphotericin B; these levels reverted to normal during treatment with ABCD.
      Two patients with diabetes mellitus were cured after receiving a combination of
      surgery and ABCD therapy. The third patient, who had myelodysplastic syndrome,
      had an initial good response, with cure of the fungal infection; however, he
      eventually died of his primary illness. To the best of our knowledge, this is the
      first detailed clinical description of the treatment of mucormycosis with ABCD.

PMID- 9636876
TI  - Primary liver abscess due to Klebsiella pneumoniae in Taiwan.
AB  - Pyogenic liver abscess is an uncommon complication of intra-abdominal or biliary
      tract infection and is usually a polymicrobial infection associated with high
      mortality and high rates of relapse. However, over the past 15 years, we have
      observed a new clinical syndrome in Taiwan: liver abscesses caused by a single
      microorganism, Klebsiella pneumoniae. We reviewed 182 cases of pyogenic liver
      abscess during the period September 1990 to June 1996; 160 of these cases were
      caused by K. pneumoniae alone, and 22 were polymicrobial. When patients with K.
      pneumoniae liver abscess were compared with those who had polymicrobial liver
      abscess, we found higher incidences of diabetes or glucose intolerance (75% vs.
      4.5%) and metastatic infections (11.9% vs. 0) and lower rates of intra-abdominal
      abnormalities (0.6% vs. 95.5%), mortality (11.3% vs. 41%), and relapse (4.4% vs.
      41%) in the former group. Liver abscess caused by K. pneumoniae is a new clinical
      syndrome that has emerged as an important infectious complication in diabetic
      patients in Taiwan.

PMID- 9636877
TI  - Something's rotten: a nosocomial outbreak of malodorous Pseudomonas aeruginosa.
AB  - From July 1994 through November 1996, a phenotypically unique strain of
      Pseudomonas aeruginosa producing a pungent, "rotten-potato" odor and a positive
      lysine decarboxylase reaction was isolated from 39 patients at UCLA Medical
      Center (Los Angeles). Most cases (95%) were in intensive care units and had
      clinical infections (72%). Most isolates (74%) were recovered from cultures of
      respiratory secretions. To determine risk factors for acquisition of the
      organism, 23 cases were compared with 23 randomly selected controls matched by
      service and isolate date. Multivariate analysis revealed that isolation of
      malodorous P. aeruginosa was associated with mechanical ventilation of > 24
      hours' duration (odds ratio [OR] = 9.4; P = .001) and transfer from an outside
      hospital (OR = 5.7; P = .04). DNA from outbreak strains hybridized to P.
      aeruginosa-specific toxin A and phospholipase C gene probes and all outbreak
      isolates tested were found to be identical by use of pulsed-field gel
      electrophoresis. An unusual phenotypic characteristic of the strain led to the
      recognition of a nosocomial outbreak of P. aeruginosa infection associated with
      mechanical ventilation.

PMID- 9636878
TI  - Molecular, serological, and clinical features of 16 consecutive cases of invasive
      streptococcal disease. Southeastern Minnesota Streptococcal Working Group.
AB  - We performed a comprehensive analysis of the molecular, serological, and clinical
      features of 16 consecutive cases of invasive streptococcal disease (ISD). The
      majority of cases were linked to two group A streptococcus (GAS) clones closely
      related by pulsed-field gel electrophoresis (PFGE) and designated as PFGE-1 and
      PFGE-1.1. These clones, serotyped as M-3, T-3/B3264, carried an allelic variant
      of the gene that encodes pyrogenic exotoxin A (speA3) and the gene that encodes
      streptococcal superantigen (SSA) but different emm alleles that encode M-protein.
      The characteristics and clinical features of patients were similar to those
      described in previous reports, regardless of the responsible GAS clone. However,
      worse clinical outcomes (shock and death) were more frequent when patients
      infected with PFGE1/1.1 clones were considered as a group and compared with all
      other patients as a group. One striking feature in some patients with deep tissue
      infection was a lack of inflammatory cells despite the presence of numerous
      streptococci. An evaluation of PFGE profiles of GAS isolated elsewhere
      demonstrated that the PFGE-1 clone has caused invasive disease in other locations
      in the United States and in Japan.

PMID- 9636879
TI  - Is prevaccination screening for hepatitis B among sexually active adolescents
      cost-effective?

PMID- 9636880
TI  - Intraventricular quinupristin/dalfopristin for the treatment of vancomycin
      resistant Enterococcus faecium shunt infection.

PMID- 9636881
TI  - Epidural abscess due to deep-neck infection.

PMID- 9636882
TI  - Retrosternal abscess: a prominent manifestation of infection due to
      Staphylococcus aureus.

PMID- 9636883
TI  - Simultaneous obstructing and pseudomembranous necrotizing tracheobronchitis due
      to Aspergillus flavus.

PMID- 9636884
TI  - Intrabiliary rupture of hepatic hydatid cysts: diagnosis by use of magnetic
      resonance cholangiography.

PMID- 9636885
TI  - Nontuberculous mycobacterial tenosynovitis: report of two cases.

PMID- 9636886
TI  - Asymptomatic Mycobacterium avium complex pneumonia complicated by infectious
      arthritis/osteomyelitis.

PMID- 9636887
TI  - Mycotic aneurysm of the ulnar artery distal to the wrist.

PMID- 9636888
TI  - Endocarditis due to Neisseria elongata subspecies nitroreducens: case report and
      review.

PMID- 9636889
TI  - Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary
      disease: report of eight cases and review.

PMID- 9636890
TI  - Two-year review of hepatitis A vaccine safety: data from the Vaccine Adverse
      Event Reporting System (VAERS).

PMID- 9636891
TI  - Cerebral pseudallescheriasis due to Pseudallescheria boydii as the first
      manifestation of AIDS.

PMID- 9636892
TI  - Isolated pleural effusion with pleural fibrosis in a patient with subacute
      progressive disseminated histoplasmosis.

PMID- 9636893
TI  - Pathogenesis of fever: are circulating pyrogenic cytokines the only mediators?

PMID- 9636894
TI  - Nosocomial infections in patients infected with human immunodeficiency virus.

PMID- 9636895
TI  - Utility of the enzyme-linked immunosorbent assay for diagnosing neurobrucellosis.

PMID- 9636896
TI  - Another case of breast hypertrophy in a patient treated with indinavir.

PMID- 9636897
TI  - Guidelines for the prevention of antimicrobial resistance in hospitals.

PMID- 9636898
TI  - Lactobacillus bacteremia and endocarditis.

PMID- 9636899
TI  - Rapid emergence of resistance to cefepime during treatment.

PMID- 9636900
TI  - Percutaneous inoculation tuberculosis.

PMID- 9636901
TI  - Cutaneous infection due to Mycobacterium gordonae in a human immunodeficiency
      virus-infected patient.

PMID- 9636902
TI  - Retrograde cerebral perfusion: is the brain really being perfused?

PMID- 9636903
TI  - Neurophysiologic effects of retrograde cerebral perfusion used for aortic
      reconstruction.
AB  - OBJECTIVE: The results of neurophysiologic monitoring using somatosensory evoked
      potentials (SSEPs) and electroencephalography (EEG) were analyzed to determine if
      retrograde cerebral perfusion (RCP) supported central nervous system electrical
      function during surgery that required temporary interruption of antegrade
      cerebral perfusion (IACP). DESIGN: A prospective, observational study. SETTING: A
      university hospital. PARTICIPANTS: Fifteen adult patients who underwent aortic
      reconstruction using RCP and three patients who underwent thoracic aortic
      operations using hypothermic circulatory arrest without RCP. INTERVENTIONS: SSEPs
      and EEG were monitored continuously throughout the operation. Regression analysis
      was performed to determine the factors that affected the rate of decrease in SSEP
      amplitudes during IACP and the time required for SSEP and EEG activity to recover
      after antegrade cerebral perfusion (ACP) was restored. MEASUREMENTS AND MAIN
      RESULTS: The amplitude of SSEPs that were elicited decreased over time after
      IACP. The mean +/- standard deviation (SD) time required for the brachial plexus
      (Erb's point), cervicomedullary junction (N13), and brainstem (N18) SSEPs to
      decrease to 0.5 of their original amplitude after IACP were 30 +/- 2, 19 +/- 2,
      and 16 +/- 2 minutes, respectively. The rate of decrease in the N18 SSEP
      amplitude after IACP correlated positively to the fraction of no-flow time (p =
      0.01). CONCLUSION: RCP attenuated the rate of decay in SSEP amplitudes during
      IACP. This suggested that RCP had a measurable physiologic effect on central
      nervous system function and may increase the time that ACP can be safely
      interrupted.

PMID- 9636904
TI  - Anesthesia for deep hypothermic circulatory arrest in adults: experience with the
      first 50 patients.
AB  - OBJECTIVE: To evaluate the efficacy of a simple method of central nervous system
      (CNS) protection in patients undergoing deep hypothermic circulatory arrest
      (DHCA) lasting less than 30 minutes, for a variety of complex cardiovascular
      procedures. DESIGN: A retrospective case review. SETTING: A university teaching
      hospital. PARTICIPANTS: Fifty consecutive patients (25 women, 25 men) undergoing
      elective or emergency cardiovascular operations requiring DHCA between August
      1991 and December 1996. INTERVENTIONS: Patients underwent DHCA for a variety of
      surgical procedures. Neurologic protection was with thiopental, ice packs to the
      head, and systemic core hypothermia to a nasopharyngeal temperature (NPT) of 18
      degrees to 20 degrees C. MEASUREMENTS AND MAIN RESULTS: The mean duration of
      circulatory arrest was 18 +/- 10 minutes (range, 5 to 42 minutes). The mean NPT
      at time of arrest was 18.7 degrees +/- 1.7 degrees C. Three patients (6%) had
      gross CNS morbidity, one of whom died. The circulatory arrest times for these
      three patients were 8, 39, and 40 minutes. Perioperative mortality was 8% (n =
      4). The circulatory arrest times for the patients who died were 12, 13, 23, and
      39 minutes. CONCLUSION: The anesthetic management of DHCA described is simple,
      effective, and safe, and can be performed in any institution that performs
      cardiac surgery.

PMID- 9636905
TI  - Effect of aortic cannula characteristics and blood velocity on transcranial
      doppler-detected microemboli during cardiopulmonary bypass.
AB  - OBJECTIVES: Cerebral microemboli are responsible to a large extent for the
      neuropsychiatric deficits after cardiac surgery. Differences in cannula size
      during cardiopulmonary bypass (CPB) will result in different velocities of blood
      exiting the aortic cannula. This study determined whether the number of
      transcranial Doppler (TCD)-detected emboli in the middle cerebral artery (MCA)
      during CPB correlated with blood speed or the direction of flow as determined by
      the shape of the aortic cannula. DESIGN: Patients were studied prospectively for
      evidence of TCD-detected emboli. If patients met the inclusion criteria, the
      choice of cannula was determined by surgical preference. SETTING: All studies
      were conducted at a single tertiary care academic cardiac surgery hospital by a
      single observer. PARTICIPANTS: Thirty-two patients undergoing first-time elective
      aortocoronary bypass surgery who were free of neurologic dysfunction or
      peripheral vascular disease and weighed 60 to 85 kg were studied. Patients who
      had other concurrent cardiac operations or who were in cardiogenic shock were
      excluded. INTERVENTIONS: Three aortic cannula types for elective aortocoronary
      bypass surgery were used: 24F curved (n = 19), 24F straight (n = 6), and 22F
      straight (n = 7), with internal diameters (IDs) of 7.2, 6.6, and 5.9 mm,
      respectively. TCD-detected emboli were identified in the MCA. MEASUREMENTS AND
      MAIN RESULTS: The rate of TCD-detected emboli (0.02 to 11.4 emboli per minute)
      was not related to the velocity of blood (46 to 77 cm/s) and was not affected by
      the choice of either a straight or curved aortic cannula. CONCLUSIONS: The choice
      of a straight or curved aortic cannula or of a 24F versus 22F cannula may not be
      important with respect to the number of cerebral microemboli.

PMID- 9636906
TI  - Cerebral complications after coronary artery bypass and heart valve surgery: risk
      factors and onset of symptoms.
AB  - OBJECTIVES: Cerebral complications continue to be a major cause of morbidity
      after cardiac surgery. Earlier studies have mainly focused on intraoperative
      events, but symptoms may also occur later in the postoperative period. The
      purpose of this study was to determine the incidence and risk factors of focal
      neurologic complications and timing of cerebral symptoms. DESIGN: A retrospective
      study. SETTING: Linkoping University Hospital. PARTICIPANTS: Two thousand four
      hundred eighty patients who underwent cardiac surgery from 1992 to 1995.
      INTERVENTIONS: Standard cardiopulmonary bypass (CPB) technique was used in all
      patients. Anticoagulant treatment included heparin and patients with coronary
      artery surgery were also administered acetylsalicylic acid and valve-surgery
      patients received warfarin or dicumarol. MEASUREMENTS AND MAIN RESULTS: Seventy
      five patients (3%) had focal neurologic deficits and/or confusion
      postoperatively. In 32 patients (43%), the onset was not intraoperative but
      occurred later in the postoperative period. The lowest incidence of cerebral
      complications was found in patients who underwent single-valve replacement (1.2%)
      and the highest incidence was found in patients who underwent combined procedures
      (valve and coronary artery surgery; 7.6%). Patients greater than 70 years of age
      had a complication rate of 4.1% compared with 2.5% in patients aged 70 years and
      less (p < 0.05). The incidence of diabetes mellitus was 11.4% in the entire
      series, but was more common (18.7%; p < 0.05) in patients with cerebral symptoms.
      Also, 5.9% of all patients had a history of cerebrovascular disease compared with
      14.7% (p < 0.01) of patients with cerebral complications. CONCLUSION: Cerebral
      complications may be delayed after cardiac surgery, suggesting causes of cerebral
      damage other than intraoperative events. Valve-surgery patients had the lowest
      incidence and patients with combined procedures had the highest incidence of
      cerebral complications. Advanced age, diabetes mellitus, and preexisting
      cerebrovascular disease increased the risk.

PMID- 9636907
TI  - Intraoperative transesophageal echocardiography during noncardiac surgery.
AB  - OBJECTIVE: To investigate the use and impact of transesophageal echocardiography
      (TEE) during noncardiac surgery. DESIGN: Retrospective study. SETTING: A
      university teaching hospital. PARTICIPANTS AND INTERVENTIONS: The medical records
      and the videotapes of 123 intraoperative TEE examinations were reviewed.
      MEASUREMENTS AND MAIN RESULTS: TEE was used for non-consultative indications in
      68 patients and in consultation in 55 patients. Information that would not have
      been detected intraoperatively by other means included intracardiac defects,
      valvular and aortic pathology, the presence or absence of ventricular dysfunction
      or intracardiac thrombi, and embolization during surgery. Findings during the
      initial TEE examination and the TEE evaluation of intraoperative events resulted
      in a major impact on patient management in 15% of patients. The majority of
      patients in whom TEE had any impact (the sum of major, minor, and limited impact
      groups) were classified as American Society of Anesthesiologists (ASA) class 3 or
      4. Patients in whom TEE had any impact were significantly older than patients in
      whom TEE had no impact (66.5 +/- 13.4 years v 58.1 +/- 16.2 years; p < 0.05). No
      patient experienced a complication related to intraoperative TEE. CONCLUSION: It
      appears that TEE in patients undergoing noncardiac surgery is efficacious in
      rapidly disclosing new findings and information during periods of hemodynamic
      instability. It may have a significant impact on intraoperative patient
      management and may be beneficial in patients older than 66 years of age.

PMID- 9636908
TI  - Simultaneous transesophageal atrial pacing and transesophageal echocardiography
      in cardiac surgical patients.
AB  - OBJECTIVES: To measure the effect of inserting a transesophageal echocardiography
      (TEE) probe on the pacing threshold of a previously inserted transesophageal
      pacing stethoscope, and to examine whether an indwelling pacing stethoscope
      influences the feasibility and image quality of a TEE examination. DESIGN:
      Prospective, open study using each patient as his/her own control. SETTING:
      Cardiac operating room of an academic medical center. PARTICIPANTS: Twenty adult
      patients in sinus rhythm and anesthetized for cardiac surgery. INTERVENTIONS:
      After induction of anesthesia and endotracheal intubation, a pacing stethoscope
      was inserted into the esophagus. A 5-MHz TEE probe was inserted to the four
      chamber-view position. A full echocardiographic examination was performed, noting
      image quality, ease of probe manipulation, and loss of pacing. The pacing
      stethoscope was removed, and image quality assessed again. MEASUREMENTS AND MAIN
      RESULTS: The initial mean pacing threshold +/- 1 standard deviation (SD) was 19
      +/- 8 mA (range, 10 to 37 mA). After placement of the echocardiography probe, the
      mean threshold had increased to 24 +/- 8 mA (range, 11 to 40 mA; p < 0.01). Loss
      of pacing with probe manipulation was noted in 15 of 20 patients (transient in 10
      patients, permanent in 5 patients). Problems manipulating the probe because of
      sticking to the pacing stethoscope were noted in 10 of 20 patients. Poor image
      quality, resolving after stethoscope removal, was seen in two patients.
      CONCLUSION: Placement of a TEE probe results in a modest increase of the
      transesophageal pacing threshold. An indwelling pacing stethoscope frequently
      interferes with the ability to perform a full echocardiographic examination, and
      probe manipulation commonly causes loss of pacing.

PMID- 9636909
TI  - Short atrioventricular delay dual-chamber pacing early after coronary artery
      bypass grafting in patients with poor left ventricular function.
AB  - OBJECTIVE: To investigate the effect of short atrioventricular (AV) delay dual
      chamber pacing on mean arterial pressure (MAP) and stroke volume index (SVI) in
      patients with poor left ventricular (LV) function after cardiac surgery. DESIGN:
      A prospective study. SETTING: A university hospital, single-center study.
      PARTICIPANTS: The study group consisted of 20 patients aged 63 +/- 9 years with a
      left ventricular ejection fraction (LVEF) less than 30%. The control group
      consisted of 20 patients aged 61 +/- 10 years, with an LVEF greater than 50%.
      INTERVENTIONS: Immediately after routine coronary artery bypass grafting (CABG)
      the AV delay was shortened from 160 to 40 milliseconds in atrial-paced (DDD) mode
      and from 100 to 40 milliseconds in atrial-sensed ventricular stimulation (VDD)
      mode. MAP was on-line monitored and SVI was calculated by thermodilution. In one
      patient with an LVEF of 18% (case study), transmitral flow velocity and LV
      isovolumetric relaxation time were assessed using Doppler echocardiography during
      VDD pacing at 40-, 80-, and 120-millisecond AV delay. RESULTS: Short-AV delay DDD
      pacing decreased MAP in the control group (84.3 +/- 9 v 75.7 +/- 9 mmHg; p <
      0.05) and SVI in both groups (study group, 35.9 +/- 7 v 31.7 +/- 7 mL/m2; control
      group, 35.3 +/- 6 v 31.0 +/- 6 mL/m2; p < 0.05). Shortening the AV delay had no
      influence on MAP and SVI during VDD pacing. During the echocardiographic case
      study, AV delay shortening distinctly modified ventricular filling patterns.
      Optimal LV filling and transmitral flow were achieved with an intermediate AV
      delay of 80 milliseconds. CONCLUSION: Dual-chamber pacing with nonphysiologic
      short AV delay failed to improve acute hemodynamics in patients with poor LV
      function after CABG. Short AV delay VDD pacing was superior to DDD pacing in both
      normal and impaired LV function. The use of Doppler echocardiography enabled
      optimization of the AV delay on the basis of LV filling patterns.

PMID- 9636910
TI  - Cardiac troponin I in diagnosis of perioperative myocardial infarction after
      cardiac surgery.
AB  - OBJECTIVE: The diagnosis of perioperative myocardial infarction (PMI) after
      cardiac surgery remains an important issue. The present study was designed to
      determine the relevance of the measurement of serum cardiac troponin I (cTnI, a
      biochemical marker with high cardiospecificity. Therefore, cTnI was compared with
      creatine kinase-MB (CK-MB) mass and to the other classical signs of myocardial
      infarction after cardiac surgery. DESIGN: A prospective study. SETTING: A
      university hospital. PARTICIPANTS: Forty-one patients undergoing coronary artery
      bypass grafting (CABG) (n = 17) or valvular replacement (n = 24). These patients
      were separated into three groups according to postoperative complications: group
      1, Q-wave PMI (n = 5); group 2, nonspecific changes (non-Q wave) on the
      electrocardiogram (ECG) and/or need of inotropic support (n = 12); group 3, no
      postoperative complication (n = 24). INTERVENTIONS: Postoperative follow-up
      consisted of serial determination of different biochemical markers (CK, CK-MB,
      cTnI), ECGs, and echocardiography. Blood samples were drawn before (H0) and 3
      (H3), 12 (H12), 20 (H20), 24 (H24), and 48 (H48) hours after the onset of
      cardiopulmonary bypass (CPB). MEASUREMENTS AND MAIN RESULTS: In all patients in
      group 3, CK-MB and cTnI concentrations increased, and peaked at H12 after CPB
      (13.4 +/- 7.7 and 7.1 +/- 4.1 micrograms/L for CK-MB and cTnI, respectively). In
      group 1, cTnI concentrations were significantly higher than in group 3 from H12
      until H48 (p < 0.002), peaked later (H24; 59.0 +/- 38.8 micrograms/L), and
      remained in plateau. In group 2, cTnI peak concentrations were significantly
      different than in groups 1 and 3 (26.2 +/- 14.8 micrograms/L) and occurred at H24
      (as in patients with Q-wave PMI). CONCLUSION: A cTnI concentration less than 15
      micrograms/L (mean + 2 standard deviations [SDs] of peak cTnI in group 3) within
      24 to 48 hours after cardiac surgery is highly suggestive of the absence of
      perioperative myocardial necrosis. Because of its higher cardiospecificity than
      CK-MB mass, and its prolonged release after myocardial necrosis, cTnI might be a
      useful tool in the diagnosis of PMI after cardiac surgery.

PMID- 9636911
TI  - Low-dose heparin appears safe and can eliminate protamine use for carotid
      endarterectomy.
AB  - OBJECTIVE: To determine the morbidity associated with carotid endarterectomy
      (CEA) when low doses of heparin (30 U/kg) are used for anticoagulation. This
      technique eliminates the need for protamine and its potentially deleterious
      effects on some patients. DESIGN: A retrospective chart review. SETTING: A large
      academic medical center. PARTICIPANTS: The records of 420 consecutive CEAs in 337
      patients (83 bilateral procedures). INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: The amount of heparin used was less than that used in most reported
      studies. Eighty-two percent of patients received only 2,000 U of heparin for
      their entire operation (range, 500 to 3,000 U). Complication rates were low.
      Neurologic complications included a 0.95% incidence of nonfatal stroke and a 2.1%
      incidence of transient neurologic deficits that resolved in the first day. There
      was no mortality. The wounds were described in the postoperative period as dry
      (96%), swollen (3%), or bloody (1%). No patients received protamine. CONCLUSION:
      The use of 5 to 10,000 U of heparin will provide anticoagulation for more than an
      hour. In CEA surgery, anticoagulation for this duration is often unnecessary. A
      smaller dose of heparin (30 U/kg) can provide adequate anticoagulation for this
      procedure while eliminating the potentially deleterious effects of protamine use.
      No additional morbidity was attributed to this technique.

PMID- 9636912
TI  - Heparin-coated bypass circuits (Carmeda) suppress the release of tissue
      plasminogen activator during normothermic coronary artery bypass graft surgery.
AB  - OBJECTIVES: To study fibrinolysis in a homogeneous first-time coronary artery
      bypass surgery (CABG) population in whom heparin-coated circuits were used.
      DESIGN: A prospective, blinded, randomized, placebo-controlled study. SETTING: A
      university hospital, tertiary care, intraoperative and postoperative intensive
      care unit. PARTICIPANTS: Twenty-one adult elective primary CABG patients.
      INTERVENTIONS: Randomized circuit-type centrifugal pump, membrane oxygenator,
      rigid cardiotomy reservoir, either placebo (n = 10) or heparin-coated (n = 11)
      (Carmeda; Medtronic Inc., Anaheim, CA). MEASUREMENTS AND MAIN RESULTS: Blood
      samples were analyzed for tissue plasminogen activator (TPA) activity, TPA
      antigen, plasminogen activator inhibitor-1 (PAI-1) activity, prothrombin complex
      F1.2, and antithrombin III (AT-III) at the following times: before
      cardiopulmonary bypass (CPB), during CPB (30 and 60 minutes), post-CPB, and day 1
      postsurgery. TPA activity and antigen increased fivefold in the placebo group
      during CPB, whereas it did not even double in the heparin-coated group. PAI-1,
      F1.2, and AT-III were not different between groups. CONCLUSIONS: Heparin-coated
      CPB circuits reduced TPA release in this homogeneous CABG population with routine
      heparin/protamine management.

PMID- 9636913
TI  - Thromboelastography with heparinase in orthotopic liver transplantation.
AB  - OBJECTIVE: To investigate the role of heparin in the postreperfusion coagulopathy
      during liver transplantation with heparinase-guided thromboelastography. DESIGN:
      A prospective, interventional study. SETTING: A university-affiliated hospital.
      PARTICIPANTS: Twenty-six patients undergoing orthotopic liver transplantation
      (OLT). INTERVENTIONS: Blood drawn at five intervals for thromboelastography
      assessment with native (12 patients) or celite blood (14 patients) compared with
      simultaneous thromboelastography traces with added heparinase. MAIN RESULTS: In
      the native samples, the prolonged R (reaction) and K (coagulation) time and
      decreased alpha angle were corrected in heparinase thromboelastograph traces
      immediately before reperfusion and 10 minutes postreperfusion. In the celite
      accelerated samples, the heparinase traces showed correction of the R and K times
      and alpha angle only at the 10-minute postreperfusion stage. In seven patients
      who had thromboelastography performed after protamine administration, there were
      no differences between celite and heparinase-celite traces. CONCLUSIONS:
      Heparinase-treated thromboelastography offered compelling evidence for the
      presence of heparin-like activity after liver graft reperfusion. The objective
      evidence provided by this modification of thromboelastography-guided protamine
      administration and was useful in identifying one of the many potential causes of
      postreperfusion bleeding in patients undergoing OLT.

PMID- 9636914
TI  - The importance of sampling site in the measurement of whole-blood platelet flow
      cytometry.
AB  - PURPOSE: Flow cytometry is an emerging technology that may be of use in
      clarifying the defects of platelet function after cardiopulmonary bypass.
      However, the technique used for platelet sampling may affect results. The
      objective of this study was to evaluate the influence of the sampling site on the
      degree of expression of a variety of platelet-associated proteins. METHODS: Whole
      blood flow cytometric assays for the detection of platelet glycoprotein (GP) Ib,
      guanosine monophosphate (GMP)-140, thrombospondin, activated GPIIb/IIIa, and
      platelet-associated factor (FXIIIa) were developed. These markers were then
      measured in samples taken simultaneously from a peripheral vein, radial artery,
      and the side port of the central venous catheter, in eight patients about to
      undergo surgery. RESULTS: When multiple samples from individual patients were
      assessed, the degree of activation with all of the activation assays (GMP-140,
      thrombospondin, activated GPIIb/IIIa, FXIIIa) was significantly greater in
      samples taken from the arterial catheter (p < 0.05) compared with the central
      venous catheter or the peripheral vein. The mean difference between sample sites
      was calculated in the study patients. Percent activation of FXIIIa from arterial
      blood was significantly greater than from the central vein and the peripheral
      vein (arterial-peripheral venous, 18.7 +/- 8.6; central venous-peripheral venous,
      3.7 +/- 3.6; p = 0.005). There was no site-related difference in detected
      expression of platelet GPIb. CONCLUSION: The site of platelet sampling
      significantly affects the degree of activation detected by flow cytometry. To
      approximate results that would be obtained from peripheral blood, samples should
      be taken from the side port of the central venous catheter and not from the
      arterial catheter in patients studied during surgery.

PMID- 9636915
TI  - Splenic laceration associated with transesophageal echocardiography.

PMID- 9636916
TI  - Esmolol resistance during anesthesia for thoracoscopically assisted coronary
      artery bypass grafting.
AB  - The anesthetic technique for two patients who underwent thoracoscopic harvesting
      of the LIMA followed by a mini-thoracotomy for surgical myocardial
      revascularization of isolated LAD artery stenosis is reported. Both patients
      unexpectedly showed esmolol resistance during anastomosis of the LIMA to the LAD
      artery. However, excellent graft patency, early extubation, and rapid recoveries
      were achieved.

PMID- 9636917
TI  - Persistent intraoperative hypotension as a presentation of bilateral subclavian
      artery stenosis.

PMID- 9636918
TI  - Preoperative valvuloplasty in a thermally injured patient with critical aortic
      stenosis.

PMID- 9636919
TI  - Refractory vasodilation after cardiopulmonary bypass for heart transplantation in
      recipients on combined amiodarone and angiotensin-converting enzyme inhibitor
      therapy: a role for vasopressin administration.

PMID- 9636920
TI  - Quantifying risk and assessing outcome in cardiac surgery.
AB  - Quality improvement, research, and reporting of outcome results can be stratified
      by preoperative risk by using a logistic regression equation or scores to correct
      for multiple risk factors. The more than 30-fold mortality differences between
      lowest and highest risk patients make it critical to stratify outcome results by
      patient severity. Probabilities are not predictions, however, and caution must be
      exercised when applying scores to individuals. Outcome assessment will grow in
      its importance to professionals, initially in the guise of quality reporting and
      improvement, but increasingly as a tool for risk assessment, patient counseling,
      and directing therapeutic decisions based on more complete information about
      patient subgroups. Physicians may be called on for recommendations in choosing
      systems for their hospitals and communities. Therefore, it is important to have
      an understanding of how such systems are developed, what factors indicate
      adequate performance of a system, and how such systems of risk stratification
      should be applied in practice.

PMID- 9636921
TI  - Monitoring of brain function during carotid endarterectomy: an analysis of
      contemporary methods.

PMID- 9636922
TI  - Computer technology for the anesthesiologist: cardiothoracic and vascular
      anesthesia on the Internet.

PMID- 9636923
TI  - CASE 3--1998. Pulmonary reperfusion edema associated with pulmonary
      thromboendarterectomy.

PMID- 9636924
TI  - Pro: during cardiopulmonary bypass for elective coronary artery bypass grafting,
      perfusion pressure should routinely be greater than 70 mmHg.

PMID- 9636925
TI  - Con: during cardiopulmonary bypass for elective coronary artery bypass grafting,
      perfusion pressure should not routinely be greater than 70 mmHg.

PMID- 9636926
TI  - Evaluation of a hemodynamic tracing.

PMID- 9636927
TI  - Off-axis view using a multiplane transesophageal echocardiography probe
      facilitates cannulation of the coronary sinus.

PMID- 9636928
TI  - Comparison of pulsatile versus nonpulsatile perfusion on the postcardiopulmonary
      bypass aortic-radial artery pressure gradient.

PMID- 9636930
TI  - Hepatitis A in waste water treatment plant workers: is vaccination necessary?

PMID- 9636929
TI  - Occupational and environmental medicine in the family medicine curriculum.

PMID- 9636931
TI  - Can corrective lenses effectively improve a color vision deficiency when normal
      color vision is required?

PMID- 9636932
TI  - Symptoms in 18,495 Persian Gulf War veterans. Latency of onset and lack of
      association with self-reported exposures.
AB  - Toxic or environmental exposures have been suggested as a possible cause of
      symptoms reported by Gulf War veterans. To further explore this hypothesis, we
      analyzed findings in 18,495 military personnel evaluated in the Department of
      Defense Comprehensive Clinical Evaluation Program. The program was established in
      1994 to evaluate Persian Gulf veterans eligible for Department of Defense medical
      care who had health concerns after service in the Persian Gulf during Operation
      Desert Shield/Desert Storm. The evaluation included a structured clinical
      assessment, a physician-administered symptom checklist, and a patient
      questionnaire addressing self-reported exposures, combat experiences, and work
      loss. Among 18,495 patients examined, the most common symptoms were joint pain,
      fatigue, headache, memory or concentration difficulties, sleep disturbances, and
      rash. Symptom onset was often delayed, with two-thirds of symptoms not developing
      until after individuals returned from the Gulf War and 40% of symptoms having a
      latency period exceeding one year. There was no association between individual
      symptoms and patient demographics, specific self-reported exposures, or types of
      combat experience. Increased symptom counts were associated with work loss, the
      number of self-reported exposures, the number of types of combat experience, and
      certain ICD-9 diagnostic categories, particularly psychological disorders.
      Prolonged latency of symptom onset and the lack of association with any self
      reported exposures makes illness related to toxic exposure less likely.

PMID- 9636933
TI  - Low response in white blood cell DNA adducts among workers in a highly polluted
      cokery environment.
AB  - Coke oven workers are often heavily exposed to polynuclear aromatic hydrocarbons
      (PAHs); this exposure has been associated with higher cancer rates among these
      workers. We assessed the exposure of cokery workers in an oil shale processing
      plant. Personal hygienic monitoring, measurement of urinary 1-hydroxypyrene (1
      OHP), and analysis of PAH-DNA adducts in white blood cells (WBCs) were performed.
      The 32P-postlabeling method was used for adduct measurement. The mean adduct
      value, 1.6 adducts per 10(8) nucleotides, did not differ significantly from the
      control value (P = 0.098). Smokers had significantly higher adduct levels than
      non-smoking workers (P = 0.002). 1-OHP levels measured in post-shift samples
      correlated with DNA adducts found in white blood cells (WBCs). We conclude that
      hygienic monitoring and measurement of urinary metabolites are essential
      background exposure data when the biologically effective dose of chemical
      carcinogens is assessed.

PMID- 9636934
TI  - Differences between descriptive and multivariate estimates of the impact of
      Chevron Corporation's Health Quest Program on medical expenditures.
AB  - This investigation focused on alternative methods for evaluating the impact of
      Chevron Corporation's Health Quest Fitness Center program on medical
      expenditures, comparing descriptive and multivariate research designs. Many
      uncontrolled studies of corporate health management programs base estimates of
      program effectiveness on descriptive analyses such as Student's tests. Unlike
      more sophisticated multivariate analyses, descriptive analyses often produce
      biased estimates of program cost savings. To test alternative research design
      methods, the investigators compared inpatient and pharmacy expenditures for
      program participants and non-participants over a 2.5-year period, using
      descriptive and multivariate regression analyses. Results showed that compared
      with non-participants, expenditures for participants were significantly lower for
      subjects who used a Health Quest fitness center at least twice weekly. Previous
      descriptive studies suggested a much broader impact. The results underscore the
      need to use multivariate analyses when evaluating the financial impact of
      corporate health management programs, especially when randomization cannot be
      used to assign participation status.

PMID- 9636936
TI  - Prevalence and incidence of stenosing flexor tenosynovitis (trigger finger) in a
      meat-packing plant.
AB  - The purpose of this study was to determine the prevalence and incidence of
      trigger finger (TF) in a meat-packing plant and explore the relationship between
      hand-tool use and the development of TF. A cross-sectional study was competed
      wherein 665 workers were interviewed and examined to determine the point
      prevalence. Subsequently, 454 TF-negative workers were followed up and examined
      twice at a median interval of 225 days. The point prevalence of TF was 14%. The
      person-year incidence rate was 12.4% and 2.6% for tool use and non-tool use
      workers, respectively. Forty-three cases of TF (75.2%) in the incidence arm of
      the study used a hand tool, for a relative risk of 4.7 (P < 0.002; 95% confidence
      interval, 1.5-23.9). Although a significant relationship was found between
      ethnicity and the presence of TF in the prevalence data, this was not confirmed
      in the incidence study. There is an increased prevalence of TF in this meat
      packing plant and high worker turnover may underestimate the true prevalence
      rates. Hand-tool use increases the risk of developing TF.

PMID- 9636935
TI  - Occupational upper extremity disorders in the federal workforce. Prevalence,
      health care expenditures, and patterns of work disability.
AB  - Upper extremity disorders (UEDs) account for a significant number of work-related
      illnesses in the US workforce. Little information exists on the distribution of
      UEDs, their associated health care and indemnity costs, or patterns of work
      disability. The study presented is an analysis of upper extremity claims within
      the federal workforce. In this study, the universe consisted of all claims
      accepted by the US Department of Labor, Office of Workers' Compensation Programs
      (OWCP), from October 1, 1993, through September 30, 1994. A total of 185,927
      claims of notices of injury were processed during the study period, and of these,
      8,147 or 4.4% had an UED diagnosis coded according to the International
      Classification of Diseases, Clinical Modification (ICD-9-CM). 5,844 claims
      involved a single UED diagnosis and were the only claims field by these employees
      between October 1, 1990, and September 30, 1994. These single claims with single
      diagnoses comprised the sample for further analysis. Mononeuritis and
      enthesopathies of the upper limb were the most common diagnoses, accounting for
      43% and 31% of the claims, respectively. Women had a higher proportion of carpal
      tunnel syndrome, "unspecified" mononeuritis, and "unspecified" enthesopathies.
      The majority of claimants for both the mononeuritis- and enthesopathy-related
      diagnoses were between 31 and 50 years of age, received only health care
      benefits, and did not incur wage loss. Health care costs for mononeuritis and
      enthesopathy claims were $12,228,755 (M = $2,849). Carpal tunnel syndrome (CTS)
      and enthesopathy of the elbow were the most costly diagnoses, accounting for 57%
      and 16% of the total, respectively. Surgical services represented the highest
      expenditures in CTS claims. Physical therapy accounted for the majority of health
      care costs for enthesopathy cases. The mean number of workdays lost for CTS and
      enthesopathy claims were 84 and 79, and the average indemnity costs were $4,941
      and $4,477, respectively. These findings indicate that while UEDs represent a
      relatively small percentage of all workers' compensation cases, the health care
      and indemnity costs are considerable. Also mean duration and pattern of work
      disability revealed that these disorders can result in chronic work disability
      similar to that observed in low back pain. The results highlight the need to
      determine whether interventions that account for the majority of costs
      significantly impact long-term outcomes. There is also a need to identify risk
      factors for prolonged disability in those who experience problems with delayed
      recovery.

PMID- 9636937
TI  - Non-fatal workplace violence workers' compensation claims (1993-1996).
AB  - More is known about fatal workplace violence than non-fatal workplace violence
      (NFWV). This study provides descriptive information on the number and cost of
      NFWV claims filed with a large workers' compensation carrier. NFWV claims from 51
      US jurisdictions were selected either by cause codes or by word search from the
      accident-description narrative. Claims reported in 1993 through 1996 were
      analyzed to report the frequency, cost, gender, age, industry, and nature of
      injury. An analysis of a random sample of 600 claims provided information on
      perpetrator type, cause of events, and injury mechanism. A total of 28,692 NFWV
      claims were filed during the study period. No cost was incurred for 32.5% of the
      claims, and 15.5% received payments for lost work. As a percentage of all claims
      filed by industry, schools had the highest percentage (11.4%) of NFWV claims, and
      banking had the highest percentage (11.5%) of cost. The majority of claims in the
      banking random sample group (93%) were due to stress. In the random sample, 90.3%
      of claims were caused by criminals (51.8%) or by patients, clients, or customers
      (38.5%). Only 9.7% were caused by an employee (9.2%) or a personal acquaintance
      of the employee (0.5%). Employers should acknowledge that NFWV incidents occur,
      recognize that the majority of perpetrators are criminals or clients rather than
      employees, and develop appropriate prevention and intervention programs.

PMID- 9636938
TI  - Comparison of workers' compensation costs for two cohorts of injured workers
      before and after the introduction of managed care.
AB  - A comprehensive safety and managed care initiative was instituted in 1991 at a
      large self-insured medical center in an effort to reduce workers' compensation
      costs. It features an on-site case management team, a preferred provider
      organization, and safety engineering efforts and ergonomic controls used
      proactively to aggressively identify and abate workplace hazards. Two worker
      populations were followed up longitudinally for three years before and after the
      initiative. Costs incurred by each cohort were compared. A 50% reduction in total
      expenditures was seen in the managed care cohort. The hospital component of the
      system saw a decrease in compensation of 62% for temporary total disability and
      38% for permanent partial disability. Medical expenditures decreased 50%.
      Dramatic reductions in costs are achievable, without compromising quality of
      care, when managed care principles and safety efforts are emphasized.

PMID- 9636939
TI  - Risk of job-related injury among construction laborers with a diagnosis of
      substance abuse.
AB  - This study attempts to determine whether a diagnosis of substance abuse among
      construction laborers is associated with an increased risk of work-related
      injuries. Records for construction laborers in Washington State who were covered
      by health insurance through the local union were matched against workers'
      compensation records in the Washington State Department of Labor and Industries.
      Using the health insurance records, we identified those who had a diagnosis of
      substance abuse during the two-year period 1990-1991. Using the workers'
      compensation records, we were then able to compare injury rates for those with
      substance abuse diagnoses with the rates for those without such diagnoses. The
      total cohort consisted of 7,895 laborers. Among the 422 who had a substance abuse
      diagnosis, the rate of time-loss injuries per 100 full-time equivalent workers
      was 15.1, compared with 10.9 among the remainder of the cohort. Most of the
      difference appeared in the 25-34-year age group, in which the rate of injury per
      100 full-time equivalent workers was 23.6 for substance abusers, compared with a
      rate of 12.2 for non-substance abusers, for a statistically significant relative
      risk of 1.93. The study suggests that younger workers might be an appropriate
      target for interventions aimed at reducing the level of substance abuse as a way
      of preventing injuries on the job. Studies by others have indicated some degree
      of success in this direction through the use of employee assistance programs in
      which the worker is referred to specific programs or providers for treatment. The
      state legislature in Washington has recently passed legislation providing
      incentives for the use of employee assistance programs. More effort is needed,
      however, to evaluate the effectiveness of such programs.

PMID- 9636940
TI  - Schizophrenia-specific basic symptoms. A successful replication.
AB  - Several investigations showed that the Frankfurt Complaint Questionnaire (FCQ)
      has no diagnostic specificity. However, in a preceding study two new FCQ
      subscales were developed: FCQ-S, sensitive to schizophrenia, and FCQ-A, sensitive
      to alcoholism. The aim of the present study was to replicate the diagnostic
      sensitivity of those subscales. Four groups were considered: schizophrenics with
      marked negative symptoms (n = 25); schizophrenics with no or mild negative
      symptoms (n = 25); alcoholics (n = 25); patients with obsessive-compulsive
      disorder (n = 15). FCQ original subscales and total score did not differ between
      groups. As expected, in FCQ-S both schizophrenic groups had significantly higher
      scores than the other groups; FCQ-A failed to show group differences but was
      significantly related to alcoholism markers.

PMID- 9636941
TI  - Symptom structure in schizophrenia: two-, three- or four-factor models?
AB  - Beside the syndromic dichotomy (negative-positive), other symptomatic dimensions
      have been described in schizophrenia. A question of interest is, therefore, to
      know which symptom structures can be individualized to characterize
      schizophrenia. Using confirmatory factor analysis in 135 patients, a two-factor
      model (negative-positive), a three-factor model (negative-positive
      disorganization) and a four-factor model (negative-positive-disorganization
      relational) were primarily identified with SANS (Scale for the Assessment of
      Negative Symptoms) and SAPS (Scale for the Assessment of Positive Symptoms). In
      contrast, no models could be identified with PANSS (Positive and Negative
      Syndrome Scale). The results confirm the relevance of other syndrome dimensions,
      beside the negative and positive ones and suggest that SANS-SAPS was more useful
      than PANSS in identifying an adequate dimensional factor structure of
      schizophrenic symptoms.

PMID- 9636942
TI  - Disturbance of consciousness due to methamphetamine abuse. A study of 2 patients.
AB  - The present paper reports 2 cases of methamphetamine abuse. Following consecutive
      methamphetamine administration, the patients developed acute intoxication, during
      which time they showed a unique type of disturbance of consciousness: delirium
      and twilight state. In both cases, mental status changed, passing through three
      distinct stages: restlessness and insomnia, hallucinatory paranoid state, and
      disturbance of consciousness. A review of the literature suggests that
      disturbance of consciousness may occur occasionally during the course of
      amphetamine and methamphetamine intoxication, although these symptoms can be
      overlooked easily due to confounding symptomatology.

PMID- 9636943
TI  - Psychopathological assessment and diagnosis. A study of specificity of single
      symptoms.
AB  - The importance of single symptoms in the diagnostic process has not been
      adequately studied, mainly because of the complexity of the information involved.
      The aim of the present study is to investigate the interconnection between
      psychopathological assessment and diagnostic classification, with the aid of a
      nonparametric, inductive pattern recognition method. Using the concept of
      inductive logic and a theory of inductive knowledge acquisition, a model has been
      developed to describe psychopathological assessment and diagnostic
      classification. Based on a comprehensive psychopathological assessment in 837
      patients with 14 different diagnoses, classification values were calculated for
      specific symptoms in different diagnostic groups. Furthermore, nonparametric
      statistical procedures have advantages over discriminant analytic approaches:
      more information is utilized in differentiating the groups and differentiations
      can be made between more groups, whereby the rate of correctly classified cases
      is comparable with discriminant analytic approaches. The pattern recognition
      method appears to illustrate the multidimensional, medical decision-making in a
      comprehensible way.

PMID- 9636944
TI  - Adolescent ballet school students: their quest for body weight change.
AB  - Body mass index (BMI) and body type of female and male adolescent ballet dancers
      (n = 90) and school students (n = 156) were determined. Participants were asked
      for the body weight she or he would prefer, and ballet students were administered
      the Eating Attitudes Test-40 (EAT-40). Results between age groups and with
      reference values were compared. Both in dancers and controls, girls wanted to
      lose more body weight than boys, with female ballet dancers more than female
      controls. The desire for reducing body weight was expressed by female ballet
      dancers of all BMI percentiles and body types, with the highest difference
      between real and desired body weight in 11-, 13-, and 16-year-olds. In the other
      groups, a quest for lower body weight was expressed only by adolescents of higher
      BMI and pyknomorphic and/or mesomorphic body type. Female ballet dancers of all
      age groups sought to reach body weights below the 5th percentile or below 82% of
      normal body weight. Desired body weight change was influenced by BMI and body
      type and correlated positively with EAT-40 score.

PMID- 9636945
TI  - On the validity of the Beck Depression Inventory. A review.
AB  - The present review discusses validity aspects of the Beck Depression Inventory
      (BDI) on the basis of meta-analyses of studies on the psychometric properties.
      Shortcomings of the BDI are its high item difficulty, lack of representative
      norms, and thus doubtful objectivity of interpretation, controversial factorial
      validity, instability of scores over short time intervals (over the course of 1
      day), and poor discriminant validity against anxiety. Advantages of the inventory
      are its high internal consistency, high content validity, validity in
      differentiating between depressed and nondepressed subjects, sensitivity to
      change, and international propagation. The present paper outlines agreements and
      contradictions between the various studies on the BDI and discusses the potential
      factors (composition of the subject sample, statistical procedures, point in time
      of measurement) accounting for the variance in their results. The Beck Depression
      Inventory (BDI) is world-wide among the most used self-rating scales for
      measuring depression. Since the test construction in 1961, the test has been
      employed in numerous (more than 2,000) empirical studies. The present review will
      only consider those investigations which are primarily concerned with the
      validity or the psychometric properties of the BDI. Since most studies are
      oriented along the criteria of the classical test theory, our review will discuss
      to what extent the BDI meets these criteria.

PMID- 9636946
TI  - Disordered differentiation of memory T cells in rheumatoid arthritis.

PMID- 9636947
TI  - Aspiration and injection of joints.

PMID- 9636948
TI  - Joint manifestations in Behcet's disease. A review of 340 cases.
AB  - OBJECTIVES: To gain additional knowledge on the joint manifestations of Behcet's
      disease, with special attention to unusual forms. PATIENTS AND METHODS:
      Retrospective review of 340 cases with joint manifestations identified among 601
      cases of Behcet's disease seen over a 15-year period. All the patients met
      International Study Group for Behcet's disease criteria. Radiographs of all
      joints with arthritis were obtained. Starting ten years ago, a radiograph of the
      sacroiliac joint was taken routinely. RESULTS: Joint manifestations were present
      in more than half the patients (56.57%) and were inaugural in 18.23% of cases.
      The knees and ankles were the joints most commonly affected. Monoarthritis and
      oligoarthritis were seen in 16.17% and 11.76% of cases, respectively and
      polyarthritis involving the large limb joints and the small joints of the hands
      and feet in 17.05% of cases. Unusual forms included polyarthritis with
      deformities and/or destruction (n: 8, including two patients who also met
      criteria for rheumatoid arthritis), pseudogout (n: 5), popliteal cyst (n: 3,
      including one case imitating deep vein thrombosis), myositis (n: 1),
      spondylarthropathy (n: 5), and Sjogren's syndrome (n: 2). Children were more
      likely than adults to have joint manifestations (73.68%) and polyarthritis
      (35.7%). CONCLUSION: Joint manifestations are common in Behcet's disease. Their
      unusual forms deserve to be known since they can raise diagnostic problems when
      they are inaugural.

PMID- 9636949
TI  - Rheumatoid arthritis in Congo-Brazzaville. A study of thirty-six cases.
AB  - OBJECTIVES: To define the epidemiology, clinical features and outcomes of
      rheumatoid arthritis in a hospital-based population in Congo-Brazzaville.
      PATIENTS AND METHODS: We retrospectively reviewed the medical records of the 36
      subjects seen on an inpatient or outpatient basis at our rheumatology department
      who met American College of Rheumatology criteria for rheumatoid arthritis.
      RESULTS: There were 28 women and eight men (male to female ratio, 0.28), with a
      mean age of 43.5 years. The total number of patients seen at our department
      during the study period was 3518, yielding a prevalence of 1% for rheumatoid
      arthritis. Seven per cent of the patients with inflammatory joint disease had
      rheumatoid arthritis. Mean disease duration was 9.5 years (range, 1-25 years).
      The onset was gradual in every case and distal joints were affected first in 33
      patients. All the patients but one had bilateral symmetric polyarthritis;
      affected joints included the proximal interphalangeal joints (n: 33), the
      metacarpophalangeal joints (n: 27), the wrists (n: 27), the metatarsophalangeal
      joints (n: 20), the knees (n: 26), the elbows (n: 18), the hips (n: 4), the
      temporomandibular joints (n: 4), and the cervical spine (n: 5). Boutonniere
      deformity of the fingers was the most common joint deformity (n: 15), followed by
      ulnar drift (n: 9). Three patients had tenosynovitis, two had tendon rupture, one
      had carpal tunnel syndrome and one had rheumatoid nodules. Rheumatoid factors
      were found in 70% of cases. Evidence of chondrolysis was seen on roentgenograms
      in every case. Gold and chloroquine were the two most commonly used second-line
      agents. Seven patients were on prednisone, in a mean daily dose of 6 mg. Mean
      follow-up was 15 months (range: 3-36 months). Steinbrocker's disease activity
      stage was IV in 14 patients and III in eight patients; Steinbrocker's functional
      stage was IV in five patients and III in three. CONCLUSION: The features and
      outcomes of rheumatoid arthritis in Congo-Brazzaville match textbook descriptions
      except for a lower prevalence of extraarticular manifestations. Similar findings
      have been reported for East Africa, South Africa, and some countries of West
      Africa.

PMID- 9636950
TI  - Adhesive capsulitis of the shoulder: an open study of 40 cases treated by joint
      distention during arthrography followed by an intraarticular corticosteroid
      injection and immediate physical therapy.
AB  - OBJECTIVE: To evaluate the short- and long-term efficacy of joint distention
      during arthrography followed by an intraarticular corticosteroid injection then
      by high-intensity physical therapy and use of an abduction splint in an open
      study of 40 patients with adhesive capsulitis of the shoulder. METHODS: Patients
      were evaluated on D0, D5 (i.e., before discharge) and D30 for pain severity
      assessed using a four-point scale (0-3) and for passive ranges of abduction,
      internal rotation and external rotation of the shoulder. RESULTS: Mean pain
      severity improved significantly from 2.18 +/- 0.6 (mean +/- SD) on D0 to 1.74 +/-
      0.5 on D5 (P: 0.01) and 0.92 +/- 0.5 on D30 (P: 0.02). Passive range of abduction
      increased significantly from 44.8 degrees +/- 1.54 degrees on D0 to 68 degrees +/
      15 degrees on D5 (P: 0.05), whereas the difference between D5 and D30 (71
      degrees +/- 13 degrees) was not significant (P: 0.8). Similarly, passive range of
      external rotation increased significantly from 4.3 degrees +/- 0.6 degree on D0
      to 13.5 degrees +/- 0.5 degree on D5 (P = 0.04) and showed a nonsignificant
      increase from D5 to D30 (17 degrees +/- 13 degrees, P: 0.2). CONCLUSION: Joint
      distention during arthrography followed by an intraarticular corticosteroid
      injection then by high-intensity physical therapy significantly improved pain and
      passive range of motion within the first five days, and these gains were
      sustained after one month.

PMID- 9636951
TI  - Conservative inhospital management of low back pain patients. Factors predicting
      two-year outcomes.
AB  - OBJECTIVE: To evaluate the course of symptoms and occupational outcomes in low
      back pain patients two years after conservative inhospital therapy. METHODS:
      Retrospective medical chart study of all patients admitted to a rheumatology
      department in Geneva in 1993, and telephone interview two years after the
      admission. RESULTS: Eighty of the 99 patients (81%) identified by the chart
      review were interviewed by telephone. The course of symptoms (evaluated based on
      subjective assessments and on the number of subsequent admissions) was similar in
      the patients who had acute (n = 33) and chronic (n = 47) low back pain at the
      index admission. Patients who had not returned to work were significantly more
      likely to report persistent pain (P < 0.001). As many as 61% of patients had not
      resumed work. Sick leave duration and symptom duration at admission were the
      factors that had the largest effects on prognosis. Over 90% of patients who were
      put on sick leave for more than four weeks did not return to work. Permanent
      cessation of work was recorded in 82% of manual laborers versus 27% of patients
      in sedentary jobs (P < 0.001). CONCLUSION: Our results are ascribable, at least
      in part, to the fact that our population included large numbers of patients with
      persistent pain and of blue collar workers with physically-challenging jobs. Sick
      leave duration and occupation were the best predictors of the course of symptoms
      and work status.

PMID- 9636952
TI  - Lean tissue mass is a better predictor of bone mineral content and density than
      body weight in prepubertal girls.
AB  - PURPOSE AND METHODS: Body weight is the most extensively studied correlate of
      bone mass and is widely used as a covariate in statistical evaluations of bone
      mineral parameters. Lean tissue mass (LTM) also correlates with bone mass. We
      evaluated the correlations linking each of these two parameters with bone mineral
      content and bone mineral density in 41 prepubertal girls, including ten swimmers,
      18 gymnasts and 13 nonathletes. Lean tissue mass, bone mineral content and bone
      mineral density were measured using dual-energy X-ray absorptiometry (Hologic QDR
      1000/W; Hologic Inc., Waltham, MA, USA). Forward stepwise multiple regression was
      used to evaluate correlations linking bone mineral content or density (the
      dependent variables) to body weight or lean tissue mass (the independent
      variables). RESULTS: Body weight and lean tissue mass showed strong correlations
      with all bone mineral content and density measurements in the simple linear
      regression analysis, with lean tissue mass yielding the highest Pearson's
      correlation coefficients. In the multiple regression model, lean tissue mass
      consistently explained the largest proportion of the variance, whereas body
      weight had little influence or was eliminated from the model. The slopes of the
      regression lines of bone mineral content or density on body weight were
      significantly steeper in the subgroup of gymnasts (P < 0.001), whereas the slopes
      of the regression lines of bone mineral content or density on lean tissue mass
      were significantly less steep in the swimmers (P < 0.05). CONCLUSION: Our data
      indicate that lean tissue mass is a significant predictor of bone mass in
      prepubertal girls and explains a larger part of the variance of bone mineral
      content and density than body weight. Use of body weight as a covariate in
      studies of bone mineral density may lead to erroneous results in prepubertal
      girls.

PMID- 9636953
TI  - Update on lumbar spinal stenosis. Retrospective study of 62 patients and review
      of the literature.
AB  - PURPOSE AND METHODS: Although lumbar spinal stenosis syndrome is extremely
      common, considerable controversy continues to surround its classification,
      diagnosis, and treatment. We retrospectively reviewed the medical charts of 62
      patients admitted for lumbar spinal stenosis syndrome, and we compared our
      findings to those in the literature. There were 31 women and 31 men. Mean age was
      71.8 years. The most common symptoms were positional radiculopathy (92%) and low
      back pain (95%). The more suggestive sign of pseudoclaudication was observed in
      only 75% of cases, in keeping with earlier studies. Neurologic symptoms
      consisting primarily in mild motor loss were present in 15 patients. RESULTS: The
      most common physical finding was pain during spinal extension (70%). Adopting a
      bent forward position during walking, a very suggestive manifestation, was seen
      in 15 patients. Imaging study findings included extensive changes in the discs
      and facet joints, disc protrusion, scoliosis, and degenerative spondylolisthesis.
      Myelography was rarely needed. There are no criteria sets for lumbar spinal
      stenosis syndrome. The diagnosis rests on clinical grounds, and extensive imaging
      studies are usually unnecessary. Our patients were treated with repeated
      corticosteroid injections into the thecal sac or epidural space and/or into the
      facet joints. Only eight patients required surgery. CONCLUSION: Our study
      supports the view that most cases of lumbar spinal stenosis can be managed
      conservatively.

PMID- 9636954
TI  - Dysphagia, headache, and dizziness as symptoms of cervical spine disorders.

PMID- 9636955
TI  - Abducens palsy after an intrathecal glucocorticoid injection. Evidence for a role
      of intracranial hypotension.
AB  - We report a case of abducens palsy eight days after an intrathecal glucocorticoid
      injection followed by post-lumbar puncture syndrome. T1-weighted magnetic
      resonance imaging scans showed marked diffuse postgadolinium enhancement of the
      supra- and infratentorial meninges consistent with intracranial hypotension
      syndrome. The palsy resolved almost completely and a repeat magnetic resonance
      imaging scan done after four months was normal. The mechanism of the meningeal
      thickening and contrast enhancement is discussed.

PMID- 9636956
TI  - Optic neuropathy in a child with primary Sjogren's syndrome.
AB  - An eight-year-old girl developed optic neuritis followed by primary Sjogren's
      syndrome confirmed by a lip biopsy. Glucocorticoid therapy combined during six
      months with monthly intravenous pulse cyclophosphamide ensured resolution of the
      sicca syndrome but failed to improve the visual impairment. This is the second
      pediatric case of optic neuritis associated with primary Sjogren's syndrome, and
      the first pediatric case in which optic neuritis was the only neurologic
      manifestation.

PMID- 9636957
TI  - Brachial plexopathy and Horner's syndrome as the first manifestations of internal
      jugular vein thrombosis inaugurating polycythemia vera.

PMID- 9636958
TI  - Amyloidosis of the urinary bladder: a rare cause of total hematuria in rheumatoid
      arthritis.

PMID- 9636959
TI  - Spondylarthropathy in patients with the HIV.

PMID- 9636960
TI  - Osteosarcoma of the sacrum complicating Paget's disease of bone.

PMID- 9636961
TI  - Myocardial perfusion after coronary artery bypass surgery. A study using
      ectomographic myocardial scintigraphy and adenosine provocation.
AB  - A study was conducted to determine the time dependency of myocardial perfusion
      improvement after coronary artery bypass graft (CABG) surgery. Seventeen 3-vessel
      diseased patients (16 male, 1 female) scheduled for CABG surgery from a cardiac
      surgical and intensive-care unit were examined. Ten of the 17 patients returned
      for examination after 1 year. A titrated adenosine infusion was used to expose
      reversible ischemia. Tc99m-sestamibi was injected at rest and at maximum
      adenosine infusion rate, and isotope distribution was determined using
      ectomographic myocardial scintigraphy. Visually scored percent isotope uptake
      defect size and percent uptake reduction were assessed. It was found that resting
      isotope uptake defects were unchanged 1 h after surgery, increased in severity
      after 1 week, and after 1 year were 24% less than the preoperative scores (p <
      0.01) and 55% less than after 1 week (p < 0.001). It was found that adenosine
      infusion induced a 57% increase in average defect score preoperatively (p <
      0.001) but no increase postoperatively. No differences were seen between regions
      supplied by arterial or venous grafts. Isotope uptake defects increased between 1
      h and 1 week after CABG surgery, and after 1 year the scores were less than those
      recorded preoperatively and after 1 week. Adenosine-induced reversible isotope
      uptake changes seen preoperatively were eliminated postoperatively in all vessel
      regions.

PMID- 9636962
TI  - Autologous blood patch pleurodesis in spontaneous pneumothorax with persistent
      air leak.
AB  - In a prospective study series of 167 patients with tube thoracostomy for
      spontaneous pneumothorax in 1993-1996, 32 patients (age range 16-79 years, mean
      age 45.5 years) were treated with autologous blood-patch pleurodesis for
      persistent air leak. In 27 (84%) of cases the air leak ceased within 72 h after
      the pleurodesis. The duration of air leak was significantly shorter (p < 0.01)
      than in simple drainage. Empyema developed in three cases, and two patients with
      failed pleurodesis required open thoracotomy. Minor complications, mainly fever
      and pleural effusion, occurred in nine patients. Neither analgesia nor sedation
      was required during or after pleurodesis. There was no recurrence of pneumothorax
      during 12-48 months of observation, whereas simple drainage was followed by
      recurrence in 22 patients. Blood-patch pleurodesis is a simple, effective and
      painless method in pneumothorax, but carries an increased risk of intrathoracic
      infection.

PMID- 9636963
TI  - The Barath Cutting Balloon versus conventional angioplasty. A randomized study
      comparing acute success rate and frequency of late restenosis.
AB  - In a randomized multicenter study initial success rate and 6 months' follow-up
      were compared between coronary angioplasty performed with the Barath Cutting
      Balloon (group A, n = 32) and conventional balloons (group B, n = 32) in patients
      with type A or B lesions in native coronary arteries. The culprit lesion was not
      reached in one patient in group A. Initial success rates were similar with and
      without additional stenting (8 in group A and 10 in group B). Angiographic follow
      up data (in 95%) revealed a non-significant improvement in minimal lumen
      diameter, diameter stenosis in group A. Restenosis developed in 16.7% of group A
      vs 25.8% of group B, (p = 0.57). A separate analysis of stented patients showed
      no restenosis in group A and restenosis in 4 out of 10 patients in group B (p =
      0.10). A possible beneficial effect of the Cutting Balloon with respect to in
      stent restenosis requires further studies.

PMID- 9636964
TI  - Activated and total coagulation factor VII, and fibrinogen in coronary artery
      disease.
AB  - Fibrinogen (FBG) and total coagulation factor VII (FVIIc) concentrations are
      higher in those patients with coronary artery disease who are at increased future
      risk of acute ischemic events. The relationship between activated factor VII
      (FVIIa) and cardiovascular events, however, has not been intensively studied.
      Data were collected from 401 consecutive patients who underwent coronary
      angiography because of suspected coronary artery disease. Conventional risk
      factors FVIIc, FVIIa and FBG were assessed in relation to the severity of
      coronary artery disease, left ventricular ejection fraction, and previous
      clinical events. A strong positive correlation was found between FVIIa and FVIIc
      (p < 0.001), but neither FVIIa nor FVIIc correlated with FBG. No correlation was
      found between FVIIa, FVIIc or FBG levels and stenosis score for the severity of
      coronary artery disease, and all were similar in patients with stable or unstable
      angina pectoris. Multivariate regression analysis showed FVIIc to be higher in
      women (p = 0.004), and positively related to triglycerides (p = 0.001) and HDL
      cholesterol (p = 0.006), but not to a previous myocardial infarction or total
      cholesterol. FVIIa, on the other hand, was lower in patients with a previous
      myocardial infarction (p = 0.004), higher in women (p = 0.001) and those that
      previously had undergone percutaneous transluminal coronary angioplasty (p =
      0.039), and positively related to total cholesterol (p = 0.011), duration of
      coronary artery disease (p = 0.032), and smoking (p = 0.008). FBG was positively
      associated with a previous myocardial infarction (p = 0.013), hypertension (p =
      0.016), smoking (p = 0.005), and the thrombocyte count (p < 0.001). Finally,
      stepwise logistic regression analysis verified a previous myocardial infarction
      to be negatively associated with FVIIa (p = 0.03), and positively with FBG (p =
      0.03), total cholesterol (p = 0.02), and the severity of coronary artery disease
      (p < 0.001). In conclusion, in patients suspected of coronary artery disease
      undergoing cardiac catheterization, FVIIa was decreased and FBG increased in
      those who had a previous myocardial infarction. FVIIa, FVIIc, or FBG levels were
      not, however, related to the severity of coronary artery disease, and they were
      similar in patients with stable or unstable angina pectoris.

PMID- 9636965
TI  - Gene expression of profibrotic mediators in bronchiolitis obliterans syndrome
      after lung transplantation.
AB  - Bronchiolitis obliterans syndrome (BOS) develops in one-third of lung transplant
      recipients. A fibroproliferative process involving mesenchymal cells is observed
      histopathologically. In order further to evaluate the pathomechanisms of BOS, the
      gene expression of platelet-derived growth factor (PDGF)-B and transforming
      growth factor (TGF)-beta 1 in bronchoalveolar lavage (BAL) cells of six lung
      transplant recipients and appropriate controls was studied. Equal amounts of
      total RNA were submitted to semiquantitative reverse transcription/polymerase
      chain reaction (RT-PCR), amplifying actin, PDGF-B and TGF-beta 1 using
      established protocols and primer sets. The signal/actin ratio was calculated
      based on laser densitometry measurements. TGF-beta 1 transcripts were detected in
      all samples, and a slight increase in BOS patients was observed. PDGF-B mRNA was
      increased in BAL samples from BOS patients compared to unaffected recipients and
      controls. Plotting the FEV1 in percent of vital capacity and the PDGF expression
      in BOS patients revealed an increased PDGF signal preceding lung function
      deterioration. The data were consistent with the hypothesis based mainly on in
      vitro findings that PDGF and TGF-beta contribute to the development of BOS.

PMID- 9636966
TI  - Thymic lymphoepithelioma-like carcinoma associated with thymoma in a patient with
      ocular myasthenia.
AB  - A 65-year-old woman with ocular myasthenia was found to have three tumours in the
      anterior mediastinum, revealed by magnetic resonance imaging. All three lesions
      were radically resected. Histologically, one was a mixed-type thymoma, one a
      thymic lymphoepithelioma-like carcinoma, and the third had features of both these
      types. This appears to be the first reported case of coexisting thymic
      lymphoepithelioma-like carcinoma (TLC) and thymoma associated with ocular
      myasthenia.

PMID- 9636967
TI  - Resection of distal tracheal and carinal tumours with the aid of cardiopulmonary
      bypass.
AB  - Two cases of carinal and tracheal reconstruction with the aid of cardiopulmonary
      bypass (CPB) are presented. The technical problems of surgery and anaesthesia
      which necessitated CPB in these two patients are discussed. CPB provides both
      adequate oxygenation and an unobstructed surgical field with optimal access to
      the trachea and carina. It permits atraumatic handling of the airways and
      reduction of anastomotic tension during the repair.

PMID- 9636968
TI  - Bochdalek hernia in an adult.
AB  - Congenital diaphragmatic Bochdalek hernia is rarely seen in adults. It may
      present with jejunal perforation and strangulation. In a 28-year-old man
      presenting with nausea and vomiting, absence of respiratory murmur at
      auscultation, loops of small intestine with air-fluid levels were
      radiographically visualized in the left hemithorax. Surgery revealed 1.5-m of
      herniated jejunum with three perforations and necrotic areas, 40 cm of which was
      resected. The patient remains well ten years postoperatively.

PMID- 9636969
TI  - Assessment of left ventricular dysfunction and remodeling by determination of
      atrioventricular plane displacement and simplified echocardiography.
AB  - Heart failure is a common disease characterised by poor prognosis and frequent
      hospitalisations, constituting a major economic burden to society. Mortality and
      morbidity can be reduced by optimal treatment, requiring objective evaluation of
      cardiac function and anatomy. The development of symptomatic HF can be prevented
      by initiating adequate treatment in early stages when LVD is still asymptomatic.
      Asymptomatic patients can be identified only by screening for LVD among patients
      at risk of developing HF, such as those with IHD, HT, and diabetes. However,
      there is a severe lack of resources to assess cardiac function and anatomy in all
      patients at risk. Consequently, many patients with latent HF will remain
      undetected, and in patients with symptomatic HF treatment will not be optimal.
      Simplified echocardiography, a 5-minute echocardiogram based on visual estimation
      of cardiac function and anatomy, is an inexpensive and accurate method for
      diagnosis and screening for latent and symptomatic HF. The long axis shortening
      of the LV is related to LV function and can be measured by AVPD. Determination of
      left AVPD is a reliable, reproducible, readily mastered, quickly performed and,
      therefore, inexpensive method that can be used in almost all patients for
      evaluation of LV function, as well as for prognostication in HF. Left AVPD
      reflects both systolic and diastolic LV function. Simplified echocardiography is
      useful for screening of asymptomatic patients at risk of developing HF, and for
      routine diagnostic purposes in patients with symptoms suggestive of HF. In
      patients with LVSD, simplified echocardiography may be combined with a
      determination of left AVPD for prognostication and for optimal detection of
      changes in LV function over time.

PMID- 9636970
TI  - The role of steroids and their effects on phospholipase A2. An animal model of
      radiculopathy.
AB  - STUDY DESIGN: The possible role of phospholipase A2 in an animal model for lumbar
      radiculopathy and mechanisms of epidural steroid injections were studied.
      OBJECTIVES: To clarify the pathophysiologic mechanism of the recently proved
      animal model for lumbar radiculopathy and to characterize further the mechanisms
      of action of steroids. SUMMARY OF BACKGROUND DATA: There have been several
      reported animal models of peripheral neuropathy. Recently an animal model that
      shows reliable behavioral and neurochemical changes was proposed, and epidural
      steroid injections in this model were effective in the reduction of thermal
      hyperalgesia and allodynia. METHOD: In a behavioral study, 24 rats were divided
      into 4 groups: Group I, loose ligature of the left L4 and L5 nerve roots with 4-0
      chromic gut sutures and an epidural injection of 0.1 mL of saline at 3 days after
      surgery; Group II, same as Group I but with an epidural injection of 0.1 mL of
      betamethasone on the day before the operation; Group II, same as Group II except
      injection at 1 day after surgery; Group IV, same as Group II except injection at
      3 days after surgery. To test the phospholipase A2 activity in the nerve roots
      and dorsal root ganglia after the operation, eight rats were killed at given
      intervals. Analysis of variance techniques were used to test behavioral pattern
      changes and phospholipase A2 activity across time in each group. RESULTS: Thermal
      hyperalgesia reached its maximal point at 3 weeks after surgery in Group I, but
      in steroid injection groups, the recovery from hyperalgesia was faster than in
      Group I. However, there was no significant difference in recovery time among
      steroid injection groups. The level of phospholipase A2 activity was at its
      maximum at 1 week after surgery in Groups I and IV. It showed a steady reduction
      in the steroid group, whereas it remained relatively high and dropped rapidly
      after 3 weeks in the saline-treated group, and returned to the level of a normal
      nerve root at 6 weeks after surgery. CONCLUSION: These results suggest that the
      behavioral pattern changes observed in the irritated nerve root model are caused
      in part by a high level of phospholipase A2 activity initiated by inflammation,
      and that the mechanism of action of epidural steroid injection in this model is
      inhibition of phospholipase A2 activity.

PMID- 9636971
TI  - Is there a clinical correlate to the histologic evidence of inflammation in
      herniated lumbar disc tissue?
AB  - STUDY DESIGN: The presence of inflammatory cells was examined
      immunohistochemically in routinely processed resection specimens of the lumbar
      disc. The histologic results were compared with prospectively obtained clinical
      data. OBJECTIVES: To assess the clinical relevance of inflammatory cells in
      herniated lumbar disc specimens. SUMMARY OF BACKGROUND DATA: It is postulated
      that in addition to nerve root compression, an inflammatory stimulus of the
      herniated lumbar disc is responsible for sciatic pain and radiculopathy. However,
      the clinical relevance of the histologically described inflammatory infiltrates
      is not defined clearly. METHODS: Disc specimens from 44 patients who underwent
      surgery for lumbar disc herniation were studied immunohistologically. Before
      surgery, severity of pain was classified in each patient according to a visual
      analog scale, and general clinical data were recorded prospectively. RESULTS:
      Varying amounts of inflammatory cells could be demonstrated in the resected disc
      tissue. In the statistical analysis, no statistically significant correlation
      between the histologic evidence of macrophage infiltrates and the pain grading
      scale or the clinical data was noted. CONCLUSIONS: There is no statistically
      significant correlation between macrophage infiltrates in herniated lumbar disc
      specimens and the obtained clinical data.

PMID- 9636972
TI  - Patients with low back pain not returning to work. A 12-month follow-up study.
AB  - STUDY DESIGN: A prospective study of patients treated with a light mobilization
      program for long-term low back pain. OBJECTIVES: To examine whether medical,
      psychological, or social factors predict failure to return to work within 12
      months in the Scandinavian system of compulsory workers' compensation and social
      insurance, after a light mobilization program administered 8-12 weeks after
      initial sick leave. SUMMARY OF BACKGROUND DATA: The relative power of predicting
      factors varies in previous work, and there are no previous data on prognostic
      factors for light mobilization programs. METHOD: Patients (n = 260) on sick leave
      for 8-12 weeks for low back pain were examined with a battery of psychological
      and medical tests, before entering a light mobilization program. The treatment
      was given regardless of radiographic or clinical findings. The patients were
      encouraged to be active participants in the management and prevention of their
      back pain. Their sick leave status then was checked through registers 12 months
      after they had entered the treatment program. RESULTS: For those not returning to
      work within 12 months (23%), only combined models had acceptable predictive power
      (77%; discriminant analyses). Dominant variables were low Internal Health Locus
      of Control Score, restricted lateral mobility, and reduced work ability. The
      predictive value of each set of variables, taken alone, was significant only for
      medical variables (67% correct prediction). CONCLUSIONS: The final discriminant
      function may have potential as a brief screening instrument for the number of
      patients with low back pain who do not benefit from the light mobilization
      program.

PMID- 9636973
TI  - A human cadaver model for determination of pathologic fracture threshold
      resulting from tumorous destruction of the vertebral body.
AB  - STUDY DESIGN: Thoracic vertebrae were subjected to compressive loads after
      drilling of the centrum to simulate destruction from metastatic tumorous
      involvement. OBJECTIVE: To determine whether a threshold exists that is
      predictive of fractures to establish a correlation between significant variables
      and vertebral strength. SUMMARY OF BACKGROUND DATA: The mechanical effects of
      metastatic destruction of thoracic vertebral bodies and their correlation to
      pathologic fractures has been analyzed in few studies. In additional studies on
      intact vertebral strength, investigators have determined that bone mineral
      density and geometric factors are important. METHOD: Fifty-four cadaveric
      thoracic vertebrae were studied. All were examined by quantitative computed
      tomography. T4 and T10 served as mechanical controls to predict the intact
      strength of T7. The test vertebrae were drilled from the anterior cortex through
      to the posterior cortex before they were loaded. RESULTS: Linear correlation
      between the strength of T4 and T10 in each spine supported the predicted
      strengths of T7. Because of variation from other factors, no threshold defect
      size was noted beyond which failure consistently occurred. Results of linear
      correlation analyses showed that the best combination of parameters for
      predicting vertebral strength was the product of bone mineral density and the
      remaining intact vertebral body cross-sectional area. This vertebral strength
      index correlated linearly with the strength of intact and compromised T7
      vertebrae (r2 = 0.52). CONCLUSIONS: The vertebral strength index can be used to
      predict the strength of any thoracic vertebra. When compared with an idealized
      vertebral strength index based on the intact vertebral cross-sectional area and
      normal bone mineral density, a patient's actual vertebral strength index can be
      used as one of the criteria for prophylactic stabilization.

PMID- 9636974
TI  - Changes in cadaveric cancellous vertebral bone strength in relation to time. A
      biomechanical investigation.
AB  - STUDY DESIGN: A biomechanical study was conducted during a 3.5-day period to test
      for changes occurring in pullout strengths of cancellous screws inserted into
      human cadaveric vertebral bodies. OBJECTIVES: To quantify, within the testing
      time of 3.5 days, the possible changes to the mechanical properties of cadaveric
      vertebral bodies, resulting from structural degradation caused by postmortem,
      time-dependent, autolytic processes during mechanical testing of implant-bone
      biomechanics. SUMMARY OF BACKGROUND DATA: Biomechanical testing of whole spinal
      implants and analysis of the screw-bone interface of spinal implants is an area
      of clinical interest that frequently requires the use of cadaveric spine
      specimens. Changes in vertebral bone properties during the testing period may
      invalidate experimental results, but no data are available on degradation of bone
      during the testing period. METHODS: Anterior oblique cancellous screws were
      inserted into human vertebral bodies from which the ventral cortex had been
      removed. The pullout strength was measured at 0, 24, 60, and 84 hours after
      insertion. The tests were performed on 48 human vertebral bodies, which were
      stored by freezing to -23 C, thawed for testing, and kept at room temperature
      during the testing time for as long as 84 hours. RESULTS: The axial pullout
      strength showed no statistically significant change during 84 hours (P = 0.15).
      There were no significant differences attributable to vertebral level from T4 to
      L4, probably because the ventral cortices had been removed (P = 0.7).
      CONCLUSIONS: During 3.5 days, there were no changes in pullout strength of
      vertebral cancellous bone. In biomechanical studies during a maximum period of 3
      days with a small number of cadaveric spines (e.g., four spine specimen) the time
      dependent changes in pullout strength play a less significant role than do the
      interspine differences. Interspine differences should be regarded as an important
      factor to be considered in the design of biomechanical tests.

PMID- 9636975
TI  - Moments and forces during pedicle screw insertion. In vitro and in vivo
      measurements.
AB  - STUDY DESIGN: Moments and forces during pedicle screw insertion were measured in
      vivo and in vitro and were correlated to several parameters of the screw-bone
      interface. OBJECTIVES: To compare the in vitro and in vivo screw insertion loads
      and to relate these measurements to bone mineral density, pedicle size, and other
      screw parameters (material, diameter). SUMMARY OF BACKGROUND DATA: The in vitro
      screw insertion torque has been correlated to the screw pullout forces and the
      number of cycles to ultimate interface failure. However, there are no comparable
      in vivo data. METHODS: One hundred three pedicle screws were included in the
      study, 43 in vivo and 60 in vitro. Duel-energy x-ray absorptiometry boen mineral
      density data were available for 20 in vivo and 32 in vitro specimens. A custom
      made sterilizable six-axis load cell was integrated into a torque wrench,
      enabling the recording of the applied moments and forces during screw insertion.
      Statistical analysis was performed to detect differences and correlations.
      RESULTS: The mean in vivo insertion torque (1.29 Nm) was significantly greater
      than the in vitro value (0.67 Nm). The linear correlation between insertion
      torque and bone mineral density was significant for the in vitro data but not for
      the in vivo data. No correlation was observed between insertion torque and
      pedicle diameter. Two patterns of torque were observed during the insertion
      process. CONCLUSIONS: There is a significant difference between the insertion
      loads measured in vivo and those measured in vitro. Additional research is needed
      to verify whether this method provides an indication of screw fixation quality.

PMID- 9636976
TI  - Anatomic considerations of anterior transarticular screw fixation for
      atlantoaxial instability.
AB  - STUDY DESIGN: Anatomic parameters of C1 and C2 were measured in 30 dried human
      cervical spines. Anterior transarticular C1-C2 screws were placed in 15 cadaveric
      spines. OBJECTIVE: To provide anatomic data for anterior transarticular
      atlantoaxial screw or C1-C2 screw and plate fixation. SUMMARY OF BACKGROUND DATA:
      A posterior approach to fixation in the atlantoaxial joint has been well
      described. Damage to the vertebral artery is documented as a rare complication of
      posterior atlantoaxial transarticular screw fixation. An anterior surgical
      approach to exposing the upper cervical spine for internal fixation and bone
      graft recently has been developed. No anatomic information regarding the anterior
      transarticular atlantoaxial screw or screw and plate fixation between C1 and C2
      is available in the literature. METHODS: Direct measurements using digital
      calipers and a goniometer were taken from 30 pairs of dried human C1 and C2
      vertebrae. The anterior transarticular C1-C2 screw insertion point is at the
      junction of the lateral edge of the C2 vertebral body to 4 mm above the inferior
      edge of the C2 anterior arch. The parameters related to anterior transarticular
      atlantoaxial screw fixation or screw and plate fixation between the C1 lateral
      mass and the C2 vertebral body were measured. Fifteen embalmed cadavers were used
      for anterior C1-C2 transarticular screw placement. Longer screws (30-40 mm) were
      used to detect whether the screw tips violated the upper cervical canal or
      vertebral arteries. RESULTS: In the anterior transarticular atlantoaxial screw
      placement, lateral angulation of the screw placement relative to sagittal plane
      ranged from 4.8 +/- 1.8 degrees to 25.3 +/- 2.6 degrees. The posterior angulation
      of the screw placement relative to the coronal plane ranged from 12.8 +/- 3.1
      degrees to 22.6 +/- 3.2 degrees. The length of the medial screw path ranged from
      14.7 +/- 1.5 mm to 25.4 +/- 2.8 mm. In the anterior screw and plate fixation, the
      anteroposterior diameter of the inferior facet articular surface ranged from 16.2
      +/- 1.6 mm to 17.1 +/- 1.8 mm. The anteroposterior diameter of the C2 vertebral
      body ranged from 9.3 +/- 1 mm to 16.2 +/- 1.8 mm. The anterior prevascular
      retropharyngeal approach appropriately exposed the atlantoaxial joint for
      anterior transarticular C1-C2 screw placement. No screws violated the vertebral
      artery and cervical canal. CONCLUSIONS: An anterior transarticular atlantoaxial
      screw 15-25 mm long can be inserted with a lateral angulation of 5-25 degrees
      relative to the sagittal plane and a posterior angulation of 10-25 degrees
      relative to the coronal plane. Additionally, in C1-C2 anterior plate fixation
      screws 15 mm long could be anchored in the inferior facet of the C1, and screws 9
      15 mm long could be anchored in the C2 vertebral body.

PMID- 9636977
TI  - Functional turbo spin echo magnetic resonance imaging versus tomography for
      evaluating cervical spine involvement in rheumatoid arthritis.
AB  - STUDY DESIGN: Comparison of findings in plain radiography and conventional
      tomography with findings in plain radiography and magnetic resonance imaging of
      the upper cervical spine in consecutive patients with rheumatoid arthritis and
      with known or suspected abnormalities of the cervical spine. OBJECTIVES: To
      determine whether plain radiography and magnetic resonance imaging provide enough
      information to dispense with tomography in investigations of cervical spine
      involvement in rheumatoid arthritis. SUMMARY OF BACKGROUND DATA: With the recent
      advances in magnetic resonance imaging technology and the proliferation of
      magnetic resonance imaging techniques for specific clinical conditions. METHODS:
      Twenty-eight patients with rheumatoid arthritis and with known or suspected
      abnormalities of the cervical spine underwent a clinical neurologic examination;
      plain radiography, including full flexion lateral radiography; anteroposterior
      and lateral tomography at C1-C2; and magnetic resonance imaging at the same level
      in neutral position and in flexion. Two radiologists evaluated one image set
      consisting of plain radiography and conventional tomographic images and another
      image set consisting of plain radiography and magnetic resonance images, for each
      patient. RESULTS: Compared with conventional tomography and plain radiography,
      magnetic resonance imaging and plain radiography showed cystic lesions and
      erosions of the odontoid process and vertical atlantoaxial subluxation more
      often, showed anterior subluxation as often, and showed lateral atlantoaxial
      subluxation less often. CONCLUSION: Magnetic resonance imaging produces
      sufficiently distinct images of destruction of the odontoid and subluxations for
      it to replace conventional tomography in investigations of upper cervical spine
      involvement in rheumatoid arthritis.

PMID- 9636978
TI  - The radiographic and imaging characteristics of porous tantalum implants within
      the human cervical spine.
AB  - STUDY DESIGN: Seven cadaveric cervical spines were implanted with a porous
      tantalum spacer and a titanium alloy spacer, and their radiographic and imaging
      characteristics were evaluated. OBJECTIVE: To determine the radiographic
      characteristics of porous tantalum and titanium implants used as spacers in the
      cervical spine. SUMMARY OF BACKGROUND DATA: Anterior decompressive surgery of the
      disc space or the vertebral body creates a defect that frequently is repaired
      with autologous bone grafts to promote spinal fusion. Donor site morbidity,
      insufficient donor material, and additional surgical time have spurred the
      development of biomaterials to replace or supplement existing spinal
      reconstruction techniques. Although the promotion of a solid bony fusion is
      critical, the implanted biomaterial should be compatible with modern imaging
      techniques, should allow visualization of the spinal canal and neural foramina,
      and should permit radiographic assessment of bony ingrowth. METHODS: Cadaveric
      spines containing the implants were imaged with plain radiography, computerized
      tomography, and magnetic resonance imaging. The image distortion produced by the
      implants was determined qualitatively and quantitatively. RESULTS: The tantalum
      and titanium spacers were opaque on plain radiographic films. On computed
      tomographic scans, more streak artifact was associated with the tantalum implants
      than with the titanium. On magnetic resonance imaging, the porous tantalum
      implant demonstrated less artifact than did the titanium spacer on T1- and T2
      weighted spin echo and on T2*-weighted gradient-echo magnetic resonance images.
      Overall, the tantalum implant produced less artifact on magnetic resonance
      imaging than did the titanium spacer and therefore allowed for better
      visualization of the surrounding bony and neural structures. CONCLUSION: The
      material properties of titanium and porous tantalum cervical interbody implants
      contribute to their differential appearance in different imaging methods. The
      titanium implant appears to image best with computed tomography, whereas the
      porous tantalum implant produces less artifact than does the titanium implant on
      several magnetic resonance imaging sequences.

PMID- 9636979
TI  - Predictive signs of discogenic lumbar pain on magnetic resonance imaging with
      discography correlation.
AB  - STUDY DESIGN: The correlation between discogenic lumbar pain and disc morphology
      was investigated by using magnetic resonance imaging and discography. OBJECTIVES:
      To assess the various pathologic parameters seen on magnetic resonance imaging in
      patients with discogenic lumbar pain and to correlate them with observations on
      discography. SUMMARY OF BACKGROUND DATA: Although numerous previous studies on
      the subject have been performed, the correlations between various pathologic
      findings on magnetic resonance imaging and pain reproduction by provoked
      discography have not been explained fully. METHODS: One hundred and one lumbar
      discs in 39 patients were studied with magnetic resonance imaging and pain
      provocation discography. When pain reproduction under discography was concordant,
      various pathologic parameters on magnetic resonance imaging were analyzed by
      three statistical parameters to determine the associated magnetic resonance
      imaging findings. RESULTS: Radial tears commonly are demonstrated on magnetic
      resonance imaging in discs with concordant pain on discography. The presence of
      these tears is not a reliable predictor of a painful disc on discography.
      Although a high-intensity zone on T2-weighted images is a relatively reliable
      predictor of pain, the statistical values were lower than those in previous
      studies. Massive degeneration and severe disc height loss were rare in this
      population. These findings were good predictors of pain on disc injection.
      CONCLUSIONS: Although the lumbar intervertebral discs with posterior combined
      anular tears are likely to produce pain, the validity of these signs for
      predicting discogenic lumbar pain is limited.

PMID- 9636980
TI  - Risk of blood contamination of health care workers in spine surgery. A study of
      324 cases.
AB  - STUDY DESIGN: The relative risk of blood contamination during spine surgery was
      studied using data collected from 324 procedures. OBJECTIVES: To analyze
      demographic factors that predict blood-borne pathogens in the population of spine
      surgery patients, study the rates and patterns of blood contamination in health
      care workers (i.e., skin-penetrating incidents and nonpenetrating surface skin
      contamination from patients' blood) and compare those risks with those in other
      surgical departments, and analyze the effectiveness of barrier systems worn by
      the surgical team. SUMMARY OF BACKGROUND DATA: The Centers for Disease Control
      and Prevention has reported 49 health care workers infected by the human
      immunodeficiency virus through occupational exposure. Several studies have noted
      the risk of blood contamination in various surgical departments, but the relative
      risk during spine surgery has not been determined. METHODS: This year-long survey
      included 9795 cases, or 60,789 health care worker--patient contacts, of which
      spine disorders comprised 324 cases (2234 health care workers and patients). Data
      collection forms were designed and inservice training conducted with operating
      room staffs. Information regarding type of case, staff position (surgeon,
      assistant, scrub nurse, circulator), protective clothing worn, length of
      operating room time, blood loss, incidence of blood spills, was recorded, among
      other data. RESULTS: Prevalence of human immunodeficiency virus in patients in
      the overall series was 0.19% versus 0.93% in spine patients. The rate of HCW
      contamination in the overall series was 7.76%, of which 0.92% resulted from skin
      penetrating incidents. Contamination in spine surgery occurred in 31.86% of
      cases, of which 1.23% were the result of skin-penetrating incidents. CONCLUSIONS:
      Health care workers in spine surgery have a statistically significant overall
      higher risk of blood contamination than do those in other surgical departments.
      The increased risk occurred with blood contacting intact skin. There was no
      higher risk for skin penetrating injury. Analysis of data suggests that health
      care workers always should wear double gloves, forearm-reinforced gowns, and eye
      protection.

PMID- 9636981
TI  - The Bagby and Kuslich method of lumbar interbody fusion. History, techniques, and
      2-year follow-up results of a United States prospective, multicenter trial.
AB  - STUDY DESIGN: A prospective, multicenter trial of the Bagby and Kuslich method of
      lumbar interbody stabilization for chronic discogenic low back pain, with follow
      up evaluation at 3 months, 6 months, and yearly thereafter, with independent
      radiographic analysis. OBJECTIVES: To report the history of development, the
      surgical techniques, and results of the Bagby and Kuslich method when used to
      manage discogenic pain of the lumbar spine in humans. SUMMARY OF BACKGROUND DATA:
      Disabling chronic low back pain frequently is resistant to conservative
      management. The "Bagby Basket" effectively has fused the equine and baboon spine.
      The results of biomechanical and animal studies performed over the last 20 years
      have suggested that a similar but improved design--the Bagby and Kuslich device-
      would be useful in stabilizing the human spine. METHODS: From 1992 to 1995, 947
      patients with chronic discogenic low back pain were treated by Bagby and Kuslich
      interbody fusion in a strict, multicenter, prospective clinical trial by using
      either the open anterior or open posterior approach. The study involved 42
      surgeons at 19 medical centers. The authors of the current report analyzed the
      fusion rates, pain relief, functional status, and complications occurring in
      patients who underwent long-term follow-up observation. RESULTS: The Bagby and
      Kuslich method is safe and effective when compared with methods described in
      previous reports of posterior and anterior lumbar interbody arthrodesis performed
      by using bone graft alone. Fusion occurred in 91% of patients at 24 months after
      surgery, and pain was eliminated or reduced in 84%. Function was improved in 91%.
      There were no device-related deaths, cases of major paralyses, device failures,
      or deep infections. CONCLUSIONS: Carefully selected middle-aged patients with
      chronic low back pain secondary to degenerative disc disease can be treated
      effectively and safely by skilled surgeons using the Bagby and Kuslich device for
      one- and two-level interbody fusion.

PMID- 9636982
TI  - Atlantoaxial instability complicating radiation therapy for recurrent
      nasopharyngeal carcinoma. A case report.
AB  - STUDY DESIGN: A case report of a patient in whom atlantoaxial instability
      developed secondary to repeat radiation therapy for recurrent nasopharyngeal
      carcinoma. OBJECTIVES: To illustrate a dramatic and previously unreported
      complication of local radiation to the posterior nasopharynx. SUMMARY OF
      BACKGROUND DATA: Nasopharyngeal carcinoma is an unusual tumor that usually is
      managed with local, external-beam radiation. It is not thought to involve the
      cervical spine directly, although local invasion of the skull base is common.
      METHODS: A review of the medical records and radiographs of the only patient
      known to develop this complication of radiation used to manage nasopharyngeal
      carcinoma. RESULTS: Atlantoaxial instability developed in a patient as a result
      of repeat radiation for a locally recurrent tumor. The instability was associated
      with intrusion of the anterior arch of C1 into the posterior nasopharynx and was
      managed successfully with a posterior stabilization using transarticular screws
      and supplemental wiring. CONCLUSIONS: Patients who have undergone local
      irradiation for nasopharyngeal carcinoma may be at risk for developing
      atlantoaxial instability.

PMID- 9636983
TI  - Traumatic pneumomyelography. A marker of spinal column injury in the face of
      innocuous spine fractures: two case reports.
AB  - STUDY DESIGN: A report of two cases of spinal column injury. OBJECT: To document
      the presence of air within the spinal canal following spinal fractures. SUMMARY
      OF BACKGROUND DATA: Only two previous cases of air in the spinal canal have been
      reported in the English literature. This report emphasizes that even with
      innocuous-appearing fractures of the thoracic spine, a similar phenomenon can
      occur. METHODS: The author reports on the medical records and radiographic
      investigations related to these two cases. RESULTS: Air within the cervical,
      thoracic, and lumbar spine was identified in what appeared to be minor spinal
      fractures of the thoracic spine. CONCLUSIONS: In cases of relatively undisplaced
      fractures of the thoracic spine associated with air in the spinal canal, one
      should be alert to the possibility of more unstable injuries that may have
      undergone significant displacement at the time of the fracture.

PMID- 9636984
TI  - Conservative treatment of acute and chronic nonspecific low back pain.

PMID- 9636985
TI  - [Sick building syndrome and HVAC system: MVOC from air filters].
AB  - Growth and emissions of volatile metabolites of microorganisms on air filters are
      suspected to contribute to health complaints in ventilated rooms. To prove the
      microbiological production of volatile organic compounds (MVOC), concentrations
      of aldehydes and ketones were determined in two large HVAC systems. The in situ
      derivated aldehydes and ketones (as 2,4-dinitrophenyl-hydrazones) were analysed
      by HPLC and UV detection. The detection limit of each compound was 1 ppb (margin
      of error < 10%). Field measurements were carried out before and after the
      prefilters and the main filters, respectively, to investigate whether aldehydes
      and ketones increase in concentration after filters of HVAC systems. First
      results show that the compounds formaldehyde, acetaldehyde and acetone could be
      detected before and after the filters. The concentrations of these VOC after the
      filters were significantly increased--as a mean over twenty measurements--,
      especially as far as filters made of glass fibre are concerned. However the found
      concentrations were low and mostly comparable to outdoor findings. In
      simultaneous laboratory experiments pieces of used filter material of one HVAC
      system and unused filter pieces (for blank values) were examined in small
      incubation chambers to investigate the possible production of MVOC. For the
      incubation a temperature of 20 degrees C and a relative humidity of 95% was
      chosen. In these experiments an almost identical spectrum of compounds
      (formaldehyde and acetone) was found as in the field measurements. The
      concentrations of these compounds were higher in the chambers with the used
      filter pieces. The concentration of acetone ranged up to almost 12 mg/m3.--As our
      field experiments correspond with our laboratory experiments, we assume that the
      microbial production of volatile organic compounds in HVAC systems under
      operating conditions is possible.

PMID- 9636986
TI  - Occurrence of gram-negative bacteria in drinking water undergoing softening
      treatment.
AB  - A study was carried out on the presence of Gram-negative bacteria in the
      municipal waters of Bologna (Italy) undergoing softening using domestic ion
      exchangers with an automatic disinfection mechanism. The softening process was
      seen to cause a 15 fold increase in 22 degrees C and 36 degrees C heterotrophic
      plate counts. There was a 30 fold increase in Gram-negative bacteria and their
      number correlated directly with temperature and inversely with active residual
      chlorine. Organic matter had no effect on bacterial growth. The most commonly
      found bacteria were various species of Pseudomonas (87.6%) (Ps. acidovorans, Ps.
      denitrificans, Ps. fluorescens and Ps. testosteroni) followed by Aeromonas
      hydrophila (5.6%) and Stenotrophomonas (Xantomonas) maltophilia (3.8% in outgoing
      water). Pseudomonas aeruginosa (present in 5.6% of incoming water samples and
      0.4% of outgoing water) and Yersinia enterocolitica (present in 4.3% of incoming
      water samples and 1.1% of outgoing water) did not find favorable conditions for
      growth on the ion exchange resins.

PMID- 9636987
TI  - [Microbiologic/hygienic evaluation of the risk potential of bacteria from soil
      and water sources in combination with biotechnologic risks of soil restoration].
AB  - Biological cleanup-processes removing contaminations from soil and ground-water
      can be carried out "ex-situ" or "in situ". The pollutants are mineralized
      (totally or partly) by microorganisms. The successful application of
      bioremediation techniques often leads to an increase of aerobic and facultatively
      anaerobic bacteria in soil and/or groundwater, a fact that triggered discussions
      about a potential biological risk originating from these microorganisms. In this
      study the identification results of 10,200 microorganisms isolated from 109
      ground-water- and 152 soil-samples of different sites contaminated with mineral
      oil or chlorinated aromatics are evaluated with respect to a possible biological
      risks originating from these microorganisms. According to their biological risk
      potential, 19.2% (1958) of the isolated organisms can be grouped into risk-groups
      II, that means they they are able o cause human disease but it is unlikely that
      they are spread to the community and there is effective prophylaxis or treatment
      available. The majority of isolates (81.8%) are grouped into risk group I,
      meaning that it is very unlikely that they cause a human disease. All these
      microorganisms are either adsorbed to the soil-matrix or within a closed system
      of a water-treatment-plant, so that the risk of infection is very unlikely for
      healthy individuals (regarding possible pathways of infection). The risk
      potential in waste-water-treatment-plants is regarded to be significantly higher
      than in biological soil-cleanup processes, because of the specific origin of the
      bacteria and the possible formation of aerosols.

PMID- 9636988
TI  - [Insertion possibility of 16S-23S space amplification and random amplified
      polymorphic DNA analysis for typing of methicillin-resistant Staphylococcus
      aureus strains in the context of nosocomial infections].
AB  - Within the scope of the present study n = 183 MRSA isolates from the extended
      area of Dusseldorf and n = 93 international MRSA strains from seven different
      countries were typed by pulsed-field gel electrophoresis and two PCR methods
      (RAPD and 16S-23S-spacer amplification). The isolates could be subdivided into 30
      different types by PFGE, into 21 by means of RAPD and 18 by 16S-23S-spacer
      amplification. PFGE had the highest discriminatory potential, however, a combined
      use of the three typing methods allows a more detailed differentiation even of
      those isolates with identical PFGE pattern. Both amplification procedures were
      rapid, easy in handling with reproductable results. For a temporary
      epidemiological analysis within 24 hours, both amplification methods could be
      combined. In case the investigated isolates were still suspected of showing a
      "clonal identity", they should be analysed by additional PFGE (lasting about four
      days). Although the international isolates were chosen by random selection,
      several MRSA strains with identical pattern could be found in different countries
      of the world. Some RAPD-, spacer- and PFGE pattern were constant over many years.
      This reflects a high genetic stability of single strains.

PMID- 9636989
TI  - Nonhemolytic strains of Listeria monocytogenes detected in milk products using
      VIDAS immunoassay kit.
AB  - In December 1995 detection of Listeria monocytogenes Sv 1/2a in milk products
      that were routinely sampled for investigation at the Austrian Federal Food
      Inspection Laboratory (Vienna) led the food manufacturer in question to withdraw
      his product from the market. While one of seven Listeria strains isolated from
      this food product using "VIDAS L. monocytogenes kit" was undoubtedly L.
      monocyotogenes, six strains were nonhemolytic. In classical bacteriology
      haemolysin is used as an important phenotypic property to differentiate L.
      monocytogenes from the apathogenic L. innocua species. Species identification by
      PCR and by Western blotting confirmed that all nonhemolytic strains were indeed
      L. monocytogenes. Our confirmation of nonhemolytic isolates as true L.
      monocytogenes strains underlines the considerable potential of the VIDAS system
      as a specific immunological easy-to-use and automated test kit for detection of
      L. monocytogenes in food products. Whether or not the presence of non-hemolytic
      Listeria monocytogenes in food products justifies legal actions should be
      addressed by the proper authorities.

PMID- 9636990
TI  - Application of automated thermal disinfection instead of sterilisation procedures
      for treatment of rotating dental instruments: efficacy against viruses?
AB  - In dentistry it is of primary importance to take into consideration microbial
      transfer due to the nature of the construction of rotating dental instruments.
      This aspect was the starting point for our research with the question whether or
      not sterilisation is fundamentally necessary for slow and high speed hand pieces
      to make them "safe" out of a virological point of view, or whether a thermal
      disinfection could also possibly be adequate for this purpose. In this context,
      we tested the efficiency of the cleaning and disinfection capacity of an
      automated steam disinfection and sterilisation unit (Sirona Hygiene Center,
      Siemens, AG, Bensheim) intended to the hygienic treatment of dental instruments
      with respect to viruses. In model tests the corresponding instruments were
      experimentally infected with herpes simplex virus type 1 (HSV) and simian
      vacuoling virus (SV40). As indicator systems we used for both cell cultures
      (measurement of the degree of infectiosity) and (for HSV) polymerase chain
      reactions (PCR; determination of viral nucleic acids). In the tests for
      (residual) infectiosity after thermal disinfection (as an isolated step of the
      Hygienic Centre) and also for a combination of cleaning and subsequent thermal
      disinfection (also after protein application), no infectious virus could be found
      in the interior of the slow handpieces and turbines tested. In opposite to this,
      infectious HSV and SV40 could be found after completion of every isolated
      cleaning program in the turbine (in all three ducts) and in the slow handpiece
      (only in the gearbox duct in the case of HSV, and in the case of SV40 also in the
      water and air ducts in very small amounts). The PCR analyses showed that no
      nucleic acids could be found in both instruments (in the air and water ducts)
      following a practice-relevant combination of cleaning and disinfection, but that
      PCR-positive signals were obtained for the larger-volume gearbox and drive and
      return air ducts in 1 or 2 of 3 test samples. The detection of viral nucleic acid
      proves that it is not a matter of complete removal of the infectious agents from
      the instruments, but rather that they are simply inactivated. Since the test
      samples did not show similar amounts of viral nucleic acid, it demonstrates the
      strong influence of the basic parameters (efficiency of the virus contamination,
      flushing conditions and the like). Our experimental model demonstrate that
      thermal disinfection may be adequate to prevent virus contamination of rotating
      dental instruments, while compulsory sterilisation is not mandatory. Further
      studies are necessary to demonstrate whether the present data are applicable for
      rotating dental instruments from other manufactures.

PMID- 9636991
TI  - [Can the DGHM test for the surgical hand disinfection be used to detect residual
      effects?].
AB  - It is investigated if the log reductions measured by the DGHM test for
      examination and evaluation of disinfecting procedures for the surgical hand wash,
      i.e. the short and long term values RFreference, 0h, RFreference, 3h,
      RFpreparation, 0h and RFpreparation, 3h can be used to detect residual effects (a
      remanent action) of the tested preparation. To do this the differences delta RF =
      RF0h-RF3h of reference and tested preparation have been formed which are a
      measure for the bacterial regeneration rate. A remanence index RI = magnitude of
      delta RFreference/magnitude of delta RFpreparation has been specified, which, in
      case RI > 1 indicates a residual effect of the test preparation in relation to
      the reference. The evaluation of 21 testing protocols is showing that the
      calculated remanence indexes are far away from any significance. This is
      attributed on the one hand to the great standard deviations of the log reductions
      and on the other hand to virtually only small residual effects of the tested
      preparations.

PMID- 9636993
TI  - A tetrahedral zinc(II) complex of tris(2-pyridylethyl)amine.
AB  - The zinc ion in the title complex, [N,N'-bis(2-pyridylethyl)-2-(2
      pyridyl)ethylamine-kappa 4N]zinc(II) diperchlorate, [Zn(C21H24N4)](ClO4)2,
      displays a distorted tetrahedral configuration. The Zn-Npy distances range from
      1.979 (5) to 1.999 (5) A, while the Zn-Namine distance is 2.028 (5) A. The Npy-Zn
      Npy and Npy-Zn-Namine angles range from 111.9 (2) to 119.6 (2) degrees and from
      102.3 (2) to 103.4 (2) degrees, respectively. This behavior contrasts with the
      five-coordinate geometry normally observed in tripodal ligands of similar
      structure, and can be ascribed to the presence of weakly-coordinating anions and
      the ligand-metal chelate-ring size.

PMID- 9636992
TI  - [Current data and questions on the carcinogenicity of solid particles of diesel
      engine exhaust and other sources].
AB  - During the last few years, the findings could be confirmed which led to the
      conclusion that very fine solid particles which are not known to have an
      intrinsic toxicity, can induce lung tumours in rats. The carcinogenic potency
      seems to increase parallel to increasing specific surface area and decreasing
      particle size. However, many questions remain open. Organic compounds which
      contain many carcinogenic polycyclic aromatic hydrocarbons (PAH) can explain only
      less than 1% of the carcinogenic effect of diesel exhaust in the rat lung.
      Therefore, the carcinogenicity of diesel exhaust cannot be reduced by an
      oxidizing catalyst. It burns a part of the organic substances adsorbed on the
      surface of the carbonaceous core of diesel particles and thus helps to follow the
      low standard for particles in diesel emissions, but without reduction of the
      carcinogenic potential because it does not reduce the emission of the insoluble
      carcinogenic part of the particles, the elementary carbonaceous core. The search
      for a hypothetical threshold for the carcinogenicity of particles in the rat lung
      aims at the determination of mechanisms which are preconditions for the
      development of a tumour. If certain doses do not induce such lesions they are
      considered safe. Chronic inflammation, proliferation of epithelial cells and
      fibrosis are discussed to be preconditions. However, the pathways which lead to
      inflammation and proliferation could proceed independent of the molecular
      carcinogenesis. Therefore, a cancer risk from diesel particles and other very
      fine particles may occur under environmental conditions. If the positive
      epidemiologic studies are relevant, a lung cancer risk for humans can be
      calculated which is higher than that calculated from inhalation studies with
      rats.

PMID- 9636994
TI  - endo-endo-anti Diels-Alder diadduct of hexachlorocyclopentadiene with 1,6
      dioxacyclodeca-3,8-diene.
AB  - There are two independent molecules of endo-endo-anti
      1,7,8,9,10,16,17,18,19,19,20,20-dodecachloro-4,13-
      dioxapentacyclo[14.2.1.1(7,10).0(2,15).0(6,11)]icosa-8,17-di ene, C18H12Cl12O2,
      in the unit cell with different conformations. In one, the ten-membered ring
      adopts a chair-chair conformation, and in the other, it adopts a distorted chair
      chair conformation. There are near-zero torsion angles at the ring-fusion bonds
      in both forms [1.5 (6) and 8.1 (5) degrees in the chair-chair molecule, and 2.9
      (5) and 2.5 (5) degrees in the distorted chair-chair molecule]. The torsion
      angles about the bonds comprising the sides of the chair-chair are 158.5 (3), 
      160.7 (3), -146.8 (4) and 155.7 (3) degrees, and those of the distorted chair
      chair are 148.0 (3), -146.8 (3), 175.7 (3) and -52.3 (4) degrees. The norbornene
      C=C bonds have lengths of 1.314 (6) and 1.305 (6) A in the chair-chair molecule,
      and 1.309 (6) and 1.318 (6) A in the other. The four dioxolane-system O-C bonds
      have average lengths of 1.411 (5) and 1.421 (5) A in the two independent
      molecules.

PMID- 9636996
TI  - Effects of tumor necrosis factor alpha (TNF alpha) on the phospholipid metabolism
      of Tetrahymena pyriformis.
AB  - The effect of (0.05 ng ml-1 and 0.1 ng ml(-1)) TNF alpha on the phospholipid
      metabolism of Tetrahymena pyriformis was studied. The amount of phosphatidyl
      choline (PC), phosphatidyl inositol (PI), phosphatidic acid (PA), phosphatidyl
      ethanolamine (PE), diacylglycerol (DAG), arachidonic acid (AA) and ceramide was
      higher, but the phosphatidyl inositol 4 phosphate (PIP) and phosphatidyl inositol
      bis-phosphate (PIP2) as well, as sphingomyelin (SM) content was lower in TNF
      alpha-treated cells than in the controls. In the culture medium (secreted forms)
      this situation was reversed. There were differences in the results gained by
      incorporation of [3H]-palmitic acid or 32P into the phospholipids. To control the
      functional effects of TNF alpha in Tetrahymena, the rate of cell division, the
      condensation of chromatin, the viability of cells and morphometrical values have
      been studied. The cytokine reduced cell growth, altered morphometric indices and
      increased chromatin condensation, however cell viability was not influenced. The
      results demonstrate the effects of TNF alpha at a low level of evolution, what is
      realized by changes in the phospholipid metabolism participating in signalling
      pathways.

PMID- 9636995
TI  - Activation and glucagon regulation of mitogen-activated protein kinases (MAPK) by
      insulin and epidermal growth factor in cultured rat and human hepatocytes.
AB  - Many hepatocellular activities may be proximally regulated by intracellular
      signalling proteins including mitogen-activated protein kinases (MAPK). In this
      study, signalling events from epidermal growth factor (EGF) and insulin were
      examined in primary cultured human and rat hepatocytes. Using Western
      immunoblots, rat and human hepatocytes were found to produce a rapid tyrosine
      phosphorylation of the EGF receptor and MAPK following 0.5-1 min exposure to EGF.
      Phosphorylation of p42 and p44 MAPK was observed following 2.5 min exposure to
      EGF. Insulin treatment produced phosphorylation of the insulin receptor beta
      subunit; she phosphorylation was not observed. MAPK phosphorylation corresponded
      with a shift in molecular weight and an increase in kinase activity. Insulin
      dependent activation of MAPK was unequivocally observed only in human
      hepatocytes, though a slight activation was detected in rat. Co-treatment with
      insulin and EGF produced phosphorylation and complete electrophoretic shift in
      molecular weight of MAPK, with an additive or synergistic increase in enzyme
      activity in rat but not human hepatocytes; human hepatocyte MAPK was maximally
      stimulated by EGF alone. Glucagon pretreatment blocked phosphorylation, gel
      mobility shift and kinase activity of MAPK induced by insulin but only partially
      blocked EGF-induced MAPK activation in human hepatocytes. Glucagon also reduced
      the activation of MAPK by EGF in rat hepatocytes. Pre-treatments with forskolin
      or cyclic AMP analogues diminished in the insulin-, EGF- and insulin plus EGF
      dependent activation of MAPK in rat hepatocytes without effecting phosphorylation
      of receptors or MAPK. These results indicate that although EGF and insulin may
      both signal through the MAPK/ras/raf/MAPK pathway, the response for MAPK differs
      between these ligands and between species. Further, in both rat and human,
      glucagon exerts its effects through a cyclic AMP-dependent mechanism at a level
      in the insulin and EGF signal transduction pathways downstream of MAPK but
      promixal to MAPK. The partial inhibition of EGF-induced MAPK phosphorylation by
      glucagon in human hepatocytes provides further evidence for a raf-1-independent
      pathway for activation of MAPK.

PMID- 9636997
TI  - Occurrence of the Crabtree effect in HeLa cells.
AB  - The occurrence of a Crabtree effect in HeLa cells was detected. Some properties
      of pyruvate kinase (PK) were also evaluated. Hexose phosphate, triose-phosphate
      and phosphoenolpyruvate (PEP) significantly decreased the oxygen consumption of
      digitonin-permeabilized HeLa cells, which were oxidizing succinate. The Crabtree
      effect promoted by PEP was concentration-dependent and was lowered by an increase
      of ADP concentration, suggesting a participation of PK. The dependence of
      fructose-1,6-bisphosphate (FDP) by HeLa cell PK was observed. The PK of HeLa
      cells was inhibited by L-alanine only in the absence of FDP, while in the
      presence of the metabolite, an increase in the activity was observed. PK was also
      inhibited in the presence of L-histidine and L-leucine, while L-serine promoted
      activation. L-Cysteine and L-phenylalanine also inhibited the PK of HeLa cells.
      This, together with the sigmoidal character in relation to substrate
      concentration, suggests the presence of the K-type of PK in HeLa cells.

PMID- 9636998
TI  - Activation of bullous pemphigoid antigen gene in mouse ear epidermis by
      ultraviolet radiation.
AB  - Bullous pemphigoid (BP) is an autoimmune blistering disease and is a
      photoaggravated dermatosis, but the mechanism of the aggravation is still
      unknown. Since damage to DNA initiates transcription of some genes, we
      investigated in epidermis of mouse ears the relationship between DNA damage by
      ultraviolet (UV) radiation and BP antigen (BP-Ag) gene activation. For this,
      albino male mice were irradiated with 254 nm wavelength UV for a total dose of
      500 J m-2. At fixed times (0.5, 2, 24, 48 and 72 h) post-UV irradiation, mouse
      ears were cut off, frozen and sectioned. In the sections, it was found that
      immunohistochemically detectable pyrimidine dimers were observed in nuclei of all
      epidermal cells at 0.5 h that were almost repaired by 72 h; a frequency of single
      strand breaks in DNA detected by in situ nick translation started to increase in
      nuclei of all epidermal cell layers at 0.5 h and the increase continued up to 24
      h; mRNA for BP-Ag localized by non-radioactive in situ hybridization appeared in
      nuclei of basal cells at 0.5 h and in both nuclei and cytoplasm at 2 h; and
      immunoreactive BP-Ag started to increase in the basal cell cytoplasm and in the
      basement membrane zone at 2 h. BP-Ag started to accumulate in the basement
      membrane zone at 2 h. It is suggested that UV radiation increased BP-Ag synthesis
      through BP-Ag synthesis through BP-Ag gene activation and that this reaction is a
      factor which aggravates BP following UV irradiation in BP patients.

PMID- 9636999
TI  - Genomic instability associated with myotonic dystrophy does not involve p53
      expression and activity.
AB  - We tested the hypothesis that the instability of the trinucleotide CTG at the
      myotonic dystrophy (DM) locus could be an intrinsic DNA damage recognisable by
      the p53 cell-cycle checkpoint system. p53 mRNA and protein levels were assayed in
      muscle biopsies and fibroblast cell lines of DM patients and unaffected controls.
      No differences in mRNA and protein levels were found between patients and
      controls, regardless of their expansion size. However, in the cells treated with
      adryamicin, p53 protein levels were comparable in DM and control cells. We
      conclude that the CTG trinucleotide expansion within the myotonin gene does not
      activate the p53 surveillance system, at least in adult tissues. The escape of
      trinucleotide expansion from the p53-mediated DNA repair system could explain
      some of the biological characteristics of genome instability.

PMID- 9637000
TI  - A chemical modification of myeloperoxidase and lactoperoxidase with 2-(O
      methoxypolyethylene glycol)-4, 6-dichloro-s-triazine (activated PEG1).
AB  - The modification of myeloperoxidase and lactoperoxidase with 2-(O
      methoxypolethylene glycol)-4, 6-dichloro-s-triazine, an activated polyethylene
      glycol (PEG1), was investigated. The modification caused a shift of the Soret
      band in the light absorption spectrum, from 430 nm to 418 nm in the case of
      myeloperoxidase (native ferric form), and from 412 nm to 406 nm in the case of
      lactoperoxidase (native ferric form). PEG1-modified myeloperoxidase and PEG1
      modified lactoperoxidase both failed to bind with antiserum to the respective
      native enzyme, but both retained respectively 4.5 +/- 0.3 per cent (mean +/- SE,
      n = 5) and 0.6 +/- 0.2 per cent (mean +/- SE, n = 5) of the activities of
      peroxidation of the hydrogen donor o-methoxyphenol in comparison with the native
      enzyme, and 1.5 +/- 0.2 per cent (mean +/- SE, n = 5) and 1.2 +/- 0.2 per cent
      (mean +/- SE, n = 5) of the activities of destruction of fuchsin basic in the
      presence of hydrogen peroxide and a halide, bromide. The pH dependencies of the
      peroxidating activities were almost the same as those of the corresponding native
      enzymes, but both the optimal pHs of the reactions involving the destruction of
      fuchsin basic were shifted by approximately 1.0 pH unit toward neutral pH
      compared with the respective native enzymes.

PMID- 9637001
TI  - The expression of alpha 2 beta 1 integrin and alpha smooth muscle actin in
      fibroblasts grown on collagen.
AB  - The maturation of connective tissue involves the organization of collagen fibres
      by resident fibroblasts. Fibroblast attachment to collagen has been demonstrated
      to involve cell surface receptors, integrins of the beta 1 family. Integrins are
      associated with cytoplasmic actin of microfilaments either directly or through
      focal adhesions. The major actin isoform of fibroblast microfilaments is beta
      actin and to a lesser extent alpha smooth muscle (alpha SM) actin. Cultured human
      dermal fibroblasts derived from adult dermis, newborn foreskin or keloid scar
      were grown on either uncoated or collagen-coated surfaces. The expression and
      synthesis of both alpha 2 beta 1 integrin and alpha SM actin were followed by
      immunohistology and immunoprecipitation. Fibroblasts on uncoated surfaces
      expressed little alpha 2 beta 1 integrin on their surface, while 20 per cent of
      them demonstrated alpha SM actin within microfilaments. Fibroblasts grown on a
      collagen-coated surface minimally expressed alpha SM actin in microfilament
      structures and a majority of the cells were positive for alpha 2 beta 1 integrin
      on their membranes. Using [35S]-methionine incorporation and immunoprecipitation,
      it was shown that fibroblasts grown in uncoated dishes synthesized more alpha SM
      actin than fibroblasts grown on collagen-coated dishes. In contrast, fibroblasts
      grown on collagen coated dishes synthesized more alpha 2 beta 1 integrin compared
      to the same cells grown on uncoated dishes. Fibroblasts maintained on a type I
      collagen upregulate the expression and synthesis of alpha 2 beta 1 integrin, and
      downregulate the expression and synthesis of alpha SM actin.

PMID- 9637002
TI  - Inactivation of urate oxidase by a system composed of lactoperoxidase, hydrogen
      peroxide and bromide.
AB  - Urate oxidase from Candida utilis, an enzyme containing an essential thiol, was
      examined for its sensitivity to lactoperoxidase, an oxidant present in breast
      milk. Upon exposure to a system composed of lactoperoxidase, hydrogen peroxide
      and bromide at moderately alkaline pH, the urate oxidase exhibited comparable
      activity to the untreated enzyme; but upon exposure at moderately acidic pH, it
      lost its activity completely. Thus the lactoperoxidase-H2O2-bromide system
      significantly inactivated urate oxidase only at moderately acidic pH. This
      inactivation was prevented by the presence of N-acetylmethionine, a methionine
      analogue, or glutathione, which is a thiol compound analogous to an amino acid,
      indicating that it was probably due to the oxidation and damage of the methionine
      residue and/or the thiol group in the urate oxidase by the lactoperoxidase
      system, that loss of catalytic activity of the urate oxidase occurred.

PMID- 9637003
TI  - Ribosomes mask cytochrome b5 on rough microsomal vesicles.
AB  - Cytochrome b5 is unmasked on the removal of ribosomes by chemical degranulation
      of rat liver microsomes. Reattachment of ribosomes to stripped membranes remasks
      this enzyme on the membrane surface. This haemoprotein may be involved either in
      the attachment of ribosomes to reticular membranes or in protein biosynthesis by
      membrane-bound ribosomes.

PMID- 9637004
TI  - Levels of toxaphene indicator compounds in fish meal, fish oil and fish feed.
AB  - Three toxaphene indicator compounds were determined in fish oil and fish meal of
      different origin and raw material as well as in feed containing fish oil and fish
      meal. Fish oil and fish meal from South America contained no or only traces of
      the indicator congeners. The sum of the three compounds varied in fish oils from
      Europe between 13 micrograms/kg fat (sand eel oil) and 206 micrograms/kg fat (cod
      oil). Varying concentrations were also determined in European fish meal and in
      feed. Toxaphene indicator compounds were as well detected in trout and salmon fed
      with toxaphene residues containing feed. Results indicate that feed can
      contribute to toxaphene contamination of farmed salmon from Europe.

PMID- 9637005
TI  - Organochlorine pesticides and PCBs in human milk collected from mothers nursing
      hospitalized children.
AB  - Organochlorine compounds in milk were analyzed in samples collected over a nine
      year period (1987-1995) from nursing mothers (N = 139) whose children were
      hospitalized for various disorders. All samples contained p,p'-DDE and PCBs; the
      median concentrations were 318 micrograms/kg milk fat and 220 micrograms/kg milk
      fat resp. Higher levels were found in mothers (N = 12) nursing neonates with
      impaired neurodevelopmental competencies or an inappropriate arousal reaction. No
      difference was observed between mothers nursing children with respiratory or
      gastrointestinal diseases, urinary tract infections or other infectious diseases,
      anemias, prolonged neonatal hyperbilirubinaemias or when children were with
      dermatological findings, congenital malformations or healthy.

PMID- 9637006
TI  - Pentachlorophenol and phenanthrene biodegradation in creosote contaminated
      aquifer material.
AB  - Contamination of the subsurface environment at the Libby Superfund Site, Montana,
      includes polycyclic aromatic hydrocarbons and f1p4achlorophenol due to accidental
      spills and improper disposal of wood preserving wastes. Biodegradation is a
      treatment technology gaining wide application in the treatment of hazardous waste
      sites. A microcosm study was conducted to evaluate the effect of temperature,
      sampling depth, nutrient addition, and oxygen on the biodegradation potential of
      phenanthrene and pentachlorophenol in aquifer samples using radiolabeled
      chemicals. Mineralization of phenanthrene reached 14% but was less than 1% for
      pentachlorophenol over the 56 day incubation period. Phenanthrene mineralization
      in microcosms at 10 degrees C was not significantly different from those at 20
      degrees C. This may have been due to microbial community acclimation to lower
      temperatures at the site. Average volatilization was less than 2% for both
      phenanthrene and pentachlorophenol. After 56 days, most of the radiolabeled
      chemical was either solvent extractable or soil bound.

PMID- 9637007
TI  - Application of an automated HS-GC method in partition coefficient determination
      for xylenes and ethylbenzene in rat tissues.
AB  - An automated static head space-gas chromatography method was used in the
      determination of partition coefficients (Kd) for the xylene isomers and
      ethylbenzene in blood, brain, muscle, kidney, liver and fat of Sprague Dawley
      rats. Since homogenization resulted in the potential loss of analytes from tissue
      samples, unhomogenized samples were used. With a few exceptions, tissue:air Kd
      values were independent of the concentrations of the analytes, singly or as a
      mixture. The tissue:blood Kd values were determined. For each tissue and analyte,
      the value obtained for each analyte concentration was within +/- 10% of the mean
      value calculated for the entire concentration range.

PMID- 9637008
TI  - Methanogenic bacteria: presence in foodstuffs.
AB  - Methanogenic bacteria are anaerobic, oxygen-intolerant microorganisms, and it is
      only by studying the different habitats of such bacteria that fundamental
      information about their ecology becomes available. This research has evaluated
      methanogenic bacteria in apparently aerobic ecosystems, in foodstuffs not
      subjected to chemical-physical reclamation processes, where the presence of
      methanogenic bacteria has never been investigated. Methanogenic bacteria,
      ascribable to the Methanogenium, Methanobacterium and Methanosarcina genera, were
      found in vegetables, meat, fish and cheese but were generally absent in
      confectionery products and fruit. The microorganisms appear to be chance
      contaminants, usually being present in only very low numbers. It should be noted
      that none of the tested foods showed the presence of Methanobrevibacter smithii,
      M. oralis or Methanosphaera stadtmaneae, methanogenic bacteria sometimes present
      in the human digestive tract.

PMID- 9637009
TI  - Effect of different starches on Escherichia coli (S1) beta-glucuronidase
      expression.
AB  - Studies with pure cultures growing in laboratory media indicated that beta
      glucuronidase expression of Escherichia coli S1 was considerably affected by
      starch added to the medium as the only carbon source. This result, which may be
      an aspecific modulation of enzyme expression, was independent of the starch
      molecular structure and effects were analogous for maize, rice, wheat or potato
      starches. It was observed that enzyme expression was little affected by the
      growth rate. The beta-glucuronidase activities of starch-grown bacteria found in
      the present study agree with those observed in animal and human models performed
      for in vivo evaluation of effects of dietary starch effects on gut microbial
      ecosystems.

PMID- 9637010
TI  - New shuttle vectors for Rhodococcus sp. R312 (formerly Brevibacterium sp. R312),
      a nitrile hydratase producing strain.
AB  - Two shuttle vectors named pRC52 (10.7 Kb) and pRK52 (12.2 Kb) carrying
      chloramphenicol (Cm) and chloramphenicol plus kanamycin (Km) resistance genes,
      respectively, were constructed by fusion of a cryptic plasmid pBL13869 (replicon
      pBL1, 5.8 Kb) from Brevibacterium lactofermentum ATCC13869 with pBR328 E. coli
      plasmid. Transformation of Rhodococcus sp. R312 (formerly Brevibacterium sp.
      R312) protoplasts was realised with an efficiency of 28 transformants per
      micrograms of DNA.

PMID- 9637011
TI  - Effect of osmotic stress on glucose oxidase production and secretion by
      Aspergillus niger.
AB  - A mycelium of Aspergillus niger was cultured under various osmotic stresses. When
      fungus was cultured under osmotic stress, total catalase activity increased with
      increasing concentration of NaCl, up 0.4 M, but glucose oxidase under this
      condition significantly decreased. Mycelial growth was repressed with increased
      media osmolarity. To release periplasmic glucose oxidase 72-h old mycelium was
      suspended on a concentrated solution of NaCl (0.4-2.8 M/l). The highest yield of
      GOD activity was obtained at a NaCl concentration of 1.2 M at pH 6.0, which
      improved the activity of this enzyme by about 2.1-fold in comparison with the
      control medium without this depressor.

PMID- 9637012
TI  - Continuous ethanol production from sugarcane molasses using a column reactor of
      immobilized Saccharomyces cerevisiae HAU-1.
AB  - A fermentation system for the continuous ethanol production from sucrose and
      molasses using calcium alginate immobilized Saccharomyces cerevisiae strain HAU-1
      has been optimised. Immobilization of active yeast cells (30%, w/v) was
      accomplished in 1.5% calcium alginate and these yeast-beads were employed for
      ethanol production in a vertical column reactor. High ethanol productivity was
      achieved with a medium containing 10%, w/v sucrose at a dilution rate of 0.20 h
      1. Alginate beads containing 30-50% yeast cell--mass resulted in high
      productivity 60.4 g l-1 h-1). Sugarcane molasses containing 15% total sugars was
      fermented in column reactor to produce 6.0%, v/v ethanol in continuous system.
      These yields could be improved to 7.0% with overall 11% increase in fermentation-
      efficiency with the use of acid-clarified sugar cane molasses medium.

PMID- 9637013
TI  - The isolation of Pseudomonas and other Gram(-) psychrotrophic bacteria in raw
      milks.
AB  - In this research, totally 200 raw milk samples in different areas of Ankara were
      collected from various dairy plant. The isolated psychotrophic bacteria from the
      raw milk samples are the species of Pseudomonas spp., Acinetobacter spp.,
      Alcaligenes and Aeromonas. Isolation of Pseudomonas and other gram(-)
      psychrotrophic bacteria types are determined as P. aeruginosa 11 (5.5%), P.
      putida 11 (5.5%), P. fluorescens biotype I 10 (5.0%), P. fluorescens biotype II 4
      (2.0%), P. fluorescens biotype III 6 (3.0%), P. aurefaciens 2 (1.0%), P.
      pseudomallei 3 (1.5%), P. cepacia 1 (0.5%), A. calcoaceticus lowffii 5 (2.5%), A.
      calcoaceticus anitratum 4 (2.0%), A. faecalis 3 (1.5%) and A. hydrophilia 1
      (0.5%).

PMID- 9637014
TI  - Toxin production by pathovars of Pseudomonas syringae and their antagonistic
      activities against epiphytic microorganisms.
AB  - 75 strains of 21 various Pseudomonas syringae (P.) pathovars were investigated in
      different tests for their toxin production. Data from literature about the
      production of the known phytotoxins phaseolotoxin (pv. phaseolicola), tabtoxin
      (pv. coronafaciens, pv. tabaci), coronatine (pv. atropurpurea, pv. glycinea, pv.
      maculicola, pv. morsprunorum, pv. tomato), and toxins of the lipodepsipeptide
      group (pv. aptata, pv. atrofaciens, pv. syringae) could be confirmed. Besides, a
      production of the phytohormone ethylene was detected for P. phaseolicola isolates
      from kudzu (Pueraria lobata) and for all tested P. glycinea and P. cannabina
      strains. Strains of P. apii, P. aptata, P. atrofaciens, and P. tomato produced
      antimetabolic toxins which could be detected with an agar diffusion assay with
      Escherichia coli as indicator strain. These antimetabolites inhibit a step in the
      arginine/ornithine biosynthesis. P. maculicola strains caused inhibition zones in
      this assay which could not be reversed by the tested amino acids. All strains
      with inhibitory effect against E. coli and Geotrichum candidum were also proved
      for their antagonistic activity against a selection of typical phyllosphere
      microorganisms. Most of the phytotoxins possess antimicrobial activity with
      different spectrum and efficiency. Only the lipodepsipeptide-producers showed
      antifungal activities. Our results show that the production of toxins is a
      widespread property among Pseudomonas syringae pathovars, and that some pathovars
      can produce more than one toxin. This characteristic and the antimicrobial
      activity of most toxins could be of advantage for the toxin-producing bacteria to
      adapt to different habitats.

PMID- 9637015
TI  - Partial purification of an iron-dependent L-serine dehydratase from Clostridium
      sticklandii.
AB  - An oxygen-sensitive and highly unstable L-serine dehydratase was partially
      purified from the Gram-positive anaerobe Clostridium sticklandii. The final
      active preparation contained five proteins of 27, 30, 44.5, 46, and 58 kDa as
      judged by SDS-PAGE. The N-terminal sequence of the 30 kDa subunit showed some
      similarity to the alpha-subunits of the iron-containing L-serine dehydratases
      from Clostridium propionicum and Peptostreptococcus asaccharolyticus. Oxygen
      inactivated L-serine dehydratase from C. sticklandii was reactivated by
      incubation with Fe2+ under reducing conditions. Furthermore, the enzyme was
      inactivated by iron-chelating substances like phenanthroline and EDTA. Pyridoxal
      5-phosphate (PLP) did not stimulate the activity, and known inhibitors of PLP
      containing enzymes such as NaBH4 had no effect on the activity of L-serine
      dehydratase from C. sticklandii.

PMID- 9637016
TI  - Determination of histamine and leukotrienes from basophils in cell supernatants
      by high-performance liquid chromatography.
AB  - A reversed-phase high-performance liquid chromatographic method with gradient
      elution for the separation of the mediator substances histamine and the
      leukotrienes C4 (LTC4), D4 (LTD4), and E4 (LTE4) is described. The detection
      occurs fluorimetrically after automated precolumn derivatization with o
      phthaldialdehyde. All components are chromatographically separable. Because of
      the different excitation and emission wavelengths, only the most important
      biological active mediators histamine and LTC4 are determinable in one parallel
      chromatographic run. The method is examined by linearity and precision tests and
      is applicable to biological sample matrices like cell supernatants of human
      basophils enriched by Percoll-density gradient centrifugation and stimulated for
      mediator release by anti-IgE. The established method is suitable to separate the
      mediators from other matrix components. The determination limit for histamine is
      55.0 micrograms/L and that for LTC4 16.0 micrograms/L, referring to the reference
      solutions. Therefore, a fast, economical method for the common determination of
      the most important mediators histamine and LTC4 is established. This method is
      also suitable for high sample amounts in routine medical analysis.

PMID- 9637017
TI  - Isolation and recovery of 2-aminoethanol, N-methyl-2-aminoethanol, and N,N
      dimethyl-2-aminoethanol from a copper amine aqueous matrix and from amine-treated
      sawdust using liquid-liquid extraction and liquid-solid extraction combined with
      capillary gas chromatography-ion-trap mass spectrometry.
AB  - An analytical method for the rapid isolation and recovery of the homologous
      series of 2-aminoethanols, a class of organic compounds of importance to wood
      preservative treatment, is successfully developed. The method is applied to an
      aqueous solution of copper amine (copper[II] hydroxide complexed
      monoethanolamine) and to copper-amine-treated sawdust. The method incorporates a
      gas chromatograph-ion-trap mass spectrometer. A discussion of the secondary
      equilibrium effects involved when ionizable analytes are extracted from an
      aqueous phase with respect to organic bases is presented. Using 2-propanol as the
      extractant coupled to a salt-saturated aqueous phase results in recoveries of 63%
      for 2-aminoethanol, 51% for N,N-dimethyl-2-aminoethanol, and 56% for N-methyl-2
      aminoethanol for a single liquid-liquid extraction. The choice of 2,2,2
      trifluoroethanol as an internal standard is found to be quite suitable. A
      comparison of the precision and accuracy for an external versus an internal mode
      of instrument calibration demonstrates that the internal standard mode is
      preferable for this manual injection.

PMID- 9637018
TI  - High-performance liquid chromatographic analysis with diode-array detection of
      bradykinin, neuropeptide K, and substance P in human plasma.
AB  - A method is described for the determination of bradykinin, neuropeptide K (NPK),
      and substance P in patients with atypical carcinoid syndrome. The developed
      method uses a combination of conventional and solid-phase extraction as well as
      high-performance liquid chromatographic techniques. A narrow-bore C18 column with
      ultraviolet detection is used (200 nm). The technique recovers bradykinin at a
      level of 98%, NPK at 96%, and substance P at 98% (when pure standards are
      dissolved) at concentration levels relevant to the atypical carcinoid syndrome.
      In biological samples, the recovery rate of bradykinin, NPK, and substance P
      drops to 88, 86, and 88% respectively. The overall analysis time is 150 min from
      receipt of samples. This method proves to be a valuable tool in the
      identification of neuropeptides and thus the diagnosis of atypical carcinoid
      syndrome, especially in puzzling cases with nonspecific symptoms.

PMID- 9637019
TI  - The magic of hypnosis: is it child's play?
AB  - Hypnosis is often disregarded and undervalued because it cannot be currently
      explained by natural science or scientific method. An alternative existential
      psychology paradigm, specifically an existential-phenomenological model, is
      offered here to close the gap between the theoretical and the actual clinical
      practice of hypnosis. This existential-phenomenological model emphasizes the
      individual's experience over any preconceived notions or diagnoses. In this
      context, the author introduces and discusses the idea that perception prefigures
      embodiment, creating the power of suggestion. And children's greater overall
      hypnotic susceptibility is explained as a result of natural unbiased observations
      of the world, free of the mind-body split that adults apply to perception.

PMID- 9637020
TI  - Time perspective: temporal extension, time estimation, and impulsivity.
AB  - It has been proposed that time perspective is an important variable that can, in
      part, explain the differences between people in terms of the development of self
      control. One corollary of this position is that time perspective is somehow
      related to systematic biases in the way people perceive the passage of time. Such
      a bias may or may not be augmented by an association between time perspective and
      impulsivity. Two studies were conducted using measures of temporal extension,
      time estimation, and impulsivity. In general, no consistent effects were found.
      Neither time perspective nor impulsivity was related to any characteristic
      pattern of errors. In the second study, time perspective (mediated by age) was
      associated with predicting very brief time estimation scores, but not longer time
      estimation periods. It was concluded that whatever the mechanism might be that
      underlies the purported effect between time perspective and self-control, it is
      not related to a differential ability to perceive time moving more or less
      quickly.

PMID- 9637021
TI  - Attitudinal predictors of dissociation: hostility and powerlessness.
AB  - The relationship between dissociative tendencies and attitudes relating to
      aggression and powerlessness was investigated in a sample of 106 Australian
      psychology students. Dissociation was positively related to aspects of aggression
      and in particular to an attitude of hostility. Respondents' perceptions of their
      own powerlessness did not predict proneness to dissociative experiences. The data
      are consistent with the view that trauma-engendered attitudes and affects may be
      markers of the development of dissociative tendencies.

PMID- 9637022
TI  - Self-Deceptive Enhancement and Impression Management correlates of EPQ-R
      dimensions.
AB  - The Self-Deceptive Enhancement and Impression Management scales of the Paulhus
      (1991) Balanced Inventory of Desirable Responding were correlated with the
      Psychoticism, Neuroticism, Extraversion, and Lie scales of the Eysenck EPQ-R
      (Eysenck & Eysenck, 1991) in a student sample. Extraversion correlated positively
      and Neuroticism correlated negatively with Self-Deceptive Enhancement, whereas
      Psychoticism correlated negatively and the Lie scale correlated positively with
      Impression Management. These findings suggest that the EPQ-R scales are involved
      in different aspects of socially desirable responding. It was concluded that
      social desirability should not be controlled in measures of Extraversion and
      Neuroticism but it should be controlled in measures of Psychoticism.

PMID- 9637023
TI  - Physiological mechanisms of sexual dysfunction side effects associated with
      antidepressant medication.
AB  - Sexual dysfunction side effects have been associated with antidepressant
      medication, especially with serotonin reuptake inhibitors. Neurotransmitters
      appear to be involved, especially dopamine and serotonin, but the processes by
      which they influence sexual dysfunction are not clear.

PMID- 9637024
TI  - Predictors of aggression in hospitalized adolescents.
AB  - Client records spanning a 14-month period were examined for an adolescent unit of
      a large state psychiatric hospital to identify client variables predictive of
      acts of physical aggression in hospitalized adolescents. Forty-two percent of the
      43 girls and 55% of the 57 boys were classified as aggressive because they had
      committed at least one act of physical aggression during the data collection
      period. In logistic regression analyses, client characteristics were used to
      predict aggression classification and 79%, 81%, and 92% of the total sample,
      girls, and boys, respectively, were correctly classified. Aggression in the girls
      was associated with having a history of family violence, being of a minority
      race, and being on medication; for the boys, aggression was associated with a
      diagnosis of a conduct disorder, being on medication, and being previously
      hospitalized.

PMID- 9637025
TI  - Physiological studies of the precedence effect in the inferior colliculus of the
      kitten.
AB  - The precedence effect (PE) is a perceptual phenomenon that reflects listeners'
      ability to suppress echoes in reverberant environments. The PE is not present at
      birth and appears only several months postnatal. Recent physiological studies
      have demonstrated correlates of the PE in the central nucleus of the inferior
      colliculus (ICC) of adult animals. The present study extended the same techniques
      to search for similar correlates in the ICC of kittens during the first postnatal
      month. Stimuli consisted of pairs of clicks or noise bursts presented from
      different locations in free field or with different inter-aural differences in
      time (ITD) under headphones, with an inter-stimulus-delay (ISD) between their
      onsets. Results suggest that a physiological correlate of the PE, i.e.
      suppression of responses to the second source, is present as early as 8 days
      postnatal, and occurs at similar ISDs to those recorded in adult cats.
      Suppression in kitten neurons varies with stimulus level, duration, and azimuthal
      position, in a similar manner to that in adult neurons. The age at which
      correlates of the PE in the kitten can be found precedes the age at which kittens
      can localize sound sources effectively, and presumably before the age at which
      they would demonstrate the PE behaviorally. Thus, the neural mechanisms that
      might be involved in the first stages of processing PE stimuli may be in place
      well before the behavioral correlate develops.

PMID- 9637026
TI  - Voice F0 responses to manipulations in pitch feedback.
AB  - Recent studies have shown that when phonating subjects hear their voice pitch
      feedback shift upward or downward, they respond with a change in voice
      fundamental frequency (F0) output. Three experiments were performed to improve
      our understanding of this response and to explore the effects of different
      stimulus variables on voice F0 responses to pitch-shift stimuli. In experiment 1,
      it was found that neither the absolute level of feedback intensity nor the
      presence of pink masking noise significantly affect magnitude or latency of the
      voice F0 response. In experiment 2, changes in stimulus magnitude led to no
      systematic differences in response magnitudes or latencies. However, as stimulus
      magnitude was increased from 25 to 300 cents, the proportion of responses that
      changed in the direction opposite that of the stimulus ("opposing" response)
      decreased. A corresponding increase was observed in the proportion of same
      direction responses ("following" response). In experiment 3, increases in pitch
      shift stimulus durations from 20 to 100 ms led to no differences in the F0
      response. Durations between 100 and 500 ms led to longer duration voice F0
      responses with greater response magnitude, and suggested the existence of a
      second F0 response with a longer latency than the first.

PMID- 9637027
TI  - Measurements of differential scattering cross section using a ring transducer.
AB  - A procedure for the measurement of intrinsic scattering object properties is
      presented and used to obtain illustrative results. The procedure is based on the
      measurement of the scattered acoustic field as a function of scattering angle and
      frequency. Measurements are normalized using analytically determined expressions
      for emitter and detector beams resulting from a combination of unfocused linear
      elements arranged in a circular configuration. The spatial effects of finite
      emitter pulse length and detector gate length are represented by a convolution
      formula valid for narrow-band transmitted signals and long receiver gates. The
      normalization includes correction for target absorption as well as measurement of
      the directly transmitted acoustic power in the free field and yields the average
      differential scattering cross section per unit volume. Under the Born
      approximation, this quantity is directly proportional to the spatial-frequency
      spectrum of the scattering medium inhomogeneities. Measured results are reported
      for two phantoms consisting of glass microspheres embedded in a weakly absorbing
      agar background medium. For the phantoms employed, scattering effects, rather
      than increased absorption, are shown to account for most of the difference in
      transmission loss between pure agar and agar with glass spheres. The measured
      differential scattering cross sections are compared with theoretical cross
      sections for distributions of glass spheres measured experimentally. The measured
      values show good relative agreement with theory for varying angle, frequency, and
      phantom properties. The results are interpreted in terms of wave space resolution
      and the potential for tissue characterization using similar fixed transducer
      configurations.

PMID- 9637028
TI  - Predicting hearing aid response in real ears.
AB  - A hearing aid fitted to different ears will produce very different sound pressure
      spectra in the ear canal. In addition, this variation in response is different
      among hearing aids. A description in terms of an electrical analog model of the
      ear and hearing aid system is given. The applicability of this model is tested
      through series of measurements. The measurement and prediction procedure was
      first verified on a coupler (ear simulator) with good results from 300 to 8000
      Hz. Three types of hearing aids were then measured and used on five different
      human ears. Where the measured and predicted response was compared a fairly good
      agreement was obtained from 300 Hz to approximately 6000 Hz. A major source of
      error is probe misalignment. The theoretical description given in the present
      work is likely to be valid from low frequencies to at least 10 kHz. Although
      solutions for related problems have been given for low frequencies, a solution of
      the hearing aid fitting problem at high frequencies has not been published
      earlier.

PMID- 9637029
TI  - Growth behavior of the 2 f1-f2 distortion product otoacoustic emission in
      tinnitus.
AB  - High-resolution hearing threshold and 2 f1-f2 distortion product otoacoustic
      emission (DP) were measured with the same in-the-ear sound probe and same
      calibration at 51 frequencies between 500 and 8000 Hz in 39 sensorineural hearing
      loss ears associated with tinnitus. Using a primary tone setting L1 = 0.4L2 + 39
      that accounts for the nonlinear interaction of the two primary tones at the DP
      generation site at f2, DPs were elicited in a wide range from L2 = 65 to 20 dB
      SPL. We failed to find a uniform DP behavior in the 39 tinnitus ears tested.
      Seventeen of them behaved like impaired ears without tinnitus. In these ears a
      linearized DP growth was observed where the DP level decreased and the slope of
      the DP I/O functions steepened with increasing hearing loss and as a result both
      the DP level and the DP slope strongly correlated with hearing threshold. The
      other population, 22 tinnitus ears, exhibited a poor or even inverse relationship
      between DP level and hearing threshold, i.e., displayed an increase of DP level
      with increasing hearing loss. Despite the severe hearing loss but due to the high
      level, DPs could be recorded well in the frequency range that corresponded to the
      appearance of the tinnitus. The DP slope, however, increased with increasing
      hearing loss and, therefore, did still correlate with hearing threshold revealing
      pathological alteration. The data suggest that the DP level alone is hardly
      capable of assessing hearing impairment in tinnitus ears and may even be
      misleading. Thus just the DP slope seems to be the only reliable indicator of
      cochlear malfunction around the tinnitus frequency. The observed nonuniform DP
      behavior suggests different cochlear impairments in tinnitus ears. In those ears
      where the DP level decreases and the slope of the I/O functions increases with
      hearing loss, cochlear sensitivity and tuning are supposed to be diminished. In
      those ears where the DP level increases with increasing hearing loss, a
      reinforced mechanical distortion is hypothetized to be generated by cochlear
      hyperactivity that can be the source of both the abnormally high DP level and the
      tinnitus.

PMID- 9637030
TI  - The level and growth behavior of the 2 f1-f2 distortion product otoacoustic
      emission and its relationship to auditory sensitivity in normal hearing and
      cochlear hearing loss.
AB  - The 2 f1-f2 distortion product otoacoustic emission (DP) was measured in 20
      normal hearing subjects and 15 patients with moderate cochlear hearing loss and
      compared to the pure-tone hearing threshold, measured with the same probe system
      at the f2 frequencies. DPs were elicited over a wide primary tone level range
      between L2 = 20 and 65 dB SPL. With decreasing L2, the L1-L2 primary tone level
      difference was continuously increased according to L1 = 0.4L2 + 39 dB, to account
      for differences of the primary tone responses at the f2 place. Above 1.5 kHz, DPs
      were measurable with that paradigm on average within 10 dB of the average hearing
      threshold in both subject groups. The growth of the DP was compressive in normal
      hearing subjects, with strong saturation at moderate primary tone levels. In
      cases of cochlear impairment, reductions of the DP level were greatest at lowest,
      but smallest at highest stimulus levels, such that the growth of the DP became
      linearized. The correlation of the DP level to the hearing threshold was found to
      depend on the stimulus level. Maximal correlations were found in impaired ears at
      moderate primary tone levels around L2 = 45 dB SPL, but at lowest stimulus levels
      in normal hearing (L2 = 25 dB SPL). At these levels, 17/20 impaired ears and
      14/15 normally hearing ears showed statistically significant correlations. It is
      concluded that for a clinical application and prediction of the hearing
      threshold, DPs should be measured not only at high, but also at lower primary
      tone levels.

PMID- 9637031
TI  - Observing middle and inner ear mechanics with novel intracochlear pressure
      sensors.
AB  - Intracochlear pressure was measured in vivo in the base of the gerbil cochlea.
      The measurements were made over a wide range of frequencies simultaneously in
      scalae vestibuli and tympani. Pressure was measured just adjacent to the stapes
      in scala vestibuli and at a number of positions spaced by tens of micrometers,
      including a position within several micrometers of the basilar membrane, in scala
      tympani. Two findings emerged from the basic results. First, the spatial
      variation in scala tympani pressure indicated that the pressure is composed of
      two modes, which can be identified with fast and slow waves. Second, at
      frequencies between 2 and 46 kHz (the upper frequency limit of the measurements)
      the scala vestibuli pressure adjacent to the stapes had a gain of approximately
      30 dB with respect to the pressure in the ear canal, and a phase which decreased
      linearly with frequency. Thus, over these frequencies the middle ear and its
      termination in the cochlea operate as a frequency independent transmission line.
      A subset of the data was analyzed further to derive the velocity of the basilar
      membrane, the pressure difference across the organ of Corti complex (defined to
      include the tectorial and basilar membranes) and the specific acoustic impedance
      of the organ of Corti complex. The impedance was found to be tuned in frequency.

PMID- 9637032
TI  - Paradoxical relationship between frequency selectivity and threshold sensitivity
      during auditory-nerve fiber development.
AB  - The acquisition of adult-like frequency selectivity is generally assumed to be
      the tightly coupled to improvements in threshold sensitivity during cochlear
      development. In this study, frequency versus threshold (tuning) curves obtained
      from 1108 auditory-nerve fibers were used to investigate the relationship between
      tuning and threshold at characteristic frequency (CF) during postnatal
      development in kittens. At the earliest ages included in this study, sharpness
      was within the adult range, but thresholds were significantly higher than adult
      values. Tuning and thresholds improved along different exponential time courses
      that varied with CF. For units with CFs below 1 kHz, tuning curve slopes below CF
      matured earliest, followed by CF threshold, and then by slopes above CF. In
      contrast, for CFs above 1 kHz, the high-frequency slopes matured first, followed
      by threshold and then by slope below CF. One interpretation of these results is
      that tuning and thresholds are not tightly coupled in immature animals.
      Paradoxically, however, high-frequency slopes were correlated with threshold for
      individual units at all ages, suggesting that the relationship between tuning and
      threshold is maintained during development. This contradiction can be resolved by
      a developmental model that features a functional separation between cochlear
      nonlinearities and mechanical/electrical conversion.

PMID- 9637033
TI  - Interrupted noise exposures: threshold shift dynamics and permanent effects.
AB  - A parametric study of the reduction of threshold shift (toughening phenomena)
      that takes place during the course of an interrupted noise exposure is described.
      266 chinchillas randomly assigned to one of 32 experimental groups were exposed
      to one of the following: a 400-Hz narrow-band impact noise having a center
      frequency of 0.5, 1.0, 2.0, 4.0, or 8.0 kHz and peak sound-pressure levels of
      109, 115, 121, or 127 dB. The impacts were presented for 5 d, 24 h/d or for 20 d,
      6 h/d. corresponding pairs of exposures had equal energy. Group mean noise
      effects were estimated from pure-tone threshold obtained form inferior colliculus
      evoked potentials and from surface preparation histology. The threshold shift
      (TS) toughening phenomena is shown to occur in response to all stimuli that
      produce a TS and at all audiometric test frequencies. The amount of toughening,
      which is limited to less than 35 dB, varies with noise frequency and intensity.
      Based on group mean data the auditory system is not protected from the permanent
      effects of an interrupted noise exposure as a result of the toughening effect but
      rather differences in permanent effects between the 5- and 20-d exposures are
      attributed to the spreading of the exposure energy over an extended period of
      time.

PMID- 9637034
TI  - Double-evoked otoacoustic emissions. II. Intermittent noise rejection,
      calibration and ear-canal measurements.
AB  - Measurements of double-click-evoked otoacoustics emissions (2CEOAEs) and double
      chirp distortion products (2ChDPs) are reported for normal-hearing adults based
      upon theory presented in an earlier report [Keefe, J. Acoust, Soc. Am. 103, 3489
      3498 (1998)]. The nonlinear acoustic response of a probe assembly used in ear
      canal measurements in tested in a calibration cavity to compare the double-evoked
      (2E) technique with existing OAE techniques. The 2E technique reduces the peak
      distortion by approximately 30 dB relative to existing click-evoked techniques.
      The 2E subtraction of click responses is partially analogous to current
      techniques in that the linear response is eliminated, but differs in that high
      frequency measurements are improved by eliminating time gating of the cochlear
      response, and low-frequency measurements are improved by reducing probe
      distortion, especially when two acoustic sources are used. Because time gating is
      eliminated, it is straightforward to measure the onset of a click-evoked OAE. The
      nonlinear coherence function is used to measure the nonlinear distortion signal
      to-noise ratio (DNR) for the 2ChDPs and 2CEOAEs. The DNR is typically 20-30 dB.
      An intermittent noise rejection technique is implemented in real time that
      compares a currently acquired ear-canal response with a stored response.
      Dissimilar responses indicate the presence of intermittent noise, and the noise
      contaminated responses are thereby discarded before ensemble averaging.

PMID- 9637035
TI  - Dichotic pitches as illusions of binaural unmasking. I. Huggins' pitch and the
      "binaural edge pitch".
AB  - The two most salient dichotic pitches, the Huggins pitch (HP) and the binaural
      edge pitch (BEP), are produced by applying interaural phase transitions of 360
      and 180 degrees, respectively, to a broadband noise. This paper examines accounts
      of these pitches, concentrating on a "central activity pattern" (CAP) model and a
      "modified equalization-cancellation" (mE-C) model. The CAP model proposes that a
      dichotic pitch is heard at frequency f when an individual across-frequency scan
      in an interaural cross-correlation matrix contains a sharp peak at f. The mE-C
      model proposes that a dichotic pitch is heard when a plot of interaural
      decorrelation against frequency contains a peak at f. The predictions of the
      models diverge for the BEP at very narrow transition bandwidths: the mE-C model
      predicts that salience is sustained, while the CAP model predicts that salience
      declines and that the dominant percept is of the in-phase segment of the noise.
      Experiment 1 showed that the salience of the BEP was sustained at the narrowest
      bandwidths that could be generated (0.5% of the transition frequency). Experiment
      2 confirmed that the pitch of a BEP produced by a 0.5% transition bandwidth was
      close to the frequency of the transition band. Experiment 3 showed that pairs of
      simultaneous narrow 180-degree transitions, whose frequencies corresponded to
      vowel formants, were perceived as the intended vowels. Moreover, the same vowels
      were perceived whether the in-phase portion of the noise lay between the two
      transition frequencies or on either side of them. In contrast, different patterns
      of identification responses were made to diotic band-pass and band-stop noises
      whose cutoff frequencies corresponded to the same formants. Thus, the vowel
      identification responses made to the dichotic stimuli were not based on hearing
      the in-phase portions of the noise as formants. These results are not predicted
      by the CAP model but are consistent with the mE-C model. It is argued that the mE
      C model provides a more coherent and parsimonious account of many aspects of the
      HP and the BEP than do alternative models.

PMID- 9637036
TI  - Dichotic pitches as illusions of binaural unmasking. II. The Fourcin pitch and
      the dichotic repetition pitch.
AB  - The predictions of three models are compared with respect to existing
      experimental data on the perception of the Fourcin pitch (FP) and the dichotic
      repetition pitch (DRP). Each model generates a central spectrum (CS), which is
      examined for peaks at frequencies consistent with the perceived pitches. A
      modified equalization-cancellation (mE-C) model of binaural unmasking [Culling
      and Summerfield, J. Acoust. Soc. Am. 98, 785-797 (1995)] generates a CS which
      reflects the degree of interaural decorrelation present in each frequency
      channel. This model accounts for the perceived frequencies of FPs, but produces
      no output for DRP stimuli. A restricted equalization-cancellation (rE-C) model
      [Bilsen and Goldstein, J. Acoust. Soc. Am. 55, 292-296 (1974)] sums the time
      varying excitation in corresponding frequency channels, without equalization, to
      form a CS. A central activity pattern (CAP) model [Raatgever and Bilsen, J.
      Acoust. Soc. Am. 80, 429-441 (1986)] generates a CS by scanning an interaural
      cross-correlation matrix across frequency. The rE-C and CAP models yield
      inaccurate predictions of the perceived frequencies of FPs, but predict the
      occurrence of the DRP and its correct pitch. The complementary predictions of the
      mE-C model compared to the rE-C and CAP models, together with the evidence that
      the FP is clearly audible for the majority of listeners, while the DRP is faintly
      heard by a minority of listeners, suggest that the mE-C model provides the best
      available account of the FP, and that the DRP is produced by a separate
      mechanism.

PMID- 9637037
TI  - Evidence for an across-frequency, between-channel process in asymptotic monaural
      temporal gap detection.
AB  - Monaurally measured temporal gap detection (TGD) thresholds characteristically
      increase as the frequency difference is increased over a range of about half an
      octave to an octave between two sinusoids that mark the onset and offset of the
      silent gap. For greater sinusoidal frequency separations, the TGD thresholds
      often become asymptotic. This pattern probably reflects two different processes.
      The first process likely reflects within-channel processing within a single
      auditory filter or channel. The second process is less certain, but may reflect
      between-channel processing of the silent gap stimulus across two or more
      independent frequency channels. To evaluate the hypothesis that asymptotic
      monaural gap detection can be explained by a simple between-channel process, TGD
      thresholds were measured as a function of frequency separation between a pregap
      sinusoid presented to the left ear (channel 1) and a postgap sinusoid, of higher
      frequency, presented to the right ear (channel 2). The rationale for dichotic
      presentation of the sinusoidal markers and gap signal followed from the fact that
      the gap detection task must be performed between two independent channels by
      combining the outputs from each channel (ear) and recovering the gap information
      centrally. The resulting TGD thresholds for pregap sinusoids from 250 to 4000 Hz
      were relatively invariant and increased only slightly with increasing marker
      frequency separation. The average TGD thresholds for four listeners were in the
      range of 30 to 40 ms, which corresponded closely with their asymptotic TGD
      thresholds for the same set of stimulus conditions measured monaurally. This
      correspondence of the two data sets supports an across-frequency, between-channel
      process for asymptotic monaural gap detection at marker frequency separations
      greater than about half an octave.

PMID- 9637038
TI  - The role of auditory filters in comodulation masking release (CMR).
AB  - Comodulation masking release (CMR) is the detection advantage conferred by
      coherence of amplitude modulation across masker frequency. This phenomenon has
      typically been described in terms of across-frequency comparisons or in terms of
      cueing, where analysis of the output of an auditory filter in the region of the
      signal is aided by the outputs of independent auditory filters. An alternative
      approach is to assume a broad initial predetection filter, one which encompasses
      frequencies generally thought to fall into disparate auditory filters. These two
      basic approaches are compared. Stimuli consisted of comodulated maskers, spaced
      in frequency at one of three fixed intervals, with fine structure that either
      produced strong envelope beats in the summed waveform or did not. The signal was
      a pure tone of random starting phase. For the smallest masker frequency spacing
      detection of a high-frequency signal seemed to be improved in the presence of
      envelope beats, while detection of a low-frequency signal seemed to be degraded
      by envelope beats. These results are discussed in terms of the number of maskers
      assumed to sum in an auditory filter and the relative availability of within- and
      between-channel cues. This explanation is consistent with an initial stage of
      auditory filtering and is fundamentally inconsistent with a broad initial filter.
      Results for larger masker frequency spacings showed this trend less reliably, a
      finding that was further explored via data from a modulation discrimination task.

PMID- 9637039
TI  - Auditory perception following hair cell regeneration in European starling
      (Sturnus vulgaris): frequency and temporal resolution.
AB  - Behavioral detection thresholds, auditory filter widths, and temporal modulation
      transfer functions were obtained from four starlings before, during and after 11
      days of subcutaneous injections of kanamycin, an aminoglycoside antibiotic. Birds
      were operantly conditioned to respond to pure tones and amplitude modulated
      noises ranging in frequency from 0.25 to 7 kHz using adaptive staircase
      procedures and were tested daily for 92 days after the first injection of
      aminoglycoside. All birds had threshold shifts of at least -60 dB at frequencies
      above 4 kHz. Lower frequencies were affected in some birds, although none of the
      birds had hearing loss below 3 kHz. All four birds had wider auditory filters at
      5 kHz immediately after the aminoglycoside series. Any changes in frequency
      resolution at frequencies below 5 kHz were slight, transitory, and rarely
      observed. Two of the four birds had permanently wider auditory filters at 5 kHz.
      Temporal modulation transfer functions were briefly affected in two birds during
      the time of greatest threshold shift. Recovery of detection thresholds began soon
      after the injections ceased and continued for approximately 60 days. Recovery in
      frequency resolution lagged behind auditory threshold by about 10 days. Normal
      temporal resolution was observed in the context of impaired intensity and
      frequency resolution. Changes in auditory threshold and frequency resolution were
      closely associated for all birds at 5 kHz, but were correlated with statistical
      significance in only two birds. Scanning electron microscopy was performed on all
      four birds after 90 days of recovery and confirmed that the extent of initial
      damage was consistent with the pattern of observed hearing loss.

PMID- 9637040
TI  - Auditory scene analysis by European starlings (Sturnus vulgaris): perceptual
      segregation of tone sequences.
AB  - Like humans, animals that use acoustic stimuli to perceive their world ought to
      be able to parse the auditory scene into functionally significant sounds. The
      ability to do so ought to have significant adaptive value when, for example, an
      animal can identify the sounds of a predator among other natural noises. In
      earlier work it was shown that a species of songbird, the European starling, can
      identify excerpts of both its own song and songs from other avian species when
      the songs are mixed concurrently with other natural signals. In this experiment
      it is demonstrated that starlings can segregate two synthetic pure-tone sequences
      when the sequences differ in frequency. Taken together, the experiments show that
      at least one nonhuman species is capable of auditory scene analysis both for
      natural and for non-natural acoustic stimuli. This suggests in turn that auditory
      scene analysis may be a general perceptual process that occurs in many species
      that make use of acoustic information.

PMID- 9637041
TI  - Effects of spectral pattern on the perceptual salience of partials in harmonic
      and frequency-shifted complex tones: a performance measure.
AB  - A single even harmonic added to an odd-harmonic complex is often judged to be
      more salient than its odd neighbors in a clarity rating task [Roberts and
      Bregman, J. Acoust. Soc. Am. 90, 3050-3060 (1991)]. This study used similar
      complexes in a two-interval forced-choice procedure. Each interval consisted of a
      complex tone followed by a pure tone, whose frequency matched that of a harmonic
      in one interval but was changed by +/- 0.5 x fundamental frequency in the other.
      Subjects were asked to identify the matching interval. Since the pure tone
      followed the complex tone, it could not cue listening to a particular frequency
      region. The possibility of cross-interval cuing was reduced by changing the
      fundamental frequency between intervals (100-150 Hz range). The procedure was
      designed to maximize the effects on performance of differences in immediate
      perceptual salience between the partials. The added even harmonic was typically
      judged with greater accuracy than its odd neighbors (experiment 1), though this
      effect was greatly reduced for harmonics above 8 (experiment 2). The even-odd
      difference persisted when the original stimuli were made inharmonic by applying a
      frequency shift of 15%, but was abolished for stimuli consisting of successive
      partials (experiment 3).

PMID- 9637042
TI  - Adaptation in the processing of interaural time differences revealed by the
      auditory localization aftereffect.
AB  - Two experiments were conducted involving the auditory localization aftereffect,
      in which the perceptual lateralization of a test sound having an interaural time
      difference (ITD) shifts away from that of a prior adapting sound having a
      different ITD. First, the frequency selectivity of the aftereffect was examined
      for sinusoids presented through headphones, with various combinations of adapter
      and test frequencies below 800 Hz, using the method of constant stimuli. The
      magnitude of the aftereffect was found to be largest when the frequencies of the
      two tones were similar, and virtually disappeared at a frequency difference of
      one-half octave. Second, the ITD selectivity of the aftereffect was examined for
      400-Hz sinusoids. Subjects' judgments of lateralization were measured directly in
      terms of the perceived azimuth of the test tone for various combinations of
      adapter and test ITDs in the range of +/- 625 microseconds. The magnitude of the
      aftereffect was found to be largest when adapter and test ITDs differed by
      approximately 250 microseconds. These results were successfully simulated by an
      interaural cross-correlation model having gain control. The results are
      consistent with the idea that the gain of ITD-selective units, located after
      binaural interaction but before across-frequency integration, is changed by
      recent input.

PMID- 9637043
TI  - An adaptive noise canceller for hearing aids using two nearby microphones.
AB  - An adaptive noise cancellation scheme based on two-stage adaptive filtering as
      proposed by Van Compernolle [Proceedings of the IEEE International Conference on
      Acoustics, Speech and Signal Processing (IEEE, New York, 1990)] was tested for
      two identical directional microphones mounted in an endfire configuration within
      a single behind-the-ear (BTE) hearing aid. Speech intelligibility tests were
      carried out with two normal hearing subjects and three hearing aid users with
      moderate hearing losses, in a realistic test environment using open set words and
      sentences. A significant improvement, on average more than 5 dB, of speech
      reception threshold (SRT) in background noise was obtained.

PMID- 9637044
TI  - Deformation analysis of the vocal folds from videostroboscopic image sequences of
      the larynx.
AB  - Videostroboscopy is an examination which yields a permanent record of the moving
      vocal folds. Thus, it allows the diagnosis of abnormalities which contribute to
      voice disorders. In this paper, in order to find and quantify the deformation of
      the vocal folds in videostroboscopic recordings, an active contours- (snakes)
      based approach is used to delineate the vocal folds in each frame of the
      videostroboscopic image sequence. After this delineation, a new elastic
      registration algorithm is used to register the vocal fold contours between
      adjacent frames of the video sequence. This algorithm is based on the
      regularization principle and is very effective when large deformations are
      present. A least-squares approach is used to fit an affine model to the
      displacement vectors found by elastic registration. The parameters of this model,
      rotation, translation, and deformation along two principle axes, quantify the
      deformation and allow the succinct characterization of the videostroboscopic
      recordings based on the deformations that occurred. Experiments are shown with
      synthetic and real videostroboscopic data that demonstrate the value of the
      proposed approach.

PMID- 9637045
TI  - Fundamental frequency during phonetically governed devoicing in normal young and
      aged speakers.
AB  - Age-related changes in the laryngeal system can be perceived as altered vocal
      pitch and increased pitch variability. However, reports vary as to the nature and
      extent of an age effect on fundamental frequency (F0) for analyses taken over
      long segments of connected speech. Analysis of F0 across a smaller time frame may
      be more informative. Young speakers show an increase in F0 associated with
      phonetically governed devoicing gestures that is likely mediated by increased
      vocal fold stiffness. Anatomic and neurophysiologic changes in the aged larynx
      may limit the role of increased vocal fold stiffness in the devoicing gesture.
      This study tests the hypothesis that aged speakers show a smaller increase in F0
      in association with the devoicing gesture for production of an intervocalic
      voiceless obstruent than do young speakers. Normal young and aged speakers
      produced a short sentence containing an intervocalic voiceless obstruent.
      Measures of F0 were obtained for ten cycles before voice offset and ten cycles
      after voice onset. Young speakers showed a small increase in F0 during devoicing
      whereas aged speakers showed a decrease in F0 during devoicing. Aged speakers
      seem to rely more on vocal fold abduction rather than a combination of abduction
      and tensing to achieve devoicing.

PMID- 9637046
TI  - Depolarizing the perceptual magnet effect.
AB  - In recent years there has been a great deal of interest in demonstrations of the
      so-called "Perceptual-Magnet Effect" (PME). In these studies, AX-discrimination
      tasks purportedly reveal that discriminability of speech sounds from a single
      category varies with judged phonetic "goodness" of the sounds. However, one
      possible confound is that category membership is determined by identification of
      sounds in isolation, whereas, discrimination tasks include pairs of stimuli. In
      the first experiment of the current study, identification and goodness judgments
      were obtained for vowels (/i/-/e/) presented in pairs. A substantial shift in
      phonetic identity was evidenced with changes in the context vowel. In a second
      experiment, listeners participated in an AX-discrimination task with the vowel
      pairs from the first experiment. Using the contextual identification functions
      from the first experiment, predictions of discriminability were calculated using
      the classic tenets of Categorical Perception. Obtained discriminability functions
      were well accounted for by predictions from identification. There was no
      additional unexplained variance that required the proposal of "perceptual
      magnets." These results suggest that PME may be nothing more than further
      demonstration that general discriminability is greater for cross-category
      stimulus pairs than for within-category pairs.

PMID- 9637047
TI  - Adapting to supernormal auditory localization cues. I. Bias and resolution.
AB  - Head-related transfer functions (HRTFs) were used to create spatialized stimuli
      for presentation through earphones. Subjects performed forced-choice,
      identification tests during which allowed response directions were indicated
      visually. In each experimental session, subjects were first presented with
      auditory stimuli in which the stimulus HRTFs corresponded to the allowed response
      directions. The correspondence between the HRTFs used to generate the stimuli and
      the directions was then changed so that response directions no longer
      corresponded to the HRTFs in the natural way. Feedback was used to train subjects
      as to which spatial cues corresponded to which of the allowed responses. Finally,
      the normal correspondence between direction and HRTFs was reinstated. This basic
      experimental paradigm was used to explore the effects of the type of feedback
      provided, the complexity of the stimulated acoustic scene, the number of allowed
      response positions, and the magnitude of the HRTF transformation subjects had to
      learn. Data showed that (1) although subjects may not adapt completely to a new
      relationship between physical stimuli and direction, response bias decreases
      substantially with training, and (2) the ability to resolve different HRTFs
      depends both on the stimuli presented and on the state of adaptation of the
      subject.

PMID- 9637048
TI  - Adapting to supernormal auditory localization cues. II. Constraints on adaptation
      of mean response.
AB  - A series of experiments was performed in which subjects were trained to interpret
      auditory localization cues arising from locations different from their normal
      spatial positions. The exact pattern of mean response to these alterations (as a
      function of time) was examined in order to begin to develop a quantitative model
      of adaptation. Mean responses were roughly proportional to the normal position
      associated with the localization cues presented. As subjects adapted, the best
      fit slope (relating mean response and normal position) changed roughly
      exponentially with time. The exponential rate and adaptation asymptote were found
      for each subject in each experiment, as well as the rate and asymptote of
      readaptation to normal cues. The rate of adaptation does not show any statistical
      dependence on experimental conditions; however, the asymptote of the best-fit
      slope varied with the strength of the transformation used in each experiment.
      This result is consistent with the hypothesis that subjects cannot adapt to a
      nonlinear transformation of auditory localization cues, but instead adapt to a
      linear approximation of the transformation. Over time, performance changes
      exponentially towards the best-fit linear approximation for the transformation
      used in a particular experiment, and the rate of this adaptation does not depend
      upon the transformation employed.

PMID- 9637049
TI  - Complementarity and synergy in bimodal speech: auditory, visual, and audio-visual
      identification of French oral vowels in noise.
AB  - The efficacy of audio-visual interactions in speech perception comes from two
      kinds of factors. First, at the information level, there is some
      "complementarity" of audition and vision: It seems that some speech features,
      mainly concerned with manner of articulation, are best transmitted by the audio
      channel, while some other features, mostly describing place of articulation, are
      best transmitted by the video channel. Second, at the information processing
      level, there is some "synergy" between audition and vision: The audio-visual
      global identification scores in a number of different tasks involving acoustic
      noise are generally greater than both the auditory-alone and the visual-alone
      scores. However, these two properties have been generally demonstrated until now
      in rather global terms. In the present work, audio-visual interactions at the
      feature level are studied for French oral vowels which contrast three series,
      namely front unrounded, front rounded, and back rounded vowels. A set of
      experiments on the auditory, visual, and audio-visual identification of vowels
      embedded in various amounts of noise demonstrate that complementarity and synergy
      in bimodal speech appear to hold for a bundle of individual phonetic features
      describing place contrasts in oral vowels. At the information level
      (complementarity), in the audio channel the height feature is the most robust,
      backness the second most robust one, and rounding the least, while in the video
      channel rounding is better than height, and backness is almost invisible. At the
      information processing (synergy) level, transmitted information scores show that
      all individual features are better transmitted with the ear and the eye together
      than with each sensor individually.

PMID- 9637050
TI  - Sinuous instability of a planar air jet: propagation parameters and acoustic
      excitation.
AB  - The sinuous instability wave of a planar air jet is excited by localized acoustic
      flow across the nozzle. Phase velocity and the growth exponent are found from
      synchronous hot-wire measurements made beyond the excited region, where the
      profile is approximately sech-squared. In the observed range of scaled radian
      frequency, 0.02-1.33 (the stability limit), results agree with real-frequency
      (spatially growing) analysis but not with complex-frequency (temporally growing)
      analysis. The latter predicts smaller phase velocity at low frequencies and has
      been questioned in edgetone analysis. In further tests, the acoustic driving
      signal is made independent of downstream distance, as in an organ pipe. The jet
      deflection is then the sum of acoustic convection and of the instability wave,
      summing to zero at the nozzle, as proposed by Fletcher, Elder, and others. The
      instability-wave theory applies to linear behavior in the inviscid limit and
      therefore to a hypothetical nonspreading jet. The local velocity profile width
      must be considered in relating to a physical jet. In a flue organ pipe
      oscillating at equilibrium amplitude the stability-wave theory is not applicable
      near the lip, where the laminar flow assumed in the theory disappears and the jet
      deflection exceeds the range of linear behavior. Direct sound generation by the
      jet is investigated briefly.

PMID- 9637051
TI  - Variables controlling contrast generation in a urinary bladder model.
AB  - An ultrasound system has been developed to generate microbubbles in vivo for use
      as ultrasound contrast agent. Possible application include diagnosis of reflux in
      the urinary tract. In experiments designed to elucidate the contrast microbubble
      generation process, acoustic bursts (at 1.8 MHz, 125 ms) were propagated through
      a latex rubber balloon, modeled after a rabbit urinary bladder, containing fluids
      of various air and carbon dioxide saturations and concentrations of cavitation
      nuclei (0.198-micron-diam polystyrene particles). The peak rarefactional pressure
      threshold for contrast microbubble generation, as visualized with a diagnostic
      ultrasound system, decreased approximately a factor of 2 for increasing particle
      concentration from 10(8) to 10(10) particles/cc, with the lowest threshold of
      5.24 MPa. For samples with gas saturations below 50% and 10(10) particles/cc, the
      average thresholds were at least twice as high as those of more saturated fluids
      (with mean threshold for saturated fluids of 6.45 MPa), and samples containing
      CO2 had considerably lower thresholds than respective under-saturations in air.
      At a fixed pressure amplitude, echogenicity tended to increase with both
      increasing particle concentration and gas saturation; this was more favorable for
      samples containing CO2. Even in a restricted-nuclei environment such as the
      urinary bladder, generation of vaporous cavitation should be possible; however,
      subsequently, abundant gas is needed to grow vaporous bubbles to persistent and
      imageable sizes, to assist in the diagnosis of urinary reflux.

PMID- 9637052
TI  - A method for forward and inverse solutions of a three-dimensional model of the
      cochlea.

PMID- 9637053
TI  - Auditory saltation: a new measure for an old illusion.

PMID- 9637054
TI  - Effect of climate upon organ tone.

PMID- 9637055
TI  - Evolution of segregation distortion: potential for a high degree of polymorphism.
AB  - By means of a population genetical model, we study the evolution of segregation
      distortion. Most models of segregation distortion focus on a single distorter
      allele. In contrast, we consider the competition between a large number of
      distorters. Motivated by systems as the t complex of the house mouse or the Sd
      complex of Drosophila melanogaster, we assume that there is some
      "complementation" between distorter alleles, i.e. that the fitness of individuals
      heterozygous for two distorter alleles is higher than the fitness of homozygous
      individuals. In the presence of complementation, the most efficient distorter
      allele with the highest segregation ratio often does not outcompete less
      efficient distorters. In fact, our results show that coexistence of a large
      number of distorter alleles is more typical than the competitive exclusion of
      less efficient distorters by a single superior allele. We first consider the
      analytically tractable system where all distorters show the same amount of
      complementation. In this case, all distorters with a segregation ratio higher
      than a certain critical value will persist, resulting in a polymorphic population
      where the average segregation ratio is only slightly larger than 0.5. If the
      degree of complementation varies, there may be more than one stable equilibrium,
      and the outcome of competition may depend on the initial conditions. Motivated by
      empirical examples, we also consider the case that the distorting ability of an
      allele is negatively related to its effects on individual fitness. Interestingly,
      the outcome of competition depends crucially on details of such a trade-off. We
      conclude that verbal arguments are insufficient to predict the evolution of
      segregation distortion.

PMID- 9637056
TI  - Cyclical neutropenia and the peripheral control of white blood cell production.
AB  - Cyclical neutropenia (CN) is an interesting dynamic hematological disease in
      which the neutrophils spontaneously oscillate from approximately normal levels to
      near zero with a period between 19 and 21 days. In the only known animal model
      for this disorder, the grey collie, the disease's single apparent difference from
      human CN is the smaller period of 11-15 days. CN can be treated using the
      cytokine G-CSF which decreases the period (to about 14 days in humans), increases
      the mean value, and elevates the amplitude of the oscillations. After reviewing
      the clinical and laboratory data on this disease, we examine the proposition that
      CN is due to a loss of stability in the peripheral negative feedback control of
      neutrophil production. This is accomplished by the development of a
      physiologically realist mathematical model for the system. We conclude that there
      is no consistent way in which such a destabilization can give rise to either the
      clinical or laboratory characteristics of CN. Rather it seems more likely that
      the oscillations of CN are generated within the pluripotential stem cell
      population.

PMID- 9637057
TI  - Evaluation of residual stress in rabbit skin and the relevant material constants.
AB  - Material constants are needed in order to evaluate stresses. The material
      constants for orthotropic rabbit skin when residual stresses are eliminated, have
      been evaluated by Tong & Fung [(1976). J. Biomechanics 9, 649-657]. It is well
      documented that a circular skin sample taken from the human body becomes
      elliptical in shape. Thus, it is clear that there are residual stresses in human
      skin which need to be taken into consideration when evaluating the material
      constants. In this paper, we therefore evaluate the material constants for rabbit
      skin taking into account residual stresses.

PMID- 9637059
TI  - A PRC based model of a pacemaker cell: effect of vagal activity and investigation
      of the respiratory sinus arrhythmia.
AB  - In this study we present a computer model of a pacemaker cell subjected to vagal
      stimulation. This model allows us to investigate the entrainment phenomena of the
      pacemaker cell resulting from its dynamic interaction with a periodic train of
      vagal bursts. The possibility of entrainment depends mainly on the fact that a
      vagal stimulation discharge can "correct" the pacemaker rhythm by an amount that
      depends on its instantaneous relationship to the pacemaker cycle length. This
      very simple model, is based on the two most important functional properties of
      the cardiac pacemaker cells. The first property is the intrinsic pacemaker cycle
      length, which is an "internal" parameter of the cell, describing the most basic
      feature of a pacemaker cell. The second one is the phase response curve (PRC),
      which is an "overall collective" function, containing all the "information" about
      the possible interactions between the pacemaker cell and the outside world (i.e.
      its interaction with surrounding cells, external stimulus, etc.). A "collective"
      PRC was reconstructed from the resulting effects of all the pulses composing a
      burst. It appears that the PRC parameters as well as the vagal burst parameters
      are important factors in predicting the entrainment phenomena. Specifically, we
      found that the tendency of the pacemaker cell to become synchronized with bursts
      of vagal activity is greater, the larger the number of pulses per burst. However,
      increasing the number of pulses may also increase the tendency of the pacemaker
      towards instability, which was unveiled as changes in the configuration of the
      "collective" PRC. We applied the periodic train of vagal bursts so as to simulate
      the respiratory sinus arrhythmia (RSA) modulation on the pacemaker cell. We
      included also a modulation of sympathetic origin, represented as periodic changes
      in the intrinsic pacemaker cycle length. The frequency response of the pacemaker
      to "autonomic" modulations allowed us to demonstrate that the RSA dynamics can be
      interpreted in terms of the entrainment of the pacemaker cell by the respiratory
      modulation of vagal activity.

PMID- 9637060
TI  - Topographic mapping in the retinotectal projection by means of complementary
      ligand and receptor gradients: a computer simulation study.
AB  - Based on recent experimental studies of complementary gradients of receptor
      density (R) on the retinal surface and ligand density (L) on the tectal surface,
      and mapping of the high point on the receptor gradient to the low point on the
      ligand and vice versa, the servomechanism model was constructed involving a
      mechanism for the retinal axon to reach its target automatically sensing a
      difference between the signal strength (R.L) and the standard value (S). Computer
      simulations based on the model demonstrated desired two-dimensional topographic
      mapping of the retinal axons on the tectum, and explained three strange behaviors
      of the retinal axons that had been observed in stripe assays for retinal axons
      using stripes composed of tectal membrane fragments: repulsive behaviors of the
      retinal axons by the ligand substances, uncertainty of the nasal axons whether or
      not they show regional selectivity between substances of anterior and posterior
      tecta, and abrupt transition of growth of the axons originating at continuously
      varied retinal positions on the stripes having graded ligand density. Finally we
      suggested what is to be improved in stripe assays with the artificial gradient of
      the tectal membrane fragments.

PMID- 9637061
TI  - Pepsin inhibitor from roots of Anchusa strigosa.
AB  - A pepsin inhibitor of undetermined exact chemical composition was isolated from
      the aqueous extracts of the roots of Anchusa strigosa. The extract of 1 g dry
      roots inhibited 9380 +/- 390 micrograms of pepsin. The main steps of the
      isolation procedure consisted of extraction in boiling water, precipitation at pH
      3 and washing the precipitate with ethanol, column chromatography on sephadex G
      75, and finally ultrafiltration on UM10 membrane. The specific activity at the
      last step was 44 units ml-1 solution which measured 1.0 at 287 nm (a one unit of
      the inhibitor is that amount which inhibited 1 microgram of pepsin under the
      conditions of the assay). The overall purification was 22-fold. The inhibitor did
      not bind CM-cellulose, but it did bind DEAE-cellulose irreversibly. A pepsin
      inhibitor complex was formed with a KI = 2 x 10(-8) M. The inhibitor inhibited
      peptic milk-clotting activity at pH 5.3. A solution of the inhibitor exhibited
      split-peak spectra with two maxima at 280 nm and 287 nm. The epsilon at 287 nm
      was estimated at 9.4 x 10(5) l mol-1 cm-1 based on a M(r) value which was
      estimated at 62,500.

PMID- 9637062
TI  - Inhibition of O2-reducing activity of horseradish peroxidase by
      diphenyleneiodonium.
AB  - Plant cells respond to pathogen attach with a burst of H2O2 secretion. The
      question whether this defense reaction is catalysed by a NAD(P)H oxidase similar
      to the NADPH oxidase of phagocytic leukocytes in mammals or by an extracellular
      peroxidase is presently a matter of controversial debate. The observation that
      H2O2 production by plant cells can be inhibited by diphenyleneiodonium (DPI), a
      potent inhibitor of the mammalian NADPH oxidase, has fostered the view that a
      mammalian-type enzyme is responsible for the H2O2 production by plant cells. Here
      we show that DPI inhibits the NADH-dependent H2O2 production by horseradish
      peroxidase in the same concentration range as previously used for the inhibition
      of putative NADPH oxidase activity in plants. The peroxidative activity normally
      used for assaying peroxidase is not affected by DPI, indicating that the
      inhibitor specifically interferes with a partial reaction that is exclusively
      involved in the O2 reducing activity of the enzyme.

PMID- 9637063
TI  - Multiple forms of polygalacturonase from banana fruits.
AB  - Three multiple forms of polygalacturonase (PG) in ripe and two in unripe banana
      (Musa acuminata) fruits were separated by DEAE-cellulose and further purified
      using Sephadex G-150 chromatography. The multiple forms can be differentiated
      from each other on the basis of their properties. PG1 and PG3 were identified as
      endo-PG and PG2 as exo-PG on the basis of decrease in viscosity, increase in
      reducing sugar and the reaction product. PG2 and PG3 increased with the ripening
      of fruits. PG1, PG2 and PG3 exhibited optimum activity at pH 3.3, 3.7 and 4.3,
      respectively. Complete loss of PG2 and PG1 activities occurred at 60 and 70
      degrees, but PG3 retained 60 and 50% activity respectively. The three forms
      showed a different response towards divalent metal ions. Ca2+ activated PG1
      activity only. Teepol 0.1%, inhibited PG1 activity by 25%, but PG2 and PG3
      activities were completely inhibited. CTAB, 0.1%, had no effect on PG1 and PG2
      activities, but inhibited PG3 activity by 40%. 2-ME stimulated PG2 and PG3
      activities but had no effect on PG1 activity. Gel filtration through Sephacryl
      indicated M(r) of 23,200, 58,000 and 130,000, respectively, for PG1, PG2 and PG3.
      The substrate saturation curve for PG1 and PG2 were Michaelian, while PG3 showed
      biphasic curve. The Km values of PG1 and PG2 were 0.22% and 0.14%, respectively.

PMID- 9637064
TI  - Anthocyanin production of Glehnia littoralis callus cultures.
AB  - A stable callus line that produces anthocyanins was established from callus
      derived from a petiole of a Glehnia littoralis seedling and subcultured in the
      dark. The major anthocyanin which made up about 60% of the total anthocyanins was
      determined as cyanidin 3-O-(6-O-(6-O-(E)-feruloyl-beta-D-glucopyranosyl) -2-O
      beta-D-xylopyranosyl-beta-D-glucopyranoside) by chemical and spectroscopic
      analyses. Anthocyanin contents in the cells cultured on B5 basal medium
      containing NAA (1 mg l-1), kinetin (0.01 mg l-1) and 3% sucrose reached 14% (dry
      wt basis) and the productivity has been sustained for 5 years.

PMID- 9637065
TI  - Sasanquol, a 3,4-seco-triterpene alcohol from sasanqua oil, and its anti
      inflammatory effect.
AB  - A novel 3,4-seco-triterpene alcohol, named sasanquol, was isolated from the non
      saponifiable lipid of sasanqua oil from the seeds of Camellia sasanqua. Its
      structure was established to be 3,4-seco-D:B-friedobacchara-4,21-dien-3-ol by
      spectroscopic methods. This is the first example of naturally occurring
      triterpene with a D:B-friedobaccharane skeleton. The 50% inhibitory dose of this
      compound against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear
      inflammation (1 microgram per ear) in mice was 0.4 mg per ear.

PMID- 9637066
TI  - Phenylpropanoids and flavonoid glycosides from Lysionotus pauciflorus.
AB  - A new phenylpropanoid glycoside, alpha-(3,4-dihydroxyphenyl)ethyl-(2'-O-alpha-L
      rhamno-pyranosyl- 3'-O-beta-D-apiofuranosyl-4'-O-E-caffeoyl)-beta-D-glucopyran
      oside, verbascoside, and two new flavone glucosides, nevadensin 7-O-beta-D
      glucoside and nevadensin 7-O-[alpha-L-rhamnosyl(1-->6)]-beta-D-glucoside, have
      been isolated from the aerial parts of Lysionotus pauciflorus. The structures
      have been elucidated on the basis of spectroscopic data and chemical correlation.

PMID- 9637067
TI  - An isopavine alkaloid from Thalictrum minus.
AB  - A new alkaloid, isothalisopavine, was isolated from Thalictrum minus and shown to
      be 2,3,8-trimethoxy-7-hydroxyisopavine from spectral evidence. The known
      thalisopavine, from T. dasycarpum, is 2,3,8-trimethoxy-9-hydroxyisopavine.
      Isothalisopavine is the first of its class to be substituted unsymmetrically in
      the two aromatic rings.

PMID- 9637068
TI  - Three-dimensional analysis of the senescence program in rice (Oryza sativa L.)
      coleoptiles. Investigations of tissues and cells by fluorescence microscopy.
AB  - The coleoptile of rice (Oryza sativa L. cv. Nippon-bare) emerges from an imbibed
      seed on day 2 after sowing. Then, it matures and senesces rapidly. For analysis
      of the senescence pattern within individual coleoptiles, we monitored the
      distribution of chlorophyll (Chl) in entire coleoptiles and in cross-sections of
      coleoptiles by recording the autofluorescence of Chl. Degradation of Chl was
      apparent at the tip of the margins of opened-out coleoptiles on day 4, when the
      overall levels of soluble protein and Chl per coleoptile had reached maximum
      values. Then, senescence proceeded from the tip to the base and from the inner
      mesophyll cells towards the outer epidermis, excluding tissues along vascular
      bundles. Further analysis of cellular senescence using samples embedded in
      Technovit 7100 resin revealed that the senescence of each green mesophyll cell
      followed an identical program, which consisted of the following steps: (i)
      degradation of chloroplast DNA; (ii) condensation of the nucleus, decrease in the
      size of chloroplasts, degradation of ribulose-1,5-bisphosphate
      carboxylase/oxygenase and chloroplast inner membranes; (iii) disorganization of
      the nucleus; (iv) complete loss of cellular components, distortion of the cell
      wall. Although the timing of each step and the rate at which each step was
      completed differed among cells of different locations within the coleoptile, this
      sequence was observed in all mesophyll cells in the coleoptile.

PMID- 9637069
TI  - The promoter of a gene encoding a polygalacturonase-inhibiting protein of
      Phaseolus vulgaris L. is activated by wounding but not by elicitors or pathogen
      infection.
AB  - Polygalacturonase-inhibiting proteins (PGIPs), leucine-rich repeat (LRR) proteins
      evolutionarily related to several plant resistance genes, bind to and regulate
      the action of fungal endopolygalacturonases. In Phaseolus vulgaris L., PGIPs are
      encoded by a gene family comprising at least five members. As a start for a
      systematic analysis of the regulation of the pgip family, we have analysed the
      ability of the promoter of the bean gene pgip-1 to direct expression of beta
      glucuronidase (GUS) in transfected tobacco protoplasts, microbombarded bean and
      tobacco leaves, and transgenic tobacco plants. In protoplasts, the pgip-1 gene
      region from nucleotide (nt) -2004 to nt +27 directed a level of expression that
      was as high as that directed by the cauliflower mosaic virus (CaMV) 35S promoter
      and could not be further induced by elicitor treatment; alteration of the region
      immediately following the TATAA sequence at nt -29 abolished expression. Upon
      stable integration into tobacco plants of the pgip-1 promoter-GUS construct, as
      well as of a -394 deletion, expression was detected for both constructs mainly in
      the stigma and, to a lesser extent, in the anthers and in the conductive vascular
      tissue. The promoter responded to wounding but not to oligogalacturonides, fungal
      glucan, salicylic acid, cryptogein, or pathogen infection. This expression
      pattern does not mirror that of the whole pgip gene family.

PMID- 9637070
TI  - Uptake and translocation of phosphate by pho2 mutant and wild-type seedlings of
      Arabidopsis thaliana.
AB  - The pho2 mutant of Arabidopsis thaliana (L.) Heynh. accumulates excessive Pi
      (inorganic phosphate) concentrations in shoots compared to wild-type plants (E.
      Delhaize and P. Randall, 1995, Plant Physiol. 107: 207-213). In this study, a
      series of experiments was conducted to compare the uptake and translocation of Pi
      by pho2 with that of wild-type plants. The pho2 mutants had about a twofold
      greater Pi uptake rate than wild-type plants under P-sufficient conditions and a
      greater proportion of the Pi taken up accumulated in shoots of pho2. When shoots
      were removed, the uptake rate by roots was found to be similar for both
      genotypes, suggesting that the greater Pi uptake by the intact pho2 mutant is due
      to a greater shoot sink for Pi. Although pho2 mutants could recycle 32Pi from
      shoots to roots through phloem the proportion of 32Pi translocated to roots was
      less than half of that found in wild-type plants. When transferred from P
      sufficient to P-deficient solutions, Pi concentrations in pho2 roots had a
      similar depletion rate to wild-type roots despite pho2 shoots having a fourfold
      greater Pi concentration than wild-type shoots throughout the experiment. We
      suggest that the pho2 phenotype could result from a partial defect in Pi
      transport in the phloem between shoots and roots or from an inability of shoot
      cells to regulate internal Pi concentrations.

PMID- 9637071
TI  - The role of acyl carrier protein isoforms from Cuphea lanceolata seeds in the de
      novo biosynthesis of medium-chain fatty acids.
AB  - To investigate the role of acyl carrier protein (ACP) in determining the fate of
      the acyl moieties linked to it in the course of de-novo fatty acid biosynthesis
      in higher plants, we carried out in vitro experiments to reconstitute the fatty
      acid synthase (FAS) reaction in extracts of spinach (Spinacia oleracea L.)
      leaves, rape (Brassica napus L.) seeds and Cuphea lanceolata Ait. seeds. The
      action of two major C. lanceolata ACP isoforms (ACP 1 and ACP 2) compared to ACP
      from Escherichia coli was monitored by saponification of the corresponding FAS
      products with subsequent analysis of the liberated fatty acids by high
      performance liquid chromatography. In a second approach the preference of the
      medium-chain acyl-ACP-specific thioesterase (EC 3.1.2.14) of C. lanceolata seeds
      for the hydrolysis of acyl-ACPs prepared from the three ACP types was
      investigated. Both ACP isoforms from C. lanceolata seeds supported the synthesis
      of medium-chain fatty acids in a reconstituted FAS reaction of spinach leaf
      extracts. Compared to the isoform ACP 1, ACP 2 was more effective in supporting
      the synthesis of such fatty acids in the FAS reaction of rape seed extracts and
      caused a higher accumulation of FAS products in all experiments. No preference of
      the medium-chain thioesterase for one specific ACP isoform was observed. The
      results indicate that the presence of ACP 2 is essential for the synthesis of
      decanoic acid in C. lanceolata seeds, and its expression in the phase of
      accumulation of high levels of this fatty acid provides an additional and highly
      efficient cofactor for stimulating the FAS reaction.

PMID- 9637072
TI  - Photoinhibitory damage is modulated by the rate of photosynthesis and by the
      photosystem II light-harvesting chlorophyll antenna size.
AB  - We investigated the effect of photosynthetic electron transport and of the
      photosystem II (PSII) chlorophyll (Chl) antenna size on the rate of PSII
      photoinhibitory damage. To modulate the rate of photosynthesis and the light
      harvesting capacity in the unicellular chlorophyte Dunaliella salina Teod., we
      varied the amount of inorganic carbon in the culture medium. Cells were grown
      under high irradiance either with a limiting supply of inorganic carbon, provided
      by an initial concentration of 25 mM NaHCO3, or with supplemental CO2 bubbled in
      the form of 3% CO2 in air. The NaHCO3-grown cells displayed slow rates of
      photosynthesis and had a small PSII light-harvesting Chl antenna size (60 Chl
      molecules). The half-time of PSII photodamage was 40 min. When switched to
      supplemental CO2 conditions, the rate of photodamage was retarded to a t1/2 = 70
      min. Conversely, CO2-supplemented cells displayed faster rates of photosynthesis
      and a larger PSII light-harvesting Chl antenna size (500 Chl molecules). They
      also showed a rate of photodamage with t1/2 = 40 min. When depleted of CO2, the
      rate of photodamage was accelerated (t1/2 = 20 min). These results indicate that
      the in-vivo susceptibility to photodamage is modulated by the rate of forward
      electron transport through PSII. Moreover, a large Chl antenna size enhances the
      rate of light absorption and photodamage and, therefore, counters the mitigating
      effect of forward electron transport. We propose that under steady-state
      photosynthesis, the rate of light absorption (determined by incident light
      intensity and PS Chl antenna size) and the rate of forward electron transport
      (determined by CO2 availability) modulate the oxidation/reduction state of the
      primary PSII acceptor QA, which in turn defines the low/high probability for
      photodamage in the PSII reaction center.

PMID- 9637073
TI  - Nectar-carbohydrate production and composition vary in relation to nectary
      anatomy and location within individual flowers of several species of
      Brassicaceae.
AB  - Nectar-carbohydrate production and composition were investigated by high
      performance liquid chromatography and enzymology in nine species from five tribes
      of the Brassicaceae. In six species (Arabidopsis thaliana (L.) Heynh., Brassica
      napus L., B. rapa L., Lobularia maritima (L.) Desv., Raphanus sativus L., Sinapis
      arvensis L.) that produced nectar from both lateral nectaries (associated with
      the short stamens) and median nectaries (outside the long stamens), on average
      95% of the total nectar carbohydrate was collected from the lateral ones. Nectar
      from these glands possessed a higher glucose/fructose ratio (usually 1.0-1.2)
      than that from the median nectaries (0.2-0.9) within the same flower.
      Comparatively little sucrose was detected in any nectar samples except from
      Matthiola bicornus (Sibth. et Sm.) DC., which possessed lateral nectaries only
      and produced a sucrose-dominant exudate. The anatomy of the nectarial tissue in
      nectar-secreting flowers of six species, Hesperis matronalis L., L. maritima, M.
      bicornus, R. sativus, S. arvensis, and Sisymbrium loeselii L., was studied by
      light and scanning-electron microscopy. Phloem alone supplied the nectaries.
      However, in accordance with their overall nectar-carbohydrate production, the
      lateral glands received relatively rich quantities of phloem that penetrated far
      into the glandular tissue, whereas median glands were supplied with phloem that
      often barely innervated them. All nectarial tissue possessed modified stomata
      (with the exception of the median glands of S. loeselii, which did not produce
      nectar); further evidence was gathered to indicate that these structures do not
      regulate nectar flow by guard-cell movements. The numbers of modified stomata per
      gland showed no relation to nectar-carbohydrate production. Taken together, the
      data on nectar biochemistry and nectary anatomy indicate the existence of two
      distinct nectary types in those Brassicacean species that possess both lateral
      and median nectaries, regardless of whether nectarial tissue is united around the
      entire receptacle or not. It is proposed that the term "nectarium" be used to
      represent collectively the multiple nectaries that can be found in individual
      flowers.

PMID- 9637074
TI  - Compliance strategies and regulatory effectiveness of performance-based
      regulation of chemical accident risks.
AB  - This paper investigates the role that performance-based regulations can play in
      linking a firm's environmental, health, and safety concerns with their corporate
      strategy. The specific focus is on the performance standards required by the
      Clean Air Act Amendments (CAAA) which require firms that store or use certain
      chemicals to develop a Risk Management Plan (RMP) for reducing the likelihood and
      impact of accidents at their plants. Data from a series of case studies and
      interviews of executives in chemical firms reveal that proactive companies
      integrated many of the requirements of the CAAA into their management systems
      prior to the regulatory requirements. Most of these firms tend to be large ones.
      Small firms often lack the resources to implement these regulations and hence
      have tended to have a more difficult time with compliance.

PMID- 9637075
TI  - Utilizing third-party inspections for preventing major chemical accidents.
AB  - This paper proposes using certified third parties, coupled with Model Risk
      Management Programs (Model RMPs), to implement EPA's Proposed Rule on the
      prevention of chemical accidental releases. We concentrate on the insurance
      aspects of this third-party approach and show that it could enable insurers to
      more cost-effectively provide coverage against the risks of chemical accidental
      releases. The third-party approach may also signal the facility's safety and
      reduce the enforcement costs of regulations.

PMID- 9637076
TI  - A pharmacokinetic study of occupational and environmental benzene exposure with
      regard to gender.
AB  - Using physiologically-based pharmacokinetic (PBPK) modeling, occupational,
      personal, and environmental benzene exposure scenarios are simulated for adult
      men and women. This research identifies differences in internal exposure due to
      physiological and biochemical gender differences. Physiological and chemical
      specific model parameters were obtained from other studies reported in the
      literature and medical texts for the subjects of interest. Women were found to
      have a higher blood/air partition coefficient and maximum velocity of metabolism
      for benzene than men (the two most sensitive parameters affecting gender-specific
      differences). Additionally, women generally have a higher body fat percentage
      than men. These factors influence the internal exposure incurred by the subjects
      and should be considered when conducting a risk assessment. Results demonstrated
      that physicochemical gender differences result in women metabolizing 23-26% more
      benzene than men when subject to the same exposure scenario even though benzene
      blood concentration levels are generally higher in men. These results suggest
      that women may be at significantly higher risk for certain effects of benzene
      exposure. Thus, exposure standards based on data from male subjects may not be
      protective for the female population.

PMID- 9637077
TI  - Lognormal distributions for total water intake and tap water intake by pregnant
      and lactating women in the United States.
AB  - Using probability plots and Maximum Likelihood Estimation (MLE), we fit lognormal
      distributions to data compiled by Ershow et al. for daily intake of total water
      and tap water by three groups of women (controls, pregnant, and lactating; all
      between 15-49 years of age) in the United States. We also develop bivariate
      lognormal distributions for the joint distribution of water ingestion and body
      weight for these three groups. Overall, we recommend the marginal distributions
      for water intake as fit by MLE for use in human health risk assessments.

PMID- 9637078
TI  - Analysis of exogenous components of mortality risks.
AB  - A new technique for deriving exogenous components of mortality risks from
      national vital statistics has been developed. Each observed death rate Dij (where
      i corresponds to calendar time (year or interval of years) and j denotes the
      number of corresponding age group) was represented as Dij = Aj + BiCj, and
      unknown quantities Aj, Bi, and Cj were estimated by a special procedure using the
      least-squares principle. The coefficients of variation do not exceed 10%. It is
      shown that the term Aj can be interpreted as the endogenous and the second term
      BiCj as the exogenous components of the death rate. The aggregate of endogenous
      components Aj can be described by a regression function, corresponding to the
      Gompertz-Makeham law, A(tau) = gamma + beta x e alpha tau, where gamma, beta, and
      alpha are constants, tau is age, A(tau) [symbol: see text] tau = tau j identical
      to A(tau j) identical to Aj and tau j is the value of age tau in jth age group.
      The coefficients of variation for such a representation does not exceed 4%. An
      analysis of exogenous risk levels in the Moscow and Russian populations during
      1980-1995 shows that since 1992 all components of exogenous risk in the Moscow
      population had been increasing up to 1994. The greatest contribution to the total
      level of exogenous risk was lethal diseases, and their death rate was 387 deaths
      per 100,000 persons in 1994, i.e., 61.9% of all deaths. The dynamics of exogenous
      mortality risk change during 1990-1994 in the Moscow population and in the
      Russian population without Moscow had been identical: the risk had been
      increasing and its value in the Russian population had been higher than that in
      the Moscow population.

PMID- 9637079
TI  - [Value of imaging in the assessment of malignant fibrous histiocytoma of the soft
      tissues].
AB  - Malignant fibrous histiocytoma (MFH) is a rare and potentially highly malignant
      sarcoma. The authors report 6 cases of MFH in various sites: two in the chest
      wall, one in the pelvis, two in the gluteal zones and one on the scalp.
      Ultrasonography and computed tomography were the main imaging methods used in the
      assessment of the structure and extension of the tumor. A poor prognosis was
      noted in four cases: death within a few months in the two thoracic sites,
      recurrence in the pelvic and scalp lesions, radical surgery allowed recovery in
      two cases. A review of the literature showed that MRI and CT are complementary in
      the initial staging and follow-up of these patients.

PMID- 9637080
TI  - [Ultrasound signs of pseudoneoplastic forms of hepatic hydatid cysts. A
      prospective analysis of 50 cases].
AB  - Pseudoneoplastic hydatid cyst of the liver (type IV), still raises diagnostic
      difficulties on ultrasonography (US), and often leads us to perform computed
      tomography. We therefore, conducted a prospective study of 50 cases of hepatic
      hydatid cyst (HHC) type IV in order to define the US and Doppler features
      allowing easy diagnosis with the best cost-effectiveness ratio. HHC type IV
      represented 23.7% of all types. The average age was 43.5 years with a female
      predominance. Many signs were described and their frequency was established. The
      main signs were daughter cysts (82%), hypo or hyperechoic spirals (66%), and
      peripheral transonic collarette (54%). At least one of these signs was present in
      90% of cases. The Doppler study showed the avascular nature of the lesion in 100%
      of cases. Hydatid serology using modern immunologic techniques confirmed the
      diagnosis in 74% of cases. The US-serology combination can establish the positive
      diagnosis of HHC type IV in 94% of cases. Computed tomography therefore has a
      small place in this setting.

PMID- 9637081
TI  - [Contribution of imaging in the diagnosis of pulmonary alveolar proteinosis.
      Apropos of 3 cases].

PMID- 9637082
TI  - [Leiomyosarcoma of the inferior vena cava and magnetic resonance imaging].
AB  - Venous leiomyosarcomas are rare and predominantly arise in the inferior vena cava
      (IVC). The clinical findings, often not very suggestive and nonspecific,
      sometimes precede the diagnosis by several years. According to the literature,
      leiomyosarcoma of the IVC generally occurs in middle-aged women. Modern imaging
      techniques, especially magnetic resonance imaging (MRI) can now establish the
      diagnosis of leiomyosarcoma of the IVC with a high probability and allow
      assessment of operability. The authors report a case of leiomyosarcoma of the IVC
      in a 24-year-old male patient, confirmed by intravenous biopsy. They present the
      MR features of this malignant tumour, rarely reported in the literature, and
      emphasize the value of this examination in the operability staging. The 3D
      imaging provided by MRI allows intra and extraluminal staging and involvement of
      adjacent organs. It also allows optimal evaluation of the effects on flow,
      circulatory slowing or thrombosis and, due to its high contrast resolution, it is
      more sensitive to distinguish clot from tumour nodule.

PMID- 9637083
TI  - [Upper esophageal duplication. Apropos of a case disclosed by respiratory
      distress].
AB  - The authors report a new case of cystic oesophageal duplication, discovered in a
      10-month-old infant. This case is unusual because of its site: thoraco-cervical,
      and its acute clinical manifestations: respiratory depression. A surgical
      resection was performed after Barium swallow, chest X-ray and ultrasonography.
      Surgery ensured rapid clinical improvement. Pathology confirmed the diagnosis of
      cystic oesophageal duplication.

PMID- 9637085
TI  - [Hereditary osteo-onychodystosis. Apropos of 2 orthopedic cases].

PMID- 9637084
TI  - [Peritoneal splenosis. Apropos of a case: contribution of ultrasonography and
      computerized tomography].
AB  - The authors report a case of peritoneal splenosis: the initial diagnosis was
      established at ultrasound examination and CT scan. This unusual lesion must be
      suggested when the past history is significant, as asymptomatic should not be
      removed.

PMID- 9637086
TI  - [Renal needle biopsy in children. Technical aspects and results].
AB  - Renal needle biopsy is still irreplaceable in children. The objectives of this
      retrospective study were to specify the technical aspects and the main
      nephropathies encountered. 152 children under the age of 16 years (13 +/- 3), 79
      boys and 73 girls, underwent renal biopsy. The biopsy was performed after
      radiographic detection in 71 cases, and under continuous ultrasound guidance in
      81 cases. The comparative study of these 2 techniques revealed the superiority of
      continuous ultrasound guidance, allowing biopsy of an essentially cortical
      fragment, rich in glomeruli with a limited number of punctures. Histological
      examination showed a predominance of glomerular nephropathy with, especially,
      visually normal kidney and membranoproliferative glomerulonephritis. These data
      encourage us to perform ultrasound-guided RNB in children and to eradicate sites
      of infection, particularly involving the upper respiratory tract.

PMID- 9637087
TI  - [Pyramido-lunar fusion in black Africans. Apropos of 32 cases].
AB  - Lunotriquetral coalition is a congenital carpal anomaly rarely discovered in a
      white population. In the black population, most cases have concerned blacks in
      America, Australia and South Africa. In the Sub-Saharia area, in Senegal, the
      authors, after 8 incidental cases, report 32 lunotriquetral coalitions collected
      in 20 patients. This retrospective study comparatively analysed 361 X-rays of the
      wrist performed between February 1989 and July 1992 in the Orthopaedic and
      Traumatologic Center (CTO) in Dakar. The bony coalition was bilateral in 12
      patients and unilateral in the other 8 cases. The complete form (type III) was
      the most frequent (46.8%). In the bilateral forms, 5 patients presented this
      complete form. Lunotriquetral coalition was associated, in absence of congenital
      abnormalities, with a synovial cyst of the wrist (2 cases), scaphoid fracture (1
      case), non-union of a scaphoid fracture (1 case) and osteoarthritis of the wrist
      (2 cases). After review of the literature, the authors discuss racial factors,
      anatomo-radiographic forms and associated injuries.

PMID- 9637088
TI  - [Contribution of imaging in intestinal intussusception in the adult. Apropos of a
      case of ileocolic intussusception secondary to cecal lipoma].
AB  - On the basis of a case of ileocolonic intussusception in a 35-year-old patient
      secondary to an obstructive lipoma of the caecum, the authors review the
      literature and discuss the clinical and radiological aspects of this disease. The
      diagnosis was established by CT scan and barium enema before surgery. Adult
      intussusception is a rare disease, which does not have any specific clinical
      features. Radiological imaging is the only complementary investigation which can
      suggest the diagnosis.

PMID- 9637089
TI  - [Audiological management of children with malformations of the ear].
AB  - All cases of malformation of the ear must undergo audiological assessment. Before
      the age of 6 months, evoked auditory potentials during natural sleep will give
      information on the threshold for the high frequencies in both ears, and will
      confirm that the inner ear is functioning. After the age of 6 to 7 months,
      subjective tests are used to demonstrate the bone conduction thresholds and
      sometimes (depending on the degree of cooperation of the child) 1 or 2 air
      conduction curves. When the malformation is unilateral, and the hearing is normal
      on the opposite side, regular follow-up is required. When the malformation is
      bilateral, or unilateral in conjunction with a sensorineural hearing loss in the
      opposite ear, the child must be treated as a deaf child, and provided with a
      hearing aid.

PMID- 9637090
TI  - [Cochlear implants in the elderly].
AB  - The authors present a retrospective and multicenter study of 18 elderly patients
      aged above 60 years-old who underwent a cochlear implantation by comparing them
      with a population of adult patients. The purpose of this study is to evaluate the
      utility and benefits of cochlear implantation in the elderly by analyzing the
      clinical data and the results of a questionnaire assessing the use of the implant
      and the consequences of implantation on the quality of life. The results of this
      study indicate that the improvement of quality of life in the elderly is similar
      compared to a control group of adult patients.

PMID- 9637091
TI  - [Conservation of residual hearing after cochlear implantation].
AB  - Indications for cochlear implantation have been expanded to include severely
      hearing impaired adults and may increase the number of patients presenting with
      preoperative residual hearing. Conservation of residual hearing may allow better
      performance with an implant. However, conventional thought is that implantation
      destroys auditory structures involved in residual hearing. This study was
      undertaken to assess if there are general or surgical factors intervening in the
      conservation of residual hearing in a sample of multichannel implant recipients.
      A retrospective study on 50 adult cochlear recipients with preoperative residual
      hearing has been undertaken. Sixteen of 50 implanted subjects (32%) were found to
      have conserved their residual hearing. Among them, seven patients have clinically
      non-significant changes of hearing. Age, side of implantation, gender and
      etiology did not influence the outcome of residual hearing. Round window
      ossification, ossification of the cochlea, length of insertion, approach and site
      of insertion (scala tympani vs.scala vestibuli) were not found to be
      statistically significant between the population having lost and the population
      having conserved residual hearing. This study emphasizes the need to undertake a
      larger multicenter longitudinal study to determine the existence of factors
      related to the conservation of residual hearing.

PMID- 9637092
TI  - [From the classification of dysarthria to therapeutic concepts].
AB  - The wide definition of dysarthria includes not only involvement of speech and
      language, but also of the voice. The authors put forward a classification which
      is based more logically on the mechanisms of the disorders as they present, and
      which can at the same time serve as a guide to treatment.

PMID- 9637093
TI  - [Presentation of various treatments proposed for dystonic dysarthria].
AB  - Dystonia is characterised by purposeless muscle contractions, and can be
      expressed in many clinical forms, those involving the head and neck may cause
      problems with phonation, respiration or deglutition. The authors describe the
      various treatment options, both therapeutic, medical, rehabilitative and
      surgical.

PMID- 9637094
TI  - [Comparison of different phonetic materials for perceptive analysis of
      dysphonia].
AB  - The authors describe a prospective study whose aim was to analyse the influence
      of the choice of phonetic material on the judgment of the panel. De Krom has
      already reported an experiment in which perceptive analysis showed that a
      sustained vowel was a useful material provided that the attack transitory was
      included (so called complete sustained vowel). He also showed that the panel gave
      more consistent results with speech or the complete sustained vowel than with the
      stable part of the sustained vowel. Our first objective was to find out whether
      we agreed with Krom's results, because for the study in the Dutch language to be
      applied to the French language, it was necessary to carry out an experimental
      validation given the cultural differences which might prejudice the results. In
      additional, we thought it likely that some acoustic information which was present
      in the attack transitories and was lacking in the stable part of the sustained
      vowel would run the risk of under-valuing the dysphonia in a study carried out on
      the stable part of sustained vowels. Our second objective was therefore to
      demonstrate that in cases of dysphonia, assessment based on the stable part of
      sustained vowels would be more lenient than those based on speech. The study was
      carried out using 80 voice samples from 60 dysphonic patients and 20 control
      subjects. The panel was made up of 7 experienced listeners. Agreement in the jury
      was judged by the percentage of identical responses given on 3 different
      presentations of each speech sample. This study showed no differences in the
      agreement of panel members over the three types of material by changing the
      severity of classification by the panel was analysed as follows: 1--Pearson r
      correlation coefficient, comparing on the one hand speech (the reference
      variable), and on the other samples of the complete vowel and the isolated stable
      part of the valve (tested variables). 2--A linear regression analysis. Our
      results confirm that assessments carried out on a sustain/vowel tend to cause a
      more lenient assessment than those carried out on speech. The assessment carried
      out on sustained vowels when the attack transient is included were of similar
      valued to those carried out using speech.

PMID- 9637095
TI  - [Gastroesophageal reflux and dysphonia in children].
AB  - With the exception of congenital anomalies, the aetiology of dysphonia in
      children is often unknown. Yet, in adults, GOR has been shown to play an
      important role. 22 children (aged between 2 and 14 years, 14 boys and 8 girls),
      who had been suffering from a chronic dysphonia for more than six months were
      seen at consultation. After a clinical ENT examination including a fibreoptic
      laryngoscopy, each child had a long duration pH-study that lasted approximately
      24 hours. Using the classical criteria for GOR, a pathological GOR was discovered
      in 14 children, ie 64%. Analysis of the pH traces revealed that the vast majority
      of refluxes occurred when the child was awake. CONCLUSION: more than 64% of
      children suffering from chronic dysphonia had pathological GOR. The pH traces
      highlighted that the majority of these refluxes occurred when the child was
      awake.

PMID- 9637096
TI  - [Is laryngeal papillomatosis always juvenile?].
AB  - After recording an increased frequency of adult-onset recurrent respiratory
      papillomatosis, the authors propose a multicentric investigation. The aim of the
      investigation is to determinate the frequency of the new cases and their clinical
      form. The preliminary results confirm the increased frequency of the adult-onset
      form and show the possibility of a clinical form change.

PMID- 9637097
TI  - [Idiopathic recurrent paralysis. Retrospective analysis of 67 cases].
AB  - Sometimes incorrectly termed paralyses, idiopathic abnormalities of laryngeal
      movement pose many problems about their physiopathological mechanism and
      treatment. In an analysis of 67 cases, the outcome as far as the voice was
      concerned was favourable in 51 cases, but a return to normal mobility occurred in
      only 26 cases. An important factor is the delay before treatment is instituted.
      In addition to repeated investigation of the areas of ENT, neurology, chest and
      speech therapy, laryngeal electromyography can yield useful information, and
      should always be undertaken before surgery is advised. As long as the clinical
      conditions remains unimproved, the question of its idiopathic nature must be
      constantly reviewed. A multicentre standardised investigation into this condition
      would seem desirable to shed further light on its pathology and outcome.

PMID- 9637098
TI  - [Early, middle-latency and late auditory evoked potentials in a case of acquired
      epileptic aphasia (Landau-Kleffner syndrome)].
AB  - The authors report the case of a girl whose development was normal until the age
      of eleven when epileptic seizures occurred. These were followed by loss of speech
      and auditory agnosia. The diagnosis of Landau-Kleffner syndrome was mode. The
      study of the auditory evoked response showed normal function of ear and brainstem
      auditory relays. On the other hand, the amplitude of the middle latency and late
      cortical responses were decreased. The relationship between these
      electrophysiological abnormalities and auditory agnosia are discussed.

PMID- 9637099
TI  - [Objective tinnitus and velar myoclonus: apropos of a case of a child].
AB  - The syndrome in which velar myoclonus is associated with objective tinnitus is
      rare, and in the adult corresponds most commonly with a lesion in the dentato
      rubro-olivary tract. In the child, no lesion can usually be found. The disorders
      of function resulting from this syndrome are very disabling. Many forms of
      treatment have been proposed, and the results have been found to be
      disappointing. The authors report the case of a child in which muscle relaxants
      were used to very good effect, and emphasize the fact that the natural history of
      the condition in childhood is one of spontaneous remission, so that aggressive
      treatment is not appropriate.

PMID- 9637100
TI  - [ORL and speech aspects in DiGeorge syndrome].
AB  - The DiGeorge syndrome presents clinically as a combination of a congenital
      cardiopathy with immune deficiency and predisposition to infections, signs of
      hypoparathyroidis with severe hypocalcaemia in the neonatal period, and facial
      dysmorphism. New techniques in molecular cytogenetics (in-situ fluorescent
      hybridisation--FISH) have provided evidence of microdeletion of chromosome 22q11
      in most cases of the DiGeorge syndrome. There is an important overlap between
      this syndrome, the velo-cardio-facial syndrome, and certain other cono-truncal
      cardiac anomalies which are linked with the same microdeletion syndrome. Basing
      their observation on a case of the partial syndrome, the authors emphasise the
      otological and maxillo-facial aspects, and especially the effects on speech and
      language. It is essential to carry out repeated audiometric testing to exclude an
      audiometric cause for the speech and language problems. At the same time,
      thorough speech and language assessment is necessary to establish the degree of
      velar insufficiency (rhinolalia). These will guide the speech therapy
      rehabilitation, and quantify the psycho-affective component. Surgery on the
      palate may be a possibility, depending on the progress in speech and language
      improvement.

PMID- 9637101
TI  - Screening for otitis media with effusion in Chinese schoolchildren: a pilot
      study.
AB  - Otitis media with effusion (OME) is a common childhood otological condition. The
      treatment of OME with myringotomy and grommet insertion is the commonest surgical
      procedure performed on children worldwide. Although the figure for the prevalence
      of OME is widely known in Caucasian children, figures are lacking for Chinese
      children. A pilot study for the prevalence of OME in Hong Kong Chinese
      schoolchildren was undertaken by the investigators on a group of 255 children
      with ages ranging from 6 to 7 years old. A point prevalence rate of 1.56% of OME
      was found. This is noticeably lower than studies in the West where the reported
      prevalence ranges from 2.3% to 14% in age compatible children. The epidemiology
      of OME and the methodology for population screening of OME are reviewed and
      discussed. The preliminary findings of this study would be a useful indicator for
      the estimation of study group size in a full epidemiological study of OME in
      Chinese children as well as providing valuable insight into the technical
      difficulties involved.

PMID- 9637102
TI  - [Malignant nasosinusal melanomas. Review of the literature apropos of 12 cases].
AB  - Malignant melanoma with primary onset in the nasal cavity and paranasal sinuses
      remains a scarcely encountered malignancy and we report 12 cases of our own
      experience from 1991. These mucosal melanomas occur mainly in the elderly and
      present most commonly as a one sided airway obstructive syndrome with often
      bleeding in the nasal cavity. No sex or race ratio is found. Histological
      examination of the surgical specimen has been made easier since the use of
      immunohistochemical studies. The original site of onset is commonly located at
      the inferior part of the nasal cavity but in many cases, it is noted several
      sites of tumor localization. Despite well conducted treatment the prognosis
      remains quite deceiving and significantly poor. In our study, the 4-year
      actuarial survival was 26%. The 5-year survival rate ranges in the literature
      from 10% to 40%. Short and long term follow-up show an important rate of
      recurrence (local and lymph node metastases as well as distant metastases). The
      insidious evolution of the malignancy usually happens during the first year.
      Computed tomography and MRI are essential in the evaluation of tumor extension.
      The treatment is based on the combination of surgery and radiotherapy: Surgery is
      practised first and must ensure sufficient excision of the tumor without minimal
      functional or aesthetic damage in this complex region. This surgery is based on
      surgical approaches to the midface known as Lateral rhinotomy and midfacial
      degloving. When there is cervical lymph node involvement at the time of diagnosis
      it is suitable to treat it, even in case of recurrence. Complementary high dose
      radiation is required to treat tumors which could not undergo surgery and also as
      adjuvant therapy after removal of the mass.

PMID- 9637103
TI  - Identification of the HSV-1 genome by "Dot Blot hybridization" in the geniculate
      ganglion of rabbits.
AB  - Herpes simplex Virus type 1 (HSV-1) was inoculated into 48 rabbits by 3 different
      routes: 10 rabbits were dosed by mouth, 18 rabbits injected in the tongue and 14
      injected in the perineurium of the facial nerve at its entrance into the
      stylomastoid foramen. Some of the animals were killed after a week and others
      after three weeks. Facial palsy was produced in none of the cases. Seroconversion
      was demonstrated in the peripheral blood of 100% of the inoculated animals.
      Cultures of macerate of the facial nerve and geniculate ganglion, as well as of
      the ipsilateral medulla, were negative. DNA from HSV-1 was found by "Dot Blot
      hybridization" technique in 30% of the macerates of the geniculate ganglion and
      facial nerve and in 60% of the medulla macerate in those animals killed after one
      week and in 0% of both samples in those killed in the third week. The fact that
      the HSV-1 could be isolated in the geniculate ganglion of the facial nerve
      continues to support the possibility of this virus as the causal agent for facial
      palsy, either as a single disease or associated with other symptoms.

PMID- 9637104
TI  - Waldeyer's ring lymphomas: an epidemiological study of 55 cases.
AB  - Waldeyer's ring is a relatively common location for non-Hodgkin's lymphoma. Here,
      we report an epidemiological study of Waldeyer's ring lymphomas based on data for
      55 cases treated over a 19-year period at three centers in northern Spain. In
      most respects our results confirm those of previous studies. The average delay
      between first consultation and diagnosis was 3.8 months, and was longer for
      nasopharyngeal lymphomas than for tonsillar lymphomas.

PMID- 9637105
TI  - [The N0 neck in patients treated by supraglottic laryngectomy: abstention,
      surgery or radiotherapy?].
AB  - The authors examined the therapeutical approach to the N0 neck in patients
      submitted to supraglottic laryngectomy (SL). In these patients the choice of the
      therapeutical protocol may consist of simple abstention, of neck dissection or of
      elective radiotherapy: every decision has to be taken considering all specific
      inconveniences of each option. In their report the authors examined the follow-up
      of the N0 necks of 421 patients submitted to SL from 1970 to 1991. The patients
      submitted to wait and see policy were 225 whereas 196 received uni- or bilateral
      neck dissection. After the cervical failure's salvage the final 3-years control
      of the neck was the same in the two groups (91.1% vs 91.4%). In a previous
      research on 1157 N0 necks of patients submitted to total laryngectomy they
      observed a 5-years cervical control of 88.8% after wait and see policy and of
      92.3% after elective radiotherapy. The conclusions of the authors is that no one
      of the two protocols is preferable to the other one and that subsequently in many
      cases of supraglottic T1 and T2 cancers a wait and see policy may be justified in
      absence of consistent counter-indications.

PMID- 9637106
TI  - Tracheal ring rupture and herniation during percutaneous dilatational
      tracheostomy identified by fibreoptic bronchoscopy.
AB  - We present a case of rupture and herniation of cartilaginous tracheal rings into
      the lumen of the trachea that was noticed as an incidental finding during
      bronchoscopy after percutaneous dilatational tracheostomy. While percutaneous
      methods of tracheostomy formation gain popularity in intensive care settings, the
      number of reported problems associated with this technique continue to grow. We
      propose that fibreoptic bronchoscopy used routinely with percutaneous
      tracheostomy formation will identify a number of complications involving the
      tracheal skeleton.

PMID- 9637107
TI  - [Laryngeal tuberculosis: a diagnosis not to be forgotten].
AB  - Tuberculosis of the larynx has become a rarity since the discovery of
      streptomycin in 1944. In this article a personal case history is described,
      together with a review of the literature and an analysis of the main clinical
      features of tuberculosis of the larynx. The pseudo-tumoural form of tuberculosis
      is often indicative of the presence of pulmonary tuberculosis, but may also occur
      in isolation. Histology is often the only definitive diagnostic test.

PMID- 9637108
TI  - [Lingual thyroid and intra-lingual thyroglossal cyst. Apropos of 2 cases].
AB  - Lingual thyroid and intra lingual thyro-glossal cyst are two benign tumours of
      similar embryological pathogenesis respectively with the arrest in the ectopic
      position of the thyroid gland during its downward migration and from abnormal
      persistence of the thyro-glossal tract for the cyst. The occurrence of lingual
      thyroid is rare 1/100,000 patients and outnumbers the incidence of intra-lingual
      cyst which represents an estimated 2.1% of the thyro-glossal cysts or fistulas.
      Both lesions are a rare cause of dysphagia and dyspnoea due to oropharyngeal
      obstruction, and radionuclide scintigraphy combined with CT and/or MRI will
      establish the diagnosis. Surgical pharyngotomy with an infra-hyoid approach
      provides excellent access to the lesions and complete removal of the tumours.

PMID- 9637109
TI  - Diagnosis and treatment of lingual thyroid: a review.
AB  - Lingual thyroid is a rare developmental anomaly. It occurs because of the
      defective descent of thyroid tissue through the thyroglossal duct to its normal
      pretracheal position. In this study, two patients who presented with a mass in
      the oropharynx, finally diagnosed as lingual thyroid are presented, and the
      literature is reviewed. The masses were 3 x 2.5 x 1.5 cm and 3.5 x 3 x 3 cm in
      size. The diagnosis was based on the clinical features, fine needle aspiration
      biopsy, laboratory tests and radiographic imaging studies. The first case was
      treated medically with thyroxine. No treatment was given for the second case
      because of the patient's refusal. Both cases have not required additional therapy
      so far.

PMID- 9637110
TI  - [Chronic osteomatous otitis media: apropos of 2 cases].
AB  - Osteomatous chronic otitis media is an extremely rare clinical entity. Fleury has
      described three types: a massive type, a diffuse attico-antral type, and a
      localised type. This latter is equivalent to a state of chronic inflammation of
      the middle or outer ear, accompanied by bony excresscences of osteomatous type.
      Here we add two additional cases to the few which are to be found in the
      literature on this subject. We would also like to emphasize the practical
      surgical difficulty of treating such cases, with the vital structures of the
      middle ear hidden (facial nerve, lateral semicircular canal, and ossicles), and
      would advise the greatest care when tackling these surgically.

PMID- 9637111
TI  - [Pulsatile tinnitus caused by pre-auricular post-traumatic vascular lesions:
      apropos of a case].
AB  - Pulsatile tinnitus associated with a pulsating swelling were the presenting
      clinical features of a patient who had suffered contusion to the pre-auricular
      area. The diagnosis of arteriovenous fistula (AVF) was made, and the child
      underwent operation. The pathology of this condition is reviewed.

PMID- 9637112
TI  - Nasal chondroma: a case report and review of the literature.
AB  - Although rare tumors, chondromas will on occasion be encountered by the
      otolaryngologist in his routine daily practice. The authors describe a nasal
      myxochondroma in an 8-year-old child, which was removed satisfactorily
      surgically, with no signs of recurrence even after 4 years of follow-up. Because
      chondromas may also present as nasal polyps, the knowledge of cartilaginous
      tumors in the nose plays a pivotal role for a better approach to these patients.

PMID- 9637113
TI  - [Hypoglosso-facial anastomosis: results and technical development towards end-to
      side anastomosis with rerouting of the intra-temporal facial nerve (modified May
      technique)].
AB  - The authors report their experience with 31 hypoglosso-facial anastomoses mainly
      carried out after removal of tumours of the cerebello-pontine angle, 26 were
      available for evaluation: at 18 months there were 5 of grade II, 19 of grade IV
      and 2 of grade V. Only one patient was dissatisfied with the result. 24 of the
      patients had received their hypoglosso-facial anastomosis using the clinical
      technique of Korte. In 3 cases the operation was by the technique of May. The
      authors suggest a variation of May's technique: it was carried out on the last 4
      patients. It consists of a hemi-hypoglosso-facial anastomosis with rerouting of
      the mastoid portion of the facial nerve, without using a nerve graft. The aim of
      this technique is to reduce the sequelae of hemi-lingual atrophy and paralysis
      (which gives trouble with articulation, mastication and deglutition). The
      authors' experience confirms that these sequelae are greatly reduced, if not
      abolished. The functional results in terms of facial movements were satisfactory
      and consistant: 43.7% were quantified--with 3 of grade II and one of grade IV on
      the House Brackmann scale.

PMID- 9637114
TI  - [External otitis].

PMID- 9637115
TI  - GnRH agonists and add-back therapy: is there a perfect combination?

PMID- 9637116
TI  - Can women at risk of cervical abnormality be identified?
AB  - OBJECTIVE: To determine if use of a detailed risk factor profile accurately
      predicts the presence of cytological abnormality of the cervix or improves the
      appropriateness of referral for colposcopic assessment when women are found to
      have these abnormalities. DESIGN: Cross-sectional survey. SETTING: Family
      planning clinic. POPULATION: 1219 consecutive women, aged between 15 and 19
      years, attending for contraceptive advice. Variables included age, social class,
      educational status, hormonal and obstetric history, smoking and alcohol habits,
      history of sexually transmitted diseases, the age of first intercourse, number of
      sexual partners, duration of each relationship, frequency of intercourse,
      contraception used and the age of each partner. MAIN OUTCOME MEASURES: Presence
      or absence of cytological abnormality and the presence or absence of histological
      abnormality in those with cytological abnormality referred for colposcopic
      assessment. RESULTS: Univariate analysis confirmed many of the known associations
      of cervical abnormality. Discriminant analysis identified five independent
      significant predictors of cytological abnormality and four independent predictors
      of dyskaryotic cytology. At best models, derived from identified variables
      correctly predicted 10.1% of individuals with cytological abnormality and 13.5%
      of those with dyskaryotic cytology. Of those referred for colposcopic assessment
      because of abnormal cytology, models were able to predict 23.5% of those with
      histological evidence of cervical intraepithelial neoplasia. CONCLUSIONS: Despite
      the availability of detailed information regarding the known correlates of
      cervical neoplasia in this age group, it was not possible to identify the
      majority of women with cervical abnormality. It is concluded that the strength of
      these associations is not sufficient to allow useful prediction of membership of
      a high risk group.

PMID- 9637117
TI  - A systematic review and meta-analysis of family history and risk of ovarian
      cancer.
AB  - OBJECTIVE: To estimate the relative risk and lifetime risk of ovarian cancer in
      women with various categories of family history. DESIGN: A meta-analysis of all
      published case-control and cohort studies. METHODS: Pooled relative risk
      estimates were calculated for the case control studies, using the Mantel-Haenzel
      method. These estimates were combined with the relative risks from the cohort
      studies. The pooled estimates of relative risk were used to estimate lifetime
      risks of ovarian cancer from age 15 up to age 75, for various categories of
      family history. MAIN OUTCOME MEASURES: Relative risks and lifetime risks of
      developing ovarian cancer were calculated for the categories of women with 1. an
      affected first degree relative; 2. an affected mother; 3. an affected sister; and
      4. women with more than one affected relative. RESULTS: The relative risk to
      first degree relatives is 3.1 (95% CI 2.6-3.7). There is some evidence that this
      relative risk declines with age. The relative risk to mothers of cases 1.1 (95%
      CI 0.8-1.6) was lower than the relative risks to sisters: 3.8 (95% CI 2.9-5.1),
      and daughters: 6.0 (95% CI 3.0-11.9); the explanation of this difference is
      unclear. CONCLUSIONS: Women with a family history of ovarian cancer have a
      substantially higher risk of developing ovarian cancer compared with women
      without such a history. However the risk is small for most categories of family
      history, except for the small number of individuals who have more than one
      affected relative.

PMID- 9637118
TI  - Value of magnetic resonance imaging with an endovaginal receiver coil in the pre
      operative assessment of Stage I and IIa cervical neoplasia.
AB  - OBJECTIVE: To assess the value of high resolution endovaginal magnetic resonance
      images (MRI) of the uterine cervix in planning management of early cervical
      cancer. DESIGN: Prospective cross-sectional study. SETTING: Specialist
      gynaecological oncology unit of a postgraduate teaching hospital. PARTICIPANTS:
      Thirty nine women aged 25-76 years old (mean 42.5 years) with invasive carcinoma
      Stage I or IIa of the cervix. METHODS: A ring coil was positioned endovaginally
      around the cervix. Imaging was performed on a 1.0 T HPQ Vista or 0.5 T Asset
      (Picker, Highland Heights, Ohio, USA) using T1 weighted and T2 weighted sequences
      in transverse and sagittal planes with thin slices (2.5 mm) and small fields of
      view (12 cm). Tumour volumes were measured and any extension into adjacent organs
      and parametrium was noted. The patients were followed up after treatment and the
      outcome related to the MRI findings. RESULTS: There was one false positive and
      one false negative result among five Stage Ia patients being assessed for
      residual disease after cone biopsy or LLETZ. The MRI assessment of the size and
      distribution of the tumour was confirmed histologically in all 31 patients with
      Stage Ib or IIa disease who were treated surgically. One of these patients in
      whom no endocervical tumour was visible on MRI underwent radical trachelectomy.
      Three patients had radiotherapy as primary treatment. Patients with Stage Ib or
      IIa disease who had tumour volumes > 10 cm3 with early parametrial extension on
      MRI had a substantially worse prognosis at 24 months (disease-free survival 58.3%
      vs 95.5%, P = 0.003). CONCLUSION: High resolution MRI with an endovaginal coil
      allows precise measurement of tumour volume and identifies patients with small
      volume disease who might be considered for more conservative therapy. This
      technique also reveals early parametrial invasion that cannot be identified
      reliably by any other method. Early parametrial invasion in women with large
      tumours appears to have a very much worse prognosis.

PMID- 9637119
TI  - Pre-operative serum level of tumour-associated trypsin inhibitor and residual
      tumour size as prognostic indicators in Stage III epithelial ovarian cancer.
AB  - OBJECTIVE: To evaluate the use of the pre-operative tumour-associated trypsin
      inhibitor (TATI) level and residual tumour size at primary surgery as a
      prognostic indicators for patients with Stage III epithelial ovarian cancer.
      DESIGN: Retrospective cohort study. SETTING: Department of Obstetrics and
      Gynaecology, University Hospital, Helsinki, Finland. PARTICIPANTS: Ninety-eight
      women with Stage III ovarian cancer. METHODS: TATI was measured by
      radioimmunoassay from serum samples obtained within one week before surgery. A
      cutoff value of 22 microg/L was used. Multivariate analysis included pre
      operative TATI level, age, histologic grade and histologic type. Mantel-Cox test
      was used for calculating statistical significance of differences in survival
      between groups. MAIN OUTCOME MEASURES: Cumulative five-year survival, pre
      operative serum TATI level and residual tumour size. RESULTS: Surgery was optimal
      (residual tumour size < or = 2 cm) in 55 patients and suboptimal (residual tumour
      size > 2 cm) in 43. Pre-operative TATI level < or = 22 microg/L predicted better
      prognosis both in patients with optimal and suboptimal surgery compared with
      patients with pre-operative TATI level > 22 microg/L. Patients with optimal
      surgery and a pre-operative TATI > 22 microg/L had a twofold relative risk of
      death compared with those with a pre-operative TATI < or = 22 microg/L. The
      cumulative survival was less than three years for patients with suboptimal
      surgery and pre-operative TATI > 22 microg/L. CONCLUSIONS: Pre-operative serum
      TATI in combination with residual tumour size may be useful in stratifying
      patients with Stage III ovarian cancer into different categories in randomised
      treatment trials.

PMID- 9637120
TI  - A comparative study of pre-operative procedures to assess cervical invasion by
      endometrial carcinoma.
AB  - OBJECTIVE: To compare the accuracy of different diagnostic procedures currently
      used to assess cervical involvement in endometrial carcinoma. DESIGN:
      Retrospective observational study. SETTING: Department of Obstetrics and
      Gynecology, Shinshu University Hospital, Matsumoto, Japan. PARTICIPANTS: Sixty
      four patients with endometrial carcinoma were evaluated pre-operatively for
      cervical involvement by six different diagnostic procedures: cervical cytology,
      endocervical curettage, transvaginal ultrasonography, hysteroscopy, magnetic
      resonance imaging, and serum levels of CA125. The number of positive and negative
      diagnoses of cervical invasion by each of these procedures were correlated with
      the actual invasion determined by histological examination. RESULTS: Cervical
      invasion was confirmed in 12 (18.8%). Endocervical curettage showed high
      sensitivity (91%), the highest negative predictive value (96%), and the lowest
      negative likelihood ratio (0.14). Hysteroscopy showed high positive likelihood
      ratio (8.2) and low negative likelihood ratio (0.20). Magnetic resonance imaging
      showed the highest positive predictive value (75%) and the highest positive
      likelihood ratio (12.5). Magnetic resonance imaging was excellent for predicting
      stromal invasion, whereas hysteroscopy was superior for assessing mucosal
      involvement to magnetic resonance imaging. CONCLUSION: Endocervical curettage is
      a good test for excluding cervical involvement by endometrial carcinoma.
      Hysteroscopy is a good test in making both positive and negative diagnoses for
      cervical involvement. Magnetic resonance imaging is an excellent test for
      detecting cervical involvement, especially when the stroma is invaded.

PMID- 9637121
TI  - Uterine thermal balloon therapy for the treatment of menorrhagia: the first 300
      patients from a multi-centre study. International Collaborative Uterine Thermal
      Balloon Working Group.
AB  - OBJECTIVE: To evaluate the safety and efficacy of thermal balloon therapy for
      menorrhagia. DESIGN: Prospective, observational study. SETTING: Fifteen centres
      in Canada and Europe. POPULATION: Two hundred and ninety-six eligible women for
      whom follow up data were available for three months or more. Eligible women
      included those for whom further fertility was not a concern, were not
      postmenopausal, suffered from intractable menorrhagia, had a normal uterine
      cavity, and who were fully informed regarding the investigational nature of
      uterine thermal balloon therapy. METHODS: Three hundred and twenty-one procedures
      of balloon endometrial ablation were performed using the same protocol between
      June 1994 and August 1996. Exclusion criteria included structural uterine
      abnormality or (pre) malignant lesions. Treatment entailed controlled heating of
      fluid in an intrauterine balloon. General anaesthesia was employed in the 61% of
      procedures while local anaesthesia with or without sedation was used in 39% of
      cases. ANALYSIS: Follow up data at 3 and/or 6, and/or 12 months were required for
      inclusion in the analysis. A paired t test, Wilcoxon signed-ranks test, and
      multiple and logistic regression analyses were used to evaluate the changes in
      bleeding and dysmenorrhoea patterns, and possible confounding variables,
      respectively. Success was defined as the subjective reduction of menses to
      eumenorrhoea or less. RESULTS: No intra-operative complications occurred, and
      post-operative morbidity was minimal. Success of the procedure was constant over
      the year (range 88%-91%). Treatment led to a significant decrease in the duration
      of menstrual flow and severity of pain (P < 0.0001). Increasing age, higher
      balloon pressure, smaller uterine cavity, and a lesser degree of pre-procedure
      menorrhagia were associated with significantly improved results. Pre-treatment
      with gonadotrophin releasing hormone agonists increased amenorrhoea and spotting
      rates (P = 0.03), but was only used in 5% of cases. CONCLUSION: Thermal balloon
      endometrial ablation appears to be safe, as well as effective in properly
      selected women with menorrhagia and is potentially an outpatient procedure.

PMID- 9637122
TI  - Analysis of birthweight and gestational age in antepartum stillbirths.
AB  - OBJECTIVE: To study the characteristics of birthweight and gestational age of
      third trimester fetal deaths which occurred before the onset of labour. DESIGN:
      Review of computerised confidential perinatal mortality records. Data originated
      from the 1992 Trent Region Perinatal Mortality Survey. SAMPLE: One hundred and
      forty-nine antepartum stillbirths of at least 24 weeks of gestation confirmed by
      early ultrasound scan. Congenital abnormalities and multiple pregnancies were
      excluded. MAIN OUTCOME MEASURES: Reported causes of stillbirth; weight-for
      gestational age centiles based on a standard derived from normal pregnancies;
      pregnancy characteristics compared with the local maternity population. RESULTS:
      Of 149 stillbirths, 83 (56%) were preterm and 66 were at term, and the majority
      (126; 85%) occurred from 31 weeks. Most of the deaths (97; 65%) were reported as
      'unexplained' even though post-mortems had been carried out in 60% of all cases.
      Using a gestational age-specific fetal weight standard derived from normal, term
      live births, 41% of all cases of stillborn infants were small-for-gestational age
      (< 10th centile; OR 6.2; 95% CI 3.3-11.5); 39% of which had been classified as
      unexplained were small for gestational age (OR 5.6; 2.6-12.0). This excess of
      small stillbirths was most pronounced between 31 and 33 weeks, where the weights
      of 63% of all stillbirths and 72% of unexplained fetal deaths were < 10th
      centile. Overall, a higher proportion of preterm (< 37 weeks) than term
      stillbirths were small for gestational age: 53% vs 26% (OR 3.3; 1.6-6.5).
      However, at term there were also more subtle differences in weight deficit, with
      more fetuses with a weight between the 10th and 50th centiles than between 50th
      and 90th (36 vs 11; OR 3.3; 1.4-7.8). Mothers of pregnancies ending in stillbirth
      were similar in age, size, parity and ethnic group to mothers of live born
      babies, but were more likely to be smokers (37 vs 27%, OR 1.6; 1.2-2.3).
      CONCLUSIONS: Many stillborn babies are small for gestational age. In the absence
      of significant differences in physiological pregnancy characteristics, this is
      unlikely to be a constitutional smallness, but represents a preponderance of
      intrauterine growth restriction. For a full appreciation of the strength of this
      association, appropriate weight standards and classifications need to be applied
      in perinatal mortality surveys. Many antepartum stillbirths which are currently
      designated as unexplained may be avoidable if slow fetal growth could be
      recognised as a warning sign.

PMID- 9637123
TI  - Application of a customised birthweight standard in the assessment of perinatal
      outcome in a high risk population.
AB  - OBJECTIVE: Physiological as well as pathological variables influence birthweight.
      The aim of the present study was to examine perinatal outcome in relation to
      birthweight centiles applying a customised birthweight standard. METHODS: Two
      hundred and seventeen babies from high risk pregnancies were evaluated and
      classified as small or not small for gestational age according to two standards:
      1. conventional Dutch birthweight centiles and 2. customised centiles which
      adjust individually for physiological variables like maternal booking weight,
      height and ethnic origin. RESULTS: Customisation of the weight standards resulted
      in identification of an additional group of infants who were small for
      gestational age, but not by the Dutch standards. These babies were associated
      with significantly more adverse perinatal events than those who were not small
      for gestational age as defined by a customised standard. CONCLUSIONS: Adjustment
      of birthweight centiles for physiological variables significantly improves the
      identification of infants who have failed to reach the expected birthweight and
      who are at increased risk for adverse perinatal events.

PMID- 9637124
TI  - Fetal growth velocity in the prediction of intrauterine growth retardation in a
      low risk population.
AB  - OBJECTIVE: To determine whether fetal growth velocity derived from two antenatal
      ultrasound measurements in the third trimester, 28 days apart, can identify
      infants born with anthropometric features of intrauterine growth retardation.
      DESIGN: Prospective observational study. SETTING: Department of obstetric
      ultrasound, Ninewells Hospital, Dundee. SUBJECTS: Two hundred and seventy four
      low risk women participating in a longitudinal study of serial fortnightly
      ultrasound in pregnancy. METHODS: Growth velocities of the fetal abdominal area
      and bi-parietal diameter were calculated from the third from last and last
      measurements prior to delivery. Receiver Operator Characteristics curves were
      employed to determine an optimal cutoff point for velocity to predict
      intrauterine malnourishment. MAIN OUTCOME MEASURES: Likelihood ratios for fetal
      abdominal area and bi-parietal diameter growth velocity in the prediction of
      growth retarded infants with skinfold thickness < 10th centile; ponderal index <
      25th centile, or mid-arm circumference to occipito-frontal circumference ratio
      (MAC:OFC ratio) of less than -1 SD. A likelihood ratio of > 10 generates
      significant changes in the pre-test probability of growth retardation, whereas a
      likelihood ratio of 5 to 10 generates only moderate changes. RESULTS: Fetal
      abdominal area velocity predicted growth retardation with likelihood ratio 10.4
      (95% CI 3.9 to 26) for skinfold thickness; likelihood ratio 9.5 (95% CI 4.6 to
      19) for ponderal index; a likelihood ratio 4.7 (2.3 to 8.4) for MAC:OFC. Bi
      parietal diameter velocity predicted growth retardation with likelihood ratio 6.5
      (95% CI 1.9 to 20) for skinfold thickness but did not predict low ponderal index
      or MAC:OFC ratio. CONCLUSIONS: Fetal abdominal area velocity is useful in
      identifying infants with reduced skinfold thickness or low ponderal index.
      Prospective evaluation of serial ultrasound and velocity calculation in a
      selected population at increased risk of growth failure and a clearer
      understanding of the relative significance of the different neonatal
      anthropometric measures of impaired growth achievement is necessary before the
      estimation of growth velocity can be recommended in clinical practice.

PMID- 9637125
TI  - Optimising maternal-fetal outcomes in preterm labour: a decision analysis.
AB  - OBJECTIVE: To compare, using decision analytic techniques, maternal and fetal
      risk and benefits of three strategies for the management of preterm labour after
      32 weeks. These strategies are empiric tocolysis, no tocolysis, or amniocentesis
      for fetal maturity testing. DATA SOURCES: Published medical literature provided
      the probabilities, including those for tocolysis efficacy, maternal and neonatal
      outcomes, and steroid efficacy. DATA: Synthesis Separate decision trees were
      created for hypothetical cohorts of patients presenting with preterm labour at
      32, 34, and 36 weeks of gestation to compare strategies. The primary outcome was
      the total number of expected adverse maternal and neonatal events for each
      strategy at each gestational age. RESULTS: At 32 weeks tocolysis yielded the
      lowest total number of adverse maternal and neonatal events. At 34 weeks, both
      tocolysis and no tocolysis yielded similar overall outcomes. At 36 weeks most
      clinical outcomes were good regardless of strategy. CONCLUSIONS: This analysis
      supports the empiric use of tocolytics at 32 weeks. At 34 weeks, either tocolysis
      or no tocolysis appear to be reasonable alternatives. At 36 weeks no tocolysis is
      probably preferred. This analysis also suggests that amniocentesis should not be
      employed in the management of preterm labour at these gestational ages.

PMID- 9637126
TI  - Antenatal corticosteroid therapy and risk of osteoporosis.
AB  - OBJECTIVE: To assess the risk of maternal osteoporosis associated with antenatal
      corticosteroid administration for neonatal respiratory distress syndrome
      prophylaxis. DESIGN: Prospective longitudinal study. SETTING: Maternity unit of
      Chelsea and Westminster Hospital, London. POPULATION: Fourteen pregnant women who
      received dexamethasone therapy for fetal lung maturation in anticipation of
      delivery before 34 completed weeks of gestation. METHODS: Blood samples were
      collected before dexamethasone administration, 24 hours and 48 hours after the
      course of dexamethasone, and within 24 hours of delivery. Serum levels of carboxy
      terminal pro-peptide of type I pro-collagen (PICP) were measured to monitor the
      rate of bone formation, and serum levels of cross-linked carboxy terminal
      telopeptide (ICTP) were measured as a marker of bone resorption. MAIN OUTCOME
      MEASURES: Changes in the markers of bone turnover following dexamethasone
      administration. RESULTS: Serum PICP levels dropped 24 hours after dexamethasone
      therapy (P = 0.001), but partially recovered by 48 hours (P = 0.014) to reach
      higher than pre-therapy levels at delivery (P = 0.044). Although there were no
      corresponding changes in the serum levels of ICTP after 24 and 48 hours of
      therapy, levels increased from pretherapy to delivery (P = 0.006). CONCLUSION:
      Antenatal corticosteroid therapy leads to a transient suppression of, followed by
      an increase in, bone formation without any significant alteration in the pattern
      of bone resorption expected during pregnancy.

PMID- 9637127
TI  - Antenatal glucocorticoid administration increases corticotrophin-releasing
      hormone in maternal plasma.
AB  - OBJECTIVE: This study was designed to determine whether maternal corticotrophin
      releasing hormone (CRH) concentrations are altered after maternal betamethasone
      administration for fetal lung maturity in women with threatened preterm labour
      and whether these effects are dependent on gestational age. METHODS: Our study
      included 49 women with threatened preterm labour who received prenatal
      betamethasone for fetal lung maturity between 24 and 31 weeks of gestational age
      and 11 women who did not. Maternal blood was taken before and after
      glucocorticoid administration or at 24 hours after initial sampling. Plasma CRH,
      adrenocorticotrophin (ACTH) and cortisol concentrations were determined by
      radioimmunoassays. The women were stratified into 24-25 weeks, 26-27 weeks, 28-29
      weeks, and 30-31 weeks completed gestation. RESULTS: At each gestational age,
      maternal cortisol concentrations decreased by approximately 85% after
      glucocorticoid administration. Overall mean cortisol values fell from 580.0 (SD,
      351.8) to 89.7 (96.6) nmol/L (n = 40, P < 0.001). Overall mean ACTH values
      decreased from 9.9 (4.7) to 5.0 (3.4) pmol/L (n = 43, P < 0.001), and the
      approximate 50% decrease was similar at each gestational age. In marked contrast,
      overall mean CRH values increased from 58.0 (37.0) to 87.8 (68.6) pmol/L (n = 49,
      P < 0.001) after betamethasone administration. There was no change in maternal
      cortisol, ACTH or CRH values over 24 hours in women who did not receive
      betamethasone. CONCLUSIONS: We conclude that maternal betamethasone
      administration increases maternal plasma CRH values between 24 and 31 completed
      weeks of gestation.

PMID- 9637128
TI  - Disproportionate fetal growth and fingerprint patterns.
AB  - Fingerprint whorl patterns are formed during fetal life. In a group of 180 term
      infants, those with more fingerprint whorls tended to have a small abdominal
      circumference (P = 0.09) and high ratio of head to abdominal circumference (P =
      0.008). These associations were independent of the relation between the whorl
      counts of the mothers and their infants. We also found an independent correlation
      between the babies' whorl count and the combination of increasing subscapular (P
      = 0.03) and decreasing triceps (P = 0.02) skinfold thicknesses of the mothers.
      Whorl patterns are associated with adult hypertension; maternal nutritional
      status may influence their common origin during fetal development.

PMID- 9637129
TI  - Maternal death due to cerebral toxoplasmosis.

PMID- 9637130
TI  - The disappearance of fetal and donor red blood cells in alloimmunised
      pregnancies: a reappraisal.

PMID- 9637131
TI  - Unsuccessful treatment of missed abortion.

PMID- 9637132
TI  - Menstrual cycle variation in mammographic breast density: so who cares?

PMID- 9637133
TI  - Serum insulin-like growth factor-I levels and prostate cancer risk--interpreting
      the evidence.

PMID- 9637134
TI  - Pathology vs. prognosis: are hereditary cancers a different breed?

PMID- 9637135
TI  - Herceptin raises its sights beyond advanced breast cancer.

PMID- 9637136
TI  - Ashkenazi community is not unwilling to participate in genetic research.

PMID- 9637137
TI  - Lag in colorectal screening rates prompts innovation.

PMID- 9637139
TI  - Variation in mammographic breast density by time in menstrual cycle among women
      aged 40-49 years.
AB  - BACKGROUND: Mammography is less effective for women aged 40-49 years than for
      older women, which has led to a call for research to improve the performance of
      screening mammography for younger women. One factor that may influence the
      performance of mammography is breast density. Younger women have greater
      mammographic breast density on average, and increased breast density increases
      the likelihood of false-negative and false-positive mammograms. We investigated
      whether breast density varies according to time in a woman's menstrual cycle.
      METHODS: Premenopausal women aged 40-49 years who were not on exogenous hormones
      and who had a screening mammogram at a large health maintenance organization
      during 1996 were studied (n = 2591). Time in the menstrual cycle was based on the
      woman's self-reported last menstrual bleeding and usual cycle length. RESULTS: A
      smaller proportion of women had "extremely dense" breasts during the follicular
      phase of their menstrual cycle (24% for week 1 and 23% for week 2) than during
      the luteal phase (28% for both weeks 3 and 4) (two-sided P = .04 for the
      difference in breast density between the phases, adjusted for body mass index).
      The relationship was stronger for women whose body mass index was less than or
      equal to the median (two-sided P<.01), the group who have the greatest breast
      density. CONCLUSIONS/IMPLICATIONS: These findings are consistent with previous
      evidence suggesting that scheduling a woman's mammogram during the follicular
      phase (first and second week) of her menstrual cycle instead of during the luteal
      phase (third and fourth week) may improve the accuracy of mammography for
      premenopausal women in their forties. Breast tissue is less radiographically
      dense in the follicular phase than in the luteal phase.

PMID- 9637140
TI  - Insulin-like growth factor 1 and prostate cancer risk: a population-based, case
      control study.
AB  - BACKGROUND: Recent epidemiologic investigations have suggested an association
      between increased blood levels of insulin-like growth factor 1 (IGF-1) and
      increased risk of prostate cancer. Our goal was to determine whether an
      association exists between serum levels of IGF-1 and one of its binding proteins,
      insulin-like growth factor-binding protein 3 (IGFBP-3), and prostate cancer risk.
      METHODS: An immunoradiometric assay was used to quantify IGF-1 levels and IGFBP-3
      levels in serum samples as part of a population-based, case-control study in
      Sweden. The study population comprised 210 patients with newly diagnosed,
      untreated prostate cancer and 224 frequency-matched control subjects. Data were
      analyzed by use of unconditional logistic regression to calculate odds ratios
      (ORs) and 95% confidence intervals (CIs). Reported P values are two-sided.
      RESULTS: The mean serum IGF-1 level for case patients (158.4 ng/mL) was
      significantly higher than that for control subjects (147.4 ng/mL) (P = .02);
      corresponding mean serum IGFBP-3 levels were not significantly different between
      case patients (2668 ng/mL) and control subjects (2518 ng/mL) (P =.09). We found a
      moderately strong and statistically significant (P = .04) positive association
      between serum levels of IGF-1 levels and risk of prostate cancer (OR = 1.51; 95%
      CI = 1.0-2.26 per 100 ng/mL increment); the association was particularly strong
      for men younger than 70 years of age (OR = 2.93; 95% CI = 1.43-5.97). No
      association was found between serum IGF-1 levels and disease stage. Serum IGFBP-3
      levels were not significantly associated with increased risk of disease, and
      adjustment for IGFBP-3 had little effect on the association between IGF-1 levels
      and risk of prostate cancer. CONCLUSION: Elevated serum IGF-1 levels may be an
      important predictor of risk for prostate cancer. However, our results do not
      support an important role for serum IGFBP-3 as a predictor of risk for this
      disease.

PMID- 9637138
TI  - Photodynamic therapy.
AB  - Photodynamic therapy involves administration of a tumor-localizing
      photosensitizing agent, which may require metabolic synthesis (i.e., a prodrug),
      followed by activation of the agent by light of a specific wavelength. This
      therapy results in a sequence of photochemical and photobiologic processes that
      cause irreversible photodamage to tumor tissues. Results from preclinical and
      clinical studies conducted worldwide over a 25-year period have established
      photodynamic therapy as a useful treatment approach for some cancers. Since 1993,
      regulatory approval for photodynamic therapy involving use of a partially
      purified, commercially available hematoporphyrin derivative compound (Photofrin)
      in patients with early and advanced stage cancer of the lung, digestive tract,
      and genitourinary tract has been obtained in Canada, The Netherlands, France,
      Germany, Japan, and the United States. We have attempted to conduct and present a
      comprehensive review of this rapidly expanding field. Mechanisms of subcellular
      and tumor localization of photosensitizing agents, as well as of molecular,
      cellular, and tumor responses associated with photodynamic therapy, are
      discussed. Technical issues regarding light dosimetry are also considered.

PMID- 9637142
TI  - Exposure to breast milk in infancy and adult breast cancer risk.
AB  - BACKGROUND: There is considerable interest in the possibility of an infectious
      etiology for human breast cancer. Although studies have shown that certain
      strains of mice transmit mammary tumor virus via breast milk, few epidemiologic
      studies have addressed this topic in humans. METHODS: We evaluated the
      relationship between having been breast-fed as an infant and breast cancer risk
      among 8299 women who participated in a population-based, case-control study of
      breast cancer in women aged 50 years or more. Case women were identified through
      cancer registries in three states (Massachusetts, New Hampshire, and Wisconsin);
      control women were identified through statewide driver's license lists (age <65
      years) or Medicare lists (ages 65-79 years). Information on epidemiologic risk
      factors was obtained through telephone interview. We used multiple logistic
      regression to assess having been breast-fed and maternal history of breast cancer
      in relation to breast cancer occurrence both in premenopausal women (205 case
      women; 220 control women) and in postmenopausal women (3803 case women; 4071
      control women). RESULTS: We found no evidence that having been breast-fed
      increased breast cancer risk in either premenopausal women (odds ratio [OR] =
      0.65; 95% confidence interval [CI] = 0.41-1.04) or postmenopausal women (OR =
      0.95; 95% CI = 0.85-1.07). In addition, breast cancer risk was not increased by
      having been breast-fed by a mother who later developed breast cancer. CONCLUSION:
      Our results do not support the hypothesis that a transmissible agent in breast
      milk increases breast cancer risk. Because premenopausal women were not well
      represented in our study population, our findings with regard to this group may
      not be generalizable and should be viewed with caution.

PMID- 9637141
TI  - Association of p27Kip1 levels with recurrence and survival in patients with stage
      C prostate carcinoma.
AB  - BACKGROUND: There are few biologic determinants that are prognostic for patients
      with localized prostate cancer. We examined whether cellular levels of the cyclin
      kinase inhibitor p27Kip1 (also known as p27) in prostate tumors could be used to
      predict progression of this disease. METHODS: Levels of p27 in tumor cell nuclei
      were assessed by immunohistochemical analysis of tissue sections from the primary
      tumors of 96 patients with stage C prostate carcinoma who had been treated by
      radical prostatectomy. Tumors were classified into one of the following three
      groups on the basis of the percentage of tumor cells showing nuclear p27
      reactivity: low (0%-10%), moderate (11%-50%), and high (>50%). The Mantel
      Haenszel test, Kaplan-Meier analysis, and the logrank test were used to calculate
      the probability that nuclear p27 levels were associated with tumor grade and
      substage, with a serum prostate-specific antigen (PSA) recurrence (defined as the
      finding of a detectable level [0.4 ng/mL or greater] of serum PSA following
      radical prostatectomy), with the recurrence of clinically evident disease, and
      with survival. All reported P values are two-sided. RESULTS: Luminal cells and
      basal cells of normal prostate glands showed high levels of nuclear p27
      immunoreactivity in all tissue sections examined. Fifty-three tumors showed high
      p27 reactivity, 31 showed moderate reactivity, and 12 showed low or no detectable
      reactivity. Decreased levels of p27 were associated with tumor grade (P = .004).
      Tumor levels of p27 were not associated with preoperative prostate-specific
      antigen levels (P = .360) or with tumor substage (P = .320). However, decreased
      p27 reactivity was significantly associated with an increased probability of
      recurrence (P = .004) and decreased survival (P = .010). The median recurrence
      free interval for patients with tumors showing high, moderate, or low p27
      reactivity was 13.7 years, 8.4 years, and 4.7 years, respectively. Median
      survival times were more than 14 years, more than 13.5 years, and 8.1 years for
      patients in the high, moderate, and low p27 reactivity groups, respectively.
      CONCLUSION: Levels of nuclear p27 immunoreactivity in the primary tumor can be
      used to predict recurrence and survival among patients with localized prostate
      cancer.

PMID- 9637143
TI  - Short-term effects of population-based screening for prostate cancer on health
      related quality of life.
AB  - BACKGROUND: Population-based screening for prostate cancer is currently being
      evaluated in randomized clinical trials in the United States and in Europe. Side
      effects arising from the process of screening and from the earlier treatment of
      screen-detected prostate cancer may be important factors in the evaluation. To
      examine health-related quality of life (or health status) among men screened for
      prostate cancer, we conducted a longitudinal study of 626 attenders to the
      Rotterdam (The Netherlands) prostate cancer screening program and of 500
      nonparticipants. METHODS: Attenders of the screening program and nonparticipants
      completed self-assessment questionnaires (SF-36 [i.e., Medical Outcomes Study 36
      Item Short-Form Health Survey] and EQ-5D [i.e., EuroQol measure for health
      related quality of life] health surveys) to measure generic health status, as
      well as an additional questionnaire for anxiety and items relating to prostate
      cancer screening. RESULTS: Physical discomfort during digital rectal examination
      and during transrectal ultrasound was reported by 181 (37%) of 491 men and by 139
      (29%) of 487 men, respectively; discomfort during prostate biopsy was reported by
      64 (55%) of 116 men. Mean scores for health status and anxiety indicated that the
      participants did not experience relevant changes in physical, psychological, and
      social functioning during the screening procedure. However, high levels of
      anxiety were observed throughout the screening process among men with a high
      predisposition to anxiety. Similar scores for anxiety predisposition were
      observed among attenders and nonparticipants. CONCLUSIONS: At the group level, we
      did not find evidence that prostate cancer screening induced important short-term
      health-status effects, despite the short-lasting side effects related to the
      biopsy procedure. However, subgroups may experience high levels of anxiety. The
      implication is that unfavorable health-status effects of prostate cancer
      screening occur mainly in the treatment phase.

PMID- 9637144
TI  - Re: Long-term feeding of sodium saccharin to nonhuman primates: implications for
      urinary tract cancer.

PMID- 9637145
TI  - Blood supply of metastatic hepatic tumors: suggestions for improved delivery of
      chemotherapeutic agents.

PMID- 9637146
TI  - Re: Alcohol dehydrogenase 3 genotype and risk of oral cavity and pharyngeal
      cancers.

PMID- 9637147
TI  - Re: A National Cancer Institute Workshop on Hereditary Nonpolyposis Colorectal
      Cancer Syndrome: meeting highlights and Bethesda Guidelines.

PMID- 9637148
TI  - Practice management guidelines for trauma from the Eastern Association for the
      Surgery of Trauma.

PMID- 9637149
TI  - Neurogenic hypotension in patients with severe head injuries.
AB  - OBJECTIVE: To examine the occurrence of hypotensive episodes in patients with
      severe traumatic brain injuries that are not of hypovolemic origin and to
      investigate possible neurogenic or iatrogenic causes of such episodes. METHODS:
      We reviewed Traumatic Coma Data Bank (TCDB) records of the 248 patients with
      early hypotension. We attempted to eliminate episodes related to hemorrhagic
      hypovolemia by excluding patients with (1) extracranial injuries of Abbreviated
      Injury Scale scores > 3 (n = 99, 40%); (2) postresuscitation hematocrit levels <
      35% (n = 76, 30.6%); (3) hematocrit levels decreasing to < 35% during the first
      24 hours after injury (n = 47, 19%); and (4) patients with conflicting data (n =
      5, 2%). This left 21 patients (8.5%) without discernible extracranial causes for
      their hypotension. RESULTS: Of these 21 patients, 4 had no extracranial injuries
      and 4 had only a single injury with Abbreviated Injury Scale score = 1.
      Hypotensive episodes were not associated with terminal or unsalvageable status.
      Mortality was 43%. Of the multiple factors investigated, the only two that were
      strongly associated with these "unexplained" hypotensive episodes were the
      presence of a diffuse injury pattern on computed tomography (n = 15, 71%) and the
      early use of mannitol or furosemide (n = 16, 76%) (It was policy at TCDB centers
      that hypotensive patients not receive diuretics until they were resuscitated.)
      CONCLUSIONS: (1) Some episodes of severe traumatic brain injury-related
      hypotension may be of neurogenic origin. (2) The risk/benefit ratio of early
      diuretic use in patients with severe traumatic brain injuries may be too high to
      support liberal use. These data strongly support the need for a study involving
      prospective collection of data describing the early blood pressure courses in
      such patients.

PMID- 9637150
TI  - A biomechanical strength comparison of external fixators.
AB  - BACKGROUND: The purpose of this study was to biomechanically test the current
      commercially available uniplanar, half-pin external fixators, comparing
      stiffness, weight, and cost. METHODS: The Hammer, HexFix, Hoffmann, Monotube
      Blue, Monotube Red, Torus, TraumaFix, and Ultra-X were tested using previously
      published methods. The Instron 4500 was used to assess the strength
      characteristics in axial, torsional, anteroposterior, and lateral bending of each
      device. Weight was based on the unassembled fixator construct. Cost was
      determined from the purchase price of each individual fixator. RESULTS: The
      results of this study revealed that the Torus was the stiffest external fixator
      tested in torsion. The Monotube Red was the stiffest in axial loading,
      anteroposterior bending, and lateral bending. The Hammer and Hoffmann external
      fixators were the heaviest constructs. The Torus and HexFix were the most
      expensive. CONCLUSION: Many factors, including stiffness, weight, cost, ease of
      application, fracture characteristics, and personal preference, go into deciding
      which external fixator to use. The data presented compare stiffness
      characteristics of several fixators under standardized loading conditions. These
      data indicate that the Torus and Monotube Red provide the greatest stiffness when
      comparing all modes of failure.

PMID- 9637151
TI  - Long-term results of the external fixation of distal radius fractures.
AB  - OBJECTIVE: To evaluate the long-term results of external fixation of distal
      radius fractures. METHODS: A retrospective follow-up study (median follow-up, 5.3
      years) of 49 patients with 50 distal radius fractures treated with an external
      fixator was carried out. An external fixator (Minifixator, Stratec Medical,
      Waldenburg, Switzerland) was used. The operative procedure is described in
      detail. A personal evaluation including clinical and radiologic assessment of
      both wrists was performed. RESULTS: The functional results, including the
      parameters strength, daily activities, range of motion, and presence of pain, as
      well as an anatomic score, the presence of osteoarthritis, the quality of
      reduction, and complications were recorded. Functional and anatomic results
      indicated excellent to good ratings in more than 80% of the cases. CONCLUSION:
      The external fixator is a versatile tool in the treatment of intra-articular and
      extra-articular fractures of the distal radius. The rate of algodystrophy (reflex
      sympathetic dystrophy) was 6%, and wrist stiffness was not found in our series.

PMID- 9637152
TI  - Timing fracture repair in patients with severe brain injury (Glasgow Coma Scale
      score <9)
AB  - BACKGROUND: Trauma patients with severe brain injury are at risk of secondary
      brain injury. Femur fractures, if present, should be repaired when potential
      causes of secondary brain injury have been corrected. METHODS: Sixty-one patients
      with severe or moderate closed head injury and femur fractures were identified.
      Patients were divided into groups by time until femur fracture reduction.
      RESULTS: An inversely proportional trend was demonstrated when comparing time
      until surgery with the percentage of patients who experienced hypotensive events
      during surgery. Patients in the 0- to 2-hour group were eight times more likely
      to become hypotensive during femur repair than patients in the >24-hour group.
      Seventy-four percent of patients with intracranial pressure monitoring
      experienced cerebral perfusion pressure <70 mm Hg. CONCLUSIONS: Operation in
      similar patients should be done when risks are minimized by adequate
      resuscitation. Secondary brain injury is more common in early femur repair.
      Operation delay of 24 hours may be necessary to prevent hypoxia, hypotension, and
      low cerebral perfusion pressure.

PMID- 9637153
TI  - Emergency craniotomy in a rural Level III trauma center.
AB  - Patients with closed head injury and expanding epidural (EDH) or subdural (SDH)
      hematoma require urgent craniotomy for decompression and control of hemorrhage.
      In remote areas where neurosurgeons are not available, trauma surgeons may
      occasionally need to intervene to avert progressive neurologic injury and death.
      In 1990, a young man with rapidly deteriorating neurologic signs underwent
      emergency burr hole decompression of a combined EDH/SDH at our hospital, with
      complete recovery. In anticipation of future need, five surgeons at our rural,
      American College of Surgeons-verified Level III trauma center participated in a
      neurosurgeon-directed course in emergency craniotomy. Since January 1, 1991, 792
      patients have been entered into the trauma registry, including 60 with closed
      head injury and Glasgow Coma Scale (GCS) score of 13 or less. All but seven were
      transferred to a regional Level II trauma center, which is a minimum flight time
      of 1 hour each way. All patients with EDH (5) and 2 of 14 with SDH were deemed
      too unstable for transport and underwent burr hole decompression followed by
      immediate transfer. All craniotomies were approved by the consulting neurosurgeon
      and were done for computed tomography-confirmed lesions combined with neurologic
      deterioration as demonstrated by (1) GCS score of 8 or less, (2) lateralizing
      signs (dilated pupil, hemiparesis), or (3) development of combined bradycardia
      and hypertension. One patient with a GCS score of 3 on arrival died. Seven
      survivors (mean follow-up, 3.9 years; range, 1-6.5 years), including the index
      case, function independently, although one survivor has moderate cognitive and
      motor impairment. We conclude that early craniotomy for expanding epidural and
      subdural hematomas by properly trained surgeons may save lives and reduce
      morbidity in properly selected cases when timely access to a neurosurgeon is not
      possible.

PMID- 9637154
TI  - New diagnostic peritoneal lavage criteria for diagnosis of intestinal injury.
AB  - BACKGROUND: Although diagnostic peritoneal lavage (DPL) is a well-established,
      reliably objective method of diagnosis of intraperitoneal injury, it is too
      sensitive to be used as an indicator for emergency celiotomy. Therefore, since
      the development of ultrasonography and advanced computed tomographic scanners,
      the role of DPL has been markedly reduced. Despite such remarkable advances,
      however, radiologic diagnosis of intestinal injury cannot always provide
      definitive results, and DPL may still be valuable in such instances. We have
      developed a new DPL criteria specifically designed to aid in the diagnosis of
      intestinal injury and have evaluated its effectiveness. METHODS: From August 1988
      to December 1995, we performed DPL in 250 patients with blunt abdominal trauma
      and analyzed the diagnostic accuracy of our new criteria. We used the standard
      quantitative white blood cell (WBC) criterion for detection of intestinal injury
      supplemented by a positive-negative borderline adjusted to WBC > or = red blood
      cell (RBC)/150, where RBC > or = 10 x 10(4)/mm3. RESULTS: Our criteria had a
      diagnostic sensitivity of 96.6% and a specificity of 99.4% for intestinal injury
      after exclusion of 57 patients in whom DPL was performed within 3 hours or after
      18 hours from the time of injury. In 133 patients with hemoperitoneum, emergency
      celiotomy was performed in only 48; the remaining 85 patients with negative DPL
      based on the WBC criterion avoided surgery, and conservative management resulted
      in no complications. CONCLUSION: With the proposed criteria, DPL can be used to
      diagnose or exclude intestinal injury even in the presence of hemoperitoneum.

PMID- 9637155
TI  - Prospective evaluation of early missed injuries and the role of tertiary trauma
      survey.
AB  - BACKGROUND: This study prospectively evaluated the prevalence, clinical
      significance, and contributing factors to early missed injuries and the role of
      tertiary survey in minimizing frequency of missed injuries in admitted trauma
      patients. Missed injury, clinically significant missed injury, tertiary survey,
      and contributing factors were defined. Tertiary survey was conducted within 24
      hours. RESULTS: Of 206 patients, 134 patients (65%) had 309 missed injuries
      composing 39% of all 798 injuries seen. Tertiary trauma survey detected 56% of
      early missed injuries and 90% of clinically significant missed injuries within 24
      hours. Clinically significant missed injuries occurred in 30 patients with
      complications in 11 patients and death in two patients. Of 224 contributing
      errors, 123 errors were in clinical assessment, 83 errors were in radiology, 14
      errors were patient related, and four errors were technical. The missed injury
      rate was significantly higher in patients with multiple injuries and in those
      involved in road crashes. CONCLUSIONS: Secondary trauma survey is not a
      definitive assessment and should be supplemented by tertiary trauma survey.

PMID- 9637156
TI  - Improved success in nonoperative management of blunt splenic injuries:
      embolization of splenic artery pseudoaneurysms.
AB  - OBJECTIVES: By using abdominal computed tomographic scans in the evaluation of
      blunt splenic trauma, we previously identified the presence of vascular blush as
      a predictor of failure, with a failure of nonoperative management of 13% in that
      series. This finding led to an alteration in our management scheme, which now
      includes the aggressive identification and embolization of splenic artery
      pseudoaneurysms. METHODS: The medical records of 524 consecutive patients with
      blunt splenic injury managed over a 4.5-year period were reviewed for the
      following information: age, Injury Severity Score (ISS), American Association for
      the Surgery of Trauma splenic injury grade (SIG), method and outcome of
      management. RESULTS: Of the patients, 66% were male with a mean age of 32 +/- 16,
      and mean ISS of 25 +/- 13. A total of 180 patients (34%) were managed with urgent
      operation on admission (81% splenectomy (SIG 4.0), 19% splenorrhaphy (SIG 2.6)).
      The remaining 344 patients (66%) were hemodynamically stable and underwent
      computed tomographic scan and planned nonoperative management. Of these patients,
      322 patients (94%) were successfully managed nonoperatively (61% of total splenic
      injuries). In 26 patients (8%), a contrast blush identified on computed
      tomographic scan was confirmed as a parenchymal pseudoaneurysm on arteriography.
      Twenty patients (SIG, 2.8) were successfully embolized. In six patients,
      technical failure precluded embolization; all required splenectomy (SIG, 4.0). A
      total of 22 patients (6%) failed nonoperative management, including the six with
      unsuccessful embolization attempts. Sixteen patients (SIG, 3.0) who had no
      evidence of pseudoaneurysm were explored for a falling hematocrit, hemodynamic
      instability, or a worsening follow-up computed tomography: 13 patients had
      splenectomy, and three patients had splenorrhaphy. CONCLUSIONS: Aggressive
      surveillance for and embolization of posttraumatic splenic artery pseudoaneurysms
      improved the rate of successful nonoperative management of blunt splenic trauma
      to 61%, with a nonoperative failure rate of only 6%. In comparison with our
      previous work, this reduction in failure of nonoperative management is a
      significant improvement (p < 0.03).

PMID- 9637157
TI  - Intra-abdominal hypertension after life-threatening penetrating abdominal trauma:
      prophylaxis, incidence, and clinical relevance to gastric mucosal pH and
      abdominal compartment syndrome.
AB  - OBJECTIVE: To define the incidence, prophylaxis, and treatment of intra-abdominal
      hypertension (IAH) and its relevance to gut mucosal pH (pHi), multiorgan
      dysfunction syndrome, and the abdominal compartment syndrome (ACS). METHODS:
      Seventy patients in the SICU at a Level I trauma center (1992-1996) with life
      threatening penetrating abdominal trauma had intra-abdominal pressure estimated
      by bladder pressure. pHi was measured by gastric tonometry every 4 to 6 hours.
      IAH (intra-abdominal pressure> 25 cm of H2O) was treated by bedside or operating
      room laparotomy. RESULTS: Injury severity was comparable between patients who had
      mesh closure as prophylaxis for IAH (n = 45) and those who had fascial suture (n
      = 25). IAH was seen in 10 (22.2%) in the mesh group versus 13 (52%) in the
      fascial suture group (p = 0.012) for an overall incidence of 32.9%. Forty-two
      patients had pHi monitoring, and 11 of them had IAH. Of the 11 patients, eight
      patients (72.7%) had acidotic pHi (7.10 +/- 0.2) with IAH without exhibiting the
      classic signs of ACS. The pHi improved after abdominal decompression in six and
      none developed ACS. Only two patients with IAH and low pHi went on to develop
      ACS, despite abdominal decompression. Multiorgan dysfunction syndrome points and
      death were less in patients without IAH than those with IAH and in patients who
      had mesh closure. CONCLUSIONS: IAH is frequent after major abdominal trauma. It
      may cause gut mucosal acidosis at lower bladder pressures, long before the onset
      of clinical ACS. Uncorrected, it may lead to splanchnic hypoperfusion, ACS,
      distant organ failure, and death. Prophylactic mesh closure of the abdomen may
      facilitate the prevention and bedside treatment of IAH and reduce these
      complications.

PMID- 9637158
TI  - Alternatives in the management of penetrating injuries to the iliac vessels.
AB  - BACKGROUND: The high mortality and morbidity rates after iliac vessel injuries
      remain a challenging problem for trauma surgeons. Several controversial issues
      surround the management of iliac vessel injuries, including the value of
      abbreviated laparotomy, the role of extra-anatomic bypass reconstruction (EABR),
      the use of vascular prostheses in the presence of contamination, and the need and
      timing for fasciotomy. METHODS: Retrospective review of the records of patients
      who sustained an injury to the iliac vessel between 1987 and 1996. RESULTS: A
      total of 64 patients were treated, including 23 with isolated iliac vein
      injuries, 17 with arterial injuries, and 24 with combined arteriovenous injuries.
      Vascular prostheses were placed in 17 patients with arterial injuries, including
      12 with associated intestinal wounds. Graft infection did not occur. Of the 24
      patients with combined injuries, 11 underwent abbreviated laparotomy and 1 died.
      Five deaths, however, occurred in 13 patients in whom no attempts were made for
      damage control laparotomy. Significant differences between survivors and
      nonsurvivors included final arterial pH, final prothrombin time, length of
      hypotension, and number of transfusions. Arterial ligation with EABR was
      performed in five patients and failed in two. Deep venous thrombosis and
      pulmonary embolism occurred in four patients, in three of them after venous
      injuries were ligated. The overall mortality rate was 23%. CONCLUSION: Our
      findings show that (1) abbreviated laparotomy reduces mortality in iliac
      injuries; (2) EABR should be performed early after stabilization to prevent limb
      ischemia; (3) the use of vascular prostheses with associated intestinal injuries
      did not appear to increase the incidence of graft infection; and (4) after vein
      ligation, early fasciotomy and prophylaxis against extremity swelling, deep
      venous thrombosis, and pulmonary embolism should be considered.

PMID- 9637159
TI  - Intestinal permeability correlates with severity of injury in trauma patients.
AB  - BACKGROUND: Increased intestinal permeability (IP) and the release of toxic
      intraluminal materials have been implicated in the systemic inflammatory response
      syndrome (SIRS) and multiple organ failure (MOF) observed in patients after
      severe trauma. Previous studies of intestinal permeability have failed to
      demonstrate a correlation between early measurements of IP and indicators of
      injury severity. This study examines the relationship between standard measures
      of injury severity and the early (day 1) and delayed (day 4) changes in IP.
      Associations between IP and the development of SIRS, MOF, and infectious
      complications were also studied. METHODS: The metabolically inactive markers
      lactulose (L) and mannitol (M) were used to measure IP in 29 consecutive patients
      who sustained injuries that required admission to the surgical intensive care
      unit and in 10 healthy control subjects. Measurements were made within 24 hours
      of admission and on hospital day 4. Severity of injury was assessed by A Severity
      Characterization of Trauma (ASCOT), Trauma and Injury Severity Score (TRISS),
      Injury Severity Score (ISS), Revised Trauma Score (RTS), and Acute Physiology and
      Chronic Health Evaluation (APACHE) II score. Postinjury infections and parameters
      of SIRS and MOF were recorded. RESULTS: The IP of healthy volunteers (L/M, 0.025
      +/- 0.008) was within the normal range (L/M < or = 0.03), whereas the average IP
      in injured patients was increased both within 24 hours (L/M, 0.139 +/- 0.172) and
      on the fourth hospital day (L/M, 0.346 +/- 0.699). No significant correlation
      between severity of injury and increased IP was seen within 24 hours of injury. A
      significant correlation was seen on hospital day 4, however, with all severity
      indices measured (ASCOT: r = 0.93, R2 = 0.87, p < 0.001; TRISS: r = 0.93, R2 =
      0.87, p < 0.001; ISS: r = 0.84, R2 = 0.70, p < 0.001; RTS: r = 0.68, R2 = 0.47, p
      = 0.002; APACHE II score: r = 0.51, R2 = 0.26, p = 0.04). Patients with markedly
      increased IP (L/M > or = 0.100) experienced a significant increase in the
      development of SIRS (83 vs. 44%; p = 0.03) and subsequent infectious
      complications (58 vs. 13%; p = 0.01) and showed close correlation with the
      multiple organ dysfunction scores (r = 0.87, R2 = 0.76, p < 0.001). CONCLUSION:
      These observations demonstrate that the increased IP observed after trauma
      correlates with severity of injury only after 72 to 96 hours and not within the
      initial 24 hours of injury. A large increase in IP is associated with the
      development of SIRS, multiple organ dysfunction, and an increased incidence of
      infectious complications.

PMID- 9637160
TI  - Both T-helper-1- and T-helper-2-type lymphokines are depressed in posttrauma
      anergy.
AB  - BACKGROUND: We have previously shown that an intrinsic postinjury T-cell
      dysfunction defined as lack of proliferative response to direct stimulation
      through the T-cell receptor, referred to here as "anergy," occurs in a subgroup
      of patients with severe trauma and is associated with organ failure. It has been
      suggested recently that a dominance of T-helper-2 (Th2) lymphokine production
      might be responsible for immunosuppression and associated with poor patient
      outcome. Here, we hypothesize that anergy is associated with global failure of T
      lymphokine (T LK) production, suggesting that poor outcome is not the result of
      an excess of immunosuppressive T LK (i.e., interleukin (IL)-10) but rather
      results from lost T-cell regulatory networking. METHODS: Purified T cells from 37
      severely injured trauma patients were cultured and stimulated with
      alphaCD3/alphaCD4, and proliferation was assessed at 72 hours. Anergy is defined
      as occurring when the patient's T-cell proliferation to alphaCD3/alphaCD4 is less
      than 50% of the simultaneously run normal proliferation. Culture supernatants
      were assessed for T LK production by enzyme-linked immunosorbent assay. Clinical
      severity was measured by the multiple organ dysfunction syndrome (MODS) and Acute
      Physiology and Chronic Health Evaluation III scores. RESULTS: Anergy occurred in
      20 of 37 patients, and it usually appeared at greater than 5 to 7 days after
      injury. There was a global reduction of T LK production during T-cell anergy (IL
      2, 2.5%; interferon (IFN)gamma, 30.5%; IL-4, 11.8%; and IL-10, 16.9%) compared
      with increased or unchanged T LK production during the nonanergic state (IL-2,
      83%; IFNgamma, 230%; IL-4, 110%; and IL-10, 307.9%; p < 0.01). There was a
      significant direct correlation between depressed IL-4 and depressed IFNgamma (r =
      0.620, p < 0.001), indicating a diminished LK production of both types of T
      helper cells (Th1 and Th2). Decreased IL-2 and IL-10 levels were also
      specifically correlated to each other during the anergic state (r = 0.91, p <
      0.001). The average MODS score for patients during anergy was significantly
      higher (7.6) than their MODS score in the absence of anergy (4.0, p = 0.01). When
      IL-2 and IL-10 were measured simultaneously, a predominance of Th2 LK (IL-10)
      production would result in an IL-10/IL-2 ratio greater than 1. We found, however,
      that this ratio was not greater than 1 in 80% of assays in which T cells were
      anergic (p = 0.01). CONCLUSION: During T-cell anergy there is not a predominance
      of Th2 lymphokine production but rather a global depression of the T-cell
      lymphokine profile. Both depressed T-cell proliferation and depressed LK
      production correlate to poor clinical outcome.

PMID- 9637161
TI  - Recombinant human granulocyte colony-stimulating factor attenuates inflammatory
      responses in septic patients with neutropenia.
AB  - OBJECTIVE: The objective of this study was to determine the effects of
      recombinant human granulocyte colony-stimulating factor (rhG-CSF) administration
      in septic patients with neutropenia. METHODS: Twenty consecutive septic patients
      were administered rhG-CSF subcutaneously (2 microg x kg(-1) x d(-1)) for 5 days
      (group G). They were compared with 14 septic patients treated earlier without rhG
      CSF (group N). All patients in both groups met the criteria of total leukocyte
      count (TLC) less than 5,000/mm3 and C-reactive protein (CRP) more than 10 mg/dL.
      Changes in TLC, absolute neutrophil count (ANC), CRP, respiratory index (RI),
      Acute Physiology and Chronic Health Evaluation (APACHE) II score, and Goris's
      Multiple Organ Failure (MOF) index were evaluated. In addition, nucleated cell
      count (NCC), differentiation in bone marrow aspiration, neutrophil phagocytic and
      bactericidal activity, serum concentrations of interleukin-6 (IL-6) and IL-8 as
      inflammatory markers, and plasma concentration of leukocyte elastase (LE) as an
      indicator of the tissue injury were evaluated in group G. RESULTS: In group G,
      TLC, ANC, NCC, and neutrophil functions increased significantly, whereas CRP, IL
      6, and IL-8 decreased reciprocally. There was no deterioration of LE and RI.
      Consequently, the APACHE II score and MOF index improved. In group N, however,
      CRP showed no change concomitant with the APACHE II score and MOF index.
      CONCLUSION: Administration of rhG-CSF attenuates inflammatory responses without
      inducing tissue injury in septic patients with neutropenia.

PMID- 9637162
TI  - Changes of the interleukin-6 levels in skin at different sites after thermal
      injury.
AB  - OBJECTIVE: To delineate the regulation of IL-6 production in unburned skin
      adjacent to a burn in an animal model. METHODS: In C57BL/6 mice, at 15, 30, and
      60 minutes after a 20% full-thickness burn, skin was removed from various sites.
      Control samples were obtained from unburned mice. Normal skins were incubated
      with tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1alpha), IL
      1 beta, and IL-6. Unburned skin specimens were incubated with anti-TNF-alpha and
      IL-1alpha antibodies. Cytokine levels were measured by enzyme-linked
      immunosorbent assay. RESULTS: The burn increased the IL-6 levels at 30 minutes (p
      < 0.05) and the IL-1alpha levels at 15 and 60 minutes in the unburned skin. TNF
      alpha, IL-1alpha, and IL-1beta increased IL-6 production in normal skin (p <
      0.05). Anti-IL-1alpha antibody decreased IL-6 production in the unburned skin (p
      < 0.05). CONCLUSIONS: IL-1alpha modulates IL-6 production in unburned skin after
      injury. IL-6 and IL-1alpha might contribute to the alterations after a burn.

PMID- 9637163
TI  - Imprecision in lower "inflection point" estimation from static pressure-volume
      curves in patients at risk for acute respiratory distress syndrome.
AB  - BACKGROUND: Static pressure-volume (PV) curves have been promoted as a tool for
      selecting positive end-expiratory pressure (PEEP) by identifying a lower
      "inflection point" (Pflex) from these curves. Their visual interpretation is
      subjective and difficult, however, particularly with subtle changes in the slope
      of the curves. This study was designed to examine the physician-to-physician
      variability in estimating the lower Pflex from these curves. METHODS: Static PV
      curves for eight patients were obtained within 24 hours of admission. Five
      intensivists and one respiratory therapist independently estimated the lower
      Pflex from these curves. RESULTS: Pflex estimates for individual patients were
      highly variable, ranging from 5 to 9 cm H2O. This variability was not
      attributable to a single discordant estimate, nor was a single physician
      responsible for consistently high or low estimates. CONCLUSION: Static PV curve
      interpretation with current methods imprecisely estimates the lower inflection
      point and is of limited usefulness in PEEP selection.

PMID- 9637164
TI  - Significance of peritoneal fluid as an isolated finding on abdominal computed
      tomographic scans in pediatric trauma patients.
AB  - BACKGROUND: Peritoneal fluid on abdominal computed tomographic (CT) scan in the
      absence of solid-organ injury suggests a bowel injury. We sought to determine the
      significance of peritoneal fluid as the sole finding on abdominal CT scans
      obtained to evaluate injured pediatric patients. METHODS: We performed a
      retrospective review of abdominal CT scans obtained during the initial survey of
      blunt trauma patients less than 19 years old during a 5-year period (1991-1995).
      All patients received intravenous and oral contrast agents. All CT scans were
      read by a staff radiologist. All CT scan results were retrospectively verified by
      one of the authors. RESULTS: Of the 259 scans, 157 (59%) were read as normal; 76
      (31%) demonstrated solid-organ injury or pelvic fracture; 2 (1%) had
      pneumoperitoneum and 24 (9%) had peritoneal fluid as the only finding.
      Quantification of the fluid was done using a previously described method. Of the
      16 patients with a small amount of fluid, only 2 (12%) required celiotomy. Of the
      eight patients with a moderate amount of fluid, four (50%) required celiotomy. At
      celiotomy, the six patients all had small-bowel injuries. No abdominal CT scan
      demonstrated extravasation of oral contrast. CONCLUSION: Intra-abdominal fluid as
      the sole finding on abdominal CT scan does not mandate immediate celiotomy in the
      bluntly injured pediatric patient. The patient with fluid in more than one
      location has a 50% chance of bowel injury. We also conclude that extravasated
      enteral contrast is rarely present to aid in the diagnosis of bowel injury in
      children.

PMID- 9637165
TI  - One hundred five penetrating cardiac injuries: a 2-year prospective evaluation.
AB  - OBJECTIVES: To analyze the parameters measured in the field, during transport,
      and upon arrival of the physiologic condition of patients sustaining penetrating
      cardiac injuries, along with the Cardiovascular Respiratory Score (CVRS)
      component of the Trauma Score, the mechanism and anatomical site of injury,
      operative characteristics, and cardiac rhythm as predictors of outcome. We also
      set out to identify a set of patient characteristics that best predict mortality
      outcome and to correlate cardiac injury grade as determined by the American
      Association for the Surgery of Trauma-Organ Injury Scale (AAST-OIS) with
      mortality. METHODS: This report was a prospective study at American College of
      Surgeons Level I urban trauma center. Interventions included thoracotomy,
      sternotomy, or both, for resuscitation and definitive repair of cardiac injury.
      The main outcome measures used were those parameters measuring physiologic
      condition of patients, CVRS, mechanism and anatomical site of injury, mortality,
      and grade of injury. RESULTS: A total of 105 patients sustained penetrating
      cardiac injuries: 68 injuries (65%) were gunshot wounds and 37 injuries (35%)
      were stab wounds. The mean Injury Severity Score was 36. Of the 105 wounds, 23
      wounds (22%) involved multiple-chamber injuries. The overall survival was 35 of
      105 patients (33%): survival of gunshot wound victims was 11 of 68 patients
      (16%); survival of stab wound victims was 24 of 37 patients (65%). Emergency
      department thoracotomy was performed in 71 of the 105 patients (68%) with 10
      survivors (14%). CVRS: 94% mortality (50 of 53) when CVRS = 0, 89% mortality (57
      of 64) when CVRS = 0 to 3, and 31% mortality (12 of 39) when CVRS 4 to 11 (p <
      0.001). The presence of sinus rhythm when pericardium was opened predicted
      survival (p < 0.001). Anatomical site of injury (injured chamber) and the
      presence of tamponade did not predict survival. Stepwise logistic regression
      analysis identified gunshot wound, exsanguination, and restoration of blood
      pressure as most predictive variables of mortality. AAST-OIS injury grade and
      mortality: grade I, 0 of 1 (0%); grade II, 1 of 2 (50%); grade III, 2 of 3 (66%);
      grade IV, 28 of 50 (56%); grade V, 29 of 38 (76%); grade VI, 10 of 11 (91%).
      Overall incidence: grades IV-VI, 99 of 105 (94%). CONCLUSIONS: Parameters
      measuring physiologic condition, CVRS, and mechanism of injury are significant
      predictors of outcome in penetrating cardiac injuries. AAST-OIS injury grades I
      III are rare in penetrating cardiac trauma. AAST-OIS Injury grades IV-VI are
      common in penetrating cardiac trauma and accurately predict outcome.

PMID- 9637166
TI  - Lingual trauma: the use of medicinal leeches in the treatment of massive lingual
      hematoma.

PMID- 9637167
TI  - Esophageal injury secondary to thoracic spinal trauma: the need for early
      diagnosis and aggressive surgical treatment.

PMID- 9637168
TI  - Primary enucleation as a consequence of airbag injury.

PMID- 9637169
TI  - Tension colothorax: a pleural effusion?

PMID- 9637170
TI  - Stent graft of a traumatic vertebral artery injury: case report.

PMID- 9637171
TI  - Bilateral calcaneal fracture in a child treated by percutaneous reduction and
      screw fixation.

PMID- 9637172
TI  - Entrapment and transection of the median nerve associated with greenstick
      fractures of the forearm: case report and review of the literature.
AB  - OBJECTIVE: To report an unusual neurologic complication associated with
      greenstick fractures of the forearm. METHODS: Near-complete transection of the
      median nerve associated with greenstick fractures of the shaft of the left radius
      and ulna in a 13-year-old boy is described. The results of treatment are reported
      in detail. CONCLUSION: Significant median nerve injury may coexist with
      apparently benign, closed greenstick fractures of the forearm.

PMID- 9637173
TI  - Bone transport combined with free flap reconstruction and antibiotic bead spacers
      for a type IIIB open tibial fracture: case report.

PMID- 9637174
TI  - Neurologic dysfunction in the multiple organ dysfunction syndrome.

PMID- 9637175
TI  - A golden opportunity.

PMID- 9637176
TI  - The overall impact of air transport on trauma outcome.

PMID- 9637177
TI  - Closed humeral shaft fractures: a prospective evaluation of surgical treatment.

PMID- 9637178
TI  - Morbidity in 624 patients requiring prehospital chest tube decompression.

PMID- 9637179
TI  - Functional and adaptive significance of primate pads and claws: evidence from New
      World anthropoids.
AB  - This study tests predicted morphoclines in fingertip morphology among four small
      bodied (<1 kg) New World monkeys (Saimiri sciureus, Leontopithecus rosalia,
      Callithrix jacchus, and Saguinus oedipus) in order to test previous functional
      and adaptive explanations for the evolution of flattened nails, expanded apical
      pads, and grasping extremities within the Order Primates. Small-bodied
      platyrrhines which frequently forage among small-diameter substrates are expected
      to possess 1) relatively expanded apical pads, 2) well-developed epidermal
      ridges, 3) distally broad terminal phalanges, and 4) reduced flexor and extensor
      tubercles compared to those species which use large-diameter arboreal supports
      more frequently for their locomotor and postural behaviors. Results show that as
      the frequency of small-branch foraging increases among taxa within this sample,
      relative distal phalanx breadth also increases but distal phalanx length, height,
      and flexor tubercle size decrease. Moreover, epidermal ridge development becomes
      more pronounced as the frequency of small-branch foraging increases. Terminal
      phalanx breadth and epidermal ridge complexity are both positively correlated
      with apical pad size. The large, flexible apical pad increases stability of the
      hand and foot on small-diameter arboreal supports because the pad can contact the
      substrate in several planes which, in turn, enables the pad to resist disruptive
      forces from different directions by friction and interlocking (Hildebrand, 1995).
      The observed morphoclines demonstrate that a gradient in form from claw- to nail
      like tegulae exists among these taxa. Thus, the distinction between claw- and
      nail-bearing platyrrhines is essentially arbitrary. These observations
      corroborate Cartmill's (1972) functional and adaptive model for the loss of claws
      in primates: namely, expanded apical pads are required for habitual locomotor and
      postural behaviors on small-diameter supports whereas claws are more useful for
      positional behaviors on large-diameter substrates. Finally, results from this
      study support previous suggestions that the keeled tegulae of callitrichines
      represent a derived postural adaptation rather than a primitive retention from an
      ancestral eutherian condition.

PMID- 9637180
TI  - Limbic frontal cortex in hominoids: a comparative study of area 13.
AB  - The limbic frontal cortex forms part of the neural substrate responsible for
      emotional reactions to social stimuli. Area 13 is one of the cortical areas long
      known to be part of the posterior orbitofrontal cortex in several monkey species,
      such as the macaque. Its presence nevertheless in the human brain has been
      unclear, and the cortex of the frontal lobe of the great and lesser apes remains
      largely unknown. In this study area 13 was identified in human, chimpanzee,
      bonobo, gorilla, orangutan, and gibbon brains, and cortical maps were generated
      on the basis of its cytoarchitecture. Imaging techniques were used to
      characterize and quantify the microstructural organization of the area, and
      stereological tools were applied for estimates of the volume of area 13 in all
      species. Area 13 is conservative in its structure, and features such as size of
      cortical layers, density of neurons, and space available for connections are
      similar across hominoids with only subtle differences present. In contrast to the
      homogeneity found in its organization, variation is present in the relative size
      of this cortical area (as a percentage of total brain volume). The human and the
      bonobo include a complex orbitofrontal cortex and a relatively smaller area 13.
      On the contrary the orangutan stands out by having a shorter orbitofrontal region
      and a more expanded area 13. Differences in the organization and size of
      individual cortical areas involved in emotional reactions and social behavior can
      be related to behavioral specializations of each hominoid and to the evolution of
      emotions in hominids.

PMID- 9637181
TI  - Second metacarpal midshaft geometry in an historic cemetery sample.
AB  - Study of bone mass at the second metacarpal midshaft has contributed to our
      understanding of skeletal growth and aging within and between populations and has
      relied extensively on noninvasive techniques and in particular radiogrammetric
      data. This study reports age, sex, and side variation in size and shape data
      acquired from direct measurement of cross-sections obtained from a large (n =
      356), homogeneous skeletal sample. Correlation analysis and three-way ANOVA of
      size-adjusted data confirm general impressions of patterned variation in this
      element: males have absolutely but not necessarily relatively larger bones than
      females; the right side is larger than the left, though a larger than expected
      proportion (approximately 25%) of left metacarpals exhibits greater values than
      the right; and bone mass but not strength (in males) declines with age. Contrary
      to the widely accepted assumption of circularity for this location, direct
      measurement of cross-sectional geometry confirms previous biplanar
      radiogrammetric conclusions regarding the noncircularity of the second metacarpal
      midshaft and identifies a significant difference between males and females, with
      the latter having a more cylindrical diaphysis. Deviation of the axes of maximum
      and minimum bending strength associated with noncircularity suggests a
      distribution of bone mass to resist bending moments perpendicular to the distal
      palmar arch, though this conclusion awaits more robust study of the functional
      anatomy of the metacarpal diaphysis.

PMID- 9637182
TI  - Functional dental correlates of food properties in five Malagasy lemur species.
AB  - Biomechanical explanations are fundamental to studies of functional dental
      morphology. Until recently foods were not classified in mechanical categories
      amenable to a rigorous examination of the fundamental physical relationship
      between teeth and foods. Fruit, insect and leaf categories, although descriptive,
      are mechanically heterogeneous. The diets of five Malagasy lemur taxa were
      described in terms of two mechanical properties, hardness and shear strength, in
      an earlier study (Yamashita, 1996b). In the present study, correlations between
      these two physical food properties and second molar tooth features of two lemur
      families are examined. Several relationships are hypothesized: 1) crest length is
      expected to be positively correlated with food shear strength; 2) the radius of
      curvature (r) of cusps is expected to be positively correlated with food
      hardness; and 3) basin area should increase relative to cusp radius as food
      hardness increases, and cusp-to-basin ratios should decrease with increasing food
      hardness. Two additional hypotheses address the debate concerning the relative
      influences of the most frequently eaten foods versus the most stressful foods in
      determining tooth form. The results of the predicted relationships are equivocal.
      1) Crest length is negatively instead of positively correlated with strong foods.
      Crest lengths are correlated with quantities of leaf consumption, which are
      related to leaf shape more than to material composition. 2) As expected, r is
      positively correlated with food hardness and negatively with shear strength, but
      this applies to upper molar cusps only. Lower molar cusps complicate simple
      generalizations of relationships. 3) Hard foods are correlated with a tight fit
      of occluding cusps and basins instead of the expected loose fit. The most
      stressful foods eaten (hardest and strongest) have higher correlations with tooth
      features than the most frequently eaten foods. Several functional complexes can
      be identified. Hard food items are correlated with short cusps in lemurids, tight
      occlusal fit, small trigon and large talonid areas, and deep, acute basins.
      Large, shallow trigons, shallow, unrestricted talonids, and large upper molar
      basins are indicative of a diet of strong foods. These results demonstrate that
      some variation in tooth features is explicable with reference to mechanical
      properties of diet, although the relationships are complex.

PMID- 9637183
TI  - Evolution of the dentition in prehistoric Ohio Valley Native Americans: II.
      Morphology of the deciduous dentition.
AB  - In order to evaluate the microevolutionary dynamics of morphological features of
      the deciduous dentition, I collected data on the variation of 57 features (33
      crown and 24 root) from prehistoric Ohio Valley populations. I sampled a total of
      370 individuals from 26 populations representing a lineage that inhabited the
      middle and upper Ohio valley region from approximately 3000 to 350 BP.
      Evolutionary changes in the frequencies of morphological features of the
      deciduous teeth in this lineage were limited. Over 80% of the features show no
      significant differences among the populations. The relatively few features that
      show consistent differences separate pre- and postmaize agricultural populations.
      I discuss explanations for this change in terms of selection differences or gene
      flow. The general pattern of morphological trait expression in the deciduous
      teeth of this Ohio Valley lineage corresponds to what has been termed the
      Mongoloid dental complex (sinodonty in the permanent teeth). I suggest additional
      features that, with further study, may be added to this morphological complex.

PMID- 9637184
TI  - Dorset and Thule divergence from East Central Asian roots.
AB  - The history of the immigration of East Asians to America during the last glacial
      period remains controversial. In an attempt to add critical data to this problem,
      a large sample of whole teeth derived from Southeast Asian, Mongolian, Thule,
      Western Inuit, and pre-Inca (Huari) people was quantified (N = 4,507 teeth from
      495 individuals; approximately 30 variables per tooth). Multivariate analysis
      helped establish that all Native Americans were likely derived from one ancient,
      extinct population that resided in the region of Mongolia (east Central Asia),
      and that Mongolians and Southeast Asians are two independent groups. A
      controversial and enigmatic Central Canadian Arctic "Thule culture Inuit" group
      on Southampton Island that survived until 1902 was identified as a relic, mainly
      Paleoeskimo Dorset community. Surprisingly, there was little, or no, indication
      of Dorset-to-Thule gene flow. Cumulatively, the data suggest that a small
      population of Paleoindian founders remained resident in Beringia, may have
      blocked further immigration, and were the antecedents to the Thule/Inuit. With
      the confluence of the Arctic and Pacific oceans at the breakup of Beringia, the
      resulting increased availability of marine animal food sources allowed this
      population to increase in size and expand throughout the eastern Arctic.

PMID- 9637185
TI  - Variability in osteon size in recent human populations.
AB  - The possibility of smaller osteons in the cortical bone of Late Pleistocene human
      populations begs the question of how these histological features vary within
      individual skeletons among and between populations. The distributional
      characteristics of total osteon area (On.Ar) and Haversian canal area (H.Ar) are
      explored using data from three samples of historically known individuals: ribs
      and femora from eighteenth-century Huguenots in England (Spitalfields, n = 20),
      ribs and femora from nineteenth-century British settlers in Canada (St. Thomas, n
      = 21), and ribs from twentieth-century South African cadavers (University of Cape
      Town; following curatorial classifications, n = 10 white, 10 black, 10 colored).
      Neither histological variable is normally distributed. About 96% of the random
      variation is within the individual bone sample. There are no significant
      differences between sexes for either variable in any sample, and age has no
      effect in most instances. Femoral osteons are significantly larger than rib
      osteons within individuals and across samples. Haversian canal area is more
      variable than On.Ar, especially in the twentieth-century sample, where within
      sample coefficients of variation are frequently >100%. Using modern centiles
      developed here, some Late Pleistocene long bone samples have On.Ar values below
      the range of modern variation. Because of ribs' smaller cross-sectional areas and
      less broadly ranging values for On.Ar, ribs would provide a preferable site for
      future comparative studies.

PMID- 9637186
TI  - Prehistoric juvenile rheumatoid arthritis in a precontact Louisiana native
      population reconsidered.
AB  - Descriptions of skeletal pathological conditions evident in the prehistoric
      Tchefuncte adolescent 16ST1-14883b are clarified. The basis is reaffirmed for
      assigning to the described pathological conditions a diagnostic perspective of
      juvenile rheumatoid arthritis or juvenile Lyme disease--a disease that mimics
      juvenile rheumatoid arthritis in its arthritic presentation--rather than of
      assigning them as representative of juvenile onset ankylosing spondylitis or
      other juvenile spondyloarthropathies. A hypothesis (Lewis [1994] Am. J. Phys.
      Anthropol. 93:455-475) is restated that 1) the spirochete Borrelia burgdorferi
      was the infectious agent responsible for prevalence of adult rheumatoid arthritis
      in prehistoric southeastern Native American populations, 2) that B. burgdorferi
      is a possible cause of the arthritis evident in individual 16ST1-14883b, and 3)
      that antibodies to B. burgdorferi provided partial immunity to the related
      spirochete Treponema pallidum for the 16ST1 precontact Tchefuncte population from
      Louisiana, protecting them from severe treponemal response. Given the probable
      widespread existence of Ixodid tick vectors for B. burgdorferi in prehistoric
      North America, coupled with the existence of treponematosis, it follows that the
      transition of Native American hunting-gathering economies to more sedentary
      economies would predictably be linked to an increased incidence of treponematosis
      due to the loss of benefits of the above-stated partial immunity. In other words,
      as prehistoric Native American exposure to tick vectors for B. burgdorferi
      decreased, susceptibility to treponematosis increased. Inferences regarding
      biological controls interacting with and influencing prehistoric Native American
      migration patterns are suggested from the link of B. burgdorferi to an Ixodid
      tick common to northeast Asia.

PMID- 9637187
TI  - Variation in epinephrine and cortisol excretion rates associated with behavior in
      an Australian Aboriginal community.
AB  - Urinary epinephrine and cortisol hormone output in a remote Australian Aboriginal
      community was on average about twice as high in those individuals measured on a
      Thursday or Friday as those measured at the beginning of the next week (Monday or
      Tuesday). Diastolic blood pressure was about 6 mm Hg higher in the Thursday
      Friday group, but the difference in mean systolic blood pressure between the day
      groups does not reach statistical significance. These physiological differences
      are associated with a marked dichotomy in behavior in the two time periods: on
      the first 2 days, virtually all adults were involved in intense gambling activity
      for large stakes, but this was not a feature of the latter period. This behavior
      pattern occurs on a regular weekly basis. If substantiated by longitudinal
      studies, this phenomenon may provide an additional link between human behavior
      and a poor health profile mediated via the physiological consequences of high
      stress hormone output.

PMID- 9637188
TI  - Brief communication: gender and sex: vive la difference.
AB  - The distinction prevalent in the social sciences between the terms sex and gender
      is a useful one and ought to be preserved. Sex refers to the anatomical or
      chromosomal categories of male and female. Gender refers to socially constructed
      roles that are related to sex distinctions. Use of these terms as synonyms is
      becoming increasingly frequent in physical anthropology, especially among
      bioarchaeologists and primatologists. A failure to make the distinction between
      gender and sex is analytically incapacitating in a field such as physical
      anthropology, whose strength lies in the integration of biological and cultural
      information.

PMID- 9637189
TI  - The effects of caffeine on the maximal accumulated oxygen deficit and short-term
      running performance.
AB  - The purpose of this study was to evaluate the effect of acute caffeine ingestion
      on the maximal accumulated oxygen deficit (MAOD) and short-term running
      performance. Nine well-trained males performed a preliminary assessment and, at
      least 4 days later, a supramaximal run to exhaustion. Their VO2max values were
      determined, and the MAOD test at an exercise intensity equivalent to 125% VO2max
      was performed. Caffeine (5 mg x kg(-1)) or placebo was administered 1 hr prior to
      the MAOD in a double-blind, randomized cross-over study. In comparison to the
      placebo condition, subjects in the caffeine condition developed a significantly
      greater MAOD and increased their run time to exhaustion. However, post-MAOD blood
      lactate concentration ([HLa]) was not different between trials for caffeine and
      placebo. Caffeine ingestion can be an effective ergogenic aid for short-term,
      supramaximal running performance and can increase MAOD. However, these results do
      not appear to be related to an increased [HLa].

PMID- 9637190
TI  - Vitamin E concentration in rat skeletal muscle and liver after exercise.
AB  - The purpose of this study was to determine whether submaximal exercise
      significantly changes the concentration of vitamin E (alphaToc) in rat liver and
      skeletal muscle and to establish a time course for the return to basal levels.
      Male Sprague-Dawley rats, age 8 to 10 weeks, were randomly divided into sedentary
      control (Con) (n = 7) and exercise (n = 17) groups. Exercised animals ran 100 min
      on a motorized treadmill at approximately 70% VO2max for 3 consecutive days. They
      were then sacrificed immediately postexercise (0Post), 24 hr post (24Post), or 72
      hr post (72Post). The gastrocnemius, red vastus lateralis (RV), white vastus
      lateralis (WV), and liver were excised and analyzed for alphaToc concentration by
      high-performance liquid chromotography utilizing electrochemical detection. We
      found that after 3 consecutive days of exercise, alphaToc was reduced in RV and
      WV at 0Post and 24Post but returned to control values by 72Post. Liver alphaToc
      content was not changed at 0Post but was significantly reduced at 24Post and
      72Post. No significant changes in alphaToc were observed in the gastrocnemius in
      response to exercise. The data indicate that following an exercise-related
      decrease, skeletal muscle vitamin E concentration requires more than 24 hr to
      return to the preexercise concentration, and that the replenishment process may
      involve redistribution of vitamin E from liver to muscle.

PMID- 9637191
TI  - Body composition and nutritional assessments in soccer.
AB  - This review summarizes results from studies investigating the physical
      characteristics, daily energy expenditures, diets, and effects of nutritional
      supplements to the habitual diets of soccer players. The results show that
      players fall within a wide range of stature and body weight, and they are
      classified as mesomorphs. The body fat of male players is about 10% of body
      weight, whereas the average for females is about 21%. Energy expenditure for
      males is about 4,000 kcal on training days and 3,800 kcal on match day, while
      energy intake reported in other studies is on the order of 3,700 kcal.
      Carbohydrate (CHO), fat, and protein intakes are about 53, 30, and 14% of energy
      intake, respectively, the remaining being from alcohol intake. There are
      indications that CHO supplements might be beneficial during soccer performance.
      However, more research is needed to clarify the importance of branched-chain
      amino acid and creatine supplementation in soccer.

PMID- 9637192
TI  - Nutrition, exercise, and bone status in youth.
AB  - The maximal amount of bone mass gained during growth (peak bone mass) is an
      important determinant of bone mass in later life and thereby an important
      determinant of fracture risk. Although genetic factors appear to be primary
      determinants of peak bone mass, environmental factors such as physical activity
      and nutrition also contribute. In this article, bone growth and maintenance are
      reviewed, and mechanisms are described whereby physical activity can affect bone
      mass. Studies addressing the effects of physical activity on bone status in youth
      are reviewed: Although conclusive data are not yet available, considerable
      evidence supports the importance of activity, especially activity initiated
      before puberty. The critical role of energy in bone growth is outlined, and
      studies assessing the impact of calcium intake during childhood and adolescence
      are reviewed. Although results of intervention trials are equivocal, other
      evidence supports a role for calcium intake during growth. Recommendations for
      physical activity and nutrition, directed to children and adolescents, are
      presented.

PMID- 9637193
TI  - Resistance training and energy balance.
AB  - In this brief review we examine the effects of resistance training on energy
      expenditure. The components of daily energy expenditure are described, and
      methods of measuring daily energy expenditure are discussed. Cross-sectional and
      exercise intervention studies are examined with respect to their effects on
      resting metabolic rate, physical activity energy expenditure, postexercise oxygen
      consumption, and substrate oxidation in younger and older individuals. Evidence
      is presented to suggest that although resistance training may elevate resting
      metabolic rate, it does not substantially enhance daily energy expenditure in
      free-living individuals. Several studies indicate that intense resistance
      exercise increases postexercise oxygen consumption and shifts substrate oxidation
      toward a greater reliance on fat oxidation. Preliminary evidence suggests that
      although resistance training increases muscular strength and endurance, its
      effects on energy balance and regulation of body weight appear to be primarily
      mediated by its effects on body composition (e.g., increasing fat-free mass)
      rather than by the direct energy costs of the resistance exercise.

PMID- 9637194
TI  - Energy balance in young athletes.
AB  - Very little is known about the energy needs of young athletes. Recent studies
      using the doubly labeled water method have shown that the recommended dietary
      allowances for energy may be too high for normally active children and
      adolescents living in affluent societies. No studies of energy balance in young
      athletes have been published. Self-report dietary records of young athletes
      indicate that energy, carbohydrate, and select micronutrient intakes of certain
      athletic groups and individual athletes may be marginal or inadequate. Potential
      consequences of inadequate energy and nutrient intakes in young athletes include
      poor bone health, fatigue, limited recovery from injuries, menstrual dysfunction
      in female athletes, and poor performance. Studies of energy balance and nutrient
      status in young athletes are needed to better understand the nutritional needs of
      this group.

PMID- 9637195
TI  - Effective fluid replacement.
AB  - As a result of exercise-induced sweating, athletes and trained individuals can
      lose up to 3 L of fluid per hour. Fluid replacement is required to maintain
      hydration and allow the athlete to continue to perform. Inadequate fluid intake
      will adversely affect temperature regulation, cardiovascular function, and muscle
      metabolism. To maximize fluid intake and effectively replace fluid, athletes must
      employ behavioral strategies. Athletes can also select beverages with
      characteristics that complement their behavioral efforts. Palatability, rapid
      absorption, retention of the fluid, and ergogenicity are the major attributes to
      consider for enhancing hydration during training and physical activity.

PMID- 9637196
TI  - An advertising campaign designed to sell videotapes for an exercise regimen
      called the Campitelli Advanced 10-Minute Speed Exercise Method.

PMID- 9637197
TI  - Laminin-alpha2 (merosin), beta-dystroglycan, alpha-sarcoglycan (adhalin), and
      dystrophin expression in congenital muscular dystrophies: an immunohistochemical
      study.
AB  - Muscle biopsies of 13 congenital muscular dystrophy (CMD) patients were
      investigated for the expression of laminin-alpha2 (merosin), beta-dystroglycan,
      alpha-sarcoglycan (adhalin) and dystrophin. Expression of these proteins was
      normal in six out of eight patients with pure-CMD, in three non-Japanese patients
      clinically resembling Fukuyama-CMD (F-CMD), and in two patients with Walker
      Warburg syndrome (WWS). The two 'pure'-CMD patients with white matter hypodensity
      showed severely decreased laminin-alpha2 expression and normal expression of the
      other proteins. Our findings in the non-Japanese patients, clinically resembling
      F-CMD, are different from those in Japanese cases with F-CMD in the literature.
      Consequently, our patients suffer from WWS or from another yet undetermined form
      of CMD.

PMID- 9637198
TI  - Postoperative intracranial abscess--clinical aspects in the differential
      diagnosis to early recurrence of malignant glioma.
AB  - Out of 2941 patients who received a clean, major craniotomy, 39 patients (1.3%)
      developed the complication of an intracranial deep infection, i.e. abscess or
      empyema. A total of 14 patients with a postoperative abscess were initially
      operated upon intracerebral malignant glioma (WHO III or IV) and could be
      compared to a matched group of patients with recurrent malignancy concerning
      clinical and radiological aspects. A statistically significant elevation of
      median values was seen for erythrocyte sedimentation rate (ESR), fibrinogen and
      body temperature in the study group. C-reactive protein (CRP) was not
      investigated in the control group and could not be compared, but it was elevated
      in all abscess patients when measured. CT-scan did not allow a safe
      differentiation between infection and recurrent glioma. Local signs like
      suppuration of the wound could be observed in 71% of patients with intracranial
      infection. Postoperative abscesses had been diagnosed in all cases within 3
      months, whereas none of the early recurrences of intracerebral malignoma became
      symptomatic before 12 weeks after initial operation. Therefore, the course of
      time seems to be another important factor in this differential diagnosis.

PMID- 9637199
TI  - Genetic and environmental risk factors in Parkinson's disease.
AB  - Parkinson's disease (PD) is a multifactorial disorder, caused by a combination of
      age, genetics and environmental factors. Nigral cells are susceptible to multiple
      causes of derangement of normal cell function, all of which may contribute to the
      same Parkinson phenotype. Autosomal dominant alpha-synuclein-gene PD represents
      one of the pure genetic forms, whereas cases of sporadic PD probably depend more
      on age and environmental factors, MPTP-Parkinsonism being the purest example of
      an environmentally caused Parkinson phenotype. This review suggests that
      pesticides-herbicides, smoking and head trauma probably represent the most
      eligible candidates for environmental factors involved in provoking PD or
      influencing its natural course.

PMID- 9637200
TI  - Proton magnetic resonance spectroscopy in deep cerebral venous thrombosis.
AB  - A 63-year-old man developed a severe left frontal headache followed by an acute
      change of mentality 6 days later. Magnetic resonance imaging revealed bilateral
      thalamic ischemia. Angiography confirmed the occlusion of deep cerebral veins.
      Proton magnetic resonance spectroscopy (1H-MRS) of the thalami showed normal N
      acetylaspartate (NAA) peak and the presence of lactate peak, indicating a
      relatively preserved neuronal viability. The patient improved during the follow
      up period, and returned to work 45 days after the onset of the disease. With 1H
      MRS, prognosis following venous infarctions may be feasible.

PMID- 9637201
TI  - Transient visual blurring, retro-orbital pain and repetitive involuntary
      movements in unilateral carotid artery occlusion.
AB  - An 83-year-old man presented with episodes of right sided retro-orbital pain,
      visual disturbance, involuntary jerks of his left arm and less frequently his
      left leg. The symptoms could be triggered by exercise, heat or cough. EEG
      recordings revealed no epileptic discharges. Duplex ultrasonography showed an
      occlusion of the right internal carotid artery. Blood flow velocity in the right
      middle cerebral artery was reduced and vasomotor reactivity to hypercapnia was
      absent. Reduction of his antihypertensive medication rendered the patient
      asymptomatic. The combination of transient visual blurring, retro-orbital pain
      and contralateral limb shaking can be an unusual manifestation of carotid
      occlusive disease. In such a case, the symptoms may be managed successfully by
      the elevation of blood pressure.

PMID- 9637202
TI  - Intracranial hypotension syndrome: neuroimaging in five spontaneous cases and
      etiopathogenetic correlations.
AB  - Intracranial hypotension (IH) is essential or, more frequently, secondary. This
      syndrome is characterized by severe postural headache and low opening
      cerebrospinal fluid (CSF) pressure; although other symptoms may exist. In this
      study five patients are investigated. Neuroimaging showed: on computerized
      tomography scan (CT), poor visualization of the cerebral sulci with small
      ventricles; on magnetic resonance imaging (MRI), subdural fluid collections with
      enhancement on the convexity, along the tentorium and in the upper cervix after
      administration of contrast medium and downward displacement of the brain.
      Radionuclide cisternography was normal in the two patients who underwent this
      treatment as well as the meningeal biopsy in another patient. In all patients the
      opening CSF pressure was low or unmeasurable. The clinical syndrome spontaneously
      recovered contextually to normalization of neuroradiological findings. The
      possible pathogenesis (dural border cell layer tear) was discussed and the
      importance of diagnostic confirmation with MRI and measurement of CSF pressure
      when IH is thought to be present was underlined.

PMID- 9637203
TI  - Visual improvement during octreotide therapy in a case of episellar meningioma.
AB  - Meningiomas of the tuberculum sellae can induce compression of the optic tract.
      We report the case of a 54-year-old female patient affected by a suspected
      pituitary macroadenoma with severe visual field defects, who experienced a
      significant clinical and visual improvement during short-term octreotide therapy,
      contrasting with the lack of neuroradiological evidence for tumor shrinkage. The
      patient subsequently underwent transcranial surgery with a final diagnosis of
      meningioma. The putative mechanisms of visual improvement during octreotide
      therapy are discussed.

PMID- 9637204
TI  - The forgotten condyle: Delayed hypoglossal nerve palsy caused by fracture of the
      occipital condyle.
AB  - Fracture of the occipital condyle is a rare injury that can be easily overlooked.
      Palsies of lower cranial nerves can be the only symptom of the fracture. We
      report a patient with isolated post-traumatic hypoglossal nerve palsy who
      developed hypoglossal nerve palsy within 2 months after a car accident,
      indicating that the acute trauma itself did not damage the hypoglossal nerve.
      Most likely the palsy is caused by pressure to the nerve prior to the entry or
      within the hypoglossal canal. Since, in the present case, the fracture was stable
      and the patient showed only moderate neurological deficits, the operation was
      deferred.

PMID- 9637205
TI  - Posthemiplegic focal limb dystonia: a report of two cases.
AB  - Posthemiplegic focal limb or hemidystonias are rare movement disorders usually
      due to vascular lesions of the contralateral basal ganglia. The pathogenesis of
      posthemiplegic dystonia is unknown and its management is usually difficult. In
      this paper, we report two patients who suffered from a single limb dystonia and
      hemidystonia, respectively. In the latter patient, hemidystonia developed due to
      an ischaemic cerebrovascular accident 2 or 3 months after the recovery of
      hemiplegia. Computed tomography and magnetic resonance imaging scans showed
      evidence of contralateral putamen and thalamus infarcts.

PMID- 9637206
TI  - Reversible blindness in AIDS-related cryptococcal meningitis.
AB  - A 30-year-old AIDS-patient with cryptococcal meningitis developed subacute
      bilateral visual loss associated with high cerebrospinal fluid (CSF) pressure.
      With immediate CSF drainage the blindness was reversible. The importance of
      prompt CSF drainage in AIDS-related cryptococcal meningitis with visual failure
      is stressed.

PMID- 9637207
TI  - Demyelinating polyneuropathy with preferentially-proximal involvement.
AB  - A 47-year-old man showed progressive, symmetrical weakness in the limbs for 6
      months. There was muscle atrophy, fasciculations, and acute denervation without
      motor conduction abnormalities below the elbows or knees, and motor neuron
      disease had once been suspected. However, compound muscle action potentials
      (CMAPs) after proximal stimulation showed an amplitude reduction between axilla
      and Erb's point for the median and ulnar nerves on both sides. His weakness as
      well as the amplitude reduction improved after administration of prednisolone.
      Demyelinative conduction abnormalities can be limited to the proximal segments
      for at least several months in a conduction equivalent to chronic inflammatory
      demyelinating polyneuropathy (CIDP).

PMID- 9637208
TI  - Malignant cerebellar astrocytoma developing 15 years after radiation therapy for
      a medulloblastoma.
AB  - A case of malignant cerebellar astrocytoma occurring 15 years after the radiation
      therapy for a medulloblastoma is reported. The tumor developed at the same site
      of irradiation after a sufficient latent period and was completely different from
      medulloblastoma in its histology. This tumor fulfilled the criteria of radiation
      induced neoplasm. Only seven similar cases have been reported up to the present.
      Whole neuraxis irradiation following a gross total resection is a standard
      treatment for medulloblastoma, but the possibility of the development of
      radiation-induced tumors must be borne in mind for a long time after the
      radiation therapy for medulloblastoma.

PMID- 9637209
TI  - Beneficial gamma-knife radiosurgery in a patient with Nelson's syndrome.
AB  - A 50-year-old female patient with Cushing's disease had undergone transsphenoidal
      removal of the pituitary adenoma and conventional radiotherapy in 1988. Since no
      remission was achieved, she underwent bilateral adrenalectomy in May 1989. During
      out-patient follow-up, she developed signs and symptoms due to invasive
      Adrenocorticotrophic hormone (ACTH)-producing macroadenoma (Nelson's syndrome) in
      1994. ACTH levels at that time were 3400 ng/l. Near-total surgical resection of a
      2.0 x 2.5 pituitary tumour which slightly extended laterally into the cavernous
      sinus was achieved by subfrontal approach in June 1994. However, she rapidly
      developed a recurrence of her complaints, with a visual field defect inferior
      nasal of the left eye, and a second operation was carried out in November 1994.
      Culture of the tumour's cells revealed significant inhibition of ACTH production
      by bromocriptine. Adjuvant treatment with this drug therefore was started in
      November 1994. Because of the rapid recurrence it was decided to treat her with
      gamma-knife radiosurgery. The dose that was given in January 1995 was 12 Gy to
      the border and 40 Gy into the centre of the tumour. During a follow-up of more
      than 2 years, no recurrence, but even a minor reduction of tumour mass was
      observed by magnetic resonance imaging (MRI). Plasma ACTH levels decreased
      gradually to levels between 200 and 400 ng/l, and ophthalmologic complaints
      disappeared. It is concluded that gamma-knife radiosurgery may be a good
      alternative for patients with Nelson's syndrome who have rapidly recurring
      disease.

PMID- 9637210
TI  - A new form of complicated hereditary spastic paraplegia with cataracts, atretic
      ear canals and hypopigmentation.
AB  - A 16-year-old Hispanic boy born of consanguineous parents is described as having
      a history of cataracts, progressive lower-extremity spasticity and atrophy
      starting at 4 years of age, atretic ear canals with hearing dysfunction and
      diffuse patchy cutaneous hypopigmented areas. Clinical examination showed the
      typical signs of spastic paraplegia with increased tone, hyperreflexia, muscle
      atrophy and contractures. Sensation, autonomic and cerebellar functions were not
      disturbed. Neuroimaging studies were normal. Laboratory findings did not support
      a diagnosis of metabolic disturbance or infectious disease. This is considered a
      new form of complicated hereditary spastic paraplegia (HSP), transmitted
      presumably in an autosomal recessive pattern.

PMID- 9637211
TI  - Vestibular schwannoma with repeated intratumoral hemorrhage.
AB  - A symptomatic hemorrhage from a vestibular schwannoma is extremely rare, despite
      its relatively high incidence in the cerebellopontine angle. Much more unusual
      are repeated intratumoral hemorrhages. The authors report on such a rare case of
      repeated intratumoral hemorrhage from a vestibular schwannoma, presenting with
      sudden exacerbation of headache, nausea and vomiting. This second hemorrhage was
      confirmed by CT scan on the day of the onset of symptomatic exacerbation, which
      was 9 days after the initial CT scan, showing an enlarged amount of blood within
      the tumor. The MRI scan confirmed this CT finding. After removal, the tumor
      proved to be a typical vestibular schwannoma of mixed Antoni types A and B. Thin
      dilated vessels with hemorrhage and hemosiderin-laden macrophages were observed.
      The patient's postoperative course was uneventful. A total of 28 reported cases
      of a single intratumoral hemorrhage in vestibular schwannomas, and one reported
      case of repeated hemorrhage are reviewed.

PMID- 9637212
TI  - Familial cortical tremor with epilepsy: an under-recognized familial tremor.
AB  - The authors report three Japanese families presenting with cortical tremor and
      epilepsy. The patients showed either tremulous finger movements or seizures as
      the initial symptoms between 19 and 30 years of the age without progression.
      Postural tremor resembled essential tremor and responded to the anticonvulsants
      such as clonazepam, primidone and sodium valproate. Seizures were infrequent.
      These patients seem to have the same disorder as what the authors have described
      as 'familial cortical tremor with epilepsy'. Familial cortical tremor must be
      more common than previously thought and should be taken into consideration in the
      patients with 'familial essential tremor' who do not respond well to beta
      blockers.

PMID- 9637213
TI  - Seroprevalence of Babesia ovis in Spanish ibex (Capra pyrenaica) in Catalonia,
      northeastern Spain.
AB  - A serologic survey was carried out in order to detect antibodies against Babesia
      ovis in a large population of Spanish ibex (Capra pyrenaica) from a hunting
      reserve in Catalonia, northeastern Spain. For this purpose, an indirect
      fluorescent antibody test (IFAT) was developed using a B. ovis isolate of ovine
      origin as antigen. Of the total 475 sera tested, 155 (32.6%) showed titres
      between 1:160 and 1:1280 and were considered positive. These results reveal that
      exposure of Spanish ibex to B. ovis is common in the studied area. No significant
      differences could be detected when comparing season or year of capture and age or
      sex of the animals in positive and negative samples. A high proportion of low
      titres was found in comparison to those reported by other researchers in sheep in
      Spain; this could be a consequence of the existence of some minor antigenic
      differences between B. ovis of domestic sheep and that found in Spanish ibex.

PMID- 9637214
TI  - The efficacy of Michel's dose and move system on gastrointestinal nematode
      infections in diary calves.
AB  - The efficacy of a move to aftermath in July combined with moxidectin or
      fenbendazole treatment for the control of parasitic gastroenteritis (PGE) in
      calves was evaluated in three field experiments in the Netherlands. In all five
      treated groups high gastrointestinal nematode infections and PGE were prevented
      by a dose and move in July. Cooperia infections increased to moderate levels in
      two groups treated with moxidectin and one group treated with fenbendazole. In
      both other groups and also for Ostertagia in these three groups, low to extremely
      low infections were acquired. In the first experiment high primary infections,
      resulting in high faecal egg counts and a moderate increase of blood pepsinogen
      values occurred before the dose and move. Nevertheless, these primary infections
      were not high enough to result in PGE. In both other experiments primary
      infection levels were low and faecal egg counts increased to 100-650 eggs/g
      faeces at the end of the grazing season. The blood pepsinogen values of non
      treated control groups demonstrated that it took more than a month after their
      move to aftermath before substantial reinfection occurred on the new pasture. In
      the first and the last experiment only, high Ostertagia and Cooperia infections
      developed in the control group at the end of the grazing season, though it did
      not result in clinical PGE. The experiments demonstrate all theoretical risks of
      the dose and move system: (1) PGE early in the grazing season as a result of high
      overwintered pasture infectivity. (2) PGE just before the move as a result of an
      early midsummer increase in pasture infectivity. (3) PGE around housing as a
      result of insufficient suppression of pasture infectivity late in the grazing
      season. (4) Underexposure to nematode infections due to a high suppression of
      nematode infections. Nevertheless, it can be concluded that under normal
      conditions the dose and move system remains to be a valuable and easily
      applicable system for the control of PGE.

PMID- 9637215
TI  - Gastrointestinal nematode infections of first-grazing season calves in Western
      Europe: general patterns and the effect of chemoprophylaxis.
AB  - Research on the prevention of gastrointestinal nematode infections of cattle has
      mainly concentrated on comparing a specific chemoprophylactic treatment system to
      an untreated control group on a particular farm. Here, the results from analysis
      of 85 studies involving over 2000 first grazing season (FGS) calves put onto
      pasture for at least 4 months from late spring/early summer over a 26-year period
      in 13 countries in Western Europe are presented. Both control and
      chemoprophylactic treated FGS calf groups were considered. All chemoprophylactic
      systems (slow- and pulse-release boli, strategic treatments) were given early in
      the grazing season. Two general infection levels emerged--'sub-clinical' (32
      studies) and 'clinical' (53 studies). The 'sub-clinical' infections were
      characterised by no clinical symptoms of parasitic gastroenteritis (PGE) being
      observed in the control groups. Mean faecal egg counts in the 'clinical' control
      groups were significantly higher than those for 'sub-clinical' control groups for
      almost the entire season with overall peaks of 275 and 100 EPG respectively.
      Maximum pasture larval counts were also significantly higher in the 'clinical'
      control groups with 44% of 'clinical' pastures > 10,000 L3 kg(-1) dry herbage by
      the end of the FGS, compared to only 15% of 'sub-clinical' pastures. There was a
      significant positive relationship between log transformed worm burdens from
      tracers put onto pastures for 2 weeks and the corresponding pasture larval count.
      No evidence of density dependence in tracer worm burden was observed. Weight
      gains in the 'clinical' control groups (375 g/day) were significantly lower than
      those of the 'sub-clinical' control groups (530 g/day). No symptoms of PGE were
      observed in any of the chemoprophylactic treated groups, but in those studies
      with an outbreak of PGE in the control group, the treated groups had
      significantly higher faecal egg and pasture larval counts than treated groups in
      'sub-clinical' studies. The overall weight gain in chemoprophylactic treated
      calves in 'clinical' studies (600 g/day) was significantly lower than the
      chemoprophylactic treated calves in 'sub-clinical' studies (690 g/day), and was
      not significantly different from the weight gain of control calves in 'sub
      clinical' studies. These results indicate that on heavily infected pastures,
      chemoprophylaxis will prevent PGE, but calves will still suffer production
      losses.

PMID- 9637216
TI  - Gastrointestinal nematode infections of first-grazing season calves in Western
      Europe: associations between parasitological, physiological and physical factors.
AB  - Analysis of 85 studies on gastrointestinal nematode infections in first-grazing
      season (FGS) calves is presented. The studies cover a 26-year period and were
      carried out in 13 countries in Western Europe. Both control and chemoprophylactic
      treated (early in the season) FGS calf groups were included. In 53 of the 85
      studies, clinical outbreaks of parasitic gastroenteritis (PGE) were observed
      during the FGS in the control groups. The mean initial age (and weight) of the
      control calf group was significantly associated with PGE outbreaks: 82% of
      control calf groups < or = 6 months of age had outbreaks of PGE, compared to only
      33% of control calf groups > 6 months of age. In 92% of trials where the
      geometric mean faecal egg count (MFEC) was > or = 200 EPG on Day 56, PGE
      outbreaks were observed, but where it was < 200 EPG, only 29% had PGE. The use of
      these two factors in assessing the likelihood of PGE outbreaks in untreated calf
      groups in the future FGS is therefore, proposed. No chemoprophylactic-treated
      groups had PGE, but there was a highly significant negative relationship between
      maximum faecal egg counts in the chemoprophylactic-treated calves and the
      proportion of the trial covered by the different chemoprophylactic systems.
      Higher stocking densities were significantly associated with higher pasture
      contamination in both control and chemoprophylactic-treated calves. A highly
      significant positive relationship between the weight gained in the
      chemoprophylactic-treated groups and the estimated duration of the various
      chemoprophylactic systems was found, but there were large variations in weight
      gains (60-160 kg) between groups even with the same chemoprophylactic. Despite
      this and other highly significant associations, it was not possible to indicate
      what weight gains were obtained by the end of the FGS, from factors measured
      early in the FGS.

PMID- 9637217
TI  - The effect of different infection levels on acquired resistance to
      gastrointestinal nematodes in artificially infected cattle.
AB  - The objective of this study was to evaluate the effect of different infection
      levels of Ostertagia ostertagi and Cooperia oncophora in a simulated 'first
      grazing season' on the resistance of calves to an artificial challenge infection.
      The infection levels were determined by the infection schedules and the
      chemoprophylaxis used. Thirty six 7-11-month old Holstein-Friesian bull calves
      were randomly divided into four groups. The animals of group B received an
      ivermectin sustained release bolus (ISRB) on day 0. The calves of group D were
      treated on days 0 and 56 with a subcutaneous injection of doramectin (0.2 mg kg(
      1) BW). Group C was the untreated control group. The calves of group N were used
      as helminth-naive controls, while the animals of groups B, C and D were trickle
      infected for 24 weeks. The infection schedules were designed to simulate the
      expected infection pattern for each treatment group under set-stocked conditions
      in temperate climate areas. After the last infection, all animals were treated
      with oxfendazole. One week later, all animals received a challenge infection of
      50,000 O. ostertagi L3 and 100,000 C. oncophora L3, spread over 10 consecutive
      days. During the primary infection period the faecal egg output and the serum
      pepsinogen and antibody levels reflected the different levels of host-parasite
      contact between the groups (group C > group D > group B > group N). After the
      challenge infection, faecal egg counts, total Ostertagia burden, size of the
      adult worms and abomasal globule leucocyte counts all indicated a positive
      relationship between the level of Ostertagia infection during the primary
      infection period and the level of acquired resistance. A reduction of host
      parasite contact during the primary infection period, as a consequence of the
      infection schedule and the chemoprophylaxis used, resulted in a diminished level
      of resistance to the artificial challenge infection with O. ostertagi. Faecal
      cultures and small intestine worm counts indicated that all previously infected
      groups had acquired a high degree of resistance to the Cooperia challenge
      infection.

PMID- 9637218
TI  - Field evaluation of a topical doramectin formulation for the chemoprophylaxis of
      parasitic bronchitis in calves.
AB  - A study was conducted to evaluate the efficacy of two topical treatments with
      doramectin on the season-long control of lungworm and gastrointestinal infections
      in first grazing season (FGS) calves. At the start of the study, 20 FGS calves
      were randomly allocated into two treatment groups of 10 animals each. Calves in
      the D-group were treated with doramectin pour-on on days 0 and 56, at a dosage of
      500 microg kg(-1) BW: calves in the C-group were designated as controls. A
      permanent pasture was divided in two blocks and these were randomly allocated to
      the treatment groups. Throughout the study, tracers (n = 32) were grazed on each
      paddock at 3-week intervals. Clinical signs of parasitic bronchitis (PB) were
      observed in the C-group in July and this necessitated two salvage treatments with
      levamisole. From day 28, post-turnout lungworm larvae were recovered from faeces
      of the C-calves until housing. No signs of PB were observed in the D-group during
      the entire grazing season. Shedding of lungworm larvae in the principals of the D
      group did not occur until 112 days post-turnout. From the data obtained from the
      tracer calves. it appeared that larvae had overwintered on both pastures. On the
      C-pasture, the number of lungworms recovered from the tracer calves gradually
      increased to a peak in September, whereas on the D-pasture, the increase was
      observed only at the end of the pasture season. Both strongyle faecal egg counts
      and pepsinogen levels were relatively low in both groups throughout the present
      study. At the end of the grazing period (day 161). the principals were housed and
      treated with oxfendazole. During the housing period, all principal animals (D-
      and C-groups) and a third group of four helminth free animals (N-group) received
      a challenge infection with Dictyocaulus viviparus. It appeared that the different
      exposure to the parasite during the grazing season resulted in different
      establishment rates, i.e.. group C < group D < group N. The present results show
      that overwintering of lungworm larvae occurs in Belgium and that in such
      conditions, doramectin pour-on given at turnout and at 8 weeks controls PB in
      calves during the first grazing season.

PMID- 9637219
TI  - Embryonation and infectivity of Ascaris suum eggs isolated from worms expelled by
      pigs treated with albendazole , pyrantel pamoate, ivermectin or piperazine
      dihydrochloride.
AB  - The effect of anthelmintic treatment of pigs on the embryonation and infectivity
      of Ascaris suum eggs isolated from expelled worms was investigated. Four groups
      of two naturally infected pigs were dosed with albendazole, pyrantel pamoate,
      ivermectin or piperazine dihydrochloride, respectively. Following worm expulsion,
      the eggs were removed from the uteri of female worms and embryonated in sulphuric
      acid. The infectivity of the embryonated eggs was tested through mouse
      inoculation. Egg development appeared normal in cultures from worms of the
      piperazine. pyrantel and ivermectin treated groups. In the albendazole cultures,
      egg development was largely arrested at the one-cell stage (81%). Where
      development occurred, irregular cell division was observed and only 7% of the
      eggs in the culture developed into fullgrown larvae. Following mouse inoculation
      with 2500 embryonated eggs, significantly lower lung larval counts on day 8 post
      inoculation (p.i.) were observed for mice in the piperazine and pyrantel treated
      groups (P < 0.01) compared to untreated controls. The larvae that developed in
      the eggs from ivermectin and albendazole treated groups appeared fully infective
      for mice. It was concluded that ovicidal activity of albendazole in vivo inhibits
      subsequent A. suum egg development in vitro; albendazole is, therefore, not
      suitable to obtain worms for egg embryonation to produce experimental inoculums.
      The anthelmintic treatment of pigs with ivermectin had only a limited effect on
      both embryonation and infectivity of A. suum eggs isolated from expelled worms.

PMID- 9637220
TI  - Multiple anthelmintic resistance on a goat farm in Kenya.
AB  - The anthelmintic efficacy of benzimidazoles, levamisole, rafoxanide and
      ivermectin was evaluated on an institutional farm in Kenya using faecal egg count
      reduction test, larval cultures and a controlled slaughter trial. The results of
      this study indicated simultaneous resistance of Haemonchus contortus against
      benzimidazoles, levamisole and rafoxanide and Trichostrongylus columbriformis and
      Oesophagostomum sp. against levamisole on the same farm. Injectable and orally
      administered ivermectin was effective against the benzimidazole and levamisole
      resistant H. contortus.

PMID- 9637221
TI  - Interpreting comparative experiments on parasite burdens in animals using
      randomization and canonical variates.
AB  - Comparative experiments on parasite burdens present difficulties for modelling
      and interpretation: data tend to have highly skewed distributions, some standard
      methods of testing for effects have low power, and there is a need to make
      allowance for dependencies among the various measurements. Randomization testing
      and canonical variates analysis are advocated as a means of minimising these
      problems.

PMID- 9637222
TI  - Methimazole-mediated enhancement of albendazole oral bioavailability and
      anthelmintic effects against parenteral stages of Trichinella spiralis in mice:
      the influence of the dose-regime.
AB  - The influence of methimazole (MTZ) inhibitor of the microsomal oxidases on the
      systemic availability of the albendazole sulpho-metabolites (ABZS-MT) albendazole
      sulphoxide (ABZSO) and albendazole-sulphone (ABZSO2) and on its anthelmintic
      effects was investigated in a mouse model for helminthic infections. Plasma
      concentrations of the ABZS-MT were measured by high performance liquid
      chromatography (HPLC) following treatment of Swiss CD-1 mice with albendazole
      (ABZ) alone or ABZ plus MTZ, at both single and repeated doses. The anthelmintic
      effects were assessed in age-matched mice similarly treated following infection
      with Trichinella spiralis. MTZ significantly (p < 0.01) increased the ABZS-MT
      plasma concentrations although the pharmacokinetic profile varied greatly
      according to the dose of ABZ administered. When ABZ was given at a single dose of
      50 mg/kg followed by MTZ at 3 mg/kg, a cumulative effect was observed in the ABZS
      MT plasma levels with pharmacokinetic parameters (Tmax = 24 h, Cmax= 30.88
      microg/ml and AUC = 1120.80 microg h/ml) significantly ( p < 0.01) higher than
      those following administration of ABZ alone (Tmax = 3 h, Cmax = 11.00 microg/ml
      and AUC = 268.03 microg h/ml). This cumulative effect was absent following
      administration of ABZ at 100 mg/kg where, after reaching a maximum (Cmax = 27.23
      microg/ml) at 3 h post-administration (Tmax), the ABZS-MTplasma levels felt down
      quickly to values under those obtained after administration of ABZ at the same
      dose, but alone (AUC = 362.15 microg h/ml vs. 340.15 microg h/ml, respectively).
      When ABZ was given at 50 mg/kg together with MTZ three times every 24 h, a rapid
      decrease was observed in the ABZS-MT plasma levels following administration of
      both the second and third doses, respectively. The pharmacokinetic profile of
      ABZS-MT following administration of each of the three doses of ABZ at 100 mg/kg
      plus MTZ was the same as that obtained after the single treatment. The rapid
      decrease of the ABZS-MT plasma levels observed after the sustained treatment or
      after the single treatment at 100 mg/kg could be due to a microsomal oxidase
      inductive effect (probably the cytochrome P-450) caused by ABZSO. The co
      administration of MTZ significantly (p < 0.01) increased the anthelmintic effects
      of ABZ against both migrating and encysted larvae of T. spiralis. Repeated
      treatment did not improve the anthelmintic effects of the single treatment as the
      efficacies against both stages of the parasite were always lower or identical to
      those of the single treatment at the corresponding doses.

PMID- 9637223
TI  - The prevalence of Dirofilaria immitis in Gran Canaria, Canary Islands, Spain
      (1994-1996).
AB  - Blood samples from 2034 dogs were tested to detect Dirofilaria immitis antigen
      during three consecutive years (from 1994 to 1996) in Gran Canaria Island, Canary
      Islands, Spain. The prevalence of heartworm infection was 67.02% in 1994, 58.92%
      in 1995 and 52.18% in 1996, with a mean prevalence of 58.89%. Heartworm infection
      was more common in males (56.19%) than in females (43.81 %), in dogs aged between
      3 and 6 years old. The distribution of the disease in the different climatic
      zones was studied. Chronological changes in the dog's prevalence for heartworm
      infection in the three consecutive years and the role of the epidemiological
      factors in the changes of the positive rates were evaluated.

PMID- 9637224
TI  - Studies on the survival of Ascaris suum eggs under laboratory and simulated field
      conditions.
AB  - A series of four experiments was carried out to study the survival of Ascaris
      suum eggs: in a pig slurry unit on a farm, in the laboratory under anaerobic
      conditions and different relative humidities (rH), and under simulated field
      conditions. Survival of eggs in the pig slurry unit was 20% after four weeks and
      0% after 16 weeks. Anaerobic conditions had only a minor influence on survival:
      after 12 weeks, more than 80% of the eggs could still develop. At high relative
      humidities (100% and 75%), survival was respectively 96% and 62% after 12 weeks.
      At 47.5% rH, survival dropped to 0% after 10 weeks and at 7.5% rH in 8 weeks. A.
      suum eggs kept in pig slurry under dry and sunny outdoor conditions survived for
      2-4 weeks, whereas under wet and shady conditions, 90% of the eggs were still
      viable after 8 weeks.

PMID- 9637225
TI  - Gastrointestinal helminth parasites in stray cats from the mid-Ebro Valley,
      Spain.
AB  - Gastrointestinal helminths were collected from 58 necropsied stray cats (Felis
      catus) in the mid-Ebro Valley, North-East Spain, from December 1989 to March
      1992. The prevalence was 89.7%, with those of individual parasites being Toxocara
      cati 55.2%C, Ancylostoma tubaeforme 29.3% Joyeuxiella pasqualei 55.2%,
      Diplopylidium acanthotetra 20.7%, Dipylidium caninum 20.7%, Mesocestoides spp.
      13.8%, Taenia taeniformis 8.6% and Diplopylidium nolleri 8.6%. In relation to
      sex, the differences were not significant. However, the season of the year
      significantly affected the prevalence of A. tubaeforme and D. acanthotetra.

PMID- 9637226
TI  - Development, reproductive capacity and survival of Amblyomma variegatum and
      Boophilus decoloratus in relation to host resistance and climatic factors under
      field conditions.
AB  - To determine the developmental periods, fecundity and survival of Amblyomma
      variegatum and Boophilus decoloratus and the effect of host resistance, a study
      was carried out in the field at Abernossa ranch in Ethiopia using three breeds of
      cattle: Arssi, Boran and Boran x Friesian crossbreed. The investigation took
      place between October 1991 and September 1992. The developmental periods of both
      tick species were recorded. The hatching periods of larvae, engorgement, larvo
      nymphal and nympho-adult moulting periods during various climatic seasons in
      shaded and dry areas were also recorded. While the engorgement periods recorded
      on the animal were relatively constant for each tick species throughout the
      period of investigation, the pre-hatching and moulting periods were influenced by
      seasons. Generally, the duration of the life cycle was longest during the peak of
      rains and shortest during the dry season. In A. variegatum, the duration of the
      life cycle, irrespective of seasons, was shorter in the open than in the shaded
      site but this difference was not observed in B. decoloratus. Adults survived
      longer than nymphs, and nymphs longer than larvae in both tick species and A.
      variegatum survived much longer than B. decoloratus. All these variations were
      statistically significant (P < 0.001). A. variegatum and B. decoloratus fed on
      Boran X Friesian crossbreed cattle survived longer than ticks fed on the
      indigenous Boran and Arssi breeds, although the survival of both tick species fed
      on the latter two breeds was not significantly different from each other. The
      least tick resistant cattle (Boran X Friesian) produced the largest ticks with
      highest survival periods, whereas the most resistant indigenous cattle (Arssi and
      Boran) cattle produced the smallest ticks with the lowest survival periods. In
      all cases, more eggs were laid by A. variegatum than by B. decoloratus. However,
      in both tick species, the number of eggs laid and their hatchability were higher
      in those ticks fed on crossbreed than on indigenous cattle. The engorgement
      weights were positively correlated with the number of eggs laid and their
      hatchability.

PMID- 9637227
TI  - Efficacy of orally administered invermectin against larval stages of Oestrus ovis
      in sheep.
AB  - The efficacy of ivermectin administered orally at a dosage rate of 0.2 mg/kg
      liveweight against naturally acquired larval infestations of Oestrus ovis in
      sheep was 100% in a field trial. Ten sheep were free from infestation by first,
      second and third instar larvae of O. ovis 12 days post treatment, whereas 10
      control sheep harboured 37.7 larvae on average, most of them first stage.

PMID- 9637228
TI  - Delayed type hypersensitivity theilerin test in cattle vaccinated against
      Theileria annulata infection.
AB  - Theilerin was prepared and its total nitrogen was determined at level of 1 mg/ml.
      Seventy-two Holstein Friesian cattle recovered from acute theileriosis or
      vaccinated received 0.1 ml of theilerin intradermally at normal concentration of
      total nitrogen or other dilutions (1 / 10 and 1 / 100). Some 60(% of calves and
      66.67% of milking cows receiving normal theilerin showed more than 1 mm increase
      in skin thickness at the site of inoculation (mean value of 1.86 mm for calves
      and 3.46 mm for milking cows). The pathological examination of the inoculation
      site showed infiltration of lymphocytes. No changes of general condition were
      observed in animals under study. The result indicated that the test is positive
      and could be used for checking Immunity in vaccinated animals.

PMID- 9637229
TI  - Prevalence of Tritrichomonas foetus infection in beef bulls in northwestern
      Spain.
AB  - The purpose of this study was to investigate the prevalence of Tritrichomonas
      foetus infection in beef bulls in north-western Spain. The study area comprised
      of 350 herds (5909 cows and 102 bulls) managed under extensive or semi-extensive
      systems where natural mating alone or alternated with artificial insemination are
      used. The targets of this survey were bulls of 1 year of age or older. Preputial
      smegma samples were taken from 70 bulls (68.6% of bull population) servicing a
      total of 184 herds (52.6%) and 4136 cows (69.9%). Data collected at sampling
      included farm location, herd size, age, breed, private or communal bull and
      previous infertility problems in the herd. The percentage of infected bulls was
      2.9% (2 of 70). Age of infected bulls was 5 and 7 years and both were of the
      local breed, Asturiana de los Valles. These results confirm the presence of T.
      foetus infection in Spain and the necessity to include this disease in the
      differential diagnosis of reproductive failure in rangeland grazing cattle.

PMID- 9637230
TI  - Prevalence of Neospora caninum and Toxoplasma gondii antibodies in sera from
      camels from Egypt.
AB  - Sera from camels from Egypt were examined by the direct agglutination tests
      incorporating mercaptoethanol for antibodies to Neospora caninum and Toxoplasma
      gondii. Antibodies to N. caninum were found in 6 of 161 camels in titers of 1:40
      (2 camels) and 1:80, 1:160, 1:640, and 1:1280 in 1 camel each, using N. caninum
      formalin preserved whole tachyzoites as antigen. Antibodies to T. gondii were
      found in 17.4% of 166 camels in titers of 1:25 (3 camels), 1:50 (18 camels). and
      > 1:500 (8 camels) using T. gondii tachyzoites. All 6 camels with N. caninum
      antibodies had no T. gondii antibodies in 1:4 dilution of serum, indicating
      specificity of the reaction. This is the first report of N. caninum prevalence in
      Egypt.

PMID- 9637231
TI  - Disseminated feline leishmaniosis due to Leishmania infantum in Southern France.
AB  - A fortuitously discovered case of feline leishmaniosis is reported. The parasites
      were found in the skin and the bone marrow of a domestic female cat that
      spontaneously died after a few weeks of evolution. Serological tests for FeLV,
      FIV and PIF virus detection gave negative results. By using Western blot
      serology, a characteristic pattern of leishmaniosis was obtained and by
      performing an isoenzyme electrophoresis, a Leishmania infantum MON-1 strain was
      identified. The same zymodeme is implicated in most of the canine and human
      leishmaniosis in Southern Europe. A study on the prevalence of asymptomatic
      feline leismaniosis is foreseen.

PMID- 9637232
TI  - Preliminary studies on humoral immune response of sheep to wohlfahrtiosis.
AB  - The humoral immune response of sheep to wohlfahrtiosis was studied. An enzyme
      linked immunosorbent assay was developed to compare four different types of
      antigens obtained from the third-stage larvae of Wohlfahrtia magnifica. The
      antigen prepared from salivary glands detected a humoral response in all 35
      infested sheep and was more specific in the ELISA than cuticular, intestinal or
      whole larval antigens. The level of the humoral response in sheep to
      wohlfahrtiosis differed according to the location of the wounds.

PMID- 9637233
TI  - The genetic effects of environmental lead.
AB  - This article reviews the effects of lead on genetic systems in the context of
      lead's various other toxic effects and its abundance and distribution in the
      environment. Lead is perhaps the longest used and best recognized toxic
      environmental chemical, yet it continued be used recklessly until only very
      recently. Lead is thus a lesson in the limitations and strengths of science,
      human conscience and common sense. Lead has been tested and found to be capable
      of eliciting a positive response in an extraordinarily wide range of biological
      and biochemical tests; among them tests for enzyme inhibition, fidelity of DNA
      synthesis, mutation, chromosome aberrations, cancer and birth defects. It reacts
      or complexes with many biomolecules and adversely affects the reproductive,
      nervous, gastrointestinal, immune, renal, cardiovascular, skeletal, muscular and
      hematopoietic systems as well as developmental processes. It is likely that lead
      is a selective agent that continues to act on and influence the genetic structure
      and future evolution of exposed plant and animal populations.

PMID- 9637234
TI  - Genetic, carcinogenic and teratogenic effects of radiofrequency fields.
AB  - This paper reviews the literature data on the genetic toxicology of
      radiofrequency (RF) radiation. Whereas in the past most studies were devoted to
      microwave ovens and radar equipment, it is now mobile telecommunication that
      attracts most attention. Therefore we focus on mobile telephone frequencies where
      possible. According to a great majority of the papers, radiofrequency fields, and
      mobile telephone frequencies in particular, are not genotoxic: they do not induce
      genetic effects in vitro and in vivo, at least under non-thermal exposure
      conditions, and do not seem to be teratogenic or to induce cancer. Yet, some
      investigations gave rather alarming results that should be confirmed and
      completed by further experiments. Among them the investigation of synergistic
      effects and of possible mechanisms of action should be emphasised.

PMID- 9637235
TI  - Teratogenic and reproductive effects of low-frequency magnetic fields.

PMID- 9637236
TI  - Animal and cellular studies on carcinogenic effects of low frequency (50/60-Hz)
      magnetic fields.

PMID- 9637237
TI  - Repair of DNA damage in mammalian cells after treatment with UV and dimethyl
      sulphate: discrimination between nucleotide and base excision repair by their
      temperature dependence.
AB  - Alkylating agents have been reported to give rise to both short and long patches
      of repair. The reason for the different patch sizes is not known. One possibility
      is that alkylating agents can trigger both base and nucleotide excision repair.
      Another possibility is that base excision repair itself can result in different
      patch sizes. Recognition and incision at lesions is the rate limiting step in
      excision repair. In order to discriminate between base and nucleotide excision
      repair it would be desirable to be able to distinguish between different incision
      activities. In order to accurately measure incision rates, the rejoining of the
      strand-breaks formed must be inhibited. We have used two inhibitors, aphidicolin
      and 3-aminobenzamide. Aphidicolin, an inhibitor of DNA polymerases
      alpha/delta/epsilon. caused accumulation of single-strand breaks both after UV
      and dimethylsulphate. 3-Aminobenzamide, an inhibitor of poly(ADP-ribose)
      polymerase caused accumulation of single-strand breaks only after alkylating
      agents and is thus specific for base excision repair. Enzymatic activities can be
      characterised by their activation energy. In order to discriminate between base
      and nucleotide excision repair the temperature dependence of incision activities
      was determined. When the temperature is decreased, the incision rate is reduced
      to a larger extent for UV than for DMS-induced repair. Incisions in UV-irradiated
      cells are practically cut off at temperatures of 15 degrees C and below, whereas
      DMS-exposed cells still are actively repairing at this temperature. In DMS
      treated cells the temperature dependence was the same whether aphidicolin or 3
      aminobenzamide was used, speaking against an involvement of nucleotide excision
      repair. In addition, cell lines deficient in nucleotide excision repair responded
      in the same way to aphidicolin after DMS treatment as normal cells and were able
      to make incisions at 15 degrees C. This indicates that nucleotide excision repair
      is not to any significant amount involved in repair of DNA damage induced by a
      methylating agent.

PMID- 9637238
TI  - Kinetics of DNA strand breaks and protection by antioxidants in UVA- or UVB
      irradiated HaCaT keratinocytes using the single cell gel electrophoresis assay.
AB  - The aim of this study was to characterize the genotoxic action of UVA and UVB in
      human keratinocytes by application of the single cell gel electrophoresis assay
      (SCGE assay). Dose dependence of DNA damage, the time course of its repair, and
      the influence of cellular antioxidant status were assessed. Irradiation with UVA
      or UVB both resulted in a dose-dependent increase in the level of DNA damage. A
      time course study to evaluate the repair kinetics in keratinocytes irradiated
      with 5 J/cm2 UVA revealed an immediate occurrence of DNA effects which
      subsequently disappeared within about 1 h, indicating removal of DNA lesions.
      This rapid repair of DNA damage is consistent with the observation that 5 J/cm2
      UVA did not impair cellular viability. In contrast, exposure to 15 mJ/cm2 UVB
      resulted in a prolonged repair of DNA damage which lasted about 25 h. Thus, the
      repair kinetics of UVA- and UVB-induced DNA damage clearly differed from each
      other, implicating the induction of different types of DNA lesions by UVA and
      UVB. Neither a pretreatment with Mg-ascorbyl phosphate or D,L-alpha-tocopherol,
      nor depletion of endogenous glutathione altered cellular sensitivity to UVB. In
      contrast, the DNA damaging effects of UVA could be counteracted by a pretreatment
      with these antioxidants. These observations confirm that the UVA-induced effects
      on DNA are related to radical mediated strand breaks and DNA lesions forming
      alkali-labile sites. The UVB-induced effects mainly occur as a consequence of
      excision repair-related strand breaks. The observed repair kinetics of DNA
      lesions and the influence of cellular antioxidant status may help to elucidate
      protective mechanisms against the carcinogenic effects of UV radiation present in
      sunlight.

PMID- 9637239
TI  - Repair in Escherichia coli alkB mutants of abasic sites and 3-methyladenine
      residues in DNA.
AB  - Escherichia coli alkB mutants are sensitive to methyl methanesulfonate and
      dimethylsulphate, and are defective in the processing of methylated DNA. The
      function of the AlkB protein has not been determined. Here, we show that alkB
      mutants are not defective in repairing several different types of potentially
      toxic DNA lesions that are known to be generated by MMS, including apyrimidinic
      and apurinic sites, and secondary lesions that could arise at these sites (DNA
      protein cross-links and DNA interstrand cross-links). Also, alkB mutants were not
      sensitive to MeOSO2-(CH2)2-Lex, a compound that alkylates the minor groove of DNA
      generating primarily 3-methyladenine.

PMID- 9637240
TI  - A novel plasmid shuttle vector for the detection and analysis of microsatellite
      instability in cell lines.
AB  - Microsatellite instability is an important feature of tumors from hereditary
      nonpolyposis colorectal carcinoma (HNPCC) patients as well as a variety of
      sporadic tumors. Here, we present a novel plasmid shuttle vector for the
      detection of this replication error (RER+) phenotype in human cell lines. The
      episomely replicated plasmid pZCA29 harbours the bacterial beta-galactosidase
      gene interrupted by two palindromically arranged poly-(CA)-repeat tracts. The
      resulting + 1-frameshift leads to white colonies of Escherichia coli DH10B on X
      Gal/IPTG1 agar plates. Mutations in the repeats characteristic of the RER+
      phenotype may result in the loss or gain of CA-repeats leading to blue bacterial
      colonies. We transiently transfected the colorectal cancer cell lines SW480 and
      HCT116 with the plasmid pZCA29, isolated replicated plasmid DNA after several
      days and used it to transform E. coli DH10B. We found 1.0 to 1.7% blue colonies
      after passage of the plasmid through the RER+-cell line SW480 in contrast to 3.5
      to 8.1% blue colonies after transfection of the RER+-cell line HCT116, the
      mutation frequencies increasing with incubation time. Sequence analysis of
      mutated plasmids revealed mostly 2-bp deletions which occurred especially in one
      of the repeat tracts. We conclude that pZCA29 appears to be a suitable shuttle
      vector for the detection and analysis of a RER+-phenotype in cell lines.

PMID- 9637241
TI  - Genotoxicity and mutagenicity of the alpha, beta-unsaturated carbonyl compound
      crotonaldehyde (butenal) on a plasmid shuttle vector.
AB  - Crotonaldehyde is an alpha,beta-unsaturated carbonyl compound and an important
      environmental and industrial toxic substance. Its mutagenic and carcinogenic
      properties are related to its reactivity to DNA, where it forms different guanine
      adducts. In order to study the mutagenic consequences of this agent in intact
      human cells, we treated the shuttle vector plasmid pZ189 with different doses of
      crotonaldehyde at 37 degrees C for 2 h and then transfected the such damaged
      plasmid into the normal human lymphoblast cell line GM0621. Within these host
      cells the guanine adducts are repaired and the plasmids replicated by cellular
      enzymes. After 2.5 days replicated plasmids were purified from the cells and
      plasmid survival was quantitated by transformation ability. With increasing doses
      of crotonaldehyde, we found a significant decline of plasmid survival, reflecting
      a pronounced genotoxicity of crotonaldehyde-induced DNA damage in intact human
      cells. Using the plasmid encoded mutagenesis marker gene supF, we were able to
      screen for mutants and determine mutation frequency in recovered plasmids. A
      significant increase in mutation frequency with increasing doses of
      crotonaldehyde reflects mutagenicity of crotonaldehyde-induced DNA damage. Base
      sequence analysis of recovered mutants revealed 39% point mutations, 46%
      deletions, and 15% insertions and inversions. Most of the point mutations (82%)
      were located at G:C base pairs, which is well explained by the DNA damage profile
      of crotonaldehyde. Among deletions we found a frequent reoccurrence of two hot
      spot deletions, representing 62% of all deletions. The sites of breakpoints of
      these deletions hot spots and of other deletions within the plasmid were also
      found to be sites of DNA breaks, directly induced by crotonaldehyde, as seen in
      an endlabeled plasmid fragment, treated with crotonaldehyde. Further analysis of
      the flanking sequences around the deletion breakpoints revealed a high frequency
      of four different kinds of short sequence homologies of up to eight base pairs.

PMID- 9637242
TI  - Genetic interactions between mutants of the 'error-prone' repair group of
      Saccharomyces cerevisiae and their effect on recombination and mutagenesis.
AB  - We have created an isogenic series of yeast strains that carry genetic systems to
      monitor different types of recombination and mutation [B. Liefshitz, A. Parket,
      R. Maya, M. Kupiec, The role of DNA repair genes in recombination between
      repeated sequences in yeast, Genetics 140 (1995) 1199-1211.]. In the present
      study we characterize the effect of mutations in genes of the 'error-prone' or
      postreplicative repair group on recombination and mutation. We show that rad5 and
      rad18 strains have elevated levels of spontaneous recombination, both of ectopic
      gene conversion and of recombination between direct repeats. The increase in
      recombination levels is similar in both mutants and in the rad5 rad18 double
      mutant, suggesting that the RAD5 and RAD18 gene products act together with
      respect to spontaneous recombination. In contrast, RAD5 and RAD18 play
      alternative roles in mutagenic repair: mutations in each of these genes elevate
      spontaneous forward mutation at the CAN1 locus, but when both genes are deleted,
      a low level of spontaneous mutagenesis is seen. The RAD5/RAD18 pathway of
      mutagenic repair is dependent on the REV3-encoded translesion polymerase. We
      analyze the interactions between the RAD5 and RAD18 gene products and other
      repair genes. The high recombination levels seen in rad5 and rad18 mutants is
      dependent on the RAD1, RAD51, RAD52, and RAD57 genes. The Srs2 helicase plays an
      important role in creating the recombinogenic substrate(s) processed by the RAD5
      and RAD18 gene products.

PMID- 9637243
TI  - Quantitative polymerase chain reaction assay for DNA repair within defined
      genomic regions.
AB  - We have developed a quantitative assay to determine repair of structurally
      different DNA lesions at defined genomic sites. This assay depends on the fact
      that many different types of damage are repaired by the same nucleotide excision
      repair (NER) pathway which includes synthesis of short DNA fragments at the sites
      of damage. After exposure to damaging agents, cells are treated with 5
      bromodeoxyuridine (BrdUrd) to label the regions undergoing repair with the
      presumption that regions that have been more efficiently repaired would
      incorporate more BrdUrd than regions that were less effectively repaired. Thus,
      the abundance of the different sequences in the BrdUrd-containing DNA would be a
      direct and quantitative measure for the repair rates of the corresponding
      regions. The BrdUrd-containing, repaired DNA was isolated by CsCl gradient
      centrifugation and immunoprecipitation with anti-BrdUrd antibody and was used as
      template in quantitative PCR in which the amount of the product was directly
      proportional to the amount of template. This approach was used to address the
      question whether DNA repair after UV-irradiation occurs in an uniform, random
      manner or with preferences for certain regions. We found out that there was a
      higher repair efficiency at the 5'-end of the mouse gamma-globin domain in
      Ehrlich ascites tumor cells.

PMID- 9637244
TI  - Altered UV resistance and UV mutational spectrum in repair-proficient murine
      fibroblasts expressing endonuclease V.
AB  - In previously reported studies, we transfected repair-proficient murine
      fibroblasts with the denV gene of bacteriophage T4 and showed that expression of
      encoded endonuclease V markedly enhanced cyclobutane pyrimidine dimer (CPD)
      repair and reduced the frequency of ultraviolet radiation (UV)-induced mutations.
      In the present studies, we compared the spectra of UV-induced mutations at the
      hprt locus in denV-transfected and control cells. A significant difference in
      mutation types was observed. While multiple base deletions and single base
      insertions were found in denV-transfected but not control cells, multiple tandem
      and non-tandem point mutations identified in control cells were absent in denV
      transfected cells. When we compared colony survival following UV exposure in the
      two cell lines, it appeared that endonuclease V expression did not enhance UV
      resistance, instead denV-transfected cells had increased susceptibility to low
      fluences of UV. The effects of endonuclease V expression on UV resistance and on
      UV mutational spectrum are likely to be due both to the removal of CPDs and to
      the novel enzymatic activity of endonuclease V.

PMID- 9637245
TI  - Activity of Escherichia coli DNA-glycosylases on DNA damaged by methylating and
      ethylating agents and influence of 3-substituted adenine derivatives.
AB  - Methylating and ethylating agents are used in the chemical industry and produced
      during tobacco smoking. They generate DNA base damage whose role in cancer
      induction has been documented. Alkylated bases are repaired by the base excision
      repair pathway. We have established the repair efficiency of methylated and
      ethylated bases by various Escherichia coli repair proteins, namely 3
      methyladenine-DNA-glycosylase I (TagA protein), which excises 3-methyladenine and
      3-methylguanine, 3-methyladenine-DNA-glycosylase II (AlkA protein), which has a
      broad substrate specificity including 3- and 7-alkylated purines and the
      formamidopyrimidine(Fapy)-DNA-glycosylase (Fpg protein) repairing imidazole ring
      opened 7-methylguanine. The comparison of the Km values of these various enzymes
      showed that methylated bases were excised more efficiently than ethylated bases.
      Several 3-alkyladenine derivatives have been synthesized and examined for their
      ability to inhibit the activity of the various repair proteins. We have shown
      that 3-ethyl-, 3-propyl-, 3-butyl- and 3-benzyladenine were much more efficient
      inhibitors of TagA protein than 3-methyladenine. The inhibitory effect was
      increased with the increase of the size of alkyl-group and IC50 for 3
      benzyladenine was 0.4 +/- 0.1 microM as compared to 1.5 +/- 0.3 mM for 3
      methyladenine. These compounds inhibited neither the AlkA protein nor human 3
      methyladenine-DNA-glycosylase (ANPG protein). Moreover, 3-hydroxyethyladenine did
      not affect the activity of any of these enzymes. Taken together, these results
      suggest that hydrophobic interactions are involved in the mechanism of inhibition
      and/or recognition and excision of alkylated purines by TagA protein.

PMID- 9637246
TI  - Requirement for DNA mismatch repair proteins in the transcription-coupled repair
      of thymine glycols in Saccharomyces cerevisiae.
AB  - Defects in DNA mismatch repair have been shown to lead to increased genomic
      instability and mutability. We recently found that human cells defective in the
      DNA mismatch repair gene, hMSH2, were deficient in the transcription-coupled
      repair (TCR) of both oxidative DNA damage, including thymine glycols, and UV
      induced DNA damage. However, in a hMLH1 mutant, only a reduction in the TCR of UV
      damage was observed. In this study, we examined whether TCR of thymine glycols in
      Saccharomyces cerecisiae also requires the genes involved in DNA mismatch repair.
      We found that yeast cells containing mutations in MSH2 were deficient in the
      removal of thymine glycols from the transcribed strand of the RPB2 gene, while
      cells with mutations in either MLH1 or PMS1 alone showed near normal levels of
      TCR of thymine glycols. Interestingly, double mutants in the MLH1 and PMS1 genes
      were deficient in TCR of thymine glycols. Taken together, these results suggest
      that these two MutL homologues can act independently of each other, but that they
      have overlapping roles in TCR. Overall levels of thymine glycol removal were not
      reduced in the mismatch repair mutants. In contrast to the results with thymine
      glycols, no defects in TCR of pyrimidine dimers were found in cells with
      mutations in MSH2, MLH1, PMS1, and MLH1/PMS1.

PMID- 9637247
TI  - Impaired DNA repair capacity in skin fibroblasts from various hereditary cancer
      prone syndromes.
AB  - Host-cell reactivation (HCR) of UV-C-irradiated herpes simplex virus type 1 (HSV
      1) has been determined in skin fibroblasts from the following hereditary cancer
      prone syndromes: aniridia (AN), dysplastic nevus syndrome (DNS), Von Hippel
      Lindau syndrome (VHL), Li-Fraumeni syndrome (LFS) and a family with high
      incidence of breast and ovarian cancer. Cells from AN, DNS or VHL patients were
      found to exhibit heterogeneity in HCR. Cells from individuals belonging to an LFS
      family show reduced HCR in all cases where the cells were derived from persons
      carrying one mutated p53 allele, whereas cells derived from members with two wild
      type alleles show normal HCR. LFS cells with reduced HCR also reveal reduced
      genome overall repair, and a slower gene-specific repair of the active adenosine
      deaminase (ADA) gene, but little if any repair of the inactive 754 gene. In the
      breast/ovarian cancer family, reduced HCR is observed in skin fibroblasts derived
      from both afflicted and unaffected individuals. In addition, these cells display
      lower survival after exposure to UV-C and exhibit higher levels of SCEs than
      those in normal cells. These observations indicate that various hereditary cancer
      prone syndromes, carrying mutations in different tumor-suppressor genes, exhibit
      an unexplained impairment of the capacity to repair UV-damaged DNA.

PMID- 9637248
TI  - Minimal tRNA(Ser) and tRNA(Sec) substrates for human seryl-tRNA synthetase:
      contribution of tRNA domains to serylation and tertiary structure.
AB  - The recognition process of tRNA(Ser) and tRNA(Sec) by human seryl-tRNA synthetase
      (SerRS) was studied using T7 transcripts representing defined regions of human
      tRNA(Ser) or tRNA(Sec) and the influence of the tRNA elements on serylation and
      tertiary structure was elucidated. The anticodon arms of both tRNAs showed no
      contribution to serylation in contrast to the acceptor stems and the long extra
      arms. D and T arms were only involved in formation of the L-shaped tRNA
      structure, not in the recognition process between tRNAs and SerRS. This is the
      first report of microhelices adapted from human tRNAs being aminoacylated by
      their homologous synthetase.

PMID- 9637249
TI  - P1,P4-diadenosine 5' tetraphosphate induces nitric oxide release from bovine
      aortic endothelial cells.
AB  - Since the infusion of P1,P4-diadenosine 5' tetraphosphate (Ap4A) into animal
      models induces vasodilation [1,2], the present study was performed to determine
      whether Ap4A induces the release of nitric oxide (NO) from endothelial cells.
      Ap4A induced NO release was 4.2-fold greater than the amount of NO released under
      basal condition. Ap4A induced NO release was inhibited by NG-nitro-L-arginine (L
      NNA) and this inhibition was reversed by L-Arg. In addition, EGTA inhibits Ap4A
      induced NO release. These data are consistent with Ap4A inducing the release of
      NO from endothelial cells through the activation of endothelial nitric oxide
      synthase.

PMID- 9637250
TI  - Quantitative structure activity relationships for the conversion of
      nitrobenzimidazolones and nitrobenzimidazoles by DT-diaphorase: implications for
      the kinetic mechanism.
AB  - Quantitative structure activity relationships (QSARs) for the conversion of
      nitrobenzimidazolones and nitrobenzimidazoles by rat liver DT-diaphorase (EC
      1.6.99.2) are described. The parameter used for description of the QSARs is the
      energy of the lowest unoccupied molecular orbital (E(LUMO)) of the nitroaromatic
      compounds. Interestingly, correlations with E(LUMO) were observed for both the
      natural logarithm of kcat, but also for the natural logarithm of kcat/Km. The
      minimal kinetic model in line with these QSARs is a ping-pong mechanism that
      includes a substrate binding equilibrium in the second half reaction.

PMID- 9637251
TI  - Human RanBP3, a group of nuclear RanGTP binding proteins.
AB  - A group of novel human Ran-binding proteins, RanBP3, was identified using the
      yeast two-hybrid system via Ran-mediated interaction with the nucleotide exchange
      factor RCC1. Several open reading frames, representing putative alternatively
      spliced products, were established by cDNA cloning. Two of them, RanBP3-a and
      RanBP3-b, encode nuclear hydrophilic proteins of 499 and 562 amino acid residues.
      The sequences contain FXFG motifs, characteristic of a subgroup of nucleoporins,
      and a C-terminal domain showing similarity to the Ran-binding protein RanBP1.
      These proteins are localized in the nucleus, preferentially bind RanGTP and may
      be nuclear effectors of the Ran pathway.

PMID- 9637252
TI  - Enhancement of transcriptional activity of T7 RNA polymerase by guanidine
      hydrochloride.
AB  - T7 RNA polymerase shows an increase in processive transcription in the presence
      of low concentrations of guanidine hydrochloride (GdnCl) upto 60 mM, which is not
      observed when the enzyme is treated with urea. Higher concentrations of the
      denaturant lead to a progressive loss in the processive transcriptional activity
      of the enzyme. We have attempted to explain the above phenomenon in terms of the
      structural change in the enzyme. Fluorescence and CD studies suggest that the
      tertiary structure of the native enzyme undergoes an alteration upon addition of
      low concentration of guanidine hydrochloride. This is also indicated from the
      decreased susceptibility of the enzyme to limited proteolysis by trypsin.

PMID- 9637253
TI  - Effect of oxygen free radicals on myosin in muscle fibres.
AB  - Experiments were performed on glycerol-extracted muscle fibres prepared from
      psoas muscle of rabbit in the presence of hydroxyl free radical generating
      system. Short irradiation of spin-labelled muscle fibres by UV light showed the
      interaction of probe molecules with oxygen free radicals. The intensity of the
      EPR signal from maleimide or isothiocyanate spin labels attached to the essential
      thiol groups decreased following irradiation. Oxygen free radicals affected the
      rate constant of the transition AM.ADP.Vi-->AM.ADP in the ATP hydrolysis cycle.
      It was found that the essential -SH groups of myosin were involved in the
      oxidation of sulphydryls by Ce(IV). Ce(IV) complexed to nitrilotriacetic acid in
      the presence of spin trap produced long-lived free radicals located partly on SH
      1 sulphydryls.

PMID- 9637254
TI  - Biological dynamics and distribution of 3-hydroxy fatty acids in the yeast
      Dipodascopsis uninucleata as investigated by immunofluorescence microscopy.
      Evidence for a putative regulatory role in the sexual reproductive cycle.
AB  - Dipodascopsis uninucleata has been recently shown to produce 3-hydroxy polyenoic
      fatty acids from several exogenous polyenoic fatty acids. In order to examine
      whether endogenous 3-hydroxy fatty acids (3-OH-FA) may be implicated in the
      developmental biology of this yeast, we mapped by immunofluorescence microscopy
      their occurrence in fixed cells with or without cell walls using an antibody
      raised against 3R-hydroxy-5Z,8Z,11Z,14Z-eicosatetraenoic acid (3R-HETE), the
      biotransformation product from arachidonic acid (AA). This antibody turned out to
      cross-react with other 3-OH-FA. 3-OH-FA were detected in situ in gametangia,
      asci, as well as between released ascospores, and proved to be associated with
      the sexual reproductive stage of the life cycle of the yeast. Acetylsalicylic
      acid (1 mM), which is known to suppress the formation of 3-OH-FA from exogenous
      polyenoic fatty acids, inhibited the occurrence of immunoreactive material as
      well as the sexual phase of the life cycle suggesting a prominent regulatory role
      of 3-OH-FA for the latter.

PMID- 9637255
TI  - Characterization of the 3' end of the mouse SERCA 3 gene and tissue distribution
      of mRNA spliced variants.
AB  - The sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) type 1 and 2 genes are
      alternatively spliced at their 3' end. We hypothesized that similar mechanism may
      occur for SERCA 3. Two spliced variants were identified by RNase protection
      analysis. We then isolated and sequenced the 3' end portion of the mouse SERCA 3
      gene, and confirmed the presence of an alternative mRNA transcript by sequencing
      a cDNA fragment obtained by RT-PCR. Tissue distribution of the alternatively
      spliced mRNAs was studied by RT-PCR: SERCA 3b was the only isoform expressed in
      endothelial cells from aorta and heart and also was the major isoform in lung and
      kidney whereas SERCA 3a and 3b were coexpressed in trachea, intestine, thymus,
      spleen, and fetal liver.

PMID- 9637256
TI  - Cdc42 is required for membrane dependent actin polymerization in vitro.
AB  - In vitro actin based motility assays with bacterial pathogens have provided
      powerful systems to both understand and dissect actin dynamics as well as cell
      motility. Taking advantage of endogenous membrane vesicles in Xenopus extracts we
      have developed an in vitro assay to study membrane dependent actin
      polymerization. Our results demonstrate that membrane dependent actin
      polymerization, in contrast to Listeria stimulated actin filament assembly, is
      dependent on small GTPases of the Rho family. Using a combination of depletion
      and reconstitution experiments we have shown that Cdc42 but not Rac or Rho is
      required to stimulate actin polymerization from membranes. The in vitro system we
      have described here is amenable to identification of the downstream effectors of
      Cdc42 required for membrane dependent actin polymerization.

PMID- 9637257
TI  - An intrinsically stable antibody scFv fragment can tolerate the loss of both
      disulfide bonds and fold correctly.
AB  - A fully functional cysteine-free derivative of the intrinsically stable anti-HER2
      scFv fragment hu4D5-8 was generated by replacing the disulfide forming cysteine
      residues in VH and VL with the amino acid combination valine-alanine in both
      domains. The antigen binding properties, determined by ELISA and BIAcore
      measurements, were not affected by removal of the disulfide bonds. The
      thermodynamic stability of the disulfide-containing scFv of 8.1 kcal/mol is
      decreased upon complete reduction of both disulfides to 2.7 kcal/mol, while that
      of the valine-alanine variant is somewhat higher (about 3.8 kcal/ mol). Our
      results suggest that, in principle, a disulfide-free fully functional derivative
      of any scFv can be obtained, as long as the corresponding disulfide-containing
      scFv has a high enough thermodynamic stability.

PMID- 9637258
TI  - Unique chemical reactivity of His-21 of CRM-197, a mutated diphtheria toxin.
AB  - CRM-197 is a mutated diphtheria toxin (63000 Da) widely used as a carrier protein
      of conjugated vaccines. Among the 14 histidines of CRM-197, His-21 was found to
      be modified selectively with iodoacetamide based reagents. This finding suggests
      a simplified method for the preparation of conjugate vaccines crosslinked to CRM
      197. A bifunctional iodoacetamide, N,N'-(2-hydroxy-1,3-propanediyl)-bis-12
      iodoacetamidel (I-CH2-CONH-CH2-CH(OH)-CH2-NHCO-CH2-I) (HPBIA), was synthesized
      and allowed to react with CRM-197. In the alkaline buffer of pH 8.0-8.4, HPBIA
      was shown to react and intra-bridge His-21 and Lys-24 of CRM-197 sequentially. At
      lower pH (7.1-7.5) in the phosphate buffer, the reactivity of Lys-24 toward HPBIA
      was suppressed drastically. Under these conditions, His-21 could be specifically
      labeled with HPBIA. Initial experiments have demonstrated that HPBIA modified CRM
      197 is able to crosslink to a cysteine-containing peptide. These results offer a
      potential route for improving the homogeneity of CRM-197 based protein-peptide as
      well as protein-polysaccharide conjugates.

PMID- 9637259
TI  - Lack of beta-amyloid production in M19 cells deficient in site 2 processing of
      the sterol regulatory element binding proteins.
AB  - The processing of the amyloid precursor protein (APP) and the sterol regulatory
      element binding protein show remarkable analogies. Following a first lumenal
      cleavage, both proteins undergo a cleavage within the transmembrane domain by
      enzymatic activities named gamma-secretase and S2P, respectively. We analyzed the
      processing of APP in the mutant Chinese hamster ovary (CHO) cell line M19 which
      lacks the S2P gene encoding for a putative metalloprotease. In these cells, we
      were not able to detect any beta-amyloid production from endogenous or
      transiently overexpressed APP, although the transport of APP along the secretory
      pathway, its processing by alpha- and beta-secretase, as well as its secretion
      were normal. This strongly suggests that the gamma-secretase cleavage in M19
      cells is severely impaired.

PMID- 9637260
TI  - Distinct phospholipase C-regulated signalling pathways in Swiss 3T3 fibroblasts
      induce the rapid generation of the same polyunsaturated diacylglycerols.
AB  - Prostaglandin F2alpha, platelet-derived growth factor (PDGF) and calcium
      ionophore A23187 stimulated the rapid (within 25 s) generation of polyunsaturated
      1,2-diacylglycerol (DAG) species, in particular 18:0/20:3n-9, 18:0/20:4n-6 and
      18:0/20:5n-3, in Swiss 3T3 fibroblasts. This was followed by a second sustained
      phase characterised by saturated, monounsaturated and diunsaturated DAG species
      derived, at least partially, from a phospholipase D/phosphatidate
      phosphohydrolase-linked pathway. This could be directly activated by phorbol
      ester. Assay of rat brain protein kinase C (PKC) in lipid vesicles showed that
      first phase, polyunsaturated-enriched DAG isolated from Swiss 3T3 cells was a
      more potent activator of kinase activity compared to that achieved with DAG from
      control or 5 min stimulated cells. Thus activation of distinct members of the
      phospholipase C family leads to the rapid and almost identical generation of
      polyunsaturated DAG species which are capable of preferentially activating
      protein kinase C (PKC).

PMID- 9637261
TI  - Identification of lysine-238 of Escherichia coli biotin carboxylase as an ATP
      binding residue.
AB  - Escherichia coli biotin carboxylase was affinity labeled with adenosine
      diphosphopyridoxal to identify its ATP binding site. Lysyl endopeptidase
      digestion of the modified protein, followed by high performance liquid
      chromatography separation and amino acid sequencing allowed to identify lysine
      238 to be the site of modification. Site-directed mutagenesis of this residue
      into alanine, arginine or glutamine resulted in mutants with much decreased
      activity. Lysine-238 seems to interact with the gamma-phosphate group of ATP but
      is not involved in catalysis.

PMID- 9637262
TI  - Imidazolium crosslinks derived from reaction of lysine with glyoxal and
      methylglyoxal are increased in serum proteins of uremic patients: evidence for
      increased oxidative stress in uremia.
AB  - Glyoxal (GO) and methylglyoxal (MGO) are reactive dicarbonyl compounds formed
      during autoxidation of both carbohydrates and lipids. They may react with lysine
      and arginine residues of proteins in Maillard or browning reactions, yielding
      advanced glycation or lipoxidation end products. Among these are the imidazolium
      crosslinks, N,N(-di(N(epsilon)-lysino))imidazolium (glyoxal-lysine dimer, GOLD)
      and N,N(-di(N(epsilon)-lysino))-4-methyl-imidazolium (methylglyoxal-lysine dimer,
      MOLD). We have detected and measured GOLD and MOLD in human serum by electrospray
      ionization/mass spectrometry/mass spectrometry (ESI/MS/MS), using 15N4-GOLD and
      15N4-MOLD as internal standards. In this report we show that levels of GOLD and
      MOLD are significantly elevated (3-4-fold, P< 0.01) in sera of non-diabetic
      uremic patients, compared to age-matched controls, and represent a major class of
      non-enzymatic, Maillard reaction crosslinks in plasma proteins. These results
      provide strong evidence for increased non-enzymatic crosslinking of tissue
      proteins by GO and MGO in uremia, implicating oxidative stress and resultant
      advanced glycation and lipoxidation reactions in tissue damage in uremia.

PMID- 9637263
TI  - Epstein-Barr virus strain characterization.
AB  - The Epstein-Barr virus (EBV), a ubiquitous human herpesvirus originally described
      in cultured lymphoblasts from African Burkitt's lymphoma, is the causative agent
      of infectious mononucleosis, but appears to be involved in the pathogenesis of a
      variety of diseases. EBV has the ability to establish lifelong persistent
      infection, where only a restricted pattern of the viral proteins is expressed.
      Periodic reactivation of EBV occurs, where mature EBV particles are produced.
      Strain variation is potentially important in the biology and epidemiology of EBV,
      and in attempts to relate EBV to associated diseases. Analysis of the EBV genomes
      isolated from patients with EBV-associated diseases and from various parts of the
      world has so far failed to identify conclusive disease-specific viral subtypes.
      This review focuses on the different strategies which have been used for strain
      characterization or subtyping of EBV.

PMID- 9637264
TI  - Clinical microbiology laboratories do not always detect resistance of Haemophilus
      influenzae with disk or tablet diffusion methods. Finnish Study Group for
      Antimicrobial Resistance (FiRe).
AB  - The performance of disk diffusion testing of Haemophilus influenzae was evaluated
      in 20 laboratories. Thirteen disk-medium-breakpoint-inoculum modifications were
      used in Finnish clinical microbiology laboratories. The performance of various
      methods was evaluated by testing a susceptible control strain and one with non
      beta-lactamase-mediated ampicillin resistance 10 times in 16 laboratories. Gaps
      in millimeters were measured between these two groups of results. The strains
      were separated by a gap of at least 5 mm in 8/16 laboratories testing ampicillin,
      in 7/15 laboratories testing cefaclor, in 5/ 16 laboratories testing cefuroxime,
      and in 15/16 laboratories testing trimethoprim-sulfa. Detection of ampicillin
      resistance was better with 2.5 microg tablets than with 10 microg disks or 33
      microg tablets. For MIC-determinations, 785 isolates and their disk diffusion
      results were collected. None of the 12 clinical isolates with non-beta-lactamase
      mediated ampicillin resistance was detected as resistant in the participating
      laboratories. The ampicillin and cefaclor results of the isolates were no better
      even when a laboratory was able to separate the control strains. Cefaclor results
      were unreliable because of poor disk diffusion-MIC correspondence and incoherent
      breakpoint references. Interlaboratory variation of the zone diameters caused
      false intermediate results of cefuroxime-susceptible strains. When ampicillin,
      cefaclor and cefuroxime were tested, the discrimination of laboratories using
      disks and tablets was equal, whereas the laboratories using paper disks were
      better able to detect trimethoprim-sulfa resistance.

PMID- 9637265
TI  - Adherence of Staphylococcus aureus, Klebsiella pneumoniae and Candida albicans to
      human buccal epithelial cells, from healthy persons and HIV carriers, under the
      influence of Broncho Vaxom in vitro and ascorbic acid in vivo.
AB  - We examined the in vitro effect of Broncho Vaxom (BV) (an immunobiotherapeutic
      preparation containing a lysate made from bacteria often involved in respiratory
      tract infections) on adherence of Staphylococcus aureus, Klebsiella pneumoniae
      and Candida albicans to human buccal epithelial cells (BEC) of healthy volunteers
      and HIV carriers. We also examined the ex vivo effect of ascorbic acid on the
      adherence of the same microorganisms to BEC of HIV carriers. The study reached
      the following conclusions: The presence of BV in vitro significantly reduces the
      adherence of the tested strains to BEC from healthy persons and HIV carriers. No
      significant difference was observed between healthy persons and HIV carriers
      regarding the adherence of the tested strains to BEC. Significant difference in
      the adherence of the tested strains to BEC was observed between HIV carriers who
      had been taking ascorbic acid over a 3-month period and those who had not. There
      was no further reduction in the adherence of the tested strains to BEC from HIV
      carriers who had been taking ascorbic acid in the presence of BV in vitro.

PMID- 9637266
TI  - Expression of bcl-2 in fetal thymus, thymomas and thymic carcinomas. Association
      with p53 expression and review of the literature.
AB  - Bcl-2 is a proto-oncogene inhibiting apoptosis, and p53 is a tumor supressor gene
      which induces apoptosis. Both seem to take part in tumorigenesis. An inverse
      relationship between the two genes has been reported in some neoplasms, although
      the exact mechanism is not fully understood. We have analyzed the expression of
      bcl-2 and p53 in 18 fetal thymuses and 18 clinically benign and malignant
      thymomas: bcl-2 was expressed by most medullary lymphocytes and epithelial cells
      of the normal thymus; p53 was not expressed at all. Bcl-2 and p53 were co
      expressed in the majority of the thymomas and the staining reaction was stronger
      in the clinically malignant ones. It is concluded that although co-expression of
      bcl-2 and p53 is of doubtful prognostic relevance, the staining pattern of bcl-2
      supports the histogenetic classification system of Muller-Hermelink.

PMID- 9637267
TI  - Ribotyping of Pseudomonas aeruginosa from infected patients: evidence of common
      strain types.
AB  - Sixty-nine strains of Pseudomonas aeruginosa isolated from infected patients at
      three hospitals in Valencia were serotyped and analyzed by comparison of
      restriction fragment length polymorphisms of ribosomal RNA genes (ribotyping).
      Genomic Southern blots of EcoRI restriction digests were hybridized with a
      universal rRNA gene probe from Escherichia coli 16S and 23S rRNA. Strains were
      genetically diverse and 12 different ribotypes of 2 to 7 bands between 5 and 21.5
      kb were defined. All strains shared a common band of 6.0 kb. The predominant
      ribotypes were R1 and R2, representing 25% and 41% of all isolates, respectively.
      Ribotypes were not consistently associated with serotypes, but they clearly
      subtyped strains of the same serotype. This study demonstrated the prevalence of
      certain strain types associated with infected patients at Valencia hospitals,
      confirming the high typability and reproducibility of a single enzyme ribotyping
      for epidemiological studies of Pseudomonas aeruginosa. Ribotyping could be
      particularly useful if used in conjunction with serotyping.

PMID- 9637268
TI  - Immunohistochemical determination of tumor angiogenesis measured by the maximal
      microvessel density in human prostate cancer.
AB  - Tumor growth beyond a certain size requires angiogenesis. Experimental evidence
      shows that once tumors leave the pre-angiogenic phenotype to become angiogenic,
      metastases often start to evolve. The aim of this study was to develop a
      reproducible immunohistochemical technique and method to characterize the
      neovascularization in archival prostate cancer tissue by quantifying the
      microvessel density (MVD). Archival tumor specimens from 64 consecutively
      diagnosed prostate cancer patients were immunostained for von Willebrand Factor
      (vWF), endothelial antigen and for CD31 combined with the use of different
      digestive enzymes (trypsin and pronase) and heating in a microwave oven. Both the
      mean and the maximal MVD, and the reproducibility of the method were estimated.
      Finally, the mean MVD, the maximal MVD, and clinical characteristics were
      correlated with the crude survival of the patient population. The
      immunohistochemical staining for vWF to measure the maximal MVD was found to be a
      reproducible method of characterizing the individual tumor. Both a univariate and
      a multivariate analysis demonstrated that the maximal MVD, in contrast to the
      mean MVD, was significantly associated with survival in prostate cancer patients.
      We conclude that evaluation of angiogenesis by immunostaining the endothelial
      cells for vWF measured by the MVD in the most vascularized areas of the tumor is
      a reproducible method of characterizing the individual prostate tumor. Maximal
      MVD proved to be an independent prognostic parameter useful in conjunction with
      other known prognostic markers in human prostate cancer.

PMID- 9637269
TI  - HIV infection in the first heart transplantation in Italy: fatal outcome. Case
      report.
AB  - A 46-year-old man with alcoholic dilated cardiomyopathy underwent heart
      transplantation on November 14, 1985. It was the first cardiac transplant in
      Italy and at that time no HIV antibody screening test was available in this
      country. The patient remained in good health for 6 years postoperatively, with
      only one episode of rejection (type 3A). In June 1992 he died of fulminant
      complications of AIDS and severe chronic rejection. Neither the patient nor the
      organ donor belonged to any of the known risk groups for HIV infection; a
      retrospective analysis revealed that perioperative blood transfusions had been
      the vectors of transmission.

PMID- 9637270
TI  - Experimental porcine neosporosis.
AB  - Six gilts were inoculated intramuscularly with 2.5x10(6) tachyzoites of Neospora
      caninum on three different days of gestation to study the pathogenic effect of
      Neospora infection in pigs, including possible transplacental transmission. The
      gilts were euthanized 59, 30, and 9/10 days postinoculation (p.i.), corresponding
      to days 107, 102/106 and 110/111 of pregnancy. With the exception of one animal
      (euthanized day 9 p.i.) all gilts seroconverted as measured by the indirect,
      fluorescent antibody test (IFAT). Neosporosis with multifocal intralobular
      necrotizing hepatitis was seen in the two gilts inoculated 9/10 days before
      euthanasia. The uterus of one gilt inoculated 59 days before euthanasia revealed
      granulomatous and focal necrotizing endometritis with a corresponding multifocal
      necrosis of the trophoblasts of two fetuses. Transplacental neosporosis was
      indicated in the two fetuses by strongly elevated Neospora IFAT titres in pleural
      fluid and by the presence of multifocal necrotizing encephalitis and hepatitis
      together with non-suppurative myocarditis, pneumonitis, nephritis and hepatitis.
      Furthermore, N. caninum was re-isolated in cell culture from one of these
      fetuses. A third fetus from the same gilt revealed only disseminated, pinpoint
      necroses in the liver. Immunohistochemically, N. caninum tachyzoites were
      detected in association with histopathological changes in the liver and the
      endometrium of the gilts, and in the brain, liver, and allantochorion of the
      three fetuses.

PMID- 9637271
TI  - Identification of Prototheca from bovine mastitis in Denmark.
AB  - In the present study, algal isolates recovered during the period 1991 through
      1996 from Danish cases of bovine mastitis were characterized and identified.
      Sixteen isolates of Prototheca were obtained, all of which were identified as
      Prototheca zopfii according to assimilation pattern, absence of capsules and
      resistance to clotrimazole.

PMID- 9637272
TI  - Immunoreactivity of pleural malignant mesotheliomas to glutathione S
      transferases.
AB  - Malignant mesotheliomas show a highly variable aggressiveness, but it is
      difficult to predict the outcome in the individual case at the time of diagnosis.
      Glutathione S-transferases are detoxification enzymes that have been correlated
      with the prognosis in some tumours. We have therefore assessed the value of GST
      expression as a prognostic parameter in mesotheliomas. The reactivities to GST
      pi, -alpha and -mu antibodies were studied in histological sections from
      altogether 88 cases. Most of them showed distinct cytoplasmic reactivity to one
      or more of the GST antibodies tested. This high prevalence is in good agreement
      with the low responsiveness of mesotheliomas to chemotherapy. However, there was
      no prognostic value in detecting GST immunoreactivity, and it gave no information
      of value for distinguishing between neoplastic and reactive mesothelium.

PMID- 9637273
TI  - A histomorphometric study of haematological disorders with respect to marrow
      fibrosis and osteosclerosis.
AB  - A retrospective investigation of 75 EDTA-decalcified Jamshidi biopsies collected
      over a 2-year period at Aarhus University Hospital was performed. The biopsies
      originated from 75 patients suffering from idiopathic myelofibrosis, other
      chronic myeloproliferative disorders, or other conditions with known associations
      with bone marrow fibrosis. The relative volumes of trabecular and woven bone, as
      well as haematopoietic and non-haematopoietic tissue, were estimated
      histomorphometrically. The degree of fibrosis was estimated semiquantitatively.
      Finally, the thickness of trabecular osteons was estimated from the number of
      lamellae by counting. Patients with idiopathic myelofibrosis had statistically
      significantly more bone tissue than the other groups of patients. The
      osteosclerosis was primarily due to woven bone. Larger cancellous osteons also
      suggested a positive balance in bone remodelling. The amount of bone tissue
      showed furthermore a statistically significant increase through the groups of
      polycythaemia vera, essential thrombocythaemia, chronic myelogenous leukaemia and
      idiopathic myelofibrosis. Parallel to the increase in the amount of bone, an
      increase in the degree of marrow fibrosis was detected. The positive correlation
      between the amount of bone and the degree of marrow fibrosis was statistically
      highly significant (p=0.0008).

PMID- 9637274
TI  - Evaluation of infectious etiology in subacute thyroiditis--lack of association
      with coxsackievirus infection.
AB  - The etiology of subacute granulomatous thyroiditis (SAT) is obscure, although it
      is postulated to be associated with viral infections and genetic factors. In the
      present study, the possibility of an infectious etiology was prospectively
      studied in 27 consecutive patients with SAT. Special emphasis was put on the role
      of enteroviruses. Coupled sera (interval one month) were taken from all patients
      and single sera from 29 control subjects for virus antibody determinations. Stool
      samples were collected for virus isolation and fine-needle aspiration samples
      from thyroid gland for the detection of enterovirus RNA using RT-PCR were taken
      from SAT patients. Enteroviral antibodies were tested using three different
      methods: indirect EIA, heavy chain capture RIA, and standard complement fixation
      (CF) test. Antibodies against other common viral pathogens, including
      enteroviruses, were screened using the CF test and those against Mycoplasma
      pneumoniae and Chlamydia pneumoniae using EIA and microimmunofluorescence
      techniques, respectively. Common respiratory viruses were also screened from
      nasopharyngeal suction samples by antigen detection EIA. Based on serological
      findings, one patient had acute Cytomegalovirus infection. All other patients
      were negative in antibody tests, virus isolation, RT-PCR, and antigen detection.
      Enterovirus RNA was not detected by PCR in the thyroid tissue in any of the fine
      needle aspiration samples. There was no evidence of recent enteroviral infections
      in SAT patients. The results suggest that SAT is not usually associated with
      acute infections. No evidence was obtained to support the proposed role of
      enteroviruses as an important etiologic agent of SAT.

PMID- 9637275
TI  - Radionuclide cancer therapy.
AB  - Therapeutic nuclear medicine is rapidly developing as an additional treatment
      modality in oncology. Its unique characteristics are the systemic, yet selective
      delivery of radiation doses in target tissues, its non-invasiveness, the relative
      lack of immediate and late side effects, and the advantage that uptake and
      retention in the tumor can be pre-assessed by tracer studies. Many different
      tumor seeking radiopharmaceuticals are being used for therapy by different routes
      and a variety of targeting mechanisms. The current clinical role of radionuclide
      therapy is briefly reviewed, as well as more general aspects and considerations,
      such as mechanisms for tumor targeting, the choice of radionuclide labels,
      radiopharmacy, drug delivery, radiation protection, dosimetry and toxicity.

PMID- 9637276
TI  - Rapid data acquisition protocol in ECG-gated myocardial perfusion SPECT with Tc
      99m-tetrofosmin.
AB  - Into 25 patients with heart disorders, 99mTc-tetrofosmin 555-740 MBq was injected
      intravenously at rest. After 40 minutes, ECG-gated myocardial perfusion SPECT was
      performed with a two detector gamma camera VERTEX (ADAC), setting up two
      detectors to form a 90-degree angle. Sixteen frames per R-R interval were
      acquired during a 180 degree rotation from the RAO 45 degrees to the LPO 45
      degrees. A pair of data sets with standard (SDA) and rapid data acquisition (RDA)
      protocols was collected. In an SDA protocol, SPECT imaging was performed for 50
      sec per step in 5 degree angular steps (total acquisition time; 15 minutes). An
      RDA protocol was conducted with 12 sec per step, 6 degree angular steps
      (acquisition time, 3 minutes). LVEF (%) and LVEDV (ml) quantitated automatically
      with a QGS program showed excellent correlations between two protocols with
      correlation coefficients of 0.980 (p < 0.01) and 0.983 (p < 0.01), respectively.
      Subsequently visual assessment of regional wall motion based on a four-point
      grading system was carried out with a 3-D cine LV display. High complete
      agreement was gained with 158 (90.3%) out of total 175 segments, so that
      assessment of the global and regional LV function with the RDA protocol
      demonstrated high reliability and feasibility.

PMID- 9637277
TI  - The evolutional stage changes in sarcoidosis on gallium-67 scintigraphy.
AB  - Gallium-67 scintigraphy has been proven as the imaging modality of choice in
      monitoring the presence of active disease in sarcoidosis. The purpose of this
      study is to analyze the patterns of evolutional stage changes of sarcoidosis
      while on steroid therapy by Ga-67 scintigraphy. METHODS: Eighty-six consecutive
      patients with biopsy-proved sarcoidosis are evaluated by Ga-67 scintigraphy.
      Thirty-six of 86 patients have had a baseline and one to eight follow-up Ga-67
      scintigraphs (total 136 studies). The initial follow-up scintigraphs are obtained
      on average about 4-12 months after the baseline study. RESULTS: Seventeen of 36
      patients (47.2%) are in stage IV at the time of the baseline study. Following
      their first course of corticosteroid therapy, 13 patients remained in the same
      stage and activity distribution pattern while 13 patients have shown reversion to
      other stages, eight patients showed complete remission while two patients became
      active from inactive stage. CONCLUSION: Evolutional stage changes are seen in 23
      patients (63.9%), including eight patients (22.2%) who showed complete
      scintigraphic remission. The evolutionary stage changes remain quite variable and
      unpredictable. This, however, should not detract from the usefulness of Ga-67
      scintigraphy in the diagnosis and prognostic evaluation of sarcoidosis,
      particularly when extrapulmonary involvement (Stage IV disease) is present.

PMID- 9637278
TI  - Localization of colorectal carcinoma by rhenium-188-labeled B72.3 antibody in
      xenografted mice.
AB  - In order to evaluate the feasibility of 188Re-labeled antibodies for
      radioimmunotargeting, monoclonal antibody B72.3, recognizing TAG-72, expressed on
      the surface membranes of colorectal cancer cells, was directly labeled with
      188Re, obtained from a 188W/188Re generator, using stannous tartrate and compared
      with 125I-labeled B72.3. As a control, a human IgG was also radiolabeled with
      188Re and 125I. Prepared antibodies for 188Re labeling could be stored as kits.
      Biodistribution was determined in nude mice inoculated with human colorectal
      carcinoma LoVo. Labeling efficiency and immunoreactivity of 188Re-B72.3 were
      80.3% and 64.7%, respectively. 188Re-B72.3 localized specifically in the LoVo
      tumors. Although the absolute tumor accumulation level of 188Re-B72.3 was lower
      than 125I-B72.3, 188Re-B72.3 demonstrated higher tumor-to-blood contrast than the
      125I-labeled counterpart, 2.04 +/- 0.44 vs. 1.05 +/- 0.28 at 96 hours, because of
      fast clearance from the blood. 188Re-B72.3 seemed efficient for the imaging and
      therapy of colorectal carcinoma.

PMID- 9637279
TI  - Clinical significance of reduced cerebral metabolism in multiple sclerosis: a
      combined PET and MRI study.
AB  - Magnetic resonance imaging (MRI) in patients with multiple sclerosis (MS) has
      provided major insights into the disease's natural history, and many studies have
      focussed on possible correlations between MRI findings and the clinical
      manifestations of MS. In contrast, there are few reports on possible
      relationships between functional imaging data and cognitive function. The present
      study assessed the relationship between clinical presentation and combined
      anatomical and functional imaging data in MS. Twenty patients with definite MS
      underwent MRI and positron emission tomography (PET) to evaluate cerebral blood
      flow (rCBF) and oxygen metabolism (rCMRO2). The relationships between these
      neuroimaging findings and clinical data, including the Expanded Disability Status
      Scale (EDSS), Mini-mental status scale, Hasegawa Dementia Scale and relapse time,
      were evaluated with Spearman's rank correlation coefficients. A general reduction
      in rCBF and rCMRO2 in the gray and white matter were found in the MS patients.
      EDSS was correlated with the number and size of the lesions on MRI and was
      negatively correlated with rCMRO2. A correlation between the decrease in rCMRO2
      and the level of cognitive impairment was also found. The severity of cerebral
      hypometabolism was also related to the number of relapses. Morphological and
      functional findings obtained by MRI and PET are closely related to the clinical
      status in MS. Our results suggest that measurement of cerebral metabolism in MS
      has the potential to be an objective marker for monitoring disease activity and
      to provide prognostic information.

PMID- 9637280
TI  - Myocardial glucose metabolism in patients with hypertrophic cardiomyopathy:
      assessment by F-18-FDG PET study.
AB  - In an investigation of myocardial metabolic abnormalities in hypertrophic
      myocardium, the myocardial glucose metabolism was evaluated with F-18
      fluorodeoxyglucose (FDG) positron emission tomography (PET) in 32 patients with
      hypertrophic cardiomyopathy, and the results were compared with those in 9
      patients with hypertensive heart disease. F-18-FDG PET study was performed in the
      fasting and glucose-loading states. The myocardial regional %dose uptake was
      calculated quantitatively. The average regional %dose uptake in the fasting state
      in the patients with asymmetric septal hypertrophy and dilated-phase hypertrophic
      cardiomyopathy was significantly higher than that in the patients with
      hypertensive heart disease (0.75 +/- 0.34%, 0.65 +/- 0.25%, and 0.43 +/-
      0.22%/100 g myocardium, respectively). In contrast, the average %dose uptake in
      the glucose-loading state in the patients with asymmetric septal hypertrophy and
      dilated-phase hypertrophic cardiomyopathy was not significantly different from
      that in patients with hypertensive heart disease (1.17 +/- 0.49%, 0.80 +/- 0.44%
      and 0.99 +/- 0.45%, respectively). The patients with apical hypertrophy had also
      low %dose uptake in the fasting state (0.38 +/- 0.21%) as in the hypertensive
      heart disease patients, so that the characteristics of asymmetric septal
      hypertrophy and dilated-phase hypertrophic cardiomyopathy are considered to be
      high FDG uptake throughout the myocardium in the fasting state. Patients with
      apical hypertrophy are considered to belong to other disease categories
      metabolically. F-18-FDG PET study is useful in the evaluation of the
      pathophysiologic diagnosis of patients with hypertrophic cardiomyopathy.

PMID- 9637281
TI  - Gallium-67 scintigraphy in the treatment and prognosis of acute adult T-cell
      lymphoma.
AB  - The case of a 77-year-old male patient who complained of left upper quadrant pain
      and progressive vomiting. Laboratory examination showed extremely high lactic
      acid dehydrogenase (LDH) and adult T-cell leukemia antibody (ATLA). The
      anatomical studies CT, MRI, US and upper GI series substantiated an omental
      lymphadenopathy which was causing a circumferential compression of portions of
      the duodenum and jejunum. Gallium-67 citrate (Ga-67) scintigraphy showed high
      uptake at LUQ. Ultrasound guided biopsy failed to confirm the diagnosis.
      Irradiation was performed. Ga-67 scintigraphy had a contributory role in clinical
      subtyping of the disease, planning of treatment, posttreatment assessment and
      prognostication of adult T-cell lymphoma.

PMID- 9637282
TI  - Spectral analysis applied to dynamic single photon emission computed tomography
      studies with N-isopropyl-p-(123I)iodoamphetamine.
AB  - This study was performed to evaluate the usefulness of spectral analysis (SA)
      applied to dynamic single photon emission computed tomography studies with N
      isopropyl-p-(123I)iodoamphetamine (IMP). The unidirectional clearance of IMP from
      the blood to the brain tissue (K1) obtained by SA (y (ml/g/min)) agreed well with
      that obtained from a two-compartment model using the nonlinear least-squares
      (NLSQ) method (x (ml/g/min)) (y = 0.994x + 0.003, r = 0.999, standard error of
      the estimate (SEE) = 0.005 ml/g/min). The rate constant for back diffusion of IMP
      from the brain tissue to the blood (k2) obtained by SA (y (min(-1))) also agreed
      well with that obtained by the NLSQ method (x (min(-1))) (y = 0.985x + 0.000, r =
      0.948, SEE = 0.001 min(-1)). The brain vascular volume (V0) obtained by SA (y
      (ml/g)) correlated well with that obtained by the NLSQ method (x (ml/g)) (y =
      1.138x + 0.000, r = 0.867, SEE = 0.012 ml/g). These results indicate that SA is
      applicable and useful for quantification of the kinetic parameters of IMP in the
      human brain, and can be an alternative approach to compartment analysis.

PMID- 9637283
TI  - Imaging of intraperitoneal tumors with technetium-99m GSA.
AB  - 99mTc labeled galactosyl serum albumin (GSA) has been used clinically as a
      receptor-binding agent for the assessment of liver function. The aim of this
      study was to investigate the usefulness of 99mTc-GSA in intraperitoneal (i.p.)
      tumor imaging. A tumor model was established by i.p. inoculating nude mice with
      human ovarian cancer cell SHIN-3, or colon cancer cell LS 180. Radiolabels were
      i.p. injected into the tumor-bearing mice and the biodistribution of
      radioactivity was examined. After administration, 99mTc-GSA rapidly accumulated
      in the tumor. The tumor uptake was 5.82-8.46 %ID/g from 30 min to 6 h after the
      injection. Radioactivity in the blood was very low, less than 0.3 %ID/g,
      resulting in high tumor-to-blood ratio. Tumors could be clearly seen by
      scintigraphic imaging. Accumulation of i.p.-injected 99mTc labeled human serum
      albumin (HSA) in i.p. tumors was similar to that of 99mTc-GSA, but radioactivity
      of 99mTc-HSA in the circulation was high, resulting in a significantly lower
      tumor-to-blood ratio. In conclusion, 99mTc-GSA, when i.p. injected, accumulated
      in i.p. tumors and cleared from circulation rapidly, which would make it useful
      for the imaging of i.p. tumors.

PMID- 9637284
TI  - Data base and management system for clinical positron emission tomography (PET)
      studies.
AB  - A data base and management system connected to an image analysis system has been
      developed and utilized for clinical positron emission tomography (PET). This data
      base system, 1) is based on "GBASE", a general purpose data base, which runs on a
      UNIX work station, 2) works on a network file system and is connected to PET
      cameras and other data acquisition devices as well as to an image analysis system
      "Dr.View", 3) centrally manages the data stored in a data storage unit, 4) is
      easily modifiable and expandable, and 5) has a human friendly interface which
      requires minimum operation for registration, retrieval and management. We have
      been using this system to handle clinical PET data for seven years and have
      optimized the data base schema. As a result, this system has become a truly
      practical tool for the daily operation and is well-received by technologists,
      nuclear physicians and attending physicians.

PMID- 9637285
TI  - Differences in intestinal length between specific-pathogen-free (SPF) and
      conventional swine.
AB  - The length of the small intestine, cecum, and the rest of the large intestine of
      specific-pathogen-free (SPF) swine was compared with that of conventional swine.
      The average length of the small intestine of SPF swine was shorter than that of
      conventional swine. The difference was significant for female SPF swine. There
      was no difference between SPF and conventional swine in the length of the cecum,
      colon and rectum.

PMID- 9637286
TI  - Expression of growth factor ligand and their receptor mRNAs in bovine ova during
      in vitro maturation and after fertilization in vitro.
AB  - We analyzed the expression of mRNAs for growth factor [epidermal growth factor
      (EGF), insulin-like growth factor-I (IGF-I), basic fibroblast growth factor
      (bFGF) and platelet-derived growth factor A chain (PDGF-A)] and their receptor
      (R) by reverse transcription-polymerase chain reaction in bovine ova during
      oocyte maturation in vitro (0-21 hr) and after fertilization in vitro (6-144 hr:
      zygotes to blastocysts). Transcripts for EGF were not found before fertilization.
      Transcripts for IGF-I were present in immature oocytes immediately after
      collection and in embryos from the 2-cell stage onward. Transcripts for bFGF were
      present in all stages of oocyte maturation and after fertilization up to the 16
      cell stage. Transcripts for PDGF-A were present in all stages of oocyte
      maturation and after fertilization up to the 2-cell stage. Transcripts for ErbB3
      (a member of the EGF-R subfamily), and bFGF-R were present in all stages of
      oocyte maturation, after fertilization up to the 2-cell stage, and the blastocyst
      stage. Transcripts for IGF-I-R and PDGF-Ralpha were present in all stages of
      oocyte maturation and embryo development. The results of this study showed that
      eight different messages for growth factor and their receptor were detectable in
      bovine ova during oocyte maturation and/or after fertilization in vitro and their
      expression patterns were the gene-specific rather than the developmental stage of
      bovine ova.

PMID- 9637287
TI  - Dual infection with enterotoxigenic Escherichia coli and porcine reproductive and
      respiratory syndrome virus observed in weaning pigs that died suddenly.
AB  - Diarrhea, sudden death after short duration of diarrhea and sudden death without
      apparent signs were observed in a herd of breeder pigs. Five pigs that died
      suddenly with diarrhea (SDD pigs) and 6 pigs that died suddenly without signs (SD
      pigs) were examined. The average age of the pigs was about 28 days. Twelve pigs
      of age 10 to 14 days old showing diarrhea (D pigs) were also examined. Eleven of
      them recovered. Large numbers of Escherichia coli were detected in all organs of
      every SDD and SD pig and in feces of D pigs. All of the isolates were identified
      as enterotoxigenic E. coli (ETEC) by the polymerase chain reaction (PCR). Porcine
      reproductive and respiratory syndrome (PRRS) virus cDNA was also detected from
      the lung of every SD and SDD pig by the RT-PCR. High and low titers of antibodies
      to PRRS virus were found in 10-day-old and 1-month-old pigs, respectively. In an
      experiment, 3 ETEC were isolated from 9 healthy weaning pigs during the quiescent
      stage in the herd. These data showed that growth of the ETEC was not active in
      healthy weaning pigs; however, following infection with PRRS virus ETEC infection
      became systemic and caused peracute death in the weaning pigs. It suggested also
      that infection with PRRS virus in 10-day-old pigs were protected by the colostral
      antibodies, and fatal infection by ETEC did not occur as a result.

PMID- 9637288
TI  - Identification of B cell epitopes of a 30 kDa Babesia equi merozoite surface
      protein.
AB  - A 30 kDa immunodominant surface antigen (p30) of Babesia equi has been used as a
      diagnostic antigen. The B cell epitopes on this molecule recognized by horse sera
      and monoclonal antibody (MAb) against p30, 36/133.97, were determined. A
      synthetic peptide of p30 with amino acid sequence of 123FYQEVLFKGFEAV135
      exhibited strong positive reaction with the infected horse sera. In contrast, MAb
      36/133.97 recognized different region of p30, as peptide synthesized with amino
      acid sequence of 27ASGAVVDFQLESI39 reacted strongly. In competitive inhibition
      ELISA, the binding of MAb 36/133.97 to recombinant p30 was inhibited by horse
      antibodies, although they did not recognize same or an overlapping epitope. The
      data on B cell epitopes in this study may be important in improving
      serodiagnostic methods of B. equi infection.

PMID- 9637289
TI  - Bovine viral diarrhea virus replication in bovine follicular epithelial cells
      derived from persistently infected heifers.
AB  - Bovine follicle fluid and oocytes surrounded by follicular epithelial (FE) cells
      were collected from ovaries of two heifers persistently infected with bovine
      viral diarrhea virus (BVDV). BVDV was present in the follicle fluid at a higher
      titer than in serum. The oocytes were matured in vitro under culture conditions
      of 39 degrees C in humidified air containing 5% CO2. In vitro fertilization was
      performed after 24 hr in culture (the day of insemination was defined as day 1),
      and culture was continued through day 10. BVDV was present in the culture medium
      at titers of 10(2.25) to 10(3.25) TC(I)D50/0.1 ml. The virus was also detected in
      FE cells collected on day 10. Viral antigen was demonstrated in the cytoplasm of
      FE cells by the indirect immunofluorescence technique. However, no BVDV was
      detected in the embryos on day 10. These findings suggested that the oocytes or
      embryos were unlikely to be infected with BVDV, but that the FE cells were
      infected with BVDV and supported virus replication in cattle persistently
      infected with BVDV.

PMID- 9637290
TI  - Adhesive and bone resorptive activities of isolated osteoclasts from hen
      medullary bone.
AB  - In the present study, osteoclasts were isolated from hen medullary bones at the
      formative and resorptive phases. The cells were cultured on glass culture dishes
      and bone slices. After culturing, the adhesion activity of the isolated
      osteoclasts with the substrates was estimated with a light microscope, and the
      surfaces of the bone slices were observed with a scanning electron microscope.
      The results showed that the adhesion activity of tartrate-resistant acid
      phosphatase (TRAP)-positive osteoclasts is higher at the bone resorptive phase
      than at the bone formative phase, and this tendency in isolated osteoclasts was
      observed more frequently on the bone slices than on the glass culture dishes.
      Furthermore, scanning electron microscopy showed that the isolated osteoclasts in
      the bone resorptive phase adhered to the bone surface with developed-cytoplasmic
      projections and formed broad pits where collagen fibrils were exposed. On the
      other hand, isolated osteoclasts in the bone formative phase adhered to the bone
      slice with board-shaped cytoplasmic projections and did not form any pits. These
      results suggest that isolated osteoclasts in the bone resorptive phase have a
      high level of adhesion activity and actively resorb the bone, whereas isolated
      osteoclasts in the bone formative phase have a low level of adhesion activity and
      cease bone resorption. The procedure reported here is useful for studying the
      bone-resorptive mechanism of authentic osteoclasts.

PMID- 9637291
TI  - Segregation of bovine viral diarrhea virus isolated in Japan into genotypes.
AB  - It was suggested that 3 strains of bovine viral diarrhea virus (BVDV) isolated
      from persistently infected calves in Tochigi prefecture in Japan belonged to BVDV
      type II. It was recognized lack of PstI site on the 5'-untranslated region of
      genome of them as well as BVDV type II reported previously. Inoculated with the 3
      strains, the calves showed the mild decrease of platelet counts which was
      specific clinical sign of BVDV type II. We should report that the 3 strains were
      the first BVDV type II isolated in Japan. Neutralizing antibody titers of the
      antisera against the 3 strains using laboratory strains as neutralizing virus
      were lower than those of them using homologous strains. Therefore, it was
      indicated that the difference between BVDV type I and BVDV type II in the
      antigenicity.

PMID- 9637292
TI  - Survey of Cryptosporidium oocysts from adult cattle in a slaughter house.
AB  - Cryptosporidian oocysts were surveyed in rectal stools of adult cattle which were
      carried into slaughterhouse from April 1995 to July 1996. We morphologically and
      histologically investigated oocysts, and experimentally infected the isolated
      oocysts to mice and rats. Cryptosporidian oocysts were detected from 24 of 512
      cattle (4.7%). They were spherical or ovoid, and the size was 7.0-7.9 x 5.3-6.1
      microm. Mice and rats inoculated orally with 10(5)-10(7) oocysts became infected
      and discharged oocysts in the feces for a period of more than two months.
      Developing parasites were detected from the stomach of mice, and not detected
      from the other digestive tract. From these findings, present isolates from cattle
      were identified as Cryptosporidium muris.

PMID- 9637293
TI  - Field isolates of transmissible gastroenteritis virus differ at the molecular
      level from the Miller and Purdue virulent and attenuated strains and from porcine
      respiratory coronaviruses.
AB  - The diversity in selected regions of the transmissible gastroenteritis virus
      (TGEV) and porcine respiratory coronavirus (PRCV) genomes was analyzed among
      known TGEV and PRCV strains and field isolates. The N-terminal half of the spike
      (S) glycoprotein gene and open reading frames (ORF) 3, 3-1 and 4 were amplified
      by reverse transcriptase reaction and polymerase chain reaction (RT/PCR), and
      analyzed using restriction fragment length polymorphism (RFLP) patterns of the
      amplified DNA. Reference TGEV strains (Miller and Purdue) and a PRCV strain (ISU
      1), and TGEV and PRCV field isolates were analyzed. Based on the size of the ORF
      3, 3-1 and 4 RT/PCR products, TGEV and PRCV strains could be quickly and easily
      differentiated into three groups designated TGEV Miller, Purdue types and PRCV.
      By RFLP analysis of the N-terminal region of the S glycoprotein gene and ORFs 3,
      3-1 and 4, TGEV and PRCV strains were differentiated into five groups using the
      restriction enzyme Sau3AI. Sequence analysis of a PCR product in the ORFs 3, 3-1
      and 4 from virulent and attenuated Miller strains demonstrated additional
      differences in that region which have been correlated with a change in virulence
      of TGEV isolates.

PMID- 9637294
TI  - Epitope mapping of bovine leukemia virus transactivator protein Tax.
AB  - The immunogenicity of the bovine leukemia virus (BLV) transactivator protein
      (tax) was studied by mapping its B-cell and T-cell epitopes. Peptides (18 to 20
      mer) overlapping by 10 amino acids, spanning whole amino acid sequence of BLVtax
      were synthesized. Recombinant BLVtax protein was used to immunize two different
      strains of mice, C57BL/6 and BALB/c. B-cell and T-cell epitopes of recombinant
      BLVtax protein was determined by screening all the 30 synthetic peptides, against
      immune serum in ELISA for antibody reactivity, and against immune spleen cells in
      lymphocyte proliferation assay for T-cell stimulation. Peptides with amino acids
      at position 111-130 and 131-150 were T-cell epitopes for C57BL/6 and BALB/c mice
      immune cells, respectively. B-cell epitope was mapped to amino acid sequence at
      261-280 in both strains of mice. These results imply that BLVtax protein contains
      some of BLV- immunodominant epitopes and this information may be applied for
      designing an effective peptide vaccine capable of inducing neutralizing
      antibodies as well as cellular immunity.

PMID- 9637295
TI  - Changes in semen quality and in vitro sperm capacitation during various
      frequencies of semen collection in dogs with both asthenozoospermia and
      teratozoospermia.
AB  - Eight male dogs with both asthenozoospermia and teratozoospermia were used in
      this study. In experiment 1, semen was collected 10 times at intervals of 48 hr,
      24 hr and 12 hr in 4 of the 8 dogs, and the semen quality was evaluated. In
      experiment 2, semen was collected 5 times at 24-hr intervals in the other 4 dogs.
      The spermatozoa collected on day 1 and day 5 were incubated for 4-6 hr in Canine
      Capacitation Medium, and the percentages of hyperactivated sperm (%HA), acrosome
      reacted sperm (%AR), and the zona pellucida-binding sperm count (ZP sperm count)
      were assessed. The results of experiment 1 showed that the percentage of motile
      sperm increased and the percentage of abnormal sperm decreased markedly as the
      intervals between semen collections became shorter. When semen was collected at
      12-hr intervals, the percentage of motile sperm increased from about 65%, the
      value before frequent collection was started, to about 80%, and the percentage of
      sperm with abnormal tails decreased from 30% to 15%. In experiment 2, the
      percentages of HA and AR, and the ZP sperm count in specimens collected on day 5
      were higher than those in specimens collected on day 1, and the differences in %
      HA and in ZP sperm count were significant (P<0.05). The results demonstrated that
      sperm motility, abnormality, and potential fertility in dogs with
      asthenozoospermia and teratozoospermia can be temporarily improved by frequent
      semen collection.

PMID- 9637296
TI  - The location of a specific epitope in the SU proteins of palysis-inducing PVC
      murine leukemia viruses.
AB  - The location of a specific epitope in the SU proteins (gp70s) of PVC (PVC-111,
      PVC-211, PVC-321 and PVC-441) murine leukemia viruses (MuLVs) among various MuLVs
      was determined with chimeric viruses between PVC-211 and F-MuLV and a rat
      monoclonal antibody to the gp70 of PVC-321. The epitope resided in the N-terminal
      region from amino acid position 1 to 67 of SU protein and did not correlate to
      the tropism against brain capillary endothelial cells of the F344 rat or Chinese
      hamster ovary cells.

PMID- 9637297
TI  - Urinary bladder rhabdomyosarcoma (sarcoma botryoides) in a young Newfoundland
      dog.
AB  - A 13-month-old female Newfoundland dog suffered from urinary bladder tumor.
      Histologically the tumor consisted of round or fusiform cells, occasionally
      having eosinophilic cytoplasms. Apparent mature rhabdomyoblasts possessing
      elongated eosinophilic cytoplasm and cross striations were infrequently observed.
      The tumor cells exhibited immuno-positive for anti-myoglobin, desmin and vimentin
      antibodies. Ultrastructurally, tumor cells have abundant myofibrils in their
      cytoplasm and Z bands were also detected. The present tumor was diagnosed as a
      urinary bladder rhabdomyosarcoma in a Newfoundland dog, which has not been
      frequently reported in dogs.

PMID- 9637298
TI  - Histological variations of canine deciduoma induced in non pregnant horn at
      different stages of unilateral pregnancy.
AB  - Histological variations of canine deciduoma which was induced in the non pregnant
      horn at several stages of unilateral pregnancy were examined. In the first half
      of the unilateral pregnancy, deciduoma was characterized by the cystic glandular
      hyperplasia corresponding to each of the stages in normal early placentation. In
      the second half, deciduoma could not be induced and few histological reactions
      were recognized. The endometrium looked normal for late diestrus with no growth
      of the uterine glands. These differences might reflect the latent strength of the
      uterine glands to proliferate and dilate in the stimulated periods.

PMID- 9637299
TI  - Encephalitis in mice inoculated intranasally with an influenza virus strain
      originated from a water bird.
AB  - Five-week-old ddY mice were inoculated intranasally with a low virulent (4e) or
      highly virulent (24a5b) avian influenza virus strain originated from a water
      bird. None of mice in the 4e group showed clinical signs and brain lesions. Of
      the 24a5b group, two mice died and one mouse was killed at a moribund state at
      day 7 post-inoculation (PI). Four mice of the 24a5b group necropsied at day 5 or
      7 PI had mild to severe encephalitis in the brain stem and the cerebellar white
      matter. Influenza virus antigen was detected in neurons, glial cells and vascular
      endothelium in the lesions. The distribution of the lesions seems to indicate the
      transneuronal invasion of the virus via cranial nerve fibers into the brain.

PMID- 9637300
TI  - Immunohistochemical study of protein kinase C in the testes of cattle and pigs.
AB  - We investigated the expression of novel protein kinase C (PKC) delta and theta in
      the testes of pigs and cattle using Western blot and immunohistochemical
      analysis. PKC delta and theta are recognized in the testes of pigs and cattle by
      Western blot analysis. We found in immunohistochemical study that PCK delta was
      localized in the spermatids of seminiferous tubules, but not in the interstitial
      cells, while PKC theta was recognized only in the interstitial cells of the
      testes of in both species. These findings suggest that PKC delta and theta play
      an important role in the development of spermatozoa and the regulation of
      androgen in the testicular interstitial cells (probably Leydig cells),
      respectively.

PMID- 9637301
TI  - Application of hepatic tolerance tests to the functional reserve assessment in
      rat models of fatty liver.
AB  - The present study was designed to define whether maximal removal rate of
      indocyanine green (ICG Rmax), plasma cyclic 3',5'-adenosine monophosphate (cAMP)
      response to exogenous glucagon (peak to basal ratio of cAMP level: P/B cAMP) and
      plasma half-life of galactose (t1/2 galactose) can measure the hepatic functional
      reserve of fatty liver prepared in rats fed choline-deficient (9 weeks), 2%
      cholesterol (2 weeks) or 0.25% DL-ethionine (2 weeks) diet. Although changes in
      cholesterol and phospholipid values in serum during feeding periods differed
      among the models, histopathologic examinations in the liver of almost all animals
      revealed intermediate to severe fatty liver with or without fibrosis at each
      termination. ICG Rmax and P/B cAMP were significantly decreased in rats fed
      choline-deficient or DL-ethionine diet, implying reductions in hepatic functional
      mass and disturbances in hepatic cAMP production. Meanwhile, t1/2 galactose
      showed no change in any of the models, suggesting that glucose metabolisms in the
      models used may be preserved. These findings demonstrate that ICG Rmax and P/B
      cAMP can apply to measurement of hepatic surviving reserve of fatty liver with
      fibrosis.

PMID- 9637302
TI  - Coproantigen detection in a survey of Echinococcus multilocularis infection among
      red foxes, Vulpes vulpes schrencki, in Hokkaido, Japan.
AB  - Detection of Echinococcus coproantigen using sandwich enzyme-linked immunosorbent
      assay (sELISA) was performed on fecal samples of red foxes in Hokkaido, Japan.
      Fecal samples were collected around fox dens in 1990 and 1992. The antibodies
      used for sELISA recognize heat-resistant antigens, thus all fecal samples were
      heated to render it safe for handling before examination. Detection of taeniid
      egg in fox feces collected was considered as an indication of E. multilocularis
      infection. In fecal samples collected in 1990 and 1992, coproantigen positive
      results out of taeniid-egg positive cases were 38/40 (95.0%) and 95/97 (97.9%),
      respectively. In addition, coproantigen was detected regardless of fecal
      condition when collected from the field, suggesting that the antigens detected by
      this method are quite stable. These results suggest that detection of
      coproantigen is useful for field surveys of foxes naturally infected with E.
      multilocularis.

PMID- 9637303
TI  - Relationship between plasma testosterone concentrations and age, breeding season
      and harem size in Misaki feral horses.
AB  - Jugular vein blood samples were collected from 23 young and sexual mature feral
      stallions to examine the relationship between plasma testosterone concentration
      and age, breeding season or harem size. Testosterone concentration increased with
      the age of the stallions until they formed their own harems, at about 4 to 6
      years old. Seasonal variations in testosterone concentrations were observed, and
      found to be significantly higher (P<0.001) throughout the breeding season than
      non-breeding season, from 3 years of age. Testosterone levels were correlated
      with harem size for individual stallions. It can be inferred from these results
      that there is a relationship between plasma testosterone concentration and age,
      breeding season and harem size.

PMID- 9637304
TI  - The contrecoup injury in a cat case of traffic accident: MRI findings.
AB  - The clinical application of MRI of a cat case of traffic accident was examined.
      On admission, the animal was unconscious and remained so for 2 days. Radiographs
      disclosed a fracture in the parietal bone. From the temporary unconscious status
      and the fracture, cerebral damage was suspected and an MRI examination was
      performed. The contrecoup injury in the cat case of traffic accident which could
      not be diagnosed by radiography was diagnosed by MRI examination.

PMID- 9637305
TI  - Cloning and mapping of the mouse Gpx2 gene encoding gastrointestinal glutathione
      peroxidase.
AB  - Gastrointestinal glutathione peroxidase (GSHPx-GI) is an enzyme expressed in
      intestinal epithelial cells and may reduce hydroperoxides generated from the
      ingested diet. We isolated a genomic clone containing the mouse Gpx2 gene
      encoding 190 amino acids of GSHPx-GI. This gene is composed of two exons and an
      intron. The nucleotide sequence of the coding region was 89.9% identical with
      that of the human GPX2 gene. A TGA opal codon predicted to encode a
      selenocysteine was identified at codon 40. A genomic clone containing a
      pseudogene for the Gpx2 gene was also isolated. The nucleotide sequence of the
      pseudogene was 98.3% identical with that of the mouse Gpx2 gene and showed
      characteristics of a processed pseudogene. Linkage analysis using backcross mouse
      progeny indicated the mouse Cpx2 gene and its pseudogene to be located on mouse
      chromosomes 12 and 7, respectively.

PMID- 9637306
TI  - Construction of recombinant vaccinia virus expressing Rinderpest Virus
      nucleocapsid protein and its immunogenicity in mice.
AB  - Recombinant vaccinia virus (rVV) was constructed by inserting Rinderpest Virus
      (RPV) nucleocapsid (N) protein gene. The rVV expressed RPV-N protein in the rVV
      infected cells. The rVV was shown to produce RPV-N-specific antibody in mice.

PMID- 9637307
TI  - Effect of thromboxane synthetase inhibitor on feline infectious peritonitis in
      cats.
AB  - Two cats with abdominal effusion and anorexia were diagnosed as feline infectious
      peritonitis (FIP). We tried to evaluate the effect of thromboxane (Tx) synthetase
      inhibitor, ozagrel hydrochloride, on the progression of symptoms and
      clinicopathologic data characteristic to FIP. After administration of Tx
      synthetase inhibitor, improvement of appetite and activity, decreases of
      peritoneal effusion, reduction of leukocyte number to normal level, and
      improvement of hyper gamma-globulinemia were found in 2 cats with FIP. These
      findings suggest that the vasculitis in FIP can be successfully treated with Tx
      synthetase inhibitor which inhibits platelet aggregation.

PMID- 9637309
TI  - Law, ethics and risk in nursing practice.

PMID- 9637308
TI  - Comparative pharmacokinetic profiles of two norfloxacin formulations after oral
      administration in rabbits.
AB  - The pharmacokinetics and tissue distribution of two norfloxacin (NFLX)
      formulations, norfloxacin-glycine acetate (NFLXGA) and norfloxacin nicotinate
      (NFLXN), were compared after single oral administration with a dose of 5 mg
      equivalent NFLX base/kg of body weight in twenty rabbits. The pharmacokinetic
      characteristics of all formulations were fitted by a two-compartment open model.
      The elimination half-life (T1/2beta) of NFLX (3.37+/-1.37 hr) was not significant
      as compared with those of NFLXN (3.61+/-0.65 hr) and NFLXGA (3.93+/-1.54 hr). The
      absolute bioavailability (F) of NFLX, NFLXN and NFLXGA was calculated as 29%, 45%
      and 40%. In addition, tissue distribution of NFLXN and NFLXGA did not show any
      differences of NFLX concentrations in liver, kidney, serum and muscle. From the
      present results, it could be suggested that NFLXN and NFLXGA are considered to be
      bioequivalent when they use oral medication for rabbits.

PMID- 9637310
TI  - WHO tackles health risks in European prisons.

PMID- 9637311
TI  - Role of nurses in the community care of schizophrenia.

PMID- 9637312
TI  - Teenage risk from painkillers.

PMID- 9637313
TI  - Towards a partnership in care: nurses' and doctors' interpretation of extremity
      trauma radiology.
AB  - Receiver operating characteristic (ROC) is a method of assessing the sensitivity
      and specificity of a classification at a variety of thresholds. It allows a
      quantitative comparison of several classifiers. It was used in this study to
      compare doctors and nurses with respect to their ability to diagnose X-rays. X
      ray interpretations were measured using a confidence rating scale, on 50
      radiographs from a generated library of extremity X-rays following trauma. The
      catalogue of radiographs were selected from real cases of extremity trauma which
      were considered representative of typical accident and emergency case scenarios.
      The interpretations of doctors and nurse practitioners were compared with the
      gold standard of the consultant radiologist. No significant differences were seen
      between the two groups. This study is based on work done for a master's thesis by
      one of the authors (Overton) supervised by the other author.

PMID- 9637314
TI  - Handling and control of peripheral intravenous lines.
AB  - The purpose of the study was to describe nurses' routines in connection with the
      planning, care and handling, and documentation of a peripheral intravenous
      cannula (PIV) and also to examine factors that control how nurses act. Nurses and
      physicians in three English hospitals were interviewed. The results showed a
      difference between nurses' and physicians' opinions about PIV routines, except in
      few cases. The PIV was inserted by the physicians while the nurses took care of
      and documented its care and handling. In many cases the insertion of the PIV was
      also documented by the nurses. Although small PIVs and short insertion time had
      previously been recommended, many physicians preferred large cannulae and an
      insertion time of between 3 and 7 days. All nurses and six physicians had the
      opinion that the cannula should be changed more often, but this did not happen.
      Some physicians maintained that the nurses' care and handling varied. On the
      other hand some criticism had been expressed by the nurses about unclear
      directives from the physicians. English participants were aware that
      unsatisfactory routines existed and that the policy had not always been followed.

PMID- 9637315
TI  - 'Out of the sighs'--an existential-phenomenological method of clinical
      supervision: the contribution to palliative care.
AB  - This paper describes a method of clinical supervision that engages a Macmillan
      home care nurse in an existential-phenomenological exchange. A synthesis of
      Egan's method of problem management and phenomenological interviewing, is offered
      as an approach to clinical supervision considered appropriate for palliative care
      nursing. Through a case study approach the author affords glimpses into the life
      world of palliative care nursing. It is suggested that conflicts experienced in
      the field both manifest themselves in the supervisory encounter and parallel the
      nurse's and supervisor's own existential struggles. The discussion as such throws
      light on what is, frequently, the heart rending nature of palliative care nurses'
      chosen area of work and illuminates the mutual profundity of the experience of
      palliative care.

PMID- 9637316
TI  - Patients' and nurses' perceptions of the quality of nursing care in Kuwait.
AB  - Using an exploratory research method and a purposive sample of 259 subjects (109
      of whom were nurses and 148 patients), data were collected using an instrument
      consisting of the elements of the nursing process. Four hypotheses were tested,
      using the analysis of covariance and the t-test The result of hypothesis I showed
      that there was no statistically significant difference in the perception of the
      quality of nursing care between the patients in the medical and surgical units of
      the five study hospitals. Hypothesis 2 indicated that there was no significant
      difference between nurses in the medical-surgical units in the areas of
      assessment, planning and implementation. However, a significant difference was
      found for accountability and responsibility. Further analysis using a t-test
      showed a significant difference between nurses in the medical and surgical units
      in the areas of accountability and responsibility. The data for hypothesis 3 and
      4 yielded no significant difference in the perceptions of quality care by nurses
      according to work experience and by patients in all hospitals regardless of the
      patients' age and sex.

PMID- 9637317
TI  - A review of the outcome of stoma surgery on spinal cord injured patients.
AB  - A study was conducted to determine the short-term and long-term outcome of stoma
      formation on spinal cord injured (SCI) patients. Twenty-seven medical records of
      SCI patients with colostomy, ileostomy or urostomy were reviewed. Eighteen SCI
      patients were then interviewed or completed a comprehensive questionnaire to
      determine the physical and psychological effects of the surgery and to assess
      changes in lifestyle due to the formation of the stoma. It was found that bowel
      and bladder management was greatly improved in most cases, resulting in improved
      quality of life for these patients. Other positive psychological effects were
      noted and the question of a colostomy being offered earlier in the rehabilitation
      of the SCI patient was raised.

PMID- 9637318
TI  - Nurse caring behaviours.
AB  - The purpose of this research paper is to examine caring behaviours and how they
      relate to nurses practice from the psychiatric and general nurses' views. Whether
      this caring is influenced by the nurses' age, gender or qualification is also
      examined. The convenience sample used were nurses (n = 118) of all grades and
      experience in a general hospital and in a psychiatric hospital. The Care-Q
      instrument was used. The response rate was 66%. Statistical analysis included
      rankings of sub-scale and individual items and the chi-square test of
      association. The results show that nurses ranked physically based caring
      behaviours higher than affective behaviours. They emphasized monitoring and
      comforting behaviours but paid less attention to anticipatory behaviours. Gender
      appeared to have the greatest influence on what caring behaviours were valued.
      Male nurses were less likely than female nurses to be accessible, forming
      trusting relationships or performing comforting behaviours. The results challenge
      both nurses and nurse educators to examine caring behaviours in nursing practice.

PMID- 9637319
TI  - Case management: a review of the definitions and practices.
AB  - Case management has been suggested as an innovative strategy which facilitates
      the linking of quality and cost-effective care. However, there is little
      consensus about what is actually being introduced under the name of case
      management. It is suggested that this absence of a clear understanding of case
      management has been an obstacle in moving forward case management practice and
      research. This paper presents a critical review of the confusion surrounding case
      management with an attempt to unravel issues relevant to the implementation of
      case management into community nursing practice in Hong Kong. It is concluded
      that there is a need for different definitions of case management as a result of
      the differences in the cultural and health care context in which it is being
      practised. Also, if case management programmes are to be advanced, there needs to
      be more co-ordinated effort in researching not only the expected outcomes but
      also the structures and processes of these programmes so that findings of similar
      case management programmes can be compared for ways of future improvement.

PMID- 9637320
TI  - Privacy in hospital.
AB  - Privacy during hospitalization can be jeopardized as caring situations are often
      intimate. The aims of the current study were to explore patients' and nurses'
      attitudes towards privacy and to study whether nurses' perceptions of patients'
      privacy needs corresponded with the patients' own reported needs. Two
      questionnaires were used for the data collection, which included 120 consecutive
      patients and 42 nurses responsible for the participating patients' individual
      care. The main findings indicated that patients and nurses agree in the ratings
      of the major components of privacy in general, but privacy in hospital was
      estimated more highly by the nurses than by the patients themselves. Being
      allowed to talk to the physician in private was given the highest preference.
      Patients in long-term care had higher privacy preferences than those in acute
      care. An explanatory approach is needed to study the need for privacy in
      different caring situations and how privacy needs could be recognized and met by
      nurses.

PMID- 9637321
TI  - The philosophical and sociological context of mental health care legislation.
AB  - This paper explores mental health legislation from a philosophical and
      sociological perspective. It is argued that mental health law exists primarily as
      a coercive social control instrument and that the maintenance of a separate
      legislative framework for the mentally ill is based upon dubious legal and
      philosophical grounds. The need for changes in mental health law has been
      accelerated by the move in Britain toward care in the community. One of the most
      important issues at the centre of the debate revolves around the concept of
      'dangerousness' and mental disorder. The research into the extent to which the
      risk of violence can be predicted appears problematic from a reform perspective.
      Prediction is considered to be the overriding problem that leads to a violation
      of patients' civil rights, especially in relation to black and ethnic minority
      groups. Equity in law is necessary for the protection of patient's rights and
      particularly for the protection of those people who enter mental health care
      systems concerned with issues of control at the expense of care.

PMID- 9637322
TI  - Perceived social support and community adaptation in schizophrenia.
AB  - Prompted by the continuing transition to community care, mental health nurses are
      considering the role of social support in community adaptation. This article
      demonstrates the importance of distinguishing between kinds of social support and
      presents findings from the first round data of a longitudinal study of community
      adaptation in 156 people with schizophrenia conducted in Brisbane, Australia. All
      clients were interviewed using the relevant subscales of the Diagnostic Interview
      Schedule to confirm a primary diagnosis of schizophrenia. The study set out to
      investigate the relationship between community adaptation and social support.
      Community adaptation was measured with the Brief Psychiatric Rating Scale (BPRS),
      the Life Skills Profile (LSP) and measures of dissatisfaction with life and
      problems in daily living developed by the authors. Social support was measured
      with the Arizona Social Support Interview Schedule (ASSIS). The BPRS and ASSIS
      were incorporated into a client interview conducted by trained interviewers. The
      LSP was completed on each client by an informal carer (parent, relative or
      friend) or a professional carer (case manager or other health professional)
      nominated by the client. Hierarchical regression analysis was used to examine the
      relationship between community adaptation and four sets of social support
      variables. Given the order in which variables were entered in regression
      equations, a set of perceived social support variables was found to account for
      the largest unique variance of four measures of community adaptation in 96 people
      with schizophrenia for whom complete data are available from the first round of
      the three-wave longitudinal study. A set of the subjective experiences of the
      clients accounted for the largest unique variance in measures of symptomatology,
      life skills, dissatisfaction with life, and problems in daily living. Sets of
      community support, household support and functional variables accounted for less
      variance. Implications for mental health nursing practice are considered.

PMID- 9637323
TI  - Psychosocial changes following retirement.
AB  - This study was designed to: (a) identify the perceptions of retirees about
      changes in their life patterns during retirement; (b) investigate the kinds of
      adjustment problems occurring in retirement as a basis for developing prevention
      oriented pre-retirement programs; and (c) identify extant factors which could
      demonstrate underlying themes relating to retirement adjustment. A 72-item,
      multiple response questionnaire was used to gather demographic data, information
      on use of time, pre-retirement planning, health problems, changing life patterns,
      and adjustment to retirement. It is the latter which is reported in these
      findings. The population included 1565 retirees from a designated company living
      in the south-eastern United States of America, with a response of 764 subjects
      (48.82%). Findings suggest the respondents were generally healthy and well
      adjusted; however, numerous adjustment problem areas were identified within the
      six life patterns. Additional factor analysis (principal components) demonstrated
      four factors of particular importance: satisfaction with retirement, retirement
      concerns, spousal relationships, and pre-retirement preparation outcomes.

PMID- 9637324
TI  - Mentally restorative experiences supporting rehabilitation of high functioning
      elders recovering from hip surgery.
AB  - Because mentally restorative experiences are pivotal in the context of
      rehabilitation and recovery, a prospective descriptive study was designed to
      learn more about the opportunities for, locations, and actions taken by, a group
      of elderly people (n = 8) over the age of 60 (average age = 82.5) that resulted
      in agreeable or pleasurable states of mind and perceived improvement in their
      ability to pay attention. Both structured and unstructured interviews were used
      to describe elderly patients' past and current patterns of and preferences for
      mentally restorative experiences. Data collection procedures were utilized during
      complete lengths of stay (range = 14-62 days) in sub-acute care. Results
      demonstrate that the actions elderly people take to create opportunities for
      mentally restorative experiences are related to past patterns of restorative
      activities, opportunities made available by the facility, special circumstances
      of their care, environmental limitations in the immediate care environment, and
      the degree to which external factors (such as family visits) are readily
      available. Implications for designing and managing the care environment are
      discussed.

PMID- 9637325
TI  - Labour ward midwives' perceptions of stress.
AB  - This exploratory study set out to examine labour ward midwives' perceptions of
      stress. It utilized a combination of two self-report questionnaires, one devised
      by McGrath et al. and the GHQ12. Additional qualitative data were collected by
      asking midwives to produce narratives about recent stressful events. A
      convenience sample of the 43 midwives formed the study population and a response
      rate of 77% was achieved. Quantitative data were analysed using descriptive
      statistics and qualitative narratives were explored for content analysis.
      Midwives in this study demonstrated their awareness of stress in their working
      and personal lives and many took active steps to redress the negative effects
      with exercise, hobbies and talking with colleagues. However, the study revealed
      that 78% of the midwives indicated that having insufficient time to perform their
      duties was very stressful, paralleled by their perceived inability to influence
      work-based decisions. The study revealed that both medical and midwifery
      colleagues frustrated their endeavours to change an unsatisfactory condition. The
      GHQ12 revealed 30% of the midwives had scores above the threshold level of 2
      indicating psychiatric morbidity and this is of major concern. The narratives
      revealed that lack of communication between the professionals about decision
      making was a major source of stress and as a result of this study efforts to
      improve multidisciplinary communication through the development of journal clubs
      and planned social activities is under consideration by the unit. Overall, the
      findings from this study highlight stress as a potential, occupational health
      problem in the working lives of some labour ward midwives.

PMID- 9637326
TI  - Infertility and early parent-infant interactions.
AB  - Approximately 50% of infertile couples will become parents through pregnancy or
      adoption, but they experience major difficulties while working towards this goal.
      Infertility treatments are associated with physical pain and psychological
      distress, and adoption procedures are prolonged and emotionally stressful. The
      extent to which these stressors alter the parenting of these couples is not
      known. The purpose of this study, therefore, was to examine the early parent
      infant interactions in infertile couples who become parents through pregnancy or
      adoption. Two groups of infertile couples (30 who achieved pregnancy and 21 who
      adopted) and a group of 19 couples without fertility problems were observed
      interacting with their infants twice, 7 to 21 days after the infant's arrival and
      a week later, at a time when both parents were at home. Their babies were between
      9 days and 5 months of age. Behaviours of the mother, father and infant were
      recorded every 10 seconds, beginning when the baby was picked up and ending when
      the baby was put down asleep or 1 1/2 hours had passed. Repeated measures ANOVAs
      were used to compare the three groups over the observations. There were no
      differences between fertile and infertile biological parents. Adopted infants
      showed more alertness, less sleeping, more smiles, and more looking than
      biological infants. Adoptive mothers spent less time as the sole interactor.
      Adoptive parents spent more time in playing with their infants and held and
      touched them less than did biological parents. Infertility, therefore, does not
      appear to affect early parenting. In general, the amounts of behaviours exhibited
      by infertile biological parents were very close to those of fertile parents.
      Differences in the behaviours of adoptive as compared to biological parents can
      best be explained as responses to the behaviours of their older infants, rather
      than as evidence of different parenting styles.

PMID- 9637327
TI  - The role of cognitive-behavioural therapy in the management of pain in patients
      with sickle cell disease.
AB  - Painful crisis is the most common manifestation of sickle cell disease and
      accounts for the second greatest number of admissions with an average length of
      stay of 7 days in central London. Despite this frequency of admissions, the
      management of pain is fraught with problems. This is not surprising since the
      psychological challenges presented by sickle cell disease are manifold, resulting
      in significant psychological distress for some individuals. This paper considers
      the literature on the psychosocial impact of sickle cell disease, and the
      American research evidence which suggests that pain management strategies that
      incorporate a psychological intervention can significantly reduce psychological
      distress as well as hospital admissions. Britain has been slow to incorporate
      psychology in the pain management strategies, and we have embarked on research to
      fill this gap. Although this research constitutes work in progress, an argument
      is put forward for utilizing the cognitive-behavioural perspective in the
      management of pain in sickle cell disease and we conclude by giving a brief
      summary of pilot work which is both the foundation and justification for the
      current ongoing research.

PMID- 9637328
TI  - Towards a politics of trust.
AB  - This paper draws upon sociological theory to demonstrate that the manufacture and
      deployment of trust is an integral part of the function of complex systems such
      as health care. The discussion begins by identifying the error within the nursing
      literature which arises from a rather technical conceptualization of trust. This
      tends to limit the dimensions to trust which is established, and fails to
      recognize that trust may be subject to competition and conflict. The paper
      continues by drawing upon the work of two theorists, Niklas Luhmann and Susan P.
      Shapiro, to demonstrate how trust functions within systems such as health care
      and the mechanisms through which it is controlled. The title of this paper,
      'Towards a politics of trust', identifies that this is merely the first stage in
      the analysis. Further stages are necessary which analyse the ways in which power
      is exercised in the conflict for control within discrete elements of the system.

PMID- 9637329
TI  - A framework to identify learning needs for continuing nurse education using
      information technology.
AB  - This paper concerns one of the main problems facing continuing nurse education,
      that of matching the learning needs of the individual nurse with the needs of the
      care setting. This endeavour is inescapable because of the necessity for giving
      high quality care within financial restraint. Modern information technology, it
      is suggested, can be helpful in fulfilling the task more easily. A theoretical
      framework is introduced as a possible solution for developing a computer program
      which, it is the hope of the author, will be available in the not so far future.

PMID- 9637330
TI  - 'The buck stops here': accepting responsibility for learning and actions after
      graduation from a problem-based learning nursing education curriculum.
AB  - Despite the increased attention that problem-based learning has received as an
      appropriate pedagogical technique for educating adults for professional practice,
      reports that evaluate the process are rare and usually relate to professions
      other than nursing. A study was undertaken in order to discover the graduates'
      own perceptions of a problem-based learning programme and its effectiveness in
      preparing them for the reality of their chosen profession. Twelve practising
      graduate nurses who had completed the programme were interviewed according to the
      ethnographic method. Three categories were identified from the data: 'and all of
      a sudden...', which describes the transition from PBL student to staff nurse;
      'not an unthinking assistant', where the characteristics that the PBL graduates
      believe make them different from traditionally trained nurses are described; and
      'the buck stops here', which describes the sense of personal responsibility that
      the graduates experience in terms of their learning and actions.

PMID- 9637331
TI  - Learning by reflection: the effect on educational outcomes.
AB  - Learning by experience involves being able to reflect on a personal happening and
      through a process of analysis, come to understand it. Such an activity should
      result in 'deep learning' when carried out in a structured way. Higher education
      establishments are keen to develop such learning methods in students, as a
      secondary effect of this form of learning is to create student independence from
      the teacher. This is a much sought after ability as recent government changes
      have meant higher student numbers without a corresponding rise in teacher
      numbers. This threatens the quality of student knowledge unless it is compensated
      for in some way. This study sets out to examine the learning of two student
      groups. The experimental design was that of group comparison using matched pairs
      of students. One group, the experimental group, were exposed to reflective
      teaching methods, whilst the other group (the control group) were exposed to
      conventional teaching methods only. At the end of a set period of time, the
      learning achieved in both groups was estimated using an especially designed test
      paper. The results obtained from both groups were compared and it was found that
      there was no significant difference obtained in the learning between the groups
      (P>5%) Therefore, we concluded that students learnt just as well using reflective
      methods when compared to the conventional methods of learning. However, the
      potential for enhancement of learning was evident and invites further
      investigation. All the students in this study were on the Diploma in Higher
      Education (Nursing) course. The subject area used throughout the study was in the
      biological sciences.

PMID- 9637332
TI  - Planning flexible learning to match the needs of consumers: a national survey.
AB  - The injection of market forces into the National Health Service (NHS) has led to
      nurse education being viewed as a commodity which educational institutions supply
      and NHS employers purchase. Conscious of the costs of paying for courses within
      this new consumer culture, NHS trusts and other health service employers are
      increasingly looking for cost-effective flexible training to educate their
      workforce quickly and efficiently. Parallel to this is the accelerated demand for
      continuing professional development (CPD) brought about by the inception of the
      UKCC's Post-Registration Education and Practice Project (PREPP). Both registered
      and enrolled nurses are finding they need professional updating and skills and
      thus increased access to courses. The increased demand for education and training
      brought about by these changes cannot be met through traditional methods alone,
      requiring educational institutions to re-appraise their methods of delivery and
      introduce more flexible approaches to learning. There is every evidence that this
      is now the case with open learning, distance learning and flexible approaches to
      learning ever growing in popularity as providers of nurse education recognize the
      benefits such approaches offer. The emphasis is on meeting the diverse needs of
      the health care employers and individuals by providing education that is
      flexible, learner-centred and customer focused. This paper presents the findings
      of a national survey to ascertain how providers of flexible education plan
      educational programmes to meet the needs of their customers. Based on data
      collected from 120 educational institutions within the higher education, health
      and social care and private sectors, it highlights: the ways in which flexible
      learning programmes and courses are delivered; what aspects of flexibility are
      considered important when designing programmes to meet the needs of prospective
      customers; and what approaches are used to assess demand for flexible education.
      The study stresses the need for providers of flexible education to take into
      account the dual perspectives of those who have a stake in the flexibility of
      nurse education; NHS employers as funders of students and individual healthcare
      professionals themselves.

PMID- 9637333
TI  - The role of reflection in single and double loop learning.
AB  - A recent review of the literature on reflective practice in nursing indicates
      that approaches to its promotion in the United Kingdom and Australia appear to
      differ. In the United Kingdom, these approaches promote single-loop learning
      whereas in Australia the approaches adopted attempt to promote double-loop
      learning. In this paper single and double-loop learning will be defined and the
      limitations of single-loop learning in nurse education will be discussed. In
      addition, definitions of reflective practice, the purposes it is claimed to serve
      and a range of frameworks developed to promote its development will be reviewed.
      Inconsistencies between espoused purposes and suggested frameworks will be
      discussed. The paper will also include a description of recent initiatives
      implemented in Western Sydney, Australia, to foster nurses' double-loop learning.

PMID- 9637334
TI  - Reflection and patterns of knowing in nursing.
AB  - Over the last decade nursing has progressed from a reliance on empirical theory
      applied to practice to a recognition that experience develops knowledge that can
      guide the actions of practitioners. Reflection is a means of surfacing
      experiential knowledge, and students may begin to use reflection as their
      experience of nursing accumulates. As Carper was a key figure in widening that
      knowledge accepted as knowing in nursing beyond the empirical, it is both
      justified and recommended that her work should be incorporated into reflective
      practice. Johns has integrated Carper's work in his model of guided reflection
      and this paper briefly examines this combination. The main focus is on two
      further patterns of knowing: unknowing and sociopolitical knowing. These patterns
      are examined and the contribution they could make to reflective practice is
      discussed.

PMID- 9637335
TI  - Using bioscience knowledge in nursing: actions, interactions and reactions.
AB  - This paper draws on empirical data from a study undertaken to explore the
      outcomes of the applied physiology component of a post-registration diploma in
      nursing (DN). Most students completing the DN were utilizing their new bioscience
      knowledge in clinical practice, and reported increased participation in
      interprofessional discussions and team decisions. Respondents found themselves
      better able to monitor and evaluate doctors' decisions and this led to friction
      with some medical colleagues. However, the strongest resistance came from senior
      nurses, very few of whom had completed advanced nursing courses in bioscience and
      who were generally unwilling to allow respondents to develop new roles. General
      managers were also perceived as a major barrier to change. There is little
      evidence of tangible benefits to the nurses themselves: most saw the DN
      qualification as a way of protecting their status as professional nurses in the
      face of managerially driven organizational change, rather than as a route to
      occupational advancement.

PMID- 9637336
TI  - 'A good person does not feel envy': envy in a nursing community.
AB  - The definition of envy is commonly based on psychoanalytical views of
      organizational culture. The purpose of this paper is to describe envy in a
      nursing community. The population study consisted of random sample of 120
      subjects drawn from among the employees of one central hospital in Finland. The
      study material consisted of data collected by questionnaires (response rate 65%).
      The data were processed by various statistical methods. Open-ended questions were
      analysed by inductive content analysis. The results of this study indicated that
      the employee's view of his/her official position in the nursing community,
      his/her relationships with his/her fellow workers and the management as well as
      relationships with other nursing communities are all related to envy. The
      employee's view of his/her official position intensified his/her feelings of
      envy, if he/she had other negative feelings, anxiety, dissatisfaction with
      him/herself, and negative feelings towards fellow workers. The major object of
      envy was fellow workers' salaries. Envy towards other nursing communities was
      generated by alleged differences in the amount of labour, or by the charge
      nurse's greater interest in other sections. Employees coped with envy by hiding
      these feelings and being modest. Women coped with envy by being silent, while men
      denied the value of the object of envy.

PMID- 9637337
TI  - The effects of aftercare on chronic patients and frail elderly patients when
      discharged from hospital: a systematic review.
AB  - The purpose of this systematic review was an assessment of the efficacy of
      aftercare in chronic patients and the frail elderly when discharged from
      hospital, as regards quality of life, compliance, costs, medical consumption and
      quality of care. In pursuit of this goal, 17 publications on the effects of
      aftercare after discharge from hospital were examined. A systematic assessment of
      methodological quality by two blinded independent reviewers resulted in a
      consensus score (0-100 points), based on four categories: the study population,
      description of the interventions, measurement of the outcome and the analysis and
      presentation of the data. Only three of the 17 studies scored more than 50
      points, indicating that most of the studies were of poor methodological quality.
      The most prevalent methodological problems were that co-interventions were not
      avoided, a placebo group was lacking, the assessment was not blinded and the
      analysis was not made on the basis of the intention-to-treat principle. The
      majority of the studies did not report clear beneficial effects in favour of the
      intervention group. The positive effects reported were limited to costs and
      quality of care.

PMID- 9637338
TI  - A case study analysis of nurses' roles, education and training needs associated
      with patient-focused care.
AB  - A case study analysis of a trust hospital piloting patient-focused care (PFC) on
      two wards was undertaken with a view to determining the education and training
      needs of registered nurses. The impact of PFC on the roles of the nurses was
      examined and nurses' perceptions of their training needs, and the extent to which
      these have been met was explored. The competency model which has been
      operationalized to meet the training needs was also determined. Twenty-three
      members of staff were interviewed including members of the project team, care
      leaders (registered nurses), managers and trainers, and various documents were
      examined. Multi-skilling of staff has so far been limited to nurses. The cross
      training programme developed, which is far from complete, is based on a model of
      competence which focuses on specific task skills. It is suggested that an
      'output' model of competence which focuses on the whole work role may be more
      appropriate for qualified nurses vested with the co-ordination of care in
      accordance with multi-disciplinary protocols. In addition, given that a whole
      range of 'soft skills' are needed to manage the changing role boundaries,
      Spencer's model of competency is also an appropriate model to adopt for the
      identification of superior performance from both care leaders and clinical
      managers. Implications for both pre- and post-registration education and training
      are highlighted. Inadequate resourcing is currently a major weakness which could
      jeopardize the entire project which otherwise is viewed very favourably by the
      majority of those who participated in this study.

PMID- 9637339
TI  - Down-regulation of tumor necrosis factor-alpha, moderate reduction of interleukin
      1beta, but not interleukin-6 or interleukin-10, by glucan immunomodulators
      curdlan sulfate and lentinan.
AB  - The effects of glucan-based immunomodulators curdlan sulfate (CRDS) and lentinan
      on cytokine production stimulated by lipopolysaccharide (LPS) in bacillus
      Calmette-Guerin (BCG)-primed mice were investigated. Pretreatment with CRDS or
      lentinan before LPS administration induced a striking inhibition of up to 89% of
      circulating tumor necrosis factor-alpha (TNF), a moderate reduction of 25% of
      interleukin (IL)-1beta, no significant differences in IL-6 or IL-10 levels, and a
      marked depression of chemiluminescence activity. Animals receiving CRDS prior to
      infection with alpha-hemolysin positive Escherichia coli inhibited measurable TNF
      production by 63%. The ability of CRDS and lentinan to significantly reduce the
      TNF production in vivo indicates the potential of glucans in possible therapeutic
      strategies that are based on down-regulation of TNF.

PMID- 9637340
TI  - Polygenic control of the expression of biological activities of an antitumor
      polysaccharide, lentinan.
AB  - Genetic studies were carried out on two in vivo responses of lentinan, delayed
      type-acute phase responses (DT-APR) and vascular dilation and hemorrhage (VDH).
      Linkage analyses showed that DT-APR was controlled by two recessive genes, ltnr1
      and ltnr2, which were mapped on chromosome 3 and 11, respectively. VDH was also
      found to be controlled by polygenes. One dominant major gene, Ltnr3, and three
      dominant minor genes, Ltnr4, Ltnr5, and Ltnr6, were mapped on chromosomes 6, 9,
      15 and 16, respectively.

PMID- 9637341
TI  - The use of recombinant adeno-associated viral vectors for the transduction of
      epithelial tumor cells.
AB  - Using hight-titer recombinant adeno-associated viral vectors (rAAV), we have
      investigated the feasibility of cancer vaccines from tumor explants. In a first
      set of experiments, rAAV vectors expressing firefly luciferase reporter genes
      were used to transduce different human tumor cell lines. At day three post
      transduction, all of the human tumor cell lines tested showed high levels of
      luciferase expression. To further evaluate rAAV-mediated gene transfer efficiency
      into primary tumor cells, we transduced freshly isolated tumor cells from
      malignant melanoma and ovarian carcinoma patients. As a remarkable result,
      reporter gene expression in primary tumor cells was significantly higher than in
      the tested established tumor cell lines. These data could also be reproduced with
      a rAAV/lacZ vector, since the portion of successfully transduced primary tumor
      was higher than 90%. Taken together, our data demonstrate that rAAV-mediated gene
      transfer is a very efficient method for the transduction of freshly isolated
      human tumor cells and may allow the generation of potent autologous cancer
      vaccines.

PMID- 9637342
TI  - Biomarkers for predicting response to regional chemo-immunotherapy in liver
      metastases from colorectal carcinoma.
AB  - Differences in therapeutic outcomes after regional chemotherapy or chemo
      immunotherapy in liver metastases from colorectal carcinoma cannot be explained
      only by variations in the regimens of treatment. This study was undertaken to
      assess the potential of several tumor-associated markers of biological behavior
      (biomarkers) to predict therapeutic response in order to pre-select the best
      candidates for this demanding treatment. In a group of 21 patients, flow
      cytometric DNA ploidy provided the most accurate prediction, with a response rate
      of 88% in 8 DNA diploid tumors compared to 31% in 13 DNA aneuploid cases (P =
      0.017) and a difference in overall survival of nine months (20.4 vs 11.3, P =
      0.041). Only a slight trend towards improved response rate was observed when we
      immunohistochemically detected p53 anti-oncoprotein expression in 11 (52%) p53
      positive tumors (P = 0.063). Other immunohistochemical biomarkers as P
      glycoprotein (p170), p21/WAF, mdm2, c-erbB-2, and proliferative activity of tumor
      (detected either by anti-PCNA and anti-Ki67 monoclonal antibodies or as a flow
      cytometric proliferation index) were unrelated to the outcome of treatment. DNA
      ploidy and expression of p53 protein are potential biomarkers for predicting the
      response to regional chemotherapy of liver metastases from colorectal carcinoma.

PMID- 9637343
TI  - Clinical study of the effect of the preparation DEODAN on leukopenia, induced by
      cytostatics.
AB  - The aim of the study is to establish the effect of the preparation DEODAN on
      leukopenia induced by chemotherapeutics in oncological patients. DEODAN is an
      oral preparation, obtained from lyzozyme lysates of Lactobacillus bulgaricus
      strain "I. Bogdanov patent strain tumoronecroticance B-51" ATCC 21815, called
      shortly LB51. In the study there are included two groups of patients--from
      National Oncological Centre, Sofia, the other from Clinic of Medicine, Bertha
      Academic Hospital, Clinics of Duisburg, Duisburg. All the patients, (78) have
      undergone combined chemotherapy. In all patients, leukopenia has been established
      in moderate and medium levels. The scheme of the application of DEODAN has been 3
      g, three times a day before meals, from the first day of establishing the
      disturbances of the haemopoesis. The treatment lasted until the restoration of
      the haematological values. Only DEODAN was applied. The results obtained show
      that the recovery of the WBC count (values above 3000) took place in all of the
      patients between days 3 and 5. None of the patients displayed any infectious or
      febrile complications, as a result of the applied chemotherapy and the treatment
      with the preparation. DEODAN also improves the general condition of the patients.

PMID- 9637344
TI  - Preclinical studies with prothymosin alpha1 on mononuclear cells from tumor
      patients.
AB  - The immunomodulating potential of the thymic protein prothymosin alpha1 (Pro
      alpha1) on the lymphocyte and monocyte directed antitumor reactions of melanoma
      and colorectal tumor patients in comparison with healthy controls were studied in
      vitro. On average, tumor patients showed lower NK- and LAK-cell activities than
      healthy controls, being associated with a lower adhesion capacity to tumor target
      cells. The NK-cell activity of the tumor patients was inversely related to the
      tumor stage. Pro alpha1 stimulated the impaired patients LAK-cell activity only
      at an early stage of disease. The Pro alpha1 effects were associated with an
      increased adhesion of lymphocytes to tumor target cells and an increased
      secretion of deficient IFN-gamma and IL-2 secretion. By flow cytometry, Pro
      alpha1 in combination with IL-2 increased the NK-cell marker CD56, CD16/56 and
      CD25 as well as CD18/11a adhesion molecule expression. Monocytes from tumor
      patients showed deranged tumoristatic activities compared with healthy controls.
      Pro alpha1 elevated the mean of the antitumor activity, when applied alone or in
      combination with rIFN-gamma. In the presence of IFN-gamma, Pro alpha1 stimulated
      the adhesion of monocytes to cultured tumor cells, mainly by increasing CD54
      expression. Pro alpha1 stimulated alone or in combination with IFN-gamma the TNF
      alpha and IL-1beta secretion by monocytes and decreased the high PGE2 and TGF
      beta level, especially in the patients groups. Perspectively, this may provide
      the basis for applying Pro alpha1 in selected antitumor immunotherapy protocols.

PMID- 9637345
TI  - Natural and synthetic thymic peptides as therapeutics for immune dysfunction.
AB  - Natural thymic peptides have been isolated from calf thymus by mild acid
      extraction. Pharmaceutical containing natural peptides (Thymalin) was put into
      practice as immunocorrector. One of the immunomodulatory molecules (L-Glu-L-Trp)
      has been isolated from Thymalin by reversed-phase high performance liquid
      chromatography. Pharmaceutical containing this agent (Thymogen) was designed on
      the base of synthesized dipeptide. A novel immunomodulatory dipeptide was
      synthesized and termed Vilon. Both natural and synthetic pharmaceuticals
      activated T-cell differentiation, T-cell recognition of peptide-MHC complexes,
      induced the changes in intracellular composition of cyclic nucleotides and
      cytokine [interleukin (IL-2), interferon (IFN)] excretion of blood lymphocytes.
      Synthetic dipeptides activated neutrophil chemotaxis and phagocytosis. They had
      no influence on antioxidant response in thymocytes in comparison with natural
      peptides. Thymalin and Thymogen were used in persons with chronic pathology and
      immune dysfunction. The results indicate that thymic peptides participate in the
      regulating mechanisms of inflammatory processes as cytokine antagonists and show
      the difference between natural and synthetic products. It is important for the
      drugs designed to prevent immune dysfunction development.

PMID- 9637346
TI  - Morphological and pharmacological evidence for the existence of brain regulatory
      circuits in the immune response.
AB  - Muramyl dipeptide (MDP) has a variety of biological effects including the effect
      on CNS, such a promotion of sleep, fever, analgesic effect or some behavioural
      changes and of course a very potent effect on immune system. The latter effect is
      at least partly mediated through the structure in CNS. With the small
      electrolytic lesions which were placed in brain from the spinal cord through the
      brain stem up to the cerebral cortex we have identified a number of structures
      such as medial frontal cortex (area Cg1-Cg3), subnucleus basomedialis and
      centralis of amygdala, subnucleus medialis and dorsolateralis of nucleus
      parabrachialis, lateral part of reticular formation (monoaminergic groups A1-7)
      and the part of the reticular formation (serotonergic groups B6-B8) which are
      evidently involved in the immunomodulatory and immunoadjuvant effect of muramyl
      dipeptide. The results of experiments also suggest that the interaction between
      neuroendocrine and immune systems might take place on the level of some of above
      mentioned anatomical structures.

PMID- 9637347
TI  - Modulation of neutrophil apoptosis by psychological stress and glucocorticoid.
AB  - Neutrophils play a pivotal role in host defense against bacterial infection,
      however, these cells may have a harmful effect on normal tissues under certain
      pathological conditions. We demonstrate here that apoptosis of these cells is
      modulated by psychophysical stress and its related hormones, suggesting that
      psychoneural systems may exert an effect on host defense through modulating
      neutrophil survival.

PMID- 9637348
TI  - Airway hyperresponsiveness: first eosinophils and then neuropeptides.
AB  - Airway hyperreactivity to bronchoconstrictor mediators is a main characteristic
      in the majority of asthmatic patients and correlates well with the severity of
      the disease. The airways of asthmatic patients are characterized by an
      inflammatory state resulting in activation of lung tissue cells and attraction
      and infiltration of leukocytes from the blood. The accumulation of eosinophilic
      leukocytes is a prominent feature of inflammatory reactions that occurs in
      allergic asthma. The increase in number of eosinophils is important since it
      correlates in time with an increase in bronchial hyperresponsiveness. Viral
      respiratory infections can also induce eosinophilia and airway
      hyperresponsiveness in humans and animals and can worsen asthmatic reactions.
      This report reviews current opinions on the relationship between inflammation
      induced eosinophil accumulation/activation and the development of airway
      hyperresponsiveness and the possible role for sensory neuropeptides in this
      process. Firstly, CC chemokines play an important role in allergic airway
      inflammation and respiratory viral infections leading to eosinophil recruitment.
      Secondly, it can be concluded that IL5 is involved in the development in airway
      hyperresponsiveness. IL5 has profound effects on eosinophils as promoter of
      growth, differentiation and proliferation, chemoattractant, activator and primer.
      However, it is conceivable that in animal models for allergic asthma besides IL5
      other regulatory mediators may be involved in eosinophil migration and activation
      in the lung, which in turn will lead to airway hyperresponsiveness. Recent data
      support the possible role of eotaxin and its eosinophil-specific receptor CCR-3
      in eosinophil chemotaxis and activation in allergic asthma. Moreover, it is
      suggested that the development of airway eosinophilia in vivo involves a two-step
      mechanism, elicited by eotaxin and IL5. The precise mechanism by which
      eosinophils induce bronchial hyperresponsiveness is at present unknown. Sensory
      neuropeptides could be important mediators in this process, since it has been
      demonstrated that airway nerves are surrounded by and infiltrated with
      eosinophils after antigen challenge. Sensory neuropeptides could be the final,
      more downstream, common pathway after eosinophil infiltration and activation in
      inducing airway hyperresponsiveness due to allergen inhalation or respiratory
      viral infections. In conclusion, in the process of the development of airway
      hyperresponsiveness observed during viral infections or in allergic asthma, the
      IL5/eotaxin-induced infiltration and activation of eosinophils in the airways is
      evident. Following this step, eosinophil-derived inflammatory mediators will
      induce the release of sensory neuropeptides (possibly NK2-receptor activating
      tachykinins) which in turn will lead to airway hyperresponsiveness.

PMID- 9637349
TI  - Neuropeptides in the immunomodulation: substance P-induced stimulation of immune
      response in mice.
AB  - The effects of substance P (SP) and its new structural analog EC-1 administered
      systemically to CBA mice on the immune responsiveness have been examined. Three
      main findings are presented in this study. First, the principal effect of SP and
      EC-1 on the immunity is a stimulatory one. It is shown that in the doses of 1, 10
      and 100 mkg/kg of the body weight both neuropeptides significantly increased the
      number of plaque- and rosette-forming cells in the spleen of animals at the peak
      of the immune reactions. Second, the destruction of the pituitary stalk prevented
      the immune response stimulation caused by neuropeptides. Third, SP-induced
      immunostimulation was not observed after combination with the antagonist of the
      postsynaptic dopamine (DA) D-2 receptors haloperidol (2 mg/kg) suggesting the
      involvement of the DAergic system in the realization of this effect. Thus, these
      results demonstrate neurochemical DAergic mechanisms underlying the
      immunostimulating influence of tachykinins.

PMID- 9637350
TI  - Modulation of the immune response by changing neuromediator systems activity
      under stress.
AB  - The possible correction of the immune response affecting the mechanisms of
      neuroimmunomodulation in the animal model of immobilization stress is considered.
      Immobilization (3 h on the back) of CBA mice caused a suppression of the immune
      response. The number of plaque-forming cell (PFC) on the 4th day as well as
      rosette-forming cell (RFC) number on the 5th day of the immune reaction to sheep
      red blood cells (SRBC) were found to be reduced as compared to the control.
      Immunoinhibition in the stressed mice was reversed by the depletion of the
      cerebral serotonin (5-HT) with p-chlorophenylalanine (PCPA) 2 days before
      immobilization at a dose of 500 mg/kg. Activation of postsynaptic D-1 and D-2
      dopamine (DA) receptors with apomorphine administered 30 min before stress
      attenuated stress-induced immunosuppression as well. Thus, the immunosuppression
      elicited by a stressor can be modified by drugs influencing the 5-HT and DAergic
      systems. It is suggested that the stress-provoked alterations of the immune
      response can be a consequence of changing neurochemical pattern of the brain and
      the disturbances of the mechanisms of psychoneuroimunomodulation.

PMID- 9637351
TI  - The immunomodulator OM-89 induces ACTH and glucocorticoid secretion in rats
      through an IL-1 dependent pathway.
AB  - The immunomodulator OM-89 (bacterial extract from E. coli), known to act on the
      immune system by modulating both humoral and cellular responses, significantly
      increases ACTH and glucocorticoids secretion in normal Wistar rats. A comparative
      administration of IL-1 displays a similar pattern of release. Moreover, OM-89
      induced responses are blocked by IL-1ra, the soluble receptor antagonist of IL-1.
      The effect of OM-89 can thus be explained, at least in part, via IL-1 which
      directly enhances the secretion of both stress hormones. Finally, a comparative
      experiment between control and stressed rats (by immobilization) shows that the
      responses to OM-89 measured in this study (ACTH and corticosterone secretion) are
      stress-modulated.

PMID- 9637352
TI  - Bacterial cell wall components as immunomodulators--I. Lipopeptides as adjuvants
      for parenteral and oral immunization.
AB  - We investigated the immunostimulatory properties of synthetically prepared
      lipopeptides derived from the cell wall of Gram negative bacteria. These
      compounds constitute potent macrophage activators and polyclonal B-lymphocyte
      stimulators. They are also immunoadjuvants in parenteral or oral immunization. By
      coupling the lipopeptides to haptens or low molecular weight antigens which are
      not immunogenic per se, highly immunogenic conjugates can be prepared.
      Lipopeptide antigen conjugates as synthetic vaccines give protection by enhancing
      the antibody-mediated immune response, and they stimulate the cellular immune
      response in vivo by priming of cytotoxic T-cells.

PMID- 9637353
TI  - Bacterial cell wall components as immunomodulators--II. The bacterial cell wall
      extract OM-85 BV as unspecific activator, immunogen and adjuvant in mice.
AB  - The bacterial extract Broncho-Vaxom used for the prevention and treatment of
      recurrent respiratory tract infections is an immunomodulator in vitro and in
      vivo, as determined in a murine model. The extract acts, on the one hand, as
      macrophage activator and polyclonal B-lymphocyte stimulant. On the other hand,
      after repeated intraperitoneal or oral immunizations, the extract is immunogenic,
      inducing serum IgG binding to the bacterial strains used for the preparation of
      the extract. On bacteria, the sera recognize the cell wall components porin,
      lipoprotein/lipopeptide and murein. The bacterial extract also exhibits adjuvant
      properties when applied in mixture with antigens, such as TNP-BSA or an influenza
      vaccine preparation. The unspecific and the immunospecific stimulatory effect of
      the extract as well as its adjuvant properties could be of importance for
      understanding its therapeutic effect.

PMID- 9637354
TI  - In vivo study on the immunomodulating effects of OM-85 BV on survival,
      inflammatory cell recruitment and bacterial clearance in Klebsiella pneumonia.
AB  - Oral administration of the bacterial extract OM-85 BV has been shown to prime
      alveolar macrophages (AM) in such a way that they secrete significantly more
      nitric oxide, tumor necrosis factor-alpha and interleukin-1beta upon in vitro
      stimulation with lipopolysaccharide (LPS). As increased cytokine secretion by AM
      may account for the therapeutic effect of OM-85 BV in respiratory tract
      infections, we studied the effect of orally administered OM-85 BV on the outcome
      of Klebsiella pneumoniae-induced pneumonia. Mice received a daily oral dose of OM
      85 BV (350 mg/kg body weight) for 5 days and were intratracheally infected with
      333, 1000 or 3333 CFU K. pneumoniae on day 8. It was shown that OM-85 BV
      pretreatment of mice has no effect on bacterial clearance, neutrophil recruitment
      and survival in this acute respiratory tract infection. Also, OM-85 BV treatment
      had no protective effect in a recurrent infection with K. pneumoniae. It is
      concluded that AM activation by oral treatment with OM-85 BV is not sufficient to
      play a protective role in respiratory tract infection with K. pneumoniae.

PMID- 9637355
TI  - Antirheumatic E. coli extract OM-89 induces T cell responses to HSP60 and 70.
AB  - Oral administration of E. coli extract OM-89 is used in treating RA. It has been
      shown that immune reactivity to heat-shock proteins (hsp) is involved in
      immunomodulation of arthritis. We evaluated the postulated presence and
      immunogenicity of hsp's in OM-89. The effects of OM-89 in experimental arthritis
      were analyzed. Proliferative T cell responses to bacterial hsp60 and hsp70 were
      found in rats immunized with OM-89. And conversely, immunization with hsp
      antigens induced OM-89-specific T cell responses. Hsp70 (DnaK) was found to be a
      major immunogenic constituent of OM-89. Parenteral immunization with OM-89
      reduces resistance to adjuvant arthritis (AA), whereas oral administration
      protects against AA. Given the arthritis inhibitory effect of oral OM-89 in AA
      our findings suggest peripheral tolerance induced by hsp-specific regulatory T
      cells as a mode of action for OM-89 as an arthritis suppressive oral drug.

PMID- 9637356
TI  - Oral dosing of rats with OM-89 results in the appearance of specific OM-89
      antibodies of the IgG2a isotype: possible significance in the treatment of
      rheumatoid arthritis.
AB  - OM-89 is a glycoprotein-rich extract of Escherichia coli shown to be effective in
      the treatment of rheumatoid arthritis (RA). It has been reported that oral dosing
      of animals results in the appearance of specific OM-89 antibodies. In the current
      study we have investigated some of the immunoglobulin isotypes that may be
      involved. OM-89 antibodies of IgG1, IgG2a and IgM isotypes were measured by ELISA
      in serum from rats dosed three times a week for 3 weeks at 4 or 40 mg kg(-1). The
      results showed a small but significant rise in IgM and a greater rise in IgG2a.
      The possibility that antigens within OM-89 (e.g. hsp65) may have homology with
      antigens involved in RA raises the possibility that OM-89 antibodies,
      particularly of the IgG2 class, may block pathogenic antigens from being
      recognized by T cells.

PMID- 9637357
TI  - Intervention in autoimmune diabetes by targeting the gut immune system.
AB  - BB rats and nonobese diabetic (NOD) mice spontaneously develop autoimmune insulin
      dependent diabetes and serve as models for human type I diabetes. During
      progression of the disease the cytokine pattern elaborated by islet infiltrating
      immune cells shifts from a Th2 or Th0 toward Th1 type. Only the latter is
      associated with "destructive" insulitis. We discuss here attempts to modulate
      disease progression by targeting the gut immune system with bacterial
      immunostimulants. Oral dosing of diabetes prone BB rats with lipopolysaccharide
      (LPS) or the Escherichia coli extract OM-89 lead to a Th2-shift of pancreatic
      mRNA expression. In vitro studies showed that repeated exposure toward LPS or OM
      89 lead to downregulation of proinflammatory macrophage responses. In the NOD
      mouse, repeated oral dosing of OM-89 caused a Th2 shift in the gut cytokine gene
      expression, probably because of desensitization of macrophages and other antigen
      presenting cells. Concomitantly, diabetes prevention by oral insulin was
      improved. In conclusion, oral dosing with bacterial immunostimulants dampens Th1
      type immune reactivities of the gut immune system and thereby promotes oral
      tolerance mechanisms. Downregulation of proinflammatory immune reactivities by
      repeated exposure to bacterial stimulants requires intact desensitization
      mechanisms in macrophages or other antigen presenting cells.

PMID- 9637358
TI  - Molecular mechanisms of the immunosuppressive action of cyclosporin A.

PMID- 9637359
TI  - Immunomodulatory properties of antiviral acyclic nucleotide analogues: cytokine
      stimulatory and nitric oxide costimulatory effects.
AB  - Acyclic nucleotide analogues exhibit strong activity against a broad range of
      viruses, including HIV-1 and -2. We have investigated their effects on in vitro
      secretion of cytokines and production of nitric oxide (NO) by murine peritoneal
      macrophages, factors known to play a role in virus replication. Included in the
      study were the most prominent compounds of the series: 9-(2
      phosphonomethoxyethyl)adenine, 9-(2-phosphonomethoxyethyl)-2,6-diaminopurine, the
      (R)- and (S)-enantiomers of 9-(2-phosphonomethoxypropyl) adenine [(R)- or (S)
      PMPA], (R)- and (S)-enantiomers of 9-(2-phosphonomethoxypropyl)-2,6-diaminopurine
      [(R)- or (S)-PMPDAP], 9-(2-phosphonomethoxyethyl)guanine (PMEG), and (S)
      enantiomer of 1-(3-hydroxy-2-phosphonomethoxypropyl)cytosine [(S)-HPMPC]. PMEG,
      (R)-PMPA, and (S)-PMPA greatly enhanced the secretion of both tumour necrosis
      factor-alpha (TNF-alpha) and interleukin-10 (IL-10), (R)-PMPDAP stimulated only
      TNF-alpha, other test compounds were ineffective. None of them influenced the
      secretion of IL-2 or interferon-gamma (IFN-gamma). Both TNF-alpha and IL-10 have
      been found to be major factors determining enhancing effects of PMEG, (R)-PMPA,
      and (S)-PMPA on production of NO generated by exogenous IFN-gamma. The study
      points to a possible implication of immunomodulatory properties in the antiviral
      effects of some acyclic nucleotide analogues. In addition, our data support the
      view that endogenous IL-10 can stimulate certain macrophage functions.

PMID- 9637360
TI  - Possible dual role of nitric oxide in oxidative stress injury: a study in
      perfused hepatocytes.
AB  - Nitric oxide (NO) is a multifunctional messenger in many vertebrates. In the
      liver, NO was found to play an important but controversial role in injury
      produced by toxins or sepsis. The purpose of the present investigation was to
      further characterize the role of NO in hepatocyte oxidative injury. A cellular
      system formed of immobilized and perfused rat hepatocytes was used to test the
      ability of the latter to produce endogenous NO after lipopolysaccharide
      administration in vivo (LPS, 20 mg/kg i.p.) and how hepatocyte functionality
      competence is modified according to NO level. This cellular system also was used
      to delineate a relationship between exogenously delivered NO to the perfusion
      medium as produced by the NO donor, sodium nitroprusside (2.0 and 0.2 mM), and
      any alteration in the degree of injury as evoked by anoxia/reoxygenation or
      cumene hydroperoxide (1.0 mM and 0.2 mM). Rat hepatocytes were immobilized in low
      gelling agarose and perfused with Williams E medium. Endogenous or exogenous NO
      was evaluated by measuring the end products of NO (NO2- + NO3-) in the perfusion
      medium. Functional integrity of hepatocytes was evaluated from lactate
      dehydrogenase (LD) leakage, urea synthesis in the perfusion medium and lipid
      peroxides (LP) formation. Normal, anoxia/reoxygenation or cumene hydroperoxide
      injured hepatocytes did not exhibit measurable NO while LPS-treated hepatocytes
      produced NO. Apparently, within the present experimental conditions, it seems
      that there was an inverse relation between the rate of NO produced after LPS
      administration and the rate of lipid peroxides formed in the hepatocytes. Low
      concentration of sodium nitroprusside (as NO donor) significantly decreased LD
      leakage, increased the rate of urea synthesis and increased trypan blue exclusion
      by hepatocytes in anoxia/reoxygenation or cumene hydroperoxide injured (0.2 mM)
      cells. Lipid peroxides were decreased by NO in cumene hydroperoxide injured
      hepatocytes. The present data suggest that NO endogenously produced, or
      exogenously delivered, has an ameliorative role in mild oxidative liver injury
      models, but not in severe cases and that inside hepatocytes, there is a very
      delicate balance between the rate of NO production and its consumption. The
      disturbance in this balance may be responsible for injury due to the formation of
      more toxic oxygen species.

PMID- 9637361
TI  - Glucan as stimulator of hematopoiesis in normal and gamma-irradiated mice. A
      survey of the authors' results.
AB  - Glucan, a beta-1,3-linked polyglucose derived from the yeast Saccharomyces
      cerevisiae, is a broad spectrum enhancer of host defense mechanisms stimulating
      humoral and cell-mediated immunity. On the basis of these features, glucan has
      been tested by the authors' research group in experiments on gamma-irradiated
      mice. Two glucan forms, particulate and soluble, have been studied. Attention has
      been focused on various application regimens in relation to the time of
      irradiation (pre- or postirradiation application), the possibilities of using
      glucan in various radiation regimens (single or repeated irradiation), combined
      pharmacological therapy (joint administration of glucan with cystamine or
      inhibitors of prostaglandin synthesis), and on the negative side effects of
      therapy with glucan. Some studies included also experiments on unirradiated mice.
      The results have demonstrated the ability of glucan to influence positively the
      course of the acute radiation disease. Stimulation of hematopoiesis has been
      found to be the most important mechanism of glucan's radioprotective effects. In
      this communication, the results of 11 full-length articles are summarized and
      discussed.

PMID- 9637362
TI  - Stimulation of haemopoiesis and protection of mice against radiation injury by
      synthetic analogues of muramyldipeptide incorporated in liposomes.
AB  - Protection from undesirable effects of radiotherapy or chemotherapy, primarily
      from myelosuppression, remains still a crucial problem to be studied. Attention
      has been therefore paid to various immunomodulatory agents that through the
      monocyte/macrophage system induced production of cytokines, which can induce and
      operate restoration of haemopoiesis and thus act radioprotectively. Some
      synthetic analogues of MDP free of undesirable side-effects, were synthesized in
      the Czech Republic. Lipophilic beta-D-GlcNstearoyl-(1- > 4)-norMurNAc-L-Abu-D
      isoGln (DDD-St) was designed to be easily entrapped into liposomes and this
      liposomal DDD-St protected efficiently mice against irradiation, when
      administered i.p., i.v. or s.c. 24 h prior to lethal irradiation (survival rate
      in the range of 30-80% compared with 0% in control). Especially the subcutaneous
      application of liposomal DDD-St was very efficient. The parameters characteristic
      of recovery of haemopoiesis in bone marrow on day 10 after 6.5 Gy irradiation
      were significantly improved in comparison with the controls. Very high
      radioprotective effect of s.c. administered liposomal DDD-St can be explained
      (together with induction of haemopoiesis) by an effective and long-lasting
      activation of nonspecific immunity, which is able to withhold an onset of
      septicemia in early days after irradiation. In conclusion, the liposomal DDD-St
      should be therapeutically beneficial in moderating the haemopoietic damage, which
      is an undesirable effect of radiotherapy or chemotherapy.

PMID- 9637363
TI  - Hugh Alistair Reid OBE MD: investigation and treatment of snake bite.
AB  - Alistair Reid was an outstanding clinician, epidemiologist and scientist. At the
      Penang General Hospital, Malaya, his careful observation of sea snake poisoning
      revealed that sea snake venoms were myotoxic in man leading to generalized
      rhabdomyolysis, and were not neurotoxic as observed in animals. In 1961, Reid
      founded and became the first Honorary Director of the Penang Institute of Snake
      and Venom Research. Effective treatment of sea snake poisoning required specific
      antivenom which was produced at the Commonwealth Serum Laboratories in Melbourne
      from Enhydrina schistosa venom supplied by the Institute. From the low frequency
      of envenoming following bites, Reid concluded that snakes on the defensive when
      biting man seldom injected much venom. He provided clinical guidelines to assess
      the degree of envenoming, and the correct dose of specific antivenom to be used
      in the treatment of snake bite in Malaya. Reid demonstrated that the non-clotting
      blood of patients bitten by the pit viper, Calloselasma rhodostoma [Ancistrodon
      rhodostoma] was due to venom-induced defibrination. From his clinical experience
      of these patients, Reid suggested that a defibrinating derivative of C.
      rhodostoma venom might have a useful role in the treatment of deep vein
      thrombosis. This led to Arvin (ancrod) being used clinically from 1968. After
      leaving Malaya in 1964, Alistair Reid joined the staff of the Liverpool School of
      Tropical Medicine, as Senior Lecturer. Enzyme-linked immunosorbent assay (ELISA)
      for detecting and quantifying snake venom and venom-antibody was developed at the
      Liverpool Venom Research Unit: this proved useful in the diagnosis of snake bite,
      in epidemiological studies of envenoming patterns, and in screening of antivenom
      potency. In 1977, Dr H. Alistair Reid became Head of the WHO Collaborative Centre
      for the Control of Antivenoms based at Liverpool.

PMID- 9637364
TI  - Characterization of mastoparan-induced histamine release from RBL-2H3 cells.
AB  - Mastoparan (5-30 microM), a tetradecapeptide isolated from wasp venom, caused
      histamine release from RBL-2H3 cells in a concentration- and time-dependent
      manner. Mastoparan-induced histamine release remained after removing the
      extracellular Ca2+, whereas the antigen-induced one disappeared. Pertussis toxin
      did not inhibit mastoparan-induced histamine release from the cells, and
      mastoparan did not stimulate phosphoinositide hydrolysis. In agreement with the
      results, RBL-2H3 cells had a small amount of ADP-ribosylation substrates for
      pertussis toxin. Neomycin (1-5 mM) suppressed mastoparan-induced histamine
      release and phospholipase D activation. However, butanol slightly inhibited
      mastoparan-induced histamine release. Moreover, 2,3-diphosphoglycerate inhibited
      mastoparan-induced phospholipase D activation, but not it's histamine release. On
      the other hand, mastoparan caused the leakage of lactate dehydrogenase from the
      cells in a similar concentration range to the histamine release. This leakage was
      also suppressed by neomycin. These results suggest that mastoparan enhances the
      membrane permeability, resulting in histamine release in a pertussis toxin
      insensitive manner, and that mastoparan-induced phospholipase D activation may
      not relate to histamine release.

PMID- 9637365
TI  - Characterization of three fibrinogenolytic enzymes from Chinese green tree viper
      (Trimeresurus stejnegeri) venom.
AB  - From the venom of Chinese green tree viper (Trimeresurus stejnegeri), three
      distinct fibrinogenolytic enzymes: stejnefibrase-1, stejnefibrase-2 and
      stejnefibrase-3, were purified by gel filtration, ion-exchange chromatography and
      reverse-phase high-performance chromatography (HPLC). SDS-PAGE analysis of those
      three enzymes showed that they consisted of a single polypeptide chain with mol.
      wt of 50000, 31000 and 32000, respectively. Like TSV-PA (a specific plasminogen
      activator) and stejnobin (a fibrinogen-clotting enzyme) purified from the same
      venom, stejnefibrase-1, -2 and -3 were able to hydrolyze several chromogenic
      substrate. On the other hand, different from TSV-PA and stejnobin, stejnefibrase
      1, -2 and -3 did not activate plasminogen and did not possess fibrinogen-clotting
      activity. The three purified enzymes directly degraded fibrinogen to small
      fragments and rendered it unclottable by thrombin. Stejnefibrase-2 degraded
      preferentially Bbeta-chain while stejnefibrase-1 and -3 cleaved concomitantly
      Aalpha and Bbeta-chains of fibrinogen. None of these proteases degraded the gamma
      chain of fibrinogen. When correlated with the loss of clottability of fibrinogen,
      the most active enzyme was stejnefibrase-1. The activities of the three enzymes
      were inhibited by phenylmethylsulfonyl fluoride (PMSF) and p-nitrophenyl-p
      guanidinobenzoate (NPGB), indicating that like TSV-PA and stejnobin, they are
      venom serine proteases.

PMID- 9637366
TI  - Role of free thiol groups in the biological activities of stonustoxin, a lethal
      factor from stonefish (Synanceja horrida) venom.
AB  - Stonustoxin (SNTX) is a two-subunit protein purified from the venom of a
      stonefish, Synanceia horrida. It has potent lethal activity and is also a
      membrane pore-forming cytolysin. The role of thiol groups in the biological
      activities of SNTX was investigated. Both the hemolytic and lethal activities of
      SNTX were potentiated by the reducing agent, dithiothreitol (DTT). The hemolytic
      activity of SNTX was sensitive to the modification of thiol groups by 5,5'
      dithiobis(2-nitrobenzoic acid) (DTNB). The loss of haemolytic activity correlated
      with the number of thiol groups that were titrated with DTNB. Thiol modification
      of SNTX with DTNB also inhibited its lethality. These inhibitory effects of thiol
      modification could be reversed by reduction with DTT. It was also found that the
      haemolytic activity of SNTX could not be inhibited by cholesterol. These
      observations indicate that free thiol groups play an important role in the
      haemolytic activity and lethality of SNTX but unlike other thiol-activated
      cytolysins, SNTX was not inhibited by cholesterol. Thus, SNTX may represent a new
      class of cytolytic toxin.

PMID- 9637367
TI  - Isolation and partial characterisation of highly toxic lectins from Abrus
      pulchellus seeds.
AB  - The seeds of Abrus pulchellus, sub-specie tenuiflorus, belonging to the
      Leguminosae, subfamily Papilionoideae contain highly toxic lectins exhibiting
      specificity for galactose and galactose-containing structures. The toxins which
      agglutinate rabbit erythrocytes, present a highly toxic activity in vivo when
      injected in the peritoneal cavity of mice (LD50=31 microg x kg(-1)) or when
      tested with the microcrustacean Arthemia salina (LD50=3.5 microg x ml(-1)). The
      active fraction was purified in a single step, by affinity chromatography on a
      Sepharose-4B column. The purified toxins migrated as two single bands of Mr 63000
      and 61500 Da (SDS-PAGE) and Mr 31500 and 29000 Da (SDS-PAGE with 2
      mercaptoethanol), respectively, suggesting the presence of disulphide-bridge
      interchains as occurs in other plant toxins. The antibodies anti-A. pulchellus
      toxins did not recognize ricin preparation and only partial identity was observed
      to A. precatorius toxic lectins prepared in a similar way to ricin and A.
      pulchellus toxins.

PMID- 9637368
TI  - Structural characterization of a new acylpolyaminetoxin from the venom of
      Brazilian garden spider Nephilengys cruentata.
AB  - The use of mass spectrometry, in which high-energy CID and charge remote
      fragmentation both of protonated and sodium-attached molecular ions was applied,
      afforded the structural elucidation of a new acylpolyaminetoxin with Mw=801 Da
      from the venom of the Brazilian garden spider Nephilengys cruentata. In spite of
      having the same Mw of the NPTX-2, previously described in the venom of the Joro
      spider Nephila clavata, neither toxins are isomers. In order to differentiate
      them by using the most usual nomenclature, the new toxin was named NPTX-801C and
      the NPTX-2 was renamed to NPTX-801E. Both toxins have as common structure the 4
      hydroxyindole-3-acetyl-asparaginyl-cadaveryl moiety in their molecules and their
      structure may be represented in a simplified way: NPTX-801E is HO-indole-Asn-Cad
      Pta-Orn-Arg and NPTX-801C is HO-indole-Asn-Cad-Gly-Put-Pta-Pta.

PMID- 9637369
TI  - Effects of Russell's viper venom on renal lysosomal functions in experimental
      mice.
AB  - The lysosome-enriched fraction of mice kidney was isolated by homogenization and
      differential centrifugation. Lysosomal functions, namely lysosomal enzyme
      activities and membrane integrities were investigated in (a) the renal lysosome
      enriched fraction, incubated with different concentrations of Russell's viper
      venom (RVV) for various time intervals (in vitro test) and (b) the kidney
      homogenate of mice, which had been envenomed with different dosages of RVV and
      been sacrificed after various time intervals post-envenomation (in vivo test).
      Three typical marker enzymes for lysosome were used, namely N-acetyl-beta-D
      glucosaminidase (NAG), cathepsin D and acid phosphatase. It was found that, with
      increasing dosages of RVV and increasing time intervals after RVV treatment, the
      activities of all lysosomal enzymes generally increased and the lysosomal
      membrane integrities apparently reduced in in vitro and in vivo conditions,
      respectively. Among the three typical marker enzymes, NAG was found to be the
      most specific, sensitive and informative marker enzyme for the study of lysosomal
      functions in the kidney of mice treated with RVV.

PMID- 9637370
TI  - A rapid procedure for the isolation of the Lys-49 myotoxin II from Bothrops
      moojeni (caissaca) venom: biochemical characterization, crystallization, myotoxic
      and edematogenic activity.
AB  - Bothtrops moojeni snake venom was fractionated on a CM-Sepharose column which was
      previously equilibrated with 0.05 M ammonium bicarbonate buffer at pH 8.0 and
      subsequently eluted with an ammonium bicarbonate concentration gradient from 0.05
      to 0.5 M at constant pH (8.0) and temperature (25 degrees C). The fraction which
      eluted last (M-VI) showed, after direct lyophilization, a single band by
      polyacrylamide gel electrophoresis (PAGE) and SDS-PAGE, indicating an approximate
      Mr of 14000 and 27000, in the presence and absence of dithiothreitol,
      respectively. Its amino acid composition revealed a high level of hydrophobic and
      basic amino acids as well as 14 half-cystine residues. Its isoelectric point and
      extinction coefficient (E(1.0 mg/ml) (1.0 cm) at 278 nm and pH 7.0) were 8.2 and
      1.170, respectively. M-VI was devoid of phospholipase A2 (PLA2) activity on egg
      yolk, as well as of hemorrhagic, anticoagulant and coagulant activities, but
      could induce drastic necrosis on skeletal muscle fibres as well as rapid and
      transient edema on the rat paw. Its N-terminal sequence:
      SLFELGKMILQETGKNPAKSYGVYGCNCGVGGRGKPKDATDRCCYVHKCCYK... revealed high homology
      with other Lys 49 PLA2-like myotoxins from other bothropic venoms. Orthorhombic
      crystals of M-VI, which diffracted to a maximal resolution of 1.6 A, were
      obtained and indicated the presence of a dimer in the asymmetrical unit.

PMID- 9637371
TI  - Transmission of the paralytic shellfish poisoning toxins, from dinoflagellate to
      gastropod.
AB  - Purple clams, Hiatula diphos Linnaeus, are filter-feeding bivalves and maculated
      ivory shells. Babylonia areolata Link are carnivorous gastropods. Both
      shellfishes are popular seafood delicacies among the Taiwanese. Hiatula diphos
      were forced to contain gonyautoxins (GTXs) in this research by feeding them with
      cells of Alexandrium minutum Halim, a toxic dinoflagellate species responsible
      for the paralytic shellfish poisonings in Taiwan. The intoxicated purple clams of
      known toxicity and toxin composition were fed to B. areolata to observe the
      transmission and transformation of GTXs among this shellfish. It was found that
      the toxin composition in bivalve and gastropod were similar to that in
      dinoflagellate. Our data provide evidence for food-chain transmission of
      paralytic shellfish poisoning toxins, from dinoflagellate to gastropod through a
      filter-feeding bivalve. The transmitted GTX-I. -II. -III and -IV of A. minutum
      could only be found in the viscera of these shellfish. There was a notable
      degradation of GTX-I in the ivory shell that resulted in a decrease in toxicity
      while the total amount of toxins was accumulatively increasing.

PMID- 9637372
TI  - The involvement of plasma kinins in the cardiovascular effects of Leiurus
      quinquestriatus scorpion venom in anaesthetised rabbits.
AB  - The present study was undertaken to investigate the involvement of kinins in the
      cardiovascular- and respiratory effects of LQQ venom. Blood pressure, heart rate,
      electrocardiogram (ECG) and respiration were studied in anaesthetised rabbits, in
      the presence and absence of aprotinin and icatibant, a B2 bradykinin antagonist.
      Plasma bradykinin concentrations were also measured following venom injection.
      LQQ venom caused a triphasic effect on blood pressure comprising an immediate
      fall, a pronounced rise and a progressive decline until death. Bradycardia,
      myocardial damage, arrhythmias, respiratory distress and pulmonary oedema were
      also exhibited. Pretreatment with aprotinin attenuated the venom-induced
      hypotension, bradycardia, ECG and respiratory changes and prolonged survival.
      Pretreatment of atropinized animals with icatibant gave similar protection. In
      animals treated with LQQ venom, plasma bradykinin was significantly higher than
      controls, although there was considerable inter-animal variation in plasma kinin
      concentrations and the elevation was seen relatively late after venom
      administration. The data provides some support for the hypothesis that kinins are
      involved in the cardiovascular and lethal effects of LQQ venom in rabbits.

PMID- 9637373
TI  - Sphingomyelinase D activity of brown recluse spider (Loxosceles reclusa) venom as
      studied by 31P-NMR: effects on the time-course of sphingomyelin hydrolysis.
AB  - The time-course for the hydrolysis of the D linkage of chicken egg yolk
      sphingomyelin in a Triton X-100 mixed micelle and of lysophosphotidylcholine
      micelles, as catalyzed by brown recluse spider venom and brown recluse spider
      toxin, was followed by phosphorous-31 nuclear magnetic resonance spectroscopy.
      The overall rate of hydrolysis of sphingomyelin in mixed micelles was found to be
      an order of magnitude faster than the hydrolysis of lysophosphotidylcholine.
      Incorporation of lysophosphotidylcholine into mixed micelles with Triton X-100
      inhibited the lipase activity of brown recluse spider venom and brown recluse
      spider venom toxin. The effects of increased rates of overall reaction were
      observed with increased temperature and also with decreased ionic strength. The
      presence of divalent calcium ions was found to be necessary for hydrolytic
      activity, but only in catalytic amounts (less than 1 mM).

PMID- 9637374
TI  - Crystallization of piratoxin I, a myotoxic Lys49-phospholipase A2 homologue
      isolated from the venom of Bothrops pirajai.
AB  - Large single crystals of piratoxin I. a Lys49-PLA2 homologue with low enzymatic
      activity, have been obtained. The crystals belong to the orthorhombic system
      space group P2(1)2(1)2(1), and diffract X-rays to a resolution of 2.8 A.
      Preliminary analysis reveals the presence of two molecules in the
      crystallographic asymmetric unit.

PMID- 9637375
TI  - Bibliography of toxinology.

PMID- 9637376
TI  - Welfare of the competition horse.

PMID- 9637377
TI  - International disease surveillance: summary of outbreaks of the major diseases in
      Europe in 1997.

PMID- 9637378
TI  - Determination of the frequency and distribution of vascular and parenchymal
      amyloid with polyclonal and N-terminal-specific PrP antibodies in scrapie
      affected sheep and mice.
AB  - Brains from 17 histopathologically confirmed cases of scrapie, five of which had
      congophilic vascular amyloid, were stained immunohistochemically for prion
      protein (PrP) using a polyclonal antibody. Two clinically suspect but
      pathologically unconfirmed cases of natural sheep scrapie and the brains of four
      mice infected with the 111A murine scrapie strain were also examined. Selected
      sections containing amyloid were stained with each of two peptide antibodies
      which recognise the N-terminal amino acid residues which are lost following
      protease digestion of the disease-specific isoform of PrP. The mice infected with
      the 111A murine scrapie strain had large numbers of hypermature plaques. All the
      amyloid plaques from both natural sheep scrapie brains and experimental murine
      brains were heavily immunostained by the polyclonal and both peptide antibodies.
      In addition, disease-specific accumulations of PrP were detected in endothelial
      cells or in the intima of blood vessels of the cerebral cortex of sheep scrapie
      brains. The affected blood vessels were located in areas which otherwise lacked
      typical scrapie pathology. Vascular accumulations of PrP were also found in
      leptomeningeal and choroid plexus blood vessels. Vascular amyloid was found
      mainly in the neocortex. Vascular amyloid and disease-specific parenchymal
      accumulations of PrP were found in two sheep which showed clinical signs of
      scrapie but lacked its typical vacuolar pathology. These results show that the
      mature amyloid of scrapie is composed of, or contains a substantial proportion
      of, whole length PrP protein. Thus truncation of PrP is not essential for the
      aggregation of PrP into amyloid. The vascular amyloid of natural sheep scrapie
      originates from the accumulation and release of PrP from endothelial cells
      presumably following systemic scrapie infection. The topography of vascular
      amyloid distribution in Great Britain differs from that reported in the
      Netherlands. As amyloid deposition in mice is largely controlled by the strain of
      the infecting agent it is possible that the strain of the agent may influence
      vascular amyloid deposition.

PMID- 9637379
TI  - Haemorrhagic smolt syndrome: a severe anaemic condition in farmed salmon in
      Scotland.
AB  - Farmed pre-smolt stage Atlantic salmon developed an acute, severe haemorrhagic
      anaemia, termed haemorrhagic smolt syndrome. The fish were in good condition, but
      lethargic, and had widespread visceral and muscle petechiation and ecchymoses.
      The mean (sd) haematocrit of affected fish was 1.4(0.9) per cent and
      histopathology revealed widespread haemorrhage in all organs, associated with
      endothelial tissue. No infectious agent was isolated and the condition could not
      be transmitted experimentally. The clinical evidence indicates that the condition
      is non-infectious, but its aetiology could not be fully established.

PMID- 9637380
TI  - Comparison of detomidine/ketamine and guaiphenesin/thiopentone for induction of
      anaesthesia in horses maintained with halothane.
AB  - This prospective clinical study compared the physiological effects of two
      commonly used anaesthetic induction techniques in horses maintained with
      halothane. One hundred horses admitted for elective surgery were randomly
      allocated to receive either guaiphenesin (to effect) and thiopentone (5 mg/kg),
      or detomidine (20 microg/kg) and ketamine (2 mg/kg) for the induction of
      anaesthesia after acepromazine premedication. Anaesthesia was maintained with
      halothane in oxygen. There were no significant differences in breed, age, sex,
      weight, type of surgery and duration of anaesthesia between the groups.
      Immediately after induction of anaesthesia heart rate was higher after
      guaiphenesin and thiopentone, and arterial blood pressure was higher after
      detomidine and ketamine. Thereafter hypotension, often necessitating an infusion
      of dobutamine, developed in both groups. Arterial blood gases and respiratory
      rates were similar in the two groups. There were no significant differences
      between the groups in the subjectively scored quality of induction and recovery,
      or in recovery time.

PMID- 9637381
TI  - Assessing abattoir hygiene with a marker organism.
AB  - A study was made to evaluate the use of a marker organism for assessing whether
      hygienic slaughter practices were being followed at red meat abattoirs. The
      organism, a nonpathogenic strain of Escherichia coli K12 that was resistant to
      nalidixic acid, was detected and counted on a highly specific isolation medium.
      With beef carcases, the practice of bagging the excised anus reduced, but did not
      prevent the spread of the organism from an inoculum applied in the anal region
      before the hide was removed. The carcases of sheep that were processed at a low
      throughput abattoir, were contaminated with the marker after the fleece had been
      inoculated at a single site. The contamination was significantly reduced
      (P<0.001) when the operative responsible for flaying had cleaned his hands, arms
      and apron before and during the handling of each carcase, and used a knife which
      was freshly pasteurised on several occasions. However, the subsequent washing of
      carcases had little or no effect on the levels of the marker organism. It was
      concluded that the marker may be of value in assessing hygiene control, improving
      present practices, and training abattoir staff.

PMID- 9637382
TI  - Diabetes mellitus in dogs: a study of the critical difference for canine serum
      fructosamine.
AB  - The purpose of this study was to calculate the critical difference between two
      analytical measurements of serum fructosamine concentration in dogs. The critical
      difference can be used to judge whether the difference between two consecutive
      analytical results from the same animal is due to natural variation. Blood
      samples from 15 apparently clinically healthy beagle dogs were collected once a
      week for six consecutive weeks. The serum fructosamine concentration was measured
      by the reduction test with nitroblue tetrazolium and the critical difference was
      calculated from the component of variance for weeks within dogs (sigma2s) and the
      residual variance (sigma2e). The critical difference between two consecutive
      analytical results was 33.5 micromol/litre.

PMID- 9637383
TI  - Warble fly status of Great Britain in 1997.

PMID- 9637384
TI  - Salinomycin toxicity in layer breeders.

PMID- 9637385
TI  - Treatment of a uterine adenocarcinoma in a domestic rabbit by ovariohysterectomy.

PMID- 9637386
TI  - Nasal mite of dogs Pneumonyssus (Pneumonyssoides) caninum in Iran.

PMID- 9637387
TI  - Staffing at veterinary schools.

PMID- 9637388
TI  - Staffing at veterinary schools.

PMID- 9637389
TI  - Staffing at veterinary schools.

PMID- 9637390
TI  - Influence of sample collection on bulk tank somatic cell count.

PMID- 9637391
TI  - Gas gangrene in a horse.

PMID- 9637392
TI  - Aorto-iliac thrombosis in calves.

PMID- 9637393
TI  - Fumes from gas boilers.

PMID- 9637394
TI  - Veterinary Benevolent Fund.

PMID- 9637395
TI  - Protective effect of deferoxamine on sodium nitroprusside-induced apoptosis in
      PC12 cells.
AB  - Reportedly, the generation of nitric oxide (NO) may lead to iron mobilization
      from ferritin disrupting intracellular iron homeostasis and increasing levels of
      reactive oxygen species. In the present study, we evaluated the role of
      endogenous iron in NO-induced apoptosis in PC12 cells. Apoptosis was tested by
      flow cytometry, fluorescence microscopy and terminal deoxynucleotidyl transferase
      mediated 2'-deoxy-uridine 5'-triphosphate nick end labeling (TUNEL) technique.
      Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay. When incubated with 0.5-0.75 mM sodium
      nitroprusside (SNP, a chemical NO donor), PC12 cells were shown to undergo
      apoptosis. In addition, SNP induced a time-dependent decrease in cell viability.
      Since deferoxamine (0.05-0.1 mM), a powerful iron chelator, inhibited both SNP
      induced apoptosis and the decrease in cell viability, we suggest that these NO
      effects may be dependent upon iron mobilization within the cell.

PMID- 9637396
TI  - Comparable activity levels in developmentally deprived and non-deprived layer IV
      cortical columns of the adult rat primary somatosensory cortex.
AB  - It has been suggested that evoked neural activity levels promote the selective
      construction of the primary somatosensory cortex (S1) neuropil. Sensory
      deprivation after S1 formation has, however, no effects on its postnatal growth.
      This indicates that S1 neuropil elaboration is independent from the ongoing
      levels of evoked cortical activity, and/or that sensory deprivation does not
      reduce overall levels of S1 evoked activity. We thus indirectly evaluated chronic
      and acute levels of neural activity in the developmentally, sensory deprived
      adult S1. Relative succinic dehydrogenase activity and 3H2-deoxyglucose uptake
      were comparable in control and deprived barrels. Our observations support the
      idea that normal levels of evoked neural activity prevent atrophic changes in the
      developmentally deprived adult S1. They can not rule out, however, that early
      selective S1 neuropil construction occurs independent from evoked neural activity
      levels.

PMID- 9637397
TI  - Increased dentate granule cell neurogenesis following amygdala kindling in the
      adult rat.
AB  - Structural neuronal network plasticity is associated with epileptogenesis during
      limbic kindling, but the full extent of network changes is not well understood.
      We investigated whether dentate granule cell (DGC) neurogenesis, which continues
      into adulthood in the rodent, is altered in the amygdala kindling model of
      epileptogenesis. Adult rats were stimulated to either 4-6, 9-10 or 19-20 class
      4/5 (generalized) kindled seizures. 5-Bromo-2'-deoxyuridine labeling showed that
      cell proliferation increased in the dentate gyrus only in animals that
      experienced nine or more class 4/5 kindled seizures. Immunocytochemistry for
      neuronal markers revealed that many of the newly generated cells differentiated
      into DGCs in the inner aspect of the DGC layer. The lack of increased DGC
      neurogenesis after fewer kindled seizures or at early timepoints following
      kindling suggests that this process is not involved in kindling development.
      Instead, newly generated DGCs may be important for maintenance of the kindled
      state or the increased susceptibility to spontaneous recurrent seizures.

PMID- 9637398
TI  - Self-sustained firing of human motor units.
AB  - Motoneurons of invertebrates and vertebrates can continue to fire repetitively
      after being activated by a brief, excitatory synaptic input (self-sustained
      firing). This firing behavior is due to the activation of intrinsic, voltage
      gated currents which produce sustained regenerative depolarizations (plateau
      potentials) of the cell. Examination of these intrinsic cellular properties has
      been performed in reduced animal preparations and it is unknown if such self
      sustained firing occurs in motoneurons of the intact human. In this paper, we
      present evidence of this in the human by using a technique of dual motor unit
      recordings. Subjects were instructed to maintain a constant dorsiflexion effort,
      and the common synaptic input (e.g. descending drive) onto the tibialis anterior
      (TA) motoneuron pool was monitored by recording the firing frequency of a low
      threshold 'control' unit. Once the firing rate of the control unit was constant,
      vibration of the TA tendon recruited a second 'test' unit which continued to fire
      after the vibration (i.e. synaptic input) was removed, even though the firing
      rate of the control unit (and thus, the common drive) remained the same or
      decreased. Self-sustained firing of motoneurons such as this may reduce the need
      for prolonged synaptic input when constant muscle activation is required (e.g.
      for postural tone).

PMID- 9637399
TI  - Postischemic treatment with calpain inhibitor MDL 28170 ameliorates brain damage
      in a gerbil model of global ischemia.
AB  - The newly-developed calpain inhibitor, MDL 28170 penetrates the blood-brain
      barrier and inhibits brain cysteine protease activity after systemic
      administration. This experiment was initiated to determine if the calpain
      inhibitor, MDL 28170 could, by these actions, reduce neuronal damage in an animal
      model of global cerebral ischemia in the gerbil. The calpain inhibitor, MDL 28170
      (50 mg/kg), was initiated at 0.5 and 3 h of recirculation following 5min of
      global ischemia. Animals subjected to ischemia but without treatment or with
      vehicle treatment served as controls. Evaluation by light microscopy was carried
      out on paraffin-embedded brain sections of gerbils which were sacrificed 7 days
      post-operatively. The results show that the calpain inhibitor, MDL 28170,
      protects against cortical neuronal damage even if the treatment is delayed until
      3 h after reperfusion. However, the neuroprotective effect of this agent is less
      pronounced in the hippocampal CA1 sector. The results suggest that calpain
      mediated proteolysis plays an important role in neuronal death due to ischemia.
      However, additional mechanisms by which an increased intracellular calcium
      concentration leads to neuronal death may exist.

PMID- 9637400
TI  - Chemokine inhibition in rat stab wound brain injury using antisense
      oligodeoxynucleotides.
AB  - Traumatic injury to the central nervous system (CNS) results in the breakdown of
      the blood-brain barrier and recruitment of hematogenous cells at the site of
      injury. The role of chemokines in this process has been well recognized and they
      have been regarded as promising targets for development of anti-inflammatory
      therapies. The expression of monocyte chemoattractant protein (MCP-1), in
      particular, has been closely linked to macrophage infiltration following trauma
      in rat brain. In this study we determined whether inhibition of MCP-1 following
      stab wound injury would reduce macrophage infiltration. Stab wound injured
      Sprague-Dawley rats were infused with MCP-1 sense or antisense oligonucleotides
      using an Alzet miniosmotic pump (1 microl/h for 3 days). Three days following
      injury, widespread gliosis was observed in both groups of rats as judged by glial
      fibrillary acidic protein (GFAP) immunoreactivity. Immunohistochemistry showed
      significantly less staining for MCP-1 in antisense treated animals. In addition,
      the number of macrophages were reduced by 30% in the antisense compared to the
      sense treated animals (P < 0.05). These results demonstrate that modulation of
      MCP-1 expression in stab wound injury directly affects monocytic infiltration and
      provide a basis for MCP-1 inhibition as a therapeutic strategy for controlling
      inflammatory events of traumatic brain injury.

PMID- 9637401
TI  - Intracerebral source localization of mental process-related potentials elicited
      prior to mental sweating response in humans.
AB  - We measured the mental sweating response (MSR) and the skin sympathetic nerve
      activity (SSNA). Mental arithmetic or recall questions first elicited SSNA and
      then elicited MSR. MSR was used as the trigger point of time 0 ms to average
      EEGs. The averaged EEGs contained slow wave fluctuations, which occurred 5 s
      prior to the MSR onset. The current source locations of the MSR-related
      potentials were estimated by EEG dipole tracing method in two subjects. Mental
      stress activated the inferior frontal gyrus 5.5 s prior to the MSR and then 0.5 s
      later, the lateral part of the hippocampus in a subject, and they activated the
      medial part of the amygdala 5 s prior to the MSR in another subject. Indirect
      contact of the brain with the mind associated with mental questions was
      discussed.

PMID- 9637402
TI  - Stochastic determination of the chromosomal region responsible for expression of
      human glial fibrillary acidic protein in astrocytic tumors.
AB  - Previous investigators have localized the human glial fibrillary acidic protein
      (GFAP) gene in the segment 17q21 in chromosome 17. In the present study, we
      statistically assessed the association between the allelic status in thirty-three
      microsatellite loci and the immunohistochemical expression of GFAP in twenty
      human astrocytic tumors. The results demonstrated that the loss of heterozygosity
      in only one locus (D17S795 located in 17q21.2) was significantly associated with
      the impaired expression of GFAP (P = 0.0280, Pc = 0.0384 by Fisher's exact test).
      The adjacent loci located in 17q21.1 and 17q21.3 were not relevant to GFAP
      expression. Those data suggest that the critical region responsible for GFAP
      expression (coding sequence and regulatory elements) is located close to the
      locus D17S795 in the segment 17q21.2.

PMID- 9637403
TI  - Low density lipoprotein receptor related protein gene exon 3 polymorphism
      association with Alzheimer's disease in Chinese.
AB  - Since apolipoprotein E4 (apoE4) is the major genetic risk for late onset
      Alzheimer's disease (AD), proteins that interact with apoE might be involved in
      AD pathogenesis. Low density lipoprotein receptor related protein (LRP) is an
      apoE receptor in the brain. In exon 3 of the LRP gene a polymorphism was found to
      be underrepresented in AD compared to normal Caucasian subjects (N). We examined
      this polymorphism in Chinese AD and N subjects. The polymorphism frequency in N
      was roughly half that reported for Caucasians. Compared to N, the frequency was
      significantly decreased in pathologically diagnosed, but not in clinically
      diagnosed AD patients. Thus, the role of the LRP exon 3 polymorphism in AD has
      now been demonstrated in two ethnic groups, suggesting the importance of LRP in
      AD pathogenesis.

PMID- 9637404
TI  - NMDA-induced increases in rat brain glutamine synthetase but not glial fibrillary
      acidic protein are mediated by free radicals.
AB  - Both excitotoxicity and oxidative stress are implicated in the pathophysiology of
      central nervous system (CNS) ischaemia-reperfusion injury whereby astrocytes
      offer neural protection through the production of endogenous antioxidants and
      removal of glutamate from the extracellular milieu. This study investigated
      whether exogenous alpha-tocopherol, an antioxidant, could prevent N-methyl-D
      aspartate (NMDA)-produced increases of the glial specific proteins, glutamine
      synthetase (GS) and glial fibrillary acidic protein (GFAP) in rat brain spheroids
      in vitro. NMDA (320 microM; 3 days in vitro (DIV)) was unable to induce lipid
      peroxidation in rat brain spheroids implying that excitotoxicity in this system
      did not involve substantial free radical formation. However at non-cytotoxic
      concentrations, increases in astroglial GS were prevented by alpha-tocopherol
      treatment, suggesting a role for ROS in the excitotoxic process. In contrast,
      NMDA-induced increases in GFAP remained unchanged by alpha-tocopherol indicating
      that oxidative stress may not be involved in reactive gliosis at non-cytotoxic
      NMDA concentrations.

PMID- 9637405
TI  - Bilaterally independent respiratory rhythms in the decerebrate rat.
AB  - In rats, respiratory neurons in the medulla oblongata are arranged in
      longitudinally distributed groups that are duplicated on each side of the
      neuraxis. Our aim was to determine whether respiratory rhythm is generated
      independently by each side. We made a complete mid-sagittal section of the
      medulla oblongata, 3.5 mm rostral and 3.5 mm caudal to the obex, in decerebrate,
      vagotomized, and paralysed adult rats. Respiratory rhythm, monitored by recording
      the activity of both left and right phrenic nerves, was maintained and became
      asynchronous between the left and right sides. We concluded that in the adult rat
      each half of the medulla oblongata is capable of generating respiratory rhythm
      independently.

PMID- 9637406
TI  - High frequency of apolipoprotein E epsilon 2 allele is specific for patients with
      cerebral amyloid angiopathy-related haemorrhage.
AB  - The apolipoprotein E (APOE) epsilon 2 allele is a putative risk factor for
      cerebral amyloid angiopathy-related haemorrhage. We explored the frequency of the
      APOE epsilon 2 allele in intracranial haemorrhage due to three different
      pathophysiological mechanisms to determine the specificity of the association.
      APOE genotypes in 207 autopsies with intracranial haemorrhage (96 subarachnoid
      haemorrhage, 71 deep intracerebral haemorrhage, 40 cerebral amyloid angiopathy
      (CAA)-related haemorrhage patients) were compared with 41 autopsy controls
      without neuropathological abnormalities and 406 living patients admitted to
      hospital following head injury. As identified previously the epsilon 2 allele
      frequency was significantly over-represented in CAA-related haemorrhage
      (frequency 0.24, P < 0.01); this association was stronger among patients with
      multiple CAA-related haematomas (0.31). The epsilon 2 frequencies of the deep
      haemorrhage (0.13) and subarachnoid haemorrhage (0.09) groups were not
      significantly different from the control autopsies (0.07) or live patients
      (0.08). The findings indicate that the epsilon 2 allele is associated with
      haemorrhage only in the context of cerebral blood vessels laden with amyloid.

PMID- 9637407
TI  - Beta-actin immunoreactivity in rat microglial cells: developmental pattern and
      participation in microglial reaction after kainate injury.
AB  - In the present study we investigated the developmental and post-injury pattern of
      beta-actin immunoreactivity in rat brain. Our data suggest that beta-actin is
      higher in microglia-macrophages than in any other central nervous system cell
      type, including neurons and astrocytes. We also show that beta-actin
      immunoreactivity is particularly high in ameboid-macrophagic cells, suggesting a
      role on the plastic changes that these cells experience during maturation or
      after activation.

PMID- 9637408
TI  - pH dependency of mu-calpain and m-calpain activity assayed by casein zymography
      following traumatic brain injury in the rat.
AB  - Studies employing casein zymographic assays analyzed the effects of varying pH
      (from pH 6.8 to pH 8.0) on changes in mu-calpain and m-calpain activity in naive,
      sham-injured and injured rat cortex 3 h following unilateral cortical impact
      injury. Mu-calpain activity following cortical impact injury was enhanced between
      pH values of 7.2 and 7.8, with pH 7.5 being optimal. m-Calpain activity was
      readily detected only between pH values of 7.2 and 7.4, with pH 7.3 producing the
      most prominent proteolytic activity. These observations suggest that strict
      control of pH is an important consideration in assessments of brain pH activation
      by casein zymography. Moreover, activation of different calpain isoforms,
      especially after traumatic brain injury, may be differentially influenced by
      smaller changes in physiological pH than previously recognized.

PMID- 9637409
TI  - Expression of T lymphocyte adhesion molecules: regulation during antigen-induced
      T cell activation and differentiation.
AB  - The pattern of lymphocyte traffic and migration in vivo is a composite of
      constitutive recirculation and transient changes induced by interaction with
      antigen. Naive T lymphocytes in their basal, unstimulated state continuously
      recirculate throughout the entire host, poised to react to specific antigens that
      they are programmed to recognize. After interaction with antigen, T cell traffic
      changes, first with the trapping of reactive cells in antigen-containing lymphoid
      tissue. Subsequently, the effector cells responding to antigen, accompanied by
      nonspecific T cells and monocytes, traffic in large numbers to sites of antigen
      localization, resulting in the localized inflammatory response. Then, as the
      immune response wanes, memory T cells develop, many of which exhibit still
      different routes of recirculation. The traffic and tissue localization of
      leukocytes is regulated by a series of cell surface adhesion molecules that
      recognize specific ligands on endothelial cells and in the extracellular matrix.
      Modulation of the expression of these adhesion molecules results in the changes
      in T cell traffic that are characteristic of each stage of T cell
      differentiation. Thus, during T cell activation and differentiation, the down
      regulation of adhesion receptors specific for lymphoid tissue endothelium and up
      regulation of integrins facilitate the targeting of effector cells to sites of
      inflammation. Subsequent changes in adhesion receptors regulate the traffic of
      the antigen-specific memory cells. T cell adhesion molecule expression is
      therefore regulated as a function of the stage of activation and differentiation
      and, in addition, is influenced by cytokines and the local lymphoid
      microenvironment.

PMID- 9637410
TI  - IL-2-induced cellular events.
AB  - In this review we discuss several molecules that are attractive candidates as
      transducing molecules involved in signaling processes. IL-2 receptor signaling is
      a complex process involving a large number of molecules: Ras, Rho, PI3 kinase,
      PKC, Akt, transcription factors NF-AT, and NF-kappaB and some target genes such
      as bcl-2, c-myc, c-jun and c-fos. Ras and Rho have been defined as dual molecules
      because Ras- and Rho-initiated signals can either promote or inhibit apoptosis.
      Several studies have contributed to the delineation of a signaling pathway
      structured in three independent channels designated channels 1, 2, and 3. These
      three channels serve as major landmarks: Lck-c-fos/c-jun (channel 1), Syk-myc
      (channel 2), and a pathway leading to actin organization/bcl-2 expression
      (channel 3). The detailed hierarchical organization of these three channels is
      presented throughout the review and the model is depicted in the figure.

PMID- 9637411
TI  - Expression and function of recombination activating genes in mature B cells.
AB  - Recombination activating genes, RAG-1 and RAG-2, encode proteins that catalyze
      the rearrangement of immunoglobulin genes in B cells and T cell receptor genes in
      T cells to generate the diversity of these important recognition molecules in
      immune system. It has been believed that these gene rearrangements occur
      exclusively in premature stages of B and T lymphocytes, consistent with the
      observation that RAG expression is downregulated in mature lymphocytes. However,
      recent studies have revealed that even mature B cells in peripheral lymphoid
      tissues can reexpress RAG-1 and RAG-2 proteins following immunization.
      Strikingly, RAG-expressing B cells are localized in the germinal centers (GCs) of
      secondary lymphoid tissues in which somatic hypermutations, isotype switching,
      and affinity maturation of antibodies take place. Recently, it has been shown
      that RAG proteins thus induced are functional and can mediate the secondary
      rearrangement of Ig genes (receptor editing) at mature stages of B cells.
      Evidence is accumulating suggesting that GCs are regarded as a primary lymphoid
      tissue. In the present review, we briefly summarize recent advances in the
      expression and the characterization of RAG proteins and discuss their possible
      role in mature B cells in relation to the diversification and the selection of B
      cell repertoire in GCs.

PMID- 9637412
TI  - Intraepithelial lymphocytes: origins, distribution, and function.
AB  - Intraepithelial lymphocytes (IEL) are associated with the intestinal tract,
      respiratory tract, genitourinary tract epithelium, and the skin and are the first
      immune system cells to encounter pathogens that have invaded an epithelial
      surface. IEL are predominantly T cells (CD3+) with CD8+ cells predominating at
      most, but not all, sites. Both TCR alphabeta+ and TCR gammadelta+ cells are found
      within IEL populations and an increasing body of evidence suggests that some IEL
      may arise extrathymically. The presence within intestinal IEL of cells expressing
      potentially self-reactive TCR suggests that T cell selection within epithelia may
      differ from thymic T cell selection although recent evidence suggests that these
      cells may in fact be nonresponsive. IEL exhibit various cytotoxic activities
      including alloreactive and virus-specific CTL activity, NK activity and
      spontaneous cytotoxicity, activities consistent with an immune surveillance or
      first line of defence role. IEL also appear activated in vivo and secrete a
      variety of cytokines. Subsets of IEL have been shown to provide B cell help, to
      play a role in the maintenance of oral tolerance and to regulate epithelial cell
      function. In this review the morphology, distribution and phenotype of IEL, the
      potential for extrathymic development and possible functions of this unique
      lymphoid population are discussed.

PMID- 9637413
TI  - Proteases and cell-mediated cytotoxicity.
AB  - Cytotoxic T lymphocytes and natural killer cells represent the body's primary
      defense against viral-infected and tumorigenic cells. The classically described
      mechanism by which these cells induce target cell death is granule mediated:
      cytolytic granules within the killer cell are directionally exocytozed toward the
      target cell, and the granule contents inflict a "lethal hit" on the target cell.
      A second mechanism of cytotoxicity is now known to exist, and utilizes cell
      surface receptors on the target cell, for which the ligand is expressed on the
      killer cell. Receptor oligomerization results in the recruitment of cytoplasmic
      proteins to the receptors and the transduction of a death signal to the target
      cell. In both granule- and receptor-mediated cytotoxicity, the target cell dies
      through a defined series of steps, which together are termed apoptosis. Recent
      work on apoptosis has defined a family of cysteine proteases, the caspases, which
      appear to be involved in the initiation of apoptosis in response to a number of
      stimuli. This review focuses on studies that link these proteases to target cell
      death induced by cytotoxic cells.

PMID- 9637414
TI  - Some psychosocial aspects of nonlethal chondrodysplasias: I. Assessment using a
      Life-Styles Questionnaire.
AB  - Studies concerning the psychosocial aspects of skeletal dysplasias that cause
      disproportionate short stature have been few and have usually involved small
      numbers of patients. As part of a study involving patients with chondrodysplasias
      and their families, an assessment battery of standardised instruments designed to
      measure depression, anxiety, self-esteem, personal support networks, marital
      adjustment, and family structure were completed by patients and, in many cases,
      their sibs, spouses, and/or parents. This first in a series of six papers reports
      the results of a Life-Styles Questionnaire which provides some insights into the
      levels of satisfaction with various aspects of life, including friendships,
      employment, the use of some substances and services, and the impact of the
      skeletal dysplasia on career, marriage, and childbearing. Results are presented
      for patients and the unaffected parents of patients. Overall, the study has shown
      a high level of satisfaction with many aspects of life. However, there are
      important differences in attitudes between the married and unmarried patients,
      and in some cases the unaffected parents, in a number of areas including health,
      overall satisfaction with life, and concerns surrounding child bearing and
      employment.

PMID- 9637415
TI  - Some psychosocial aspects of nonlethal chondrodysplasias: II. Depression and
      anxiety.
AB  - Individuals with chondrodysplasias may have disproportionate short stature and in
      some cases a distinctive facial appearance. These physical signs have the
      potential of affecting parent-child interactions and those of the dwarfed person
      with broader society. Depression and anxiety are two psychological symptoms with
      potential for a major impact on a person's functioning within society. In this
      study depression and anxiety were assessed using the Beck Depression Inventories
      and the Spielberger State-Trait Anxiety Inventories. While in general depression
      did not appear more likely in dwarfs than in the general population, comparison
      of adult patients with their unaffected sibs did raise some concern. Also, having
      an unaffected parent or spouse appeared to be associated with higher depression
      scores. Adult trait anxiety levels appeared higher, especially among women, than
      normally expected in the general population and when compared with their
      unaffected sibs.

PMID- 9637416
TI  - Some psychosocial aspects of nonlethal chondrodysplasias: III. Self-esteem in
      children and adults.
AB  - Self-esteem is considered one of the most important personality attributes. It
      correlates with physical and mental health and the ability to cope with stress.
      The attitudes of others, and the experiences of interacting with them, are
      considered as playing a major role in the development of self-esteem. Thus, those
      patients with disproportionate short stature due to a chondrodysplasia can
      reasonably be considered to be at risk of developing low self-esteem. In this
      study, self-concept and self-esteem were measured in 159 children and adults with
      various chondrodysplasias and disproportionate short stature. The results from
      the children did not suggest that they had a lower concept of self than did their
      unaffected sibs or a sample of average-size persons. By contrast, although the
      adults did not differ significantly from a population sample, they scored
      significantly below their unaffected sibs. There also appeared to be a trend to
      lower scores among women, patients who had had an unaffected parent, and those
      who were married to an unaffected spouse, although none of those differences were
      statistically significant.

PMID- 9637417
TI  - Some psychosocial aspects of nonlethal chondrodysplasias: IV. Dyadic scale of
      marital adjustment.
AB  - This article examines marital adjustment of couples who have had a child with
      dwarfism due to a skeletal dysplasia, and of couples where one or both members
      are dwarfs. The instrument used was the Dyadic Adjustment Scale developed by
      Spanier [1976: Marriage Family 38:15-38]. The reasons for examining this
      psychosocial aspect of dwarfism were that the birth of a dwarfed child to average
      size parents might be expected to cause stress in the relationship, and because
      several authors had raised concerns about the nature and/or quality of marriages
      involving dwarfs. This study provides evidence of a decrease in the level of
      marital adjustment for the average-size parents of affected children, gives
      tentative reassurance about marriages where both individuals are dwarfs, but
      raises some concerns about couples where only one member is a dwarf.

PMID- 9637418
TI  - Some psychosocial aspects of nonlethal chondrodysplasias: V. Assessment of
      personal social support using the Personal Resource Questionnaire.
AB  - Social support has been shown to be an important influence on how an individual
      copes with a number of stresses, including acute and chronic illness, psychiatric
      morbidity, and life events. It can be thought of as a dynamic process consisting
      of a network of persons who are available to provide support, and the level of
      support that is perceived to be available from those persons. Patients with
      disproportionate short stature due to a chondrodysplasia might be expected to
      face greater challenges in developing a social support network. This study
      assessed social support among a group of dwarfed patients using the Personal
      Resource Questionnaire (PRQ85). The overall extent and functioning of social
      support appears comparable to that in the general population, but there are some
      differences when unmarried patients are compared with married patients and when
      those who have affected spouses are compared with those whose spouses are of
      average stature.

PMID- 9637419
TI  - Some psychosocial aspects of nonlethal chondrodysplasias: VI. Assessment of
      family interaction using the FACES II Questionnaire.
AB  - Intrafamilial dynamics, including those between parents, and between parents and
      their children, have an important influence on the ultimate success or failure of
      a child's becoming a well adapted and socially integrated individual. Disability
      and/or birth defects, such as dwarfism, may alter family functioning, either
      because of the psychological impact or the day-to-day functional demands or both.
      Family cohesiveness and adaptability and communication have been identified as
      key variables that define how a family interacts. The Circumplex Model of Family
      Systems defines the role of these factors in the family dynamic and the FACES II
      scale provides a standardised assessment of their level of function within the
      family. Thus families can be classified by their degree of cohesion,
      adaptability, and the combination of the two. This article reports on the results
      of the FACES II assessment that was completed by 107 patients with
      disproportionate short stature due to a chondrodysplasia, as well as by a
      variable number of their parents, sibs, or spouses.

PMID- 9637420
TI  - Functional health status of adults with achondroplasia.
AB  - Little is known regarding the functional health status of individuals with
      achondroplasia. This cross-sectional survey of adults with achondroplasia was
      undertaken to assess the functional health status of this population and its
      determinants. The study sample consisted of members of the Little People of
      America (LPA) who completed a mailed questionnaire consisting of a demographics
      component, a general and disease-specific comorbidities component, and the Short
      Form 36 (SF-36) health status questionnaire. Univariate analyses and multivariate
      linear regression models were used for data analysis. Four hundred thirty-seven
      individuals with a mean age of 38 years completed the survey. The age- and gender
      adjusted Mental Component Summary (MCS) scores did not significantly differ from
      those of the general population. In contrast, the age- and gender-adjusted
      Physical Component Summary (PCS) scores were significantly lower than the general
      population starting in the fourth decade of life. Musculoskeletal diseases were
      most prevalent and had the greatest impact on the PCS scores. Two-thirds of this
      cohort had undergone at least one operation. Only musculoskeletal procedures were
      significantly associated with PCS and MCS scores. The functional health status of
      adults with achondroplasia, as measured by the SF-36, is not drastically reduced
      in comparison with that of the general U.S. population.

PMID- 9637421
TI  - Clinical outcomes of four patients with microdeletion in the long arm of
      chromosome 2.
AB  - We present clinical outcome, through several years of follow-up, of 4 mentally
      retarded patients, each with a small interstitial deletion in the long arm of
      chromosome 2, within a region on which clinical reports are infrequent. Our
      patient 1 was found to have del(2)(q22.3q23.3); patients 2 and 3,
      del(2)(q23.3q24.2); and patient 4, del(2) (q24.2q31). By comparison of our cases
      with each other and with those previously published with comparable interstitial
      deletion, we attempted to identify characteristic clinical findings. Short neck
      with excessive cervical skin was seen with monosomy of chromosome 2 bands q22.3
      q23.3, while hypertrichosis and a peculiar high pitched cry were seen with
      monosomy of chromosome 2 bands q23.3-q24.2. As suggested by Moller et al. [1984:
      Hum Genet 68:77-86], a cleft between the first and second toes was seen with
      monosomy of chromosome 2 bands q24.2-q31. In addition, seizure disorder was
      present in patients 1 and 4 (with the more proximal and distal deletions,
      respectively).

PMID- 9637422
TI  - De novo apparently balanced complex chromosome rearrangement (CCR) involving
      chromosomes 4, 18, and 21 in a girl with mental retardation: report and review.
AB  - We describe a complex and unique, de novo apparently balanced translocation
      involving chromosomes 4, 18, and 21 with 4 breakpoints, in a patient who was
      referred for an evaluation of possible fragile-X syndrome. Fluorescence in situ
      hybridization (FISH) confirmed the complexity of the rearrangement and showed the
      derivative 21 to be composed of 3 distinct segments derived from chromosomes 21,
      18, and 4. The derivative chromosome 18 had undergone a double translocation, the
      first such event to be described in constitutional complex chromosomal
      rearrangements (CCRs) involving chromosome 18. A review of these CCRs suggests
      the existence of a breakpoint "hot spot" on 18q21.

PMID- 9637423
TI  - 4q33-qter deletion and absorptive hypercalciuria: report of two unrelated girls.
AB  - We report on two unrelated girls with multiple malformations, each of whom had a
      der(4)t(4;?)(q33;?) chromosome--an unbalanced translocation chromosome with
      deletion of the 4q33-qter segment and addition of a segment of an unknown
      chromosome. One of the two girls had asymptomatic kidney stones. Both had excess
      urinary calcium excretion (0.53 and 0.84 mg/mg creatinine, respectively),
      exaggerated excretion on oral calcium load, and reduced but excessive excretion
      on restricted calcium intake. The urinary calcium excretion of their parents was
      normal. Both girls were thus diagnosed to have sporadic absorptive
      hypercalciuria. It was deduced that the 4q33-qter segment contains the putative
      gene for absorptive hypercalciuria.

PMID- 9637424
TI  - Interstitial Dup(1p) with findings of Kabuki make-up syndrome.
AB  - We describe a male patient with interstitial duplication of the short arm of
      chromosome 1 with breakpoints involving 1p13.1 and 1p22.1. The patient presented
      with some clinical findings of Kabuki make-up syndrome (KMS), including mental
      retardation, small head, eversion of the lateral part of lower eyelids,
      epicanthic folds, lateral flare of the eyebrows, short columella, and persistent
      fetal finger pads. This cytogenetic finding may provide clues for gene mapping of
      the syndrome.

PMID- 9637425
TI  - Mutational analysis of the DTDST gene in a fetus with achondrogenesis type 1B.
AB  - We describe a diastrophic dysplasia (DTDST) gene mutation in a Japanese male
      fetus with achondrogenesis type 1B and his relatives. Diagnosis in the fetus was
      based on roentgenographic data and pathological findings of bones and cartilage.
      Nucleotide sequencing of the DTDST gene demonstrated that the fetus was
      homozygous for both delVal340 and Thr689Ser and his parents and a healthy brother
      were heterozygous for the mutations. The former mutation was reported previously
      in patients with achondrogenesis type 1B, and the latter was detected in 5
      alleles of 26 healthy Japanese individuals. These data suggest that delVal340 is
      associated with achondrogenesis type 1B in the Japanese, whereas a serine to
      threonine substitution is most likely polymorphic.

PMID- 9637426
TI  - A rare form of spondylometaphyseal dysplasia-type A4.
AB  - We present 2 cases of a previously apparently unreported spondylo-metaphyseal
      dysplasia comprising dwarfism, severe metaphyseal changes, ovoid vertebrae and
      mild platyspondyly with anterior tonguing of the vertebral bodies. The
      inheritance may be autosomal recessive.

PMID- 9637427
TI  - Duplication of distal thumb phalanx in Shwachman-Diamond syndrome.
AB  - Shwachman-Diamond syndrome (SDS) comprises of exocrine pancreatic dysfunction,
      various degree of pancytopenia, and metaphyseal dysplasia. We report on a child
      with SDS and duplication of distal thumb phalanx. This combination has not been
      reported previously. We suggest that supernumerary thumb is likely a rare
      skeletal manifestation of SDS and that SDS should be considered in the
      differential diagnosis of patients with bone marrow failure and duplication of
      the thumb along with Blackfan-Diamond/Aase syndrome and Fanconi's anemia.

PMID- 9637428
TI  - New recessive syndrome characterized by increased chromosomal breakage and
      several findings which overlap with Fanconi anemia.
AB  - We describe four cases with several findings of Fanconi anemia (FA), but without
      hypersensitivity to DNA cross-linking that is the distinguishing characteristic
      of FA. Two of the cases are male and female sibs of Hispanic origin, age 6 years
      and 11 months, respectively. Both have short stature, failure to thrive, absent
      thumbs, short palpebral fissures, and skin pigmentation abnormalities. The girl
      also has developmental "dysplasia" of her hips. Presently, both siblings are
      hematologically normal. Elevated baseline chromosome breakage was observed in the
      boy, but not in the girl. Neither sib showed elevated diepoxybutane (DEB)-induced
      chromosomal breakage. In a subsequent pregnancy, prenatal studies showed slightly
      elevated baseline and DEB induced chromosome breakage (greater than normal, but
      lower than the established range for FA). The fetus had intrauterine growth
      retardation and an absent right thumb. A review of cases referred to the
      International Fanconi Anemia Registry for DEB testing showed one additional case
      with similar findings. That patient, a girl, of Caucasian English ancestry, age
      14 years, had short stature, a history of failure to thrive, skin pigmentation
      abnormalities, absent right thumb, hypoplastic left thumb, and hydrocephalus that
      resolved spontaneously. Elevated baseline chromosome breakage was observed in
      skin fibroblasts but not in lymphocytes. We postulate that these cases represent
      a previously undescribed autosomal recessive syndrome. These and other previously
      reported cases provide evidence for alternative genetic mechanisms that may
      result in developmental anomalies similar to those seen in FA.

PMID- 9637429
TI  - Multiple schwannomas, multiple nevi, and multiple vaginal leiomyomas: a new
      dominant syndrome.
AB  - We report on a family of seven affected with a new syndrome of multiple deep
      schwannomas, multiple nevi (both intradermal and compound types), and multiple
      leiomyomas of the vagina. Inheritance is dominant, whether autosomal or X-linked
      cannot be determined at this time. The nevi, which are congenital, appear to be a
      marker for the syndrome. Both the schwannomas and leiomyomas do not manifest
      until adulthood.

PMID- 9637430
TI  - Delineation of the common critical region in Williams syndrome and clinical
      correlation of growth, heart defects, ethnicity, and parental origin.
AB  - Williams syndrome (WS) is a neurodevelopmental disorder with a variable
      phenotype. Molecular genetic studies have indicated that hemizygosity at the
      elastin locus (ELN) may account for the cardiac abnormalities seen in WS, but
      that mental retardation and hypercalcemia are likely caused by other genes
      flanking ELN. In this study, we defined the minimal critical deletion region in
      63 patients using 10 microsatellite markers and 5 fluorescence in situ
      hybridization (FISH) probes on chromosome 7q, flanking ELN. The haplotype
      analyses showed the deleted cases to have deletions of consistent size, as did
      the FISH analyses using genomic probes for the known ends of the commonly deleted
      region defined by the satellite markers. In all informative cases deleted at ELN,
      the deletion extends from D7S489U to D7S1870. The genetic distance between these
      two markers is about 2 cM. Of the 51 informative patients with deletions, 29 were
      maternal and 22 were paternal in origin. There was no evidence for effects on
      stature by examining gender, ethnicity, cardiac status, or parental origin of the
      deletion. Heteroduplex analysis for LIMK1, a candidate gene previously implicated
      in the WS phenotype, did not show any mutations in our WS patients not deleted
      for ELN. LIMK1 deletions were found in all elastin-deletion cases who had WS. One
      case, who has isolated, supravalvular aortic stenosis and an elastin deletion,
      was not deleted for LIMK1. It remains to be determined if haploinsufficiency of
      LIMK1 is responsible in part for the WS phenotype or is simply deleted due to its
      close proximity to the elastin locus.

PMID- 9637431
TI  - Gaucher type 2 disease: identification of a novel transversion mutation in a
      French-Irish patient.

PMID- 9637432
TI  - Micro stent implantation in patients with acute myocardial infarction without
      anticoagulation: clinical experience with two different antithrombotic protocols.
AB  - The 4-week outcome following Micro stent implantation for acute myocardial
      infarction was assessed with the use of two different antithrombotic regimens.
      The patients were postprocedurally treated with acetyl salicylic acid (ASA) and
      heparin for 24-48 h (Group I; n = 52), or ASA and ticlopidine plus abciximab if
      indicated (Group II; n = 52). Stent implantation was successful in 49 patients
      (94%) of group I and in 46 patients (89%) of group II (NS). Subacute stent
      thrombosis occurred in nine patients (17%) of group I and in 1 patient (2%) of
      group II (P < 0.05). There were no significant differences in the rates of
      mortality, coronary bypass operation, or vascular complications. Micro stent
      implantation in acute myocardial infarction is highly effective and associated
      with a low risk for subacute stent thrombosis if the patients are
      postprocedurally treated with ASA and ticlopidine plus abciximab if indicated.

PMID- 9637433
TI  - Comparison of quantitative coronary angiographic results after directional
      coronary atherectomy and balloon angioplasty of protected left main coronary
      stenosis.
AB  - We compared the angiographic and clinical outcomes after directional coronary
      atherectomy (DCA, 13 patients) with those after conventional balloon angioplasty
      (BA, 21 patients) in patients with protected left main coronary artery stenosis.
      The initial success rate was 100% in the DCA group and 81% (17 of 21) in the BA
      group. Restenosis was present in 2 of 11 patients in the DCA group and 9 of 16
      patients in the BA group (18% vs. 56%, P < 0.05). DCA and BA improved a minimal
      lumen diameter. The initial gain after DCA was greater than that after BA. At
      follow-up, the minimal lumen diameter was larger and the percentage diameter
      stenosis was smaller in the DCA group than in the BA group. The late loss and
      loss index were equivalent in both groups. Compared with conventional BA, DCA in
      protected left main coronary artery stenosis is associated with a higher
      angiographic success rate and provides a wider luminal diameter with reduced
      incidence of restenosis.

PMID- 9637434
TI  - Percutaneous treatment of left main disease: keys to success.

PMID- 9637436
TI  - Learning curve in the use of the radial artery as vascular access in the
      performance of percutaneous transluminal coronary angioplasty.
AB  - Radial artery access for coronary artery angioplasty is a cost-effective
      alternative to other vascular entry sites. The initial series of patients using
      the radial artery site for an operator without experience in using arm access for
      coronary artery angioplasty was evaluated. Clinical success was achieved via the
      radial artery in 87% of 32 lesions and 84% of 27 patients. The major feature
      limiting success via the arm was radial/brachial artery spasm, which occurred in
      30% of cases (clinical success: 50% with spasm vs. 95% without spasm, P < 0.05).
      Spasm was more common in patients with peripheral vascular disease and in
      hypertensive patients not treated with calcium channel blockers prior to
      angioplasty. Coronary angioplasty via the radial artery may be successfully
      performed even by the interventionalist inexperienced in arm access. Vascular
      spasm is an important feature that limits the ability successfully to complete
      coronary angioplasty via the radial artery.

PMID- 9637435
TI  - Angioplasty of totally occluded old vein grafts with new interventional
      techniques: a long-term follow-up study.
AB  - The long-term patency of saphenous vein graft (SVG) lesions after intervention
      has been shown to be improved with new interventional techniques such as stents.
      Long-term outcome of patients undergoing successful angioplasty of totally
      occluded old SVGs with new devices is unknown. From July 1994 to June 1996, 19
      patients with totally occluded old SVGs had successful angioplasty with new
      interventional techniques. Mean SVG age was 123 +/- 8 mo. Thrombolysis in
      myocardial infarction trial (TIMI) flow was 0 in all target lesions. TIMI 2 or 3
      flow was restored after angioplasty in all patients. Intracoronary urokinase,
      transluminal extractional atherectomy, and stenting were used in 14, 12, and 6
      patients, respectively. There was one in-hospital death due to ongoing myocardial
      infarction, no recurrent infarction, and no repeat angioplasty or bypass surgery
      in the hospital. At follow-up of 21 +/- 1 mo, there was one sudden death and one
      myocardial infarction. Five patients had repeat coronary bypass surgery, and 4
      had repeat angioplasty. Thirteen patients remained asymptomatic, and 4 had
      angina. The long-term outcome of patients who had successful reopening of
      occluded old SVGs is encouraging in this small sample.

PMID- 9637437
TI  - Internal mammary artery graft angioplasty: acute and long-term outcome.
AB  - Secondary to the low attrition rate of internal mammary artery grafts, limited
      data are available on the clinical and angiographic outcome of patients who have
      undergone balloon angioplasty of an internal mammary artery stenosis. This study
      examined a consecutive series of 68 patients who underwent balloon angioplasty of
      an internal mammary artery graft over a 9-year period. Procedural success was
      achieved in 60 of 68 (88%) patients. The primary reason for procedural failure
      was extreme vessel tortuosity. There were no major in-hospital complications.
      Angiographic follow-up was obtained in 78% of the patients with an angiographic
      restenosis rate of 19%. The overall event-free survival in patients with an
      initially successful procedure was 92%. In conclusion, internal mammary artery
      balloon angioplasty has both an excellent initial success rate as well as a low
      incidence of restenosis and repeat target lesion revascularization.

PMID- 9637439
TI  - Long stenting in native coronary arteries: relation between vessel size and
      outcome.
AB  - Procedural and 6-mo clinical outcomes were evaluated in 34 consecutive patients
      who had stenting (<40 mm) of a long segment of coronary artery. Procedural
      success was achieved in 32 (96%) patients. Before stenting, 32 (96%) patients had
      Canadian Cardiovascular Society Class 3 or 4 angina compared to 7 (21%) at 6-mo
      follow-up (P<0.001). Eleven patients (32%) suffered either acute/subacute stent
      thrombosis (n=4) or restenosis (n=7). On logistic regression distal reference
      diameter <2.5 mm (odds ratio 26, P<0.01) and previous cardiac intervention (odds
      ratio 9.0, P<0.01) were independent predictors of a major adverse event during
      follow-up. There was no significant association between outcome and indication
      for stenting, type of stent, or use of ticlopidine and aspirin. These results
      indicate that distal vessel diameter <2.5 mm is a powerful predictor of subacute
      thrombosis or restenosis after long coronary artery stenting.

PMID- 9637438
TI  - Comparison of thrombolytic therapy of lower-extremity acute, subacute, and
      chronic arterial occlusions.
AB  - Our purpose was to study the effectiveness of thrombolytic therapy in treating
      acute, subacute, and chronic arterial occlusions in a multicenter retrospective
      study. Intraarterial urokinase infusion was performed in 235 patients for
      occluded native arteries. There were 70 (30%) with acute and 26 (5%) with
      subacute occlusions, and 141 (59%) with chronic symptoms for longer than 3 mo.
      Complete thrombolysis was achieved in 60 (86%) of the acute, 20 (77%) of the
      subacute, and 106 (75%) of the chronic occlusions. Adjunctive interventional
      procedures were performed as needed. Long-term follow-up revealed a primary
      patency of 87%, 85%, and 76% for the acute, subacute, and chronic occlusion
      groups, respectively. We conclude that the rate of complete thrombolysis of
      chronic occlusions proved slightly more efficient for acute and virtually the
      same for subacute occlusions. Long-term follow-up demonstrated a higher failure
      rate with chronic than with acute occlusions, probably due to worsened peripheral
      vascular runoff.

PMID- 9637440
TI  - Summary of the Mayo Clinic experience with direct left ventricular puncture.
AB  - Hemodynamic assessment of patients with prosthetic valves can be challenging.
      Noninvasive techniques may be limited by interference from the prosthetic
      material, whereas access to the left ventricle for direct pressure measurements
      often is not possible using common methods. The technique of direct, percutaneous
      left ventricular puncture has been proven to be a safe method that often provides
      needed data to help manage difficult clinical situations. We report our 8-yr
      experience with this technique for assessment of patients with valvular
      prostheses. Direct left ventricular puncture is a safe technique in patients with
      prior cardiac surgery and provided significant diagnostic information in the set
      of patients with multiple valvular prostheses.

PMID- 9637441
TI  - Evaluation of the compressive mechanical properties of endoluminal metal stents.
AB  - The mechanical properties of metal stents are important parameters in the
      consideration of stent design, matched to resist arterial recoil and vascular
      spasm. The purpose of this study was to develop a system for a standardized
      quantitative evaluation of the mechanical characteristics of various coronary
      stents. Several types of stents were compressed by external hydrostatic pressure.
      The stent diameter was assessed by placing a pair of small ultrasonic sono
      crystals on the stent. From pressure-strain diagrams the ultimate strength and
      radial stiffness for each stent were determined. For all stents, except the MICRO
      II and the Wiktor stent, the diameter decreased homogeneously until an ultimate
      compressive strength was exceeded, causing an abrupt collapse. Expanded to 3 mm,
      the mechanical behavior of the beStent, the Crown and the Palmaz-Schatz stent
      (PS153-series) were comparable. The spiral articulated Palmaz-Schatz stent showed
      twice the strength (1.26 atm) of the PS-153 (0.65 atm). The NIR stent yielded a
      maximum strength of 1.05 atm. The MICRO-II and the Wiktor stent did not collapse
      abruptly but rather showed a continuous decline of diameter with increasing
      external pressure. The Cardiocoil stent behaved in a fully elastic manner and
      showed the largest radial stiffness. Difference in mechanical properties between
      stents were documented using a new device specifically developed for that
      purpose. These mechanical stent parameters may have important clinical
      implications.

PMID- 9637442
TI  - New indicator for stent covering area.
AB  - A small gap between stent struts is essential to support the vessel wall, prevent
      elastic recoil, and prevent intimal flaps from prolpasing into the lumen. We
      defined Gap Index as the ratio of strut width divided by the percent of the
      vessel wall area covered by the stent metal, and proved mathematically that this
      index relates inversely to the total length of stent struts (or coil), and
      directly related to stent cell size. Twenty-four (12 tubular and 12 coil) stents
      from 17 manufacturers were analyzed. Strut width in the tubular and coil groups
      was 354.1 +/- 276.0 and 955.9 +/- 553.9 microm, respectively (P < 0.001). The
      relative metallic surface area (RMS) in the tubular and coil groups for 3 mm
      stent diameter was 16.0 +/- 4.6 and 10.6 +/- 3.7%, respectively (P < 0.005).
      Great variations in Gap Index were found amongst different stents, with up to 100
      fold. Gap Index in the tubular and coil groups for 3 mm stent diameter was 24.4
      +/- 21.7 and 105.8 +/- 97.5 units, respectively (P = 0.001). Thus, coil stents
      have a smaller relative metallic surface area despite increased strut width. This
      is the result of reduced total strut length and fewer and larger cells, as
      represented by a higher Gap Index. This information may be useful for new stents
      designs.

PMID- 9637443
TI  - Progressive vascular remodeling and reduced neointimal formation after placement
      of a thermoelastic self-expanding nitinol stent in an experimental model.
AB  - Despite the improvements afforded by intracoronary stenting, restenosis remains a
      significant problem. The optimal physical properties of a stent have not been
      defined. We compared the vascular response to a thermoelastic self-expanding
      nitinol stent with a balloon-expandable tubular slotted stainless steel stent in
      normal porcine coronary arteries. Twenty-two stents (11 nitinol and 11 tubular
      slotted) were implanted in 11 miniature swine. The nitinol stents were deployed
      using the intrinsic thermal properties of the metal, without adjunctive balloon
      dilation. The tubular slotted stents were implanted using a noncompliant balloon
      with a mean inflation pressure of 12 atm. Intravascular ultrasound (IVUS) and
      histology were used to evaluate the vascular response to the stents. The mean
      cross-sectional area (CSA) of the nitinol stents (mm2) as measured by IVUS
      increased from 8.13 +/- 1.09 at implant to 9.10 +/- 0.99 after 28 days (P =
      0.038), while the mean CSA of the tubular slotted stents was unchanged (7.84 +/-
      1.39 mm2 vs. 7.10 +/- 1.07 mm2, P = 0.25). On histology at 3 days, the tubular
      slotted stents had more inflammatory cells adjacent to the stent wires (5.7 +/-
      1.5 cells/0.1 mm2) than the nitinol (3.9 +/- 1.3 cells/0.1 mm2, P = 0.016). The
      tubular slotted also had increased thrombus thickness (83 +/- 85 microm) than the
      nitinol stents (43 +/- 25 microm, P = 0.0014). After 28 days, the vessel injury
      score was similar for the nitinol (0.6 +/- 0.3) and the tubular slotted (0.5 +/-
      0.1, P = 0.73) designs. The mean neointimal area (0.97 +/- 0.46 mm2 vs. 1.96 +/-
      0.34 mm2, P = 0.002) and percent area stenosis (15 +/- 7 vs. 33 +/- 7, P = 0.003)
      were significantly lower in the nitinol than in the tubular slotted stents,
      respectively. We conclude that a thermoelastic nitinol stent exerts a more
      favorable effect on vascular remodeling, with less neointimal formation, than a
      balloon-expandable design. Progressive intrinsic stent expansion after implant
      does not appear to stimulate neointimal formation and, therefore, may provide a
      mechanical solution to prevent in-stent restenosis.

PMID- 9637444
TI  - Successful coronary stenting in a 4-year-old child.
AB  - This report describes a 4-yr-old with critical coronary artery stenosis acquired
      after surgery for congenital heart disease. The patient was treated successfully
      with coronary stenting after unsuccessful angioplasty.

PMID- 9637445
TI  - Percutaneous transluminal coronary angioplasty in a 30-month-old child with
      embolic long segment occlusion of the left anterior descending artery.
AB  - A 30-mo-old girl developed occlusion of her left anterior descending coronary
      artery following mitral valve replacement. She presented with refractory angina
      pectoris. Successful percutaneous transluminal coronary angioplasty of the left
      anterior descending artery was performed, resulting in restoration of flow,
      resolution of anginal symptoms, and early improvement in left ventricular
      function.

PMID- 9637446
TI  - Coronary interventions in the pediatric patients: team (adult and pediatric)
      approach.

PMID- 9637447
TI  - Retrieval of "old" foreign bodies from the cardiovascular system in children.
AB  - Several techniques have been developed to retrieve catheter and guide wire
      fragments that have embolized to the heart and pulmonary vasculature. In most
      instances, retrieval of the embolized fragments is performed soon after the event
      has occurred. In this report, we summarize our experience with the removal of
      these fragments in 3 children after a significant amount of time had elapsed
      since the time of embolization. The embolized catheter and guide wire fragments
      were removed without any complications. We also describe the techniques used for
      their removal, and the problems encountered during the removal of these "old"
      foreign bodies.

PMID- 9637448
TI  - Vascular entrapment of a ruptured intra-aortic balloon: a case report of
      successful removal without surgery.
AB  - Intra-aortic balloon pump entrapment is a rare complication that may necessitate
      major abdominal surgery that is potentially life threatening in the critically
      ill patients who require balloon counterpulsation. We report successful removal
      of a ruptured and entrapped intra-aortic balloon pump catheter after use of
      streptokinase solution to clear clots from the device. We suggest this procedure
      as a safer, nonsurgical method that may eliminate the need for abdominal surgery.

PMID- 9637449
TI  - Fracture of coronary guidewire during rotational atherectomy with coronary
      perforation and tamponade.
AB  - We present the case of a calcified right coronary artery lesion with a 90-degree
      exit angle. Attempts at rotational atherectomy led to wire transection and vessel
      wall perforation necessitating emergent pericardiocentesis and bypass surgery. We
      review the literature on complications of rotational atherectomy and the
      management of coronary perforations and retained guidewire fragments.

PMID- 9637450
TI  - Successful retrieval of a lost coronary stent from the descending aorta using a
      loop basket intravascular retriever set.
AB  - Delivery of a balloon-expandable stent was complicated by a systemic
      embolisation. The radio-opaque stent was lost in the descending aorta, but then
      removed by using a loop basket intravascular retriever set without any peripheral
      arterial complication.

PMID- 9637451
TI  - Hemodynamic rounds series II: pulmonic balloon valvuloplasty.

PMID- 9637452
TI  - Laser wire for crossing chronic total occlusions: "learning phase" results from
      the U.S. TOTAL trial. Total Occlusion Trial With Angioplasty by Using a Laser
      Wire.
AB  - The Prima laser guidewire system (Spectranectics Corp., Colorado Springs, CO)
      consists of an 0.018" hypotube containing a bundle of 45-microm optical fibers
      coupled to a pulsed excimer laser operating at a tip fluence of 60 ml/mm2 and a
      repetition rate ranging from 25-40 Hz. This laser guidewire was specifically
      designed to cross total occlusions refractory to passage with conventional wires.
      The Prima wire was evaluated in a feasibility study at 15 U.S. centers. Following
      failure to cross a total occlusion with approved guidewires, the Prima wire was
      utilized in 179 patients. Average age of subjects was 61 yr. Lesion locations
      included left anterior descending (36%), right (45%), and circumflex (19%)
      coronary arteries. Mean angiographic age of total occlusions was 70 wk (range, 2
      1,020 wk, median, 14 wk). The use of the Prima wire either solely or in
      combination with conventional guidewires resulted in successful crossing in 61%
      of these previously impenetrable occlusions. Failure of the device was commonly
      related to length of the occlusion and tortuosity along the occluded pathway.
      Major complications included myocardial infarction in 7 patients (3.9%),
      tamponade in 3 (1.7%), and death in 2 (1.1%). This "learning phase" pilot study
      confirmed the feasibility of a laser guidewire in chronic total occlusions that
      are resistant to passage of conventional guidewires. An extended registry at
      these investigative sites is planned.

PMID- 9637453
TI  - Novel guide catheter for left coronary intervention via a right upper limb
      approach.
AB  - We designed a novel guide catheter specifically for interventions to the left
      coronary artery via a right upper limb approach. The catheter has a novel first
      loop design which utilizes the angle between the right subclavian and innominate
      arteries for support. The first loop introduces the catheter into the correct
      position and generates powerful and coaxial back-up power. We report successful
      implantation of Palmaz-Schatz stents in five cases using this 6 Fr. catheter.

PMID- 9637454
TI  - Inoue balloon for dilatation of aortic stenosis.

PMID- 9637455
TI  - Partial portacaval shunt for variceal hemorrhage: longitudinal analysis of
      effectiveness.
AB  - OBJECTIVE: To determine rates of survival, long-term patency, and recurrent
      variceal hemorrhage among patients with alcoholic cirrhosis treated by partial
      portacaval shunt. DESIGN: Single-institution cohort follow-up study of 72
      consecutive patients who underwent small-diameter portacaval H-graft shunt with
      collateral ablation during a 10-year period (1981 through 1990). Subjects were
      enrolled and followed up for up to 15 years. Shunt patency was assessed by
      portography and/or ultrasonography. We performed 7-year Kaplan-Meier analyses of
      survival (in 65 patients in Child classes A and B), shunt patency, and absence of
      variceal bleeding. SETTING: Tertiary academic referral center of the US
      Department of Veterans Affairs. PATIENTS: Patients with alcoholic cirrhosis were
      considered for operation after at least 1 proven episode of variceal hemorrhage.
      Patients with portal vein thrombosis were excluded; patients in Child class C
      underwent operation only for compelling indications. Of the 72 who underwent
      partial shunting, 38 were in Child class A, 27 were in class B, and 7 were in
      class C. INTERVENTIONS: Partial portacaval shunt (6-, 8- or 10-mm
      polytetrafluoroethylene H-graft with collateral ablation) and serial follow-up.
      MAIN OUTCOME MEASURES: Study end points were death, recurrent variceal
      hemorrhage, and unavailability for follow-up. Other measures included graft
      patency and nonvariceal rebleeding. RESULTS: Cumulative probability of 7-year
      patency for grafts at risk was 95%. The 7-year probability for absence of
      variceal bleeding in patients at risk was 92%. In 65 patients in Child classes A
      and B, operative mortality was 7.7% and the cumulative probability of 7-year
      survival was 54%. CONCLUSION: For variceal bleeding associated with alcoholic
      cirrhosis, the small-diameter polytetrafluoroethylene portacaval H-graft with
      collateral ablation affords durable patency and protection against variceal
      rebleeding.

PMID- 9637456
TI  - Transanal endoscopic microsurgery: a single surgeon's experience.
AB  - OBJECTIVE: To evaluate a single surgeon's experience with transanal endoscopic
      microsurgery (TEM) with regard to incidence of complications, recurrence rate of
      benign and malignant lesions, and impact on the treatment of rectal cancer.
      DESIGN: Prospective tumor registry. SETTING: Tertiary care university hospital.
      PATIENTS: Seventy-three patients undergoing TEM between January 1991 and November
      1996. MAIN OUTCOME MEASURES: Complications, recurrence rates, and use of this
      technique with respect to radical operations. RESULTS: The arrival of TEM was
      associated with an increase in the number of operations for rectal cancer;
      however, the use of TEM remained constant relative to radical resections. Use of
      TEM resection alone is appropriate for all adenomas and cancers staged Tis and
      T1. Use of TEM alone is not an appropriate treatment for T2 cancers. Four
      patients (5%) experienced fecal soilage, which was long lasting in only 1 (1%).
      CONCLUSIONS: Transanal endoscopic microsurgery is a safe technique and provides
      improved access to lesions in the middle and upper rectum. Thus far, it has not
      had a significant impact in the overall treatment of rectal cancer.

PMID- 9637457
TI  - An analysis of operations for gastroesophageal reflux disease: identifying the
      important technical elements.
AB  - BACKGROUND: Better understanding of the pathogenesis of gastroesophageal reflux
      disease in recent years has not been accompanied by appreciable advances in the
      design of antireflux operations. In many cases, operations are still being
      performed just as they were described 30 years ago. It is important now to go
      beyond the eponymous procedures traditionally associated with antireflux
      operations and to identify the technical elements that contribute to effective
      and durable fundoplications. OBJECTIVES: To compare antireflux operations and
      identify the important technical elements. DESIGN AND SETTING: Retrospective
      study in a university-based tertiary care center. PATIENTS: Two hundred one
      patients had laparoscopic fundoplications for gastroesophageal reflux disease.
      The first 22 patients underwent Nissen-Rossetti procedures (360 degree wrap; no
      division of short gastric vessels). Subsequently, 82 patients had a total (360
      degree Nissen wrap) fundoplication and 97 patients had a partial (240 degree
      Guarner wrap) fundoplication (both with the short gastric vessels divided), with
      the choice between them based on the quality of esophageal peristalsis. The 3
      groups of patients were similar in age, duration of symptoms, incidence of hiatal
      hernia, and incidence of esophagitis. MAIN OUTCOME MEASURES: Resolution of
      heartburn, incidence of postoperative dysphagia, and stability of the
      reconstruction. RESULTS: The resolution of heartburn was achieved for 15 patients
      (68%) who had the Nissen-Rossetti procedure, 73 patients (89%) who had a 360
      degrees Nissen wrap, and 88 patients (91%) who had a 240 degree Guarner wrap.
      Postoperative dysphagia occurred in 3 patients (14%) having the Nissen-Rossetti
      procedure, 5 patients (6%) having a 360 degree wrap, and 2 patients (2%) having a
      240 degree wrap. Herniation or disruption of the wrap occurred postoperatively in
      9 patients (4.5%). Review of the videotapes of these 9 operations showed that
      important technical elements had been omitted in 8. Seven patients required a
      second operation. CONCLUSION: Laparoscopic antireflux operations control symptoms
      without producing adverse effects if the following technical elements are
      included: the hernia is repaired and the hiatus reduced to a normal size, the
      short gastric vessels are divided, a total or partial wrap is used based on the
      quality of esophageal peristalsis, and the wrap is anchored in the abdomen.

PMID- 9637458
TI  - Total mesenteric excision in the surgical treatment of rectal cancer: a
      prospective study.
AB  - BACKGROUND: Total mesorectal excision has been advocated in conjunction with low
      anterior or abdominoperineal resection as the optimal surgical treatment for
      rectal cancer. It involves removal of the entire rectal mesentery as an intact
      unit and maximizes the likelihood of obtaining a negative circumferential margin.
      OBJECTIVES: To prospectively validate the efficacy of total mesorectal excision
      in obtaining locoregional control, to identify the perioperative factors
      influencing the selection of either a sphincter sparing or a sphincter ablating
      procedure, and to identify independent factors that may influence long-term
      prognosis in rectal cancers. SETTINGS: Tertiary referral center. PATIENTS:
      Seventy-three consecutive patients with rectal cancer located within 10 cm of the
      anal verge were treated from 1984 to 1997 by the senior author (F.M.). Sixty-five
      patients form the basis of our analysis after the exclusion of 7 patients who had
      their cancer removed transanally and 1 patient who had a permanent diverting
      stoma as the only procedure. RESULTS: Twenty-six patients underwent a sphincter
      ablating procedure; 39 underwent a sphincter sparing procedure. Operative
      mortality was 1.5%. Follow-up was complete in 64 patients (39+/-30 months; range,
      3-126 months). Five-year actuarial survival rates were 88% for the 34 patients
      with stage I and II adenocarcinoma and 65% for the 22 patients with stage III
      adenocarcinoma. The local recurrence rate was 6.2% overall, but only 3.1% in the
      potentially curable group (stages I-III). When only patients who did not receive
      adjuvant chemoradiation therapy were considered (n=23), local recurrence rate was
      8.3% overall and 0% in the potentially curable group. Tumor stage (P=.04) and
      vascular and/or lymphatic invasion (P=.002) were statistically significant in
      their association with survival. Circumferential lesions (P<.001), gross invasion
      of contiguous organs (P<.001) and distance from the anal verge of less than 5 cm
      (P=.01) were statistically significant in their association with the choice of a
      sphincter ablating procedure. CONCLUSIONS: This study confirms the efficacy of
      total mesorectal excision in minimizing locoregional recurrence rates and
      confirms the well-established prognostic value of stage and microinvasion.
      Moreover, it indicates that circumferential lesions, distance from anal verge,
      and gross invasion of contiguous organs are significant perioperative factors in
      the selection of the type of surgical procedure.

PMID- 9637459
TI  - Assessing outcomes, costs, and benefits of emerging technology for minimally
      invasive saphenous vein in situ distal arterial bypasses.
AB  - BACKGROUND: Instrumentation for a minimally invasive angioscopic in situ
      peripheral arterial bypass (MIAB) with catheter-directed side-branch occlusion
      has recently been approved for use. Despite the attractiveness of this approach
      (2 short incisions), benefits such as lower morbidity and shorter
      hospitalizations remain undocumented. To justify wide acceptance, minimally
      invasive surgical techniques must match conventional procedures in durability and
      cost while enhancing patient comfort. Often such comparisons are difficult during
      the implementation phase of a new procedure. OBJECTIVE: To compare the outcomes
      of the MIAB procedures with a concurrent group of patients undergoing
      conventional in situ bypass procedures. DESIGN: Retrospective review. SETTING:
      University medical center. PATIENT: The first 20 consecutive MIAB procedures in
      19 patients performed between August 1, 1995, and July 31, 1997, were compared
      with 19 contemporaneous consecutive conventional in situ bypass procedures
      performed at the same institution. MAIN OUTCOME MEASURES: Operative time,
      postoperative length of stay, hospital costs, complications, primary assisted and
      secondary patency, limb salvage, and survival. RESULTS: The patient groups were
      comparable with respect to age, sex, incidence of smoking, coronary artery
      disease, hypertension, diabetes, renal failure, cerebrovascular disease,
      indication, and distal anastomosis level. The median operative time was
      significantly greater for the MIAB group (6.6 hours vs 5.7 hours; P=.009), and
      intraoperative completion arteriography more frequently showed retained
      arteriovenous fistulas in the MIAB group (55% vs 21%; P=.05). The median
      postoperative length of stay and total cost were 6.5 days and $18,000 for the
      MIAB group and 8 days and $27,800 for the conventional group (P > or = .05).
      There were no significant differences in major complications (10% in the MIAB
      group vs 11% in the conventional group), wound complications (10% vs 11%,
      respectively), primary assisted patency at 1 year (68%+/-11% vs 78%+/-10%,
      respectively), secondary patency at 1 year (79%+/-10% vs 88%+/-8%, respectively),
      limb salvage at 1 year (85%+/-10% vs 94%+/-6%, respectively), or patient survival
      at 1 year (89%+/-8% vs 61%+/-13%, respectively). CONCLUSION: Patients undergoing
      the MIAB procedure avoided lengthy vein exposure incisions without sacrificing
      short-term results. There was a trend toward decreased hospital stay and cost,
      which may be further realized as the clinical experience broadens. Although
      longer follow-up and larger cohorts will always be required to define durability,
      immediate access to outcomes and costs on small numbers of patients facilitates
      the early assessment of emerging technology.

PMID- 9637460
TI  - Delayed complications of nonoperative management of blunt adult splenic trauma.
AB  - OBJECTIVE: To determine the incidence and type of delayed complications from
      nonoperative management of adult splenic injury. DESIGN: Retrospective medical
      record review. SETTING: University teaching hospital, level I trauma center.
      PATIENTS: Two hundred eighty patients were admitted to the adult trauma service
      with blunt splenic injury during a 4-year period. Men constituted 66% of the
      population. The mean (+/-SEM) age was 32.2+/-1.0 years and the mean (+/-SEM)
      Injury Severity Score was 22.8+/-0.9. Fifty-nine patients (21%) died of multiple
      injuries within 48 hours and were eliminated from the study. One hundred thirty
      four patients (48%) were treated operatively within the first 48 hours after
      injury and 87 patients (31%) were managed nonoperatively. MAIN OUTCOME MEASURES:
      We reviewed the number of units of blood transfused, intensive care unit length
      of stay, overall length of stay, outcome, and complications occurring more than
      48 hours after injury directly attributable to the splenic injury. RESULTS:
      Patients managed nonoperatively had a significantly lower Injury Severity Score
      (P<.05) than patients treated operatively. Length of stay was significantly
      decreased in both the number of intensive care unit days as well as total length
      of stay (P<.05). The number of units of blood transfused was also significantly
      decreased in patients managed nonoperatively (P<.05). Seven patients (8%) managed
      nonoperatively developed delayed complications requiring intervention. Five
      patients had overt bleeding that occurred at 4 days (3 patients), 6 days (1
      patient), and 8 days (1 patient) after injury. Three patients underwent
      splenectomy, 1 had a splenic artery pseudoaneurysm embolization, and 1 had 2
      areas of bleeding embolization. Two patients developed splenic abscesses at
      approximately 1 month after injury; both were treated by splenectomy. CONCLUSION:
      Significant numbers of delayed splenic complications do occur with nonoperative
      management of splenic injuries and are potentially life-threatening.

PMID- 9637461
TI  - CD4 cell counts as a prognostic factor of major abdominal surgery in patients
      infected with the human immunodeficiency virus.
AB  - OBJECTIVE: To measure the prognostic utility of helper T-cell (CD4) counts in
      human immunodeficiency virus (HIV)-infected patients undergoing major abdominal
      surgery. DESIGN: Retrospective case series. SETTING: Three university-affiliated
      hospitals. PATIENTS: Forty-three HIV-infected patients undergoing major abdominal
      surgery. MAIN OUTCOME MEASURES: Morbidity and mortality rates with respect to CD4
      cell counts. RESULTS: Nineteen of 32 patients who had CD4 cell counts less than
      0.20 X 10(9)/L (200 cells/microL) suffered major complications compared with 2 of
      11 patients who had CD4 cell counts greater than 0.20 x 10(9)/L (200
      cells/microL) (P=.03). Perioperative mortality was 38% for patients with CD4 cell
      counts less than 0.20 x 10(9)/L, and was 9% for those with CD4 cell counts
      greater than 0.20 x 10(9)/L (P=.13). Six months postoperatively, mortality rates
      were 47% and 9%, respectively (P=.03). Of patients with septic processes
      perioperatively (n=12), mortality was 75%, and was 19% (P=.009) for those with
      nonseptic processes (n=31). Nine patients had HIV-related intra-abdominal
      pathologic conditions at laparotomy. Mortality was 56% perioperatively (P=.13)
      and 88% after 6 months (P=.001). Sixty-eight percent of patients who received
      blood product transfusions developed complications, whereas only 7% of those who
      did not receive transfusions developed complications (P<.001). Overall mortality
      and morbidity rates were 37% and 49%, respectively. Patients with morbidity had
      lower CD4 cell counts (median, 0.034 x 10(9)/L) than those without complications
      (median, 0.102 x 10(9)/L) (P=.02). Similarly, patients who died had lower CD4
      cell counts (median, 0.031 x 10(9)/L vs 0.088 x 10(9)/L) (P=.05). CONCLUSIONS:
      Patients with acquired immunodeficiency syndrome-defining CD4 cell counts
      undergoing major abdominal surgery developed more complications and had poorer
      outcomes at 6-month follow-up compared with HIV-infected patients whose CD4 cell
      counts were greater than 0.20 x 10(9)/L (200 cells/microL). A perioperative
      septic process and HIV-related pathologic conditions seen at laparotomy are also
      associated with worse outcomes.

PMID- 9637462
TI  - Intra-aortic balloon counterpulsation in patients with severe cardiac dysfunction
      undergoing abdominal operations.
AB  - OBJECTIVE: To assess the effectiveness of intra-aortic balloon counterpulsation
      (IABC) as adjunctive treatment in patients undergoing abdominal operations.
      DESIGN: Retrospective review of patient medical records to determine the
      incidence of mortality following abdominal surgery and the incidence of
      complications from IABC. SETTING: University-based, tertiary care hospital.
      PATIENTS: Sixty-eight patients who underwent an abdominal operation and IABC
      during the same hospitalization were divided into the following groups: Group 1,
      IABC initiated prior to operation to enhance perioperative cardiac function;
      group 2, IABC used to treat cardiogenic shock in a patient who subsequently
      required an operation while undergoing IABC; and group 3, IABC device inserted
      and removed for treatment of cardiogenic shock in a patient who subsequently
      required an operation within 30 days of removal of the device. MAIN OUTCOME
      MEASURES: The incidence of mortality in IABC-supported patients and IABC-related
      complications. RESULTS: In group 1, excluding 3 patients who died following
      emergency operation, 26 patients underwent nonemergency procedures and had a 12%
      mortality rate. In group 2, 5 of 6 patients who underwent emergency operations
      died, whereas 3 of 4 patients who required only urgent operations survived. In
      group 3, 18 (62%) of 29 patients who underwent urgent or emergent operations died
      postoperatively. Thirteen patients experienced complications related to IABC;
      there were no deaths and no limbs were lost to ischemia. CONCLUSIONS: This is the
      largest reported series looking at the utility of IABC as adjunctive treatment
      for patients undergoing abdominal operations. The outcome for those patients
      requiring emergency operations remains poor, but it is likely that more liberal
      use of IABC in patients with severe cardiac dysfunction who require nonemergency
      operations may improve patient outcome.

PMID- 9637464
TI  - Treatment strategy for patients with cystic lesions mimicking a liver tumor: a
      recent 10-year surgical experience in Japan.
AB  - OBJECTIVE: To clarify some of the difficulties in determining the appropriate
      surgical indications for cystic lesions mimicking a neoplasm in the liver.
      DESIGN: A retrospective review of hepatic resections for cystic lesions mimicking
      a neoplasm in the liver between August 1, 1986, and July 31, 1996. SETTING: A
      university hospital with a long history of hepatic resection for cystic lesions
      mimicking a neoplasm in the liver. PATIENTS: Ten patients with such cystic
      lesions in the liver, who underwent a hepatectomy during a recent 10-year period,
      were included in this study. MAIN OUTCOME MEASURES: Detailed clinicopathologic
      data were analyzed, and comparisons were made between the preoperative and
      postoperative diagnoses. RESULTS: The postoperative diagnoses consisted of cysts,
      including cysts complicated by an infection or hemorrhage in 7 patients,
      localized cystic dilation of the bile duct due to hepatolithiasis in 1,
      cystadenoma in 1, and mucin-producing cholangiocarcinoma in 1. In only one case
      was postoperative diagnosis identical to the preoperative diagnosis. In one case,
      an intraoperative pathological examination showed the tumor to be a mucin
      producing cholangiocarcinoma instead of a cystadenocarcinoma. A tumor-marker
      analysis of the fluid in the cystic lesions also did not contribute to a definite
      diagnosis. Furthermore, cytological examination of the fluid could not completely
      exclude malignancy. Neither mortality nor morbidity occurred in any of the
      patients, and their mean length of hospitalization after hepatectomy was only
      13.7 days. CONCLUSIONS: The accurate diagnosis of cystic lesions mimicking a
      tumor remains problematic; however, the results of hepatectomy for such cases are
      normally satisfactory. Such cystic lesions of the liver should be indicated for
      hepatectomy whenever the possibility of a cancerous neoplasm cannot be completely
      ruled out.

PMID- 9637463
TI  - Video-assisted thoracic surgery in the treatment of posttraumatic empyema.
AB  - BACKGROUND: Video-assisted thoracic surgery (VATS) appears to be replacing open
      thoracotomy for the treatment of posttraumatic thoracic complications. OBJECTIVE:
      To compare operative times, complication rates, and outcomes in patients who
      underwent VATS vs open thoracotomy. DESIGN: Retrospective review. SETTING:
      University hospital, level I trauma center. PATIENTS: Trauma patients who between
      December 1993 and May 1997 underwent open thoracotomy or VATS to drain a
      persistent thoracic collection. METHODS: Medical records were reviewed for
      demographic data, operative times, and clinical outcomes. RESULTS: Of the 524
      trauma patients requiring tube thoracostomy, 22 underwent 23 procedures to drain
      empyema (17 VATS, 6 thoracotomies [based on surgeon preferencel). There were no
      differences in age, Injury Severity Score, or mechanism of injury between the 2
      groups. Three patients who underwent VATS (18%) required conversion to open
      thoracotomy for adequate drainage. All remaining patients who underwent VATS had
      successful treatment of their empyema. Complication rates (VATS=29%, open
      thoracotomy=33%; P=.99), operative times (VATS=3.4+/-1.3 hours [mean+/-SD], open
      thoracotomy=3.0+/-1.5 hours; P=.46), postoperative epidural catheter use
      (VATS=31%, open thoracotomy=50%; P=.63), duration of chest tube drainage
      (VATS=5.1+/-1.7 days [mean+/-SD], open thoracotomy=4.5+/-1.5 days; P=.48), and
      hospital stay after the procedure (VATS=16+/-14 days [mean+/-SD], open
      thoracotomy=11+/-5 days; P=.39) were similar for both groups. CONCLUSIONS: Video
      assisted thoracic surgery was a safe and effective operative strategy for the
      treatment of posttraumatic empyema. Therefore, because VATS has been shown in
      nontrauma patients to reduce morbidity and because it provides better cosmesis,
      we believe that it should be the initial operative approach to trauma patients
      with suspected posttraumatic empyema.

PMID- 9637465
TI  - Therapeutic effect of sentinel lymphadenectomy in T1 breast cancer.
AB  - OBJECTIVE: To evaluate whether the tumor status of the sentinel lymph node (SN)
      would alter the systemic adjuvant therapy administered to patients with T1 breast
      cancer. DESIGN AND PATIENTS: Consecutive breast cancer patients (tumors < or = 2
      cm) who underwent successful sentinel lymphadenectomy. MAIN OUTCOME MEASURES:
      Metastatic tumor in the SN, primary tumor size, recommendations for systemic
      adjuvant therapy before and after histopathologic evaluation of the SN, and
      actual systemic adjuvant therapy received by the patient. RESULTS: Of 142 total
      patients, 14 had T1a tumors; 35, T1b; and 93, T1c. Recommendations for systemic
      adjuvant therapy were initially determined solely by primary tumor
      characteristics and menopausal status. These recommendations were compared with
      recommendations for systemic adjuvant therapy based on tumor characteristics,
      menopausal status, and SN status; and then were compared with actual systemic
      adjuvant therapy received by the patient. Among the 118 patients with T1a, T1b,
      and favorable (positive estrogen or progesterone receptors and a low S-phase
      percentage with respect to DNA content) T1c tumors, 15 (37.5%) of 40
      premenopausal patients and 20 (25.6%) of 78 postmenopausal patients became
      candidates for chemotherapy when examination of the SN revealed axillary
      metastasis; chemotherapy was actually administered to all 15 premenopausal
      patients but to only 6 postmenopausal patients. In the remaining 24 patients with
      unfavorable T1c tumors, SN status did not change the recommendation for
      chemotherapy but may have altered the choice of specific chemotherapeutic agents.
      CONCLUSIONS: Identification of tumor-involved SN may alter systemic adjuvant
      therapy in patients with T1a, T1b, and favorable T1c tumors and may potentially
      change the type or dose of chemotherapeutic agents given to patients with
      unfavorable T1c tumors. Surgical axillary staging of the axilla remains an
      essential part of breast cancer management and should not be abandoned.

PMID- 9637466
TI  - Effects of carbon dioxide pneumoperitoneum, air pneumoperitoneum, and gasless
      laparoscopy on body weight and tumor growth.
AB  - BACKGROUND: The oncologic consequences of intraperitoneal carbon dioxide (CO2)
      insufflation during the laparoscopic resection of cancer are under debate. The
      effect of other insufflating gases or gasless laparoscopy on cancer requires
      study. OBJECTIVE: To study body weight and tumor growth in rats after CO2
      pneumoperitoneum, air pneumoperitoneum, and gasless laparoscopy. METHODS: On day
      1, an 8-mg bolus of ROS-1 tumor was placed under the renal capsule of both
      kidneys in rats. In experiment A, rats had either CO2 insufflation (n=10) or a
      gasless laparoscopic bowel resection (n=10) on day 3 and were humanely killed
      after 7 days. In experiment B, rats had either a laparoscopic bowel resection
      with CO2 insufflation (n=11) or insufflation with air (n=11) on day 3 and were
      killed after 7 days. In both experiments, postoperative weight loss and tumor
      growth were measured, and the differences were tested with an analysis of
      covariance. RESULTS: Renal subcapsular tumor growth in the group having gasless
      laparoscopy was less than that in the group having CO2 pneumoperitoneum (P=.04).
      Postoperative weight loss in these groups showed no differences (P=.55). No
      differences in tumor growth or weight loss were found between rats having
      insufflation with CO2 and those having insufflation with air (P=.61 and P=.68,
      respectively). CONCLUSIONS: The restoration of body weight after a laparoscopic
      surgical procedure was similar with CO2, air, or gasless laparoscopy. Gasless
      laparoscopy was associated with less renal subcapsular tumor growth than was
      insufflation with CO2. Therefore, the application of gasless techniques in
      laparoscopic oncologic surgical treatment demands further study.

PMID- 9637467
TI  - Objective evaluation of a laparoscopic surgical skill program for residents and
      senior surgeons.
AB  - BACKGROUND: Laparoscopic surgery adapts poorly to apprenticeship models for
      general surgical training. Standardized skill acquisition and validation
      programs, targeted performance goals, and a supervised, enforced, skill-based
      curriculum that readily can be shared between trainee and instructor must replace
      the observation and incremental skill-acquisition model used in an open surgical
      environment. The Yale Laparoscopic Skills and Suturing Program was used to
      develop a data bank for objective evaluation of dexterity and suturing skills for
      laparoscopic surgical training. The current study compares trainee and senior
      surgeon performance in this standardized training program. OBJECTIVE: To compare
      objectively evaluated laparoscopic surgical skills and suturing capability of
      senior surgeons and of residents after they have completed the same standardized
      training regimen. METHODS: Two hundred ninety-one trained surgeons performed 8730
      standardized laparoscopic dexterity drills and 2910 intracorporeal suturing
      exercises in the Yale Laparoscopic Skills and Suturing Program. Their performance
      was supervised by an instructor who recorded performance and timing of the tasks
      in a 2 1/2-day program. Ninety-nine residents performed the same drills and
      exercises the same number of times and followed the same technique for
      intracorporeal suturing. Percentile graphs were prepared for each type of drill
      and suturing exercise to allow comparison of levels of achievement among
      different training groups. RESULTS: The performance of the residents was the same
      as that of trained surgeons for the rope pass drill and the suturing exercise.
      Residents in comparison with trained surgeons performed the triangle transfer
      drill faster and the new cup drop drill and old cup drop drill more slowly. There
      was no significant difference in performance between male and female residents.
      CONCLUSION: Basic skills relevant to laparoscopic performance can be acquired
      with a high level of competence in a brief course unrelated to prior surgical
      experience, sex, or age.

PMID- 9637468
TI  - Diagnostic delay in breast disease: a system analysis of a public urban hospital.
AB  - OBJECTIVE: To analyze the diagnostic process in 146 women referred to a breast
      clinic in an urban setting between January 1, 1994, and December 31, 1996.
      DESIGN: We devised the "diagnostic delay index (DDI)," defined as the time
      between the medical system's awareness of a diagnostic need and the completion of
      the diagnostic process. The time awaiting breast clinic consultation and the
      diagnostic events experienced--including clinic visits, imaging studies, and
      biopsies--were recorded. We stratified patients in 2 pathways (palpable masses
      and mammogram-identified lesions) and by benign or malignant outcome. RESULTS:
      Patients in pathways 1 (n = 85) and 2 (n=61) had a mean (+/-SD) DDI of 68.4 (+/
      46.9) days and 71.9 (+/-35.2) days, respectively. Patients in both pathways who
      had a malignant outcome had a significantly lower DDI than those who had a benign
      outcome (47.5+/-30.9 days vs 78.6+/-42.6) (P<.001); this advantage was most
      pronounced in patients with palpable lumps. The average patient waited more than
      3 weeks for both an initial clinic consultation and operating room access.
      Quartile analysis of the DDI revealed statistically significant differences in
      clinic access time, number of visits, diagnostic events per visit, and operating
      room access time. Regression analysis demonstrates the relationship between DDI
      and measured process variables: DDI= -21.11+0.09 age+1.86 pathway-12.18
      outcome+1.08 clinic access+11.91 visits+0.94 operating room access (R2=61.5%).
      CONCLUSIONS: In a public hospital, diagnostic delay is related to inadequate
      access to surgical consultation and a delay in operating room access. Regression
      analysis demonstrates the relationships between these components of system
      diagnostic delay and suggests strategies for reducing the DDI.

PMID- 9637470
TI  - Spigelian hernias: a new repair technique using preshaped polypropylene umbrella
      plugs.
AB  - The spigelian hernia is a rare kind of abdominal wall defect that has been
      treated using a variety of techniques. Recently, we encountered 6 patients with
      spigelian hernias in whom we have used a new modality consisting of the tension
      free occlusion of the hernia ring with a preshaped polypropylene umbrella-type
      plug. The follow-up was more than 1 year without evidence of recurrence. This
      technique simplifies the repair and has the advantage of producing minimal
      postoperative pain and disability.

PMID- 9637469
TI  - Genes don't count.
AB  - It is the regulation of gene expression that determines phenotype and cellular
      response. Several families of proteins control gene expression in cells and
      influence the pathogenesis of multiple organ failure, the acute phase response,
      atherosclerosis, and graft-vs-host disease. Understanding the basics of the
      regulation of gene transcription will allow the knowledgeable surgeon to target
      gene expression as a therapeutic modality in multiple diseases. We examine
      nuclear factor kappa B as an example of a transcription factor that is involved
      in multiple surgical diseases and has pharmacological inhibitors available to
      knowledgeable surgeons.

PMID- 9637471
TI  - Osteitis fibrosa cystica with renal parathyroid hormone resistance: a review of
      pseudohypoparathyroidism with insight into calcium homeostasis.
AB  - Pseudohypoparathyroidism is a group of diseases characterized by renal resistance
      to parathyroid hormone. The patients typically have the bony manifestations of
      hyperparathyroidism, while being hypocalcemic. Pseudohypoparathyroidism has
      further been subdivided into types Ia, Ib, Ic, and II. Mutations involving any
      number of domains of the parathyroid hormone receptor, adenylate cyclase, or G
      proteins may alter the cellular response to parathyroid hormone. This wide range
      of possible sites of mutation may explain the heterogeneous biochemical,
      skeletal, and physical phenotypes associated with the various types of
      pseudohypoparathyroidism. We describe a patient with pseudohypoparathyroidism who
      was successfully treated with total parathyroidectomy and gland
      autotransplantation. The complexities of parathyroid hormone cellular
      interactions and calcium homeostasis are discussed. Pseudohypoparathroidism is an
      unusual disease; however, it provides an elegant model for studying problems of
      calcium balance.

PMID- 9637472
TI  - RET proto-oncogene mutation analysis for multiple endocrine neoplasia, type 2.

PMID- 9637473
TI  - Problems of total parenteral nutrition.

PMID- 9637474
TI  - When giants walked the land.

PMID- 9637475
TI  - Eiloides of the neck in a negro girl.

PMID- 9637476
TI  - Cutting edge: role of macrophage migration inhibitory factor in inhibiting NK
      cell activity and preserving immune privilege.
AB  - The absence of MHC class I Ags on the corneal endothelium, which lines the
      anterior chamber of the eye, makes this cell layer potentially vulnerable to
      lysis by NK cells. However, aqueous humor (AH), which bathes the corneal
      endothelium, contains a 12-kDa protein which inhibits the NK-mediated lysis of
      corneal endothelial cells. An amino acid sequence analysis of AH revealed that
      this factor shared >90% homology with macrophage migration inhibitory factor
      (MIF). The NK inhibitory effect of AH was neutralized with anti-human MIF Ab.
      Moreover, mouse rMIF produced a similar inhibition of NK cell activity. However,
      neither rMIF nor AH inhibited the CTL-mediated Lysis of allogeneic cells. rMIF
      prevented the release of perforin granules by NK cells but not CTLs. Although MIF
      displays proinflammatory properties, these results indicate that it can also
      inhibit at least one immune effector element, NK cells, and thereby contribute to
      immune privilege in the eye.

PMID- 9637477
TI  - Cutting edge: JAK3 activation and rescue of T cells from HIV gp120-induced
      unresponsiveness.
AB  - In early HIV disease, immunodeficiency is characterized by the inability of CD4+
      T cells to produce a critical cytokine, IL-2, and to express the receptor for IL
      2 (IL-2R) in response to antigenic or mitogenic stimulation. The shared common
      gamma-chain (gamma(c)) of IL-2R and its associated Janus kinase, JAK3, are
      indispensable for normal T cell function. Here, we show that the inhibition of IL
      2R expression and proliferation induced by ligation of CD4 by HIV envelope
      glycoprotein, gp120, is correlated with inhibition of expression and activation
      of JAK3. Stimulation through the gamma(c)-related cytokine receptors restores
      JAK3 expression and activation and rescues CD4-mediated T cell unresponsiveness.
      Collectively, these data argue that inhibition of JAK3 expression and activation
      may, in part, explain the T cell dysfunction seen in early HIV disease. In
      addition, rescue from gp120-mediated T cell unresponsiveness by activation of
      JAK3 suggests a novel therapeutic approach for enhancing immune function in HIV
      disease.

PMID- 9637478
TI  - Cutting edge: antigen-dependent regulation of telomerase activity in murine T
      cells.
AB  - Telomeres, structures on the ends of linear chromosomes, function to maintain
      chromosomal integrity. Telomere shortening occurs with cell division and provides
      a mechanism for limiting the replicative potential of normal human somatic cells.
      Telomerase, a ribonucleoprotein enzyme, synthesizes telomeric repeats on
      chromosomal termini, potentially extending the capacity for cell division. The
      present study demonstrates that resting T cells express little/no activity, and
      optimal Ag-specific induction of telomerase activity in vitro requires both TCR
      and CD28-B7 costimulatory signals. Regulation of telomerase in T cells during in
      vivo Ag-dependent activation was also assessed by adoptive transfer of TCR
      transgenic T cells and subsequent Ag challenge. Under these conditions,
      telomerase was induced in transgenic T cells coincident with a phase of extensive
      clonal expansion. These findings suggest that telomerase may represent an
      adoptive response that functions to preserve replicative potential in Ag-reactive
      lymphocytes.

PMID- 9637479
TI  - Specific immune induction following DNA-based immunization through in vivo
      transfection and activation of macrophages/antigen-presenting cells.
AB  - The initiation of an adaptive immune response requires Ag presentation in
      combination with the appropriate activation signals. Classically, Ag presentation
      and immune activation occur in the lymph node and spleen, where a favorable organ
      architecture and rich cellular help can enhance the process. Recently, several
      investigators have reported the use of DNA expression cassettes to elicit
      cellular and humoral immunity against diverse pathogens. Although the immune
      mechanisms involved are still poorly understood, plasmid inoculation represents a
      model system for studying immune function in response to invading pathogens. In
      this report, we demonstrate the presence of activated macrophages or dendritic
      cells in the blood lymphocyte pool and peripheral tissues of animals inoculated
      with DNA expression cassettes. These cells are directly transfected in vivo,
      present Ag, and display the surface proteins CD80 and CD86. Our studies indicate
      that these cells function as APC and can activate naive T lymphocytes. They may
      represent an important first step APC in genetic immunization and natural
      infection.

PMID- 9637480
TI  - Factors involved in the differentiation of TGF-beta-producing cells from naive
      CD4+ T cells: IL-4 and IFN-gamma have opposing effects, while TGF-beta positively
      regulates its own production.
AB  - TGF-beta has been shown to play a central role in regulating inflammatory
      responses; thus, understanding the factors involved in the generation of TGF-beta
      producing cells could lead to interventions that are useful in effecting disease
      progression. In initial studies, the capacity of naive CD4+ T cells from TCR
      transgenic (Tg) mice to produce TGF-beta following primary and secondary
      stimulation was assessed. TGF-beta, IL-4, or IFN-gamma production could not be
      detected from highly purified naive CD4+/lymphocyte endothelial cell adhesion
      molecule (LECAM)-1high cells following primary stimulation for 36 h with plate
      bound anti-CD3, anti-CD28, and IL-2. This population was subsequently used to
      study the differentiation of TGF-beta-producing CD4+ T cells. In further studies,
      naive CD4+/LECAM-1high cells from TCR transgenic mice of both the BALB/c and
      B10.A backgrounds were stimulated with T-depleted spleen cells (TDS) and specific
      peptide in the presence of various cytokines and/or cytokine antagonists for 5
      days, restimulated, and TGF-beta, IL-4, and IFN-gamma production were measured.
      Priming conditions favoring high IL-4 production and/or low IFN-gamma production
      greatly enhanced TGF-beta production in secondary cultures. Furthermore, the
      presence of IL-10 in cultures was associated with an increase in TGF-beta
      production following restimulation. The importance of IL-4 and IFN-gamma in
      regulating TGF-beta production was confirmed in studies showing that cells from
      IFN-gamma(-/-) mice produced more TGF-beta, while cells from IL-4(-/-) mice
      produced less TGF-beta compared with wild-type controls. Finally, the addition of
      exogenous TGF-beta to priming cultures significantly enhanced the production of
      TGF-beta upon restimulation, demonstrating that TGF-beta has a role in self
      regulating its own production.

PMID- 9637481
TI  - Macrophage-derived nitric oxide regulates T cell activation via reversible
      disruption of the Jak3/STAT5 signaling pathway.
AB  - Nitric oxide (NO) has been invoked as an important pathogenic factor in a wide
      range of immunologically mediated diseases. The present study demonstrates that
      macrophage-derived NO may conversely function to fine tune T cell-mediated
      inflammation via reversible dephosphorylation of intracellular signaling
      molecules, which are involved in the control of T cell proliferation. Thus, T
      cells activated in the presence of alveolar macrophages are unable to proliferate
      despite expression of IL-2R and secretion of IL-2. This process is reproduced by
      the NO generator S-nitroso-N-acetylpenicillamine and is inhibitable by the NO
      synthase inhibitor N(G)-methyl-L-arginine. Analysis of T cell lysates by
      immunoprecipitation with specific Abs and subsequent immunoblotting indicated
      marked reduction of tyrosine phosphorylation of Jak3 and STAT5 mediated by NO.
      Further studies indicated that NO-mediated T cell suppression was reversible by
      the guanylate cyclase inhibitors methylene blue and LY-83583 and was reproduced
      by a cell-permeable analogue of cyclic GMP, implicating guanylate cyclase
      activation as a key step in the inhibition of T cell activation by NO.

PMID- 9637482
TI  - The trophic action of IL-7 on pro-T cells: inhibition of apoptosis of pro-T1, 
      T2, and -T3 cells correlates with Bcl-2 and Bax levels and is independent of Fas
      and p53 pathways.
AB  - Signals from the IL-7R are essential for normal thymocyte development. We
      isolated thymocytes from early developmental stages and observed that suspensions
      of pro-T1, -T2, and -T3 cells rapidly died in culture. Addition of IL-7 promoted
      their survival, but did not induce cell division. Pro-T4 cells did not undergo
      rapid cell death, and their survival was therefore independent of IL-7. Death in
      the absence of IL-7 showed the hallmarks of apoptosis, including DNA
      fragmentation and annexin V binding; however, caspase inhibitors blocked DNA
      fragmentation, but did not block cell death. The trophic effect of IL-7 was
      partially inhibited by blocking protein synthesis. The p53 pathway was not
      involved in this death pathway, since pro-T cells from p53-/- mice also underwent
      cell death in the absence of IL-7. The Fas/Fas ligand pathway was not involved in
      cell death, since Fas-deficient pro-T cells died normally in the absence of IL-7,
      anti-Fas Abs did not protect cells from death in the absence of IL-7, and Fas
      expression was undetectable on cells at these stages. The IL-7 trophic affect
      correlated with increased intracellular levels of Bcl-2 and decreased levels of
      Bax, whereas no Bcl-X(L), Bcl-w, or Bad was detectable. Thus, maintaining a
      favorable Bcl-2/Bax ratio may account for the trophic action of IL-7.

PMID- 9637484
TI  - Immunologic characterization of CD7-deficient mice.
AB  - Human CD7 is an Ig superfamily molecule that is expressed on mature T and NK
      lymphocytes. Although in vitro studies have suggested a role for CD7 in lymphoid
      development and function, the exact function of CD7 in vivo has remained elusive.
      One patient has been reported with SCID syndrome attributed to CD7 deficiency. To
      study in vivo functions of CD7, we have generated CD7-deficient mice and assessed
      their lymphoid development and function. CD7-deficient mice were viable, had
      normal peripheral blood and spleen lymphocyte numbers, and had normal specific Ab
      responses with Ag-driven Ig isotype switching. Thymocyte numbers were normal in 4
      wk-old, 6-mo-old, and 1-yr-old CD7-deficient mice, but in 3-mo-old CD7-deficient
      mice, total thymocyte numbers were significantly increased by 60% (p < 0.02)
      compared with normal age-matched +/+ littermates. CD7-deficient splenocytes
      proliferated normally in response to various mitogens, including PHA, anti-CD3,
      Con A, and LPS. While NK cell numbers and cytolytic activity to YAC targets were
      normal, CD7-deficient mice had lower Ag-induced MHC class I-restricted CTL
      activity against OVA-transfected target cells than did +/+ control mice. Thus,
      CD7-deficient mice did not have a SCID syndrome, but rather had transient
      increases in thymocyte numbers at age 3 mo and altered splenocyte Ag-specific CTL
      effecter cell activity. These data suggest a role for CD7 in regulating
      intrathymic T cell development and in mediating CTL effecter function.

PMID- 9637483
TI  - Targeting the IL-15 receptor with an antagonist IL-15 mutant/Fc gamma2a protein
      blocks delayed-type hypersensitivity.
AB  - Owing to shared receptor components, the biologic activities of IL-15 are similar
      to those of IL-2. However, the patterns of tissue expression of IL-2/IL-2R alpha
      and IL-15/IL-15R alpha differ. The development of agents targeting the receptor
      and signaling elements of IL-15 may provide a new perspective for treatment of
      diseases associated with expression of IL-15/IL-15R. We designed, genetically
      constructed, and expressed a receptor site-specific IL-15 antagonist by mutating
      glutamine residues within the C terminus of IL-15 to aspartic acid and
      genetically linked this mutant IL-15 to murine Fc gamma2a. These mutant IL-15
      proteins specifically bind to the IL-15R, competitively inhibit IL-15-triggered
      cell proliferation, and do not activate the STAT-signaling pathway. Because the
      receptor site-specific antagonist IL-15 mutant/Fc gamma2a fusion proteins had a
      prolonged t(1/2) in vivo and the potential for destruction of IL-15R+ leukocytes,
      we examined the immunosuppressive activity of this agent. An IL-15 mutant/Fc
      gamma2a fusion protein markedly attenuated Ag-specific delayed-type
      hypersensitivity responses and decreased leukocyte infiltration within the
      delayed-type hypersensitivity sites. These findings suggest that 1) IL-15/IL-15R+
      cells are crucial to these T cell-dependent immune responses, and 2) treatment
      with IL-15 mutant/Fc gamma2a protein may ameliorate T cell-dependent
      immune/inflammatory diseases.

PMID- 9637485
TI  - Antigen activation rescues recent thymic emigrants from programmed cell death in
      the BB rat.
AB  - One of the diabetes susceptibility genes of the BB rat is a mutation at the lyp
      locus that decreases the thymic output of T cells and the life span of most
      recent thymic emigrants (RTE). Consequently, there is a 10-fold reduction in the
      number of CD4+ and CD8+ T cells in secondary lymphoid organs. Results presented
      in this work demonstrate that the BB rat lyp mutation is associated with an
      accelerated apoptotic death in vitro of mature CD4+ 8- and CD4- 8+ thymocytes and
      peripheral T cells. The stability of the pool of recirculating T cells (PRL) of
      BB rats over time results from a > 10-fold increase in the mitotic activity of T
      cells as assessed in vivo by bromodeoxyuridine incorporation. This increased
      mitotic activity is not observed when BB T cells develop in the context of a
      normal sized PRL. MHC haploidentical WF and BB rats differ at minor
      histocompatibility loci. Intravenous injection of (WF x BB)F1 T cells into
      euthymic BB rats led to the rejection of donor T cells within 3 wk by unprimed
      recipients and within 1 wk by primed recipients. This secondary immune response
      was unaffected by postpriming thymectomy. F1 T cells were not rejected, but
      rather expanded after their injection into thymectomized BB rats that had been
      primed as early as 48 h after thymectomy. These results strongly suggest that the
      BB rat PRL is devoid of long-lived naive T cells and that rescue of recent thymic
      emigrants from programmed cell death is initiated by Ags, exclusively.

PMID- 9637486
TI  - Thymus requirement and antigen dependency in the "infectious" tolerance pathway
      in transplant recipients.
AB  - We have shown that features of infectious tolerance, as originally described in
      thymectomized mice, may be applied to euthymic rat recipients of heart
      transplants. We now report on studies aimed at exposing mechanisms underlying the
      infectious tolerance pathway, with emphasis on the role of thymus and
      alloantigen. Pretransplant thymectomy diminished the efficacy of CD4-targeted
      therapy, with donor-specific tolerance induced in approximately 50% of
      recipients. Thymus was required for generation of regulatory T cells under the
      cover of CD4 mAb therapy and for the ability of these cells to confer infectious
      tolerance. However, thymus was not mandatory to maintain an infectious-permissive
      environment in cohorts of adoptively transferred recipients. Intragraft
      expression of IL-2, IL-4, and IL-10 genes was diminished in euthymic and
      thymectomized tolerant hosts. However, grafts in the latter group showed
      significant IFN-gamma gene expression, suggesting a less efficient down
      regulation of Th1-like cells in the absence of regulatory cells. Indeed,
      exogenous challenge with rIL-2 or freshly alloactivated spleen cells recreated
      rejection in thymectomized, but not euthymic, hosts, suggesting that a state of
      cytokine-responsive anergy contributes to the "noninfectious" form of tolerance
      in thymectomized rats. The infection-tolerant state did not result from "graft
      adaptation," and regulatory T cells restricted for the original alloantigen were
      exposed to its continuous stimulation. The effective memory for suppression was
      dependent upon persistent donor-specific alloantigen stimulation; it disappeared
      within 3 weeks after its removal. Hence, both central and peripheral immune
      mechanisms, orchestrated by the tolerizing alloantigen, contribute to the
      infectious tolerance pathway in CD4 mAb-treated rat transplant recipients.

PMID- 9637487
TI  - IL-3 enhances both presentation of exogenous particulate antigen in association
      with class I major histocompatibility antigen and generation of primary tumor
      specific cytolytic T lymphocytes.
AB  - Recent studies have reported that APC can present particulate exogenous Ag in the
      context of class I MHC to CD8+ CTL, and our laboratory demonstrated that IL-3
      could enhance CTL generation to exogenous Ag. In this paper, we wished to
      determine whether presentation of particulate Ag could be enhanced by IL-3. A T
      cell hybridoma, B3Z86/90.14 (B3Z) restricted to Ova/Kb, was used as an indicator
      for presentation of particulate Ag with class I MHC. When activated, this
      hybridoma expresses lacZ, allowing a simple colorimetric measurement of Ag
      specific T cell stimulation. We demonstrated that bone marrow cells stimulated by
      IL-3 in vivo and in vitro exhibited significantly increased presentation of
      exogenous OVA linked to beads. Lysate from OVA-transfected line 1 murine lung
      adenocarcinoma cells (line 1/OVA) was also presented by IL-3-stimulated bone
      marrow cells, suggesting that these APC can process tumor fragments or debris.
      Studies using TAP1/2-deficient mice and Ag presentation inhibitors indicate that
      this exogenous Ag presentation is mediated via the conventional class I MHC
      pathway. Adoptive transfer of IL-3-stimulated bone marrow cells pulsed with
      lysate from line 1/OVA tumor cells into naive recipient mice led to the
      generation of a potent CTL response. These observations indicate that use of such
      cells may provide a new avenue for development of tumor vaccines.

PMID- 9637488
TI  - Cooperation between CD44 and LFA-1/CD11a adhesion receptors in lymphokine
      activated killer cell cytotoxicity.
AB  - IL-2-activated NK cells exhibit cytotoxic activity against a wide variety of
      tumor cells in a non-MHC-restricted fashion and in the absence of prior
      sensitization. The molecular mechanisms that regulate the cytotoxicity and
      attachment of activated killer cells to tumor target cells are not known. We
      provide genetic evidence in CD44(-/-) and LFA-1(-/-) mice that the cell adhesion
      receptors LFA-1 and CD44 regulate the cytotoxic activity of IL-2-activated NK
      cells against a variety of different tumor cells. This defect in cytotoxicity was
      significantly enhanced in mice that carried a double mutation of both CD44 and
      LFA-1. In vitro differentiation, TNF-alpha and IFN-gamma production, and
      expression of the cytolytic effector molecules perforin and Fas-L were comparable
      among IL-2-activated NK cells from LFA-1(-/-), CD44(-/-), CD44(-/-)LFA-1(-/-),
      and control mice. However, CD44(-/-), LFA-1(-/-), and CD44(-/-)LFA-1(-/-) IL-2
      activated NK cells showed impaired binding and conjugate formation with target
      cells. We also show that hyaluronic acid is the principal ligand on tumor cells
      for CD44-mediated cytotoxicity of IL-2-activated NK cells. These results provide
      the first genetic evidence of the role of adhesion receptors in IL-2-activated NK
      killing. These data also indicate that distinct adhesion receptors cooperate to
      mediate binding between effector and target cells required for the initiation of
      "natural" cytotoxicity.

PMID- 9637489
TI  - Differential involvement of a Fas-CPP32-like protease pathway in apoptosis of
      TCR/CD9-costimulated, naive T cells and TCR-restimulated, activated T cells.
AB  - Our previous study showed that CD9 costimulation of TCR-triggered naive T cells
      elicits activation ([3H]TdR incorporation) that is similar to CD28 costimulation;
      however, unlike CD28 costimulation, CD9 costimulation results in apoptosis of
      these previously activated T cells. Here, we investigated whether the apoptosis
      occurring after TCR/CD9 stimulation is associated with a death pathway involving
      Fas stimulation and Fas-mediated caspase activation as observed in activation
      induced cell death (AICD). In contrast to AICD, the apoptosis resulting from
      TCR/CD9 stimulation in C57BL/6 T cells was independent of Fas, because this form
      of apoptosis was not prevented by anti-Fas ligand mAb and was also induced in
      MRL/lpr T cells. AICD was observed at 12 h after the restimulation of activated T
      cells with anti-CD3 and reached a peak level at 24 h after this restimulation.
      CPP32-like protease activity was detected during AICD. Although TCR/CD9
      stimulation-associated apoptosis was observed at 24 h after the stimulation of
      naive T cells and reached a peak level at 36 h after this stimulation, CPP32-like
      protease activity in these T cells was only marginal at all time points.
      Nevertheless, both forms of apoptosis were prevented similarly by two different
      peptide-based caspase inhibitors. These results indicate that the apoptosis that
      follows the T cell activation which is induced as a result of CD9 costimulation
      does not involve a Fas-CPP32-like protease pathway, but suggest that different
      caspase members are likely to be critical in this form of apoptosis.

PMID- 9637490
TI  - Intracellular formation and cell surface expression of a complex of an intact
      lysosomal protein and MHC class II molecules.
AB  - The generation of invariant chain-free MHC class II molecules and their
      association with endocytically generated peptides are thought to occur in
      specialized lysosome-like compartments called MIICs (MHC class II compartments).
      A number of in vitro studies have shown that large denatured proteins can bind to
      class II molecules, and that class II association can protect the bound segment
      of protein from proteolytic degradation. In this work, we present what we believe
      is the first example of an intact endogenous protein (IP30) binding in an allele
      dependent fashion to class II molecules in vivo. IP30 is an IFN-gamma-inducible
      35-kDa glycoprotein that localizes in MIICs. In this study, we show that intact
      IP30 binds to certain HLA-DR alleles via an N-terminal prosequence. The
      association takes place in the endocytic pathway following removal of invariant
      chain from class II molecules and before their cell surface expression. We also
      show that DR-IP30 complexes are SDS stable. The potential precursor-product
      relationship between DR-IP30 complexes and the DR-peptide complex is discussed.

PMID- 9637491
TI  - Relationships among TCR ligand potency, thresholds for effector function
      elicitation, and the quality of early signaling events in human T cells.
AB  - Determining how receptor ligand quality and quantity together control the
      biologic responses of T cells is central to understanding normal and pathologic T
      cell immunity. Here we have carefully examined how variations in antigenic
      peptide structure and dose affect multiple functional responses of human T cell
      clones and have correlated these observations with proximal TCR signaling events
      induced by the same set of related ligands. As the Ag concentration increases,
      effector functions are elicited according to a clone-specific hierarchy. The
      absolute amount of each peptide required to stimulate the entire set of effector
      functions (potency) differs markedly among ligands for a single TCR, correlating
      with the efficiency of TCR down-modulation and the extent of ZAP-70 activation.
      However, distinct patterns of TCR zeta-chain phosphorylation were observed, with
      the ratios of TCRzeta isoforms relating to ligand agonist potency. The appearance
      of partially phosphorylated TCRzeta isoforms was paralleled by relative changes
      in certain response thresholds within the hierarchy. Thus, a combination of
      density, potency, and quality of signaling all contribute to the distinct effects
      of agonist ligands on T cell immunity.

PMID- 9637492
TI  - Expanding dendritic cells in vivo enhances the induction of oral tolerance.
AB  - The intestine is under perpetual challenge from both pathogens and essential
      nutrients, yet the mucosal immune system is able to discriminate effectively
      between harmful and innocuous Ags. It is likely that this selective
      immunoregulation is dependent on the nature of the APC at sites where gut Ags are
      processed and presented. Dendritic cells (DC) are considered the most potent of
      APC and are renowned for their immunostimulatory role in the initiation of immune
      responses. To investigate the role of DC in regulating the homeostatic balance
      between mucosal immunity and tolerance, we treated mice with Flt3 ligand (Flt3L),
      a growth factor that expands DC in vivo, and assessed subsequent systemic immune
      responsiveness using mouse models of oral tolerance. Surprisingly, mice treated
      with Flt3L to expand DC exhibited more profound systemic tolerance after they
      were fed soluble Ag. Most notably, tolerance could be induced in Flt3L-treated
      mice using very low doses of Ag that were ineffective in control animals. These
      findings contrast with the generally accepted view of DC as immunostimulatory APC
      and furthermore suggest a pivotal role for DC during the induction of tolerance
      following mucosal administration of Ag.

PMID- 9637493
TI  - NK cell modulation of murine cytomegalovirus retinitis.
AB  - CMV retinitis, the most common ophthalmic infection of AIDS patients, causes
      blindness if left untreated. To study the role of NK cells in the modulation of
      CMV ocular infection, 9.0 x 10(2) plaque-forming units of the Smith strain of
      murine CMV (MCMV) was injected into the supraciliary space of the left eyes of
      BALB/c mice. Lysis of NK-sensitive target cells (YAC-1) by effectors from the
      draining lymph nodes peaked at day 5 postinfection, while the splenic cytolytic
      response was biphasic, with peaks at days 2 and 7 postinfection. Flow cytometry
      showed that NK cells (DX-5+) increased in spleens and eyes 5 days after
      supraciliary infection with MCMV compared with uninfected or mock-infected
      controls. Eight days after supraciliary injection with 9.0 x 10(2) plaque-forming
      units of MCMV, 7 of 10 NK-depleted mice developed retinitis compared with only 2
      of 10 non-NK-depleted control mice. Poly(I-C) activation of NK cells in T cell
      depleted animals protected mice from MCMV retinitis; only 2 of 10 mice in the
      poly(I-C)-treated group developed retinitis compared with 8 of 10 T cell
      depleted, non-poly(I-C)-treated control mice. These results show the importance
      of NK cells in preventing MCMV retinitis and suggest that NK cells may also be
      involved in modulation of cytomegalovirus retinitis in human patients.

PMID- 9637494
TI  - T cell renewal rates, telomerase, and telomere length shortening.
AB  - Measurements on the average telomere lengths of normal human naive and memory T
      cells suggested that 1) naive and memory human T cells have similar division
      rates, and 2) that the difference between naive and memory cells reflects the
      degree of clonal expansion during normal immune reactions. Here we develop
      mathematic models describing how the population average of telomere length
      depends on the cell division rates of naive and memory T cells during clonal
      expansion and normal renewal. The results show that 1) telomeres shorten with
      twice the cell division rate, 2) that the conventional approach of estimating
      telomere length shortening per mean population doubling gives rise to estimates
      that are 39% larger than the "true" loss per cell division, 3) that naive and
      memory T cells are expected to shorten their telomeres at rates set by the
      division rate of the naive T cells only, i.e., irrespective of the division rate
      of memory T cells, 4) that the measured difference in the average telomere length
      between naive and memory T cells may largely reflect the difference in renewal
      rates between these subpopulations rather than the clonal expansion, and 5) that
      full telomerase compensation during clonal expansion is consistent with all data
      on the shortening of telomere length in, and between, naive and memory T cells.
      Thus we reconcile the apparent contradictions between the demonstrated difference
      in division rates between human naive and memory T cells and their similar rates
      of telomere shortening, and the demonstrated telomere shortening in the presence
      of telomerase activity.

PMID- 9637495
TI  - High frequency apoptosis of recent thymic emigrants in the liver of lymphopenic
      diabetes-prone BioBreeding rats.
AB  - Diabetes-prone (DP) BioBreeding (BB) rats develop spontaneous autoimmune
      diabetes. DP-BB thymocyte export is reduced, and most thymic emigrants disappear
      rapidly from peripheral lymphoid tissues. DP-BB rats are consequently lymphopenic
      and circulate severely reduced numbers of T cells. Peripheral T cells present are
      phenotypically immature (Thy1+) and appear activated. We hypothesized that DP-BB
      recent thymic emigrants have a shortened life span and disappear by apoptosis.
      The percentage of T cells with an alphabetaTCR(low) B220+ CD4- CD8- phenotype was
      increased in DP peripheral lymphoid tissues when compared with normal,
      nonlymphopenic diabetes-resistant (DR) BB rat tissues. There was no evidence of
      DNA fragmentation in freshly isolated DP- or DR-BB rat cells, but, after 24 h of
      culture, a higher proportion of DP- than DR-BB splenic T cells underwent
      apoptosis. We then tested the hypothesis that BB rat T cells with the
      alphabetaTCR(low) B220+ CD4- CD8- phenotype accumulate and undergo apoptosis in
      the liver. Such cells were observed undergoing apoptosis in both DP- and DR-BB
      rats, but comprised approximately 80% of intrahepatic T cells in DP vs
      approximately 20% in DR-BB rats. Most alphabetaTCR(low) B220+ CD4- CD8- cells in
      the liver were also Thy1+. The data suggest that T cell apoptosis in the DP-BB
      rat is underway in peripheral lymphoid tissues and is completed in the liver.
      Increased intrahepatic apoptosis of recent thymic emigrants appears in part
      responsible for lymphopenia in DP-BB rats and the concomitant predisposition of
      these animals to autoimmunity.

PMID- 9637496
TI  - The generation of human gammadelta T cell repertoires during fetal development.
AB  - The nature of how human gammadelta T cells are normally generated is not clear.
      We have used an RT-PCR assay and DNA sequencing to identify and compare delta
      encoded TCRs (TCRDs) that are generated de novo in the fetal gut, liver, and
      thymus and to determine when, where, and how the TCRD repertoire is established
      during normal embryonic development. Rearranged TCRDV genes are first expressed
      outside of the thymus in the liver and primitive gut between 6 and 9 wk
      gestation. Although DV1Rs and/or DV2Rs predominated, differences in the pattern
      of TCRDV gene rearrangement and transcription in each tissue during ontogeny were
      identified. Specific, DV2-encoded TCRs are highly conserved throughout ontogeny
      in the tissues from the same and between genetically distinct donors. Although
      the thymic and intestinal gammadelta T cell repertoires partially overlap early
      in development, they diverge and become nonoverlapping during the second
      trimester, and the generation of the intestinal gammadelta T cell repertoire is
      characterized by differences in the processing of DV1Rs and DV2Rs. Whereas the
      structural diversity of DV1Rs progressively increases during gut development up
      to birth, DV2Rs have limited structural diversity throughout ontogeny. Together,
      our findings provide evidence for the ability of different fetal tissues to
      support the development of gammadelta T cells.

PMID- 9637497
TI  - Exogenous and endogenous IL-10 regulate IFN-alpha production by peripheral blood
      mononuclear cells in response to viral stimulation.
AB  - IL-10 is an important regulator of the production of proinflammatory cytokines.
      Its effect on IFN-alpha production, however, has not been reported. In this
      study, PBMC from healthy donors were stimulated with virus in the presence of IL
      10. Human IL-10 (hIL-10) caused reductions in both the frequency of IFN-alpha
      producing cells (IPC) and bulk IFN in response to herpes simplex virus type-1
      (HSV-1), Sendai virus, Newcastle disease virus, and vesicular stomatitis virus.
      The inhibitory effect occurred when IL-10 was added 2 or 4 h before, or 2 h
      poststimulation with HSV or Sendai virus, but not when added 4 h postinduction.
      Unlike IL-10, IL-4 did not affect the IFN-alpha response to HSV. However, when
      PBMC were induced with Sendai virus, IFN-alpha production was also reduced by IL
      4. IL-10 treatment of PBMC resulted in strong reductions in the steady state
      levels of both HSV- and Sendai virus-induced IFN-alpha1, -alpha2, and -beta mRNA
      as determined by RT-PCR. IFN-alpha production to Sendai virus occurs
      predominantly by monocytes, whereas most enveloped viruses stimulate low
      frequency "natural IFN-producing cells (NIPC)," which are thought to be dendritic
      cells. Peripheral blood dendritic cells were found to express the IL-10 receptor,
      suggesting that IL-10 may directly act on the dendritic IPC. Addition of
      monoclonal anti-IL-10 to PBMC resulted in a significant increase in both the
      frequency of IPC and the amount of secreted IFN-alpha in response to HSV but not
      Sendai virus. We conclude that human IL-10 can serve as both an endogenous and
      exogenous regulator of IFN-alpha production.

PMID- 9637498
TI  - A pathogenic role of Th2 cells and their cytokine products on the pulmonary
      metastasis of murine B16 melanoma.
AB  - The role of Th2 cells and the cytokines produced by these cells on experimental
      pulmonary metastasis of B16 melanoma was investigated in a murine model implanted
      with high metastatic (B16F10) or low metastatic (B16F1) melanoma cells. An
      average of 250 colonies of metastasis in the lungs was counted in mice (BF10
      mice) at 14 days after the inoculation of 2 x 10(5) B16F10 cells/mouse, while <20
      colonies were detected in mice (BF1 mice) inoculated with the same number of
      B16F1 cells. CD4+ CD11b+ TCR-alphabeta+ T cells (BF10-Th2 cells) were produced in
      the spleens of BF10 mice, while these cells were not detected in BF1 mice. The
      BF10-Th2 cells produced IL-4 and IL-10 into culture fluids when stimulated in
      vitro with anti-CD3 mAb. However, IL-2 and IFN-gamma were not produced. The level
      of a pulmonary metastasis in BF1 mice increased to the level observed in BF10
      mice, when BF10-Th2 cells were adoptively transferred to BF1 mice. Also, an
      increase in the number of pulmonary melanoma was demonstrated in BF1 mice treated
      with 10 microg/kg murine rIL-4. The level of pulmonary metastasis in BF10 mice or
      in BF1 mice inoculated with BF10-Th2 cells decreased to the level observed in BF1
      mice when mice were treated with an anti-IL-4 mAb at a dose of 250 microg/kg on
      days 1, 3, and 5 after tumor inoculation. These results suggest that the severity
      of pulmonary metastasis in mice receiving B16 melanoma cells is strongly
      influenced by the IL-4 released from tumor-associated Th2 cells.

PMID- 9637499
TI  - IL-16 activates the SAPK signaling pathway in CD4+ macrophages.
AB  - IL-16 has been reported as a modulator of T cell activation and was shown to
      function as chemoattractant factor. The chemotactic activity of IL-16 depends on
      the expression of CD4 on the surface of target cells, but the intracellular
      signaling pathways are only now being deciphered. This report describes IL-16 as
      an additional activator of the stress-activated protein kinase (SAPK) pathway in
      CD4+ macrophages. Treatment of these cells with recombinant expressed IL-16 leads
      to the phosphorylation of SEK-1, resulting in activation of the SAPKs p46 and
      p54. IL-16 stimulation also leads to the phosphorylation of c-Jun and p38 MAPK
      (mitogen-activated protein kinase), without inducing MAPK-family members ERK-1
      and ERK-2. Interestingly, the IL-16-mediated activation of SAPKs and p38 MAPK in
      macrophages alone induces no detectable apoptotic cell death. These observations
      suggest specific regulatory functions of IL-16 distinct from the proinflammatory
      cytokines TNF-alpha and IL-1beta.

PMID- 9637500
TI  - Dipeptidyl peptidase I and granzyme A are coordinately expressed during CD8+ T
      cell development and differentiation.
AB  - Dipeptidyl peptidase I (DPPI) is a granule protease that plays a requisite role
      in processing the proenzyme form of the CTL granule serine proteases (granzymes).
      This study assesses DPPI mRNA and enzyme expression during T lymphocyte ontogeny
      and CTL differentiation. The most immature CD3- CD4- CD8- thymocytes were found
      to express >40-fold higher levels of DPPI mRNA, although levels of DPPI enzymatic
      activity in CD3- CD4- CD8- thymocytes were only modestly higher than those seen
      for CD4+ CD8+ or CD4+ CD8- thymocytes. More mature CD8+ CD4- thymocytes and CD8+
      splenocytes expressed significantly higher levels of DPPI mRNA and enzymatic
      activity than CD4+ CD8+ or CD4+ CD8- thymocytes. Granzyme A mRNA expression was
      observed in DPPI expressing CD3- CD4- CD8- and CD8+ CD4- thymocytes and was also
      observed in CD8+ CD4- splenocytes; however, expression was not observed in CD4+
      CD8+ or CD4+ CD8- thymocytes. Both DPPI mRNA and granzyme A mRNA expression in
      CD8+ T cells decreased to very low or undetectable levels during the first 48 h
      after allostimulation in MLCs. However, peak levels of both DPPI and granzyme A
      expression were observed later in the course of CD8+ T cell responses to
      alloantigen, with DPPI mRNA expression peaking on either day 3 or day 4 and
      granzyme A expression peaking at the end of a 5-day MLR. These data indicate that
      DPPI is expressed at all stages of T cell ontogeny and differentiation in which
      granzyme A mRNA is detected; consequently, DPPI appears to be available for the
      processing and activation of granzyme A during both CD8+ T cell development and
      differentiation.

PMID- 9637501
TI  - Stromal cell-independent maturation of IL-7-responsive pro-B cells.
AB  - The proliferation, survival, and differentiation of B cell progenitors in primary
      hematopoietic tissues depends on extracellular signals produced by stromal cells
      within the microenvironment. IL-7 is a stromal-derived growth factor that plays a
      crucial role in B lineage development. We have shown that in the presence of IL
      7, pro-B cells proliferate and differentiate to a stage in which they are
      responsive to stromal cells and LPS, leading to terminally differentiated IgM
      secreting plasma cells. In this report, we examine in detail the role of stromal
      cells in the transition from the IL-7-responsive pro-B cell stage to the mature
      LPS-responsive B cell stage. We demonstrate that this transition fails to occur,
      even in the presence of stromal cells and LPS, if constant exposure to IL-7 is
      maintained. The transition from the large pro-B cell stage to the small cmu+ pre
      B cell stage occurs independent of stromal cells. Moreover, the "stromal cell
      dependent" maturation that occurs subsequent to the expression of surface IgM
      leading to responsiveness to B cell mitogens can also be accomplished in the
      absence of stromal cells if pre-B cells are cultured in proximity to each other
      or at high cell concentrations. Together these results suggest that stromal cells
      mediate B cell differentiation by providing the necessary growth requirements
      (i.e., IL-7) to sustain the development of pre-B cells. The progeny of these pre
      B cells can then differentiate through as yet unidentified homotypic
      interactions, leading to the production of LPS-responsive B cells.

PMID- 9637502
TI  - CpG oligodeoxyribonucleotides rescue mature spleen B cells from spontaneous
      apoptosis and promote cell cycle entry.
AB  - Isolated murine splenic B cells undergo spontaneous apoptosis. Motifs containing
      unmethylated CpG dinucleotides in bacterial DNA or in synthetic
      oligodeoxynucleotides (ODN) are known to activate murine B cells. Now we show
      that ODN that induce spleen B cell cycle entry also inhibit spontaneous apoptosis
      in a sequence-specific fashion. Reversal of the CG to GC abolished activity.
      Methylation of the central cytosine decreased activity. When CpG is preceded by a
      cytosine or followed by a guanine, activity was abolished. Other substitutions at
      the same positions had no effect. Dose-response curves for apoptosis protection
      and G1 entry suggested that a uniform population of ODN recognition sites
      controlled downstream ODN effects. A CpG ODN with a nuclease-resistant
      phosphorothioate backbone (S-ODN) was also active, and increased the levels of c
      myc, egr-1, c-jun, bclXL, and bax mRNA and c-Myc, c-Jun, Bax, and BclXL protein
      in spleen B cells. Levels of c-myb, myn, c-Ki-ras, and bcl2 mRNA remained
      unchanged. When protein synthesis was inhibited, at 16 h ODN-induced cell cycle
      entry was abolished and apoptosis protection was partially preserved. Under these
      conditions, c-Myc was still present, but c-Jun and BclXL were not detected. Our
      results suggest that CpG containing ODN motifs provide signals for both survival
      and cell cycle entry. Single base changes determine whether this signal proceeds
      through a rate-limiting step governing at least two steps in apoptosis (plasma
      membrane transition, DNA cleavage) and two phases of the cell cycle (G1 and S
      phase entry). This biologic action is associated with increased c-Myc, c-Jun, and
      BclXL expression.

PMID- 9637503
TI  - The regulation of murine H-2Dd expression by activation transcription factor 1
      and cAMP response element binding protein.
AB  - Resistance to radiation leukemia virus (RadLV)-induced leukemia is correlated
      with an increase in H-2Dd expression on the thymocyte surface. It has been shown
      that elevated H-2Dd expression on infected thymocytes is a result of elevated
      mRNA transcription and that the transcriptional increase is correlated with
      elevated levels of a DNA binding activity, H-2 binding factor 1 (H-2 BF1), which
      recognizes the 5'-flanking sequence (5'-TGACGCG-3') of the H-2Dd gene. Recently,
      it has been shown that the activation transcription factor 1 (ATF-1) homodimer is
      one form of the H-2 BF1 complex. Here we demonstrate that the cAMP response
      element binding protein (CREB) homodimer and the heterodimer of CREB/ATF-1 also
      recognize the cis regulatory motif and are two additional forms of the H-2 BF1
      complex. The levels of mRNA encoding ATF-1 and CREB were both increased in RadLV
      infected thymocytes that showed increased levels of H-2 mRNA. Also, all three H-2
      BF1 binding activities, ATF-1 homodimer, CREB homodimer, and ATF-1/CREB
      heterodimer, were increased in RadLV-infected thymocytes that expressed high
      levels of H-2Dd Ag on the cell surface. Transfection experiments demonstrated
      that ATF-1 and CREB activated a reporter plasmid containing the H-2 BF1 motif.
      These observations strongly suggest that both ATF-1 and CREB are involved in the
      regulation of H-2 gene expression following RadLV infection of mouse thymocytes.

PMID- 9637504
TI  - Expression and characterization of recombinant soluble peptide: I-A complexes
      associated with murine experimental autoimmune diseases.
AB  - Structural and functional studies of murine MHC class II I-A molecules have been
      limited by the low yield and instability of soluble, recombinant heterodimers. In
      the murine autoimmune diseases experimental autoimmune encephalomyelitis and
      collagen-induced arthritis, MHC class II molecules I-Au and I-Aq present peptides
      derived from myelin basic protein and type II collagen, respectively, to
      autoreactive T cells. To date, systems for the expression of these two I-A
      molecules in soluble form for use in structure-function relationship studies have
      not been reported. In the present study, we have expressed functional I-Au and I
      Aq molecules using a baculovirus insect cell system. The chain pairing and
      stability of the molecules were increased by covalently linking the antigenic
      peptides to beta-chains and adding carboxyl-terminal leucine zippers. Peptide:I
      Aq complex quantitatively formed an SDS-stable dimer, whereas peptide:I-Au formed
      undetectable amounts. However, the two complexes did not show any significant
      difference in their response to thermal denaturation as assessed by circular
      dichroism analyses. The autoantigen peptide:I-A complexes were highly active in
      stimulating cognate T cells to secrete IL-2 and inducing Ag-specific apoptosis of
      the T cells. Interestingly, the T cells were stimulated by these soluble
      molecules in the apparent absence of experimentally induced cross-linking of
      TCRs, indicating that they may have therapeutic potential in autoimmune disease
      models.

PMID- 9637505
TI  - HLA-G isoforms produced by placental cytotrophoblasts and found in amniotic fluid
      are due to unusual glycosylation.
AB  - The human placenta expresses HLA-G, a nonclassical (class Ib) MHC molecule that
      could play a central role in maternal tolerance of the semiallogeneic fetus. In
      this work, we report the production of a new mAb, 4H84, that specifically reacts
      with HLA-G in two formats: immunocytochemistry and immunoblotting.
      Immunolocalization experiments with 4H84 confirmed our previous finding that
      cytotrophoblasts within the uterine wall are the only cells in tissue sections of
      placenta that express the HLA-G protein. Additional experiments showed that both
      amniocytes and cytotrophoblasts in the amnion-chorion express this protein. Since
      multiple HLA-G transcripts have been described, we used immunoblotting to study
      the HLA-G isoforms produced by cytotrophoblasts in vitro and by the amnion
      chorion in vivo. Cytotrophoblasts, their conditioned medium, and amniotic fluid
      samples contained heterodisperse immunoreactive bands (Mr 35,000-50,000). N
      deglycosylation by peptide-N-glycosidase F digestion resolved these isoforms into
      two distinct bands. Cell samples contained primarily an Mr 37,000-42,000 protein,
      most likely encoded by the full-length mRNA. Conditioned medium and amniotic
      fluid contained a slightly smaller protein, most likely the secreted form lacking
      the transmembrane and cytoplasmic regions. Removal of polylactosamine chains by
      endo-beta D-galactosidase digestion significantly reduced the electrophoretic
      mobility of the immunoreactive bands, suggesting that HLA-G, unlike class Ib
      molecules studied to date, carries N-acetyllactosamine units. These data show
      that Mr heterogeneity of HLA-G is due to its novel glycosylation, rather than to
      the translation of alternatively spliced mRNAs. We postulate that the unusual
      carbohydrate structures this molecule carries could interact with maternal immune
      cells and/or stabilize the molecule.

PMID- 9637506
TI  - Failure to activate cytosolic phospholipase A2 causes TNF resistance in human
      leukemic cells.
AB  - Activation of cytosolic phospholipase A2 (cPLA2) by TNF has been shown to be an
      important component of the signaling pathway leading to cell death. The role of
      cPLA2 in the cytotoxic action of TNF was investigated in a panel of human
      leukemic cell lines. TNF could activate cPLA2 only in U937 and HL60 TNF-sensitive
      leukemic cells, but not in KG1a, CEM, and CEM/VLB100 cells that are relatively
      resistant to TNF. Pretreatment with 4-bromophenacyl bromide, a cPLA2 inhibitor,
      rendered U937 and HL60 cell lines resistant to the cytotoxic effect of TNF.
      Immunoblot and reverse-transcriptase PCR demonstrated that cPLA2 expression was
      detectable at both transcriptional and translational levels in all leukemic cell
      lines studied, although CEM and CEM/VLB100 cells expressed cPLA2 mRNA and protein
      at lower levels. The protein synthesis inhibitor, cycloheximide, increased TNF
      induced cPLA2 activity and cytotoxicity in both CEM and CEM/VLB100 cell lines.
      Low levels of cPLA2 activity in the KG1a cell line could be activated by the
      cPLA2 activator mellitin, or the calcium ionophore A23187. The data suggest that
      cPLA2 activity is involved in TNF-induced cytotoxicity in leukemic cells.
      Resistance to TNF-induced cytotoxicity may involve either protein inhibitors that
      act upstream of cPLA2 in the TNF-signaling pathway or constitutive defects of
      cPLA2 itself, possibly involving calcium utilization.

PMID- 9637507
TI  - Molecular mechanisms of the induction of IL-12 and its inhibition by IL-10.
AB  - Exogenously added IL-10 rapidly inhibited Staphylococcus aureus- or LPS-induced
      cytokine mRNA expression in human PBMCs and monocytes, with a maximal effect
      observed when IL-10 was added from 20 h before until 1 h after the addition of
      the inducers. Nuclear run-on assays revealed that the inhibition of IL-12 p40, IL
      12 p35, and TNF-alpha was at the gene transcriptional level and that the addition
      of IL-10 to S. aureus- or LPS-treated PBMCs did not affect mRNA stability. The
      inhibitory activity of IL-10 was abrogated by cycloheximide (CHX), suggesting the
      involvement of a newly synthesized protein(s). The addition of CHX at 2 h before
      S. aureus or LPS also inhibited the accumulation of IL-12 p40 mRNA, but did not
      inhibit IL-12 p35 and TNF-alpha mRNA. This finding suggests that p40
      transcription is regulated through a de novo synthesized protein factor(s),
      whereas the addition of CHX at 2 h after S. aureus activation caused
      superinduction of the IL-12 p40, IL-12 p35, and TNF-alpha genes. These results
      indicate that in human monocytes, the mechanism(s) of IL-10 suppression of both
      IL-12 p40 and IL-12 p35 genes is primarily seen at the transcriptional level, and
      that the induction of the IL-12 p40 and p35 genes have different requirements for
      de novo protein synthesis.

PMID- 9637508
TI  - Conservation of structure and function between human and murine IL-16.
AB  - IL-16 is a proinflammatory cytokine that signals via CD4, inducing chemotactic
      and immunomodulatory responses of CD4+ lymphocytes, monocytes, and eosinophils.
      Comparative analysis of murine and human IL-16 homologs could reveal conserved
      structures that would help to identify key functional regions of these cytokines.
      To that end, we cloned the murine IL-16 cDNA and found a high degree of amino
      acid similarity comparing the predicted murine and human IL-16 precursor proteins
      (pro-IL-16). The highest similarity (82.1%) was found in the C-terminal region,
      which is cleaved from pro-IL-16 to yield biologically active IL-16. Chemotaxis
      experiments with IL-16 of murine and human origin, using murine splenocytes or
      human T lymphocytes as targets, showed cross-species stimulation of motility.
      Synthetic oligopeptides and anti-peptide Ab were produced, based on the sequences
      of three predicted hydrophilic domains of IL-16 potentially presented in exposed
      positions. None of these peptides had intrinsic IL-16 bioactivity, but one
      (corresponding to a hydrophilic C-terminal domain of IL-16) partially displaced
      binding of OKT4 mAb to human lymphocytes. This peptide, and its cognate Ab, also
      inhibited IL-16 chemoattractant activity for human and murine cells. These
      studies demonstrate a high degree of structural and functional similarity between
      human and murine IL-16 and suggest that amino acids in the C terminus are
      critical for its chemoattractant function. The data suggest cross-species
      conservation of IL-16 receptor structures as well. Inhibitory peptides may be
      useful in disease states where the proinflammatory functions of IL-16 are
      detrimental to the host.

PMID- 9637509
TI  - The effect of gammadelta T cell depletion on cytokine gene expression in
      experimental allergic encephalomyelitis.
AB  - In experimental autoimmune encephalomyelitis (EAE), a model for multiple
      sclerosis, we showed previously that depletion of gammadelta T cells using the
      mAb GL3 immediately before disease onset, or during the chronic phase,
      significantly ameliorated clinical severity. We now report on the effect of
      gammadelta T cell depletion on expression of five cytokine genes, IL-1, IL-6,
      TNF, lymphotoxin, and IFN-gamma in spinal cords of mice during the pre-onset,
      onset, height, and recovery phases of EAE, and on expression of type II nitric
      oxide synthase. In control animals, the mRNAs for IL-1 and IL-6 rose dramatically
      at disease onset and peaked before disease height, whereas the mRNAs for TNF,
      lymphotoxin, and IFN-gamma rose more slowly and peaked with peak of disease. In
      GL3-treated animals, a dramatic reduction in all five cytokines was noted at
      disease onset, but only IFN-gamma remained significantly reduced at a time point
      equivalent to height of disease in control animals. ELISA data confirmed the
      reduced levels of IL-1 and IL-6 at disease onset in GL3-treated animals, and
      pathologic analysis demonstrated a marked reduction in meningeal infiltrates at
      the same time point. Studies of type II NOS also demonstrated a significant
      reduction in both mRNA and protein expression at the height of disease in GL3
      treated animals. These results suggest that gammadelta T cells contribute to the
      pathogenesis of EAE by regulating the influx of inflammatory cells into the
      spinal cord and by augmenting the proinflammatory cytokine profile of the
      inflammatory infiltrates.

PMID- 9637510
TI  - Inefficient assembly and intracellular accumulation of antibodies with mutations
      in V(H) CDR2.
AB  - We previously described secretion defects in four mutants of the murine anti
      phosphocholine Ab, T15. The mutant heavy (H) chains had amino acid replacements
      in the V(H) complementarity-determining region 2 (HCDR2) and were expressed at
      normal intracellular levels. Here, the intracellular fate of the secretion
      defective mutant heavy chains was investigated. Metabolic labeling demonstrated
      that the T15 wild-type Ab was secreted within a 4-h chase. In contrast, the
      mutant H chains accumulated with intracellular t(1/2) values ranging from 10 to
      24 h. The mutant H chains were associated with increased levels of the molecular
      chaperones BiP and GRP94, and remained endoglycosidase H sensitive, suggesting
      retention in the endoplasmic reticulum. Assembly of the mutant H chains with T15
      light (L) chain was arrested at the H2 and H2L intermediate stages of the T15
      wild-type pathway (H2 --> H2L --> H2L2). Even though some assembly with L chain
      occurred, it was not as a secretion-competent H2L2 Ig moiety. The T15 L chains
      coexpressed with mutant H chains were degraded efficiently except for a minor L
      chain population with a long t(1/2) that was apparently protected at the H2L
      stage. To our knowledge, this is the first study demonstrating that intracellular
      half-lives of Ig H and L chains can be influenced by somatic mutations in HCDR2.

PMID- 9637512
TI  - Structural and functional analysis of J chain-deficient IgM.
AB  - Previous studies have discerned two forms of polymeric mouse IgM: moderately
      cytolytic (complement-activating) pentamer, which contains J chain, and highly
      cytolytic hexamer, which lacks J chain. To investigate the relationships among
      polymeric structure, J chain content, and cytolytic activity, we produced IgM in
      J chain-deficient and J chain-proficient mouse hybridoma cell lines. Both hexamer
      and pentamer were produced in the absence as well as the presence of J chain.
      Hexameric IgM activated (guinea pig) complement approximately 100-fold more
      efficiently than did J chain-deficient pentamer, which, in turn, was more active
      than J chain-containing pentamer. These results are consistent with the
      hypothesis that J chain-containing pentamer cannot activate complement. We also
      analyzed the structure of IgM-S337, in which the mu-chain bears the C337S
      substitution. Like normal IgM, IgM-S337 was formed as a hexamer and as both J
      chain deficient- and J chain-containing pentamers. Unlike normal IgM, IgM-S337
      dissociated in SDS into various subunits. For IgM-S337 pentamer, the predominant
      subunits migrated as mu2kappa2 and mu4kappa4, and the subunit distribution was
      unaltered by J chain. However, J chain was found only in the mu2kappa2 species,
      suggesting that some arrangement of inter-mu bonds directs incorporation of J
      chain. IgM-S337 hexamer also dissociated to mu2kappa2 and mu4kappa4, but also
      yielded several species migrating much more slowly in SDS-PAGE than wild-type
      mu12kappa12. To account for these forms, we propose that each mu-chain can
      interact with three other mu-chains and that some hexameric molecules contain two
      catenated mu6kappa6 circles.

PMID- 9637511
TI  - The alpha2 domain of H-2Dd restricts the allelic specificity of the murine NK
      cell inhibitory receptor Ly-49A.
AB  - Mouse NK lymphocytes express Ly-49 receptors, which inhibit cytotoxicity upon
      ligation by specific MHC I molecules on targets. Different members of the lectin
      like mouse Ly-49 receptor family recognize distinct subsets of murine H-2
      molecules, but the molecular basis for the allelic specificity of Ly-49 has not
      been defined. We analyzed inhibition of natural killing by chimeric MHC I
      molecules in which the alpha1, alpha2, or alpha3 domains of the Ly-49A-binding
      allele H-2Dd were exchanged for the corresponding domains of the nonbinding
      allele H-2Db. Using the Ly-49A-transfected rat NK cell line, RNK-mLy-49A.9, we
      demonstrated that the H-2Dd alpha2 domain alone accounts for allelic specificity
      in protection of rat YB2/0 targets in vitro. We also showed that the H-2Dd alpha2
      domain is sufficient to account for the allele-specific in vivo protection of H
      2b mouse RBL-5 tumors from NK cell-mediated rejection in D8 mice. Thus, in
      striking contrast to the alpha1 specificity of Ig-like killer inhibitory
      receptors for human HLA, the lectin-like mouse Ly-49A receptor is predominantly
      restricted by the H-2Dd alpha2 domain in vitro and in vivo.

PMID- 9637513
TI  - Structural requirements for a specificity switch and for maintenance of affinity
      using mutational analysis of a phage-displayed anti-arsonate antibody of Fab
      heavy chain first complementarity-determining region.
AB  - We previously showed that a single mutation at heavy (H) position 35 of Abs
      specific for p-azophenylarsonate (Ars) resulted in acquisition of binding to the
      structurally related hapten p-azophenylsulfonate (Sulf). To explore the sequence
      and structural diversity of the H chain first complementarity-determining region
      (HCDR1) in modulating affinity and specificity, positions 30-36 in Ab 36-65 were
      randomly mutated and expressed as Fab in a bacteriophage display vector. Ab 36-65
      is germline encoded, lacking somatic mutations. Following affinity selection on
      Sulf resins, 55 mutant Fab were isolated, revealing seven unique HCDR1 sequences
      containing different amino acids at position H:35. All Fab bound Sulf, but not
      Ars. Site-directed mutagenesis in a variety of HCDR1 sequence contexts indicates
      that H:35 is critical for hapten specificity, independent of the sequence of the
      remainder of HCDR1. At H:35, Asn is required for Ars specificity, consistent with
      the x-ray crystal structure of the somatically mutated anti-Ars Ab 36-71, while
      Sulf binding occurs with at least seven different H:35 residues. All Sulf-binding
      clones selected following phage display contained H:Gly33, observed previously
      for Ars-binding Abs that use the same germline V(H) sequence. Site-directed
      mutagenesis at H:33 indicates that Gly plays an essential structural role in
      HCDR1 for both Sulf- and Ars-specific Abs.

PMID- 9637515
TI  - Mechanisms of macrophage stimulation through CD8: macrophage CD8alpha and CD8beta
      induce nitric oxide production and associated killing of the parasite Leishmania
      major.
AB  - Prior studies demonstrated that rat macrophages express CD8, which differs from T
      lymphocyte CD8 within the ligand binding domain. We investigated whether
      stimulation of macrophage CD8 could induce mediator release and regulate host
      defense. Cross-linking either CD8alpha (OX8, 5 microg/ml) or CD8beta (341, 10
      microg/ml) stimulated nitric oxide (NO) production, which correlated with an up
      regulation of inducible NO synthase protein. Cell signaling inhibitors were used
      to elucidate the pathways of CD8alpha and CD8beta stimulation. Genistein (broad
      spectrum protein tyrosine kinase inhibitor, 10 microg/ml), PP1 (src family kinase
      inhibitor, 5 microg/ml), polymyxin B (protein kinase C (PKC) inhibitor, 100
      microg/ml), and Ro 31-8220 (PKC inhibitor, 1 microM) significantly inhibited anti
      CD8alpha- and anti-CD8beta-stimulated NO production and inducible NO synthase up
      regulation, suggesting that tyrosine kinase(s) (src family) and PKC are involved
      in CD8 signaling. In addition, cross-linking CD8alpha stimulated NO-dependent
      macrophage killing of the parasite Leishmania major. For the first time, this
      work demonstrates that the beta-chain of macrophage CD8, in addition to the alpha
      chain, can regulate mediator release. These results further illustrate the
      importance of this molecule and support our previous data demonstrating
      differences between macrophage and T lymphocyte CD8. Additional studies on the
      signaling mechanisms and possible ligand(s) for macrophage CD8 will lead to a
      greater understanding of inflammation and host defense.

PMID- 9637514
TI  - Role of mucosal immunity in herpes simplex virus infection.
AB  - This study evaluates whether the vaginal mucosal surface of immunized mice can
      prevent invasion by herpes simplex virus (HSV) and aims to identify immune
      components that affect immunity after challenge at the vaginal mucosa. Despite
      the induction of both IgA and IgG vaginal Ab following immunization with
      recombinant vaccinia virus vectors expressing either glycoproteins B or D, viral
      infection occurred in most animals even after minimal viral dose challenge.
      Challenged immune animals, including those genetically unable to generate anti
      HSV Ab, survived and showed few if any clinical signs of infection. Experiments
      with T cell subtype knockout animals and depletion with T cell subset-specific
      MAb indicated that immunity following vaginal challenge was principally dependent
      on the function of CD4+ T cells. Our results indicate that anti-HSV vaccines may
      not provide barrier immunity at the vaginal mucosal site but may be adequate to
      minimize clinical expression of disease.

PMID- 9637516
TI  - The role of T cells in allografted tumor rejection: IFN-gamma released from T
      cells is essential for induction of effector macrophages in the rejection site.
AB  - Allografted Meth A tumor rejection is T cell dependent, but T cells are inactive
      toward the allograft; rather, the main effector cells are allograft-induced
      macrophages (AIM) with MHC haplotype specificity. Here, we examined the role of T
      cells in the induction of AIM in the rejection site. On day 4.5 after i.p.
      transplantation of Meth A fibrosarcoma cells to C57BL/6 (B6) mice, we obtained a
      kind of precursor of AIM (pro-AIM) from the transplantation site by an enrichment
      technique involving adherence to serum-coated dishes. The noncytotoxic pro-AIM
      rich population put into a diffusion chamber became cytotoxic against Meth A
      cells after 2 days in the peritoneal cavity of an untreated B6 mouse. Similar
      activation of the chambered B6 pro-AIM-rich population occurred in IFN-gamma -/-
      B6 mice, whereas there was no activation when chambers containing an IFN-gamma -/
      mouse-derived pro-AIM-rich population were placed in normal or IFN-gamma -/-
      mice, suggesting that IFN-gamma is involved in the activation. RT-PCR experiments
      demonstrated that among bulk infiltrates T cells were the major producer of IFN
      gamma; and most of the cells in a T cell-eliminated pro-AIM population in a
      diffusion chamber kept for 2 days in a B6 mouse did not become AIM. Furthermore,
      IFN-gamma -/- B6 mice could not reject allografted Meth A tumor cells, whereas
      the grafts were rejected by i.p. injections of IFN-gamma into the mutant mice.
      These results indicate that IFN-gamma released from allograft-induced T cells is
      essential for both the activation of a kind of pro-AIM to AIM in the
      transplantation site and the rejection of an allografted tumor.

PMID- 9637517
TI  - Mucosal addressin is required for the development of diabetes in nonobese
      diabetic mice.
AB  - Immune responses are best initiated in the environment of lymphoid tissues
      wherein circulating lymphocytes enter by interacting with endothelial adhesion
      molecules. In type 1 diabetes, immune responses against pancreatic islets
      develop, but the environment in which this occurs remains unidentified. To
      determine whether lymphocyte homing to lymphoid organs is involved in the
      pathogenesis of diabetes in nonobese diabetic (NOD) mice, we blocked the function
      of the mucosal addressin cell adhesion molecule-1 (MAdCAM-1), which is a vascular
      addressin-mediating lymphocyte homing into mucosal lymphoid tissues, in these
      mice. While ineffective if started later, a blockade started at 3 wk of age
      reduced the incidence of diabetes from 50% to 9% (p < 0.01). This finding is
      associated with Peyer's patch atrophy, a marked decrease of naive (CD44(low)
      CD45RB(high)) T lymphocytes, and a reduction in the relative numbers of memory
      (CD44(high)) T lymphocytes in the spleen. The potential of these spleen cells to
      cause diabetes was diminished. Anti-MAdCAM-1 treatment also inhibited both
      lymphocyte entry into the pancreas and diabetes development in NOD/SCID
      recipients after the transfer of lymphocytes derived from the mesenteric lymph
      nodes of young, but not of diabetic, NOD donors. Therefore, MAdCAM-1 may be
      required during two distinct steps in an early phase of diabetes development: for
      the entry of naive lymphocytes into the lymphoid tissues in which diabetes
      causing lymphocytes are originally primed, and for the subsequent homing of these
      lymphocytes into the pancreas. The role of MAdCAM-1 as a mucosal vascular
      addressin suggests that mucosal lymphoid tissues are involved in the initiation
      of pathologic immune responses in NOD mice.

PMID- 9637518
TI  - The antibody response to fungal melanin in mice.
AB  - Melanins are associated with virulence in several important human pathogens, but
      little is known about the immune response to this ubiquitous biologic compound.
      We hypothesized that melanin produced by the fungus Cryptococcus neoformans was
      immunogenic. C. neoformans melanin was purified from melanized fungal cells and
      was used to immunize C57BL/6, BALB/c, and T cell-deficient (nude) BALB/c mice.
      The Ab response was evaluated by ELISA, immunofluorescence, and agglutination.
      The results demonstrate that melanin can be immunogenic, and the humoral immune
      response is T cell independent. Furthermore, the experiments demonstrate 1) a
      sensitive ELISA for the measurement of Ab to melanin, 2) that mice mount an
      intense Ab response to fungal melanin that includes Abs of IgM and IgG isotypes,
      3) that melanins from different sources have cross-reactive epitopes, and 4)
      melanin in the cell wall of melanized yeast cells reacts with Abs raised to L
      dopa C. neoformans melanin. The biologic significance of Ab to melanin remains to
      be determined, but the development of Ab suggests that this amorphous insoluble
      polymer can stimulate the immune system. The serologic techniques described here
      may prove useful for the evaluation of Ab responses to melanin in a variety of
      diseases.

PMID- 9637519
TI  - Influenza A virus-induced IFN-alpha/beta and IL-18 synergistically enhance IFN
      gamma gene expression in human T cells.
AB  - T cells contribute significantly the to host's early defense against viral and
      bacterial infections and are essential for clearance of the pathogen. IFN-gamma,
      a product of activated T and NK cells, has, in addition to its direct
      antimicrobial activity, a major role in activating cell-mediated immunity. Here
      we report that cytokines secreted by influenza A virus-infected macrophages are
      able to induce IFN-gamma synthesis in human T cells. Influenza A virus-infected
      human peripheral macrophages secreted IFN-alpha/beta, TNF-alpha, IL-1beta, and a
      recently identified cytokine, IL-18 (or IFN-gamma-inducing factor), whereas the
      production of IL-12 was not detected. Supernatants collected from virus-infected
      macrophages induced rapid IFN-gamma mRNA expression and protein production in T
      cells. This was down-regulated by the addition of neutralizing anti-IFN
      alpha/beta Abs, whereas neutralizing anti-IL-12 Abs had no effect on IFN-gamma
      gene expression. Exogenously added IFN-alpha/beta also rapidly stimulated the
      synthesis of IFN-gamma mRNA in T cells independently of protein synthesis. IL-18
      synergized with IFN-alpha to up-regulate IFN-gamma gene expression and protein
      production. The data suggest that IFN-alpha/beta and IL-18 produced by
      macrophages during virus infection may act together to induce IFN-gamma synthesis
      and, consequently, may play an important role for both of these cytokines in the
      development of Th1-type immune responses.

PMID- 9637520
TI  - Clostridium difficile toxin A stimulates macrophage-inflammatory protein-2
      production in rat intestinal epithelial cells.
AB  - Neutrophil infiltration of the colonic mucosa is a hallmark of Clostridium
      difficile toxin A-mediated enterocolitis. Macrophage-inflammatory protein-2 (MIP
      2) is a potent neutrophil chemoattractant secreted by rat macrophages and
      epithelial cells in response to inflammatory stimuli. In this work, we report
      that administration of toxin A into rat ileal loops increased mucosal levels of
      MIP-2 before the onset of fluid secretion and mucosal neutrophil infiltration.
      Administration of rabbit anti-MIP-2 IgG, but not control IgG, reduced toxin A
      mediated secretion (by 58%), mucosal permeability (by 80%), and myeloperoxidase
      activity (by 85%). Immunohistochemical analysis demonstrated increased MIP-2
      expression in intestinal epithelial and lamina propria cells 1 h after toxin A
      administration. Intestinal epithelial cells purified from toxin A-exposed ileal
      loops also showed increased MIP-2 mRNA expression and MIP-2 protein release that
      was inhibited by pretreatment of rats with the transcriptional inhibitor
      actinomycin D. These results indicate that C. difficile toxin A induces MIP-2
      release from intestinal epithelial cells and that MIP-2 contributes to neutrophil
      mucosal influx during toxin A enteritis.

PMID- 9637521
TI  - Th1 cells specific for a secreted protein of Listeria monocytogenes are
      protective in vivo.
AB  - In the present study we have investigated the role of the secreted p60 protein
      from Listeria monocytogenes as an Ag for CD4 T cells. The p60 protein is an
      abundant extracellular protein that is highly conserved within the members of the
      genus Listeria. Our results show that L. monocytogenes infection induces a potent
      p60-specific Th1 immune response. Remarkably, we found that p60-specific Th1
      clones mediate significant protection against L. monocytogenes infection. For one
      p60-specific clone, the peptide epitope was defined. This clone recognized p60
      301-312 (EAAKPAPAPSTN) in the context of the H-2Ad molecule. Despite the fact
      that acquired immunity against L. monocytogenes is primarily mediated by
      cytotoxic CD8 T lymphocytes, our data clearly demonstrate that secreted bacterial
      proteins are important CD4 T cell Ags and that Th1 clones specific for a secreted
      bacterial protein can contribute to the protection against an intracellular
      pathogen such as L. monocytogenes.

PMID- 9637522
TI  - IL-6 produced by Kupffer cells induces STAT protein activation in hepatocytes
      early during the course of systemic listerial infections.
AB  - Kupffer cells were the principal source of IL-6 produced in the livers of mice
      following i.v. inoculation of Listeria monocytogenes. IL-6 mRNA expression and
      the production of IL-6 were reduced drastically within the nonparenchymal liver
      cell population derived from mice rendered Kupffer cell depleted by pretreatment
      with liposome-encapsulated dichloromethylene diphosphonate. A sharp increase in
      the appearance of activated STAT3 occurred in extracts of purified hepatocytes
      derived from normal mice infected i.v. with Listeria. Remarkably, the kinetics of
      this increase overlapped IL-6 mRNA expression by Kupffer cells; each peaked at
      approximately 30 min postinfection. No increase in STAT3 activation was observed
      in IL-6-deficient or Kupffer cell-depleted animals. The results of these
      experiments indicate that the synthesis of IL-6 and the activation of STAT3
      within hepatocytes are critical functions of Kupffer cells occurring very early
      during the course of systemic listerial infections.

PMID- 9637523
TI  - Characterization of the peptide binding motif of a rhesus MHC class I molecule
      (Mamu-A*01) that binds an immunodominant CTL epitope from simian immunodeficiency
      virus.
AB  - The majority of immunogenic CTL epitopes bind to MHC class I molecules with high
      affinity. However, peptides longer or shorter than the optimal epitope rarely
      bind with high affinity. Therefore, identification of optimal CTL epitopes from
      pathogens may ultimately be critical for inducing strong CTL responses and
      developing epitope-based vaccines. The SIV-infected rhesus macaque is an
      excellent animal model for HIV infection of humans. Although a number of CTL
      epitopes have been mapped in SIV-infected rhesus macaques, the optimal epitopes
      have not been well defined, and their anchor residues are unknown. We have now
      defined the optimal SIV gag CTL epitope restricted by the rhesus MHC class I
      molecule Mamu-A*01 and defined a general peptide binding motif for this molecule
      that is characterized by a dominant position 3 anchor (proline). We used peptide
      elution and sequencing, peptide binding assays, and bulk and clonal CTL assays to
      demonstrate that the optimal Mamu-A*01-restricted SIV gag CTL epitope was
      CTPYDINQM(181-189). Mamu-A*01 is unique in that it is found at a high frequency
      in rhesus macaques, and all SIV-infected Mamu-A*01-positive rhesus macaques
      studied to date develop an immunodominant gag-specific CTL response restricted by
      this molecule. Identification of the optimal SIV gag CTL epitope will be critical
      for a variety of studies designed to induce CD8+ CTL responses specific for SIV
      in the rhesus macaque.

PMID- 9637524
TI  - Blockade of endogenous TNF-alpha exacerbates primary and secondary pulmonary
      histoplasmosis by differential mechanisms.
AB  - We investigated the mechanisms by which endogenous TNF-alpha modulates host
      defenses during experimental primary and secondary pulmonary infection with
      Histoplasma capsulatum (Hc). Neutralization of TNF-alpha in vivo resulted in
      increased CFU and 100% mortality in naive and immune mice challenged with Hc
      intranasally. Levels of IFN-gamma and granulocyte macrophage-CSF were elevated in
      TNF-alpha-neutralized naive mice, whereas IL-4, -6, -10 and TGF-beta did not
      differ from controls. In contrast, in secondary histoplasmosis, significant
      elevations of IL-4 and -10 were observed in TNF-alpha-depleted mice. Alveolar
      macrophages (Mphi) did not exert fungistatic activity against Hc after exposure
      to recombinant murine TNF-alpha, recombinant murine IFN-gamma, or both. The
      increase in susceptibility to primary Hc infection was associated with diminished
      production of reactive nitrogen intermediates by alveolar Mphi from TNF-alpha
      depleted mice, whereas production of nitric oxide during secondary histoplasmosis
      was similar in both groups. Upon secondary challenge, TNF-alpha-depleted mice
      were rescued by concomitant neutralization of IL-4 and IL-10, but not either
      cytokine alone. Thus, TNF-alpha is critical for controlling primary and secondary
      infection with Hc, and the mechanisms that lead mice to succumb to primary or
      secondary infection when endogenous TNF-alpha is blocked are different.

PMID- 9637525
TI  - Dissection of pathways leading to antigen receptor-induced and Fas/CD95-induced
      apoptosis in human B cells.
AB  - To dissect intracellular pathways involved in B cell Ag receptor (BCR)-mediated
      and Fas-induced human B cell death, we isolated clones of the Burkitt lymphoma
      cell line Ramos with different apoptosis sensitivities. Selection for sensitivity
      to Fas-induced apoptosis also selected for clones with enhanced BCR death
      sensitivity and vice versa. In contrast, clones resistant to Fas-mediated
      apoptosis could still undergo BCR-induced cell death. Based on the functional
      phenotypes of these clones, we hypothesized that both receptor-induced apoptosis
      pathways are initially distinct but may eventually converge. Indeed, ligation of
      both Fas and BCR resulted in cleavage of the IL-1beta-converting enzyme/Ced-3
      like protease caspase 3 and its substrates Ac-Asp-Glu-Val-Asp-aldehyde and
      poly(ADP-ribose) polymerase. Markedly, qualitative differences in the caspase 3
      cleavage pattern induced by Fas or BCR ligation were observed; whereas Fas
      ligation generated caspase 3 cleavage products of 19/20 and 17 kDa, only the
      latter cleavage product was found upon BCR cross-linking. The caspase inhibitor
      Val-Ala-Asp-fluoromethylketone blocked both Fas- and BCR-mediated apoptosis, but
      differentially affected caspase 3 cleavage induced by either stimulus. Finally,
      overexpression of a Fas-associated death domain (FADD) dominant-negative mutant
      protein was found to inhibit Fas-induced apoptosis but not BCR-induced apoptosis.
      Together our findings imply that Fas and BCR couple, via FADD-dependent and FADD
      independent mechanisms, respectively, to distinct proteases upstream of caspase
      3.

PMID- 9637526
TI  - T lymphocytes are required for protection of the vaginal mucosae and sensory
      ganglia of immune mice against reinfection with herpes simplex virus type 2.
AB  - Intravaginal inoculation of mice with an attenuated strain of herpes simplex
      virus type 2 (HSV-2) resulted in vigorous HSV-specific immune responses that
      protected against subsequent challenge with fully virulent HSV-2 strains. Even in
      the presence of high titers of HSV-specific Ab, T cell-dependent mechanisms were
      required for protection of the vaginal mucosae of HSV-immune mice and could be
      detected by 24 h after intravaginal reinoculation. Depletion of specific T cell
      subsets from HSV-immune mice before HSV-2 reinoculation demonstrated that CD4+ T
      cells were primarily responsible for this protection. Similarly, optimal
      protection of the sensory ganglia against reinfection with HSV-2 was dependent on
      the presence of T cells. Infectious HSV-2 was not detected in the sensory ganglia
      or spinal cord of HSV-immune mice depleted of only CD4+ or CD8+ T cells,
      suggesting that the T cell-mediated protection could be provided by either
      subset. Similarly, neutralization of IFN-gamma during challenge of HSV-immune
      mice resulted in diminished protection of the vaginal mucosa, but not of the
      sensory ganglia. These results suggest that the ability to induce vigorous HSV
      specific T cell responses is an important consideration in the design of vaccines
      to protect both the vaginal mucosa and sensory ganglia against HSV-2.

PMID- 9637527
TI  - Lack of both types 1 and 2 cytokines, tissue inflammatory responses, and immune
      protection during pulmonary infection by Mycobacterium bovis bacille Calmette
      Guerin in IL-12-deficient mice.
AB  - Understanding of key cytokines and the nature of protective immune responses in
      pulmonary mycobacterial diseases remains a task of paramount importance. In this
      study, both wild-type (wt) and IL-12-deficient (IL-12(-/-)) mice were infected by
      airways inoculation of live Mycobacterium bovis bacille Calmette-Guerin (BCG).
      The type 1 cytokines IL-12, IFN-gamma, and TNF-alpha, but not the type 2
      cytokines IL-4 and granulocyte macrophage (GM)-CSF, markedly increased in the
      lung and peripheral blood of wt mice postinfection, which resulted in the
      development of intense granulomatous responses and the effective control of
      mycobacterial infection in the lung. In contrast, IL-12(-/-) mice demonstrated a
      lack of both types 1 and 2 cytokines in the lung and blood and a severely
      impaired tissue immune-inflammatory response lacking not only macrophages and
      neutrophils but CD4 and CD8 T cells and NK cells in the lung throughout the
      entire course of study. Total lung mononuclear cells isolated from these mice, in
      contrast to wt mice, had an impaired recall immune response to Ag challenge in
      vitro. These impaired responses resulted in an uncontrolled local growth and
      systemic spread of bacilli. Our findings reveal that IL-12 plays an irreplaceable
      role in the initiation of Th1 responses, and the loss of its function cannot be
      compensated for by alternative mechanisms in the lung. This cytokine, together
      with IFN-gamma and TNF-alpha, and granulomatous inflammation are critically
      required for the effective control of pulmonary mycobacterial infection. Our
      results also indicate that the absence of type 1 cytokines does not necessarily
      favor a Th2 response.

PMID- 9637528
TI  - Altered intestinal immune system but normal antibacterial resistance in the
      absence of P-selectin and ICAM-1.
AB  - ICAM-1 and P-selectin are adhesion molecules that regulate leukocyte migration,
      extravasation to inflammatory sites, and other immune cell interactions. T cell
      mediated resistance against acute infection with Listeria monocytogenes and
      chronic infection with Mycobacterium bovis Calmette-Guerin bacillus was
      investigated in mutant mice lacking P-selectin and/or ICAM-1. Mice deficient in P
      selectin (Psel-/-), ICAM-1 (ICAM-/-), or the combination of both (Psel-/- x ICAM
      /-) showed normal bacterial clearance, comparable delayed-type hypersensitivity
      reactions, and equivalent memory T cell responses. Additionally, the distribution
      of alpahbeta vs gammadelta T lymphocyte populations was examined. Normal
      lymphocyte distributions were noted in thymus, spleen, and blood, whereas mutant
      mice showed marked alterations in the intestinal intraepithelial (i-IEL) and
      lamina propria lymphocytes. Differences in i-IEL populations were reflected
      functionally by differential lytic activities and cytokine productions of i-IEL
      populations from mutant mice. Despite these changes within the mucosal immune
      system of mutant mice, their resistance against oral infection with L.
      monocytogenes was apparently unimpaired. These findings demonstrate that P
      selectin and ICAM-1 are critically involved in the shaping of lymphocyte
      populations of the gut but have only a minor influence on systemic and regional
      host defense against intracellular bacteria.

PMID- 9637529
TI  - IL-4-dependent regulation of TGF-alpha and TGF-beta1 expression in human
      eosinophils.
AB  - TGFs play important roles in wound healing and carcinogenesis. We have previously
      demonstrated that eosinophils infiltrating into different pathologic processes
      elaborate TGF-alpha and TGF-beta1. Eosinophils infiltrating hamster cutaneous
      wounds were found to express TGFs sequentially. In this study, we examined the
      biologic mediators that may regulate the expression of TGF-alpha and -beta1 by
      eosinophils. Eosinophils were isolated from the peripheral blood of healthy
      donors and cultured in the absence or presence of IL-3, IL-4, and IL-5. Cells
      were analyzed by in situ hybridization and immunohistochemistry. Supernatants
      from these cultures were assayed for secreted TGF-alpha and TGF-beta1 using TGF
      specific ELISAs. IL-3, IL-4, and IL-5 independently up-regulated TGF-beta1 mRNA
      and product expression by eosinophils in all donors. Interestingly, TGF-alpha
      production by eosinophils was up-regulated by IL-3 and IL-5 but was down
      regulated by IL-4. Consistent with the ability of IL-4 to regulate eosinophil
      responses, IL-4 signaling molecules are present in human eosinophils. The
      observation that IL-4 can differentially regulate the expression of TGF-alpha and
      TGF-beta1 suggests that IL-4 may serve as a physiologic molecular switch of TGF
      expression by the infiltrating eosinophils in wound healing and carcinogenesis.

PMID- 9637530
TI  - Complement activation occurs on subendothelial extracellular matrix in vitro and
      is initiated by retraction or removal of overlying endothelial cells.
AB  - Vascular endothelium is continuously exposed to plasma complement, which could
      generate a potent proinflammatory signal if activated on the vascular wall.
      Normal endothelium, however, expresses an anti-inflammatory phenotype, which
      includes resistance to complement fixation. As activated endothelium converts to
      a proinflammatory phenotype, we investigated the effect of cytokines on
      endothelial susceptibility to complement fixation. Cytokine-treated HUVEC were
      exposed to human serum as a source of complement, and C3 deposition was
      quantified. IL-1beta and TNF-alpha in combination with IFN-gamma markedly
      increased endothelial C3 deposition; however, immunofluorescence microscopy
      revealed that the endothelial cells had retracted, and that bound C3 was
      concentrated not on cells but in areas of exposed subendothelial extracellular
      matrix (ECM). Studies with cell-free ECM indicated that complement activation
      required only ECM exposure and was independent of cellular activation. C3
      deposition on ECM was reproduced by reconstituting the alternative pathway, which
      generated a stable C3 convertase on ECM, but not on endothelial cells. C3b and
      iC3b were identified on ECM exposed to purified alternative pathway components
      and serum, respectively. In conditions associated with endothelial disruption,
      exposure of subendothelial ECM could induce complement fixation and contribute to
      inflammation and vascular damage.

PMID- 9637531
TI  - Immunization with purified natural and recombinant allergens induces mouse IgG1
      antibodies that recognize similar epitopes as human IgE and inhibit the human IgE
      allergen interaction and allergen-induced basophil degranulation.
AB  - Molecular characterization of allergens by recombinant DNA technology has made
      rapid progress in the recent few years. In the present study we immunized mice
      with aluminum hydroxide-adsorbed purified recombinant major timothy grass pollen
      allergens (rPhl p 1, rPhl p 2, rPhl p 5), dog albumin, a major animal dander
      allergen, and proteins with low (beta-lactoglobulin) or no (ribulose diphosphate
      carboxylase) allergenic potential in humans. Allergens that bind high levels of
      IgE in humans (Phl p 1, Phl p 5, dog albumin) induced high IgE and IgG1 levels in
      mice, whereas proteins with little or no allergenic activity in humans failed to
      induce significant IgE and IgG1 levels in mice. Continuous immunization for a
      period of 27 wk resulted in the production of mouse IgG1 Abs that recognized
      recombinant allergen fragments/epitopes defined by IgE Abs of allergic patients.
      As a consequence, allergen-specific mouse Abs strongly inhibited human IgE
      binding to the allergens and suppressed the allergen-induced histamine release
      from human basophils. In summary, our data indicate that 1) the allergenic
      potency of a protein may be related to its overall immunogenicity and 2)
      prolonged immunization with single purified recombinant allergens induces
      protective IgG Abs. The presented experimental in vivo/in vitro system allows the
      evaluation of Ag preparations (e.g., recombinant allergens) to be used for
      immunotherapy in humans.

PMID- 9637532
TI  - Arachidonic acid enhances the tissue factor expression of mononuclear cells by
      the cyclo-oxygenase-1 pathway: beneficial effect of n-3 fatty acids.
AB  - Monocytes express tissue factor (TF) upon stimulation by inflammatory agents.
      Dietary administration of fish oil rich in eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA) results in an impairment of TF expression by
      monocytes. EPA and DHA are metabolized differently from arachidonic acid (AA),
      the major fatty acid present in cell membranes. We examined the effects of AA on
      the TF expression of isolated human PBMC, and we determined whether EPA and DHA
      modulated this phenomenon differently. Nonstimulated PBMC had a low TF-dependent
      procoagulant activity. When PBMC were incubated with increasing concentrations of
      AA, the TF-dependent procoagulant activity increased in a dose-dependent manner
      to 190% at 7.5 microM. Indomethacin, a cyclo-oxygenase inhibitor, totally
      abolished the stimulating effect of AA, whereas specific pharmacologic inhibitors
      of cyclo-oxygenase-2 or of 5-lipoxygenase had no inhibitory effect. A thromboxane
      (TX)A2/endoperoxides receptor antagonist and a TX synthase inhibitor blocked the
      potentiating effect of AA. Purified PGG2 and carbocyclic TXA2, a TXA2 agonist,
      enhanced the procoagulant activity of PBMC in a dose-dependent manner whereas, in
      contrast, PGE2 inhibited it. Finally, contrary to AA, EPA or DHA did not increase
      TXB2 production or TF expression by PBMC. The TF-dependent procoagulant activity
      of isolated PBMC was increased by AA through the production of cyclo-oxygenase-1
      metabolites; the combined action of PGG2 and TXA2, which potentiated it, was
      greater than that of PGE2, which inhibited it. Dietary n-3 fatty acids exert part
      of their beneficial effect by modulating this procoagulant activity differently
      from AA.

PMID- 9637533
TI  - Complement receptor 3 of macrophages is associated with galectin-1-like protein.
AB  - We have previously identified a 16-kDa protein with a pI of 5.1 (P16/5.1) that is
      associated with macrophage CR3. Microsequencing of P16/5.1 indicated exclusive
      homology to the beta-galactoside-binding lectin, galectin-1. Abs specific to a
      galectin-1 unique peptide reacted with P16/5.1. The association of P16/5.1 with
      CR3 was specifically inhibited by lactose, which binds with high affinity to
      galectin-1. These data together with similarities in molecular mass and pI
      suggest that P16/5.1 is galectin-1. Two-color immunofluorescence staining
      revealed the expression of galectin-1 on the macrophage surface and its
      colocalization with CR3. However, a surplus of CR3 was free of galectin-1, and
      some galectin-1 molecules were associated with cell surface receptors other than
      CR3. Based on these results we propose two models depicting the functional
      significance of CR3-galectin-1 association: 1) homodimeric galectin-1 possessing
      a divalent sugar binding site may act as an extracellular adapter molecule that
      cross-links CR3 with other receptors; and 2) association of galectin-1 with beta
      galactosides on the extracellular domain of CR3 may modify the binding affinity
      of the receptor to its ligand. These possibilities are not mutually exclusive and
      can clarify the mode by which CR3 transmits signals in macrophages.

PMID- 9637534
TI  - Physiologic regulation of postovulatory neutrophil migration into vagina in mice
      by a C-X-C chemokine(s).
AB  - Leukocytes, particularly neutrophils, infiltrate into female genital organs after
      ovulation in both humans and mice. In mice, a female sexual cycle consists of 5
      phases: proestrus, estrus, metestrus-1, metestrus-2, and diestrus. Ovulation
      occurs at estrus; at metestrus-2, a large number of neutrophils infiltrate into
      the vaginal epithelium accompanied by an increased neutrophil number in vaginal
      lavage fluid. Concomitantly, concentrations of a functional IL-8 homologue,
      murine macrophage inflammatory protein (MIP)-2, were increased significantly in
      vaginal lavage fluid at metestrus-2 as compared with other phases. On the
      contrary, MIP-2 was not detected in plasma during the whole course of a sexual
      cycle. Moreover, immunohistochemical analyses demonstrated that MIP-2 protein
      expression was prominent at the upper layer of the vaginal epithelium at
      metestrus-2, in contrast to a marginal staining in the vaginal epithelium at
      proestrus and estrus. These results suggest that a C-X-C chemokine, MIP-2, was
      produced physiologically in the vaginal epithelium in a sexual cycle-dependent
      manner. Furthermore, the administration of neutralizing anti-IL-8R homologue Abs
      at proestrus abrogated leukocyte infiltration into the vagina at metestrus.
      However, anti-MIP-2 Abs reduced leukocyte influx at metestrus by approximately
      50%. Thus, a murine IL-8 homologue, MIP-2, and its related molecules
      physiologically regulate neutrophil migration into the vagina in a sexual cycle
      dependent manner.

PMID- 9637535
TI  - Novel role of transmembrane SCF for mast cell activation and eotaxin production
      in mast cell-fibroblast interactions.
AB  - Mast cell activation can be induced by multiple mechanisms, including IgE-,
      complement-, and stem cell factor (SCF)-mediated pathways. In addition, the
      interaction of mast cells with particular cell populations, such as fibroblasts,
      have also demonstrated increased mast cell reactivity. In these studies, we have
      investigated the role of fibroblast-mast cell interaction for induction of
      histamine release and chemokine production and the specific role of SCF during
      this interaction. Primary pulmonary fibroblast cell lines were grown in culture
      and used throughout these studies. Mast cells were grown in parallel with
      fibroblasts by incubation of bone marrow cells with SCF and IL-3. During mast
      cell-fibroblast coculture, increased histamine release could be attenuated either
      by separation of the cell populations using a Trans-Well setup, which did not
      allow cellular contact, or by specific anti-SCF Ab. In addition, a significant
      increase in eotaxin, a potent eosinophil-specific C-C chemokine, was also
      observed during fibroblast-mast cell interaction. The production of eotaxin was
      cell contact dependent and could be inhibited using an anti-SCF Ab or specific
      antisense therapy. SCF was constitutively produced from fibroblasts in its
      transmembrane form and could be induced by TNF. SCF-coated plates induced
      significant mast cell-derived eotaxin production, whereas soluble SCF induced
      little or no eotaxin, suggesting a necessity for receptor cross-linking for
      activation. These studies indicate that fibroblast-mast cell contact plays a role
      in exacerbation of histamine release and eotaxin production.

PMID- 9637536
TI  - Low grade rhinovirus infection induces a prolonged release of IL-8 in pulmonary
      epithelium.
AB  - Rhinoviruses are important respiratory pathogens implicated in asthma
      exacerbations. The mechanisms by which rhinoviruses trigger inflammatory
      responses in the lower airway are poorly understood, in particular their ability
      to infect the lower airway. Bronchial inflammatory cell (lymphocyte and
      eosinophil) recruitment has been demonstrated. IL-8 is a potent proinflammatory
      chemokine that is chemotactic for neutrophils, lymphocytes, eosinophils, and
      monocytes and may be important in the pathogenesis of virus-induced asthma.
      Increased levels of IL-8 have been found in nasal samples in natural and
      experimental rhinovirus infections. In these studies we therefore examine the
      ability of rhinovirus to infect a transformed lower airway epithelial cell line
      (A549) and to induce IL-8 protein release and mRNA induction. We observed that
      rhinovirus type 9 is able to undergo full viral replication in A549 cells, and
      peak viral titers were found 24 h after inoculation. Rhinovirus infection induced
      a dose- and time-dependent IL-8 release up to 5 days after infection and an
      increase in IL-8 mRNA expression that was maximal between 3 and 24 h after
      infection. UV inactivation of the virus completely inhibited replication, but
      only reduced IL-8 protein production and mRNA induction by half, while prevention
      of virus-receptor binding completely inhibited virus-induced IL-8 release,
      suggesting that part of the observed effects was due to viral replication and
      part was due to virus-receptor binding. These studies demonstrate that
      rhinoviruses are capable of infecting a pulmonary epithelial cell line and
      inducing IL-8 release. These findings may be important in understanding the
      pathogenesis of rhinovirus-induced asthma exacerbations.

PMID- 9637537
TI  - Role of TNFR1 and TNFR2 in TNF-induced platelet consumption in mice.
AB  - An injection of TNF in mice induced profound thrombocytopenia, due to an increase
      of platelet consumption, that was evident after 1 h and lasted for 3 days. This
      process was evident in mice that were genetically deficient in TNFR2 (p75) but
      not in mice lacking TNFR1 (p55), indicating that the process is mediated by TNFR1
      bearing cells. To explore the site of action of TNF, labeled platelets from TNFR1
      -/- or +/+ donors were transferred to TNFR1 -/- or +/+ recipients. TNF induced
      the consumption of platelets from TNFR1 -/- donors when injected into +/+
      recipients, while platelets from +/+ donors were not consumed when present in
      TNFR1 -/- recipients; this finding indicates that TNF acts on the TNFR1 of host
      cells but does not act on platelets. The expression of TNFRs is consistent with
      this interpretation, since TNFRs were not detected on platelets by flow
      cytometry. In megakaryocytes, the expression of TNFR1 was detected by
      immunohistochemistry. These results indicate that TNF induces platelet
      consumption by acting not on platelets directly but on the TNFR1 of other cells,
      presumably increasing the release of factors with agonist activity for platelets.

PMID- 9637538
TI  - An antigen recognized by autologous CTLs on a human bladder carcinoma.
AB  - By stimulating blood lymphocytes with autologous bladder carcinoma cells that had
      been transfected with B7-1, we obtained a panel of CTL clones which lyse
      specifically the bladder tumor cells in an MHC class I-restricted fashion. Based
      on inhibition with anti-HLA Abs and the recognition of allogeneic tumor cells, we
      could distribute our clones in three groups that recognized three distinct Ags.
      We characterized one of these Ags by screening a cDNA library prepared with the
      RNA from this bladder tumor line. This new tumor Ag is a peptide presented by HLA
      B4403 molecules. It is produced by a point mutation in a gene that is recorded in
      databases under the name KIAA0205, is ubiquitously expressed, and whose function
      is unknown. We also found this mutation in the tumor sample that was originally
      resected from this patient, but the mutation was not found in the 100 or more
      independent tumors of various histologic types that were tested. This report is
      the first to describe the isolation of CTL clones directed against human bladder
      cancer and the molecular characterization of a bladder tumor Ag.

PMID- 9637539
TI  - Antibody-IL-12 fusion proteins are effective in SCID mouse models of prostate and
      colon carcinoma metastases.
AB  - IL-12 is a complex cytokine in both its structure and its range of biologic
      activities. Fusions of this heterodimeric molecule with an intact antitumor Ab
      were made to test the feasibility and efficacy of targeting IL-12 to tumors to
      elicit a local immune response. Fusion proteins composed of the human p35 and p40
      subunits had IL-12 bioactivities that were nearly as potent on human immune cells
      as the rIL-12 standard, but were inactive on mouse cells. Hybrid IL-12 fusion
      proteins composed of mouse p35 and human p40, fused to Ab, were capable of
      inducing IFN-gamma, but were much less active on mouse spleen cells than a mouse
      IL-12 standard. Despite this relatively low activity, the hybrid fusion protein
      was as effective in a SCID mouse model as a fully active Ab-IL-2 fusion protein
      in eliminating established pulmonary metastases of CT26 colon carcinoma. Specific
      targeting of a human IL-12 fusion protein to metastatic prostate carcinoma
      xenografts was also shown to be effective in SCID mice transplanted with human
      lymphocyte-activated killer cells. These results demonstrate the importance of
      directing this potent cytokine to the tumor microenvironment and suggest an
      important alternative to systemic IL-12 administration or gene therapy for
      increasing its therapeutic index.

PMID- 9637540
TI  - Reconstitution of EBV-specific T cell immunity in solid organ transplant
      recipients.
AB  - EBV-specific autologous CTL were grown in vitro from three adults (two liver
      transplant recipients and one patient on hemodialysis awaiting kidney
      retransplant). All CTL lines were TCR alphabeta, CD8 positive cells, EBV
      specific, and MHC class I restricted. The CTL lines were expanded in vitro and
      infused in three escalating doses (5 x 10(7), 1 x 10(8), and 2 x 10(8) at monthly
      intervals. Weekly blood samples were collected following each infusion. EBV
      specific CTL precursor cells in peripheral blood were quantitated by limiting
      dilution analysis, and their effect on EBV load in vivo was assessed by
      semiquantitative PCR. In all three patients, the numbers of CTL precursor cells
      increased during the weeks following the infusions and were highest after the
      third infusion. This level gradually declined but remained above the preinfusion
      levels for up to 3 mo. EBV genome copy number, on the other hand, dropped
      following the first infusion and became undetectable thereafter. The EBV DNA
      level remained lower than the pretransplant level in all patients for up to 3 mo
      after the last infusion. Our study shows that it is feasible to generate and
      expand EBV-specific CTL from pretransplant blood samples of solid organ
      transplant recipients, that these CTL can be stored and infused posttransplant,
      and that they remain cytotoxic and EBV specific in vivo. The aim of this study is
      to use these CTL for prevention and treatment of lymphoproliferative disease in
      solid organ transplant recipients.

PMID- 9637541
TI  - Transfection of the type II TGF-beta receptor into colon cancer cells increases
      receptor expression, inhibits cell growth, and reduces the malignant phenotype.
AB  - OBJECTIVE: To determine if transfection of SW48 colon cancer cells with the type
      II transforming growth factor-beta (TGF-beta) receptor restores growth inhibition
      and reverses the in vitro and in vivo malignant phenotype. SUMMARY BACKGROUND
      DATA: The authors have previously shown that SW48 colon cancer cells that are
      replication error positive in both alleles lack functional cell surface TGF-beta
      type I (RI) and type II (RII) receptors and are insensitive to TGF-beta1-induced
      growth inhibition. METHODS: SW48 cells were stably transfected with the cDNA for
      the normal type II TGF-beta receptor (RII). Once transfected, the cells were
      evaluated for in vitro phenotypic changes and in vivo changes in tumor growth.
      RESULTS: Denaturing sequencing gel electrophoresis of the reverse transcriptase
      polymerase chain reaction product from SW48 cells revealed that the RII coding
      sequence contained a single base deletion mutation. When these cells were
      transfected with normal RII cDNA, Northern and Western blot analyses revealed
      increased levels of RII mRNA and protein. Affinity labeling techniques revealed
      that RII-transfected SW48 cells produced functional RI and RII protein.
      Transfection of SW48 cells also led to changes in cell phenotype, as shown by
      inhibition of both in vitro growth rate and incorporation of [3H]-thymidine. SW48
      cells expressing normal RII also exhibited reduced cloning efficiency in
      semisolid medium and reduced growth as a xenograft in NOD/LtSz-scid/J mice.
      CONCLUSIONS: The results confirm that RII is a tumor-suppressor protein that is
      required for TGF-beta-induced growth inhibition in SW48 colon cancer cells.

PMID- 9637542
TI  - Testosterone: the crucial hormone responsible for depressing myocardial function
      in males after trauma-hemorrhage.
AB  - OBJECTIVE: To determine whether testosterone depletion in males before trauma
      hemorrhage has any salutary effects on cardiac performance after hemorrhage and
      resuscitation. SUMMARY BACKGROUND DATA: Studies indicate that castration of male
      mice before trauma-hemorrhage prevents the immunodepression seen after hemorrhage
      and resuscitation. However, the effect of precastration on cardiac performance
      under such conditions remains unknown. METHODS: Male rats were castrated or sham
      castrated 14 days before the experiment. After laparotomy (i.e., induction of
      trauma), the rats were bled to and maintained at a mean arterial pressure of 40
      mm Hg until 40% of the maximal shed volume was returned in the form of Ringer's
      lactate solution. The animals were then resuscitated with four times the shed
      blood volume with Ringer's lactate solution over 60 minutes. Heart performance
      was measured using a left ventricular catheter connected to an in vivo heart
      performance analyzer. Indices of left ventricular performance (i.e., maximal rate
      of the pressure increase [+dP/dt(max)] and decrease [-dP/dt(max)) were measured
      up to 4 hours after trauma, hemorrhagic shock, and resuscitation. RESULTS: In
      sham-castrated animals, trauma-hemorrhage and resuscitation decreased the in vivo
      heart performance as evidenced by the reduced values of +dP/dt(max) and 
      dP/dt(max). Precastrated animals, however, showed significantly higher values of
      +dP/dt(max) and -dP/dt(max) than sham-castrated animals after trauma-hemorrhage
      and resuscitation. CONCLUSIONS: Testosterone antagonism in males might be an
      effective approach for maintaining myocardial function after adverse circulatory
      conditions. Although testosterone depletion in male trauma victims is neither
      practical nor advocated, testosterone receptor blockade after trauma may
      represent a novel and useful adjunct for maintaining normal myocardial
      performance under those conditions.

PMID- 9637543
TI  - Surgical treatment of adenocarcinoma of the rectum.
AB  - OBJECTIVE: The authors' aim was to determine survival and recurrence rates in
      patients undergoing resection of rectal cancer achieved by abdominoperineal
      resection (APR), coloanal anastomosis (CAA), and anterior resection (AR) without
      adjuvant therapy. SUMMARY BACKGROUND DATA: The surgery of rectal cancer is
      controversial; so, too, is its adjuvant management. Questions such as
      preoperative versus postoperative radiation versus no radiation are key. An
      approach in which the entire mesorectum is excised has been proposed as yielding
      low recurrence rates. METHODS: Of 1423 patients with resected rectal cancers, 491
      patients were excluded, leaving 932 with a primary adenocarcinoma of the rectum
      treated at Mayo. Eighty-six percent were resected for cure. Surgery plus adjuvant
      treatment was performed in 418, surgery alone in 514. These 514 patients are the
      subject of this review. Among the 514 patients who underwent surgery alone, APR
      was performed in 169, CAA in 19, AR in 272, and other procedures in 54. Eighty
      seven percent of patients were operated on with curative intent. The mean follow
      up was 5.6 years; follow-up was complete in 92%. APR and CAA were performed
      excising the envelope of rectal mesentery posteriorly and the supporting tissues
      laterally from the sacral promontory to the pelvic floor. AR was performed using
      an appropriately wide rectal mesentery resection technique if the tumor was high;
      if the tumor was in the middle or low rectum, all mesentery was resected. The
      mean distal margin achieved by AR was 3 +/- 2 cm. RESULTS: Mortality was 2% (12
      of 514). Anastomotic leaks after AR occurred in 5% (16 of 291) and overall
      transient urinary retention in 15%. Eleven percent of patients had a wound
      infection (abdominal and perineal wound, 30-day, purulence, or cellulitis). The
      local recurrence and 5-year disease-free survival rates were 7% and 78%,
      respectively, after AR; 6% and 83%, respectively, after CAA; and 4% and 80%,
      respectively, after APR. Patients with stage III disease, had a 60% disease-free
      survival rate. CONCLUSIONS: Complete resection of the envelope of supporting
      tissues about the rectum during APR, CAA, and AR when tumors were low in the
      rectum is associated with low mortality, low morbidity, low local recurrence, and
      good 5-year survival rates. Appropriate "tumor-specific" mesorectal excision
      during AR when the tumor is high in the rectum is likewise consistent with a low
      rate of local recurrence and good long-term survival. However, the overall
      failure rate of 40% in stage III disease (which is independent of surgical
      technique) means that surgical approaches alone are not sufficient to achieve
      better long-term survival rates.

PMID- 9637544
TI  - Transient human gene therapy: a novel cytokine regulatory strategy for
      experimental pancreatitis.
AB  - OBJECTIVE: The purpose of this study was to evaluate the ability to transfect a
      murine pancreas with a human cytokine regulatory gene (interleukin-10 [IL-10])
      and examine the duration of transgene expression, its effect on the normal
      pancreas, and its antiinflammatory effect during acute pancreatitis. SUMMARY
      BACKGROUND DATA: Interleukin-1beta and tumor necrosis factor-alpha are known
      detrimental mediators during the progression of acute pancreatitis, and blockade
      of either cytokine results in decreased severity of pancreatitis and improved
      survival. Although gene therapy has been proposed as a method to deliver protein
      based therapy during a number of conditions, no means of effectively transfecting
      the pancreas without inducing injury has been developed. METHODS: A plasmid-human
      IL-10 construct (pMP6-hIL-10) complexed with cationic liposomes was administered
      by single intraperitoneal injection to healthy mice. Effective transfection
      (reverse transcriptase-polymerase chain reaction for hIL-10 mRNA), transfected
      cell type (in situ polymerase chain reaction for hIL-10 DNA), and the effect on
      the normal pancreas were determined. Additional animals were transfected to
      determine the effects of this regulatory gene on the severity of pancreatitis.
      RESULTS: Nearly 80% of all pancreatic cells expressed human DNA that was
      subsequently transcribed into mRNA through day 14. The transfection event had no
      effect on amylase, lipase, or pancreatic histologic appearance. Successful
      transfection could attenuate subsequently induced pancreatitis (all parameters p
      < 0.05). CONCLUSIONS: Transient transfection of a human IL-10 gene can be
      accomplished into all cell types of murine pancreata using a plasmid/ liposome
      vector. The DNA is effectively transcribed into intact mRNA and does not cause
      inflammation or acinar cell damage. Transfer of this cytokine regulatory gene
      decreases the severity of pancreatitis, demonstrating a benefit of gene therapy
      during this acute inflammatory process.

PMID- 9637545
TI  - Periampullary adenocarcinoma: analysis of 5-year survivors.
AB  - OBJECTIVE: This single-institution experience retrospectively reviews the
      outcomes in a group of patients treated 5 or more years ago by
      pancreaticoduodenectomy for periampullary adenocarcinoma. SUMMARY BACKGROUND
      DATA: Controversy exists regarding the benefit of resection for periampullary
      adenocarcinoma, particularly for pancreatic tumors. Many series report only
      Kaplan-Meier actuarial 5-year survival rates. There are believed to be
      discrepancies between the actuarial 5-year survival data and the actual 5-year
      survival rates. METHODS: From April 1970 through May 1992, 242 patients underwent
      pancreaticoduodenal resection for periampullary adenocarcinoma at The Johns
      Hopkins Hospital. Follow-up was complete through May 1997. All pathology
      specimens were reviewed and categorized. Actual 5-year survival rates were
      calculated. The demographic, intraoperative, pathologic, and postoperative
      features of patients surviving > or =5 years were compared with those of patients
      who survived <5 years. RESULTS: Of the 242 patients with resected periampullary
      adenocarcinoma, 149 (62%) were pancreatic primaries, 46 (19%) arose in the
      ampulla, 30 (12%) were distal bile duct cancers, and 17 (7%) were duodenal
      cancers. There was a 5.3% operative mortality rate during the 22 years of the
      review, with a 2% operative mortality rate in the last 100 patients. There were
      58 5-year survivors, 28 7-year survivors, and 7 10-year survivors. The tumor
      specific 5-year actual survival rates were pancreatic 15%, ampullary 39%, distal
      bile duct 27%, and duodenal 59%. When compared with patients who did not survive
      5 years, the 5-year survivors had a significantly higher percentage of well
      differentiated tumors (14% vs. 4%; p = 0.02) and higher incidences of negative
      resection margins (98% vs. 73%, p < 0.0001) and negative nodal status (62% vs.
      31%, p < 0.0001). The tumor-specific 10-year actuarial survival rates were
      pancreatic 5%, ampullary 25%, distal bile duct 21%, and duodenal 59%.
      CONCLUSIONS: Among patients with periampullary adenocarcinoma treated by
      pancreaticoduodenectomy, those with duodenal adenocarcinoma are most likely to
      survive long term. Five-year survival is less likely for patients with ampullary,
      distal bile duct, and pancreatic primaries, in declining order. Resection margin
      status, resected lymph node status, and degree of tumor differentiation also
      significantly influence long-term outcome. Particularly for patients with
      pancreatic adenocarcinoma, 5-year survival is not equated with cure, because many
      patients die of recurrent disease >5 years after resection.

PMID- 9637546
TI  - Reduction of hepatic ischemia/reperfusion injury by a soluble P-selectin
      glycoprotein ligand-1.
AB  - OBJECTIVE: The authors' goal was to determine the effects of specific binding and
      blockade of P- and E-selectins by a soluble P-selectin glycoprotein ligand-1
      (PSGL-1) in rat models of hepatic in vivo warm ischemia and ex vivo cold
      ischemia. The authors also sought to determine the effect of selectin blockade on
      isograft survival in a syngeneic rat orthotopic liver transplant model. SUMMARY
      BACKGROUND DATA: Ischemia/reperfusion (I/R) injury is a major factor in poor
      graft function after liver transplantation, which may profoundly influence early
      graft function and late changes. It is hypothesized that I/R injury leads to the
      upregulation of P-selectin, which is then rapidly translocated to endothelial
      cell surfaces within 5 minutes of reperfusion of the liver, initiating steps
      leading to tethering of polymorphonuclear neutrophil leukocytes to the vascular
      intima. Local production by leukocytes of interleukin-1, tumor necrosis factor
      alpha, or both induces P-selectin expression on the endothelium and continues the
      cascade of events, which increases cell adherence and infiltration of the organ.
      METHODS: To examine directly the effects of selectins in a warm hepatic I/R
      injury model, 100 microg of PSGL-1 or saline was given through the portal vein at
      the time of total hepatic inflow occlusion. The effects of PSGL-1 in cold
      ischemia were assessed using an isolated perfused rat liver after 6 hours of 4
      degrees C storage in University of Wisconsin (UW) solution, with or without the
      instillation of PSGL-1 before the storage. To evaluate the effect of selectin
      blockade on liver transplant survival, syngeneic orthotopic liver transplants
      were performed between inbred male Sprague-Dawley rats after 24 hours of cold
      ischemic storage in UW solution. A separate group of animals received two doses
      of 100 microg of PSGL-1 through the portal vein before storage and before
      reperfusion of the transplanted liver. Recipient survival was assessed at 7 days,
      and the Kaplan-Meier product limit estimate method was used for univariate
      calculations of time-dependent recipient survival events. RESULTS: In an in vivo
      warm rat liver ischemia model, perfusion with PSGL-1 afforded considerable
      protection from I/R injury, as demonstrated by decreased transaminase release,
      reduced histologic hepatocyte damage, and suppressed neutrophil infiltration,
      versus controls (p < 0.05). When cold stored livers were reperfused, PSGL-1
      reduced the degree of hepatocyte transaminase release, reduced neutrophil
      infiltration, and decreased histologic hepatocyte damage (p < 0.05 vs. UW-only
      controls). On reperfusion, livers treated with PSGL-1 demonstrated increased
      portal vein blood flow and bile production (p < 0.05 vs. UW-only controls). In
      addition, 90% of the rats receiving liver isografts stored in UW solution
      supplemented with PSGL-1 survived 7 days versus 50% of those whose transplanted
      syngeneic livers had been stored in UW alone (p < 0.05). CONCLUSIONS: Selectins
      play an important role in I/R injury of the liver. Early modulation of the
      interaction between P-selectin and its ligand decreases hepatocyte injury,
      neutrophil adhesion, and subsequent migration in both warm and cold rat liver
      ischemia models. In addition, the use of PSGL-1 before ischemic storage and
      before transplantation prevents hepatic injury, as documented by a significant
      increase in liver isograft survival. These findings have important clinical
      ramifications: early inhibition of alloantigen-independent mechanisms during the
      I/R damage may influence both short- and long-term survival of liver allografts.

PMID- 9637547
TI  - Improved clinical outcomes with liver transplantation for hepatitis B-induced
      chronic liver failure using passive immunization.
AB  - OBJECTIVE: The goals were to summarize the results of liver transplantation for
      chronic hepatitis B disease (HBV) at the University of Virginia, correlate
      pretransplant viral markers with posttransplant hepatitis B immunoglobulin (HBIg)
      requirements, and identify the relation between viral protein in the liver and
      clinical reinfection. SUMMARY BACKGROUND DATA: Liver transplantation is an
      accepted treatment for end-stage liver disease from chronic HBV infection,
      although lifelong antiviral treatment (with HBIg or antiviral agents) is still
      necessary. Patients with evidence of active viral replication (detectable serum
      HBV-DNA or e antigen) at the time of transplant have a higher rate of allograft
      infection. Whether clinically stable patients receiving HBIg immunoprophylaxis
      have detectable viral products in their grafts remains unknown. METHODS: Forty
      four transplants performed for HBV disease at the University of Virginia since
      March 1990 were reviewed. Most patients underwent aggressive passive
      immunoprophylaxis with HBIg to maintain serum HBV surface antibody (HBsAb) levels
      > or =500 IU/l for the first 6 months after the transplant, and > or =150 IU/l
      thereafter. Patients had viral markers quantified, underwent pharmacokinetic
      analysis of HBsAb levels to adjust dosing, and were biopsied routinely every 3 to
      6 months and when indicated. RESULTS: Forty-four transplants were performed in 39
      patients. Actual 1-year and 3-year graft survival was 95% and 81%, respectively,
      and 1-year and 3-year patient survival was 98% and 96%, respectively. After the
      adoption of indefinite HBIg prophylaxis, nine grafts became infected (all in
      recipients positive for HBV e antigen). Three occurred within 8 weeks of
      transplantation and were associated with a short HBsAb half-life and a wild-type
      virus. Six occurred >8 months after the transplant, and most of these were
      associated with viral mutation. Quantification of pretransplant markers was an
      overall poor predictor of HBIg requirements after the transplant.
      Immunohistochemistry demonstrated transient low-level expression of core protein
      in the liver in 23% of patients without serum or clinical evidence of recurrent
      hepatitis. CONCLUSIONS: An excellent outcome is possible after liver
      transplantation for chronic HBV disease using HBIg dosed by pharmacokinetic
      parameters. Currently, quantification of pretransplant serum markers of the HBV
      antigen load does not predict the intensity of posttransplant treatment required
      for good clinical outcomes. Because HBV is not eradicated from the patient, some
      form of indefinite antiviral therapy continues to be warranted.

PMID- 9637548
TI  - Microvascular changes explain the "two-hit" theory of multiple organ failure.
AB  - OBJECTIVE: The objective was to determine intestinal microvascular endothelial
      cell control after sequential hemorrhage and bacteremia. SUMMARY BACKGROUND DATA:
      Sepsis that follows severe hemorrhagic shock often results in multiple system
      organ failure (MSOF) and death. The sequential nature of this clinical scenario
      has led to the idea of a "two-hit" theory for the development of MSOF, the
      hallmark of which is peripheral vasodilation and acidosis. Acute bacteremia alone
      results in persistent intestinal vasoconstriction and mucosal hypoperfusion.
      Little experimental data exist to support the pathogenesis of vascular
      dysregulation during sequential physiologic insults. We postulate that
      hemorrhagic shock followed by bacteremia results in altered microvascular
      endothelial cell control of dilation and blood flow. METHODS: Rats underwent
      volume hemorrhage and resuscitation. A sham group underwent the vascular
      cannulation without hemorrhage and resuscitation, and controls had no surgical
      manipulation. After 24 and 72 hours, the small intestine microcirculation was
      visualized by in vivo videomicroscopy. Mean arterial pressure, heart rate,
      arteriolar diameters, and A1 flow by Doppler velocimetry were measured.
      Endothelial-dependent dilator function was determined by the topical application
      of acetylcholine (ACh). After 1 hour of Escherichia coil bacteremia, ACh dose
      responses were again measured. Topical nitroprusside was then applied to assess
      direct smooth muscle dilation (endothelial-independent dilator function) in all
      groups. Vascular reactivity to ACh was compared among the groups. RESULTS: Acute
      bacteremia, with or without prior hemorrhage, caused significant large-caliber A1
      arteriolar constriction with a concomitant decrease in blood flow. This
      constriction was blunted at 24 hours after hemorrhage but was restored to control
      values by 72 hours. There was a reversal of the response to bacteremia in the
      premucosal A3 vessels, with a marked dilation both at 24 and 72 hours. The
      sequence of hemorrhage and E. coli resulted in a progressive enhanced reactivity
      to the endothelial-dependent stimulus of ACh in the A3 vessels at 24 and 72
      hours. Reactivity to endothelial-independent smooth muscle relaxation and
      subsequent vessel dilation was similar for all groups. CONCLUSIONS: These data
      indicate that there is altered endothelial control of the intestinal
      microvasculature after hemorrhage in favor of enhanced dilator mechanisms in
      premucosal vessels with enhanced constrictor forces in inflow vessels. This
      enhanced dilator sensitivity is most evident in small premucosal vessels. This
      experimental finding supports the premise that an initial pathophysiologic stress
      alters the subsequent microvascular blood flow responses to systemic
      inflammation. These changes in the intestinal microcirculation are in concert
      with the "two-hit" theory for MSOF.

PMID- 9637549
TI  - Diagnosis and initial management of blunt pancreatic trauma: guidelines from a
      multiinstitutional review.
AB  - OBJECTIVE: The authors' objective was to resolve the current controversies
      surrounding the diagnosis and management of blunt pancreatic trauma (BPT).
      SUMMARY BACKGROUND DATA: The diagnosis of BPT is notoriously difficult: serum
      amylase has been claimed to be neither sensitive nor specific, and recent
      anecdotal reports have suggested a role for computed tomography. The therapy of
      BPT has been controversial, with some suggesting selective observation and others
      advocating immediate exploration to prevent a delay-induced escalation in
      morbidity and death. METHODS: The authors conducted a retrospective chart review
      of documented BPT from six institutions, using a standardized binary data form
      composed of 187 items and 237 data fields. RESULTS: A significant correlation
      between pancreas-specific morbidity and injury to the main pancreatic duct (MPD)
      was noted. Patients requiring delayed surgical intervention after an unsuccessful
      period of observation demonstrated notably higher pancreas-specific mortality and
      morbidity rates, principally because of the incidence of unrecognized injuries to
      the MPD. Although detection of MPD injuries by computed tomography was no better
      than flipping a coin, endoscopic pancreatography was accurate in each of the five
      cases in which it was used. CONCLUSIONS: The principal cause of pancreas-specific
      morbidity after BPT is injury to the MPD. Parenchymal pancreatic injuries not
      involving the ductal system rarely result in pancreas-specific morbidity or
      death. Delay in recognizing MPD injury leads to increased mortality and morbidity
      rates. CT is unreliable in diagnosing MPD injury and should not be used to guide
      therapy. Initial selection of patients with isolated BPT for observation or
      surgery can be based on the determination of MPD integrity.

PMID- 9637550
TI  - Pancreatic necrosis: results of necrosectomy, packing, and ultimate closure over
      drains.
AB  - OBJECTIVE: The treatment of pancreatic necrosis at a tertiary referral center was
      reviewed to effect better patient outcome. SUMMARY BACKGROUND DATA: Pancreatic
      necrosis is a devastating disease that leads to death in 10% to 50% of cases.
      Infected necrosis is particularly deadly because 80% of deaths from necrosis are
      due to infection or its complications. Therapeutic strategies center on
      aggressive support of organ systems and prevention and treatment of infectious
      complications. METHODS: Records of all patients who underwent pancreatic
      necrosectomy from 1990 to 1996 at Emory University Hospital were reviewed.
      Patients with infected necrosis were debrided as soon as the diagnosis was made.
      Reoperation for completion necrosectomy with ultimate closure over lavage
      catheters was performed as necessary. RESULTS: Of the 244 patients admitted with
      acute pancreatitis in the study period, 50 underwent pancreatic debridement. The
      mean age was 52 years, and 74% of patients were transferred from other
      institutions. Eighty-four percent of patients had infected necrosis, and all
      patients underwent sequential debridement with eventual closure over drains.
      Organ failure occurred in 72% of cases, and the overall mortality rate was 12%.
      The mean length of stay was 54 days. CONCLUSIONS: The management of pancreatic
      necrosis demands the allocation of extensive resources. An aggressive operative
      strategy of multiple debridements with ultimate closure over drains can lead to a
      low mortality rate in patients with this complex disease, but the determination
      of when to explore patients with sterile necrosis remains difficult.

PMID- 9637551
TI  - Operative treatment of tertiary hyperparathyroidism: a single-center experience.
AB  - OBJECTIVE: To review the experience with the operative treatment of tertiary
      hyperparathyroidism (TH) from a single renal transplant center. SUMMARY
      BACKGROUND DATA: Most patients with chronic renal failure show evidence of
      secondary hyperparathyroidism by the time maintenance hemodialysis begins.
      Persistent secondary hyperparathyroidism (i.e., TH) requiring surgical
      intervention is uncommon in the authors' experience. METHODS: Charts of patients
      who underwent parathyroidectomy for TH were reviewed retrospectively. Information
      obtained included demographics, laboratory data, symptoms, operative procedure
      (including morbidity and mortality rates), and pathology. Comparisons of
      demographic data and allograft survival were made between the transplant
      population as a whole and a matched cohort group of patients. RESULTS: Thirty
      eight patients from 4344 renal transplant procedures during a 29-year period
      required parathyroidectomy for TH. All patients had hypercalcemia; 20 were
      asymptomatic and 18 had varying symptoms. Mean time from renal transplantation to
      parathyroidectomy was 997 +/- 184 days, with a mean preoperative calcium level of
      12.2 +/- 0.14 mg/dl. Total parathyroidectomy with parathyroid autograft was
      performed in 26 of 34 primary procedures. There were no deaths. The operative
      morbidity rate was 6% (wound separation and vocal cord hemiparesis, one each).
      Pathology was reported in all patients and recently reviewed in 28 patients.
      Twenty-four had diffuse hyperplasia and nine had nodular hyperplasia; one had an
      adenoma. Parathyroid glands diagnosed as nodular hyperplasia were significantly
      larger by total mass than those with diffuse hyperplasia. Comparison of allograft
      survival between the study group and a matched cohort group of patients revealed
      no difference in long-term graft survival. CONCLUSIONS: Operative intervention is
      recommended in patients with an asymptomatic increase in serum calcium to >12.0
      mg/dl persisting for >1 year after the transplant, acute hypercalcemia (calcium
      >12.5 mg/dl) in the immediate posttransplant period, and symptomatic
      hypercalcemia.

PMID- 9637552
TI  - Effective long-term palliation of symptomatic, incurable metastatic medullary
      thyroid cancer by operative resection.
AB  - OBJECTIVE: To evaluate the short- and long-term consequences of palliative
      reresection of specific symptomatic lesions in patients with widely disseminated
      (incurable) medullary thyroid cancer (MTC). SUMMARY BACKGROUND DATA: Although
      reoperative neck microdissections can normalize calcitonin levels in patients
      with metastatic MTC confined to regional lymph nodes, there is no curative
      therapy for widely metastatic disease. However, these patients frequently have
      prolonged survival, but often with debilitating symptoms. METHODS: Between
      October 1981 and January 1997, 16 patients (mean age, 46 +/- 3 years; 10/16
      female) underwent 21 palliative reoperations for unresectable MTC at the Johns
      Hopkins Hospital. All patients had significant symptom(s) or impending compromise
      of vital structures by a discrete lesion and had unequivocal preoperative
      evidence of a total disease burden that was unresectable. RESULTS: The mean
      interval from initial thyroidectomy to palliative surgery was 5.8 +/- 1.5 years.
      All patients had significant tumor burdens as evidenced by preoperative
      calcitonin values ranging from 900 to 222,500 pg/mL (nL < or = 17 pg/mL). The
      palliative operations consisted of reoperative neck dissection/mass excision
      (11), mediastinal mass resection (4), esophagectomy (1), liver trisegmentectomy
      (1), sigmoidectomy (1), bilateral simple mastectomies (1), pituitary resection
      (1), and subcutaneous mass excisions (1). All but two of the operative specimens
      contained MTC. There was no perioperative mortality. The long-term morbidity rate
      was limited to one recurrent laryngeal nerve injury. All patients had initial
      relief of the index symptom(s) after the palliative surgery, followed by a median
      actuarial symptom-free survival rate of 8.2 years. CONCLUSIONS: Patients with
      widely metastatic MTC often live for years, but many develop symptoms secondary
      to tumor persistence or progression. Judicious palliative, reoperative resection
      of discrete, symptomatic lesions can provide significant long-term relief of
      symptoms with minimal operative mortality and morbidity. In selected patients
      with metastatic MTC lesions causing significant symptoms or physical compromise,
      palliative reoperative resection should be considered despite the presence of
      widespread incurable metastatic disease.

PMID- 9637553
TI  - Cystadenomas of the pancreas: is enucleation an adequate operation?
AB  - OBJECTIVE: The objective was to determine whether surgical enucleation of
      mucinous cystadenoma of the pancreas is a safe and adequate operation. SUMMARY
      BACKGROUND DATA: Mucinous cystadenomas of the pancreas are premalignant cystic
      lesions. Resection is the preferred treatment but often requires a
      pancreatoduodenectomy or a distal pancreatectomy with or without a splenectomy.
      Although these procedures can now be performed with a low mortality rate,
      substantial morbidity still occurs, especially in patients who have an otherwise
      normal pancreas. METHODS: Between January 1990 and June 1997, 36 mucinous
      cystadenomas of the pancreas were resected at The Johns Hopkins Hospital. Most of
      these patients underwent pancreatoduodenectomy or distal pancreatectomy. However,
      10 patients (28%) underwent enucleation of their cystic tumor. These 10 patients
      had a mean age of 63 years, and 6 were men. The cystic lesion was demonstrated by
      computed tomography in all patients. Enucleation of the cyst was performed in
      each patient, and four underwent another concomitant abdominal procedure. These
      10 patients were followed with periodic computed tomographic scans and clinical
      examinations. RESULTS: Enucleation took less time and was associated with less
      blood loss than resection. Pancreatic fistulas occurred more frequently after
      enucleation, but the incidence of major complications was similar between the two
      groups. Follow-up after enucleation averaged 43 months, and none of the patients
      developed late sequelae or recurrence. CONCLUSIONS: This experience suggests that
      enucleation of mucinous cystadenomas of the pancreas can be performed safely and
      that the recurrence rate is low after this procedure. The authors conclude that
      enucleation is an adequate procedure for benign cystic neoplasms of the pancreas.

PMID- 9637554
TI  - Acute pancreatitis induces cytokine production in endotoxin-resistant mice.
AB  - OBJECTIVE: The purpose of this study was to determine whether pathologic
      progression and cytokine responses in acute pancreatitis (AP) are altered in the
      absence of endotoxemia. SUMMARY BACKGROUND DATA: Previous studies have
      demonstrated that AP is characterized by rapid production and release of
      inflammatory cytokines, which play a major role in the local pancreatic and
      systemic complications of this disease. Infection and endotoxemia have been
      implicated as a major source of morbidity and death in AP and as possible stimuli
      for the overwhelming cytokine response seen in this disease. METHODS: AP was
      induced by a choline-deficient and ethionine-supplemented diet for 4 days in
      normal C57BL/6J mice (controls, n = 23) and in CD14 knockout mice (CD14KO, n =
      23), which cannot produce circulating cytokines in response to endotoxin. Control
      and endotoxin-resistant mice were killed at time 0, then at 24, 48, 72, and 96
      hours after the start of the diet. At each time point serum was collected for
      amylase, glucose, and cytokine measurements (tumor necrosis factor-alpha
      [TNFalpha] and interleukin-1beta [IL1beta]), and the pancreas was removed for
      histologic examination. TNFalpha was measured with a bioassay using WEHI-2F cells
      and IL1beta with a bioassay using D10.G4.1 cells. RESULTS: CD14KO mice developed
      biochemical manifestations of AP with alterations in amylase levels,
      hypoglycemia, weight loss, and histologic changes of pancreatitis similar to the
      pattern seen in control mice. TNFalpha and IL1beta production had similar
      kinetics in both groups, with significant peak TNFalpha serum levels at 72 hours
      and a progressive rise of IL1beta levels throughout the study period. Histologic
      changes appeared earlier and were more pronounced in the control versus the
      CD14KO mice. However, the mortality rate was identical (20% at 96 hours) for both
      groups. CONCLUSIONS: These results demonstrate that the progression of AP, the
      cytokine response associated with the disease, and early death are independent of
      endotoxin action. These findings, which suggest that an uncharacterized stimulus
      is responsible for triggering the cytokine cascade in this disease, may have
      significant implications for the management of patients with AP.

PMID- 9637555
TI  - Total thyroidectomy does not enhance disease control or survival even in high
      risk patients with differentiated thyroid cancer.
AB  - SUMMARY BACKGROUND DATA: The extent of primary thyroidectomy for differentiated
      thyroid cancer is controversial. There are strong proponents for total
      thyroidectomy based on its presumed and theoretical disease control benefits. In
      contrast, there are equally strong advocates of less aggressive thyroidectomy
      with its lower hazard of parathyroid and recurrent nerve injury. The authors have
      addressed whether total thyroidectomy has a survival benefit justifying its use
      in patients with high-risk primary cancer. The major risk factors include age and
      the following the pathologic determinants follicular histology, vascular
      invasion, and extracapsular extension. MATERIALS AND METHODS: The clinical
      pathologic, therapeutic, prognostic, and outcome data were reviewed in 347
      patients with well-differentiated thyroid cancer. Seventy-five percent were
      women, 216 patients were in the younger age group (low-risk) (21-50 years), 103
      were in the intermediate-risk group (51-70 years), and 28 were in the high-risk
      group (>70 years). Included in the high-risk pathologic category were 158
      patients who had follicular histology (55), extracapsular extension (107), or
      vascular invasion (119). Total thyroidectomy was performed in 56 patients, near
      or subtotal thyroidectomy in 47 patients and lobectomy in 55 patients. The 10
      year disease specific survival in the overall patient group was 82% in patients
      with total thyroidectomy, 78% in patients with subtotal thyroidectomy, and 89% in
      patients with lobectomy (p = 0.30). There was no significant survival difference
      according to extent of thyroidectomy in the intermediate or high-risk groups
      either by age or in patients who had high-risk pathologic feature. CONCLUSIONS:
      Total thyroidectomy in high-risk patients with differentiated thyroid cancer
      (containing follicular histology, vascular invasion, or extracapsular extension)
      showed no benefit over partial thyroidectomy. This suggests that the general use
      of total thyroidectomy is not indicated, except in highly selected patients.

PMID- 9637557
TI  - Image-guided core-needle breast biopsy is an accurate technique to evaluate
      patients with nonpalpable imaging abnormalities.
AB  - OBJECTIVE: The goal was to evaluate one institution's experience with image
      guided core-needle breast biopsy (IGCNBB) and compare the pathologic results with
      wire-localized excisional breast biopsy (WLEBB) for patients with positive cores
      and the mammographic surveillance results for patients with negative cores.
      SUMMARY BACKGROUND DATA: IGCNBB is becoming a popular, minimally invasive
      alternative to WLEBB in the evaluation of patients with nonpalpable
      abnormalities. METHODS: This study includes all patients with nonpalpable breast
      imaging abnormalities evaluated by IGCNBB from July 1993 to February 1997.
      Patients with positive cores (atypical hyperplasia, carcinoma in situ, or
      invasive carcinoma) were evaluated by WLEBB. Patients with negative cores (benign
      histology) were followed with a standard mammographic protocol. IGCNBB results
      were compared with WLEBB results to determine the sensitivity and specificity for
      each IGCNBB pathologic diagnosis. RESULTS: Of 1440 IGCNBBs performed during the
      study period, 1106 were classified as benign, and during surveillance follow-up
      only a single patient was demonstrated to have a carcinoma in the index part of
      the breast evaluated by IGCNBB (97.3% sensitivity, 99.7% specificity). IGCNBB
      demonstrated atypical hyperplasia in 72 patients, 5 of whom refused WLEBB. The
      remaining 67 patients were evaluated by WLEBB: nonmalignant findings were found
      in 31, carcinoma in situ was found in 25, and invasive carcinoma was found in 11
      (100% sensitivity, 88.8% specificity). IGCNBB demonstrated carcinoma in situ in
      84 patients; WLEBB confirmed carcinoma in situ in 54 and invasive carcinoma in 30
      (65.4% sensitivity, 97.7% specificity). IGCNBB demonstrated invasive carcinoma in
      178 patients. Three were lost to follow-up. On WLEBB, 173 of the remaining 175
      had invasive carcinoma; the other 2 patients had carcinoma in situ (80.8%
      sensitivity, 99.8% specificity). CONCLUSIONS: An IGCNBB that demonstrates
      atypical hyperplasia or carcinoma in situ requires WLEBB to define the extent of
      breast pathology. Mammographic surveillance for a patient with a benign IGCNBB is
      supported by nearly 100% specificity. An IGCNBB diagnosis of invasive carcinoma
      is also associated with nearly 100% specificity; therefore, these patients can
      have definitive surgical therapy, including axillary dissection or mastectomy,
      without waiting for the pathologic results of a WLEBB. Based on the authors'
      findings, IGCNBB can safely replace WLEBB in evaluating patients with nonpalpable
      breast abnormalities.

PMID- 9637556
TI  - Effects of 5-azacytidine and butyrate on differentiation and apoptosis of hepatic
      cancer cell lines.
AB  - OBJECTIVE: To determine the cellular effects of 5-azacytidine (5-azaC) and sodium
      butyrate on two human liver cancers, HepG2 and Hep3B. SUMMARY BACKGROUND DATA:
      Primary liver cancer is a significant health problem; treatment options are
      limited and prognosis is poor. Recent studies have focused on the role that
      programmed cell death (i.e., apoptosis) plays in both normal and neoplastic
      growth: certain genes can either suppress (e.g., Bcl-2, Bcl-xL) or promote (e.g.,
      Bik, Bax, Bak) apoptosis. The identification of novel agents targeted to specific
      molecular pathways may be beneficial in the treatment of this disease. METHODS:
      Human liver cancer cell lines HepG2 and Hep3B were treated with 5-azaC alone,
      butyrate alone, or 5-azaC and butyrate. Morphologic and proliferative changes
      were assessed by light microscopy and 5-bromo-2'-deoxyuridine staining; flow
      cytometry was used to determine cell cycle characteristics. Apoptosis was
      assessed by DNA laddering and the in situ apoptosis detection assay using the TdT
      mediated dUTP nick end labeling method. In addition, total RNA and protein were
      analyzed by ribonuclease protection and Western blot, respectively, to assess
      changes in the expression of apoptosis-related genes. RESULTS: Treatment with
      either 5-azaC or butyrate inhibited cell growth and induced apoptosis in both
      HepG2 and Hep3B cells; the combination of 5-azaC and butyrate was not more
      effective than either agent alone. 5-azaC alone resulted in a more differentiated
      appearing morphology and G2 cell cycle arrest in both cell lines. Treatment with
      5-azaC or butyrate affected the expression levels of proteins of the Bcl-2
      family. CONCLUSIONS: Both 5-azaC and butyrate induced apoptosis in the HepG2 and
      Hep3B liver cancer cells; 5-azaC treatment alone produced G2 arrest in both cell
      lines. Proteins of the Bcl-2 family may play a role in the cellular changes that
      occur with treatment, but further studies are required to define this potential
      role. Products of the apoptotic pathway may prove to be useful therapeutic
      targets in the treatment of hepatic cancers.

PMID- 9637558
TI  - Orthodontic Centers of America letter brings comments.

PMID- 9637559
TI  - Long-term concerns.

PMID- 9637560
TI  - Early treatment is a very strong tendency between the orthodontists and
      dentofacial orthopedists.

PMID- 9637561
TI  - A longitudinal laser fluorescence study of white spot lesions in orthodontic
      patients.
AB  - Orthodontic treatment with fixed appliances increases the caries risk in young
      persons. The aim of this study was to apply a new caries diagnostic method,
      quantitative laser fluorescence, for longitudinal in vivo quantification of
      changes in incipient enamel lesions related to fixed orthodontic appliances.
      Seven young patients with active caries lesions disclosed at removal of the
      orthodontic brackets and bands were enrolled in the study. Caries preventive
      measures were intensified, including dietary advice, oral hygiene instructions,
      and the regular use of a fluoride dentifrice. The caries lesions were monitored
      with the quantitative laser fluorescence method after removal of the brackets and
      once a month thereafter. For each lesion, three quantities were measured: lesion
      area (mm2), mean fluorescence loss (%) over the lesion, and maximum loss of
      fluorescence (%) in the lesion. During a 1-year follow-up period, the areas of
      the lesions decreased and the enamel fluorescence lost was partly regained
      indicating that a remineralization process had occurred. It was concluded that
      quantitative laser fluorescence seems suitable for in vivo monitoring of mineral
      changes in incipient enamel lesions, and useful for the evaluation of preventive
      measures in caries prone persons, such as orthodontic patients.

PMID- 9637562
TI  - Nasal obstruction and facial growth: the strength of evidence for clinical
      assumptions.
AB  - The orthodontic relevance of nasorespiratory obstruction and its effect on facial
      growth continues to be debated after almost a century of controversy. The
      continuing interest in nasal obstruction is fueled by strong convictions, weak
      evidence, and the prevailing uncertainty of cause and effect relationships that
      exist. The essence of any debate is to provide opposing evidence from which a
      majority vote is obtained. Political issues may be appropriately resolved by such
      means as a majority vote. Scientific issues, however, can only be resolved by
      data and appropriately structured hypotheses put to the test. One of the problems
      in debating nasorespiratory obstruction and facial growth is the inability to
      provide unequivocal answers to such issues as: How much nasal obstruction is
      clinically significant? At what age is the onset critical and for how long does
      it have to exist before an effect on facial growth can be expected? To provide
      unequivocal answers, clinical studies need to be designed to identify and
      quantify the degree of nasorespiratory obstruction and compare individuals for
      any clinically relevant differences. The purpose of this article is to review the
      available evidence. If both data and untested popular beliefs are subjected to
      the same rigorous criteria, indications for the orthodontic management of
      patients with nasorespiratory obstruction may gain a more rational approach to
      treatment recommendations.

PMID- 9637563
TI  - Maxillary protraction: treatment and posttreatment effects.
AB  - This study evaluated the treatment response and posttreatment follow-up of
      children with Class III malocclusions treated with palatal expansion and reverse
      pull face mask to the maxilla. The sample included 22 white children, 9 boys and
      13 girls. Treatment began at a mean age of 9.8 years (range 5.6 to 13.3 years)
      and lasted 0.7 years (range 0.3 to 1.3 years). With a protraction force of 600 to
      800 gm, the patients were treated until a 2 mm positive overjet had been
      attained. Radiographs were taken before treatment (T1), immediately after face
      mask treatment (T2), and 1.4 years after treatment (T3). An age and sex matched
      sample of untreated white schoolchildren served as normal controls. The results
      showed that the anterior maxilla was protracted forward 1.6 mm per year more than
      normal. The posterior maxilla dropped inferiorly more than the anterior maxilla.
      The mandible was rotated downward and backward, while the lower incisors were
      uprighted. The effects on the mandible were attributed to a significant chincup
      effect exerted by the face mask. After treatment, the maxilla relapsed relatively
      backward in the anterior and upward in the posterior, negating some of the
      treatment results. The mandible resumed a normal growth direction, and the lower
      incisors flared more than normal.

PMID- 9637564
TI  - In vitro study of 24-hour and 30-day shear bond strengths of three resin-glass
      ionomer cements used to bond orthodontic brackets.
AB  - Interest in using composite resin-glass ionomer hybrid cements as orthodontic
      bracket adhesives has grown because of their potential for fluoride release. The
      purpose of this pilot study was to compare shear bond strengths of three resin
      glass ionomer cements (Advance, Fuji Duet, Fuji Ortho LC) used as bracket
      adhesives with a composite resin 24 hours and 30 days after bonding. The amount
      of adhesive remaining on the debonded enamel surface was scored for each
      adhesive. Mesh-backed stainless-steel brackets were bonded to 100 extracted human
      premolars, which were stored in artificial saliva at 37 degrees C until being
      tested to failure in a testing machine. The hybrid cements, with one exception,
      had bond strengths similar to those of the composite resin at 24 hours and 30
      days. Fuji Ortho LC had significantly lower bond strengths (ANOVA p < or = 0.05)
      than the other adhesives at 24 hours and 30 days when it was bonded to unetched,
      water-moistened enamel. Adhesive-remnant scores were similar for all cements,
      except for cement Fuji Ortho LC when it was bonded to unetched enamel. The resin
      glass ionomer cements we tested appear to have bond strengths suitable for
      routine use as orthodontic bracket-bonding adhesives.

PMID- 9637565
TI  - Unexpected temporomandibular joint findings during fixed appliance therapy.
AB  - Six hundred consecutively debonded patients were retrospectively examined for the
      development of any temporomandibular joint signs or symptoms that developed
      during orthopedic/orthodontic treatment. Sixteen (2.6%) patients were found to
      have developed unexpected temporomandibular joint findings during treatment.
      Considering such a small sample, no conclusive results could be found, but
      several tendencies seemed to be apparent. Those types of patients who seemed to
      be most predisposed to developing temporomandibular joint problems included
      female Class II patients with excessive overjet and overbite and moderate to
      severe crowding of the lower arch. Ninety-three percent of the patients
      experienced posterior net condylar change in spite of using several different
      treatment mechanics. The types of treatments used included FJO appliances,
      headgear, Class II and Class III elastics, no elastics of any kind, extraction
      and nonextraction. This small study seems to suggest that temporomandibular joint
      signs and symptoms are changing, inconsistent, and ephemeral in many orthodontic
      patients regardless of the treatment mechanics.

PMID- 9637566
TI  - A formula for the displacement of an arch wire when subjected to a second-order
      couple.
AB  - A new formula, expressing the local angular displacement of an orthodontic beam
      when subjected to a second-order couple applied at midspan, has been developed
      and analyzed. The computed displacements were compared with the results of ex
      vivo testing. There was good agreement between the results from the theoretical
      evaluation and the bench testing. Second-order activation of an orthodontic beam
      can be described in four sequential phases. The initial displacement is
      influenced by the second-order clearance between bracket-slot and wire as well as
      the relationship between the bracket-slot width and interbracket distance. During
      phase II there is a nonlinear relationship between applied couple and rotational
      displacement. Within phases three and four displacement is linearly related to
      the interbracket distance, provided the relationship between the bracket-slot
      width and interbracket distance remains constant. For a given tooth size, the
      second-order beam stiffness is exponentially related to bracket width. The
      experiments also show that even small deflections of thin stainless steel wires
      can lead to second-order couples of large magnitudes when using a clinically
      relevant interbracket distance. Consequently, it is important that the
      orthodontist evaluates his or her choice of bracket width and arch wire stiffness
      in each clinical case in order to avoid supra-physiologic force levels.

PMID- 9637567
TI  - Functional treatment of condylar fractures in adult patients.
AB  - Functional treatment of condylar fractures in adult patients usually follows the
      closed reduction/maxillomandibular fixation approach. Some of the problems
      arising when functional appliances (i.e., activator) are used have been
      identified and presented here, especially in patients where fractured parts are
      dispositioned/dislocated. The cause is discussed and a different functional
      approach is proposed that yields good results.

PMID- 9637568
TI  - Compliance with infection-control procedures among Illinois orthodontists.
AB  - The authors of previous studies have reported an increasing percentage of
      orthodontists complying with infection-control procedures in their offices, yet
      compliance was found to be less than ideal. In this study we surveyed Illinois
      orthodontists to evaluate their compliance with the infection-control guidelines
      established by the American Dental Association and the Centers for Disease
      Control and Prevention. This study is an addition to a small number of studies in
      the field of orthodontics on infection-control procedures. The study population
      was taken from the World Directory of Orthodontists, which contains 374 listings
      for the state of Illinois. Responses were received from 140 orthodontists, for a
      response rate of 37%. Thirty-two percent of the responding orthodontists stated
      that they always wear masks; 13% said they never do. Almost 97% of the
      orthodontists said they always wear gloves, and no orthodontist reported never
      wearing gloves. Nearly 64% of the orthodontists reported always using eyewear,
      and 34% said they wear gowns, whereas only 5% do not wear eye protection and 35%
      never wear gowns. With regard to instruments and pliers, most of the
      orthodontists reported using dry-heat ovens (72% and 80%, respectively), whereas
      nearly 58% said they use chemical disinfection to some extent on instruments and
      39% said they use chemical disinfection on pliers. Only 51% of the orthodontists
      surveyed in our study reported using a steam autoclave to sterilize handpieces,
      whereas 27% said they use dry-heat ovens, 11% reported using chemical vapor, and
      37% said they use chemical disinfection. In conclusion, compliance with infection
      control procedures among orthodontists has improved from recent studies but is
      still less than full compliance.

PMID- 9637569
TI  - Nickel hypersensitivity reaction before, during, and after orthodontic therapy.
AB  - Nickel is a strong biological sensitizer and consequently may induce a delayed
      hypersensitivity reaction (type IV immune response). Because nickel is a
      component of the majority of the orthodontic alloys, the objectives of this cross
      sectional study were to determine the prevalence of nickel hypersensitivity
      reaction before, during, and after orthodontic therapy with conventional
      stainless steel brackets and wires; to evidence the induction of this reaction by
      the orthodontic appliances; and to characterize the nickel hypersensitive
      persons. Nickel patch tests and a questionnaire were used to evaluate the
      hypersensitivity to this metal. The total sample consisted of 170 patients, 105
      females and 65 males, from the orthodontic department at Bauru Dental School,
      University of Sao Paulo. They were divided into three groups as follows: A (n =
      60), patients before the beginning of orthodontic therapy; B (n = 66), patients
      currently undergoing orthodontic treatment, and C (n = 44), patients who had
      undergone orthodontic treatment previously. The chi-square test (chi2) showed an
      allergic reaction in 28.3% of the total sample with 23% female and 5.3% male.
      This indicated a gender difference (chi2 = 10.75, p < 0.001). There was a
      positive association between nickel hypersensitivity and previous personal
      allergic history to metals (chi2 = 34.88, p < 0.0001) as well as with the daily
      use of metal objects (chi2 = 11.95, p < 0.0005). There was no statistically
      significant difference in the prevalence of contact dermatitis among the three
      groups (chi2 = 0.39, p = 0.848). This suggests that orthodontic therapy with
      conventional stainless steel appliances does not initiate or aggravate a nickel
      hypersensitivity reaction.

PMID- 9637570
TI  - Mandibular changes in persons with untreated and treated Class II division 1
      malocclusion.
AB  - The growth potential of individuals with Class II malocclusions is of interest to
      the practicing orthodontist because such malocclusions constitute a significant
      percentage of cases. The purpose of this study was to evaluate on cross-sectional
      and longitudinal bases the changes in mandibular length and relationship and
      maxillary-mandibular relationships in untreated Class II subjects from deciduous
      to permanent dentition and also to evaluate the effects of orthodontic treatment,
      with and without the extraction of first premolars, on these relationships. Class
      II samples were compared with matched normal, untreated individuals. The Class II
      division 1 (Class II/1) untreated sample comprised 30 subjects, 15 males and 15
      females. Each subject had a complete set of data at three stages of dental
      development-namely, Stage I, after the completion of eruption of the deciduous
      dentition; Stage II, at the time when the permanent first molars and most of the
      incisors have erupted (i.e., in mixed dentition); and Stage III, at the
      completion of eruption of the permanent dentition, excluding third molars. The
      Class II treated sample comprised 44 subjects (21 males, 23 females) treated with
      four first-premolar extractions and 47 subjects (20 males, 27 females) treated
      without extraction. Treatment was accomplished with the use of an edgewise
      appliance, appropriate extraoral traction, and Class II elastics. The extraction
      decision was based mainly on the presence of crowding and profile consideration.
      Records on 35 normal subjects (20 males, 15 females) were available from the Iowa
      Longitudinal Facial Growth Study. Cephalograms for the normal individuals were
      matched to the corresponding ages of the Class II cases. With regard to these
      findings, few consistent differences were noted between the untreated Class II/1
      and normal subjects on cross-sectional comparisons. The differences in mandibular
      length and position were more evident in the early stages of development than at
      later stages. Longitudinal comparisons of growth profiles indicated that the
      growth trends were essentially similar between the untreated Class II/1 and
      normal subjects in the various parameters compared. The comparisons of growth
      magnitude indicated the presence of greater skeletal facial convexity in the
      untreated Class II/1 subjects, accompanied by a tendency for a more retruded
      mandible. Initial comparisons between the Class II/1 treated groups and normal
      subjects indicated that the Class II/1 malocclusions were associated with a
      larger overjet, deeper overbite, and greater ANB angle. After a 5-year treatment
      and observation period, an overall "normalization" in the mandibular and
      maxillary-mandibular skeletal relationships was noted in the treated Class II/1
      subjects in both the extraction and the nonextraction groups compared with normal
      subjects. The changes were more pronounced in the extraction group.

PMID- 9637571
TI  - Soft tissue adaptability to hard tissues in facial profiles.
AB  - The purpose of this study was to investigate soft tissue adaptability to hard
      tissue. A canonical correlation analysis was performed in an attempt to assess
      the relationships between hard tissue structure and soft tissue profile in the
      static state. For the dynamic study, multiple-regression analysis was performed
      to identify the changes of soft tissue profiles associated with the retraction of
      upper and lower incisors. The samples comprised lateral cephalograms from 297
      Japanese women for the static canonical correlation analysis and 32 sets of
      lateral cephalograms of pre- and posttreatment adult orthodontic patients for the
      dynamic multiple-regression analysis. In the static state, the vertical dimension
      of lower facial height and the position of the lower incisors were associated
      with the thickness of the upper-lip vermilion and soft tissue B, and the
      horizontal relationships between upper- and lower-jaw positions were associated
      with the thickness of upper lips and of pogonion (soft tissue chin). In the
      dynamic state, the results indicated that the changes of stomion and lower lip
      could be predicted and strongly reflected the changes of the hard tissue. On the
      contrary, the change of the upper lip showed a weaker association with the hard
      tissue changes. Predictions of chin form described by the soft tissue B and soft
      tissue pogonion were less accurate than estimates of upper- and lower-lip form.
      Chin form was influenced by the hard tissue structures such as ANB angle and
      lower-facial height rather than by changes in lower- and upper-incisor
      retraction.

PMID- 9637572
TI  - Six blind men and the elephant: a paradox story on relapse.

PMID- 9637573
TI  - Litigation, legislation, and ethics. Defining the standard of care.

PMID- 9637574
TI  - Role of the thymus in pediatric HIV-1 infection.
AB  - Several lines of evidence suggest that HIV-1 is present in the thymus during HIV
      1 infection. Precursors to mature CD4+ T lymphocytes develop in the thymus, which
      suggests that thymic infection may play a role in the CD4+ T-cell decline
      observed during the course of pediatric HIV-1 infection. We illustrate, through
      mathematical modeling, the potential effects of thymic infection on the course of
      pediatric AIDS disease progression. We find that infection in the thymus not only
      can supplement peripheral infection but can help explain the faster progression
      in pediatric cases, as well as the early and high viral burden.

PMID- 9637575
TI  - Chemokine receptor CCR2b 64I polymorphism and its relation to CD4 T-cell counts
      and disease progression in a Danish cohort of HIV-infected individuals.
      Copenhagen AIDS cohort.
AB  - We have investigated the role of the recently described mutation in CCR2b named
      64I in relation to HIV resistance, CD4 T-cell counts, and disease progression in
      Danish individuals by polymerase chain reaction (PCR)-based methods as well as
      sequenced full-length CXCR4 and CCR5 genes from HIV-infected long-term
      nonprogressors for possible mutations. In total, 215 Danish individuals were
      analyzed for 64I allele frequency; disease progression was followed in 105 HIV-1
      positive homosexual Danish men from their first known positive HIV-1 test result
      and up to 11 years. In 87 individuals, the CD4 T-cell count was monitored
      closely. We found no significant difference in 64I allele frequency between HIV-1
      seropositive persons (0.08), high-risk HIV-1-seronegative persons (0.11), and
      blood donors (0.06). No significant difference was observed in annual CD4 T-cell
      decline, CD4 T-cell counts at the time of AIDS, in AIDS-free survival as well as
      survival with AIDS, between 64I allele carriers and wild-type individuals. Among
      9 long-term nonprogressors, 2 carried the 64I allele, while none of 9 fast
      progressors carried the 64I allele. However, this was not significantly different
      (p=.47). Long-term nonprogression could not be explained by CXCR4 polymorphism or
      other polymorphisms in the CCR5 gene than the CCR5delta32 allele. Furthermore, we
      were not able to detect any significant independent effect of the 64I allele on
      development to AIDS, overall survival, and annual CD4 T-cell decline in this
      cohort.

PMID- 9637576
TI  - Adherence to antiretroviral and pneumocystis prophylaxis in HIV disease.
AB  - BACKGROUND: Medication nonadherence in the treatment of chronic diseases
      compromises the effectiveness of therapy. Little information is available about
      the extent of medication adherence or determinants of medication adherence in HIV
      disease, an issue of increasing importance in this new therapeutic era of
      combination antiretroviral therapy. METHODS: We studied 244 HIV-infected Medicaid
      insured patients attending an HIV hospital-based clinic regarding the extent of
      and predictors of adherence to antiretroviral therapy and Pneumocystis carinii
      pneumonia (PCP) prophylaxis. Patients were asked to report medications being
      taken, patterns of use, and knowledge and attitudes about HIV therapies. Medical
      record report of type, dose, and frequency of medication was compared with self
      report using the kappa statistic. Urine sulfamethoxazole assay was obtained from
      patients prescribed sulfamethoxazole-trimethoprim. RESULTS: Among patients
      prescribed antiretroviral therapy, 60% reported > or = 80% adherence in the
      previous 7 days; 49% reported > or = 80% adherence with PCP prophylaxis in the
      previous seven days. Seventy-nine percent of patients who reported taking daily
      sulfamethoxazole-trimethoprim had detectable urinary sulfamethoxazole. In
      multivariate analysis, > or = 80% adherence to antiretroviral therapy was
      associated with taking medication < or = twice a day (odds ratio [OR]=1.44; 95%
      confidence interval [CI], 1.01, 1.96), being likely to take medication when not
      at home, (OR=1.41; 95% CI, 1.04, 2.00) and patients' belief in their ability to
      adhere to therapy (OR=1.57; 95% CI, 1.13, 2.17). For PCP prophylaxis, > or = 80%
      adherence was associated with presence of family (OR=2.39; 95% CI, 1.01, 5.63)
      and patients' belief in their ability to adhere to therapy (OR=2.87; 95% CI, 1.44
      1.78). Sociodemographic characteristics and belief in the efficacy of medications
      were not associated with adherence. CONCLUSIONS: A relatively low level of
      adherence to antiretroviral therapy and PCP prophylactic regimens was found.
      Although our results are principally from patients receiving antiretroviral
      monotherapy, these findings may have important implications for patients
      receiving highly active antiretroviral therapy (HAART). Decreasing the complexity
      of antiretroviral regimens, and working with patients to modify identified
      barriers to adherence may improve effectiveness of medications and prolong
      survival.

PMID- 9637577
TI  - Maternal cell-free viremia in the natural history of perinatal HIV-1
      transmission: a meta-analysis.
AB  - We performed a meta-analysis of the predictive value of maternal cell-free viral
      load in vertical HIV-1 transmission, including 9 cohorts with 1115 mother-infant
      pairs (696 untreated and 419 treated women). The pooled rate of transmission in
      untreated women was 21.3% (95% confidence interval [CI], 18.3%-24.5%). The rates
      of transmission for untreated women in the <1000 copies/ml, 1000 to 9999
      copies/ml, and > or = 10,000 copies/ml categories were 5% (95% CI, 2%-11%), 15%
      (95% CI, 11%-20%) and 37% (95% CI, 29%-46% by random effects), respectively. The
      area under the receiver operating characteristic (ROC) curve in individual
      studies ranged from 0.67 to 1.00. The predictive performance of RNA differed
      between cohorts in which different percentages of transmitters had RNA values
      >10,000 copies/ml. When 95% of transmitters have RNA values >1000 copies/ml, 77%
      of nontransmitters would also have values above this cutoff. Transmission rates
      for treated women in the 1000 to 9999 copies/ml category (7%; 95% CI, 4%-11%,)
      and > or = 10,000 copies/ml category (18%; 95% CI, 12%-27%) were probably lower
      than those for untreated women, whereas the transmission rate for treated women
      with <1000 copies/ml was 5% (95% CI, 2%-11 %). Thus, the risk gradient between
      RNA categories seems attenuated in treated women. Several aspects of the design,
      analysis, and reporting of research in this area may be improved in the future
      with attention to selection and observer biases, multivariate adjustment, and
      technical consistency. Maternal HIV-1 RNA is a modest predictor of transmission
      for individual mothers, but a strong predictor of the average risk in groups of
      untreated mothers. Its discriminatory power is better in untreated than in
      treated populations and is better in cohorts with a high prevalence of elevated
      viral load values than in cohorts with generally low levels of viremia.

PMID- 9637578
TI  - Pilot randomized trial of education to improve self-management skills of men with
      symptomatic HIV/AIDS.
AB  - OBJECTIVE: To evaluate the acceptability, practicality, and short-term efficacy
      of a health education program to improve disease self-management in patients with
      symptomatic HIV/AIDS. DESIGN: Randomized controlled trial, baseline and 3-month
      follow-up questionnaire assessments. SETTING: San Francisco Bay communities.
      PARTICIPANTS: Seventy-one men with symptomatic HIV or AIDS were randomly assigned
      to a seven-session group educational intervention (N=34) or a usual-care control
      group (N=37). INTERVENTION: Interactive health education groups were used to
      teach wide-ranging disease self-management skills and information: symptom
      assessment and management, medication use, physical exercise, relaxation, doctor
      patient communication, and nutrition. Each group was led by two trained peer
      leaders (one of whom was HIV-positive) recruited from the community. MAIN OUTCOME
      MEASURES: The primary outcome of interest was symptom status. Secondary outcomes
      were self-efficacy and health behaviors. Analysis of covariance was used to
      compare experimental and control group mean outcomes, adjusting for baseline
      value differences. RESULTS: The symptom severity index (number of symptoms
      moderate or greater severity) decreased in the experimental, and increased in the
      control group (-0.9 versus +0.5; p < .03). Pain, fatigue, and psychological
      symptoms were not significantly different between groups. Self-efficacy for
      controlling symptoms improved in the experimental, and decreased in the control
      group (+4 versus -7; p < .02). Changes in stress/relaxation exercises and
      HIV/AIDS knowledge were not different between groups. A trend was shown toward
      more frequent physical exercise in the experimental group compared with less in
      the control group (+1.3 versus -0.5 times/week; p=.06). CONCLUSIONS: Health
      education emphasizing self-management skills for HIV/AIDS patients can be
      implemented and evaluated and was accepted by patients, peer-leaders, and health
      care providers. Whether this educational program can lead to prolonged
      improvement in HIV symptoms and behaviors can be adequately addressed only by a
      larger trial of longer duration.

PMID- 9637579
TI  - Cardiac manifestations of HIV/AIDS: a review of disease spectrum and clinical
      management.
AB  - HIV and AIDS involve multiple organ systems. Lungs, brain, skin, gastrointestinal
      tract, kidneys, and heart are the major organs targeted by the direct effects of
      HIV infection and the secondary opportunistic complications of AIDS. Although
      most other organ system involvement has been extensively described in numerous
      studies and reviews, cardiac abnormalities related to HIV infection have remained
      less well characterized, partially because their pathogenesis was less clear and
      their clinical significance was uncertain. Most studies that have described
      cardiac complications in AIDS patients were postmortem, although some clinical
      series have been reported. It is now clear that cardiac involvement in AIDS
      patients is relatively common. Although most such conditions are clinically
      quiescent, some may have devastating and fatal outcomes. Pericardial effusion and
      myocarditis are among the most commonly reported abnormalities. Cardiomyopathy,
      endocarditis, and coronary vasculopathy have also been reported. In this review,
      we discuss the most common cardiac abnormalities in HIV-infected patients, as
      well as their clinical significance, clinical presentation, and management.

PMID- 9637580
TI  - Longitudinal HIV-1 RNA levels in a cohort of homosexual men.
AB  - HIV-1 RNA levels measured during early chronic infection strongly predict
      subsequent clinical events. In the short term, HIV-1 is in a steady state, but
      the stability of viral levels over time is incompletely understood. We used
      reverse transcriptase polymerase chain reaction (RT-PCR) to examine changes in
      serum HIV-1 RNA levels in 111 HIV-1-infected homosexual men during the period
      from 1982 to 1992 and their relation to clinical outcomes. HIV-1 RNA levels
      increased by a median of 0.08 log10 copies/ml/year (p=.0001). HIV-1 RNA levels
      rose either gradually or abruptly for the majority of subjects; 41% had no
      increase. Among subjects surviving at least 8 years, HIV-1 RNA was stable during
      the first 4 years after seroconversion (median. 0.00 log10 copies/ml/year), but
      rose in years five through eight (median, 0.06 log10 copies/ml/year; p=.04). The
      annual HIV-I RNA level was more predictive of AIDS (relative hazard [RH], 1.75
      per 0.5 log difference; 95% confidence interval [CI], 1.38-2.21; likelihood ratio
      [LR], 26.2) than the initial level alone (RH, 1.39; 95% CI. 1.10-1.76; LR, 8.5).
      We conclude that most HIV-1-infected persons lack a long-term viral setpoint and
      that failure to account for evolution of the viral level can lead to
      underestimation of the risk of progression.

PMID- 9637581
TI  - Accelerated changes (inflection points) in levels of serum immune activation
      markers and CD4+ and CD8+ T cells prior to AIDS onset.
AB  - The trajectories of change in CD4+ and CD8+ lymphocytes and serum neopterin and
      beta2-microglobulin (beta2M) levels were determined in 158 HIV-seropositive
      individuals during 5.5 years before a clinical AIDS diagnosis. Each patient was
      evaluated separately using a two-piece regression model with seven possible
      change points to identify any adverse change (inflection point) in the slopes of
      each immunologic marker of HIV infection. Two categories of subjects were
      distinguished for each marker--those with statistically significant inflection
      points and those who demonstrated a steady progression of changes to AIDS. Fifty
      nine percent had an inflection point for CD4+ T cells. The frequency of
      inflection points for CD8+ was 49%, for serum neopterin -48% and for beta2M -38%.
      Inflection points were found over a 4-year span. Three distinctive categories of
      inflection points were observed on the basis of their independent occurrence: one
      was in CD4+ T cells, another in CD8+ T cells, and a third in the serum markers of
      immune activation. The inflection point for CD4+ usually occurred prior to those
      for CD8+ T cells (p=.0002). The HIV-positive persons with inflection points were
      diagnosed with AIDS when immunologic parameters were significantly more abnormal
      than in those with steady progression (p < .0003). Thus, these two groups
      differed in the course of immune changes and in the levels of immune
      abnormalities associated with the occurrence of clinical AIDS.

PMID- 9637582
TI  - Motivation, recruitment, and screening of volunteers for a phase I/II HIV
      preventive vaccine trial in Thailand.
AB  - Data from recruitment and screening for a phase I/II preventive HIV-1 vaccine
      trial in Thailand were evaluated with respect to correlates of participation at
      each phase. Correlates included demographic variables, motivation for interest in
      the trial, and factors related to communication and contact. Participants were
      recruited at two sites through varied methods. The majority of prescreenees
      reported altruistic motives for interest in the trial and blood donors emerged as
      a group that may have been particularly altruistic. Findings indicated site
      differences in attrition during recruitment and screening, but not in enrollment
      into the vaccine trial. Blood donation and willingness to be contacted by phone
      at home were significantly related to making and keeping screening appointments.

PMID- 9637583
TI  - Expansion of clonotypic T-cell populations in the peripheral blood of
      asymptomatic Gran Chaco Amerindians infected with HTLV-IIB.
AB  - Peripheral blood mononuclear cells from asymptomatic HTLV-II-infected and
      uninfected Gran Chaco Amerindians were analyzed using polymerase chain reaction
      (PCR) for expansions of T-cell receptor (TCR) V-beta gene clonotypes. Analyses
      were performed using primer pairs designed to identify expanded T-cell familial
      clonotypes based on their unique TCR beta gene rearrangements. Of the 30 HTLV-IIB
      positive samples tested, five showed evidence of V-beta clonotypic T-cell
      expansion. Of the five expansions, two were monoclonotypic and the remaining
      three were oligoclonotypic. In comparison, 30 HTLV-II-negative Amerindians showed
      no evidence of clonotypic T-cell expansion. Amplified DNA from one of the
      monoclonotypic samples was subsequently cloned and sequenced and was found to
      have uniform variable/ diversity/joining sequences confirming its unique
      monoclonal T-cell expansion. This method of detecting clonal TCR beta gene
      rearrangements has the advantage over traditional Southern blot techniques of
      being more sensitive and specific even with suboptimal specimens. The prognostic
      significance of clonotypic T-cell expansion in a group such as the HTLV-II
      infected Gran Chaco Amerindians remains to be determined.

PMID- 9637584
TI  - Associations among HTLV-I, HTLV-II, and HIV in injecting drug users in Salvador,
      Brazil.

PMID- 9637585
TI  - HTLV-I/II seropositivity in populations at high risk for HIV-1 infection in
      Cordoba City, Argentina.

PMID- 9637586
TI  - Immunomodulatory effects of concurrent HTLV-I infection in strongyloidiasis.

PMID- 9637587
TI  - First report of HIV-2 infection in Argentina.

PMID- 9637588
TI  - The EEG findings in extratemporal seizures.
AB  - Extratemporal seizures originate from the frontal, central, parietal, occipital,
      and midline regions of the brain. The scalp EEG can show various types of
      interictal and ictal discharges consisting of spikes, spike and wave sharp waves,
      paroxysmal fast activity, or rhythmic activity in the beta, alpha, theta, or
      delta frequency ranges. The discharges can occur as focal, regional, lateralized,
      or secondarily generalized discharges. Discharges arising from the frontal region
      are varied and at times complex. Centro-temporal spikes associated with benign
      epilepsy of childhood have a characteristic blunt spike and wave appearance.
      Centro-parietal spikes can occur in children with benign childhood epilepsy or in
      association with symptomatic epilepsies at any age. Occipital spike discharges
      have been seen in young children with visual problems, benign occipital epilepsy
      of childhood, the Sturge-Weber syndrome, and other symptomatic or structural
      lesions involving the occipital lobe. There may be problems with detection of the
      source of origin of seizures secondary to the anatomy of the various regions,
      deep foci, small restricted foci, rapid spread of epileptiform discharges, and
      contaminating effects of muscle and movement artifact. Depth or intracranial
      recordings may help in further localization of foci.

PMID- 9637589
TI  - The benign occipital epilepsies of childhood: an overview of the idiopathic
      syndromes and of the relationship to migraine.
AB  - Benign occipital epilepsy of childhood is an idiopathic partial epilepsy syndrome
      with elementary visual symptomatology, frequently associated with other ictal
      phenomena. Seizures are usually followed by postictal headache and are often
      associated with interictal occipital rhythmic paroxysmal EEG activity that
      appears only after eye closure. In some children the ictal visual symptoms or the
      interictal EEG abnormalities may not be demonstrated. The clinical and/or EEG
      manifestations of other forms of idiopathic partial or generalized epilepsy may
      be found in association. Occipital spikes in non-epileptic children with
      defective vision, occipital slow spike-and-wave found in some patients with the
      Lennox-Gastaut syndrome, focal epilepsy due to occipital lesions, seizures
      originating in the temporal lobe secondary to an occipital abnormality, and
      complicated or basilar migraine must be considered in the differential diagnosis.
      Early-onset benign occipital epilepsy or seizure susceptibility syndrome deserves
      to be considered separately. It has been defined by Panayiotopoulos as consisting
      of brief, infrequent attacks or prolonged status epilepticus and characterized by
      ictal deviation of the eyes and/or head and vomiting, occurring in children
      usually between the ages of 3 and 7 years. Advances in molecular genetics will
      help decide whether these two disorders are indeed distinct. Benign occipital and
      benign rolandic epilepsy are commonly associated with migraine. The selective
      involvement of the occipital lobe in migraine has not been fully explained. The
      association between benign occipital epilepsy and migraine is likely related to
      this underlying mechanism as well. The "fixation off" phenomenon or blocking of
      occipital epileptic discharges by eye opening is not specific to benign occipital
      epilepsy of childhood and may be found in symptomatic epilepsies as well.
      Migraine and epilepsy are distinct disorders, both as far as their
      pathophysiologic mechanisms and clinical symptomatology are concerned. There is
      however an overlap in some patients and a causal relationship may exist in some,
      leading to clinically distinct migraine epilepsy syndromes. Here too,
      clarification of the molecular basis of migraine and of epilepsy will throw light
      on the nature of the relationship between the two conditions.

PMID- 9637590
TI  - Symptomatic occipital lobe epilepsy.
AB  - Symptomatic occipital lobe epilepsy is increasingly recognized among patients
      with partial-onset seizures. Although traditional clinical and
      electroencephalographic criteria had defined occipital lobe epilepsy in the past,
      new neuroimaging techniques and the recognition of specific syndromes associated
      with occipital lobe epilepsy have improved the diagnosis and management of these
      patients. These syndromes include, among others, lesional occipital lobe epilepsy
      (congenital vs. acquired), MELAS, and epilepsy with bilateral occipital
      calcifications. The diagnosis of symptomatic occipital lobe epilepsy is improving
      as functional and structural neuroimaging techniques enable the detection of
      subtle abnormalities in such patients. This has had a direct impact on the
      correct classification of patients with benign occipital lobe epilepsy, basilar
      migraine, and symptomatic occipital lobe epilepsy. The common clinical symptoms,
      EEG patterns, and neuroimaging findings of these patients are discussed.

PMID- 9637591
TI  - Benign epilepsy of childhood with centrotemporal spikes.
AB  - Benign epilepsy of childhood with centrotemporal spikes (BECT) is the most common
      partial epilepsy syndrome in the pediatric age group, with an onset between age 3
      and 13 years. The typical presentation is a partial seizure with parasthesias and
      tonic or clonic activity of the lower face associated with drooling and
      dysarthria. Seizures commonly occur at night and may become secondarily
      generalized. They are usually infrequent and may not require antiepileptic drugs
      but, if treated, they tend to be easily controlled. Children with BECT are
      neurologically and cognitively normal. The EEG shows characteristic high-voltage
      sharp waves in the centrotemporal regions, which are activated with drowsiness
      and sleep. In this typical form, BECT is easily recognized. However, atypical
      cases are common and the definition of BECT can become blurred. Although further
      investigations are not required in cases with typical clinical and EEG findings
      and normal neurologic examinations, neuroimaging studies may be required in
      atypical cases to rule out other pathology. The long-term medical and
      psychosocial prognosis of BECT is excellent, with essentially all children
      entering long-term remission by mid-adolescence.

PMID- 9637592
TI  - Surgical treatment for perirolandic lesional epilepsy.
AB  - Our purpose was to evaluate the safety and efficacy of surgical treatment for
      perirolandic lesional epilepsy. We analyzed the records of 14 consecutive
      patients who underwent a stereotactic lesionectomy for intractable partial
      epilepsy between 1985 and 1994. All patients had a neuroimaging-identified lesion
      in the perirolandic cortex. The mean duration of follow-up was 6 years (range 1
      11 years). Thirteen patients (93%) had a significant improvement in seizure
      tendency. Eleven patients (78%) were rendered seizure-free. Morbidity occurred in
      only one patient, who experienced an increased monoparesis after surgery.
      Stereotactic lesionectomy is an effective surgical strategy in patients with
      perirolandic lesional epilepsy. The recent development of functional brain
      imaging using subtraction ictal single-photon emission computed tomography co
      registered with volumetric magnetic resonance imaging has been shown to be a
      reliable indicator of epileptic brain tissue that may significantly alter the
      preoperative evaluation in patients with extratemporal seizures.

PMID- 9637593
TI  - Mesial frontal epilepsy.
AB  - The mesiofrontal cortex comprises a number of distinct anatomic and functional
      areas. Structural lesions and cortical dysgenesis are recognized causes of mesial
      frontal epilepsy, but a specific gene defect may also be important, as seen in
      some forms of familial frontal lobe epilepsy. The predominant seizure
      manifestations, which are not necessarily strictly correlated with a specific
      ictal onset zone, are absence, hypermotor, and postural tonic seizures. Other
      seizure types also occur. The task of localization of the epileptogenic zone can
      be challenging, whether EEG or imaging methods are used. Successful localization
      can lead to a rewarding outcome after epilepsy surgery, particularly in those
      with an imaged lesion.

PMID- 9637594
TI  - Lateral frontal lobe seizures.
AB  - On the basis of cytoarchitectural and functional studies, the frontal lobe can be
      subdivided into the primary motor cortex, premotor cortex, prefrontal cortex, and
      the limbic and paralimbic cortices. However, we are still a long way from clearly
      identifying individual frontal lobe epilepsies. Instead, we are limited to a
      discussion of frontal lobe seizures arising from various regions of the frontal
      lobe. Supplementary motor area epilepsy and perirolandic epilepsy have been quite
      well defined, in contrast to syndromes involving other regions of the frontal
      lobe. Recent technological advances in neuroimaging, electroencephalography,
      magnetoencephalography and detailed videotape analysis of seizure semiology may
      enable us to delineate these frontal lobe syndromes with better accuracy, thereby
      improving outcome after epilepsy surgery.

PMID- 9637595
TI  - Motor and sensory mapping of the frontal and occipital lobes.
AB  - In patients with intractable epilepsy, surgical resections are performed with the
      primary goal of improving seizure control. The risk is that the resections may
      also remove tissues crucial for normal activities. The goal of surgical planning
      is therefore to determine as accurately as possible the regions of seizure onset
      and the regions controlling important functions, so that one can determine what
      to remove and what to leave in place. Clinical functional localization has been
      performed using cortical stimulation for over half a century, using both
      intraoperative and extraoperative methods. Signal averaging also has been widely
      used. More recently, techniques based on analysis of EEG in the frequency domain
      have shown promise. The methods appear to accurately indicate the function of the
      region assessed but do not necessarily predict functional consequences of
      resection. We review these methods, their indications, and the results obtained
      by their use.

PMID- 9637596
TI  - Multiple subpial transection in patients with extratemporal epilepsy.
AB  - Multiple subpial transection (MST) was developed to permit the treatment of
      partial epilepsies that reside in or encroach on eloquent cortex (language and
      sensorimotor cortex). It was conceived after the discoveries of the columnar
      organization of neocortex and that expression and spread of seizures utilize the
      transverse fiber network. Although the technique is simple in principle, it takes
      a skilled and practiced hand to avoid damage to the neocortical columns and
      vascular supply. The efficacy in controlling seizures with MST in extratemporal
      epilepsy is similar to that of resective surgery. Activities of daily living are
      not adversely impacted by MST. MST is a viable alternative to resection in
      extratemporal epilepsy.

PMID- 9637597
TI  - Seizure patterns of Mongolian gerbils subjected to a prolonged weekly test
      schedule: evidence for a kindling-like phenomenon in the adult population.
AB  - PURPOSE: Mongolian gerbils (Meriones unguiculatus) seize in response to sensory
      stimulation and forced exploratory behavior, but the incidence and severity of
      their seizures are variable. We wished to characterize the seizure pattern of
      gerbils from our breeding colony. METHODS: Ninety-three gerbils aged 1-16 months
      were tested for a mean of 24 consecutive weeks and assigned to a category
      according to their seizure pattern. Frequency distribution histograms of the mean
      scores assigned every 5 weeks were plotted for each category. Mean age, number of
      seizures, onset of the first facial and forelimb myoclonus, and of the first
      generalized tonic-clonic seizure (GTCS) were compared among categories. We
      performed correlation analysis between onset of seizures and animal age. RESULTS:
      From the 93 tested, no seizure-resistant gerbils could be isolated. Four major
      categories were distinguished. Category 1, highly seizure-sensitive gerbils
      (39%), exhibited seizures from the first few weeks of test on. Category 2,
      consisting of approximately 37%, were seizure-free for the first three to six
      consecutive tests, later developing facial and forelimb myoclonus and eventually
      GTCS. Because such progressive development of seizures was similar to that
      occurring upon electrical kindling, the gerbils were classified as kindled-like
      (KL). Among KL gerbils, older individuals were significantly more refractory to
      seizures. In category 3, gerbils (10%) exhibited inconsistent seizure behavior.
      Category 4 consisted of significantly younger animals (11%) with rapid progress
      to generalized seizures. CONCLUSIONS: Seizures of progressive severity can be
      induced in adult gerbils with a prolonged test regimen. As a consequence, the
      number of regularly seizing gerbils in a colony can be increased. Prolonged tests
      starting at a defined age may help characterize seizure development better in
      this genetic model of limbic epilepsy.

PMID- 9637598
TI  - [31P]/[1H] nuclear magnetic resonance study of mitigating effects of GYKI 52466
      on kainate-induced metabolic impairment in perfused rat cerebrocortical slices.
AB  - PURPOSE: Kainic acid (KA) has long been used in experimental animals to induce
      status epilepticus (SE). A mechanistic implication of this is the association
      between excitotoxicity and brain damage during or after SE. We evaluated KA
      induced metabolic impairment and the potential mitigating effects of GYKI 52466
      [1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine] in
      superfused rat cerebral cortical slices. METHODS: Interleaved [31P]/[1H] magnetic
      resonance spectroscopy (MRS) was used to assess energy metabolism, intracellular
      pH (pHi), N-acetyl-L-aspartate (NAA) level, and lactate (Lac) formation before,
      during, and after a 56-min exposure to 4 mM KA in freshly oxygenated artificial
      cerebrospinal fluid (oxy-ACSF). RESULTS: In the absence of GYKI 52466 and during
      the KA exposure, NAA, PCr, and ATP levels were decreased to 91.1 +/- 0.8, 62.4 +/
      3.9, and 59.1 +/- 4.3% of the control, respectively; Lac was increased to 118.2
      +/- 2.1 %, and pH, was reduced from 7.27 +/- 0.02 to 7.13 +/- 0.02. During 4-h
      recovery with KA-free ACSF, pHi rapidly and Lac gradually recovered, NAA
      decreased further to 85.5 +/- 0.3%, and PCr and ATP showed little recovery.
      Removal of Mg2+ from ACSF during KA exposure caused a more profound Lac increase
      (to 147.1 +/- 4.0%) during KA exposure and a further NAA decrease (to 80.4 +/-
      0.5%) during reperfusion, but did not exacerbate PCr, ATP, and pHi changes.
      Inclusion of 100 microM GYKI 52466 during KA exposure significantly improved
      energy metabolism: the PCr and ATP levels were above 76.6 +/- 2.1 and 82.0 +/-
      2.9% of the control, respectively, during KA exposure and recovered to 101.4 +/-
      2.4 and 95.0 +/- 2.4%, respectively, during reperfusion. NAA level remained at
      99.8 +/- 0.6% during exposure and decreased only slightly at a later stage of
      reperfusion. CONCLUSIONS: Our finding supports the notion that KA-induced SE
      causes metabolic disturbance and neuronal injury mainly by overexcitation through
      non-N-methyl-D-aspartate (NMDA) receptor functions.

PMID- 9637599
TI  - Phenytoin blocks the reversal of a classically conditioned discriminative
      eyeblink response in rabbits.
AB  - PURPOSE: Cognitive deficits associated with chronic treatment with phenytoin
      (PHT) have been reported. PHT blocks transfer from a signaled appetitive bar
      press to an active avoidance response in rats. We investigated the effects of PHT
      and the prodrug fosphenytoin in rabbits required to learn a discrimination and
      reversal of a classical eyeblink conditioning paradigm. METHODS: Before drug
      treatment was started, rabbits were trained to produce a discriminated eyeblink
      response. PHT (n = 7) was administered centrally or the prodrug fosphenytoin (n =
      2) was given systemically. Control animals were similarly treated centrally with
      either saline (n = 3) or no drug treatment (n = 13). Rabbits were then challenged
      with a stimulus reversal while being maintained on the respective drug. RESULTS:
      On the first day of reversal training, control animals typically displayed high
      response rates to both tones, followed by a reduction in responsiveness to the
      new conditioned stimulus (CS-) in the ensuing days. In contrast, PHT-treated
      animals failed to suppress responsiveness to the new CS-. CONCLUSIONS: The
      response patterns observed are similar to those observed in rabbits with
      hippocampal ablations, leading us to suggest that the adverse effects of
      phenytoin may be due to actions in the hippocampus.

PMID- 9637600
TI  - Oral health and dental treatment needs in Nigerian patients with epilepsy.
AB  - PURPOSE: We determined the prevalence of oral disorders and the dental treatment
      needs of outpatients with epilepsy. METHODS: A questionnaire was administered to
      56 consecutive patients (35 males, 21 females) presenting to an outpatient
      clinic. All patients underwent dental examinations. The clinical and diagnostic
      features of each patient's epilepsy were also obtained. RESULTS: The mean age (+/
      SD) of the patients was 25.1 +/- 12.1 years (range, 12-56 years). Of 9 patients
      receiving phenytoin (PHT) monotherapy, 3 (33.3%) had gingival hypertrophy; 15 of
      18 (83.3%) patients receiving PHT in combination with phenobarbital (PB)
      manifested the disorder. Traumatized anterior teeth were found in 26 (46.4%)
      patients with the males significantly more affected than females (p = 0.02). When
      the dental treatment needs were considered, 24 (42.9%) patients required dental
      prophylaxis with oral hygiene instruction, and an equal number required various
      types of restorative treatments. Only 13 patients (23.2%) had previously visited
      a dental clinic; the 43 (76.8%) who had never sought dental treatment claimed
      they did not see any need for it. CONCLUSIONS: Our study showed an increased
      predilection to anterior dental injuries in patients with epilepsy as compared
      with the prevalence earlier reported for those without epilepsy in Nigeria (p =
      0.00). There is a clear need for effective interaction between medical and dental
      practitioners in the management of epilepsy.

PMID- 9637601
TI  - Symptoms of depression and anxiety in pediatric epilepsy patients.
AB  - PURPOSE: We assessed rates of symptoms of anxiety and depression among pediatric
      patients with epilepsy. METHODS: We administered the Revised Child Manifest
      Anxiety Scale (RCMAS), and Child Depression Inventory (CDI) to 44 epilepsy
      patients aged 7-18 years (mean age 12.4 years). Demographic, socioeconomic, and
      epilepsy-related information was examined in relation to depression and anxiety
      scores. RESULTS: No patients had been previously identified to have depression or
      anxiety. However, 26% had significantly increased depression scores and 16% met
      criteria for significant anxiety symptomatology. CONCLUSIONS: Symptoms of
      depression and anxiety are common among pediatric patients with epilepsy and
      appear to be overlooked by care providers.

PMID- 9637602
TI  - Surgical outcome in patients with epilepsy with occult vascular malformations
      treated with lesionectomy.
AB  - PURPOSE: This retrospective study reports the long-term surgical outcome of
      patients with medically refractory epilepsy and vascular malformations who were
      treated with lesionectomy. A detailed analysis of surgical failures had been
      performed in an attempt to define predictors of surgical success and failure.
      METHODS: Fifteen patients with medically intractable epilepsy and
      angiographically occult vascular malformations (AOVMs) were treated surgically
      with lesionectomy at Duke University Medical Center. Lesionectomy consisted of
      removal of the AOVM and surrounding hemosiderin-stained brain only, without the
      use of electrocorticography (ECoG) to guide resection. RESULTS: Eleven (73%)
      patients are seizure free after lesionectomy. Three showed no significant
      improvement, and one patient died, presumably after a seizure. Age of onset,
      duration of seizures, age at resection, and gender did not affect outcome. All
      patients with neocortical AOVMs in whom EEG findings correlated with the site of
      the lesion were seizure free after lesional resection. Treatment failures were
      associated with the presence of multiple intracranial lesions, poorly localized
      or diffuse EEG findings, discordant positron emission tomography (PET) imaging,
      or with a lesion in close proximity to the limbic system. CONCLUSIONS:
      Lesionectomy, with removal of surrounding hemosiderin-stained brain, can be
      considered the procedure of choice in carefully selected patients with epilepsy
      with occult vascular malformations.

PMID- 9637603
TI  - Ictal scalp EEG in unilateral mesial temporal lobe epilepsy.
AB  - PURPOSE: We wished to determine the predictive significance of unilateral
      hippocampal atrophy and interictal spikes on localization of ictal scalp EEG
      changes and assess whether ictal EEG provides information that might change
      treatment or influence prognosis in patients with such characteristics of
      epilepsy. METHODS: We analyzed EEG seizure patterns in 118 seizures in 24
      patients with unilateral mesial temporal lobe epilepsy (MTLE) defined by typical
      clinical seizure semiology, unilateral hippocampal atrophy on magnetic resonance
      imaging (MRI) and unitemporal spikes on interictal EEG. Two blinded
      electroencephalographers independently determined morphology, location, and time
      course of ictal EEG changes. RESULTS: Lateralization was possible in 88.4-92.0%
      of seizures and always corresponded to the side of the interictal spike focus and
      of hippocampal atrophy on MRI. Although only 30.4-33.9% of seizures were
      lateralized at onset, a later significant pattern emerged (12.6-13.3 s after EEG
      seizure onset) that allowed lateralization in 82.4-91.0% of seizures with
      nonlateralized onset. Interobserver reliability for lateralization was excellent,
      with a K-value of 0.85. In most patients, either all (79.2-83.3%) or >50% (8.3
      16.7%) of seizures were lateralized. In only a small proportion of patients (4.2
      8.3%) were <50% of seizures lateralized. In 1 patient, no seizure could be
      lateralized by 1 electroencephalographer. The results of ictal EEG recordings did
      not alter the surgical approach and did not correlate with surgical outcome.
      CONCLUSIONS: We conclude that unilateral hippocampal atrophy on MRI and
      unitemporal interictal spikes can predict localization of ictal scalp EEG changes
      with a high degree of reliability and that ictal EEG provides no additional
      localizing information in this particular patient group.

PMID- 9637604
TI  - Real-time automated detection and quantitative analysis of seizures and short
      term prediction of clinical onset.
AB  - PURPOSE: We describe an algorithm for rapid real-time detection, quantitation,
      localization of seizures, and prediction of their clinical onset. METHODS:
      Advanced digital signal processing techniques used in time-frequency
      localization, image processing, and identification of time-varying stochastic
      systems were used to develop the algorithm, which operates in generic or
      adaptable "modes." The "generic mode" was tested on (a) 125 partial seizures
      (each contained in a 10-min segment) involving the mesial temporal regions and
      recorded using depth electrodes from 16 subjects, and (b) 205 ten-minute segments
      of randomly selected interictal (nonseizure) data. The performance of the
      algorithm was compared with expert visual analysis, the current "gold standard."
      RESULTS: The generic algorithm achieved perfect sensitivity and specificity (no
      false-positive and no false-negative detections) over the entire data set.
      Seizure intensity, a novel measure that seems clinically relevant, ranged between
      35.7 and 6129. Detection was sufficiently rapid to allow prediction of clinical
      onset in 92% of seizures by a mean of 15.5 s. CONCLUSIONS: This algorithm, which
      was implemented with a personal computer, represents a definitive step toward
      rapid and accurate detection and prediction of seizures. It may also enable
      development of intelligent devices for automated seizure warning and treatment
      and stimulate new study of the dynamics of seizures and of the epileptic brain.

PMID- 9637605
TI  - Predictive value of interictal epileptiform discharges during non-REM sleep on
      scalp EEG recordings for the lateralization of epileptogenesis.
AB  - PURPOSE: EEG recording during sleep is widely used in the assessment of epilepsy,
      particularly in candidates for surgery, yet the diagnostic value of this
      procedure is not well established. We evaluated the predictive reliability of
      interictal epileptiform discharges (IEDs) for localization in presurgical
      patients with temporal lobe epilepsy (TLE) during non-REM sleep. METHODS:
      Preoperative scalp EEG recordings with waking and sleep states were assessed in
      83 patients with TLE in whom localization of the epileptogenic zone was
      subsequently confirmed by successful surgical treatment (patient seizure-free >1
      year). RESULTS: The accuracy of EEG recordings for prediction of lateralization
      significantly changed from 51.8% during waking to 78.3% during sleep. After
      exclusion of patients who showed no discharges, the predictive value changed from
      74.1 to 86.7%. However, in patients in whom the waking scalp EEG lateralized
      incorrectly, no improvement in reliability was achieved by sleep recording.
      CONCLUSIONS: Our results suggest that IEDs occurring in non-REM sleep provide
      more accurate information for lateralization of epileptogenesis than do those
      occurring during waking. This gain of diagnostic information was obtained in
      patients who showed either bilateral or no discharges in waking records, because
      unilateral discharges arising de novo in sleep were always correctly
      lateralizing. On the other hand, in patients who showed unilateral discharges in
      the awake state, whether ipsilateral or contralateral to the epileptogenic zone,
      the findings were generally unchanged during sleep.

PMID- 9637606
TI  - Longitudinal quantitative hippocampal magnetic resonance imaging study of adults
      with newly diagnosed partial seizures: one-year follow-up results.
AB  - PURPOSE: We wished to establish whether hippocampal changes occur in 1 year in
      adults with newly diagnosed partial seizures and, if so, to identify possible
      causes and mechanisms. METHODS: Thirty-six adult patients with newly diagnosed
      partial seizures underwent a magnetic resonance imaging (MRI) scan of the brain
      including hippocampal volume and T2 relaxation time (HCT2) measurement and had a
      follow-up quantitative MRI scan approximately 1 year after the baseline MRI scan.
      RESULTS: At baseline, 4 patients (11%) had hippocampal sclerosis (HS), 4 (11%)
      had abnormalities other than HS, and 28 had a normal MRI scan (78%). Twenty-three
      patients (64%) had recurrent seizures in the period between the two MRI scans.
      One of the 4 patients with HS, who had daily seizures, had significantly
      increased HCT2 values on follow-up, possibly reflecting progressive hippocampal
      damage. None of the 32 patients with MRI findings other than HS at baseline
      progressed to HS on follow-up. However, 2 of the 32 patients had significant
      hippocampal changes, probably related to resolution of inflammatory swelling or
      edema after seizures were controlled. CONCLUSIONS: Subtle changes in hippocampi
      can occur in 1 year in adults with newly diagnosed partial seizures, which could
      be due to resolution of edema after seizure control or to hippocampal changes
      associated with frequent and daily seizures. Follow-up of the studied cohort for
      several years will be required to settle the question of whether progressive
      hippocampal damage occurs in temporal lobe epilepsy (TLE).

PMID- 9637607
TI  - Cerebellar changes in partial seizures: clinical correlations of quantitative
      SPECT and MRI analysis.
AB  - PURPOSE: To determine the frequency and patterns of periictal cerebellar
      hyperperfusion, whether it is associated with increased cerebellar atrophy, and
      whether cerebellar hyperperfusion and cerebellar atrophy are associated with
      predisposing clinical factors or with the outcome of epilepsy surgery. METHODS:
      Periictal and interictal SPECT scans and volumetric brain magnetic resonance
      imaging (MRI) were quantitatively analyzed in 54 consecutive patients with
      medically refractory partial epilepsy. Their histories were reviewed and their
      postsurgical outcomes assessed. RESULTS: Significant periictal cerebellar
      hyperperfusion was found in 26 (48.1%) patients, of whom 18 had CCH, two had
      homolateral cerebellar hyperperfusion (HCH), and six had symmetrical bilateral
      hyperperfusion (BCH). No relation found between the site of the SPECT seizure
      localization and the presence or type of cerebellar hyperperfusion. CCH was more
      common when the injected seizure involved unilateral clonic motor activity (p <
      0.05). A smaller MRI relative cerebellar volume (cerebellar volume/cerebral
      volume) was correlated with a greater seizure frequency (Rs = -0.30; p < 0.05)
      but not with the duration of epilepsy. There was no difference in the cerebellar
      volumes between the different patterns of cerebellar perfusion (p > 0.05).
      However, patients without a focal structural MRI lesion had significantly smaller
      cerebellar volumes (p < 0.05). In patients who underwent epilepsy surgery (n =
      31), there was a trend for those without excellent outcomes to have smaller
      relative cerebellar volumes than did those with excellent outcome (10.6 vs.
      11.8%; p = 0.08). CONCLUSIONS: Periictal changes in cerebellar perfusion,
      particularly CCH, are common in patients with intractable partial epilepsy.
      However, periictal hyperperfusion does not appear to be a major contributor to
      the development of cerebellar atrophy.

PMID- 9637608
TI  - Bilateral temporal hypometabolism in epilepsy.
AB  - PURPOSE: Positron emission tomography (PET) has proven useful in epilepsy surgery
      for its ability to identify unilateral temporal hypometabolism (UTH), which is
      predictive of good surgical outcome. The significance of bilateral temporal
      hypometabolism (BTH) is not known. METHODS: We identified all patients who had
      marked bilateral reduction in temporal lobe metabolism relative to the cerebellar
      hemispheres and compared their clinical features and treatment outcomes with
      those of control patients with UTH. RESULTS: BTH was evident in 10% of PET scans
      for epilepsy at our institution. We compared these patients with age-matched
      controls with UTH. The BTH patients had a higher percentage of generalized
      seizures; were more likely to have bilateral, diffuse or extratemporal seizure
      onsets; and had bilateral or diffuse magnetic resonance imaging (MRI) findings.
      UTH patients were more likely to have unilateral mesial temporal atrophy on MRI.
      Even when electrical seizure onsets were well localized, surgical outcomes were
      markedly worse in these patients than in controls. Medical treatment was also
      less successful. Social and cognitive functioning was worse in the BTH group. The
      only death occurred in the group with BTH. CONCLUSIONS: Patients with BTH have
      features distinct from those with UTH and have a worse prognosis for seizure
      remission after surgery.

PMID- 9637609
TI  - Myoclonic absence-like seizures and chromosome abnormality syndromes.
AB  - PURPOSE: We explored the relationship between myoclonic absence seizures (MAS)
      and underlying chromosome disorders. METHODS: Among 14 patients with MAS observed
      in three centers, 5 had typical cryptogenic myoclonic absence epilepsy (MAE), 2
      had MAS associated with other seizure types (1 with signs of a neuronal migration
      abnormality and 1 with signs of a metabolic disorder), and 7 had MAS, with or
      without other seizure types, complicating a chromosome abnormality syndrome-2
      with trisomy 12p, 4 with Angelman syndrome, and 1 with inv dup (15). RESULTS: In
      the 7 patients with chromosomopathy, MAS appeared at a mean age of 2.9 years
      (range 4 months to 6 years 6 months), had a duration of 4-20 s, and were
      accompanied by reduced awareness and rhythmic myoclonic jerks involving proximal
      limb muscles. Ictal EEG showed 2- to 3-Hz generalized spike-and-wave discharges.
      CONCLUSIONS: In these patients, MAS differed slightly from those of typical MAE:
      age of onset was earlier, absences were of shorter duration, and no clear
      increase in muscular tone was noted. Abnormal expression of genes codifying for
      the subfamily of K+ channels and for gamma-aminobutyric acid-3 subunit receptors
      (GABRB3), both located in the chromosome segments involved in the
      chromosomopathies presented by our patients, could be responsible for the same
      generalized seizure type. Chromosome analysis should be performed in patients
      with mental retardation and MAS, especially when the ictal pattern does not
      completely overlap that observed in MAE.

PMID- 9637610
TI  - Fixation-off and eyes closed catamenial generalized nonconvulsive status
      epilepticus with eyelid myoclonic jerks.
AB  - PURPOSE: Eyelid myoclonic jerks have been described in fixation-off-sensitive
      (FOS) epilepsy, but their relationship to nonconvulsive status epilepticus (NCSE)
      or to catamenial exacerbations is little reported. METHODS: We describe a woman
      of normal intelligence with catamenial periods of prolonged NCSE who exhibited
      various intra- and interseizure thresholds of polyspike suppression when her eyes
      were open, with particular visual inputs and with antiepileptic drug (AED)
      treatment. RESULTS: In one episode, on the first day of the woman's menstrual
      period, bursts of bilateral synchronous polyspike activity were briefly
      suppressed with visual fixation but were more lastingly suppressed after
      administration of lorazepam (LZP). During another period of NCSE, the SE was
      completely suppressed by visual fixation on objects and patterned checkerboard
      screens and by ocular convergence, was incompletely suppressed when her eyes were
      open in a dark room and when her eyes were open without visual fixation, but was
      not suppressed by mental activation alone. CONCLUSIONS: FOS polyspike bursts with
      eyelid myoclonic jerks may exhibit catamenial exacerbations, varying from
      completely suppressible with visual fixation to nonsuppressible during NCSE.
      These findings suggest an interplay between humoral factors, AEDs, and seizure
      threshold in this condition.

PMID- 9637611
TI  - Prolonged coma and severely attenuated EEG after a single seizure.
AB  - A 63-year-old woman presented with a comatose state after a fall. Results of
      cranial computed tomography (CT) and magnetic resonance imaging (MRI) scans were
      normal. An EEG recorded 5 h after admission was very severely attenuated and
      slowed. Consciousness and EEG were improved the next day. No cause was detected
      initially. After sleep deprivation, the patient had a generalized seizure
      followed by a similar coma and EEG. Even a single seizure may cause a prolonged
      coma with a very severely attenuated and slowed EEG.

PMID- 9637612
TI  - Nonconvulsive status epilepticus in two patients receiving tiagabine treatment.
AB  - In the course of an open study on the add-on treatment of tiagabine (TGB) in
      patients with localization-related epilepsy syndromes, 2 of 9 patients developed
      nonconvulsive status epilepticus (NCSE) with electroclinical features consistent
      with those of atypical absence seizures. One patient had never had atypical
      absence seizures before. In both cases, immediate discontinuation of TGB was
      followed by complete and sustained electroclinical remission; we suggest a
      possible causative role of TGB. This observation may be consistent with a
      paradoxical effect of TGB in selected cases. Possible risk factors and a
      pathophysiological hypothesis are discussed.

PMID- 9637613
TI  - The future of aneurysm surgery.

PMID- 9637614
TI  - The future of aneurysm surgery.

PMID- 9637615
TI  - The future of aneurysm surgery.

PMID- 9637616
TI  - The future of aneurysm surgery.

PMID- 9637617
TI  - The future of aneurysm surgery.

PMID- 9637618
TI  - Endoscopic transforaminal lumbar discectomy and reconfiguration: a postero
      lateral approach into the spinal canal.
AB  - BACKGROUND: In the past, minimally invasive procedures (chemonucleolysis, laser,
      automated percutaneous discectomy, percutaneous manual nucleotomy, arthroscopy)
      have been largely confined to intradiscal work. This study represents cases of
      working channel, transforaminal spinal endoscopy performed using an endoscope
      which, because of its small size and flexibility, can bend up to 90 degrees
      (depending on the guiding cannula), and pass completely through the foramen into
      the spinal canal (truly transforaminal, as opposed to just going through part of
      the foramen and into the disc), to directly remove free fragments and reconfigure
      disc, relieving root and dural displacement at all lumbar levels. METHODS: The
      records of 533 patients who had outpatient, minimally invasive operations
      performed over a 6-year period (ending in 1995) by this author were analyzed. Of
      these, 110 had small scope transforaminal procedures, forming the basis of this
      study. RESULTS: An independent observer followed the 110 patients who had
      endoscopic transforaminal procedures for 2 or more years. Using MacNab's
      criteria, the success rate (excellent or good) was 95% in the 75 patients with
      disc presenting lateral to the dura-"lateral presenting,"-and 83% in the 35
      patients not presenting disc for direct removal-"non-lateral presenting" (i.e.,
      dura in the pathway)-making an overall success rate of 91%. One patient who
      developed discitis was the only complication. CONCLUSION: Guideable endoscopes
      small enough to pass completely through the foramen allow percutaneous surgery to
      include non-contained disc herniations and even some migrated free fragments,
      depending on the location. The percutaneous transforaminal endoscopic technique
      can be an effective, safe approach for disc removal through the foramen,
      especially in cases where the disc presents itself for direct removal.

PMID- 9637619
TI  - Thoracic disc herniations: transthoracic, lateral, or posterolateral approach? A
      review.
AB  - BACKGROUND: The choice between transthoracic, lateral, and posterolateral
      approaches to excise thoracic disc herniations remains controversial. METHODS:
      The outcome of the three approaches was compared in seven of the authors' cases
      and in 324 other cases reported in the literature. RESULTS: Partial or total
      neurological recovery was found in 93% after a transthoracic procedure versus 87%
      after a posterolateral technique and 80% after a lateral approach (P < 0.05). A
      trend toward superior results after a transthoracic technique was also noted in
      subgroups of patients with radiculopathy, patients with intradural disc
      herniations, and patients with multiple lesions, although statistical
      significance was not reached. Pulmonary complications occurred in 7% of
      transthoracic techniques versus 5% in lateral and 0% in posterolateral techniques
      (p < 0.025). CONCLUSIONS: The transthoracic approach is recommended for all
      thoracic disc herniations below the T4 level except for patients with serious
      pulmonary compromise.

PMID- 9637620
TI  - Review: complications of surgery for thoracic disc disease.
AB  - BACKGROUND: Thoracic discectomy has evolved over the last 60 years from resection
      through standard laminectomy, to posterolateral procedures to open thoracotomy
      and finally thoracoscopy. Comparison of relative morbidity and mortality between
      these approaches is now possible. METHODS: Peer-reviewed publications reporting
      clinical data relating to thoracic discectomy, and which provided sufficient
      information to enable adequate assessment of mortality and morbidity were
      reviewed. These articles were determined via review of the results of MedLine
      searches and articles gathered through compilation of references from those
      articles. RESULTS: Articles reviewed spanned a period of over 60 years. Surgical
      procedures used for thoracic discectomy included laminectomy, pediculectomy,
      costotransversectomy, lateral extracavitary, transverse arthropediculectomy,
      anterolateral thoracotomy, and thoracoscopy. Complications included death,
      paralysis, paresis, loss of bowel and/or bladder control, pulmonary embolism,
      pneumonia, atelectasis, compression fracture, infection, pleural tear, bowel
      obstruction, and anesthesia dolorosa. Mortality dropped to nearly zero after
      development of anterior and posterolateral approaches. Morbidity seems relatively
      similar between most procedures other than laminectomy. Not enough procedures
      have been reported using thoracoscopy to adequately assess its morbidity.
      CONCLUSION: Comparison of relative rates of morbidity and mortality between
      surgical approaches to thoracic discectomy suggest that laminectomy does not
      provide adequate access for the safe removal of these lesions. Choice of approach
      among the alternatives should be based on the evacuation of the herniated
      fragment and experience of the surgeon. Thoracoscopy, although promising, has not
      had sufficient time for evaluation of morbidity to make definite statements
      regarding its safety.

PMID- 9637621
TI  - Management options in thoracolumbar burst fractures.
AB  - BACKGROUND: Both surgery and recumbency have been adopted in the treatment of
      spinal fractures. Herein we present the indications for each, and our experience
      with thoracolumbar junction (T12, L1 and L2) burst fractures. METHODS: Sixty
      eight patients with thoracolumbar burst fractures were treated operatively in 36
      cases, and nonoperatively in 32 with recumbency for 1-6 weeks. Treatment was
      based on clinical and radiological criteria. Eighty-one percent of the recumbency
      patients, but only 14% of the surgical patients were intact on admission.
      Patients were followed for a mean+/-SD of 9+/-10 months in the recumbency group,
      and 21+/-21 months in the surgical group. RESULTS: Neurological improvement and
      progressive angular deformity occurred in both groups. The cost of recumbency in
      our patients was nearly half that of those who required surgery, though the
      length of hospitalization between the two groups was similar at 1 month +/-2
      weeks. CONCLUSION: The above study emphasizes that the selection of operative
      versus nonoperative treatment in burst fractures should not be random but based
      on clinical as well as radiological criteria. Recumbency is favored in patients
      who are intact, with angular deformity less than 20 degrees , a residual spinal
      canal greater than 50% of normal, and an anterior body height exceeding 50% of
      the posterior height. Surgical intervention is generally indicated in patients
      with partial neurological deficit, and those with severe instability.

PMID- 9637622
TI  - Comparison of hydroxyapatite granules to autogenous bone graft in fusion cages in
      a goat model.
AB  - BACKGROUND: With the increased use of fusion cages to achieve lumbar
      intervertebral fusion, the question arises as to the potential for bone ingrowth
      from the host bone through the entire cage. Is it even necessary to have an
      autogenous graft to achieve total bone incorporation? METHODS: Nine adult male
      goats had fusion cages implanted into three vertebral bodies. The design was
      Surgical Dynamics/Ray Fusion Cage, measuring 21 mm x 14 mm. In each animal, one
      fusion cage was filled with autogenous graft, one with hydroxyapatite, porous
      granules, and the other with nonporous granules. Amount of new bone formation was
      determined by backscatter electron microscopy at 3 months post implantation in
      all animals. RESULTS: The histologic section shows that there was total
      incorporation in all specimens at 3 months. There was slightly more new bone
      (43%) with the nonporous granules compared with the porous granules (35%). The
      amount of residual void space was about the same in all specimens, indicating
      that the amount of new bone formation was similar and not statistically different
      in cages filled with hydroxyapatite granules versus granules of autogenous bone.
      CONCLUSION: This study confirms that total incorporation by ingrowth of new bone
      can be expected in fusion cages. The amount of ingrowth is about the same for
      autogenous graft versus hydroxyapatite granules. Apparently, it is not necessary
      to use bone graft to achieve successful bone incorporation if an acceptable
      biocompatable lattice, such as hydroxyapatite granules, is used.

PMID- 9637623
TI  - Fluorosis.

PMID- 9637624
TI  - Neurosurgery of the peripheral nervous system: the posterior interosseous nerve
      syndrome.

PMID- 9637625
TI  - Computed imaging-assisted stereotactic brain biopsy: a risk analysis of 225
      consecutive cases.
AB  - BACKGROUND: Treatment strategies for intracranial mass lesions are most effective
      when based upon histopathological diagnoses. Image-guided stereotaxy has provided
      the means to sample tissue from small or deeply seated intraparenchymal lesions
      with a relatively high degree of safety and accuracy. Although procedural
      complications are infrequent, devastating neurological sequelae may result from
      hemorrhage or direct trauma. This study was undertaken to identify factors that
      may confer an increased risk of morbidity from stereotactic brain biopsy.
      METHODS: Two hundred twenty-five consecutive computer-assisted stereotactic brain
      biopsy procedures were reviewed. Patient age averaged 47.4 years (range, 3-84
      years); gender ratio was approximately 2:1 (male:female). Pre-existing medical
      conditions were identified in nearly half of the cohort. 61.3% of biopsied
      lesions were lobar; the remainder (38.7%) were "deep-seated" (thalamus, basal
      ganglia, pineal, hypothalamus, cerebellum, brainstem). Glial tumors accounted for
      the majority (44.4%) of biopsied lesions; metastases (12.9%) and lymphoma (11.6%)
      were also relatively common. Demographical, anatomical, surgical, and
      histological data were compiled and putative risk factors for morbidity
      identified. These variables were then subjected to univariate and logistic
      regression analyses to determine their significance as independent predictors of
      operative risk. RESULTS: Twelve patients suffered complications as a consequence
      of the biopsy procedure (eight from hemorrhage, four from direct trauma). Major
      morbidity (hemiparesis, aphasia, obtundation) occurred in eight patients (3.6%).
      Three patients (1.3%) suffered minor morbidity (transient, mild neurological
      deficits). One operative fatality occurred (0.4%). An increased risk of morbidity
      was associated with the preoperative use of antiplatelet agents, chronic
      corticosteroids, deep-seated lesions, malignant gliomas, and a greater number of
      biopsy attempts (p < 0.05). Factors not conferring increased morbidity included
      gender, age, pre-existing illness, extracranial malignancy, cardiac disease,
      hypertension, diabetes, HIV status, and instrument used to procure the specimen.
      CONCLUSIONS: Complications arising from stereotactic brain biopsy are infrequent
      but can be disastrous. Operative risk is a function of several independent
      variables, including lesion properties (location, histology), preoperative
      pharmacological therapy (corticosteroids, antiplatelet agents), and operative
      technique. This analysis suggests that the morbidity of stereotactic brain biopsy
      may be minimized by risk factor modification.

PMID- 9637626
TI  - Correlations between brain tissue oxygen tension, carbon dioxide tension, pH, and
      cerebral blood flow--a better way of monitoring the severely injured brain?
AB  - BACKGROUND: The ideal method for monitoring the acutely injured brain would
      measure substrate delivery and brain function continuously, quantitatively, and
      sensitively. We have tested the hypothesis that brain PO2, pCO2, and pH, which
      can now be measured continuously using a single sensor, are valid indicators of
      regional cerebral blood flow (CBF) and oxidative metabolism, by measuring its
      product, brain pCO2. METHODS: Twenty-five patients (Glasgow Coma Score < or = 8)
      were studied. A Clark electrode, combined with a fiber optic system (Paratrend 7,
      Biomedical Sensors, Malvern, PA) was used to measure intraparenchymal brain PO2,
      pCO2, and pH. Data were averaged over a 1-h period before and after CBF studies.
      Regional CBF was measured around the probe, using stable xenon computed
      tomography. Regression analyses and Spearman Rank tests were used for data
      analysis. RESULTS: Regional CBF and mean brain PO2 were strongly correlated
      (r=0.74, p=0.0001). CBF values < 18 mL/100 g/min were all accompanied by brain
      PO2 < or = 26 mm Hg. The four patients with a brain PO2 < 18 mm Hg died. Brain
      pCO2 and pH, however, were not correlated with CBF (r=0.36, p=0.24 and r=0.30,
      p=0.43, respectively). CONCLUSIONS: Until recently, substrate supply to the
      severely injured brain could only be intermittently estimated by measuring CBF.
      The excellent intra-regional correlation between CBF and brain pO2, suggests that
      this method does allow continuous monitoring of true substrate delivery, and
      offers the prospect that measures to increase O2 delivery (e.g., increasing CBF,
      CPP, perfluorocarbons etc.) can be reliably tested by brain PO2 monitoring.

PMID- 9637627
TI  - Targeted studies as a learning tool in outcomes assessment.
AB  - Authors discuss the need for increased analytical skills in the current medical
      environment and suggest a method which combines the use of targeted studies and
      Internet communication as part of graduate medical education. Advantages of such
      a program include involvement of the private sector in clinical outcome studies,
      improvements in the design of clinical studies and publications and the early
      development of skills in interpreting and evaluating literature. A further goal
      would be the development of an understanding of the principles underlying, to the
      extent that it is possible, unbiased assessment of one's own clinical practices.

PMID- 9637628
TI  - Hemorrhagic lesions causing acute sensorineural hearing loss.

PMID- 9637629
TI  - Implications of evolving health care: changes for tertiary care specialties such
      as neurosurgery: practice, teaching, and research in the future in the academic
      setting.

PMID- 9637630
TI  - Omental transplantation.

PMID- 9637631
TI  - Bupivacaine in lumbar spine surgery.

PMID- 9637632
TI  - Fast track cardiac surgery pathways: early extubation, process of care, and cost
      containment.

PMID- 9637633
TI  - Laryngeal reflexes: exploring terra incognita.

PMID- 9637634
TI  - Halogenated anesthetics and the injured lung: clouds on the horizon?

PMID- 9637635
TI  - Do shorter-acting neuromuscular blocking drugs or opioids associate with reduced
      intensive care unit or hospital lengths of stay after coronary artery bypass
      grafting? CABG Clinical Benchmarking Data Base Participants.
AB  - BACKGROUND: The authors hypothesized that shorter-acting opioid and neuromuscular
      blocking drugs would be associated with reductions in duration of intubation,
      length of stay (LOS) in the intensive care unit (ICU) after tracheal extubation,
      or postoperative (exclusive of ICU) LOS, and that shorter durations of intubation
      would be associated with reduced ICU LOS after extubation and postoperative
      (exclusive of ICU) LOS. METHODS: One-thousand ninety-four patients undergoing
      primary coronary artery bypass graft surgery at 40 academic health centers were
      studied. Multiple patient-related factors were included in multivariate models
      for hypothesis testing. RESULTS: The duration of tracheal intubation, ICU LOS
      after extubation, and postoperative (exclusive of ICU) LOS all varied
      significantly by site. There was no difference between vecuronium and pancuronium
      in duration of intubation, ICU LOS after extubation, or postoperative (exclusive
      of ICU) LOS. Use of sufentanil rather than fentanyl was associated with a
      significant (P=0.045) reduction of 1.9 h (95% CI, 0.04 to 4.1 h) in duration of
      tracheal intubation but had no significant effect on ICU LOS after extubation,
      total ICU LOS, postoperative (exclusive of ICU) LOS, or total postoperative LOS.
      The authors' best model predicts a complex association between increasing
      duration of intubation and both ICU LOS after tracheal extubation and
      postoperative (exclusive of ICU) LOS, which was associated with an increase in
      those measures when duration of intubation exceeded 7.3 or 3 h, respectively.
      CONCLUSIONS: The LOS measures varied considerably among the institutions. Use of
      shorter-acting opioid and neuromuscular blocking drugs had no association with
      ICU LOS after tracheal extubation or with postoperative (exclusive of ICU) LOS.
      Only when the duration of intubation exceeded threshold values was it associated
      with increased LOS measures.

PMID- 9637636
TI  - Early extubation following cardiac surgery in a veterans population.
AB  - BACKGROUND: Early tracheal extubation is an important component of the "fast
      track" cardiac surgery pathway. Factors associated with time to extubation in the
      Department of Veterans Affairs (DVA) population are unknown. The authors
      determined associations of preoperative risk and intraoperative clinical process
      variables with time to extubation in this population. METHODS: Three hundred four
      consecutive patients undergoing coronary artery bypass graft, valve surgery, or
      both on a fast track clinical pathway between October 1, 1993 and September 30,
      1995 at a university-affiliated DVA medical center were studied retrospectively.
      After univariate screening of a battery of preoperative risk and intraoperative
      clinical process variables, stepwise logistic regression was used to determine
      associations with tracheal extubation < or = 10 h (early) or > 10 h (late) after
      surgery. Postoperative lengths of stay, complications, and 30-day and 6-month
      mortality rates were compared between the two groups. RESULTS: One hundred forty
      six patients (48.3%) were extubated early; one patient required emergent
      reintubation (0.7%). Of the preoperative risk variables considered, only age
      (odds ratio, 1.80 per 10-yr increment) and preoperative intraaortic balloon pump
      (odds ratio, 7.88) were multivariately associated with time to extubation (model
      R) ("late" association is indicated by an odds ratio >1.00; "early" association
      is indicated by an odds ratio <1.00). Entry of these risk variables into a second
      regression model, followed by univariately significant intraoperative clinical
      process variables, yielded the following associations (model R-P): age (odds
      ratio, 1.86 per 10-yr increment), sufentanil dose (odds ratio, 1.54 per 1
      microg/kg increment), major inotrope use (odds ratio, 5.73), platelet transfusion
      (odds ratio, 10.03), use of an arterial graft (odds ratio, 0.32), and fentanyl
      dose (odds ratio, 1.45 per 10-microg/kg increment). Time of arrival in the
      intensive care unit after surgery was also significant (odds ratio, 1.42 per 1-h
      increment). Intraoperative clinical process variables added significantly to
      model performance (P < 0.001 by the likelihood ratio test). CONCLUSIONS: In this
      population, early tracheal extubation was accomplished in 48% of patients.
      Intraoperative clinical process variables are important factors to be considered
      in the timing of postoperative extubation after fast track cardiac surgery.

PMID- 9637637
TI  - Upper airway reflexes during a combination of propofol and fentanyl anesthesia.
AB  - BACKGROUND: The effects of intravenous anesthetics on airway protective reflexes
      have not been fully explored. The purpose of the present study was to
      characterize respiratory and laryngeal responses to laryngeal irritation during
      increasing doses of fentanyl under propofol anesthesia. METHODS: Twenty-two
      female patients anesthetized with propofol and breathing through the laryngeal
      mask airway were randomly allocated to three groups: (1) eight patients who
      received cumulative total doses of 200 microg fentanyl given in the form of two
      doses of 50 microg and one dose of 100 microg spaced 6 min under mechanical
      controlled ventilation while end-tidal carbon dioxide tension (PCO2) was
      maintained at 38 mmHg (fentanyl-controlled ventilation group), (2) eight patients
      who received cumulative total doses of 200 microg fentanyl while breathing
      spontaneously while end-tidal PCO2 was allowed to increase spontaneously
      (fentanyl-spontaneous ventilation group), and (3) six spontaneously breathing
      patients who were anesthetized with propofol alone (propofol group). The
      laryngeal mucosa of each patient was stimulated by spraying the cord with
      distilled water, and the evoked responses were assessed by analyzing the
      respiratory variables and endoscopic images. RESULTS: Before administration of
      fentanyl, laryngeal stimulation caused vigorous reflex responses, such as
      expiration reflex spasmodic panting, cough reflex, and apnea with laryngospasm.
      Increasing doses of fentanyl reduced the incidences of all these responses,
      except for apnea with laryngospasm, in a dose-related manner in both the fentanyl
      controlled ventilation and the fentanyl-spontaneous ventilation groups. Detailed
      analysis of endoscopic images revealed several characteristics of laryngeal
      behavior during the airway reflex responses. CONCLUSION: Incremental doses of
      fentanyl depress airway reflex responses in a dose-related manner, except for
      apnea with laryngospasm.

PMID- 9637638
TI  - Intravenous remifentanil: placental transfer, maternal and neonatal effects.
AB  - BACKGROUND: Remifentanil has not been studied in obstetric patients. This study
      evaluates the placental transfer of remifentanil and the neonatal effects when
      administered as an intravenous infusion. METHODS: Nineteen parturients underwent
      nonemergent cesarean section with epidural anesthesia and received 0.1 microg kg(
      1) x min(-1) remifentanil intravenously, which was continued until skin closure.
      Maternal arterial (MA), umbilical arterial (UA), and umbilical venous (UV) blood
      samples were obtained at delivery for analysis of drug concentrations of
      remifentanil, its metabolite, and blood gases. Maternal vital signs were
      monitored continuously, and pain and sedation levels were assessed
      intermittently. Apgar scores were obtained at 1, 5, 10, and 20 min, and Neonatal
      and Adaptive Capacity Scores were noted 30 and 60 min after delivery. Parturients
      and newborns were observed for at least 24 h after surgery for side effects.
      RESULTS: The means and SDs of UV:MA and UA:UV ratios for remifentanil were 0.88+/
      0.78 and 0.29+/-0.07, respectively. Mean clearance was 93 ml x min(-1) kg(-1).
      The mean UV:MA and UA:MV ratios for remifentanil acid were 0.56+/-0.29 and 1.23+/
      0.89, respectively. The mean MA (remifentanil acid):MA (remifentanil) ratio was
      2.92+/-3.65. There were no adverse effects on the neonates, but there was a
      sedative effect and respiratory depressant effect on the mothers. CONCLUSIONS:
      Remifentanil crosses the placenta but appears to be rapidly metabolized,
      redistributed, or both. Maternal sedation and respiratory changes occur, but
      without adverse neonatal or maternal effects.

PMID- 9637639
TI  - Prophylactic angiotensin II infusion during spinal anesthesia for elective
      cesarean delivery.
AB  - BACKGROUND: Angiotensin II may prove useful in treating regional anesthesia
      induced hypotension in obstetric patients, because it causes less uterine
      vasoconstriction than do other vasoconstrictor drugs (such as phenylephrine).
      This study compared (1) maternal blood pressure and heart rate and (2) fetal
      status at delivery in parturients given either prophylactic angiotensin II or
      ephedrine infusion during spinal anesthesia for elective cesarean delivery.
      METHODS: Fifty-four women were randomized to receive either angiotensin II or
      ephedrine infusion intravenously during spinal anesthesia for elective cesarean
      section delivery. Simultaneous with subarachnoid injection, infusion of
      angiotensin II (2.5 microg/ml) or ephedrine (5 mg/ml) was initiated at 10 ng x
      kg(-1) x min(-1) and 50 microg x kg(-1) x min(-1), respectively. The rate of each
      infusion was adjusted to maintain maternal systolic blood pressure at 90-100% of
      baseline. RESULTS: Cumulative vasopressor doses (mean+/-SD) through 10, 20, and
      30 min were 150+/-100, 310+/-180, and 500+/-320 ng/kg in the angiotensin group
      and 480+/-210, 660+/-390, and 790+/-640 microg/kg in the ephedrine group.
      Maternal heart rate was significantly higher (P < 0.001) during vasopressor
      infusion in the ephedrine group than in the angiotensin group. Umbilical arterial
      and venous blood pH and base excess were all significantly higher (P < 0.05) in
      the angiotensin group than in the ephedrine group. CONCLUSIONS: Angiotensin II
      infusion maintained maternal systolic blood pressure during spinal anesthesia
      without increasing maternal heart rate or causing fetal acidosis.

PMID- 9637640
TI  - A comparison of the posterior versus lateral approaches to the block of the
      sciatic nerve in the popliteal fossa.
AB  - BACKGROUND: The main disadvantage of the posterior approach to the block of the
      sciatic nerve in the popliteal fossa (popliteal block [PB]) is the need to place
      the patient in the prone position. In this study, the authors examined the
      clinical utility of a recently described lateral approach to PB that is performed
      with the patient in the supine position, and they compared its ability to provide
      reliable surgical anesthesia with that of the posterior approach. METHODS: Fifty
      patients undergoing surgery of a lower extremity were randomized to receive the
      PB using either the lateral (n=25) or the posterior approach (n=25). With both
      techniques, 40 ml 1.5% alkalinized mepivacaine with 1:200,000 epinephrine were
      injected on successful nerve localization using low current output nerve
      stimulation. RESULTS: There were no differences in American Society of
      Anesthesiologists physical status or demographic data between the groups (ASA
      status, I-III; mean age, 50+/-15 yr; 27 men, 23 women). All patients had good
      intraoperative analgesia, except one in the lateral group, who reported pain
      outside the distribution of the sciatic nerve. CONCLUSIONS: Although blockade
      using the lateral approach took longer to accomplish, both techniques resulted in
      clinically acceptable anesthesia in the distribution of the sciatic nerve.

PMID- 9637641
TI  - Causes and prediction of maldistribution during continuous spinal anesthesia with
      isobaric or hyperbaric bupivacaine.
AB  - BACKGROUND: Many cases of cauda equina syndrome after maldistribution of local
      anesthetics during continuous spinal anesthesia have been reported. In
      experiments, a caudad route of catheter travel and the use of hyperbaric agents
      have been shown to induce these limited blocks. The aim of this clinical study
      was to verify this hypothesis and seek a predictive factor for the
      maldistribution of bupivacaine. METHOD: Continuous spinal anesthesia via a 19
      gauge end port spinal catheter was performed in 80 elderly patients randomly
      assigned to receive either isobaric or hyperbaric solutions. Successive
      injections of 2.5 mg bupivacaine were performed at 5-min intervals until a
      sensory level at or cranial to T8 was obtained. Maldistribution was defined by a
      sensory level caudal to T12 despite a total dose of 17.5 mg of either isobaric or
      hyperbaric bupivacaine. After surgery, all catheters were injected with contrast
      media and examined radiographically. RESULTS: The frequency of maldistribution
      was not significantly different in the isobaric and hyperbaric groups. A caudally
      oriented catheter tip was found to be a major cause of maldistribution (P < 10(
      5)). A thoracic sensory level could be reached in all patients presenting a
      limited block by simply changing the baricity of the bupivacaine, the position of
      the patient, or both. The sensory level obtained 10 min after the first injection
      of 2.5 mg isobaric or hyperbaric bupivacaine was found to be a predictive factor
      of maldistribution. CONCLUSIONS: Hyperbaric solutions do not appear to be a
      clinical factor in the development of limited block. The principle factor causing
      the maldistribution of bupivacaine is the caudal orientation of the tip of the
      end-hole catheter rather than its level or the route of catheter travel.

PMID- 9637642
TI  - Labor epidural analgesia without an intravascular "test dose".
AB  - BACKGROUND: This study prospectively evaluated the ability of aspiration to
      detect intravascular placement of multiple-orifice epidural catheters. METHODS:
      Multiple-orifice, 20-gauge epidural catheters were inserted in 1,029 laboring
      women. Catheters were observed and aspirated for blood or cerebrospinal fluid
      before they were tested with 2 ml local anesthetic. If the results of this test
      were negative (no spinal anesthesia), the authors induced and maintained labor
      analgesia with a dilute local anesthetic and opioid solution. Patients with
      bilateral sensory change and effective labor analgesia had a "positive" epidural
      catheter. Women with unilateral block, inadequate analgesia despite some sensory
      change or those who delivered before being adequately assessed had "equivocal"
      catheters. Patients with neither analgesia nor sensory change had "negative"
      catheters. RESULTS: Aspiration and observation identified 60 intravenously placed
      catheters. Six catheters, which were placed initially in a blood vessel, were
      withdrawn until aspiration was negative, and then the anesthetic was infused.
      Four of these catheters were positive and two were still positioned
      intravascularly. Two other catheters may have been intravenously placed despite
      negative results of aspiration. The incidence of false-negative results of
      aspiration was 0 to 2 of 1,085 (upper limit of 95% CI, 0.2% to 0.4%). No patient
      showed any signs or symptoms of local anesthetic toxicity. CONCLUSIONS: Under the
      conditions of this study, which include using multiple-orifice catheters and
      dilute solutions of local anesthetic and opioid, aspiration and incremental drug
      injection alone safeguard against the risks of intravenously positioned local
      anesthetics. These results should not be extrapolated to other clinical settings
      without further study.

PMID- 9637643
TI  - Treatment of incomplete analgesia after placement of an epidural catheter and
      administration of local anesthetic for women in labor.
AB  - BACKGROUND: Approximately 15% of women still have pain after placement of an
      epidural catheter and administration of local anesthetic for labor analgesia. Two
      techniques frequently used to treat this pain were compared: (1) withdrawal of
      the catheter 1 cm and repeated dosing with additional local anesthetic, and (2)
      repeated dosing with additional local anesthetic without any catheter
      manipulation. METHODS: Fifteen minutes after placement of a multiple-orifice
      epidural catheter 5 cm into the epidural space and administration of 13 ml 0.25%
      bupivacaine to the parturient in labor, the adequacy of analgesia was assessed.
      All women who had incomplete analgesia were randomized (first intervention) to
      receive an additional 5 ml 0.25% bupivacaine (local-anestheticonly group) or to
      receive 5 ml 0.25% bupivacaine after first withdrawing the epidural catheter 1 cm
      (catheter-manipulation group). If after 15 min the woman still had pain, then
      (second intervention) the catheter was withdrawn 1 cm and an additional 5 ml
      0.25% bupivacaine was administered to the local-anesthetic-only group, whereas 5
      ml 0.25% bupivacaine was given to the catheter-manipulation group without further
      catheter manipulation. The success rate of the second intervention was assessed
      15 min later. RESULTS: Seventy-eight women were enrolled in the study, 39 to each
      group. In the local-anesthetic-only group, 29 (74%) women were successfully
      treated with the first intervention and the remaining 10 (100%) were successfully
      treated with the second intervention. In the catheter-manipulation group, 30
      (77%) were successfully treated with the first intervention and 7 (100%; 2
      patients were not studied because of investigator error) were successfully
      treated with the second intervention (P=NS). CONCLUSIONS: Administration of
      additional local anesthetic without first withdrawing the epidural catheter will
      effectively treat most women for whom analgesia is incomplete after the placement
      of an epidural catheter during labor.

PMID- 9637644
TI  - Effects of oral clonidine on heart rate changes after neostigmine-atropine
      administration.
AB  - BACKGROUND: Clonidine reduces heart rate (HR) responses to atropine, whereas
      neostigmine causes bradycardia. This study was designed to determine whether
      clonidine premedication would reduce tachycardia after neostigmine-atropine
      administration. METHODS: Fifty adult patients without cardiovascular disorders
      who were scheduled for elective surgeries were randomly assigned to receive
      approximately 5 microg/kg (oral clonidine clonidine group, n=25) or no clonidine
      (control group, n=25) 90 min before induction of general anesthesia. After
      tracheal intubation, anesthesia was maintained with N2O and 12% isoflurane in
      oxygen while patients were paralyzed with vecuronium and mechanically ventilated.
      When surgeries were completed, adequate spontaneous respiration, responses to
      verbal commands, and sustained tetanus by stimulating the ulnar nerve were
      confirmed, and patients' tracheas were extubated. Then a mixture of 0.05 mg/kg
      neostigmine and 0.02 mg/kg atropine was administered intravenously over 20 s
      under stable hemodynamic condition (systolic blood pressure and HR within +/-5%
      of preceding values), and blood pressure and HR were measured noninvasively at 1
      min intervals for 10 min. RESULTS: Increases in HR in the clonidine group were
      significantly less 1-4 min after neostigmine--atropine injections compared with
      HR values in the control group. A maximum increase in HR of the clonidine group
      was also significantly less than the control group (15+/-7 vs. 23+/-10 beats/min;
      means+/-SD), whereas absolute values of mean blood pressure were similar. Severe
      bradycardia (HR < 50 beats/min) developed in no patients in either group.
      CONCLUSIONS: Premedication with 5 microg/kg oral clonidine attenuates the initial
      increases in HR without subsequent decreases in HR.

PMID- 9637645
TI  - Tissue heat content and distribution during and after cardiopulmonary bypass at
      31 degrees C and 27 degrees C.
AB  - BACKGROUND: Afterdrop following cardiopulmonary bypass results from
      redistribution of body heat to inadequately warmed peripheral tissues. However,
      the distribution of heat between the thermal compartments and the extent to which
      core-to-peripheral redistribution contributes to post-bypass hypothermia remains
      unknown. METHODS: Patients were cooled during cardiopulmonary bypass to
      nasopharyngeal temperatures near 31 degrees C (n=8) or 27 degrees C (n=8) and
      subsequently rewarmed by the bypass heat exchanger to approximately 37.5 degrees
      C. A nasopharyngeal probe evaluated core (trunk and head) temperature and heat
      content. Peripheral compartment (arm and leg) temperature and heat content were
      estimated using fourth-order regressions and integration over volume from 19
      intramuscular needle thermocouples, 10 skin temperatures, and "deep" foot
      temperature. RESULTS: In the 31 degrees C group, the average peripheral tissue
      temperature decreased to 31.9+/-1.4 degrees C (means+/-SD) and subsequently
      increased to 34+/-1.4 degrees C at the end of bypass. The core-to-peripheral
      tissue temperature gradient was 3.5+/-1.8 degrees C at the end of rewarming, and
      the afterdrop was 1.5+/-0.4 degrees C. Total body heat content decreased 231+/-93
      kcal. During pump rewarming, the peripheral heat content increased to 7+/-27 kcal
      below precooling values, whereas the core heat content increased to 94+/-33 kcal
      above precooling values. Body heat content at the end of rewarming was thus 87+/
      42 kcal more than at the onset of cooling. In the 27 degrees C group, the average
      peripheral tissue temperature decreased to a minimum of 29.8 +/-1.7 degrees C and
      subsequently increased to 32.8+/-2.1 degrees C at the end of bypass. The core-to
      peripheral tissue temperature gradient was 4.6+/-1.9 degrees C at the end of
      rewarming, and the afterdrop was 2.3+/-0.9 degrees C. Total body heat content
      decreased 419+/-49 kcal. During pump rewarming, core heat content increased to
      66+/-23 kcal above precooling values, whereas peripheral heat content remained
      70+/-42 kcal below precooling values. Body heat content at the end of rewarming
      was thus 4+/-52 kcal less than at the onset of cooling. CONCLUSIONS: Peripheral
      tissues failed to fully rewarm by the end of bypass in the patients in the 27
      degrees C group, and the afterdrop was 2.3+/-0.9 degrees C. Peripheral tissues
      rewarmed better in the patients in the 31 degrees C group, and the afterdrop was
      only 1.5+/-0.4 degrees C.

PMID- 9637646
TI  - Epidural fentanyl produces labor analgesia by a spinal mechanism.
AB  - BACKGROUND: The purpose of this study was to determine if epidural fentanyl
      produces analgesia in laboring patients by a primary spinal or supraspinal
      action. METHODS: Fifty-four parturients were randomized to receive epidural
      0.125% bupivacaine plus one of three treatments: epidural saline-intravenous
      saline, epidural fentanyl (20 microg/h)-intravenous saline, or epidural saline
      intravenous fentanyl (20 microg/h). The study treatments were administered by
      continuous infusion, whereas epidural bupivacaine use was patient controlled.
      RESULTS: Epidural bupivacaine use was significantly reduced by epidural (11.5+/
      4.6 ml/h) but not by intravenous fentanyl (15.9+/-4.5 ml/h) compared with saline
      control (16+/-5.9 ml/ h). Analgesia characteristics and side effects were similar
      among groups. CONCLUSIONS: Low-dose epidural infusions of fentanyl produce labor
      analgesia by a primary spinal action.

PMID- 9637647
TI  - Desflurane increases pulmonary alveolar-capillary membrane permeability after
      aortic occlusion-reperfusion in rabbits: evidence of oxidant-mediated lung
      injury.
AB  - BACKGROUND: Pulmonary injury occurs after vascular surgery, with xanthine oxidase
      (an oxidant generator) released from reperfusing liver and intestines mediating a
      significant component of this injury. Because halogenated anesthetics have been
      observed to enhance oxidant-mediated injury in vitro, the authors hypothesized
      that desflurane would increase alveolar-capillary membrane permeability mediated
      by circulating xanthine oxidase after thoracic occlusion and reperfusion.
      METHODS: Rabbits were assigned to one of five groups: aorta occlusion groups
      administered desflurane (n=14), desflurane and tungstate (xanthine oxidase
      inactivator, n=12), fentanyl plus droperidol (n=13), and two sham-operated groups
      (desflurane, n=7 and fentanyl plus droperidol, n=7). Aortic occlusion was
      maintained for 45 min with a balloon catheter, followed by 3 h of reperfusion.
      Alveolar-capillary membrane permeability was assessed by measurement of
      bronchoalveolar lavage fluid protein. Xanthine oxidase activity was determined in
      plasma and lung tissue. Ascorbic acid content (an antioxidant) was determined in
      lung tissue. RESULTS: Desflurane was associated with significantly increased
      alveolar-capillary membrane permeability after aortic occlusion-reperfusion when
      compared with the fentanyl plus droperidol anesthesia or sham-operated groups (P
      < 0.05). Inactivation of xanthine oxidase abrogated the alveolar-capillary
      membrane compromise associated with desflurane. Although significantly greater
      than for sham-operated animals, plasma xanthine oxidase activities released after
      aortic occlusion-reperfusion were not different between the two anesthetics.
      There were no anesthetic-associated differences in lung tissue xanthine oxidase
      activity. However, desflurane anesthesia resulted in a significant reduction in
      lung ascorbic acid after aortic occlusion-reperfusion compared with the sham
      operated animals. CONCLUSIONS: Desflurane anesthesia increased xanthine oxidase
      dependent alveolar-capillary membrane compromise after aortic occlusion
      reperfusion in concert with depletion of a key tissue antioxidant.

PMID- 9637648
TI  - Nonanesthetic volatile drugs obey the Meyer-Overton correlation in two molecular
      protein site models.
AB  - BACKGROUND: Nonanesthetic volatile compounds fail to inhibit movement in response
      to noxious stimulation at concentrations predicted to induce anesthesia from
      their oil-water partitioning. Thus they represent tools to determine whether
      molecular models behave like the targets that mediate in vivo anesthetic actions.
      The effects of volatile anesthetics and nonanesthetics were examined in two
      experimental models in which anesthetics interact directly with proteins: the
      pore of the nicotinic acetylcholine receptor and human serum albumin. METHODS:
      Wild-type mouse muscle nicotinic receptors and receptors containing pore
      mutations (alphaS252I + betaT263I) were studied electrophysiologically in
      membrane patches from Xenopus oocytes. Patch currents evoked by brief pulses of
      acetylcholine were measured in the presence of enflurane and two nonanesthetics,
      1,2-dichlorohexafluorocyclobutane and 2,3-dichlorooctafluorobutane. Nonanesthetic
      interactions with human serum album were assessed by quenching of intrinsic
      protein fluorescence. RESULTS: Both anesthetic and nonanesthetic volatile
      compounds inhibited wild-type and alphaS252I + betaT263I mutant nicotinic
      channels but displayed different selectivity for open versus resting receptor
      states. Median inhibitory concentrations (IC50s) in wild-type nicotinic receptors
      were 870+/-20 microM for enflurane, 37+/-3 microM for 1,2
      dichlorohexafluorocylcobutane, and 11.3+/-5.6 microM for 2,3
      dichlorooctafluorobutane. For all three drugs, ratios of wild-type IC50s to
      mutant IC50mut ranged from 7-10, and ratios of wild-type IC50s to predicted
      anesthetic median effective concentrations (EC50s) ranged from 1.8-2.3. 1,2
      Dichlorohexafluorocyclobutane quenched human serum albumin with an apparent
      dissociation constant (Kd) of 160+/-11 microM. The ratios of dissociation
      constants to predicted EC50s for the nonanesthetics were within a factor of two
      of the dissociation constant:EC50 ratios calculated for halothane and chloroform
      from previous published results. CONCLUSIONS: In two models in which anesthetics
      bind to protein sites, both anesthetic and nonanesthetic volatile drugs cause
      similar steady state effects with potencies that are predicted by hydrophobicity.
      These protein sites do not sterically discriminate between anesthetic and
      nonanesthetic drugs. However, differential state-selective actions on ion channel
      targets may underlie the distinct in vivo effects of anesthetics and
      nonanesthetics.

PMID- 9637649
TI  - The effects of extracellular pH with and without bicarbonate on intracellular
      procaine concentrations and anesthetic effects in crayfish giant axons.
AB  - BACKGROUND: The potentiating effect of sodium bicarbonate on local anesthetic
      action is attributed to two mechanisms: (1) an increase in the un-ionized local
      anesthetic due to extracellular alkalinization, and (2) an accelerated conversion
      of local anesthetic from un-ionized to ionized form with intracellular
      acidification caused by bicarbonate. To evaluate these hypotheses, the
      intracellular pH, intracellular ionized procaine concentration, and evoked action
      potentials were measured in crayfish giant axons. METHODS: In all measurements,
      axon preparations from crayfish were perfused extracellularly for 15 min with
      either bicarbonate-containing solution at pH 7.6 (bicarb/7.6) or bicarbonate-free
      solution at pH 7.6 (nonbicarb/7.6) or pH 8.0 (nonbicarb/8.0). Intracellular pH
      was measured using a pH-sensitive microelectrode. Intracellular anesthetic
      concentration was measured using a specially designed procaine-sensitive
      microelectrode with each of three solutions containing 1 mM procaine
      hydrochloride. Membrane potential was measured and, as an index of anesthetic
      action, the dV/dt of evoked action potential was calculated during perfusion with
      procaine. RESULTS: Mean intracellular pH was significantly lower in the
      bicarb/7.6 (7.16+/-0.07) group than in the nonbicarb/7.6 (7.33+/-0.09) and
      nonbicarb/8.0 (7.33+/-0.12) groups (P < 0.01). The mean intracellular ionized
      procaine concentration was significantly higher in the bicarb/7.6 (0.53+/-0.08
      mM; P < 0.05) and nonbicarb/8.0 (0.58+/-0.13 mM; P < 0.01) than in nonbicarb/7.6
      (0.32+/-0.14 mM) group but did not differ between the bicarb/7.6 and
      nonbicarb/8.0 groups. The mean percentage decrease in dV/dtmax was approximately
      coincident with the mean intracellular procaine concentration in each solution.
      CONCLUSION: The presence of bicarbonate or extracellular alkalinization increased
      the intracellular concentration of ionized procaine and the anesthetic effect.

PMID- 9637650
TI  - The effects of epidural morphine on cardiac and renal sympathetic nerve activity
      in alpha-chloralose-anesthetized cats.
AB  - BACKGROUND: Epidural morphine yields postoperative pain relief and hemodynamic
      stability. However, the effects of epidural morphine on sympathetic tone are
      unclear. This study was designed to elucidate the effects of epidural morphine on
      cardiac (CSNA) and renal (RSNA) sympathetic nerve activity by direct measurement
      in anesthetized cats. METHODS: Thirty mongrel cats anesthetized with alpha
      chloralose were randomly assigned to one of the following five groups: control
      (0.2 ml/kg thoracic epidural normal saline; n=5); thoracic epidural morphine
      (n=9); lumbar epidural morphine (n=6); vagotomized, sinoaortic denervated,
      thoracic epidural morphine (n=5); or intravenous morphine (n=5). Mean arterial
      pressure (MAP), heart rate (HR), CSNA, and RSNA were measured 0, 15, 30, 60, 90,
      and 120 min after saline or morphine (200 microg/kg) administration and 15 min
      after reversal with 200 microg naloxone given intravenously. RESULTS: In the
      control group, no changes in measured variables were found after either thoracic
      epidural saline or intravenous naloxone. Thoracic and lumbar epidural morphine
      both significantly reduced MAP, HR, CSNA, and RSNA 30 through 120 min after
      morphine administration (P < 0.05). These changes were reversed by intravenous
      naloxone. Changes after thoracic epidural morphine administration in vagotomized,
      baroreceptor-denervated cats were similar to those in intact cats. Intravenous
      morphine produced no significant changes except for a decrease in MAP, which was
      reversed by intravenous naloxone. CONCLUSION: In contrast to intravenous
      morphine, thoracic and lumbar epidural morphine both inhibited cardiac and renal
      sympathetic nerve activity and consequently reduced MAP and HR in alpha
      chloralose anesthetized cats.

PMID- 9637651
TI  - Effect of propofol on norepinephrine-induced increases in [Ca2+]i and force in
      smooth muscle of the rabbit mesenteric resistance artery.
AB  - BACKGROUND: Propofol (2,6-diisopropylphenol) possesses vasodilating activity in
      vivo and in vitro. The propofol-induced relaxation of agonist-induced
      contractions in small resistance arteries has not been clarified. METHODS: The
      effect of propofol was examined on the contractions induced by norepinephrine and
      high K+ in endothelium-denuded rabbit mesenteric resistance artery in vitro. The
      effects of propofol on the [Ca2+]i mobilization induced by norepinephrine and
      high K+ were studied by simultaneous measurement of [Ca2+]i using Fura 2 and
      isometric force in ryanodine-treated strips. RESULTS: Propofol attenuated the
      contractions induced by high K+ and norepinephrine, the effect being greater on
      the high K+-induced contraction than on the norepinephrine-induced contraction.
      In Ca2+-free solution, norepinephrine produced a transient contraction resulting
      from the release of Ca2+ from storage sites that propofol attenuated. In
      ryanodine-treated strips, propofol increased the resting [Ca2+]i but attenuated
      the increases in [Ca2+]i and force induced by both high K+ and norepinephrine. In
      the presence of nicardipine, propofol had no inhibitory action on the residual
      norepinephrine-induced [Ca2+]i increase, whereas it still modestly increased
      resting [Ca2+]i, as in the absence of nicardipine. CONCLUSIONS: In smooth muscle
      of the rabbit mesenteric resistance artery, propofol attenuates norepinephrine
      induced contractions due to an inhibition both of Ca2+ release and of Ca2+ influx
      through L-type Ca2+ channels. Propofol also increased resting [Ca2+]i, possibly
      as a result of an inhibition of [Ca2+]i removal mechanisms. These results may
      explain in part the variety of actions seen with propofol in various types of
      vascular smooth muscle.

PMID- 9637652
TI  - In vitro hypothermia enhances platelet GPIIb-IIIa activation and P-selectin
      expression.
AB  - BACKGROUND: A clinical bleeding diathesis is associated with hypothermia.
      Inhibition of platelet reactivity is the purported cause of this coagulopathy
      despite inconsistent evidence to support this hypothesis. To clarify the effect
      of temperature on intrinsic platelet function, platelet GPllb-IIIa activation and
      P-selectin expression were assessed under normothermic and hypothermic conditions
      in vitro. METHODS: Blood was obtained by venipuncture from healthy volunteers.
      Platelet activation was assessed by aggregometry and by cytometric analysis of
      platelet binding of fibrinogen, PAC-1, and P-selectin antibodies. Measurements
      were made at normothermia (37 degrees C), moderate hypothermia (33 degrees C),
      and profound hypothermia (22 degrees C) after stimulating samples with adenosine
      diphosphate (ADP), collagen, or thrombin receptor activating peptide. RESULTS:
      Agonist-induced platelet aggregation and fibrinogen binding were significantly
      greater at 22 degrees C and 33 degrees C than at 37 degrees C. Platelet
      fibrinogen binding values to 20 micro M ADP were 23,400, 14,300, and 9,700
      molecules/platelet at 22 degrees C, 33 degrees C, and 37 degrees C, respectively.
      The aggregation responses of platelets that were cooled and rewarmed were
      indistinguishable from those of platelets maintained at 37 degrees C throughout
      the study. Platelet binding of PAC-1 and P-selectin antibodies was greater under
      hypothermic conditions. CONCLUSIONS: Aggregation, fibrinogen binding, PAC-1
      binding, and P-selectin antibody binding studies showed that platelet GPIIb-IIIa
      activation and alpha-granule release were enhanced at hypothermic temperatures.
      Thus hypothermia appears to increase the ability of platelets to respond to
      activating stimuli. The coagulopathy associated with hypothermia is not likely to
      be the result of an intrinsic defect in platelet function.

PMID- 9637653
TI  - Rebound swelling of astroglial cells exposed to hypertonic mannitol.
AB  - BACKGROUND: Mannitol is widely used in anesthesia and critical care medicine.
      Although its clinical effects were originally attributed to osmotic dehydration
      of brain cells, other mechanisms have also been proposed. Osmotic dehydration of
      astroglial cells is opposed by powerful volume-regulating mechanisms that involve
      inward transport of electrolytes. These mechanisms have been studied previously
      by exposing cells to hypertonic saline gradients. Because of its potential
      clinical relevance, the volume response of astroglial cells exposed to hypertonic
      mannitol was investigated. METHODS: Rat C6 glioma cells were cultured to
      confluence, and their volume behavior was observed by laser light scattering.
      After equilibration at physiologic temperature and pH, cells were abruptly
      exposed to hypertonic mannitol solutions. In separate experiments, C6 cells were
      exposed to hypertonic solutions containing radiolabeled mannitol, and its
      cellular uptake was determined. RESULTS: Hypertonic mannitol exposure produced
      initial cell shrinkage followed by rapid volume recovery and rebound swelling.
      The rebound swelling was similar in magnitude to the initial maximal shrinkage.
      For +40 mOsm and +70 mOsm mannitol challenges, mean volume recovery was 184+/-31%
      and 227+/-62%, respectively (where full recovery to baseline volume = 100%).
      Rebound swelling was substantially inhibited by furosemide. When exposed to
      mannitol in varying concentrations, uptake was linear, ranging from 82+/-7
      nmol/mg to 406+/-26 nmol/mg protein. After 5 min, estimated intracellular
      concentrations of mannitol were similar to extracellular concentrations.
      CONCLUSIONS: Unlike hypertonic saline, hypertonic mannitol exposure produces
      rebound cell swelling. Cellular penetration of mannitol appears to account for
      much of this phenomenon. The clinical implications of these observations remain
      to be determined.

PMID- 9637654
TI  - Effects of small concentrations of volatile anesthetics on action potential
      firing of neocortical neurons in vitro.
AB  - BACKGROUND: Volatile general anesthetics depress neuronal activity in the
      mammalian central nervous system and enhance inhibitory Cl- currents flowing
      across the gamma-aminobutyric acid A (GABA(A)) receptor-ion channel complex. The
      extent to which an increase in GABA(A)-mediated synaptic inhibition contributes
      to the decrease in neuronal firing must be determined, because many further
      effects of these agents have been reported on the molecular level. METHODS: The
      actions of halothane, isoflurane, and enflurane on the firing patterns of single
      neurons were investigated by extracellular recordings in organotypic slice
      cultures derived from the rat neocortex. RESULTS: Volatile anesthetics depressed
      spontaneous action potential firing of neocortical neurons in a concentration
      dependent manner. The estimated median effective concentration (EC50) values were
      about one half the EC50 values for general anesthesia. In the presence of the
      GABA(A) antagonist bicuculline (20 microM), the effectiveness of halothane,
      isoflurane, and enflurane in reducing the discharge rates were diminished by 48
      65%, indicating that these drugs act via the GABA(A) receptor. CONCLUSIONS:
      Together with recent investigations, our results provide evidence that halothane,
      isoflurane, and enflurane reduced spontaneous action potential firing of
      neocortical neurons in cultured brain slices mainly by increasing GABA(A)
      mediated synaptic inhibition. At concentrations, approximately one half the EC50
      for general anesthesia, volatile anesthetics increased overall GABA(A)-mediated
      synaptic inhibition about twofold, thus decreasing spontaneous action potential
      firing by half.

PMID- 9637655
TI  - Halothane decreases Na,K-ATPase, and Na channel activity in alveolar type II
      cells.
AB  - BACKGROUND: Halothane alters surfactant biosynthesis and metabolism of alveolar
      type II cells. In addition to synthesizing surfactant, alveolar type II cells
      actively transport sodium (Na) from the alveolar space to the interstitium. Na
      enters the cells through amiloride-sensitive Na channels or Na cotransporters and
      is extruded by a Na pump. The purpose of this study was to examine the effects of
      halothane on Na transport activities. METHODS: Epithelial type II cells from
      adult rat lungs were exposed to halothane concentrations of 1, 2, and 4% from 0.5
      4 h. In some experiments, cells that were exposed to 1% halothane for 1 h were
      allowed to recover after replacement of the medium for 15 and 30 min. Na
      transport was then evaluated by direct measurement of radiolabeled ions uptake.
      In addition, the effects of halothane were assessed in the absence of
      extracellular calcium (Ca) with or without 1,2-bis(2-aminophenoxy)ethane
      N,N,N',N'-tetraacetic acid, an intracellular Ca chelating agent. RESULTS:
      Exposure of epithelial type II cells to halothane reduced the activity of sodium,
      potassium-adenosine triphosphatase, and amiloride-sensitive Na channels, whereas
      Na cotransporters were unchanged. The decrease in sodium, potassium-adenosine
      triphosphatase activity was maximal for 30 min of exposure and reached 50, 42,
      and 56% for halothane concentrations of 1, 2, and 4%, respectively, and did not
      change for longer exposure times. This effect was not prevented by either the
      absence of extracellular Ca or 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'
      tetraacetic acid pretreatment. Exposure for 45 min to 1% halothane also decreased
      Na channel activity by 46%. These effects were completely reversible after 30 min
      of recovery. CONCLUSIONS: Sodium, potassium-adenosine triphosphatase, and
      amiloride-sensitive Na channel activities are impaired by halothane in alveolar
      type II cells in vitro. This inhibition could reduce transepithelial Na
      transport.

PMID- 9637656
TI  - Cerebrovascular relaxation responses to endothelium-dependent and -independent
      vasodilators after normothermic and hypothermic cardiopulmonary bypass in the
      rabbit.
AB  - BACKGROUND: Cardiopulmonary bypass causes activation of leukocytes and increased
      concentrations of proinflammatory mediators, which may result in endothelial
      dysfunction. Because hypothermia attenuates many inflammatory processes, the
      authors hypothesized that hypothermic cardiopulmonary bypass would be associated
      with better endothelial function than normothermic cardiopulmonary bypass.
      METHODS: Isoflurane-anesthetized New Zealand White rabbits were randomized to
      undergo 90 min of either normothermic (37 degrees C, n=9) or hypothermic (27
      degrees C, n=9) cardiopulmonary bypass with terminal rewarming. A third group
      served as anesthetized normothermic non-cardiopulmonary bypass surgical controls
      (n=8). Basilar artery and descending thoracic aorta were isolated from each
      animal. In vitro vessel relaxation responses to increasing concentrations of
      acetylcholine (which induces endothelial release of nitric oxide) and
      nitroprusside (which provides exogenous nitric oxide) were measured in
      phenylephrine-precontracted vessel rings. RESULTS: There were no differences in
      vessel relaxation responses between normothermic and hypothermic cardiopulmonary
      bypass groups in basilar artery or aorta. In contrast, basilar arteries from non
      cardiopulmonary bypass controls had increased relaxation responses to both
      acetylcholine (P=0.004) and nitroprusside (P=0.031) compared with the pooled
      cardiopulmonary bypass animal data. CONCLUSIONS: The authors observed no
      differences in endothelial or vascular smooth muscle function between
      normothermic and hypothermic cardiopulmonary bypass groups. Compared with non
      cardiopulmonary bypass controls, cardiopulmonary bypass appeared to decrease
      basilar artery smooth muscle relaxation in response to endogenous and exogenous
      nitric oxide.

PMID- 9637657
TI  - Role of the renal cysteine conjugate beta-lyase pathway in inhaled compound A
      nephrotoxicity in rats.
AB  - BACKGROUND: The sevoflurane degradation product compound A is nephrotoxic in rats
      and undergoes metabolism to glutathione and cysteine S-conjugates, with further
      metabolism by renal cysteine conjugate beta-lyase to reactive intermediates.
      Evidence suggests that toxicity is mediated by renal uptake of compound A S
      conjugates and metabolism by beta-lyase. Previously, inhibitors of the beta-lyase
      pathway (aminooxyacetic acid and probenecid) diminished the nephrotoxicity of
      intraperitoneal compound A. This investigation determined inhibitor effects on
      the toxicity of inhaled compound A. METHODS: Fischer 344 rats underwent 3 h of
      nose-only exposure to compound A (0-220 ppm in initial dose-response experiments
      and 100-109 ppm in subsequent inhibitor experiments). The inhibitors (and
      targets) were probenecid (renal organic anion transport mediating S-conjugate
      uptake), acivicin (gamma-glutamyl transferase), aminooxyacetic acid (renal beta
      lyase), and aminobenzotriazole (cytochrome P450). Urine was collected for 24 h,
      and the animals were killed. Nephrotoxicity was assessed by histology and
      biochemical markers (serum BUN and creatinine; urine volume; and excretion of
      protein, glucose, and alpha-glutathione-S-transferase, a predominantly proximal
      tubular cell protein). RESULTS: Compound A caused dose-related proximal tubular
      cell necrosis, diuresis, proteinuria, glucosuria, and increased alpha-glutathione
      S-transferase excretion. The threshold for toxicity was 98-109 ppm (294-327 ppm
      h). Probenecid diminished (P < 0.05) compound A-induced glucosuria and excretion
      of alpha-glutathione-S-transferase and completely prevented necrosis.
      Aminooxyacetic acid diminished compound A-dependent proteinuria and glucosuria
      but did not decrease necrosis. Acivicin increased nephrotoxicity of compound A,
      and aminobenzotriazole had no consistent effect on nephrotoxicity of compound A.
      CONCLUSIONS: Nephrotoxicity of inhaled compound A in rats was associated with
      renal uptake of compound A S-conjugates and cysteine conjugates metabolism by
      renal beta-lyase. Manipulation of the beta-lyase pathway elicited similar
      results, whether compound A was administered by inhalation or intraperitoneal
      injection. Route of administration does not apparently influence nephrotoxicity
      of compound A in rats.

PMID- 9637658
TI  - Chronic desipramine treatment desensitizes the rat to anesthetic and
      antinociceptive effects of the alpha2-adrenergic agonist dexmedetomidine.
AB  - INTRODUCTION: The effects of long-term administration of the tricyclic
      antidepressant agent desipramine on the hypnotic, antinociceptive, anesthetic
      sparing, and central norepinephrine turnover suppressant action of short-term
      dexmedetomidine, a highly selective alpha2-adrenergic agonist, were studied in
      rats. METHODS: Rats were given a 3- or 4-week course of twice daily
      administration of desipramine, 10 mg/kg, or saline. The effect of a hypnotic dose
      of dexmedetomidine, 250 microg/kg given intraperitoneally, on the duration of
      loss of righting reflex was determined. The tail flick latency response was
      determined before and after 50 microg/kg dexmedetomidine. The minimum anesthetic
      concentration of halothane and the central norepinephrine turnover rate were
      determined before and after administration of 30 microg/kg dexmedetomidine.
      Changes in the affinity and density of the alpha2-adrenergic receptor in locus
      coeruleus and spinal cord also were determined. RESULTS: Treatment with
      desipramine decreased dexmedetomidine-induced loss of righting reflex duration by
      67% and eliminated the antinociceptive effect of dexmedetomidine. Dexmedetomidine
      produced a 55% decrease in minimum anesthetic concentration in the control group
      but no reduction in desipramine-treated rats. Desipramine did not change the
      receptor density or binding affinity of alpha2 receptors at the site for hypnotic
      (locus coeruleus) or antinociceptive (spinal cord) responses. No decrement in the
      central norepinephrine turnover rate was noted in the locus coeruleus of
      dexmedetomidine after 3 weeks of treatment with desipramine. The alpha1
      adrenergic antagonist prazosin at 1 or 5 mg/kg completely (minimum anesthetic
      concentration reduction), almost completely (antinociceptive), or partially
      (hypnotic) restored responsiveness to normal. CONCLUSIONS: These data indicate
      that treatment with desipramine induces hyporesponsiveness to the hypnotic,
      analgesic, and minimum anesthetic concentration-reducing, but not to the
      suppression of central norepinephrine turnover, properties of dexmedetomidine.
      The hyporesponsiveness appears to involve an alpha1-adrenergic mechanism.

PMID- 9637659
TI  - Thiopental and methohexital depress Ca2+ entry into and glutamate release from
      cultured neurons.
AB  - BACKGROUND: Although barbiturates activate alpha-aminobutyric acid type A
      receptors as part of their hypnotic effect, these drugs also inhibit voltage
      gated calcium channels. The authors determined if barbiturates could decrease
      neuronal intracellular Ca2+ transients and the resulting glutamate release.
      METHODS: Neonatal rat cerebellar granule neurons were isolated and cultured on
      coverslips and studied at 37 degrees C. Spectrofluorometric assays were used
      during identical conditions to monitor intracellular Ca2+ with the Ca2+ 
      sensitive fluorophore fura-2 and glutamate release by a glutamate dehydrogenase
      coupled assay, which produced the reduced form of nicotinamide-adenine
      dinucleotide phosphate in proportion to the amount of glutamate released. Neurons
      were depolarized by a rapid increase in external [K+] from 5 to 55 mM. Control
      responses were compared with those in the presence of 10, 30, and 100 microM
      thiopental; 3, 10, and 30 microM methohexital; decreased external [Ca2+]; or
      voltage-gated calcium channel blockers. RESULTS: Thiopental and methohexital
      depressed the intracellular Ca2+ transient peak and plateau in a dose-dependent
      manner, as did decreased Ca2+. The intermediate dose of either drug caused
      approximately 50% decrease in peak intracellular Ca2+ and 60% decrease in
      glutamate release. In the presence of specific L- and/or N-type voltage-gated
      calcium channel blockade by nicardipine or omega-conotoxin-GVIA, respectively, 30
      microM thiopental further decreased the intracellular Ca2+ transient. Thiopental
      caused a dose-dependent decrease in glutamate release, which was proportional to
      the decreased peak intracellular Ca2+. CONCLUSIONS: Thiopental and methohexital
      depress the depolarization-induced increase in intracellular Ca2+ and the
      accompanying glutamate release, actions which can contribute to the anesthetic
      and neuronal protective effects of these drugs.

PMID- 9637661
TI  - Writing successful research proposals for medical science.

PMID- 9637660
TI  - A comparative evaluation of the effects of multiple vasodilators on human
      internal mammary artery.
AB  - BACKGROUND: Vasospasm of arterial grafts represents an unpredictable complication
      of coronary artery surgery and may compromise myocardial revascularization, and
      treatment is based on empirical therapy with nitroglycerin. Because of the
      potential for tolerance to nitroglycerin to occur, the authors studied different
      vasodilators acting through separate pathways on segments of human internal
      mammary artery. METHODS: Isolated vascular rings were precontracted with
      norepinephrine (1 microM), KCl, or the thromboxane A2 analogue (U46619, 10 nm).
      Nitroglycerin (a nitrovasodilator), milrinone (a type III phosphodiesterase
      inhibitor), papaverine (a phosphodiesterase inhibitor), prostaglandin E1, and
      isradipine (a dihydropyridine calcium channel blocker) were added in a cumulative
      fashion. RESULTS: The analysis of the concentration-response curves showed that
      vasodilators induced 90-100% relaxation of the constricted segments with
      norepinephrine or the thromboxane A2 analogue, except prostaglandin E1, which
      produced 73% relaxation at maximal concentrations. The effective concentrations
      of vasodilator agent that caused 50% relaxation for nitroglycerin and milrinone
      were within the range of the reported therapeutic concentrations in plasma.
      Isradipine was also effective at reversing receptor-mediated contraction (maximal
      relaxation=100% in internal mammary artery contracted with norepinephrine;
      maximal relaxation=0% in internal mammary artery contracted with the thromboxane
      A2 analogue). CONCLUSIONS: Vasodilator drugs acting through multiple pathways are
      effective at reversing in vitro vasoconstriction.

PMID- 9637662
TI  - Malignant hyperthermia triggered coincidentally after reversal of neuromuscular
      blockade in a patient from the Hmong people of Laos.

PMID- 9637663
TI  - Nicorandil successfully abolished intraoperative torsade de pointes.

PMID- 9637664
TI  - Paraspinal fluid extravasation from long-term epidural catheter delivery system.

PMID- 9637665
TI  - Intraoperative bronchospasm induced by stimulation of the vagus nerve.

PMID- 9637666
TI  - The cuffed oropharyngeal airway, a novel adjunct to the management of difficult
      airways.

PMID- 9637667
TI  - Use of the laryngeal mask airway in laboratory cats.

PMID- 9637668
TI  - Safer endotracheal tube exchange technique.

PMID- 9637669
TI  - An alternative method for conversion of a nasal to an orotracheal intubation.

PMID- 9637670
TI  - Sympathectomy and redistribution are not the only causes of hypothermia.

PMID- 9637671
TI  - Succinylcholine duration and critical hemoglobin desaturation in the healthy
      adult.

PMID- 9637672
TI  - Safety of patient-controlled intravenous meperidine.

PMID- 9637673
TI  - PCA--not as effective but still a valuable method.

PMID- 9637674
TI  - Preinsertion pulmonary artery catheter flushing.

PMID- 9637675
TI  - A simple device to prevent back flow of blood into the intravenous line.

PMID- 9637676
TI  - LIN-12/Notch signaling: lessons from worms and flies.

PMID- 9637677
TI  - beta-cell-specific inactivation of the mouse Ipf1/Pdx1 gene results in loss of
      the beta-cell phenotype and maturity onset diabetes.
AB  - To study the late beta-cell-specific function of the homeodomain protein
      IPF1/PDX1 we have generated mice in which the Ipf1/Pdx1 gene has been disrupted
      specifically in beta cells. These mice develop diabetes with age, and we show
      that IPF1/PDX1 is required for maintaining the beta cell identity by positively
      regulating insulin and islet amyloid polypeptide expression and by repressing
      glucagon expression. We also provide evidence that IPF1/PDX1 regulates the
      expression of Glut2 in a dosage-dependent manner suggesting that lowered
      IPF1/PDX1 activity may contribute to the development of type II diabetes by
      causing impaired expression of both Glut2 and insulin.

PMID- 9637678
TI  - Myc activates telomerase.
AB  - Telomere maintenance has been proposed as an essential prerequisite to human
      tumor development. The telomerase enzyme is itself a marker for tumor cells, but
      the genetic alterations that activate the enzyme during neoplastic transformation
      have remained a mystery. Here, we show that Myc induces telomerase in both normal
      human mammary epithelial cells (HMECs) and normal human diploid fibroblasts. Myc
      increases expression of hEST2 (hTRT/TP2), the limiting subunit of telomerase, and
      both Myc and hEST2 can extend the life span of HMECs. The ability of Myc to
      activate telomerase may contribute to its ability to promote tumor formation.

PMID- 9637679
TI  - Proteasomal regulation of nuclear receptor corepressor-mediated repression.
AB  - Repression of gene transcription is a fundamental property of nuclear hormone
      receptors. We report here that cell-specific repression by nuclear receptors
      correlates with levels of nuclear receptor corepressor (N-CoR) protein. N-CoR
      protein levels are regulated by mSiah2, a mammalian homolog of Drosophila Seven
      in absentia that targets N-CoR for proteasomal degradation. mSiah2 expression is
      cell-type specific and differentially regulates the repressive activities of
      nuclear receptors. These findings establish targeted proteolysis of
      transcriptional coregulators as a mechanism for cell-specific regulation of gene
      transcription.

PMID- 9637680
TI  - Seven-up, the Drosophila homolog of the COUP-TF orphan receptors, controls cell
      proliferation in the insect kidney.
AB  - Morphogenesis of the insect kidney, the Malpighian tubules, is controlled in
      Drosophila by a single large cell, the tip cell. It has been postulated that this
      cell sends out a mitogenic signal that induces the division of neighboring cells.
      The signal and the molecules that receive it have remained elusive. We show that
      the COUP-TF-related nuclear orphan receptor Seven-up is a key component that
      becomes induced in response to mitogenic EGF receptor signaling activity
      emanating from the tip cell. Seven-up in turn is capable of regulating the
      transcription of cell cycle regulators.

PMID- 9637681
TI  - A novel protein complex that interacts with the vitamin D3 receptor in a ligand
      dependent manner and enhances VDR transactivation in a cell-free system.
AB  - Nuclear receptors transduce hormonal signals by binding directly to DNA target
      sites in promoters and modulating the transcription of linked genes. Receptor
      mediated transactivation appears to be potentiated in response to ligand by a
      number of coactivators that may provide key interactions with components of the
      transcription preinitiation complex and/or alter chromatin structure. Here, we
      use the vitamin D3 receptor ligand-binding domain (VDR LBD) as an affinity matrix
      to identify components of a transcriptionally active nuclear extract that
      interact with VDR in response to ligand. We describe the purification of a
      complex of at least 10 VDR interacting proteins (DRIPs) ranging from 65 to 250 kD
      that associate with the receptor in a strictly 1,25-dihydroxyvitamin D3-dependent
      manner. These proteins also appear to interact with other, but not all, nuclear
      receptors, such as the thyroid hormone receptor. The DRIPs are distinct from
      known nuclear receptor coactivators, although like these coactivators, their
      interaction also requires the AF-2 transactivation motif of VDR. In addition, the
      DRIP complex contains histone acetyltransferase activity, indicating that at
      least one or more of the DRIPs may function at the level of nucleosomal
      modification. However, we show that the DRIPs selectively enhance the
      transcriptional activity of VDR on a naked DNA template utilizing a cell-free,
      ligand-dependent transcription assay. Moreover, this activity can be specifically
      depleted from the extract by liganded, but not unliganded, VDR-LBD.
      Overexpression of DRIP100 in vivo resulted in a strong squelching of VDR
      transactivation, suggesting the sequestration of other limiting factors,
      including components of the DRIP complex. These results demonstrate the existence
      of a new complex of novel functional nuclear receptor coactivators.

PMID- 9637682
TI  - Kappa chain monoallelic demethylation and the establishment of allelic exclusion.
AB  - Allelic exclusion in kappa light-chain synthesis is thought to result from a
      feedback mechanism by which the expression of a functional kappa light chain on
      the surface of the B cell leads to an intracellular signal that down-regulates
      the V(D)J recombinase, thus precluding rearrangement of the other allele. Whereas
      such a feedback mechanism clearly plays a role in the maintenance of allelic
      exclusion, here we provide evidence suggesting that the initial establishment of
      allelic exclusion involves differential availability of the two kappa alleles for
      rearrangement. Analysis of kappa+ B-cell populations and of individual kappa+ B
      cells that have rearranged only one allele demonstrates that in these cells,
      critical sites on the rearranged allele are unmethylated, whereas the
      nonrearranged allele remains methylated. This pattern is apparently generated by
      demethylation that is initiated at the small pre-B cell stage, on a single
      allele, in a process that occurs prior to rearrangement and requires the presence
      in cis of both the intronic and 3' kappa enhancers. Taken together with data
      demonstrating that undermethylation is required for rearrangement, these results
      indicate that demethylation may actually underly the process of allelic exclusion
      by directing the initial choice of a single kappa allele for rearrangement.

PMID- 9637683
TI  - A stress response pathway from the endoplasmic reticulum to the nucleus requires
      a novel bifunctional protein kinase/endoribonuclease (Ire1p) in mammalian cells.
AB  - Eukaryotes respond to the presence of unfolded protein in the endoplasmic
      reticulum (ER) by up-regulating the transcription of genes encoding ER protein
      chaperones, such as BiP. We have isolated a novel human cDNA encoding a homolog
      to Saccharomyces cerevisiae Ire1p, a proximal sensor for this signal transduction
      pathway in yeast. The gene product hIre1p is a type 1 transmembrane protein
      containing a cytoplasmic domain that is highly conserved to the yeast counterpart
      having a Ser/Thr protein kinase domain and a domain homologous to RNase L.
      However, the luminal domain has extensively diverged from the yeast gene product.
      hIre1p expressed in mammalian cells displayed intrinsic autophosphorylation
      activity and an endoribonuclease activity that cleaved the 5' splice site of
      yeast HAC1 mRNA, a substrate for the endoribonuclease activity of yeast Ire1p.
      Overexpressed hIre1p was localized to the ER with particular concentration around
      the nuclear envelope and some colocalization with the nuclear pore complex.
      Expression of Ire1p mRNA was autoregulated through a process that required a
      functional hIre1p kinase activity. Finally, overexpression of wild-type hIre1p
      constitutively activated a reporter gene under transcriptional control of the rat
      BiP promoter, whereas expression of a catalytically inactive hIre1p acted in a
      trans-dominant-negative manner to prevent transcriptional activation of the BiP
      promoter in response to ER stress induced by inhibition of N-linked
      glycosylation. These results demonstrate that hIre1p is an essential proximal
      sensor of the unfolded protein response pathway in mammalian cells.

PMID- 9637684
TI  - The ErbB2 and ErbB3 receptors and their ligand, neuregulin-1, are essential for
      development of the sympathetic nervous system.
AB  - Neuregulins (NDF, heregulin, GGF ARIA, or SMDF) are EGF-like growth and
      differentiation factors that signal through tyrosine kinase receptors of the ErbB
      family. Here, we report a novel phenotype in mice with targeted mutations in the
      erbB2, erbB3, or neuregulin-1 genes. These three mutations cause a severe
      hypoplasia of the primary sympathetic ganglion chain. We provide evidence that
      migration of neural crest cells to the mesenchyme lateral of the dorsal aorta, in
      which they differentiate into sympathetic neurons, depends on neuregulin-1 and
      its receptors. Neuregulin-1 is expressed at the origin of neural crest cells.
      Moreover, a tight link between neuregulin-1 expression, the migratory path, and
      the target site of sympathogenic neural crest cells is observed. Sympathetic
      ganglia synthesize catecholamines in the embryo and the adult. Accordingly,
      catecholamine levels in mutant embryos are severely decreased, and we suggest
      that the lack of catecholamines contributes to the embryonal lethality of the
      erbB3 mutant mice. Thus, neuregulin-1, erbB2, and erbB3 are required for the
      formation of the sympathetic nervous system; the block in development observed in
      mutant mice is caused by a lack of neural crest precursor cells in the anlage of
      the primary sympathetic ganglion chain. Together with previous observations,
      these findings establish the neuregulin signaling system as a key regulator in
      the development of neural crest cells.

PMID- 9637685
TI  - Miranda as a multidomain adapter linking apically localized Inscuteable and
      basally localized Staufen and Prospero during asymmetric cell division in
      Drosophila.
AB  - Neuroblasts in the developing Drosophila CNS asymmetrically localize the cell
      fate determinants Numb and Prospero as well as prospero RNA to the basal cortex
      during mitosis. The localization of Prospero requires the function of inscuteable
      and miranda, whereas prospero RNA localization requires inscuteable and staufen
      function. We demonstrate that Miranda contains multiple functional domains: an
      amino-terminal asymmetric localization domain, which interacts with Inscuteable,
      a central Numb interaction domain, and a more carboxy-terminal Prospero
      interaction domain. We also show that Miranda and Staufen have similar
      subcellular localization patterns and interact in vitro. Furthermore, miranda
      function is required for the asymmetric localization of Staufen. Miranda
      localization is disrupted by the microfilament disrupting agent latrunculin A.
      Our results suggest that Miranda directs the basal cortical localization of
      multiple molecules, including Staufen and prospero RNA, in mitotic neuroblasts in
      an actin-dependent manner.

PMID- 9637686
TI  - Miranda mediates asymmetric protein and RNA localization in the developing
      nervous system.
AB  - Neuroblasts undergo asymmetric stem cell divisions to generate a series of
      ganglion mother cells (GMCs). During these divisions, the cell fate determinant
      Prospero is asymmetrically partitioned to the GMC by Miranda protein, which
      tethers it to the basal cortex of the dividing neuroblast. Interestingly,
      prospero mRNA is similarly segregated by the dsRNA binding protein, Staufen. Here
      we show that Staufen interacts in vivo with a segment of the prospero 3' UTR.
      Staufen protein and prospero RNA colocalize to the apical side of the neuroblast
      at interphase, but move to the basal side during prophase. Both the apical and
      basal localization of Staufen are abolished by the removal of a conserved domain
      from the carboxyl terminus of the protein, which interacts in a yeast two-hybrid
      screen with Miranda protein. Furthermore, Miranda colocalizes with Staufen
      protein and prospero mRNA during neuroblast divisions, and neither Staufen nor
      prospero RNA are localized in miranda mutants. Thus Miranda, which localizes
      Prospero protein, also localizes prospero RNA through its interaction with
      Staufen protein.

PMID- 9637687
TI  - Binary sibling neuronal cell fate decisions in the Drosophila embryonic central
      nervous system are nonstochastic and require inscuteable-mediated asymmetry of
      ganglion mother cells.
AB  - Asymmetric cell division is a widespread mechanism in developing tissues that
      leads to the generation of cell diversity. In the embryonic central nervous
      system of Drosophila melanogaster, secondary precursor cells-ganglion mother
      cells (GMCs)-divide and produce postmitotic neurons that take on different cell
      fates. In this study, we show that binary fate decision of two pairs of sibling
      neurons is accomplished through the interplay of Notch (N) signaling and the
      intrinsic fate determinant Numb. We show that GMCs have apical-basal polarity and
      Numb localization and the orientation of division are coordinated to segregate
      Numb to only one sibling cell. The correct positioning of Numb and the proper
      orientation of division require Inscuteable (Insc). Loss of insc results in the
      generation of equivalent sibling cells. Our results provide evidence that sibling
      neuron fate decision is nonstochastic and normally depends on the presence of
      Numb in one of the two siblings. Moreover, our data suggest that the fate of some
      sibling neurons may be regulated by signals that do not require lateral
      interaction between the sibling cells.

PMID- 9637688
TI  - The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary
      complex with the anaphase-promoting complex to control anaphase initiation.
AB  - The spindle assembly checkpoint mechanism delays anaphase initiation until all
      chromosomes are aligned at the metaphase plate. Activation of the anaphase
      promoting complex (APC) by binding of CDC20 and CDH1 is required for exit from
      mitosis, and APC has been implicated as a target for the checkpoint intervention.
      We show that the human checkpoint protein hMAD2 prevents activation of APC by
      forming a hMAD2-CDC20-APC complex. When injected into Xenopus embryos, hMAD2
      arrests cells at mitosis with an inactive APC. The recombinant hMAD2 protein
      exists in two-folded states: a tetramer and a monomer. Both the tetramer and the
      monomer bind to CDC20, but only the tetramer inhibits activation of APC and
      blocks cell cycle progression. Thus, hMAD2 binding is not sufficient for
      inhibition, and a change in hMAD2 structure may play a role in transducing the
      checkpoint signal. There are at least three different forms of mitotic APC that
      can be detected in vivo: an inactive hMAD2-CDC20-APC ternary complex present at
      metaphase, a CDC20-APC binary complex active in degrading specific substrates at
      anaphase, and a CDH1-APC complex active later in mitosis and in G1. We conclude
      that the checkpoint-mediated cell cycle arrest involves hMAD2 receiving an
      upstream signal to inhibit activation of APC.

PMID- 9637689
TI  - A bacterial ATP-dependent, enhancer binding protein that activates the
      housekeeping RNA polymerase.
AB  - A commonly accepted view of gene regulation in bacteria that has emerged over the
      last decade is that promoters are transcriptionally activated by one of two
      general mechanisms. The major type involves activator proteins that bind to DNA
      adjacent to where the RNA polymerase (RNAP) holoenzyme binds, usually assisting
      in recruitment of the RNAP to the promoter. This holoenzyme uses the housekeeping
      sigma70 or a related factor, which directs the core RNAP to the promoter and
      assists in melting the DNA near the RNA start site. A second type of mechanism
      involves the alternative sigma factor (called sigma54 or sigmaN) that directs
      RNAP to highly conserved promoters. In these cases, an activator protein with an
      ATPase function oligomerizes at tandem sites far upstream from the promoter. The
      nitrogen regulatory protein (NtrC) from enteric bacteria has been the model for
      this family of activators. Activation of the RNAP/sigma54 holoenzyme to form the
      open complex is mediated by the activator, which is tethered upstream. Hence,
      this class of protein is sometimes called the enhancer binding protein family or
      the NtrC class. We describe here a third system that has properties of each of
      these two types. The NtrC enhancer binding protein from the photosynthetic
      bacterium, Rhodobacter capsulatus, is shown in vitro to activate the housekeeping
      RNAP/sigma70 holoenzyme. Transcriptional activation by this NtrC requires ATP
      binding but not hydrolysis. Oligomerization at distant tandem binding sites on a
      supercoiled template is also necessary. Mechanistic and evolutionary questions of
      these systems are discussed.

PMID- 9637690
TI  - Renal agenesis in mice homozygous for a gene trap mutation in the gene encoding
      heparan sulfate 2-sulfotransferase.
AB  - Heparan sulfate proteoglycans have been implicated in the presentation of a
      number of secreted signaling molecules to their signal-transducing receptors. We
      have characterized a gene trap mutation in the gene encoding a heparan sulfate
      biosynthetic enzyme, heparan sulfate 2-sulfotransferase (HS2ST). Transgenic mice
      were generated from embryonic stem cells harboring this insertion. lacZ reporter
      gene activity in heterozygous embryos demonstrates that the gene is expressed
      differentially during embryogenesis, presumably directing dynamic changes in
      heparan sulfate structure. Moreover, mice homozygous for the Hs2st gene trap
      allele die in the neonatal period, exhibiting bilateral renal agenesis and
      defects of the eye and the skeleton. Analysis of kidney development in Hs2st
      mutants reveals that the gene is not required for two early events-ureteric bud
      outgrowth from the Wolffian duct and initial induction of Pax-2 expression in the
      metanephric mesenchyme. It is required, however, for mesenchymal condensation
      around the ureteric bud and initiation of branching morphogenesis. Because 2-O
      sulfation has been shown to influence the functional interactions of ligands with
      heparan sulfate in vitro, we discuss the possibility that the Hs2st mutant
      phenotype is a consequence of compromised interactions between growth factors and
      their signal-transducing receptors. These data provide the first genetic evidence
      that the regulated synthesis of differentially glycosylated proteoglycans can
      affect morphogenesis during vertebrate development.

PMID- 9637691
TI  - The C/EBPbeta transcription factor regulates epithelial cell proliferation and
      differentiation in the mammary gland.
AB  - Studies of C/EBPbeta-deficient mice have demonstrated a pivotal role for this
      transcription factor in hematopoiesis, adipogenesis, and ovarian function. Here
      we show that C/EBPbeta is also essential for normal development and function of
      the mammary gland. Ductal morphogenesis in virgin C/EBPbeta-deficient mice was
      disrupted, with ducts displaying reduced growth and branching. To distinguish
      whether the effect of C/EBPbeta deficiency on mammary epithelium is indirect or
      cell autonomous, we performed ovarian and mammary gland transplants. Transplants
      of wild-type ovaries into mutant females partially restored ductal morphogenesis
      during puberty but failed to support mammopoiesis during pregnancy. At term,
      mutant mice harboring wild-type ovaries exhibited reduced alveolar proliferation
      and impaired epithelial cell differentiation, including a complete absence of
      milk protein expression. Mammary gland transplant experiments demonstrated that
      development of C/EBPbeta-deficient epithelium was defective within a wild-type
      stroma and host background. Cell proliferation during pregnancy was reduced and
      differentiation, as measured by the activity of milk protein genes, was
      inhibited. However, wild-type epithelium developed in a C/EBPbeta-deficient
      stroma. Thus, C/EBPbeta plays an essential, cell autonomous role in the
      proliferation and differentiation of mammary secretory epithelial cells and is
      required for the activation of milk protein genes.

PMID- 9637693
TI  - An ongoing debate over phenylalanine hydroxylase deficiency in phenylketonuria.

PMID- 9637692
TI  - C/EBPbeta, but not C/EBPalpha, is essential for ductal morphogenesis,
      lobuloalveolar proliferation, and functional differentiation in the mouse mammary
      gland.
AB  - The CCAAT/enhancer binding proteins (C/EBPs) are differentially expressed
      throughout mammary gland development and interact with binding sites within the
      promoter of a milk protein gene, beta-casein. The specific roles of C/EBPbeta and
      C/EBPalpha in mouse mammary gland development and differentiation have been
      investigated in mice that carry targeted deletions of these genes. C/EBPbeta-/-
      virgin mice exhibited cystic, enlarged mammary ducts with decreased secondary
      branching. Transplantation of C/EBPbeta-/- mammary epithelium into the cleared
      mammary fat pads of nude mice confirmed that this defect in ductal morphogenesis
      was intrinsic to the epithelium. When treated with estrogen/progesterone (E+P) to
      simulate pregnancy, C/EBPbeta-/- mammary glands displayed only limited
      lobuloalveolar development and ductal side branching. Primary mammary epithelial
      cells obtained from E+P-treated C/EBPbeta-/- mice that were cultured on
      extracellular matrix gels did not functionally differentiate in response to
      lactogenic hormones despite their organization into three-dimensional structures.
      Expression of beta-casein protein was inhibited 85%-100% and whey acidic protein
      (WAP) was undetectable. In contrast, no detectable alterations in mammary
      development or beta-casein expression were observed in mammary outgrowths derived
      from newborn C/EBPalpha-/- mammary epithelium transplanted into the cleared
      mammary fat pads of syngeneic hosts. These results demonstrate that C/EBPbeta,
      but not C/EBPalpha, is required for ductal morphogenesis, lobuloalveolar
      development, and functional differentiation of mammary epithelial cells.

PMID- 9637694
TI  - Plasmid DNA encoding transforming growth factor-beta1 suppresses chronic disease
      in a streptococcal cell wall-induced arthritis model.
AB  - Transforming growth factor beta is a potent immunomodulator with both pro- and
      antiinflammatory activities. Based on its immunosuppressive actions, exogenous
      TGF-beta has been shown to inhibit autoimmune and chronic inflammatory diseases.
      To further explore the potential therapeutic role of TGF-beta, we administered a
      plasmid DNA encoding human TGF-beta1 intramuscularly to rats with streptococcal
      cell wall-induced arthritis. A single dose of 300 microg plasmid DNA encoding TGF
      beta1, but not vector DNA, administered at the peak of the acute phase profoundly
      suppressed the subsequent evolution of chronic erosive disease typified by
      disabling joint swelling and deformity (articular index = 8.17+/-0. 17 vs. 1.25+/
      0.76, n = 6, day 26, P < 0.01). Moreover, delivery of the TGF-beta1 DNA even as
      the chronic phase commenced virtually eliminated subsequent inflammation and
      arthritis. Both radiologic and histopathologic as well as molecular evidence
      supported the marked inhibitory effect of TGF-beta1 DNA on synovial pathology,
      with decreases in the inflammatory cell infiltration, pannus formation, cartilage
      and bone destruction, and the expression of proinflammatory cytokines that
      characterize this model. Increases in TGF-beta1 protein were detected in the
      circulation of TGF-beta1 DNA-treated animals, consistent with the observed
      therapeutic effects being TGF-beta1 dependent. These observations provide the
      first evidence that gene transfer of plasmid DNA encoding TGF-beta1 provides a
      mechanism to deliver this potent cytokine that effectively suppresses ongoing
      inflammatory pathology in arthritis.

PMID- 9637695
TI  - Androgens stimulate early stages of follicular growth in the primate ovary.
AB  - The concept that androgens are atretogenic, derived from murine ovary studies, is
      difficult to reconcile with the fact that hyperandrogenic women have more
      developing follicles than normal-cycling women. To evaluate androgen's effects on
      primate follicular growth and survival, normal-cycling rhesus monkeys were
      treated with placebo-, testosterone-(T), or dihydrotestosterone-sustained release
      implants, and ovaries were taken for histological analysis after 3-10 d of
      treatment. Growing preantral and small antral follicles up to 1 mm in diameter
      were significantly and progressively increased in number and thecal layer
      thickness in T-treated monkeys from 3-10 d. Granulosa and thecal cell
      proliferation, as determined by immunodetection of the Ki67 antigen, were
      significantly increased in these follicles. Preovulatory follicles (> 1 mm),
      however, were not increased in number in androgen-treated animals. Follicular
      atresia was not increased and there were actually significantly fewer apoptotic
      granulosa cells in the T-treated groups. Dihydrotestosterone treatment had
      identical effects, indicating that these growth-promoting actions are mediated by
      the androgen receptor. These findings show that, over the short term at least,
      androgens are not atretogenic and actually enhance follicular growth and survival
      in the primate. These new data provide a plausible explanation for the
      pathogenesis of "polycystic" ovaries in hyperandrogenism.

PMID- 9637696
TI  - Functional significance of cardiac myosin essential light chain isoform switching
      in transgenic mice.
AB  - The different functions of the ventricular- and atrial-specific essential myosin
      light chains are unknown. Using transgenesis, cardiac-specific overexpression of
      proteins can be accomplished. The transgenic paradigm is more useful than
      originally expected, in that the mammalian heart rigorously controls sarcomeric
      protein stoichiometries. In a clinical subpopulation suffering from heart disease
      caused by congenital malformations of the outflow tract, an ELC1v-->ELC1a isoform
      shift correlated with increases in cross-bridge cycling kinetics as measured in
      skinned fibers derived from the diseased muscle. We have used transgenesis to
      replace the ventricular isoform of the essential myosin light chain with the
      atrial isoform. The ELC1v--> ELC1a shift in the ventricle resulted in similar
      functional alterations. Unloaded velocities as measured by the ability of the
      myosin to translocate actin filaments in the in vitro motility assay were
      significantly increased as a result of the isoform substitution. Unloaded
      shortening velocity was also increased in skinned muscle fibers, and at the whole
      organ level, both contractility and relaxation were significantly increased. This
      increase in cardiac function occurred in the absence of a hypertrophic response.
      Thus, ELC1a expression in the ventricle appears to be advantageous to the heart,
      resulting in increased cardiac function.

PMID- 9637697
TI  - Vaccination with a recombinant fragment of collagen adhesin provides protection
      against Staphylococcus aureus-mediated septic death.
AB  - Staphylococcus aureus is a major cause of nosocomial and community-acquired
      infections. Morbidity and mortality due to infections such as sepsis,
      osteomyelitis, septic arthritis, and invasive endocarditis remain high despite
      the use of antibiotics. The emergence of antibiotic resistant super bugs mandates
      that alternative strategies for the prevention and treatment of S. aureus
      infections are developed. We investigated the ability of vaccination with a
      recombinant fragment of the S. aureus collagen adhesin to protect mice against
      sepsis-induced death. Actively immunized NMRI mice were intravenously inoculated
      with the S. aureus clinical isolate strain Phillips. 14 d after inoculation,
      mortality in the collagen adhesin-vaccinated group was only 13%, compared with
      87% in the control antigen immunized group (P < 0.001). To determine if the
      protective effect was antibody mediated, we passively immunized naive mice with
      collagen adhesin-specific antibodies. Similar to the active immunization
      strategy, passive transfer of collagen adhesin-specific antibodies protected mice
      against sepsis-induced death. In vitro experiments indicated that S. aureus
      opsonized with sera from collagen adhesin immunized mice promoted phagocytic
      uptake and enhanced intracellular killing compared with bacteria opsonized with
      sera from control animals. These results indicate that the collagen adhesin is a
      viable target in the development of immunotherapeutics against S. aureus.

PMID- 9637698
TI  - Regulation of proliferation of human colonic subepithelial myofibroblasts by
      mediators important in intestinal inflammation.
AB  - An increase in myofibroblast number may be necessary for wound healing but may
      also lead to postinflammatory scarring. We have, therefore, studied the role of
      mediators important in inflammatory bowel disease in regulating proliferation of
      human colonic myofibroblasts. Using primary cultures of these cells, we have
      shown increases in [3H]thymidine incorporation in response to platelet-derived
      growth factor (EC50 = 14 ng/ml), basic fibroblast growth factor (EC50 = 2.2
      ng/ml), and epidermal growth factor (EC50 = 1.1 ng/ml). Coulter counting of cell
      suspensions demonstrated increases in cell number with these growth factors along
      with insulin-like growth factor-I and -II. In addition the proinflammatory
      cytokines IL-1beta and TNF-alpha produced increases in [3H]thymidine
      incorporation. IL-1beta and platelet-derived growth factor together produced an
      increase in [3H]thymidine greater than either agonist alone; this effect was not,
      however, seen when we examined changes in cell numbers. Finally, we demonstrate a
      mechanism whereby these responses may be downregulated: vasoactive intestinal
      peptide (1 microM) elevates cyclic AwMP in these cells 4. 2-fold over control and
      produces a dose-related inhibition of platelet-derived growth factor-driven
      proliferation with a maximum inhibition of 33% at 1 microM.

PMID- 9637699
TI  - Identification of the principal proteoglycan-binding site in LDL. A single-point
      mutation in apo-B100 severely affects proteoglycan interaction without affecting
      LDL receptor binding.
AB  - The subendothelial retention of LDLs through their interaction with proteoglycans
      has been proposed to be a key process in the pathogenesis of atherosclerosis. In
      vitro studies have identified eight clusters of basic amino acids in delipidated
      apo-B100, the protein moiety of LDL, that bind the negatively charged
      proteoglycans. To determine which of these sites is functional on the surface of
      LDL particles, we analyzed the proteoglycan-binding activity of recombinant human
      LDL isolated from transgenic mice. Substitution of neutral amino acids for the
      basic amino acids residues in site B (residues 3359-3369) abolished both the
      receptor-binding and the proteoglycan-binding activities of the recombinant LDL.
      Chemical modification of the remaining basic residues caused only a marginal
      further reduction in proteoglycan binding, indicating that site B is the primary
      proteoglycan-binding site of LDL. Although site B was essential for normal
      receptor-binding and proteoglycan-binding activities, these activities could be
      separated in recombinant LDL containing single-point mutation. Recombinant LDL
      with a K3363E mutation, in which a glutamic acid had been inserted into the basic
      cluster RKR in site B, had normal receptor binding but interacted defectively
      with proteoglycans; in contrast, another mutant LDL, R3500Q, displayed defective
      receptor binding but interacted normally with proteoglycans. LDL with normal
      receptor-binding activity but with severely impaired proteoglycan binding will be
      a unique resource for analyzing the importance of LDL- proteoglycan interaction
      in atherogenesis. If the subendothelial retention of LDL by proteoglycans is the
      initial event in early atherosclerosis, then LDL with defective proteoglycan
      binding may have little or no atherogenic potential.

PMID- 9637700
TI  - Stimulation of bile duct epithelial secretion by glybenclamide in normal and
      cholestatic rat liver.
AB  - Cholestasis is a cardinal complication of liver disease, but most treatments are
      merely supportive. Here we report that the sulfonylurea glybenclamide potently
      stimulates bile flow and bicarbonate excretion in the isolated perfused rat
      liver. Video-microscopic studies of isolated hepatocyte couplets and isolated
      bile duct segments show that this stimulatory effect occurs at the level of the
      bile duct epithelium, rather than through hepatocytes. Measurements of cAMP,
      cytosolic pH, and Ca2+ in isolated bile duct cells suggest that glybenclamide
      directly activates Na+-K+-2Cl- cotransport, rather than other transporters or
      conventional second-messenger systems that link to secretory pathways in these
      cells. Finally, studies in livers from rats with endotoxin- or estrogen-induced
      cholestasis show that glybenclamide retains its stimulatory effects on bile flow
      and bicarbonate excretion even under these conditions. These findings suggest
      that bile duct epithelia may represent an important new therapeutic target for
      treatment of cholestatic disorders.

PMID- 9637701
TI  - Gender differences in ethanol preference and ingestion in rats. The role of the
      gonadal steroid environment.
AB  - An ethanol oral self administration paradigm showed the existence of gender
      differences in alcohol preference in rats: whereas males and females initiated
      alcohol drinking at similar rates, females maintained their preference for
      ethanol over a longer duration. Neonatal estrogenization of females, which
      effectively confers a male phenotype on a genetically female brain, resulted in
      patterns of drinking that were similar to those displayed by intact male rats,
      indicating that gender differences in alcohol drinking patterns may be, at least
      partially, accounted for by sexual differentiation of the brain. To test whether
      gonadal steroids also exert activational effects on ethanol-seeking behavior, we
      also examined the effects of gonadectomy alone, or in combination with gonadal
      steroid replacement therapy. Castration did not significantly alter ethanol
      consumption in males, although treatment of castrated rats with
      dihydrotestosterone resulted in a significant inhibition of this parameter. As
      compared with the situation in intact female rats, ethanol ingestion was
      significantly reduced in ovariectomized female rats receiving estradiol (E2) and
      in ovariectomized female rats receiving combined E2 and progesterone replacement
      therapy. However, neither ovariectomy nor progesterone replacement in
      ovariectomized rats resulted in ethanol drinking patterns that were different
      compared to those observed in intact female controls. Thus, dihydrotestosterone
      and E2, respectively, appear to exert modulatory influences on the male and
      female rats' preference for ethanol, but further investigations are necessary to
      determine to what extent these effects result from activational actions on the
      brain.

PMID- 9637702
TI  - In vitro generation of human cytomegalovirus pp65 antigenemia, viremia, and
      leukoDNAemia.
AB  - Immunocompromised patients with disseminated human cytomegalovirus (HCMV)
      infection have circulating PMN carrying HCMV pp65 (antigenemia), infectious virus
      (viremia), and viral DNA (leukoDNAemia). Because HCMV does not fully replicate in
      PMN, it is generally hypothesized that virions and viral materials are taken up
      by phagocytosis from fully permissive HCMV-infected endothelial cells. However,
      no experimental evidence has ever been provided for these PMN-endothelium
      interactions. PMN from 11 donors were cocultured with endothelial cells infected
      with an endothelium-adapted HCMV strain and with human fibroblasts infected with
      low-passaged clinical and laboratory-adapted HCMV strains. pp65-positive PMN were
      detected after coculture with both HCMV-infected endothelial and fibroblast
      cells, provided that wild and not laboratory-adapted strains were used. In
      addition, cocultured PMN carried infectious virus as demonstrated by virus
      isolation and presence of complete virus particles by electron microscopy.
      Moreover, high levels of viral DNA were consistently detected by quantitative PCR
      in cocultured PMN. Thus, we have generated in vitro the three most important
      viral parameters detected in patients with disseminated HCMV infection
      (antigenemia, viremia, and leukoDNAemia). The failure of laboratory-adapted HCMV
      strain to induce this phenomenon demonstrates that important modifications have
      occurred in attenuated viral strains affecting basic biological functions.

PMID- 9637703
TI  - Inhibition of intracellular degradation increases secretion of a mutant form of
      alpha1-antitrypsin associated with profound deficiency.
AB  - The mutant Z form of alpha1-antitrypsin (alpha1AT) is responsible for > 95% of
      all individuals with alpha1AT deficiency, an important inherited cause of
      emphysema and liver disease. Since secreted Z alpha1AT is a functional
      antiprotease, we hypothesized that interrupting catabolism of retained Z alpha1AT
      might increase its transport out of cells, causing an increase in extracellular
      protease protection. Both the protein translation inhibitor cycloheximide and the
      specific inhibitor of proteasome function, lactacystin, prevented intracellular
      degradation of Z alpha1AT. Moreover, this inhibition of degradation was
      associated with partial restoration of Z alpha1AT vesicular transport. This
      effect was observed in a model system of transfected CHO cells as well as in
      human alveolar macrophages synthesizing Z alpha1AT. This study supports the
      hypothesis that altering the intracellular fate of a mutant protein may be an
      option in the treatment of diseases associated with misfolded but potentially
      functional proteins.

PMID- 9637704
TI  - Heterozygous osteopetrotic (op) mutation reduces atherosclerosis in LDL receptor-
      deficient mice.
AB  - Previous studies of osteopetrotic (op) mice lacking macrophage colony-stimulating
      factor (M-CSF) have revealed an inhibition of atherosclerosis development in the
      apolipoprotein E (apo E)-deficient model and in a diet-induced model. Using LDL
      receptor-deficient mice, we now show that atheroma development depends on M-CSF
      concentration, as not only did homozygous osteopetrotic (op/op) mice have
      dramatically reduced lesions (approximately 0.3% of control lesion size) but
      heterozygous (op/+) mice had lesions < 1% of controls. Mice heterozygous for the
      op mutation (op/+) had plasma levels of M-CSF about half those in controls (+/+).
      The finding that an approximately 2-fold reduction in M-CSF expression reduced
      lesion size approximately 100-fold suggests the requirement for a threshold level
      of M-CSF. The effect of M-CSF on atherosclerosis did not appear to be mediated
      either by changes in plasma lipoprotein levels or alterations in the number of
      circulating monocytes, since both op/op and op/+ mice exhibited higher levels of
      atherogenic lipoprotein particles and (op/+) mice showed a near normal number of
      circulating monocytes. LDL receptor-null littermates of genotypes from op/op,
      op/+, to +/+ showed monocyte differentials of approximately 4.5, 8, and 10%,
      respectively. Taken together, these results suggest that the effects of M-CSF on
      atherogenesis may not be mediated by expression of M-CSF systemically or by
      modulation of the number of circulating monocytes. These studies support the
      conclusion that M-CSF participates critically in fatty streak formation and
      progression to a complex fibrous lesion.

PMID- 9637705
TI  - Effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, atorvastatin
      and simvastatin, on the expression of endothelin-1 and endothelial nitric oxide
      synthase in vascular endothelial cells.
AB  - Endothelial dysfunction associated with atherosclerosis has been attributed to
      alterations in the L-arginine-nitric oxide (NO)-cGMP pathway or to an excess of
      endothelin-1 (ET-1). The 3-hydroxy-3-methylglutaryl coenzyme A reductase
      inhibitors (statins) have been shown to ameliorate endothelial function. However,
      the physiological basis of this observation is largely unknown. We investigated
      the effects of Atorvastatin and Simvastatin on the pre-proET-1 mRNA expression
      and ET-1 synthesis and on the endothelial NO synthase (eNOS) transcript and
      protein levels in bovine aortic endothelial cells. These agents inhibited pre
      proET-1 mRNA expression in a concentration- and time-dependent fashion (60-70%
      maximum inhibition) and reduced immunoreactive ET-1 levels (25-50%). This
      inhibitory effect was maintained in the presence of oxidized LDL (1-50
      microg/ml). No significant modification of pre-proET-1 mRNA half-life was
      observed. In addition, mevalonate, but not cholesterol, reversed the statin
      mediated decrease of pre-proET-1 mRNA levels. eNOS mRNA expression was reduced by
      oxidized LDL in a dose-dependent fashion (up to 57% inhibition), whereas native
      LDL had no effect. Statins were able to prevent the inhibitory action exerted by
      oxidized LDL on eNOS mRNA and protein levels. Hence, these drugs might influence
      vascular tone by modulating the expression of endothelial vasoactive factors.

PMID- 9637706
TI  - beta2-Microglobulin mutations, HLA class I antigen loss, and tumor progression in
      melanoma.
AB  - The potential negative impact of HLA class I antigen abnormalities on the outcome
      of T cell-based immunotherapy of melanoma has prompted us to investigate the
      mechanisms underlying lack of HLA class I antigen expression by melanoma cell
      lines Me18105, Me9923, and Me1386. Distinct mutations in the beta2-microglobulin
      (beta2m) gene were identified in each cell line which result in loss of
      functional beta2m. In Me18105 cells, an aberrant splicing mechanism caused by an
      A--> G point mutation in the splice acceptor site of intron 1 of the beta2m gene,
      deletes 11 bp from the beta2m mRNA creating a shift in the reading frame. In
      Me9923 cells a 14-bp deletion in exon 2 and in Me1386 cells a CT deletion in exon
      1 of the beta2m gene produce a frameshift mutation. The beta2m gene mutations
      identified in Me18105, Me9923, and Me1386 cells were also detected in the
      surgically removed melanoma lesions from which the cell lines originated.
      Transfection of each melanoma cell line with a wild-type beta2m gene restored HLA
      class I antigen expression and, in Me18105 cells, recognition by Melan-A/MART-1
      specific, HLA-A2-restricted cytotoxic T lymphocytes. Interestingly, the beta2m
      mutation present in Me9923 cells that were derived from a metastatic lesion was
      also found in the Me9923P cell line that originated from the autologous primary
      lesion. These data suggest that beta2m mutations in melanoma cells may be an
      early event in progression to the malignant phenotype.

PMID- 9637707
TI  - Time-dependent changes in the density and hemoglobin F content of biotin-labeled
      sickle cells.
AB  - Sickle red blood cells (RBC) are subject to a number of important cellular
      changes and selection pressures. In this study, we validated a biotin RBC label
      by comparison to the standard 51Cr label, and used it to study changes that occur
      in sickle cells as they age. Sickle RBC had a much shorter lifespan than normal
      RBC, but the two labels gave equivalent results for each cell type. A variable
      number of sickle, but not normal, RBC disappeared from the circulation during the
      first few hours after reinfusion. The number of biotinylated sickle reticulocytes
      was decreased by 50% after 24 h and 75% after 48 h, with a gradual decrease in
      the amount of reticulum per cell. The labeled sickle cells exhibited major
      density increases during the first 4-6 d after reinfusion, with smaller changes
      thereafter. A small population of very light, labeled sickle RBC was essentially
      constant in number after the first few days. Fetal hemoglobin (HbF) content was
      determined in isolated biotinylated sickle RBC after reinfusion, allowing an
      estimate of lifespan for RBC containing HbF (F cells) and non-F cells. The
      lifespan of sickle biotinylated RBC lacking HbF was estimated to be approximately
      2 wk, whereas F cells survived 6-8 wk.

PMID- 9637708
TI  - Mutations causing Liddle syndrome reduce sodium-dependent downregulation of the
      epithelial sodium channel in the Xenopus oocyte expression system.
AB  - Liddle syndrome is an autosomal dominant form of hypertension resulting from
      deletion or missense mutations of a PPPxY motif in the cytoplasmic COOH terminus
      of either the beta or gamma subunit of the epithelial Na channel (ENaC). These
      mutations lead to increased channel activity. In this study we show that wild
      type ENaC is downregulated by intracellular Na+, and that Liddle mutants decrease
      the channel sensitivity to inhibition by intracellular Na+. This event results at
      high intracellular Na+ activity in 1.2-2.4-fold higher cell surface expression,
      and 2.8-3.5-fold higher average current per channel in Liddle mutants compared
      with the wild type. In addition, we show that a rapid increase in the
      intracellular Na+ activity induced downregulation of the activity of wild-type
      ENaC, but not Liddle mutants, on a time scale of minutes, which was directly
      correlated to the magnitude of the Na+ influx into the oocytes. Feedback
      inhibition of ENaC by intracellular Na+ likely represents an important cellular
      mechanism for controlling Na+ reabsorption in the distal nephron that has
      important implications for the pathogenesis of hypertension.

PMID- 9637709
TI  - Association and direct activation of signal transducer and activator of
      transcription1alpha by platelet-derived growth factor receptor.
AB  - PDGF stimulates tyrosine phosphorylation of Janus kinase 1 (JAK1) and the signal
      transducer and activator of transcription 1 (STAT1alpha). However, it is not
      known whether JAKs are required for STAT1alpha phosphorylation or if the PDGF
      receptor itself can directly tyrosine phosphorylate and activate STAT1alpha. In
      vitro immunecomplex kinase assay of PDGF beta receptor (PDGFR) or STAT1alpha
      immunoprecipitates from lysates of mesangial cells treated with PDGF showed
      phosphorylation of a 91- and an 185-kD protein. Incubation of lysates prepared
      from quiescent mesangial cells with purified PDGFR resulted in STAT1alpha
      activation. Immunodepletion of Janus kinases from the cell lysate before
      incubation with the purified PDGFR showed no effect on STAT1alpha activation.
      Moreover, lysates from mesangial cells treated with JAK2 inhibitor, retained
      significant STAT1alpha activity. To confirm that STAT1alpha is a substrate for
      PDGFR, STAT1alpha protein was prepared by in vitro transcription and translation.
      The addition of purified PDGFR to the translated STAT1alpha resulted in its
      phosphorylation. This in vitro phosphorylated and activated protein also forms a
      specific protein-DNA complex. Dimerization of the translated STAT1alpha protein
      was also required for its DNA binding. Incubation of pure STAT1alpha with
      autophosphorylated PDGFR resulted in physical association of the two proteins.
      These data indicate that activated PDGFR may be sufficient to tyrosine
      phosphorylate and thus directly activate STAT1alpha.

PMID- 9637710
TI  - Delta-aminolevulinic acid transport by intestinal and renal peptide transporters
      and its physiological and clinical implications.
AB  - Delta-aminolevulinic acid (ALA) is the precursor of porphyrin synthesis and has
      been recently used in vitro and in clinical studies as an endogenous
      photosensitizer for photodynamic therapy in the treatment of various tumors. For
      this purpose, ALA is given topically, systemically, or orally. When administered
      by the oral route, it shows excellent intestinal absorption. ALA is also
      efficiently reabsorbed in the renal proximal tubule after glomerular filtration.
      However, the pathways and mechanisms for its transmembrane transport into
      epithelial cells of intestine and kidney are unknown. Here we demonstrate that
      ALA uses the intestinal and renal apical peptide transporters for entering into
      epithelial cells. Kinetics and characteristics of ALA transport were determined
      in Xenopus laevis ooyctes and Pichia pastoris yeast cells expressing either the
      cloned intestinal peptide transporter PEPT1 or the renal form PEPT2. By using
      radiolabeled ALA and electrophysiological techniques in these heterologous
      expression systems, we established that: (a) PEPT1 and PEPT2 translocate 3H-ALA
      by saturable and pH-dependent transport mechanisms, (b) that ALA and di
      /tripeptides, but not GABA or related amino acids, compete at the same substrate
      binding site of the carriers, and (c) that ALA transport is electrogenic in
      nature as a consequence of H+/ALA cotransport. Reverse transcriptase-PCR analysis
      performed with specific primers for PEPT1 and PEPT2 in rabbit tissues
      demonstrates that, in particular, the PEPT2 mRNA is expressed in a variety of
      other tissues including lung, brain, and mammary gland, which have been shown to
      accumulate ALA. This suggests that these tissues could take up the porphyrin
      precusor via expressed peptide transporters, providing the endogenous
      photosensitizers for efficient photodynamic therapy.

PMID- 9637711
TI  - Hypertonicity regulates the function of human neutrophils by modulating
      chemoattractant receptor signaling and activating mitogen-activated protein
      kinase p38.
AB  - Excessive neutrophil activation causes posttraumatic complications, which may be
      reduced with hypertonic saline (HS) resuscitation. We tested if this is because
      of modulated neutrophil function by HS. Clinically relevant hypertonicity (10-25
      mM) suppressed degranulation and superoxide formation in response to fMLP and
      blocked the activation of the mitogen activated protein kinases (MAPK) ERK1/2 and
      p38, but did not affect Ca2+ mobilization. HS did not suppress oxidative burst in
      response to phorbol myristate acetate (PMA). This indicates that HS suppresses
      neutrophil function by intercepting signal pathways upstream of or apart from
      PKC. HS activated p38 by itself and enhanced degranulation in response to PKC
      activation. This enhancement was reduced by inhibition of p38 with SB203580,
      suggesting that p38 up-regulation participates in HS-induced enhancements of
      degranulation. HS had similar effects on the degranulation of cells that were
      previously stimulated with fMLP, but had no effect on its own, suggesting that HS
      enhancement of degranulation requires another signal. We conclude that depending
      on other stimuli, HS can suppress neutrophil activation by intercepting multiple
      receptor signals or augment degranulation by enhancing p38 signaling. In patients
      HS resuscitation may reduce posttraumatic complications by preventing neutrophil
      activation via chemotactic factors released during reperfusion.

PMID- 9637712
TI  - Nitric oxide inhibition induces early activation of type I collagen gene in renal
      resistance vessels and glomeruli in transgenic mice. Role of endothelin.
AB  - Hypertension is often associated with the development of nephroangio- and
      glomerulo-sclerosis. This pathophysiological process is due to increased
      extracellular matrix protein, particularly type I collagen, accumulation. This
      study investigated whether nitric oxide (NO) synthesis is involved in the
      mechanism(s) regulating activation of the collagen I gene in afferent arterioles
      and glomeruli. Experiments were performed on transgenic mice harboring the
      luciferase gene under the control of the collagen I-alpha2 chain promoter
      [procolalpha2(I)]. Measurements of luciferase activity provide highly sensitive
      estimates of collagen I gene activation. NO synthesis was inhibited by NG-nitro-L
      arginine methyl ester (L-NAME) (20 mg/kg per day) for a period of up to 14 wk.
      Systolic blood pressure was increased after 6 wk of treatment (117+/-2 versus
      129+/-2 mmHg, P < 0.01) and reached a plateau after 10 wk (around 160 mmHg).
      Luciferase activity was increased in freshly isolated afferent arterioles and
      glomeruli as early as week 4 of L-NAME treatment (150 and 200% of baseline, P <
      0.01, respectively). The activation of procolalpha2(I) became more pronounced
      with time, and at 14 wk increased four- and tenfold compared with controls in
      afferent arterioles and glomeruli, respectively (P < 0.001). In contrast,
      luciferase activity remained unchanged in aorta and heart up to 8 wk and was
      increased thereafter. Increased histochemical staining for extracellular matrix
      deposition, and particularly of collagen I, was detected in afferent arterioles
      and glomeruli after 10 wk of L-NAME treatment. This fibrogenic process was
      accompanied by an increased urinary excretion rate of endothelin. In separate
      experiments, the stimulatory effect of L-NAME on collagen I gene activation was
      abolished when animals were treated with bosentan, an endothelin receptor
      antagonist. Similarly, bosentan reduced the increased extracellular matrix
      deposition in afferent arterioles and glomeruli during NO inhibition.
      Interestingly, bosentan had no effect on the L-NAME- induced increase of systolic
      pressure. These data indicate that NO inhibition induces an early activation of
      the collagen I gene in afferent arterioles and glomeruli. This activation in the
      kidney precedes the increase in blood pressure and the procolalpha2(I) activation
      in heart and aorta, suggesting a specific renal effect of NO blockade on collagen
      I gene expression that is independent of increased blood pressure and, at least
      partly, mediated through stimulation of the endothelin receptor. Use of
      procolalpha2(I) transgenic mice provides a novel and efficient model to study the
      pathophysiological mechanism(s) regulating renal fibrosis.

PMID- 9637713
TI  - A novel role for ursodeoxycholic acid in inhibiting apoptosis by modulating
      mitochondrial membrane perturbation.
AB  - The hydrophilic bile salt ursodeoxycholic acid (UDCA) protects against the
      membrane-damaging effects associated with hydrophobic bile acids. This study was
      undertaken to (a) determine if UDCA inhibits apoptosis from deoxycholic acid
      (DCA), as well as from ethanol, TGF-beta1, Fas ligand, and okadaic acid; and to
      (b) determine whether mitochondrial membrane perturbation is modulated by UDCA.
      DCA induced significant hepatocyte apoptosis in vivo and in isolated hepatocytes
      determined by terminal transferase-mediated dUTP-digoxigenin nick end-labeling
      assay and nuclear staining, respectively (P < 0.001). Apoptosis in isolated rat
      hepatocytes increased 12-fold after incubation with 0.5% ethanol (P < 0.001). HuH
      7 cells exhibited increased apoptosis with 1 nM TGF-beta1 (P < 0. 001) or DCA at
      >/= 100 microM (P < 0.001), as did Hep G2 cells after incubation with anti-Fas
      antibody (P < 0.001). Finally, incubation with okadaic acid induced significant
      apoptosis in HuH-7, Saos-2, Cos-7, and HeLa cells. Coadministration of UDCA with
      each of the apoptosis-inducing agents was associated with a 50-100% inhibition of
      apoptotic changes (P < 0.001) in all the cell types. Also, UDCA reduced the
      mitochondrial membrane permeability transition (MPT) in isolated mitochondria
      associated with both DCA and phenylarsine oxide by > 40 and 50%, respectively (P
      < 0.001). FACS(R) analysis revealed that the apoptosis-inducing agents decreased
      the mitochondrial transmembrane potential and increased reactive oxygen species
      production (P < 0.05). Coadministration of UDCA was associated with significant
      prevention of mitochondrial membrane alterations in all cell types. The results
      suggest that UDCA plays a central role in modulating the apoptotic threshold in
      both hepatocytes and nonliver cells, and inhibition of MPT is at least one
      pathway by which UDCA protects against apoptosis.

PMID- 9637714
TI  - A truncated cardiac troponin T molecule in transgenic mice suggests multiple
      cellular mechanisms for familial hypertrophic cardiomyopathy.
AB  - Mutations in multiple cardiac sarcomeric proteins including myosin heavy chain
      (MyHC) and cardiac troponin T (cTnT) cause a dominant genetic heart disease,
      familial hypertrophic cardiomyopathy (FHC). Patients with mutations in these two
      genes have quite distinct clinical characteristics. Those with MyHC mutations
      demonstrate more significant and uniform cardiac hypertrophy and a variable
      frequency of sudden death. Patients with cTnT mutations generally exhibit mild or
      no hypertrophy, but a high frequency of sudden death at an early age. To
      understand the basis for these distinctions and to study the pathogenesis of the
      disease, we have created transgenic mice expressing a truncated mouse cTnT allele
      analogous to one found in FHC patients. Mice expressing truncated cTnT at low (<
      5%) levels develop cardiomyopathy and their hearts are significantly smaller (18
      27%) than wild type. These animals also exhibit significant diastolic dysfunction
      and milder systolic dysfunction. Animals that express higher levels of transgene
      protein die within 24 h of birth. Transgenic mouse hearts demonstrate myocellular
      disarray and have a reduced number of cardiac myocytes that are smaller in size.
      These studies suggest that multiple cellular mechanisms result in the human
      disease, which is generally characterized by mild hypertrophy, but, also,
      frequent sudden death.

PMID- 9637715
TI  - Regulation of murine fetal-placental calcium metabolism by the calcium-sensing
      receptor.
AB  - The calcium-sensing receptor (CaSR) regulates PTH secretion to control the
      extracellular calcium concentration in adults, but its role in fetal life is
      unknown. We used CaSR gene knockout mice to investigate the role of the CaSR in
      regulating fetal calcium metabolism. The normal calcium concentration in fetal
      blood is raised above the maternal level, an increase that depends upon PTH
      related peptide (PTHrP). Heterozygous (+/-) and homozygous (-/-) disruption of
      the CaSR caused a further increase in the fetal calcium level. This increase was
      modestly blunted by concomitant disruption of the PTHrP gene and completely
      reversed by disruption of the PTH/ PTHrP receptor gene. Serum levels of PTH and
      1, 25-dihydroxyvitamin D were substantially increased above the normal low fetal
      levels by disruption of the CaSR. The free deoxypyridinoline level was increased
      in the amniotic fluid (urine) of CaSR-/- fetuses; this result suggests that fetal
      bone resorption is increased. Placental calcium transfer was reduced, and renal
      calcium excretion was increased, by disruption of the CaSR. These studies
      indicate that the CaSR normally suppresses PTH secretion in the presence of the
      normal raised (and PTHrP-dependent) fetal calcium level. Disruption of the CaSR
      causes fetal hyperparathyroidism and hypercalcemia, with additional effects on
      placental calcium transfer.

PMID- 9637716
TI  - Characterization of a CD38-like 78-kilodalton soluble protein released from B
      cell lines derived from patients with X-linked agammaglobulinemia.
AB  - Studies on murine B lymphocytes showed that Bruton's tyrosine kinase mediates
      signal transduction induced via CD38, a nonlineage-restricted 45-kD ectoenzyme.
      This signaling is defective in B cells from X-linked immunodeficient mice
      affected with the analogue of human X-linked agammaglobulinemia (XLA). We
      performed a structural and functional analysis of CD38 in XLA and other
      immunodeficiencies, using EBV-immortalized B cells derived from such patients.
      Membrane CD38 was not significantly different from controls in structure, epitope
      density, enzymatic activity, and internalization upon binding of agonistic mAbs.
      Meanwhile, an increased release of soluble CD38 from XLA cells was observed:
      immunoprecipitation from XLA culture media yielded a protein of approximately 78
      kD (p78), reacting also in Western blot and displaying both enzymatic activities
      and a peptide map similar to membrane CD38. Soluble forms and homotypic
      aggregations of CD38 were documented in different cell models and by
      crystallographic analysis of the Aplysia ADP-ribosyl cyclase, the ancestor of
      human CD38. p78 might represent the product of an altered turn-over of membrane
      CD38, a starting point for studying its association with Bruton's tyrosine kinase
      and its role in XLA and other B cell immunodeficiencies.

PMID- 9637717
TI  - Therapeutic levels of human protein C in rats after retroviral vector-mediated
      hepatic gene therapy.
AB  - Protein C deficiency results in a thrombotic disorder that might be treated by
      expressing a normal human protein C (hPC) gene in patients. An amphotropic
      retroviral vector with a liver-specific promoter and the hPC cDNA was delivered
      to rat hepatocytes in vivo during liver regeneration. Expression of hPC varied
      from 55 to 203 ng/ml (1.3-5.0% of normal) for 2 wk after transduction. Expression
      increased to an average of 900 ng/ml (22% of normal) in some rats and was
      maintained at stable levels for 1 yr. All of these rats developed anti-hPC
      antibodies and exhibited a prolonged hPC half-life in vivo. The hPC was
      functional as determined by a chromogenic substrate assay after
      immunoprecipitation. We conclude that most rats achieved hPC levels that would
      prevent purpura fulminans, and that hepatic gene therapy might become a viable
      treatment for patients with severe homozygous hPC deficiency. Anti-hPC antibodies
      increased the hPC half-life and plasma levels in some rats, but did not interfere
      with its functional activity. Thus, the development of antibodies against a
      plasma protein does not necessarily abrogate its biological effect in gene
      therapy experiments.

PMID- 9637718
TI  - Cisplatin-induced apoptosis in rat dorsal root ganglion neurons is associated
      with attempted entry into the cell cycle.
AB  - Platinum compounds induce apoptosis in malignant cells and are used extensively
      in the treatment of cancer. Total dose is limited by development of a sensory
      neuropathy. We now demonstrate that when rats are administered cisplatin (2 mg/kg
      i.p. for 5 d), primary sensory neurons in the dorsal root ganglion die by
      apoptosis. This was reproduced by exposure of dorsal root ganglion neurons and
      PC12 cells to cisplatin (3 microg/ml) in vitro. Apoptosis was confirmed by
      electron microscopy, DNA laddering, and inhibition by the caspase inhibitor z
      VAD.fmk (100 microM). Cell death in vitro was preceded by upregulation of cyclin
      D1, cdk4, and increased phosphorylation of retinoblastoma protein; all are
      indicators of cell cycle advancement. The level of p16(INK4a), an endogenous
      inhibitor of the cyclin D1/cdk4 complex decreased. Exposure of PC12 cells and
      dorsal root ganglion neurons to increased levels of nerve growth factor (100 ng/
      ml) prevented both apoptosis and upregulation of the cell cycle markers. Cancer
      cells without nerve growth factor receptors (gp140TrkA) were not protected by the
      neurotrophin. This indicated that cisplatin may kill cancer cells and neurons by
      a similar mechanism. In postmitotic neurons, this involves an attempt to re-enter
      the cell cycle resulting in apoptosis which is specifically prevented by nerve
      growth factor.

PMID- 9637720
TI  - Right ventricular outflow tract tachycardia due to a somatic cell mutation in G
      protein subunitalphai2.
AB  - Idiopathic ventricular tachycardia is a generic term that describes the various
      forms of ventricular arrhythmias that occur in patients without structural heart
      disease and in the absence of the long QT syndrome. Many of these tachycardias
      are focal in origin, localize to the right ventricular outflow tract (RVOT),
      terminate in response to beta blockers, verapamil, vagal maneuvers, and
      adenosine, and are thought to result from cAMP-mediated triggered activity. DNA
      was prepared from biopsy samples obtained from myocardial tissue from a patient
      with adenosine-insensitive idiopathic ventricular tachycardia arising from the
      RVOT. Genomic sequences of the inhibitory G protein Galphai2 were determined
      after amplification by PCR and subcloning. A point mutation (F200L) in the GTP
      binding domain of the inhibitory G protein Galphai2 was identified in a biopsy
      sample from the arrhythmogenic focus. This mutation was shown to increase
      intracellular cAMP concentration and inhibit suppression of cAMP by adenosine. No
      mutations were detected in Galphai2 sequences from myocardial tissue sampled from
      regions remote from the origin of tachycardia, or from peripheral lymphocytes.
      These findings suggest that somatic cell mutations in the cAMP-dependent signal
      transduction pathway occurring during myocardial development may be responsible
      for some forms of idiopathic ventricular tachycardia.

PMID- 9637719
TI  - Growth factor activation of the estrogen receptor in vascular cells occurs via a
      mitogen-activated protein kinase-independent pathway.
AB  - The classical estrogen receptor ERalpha mediates many of the known cardiovascular
      effects of estrogen and is expressed in male and female vascular cells. Estrogen
      independent activation of ERalpha is known to occur in cells from reproductive
      tissues, but has not been investigated previously in vascular cells. In this
      study, transient transfection assays in human saphenous vein smooth muscle cells
      (HSVSMC) and pulmonary vein endothelial cells (PVEC) demonstrated ERalpha
      dependent activation of estrogen response element-based, and vascular endothelial
      growth factor-based reporter plasmids by both estrogen-deficient FBS (ED-FBS) and
      EGF. In nonvascular cells, ERalpha-mediated gene expression can be activated via
      mitogen-activated protein (MAP) kinase- induced phosphorylation of serine 118 of
      ERalpha. However, in vascular cells, we found that pharmacologic inhibition of
      MAP kinase did not alter EGF-mediated ERalpha activation. In addition, a mutant
      ER containing an alanine-for-serine substitution at position 118 was activated to
      the same degree as the wild-type receptor by ED-FBS and EGF in both HSVSMC and
      PVEC. Furthermore, constitutively active MAP kinase kinase (MAPKK) activated
      ERalpha in Cos1 cells as expected, but MAPKK inhibited ER activation in PVEC. We
      conclude that growth factors also stimulate ERalpha-mediated gene expression in
      vascular cells, but find that this occurs via a MAP kinase-independent pathway
      distinct from that reported previously in nonvascular cells.

PMID- 9637721
TI  - Human circulating eosinophils secrete macrophage migration inhibitory factor
      (MIF). Potential role in asthma.
AB  - Macrophage migration inhibitory factor (MIF) is a potent proinflammatory mediator
      that has been shown to potentiate lethal endotoxemia and to play a potentially
      important regulatory role in human acute respiratory distress syndrome (ARDS). We
      have investigated whether eosinophils are an important source of MIF and whether
      MIF may be involved in the pathophysiology of asthma. Unstimulated human
      circulating eosinophils were found to contain preformed MIF. Stimulation of human
      eosinophils with phorbol myristate acetate in vitro yielded significant release
      of MIF protein. For example, eosinophils stimulated with phorbol myristate
      acetate (100 nM, 8 h, 37 degreesC) released 1,539+/-435 pg/10(6) cells of MIF,
      whereas unstimulated cells released barely detectable levels (< 142 pg/10(6)
      cells, mean+/-SEM, n = 8). This stimulated release was shown to be (a)
      concentration- and time-dependent, (b) partially blocked by the protein synthesis
      inhibitor cycloheximide, and (c) significantly inhibited by the protein kinase C
      inhibitor Ro-31,8220. In addition, we show that the physiological stimuli C5a and
      IL-5 also cause significant MIF release. Furthermore, bronchoalveolar lavage
      fluid obtained from asthmatic patients contains significantly elevated levels of
      MIF as compared to nonatopic normal volunteers (asthmatic, 797.5+/-92 pg/ml;
      controls, 274+/-91 pg/ml). These results highlight the potential importance of
      MIF in asthma and other eosinophil-dependent inflammatory disorders.

PMID- 9637722
TI  - Phenylketonuria. The in vivo hydroxylation rate of phenylalanine into tyrosine is
      decreased.
AB  - In phenylketonuria (PKU), the enzyme phenylalanine hydroxylase is deficient,
      resulting in a decreased conversion of phenylalanine (Phe) into tyrosine (Tyr).
      The severity of the disease is expressed as the tolerance for Phe at 5 yr of age.
      In PKU patients it is assumed that the decreased conversion of Phe into Tyr is
      directly correlated with the tolerance for Phe. We investigated this correlation
      by an in vivo stable isotope study. The in vivo residual hydroxylation was
      quantitated using a primed continuous infusion of L-[ring- 2H5]Phe and L-[1
      13C]Tyr and the determination of the isotopic enrichments of L-[ring-2H5]Phe, L
      [ring-2H4]Tyr, and L-[1-13C]Tyr in plasma. Previous reports by Thompson and
      coworkers (Thompson, G.N., and D. Halliday. 1990. J. Clin. Invest. 86:317-322;
      Thompson, G.N., J.H. Walter, J.V. Leonard, and D. Halliday. 1990. Metabolism.
      39:799-807; Treacy, E., J.J. Pitt, K. Seller, G.N. Thompson, S. Ramus, and R.G.H.
      Cotton. 1996. J. Inherited Metab. Dis. 19:595- 602), applying the same technique,
      showed normal in vivo hydroxylation rates of Phe in almost all PKU patients.
      Therefore, our study was divided up in two parts. First, the method was re
      evaluated. Second, the correlation between the in vivo hydroxylation of Phe and
      the tolerance for Phe was tested in seven classical PKU patients. Very low (0.13-
      0.95 micromol/kg per hour) and normal (4.11 and 6.33 micromol/kg per hour)
      conversion rates were found in patients and controls, respectively. Performing
      the infusion study twice in the same patient and wash-out studies of the labels
      at the end of the experiment in a patient and control showed that the method is
      applicable in PKU patients and gives consistent data. No significant correlation
      was observed between the in vivo hydroxylation rates and the tolerances. The
      results of this study, therefore, showed that within the group of patients with
      classical PKU, the tolerance does not depend on the in vivo hydroxylation.

PMID- 9637723
TI  - Endothelin-1 is synthesized and inhibits cyclic adenosine monophosphate-
      dependent anion secretion by an autocrine/paracrine mechanism in gallbladder
      epithelial cells.
AB  - Ion and fluid transport across the biliary epithelium contributes to bile
      secretion. Since endothelin (ET)-1 affects ion transport activities and is
      released by human gallbladder- derived biliary epithelial cells in primary
      culture, we examined the expression of ET peptides and ET receptors and the
      influence of ET-1 on ion transport in this epithelium ex vivo. In freshly
      isolated gallbladder epithelial cells, preproET-1, -2, and -3 mRNAs were detected
      by reverse transcription PCR and ET-1 isopeptide was identified by
      chromatography. The cells also displayed ET receptor mRNAs and high-affinity
      binding sites for ET-1, mostly of the ETB type. Electrogenic anion secretion
      across intact gallbladder mucosa was stimulated by forskolin, secretin, and
      exogenous ATP, as assessed by short-circuit current (Isc) increases in Ussing
      type chambers. ET-1 inhibited forskolin- and secretin-induced changes in Isc,
      without affecting baseline Isc or ATP-induced changes. Accordingly, ET-1
      significantly reduced the accumulation of intracellular cAMP elicited by
      forskolin and secretin in the epithelial cells, and this effect was abolished by
      pertussis toxin. This is the first evidence that ET-1 is synthesized and
      inhibits, via a Gi protein-coupled receptor, cAMP-dependent anion secretion in
      human gallbladder epithelium, indicating a role in the control of bile secretion
      by an autocrine/paracrine mechanism.

PMID- 9637724
TI  - Tolerance induction ameliorates allograft vasculopathy in rat aortic transplants.
      Influence of Fas-mediated apoptosis.
AB  - Based on successful induction of donor-specific unresponsiveness by alloantigenic
      stimulation in several animal models of acute rejection, we hypothesized that
      similar immune manipulations would also inhibit the evolution of chronic
      rejection and transplant vasculopathy. To induce immune tolerance, DA rats
      received a PVG heart allograft and were immunosuppressed with cyclosporine for 30
      d. At day 100 the animals were challenged with a PVG aortic allograft after
      either 1 or 18 h of cold ischemia. 8 wk after the aortic transplantation, the
      grafts were investigated for morphological changes, infiltrating cells,
      apoptosis, and Fas-Fas ligand expression. Control allografts showed advanced
      transplant arteriosclerosis, whereas tolerance-induced aortic allografts
      displayed reduced neointimal formation, less medial atrophy, fewer apoptotic
      cells, and fewer Fas- and FasL-expressing cells. Prolonged ischemic storage time
      did not profoundly alter the morphological changes of the allografts. Fas
      expression was found in T cells, macrophages, vascular smooth muscle cells, and
      endothelial cells, whereas FasL was expressed mainly by T cells and macrophages.
      FasL mRNA expression was evident throughout the entire allograft wall. In
      conclusion, induction of allospecific tolerance can effectively prevent
      transplant arteriosclerosis. Cold ischemia damage does not abrogate the
      beneficial effect of tolerance, but creates a separate identity of mainly
      endothelial lesions. Furthermore, Fas-mediated apoptosis appears to be involved
      in the pathological lesions seen in chronic rejection.

PMID- 9637725
TI  - A novel form of hereditary myeloperoxidase deficiency linked to endoplasmic
      reticulum/proteasome degradation.
AB  - Myeloperoxidase (MPO) deficiency is a common inherited disorder linked to
      increased susceptibility to infection and malignancy. We identified a novel
      missense mutation in the MPO gene at codon 173 whereby tyrosine is replaced with
      cysteine (Y173C) that is associated with MPO deficiency and assessed its impact
      on MPO processing and targeting in transfectants expressing normal or mutant
      proteins. Although the precursor synthesized by cells expressing the Y173C
      mutation (MPOY173C) was glycosylated, associated with the molecular chaperones
      calreticulin and calnexin, and acquired heme, it was neither proteolytically
      processed to mature MPO subunits nor secreted. After prolonged association with
      calreticulin and calnexin in the endoplasmic reticulum, MPOY173C was degraded.
      Furthermore, the 20S proteasome inhibitor N-acetyl-L-leucinyl-L-leucinyl-L
      norleucinyl inhibited its degradation, suggesting that the proteasome mediates
      proteolysis of MPOY173C and, thus, participates in quality control in this novel
      form of hereditary MPO deficiency.

PMID- 9637726
TI  - Polyclonal antibody directed against human RANTES ameliorates disease in the
      Lewis rat adjuvant-induced arthritis model.
AB  - Adjuvant-induced arthritis (AIA) is one of many animal models of rheumatoid
      arthritis, a disease characterized by a T-lymphocyte and macrophage cellular
      infiltrate. We have characterized the development of this disease model with
      respect to chemokine expression. Increased levels of two chemokines, RANTES, a T
      lymphocyte and monocyte chemo-attractant, and KC a chemoattractant for
      neutrophils, were found in whole blood and in the joint. Surprisingly, levels of
      MIP-1alpha, another T-lymphocyte and monocyte chemoattractant, were unchanged
      throughout the course of the disease in whole blood and only slightly elevated in
      the joint. RANTES expression plays an important role in the disease since a
      polyclonal antibody to RANTES greatly ameliorated symptoms in animals induced for
      AIA and was found to be as efficacious as treatment with indomethacin, a non
      steroidal anti inflammatory. Polyclonal antibodies to either MIP-1alpha or KC
      were ineffective. This is the first report to show the importance of RANTES in
      the development of AIA.

PMID- 9637727
TI  - Induction of CYP1A1, but not CYP1A2, in adrenals of 3, 3'-methylcholanthrene
      treated guinea pigs.
AB  - To test the inducibility of CYP1A homologs in guinea pig adrenal, the effects of
      3,3'-methylcholanthrene, an archetypal inducer of CYP1A, were compared in guinea
      pig adrenal and liver. Western blot analysis showed that levels of both CYP1A1
      (53 kDa) and CYP1A2 (56 kDa) increasedin liver microsomes of 3,3'
      methylcholanthrene-treated guinea pigs. In adrenals, an immunoreactive protein
      comigrating with liver CYP1A1 was detected only after 3,3'-methylcholanthrene
      treatment. Protein comigrating with CYP1A2 was never detected in adrenal
      microsomes. A third inducible immunoreactive protein (57 kDa) was seen in liver,
      but not adrenal, after 3, 3'-methylcholanthrene treatment. Another immunoreactive
      protein (52 kDa), present constitutively in liver and adrenal microsomes, was not
      induced in either tissue by 3,3'-methylcholanthrene. The precise identities of
      the inducible 57-kDa and the noninducible 52-kDa proteins remain to be
      determined. However, the identity of the 53-kDa protein in the adrenal as CYP1A1
      was confirmed by RT-PCR, Northern blot, and sequence analysis. Similar analyses
      demonstrated that, despite the fact that the 56-kDa protein was not detectable in
      adrenal microsomes, CYP1A2 mRNA was present in adrenals of control animals.
      Strikingly, CYP1A2 mRNA decreased in adrenal, but increased in liver, following
      3,3'-methylcholanthrene treatment, underscoring differences in the regulation of
      CYP1A expression in the two tissues. Levels of ethoxyresorufin and
      methyoxyresorufin metabolism correlated with levels of CYP1A1 and CYP1A2 protein,
      respectively.

PMID- 9637728
TI  - Two unusual amino acid substitutions in cytochrome b of the colorless alga
      Polytomella spp.: correlation with the atypical spectral properties of the bH
      heme.
AB  - The dithionite-reduced spectra of the purified bc1 complexes from the colorless
      alga Polytomella spp. and the closely related green alga Chlamydomonas
      reinhardtii were compared. The spectrum of the bc1 complex from C. reinhardtii
      showed a profile similar to those of the bc1 complexes from other species. In
      contrast, the bc1 complex from Polytomella spp. exhibits a double-peak spectrum
      in the alpha-band region, where the absorption bands of cytochrome c1 and
      cytochrome b are completely resolved. To further understand the molecular basis
      of these spectroscopic differences, the mitochondrial gene encoding cytochrome b
      of Polytomella spp. was cloned, sequenced, and compared with that of C.
      reinhardtii. The Polytomella spp. cytochrome b gene is 1113 bp long and does not
      contain introns. The deduced protein sequence exhibits 56% identity and 68%
      similarity with the cytochrome b of C. reinhardtii, and in a phylogenetic
      analysis it clearly affiliated with the b-type cytochromes of C. reinhardtii and
      C. smithii. A comparison of the primary sequences of the Polytomella spp.
      cytochrome b with other b-type cytochromes, and its analysis based on the
      structure featuring eight transmembrane stretches, allowed the identification of
      a tyrosine in position 114, which substitutes for a tryptophan present in all
      mitochondrial b-type cytochromes sequenced to date. In addition, the primary
      sequence of the cytochrome b from Polytomella spp. has a serine at position 36,
      instead of a nonpolar residue (alanine or leucine) found in all other species. In
      the proposed model for cytochrome b, both residues Tyr114 and Ser36 are in close
      proximity to the high-potential bH heme. The above data suggest that the polar
      residues Y114 and S36, each one by itself or in combination, may interact with
      heme bH of Polytomella spp. and, thus, may be responsible for the unique
      spectroscopic characteristics of cytochrome b.

PMID- 9637729
TI  - Role of allosteric: zinc interdomain region of the regulatory subunit in the
      allosteric regulation of aspartate transcarbamoylase from Escherichia coli.
AB  - The hydrophobic interface between the allosteric and the zinc domains of the
      regulatory subunit of aspartate transcarbamoylase has previously been implicated
      in the heterotropic ATP activation of the enzyme. The present work shows that
      this interface also affects CTP and CTP-UTP inhibition and proposes a structural
      explanation for the effects. Mutant enzymes derived from nonselective mutagenesis
      of residues r101-r106 (residues that contribute part of the interface) displayed
      a variety of homotropic and heterotropic effects. The cooperative behavior of the
      enzymes was affected, as indicated by reduced aspartate S0.5 values and apparent
      Hill coefficient values for V106L, V106L/N105S, and I103F/R102C. In addition,
      both ATP activation and CTP inhibition were significantly reduced and CTP+UTP
      synergistic inhibition was decreased in these mutants. The D104G mutant enzyme
      was subject to inhibition by CTP andCTP+UTP, but was not activated by ATP.
      Finally, the I103T mutant enzyme had an increased S0.5 value of 11.5 mM and
      displayed altered effector responses: ATP acted as an inhibitor, and the CTP+UTP
      synergistic inhibition was reduced. Most of these allosteric variations can be
      explained in terms of perturbations to the "tongue and groove" hydrophobic
      interface between the allosteric and the zinc domains and a consequent impact on
      a second interface ("reg1:cat4") between regulatory and catalytic subunits.

PMID- 9637730
TI  - Inhibition of protein tyrosine phosphatases PTP1B and CD45 by sulfotyrosyl
      peptides.
AB  - Sulfotyrosyl peptides corresponding to the known high-affinity substrate
      phosphotyrosyl peptide sequences in casein and the autophosphorylation sites of
      insulin receptor and EGF receptor were investigated as inhibitors of protein
      tyrosine phosphatases PTP1B and CD45. These peptides inhibit both PTP1B and CD45
      in the micromolar range competitively and reversibly. The elements required for
      inhibition were investigated by truncation and substitution of these peptides.
      Acidic residues N-terminal to the sulfotyrosyl residues are essential for high
      affinity binding to PTP1B. The recognition elements required for inhibition of
      PTP1B and CD45 are different and this suggests the possibility of identifying
      selective active-site-directed inhibitors for these enzymes.

PMID- 9637731
TI  - Purification, characterization, and amino acid sequence determination of
      acanthins, potent inhibitors of platelet aggregation from Acanthophis antarcticus
      (common death adder) venom.
AB  - Venom of Acanthophis antarcticus, a common death adder, exhibits potent
      antiplatelet effects. By a combination of gel-filtration, cation-exchange, and
      reversed-phase chromatographic methods, two inhibitors of platelet aggregation,
      named acanthin I and II, were purified to homogeneity as assessed by capillary
      electrophoresis and electrospray mass spectrometry. These isoforms exhibit the
      most potent antiplatelet activity known thus far, with IC50 values of 7 nM for
      acanthin I and 4 nM for acanthin II in human whole blood when collagen was used
      as an agonist, whereas with ADP the IC50 values were 10 and 12 nM, respectively.
      Acanthin I and II are basic proteins with pIs of 10.2 +/- 0.1 and 10.4 +/- 0.1
      and molecular weights of 12,844.58 +/- 0.61 and 12,895.63 +/- 0.48, respectively,
      as determined by electrospray mass spectrometry. They exhibit phospholipase
      enzyme activity, and acanthin I and II hydrolyzed 51. 57 +/- 1.30 and 46.85 +/-
      2.90 micromol of phosphatidylcholine/min/mg, respectively. The complete amino
      acid sequences of acanthin I and II showed that they have a high homology with
      each other and with other elapids' phospholipase A2 neurotoxin, especially
      pseudexin A.

PMID- 9637732
TI  - Isolation, sequence analysis, and biological activity of atrolysin E/D, the non
      RGD disintegrin domain from Crotalus atrox venom.
AB  - Crotalid snake venom metalloproteinases often have associated with them
      nonproteinase domains that may be processed from the mature proteinases. Nascent
      atrolysin E, from the western diamondback rattlesnake, Crotalus atrox, has a
      metalloproteinasedomain and a non-RGD disintegrin domain that is lacking in the
      mature metalloproteinase. In this studywe report on the isolation, sequence
      analysis, andbiological activity of the 7.4-kDa atrolysin E disintegrin domain
      (atrolysin E/D). Atrolysin E/D represents approximately 0.2% of the total protein
      fromthe crude venom. The protein begins with a glycinyl residue found in the
      latter part of the spacer region. The sequence of atrolysin E/D is identical to
      thatof the non-RGD disintegrin domain of atrolysin E. The structure is termed a
      non-RGD disintegrin sincein lieu of the characteristic RGD sequence, a Met-Val
      Asp (MVD) is found instead. Nevertheless, the protein is a potent inhibitor of
      both collagen- and ADP-stimulated platelet aggregation with IC50 values of 4 and
      8 nM, respectively. A cyclized synthetic peptide, Ac-CRVSMVDRNDDTC-NH2, which
      represents the sequence of the atrolysin E/D non-RGD loop, was demonstrated to be
      an effective inhibitor of platelet aggregation. Therefore, this region of
      atrolysin E/D's structure, as in the disintegrins proper, is important for the
      biological activity of the protein. Thus, like the non-RGD disintegrin barbourin
      from Sistrurus miliarius barbouri, a RGD sequence in the context of the
      disintegrin protein backbone is not an absolute requirement for platelet
      aggregation inhibitory activity. These data underscore the biochemical and
      functional complexity of crotalid snake venoms due to differential proteolytic
      processing of the precursor metalloproteinases and exemplify how the processed
      fragments may contribute to the observed pathological effects of the venom.

PMID- 9637733
TI  - Expression and characterization of human glutamate-cysteine ligase.
AB  - Glutamate-cysteine ligase (GLCL) catalyzes the rate-limiting step in glutathione
      biosynthesis. GLCL comprises regulatory (GLCLR) and catalytic (GLCLC) subunits.
      To understand better the structure-function relationship of GLCL subunits and
      holoenzyme, human GLCLR and GLCLC genes were inserted into the baculovirus
      genome. Recombinant hGLCLR andhGLCLC were produced in cells infected with
      recombinant baculoviruses, and homogeneous hGLCL subunits and holoenzyme were
      purified from cell lysates with a Ni-NTA resin. Purified recombinant hGLCL
      holoenzyme was catalytically more active than hGLCLC with L-glutamate, L-alpha
      aminobutyrate, and ATP as substrates. The selectivity of purified hGLCL
      holoenzyme for L-glutamate, L-alpha-aminobutyrate, or L-cysteine was
      significantly higher than for hGLCLC. Glutathione was a noncompetitive inhibitor
      for both hGLCL holoenzyme and hGLCLC. hGLCLC was more sensitive to inhibition by
      glutathione than hGLCL holoenzyme. Deletion of the first 25 amino acid residues
      at the amino terminus of GLCLC dramatically decreased GLCL activity, indicating
      that the amino terminus of GLCLC is required for full catalytic activity.
      Expressed and purified hGLCL provides a useful tool to investigate glutathione
      biosynthesis in vitro.

PMID- 9637734
TI  - cAMP does not inhibit convulxin-induced tyrosyl-phosphorylation of human platelet
      proteins, including PLCgamma2, but completely blocks the integrin alphaIIb beta3
      dependent dephosphorylation step: comparisons with RGDS peptide, cytochalasin D,
      and phenylarsine oxide.
AB  - Convulxin (Cvx) isolated from Crotalus durissus terrificus venom, induces
      platelet aggregation, phospholipase C (PLC) activation, and tyrosyl
      phosphorylation (PTP) of multiple proteins, including PLCgamma2 by a mechanism
      independent of integrin alphaIIb beta3. However, PTP induced by Cvx is followed
      by a dephosphorylation step in a platelet aggregation-dependent manner. Here we
      show that increasing intraplatelet content of cAMP with forskolin is associated
      with the inhibition of Cvx-induced platelet aggregation, ATP secretion, and
      inositol-phosphates production. However, the early onset of Cvx-induced PTP is
      not sensitive to cAMP (including PLCgamma2), and it also occurs in the presence
      of integrin alphaIIb beta3-antagonist (RGDS peptide, RGDS) or inhibitors of actin
      polymerization (cytochalasin D, CD) and tyrosine-phosphatases (phenylarsine
      oxide, PAO). However, forskolin, RGDS, and CD prevented the dephosphorylation
      step together with inhibition of platelet aggregation, whereas in the presence of
      phenylarsine oxide (PAO) the dephosphorylation step was replaced by an increase
      in the number and intensity of tyrosyl-phosphorylated proteins. Our data provide
      evidence to conclude that (i) cAMP inhibits platelet aggregation at a downstream
      site to PLCgamma2 tyrosyl-phosphorylation; (ii) Cvx-induced PTP is independent on
      integrin alphaIIb beta3 engagement, actin polymerization, and tyrosine
      phosphatases activation; (iii) integrin alphaIIb beta3 mediates the
      dephosphorylation step in a platelet aggregation-dependent manner; and (iv) Cvx
      and collagen stimulate platelets by a similar signal transduction pathway.

PMID- 9637735
TI  - Reasoning enantioselectivity and kinetics of seleno-subtilisin from the
      subtilisin template.
AB  - The active-site serine (Ser221) of subtilisin Carlsberg(from Bacillus
      licheniformis) and subtilisin BPN' (fromBacillus amyloliquefaciens) was
      chemically converted into a selenocystein. Contrary to subtilisin's protease
      activity the semisynthetic seleno-subtilisin catalyzed the reduction of
      hydroperoxides. Enantioselectivity and kinetics of this reaction were studied by
      kinetic resolution of five racemic alkyl aryl hydroperoxides catalyzed by the
      seleno-subtilisin variants. Due to the identical tertiary structure of subtilisin
      and seleno-subtilisin, the enzymes have comparable substrate binding properties.
      Thus, a rational screening for suitable peroxidase substrates featuring
      structural characteristics of known subtilisin substrates was enabled. The
      enantioselective recognition of (S)-configured alkyl aryl hydroperoxides by
      seleno-subtilisin was comprehensible by subtilisin's preference for comparable
      (S)-alkyl aryl amines or alcohols. The analysis of chiral products by
      multidimensional gas chromatography revealed enantiomeric excesses up to 98%.
      Kinetics of seleno-subtilisin were rationalized on the basis of the established
      substrate-catalyst interactions of the subtilisin framework. The Carlsberg and
      BPN' peroxidase variants revealed typical differences in turnover numbers (kcat)
      and Michaelis-Menten affinity constants (Km) already known from subtilisin
      variants. Turnover numbers of seleno-subtilisin BPN' were lower and Km values
      were higher in comparison to Carlsberg variant. Substrate affinity of several
      substituted 1-arylethyl hydroperoxides to seleno-subtilisin was reasonable in
      comparison to corresponding aryl boronic acid inhibitors of subtilisin.

PMID- 9637736
TI  - An examination of the role of increased cytosolic free Ca2+ concentrations in the
      inhibition of mRNA translation.
AB  - Mobilization of Ca2+ sequestered by the endoplasmic reticulum (ER) produces the
      phosphorylation of initiation factor (eIF) 2, whereas an increase in cytosolic
      free Ca2+ ([Ca2+]i) due to plasmalemmal Ca2+ influx increases the phosphorylation
      of elongation factor (eEF) 2. In nucleated mammalian cells, depletion of ER Ca2+
      stores has been demonstrated to inhibit translational initiation, but evidence
      that increased [Ca2+]i per se causes slowing of peptide chain elongation is
      lacking. L-type Ca2+ channel activity of GH3 pituitary cells, which are enriched
      in calmodulin-dependent eEF-2 kinase, was manipulated such that the impact of
      [Ca2+]i on eEF-2 phosphorylation and translational rate could be examined for up
      to 10 min without inhibiting initiation. At 1 mM extracellular Ca2+, resting
      [Ca2+]i values were high (154-255 nM) and eEF-2 was phosphorylated. The Ca2+
      channel antagonist, nisoldipine, lowered [Ca2+]i and reduced eEF-2
      phosphorylation by half but had no effect on amino acid incorporation. The Ca2+
      channel agonist, Bay K 8644, produced sustained elevations of [Ca2+]i that were
      associated with 25-50% increases in eEF-2 phosphorylation, but no changes in
      protein synthetic rates occurred. Larger Ca2+ influxes were achievable with
      either 25 mM KCl or KCl plus Bay K 8644. These treatments further increased eEF-2
      phosphorylation (50-100% above control) and inhibited leucine incorporation by 20
      70% but ATP content was reduced by 25-50% and total cell-associated Ca2+ contents
      rose by 3- to 13-fold. eIF-2alpha was not phosphorylated during these treatments.
      Addition of low concentrations of ionomycin, which do not lower ATP content, was
      associated with complex changes in [Ca2+]i that resembled alterations in eEF-2
      phosphorylation. The inhibition of leucine incorporation in response to
      ionomycin, however, coincided only with the phosphorylation of eIF-2alpha, not
      eEF-2. It is concluded that changes in [Ca2+]i occurring in the absence of ATP
      depletion alter the phosphorylation state of eEF-2 but are not regulatory for
      mRNA translation.

PMID- 9637737
TI  - The PutA protein of Salmonella typhimurium catalyzes the two steps of proline
      degradation via a leaky channel.
AB  - Proline utilization in Salmonella typhimurium requires two proteins encoded by
      the put operon: PutP, the major proline permease, and PutA. PutA is a
      multifunctional, peripheral membrane protein which acts both as a transcriptional
      repressor for the put operon and enzyme catalyzing the two-step conversion of
      proline to glutamate. In the first enzymatic reaction catalyzed by PutA, proline
      oxidation to pyrroline-5-carboxylate (P5C) is coupled with the reduction of a
      tightly associated FAD. In the second reaction, P5C oxidation to glutamate is
      coupled with reduction of soluble NAD. Although PutA can use exogenous P5C, the
      concentration of exogenous P5C required for the P5C dehydrogenase reaction is
      much greater than the steady-state P5C concentration accumulated during proline
      degradation. Furthermore, exogenous P5C does not efficiently compete against
      endogenous P5C for the production of glutamate, and the endogenous P5C produced
      directly from proline is preferentially used by PutA for the production of
      glutamate. Kinetic assays indicate that in the presence of NAD the two enzymatic
      reactions of PutA function synchronously to increase the overall reaction rate
      over that of the two independent reactions, and the second reaction proceeds in
      the absence of a lag phase. These results indicate that PutA directly transfers
      the intermediate P5C between the two enzymatic functions via a "leaky channel"
      mechanism. Because both the reduction of FAD and the intermediate P5C stimulate
      membrane association of PutA, channeling of P5C may also contribute to the
      regulation of proline utilization.

PMID- 9637738
TI  - High-level expression of RXRalpha and the presence of endogenous ligands
      contribute to expression of a peroxisome proliferator-activated receptor
      responsive gene in hepatoma cells.
AB  - Genes containing peroxisome proliferator-activated receptor (PPAR) binding sites
      are both inducible by peroxisome proliferators and expressed in a tissue-specific
      fashion. A PPAR-responsive reporter gene cotransfected with a PPARalpha
      expression vector was highly expressed in H4IIEC3 hepatoma cells. Addition of
      clofibrate resulted in a modest further induction of the reporter gene. In CV-1
      cells, high expression of the reporter required the addition of clofibrate.
      H4IIEC3 cells had higher levels of retinoid X receptor (RXRalpha) than CV-1
      cells; cotransfection of CV-1 cells with PPARalpha plus RXRalpha expression
      plasmids abolished the cell line difference in basal and clofibrate-stimulated
      expression of the reporter. Lipid extracts of hepatoma cells or of liver or
      kidney stimulated expression of the reporter; extracts of CV-1 cells were far
      less effective. Chromatographic analysis of these extracts revealed high levels
      of three fractions of lipid in liver and H4IIEC3 cells that were lower in CV-1
      cells. We conclude that (1) in cells expressing high levels of both RXRs and
      PPARalpha, such as hepatocytes and kidney cells, these factors are constitutively
      active; (2) activators of PPARalpha may increase its ability to form heterodimers
      with RXRs when the latter are limiting; and (3) hepatoma cells, liver, and kidney
      contain lipid-extractable compounds capable of activating PPARalpha.

PMID- 9637739
TI  - Mechanism-based inactivation of cytochromes P450 2E1 and 2B1 by 5-phenyl-1
      pentyne.
AB  - A series of acetylenic compounds whose structures were based on "P450 2E1-like"
      substrates was investigated for their ability to cause inactivation of P450 2E1
      dependent p-nitrophenol hydroxylation. The most effective compound with liver
      microsomes from pyridine-treated rats or with rabbit P450 2E1 in a reconstituted
      system was 5-phenyl-1-pentyne. The inactivation of purified 2B1, 2E1, a truncated
      2E1 lacking amino acids 3-29, 2E1(Delta3-29), or a truncated 2E1 in which
      threonine 303 was replaced with alanine, 2E1(Delta3-29, T303A), in a
      reconstituted system by 5-phenyl-1-pentyne was NADPH- and time-dependent and
      followed pseudo-first-order kinetics. The maximal rate constants for
      inactivation, the concentrations that gave half-maximal inactivation (KI), and
      the partition ratios (the number of 5-phenylvaleric acid molecules
      formed/inactivation event) were determined with each P450. The KI values for 2B1
      and 2E1(Delta3-29, T303A) were twice those for 2E1 and 2E1(Delta3-29), and the
      partition ratios for 2B1 and 2E1(Delta3-29, T303A) were 5-10 times greater than
      those of 2E1 or 2E1(Delta3-29). During the incubation of P450 2E1 with 5-phenyl-1
      pentyne, the loss of P450 as determined by the reduced-CO difference spectra was
      equal to the loss of catalytic activity. The formation of a heme adduct was
      demonstrated by HPLC analysis of reaction mixtures containing 5-[3H]phenyl-1
      pentyne. HPLC analysis with diode-array detection showed that the Soret region of
      the proposed heme adduct was different from that of the unmodified heme. The HPLC
      peak containing the proposed heme adduct was further analyzed by matrix-assisted
      laser desorption ionization mass spectrometry, and the resulting peaks could
      result from the addition of a 2-oxo-5-phenylpentyl group to the heme.

PMID- 9637740
TI  - Accumulation of various N-acylethanolamines including N-arachidonoylethanolamine
      (anandamide) in cadmium chloride-administered rat testis.
AB  - Changes in the levels of various molecular species of N-acylethanolamine in CdCl2
      administered rat testis were examined. We found that the levels of various N
      acylethanolamines including anandamide (N-arachidonoylethanolamine), an
      endogenous cannabinoid receptor ligand, were dramatically increased in CdCl2
      admin-istered rat testis. Such changes were particularlyprominent for saturated
      and monoenoic species such as N-palmitoyl species (39-fold at 9 h) and N-stearoyl
      species (21-fold at 9 h), compared with unsaturated fatty acid-containing species
      such as anandamide (5-fold at 9 h). Noticeably, increased levels were observed of
      not only N-acylethanolamines but also several species of N
      acylphosphatidylethanolamine, potential precursors for N-acylethanolamines. We
      confirmed that the rat testis microsomal fraction contains phosphodiesterase
      activity catalyzing the release of N-acylethanolamine from N
      acylphosphatidylethanolamine and transacylase activity catalyzing the formation
      of N-acylphosphatidylethanolamine from phosphatidylethanolamine and
      phosphatidylcholine. These enzyme activities were not dramatically different in
      the microsomal fraction obtained from CdCl2-administered rat testis compared with
      that in the case of control rat testis, at least when estimated in cell-free
      assay systems, suggesting that the accessibility of the substrates to the enzymes
      may be increased in CdCl2-administered rat testis to generate a large amount of N
      acylethanolamine. Possible pathophysiological implications of the augmented
      generation of N-acylethanolamine including anandamide in CdCl2-administered rat
      testis were discussed.

PMID- 9637741
TI  - Radiation inactivation suggests that human multidrug resistance-associated
      protein 1 occurs as a dimer in the human erythrocyte membrane.
AB  - Molecular masses of functional units of two components of 2, 4-dinitrophenyl-S
      glutathione (DNP-SG) transport across the erythrocyte membrane determined by
      radiation inactivation were 437 +/- 69 kDa for the high-affinity component and
      466 +/- 67 kDa for the low-affinity component. These results confirm that the
      multidrug resistance-associated protein (MRP) 1 is responsible for the high
      affinity DNP-SG transport across the erythrocyte membrane and suggest that MRP1
      exists in the membrane as a dimer. The molecular size of the low-affinity
      transporter is similar if not identical to that of MRP1. Moreover, while the
      molecular mass of the DNP-SG-ATPase activity of the erythrocyte membrane
      corresponds also to that of MRP (375 +/- 36 kDa), the molecular mass of the
      functional unit of dinitrophenol-stimulated ATPase is significantly lower (232 +/
      26 kDa), which suggests that thisactivity is linked to a different protein,
      perhapsaminophospholipid translocase.

PMID- 9637742
TI  - Dietary cholesterol regulates hepatic 3-hydroxy-3-methylglutaryl coenzyme A
      reductase gene expression in rats primarily at the level of translation.
AB  - The level of gene expression at which dietary cholesterol exerts feedback
      regulation on hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase
      was investigated using young male Sprague-Dawley rats. Previous studies suggested
      that this regulation might be exerted posttranscriptionally. Thus, possible
      regulation at the levels of catalytic efficiency, protein turnover, and
      translation was investigated. To examine possible regulation at the level of
      catalytic efficiency, rats were placed on chow diets supplemented with 2%
      cholesterol and the rates of decline in hepatic HMG-CoA reductase activity and
      immunoreactive protein levels were determined. Both decreased slowly over a 72-h
      period. The catalytic efficiency did not change. These observations are
      inconsistent with phosphorylation-dephosphorylation or thiol-disulfide
      interchange as possible mechanisms. The possibility that dietary cholesterol
      might act by increasing the rate of turnover of HMG-CoA reductase protein was
      examined by determining the half-life of the enzyme in livers from rats consuming
      chow or chow supplemented with 2% cholesterol. The half-life of HMG-CoA reductase
      protein was not decreased in the animals receiving cholesterol, thus ruling out
      this possibility. Regulation at the level of translation was investigated by
      measuring the rate of HMG-CoA reductase protein synthesis in liver slices using
      [35S]methionine and [35S]cysteine. It was found that the rate of synthesis was
      reduced by over 80% in liver slices from rats fed a diet supplemented with 2%
      cholesterol. Similar results were obtained with liver slices from rats given
      mevalonolactone, which supplies both sterol and nonsterol endproducts. These
      results indicate that cholesterol regulates hepatic HMG-CoA reductase gene
      expression in rats primarily at the level of translation.

PMID- 9637743
TI  - NF-AT-luciferase reporter T cell lines as tools to screen immunosuppressive
      drugs.
AB  - The development of safer analogues of immunosuppressants such as cyclosporin A
      and FK506 is an important goal for a number of clinical applications ranging from
      transplantation to the treatment of autoimmune diseases. Here we show the
      generation and the characterization of Jurkat T cell lines stably transfected
      with a reporter construct containing the firefly luciferase gene under the
      control of NF-AT. These lines specifically respond in a cyclosporin A-sensitive
      manner to T cell antigen receptor-derived signals. Due to the high levels of
      luciferase activity expression fewer than 1000 cells are required for detection
      of luciferase. In addition, a simplified luciferase assay allows to reduce both
      the manipulations and the time required for the assay, making these lines
      potentially useful models for the automated screening of cyclosporin A and FK506
      analogues.

PMID- 9637744
TI  - Evaluation of the safety and immunogenicity of a new, heat-treated human rabies
      immune globulin using a sham, post-exposure prophylaxis of rabies.
AB  - A double-blind, controlled, randomized trial was conducted to evaluate the safety
      and immunogenicity of a new human rabies immune globulin (HTRIG). This product,
      manufactured by Pasteur Merieux Connaught, PMC, has undergone a heat-treatment
      step (10 h at 60 degrees C) and removal of mercurothiolate. The corresponding
      unheated product available from the same manufacturer (human rabies immune
      globulin, HRIG, IMOGAM RABIES[spr2]) was used for comparison. These two rabies
      immune globulins (RIGs) were administered either alone or in association with the
      human diploid cell rabies vaccine (HDCV, IMOVAX[spr2] RABIES, PMC) according to a
      standard, post-exposure rabies prophylaxis schedule. Sixty-four healthy adults
      were randomly assigned to four groups of 16 to receive either HRIG/placebo,
      HTRIG/placebo, HRIG/HDCV or HTRIG/HDCV. RIG was administered at the recommended
      dose of 20 IU/kg by three intramuscular (i.m.) injections in the gluteus. HDCV or
      placebo was given on day (D) 0, D3, D7, D14, and D28 into the deltoid by the
      intramuscular (i.m.) route. Any local reaction from D0 to D3 at the immune
      globulin injection site, and any systemic reaction from D0 to D42, were monitored
      by subject diaries. Rabies-neutralizing serum antibody levels were assessed by
      the rapid fluorescent focus inhibition test (RFFIT) before treatment and on D3,
      D7, D14, D28, D35, and D42. No serious adverse reactions and, in particular, no
      allergic-type reactions were reported. The safety profiles of HTRIG and HRIG were
      similar, except that complaints of pain, or tenderness at the injection site were
      half as common in the HTRIG group. Most of the local reactions were mild or
      moderate. After the administration of HTRIG/placebo or HRIG/placebo, 60% of
      subjects had detectable rabies antibodies levels, but by D42 all titres were
      below the seroprotective level (i.e. below 0.5 IU/ml). In the groups HTRIG/HDCV
      and HRIG/HDCV, the antibody titres rose markedly from D7, and reached a maximum
      value of 19 IU/ml (95% CI, 11 to 38 IU/ml) and 31 IU/ml (95% CI, 20 to 48 IU/ml),
      respectively, on day 14. All subjects who received RIG and vaccine maintained a
      protective antibody level from D14 to D42. No significant difference in
      immunogenicity results between these two groups (HTRIG/HDCV and HRIG/HDCV) was
      observed, and no interference of immune globulin with vaccine was reported. The
      safety and immunogenicity profiles of PMC HTRIG appear comparable with the
      current reference product. The heat-treatment step will enhance the safety by
      further reducing the probability of virus transmission through immune globulin
      treatment. The low levels of rabies antibodies obtained by intramuscular
      administration of either PMC HTRIG or of PMC HRIG support the recommendations
      that call for local infiltration of wounds with RIG.

PMID- 9637745
TI  - Studies on the loss of infectivity of live type 3 poliovaccine on storage.
AB  - The Children's Vaccine Initiative established a Product Development Group in 1991
      to help in the development of oral poliovaccines of improved thermostability.
      Under the auspices of this group, the effect of different stabilizers on the loss
      of infectivity of commercial monovalent type 3 live poliovaccine bulks at 37
      degrees C, 42 degrees C and 45 degrees C has been examined. The only effective
      conditions were the maintenance of the pH at 6.5, and the use of deuterium oxide
      at a concentration of 90%. All other additives, including detergents, albumin,
      antiviral compounds, sucrose and magnesium chloride, alone or in combination
      either had no effect or increased the rate of loss of infectivity.

PMID- 9637746
TI  - Stepwise iodination. A general procedure for detoxification of proteins suitable
      for vaccine development and antiserum production.
AB  - By gradual incorporation of stable iodine into toxins and whole venoms it is
      possible to abolish completely the lesion and lethal properties of the native
      components. Allergen extracts can be turned anallergic. Physiological proteins
      with strong biological activity can also be rendered innocuous. Tyrosine and
      histidine are the reactive groups that incorporate the hapten. Within the same
      batch of protein, there is a defined ratio hapten/protein to achieve the desired
      modified properties of the derivative. The iodinating solutions are easily
      prepared, can be accurately standardized and have unlimited shelf lives. The
      derivatives are obtained in a short time. The cost of the entire procedure is
      very low. The method was applied to tityustoxin and whole venom of the scorpion
      Tityus serrulatus; crotoxin and whole venom of Crotalus durissus terrificus; to
      five bothropic venoms; to allergenic extracts of Schistosoma mansoni; to cholera
      and tetanus toxin; and to insulin, kallikrein and tonin. The derivatives obtained
      were stable, did not show any reversion to toxicity, generated antibodies against
      the native antigens and gave active protection when injected into animals. No
      local or systemic side effects were observed, even after prolonged use. The
      injections were also apparently painless. By extensive haptenization self
      proteins can be rendered non-self, able to generate antibodies against both the
      derivative and the native unmodified protein, and iodination was very convenient
      for this purpose. A new schedule for immunization, only feasible with completely
      toxoided venoms is presented. It is based on a clonal expansion induced by a
      small dose, followed by an exponential saturation dose of the same toxoid. The
      attainment of higher levels of antibodies against the native antigen, in the
      generated sera is unmatched by other procedures.

PMID- 9637747
TI  - A simple and rapid method for measuring unconjugated capsular polysaccharide
      (PRP) of Haemophilus influenzae type b in PRP-tetanus toxoid conjugate vaccine.
AB  - The authors developed a simple and rapid method for quantitation of free capsular
      polysaccharide of Haemophilus influenzae type b (polyribosyl ribitol phosphate,
      PRP) in PRP-tetanus toxoid conjugate vaccine based on acid precipitation of
      tetanus toxoid (TT). Acid hydrolysis of PRP during the assay was not detected.
      The conditions used in the assay did not precipitate unconjugated PRP or adipic
      acid dihydrazide derivatized PRP. The method was highly reliable, reproducible
      and sensitive. The accuracy of the assay was confirmed by spiking known amounts
      of unconjugated PRP to PRP-TT conjugate preparations. A PRP-TT preparation,
      incubated at 37 degrees C for 6 months showing most of the PRP as unconjugated
      (87% determined by this method), was not immunogenic in mice for the PRP
      component even after two injections. In contrast, the same preparation held at 4
      degrees C for 20 months, showing 17% unconjugated PRP, induced IgG antibodies to
      PRP which were boosted after second injection. Therefore, this method is very
      useful to evaluate the stability of PRP-TT conjugate vaccine. The assay may be
      useful for characterizing other polysaccharide-protein conjugate vaccines.

PMID- 9637748
TI  - A universal virus inactivant for decontaminating blood and biopharmaceutical
      products.
AB  - Removal of virus infectivity from blood and biopharmaceutical products prepared
      from blood is an issue of considerable importance. For biopharmaceutical
      products, removal can usually be achieved by a series of fractionation steps or
      by inactivation with a suitable reagent. Irrespective of the methods that are
      chosen it is vital that the biological activity of the product is not impaired.
      For blood and unfractionated plasma or serum, the problem is even more
      challenging. Selective inactivation of the genome is the key step in the
      preparation of killed virus vaccines. Viruses belonging to all the recognised
      families can be inactivated by imines. In this paper it is shown that the
      biological properties of several proteins, including the cell growth-promoting
      factors in calf serum, are not impaired using conditions which ensure the
      inactivation of > 10(15) infectious units of poliovirus and foot-and-mouth
      disease virus (FMDV). Also shown is that both viruses can be inactivated by
      imines at 4 degrees C, thus providing a method for removing infectivity from
      protein preparations which are unstable at higher temperatures. The RNA extracted
      from FMDV inactivated at 4 degrees C was not degraded and contained no hidden
      breaks but nevertheless was non-infectious. However, it could be amplified by PCR
      using primers corresponding to the gene coding for a portion of the viral RNA
      polymerase, but not from that coding for VP1, one of the structural proteins,
      showing that alteration of a base or bases had occurred in that region.
      Surprisingly, it could be translated in the rabbit reticulocyte system although
      some of the products were different from those obtained with unmodified RNA.

PMID- 9637749
TI  - Gold, the noble metal and the paradoxes of its toxicology.
AB  - Gold is possibly the most ancient and, in its recent incarnation as a delivery
      vehicle for gene therapy, one of the most modern agents in all of medicine's
      pharmacopoeia. Its administration to humans is both deliberate and inadvertent.
      It is universally recognized as the most inert of metals, yet it can be
      sensitizing. Gold's broadest clinical application (in rheumatoid arthritis)
      derives from a premise that was totally flawed. It is employed clinically to
      effect immune suppression yet it can engender toxicities that stem from
      immunostimulation. To complete this series of paradoxes, the toxicity of gold,
      unlike that of most pharmaceuticals, is, in general, not predictably related to
      the levels it attains within bodily tissues. Accordingly, the pharmacology and
      toxicology of gold is remarkably complex. Recent laboratory discoveries
      concerning gold's metabolism, have emphasized the important metabolic differences
      between its three oxidation states (0, I and III). When placed in the context of
      a wealth of clinical experience, these discoveries provide useful insights into
      its toxicology and shine a revealing light on the mechanisms which account for
      its seemingly paradoxical behaviour.

PMID- 9637750
TI  - A cell-based potency assay for insulin-like growth factor-I.
AB  - The authors developed a cell-based bioassay for determining the potency of
      recombinant human insulin-like growth factor I (IGF-I) using HU-3 human
      megakaryoblastic cell line. Cell proliferation was measured using the alamarBlue
      fluorescence method. The addition of IGF-I resulted in a dose-dependent growth
      response after 48 hours under serum-free conditions. The effective range was 0.1
      25 ng/ml with half-maximal response at approximately 2 ng/ml IGF-I. The assay is
      simple, requiring just three steps, performed in 96-well microtitre plates and is
      able to detect changes in activity of truncated analogues of IGF-I (such as des
      Gly-IGF-I, des-Gly-Pro-IGF-I and des-Gly-Pro-Glu-IGF-I) as well as IGF-I samples
      that had been subjected to proteolytic or disulfide reduction treatments. This
      assay is precise, with interassay variability of less than 10% and accurate, with
      percentage recoveries of nearly 100%. The relative efficacies of other insulin
      related peptides in stimulating cell growth of the cell line were examined. IGF
      II was 5-fold less potent than IGF-I and insulin had little or no proliferative
      activity. In addition, the growth-promoting activity correlated well with IGF-I
      stimulation of glucose consumption in this system. In conclusion, the HU-3 human
      megakaryoblastic cell line constitutes a simple system for measuring the
      biological activity of recombinant IGF-I in quality control set-up. The safety,
      convenience and precision of the assay make it an attractive alternative to
      radioactive and other colorimetric methods.

PMID- 9637751
TI  - EPFA/NIBSC Workshop on Nucleic Acid Amplification Technology (NAT) for the
      detection of blood borne viruses.

PMID- 9637754
TI  - Sublexical Inferences in Beginning Reading: Medial Vowel Digraphs as Functional
      Units of Transfer.
AB  - Two experiments evaluated young children's use of lexical inference. Experiment 1
      compared transfer from shared rimes (e.g., "beak"-"peak"), or heads (e.g., "beak"
      "bean"), under three conditions: (a) when both clue word pronunciation and
      orthography were present at transfer; (b) when only the pronunciation of the clue
      word was given; and (c) when the clue was pretaught. Equivalent transfer occurred
      in both conditions (a and b) where clue word pronunciations were provided at
      transfer, but no transfer was found when the clue word was pretaught (condition
      c). Experiment 2 investigated transfer from three pretaught clue words sharing
      rimes (e.g., "leak"-"peak"), or vowel digraphs (e.g., "leak"-"bean"). Children
      demonstrated lexical transfer under these conditions, but improvements were
      equivalent for vowel and rime analogous words. Results are interpreted in terms
      of models of vowel transfer. Copyright 1998 Academic Press.

PMID- 9637755
TI  - Perceptual constraints on infant memory retrieval.
AB  - In three experiments with 78 3-month-olds, we asked what determines whether or
      not a stimulus will pop out and cue retrieval from long-term memory. All infants
      were trained with mobiles displaying either Qs (feature-present stimuli) or Os
      (feature-absent stimuli) and were tested 24 h later. When the diagonal line of
      the Q bisected its rim, feature-absent stimuli controlled retrieval in tests with
      homogeneous displays, and stimulus novelty controlled retrieval in tests with pop
      out displays. A follow-up experiment revealed that the similarity between Q and O
      determined whether or not Q popped out: When its tail projected externally from
      the rim, Q popped out and cued retrieval, but O did not (search asymmetry). When
      its tail projected internally from the rim, however, 3-month-olds failed to
      discriminate Q from O (the externality effect). These data reveal that target
      distractor similarity constrains whether or not a feature-present stimulus will
      pop out and cue retrieval.

PMID- 9637756
TI  - Intersensory redundancy facilitates learning of arbitrary relations between vowel
      sounds and objects in seven-month-old infants.
AB  - This study investigated 7-month-old infants' ability to relate vowel sounds with
      objects when intersensory redundancy was present versus absent. Infants (N = 48)
      were habituated to two alternating video-films of vowel-object pairs in one of
      three conditions. In the moving-synchronous condition, where redundancy was
      present, the movement of one object was temporally coordinated with the spoken
      vowel /a/ and that of the other with /i/, simulating showing and naming the
      objects to the infant. In the still and in the moving-asynchronous conditions,
      where redundancy was absent, infants saw static objects, and objects moving out
      of synchrony with the vowel sounds, respectively. The results indicated that
      infants detected a mismatch in the vowel-object pairs in the moving-synchronous
      condition but not in the still or the moving-asynchronous condition. These
      findings demonstrate that temporal synchrony between vocalizations and the
      motions of an object facilitates learning of arbitrary speech-object relations,
      an important precursor to the development of lexical comprehension in infancy.

PMID- 9637759
TI  - Differential mononuclear leukocyte attracting chemokine production after
      stimulation with active and inactivated influenza A virus.
AB  - After influenza A virus infection of human monocytes, we found a rapid and marked
      release of the mononuclear cell attracting chemokines MCP-1, MIP-1 alpha, and IP
      10, with corresponding gene expression patterns as determined by Northern blot
      analysis. In striking contrast, the expression and release of the neutrophil
      chemoattractant IL-8 was not inducible. To determine the underlying mechanisms
      responsible for the induction of this differential chemokine pattern, we
      stimulated monocytes with UV- and heat-inactivated (56 degrees C and 100 degrees
      C) influenza A virus. In comparison with fully infectious influenza A, 56 degrees
      C-inactivated virus induced a strong production of MCP-1, MIP-1 alpha, and IP-10,
      while the release of MIP-1 alpha and IP-10 was substantially lower after exposure
      to UV-inactivated virus. No chemokine expression was found after stimulation with
      100 degrees C-inactivated influenza A virus. Our data indicate that, contingent
      upon the chemokine examined, the maximal induction depends on the unrestricted
      infectivity of the virus, the unaltered hemagglutinin molecule, or the intact
      viral RNA. This diversified chemokine production may enable the infected host to
      mount an efficient antiviral response against infective and noninfective virus
      particles.

PMID- 9637760
TI  - Immunological and pathological consequences of mutations in both Fas and Fas
      ligand.
AB  - The lpr mutation in mice results in premature termination of transcription of the
      gene encoding the apoptosis-signaling receptor Fas. As a result, lpr mice develop
      severe lymphoproliferation and lupus-like autoantibodies. Growing evidence
      suggests that the lpr mutation is "leaky" and that low levels of Fas are
      expressed in lpr mice. To determine if Fas expressed in lpr mice is contributing
      to apoptosis we generated a novel strain of mice (B6/lprgld) which is homozygous
      for both the lpr mutation and the gld mutation which encodes nonfunctional Fas
      ligand (FasL) protein. If low levels of Fas in B6/lpr mice contribute to
      apoptosis and lessen the severity of disease, the B6/lprgld mice, which also lack
      functional FasL, would be expected to develop a more severe form of disease than
      B6/lpr mice. Our results revealed no significant increase in either
      lymphoproliferation or autoimmunity in B6/lprgld mice compared to B6/lpr or
      B6/gld mice. Additionally, no increase in surface expression of Fas was detected
      by flow cytometry on B6/lprgld lymphocytes compared to B6/lpr lymphocytes.
      However, histological examination of B6/lprgld liver revealed a marked increase
      in lymphocytic infiltration, compared to livers of B6/lpr and B6/gld mice. Our
      results suggest that, while low levels of Fas in lpr mice may not be contributing
      to amelioration of lymphoproliferation or autoimmunity, they may be partially
      protecting the liver from abnormalities which arise in the absence of Fas
      mediated apoptosis.

PMID- 9637761
TI  - Dendritic cells internalize vaccine adjuvant after intramuscular injection.
AB  - Vaccine adjuvants help antigens elicit rapid, potent, and long-lasting immune
      responses. The lack of understanding of the immunological mechanism of action of
      adjuvants has limited the rational development of vaccines for human use. In
      particular, little is known about how the immune system processes adjuvants. The
      goal of the present study was to determine the fate of the vaccine adjuvant MF59,
      labeled with the fluorescent dye Dil, after injection with fluorescein-labeled
      gD2 antigen from type 2 herpes simplex virus. At 3 h after intramuscular
      injection into BALB/c mice, most of the MF59 was still in the form of
      extracellular droplets in the muscle, but a detectable fraction of the MF59 was
      in cells in the subcapsular sinus of draining inguinal lymph nodes. At 48 h, most
      of the MF59 at the site of injection was inside cells that were immunoreactive
      for the dendritic cell markers DEC-205 and MHC class II molecules, reflecting the
      interaction of MF59 with antigen presenting cells. At this time, intracellular
      MF59 was also abundant in the paracortical (T cell) region of lymph nodes. The
      gD2 antigen was also intracellular in muscle and colocalized MF59 at 48 h, and
      the presence of MF59 increased the amount of intracellular antigen. Similarly,
      serological antibody titers to gD2 were 207-fold higher after two injections when
      MF59 was administered with the antigen. These findings suggest that MF59
      interacts with antigen presenting cells at the site of injection and then moves
      to the draining lymph nodes, where it increases the efficiency of antigen
      presentation to T cells.

PMID- 9637762
TI  - Interaction between human interleukin-2-activated natural killer cells and heat
      killed germ tube forms of Candida albicans.
AB  - Human interleukin-2-activated natural killer (LAK) cells are able to recognize
      and to bind to both live and heat-killed germ tube forms of Candida albicans,
      establishing a wide and intimate contact as revealed by electron microscopic
      observations. Following the interaction, LAK cells are activated: an increased
      expression of some cytokine mRNA (in particular, TNF-alpha, GM-CSF, and IFN
      gamma) has been revealed by RT-PCR and perforin secretion has been suggested by
      immunofluorescence microscopy. Nonetheless, neither morphological damage or
      growth inhibition of fungal target cells have been detected. Instead, evident
      signs of cell damage could be noticed in interacting LAK cells. Moreover, the
      observation by transmission electron microscopy of LAK cell-germ tube conjugates
      revealed the presence of apoptotic cells. The analysis of LAK cell cytotoxic
      activity against DAUDI cells showed that the lymphocytic effector underwent a
      significant reduction in its lytic capability after the interaction with C.
      albicans. The results obtained in this in vitro study seem to indicate that in
      such an interaction LAK cells cannot directly inhibit or kill the fungal pathogen
      by using their lytic machinery but they secrete those cytokines which have
      stimulatory effects on phagocytic cells. The ultimate results are the programmed
      death of LAK cells and the enhancement of the fungicidal activity exerted by
      competent cells.

PMID- 9637763
TI  - Interleukin-12 induces tyrosine phosphorylation of an 85-kDa protein associated
      with the interleukin-12 receptor beta 1 subunit.
AB  - Interleukin-12 (IL12) is a heterodimeric cytokine composed of p35 and p40
      subunits and having multiple immunomodulatory effects on T cells as well as on
      natural killer cells. Two subunits, beta 1 and beta 2, consisting of the
      functional IL12 receptor complex, have been recently identified as members of the
      hemopoietin receptor superfamily, bearing strong homology to gp130. In the
      present study, we attempted to further characterize the biochemical nature of the
      IL12 receptor complex and to delineate IL12-triggered signal transduction
      pathways. To this end, we established a Jurkat transfectant (JIL12R beta 1t)
      highly expressing the recombinant human IL12 receptor beta 1 subunit. Using this
      transfectant, we identified an 85-kDa protein (p85) which is associated with the
      beta 1 subunit and appears to be a cell surface protein, but is distinct from the
      beta 2 subunit (130 kDa). p85 was also detected in PHA-activated T cells.
      Importantly, p85 was rapidly tyrosine phosphorylated upon stimulation of both
      JIL12R beta 1t cells and PHA-activated T cells with IL12. These results suggest
      that p85 is a component of the IL12 receptor complex and may play a significant
      role in mediating IL12-dependent signals.

PMID- 9637764
TI  - Glucocorticoid receptors are differentially expressed in the cells and tissues of
      the immune system.
AB  - Cytosolic glucocorticoid receptor (GR) binding studies on immune tissues
      demonstrate that the thymus exhibits three to four times higher levels of GR
      protein than the spleen. High levels of GR are consistent with the exquisite
      sensitivity of the thymus to glucocorticoid exposure. Nevertheless, whole cell
      binding studies reveal similar levels of GR in immature thymic T lymphocytes and
      more mature, splenic T lymphocytes. Moreover, whole cell binding techniques
      indicate that neutrophils (which represent roughly 30% of splenic leukocytes)
      exhibit higher GR than both T and B lymphocytes, further contradicting results
      from cytosolic binding studies. To address these inconsistencies, GR protein was
      assessed in immune cells and tissues using cytosolic radioligand binding. Western
      blot analysis, and immunocytochemistry. Consistent with previous cytosolic
      receptor binding studies on immune tissue homogenates, thymic T cells were found
      to have higher levels of GR than T cells isolated from the spleen. In addition,
      neutrophils were found to have fewer GR than lymphocytes and monocytes. These
      results indicate a meaningful relationship between receptor expression and known
      sensitivity to glucocorticoids.

PMID- 9637765
TI  - Strength of signal through BCR determines the fate of cycling B cells by
      regulating the expression of the Bcl-2 family of survival proteins.
AB  - Cycling, splenic B cells were recultured with: (1) no stimulant to reflect poorly
      competitive clones; (2) soluble, whole anti-mu to reflect clones that bind
      soluble immune complexes; (3) soluble F(ab')2 anti-mu to reflect clones that bind
      soluble antigen; and (4) immobilized anti-mu to reflect clones that bind antigen
      presented by FDC. All four groups displayed similar levels of the death proteins
      Bax and Bcl-xS. In contrast, cycling B cells restimulated with either soluble
      F(ab')2 or immobilized anti-mu expressed heightened levels of the survival
      protein Bcl-xL, and only cells restimulated with immobilized anti-mu expressed
      the survival protein Bcl-2. Cycling B cells restimulated with either soluble
      F(ab')2 or immobilized anti-mu displayed a selective survival advantage over
      cycling B cells receiving no stimulus or soluble, whole anti-mu by both enhancing
      their responsiveness to CD40 ligand, a Th-cell-derived signal, and increasing the
      period that the cycling B cells remained responsive to this Th-cell-derived
      signal. The Th-cell-derived signal did not appreciably alter cycling B cell
      expression of Bcl-2 family members.

PMID- 9637766
TI  - Human dendritic cells, pulsed with either melanoma tumor cell lysates or the
      gp100 peptide(280-288), induce pairs of T-cell cultures with similar phenotype
      and lytic activity.
AB  - Dendritic cells (DCs) pulsed with unfractionated tumor cell lysates or defined
      tumor peptides provide potent vaccines which elicit strong antitumor immunity. In
      this study, we generated DCs from the 2-h adherent progenitor cells obtained from
      the peripheral blood of melanoma patients. These DCs were able to capture
      biotinylated melanoma tumor cell lysates. We examined the efficacy of immunogens
      composed of DCs loaded either with the melanoma peptide gp100 [amino acids 280
      288 (DC/gp100)] or with lysates from melanoma tumor cells (DC/lysates) in
      inducing cytotoxic T-cells from autologous PBLs of HLA-A2 melanoma patients.
      After four to five weekly stimulations of bulk PBLs with DC/gp100 or DC/lysates,
      the cultures were enriched with CD3+ T-cells and exhibited one of three
      phenotypic and functional patterns: (1) Predominant expression of CD8+ and MHC
      class I-restricted CTLs which displayed strong lytic activity against melanoma
      cells and T2 cells loaded with the gp100 peptide, (2) mixed CD4+/CD8+ phenotype
      and weak lytic activity, or (3) nonlytic and predominantly CD4+ cultures.
      Interestingly, T-cell cultures from each patient exhibited similar phenotypes and
      lytic activities whether the stimulant was DC/gp100 or DC/cell lysates. Our study
      demonstrates that DCs pulsed with soluble melanoma peptides or cell lysates are
      capable of inducing CD8+ CTLs from autologous PBLs of some, but not all, melanoma
      patients. The function and phenotype of the generated T-cell cultures are
      governed by DCs since both antigens (the gp100 peptide and melanoma lysates),
      when presented by a given DC preparation, induced similar T-cell cultures. In
      summary, it may be difficult to predict the nature of the cellular responses
      elicited by DC/tumor antigen vaccines from patient to patient.

PMID- 9637767
TI  - Identification of a lectin that induces cell death in developing chicken B cells.
AB  - The bursa of Fabricius is required for the development of a diverse B cell
      repertoire in chickens. Bursal B cells are dependent on survival signals within
      the bursa and their removal from the bursa results in death by apoptosis. To find
      molecules that regulate B cell survival, a panel of mAb and lectins was screened
      for the ability to either accelerate or prevent B cell death in culture. The
      fucose-specific lectin Aleuria aurantia agglutinin (AAA) rapidly rendered B cells
      permeable to propidium iodide. Incubation with the lectin also accelerated the
      appearance of internucleosomal DNA fragmentation and nuclear condensation,
      characteristics of apoptotic cell death. On Western blots the lectin detects a
      single protein band of approximately 48-50 kDa molecular weight. AAA detects
      fucose in an alpha 1-6 linkage and the restriction of this fucose linkage to a
      single protein suggests that it may be functionally important in the regulation
      of cell survival.

PMID- 9637769
TI  - The LCC15-MB human breast cancer cell line expresses osteopontin and exhibits an
      invasive and metastatic phenotype.
AB  - We have characterized the LCC15-MB cell line which was recently derived from a
      breast carcinoma metastasis resected from the femur of a 29-year-old woman. LCC15
      MB cells are vimentin (VIM) positive, exhibit a stellate morphology in routine
      cell culture, and form penetrating colonies when embedded in three-dimensional
      gels of Matrigel or fibrillar collagen. They show high levels of activity in the
      Boyden chamber chemomigration and chemoinvasion assays, and like other invasive
      human breast cancer (HBC) cell lines, LCC15-MB cells activate matrix
      metalloproteinase-2 in response to treatment with concanavalin A. In addition,
      these cells are tumorigenic when implanted subcutaneously in nude mice and
      recolonize bone after arterial injection. Interestingly, both the primary lesion
      and the bone metastasis from which LCC15-MB were derived, as well as the
      resultant cell line, abundantly express the bone matrix protein osteopontin
      (OPN). OPN is also expressed by the highly metastatic MDA-MB-435 cells, but not
      other invasive or noninvasive HBC cell lines. Expression of OPN is retained in
      the subcutaneous xenograft and intraosseous metastases of LCC15-MB as detected by
      immunohistochemistry. Both VIM and OPN expression have been associated with
      breast cancer invasion and metastasis, and their expression by the LCC15-MB cell
      line is consistent with its derivation from a highly aggressive breast cancer.
      These cells provide a useful model for studying molecular mechanisms important
      for breast cancer metastasis to bone and, in particular, the implication(s) of
      OPN and VIM expression in this process.

PMID- 9637770
TI  - Regulation of protrusion shape and adhesion to the substratum during chemotactic
      responses of mammalian carcinoma cells.
AB  - We report here the first direct observation of chemotaxis to EGF by rat mammary
      carcinoma cells. When exposed to a gradient of EGF diffusing from a micropipette,
      MTLn3 cells displayed typical ameboid chemotaxis, extending a lamellipod-like
      protrusion and moving toward the pipette. Using a homogeneous upshift in EGF to
      model stimulated lamellipod extension (J. E. Segall et al., 1996, Clin. Exp.
      Metastasis 14, 61-72), we analyzed the relationship between adhesion and
      chemoattractant-stimulated protrusion. Exposure to EGF led to a rapid remodeling
      of the adhesive contacts on adherent cells, in synchrony with extension of a flat
      lamellipod over the substratum. EGF-stimulated lamellipods still extended in the
      presence of adhesion-blocking peptides or over nonadhesive surfaces. They were,
      however, slightly shorter and retracted rapidly under those conditions. The major
      protrusive structure observed on well-spread, adherent cells, after EGF
      stimulation was a flat broad lamellipod, whether or not in contact with the
      substratum, while cells in suspension showed transient protrusive activity over
      the entire cell surface. We conclude that the initial adhesive status of the cell
      conditions the shape of the outcoming protrusion. Altogether our results suggest
      that, although adhesive contacts are not necessary for lamellipod extension, they
      play a role in stabilizing the protrusion as well as in the control of its final
      shape and amplitude.

PMID- 9637771
TI  - The Clk2 and Clk3 dual-specificity protein kinases regulate the intranuclear
      distribution of SR proteins and influence pre-mRNA splicing.
AB  - The three members of the Clk family of kinases (Clk1, 2, and 3) have been shown
      to undergo conserved alternative splicing to generate catalytically active (Clk)
      and inactive (ClkT) isoforms. The prototype, murine Clk1 (mClk1), is a nuclear
      dual-specificity kinase that can interact with, and cause the nuclear
      redistribution of, SR proteins. In this study, we demonstrate that the human Clk2
      and Clk3 (hClk2 and 3) are also found within the nucleus and display dual
      specificity kinase activity. The truncated isoforms, hClk2(T) and hClk3(T),
      colocalize with SR proteins in nuclear speckles. We also show catalytically
      active hClk2 and hClk3 cause the redistribution of SR proteins and can regulate
      the alternative splicing of a model precursor mRNA substrate in vivo.

PMID- 9637772
TI  - Cytochemical detection of a senescence-associated beta-galactosidase in
      endothelial and smooth muscle cells from human and rabbit blood vessels.
AB  - A beta-galactosidase activity has recently been used as a histochemical marker of
      replicative senescence in human fibroblasts and keratinocytes. To establish
      whether this marker could be used to detect senescence of vascular cells, we have
      investigated its presence in cultures of serially passaged human umbilical vein
      endothelial cells and rabbit aortic smooth muscle cells. beta-Galactosidase
      activity was detected by light microscopy using the chromogenic substrate 5-bromo
      4-chloro-3-indolyl beta-d-galactopyranoside. In endothelial cell cultures,
      lysosomal beta-galactosidase activity, which is detected at pH 4.0, was present
      in all cells regardless of their replicative age. In contrast, senescence
      associated beta-galactosidase activity, which is detected at pH 6.0, was absent
      in the majority of cells in early passage cultures (<15 cumulative population
      doublings), but was present in a large proportion of cells (up to 62%) in late
      passage cultures (>30 cumulative population doublings); in intermediate passage
      cultures (15-30 cumulative population doublings) it was found in fewer than 15%
      of the cells. The increase in the percentage of senescence-associated beta
      galactosidase-positive cells correlated with a decrease in the cell density at
      confluence and with a marked increase in cell size. Counterstaining with an
      antibody directed against the endothelial cell marker CD31 showed that senescent
      cells retained the expression of this antigen. Senescence-associated beta
      galactosidase was also detected in serially passaged, but not in primary explant
      cultures of rabbit aortic vascular smooth muscle cells. The presence of
      senescence-associated beta-galactosidase in cultured vascular smooth muscle cells
      and endothelial cells suggests that this marker could be used to study the role
      of cellular senescence in vascular disease.

PMID- 9637773
TI  - Age changes in stem cells of murine small intestinal crypts.
AB  - Cell senescence is seen in many types of differentiated cells but age changes in
      stem cells have not previously been clearly demonstrated. Changes in stem cells
      may be of great importance for the ageing process, because any decline with age
      in the numbers and functional integrity of stem cells can lead to progressive
      deterioration of function and of proliferative homeostasis in tissues. Stem cells
      of the murine small intestine provide an excellent model system because these
      cells occupy a well-defined position near the base of the crypts of Lieberkuhn.
      We examined mice aged between 5 and 32 months and found age-related alterations
      in the histology of the small intestine and in the apoptotic response of stem
      cells to low-dose irradiation. Apoptosis in the crypts is concentrated around the
      stem cell position and can be markedly elevated by exposure to radiation or
      cytotoxic agents, suggesting that "suicide" of damaged stem cells may be an
      important system for long-term tissue maintenance. Animals aged 5, 15, 18, and 29
      months were exposed to either 1 or 8 Gy gamma irradiation. A twofold increase in
      the level of apoptosis was seen following 1 Gy gamma irradiation in the 29-month
      old animals, compared to the young and middle-age groups. After 8 Gy irradiation
      the level of apoptosis in all age groups was high and the age effect less
      pronounced. The data suggest that stem cells do undergo some functional
      alteration with age.

PMID- 9637774
TI  - Hypophosphorylation of the RB protein in S and G2 as well as G1 during growth
      arrest.
AB  - The RB tumor suppressor protein is a cell cycle regulator, where
      hypophosphorylated RB is associated with G1/0 arrest and its cyclin-dependent
      phosphorylation in G1 allows progression from G1 to S. The present report shows
      that in human leukemia cells induced to undergo growth arrest with sodium
      butyrate or DMSO, hypophosphorylation of the RB protein is not G1 restricted and
      also occurs in S and G2/M cells as well as in G1 cells when growth is inhibited.
      While all of the RB protein in G1/0 cells is hypophosphorylated, residual cells
      in S and G2 have significant detectable amounts of hypophosphorylated RB as well
      as still hyperphosphorylated RB protein. Thus RB hypophosphorylation can be
      induced in S and G2 as well as the G1 phase. The results show that growth
      retardation in other than the G1 phase is associated with occurrence of
      hypophosphorylated RB. RB may thus have a broader capability to inhibit
      proliferation than just in G1.

PMID- 9637775
TI  - Characterization of topotecan-mediated redistribution of DNA topoisomerase I by
      digital imaging microscopy.
AB  - Topographical image measures have been used to characterize the subnuclear
      distribution of DNA topoisomerase I in human tumor cell lines. This topographical
      analysis allowed a mathematical description of staining patterns to be produced
      that did not depend on subjective grading. The redistribution of topoisomerase I
      in response to increasing concentrations of topotecan was then monitored by this
      method. The cell lines were stained for topoisomerase I by indirect
      immunofluorescence methods. Digital imaging microscopy and image analysis were
      used to extract the nucleus from each cell, and nine parameters describing the
      topography of the distribution of topoisomerase I within the nucleus were
      computed for each. Use of multivariate analysis of variance enabled this nine
      parameter set to be reduced to a single canonical variable, representing 60-90%
      of the observed internuclear variance. Plotting the canonical variable vs drug
      concentration resulted in dose-response curves that could be fitted well by a
      simple Emax model. From these curve fits, EC50 and Emax values for drug-induced
      redistribution of topoisomerase I were determined. Our results indicate that
      neither the maximum extent of topoisomerase I redistribution (Emax) nor the EC50
      for drug-induced redistribution correlated well with the growth inhibition
      produced by continuous exposure to topotecan in these cell lines. However, the
      EC50 determined for the 1-h high-concentration exposure did reflect the growth
      inhibition produced in cells exposed to the drug for 1 h. The methodology
      described may also be generally applied to any antigen of interest.

PMID- 9637776
TI  - Inhibition of Cdk2 activation by selected tyrphostins causes cell cycle arrest at
      late G1 and S phase.
AB  - We have previously reported that certain tyrphostins which block EGF-R
      phosphorylation in cell-free systems fail to do so in intact cells. Nevertheless,
      we found that this family of tyrphostins inhibits both EGF- and calf serum
      induced cell growth and DNA synthesis [Osherov, N.A., Gazit, C., Gilon, and
      Levitzki, A. (1993). Selective inhibition of the EGF and HER2/Neu receptors by
      Tyrphostins. J. Biol. Chem. 268, 11134-11142.] Now we show that these tyrphostins
      exert their inhibitory activity even when added at a time when the cells have
      already passed their restriction point and receptor activation is no longer
      necessary. AG555 and AG556 arrest 85% of the cells at late G1, whereas AG490 and
      AG494 cause cells to arrest at late G1 and during S phase. No arrest occurs
      during G2 or M phase. Further analysis revealed that these tyrphostins act by
      inhibiting the activation of the enzyme Cdk2 without affecting its levels or its
      intrinsic kinase activity. Furthermore, they do not alter the association of Cdk2
      to cyclin E or cyclin A or to the inhibitory proteins p21 and p27. These
      compounds also have no effect on the activating phosphorylation of Cdk2 by Cdk2
      activating kinase (CAK) and no effect on the catalytic domain of cdc25
      phosphatase. These compounds lead to the accumulation of phosphorylated Cdk2 on
      tyrosine 15 which is most probably the cause for its inhibition leading to cell
      cycle arrest at G1/S. A structure-activity relationship study defines a very
      precise pharmacophore, suggesting a unique molecular target not yet identified
      and which is most probably involved in the regulation of the tyrosine
      phosphorylated state of Cdk2. These compounds represent a new class of cell
      proliferation blockers whose target is Cdk2 activation.

PMID- 9637777
TI  - Increased rate of HIV-1 entry and its cytopathic effect in CD4+/CXCR4+ T cells
      expressing relatively high levels of CD26.
AB  - The role of the T-cell activation antigen CD26 was evaluated in viral entry and
      infection of CD4(+)/CXCR4(+) cells by the lymphotropic HIV-1 Lai isolate. For
      this purpose, CEM T cells, which are permissive to HIV infection and express low
      levels of CD26, were used to establish by transfection four groups of cell clones
      expressing either low, high, and very high levels of CD26, or expressing the anti
      sense RNA of CD26. Entry was monitored by the detection of proviral DNA synthesis
      and the kinetics of virus production, whereas the cytopathic effect was
      demonstrated by the occurrence of apoptosis. HIV entry and infection were
      consistently accelerated by at least 24 to 48 h in clones expressing high levels
      of CD26 compared to the parental cells or to the clones expressing low levels of
      CD26. Interestingly, infection of clones expressing very high levels of CD26 was
      not accelerated and showed a kinetics of infection similar to that of low CD26
      expressing clones. Moreover, HIV infection was significantly reduced in the
      clones expressing CD26 anti-sense RNA. In the different clones, apoptosis was
      dependent on the severity of virus infection and occurred after the accumulation
      of HIV envelope glycoproteins. Our results demonstrate that with equivalently
      expressed levels of CD4 and CXCR4 in cell lines established from CEM cells,
      relatively high levels of CD26 contribute to an increased rate of HIV entry,
      infection, and apoptosis. Furthermore, they point out that overexpression of CD26
      in a given cell line may lead to a negative effect on HIV infection.
      Consequently, CD26 appears to regulate HIV entry and apoptosis, processes which
      are critical for viral pathogenesis.

PMID- 9637778
TI  - PKN interacts with a paraneoplastic cerebellar degeneration-associated antigen,
      which is a potential transcription factor.
AB  - PKN is a fatty acid-activated serine/threonine protein kinase, having a catalytic
      domain homologous to protein kinase C family. PKN has been recently reported to
      interact with a small GTP-binding protein Rho and cytoskeletal proteins such as
      neurofilament and alpha-actinin. To identify the new components of the PKN
      signaling pathway, the yeast two-hybrid system was employed. Using the amino
      terminal regulatory domain of PKN as a bait, cDNA encoding a neural antigen
      PCD17, which is recognized by characteristic antibodies of patients with
      paraneoplastic cerebellar degeneration, was isolated from a human brain cDNA
      library. The interaction between PKN and PCD17 was also determined by the in
      vitro binding analysis. PCD17 was coimmunoprecipitated with PKN from the lysate
      of COS7 cells transfected with both expression constructs for PKN and the amino
      terminal region of PCD17. PCD17 was phosphorylated by PKN, and the extent of this
      phosphorylation was enhanced by addition of 40 microM arachidonic acid. The amino
      terminal region of PCD17 could form a homodimer in vitro, and PCD17 fused to the
      Gal4 DNA binding domain showed the transcriptional transactivation of the
      chloramphenicol acetyltransferase reporter gene linked to 5 Gal4 binding sites
      and minimal promoter in rat C6 glioma cells. These results suggest the
      participation of PCD17 in gene expression and lead to a clue for elucidating the
      PKN signaling pathway from the cytosol to the nucleus.

PMID- 9637779
TI  - Apoptotic changes preceding necrosis in lipopolysaccharide-treated macrophages in
      the presence of cycloheximide.
AB  - Apoptotic changes occurred specifically in a macrophage-like cell line, J774.1,
      treated with lipopolysaccharide (LPS) and cycloheximide (CHX) prior to the
      release of lactate dehydrogenase (LDH). The addition of 100 ng/ml LPS and 10
      microg/ml CHX induced both the formation of DNA nicks and elevation of caspase-3
      like activity (DEVDase) after 75 min, and then the cleavage of poly(ADP-ribose)
      polymerase (PARP) into 28-kDa fragments, formation of apoptotic bodies, and DNA
      ladder formation. These apoptotic changes were reversible until 60 min, however,
      later than 75 min after LPS and CHX addition, the apoptosis proceeded normally
      even on extensive washing of the macrophages, which removed the LPS and CHX.
      These results suggest that there is a "point of no return" in the apoptotic
      processes in macrophages induced by LPS and CHX and that DNA nicks and activation
      of DEVDase are critical for these processes.

PMID- 9637780
TI  - Mitochondrial membrane potential and DNA stainability in human sperm cells: a
      flow cytometry analysis with implications for male infertility.
AB  - Sperm cells from control donors of proven fertility and men from barren couples
      were studied by conventional procedures, i.e., light microscopy as well as flow
      cytometry. Light microscopy analysis of semen included the measurement of
      spermatozoa concentration, morphology, and motility. All the men from barren
      couples were asthenozoospermic at the conventional analysis of semen samples.
      Flow cytometry was applied to study two important parameters of sperm cells:
      mitochondrial membrane potential (MMP) assessed by the cationic dye JC-1 and DNA
      stainability with propidium iodide (PI). JC-1 staining was more reliable than the
      classical procedure used for this purpose, i.e., rhodamine 123 (Rh123) staining,
      and allowed us to show a positive correlation between MMP and spermatozoa
      motility. Regarding DNA analysis, a higher relative percentage of immature
      spermatozoa, showing a high accessibility of DNA to the intercalating PI
      fluorochrome, was found in men from barren couples compared to donors of proven
      fertility. The relative percentage of immature spermatozoa was significantly
      higher in semen from oligoasthenozoospermic subjects. Moreover, a positive
      correlation was found between immature spermatozoa, as evaluated by PI staining,
      and cells with depolarized mitochondria, as evaluated by JC-1 staining,
      suggesting that spermatozoa defective for nuclear maturity could be functionally
      defective cells. No correlation between immature spermatozoa determined by FCM
      and immature spermatozoa determined by light microscopy was found, suggesting
      that these two techniques assess sperm cell maturity at different levels.

PMID- 9637781
TI  - The human myoepithelial cell exerts antiproliferative effects on breast carcinoma
      cells characterized by p21WAF1/CIP1 induction, G2/M arrest, and apoptosis.
AB  - Ductal carcinoma in situ of the breast (DCIS) is surrounded by a layer of
      myoepithelial cells. Our previous studies have suggested that these myoepithelial
      cells exert paracrine tumor-suppressive effects on invasion of breast carcinoma
      cells. Conditioned medium (CM), concentrated 10-100x of HMS-1, HMS-3, and HMS-4,
      human myoepithelial cell lines, block Matrigel invasion of a series of carcinoma
      cell lines. Immunoprecipitation of maspin, a recently described serpin, from
      these CM abolishes this anti-invasive effect. Both CM and maspin
      immunoprecipitated CM, however, exert equal antiproliferative effects on a series
      of ER+ and ER- cell lines including MCF-7, T47D, MDA-MB-231, and MDA-MB-468.
      These antiproliferative effects are characterized by induction of a G2/M arrest,
      a twofold increase in p21(WAF1/CIP1) transcription and expression, and a
      threefold increase in apoptosis in the breast carcinoma lines examined. The
      antiproliferative effects mediated by myoepithelial cell CM do not manifest
      themselves in an autocrine manner, are not mediated by TGF-beta1, nor involve ER-
      or p53-dependent pathways. Neither the antiproliferative nor the anti-invasive
      effects of myoepithelial cell CM is observed with nonmyoepithelial cell CM. The
      in vitro observations of our present study may have relevance in explaining the
      increased degree of apoptosis exhibited by DCIS cells in vivo. Our findings
      illustrate another way myoepithelial cells function as natural paracrine tumor
      suppressors.

PMID- 9637782
TI  - The expression of heat shock protein 70 decreases with cellular senescence in
      vitro and in cells derived from young and old human subjects.
AB  - Because heat shock proteins have been shown to play a critical role in protecting
      cells from hyperthermia and other types of stresses, it was of interest to
      determine what effect cellular senescence in vitro and cells cultured in vitro
      from young and old human donors have on the ability of cells to regulate the
      expression of heat shock protein 70 (hsp70), the most prominent and most
      evolutionary conserved of the heat shock proteins. The ability of early and late
      passage IMR-90 lung fibroblasts and epidermal melanocytes and skin fibroblasts
      obtained from young and old human donors to express hsp70 was determined after a
      brief heat shock. We found that the levels of hsp70 protein and mRNA were lower
      in late passage cells and cells from old donors than in early passage cells and
      cells from young donors. The binding activity of the heat shock transcription
      factor HSF1, as measured by a gel shift assay, was significantly higher in early
      passage cells and cells from young donors in comparison to late passage cells and
      cells from old donors. In addition, the levels of HSF1 decreased significantly in
      late passage cells and cells from old donors in comparison to early passage cells
      and cells from young donors. Thus, our study demonstrates that the induction of
      hsp70 by hyperthermia in fibroblasts is significantly lower in late passage
      fibroblasts and in fibroblasts from old donors. In addition, our study shows that
      the decline in hsp70 expression during cellular senescence in vitro and in cells
      derived from old human subjects is paralleled by a decrease in the levels of
      HSF1.

PMID- 9637783
TI  - Regulation of vascular endothelial growth factor receptor-2 (Flk-1) expression in
      vascular endothelial cells.
AB  - We have previously reported the existence of a synergistic interaction between
      vascular endothelial growth factor (VEGF) and basic fibroblast growth factor
      (bFGF) in the induction of angiogenesis in vitro. Here we demonstrate that bFGF
      increases VEGF receptor-2 (VEGFR-2/Flk-1) expression: mRNA levels were increased
      by 4.5- to 8.0-fold and total protein by 2.0- to 3.5-fold, in bovine
      microvascular endothelial (BME), aortic endothelial (BAE), and transformed fetal
      aortic (GM7373) endothelial cells. VEGF itself did not affect VEGFR-2 expression,
      and neither bFGF nor VEGF altered expression of FGF receptor-1. We also show that
      synergism occurs at the level of proliferation when this is measured in a three
      dimensional but not in a conventional two-dimensional assay. Differences in the
      level of VEGFR-2 expression were also observed when cells were grown on or within
      collagen gels under different conditions: mRNA levels were lowest under sparse
      conditions, increased 20- to 26-fold at confluence, and increased even further
      (57-fold) when cells were cultured in suspension in three-dimensional collagen
      gels. Finally, a synergistic increase was seen in the level of expression of
      urokinase and urokinase receptor mRNAs when cells were exposed to bFGF and VEGF
      for 4 days. These findings demonstrate that the level of VEGFR-2 expression can
      be modulated by environmental factors including cytokines and the geometry of the
      culture conditions and provide some insight into the mechanisms of synergism
      between bFGF and VEGF in the induction of angiogenesis in vitro.

PMID- 9637784
TI  - PK11195, a ligand of the mitochondrial benzodiazepine receptor, facilitates the
      induction of apoptosis and reverses Bcl-2-mediated cytoprotection.
AB  - One critical step of the apoptotic process is the opening of the mitochondrial
      permeability transition (PT) pore leading to the disruption of mitochondrial
      membrane integrity and to the dissipation of the inner transmembrane proton
      gradient (Delta Psim). The mitochondrial PT pore is a polyprotein structure which
      is inhibited by the apoptosis-inhibitory oncoprotein Bcl-2 and which is closely
      associated with the mitochondrial benzodiazepine receptor (mBzR). Here we show
      that PK11195, a prototypic ligand of the 18-kDa mBzR, facilitates the induction
      of Delta Psim disruption and subsequent apoptosis by a number of different
      agents,including agonists of the glucocorticoid receptor,chemotherapeutic agents
      (etoposide, doxorubicin),gamma irradiation, and the proapoptotic second messenger
      ceramide. Whereas PK11195 itself has no cytotoxic effect, it enhances apoptosis
      induction by these agents. This effect is not observed for benzodiazepine
      diazepam, whose binding site in the mBzR differs from PK11195. PK11195 partially
      reverses Bcl-2 mediated inhibition of apoptosis in two different cell lines.
      Thus, transfection-enforced Bcl-2 overexpression confers protection against
      glucocorticoids and chemotherapeutic agents, and this protection is largely
      reversed by the addition of PK11195. This effect is observed at the level of
      Delta Psim dissipation as well as at the level of nuclear apoptosis. To gain
      insights into the site of action of PK11195, we performed experiments on isolated
      organelles. PK11195 reverses the Bcl-2-mediated mitochondrial retention of
      apoptogenic factors which cause isolated nuclei to undergo apoptosis in a cell
      free system. Mitochondria from control cells, but not mitochondria from Bcl-2
      overexpressing cells, readily release such apoptogenic factors in response to
      atractyloside, a ligand of the adenine nucleotide translocator. However, control
      and Bcl-2-overexpressing mitochondria respond equally well to a combination of
      atractyloside and PK11195. Altogether, these findings indicate that PK11195
      abolishes apoptosis inhibition by Bcl-2 via a direct effect on mitochondria.
      Moreover, they suggest a novel strategy for enhancing the susceptibility of cells
      to apoptosis induction and, concomitantly, for reversing Bcl-2-mediated
      cytoprotection.

PMID- 9637785
TI  - The regulation of cyclin D1 expression in senescent human fibroblasts.
AB  - To clarify the molecular mechanisms of cyclin D1 expression during in vitro
      cellular aging, we investigated the binding of nuclear protein factors to the
      cyclin D1 gene promoter domain in young and senescent normal human fibroblasts.
      The cyclin D1 promoter binding activities of nuclear protein factors from young
      and senescent cells were examined by the gel mobility shift assay. Our findings
      revealed that (i) the binding of a specific nuclear factor to the enhancer
      element was very weak in senescent cells; (ii) the binding of a specific nuclear
      factor to the CRE, which is independent of cell growth, was unchanged between
      young and senescent cells; (iii) nuclear factors from senescent cells did not
      bind to the presumptive silencer element; (iv) the binding of specific factors to
      the Inr (transcription initiation region) and E2F increased with growth
      stimulation in young cells and was weakly detectable in senescent cells; and (v)
      the binding of Sp1 to its promoter element occurred only in senescent cells. The
      analysis of the silencer element by the gel mobility shift assay revealed that
      the essential sequence required for binding of specific factors to the silencer
      element was TTTAAT. The molecular weight of the binding factor to the silencer
      element was determined to be approximately 35 kDa by the Southwestern blotting
      and UV cross-linking assay. Thus, we postulated that the observed increase of
      cyclin D1 expression during cellular aging is due to an increase in the binding
      activity of specific nuclear protein factors to an enhancer element, Sp1, and a
      decrease in binding to a silencer element in senescent cells.

PMID- 9637786
TI  - Phenobarbital suppresses growth and accelerates restoration of differentiation
      markers of primary culture rat hepatocytes in the chemically defined hepatocyte
      growth medium containing hepatocyte growth factor and epidermal growth factor.
AB  - Phenobarbital (PB), a liver-tumor promoter, at a concentration of 3 mM
      dramatically inhibited the growth of adult rat hepatocytes in the chemically
      defined medium, HGM, with added hepatocyte growth factor (HGF) and epidermal
      growth factor (EGF). In concurrence with these findings, PB down-regulated
      expression of the HGF receptor (c-met) and suppressed production of the autocrine
      growth factor transforming growth factor-alpha (TGF-alpha). Furthermore, PB down
      regulated expression of transcription factors associated with proliferation such
      as AP1 and NF-kappaB. In the presence of PB, hepatocytes remained morphologically
      differentiated and restoration of the expression of mature hepatocyte markers,
      such as albumin and cytochrome P450s (1A, 2B1/2, and 2E1), was accelerated after
      an initial phase of growth. Additionally, PB strongly suppressed expression of
      the mRNA for alpha-fetoprotein, a protein primarily expressed by fetal liver, and
      the accelerative effect of PB on restoration of mature hepatocyte markers showed
      a correlation with the up-regulation of the hepatocyte-enriched transcription
      factors HNF3 and HNF4. When the effects of PB on various extracellular matrix
      proteins were examined, the data indicated that PB specifically suppressed
      laminin and fibronectin production by hepatocytes, suggesting an important role
      for these proteins in growing hepatocyte cultures.

PMID- 9637787
TI  - Nucleotide excision repair is not required for the antiapoptotic function of
      insulin-like growth factor 1.
AB  - The expression of ERCC1, a member of the nucleotide excision repair (NER) family,
      is enhanced in cells transfected with insulin-like growth factor 1 (IGF-1)
      receptors. Of interest, an excellent concordance between ERCC1 expression and NER
      mediated cell survival has been demonstrated. The two aims of the present study
      were to determine the signaling pathways used by IGF-1 to confer protection
      against apoptotic cell death in Chinese hamster ovary (CHO) cells and to assess
      the role of NER in this IGF-1 action. Experiments with pharmacological inhibitors
      indicated that phosphatidylinositol 3-kinase (PI 3-kinase) but not mitogen
      activated protein kinase (ERK1/ERK2) mediates IGF-1 antiapoptotic activity. Using
      two series of CHO cells that have altered expression of ERCC1 or XPB/ERCC3, we
      examined IGF-1's ability to delay apoptotic death and reduction of mitochondrial
      oxidative function mediated by growth factor withdrawal. IGF-1 effectively
      blocked apoptosis, concomitant with increased MTT activity, in a pair of CHO cell
      lines expressing inactive ERCC1 (43-3B cells) and the transfected line of the
      mutant carrying the expressed human ERCC1 gene (83-G5 cells). Similarly, repair
      deficient UV24 cells, which lack XPB/ERCC3, and their parental line AA8 were also
      responsive to the IGF-1's antiapoptotic capacity. In the presence of IGF-1, these
      cell lines became resistant to the cleavage of poly(ADP-ribose) polymerase, a key
      player in DNA damage recognition and DNA repair. These results suggest that PI 3
      kinase activation plays a determinant role in the antiapoptotic function of IGF
      1, but that functional NER does not play a critical part in mediating this IGF-1
      response.

PMID- 9637788
TI  - Adjacent carboxyterminal tyrosine phosphorylation events identify functionally
      distinct ErbB2 receptor subsets: implications for molecular diagnostics.
AB  - Site-directed mutagenesis can define the effects of altering one or more amino
      acids within a protein, but this technique may lack sensitivity when used to
      characterize proteins which differ conformationally or posttranslationally at
      multiple sites. A novel alternative approach involves the direct characterization
      of wild-type protein isoforms identified by site-specific immunodetection. To
      this end we have developed antibodies which recognize ErbB2 subsets characterized
      by adjacent tyrosine phosphorylation events (Y1222 and Y1248) in the C-terminal
      tail of the oncoprotein. Here we use these phosphoantibodies to demonstrate the
      existence of tyrosine-phosphorylated ErbB2 subsets which differ in their patterns
      of heterooligomer formation, in vitro autophosphorylation, and recruitment of SH2
      containing substrates. Furthermore, Y1222 and/or Y1248 phosphoantibody
      immunoreactivity is readily detectable in ErbB2-overexpressing human breast
      tumors, in which context these phosphorylation events exhibit significant
      discordance. These data confirm the value of site-specific immunodetection as a
      strategy for characterizing phosphoprotein function in vitro and in vivo and
      suggest that multisite phosphotyping of human tumors may contribute novel
      clinicopathologic insights into the significance of the ErbB2 overexpression
      phenotype.

PMID- 9637789
TI  - In vivo effects of hepatocyte growth factor/scatter factor on mouse mammary gland
      development.
AB  - We have recently demonstrated the regulated expression of HGF/SF and its receptor
      (c-met) during mouse mammary gland development together with the mitogenic,
      motogenic and morphogenic effects of exogenous HGF/SF on primary mammary
      epithelial cells in culture. This study was undertaken to analyze the influence
      of HGF/SF on reconstituted mouse mammary gland development in vivo. Here we
      report that overexpression of HGF/SF induces a range of alterations in the
      architecture of virgin mouse mammary gland. These include an enhancement of
      ductal end bud (mammary gland morphoregulatory control point) size and numbers
      and hyperplastic branching morphogenesis. These data are the first demonstration
      of the effects of HGF/SF on mammary epithelium in vivo.

PMID- 9637791
TI  - A severely affected male born into a Rett syndrome kindred supports X-linked
      inheritance and allows extension of the exclusion map.

PMID- 9637792
TI  - The Environmental Genome Project: functional analysis of polymorphisms.
AB  - The ultimate goal of the Environmental Genome Project is the improvement of human
      health on the basis of information about the variations in certain genes. The
      first phase of the project will involve the selection of the human genes and
      characterization of the alleles occurring in the American population. However,
      intelligent use of this information will require analysis of the relevance of the
      allelic differences. Epidemiology alone will not solve the problem, and
      mechanistic studies will be required. Factors to be considered in the design of
      functional analyses are considered in this commentary.

PMID- 9637793
TI  - A case of a laboratory animal feed with high estrogenic activity and its impact
      on in vivo responses to exogenously administered estrogens.
AB  - We recently noted that immature rats failed to exhibit a normal uterine response
      to exogenously administered estradiol as assessed by both biochemical (induction
      of gene expression) and morphological (altered uterine and vaginal histology and
      size) end points. An initial analysis suggested that this was due to a high
      degree of estrogenization from a dietary source which was producing a near
      maximal uterotrophic response prior to hormone treatment. Subsequent chemical
      analysis indicated that the feed in question contained high amounts of two well
      known phytoestrogens, genistein (210 mg/kg) and daidzen (14 mg/kg), and the lot
      of feed in question produced a large uterotrophic effect when fed to immature
      ovariectomized rats. These findings illustrate that, despite increased awareness
      of phytoestrogens, some batches of animal feed contain very high amounts of
      estrogenic components which have marked effects on in vivo end points of hormone
      action. These observations have important implications for both basic research
      and screening methods that utilize in vivo approaches.

PMID- 9637795
TI  - A specific spectrum of p53 mutations in lung cancer from smokers: review of
      mutations compiled in the IARC p53 database.
AB  - Mutations in the p53 gene are common in lung cancer. Using data from the the
      International Agency for Research on Cancer p53 mutation database (R1), we have
      analyzed the distribution and nature of p53 mutations in 876 lung tumors
      described in the literature. These analyses confirm that G to T transitions are
      the predominant type of p53 mutation in lung cancer from smokers. The most
      frequently mutated codons include 157, 158, 179, 248, 249, and 273, and several
      of them (157, 248, and 273) have been shown to correspond to sites of in vitro
      DNA adduct formation by metabolites of polycyclic aromatic hydrocarbons (PAHs)
      such as benzo(a)pyrene. Furthermore, most of the base changes at codons 248, 249,
      and 273 in lung cancer differ from those commonly observed at these codons in
      other cancers reported in the database. Thus, lung cancer from smokers shows a
      distinct, unique p53 mutation spectrum that is not observed in lung cancer from
      nonsmokers. These results further strengthen the association between active
      smoking, exposure to PAHs, and lung cancer. They also indicate that a different
      pattern of mutations occurs in nonsmokers, and this observation may help to
      identify other agents causally involved in lung cancer in nonsmokers.

PMID- 9637794
TI  - Oxidative stress in toxicology: established mammalian and emerging piscine model
      systems.
AB  - Interest in the toxicological aspects of oxidative stress has grown in recent
      years, and research has become increasingly focused on the mechanistic aspects of
      oxidative damage and cellular responses in biological systems. Toxic consequences
      of oxidative stress at the subcellular level include lipid peroxidation and
      oxidative damage to DNA and proteins. These effects are often used as end points
      in the study of oxidative stress. Typically, mammalian species have been used as
      models to study oxidative stress and to elucidate the mechanisms underlying
      cellular damage and response, largely because of the interest in human health
      issues surrounding oxidative stress. However, it is becoming apparent that
      oxidative stress also affects aquatic organisms exposed to environmental
      pollutants. Research in fish has demonstrated that mammalian and piscine systems
      exhibit similar toxicological and adaptive responses to oxidative stress. This
      suggests that piscine models, in addition to traditional mammalian models, may be
      useful for further understanding the mechanisms underlying the oxidative stress
      response.

PMID- 9637796
TI  - A physiologically based pharmacokinetic model for 2,4-toluenediamine leached from
      polyurethane foam-covered breast implants.
AB  - Physiologically based pharmacokinetic (PBPK) modeling was used to assess the low
      dose exposure of patients to the carcinogen 2, 4-toluenediamine (2,4-TDA)
      released from the degradation of the polyester urethane foam (PU) used in Meme
      silicone breast implants. The tissues are represented as five compartments:
      liver, kidney, gastrointestinal tract, slowly perfused tissues (e.g., fat), and
      richly perfused tissues (e.g., muscle). The PBPK model was fitted to the plasma
      and urine concentrations of 2,4-TDA and its metabolite 4-AAT (4-N-acetyl-2-amino
      toluene) in rats given low doses of 2, 4-TDA intravenously and subcutaneously.
      The rat model was extrapolated to simulate oral and implant routes in rats. After
      adjusting for human physiological parameters, the model was then used to predict
      the bioavailability of 2,4-TDA released from a typical 4.87-g polyester urethane
      foam implant found in a patient who weighed 58 kg with the Meme and had the
      breast implant for 10 years. A quantitative risk assessment for 2,4-TDA was
      performed and the polyester urethane foam did present an unreasonable risk to
      health for the patient.

PMID- 9637797
TI  - A morbidity study of former pentachlorophenol-production workers.
AB  - Pentachlorophenol (PCP) is a pesticide that was once widely used for wood
      preservation. Commercial PCP contained impurities including higher chlorinated
      dibenzo-p-dioxins (CDDs) and chlorinated dibenzofurans (CDFs). We investigated
      the effects of occupational exposure to PCP and its CDD and CDF contaminants on
      the skin, liver, porphyrin metabolism, and central and peripheral nervous
      systems. In 1986 we conducted a medical survey of 366 workers who had been
      engaged in the production of PCP at a single plant between 1938 and 1978. The
      referent group consisted of 303 workers from the same plant who were not exposed
      to these or related compounds. Exposure was determined from computerized
      personnel records. The medical survey included an administered questionnaire,
      medical record review, physical examination by dermatologists, internists, and
      neurologists, and analysis of 24-hr urine for quantitative porphyrins among other
      tests. In this paper we present the results of analyses of the general health,
      chloracne, and porphyrin metabolism end points. The general health status of PCP
      workers was similar to unexposed workers, but 17.8% of PCP workers had evidence
      of current or past chloracne. PCP workers with chloracne had significantly higher
      mean urinary excretion of coproporphyrins (117. 0 vs. 90.6 microg/24 hr) than
      unexposed workers after controlling for potential confounders. Workers with
      chloracne who had worked with both PCP and polychlorinated biphenyls had
      significantly higher mean urinary excretions of hepta-, penta-, and
      coproporphyrins than unexposed workers. We conclude that occupational exposure to
      PCP is associated with chloracne and biochemical abnormalities which may persist
      years after exposure.

PMID- 9637798
TI  - Microcystic cyanobacteria causes mitochondrial membrane potential alteration and
      reactive oxygen species formation in primary cultured rat hepatocytes.
AB  - Cyanobacteria contamination of water has become a growing public health problem
      worldwide. Microcystis aeruginosa is one of the most common toxic cyanobacteria.
      It is capable of producing microcystins, a group of cyclic heptapeptide compounds
      with potent hepatotoxicity and tumor promotion activity. The present study
      investigated the effect of microcystic cyanobacteria on primary cultured rat
      hepatocytes by examining mitochondrial membrane potential (MMP) changes and
      intracellular reactive oxygen species (ROS) formation in cells treated with
      lyophilized freshwater microcystic cyanobacteria extract (MCE). Rhodamine 123 (Rh
      123) was used as a fluorescent probe for changes in mitochondrial fluorescence
      intensity. The mitochondrial Rh-123 fluorescence intensity in MCE-treated
      hepatocytes, examined using a laser confocal microscope, responded in a dose- and
      time-dependent manner. The results thus indicate that the alteration of MMP might
      be an important event in the hepatotoxicity caused by cyanobacteria. Moreover,
      the parallel increase of ROS formation detected using another fluorescent probe,
      2',7'-dichlorofluorescin diacetate also suggests the involvement of oxidative
      stress in the hepatotoxicity caused by cyanobacteria. The fact that MMP changes
      precede other cytotoxic parameters such as nuclear staining by propidium iodide
      and cell morphological changes suggests that mitochondrial damage is closely
      associated with MCE-induced cell injury in cultured rat hepatocytes.

PMID- 9637799
TI  - Factors associated with self-reported, pesticide-related visits to health care
      providers in the agricultural health study.
AB  - To investigate factors associated with pesticide-related visits to health care
      providers (i.e., doctor or hospital visits), responses to self-administered
      questionnaires received from 35,879 licensed restricted-use pesticide applicators
      participating in the Agricultural Health Study were analyzed. (In Iowa,
      applicators are actually certified, whereas in North Carolina they are licensed;
      for ease of reference, the term license will be used for both states in this
      paper.) The cohort reported a total of more than 10.9 million pesticide
      application days. These applications were associated with one or more pesticide
      related health care visits by 2,214 applicators (7.0% of the applicator cohort
      for whom health care visit data were available). The odds of a pesticide-related
      health care visit were increased for commercial applicators compared to private
      applicators [odds ratio (OR = 1.77; 95% confidence interval (CI), 1.52-2.06) and
      for applicators who used insecticides 70 times or more in their lifetime compared
      to those who used insecticides less frequently (OR = 1.43; CI, 1.26-1.63). After
      adjusting for the number of applications in a logistic regression model,
      significantly higher odds of health care visits were observed among North
      Carolina applicators compared to Iowa applicators (OR = 1.35; CI, 1.17-1.52),
      among applicators who mixed their own pesticides (OR = 1.65; CI, 1. 22-2.23), and
      among applicators who personally repaired their pesticide application equipment
      at least once per year (OR = 1.12; CI, 1.06-1.25). Significantly lower odds were
      found among female versus male applicators (OR = 0.68; CI, 0.46-0.99) and among
      applicators who graduated from high school versus those who did not (OR = 0.82;
      CI, 0.71-0.94 for high school graduates and OR = 0.79; CI, 0.68-0.91 for those
      with at least some college). Several methods of pesticide application to crops,
      seed, or stored grain were also associated with significantly elevated odds
      ratios of health care visits. These observations suggest that several steps can
      be taken to reduce the number of health care visits resulting from occupational
      exposure to pesticides. The implications of this pattern of pesticide-related
      health care visits may have etiologic implications for cancer and other chronic
      diseases.

PMID- 9637801
TI  - Toxic tides.

PMID- 9637800
TI  - Aromatic hydrocarbon receptor polymorphism: development of new methods to
      correlate genotype with phenotype.
AB  - Differential CYP1A1 inducibility, reflecting variations in aromatic hydrocarbon
      receptor (AHR) affinity among inbred mouse strains, is an important determinant
      of environmental toxicity. We took advantage of the Ahr polymorphism in C57BL/6
      and DBA/2 mice to develop an oligonucleotide-hybridization screening approach for
      the rapid identification of DNA sequence differences between Ahr alleles.
      Oligonucleotides containing single-base changes at polymorphic sites were
      immobilized on a solid support and hybridized with C57BL/6 or DBA/2 AHR cDNA
      radiolabeled probes. The observed hybridization patterns demonstrate that this
      approach can be used to detect nucleotide differences in the Ahr coding region
      with very high accuracy. In parallel experiments, we used a yeast two-hybrid
      system to assess phenotypic differences in AHR function. AHR activation, as
      measured by beta-galactosidase reporter activity in Saccharomyces cerevisiae
      strain SFY526, was determined following treatment with varying doses of the AHR
      ligand beta-naphthoflavone (BNF). We found that the C57BL/6 AHR has about a 15
      fold higher affinity for BNF than the DBA/2 AHR, in much better agreement with
      results reported for whole-animal studies than the values observed by in vitro
      ligand-binding assays. Using C57BL/6 and DBA/2 AHR chimeric proteins, we also
      confirmed the previously reported observation that an A375V change is principally
      responsible for the high- to low-affinity AHR phenotype. There has been no
      straightforward method to reliably and reproducibly phenotype large numbers of
      humans for CYP1A1 inducibility or AHR affinity. Screening human AHR cDNAs by
      oligonucleotide-hybridization and yeast two-hybrid methodologies will be
      invaluable for the rapid and unequivocal determination of changes in DNA sequence
      and receptor-ligand affinities associated with human AHR polymorphisms.

PMID- 9637802
TI  - Cleaner water: it's elementary.

PMID- 9637803
TI  - Regulation of the extracellular ligand binding activity of integrins.
AB  - Integrins are a large heterodimeric family of cell surface adhesion receptors
      that bind extracellular matrix and cell surface ligands. The extracellular ligand
      binding activity of integrins is a dynamic and highly regulated event involving
      the induction of conformational changes within the integrin structure. The
      adhesive properties of integrins can be controlled by altering the activation
      state of the integrin, either through conformational change or receptor
      clustering, using mechanisms that are regulated by intracellular proteins. In
      this review, we will discuss what is currently known about integrin structure and
      the ligand binding sites present within the receptor. In addition, the mechanisms
      by which the ligand binding event is regulated through conformational change will
      be addressed, and the potential role of intracellular cytoplasmic proteins will
      be discussed.

PMID- 9637804
TI  - An outbreak of multidrug-resistant pneumococcal pneumonia and bacteremia among
      unvaccinated nursing home residents.
AB  - BACKGROUND: Outbreaks of pneumococcal disease are uncommon and have occurred
      mainly in institutional settings. Epidemic, invasive, drug-resistant pneumococcal
      disease has not been seen among adults in the United States. In February 1996,
      there was an outbreak of multidrug-resistant pneumococcal pneumonia among the
      residents of a nursing home in rural Oklahoma. METHODS: We obtained
      nasopharyngeal swabs for culture from residents and employees. Streptococcus
      pneumoniae isolates were serotyped and compared by pulsed-field gel
      electrophoresis. A retrospective cohort study was conducted to identify factors
      associated with colonization and disease. RESULTS: Pneumonia developed in 11 of
      84 residents (13 percent), 3 of whom died. Multidrug-resistant S. pneumoniae,
      serotype 23F, was isolated from blood and sputum from 7 of the 11 residents with
      pneumonia (64 percent) and from nasopharygeal specimens from 17 of the 74
      residents tested (23 percent) and 2 of the 69 employees tested (3 percent). All
      the serotype 23F isolates were identical according to pulsed-field gel
      electrophoresis. Recent use of antibiotics was associated with both colonization
      (relative risk, 2.3; 95 percent confidence interval, 1.3 to 4.2) and disease
      (relative risk, 3.6; 95 percent confidence interval, 1.2 to 10.8). Only three
      residents (4 percent) had undergone pneumococcal vaccination. After residents
      received pneumococcal vaccine and prophylactic antibiotics, there were no
      additional cases of pneumonia, and the rates of carriage decreased substantially.
      CONCLUSIONS: In this outbreak a single pneumococcal strain was disseminated among
      the residents and employees of a nursing home. The high prevalence of
      colonization with a virulent organism in an unvaccinated population contributed
      to the high attack rate. Clusters of pneumococcal disease may be underrecognized
      in nursing homes, and wider use of pneumococcal vaccine is important to prevent
      institutional outbreaks of drug-resistant S. pneumoniae infection.

PMID- 9637805
TI  - A comparison of rectal diazepam gel and placebo for acute repetitive seizures.
AB  - BACKGROUND: Acute repetitive seizures are readily recognizable episodes involving
      increased seizure frequency. Urgent treatment is often required. Rectal diazepam
      gel is a promising therapy. METHODS: We conducted a randomized, double-blind,
      parallel-group, placebo-controlled study of home-based treatment for acute
      repetitive seizures. Patients were randomly assigned to receive either rectal
      diazepam gel, at a dosage varying from 0.2 to 0.5 mg per kilogram of body weight
      on the basis of age, or placebo. Children received one dose at the onset of acute
      repetitive seizures and a second dose four hours later. Adults received three
      doses -- one dose at onset, and two more doses 4 and 12 hours after onset.
      Treatment was administered by a care giver, such as a parent, who had received
      special training. The number of seizures after the first dose was counted for 12
      hours in children and for 24 hours in adults. RESULTS: Of 125 study patients (64
      assigned to diazepam and 61 to placebo) with a history of acute repetitive
      seizures, 91 (47 children and 44 adults) were treated for an exacerbation of
      seizures during the study period. Diazepam treatment was superior to placebo with
      regard to the outcome variables related to efficacy: reduced seizure frequency
      (P<0.001) and improved global assessment of treatment outcome by the care giver
      (frequency and severity of seizures and drug toxicity) (P<0.001). Post hoc
      analysis showed diazepam to be superior to placebo in reducing seizure frequency
      in both children (P<0.001) and adults (P=0.02), but only in children was it
      superior with regard to improvement in global outcome (P<0.001). The time to the
      first recurrence of seizures after initial treatment was longer for the patients
      receiving diazepam (P<0.001). Thirty-five patients reported at least one adverse
      effect of treatment; somnolence was the most frequent. Respiratory depression was
      not reported. CONCLUSIONS: Rectal diazepam gel, administered at home by trained
      care givers, is an effective and well-tolerated treatment for acute repetitive
      seizures.

PMID- 9637806
TI  - Effects of metformin on spontaneous and clomiphene-induced ovulation in the
      polycystic ovary syndrome.
AB  - BACKGROUND: Obese women with the polycystic ovary syndrome are relatively
      unresponsive to the induction of ovulation by clomiphene. We hypothesized that
      reducing insulin secretion by administering metformin would increase the
      ovulatory response to clomiphene. METHODS: We performed oral glucose-tolerance
      tests before and after the administration of 500 mg of metformin or placebo three
      times daily for 35 days in 61 obese women with the polycystic ovary syndrome.
      Women who did not ovulate spontaneously were then given 50 mg of clomiphene daily
      for five days while continuing to take metformin or placebo. Serum progesterone
      was measured on days 14, 28, 35, 44, and 53, and ovulation was presumed to have
      occurred if the concentration exceeded 8 ng per milliliter (26 nmol per liter) on
      any of these days. RESULTS: Twenty-one women in the metformin group and 25 women
      in the placebo group were given clomiphene because they did not ovulate
      spontaneously during the first phase of the study. Among the 21 women given
      metformin plus clomiphene, the mean (+/-SE) area under the serum insulin curve
      after oral glucose administration decreased from 6745+/-2021 to 3479+/-455 microU
      per milliliter per minute (40.5+/-12.1 to 20.9+/-2.7 nmol per liter per minute,
      P=0.03), but it did not change significantly in the 25 women given placebo plus
      clomiphene. Nineteen of the 21 women (90 percent) who received metformin plus
      clomiphene ovulated (mean peak serum progesterone concentration, 23.8+/-3.4 ng
      per milliliter [7.6+/-10.9 nmol per liter]). Two of the 25 women (8 percent) who
      received placebo plus clomiphene ovulated (P<0.001). Overall, 31 of the 35 women
      (89 percent) treated with metformin ovulated spontaneously or in response to
      clomiphene, as compared with 3 of the 26 women (12 percent) treated with placebo.
      CONCLUSIONS: The ovulatory response to clomiphene can be increased in obese women
      with the polycystic ovary syndrome by decreasing insulin secretion with
      metformin.

PMID- 9637807
TI  - Use of misoprostol during pregnancy and Mobius' syndrome in infants.
AB  - BACKGROUND: Patients with upper gastrointestinal ulceration may be treated with
      misoprostol, but it is not recommended for pregnant women because it may
      stimulate uterine contractions and cause vaginal bleeding and miscarriage. Recent
      data from Brazil, where misoprostol is used orally and vaginally as an
      abortifacient, have suggested a relation between the use of misoprostol by women
      in an unsuccessful attempt to terminate pregnancy and Mobius' syndrome
      (congenital facial paralysis) in their infants. METHODS: We compared the
      frequency of misoprostol use during the first trimester by mothers of infants in
      whom Mobius' syndrome was diagnosed and mothers of infants with neural-tube
      defects in Brazil. All diagnoses in infants were made between January 16, 1990,
      and May 31, 1996, by clinical geneticists at seven hospitals who also interviewed
      the mothers and recorded information about the administration of misoprostol,
      among other data. RESULTS: We identified 96 infants with Mobius' syndrome and
      matched them with 96 infants with neural-tube defects. The mean age at the time
      of the diagnosis of Mobius' syndrome was 16 months (range, 0.5 to 78), and the
      diagnosis of neural-tube defects was made within 1 week of birth in most cases.
      Among the mothers of the 96 infants with Mobius' syndrome, 47 (49 percent) had
      used misoprostol in the first trimester of pregnancy, as compared with 3 (3
      percent) of the mothers of the 96 infants with neural-tube defects (odds ratio,
      29.7; 95 percent confidence interval, 11.6 to 76.0). Twenty of the mothers of the
      infants with Mobius' syndrome had taken misoprostol only orally (odds ratio,
      38.8; 95 percent confidence interval, 9.5 to 159.4), 20 had taken misoprostol
      both orally and vaginally, 3 had taken the drug vaginally, and 4 did not report
      how they took the drug. CONCLUSIONS: Attempted abortion with misoprostol is
      associated with an increased risk of Mobius' syndrome in infants.

PMID- 9637808
TI  - Images in clinical medicine. Tuberous sclerosis.

PMID- 9637809
TI  - Images in clinical medicine. Ash-leaf spots in tuberous sclerosis.

PMID- 9637810
TI  - The reproducibility of a method to identify the overuse and underuse of medical
      procedures.
AB  - BACKGROUND: To assess the overuse and underuse of medical procedures, various
      methods have been developed, but their reproducibility has not been evaluated.
      This study estimates the reproducibility of one commonly used method. METHODS: We
      performed a parallel, three-way replication of the RAND-University of California
      at Los Angeles appropriateness method as applied to two medical procedures,
      coronary revascularization and hysterectomy. Three nine-member multidisciplinary
      panels of experts were composed for each procedure by stratified random sampling
      from a list of experts nominated by the relevant specialty societies. Each panel
      independently rated the same set of clinical scenarios in terms of the
      appropriateness of the relevant procedure on a risk-benefit scale ranging from 1
      to 9. Final ratings were used to classify the procedure in each scenario as
      necessary or not necessary (to evaluate underuse) and inappropriate or not
      inappropriate (to evaluate overuse). Reproducibility was measured by overall
      agreement and by the kappa statistic. The criteria for underuse and overuse
      derived from these ratings were then applied to real populations of patients who
      had undergone coronary revascularization or hysterectomy. RESULTS: The rates of
      agreement among the three coronary-revascularization panels were 95, 94, and 96
      percent for inappropriate-use scenarios and 93, 92, and 92 percent for necessary
      use scenarios. Agreement among the three hysterectomy panels was 88, 70, and 74
      percent for inappropriate-use scenarios. Scenarios involving necessary use of
      hysterectomy were not assessed. The three-way kappa statistic to detect overuse
      was 0.52 for coronary revascularization and 0.51 for hysterectomy. The three-way
      kappa statistic to detect underuse of coronary revascularization was 0.83.
      Application of individual panels' criteria to real populations of patients
      resulted in a 100 percent variation in the proportion of cases classified as
      inappropriate and a 20 percent variation in the proportion of cases classified as
      necessary. CONCLUSIONS: The appropriateness method is far from perfect.
      Appropriateness criteria may be useful in comparing levels of appropriate
      procedures among populations but should not by themselves be used to direct care
      for individual patients.

PMID- 9637811
TI  - Rating the appropriateness of coronary angiography--do practicing physicians
      agree with an expert panel and with each other?
AB  - BACKGROUND: Evaluations of the appropriateness of medical care are important to
      monitor the quality of care and to contain costs and enhance safety by reducing
      inappropriate care. Experts' views are usually incorporated into evaluations of
      appropriateness. However, practicing physicians may not concur with these views,
      and physicians' clinical backgrounds may influence their beliefs. METHODS: We
      asked 1058 internists, family practitioners, and cardiologists in California,
      Florida, New York, Pennsylvania, and Texas to rate the appropriateness of
      coronary angiography after acute myocardial infarction for 20 common indications.
      Nine clinical experts also rated these indications using an established consensus
      method. RESULTS: For 17 of the 20 indications, median ratings of surveyed
      physicians and the expert panel agreed within 1 unit on a 9-unit scale. Patients'
      older age had a negative effect on ratings by the expert panel but not on ratings
      by surveyed physicians. In multivariable analyses of surveyed physicians,
      cardiologists rated angiography as significantly more appropriate than did
      primary care physicians for complicated indications, and for uncomplicated
      indications cardiologists who performed invasive procedures gave higher
      appropriateness ratings for angiography than did cardiologists who did not
      perform such procedures and primary care physicians. For uncomplicated
      indications, physicians from hospitals providing coronary angioplasty and bypass
      surgery rated angiography as more appropriate than physicians from other
      hospitals. Physicians from New York and those employed by health maintenance
      organizations rated angiography as less appropriate than other physicians.
      CONCLUSIONS: Surveyed physicians agreed with clinical experts about the
      appropriateness of coronary angiography after myocardial infarction for most
      indications, indicating that well-designed expert panels can closely reflect the
      views of practicing physicians. Variations in beliefs among practicing physicians
      suggest that evaluations of medical practice should incorporate the views of a
      range of relevant types of physicians.

PMID- 9637813
TI  - Pneumococcal outbreaks in nursing homes.

PMID- 9637814
TI  - Gaining a perspective on childhood seizures.

PMID- 9637815
TI  - What is appropriate care?

PMID- 9637816
TI  - Differential expression of Galalpha1,3Gal epitope in polymeric and monomeric IgM
      secreted by mouse myeloma cells deficient in alpha2, 6-sialyltransferase.
AB  - IgM are glycoproteins secreted by plasma cells as (mu2L2)5+J or (mu2L2)6
      polymers. In most species, mu- and J-chains bear five and one N -glycans,
      respectively. Here we compare the terminal glycosylation patterns of 4-hydroxy-3
      nitrophenylacetyl (NP)-specific IgM secreted by transfectants of the J558L mouse
      myeloma deficient in the alpha2,6 sialyltransferase [alpha2,6ST(N)] or by a
      hybridoma expressing this enzyme (B1.8 cells). The absence of alpha2,6
      sialylation results in an increased addition of alpha1, 3-galactosyl residues to
      mu- and J-chain N-glycans. Since alpha1, 3-galactosyltransferase (alpha1,3Gal-T)
      is similarly expressed in the two cell lines, these results indicate that a
      competition reaction occurs in vivo between alpha2,6ST(N) and alpha1,3Gal-T. In
      the alpha2,6ST(N) deficient transfectants, mu-chains lacking the C-subterminal
      Cys575 residue, which are secreted mainly in the form of mu2L2 monomers, are more
      efficiently capped by alpha1, 3-galactosyl residues, confirming that
      polymerization significantly reduces the accessibility of mu-chain glycans to the
      Golgi processing enzymes involved in the biogenesis of antennary sugars.
      Functional assays indicate that IgM sialylation affects antigen-binding and
      complement-dependent hemolysis of haptenated red blood cells.

PMID- 9637817
TI  - [Laboratory media for the cultivation of tubercle bacillus].
AB  - A variety of different media for the cultivation of mycobacteria have been
      described but a few of them are in use today. Those currently used can be
      characterized by three basic types. The first is egg-based media represented by
      Ogawa and Lowenstein-Jensen. The second type is agar-based media; the most common
      one are Middlebrook 7H10 and 7H11. The third type is liquid media such as
      Middlebrook 7H9. Several weeks of incubation may be required for the isolation of
      M. tuberculosis on solid media. Substantial improvement in the time to detection
      and the recovery rate was realized by using broth-based culture system such as
      the BACTEC 460TB, Septi-Chek AFB, MGIT and BACTEC 9000. In the BACTEC 460TB
      system, the mycobacteria is detected radiometrically. The processed specimen is
      added to a modified 7H9 medium (BACTEC 12B) containing 14C-labeled palmitic acid
      and an antibiotic complex, PANTA. Mycobacterial growth can be ascertained by the
      liberation of 14CO2 and detected by BACTEC 460TB instrument. The Septi-Chek AFB
      is a biphasic medium which combines broth and solid media. The liquid medium is a
      modified Middlebrook 7H9 in a carbon-dioxide-enriched culture bottle. After
      inoculation of the sample, the bottle is capped with a slide consisting of three
      solid media; a non-selective Middlebrook 7H11 agar, an egg-based medium, and
      chocolate agar. A novel system is the MGIT, which is a nonradiometric broth
      method for the detection of mycobacteria from clinical specimens. The MGIT
      consists of a modified Middlebrook 7H9 broth and a sensor embedded in silicone on
      the bottom of a tube. The appearance of orange-colored fluorescence in the sensor
      when excited indicates the growth of mycobacteria. MB Redox is a modified, serum
      supplemented Kirchner medium containing p-indonitrotetrazolium violet (INT) as an
      indicator of microbial growth. The INT is reduced by the redox system of the
      mycobacteria to deep violet-colored formazan. This substance is water insoluble
      and is reduced to the cell surface, by which bacterial clamps can be easily
      detected by their violet color. At present, the egg-based media are the first
      choice for the culture of clinical samples. However, there are advantages to each
      type of medium and not all strains of mycobacteria can be recovered on a single
      medium. Therefore, it is recommended that one representative of each type of
      medium be used for primary isolation; one example in Japan may be Ogawa egg
      medium in combination with Middlebrook 7H11 and MGIT.

PMID- 9637818
TI  - [Development of the intratracheal infection model of experimental murine
      mycobacteriosis: comparison with the intravenous infection model].
AB  - An intratracheal infection method of experimental murine mycobacteriosis was
      developed for an in vivo study of antimycobacterial agents. Two models of
      intratracheal (IT) and intravenous (i.v.) routes of infection with mycobacteria
      of the same inoculum dose were compared in terms of the mean survival days of
      mice or bacterial loads in organs during the course of infection. IT model with
      either of M. bovis Ravenel, M. tuberculosis Kurono, M. tuberculosis H37Rv or M.
      intracellular N-256 exhibited a much more distinct lung-specific infection than
      i.v. model with the same dose of respective mycobacterial strains. The
      intratracheal infection method presented in this report does not require any
      special equipment and is a much safer method for the researcher than airborne
      infection. In this model, following slight anesthetizing of mice, bacillary
      suspension was injected quantitatively into lungs through the mouth and trachea
      by using a specially modified needle set with a short fine polyethylene tube.
      This IT model may be useful not only for the in vivo assessment of anti
      mycobacterial agents but also for the comparison of virulence among various
      mycobacterial strains.

PMID- 9637819
TI  - [Diagnostic usefulness of the tuberculin reaction by PPD-B in Mycobacterium avium
      complex disease].
AB  - This study was carried out to clarify the diagnostic usefulness of the skin tests
      of purified protein derivatives from M. intracellulare (PPD-B) and M.
      tuberculosis (PPDs). Study subjects consisted of 41 patients with primary
      infection type of M. avium complex (MAC) disease, 36 patients with pulmonary
      tuberculosis (TB) and 29 patients with other bacterial respiratory infections
      including COPD (OB). The patients were sorted out to middle (50-69 y.o.) and old
      (70-89 y.o.) age groups of each disease. The size of skin redness elicited 48
      hours after the PPD-B and PPDs intradermal injections were compared among them.
      The results were as follows. 1) Both PPD-B and PPDs skin reactions were larger in
      the middle age group than in the old one for each disease. 2) In PPDs skin tests,
      the reaction of TB group was the largest among the three diseases. In PPD-B skin
      tests, that of MAC was the largest. 3) In TB group, PPDs skin reaction was
      significantly larger than that of PPD-B, while in MAC and OB groups there was no
      significant difference between the skin reactions of PPDs and PPD-B. 4) Defining
      significant positive reaction to PPD-B as PPD-B skin reaction exceeding 10 mm and
      larger than that of PPDs skin reaction, the rate of significant positive reaction
      to PPD-B was significantly higher in MAC than TB in both age groups. These
      results showed that the simultaneous skin tests of PPD-B and PPDs were a useful
      aid in the diagnosis of MAC infection disease when mycobacterial infection
      diseases were clinically suspected by bacteriological or chest radiographic
      examinations.

PMID- 9637820
TI  - [A preventable case who died of miliary tuberculosis after receiving contact
      examination].
AB  - A 30-year-old-man was admitted to our hospital because of headache and fever. His
      consciousness on admission was clouding. Sputum examination was positive for acid
      fast bacilli which later identified as Mycobacterium tuberculosis. Chest-X-ray
      and computed tomogram on admission showed multiple cavitary lesions on bilateral
      upper lung fields and bilateral diffuse nodular shadow. He was diagnosed as
      miliary tuberculosis with tuberculous meningitis. His mother admitted because of
      pulmonary tuberculosis four months ago, and her sputum examination was smear
      positive for acid fast bacilli, Gaffky 4, and she complained of cough for 6
      months before admission. Because of this situation, he rapidly underwent the
      contact examination with chest X-ray, but not examined by tuberculin skin test
      because he was 30-year-old. As then chest X-ray was normal, he was not indicated
      of chemoprophylaxis, and he died of miliary tuberculosis and tuberculous
      meningitis 4 months after the contact examination.

PMID- 9637821
TI  - [Establishment of new diagnostic technique and its clinical application for
      nontuberculous mycobacterial infections].
AB  - The clinical futures of 52 patients with pulmonary Mycobacterium avium complex
      infection (MAC group), 7 M. kansasii infection (MK group), and 5 M. chelonae
      infection (MC group) were studied. Aged female was dominant in MAC and MC group,
      while middleaged man was dominant in MK group. Although body mass index (BMI) was
      the lowest in MAC group, there was no difference between the groups in clinical
      sign, symptom, and laboratory data. Type III radiological finding was dominant in
      MAC group, while type II in MK and MC groups. Bacteriological eradication rate of
      causative organisms was 86% in MK group, 54% in MAC group, and 40% in MC group.
      However, the relation between clinical efficacy of chemotherapy, BMI, serum
      protein level, and cavity formation in chest radiogram was not observed. MAC was
      detected in clinical samples such as sputum, bronchial washing fluid, and gastric
      juice with 5 to 10% in frequency by Amplicor, one of commercially available PCR
      detection kits for mycobacteria. Furthermore 60% to 80% of the MAC positive cases
      were diagnosed and treated as nontuberculous mycobacteriosis. Although MAC is
      occasionally exist in oral cavity or clinical environment, the positive result of
      genetic diagnostic method such as Amplicor should be carefully considered.

PMID- 9637822
TI  - [The short-term effects of multidrug chemotherapy for pulmonary Mycobacterium
      avium-intracellulare complex (MAC) infection].
AB  - In performing MAC chemotherapy, we are faced with the following two problems:
      first, unlike for Mycobacterium tuberculosis, we have neither any suitable
      bacteriocidal drugs nor bacteriocidal regimens for MAC treatment; secondly, in
      case of MAC, unlike in the case of Mycobacterium tuberculosis, in vitro
      sensitivity does not correlate with in vivo sensitivity. For these reasons, we
      find difficulty in planning a rational protocol for MAC treatment, and thus
      depend on previous experiences of other physicians in MAC chemotherapy. Here, we
      have tried to evaluate such previous experiences objectively, and studied
      retrospectively the effects of previous combination chemotherapy cases of
      pulmonary MAC infections at National Tokyo Hospital. We selected 170 cases which
      had received the same chemotherapy continuously over a period of six months.
      Concentration of bacilli cultured, 8 weeks in Ogawa solid egg containing medium
      was translated semi-quantitatively to colony forming units (CFU) according to the
      Japanese guideline for acid fast bacilli test. Having set a mean CFU of 3 times
      sputum culture before treatment as 100%, we calculated a six month sequential
      bacillary response to a regimen and plotted the bacillary response curves. The
      response curve of the total 170 MAC treatment cases exhibits a minimum point of
      42.9% at 2 months, and subsequently rises to 71.1% after six months compared to
      the state before treatment. The response curves of various regimens of multidrug
      chemotherapy indicate that combinations of more than 3 drugs including
      aminoglycoside and clarithromycin are most effective. However, although some
      effectiveness is indicated, neither the present drugs nor regimens are capable to
      achieve a bacteriocidal effect in MAC treatment.

PMID- 9637823
TI  - [Geographical distribution of Mycobacterium avium complex in environment and
      serovars of Mycobacterium avium complex isolates from patients with and without
      AIDS].
AB  - Mycobacterium avium complex (MAC) organisms have been isolated from water and
      soil. It is now generally accepted that environmental sources, especially natural
      waters, are the reservoirs for most human infections caused by MAC. Previously,
      we reported that M. avium and M. intracellular were distributed predominantly in
      the eastern and western part of Japan, respectively. To clarify the factor(s) of
      the difference, the following experiment was undertaken. MAC was isolated from
      soil samples collected in Tokai, Kinki and Chugoku districts, by the method of
      Ichiyama et al. MAC isolates were identified by AccuProbe Confirmation and
      Identification tests, together with some conventional tests. Seven (11.7%) of 60
      isolates were identified as M. avium, twenty (33%) as M. intracellulaer and 33
      (55%) as MAC-like organisms. Therefore, it was not found that the difference in
      the geographical distribution between soil MAC and disease-associated MAC. MAC
      like strains possess MAC-specific alpha antigen, and biological and biochemical
      features of MAC. They reacted with the AccuProbe MAC but not with the AccuProbe
      M. avium and M. intracellulare. Sequencing analysis of 16s RNA gene implies that
      MAC-like strains show an intermediate sequence pattern of M. avium and M.
      intracellulare. HPLC patterns of these strains were compatible with those of MAC.
      It is known that the major serovars of MAC isolates from patients with or without
      AIDS are different. Serological aspects in this respect are not yet elucidated
      well in Japan. The major serovars of MAC from patients with AIDS are 4 and 8 in
      the USA and Australia, 6 and 4 in Sweden, and 8/21 and 8 in Germany. On the other
      hand, the major serovars of MAC from patients without AIDS are 8 and 16 (15) in
      the USA and 6 and 1 in Sweden. According to out recent study the major serovars
      of MAC from non-AIDS patients are 1 and 8 in the eastern part and 16 and 14 in
      the western part of Japan. In the present study, 38 MAC isolates from sputum,
      stool and blood and AIDS patients were identified. All of the isolates were
      identified as M. avium. Serovars of 15 strains were 4 (4 strains), 8 (3 strains),
      9 (3 strains), 3 (2 strains), Darkin (2 strains) and 1 (1 strain). Therefore, it
      seems that the major serovars of the Japanese MAC strains from AIDS patients are
      similar to those of the American MAC strains from such patients.

PMID- 9637824
TI  - Subgenus classification of Acanthamoeba by riboprinting.
AB  - Subgenus classification of Acanthamoeba remains uncertain. Twenty-three reference
      strains of Acanthamoeba including 18 (neo)type-strains were subjected for
      classification at the subgenus level by riboprinting. PCR/RFLP analysis of 18S
      rRNA gene (rDNA). On the dendrogram reconstructed on the basis of riboprint
      analyses, two type-strains (A. astronyxis and A. tubiashi) of morphological group
      1 diverged early from the other strains and were quite distinct from each other.
      Four type-strains of morphological group 3, A. culbertsoni, A. palestinensis, A.
      healyi were considered taxonomically valid, but A. pustulosa was regarded as an
      invalid synonym of A. palestinensis. Strains of morphological group 2 were
      classified into 6 subgroups. Among them, A. griffini which has an intron in its
      18S rDNA was the most divergent from the remaining strains. Acanthamoeba
      castellanii Castellani, A. quina Vil3, A. lugdunensis L3a, A. polyphaga Jones, A.
      triangularis SH621, and A. castellanii Ma strains belonged to a subgroup, A.
      castellanii complex. However, A. quina and A. lugdunensis were regarded as
      synonyms of A. castellanii. The Chang strain could be regarded as A. hatchetti.
      Acanthamoeba mauritaniensis, A. divionensis, A. paradivionensis could be
      considered as synonyms of A. rhysodes. Neff strain was regarded as A. polyphaga
      rather than as A. castellanii. It is likely that riboprinting can be applied for
      rapid identification of Acanthamoeba isolated from the clinical specimens and
      environments.

PMID- 9637825
TI  - The first discovery of larval Gnathostoma hispidum (Nematoda: Gnathostomidae)
      from a snake host, Agkistrodon brevicaudus.
AB  - The present study was performed to observe the infection status of several kind
      of animals with indigenous Gnathostoma in Korea, and morphological
      characteristics of gnathostome larvae detected from pit-viper, Agkistrodon
      brevicaudus, for the species identification. To know the existence of Gnathostoma
      in Korea, 3,450 loaches, 24 bullfrogs, several kinds of snakes, i.e., 55 Elaphe
      rufodorsata, 2 Dinodon rufozonatum rufozonatum, 62 Rhabdophis tigrinus tigrinus
      and 87 Agkistrodon spp., and 438 cats were examined. A total of 21 larval
      gnathostomes was detected from 12 pit-vipers, A. brevicaudus. They were 2,233 x
      0.343 mm in average size and covered with about 210 transverse rows of minute
      cuticular spines. Their characteristic head bulbs were provided with 4 rows of
      hooklets of which average numbers in each row were 36.8, 39.0, 41.7 and 44.3,
      posteriorly. In the cross sections of midgut level, the intestinal wall consisted
      of a single layer of 19-25 elongate epithelial cells with a single nucleus. SEM
      observation of the larvae revealed unique features of head bulb, cuticular spines
      on transverse striations and a cervical papilla. On the basis of above
      morphological characteristics, they were identified as the advanced third-stage
      larvae of Gnathostoma hispidum. It was first confirmed that the pit-viper,
      Agkistrodon brevicaudus is the snake intermediate host of G. hispidum.

PMID- 9637826
TI  - Life history of Echinoparyphium recurvatum (Trematoda: Echinostomatidae) in
      Korea.
AB  - The present study was performed to observe characteristics of the life history of
      Echinoparyphium recurvatum under both natural and laboratory conditions in Korea.
      A batch of Radix auricularia coreana was collected from Sunamchon, one of the
      stream of West Naktonggang (River), in Kangso-gu, Pusan during August and
      September 1992. Out of 106 snails examined by crushing, 52 (49.0%) were infected
      with larval E. recurvatum, i.e. rediae, cercariae and metacercariae. Cercariae
      naturally shed from snails encysted in the snails of same species and loaches,
      but not in mud-snails. Adult worms were detected from chicks and ducks
      experimentally infected with metacercariae, but not from rats and mice. The
      average recovery rate of adults from chicks was 13.1%. Rediae were sac-like,
      2.437 x 0.317 mm in average size, with a muscular pharynx and a brownish cecum
      which reached the anterior half of the body. Cercariae consisted of a spindle
      shaped body (0.262 x 0.129 mm in average) and a rod-like tail (0.528 x 0.056 mm
      in average). In the cercarial body, 45 collar spines were observed on the head
      crown, and double rows of excretory ducts with fine granules were laterally
      arranged between the pharynx and the ventral sucker. Metacercariae were
      spherical, 0.144 x 0.142 mm in average size, with thick hyaline outer and thin
      elastic inner walls, and many excretory granules. Adults were slender and more
      attenuated in the anterior end, 2.760 x 0.550 mm in average size, and had 45
      collar spines including four end group spines on both ventral corners. From the
      above results, it was confirmed that R. auricularia coreana plays a pivotal role
      in the life cycle of E. recurvatum as the first and/or second intermediate hosts
      in Korea.

PMID- 9637827
TI  - Viability of eggs, filariform larvae and adults of Strongyloides venezuelensis
      (Nematoda: Strongyloidea) maintained in vitro.
AB  - The present study was performed to check the viability of eggs, filariform larvae
      and adults of Strongyloides venezuelensis exposed to various conditions for an in
      vitro maintenance. The eggs in the feces remained viable for about 25 days at 4
      degrees C and 15 days at room temperature. However, the isolated eggs in sterile
      saline lost their viability within 24 hr at 4 degrees C. The eggs in morula stage
      were very sensitive to air drying and rapidly lost their viability (< or = 12
      hr). Filariform larvae survived for a maximum period of 45 days in fecal
      suspension and 28 days in 0.12% nutrient broth in polyvinyl culture bags
      maintained at 20 degrees C. On the other hand, those isolated from nutrient broth
      cultures survived for a maximum period of 32 days in tap water and 22 days in
      sterile saline at 20 degrees C. The mature adult worms obtained from
      experimentally infected rats survived maximally for 9 days in serum supplemented
      (10% rat-serum) 0.12% nutrient broth and 4 days in serum free nutrient broth at
      37 degrees C while the culture media were changed at an alternate day. The adult
      female worms deposited fertile eggs in serum supplemented and serum free nutrient
      broth cultures, however, the hatched larvae (L1) were not able to develop to the
      filariform stage in the culture media and found to die within 24 hr of
      maintenance. The present findings on an in vitro maintenance of different stages
      of S. venezuelensis may provide useful information for biological and biochemical
      studies with Strongyloides species.

PMID- 9637828
TI  - Intestinal mastocytosis and goblet cell hyperplasia in BALB/c and C3H mice
      infected with Neodiplostomum seoulense.
AB  - Mucosal mast cell (MMC) and goblet cell (GC) responses were observed in the small
      intestine of two strains of mice (BALB/c and C3H) infected with Neodiplostamum
      seoulense, and their roles in the host defense and worm expulsion were studied.
      From day 3 to 28 post-infection (PI) with 200 metacercariae, the worm recovery
      rate from BALB/c mice was consistently and remarkably higher than that from C3H
      mice. In the duodenum of both strains of mice, the main habitat of the flukes,
      mastocytosis was pronounced on day 7 PI but quickly diminished thereafter.
      Similar kinetics were observed in the jejunum and ileum, although the extent of
      mastocytosis was lesser in the ileum than other two areas. These MMC kinetics
      were not different between the two strains of mice. Moreover, the extent of
      mastocytosis was stronger in BALB/c mice than in C3H mice. GC hyperplasia was
      remarkable in the duodenum of BALB/c mice throughout the course of infection
      except day 14 PI, whereas it was recognizable only in the jejunum and ileum of
      C3H mice on day 7 PI. Mucin activation was evidently demonstrated in both strains
      of mice throughout the course of infection, but more marked in BALB/c than in C3H
      mice. The results strongly suggest that mastocytosis and GC hyperplasia are local
      immune responses against N. seoulense, however, they play a minor role in the
      host defense and worm expulsion.

PMID- 9637829
TI  - Immunosuppressive effect of Cryptosporidium baileyi infection on vaccination
      against Newcastle disease in chicks.
AB  - Hemagglutination-inhibition titers (log2) to Newcastle disease (ND) virus were
      chronologically observed in chicks, which were orally inoculated with 5 x 10(5)
      oocysts of Cryptosporidium baileyi at 2 days of age and subsequently vaccinated
      with inactivated ND virus at 4 and 21 days postinoculation. In general, the
      titers were considerably lower in the infected chicks than those in the
      uninfected control throughout the experimental period (p < 0.01), and rapid
      negative seroconversions were observed in the infected chicks. The titers reached
      a peak on weeks 2 and 4 post-booster-vaccination in the control and infected
      chicks, respectively. Thus, C. baileyi infection was shown to have an
      immunosuppressive effect on ND vaccination when the agent was given to 2-day-old
      chicks. It is suggested that C. baileyi infection in chicks may increase the host
      susceptibility to ND virus.

PMID- 9637830
TI  - The effect of heterogeneous hyperimmune IgG antibody on prophylaxis and treatment
      of Pneumocystis carinii infection in rats.
AB  - Immunotherapy has been used in support of trimethoprim-sulfamethoxazole treatment
      for Pneumocystis carinii pneumonia. The present study investigated the
      therapeutic or preventive effects of heterogeneous hyperimmune IgG antibody (HIA)
      in experimental rats. Their immunity was suppressed by steroid injection, and
      they were also injected peritoneally with HIA which reacted with 40-55, 92, 116,
      and 200 kDa bands of the crude antigen. All rats were infected by P. carinii and
      the cystic forms on lung impression smears were counted. The count was 20.5-76.5
      (mean 52.5 + 19.3) in those which received steroid only, but decreased to 6.0
      21.0 (mean 13.5 + 10.6) in those of group 3 which received HIA for the same
      duration. In other groups, the mean count ranged from 29.9 + 32.9 to 54.1 + 47.7,
      and in those which received 13.7 mg HIA the reduction effect was greater than in
      those which received 6.8 mg or 20.5 mg HIA. The present finding confirmed that in
      rats during the early stage of infection, the heterogeneous HIA to MSG antigen
      bands had a partial effect on P. carinii pneumonia, both prophylactically and
      therapeutically.

PMID- 9637831
TI  - Isolation and characterization of a 40 kDa cysteine protease from Gymnophalloides
      seoi adult worms.
AB  - A 40 kDa cysteine protease was purified from the crude extract of adult worms of
      Gymnophalloides seoi by two consecutive steps: Sephacryl S-200 HR and DEAE
      Sephacel chromatography. Enzyme activities were completely inhibited by cysteine
      protease inhibitors. L-trans-epoxysuccinylleucylamido (4-guanidino) butane (E-64)
      and iodoacetic acid, strongly suggesting that the purified enzyme belongs to the
      cysteine family of proteases. The enzyme was maximally active at pH 4.5 in 0.1 M
      of buffer, and its activity was greatly potentiated in the presence of 5 mM
      dithiothreitol. The protease degraded macromolecules with differential
      capabilities; it degraded extracellular matrix proteins, such as collagen and
      fibronectin, with a stronger activity against collagen than fibronectin. However,
      the enzyme digested hemoglobin and human immunoglobulins only slightly, leaving
      them nearly intact after an overnight reaction. Our results suggest that the
      cysteine protease of G. seoi adults is potentially significant in the nutrient
      uptake from the host intestine.

PMID- 9637832
TI  - A relapsed case of imported tertian malaria after a standard course of
      hydroxychloroquine and primaquine therapy.
AB  - Resistance of Plasmodium species to antimalarial agents has become increasingly
      challenging to the management and prevention of malaria. We experienced an
      imported case of tertian malaria due to Plasmodium vivax relapsed after a
      seemingly successful treatment with conventional course of hydroxychloroquine and
      primaquine. A 35-year-old man developed fever three days after return from India
      and mainland China. After his illness was diagnosed as tertian malaria, he was
      managed with hydroxychloroquine and then primaquine (primaquine base 15 mg/day
      for 14 days). Thereafter peripheral blood smears showed no malarial parasites,
      and there was no relapse of symptom until the 55th post-treatment day, however,
      six months after the above treatment tertian malaria relapsed. He was managed
      with the same medications again and malaria did not relapse for 10 months.

PMID- 9637833
TI  - Detection of Cryptosporidium oocysts in canine fecal samples by
      immunofluorescence assay.
AB  - Fecal samples were collected from 257 dogs in four areas in Korea during the
      period of January 1996 to November 1997 and examined by immunofluorescence assay
      for Cryptosporidium oocysts using a commercial diagnostic kit (Meridian
      Diagnostics, Cincinnati, Ohio). Of the 257 samples, 25 (9.7%) were positive for
      Cryptosporidium. Differences were noted in the prevalence of canine
      cryptosporidiosis in both areas and dog types. The results provide a further
      evidence of environmental contamination and widespread distribution of the
      parasite in Korea.

PMID- 9637834
TI  - [One-stage repair of interrupted aortic arch with selective cerebral perfusion].
AB  - To minimize the neurological compromise after the circulatory arrest, the
      selective cerebral perfusion could be beneficial. We underwent one-stage repair
      of the interrupted aortic arch (IAA) with various intracardiac anomalies for the
      six patients, age ranging from 12 days to 4 months, by using the selective
      cerebral perfusion. Cardiopulmonary bypass was established by using two-way
      arterial cannulation supported by the two respective pump systems, one of which
      utilized the EPTFE graft anastmosed to either the bracheocephalic artery or the
      right subclavian artery and second of which enrouted through the arterial ductus
      to the descending aorta. The cerebral perfusion during the circulatory arrest for
      the aortic arch repair was maintained by the selective perfusion via EPTFE graft
      with 10 ml/kg/min blood flow. After the completion of the arch repair, the total
      system perfusion was restarted through the graft and the repair of the
      intracardiac anomalies was followed. Of six, no operative death or neurological
      complications related to the operation were found. The clinical neurological
      evaluation after operation also demonstrated the normal for the age. In
      conclusion, the selective cerebral perfusion by using the EPTFE graft during the
      circulatory arrest might decrease the risk of brain damage.

PMID- 9637835
TI  - [A case of fulminant myocarditis treated by ABIOMED BVS 5000 biventricular
      support].
AB  - Reported is a case of acute fulminant myocarditis with profound circulatory
      compromise. The patient was supported with biventricular assist devices (BVS 5000
      ; ABIOMED Inc., Danvers, Mass.). The patient had remarkable recovery of
      ventricular function, which allowed for the removal of the device after 269 hours
      of support and the recovery to the normal quality of life. This case shows the
      success of mechanical support to treat potentially fatal disease process.

PMID- 9637836
TI  - [Three cases of pulmonary dirofilariasis suspected of lung cancer].
AB  - We experienced with three patients with pulmonary dirofilariasis found in
      resected lungs. Two patients showed abnormal shadows on chest roentgenograms
      without symptoms. Another patients had chest discomfort. All patients underwent
      diagnostic thoracotomy. Histopathological examination showed necrotic
      granulomatous lesions surrounded by fibrous tissue and transverse section of
      Dirofilaria immits was found. It has been an increasing reported disease. It is
      important to keep in mind the possibility of dirofilariasis.

PMID- 9637837
TI  - [A case report of pulmonary embolectomy using an endoscope for the detection of
      residual emboli].
AB  - A 61-year-old woman was transferred to our hospital because of palpitation,
      tachypnea and repeated syncopal attack. On admission, sinus tachycardia and
      hypoxia were noted without deterioration of consciousness. The diagnosis of
      pulmonary embolism was made by pulmonary angiography and right heart
      catheterization showing multiple pulmonary emboli and pulmonary hypertension. An
      emergent pulmonary embolectomy was performed under total cardiopulmonary bypass.
      Residual emboli of bilateral pulmonary arteries were detected with a fiberoptic
      choledochoscope and removed carefully with forceps. Pulmonary angioscopic
      evaluation appears to be safe and useful for direct visual detection of emboli
      and completion of embolectomy.

PMID- 9637838
TI  - [Primary large cell carcinoma of the lung in the patients undergoing pulmonary
      resection: a comparison between pre- and post-operative diagnosis].
AB  - Between 1981 and 1995, 591 patients with primary lung cancer underwent
      operations. Of these, 19 patients (3.2%) was diagnosed as a large cell carcinoma
      pathologically. Clinicopathologically, we analyzed a discrepancy between pre- and
      post-operative diagnosis of these patients. This study showed as follows: 1)
      Accuracy of preoperative diagnosis was 73.7%; 2) No patients with primary site in
      right upper lobe had a correct diagnosis; 3) Accuracy of preoperation was not
      depending on tumor size; 4) In retrospective findings of the biopsied specimens,
      'incomplete glandular differentation' caused preoperative diagnosis to
      adenocarcinoma, and modification of the specimens by pneumonia caused it to
      squamous cell carcinoma; 5) Inadequatespecimens originated from the right upper
      lobe or pneumonia lobe; 6) The five-survival rate was 27.3%.

PMID- 9637839
TI  - [The long-term anterior chest wound pain after the cardiac surgery].
AB  - We discussed on the long-term anterior chest wound pain after the cardiac surgery
      by using a questionnaire. The risk of the left anterior chest wound pain was high
      significantly in the cases using the left internal thoracic artery compared with
      other cases. Participation of the division of the left upper pericardium and the
      adjacent soft tissue was highly suggested as the cause of this pain.

PMID- 9637840
TI  - [Outcome of emergency surgery for Stanford type A aneurysms: selection of
      operative procedures and supported systems of cerebral protection].
AB  - Fourteen surgical cases of acute dissecting aneurysms of Stanford type A were
      reported. Clinical symptoms, operative methods, pathophysiology, cerebral
      protection, supported systems, and prognosis were examined. All patients
      underwent surgery within 5 days of symptom onset. The patient population
      consisted 8 males and 6 females with a mean age of 56.6 years. Ascending aortic
      replacement was performed using a vascular graft 12 patients. ECC was performed
      under deep hypothermia. Femoral artery cannulation and retrograde cerebral
      perfusions was performed in all cases. The ascending aorta was the site of entry
      in 13 of the 14 cases. Whenever feasible, enhanced CT and aortography were
      performed to confirm the entry lesion. Two patients expired. One patient died
      intraoperatively due to massive bleeding. The other patient, while hospitalized,
      experienced a cerebrovascular accident and died due to pneumonia. All other
      patients ran an uneventful post-operative course without cerebrovascular
      accident. In conclusion we think that although ascending aorta replacement using
      prosthetic grafts is not ideal for patients with Stanford type A dissecting
      aneurysms, it is a viable option for emergency cases. We found retrograde
      circulatory cerebroplegia (RCCP) to be satisfactory for brain protection during
      these emergency procedures.

PMID- 9637841
TI  - [Prospective study on evaluation of the ischemic heart disease for preoperative
      patients with lung cancer].
AB  - One hundred twenty-four patients with lung cancer undergoing operation in our
      hospital were prospectively studied on evaluation of the ischemic heart disease
      before operation. They performed master double electrocardiogram and exercised T1
      scintigram before operation. The patient with positive master double
      electrocardiogram and/or exercised T1 scintigram was taken into high risk group.
      All patients in high risk group performed coronary angiography. This high risk
      group consisted of 37 patients (29.8%), including 6 single vessel disease (4.8%),
      2 double vessel disease (1.6%), and 1 triple vessel disease (0.8%). Preoperative
      revascularization was done 8 patients (6.5%). These revascularization patients
      had uneventful course during and after lung operation. However 2 cases of
      vasospastic angina (VSA) occurred in non-risk group during operation. It was
      impossible to anticipate VSA before lung operation in our series. Therefore our
      preoperative evaluation and care of organic ischemic heart disease was effective
      in preventing cardiac complications.

PMID- 9637842
TI  - [Comparative studies of video-assisted thoracoscopic surgery versus thoracotomy
      for primary spontaneous pneumothorax].
AB  - Between April 1992 and March 1997, 32 patients with primary spontaneous
      pneumothorax were operated in our institution. In the first three years, 9
      patients underwent thoracotomy which was classified into two groups axillary
      thoracotomy group (AX group) in 5 cases and postero-lateral thoracotomy group (PL
      group) in 4 cases. In the recent two years, 23 consecutive patients underwent
      video-assisted thoracoscopic surgery (VATS group). The operating time,
      intraoperative blood loss, serum CRP and CK level, the duration of the indwelling
      chest tube, postoperative hospital stay, the duration of epidural anesthesia,
      complications and recurrences were compared among the three groups. The CRP level
      was significantly lower in VATS group than in both AX group and PL group. The
      duration of indwelling chest tube and postoperative hospital stay were
      significantly less in VATS group than in both AX group and PL group. There was no
      significant difference in complications and recurrences among the three groups We
      conclude from findings that VATS is superior to thoracotomy in the treatment of
      primary spontaneous pneumothorax. However more careful intraoperative
      manipulation is required to prevent postoperative recurrence.

PMID- 9637843
TI  - [A case report of mycotic aneurysms of descending thoracic aorta].
AB  - A rare case of mycotic aneurysms of descending thoracic aorta is presented. A 63
      year-old man was admitted with history of persistent high fever and loss of
      consciousness to our hospital. On admission, there were elevated WBC and CRP.
      Blood and spinal fluid cultures revealed growth of Streptococcus pneumonia.
      Despite of antibiotic therapy for meningitis and bacteremia, inflammatory sign
      continued, and new abnormal shadow appeared on chest X-ray. Chest CT and
      aortography showed two aneurysms of descending thoracic aorta. In an emergency
      operation, there was no abscess formation around the aneurysms. Aneurysms were
      excised en bloc without opening aneurysms followed by in situ Dacron tube graft
      replacement. The patient has been doing well without infection.

PMID- 9637844
TI  - [The long-term result of an adult case of transposition of the great arteries
      corrected with Rastelli operation at the age of thirty-two years].
AB  - A 32-year-old woman with transposition of the great arteries was referred to us
      for corrective surgery. She had severe cyanosis, dyspnea, and hemoptysis. The
      cardiac catheter study and echocardiography revealed that she had transposition
      of the great arteries, associated with atrial septal defect, ventricular septal
      defect, patent ductus arteriosus, and pulmonary stenosis. Rastelli operation was
      performed using equine pericardial roll with three valves made from autologous
      pericardium. After the operation she gave birth to two children without any
      symptom. Ventricular tachycardia occurred several times but was controlled by the
      drug. Eight years after the operation she underwent catheter study. Although the
      right ventricular pressure was 80 mmHg and the pressure gradient through the
      conduit was 38 mmHg, her general clinical condition was fairly good. We think the
      late postoperative result of this patient is satisfactory as an adult case of
      transposition of the great arteries.

PMID- 9637845
TI  - [An aortic valve-sparing procedures (remodeling) for a patient with annuloaortic
      ectasia: a case report].
AB  - A 51-year-old man with annuloaortic ectasia and aortic regurgitation, who did not
      have Marfan syndrome, underwent an aortic valve-sparing root reconstruction
      (remodeling). All three sinuses were excised and then the ascending aorta was
      replaced with a 30 mm collagen-impregnated Dacron graft, one of which ends were
      scalloped to reproduce pseudosinus. Each coronary artery orifice was anastomosed
      to the graft with Carrel patch method. Post-operative angiogram showed no aortic
      regurgitation and no pseudosinus formation, because the graft was slightly larger
      than the optimal one. The NYHA functional class has been improved III to I 18
      months after the operation.

PMID- 9637846
TI  - [An experience with St. Jude medical prosthetic 19A-HP which resulted in
      restricted opening at an early stage after operation].
AB  - St. Jude medical hemodynamic plus series is positively used for aortic valve
      replacement (AVR) of small orifice because it can increase the orifice area by
      26% compared with conventional prosthetic valves of the same size. We performed
      AVR with SJM 19A-HP on a patient having aortic stenosis with regurgitation using
      horizontal mattress suturing technique. The aortic orifice size was 18.9 mm at
      the preoperative measurement. The course after the operation was uneventful until
      9 days after the operation when cinefluoroscopy revealed symmetrical restriction
      of opening of valve leaflets. We are now monitoring the clinical course at the
      patient has not developed any symptoms though the LV-Ao pressures gradient is 60
      mmHg by Doppler echocardiography. As the restriction of valve leaflet opening was
      symmetrical, it is not likely that an excess of the ligature or remnant caused
      the restriction; structural problems of St. Jude medical prosthesis appear to be
      a more reasonable explanation. Since the orifice ring of this prosthesis is not
      reinforced, longitudinal forces applied to the hinge may alter the shape of the
      ring, thus restricting the movement of valve leaflets. In the present case,
      forced insertion of 19A-HP instead of more desirable 17-HP is considered to have
      caused longitudinal forces acting on the hinge.

PMID- 9637847
TI  - [Malignant recurrence of solitary fibrous tumor of the pleura developed 20 years
      after the surgery: a case report of re-extirpation].
AB  - A 63-year-old female developed the chest wall tumor protruding into the right
      thoracic cavity. She consulted our hospital complaining of chest pain. 20 years
      before this episode, she had undergone tumor extirpation combined with the
      partial resection of adherent anterior chest wall and the diaphragm for large
      benign solitary fibrous tumor of the pleura. Because of the difficulty in making
      diagnosis by needle biopsy, operation (re-tumor extirpation combined with the
      chest wall) was done. Histological examination revealed that the tumor was
      malignant solitary fibrous tumor. We concluded that the tumor was the malignant
      recurrence of the benign solitary fibrous tumor resected 20 years before.
      Occasionally, benign solitary fibrous tumor of the pleura recurs and behaves more
      aggressively than primary, but such a long latent period as 20 years is quite
      uncommon. So we present the case and the review of the literature.

PMID- 9637848
TI  - [A case of bronchial mucoepidermoid carcinoma treated with right sleeve middle
      lobectomy].
AB  - We reported one case of a 26-year-old woman in whom mucoepidermoid carcinoma of
      the right middle lobe bronchus was successfully treated by bronchoplasty. The
      patient complaining fever and cough was admitted to our hospital and the
      bronchoscopic examination revealed a tumor mass occluding the right middle lobe
      bronchus. Thus, sleeve middle lobectomy was performed. The histological
      examination of the resected material revealed a low-grade malignant
      mucoepidermoid carcinoma with no lymphatic metastasis. The patient has been well
      and free of recurrence for one year postoperatively. In this case, sleeve
      lobectomy is approved of an effective method for local curability and
      preservation of respiratory function.

PMID- 9637849
TI  - [Primary clear cell carcinoma of the lung: report of an operative case].
AB  - The patient was a 75-year-old man complaining of cough in July 1996. Chest X-ray
      demonstrated a tumor in the left S6. Percutaneous lung biopsy specimen revealed
      lung cancer. On September 4, 1996, left lobectomy (R 2 a) was performed. The
      tumor was 3.8 x 3.2 x 2.1 cm in size and showed a white yellow solid mass
      (pT2N0M0, pStage I, p1d0e0pm0). The pathological examination was confirmed no
      differentiation in adenocarcinoma and squamous cell carcinoma. More than 90% of
      the tumor cells were characterized as having large clear cytoplasm. On
      immunohistochemical study, the tumor cells expressed positive with EMA, CEA,
      cytokeratin and negative with vimentin. The postoperative findings showed no
      presence of renal cell carcinoma. As the result, a diagnosis of primary clear
      cell carcinoma of the lung was made. The postoperative course is uneventful.

PMID- 9637850
TI  - [An adult case of intrathoracic chest wall type lipoma by VATS resection].
AB  - A 48-year-old woman without symptoms was pointed out an abnormal shadow on chest
      X-ray film taken at the mass survey. Image diagnosis led to intrathoracic chest
      wall type lipoma. The tumor was surgically removed by video assisted
      thoracoscopic surgery (VATS), and the diagnosis of lipoma pathohistologically.
      VATS resection was an useful procedure for intrathoracic lipoma because VATS
      itself must be less invasive and lipoma was not invasive. CT and MRI were useful
      for evaluation of extent of tumor, but not effective for differential diagnosis
      of liposarcoma from lipoma. So surgical resection by VATS should be considered,
      if possible.

PMID- 9637851
TI  - [A case report on surgery for chylothorax after anterior spinal fusion:
      usefulness and effectiveness of intraoperative milk administration and
      postoperative OK-432 administration].
AB  - A 75-year-old man of chylothorax after anterior spinal fusion successfully
      underwent thoracoabdominal operation in order to ligate chyloleakage. Not only
      preoperative milk intake but also intraoperative administration of milk through
      nasogastric tube was useful for identification of the site of leakage. OK-432 was
      administered through locally placed and chest tube after operation, after which
      residual chyloleakage was stopped. lntraoperative administration of milk through
      nasogastric tube was useful and OK-432 injection through topical and chest tube
      may be effective, these should be recommended for management of chylothorax.

PMID- 9637852
TI  - Public health protection vs. informed consent.

PMID- 9637853
TI  - Cancer clusters. What role for epidemiology?

PMID- 9637854
TI  - Minnesota's elite bug busters.

PMID- 9637855
TI  - Antimicrobial resistance. Guidelines for the primary care physician.
AB  - Antimicrobial resistance is an important issue when treating patients with
      various bacterial, fungal, protozoal, and viral infections. Until recently, the
      focus of concern was on nosocomially acquired infections. However, organisms
      causing common community-acquired infections have now developed antimicrobial
      resistance. This paper provides a brief overview of this emerging global threat
      and discusses resistance in gram-positive organisms, outpatient and antibiotic
      use, and strategies to reduce antibiotic overuse. Curbing the overuse of
      antibiotics is crucial to reversing the increase in drug-resistant bacteria. We
      need to develop guidelines and educate physicians and the public on the use of
      antibiotics for respiratory syndromes with predominantly viral etiologies.

PMID- 9637856
TI  - An epidemiologic summary of the AIDS/HIV epidemic in Minnesota.
AB  - A cumulative total of 3,202 AIDS cases and 2,355 non-AIDS cases of HIV infection
      have been diagnosed in Minnesota and reported to the Minnesota Department of
      Health since 1982. The number of AIDS cases and HIV infection cases diagnosed
      annually peaked five to 10 years ago. New treatments for HIV infection have led
      to a marked reduction in mortality. The number of deaths due to AIDS/HIV in 1997
      (76) was the lowest number in Minnesota since 1986. Several trends continue to
      evolve in reported AIDS/HIV cases. First, the proportion of female cases has
      increased over time. Second, male-to-male sex remains the most common exposure
      category, but the proportion has declined over time. In contrast, the proportion
      of cases related to injecting drug use and heterosexual contact has increased
      over time. Third, an increasing proportion of AIDS/HIV patients are black.
      Although progress has been made in reducing AIDS/HIV incidence, more Minnesotans
      are living with AIDS/HIV than ever before.

PMID- 9637857
TI  - Epidemiology in Minnesota. Alcohol epidemiology. Reporting and collecting data on
      use in Minnesota.

PMID- 9637858
TI  - Etiology, prevention, and treatment of breast, prostate, colorectal, and lung
      cancer.

PMID- 9637859
TI  - Trends in cardiovascular disease in Minnesota.

PMID- 9637860
TI  - Issues in environmental health epidemiology.

PMID- 9637861
TI  - Training infectious disease epidemiologists for the next millennium. The
      epidemiology program at the University of Minnesota.

PMID- 9637862
TI  - Injury epidemiology. Prevention and control of a major public health problem.

PMID- 9637863
TI  - Occupational epidemiology in Minnesota.

PMID- 9637864
TI  - Reducing smoking among Minnesota teens in managed care. Smoking.

PMID- 9637865
TI  - The role of epidemiology in the court.

PMID- 9637866
TI  - Commerce in organ transplantation.

PMID- 9637867
TI  - Manic-depressive illness from 1936 to 1996: diagnostic modalities, social
      attitudes, and therapeutic options.

PMID- 9637868
TI  - The case of the president's polyp: portrayal of pathologists in the media.

PMID- 9637869
TI  - Can managed care be managed? Some agnostic reflections.

PMID- 9637870
TI  - Rhabdomyolysis in antiquity. From ancient descriptions to scientific explication.

PMID- 9637871
TI  - Medical cannibalism in China: the case of ko-ku.

PMID- 9637872
TI  - Dartmouth Medical School bicentennial symposium. Great issues for medicine in the
      twenty-first century: a consideration of the ethical and social issues arising
      out of advances in the biomedical sciences.

PMID- 9637873
TI  - Inequalities and antivirals.

PMID- 9637874
TI  - Fire, blood, and the lion of the Union: Joshua Chamberlain's Civil War ailments.

PMID- 9637875
TI  - Three for the record.

PMID- 9637876
TI  - The death of Socrates.

PMID- 9637877
TI  - Reflections on the question: where is the sacrifice?

PMID- 9637878
TI  - Medical role models.

PMID- 9637879
TI  - [Present state of Japan Marrow Donor Program].

PMID- 9637880
TI  - [Comparison of disease-free survival between bone marrow transplantation (BMT)
      from unrelated donor and BMT from HLA identical sibling].

PMID- 9637881
TI  - [Current status of allogeneic-peripheral blood stem cell transplantation and the
      possibility for unrelated donor-peripheral blood stem cell transplantation].

PMID- 9637882
TI  - [Future problems in cord blood transplantation].

PMID- 9637883
TI  - [New strategies and future direction in hematopoietic stem cell transplantation
      from unrelated volunteer donor].

PMID- 9637884
TI  - [A pharmacokinetic study of the value of oral cytarabine ocfosfate in the
      treatment of hematological malignancies].
AB  - Cytarabune ocfosfate (SPAC) is rapidly transformed into cytarabine (ara-C) when
      orally administered. The pharmacokinetics of SPAC was studied in six patients
      with acute non-lymphocytic leukemia (ANLL) and/or myelodysplastic syndromes (MDS)
      after oral administration of SPAC at 100 to 400 mg/day for 14 days. Plasma ara-C
      concentrations reached a plateau in 48 to 96 hours after initiation of SPAC
      administration, remained at this or a little higher level until one day after its
      termination and were less than 1 ng/ml 8 days after the termination. From all of
      pharmacokinetic data, the oral administration of SPAC at 150 to 300 mg/m2/day was
      pharmacokinetically concluded to be comparable to the continuous infusion of ara
      C at 20 mg/m2/day. All of the patients could receive SPAC for 14 days. SPAC is
      considered to be useful for consolidation or maintenance chemotherapy of ANLL or
      MDS outpatients who are unable to undergo intensive chemotherapy.

PMID- 9637885
TI  - [Peripheral blood stem cell transplants: clinical considerations and observations
      in practice in a general hospital].
AB  - Of 36 patients with malignant tumors who had been subjected to peripheral blood
      stem cell harvests (PBSCHs), 22 had undergone peripheral blood stem cell
      transplants (PBSCTs) since 1993. Flow cytometry recorded higher CD34+ cell yields
      in the PBSCHs of those patients with high white blood cell (WBC) counts as well
      as those who had been under intensive chemotherapy. Also, higher CD34+ cell
      yields were recorded in patients whose peripheral blood WBCs recovered more
      rapidly from their nadir state. WBC counts recovered rapidly in patients who
      received transfusions of at least 2.0 x 10(6) CD34+ cells/kg. However, patients
      with acute non-lymphocytic leukemia (ANLL) demonstrated a delayed recovery in
      their platelet counts following PBSCT. The mean disease-free survival rate and
      mean disease-free period were 60% and 12.8 months for the 5 patients with ANLL;
      and 100% and 11.3 months for the 4 patients with acute lymphocytic leukemia.
      These findings suggest PBSCT is a safe and effective treatment for patients with
      malignant tumors following high-dose chemotherapy, and can be performed in a
      private general hospital.

PMID- 9637886
TI  - [All-trans retinoic acid was effective for marked skin infiltration in a relapsed
      acute myelogenous leukemia (AML-M2) patient with t(12; 17)].
AB  - A 64-year-old man who had taken acute myelogenous leukemia (AML-M2) in 1989 have
      relapsed with t(12; 17) (p13; q11.2-21) chromosomal abnormality and presenting
      marked infiltration to the skin in 1994. Blasts were seen on his peripheral blood
      smear (15%) and bone marrow examination showed increased leukemic cells (56%),
      with maturation. Leukemic cells expressed CD13 and CD33 antigen but not HLA-DR.
      Although leukemic cells had not promyelocytic feature morphologically, detection
      of PML/RAR alpha infusion signal of peripheral leukemic cells were positive for
      8% (1% for control) by fluorescence in situ hybridization method. Because he did
      not response to standard combination chemotherapy and because we considered the
      possibility that t(12; 17) (p13; q11.2-21) observed in this case are t(15; 17)
      variant, we tried all trans retinoic acid (ATRA) to him. Interestingly, ATRA was
      very effective for skin lesion but hematologically it had no effect at all, and
      he died because of bacterial pneumonia.

PMID- 9637887
TI  - [Successful double peripheral blood stem cell transplantation for patient with
      malignant lymphoma of primary induction failure].
AB  - Three patients with non-Hodgkin's lymphoma of intermediate-grade histologies, who
      had failed to achieve a complete remission (CR) after more than several courses
      of conventional chemotherapy were treated with two cycles of high-dose
      chemotherapy with autologous peripheral blood stem cell transplantation (double
      PBSCT). All patients received regimen A with carboplatin 1g/m2, etoposide 1.2g/m2
      and cyclophosphamide 120mg/kg prior to 1st PBSCT and obtained a partial
      remission. One patients received regimen A and two patients received regimen B
      with MCNU 500mg/m2, etoposide 750mg/m2 and L-PAM 140mg/m2 prior to 2nd PBSCT and
      all patients obtained CR. Second PBSCT was performed 3 to 5 months after the 1st
      PBSCT. At a median follow-up of 36 (range; 29 to 54) months, all patients
      remained in continuous CR. The period after reinfusion of PBSCT to achieve a
      neutrophil count more than 500/microliters ranged between 7 and 9 days and to
      achieve a platelet count more than 5 x 10(4)/microliters ranged 12 and 22 days.
      Grade 3 nonhematologic toxicity (mucositis) was seen in one patient after 2nd
      PBSCT. Double PBSCT could be well tolerated with a high response rate in patients
      with malignant lymphoma of primary induction failure.

PMID- 9637888
TI  - [Hemostatic evaluation of a patient with haloperidol-induced neuroleptic
      malignant syndrome associated with disseminated intravascular coagulation].
AB  - A 94-year-old man who had been admitted to our hospital for the treatment of
      senile dementia and restless behavior exhibited consciousness disturbances, acute
      respiratory failure, high fever, and thrombocytopenia the day after receiving
      haloperidol as prescribed by a psychiatrist. On the fourth day following
      administration of haloperidol, acute renal failure with rhabdomyolysis and
      disseminated intravascular coagulation (DIC) developed in the patient, who was
      accordingly given a diagnosis of haloperidol-induced neuroleptic malignant
      syndrome (NMS) associated with DIC. He was then given heparin and antithrombin
      III, and his DIC symptoms improved soon thereafter. Elevated plasma levels of
      tissue factor and tumor necrosis factor-alpha (TNF-alpha) were sustained during
      this therapy course. Other cytokines, including interleukin IL-1 beta, IL-2 and
      IL-6, were not elevated. There are activation of extrinsic coagulation and an
      elevated level of TNF-alpha during acute renal failure and rhabdomyolysis
      associated with NMS, which is thought to trigger the onset of DIC.

PMID- 9637889
TI  - [A fatal case of aggressive-phase multiple myeloma with ileus and invasion into
      extramedullary organs].
AB  - A 62-year-old woman with IgA-lambda type monoclonal gammopathy had been followed
      up since January 1988. In March 1991, multiple myeloma (IgA-lambda) was diagnosed
      on the basis of bone marrow biopsy findings and increased serum IgA levels. She
      was treated intermittently with melphalan and prednisolone over a perioa of about
      6 years, but was eventually admitted due to renal dysfunction, hypercalcemia,
      increased serum IgA and the formation of subcutaneous masses. During chemotherapy
      she underwent emergency surgery for obturative ileus. Histological examination of
      the resected tissues revealed invasion of myeloma cells into the small intestine
      and peritoneum. Despite continued chemotherapy, the patient's soft tissue masses
      enlarged, and new lesions appeared in other organs. In the terminal stage, lower
      serum IgA levels were observed despite an increase in Bence-Jones protein levels
      in urine. The patient died five months after admission. An autopsy found
      infiltration by atypical myeloma cells in multiple organs. An immunohistochemical
      examination revealed and increase in lambda-light chain positive cells relative
      to the number of alpha-heavy chain positive cells. The terminal course was
      considered to be representative of aggressive phase multiple myeloma. The case
      was rare in that the patient's ileus was caused by invasion of myeloma cells into
      the small intestine.

PMID- 9637890
TI  - [Hereditary spherocytosis associated with severe hypophosphatemia in patients
      recovering from aplastic crisis].
AB  - This is a report about two cases of hereditary spherocytosis complicated by
      severe hypophosphatemia, while recovering from aplastic crisis. Case #1: A 31
      year-old male, who had jaundice and splenomegaly since the age of 15 and who has
      a son diagnosed with hemolytic anemia, was admitted because of fever
      lymphadenopathy, and jaundice. A diagnosis of hereditary spherocytosis was made
      based on microspherocytes observed in his peripheral blood smear. After
      admission, the anemia became more serious for a few days and he was considered
      suffering from bone marrow aplastic crisis. His serum phosphorus level fell to
      0.5 mg/dl on the second day, but it rapidly returned to normal as reticulocyte
      counts rose. Case #2: A 29-year-old male with known transient jaundice and
      splenomegaly suffered from fever, anemia and jaundice, but recovered two weeks
      later. Laboratory examination revealed positive human Parvovirus B19 (HPV-B19)
      DNA, anti-HPV-19 IgM and IgG-antibody. His serum phosphorus level fell to 1.2
      mg/dl on the eighth day, but it rose in the same manner as seen in case #1. The
      fall in serum phosphorus is probably due to its shift to the erythroblasts during
      erythroid hyperplasia.

PMID- 9637891
TI  - [Hemophagocytic syndrome due to miliary tuberculosis in the course of aplastic
      anemia].
AB  - We report a 63 year-old female with aplastic anemia (AA) who was complicated with
      hemophagocytic syndrome induced by systemic miliary tuberculosis. Two years
      before admission to our hospital, she was diagnosed as AA and had been treated
      with granulocyte colony-stimulating factor, erythropoietin and methenolone
      acetate. In May, 1996, She was transferred to our hospital because of high fever
      and exacervation of pancytopenia. She showed severe pancytopenia, and an increase
      in macrophages showing remarkable erythrophagocytosis and decrease in hemopoietic
      cells in the bone marrow. In initial examination, high titer of IgM antibody to
      herpes simplex virus type I was identified and methylprednisolone pulse therapy
      was started under the diagnosis of virus associated hemophagocytic syndrome. Ten
      days later, however, she died for intestinal hemorrhage followed by multiorgan
      failure. In autopsy, multiple epitheloid cell granulomas with acid-fast bacilli
      were found in bone marrow, lungs, liver, spleen and kidneys.

PMID- 9637892
TI  - [Acute myelogenous leukemia with hyperkalemia induced by pentamidine
      administration].
AB  - A 27-year-old male with acute myelogenous leukemia received an allogeneic bone
      marrow transplantation (allo-BMT). Pneumocystis carinii pneumonia developed on
      day 65 after the allo-BMT. The patient was intravenously treated with
      pentamidine. This resulted in a prompt improvement of his dyspnea and fever, but
      hyperkalemia occurred during the pentamidine therapy. Treatment with pentamidine
      was stopped and emergent treatment was started. Nevertheless, the serum potassium
      level rose to 7.7 mEq/l. Urgent dialysis was performed and the serum potassium
      level fell to 5.0 mEq/l after treatment. Careful monitoring of the serum
      potassium level is recommended during intravenous therapy with pentamidine.

PMID- 9637893
TI  - [A retrospective study on the development of inhibitors in Japanese hemophiliacs
      (second report, 1994 study). Research Group of Blood Products for Hemophilia
      Inhibitor].
AB  - In this report, we discuss the findings of a 1994 retrospective study concerning
      the rate of inhibitor formation in Japanese hemophiliacs. The study was the
      second of its kind, following on the first in 1991 (Kamiya et al. 1995 Int. J.
      Hematology). The records of 77 medical institutions were examined. Inhibitors
      were found in 6.50% (140 of 2154) of the patients with hemophilia A (HA), and
      5.21% (22 of 422) of those with hemophilia B (HB). The median age for antibody
      formation was 10.7 years in patients with HA, and 4.5 years in those with HB. The
      median period (exposure period) from initial plasma factor concentrates exposure
      to inhibitor formation was 46 days and 20 days, respectively, in the HA and HB
      patients. Among the HA inhibitor patients, those with a large deletion or a
      nonsense mutation were aged 17.4 years or less (0.58, 1.7, 3.5, 5.5, 7.0 and
      17.4), whereas those with intron 22 inversion were aged 55.7 years or less (1.3,
      1.3, 1.8, 33.0, 36.1, 37.7, 43.9, 47.9 and 55.7).

PMID- 9637894
TI  - [Study on EEG patterns of schizophrenics--with use of FFT dipole approximation].
AB  - EEG recording were performed in 22 non-treated schizophrenics; subsequently, the
      combination of traditional EEG frequency analysis with FFT Dipole Approximation
      as a new method for EEG analysis was employed to determine power spectra of
      baseline EEGs and three dimensional model dipole source location in anterior
      posterior, left-right and superior-inferior directions with changing the
      frequency by 0.5 Hz. Quantitative EEG study included comparison of baseline EEGs
      between normal volunteers and schizophrenics; the results obtained in this study
      coincided with previous and reports in increase of slow wave, decrease of alpha
      band and increase of fast wave. Dipole source location in schizophrenics were
      generally shifted more towards superior and posterior areas compared with those
      in normal volunteers whereas no shifts towards left-right areas were evidenced in
      schizophrenics. Seven patients on monotherapy of haloperidol were subjected to
      determination of dipole source location two weeks after commencement of the
      medication. After treatment, the source locations shifted towards anterior and
      inferior area, approaching to the dipole source locations in normal volunteers.
      Baseline dipole source locations were negatively correlated with both positive
      symptom rating score and negative symptom rating score according to BPRS,
      indicating that with increasing positive symptom rating score, the source
      location shifted towards posterior direction, and higher negative symptoms rating
      scores were associated with a shift towards right direction. These findings
      support our view that negative symptoms and positive symptoms might be associated
      with frontal lobe dysfunction theory and temporal lobe dysfunction theory.

PMID- 9637895
TI  - [Psychopathological study on "hallucination of soliloquy" in a case of
      schizophrenia].
AB  - We present what appears to be the first reported case of schizophrenia with
      hallucinatory soliloquy. An appropriate name for this symptom might be
      "hallucination of soliloquy." A thirty-year-old man had been laboring under
      delusions of persecution and auditory hallucinations in the form of being blamed
      by others after changing his job at the age of twenty-eight. He consulted our
      hospital because of unintentional "soliloquy." He complained that he had been
      maltreated in his new work place and that this stress made him talk to himself.
      The contents of his "soliloquies" were nonsensical; for example, he would grumble
      about his colleagues or the plot of a teleplay that he had seen the previous day.
      During his "soliloquies" he had the vivid sensation of both speaking and hearing
      his own voice, but the episodes actually lacked vocalization. As a result of
      therapy, the patient's disorder gradually shifted from "soliloquy" to "silent
      soliloquy," then to "breathing hard," before finally disappearing. We are aware
      of a similar symptom, "delusion of soliloquy" (Y. Kasahara et al.), in which the
      patient believes that he unintentionally spoke to himself and that everyone
      learned his secrets through his soliloquy. In comparison, our "hallucination of
      soliloquy" is unique in that it is an abnormal experience of both speaking and
      hearing. From the viewpoint of traditional symptomatology, "hallucination of
      soliloquy" is composed of auditory hallucinations, which are experiences of
      hearing, and psychomotor hallucinations, which are experiences of speaking. In
      other words, it is a simultaneous experience of both thought resonance and
      "hallucination verbale psychomotrice" (J. Seglas) or "Halluzination des
      Muskelsinns" (A. Cramer) of the speech apparatus. However the overall concept of
      "hallucination of soliloquy" deviates from both thought resonance and
      "hallucination verbale psychomotrice" or "Halluzination des Muskelsinns." For a
      different point of view, we refer to L.S. Vygotsky's studies on inner speech. A
      comparison of "hallucination of soliloquy" with inner speech suggests that
      "hallucination of soliloquy" is "inner speech which is converted into outer
      speech" or "egocentric speech without vocalization." S. Kato notes that two
      patterns are found in the schizophrenic discourse, mirroring discourse and
      deviant discourse, which are named after mirroring and deviant characters
      concerning the ordinary linguistic code. The former simulates the ordinary
      linguistic code. In mirroring discourse, the patient almost literally imitates
      and repeats customary discourse such as an authority's speech or television. The
      latter is characterized by deviation from human actuality or the existing
      linguistic code and is represented by delusions, neologisms, and incoherent
      speeches. It has been suggested that mirroring discourse has moments of return to
      actuality, while in deviant discourse the patient remains entirely in the
      delusional world. It is said that discourse is realized in the deviant mode in
      the case of ordinary auditory hallucinations. In the case of "hallucination of
      soliloquy," the discourse occurs in the patient's own mind and is spoken through
      his own mouth, in short, it is realized in mirroring mode. We conclude that
      "hallucination of soliloquy" has the characteristic of mirroring discourse, which
      is realized in mirroring mode. We suggest that "hallucination of soliloquy" is
      schizophrenic auditory hallucination that has self-healing moments.

PMID- 9637896
TI  - The Web, communication trends, and children's health. Part 4: How children use
      the Web.
AB  - Children are embracing the Internet and the World Wide Web. How are they using it
      and what do they find? This article, the fourth in a five-part series, explores
      the "whys" and the "wherefores" of children's Web use. Included are online
      recourses geared specifically for children, including health, educational, and
      entertainment sites.

PMID- 9637897
TI  - Randomized, single-blinded comparative study of the efficacy of amoxicillin (40
      mg/kg/day) versus standard-dose penicillin V in the treatment of group A
      streptococcal pharyngitis in children.
AB  - A 10-day course of amoxicillin at a dosage of 40 mg per kilogram per day was
      compared with conventional (lower dosage) penicillin V therapy in the treatment
      of culture-proven Group A streptococcal pharyngitis in children 3 to 18 years of
      age in a prospective, randomized, and single-blinded study. Children had to have
      signs and symptoms compatible with the diagnosis of streptococcal pharyngitis and
      to have a throat swab positive for Group A streptococci. A second throat culture
      was obtained 10 to 14 days after the completion of therapy. Serotyping was
      performed to help differentiate carrier states from reinfections. Of 161 children
      enrolled, 113 were evaluable; 55 received penicillin and 58 received amoxicillin.
      At the completion of therapy 70.9% (39/55) of patients in the penicillin group vs
      87.9% (51/58) of patients in the amoxicillin group were asymptomatic (clinical
      cure, P = 0.025). At the completion of therapy, 54.5% (30/55) of patients in the
      penicillin group vs 79.3% (46/58) of patients in the amoxicillin group had
      negative throat cultures (bacteriologic cure, P = 0.005). The carrier rate
      (children who were well but who were still carrying the same serotype of Group A
      streptococcus) also differed between the groups: 13 (23.6%) in the penicillin
      group compared with six (10.3%) in the amoxicillin group. Amoxicillin at 40
      mg/kg/day was significantly more effective than lower dosages of penicillin V for
      clinical and bacteriologic cure in the treatment of Group A streptococcal
      pharyngitis in children. The current perception that penicillin is declining in
      effectiveness may be due to inadequate dosing.

PMID- 9637898
TI  - Hypophosphatemia in malnourished children during refeeding.
AB  - Hypophosphatemia in malnourished children during nutritional recovery (refeeding
      hypophosphatemia) is recognized as a cause of morbidity and mortality in
      adolescents with anorexia nervosa but has been only rarely reported to occur in
      younger children with other diagnoses. Over a 6-year period, we encountered three
      cases of refeeding hypophosphatemia in malnourished children admitted to a
      pediatric rehabilitation hospital. Two children had neurologic dysphagia and one
      had been starved by an abusive parent. The one patient who was symptomatic had
      obtundation, hemolytic anemia, rhabdomyolysis, and hepatocellular injury that
      began during refeeding and resolved with treatment. The signs and symptoms,
      pathophysiology, and treatment of refeeding hypophosphatemia are reviewed.

PMID- 9637899
TI  - Earlier discharge of infants from neonatal intensive care units: a pilot program
      of specialized case management and home care. Delaware Valley Child Health
      Alliance.
AB  - A multidisciplinary approach using a neonatology independent physicians
      association, affiliated hospitals, a pediatric home care company, and a health
      maintenance organization was designed to promote earlier safe discharge of
      infants from intensive care. This pilot project involved 43 infants who received
      case management and early discharge home with home oxygen, monitoring,
      intravenous antibiotics, gavage feedings, phototherapy, or nutritional management
      for poor weight gain. A staff neonatologist remained the primary physician until
      the patient would have been discharged according to standard criteria. Two
      patients had unscheduled readmissions and all infants survived. This approach
      resulted in an estimated savings of 456 hospital days and $329,982; 89% of
      parents rated the care as good to excellent, and 83% were satisfied with the
      program and outcome. This study suggests that a prospectively designed program
      can be designed to promote safe earlier discharge of infants in intensive care.

PMID- 9637900
TI  - Pitfalls in the diagnosis of aerodigestive tract foreign bodies.
AB  - In the young child, particularly those between the ages of 1 and 3 years,
      aerodigestive tract foreign bodies continue to be a significant problem. Early
      diagnosis and treatment can decrease morbidity and length of hospital stay in
      these children. Three cases of delayed diagnosis in children with bronchial (2)
      and esophageal (1) foreign bodies are presented. In dealing with young children
      it is important to maintain a high clinical suspicion of a foreign body and to
      perform a detailed history and physical examination. Options in radiographic
      analysis of the patient with a suspected foreign body, probable locations of the
      foreign body, and the likelihood of definitive radiographic findings are
      discussed. Importantly, a negative radiographic analysis does not rule out the
      presence of an aerodigestive tract foreign body. Two flow charts for the
      evaluation of patients who have possibly ingested or inhaled a foreign body are
      presented to aid the primary care physician in diagnosis.

PMID- 9637901
TI  - Evaluation of boys with marked breast development at puberty.
AB  - During the 10-year period from 1979 to 1988 we evaluated 60 boys who were more
      than 9 years old and who had significant breast development (greater than 4 cm in
      diameter) around the time of puberty. An endocrine abnormality was identified in
      seven subjects. The pathology included Klinefelter's syndrome; 46,XX maleness;
      primary testicular failure; partial androgen insensitivity; fibrolamellar
      hepatocarcinoma; and increased aromatase activity. Eight of the remaining 53
      subjects had underlying medical problems, five of them having neurologic
      disorders. The 45 remaining subjects were considered to have significant
      idiopathic gynecomastia, a condition sometimes referred to as macromastia. These
      boys tended to be both taller and heavier than average, the mean Z score for
      height being 1.4 SDs above the mean and the mean weight score being 2.7 SDs above
      the mean. This study underscores the observation that pathologic causes of marked
      pubertal gynecomastia are unusual. However, the potential for significant health
      problems among boys with marked breast development supports the need for an
      endocrine evaluation of all affected subjects. Our data also indicate that boys
      with marked idiopathic breast development have greater body mass than other boys
      of similar age. This may contribute in part to the greater breast development in
      these subjects.

PMID- 9637903
TI  - An unusual source of lead poisoning.

PMID- 9637904
TI  - Long-term prognosis of acute renal failure in the full-term neonate.

PMID- 9637902
TI  - Deep venous thrombosis in a preterm newborn of a mother with activated protein C
      resistance.

PMID- 9637905
TI  - Neonatal acute renal failure: the need for long-term follow-up.

PMID- 9637906
TI  - Head lice therapy revisited.

PMID- 9637907
TI  - "Anti-cancer gene found".

PMID- 9637908
TI  - The Frizzled CRD domain is conserved in diverse proteins including several
      receptor tyrosine kinases.

PMID- 9637909
TI  - The Wnt receptor CRD domain is also found in MuSK and related orphan receptor
      tyrosine kinases.

PMID- 9637910
TI  - Bacterial motility: secretory secrets of gliding bacteria.
AB  - Many bacteria glide over surfaces without the aid of flagella. Gliding is still
      somewhat mysterious, but recent studies show that it involves specialized
      secretory systems that assemble membrane-associated filaments, and the
      recognition of extracellular components that trigger movement via transmembrane
      transducers.

PMID- 9637911
TI  - Neurophysiology: electrically evoking sensory experience.
AB  - Monkeys trained to distinguish touch stimuli that 'flutter' with different
      frequencies can similarly distinguish electrical stimulation of the somatosensory
      cortex according to its frequency; the implication is that the electrically
      evoked patterns of cortical activity cause flutter sensations similar to those
      induced by touch.

PMID- 9637912
TI  - Organogenesis: Drosophila goes gonadal.
AB  - In many animals, germ cells migrate to the gonad to assemble into a functional
      organ. Recent work in Drosophila has built a picture of the gene activities that
      specify the gonad and allow it to attract germ cells, and has led to the
      identification of a gene, columbus, that may encode the attractive factor.

PMID- 9637913
TI  - Anti-apoptosis therapy: a way of treating neural degeneration?
AB  - Many degenerative diseases involve apoptotic cell death--can they be treated with
      apoptosis inhibitors, while protecting the normal physiological function of the
      rescued cells? Reason for optimism comes from a recent study of mutant flies with
      an analogue of the human degenerative disease retinitis pigmentosa.

PMID- 9637914
TI  - Transcription: gene control by targeted histone acetylation.
AB  - A transcriptional regulator in yeast, Gcn5p, activates transcription by targeted
      acetylation of specific lysine residues in the amino-terminal tails of histones.
      This targeted modification is restricted to nucleosomes assembled on the
      promoters of Gcn5p-responsive genes.

PMID- 9637915
TI  - Mechanosensation: swimming round in circles.
AB  - Studies of inherited deafness disorders in mice and humans are providing new
      insights into the basis of hair-cell mechanosensitivity; this enterprise has been
      joined by large-scale genetic screening in the zebrafish, where a number of
      intriguing mutants defective in mechanosensation have recently been described.

PMID- 9637916
TI  - Prostate cancer: new therapies in the pipeline?
AB  - Cancer of the prostate gland is the highest unavoidable cause of cancer mortality
      in men. The recent identification and characterisation of genes specifically
      expressed in prostate cancer helps us to understand its molecular basis and
      should offer new therapeutic avenues to combat this disease.

PMID- 9637917
TI  - Olfactory G proteins: simple and complex signal transduction.
AB  - In both vertebrates and invertebrates, olfactory perception is mediated by G
      protein-coupled receptors. Recent work, in both mouse and Caenorhabditis elegans,
      sheds light on the role of specific G proteins in olfactory signal transduction,
      neuronal morphology and axon guidance.

PMID- 9637918
TI  - Identification of the basolateral targeting determinant of a peripheral membrane
      protein, MacMARCKS, in polarized cells.
AB  - BACKGROUND: Although the molecular determinants that specify the targeting of
      transmembrane proteins to the apical or basolateral membrane domains within
      polarized epithelial cells have been well characterized, very little is known
      about the targeting of peripheral membrane proteins within these cells. MacMARCKS
      is a member of the MARCKS family of protein kinase C (PKC) substrates. This
      myristoylated protein regulates actin structure at cell membranes and is
      essential for the morphogenic movement of neuroepithelial cells during the
      formation of the neural tube. RESULTS: MacMARCKS was specifically targeted to
      sites of cell-cell contact in the basolateral domain of polarized Madin-Darby
      canine kidney (MDCK) epithelial cells and was displaced from this location upon
      activation of PKC. We defined the basolateral targeting determinant of MacMARCKS
      to be the effector domain, a basic region spanning 24 amino acids and containing
      the PKC phosphorylation sites as well as binding sites for calmodulin and actin.
      This domain, in conjunction with a myristoyl moiety, was sufficient to target a
      non-membrane-associated protein--green fluorescent protein--specifically to the
      basolateral surface of polarized MDCK cells. CONCLUSIONS: This is the first
      description of a specific amino acid sequence that specifies targeting of a
      peripheral membrane protein to the basolateral membrane in polarized epithelial
      cells.

PMID- 9637919
TI  - Translocation of PDK-1 to the plasma membrane is important in allowing PDK-1 to
      activate protein kinase B.
AB  - BACKGROUND: Protein kinase B (PKB) is involved in the regulation of apoptosis,
      protein synthesis and glycogen metabolism in mammalian cells. Phosphoinositide
      dependent protein kinase (PDK-1) activates PKB in a manner dependent on
      phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3), which is also needed
      for the translocation of PKB to the plasma membrane. It has been proposed that
      the amount of PKB activated is determined exclusively as a result of its
      translocation, and that a constitutively active pool of membrane-associated PDK-1
      simply phosphorylates all the PKB made available. Here, we have investigated the
      effects of membrane localisation of PDK-1 on PKB activation. RESULTS: Ectopically
      expressed PDK-1 translocated to the plasma membrane in response to platelet
      derived growth factor (PDGF) and translocation was sensitive to wortmannin, an
      inhibitor of phosphoinositide 3-kinase. Translocation of PDK-1 also occurred upon
      its co-expression with constitutively active phosphoinositide 3-kinase, but not
      with an inactive form. Overexpression of PDK-1 enhanced the ability of PDGF to
      activate PKB. PDK-1 disrupted in the pleckstrin homology (PH) domain which did
      not translocate to the membrane did not increase PKB activity in response to
      PDGF, whereas membrane-targeted PDK-1 activated PKB to the extent that it could
      not be activated further by PDGF. CONCLUSIONS: In response to PDGF, binding of
      Ptdlns (3,4,5)P3 and/or Ptdlns(3,4)P2 to the PH domain of PDK-1 causes its
      translocation to the plasma membrane where it co-localises with PKB,
      significantly contributing to the scale of PKB activation.

PMID- 9637920
TI  - Imaging the spatial dynamics of calmodulin activation during mitosis.
AB  - BACKGROUND: Calcium is an important and ubiquitous signalling ion. In most cell
      types, changes in intracellular calcium concentrations are sensed by calmodulin,
      a signal transduction protein that regulates cell function through its
      interactions with kinases and phosphatases. Calcium signals show complex
      spatiotemporal patterning, but little, if anything, is known about the patterns
      of calmodulin activation inside cells. RESULTS: We have measured calmodulin
      activation continuously during mitosis in living cells with a new probe, a
      fluorescent adduct of calmodulin termed TA-calmodulin. We found that calmodulin
      was activated locally and episodically in the nucleus and mitotic spindle. The
      pattern of calmodulin activation was different from the pattern of calcium
      signals and could not be predicted from the pattern of calcium increase.
      Calmodulin activation was essential for mitotic progression: both entry into
      mitosis and exit from mitosis were blocked by a novel peptide that bound to
      calmodulin with high affinity and so prevented the interaction of calmodulin with
      its target proteins. CONCLUSIONS: These data suggest that calmodulin regulates
      mitotic transitions and demonstrate the utility of fluorescent adducts for
      studying protein activation in living cells with good temporal and spatial
      resolution.

PMID- 9637921
TI  - Thymic skewing of the CD4/CD8 ratio maps with the T-cell receptor alpha-chain
      locus.
AB  - The thymic preference for CD4+ T cells over CD8+ T cells is often attributed to a
      default pathway favouring CD4+ T cells or to homeostatic mechanisms. It is also
      clear, however, that T-cell receptor (TCR) preferences for major
      histocompatibility complex (MHC) class I versus class II binding will strongly
      influence an individual clone's skewing to the CD4 or CD8 subset. The variable
      region of each TCR alpha chain (V alpha) studied to date is found to be
      overrepresented in either CD4+ or CD8+ cells, suggesting that each V alpha
      element can interact more favourably with either MHC class I or class II
      molecules. Indeed, TCRs appear to have an intrinsic ability to interact with MHC
      molecules, and single amino acid residues present in germline-encoded
      complementarity determining region 1 (CDR1) and CDR2 of the V alpha element can
      be responsible for determining MHC specificity. Interestingly, the degree of
      CD4/CD8 skewing is variable among different mouse strains and in human
      populations. Here, we have shown that polymorphism in CD4/CD8 skewing between B6
      and BALB/c mice is determined by the stem cell genotype and not by environmental
      effects, and that it maps in or near the TCR alpha-chain complex, Tcra. This was
      confirmed by comparing Tcra(b) with Tcra(a) or Tcra(c) haplotypes in congenic
      mice. We propose that the array of V alpha genes in various Tcra haplotypes
      exerts influence over the proportion of CD4 and CD8 subsets generated and may
      account in part for the observed thymic skewing. Thus, while it has been
      suggested that the TCR genes have been selected by evolution for MHC binding, our
      results further indicate selection for class II MHC preference.

PMID- 9637922
TI  - Identification and functional analysis of the ezrin-binding site in the
      hyaluronan receptor, CD44.
AB  - ERM (ezrin, radixin and moesin) proteins function as linkers between the actin
      cytoskeleton and the plasma membrane. In addition to this structural role, these
      proteins are highly regulatable making them ideal candidates to mediate important
      physiological events such as adhesion and membrane morphology and to control
      formation and breakdown of membrane-cytoskeletal junctions. Recently, a direct
      interaction in vitro has been demonstrated between ERM proteins and the
      hyaluronan receptor, CD44. We have mapped the ezrin-binding site to two clusters
      of basic amino acids in a membrane-proximal 9 amino-acid region within the CD44
      cytoplasmic domain. To investigate the functional importance of this interaction
      in vivo, we created a number of mutations within full-length CD44 and expressed
      these mutants in human melanoma cells. We demonstrate here that mutations within
      the ezrin-binding site do not disrupt the plasma membrane localization of CD44
      and, in addition, that this region is not required to mediate efficient
      hyaluronan binding. These studies suggest that ERM proteins mediate the outside
      in, rather than inside-out, signalling of adhesion receptors.

PMID- 9637923
TI  - The thiol oxidoreductase ERp57 is a component of the MHC class I peptide-loading
      complex.
AB  - The proper folding and assembly of major histocompatibility complex (MHC) class I
      molecules in the endoplasmic reticulum (ER) is an intricate process involving a
      number of components. Nascent heavy chains of MHC class I molecules, translocated
      into the ER membrane, are rapidly glycosylated and bind the transmembrane
      chaperone calnexin. In humans, after dissociation from calnexin, fully oxidized
      MHC class I heavy chains associate with beta 2-microglobulin (beta 2m) and the
      soluble chaperone calreticulin. This complex interacts with another transmembrane
      protein, tapasin, which is believed to assist in MHC class I folding as well as
      in mediating the interaction between assembling MHC class I molecules and the
      transporter associated with antigen processing (TAP). The TAP heterodimer (TAP1
      TAP2) introduces the final component of the MHC class I molecule by translocating
      peptides, predominately generated by the proteasome, from the cytosol into the ER
      where they can bind dimers of beta 2M and the MHC class I heavy chain. Recently,
      the thiol oxidoreductase ERp57--also known as GRP58, ERp61, ER60, Q2, HIP-70, and
      CPT and first misidentified as phospholipase C-alpha--has been shown to bind in
      conjunction with calnexin or calreticulin to a number of newly synthesized ER
      glycoproteins when their N-linked glycans are trimmed by glucosidases I and II.
      It was speculated that ERp57 is a generic component of the glycan-dependent ER
      quality control system. Here, we show that ERp57 is a component of the MHC class
      I peptide-loading complex. ERp57 might influence the folding of MHC class I
      molecules at a critical step in peptide loading.

PMID- 9637924
TI  - A role for the thiol-dependent reductase ERp57 in the assembly of MHC class I
      molecules.
AB  - An important mammalian defence strategy against intracellular pathogens is the
      presentation of cytoplasmically derived short peptides by major
      histocompatibility complex (MHC) class I molecules to cytotoxic T lymphocytes.
      MHC class I molecules assemble in the endoplasmic reticulum (ER) with chaperones,
      including calnexin and calreticulin, before binding to the transporter associated
      with antigen processing (TAP). We show here that the thiol-dependent reductase
      ERp57 (also known as ER60 protease) is involved in MHC class I assembly. ERp57 co
      purified with the rat TAP complex (comprising TAP1 and TAP2), and associated with
      MHC class I molecules at an early stage in their biosynthesis. This association
      was sensitive to castanospermine, which inhibits the processing of glycoproteins.
      Human MHC class I molecules were also found to associate with ERp57. We conclude
      that ERp57 is a newly identified component of the MHC class I pathway, and that
      it appears to interact with MHC class I molecules before they associate with TAP.

PMID- 9637925
TI  - Evidence for successive peptide binding and quality control stages during MHC
      class I assembly.
AB  - Intracellular antigens are continually presented to cytotoxic T lymphocytes by
      major histocompatibility complex (MHC) class I molecules, which consist of a
      polymorphic 43 kDa heavy chain and a 12 kDa soluble subunit beta 2-microglobulin
      (beta 2m), and which bind an 8-10 amino-acid antigenic peptide. The assembly of
      this trimolecular complex takes place in the lumen of the endoplasmic reticulum
      (ER) and almost certainly requires cofactors. Most MHC class I molecules in the
      ER that have not yet acquired peptide are simultaneously bound to the transporter
      associated with antigen processing (TAP), to the 48 kDa glycoprotein tapasin and
      to the lectin-like chaperone calreticulin, in a multicomponent 'loading complex'.
      Previous studies have shown that a mutant MHC class I molecule T134K (in which
      Thr134 was changed to Lys) fails to bind to TAP. Here, we show that this point
      mutation also disrupted, directly or indirectly, the interaction between MHC
      class I molecules and calreticulin. T134K molecules did not present viral
      antigens to T cells even though they bound peptide and beta 2m normally in vitro.
      They exited the ER rapidly as 'empty' MHC class I complexes, unlike empty wild
      type molecules which are retained in the ER and degraded. We show here that,
      paradoxically, the rapid exit of empty T134K molecules from the ER was dependent
      on a TAP-derived supply of peptides. This implies that MHC class I assembly is a
      two-stage process: initial binding of suboptimal peptides is followed by peptide
      optimisation that depends on temporary ER retention.

PMID- 9637926
TI  - EGF induces recycling membrane to form ruffles.
AB  - KB cells are know to respond to epidermal growth factor (EGF) by producing
      prodigious ruffles in the plasma membrane within minutes. The signal transduction
      pathway underlying this effect in fibroblasts is mediated through Rac, a member
      of the Ras-like family of GTPases. As ruffles are rich in components of the
      cytoskeleton--particularly in actin and ezrin--it has been suggested that ruffles
      arise when activated Rac modulates the actin cytoskeleton to push out a membrane
      protrusion. We set out to see whether the surface of new ruffles arises from
      neighbouring membrane, or whether it comes from an intracellular pool of
      endocytosed membrane. If it arose by exocytosis from endosomes, it would be
      expected to be enriched in those recycling receptors that are concentrated in
      coated pits in the endocytic side of the cycle. On the other hand, if it arose
      passively from the adjacent plasma membrane, a uniform distribution of these
      receptors would be expected. Here, we show that as soon as ruffles appear on KB
      cells in response to EGF, their membrane surfaces are enriched in both
      transferrin and low density lipoprotein (LDL) receptors. Both these proteins are
      known to be selectively concentrated into endosomal membranes by clathrin
      mediated endocytosis. Our results reveal that the surfaces of ruffles arise by
      exocytosis of internal membrane from the endocytic cycle and, therefore, that a
      primary action of Rac is to redirect the exocytosis of recycling membrane into
      just those specific sites where ruffles form.

PMID- 9637927
TI  - Formation of RuvABC-Holliday junction complexes in vitro.
AB  - In Escherichia coli, the RuvA, RuvB and RuvC proteins are required for the late
      stages of homologous recombination and DNA repair. RuvA and RuvB form a complex
      that interacts with Holliday junctions--crossed DNA structures that are
      recombination intermediates--and promotes branch migration; RuvC is a junction
      specific endonuclease that resolves Holliday junctions and completes the
      recombination process. Because genetic and biochemical experiments suggest that
      the processes of branch migration and resolution are linked,
      coimmunoprecipitation experiments were carried out to determine whether the three
      Ruv proteins interact to form a functional complex (RuvABC). Using a synthetic
      Holliday junction, a multisubunit complex containing the junction and RuvA, RuvB
      and RuvC was detected. In the absence of RuvB, RuvAC-junction complexes were
      observed. Complex formation was not facilitated by duplex DNA. The identification
      of a RuvABC-junction complex provides direct evidence that the RuvABC proteins
      interact at the Holliday junction.

PMID- 9637928
TI  - Genetic advances in cystic fibrosis: to screen, to treat or both?
AB  - Since the identification of the cystic fibrosis (CF) gene in 1989 there have been
      considerable advances in treatment and fierce debate concerning CF screening
      programmes. Cystic fibrosis imposes a burden of suffering, of onerous treatment
      and of reduced lifespan. New emerging treatments are very expensive but are
      expected to improve survival and quality of life. Treatments and screening
      programmes should not be played off against one another in choices for funding.
      This paper presents an argument for the appropriate use of newer treatments which
      could be funded from savings arising from the effects of widespread
      implementation of newborn and active cascade carrier detection programmes.
      Newborn screening delays the need for expensive treatments reserved for those
      with advanced disease, by reducing pre-diagnosis tissue damage and the rate of
      progression of the disease. Carrier screening has the capacity to decrease the
      numerical burden of affected children born and increases the number of children
      born free of disease. For the present, carrier screening in the absence of a
      family history could be funded by the individuals who wish it or by those
      prepared to buy this service. All types of screening presume quality control, an
      existing laboratory and counselling infrastructure and an established method of
      communicating results.

PMID- 9637929
TI  - Transition from paediatric to adult-orientated care for adolescents with cystic
      fibrosis.
AB  - Adolescence is a time of major physical and psychological change. Young teenagers
      need to become comfortable with their developing sexuality, to begin moving
      towards independence with a greater reliance on peer group acceptance, to face
      the future and to make important decisions about their education, career and
      goals. Difficulties inherent in all of these steps to adult life are magnified by
      chronic ill health. It is harder for adolescent patients to break family ties,
      harder to feel accepted by their peer group, harder to plan realistically for the
      future. It must be the overriding aim of the professional health carers to
      encourage these patients to confront the problems of adolescence and to help them
      maintain their physical and emotional stability throughout this challenging
      period. Parents also must be supported, and encouraged gradually to devolve to
      their child responsibilities for decision making and for taking prescribed
      medication. A planned and sensitive transition from a paediatric to an adult
      health-care system will aid a successful evolution to an independent adult life.
      The paediatric hospital environment is not best equipped to deal with the
      problems of adolescence. Just as parents must allow their child to move on, so
      the paediatric caring team must loosen its ties with the patient and allow
      transfer to the adult team. There are several ways of effecting this transfer of
      care. None of them is proven to be better than any other, but the transfer should
      always be planned, smooth, efficient and expected by the patient. Ideally, all
      patients should have the opportunity to transfer to a properly equipped and
      properly staffed adult cystic fibrosis centre where they can continue to receive
      the highest standards of care from an experienced multidisciplinary team.

PMID- 9637930
TI  - The management of young adults with cystic fibrosis: 'genes, jeans and genies'.
AB  - Cystic fibrosis is now an adult disease. The understanding of the basic
      pathophysiology of this disease has increased considerably over the past decade.
      This has resulted in effective management protocols and the development of
      innovative approaches to therapy. Management of young adults is complex and
      requires expert medical care delivered in a sensitive and appropriate way. The
      daily treatment schedule for many adults involves physiotherapy; nebulized, oral
      and i.v. drugs; exercise and nutritional supplements. Adherence to such treatment
      while living a busy school, work and social life is extremely difficult for
      patients. The psychological implications of having a disease with very
      significant morbidity and mortality also has an enormous impact on individuals
      with CF. Many of these issues have evolved as survival has increased and the next
      few decades may produce more unexpected 'genies'. These may be from the disease
      itself or from some of the exciting new treatments currently being developed. It
      is important that individuals with CF are fully involved in decisions relating to
      their treatment and that CF teams provide optimal and appropriate care to enable
      these young adults to enjoy their lives to the fullest extent.

PMID- 9637931
TI  - Nutritional management in cystic fibrosis--an alternative perspective in
      gastrointestinal function.
AB  - The gastrointestinal problems in cystic fibrosis (CF) may limit energy and
      nutrient availability and also cause symptoms such as abdominal pain and
      disturbed bowel habit which may further suppress appetite or alter the diet.
      Taken together this may lead to an inadequate supply of energy and nutrients to
      meet the nutritional requirements of the individual resulting in restricted
      growth or weight loss. A failure to optimize the digestive and absorptive
      capacity of the gastrointestinal tract places greater emphasis upon nutritional
      management by food intake alone. Practitioners need to focus more on
      gastrointestinal dysfunction in CF and its impact upon food intake in order to
      improve the efficacy of nutritional management. Refined stable isotopic tracers
      allow further exploration of the pathophysiology of the gastrointestinal tract in
      terms of nutrient availability. In clinical practice, a closer assessment of
      gastrointestinal function is supported by the use of simple, noninvasive tools
      which, both objectively and systematically, characterize those patients who have
      problems.

PMID- 9637932
TI  - Finding evidence to support airway clearance techniques in cystic fibrosis.
AB  - Chest physiotherapy, aiming to clear bronchopulmonary secretions, has become a
      mainstay in the respiratory management of cystic fibrosis (CF). Early diagnosis
      and new therapeutic interventions have dramatically improved the outlook for
      patients with this disorder and it is no longer a disease of childhood. Along
      with these changes chest physiotherapy has also progressed, with the development
      of several treatment modalities that are more effective and can be performed by
      the patient without assistance. This allows older children and adults with CF to
      lead more normal and independent lifestyles. Despite this progress questions
      remain regarding the efficacy and consequences of airway clearance techniques,
      the scientific evidence available to support the selection of the most
      appropriate treatment modality and, not least, the problems associated with the
      treatment-related burden that is placed on patients and their families.

PMID- 9637933
TI  - Exercise limitations and training for patients with cystic fibrosis.
AB  - Exercise has much to offer to cystic fibrosis patients. Overcoming the limits of
      decreased pulmonary function by increasing fitness has a considerable potential
      to improve patients' quality of life; decreased breathlessness allows greater
      mobility and participation with peers in social and sporting activities, improves
      confidence and self-esteem and creates a greater pleasure in life for the
      individual patient. There are also immediate therapeutic gains and potentially
      long-term gains with improved survival. Above all, cystic fibrosis patients enjoy
      and prefer exercise as a therapeutic option to most other forms of therapy.

PMID- 9637934
TI  - Community-based care in cystic fibrosis: role of the cystic fibrosis nurse
      specialist and implications for patients and families.
AB  - Improved survival for cystic fibrosis has rapidly increased over the past four
      decades, with patients now living well into adult life. With changes in the
      structure of the National Health Service and the formation of provider units and
      general practitioner (GP) fund-holding practices, it is important to strengthen
      links between the hospital and community teams to ensure that the CF patient
      receives adequate care. Increasingly, treatment is being carried out at home, and
      this emphasis on home-based therapy demands that parents/carers and patients must
      acquire the skills and knowledge of complex therapies in order to optimize
      health. It is the role of the CF nurse specialist (NS) to educate those who will
      deliver the care, co-ordinate the provision of services at home, liaise with the
      CF team and community health-care professionals and to support the patient and
      their carers.

PMID- 9637935
TI  - Contemporary psychosocial issues in cystic fibrosis: treatment adherence and
      quality of life.
AB  - This review focuses on the two major psychosocial areas currently topical in
      cystic fibrosis research: treatment adherence and quality of life. First, the
      paper discusses the importance of evaluating adherence to treatments and medical
      advice, its measurement, predictors of adherence and non-adherence and whether
      the data should be used to inform clinical practice and policy decisions. Second,
      the purpose of evaluating quality of life in cystic fibrosis and an overview of
      the data are discussed. Both areas have suffered from problems with terminology
      and definition, inappropriate methodologies and hence difficulties with data
      interpretation. Future directions for research are advocated.

PMID- 9637936
TI  - It's not football.
AB  - Today I am as happy as I could ever be. I have created a lot out of very little,
      I have worked full time, played full time, got full-time friends, full-time
      independence, had full-time love and am lucky enough to be with my new full-time
      love who helps me a great deal both physically and mentally. It is definitely no
      fun coughing until your chest is sore in the morning, afternoon and evening.
      Having wringing night-sweats from cepacia. Wanting to sleep more than Mr Sleep
      from Sleepland. Taking tablets the size of which sunk the Belgrano. Finding time
      for physiotherapy, eating the right meals, playing on my Playstation. Depression
      has got through on previous occasions, but not for long, and it has never
      resulted in anything more than a 'wake up and smell the coffee' call from myself.
      Having CF is no ball game (otherwise it would be called football or something!),
      but I have had a lot of fun and will continue to do so for however long. Two
      years, five years, 20 years--who's to say, not me. We could all have the same
      left, I just hope that everyone has as much fun.

PMID- 9637937
TI  - Neurophysiological study in an Italian family with autosomal dominant late-onset
      leukodystrophy.
AB  - Evoked potentials (EPs) and nerve conduction velocities (NCV) were evaluated in 8
      affected and 10 asymptomatic members of a new Italian family with an adult-onset
      autosomal dominant leukodystrophy of uncertain nosography. NCV studies did not
      show anomalies. Various EPs abnormalities were found in all the symptomatic
      patients (increase of interpeak latency and/or loss of cortical responses),
      according with a myelin disorder. Among the asymptomatic subjects 3/10 (30%)
      showed similar anomalies at auditory brainstem EPs (increase of I-III/I-V/III-V
      interval). Two of these patients had normal brain MRI. This datum require further
      confirms (very low penetrance of the disease?), but it remarks the importance of
      a functional study of SNC in order to obtain elements not usually given from
      clinical and neuroradiological study.

PMID- 9637938
TI  - Cerebral potentials are not evoked by activation of Golgi tendon organ afferents
      in human abductor hallucis muscle.
AB  - The earliest components of the somatosensory evoked potentials (SSEP) are
      generated by excitation of the fastest low-threshold, thick myelinated group I
      afferents. Ib afferents belonging to this group innervate Golgi tendon organs and
      are excited almost selectively by a muscle twitch. Contraction of the abductor
      hallucis muscle was evoked by intramuscularly placed teflon insulated needle
      electrodes in ten healthy volunteers. We failed to demonstrate any cortical
      activity (over Cz' vs. Fz) following isolated muscle contractions. Our results do
      not point to a significant projection of group Ib afferents to the human
      somatosensory cortex at least with the small numbers of fibers activated by
      intramuscular stimulation of abductor hallucis muscle.

PMID- 9637939
TI  - Activation and suppression of the trapezius muscle induced by transcranial
      magnetic stimulation.
AB  - Motor evoked potentials (MEPs) and silent periods (SPs) in the trapezius muscle
      induced by transcranial magnetic stimulation (TMS) were investigated in 15
      healthy subjects. Stimuli were applied with a Novametrix Magnetic stimulator
      using a 14 cm circular coil 4 cm lateral to the vertex on the biauricular line.
      Surface electrodes were used for simultaneous bilateral electromyographic
      recordings of the trapezius. TMS invariably induced contralateral MEPs (latency
      10.5 +/- 1.3 ms, mean +/- SD), with ipsilateral responses in 53% of the subjects
      (latency 11.1 +/- 2.5 ms). The mean duration of the SPs was approximately 90 ms
      on both sides. There were no significant side differences between any of the MEP
      or SP parameters. To study the influence of subcortical inhibition phenomena TMS
      induced responses were assessed following electrical mental nerve stimulation
      with interstimulus intervals (ISI) of 0-100 ms. MEP latencies significantly
      increased at ISI of 10-100 ms, whereas MEP amplitudes and SPs did not change.
      These findings may reflect a trigeminal induced exteroceptive suppression of
      trapezius muscle activity.

PMID- 9637940
TI  - Masseter reflex potentials in olivo-ponto-cerebellar atrophy.
AB  - We recorded masseter reflex potentials to examine the correlation between the
      masseter reflex and the muscle stretch reflexes of limbs in 19 patients with
      olivo-ponto-cerebellar atrophy (OPCA). The patients were subdivided into hyper-
      (n = 5), normo- (n = 7) and hypo- (n = 7) reflexia groups according to the
      degrees of the conventional deep tendon jerks in the upper limbs. The masseter
      reflex potentials, elicited by tapping the chin with a reflex hammer, were
      recorded from the bilateral masseters using a pair of surface electrodes. The
      latency of the potentials in the hyporeflexia was significantly longer than in
      the other groups, while the amplitude of those in the hyperreflexia group was
      significantly higher than in the other groups. These results indicate that in
      patients with OPCA the magnitude and latency of the masseter reflex correlates
      with the status of the muscle stretch reflexes of the limbs in contrast with
      Friedreich's ataxia where the masseter reflex has been reported to be normal or
      hyperactive despite hyporeflexia in the limbs.

PMID- 9637941
TI  - Suprascapular nerve conduction: a comparative analysis in normal subjects.
AB  - An electromyographic examination is often utilized to confirm the diagnosis of
      suprascapular neuropathy in patients with shoulder pain and dysfunction. The
      purpose of this study was to compare three compound motor action potential (CMAP)
      recording methods (surface electrode, monopolar needle, concentric needle) for
      evaluating suprascapular nerve conduction. Twenty-two normal, healthy subjects
      were tested with each method. Differences between the recording methods were
      noted for CMAP latencies and amplitudes with the monopolar needle recordings
      having the shortest mean latency and greatest mean amplitude. The monopolar
      needle recordings also appeared to give a more reproducible measurement of CMAP
      latency and evoked amplitude to the supraspinatus and infraspinatus. Therefore,
      it may be more accurate to use a monopolar needle to record suprascapular nerve
      conduction and determine abnormalities with a side-to-side latency difference of
      0.4 ms being acceptable. Considering the diverse branching of the suprascapular
      nerve, and the monopolar needle's relatively small sampling area of motor fibers,
      it may be prudent to test conduction to multiple sites within these muscles for
      the most accurate assessment.

PMID- 9637942
TI  - Detection of nerve entrapment during limb lengthening by means of near-nerve
      recording.
AB  - Eight patients undergoing limb lengthening by the Ilizarov method had near-nerve
      needle electrode conduction studies when they developed clinical signs of nerve
      entrapment. The near-nerve technique was chosen because it is highly sensitive to
      configurational changes which appear in the action potential as injury occurs. In
      10 out of 13 symptomatic limbs the near-nerve potential was found to be
      abnormally small and its usually smooth contour had become notched and irregular.
      In the remaining 3 limbs the potentials were normal initially but became abnormal
      as further constriction of the nerve took place. Nerve potentials remained normal
      in size and shape in asymptomatic limbs undergoing lengthening and were not
      altered by application of the Ilizarov frames themselves. The near-nerve
      technique proved useful in the early detection of nerve injury in these patients
      and thus enabled surgical intervention before nerve damage had become permanent.

PMID- 9637943
TI  - Ratios of nerve conduction parameters in proximal to distal limbs remain constant
      through the second to the eighth decades.
AB  - We investigated the effect of age on nerve conduction parameters to establish a
      diagnostic validity in demyelinating neuropathies of the aged. We evaluated 257
      subjects (age 10-76 years old) with no history or signs of peripheral
      neuropathies. The CMAP amplitude ratio (proximal CMAP/distal CMAP), duration
      ratio, and area ratio were almost the same throughout the second to eighth
      decades. The respective lower limits of the normal CMAP amplitude ratio (mean-3
      SD) were 0.79 (median nerve), 0.75 (ulnar nerve), 0.57 (peroneal nerve), and 0.45
      (tibial nerve). The upper limits of the normal CMAP duration ratio (mean +3 SD)
      were 1.21 (median nerve), 1.22 (ulnar nerve), 1.37 (peroneal nerve), and 1.35
      (tibial nerve). The lower limits of the normal CMAP area ratio (mean-3 SD) were
      0.81 (median nerve), 0.78 (ulnar nerve), 0.60 (peroneal nerve), and 0.57 (tibial
      nerve). No age-related changes were observed in the amplitude ratio or duration
      ratio SNAP, although the standard deviation increased with age. Since the
      amplitude, duration and area ratios are easily calculated and age-independent,
      they can provide useful and reliable information on aged patients with
      demyelinating neuropathies by conventional nerve conduction studies.

PMID- 9637944
TI  - Neurophysiological studies in herpes simplex encephalitis.
AB  - In herpes simplex encephalitis (HSE), simultaneous electro-encephalogram (EEG)
      and evoked potential studies have not been reported, although EEG changes have
      been described. In this communication, EEG, somatosensory and motor evoked
      potentials have been reported in 9 patients with HSE. The patients' age ranged
      between 2 and 70 years and 3 were females. Seven patients had seizures, CT scan
      was abnormal in 6 and MRI in remaining 3 patients. Seven patients received
      acyclovir therapy; one patient died and 6 had poor outcome. The initial EEG was
      carried out within 5 days of ictus and was abnormal in all the patients. The EEG
      abnormalities included frontotemporal delta slowing in 5, periodic lateralised
      epileptiform discharge in 3, runs of spike and periodic activity in one patient
      each. At 3 months, EEG was normal in 6 patients but it did not correlate with
      clinical recovery. Central motor conduction time (CMCT) to upper limb and median
      somatosensory evoked potential (SEP) were normal in all. CMCT to lower limbs and
      tibial SEPs were unrecordable in one patient who had wide spread herpes simplex
      virus (HSV-1) infection associated with AIDS, and died on 18th day of illness.
      From this study, we conclude that EEG although is frequently abnormal and may
      provide useful diagnostic information in a setting of encephalitis but evoked
      potential changes are infrequent; and if present an association of HIV infection
      should be considered.

PMID- 9637945
TI  - Differential diagnosis of chronic idiopathic polymyositis and neuromyositis.
AB  - The term neuromyositis indicates a very rare type of polymyositis where, beside
      the usual muscular manifestations, there are signs of peripheral neuropathy.
      Although a lot of patients with neuromyositis has been published, it is a very
      controversial entity. There may be considerable difficulty in distinguishing
      chronic polymyositis from neuromyositis, even with the aid of electromyographic
      and muscle biopsy examinations. The aim of this investigation was to re-establish
      the clues for distinguishing chronic polymyositis from neuromyositis. Fifty-seven
      patients took part in this investigation. They were subdivided into two groups
      according to EMG and muscle biopsy data. First group consisted of 29 patients
      with chronic polymyositis and second group consisted of 28 patients with chronic
      neuromyositis. Our data confirm the existence of neuromyositis as an entity with
      different clinical, electromyographic and biopsy findings than polymyositis. The
      differentiation between chronic polymyositis and neuromyositis is a difficult
      task on purely clinical ground. Electromyographic recordings with widespread
      myopathic features, some large potentials and spontaneous activity could be found
      in both diseases. The most common and important electromyographic findings in
      patients with neuromyositis are prolonged sensory and motor nerve conduction
      velocities. In conclusion electromyography and muscle biopsy may be useful in the
      differential diagnosis of polymyositis and neuromyositis.

PMID- 9637946
TI  - The muscle inhibitory period by transcranial magnetic stimulation. Study in
      stroke patients.
AB  - Motor evoked potentials (MEPs) elicited over hand muscles by transcranial
      magnetic stimulation (TMS) were studied in healthy individuals and, bilaterally,
      in patients with cerebral infarction. Conduction time of the central motor
      pathways (CMCT), threshold intensity, and amplitude of the MEPs were correlated
      with recovery motor hand function after stroke. Following MEPs by TMS during
      tonic muscle contraction, there is a transient suppression of muscle action. This
      inhibitory period (IP) was significantly shorter in the upper paretic limb of
      stroke patients with spasticity than in normal limb of the patients and healthy
      individuals. Shortening of the IP duration was correlated to degree of upper limb
      spasticity (Ashworth scale) and may be due to supraspinal level reduction of the
      inhibitory function. The IP study contributes to a better quantification of the
      hand function in stroke patients.

PMID- 9637947
TI  - Can adults adequately convert alpha-linolenic acid (18:3n-3) to eicosapentaenoic
      acid (20:5n-3) and docosahexaenoic acid (22:6n-3)?
AB  - A diet including 2-3 portions of fatty fish per week, which corresponds to the
      intake of 1.25 g EPA (20:5n-3) + DHA (22:6n-3) per day, has been officially
      recommended on the basis of epidemiological findings showing a beneficial role of
      these n-3 long-chain PUFA in the prevention of cardiovascular and inflammatory
      diseases. The parent fatty acid ALA (18:3n-3), found in vegetable oils such as
      flaxseed or rapeseed oil, is used by the human organism partly as a source of
      energy, partly as a precursor of the metabolites, but the degree of conversion
      appears to be unreliable and restricted. More specifically, most studies in
      humans have shown that whereas a certain, though restricted, conversion of high
      doses of ALA to EPA occurs, conversion to DHA is severely restricted. The use of
      ALA labelled with radioisotopes suggested that with a background diet high in
      saturated fat conversion to long-chain metabolites is approximately 6% for EPA
      and 3.8% for DHA. With a diet rich in n-6 PUFA, conversion is reduced by 40 to
      50%. It is thus reasonable to observe an n-6/n-3 PUFA ratio not exceeding 4-6.
      Restricted conversion to DHA may be critical since evidence has been increasing
      that this long-chain metabolite has an autonomous function, e.g. in the brain,
      retina and spermatozoa where it is the most prominent fatty acid. In neonates
      deficiency is associated with visual impairment, abnormalities in the
      electroretinogram and delayed cognitive development. In adults the potential role
      of DHA in neurological function still needs to be investigated in depth.
      Regarding cardiovascular risk factors DHA has been shown to reduce triglyceride
      concentrations. These findings indicate that future attention will have to focus
      on the adequate provision of DHA which can reliably be achieved only with the
      supply of the preformed long-chain metabolite.

PMID- 9637948
TI  - Radical oxidation of riboflavin.
AB  - Riboflavin, lumiflavin and lumichrome were produced by light catalysis and gamma
      irradiation. Their formation under various conditions was determined, and a
      number of intermediates identified. Fluorescence excitation and emission spectra
      were determined for the compounds and compared with the absorbency spectra. While
      lumiflavin predominated in alkali and lumichrome in neutral solutions in the
      light-catalyzed reaction, all products were produced to some extent under all
      conditions. Gamma radiation resulted only in the formation of lumichrome, with no
      observable intermediates.

PMID- 9637949
TI  - delta-Aminolevulinate dehydratase inhibition by ascorbic acid is mediated by an
      oxidation system existing in the hepatic supernatant.
AB  - The effect of ascorbic acid (AA) on hepatic delta-aminolevulinic acid dehydratase
      (ALA-D) activity was studied. AA decreased enzyme activity by reducing maximum
      velocity and tended to increase the Michaelis constant. ALA-D inactivation by AA
      occurred similarly both in air and argonium atmosphere incubation. DTT reduced
      considerably the inhibitory effect of AA on ALA-D, but glutathione was
      ineffective in reversing inactivation. These data indicate that inhibition occurs
      mainly due to an acceleration of the oxidation rate mediated by the hepatic
      supernatant utilizing AA in sulfhydryl groups of cysteine residues present at the
      ALA-D active site. AA probably acts on cysteine from the ALA-D B site since
      cucumber and radish leaves ALA-D was not inhibited by AA (up to 16 mM). The
      addition of free radical scavengers to the medium did not alter ALA-D
      inactivation caused by AA, indicating that active oxygen species formed during AA
      oxidation were not directly related to -SH oxidation. The chelation of zinc ions
      from the enzyme by EDTA turned ALA-D more susceptible to the inhibitory effect of
      AA. This effect seems to involve mainly ZnB, which is known to bind to four
      cysteines. The present data suggest that AA may participate in the regulation of
      the heme biosynthesis pathway by promoting a reversible inactivation of ALA-D.

PMID- 9637950
TI  - Usefulness of the prognostic inflammatory and nutritional index (PINI) in
      hospitalized elderly patients.
AB  - The prognostic inflammatory and nutritional index (PINI) is a simple scoring
      system of overall health which aggregates two blood markers of inflammatory (C
      reactive protein and alpha(1)-acid glycoprotein) and of nutritional (albumin and
      transthyretin) states. This study was undertaken with a view to evaluate, in
      comparison to currently used predictive approaches, the potential usefulness of
      PINI to forecast hospital mortality and outcome of patients hospitalized in an
      acute geriatric unit. 1,066 elderly patients, aged 82.7 +/- 6.6 years and
      fulfilling inclusion criteria, were enrolled in the study. Logistic regression
      analysis and calculation of relative risk (RR) were carried out for
      epidemiological data with a cut-off value of 25 for PINI. Immediate mortality
      (7.9%) of admissions) was predicted by PINI > or = 25 (RR = 4.34). Only 387
      patients (36.3%) could rejoin their residence location (home or family). A
      sizeable proportion of acute patients (55.8%) failed to recover and/or developed
      diseased states requiring chronic care management. Incapacity to return home was
      predicted by PINI > or = 25 (RR = 2.04). Hypoalbuminaemia < or = 30 g/L was not
      found a predictor of mortality but was associated with total disability (RR =
      9.08). The optimal PINI cut-off value to predict mortality was calculated at 8.8
      using the ROC analytic approach. We conclude that the PINI formula is helpful to
      predict both nearest lethality and chronic institutionalization. This scoring
      system should take a place within the battery of tests used to identify and to
      follow up acutely ill elderly patients at risk of major complications.

PMID- 9637951
TI  - Nutritional status and serum lipids of a rural population in Northeast Thailand-
      an example of health transition.
AB  - An investigation was undertaken in Northeast Thailand, a country undergoing rapid
      health transition, to find out whether there is a likelihood that the nutritional
      and lipid pattern of an adult population in Northeast Thailand is related to
      coronary heart disease in the same way as in western countries. In a cross
      sectional study, the body mass index (BMI) and the waist-hip ratio as well as the
      important plasma lipids were determined. The nutritional status and the lipid
      profile of the predominantly middle-aged population is characterised by a
      generally favourable nutritional status and lipid concentrations, where the
      distribution, indicated by the medians, of the relevant variables over the total
      population is concerned. A rather high proportion of individuals was found to be
      overnourished and to have high triglyceride levels. Individuals with high
      triglyceride levels run a risk of developing coronary heart disease only when the
      LDL-HDL fraction is above 5. Only 3% of the total population investigated had a
      LDL-HDL ratio above that value. Since hypertriglyceridaemia is also linked to the
      insulin-resistant syndrome, it is concluded that, if the mortality of coronary
      heart disease increases in future, then this must be accounted probably more to
      the after-effects of the insulin-resistant syndrome than to the direct effect of
      an atherogenic lipid pattern. This view is supported by a high prevalence of
      impaired glucose tolerance (IGT) and non-insulin dependent diabetes mellitus
      (NIDDM) in the population under survey. Preventive measures in the area should
      concentrate among others on reducing overnutrition, especially among women, and
      increasing physical activity and screening for NIDDM.

PMID- 9637952
TI  - Nutritional and psychological status of young women after a short-term use of a
      triphasic contraceptive steroid preparation.
AB  - The present study was aimed to assess the psychological status of young healthy
      women after the administration of a triphasic contraceptive steroid preparation
      for six complete menstrual cycles. Subjects had never used oral contraceptives
      (OC) and had neither a familial history of depression nor psychological
      disturbances. OC-induced psychological disturbances were interpreted for years as
      evidence of pyridoxine (vitamin B6) deficiency. Other nutritional deficiencies,
      namely in cobalamin, folate and iron, can disturb the functioning of the central
      nervous system. In addition, a deficiency of any of these nutrients can lead to
      several anemia-induced symptoms that are highly susceptible to influence the
      psychological status. For ample evidence, nutritional status was then evaluated
      in parallel to psychological testing. Blood iron and vitamin levels of interest
      were found to be adequate and could not have biased the response to a
      psychological test (MMPI). This study showed that a 6-month Triphasil treatment
      did not modify significantly the psychological status of subjects. To our
      knowledge, this is the first psychological study on young never OC-users taking
      an identical triphasic contraceptive steroid preparation to investigate early
      psychological side-effects due to OC, at a similar time of the menstrual cycle,
      when nutritional status was also evaluated.

PMID- 9637953
TI  - Effects of feeding fresh garlic and garlic oil on detoxifying enzymes and
      micronuclei formation in rats treated with azoxymethane.
AB  - The effect of feeding a fresh garlic or garlic oil-supplemented diet was studied
      in rats for a period of 23 weeks with or without the treatment of a carcinogen
      azoxymethane (AOM), on the modulation of detoxification enzymes and micronuclei
      formation. The results showed that feeding fresh garlic or garlic oil
      supplemented diets tended to reduce hepatic lipid peroxidation, though not to
      significant levels. Glutathione content was also not altered. The catalase
      activity in liver of rats fed a fresh garlic-supplemented diet was reduced
      compared to that of the control diet; however, the activity was not affected by
      AOM treatment. Ingestion of garlic caused a 40 percent increase in the hepatic
      glutathione peroxidase activity, whereas carcinogen treatment reduced it. The
      activity of hepatic glutathione-S-transferase was unaffected by the feeding
      regimen, while it was lowered in the garlic oil diet group treated with AOM. The
      gamma glutamyl transpeptidase activity was elevated more than sevenfold, in the
      kidney of rats treated with AOM, while it was reduced almost to half when the AOM
      treated rats were fed fresh garlic or garlic oil. Micronuclei formation was
      increased fourfold, in rats exposed to AOM whereas the increase was reduced to
      half when AOM-injected groups had either fresh garlic or garlic oil in their
      diet. From these studies, it is concluded that long-term feeding of garlic, fresh
      or oil, reduced the toxic effect of AOM in rats.

PMID- 9637954
TI  - Cardiovascular disease myths and facts.
AB  - Myths about cardiovascular disease--that the problem is going away, that it is a
      "good" way to die, and that no further research is needed--are undermining
      prevention efforts and funding for research. Physicians need to counteract these
      myths.

PMID- 9637955
TI  - Kuru and mad cow disease: understanding the prion theory.
AB  - A preponderance of evidence indicates that several neurodegenerative disorders
      are caused by prions: abnormally folded proteins that can induce abnormal folding
      in other normal protein molecules. Further, these "infections" can cross some
      species barriers.

PMID- 9637956
TI  - The hospitalist: will inpatient specialists improve care?
AB  - The number of hospitalists--i.e., practitioners who specialize in the care of
      hospital inpatients--is growing rapidly in the United States. In part a response
      to managed care's push for better health outcomes with a minimum waste of time,
      effort, and money, this new specialty has its own national organization,
      affiliated with the American College of Physicians. Challenges to hospitalists
      include minimizing the use of consultations and unnecessary laboratory tests for
      inpatient care, and ensuring continuity of care once patients leave the hospital.

PMID- 9637957
TI  - Sildenafil (Viagra) for treating male erectile dysfunction.
AB  - Sildenafil, the first oral drug for treating male erectile dysfunction, appears
      effective and well tolerated. However, more time and experience will be needed to
      establish this drug's true efficacy and safety.

PMID- 9637958
TI  - Infectious disease and transplantation: messages for the generalist.
AB  - Today, more patients than ever are receiving organ or bone marrow transplants and
      are surviving longer afterward. Because these patients often live far from the
      transplant center, their local primary care physicians may be called on to
      evaluate problems as they arise, although all significant issues should be
      handled in conjunction with the transplant team. This paper reviews the primary
      care physician's role in the pretransplantation evaluation, and in coordination
      of long-term care, as well as illustrative cases.

PMID- 9637959
TI  - Managing solitary pulmonary nodules.
AB  - A solitary pulmonary nodule (SPN) on a chest radiograph represents a major
      diagnostic dilemma. The goals of management are to resect malignant tumors
      without delay and to avoid unnecessary thoracotomy if the nodule is benign. But
      because of the difficulty distinguishing benign from malignant nodules, even with
      advances in imaging techniques, these goals cannot be met in all cases.

PMID- 9637960
TI  - A 61-year-old woman with edema, shortness of breath, and pleuritic chest pain.

PMID- 9637961
TI  - Some perspective on Viagramania.

PMID- 9637962
TI  - The promises and risks of inpatient specialization.

PMID- 9637963
TI  - Devolution of power: an interim report card.
AB  - During the mid-1990s liberals hoped that states would enact health insurance
      expansions, while conservatives looked to the states to contain costs. This essay
      considers whether states are meeting these great expectations. I review state
      performance in four policy priorities: encouraging Medicaid clients to enroll in
      managed care; expanding insurance coverage for children; making insurance more
      available and more affordable for the small-business community; and containing
      long-term care costs. The review suggests that states cannot accomplish these
      tasks without federal help. Congress seems to be getting the message and has
      enacted its own child health and insurance reform legislation. This trend is
      overdue and welcome.

PMID- 9637964
TI  - Assessing the new federalism: an introduction.

PMID- 9637965
TI  - A different kind of 'new federalism'? The Health Insurance Portability and
      Accountability Act of 1996.
AB  - The Health Insurance Portability and Accountability Act (HIPAA) of 1996 has been
      praised and criticized for asserting federal authority to regulate health
      insurance. We review the history of federalism and insurance regulation and find
      that HIPAA is less of a departure from traditional federal authority than it is
      an application of existing tools to meet evolving health policy goals. This
      interpretation could clarify future health policy debates about appropriate
      federal and state responsibilities. We also report on the insurance environments
      and the HIPAA implementation choices of thirteen states. We conclude with
      criteria for judging the success of HIPAA and the evolving federal/state
      partnership in health insurance regulation.

PMID- 9637966
TI  - Medicaid managed care in thirteen states.
AB  - This study examines the recent expansion of Medicaid managed care from the
      perspective of the thirteen states in the Urban Institute's Assessing the New
      Federalism project. States are moving to managed care for Medicaid both to
      improve beneficiaries' access and to control the growth in program costs.
      However, we find that despite dramatic growth in enrollment during this decade,
      few states are enrolling the elderly or the disabled--the most expensive Medicaid
      beneficiaries. We also conclude that cost-savings objectives are often at odds
      with goals of contracting with mainstream plans and protecting safety-net
      providers.

PMID- 9637967
TI  - Transformations in public health systems.
AB  - Public health systems are undergoing major changes. Historically, population
      oriented services framed the responsibilities of the public health system. Yet
      over time, clinical services, particularly maternal and child health care, became
      an important component. More recently, many public health agencies have begun to
      refocus on traditional services, largely in response to Medicaid managed care and
      an associated decline in clients. This paper examines such transformations in
      thirteen states.

PMID- 9637968
TI  - State policy on long-term care for the elderly.
AB  - In the thirteen Assessing the New Federalism states, strategies to control the
      rate of increase in long-term care spending are extremely varied, especially in
      comparison with acute care's single-minded focus on managed care. States use
      three broad strategies: offsetting state spending with increased private and
      federal contributions, making the delivery system more efficient, and using
      traditional cost-control mechanisms, including controlling the nursing home bed
      supply and cutting Medicaid reimbursement rates.

PMID- 9637969
TI  - Publicly subsidized health insurance: a typology of state approaches.
AB  - Using information from case studies, published documents, and the Current
      Population Survey, this paper describes and classifies state approaches to
      providing health insurance to low-income populations (as of 1997). It examines
      the link between the scope of state efforts and uninsurance rates for low-income
      populations. Findings indicate that the breadth of state policies contributes to
      differences in insurance coverage for low-income persons across states.

PMID- 9637970
TI  - Changing state and federal payment policies for Medicaid disproportionate-share
      hospitals.
AB  - The Medicaid disproportionate-share hospital (DSH) program has been the subject
      of considerable policy debate throughout the 1990s, prompting Congress to revise
      the program three times since 1991. Using Medicaid administrative data and
      information obtained from twelve state case studies, we examined how the study
      states dealt with the federal reforms. We found a variety of state responses,
      ranging from not spending their full DSH allotments to seeking new, "DSH-like"
      federal money to help support safety-net providers.

PMID- 9637971
TI  - Welfare and immigration reforms: unintended side effects for Medicaid.
AB  - Welfare reform and changes in immigrants' eligibility may lead to significant
      reductions in Medicaid caseloads, even though many states are expanding Medicaid
      eligibility rules to accommodate changes under the new welfare programs. In 1996,
      for the first time in almost a decade, Medicaid participation of adults and
      children fell about 2 percent, and further reductions seem likely in 1997. The
      gradual restrictions on new immigrants also will affect future caseloads.
      Although new initiatives such as the State Children's Health Insurance Program
      (CHIP) should expand health coverage for children, the welfare reform and
      immigration changes will disproportionately lead to loss of insurance among
      adults.

PMID- 9637972
TI  - A broader vision for managed care, Part 1: Measuring the benefit to communities.
AB  - For the past quarter-century managed care plans have been judged almost
      exclusively in terms of their influence on the health and health care of
      individual enrollees. However, policymakers are now paying attention to the ways
      in which health care organizations affect the broader well-being of their
      communities. These forms of "community benefit" emerged originally from legal
      criteria for tax exemption but are increasingly applied to all health care
      organizations, whatever their form of ownership. In this paper we identify
      different paradigms for defining community benefit and trace the factors that
      have encouraged or discouraged their application to health care. We suggest
      several strategies encouraging managed care plans to broaden their goals to
      include community benefit.

PMID- 9637973
TI  - Access to care: how much difference does Medicaid make?
AB  - Using the 1994 Robert Wood Johnson Foundation National Access to Care Survey, we
      examine the likelihood of having a usual source of care, inability to obtain
      needed care, and number of physician visits for persons with private insurance,
      Medicaid coverage, and no insurance. Inability to obtain services is surprisingly
      consistent: For each service, Medicaid enrollees were about half as likely as
      uninsured persons and about twice as likely as privately insured persons were to
      report difficulty. For other access measures, access for those on Medicaid more
      closely resembles that of the privately insured than that of the uninsured.

PMID- 9637974
TI  - Balanced federalism and health system reform.

PMID- 9637975
TI  - Medicaid's problem children: eligible but not enrolled.

PMID- 9637976
TI  - Mental health insurance in the 1990s: are employers offering less to more?

PMID- 9637977
TI  - Consolidation of the inpatient medical rehabilitation industry.

PMID- 9637978
TI  - Managed competition in practice: 'value purchasing' by fourteen employers.
AB  - Many large U.S. companies have transformed their procurement of health benefits
      in the 1990s by combining the principles of managed competition with other
      business tactics to create a business-savvy hybrid of the private sector's own
      design, often referred to as "value purchasing." Until recently, few policymakers
      or health care observers believed that large firms would be a force in health
      system reform. Yet to implement value purchasing, the large companies in this
      study created new organizational forms, provided employees with financial
      incentives to select low-cost health plans, and used business tactics such as
      competitive bidding to negotiate more favorable rates and to improve quality
      among health plans. The financial results were impressive for the companies
      studied. In addition, the companies' demands on the health care delivery system
      are multiplying as the interface between business firms and health care
      organizations changes. These demands will only increase as the practices we found
      become more widespread.

PMID- 9637979
TI  - Independent practice association physician groups in California.
AB  - We surveyed independent practice association (IPA) physician groups in California
      about their approaches to staffing, physician payment, and governance. Most IPAs
      desired more primary care physicians but not more specialists. Capitation was the
      major mode of remuneration for primary care physicians in 77 percent of IPAs, and
      for specialists in 30 percent of IPAs. Most IPAs also used financial incentives
      related to use of referral or ancillary services. Boards of directors were
      dominated by physicians, but governance tended to be centralized rather than
      highly democratic. We found that IPAs mirror many of the broader trends in
      physician staffing and physician payment that exist in managed care
      organizations.

PMID- 9637980
TI  - Managed care and low-income populations: recent state experiences.
AB  - This DataWatch examines the relationship between managed care enrollment and
      access to care for low-income adults with Medicaid and compares their experience
      with that of low-income, privately insured managed care enrollees. Medicaid
      managed care enrollees are more likely than low-income, privately insured managed
      care enrollees to be poorer, have health problems, and experience access
      problems. Compared with low-income populations in fee-for-service care, managed
      care enrollees, whether in Medicaid or privately insured, are not appreciably
      different in having a usual source of care, having a regular provider, or
      emergency room use but report more problems in obtaining care and are more likely
      to be dissatisfied with their health plans.

PMID- 9637981
TI  - Creating partnerships with clinic associations to preserve the safety net.

PMID- 9637982
TI  - How will states implement children's health insurance programs?

PMID- 9637983
TI  - Dealing with Dolly: inside the National Bioethics Advisory Commission.

PMID- 9637984
TI  - Health care and consumers: some amplification.

PMID- 9637985
TI  - Can physicians manage physicians?

PMID- 9637986
TI  - Medicare reform.

PMID- 9637988
TI  - Emergency departments are not the problem.

PMID- 9637987
TI  - Health insurance for low-income adults: the issue of Hispanics.

PMID- 9637989
TI  - The 'shoe-box effect'.

PMID- 9637990
TI  - Doctors as decisionmakers.

PMID- 9637991
TI  - Research needs for rural and environmental health in central Europe.

PMID- 9637992
TI  - Occupational health in Germany and other countries of the European Union.
AB  - Occupational medicine is affected to a much greater extent by national legal and
      social conditions than by clinical issues. The different preconditions specific
      to each country serve to restrict the scientific dialogue on issues of
      occupational medicine. Therefore, in this paper are described the organisation
      and the under- and postgraduate education of occupational medicine in Germany and
      other European countries (Austria, Belgium, Denmark, Italy, United Kingdom). In
      summary one can state that in many member states of the EU there is a lack of
      undergraduate training in occupational medicine for students and there are
      distinct systems for the postgraduate training and assessment of occupational
      physicians. The practice of occupational medicine in the EU countries probably
      has many similarities. The responsibilities of occupational physicians are rather
      comparable, though in some countries the approaches of occupational medical
      prevention and the interest in evaluating the structure, process and outcome of
      many of the activities of occupational medicine seem to recede something into the
      background.

PMID- 9637993
TI  - Separate and combined effects of the outdoor and indoor air quality on chronic
      respiratory symptoms adjusted for allergy among preadolescent children.
AB  - The purpose of the study was (a) to assess whether the respiratory effects of
      outdoor air pollutants may be replicated after correcting for indoor air quality
      (environmental tobacco smoke, home heating and damp or mold houses), (b) to
      evaluate whether the extent of the allergic status of children modifies the
      respiratory health due to air pollution, and (c) to determine whether the higher
      prevalence of respiratory symptoms in more polluted areas of the city may be
      explained by excess in allergy. The survey targeted 1,129 school children, nine
      years of age, attending schools in Cracow, located in the areas with different
      levels of the outdoor air pollution. Based on the measurements obtained from the
      air pollution monitoring stations and the information provided by parents on the
      sources of local emission of air pollutants, four categories of air pollution
      areas have been defined. Chronic phlegm as a single symptom was unrelated to
      allergy but associated with the outdoor air pollution score. The prevalence odds
      ratio (OR) for this symptom between the contrasting areas of outdoor air
      pollution, i.e. very high pollution versus very low, was 5.85 (95% CI: 1.05
      32.6). Except for chronic phlegm, the outdoor air pollution score was associated
      only with hay fever when adjusted for indoor characteristics and allergy. After
      adjustment for air pollution and allergy, the presence of molds or dampness in
      the house was significantly related to hay fever (OR = 2.1, 95% CI: 1.5-3.0),
      wheezing (OR = 1.6, 95% CI: 1.1-2.5), and difficulty in breathing (OR = 2.0, 95%
      CI: 1.2-3.3). In terms of attributable fraction (AF(pop)), the effect of outdoor
      air pollution on the occurrence of allergy in children was significant (AF(pop) =
      22.3%). The impact of allergy on the occurrence of respiratory symptoms (two or
      more respiratory symptoms) was stronger (AF(pop) = 52.1%) than that of the
      outdoor air pollution level (AF(pop) = 21.6%) or that of molds/dampness at home
      (AF(pop) = 14.1%).

PMID- 9637994
TI  - Occupational profile and cardiac risk: possible mechanisms and implications for
      professional drivers.
AB  - There has been at least forty empirical investigations concerning cardiovascular
      disease (CVD) among professional drivers (PDs). Standard cardiac risk factor
      status does not consistently distinguish PDs from other lower risk groups. PDs
      showed more than twice the overall exposure to stressful work factors compared to
      referents. They also showed lower maximum bicycle exercise level with a higher
      double product and higher diastolic blood pressure at the end of exercise
      compared to controls. Catecholamine excretion has been reported to be elevated
      during driving. Ambulatory measurements showed higher systolic and diastolic
      blood pressure in drivers before, during and after driving shifts. Using spectral
      analysis, the low to high frequency ratio was more than doubled towards the end
      of a 4-hour drive compared to the early one and a linear increase in 0.1 heart
      rate variability as a function of distance driven. Reactivity to headlight glare
      has been shown to roughly parallel the degree of CVD severity in PDs with IHD,
      essential and borderline hypertension. It was postulated that PDs with IHD form a
      powerful association between the exposure to glare and the stressfulness of
      driving and this association was resistant to extinction. The occupational
      medicine specialist "should have the authority to check the patient regularly in
      the workplace itself (to ascertain whether or not) the decision to return to work
      is still valid". An integrated diagnostic approach for PDs might entail using
      exercise stress testing, with evaluation of silent myocardial ischaemia and heart
      rate variability during work as well as laboratory tests which simulate aspects
      of their work environment, with catecholamines measured in relation to these
      procedures. Assessment of left ventricular mass and further evaluation of
      atherogenic biochemical abnormalities would be of value for further untangling
      the mechanisms of cardiac risk among PDs.

PMID- 9637995
TI  - Blood lead levels in industrial workers in Poland.
AB  - Occupational exposure to lead occurs in about 1,300 enterprises in Poland.
      According to the 1994 data, based on the reports of the State Sanitary
      Inspectorate, 1,970 persons were employed at that time under conditions of
      exposure exceeding the Polish MAC level of 0.050 mg/m3. The measurements of
      workers' blood lead concentrations (Pb-B) were carried out only in 90 factories.
      In 1996, the Minister of Health and Social Welfare issued a directive stating
      that the Pb-B determinations in employees occupationally exposed to lead are
      compulsory. The aim of the present study was to assess lead exposure of workers
      employed in different branches of the Polish economy, based on Pb-B
      determinations. The measurements were performed on 2,324 male and 165 female
      workers of 13 different types of industry, including manufacture of crystal
      glass, battery industry, copper and zinc smelters, welding in a repair shipyard
      and some other workposts under conditions of lead exposure. The results of the
      determinations indicate that exposure to lead continues to be a serious problem
      in Polish industry. Pb-B concentrations exceeded the newly introduced Polish
      biological exposure index (BEI) value of 500 micrograms/l for men workers in
      about 30% of workers examined in 1996. In about 65% of females under 45 years of
      age the Pb-B concentrations were higher than 300 micrograms/l recommended as BEI
      for this age group. Considering the WHO-recommended health-based maximum
      individual biological action level of 400 micrograms/l, the percentage of the
      employees for whom higher values were found amounted to about 45% for men
      workers. The results point to the necessity of enforcing the implementation of Pb
      B determinations according to the ministerial ordinance as well as of removing
      from exposure the workers with Pb-B levels exceeding the present BEI values. The
      improvement of working conditions and the implementation of health education for
      workers are also the actions to be promptly undertaken. In order to achieve these
      goals a close cooperation is required between the State Sanitary Inspectorate,
      the institutes of occupational health as well as the employers and trade unions.

PMID- 9637996
TI  - Occupational hearing loss among selected farm tractor operators employed on large
      multiproduction farms in Poland.
AB  - A specially selected group of 45 farm tractor drivers were examined in order to
      estimate the degree of occupational hearing loss. The drivers, aged 21-50 years,
      were employed on multiproduction farms. The study showed that the operators under
      study had statistically worse hearing within the range of high frequencies (3-6
      kHz), especially those aged over 30 years, compared to the control group of the
      same age. An intolerable hearing loss (over 20 dB) was noted among 56% of
      operators within the highest frequency range (3, 4 and 6 kHz), and among 22% of
      operators in the range of medium frequencies (0.5, 1, 2 and 3 kHz), with no
      hearing loss observed in the control group. Based on analysis of data concerning
      all operators it was noted that age and the period of employment in agriculture
      were highly correlated with hearing loss (r = 0.45-0.57). A series of
      correlations and linear regression analyses, conducted in two age intervals,
      showed that in the group of young operators (under 35 years) a statistically
      significant, strong correlation was observed between hearing loss and the period
      of employment (right ear: r = 0.60-0.65), whereas in the older age group (over 35
      years) hearing loss was more strongly correlated with age than with the period of
      employment, although this correlation was not statistically significant. The
      results obtained confirmed that the detected hearing loss among operators of farm
      tractors was caused by exposure to occupational noise present on farms.

PMID- 9637997
TI  - Development of occupational exposure limits in Japan.
AB  - The development of occupational exposure limits (OELs) in Japan is discussed by
      describing the OELs of two chemical compounds, benzene and trichloroethylene, as
      typical examples. As for benzene, sufficient epidemiological evidence has
      accumulated indicating that benzene is a human carcinogen. To establish the OEL
      for benzene, the OEL committee of the Japan Society for Occupational Health
      (JSOH) selected 9 cases of acute myeloic or monocytic leukemia out of the 14
      cases of leukemia in the Pliofilm cohort, adopted the exposure estimate of
      Paustenbach et al. (52), and calculated the risk of benzene-induced leukemia by
      means of an average relative risk model. The lifetime risk of leukemia by
      exposure to benzene at 1 ppm for 40 years was calculated as 0.762 x 10(-3) with a
      95% confidence interval between 0.621 x 10(-3) and 0.98.10(-3). The benzene level
      that causes one lifetime excess death from leukemia among 1,000 workers exposed
      to benzene for 40 years was 1.31 ppm, with a 95% confidence interval between 1.01
      and 1.61 ppm. The OEL committee decided that benzene exposure should be
      controlled by a reference value corresponding to a lifetime risk (10(-3) or 10(
      4)) of leukemia rather than by a time-weighted average (TWA) concentration. The
      committee has proposed that the benzene exposure level corresponding to the
      lifetime risk of 10(-3) is 1 ppm and that corresponding to the risk of 10(-4) is
      0.1 ppm. In 1995, the International Agency for Research on Cancer (IARC) changed
      the carcinogenicity classification of trichloroethylene from Group 3 (not
      classifiable as to carcinogenicity to humans) to Group 2A (probably carcinogenic
      to humans). The OEL committee of the JSOH, however, reached the conclusion that
      since it has not been confirmed that trichloroethylene is a human carcinogen, and
      since carcinogenicity, if any, may be based on an epigenetic rather than
      genotoxic mechanism, it is not appropriate to establish the OEL of
      trichloroethylene presupposing that trichloroethylene is a carcinogen. The
      judgment of the OEL committee is that the OEL for trichloroethylene should be
      established on other than carcinogenicity findings, particularly on the basis of
      its neurological effects. In the light of accumulated evidence that a long-term
      exposure to trichloroethylene at 50 ppm will cause neurotoxic effects to
      industrial workers, the OEL committee has proposed 25 ppm (135 mg/m3) as a
      reference value for work environments. Finally, we propose that the general
      environmental air standards of benzene and trichloroethylene should be about
      1/1,000 of the respective reference values for work environment.

PMID- 9637998
TI  - Excess mortality in working age males in Poland: general patterns.
AB  - Since the second World War, excess mortality of males has been steadily growing
      in Poland. The aim of this paper was to analyze the basic relationships between
      excess male mortality and some social and economic factors, with special
      reference to both age and place of residence. Data published in Demographic
      Yearbooks and included in reports produced by the Government Population Council
      were used in the analysis. The excess male mortality is expressed in terms of
      male/female mortality ratio, and also in terms of the difference between the
      average female and male life expectancy. In the early 1990s the general male
      mortality rate in Poland was by 23% higher than the general female mortality
      rate, whereas in males at younger working age (20-44 years) mortality was three
      times higher, and in the older age (45-64 years) groups 2.7 times higher than the
      female mortality. Compared with the majority of European countries, Poland is
      characterised by high rates of excess male mortality, which points to a
      deteriorated health status of the population. At present, excess mortality of the
      working age males is much higher than in the 1960s and 1970s. Our analysis of the
      1960-1994 trends revealed that the highest excess male mortality occurs in the 20
      24 age group. Although recently a falling trend has been observed in the infant,
      juvenile and post working age groups, a continuous increase is noted in the
      working age population of Poland. Causes of death were also included in our
      analysis. Among circulatory diseases, the highest excess mortality was due to
      acute myocardial infarction (the risk of death from this disease was 8 times
      higher for males than for females). Accidents, injuries and poisoning constitute
      another leading group of causes responsible for excess mortality (6/1 male/female
      death risk ratio). The excess male mortality rates are higher in the rural than
      in the urban areas. The excess male mortality was also reflected in the indices
      of average life expectancy. In 1995, the average life expectancy was 67.6 years
      for males and 76.4 years for females. Thus, in Poland males live 8.6 years
      shorter than females on average. Increased excess mortality among the working age
      males, a considerable difference between male and female average life expectancy,
      disturbed demographic male/female balance, these are at least some of the reasons
      why further in depth studies of excess male mortality in Poland should continue.

PMID- 9637999
TI  - Polish bibliography of occupational medicine, 1996. Part 3.

PMID- 9638000
TI  - Timely learning by consensus.

PMID- 9638001
TI  - A quantitative comparison of machined commercially pure titanium and titanium
      aluminum-vanadium implants in rabbit bone.
AB  - Screw-shaped implants made from rods of commercially pure titanium (grade 1) and
      titanium-aluminum-vanadium (grade 5) were machined, and the implant surface
      structures were numerically described before being placed in rabbit tibiae for
      healing periods of 1 months, 6 months, and 12 months. Quantitative comparisons of
      the removal torque (Ncm) necessary to loosen the implants from the bone bed were
      performed. Short-term (1 month) observations revealed no significant differences
      between the two tested materials. However, after 6 and 12 months, the
      commercially pure titanium implants were significantly more stable in the bone
      bed, as compared to the alloy samples. After 6 months, the commercially pure
      titanium had a mean removal torque of 29 Ncm versus 23 for the alloy (P = .01),
      and after 12 months, the mean removal torque was 38 Ncm for commercially pure
      titanium as compared to 35 Ncm for the alloy (P = .01). Quantifications of the
      bone tissue response to the materials did not show any significant differences;
      however, the commercially pure titanium showed a tendency to have a higher
      percentage of bone in contact with the implant as compared to the alloy screws.
      Bone volumes in the threads were similar. The absence of any quantitative light
      microscopic difference after 1 month following placement may relate to the fact
      that there was a sparse amount of bone, since the tissue was in the
      organization/granulation phase. After 6 and 12 months of follow-up, substantial
      bone formation had occurred, resulting in significantly increased removal torques
      for the commercially pure titanium samples.

PMID- 9638002
TI  - The treatment dilemma of the furcated molar: root resection versus single-tooth
      implant restoration. A literature review.
AB  - Successful treatment of furcated molar teeth presents the periodontist and
      prosthodontist with a challenging dilemma. Accepted treatment modalities include
      chemotherapeutic maintenance, root planning, open flap debridement, modified
      Widman flap, bone grafting with and without guided tissue regeneration, and
      osseous resection with and without root removal. Determining the appropriate
      treatment for an individual patient that is both cost-effective and offers the
      greatest long-term prognosis can be a daunting task. The literature is replete
      with studies of different therapeutic alternatives for furcated molar teeth. A
      relatively new treatment option is complete removal of the tooth combined with
      ultimate placement of an endosseous implant and restoration with a single crown.
      A review of the relevant literature with special emphasis on root resection
      therapy and single molar implant placement is presented. The relative merits of
      each treatment modality and guidelines for their use are discussed.

PMID- 9638003
TI  - Implants placed in immediate extraction sites: a report of histologic and
      histometric analyses of human biopsies.
AB  - Five titanium plasma-sprayed implants were biopsied from a human volunteer 6
      months after placement. Four test implants had been placed in immediate
      extraction sockets, while one implant was placed in a mature site and served as a
      control. The histologic analysis demonstrated that all five implants achieved
      osseointegration as demonstrated by light microscopy, whereas a varying degree of
      bone-implant contact was observed. The non-loaded control implant had the highest
      percentage of bone-implant contact, 72%, followed by the two implants placed in
      the canine sites presenting with a horizontal defect dimension of 1.5 nm or less.
      These implants were placed without a barrier membrane, but in a submerged
      fashion. The histometric analysis showed a mean bone-implant contact of 50% for
      these two implants. The lowest mean bone-implant contact (17%) was observed for
      the two molar implants, which had horizontal defect dimensions of 4 mm; these
      implants were placed in a non-submerged fashion with the implants perforating an
      expanded polytetrafluoroethylene membrane. The authors concluded that
      osseointegration may occur in immediate extraction sites in humans using titanium
      implants with a plasma-sprayed surface. The horizontal component of the peri
      implant defect was apparently the most critical factor relating to the final
      amount of bone-implant contact.

PMID- 9638004
TI  - Bone response to functioning implants in dog mandibular alveolar ridges augmented
      with distraction osteogenesis.
AB  - The specific aim of this study was to determine the response of alveolar bone
      after it was augmented vertically using distraction osteogenesis and subsequently
      loaded with implant restorations. Four dogs each had four implants placed
      horizontally into an edentulous mandibular quadrant and, after integration, a
      distraction osteogenesis device was fabricated in the laboratory. An osteotomy
      was made to allow the crest of the alveolar ridge to be distracted vertically.
      After 10 mm of vertical distraction, the device was stabilized with light cured
      resin. Following bone fill confirmation of the distraction gap at 10 weeks, two
      implants were placed into the ridges, one in distracted bone and one in
      nondistracted bone. After 4 months for implant integration, freestanding
      prostheses were fabricated. Crestal bone levels were evaluated throughout the
      period of function. Animals were sacrificed after 1 year of loading, for
      histologic evaluation of the bone. The vertical ridge augmentation averaged 8.85
      +/- 1.05 mm after 10 weeks of healing following distraction, without change over
      1 year of implant loading. Histologic examination showed that bone had formed
      between the distracted segments, creating an augmented ridge. The average
      thickness of the labial cortex in the distraction gap was significantly thinner
      than the lingual cortex in distracted bone and the lingual and labial
      nondistracted cortical bone. The presence of the dental implant did not
      significantly affect cortical bone thickness. Serial sections showed that
      implants remained integrated and functional without soft tissue inflammation.
      Dental implants placed into alveolar ridges augmented with the technique of
      distraction osteogenesis maintained bone and were functional for the length of
      this study.

PMID- 9638005
TI  - Telescopic prostheses for implants.
AB  - This retrospective study investigated the outcome of 73 telescopic implant
      supported fixed prostheses. Fifty-four prostheses were entirely cement-retained,
      and 19 incorporated a screw-clamping unit. The rate of complications was low and
      in most cases minor in nature. Cement-retained prostheses involving a distal
      cantilevered extension required the greatest postoperative maintenance. Despite
      the small number of combined screw- and cement-retained prostheses, the lack of
      complications and ease of retrievability make this approach worthy of further
      study.

PMID- 9638006
TI  - Report of 302 consecutive ridge augmentation procedures: technical considerations
      and clinical results.
AB  - Three hundred two consecutive ridge augmentation procedures (289 in a
      buccolingual and 13 in an apico-occlusal direction) were performed in 284
      patients. Gore-Tex membranes of various configurations were used in conjunction
      with various nonautogenous particulate materials. Two hundred ninety-one of the
      augmented ridges (279 buccolingual and 12 apico-occlusal augmentations)
      demonstrated sufficient regenerated hard tissues for implant placement in ideal
      prosthetic positions. This represents an overall "success" rate of 96%, 97% for
      horizontally augmented ridges and 92% for vertically augmented ridges. A total of
      574 implants were placed in the augmented ridges; 346 of these implants have
      subsequently been uncovered and restored. Seven implants failed to achieve
      osseointegration, and three implants (in one patient) were lost in function, for
      an overall survival rate of 97% for the uncovered implants.

PMID- 9638007
TI  - Mandibular implant-retained overdenture: finite element analysis of two anchorage
      systems.
AB  - Transmission of masticatory load in mandibular implant-retained overdentures was
      evaluated using a three-dimensional finite element model. The reaction forces on
      the distal edentulous mucosa and the stress on the perimplant bone were compared
      in overdentures retained either by two ball attachments or by two clips on a bar
      connecting two implants. In the finite element model, a 35 N load on the first
      mandibular molar induced a greater reaction force on the distal edentulous ridge
      mucosa of the nonworking side when the overdenture was anchored by ball
      attachments than with the clips/bar attachment. Stress on peri-implant bone was
      greater with the clips/bar attachment than with the ball attachment.

PMID- 9638008
TI  - Mobility assessment with the Periotest system in relation to histologic findings
      of oral implants.
AB  - The relationship between mobility assessment with the Periotest system and
      histologic findings was evaluated for oral implants. Five screw-type implants of
      pure titanium were placed in the mandibles of four monkeys. Two implants in each
      monkey were occlusally overloaded. These implants were brushed once a week.
      Plaque was allowed to accumulate around unloaded implants with abutments in the
      same monkeys. During the experiment, six of eight implants with occlusal overload
      showed increased manually detectable mobility. Two of these were lost. After 18
      months of experimentation, the mobility was assessed using the Periotest system.
      Sections of the implants and surrounding tissue were cut. For the excessive
      occlusally loaded implants with manually detectable mobility, positive Periotest
      values were recorded, and for all other implants the values were negative (range
      = -7 to -2). All implants with plaque accumulation were histologically
      osseointegrated but showed marginal bone loss. Two of the implants with occlusal
      overload had lost osseointegration completely, and two other implants were
      osseointegrated in the apical part only. A statistically significant association
      between the Periotest values and the histologic bone level or the proportion of
      bone-implant contact was observed. If only clinically stable implants (i.e.,
      without manually detectable mobility or with a negative Periotest value) were
      included in the analysis, no significant correlation was found. The Periotest
      values revealed only slightly more information concerning the osseointegration of
      implants than manual mobility assessments.

PMID- 9638009
TI  - Mandibular onlay grafting using prefabricated bone grafts with primary implant
      placement: an experimental study in minipigs.
AB  - The aim of this experimental study was to evaluate the use of prefabricated
      autogenous bone grafts as onlay grafts to the mandible. Excess bone of 10 x 12 x
      40 mm was produced inside blocks of pyrolyzed bovine bone under a polylactic
      membrane coverage on the outside of the mandible in 15 adult Gottingen minipigs.
      After 5 months, this bone was harvested and transferred to the premolar region of
      the mandibular body in 10 animals. Onlay grafts of mandibular bone were used as
      controls for the transplanted prefabricated grafts. All grafts were fixed by
      primary placement of one titanium implant each. Five animals served as ungrafted
      controls. Evaluation was performed after 3 months and 5 months, respectively. Two
      animals were lost to evaluation, and one scaffold became infected. Eleven of the
      remaining 12 scaffolds showed sufficient bone ingrowth for grafting. Three months
      after transplantation, bone volume of the prefabricated grafts was almost
      completely preserved, with only minimal resorption in the superficial pores of
      the scaffolds, while the control grafts exhibited partial resorption. The
      titanium implants, which had been placed at the time of only grafting, exhibited
      direct bone-implant contact. Five months after grafting, all titanium implants
      showed complete osseointegration, with direct bone-implant contact. The grafted
      bone exhibited a significant increase in bone density by appositional bone
      formation. The control grafts were nearly completely resorbed at that time.

PMID- 9638010
TI  - Tridimensional reconstruction of knife-edge edentulous maxillae by sinus
      elevation, onlay grafts, and sagittal osteotomy of the anterior maxilla:
      preliminary surgical and prosthetic results.
AB  - The possibility of placing endosseous implants in the edentulous maxilla is
      frequently reduced by inadequate bone volume of the residual ridge. In totally
      edentulous maxillae with knife-edge conformation, insufficient thickness is
      frequently associated with insufficient height of the residual ridge in the
      posterior maxilla because of pneumatization of the maxillary sinuses. This
      surgical method combines grafting of the maxillary sinuses, onlay grafts on the
      buccal side of maxillary posterior segments, and sagittal osteotomy of the
      anterior maxilla with interpositional bone grafts. Five to six months after
      maxillary reconstruction, Branemark implants were placed and, after
      osseointegration occurred, implant-supported dental prostheses were fabricated.
      Three patients have been treated with this method and 22 implants have been
      placed. The mean follow-up after final prosthetic rehabilitation has been 16
      months; survival rate has been 100%. Despite the small number of patients and the
      short follow-up, preliminary results have shown very promising results.

PMID- 9638011
TI  - Prognostic variables associated with implant failure: a retrospective
      effectiveness study.
AB  - The purpose of this study was to determine implant survival rates by means of
      life table analyses for a cohort of patients not part of a prospective efficacy
      trial and treated by practitioners at varying experience levels. Prognostic
      variables associated with implant failure were identified by means of
      proportional hazards models and advanced statistical methods that account for
      patient effects. Ninety-nine consecutive patients treated from 1987 to 1991 with
      follow-up to 1994 were included in this retrospective study. A total of 384
      dental implants (79.7% Branemark, 19.3% IMZ plasma-sprayed, 1% IMZ hydroxyapatite
      coated) were placed and subsequently supported 108 prostheses. Survival and
      proportional hazards modeling were used to generate Kaplan-Meier survival curves
      and to identify variables associated with implant failure. Survey data analysis
      was used to adjust for any patient effects for variables identified as
      significant through the proportional hazards models. Thirty-four implants failed
      over the follow-up period (median follow-up time 3.6 years), resulting in an
      overall failure rate of 8.9%. Seventeen of 99 patients experienced an implant
      failure. When prosthesis type was excluded from the modeling process, survey data
      analysis identified posterior location and an implant width of less than 4.0 mm
      as being associated with implant failure (all P < .05).

PMID- 9638012
TI  - Experience with osseointegrated implants placed in irradiated tissues in Japan
      and the United States.
AB  - A survey was undertaken to analyze osseointegrated implants placed in irradiated
      maxillae and mandibles. It was found that nine centers in Japan and two centers
      in the United States had placed 228 implants in 44 patients. Of 228 implants, 59
      were placed in the maxilla, 169 in the mandible. Three of 169 implants placed in
      irradiated mandibles were removed; 17 of 59 were removed from maxillae. One
      hundred nineteen implants were placed in the mandible without adjunctive
      hyperbaric oxygen treatment, of which only 2 were removed. From these results, it
      is suggested that osseointegrated implants can be placed in the irradiated
      mandibles of selected patients without hyperbaric oxygen treatment.

PMID- 9638013
TI  - Prosthetic treatment using an osseointegrated implant after secondary bone
      grafting of a residual alveolar cleft: a case report.
AB  - Conventionally, for dental reconstruction after bone grafting of the congenital
      residual alveolar cleft, a fixed prosthesis or removable partial denture is used.
      In this paper, residual alveolar cleft reconstruction with an osseointegrated
      implant following secondary bone grafting is described. The patient underwent
      secondary bone grafting of the residual alveolar cleft at the age of 18 years.
      One osseointegrated implant was placed in the bone bridge 8 months after bone
      grafting. No problems up to 1 year after the fabrication and placement of the
      fixed prosthesis have been observed.

PMID- 9638014
TI  - Comparative study of guided bone regeneration using absorbable and permanent
      barrier membranes: a histologic report.
AB  - In an experimental study using the Gottingen minipig, Gore-Tex, Gore Resolut, and
      Vicryl barrier membranes were tested for their efficacy in guided bone
      regeneration. The results were compared to those of autologous periosteum. The
      strongest reossification was seen in the bone defects covered with Gore-Tex;
      however, time-dependent disintegration phenomena, which had already been observed
      in preliminary examinations, were clearly established. After investigations of
      cell cultures to which human macrophages were added, the latter findings can be
      interpreted as the result of a physicochemical process, since a direct attack by
      the macrophages was not seen in vitro. Of the membranes used, the absorbable ones
      tended to collapse, depending on the size of the defect that was used, and they
      did not enhance reossification as much as did the permanent membranes. The
      periosteum-covered defects showed a satisfactory degree of regeneration, and no
      differences were observed between freely transplanted and pedunculate periosteum.

PMID- 9638015
TI  - Immediate implants placed into infected sites: a histomorphometric study in dogs.
AB  - The study the effect of chronically infected sites on the immediate placement of
      implants, periapical lesions were induced in the third and fourth premolars of
      four dogs and the contralateral teeth were used as controls. Nine months after
      the induction of periapical lesions, experimental and control teeth were
      extracted, and 28 IMZ implants were immediately placed. After a healing period of
      12 weeks, the animals were sacrificed, the hemimandibles were removed, and
      specimens were prepared to be hard-sectioned and stained with toluidine blue. All
      areas healed without inflammation or exudation and all implants were clinically
      immobile and were radiographically determined to be surrounded by normal
      appearing bone. Histologically, there were no signs of infection, and the
      histomorphometric analyses revealed that 28.6% and 38.7% had osseointegrated for
      the experimental and control implants, respectively. The difference was not
      statistically significant. It was concluded that chronically infected sites, such
      as those showing signs of periapical pathosis, may not be a contraindication for
      immediate implants, if certain clinical measures and preoperative and
      postoperative care are taken.

PMID- 9638016
TI  - Minimally invasive diagnosis and surgery in breast screening.

PMID- 9638017
TI  - Feasibility of population based screening in Ireland.
AB  - Population registers have formed the basis for computerised call/recall registers
      for screening programmes in many countries and have been important in achieving
      high uptakes in targeted populations. The absence of a population register for
      the ECCLES (European Campaign against Cancer, Localisation, Evaluation &
      Screening) Breast Screening Project necessitated the development of a special
      register of women in the target age group. The data sources used to build the
      project register were the Eastern Health Board and North Eastern Health Board
      General Medical Services database, Voluntary Health Insurance data and self
      registration with the project. The register captured 86.3 per cent of the target
      population. A debate on the merits and difficulties associated with the setting
      up of a population register in Ireland is now timely.

PMID- 9638018
TI  - Post herpetic neuralgia: a review.

PMID- 9638019
TI  - Transport of digested decontaminated sputum specimens to a central laboratory for
      testing for M. tuberculosis by Amplicor MTB test.
AB  - Rapid diagnosis of tuberculosis may improve management of infected patients and
      facilitate infection control procedures. The relatively slow growth rate of M.
      tuberculosis and the limited sensitivity and specificity of microscopy make rapid
      diagnosis difficult. Nucleic acid amplification techniques have been extensively
      studied for the detection of M. tuberculosis DNA and a number of commercial
      products for detection of M. tuberculosis nucleic acid in clinical specimens are
      now available. As performance of diagnostic PCR at central reference laboratories
      may be desirable, the impact of specimen transport on the performance of the
      Amplicor MTB PCR assay is of practical importance. We have assessed the
      performance of the Amplicor MTB PCR on specimens submitted and initially
      processed in laboratories in 3 cities and then transported to a single laboratory
      for PCR assay. The overall sensitivity of the PCR test was 97 per cent and the
      corrected specificity was 100 per cent. All of 23 culture positive specimens
      collected locally were PCR positive compared with 10 of 11 culture positive
      specimens transported from elsewhere. In this study transportation of digested
      decontaminated specimens to a central laboratory either frozen at -20 degrees, or
      overnight at room temperature had no apparent effect on the performance
      characteristic of the Amplicor MTB PCR assay.

PMID- 9638020
TI  - Acquired von Willebrand's disease.
AB  - von Willebrand's disease (vWD) is the commonest inherited bleeding disorder in
      man with an estimated incidence of 1 per thousand of the population. Acquired von
      Willebrand's disease (AvWD) is rare with less than 70 cases reported. AvWD is
      usually associated with autoimmune or clonal proliferation disorders and whilst
      the precise mechanism of acquired deficiency of von Willebrand factor (vWF) is
      poorly understood, the most likely candidate mechanism(s) are; antibodies
      inactivate or form a complex with immunologic or functional sites on vWF, or vWF
      multimers are selectively absorbed by malignant cells. Unlike hereditary vWD, the
      acquired form of the disease can be exceedingly difficult to manage. We report 4
      cases of AvWD diagnosed at our centre over the past 3 yr. There was no evidence
      of a previous personal or family history of bleeding in any of the patients and
      AvWD was confirmed by laboratory testing. All 4 patients had a recognised primary
      medical condition known to be associated with AvWD (Waldenstrom's
      Macroglobulinaemia in 2 patients, hypothyroidism in 1 patient and monoclonal
      gammopathy of unknown significance (MGUS) in 1 patient). The acquired haemostatic
      defect corrected following treatment of the primary condition in 3 patients with
      the other patient requiring on demand von Willebrand Factor replacement to
      control spontaneous and surgery induced bleeding.

PMID- 9638021
TI  - Role of carbon fibre implants in osteochondral defects of the knee.
AB  - Articular cartilage defects of the knee are a common condition diagnosed at
      arthroscopy. The management of these osteochondral lesions is controversial. We
      present our experience using carbon fibre implants to repair these defects in 18
      patients. Eleven patients (61 per cent) had an osteochondral defect of the medial
      femoral condyle. Two patients had isolated patellar defects. The mean knee
      assessment and functional scores were 75 and 80 respectively using The Knee
      Society Clinical Rating System. Serial post-operative M.R.I. scanning revealed
      that there was no loss of implant position with an extensive local tissue
      response and good joint congruity. Overall, 11 patients (61 per cent) returned to
      their normal sporting activity, while 3 patients (18 per cent) had a poor result.
      One of these underwent a patellectomy. We conclude that carbon fibre implants may
      have a role to play in the management of osteochondral defects of the femoral
      condyles.

PMID- 9638022
TI  - Uncensored open access gastroscopy--limited resources--unlimited demand.
AB  - In the first 3 yr of an uncensored open access gastroscopy service in a County
      Hospital, 891 patients attended for first gastroscopy. The data on these patients
      is presented and compared with a randomly selected group who attended for
      gastroscopy in the yr prior to the establishment of the service having come to
      the normal Consultant clinics. In the open access group the gastroscopy
      examination was normal in 29 per cent (32 per cent comparator group), 31 per cent
      had major abnormalities (33 per cent comparator group) and 40 per cent had minor
      abnormalities (35 per cent comparator group). Delay time from referral to
      endoscopy was 37 days for open access patients (45 days comparator group). Only 6
      per cent of open access patients were brought back to O.P.D. (47 per cent
      comparator group) and 72 per cent of open access patients returned directly to
      their family doctor (28 per cent comparator group). A comparison of the Clonmel
      findings with British centres reporting their results shows a broadly similar
      picture. It is concluded that almost 1,300 unnecessary clinic visits were avoided
      by the provision of the open access service, some reduction in delay time to
      gastroscopy was achieved, the family doctor maintained control of patient
      management in the great majority of patients, the pattern of referral was not
      inappropriate and compared very well with the comparator group. Over the 3 yr
      there was a large increase in the number of gastroscopies performed which caused
      resource difficulties. It is recommended that adequate planning of these
      requirements should be carried out before an open access service is started. At
      least 1 additional dedicated gastroscopy only endoscopy service per week would be
      required.

PMID- 9638023
TI  - The benefit of lowering cholesterol: relative risk can be absolutely misleading!

PMID- 9638024
TI  - Epidemiology of hepatitis E virus in male blood donors in Jeddah, Saudi Arabia.
AB  - To our knowledge, only a few epidemiological reports on the prevalence of
      hepatitis E antibodies in Saudi blood donors have been published. Men of several
      nationalities, donating blood at King Khalid National Guard Hospital (Jeddah,
      Saudi Arabia) were selected (n = 593) for this study examining the seroprevalence
      of hepatitis E virus (HEV) in the local male donor population and testing the
      relationship of the antibody to HEV (anti-HEV) to donor characteristics using
      Odds Ratio (OR) and Chi-square statistic. The prevalence of anti-HEV in the group
      examined was 16.9 per cent (100/593). The seroprevalence for Saudi donors was
      14.8 per cent compared with 33.3 per cent for non-Saudis of Middle Eastern
      origin. Donors who were 40 yr and over had significantly higher seroprevalence
      than those donors who were 30 yr or younger (OR = 2.5, p = 0.006). There was a
      significant association between anti-HEV and anti-HCV with donors who were
      positive to anti-HCV having about 5 times the risk of HEV than those who were
      anti-HCV negative (p = 0.02). These findings demonstrate the high seroprevalence
      rate of anti-HEV among male blood donors in Saudi Arabia.

PMID- 9638025
TI  - Exaggerated blood pressure response to exercise: pathophysiologic mechanisms and
      clinical relevance.
AB  - The assessment of blood pressure during bicycle ergometry or treadmill exercise
      is considered of paramount importance in establishing the eligibility of an
      athlete to enter competitive sports. One of the potential risks related to an
      exaggerated blood pressure response to stress testing is that in the long run
      repetitive blood pressure peaks triggered by physical activity may determine
      chronic target organ damage or favour the occurrence of an acute cardiovascular
      event. Our concern should be addressed particularly to the competitive athlete,
      insofar as training seems to increase the blood pressure reactivity to dynamic
      exercise. However, studies performed in young borderline hypertensive subjects
      have demonstrated that blood pressure level during steady-state long lasting
      exercise can not be predicted by the maximum blood pressure attained during a
      short-lasting incremental effort. Several prospective studies have demonstrated
      that excessive increases in blood pressure during exercise may be a marker of
      future sustained hypertension and of increased risk of cardiovascular mortality.
      The steeper rise in exercise blood pressure in normotensive subjects prone to
      develop hypertension and its complications seems to be due to a failure to reduce
      total peripheral resistance adequately during exercise, as a result of initial
      structural vascular changes which would pre-date the tonic elevation in the blood
      pressure.

PMID- 9638027
TI  - Ultra-triathlon-related blood-chemical and endocrinological responses in nine
      athletes.
AB  - BACKGROUND: Objective of this study was to get more insight in hematology,
      biochemistry, and endocrinology of ultra-endurance exercise, to improve knowledge
      in this field, supplementation, and medical care of affected athletes. METHODS: A
      large body of individual hematological, biochemical, and endocrinological
      parameters was analyzed in the blood taken from ultra-athletes before and after
      completing the 1993 Colmar ultra triathlon covering 7.5 km swimming, 360 km
      cycling, and approximately 85 km running. PARTICIPANTS: Nine experienced ultra
      athletes participated in the study. A follow-up was not possible since the
      athletes left Colmar within 24 hrs after the contest. RESULTS: The athletes
      finished the ultra-contest at rankings 4, 5, 7, 8, 9, 11, 18, 22, 23 in a total
      time between 23:38:53 and 27:54:30 hr:min:sec. Their final body mass (68.6 +/- 1
      kg) was significantly lower than at baseline (71.9 +/- 4.2 kg). Non of the
      athletes made use of medical care. Data after this contest reflect mild
      hyponatremia, intravascular hemolysis, increased triglyceride turnover, acute
      phase reaction, hyperaldosteronemia 2061 +/- 1013 pmol.L-1), hypercortisolemia
      971 +/- 486 nmol.L-1), hyper-growth-hormonemia (median 6.8 ng.ml-1),
      hypoinsulinemia, hypo-free-testosteronemia (42 +/- 17 pmol.L-1), protein
      catabolism, depressed testicular function, oliguria, and muscle cell leakage.
      CONCLUSIONS: In our opinion, data presented do not reflect any acute health risks
      in healthy athletes who are well prepared and carefully supplied during such a
      contest.

PMID- 9638026
TI  - Effects of prolonged strenuous endurance exercise on plasma myosin heavy chain
      fragments and other muscular proteins. Cycling vs running.
AB  - BACKGROUND: This study evaluates creatine kinase, myosin heavy chain, and cardiac
      troponin blood levels following three types of exercise: 1) short-distance uphill
      or downhill running; 2) alpine ultramarathon; and 3) alpine long-distance
      cycling. METHODS:  EXPERIMENTAL DESIGN: Comparative field study; follow-up up to
      10 days. SETTING: Department of Sports Medicine. All biochemical markers were
      analysed at the Department of Medical Chemistry and Biochemistry. PATIENTS OR
      PARTICIPANTS: Subjects included healthy, trained males (N = 53). All subjects
      were nonsmokers and free from medication prior to and during the study. Each
      volunteer was an experienced runner or cyclist, who had at least once
      successfully finished the Swiss Alpine Marathon of Davos or the Otztal
      Radmarathon before. INTERVENTIONS: Running or cycling. MEASURES: Plasma
      concentrations of creatine kinase, myosin heavy chain fragments and cardiac
      troponins were measured to diagnose skeletal and cardiac muscle damage,
      respectively. RESULTS: Skeletal muscle protein release is markedly different
      between uphill and downhill running, with very little evidence for muscle damage
      in the uphill runners. There is considerable muscle protein leakage in the
      ultramarathoners (67 km distance; 30 km downhill running). In contrast, only
      modest amounts of skeletal muscle damage are found after alpine long-distance
      cycling (230 km distance). CONCLUSIONS: This study proves that there is slow
      twitch skeletal muscle fiber damage after prolonged strenuous endurance exercise
      and short-distance downhill running. Exhaustive endurance exercise involving
      downhill running and short-distance downhill running lead to more pronounced
      injury than strenuous endurance exercise involving concentric actions. From our
      results there is no reason for suggesting that prolonged intense exercise may
      induce myocardial injury in symptom-less athletes without cardiac deseases.

PMID- 9638028
TI  - Changes in plasma volume following intense intermittent exercise in neutral and
      hot environmental conditions.
AB  - BACKGROUND: The purpose of the present investigation was to examine the effect of
      supramaximal short duration intermittent exercise in neutral and hot
      environmental conditions on changes in plasma volume. The return of plasma volume
      (PV) to pre-exercise values following different recovery conditions was also
      examined. METHODS: Experimental design. Within subject design in which one way
      analysis of variance was conducted. SETTING: Research, sports science academic
      institute. PARTICIPANTS: Ten trained men, 25.5 +/- 3/1 (yrs), volunteers.
      INTERVENTIONS: Subjects performed six 1-min bouts of exercise at 100% VO2peak on
      a cycle ergometer, with 4-min rest intervals between the bouts. Each subject
      exercised twice in thermoneutral (22 degrees C, 40% RH) and twice in hot (35
      degrees C, 30% RH) conditions. Exercise was followed by either 40 min of passive
      recovery (sitting) or by 20 min active recovery (cycling at 35% VO2peak) and 20
      min passive recovery, named thereafter "active recovery". MEASURES: Hematocrit
      (Hct) and hemoglobin (Hb) were determined upon entry into the climatic chamber
      following 20 min rest in the chamber (pre-exercise), immediately postexercise,
      and 40 min postexercise. From the changes in Hct and Hb, PV changes were
      calculated. RESULTS: There was a significant decrease in PV immediately
      postexercise. However, there was no significant difference between the two types
      of environmental conditions and no difference between the two types of recovery.
      PV increased significantly following recovery and returned to pre-exercise values
      following 40 min of recovery. CONCLUSIONS: Changes in PV caused by maximal short
      duration cycling bouts is not affected by environmental conditions, PV returns to
      its pre-exercise values within 40 min of recovery regardless of the recovery
      mode.

PMID- 9638029
TI  - Comparison of the aerobic contributions to Wingate anaerobic tests performed with
      two different loads.
AB  - BACKGROUND: The purpose of the present study was to compare the aerobic
      contribution of the Wingate anaerobic test by increasing the test load and power
      output. METHODS:  SETTING: The study was performed in the Physiology Department
      of the Faculty of Medicine, Selcuk University. PARTICIPANTS: Thirty sedentary
      male university students volunteered to this study. EXPERIMENTS: The subjects
      performed two Wingate tests against resistance of 75 g.kg-1 and 95 g.kg-1 body
      weight on Monark 818E bicycle ergometer. Breath-by-breath oxygen consumption
      rates were measured using an automated metabolic measurement chart (Sensormedics
      2900). Aerobic contribution was determined by dividing energy equivalence of net
      oxygen consumption to the total work. RESULTS: The mean total work values
      obtained from tests performed at 75 g.kg-1 and 95 g.kg-1 loads were 13.9 +/- 1.5
      kjoules and 14.5 +/- 1.8 kjoules (t = 2.32, p = 0.03). Mean total oxygen
      consumptions were 765 +/- 105 ml and 770 +/- 110 ml, respectively (t = 0.24, p =
      0.81). Assuming 20% mechanical efficiency for both tests, aerobic contributions
      were calculated as 19.5 +/- 3.7% and 18.9 +/- 3.7%, respectively (t = 1.01, p =
      0.30). CONCLUSIONS: Although the power outputs of the two tests were different,
      the difference between aerobic contributions was not statistically significant.
      So, it was failed to say that the increase in the power outputs might be related
      to higher contribution of anaerobic processes. However, if different mechanical
      efficiencies could be used, relationship between aerobic contributions of two
      tests might have been different.

PMID- 9638030
TI  - The use of a fixed value of RPE during a ramp protocol. Comparison with the
      ventilatory threshold.
AB  - BACKGROUND: The purpose of our investigation was to assess the use of a fixed
      value (12-13) of the Rating of Perceived Exertion (RPE) scale (6-20) as a valid
      method for the determination of the workload corresponding to the ventilatory
      threshold (VT) during a ramp protocol on a cycle ergometer. METHODS: Eleven
      trained cyclists (22 +/- 3 years of age; VO2max: 65.2 +/- 12.4 ml.kg-1.min-1)
      were selected as subjects. DESIGN: Each of the subjects performed a ramp protocol
      on a cycle ergometer (starting at 25 W, with increases of 25 W.min-1 until
      exhaustion). Gas exchange data were analysed continually during the test to
      detect the ventilatory threshold (VT) of the subjects. In addition values of RPE
      were obtained from each subject in the last 15 sec of each 2-minute-interval
      during the tests, and immediately after exhaustion. The RPE threshold (RPET) was
      defined as a constant value of 12-13. Mean values of VT and RPET were expressed
      as VO2 (ml.kg-1.min-1), %VO2max, heart rate (bpm) and power output (W), and were
      compared using a paired "t"-test. RESULTS: No significant difference (p < 0.05)
      was found between mean values of VT and RPET, when both parameters where
      expressed either as VO2, %VO2max, heart rate, or power output. CONCLUSIONS: In
      conclusion, a fixed value (12-13) of the RPE scale might be used to detect the
      exercise intensity corresponding to VT. Such parameter may therefore be used for
      exercise prescription in substitution to more sophisticated methodologies.

PMID- 9638031
TI  - Blood lactate concentrations during exercise: effect of sampling site and
      exercise mode.
AB  - BACKGROUND: The purpose of the study was to compare blood lactate concentrations
      determined in blood sampled from three sites (finger capillary, ear-lobe
      capillary, and forearm vein) during exercise on three different ergometers (a
      cycle ergometer, a treadmill and an arm-crank ergometer). METHODS: A total of 312
      well-trained subjects performed either a six-minute steady-state exercise (n =
      219) or an incremental exercise test until exhaustion (n = 93). Blood was sampled
      from two sites after each exercise test and at the end of each stage of the
      incremental protocol, 852 pairs of blood samples were analysed. RESULTS: Results
      showed that, when exercise was performed on a cycle ergometer or a treadmill, no
      significant differences between venous and ear capillary samples were observed
      whereas finger capillary values were higher. On an arm-crank ergometer, venous
      and finger capillary lactate concentrations were usually higher than ear
      capillary values with some discrepancies depending on the times of sampling.
      CONCLUSIONS: We conclude that lactate values may differ depending on the sampling
      site and the type of exercise mode. An ear capillary sample may be preferred
      because it is less affected by lactate release in the arms and easier to obtain.

PMID- 9638032
TI  - Identifying the integrated electromyographic threshold using different muscles
      during incremental cycling exercise.
AB  - BACKGROUND: The purpose of this study was to identify the IEMG threshold in the
      vastus lateralis (VL) and rectus femoris (RF) muscles during progressive,
      incremental exercise and to relate these thresholds to the ventilatory threshold
      (Tvent). METHODS: Ten men (age: 23.40 +/- 3.13 yrs, mass 76.64 +/- 8.13 kg, %
      fat: 8.81 +/- 2.32, VO2peak: 66.37 +/- 10.61 ml.kg.min-1) with cycling experience
      completed a graded exercise test on a cycle ergometer by cycling at 90 rpm using
      45 watt increments at two minute intervals. Oxygen uptake was measured
      continuously and the IEMG activity of the VL and RF was calculated during the
      last 5 s of each minute. The mean for the IEMG of 6 to 7 complete pedal
      revolutions was used as the final value. Tvent was visually identified using the
      VE/VO2 and V-slope methods. The IEMG threshold for VL and RF was visually
      identified at the inflection point where a non-linear increase in IEMG occurred.
      Comparisons between Tvent and IEMG thresholds were made using dependent means "t"
      tests. RESULTS: Results showed that an IEMG threshold was identified in all 10
      subjects for the RF, but in only 5 of 10 subjects for the VL. However, when
      identified, the IEMG threshold for VL was similar to RF.VO2 at IEMG threshold for
      RF (3.53 +/- 0.36 L.min-1) was not significantly different from Tvent (3.36 +/-
      0.42 L.min-1). CONCLUSIONS: These results show that the IEMG threshold is more
      consistently detected in the RF compared to VL during incremental cycling
      exercise. In addition, the IEMG threshold for RF was closely related to Tvent and
      provides an alternative means to assess the ventilatory threshold.

PMID- 9638033
TI  - Caffeine consumption habits do not influence the exercise blood pressure response
      following caffeine ingestion.
AB  - BACKGROUND: The purpose of this study was to determine if the BP response during
      walking following caffeine ingestion differed between those who regularly consume
      caffeine and those who do not. METHODS: A double-blind cross-over experimental
      design was used. Data were collected in a research laboratory with a clinical
      exercise testing room. Eight regular caffeine users and eight men who did not
      habitually consume caffeine were studied. Each subject consumed of a beverage
      once with and once without 4.5 mg caffeine/kg fat-free mass added to the drink.
      Following consumption each subject walked at three intensities of exercise (30,
      50, and 70% of VO2peak). Measures of BP were obtained by the auscultatory
      technique. RESULTS: Caffeine consumption resulted in significant increases in
      both systolic BP and diastolic BP at rest and during exercise. The elevation
      during exercise was 7-8 mmHg at all three exercise intensities for systolic BP;
      however, for diastolic BP there was only a significant elevation (4 mmHg) at the
      highest exercise intensity. No differences were noted between those men who
      regularly consume and those who regularly abstain from caffeine. There was a wide
      range in the resting BP response to caffeine (combined SBP and DBP ranged from 10
      39 mmHg) suggesting that there are marked differences in sensitivity to caffeine,
      irrespective of individuals' consumption habits. CONCLUSIONS: Consideration
      should be given to caffeine intake prior to exercise in patients for whom an
      additional increase in BP during exercise would not be desirable.

PMID- 9638034
TI  - Exercise tolerance, body composition and blood lipids in obese African-American
      women following short-term training.
AB  - BACKGROUND: The purpose of this investigation was to examine the exercise
      tolerance, body composition and blood lipids in African-American women,
      possessing greater than or equal to 30% body fat, following six weeks of
      endurance training. METHODS: Oxygen consumption (VO2), central hemodynamics,
      blood lipids, body weight, body fat, and the body mass index of seven subjects
      (21.0 +/- 0.8 yrs) were studied. Heart rate (HR), blood pressure (BP), exercise
      duration, rating of perceived exertion (RPE), blood lactate (bLA) and VO2 were
      obtained in response to a maximal exercise tolerance test on a motorized
      treadmill. Subjects trained three times per week for 50 minutes per session (30
      minutes at 70% maximal oxygen consumption (VO2max). RESULTS: Dependent "t"-tests
      revealed significant (p < 0.05) increases in VO2max, 27%; exercise duration, 31%;
      as well as peak HR, systolic blood pressure (SBP), and bLA. Values for submaximal
      HR, SBP, RPE during the post-training test were lower. In addition, body weight,
      body fat and the body mass index decreased 2.2%, 1.3% and 3.4% respectively.
      There were no changes in blood lipids. CONCLUSIONS: These findings suggest short
      term training at 70% VO2max provides the necessary stimulus for obese women to
      improve exercise tolerance and body composition. However, the training stimulus
      is insufficient to alter lipid profiles.

PMID- 9638035
TI  - Measurement of exercise dependence in bodybuilders.
AB  - OBJECTIVE: The purpose of this study was to explore exercise dependence in
      bodybuilders, and undertake preliminary validation of a measurement instrument.
      EXPERIMENTAL DESIGN: A comparative analysis of self-report indices between
      groups. PARTICIPANTS: Forty-seven bodybuilders, 31 individuals who weight trained
      for general fitness purposes and 24 weightlifters participated in the study.
      MEASURES: Each subject completed the following: demographic information,
      bodybuilding-specific versions of the social identity and exclusivity scales of
      the Athletic Identity Measurement Scale, the physical strength and body
      attractiveness subscales of the Physical Self-Perception Profile, a short form of
      the Marlowe-Crowne Social Desirability Scale, and a 9-item Bodybuilding
      Dependence Scale. RESULTS: Factor analysis on the BDS revealed 3 subscales
      (social dependency, training dependency and mastery) which accounted for 68.4% of
      the variance. Internal consistency was satisfactory for each subscale
      (Chronbach's alpha = 0.76, 0.75 and 0.78 respectively). The BDS social dependency
      and PSPP body attractiveness scores of the bodybuilders were higher than those of
      the weightlifters, whose scores were higher than those of the fitness trainers.
      The bodybuilders scored higher on both AIMS subscales than the other groups. The
      bodybuilders and weightlifters scored higher on PSPP physical strength than the
      fitness trainers. BDS social dependency correlated with both AIMS and both PSPP
      subscales, and BDS training dependency correlated with AIMS exclusivity. All
      three BDS subscales correlated with training frequency. Discriminant analysis
      found the combination of AIMS social identity, BDS social dependency and years
      training experience enabled correct classification of 92% of the respondents.
      CONCLUSIONS: These results support the construct and concurrent validity of the
      BDS social dependency subscale, but do not wholly support the validity of the
      other two subscales.

PMID- 9638036
TI  - Training and injuries amongst elite female orienteers.
AB  - BACKGROUND: A study was carried out on the patterns of injury amongst elite
      female orienteers. METHODS: A retrospective questionnaire was administered which
      contained questions pertaining to training practices such as quality, quantity
      and type. This was followed by a section investigating general to specific injury
      problems, regarding their occurrence and effect on training. Members of various
      national orienteering squads (elite group; n = 19) and competitors of an elite
      level in Great Britain (sub-elite group; n = 9) completed these questionnaires.
      As this was a descriptive study, no intervention was carried out. RESULTS: The
      sub-elite orienteers trained less than the elite during the off-season (p < 0.01)
      but there was no significant difference in the distribution and/or likely cause
      of injuries between the groups. Only 32% of the subjects did their training
      predominantly on the road while the others ran on either off-road terrain or a
      mixture. Injuries occurred in 68% of the respondents. Only 4% of them suffered
      upper body injuries. Ankle injuries were the most common injuries. The proportion
      of injuries to the knee (16%) and ankle (43%) in orienteers was the reverse of
      what is normally found in runners. CONCLUSIONS: Orienteers suffer certain sport
      specific injuries such as ankle sprain. This is likely to be related to their
      training predominantly on rough surfaces.

PMID- 9638037
TI  - Overweight prevalence in persons with Down syndrome.
AB  - Prevalence of overweight among the general population has been reported to be 33%
      for males and 36% for females. We undertook this study to establish overweight
      prevalence data in a cohort with Down syndrome and to stratify the incidence of
      overweight by living arrangement. We measured Body Mass Index (BMI) in 283
      persons with Down syndrome and found a higher prevalence of overweight in this
      group compared to the general population. Individuals with Down syndrome living
      in a family setting had a higher incidence of overweight than did those living in
      a group home setting. Overweight prevalence among persons with Down syndrome
      should be considered a major public health concern that warrants further
      attention from researchers, practitioners, family members, and individuals with
      Down syndrome.

PMID- 9638038
TI  - Neuroleptic-induced dementia documented in four adults with mental retardation.
AB  - This is the first report to my knowledge of neuroleptic-induced dementia in
      adults with mental retardation. Four adults showed full recovery after having
      significant cognitive deterioration that persisted until the offending medication
      was withdrawn. The ages at onset of dementia were 37, 37, 39, and 55 years; the
      duration of dementia ranged from .5 to 2.5 years. Three adults had Down syndrome
      and one had mental retardation due to an unknown cause. The neuroleptic-induced
      dementia occurred while the individuals were on a low dose of either loxapine,
      thioridazine, haloperidol, or pimozide.

PMID- 9638039
TI  - Evaluation of outcomes and cost-effectiveness of a community behavioral support
      and crisis response demonstration project.
AB  - A behavioral support and crisis response demonstration project authorized by the
      Minnesota Legislature in 1992 was evaluated. We described the demonstration
      program, its service users, and satisfaction and concerns with the program of
      service recipients, their families and careproviders, and county case managers.
      We also provided follow-up data on the outcomes of the first year service users
      and gave the service outcomes projected by case managers had the program not been
      established. These projected outcomes were validated by follow-up of a comparison
      group of persons unable to access the program's services. Cost-effectiveness was
      computed from costs of establishing and operating the demonstration program and
      the actual average costs of the services that were projected to otherwise have
      been used.

PMID- 9638040
TI  - Effects of video-based staff training with manager-led exercises in residential
      support.
AB  - The effectiveness of video-based staff training with manager-led exercises in
      improving staff performance in residential support for persons with disabilities
      was examined. Research staff assisted two residential program managers to
      implement staff training in health and safety, basic support, and residential
      support values. Results showed improvement in (a) staff members' washing hands
      when appropriate, (b) wearing gloves when appropriate, and (c) frequency of
      positive interactions with residents. These changes in staff behavior maintained
      over a 6-month follow-up. Following the values training, in one house, brief
      increases were observed in frequency of residents' community activities. These
      changes did not maintain. No improvements in these measures were noted in the
      other house. Implications of these findings for assurance of competent staff
      performance with residents were discussed.

PMID- 9638041
TI  - Employment outcomes for people with severe disabilities: opportunities for
      improvement.
AB  - Supported employment began with a focus on those individuals deemed less likely
      to secure a job in the community: those with severe mental retardation,
      behavioral challenges, and multiple disabilities. The creation of supported
      employment resulted, in part, because of demonstrations of the competence and
      capabilities of these same people previously thought to be unemployable in any
      meaningful sense of the word. However, as supported employment has unfolded,
      those with the most severe disabilities appear to be underrepresented in the
      ranks of those benefitting from supported employment. Although the limited access
      to supported employment by individuals with such labels appears clear, little is
      known about how the employment of those with more severe disabilities compares
      with others in supported employment. This report provides analyses of the
      employment features, support patterns, and outcomes for persons with more severe
      disabilities in supported employment.

PMID- 9638042
TI  - How a regression artifact makes ICFs/MR look ineffective.
AB  - Based on a simple matched-control group quasi-experiment, Conroy (1996) concluded
      that small ICFs for persons with mental retardation have negative quality-of-life
      impacts. Our analysis of Conroy's design suggests, in contrast, that the reported
      effect is a pure regression artifact. The flaw in Conroy's design is selecting a
      control group on the basis of pretest matching. Although selecting a subsample of
      controls by matching on static characteristics such as age or gender can reduce
      the confounding influence of these variables, selection on the basis of pretest
      scores leads invariably to a large, spurious effect. The literature on this issue
      dates back a century, with warnings against pretest matching by Galton,
      Thorndike, McNemar, Stanley, Campbell, Cronbach, and Cook. We reviewed this
      historical literature and then used a Monte Carlo experiment to estimate the
      spurious effect that Conroy would observe from pretest matching alone. The
      magnitude of the artifact is as large as the quality-of-life reduction that
      Conroy attributed to the effects of living in an ICF. We discussed the
      methodological logic involved in matching and the broader policy issues raised by
      this evaluation.

PMID- 9638043
TI  - Break the data-bank with Monte Carlo? Statistical problems in the dispute between
      Conroy (1996) and Crinella, McCleary, and Swanson (1998)
AB  - In drawing entirely different conclusions from the same bank of data, Conroy saw
      consistent evidence favoring the alternative CLAs over the small ICFs in
      Pennsylvania while Crinella et al. found a large regression artifact produced by
      matching the ICF and CLA residents on adaptive behavior scores. Ten areas of
      flawed logic, analysis, and interpretation have undermined both sides of the
      argument. Conroy's matching--which might not have been necessary in the first
      place--does not pose a serious threat of regression artifacts. Because of two
      subtle but fatal errors, the Monte Carlo experiment of Crinella et al. provides
      no important evidence against Conroy's findings. Other problems, however, require
      a small reduction in his pro-CLA results, along with a substantial limit on their
      generalizability.

PMID- 9638044
TI  - The Carrier Advisory Committee five years later.

PMID- 9638045
TI  - Provider sponsored organizations.

PMID- 9638046
TI  - Metastatic basal cell carcinoma of the auricle.

PMID- 9638047
TI  - [Roller-skating injuries].

PMID- 9638048
TI  - [Treatment of aortic aneurysm with endovascular stent graft].

PMID- 9638049
TI  - [Total mesorectal excision in rectal cancer].

PMID- 9638050
TI  - [Introduction of a new surgical technique in rectal cancer].
AB  - Local recurrence rates following surgery for rectal cancer show considerable
      variation in different series, but impressive results (< 4% local recurrences
      after five years) have been presented by surgeons using total mesorectal excision
      as their operative technique. In Norway, local recurrence rates of 30% have been
      reported. Total mesorectal excision was introduced at Ullevaal Hospital in
      January, 1994 following a specific training programme. To enable us to compare
      the results, we followed-up two groups of patients who had undergone surgery for
      rectal carcinoma; one group (76 patients) before the introduction of total
      mesorectal excision and the other (76 patients) after total mesorectal excision
      was introduced. Anastomotic leakages were the main problem in the initial phase,
      but after faecal diversion became routine only one leakage was observed. After a
      median observation time of 28 months we had observed two patients (4.3%) with
      local recurrence in the total mesorectal excision group, and ten (23.8%) in the
      group where total mesorectal excision had not been performed.

PMID- 9638051
TI  - [Endovascular treatment of thoracic aortic aneurysm].
AB  - Two patients with aneurysms of the descending thoracic aorta were treated by
      endovascular technique. One of the patients was also treated for an infrarenal
      aortic aneurysm by open surgery during the same procedure. The other patient had
      chest pain, probably caused by an impending rupture. The procedures were
      performed using fluoroscopy by a C-arm. The thoracic aneurysms were replaced by
      an implant made of polyester where Z-stents had been applied on the inside. The
      prosthesis was mounted on a pusher and advanced through an introducer. When a
      proper position was obtained, the introducer was withdrawn, and the prosthesis
      was deployed immediately below the left subclavian artery. Endovascular treatment
      seems to represent a less traumatic procedure than open surgery. Both operations
      were uncomplicated and both patients were followed up for more than six months.
      No complications were observed. A longer follow-up period is necessary to
      evaluate this treatment fully.

PMID- 9638052
TI  - [Cholesterol values in a cohort of adolescents in Sor Trondelag].
AB  - Over a four-year period total serum cholesterol values were obtained from all 7th
      grade lower secondary school students (age 13) in a municipality in Norway. The
      139 girls included in the survey had a mean value of 4.24 mmol/l (95% CI 4.12
      4.37), and the 160 boys 4.11 mmol/l (95% CI 3.98-4.23), which is slightly lower
      than other Nordic surveys. Some students from one year were also measured in the
      9th and 11th grades. One student was found to have familial hyper
      cholesterolemia, and this value was excluded from the reference material.
      Screening for this disease among students is not recommended.

PMID- 9638053
TI  - [Neuralgic amyotrophy or an isolated lesion of the anterior interosseal nerve?].
AB  - In this article we describe five patients with acute or subacute weakness of
      flexor pollicis longus and flexor digitorum profundus. A possible diagnosis of an
      isolated lesion (entrapment) of the anterior interosseus nerve was considered.
      However, clinical and neurophysiological findings suggested a diagnosis of
      neuralgic amyotrophy. Three patients experienced acute shoulder pain at the
      onset. Sensory loss at the base of the thumb was observed in two patients, and
      two patients were affected bilaterally. All patients had EMG signs of involvement
      outside the anterior interosseus nerve innervation area. Low amplitude sensory
      action potentials were observed in three patients. One patient was operated upon
      and entrapment was not observed during surgery. Reinnervation was not seen after
      five months, but was noted in three patients who were investigated 13, 13.5, and
      30.5 months after the onset. Thus, the prognosis in this unusual form of
      neuralgic amyotrophy seems to be rather good, and the length of time before
      reinnervation supports the theory that the site of the lesion must be located
      proximally, e.g. in the brachial plexus.

PMID- 9638054
TI  - [Postoperative tetanus after gangrenous ileus].
AB  - Tetanus has become an uncommon disease in developed countries. Tetanus is caused
      by exotoxins from the bacteria Clostridium tetani. This microbe, which is
      obligate anaerobe, is present in soil, and animal and human faeces. The condition
      usually appears after contamination of wounds. However, reports have been
      published of tetanus occurring after both acute and selective gastrointestinal
      surgery. We present a case of severe postoperative tetanus in a 57 year-old woman
      who underwent bowel resection after strangulation of the ileum. The patient was
      treated on an intensive care unit and was artificially ventilated for 64 days.
      Seven months later she had fully recovered. Clinical presentation, diagnosis,
      treatment, and complications are discussed in the report. The diagnosis of
      tetanus is made by clinical observation. Nowadays, lack of suspicion of this
      condition may cause delay in administering proper treatment. Women and older men
      are often inadequately immunized. Doctors should therefore examine the
      immunization status of these groups of patients regularly.

PMID- 9638055
TI  - [Iatrogen perforation of the rectum after colon radiography].
AB  - Perforation of the rectum following barium enema is relatively rare, occurring in
      1 of 3,000 procedures. Colorectal perforation is a serious condition and early
      diagnosis is of paramount importance in order to avoid any delay in treating the
      patient. Direct suture of the perforation, lavage, presacral drainage and stomia
      are the preferred methods of primary surgical treatment.

PMID- 9638056
TI  - [Mechanisms behind drug dependence].
AB  - The neurobiological mechanisms involved in the development and maintenance of
      drug dependency are reviewed and discussed. Whereas physical dependency is
      related to abstinence symptoms with a noradrenergic hyperactivity in locus
      ceruleus, motivational dependency is related to euphoria, which correlates with
      dopaminergic activity in the mesolimbic pathway, especially in nucleus accumbens.
      Despite the fact that many addictive drugs are chemically unrelated, they
      increase the extracellular levels of dopamine in nucleus accumbens. This has been
      observed with cocaine, amphetamine, ecstacy, nicotine, opiates, ethanol, and
      cannabinoids. On the other hand, substances like LSD do not appear to influence
      the dopamine level in the mesolimbic pathway. Increasing knowledge about how drug
      abuse modulates signal pathways in discrete parts of the brain gives a new
      insight into the development and maintenance of drug dependency.

PMID- 9638057
TI  - [Hereditary cancer].
AB  - A significant proportion of all cancers is inherited or develops in genetically
      susceptible individuals. An updated overview and tabulations are given on
      inherited cancer, including the monogenic cancer syndromes, cancer caused mainly
      by predisposition in heterozygous carriers for autosomal recessive syndromes, and
      the same of different types of cancers occurring in families exhibiting irregular
      autosomal dominant inheritance. Environmental factors act in concert with
      genetically susceptible genes to cause cancer. A mechanism for the initiation and
      progression of cancer on the cellular level is outlined. The identification of an
      ever-increasing number of cancer-susceptible genes enables the development of new
      genetic tests. Some advantages and problems associated with predictive genetic
      testing for cancer are discussed.

PMID- 9638058
TI  - [Oncogenes--"reckless drivers" on signal pathways controlling cell division].
AB  - Today, about 20 years after the discovery of cellular genes with oncogenic
      potential, we possess substantial knowledge on the regulation of normal cell
      growth and division. At the same time, we have gained insight into the loss of
      growth control which occurs in cancer cells. The following is a brief review of
      the progress made in oncogene research and the knowledge we have gained. It is
      important to stress that our understanding of the cellular and molecular
      mechanisms involved is still in its infancy. However, pieces are being added to
      the puzzle at an increasingly faster pace, primarily because of the progress in
      gene technology during the last two decades. Research methods have been set up to
      allow greater cooperation across disciplinary boundaries, thus increasing the
      speed with which important discoveries occur. A goal for the future will be to
      identify all oncogenes and tumor suppressor genes and elucidate their functions.
      At the same time, one of the major challenges will be to translate the knowledge
      thus gained into the development of more powerful and specific therapeutic
      strategies. As a result of the increasing insight gained by modern oncogene
      research, the need for detailed cancer diagnostics based on molecular genetics
      will increase significantly in the future.

PMID- 9638059
TI  - [Tumor suppressors--genes and proteins].
AB  - Cancer is generally understood to be a genetic disease in the sense that somatic
      mutations are the cause of tumour initiation and development. Our knowledge of
      cancer-associated genes and gene products has evolved mainly over the past 20
      years. The identification and characterization of tumour suppressor genes (TSGs)
      as normal growth-inhibiting or apoptosis-inducing genes have helped us to
      understand how mutations are tumorigenic. Various TSG encoding membrane-, cytosol
      , or nuclear proteins have been identified. Tumor suppressor genes are often
      functionally inactive in cancer cells because of mutations of both parental gene
      copies. Many TSGs are associated with hereditary cancer diseases or syndromes
      caused by the existence of one mutant allele in the germ-line. Individuals who
      carry only one functional gene copy, are therefore at great risk of developing
      cancer. Several TSGs, such as TP53, RB1 and CDKN2A, encode proteins that are
      significant to the cell cycle. TP53 is the most frequently mutated gene in human
      cancer, showing changes in more than 50% of all solid tumours. Both DNA repair
      and apoptosis are stimulated by p53-induced transcription of genes involved in
      the two processes. The characterization of TSGs and their gene products has led
      to the identification of a number of new diagnostic and prognostic molecular
      genetic parameters in oncology. Furthermore, some TSGs are potentially among the
      most promising and important targets for gene therapy in cancer and other
      hyperproliferative diseases.

PMID- 9638060
TI  - [We need a specialty of community and general psychiatry].

PMID- 9638061
TI  - [Migraine and stroke].

PMID- 9638062
TI  - [Medical findings].

PMID- 9638063
TI  - [Hereditary hemochromatosis and use of genetic tests].

PMID- 9638065
TI  - [Physicians and drug industry].

PMID- 9638064
TI  - [What happened with the confidence intervals?].

PMID- 9638066
TI  - Image is all but interpretation is the key.

PMID- 9638067
TI  - The diagnosis of lameness associated with distal limb pathology in a horse: a
      comparison of radiography, computed tomography and magnetic resonance imaging.
AB  - A cadaver limb from an eight-year-old horse with right forelimb lameness that was
      relieved with an intra-articular distal interphalangeal joint block was imaged
      with radiographs, spiral computed tomography (CT) and magnetic resonance imaging
      (MRI). Spiral CT demonstrated several lucencies within the deep digital flexor
      tendon immediately proximal to the navicular bone. On MRI these areas had
      increased signal and there was enlargement of the tendon at this site. Effusion
      in the proximal interphalangeal joint and navicular bursa and thinning of the
      fibrocartilage of the navicular bone were also observed on MRI images. These
      changes were not detected on radiographs. Histopathology confirmed that there
      were focal areas of collagen necrosis within the deep digital flexor tendon with
      thinning and degenerative changes in the fibrocartilage of the navicular bone.

PMID- 9638068
TI  - Isolation and identification of canine matrix metalloproteinase-2 (MMP-2).
AB  - A canine gelatinase, with an apparent molecular mass of 62 kDa in non-reducing
      zymography, is produced by fibroblasts, chondrocytes and a myelomonocytic cell
      line. The enzyme has similar characteristics to human matrix metalloproteinase
      (MMP) 2 and cross-reacts in Western blotting analysis with a sheep polyclonal
      antiserum raised against human MMP-2. The 62 kDa canine protein was purified from
      cell culture media, and the N-terminal amino acid sequence determined following
      blotting on to a polyvinylidene difluoride (PVDF) membrane. The sequence was 87%
      identical to that published for human MMP-2. We therefore consider this enzyme to
      be canine MMP-2.

PMID- 9638069
TI  - Use of recombinant human erythropoietin as adjuvant therapy for blood banking for
      autotransfusion in dogs.
AB  - Recombinant human erythropoietin (rhEPO) has been assessed for its potential
      value as an adjuvant in the banking of blood for autotransfusion in dogs. Twelve
      normal adult dogs were assigned to three groups (saline, iron, and iron plus EPO
      groups). On day 0, day 3, and immediately after each autologous blood donation,
      the first group received normal saline as a placebo, the second group received
      4.1 mgkg-1 of iron (iron chondroitin sulphate), and the third group received 600
      IU kg-1 of rhEPO in combination with 4.1 mgkg-1 of iron. Blood for autologous
      donation equivalent to 10 mL kg-1 was collected from each dog on days 7 and 10.
      The blood was retransfused on day 14 during the removal of an equal volume of
      blood and the effect of the autotransfusion evaluated on day 17. After the
      autologous blood donation, a marked decrease in haematocrit occurred in the
      saline and iron groups. In contrast, the haematocrit remained virtually unchanged
      in the iron plus EPO group indicating the therapeutic effect of rhEPO. The iron
      plus EPO group also maintained a high haematocrit after blood collection if they
      had been autotransfused first. It was concluded that rhEPO is a valuable adjuvant
      in canine blood banking for autotransfusion.

PMID- 9638070
TI  - A study of cattle-to-cattle transmission of Mycobacterium bovis infection.
AB  - Twenty steers, positive to the single intradermal comparative tuberculin test
      (SICTT), were selected from herds with a recent history of Mycobacterium bovis
      infection. Ten steers, negative to SICTT, were selected from herds with no
      history of M. bovis infection and served as in-contact animals. The animals were
      divided into 10 groups, each consisting of two SICTT-positive (reactor) animals
      and one in-contact animal. Each group was housed in an individual loose-box for a
      period of 1 year. Five of the groups were fed a restricted diet for part of the
      experiment. All cattle were slaughtered at the end of the study period and
      examined at post mortem. Transmission of infection to an in-contact animal
      occurred in four of the 10 groups. One of the four in-contact animals, which
      became infected, had a retropharyngeal lymph node tubercle and M. bovis was
      isolated from lymph nodes without visible lesions from the other three. Two of
      the infected in-contact animals without visible lesions did not show any
      detectable cell-mediated immune response. There was no evidence that dietary,
      restriction had any effect on transmission of disease.

PMID- 9638071
TI  - Bovine serum transferrin concentration during acute infection with Haemophilus
      somnus.
AB  - A novel, competitive immunoassay based on time-resolved fluorimetry was
      developed, and used to measure the serum concentration of bovine transferrin
      during acute Haemophilus somnus pneumonia. Upper and lower limits of normality
      were established using serum from healthy cattle (3.72-1.37 mgmL-1). Following
      experimental infection with Haemophilus somnus, transferrin concentration was
      depressed in all calves but recovered to pre-infection levels in groups of calves
      which had either no lesions, or mild lesions at necropsy between 5 and 6 days
      after infection. In a third group, which developed extensive lesions, the
      transferrin concentration remained depressed. Transferrin levels remained within
      the normal range for all calves during the experimental period. Those calves
      which had low transferrin concentrations pre-infection, developed extensive lung
      lesions following experimental infection with Haemophilus somnus.

PMID- 9638072
TI  - Equinins in equine neutrophils: quantification in tracheobronchial secretions as
      an aid in the diagnosis of chronic pulmonary disease.
AB  - Equinins are a closely related group of proteins found in equine neutrophil
      granules. They demonstrate proteinase inhibiting activity restricted to microbial
      proteinase K and subtilisin, and they also possess antibacterial and antiviral
      properties. Antiproteinase K activity was measured in tracheobronchial secretions
      (TBS) of horses with mild (n = 15), moderate (n = 30) and severe (n = 16) chronic
      pulmonary disease, to determine its usefulness as an indicator of severity of
      disease and to measure neutrophil content. Determination of proteinase K
      inhibiting activity was based on a colorimetric assay measuring the suppression
      of 4-nitroaniline liberation from the synthetic substrate succinyl-L-alanyl
      alanyl-alanin-4-nitroanilid, a process mediated by proteinase K. Proteinase K
      inhibiting activity proved to be a valid and simple indicator for assessing
      neutrophil content in TBS and a useful parameter to determine the severity of
      chronic pulmonary disease in the horse.

PMID- 9638073
TI  - Detrimental effects on villus form during conventional oral rehydration therapy
      for diarrhoea in calves; alleviation by a nutrient oral rehydration solution
      containing glutamine.
AB  - This paper examines the possibility that treatment of diarrhoea with conventional
      oral rehydration solutions (ORSs) may be detrimental to villus structure by
      imposing nutrient deprivation and that such detrimental effects may be reduced or
      avoided by using a nutrient ORS. A conventional WHO-type ORS (W) was compared
      with two nutrient solutions (N and G) both containing high glucose concentrations
      and the latter containing glutamine; their effects on enteric structure were
      assessed by morphometric analysis of samples obtained from diarrhoeic calves
      after 96 h treatment. Comparisons were also made with samples from controls and
      diarrhoeic calves at the stage where oral rehydration would have begun in the
      treated groups. As in our previous ORS studies, diarrhoea was induced with
      enterotoxigenic Escherichia coli (09:K30:K99). We measured villus length and
      width, crypt depth and width and calculated villus surface area in proximal, mid
      and distal small intestine (PSI, MSI, DSI), using standard morphometric
      techniques. Proximal and distal spiral colon samples (PC, DC) were examined for
      crypt depth and width; mitoses per crypt were counted in samples from all
      regions. Non-diarrhoeic calves showed the expected gradient of villus length
      through PSI, MSI and DSI, hence data for each region are normalized as a
      percentage of the control value for that region. PSI showed the greatest loss of
      villus length and surface area (50%) with diarrhoea. In MSI and DSI the villus
      loss was greater with solution W and N or G, as were increased mitoses and crypt
      depth. Crypt depth and mitoses also increased in the colon with solution W.
      Colonic crypt width increased with diarrhoea and conventional oral rehydration
      but less so with G; there is reason to believe that such changes have functional
      significance. Crypt changes in colon, MSI and DSI were least with solution G. The
      changes developing in diarrhoeic calves prior to treatment were thus less
      apparent in those treated with a nutritional ORS, particularly if it contained
      glutamine.

PMID- 9638074
TI  - Pharmacodynamics and pharmacokinetics of tolfenamic acid in ruminating calves:
      evaluation in models of acute inflammation.
AB  - Injections of mild irritants intradermally (carrageenan, zymosan and dextran) and
      intracaveally (carrageenan) in a tissue cage model of inflammation were used in
      studies of the pharmacodynamics and pharmacokinetics of tolfenamic acid
      administered intramuscularly in calves. Inhibition of serum thromboxane (TX)B2
      and inflammatory exudate prostaglandin (PG)E2 were used as indicators of the
      magnitude and time course of blockade of cyclo-oxygenase isoforms COX-1 and COX
      2, respectively. Single doses of 2, 4 and 8 mgkg-1 tolfenamic acid partially
      inhibited irritant-induced rises in skin temperature (non-dose dependently) and
      skin oedema (dose-dependently). These doses also markedly inhibited serum TXB2
      synthesis and the duration of inhibition was dose-related. A dose of 2 mgkg-1
      tolfenamic acid also attenuated skin temperature rise over carrageenan-injected
      tissue cages, and markedly inhibited exudate PGE2 synthesis, even though drug
      penetration into both exudate and tissue cage transudate was limited. Tolfenamic
      acid pharmacokinetics were characterized by a relatively short tmax (0.94-2.04
      h), a high estimated Vdarea (1.79-3.20 Lkg-1), an estimated t1/2 beta of 8.01
      13.50 h and Cl beta of 0.142-0.175 Lkg-1h-1. The actions of tolfenamic acid in
      inhibiting PGE2 synthesis and in attenuating two of the cardinal signs of
      inflammation (heat and swelling) suggest that a dosage of 2 mgkg-1 administered
      intramuscularly should be effective clinically as an anti-inflammatory agent.

PMID- 9638075
TI  - Molecular analysis of the virulence determinants of Clostridium perfringens
      associated with foal diarrhoea.
AB  - During an epidemiological study of foal diarrhoea, over half of the cases yielded
      Clostridium perfringens which was significantly associated with disease
      (Netherwood et al., 1996b). However, the association could not be accounted for
      by enterotoxigenic isolates which had a low prevalence (Netherwood et al., 1997).
      Nonetheless, we have hypothesized that the association may be caused by a
      pathogenic sub-population which would be significantly more common amongst C.
      perfringens-positive cases compared with C. perfringens-positive healthy controls
      if it acted as a pathogen when present. Conversely, if foal diarrhoea caused by
      C. perfringens was dependent on a predisposing factor, then such an association
      might not be evident. As a first step to determine if a molecular marker was more
      frequently to be found in C. perfringens-positive cases than controls, we have
      genotyped the study isolates (up to five per foal) by polymerase chain reaction
      (PCR) based on the published gene sequences for the major lethal toxins alpha,
      beta, epsilon and iota as well as for theta toxin, large and small sialidases,
      hyaluronidase and virulence regulation. Isolates of major toxin types B, C, D and
      E, or isolates which were untypeable, were isolated from less than 15% of C.
      perfringens-positive foals and these were not associated with diarrhoea nor were
      they more commonly found in C. perfringens-positive cases. Isolates of type A
      were found in more than 90% of all C. perfringens-positive foals. A number of
      different genotypes were identified by their different patterns of gene
      possession but types without any of the genes for theta toxin, large and small
      sialidases, hyaluronidase and virulence regulation were found in only 10% of
      positive foals. Only type A isolates with all of these genes were associated with
      diarrhoea overall but they were not more commonly isolated from C. perfringens
      positive cases than controls. In conclusion, genotyping by the sequenced
      virulence genes did not identify a marker for a sub-population of C. perfringens
      which may be acting more frequently as a pathogen when present.

PMID- 9638076
TI  - Plasma aspartate aminotransferase and creatine kinase activities in thoroughbred
      racehorses in relation to age, sex, exercise and training.
AB  - In order to investigate the effect of age, sex and month on the response of
      plasma aspartate aminotransferase (AST) and creatine kinase (CK) to exercise,
      blood samples were collected once a month between March and September from a
      group of 40 2- and 3-year-old (2yo and 3yo) thoroughbred racehorses (kept under
      the same managemental regimen) at rest before exercise (PRE) and at 2 (2H) and 24
      h (24H) post-exercise. The absolute change in activities between the 2H and PRE
      samples (2H delta) and the 24H and PRE samples (24H delta) was also calculated.
      Age had a significant effect on all measured and calculated parameters for colts
      (C), apart from 24H delta CK but showed no effect in the fillies (F). Sex only
      had a significant effect in the 3yo in the 2H delta CK. In the 2yo, significant
      effects of sex were found for both CK and AST in the PRE, 2H and 24H samples. The
      effect of month varied according to the classification group with only the 2yoC
      not showing any significant effect on any parameter. Fillies were, in general,
      more likely than colts to show greater than a twofold increase in CK activity at
      2H post-exercise and the number of animals showing such an increase decreased as
      the season progressed. Very little change in AST activities occurred with
      exercise.

PMID- 9638077
TI  - Ultrasonographic examination of the ovine thorax.

PMID- 9638078
TI  - Effect of single and divided dose administration on the pharmacokinetics of
      albendazole in sheep and goat.
AB  - The pharmacokinetics of albendazole were studied in sheep and goats following
      single and divided dose administration at nematocidal and flukicidal dose rates.
      The disposition curves of the metabolites indicated increased uptake of the drug
      both in sheep and goats at divided dose schedules compared to single dose
      administration (P < 0.05). The increased bioavailability of benzimidazole
      anthelmintics in divided dose schedules could improve their efficacy and help in
      extending their lives.

PMID- 9638079
TI  - Gross anatomy of the accessory nerve and vagus nerve of the head and cranial neck
      region in the Bactrian camel.
AB  - Seven heads and necks of Bactrian camels were dissected to investigate the
      origin, course, branches and distribution of the accessory nerve and vagus nerve
      in the cranial cervical region. The spinal root and external branch of the
      accessory nerve were not present, but there was a delicate communicating branch
      between the dorsal root of the first cervical nerve and the root of the vagus
      nerve. The sternocephalic muscle was innervated by the second cervical nerve
      while the brachiocephalic and trapezius muscles were supplied by the sixth and
      seventh cervical nerves. In the head and cranial cervical region of the Bactrian
      camel the vagus nerve gave off the auricular branch, pharyngeal branch, cranial
      laryngeal nerve, a common trunk to the larynx, oesophagus and trachea, and some
      communicating branches connecting with the glossopharyngeal, hypoglossal, first
      cervical nerves and the cranial cervical ganglion.

PMID- 9638080
TI  - Ultrasonographic examination of 12 ovine vaginal prolapses.

PMID- 9638081
TI  - Managed care and unintended pregnancy.

PMID- 9638082
TI  - Adolescent pregnancy prevention in managed care.

PMID- 9638084
TI  - Prevention of sexually transmitted diseases in an era of managed care: the
      relevance for women.

PMID- 9638086
TI  - Correlates and perceived outcomes of four types of employee development activity.
AB  - Participation in 4 different types of development activity was studied in a
      sample of manufacturing employees (N = 1,798). It was found that similar sets of
      variables were linked to greater participation in 3 activities: required training
      courses in work time, work-based development activity in work time, and career
      planning activity in work time or an individual's own time. Three kinds of
      reported benefits were studied, and the occurrence of these benefits was found to
      vary between different types of development activity. Overall job satisfaction
      and organizational commitment were significantly associated with prior
      participation in required training courses and work-based development activity.
      However, voluntary learning in one's own time was completely unrelated to these
      work attitudes.

PMID- 9638087
TI  - Psychosocial factors predicting employee sickness absence during economic
      decline.
AB  - Psychosocial factors such as work characteristics, life events, social support,
      and personality were examined as predictors of the change in medically certified
      sickness absence observed during a period of severe economic decline.
      Longitudinal data, derived from self-reports and register-based information
      relating to 763 local government employees, were collected at 3 points during a 5
      year period: before the economic decline, during the nadir of that decline, and
      immediately after the nadir. After the effects of prior absence and demographic
      and lifestyle variables had been partialed out, the results of multiple Poisson
      regression analyses showed that work characteristics play a major role in
      forthcoming sickness absences. Negative life events and the personality trait
      sense of coherence (in women) also predicted forthcoming absence rate. Social
      support did not relate to absences either in men or in women.

PMID- 9638088
TI  - Gender differences in ethical perceptions of business practices: a social role
      theory perspective.
AB  - This study presents a meta-analysis of research on gender differences in
      perceptions of ethical decision making. Data from more than 20,000 respondents in
      66 samples show that women are more likely than men to perceive specific
      hypothetical business practices as unethical. As suggested by social role theory
      (A. H. Eagly, 1987), the gender difference observed in precareer (student)
      samples declines as the work experience of samples increases. Social role theory
      also accounts for greater gender differences in nonmonetary issues than in
      monetary issues. T. M. Jones's (1991) issue-contingent model of moral intensity
      helps explain why gender differences vary across types of behavior. Contrary to
      expectations, differences are not influenced by the sex of the actor or the
      target of the behavior and do not depend on whether the behavior involves
      personal relationships or action vs. inaction.

PMID- 9638089
TI  - Self-efficacy as a mediator of the relationship between perceived union barriers
      and women's participation in union activities.
AB  - This study investigated the influence of union self-efficacy (expectations of
      success in pursuit of union activities) as a mediator of the relationship between
      perceptions of barriers to union participation and women's participation in union
      activities (N = 89). Perceived barriers were defined in 4 domains (community,
      family, union, work), and self-efficacy was operationalized based on C. Lee and
      P. Bobko's (1994) analysis of self-efficacy measures (self-efficacy magnitude,
      self-efficacy strength). Union self-efficacy was found to mediate the
      relationship between the magnitude of perceived union barriers and the magnitude
      of union participation, although mediation was limited to women with weak union
      self-efficacy. Implications for designing training and intervention programs to
      enhance women's participation in the face of perceived barriers are discussed.

PMID- 9638090
TI  - The way we were: gender and the termination of mentoring relationships.
AB  - The relationship between gender and the termination of mentoring relationships
      was assessed in a matched sample of 142 male and female ex-proteges. Counter to
      prevailing assumptions, when gender differences in rank, salary, tenure, and
      other demographic and organizational variables were controlled, women did not
      differ from men in the number or duration of prior relationships or in their
      reasons for terminating the relationship.

PMID- 9638091
TI  - Theory and configurality in clinical judgments of expert and novice
      psychologists.
AB  - This article shows that in judging the degree of pathology of mental patients,
      expert psychologists, more than novices, assign heavier weight to the more
      pathological information. This difference is explained in terms of the
      professional socialization process of clinical psychologists.

PMID- 9638092
TI  - [Lumbar bone density. Risk factor for vertebral fractures in women].
AB  - BACKGROUND AND OBJECTIVE: The direct connections between a reduction in bone
      density and an increase in the incidence of fractures with increasing age is well
      known. When interpreting bone density measurements the attending physician is
      confronted with an overlap of false-positive and false-negative parameters, as is
      also the case with biochemical data. Aim of this study was to determine, in
      addition to bone density, a fracture threshold, i.e. a value for bone density
      with maximal sensitivity and specificity, in a representative cohort of women.
      PATIENTS AND METHODS: 534 healthy women (mean age 60.9 +/- 8.07, range 40-83
      years), seen in an out-patient osteological clinic between 1993 and 1996 were
      included. After full biochemical investigation to exclude a metabolic bone
      disease, bone density (LBD) of the lumbar vertebrae 1-5 and the number of
      vertebral body fractures were documented, together with age and menopausal
      status. LBD was measured by quantitative computed tomography (qCT), results being
      analysed with the Wilcoxon 2-sample test and logistic regression and assessed by
      receiver operating characteristics (ROC) analysis. RESULTS: None of the women
      with a qCT value over 111 mg/cc had evidence of vertebral fractures. Those with
      values under 60 mg/cc had at least one vertebral fracture (defined as at least
      15% reduction in vertebral body height). There was a highly significant negative
      correlation between age and LBD (r = -0.56; P < 0.0001), as well as between LBD
      and the number of fractured vertebrae (r = -0.58, P < 0.0001). But there was no
      longer any correlation between age and number of vertebral body fractures once
      allowance was made for LBD (r = 0.001, not significant). The least overlap of
      false-positive and false-negative values was at an LBD with qCT values of 102
      mg/cc. CONCLUSIONS: LBD is the determining variable for fracture risk independent
      of age. Despite an overlap of false-positive and false-negative LBD values, the
      probability of fractures can be predicted from bone mineral content.

PMID- 9638093
TI  - [Acute posterior wall infarct after factor VIII concentrate administration to a
      patient with severe hemophilia A].
AB  - HISTORY AND CLINICAL FINDING: A 69-year-old man with severe haemophilia A
      sustained an acute myocardial infarction (MI) after self-administration of 3000
      units factor VIII over 10 min. On admission he had no signs of heart failure.
      INVESTIGATIONS: The ECG showed an acute posterior wall MI. Creatinekinase rose to
      a maximum of 321 U/l with a significant MB proportion. The echocardiogram
      demonstrated hypokinesia of the posterior wall. TREATMENT AND COURSE: After
      initial thrombolysis treatment with a total of 100 mg rtPA according to an
      accelerated scheme coronary angiography, performed because the symptoms
      persisted, revealed two-vessel disease. A subtotal stenosis of the right coronary
      artery was balloon-dilated with good primary results. Regular factor VIII
      substitution was temporarily administered with the aim of initially achieving
      high normal levels of factor VIII activity. CONCLUSION: Factor VIII substitution
      in haemophilia A may promote thrombotic complications. Thrombolytic treatment and
      balloon angioplasty of acute MI can be successfully performed even in patients
      with severe haemophilia A.

PMID- 9638094
TI  - [Sicca symptoms and hearing loss in Behcet's syndrome].
AB  - HISTORY AND ADMISSION FINDINGS: A 39-year-old woman sustained an irreversible
      hearing loss in the left ear, followed 6 months later by a left facial paresis.
      Oral aphthous ulcers frequently recurred with fever of up to 39.5 degrees C. Her
      general condition was noticeably poor. INVESTIGATIONS: An inflammatory disease
      was suggested by an increased erythrocyte sedimentation rate (70/100 mm),
      leucocytosis (18,500/microliter), decreased haemoglobin (10.2 g/l) and leftward
      shift of the neutrophil granulocytes. Diagnostic tests for an infectious,
      autoimmune or haemato-oncological disease were negative. TREATMENT AND COURSE:
      Antibiotic and antimycotic treatment failed to bring lasting improvement.
      Thrombophlebitis and venous thrombosis developed in both upper limbs and acute
      episcleritis (scleritis) in the left eye. Behcet's disease with oral, ocular,
      neurological, cutaneous and vascular involvement was diagnosed and treated with
      chlorambucil (variable dosage around 7 mg/d orally), with rapid regression of
      symptoms. 3 months later joint pains set in, and another 18 months later she
      developed sicca symptoms (xerostomia with dry eyes): both responded to
      symptomatic treatment. CONCLUSION: The combination of loss of hearing, sicca
      syndrome and Behcet's syndrome has not been previously reported.

PMID- 9638095
TI  - [Extragastric side effects of non-steroidal antirheumatic agents ].

PMID- 9638096
TI  - [Adjuvant treatment for colon carcinoma. Results and perspectives].

PMID- 9638097
TI  - [Antihypertensive therapy using a combination of angiotensin 1 receptor
      inhibitors with angiotensin-converting enzyme inhibitors].

PMID- 9638098
TI  - [Diagnosis and therapy of primary stomach lymphoma].

PMID- 9638099
TI  - ["Bull-neck" in HIV-positive patients: result of therapy?].

PMID- 9638100
TI  - [Ambulatory therapy concepts for a "forgotten disease:" tuberculosis].

PMID- 9638101
TI  - Management of the third stage of labor.

PMID- 9638102
TI  - Risk of stroke in patients with carotid bruits.

PMID- 9638103
TI  - Calcium channel blockers and cardiovascular complications in hypertensive
      diabetics.

PMID- 9638104
TI  - Finasteride for BPH.

PMID- 9638105
TI  - Potentiation of warfarin by acetaminophen.

PMID- 9638106
TI  - Warming bupivacaine for intradermal anesthesia.

PMID- 9638107
TI  - Lack of efficacy of cisapride and nizatidine in dyspepsia.

PMID- 9638108
TI  - Identifying cardiac risk in patients with atypical chest pain.

PMID- 9638109
TI  - Smoking cessation and weight gain.
AB  - Cigarette smokers have a lower average body weight than nonsmokers, and the
      cessation of smoking is associated with weight gain. Although this weight gain
      does not offset the health benefits of smoking cessation, it is frequently a
      source of concern for smokers planning to quit. The objective of our review was
      to estimate the risk and duration of weight gain after cessation of smoking to
      help physicians in counseling concerned smokers. We reviewed the literature by
      doing a MEDLINE search using key words for articles on the changes in body weight
      after smoking cessation. The retrieved data indicated that (1) the risk of weight
      gain is highest during the 2 years immediately following smoking cessation, and
      declines thereafter; (2) on average, sustained quitters gain about 5 to 6 kg in
      weight; (3) physical exercise, older age, higher baseline body mass index, and
      lower rates of smoking attenuate the degree of weight gained after smoking
      cessation; and (4) the evidence regarding the permanence of the expected weight
      gain is conflicting.

PMID- 9638110
TI  - The rising tide of hospitalism: evidence-based or anecdote-based medicine?

PMID- 9638112
TI  - The Spiritual Involvement and Beliefs Scale. Development and testing of a new
      instrument.
AB  - BACKGROUND: Spirituality is receiving greater attention in the medical
      literature, especially in the family practice journals. A widely applicable
      instrument to assess spirituality has been lacking, however, and this has
      hampered research on the relationship between spirituality and health in the
      clinical setting. METHODS: A new instrument, called the Spiritual Involvement and
      Beliefs Scale, was designed to be widely applicable across religious traditions,
      to assess actions as well as beliefs to address key components not assessed in
      other available measures, and to be easily administered and scored. The
      instrument is a questionnaire containing 26 items in a modified Likert-type
      format. Following careful pretesting, the instrument was administered to 50
      family practice patients and 33 family practice educators. The validity and
      reliability of the instrument were then evaluated. RESULTS: By several measures,
      instrument reliability and validity are very good, with high internal consistency
      (Cronbach's alpha = .92); strong test-retest reliability (r = .92); a clear four
      factor structure; and a high correlation (r = .80) with another established
      measure of spirituality, the Spiritual Well-Being Scale. CONCLUSIONS: The
      Spiritual Involvement and Beliefs Scale (SIBS) appears to have good reliability
      and validity. Compared with other instruments that assess spirituality, the SIBS
      has several theoretical advantages, including broader scope, use of terms that
      avoid cultural-religious bias, and assessment of both beliefs and actions. More
      testing is underway to further assess its usefulness.

PMID- 9638111
TI  - Treatment of acute bronchitis in adults. A national survey of family physicians.
AB  - BACKGROUND: The purpose of this study was to determine how family physicians in
      the United States treat acute bronchitis in an otherwise healthy adult. METHODS:
      A 33-item questionnaire on the diagnosis and treatment of acute bronchitis was
      mailed to a random sample of 500 physicians who are members of the American Board
      of Family Practice. RESULTS: Thirty-two of the 500 sampled physicians could not
      be located by mail; 265 of those who received the questionnaire responded. The
      response rate was 57% (265/468). Sixty-three percent of responding physicians
      indicated that antibiotics are their first choice of treatment for the otherwise
      healthy, nonsmoking adult with acute bronchitis. The decision to use antibiotics
      as the first choice of treatment did not vary by physician's sex, age, years in
      practice, practice location, practice type, or percentage of HMO patients. Only
      6% of responding physicians reported using beta 2 agonist bronchodilators as
      their first choice of treatment. Physicians in this study stated that they
      prescribe an antibiotic 75% of the time in treating nonsmoking patients with
      acute bronchitis (first choice or otherwise). If the patient is a smoker,
      physicians reported that they prescribe antibiotics 90% of the time (F = 110.25;
      df = 1; P > .0001). Physicians reported that for patients who smoke it takes
      longer for coughs to totally resolve and longer for them to return to a normal
      activity level than for nonsmokers. CONCLUSIONS: Family physicians report that
      antibiotics are their most common treatment for acute bronchitis in the otherwise
      healthy adult. Previous clinical trials have shown only marginal improvement in
      symptoms when patients with this condition are treated with an antibiotic. With
      antibiotic resistance emerging as a major global health problem, it is essential
      that other methods of treatment be evaluated.

PMID- 9638113
TI  - Criteria used by clinicians to differentiate sinusitis from viral upper
      respiratory tract infection.
AB  - BACKGROUND: Acute sinusitis and upper respiratory tract infections (URIs) share
      many common symptoms and signs. Objective criteria have been identified that are
      valid for distinguishing between these two clinical problems. The objective of
      this study was to determine how often clinicians use these validated criteria and
      how often they rely on clinical cues that are less valuable for differentiating
      sinusitis from URI. METHODS: We performed a retrospective review of 734 patients
      with a diagnosis of acute sinusitis (n = 367) or URI (n = 367) at a family
      practice residency training site over a 3-year period. Charts were reviewed to
      ascertain patient demographics, past history, current symptoms, physical
      findings, and treatment prescribed. RESULTS: Patients with sinusitis were likely
      to be older, female, smokers, have a history of allergic rhinitis, and have
      longer symptom durations. Complaints of sinus pressure or discolored nasal
      discharge and the finding of sinus tenderness were strongly associated with the
      diagnosis of sinusitis. In multivariate analysis, eight factors were
      independently associated with the diagnosis of sinusitis. Four clinical cues
      alone (sinus tenderness, sinus pressure, postnasal drainage, and discolored nasal
      discharge) were highly associated with the diagnosis of sinusitis and explained
      60% of the variation in the diagnosis between sinusitis and URI. CONCLUSIONS:
      Physicians tend to rely on four factors to differentiate sinusitis from URIs.
      Only one of these has been shown to be a reliable predictor of acute sinusitis.
      This use of unreliable criteria may lead to misdiagnoses and inappropriate
      prescriptions for antibiotics.

PMID- 9638114
TI  - Screening men for partner violence in a primary care setting. A new strategy for
      detecting domestic violence.
AB  - BACKGROUND: Health care domestic violence initiatives have given little attention
      to screening men for violent behavior toward their partners. We conducted this
      study to assess whether men would answer questions about partner violence in a
      health care setting, to estimate the prevalence of violent behavior in male
      primary care patients, and to identify characteristics associated with violent
      behavior. METHODS: We used an anonymous written survey at three family medicine
      clinics. The survey instrument included the Conflict Tactics Scale to measure
      aggressive and violent behavior. Standard questions assessed demographic
      variables and health behaviors. RESULTS: Three hundred seventy-five men were seen
      during the study. Of these, 317 (85%) participated and 237 met inclusion
      criteria. Thirty-two men (13.5%, 95% confidence interval (CI), 9.1-17.9)
      disclosed physical violence toward their partner in the previous 12 months. Ten
      men (4.2%, 95% CI, 3.7-4.8) reported severe violence. Men with increased alcohol
      consumption, depression, or history of abuse as children were more likely to
      report violent behavior. Presence of all three variables resulted in a
      probability of violence of 41%, compared with a baseline probability of 7% if no
      risk factors were present. CONCLUSIONS: Primary care physicians should consider
      screening male patients for aggressive behavior toward their intimate partners.
      Physicians should be especially cognizant of this possibility in men who are
      depressed, heavy alcohol users, or were childhood victims of abuse.

PMID- 9638115
TI  - Physician employment status and practice patterns.
AB  - BACKGROUND: Many physicians today are employed by another physician, group,
      hospital, HMO, or other organization. However, the differences in the
      characteristics, practice patterns, and patient outcomes of self-employed and
      employed physicians are not well understood. METHODS: The practices of 108
      community family physicians in northeast Ohio were assessed using a multimethod
      cross-sectional design. Physician characteristics were assessed by questionnaire.
      Direct observation of 3536 consecutive patient visits was used to measure time
      use and the delivery of preventive services recommended by the US Preventive
      Services Task Force. Patient satisfaction was assessed with the Medical Outcomes
      Study (MOS) 9-item Visit Rating Form. RESULTS: Employed physicians were more
      likely to be female, in group practice, work fewer hours, and see fewer patients.
      Job satisfaction was similar between the two groups, but employed physicians
      reported greater satisfaction with leisure and family time. Employed physicians
      spent more time per patient visit, scheduled a larger percentage of well-care
      visits, and were more likely to refer to specialists. Employed physicians also
      spent a greater proportion of their patients' visit time performing history
      taking and eliciting family information, and a lesser proportion of time on
      physical examination, planning treatment, providing health education, and
      chatting. Recommended screening and health habits counseling preventive services
      were more likely to be delivered by employed physicians. Patient satisfaction was
      similar for the two groups. CONCLUSIONS: Primary care physician characteristics
      and practice patterns differ by employment status. The consequences of the trend
      toward a largely employed physician workforce as reported in this study should be
      carefully considered.

PMID- 9638116
TI  - Chronic appendicitis: does it exist?
AB  - The typical presentation of acute appendicitis is well known. A few patients,
      however, have had an atypical clinical course suggestive of recurrent appendiceal
      inflammation, which has been confirmed by appendectomy. Therefore, in the
      evaluation of a patient with abdominal pain, a history of similar episodes should
      not preclude a diagnosis of appendicitis.

PMID- 9638117
TI  - Misoprostol in obstetrics and gynaecology--unregistered, dangerous and essential.

PMID- 9638118
TI  - Heart scanner--who's between a rock and a hard place?

PMID- 9638119
TI  - Solid science and hard logic--the rock on which good treatment is based.

PMID- 9638121
TI  - Hypertension care at a Cape Town community health centre.
AB  - OBJECTIVES: To describe the demographic profile of hypertensive patients and the
      quality of care for hypertension at a Cape Town community health centre (CHC).
      DESIGN: Prospective, descriptive study. SETTING AND SUBJECTS: Medium-sized CHC,
      attended by 1,098 hypertensive patients during a 1-year period from 1 January
      1992. OUTCOME MEASURES: Default rate--proportion of due visits not attended. Loss
      to follow-up--proportion of patients persistently defaulting or not responding to
      recall. Frequency of blood pressure measurement--per 12 due visits. Compliance-
      proportion of patients collecting > or = 75% of antihypertensive drugs. Blood
      pressure control--mean blood pressure of aggregated readings; and proportion
      controlled (< 160/95 mmHg) on the basis of all blood pressure readings and mean
      blood pressures of individual patients with two or more readings during the study
      period. RESULTS: More than half (51.6%) of the hypertensive patients were aged >
      or = 65 years; 81.7% were female. The default rate was between 11.9% and 19.4%.
      Compliance was high (76.9%). Loss to follow-up was 8.1%. Blood pressure was
      recorded a mean of 4.0 times per 12 due visits. There were no significant gender
      differences with regard to these measures. Mean blood pressure was 158.3/89.6
      mmHg. Over half (56.7%) of all individual readings over the year were
      uncontrolled and 51.4% of patients were found to be uncontrolled when categorised
      by their mean blood pressure. Control was significantly poorer among women > or =
      65 years. CONCLUSION: We found better compliance, more frequent blood pressure
      measurement, and lower defaulting and loss to follow-up compared with previous
      South African studies in similar settings. Despite this, blood pressure control
      was mediocre. Possible explanations for this are discussed. The low proportion of
      male hypertensives attending the CHC suggests that the accessibility or
      acceptability of care is poor for this group. The study illustrates the potential
      for research in this setting and for the use of computers to monitor the quality
      of primary care.

PMID- 9638122
TI  - Improving cost-effectiveness of hypertension management at a community health
      centre.
AB  - OBJECTIVES: To describe the pattern of prescribing for hypertension at a
      community health centre (CHC) and to evaluate the impact of introducing treatment
      guidelines and restricting availability of less cost-effective antihypertensive
      drugs on prescribing patterns, costs of drug treatment and blood pressure (BP)
      control. DESIGN: Before/after intervention study. SETTING: Medium-sized CHC in
      the Cape Flats area of Cape Town. SUBJECTS: 1,084 hypertensive patients attending
      the CHC, who had at least two prescriptions for antihypertensive drugs during a 1
      year period starting on 1 January 1992. INTERVENTIONS: 1. Implementation of
      stepped-care guidelines for hypertension, specifying treatment with more cost
      effective drugs and minimising drug treatment. 2. Reducing availability for
      routine prescribing by CHC doctors of 10 less cost-effective antihypertensive
      drugs or drug combinations. OUTCOME MEASURES: 1. Mean number of drugs prescribed
      per patient. 2. Proportion of prescriptions for: each major class of
      antihypertensive drug; restricted availability and freely prescribable drugs; and
      more and less cost-effective drugs. 3. Mean monthly cost of drugs prescribed per
      patient. 4. Mean blood pressure and proportion of BP readings controlled (<
      160/95 mmHg) or uncontrolled (> or = 160/95 mmHg). RESULTS: A mean of 1.7 active
      drugs was prescribed per patient per visit. The most frequently prescribed drugs
      were thiazide-like diuretics (44.8%), centrally acting agents (28.4%) and b
      blockers (13.2%). Mean monthly drug costs per patient decreased significantly by
      R1.99 (24.2%) from R8.24 to R6.25 between the first and last prescription for
      each patient (exclusive of any reduction due to withdrawal of treatment). This
      was attributable to reduced prescribing of more expensive drugs withdrawn from
      routine use and a 51.1% increase in prescribing of the most cost-effective drugs.
      The overall annual cost-saving of the changes in prescribing for this CHC are
      estimated at R75 150. Blood pressure control did not change significantly.
      CONCLUSION: The pattern of changes in prescribing and drug costs was consistent
      with a causal effect of the interventions. The study demonstrates the potential
      for improving cost-effectiveness of hypertension care in primary care in South
      Africa and the potential for research in this setting.

PMID- 9638123
TI  - Survival of children in Cape Town known to be vertically infected with HIV-1.
AB  - OBJECTIVE: To determine the survival patterns of children in Cape Town known to
      be vertically infected with HIV. DESIGN: Retrospective record review of children
      diagnosed with symptomatic HIV infection during the period 1 December 1990-31 May
      1995. SETTING: Hospitals in the Cape Town metropolitan area. PATIENTS: 193
      children were known to be vertically HIV-infected. HIV diagnosis was based on the
      following criteria: two positive HIV enzyme-linked immunosorbent assays (ELISAs)
      in children older than 15 months and a positive ELISA together with a positive
      polymerase chain reaction (PCR) in younger children. The mothers of the children
      were known to be HIV-positive. On the basis of the presenting clinical findings
      children were assigned to a disease severity category (A, B or C) according to
      the Centers for Disease Control and Prevention (CDC)'s 1994 revised
      classification system for HIV infection in children. OUTCOME MEASURES: Survival
      was analysed according to the Kaplan-Meier method. Survival time was defined as
      the length of time between clinical diagnosis of HIV and death or last contact
      with the health services. Mortality risk in relation to specific variables at
      diagnosis such as age and clinical manifestations was determined by calculation
      of odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: The median age
      at diagnosis was 5 months; 72% of children were aged less than 1 year at
      diagnosis. According to the CDC clinical classification, 47 (24%) fell into
      category A, 111 (58%) into category B and 35 (18%) into category C. Of the 193
      patients 85 (44%) were alive at the time of review, 65 (34%) had died and 43
      (22%) were lost to follow-up. Risk of death was significantly associated with age
      less than 6 months (OR 4.7, CI 2.1-10.3) and severe disease, i.e. CDC category C
      (OR 2.7; CI 1.1-6.9) at time of diagnosis. The median survival for all the
      children from time of diagnosis was 32 months. Infants diagnosed before 6 months
      of age had significantly shorter median survival (10 months) compared with 36
      months for those diagnosed at 7-12 months of age. For the children over the age
      of 12 months the cumulative proportion surviving at 48 months was 78%. Children
      with severe disease (category C) had a median survival of 21 months,
      significantly lower than that in category B (32 months). For the children in
      category A the cumulative proportion surviving at 48 months was 66%. CONCLUSION:
      The median survival of children with HIV was 32 months from time of diagnosis,
      and survival was influenced by age and disease severity.

PMID- 9638124
TI  - Electron beam computed tomography for the diagnosis of cardiac disease.
AB  - Electron beam computed tomography (EBCT) of the heart is a new modality which
      will alter the way cardiology is practised. It allows for the detection of early
      coronary artery disease (CAD) in asymptomatic individuals, regardless of their
      level of risk as assessed by traditional risk factor analysis. Compared with risk
      analysis based on risk factors alone, an assessment which also utilises
      quantitative measurements of coronary artery plaque by EBCT allows for more
      precise determination of the need for medical therapy. Non-invasive intravenous
      contrast EBCT coronary angiography can identify significant obstructive CAD, and
      should reduce the need for conventional coronary angiography. Incorporation of
      EBCT into routine medical practice is more cost-effective than other modalities
      currently available. This paper reviews relevant original articles on EBCT and
      preventive cardiology published in peer-reviewed medical journals, and assesses
      the implications of EBCT for preventive cardiology.

PMID- 9638125
TI  - Enterococcal endocarditis--a case treated with teicoplanin and amoxycillin.
AB  - The study aimed to determine the antibacterial therapy effective in the cure of
      endocarditis caused by Enterococcus faecalis resistant to clinically achievable
      levels of vancomycin. Isolation of the causative enterococcus had been achieved
      by direct inoculation of the resected valve into the culture medium in theatre.
      The patient was known to have had an aortic valve defect since childhood and had
      recently undergone splenectomy following trauma. Blood cultures were negative
      prior to valve replacement. A perivalvular abscess was noted at operation. In
      vitro minimal bactericidal results and serum activity were the basis of the
      postoperative choice of drugs. The minimal bactericidal level of teicoplanin was
      250 micrograms/ml and that of amoxycillin 64 micrograms/ml. Neither is achievable
      with the advocated dosage. A combination of these two cell-wall-active agents
      successfully eliminated the infection. Acting at two different sites in the
      synthesis of the bacterial cell wall, teicoplanin and amoxycillin were found to
      be bactericidal in vitro at the trough levels of the antibiotics in the serum.
      The patient recovered fully.

PMID- 9638126
TI  - Limb reduction anomaly after failed misoprostol abortion.

PMID- 9638127
TI  - A peripheral hospital can be fulfilling--for staff and patients alike.

PMID- 9638128
TI  - The ethics of physician-assisted suicide and euthanasia.

PMID- 9638129
TI  - Heart scanner 'min dae'?

PMID- 9638131
TI  - Training of rural doctors--a means of enhancing the effectiveness of referrals.

PMID- 9638133
TI  - Therapeutic application of organ electrodermal diagnostics for pain.

PMID- 9638134
TI  - Caring for babies who survive an abortion attempt--an ethical dilemma.

PMID- 9638135
TI  - Late terminations of pregnancy.

PMID- 9638137
TI  - Complete nucleotide sequence of wheat yellow mosaic bymovirus genomic RNAs.
AB  - The complete sequences of wheat yellow mosaic bymovirus (WYMV) RNA1 and RNA2 were
      determined. RNA1 is 7636 nucleotides long [excluding the 3'-poly(A)], and codes
      for a 269 kDa polyprotein of 2,404 amino acids which contains the capsid protein
      (CP) at the C terminus and seven putative nonstructural proteins. RNA2 is 3,659
      nucleotides long and codes for a polyprotein of 904 amino acids which contains a
      28 kDa putative proteinase and a 73 kDa polypeptide. These functional proteins
      are arranged as in RNA1 and RNA2 of barley yellow mosaic bymovirus (BaYMV).
      Comparisons with the sequence reported for the 3' half of RNA1 of wheat spindle
      streak mosaic bymovirus (WSSMV) from Southern France show that WYMV and WSSMV
      have a similar genetic organization. However, WYMV and WSSMV share only 77% amino
      acid sequence identity in their deduced CPs in spite of their close serological
      relationship, and 74% nucleotide sequence identity in their 3' non-coding
      regions. Thus, the sequence data indicate that WYMV and WSSMV are not strains of
      the same virus, which has long been suggested, but are distinct virus species
      within the genus Bymovirus of the family Potyviridae.

PMID- 9638138
TI  - Hepatitis C virus infection and mutations of mannose-binding lectin gene MBL.
AB  - We assessed the genetic polymorphism of mannose-binding lectin (MBL) in 93
      patients with chronic hepatitis C (45 responders and 48 nonresponders to
      interferon) and 218 healthy controls. Mutant allele was identified only at codon
      54 (Gly-->Asp), leading to three genotypes (54 m/m, 54 W/m, and 54 W/W).
      Frequency of 54 m/m was significantly lower in interferon-responders (2.2%),
      compared to those in nonresponders (14.6%) and controls (10.6%): p < 0.05. Our
      results suggest that homozygous carriage of the variant allele of codon 54 of MBL
      may predict poor response to interferon in chronic hepatitis C patients.

PMID- 9638139
TI  - Two avian H10 influenza A virus strains with different pathogenicity for mink
      (Mustela vison).
AB  - We compared two strains of avian influenza A viruses of subtype H10 by exposing
      mink to aerosols of A/mink/Sweden/3,900/84 (H10N4) naturally pathogenic for mink,
      or A/chicken/Germany/N/49, (H10N7). Lesions in the respiratory tract during the
      first week after infection were studied and described. Both virus strains caused
      inflammatory reactions in the lungs and antibody production in exposed mink but
      only mink/84 virus was reisolated. The lesions caused by mink/84 virus were more
      severe with higher area density of pneumonia, lower daily weight gain, and more
      virus in the tissues detected by immunohistochemistry. The results indicate that
      mink/84 (H10N4), but not chicken/49 virus (H10N7), established multiple cycle
      replication in infected cells in the mink.

PMID- 9638140
TI  - Experimental induction of mucosal disease: consequences of superinfection of
      persistently infected cattle with different strains of cytopathogenic bovine
      viral diarrhea virus.
AB  - Mucosal disease (MD) can be induced in cattle persistently infected with
      noncytopathogenic bovine viral diarrhea virus (ncp BVD virus) by superinfecting
      them with antigenically related cytopathogenic (cp) BVD virus strains. While some
      of these animals succumb to early onset MD after 2 to 3 weeks post infectionem
      (p.i.), others only react by producing neutralizing antibodies against the cp BVD
      virus strain and may develop late onset MD after longer incubation periods. The
      aim of this study was to determine if an increasing degree of antigenic homology
      between the ncp and the superinfecting cp BVD virus strains as determined by
      their comparative reactivity with E2 glycoprotein specific monoclonal antibodies
      (mabs) increases the probability of inducing early or late onset MD,
      respectively. For this, each two of eight clinically healthy animals from the
      same herd and persistently infected with the same ncp BVD viruses were
      superinfected with four different cp BVD virus strains. As only two of these
      animals developed late onset MD, one animal from a different herd that developed
      early onset MD was included in the study. Besides clinical observation and
      testing for antibody production, virus isolation and characterization of the cp
      BVD virus isolates were performed. The results indicate that antigenic similarity
      as determined by comparative mab analysis alone is not sufficient to allow
      prediction of the outcome of the disease.

PMID- 9638141
TI  - Defective RNA packaging is responsible for low transduction efficiency of CAEV
      based vectors.
AB  - Replication defective retroviral vectors are regularly used for transfer and
      expression of exogenous genes into dividing cells and in animals. Since
      lentiviruses are able to infect terminally differentiated and non-dividing cells,
      their use to produce replication defective vectors may overcome this limitation.
      We developed two replication-defective lentiviral vectors based on the genome of
      Caprine Arthritis Encephalitis Virus (CAEV). The first vector (pBNL2) carries the
      neo and lacZ marker genes. Neo gene is expressed from a genomic RNA and lacZ gene
      from a subgenomic RNA. The second vector (pCSHL) carries a single fusion gene
      encoding both phleomycin resistance and beta-galactosidase activity. Replication
      competent CAEV was used as helper virus to provide the viral proteins for
      transcomplementation of these vectors. Our data demonstrated that the genomes of
      both vectors were packaged into CAEV virions and transduced into goat synovial
      membrane cells following infection. However, the vector titers remained 3 to 4
      logs lower than those of CAEV. Further analysis showed a lack of accumulation of
      unspliced pBNL2 RNA into the cytoplasm of producer cells resulting in the
      packaging of pBNL2 sub-genomic RNA only. In contrast, RNA produced from pCSHL
      vector was correctly transported to the cytoplasm and more efficiently packaged
      than the pBNL2 sub-genomic RNA as revealed by slot-blot and quantitative RT/PCR
      analyses. However this higher packaging efficiency of pCSHL genome did not result
      in a higher transduction efficiency of lacZ gene.

PMID- 9638142
TI  - Genetically determined resistance to flavivirus infection in wild Mus musculus
      domesticus and other taxonomic groups in the genus Mus.
AB  - Inherited resistance to flaviviruses in laboratory mice is a rare trait conferred
      by an autosomal dominant gene (Flvr). To provide information on genetic
      resistance to flaviviruses in wild mice, we analysed (i) wild M. m. domesticus
      trapped in Australia, and (ii) mice representing other species and subspecies in
      the genus Mus. Mice were screened for resistance relative to C3H/HeJ mice by
      intracerebral challenge with Murray Valley encephalitis virus or yellow fever
      virus, and breeding studies were undertaken to identify inherited resistance
      factors. Widespread flavivirus resistance was demonstrated in Australian M. m.
      domesticus. A single, autosomal dominant Flvr-like gene appeared to be primarily
      responsible, but there was some evidence for additional inherited resistance
      factors. Flavivirus resistance was also identified in other taxonomic groups, and
      a genetic basis for this resistance was demonstrated in M. m. musculus (Skive),
      M. spretus, and M. spicilegus. Interestingly, M. m. musculus (CZI-O) were more
      susceptible than C3H/HeJ mice. Our findings show that genetic resistance to
      flaviviruses is common in divergent taxonomic groups in the genus Mus, suggesting
      that the trait has an ancient evolutionary origin, but whether flavivirus
      resistance genes have an anti-viral role or serve some other function is unknown.

PMID- 9638143
TI  - Fas antigen expression and apoptosis of lymphocytes in macaques infected with
      simian immunodeficiency virus strain mac.
AB  - To investigate the role of apoptosis in the pathogenesis of HIV infection we used
      macaques infected with simian immunodeficiency virus (SIV) as a primate model and
      examined the characteristics of the apoptosis of lymphocytes in SIV mac-infected
      macaques. In vitro apoptosis was more strongly induced in peripheral blood
      mononuclear cells (PBMC) from SIV mac239-infected macaques than those from
      uninfected controls. We found that the frequency of Fas antigen-positive cells
      was higher in PBMC from SIV mac-infected macaques than from uninfected controls,
      and in vitro apoptosis of PBMC was suppressed by an inhibitor of the interleukin
      1 beta converting enzyme (ICE) family proteases. In biopsied lymph nodes, the
      number of apoptotic nuclei in T cell-dependent areas was higher in SIV mac
      infected macaques than in uninfected controls. A higher number of apoptotic
      nuclei in lymph nodes of SIV mac-infected macaques was observed in the stage of
      persistent general lymphadenopathy than in those with AIDS-related complex, while
      there was no significant difference in the extent of apoptosis of cultured PBMC
      among the SIV mac-infected macaques. These results suggest that in vitro
      apoptosis is mediated by the Fas/Fas ligand and ICE system and that apoptosis in
      lymph nodes may be more closely related to the stage of SIV mac infection than is
      that of cultured PBMC.

PMID- 9638144
TI  - Genetic targets for the detection and identification of Venezuelan equine
      encephalitis viruses.
AB  - Rt-PCR probes targeted to different gene sequences of VEE (Venezuelan equine
      encephalitis) virus strain TC-83 were assessed for their sensitivity, specificity
      and non-specific cross-reactivity. A generic VEE virus amplimer
      (VNSP4F2/VNSP4R2), targeted against nsP4 was identified, which was sensitive
      (detected at least 10 pfu) and robust (worked over a wide range of salt
      concentrations and annealing temperatures). An E2 amplimer designed against TC
      83, (VE2F/VE2R), identified VEE strains TRD (1AB), P676 (1C), 3880 (1D)
      Everglades (2) vRNA whilst a second E2 primer pair designed against strain
      68U201, (68UF/68UR), identified all the remaining VEE viruses in the sero
      complex. This would suggest that the VEE virus E2 gene can be sub-divided at the
      genetic level into two separate groups making it a useful target for
      differentiation of serosubtypes 1 and 2 from the other VEE virus subtypes. Using
      a panel of amplimers targeted to different VEE genes and strains it was possible
      to distinguish between most of the serotypes, but most importantly, we were able
      to detect the epizootic strains TRD and P676 as well as other VEE viruses
      implicated in human disease (sero-subtypes 1D and 1E).

PMID- 9638145
TI  - Identification and characterization of the Spodoptera littoralis
      nucleopolyhedrovirus type B lef-3 gene.
AB  - We have identified a gene from the Spodoptera littoralis nucleopolyhedrovirus
      type B (SpliNPV-B) with several characteristics that suggest that it is
      homologous to the lef-3 genes of the Autographa californica and Orgyia
      pseudotsugata NPVs (AcMNPV and OpMNPV, respectively). The SpliNPV-B lef-3 gene
      was mapped between 43.6 and 45.5 map units of the SpliNPV-B genome. Northern blot
      analysis showed that SpliNPV-B lef-3 was expressed as a 1.6 Kb transcript at 5 h
      post infection (p.i.), reached high levels at 24 h p.i., and remained highly
      expressed at 56 h p.i. Transcription of SpliNPV-B lef-3 initiated at two distinct
      sites downstream from a TATA-box motif and terminated 25 nucleotides downstream
      from the translation stop site of the putative LEF-3 polypeptide. The 5'
      boundaries of lef-3 promoter elements were investigated by transient expression
      assays, which revealed that the major components of the lef-3 promoter are within
      a 183 base pair region upstream of the distal transcription initiation site.
      Transfection of SpliNPV-B infected Sf9 cells with anti-sense oligonucleotides
      designed to inhibit LEF-3 expression resulted in substantial reduction of viral
      DNA replication, suggesting that the role of SpliNPV-B lef-3 may be similar to
      that of AcMNPV and OpMNPV lef-3 genes, which are essential for viral DNA
      replication.

PMID- 9638146
TI  - Evidence that whitefly-transmitted cowpea mild mottle virus belongs to the genus
      Carlavirus.
AB  - Two strains of whitefly-transmitted cowpea mild mottle virus (CPMMV) causing
      severe (CPMMV-S) and mild (CPMMV-M) disease symptoms in peanuts were collected
      from two distinct agro-ecological zones in India. The host-range of these strains
      was restricted to Leguminosae and Chenopodiaceae, and each could be distinguished
      on the basis of symptoms incited in different hosts. The 3'-terminal 2500
      nucleotide sequence of the genomic RNA of both the strains was 70% identical and
      contains five open reading frames (ORFs). The first three (P25, P12 and P7)
      overlap to form a triple gene block of proteins, P32 encodes the coat protein,
      followed by P12 protein located at the 3' end of the genome. Genome organization
      and pair-wise comparisons of amino acid sequences of proteins encoded by these
      ORFs with corresponding proteins of known carlaviruses and potexviruses suggest
      that CPMMV-S and CPMMV-M are closely related to viruses in the genus Carlavirus.
      Based on the data, it is concluded that CPMMV is a distinct species in the genus
      Carlavirus.

PMID- 9638147
TI  - Characterisation of an avian influenza A virus isolated from a human--is an
      intermediate host necessary for the emergence of pandemic influenza viruses?
AB  - The partial sequencing of the internal and the neuraminidase genes of isolate
      268/96 obtained from a woman with conjunctivitis showed all seven to have closest
      homology with avian influenza viruses. The entire nucleotide sequence of the
      haemagglutinin gene of 268/96 had close, 98.2%, homology with an H7N7 virus
      isolated from turkeys in Ireland in 1995. This appears to be the first reported
      case of isolation of an influenza A virus from a human being infected as a result
      of direct natural transmission of an avian influenza virus from birds.

PMID- 9638148
TI  - The roles of vif and ORF-A genes and AP-1 binding site in in vivo replication of
      feline immunodeficiency virus.
AB  - To examine the in vivo roles of auxiliary genes and regulatory elements of feline
      immunodeficiency virus (FIV), the provirus load in various tissues of cats
      infected with each of the mutant viruses (delta vif, delta ORF-A and delta AP-1)
      was studied. Although all mutant viruses could infect various tissues, provirus
      loads in various tissues especially those in cats infected with delta vif virus
      were lower than those with the wild-type virus. Our results indicate the
      significance of vif and ORF-A genes and AP-1 binding site of FIV for efficient
      viral replication and full pathogenicity in cats.

PMID- 9638149
TI  - Effects of GB virus-C/hepatitis G virus on hepatitis B and C viremia in multiple
      hepatitis virus infections.
AB  - We found that patients with dual HBV and GBV-C/HGV infection had comparable serum
      HBV DNA positivity and mean virus concentration compared with age-matched HBV
      carriers, and those with triple infection had a significantly lower HBV DNA
      positivity. Serum HCV RNA positivity and mean virus titer were similar between
      HCV carriers with or without GBV-C/HGV co-infection, and those with GBV-C/HGV co
      infection seemed to have a lower serum ALT level. These data suggest that GBV
      C/HGV infection exerts no significant suppression on levels of chronic hepatitis
      B or hepatitis C viremia.

PMID- 9638150
TI  - Detection of Epstein-Barr virus infection in the epithelial cells and lymphocytes
      of non-neoplastic tonsils by in situ hybridization and in situ PCR.
AB  - Non-neoplastic tonsils were analyzed for detection of Epstein-Barr virus (EBV)
      positive cells by in situ hybridization and in situ PCR. EBV-encoded small
      nuclear RNA 1(EBER1)-positive cells were found in 28.2% of the tonsils and were
      evenly localized in the extrafollicular area and within germinal centers. Latent
      membrane protein 1 (LMP1)-positive cells were also dispersed in the
      extrafollicular and germinal center. Using in situ DNA-DNA hybridization, the EBV
      positive signals were observed in the upper epithelial cell layers of the
      tonsils. In addition, in situ PCR detected EBV DNA-positive cells in the lower
      epithelial cell layers and lymphoid cells.

PMID- 9638151
TI  - Nucleotide sequence of the gene encoding the RNA polymerase and the 3' non-coding
      region of a bovine enterovirus Japanese isolate: rapid synonymous substitutions
      between European and Japanese strains.
AB  - The nucleotide sequences of the genome RNA encoding the RNA polymerase and the 3'
      non-coding region (NCR) of bovine enterovirus (BEV) serotype I Japanese isolate,
      MZ468, were determined. The genetic distance between the two BEV serotype I
      strains, MZ468 and VG-5-27, was calculated by pairwise comparison of nucleotide
      sequences. The synonymous substitution rate was high (1.40 x 10(-2)/site/year),
      and of the same order as those of influenza virus HA, HIV-1 gag and env, and
      enterovirus 70 VP1 genes.

PMID- 9638152
TI  - Turnover of hepatitis C virus genotypes in hemodialysis patients.
AB  - Hepatitis C virus (HCV) genotypes were determined in hemodialysis patients with a
      high prevalence and incidence of infection. A change of HCV genotype was observed
      in 6/14 follow-up samples analyzed 13 and 21 months later. The appearance and
      disappearance of HCV genotypes may be due to either genotype-specific
      intermittent viremic status or viral interference.

PMID- 9638153
TI  - A proposal for a new (third) genus within the family Adenoviridae.
AB  - This article presents a proposal for the establishment of a new adenovirus genus
      to accommodate certain bovine, ovine, and avian adenoviruses with special
      characteristics which differentiate them from members of the existing genera
      Mastadenovirus and Aviadenovirus. This proposal has been developed from earlier
      versions with advice from the Adenovirus Study Group of the International
      Committee on Taxonomy of Viruses (ICTV).

PMID- 9638154
TI  - [A truly useful law (shall we call it Cardinal Law?)].

PMID- 9638155
TI  - [Villous-lipomatous proliferation of synovial membrane of the knee (lipoma
      arborescens). Magnetic resonance findings].
AB  - PURPOSE: We reviewed the imaging patterns of the villous-lipomatous proliferation
      of the knee synovial membrane (lipoma arborescens), with special reference to the
      role of MRI in the diagnosis of this rare condition. MATERIAL AND METHODS: 1994
      to 1996, we examined four patients, none of them with a history of knee trauma.
      The clinical picture was characterized by moderate and painful suprapatellar
      swelling in three cases and by moderate suprapatellar swelling alone in one case.
      All patients were examined with conventional radiography and MRI; two were
      submitted to US and two to CT. The diagnosis of lipoma arborescens was suggested
      on the basis of imaging patterns and then confirmed by histologic findings.
      RESULTS: Conventional radiography showed a roughly oblong slim opacity in the
      suprapatellar recess in all cases; the joint space was always preserved. US
      showed a villous lesion surrounded by fluid, but provided no specific data on its
      nature. CT and MRI not only provided better location and morphologic detailing
      and showed the relationships with articular structures better, but also permitted
      the direct identification of the fat nodules within the abnormal synovial
      reaction. CONCLUSION: We stress the role of MRI in suggesting the correct
      diagnosis of lipoma arborescens, as it was subsequently confirmed in our series
      by histologic findings. In fact, fat-suppression sequences, after T1-weighted SE,
      can typify fat tissue.

PMID- 9638156
TI  - [Computerized tomography assessment of replacement of the cruciate ligaments of
      the knee].
AB  - January, 1993, to December, 1995, we examined with CT 44 patients submitted to
      surgical replacement of knee cruciate ligaments, namely 18 anterior cruciate
      ligaments (ACL) and 6 posterior cruciate ligaments (PCL). ACL was replaced with a
      patellar tendon graft (Eriksson technique) in 23 cases and with a semitendinous
      graft (Lindemann-Bousquet technique) in 7 cases. The autologous new ligament
      appeared as a laminar structure of intermediate density. The tendon had been
      covered with a synthetic lining (Leeds-Kejo) in 10 of the above cases, while the
      new ACL graft was completely synthetic in 8 cases, which synthetic allografts
      appeared hyperdense relative to autologous new ligaments. PCL replacement had
      been performed with Augustine technique (patellar tendon graft in a tibial
      tunnel) in 3 cases, with Hughston technique (medial gastrocnemius graft in a
      medial condylar tunnel) in 2 cases and with a synthetic graft (Gore-tex) in 1
      case. Twelve of 38 new ACLs were injured (7 Eriksson, 3 Lindemann-Bousquet and 2
      synthetic grafts): the injured new ligament was enlarged and hypodense, or
      involved in atrophic absorption. The new ligament was partially calcified in one
      of the 3 patients with PCL replacement with a patellar tendon graft (Augustine
      technique). The bone bract was dislocated in the intercondylar notch in a patient
      submitted to Hughston surgery because of proximal disinsertion of the new
      ligament. The Gore-tex new PCL was sinuous in the proximal tract, with intra
      articular calcified loose bodies. CT adequately depicted surgical results and
      diagnosed the new ligament injuries and other articular abnormalities. MRI is
      currently the gold standard in the multiplanar studies of the postoperative knee,
      but CT can be confidently used to identify ligament injuries and intra-articular
      calcified loose bodies.

PMID- 9638157
TI  - [Deglutition in patients treated with reconstructive laryngectomy].
AB  - INTRODUCTION: We stress the importance of dynamic radiologic studies of
      swallowing in the patients submitted to reconstructive laryngectomy. MATERIAL AND
      METHODS: January, 1989, to December, 1996, we examined 36 patients submitted to
      reconstructive laryngectomy, namely cricohyoidoepiglottopexy in 34 cases,
      cricohyoidopexy in 1 case and Guerrier's cricohyoidoepiglottopexy in 1 case.
      Dynamic radiologic studies were performed with fluoroscopic videorecording (Sony
      U-Matic RM 580) from an X-ray unit. The study was performed with the patients
      standing or sitting, initially acquiring AP and LL fluoroscopic images of the
      oropharyngeal region at rest and during swallowing. The patients then swallowed 2
      boluses of 5 ml liquid (60%) and semiliquid (250%) barium. When aspiration was
      suspected, we began with a 2-ml bolus. RESULTS: The patients were grouped by
      symptoms: group A patients had no symptoms, group B patients had dysphagia and
      group C patients presented aspiration. The functional changes were: reduced
      pharyngeal contraction, reduced epiglottis deflection, reduced hyoid bone
      elevation, aspiration, altered upper esophageal sphincter function. The organic
      alterations were: parapharyngeal diverticulum, pharyngeal stenosis, posterior
      pharyngeal wall introflexion. Three group A patients had severe posterior
      pharyngeal wall introflexion, 4 had marked retention and 2 of them presented
      postswallowing aspiration. Two group B patients had major retention, 1
      cricopharyngeal incoordination, 3 posterior pharyngeal wall introflexion, 2 a
      pseudodiverticulum and 2 a luminal stenosis. Seven group C patients had
      intraswallowing and 3 postswallowing aspiration. CONCLUSION: The
      videofluorographic identification of organic and functional complications,
      sometimes unknown in asymptomatic patients, is useful for therapy and suggests
      the speech specialist the best compensatory mechanism to improve the patients'
      swallowing and consequently their quality of life. Moreover, videofluorography of
      swallowing is a very useful tool in the follow-up, to monitor treatment outcome
      after rehabilitation.

PMID- 9638158
TI  - [Is mammography useful in the detection of breast cancer in women 35 years of age
      or younger?].
AB  - Breast cancer in women 35 years old or younger is unusual. It accounts for 1-3.6%
      of all breast cancers but is the leading cause of cancer mortality in women 15-35
      years old. The diagnostic delay, with T2 or more advanced cancer at clinical
      presentation, is due to the patient's age and the opinion of low mammographic
      reliability for cancer diagnosis in this age group. To assess the usefulness of
      mammography in breast cancer patients aged 35 years or younger, we reviewed the
      clinical, mammographic and histologic data of 65 cancers collected in 7 breast
      diagnosis and counseling centers in Lombardy. Fifty-three patients (81.5%) were
      referred for a palpable breast mass, which was a T2 or more advanced cancer in 23
      cases. Mammography showed malignant patterns (spiculated opacities, clusters of
      microcalcifications, casting, branching and ductal type calcifications) in 31
      patients (47.7%). Mammography was not definitive but correctly suggested further
      examinations in 30 women and it had only 4 false negatives. Ultrasonography
      performed in 43 patients was negative in 3 (7%), pathologic and pathognomonic for
      cancer in 27 (62.8%) and pathologic but not indicative of malignancy in 13
      (20.2%). The cytologic or histologic diagnosis of breast cancer was made under US
      guidance in 24 cases. In women aged 35 years or younger mammography was effective
      in identifying breast cancers; US and fine-needle aspiration biopsy (FNAB)
      complete mammography. We believe that mammography can be a valuable screening
      tool in young women at high risk for breast cancer because of family history.

PMID- 9638159
TI  - [Angiography compared to high resolution magnetic resonance and digital
      angiography in atherosclerosis of the iliac-femoral arteries].
AB  - INTRODUCTION: Magnetic Resonance Angiography (MRA) potentials in all vascular
      districts have been largely applied also to peripheral vessels, where however
      there is no agreement as to the best type of sequence. We investigated the
      sensitivity, specificity and diagnostic accuracy of 2D TOF travel-sat MRA in the
      study of iliac-femoral artery stenoses. The gold standard was digital subtraction
      angiography (DSA). MATERIAL AND METHODS: Twenty patients (14 men and 6 women,
      mean age: 65 years with suspected atheromasic disease were examined. Diagnostic
      MRA and DSA were carried out within 48 hours of each other. A super-conductive 1
      T magnet (Siemens Impact) and a body coil were used. 2D TOF travel-sat sequences
      were carried out with the following parameters: FA 40 degrees, TR 31 ms, ST 10
      mm, overlap 1 mm, MA 128 x 512. The images acquired on the axial plane were
      postprocessed with MIP on the z axis from -15 degrees to 15 degrees. Two
      different radiologists evaluated MRA and DSA images and graded the stenoses on a
      multiple choice card: 1) negative, 2) 1-40%, 3) 41-70%, 4) 71-99%, 5) occlusion.
      RESULTS: MRA diagnosed 90 positives and 110 negatives: 60 were true positives, 92
      true negatives, 30 false positives and 18 false negatives. MRA overestimated 8
      cases and underestimated 4 cases. DSA findings were negative in 122 cases and
      positive in 78 cases: 4 grade 2, 10 grade 3, 28 grade 4 and 36 grade 5. Relative
      to DSA, MRA sensitivity, specificity and diagnostic accuracy were 72%, 75% and
      74%, respectively; MRA diagnostic accuracy, sensitivity and specificity in
      hemodynamically severe stenoses (> 71%) were 80%, 78% and 71.8%, respectively.
      CONCLUSION: Our study confirms the usefulness of 2D TOF travel-sat MRA in the
      study of iliac-femoral stenoses.

PMID- 9638160
TI  - [Stenosis-occlusion of the carotid bifurcation. Angiography with MR and contrast
      media versus digital angiography].
AB  - PURPOSE: To evaluate the comparative sensitivity, specificity and diagnostic
      accuracy of contrast enhanced magnetic resonance angiography (CE MRA) and digital
      subtraction angiography (DSA) in the study of carotid bifurcation stenoses.
      MATERIAL AND METHODS: Twenty-three patients with suspected cerebrovascular
      insufficiency by carotid stenosis were examined with CE MRA and DSA within 24
      hours of each other. A 1.5 superconductive unit (Signa, General Electric) was
      used for CE MRA; fast spoiled gradient echo recalled (SPGR) images were acquired
      on the coronal plane 12 s after contrast medium injection, with the following
      parameters: TR/TE/FA 8/1/60, MA 256 x 128, NEX 1, FOV 18 x 13, slices/slab 28,
      slice thickness 1 mm, TA 32 s. The images were postprocessed with the maximum
      intensity projection (MIP) and the targeted MIP algorithms. A Siemens Politron
      1000 VR unit was used for DSA examinations. RESULTS: DSA diagnosed 21 true
      positives, namely 4 grade II, 4 grade III, 10 grade IV and 3 grade V stenoses. CE
      MRA scored 100% in stenosis identification and grading, accurately diagnosing all
      the true negatives and the true positives and was always in agreement with DSA as
      to stenosis site. CONCLUSION: CE MRA can be considered the technique of choice to
      study stenosis occlusion in the epiaortic vessels, because it permits a rapid
      panoramic study of the neck vessels and accurate stenosis grading with similar
      patterns to those of DSA. Thus, CE MRA appears to be a valid alternative to DSA.

PMID- 9638161
TI  - [Radiologic assessment of transpyloric spread of gastric carcinoma].
AB  - PURPOSE: We report on our personal experience with the radiologic and CT
      demonstration of the traspyloric duodenal spread of gastric carcinoma, whose
      relative frequency and prognostic value are recent literature data. MATERIAL AND
      METHODS: In the last 4 years we submitted to double contrast studies of the upper
      gastrointestinal (GI) tract 49 gastric carcinoma patients with antrum
      involvement. Twenty-one cases were staged with CT performed with gastric water
      distension, pharmacological hypotonia and dynamic contrast agent perfusion.
      Finally, 41 patients underwent surgical treatment. RESULTS: Radiologic evidence
      of transpyloric gastric carcinoma spread was found in 6 cases; CT, performed in 5
      of them, was always in agreement. Five of 6 positive cases had surgical
      confirmation while one lesion was unresectable. No radiologic or CT false
      negatives were found among the remaining 36 surgical patients. Barium studies
      showed irregular antral lumen narrowing, rigid, open and eccentric pyloric
      channel, duodenal bulb deformity and irregular thickening. CT demonstrated antrum
      infiltration along the two gastric curvatures and the tumor spread to the
      duodenal cap. CONCLUSION: Antral cancer transpyloric spread is more frequent than
      previously reported and its presence should not exclude a carcinomatous process.
      Double contrast barium studies are a valuable tool in the demonstration of this
      spread, showing good correlation with CT staging findings.

PMID- 9638162
TI  - [Nine consecutive patients with gallstone ileus. Personal experience].
AB  - INTRODUCTION: Gallstone ileus is a mechanical obstruction of the gastrointestinal
      tract caused by the impaction of one or more gallstones within the bowel lumen.
      The insidious clinical presentation and the lack of specific signs of biliary
      disease are responsible for the delayed preoperative diagnosis which leads to an
      overall mortality rate of 15%. MATERIAL AND METHODS: A series of 9 consecutive
      patients (7 women and 2 men, age ranging from 17 to 83 years), with surgically
      proved gallstone ileus, was retrospectively reviewed: the authors report the
      radiologic procedures performed preoperatively and the diagnostic findings. Plain
      abdominal radiographs were performed in 4 of 9 patients, abdominal US in 4 and CT
      in 7 patients. All radiologic examinations were retrospectively reviewed by all
      authors independently, to recognize the different signs of gallstone ileus.
      RESULTS: The signs of Rigler's triad (small bowel obstruction, ectopic gallstones
      and air in the biliary tree) were observed on plain abdominal films in two cases,
      and ectopic gallstones and pneumobilia in two cases. The ectopic gallstones and
      the small bowel obstruction were demonstrated on abdominal US images in three
      cases. Rigler's triad was identified on abdominal CT images in 4 cases, while two
      findings (small bowel obstruction and ectopic gallstones) were observed in three
      cases. CONCLUSIONS: When the bowel is obstructed by a radiopaque calcified stone,
      plain radiographs and US of the abdomen are usually enough to diagnose gallstone
      ileus and no further studies are required.

PMID- 9638163
TI  - [Prostatic volume: suprapubic versus transrectal ultrasonography in the control
      of benign prostatic hyperplasia].
AB  - INTRODUCTION: During the follow-up of benign prostatic hypertrophy, the urologist
      needs the repeated evaluation of the gland size to monitor the effectiveness of
      drug treatment. We investigated the comparative adequacy of transabdominal and
      transrectal US for prostatic measurements, to possibly replace the gold standard
      transrectal examination with cheaper, easier and less invasive transabdominal
      studies. MATERIAL AND METHODS: February, 1994, to May, 1996, we submitted 196
      patients to prostate US, with a transabdominal convex probe and a transrectal
      biplanar probe. The three prostatic diameters were measured and prostatic volume
      and height calculated. RESULTS: The transverse diameter was the same (+/- 5%) in
      31.6% of cases, but transabdominal US overestimated it in 41.8% and
      underestimated it in 26.5% of cases. The AP diameter was the same in 33.1% of
      cases, but trans-abdominal US overestimated it in 15.3% and underestimated it in
      51.5% of cases. The cranio-caudal diameter was the same in 25.5% of cases, but
      transabdominal US overestimated it in 59.1% and underestimated it in 15.3% of
      cases. Consequently, the volume calculated with transabdominal US was the same
      (+/- 15%) in 27.5% of cases, overestimated in 45.9% and under-estimated in 26.5%
      of cases; prostatic weight rates were about the same. CONCLUSIONS: Prostatic
      volume and weight measured with transabdominal US are overestimated in about 50%
      of cases and are the same (+/- 15%) in about 27% of cases only. Therefore,
      transabdominal US appears less reliable than transrectal US for prostatic
      measurements and the latter technique remains the gold standard to monitor drug
      treatment effectiveness in benign prostatic hypertrophy follow-up.

PMID- 9638164
TI  - [Incidence and functional role of antithyroid antibodies in hyperthyroidism].
AB  - INTRODUCTION: We report our personal experience in patients with biochemical
      hyperthyroidism and no nodules, studying the correlations between antithyroid
      autoantibodies titers, thyroid function and clinical symptoms. MATERIAL AND
      METHODS: We examined 93 patients (13 men and 80 women, mean age: 44.6 years,
      range: 25-68 years) referred for suspected hyperthyroidism. Thyroid 99mTc
      scintigraphy was performed and the 20 minutes' uptake index (UI) calculated: all
      these patients had a scintigraphic pattern of normal or enlarged thyroid with
      homogeneous radiotracer uptake. The presence and titer of antiperoxidase (TPO)
      and anti-TSH receptor antibodies (TRAB), FT3, FT4, TSH were assayed. Based on the
      results, the patients were divided into 4 subgroups: A (high TRAB/high TPO, no.
      17), B (low TRAB/high TPO, no. 15), C (high TRAB/low TPO, no. 35), D (low
      TRAB/low TPO, no. 26). The incidence of hyperthyroidism symptoms was 94% in Group
      A, 40% in Group B, 89% in Group C, 50% in group D. RESULTS: UI significantly
      correlated with FT3 (p < .001), FT4 (p < .01) and TRAB (p < .01) titers. FT3 and
      UI average values were significantly higher in Group A and Group C patients (high
      TRAB) than in Group B and Group D patients (low TRAB) (p < .01); these parameters
      were significantly higher also in Group A than in Group B patients (p < .05 for
      FT3 and p < .03 for UI, respectively). Mean intergroup TSH values did not differ
      (p = ns) and anti-TPO antibodies did not correlate with FT3, FT4 and TSH titers.
      CONCLUSIONS: UI behaved as a good marker of hyperthyroidism in all patients and
      TRAB correlated well with organ function and the clinical picture; however, about
      18% of patients exhibited no antibody production. No correlation was found
      between TPO and thyroid function. The lack of antithyroid antibodies seems to
      indicate a better clinical course for hyperthyroidism. The patients without TRAB
      and/or with high anti-TPO titers may follow different clinical courses and need a
      regular follow-up.

PMID- 9638165
TI  - [Ultrasonography, with Doppler color, and cytologic correlations in Plummer's
      disease].
AB  - PURPOSE: We carried out a retrospective study to assess the different B-mode and
      color Doppler features of Plummer's disease and to compare them with cytologic
      findings. MATERIAL AND METHODS: One hundred and eighty autonomous nodules were
      studied with B-mode US. Mean patient age was 55 years for women and 56 years for
      men. Twenty-seven patients were also submitted to color Doppler US. Forty-nine
      autonomous nodules were also submitted to cytologic examination by fine needle
      aspiration (FNA). RESULTS: The most frequent US pattern was a hypoechoic solid
      nodular lesion (59.8%), while 45.6% of the nodules exhibited a mixed US pattern.
      No mixed areas were found in 100% of the nodules in the patients under 20 and
      over 60. In contrast, various degrees of mixed areas were found in the patients
      20-59 years old, with the highest rate (24.9%) in the 40-49 age range and the
      lowest rate (6.2%) in the 20-29 age range. The mixed areas were most frequently
      correlated with bigger nodules and the toxic phase. Calcifications were found in
      4.3% of the partially autonomous nodules in 4.1% of the pretoxic nodules and in
      8.6% of the toxic nodules. Color Doppler US showed rich internal and peripheral
      vascularization (pattern A) in 74.1% of the nodules and a mostly perilesional
      flow (pattern B) in 25.9% of the cases. Pattern A prevailed in the toxic phase
      (75%), while pattern B in the partially autonomous nodules (85.7%). Simple
      hyperplasia was the most frequent (63.3%) cytologic feature in the solid nodular
      lesions, while bleeding (10.2%) was typical of the mixed anechoic nodular
      lesions. Cytologically undifferentiated lesions were found in the toxic phase of
      Plummer's disease (50%). DISCUSSION: Solid lesions in Plummer's disease are
      characterized by hyperplasia, while the diagnosis of hemorrhagic pseudocyst is
      typical of mixed lesions. CONCLUSIONS: Color Doppler US provides data on the
      functional phase of Plummer's disease and is a very useful tool to monitor
      medical treatment results; moreover, it permits to characterize the lesions with
      the richest vascularization, avoiding inadequate cytologic sampling.

PMID- 9638166
TI  - [Magnetic resonance in the study of suprarenal neoplasms. Qualitative and
      quantitative analysis of signal intensity].
AB  - INTRODUCTION: Magnetic Resonance Imaging (MRI) has been proposed as the
      diagnostic technique of choice to characterize adrenal tumors. However, the
      results of the current studies are controversial. MATERIAL AND METHODS: Forty
      nine patients with unilateral adrenal masses were submitted to MRI for lesion
      characterization on the basis of MR signal intensity. Cytology and/or histology
      demonstrated 14 pheochromocytomas (pheos), 11 adenomas, 3 cysts, 2 myelolipomas,
      4 carcinomas, 3 metastases and 1 fibrosarcoma; a clinical diagnosis of adenoma
      was made in the remaining 11 patients. MR studies were performed using spin-echo
      (SE) sequences with T1 (TR/TE = 600/17 ms) and T2 (TR/TE = 2000/15-90 ms)
      weighting. T1-weighted images were also acquired after Gadolinium-DTPA (Gd-DTPA)
      administration. MR studies were integrated with in- and out-of-phase (TR/TE =
      100/4-6 ms) chemical-shift (CS) sequences. MR signal intensity (SI) was analyzed
      qualitatively and quantitatively; MR results were correlated with tumor type and
      hormone secretion. RESULTS: The qualitative analysis of T2 images showed high
      signal intensity in the majority (80%) of adrenal lesions (14 pheos, 12 adenomas,
      3 cysts, 2 myelolipomas and 8 malignancies). The quantitative analysis of post-Gd
      DTPA T1 images permitted to distinguish adenomas, cysts and myelolipomas from
      pheos and malignancies. The qualitative analysis of post-Gd-DTPA T2 and T1 images
      permitted to distinguish pheos and cysts from adenomas and malignancies (p <
      .05); however, pheos and cysts as well as adenomas and malignancies were not
      differentiated. MR SI was similar in secreting and nonsecreting adenomas from
      both a qualitative and a quantitative viewpoints. CS MRI permitted to distinguish
      adenomas (decreased signal intensity on out-phase relative to in-phase images)
      from other benign and malignant lesions (no signal change from out-phase to in
      phase images). CONCLUSIONS: The qualitative analysis of MR SI on conventional T1
      and T2 images does not permit to differentiate adrenal masses. The qualitative
      evaluation of T1 images after Gd-DTPA administration, the quantitative analysis
      and CS sequences are technical options improving lesion characterization.

PMID- 9638167
TI  - [Subtraction magnetic resonance angiography. Description of a new technique].

PMID- 9638168
TI  - [Intra-arterial antiblastic treatment of breast carcinoma].
AB  - PURPOSE: To report our personal experience with the locoregional treatment of
      breast cancer. MATERIAL AND METHODS: Eighteen patients aged 33-67 years (mean: 54
      years) were treated with 31 sessions of intra-arterial antiblastic infusion, 5 of
      them for neoadjuvant purposes (Group 1), 5 for palliation in unresectable tumors
      (Group 2) and 8 for cutaneous recurrences after mastectomy (Group 3). RESULTS:
      2/5 CR and 3/5 PR were obtained in Group 1; 2/5 lesions were made resectable and
      3/5 RP obtained in stage III or unresectable lesions (Group 2). Finally, 3/8 CR,
      3/8 PR, 1/8 SD and 1/8 PD were observed in Group 3. An objective response
      according to WHO criteria was demonstrated in 15/18 cases (88%). We had no post
      treatment hematologic complications, but one patient presented focal subcutaneous
      sclerosis and one cutaneous necrosis. CONCLUSIONS: The morphological efficacy of
      intraarterial antiblastic infusion in our series was similar to that of other
      series. No definitive conclusions can be drawn yet about clinical results and
      long-term survival. This poorly invasive and low risk procedure, which should be
      combined with other treatments, permits to reduce the extent of surgery and to
      treat skin recurrences.

PMID- 9638169
TI  - [Multiple bilateral biopsy of the prostate].
AB  - INTRODUCTION: Transrectal guided biopsy is the method of choice to detect
      carcinoma of the prostate. Systematic bilateral biopsies have been recently
      introduced in clinical practice because they provide valuable information about
      the local staging of the cancer and better representation of the actual Gleason
      grade of the whole tumor. The purpose of this study is to assess the frequency of
      neoplastic lesions in prostatic areas with normal structure at US and rectal
      examination and to identify, if possible, some criteria to be used in the
      selection of patients for random biopsies. MATERIAL AND METHOD: Systematic
      bilateral prostatic biopsies were performed in 155 patients with elevated
      prostate specific antigen (PSA) values, not exceeding 40 ng/mL and with suspected
      neoplastic unilateral lesion at rectal examination or US. All patients with
      bilateral or diffuse nodules were not included in this analysis. Three random
      biopsies for every side of the gland were performed using a 16-18 gauge tru-cut
      needle. A direct biopsy of the hypoechoic nodule or area was always performed.
      All specimens results were correlated with PSA and PSA density values obtained
      before biopsy. RESULTS: Systematic biopsy identified cancers in 53/155 patients
      (34.19%). Of 53 cases, 35 (66%) had unilateral prostatic carcinoma and 18 (34%)
      had bilateral cancer. The final diagnosis was benign prostatic lesion in the
      remaining 102 patients (benign prostatic hyperplasia, nonspecific granulomatous
      prostatitis, chronic prostatitis). Dividing all the patients into main groups on
      the basis of pathologic findings (benign, unilateral and bilateral carcinoma)
      there was a statistically significant difference of PSA values between the 3
      groups. CONCLUSIONS: Our observations confirm the utility of systematic US-guided
      biopsies in the detection of tumors in normal appearing areas at US and
      transrectal examination, but the clinical utility of this approach needs further
      confirmation. Additional data on cancer volume, Gleason grade, capsular
      infiltration, lymph node metastasis and long term survival must be evaluated with
      large number of patients. In our experience PSA values can be used as a criterion
      to select the patients to submit to this technique to provide useful,
      preoperative information suspected prostatic malignancy.

PMID- 9638170
TI  - [Diagnostic imaging of the salivary glands in patients undergoing radiotherapy of
      head and neck neoplasms].
AB  - INTRODUCTION: Radiotherapy of head and neck cancers changes the shape and
      function of the salivary glands included in the treated region. We investigated
      the morphological and functional alterations in the major salivary glands in 15
      patients treated with radiotherapy for head and neck cancers (total dose: 55-66
      Gy). MATERIAL AND METHODS: All the patients underwent B-mode and power Doppler
      US, CT and 99mTC salivary scintigraphy, before, at the end, and 60-80 days after
      radiotherapy. RESULTS: At the end of treatment, US showed irregular margins and
      inhomogeneous parenchymal echogenicity in 13 parotid and in eight submandibular
      glands. Doppler US showed of focal hyperemia and focally decreased or no
      intraparenchymal flow in nine parotid and in two submandibular glands. CT
      demonstrated parenchymal inhomogeneity with increased and decreased density
      areas, cancers irregular margins, and gland atrophy in 15 parotid and in eight
      submandibular glands. Salivary scintigraphy depicted injuries of the major
      salivary glands detecting their reduced pertechnetate uptake in 12 parotid and in
      eight submandibular glands, with a decreased drug excretion in 12 parotid and in
      12 submandibular glands. DISCUSSION AND CONCLUSION: Our findings confirm that the
      major salivary glands are affected by radiotherapy, which makes their
      morphological and structural monitoring of vital importance. US is the technique
      of choice for its low cost and easy execution, and it is well accepted by the
      patients because it requires no exposure to ionizing radiations. Power Doppler
      provided no relevant information, but it confirmed the high resistance of small
      and middle caliber vessels after radiotherapy. Scintigraphy clearly showed the
      glands involvement demonstrating decreased uptake technetium secretion and
      excretion. In conclusion, US and CT are both extremely useful in the study of the
      morphological changes of the major salivary glands.

PMID- 9638171
TI  - [Use of filgrastim, granulocyte colony stimulating factor (G-CSF), in
      radiotherapy to reduce drop-outs because of radiogenic leukopenia].
AB  - Radiotherapy patients are at risk of developing leukopenia, which risk depends on
      the irradiated volume, the rate of irradiated bone marrow and the radiation dose.
      Radiogenic leukopenia may cause radiotherapy drop-out, with consequent effects,
      on local tumor control and clinical outcome. The introduction of granulocyte
      growth factors, such as filgrastim, has permitted to accelerate normal neutrophil
      count recovery in irradiation-related neutropenia both in vitro and animal
      models; clinical experience in humans is still lacking, relative to both
      indications and scheduling. In the Oncologic Radiotherapy Department of Treviso
      Hospital, 31 patients irradiated for Hodgkin disease, rectal cancer and other
      malignancies, who presented leukopenia requiring treatment discontinuation, were
      given filgrastim to assess its actual effect in avoiding further drop-outs and to
      compare two administration schedules (2 or 3 vials, 30 MIU, weekly). Filgrastim
      treatment was continued throughout the radiotherapy cycles, for 1 to 5 weeks.
      Eighteen patients had received previous chemotherapy and 11 were undergoing
      concurrent 5-fluorouracil chemotherapy-irradiation. A mean 203% increase in
      leukocyte count was observed (136% in the patients treated with 2 vials/week and
      274% in those receiving 3 vials/week); this increase was more apparent in women
      that in men (256% versus 91%) and slightly higher in patients 50 years old and
      with target volumes < 5000 ml. Filgrastin treatment was well tolerated by all
      patients, with no discontinuations due to adverse effects; 9 patients (29%)
      reported skeletal pain, which was marked in 2 of them only. Eighty percent of
      patients completed all the radiotherapy cycles with no discontinuation, while 6
      patients dropped out because leukopenia persisted. Biweekly filgrastim
      administration was effective to prevent unscheduled radiotherapy discontinuation
      in 75% of patients and triweekly administration was effective in 86% of patients.
      In our experience, filgrastim administration was well tolerated and effective in
      decreasing the irradiation drop-outs caused by treatment-related leukopenia.
      Since this drug is rather expensive, we decided to use routinely the lower dosage
      of biweekly administration (with one vial given on Friday and Saturday, to permit
      neutrophil recovery during the day off) and to reserve the higher dosage (3 vials
      a week) to the patients with large body areas, big target volumes and persistent
      leukopenia during previous chemotherapy.

PMID- 9638172
TI  - [Multiple hemangiopericytoma of the left ankle and foot. Magnetic resonance study
      and surgical findings in a case].

PMID- 9638173
TI  - [Necrotizing fasciitis of the neck: report of a case and review of the
      literature].

PMID- 9638174
TI  - [Intracystic papilloma of the male breast associated with monolateral
      gynecomastia. Clinicopathological findings in a case].

PMID- 9638175
TI  - [Hypoplastic left ventricular syndrome: report of a case studied with magnetic
      resonance in the preoperative period].

PMID- 9638176
TI  - [A case of abdominal aortic coarctation studied with angiography and magnetic
      resonance].

PMID- 9638177
TI  - [A case of spontaneous aorto-caval fistula demonstrated with spiral computerized
      tomography].

PMID- 9638178
TI  - [Role of cholangiopancreatography combined with magnetic resonance and
      hepatobiliary scintigraphy with 99mTc-HIDA in the assessment of biliary
      dyskinesia. Report of a case].

PMID- 9638179
TI  - [Retained surgical sponge mimicking bladder neoplasm. Report of a case and
      diagnostic assessment with ultrasonography and computerized tomography].

PMID- 9638180
TI  - [A lung opacity like any other].

PMID- 9638181
TI  - [Scintigraphy of somatostatin receptors in gastropancreatic tumors].

PMID- 9638182
TI  - A perspective on controlling cat populations.

PMID- 9638183
TI  - Bioengineering and food animal veterinarians.

PMID- 9638184
TI  - What is your diagnosis? Nasal lymphoblastic lymphosarcoma causing epistaxis in a
      dog.

PMID- 9638185
TI  - Agents, vehicles, and causal inference in bacterial foodborne disease outbreaks:
      82 reports (1986-1995).
AB  - OBJECTIVE: To examine the study design of, and the practice of causal inference
      in, investigations of bacterial foodborne disease outbreaks occurring in the
      United States and to summarize agents and vehicles identified. DESIGN:
      Retrospective study. PROCEDURE: An online medical reference database was searched
      for reports of bacterial foodborne disease outbreak investigations published
      between 1986 and 1995. Reports were retrieved and reviewed for use of 9 causal
      criteria in investigations. Information on etiologic agents, vehicles,
      seasonality, and primary study design from each outbreak was also retrieved.
      RESULTS: 82 reports were retrieved and reviewed. Coherence, consistency,
      temporality, and strength of association were the causal criteria most commonly
      used in foodborne disease outbreak investigations. Coherence was used in all
      investigations. The number of criteria used ranged from 3 to 7. Meat (n = 20) and
      eggs (12) were the most commonly implicated vehicles. Salmonella sp and
      Escherichia coli O157:H7 accounted for 55% of agents reportedly isolated. Cohort
      and case-control methods were the most common study designs. CLINICAL RELEVANCE:
      Patterns were found in the use of causal criteria in foodborne disease outbreak
      investigations. These criteria can provide veterinarians and other public health
      practitioners with a means to effectively conceptualize, communicate, and
      summarize causal conclusions. The 4 most commonly used criteria may represent
      core criteria that investigators consider most useful in explaining food-borne
      disease outbreaks.

PMID- 9638186
TI  - Effect of intracameral administration of carbachol on the postoperative increase
      in intraocular pressure in dogs undergoing cataract extraction.
AB  - OBJECTIVE: To determine whether intracameral injection of carbachol at the
      completion of phacoemulsification in dogs would prevent the increase in
      intraocular pressure (i.o.p) that can develop during the first 24 hours after
      surgery. DESIGN: Randomized controlled trial. ANIMALS: 32 adult dogs undergoing
      elective unilateral or bilateral phacoemulsification. PROCEDURE: Dogs were
      randomly assigned to 1 of 4 groups with 8 dogs/group: phacoemulsification and
      intracameral administration of 0.5 ml of 0.01% carbachol at the end of surgery;
      phacoemulsification, intraocular lens implantation, and intracameral
      administration of 0.5 ml of 0.01% carbachol; phacoemulsification and intracameral
      administration of 0.5 ml of balanced salt solution; and phacoemulsification,
      intraocular lens implantation, and intracameral administration of 0.5 ml of
      balanced salt solution. Intraocular pressure was measured at 3 and 6 hours and
      the morning after surgery. Aqueous flare was also measured 6 hours and the
      morning after surgery. RESULTS: None of the dogs treated with carbachol developed
      postoperative ocular hypertension (i.e., IOP > 27 mm of Hg), whereas 12 of 16
      control dogs had ocular hypertension 3 hours after surgery. Intraocular pressure
      3 hours after surgery was not significantly associated with phacoemulsification
      time or phacoemulsification power or with whether the dog received an intraocular
      lens implant. Severity of aqueous flare was similar for treated and control dogs.
      CLINICAL IMPLICATIONS: Results suggested that intracameral administration of
      0.01% carbachol at the end of surgery was a safe and efficacious method of
      preventing the postoperative increase in IOP associated with phacoemulsification
      in dogs.

PMID- 9638187
TI  - Association between hyperadrenocorticism and development of calcium-containing
      uroliths in dogs with urolithiasis.
AB  - OBJECTIVE: To determine, among dogs with urolithiasis, whether dogs that had
      hyperadrenocorticism would be more likely to have calcium-containing uroliths
      than would dogs that did not have clinical evidence of hyperadrenocorticism.
      DESIGN: Retrospective case-control study. ANIMALS: 20 dogs that had urolithiasis
      and hyperadrenocorticism and 42 breed-matched dogs that had urolithiasis but did
      not have clinical evidence of hyper-adrenocorticism. PROCEDURE: Signalment,
      urolith composition, results of bacterial culture of urine, and results of
      adrenal axis tests were recorded. A multivariate logistic regression model was
      created, including terms for age, sex, and hyperadrenocorticism. The outcome
      variable was presence or absence of calcium-containing uroliths. RESULTS: Among
      dogs with urolithiasis, those that had hyperadrenocorticism were 10 times as
      likely to have calcium-containing uroliths as were dogs that did not have
      clinical evidence of hyperadrenocorticism (odds ratio, 10.5; 95% confidence
      interval, 1.5 to 23.4). Neutered and sexually intact females were less likely to
      have calcium-containing uroliths than were neutered males (odds ratios, 0.041
      [95% confidence interval, 0.0057 to 0.29] and 0.024 [95% confidence interval,
      0.0012 to 0.51, respectively). CLINICAL IMPLICATIONS: Prompt diagnosis and
      treatment of hyperadrenocorticism may decrease prevalence of calcium-containing
      uroliths in dogs.

PMID- 9638188
TI  - Apparent primary ossification of the menisci in a dog.
AB  - A 2-year-old Collie was examined after it developed acute lameness in the right
      hind limb. Palpation of the right stifle elicited signs of pain, but a cranial
      drawer sign could not be elicited during palpation of the joint. Radiography
      revealed mineralized opacities in the craniolateral and caudal portions of the
      right stifle joint. Exploratory arthrotomy of the right stifle joint revealed a
      firm mass in the cranial horn of the lateral meniscus, which was characterized as
      osseous metaplasia in the cranial and caudal menisceal horns on histologic
      examination. Other abnormalities were not identified during surgery. Results of
      histologic examination, radiologic evidence, and observations during exploratory
      surgery supported a diagnosis of primary lateral meniscal ossification of the
      right stifle joint. Radiographs were obtained of the contralateral stifle joint
      when the dog was clinically normal (5 weeks after arthrotomy), and mineralized
      opacities were found in the lateral meniscus of this limb as well. Clinical signs
      may not be associated with primary intrameniscal ossification initially; type and
      location of ossification may affect likelihood and severity of clinical signs and
      secondary joint damage. Initial treatment for menisceal ossification is
      conservative (anti-inflammatory medications) unless there is a concurrent
      pathologic process that requires surgical repair.

PMID- 9638189
TI  - Hepatocellular toxicosis associated with administration of carprofen in 21 dogs.
AB  - A diagnosis of hepatocellular toxicosis attributable to carprofen administration
      was made in 21 dogs on the basis of development of clinical signs and
      clinicopathologic abnormalities associated with hepatic disease and
      histopathologic documentation of hepatic necrosis. Clinical signs of toxicosis
      were anorexia, vomiting, and icterus. Hyperbilirubinemia and high serum
      activities of alanine transaminase, alkaline phosphatase, and aspartate
      transaminase were the most notable clinicopathologic abnormalities. In 7 of 9
      dogs in which urinalyses were performed, abnormalities suggestive of renal
      tubular disease were detected. Clinical course of toxicosis was variable;
      however, most dogs had resolution of clinical signs and improvement or resolution
      of biochemical abnormalities with discontinuation of the drug and administration
      of supportive care. As with any medication, clients should be informed of
      possible adverse effects and reactions associated with administration of
      carprofen. In the event of those signs, clients should be instructed to
      immediately discontinue administration of carprofen to their dog and contact
      their veterinarian.

PMID- 9638190
TI  - Prognostic factors for dogs with granulomatous meningoencephalomyelitis: 42 cases
      (1982-1996).
AB  - OBJECTIVE: To assess signalment, clinical signs, results of CSF analysis,
      treatment, and survival times in dogs with granulomatous meningoencephalomyelitis
      (GME) and to identify factors associated with survival. DESIGN: Retrospective
      study. SAMPLE POPULATION: Medical records of 42 dogs with GME. PROCEDURE:
      Information on signalment, neurolocalization, presence of focal or multifocal
      signs, results of CSF analysis, method of treatment, and time from onset of
      clinical signs to death was retrieved from medical records of each dog. Kaplan
      Meier survival analysis was used to assess survival times. The Cox proportional
      hazards method was used to identify predictors of survival. RESULTS: Females and
      toy and terrier breeds were predisposed to GME. Half of the dogs had focal
      neurologic signs, and half had multifocal involvement. Clinical signs referable
      to the forebrain were most common with focal involvement, whereas signs referable
      to the forebrain and brainstem were most commonly seen with multifocal
      involvement. Cerebrospinal fluid analysis commonly revealed a mononuclear
      pleocytosis. Survival times ranged from 1 to > 1,215 days. Significant
      differences in survival times were demonstrated for the following factors: focal
      versus multifocal clinical signs, neurolocalization of focal signs, and treatment
      with radiation. Radiation was the only independent predictor of survival.
      CLINICAL IMPLICATIONS: Dogs with signs suggesting focal involvement of GME tend
      to survive longer than those with multifocal involvement. Radiation is an
      effective treatment for dogs with GME, particularly those with clinical signs
      suggesting focal involvement.

PMID- 9638191
TI  - Results of double-contrast cystography in cats with idiopathic cystitis: 45 cases
      (1993-1995).
AB  - OBJECTIVE: To determine results of double-contrast cystography in cats with
      idiopathic cystitis. DESIGN: Retrospective study. ANIMALS: 45 cats with clinical
      signs of nonobstructive lower urinary tract disease for which an underlying cause
      could not be determined. PROCEDURE: Medical records and double-contrast
      cystograms performed initially and during 6- and 12-month reevaluations were
      reviewed. RESULTS: 105 cystograms were reviewed. Fifteen (33%) cats had
      abnormalities evident on cystograms obtained at the time of initial examination.
      Of these, only 1 had abnormalities 6 and 12 months later. Thirty cats did not
      have abnormalities evident on cystograms obtained at the time of initial
      examination. Of these, 1 had abnormalities on a cystogram performed 6 months
      later and another had abnormalities on a cystogram performed 12 months later.
      Abnormalities evident on cystograms included focal thickening of the bladder wall
      (n = 11), diffuse thickening of the bladder wall (6), irregularities of the
      bladder mucosa (10), decreased opacity of the bladder wall (3), increased opacity
      of the bladder mucosa (3), filling defects (4), contrast medium in unexpected
      locations (3), and altered ureteral opacity (15). CLINICAL IMPLICATIONS: Results
      suggested that a large percentage of cats with idiopathic cystitis do not have
      cystographic abnormalities when initially examined but that abnormalities may be
      apparent during follow-up evaluations. In addition, a smaller percentage of cats
      with idiopathic cystitis may have nonspecific cystographic signs of cystitis or
      hemorrhage. Leakage of contrast medium into the peritoneal space during
      cystography does not necessarily require surgical management.

PMID- 9638192
TI  - Development and duration of antibody response against Ehrlichia equi in horses.
AB  - OBJECTIVE: To characterize antibody response in horses with clinical signs of
      Ehrlichia equi infection. DESIGN: Prospective study. ANIMALS: 13 horses with
      confirmed acute E equi infection. PROCEDURE: Sequential serum sampling was
      performed in Connecticut and New York during 1995 and 1996 to identify horses
      with naturally acquired equine granulocytic ehrlichiosis (EGE). Horses with
      clinical signs of EGE (i.e., fever without respiratory involvement) were
      confirmed as having E equi infection by polymerase chain reaction detection of
      ehrlichial DNA and by a minimum fourfold increase in total antibody titer by
      indirect fluorescent antibody staining methods. Infection was corroborated by use
      of DNA sequencing. RESULTS: 11 of 13 horses did not have detectable antibody in
      serum samples obtained at onset of disease. Seroconversion was evident in samples
      obtained 19 to 81 days thereafter. Median time to peak antibody response was 46
      days after onset and median titer was 1:320. For 11 of 13 horses, antibody titers
      were < or = 1:40 by 215 days after onset. CLINICAL IMPLICATIONS: E equi was found
      in horses in the northeastern United States and caused EGE. Concentration of
      antibodies to E equi increased within 19 to 81 days of disease onset and were low
      during early weeks of infection. Therefore, antibody detection may be of limited
      value for early serologic diagnosis. We suggest that disease may develop from a
      reinfection, and retrospective serologic studies to determine exposure to E equi
      may reflect a disproportionate number of negative reactions.

PMID- 9638193
TI  - Primary hyperparathyroidism caused by a functional parathyroid adenoma in a
      horse.
AB  - A 14-year-old Arabian gelding had weight loss and anorexia of 3 weeks' duration.
      Results of repeated laboratory tests revealed persistent hypercalcemia and serum
      phosphorus concentration that was within or less than the reference range.
      Parathyroid hormone concentration was high. Histologic examination of specimens
      obtained at necropsy revealed parathyroid adenoma. A diagnosis of primary
      hyperparathyroidism attributable to a functional parathyroid adenoma was made.
      Abnormalities in calcium and phosphorus concentrations were similar to those seen
      with primary hyperparathyroidism in dogs, in which this syndrome is best
      described. Primary hyperparathyroidism should be considered to be a potential
      cause of hypercalcemia in horses in which other more common causes of
      hypercalcemia, such as humoral hypercalcemia of malignancy, nutritional secondary
      hyperparathyroidism, chronic renal failure, vitamin D toxicosis, and bony or
      granulomatous disease, are ruled out.

PMID- 9638194
TI  - Effects of tilmicosin on acute undifferentiated respiratory tract disease in
      newly arrived feedlot cattle.
AB  - OBJECTIVES: To evaluate effects of tilmicosin when used in fever-based and
      metaphylactic treatment programs to attenuate acute undifferentiated bovine
      respiratory disease (BRD) in cattle that recently arrived at feedlots, and to
      evaluate the effects of tilmicosin for the treatment of BRD. DESIGN: Randomized
      block controlled study. ANIMALS: 1,639 calves from livestock auctions.
      PROCEDURES: Cattle were assigned to 3 groups. Cattle in the nonmedicated
      (control) group were not given antibiotics during processing. Cattle in the fever
      based treatment group were given tilmicosin (10 mg/kg [4.5 mg/lb] of body weight,
      s.c.) during processing when their rectal temperature was > or = 40 C (104 F).
      All cattle in the metaphylactic treatment group were given tilmicosin (10 mg/kg,
      s.c.) during processing. Calves with BRD were treated with tilmicosin (10 mg/kg,
      s.c.). RESULTS: Morbidity rates in the metaphylactic (30.4%) and fever-based
      (44.7%) treatment groups were less than that for the nonmedicated group (54.8%).
      Mortality rate for the metaphylactic group during the first 28 days (1.1%) and
      during the entire study (1.7%) was less than that for the nonmedicated group (3.3
      and 4.6%, respectively). Differences were not observed in therapeutic response
      rates among calves with BRD that were treated. CLINICAL IMPLICATIONS: Fever-based
      and metaphylactic treatment programs that used tilmicosin decreased the
      prevalence of BRD and improved growth of calves. Metaphylactic treatment
      decreased the number of fatalities caused by BRD in high-risk calves. Fever-based
      treatment was less effective than metaphylactic treatment for decreasing the
      prevalence of BRD in newly arrived cattle.

PMID- 9638195
TI  - Isolation of Salmonella serotypes from feces of pigs raised in a multiple-site
      production system.
AB  - OBJECTIVE: To determine the prevalence and serotypes of Salmonella organisms in
      feces of pigs raised in a modern, multiple-site production system. DESIGN: Cross
      sectional study of prevalence. SAMPLE POPULATION: Swine housed on 7 farms (1 gilt
      development farm, 2 breeding farms, 1 nursery farm, and 3 finishing farms) that
      formed a multiplesite production system. PROCEDURE: Fecal samples were obtained
      from 792 pigs (96 to 202/farm) and submitted for bacteriolgic culture of
      Salmonella organisms. RESULTS: Salmonellae were isolated from pigs on all 7 farms
      and from 95 of 792 (12%) fecal samples. Prevalence ranged from 3.4% at the gilt
      development farm to 18 and 22% at the breeding farms. Serotypes identified were
      Salmonella derby, S typhimurium var. copenhagen, S heidelberg, S typhimurium, S
      mbandaka, S worthington, and S tennessee. No single serotype was not isolated
      from all the farms of the production system and the most prevalent serotypes at
      the 3 finishing farms (S typhimurium or S typhimurium var. copenhagen) were not
      isolated from the breeding or nursery farms. CLINICAL IMPLICATIONS: Upstream
      infection (pigs infected before arriving at finishing farms) appears to be an
      unimportant source of Salmonella infection of finished hogs in multiple-site
      systems. High prevalence of Salmonella shedding in breeding animals suggests that
      food products derived from culled breeding livestock may be an important source
      of foodborne disease.

PMID- 9638196
TI  - [Characteristics of ischemic heart disease patients with late ventricular
      potentials].
AB  - The purpose of this study was to compare ischemic heart disease (IHD) patients
      with and without late potentials (LP) by using noninvasive diagnostic methods as:
      echocardiographic examination, exercise testing, 24-hours Holter ambulatory
      monitoring, recording of atrial and ventricular signal-averaged ECG. Examination
      covered 25 IHD pts (12 male and 13 female) with LP, mean age 58.6 +/- 7.3 (group
      I) and 100 IHD pts (65 male and 35 female) without LP, mean age 56.8 +/- 8.5
      (group II). Summing up, it should be stated that despite showing tendencies to
      much often occurrences of ventricular arrhythmias on Holter monitoring and silent
      ischemia during exercise testing in IHD pts with LP we were unable to indicate
      distinctive differentiating parameters between investigated groups.

PMID- 9638197
TI  - [Evaluation of treatment effectiveness for Helicobacter pylori infections in
      children].
AB  - An assessment was performed of the effectiveness of treatment of Helicobacter
      pylori infection and coexisting diseases in children with two and three drugs. A
      high percent of bacterial eradication and cure of the coexistent conditions were
      achieved particularly in the group of children treated with three drugs.

PMID- 9638198
TI  - [Study of nitroblue tetrazolium reduction by granulocytes in workers handling x
      ray equipment].
AB  - In 44 persons (25 women and 15 men), workers handling X-ray equipment in X-ray
      laboratories the ability was studied of nitroblue tetrazolium (NBT) reduction by
      neutrophils. The obtained results were compared with a control group. Besides
      that subgroups were isolated taking into account the sex of the studied subjects
      and duration of their work with X-ray equipment (over five years and below five
      years). In the workers handling X-ray equipment and in the isolated subgroups of
      women and men, the index of spontaneous NBT reduction turned out to be
      statistically significantly higher than that in the control group. In the group
      of studied workers the index of latex-stimulated NBT reduction was statistically
      significantly lower than that in the control group. Taking into account the
      duration of work with X-ray equipment in the subgroups of women and men working
      for over five years, the lowest index of phagocytes was noted. On the basis of
      the obtained results the following conclusions were formulated: 1. In workers
      handling X-ray equipment disturbances occur of peripheral blood neutrophil
      metabolism assessed in the NBT test. 2. Neutrophil phagocytic activity is
      weakened in persons working over five years with X-ray equipment.

PMID- 9638199
TI  - [Usefulness of transcutaneous oximetry in vascular surgery].
AB  - The assessment is presented of the value of transcutaneous oximetry in vascular
      surgery and in choosing the level of ischaemic limb amputation. Transcutaneous
      measurements of oxygen pressure (tcp02) were performed in 172 patients operated
      on for chronic ischaemia of the lower limbs before and three weeks after the
      operation. The studied subjects had the following operations done: bifurcated or
      unilateral aortofemoral bypass, femoropopliteal bypass, restoration of patency of
      the iliac and femoral arteries, lumbar sympathectomy, lower limb amputation. The
      studies were carried out using Hellige SM 361 oxymonitor and a similar Polish
      device. For oximetric measurements superficial skin sensor (Clark's polarographic
      electrode) was used, which was applied into the dorsum of the foot and medial
      crural surface. Transcutaneous oximetry seems to be a useful method for the
      assessment of the results of operations restoring blood flow in lower limb
      arteries. It makes possible to evaluate the results of lumbar sympathectomy.
      Transcutaneous measurements of oxygen pressure are also a useful method for the
      assessment of results of amputation of chronically ischaemic lower limb.

PMID- 9638200
TI  - [Evaluation of fear and analysis of personality structure of women at risk for
      premature and after term labor].
AB  - Psychological studies were performed in 57 pregnant women at risk for premature
      labour and 36 at risk for after term labour. The level of fear was evaluated
      using the Spielberger STAI questionnaire. The structure of fear and restlessness
      was studied using the R.B. Cattell's five factor Self-estimation Sheet. The
      analysis of personality structure was performed on the basis of results of the
      MMPI-WISKAD test. In the patients in both studied groups, groups an increased
      level of situational and persistent fear was found. Women at risk for premature
      labour are characterized by higher level of fear of neurotic character resulting
      from disharmonious personality. In women delivered after term the fear is of
      reactive character. Women at risk for after term labour are characterized by a
      higher degree of personality integration and more effective ability to control
      fear. Women at risk for premature labour are characterized by disharmonious
      personality and simultaneously they use more primitive protective mechanisms.
      Women delivered after term are characterized by higher degree of personality
      integration and more effective ability to control fear.

PMID- 9638201
TI  - [Evaluation of some hemodynamic indices in 15 to 18 year old boys with lipid risk
      factors for atherosclerosis].
AB  - The aim of the work was an attempt at answering the question whether there is any
      correlation between the haemodynamic indices describing arterial elasticity
      assessed by physical analysis of the circulatory system and lipid risk factors
      for arterial atherosclerosis in boys aged 15 to 18 years. The studies included 45
      boys with lipid risk factors for atherosclerosis. The control group included 53
      boys without lipid risk factors. In boys aged 17-18 years with lipid risk factors
      for atherosclerosis as compared with their peers with normal serum lipid level, a
      statistically significant change of arterial elasticity was found. A positive
      correlation was also found between the increased serum cholesterol level and the
      values of air-chamber elasticity index and peripheral vascular resistance, and a
      negative correlation was demonstrated between the decreased serum HDL-cholesterol
      concentration and the increase of pulse wave velocity in the aorta, air-chamber
      elasticity index and peripheral vascular resistance.

PMID- 9638202
TI  - [Profiles of daily secretion of ACTH, beta-endorphins and cortisol in patients
      after minor craniocerebral trauma].
AB  - In 12 men aged 20-25 men who had minor craniocerebral trauma the profiles of
      daily secretion of ACTH, beta-endorphin and cortisol were studied. The studies
      were carried out on the second day after the trauma. Plasma concentrations of the
      hormones were determined on 8.00, 12.00, 17.00 and 22.00 hours. Statistically
      significantly increased, in relation to healthy persons, (p < 0.01) values of
      plasma hormone concentration were found at all time points. In 50% of the
      patients (six cases) a disturbance was found of the profile of daily secretion of
      ACTH and beta-endorphin. The disturbance of the profile of cortisol secretion was
      found only in one patient.

PMID- 9638204
TI  - [Carcinoid--advances in diagnosis and treatment].
AB  - Carcinoid is one of the most frequently diagnosed neuroendocrine tumours. It
      develops slowly but grows by infiltration and has the ability to give metastases
      in distant organs. The clinical picture is very diverse and in 10% of cases the
      signs called carcinoid syndrome develop. Not infrequently it produces also
      peptide hormones. In the present paper the most modern diagnostic methods,
      possibilities of surgical and pharmacological treatment of this extremely
      interesting neoplasm are discussed.

PMID- 9638203
TI  - [Iatrogenic esophageal perforation].
AB  - A total of 213 patients with a foreign body in the oesophagus was treated in our
      unit between 1980-1990. Most of the foreign bodies were impacted in the cervical
      oesophagus. Oesophagoscopy were carried out under general anaesthesia in all
      cases. iatrogenic perforation of oesophagus was encountered in ten cases. Our
      results suggest that most instrumental perforation of the esophagus should be
      managed surgically. Drainage and closure of cervical perforations yields good
      results. Nonoperative management night be entertained in minimally symptomatic
      patients harboring a late, locally contained perforation without signs of ongoing
      sepsis.

PMID- 9638205
TI  - [Differential diagnosis of enlarged scrotum].

PMID- 9638206
TI  - [Spa treatment of urogenital system diseases].
AB  - Attention was paid to the underestimated value of spa treatment of urinary system
      diseases. The methods of this type of therapy, and indications and
      contraindications in the treatment of urological diseases are discussed. Such
      therapy accelerates recovery, has prophylactic values and reduces the cost of
      treatment.

PMID- 9638207
TI  - [Coexistence of Pneumocystis carinii infection with pertussis].

PMID- 9638208
TI  - [Use of salazopyrin in Schonlein-Henoch disease].
AB  - A favourable effect was achieved of treatment with salazopyrin of severe
      abdominal of Schoenlein-Henoch disease (SH). Salazopyrin was used in two children
      with generalized form of SH, with paroxysmal abdominal pain and bleeding from the
      gastrointestinal tract.

PMID- 9638209
TI  - [Iatrogenic uretero-vaginal fistula].
AB  - A case is presented of iatrogenic late ureterovaginal fistula treated with
      ureteral transplantation with a very good result. It was found that this was the
      method of choice in this type of fistulae, and temporary internal ureteral
      splinting was worthwhile to use as a prophylaxis of iatrogenic ureteral damage.

PMID- 9638210
TI  - [Evaluation of ciliary epithelium cilia in diagnosis of Kartagener syndrome].
AB  - A case of 41 year man with Kartagener's syndrome presenting incomplete clinical
      symptoms of disease was described. Diagnosis was established by electron
      microscopy analysis of nasal mucous membrane cilia biopsy. Ultrastructurally the
      complete lack of dynein arms was found.

PMID- 9638211
TI  - [Foreign body in the frontal sinus].
AB  - The authors describe the case of the foreign body in frontal sinus left there
      after prior surgery. The case was treated surgically with good results.

PMID- 9638212
TI  - [Bioethical aspects of ecology and medicine in an industrialized society].

PMID- 9638213
TI  - [II. Physicians and their practice].

PMID- 9638214
TI  - [Activity of beta-hexosaminidase in serum of patients with alcoholic and
      nonalcoholic liver diseases].
AB  - The total activity and thermostable activity of serum beta-hexosaminidase were
      determined in alcohol-dependent patients with liver damage, in non-drinking
      hepatic patients, in alcohol-dependent presently drinking patients who had no
      hepatic symptoms and signs, and in healthy persons drinking alcohol occasionally
      in moderate quantities who served as the control group. The enzyme activity was
      determined by the spectrofluorometric method using 4-methylumbelliferone
      derivative as substrate. The activity of beta-hexosaminidase in both groups with
      liver disease of both alcoholic and non-alcoholic origin exceeded significantly
      the control values. In those alcohol-dependent patients with liver disease who
      did not stop drinking, the activity was higher after recent drinking in relation
      to that after a period of abstinence. The determination can thus serve as a
      marker of alcohol abuse also in alcohol-dependent patients with liver damage. The
      share of thermostable component in the total increase of beta-hexosaminidase
      activity in alcohol-abusing persons was higher than that in the case of hepatic
      diseases of non-alcoholic origin.

PMID- 9638215
TI  - [Duphalac (lactulose) in the treatment of chronic constipation in children].
AB  - The aim of this study was to estimate the effectiveness of DUPHALAC preparation,
      produced by Solvay-Pharma, in treatment of functional chronic constipation. 112
      children, aged 10 months-15.5 years were examined. DUPHALAC appeared to be very
      effective, were examined. Only two patients did not accept its taste. Rapidly
      (approximately after 2.5 weeks) improvement was achieved such as of restoration
      normal peristalsis and of previously disturbed defecation rhythm, softening of a
      stool, regression of pain and/or dyspeptic ailments, encopresis and improvement
      of appetite. In no case undesirable side effects were observed.

PMID- 9638216
TI  - [The value of anti-inflammatory effectiveness of Apranax 550 and Voltaren 50
      after knee joint arthroscopic surgery].
AB  - The results are presented of the study of the effectiveness of non-steroid anti
      inflammatory drugs (Apranax, Voltaren) on the basis of observation of 60 patients
      in a double blind trial after knee joint arthroscopic operations. The
      administration of Apranax 550 or Voltaren 50 within the period of 10 days after
      the operation decreased significantly the incidence of inflammatory reactions.
      Apranax 550 was acting more rapidly and more effectively in elimination of
      clinical signs and symptoms of inflammation, and the patients were not reporting
      any adverse effects.

PMID- 9638217
TI  - [Evaluation of treatment results for lateral ankle fractures].
AB  - An analysis was performed of 18 lateral ankle fractures with fracture fissure
      running from above-back forward and down-ward. In this group, 15 cases were
      treated conservatively and three cases surgically. In eight patients an evident
      limitation of pronation movements was found, the remaining movement being limited
      to a lesser degree. In six patients traces after previous separation of
      tibiofibular syndesmosis were found. The conservative treatment failed to
      maintain normal conditions in the talocrural joint.

PMID- 9638218
TI  - [Conservative treatment of calcaneal fractures].
AB  - The results of conservative treatment has been presented in 19 patients treated
      for calcaneal bone fracture. The most common changes are: 1--dislocation of
      loading point; 2--disorder of foot statics; 3--degenerative and deformity causing
      changes; 4--reduction of walking efficiency which made some patients change their
      profession; 5--quite frequent recommendation to subtalar arthrodesis.

PMID- 9638219
TI  - [Anxiety-depressive neurosis in ambulatory treatment conditions].
AB  - A group of 48 patient was treated for fear and depressive neurosis at Psychical
      Health Consulting Unit. They were observed and evaluated in period from April
      5th, 1990 till December 31st, 1990. The group included 32 women and 16 men. The
      conclusion is the women was 66.6% and the men 33.4%. 23 persons (47.9%) was
      treated with Doxepin and 25 persons (52.1%) was treated with Alprazolam (Xanax,
      Valeans). The administration of one medicine was the rule, in case of the failure
      a medicine was change for another one. One used also individual psychotherapy.

PMID- 9638220
TI  - [Endocrine ophthalmopathy--etiopathology].
AB  - Endocrine ophthalmopathy is regarded as organ specific disease of
      autoimmunological origin. It occurs most frequently in patients with Graves
      disease, less frequently in those with Hashimoto thyroiditis. The presence of HLA
      DR-3 and HLA b-8 antigens, cigarette smoking, treatment with radioiodine, and
      thyroid function disturbances predispose for the development of the disease. On
      the other hand, the most important pathogenetic mechanism is fibroblast
      stimulation and increased collagen and glucosaminoglycans production within the
      extrabulbar muscle interstitium.

PMID- 9638221
TI  - [Diabetic osteopathy].

PMID- 9638222
TI  - [Ototoxicity of drugs].
AB  - The paper included the most current information about the mechanisms of
      ototoxicity of five groups of the most popular drugs: a) antibiotics, b)
      chemotherapeutics (cytostatic) agents, c) loop diuretics, d) salicylate and
      nonsteroidal anti-inflammatory drugs, as well as e) progestagen contraceptives
      minimized or even prevented by thoughtful selection of drug, attention to risk
      factors and careful patient monitoring.

PMID- 9638223
TI  - [Interstitial cystitis--diagnosis and etiopathogenesis].

PMID- 9638224
TI  - [Alcoholic withdrawal delirium].
AB  - The actual progress of medical studies, reach to 1% in comparison with former
      data 20% a number of death in delirium tremens. The aim of this study is the
      presentation the symptoms of alcohol psychosis, as well as of various methods of
      it's cure. To choose of right therapy is sometimes very difficult for the
      physician. In this work one tries to explain pathogenesis of delirium tremens.
      Author's doctors of first contact in achieving right diagnosis and therapy.

PMID- 9638225
TI  - [Scar changes in the bronchus caused by a foreign body].
AB  - Long lasting recurrent pneumonia in 13-year-old girl was been described. The main
      cause was the foreign body (pawn of plastic) covered in intermediate bronchus.
      Bronchoscopy revealed scars in type of "bridges" narrowing intermediate bronchus.
      The foreign body and the scar changes were removed.

PMID- 9638226
TI  - [Lesniowski-Crohn disease in the esophagus].
AB  - In the paper two cases are presented of Lesniowski-Crohn disease located in the
      oesophagus. The clinical course, diagnosis and surgical treatment are described.
      The attention is paid to the difficulties in differentiation of lesions
      developing in the course of this disease from malignancy, exerting significant
      influence on the choice of surgical management.

PMID- 9638227
TI  - [High esophageal perforation in a 2.5 year old child].
AB  - A case is presented of a 2,5-year-old child in whom high oesophageal perforation
      developed after gastric lavage due to ingestion of lethal dose of salicylates.
      Strong, locally irritating action of salicylates on the oesophageal mucosa was
      demonstrated which, most probably, was the cause of the perforation.

PMID- 9638228
TI  - [Foreign bodies in the bile ducts as a cause of jaundice].

PMID- 9638229
TI  - [The development of hydrocephalus after intracranial hemorrhage in an infant with
      meningoencephalitis].
AB  - The present paper describes the case of hydrocephalic infant resulting from the
      intracranial haemorrhage with coexisting meningitis. The evolution of brain
      changes in sonography is shown.

PMID- 9638231
TI  - [A case of primary pulmonary hypertension in a 52-year old man].
AB  - The presented case of primary pulmonary hypertension is worth attention in view
      of rare incidence in men, especially those over 50 years of age. It was possible
      to observe the course of the disease and to perform examinations confirming the
      diagnosis. The unavoidable and rapid progression of lesions, extremely poor
      prognosis and lack of possibilities of causal treatment should be stressed.

PMID- 9638230
TI  - [A case of Lyell's syndrome caused by carbamazepine].
AB  - A case is described of Lyell syndrome in a female patient with schizoaffective
      psychosis which developed several days after addition of carbamazepine to the
      psychotropic treatment used. After withdrawal of the drug and three weeks of
      treatment with prednisone in dose 60 mg daily, antibiotic therapy and intensive
      dermatological-nursing care, full remission of skin lesions and oral mucosa
      lesions was obtained.

PMID- 9638232
TI  - [Hepatitis virus infection as a possible cause of cholangiopathy].

PMID- 9638233
TI  - [I. Physicians and their practice].

PMID- 9638234
TI  - [Historical outline of electrocardiography].

PMID- 9638235
TI  - [Clinical picture of acute myocardial infarction depending on the use of
      pharmacologic treatment schemes].
AB  - The aim of the work was a retrospective comparison of the clinical course of
      acute myocardial infarction depending on the applied schema of pharmacological
      treatment: streptokinase, heparin, antiplatelet drugs. The analysis included 409
      patients (261 men and 148 women aged 31-85 years; mean age 61 years). Twelve-lead
      ECG records were analysed: 24 hours, 48 hours, 72 hours, 7 days and 14 days after
      the onset of the disease. The sum of ST segment elevations, sum of Q wave
      amplitude and the sum of R wave amplitude in the leads showing signs of
      infarction were taken into account. The mean was calculated from the highest
      values of AspAT and AlAT. The haemodynamic, arrhythmic and other early and late
      complications occurring during the treatment were subjected to analysis; the per
      cent index of deaths in each group was also calculated. In the patients treated
      with streptokinase, in comparison to the patients treated with heparin and
      antiplatelet drugs, earliest stabilization was observed of the ECG pattern in the
      form of: reduction of ST segment elevation, reduction of R wave height, and
      formation of a stable Q wave. AspAT and AlAT values were highest in the group of
      patients treated with streptokinase in relation to the remaining groups of
      patients. Arrhythmic and haemodynamic complications occurred less frequently in
      the patients treated with streptokinase and heparin than in those treated with
      antiplatelet drugs. On the other hand, late and other early complications were
      observed less frequently in the patients treated with antiplatelet drugs. The
      mortality during hospitalization period was similar in individual groups of
      patients, being 7.2% for the patients treated with streptokinase, 7.5% for those
      treated with antiplatelet drugs, and 9% for those treated with heparin.

PMID- 9638236
TI  - [The influence of patient age on the effectiveness of bronchodilators].
AB  - The beta adrenergic receptors are exposed to variety of factors modulating their
      activity. We analyzed the sensitivity to Salbutamol in asthmatic patients divided
      into three group (I-30 yr; II-30-50 yr; III-50 yr). The effectiveness of beta
      adrenergic receptors was assessed by means of estimation of plasma cAMP level
      before and after Salbutamol infusion. We didn't found any significant differences
      in plasma cAMP changes between investigated group of patients.

PMID- 9638237
TI  - [The effect of multiple plasmapheresis on levels of apolipoprotein B, fibrinogen
      and cholesterol in blood donors].

PMID- 9638238
TI  - [Evaluation of arrhythmia incidence during gastroscopy examination].

PMID- 9638239
TI  - [Investigations in the use of mogramostime (GM-CSF) in patients with acute
      leukemia].

PMID- 9638240
TI  - [Treatment of advanced pancreatic cancer with interferon alpha, tumor necrosis
      factor and 5-fluorouracil (preliminary report].
AB  - This paper presents the first outcomes of a combined therapy of advanced cancer
      of pancreas with Interferon alpha, Tumor Necrosis and 5-Fluorouracil. Every
      subject underwent surgical treatment, but only in two cases partial resection was
      done. In the other subject only palliative operations were performed because of
      advances stages of neoplastic process. All patients were followed up during the
      time ranged between from 2.5-13.5 months. Complete remission was observed in one
      patient (survival time--9 months). In three subjects partial remission was
      reported, whereas in the left part of our cohort the general condition was
      steady. This research would be continued.

PMID- 9638241
TI  - [Long term treatment results for chloride diarrhea].

PMID- 9638242
TI  - [Evaluation of selected enzyme activity in neutrophils and in blood serum of x
      ray technicians].

PMID- 9638243
TI  - [Vaginal candidiasis in parturients].

PMID- 9638244
TI  - [Biotherapy in hematology. Biology and clinical use of granulocyte colony
      stimulating factor (G-CSF)].
AB  - G-CSF is one of drugs which play important role as one of link of the long chain
      used in biotherapy of cancers. However effect of G-CSF was known more than 20
      years ago, it doesn't exclude chemotherapy and/or radiotherapy but it is
      effective complementary of this methods. The purpose of this short review is to
      describe biological activity, effects and clinical applications of G-CSF.

PMID- 9638245
TI  - [The role of the thymus in the human body].
AB  - The work deals with contemporary opinions on the endocrinological function of
      thymus. The latest information concerning T cell maturation has also been
      provided. It has been shown that there is a direct relationship between the
      process of lymphocyte T proliferation and formation of the organism tolerance to
      self. The current opinions dealing with the phenomenon of the thymus involution
      have been given stressing its advantageous significance for human organism. The
      work shows wide connections of the gland in question with other organs. The
      participation of thymus in pathogenesis of some disease entities has also been
      presented.

PMID- 9638246
TI  - [Stimulation of fetal lung development].

PMID- 9638247
TI  - [Pathophysiology of cerebral ischemia].

PMID- 9638248
TI  - [Central nervous system infections in patients with AIDS].
AB  - Central Nervous System (CNS) is very common site of the opportunistic infections
      in patients with AIDS. Patients, who died because of AIDS have described
      pathology of CNS in 80% in autopsy series. Toxoplasmic encephalitis (TE) is the
      most common infection in the course of AIDS, and it touches 25-50% of the HIV
      infected people. The treatment of TE is very difficult, but relapses are very
      often and primary and secondary prophylaxis of TE is necessary. Fungal infections
      (particularly cryptococcal meningitis) are very unpopular in immunocompetent
      patients; in HIV-infected people Cryptococcus neoformans is the cause of the 30%
      of encephalitis. Viral and bacterial encephalitis, they are not very common in
      AIDS patients.

PMID- 9638249
TI  - [Losartan, new angiotensin receptor antagonist--a challenge for enzyme converting
      angiotensin inhibitors?].

PMID- 9638250
TI  - [Malignant neoplasms of the small intestine as a cause of obstruction].

PMID- 9638251
TI  - [Giant ovarian cyst in a 15-year girl].

PMID- 9638252
TI  - [Endometriosis with colonic involvement].

PMID- 9638253
TI  - [Vestibular neuritis in the course of a tick-borne viral meningitis infection].

PMID- 9638254
TI  - [A case of leptospirosis with respiratory tract symptoms].

PMID- 9638255
TI  - [III. Physicians and their practice].

PMID- 9638256
TI  - The petrolingual ligament: the anatomy and surgical exposure of the
      posterolateral landmark of the cavernous sinus.
AB  - The petrolingual ligament is the posteroinferior attachment of the lateral wall
      of the cavernous sinus, where the internal carotid artery enters the cavernous
      sinus. The petrous segment of the internal carotid artery finishes and the
      cavernous segment begins at the superior margin of this ligament. The ligament is
      surgically important due to its identification as a landmark for dissection of
      the internal carotid artery during the approaches to posterolateral
      intracavernous and extracavernous lesions. It can be well exposed after
      mobilization of the gasserian ganglion, or after the trigeminal root and ganglion
      have been split along the junction of V2 and V3 (the transtrigeminal approach).
      The petrolingual ligament was studied in five cadaveric head specimens from ten
      sides. The size of the ligament was measured, and its anatomical, clinical and
      surgical importance is discussed.

PMID- 9638257
TI  - Supratentorial primitive neuroectodermal tumours: a report of four cases with an
      unusual clinical course in one patient.
AB  - Four children, who were treated for supratentorial primitive neuro-ectodermal
      tumours between 1986 and 1995 at Kyushu University Hospital, are here presented.
      The initial characteristic symptoms and signs of these patients included vomiting
      and headache, followed by motor weakness. All patients underwent direct surgery
      for their tumours while 2 also received a course of postoperative radio-therapy.
      After these treatments, 3 died within 4 months after diagnosis, whereas one
      infant, who underwent a total removal of the tumour but had no adjuvant therapy,
      is still alive after a follow-up period of 4 years. Most of the tumour cells of
      these 4 cases were poorly differentiated neuro-ectodermal cells, but some also
      showed variable differentiation along the glial and/or neuronal lines. While such
      differentiation had no impact on the clinical course of the patients, the
      malignant potential as assessed by the percentage of MIB1-positive cells showed a
      good correlation with the clinical features; the 3 cases with a rapid clinical
      course had MIB1 staining indices of more than 2%, and one case, who survived more
      than 4 years, had the same indices of 0.2% as found in benign tumours. Although
      "PNETs" of Hart and Earl share certain clinical features, they may be a group of
      tumours heterogeneous in their origins, histogenesis, and biological behaviours.

PMID- 9638258
TI  - Functional magnetic resonance mapping of sensory motor cortex for image-guided
      neurosurgical intervention.
AB  - PURPOSE: This paper describes the potentials of functional magnetic resonance
      imaging (fMRI) to map sensory motor cortex in patients with mass lesions near
      primary motor cortex and to guide neurosurgical procedures located close to
      eloquent brain regions. MATERIAL AND METHODS: 7 patients with mass lesions near
      the central sulcus and 10 healthy volunteers were studied using a blood
      oxygenation level dependent 2D multislice multishot T2* weighted gradient echo
      EPI sequence on a 1.5T Phillips Gyroscan during alternating epochs of rest and
      motor activation of hand, foot and tongue. Sites of neuronal activation were
      identified by statistical analysis of the signal time course using Kolmogorov
      Smirnov statistics. RESULTS: Neuronal activation following motor tasks
      consistently localised to the contralateral precentral gyrus and the
      supplementary motor area, even in the presence of local brain pathology.
      Additionally we could observe activation in primary sensory areas (post-central
      gyrus) and supplementary motor area (SMA) in some cases. CONCLUSION: fMRI is
      capable of mapping sensory motor cortex even in the presence of distorting brain
      lesions. Since this information will provide valuable information to the
      neurosurgeon during pre-operative planning, we consider this method for
      neurosurgical navigation a valuable tool in the routine diagnostic of
      intracerebral interventions.

PMID- 9638259
TI  - Haemodynamic evaluation of cerebral gliomas using XeCT.
AB  - The purpose of this study was to characterize regional blood flow (BF) in
      untreated cerebral gliomas (CG) using stable Xe-enhanced computed tomography
      (XeCT). XeCT of 38 patients with untreated CG were analyzed and compared with CT
      and magnetic resonance images (MRI) and histopathological findings. Individual
      averaged BF values for tumour in 29 high grade gliomas (HGGs) and 9 low grade
      gliomas (LGGs) were intermediate between averaged BF values for cortex and white
      matter in the non-tumour bearing hemisphere. All averaged BF values for cyst and
      central necrosis were very low. In 27 HGGs, BF in tumour was relatively high in
      ring-enhancement lesions on CT and MRI, but was low even in viable tumour centers
      showing no contrast enhancement. In the other 2 HGGs, BF was low in tumour center
      and relatively high in tumour periphery regardless of homogeneous enhancement. In
      5 HGGs, averaged BF value of the cortex outside surrounding oedema was higher
      than that of cortex in the non-tumour bearing hemisphere. In LGGs, BF
      distribution in tumour was homogeneously low in 3 small-sized and heterogeneous
      in 6 large-sized lesions including moderately high and low BF regions. These
      differences in BF pattern between HGGs and LGGs on XeCT might be helpful in
      considering to some extent the histopathology of untreated cerebral glioma pre
      operatively.

PMID- 9638260
TI  - Intraoperative facial nerve monitoring (IFNM) predicts facial nerve outcome after
      resection of vestibular schwannoma.
AB  - Intraoperative facial nerve monitoring (IFNM) is a suitable technique for
      intraoperative facial nerve identification and dissection, especially in large
      vestibular schwannomas (VS) (acoustic neuroma). To evaluate its feasibility for
      estimating functional nerve outcome after VS resection 60 patients underwent
      surgery using IFNM. Out of this group the last 40 patients were included in a
      prospective study evaluating the prognostic value of various IFNM parameters
      (proximal and distal absolute EMG amplitude, stimulation threshold, and proximal
      to-distal amplitude ratio) for prediction of initial postoperative facial nerve
      function and recovery of function. Stimulation threshold and absolute EMG
      amplitude proximally at the brain stem were both predictive for postoperative
      nerve function. Good initial facial nerve outcome (modified House Brackmann
      grading, mHB degree I and degree II) was found in 15/16 patients with a proximal
      EMG amplitude greater than 800 microV and in 19/22 patients with proximal
      stimulation threshold less than 0.3 mA. Sixteen of 16 patients with proximal
      stimulation threshold equal to or greater than 0.3 mA had moderate-to-severe
      facial palsy (mHB degree III or worse). Six of six patients without evokable
      proximal amplitude initially had insufficient nerve function (mHB degree IV).
      Intraoperative decrease of the proximal amplitude was associated with an
      unfavourable outcome, whereas distal amplitudes usually stayed unchanged. Mean
      distal EMG amplitudes were also found to be decreased with poor nerve function,
      which may mean that the tumour had already affected the nerve. A proximal
      amplitude of 300 microV or less and a proximal-to-distal amplitude ratio below
      1:3 were found in the absence of functional recovery in 6/8 (75%) and 5/6 (83%)
      patients with initial mHB degree IV, respectively. Two patients with initial mHB
      degree IV improved to mHB degree III despite intraoperative evidence of missing
      functional nerve integrity. Therefore, functional recovery cannot be predicted by
      IFNM in all cases of anatomical nerve preservation. We conclude that a minimum
      follow-up period of 1 year may still be advisable even in certain patients
      without evidence of intraoperative functional nerve integrity.

PMID- 9638261
TI  - Subjective complaints versus neuropsychological test performance after moderate
      to severe head injury.
AB  - Neuropsychological test performance and subjective complaints of 85 patients with
      moderate to severe head injury were investigated at 6 months postinjury. The
      neuropsychological test battery included 10 measures of attention, memory, mental
      flexibility, reaction time, visuoconstruction and verbal fluency. Subjective
      complaints were assessed using a self-report questionnaire subdivided into four
      subscales (somatic, cognitive, emotional and behavioural). Ratings were obtained
      for the pre-injury and current status. Thirty-three trauma patients with injuries
      to other parts of the body than the head were used as controls. For the head
      injured, relatives also completed the questionnaire. Head injured patients
      performed significantly below trauma control patients on nearly all test
      measures. Head injured patients and their relatives reported a significant
      increase in subjective complaints since the injury on all four subscales, with no
      differences between patients' and relatives' reports. These changes were also
      reported by the trauma controls, but they report fewer changes in somatic and
      cognitive functioning. Exploratory canonical correlation analyses revealed no
      correlations between any of the four scales of the questionnaire and the test
      measures, nor for the head injured, the trauma controls, or the relatives,
      indicating no relevant relationship between subjective complaints and
      neuropsychological test performance.

PMID- 9638262
TI  - Profuse hemorrhage from cerebral vessels in tangential missile injuries.
AB  - Tangential missile injuries are recognized as a cause of cerebral damage by in
      driven bone fragments, parenchymal lacerations and intracerebral haematomas.
      Severe blood loss from this type of injury was not reported. Four patients are
      described in whom high kinetic energy missiles caused severe tangential
      craniocerebral injuries. Their condition was aggravated by life threatening
      haemorrhage. The bleeding vessels were cerebral arteries or major veins entrapped
      in the fracture line and bleeding extracranially. This blood loss cannot be
      controlled by dressing and salvage could be achieved only by immediate
      resuscitation, vigorous fluid replacement and very rapid evacuation to a
      neurosurgical center.

PMID- 9638263
TI  - Local hypercoagulative activity precedes hyperfibrinolytic activity in the
      subdural space during development of chronic subdural haematoma from subdural
      effusion.
AB  - The involvement of coagulation and fibrinolysis in the development of chronic
      subdural haematoma (CSH) from subdural effusion was investigated. Subdural fluid
      and venous blood samples were obtained from 34 patients with CSH and 9 patients
      with subdural effusion, and analyzed using enzyme-linked immunosorbent assays for
      thrombin-antithrombin III complex (TAT), prothrombin fragment F1 + 2 (F1 + 2),
      tissue factor, tissue factor pathway inhibitor (TFPI) and D-dimer. CSH was
      classified into the layering type, believed to be active, and other types
      according to x-ray computed tomography. All markers in the blood of both patient
      groups were similar to the values of normal subjects. Levels of TAT and F1 + 2
      were much higher in the subdural fluid than in the blood of patients with CSH (P
      < 0.001, P < 0.001) and with subdural effusion (P < 0.05, P < 0.05). The level of
      D-dimer in the subdural fluid was significantly higher than in the blood (P <
      0.001) in patients with CSH, but not in patients with subdural effusion. All
      markers in the subdural fluid of layering type CSH, except TFPI, were
      significantly higher than in the other types (P < 0.05). Local hypercoagulative
      activity in the subdural space is present in subdural effusion and precedes
      hyperfibrinolytic activity in CSH. Thrombin generation as indicated by TAT and F1
      + 2 might be involved in the development of CSH. Propagation of CSH may be
      modulated by the coagulation system including the extrinsic pathway and
      fibrinolysis.

PMID- 9638264
TI  - A surgical technique for a vertebral column autograft using the intervertebral
      disc for cervical disc disease.
AB  - We describe a surgical technique for a vertebral column autograft using the
      intervertebral disc for cervical disc disease for patients whose major problem is
      not spinal instability. Of a total of 41 patients with cervical disc disease
      suffering from cervical spondylotic radiculomyelopathy, 33 patients were operated
      on at one level and 8 patients were operated on at two levels. Postoperative X
      ray film showed some movement at the "operated" disc level in all patients
      (average postoperative follow-up period was 43 months, range two years to 5
      years). A significant decrease in motion in the extension position was observed
      postoperatively (p < 0.0001), but no significant difference was observed between
      the preoperative motion and the postoperative motion in the flexion position.
      Anterior angulation was found in two (5%) of the 41 patients. This surgical
      procedure has two major advantages: 1) no complications related to the iliac
      donor site, allowing early patient mobilization; 2) the extensive posterior spur
      can be removed safely and easily under a wide operative field. We believe that
      this surgical procedure is suitable for preserving the mobility of the spine and
      may avoid stress concentration at adjacent levels of the "operated" disc.
      However, in patients whose major problem is spinal instability, anterior cervical
      fusion should be performed.

PMID- 9638265
TI  - Cellular dynamics of macrophages and microglial cells in reaction to stab wounds
      in rat cerebral cortex.
AB  - To examine the cellular dynamics of macrophages and microglial cells in response
      to cerebral injury, we studied the brain adjacent to cortical stab wounds in
      young adult rats. Brains were obtained 30 min after intravenous infusion of
      bromodeoxyuridine (BrdU) on one day (day 1) to 28 days (day 28) after wounding.
      Brain sections were double-labelled immunohistochemically for monocyte/macrophage
      antigen ED1 and for BrdU. ED1-positive (ED1+) cells were classified
      morphologically into two groups, ED1+L and ED1+S cells, representing macrophages
      and microglial cells, respectively. ED1+L cells appeared on day 1 after wounding
      and rapidly increased in number to reach a maximum on day 3, but quickly
      disappeared by day 5. ED1+S cells also appeared on day 1, but the increase in
      number was slower, reaching a maximum only on day 7. ED1+L cells were all
      negative for BrdU, but some ED1+S cells were stained for BrdU, evidence of
      proliferation. The present investigation demonstrated different cellular dynamics
      for macrophages and microglial cells responding to a stab wound, and also
      indicated differing sources for the two cell type. It may be possible to prevent
      the accumulation of these cells which are harmful to the brain in reducing the
      damage suffered.

PMID- 9638267
TI  - Intraspinal air: an unusual finding of cervical epidural abscess.

PMID- 9638266
TI  - Multiple intracerebral haemangioblastomas in identical twins with von Hippel
      Lindau disease--a clinical and molecular study.
AB  - Von Hippel-Lindau (VHL) disease is an inherited autosomal dominant neoplastic
      disorder causing central nervous system haemangioblastomas. The VHL gene (3p25
      3p26) is known to be a tumour suppressor gene, with its inactivation being
      responsible for a predisposition to tumour development. As far as we know, the
      present report of VHL disease manifestation in identical twins is unique. Genetic
      inquiry into the family background did not reveal this disease among their
      progenitors. For presymptomatic diagnosis of 17 presently unaffected family
      members, constitutional DNA of the twins was screened for VHL germline mutations,
      using loss of heterozygosity studies and exon-specific DNA sequencing. To
      determine the influence of somatic mutations of the VHL gene in tumourigenesis,
      DNA of five surgically removed intracerebral haemangioblastomas of the identical
      twins was analyzed in comparison with their constitutional DNA by DNA sequencing
      of the complete VHL coding region. However, no allelic losses were found for the
      VHL gene or for various other tumour suppressor genes (p53, BRCA1, BRCA2, DCC,
      and MCC). Furthermore, no mutations were found in the constitutional DNA of
      either twin sister or in the DNA of all five tumour lesions. Based on our
      observations, we conclude that in certain VHL families, presymptomatic molecular
      diagnosis of the disease is not feasible and requires close clinical surveillance
      of all individuals at risk.

PMID- 9638268
TI  - Mycotic aortic aneurysm presenting as multiple cerebral abscesses.
AB  - A 68-year-old male presented with multiple cerebral abscesses. Possible
      intrathoracic embolic sources were not detected by echocardiography and chest
      radiography and the main lesion was surgically excised. Following deterioration
      of the neurological status, computerized tomography performed 2 weeks later
      revealed a mycotic aneurysm of the ascending aorta, probably related to a
      previous cardiac operation. This is the first case in the literature of aortic
      infection presenting as multiple brain abscesses.

PMID- 9638269
TI  - Psammomatous meningioma arising from the diaphragma sellae.

PMID- 9638270
TI  - A case of non-functioning pituitary adenoma accompanied by a large cyst.

PMID- 9638271
TI  - Haematological changes in N'Dama and Gobra Zebu bulls during Trypanosoma
      congolense infection maintained under a controlled feeding regimen.
AB  - Haematological changes were monitored in Gobra-Zebu and N'Dama bulls following
      infection with Trypanosoma congolense. The cattle were offered a diet which
      provided levels of protein and energy above maintenance requirement and a pair
      feeding regimen was used in order to eliminate the confounding anorexic effects
      of trypanosomosis on the traits studied. Packed red cell volume (PCV), red blood
      cells (RBC) and haemoglobin (Hb) were monitored weekly. Mean corpuscular
      haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), and mean
      corpuscular volume (MCV) were derived by computation. Significant breed
      differences (P < 0.001) were observed in the baseline data collected with N'Dama
      bulls having higher (P < 0.001) values for RBC and Hb. PCV levels were similar in
      both breeds pre-infection. Post-infection, there was a significant (P < 0.001)
      infection effect on the RBC, Hb and PCV in both breeds. The pathogenic effects
      were more severe in the Gobra-Zebu bulls where three out of ten bulls compared
      with only one out of eight infected N'Dama bulls attained the low PCV threshold,
      treated and withdrawn from the study along with their pair mates. Throughout the
      infection in N'Dama cattle and during the first 6 weeks of infection in the Gobra
      Zebu bulls, the infection presented a normochromic normocytic anaemia. However,
      in the chronic phase, the Gobra-Zebu bulls became macrocytic. The infection
      reduced total dry matter intake in both breeds although this persisted longer in
      the Gobra-Zebus. However, their pair-fed controls showed no haematological
      changes indicating that the anorexia was not compounding the effects of the
      infection. The severity and type anaemia in N'Dama correlates with their innate
      ability to resist the effects of trypanosome infection compared to the Gobra-Zebu
      bulls.

PMID- 9638272
TI  - The genomic fingerprinting of the coding region of the beta-tubulin gene in
      Leishmania identification.
AB  - We have demonstrated the polymorphism of the beta-tubulin gene region in
      Leishmania and its value in the identification of the parasite. In this work we
      have shown that the coding region of the gene has sufficient variation to
      accurately discriminate these parasites at the subgenus level. Nevertheless,
      intrasubgenus diversity, for particular restriction enzymes, was found in New
      World Leishmania belonging to the Leishmania subgenus. For instance, differences
      were found between mexicana and amazonensis strains. A unique pattern at the
      species level was found in particular species of both subgenera, e.g. L. (L.)
      major strain P and L. (L.) tropica belonging to the Leishmania subgenus, and L.
      (V.) panamensis strain LS94 from the Viannia subgenus. Particular endonucleases
      are diagnostic in Leishmania species discrimination as in the case of PvuII for
      the mexicana and amazonensis. This variation evidenced in the beta-tubulin gene
      region of Leishmania also occurred in other Kinetoplastida e.g. Trypanosoma
      cruzi, Leptomonas spp. and Crithidia spp. Moreover, these organisms showed a
      different genomic fingerprinting for the beta-tubulin gene among them and also
      Leishmania. Thus, the polymorphism of the coding region of the beta-tubulin gene
      can be used as a molecular marker for the identification of Leishmania.

PMID- 9638273
TI  - Activity of N,N-dimethy-1-2-propen-1-amine derivatives in mice experimentally
      infected with Trypanosoma cruzi.
AB  - Propenamine derivatives 3-(4'-bromo-[1,1'-biphenyl]-4-yl)-3-(4-X-phenyl)-N,N
      dimethyl-2-prope n-1-amine (where X = H or Br) were tested in experimentally
      infected mice with Trypanosoma cruzi (Y strain). When a daily dose of 20 mg kg-1
      of the bromo (X = Br) derivative for 9 consecutive days was used, no parasite by
      optical microscopy was found. Significant parasitemic decrease was also observed
      with a single dose (100 mg kg-1) of this compound. Moreover, both treatment
      schemes displayed a strong protective effect characterized by decreased of
      mortality. On the other hand, similar treatment schedules using the unsubstituted
      (X = H) derivative led to parasitemic and mortality curves similar to the control
      group. These results indicate that the bromo derivative has a remarkable activity
      against T. cruzi infection. Due to the potentiality of this derivative, further
      investigation of this class of compounds as chemotherapeutic agents for Chagas'
      disease is of prime importance.

PMID- 9638274
TI  - Relationship between Borrelia burgdorferi sensu lato species, red squirrels
      (Sciurus vulgaris) and Ixodes ricinus in enzootic areas in Switzerland.
AB  - The infection and reservoir status of red squirrels (Sciurus vulgaris) for
      Borrelia burgdorferi sensu lato were studied in Switzerland. B. burgdorferi sensu
      lato was isolated from 15 skin samples from 4/6 dead red squirrels, victims of
      road traffic. Isolates were identified using restriction fragment length
      polymorphism (RFLP): B. burgdorferi sensu stricto was present in 14 culture tubes
      containing skin samples and B. afzelii in two other tubes. A mixed infection was
      revealed in one case. A total of 227 ticks attached to squirrels were cultivated
      in BSKII medium and 90 isolates were obtained. Genotypic identification by RFLP
      showed that B. afzelii (59%) and B. burgdorferi sensu stricto (46%) dominated in
      ticks feeding on red squirrels. Data collected from one particular animal, highly
      infested with Ixodes ricinus and harbouring numerous Borrelia-infected Ixodes
      ricinus ticks, showed that transmission of B. burgdorferi sensu lato occurred
      from S. vulgaris to feeding ticks. More precisely, B. burgdorferi sensu stricto
      and B. afzelii were mainly transmitted from S. vulgaris to ticks. The present
      data emphasized the results obtained previously from small rodents and birds in
      Japan and in Switzerland, showing the occurrence of specific associations between
      host species and Borrelia genospecies.

PMID- 9638275
TI  - Cutaneous and subcutaneous granulomata formation in mice immunized and challenged
      with third-stage infective hookworm (Ancylostoma caninum) larvae.
AB  - To determine the inflammatory and immunological mechanisms associated with live
      third-stage (L3) hookworm larval vaccines, mice were immunized either
      subcutaneously or orally with three doses of 500 L3 of Ancylostoma caninum at 2
      week intervals, and then challenged percutaneously (via abdominal skin) with 500
      L3. Non-immunized mice served as negative controls. Skin was excised from post
      challenge mice at intervals between 6 h and 28 days, and then examined by light
      microscopy. In non-immunized mice the L3 exhibited no structural damage and
      infiltrating inflammatory cells were absent from the surrounding tissues. There
      were no changes in the cutaneous architecture. In contrast, skin recovered from
      the immunized mice was edematous and exhibited marked inflammatory changes with
      resultant destruction of the challenge L3. At 6 h post-challenge the L3 exhibited
      cuticular swelling and damage; the surrounding tissue was infiltrated by
      polymorphonuclear inflammatory cells. By 24 h granulomata in the dermis,
      subcutaneous tissues and underlying abdominal muscles were first observed
      surrounding dead L3. The number of granulomata peaked at 72 h, with the majority
      distributed in the subcutaneous tissues. Plasma cells predominated in the early
      granulomata, but by 3-7 days post-challenge foreign body giant cells began to
      appear. In some cases, intact and presumably living L3 were noted in the
      abdominal muscles 14-28 days post-challenge, which suggested that protection
      against larval challenge was not absolute. Granuloma formation appears to be a
      major component of the post-vaccination murine host immune response against
      challenge larvae. The observation generates several hypotheses to investigate the
      mechanisms of protection afforded by living helminth vaccines.

PMID- 9638276
TI  - Biological characterization and genetic diversity of Mexican isolates of
      Trypanosoma cruzi.
AB  - The present work reports the in vitro biological characterization of 17
      Trypanosoma cruzi isolates from southern and central Mexico, and compares these
      results to those of four South American strains and one clone from Brazil. The
      parameters evaluated were growth rates, percentage of parasites undergoing
      transformation from epimastigotes to trypomastigotes, infectivity to, and in
      vitro killing of cultured Vero and P388 cells. Isoenzyme patterns of 11 enzymatic
      systems and 16 loci were also determined for the Mexican isolates. The parasites
      showed differences in growth, depending if they were cultured in LIT with hemin
      or in Grace's media. Transformation was obtained only in Grace's medium and
      differences were observed between the stocks. Stocks Z10 and Z21 showed the
      highest percentage of transformation within the Mexican isolates (39 and 41%,
      respectively). A second group showed percentages of transformation between 15 and
      28%. In contrast, the South American strains showed higher rates of
      transformation (36-65%). Infection of cultured cells by isolates Z10 and H5 was
      evaluated in both Vero and P388 cells. Differences were observed both in the
      percentage of infected cells as well as in the number of amastigotes per cell.
      Differences in the ability to cause in vitro killing of P388 cells were also
      observed among the isolates. Isoenzyme analysis revealed genetic variation
      between the isolates, each of them with an unique zymodeme. This genetic analysis
      revealed, in general, a clustering based on the geographical origin of the
      isolates. Finally, correlation with clinical symptoms is discussed.

PMID- 9638277
TI  - Causal prophylactic activity of antihistaminic agents against Plasmodium yoelii
      nigeriensis infection in Swiss mice.
AB  - The causal prophylactic activity of five tricyclic anti-histaminic agents
      (histamine H1-receptor antagonists) cyproheptadine, ketotifen, loratadine,
      azatadine and terfenadine was evaluated in an experimental murine malaria model.
      Sporozoite induced infections with Plasmodium yoelii nigeriensis (N-67), a strain
      innately resistant to choloroquine, were employed for the efficacy test and
      pyrimethamine and primaquine were used as standard reference drugs. Treatment
      with cyproheptadine or ketotifen at 5 mg/kg and terfenadine at 50 mg/kg, orally
      for 3 days (-1, 0, +1) completely prevented the establishment of patent infection
      in mice inoculated with 1 x 10(5) sporozoites on day 0. Partial activity was
      recorded with lower doses of the above agents as well as with azatadine and
      loratadine at 10 mg/kg as indicated by marginal delay in the development of
      patent infection after sporozoite challenge. None of these agents showed blood
      schizontocidal activity at doses found effective in the causal prophylactic test,
      though initial suppression of parasitaemia was observed with cyproheptadine and
      ketotifen at higher doses. This study is the first report on efficacy of
      antihistaminic agents for growth inhibition of pre-erythrocytic stages of any
      malaria parasite.

PMID- 9638278
TI  - Response of a T. b. rhodesiense stock with reduced drug susceptibility in vitro
      to treatment in mice and cattle.
AB  - In vivo drug susceptibility tests involving treatment of infected mice and cattle
      were performed on two trypanosome stocks, a T. brucei brucei and a T.b.
      rhodesiense, isolated in South Eastern Uganda. The T. b. rhodesiense stock had
      expressed reduced susceptibility to diminazene aceturate and isometamidium
      chloride in vitro, while the other, a T. b. brucei stock was susceptible.
      Diminazene aceturate at 14 mg/kg was not sufficient to cure all T. b. rhodesiense
      infected mice. Similarly, in the case of isometamidium chloride, 33% of infected
      mice treated with 2.0 mg/kg drug were not cured. In contrast, mice infected with
      the susceptible T. b. brucei and treated similarly with either drug were all
      cured. However, when cattle infected with the T. b. rhodesiense stock, or the
      susceptible T. b. brucei stock, or a 1:1 mixture of the two were treated with 7
      mg/kg diminazene aceturate, they were all cured. Use of diagnostic PCR employing
      T. brucei specific primers confirmed that although the cattle had acquired
      infection pre-treatment, no trypanosome DNA amplification signal was demonstrated
      in the samples collected 60 days post-treatment. The reduced susceptibility of
      this T. b. rhodesiense, which could be demonstrated in mice as well as in
      culture, may indicate the existing potential for evolution of resistance in South
      Eastern Uganda.

PMID- 9638279
TI  - Gulf War syndrome--a model for the complexity of biological and environmental
      interaction with human health.
AB  - Since the end of the Gulf War, tens of thousands of American, Canadian and
      British soldiers who participated in that war have claimed to be suffering from a
      variety of incapacitating symptoms which are generally termed as Gulf War
      Syndrome (GWS). The symptoms are multiple but mainly consist of excessive
      tiredness, muscle and joint pain, loss of balance, sensory symptoms,
      neurobehavioural manifestations, diarrhoea, bladder dysfunction, sweating
      disturbances, and respiratory, gastrointestinal, musculoskeletal and skin
      manifestations. These veterans have been exposed to a variety of damaging or
      potentially damaging risk factors including environmental adversities, pesticides
      such as organophosphate chemicals, skin insect repellents, medical agents such as
      pyridostigmine bromide (NAPS), possible low-levels of chemical warfare agents,
      multiple vaccinations in combinations, depleted uranium, and other factors. A
      large number of basic research findings, clinical epidemiological studies, and
      case control studies are reviewed to try and link them together to produce a
      coherent picture and to demonstrate the complexity of the interaction of
      biological systems, environmental and genetic factors, combinations of drugs and
      toxins with human health. The findings of these studies so far have demonstrated
      that many of the previous assumptions made about the 'safety' of certain drugs
      and toxic substances or vaccines must be radically reviewed. Many of the findings
      have far reaching implications not only in terms of explanation of what might
      have gone wrong during the Gulf War, but also have wider implications for many
      occupational groups who are exposed daily to some of these risk factors. More
      open-mindedness and much less prejudice are required concerning the basic biology
      of interactions of the above factors and their effects on cell functions and
      wider intelligent research is urgently required with high priority. This review
      highlights the importance of intelligent research for answers for a new
      phenomenon, and demonstrates the necessity for a combination of this approach
      with high quality epidemiological research. The reader will notice an emerging
      clear picture that the majority (if not all) of these advances have been achieved
      from studies funded by independent or charity organizations rather than by the
      responsible authorities who are supposed and are duty bound to take on this task.

PMID- 9638281
TI  - Status of peer review.

PMID- 9638280
TI  - The evolution of human medicines control from a national to an international
      perspective.

PMID- 9638282
TI  - Emerging infectious diseases: can we meet the challenge?
AB  - Demonstration of quality health care includes documentation of outcomes of care.
      Surveillance is a comprehensive method of measuring outcomes and related
      processes of care, analyzing the data, and providing information to members of
      the health care team to assist in improving those outcomes. Surveillance is an
      essential component of effective clinical programs designed to reduce the
      frequency of adverse events such as infection or injury.

PMID- 9638283
TI  - Risk index for prediction of surgical site infection after oncology operations.
AB  - INTRODUCTION: Several studies have shown that surgical site infections represent
      most hospital-acquired infections, with the major impact being on average
      hospital stay and cost of hospitalization. METHODS: To develop a risk model for
      prediction of surgical site infections in cancer patients undergoing operative
      procedures and identify those with high probability of infection we performed a
      prospective cohort study in a tertiary cancer care hospital in Rio de Janeiro,
      Brazil. Risk factors were studied in single and multivariate analyses. RESULTS:
      Over a 24-month period, 1205 patients underwent operations for malignant disease.
      The overall surgical site infection rate was 17.3%. A multivariate stepwise
      logistic regression model identified six independent predictive risk factors:
      contaminated and infected operations, surgical duration greater than 280 minutes,
      male sex, prior radiotherapy, American Society of Anesthesiology class III to V,
      and antimicrobial prophylaxis not according to protocol. On the basis of
      individual risk scores, two groups of patients were identified: a low-risk (score
      < or = 8; surgical site infection rate 10%) and a high-risk group (score > or =
      9; surgical site infection rate 33.6%; relative risk 3.4; 95% confidence interval
      2.6 to 4.4). CONCLUSION: The oncology risk model allowed for the identification
      of a high-risk score group of patients and implementation of a more efficient and
      selective intervention program.

PMID- 9638284
TI  - Evaluation of infection control parameters according to the 1994 Centers for
      Disease Control and Prevention Tuberculosis guidelines: a 2-year experience.
AB  - BACKGROUND: Because of classification as a high-risk institution for potential
      Mycobacterium tuberculosis exposure and an employee purified protein derivative
      conversion rate of 2.7%, a large university-affiliated county hospital enhanced
      administrative and engineering controls, as recommended by its tuberculosis task
      force in early 1994. METHODS: For 1994 and 1995 the medical records of all
      patients with culture-confirmed M. tuberculosis were reviewed according to the
      1994 Centers for Disease Control and Prevention guidelines for case surveillance
      and risk assessment (infection control parameters). The chi 2-test was used to
      compare 1994 and 1995 infection control parameters for statistical significance
      (p < or = 0.05). RESULTS: In 1994 and 1995 there were 253 patients with
      tuberculosis, 85% of whom (214/253) had pulmonary-site tuberculosis. The
      "representative" patient with pulmonary tuberculosis was profiled, along with
      institution-specific surveillance data on diagnostics, medication regimens, and
      airborne isolation practices. Between 1994 and 1995 there was a trend toward
      increased numbers of homeless patients with tuberculosis, from 8.2% to 17% (p =
      0.07). Decreases in the numbers of HIV seropositive patients with tuberculosis
      from 35% in 1994 to 24% in 1995 (p = 0.2) and of jailed patients with
      tuberculosis from 9.8% to 5% (p = 0.5) were not significant. Drug-resistance
      patterns increased from 13% to 24%, with borderline significance (p = 0.06). The
      employee purified protein derivative testing compliance rate increased from 49%
      in 1994 to 74% in 1995, with the purified protein derivative conversion rate also
      increasing from 2.7% to 3.5%. CONCLUSION: The infection control parameter data
      were beneficial in identification of institution-specific risk factors for our
      population with tuberculosis. Although labor-intensive, the annual tuberculosis
      reports supported requests for administrative and engineering controls; however,
      efficacy of the 1994 tuberculosis control plan was difficult to assess from
      purified protein derivative conversion rates alone, because the testing
      compliance rate also increased.

PMID- 9638285
TI  - An effectiveness and cost analysis of presumptive treatment for Mycobacterium
      tuberculosis.
AB  - BACKGROUND: Delay in treatment of tuberculosis has contributed to both the spread
      of tuberculosis and its case fatality rate. METHODS: Decision analysis was used
      to examine the effectiveness and cost of presumptive treatment in patients
      evaluated for tuberculosis. RESULTS: Over a range of assumptions, empiric
      antituberculous therapy for acid-fast bacillus smear-positive persons lowers
      mortality and cost per person evaluated when available rapid diagnostic
      laboratory methods for tuberculosis are used. In contrast, the average cost per
      life saved by giving presumptive treatment to all acid-fast bacillus smear- and
      HIV-negative patients exceeds. $1 million. Empiric treatment for HIV-infected
      patients with acid-fast bacillus-negative smears decreases average mortality by
      2% at an additional cost of $8000 per life saved. When the prevalence of multiple
      drug resistance exceeds 9.6%, presumptive drug-resistant therapy for acid-fast
      bacillus smear-positive patients, rather than the initial four-drug regimen
      recommended for much of the United States, minimizes both mortality and costs.
      CONCLUSIONS: Empiric antituberculous therapy often minimizes average mortality
      and cost for patients evaluated for tuberculosis when rapid diagnostic methods
      are used.

PMID- 9638286
TI  - A survey of infection control professional staffing patterns at University
      HealthSystem Consortium institutions.
AB  - BACKGROUND: Proper staffing of infection control departments has long been a
      topic of interest. The most complete report on the subject, the Study on the
      Efficacy of Nosocomial Infection Control, was published in 1985. To provide
      current benchmarking comparison data for expected staff reductions at the
      University of Michigan Health System, a survey of University HealthSystem
      Consortium members was performed. METHODS: A survey tool was developed to obtain
      general demographic, staffing, and case-mix information. An infection control
      professional at each institution was contacted to obtain most of the information.
      Additional information was obtained from standard references. RESULTS: Responses
      were obtained from 45 University HealthSystem Consortium members (67%). Full-time
      equivalent ratios were based on the following parameters and compared for the
      institutions: number of occupied beds (according to occupancy rate, median 137
      occupied beds/full-time equivalent), number of intensive care unit beds (median
      28 beds/full-time equivalent), number of admissions or discharges (median 6686
      admissions/full-time equivalent), number of ambulatory care visits (median
      104,426 visits/full-time equivalent), and case-mix index (median 1.75).
      CONCLUSIONS: Many institutions are using benchmarking comparison data to make
      decisions regarding staff reductions. This survey provides preliminary data for
      determining the "best practice" in staffing for infection control departments.
      More information may be needed to evaluate other factors that affect infection
      control professionals' workload.

PMID- 9638287
TI  - Behavioral interventions to improve infection control practices.
AB  - No single intervention has been successful in improving and sustaining such
      infection control practices as universal precautions and handwashing by health
      care professionals. This paper examines several behavioral theories (Health
      Belief Model, Theory of Reasoned Action and Theory of Planned Behavior, self
      efficacy, and the Transtheoretic Model) and relates them to individual factors,
      also considering interpersonal and organizational factors. Further, this article
      includes recommendations of individual and organizational components to be
      addressed when planning a theoretically based intervention for improving
      infection control practices. A hypothetic framework to enhance handwashing
      practice is proposed.

PMID- 9638288
TI  - Wound infections after hysterectomy: opportunities for practice improvement.
AB  - BACKGROUND: This study was designed to determine the frequency of surgical site
      infection development after discharge from the hospital after abdominal or
      vaginal hysterectomy and the frequency of use of antimicrobial prophylaxis in
      this patient group. METHODS: A prospective cohort study was performed on patients
      undergoing abdominal or vaginal hysterectomy between February 1 and December 31,
      1995. Surgeons were contacted 1 month after the operations to determine which
      patients had acquired surgical site infections. Surgical site infection rates
      were calculated according to procedure, surgeon, and National Nosocomial
      Infection Surveillance system risk categories. A retrospective pharmacy record
      review was conducted to determine antimicrobial prophylaxis use according to
      procedure and surgeon. RESULTS: A total of 763 cases were surveyed; 55 (7.2%) met
      criteria for postoperative surgical site infection (7.7% abdominal and 4.5%
      vaginal hysterectomy). National Nosocomial Infection Surveillance system moderate
      risk patients had significantly higher infection rates than did low-risk patients
      for both abdominal (p = 0.045) and vaginal (p = 0.05) procedures. Most patients
      (71.1%) were not given antimicrobial prophylaxis. There was a wide range of
      antimicrobial prophylaxis use by surgeon (3.6% to 94.4% of patients, p < 0.01).
      CONCLUSION: Despite long-standing and widespread recommendations for
      antimicrobial prophylaxis before hysterectomy, most of our patients were operated
      on without such prophylaxis. Surveillance programs permit detailed review of
      patient care practices that may reveal opportunities for improvement.

PMID- 9638289
TI  - Costs of implementing a tuberculosis control plan: a complete education module
      that uses a train-the-trainer concept.
AB  - BACKGROUND: Tuberculosis once was thought to be nearly eradicated, but there was
      a 14% increase in cases of tuberculosis between 1985 and 1993, although decreases
      were observed in both 1994 and 1995. To reduce spread of this disease, health
      care workers must be familiar with tuberculosis, its signs, symptoms, and modes
      of transmission. In October 1994 the Centers for Disease Control and Prevention
      issued "Guidelines for Preventing the Transmission of Mycobacterium tuberculosis
      in Health Care Facilities." The combination of persistently high tuberculosis
      case rates, the development of multidrug-resistant tuberculosis, the new Centers
      for Disease Control and Prevention recommendations, and Occupational Safety and
      Health Administration enforcement has mandated large-scale training in health
      care facilities. METHODS: A tuberculosis control plan was developed and the train
      the-trainer concept was selected after review of the hospital's tuberculosis risk
      assessment, staff members requiring training, and available teaching staff. The
      training program that was developed included tuberculosis pathology and
      transmission, national and local epidemiology, placement and evaluation of skin
      tests, and an algorithm to assist in determining when isolation is indicated.
      RESULTS: One hundred forty-six trainers were trained in 4 days. During the next
      quarter, 66% (1989/3000) of staff members requiring instruction were trained. The
      total cost involved in development and training was approximately $26,000 and
      involved 1600 person-hours. CONCLUSION: Tuberculosis training should be directed
      toward high-risk areas, including intensive care units, emergency departments,
      and acute medicine wards. Large-scale training is time-consuming and expensive.
      Evaluation remains difficult. To facilitate compliance, pretest and posttest
      results should be provided, linked to Occupational Safety and Health
      Administration compliance and quality indicators for the hospital.

PMID- 9638290
TI  - Effect of several interventions on the frequency of handwashing among elementary
      public school children.
AB  - BACKGROUND: The purpose of this educational project was to assess the effect of
      several interventions on the frequency of handwashing among elementary public
      school children. METHODS: Participants in this project were first-graders and
      fourth-graders from jurisdictions within a mid-Atlantic metropolitan area. Phase
      I included a baseline assessment of bathroom cleanliness as well as adequacy of
      supplies for handwashing in each school. During phase 2, the frequency of
      handwashing before lunch or after bathroom use was monitored and recorded during
      a 2-month period. The schools were separated into four groups: a peer education
      group, a hand wipes and instructional poster group, a combination of the
      education and hand wipes/poster groups, and a (control) comparison school.
      RESULTS: Overall, a significant increase occurred in the proportion of
      handwashing frequency from preintervention to postintervention for each
      intervention group (wipes: 0.50 vs 0.66, p = 0.03; education only: 0.64 vs 0.72,
      p = 0.02; and education and wipes: 0.45 vs 0.67, p = 0.03) but not in the control
      group (0.42 vs 0.46, p = 0.26). When the first 3 weeks and the last 3 weeks after
      intervention were compared, handwashing frequency remained unchanged in the wipes
      only group (0.66 vs 0.66, p = 0.96), decreased in the education group (0.77 vs
      0.65, p = 0.006), and increased in the education and wipes group (0.58 vs 0.75, p
      = 0.003), as well as in the control group (0.37 vs 0.52, p = 0.01). CONCLUSION:
      Education combined with accessible convenient hand hygiene may result in a
      sustainable increase in the frequency of handwashing among elementary school
      children.

PMID- 9638291
TI  - Tuberculosis control in New York City hospitals.
AB  - OBJECTIVES: To assess the implementation of tuberculosis (TB) control measures in
      New York City hospitals in 1992 and determine trends during the subsequent 2
      years. METHODS: The 22 acute care facilities with the largest number of
      hospitalized TB patients in 1991 were selected for inclusion in the study.
      Medical and laboratory records of the 10 most recent acid fast bacilli (AFB)
      smear-positive patients in each of the selected facilities in 1992, 1993, and
      1994 were reviewed by using a standardized questionnaire to determine risk
      factors for TB, previous history of TB, clinical signs and symptoms, AFB
      laboratory turnaround times, emergency department contact, timing of isolation,
      timing of treatment, case reporting, and status on discharge. The patients' rooms
      were evaluated for TB environmental control measures if the patient was still on
      respiratory isolation precautions. RESULTS: More than one third of patients were
      admitted with a previous history of TB, 31% were admitted with a cavitary lesion
      on chest x-ray examination, and 48% were known to have HIV infection. Eighty-five
      percent were admitted from the emergency department where they stayed for up to
      116 hours (mean stay: 17 hours). The proportion of patients placed in AFB
      isolation on admission to the floor increased from 75% in 1992 to 84% in 1994.
      The proportion of patients given a minimum of four anti-TB drugs increased from
      88% in 1992 to 94% in 1994. Patients "on isolation" were sharing rooms with up to
      nine other patients in 1992, whereas no patients were sharing rooms in the 1994
      survey. In 1992, 51% of the rooms were under negative air flow with respect to
      the corridor. During the 1994 survey, 80% of rooms were under negative air flow.
      Between 1992 and 1994, the proportion of AFB isolation rooms with dust/mist
      respirators increased from 28% to 76% (p < 0.00001). Approximately 25% of
      discharged patients left against medical advice (no trend over time). The
      proportion of medically discharged patients with three negative AFB smears before
      discharge increased from 26% to 48% (p = 0.03) and the proportion referred for
      directly observed therapy increased from 15% to 53% (p = 0.00001). CONCLUSION: TB
      control efforts in New York City hospitals improved dramatically between 1992 and
      1994. The ultimate control of TB will continue to depend on the coordinated
      efforts within and between health care facilities, providers, and the community.

PMID- 9638292
TI  - Recommended practices for surveillance. Association for Professionals in
      Infection Control and Epidemiology, Inc. Surveillance Initiative working Group.
AB  - Demonstration of quality health care includes documentation of outcomes of care.
      Surveillance is a comprehensive method of measuring outcomes and related
      processes of care, analyzing the data, and providing information to members of
      the health care team to assist in improving those outcomes. Surveillance is an
      essential component of effective clinical programs designed to reduce the
      frequency of adverse events such as infection or injury. Although there is no
      single or "right" method of surveillance design or implementation, sound
      epidemiologic principles must form the foundation of effective systems and must
      be understood by key participants in the surveillance program and supported by
      senior management. Teamwork and collaboration across the health care spectrum are
      important for the development of surveillance plans. Each health care
      organization must tailor its surveillance systems to maximize resources by
      focusing on population characteristics, outcome priorities, and organizational
      objectives. To ensure quality of surveillance, the following elements must be
      incorporated: A written plan should serve as the foundation of any surveillance
      program. The plan should outline important objectives and elements of the
      surveillance process so that resources can be targeted appropriately.
      Thoroughness or intensity of surveillance for an area of interest must be
      maintained at the same level over time. Fluctuations of a surveillance rate have
      no meaning unless the same level of data collection is maintained. External rate
      comparisons are meaningless unless the systems used have comparable intensity.
      All the elements of surveillance should be used with consistency over time. This
      includes application of surveillance definitions and rate calculation methods.
      Personnel resources need to be appropriate for the type of surveillance being
      performed. This includes trained professionals who understand epidemiology and
      who have access to continuing professional education opportunities. Other
      resources essential to surveillance include computer support, information and
      technology services, clerical services, and administrative understanding and
      support to maintain a quality program. As a means of quality control and to
      ensure accuracy, the data and process of surveillance should undergo periodic
      evaluation and validation. This document is intended to assist professionals who
      plan and conduct surveillance programs as well as those who assure that there is
      appropriate organizational support to accomplish appropriate surveillance. While
      design of surveillance systems must be unique for each organization,
      incorporation of these seven core Recommended Practices for Surveillance provides
      a scientific framework to approach surveillance programs.

PMID- 9638293
TI  - The microbiology "unknown" misadventure.
AB  - A 19-year-old nursing student was hospitalized after several days of nausea,
      vomiting, diarrhea, and fevers. Salmonella paratyphi A was isolated from multiple
      blood cultures. Because this is an unlikely isolate in the United States, an
      investigation ensued. Two and a half weeks earlier, the student had been working
      on a microbiology laboratory exercise "unknown." Both the "unknown" organism and
      the patient's blood culture isolates were identified as S. paratyphi A, with the
      same biochemical reactions and antimicrobial susceptibility results. The
      patient's condition improved with antibiotic therapy, and she was discharged
      after 9 days in the hospital. Conclusions related to our investigation are as
      follows: (1) relatively virulent organisms were unnecessary to fulfill the
      laboratory objectives, (2) pipetting by mouth must never be allowed, (3) proper
      labeling of specimens is imperative, (4) instructors should have knowledge of
      laboratory safety regulations, and (5) it is the obligation of laboratory
      directors and administrators to provide a safe academic environment.

PMID- 9638294
TI  - Infection surveillance in home care: device-related incidence rates.
AB  - BACKGROUND: Four home health agencies of different sizes, including a rural
      agency with many branch offices, participated in a surveillance study. METHODS:
      These agencies used the same definitions for symptomatic urinary tract infections
      in patients with urinary catheters and for bloodstream infections in patients
      receiving intravenous therapy. Identical data and methods were used for
      calculating infection rates, with device-days consistently used as the
      denominator. Each agency's primary goal was to develop baseline information about
      its own infection rates and to use these statistics to detect problems and
      trends. Chart audits were performed if trends or problems were identified. A
      secondary goal was to compare or benchmark infection rates, because there is
      almost no published information in this area of home care. RESULTS: We found that
      our mean infection rates for symptomatic urinary tract infection among patients
      with urinary catheters and for bloodstream infection among patients receiving
      intravenous therapy were similar among the four agencies. The mean rates for all
      four agencies were 4.5 symptomatic urinary tract infections/1000 device-days and
      1.1 bloodstream infections/1000 device-days. CONCLUSION: The methods used here
      can be implemented in other home care agencies. Using the same definitions,
      collecting data for the same type of infections, and using the same rate
      calculations make infection control benchmarking possible between home health
      agencies.

PMID- 9638295
TI  - Infections in solid organ transplantation.

PMID- 9638296
TI  - Testing and evaluation of surgical gown fabrics: comments and concerns.

PMID- 9638297
TI  - Leukocytoclastic vasculitis after pneumococcal vaccination.

PMID- 9638298
TI  - Benefits of sterile water use in an endoscopic laboratory.

PMID- 9638299
TI  - Increasing hospital employee participation in an influenza vaccine program.

PMID- 9638300
TI  - Varicella-zoster virus: infection, control, and prevention.
AB  - Varicella-zoster virus is a herpes virus that produces a primary infection,
      chickenpox, manifested by a vesicular eruption and is considered one of the
      common childhood infectious diseases. After the initial infection the virus
      becomes latent, then when activated it is manifested as herpes zoster, commonly
      known as shingles. This highly communicable human disease is associated with
      serious morbidity and significant mortality, particularly among the
      immunocompromised. When introduced in the hospital, significant disruptions occur
      and serious sequelae may results. Recently, a live virus varicella vaccine was
      approved by the Food and Drug Administration in the United States. Studies have
      shown the vaccine to be safe and effective. Widespread use of this vaccine may be
      beneficial in reducing the opportunities for varicella-zoster virus introductions
      in health care settings.

PMID- 9638301
TI  - Comparison of native, lyso and hydrogenated soybean phosphatidylcholine as
      phospholipid source in the diet of postlarval Penaeus japonicus bate.
AB  - Native and two modified forms of soybean phosphatidylcholine were used to study
      the nutritional effect of their fatty acids for postlarval Penaeus japonicus.
      Five semipurified and isolipidic diets were formulated using casein as a protein
      source. Three diets contained 1.5% of different types of phosphatidylcholine (95%
      purity), i.e. native soybean phosphatidylcholine, hydrogenated soybean
      phosphatidylcholine and 1-acyl lyso soybean phosphatidylcholine, besides 1% of n
      3 highly unsaturated fatty acid formulated as triglycerides. Two negative control
      diets contained either triglycerides or ethyl esters as a source of n-3 highly
      unsaturated fatty acids without phospholipid. The experiment was conducted during
      two successive phases of 20 d starting from 12-d old postlarvae. Feeding the diet
      containing native soybean phosphatidylcholine resulted in significantly better
      growth and resistance to osmotic shock of P. japonicus postlarvae compared to the
      other diets. The total lipid content of the tissue was significantly increased by
      the supplementation of soybean phosphatidylcholine, whereas no significant
      difference was observed for the shrimp fed the modified phosphatidylcholine
      sources compared to the phosphatidylcholine-free diet at the end of the
      experiment. Shrimp fed the diet containing soybean phosphatidylcholine exhibited
      a higher polar lipid fraction in the whole body total lipid mainly as a result of
      the increased proportion of phosphatidylcholine and to a lesser extent of
      phosphatidylinositol at the expense of free fatty acids, free sterols and sterol
      esters. The content of 20:5n-3, 22:6n-3 and total n-3 highly unsaturated fatty
      acids in the shrimp tissue were higher in shrimp fed the native soybean and
      hydrogenated soybean phosphatidylcholine diets compared to those fed the
      phosphatidylcholine-free and 1-acyl lyso soybean phosphatidylcholine-based diets.
      The fatty acid profile of tissue phosphatidylethanolamine was more influenced by
      the type of dietary phosphatidylcholine than that of tissue phosphatidylcholine.
      In the absence of phospholipids in the diet, triglyceride fish oil and a mixture
      of ethyl ester concentrate and coconut oil with similar n-3 highly unsaturated
      fatty acids content were equivalent sources of n-3 highly unsaturated fatty
      acids. The beneficial effects of dietary phospholipids may be due to a more
      efficient transport and utilization of dietary neutral lipids through a better
      lipid mobilization following absorption in the intestinal mucosa rather than due
      to a better emulsification of neutral lipid in the gut lumen. The functionality
      of phosphatidylcholine in the diet of postlarval P. japonicus requires the
      presence of unsaturated fatty acids and an intact fatty acid moiety.

PMID- 9638302
TI  - The effect of porcine bile acids on methane production by rumen contents in
      vitro.
AB  - Hindgut fermentation differs from rumen fermentation by a lower methane
      production and the presence of reductive acetogenesis. Bile acids which are lost
      into the lower digestive tract may have a promoting effect on reductive
      acetogenesis in the hindgut. In this experiment it was investigated if bile acids
      induce reductive acetogenesis in rumen fermentation in vitro. Rumen contents from
      a fistulated cow were incubated in vitro with ground hay and increasing amounts
      of porcine bile acids or bile acid salts. Bile acids inhibited methane production
      up to 70% of the control incubation. The concomitant increase in propionate
      production compensated for the lower methane production so that the 2H-recoveries
      were in a normal range between 79-92%. Therefore the occurrence of reductive
      acetogenesis could be excluded. It is concluded, that bile acids are a
      controlling factor in caecal methanogenesis.

PMID- 9638303
TI  - Inevitable losses of phosphorus in pigs, estimated from balance data using diets
      deficient in phosphorus.
AB  - Faecal losses of phosphorus (P) were determined in 66 growing pigs weighing
      between 30 and 70 kg on a semi-purified diet containing less than 1.3 g P/kg DM.
      Regression analysis showed that the coefficient of absorption of P from this diet
      was 82.5% and that inevitable faecal P excretion of pigs fed this diet was, on
      average, 5.9 mg/kg BW.d-1 with no statistically significant effect of body weight
      on faecal P excretion within the range of body weight studied. Semi-purified
      diets almost identical in composition were also fed to 5 piglets weighing about
      20 kg and to 4 heavy pigs of about 150 kg BW. Inevitable daily faecal losses of P
      were calculated to be 6.2 mg/kg BW in piglets and 6.8 mg/kg BW in the heavy pigs.
      It is concluded that inevitable faecal losses of P do depend on body weight and
      that the variation faecal P excretion was too great to allow detecting this
      effect within the limited range between 30 and 70 kg BW. Further diets were
      obtained by blending various ingredients into the semi-purified diet. From a
      total of 262 balances measured under the condition of suboptimal P supply it is
      concluded that daily inevitable urinary losses of P depend on body weight and, on
      average, amount to 0.35 mg/kg BW. It is concluded that under the conditions of
      suboptimal P supply the utilisation of digestible P is almost complete.

PMID- 9638304
TI  - [Effect of various sources of phosphorus on the apparent digestibility of crude
      nutrients, growing and slaughtering performance as well as selected parameters of
      metabolism in fattening bulls].
AB  - Two long-term individual feeding experiments (336 and 307 days) were carried out
      with 52 (experiment I; Black and White dairy cattle) and 22 (experiment II;
      Yellow cattle) growing bulls. Rations varied in P-content. In experiment I straw:
      concentrate-mixture (1:2.5) were fed, phosphorus content of rations amounted to
      2, 3 or 4 g/kg DM. In experiment II maize silage was fed ad lib. supplemented
      with 2.4 kg concentrate per animal per day. P-content of rations amounted to 3
      and 4 g/kg DM. Apparent digestibility of rations was determined during
      experiments. Blood samples were taken to analyse selected parameters of
      metabolism. Various P-supply did not significantly influence apparent
      digestibility of organic matter and crude nutrients in both experiments. Bulls
      fed 2 g P/kg DM decreased DMI in experiment I already after 50 days of
      experiment. After 168 experimental days daily weight gain of bulls fed with 2 g
      P/kg DM was 124 or 132 g lower than that of bulls fed with 3 or 4 g P/kg DM
      respectively. P-concentration of inorganic P in serum decreased to < 2 mmol/l,
      bone mineralisation was reduced. There exist no significant differences in feed
      intake, weight gain and metabolic parameters of bulls fed with 3 or 4 g P/kg DM.
      Increase of P-supply from 2 to 3 or 4 g/kg DM compensated partially the lower
      weight gain. Application of 3 or 4 g P/kg DM in experiment II effected daily
      weight gains of > 1200 g and did not significantly influence all investigated
      criterions.

PMID- 9638305
TI  - Effect of different technical treatments of rapeseed on the feed value for
      broilers and laying hens.
AB  - The effect of different technical treatments of rapeseed on its feed value for
      broilers and laying hens was the object of the study. The technical treatments
      comprised different grinding procedures (whole seed, roller mill--coarse and fine
      adjustment, flake mill) resulting in different average particle sizes of the
      ground seed and thermal treatments of flaked seed (hydrothermal treatment,
      micronizer, jet sploder). Each thermal treatment was carried out at two
      temperatures. A marked increase in the digestibility of organic matter and of the
      AMEN content was observed as the average particle size of the seed was decreased
      to < or = 0.56 mm and was much more pronounced for the broilers. AMEN contents of
      21.1 to 22 and 22.6 to 23 MJ/kg DM were observed at this particle sizes for
      broilers and hens, respectively. Thermal treatment of rapeseed improved the
      apparent crude fat digestibility slightly whereas the apparent crude protein
      digestibility tended to decrease especially at the higher temperatures. This
      resulted in inconsistent changes in the apparent digestibility of the organic
      matter and the AMEN content. Only the treatment with hot air (jet sploder) seemed
      to have preferential effects on the feed value for both broilers and hens. For
      the thermal treatments AMEN contents ranged from 18.8 to 21.9 and 19.0 to 24.3
      MJ/Kg DM for broilers and hens, respectively.

PMID- 9638306
TI  - The effect of sealing and of additives on the fermentation characteristics and
      mould and yeast counts in stretch film wrapped big-bale lucerne silage.
AB  - The effect of number of film layers was investigated in silages produced in
      wrapped big bales. The herbage used was difficult to ensile lucerne wilted to DM
      levels of 320-490 g/kg. Fermentation changed to a more homofermentative process
      as the number of film layers increased. An increasing number of film layers (4,
      6, 8 or 10) also resulted in a notable decrease in moulds and yeasts. Four layers
      could not guarantee successful preservation in lucerne, and higher numbers of
      undesirable micro-organisms were detected. Hard stalks damaged the first two film
      layers during wrapping in the bales. Effect of number of film layers was more
      important than effect of additives for inhibition of mould and yeast counts.

PMID- 9638307
TI  - Research note: a comparison of metabolisable energy values of lucerne and barley
      between young and mature ostriches.
AB  - Apparent and true metabolisable energy (ME) values, corrected for zero nitrogen
      retention, of lucerne and barley were compared in balance studies between young
      (six months old, 50 to 60 kg BW) and mature (30 months old, 110 to 120 kg BW)
      ostriches. Birds were housed in individual metabolism crates and excreta
      collection were performed over a five day period after an adaptation period of
      seven days. Apparent metabolisable energy, corrected for zero nitrogen retention,
      (AMEN) of 9.17 +/- 0.251 MJ/kg (lucerne) and 14.24 +/- 0.136 MJ/kg (barley) for
      young ostriches do not differ (P > 0.05) from values of 8.97 +/- 0.226 MJ/kg
      (lucerne) and 14.21 +/- 0.134 MJ/kg (barley) obtained for mature ostriches. Also
      no significant differences occurred between true metabolisable energy, corrected
      for zero nitrogen retention, (TMEN) values of 9.16 +/- 0.450 MJ/kg (lucerne) and
      13.94 +/- 0.390 MJ/kg (barley) for young ostriches and 9.26 +/- 0.412 MJ/kg
      (lucerne) and 13.92 +/- 0.316 MJ/kg (barley) for mature ostriches. It is
      concluded that similar AMEN and TMEN values of feedstuffs would be suitable in
      ostrich diet formulation for age groups older than six months.

PMID- 9638308
TI  - Metabolism of 2(R,S)-1,2-bis(nicotinamido)propane, a new agent with anti
      vasospasm activity, in rats and rabbits.
AB  - 1. The metabolic fate of the new Anti-vasospasm Substance (AVS), 2(R,S)-1,2
      bis(nicotinamido)propane (CAS 79455-30-4), was studied using 14C-labelled drug in
      rats and rabbits by thinlayer chromatography, mass spectrometry and nuclear
      magnetic resonance. 2. More than 75% of the radioactivity was observed in the
      urine when 14C-AVS was given intravenously to rabbits and rats, showing that the
      major route of excretion of AVS and its metabolites is via the kidney. 3. Marked
      species differences were observed in the metabolism of AVS in rats and rabbits.
      In rabbits, the major metabolites were 6- or 6'-monopyridone (23.5% of dose), and
      there were a few minor metabolites such as the mono N- or N1-oxide of two
      pyridine rings. In rats, however, only approximately 5% of the radioactivity was
      due to metabolites, mainly the N-oxide. 4. Formation of AVS monopyridone by
      rabbit liver cytosol was much higher than in rats, and was markedly inhibited by
      the aldehyde oxidase inhibitor, menadione. The difference between rats and
      rabbits in oxidase activity giving the AVS monopyridone metabolite correlated
      well with that measured by the general assay method for aldehyde oxidase. These
      results suggest that the species difference in AVS metabolism between rats and
      rabbits is mainly due to the difference in aldehyde oxidase activity, which is
      involved in formation of the monopyridone.

PMID- 9638309
TI  - Pharmacokinetics of tramadol and bioavailability of enteral tramadol
      formulations. 2nd communication: drops with ethanol.
AB  - The pharmacokinetics and the absolute bioavailability of tramadol hydrochloride
      (CAS 36282-47-0) after oral administration of Tramal drops (with ethanol) were
      determined in a balanced cross-over study in 8 (4 male and 4 female) volunteers
      in comparison with the intravenous injection. Each fasting volunteer received two
      single doses of 100 mg tramadol-HCl, one by oral (1 ml of drops) and one by
      intravenous route (2 ml of a solution for injection). The formulations were
      administered in the morning; the washout period was one week. Serum and urine
      concentrations of tramadol-HCl were determined by gas chromatography-mass
      spectrometry and gas chromatography, respectively, and the pharmacokinetic
      evaluation was carried out model-dependently. Only the extent of bioavailability
      and the renal clearance were calculated model-independently. The extent of the
      absolute bioavailability (F) of tramadol after oral administration of the drops,
      based on AUC data, was 66.3% (point estimate; n = 8) with a 95% confidence
      interval of 58.1-75.6% (ANOVAlog). The areas under the serum concentration curves
      of tramadol-HCl calculated by curve fitting (AUC), which agreed very well with
      the model-independently determined areas (AUC), were 2390 +/- 712 h.ng/ml (p.o.)
      and 3490 +/- 510 h.ng/ml (i.v.) (mean +/- SD; n = 8). After oral administration
      the means of the serum concentration peaks were 308 +/- 89 ng/ml (cmax) and 1.20
      +/- 0.39 h (tmax), the half-life of absorption was 0.34 +/- 0.18 h (t1/2,ka) and
      the lag time 0.23 +/- 0.01 h (t0). The biological half-life in the terminal phase
      (t1/2,beta) was 5.5 +/- 0.9 h and agreed well with the value of 5.2 +/- 0.8 h
      determined after i.v. injection. There were large differences between the
      volunteers in the distribution rate. For the slower distribution half-life
      (t1/2,alpha) mean values of 1.2 +/- 0.7 h (p.o.; n = 6) and 1.9 +/- 0.7 h (i.v.;
      n = 6) were obtained. The values determined after i.v. injection for the total
      distribution volume and the total and renal clearance were 216 +/- 21 l
      (Vd,beta), 487 +/- 71 ml/min (Cltot) and 77 +/- 20 ml/min (Clren), respectively.
      These results show that after administration of the drops (with ethanol) the
      active ingredient tramadol is rapidly absorbed and that the extent of the
      absolute bioavailability is about the same as after oral administration of
      tramadol capsules.

PMID- 9638310
TI  - Disposition of the novel anti-schizophrenic drug [14C]olanzapine in male Fischer
      344 and female CD rats following single oral dose administration.
AB  - These studies comprehensively evaluate the distribution of [14C]olanzapine (2
      methyl-4-(4-methyl-1-piperazinyl)-10H-thieno(2,3-b)-1,5)benzodiazepin e, CAS
      132539-06-1, LY170053) a novel anti-schizophrenic compound, following single oral
      dose administration in male Fischer 344 rats, and pregnant and non-pregnant
      lactating female CD rats. The disposition of radiocarbon was determined and
      tissue pharmacokinetics evaluated in male Fischer 344 rats following a single
      oral 8 mg/kg dose at 2, 6, 24, 48, 72, and 96 h postdose using quantitative whole
      body autoradiographic (QWBA) techniques in conjunction with image analysis. This
      study demonstrated that [14C]olanzapine and/or metabolites were rapidly absorbed
      and widely distributed with a tmax of 2 h postdose in most tissues. Persistent
      but declining concentrations of radiocarbon were detected in feces, kidney,
      liver, and Harderian, preputial, and thyroid glands at 96 h postdose. Placental
      transfer of [14C]olanzapine was evaluated at 0.5, 1, 3, 6, and 24 h postdose on
      gestation day 12, the mid-point of organogenesis, by tissue dissection and liquid
      scintillation spectroscopy (LSC) and on gestation day 18, a time which enabled
      visualization of fetal tissues by whole-body autoradiography (WBA). The placental
      transfer studies indicated that all tissues analyzed had a tmax of 1 or 3 h
      postdose with maternal liver consistently containing high concentrations of
      radiocarbon. Embryos contained measurable concentrations of radiocarbon
      throughout the time course of these studies confirming that [14C]olanzapine
      and/or its metabolites crossed the placenta. Additionally, the disposition of
      [14C]olanzapine in milk and plasma of lactating female CD rats confirmed pup
      exposure through milk ingestion.

PMID- 9638311
TI  - Absorption of the new anxiolytic compound deramciclane in rats, dogs and rabbits.
AB  - The absorption of deramciclane fumarate ((1R,2S,4R)-(-)-N,N-dimethyl-2-[(1,7,7
      trimethyl-2-phenylbicyclo [2,2,1] hept-2-yl) oxy] ethane amine-2-(E)-butenedioate
      (1:1), CAS 120444-78-8, EGIS-3886), a new anxiolytic compound, was studied in
      rats, dogs and rabbits by using 3H-camphor- or 14C-phenyl-labelled radioisomers
      of the substance. The compound was readily absorbed from the intestinal tract
      after oral administration. The absorption of 14C-deramciclane was also studied
      from the isolated intestinal loops of rats (duodenal, jejunal, ileal loops) and
      dogs (duodenal loop). The absorption was faster in rats and rabbits than in dogs
      (tmax = 1 h or 6 h, respectively). The radioactivity was not absorbed from the
      isolated stomach of any species studied for 2 h. Meanwhile, the substance was not
      decomposed by the gastric juice, as it has been proved by TLC and MS analyses.
      Deramciclane is preferentially excreted via the bile. The intensity of its bile
      excretion is higher in rats than in dogs. Higher plasma levels of labelled
      deramciclane were found in female than in male rats.

PMID- 9638312
TI  - Comparative autoradiographic investigations on the tissue distribution of
      benfotiamine versus thiamine in mice.
AB  - The tissue distribution of two therapeutically applied preparations of B-vitamins
      were investigated in blood and selected organs (liver, brain, muscle, kidney) of
      laboratory mice using autoradiographic techniques. Incorporation of lipid-soluble
      3H-benfotiamine (CAS 22457-89-2) and water-soluble 3H-thiaminehydrochloride (CAS
      67-03-8) (200 microCi, equivalent to 105 mg vitamin/kg body weight) was monitored
      between 0.75 and 168 h after an oral or subcutaneous administration. The labelled
      tissue slices were autoradiographically analysed after a differential
      histochemical extraction procedure to evaluate the respective total
      radioactivity, the uptake into lipid-soluble, water-soluble and residual
      macromolecular compounds. Evaluation of these autoradiographic data (given as
      mumol vitamin preparation/mg tissue equivalent) proved that benfotiamine is
      incorporated much better than thiaminehydrochloride independent of the
      administration mode. In muscle and brain tissue a 5 to 25 fold higher amount of
      tracer incorporation was registered following benfotiamine as compared with the
      thiamine application, whereas in all other organs the difference in the label was
      mostly between 10 and 40%. Concerning the organ specific distribution, liver and
      kidney were the structures labelled highest by both substances and administration
      procedures. In the liver, concerning all incorporation times, a higher proportion
      of residual macromolecular compounds was found, whereas in the kidney the
      proportions of lipid- as well as of water-soluble materials prevailed. These data
      should be clinically relevant.

PMID- 9638313
TI  - Efficacy and safety of glucosamine sulfate versus ibuprofen in patients with knee
      osteoarthritis.
AB  - A double-blind therapeutic investigation was performed on 178 Chinese patients
      suffering from osteoarthritis of the knee randomized into two groups, one treated
      for 4 weeks with glucosamine sulfate (GS, CAS 29031-19-4, Viartril-S) at the
      daily dose of 1,500 mg and the other with ibuprofen (IBU, CAS 15687-27-1) at the
      daily dose of 1,200 mg. Knee pain at rest, at movement and at pressure, knee
      swelling, improvement and therapeutic utility as well as adverse events and drop
      outs were recorded after 2 and 4 weeks of treatment. The variables were recorded
      also after 2 weeks of treatment discontinuation in order to appreciate the
      remnant therapeutic effect. Both GS and IBU significantly reduced the symptoms of
      osteoarthritis with the trend of GS to be more effective. After 2 weeks of drug
      discontinuation there was a remnant therapeutic effect in both groups, with the
      trend to be more pronounced in the GS group. GS was significantly better
      tolerated than IBU, as shown by the adverse drug reactions (6% in the patients of
      the GS group and 16% in the IBU group--p = 0.02) and by the drug-related drop
      outs (0% of the patients in the GS group and 10% in the IBU group--p = 0.0017).
      The better tolerability of GS is explained by its mode of action, because GS
      specifically curbs the pathogenic mechanisms of osteoarthritis and does not
      inhibit the cyclo-oxygenases as the non-steroidal anti-inflammatory drugs
      (NSAIDs) do, with the consequent anti-inflammatory analgesic activities but also
      with the several adverse reactions due to this not targeted effect. The present
      study confirms that GS is a selective drug for osteoarthritis, as effective on
      the symptoms of the disease as NSAIDs but significantly better tolerated. For
      these properties GS seems particularly indicated in the long-term treatments
      needed in osteoarthritis.

PMID- 9638314
TI  - Synergistic effects of ularitide acetate with classical bronchorelaxants on
      guinea-pig tracheal smooth muscle.
AB  - Ularitide (CAS 118812-69-4, urodilatin) is a member of the family of the atrial
      natriuretic peptides. In the present study, the relaxant effects of ularitide
      acetate, isoproterenol (isoprenaline) hemisulfate, aminophylline, zaprinast, and
      different combinations between these drugs were investigated on methacholine
      chloride-precontracted guinea-pig tracheal smooth muscle. Ularitide acetate was a
      weaker bronchorelaxant than isoproterenol hemisulfate and aminophylline. Moreover
      the relaxation induced by ularitide acetate was reversible, while the relaxation
      induced by isoproterenol hemisulfate, aminophylline, and zaprinast was
      irreversible. Combinations between in each case two of these substances were
      overadditive, if the phosphodiesterase-inhibiting component was applicated before
      the combination partner. Their effects were only additive, if the combination
      partners were applicated simultaneously. All combinations between ularitide
      acetate and isoproterenol hemisulfate, aminophylline, or zaprinast respectively
      relaxed the tracheas irreversibly. These results suggest that ularitide acetate
      might be a novel partner for classical bronchorelaxants in potent bronchorelaxing
      combinations in the therapy of asthma bronchiale.

PMID- 9638315
TI  - [The action of the proton pump inhibitor pantoprazol against acetylsalicylic acid
      induced gastroduodenopathy in comparison to ranitidine. An endoscopic controlled,
      double blind comparison].
AB  - In a randomised double-blind parallel study the gastroduodenal tolerability of
      300 mg acetylsalicilic acid daily (ASA, CAS 50-78-2) has been evaluated in the
      presence of placebo (n = 8), 40 mg pantoprazole (CAS 102625-70-7) daily (8 a.m.)
      (n = 16) and 300 mg ranitidine (CAS 66357-35-5) daily (8 a.m.) (n = 16) in
      healthy volunteers using upper GI-endoscopy. The treatment period lasted 14 days,
      endoscopic controls were performed at entry and repeated at day 14. At entry, the
      mean endoscopic score averaged 1.0 +/- 0.0 (+/- SEM) in the ASA/placebo, in the
      ASA/pantoprazole and the ASA/ranitidine group. In the placebo experiments 300 mg
      ASA daily induced marked gastroduodenal lesions at day 14 (lesion score of 6.8 +/
      1.4 (+/- SEM). Concomitant administration of 40 mg pantoprazole daily offered
      significant protection against 300 mg ASS daily on day 14 (2.1 +/- 0.6) (+/- SEM)
      (p < 0.05) vs ASA/placebo. 300 mg ASA plus 300 mg ranitidine daily reduced the
      damaging score to 4.9 +/- 1.2 (+/- SEM) (n.s. vs ASA/ placebo). Our data suggest
      that coadministration of 40 mg pantoprazole daily reduces significantly
      gastroduodenal lesions evoked by 300 mg ASA daily.

PMID- 9638316
TI  - [Intravesical instillation of trospium chloride, oxybutynin and verapamil for
      relaxation of the bladder detrusor muscle. A placebo controlled, randomized
      clinical test].
AB  - Therapy of detrusor hyperactivity with anticholinergic agents often is followed
      by adverse drug reactions. Intravesical application may be an interesting
      alternative. A randomised, single-blind, placebo-controlled, mono-centre clinical
      trial was carried out in 84 patients with urgency or urge incontinence. Due to
      intravesical administration of oxybutynin (CAS 5633-20-5) (n = 21) and trospium
      chloride (CAS 10405-02-4) (n = 21), respectively, a significant increase in
      maximum bladder capacity and decrease of detrusor pressure accompanied by an
      increase of residual urine were found in comparison to placebo in urodynamical
      investigations. Improvement of uninhibited bladder contractions occurred leading
      to higher filling volume. Under verapamil (CAS 152-11-4) (n = 21) no marked
      changes in the efficacy variables were found compared with placebo. All patients
      completed the study and were assessed with regard to efficacy and safety. No
      adverse events or marked changes in the vital signs were reported. The immediate
      onset of effect and the lack of adverse drug reactions suggest that treatment
      with topical oxybutynin or trospium chloride is an effective alternative in
      patients with intolerable side effects when orally treated. In addition,
      intravesical administration may be indicated in patients with bladder spasms due
      to indwelling catheter or in order to increase bladder capacity before
      percutaneous cystostomy.

PMID- 9638317
TI  - In vitro studies on the influence of carbomers on the availability and
      acceptability of estradiol gels.
AB  - The objective of the present study was to evaluate the pharmaceutical properties
      of estradiol (CAS 50-28-2) gels: pH, viscosity, texture, spreadability,
      evaporation of solvent and transcutaneous diffusion from carbomer-based
      formulations. This study was performed with the aim of measuring possible
      pharmaceutical differences as a function of the nature of the polymers used. The
      results obtained show a similarity of behaviour for the Estreva gels made with
      carbomers Carbopol 1342 (C 1342) and 1382 (C 1382). The reference gel,
      commercially available in France and made with the carbomer Carbopol 934 (C 934)
      is different in terms of its rheological criteria.

PMID- 9638318
TI  - Effects of a standardized mistletoe preparation on metastatic B16 melanoma
      colonization in murine lungs.
AB  - The immune response-modifying drug Lektinol is a mistletoe preparation which is
      standardized with respect to bioactive viscum album agglutinin, the most active
      component of mistletoe. The present study was designed to evaluate the
      antimetastatic effects of this preparation following intravenous injection of B16
      melanoma cells into mice. The standardized mistletoe extract was administered
      intravenously in doses of 100, 1000 or 5000 microliters/kg (equivalent to 3, 30
      or 150 ng/kg of viscum album agglutinin) once daily for three weeks. An
      inhibition of mean pulmonary metastatic colonization of 58 to 95%, as measured by
      the number of melanoma cells on lung tissue slides, and a significant decrease of
      percentage of bronchoalveolar lavage pigmented cells were observed. In addition,
      a correlation of this antimetastatic activity with cellular immune parameters was
      investigated. In lavage fluids from the tumor-bearing mice, there was a 5 to 6
      fold significant increase in the percentage of MAC-1+ (CD11b/CD18)
      immunocompetent macrophages in comparison with cells from vehicle-treated
      animals. The percentages of double-positive immature CD4+8+ thymocytes were
      significantly increased in animals treated with the standardized mistletoe
      extract. There were no signs of treatment-related toxicity. The results of this
      study indicate that the standardized mistletoe extract shows antimetastatic
      activity against B16 melanoma lung colonization.

PMID- 9638319
TI  - [Quality control and documentation of effectiveness of bacterial autovaccines
      with the use of flow cytometry].
AB  - Autovaccines are bacterial preparations derived from non pathogenic autologous
      bacteria of human origin. In the course of microbiological therapy these
      individual bacterial vaccines are mainly used in conditions of chronic
      inflammatory disorders of the respiratory or gastrointestinal tract as well as
      allergic diseases. Being autologous bacterial preparations from the patients own
      flora the control of batch variabilities of these individual products represents
      a special challenge for the manufacturer. A flow cytometric method suitable for
      batch control of autovaccines is described. The method is based upon the
      determination of the de novo expression of the CD69 antigen on different
      leucocyte subpopulations in whole blood cultures after preincubation of cells
      with different batches of autovaccines. Thus, manufacturers of autovaccines and
      other microbial preparations are able to reliably control batch variability and
      immunological activity of such products in accordance with drug regulations. The
      results of this study highlight the pharmaceutical quality of the individual
      therapeutic agent autovaccine.

PMID- 9638320
TI  - Absorption and excretion of radioactivity after intravaginal administration of an
      advanced delivery system of 14C-flutrimazole vaginal cream to postmenopausal
      women.
AB  - In order to improve the effectiveness of treatment of vaginal yeast infections,
      flutrimazole, (CAS 119006-77-8), a broad spectrum local imidazolic fungicide, has
      been formulated in an advanced delivery system (Site Release, here in after
      briefly referred to as SR) designed to improve vaginal retention of the drug. To
      determine the extent of absorption of 14C-flutrimazole from this formulation, the
      absorption and excretion of total radioactivity have been studied in healthy
      postmenopausal female volunteers after intravaginal administration of
      approximately 5 g of SR Vaginal Cream containing 2% 14C-flutrimazole.
      Concentrations of unchanged flutrimazole have also been measured in plasma and
      urine, using a validated gas chromatography-mass spectrometry method. The rate of
      absorption was slow, with a mean peak plasma radioactivity concentration, Cmax,
      of 56 ng equivalents/ml, achieved at a mean Tmax of 28 h. Corresponding
      parameters for flutrimazole were 1.94 ng/ml at 24 h. At 24 h post-dose, unchanged
      flutrimazole represented only 3% of plasma total radioactivity which indicates
      that flutrimazole is extensively metabolised in man. Total radioactivity and
      unchanged flutrimazole were eliminated from plasma with terminal half-lives of 37
      and 22 h, respectively. From the proportion of the radioactive dose excreted in
      urine and faeces, the maximal extent of absorption indicated for the intravaginal
      dose was about 8%, which is similar to that observed with other imidazolic
      compounds administered by this route. Thus, the formulation achieves the aim of
      prolonged drug action through the maintenance of therapeutic concentrations of
      the drug at the site of infection without notably increased absorption.

PMID- 9638321
TI  - Identification and development of new biopharmaceuticals.
AB  - The 34 protein based biopharmaceuticals which are presently on the market reached
      a total sale of 10 Mio $ in 1996. Out of 500 biopharmaceutical under
      investigation, 200 are already in clinical trial programs. Although
      biopharmaceuticals have good records in efficacy and drug safety, biologics are
      still competitive due to economic reasons. In future in some cases gene therapy
      or oligonucleotide antisense therapy as modern technologies for in vivo protein
      synthesis regulation will be an alternative to protein replacement therapy. All
      three therapeutic approaches will be supported by the human genome project which
      will give new hints on genetic disorders related to specific diseases. The
      identification of new therapeutic developments will be on the DNA-, RNA- and
      protein level. The decision whether the therapeutic principle will be gene
      therapy or whether the differential genomic analysis will provide just a research
      tool for high through-put screening of small molecules will be decided upon the
      evaluation of the results of the genomic projects and the research strategy of
      the company.

PMID- 9638322
TI  - Recovery and rehabilitation following subarachnoid haemorrhage. Part I: Outcome
      after inpatient rehabilitation.
AB  - BACKGROUND AND PURPOSE: Although subarachnoid haemorrhage (SAH) is a subtype of
      stroke, functional outcome following rehabilitation for SAH must be considered
      distinct from that of cerebral infarction because of the younger age and the
      difference in pathology and resultant neurologic deficits. The purposes of this
      study were to: (1) describe the demographic and clinical characteristics of SAH
      patients receiving rehabilitation; (2) describe functional outcomes following
      inpatient rehabilitation; and (3) investigate possible relationships between
      patient characteristics and functional outcomes. METHODS: Retrospective chart
      review of SAH patients admitted to inpatient rehabilitation. Functional Outcomes
      rated by the Functional Independence Measures (FIM). Analysis with descriptive
      and nonparametric statistics. RESULTS: Eighty patients with SAH admitted to a
      rehabilitation unit with a mean age of 54 years. Fifty-seven had identified
      aneurysms as a cause of SAH. Seventy-four subjects (93%) presented with Hunt and
      Hess grades of 3-5. The median length of stay was 26 days in acute care and 49
      days in rehabilitation. Seventy patients (88%) were discharged home. The mean
      admission FIM was 59.5 and mean discharge FIM 91.0. The FIM efficiency (aggregate
      change in FIM/day) was 0.62/day and the average rate of FIM gain 0.97 points/day.
      Hydrocephalus negatively influenced outcome (p = 0.05). There was a trend for
      subjects with worse Hunt and Hess scores at onset to have poorer discharge FIM
      scores. CONCLUSION: SAH patients receiving inpatient rehabilitation make
      functional gains, although the rate of gain is less than for TBI or stroke. These
      SAH patients represent a subgroup with more severe SAH at onset than the total
      population of SAH survivors. The presence of hydrocephalus negatively impacts on
      outcome. Further detailed study of functional and neuropsychological outcome in
      SAH survivors is needed.

PMID- 9638323
TI  - Incidence and outcomes of traumatic brain injury and substance abuse in a New
      Zealand prison population.
AB  - The present study investigated the rates and perceived effects of past traumatic
      brain injury (TBI) and substance use in a prison population. Responses to a
      questionnaire indicated that 86.4% of the 118 respondents had sustained a TBI,
      with 56.7% reporting more than one, and rates of illicit substance use were
      higher than the general population. Maori reported 12% more TBI and more
      substance use than non-Maori. All those with TBI reported difficulties with
      general memory and socialization on a problem rating scale, but there was no
      relationship between level of difficulty and severity of TBI, problems with
      interpersonal relationships, family, and finances were associated with greater
      substance use.

PMID- 9638324
TI  - Caring for a family member with a traumatic brain injury.
AB  - The responses to a questionnaire on subjective burden are reported for 52 primary
      caregivers of a group of persons with traumatic brain injuries sustained an
      average of 6 years previously. The aim of the study was to examine satisfaction
      with social support, perception of coping skills, and appraisal of symptoms as
      predictors of strain in the carers. A range of responses, both positive and
      negative, to the work of caring for a relative with a head injury was reported. A
      high prevalence rate of emotional and behavioural changes in the persons with
      head injuries was found and the amount of distress caused by these symptoms was
      found to be predictive of burden. The other factor important in predicting burden
      was the carers' ratings of their satisfaction with their ability to cope with the
      work of caregiving. Social support, injury severity, and the demographic
      characteristics of the persons with head injury and their carers were not
      significant predictors. Depression in the carers was also investigated and the
      variable most predictive of elevated depression scores was coping satisfaction.
      These findings reinforce the importance of strengthening carers coping resources
      in rehabilitation work with head injured persons and their families.

PMID- 9638325
TI  - Primary caregivers of persons with brain injury: life change 1 year after injury.
AB  - The impact of a traumatic brain injury on the family of the injured person is
      just beginning to be explored. In the current study, 61 primary caregivers were
      contacted at 1 year following injury. They completed the Relative and Friend
      Support Index, Social Support Index, Trauma Complaints List and the Life Change
      Question. The majority of caregivers indicated at least mild negative life change
      following the brain injury. Greater social support was correlated with less life
      change and greater injury severity was correlated with negative life change.
      Neither of these relationships was found to be significant at the 0.05 level. A
      significant positive correlation was found between caregivers' perception of
      deficits and the degree of negative life change. Perceived deficits accounted for
      the greatest amount of variance in life change followed by relative and friend
      support when all variables were entered into a stepwise regression. Further
      analyses indicated that the most significant factor of the Trauma Complaints List
      in predicting life change may be problems with cognition, which accounted for a
      significant amount of the variance in life change. Implications for counselling
      and further research regarding caregivers of persons with brain injury are
      discussed.

PMID- 9638326
TI  - The ability to effect intended stress following traumatic brain injury.
AB  - This study was designed to explore the production of word stress following
      traumatic brain injury (TBI). Ten subjects with TBI and ten matched normal
      controls produced a sentence with stress elicited on different words. The
      difference between stressed and unstressed productions of the same word was
      calculated for intensity, fundamental frequency and duration. Subject's intensity
      range, fundamental frequency range and vital capacity were also obtained. Naive
      listeners judged which word was stressed within each sentence. Individuals with
      TBI were significantly less accurate conveying intended stress compared with
      normal controls. Individuals with TBI produced significantly less difference in
      duration between stressed and unstressed words. There was no correlation for
      either group between percentage change in intensity, fundamental frequency, or
      duration and the related physiological range. Durational control requires subtle
      physiological adjustments that individuals with TBI may be unable to accomplish.
      Further, compensatory strategies may place excessive cognitive demands on the
      speaker. Thus, the production of stress contrasts may not be amenable to
      therapeutic intervention. Rather, listeners may be required to rely on context to
      infer intended stress.

PMID- 9638327
TI  - Are the subjective complaints of traumatically brain injured patients reliable?
AB  - The present study was designed to compare the subjective complaints of 50
      traumatically brain injured (TBI) patients with the observations of their
      significant others. The complaints of the TBI patients and their significant
      others were contrasted according to the severity of the TBI and the type of
      complaint (physical, cognitive/behavioural and emotional). While no differences
      were found in physical complaints, the cognitive/behavioural and emotional
      complaints of TBI patients, regardless of the severity of the initial TBI, were
      significantly under-reported in comparison to the observations of their
      significant others. The data suggests that while this finding was most likely due
      to the TBI patients' poor awareness, it was unlikely to be the result of
      psychological denial since all of these individuals were evaluated in the context
      of being a plaintiff in personal injury litigation or a claimant in a Workers'
      Compensation claim. The data suggests that the cerebral trauma these patients
      sustained played a major role in their ability to recognize their cognitive,
      behavioural and emotional symptoms. Finally, the data suggests that clinicians
      should obtain information about the TBI patients' cognitive/behavioural and
      emotional functioning from their significant others, rather than rely entirely on
      the TBI patients' subjective assessment of these problems.

PMID- 9638328
TI  - Assessment of neuroendocrine dysfunction following traumatic brain injury.
AB  - Posttraumatic neuroendocrine pathology may be a clinically significant
      complication following traumatic brain injury (TBI). Metabolic abnormalities are
      described after TBI in two cases. A 21 year old male injured in a motor vehicle
      accident admitted in a minimally responsive condition presented with fluctuating
      high sodium levels, undetectable serum testosterone, and depressed cortisol and
      thyroid function. Imaging revealed near complete avulsion of the pituitary stalk
      leading to panhypopituitarism. A 38 year old male admitted for occipital skull
      fractures and brain contusions presented with hyponatremia and low serum
      testosterone. Both patients required hormonal replacement and correction of
      electrolyte abnormalities. A screening protocol adapted for selected patients at
      risk for endocrine problems is described. While neuroendocrine screening is not
      advocated in all TBI patients, physicians should be aware of the importance of
      neuroendocrine dysfunction following TBI.

PMID- 9638329
TI  - Increase in the chronically monitored cerebrospinal fluid pressure after
      experimental brain injury in rats.
AB  - The early effects of experimental brain injury with diffuse axonal lesions on
      intracranial pressure (i.c.p.), mean arterial pressure (MAP) and cerebral
      perfusion pressure (CPP) in rats have been already studied. The aim of this
      experiment was to examine the effects of brain injury on ICP, MAP and CPP during
      the first few days post-injury. In order to do that, an accurate technique of ICP
      measurement had to be developed. In a series of eight rats, a translumbar
      intrathecal catheter (TIC) was surgically introduced allowing repeated
      measurements of cerebrospinal fluid pressure (CSFP). Under anaesthesia, a second
      series of nine rats were equipped simultaneously with TIC and an intracranial
      fiberoptic device to measure ICP. Simultaneous measurements of CSFP and ICP were
      recorded for baseline values, than during and after jugular compression which was
      intended to induce an acute and significant increase in ICP. A third series of 53
      rats having TIC received an experimental severe brain injury. MAP was measured
      non-invasively and CPP was calculated as CPP-MAP. CSFP, MAP and CPP were
      intermittently measured during 5-6 post-traumatic days and compared to the values
      obtained during ten control rats (SHAM). A clinical score was used to compare
      clinical condition. The results showed that the translumbar CSFP accurately
      measured ICP in rats having normal or acutely increased ICP. The experimental
      brain injury induced increased CSFP lasting up to 5-6 days, with increased MAP
      during the first 6 hours. CPP values were compromised at 24-48 hours. The
      clinical performance was reduced in the brain-injured rats. The translumbar
      technique of CSFP measurement reflected exact ICP in normal and acutely increased
      ICP in rats. Experimental brain injury with diffuse axonal lesions can increase
      lumbar CSFP in rats for many days.

PMID- 9638330
TI  - Adhesion and cytosolic dye transfer between macrophages and intestinal epithelial
      cells.
AB  - Activated macrophages (M phi) found in the intestinal lesions of patients with
      inflammatory bowel disease (IBD) secrete many inflammatory mediators which can
      regulate intestinal epithelial cell (IEC) function. However, little is known
      about direct M phi-IEC interactions. Two potential mechanisms by which cells may
      interact are through specific receptor-ligand binding of adhesion molecules, such
      as integrins or cadherins, and by exchange of cytoplasmic substances through
      transmembraneous channels called gap junctions. We investigated whether M phi
      could adhere to epithelial cells in culture and form transmembrane communication
      channels as defined by dye transfer. Primary cultures of murine M phi and a M phi
      cell line, P388D1, adhered to Mode-K and IEC6, but not CMT-93 IEC. Antibody
      blocking studies determined that P388D1-Mode-K binding was partially dependent on
      beta 2 integrin (CD18) function, Mode-K constitutively expressed CD106 (VCAM-1)
      and cell associated fibronectin, while P388D1 expressed low levels of CD49d/CD29
      (VLA4) but blocking antibodies to these surface molecules did not inhibit P388D1
      Mode-K adherence. Transfer of calcein dye from M phi to IEC was quantitated by
      flow cytometry and was dependent on M phi-IEC adhesion. Dye transfer was
      concentration dependent in that the fluorescence intensity of Mode-K was
      proportional to the number of adherent P388D1 cells as well as the dye load of
      the M phi. These results indicate that M phi interact with IEC by adhesion and
      possibly through gap junctions and may thus regulate IEC function by direct cell
      cell communication.

PMID- 9638331
TI  - The apical lamina and its role in cell adhesion in sea urchin embryos.
AB  - The hyaline layer (HL) is an extracellular matrix surrounding sea urchin embryos
      which has been implicated in a cell adhesion and morphogenesis. The apical lamina
      (AL) is a fibrous meshwork that remains after removal of hyalin from the HL and
      the fibropellins (FP) are glycoproteins thought to be the principal components of
      the AL. Using anti-FP antibodies (AL-1 and AL-2) we report immunoprecipitations
      and affinity purifications yield a high molecular weight complex comprised of the
      FP glycoproteins. The three components form a complex, stabilized by disulphide
      cross-linking and have stochiometric ratios of 2 FPIa molecules to 1 each of FPIb
      and FPIII. Pulse chase experiments indicate all 3 FP's are synthesized throughout
      development with peaks in synthesis during cleavage and a sustained peak
      beginning at hatching. Using immunogold and immunoperoxidase localization, the FP
      localize to a fibrillar complex forming the innermost layer of the HL. In cell
      adhesion experiments, cells adhere to affinity purified FP in a temperature, time
      and concentration dependent manner. Cell adhesion to Fp is about 70% of that seen
      when hyalin is used as a substrate. Pretreating with AL-1 and AL-2 reduces in
      vitro cell adhesion by about 65%. We conclude FP's form a fibrillar complex,
      which is synthesized throughout early development and functions, with other
      components of the HL, as a substrate for cell adhesion.

PMID- 9638332
TI  - Down-regulation of laminin-binding integrins by 1 alpha,25-dihydroxyvitamin D3 in
      human melanoma cells in vitro.
AB  - In the present investigation the effect of 1 alpha,25(OH)2D3 on the expression of
      the integrin laminin receptor on the melanoma cell line SK-MEL-28 has been
      examined. The SK-MEL-28 cells were shown to contain high-affinity receptors for 1
      alpha,25(OH)2D3 and cell proliferation was found to be inhibited in a dose
      dependent manner in response to the hormone. Using monoclonal antibodies against
      the alpha 6-sub-unit of the integrin laminin receptor, immunocytochemistry
      demonstrated that exposure of cells to 1 alpha,25(OH)2D3 for 5 days caused a
      reduced staining intensity. This observation was further confirmed by dot blot
      analysis, where a dose-dependent decline of alpha 6 expression was obtained after
      treatment of the cells with 1 alpha,25(OH)2D3 for 6 days. FACS-analysis was
      performed in order to quantify this decline, and it was found that the level of
      alpha 6-subunits on the cell surface was reduced by more than 40%. Additional
      investigations including Northern blot analyses of poly(A)+RNA extracts also
      showed a dose-dependent reduction of alpha 6 mRNA. Interestingly, the decrease of
      alpha 6 expression on the surface of SK-MEL-28 melanoma cells was accompanied by
      a reduced ability of the cells to adhere to an artificial basement membrane. In
      conclusion, the present investigation shows that besides having an
      antiproliferative effect on the SK-MEL-28 melanoma cells, 1 alpha,25(OH)2D3 is
      also able to inhibit the surface expression of the alpha 6-subunit of the
      integrin laminin receptor. Moreover, the results strongly indicate that 1
      alpha,25(OH)2D3 exerts its regulatory effect on the alpha 6-subunit at the
      transcriptional level rather than at the protein level.

PMID- 9638333
TI  - Maturation of cell-substratum focal adhesions induced by depolymerization of
      microtubules is mediated by increased cortical tension.
AB  - Dynamics of alterations of focal adhesions (FA) induced by a microtubule
      depolymerizing drug, colcemid, was examined in several types of fibroblastic
      cells. Evolution of individual FA in cultured cells was monitored by interference
      reflection microscopy (IRM); at the end of the monitoring period (3 hours) the
      cells were fixed and immunofluorescence microscopy of the same FA was performed
      with an antibody against vinculin. Control and colcemid-treated cells remained
      non-motile and did not show lamellipodial activity at the edges. During the
      incubation, formation of new FA or disappearance of pre-existing FA did not occur
      in either colcemid-treated or control cultures. However, FA in colcemid-treated
      cells significantly increased in size in the course of a 3 hour incubation. The
      growth of FA was centripetal and sometimes was accompanied by the fusion of
      several adjacent FA. Immunofluorescence examination showed that colcemid-induced
      growth of FA was accompanied by accumulation of several proteins specific for
      these structures including vinculin, talin, paxillin and pp125FAK kinase.
      Immunoblotting with anti-vinculin antibody showed that incubation with colcemid
      considerably increased the amount of vinculin associated with the ventral
      membranes due to its partial redistribution from a soluble pool into the growing
      adhesions. A substantial increase in tyrosine phosphorylation of pp125FAK was
      also observed in colcemid-treated cells. In cells plated on elastic silicone
      rubber films, colcemid induced formation of wrinkles in the films and these
      wrinkles relaxed after treatment with cytochalasin D. These results confirm that
      microtubule depolymerization increases traction transmitted to the substratum by
      the actin cortex and shows that an increase in cortical tension accompanies
      maturation of FA. Taken together, these data show that short-term incubation with
      colcemid does not affect the formation of initial FA. In contrast, microtubule
      depolymerization considerably stimulates the maturation FA, manifested by their
      centripetal growth. Maturation is proposed to be mediated by increased cortical
      tension, which is caused by microtubule depolymerization.

PMID- 9638334
TI  - Calcium-induced intercellular adhesion of keratinocytes does not involve
      accumulation of beta 1 integrins at cell-cell contacts and does not involve
      changes in the levels or phosphorylation of catenins.
AB  - On initiation of terminal differentiation human epidermal keratinocytes detach
      from the underlying basement membrane as a result of inactivation and subsequent
      loss of integrins from the cell surface. Assembly of keratinocytes into
      multilayered sheets requires functional E- and P-cadherin and when stratification
      is inhibited in low calcium medium differentiating keratinocytes continue to
      express functional integrins. Using immunofluorescence microscopy, we found that
      on addition of calcium ions to keratinocyte monolayers there was colocalisation
      of the beta 1 integrins and E-cadherin along the lateral membranes except for a
      zone close to the substratum which exclusively contained integrins. Quantitative
      immunoelectron microscopy showed that on induction of stable cell-cell contacts
      the density of beta 1 integrins was the same on the apical and lateral membranes,
      suggesting that the accumulation of integrins on the lateral membranes observed
      by immunofluorescence microscopy is due to the increased area of contact between
      adjacent cells and not to an increase in receptor density. There were no changes
      in the levels of catenins and their degree of phosphorylation after induction of
      cell-cell contacts. These observations provide new sights into the mechanism of
      calcium-dependent intercellular adhesion of keratinocytes.

PMID- 9638335
TI  - CD43 (sialophorin, leukosialin) shedding is an initial event during neutrophil
      migration, which could be closely related to the spreading of adherent cells.
AB  - Leukosialin is a negatively-charged mucin-like membrane protein of leukocytes.
      This anti-adhesive molecule prevents uncontrolled cellular interactions and is
      proteolytically cleaved during neutrophil activation. CD43 is shed in vivo during
      neutrophil migration to the inflammatory site. We have analysed the decrease in
      CD43 expression during in vitro adherence of TNF-alpha activated PMN. CD43 was
      quantitated by flow cytometry on TNF-alpha-activated PMN either maintained in
      suspension or allowed to adhere then detached with EDTA. Although TNF did not
      induce significant modification of CD43 expression on suspended cells, we showed
      that 40% of membrane CD43 is released during neutrophil TNF-induced adhesion to
      serum-coated plates or endothelial cells, and that migration through the
      endothelial monolayer did not result in further shedding. Adhesion-blocking anti
      beta 2 integrin mAbs prevented CD43 shedding. beta 2 integrin "activation" by
      anti-CD 18 mAbs or Mn ions did not decrease CD43 expression if adhesion was
      prevented by stirring. Inhibitors of signal transduction or of cytoskeleton
      association, which allowed cells to adhere but not to spread, inhibited the
      shedding of CD43 during adhesion. We conclude that CD43 shedding is not promoted
      by beta 2 integrins engagement or adhesion but is concomitant with spreading of
      adherent cells.

PMID- 9638336
TI  - Distinct location and prevalence of alpha-, beta-catenins and gamma
      catenin/plakoglobin in developing and denervated skeletal muscle.
AB  - We studied the distribution of alpha-catenin, beta-catenin and gamma
      catenin/plakoglobin in developing, adult and denervated mouse skeletal muscle.
      During primary myogenesis, all three catenins present a subsarcolemmal
      distribution within primary myotubes. During secondary myogenesis they accumulate
      at myotube-myotube contacts. In contrast to the other catenins, gamma-catenin is
      strongly expressed in the sarcoplasm. In adult muscle, all three catenins are
      localized on the presynaptic elements of the neuromuscular junction. In
      denervated muscles, alpha- and beta-catenins are upregulated like N- and M
      cadherin, while the levels of gamma-catenin/plakoglobin remain unchanged. The
      developmental changes in localization and regulation of alpha- and beta-catenins
      in muscle compared to gamma-catenin/plakoglobin are suggestive of a privileged
      association of alpha- and beta-catenins with N- and M-cadherins, while gamma
      catenin/plakoglobin appears to be expressed quite independently and must assume a
      different role during myogenesis.

PMID- 9638337
TI  - Desmosomes are regulated by protein kinase C in primary rat epithelial cells.
AB  - In the present study, we addressed the possible relevance of protein kinase C
      (PKC) in the regulation of intracytoplasmic desmosome assembly. Treatment of
      cultured rat lingual and epidermal keratinocytes with a potent and highly
      selective PKC inhibitor (GF109203X) induced an increase in granular labelling for
      major desmosomal proteins, desmoplakins, desmoglein and plakoglobin, both
      intracellularly and at the cell surface. This was associated with the formation
      of ultrastructurally recognizable desmosomes deep in the cytoplasm and increase
      in intercellular desmosome number. In contrast, PKC activation upon short
      exposure to 12-O-tetradecanoylphorbol 13-acetate (TPA) resulted in altered cell
      morphology, loss of intercellular contact and accumulation of desmosomal proteins
      in the juxtanuclear zone. On the other hand, PKC depletion by long term TPA
      treatment re-established cell-cell contact, where desmosomal markers were
      exclusively redistributed. Taken together, these results suggest that inhibition
      of PKC is required for intracytoplasmic as well as intercellular desmosome
      assembly, whereas its activation may regulate disassembly process.

PMID- 9638338
TI  - Cadherin mediated cell-cell adhesion is regulated by tyrosine phosphatases in
      human keratinocytes.
AB  - Normal Human Keratinocytes express on their cell surface E- and P-cadherins, two
      Ca2+ dependent homophilic cell adhesion molecules that mediate keratinocyte
      keratinocyte adherens junctions. In other cell types, adherens-type junctions are
      reported to be major subcellular targets for tyrosine specific protein
      phosphorylation (Volberg et al. (1991) Cell Regul., 2, 105-120) involving
      tyrosine kinases and tyrosine phosphatases. We investigated the role of tyrosine
      phosphatases in the regulation of cadherin mediated keratinocyte-keratinocyte
      adhesion. We report the results of a wide tyrosine phosphatase inhibition using
      pervanadate, a modified vanadate derivative known to inhibit most tyrosine
      phosphatases. Keratinocytes treated with pervanadate, exhibit an important change
      in cellular morphology and cadherins/catenins localization as shown by phase
      contrast microscopy and immunocytochemistry. In this conditions, cadherins and
      catenins no longer colocalize with the actin cytoskeleton of cells and the amount
      of E-cadherin bound to the cytoskeleton decreases. A more intense phosphotyrosine
      labelling is seen at the edges of the treated cells, suggesting that an increase
      in the phosphorylation rate of some cadherin-catenin complex proteins induces a
      diminished intercellular adhesion. Finally immunoprecipitation experiments of the
      E-cadherin/catenin complex from pervanadate treated keratinocytes reveal an
      increase in the tyrosine phosphorylation rate of E-cadherin, beta catenin and
      probably gamma catenin. These data suggest an essential role for the protein
      tyrosine phosphatases in keratinocyte intercellular junctions.

PMID- 9638339
TI  - Dependence of neutrophil activation on cell density and adhesion.
AB  - Upon an increasing cell density human neutrophils develop more cell-to-cell
      contacts in conjunction with an increase in the pHi. These changes are
      accompanied by decreased superoxide formation after adherence, and a decrease in
      the total amount of 5-lipoxygenase products after various stimuli. Among the
      various arachidonate metabolites, leukotriene formation remained almost constant
      but the yield in 5-HETE decreased. This drop in could account for the decrease in
      total 5-lipoxygenase products observed when the cell density increased. We
      conclude that cellular signalling can be affected by an increase of cell-cell
      interactions. Whether the increase in cellular pH is a cause or consequence of
      such contact inhibition has yet be answered.

PMID- 9638340
TI  - Early atherosclerotic plaques in the aorta following cytomegalovirus infection of
      mice.
AB  - We show here that BALB/c mice inoculated with murine cytomegalovirus (MCMV)
      express viral antigens in the endothelial and smooth muscle cells of the aortic
      wall, and that accumulation of inflammatory cells in the aortic lumen, similar to
      that seen in early atherosclerotic lesions in humans, colocalizes with the site
      of virus antigen expression. Immunosuppression of the mice at the time of virus
      infection increased the expression of viral antigens and the size of early
      atherosclerotic lesions in the intima. The percentage of the low-density
      lipoprotein cholesterol (LDL-C), the major lipid contributor to atherosclerotic
      plaques, was significantly increased in the serum of MCMV-infected mice, whether
      or not the mice were fed a high cholesterol diet. Human cytomegalovirus (HCMV)
      significantly increased the esterified cholesterol component of the total
      cholesterol in a human arterial smooth muscle cell line infected in vitro with
      HCMV. These results suggest that CMV infection is involved in two of the major
      mechanisms that lead to development of atherosclerosis, i.e., immune injury and
      high LDL-C.

PMID- 9638341
TI  - Vinculin and cell-cell adhesion.
AB  - Vinculin, a 117-kDa protein, is a constituent of adhesion plaques and adherence
      junctions in non-muscle cells. We investigated the role of vinculin on the
      physical strength of cell-cell adhesion by conducting disaggregation assays on
      aggregates of parental wild-type F9 mouse embryonal carcinoma cells (clone BIM),
      two vinculin-depleted F9 cell lines, gamma 227 and gamma 229, and a reconstituted
      gamma 229 cell line (R3) that re-express vinculin. Immunoblotting demonstrated
      that the four cell lines used in the study had similar expressions of the cell
      cell adhesion molecule E-cadherin and associated membrane proteins alpha- and
      beta-catenin. Double immunofluorescence analysis showed that, in contrast to the
      vinculin-null cell lines. BIM and R3 cells expressed abundant vinculin at the
      cell margins in adhesion plaques and in cell-cell margins that also contained
      actin. Laminar flow assays showed that both the vinculin-positive and vinculin
      negative cell aggregates that were formed in culture in the course of 24 to 48
      hours largely remained intact despite the imposition of shear flow at high shear
      rates. Since laminar flow imposed on cell aggregates act to separate cells from
      each other, our data indicate that F9 cells that were adherent to a substrate
      formed strong cell-cell adhesion bonds independent of vinculin expression. On the
      other hand, aggregates of vinculin-depleted gamma 229 and gamma 227 cells that
      were formed in suspension during a two-hour static incubation at 37 degrees C
      were desegregated more easily with the imposition of shear flow than the BIM and
      R3 cell aggregates formed under identical conditions. Loss of vinculin was
      associated with a reduction in cell-cell adhesion strength only among those cells
      lacking contact to a substrate. Overall, the results indicate that vinculin is
      not needed for forming strong cell-cell adhesion bonds between neighboring
      carcinoma cells which are adherent to the basal lamina.

PMID- 9638342
TI  - A conserved role for L1 as a transmembrane link between neuronal adhesion and
      membrane cytoskeleton assembly.
AB  - The L1-family of cell adhesion molecules is involved in many important aspects of
      nervous system development. Mutations in the human L1-CAM gene cause a
      complicated array of neurological phenotypes; however, the molecular basis of
      these effects cannot be explained by a simple loss of adhesive function. Human L1
      CAM and its Drosophila homolog neuroglian are rather divergent in sequence, with
      the highest degree of amino acid sequence conservation between segments of their
      cytoplasmic domains. In an attempt to elucidate the fundamental functions shared
      between these distantly related members of the L1-family, we demonstrate here
      that the extracellular domains of mammalian L1-CAMs and Drosophila neuroglian are
      both able to induce the aggregation of transfected Drosophila S2 cells in vitro.
      To a limited degree they even interact with each other in cell adhesion and
      neurite outgrowth assays. The cytoplasmic domains of human L1-CAM and neuroglian
      are both able to interact with the Drosophila homolog of the cytoskeletal linker
      protein ankyrin. Moreover the recruitment of ankyrin to cell-cell contacts is
      completely dependent on L1-mediated cell adhesion. These findings support a model
      of L1 function in which the phenotypes of human L1-CAM mutations results from a
      disruption of the link between the extracellular environment and the neuronal
      cytoskeleton.

PMID- 9638343
TI  - Epitope mapping of a function-blocking beta 1 integrin antibody by phage display.
AB  - Integrins are a major class of cell surface receptors involved in cell-cell and
      cell-matrix adhesion and communication. Ha2/11 is a function-blocking anti-rat
      beta 1 integrin hamster IgM that should be a useful reagent for understanding
      beta 1 integrin function. We demonstrate that Ha2/11 cross reacts with human,
      Xenopus, and Drosophila beta 1 integrins, and use phage display to map the
      epitope for Ha2/11 to residues within the sequence LRSGEPQTF which lies 18 amino
      acids proximal to the putative I domain in beta 1 integrins. Monoclonal antibody
      mapping experiments, mutational analyses, and direct binding assays have
      implicated integrin I domains in both cation and ligand binding. Our data
      therefore suggest that Ha2/11 blocks beta 1 integrin function by interfering with
      I domain-mediated ligand binding.

PMID- 9638344
TI  - The biochemistry of gene therapy for AIDS.
AB  - Gene therapy has enormous potential and could in the near future involve the
      clinical biochemist in monitoring its efficacy. The involvement of clinical
      biochemists in this field could be not only in evaluating the impact of a gene
      based strategy on disease progression, but also in measuring the expression of
      the products of therapeutic genes in treated individuals. Indeed, gene therapy
      presents new possibilities for the treatment of many diseases and, in particular,
      merits consideration in the treatment of a fatal disease like AIDS. The aim of
      this paper is to review the biochemical basis and clinical relevance of the gene
      therapy approaches directed towards the inhibition of human immunodeficiency
      virus type-1. We discuss the goals which have been achieved, the problems which
      have occurred and the efforts that are being made to solve them. In this regard,
      particular attention is paid to new strategies targeting 'therapeutic' enzymes to
      human immunodeficiency virus type-1 nucleic acids.

PMID- 9638345
TI  - Reticulocytes and reticulated platelets: simultaneous measurement in whole blood
      by flow cytometry.
AB  - Reticulated platelets are a fraction of newly released circulating elements
      characterized by a residual amount of RNA. It has been suggested that the
      reticulated platelet count, providing an estimate of thrombopoiesis in the same
      way as erythrocyte reticulocyte count is a measure of erythropoiesis, may be
      useful in the study of thrombocytopenic disorders. Reticulated red cells and
      platelets can be analyzed by flow cytometry using specific stains for nucleic
      acids such as Thiazole Orange and Auramine-O. The aim of our work was to perform
      the simultaneous evaluation of reticulated elements in whole blood using a
      standard flow cytometer and to correlate the results obtained with a dedicated
      cytometer. A group of 14 patients with abnormal absolute reticulocyte counts
      (range 1.1-11%) and a group of 41 patients showing a platelet discrimination
      error when analyzed with a dedicated flow cytometer (Sysmex R1000) were enrolled.
      Linear amplification of both scatter and fluorescence was used to perform
      reticulocyte count. A gate was set on platelet dimensions, and logarithmic
      amplification of scatter and fluorescence was used to count reticulated
      platelets. A good correlation was obtained both for results of reticulocyte count
      (r2 = 0.9825) and for reticulated platelets (r2 = 0.8717) between our method and
      those using dedicated instruments. These data show that reticulated platelet
      count may be easily introduced in clinical laboratories that routinely perform
      reticulocyte count by flow cytometry.

PMID- 9638346
TI  - Salivary cortisol--an alternative to serum cortisol determinations in dynamic
      function tests.
AB  - Salivary cortisol was measured as an alternative to serum cortisol as a marker
      for adrenocortical function following insulin tolerance test, corticotropin
      releasing-hormone stimulation and adreno-corticotrophic hormone stimulation.
      During insulin tolerance test and corticotropin-releasing-hormone stimulation
      adreno-corticotrophic hormone was also measured. The tests were performed on
      healthy control subjects as well as on patients under investigation for various
      disturbances in the hypothalamic-pituitary-adrenocortical axis (insulin tolerance
      test: 3 controls on two occasions and 14 patients; corticotropin-releasing
      hormone stimulation: 4 controls and 18 patients; adreno-corticotrophic hormone
      stimulation: 6 controls and 10 patients). Five patients underwent both insulin
      tolerance test and corticotropin-releasing-hormone stimulation. Using criteria
      for adequate cortisol response in serum, the patients were classified as good or
      poor responders. In 42 of the 45 tests performed the same conclusion as to
      cortisol status was drawn when based on serum and salivary cortisol responses. In
      healthy subjects and good responders the mean cortisol relative increase was
      greater in saliva than in serum in all three tests (p < 0.05). Characteristic of
      the results for the insulin tolerance test was a significant initial mean
      decrease (p < 0.05), not found in serum, and the highest observed salivary
      cortisol value was delayed for at least 30 minutes compared to that in serum.
      Plasma adreno-corticotrophic hormone correlated significantly with the cortisol
      concentrations determined 15 minutes later in serum (r = 0.54-0.64) and in saliva
      (r = 0.76-0.85). The more pronounced cortisol response in saliva than in serum
      and its closer correlation with adreno-corticotrophic hormone offer advantages
      over serum cortisol, suggesting salivary cortisol measurement may be used as an
      alternative parameter in dynamic endocrine test.

PMID- 9638347
TI  - A time-resolved fluorescence immunoassay for the measurement of testosterone in
      saliva: monitoring of testosterone replacement therapy with testosterone
      buciclate.
AB  - Monitoring of testosterone replacement therapy requires a reliable method for
      testosterone measurement. Determination of salivary testosterone, which reflects
      the hormone's biologically active plasma fraction, is a superior technique for
      this purpose. The aim of the present study was to establish a new sensitive time
      resolved fluorescence immunoassay for the accurate measurement of testosterone
      levels in saliva and to validate it by monitoring testosterone replacement
      therapy in eight hypogonadal men. A clinical phase I-study with the new ester
      testosterone buciclate was performed to search for new testosterone preparations
      to produce constant serum levels in the therapy of male hypogonadism. After two
      control examinations eight male patients with primary hypogonadism were randomly
      assigned to two treatment groups (n = 2 x 4) and given single doses of either 200
      mg (group I) or 600 mg (group II) testosterone buciclate intramuscularly. Saliva
      and blood samples were obtained 1, 2, 3, 5 and 7 days post injection and then
      weekly for three months. The time-resolved fluorescence immunoassay for salivary
      testosterone shows a detection limit of 16 pmol/l, an intra-assay CV of 8.9% (at
      a testosterone concentration of 302 pmol/l), an inter-assay CV of 8.7% (at a
      testosterone concentration of 305 pmol/l) and a good correlation with an
      established radioimmunoassay of r = 0.89. The sample volume required by this
      method is only 180 microliters for extraction and duplicate determination. The
      assay procedure requires no more than three hours. In group I (200 mg)
      testosterone did not increase to normal levels either in saliva or in serum.
      However, in group II, androgen levels increased significantly and were maintained
      in the normal range for up to 12 weeks with maximal salivary testosterone levels
      of 303 +/- 18 pmol/l (mean +/- SE) and maximal testosterone levels of 13.1 +/-
      0.9 nmol/l (mean +/- SE) in serum in study week 6 and 7. The time-resolved
      fluorescence immunoassay for salivary testosterone provides a useful tool for
      monitoring androgen status in men and women and is well suited for the follow-up
      of testosterone replacement therapy on an outpatient basis. The long-acting ester
      testosterone buciclate is a promising agent for substitution therapy of male
      hypogonadism and in combination with testosterone monitoring in saliva offers an
      interesting new perspective for male contraception.

PMID- 9638348
TI  - External quality assessment of molecular biology-based methods used in
      laboratories of clinical chemistry and human genetics.
AB  - The Reference Institute of Bioanalysis of the German Society of Clinical
      Chemistry has performed the first external assessment of molecular genetics
      methods used in medical diagnosis. The following procedures were tested: (I) DNA
      preparation from whole blood, (II) PCR amplification using "standard" primers,
      and (III) submarine agarose gel electrophoresis. Out of 50 participants, 45
      returned samples for evaluation.

PMID- 9638349
TI  - Preoperative values of molecular coagulation markers identify patients at low
      risk for intraoperative haemostatic disorders and excessive blood loss.
AB  - Conventional laboratory investigations of haemostasis like prothrombin time and
      activated partial thromboplastin time are not useful in predicting and managing
      intra-operative bleeding complications. In order to establish a possible
      "perioperative reference range" for thrombin generation prothrombin fragment F1+2
      (F1+2) and fibrin degradation (D-dimer) markers, we measured F1+2 and D-dimer
      concentrations before surgery (but after induction of anaesthesia), 30 minutes
      into surgery, 10 minutes after the event expected to induce the maximal
      activation of the haemostatic systems, 90 minutes after surgery and on
      postoperative days 1 and 2 in 226 consecutive patients. Samples were collected
      from arterial lines. Twenty patients developed a clinically defined,
      intraoperative disorder of haemostasis, 206 did not. Patients with an
      intraoperative disorder of haemostasis had significantly higher preoperative F1+2
      and D-dimer concentrations. Preoperative values for F1+2 and D-dimer
      concentrations above the 75th percentile of patients without an intraoperative
      disorder of haemostasis indicated a 2.70 to 2.88 fold risk of developing an
      intraoperative disorder of haemostasis (odds ratios were 3.04, 3.12 and 3.29 for
      D-dimer, ELISA, F1+2, and D-dimer latex tests, respectively with 95% confidence
      intervals from 1.20 to 8.46) with negative predictive values of 94%, but positive
      predictive values of only 16% to 26%. These data suggest that preoperative
      determination of molecular markers might be helpful in identifying a group of
      patients at high risk for intraoperative disorder of haemostasis by exclusion of
      low risk patients. Validation of such an approach requires a prospective trial.

PMID- 9638350
TI  - Rifampicin causes false-positive immunoassay results for urine opiates.
AB  - The treatment of tuberculosis usually includes the antibiotic rifampicin,
      especially in patients with concomitant human immunodeficiency virus infection.
      Some of these patients are in withdrawal therapy for drug abuse. When opiate
      screening is carried out in patients receiving rifampicin, false positive results
      are detected with the kinetic interaction of microparticles in solution method.
      We evaluated this interference in a Cobas-Integra analyzer and found a 12% cross
      reactivity of rifampicin for antibiotic concentrations ranging from 0.19 to 6.08
      mumol/l (156 to 5000 micrograms/l). This effect is not explained by the colour of
      the rifampicin solutions. Calculations assuming first order kinetics of
      elimination show that more than 18 hours after a single oral dose of 600 mg of
      rifampicin, a false positive result for opiates could be obtained. This indicates
      that the risk of a false positive result must always be considered when urine
      samples from these patients are analyzed.

PMID- 9638351
TI  - Neuron-specific enolase: reference values in cord blood.
AB  - With foetal sonography prenatal detection of tumours has become more frequent. To
      evaluate and treat these infants it is necessary to identify the tumour
      postnatally. Elevated neuron-specific enolase is a biochemical marker of
      neuroblastoma. Since conditions during birth may influence neuron-specific
      enolase concentration in foetal serum, specific reference values in cord blood
      are required. Cord blood samples were taken from 192 healthy term newborns and
      concentration of neuron-specific enolase was measured by enzyme immunoassay
      (EIA). Median neuron-specific enolase concentration in the reference group was
      8.0 micrograms/l and the 5th-95th percentiles were 4.8-19.4 micrograms/l. No
      differences between male and female newborns were detected (p = 0.13).
      Measurement of neuron-specific enolase in cord blood, in comparison with our
      reference values, offers an early postnatal possibility of confirming the
      diagnosis of neuroblastoma.

PMID- 9638352
TI  - Additional Essential Criteria for Quality Systems of Medical Laboratories.
      European Community Confederation of Clinical Chemistry (EC4) Working Group on
      Harmonisation of Quality Systems and Accreditation.
AB  - Essential Criteria for Quality Systems of Medical Laboratories have been
      published recently by the European Community Confederation of Clinical Chemistry
      (EC4) Working Group on Harmonisation of Quality Systems and Accreditation. The
      Essential Criteria address the majority of critical aspects of quality management
      in the medical laboratory. They have been accepted by the EC4 General Assembly
      and are endorsed by the Forum of European Societies for Clinical Chemistry
      (FESCC). However, a supplement to the Essential Criteria was necessary,
      addressing two aspects, which are only partly covered by the Essential Criteria:
      the management of resources and point of care testing. Thus, the EC4 Working
      Group on Harmonisation of Quality Systems and Accreditation has decided to
      formulate Additional Essential Criteria for Quality Systems of Medical
      Laboratories, directed at the issues of management of resources and point of care
      testing. Criteria on management of resources address financial aspects,
      information logistics and acceptance by clients. Criteria on point of care
      testing address responsibilities, education of non-laboratory staff and
      operational aspects. The Additional Criteria are supplementary to the previously
      published Essential Criteria and should be read as an integral part of these.

PMID- 9638353
TI  - Low concentration monoclonal and oligoclonal bands in serum and urine using the
      Sebia Hydragel Protein Electrophoresis System.

PMID- 9638354
TI  - Neglected topics in eating disorders: guidelines for clinicians and researchers.
AB  - Over the past few decades, there has been significant progress in research on
      eating disorders that has informed the clinical management of these difficult,
      and sometimes refractory, disorders. Indeed, sufficient progress has been made
      such that practice guidelines have been offered to delineate standards of
      clinical care and guidance to clinicians in the treatment of bulimia nervosa and
      anorexia nervosa. Out of necessity, however, the practice guidelines are based on
      a combination of research-based recommendations and clinical consensus because of
      significant gaps in the extant research. Nonetheless, clinicians must confront
      these clinical issues. The purpose of this special series is to address areas of
      significant clinical importance that have a very modest research literature, and
      to briefly summarize the existing research. The authors of the individual papers,
      all noted experts in eating disorders treatment, then offer practical clinical
      management recommendations drawing both on the modest available research and
      their extensive clinical experience.

PMID- 9638355
TI  - Enhancing motivation for change in treatment-resistant eating disorders.
AB  - Denial and resistance to change are prominent features in most patients with
      anorexia nervosa. The egosyntonic quality of symptoms can contribute to
      inaccuracy in self-report, avoidance of treatment, difficulties in establishing a
      therapeutic relationship, and high rates of attrition and relapse. Individuals
      with bulimia nervosa are typically more motivated to recover, but often
      ambivalent about forfeiting the ideal of slenderness and the protective functions
      of binge-purge behavior. Few attempts have been made to assess denial and
      resistance in the eating disorders, or to examine alternative strategies for
      enhancing motivation to change. Review of the clinical literature indicates a
      striking convergence of recommendations across conceptually distinct treatment
      approaches. Clinicians are encouraged to acquire a frame of reference that can
      help them understand the private experience of individuals with eating disorders,
      empathize with their distress at the prospect of weight gain, and acknowledge the
      difficulty of change. The Socratic method seems particularly well-suited to work
      with this population because of its emphasis on collaboration, openness,
      curiosity, patience, focused and systematic inquiry, and individual discovery.
      Four themes are crucial in engaging reluctant eating-disordered clients in
      therapy: the provision of psychoeducational material, an examination of the
      advantages and disadvantages of symptoms, the explicit use of experimental
      strategies, and an exploration of personal values.

PMID- 9638356
TI  - Treatment of eating disorders in children and adolescents.
AB  - Anorexia nervosa and bulimia nervosa are expressed differently in children and
      adolescents than in adults. Consequently, diagnostic procedures and
      multidisciplinary treatments need to be tailored to the unique developmental,
      medical, nutritional, and psychological needs of children and adolescents with
      eating disorders. This paper reviews current research outlining the differences
      between child, adolescent, and adult eating disorders. Research is then reviewed
      concerning the effectiveness of hospitalization, partial hospitalization,
      individual dynamic therapy, cognitive-behavioral therapy, interpersonal therapy,
      family therapy, and medication for treating anorexia nervosa, bulimia nervosa,
      and related eating disorders in children and adolescents. Specific
      recommendations are made for practitioners to tailor these treatments to their
      eating-disordered child and adolescent patients, following a stepped-care,
      decision-tree model of intervention that takes into account the effectiveness,
      cost, and intrusiveness of the interventions.

PMID- 9638357
TI  - Long-term course of anorexia nervosa: response, relapse, remission, and recovery.
AB  - There is no predictable or normative long-term course associated with anorexia
      nervosa. Some Individuals achieve complete recovery; others are ravaged by a
      chronic disorder; and some die from it. Predicting course and outcome of anorexia
      nervosa is complicated by the intrinsic complexity of the disorder; a lack of
      shared terminology in studying the disorder; and a paucity of controlled clinical
      treatment studies. This manuscript provides a review of the current state of
      knowledge based on the long-term studies and discusses ways in which
      methodological issues limit our ability to generalize more confidently regarding
      the course and outcome of anorexia nervosa. In order to advance the field, we
      need to bridge the gap between treatment outcome studies and naturalistic follow
      up studies. Further we need to devine more carefully and consistently the
      milestones of initial treatment response, relapse, remission, and recovery.
      Building on previous works, criteria for each of these terms are proposed. Based
      on existing studies, a discussion of treatment outcome and prognostic factors is
      provided. Finally, clinical recommendations are provided for the clinician who is
      responsible for the long-term care of an individual with anorexia nervosa.

PMID- 9638358
TI  - Lymphocyte activation and effector functions. Web alert.

PMID- 9638359
TI  - Germinal centers: form and function.
AB  - Our understanding of the formation of germinal centers has advanced considerably
      during the past year. Highlights include the elucidation of the role of cytokines
      and chemokines in splenic organization and lymphocyte migration and their roles
      in germinal center development. The functional consequences of recombination
      activating gene re-expression in the germinal center have also been reported, as
      have in vitro models of somatic mutation. Finally the resolution of the germinal
      center reaction is being addressed by analysis of the individual cell types
      produced.

PMID- 9638360
TI  - Long-lived plasma cells: a mechanism for maintaining persistent antibody
      production.
AB  - Current models suggest that continuous antigenic stimulation of memory B cells is
      required to maintain long-term antibody production. In view of recent
      developments concerning plasma cell longevity, a new model is described that
      incorporates the important role of long-lived plasma cells in sustaining
      persistent antibody responses.

PMID- 9638361
TI  - Regulation of interferon-gamma production by IL-12 and IL-18.
AB  - IL-18 (interferon-inducing factor) and IL-12 exhibit a marked synergism in
      interferon-gamma induction in T cells. Investigations into the mechanism of this
      synergism have revealed that IL-12 upregulates expression of the IL-18 receptor
      on cells producing interferon-gamma. Although IL-18 does not induce the
      development of Th1 cells, it is essential for the effective induction and
      activation of Th1 cells by IL-12. As for natural killer cells, IL-18 seems to
      activate them independently of IL-12. Although IL-12 and IL-18 activate both
      innate and acquired immunity, their excessive production by activated macrophages
      may induce multiple organ disorders including disruption of the immune system.

PMID- 9638362
TI  - Chemokines, lymphocytes and viruses: what goes around, comes around.
AB  - Chemokines are believed to be the long-sought soluble mediators of selective
      lymphocyte recruitment. As most selectin-integrin interactions are nonselective,
      it is thought that the discrimination seen during lymphocyte infiltration into
      tissues is brought about by the actions of distinct chemokines. Developments over
      the past year have demonstrated the expanding roles of these factors in
      lymphocyte chemoattraction, normal trafficking, and viral immunity.

PMID- 9638363
TI  - JAK/STAT signaling by cytokine receptors.
AB  - The JAK/STAT pathway is recognized as one of the major mechanisms by which
      cytokine receptors transduce intracellular signals. This system is regulated at
      multiple levels, including JAK activation, nuclear trafficking of STAT factors,
      and negative feedback loops. Gene deletion studies have implicated selected STAT
      factors as predominant mediators for a limited number of lymphokines. This
      signaling pathway influences normal cell survival and growth mechanisms and may
      contribute to oncogenic transformation.

PMID- 9638364
TI  - Death-inducing functions of ligands of the tumor necrosis factor family: a
      Sanhedrin verdict.
AB  - Members of the tumor necrosis factor ligand family can kill cells in a rather
      straightforward manner. They induce their receptors to recruit and activate
      caspases, enzymes that are critically involved in the death process, and this
      activation is further amplified by intracellular mitochondria-associated
      mechanisms. The potentially hazardous expression of the ligands occurs widely in
      the body; it is antigen-restricted only in the lymphocytes. Yet, in addition to
      control modes affecting ligand expression, there are numerous inhibitory
      mechanisms that act within target cells, to make doubly sure of avoiding an undue
      'death verdict', while allowing the cells to exhibit other, noncytocidal effects
      of the ligands.

PMID- 9638365
TI  - Cytokine regulation of secondary lymphoid organ development.
AB  - Lymphotoxin and tumor necrosis factor provide essential signals for the formation
      of secondary lymphoid tissue structures. Lymphotoxin in its membrane form (LT
      alpha 1 beta 2 heterotrimer) is required for the development of lymph nodes and
      Peyer's patches and supports the development of normal spleen structure. In the
      spleen, lymphotoxin acts during embryonic development to support the formation of
      distinct B and T cell zones. Lymphotoxin also acts in a tonic fashion-supporting
      the formation and maintenance of the follicular dendritic cell network and of
      primary B cell follicle structure. The cells that deliver the tonic lymphotoxin
      signal supporting follicular dendritic cell structure are B cells; thus, B cells
      participate fundamentally in the development of the lymphoid tissue structure in
      which they subsequently mature.

PMID- 9638366
TI  - Natural killer cell receptors.
AB  - In killing of cellular targets, natural killer cells employ receptors that
      activate them and receptors specific for MHC class I that inhibit their
      activation. Progress in understanding the inhibitory receptors has been rapid,
      and indications are that they fall into two distinct structural types that appear
      to utilize the same inhibitory signaling cascade; meanwhile, components of the
      activation cascade are being elucidated, permitting us to integrate the pathways
      involved.

PMID- 9638367
TI  - Inhibitory signaling by B cell Fc gamma RIIb.
AB  - The fact that B cells undergo feedback suppression, or negative signaling,
      through the interaction of secreted antibody with specific antigen has been
      extensively documented but the mechanisms involved in the process have been
      elusive. Experiments over the past year using B cell deletion mutants and
      dominant-negative enzymes have firmly established an important role for SH2
      domain-containing inositol 5-phosphatase (SHIP) in negative signaling. Negative
      signaling through SHIP appears to inhibit the Ras pathway through SH2 domain
      competition with Grb2 and Shc and may involve consumption of intracellular lipid
      mediators that act as allosteric enzyme activators or that promote entry of
      extracellular Ca2+.

PMID- 9638368
TI  - Negative regulation of T cell activation.
AB  - T cell activation is negatively regulated by cytotoxic T lymphocyte antigen 4
      (CTLA-4) and the killer cell inhibitory receptors. Endocytosis and signaling of
      CTLA-4 are regulated by tyrosine phosphorylation. While T cell activation is
      mediated by phosphorylation of immunoreceptor tyrosine-based activation motifs
      and tyrosine kinases, inhibitory signals are delivered by tyrosine phosphatases.
      Unresponsiveness is also induced by modulation of signaling components of the T
      cell receptor complex.

PMID- 9638369
TI  - GTPases in antigen receptor signalling.
AB  - Immunological interest in small GTPases has focused for some years almost
      exclusively on the role of Ras in promoting lymphocyte activation and
      development. A new concept in this field is that GTPases are linked to multiple
      biochemical effector signalling pathways and are consequently able to regulate
      diverse cellular processes. It is also now recognised that GTPases other than Ras
      regulate lymphocyte biology. Rap 1 has been suggested as a negative regulator of
      lymphocyte responses and Rho GTPases are important components of signalling
      pathways used by antigen receptors and by costimulatory, cytokine and chemokine
      receptors to regulate the immune response.

PMID- 9638370
TI  - Mammalian target of rapamycin: immunosuppressive drugs uncover a novel pathway of
      cytokine receptor signaling.
AB  - Recent findings have significantly advanced our understanding of the mechanism by
      which the potent immunosuppressive drug rapamycin inhibits cytokine-dependent
      lymphocyte proliferation. The protein targeted by the immunophilin-rapamycin
      complex is a member of a newly defined family of phosphoinositide-3-kinase
      related kinases. The rapamycin target protein functions as a protein kinase in a
      signal transduction pathway that regulates the synthesis of proteins required for
      cell-cycle progression in both lymphoid and nonlymphoid cells.

PMID- 9638371
TI  - Adaptor proteins in lymphocyte antigen-receptor signaling.
AB  - Adaptor molecules, proteins that possess no intrinsic enzymatic function, but
      which mediate protein-protein interactions, have a critical role in integrating
      signal transduction pathways following engagement of cell-surface receptors.
      Several newly described adaptor molecules have been shown to serve important
      functions in the regulation of signaling events initiated by lymphocyte antigen
      receptors. Understanding how these adaptor proteins function to modulate
      signaling cascades will provide important insights into the complex biology of
      lymphocyte activation.

PMID- 9638372
TI  - Long-range transcriptional regulation of cytokine gene expression.
AB  - Most studies on the control of cytokine gene expression have involved the
      functional analysis of proximal promoters. Recent work has identified distal
      elements that mediate long-range cytokine gene regulation and has implicated
      chromatin reorganization in regulation of cytokine gene loci. These studies have
      begun to elucidate the basis for cell-specificity and high-level expression of
      cytokine genes.

PMID- 9638373
TI  - The regulation and roles of Rel/NF-kappa B transcription factors during
      lymphocyte activation.
AB  - The activation of B and T cells by a wide range of stimuli can rapidly induce
      specific gene expression via a mechanism that promotes the nuclear translocation
      of different Rel/nuclear factor-kappa B (NF-kappa B) transcription factors which
      are normally resident in the cytoplasm. Recent findings highlight the crucial
      roles of specific Rel/NF-kappa B family members in the processes of cell
      division, apoptosis and differentiation that accompany lymphocyte activation.

PMID- 9638374
TI  - Signaling checkpoints during the development of T lymphocytes.
AB  - Two major lineage decisions face immature T cells as they develop in the thymus.
      At an early stage in their development, they must first commit to either the
      gamma delta or alpha beta lineages. If they opt for the alpha beta lineage, then
      at a later stage they must also choose between a CD4+ or CD8+ fate before they
      can pass through the thymic medulla and exit to the periphery. Thymocyte survival
      at key developmental checkpoints is determined by signaling from cytokine
      receptors and the T-cell receptor. Recent advances have been made in contemporary
      understanding of the signals that regulate thymocyte survival, proliferation and
      lineage decisions.

PMID- 9638375
TI  - False-negative cervical smears: medico-legal fallacies and suggested remedies.

PMID- 9638376
TI  - A case-control study of true-positive versus false-negative cervical smears in
      women with cervical intraepithelial neoplasia (CIN) III.
AB  - Cervical smears (n = 150) from five departments showing high-grade dyskaryosis
      were examined by three cytologists. All the smears came from patients with biopsy
      proven CIN III. One hundred had been correctly reported (true positives) but 50
      had originally been reported as negative and had been found to be positive only
      on review (false negatives). There were significant differences between the two
      sets in the characteristics of the dyskaryotic cell population. The false
      negative smears tended to have fewer than 200 dyskaryotic cells. The nuclei of
      the dyskaryotic cells tended to have fine rather than coarse nuclear chromatin. A
      smear with fewer than 50 dyskaryotic cells is 26 times more likely to be reported
      as negative than one with more than 200 dyskaryotic cells. The results suggest
      that there is a type of severely dyskaryotic smear that is inherently likely to
      be missed on routine screening.

PMID- 9638377
TI  - Personal performance profiles: a useful adjunct to quality assurance in cervical
      cytology.
AB  - In our laboratory, which processes approximately 40,000 smears annually, the
      reporting patterns of each individual primary screener have been continuously
      monitored over a 6-year period. The detection rates for minor abnormalities
      (borderline/mild dyskaryosis) and major abnormalities (moderate dyskaryosis and
      worse) are published quarterly in the laboratory. Individual continuous
      monitoring rapidly identifies screeners with low detection rates. It is a useful
      adjunct to existing methods of quality assurance; rescreening can be more
      appropriately directed to smears reported by screeners with low detection rates.
      It also identifies training needs and may be used to assess the value of update
      courses for each screener. It is a faster method of identifying poor performance
      than rapid review of all smears. The reporting rate of inadequate smears is also
      calculated and published on a quarterly basis. This promotes a degree of
      uniformity within the laboratory in the rate at which smears are reported as
      inadequate, and also reduces the inadequate rate.

PMID- 9638378
TI  - Achievable laboratory standards; a review of cytology of 99 women with cervical
      cancer.
AB  - The Working Party guidelines are a significant advance in the audit of the
      National Health Service Cervical Screening Programme (NHSCSP), the priority of
      which is to reduce mortality and morbidity from cervical cancer. This study was
      undertaken to apply the guidance on review of screening history to a series of 99
      women with invasive cervical cancer diagnosed in one centre during a 9 year
      period. The majority (approx. 64%) of these women had not been screened within
      the 5 years preceding diagnosis, 25% had negative, inadequate or abnormal smears
      and 6% had previous treatment for cervical intraepithelial neoplasia (CIN). In
      four patients diagnosis was delayed. No standards are yet available to test the
      results of this series of women. Cervical cancer is relatively uncommon, and for
      data to be aggregated and compared across the UK, it is important that strict
      criteria are developed and applied to ensure that recruitment to the Working
      Party categories is uniform and not open to local interpretation. Full review and
      documentation of screening history should be mandatory for all women who develop
      cervical cancer.

PMID- 9638379
TI  - Evaluation of a statistically derived decision tree for the cytodiagnosis of fine
      needle aspirates of the breast (FNAB).
AB  - A decision tree for the diagnosis of FNAB was derived from defined human
      observations using a rule induction method, C4.5 (a derivative of the ID3
      algorithm). This algorithm is an implementation of the top-down induction method
      where the tree is determined iteratively by adding those nodes and branches which
      maximize the information gain at each step. The tree was derived from a training
      set of 200 FNAB with known outcome using 10 defined features (from one observer)
      and patient age. The tree contained a total of seven nodes (six observable
      features and patient age) with eight endpoints (four benign, four malignant). The
      tree was applied to a test set of 400 further FNAB with observations from the
      training observer and produced a sensitivity of 95%, specificity of 93% and a
      positive predictive value (PPV) of a malignant result of 89%. Four trainee
      pathologists were given a training session on the observable features and then
      used the tree to determine outcome in a further 50 FNAB. The observers were blind
      to clinical details apart from age and the endpoints were coded with letters and
      not labelled benign or malignant. The results from these observers produced
      ranges of sensitivity 80-96%, specificity 64-92%, PPV 73-92% and kappa statistics
      (with known outcome) 0.6-0.8. Reported difficulties in using the tree included
      estimation of nuclear size. These results were worse than the performance of the
      observers on a further 50 cases without using the decision tree (sensitivity 80
      100%, specificity 72-100%, PPV 78-100%, kappa 0.72-0.92). The original 50 case
      test set was rerandomized and the four trainee observers made all 10 defined
      observations on each specimen without using the decision tree; these observations
      were then used to derive decisions from the tree. The performance from this
      method was similar to that using selected features from the tree, suggesting that
      observation of all features together does not improve the reliability of each
      specific observation. The poor performance of this tree suggests that this
      methodology may be unsuitable for producing decision support aids for diagnostic
      or training purposes in this domain.

PMID- 9638380
TI  - A 3-year audit of thyroid fine needle aspirates.
AB  - Fine needle aspiration (FNA) cytology is an important adjunct to the preoperative
      management of thyroid swellings. It is a simple and highly cost effective
      procedure with a higher sensitivity for the detection of malignancy than
      ultrasound and radio-isotope scans. We audited a total of 208 aspirates performed
      over a 3-year period. In our experience 61% of solitary thyroid swellings can be
      diagnosed confidently on FNA cytology as either non-neoplastic (46%) or
      neoplastic (15%). Based on these two groups the sensitivity is 91% and
      specificity 94%. The specificity, however, decreases to 40% if the group reactive
      vs neoplastic, which comprises 10-15% of cases and requires surgical
      intervention, is included. The positive predictive value for malignant disease is
      94% while the false-negative and -positive rates excluding the unsatisfactory and
      reactive vs neoplastic groups are low at 2.7% and 5.4%, respectively (involving
      non-neoplastic lesions and benign tumours only). There was no case of malignant
      cytology with a benign biopsy follow up.

PMID- 9638381
TI  - Pitfalls in the diagnosis of papillary carcinoma of the thyroid.

PMID- 9638382
TI  - Fine needle aspiration (FNA) cytology in tuberculous lymphadenitis.
AB  - Sixty-three lymph node aspirates were screened and 32 aspirates revealing
      granulomatous lymphadenitis with or without caseation necrosis were re-evaluated.
      The most characteristic morphological features among these cases were epithelioid
      cell clusters with or without caseation necrosis. When clusters were thick,
      careful observation of the periphery of the clusters helped to find epithelioid
      cells. Caseation necrosis revealed a typical macroscopic and microscopic
      appearance. Ziehl-Neelsen staining was negative in all smears and histological
      sections. Polymerase chain reaction (PCR) amplification technique was applied to
      23 of the cases in which the cytological diagnoses were consistent with
      tuberculosis. Mycobacterium tuberculosis was demonstrated in 19 (82.60%) cases.
      IN CONCLUSION: (i) it is necessary to perform several aspirations from different
      sites of the enlarged lymph node; (ii) the diagnosis of 'granulomatous
      lymphadenitis, consistent with tuberculosis' can be given, even though the acid
      fast stains are negative; (iii) additional techniques such as PCR give supportive
      information; (iv) an open biopsy is recommended if there is a discrepancy with
      the clinical impression.

PMID- 9638383
TI  - AFB staining in cytodiagnosis of tuberculosis without classical features: a
      comparison of Ziehl-Neelsen and fluorescent methods.
AB  - Fine needle aspirates (FNA) were obtained from lymph node and other sites in 250
      suspected cases of tuberculosis. Twenty-four cases proved to be non-tubercular on
      FNA smears and served as negative controls. Of the smears obtained from the
      remaining 226 cases, 233 were classified into five groups based on
      cytomorphological features, i.e. presence of necrosis and granulomas, necrosis
      alone or acute inflammatory exudate (AIE) with or without granuloma. Cases with
      AIE alone formed the largest group (n = 123). Staining for AFB was done by Ziehl
      Neelsen (ZN) and fluorescent methods in all 250 cases. A correlation of AFB
      positivity and its semiquantitative scoring (1+ to 3+) with the cytomorphological
      spectrum was done. Overall AFB positivity by ZN staining was 33.5% and by
      fluorescent staining 45.4%. When the two methods were combined, AFB positivity
      was 58.7%. Fluorescent staining was superior to the ZN stain in the presence of a
      low bacterial load as seen in smears with diagnostic cytomorphological features
      of tuberculosis. In problem areas like AIE alone or with occasional granulomas,
      AFB positivity by ZN staining is nearly as good as the fluorescent method,
      because the bacterial load is high.

PMID- 9638384
TI  - Fine needle aspiration diagnosis of subcutaneous and osteolytic rhinosporidiosis.

PMID- 9638385
TI  - Drug-food interactions in hospitalised patients. Methods of prevention.
AB  - Drug-food interactions in hospitalised patients may result in decreased drug
      efficacy or increased drug toxicity. The increasing complexity of drug therapy
      regimens has increased the potential for drug-food interactions to occur,
      reinforcing the need to develop methods to prevent clinically significant drug
      food interactions. Before selecting the optimal method, in terms of feasibility
      of implementation and successful outcome, drugs with the potential for clinically
      significant interactions with food must be identified. From an analysis of the
      literature, 6 methods to prevent drug-food interactions have been suggested as
      useful tools. Each method has its own advantages and disadvantages. Most have
      been developed in response to guidelines from the most well recognised agency for
      quality review in the US, the Joint Commission on Accreditation of Healthcare
      Organisations (JCAHO). Based on those recommendations, an ideal programme to
      prevent drug-food interactions would be a combined patient counselling and label
      system to select the most appropriate drug administration times and increase
      nurse and patient awareness of the potential for drug-food interactions. However,
      because of time constraints and limited resources, a label system or the
      provision of a drug-food interaction pamphlet to the patient before discharge
      would be a more practical method. Newsletters and educational in-services
      combined with patient counselling or a label system would be a valuable method to
      prevent drug-food interactions in hospitalised patients.

PMID- 9638386
TI  - A risk-benefit assessment of irinotecan in solid tumours.
AB  - Irinotecan is a water-soluble camptothecin analogue. Its cytotoxicity effects are
      exerted through interaction with the topoisomerase I-DNA complex, eventually
      leading to cell death. In preclinical studies, irinotecan has demonstrated a
      broad spectrum of activity in vitro and in vivo, and synergistic effects have
      been observed when it is administered in combination with other antineoplastic
      agents. Phase I studies of irinotecan conducted in Europe, Japan and the US have
      provided useful information on optimal dosage and scheduling, as well as thorough
      evaluation of the toxicity profile of the drug. Phase II and III trials utilising
      either irinotecan alone or in innovative combinations with other drugs are
      currently in progress. Available data indicate that irinotecan alone or in
      combination with other cytotoxic agents has therapeutic potential in several
      types of malignancy, including colorectal, lung, ovarian, cervical and gastric
      cancers and non-Hodgkin's lymphoma. It is the first drug since fluorouracil to
      possess consistent antitumour activity against metastatic colorectal cancer. The
      principal toxicities associated with irinotecan are diarrhoea and leucopenia.
      Effective strategies have been developed to circumvent both the early- and
      delayed-onset diarrhoea induced by irinotecan, thus allowing safer delivery of
      this promising agent in the clinical setting.

PMID- 9638387
TI  - A risk-benefit assessment of pharmacological treatments for panic disorder.
AB  - Panic disorder, a psychiatric disorder characterised by frequent panic attacks,
      is the most common anxiety disorder, affecting 2 to 6% of the general population.
      No one line of treatment has been found to be superior, making a risk-benefit
      assessment of the treatments available useful for treating patients. Choice of
      treatment depends on a number of issues, including the adverse effect profile,
      efficacy and the presence of concomitant syndromes. Tricyclic antidepressants
      (TCAs) are beneficial in the treatment of panic disorder. They have a proven
      efficacy, are affordable and are conveniently administered. Adverse effects,
      including jitteriness syndrome, bodyweight gain, anticholinergic effects and
      orthostatic hypotension are commonly associated with TCAs, but can be managed
      successfully. Selective serotonin (5-hydroxytryptamine; 5HT) reuptake inhibitors
      are also potential first line agents and are well tolerated and effective, with a
      favourable adverse effects profile. There is little risk in overdose or of
      anticholinergic effects. Adverse effects include sedation, dyspepsia and headache
      early in treatment, and sexual dysfunction and increased anxiety, but these can
      be effectively managed with proper dosage escalation and management.
      Benzodiazepines are an effective treatment, providing short-term relief of panic
      related symptoms. Patients respond to treatment quickly, providing rapid relief
      of symptoms. Adverse effects include ataxia and drowsiness, and cognitive and
      psycho-motor impairment. There are reservations over their first-line use because
      of concerns regarding abuse and dependence. Monoamine oxidase inhibitors, because
      of their adverse effects profile, potential drug interactions, dietary
      restrictions, gradual onset of effect and overdose risk, are not considered to be
      first-line agents. They are effective however, and should be considered for
      patients with refractory disease. Valproic acid (valproate sodium), while not
      intensively studied, shows potential for use in panic disorder. More studies are
      needed in this area before the available data can be confirmed. As a supplement
      to drug therapy, cognitive behavioural therapy is effective. It is well
      tolerated, and may be beneficial in certain clinical situations. Its main
      drawback is the time commitment and effort needed to be made by the patient.

PMID- 9638388
TI  - Minocycline-induced pigmentation. Incidence, prevention and management.
AB  - Pigmentation is a well recognised adverse effect of minocycline therapy. Various
      body sites, most notably the skin, nails, bones, thyroid, mouth and eyes are
      affected and the pigmentation may appear at multiple sites. In general,
      pigmentation results from long term administration of minocycline at cumulative
      doses greater than 100 g, although cutaneous or oral mucosal pigmentation may
      appear, regardless of dose or duration of therapy. When the skin is involved, the
      blue-black pigmentation develops most frequently on the shins, ankles and arms.
      Other patterns of skin involvement include pigmentation that is either
      generalised and symmetrical, or that develops at sites of inflammation. The bones
      of the oral cavity are probably the most frequently affected sites of
      pigmentation affecting greater than 20% of patients taking minocycline for more
      than 4 years. In contrast, the oral mucous membranes and teeth are infrequently
      pigmented from minocycline. Ocular, thyroid and visceral pigmentation is also
      relatively uncommon and usually develops only with high doses and long term
      minocycline use. Whereas pigmentation of the skin and oral mucosa is generally
      reversible when the drug is discontinued, the pigmentation is often permanent
      when other sites are involved. Although minocycline-induced pigmentation is not
      harmful, the drug should be discontinued when the adverse effect is recognised.
      All patients receiving minocycline, especially those treated for longer than 1
      year, require screening for the development of pigmentation.

PMID- 9638389
TI  - Drug administration in patients with diabetes mellitus. Safety considerations.
AB  - Diabetes mellitus is associated with alterations in a number of key metabolic
      pathways. Despite theoretical concerns, clinically significant alterations in the
      pharmacokinetic properties of commonly prescribed drugs are relatively uncommon.
      Indeed, dose adjustment is rarely required in the setting of well controlled
      diabetes mellitus. However, significant alterations in drug handling may occur in
      the context of poor metabolic control or in the presence of complications such as
      nephropathy. Metformin use may be complicated by lactic acidosis. Fortunately,
      this is a rare occurrence providing that the agent is not used in circumstances
      in which it is contraindicated. Indeed, the risk of death from metformin-related
      lactic acidosis is similar in magnitude to the risk of death related to
      hypoglycaemia in sulphonylurea-treated patients. The novel hypoglycaemic agent
      troglitazone may be associated with abnormalities in liver function in
      approximately 2% of patients. Discontinuation of treatment is followed by
      normalisation of liver enzyme levels. Current prescribing information recommends
      frequent monitoring of liver function tests and immediate cessation of therapy if
      abnormalities develop. In addition to disturbances in intermediary metabolism,
      diabetes mellitus may also lead to chronic microvascular and marcovascular
      complications. Thus, in addition to the use of drugs for the control of blood
      glucose, patients with diabetes mellitus are likely to be prescribed medication
      for associated conditions such as cardiovascular disease. Such medication
      includes the ACE inhibitors which are contraindicated in patients with bilateral
      renal artery stenosis. This complication may be theoretically more common in
      patients with diabetes mellitus because of accelerated atherosclerosis. However,
      in clinical practice this is an uncommon occurrence in the absence of clinical
      features that should alert the treating clinician that an individual patient
      might be at high risk. Although caution should also be used with beta-blocker
      therapy in patients with diabetes mellitus, current evidence suggests that, like
      ACE inhibitors, these drugs may be particularly useful in this patient group.

PMID- 9638391
TI  - The ELITE Study. What are its implications for the drug treatment of heart
      failure? Evaluation of Losartan in the Elderly Study.
AB  - Angiotensin II type 1 (AT1) receptor antagonists inhibit the renin-angiotensin
      system more completely than ACE inhibitors, and do not increase bradykinin levels
      as ACE inhibitors do. ACE inhibitors have been proven to increase survival and
      improve quality of life in patients with congestive heart failure (CHF). At the
      48-week follow-up of the Evaluation of Losartan in the Elderly (ELITE) Study, the
      AT1 receptor antagonist losartan (at a dosage of 50 mg/day) was found to be
      superior to captopril 50 mg 3 times daily in terms of its effects on total
      mortality, total mortality and/or hospitalisation for CHF, and hospitalisation
      for any reason. Hospitalisation for CHF was the same for both drugs. Adverse
      effects occurred in 12 and 21% of those receiving losartan and captopril,
      respectively. Cough, rash, angioedema or taste disturbances/reduced appetite
      prompted the cessation of drug treatment in 0 and 7% of those receiving losartan
      and captopril, respectively. Until additional data are available, this author
      recommends that elderly patients with CHF and an abnormal or normal left
      ventricular ejection fraction, and who are unable to tolerate ACE inhibitors,
      should receive losartan 50 mg/day.

PMID- 9638390
TI  - Pain treatment in multimorbid patients, the older population and other high-risk
      groups. The clinical challenge of reducing toxicity.
AB  - The prevalence of pain is high in multimorbid patients and they can experience a
      multitude of painful conditions. The changes in physiology and homeostasis
      associated with multimorbidity and increasing age and the immature metabolism of
      neonates all increase the risk of toxicity from analgesics. Altered
      pharmacokinetics and metabolism influence drug pharmacodynamics and therapeutic
      windows. Imbalances in local homeostatic mechanisms increase local toxicity. The
      gastrointestinal organs and the kidney have a major role in the absorption,
      metabolism and excretion of analgesics and changes in their function predispose
      individuals to adverse effects. Knowledge of such compromise should influence the
      choice of analgesic, the administration regimen and the mode of application. The
      mainstay of chronic pain treatment are 3 classes of drugs: nonsteroidal anti
      inflammatory drugs (NSAIDs), opioids and a host of so-called adjuvant drugs,
      which are used to enhance the analgesic action of the classic analgesics. In each
      class a wide range of drugs are available, that differ in pharmacokinetic and
      pharmacodynamic characteristics. These differences can be exploited to either
      increase analgesic efficacy and reduce toxicity, or to minimise the interference
      of pain therapy with daily life. Clinically important differences in analgesic
      and toxic effects between drugs in each analgesic class will be discussed in this
      article from the perspective of reducing adverse effects. New knowledge
      concerning the mechanism of action of analgesics and their metabolites is making
      the specific selection of NSAIDs and opioids to reduce adverse effects in
      multimorbid, chronic pain patients possible.

PMID- 9638392
TI  - Alpha 1-antitrypsin. Hope on the horizon for emphysema sufferers?
AB  - Alpha 1-Antitrypsin (alpha 1AT) deficiency is the most common genetic cause of
      liver disease in children and emphysema in adults. Therapy for pulmonary disease
      attributable to alpha 1AT deficiency includes alpha 1AT augmentation therapy
      along with supportive measures. The alpha 1AT preparation that is currently used
      for therapy is derived from fractionated plasma. The results of clinical trials
      suggest that augmentation therapy with alpha 1AT slows the progression of
      emphysema and causes few adverse events. Patients with plasma levels of alpha 1AT
      that are < 11 mumol/L and who have airway obstruction should be considered for
      augmentation therapy. Novel approaches include the administration of aerosolised
      alpha 1AT, recombinant alpha 1AT, gene therapy and synthetic elastase inhibitors.

PMID- 9638393
TI  - Drug therapy in haemodialysis patients. Special considerations in the elderly.
AB  - End-stage renal disease (ESRD) is the stage of renal failure at which an
      individual requires dialysis therapy or a renal transplant to survive. The
      prevalence of ESRD is disproportionately higher among patients aged > 65 years,
      and the average age of new ESRD patients is continually rising in the US Medicare
      population. Medication management in this population is challenging because of
      the combination of multiple comorbid disease states, a plethora of medications
      and the added dimension of dialysis therapy, as well as pharmacokinetic and
      pharmacodynamic changes attributable to the aging process. Cardiovascular
      disorders such as hypertension, coronary artery disease, congestive heart failure
      and arrhythmias are common in elderly patients with ESRD, and account for most of
      the deaths in this population. Constipation is common in patients aged > 65
      years, and its incidence is even higher among those receiving dialysis. Pain
      management is of particular concern because elderly dialysis patients are
      frequently prescribed inappropriate pain relief regimens. Many healthcare
      practitioners do not realise that patients with uraemia are at a higher risk of
      bleeding caused by nonsteroidal anti-inflammatory drugs than are patients with
      normal renal function. In addition, most practitioners do not appreciate that
      virtually all opioids (narcotics) and their active metabolites accumulate in
      patients with renal failure, leading to an increased risk of narcosis. Infectious
      complications are frequent in the ESRD population, with dialysis access
      infections and pneumonia being the 2 most common infections seen in hospitalized
      patients receiving dialysis treatment. The establishment of vaccination
      programmes for the prevention of hepatitis B, influenza and pneumococcal
      infections is important because of the increased risk of these disease in this
      population. Unfortunately, these high-risk patients display, in general, a
      decreased immunogenic response to vaccinations. This article addresses some of
      the practical issues that surround the medication management or prevention of
      these particular diseases in elderly patients undergoing haemodialysis.
      Specifically, we discuss the pharmacokinetic and pharmacodynamic changes that
      occur with specific medications in such patients. Drug dialysability is also
      discussed.

PMID- 9638394
TI  - The use of drugs for cardioversion of recent onset atrial fibrillation and
      flutter. Focus on ibutilide.
AB  - Atrial fibrillation (AF) is the most common sustained arrhythmia, particularly in
      the elderly population. It is well recognised that AF is a major cause of stroke,
      even in the absence of underlying heart disease. Although AF and atrial flutter
      share many causes and may be seen in the same patient, there are differences
      between these arrhythmias: atrial flutter is less common, and the risk of stroke
      associated with it is less than that with AF. In addition to stroke, both AF and
      atrial flutter may cause cardiomyopathy, which may be fully reversible with
      effective treatment of the arrhythmia. Both AF and atrial flutter can result in
      severe symptoms and may precipitate heart failure, ischaemia and syncope. Recent
      research indicates that AF is a self-perpetuating arrhythmia, and that the longer
      it is left untreated the less likely it is that effective cardioversion will be
      possible. Drugs are an attractive option for the cardioversion of AF and atrial
      flutter because their use does not require anaesthesia. Antiarrhythmic drugs in
      class III of the Vaughan-Williams classification are effective in the treatment
      of AF, but they have adverse effects; several new 'pure' class III agents are
      under development. The first of these to be made available is ibutilide, a
      methanesulphonamide derivative. Initial results are encouraging, particularly for
      atrial flutter. However, the drug has the potential for proarrhythmic effects and
      physicians who use it will need to be aware of these.

PMID- 9638395
TI  - Pathogenesis and treatment of glucocorticoid-induced osteoporosis.
AB  - Aging is associated with a marked decline in bone mineral density (BMD), an
      increased likelihood of falling and a much greater propensity for fracture.
      Several factors contribute to aging-related bone loss, including reduced bone
      formation, increased bone resorption, recent bodyweight loss, poor nutritional
      status and the coexistence of other, often rheumatological, conditions. Any of
      these factors can lead to an uncoupling of the bone remodelling unit. In
      addition, the frequent use of glucocorticoids to treat a vast array of conditions
      has contributed to an ever-expanding group of elderly individuals who are at
      extremely high risk for spine and hip fractures. Owing to the surprisingly high
      morbidity and mortality associated with these fractures in the elderly, an
      understanding of the pathogenesis and epidemiology of glucocorticoid-induced
      osteoporosis is paramount. The factors that contribute to bone loss in older
      individuals treated with glucocorticoids include reduced muscle mass, poor
      nutrition, hypogonadism, vitamin D deficiency and secondary hyperparathyroidism.
      Recent studies suggest that a prophylactic approach to this problem could have a
      huge impact on the medical, social and economic costs of osteoporosis.

PMID- 9638396
TI  - Important drug-drug interactions in the elderly.
AB  - Although drug-drug interactions constitute only a small proportion of adverse
      drug reactions, they are important because they are often predictable and
      therefore avoidable or manageable. Their frequency is related to the age of the
      patient, the number of drugs prescribed, the number of physicians involved in the
      patient's care and the presence of increasing frailty. The most important
      mechanisms for drug-drug interactions are the inhibition or induction of drug
      metabolism, and pharmacodynamic potentiation or antagonism. Interactions
      involving a loss of action of one of the drugs are at least as frequent as those
      involving an increased effect. It is likely that only about 10% of potential
      interactions result in clinically significant events and, while death or serious
      clinical consequences are rare, low-grade, clinically unspectacular morbidity in
      the elderly may be much more common. Nonspecific complaints (e.g. confusion,
      lethargy, weakness, dizziness, incontinence, depression, falling) should all
      prompt a closer look at the patient's drug list. There are a number of strategies
      that can be adopted to decrease the risk of potential clinical problems. The
      number of drugs prescribed for each individual should be limited to as few as is
      necessary. The use of drugs should be reviewed regularly and unnecessary agents
      withdrawn if possible, with subsequent monitoring. Patients should be encouraged
      to engage in a 'prescribing partnership' by alerting physicians, pharmacists and
      other healthcare professionals to symptoms that occur when new drugs are
      introduced. Physicians with a responsibility for elderly people in an
      institutional setting should develop a strategy for monitoring their drug
      treatment. For those interactions that have come to clinical attention, it is
      important to review why they happened and to plan for future prevention.
      Clinicians should also report, via the appropriate postmarketing surveillance
      scheme, any drug-drug interactions they have encountered. Finally,
      multidisciplinary education about the nature of physiological aging and its
      effect on drug handling, and the possible presentations of drug-related disease
      in older patients, is an important element in reducing interactions in the
      elderly.

PMID- 9638398
TI  - Current and future therapies for HCV infection: what should the end point for
      treatment be?
AB  - Based upon all of the available data relating to the natural history, chemical
      course, and response to therapy of HCV, the following recommendations are made:
      1) The primary end point for HCV therapy should be HCV clearance from all tissue
      sites, eg plasma, liver and others 2) Therapy should be provided for patients
      with early infections as they have the best chance of achieving a virologic
      response 3) Therapy should be offered to patients with cirrhotic disease, as
      prevention of hepatic decompensation and degeneration to hepatic cancer is
      possible 4) End stage decompensated disease should be treated, particularly if
      liver transplantation is being considered, in an effort to either eliminate or
      ameliorate disease recurrence 5) Combination therapies are preferable to
      monotherapy as they enhance the likelihood of a therapeutic response. Some of
      these include agents that reduce the frequency of IFN-induced untoward events
      (NSAIDs) 6) The approach to HCV infection should be to view it as an infectious
      disease. In this way, multi-agent therapy could be used to prevent the emergence
      of drug resistant mutants as well as to obtain earlier clearance of the infection
      than is possible with monotherapy.

PMID- 9638397
TI  - Pramipexole. A review of its use in the management of early and advanced
      Parkinson's disease.
AB  - Pramipexole is an orally active non-ergoline dopamine agonist with selective
      activity at dopamine receptors belonging to the D2 receptor subfamily (D2, D3, D4
      receptor subtypes) and with preferential affinity for the D3 receptor subtype. It
      is approved as monotherapy in early Parkinson's disease and as adjunctive therapy
      to levodopa in patients with advanced disease experiencing motor effects because
      of diminished response to levodopa. The potential neuroprotective effects of
      pramipexole have been shown in animal and in vitro studies. Data from relatively
      long term (10- or 31-week) studies suggest that pramipexole monotherapy (0.375 to
      6.0 mg/day) can improve activities of daily living and motor symptoms in patients
      with early Parkinson's disease. Pramipexole (0.375 to 4.5 mg/day for 31 or 36
      weeks), as an adjunct to levodopa in advanced disease, improved activities of
      daily living and motor symptoms, reduced the duration and severity of 'off'
      periods and allowed a reduction in levodopa dosage. Mentation, behaviour and mood
      [Unified Parkinson's Disease Rating Scale (UPDRS) part I], and timed walking test
      were not significantly improved. The extent of disability improved according to
      the UPDRS parts II and III but, when assessed by secondary efficacy parameters,
      it is unclear whether disability or the severity of disease improved. No
      significant differences were observed in patients randomised to pramipexole or
      bromocriptine according to a secondary hypothesis in a prospective study in which
      both drugs were better than placebo. Some quality-of-life measures improved with
      active treatment relative to placebo. Further studies comparing pramipexole with
      other dopamine agonists and levodopa in patients with early and advanced
      Parkinson's disease would be useful. In pramipexole recipients with early
      disease, the most commonly experienced adverse events were nausea, dizziness,
      somnolence, insomnia, constipation, asthenia and hallucinations. The most
      commonly reported adverse events in pramipexole recipients with advanced disease
      were orthostatic hypotension, dyskinesias, extrapyramidal syndrome (defined as a
      worsening of the Parkinson's disease), dizziness, hallucinations, accidental
      injury, dream abnormalities, confusion, constipation, asthenia, somnolence,
      dystonia, gait abnormality, hypertonia, dry mouth, amnesia and urinary frequency.
      The incidence of some adverse events did not greatly differ between pramipexole
      and placebo recipients. CONCLUSIONS: Pramipexole is effective as adjunctive
      therapy to levodopa in patients with advanced Parkinson's disease. However, the
      potential beneficial effects of pramipexole on disease progression need to be
      confirmed in clinical studies. The efficacy of pramipexole monotherapy in
      patients with early disease has also been demonstrated, although the use of
      dopamine agonists in early Parkinson's disease remains controversial.

PMID- 9638399
TI  - Treatment of HCV positive individuals with normal serum ALT levels.
AB  - A substantial number of cases of chronic hepatitis C infection can be shown to
      have normal or near normal serum ALT levels. Major questions that arise when such
      cases are seen are: should such patients be treated; if so for how long; and what
      is the end point of therapy. The reported experience of such patients treated by
      IFN is reviewed.

PMID- 9638400
TI  - Use of interferon for the treatment of chronic hepatitis C in the elderly.
AB  - Hepatitis C virus is a worldwide health care problem. It affects all age groups.
      Many patients have had the infection for 20-30 years before they present for
      therapy. With a peak incidence of disease in the 30-40 year age group, it is
      obvious that a large number of cases must occur in the elderly (age > 65 years).
      Of these, a fraction progress to cirrhosis and hepatocellular carcinoma.
      Interferon is the only agent approved for use in patients with chronic hepatitis
      C. The efficacy of interferon in younger patients is reported to be 50%. Half of
      these will experience a relapse within 1 year. There are few studies assessing
      the role of interferon used for elderly patients with chronic hepatitis C. The
      reported response rate to interferon in elderly patients was 60%, with 30% having
      a virologic/complete response. These studies demonstrate that the elderly
      tolerate interferon reasonably well. No significant differences have been
      reported between elderly and young treatment groups.

PMID- 9638401
TI  - Treatment of chronic hepatitis C in individuals with pre-existing or confounding
      neuropsychiatric disease.
AB  - The problems associated with the recognition and management of chronic hepatitis
      C in a population of individuals with confounding psychiatric disease are
      identified. The experience of treating such patients and the psychotropic
      medication required during treatment are reviewed.

PMID- 9638402
TI  - The interaction of alcoholic liver disease and hepatitis C.
AB  - The following article reviews available data of the interaction of alcohol
      related liver disease and hepatitis C viral infection as well as special
      considerations for the treatment of these patients. Alcohol worsens the degree
      and accelerates the progression of hepatic injury, enhances the risk of
      developing hepatocellular carcinoma and decreases response to interferon therapy.
      Patients with hepatitis C should avoid alcohol ingestion.

PMID- 9638403
TI  - Interferon treatment of HCV positive cirrhotic patients.
AB  - An estimated 3.5 million people in the United States have chronic hepatitis C.
      Each year, 8,000 to 10,000 of these chronically infected patients die of a liver
      related complication of their infection. The introduction of effective blood
      screening assays has resulted in a remarkable decrease in the incidence of post
      transfusion HCV infection. Nonetheless, hepatitis C remains an important clinical
      problem. Some important new treatment programs can help prevent the development
      and progression of compensated cirrhosis to either decompensated cirrhosis or
      HCC. Patients who present to the health care system with advanced chronic active
      hepatitis or cirrhosis have been treated with interferon. Of those studied, only
      IFN therapy has been shown to induce remissions of the hepatic inflammatory
      process and to eliminate viral infection in most treated cases. However, it is
      widely held assumption that cirrhotic individuals do not respond to IFN therapy
      and that the treatment of decompensated cirrhotic individuals with HCV infection
      is dangerous. We believe that this assumption is false. In many studies,
      cirrhotic patients with chronic hepatitis C have been shown to respond to IFN
      therapy. However, they do so at a rate of half that reported for individuals with
      non-cirrhotic chronic active hepatitis. There have been no reports of hepatic
      decompensation as a consequence of IFN treatment of cirrhotic individuals with
      chronic hepatitis C. The use of IFN for cirrhotic patients is reviewed.

PMID- 9638404
TI  - Interferon treatment of children with chronic hepatitis C.
AB  - Hepatitis C virus (HCV) is the major cause of acquired non-A, non-B hepatitis.
      Interferon is becoming the standard treatment in adults for chronic hepatitis C,
      however, the experience with interferon treatment in children is very limited.
      The review article describes the current approach in the management of children
      with chronic hepatitis C infection and the review of the literatures.

PMID- 9638405
TI  - Role of iron in the natural history and clinical course of hepatitis C disease.
AB  - The following review evaluates the current data implicating a role for hepatic
      iron in enhancing the liver injury in patients with chronic hepatitis C
      infection. Iron removal lowers transaminases, but doesn't appear to improve
      responsiveness to interferon-alpha therapy. An important effect of iron removal
      might be to delay progression of liver injury to fibrosis and cirrhosis. Until
      such a hypothesis is disproven, phlebotomy therapy for even mildly iron-loaded
      HCV patients is recommended.

PMID- 9638406
TI  - Biology, physiology and physiopathology of clamping during liver surgery.
AB  - Liver surgery is currently performed with minimal morbidity and mortality, mostly
      thanks to reduced intraoperative blood loss, achievable by various types of liver
      clamping. A better knowledge of the physiological and physiopathological changes
      caused by liver clamping is however still necessary. The "natural" evolution of
      biochemical and liver function tests after liver surgery have been described.
      This paper describes the hemodynamic changes observed with different types of
      clamping and discusses several ways in which liver clamping techniques might be
      improved.

PMID- 9638407
TI  - Major liver resections without vascular clamping: retrospective study of 84
      cases.
AB  - BACKGROUND/AIMS: The question as to whether vascular clamping aggravates
      mortality and morbidity of major liver resection was investigated in this study.
      Major liver resection with vascular clamping for parenchyma transection has
      mortality between 0 and 5%, and higher morbidity reaching 47% with healthy liver
      in recent report. METHODOLOGY: Eighty-four major liver resection without vascular
      clamping were carried out between January 1986 to December 1996 were reviewed.
      There were 57 men and 27 women with average age of 58.2 (12.2) years old.
      Indications of resection were adenoma (4.8%) angioma (11.9%) focal nodular
      hyperplasia (1.2%) hematoma (1.2%) metastases (60.7%) hepatocellular carcinoma
      (14.3%) and cholangiocarcinoma (5.9%). Resections used ultrasonic dissector
      (Sonoca) with intraoperative ultrasonography were right hepatectomy in 56 cases
      extended right hepatectomy in 10 cases left hepatectomy in 17 cases and middle
      hepatectomy in 1 case. Remnant liver was cirrhotic in 3 cases. RESULTS: Three
      patients died (3.5%) and the rate of major complications were 11.2%. 46 patients
      (54.8%) had no blood transfusion. The mean of blood transfusion was 1.5 (2.7)
      units. The mean of operative length was 286.23 (63.3) minutes and the mean
      hospital stay was 15.8 (8.1) days. Liver function tests are same with the others
      authors at day 1, 4 and 7 after operation with return to normal value after 1
      week. CONCLUSION: In major liver resection, vascular clamping is not always
      necessary.

PMID- 9638408
TI  - Total vascular exclusion for liver resection.

PMID- 9638409
TI  - Routine use of total hepatic vascular exclusion in major hepatectomy is not
      necessary.
AB  - The prime concert of a hepato-biliary surgeon undertaking liver resection is to
      minimise blood loss and prevent air embolism through the control of the major
      vascular structures. Several methods to achieve this are now available and
      include in particular clamping of the hepatic pedicle and total vascular
      exclusion. Both techniques are detailed as well as their benefits and drawbacks.
      For conventional liver resections, total vascular exclusion has no advantage over
      clamping of the hepatic pedicle in preventing blood loss and is associated with
      additional morbidity. This technique should be selectively used in patients with
      tumours involving major hepatic veins or the inferior vena cava.

PMID- 9638410
TI  - Selective and unselective clamping in cirrhotic liver.
AB  - BACKGROUND/AIMS: Liver surgery requires a reduction of the operative blood loss
      especially for patients with cirrhosis. Selective or unselective liver clamping
      during hepatic resection is performed to minimize the surgical risk for such
      compromised patients. METHODOLOGY: We carried out elective hepatic resection in
      158 patients with the use of total hilar clamping (Pringle's manoeuvre) or
      selective vascular clamping (Makuuchi's manoeuvre). The clinical outcomes were
      evaluated according to the clamping method and the condition of background liver.
      RESULTS: Pringle's manoeuvre was used in 132 patients who underwent all types of
      hepatectomy, whereas Makuuchi's manoeuvre was applied selectively to 26 patients,
      most of whom underwent segmentectomy or subsegmentectomy. A modified Makuuchi's
      manoeuvre was used in eight healthy donors who underwent left-sided hepatectomy
      for transplantation. The cumulative clamping times and blood losses were 61 +/-
      47 min (mean +/- SD) and 831 +/- 716 ml in the Pringle's manoeuvre group, and 95
      +/- 47 min and 1.035 +/- 577 ml in the Makuuchi's manoeuvre group. In patients
      with normal hepatic parenchyma the longest clamping time was 322 min, and in
      those with cirrhosis it was 202 min. All the patients in this series tolerated
      vascular clamping well, and their hepatic functional parameters returned,
      regardless of the presence or absence of cirrhosis, to the baseline levels within
      a week. As a whole, the operative morbidity and mortality rates were 20.3% and
      0%, respectively. CONCLUSIONS: Intermittent total or selective clamping can be an
      indispensable procedure during hepatic resection for all patients, irrespective
      of the degree of hepatic dysfunction, to improve safety and resectability.

PMID- 9638411
TI  - Hepatectomy with hypothermic perfusion of the liver.
AB  - Whereas most liver resections can be performed within 60 min, the period of
      vascular clamping and resulting ischemia may prove too short to allow complex
      major liver resections (MLR) especially on diseased livers. To overcome this
      problem, cooling of the liver with 4 degrees C preservations solution routinely
      used in liver transplantation may be used in three different approaches to MLR: I
      "In situ": the liver remains in the abdomen and integrity of afferent and
      efferent vessels is conserved. II "Ex situ-in vivo": the liver exteriorized from
      the abdomen by transecting all hepatic veins, remains connected to the porta
      hepatis. III "Ex vivo": the liver being removed from the abdomen, the MLR is
      performed extracorporeally. Of 15 MLR reported here, 11 were performed "in situ"
      and 4 "ex situ-in vivo"/Nowadays, the liver surgeon's "toolbox" must contain
      hypothermic liver perfusion. In carefully selected cases, these techniques allow
      MLR on diseases livers or mandating complex vascular procedures.

PMID- 9638412
TI  - Intermittent complete vascular exclusion of the liver during hepatectomy:
      technique and indications.
AB  - BACKGROUND/AIMS: Complete intermittent vascular exclusion of the liver (IVEL)
      combines clamping of the hepatic pedicle with clamping of the hepatic veins
      without interruption of the caval flow. The major advantages of this technique
      are that patient preclamping fluid overload is avoided, major haemodynamic
      changes due to caval clamping are escaped, and it allows a very long clamping
      time. Disadvantage of this technique is the necessity of looping the terminal
      part of the hepatic veins. METHODOLOGY: In this prospective study, 41 cases of
      IVEL (Representing 19% of the hepatectomies carried out for cancer during the
      same period) used for difficult hepatectomies were analyzed, and the operative
      technique is presented. RESULTS: IVEL was feasible in 90% of the 46 attempted
      cases, and completely controlled the bleeding in 90% of the cases. The mean
      duration of IVEL was 69.2 minutes (Range: 37 to 140), and was greater than 130
      minutes in three patients. No liver failure occurred during the postoperative
      course. CONCLUSION: We conclude that IVEL without caval clamping is a new, and
      valuable, technique of vascular exclusion of the liver. Its application is
      indicated in the following conditions: 1. For patients who should have classical
      vascular exclusion but cannot tolerate vena cava clamping (18% of the cases), 2.
      for patients with pathological liver parenchyma when intrahepatic venous pressure
      is high, 3. for patients with impaired liver parenchyma, requiring conservative
      surgery that leads to anatomic or non-anatomic resection close to a vein
      (Example: A tumor located in the dihedral angle of the terminal part of two
      hepatic veins), 4. for patients with tumors closely located to a hepatic vein
      that must be preserved and sharply dissected (Example: A left trisegmentectomy
      that requires pelting of the right hepatic vein), and 5. for the scarce patient
      with tumors infiltrating the major hepatic veins, constraining a hepatic vein
      reconstruction to preserve liver function.

PMID- 9638413
TI  - Pancreatic resection for pancreatic carcinoma combined with neo- and adjuvant
      locoregional targeting immuno-chemotherapy--a prospective randomized study.
AB  - BACKGROUND/AIMS: The effects on early and late results of combined pancreatic
      resection with neo- and adjuvant immuno-chemotherapy for patients undergoing
      pancreatic resection are prospectively evaluated. METHODOLOGY: A group of 26
      patients was divided into two groups, which were matched in terms of age-sex
      ratio, stage of disease, histological diagnosis and mode of pancreatic resection.
      Group A patients received a multimodality therapy, combining pancreatic resection
      with neo- and adjuvant locoregional targeting immunochemotherapy. Group B
      received pancreatic surgery only. RESULTS: For Group A patients (n = 14pts), a
      complete response was seen in 11 patients with a time interval ranging from 9 to
      29 months. In the remaining 3 patients liver secondaries developed 12 months
      after pancreatic resection in 2 patients and the other patient developed
      pulmonary metastases 22 months after pancreatic resection. All patients (n =
      3pts) are alive, but continue to have the disease. For Group B patients (n =
      12pts), a complete response was seen in 3 patients with a survival of 9, 10 and
      20 months following pancreatic resection. Six patients died due to locoregional
      recurrence of the disease, with the survival rate ranging from 7 to 18 months
      (mean 10 months). Locoregional recurrence was complicated with liver secondaries
      (n = 3) and with peritoneal dissemination of the disease in a further 3 patients.
      The remaining 3 patients are alive, but continue to have the disease due to
      locoregional recurrence. CONCLUSIONS: Patients in whom neo- and adjuvant
      locoregional immunochemotherapy was carried out in conjunction with pancreatic
      resection, demonstrated a significantly higher response rate to treatment.
      Therefore the data collected offers clear evidence, regarding the usefulness,
      applicability and safety of combined neo- and adjuvant therapy with pancreatic
      resection. A Multi-modality approach is therefore highly recommended.

PMID- 9638414
TI  - Intrasplenic immunostimulation in malignancies fact or fiction? Present and
      future.
AB  - BACKGROUND/AIMS: The clinical application of intrasplenic immunostimulation with
      IL-2 in a group of patients suffering from metastatic renal carcinoma, melanoma,
      recurrent rectal carcinoma, lung carcinoma and gastric carcinoma are discussed in
      terms of clinical applicability, effectiveness and survival. METHODOLOGY: From
      May 1996 to February 1998, 45 patients with advanced malignancies were admitted
      to Athens Medical Center for intrasplenic immunostimulation. Transplenic
      immunostimulation was carried out via a subcutaneously implanted port. The
      injected therapy included IL-2 (Proleukin) 1 ml 18 x 10(6) suspended in 1.5 ml of
      lipiodol and 0.5 ml of urografin. In conjunction gamma-INF (Immukin) 0.5 ml 100
      mcg, was administered. RESULTS: Patients included in this study have completed
      their treatment, or are still undergoing maintenance treatment. The duration of
      the CR was between 11 and 16 months, and for PR was between 10-14 months. For
      melanoma patients (n = 9), 3 patients with PD died 9, 10 and 12 months after
      initial treatment began. The remaining patients (n = 6) are alive with a mean
      survival rate of 16 months. Of those patients, 4 have been classified as complete
      responders, being completely free of disease at this time. The number of CR for
      patients with lung, renal and recurrent rectal cancer was achieved as a result of
      the continuing maintenance treatment. Twenty-two patients remain alive and 23
      patients have died. From those alive (n = 22), 10 patients are complete
      responders and free of disease, 10 are partial responders with controlled disease
      and 2 remain with standard disease. For those surviving patients with lung
      cancer, the mean survival time is 14 months. Patients with recurrent rectal
      cancer and renal cancer were shown to have a mean survival time of 15 and 13
      months, respectively. CONCLUSION: The safety, effectiveness and feasibility of
      long-lasting administration of high dosages of IL-2 are documented from the data
      of this study. Intrasplenic immunostimulation utilizing lipiodol-urografin
      emulsion as a carrier, offers new possibilities for the safe administration of
      long lasting high dosages of IL-2 and gamma-INF. Further studies are warranted,
      to further elucidate the results of this phenomenon.

PMID- 9638415
TI  - Diphenylhydantoin-induced hepatitis: a case report.
AB  - This case report is of a 25-year old man with severe diphenylhydantoin-induced
      hepatitis, fever, rash and generalized lymphadenopathy. Hepatic histology and
      lymphocyte transformation tests strongly supported the diagnosis. He made an
      uneventful recovery with supportive therapy.

PMID- 9638416
TI  - Endoscopic irradiation and parallel arrangement of Wallstents for hilar
      cholangiocarcinoma.
AB  - BACKGROUND/AIMS: The placement of two Wallstents in parallel seems to be a common
      solution for endoscopic technique in order to obtain bilateral hepatic drainage
      in patients with hilar biliary strictures. However, a biliary stricture at the
      hepatic confluence hinders the sequential delivery of multiple Wallstents.
      Intraductal irradiation has been shown to recanalize the cancerous stricture
      caused by cholangiocarcinoma. METHODOLOGY: We attempted to place two Wallstents
      in parallel by endoscopic means after endoscopic intraductal irradiation with a
      high-dose rate afterloading device in three patients with hilar
      cholangiocarcinoma. After the placement of two guidewires into the bilateral
      hepatic ducts, two Wallstents were sequentially delivered over the guidewires.
      RESULTS: Owing to adequate re-opening of the hilar bile ducts after irradiation,
      the delivery of the second Wallstent alongside the expanded first Wallstent could
      be readily accomplished in all of the patients without complications. Two
      Wallstents were placed so that their distal ends were juxtaposed in the common
      bile duct, ensuring good drainage. There were no signs of recurrent biliary
      obstruction in any of the patients during the follow-up period of 24 to 44 weeks.
      CONCLUSION: This endoscopic technique seems to be simple, safe, and reliable in
      obtaining bilateral hepatic drainage with Wallstents in patients with hilar
      cholangiocarcinoma.

PMID- 9638417
TI  - Effect of long-acting somatostatin analogue (octreotide, SMS 201-995) plus
      calcium channel blocker (verapamil) on gallbladder contraction.
AB  - BACKGROUND/AIMS: In this study we investigated the effect of the long-acting
      somatostatin analog octreotide (SMS 201-995) plus calcium channel blocker
      (Verapamil) on gallbladder contraction. METHODOLOGY: Fourty healthy volunteers
      participated in this study. Gallbladder volumes were measured by ultrasonography.
      After recording the baseline measurement, the volunteers received either saline
      (n:10), or SMS 201-995 100 B microgram subcutaneously (s.c.) (n:10) or verapamil
      80 mg peroral (po) (n:10), or verapamil plus SMS 201-995 (n:10). Two hours later
      the gallbladder volumes were rescanned in 15 min intervals for 60 min. At the end
      all volunteers received standard liquid test meal (ensure 250 Cal/250 ml) and
      scans were again performed for one hour. RESULTS: The mean baseline gallbladder
      volume was 18.6 +/- 5.2 ml in all groups. The gallbladder volumes in the placebo
      group were 18.6 +/- 5.2 to 19.0 +/- 10.2 ml. In this group, after administration
      of test meal decreased the mean gallbladder volume to 14.3 +/- 7.5 to 8.4 +/- 5.8
      ml, but these values were not significantly different from the baseline values.
      In the verapamil group the volumes increased from 18.6 +/- 5.2 to 28.5 +/- 9.7 to
      30.8 +/- 11.6 ml. These values were significantly different from the baseline and
      the control group (p < 0.05). In this group, post-prandial mean volumes decreased
      to baseline in 30 min, but these values were higher than in the placebo group (p
      < 0.01). Verapamil-induced fasting the gallbladder relaxation was totally
      abolished to the placebo value by SMS 201-995. In verapamil plus SMS 201-995 and
      SMS 201-995 alone groups, the fasting and post-prandial volumes did not change
      when compared to the baseline value, but post-prandial volumes were higher than
      the placebo (p < 0.01). CONCLUSION: These results suggest that verapamil-induced
      gallbladder relaxation was totally abolished by SMS 201-995.

PMID- 9638418
TI  - A traumatic neuroma associated with obstructive jaundice after laparoscopic
      cholecystectomy.
AB  - A traumatic neuroma of the biliary tract is rarely associated with biliary
      obstruction. The authors describe a case of obstructive jaundice that occurred
      after laparoscopic cholecystectomy. Obstructive jaundice developed in a 39-year
      old woman 8 months after laparoscopic cholecystectomy. The stricture was resected
      and a Rouxen-Y hepaticojejunostomy was performed. Histological examination
      revealed a traumatic neuroma and a fibrous scar around the biliary duct. To our
      knowledge, a traumatic neuroma of the biliary tract after laparoscopic
      cholecystectomy has not been reported previously. Thermal injury may cause the
      late onset of a fibrous scar and traumatic neuroma. Therefore, traumatic neuroma
      should be included in the differential diagnosis when late-onset biliary tract
      obstruction develops after laparoscopic cholecystectomy.

PMID- 9638419
TI  - A case of early cancer in cystic intrahepatic duct associated with congenital
      choledochal cyst.
AB  - Herein, we report an extremely rare case of early cancer localized in the cystic
      intrahepatic duct, which is associated with the choledochal cyst including both
      the intra- and extrahepatic duct (type IV-A cyst). A small polypoid lesion in the
      cyst was detected by computed tomography. Extensive resection of the choledochal
      cyst with lobectomy was performed on the tumor in a 23-year-old woman. Tubular
      adenocarcinoma localized in the wall of the cystic left hepatic duct was
      histologically confirmed. Awareness of the diagnostic and treatment modalities,
      with a focus on potential malignancy in the cystic intrahepatic duct, in cases
      with anomalous arrangement of the pancreatobiliary duct is necessary.

PMID- 9638420
TI  - Correlation of macroscopic and histological characteristics in the regional lymph
      nodes of patients with rectal and sigmoidal adenocarcinoma.
AB  - BACKGROUND/AIMS: The number of involved lymph nodes is a relevant prognostic
      parameter which determines the duration of survival in patients with colonic and
      rectal adenocarcinoma. The purpose of this study was to establish a correlation
      between the macroscopic (size and consistency) and microscopic characteristics of
      the regional lymph nodes (type of involvement in tumor tissue, state of the
      capsule, adherence of the lymph nodes, etc.) in patients with colorectal
      carcinoma. METHODOLOGY: In this prospective study, 46 patients with rectal and
      sigmoid adenocarcinoma were studied through randomized selection. From the
      resected specimens, a total of 736 lymph nodes were identified (average 15.66 per
      patient), with the precise location determined according to Enker and
      Philiphsken. The macroscopic and microscopic characteristics of each lymph node
      were identified. These lymph node findings were then distributed by means of the
      x2 test, while the interrelationship of lymph node characteristics was determined
      by factor analysis. RESULTS: Within the group of "small" lymph nodes, 17.18% were
      malignant. Additionally, of all the malignant lymph nodes, 46.23% were less than
      5 mm in diameter. Although the malignant lymph nodes were predominantly diffusely
      involved within the tumor tissue, 19.50% were focally involved within the tumor
      tissue, of which 48.38% were "small" lymph nodes, which are commonly non
      palpable. Perforation of the capsule and adherence were more characteristic for
      focally mutated than for diffusely mutated lymph nodes in the cases of
      malignantly mutated lymph nodes. CONCLUSION: Size and consistency of the lymph
      nodes are not dependable parameters for appraisal of lymph node involvement in
      tumor tissue, the state of the lymph node capsule, nor the interrelation among
      the lymph nodes. As in the case of the primary tumor, local tumor aggression in
      the lymph nodes is conditioned by the grade of differentiation, i.e. histologic
      immaturity, rather than by tumor size.

PMID- 9638421
TI  - Discriminant analysis of pre- and intraoperatively detected prognostic factors
      influencing lymph node involvement in patients with colorectal carcinoma.
AB  - BACKGROUND/AIMS: The aim of this study was to establish whether, and to what
      extent, pre- and intraoperatively detected characteristics (demographic,
      anamnestic and laboratory data) and tumor characteristics can be used in the
      assessment of regional lymph node involvement in patients with colorectal
      carcinoma. The assessment also included the number of lymph nodes involved in
      patients with positive lymph nodes. Considering that the number of obtained lymph
      nodes widely varies in resected specimens, assessment parameters also included
      the percentage of the involved lymph nodes within the total population of lymph
      nodes. METHODOLOGY: From 1992-1993, 46 patients with carcinoma of the rectum and
      sigmoid colon were studied, with a total number of 736 lymph nodes evaluated. Out
      of the total number of lymph nodes, 577 (78.4%) were benign and 159 (21.6%),
      malignant. Data were analyzed by multi-variant statistical methods, namely:
      discriminant analysis and multiple regression with the aid of SPSS/PC+ software.
      RESULTS: For this patient group, we evaluated the following potentially
      predictive factors for lymph node involvement: age; serum hemoglobin, albumin and
      alkaline phosphatase levels; weight loss; and the primary tumor localization
      characteristics: histologic type, macroscopic growth pattern and depth of tumor
      invasion of the bowel wall. We found that there was no difference in the
      prediction of regional lymph node involvement between analysis of the
      aforementioned parameters and analysis of the isolated discriminators only.
      CONCLUSION: A predictability likelihood of 83.78% greatly surpasses the
      acceptable error tolerance level of 5%. Correlation of demographic, anamnestic
      and laboratory data about the patient and the characteristics of the primary
      tumor cannot be used in distinguishing malignant lymph nodes from benign ones.
      These data cannot be the basis for exact intraoperative staging and thus cannot
      be significant criteria for decision-making about operative treatment modalities.

PMID- 9638422
TI  - Measurement of rectal blood flow by laser Doppler flowmetry in inflammatory bowel
      disease.
AB  - BACKGROUND/AIMS: Vascular alterations have been suggested as pathogenic factors
      in inflammatory bowel disease, particularly Crohn's disease. The aim of our study
      was to assess rectal blood flow in patients with active inflammatory bowel
      disease involving the rectum. METHODOLOGY: Endoscopic measurement of rectal blood
      flow was performed by laser Doppler flowmetry in 45 subjects divided into three
      groups: healthy controls, ulcerative colitis and rectal Crohn's disease. RESULTS:
      Rectal perfusion was found to be significantly impaired in patients with
      ulcerative colitis, but not in those with Crohn's colitis. CONCLUSIONS: Our
      results confirm the role of local ischemia in ulcerative colitis, but do not
      support the theory that vascular factors play a key role in the pathogenesis of
      Crohn's disease.

PMID- 9638423
TI  - Diagnostic and treatment of Zenker's diverticulum: review of our series pharyngo
      esophageal diverticula.
AB  - BACKGROUND/AIMS: Clinical aspects and preneoplastic potential of Zenker's
      diverticulum justify its surgery. The clinical signs of the patients and the size
      of the diverticulum determine the surgical technique. METHODOLOGY: Between
      January 1974 and December 1995, 32 patients underwent surgery in our department.
      In order to compare the surgical technique, we divided the patients into 3
      groups: group A (cricopharyngeus myotomy: 15 patients (46.9%)), group B (myotomy
      with diverticulectomy: 15 patients (46.9%)) and group C (myotomy with
      diverticulopexy: 2 patients (6.7%)). The chi-square test was used for statistical
      analysis, p < 0.05. RESULTS: Local or regional anaesthesia was used in 7 patients
      from group A (46.6%); 5 patients from group B (33.3%) and all the patients from
      group C (100%). General anaesthesia was used in 8 patients from group A (53.4%),
      10 patients from group B (66.7%) and 0 patients from group C (0%). The overall
      mortality was 0%. The mean postoperative stay in group A was 6 +/- 2 days (3-10
      days); in group B was 11.6 +/- 6.4 days (5-25 days) and in group C was 3.5 +/-
      0.7 days (3-4 days). The mean postoperative stay in patients with local or
      regional anaesthesia was 5.3 +/- 1.6 days (3-9 days) and in patients with general
      anaesthesia, 10.9 +/- 6.1 days (4-25 days). No statistically significant
      difference was found between the anaesthetic technique and the surgical technique
      (p = 0.193), between the surgical technique and the mean postoperative stay (p =
      0.596) and between the anaesthetic technique and the mean postoperative stay (p =
      0.166). CONCLUSIONS: Cricopharyngeus myotomy is the main surgical technique,
      however, in diverticula longer than 3 cm of diameter it is mandatory to associate
      diverticulectomy. Diverticulopexy is indicated in patients of advanced age with a
      high surgical risk. Local or regional anaesthesia facilitates the identification
      of the diverticulum intraoperatively and reduce the mean postoperative stay,
      however, there is no statistical significant difference.

PMID- 9638424
TI  - Carcinoid somatostatinoma of the papilla of Vater: a case report.
AB  - A 57 year-old Japanese man with a carcinoid somatostatinoma of the papilla of
      Vater is presented. He was found to have cholecystolithiasis without any
      symptoms. Physical examination showed no abnormal findings. Routine laboratory
      data gave normal results, except for glucose intolerance and an elevated
      somatostatin concentration. A yellowish papillary tumor was found at the papilla
      of Vater, and histological examination suggested the diagnosis of carcinoid. He
      underwent a pancreatoduodenectomy in March 1992. The gallbladder contained a
      single pure cholesterol stone. Histological, immunohistochemical, and electron
      microscopic studies resulted in the diagnosis of a carcinoid somatostatinoma of
      the papilla of Vater, without regional lymph node metastases. Post-operative
      pancreatic juice output from the total pancreatic duct drainage increased to more
      than 1000 mL/day. Although an anastomotic leakage of the pancreatojejunostomy was
      noted, the pancreatic fistula closed 8 weeks later. His postoperative
      somatostatin value was normal. He has been well for 54 months following surgery,
      without any signs of recurrence.

PMID- 9638425
TI  - Intussusception of the small bowel due to Peutz-Jeghers syndrome: a case report.
AB  - We report the case of a 45-year-old woman with an intussusception of the small
      bowel due to Peutz-Jeghers syndrome. Immediate laparotomy was performed, and
      approximately 5 cm of the small bowel had to be removed because of ischemic
      areas. Six other polyps were removed through buttonhole enterotomies. The Peutz
      Jeghers syndrome is rare. Treatment is either surgery or a combination of surgery
      and intraoperative enteroscopy. Bowel resections must be kept to a minimum.

PMID- 9638426
TI  - Mesenteric neurofibroma with von Recklinghausen's disease: a case report.
AB  - Mesenteric neurofibroma associated with von Recklinghausen's disease is rare.
      Herein, we present one such case. A 15-year-old mentally retarded Japanese boy
      presented with destruction of the right 2nd and 3rd ribs on a routine chest
      roentgenogram. Physical examination revealed a funnel chest and multiple cafe-au
      lait spots, but no cutaneous nodules. Although the patient had no symptoms, a
      computed tomography (CT) and angiogram were performed. There were no definitive
      findings of malignancy in the tumors. However, since there were two risk factors
      for malignancy, specifically, a young age at the time of diagnosis and multiple
      tumors, and coupled with the size of the abdominal tumor which was large, the
      abdominal mesenteric tumor was removed. Pathological examination showed a
      neurofibroma with no evidence of malignancy.

PMID- 9638427
TI  - Infantile hemangioendothelioma with a highly elevated serum alpha-fetoprotein
      level.
AB  - Infantile hemangioendothelioma is the most common vascular tumor in infancy. A
      three-month-old infant was admitted to the hospital for hepatomegaly. Abdominal
      ultrasonography, a CT-scan, and MRI studies demonstrated bilateral diffuse
      hepatic nodules, which were characteristic of hepatic hemangioendothelioma. A
      highly elevated alpha-fetoprotein (AFP) level misled us to an impression of
      hepatoblastoma, but the pathology report through an open biopsy disclosed a liver
      hemangioendothelioma. The patient responded to methylprednisolone therapy. A
      follow-up sonogram revealed regression of the hepatic masses. This case
      emphasizes that an elevated AFP level of up to 400 ng/ml is normally found in
      some neonates until two months of age. Careful interpretation of this value is
      very important, especially when it is associated with a hepatic tumor. Herein, we
      present a case of infantile hemangioendothelioma in a three-month-old boy with a
      highly elevated serum AFP.

PMID- 9638428
TI  - Carcinoembryonic antigen and intra-arterial chemotherapy response of liver
      metastases.
AB  - BACKGROUND/AIMS: We investigated the relationship between serum carcinoembryonic
      antigen and response to hepatic artery chemotherapy for unresectable colorectal
      liver metastases. METHODOLOGY: The study included 14 patients with unresectable
      colorectal liver metastases receiving hepatic arterial chemotherapy weekly.
      Patients were evaluated monthly including liver function tests and
      carcinoembryonic antigen. Ten patients received high dose 5-fluorouracil (1000
      mg/m2) and 4 patients received other regimens. One patient underwent hepatectomy
      for cure after 5-fluorouracil. RESULTS: Thirteen patients (93%) had normal
      quality of life without toxicity during hepatic artery infusion. Response rate in
      the high dose 5-fluorouracil group was 50%, while the response rate of other
      regimens was 25%. Mean survival time differed between responding (n = 6) and non
      responding patients (n = 8) (527 vs 289 days), and the high dose 5-fluorouracil
      (n = 10) and other regimens (n = 4) (462 vs 213 days). In responding patients,
      peak serum carcinoembryonic antigen levels before hepatic artery infusion
      decreased within 6 months. In the non-responding patients, serum carcinoembryonic
      antigen levels increased rapidly despite hepatic artery infusion. CONCLUSIONS:
      Serum carcinoembryonic antigen levels correlated well with response. Hepatic
      artery infusional chemotherapy with high dose 5-fluorouracil may be recommended
      as effective treatment for unresectable liver metastasis from colorectal cancer
      if serum carcinoembryonic antigen levels decrease within 6 months.

PMID- 9638429
TI  - Glucagon and insulin metabolism in cirrhotic patients.
AB  - BACKGROUND/AIMS: The aim of this study was to investigate glucagon and insulin
      metabolism in order to clarify the mechanisms that lead to hyperglucagonemia and
      hyperinsulinemia in cirrhosis. METHODOLOGY: Splanchnic output and metabolic
      clearance rates were studied in 16 cirrhotic patients and 5 non-cirrhotic
      controls. Splanchnic glucagon and insulin output into the portal circulation were
      calculated by the difference between portal venous and systemic arterial
      concentration multiplied by portal plasma flow. The metabolic clearance rate was
      calculated as the ratio of output to systemic arterial concentration. Portal
      blood flow was measured by continuous local thermodilution. RESULTS: Arterial
      glucagon levels were higher in cirrhotics than in controls. Glucagon output was
      triple of that found in controls (52.4 +/- 7.0 vs 17.7 +/- 2.9 ng/min, p < 0.05).
      Both groups exhibited similar metabolic clearance rates of glucagon. Systemic
      arterial insulin values were higher in cirrhotics than in non-cirrhotics. Insulin
      output was not significantly different between the two groups. However, metabolic
      clearance of insulin in cirrhotics was reduced to one half of the rate found in
      controls (237.0 +/- 39.8 vs. 450.5 +/- 17.5 mL/min, p < 0.05). CONCLUSIONS:
      Hyperglucagonemia in cirrhotic patients results from increased pancreatic output,
      while hyperinsulinemia results from decreased insulin clearance.

PMID- 9638430
TI  - Determination of hepatic zinc content in chronic liver disease due to hepatitis B
      virus.
AB  - BACKGROUND/AIMS: Zinc is an essential, mostly intracellular, trace element which
      participates in many physiologic mechanisms. Some liver functions like urea
      formation require the presence of zinc; thus the determination of hepatic zinc
      content may contribute to the understanding of probable zinc-related clinical
      consequences of chronic liver disease. In this study, we aimed to determine the
      hepatic zinc concentrations in patients with chronic liver disease due to the
      Hepatitis B virus and to ascertain the relationship between the severity of liver
      disease and hepatic zinc content, if one in fact exists. METHODOLOGY: A total of
      99 HBsAg positive subjects were included in the study. We performed a liver
      biopsy on all subjects. Hepatic zinc concentrations were determined by atomic
      absorption spectrophotometry. RESULTS: The liver biopsies were normal in 25
      subjects. There were 33 chronic active hepatitis (CAH), 34 cirrhosis and 7
      chronic persistent hepatitis (CPH) patients in the study group. In the control
      group, CAH, cirrhosis and CPH groups, the mean liver zinc concentrations were
      3.83 +/- 1.86, 1.86 +/- 0.92, 1.14 +/- 0.68 and 3.74 +/- 1.81 mumol/g dry weight,
      respectively. Hepatic zinc in the CAH and cirrhosis groups were lower than that
      of the control group (p < 0.05). We also found that liver zinc in the cirrhosis
      group was lower than in the CAH group (p < 0.05). CONCLUSION: According to these
      results, as the severity of liver damage increases, the hepatic zinc
      concentration decreases. Therefore, it can be suggested that zinc supplementation
      may improve hepatic encephalopathy by increasing the efficiency of the urea
      cycle.

PMID- 9638431
TI  - Does hypothermic perfusion have beneficial effects for ischemic liver during
      extended hepatectomy with hepatic inflow occlusion of canine liver? A comparative
      study with topical cooling.
AB  - BACKGROUND/AIMS: The present study was designed to elucidate the effect of
      topical cooling and hypothermic perfusion in extended hepatectomy under hepatic
      inflow occlusion. Hypothermic perfusion has provided to have a protective effect
      on the ischemic liver. However, it has not been determined whether hypothermia or
      perfusion had salutary effects on the ischemic liver. METHODOLOGY: Seventy-five
      percent of the liver was resected under hepatic inflow occlusion for 60 minutes
      in each adult mongrel dog. The animals were divided into three groups; no cooling
      group (n = 8), topical cooling group (n = 7) using ice slush and hypothermic
      perfusion group (n = 7). Blood from the hepatic vein was sampled for measurement
      of ALT, AST, LDH and purine nucleoside phosphorylase. RESULTS: The seven-day
      survival in topical cooling group and hypothermic perfusion group was better
      compared with that in no cooling group. ALT, AST and LDH levels showed no
      significant differences among the groups. PNP levels were significantly lower in
      topical cooling group (p < 0.01) and hypothermic perfusion group (p < 0.05) than
      in no cooling group, but no significant differences between topical cooling group
      and hypothermic perfusion group. CONCLUSIONS: In the hepatic ischemia for 60
      minutes, hypothermic perfusion did not demonstrate markedly better effects
      compared with topical cooling.

PMID- 9638432
TI  - Significance of the peroral phenolsulfonphthalein test in hepatic resection: a
      possible predictor of bacterial translocation.
AB  - BACKGROUND/AIMS: The aim of this study was to evaluate the perioperative changes
      in intestinal permeability by using the phenolsulfonphthalein (PSP) test and to
      also to clarify the significance of the peroral PSP test in hepatic resection.
      METHODOLOGY: Fifty patients, all of whom underwent hepatic resection, were
      prospectively studied. Postoperative complications occurred in 16 patients, and
      10 of these complications were infectious. A peroral PSP test, which was
      scheduled before operation and on postoperative days 3, 7, and 14, was performed
      as follows: after the administration of 30 mg of PSP, a 24-hour urine was
      collected, and the urinary PSP was measured by colorimetric assay. The
      correlation between the preoperative PSP value and various clinical variables,
      such as perioperative changes in urinary PSP excretion, and the relationship
      between the postoperative PSP value and postoperative complications, were
      investigated. RESULTS: Preoperative urinary PSP excretion was found to increase
      in proportion to the degree of liver dysfunction. In contrast, urinary PSP
      excretion did not significantly change during the perioperative period. However,
      urinary PSP excretion on postoperative day 3 in patients with postoperative
      infectious complications (27.3%) was significantly greater than that in those
      without infectious complications (17.4%; p < 0.05). Furthermore, PSP excretion on
      postoperative day 3 in those with infectious complications was also significantly
      greater as compared to the preoperative level. The patients with a urinary PSP
      excretion level on postoperative day 3 of greater than 25%, exhibited infectious
      complications more frequently than patients with a level under 25% (60% versus
      10.3%, respectively; p < 0.05). CONCLUSIONS: The peroral PSP test is thus
      suggested to be a possible predictor of bacterial translocation after hepatic
      resection.

PMID- 9638433
TI  - Treatment of chronic hepatitis C genotype 4 with alpha-interferon in Saudi
      Arabia: a multicenter study.
AB  - BACKGROUND/AIM: Several studies have indicated that there are certain predictive
      factors (gender, duration of infection with HCV, cirrhosis and genotype of HCV)
      of a better response with alpha-interferon treatment in patients with chronic
      hepatitis C. The aim of this study was to evaluate these factors in Saudis and
      other Arab nationals with chronic hepatitis C-genotype 4-undergoing alpha
      interferon treatment. METHODOLOGY: A multicenter study was conducted between 1992
      and 1994 on 80 consecutive patients who were prospectively recruited and
      randomized in treatment and control groups. RESULTS: The results of this
      multicenter study indicated a low response rate to alpha-interferon with an
      overall response rate of 43%, of which 28% was complete. The sustained response
      was only 16%. Among the reasons for this low response in our study are the high
      percentage of patients with cirrhosis and the long infection interval, as about
      80% of our HCV cases were community-acquired. CONCLUSION: Liver cirrhosis was
      found to be the main predetermining factor for response to interferon treatment.
      Genotype 4 was not a contributing factor to the difference in response rate.

PMID- 9638434
TI  - Synchronous hepatocellular carcinoma or metastatic hepatic tumor with primary
      gastric cancer.
AB  - BACKGROUND/AIMS: When a solitary hepatic tumor occurs synchronously with gastric
      cancer, it is usually presumed to be metastatic. However, this may not be true in
      a place like Taiwan, where hepatocellular carcinoma (HCC) is prevalent. This
      study was conducted to examine the clinicopathological factors of both
      conditions. METHODOLOGY: A retrospective analysis of 14 patients who underwent a
      synchronous hepatectomy in combination with radical gastrectomy over the past 15
      years was performed. RESULTS: Seven patients had metastatic gastric cancer, and
      seven had concomitant gastric and hepatic cancer. Serosal invasion and lymph node
      metastasis were the major features in the patients with metastatic gastric
      cancer. Early gastric cancer was found in three of the patients with the
      coexisting primary cancers. No patient with solitary metastatic cancer survived
      more than one year, but long-term survival of more than two years was achieved in
      two patients with the two forms of cancer. CONCLUSIONS: Double cancer of the
      stomach and liver should be kept in mind in patients with gastric cancer
      concomitant with a solitary hepatic tumor, in order to provide optimal treatment.

PMID- 9638435
TI  - Treatment of benign hepatic cysts by instillation of tetracycline hydrochloride.
AB  - BACKGROUND/AIMS: Despite the high frequency of benign hepatic cysts, they rarely
      cause symptoms. Large cysts, however, may produce clinical manifestations. In
      these cases, ultrasonography-guided therapy has been proposed. We report the
      results of this therapy in patients with symptomatic benign hepatic cysts.
      METHODOLOGY: Seven patients with non-parasitic, non-neoplastic benign hepatic
      cysts were submitted to fine-needle ultrasonography-guided aspiration, followed
      by injection of diluted tetracycline hydrochloride (1 g). In all cases, cytology,
      tumour markers and microbiology analysis of aspirates were performed. One patient
      required two sessions. The grade of patient satisfaction and ultrasonography
      changes were assessed 1, 3 and 6 months after the procedure. RESULTS: Cyst size
      decreased in all patient, with total collapse in three. No major complications
      occurred. Cytology, alpha fetoprotein, CA19.9, CEA and microbiology of the cyst
      fluid confirmed the initial ultrasonographic diagnosis of simple biliary cysts.
      Clinical complaints improved in 2 cases, and 5 patients became asymptomatic.
      Ultrasonography evaluation 3 months after the procedure was more reliable in
      predicting successful treatment. CONCLUSION: Intracystic instillation of
      tetracycline hydrochloride is an effective and safe technique and may become the
      first choice therapy for benign hepatic cysts.

PMID- 9638436
TI  - Point mutations in the S and pre-S2 genes observed in two hepatitis B virus
      carriers positive for antibody to hepatitis B surface antigen.
AB  - Two hepatitis B virus (HBV) carriers who had antibodies to HBV surface antigen
      (anti-HBs) were studied. Case 1 was a 47 year old woman positive for hepatitis B
      e antigen (HBeAg), and case 2 was a 61 year old man positive for antibody to
      HBeAg (anti-HBe) and DNA-polymerase (DNA-p). Neither case had received the HBV
      vaccine. The nucleotide sequences of the HBV-DNA extracted from the patients'
      sera were determined within the pre-S2 and S genes. Seven out of nine S gene
      clones from case 1 and six out of nine S gene clones from case 2 had an amino
      acid replacement from Thr or Ile to Ser at codon 126 in the alpha-determinant of
      the S gene. Amino acid substitution of codon 145 of the S gene previously
      reported was not observed. Although two previous reports on HBV escape mutant
      carriers with both anti-HBs and HBeAg described some deletions in the pre-S2
      gene, our cases did not show these deletions. Our analysis indicated that
      carriers with the HBV escape mutant did not always have pre-S2 gene deletions. We
      found two HBV escape mutant carriers who had amino acid substitutions at codon
      126 in the S gene due to point mutation without any deletions in the pre-S2 gene.

PMID- 9638437
TI  - Jejunal variceal bleeding after esophageal transection in a patient with
      idiopathic portal hypertension.
AB  - This report describes a 38-year-old man with massive gastrointestinal bleeding
      from jejunal varices. He had been previously diagnosed to have idiopathic portal
      hypertension and esophageal varices, and had undergone an esophageal transection
      8 years earlier. The pre-operative diagnosis was a suspected hemorrhage from the
      small intestine as visualized by 99mTc-HSAD scintigraphy (technetium 99m-labeled
      human serum albumin D-type) and was not considered to be repeated massive lower
      GI tract bleeding. An exploratory laparotomy was performed, and intra-operative
      endoscopy revealed active bleeding from the jejunal varices. A partial resection
      of the small intestine resulted in a complete resolution of the bleeding. A
      review of the literature thereafter disclosed twelve previously reported cases of
      jejunal variceal bleeding.

PMID- 9638438
TI  - Left hepatic vein kinking after right trisegmentectomy: a potential cause of
      postoperative liver failure.
AB  - We report a case of left hepatic vein kinking which caused severe congestion of
      the left lateral segment after right trisegmentectomy for a large liver tumor.
      Intraoperative doppler ultrasonography documented an 80% reduction of the left
      hepatic vein blood flow when the left lateral segment was rotated into the right
      subphrenic space.

PMID- 9638439
TI  - Graft mass and volume calculation in living related donors for liver
      transplantation.
AB  - Living related liver transplantation is one of the strategies currently used to
      increase the donor pool. A preoperative and non-invasive estimate of the donor's
      liver volume is needed to ensure sufficient functional liver reserve for survival
      after resection, and to obtain a graft of adequate volume to suit the recipient's
      features. A method based on a preoperative abdominal computerised axial
      tomography of the donor, that enables the volume and mass of the whole liver, and
      the graft, to be calculated is herein described. The compatibility of the
      estimate with real graft mass after its removal has been proved, and the accuracy
      of the calculi has been compared with other published methods. Moreover,
      progressive growth of the recipient liver remnant has been demonstrated in
      subsequent explorations.

PMID- 9638440
TI  - Fibrolamellar hepatocellular carcinoma--an atypical MR manifestation.
AB  - We report the imaging findings, specifically magnetic resonance pictures of a non
      cirrhotic case of fibrolamellar hepatocellular carcinoma in an older patient (60
      years). Computed tomography revealed non-enhanced hypodense central scar without
      notable intratumoral calcification. MR imaging revealed a mass, which was
      homogeneously hypointense on T1-weighted images (T1WI) and turned hyperintense on
      T2-weighted images (T2WI). Stellate central scar was depicted with more
      hypointensity on T1WI, however, it became markedly hyperintense on T2WI. This
      manifestation is very different from the typical pattern reported in the
      literature. In gadolinium enhanced T1WI, the mass other than the central scar got
      enhanced. Fibronodular hyperplasia and fibrolamellar hepatocellular carcinoma
      should be differentiated with reference to the clinical and imaging findings.
      Collagenous central scar was described pathologically within the latter. However,
      a discrepancy between the pathological and magnetic resonance pattern concerning
      the central scar which was collagenous and corresponding to hyperintensity on
      T2WI was found. To our knowledge no similar entity has been described in the
      literatures so far.

PMID- 9638441
TI  - Isoflurane hepatotoxicity in a patient with a previous history of halothane
      induced hepatitis.
AB  - Halogenated volatile anesthetics have been associated with liver injury. Most
      reported cases have been linked to halothane and enflurane. Cross-sensitization
      between the latter agents has also been documented. Isoflurane hepatitis is
      extremely rare, and only a few convincing cases have been published. Moreover,
      clinical cases of cross-sensitization of isoflurance with other haloalkanes have
      not been reported. We describe a case of hepatic dysfunction 2 weeks after
      isoflurance anesthesia in a 35-year-old obese woman with a previous history of
      halothane hepatitis. The diagnosis was made on the basis of exposure to
      isoflurance, the delay between the time of exposure and the onset of jaundice,
      and the exclusion of other causes of liver dysfunction. This case reiterates the
      recommendation that patients who sustain liver injury from one haloalkane should
      not be exposed to another.

PMID- 9638442
TI  - Separate histogenesis of combined hepatocellular and cholangiocellular carcinoma
      in two patients.
AB  - Double primary liver carcinomas, i.e. hepatocellular carcinoma (HCC) and
      cholangiocellular carcinoma (CCC) are rare. Two patients in whom double primary
      liver carcinomas were surgically resected are described herein. Case 1: A 51-year
      old Japanese man with chronic type B hepatitis underwent hepatectomy for primary
      HCC with intrahepatic metastasis. Case 2: A 67-year-old Japanese man with a
      history of rectal cancer and CCC underwent lateral hepatic segmentectomy for a
      suspected recurrence of intrahepatic CCC. Lack of direct contact between tumors,
      no evidence of histological transition and clearly different immunohistochemical
      staining for cytokeratin support a distinct histogenesis of the tumors in these
      two patients. The findings indicate that combined HCC and CCC can arise
      synchronously or metachronously as an intrahepatic double cancer.

PMID- 9638444
TI  - Pancreatic head resection with segmental duodenectomy and preservation of the
      gastroduodenal artery.
AB  - BACKGROUND/AIMS: Duodenum-preserving pancreatic head resection has been performed
      for benign pancreatic head diseases. Complete resection of the pancreatic head
      with preservation of common bile duct and the duodenum sometimes causes common
      bile duct or duodenal necrosis due to ischemia. We propose the simple, easy and
      safe procedure for complete resection of pancreatic head with segmental
      duodenectomy to prevent complications, which may be caused on duodenum preserving
      pancreatic head resection. METHODOLOGY: Pancreatic head resection with segmental
      duodenectomy including minor and major papilla was performed. By conserving the
      right gastric artery, 5 to 7 cm of the first portion of the duodenum is preserved
      with good arterial circulation. In addition, by conserving the anterior inferior
      pancreaticoduodenal artery, the third portion and anal side of the second portion
      of the duodenum are preserved with good arterial circulation. Resection of the
      pancreatic head with 3 to 4 cm of segmental duodenectomy including minor and
      major papilla completes this procedure. Reconstruction of the alimentary tract is
      then performed with pancreatogastrostomy, end to end duodenoduodenostomy and end
      to side choledochoduodenostomy. RESULTS: In 14 cases of pancreatic head diseases,
      chiefly benign tumors, this procedure was successfully performed without severe
      complications. Postoperative quality of life was quite satisfactory. CONCLUSION:
      Using this procedure, complete resection of the pancreatic head for benign tumor
      of the pancreatic head region can be performed safely and effectively.

PMID- 9638443
TI  - Epithelial anomalies in chronic pancreatitis as a risk factor of pancreatic
      cancer.
AB  - BACKGROUND/AIMS: The relationship between chronic pancreatitis and the
      development of pancreatic cancer is still a matter of dispute. Our aim was to
      determine the frequency of hyperplastic, metaplastic and dysplastic epithelial
      anomalies in the course of chronic pancreatitis and the potential steps in their
      development to malignancy. METHODOLOGY: The study was based on biopsy material of
      70 patients with clinically diagnosed advanced chronic pancreatitis, who
      underwent partial or total pancreatectomy, as well as other operations. The
      patients were assigned to 2 groups: Group I (n = 41) with calcifying chronic
      pancreatitis; Group II (n = 29) with other forms of the disease. Histological
      sections were stained with hematoxylin-eosin, Mallory-azan, Gomori's silver
      method, and glycosaminoglycans (PAS and Alcian blue staining). Special interest
      was focused on the type and incidence of epithelial ductal and acinar cell
      anomalies, and on the degree of parenchymal scarring. RESULTS: Hyperplasia of the
      ductal epithelium was present in 31.4%, focal squamous metaplasia in 21.4%,
      mucous metaplasia in 11.1%, cellular dysplasia in 8.6%, dysplastic acinar cell
      nodules in 21.4%, and "tubular complexes" in 30.0% of all cases. The differences
      in the frequency of these changes, except for ductal epithelial hyperplasia, were
      not statistically significant in two comparable groups. Advanced pancreatic
      fibrosis was associated with epithelial anomalies in 65.7% of all cases.
      CONCLUSIONS: From the morphological point of view, the adequate prerequisites for
      the consideration of advanced forms of chronic pancreatitis, independent of type,
      as a risk factor of pancreatic cancer exist, necessitating the surgical removal
      of pathological lesions.

PMID- 9638445
TI  - Factors predictive of the healing of pancreatic pseudocysts treated by
      percutaneous evacuation.
AB  - BACKGROUND/AIMS: Pseudocyst formation is a well-known complication of
      pancreatitis which develops over 1 to 4 weeks in approximately 15% of patients.
      Nearly one-third of pancreatic pseudocysts resolve spontaneously; however, if
      there is no resolution within six weeks, evacuation must be performed. The aim of
      this study was to prospectively assess the reliability of the following:
      etiology; location; amount of pseudocyst liquid; and concentrations of certain
      biochemical parameters (LDH, glucose, proteins, sodium, potassium, bilirubin,
      lipase and amylase) in the pseudocyst content and patients' serum, in terms of
      the efficacy of ultrasound-guided percutaneous evacuation as a therapeutic
      approach. METHODOLOGY: Pseudocyst fluid was obtained by ultrasound-guided
      percutaneous evacuation in 67 patients, with a history of pancreatitis and
      pancreatic pseudocysts larger than five centimeters in diameter, with a matured
      membraneous wall that persisted for more than six weeks. RESULTS: There is a
      prognostic value associated with the location of the pseudocyst, the amount of
      pseudocyst liquid and the concentration of proteins, potassium, lipase and
      amylase in the evacuated material. CONCLUSION: Analysis of the aforementioned
      parameters provides an early forecast of the outcome of percutaneous evacuation.

PMID- 9638446
TI  - Solid cystic tumor of the head of the pancreas in a young woman.
AB  - This a case report of a solid papillary tumor of the pancreas in a young woman of
      18 years, who was referred to after having suffered for a period of 8 months with
      a rather vague symptomatology, characterized by dyspepsia, fatigue and, towards
      the end of the 8 month period, weight loss (approximately 2 kg). In the last
      week, as a consequence of a modest abdominal trauma, the patient was submitted to
      abdominal CT that showed a burden at the head of the pancreas, demonstrating a
      round neoformation about 6 cm in diameter with solid echogenicity slightly
      hypodense. Subsequently, she underwent an operation with the diagnosis of
      pseudocystis of the pancreas. During surgery, a big cystic formation of the head
      of the pancreas, into which a drain was introduced, was revealed. The
      histological postoperative examination was compatible with pancreatic tumor with
      a low grade of malignancy, cystic papillary or solid papillary type. Therefore,
      the patient came under our observation and underwent an operation of
      pancreatoduodenectomy. Two years after the operation, the patient had completely
      recovered. In this case, we discussed the problem of performing certain
      preoperative diagnoses despite the aid of modern diagnostic imaging, this being a
      very rare illness that almost exclusively plagues young women (median age 19
      years). This diagnosis has an uncertain histological origin and is generally
      accompanied by a modest and vague symptomatology. The surgical procedure, given
      the low grade of malignancy of the neoplasm and the excellent long-term
      prognosis, must be, with respect to the oncological radicality, as conservative
      as possible.

PMID- 9638447
TI  - A new porto-systemic bypass technique for hepatopancreatoduodenectomy with portal
      vein resection.
AB  - When reconstructing the portal vein (PV) following hepatopancreatoduodenectomy
      (HPD) with PV resection, a new porto-systemic bypass (PSB) technique can be
      employed to prevent intestinal vascular congestion. The Whipple procedure is
      performed in a standard manner, as long a portion of the gastrocolic trunk is
      preserved for insertion of an antithrombogenic catheter (ATC). After harvesting
      the left external iliac vein and exposing the right great saphenous vein, the end
      of the ATC is inserted in the superior mesenteric vein via the gastrocolic trunk
      in the distal direction and the other end of the ATC is inserted in the greater
      saphenous vein. PSB is achieved as a result of the venous pressure gradient. By
      employing this technique, an ATC can be inserted without damaging another
      mesenteric venous branch and with minimal damage to the endothelium, and the
      small intestine is not exposed in the operative field until enteric
      reconstruction is started. This technique is a promising option for PSB during
      HPD with PV resection.

PMID- 9638448
TI  - Tyrosine hydroxilase activity in discrete brain regions from prehepatic portal
      hypertensive rats.
AB  - BACKGROUND/AIMS: Portal hypertension in patients and rat models are characterized
      by splanchnic and systemic hemodynamic alterations. Both the central and
      autonomic nervous systems are implicated in its pathophysiology. The aim of our
      research was to study the tyrosine hydroxylase activity and the rate limiting
      step in the biosynthesis of catecholamines in partial ligated portal hypertensive
      and in control rat brains. METHODOLOGY: The following seven discrete brain
      regions were investigated: Subfornical Organ, Organum Vasculosum Lamina
      Terminalis, Median Eminence, Periventricular Nucleus, Area Postrema, Locus
      Coeruleus and Nucleus Tractus Solitarius. RESULTS: The enzyme activity showed a
      significant increment in six nuclei and a decrease in Area Postrema Nucleus when
      portal hypertensive rats were compared to controls. CONCLUSIONS: These results
      suggest the participation of some discrete brain regions in the mechanism of
      hepatic portal hypertension under the present rat model.

PMID- 9638449
TI  - Metallic stents for low invasive recanalization of the portal veins with
      cancerous invasion--first case report.
AB  - BACKGROUND/AIMS: Portal venous stenosis caused by cancer invasion has been
      difficult to treat and patients do not have any treatment options. On the other
      hand, protal venous stents have been applied to patients with variceal
      haemorrhaging associated with portal vein thrombosis. However, there have not
      been any reports concerning portal venous stents for malignant portal stenosis.
      The aim of this report was to apply metallic stent for malignant portal stenosis
      to reduce portal hypertension and restore portal venous blood flow, which in turn
      leads to the recovery of liver function. METHODOLOGY: Two patients with portal
      hypertension caused by malignant portal stenosis were treated by metallic stent
      implantation. In one case, the stent was applied intraoperatively via the ileal
      vein and in the other case, it was applied postoperatively via transhepatic
      portal cannulation. RESULTS: In the first case, portal pressure monitored before
      and after placement of the stent was 350 mmH2O and 200 mmH2O, respectively. Liver
      function tests showed normalization after stent placement. In the second case,
      over 3000 ml of ascites, which were drained through the drainage catheter every
      day, could be reduced remarkably, and one week later, the catheter could be
      withdrawn. Portal pressure before and after embedding the stent was 410 and 275
      mmH2O, respectively. Both patients were discharged from the hospital and their
      recovery was uneventfully. CONCLUSION: Both cases had an uneventful postoperative
      course, with normalization of liver function and cessation of ascites on the next
      postoperative day in case 2. Thus, portal venous stent should be considered a
      viable option for the treatment of malignant portal stenosis.

PMID- 9638450
TI  - Laparoscopic splenectomy with the newly devised morcellator.
AB  - BACKGROUND/AIMS: One of the major hurdles to overcome in the development of
      laparoscopic surgery has been finding effective extraction techniques for the
      removal of large tissue masses. The electromechanical morcellator makes it easy
      to remove relatively large sections of tissue from the abdomen through the
      existing incisions. To determine the safety and efficacy of the new morcellator
      in laparoscopic splenectomy, our preliminary experiences using the morcellator
      were reviewed and retrospectively compared with the results in patients who
      previously underwent conventional extraction techniques. METHODOLOGY: From
      February 1992 to March 1996, 31 patients underwent laparoscopic splenectomy. In
      the last eight patients, the new morcellator was used to remove the spleen, while
      in the remaining 23 patients, a laparoscopic splenectomy was performed using the
      conventional extraction techniques. RESULTS: In the last eight patients who
      underwent laparoscopic splenectomy, the newly devised morcellator was
      successfully used without any complications. The spleen could be removed from the
      abdominal cavity in an average of 15.9 +/- 10.4 minutes using the morcellator,
      while the average was 45.7 +/- 15.4 minutes using conventional techniques. It was
      not necessary to extend the skin incision in patients with the morcellator,
      while, on the other hand, a 2-cm extension of the existing skin incision was
      always required to remove the spleen in the latter method. CONCLUSION: The
      morcellator was found to be an effective device which can safely, efficiently and
      rapidly remove tissue masses. This procedure is therefore considered to be one
      feasible way to solve the age-old problem of intracorporeal morcellation.

PMID- 9638451
TI  - Jejunal pouch with nerve preservation and interposition after total gastrectomy.
AB  - BACKGROUND/AIMS: In this paper, we describe operative technique details and our
      results with a modified technique for jejunal pouch formation and interposition
      after total gastrectomy, with an overall aim to achieve results superior to
      jejunal pouch and Roux-en-Y reconstruction, as reported in the literature.
      METHODOLOGY: Following total gastrectomy, the jejunum was divided approximately
      20 cm distal to the ligament of Treitz. Marginal vessels were not divided in
      order to preserve the nerves in the 50 cm of distal jejunum which would be used
      for pouch construction. The pouch was constructed using a linear stapler (Endo
      GiA, United States Surgical Corp., Norwalk, Conn). A total of 15 gastric cancer
      patients underwent construction of a nerve-preserving jejunal pouch and
      interposition following total gastrectomy. RESULTS: None of the patients
      experienced postoperative complications due to pouch construction. Additionally,
      discomforts such as dumping or stagnation were not observed. Mild reflux
      esophagitis occurred in five of the 15 patients and was resolved by oral
      administration of camostat mesilate. Six months after surgery, the average
      patient's diet volume and body weight had gradually increased to 79% and 86%,
      respectively, of the presurgical levels. A dual phase, dual isotope radionucleid
      pouch emptying study was also performed six months after surgery. The intra-pouch
      RI retention rate was 47% for liquid food and 53% for solid food 120 minutes
      after intake. The emptying rate was slower for both solid and liquid food, as
      compared with healthy individuals. CONCLUSIONS: The pouch-emptying test
      demonstrated a satisfactory retention capacity and an acceptable emptying time as
      a gastric substitute. The patients who underwent gastric reconstruction with a
      nerve-preserving jejunal pouch with interposition have experienced a reasonably
      good quality of life.

PMID- 9638452
TI  - The incidentally found leiomyoma that was in a resected stomach and its follow
      up.
AB  - BACKGROUND/AIMS: A prospective study measured the occurrence of leiomyoma in
      patients receiving various gastric surgeries and the probable characteristics of
      patients presenting an incidental leiomyoma. METHODOLOGY: Twenty-eight (3.5%)
      patients with gastric leiomyoma were encountered among 796 resected stomach
      specimens within the past two years. Of these patients, 11 exhibiting a
      submucosal tumor were preoperatively diagnosed with endoscopy, whereas 17 showing
      leiomyoma were incidentally found during a thorough survey of the resected
      stomach specimens. Their demographic characteristics were compared. RESULTS:
      Occurrence of incidental leiomyoma tended to be more common in patients with
      gastric cancer than in other lesions (3.2% vs 0.9%, p = 0.0513). Comparing the
      characteristics of patients showing incidental leiomyoma and pre-operatively
      diagnosed submucosal tumor, their differences in age, gender, tumor location or
      number were not significant. However, the former usually exhibited tiny lesions
      without an overlying necrotic ulcer. Recent endoscopic follow-up did not find any
      evidence of recurrence. CONCLUSIONS: Incidental leiomyoma is not rare in resected
      specimens. Most lesions are tiny without overlying ulcer and gross recurrence
      looks impossible. Pre-operative diagnosis of this lesion remains difficult since
      a warning sign of leiomyoma never exists.

PMID- 9638453
TI  - Effect of histamine on thyrotropin-releasing hormone and somatostatin secretion
      in rat stomach.
AB  - BACKGROUND/AIMS: Histamine plays an important role in gastric function, and the
      histaminergic system is involved in the regulation of neuropeptides and gastric
      acid secretion. METHODOLOGY: We investigated the effect of histamine and
      histamine receptor antagonist (HRA) on the intraluminal secretion of thyrotropin
      releasing hormone (TRH) and somatostatin (SOM) using a rat luminal perfusion
      model. RESULTS: Intravenous administration of histamine caused an increase in TRH
      secretion and a decrease in SOM secretion preceding a decrease in pH in the
      perfusate. When the total contents of TRH and SOM in the perfusate were
      calculated after administration of histamine, the effect of histamine was found
      to be dose-dependent in both neuropeptide secretions. Under basal conditions,
      neither H1RA, H2RA, nor H3RA caused changes in TRH secretion into the perfusate.
      In contrast, H2RA and H3RA yielded an increase in basal SOM secretion. When
      administered before the injection of histamine, H2RA caused a complete inhibition
      of histamine-induced changes in TRH and SOM secretion. Preadministration of H3RA
      also induced a weak but significant inhibition of the changes in neuropeptide
      secretion. CONCLUSION: It was concluded that paracrine pathways do exist among
      histamine, TRH, and SOM in the regulation of gastric acid secretion.

PMID- 9638454
TI  - Gastroenterological surgery for patients with chronic respiratory insufficiency.
AB  - BACKGROUND/AIMS: The aim of this study was to clarify the surgical indications
      for patients with chronic respiratory insufficiency. METHODOLOGY: Fourteen
      patients with chronic respiratory insufficiency who underwent abdominal surgical
      procedures, were retrospectively studied. The surgical indications were carefully
      determined based primarily on the performance status (PS) of each patient and
      cardiopulmonary function tests. A PS of equal to or less than 3, which meant the
      patient's status required bed rest > 50% of the time, and the need for assistance
      in performing normal activities were all factors considered for surgical
      indications. RESULTS: During the period studied, two patients were excluded from
      the surgical indications due to the fact that one was at a terminal stage of
      pulmonary disease and was completely bedridden (PS = 4), while the other
      demonstrated active pneumonia with a considerable amount of purulent sputa.
      Regarding the pulmonary function tests for patients who underwent surgery, the
      lowest limits of those examinations were as follows: 810 ml of vital capacity
      (VC), 23.8% of predicted VC, 610 ml of forced expiratory volume in one second
      (FEV1.0), 38.6% of predicted FEV1.0, 50.5 mmHg of PaO2 while inhaling 4 liters of
      oxygen and 73.8 mmHg of PaCO2. No surgery related mortality or hospital death
      within 30 days after operation was observed. Only two patients had
      cardiopulmonary complications (consisting of pulmonary edema with atrial
      fibrillation in one patient, and acute myocardial infarction in another patient).
      However, neither pneumonia, prolonged ventilatory support for more than 2 days,
      nor the need for a tracheostomy after surgery was observed. CONCLUSIONS:
      Gastroenterological surgery is thus considered to be indicated even for patients
      with chronic respiratory insufficiency, as long as the PS can be maintained (PS
      of equal to or less than 3) and no active pneumonia with a considerable amount of
      purulent sputa is present.

PMID- 9638455
TI  - Histologic types and surveillance of gastric polyps: a seven year clinico
      pathological study.
AB  - BACKGROUND/AIMS: This is a seven-year prospective study based on all gastroscopic
      examinations of our patient population in order to study gastric polyps.
      METHODOLOGY: One hundred and twenty-one polyps, removed from 96 patients were
      analysed. All polyps, after endoscopic polypectomy, were classified according to
      their histotype. The follow-up was carried out in 49 patients for a mean time of
      40 months. RESULTS: Polypoid lesions were more frequent in females (57.3%) and
      they were preferentially located in antrum (60.3%). Hyperplastic and inflammatory
      polyps were 55.4% and 28.9%, respectively, while adenomatous lesions were 9.9%.
      Four fundic gland polyps, 1 carcinoid, 1 type I early gastric cancer and 1
      pancreatic heterotopia were also found. During the follow-up no malignant lesion
      was encountered. On the other hand 25 benign polyps were found in 19 patients.
      CONCLUSIONS: Our experience confirms that there is a close relationship between
      the size of the polyps and the neoplastic change. In fact, in our series all
      polyps were smaller than 2 cm and only one malignancy was found (an early gastric
      cancer). None of adenomatous polyps was associated with gastric adenocarcinoma.
      Our data also indicates that when a polypectomy is carried out for small polyps
      (smaller than 2 cm.) a strict follow-up is necessary for the neoplastic polyps
      only.

PMID- 9638456
TI  - Poor prognosis in early gastric cancer complicated by five or more positive
      nodes.
AB  - BACKGROUND/AIMS: Despite the increased frequency of early gastric cancer, little
      is known about the clinicopathological features of early gastric cancers
      complicated by lymph node metastasis. This study was designed to determine
      whether the number of involved lymph nodes is associated with prognosis in
      patients with early gastric cancer. METHODOLOGY: Fifty one patients with node
      positive early gastric cancer were reviewed retrospectively from hospital
      records. The patients were divided into two groups according to the number of
      positive nodes: a) 40 patients with 1-4 positive nodes, b) 11 patients with 5 or
      more positive nodes. RESULTS: The patients with 5 or more positive nodes showed
      poorer prognosis than patients with less than 5 positive nodes. CONCLUSIONS:
      Early gastric cancer patients with 5 or more positive nodes show a poorer
      prognosis than early gastric cancer patients with less than 5 positive nodes.
      Since surgery alone cannot completely cure patients with early gastric cancer
      complicated by 5 or more positive nodes, intensive postoperative chemo
      immunotherapy should be administered to these patients.

PMID- 9638457
TI  - The course of Helicobacter pylori infection after partial gastrectomy for peptic
      ulcer disease.
AB  - BACKGROUND/AIMS: While the number of patients operated on for peptic ulcer
      disease is decreasing, many underwent surgery before the Helicobacter pylori era.
      Some of them later develop ulcer relapses. The aim of this study was to evaluate
      the course of H. pylori infection in the gastric remnant after surgery for peptic
      ulcer disease. METHODOLOGY: This study included 90 consecutive partial
      gastrectomy patients, obtained from gastroscopy registers of the Department of
      Surgery, Helsinki University Central Hospital, between 1985 and 1988, in whom
      both pre- and postoperative samples were available. All of the patients had
      undergone partial gastrectomy at some time between 1925 and 1988. The median
      interval between operation and reference gastroscopy was 5 years. RESULTS: Twenty
      three patients had a recurrent ulcer, and an additional six patients had a
      history of an earlier ulcer recurrence. Preoperative H. Pylori infection (68%)
      did not correlate significantly with the ulcer recurrence rate. The recurrence
      rate was higher in patients with Billroth I (BI) (27%) and Billroth II (BII)
      (33%) reconstructions than in those with a Roux-en-Y type reconstruction (9%, BII
      vs Roux-en-Y, p = 0.02, BI vs Roux-en-Y, p = 0.12). At the time of reference
      gastroscopy, the proportion of H. pylori positive patients was 38%. The presence
      of H. pylori at the time of reference gastroscopy did not correlate with ulcer
      recurrence. A recurrent. ulcer was more often found in patients with
      histologically normal gastric mucosa in the stump than in those with H. Pylori
      infection (35% and 19%, p = 0.25). CONCLUSIONS: A persistent H. pylori infection
      is frequently seen in the gastric remnant after operation for peptic ulcer
      disease, but the infection does not seem to cause ulcer relapses in the gastric
      stump or in the anastamosis.

PMID- 9638458
TI  - Results of resection of gastric cancer with distant metastases.
AB  - BACKGROUND/AIMS: The present study was carried out in order to examine the
      outcome of resection in cases of gastric cancer with distant metastases.
      METHODOLOGY: The survival rates of two hundred and eighty-one patients who had
      undergone resection for primary carcinomas of the stomach, and who had distant
      metastases according to the TNM classification, were studied. RESULTS: The 5-year
      survival rates for patients with metastasis to the peritoneum or group 3 nodes
      were 8.9% and 15.3% respectively and were significantly higher than the survival
      rates for patients with metastasis to the liver (0%), to group 4 nodes (2.2%) or
      to more than one site among the liver, lymph nodes and peritoneum (3.5%).
      Moreover, the 5-year survival rates for patients with metastasis to the
      peritoneum and N3 nodes increased significantly to 29.4% and 24.2%, respectively,
      when curative surgery was performed. CONCLUSIONS: The findings of the present
      study suggests that metastases to the adjacent peritoneum or group 3 nodes have a
      greater chance of being cured using radical surgery, and that gastrectomy with
      extended lymphadenectomy (D2-D3) may be used for advanced gastric cancer if there
      is no gross evidence of metastasis to the distant peritoneum, liver or group 4
      nodes.

PMID- 9638459
TI  - Intraoperative enteroscopy in obscure gastrointestinal hemorrhage.
AB  - Forty three patients were diagnosed to have obscure gastrointestinal hemorrhage
      (OGH) between January 1987 and April 1996. Pre-operative diagnostic
      investigations were useful in localizing the site of bleeding in 28 patients
      (65.1%). These included small bowel enema (n = 12), erythrocyte tagged scan (n =
      8), Meckel's scan (n = 2) and selective visceral angiography (n = 7). Following
      complete evaluation all patients underwent exploratory laparotomy. At laparotomy
      31 patients were found to have gross lesions. Intraoperative enteroscopy (IOE)
      could detect lesions in 9 of the remaining 12 patients.

PMID- 9638460
TI  - The duodenal diverticulum: an exceptional site of massive bleeding.
AB  - Duodenal diverticula are usually asymptomatic but may induce major hemorrhage on
      rare occasions. When endoscopy cannot determine the cause of bleeding,
      angiography must be performed. This paper describes a patient in whom angiography
      identified the diverticulum as the bleeding source, which was an exceptional
      occurrence, and thereby allowed prompt, appropriate treatment.

PMID- 9638461
TI  - Gastric antral vascular ectasia (the watermelon stomach): a brief case report.
AB  - Herein, the endoscopic and histological features of a case of gastric antral
      vascular ectasia (watermelon stomach) occurring in a 76-year-old woman are
      described. The condition, first recognized by Jabbari et al in 1984, is a rare
      but important cause of severe gastrointestinal blood loss and chronic iron
      deficiency anemia. Differential diagnosis from portal hypertensive gastropathy,
      treatment and outcome of the watermelon stomach are discussed.

PMID- 9638462
TI  - Current status and future challenges of tympanoplasty.
AB  - Four decades after the introduction of tympanoplasty, the goal of achieving
      stable and long-term hearing improvement after tympanoplasty surgery for chronic
      otitis media continues to be elusive. In this review, we focus on the current
      status of our understanding of the mechanics and pathology of the middle ear
      after tympanoplasty surgery. We also analyze some problems and challenges faced
      by clinicians and basic scientists in the quest for improved postoperative
      hearing results.

PMID- 9638463
TI  - Long-term rail stance training in healthy young adult women.
AB  - Daily rail stance training was performed for no longer than 3 months on 12
      healthy Japanese women volunteers with eyes open and closed. Rail width
      conditions were varied, during which time rail stance was repeated 30 times every
      day until volunteers could stand for 60 s in at least half the trials.
      Prolongation of stance time and retention of training effects were investigated.
      The rate of progress depended on the difficulty of the stance and was determined
      by rail width and visual conditions. However, marked differences were seen among
      subjects even under the same training conditions. The faster the progress, the
      better preserved was the training effect during the post-training period. There
      was no obvious difference in the learning curve between narrow rails with eyes
      open and wide rails with eyes closed. We concluded that the retention of the
      training effect parallels the rate of progress, and this is determined by the
      difficulty of action relative to the inherent ability of the subjects.

PMID- 9638464
TI  - Cytochemical and patch-clamp studies of calcium influx through voltage-dependent
      Ca2+ channels in vestibular supporting cells of guinea pigs.
AB  - To clarify whether or not vestibular supporting cells have voltage-dependent Ca2+
      channels, cytochemical and patch-clamp studies were performed using cells
      isolated from the ampullae of the semicircular canal of the guinea pig. Image
      analysis used fura-2 as a Ca(2+)-sensitive fluorescence dye and showed that the
      intracellular Ca2+ concentration ([Ca2+]i) increased with bath application of
      high (150 mM)K+, but was unaffected by 80 mM K+. The increase in [Ca2+]i induced
      by high K+ was completely blocked by 1 microM nifedipine as an L-type Ca2+
      channel antagonist. In the patch-clamp whole-cell recording of the isolated
      supporting cells, the voltage-dependent inward current was induced by a
      depolarizing pulse lasting 2 s in a high (50 mM) Ca2+ and tetraethylammonium
      containing external solution replaced by choline chloride and a Cs(+)-containing
      internal solution. The inward current was obtained when the membrane was
      depolarized to -50 mV and maximum current was observed at -10 to +10 mV. This
      inward current was completely blocked by 1 microM nifedipine. These findings
      strongly suggest that voltage-dependent Ca2+ channels exist in the vestibular
      supporting cells and regulate Ca2+ concentration in the vestibular endolymph.

PMID- 9638465
TI  - Hearing in the MRL/lpr mouse as a possible model of immune-mediated sensorineural
      hearing loss.
AB  - In order to clarify the possible mechanism of hearing loss in immune-mediated
      sensorineural hearing loss, basic research needed includes animal model studies.
      In the present investigation, we examined hearing thresholds and cochlear
      histologies of the MRL/lpr mouse which is now well-known as a model for pathology
      consistent with systemic lupus erythematosis (SLE). Present findings demonstrated
      that there were no statistically significant differences in auditory brainstem
      response (ABR) thresholds between 4- to 6-week-old "young" and 20- to 25-week-old
      "old" MRL mice. These differences were not sex-dependent. Under light microscopy,
      there were no abnormal morphological findings in the cochleas of either young or
      old MRL mice. With immunohistochemistry, mouse IgG was detected around the
      capillary walls in the stria vascularis in both young and old MRL mice. Serum IgG
      level of the MRL mice significantly decreased after predonisolone (PSL)
      administration. However, expression of mouse IgG in the stria vascularis was not
      observed in the MRL mice after PSL administration. From these results, we
      speculate that the hearing of the MRL mouse does not always deteriorate, and the
      deposition of mouse IgG on the capillary wall in the stria vascularis is not a
      sufficient factor to induce hearing loss. At this point, we conclude that the MRL
      mouse should not be considered a useful model for immune-mediated sensorineural
      hearing loss.

PMID- 9638466
TI  - In vitro measurements of aerodynamic characteristics of an improved tracheostoma
      valve for laryngectomees.
AB  - Tracheostoma valves are often required in the rehabilitation process of speech
      after total laryngectomy. Patients are thus able to speak without using their
      hands to close the tracheostoma. The improved Groningen tracheostoma valve
      consists of a "cough" valve with an integrated ("speech") valve, which closes for
      phonation. The cough valve opens as the result of pressure produced by the lungs
      during a cough. The speech valve closes by the airflow produced by the lungs,
      thus directing air from the lungs into the esophagus at a deliberately chosen
      moment. An experimental setup with a computer-based acquisition program was
      developed to measure the pressure at which the cough valve opened and the flow at
      which the speech valve closed. In addition, the airflow resistance coefficient of
      the tracheostoma valve was defined and measured with an open speech valve. Both
      dry air from a cylinder and humid expired air were used. Results showed a
      pressure range of 1-7 kPa to open the cough valve and a flow range of 1.2-2.7 l/s
      to close the speech valve. These values were readily attained during speech,
      while the flow range occurred above values reached in quiet breathing. The device
      appeared to function well in physiological ranges and was optimally adjustable to
      an individual setting. No significant differences were measured between air from
      a cylinder and humid expired air. Findings showed that methods used to obtain
      results could be employed as a reference method for comparing aerodynamic
      characteristics of tracheostoma valves.

PMID- 9638467
TI  - Endolaryngeal high-frequency ultrasound.
AB  - High-frequency ultrasound can provide high-resolution imaging for diagnosing
      diseases of the head and neck. Over the last few years, a virtual technical
      evolution has led to the development of small and flexible ultrasound transducers
      with even greater anatomic resolution. The aim of the present study was to
      evaluate the efficacy of this new technique for imaging normal and altered
      anatomical structures of the endolarynx. Specially developed high-resolution,
      real-time ultrasound transducers (10 and 20 MHz) placed on the tip of endoluminal
      catheters were inserted into 20 autopsied larynges and five laryngectomy
      specimens. In a standardized examination process the endolarynx was analyzed in a
      real-time mode. Using this technique, exact 360 degrees cross sections of the
      larynx were obtained, demonstrating that it was possible to image the structures
      of the endolarynx with ultrasonography. Depending on the frequency used, all
      anatomical structures could be visualized up to a depth of 2 cm. In laryngeal
      cancer the depth of tumor as well as its relationship to the laryngeal framework
      could be clearly recognized. These findings suggest that this new endoluminal
      sonographic procedure represents a potentially important diagnostic tool in the
      assessment of laryngeal carcinoma.

PMID- 9638468
TI  - Diffuse idiopathic skeletal hyperostosis causing obstructing laryngeal edema.
AB  - Diffuse idiopathic skeletal hyperostosis (DISH), or ankylosing hyperostosis
      ("Forestier's disease"), is an ossifying diathesis of unknown etiology. Diagnosis
      is primarily radiologic: osseous bridging of at least four contiguous vertebral
      bodies, a radiolucent line between the deposited bone and the anterior vertebral
      surface, large osteophytes and preservation of disk height especially in the
      cervical and lumbar spine. Although DISH is found in 6-12% of autopsy cases,
      clinical features are rare and consist primarily of swallowing disorders. A case
      of DISH is reported in which excessively enlarged cervical osteophytes led to
      edema of the laryngeal inlet and consequent severe dyspnea, necessitating
      emergency tracheotomy. Surgical excision of the osteophytic masses resulted in
      relief of symptoms. Symptomatology, radiographic features and individual
      treatments are discussed, with the latter dependent on clinical symptoms.

PMID- 9638469
TI  - Anatomic relationships between surgical landmarks in type b and type c
      infratemporal fossa approaches.
AB  - Anatomic relationships of the structures exposed in type B and C infratemporal
      fossa approaches were studied in 20 temporal bones. The intrapetrous carotid
      artery (ICA), cochlea (CH), eustachian tube (ET), foramen spinosum (FS), foramen
      ovale (FO) and anterior foramen lacerum (AFL) were exposed by drilling of the
      glenoid fossa and base of middle cranial fossa. The relationships of the ICA with
      the cochleariform process (CP), CH, ET, FS, FO and AFL were noted along with
      associated measurements. The CP was lodged at a mean distance of 9.2 mm from the
      ICA genu. The ET was found to intersect the ICA. The mean distance of the ICA to
      the CH was 1.6 mm. The carotid canal was dehiscent on its horizontal portion in
      30% of the bones studied and on its vertical portion in 5%. The periarterial
      venous plexus was found in 70% of the bones. No obvious branch was observed
      emerging from the vertical portion of the ICA. The FS was found to be a canal
      having a mean length of 5.8 mm.

PMID- 9638471
TI  - Tortuous common carotid artery encountered during neck dissection.
AB  - Anomalies of the carotid artery are rare in clinical experience. To our knowledge
      a tortuous common carotid artery with an abnormal course encountered during neck
      dissection has never been reported in the available world literature. During
      dissection of the lower neck in a 60-year-old Korean man, a tortuous right common
      carotid artery was found to cross over the lower cervical trachea anteriorly and
      then was positioned in its usual site in the carotid sheath in the mid-neck.

PMID- 9638470
TI  - Flow cytometric analysis of DNA content and Ki-67-positive fractions in the
      diagnosis of salivary gland tumors.
AB  - To explore the utility of flow cytometry (FCM) for the diagnosis of
      histopathology of salivary gland tumors, fresh materials taken at surgery from 23
      Warthin's tumors, 57 pleomorphic adenomas, and 14 malignant tumors were analyzed
      for DNA ploidy and proliferative cell activities, including S-phase fraction
      (SPF), G2- plus M-phase fraction (G2M), and Ki-67-positive fraction. To
      facilitate this study, glands were taken from all major salivary sites and minor
      glands in the head and neck. DNA aneuploidy was not detected in the benign
      tumors. Nine of 14 malignant tumors showed DNA aneuploidy. The percentage of SPF
      or G2M of the malignant tumors was significantly higher than those of the benign
      tumors. The percentage of Ki-67-positive fraction of pleomorphic adenomas was
      comparable to that of malignant tumors and was significantly higher than that of
      Warthin's tumors. Ki-67 of 20% as a cut-off had a sensitivity of 88%, specificity
      of 100%, and accuracy of 91% for differentiating pleomorphic adenomas from
      Warthin's tumors. In analyzing DNA content and proliferative activities by FCM,
      we could distinguish among the three major histopathologies of salivary gland
      tumors. Warthin's tumors showed low SPF + G2M with low Ki-67, pleomorphic
      adenomas had low SPF + G2M with high Ki-67, and malignant tumor showed high SPF +
      G2M with high Ki-67. The high percentage of the Ki-67-positive fraction seen in
      pleomorphic adenomas may reflect their potential biological aggressiveness
      manifested as tumor recurrence or malignant transformation.

PMID- 9638472
TI  - A murine model system for detection of neoplasia of the head and neck using
      transfectomas and carcinoembryonic antigen transgenic mice.

PMID- 9638473
TI  - Heterogeneity in the clonal T cell response. Implications for models of T cell
      activation and cytokine phenotype development.
AB  - The T cell can be defined in the context of two properties--the recognition
      specificity of the T cell receptor (TCR) heterodimer and the functional response
      of the T cell after TCR stimulation. Once a particular TCR heterodimer is
      expressed and successfully selected during thymic development, the antigen
      specificity is fixed for all the clonal progeny of that cell. In contrast, the
      potential functional responses that may be generated in response to specific
      antigen in the postthymic environment are quite extensive. These range from
      programmed cell death to initiation of alternate programs of phenotype
      development that generate effector populations with distinct cytokine expression
      patterns and regulatory properties. Recent advances in analytical methods that
      have permitted multiparametric characterizations of the T cell response at the
      single cell, rather than population level, have necessitated a modified view of T
      cell activation and the clonal T cell response, and have generated new insights
      into the regulation of immunity. In this brief review, we highlight studies that
      have characterized heterogeneity of the CD4+ T cell clonal response based on
      single-cell analyses, and discuss implications for models of T cell activation
      and cytokine phenotype development.

PMID- 9638474
TI  - Regulation of adaptive immunity by natural killer cells.
AB  - Natural killer (NK) cells are well recognized as cytolytic effector cells of the
      innate immune system. In the past several years, the structure and function of NK
      cell receptors for the major histocompatibility complex (MHC) class I molecules
      and other ligands have been the subject of extensive studies. These studies.
      These studies have focused largely on the mechanisms of target cell recognition
      for lysis. Another aspect of NK cell function that seems to be underappreciated
      is their role in immune regulation. Since NK cells produce a number of
      immunologically relevant cytokines, it has been suggested that these cells may
      modulate the development of the adaptive immune response. But, is it the only
      mechanism by which NK cells interact with cells involved in the induction of
      antigen-specific responses? This article reviews some older and more recent
      studies and attempts to place NK cells in the context of potent immune regulators
      of T cell responses.

PMID- 9638475
TI  - The intercellular adhesion molecule (ICAM) family of proteins. New members and
      novel functions.
AB  - Macromolecular adhesive associations between cells are important for transmitting
      spatial and temporal information that is critical for immune system function. One
      such group of proteins, the intercellular adhesion molecules (ICAMs), has grown
      as newly identified members are revealed. In addition, the functions of the
      ICAMs, in general, have begun to be better understood, including intracellular
      signaling events. This information has led to the design of novel therapeutic
      agents that may prove effective in a variety of disease states.

PMID- 9638478
TI  - Cytological changes and conjunctival hyperemia in relation to sensory eye
      irritation.
AB  - In general, irritation is a physiological response to a chemical or physical
      stimulus involving objective changes (e.g., local redness and edema) and
      subjective sensations (e.g., pruritus and pain). The perception of an irritating
      stimulus in the eyes and the upper airways is called sensory irritation. Sensory
      irritation is a prevalent symptom in relation to complaints about indoor air
      quality. The intensity of perceived sensory irritation in humans has mainly been
      evaluated using psychophysical methods. However, perceived sensory irritation is
      dependent on the subject expressing the symptoms; that is, it is a subjective
      measure. This is a problem in assessment of irritation effects from air pollution
      or other factors, since the expression of the irritation symptoms may be biased
      by, for example, interaction with other people and odors. The subjectivity of the
      measures is an important complication in several studies dealing with problems
      regarding indoor air quality. The bias problems make it important to complement
      the psychophysical measurements of sensory irritation with objective assessments
      of irritation. In addition, only little is known about the association between
      sensory irritation and possible physiological/ pathological changes in the
      mucosal membranes in relation to studies of indoor air. Two studies (study 1 and
      study 2) were conducted to investigate changes in conjunctival hyperemia and
      conjunctival fluid cytology for subjects exposed to volatile organic compounds
      (VOCs) in their eyes only. Eight subjects participated in study 1. Each subject
      was exposed to three different mixtures of VOCs. A total of 16 subjects
      participated in study 2. Half of the subjects were exposed to 1-octene and the
      other half, to n-butanol. In both studies, photographs of bulbar conjunctiva were
      taken and conjunctival fluid was sampled before and after exposure. Moreover, the
      perceived irritation intensities were registered continuously during exposure.
      Overall, perceived irritation intensity and conjunctival hyperemia increased with
      increasing exposure concentrations, whereas cytological changes in the
      conjunctival fluid samples did not seen to be related to exposure concentration,
      perceived irritation, or changes in conjunctival hyperemia.

PMID- 9638476
TI  - The role of germinal centers for antiviral B cell responses.
AB  - Germinal centers (GCs) are crucially involved in T cell-dependent B cell
      responses. B cells rapidly proliferate within GCs and their Ig variable region
      genes undergo hypermutation. Cognate T helper cells and antigen presented in
      native form on follicular dendritic cells (FDCs) select B cells expressing high
      affinity Igs, leading to affinity maturation and the generation of memory B
      cells. In addition to these well-established functions of GCs, this article
      presents evidence that they also play a crucial role for the maintenance of
      specific memory Ig titers and for the prevention of viral antibody escape
      mutants.

PMID- 9638479
TI  - Effects of methyl ethyl ketone, acetone, or toluene coadministration on 2,5
      hexanedione concentration in the sciatic nerve, serum, and urine of rats.
AB  - OBJECTIVE: To clarify changes in the serum, nerve, and urinary levels of 2,5
      hexanedione (2,5-HD) in rats on coadministration with methyl ethyl ketone (MEK),
      acetone (AC), and toluene (TO). METHOD: 2,5-HD alone or combined with MEK, AC,
      and TO was injected subcutaneously into a total of 306 male Wistar rats. The rats
      were divided as follows into 7 groups: (1) 2.6 mmol/kg 2,5-HD alone (HD) and (2)
      2.6 mmol/ kg 2,5-HD combined with 2.6 mmol/kg MEK (HD + MEK), (3) with 2.6
      mmol/kg AC (HD + AC), (4) with 2.6 mmol/kg TO (HD + TO), (5) with 13.0 mmol/kg
      MEK (HD + 5MEK), (6) with 13.0 mmol/kg AC (HD + 5AC), and (7) with 13.0 mmol/kg
      TO (HD + 5TO). 2,5-HD concentrations in the serum, sciatic nerve, and urine of
      rats were determined within 16 h of the injections and pharmacokinetic parameters
      were estimated. RESULTS: It was observed that (1) the 2,5-HD concentration and
      AUC value (area under concentration versus time curve) determined in the serum
      and nerve increased significantly in the cotreated groups as compared with the HD
      group; (2) the effect MEK had in elevating the 2,5-HD concentration and AUC in
      the serum and nerve was stronger than that of AC, and the effect AC had was
      stronger than that of TO; (3) a. dose increase from 2.6 to 13.0 mmol/kg for MEK
      and AC induced further increases in the 2,5-HD concentration and AUC determined
      in the serum and nerve; (4) elimination constants recorded for 2,5-HD (Ke) from
      the serum and nerve decreased in all the cotreated groups, and the degree of the
      decrease correlated inversely with the elevation in 2,5-HD concentration and AUC
      in the serum and nerve; and (5) urinary 2,5-HD concentrations measured in the
      13.0-mmol/kg cotreated groups increased in parallel with the elevation in serum
      2,5-HD concentrations. CONCLUSION: Coadministration of 2,5-HD with MEK, AC, or TO
      can increase the concentration and AUC of 2,5-HD in serum and the sciatic nerve,
      and these increases can be further enhanced by an increase in the concomitant
      doses of MEK and AC.

PMID- 9638480
TI  - Update of cancer incidence among workers at a copper/nickel smelter and nickel
      refinery.
AB  - OBJECTIVES: To assess cancer risk among nickel-exposed workers. METHODS: We
      updated cancer incidence among 1388 workers employed for at least 3 months at a
      copper/nickel smelter and nickel refinery in Harjavalta, Finland. There were 1155
      workers exposed to nickel during the period 1960-1985 in the smelter (566
      workers), repair shop (239 workers), or refinery (418 workers). Cancer incidence
      was followed through the files of the Finnish Cancer Registry up to 31 December
      1995. For overall cancer and for a priori selected specific cancer types the
      ratio of observed to expected numbers of cases was computed as a standardized
      incidence ratio (SIR), controlled for age, gender, and calendar period and using
      the region-specific rates as a reference. RESULTS: The overall cancer incidence
      among both nickel-exposed and unexposed subcohorts was at the expected level. A
      small increase in lung cancer incidence, which reached statistical significance
      among workers with a latency exceeding 20 years, was observed among the smelter
      workers exposed to insoluble nickel compounds. Among workers in the refinery, who
      were exposed primarily to nickel sulfate at levels below 0.5 mg/m3 as well as to
      low concentrations of other nickel compounds, there was an increased risk for
      nasal cancer (SIR 41.1, 95% CI 4.97-148), positively associated with latency and
      duration of employment, and an excess risk for stomach (SIR 4.98, 95% CI 1.62
      11.6) and lung (SIR 2.61, 95% CI 0.96-5.67) cancers. CONCLUSIONS: Since elevated
      nasal and lung cancer risks were confined to the refinery, where the primary
      exposure was to nickel sulfate, it is likely that nickel sulfate is mainly
      responsible for the elevated respiratory cancer risk. We cannot rule out whether
      the excess stomach cancer risk is a chance finding, or related to the working
      environment.

PMID- 9638477
TI  - Thymopentin and splenopentin as immunomodulators. Current status.
AB  - Splenopentin (SP-5, Arg-Lys-Glu-Val-Tyr) and thymopentin (TP-5, Arg-Lys-Asp-Val
      Tyr) are synthetic immunomodulating peptides corresponding to the region 32-34 of
      a splenic product called splenin (SP) and the thymic hormone thymopoietin (TP),
      respectively. TP was originally isolated as a 5-kDa (49-amino acids) protein from
      bovine thymus while studying effects of the thymic extracts on neuromuscular
      transmission and was subsequently observed to affect T cell differentiation and
      function. TP I and II are two closely related polypeptides isolated from bovine
      thymus. A radioimmunoassay for TP revealed a crossreaction with a product found
      in spleen and lymph node. This product, named splenin, differs from TP only in
      position 34, aspartic acid for bovine TP and glutamic acid for bovine splenin and
      it was called TP III as well. Synthetic pentapeptides (TP-5) and (SP-5),
      reproduce the biological activities of TP and SP, respectively. It is now evident
      that various forms of TPs were created by proteolytic cleavage of larger proteins
      during isolation. cDNA clones have been isolated for three alternatively spliced
      mRNAs that encodes three distinct human T cell TPs. The immunomodulatory
      properties of TP, SP, TP-5, SP-5 and some of their synthetic analogs reported in
      the literature have been briefly reviewed.

PMID- 9638481
TI  - Evaluation of urinary cadmium and lead as markers of background exposure of
      middle-aged women in Korea.
AB  - OBJECTIVE: The present study was initiated to investigate the validity of cadmium
      (Cd) and lead (Pb) in urine in comparison with the metals in blood as a
      biological marker of nonoccupational exposure of general populations to these
      metals as environmental pollutants. DESIGN: Peripheral blood samples, morning
      spot-urine samples, and 24-h total food duplicate samples were collected from 107
      nonsmoking women (aged 30-59 years) in four urban and rural survey sites in
      Korea. METHODS: Portions of the samples were digested by heating in the presence
      of mineral acids, and the digests were analyzed for Cd and Pb by graphite furnace
      atomic absorption spectrophotometry. The metal concentrations in urine were
      adjusted for creatinine concentration and a specific gravity of 1.016. The
      analyte levels were evaluated on an individual basis (n = 107) and also on a
      group basis, i.e., in terms of geometric means for the survey sites (n = 4).
      RESULTS: Cd in urine correlated with Cd in blood on an individual as well as
      survey-site basis and tended to correlate with Cd in food duplicates on a group
      basis. The correlation of Pb in urine with Pb in blood was weaker than that of Cd
      in urine with Cd in blood when evaluated on an individual and survey-site basis.
      Pb in urine correlated with Pb in food duplicates either weakly or even
      negatively when examined on a survey-site basis. CONCLUSIONS: Cd in urine proved
      to be valid as a biological marker of environmental exposure of general
      populations, whereas less support was obtained for Pb in urine as an exposure
      marker.

PMID- 9638482
TI  - Erythrocyte antioxidant enzyme activities in coal miners from three French
      regions.
AB  - This study investigated whether differences in the prevalence and severity of
      coal workers' pneumoconiosis (CWP) between three coal mines could be related to
      differences in oxidative stress exposure as evaluated in vivo through red-blood
      cell antioxidant enzyme activities. Blood samples were obtained from 229 miners
      selected according to their occupation and their pneumoconiotic status. The
      following biomarkers were evaluated: erythrocyte catalase, Cu2+/Zn2+ superoxide
      dismutase (Cu2+/Zn2+ SOD), and glutathione peroxidase activities. Antioxidant
      enzyme activities did not differ significantly between the group of surface
      workers in Lorraine and the group of underground miners without CWP in Lorraine
      and in the other coal mines. Erythrocyte Cu2+/Zn2+ SOD activity was slightly
      decreased in the group of active underground miners with simple pneumoconiosis as
      compared with the group of miners without CWP in Nord/Pas-de-Calais. No effect
      was seen between retired miners at different stages of CWP. Our findings indicate
      that differences in the prevalence and severity of CWP do not seem to be related
      to various oxidative activities of coal dust particles, at least as reflected by
      measurements of antioxidant enzyme activities in circulating erythrocytes in this
      study.

PMID- 9638483
TI  - Angular and fibrous particles in lung in relation to silica-induced diseases.
AB  - INTRODUCTION: The lung concentration of angular and fibrous particles was
      measured in cases of lung fibrosis only, in cases of lung fibrosis and lung
      cancer, and in cases of lung cancer only. These patients worked in different
      trades (mining, foundries, construction and were not a homogeneous group of
      exposed workers. MATERIAL AND METHODS: Particles, both angular and fibrous, were
      extracted from lung parenchyma by a bleach digestion method, mounted on copper
      microscopic grids by a carbon replica technique, and analyzed by transmission
      electron microscopy (TEM) and energy-dispersive spectroscopy (EDS). The quartz
      concentration was also determined by X-ray diffraction (XRD) on a silver membrane
      filter after extraction from the lung parenchyma. RESULTS: (1) Lung cancer and
      lung fibrosis cases retained more metal-rich particles (P = 0.02) and more
      angular particles of all sorts (P = 0.009) than did lung fibrosis cases only, and
      the differences were statistically significant. (2) However, more quartz was
      retained in the lungs in lung fibrosis cases than in lung fibrosis or lung cancer
      cases, but the difference in the concentrations was not statistically
      significant. (3) More ferruginous bodies were retained in the lungs in lung
      cancer and lung fibrosis cases than in cases of lung fibrosis only, and the
      difference in the concentrations was statistically significant (P = 0.02).
      CONCLUSION: Results obtained from lung tissue must always be interpreted
      cautiously. However, these results are consistent with the hypothesis that
      workers in some trades such as foundries were exposed not only to quartz but also
      to asbestos, ceramic fibers, metal-rich non fibrous particles, and other likely
      carcinogenic chemicals. The wide range of particle types identified in the lungs
      of these workers illustrates the complexity of trying to determine disease
      origins in these work environments. Epidemiology studies have to control for the
      exposure to these carcinogens as well as for smoking habits.

PMID- 9638484
TI  - Neurological and functional effects of short-term exposure to hand-arm vibration.
AB  - OBJECTIVE: The aim of the present study was to quantify the sensory and
      functional effects resulting from a short-duration (30 min) exposure to hand-arm
      vibration. SUBJECTS AND METHODS: Nine subjects went through nine laboratory
      experiments. For 32 min they grasped a handle vibrating at three different
      amplitudes (5, 20, and 80 ms-2) and at three frequencies (31.5, 125, and 500 Hz).
      Additionally, a reference experiment was conducted in which the handle did not
      vibrate. Three sensory tests [vibration perception threshold (VPT), pressure
      perception threshold (PPT), and distal sensory latency time (DSL)], two
      functional tests [Purdue peg-board (PPB) and maximal voluntary force (MVF)], and
      a questionnaire concerning the perceived paresthesia and numbness were completed
      before, during, and after exposure. RESULTS: A 32-min period of exposure to
      vibration leads to a temporary threshold shift (TTS) of the VPT and to the
      development of paresthesia and numbness. The VPT appears to vary with the
      exposure duration according to a first-order model with a time constant about
      equal to 3 min. The TTS increases with the vibration acceleration amplitude and
      is greater for an exposure frequency of 125 Hz than for that of 31.5 or 500 Hz.
      It is also greater at the test frequency 125 Hz than at 31.5 Hz. The other tests
      do not demonstrate any significant variation. In particular, the PPB test does
      not demonstrate any loss of dexterity. CONCLUSION: After some 30 min of exposure
      to vibration the VPTs are increased and paresthesia and numbness develop.
      However, these do not appear to influence significantly the capacity or
      performance at work.

PMID- 9638485
TI  - Benzene exposure in car mechanics and road tanker drivers.
AB  - The purpose of this study was to identify professional factors related to benzene
      exposure and to deduce suitable safety measures. Atmospheric benzene, urinary
      muconic acid (tt-MA) and leukocyte alkaline phosphatase activity (LAPA) were
      evaluated among 66 car mechanics, 34 road tanker drivers, and 28 nonexposed
      workers. Professional and medical questionnaires were filled in at the same time.
      Atmospheric benzene was significantly higher among road tanker drivers than among
      car mechanics. The arithmetic mean +/- SD, median, and geometric mean values
      were, respectively, 0.48 +/- 1.49, 0.14, and 0.06 mg/m3 among car mechanics and
      1.88 +/- 4.18, 0.68, and 0.65 mg/m3 among road tanker drivers. In the latter case
      the increase was caused by transport of unleaded petrol and correlated with the
      volume of the tank. Among car mechanics, tobacco smoking, windy conditions,
      dismantling of petrol filters, and handling of petrol increased atmospheric
      benzene levels. Urinary muconic acid was increased significantly among car
      mechanics (148 +/- 137, 127, and 111 micrograms/g) and among road tanker drivers
      (309 +/- 420, 137, and 151 micrograms/g) as compared with the controls (49 +/-
      46, 33, and 33 micrograms/g). Among road tanker drivers, alcohol intake and
      transportation of unleaded petrol increased the excretion of muconic acid, which
      was also directly related to the volume of the tank. Among car mechanics,
      professional factors (dismantling of petrol filters, handling of and washing of
      hands with petrol) and nonprofessional factors (tobacco smoking and damaged skin
      on the hands and forearms) increased muconic acid excretion. In the control
      group, tobacco smoking increased its excretion. LAPA was not significantly
      modified among exposed workers. There was a weak but significant linear
      correlation between LAPA and muconic acid. These results suggest that to reduce
      exposure to benzene in unleaded petrol, individual and collective safety measures
      should be imposed in both occupations.

PMID- 9638486
TI  - Determination of urinary 2,5-hexanedione in the general Italian population.
AB  - OBJECTIVE: Determination of the urinary levels of 2.5-hexanedione (2,5-HD) was
      performed in subjects belonging to the Italian general population to define the
      reference value for this metabolite. MATERIALS AND METHODS: Urine samples were
      collected from 123 healthy Italian subjects who had not been occupationally
      exposed to n-hexane or methyl-n-butyl ketone (60 men and 63 women; 53 living in
      urban areas and 70 living in rural areas; 36 smokers and 87 nonsmokers; 65 aged
      above 35 years and 58 aged below 35 years). The determinations were performed by
      a gas chromatography method using a flame ionization detector (FID). A quality
      control step was realized by analysis of 78 of these samples by high-performance
      liquid chromatography (HPLC) with UV detection. RESULTS AND DISCUSSION: The
      distribution of 2,5-HD concentration was log-normal and the corresponding
      centiles at the 95% confidence interval were as follows: the 50th centile, 0.270
      mg/l for men and 0.191 mg/l for women; the 75th centile, 0.352 and 0.330 mg/l,
      respectively, for men and women; and the 95th centile, 0.762 and 0.582 mg/l,
      respectively, for men and women. The reference value, calculated as the upper
      unilateral 95% tolerance interval at 95% of confidence, was 0.795 mg/l for men
      and 0.627 for women.

PMID- 9638487
TI  - Occupational protein contact dermatitis with type I allergy to different kinds of
      meat and vegetables.
AB  - OBJECTIVE: Even though occupational protein contact dermatitis is not an uncommon
      finding in occupational dermatology, reports about multiple sensitizations are
      rare. High-molecular-weight substances such as proteins can pass the epidermis
      only if it is damaged and cause a sensitization. In a high percentage of case,
      atopic dermatitis might be the cause of this damage but cannot be regarded as the
      only cause. An interesting case is presented that was carefully worked up.
      METHODS: Scratch, intracutaneous, and prick or prick-to-prick tests with native
      occupational allergens were performed as single tests. The patient was patch
      tested with the European Standard Series. The determination of allergen-specific
      IgE was performed by ImmunoCAP. The results were subdivided into six classes. In
      addition, oral provocations with relevant allergens were performed. RESULTS: The
      skin tests showed positive type I allergies to beef, lamb, horse, and pork meat,
      to pork and horse blood as well as to rye and wheat flour, raw potato, and pasta.
      Weak positive reactions could be found for fowl, duck, goose, and turkey in
      intracutaneous testing. The ImmunoCAP showed elevated specific IgE values for
      pork meat, raw potato, and rye and wheat flour. The oral provocation did not show
      any systemic or skin change. CONCLUSIONS: This case report demonstrates how an
      initial case of contact urticaria turns into protein contact dermatitis. It shows
      that the diagnosis can be made by means of scratch or prick tests with native
      occupational allergens. The determination of allergen-specific IgE by ImmunoCAP
      might be helpful, but a negative result does not exclude protein contact
      dermatitis.

PMID- 9638490
TI  - Clinical and manometric effects of combined external beam irradiation and
      brachytherapy for anal cancer.
AB  - This study evaluates anorectal function after combined tele- and brachytherapy
      for anal cancer using manometric measurements and a standardized questionnaire.
      Eight patients received 44 +/- 3 Gy external beam radiation followed by 20 +/- 4
      Gy interstitial brachytherapy with iridium-192. Patients were examined 43 months
      (range 25-83) after therapy. Maximum anal basal pressure, squeeze pressure, and
      squeeze increment were significantly lower in patients (50, 163, 115 mmHg,
      respectively) than in control subjects (75, 285, 180 mmHg, respectively).
      Decreased anal elasticity was not observed. Anal prestretch "normalized" the
      contractility of the internal and external sphincter. Thus damage to the anal
      epithelium and hemorrhoidal cushions seems to be the most important mechanism
      explaining reduced anal closing pressure values. The rectoanal inhibitory reflex
      was observed in all but one patient. Rectal compliance was significantly reduced.
      Whereas all patients could retain a water filled rectal balloon until the maximum
      tolerable sensation level was reached, the rectal saline infusion test was
      strongly abnormal. Four patients were perfectly continent. Four patients were
      incontinent for gas and presented urgency in case of liquid stools with limited
      soiling occurring once weekly or less; three of them also had urgency for solids.
      Defecation frequency was increased but regular in most patients. Reduced anal
      closure together with reduced rectal compliance are at the basis of stool
      frequency, urgency and partial incontinence with occasional soiling. However,
      enough reserve sphincter function was maintained to preserve a clinically
      acceptable degree of anal continence in our patients.

PMID- 9638491
TI  - Prevalence of fecal incontinence: what can be expected?
AB  - Fecal incontinence is a serious problem especially for the elderly. The
      epidemiology of incontinence is not well described in the literature although it
      is often used as an endpoint for treatment evaluation in clinical trials.
      Complete continence is often assumed to be the "normal" standard. The goals of
      this study were to establish detailed prevalence rates for fecal incontinence in
      a standard population and to identify differences due to age and sex. A
      questionnaire about fecal incontinence and its consequences with predefined
      answers was filled out anonymously by 500 volunteers. The study population was
      selected to meet the respective age and sex distribution of the German adult
      population. The data indicated that 4.8% of the persons were unable to control
      solid stools, while 19.6% had problems at least with one type of incontinence
      (solid, pasty, or lipid stools, winds). Problems with pasty or liquid stools are
      more frequent in women. The ability to control wind is decreased in elderly
      persons. The time needed to reach a toilet is shorter for women, and generally
      decreases in the elderly. Men more often describe soiling the underwear. Persons
      with signs of incontinence show decreased levels of social activities. A global
      incontinence rate of 5% fits well with some previously published results. Soiling
      of the underwear is not well suited for defining incontinence. The increased rate
      in women may in part be explained by morphological differences. The reduced time
      to hold stools especially in the elderly in combination with a reduced mobility
      may result in a higher rate of incontinence, which is correlated with reduced
      social activities.

PMID- 9638489
TI  - Substance P containing nerve fibers in ulcerative colitis.
AB  - The distribution of and morphological changes in substance P containing nerve
      fibers were examined immunohistochemically in the colonic mucosa of ulcerative
      colitis (UC) patients. Quantitative and morphological changes in substance P
      fibers were analyzed by digitized morphometry. The linear density of substance P
      fibers was significantly greater in the UC group (19.4 +/- 1.2 microns/1000
      micron 2) than in the Crohn's disease group (10.1 +/- 1.2 microns; P < 0.01) and
      the control group (8.4 +/- 0.8 microns; P < 0.01). Analysis of the UC group
      showed that the degree of inflammation affected the linear density of substance
      fibers, with "moderate" cases presenting the highest linear density and "severe"
      cases the lowest. Substance P fibers were thickened and coarse in UC; they were
      significantly wider in the UC group (2.5 +/- 0.5 microns) than in the Crohn's
      disease group (1.5 +/- 0.2 microns; P < 0.01) and the control group (1.2 +/- 0.1
      microns; P < 0.01). In conclusion, alterations in substance P containing nerve
      fibers, as evidenced by both the linear density and morphology, may play some
      role in the pathogenesis of UC.

PMID- 9638492
TI  - New healing agent for colonic anastomosis.
AB  - This study evaluated the healing property, on colonic anastomoses, of a new
      compound termed RGTA11 (standing for "regenerating agent," a dextran derivative
      with heparin-like properties). Colonic anastomoses were performed in 183 adult
      rats after dipping both ends of the colon in solutions containing RGTA11. The
      anastomoses were made end-to-end on a single plan, 8 sutures. Healing was
      evaluated mechanically by the bursting pressure in 108 animals and histological
      analysis in 75. Results indicated that after 48 h RGTA11-treated animals
      presented a twofold increased resistance to anastomoses breakage (P < 0.01) over
      nontreated (saline buffer) animals. After 96 h and until day 7 there was no
      longer a difference between study and control animals. Although this difference
      in breakage was not readily observed at histological level, results suggest that
      RGTA11 could be used to aid colonic anastomosis healing. RGTA11 is of potential
      clinical interest in this regard since complications that are known to occur
      postoperatively result from early leakage.

PMID- 9638495
TI  - The appropriate use of colonoscopy in the curative management of colorectal
      cancer.
AB  - A total of 175 patients who underwent a curative resection for a colonic (n =
      130) or a rectal cancer (n = 45) between 1986 and 1992 were entered into a
      routine colonoscopy program. Colonoscopies were performed 1 year after the
      operation, and then at 2-year intervals. The findings at colonoscopy, as well as
      those of preoperative colonoscopy (when performed), were recorded. Eleven
      anastomotic recurrences were diagnosed at an asymptomatic stage, at a mean follow
      up of 14 months. All of them were identified in patients with a stage B or C
      primary rectosigmoid cancer. Eight patients underwent another potentially
      curative re-operation. Only perioperative colonoscopy (preoperative colonoscopy;
      first postoperative colonoscopy in patients for whom the preoperative procedure
      was incomplete or not performed) allowed diagnosis of second cancers (n = 7) and
      adenomatous polyps greater than 10 mm (n = 17). Further colonoscopies detected
      only polyps less than 10 mm. Positive examination rates for successive follow-up
      colonoscopies were 15, 20 and 23%, respectively; they were significantly higher
      in patients who had previously had adenomatous polyps than in patients who had
      not: 30% versus 6% (P < 0.025), 46% vs 5% (P < 0.005) and 38% vs 11% (P < 0.025),
      respectively. From these data, the following recommendations are made: (1) All
      colorectal cancer patients should have a total colonoscopy either before
      (whenever possible) or soon after operation; (2) Based on results of the
      perioperative colonoscopy, patients: should undergo their first follow-up
      colonoscopy only 3 yearly (presence of synchronous adenomatous polyps) or 5
      yearly (absence of synchronous adenomatous polyps) after resection; (3) In
      patients with stage B or C primary rectosigmoid cancer, a surveillance of the
      suture line by rigid proctosigmoidoscopy should be added during the first 2
      postoperative years: 6, 15 and 24 months after the operation.

PMID- 9638494
TI  - Outcome of patients with an implanted artificial anal sphincter for severe faecal
      incontinence. A single institution report.
AB  - Implantation of an artificial sphincter is an alternative treatment for patients
      with severe faecal incontinence. This prospective study from one institution has
      evaluated the results from 13. Preoperative and postoperative incontinence
      scores, anal manometry, and quality of life were evaluated in 13 patients who had
      undergone implantation of an artificial sphincter over a 7-year period. Two
      patients were definitive failures. One developed acute total colitis after 5
      years of satisfactory function, and a second had discomfort and demanded removal
      of an otherwise functioning device. After a median follow-up of 30 (range 5-76)
      months, 11 patients had an activated and functional device. These included 6 with
      a urinary AMS 800 and 5 with the newly designed anal ABS. The mean incontinence
      score decreased from 17 to 4, and quality of life improved markedly. Two of the
      11 patients had undergone successful reimplantation, one following rupture of the
      cuff and the second following ulceration of the control pump through the labia.
      In no case was infection or erosion of the anal canal a cause of failure. While
      the cause of incontinence and age did not affect outcome, psychological reaction
      had a significant impact. The artificial anal sphincter may have a role to play
      in severe faecal incontinence.

PMID- 9638493
TI  - Transrectal ultrasonography: relationship with anorectal manometry,
      electromyography and sensitivity tests in irritable bowel syndrome.
AB  - Irritable bowel syndrome is the most frequently diagnosed disorder in
      gastroenterology. It has been demonstrated with specialized motility studies that
      these patients compared to healthy subjects show changes in rectoanal electrical
      and mechanical activity and in rectoanal sensitivity. However, until now no
      report has been published on morphological alterations in the rectum or the
      internal anal sphincter. Twenty-five consecutive patients with irritable bowel
      syndrome (mean age 32, range 17-47 years; 24 females) were evaluated
      prospectively by transrectal ultrasonography, rectal sensitivity studies, and
      recordings of both electrical and mechanical activity of the distal rectum and
      internal anal sphincter during a 2-h inter-digestive period. Ten healthy
      volunteers (mean age 34.5, range 19-50 years) served as a control group. Paired
      and non-paired Student's two-tailed t test and linear regression analysis were
      used. It was shown that muscle thickness of the rectum during rest (4.7 +/- 0.1
      mm) was correlated neither with its rectal spike amplitude (0.73 +/- 0.1 mV) nor
      with rectal spike frequency (17.06 +/- 3.6 spike/2 h). In addition, the diameter
      of the internal anal sphincter (1.2 +/- 0.1 mm) was correlated neither with its
      resting pressure, nor with frequency (17.1 +/- 3.2/2 h), duration (14.9 +/- 1.5
      s), or amplitude (14.1 +/- 1.9 mmHg), of inhibition of the spontaneous rectoanal
      inhibitory reflex. No correlation was found between ultrasonographic parameters
      and rectal distension variables (r = 0.03). This study demonstrates for the first
      time morphological anorectal changes in patients with irritable bowel syndrome
      compared to healthy subjects, in addition to showing that morphological changes
      are independent of physiological ones. Therefore both transrectal ultrasonography
      to determine anorectal morphology and electromanometry to assess anorectal
      function are important measures in the evaluation of patients with irritable
      bowel syndrome.

PMID- 9638488
TI  - Fistulas complicating diverticulitis.
AB  - This study was undertaken to assess the appropriate management of patients with
      diverticulitis complicated by fistula formation. A retrospective chart review was
      conducted on patients with symptoms of a fistula who presented between 1975 to
      1995. There were 42 patients (32 women, 76%; 10 men, 24%) who ranged in age from
      46 to 89 years (mean 69.8 +/- 9.8). Six patients had multiple fistulas. The types
      of fistulas included colovesical (48%), colovaginal (44%), colocutaneous (4%),
      colotubal (2%), and coloenteric (2%). Operative procedures consisted of resection
      and primary anastomosis in 38 patients and a Hartmann's operation in one. Three
      patients were managed conservatively with antibiotics (two due to poor
      performance status, the third due to resolution of symptoms). There were no
      operative deaths. The postoperative course was uncomplicated in 69%, while 12
      patients (31%) experienced 19 complications (40%). These consisted of urinary
      tract infection (9.5%), atelectasis (7.1%), prolonged ileus (4.8%), arrhythmias
      (4.8%) and renal failure, myocardial infarction, pseudomembranous colitis,
      peroneal nerve palsy, unexplained fever, pulmonary edema (2.4% each). There were
      no anastomotic leaks and no deaths. Hospital stay ranged from 6 to 31 days (mean
      12.3 +/- 7.6). Fistulas due to diverticulitis were safely managed by resection
      and primary anastomosis without mortality and with acceptable morbidity in this
      series. Patients deemed to be poor operative risks can be managed with a course
      of nonoperative treatment.

PMID- 9638496
TI  - The novel combination of fat clearance and immunohistochemistry improves
      prediction of the outcome of patients with colorectal carcinomas: a preliminary
      study.
AB  - To evaluate the significance of micrometastases in relation to survival rate,
      specimens from 48 colorectal carcinoma patients were analysed after fat
      clearance. The number and size of the lymph nodes harbouring metastases and the
      significance of micrometastases for patients' survival were assessed. We found
      that although the majority of metastatic lymph nodes (71.8%) were 5 mm or less in
      diameter, their size had no effect on survival. Immunohistochemical staining of
      lymph nodes revealed that 15 of 25 patients with Dukes' stage B diagnosed by
      routine staining had micrometastases, 86% of these lymph nodes being less than 5
      mm in diameter. The survival rate of this subgroup was found to be considerably
      poorer than that of Dukes' stage B patients with no micrometastases. None of the
      three patients with Dukes' stage A carcinoma had micrometastases. Since most of
      the metastases and micrometastases occur in lymph nodes of 5 mm and less and can
      be easily missed by routine examination, we suggest that fat clearance and
      routine immunohistochemical analysis of Dukes' stage B improve the prediction of
      outcome of colorectal cancer patients.

PMID- 9638497
TI  - Patterns of distribution of endoscopic and histological changes in the ileal
      reservoir after restorative proctocolectomy for ulcerative colitis. A long-term
      follow-up study.
AB  - OBJECTIVE: This study was undertaken to assess the long-term macroscopic
      appearance of the ileal reservoir after restorative proctocolectomy for
      ulcerative colitis, to determine whether there is any correlation between
      macroscopic and histological changes and whether the distribution of these is
      homogeneous, focal or patchy. BACKGROUND: No study has examined the macroscopic
      appearance of the ileal reservoir over a long period and it is still unknown to
      what degree histological changes are diffuse or patchy. Moreover, the
      relationship between macroscopic and histological changes is poorly understood.
      METHOD: Fifty-nine patients were examined by one clinician (PSC) 5.3-14.5 years
      (median 8.2 years) postoperatively. A rigid sigmoidoscopy of the reservoir was
      performed. Four zones in the posterior midline at 5-cm intervals from the
      ileoanal anastomosis were inspected. At each level a macroscopic score of
      severity of inflammation was given and a biopsy taken. The degree of acute and
      chronic inflammation was assessed using a histopathological scoring system.
      RESULTS: All reservoirs showed macroscopic abnormalities, which were more marked
      distally in 14 (24%). There was no case in which severity of inflammation was
      greater in proximal than in distal zones. Endoscopy overall correlated with both
      acute and chronic histological changes. On histological examination the patients
      could be divided into three groups as follows: (1) all four biopsies were normal
      (group 1, n = 8, 14%), (2) the score of acute and chronic inflammation decreased
      from distal to proximal zones (group 2, n = 25, 42%) and (3) all four biopsies
      were abnormal with the same score (group 3, n = 26, 44%). The latter group
      significantly correlated with a present or past history of pouchitis. CONCLUSION:
      The study has shown that when there is a gradation of inflammation within the
      ileal reservoir this is more severe in distal than in proximal zones.

PMID- 9638498
TI  - Papillomavirus and anal carcinoma.
AB  - Human papilloma virus (HPV; 16 and 18) is known to play an important etiologic
      role in cervical dysplasia, but its relationship with anal carcinoma is still
      unclear. Surgical samples from 80 female patients treated for anal epidermoid
      carcinoma in the Polyclinic of Surgery in Geneva between 1976 and 1989 were
      retrospectively studied. Of these, HPV detection was performed in 41 whose DNA
      was preserved well enough to allow such an analysis. Seventeen (42%) samples
      contained HPV, with a high percentage of high risk HPV (15/41, 36%). Thirty-eight
      of the 80 patients had a cervical smear, of which 18% revealed cervical
      carcinoma. When compared with epidemiological data, the results of this study
      suggest that genital HPV infection predisposes not only to cervical cancer, but
      also to anal carcinoma, possibly by means of contiguous contamination.

PMID- 9638506
TI  - Telephone support for nurses in HIV/AIDS care.

PMID- 9638500
TI  - Time course of apoptosis in collagen-induced arthritis.
AB  - Recently, apoptotic cells were discovered in the synovial cells of rheumatoid
      arthritis patients. Their role, however, is unknown. We thus examined the time
      course of apoptosis in the synovium using an animal model of rheumatoid
      arthritis, in which arthritis was induced by intracutaneous injection of
      collagen. No apoptotic cells were detected before the onset of synovitis, but
      they increased in parallel with the progress of arthritis in its initial period,
      and decreased in the later chronic stages. Apoptotic cells appear to maintain the
      homeostasis of a joint when synovial proliferation occurs.

PMID- 9638505
TI  - Patients with HIV are safe to treat, says ANA.

PMID- 9638507
TI  - HIV-positive nurse wins precedent-setting case in Norway.

PMID- 9638503
TI  - Successful treatment of severe atopic dermatitis-complicated cataract and male
      infertility with a natural product antioxidant.
AB  - There has been a recent dramatic change in the features of atopic dermatitis and
      male infertility, including a marked increased prevalence of severe and treatment
      resistant atopic dermatitis; an increase in severe atopic dermatitis complicated
      by cataracts, especially in urban and industrial areas; and an increase in the
      number of infertile men with poor sperm motility. Previously we have attributed
      these changes to the increased free radicals produced by environmental toxicity.
      We have reported the increase in lipid peroxide levels and decrease in superoxide
      dismutase inducibility in severe atopic dermatitis patients, and shown that lipid
      peroxides attach to the stratum corneum, promoting loss of skin moisturization
      and resulting in the worsening of atopic dermatitis. Cataracts which occur with
      severe atopic dermatitis are also formed by the diffusing of lipid peroxides
      through the posterior lens. Regarding aspermia, the standard levels of sperm
      motility according to the World Health Organization Guidelines have been reduced
      to 50% from 60%, but nonetheless the prevalence of infertile men is increasing.
      It has been reported that antioxidants such as ascorbate, catalase and
      glutathione-Px can reverse the decrease in sperm motility in the seminal plasma
      of infertile men. We have developed an oral antioxidant, named AOA, which is
      produced from natural plants and seeds (e.g., soybean, sesame, wheat germ),
      treated by heating with far infrared rays (4-14 microns wavelength), brewed with
      Aspergillus oryzae, and lipophilized with similarly heated sesame oil. These
      procedures liberate low-molecular-weight antioxidants that exist naturally in an
      inactive form of repeating subunits of polymers, to produce free, activated forms
      of antioxidants. This natural medicinal product, AOA, has been applied to the
      treatment of both cataract complicated with atopic dermatitis and male
      infertility. Approximately half the patients tested have shown marked
      improvement.

PMID- 9638508
TI  - ICN promotes partnerships.
AB  - Partnership is today's keyword. As it has become evident that no one institution,
      group or individual can eliminate poverty, improve health status or solve any
      other societal problem alone, WHO, the World Bank and other UN agencies and
      nongovernmental organizations are on the search for partnerships, starting from
      the international down to the local level and involving all sectors, including
      private and public companies. An ICN core value, partnership is being promoted on
      International Nurses' Day, May 12, and throughout the year. In this issue,
      partnerships are called for in defending human rights (page 76), in curtailing
      the spread of HIV/AIDS (page 85) and in a community's health development (page
      81). Below, a review of how nurses can work hand in hand with their communities
      and others to improve health.

PMID- 9638501
TI  - Effects of a neutral endopeptidase inhibitor, BP102, on the development of
      deoxycorticosterone acetate-salt hypertension in kininogen-deficient Brown Norway
      Katholiek rats.
AB  - The nature of all of the peptides critical to the mechanism(s) of the
      antihypertensive action of neutral endopeptidase (NEP) inhibitors is still
      unclear, but bradykinin is thought to be one such peptide. This study was
      designed to assess the effectiveness of an NEP inhibitor in deoxycorticosterone
      acetate (DOCA)-salt treated kininogen-deficient Brown Norway Katholiek (BN-Ka)
      rats. Oral administration of BP102 (10-100 mg/kg), an NEP inhibitor, increased
      urine volume and urinary sodium excretion in a dose-dependent manner in
      anesthetized Sprague-Dawley rats. DOCA-salt hypertension was induced in both BN
      Ka and Brown Norway Kitasato (BN-Ki) rats after left nephrectomy. The development
      of DOCA-salt hypertension in normal BN-Ki rats was prevented, and that in BN-Ka
      rats was also significantly reduced, by an 8-day administration of BP102. When
      BP102 was administered for 5 weeks, the high blood pressure of DOCA-salt treated
      BN-Ka rats was markedly lowered, and their heart weights were reduced. These
      results suggest that kinins play no role in the antihypertensive effect of this
      inhibitor and that other factors may be involved in this effect.

PMID- 9638502
TI  - Long-term ethanol administration enhances urinary ultraweak luminescence and age
      dependent modulation of redox in central and peripheral organs of the rat.
AB  - Numerous experimental evidence sustains a pathogenic role for oxidative stress in
      aging. Acute and chronic ethanol metabolism is also known to be associated with
      oxidative perturbation of cellular oxidant/antioxidant balance. In the present
      work we investigated the effects of 25 months of ethanol consumption on the
      antioxidant defense system in different organs of rats, in comparison with normal
      and aged animals. We show that aged rats underwent a significant perturbation of
      the antioxidant defense system, as indicated by depletion of reduced glutathione
      content, increases in oxidized glutathione and free radical-induced urinary
      luminescence associated with a decrease of glutathione reductase and increase of
      glutathione transferase activities. These modifications, observed particularly in
      the liver and brain, were enhanced by long-term alcohol exposure. Our results
      indicate that increased glutathione transferase activity and decreased
      glutathione reductase activity, followed by thiol depletion, are important
      factors sustaining a pathogenic role for oxidative stress in aging and in all
      situations where age-correlated changes occur. They also reinforce the oxidative
      potential of toxic compounds, such as ethanol intoxication.

PMID- 9638499
TI  - Treatment of acute pain following removal of mandibular third molars. Use of the
      dental pain model in pharmacological research and development of a comparable
      animal model.

PMID- 9638509
TI  - Human Rights and torture.
AB  - 1998 marks the 50th anniversary of the historic Universal Declaration of Human
      Rights, which proclaims that all peoples are born free and equal and sets out the
      basic principles of equality and nondiscrimination in the enjoyment of
      fundamental freedoms and human rights. Yet, despite the many covenants and
      conventions stemming from this declaration and signed by nations around the
      world, human rights continue to be violated by powerful groups, by individuals,
      often even by family members. On 26 June, which has been declared UN
      International Day in Support of Victims of Torture, attention will be focused on
      torture--a grave violation of a person's human rights still practised in its many
      insidious forms in many countries. INR reviews the work of the organizations
      trying to help stop the perpetrators and participation of health professionals;
      rehabilitate the survivors; and educate health professionals and the public.

PMID- 9638510
TI  - Teaching health professionals about torture.

PMID- 9638504
TI  - Efficacy and tolerance of lysine clonixinate versus paracetamol/codeine following
      inguinal hernioplasty.
AB  - In this study lysine clonixinate, a nonsteroidal antiinflammatory agent with
      selective inhibition of cyclooxygenase-2 and 5-lipooxygenase in in vitro and in
      vivo pharmacodynamic studies, was evaluated in a prospective, randomized, double
      blind, double-dummy clinical study versus paracetamol/codeine, in 151 patients
      with pain following inguinal hernioplasty. Patients were treated with one 125 mg
      tablet of lysine clonixinate or paracetamol/codeine (500 mg + 30 mg) administered
      at fixed doses every 4 h during 2 days. Controls were carried out 1, 2 and 4 h
      after the first intake of day 1 and day 2. Each control included assessment of
      pain at rest, when coughing, sitting and upon moderate pressure. Both treatment
      groups (lysine clonixinate, 77 patients and paracetamol/codeine, 74 patients)
      were comparable in terms of demographic and baseline pain intensities.
      Spontaneous pain was reduced significantly in both treatment groups from the 1st
      h control. The following values were recorded in the lysine clonixinate group
      during day 1: baseline: 6.86 +/- 1.24; 1st h: 4.49 +/- 1.77; 2nd h: 2.96 +/-
      1.74; 4th h: 2.23 +/- 1.51. The following values for the same group during day 2
      were: predose: 1.70 +/- 1.64; 1st h: 1.16 +/- 1.17; 2nd h: 0.78 +/- 1.06; 4th h:
      0.63 +/- 1.05. The paracetamol/codeine group revealed the following values: day
      1: baseline: 6.72 +/- 1.22; 1st h: 4.57 +/- 1.72; 2nd h: 2.97 +/- 1.68; 4th h:
      2.47 +/- 1.68 and day 2: predose: 2.02 +/- 1.57; 1st h: 1.32 +/- 1.23; 2nd h:
      0.82 +/- 0.99; 4th h: 0.66 +/- 0.89. Reduction of pain induced by coughing,
      sitting and pressure showed similar behavior patterns. No significant differences
      between both treatment groups were encountered in terms of analgesic efficacy.
      Incidence of adverse effects was significantly higher in the paracetamol/codeine
      group (X2: p < 0.05): 11 out of 74 patients; three patients had to discontinue
      treatment. In the lysine clonixinate group four out of 77 patients showed side
      effects but these did not require treatment discontinuation.

PMID- 9638511
TI  - Empowering communities--a strategy used in Malawi.
AB  - In Malawi, community health nurses and environmental health officers are helping
      communities to solve their own health problems. Below, the lessons learned in one
      district.

PMID- 9638512
TI  - Nurses fighting the HIV/AIDS epidemic in Africa.
AB  - Nurses involved in HIV/AIDS care must contend with many practical, professional
      and ideological issues. In doing so they must also be activists for social
      justice and human rights in health care, especially in countries where poverty
      and lack of knowledge are inextricably linked to the spread of HIV. Below, a
      report on where nurses are and should be going in Africa.

PMID- 9638513
TI  - Nursing and health in Russia.
AB  - There are over one million nurses in Russia, and they work in a crippled
      healthcare system facing a dramatic increase in infectious diseases. But nurses
      are valiantly coping with the country's health crisis and becoming a recognized
      profession.

PMID- 9638514
TI  - Lipoproteins and cardiovascular risk-from genetics to CHD prevention.
AB  - Dyslipidemia is said to be present when lipid or lipoprotein levels lie within a
      range which is known from epidemiological studies to be associated with secondary
      complications, in particular atherosclerosis of the coronary arteries, or when a
      lipid or lipoprotein grossly deviates from the norm as in abetalipoproteinemia,
      hypobetalipoproteinemia or the HDL deficiency syndromes. In most cases,
      dyslipidemia is due not to a single genetic or environmental factor, but to a
      combination of the effects of several genes of small effect (polygenes) and
      environment. In other cases, however, dyslipidemia is caused by a mutation in a
      single gene of large effect. In such cases, the extent and nature of the
      phenotype depends primarily on the identity of the gene involved, but is also
      modulated to an important degree by the nature of the mutation and the genetic
      and environmental background against which this mutation occurs. In addition,
      many cases of hyperlipidemia are secondary to other disorders such as
      hypothyroidism or renal dysfunction. Such disorders may also unmask or exacerbate
      a genetic lipoprotein disorder. Examples of the latter are the unmasking of type
      III hyperlipidemia by diabetes mellitus or the exacerbation of familial
      hypercholesterolemia by hypothyroidism.

PMID- 9638515
TI  - Vascular dopamine-I receptors and atherosclerosis.
AB  - Vascular smooth muscle cell (VSMC) migration and proliferation are believed to
      play key roles in atherosclerosis. To elucidate the role of vascular dopamine D1
      like receptors in atherosclerosis, the effects of dopamine, specific D1-like
      agonists SKF 38,393, and YM 435 on platelet-derived growth factor (PDGF) BB
      mediated VSMC migration, proliferation, and hypertrophy were studied. We observed
      that cells stimulated by 5 ng/ml PDGF BB showed increased migration,
      proliferation and hypertrophy. These effects were prevented by coincubation with
      dopamine, SKF 38,393, or YM 435 at 1-10 mumol/l, and this prevention was reversed
      by Sch 23,390 (1-10 mumol/l), a specific D1-like antagonist. These actions are
      mimicked by 1-10 mumol/l forskolin, a direct activator of adenylate cyclase and 8
      bromocyclic AMP at 0.1-1 mmol/l. The actions are blocked by a specific protein
      kinase A (PKA) inhibitor N-[2-(p-bromocinnamylamino) ethyl]-5-isoquinoline
      sulfonamide (H 89), but are not blocked by its negative control, N-[2-(N-formyl-p
      chlorocinnamylamino) ethyl]-5-isoquinoline sulfonamide (H 85). PDGF-BB (5 ng/ml)
      mediated activation of phospholipase D (PLD), protein kinase C (PKC) and mitogen
      activated protein kinase (MAPK) activity were significantly suppressed by
      coincubation with dopamine. These results suggest that vascular D1-like receptor
      agonists inhibit migration, proliferation and hypertrophy of VSMC, possibly
      through PKA activation and suppression of activated PLD, PKC and MAPK activity.

PMID- 9638518
TI  - Effects of copper-zinc type superoxide dismutase on the proliferation and
      migration of cultured vascular smooth muscle cells induced by oxidized low
      density lipoprotein.
AB  - We have investigated the effects of copper-zinc type superoxide dismutase (Cu, Zn
      SOD) on the function of oxidized low density lipoprotein, utilizing cultured
      smooth muscle cells (SMC), obtained from rabbit aorta. We added native LDL
      (nLDL), minimally oxidized LDL (MmLDL) and copper ion-induced oxidized LDL
      (OxLDL) to the culture media. No remarkable change was found out by adding nLDL.
      The numbers of SMC, including migrated SMC, were increased by the addition of
      MmLDL. Cu, Zn-SOD significantly inhibited the reactions induced by MmLDL. The SMC
      numbers were markedly decreased by OxLDL addition without recovery by adding Cu,
      Zn-SOD. Thus, MmLDL significantly promoted the SMC proliferation and migration.
      OxLDL revealed strong cytotoxicity against SMC. Cu, Zn-SOD inhibited both the
      migration and the proliferation of SMC induced by MmLDL, and did not alter the
      effect of OxLDL. In conclusion, Cu, Zn-SOD inhibited some functions of MmLDL, and
      may play an important role in protecting against the atherosclerotic processes
      evoked by MmLDL.

PMID- 9638516
TI  - Molecular mechanisms of the exaggerated growth of vascular smooth muscle cells in
      hypertension.
AB  - The molecular mechanisms of the exaggerated growth of vascular smooth muscle
      cells (VSMC) in hypertension are reviewed based on our previous experimental
      data. Spontaneously hypertensive rats (SHR)-derived VSMC increasingly express
      angiotensinogen, cathepsin D and angiotensin-converting enzyme (ACE) mRNAs,
      compared to cells from normotensive Wistar-Kyoto (WKY) rats, indicating the
      presence of an Ang II generating system in a homogeneous culture of VSMC from
      SHR. The produced Ang II then induces TGF-beta. SHR-derived VSMC show the
      distinct expression and abnormal regulation by Ang II of TGF-beta receptors when
      compared with cells from WKY rats, which express TGF-beta type II receptor
      predominantly to induce PDGF A-chain stimulation of VSMC growth. These findings
      imply that the increased growth of VSMC in hypertension is a primary event
      independent of high blood pressure, and is associated with endogenous Ang II
      related growth factors.

PMID- 9638517
TI  - Cytotoxicity of some oxysterols on human vascular smooth muscle cells was
      mediated by apoptosis.
AB  - A decrease in smooth muscle cells is observed in advanced atherosclerotic lesion.
      To understand this mechanism, we selected oxysterols as candidates for toxic
      lipid, and examined their cytotoxicity on human cultured vascular smooth muscle
      cells, together with the manner of cell death. In the presence of 7
      ketocholesterol or 7 beta-hydroxycholesterol (50 mumol/L), the percentage of
      detached cells increased significantly with dose dependency, and an increase in
      detached cell number and DNA nick detected by terminal deoxynucleotidyl
      transferase-mediated dUTP-biotin nick end labeling study (TUNEL) preceded an
      increase in lactate dehydrogenase released into the medium. DNA extracted from
      smooth muscle cells incubated with 7-ketocholesterol or 7 beta-hydroxycholesterol
      showed a laddering pattern on agarose electrophoresis. In the presence of 7
      ketocholesterol or 7 beta-hydroxycholesterol, fragmented DNA quantified by the
      quantitative sandwich enzyme immunoassay was significantly increased. From these
      results, it is proposed that 7-ketocholesterol and 7 beta-hydroxycholesterol are
      toxic to smooth muscle cells, and that this cytotoxicity is mediated by
      apoptosis.

PMID- 9638519
TI  - Effects of pressor substances on low density lipoprotein peroxidation by Cu++.
AB  - To investigate whether pressor substances accelerate low density lipoprotein
      peroxidation by Cu++, low density lipoprotein was dialysed against physiological
      saline containing O-5 mumol/l CuCl2 and/or 1 mumol/l of various pressor
      substances. Lipid peroxide value of low density lipoprotein changed little with
      the addition of norepinephrine to the saline, but the addition of norepinephrine
      to 1 mumol/l CuCl2 accelerated the peroxidation. When low density lipoprotein was
      dialysed against saline with norepinephrine, epinephrine, serotonin or dopamine,
      there were no significant differences in the lipid peroxide values of low density
      lipoprotein. Although the addition of serotonin into the dialyzate did not
      accelerate the peroxidation of low density lipoprotein due to Cu++, the addition
      of norepinephrine, epinephrine and dopamine accelerated the Cu(++)-peroxidation
      with a significant increase in the acceleration rate starting at the 36 hour
      point. Thus, it is speculated that various stresses stimulating the sympathetic
      nervous system accelerate the peroxidation of low density lipoprotein and produce
      peroxidized low density lipoprotein in the blood.

PMID- 9638520
TI  - Elevation of plasma lipid peroxides in non-insulin dependent diabetics with
      multiple lacunar infarcts.
AB  - Our purpose was to determine whether lipid peroxides are elevated in the plasma
      of patients with non-insulin dependent diabetes with multiple lacunar infarcts as
      detected by magnetic resonance imaging (MRI), and to confirm whether peroxide
      levels correlate with glycemic controls and blood lipid levels. The level of
      lipid peroxide (measured as thiobarbituric acid reactive substances (TBARS)) was
      measured in 23 healthy controls and 28 diabetics showing normal MRI findings and
      22 diabetics with multiple lacunar infarcts. These groups were age-matched. In
      patients with multiple lacunar infarcts, systolic blood pressure, diastolic blood
      pressure and TBARS levels were significantly higher than in diabetics without
      such infarcts (p < 0.05). When the diabetic patients were divided into two groups
      according to the presence or absence of hypertriglyceridemia or hyperglycemia, in
      both groups plasma TBARS levels in patients with multiple lacunar infarcts were
      significantly higher than in patients without such infarcts. Multivariate
      analysis showed systolic blood pressure and plasma TBARS levels to be independent
      predictors of multiple lacunar infarcts. Among diabetics, total plasma TBARS
      levels were positively correlated with fasting blood glucose, HbA1c and
      triglyceride levels, but not with total cholesterol levels and age. In conclusion
      plasma lipid peroxides were elevated in diabetics with multiple lacunar lesions,
      and are related to the metabolic imbalance of plasma glucose and lipids.

PMID- 9638523
TI  - Biocompatibility of poly(etherurethane urea) containing dehydroepiandrosterone.
AB  - Poly(etherurethane urea) (PEUU) elastomers, with their broad range of mechanical
      properties and high biocompatibility, are used clinically for medical
      applications. However, the possibility exists for the ether soft segment of PEUU
      to degrade in long-term uses. To retard degradation, antioxidants that scavenge
      reactive oxygen intermediates are added. In this study, we incorporated
      dehydroepiandrosterone (DHEA), which functions by the alternate mechanism of
      modulating or down-regulating adherent macrophage activity, to retard the
      biodegradation of PEUUs. Biocompatibility of PEUU samples containing 1% DHEA, 5%
      DHEA, and 5% vitamin E (alpha-tocopherol) by weight were studied in vivo and in
      vitro. The biocompatibility was initially evaluated by examination of the
      inflammatory cellular exudate. Compared to PEUU without additives and PEUU with
      5% vitamin E, the addition of 5% DHEA to PEUU caused a decrease in the total
      leukocyte exudate concentration at 4 days. The addition of 5% DHEA also caused
      lower macrophage adhesion and FBGC formation compared to the other materials at 7
      days. Despite these short-term effects, the biocompatibility at later time points
      (14, 21, and 70 days) was similar for all materials. Transmission infrared
      analysis of the materials revealed that more than 70% of the DHEA had leached out
      of the samples by 3 days implantation. Furthermore, through attenuated total
      reflectance Fourier transform analysis and scanning electron microscopy, it was
      determined that unlike vitamin E, DHEA did not enhance long-term PEUU
      biostability. The effect of DHEA on inflammatory cell activity appeared to be
      dose dependent, with improved biocompatibility in vivo for higher loading levels
      of DHEA, but the overall effect was limited owing to the rapid diffusion of the
      water-soluble DHEA from the PEUU.

PMID- 9638525
TI  - Effects of hyaluronan viscous materials on cell membrane electrical properties.
AB  - Hyaluronan [hyaluronic acid (HA)] has been implicated in various cellular
      processes such as proliferation, adhesion, migration, and differentiation. The
      secondary and tertiary structures of HA give it very important and unique
      viscoelastic properties. HA-composed materials are currently used intraocularly
      during ophthalmological surgery to facilitate surgical procedures and prevent
      tissue damage. To examine the effects of three viscous biomaterials composed of
      hyaluronan (Healon, IAL, and Biolon) used in ophthalmological surgery, the
      membrane electrical properties of the erythroleukemic K562 cell line exposed to
      these materials were investigated. Membrane conductivity, membrane permittivity,
      and the conductivity of the cytosol were evaluated using dielectric relaxation
      measurements in the radiofrequency range and fitting the experimental results to
      the general equations of the Maxwell-Wagner effect. The results demonstrate that
      while membrane permittivity and the conductivity of the cytosol are not
      significantly altered, the membrane conductivity of K562 cells exposed to all
      three biomaterials increases substantially and in a time-dependent manner with
      respect to untreated cells. These observations seem to indicate that hyaluronan
      perturbs ionic transport while it does not vary the type, quantity, or
      distribution of membrane components. In addition, the variations induced by these
      substances on the cell membrane are not dependent upon the molecular weight or on
      the biological origin of hyaluronan. These results may aid in elucidating the
      mechanisms involved in hyaluronan/cell membrane interaction and thus may provide
      a deeper understanding of the complications related to their use in
      ophthalmological surgery.

PMID- 9638521
TI  - Human monocyte/macrophage adhesion, macrophage motility, and IL-4-induced foreign
      body giant cell formation on silane-modified surfaces in vitro. Student Research
      Award in the Master's Degree Candidate Category, 24th Annual Meeting of the
      Society for Biomaterials, San Diego, CA, April 22-26, 1998.
AB  - A cytokine-based, in vitro model of foreign body giant cell (FBGC) formation was
      utilized to examine the effect of biomaterial surface chemistry on the adhesion,
      motility, and fusion of monocytes and macrophages. Human monocytes were cultured
      for 10 days on 14 different silane-modified glass surfaces, during which time the
      cells assumed the macrophage phenotype. The adhesion of monocytes and macrophages
      during the culture period decreased by an average of approximately 50%, with the
      majority of cell loss observed during days 1-3. Most important, the adhesion of
      monocytes and macrophages was surface independent except for two surfaces
      containing terminal methyl groups, which decreased adhesion levels. Interleukin-4
      (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were added
      to the medium to induce FBGC formation and enhance macrophage adhesion,
      respectively. Surprisingly, GM-CSF decreased long-term monocyte/macrophage
      adhesion. IL-4-induced FBGC density was strongly influenced by the surface carbon
      content, as determined by X-ray photoelectron spectroscopy (XPS). In contrast,
      contact angle and surface energy displayed no correlation with FBGC formation.
      The motility of adherent macrophages, as measured by time-lapse confocal
      microscopy, was not affected significantly by differences in surface chemistry or
      the addition of cytokines. The surface dependence of FBGC formation is
      hypothesized to be the result of varying levels of silane-derived surface carbon.

PMID- 9638524
TI  - Inhibition of the tissue reaction to a biodegradable biomaterial by monoclonal
      antibodies to IFN-gamma.
AB  - Biomaterials are increasingly used for clinical applications. However, loss of
      function may occur owing to tissue reactions, which are mainly caused by a
      variety of inflammatory reactions. Recently, we demonstrated that macrophages
      (MO) and T cells play key roles in these reactions. Since immunological studies
      showed that the T cell-derived cytokine interferon-gamma (IFN-gamma) activates
      MO, the aim of this study was to investigate the possibility of modulating tissue
      reactions to biodegradable biomaterials by inactivating IFN-gamma. Dermal sheep
      collagen (DSC) was used as a test biomaterial. DSC impregnated with anti-IFN
      gamma or phosphate-buffered saline (control) was implanted in rats. The results
      showed that cellular ingrowth and formation and function of giant cells were
      strongly delayed by anti-IFN-gamma. Also, MHC class II expression was strongly
      inhibited. In the treated DSC, some huge giant cells were formed at the interface
      but association with the DSC bundles did not occur. Finally, in both the control
      and treated DSC, T cells and NK cells were rarely detected. This study
      demonstrates that IFN-gamma plays an important role in the inflammatory reaction
      to biomaterials. This reaction can be modulated by anti-IFN-gamma, which warrants
      further studies of anti-IFN-gamma for clinical application to prevent unwanted
      tissue reactions to biomaterials.

PMID- 9638527
TI  - Preparation of calcium phosphate coatings on titanium implant materials by simple
      chemistry.
AB  - A two-step chemical treatment has been developed in our group to prepare
      commercially pure titanium (cpTi) surfaces that will allow calcium phosphate (Ca
      P) precipitation during immersion in a supersaturated calcification solution
      (SCS) with ion concentrations of [Ca2+] = 3.10 mM and [HPO4(2-)] = 1.86 mM. It
      was observed that a precalcification (Pre-Ca) procedure prior to immersion could
      significantly accelerate the Ca-P deposition process. In this work, the
      bioactivity of chemically treated cpTi and Ti6Al4V was further verified by
      applying commercially available Hanks' balanced salt solution (HBSS), an SCS with
      very low ion concentrations of [Ca2+] = 1.26 mM and [HPO4(2-)] = 0.779 mM, as the
      immersion solution. It was found that a uniform and very dense apatite coating
      magnesium impurities was formed if the Pre-Ca procedure was performed before
      immersion, as compared with the loose Ca-P layer obtained from the abovementioned
      high concentration of SCS. The formation of a microporous titanium dioxide thin
      surface layer on cpTi or Ti6Al4V by the two-step chemical treatment could be the
      main reason for the induction of apatite nucleation and growth from HBSS.
      Variations of pH values, Ca and P concentrations, and immersion time in HBSS were
      investigated to reveal the detailed process of Ca-P deposition. The described
      treatments provide a simple chemical method to prepare Ca-P coatings on both cpTi
      and Ti6Al4V.

PMID- 9638528
TI  - Application of solubility parameter theory to dentin-bonding systems and adhesive
      strength correlations.
AB  - The principal aim of this study was to investigate the relationships between the
      solubility parameters of ectched dentin, and adhesive primer solutions and
      adhesive bond strength. Solubility parameters characterize the molecular
      interactions which determine physical properties such as wetting, and thus can
      serve as tools to aid development of polymeric adhesives and interpenetrating
      polymer networks. If an adhesive monomer has a solubility parameter close to that
      of a polymer substrate, then the monomer may act as a solvent for the polymer and
      penetrate below the surface. Subsequent polymerization of the monomer may then
      produce an interpenetrating network, thus adhering without necessarily forming
      primary chemical bonds to the substrate. The dentin substrate considered in this
      study was abraded dentin treated with ethylenediaminetetraaceitc acid. Solubility
      parameters delta pr, delta h, and delta d calculated for the etched dentin
      substrate were 20.3, 23.6, and 16.0 (J/cm3)1/2, respectively. Solubility
      parameters of the primers were expressed using Hansen's three-dimensional scheme.
      The data indicate a correlation between the calculated solubility parameters of
      the etched dentin, and dentin primers and the resulting bond strengths. The
      results corroborate the significance of solubility parameter considerations for
      adhesive bonding to dentin.

PMID- 9638526
TI  - Thermal analysis of bones from ovariectomized rats.
AB  - Thermal analyses [thermogravimetry (TG) and differential thermal analysis (DTA)],
      X-ray diffraction, and infrared absorption analysis of bones from ovariectomized
      rats were carried out. The rats were divided into five groups: sham operated
      (Sham); ovariectomized (OVX); OVX given traditional Chinese (Kampo) medicine,
      Unkei-to; OVX given 17 beta-estradiol; and OVX given the estradiol vehicle,
      respectively. The activation energy (delta E), a kinetic parameter from TG data
      of OVX rats, increased by 57% from that in Sham rats. The administration of Unkei
      to and 17 beta-estradiol to OVX rats clearly restored the delta E to the levels
      of Sham rats, while the vehicle for 17 beta-estradiol had no effect. DTA data
      from thermal analyses of rats from the Sham, OVX, and OVX given various compounds
      were almost the same except for OVX rats given 17 beta-estradiol. The X-ray
      diffraction pattern and infrared absorption spectrum of bone powders from Sham
      rats were not different from those of OVX rats or others. These results strongly
      suggest that kinetic parameter, delta E calculated from TG data, may be a useful
      method for assessing both experimentally induced osteoporosis and drug effects on
      it.

PMID- 9638530
TI  - Creating molecular barriers to acute platelet deposition on damaged arteries with
      reactive polyethylene glycol.
AB  - We report here a novel method for blocking acute platelet deposition at the site
      of vessel injury by molecularly masking thrombogenic vascular wall proteins with
      covalently attached polyethylene glycol (PEG). To evaluate this technique, blood
      containing 111In-labeled platelets was perfused over damaged human placental
      arteries for 2 min at a wall shear rate of 200 s-1. Denuded vessel segments were
      incubated for 30, 15, 5, and 1 min with a solution of either reactive PEG
      diisocyanate (PEG-ISO) or nonreactive PEG-dihydroxyl (PEG-OH). Vessels treated
      with PEG-ISO for 1 min exhibited 87 +/- 12% less platelet deposition (p < 0.01)
      than untreated control vessels, and this reduction did not vary significantly
      among treatment times, indicating that this reaction occurs rapidly enough to be
      clinically applicable. To investigate the duration of this thrombotic barrier,
      denuded pig carotid arteries were treated with reactive PEG-ISO for 1 min,
      perfused with plasma for 30 min, and then perfused with blood containing
      radiolabeled platelets. PEG-ISO-treated arteries exhibited 84 +/- 9% less
      platelet deposition (p < 0.05) than untreated controls. These data demonstrate
      that damaged arterial surfaces can be rendered resistant to platelet deposition
      after short contact periods with reactive PEG. Molecular PEG barriers ultimately
      might find application following vascular procedures to sterically inhibit blood
      cell interaction with damaged vascular surfaces.

PMID- 9638529
TI  - Development of a novel osteochondral graft for cartilage repair.
AB  - This study reports the development of a novel osteochondral graft for cartilage
      repair. A technique of proteoglycan extraction via timed enzymatic digestion with
      hyaluronidase and trypsin and subsequent processing with a chloroform-methanol
      solution to remove cellular debris from a fresh-frozen bovine osteochondral
      sample is a method described to prepare a stable biological carrier of low
      immunogenicity. Lyophilization of the carrier followed by rehydration in a
      suspension of lapine chondrocytes produced a chimeric xenograft that succeeded in
      vivo in enhancing cartilage repair. In a pilot study, full-thickness articular
      cartilage defects treated with these xenografts demonstrated improved healing
      compared to untreated defects or defects treated with unseeded grafts at 2, 6,
      and 12 weeks postimplantation. The xenograft provoked a mild inflammatory
      response; however this did not impede the repair process. Further investigation
      of this novel chimeric xenograft eventually may yield a method of cartilage
      repair superior to current methods of treatment.

PMID- 9638531
TI  - Effects of polyelectrolyte complex (PEC) on human periodontal ligament fibroblast
      (HPLF) function. I. Three-dimensional structure of HPLF cultured on PEC.
AB  - Human periodontal ligament fibroblast (HPLF) cultured on tissue culture dishes
      (TCD), irrespective of the presence of serum, showed only a spreading form. In
      contrast, using polyelectrolyte complex (PEC) as a matrix, HPLF showed spreading,
      round, and aggregate forms. Cells of the inner part of the aggregate contacted
      with each other to form a three-dimensional structure, and this condition
      corresponded to typical tissues in vivo. These seemed to be related to the
      interrelation between growth and morphology; that is, the HPLF of the spreading
      form was considered to belong to a proliferation phase, and the HPLF of the round
      and aggregate forms, with a little growth, seemed to belong to a functional phase
      of the cell cycle, indicating that PEC is able to control such cell functions as
      proliferation, morphology, and differentiation. The cell aggregate was observed
      only on PEC with carboxymethyl residues and was stained by alizarin red (AR),
      which suggested mineralization. The spreading cells on PEC containing sulfate
      residues were not stained by AR. Therefore, it was found that there was a certain
      relationship between cell growth and morphology, and that PEC affected the cell
      cycle and promoted proliferation and differentiation of HPLF.

PMID- 9638522
TI  - In vitro formation by reverse dialysis of collagen gels containing highly
      oriented arrays of fibrils.
AB  - Acid extracts of rat tail tendon were subjected to reverse dialysis against 0.5%
      PEG at 4 degrees C in an attempt to induce liquid crystallization. After 48 h,
      gel and fibril formation were initiated by continuing dialysis at 20 degrees C
      against the same PEG solution adjusted to pH 7.4. The inclusion of calcium- or
      magnesium chloride (final concentration 0.3-33 mM) in the collagen solution
      before dialysis resulted in strongly birefringent gels that showed a progressive
      rotation of the slow axis of birefringence with increasing distance from the
      lateral margin of the gel. The gels contained fibers running predominantly in the
      plane of the flattened gel and crossing at angles of between 55 degrees and 90
      degrees. We suggest that liquid crystallization is responsible for this
      phenomenon and that it might be possible to exploit this to produce materials for
      tissue engineering.

PMID- 9638534
TI  - X-ray diffraction and polarizing optical microscopy investigation of the
      structural organization of rabbit tibia.
AB  - X-ray diffraction and polarized optical microscopy investigations were carried
      out on thin sections of rabbit tibia in order to study the morphological
      organization of the structural components of this tissue, which often is utilized
      to test bone response to implants. In the optical microscope, the lateral face as
      well as the lateral portion of the caudal face exhibit a lamellar structure with
      an alternation of dark and bright lamellae running parallel to the long axis of
      the tibia. In contrast, both in the medial face and in the medial portion of the
      caudal face there are numerous osteonic structures. In spite of the complexity of
      this morphological organization, the results of small- and high-angle X-ray
      diffraction analyses indicate that the structural relationship between collagen
      fibrils and inorganic crystals is quite similar to that observed in single
      osteons and allows evaluation of the orientation of the two main structural
      components. Both collagen fibrils and apatitic crystallites are preferentially
      oriented parallel to the long axis of the tibia. The degree of orientation is
      greater in the thickness than in the plane of the lamellae, suggesting that
      collagen fibrils and inorganic crystallites lie preferentially in the plane of
      the lamellae, where they follow an oblique course. The degree of orientation of
      the apatitic crystallites is higher in the lateral face than in the medial and
      caudal faces, in agreement with the optical microscopic images. The results
      provide information that must be taken into account when evaluating the
      structural modifications of bone due to the insertion of a prosthetic device.

PMID- 9638532
TI  - Effects of polyelectrolyte complex (PEC) on human periodontal ligament fibroblast
      (HPLF) function. II. Enhancement of HPLF differentiation and aggregation on PEC
      by L-ascorbic acid and dexamethasone.
AB  - In addition to many types of extra cellular matrix (ECM) in vivo, cells are
      stimulated by many types of vitamins, hormones, growth factors, etc. In this
      paper the effects of L-ascorbic acid 2-phosphate (Asc-2P) and dexamethasone (Dex)
      on proliferation and differentiation of human periodontal ligament fibroblast
      (HPLF) using polyelectrolyte complex (PEC) as a matrix in vitro will be
      discussed. The PEC was composed of chitosan as a polycation, with carboxymethyl
      (CPEC) or sulfated chitin (SPEC). Asc-2P (0.2 mM) inhibited the growth of HPLF on
      CPEC, but promoted the growth on SPEC. Moreover, the aggregation of HPLF on CPEC
      was inhibited by Asc-2P, but that on SPEC was induced in the presence of Asc-2P
      and Dex. Although Asc-2P reduced an increase in alkaline phosphatase (ALPase)
      activity of HPLF on CPEC as well, it induced a twofold increase in ALPase
      activities on SPEC and TCD. Furthermore, in the medium containing Asc-2P and 100
      mM of Dex, cell growth was inhibited, but ALPase activity was promoted on both
      SPEC and TCD to form many aggregates on SPEC. ALPase activity increased by
      twofold over that of HPLF cultured in the medium containing only Asc-2P.
      Therefore, it is suggested that the cell functions of HPLF are controlled by the
      combination of PEC and additives.

PMID- 9638533
TI  - Modification of glassy carbon surfaces with synthetic laminin-derived peptides
      for nerve cell attachment and neurite growth.
AB  - Interactions between cultured nerve cells and surfaces are of importance for the
      implantation of biocompatible electrode materials such as glassy carbon (GC).
      Since implants serve as recording sensors in prosthetic neuroscience, we
      investigated whether coating electrodes with certain laminin derivatives
      containing the peptide sequences SIKVAV, CDPGYIGSR, PDSGR, YFQRYLI, and
      RNIAEIIKDA influences neuronal adhesion and neurite outgrowth in vitro. The
      coating of GC was performed by electrochemical polymerization and, for
      comparison, by adsorption or covalent coupling. Electrochemical polymerization is
      suitable for the coupling of peptides to GC, as shown by amino acid analysis and
      sequencing. Embryonic chicken retinal ganglion cells and brain cells (days E7 or
      E17) were used for both attachment and growth studies. Surfaces made by
      electrochemical polymerization of peptides were more efficient than those made by
      adsorption or covalent coupling of peptides. Synthetic cyclic peptide derivatives
      of CDPGYIGSR and 18-mer SIKVAV were found to be more efficient than the linear
      peptides. Competitive effects that resulted in a decreased cell attachment could
      be found upon application of soluble peptides. Nevertheless, irrespective of the
      method of coating, peptides were less efficient compared with the whole laminin
      molecule, as expected from its multiple adhesion sites. When small GC pins were
      implanted into the brain of E17 chicken after coating with the 18-mer SIKVAV
      peptide, nerve cell attachment was observed in vivo. The results suggest that
      chronically implantable materials may exert a higher neurocompatibility when
      coated with synthetic peptides.

PMID- 9638536
TI  - Platelet adhesion onto wettability gradient surfaces in the absence and presence
      of plasma proteins.
AB  - A wettability gradient was prepared on lowdensity polyethylene (PE) sheets by
      treating them in air with a corona from a knife-type electrode the power of which
      increased gradually along the sample length. The PE surfaces oxidized gradually
      with the increasing corona power and a wettability gradient was created on the
      surfaces, as evidenced by the measurement of water contact angles, Fourier
      transform infrared spectroscopy in the attenuated total reflectance mode, and
      electron spectroscopy for chemical analysis. The wettability gradient surfaces
      prepared were used to investigate the adhesion behavior of platelets in the
      absence and presence of plasma proteins in terms of the surface
      hydrophilicity/hydrophobicity of polymeric materials. The platelets adhered to
      the wettability gradient surfaces along the sample length were counted and
      examined by scanning electron microscopy (SEM). It was observed that the platelet
      adhesion in the absence of plasma proteins increased gradually as the surface
      wettability increased along the sample length. The platelets adhered to the
      hydrophilic positions of the gradient surface also were more activated (possessed
      more pseudo pods as examined by SEM) than on the more hydrophobic ones. However,
      platelet adhesion in the presence of plasma proteins decreased gradually with the
      increasing surface wettability; the platelets adhered to the surface also were
      more activated on the hydrophobic positions of the gradient surface. This result
      is closely related to plasma protein adsorption on the surface. Plasma protein
      adsorption on the wettability gradient surface increased with the increasing
      surface wettability. More plasma protein adsorption on the hydrophilic positions
      of the gradient surface caused less platelet adhesion, probably due to platelet
      adhesion inhibiting proteins, such as high-molecular-weight kininogen, which
      preferably adsorbs onto the surface by the so-called Vroman effect. It seems that
      both the presence of plasma proteins and surface wettability play important roles
      for platelet adhesion and activation.

PMID- 9638538
TI  - Engineering smooth muscle tissue with a predefined structure.
AB  - Nonwoven meshes of polyglycolic acid (PGA) fibers are attractive synthetic
      extracellular matrices (ECMs) for tissue engineering and have been used to
      engineer many types of tissues. However, these synthetic ECMs lack structural
      stability and often cannot maintain their original structure during tissue
      development. This makes it difficult to design an engineered tissue with a
      predefined configuration and dimensions. In this study, we investigated the
      ability of PGA fiber-based matrices bonded at their fiber crosspoints with a
      secondary polymer, poly-L-lactic acid (PLLA), to resist cellular contractile
      forces and maintain their predefined structure during the process of smooth
      muscle (SM) tissue development in vitro. Physically bonded PGA matrices exhibited
      a 10- to 35-fold increase in the compressive modulus over unbonded PGA matrices,
      depending on the mass of PLLA utilized to bond the PGA matrices. In addition, the
      bonded PGA matrices degraded much more slowly than the unbonded matrices. The
      PLLA bonding of PGA matrices had no effect on the ability of cells to adhere to
      the matrices. After 7 weeks in culture, the bonded matrices maintained 101 +/- 4%
      of their initial volume and an approximate original shape while the unbonded
      matrices contracted to 5 +/- 1% of their initial volume with an extreme change in
      their shape. At this time the bonded PGA matrices had a high cellularity, with
      smooth muscle cells (SMCs) and ECM proteins produced by these cells (e.g.,
      elastin) filling the pores between PGA fibers. This study demonstrated that
      physically bonded PGA fiber-based matrices allow the maintenance of the
      configuration and dimensions of the original matrices and the development of a
      new tissue in a predefined three-dimensional structure. This approach may be
      useful for engineering a variety of tissues of various structures and shapes, and
      our study demonstrates the importance of matching both the initial mechanical
      properties and the degradation rate of a matrix to the specific tissue one is
      engineering.

PMID- 9638541
TI  - Cost of diabetes-related amputations in minorities.
AB  - The objective of this study was to identify the direct cost and length of
      hospitalization of diabetes-related lower extremity amputations among Hispanics,
      African Americans, non-Hispanic whites, and Asians. The authors used a database
      from the office of Statewide Planning and Development in California that
      identified all hospitalizations for lower extremity amputations in the state in
      1991. Amputation level was defined by the ICD-9-CM codes 84.11-84.18. The total
      hospital charges for diabetes-related lower extremity amputations for the state
      of California in 1991 was $141 million. The mean hospital charge (HC) per patient
      with all ethnic groups combined was $27,930; and the mean length of stay (LOS)
      was 15.9 days. African Americans had significantly higher mean charges ($32,383)
      and longer stays (17.3 days) compared to all other ethnic groups (p < .05). Toe
      level amputations had lower HC (p < .05) and LOS (p < .01) than other amputation
      levels for all race groups. One-quarter of the population received multiple
      amputations during their hospital stay. These patients incurred significantly
      higher hospital charges ($44,731) and stayed in the hospital longer (23.4 days)
      than those receiving only a single amputation. There was a considerable variation
      in the HC and LOS among ethnic groups by level of amputation. The direct charges
      reported in this study suggest considerably higher overall direct costs than have
      been previously reported in the medical literature. The greater burden of disease
      experienced by African Americans is probably related to their higher amputation
      cost and longer hospitalization.

PMID- 9638540
TI  - Functional outcome in the elderly following lower extremity amputation.
AB  - Data regarding functional outcome in the elderly following major lower extremity
      amputation (LEA) are minimal. In the general diabetic population there is a
      significant mortality associated with these procedures, with the 5-year survival
      rates approaching only 40%. Contrasts between this group and the nondiabetic
      population will help to clarify the morbidity of these procedures and
      substantiate efforts at limb salvage. The authors review their experience with
      patients 80 years of age and above undergoing major LEA between 1990 and 1995
      with a specific focus on postoperative mortality and functional status. Forty-one
      patients were studied, 67% of whom had diabetes mellitus. Postoperative
      functional status remained unchanged in 40% and worsened in 55% of patients,
      while residential status was unchanged in 68% and worsened in 32%. The median
      survival for patients with and without diabetes was 19 and 49 months,
      respectively. The 5-year survival for the entire group was 25% and was not
      statistically different in the two subgroups. The authors conclude that major LEA
      in the very elderly is associated with a considerable mortality and deterioration
      of functional and residential status.

PMID- 9638539
TI  - Complement activation and inflammation triggered by model biomaterial surfaces.
AB  - Biomaterial-mediated complement activation repeatedly has been invoked as a
      trigger of phagocyte reactions and inflammation. However, a direct correlation
      between complement activation and inflammatory responses to biomaterial surfaces
      has yet to be established. Using an animal implantation model and gold surfaces
      bearing various thiol-linked functionalities, we investigated the potency of
      different surface groups in prompting complement activation in vitro and surface
      mediated accumulation of inflammatory cells in vivo. Among the surfaces tested,
      mercaptoglycerol- and mercaptoethanol-bearing surfaces engendered the strongest
      inflammatory responses, as reflected by the accumulation of large numbers of
      adherent neutrophils and monocytes/macrophages. In contrast, L-cysteine-coated
      surfaces caused only minor inflammatory responses, and both glutathione-modified
      and untreated gold implants attracted minimal numbers of inflammatory cells. The
      accumulation of inflammatory cells on mercaptoglycerol surfaces appears to arise
      from surface-mediated complement activation because complement-depleted animals
      failed to exhibit inflammatory responses to mercaptoglycerol-modified implants.
      Furthermore, there is a close relationship between surface-mediated complement
      activation (as measured by in vitro iC3b/C5b-9 generation and C3 deposition) and
      in vivo inflammatory responses. At least in this animal model and with these
      model surfaces, our results indicate that surface-mediated complement activation
      can be responsible for the subsequent accumulation of inflammatory cells on
      implant surfaces.

PMID- 9638535
TI  - Differences in microstructural characteristics of dense HA and HA coating.
AB  - Two implant types of hydroxyapatite (HA) currently are available for dental
      implants: dense HA-cemented titanium (Ti) and HA-coated. It has been shown in
      previous reports that there are differences in the chemical and mechanical
      stabilities between the dense HA and HA coated. The differences are thought to be
      due to structural differences between the two ceramic types. The aim of this
      study was to investigate the differences in microstructural characteristics of
      currently available dense HA and HA coated implants before implantation and at
      periods of 3 weeks and 10 months after implantation in canine bone. X-ray
      diffractometry, infrared analysis, transmission electron microscopy, and energy
      dispersive X-ray analysis were used. The dense HA is composed of crystal grains,
      with a well crystallized structure of HA, closely bound to each other and
      approximately 0.4-0.6 micron in size. Implantation did not change the original
      sintered structure of the dense HA. The HA coating was composed of an amorphous
      phase with a Ca/P ratio of 1.46 and a crystal phase consisting of
      oxyhydroxyapatite, tricalcium phosphate, tetracalcium phosphate, and CaO, with a
      Ca/P ratio of 1.57. In the amorphous phase, compared to other portions in the
      amorphous phase, there were some layers with lower atomic density and with no
      significant difference in Ca/P ratio. After implantation, the crystallization of
      super fine crystals of approximately 4-5 nm in thickness occurred in the
      amorphous phase, and with time it progressed and spread from the surface to the
      deeper portion of the HA coating. A Ca/P ratio of 1.58 in the crystallized
      portion was close to the ratio (1.60) in the dense HA, suggesting that the super
      fine crystals were HA. This crystallization cannot significantly decrease the
      solubility of the amorphous phase portion and poses risks of stress accumulation
      within the coating and a decrease of binding strength between the HA coating and
      the substrate.

PMID- 9638542
TI  - Beneficial effects of electrical stimulation on neuropathic symptoms in diabetes
      patients.
AB  - Transcutaneous electrical nerve stimulation is utilized for relieving pain in the
      diabetes peripheral neuropathy. Previous studies were short-term and did not
      document sustained beneficial effects. In this study, the authors evaluated long
      term effectiveness of electrotherapy administered by proprietary equipment, an H
      wave machine. A detailed questionnaire concerning patients' symptoms prior to and
      following electrotherapy was mailed to the users of H-wave machine. The responses
      of 34 individuals who had diabetes mellitus were analyzed (age 74.1 +/- 1.6 SEM
      years, body mass index 28.5 +/- 0.8 kg/m2, duration of diabetes 15.8 +/- 2.0
      years and duration of neuropathic symptoms 8.0 +/- 1.8 years). Telephone
      interviews were conducted with 20 additional diabetes patients selected randomly
      from the persons who did not return the questionnaire. Forty-one (76%) patients
      reported a 44.0 +/- 4.0% subjective improvement in their neuropathic pain. The
      overall improvement in pain was also significant on an analog scale of 10 (p <
      .01), and correlated well with the percent amelioration data (r2 = .65). These
      data suggest an effectiveness of electrotherapy in managing neuropathic pain as
      an adjunct to the analgesics. It appears to provide continued benefit as the
      responders have used this nonpharmacological treatment modality for an average
      period of 1.7 +/- 0.3 years.

PMID- 9638543
TI  - The effects of diabetes mellitus on the material properties of human metatarsal
      bones.
AB  - While some investigations have focused on the effect of diabetes on the material
      properties of connective tissue in both the human and animal model, no study to
      date has investigated the effects of the disease process on human metatarsal
      bones. This investigation compared the material properties of human metatarsal
      bones from young diabetic donors (51.3 +/- 8 years) and older nondiabetic donors
      (72.3 +/- 10 years). The results demonstrated no significant differences between
      the two groups. This would seem to suggest that the effects of aging are
      comparable to the effects of diabetes on the structural integrity of human
      metatarsal bones.

PMID- 9638537
TI  - Flow cytometric assays to detect platelet activation and aggregation in device
      implanted calves.
AB  - Cardiovascular device development often relies upon large-animal models to assess
      blood biocompatibility prior to initiating clinical trials. Unfortunately, the
      amount of information gleaned from such trials is limited by simple assays that
      do not take full advantage of immunotechnological advances that increasingly are
      applied in clinical studies. Thus we have developed and tested new flow
      cytometric techniques for measuring circulating activated bovine platelets and
      platelet microaggregates. Monoclonal antibodies (MAbs) raised against both
      activated and quiescent bovine platelets were incubated with control and PMA-or
      ADP-stimulated whole blood. Selected MAbs detected activated bovine platelets and
      platelet microaggregates in vitro with flow cytometry. Five calves implanted with
      one of two designs of nonpulsatile ventricular-assist devices (VADs) were
      followed with these assays prior to and during VAD implantation. Circulating
      activated bovine platelets and microaggregates increased after implantation in
      all animals and, alternatively, remained elevated or returned toward preimplant
      levels. Platelet activation percentages as detected temporally by three MAbs were
      correlated with one another, and platelet activation was correlated with
      microaggregate formation. In summary, these new methods for the sensitive
      measurement of circulating activated bovine platelets and microaggregates may
      provide valuable information for the development and assessment of future
      cardiovascular device designs.

PMID- 9638545
TI  - Reconstruction of hallux limitus deformity using a first metatarsal sagittal-Z
      osteotomy.
AB  - A sagittal-Z osteotomy was used for reconstruction of symptomatic grade I and
      grade II hallux limitus deformity in 10 patients using the Regnauld
      classification system. This surgical method was also used in a patient to
      reconstruct a structurally elevated first metatarsal as an adverse sequela of
      previous hallux valgus surgery. All patients exhibited evidence of radiographic
      metatarsus primus elevatus (MPE) and/or an anatomically elongated first
      metatarsal (EM). Linear comparison of first and second metatarsal length was
      performed in the transverse plane on dorsoplantar weightbearing radiographs. A
      long first metatarsal (positive metatarsal protrusion distance) was considered an
      anatomically elongated metatarsal. Metatarsus primus elevatus was evaluated by
      comparing the dorsal cortical margin of the first and second metatarsals and/or
      comparing the first metatarsal-cuneiform joint axis with the talonavicular joint
      axis. Metatarsus primus elevatus was therefore defined as a position of the
      dorsal cortical margin of the first metatarsal 5 mm superior to that of the
      second. A dorsal position of the first metatarsal-cuneiform joint axis in
      relation to the talonavicular joint axis also established MPE. A total of 11
      patients underwent a total of 13 procedures. There were eight excellent results
      (73%) and three good results (27%). There were no fair or poor results.

PMID- 9638546
TI  - Retrospective analysis of the Mau osteotomy and effect of a fibular
      sesamoidectomy.
AB  - The purpose of this study was to evaluate retrospectively outcomes of the Mau
      osteotomy for hallux abducto valgus deformity. Twenty-two patients were evaluated
      by the senior author on an average of 14 months (range, 3-34 months) following
      their surgery. Preoperative and postoperative intermetatarsal (IM) and hallux
      abductus (HA) angles were evaluated as well as range of motion of the first
      metatarsophalangeal joint and patient satisfaction. The mean preoperative IM and
      HA angles were 16.1 degrees and 35.8 degrees. The mean reduction in IM and HA
      angles was 10.5 degrees and 23.5 degrees, respectively. Joint range of motion was
      58 degrees of dorsiflexion (range, 42 degrees-80 degrees) and 11 degrees of
      plantarflexion (range, 0 degree-20 degrees). There were no cases of delayed
      healing or avascular necrosis. There were two patients (9%) with radiographic
      values consistent with hallux varus; however, neither patient had a clinical
      appearance of hallux varus and neither patient was displeased with the outcome.
      Ninety-one percent of patients returned to a soft shoe or sneakers in an average
      of 5.1 weeks following surgery. Eighty-two percent of patients had no pain at the
      time of their evaluation, and 96% of patients stated they were satisfied or very
      satisfied with the surgery. Comparing the subgroup of patients who underwent a
      Mau-Reverdin procedure with another subgroup undergoing a Mau-Reverdin fibular
      sesamoidectomy, there was a 3.7 degrees greater reduction of IM angle and 6.7
      degrees greater reduction in HA angle in the subgroup with the fibular
      sesamoidectomy.

PMID- 9638544
TI  - Talocalcaneal bar resection.
AB  - The purpose of this retrospective study is to report the author's experience with
      talocalcaneal bar resections in eight young patients, mean age 14.1 years, with a
      mean follow-up of 54 months (range, 36-136 months). All patients were submitted
      before surgery to conservative treatment during 20.3 months (range, 6-60 months)
      which consisted of nonsteroidal anti-inflammatory medication, physical therapy,
      short waves, and insoles. At follow-up, no recurrence and no secondary deformity
      of the foot were observed. Four patients were totally pain free with no
      restriction of activity, two patients had some pain during sport exercises, and
      one patient with bilateral involvement had pain after strenuous activities. The
      study evaluated the mobility of the subtalar joint at follow-up by comparing it
      with the healthy side. A total restoration of mobility was observed in four
      patients, partial in three, and limited residual mobility was observed in only
      one patient. Talocalcaneal bar resection is the treatment of choice in young
      patients after failure of conservative measures. In this population, there is no
      place for subtalar joint arthrodesis.

PMID- 9638547
TI  - Stabilization of the subluxed second metatarsophalangeal joint: flexor tendon
      transfer versus primary repair of the plantar plate.
AB  - Surgical treatment of the subluxed second metatarsophalangeal joint (MTPJ) has
      been a consistently frustrating problem for the foot and ankle surgeon. The
      plantar plate is the principal stabilizing structure of the second MTPJ and
      compromise to its integrity has been implicated as the cause of the subluxed
      second toe. Flexor tendon transfer has been reported as the mainstay of treatment
      to stabilize the subluxed second MTPJ. Recently, primary repair of the plantar
      plate has been advocated, yet no research exists comparing it to flexor tendon
      transfer. Eight freshly frozen lower extremity cadaver specimens were mounted on
      a custom-fabricated load frame. A vertical dorsally directed force was applied to
      the base of the proximal phalanx of the second toe via a pneumatic actuator to
      stimulate the Lachman test. Dorsal displacements of the proximal phalanx were
      measured with a linear variable distance transducer. This investigation examined
      the comparative strength of flexor tendon transfer versus primary repair of the
      plantar plate in stabilizing the second MTPJ. Results showed a significant
      difference between the transected plantar plate and the intact plantar plate.
      Displacements for the repair groups were similar to the intact plantar plate
      group and also significantly different from the transected plantar plate. Primary
      repair of the plantar plate is a viable alternative to flexor tendon transfer in
      stabilizing the second MTPJ with the advantage of addressing the pathology
      anatomically. Clinical studies are needed to substantiate these laboratory
      findings.

PMID- 9638548
TI  - A comparison of the efficacy of injectable dexamethasone sodium phosphate versus
      placebo in postoperative podiatric analgesia.
AB  - Forty-two patients undergoing identical bilateral foot surgery were evaluated in
      a double-blind study designed to evaluate the efficacy of injectable
      dexamethasone sodium phosphate versus placebo as an analgesic. Patients who had
      elective foot surgery on an outpatient basis received an injection of
      dexamethasone sodium phosphate in one foot and an equivalent injection of normal
      sterile saline in the contralateral foot. Both the patients and the surgeons were
      unaware of which foot was injected with each agent. The results suggest that
      there was not a difference in the patient perception of which foot was most
      painful. Forty-eight to 72 hours after surgery, 18 (44%) patients identified the
      foot that received steroid as less painful, 18 (44%) patients identified the foot
      that received placebo as less painful, and 5 (12%) patients did not perceive a
      difference. In addition, there was not a difference in outcome based on soft
      tissue or osseous procedures.

PMID- 9638549
TI  - Autogenous free dermal fat grafts in the surgical approach to plantar
      fibromatosis.
AB  - Plantar fibromatosis is a benign disorder of the foot in which there is fibrous
      tissue infiltration of the plantar aponeurosis and in some cases the overlying
      skin. Treatment is indicated for pain and functional gait disturbance. Even with
      wide fascial resection, recurrence with spreading, scarring, and continued
      discomfort can be a frustrating and difficult problem. Various techniques to
      lessen recurrence have included split-thickness skin grafting and Marlex mesh
      placement. However, these procedures have documented problems, including
      recurrence, foreign-body reaction, scarring, and inadequate soft-tissue coverage.
      The authors introduce dermal fat grafting following primary excision as a means
      to minimize recurrence while maintaining the anatomic architecture of the foot
      and preserving a soft, supple weightbearing surface with minimal scar tissue
      formation.

PMID- 9638550
TI  - Angiomatoid malignant fibrous histiocytoma: report of an unusual case with highly
      aggressive clinical course.
AB  - The authors report a case of angiomatoid malignant fibrous histiocytoma (AMFH),
      affecting a 9-year-old girl, with a highly aggressive clinical course. The tumor,
      noticed by the patient as a painless nodule in the dorsum of her left foot for 12
      months, recurred 8 months after initial excision, and despite wide local
      reexcision, metastasized 4 months later to the liver and lung, where it grew at
      an alarming rate, to the extent of occupying the entire left hemithorax in a
      period of 10 weeks and killed the patient 14 months after initial excision.
      Review of the literature showed that the culminated rates of recurrence,
      metastasis, and mortality for AMFH were 23.2%, 8.7%, and 4.3%, respectively,
      indicating that it is definitely a malignant neoplasm with a potentially fatal
      outcome.

PMID- 9638552
TI  - Diabetic foot infections.

PMID- 9638551
TI  - Lateral subtalar dislocation: review of the literature and case presentation.
AB  - Lateral subtalar joint dislocations are rare injuries which are usually the
      result of a violent eversional force, driving the talar head medially and
      displacing the rest of the foot laterally. Associated fractures and obstruction
      to closed reduction are more common with lateral than medial dislocations.
      Avascular necrosis of the talus and navicular as well as subtalar instability may
      result from these injuries. Severe post-traumatic subtalar arthritis may warrant
      triple arthrodesis. Prompt closed reduction of lateral subtalar dislocation is
      recommended to avoid soft-tissue or neurovascular compromise. A short period of
      immobilization limits loss of subtalar range of motion. Open reduction may be
      required, particularly with entrapment of the posterior tibial tendon or
      obstructing fracture fragments. A case of lateral subtalar joint dislocation is
      presented.

PMID- 9638553
TI  - The simple "plumb line" osteotomy guide.

PMID- 9638556
TI  - Sketching the framework for a history and sociology of homosexualities in the
      Nordic countries.

PMID- 9638554
TI  - Flexor hallucis longus dysfunction.

PMID- 9638557
TI  - State policy, popular discourse, and the silence on homosexual acts in early
      modern Sweden.
AB  - In Sweden, homosexual acts between men were mentioned in secular law for the
      first time in 1608. Despite the explicit criminalization, very few trials are
      known from the seventeenth and eighteenth centuries, and the new National Law
      Code of 1734 contained no sanction at all. The central issue of this essay is how
      the insignificant number of court cases and the seemingly very limited judicial
      interest in the issue of sodomy in Early Modern Sweden should be interpreted. The
      silence of the new law is explained by a shift in the official policy from
      deterrence to a policy of silence, but the low number of court cases was foremost
      dependent on a lacking actualization and problematization of homosexual acts in
      the Swedish popular discourse on sexuality, gender, and prestige. Finally, it is
      argued that this undeveloped popular discourse probably also corresponded to a
      meagre and rather restricted sexual practice.

PMID- 9638558
TI  - A premodern legacy: the "easy" criminalization of homosexual acts between women
      in the Finnish Penal Code of 1889.
AB  - Homosexual acts between women were criminalized in Finland in the 1889 Penal Code
      which also criminalized men's homosexual acts for the first time explicitly in
      Finnish legislation. The inclusion of women in the Penal Code took place without
      much ado. In the article it is argued that the uncomplicated juxtaposing of men
      and women was due to the legacy of a cultural pattern where man and woman, as
      categories, were not in an all-pervasive polarity to each other, for example, in
      sexual subjectivity. A cultural pattern of low gender polarization was typical of
      preindustrial rural culture, and it can help us apprehend also certain other
      features in contemporary Finnish social and political life, for example, women
      obtaining a general franchise and eligibility for the parliament first in the
      world, in 1906. A modern image of "public man" and "private woman" was only
      making its way in Finnish society; hence, there was not much anxiety at women's
      entry in politics, or, for that matter, at their potential for (homo)sexual
      subjectivity becoming recognized publicly in criminal law.

PMID- 9638559
TI  - Creating their own private and public: the male homosexual life space in a Nordic
      city during high modernity.
AB  - In this article I describe the male homosexual life space in a Nordic city during
      the decades around the Second World War. It consisted almost entirely of outdoor
      places such as parks, public conveniencies, and streets. It included, in Delph's
      (1978) words, not only erotic, but also cultural and social oases, fostering an
      extensive and varied social life and a growing community. Most of this outdoor
      space was invisible to those other than the participants. It had its own
      differentiation of, and meanings for, "public" and "private." A poor economy,
      overcrowding, and the classical modern city helped shape the location and design
      of the male homosexual life space, as did the participation of many men who did
      not look upon themselves as "homosexual." During this period, and especially
      after the Second World War, this life space began to change in a direction
      pointing towards that of today, that is, towards less outdoor life and more life
      in homes and semipublic indoor spaces. Better economy, the rise of the welfare
      state, and diminished overcrowding furthered this movement. Among other things,
      these changes stimulated the withdrawal of men who did not see themselves as
      "homosexual." The transformation of the city into the spread out, suburbanized
      city, with segregation of various functions, contributed to the development, as
      did the obstruction of parks and toilets as meeting places by public authorities.
      The law reform of 1944, which decriminalized homosexual erotic acts between
      adults, was also of importance.

PMID- 9638560
TI  - The power of confession: the role of the criminal law and courtpractices in the
      production of knowledge concerning sexuality between women: Finland, in the
      1950s.
AB  - The article discusses a number of court cases on women's same-sex fornication in
      the Finnish countryside in the 1950s. Based on a close reading of the minutes of
      the police investigations and the court records, the article shows how the notion
      of sexual acts between women, and the notion of certain modes of conduct as
      "sexual," were constructed in these proceedings. The authorities could conceive
      sexual relations only in terms of the "heterosexual matrix" (cf. Judith Butler);
      hence they assumed that the alleged sexual encounters between the women were a
      copy of a heterosexual sexual intercourse. As for the accused women, many of whom
      were connected with a Christian sect, they often insisted that the physical
      expressions of their mutual affection were not sexual, and they opposed the
      interpretation that their conduct might have anything to do with homosexuality,
      which they considered a pathology. As the women nevertheless often ended up
      repenting their conduct, they reproduced the conventional image of sexually
      passive "soft" woman, though perhaps partly because of strategic reasons.

PMID- 9638561
TI  - A dung beetle in distress: Hans Christian Andersen meets Karl Maria Kertbeny,
      Geneva, 1860: some notes on the archaeology of homosexuality and the importance
      of tuning.
AB  - In 1860, the Danish fairy tale writer (whose fairy tales are perhaps primarily
      for grown-ups) met Karl Maria Kertbeny--who is supposed to have coined the term
      "homosexual" (first used in a private manuscript in 1868). The meeting caused
      immense despair in Andersen; yet what happened has remained a mystery. A careful
      study of Andersen's fairy tales and papers, however, provides a clue to an
      answer. The article deals with the horrors of being labelled; but it also
      discusses labelling as merely a minor part of what goes on in the making of the
      modern homosexual. Above all, Andersen's moods seem important and identifiable to
      us as homosexuals; more generally, they seem stirringly close to postmodern
      existence.

PMID- 9638562
TI  - Identity, place, and erotic community within gay leather culture in Stockholm.
AB  - There has been much recent attention to the relationship between the construction
      of place, identity, and the body. This paper examines some of these themes in a
      presentation of the gay leather scene in Stockholm, Sweden. Based on ethnography
      of Stockholm's only true leather club, it shows how identity and spatial location
      are implicated in one another. It also looks at social and cultural processes of
      containment and dispersion within leather culture, the creation of erotic bodies,
      and forms of erotic interaction. These processes are seen as reflecting features
      of the wider Swedish gay scene and society in general, which is sometimes less
      tolerant than it is imagined to be. Aspects of current and possible future
      transformations of leather culture and style are also briefly considered.

PMID- 9638563
TI  - Dressing up in power: Tom of Finland and gay male body politics.
AB  - On one hand, the article examines ways in which Tom of Finland's drawings
      participated in discursive formations that created and disseminated the gay macho
      look. "Tom's men" appropriated these pictures to make gay identities visible in
      their bodies, and created potentially resisting meanings. On the other hand, the
      author explores the meanings of Tom's drawings, particularly in relation to
      discourses of sexuality, gender, and race. He argues for the multiplicity of
      power and for ambivalent interaction of resistance and oppression in Tom's
      drawings. Tom's pictures draw attention to an idea, derived from Michel Foucault,
      that power and resistance are to be found in one and the same place. Although
      ways in which these images are used may give rise to subversive meanings they
      also circulate racist, sexist, and fascist discourses that contradict their
      potentially radical meanings. Indeed, the problem with the transgressive
      pleasures is that transgression may help to sustain the limits that are supposed
      to be crossed and deconstructed by a transgressor.

PMID- 9638564
TI  - The ambiguity of lesbian and gay marriages: change and continuity in the symbolic
      order.
AB  - The article discusses the Registered Partnership Act, passed in Norway in 1993,
      which has given gay and lesbian couples a right to register their relationship
      and to obtain many of the legal rights that heterosexual couples have. The
      article argues that the introduction of the Act is a product of, among others,
      cohabitation having become more legitimate as a life-form also among
      heterosexuals. The practical consequences of the Act have been modest, with
      relatively few couples having registered their relationship. The article suggests
      that the symbolic rather than the practical aspects of the Act have been
      important, and even then, the symbolic effect of the Act is equivocal. The new
      formal rights of gays and lesbians are of decreasing social and symbolic value,
      as new boundaries for legitimate life-forms are being demarcated elsewhere: While
      legislation on marriage concedes that personal relationships are a private
      matter, the right to have and to foster children is regarded as an issue where
      society at large should have a say. This view is also reflected in the
      restrictions that the Registered Partnership Act has placed on gay and lesbian
      couples in having children of their own.

PMID- 9638565
TI  - Gay and lesbian politics: assimilation or subversion: a Danish perspective.
AB  - The article discusses the trajectory of lesbian and gay politics in Denmark, from
      the 1970s to the 1990s. It argues that, as part of the social and cultural
      change, marriage has become an empty institution; hence the ostensibly remarkable
      progress that gay and lesbian couples have also been conceded a marriage-like
      status. However, while pursuing this right, lesbian and gay organizations may
      have been too compliant with middle-class ideals of "decent" lifestyles; entering
      a registered partnership may become a new norm which excludes "less respectable"
      modes of homosexual lifestyles. The radical potential of homosexuality as a
      manifestation of the variety of lifestyles should not be jettisoned in the name
      of politics of assimilation.

PMID- 9638566
TI  - The ethics of care: a feminist virtue ethics of care for healthcare
      practitioners.
AB  - In this paper I seek to distinguish a feminist virtue ethics of care from (1)
      justice ethics, (2) narrative ethics, (3) care ethics and (4) virtue ethics. I
      also connect this contemporary discussion of what makes a virtue ethics of care
      feminist to eighteenth and nineteenth century debates about male, female, and
      human virtue. In conclude that by focusing on issues related to gender--primarily
      those related to the systems, structures, and ideologies that create and sustain
      patterns of male domination and female subordination--we can begin to appreciate
      that true care and bona-fide virtue can flourish only in societies that treat all
      persons with equal respect and consideration.

PMID- 9638567
TI  - Impartial principle and moral context: securing a place for the particular in
      ethical theory.
AB  - This essay critically assesses two strategies of accommodation used by defenders
      of impartialism in ethics to argue that the care orientation represents no
      genuine challenge to impartialist theoretical paradigms. One strategy focuses on
      impartiality as a constraint on moral deliberation, the other as a constraint on
      moral justification. While highlighting respects in which the commitment to
      impartiality is more consonant with the care orientation than many advocates of
      care have acknowledged, this essay attempts to clarify crucial ways in which each
      accommodationist strategy fails, thus locating some of the more important
      contributions and challenges the care orientation offers to moral theory.

PMID- 9638568
TI  - Care theory and the ideal of neutrality in public moral discourse.
AB  - In this paper I argue that Care theory has the resources to offer an insightful
      and original theoretical perspective on issues in medical ethics. The paper
      begins with a discussion of the sort of theory Care is, and argues that it
      closely resembles virtue theory. After a discussion of common features of Care
      theories, I respond to a few of the criticisms that have been levied against the
      theory. The final section of the paper is a discussion of the question of
      neutrality in public moral discourse. Care theory is not a neutral theory with
      regard to questions of the nature of the good life for humans, but I argue that
      this should not preclude Care from playing a part in the public debate over
      policy decisions.

PMID- 9638569
TI  - Care: from theory to orientation and back.
AB  - In this paper, I urge that the very real lessons Carol Gilligan's work in moral
      psychology offer to moral philosophy can best be appreciated if we take seriously
      the gap between the two disciplines. The care and justice perspectives Gilligan
      explores are psychological orientations, and orientations are defined as much by
      matters of emphasis, selectivity of interpretation, and gestalt as they are by
      propositional commitment. As such, I argue, their contribution to moral theory is
      best seen as stances from which to do theory, rather than as constituting ready
      made theories themselves. In pursuing this train of thought, I examine how
      Gilligan's work has developed over time and how, in the end, we should understand
      the juxtaposition between the two orientations.

PMID- 9638570
TI  - The place of care in ethical theory.
AB  - The concept of care and a related ethical theory of care have emerged as
      increasingly important in biomedical ethics. This essay outlines a series of
      questions about the conceptualization of care and its place in ethical theory.
      First, it considers the possibility that care should be conceptualized as an
      alternative principle of right action; then as a virtue, a cluster of virtues, or
      as a synonym for virtue theory. The implications for various interpretations of
      the debate of the relation of care and justice are then explored, suggesting
      three possible meanings for that contrast. Next, the possibility that care
      theorists are taking up the debate over the relation between principles and cases
      is considered. Finally, it is suggested that care theorists may be pressing for
      consideration of an entirely new question in moral theory: the assessment of the
      normative appropriateness of relationships. Issues needing to be addressed in an
      ethic of relationships are suggested.

PMID- 9638571
TI  - Advances in biopharmaceutical analysis in the People's Republic of China 1995
      1997.
AB  - The present paper is the third biannual review in succession to the author's
      previous publications (Z.L. Qin, Advances in biopharmaceutical analysis in the
      People's Republic of China: 1991-1993, J. Pharm. Biomed Anal. 13, 1995, 1-7 and
      Z.L. Qin, Advances in biopharmaceutical analysis in the People's Republic of
      China: 1993-1995, J. Pharm. Biomed. Anal. 14, 1996, 1395-1403), regarding the
      methodological study and progress in biopharmaceutical analysis by RP-HPLC, GC
      and GC-MS selected from relative journals between April 1995 and March 1997 in
      P.R. China. The published methods were widely adopted in pharmacokinetic and
      metabolic studies. Investigation on drug metabolism were conducted more deeply,
      both in vitro and in vivo, for searching the structure of metabolites and drug
      metabolic pathways. The use of high performance CZE as a new trend for the
      analysis of drugs and metabolites in biofluids was also reported.

PMID- 9638572
TI  - Validation of bioanalytical chromatographic methods.
AB  - A strategy is discussed for the validation of chromatographic methods that are
      developed to quantify drugs in biological matrices. Both the validation
      terminology and the hypothesis testing are briefly reviewed. The emphasis is on
      the design of the experiments required to allow a reliable conclusion about
      acceptance or rejection of the bioanalytical method. In particular, it is
      explained how to evaluate the calibration line, devise experiments to estimate
      precision and bias and how to determine the stability of the analyte between the
      time of the sample collection and the analysis of the processed sample.

PMID- 9638573
TI  - Moisture determination in hygroscopic drug substances by near infrared
      spectroscopy.
AB  - The moisture level in a hygroscopic drug substance was successfully determined by
      near infrared spectroscopy using coulometric Karl Fischer titration as the
      reference method. The importance of sample handling and proper application of the
      reference technique are stressed for this difficult sample type. Samples were
      prepared with moisture levels from 0.5 to 11.4% (w/w) and reflectance spectra
      were collected over the spectral range 1100-2500 nm. Calibration models were
      built using partial least squares (PLS) regression analysis. Optimum models were
      found by choosing proper spectral ranges and number of PLS factors. The best
      calibration models were built using first derivative spectra, a spectral range of
      1850-1936 nm and 5 PLS factors. The corresponding standard error of prediction
      was 0.11% (w/w) water.

PMID- 9638574
TI  - Comparison of p-fluoroketorolac and [18O3]ketorolac for use as internal standards
      for the determination of ketorolac by gas chromatography/mass spectrometry
      (GC/MS).
AB  - A chemical and a stable-isotope analog, p-fluoroketorolac and [18O3]ketorolac
      respectively, were directly compared for applicability as internal standards for
      the determination of ketorolac in plasma samples using gas chromatography/mass
      spectrometry (GC/MS) with selective-ion-monitoring detection, following
      derivatization to form the methyl esters. This comparison involved analyzing
      ketorolac calibration standards and spiked plasma samples that contained both
      internal standard candidates. The response for ketorolac and each internal
      standard was monitored simultaneously and electronically integrated peak heights
      were obtained. Thus, for each analysis performed, a response ratio was obtained
      for each internal standard relative to an identical ketorolac response. Linearity
      of response for ketorolac calibration standards and accuracy for spiked plasma
      sample analysis were compared using each internal standard. The use of
      [18O3]ketorolac as the internal standard provided superior accuracy data for the
      analysis of ketorolac in plasma samples.

PMID- 9638575
TI  - Spectrofluorometric determination of piroxicam.
AB  - The spectrofluorometric determination of piroxicam [4-hydroxy-2-methyl-N-(2
      pyridyl)-2II-1,2-benzothiazine-3-carboxam ide-1, 1-dioxide] in pharmaceutical
      tablets is described. It involves excitation at 330 nm of an acid solution (HNO3
      0.5 M) of the drug, and measurement of the fluorescence intensity at 440 nm. The
      linear range is 0.01-1.25 micrograms ml-1.

PMID- 9638576
TI  - Simultaneous determination of dextromethorphan HBr and bromhexine HCl in tablets
      by first-derivative spectrophotometry.
AB  - A rapid, simple and direct assay procedure based on first-derivative
      spectrophotometry, using a zero-crossing and peak-to-base measurement at 234 and
      324 nm, respectively, has been developed for the specific determination of
      dextromethorphan HBr and bromhexine HCl in tablets. Calibration graphs were
      linear with the correlation coefficients of 0.9999 for both analytes. The limit
      of detections were 0.033 and 0.103 microgram ml-1 for dextromethorphan HBr and
      bromhexine HCl, respectively. A HPLC method has been developed as the reference
      method. The results obtained by the first-derivative spectrophotometry were in
      good agreement with those found by the HPLC method.

PMID- 9638577
TI  - Enzyme-linked immunosorbent assay for TA-2005-glucuronide in human plasma.
AB  - A sensitive enzyme-linked immunosorbent assay (ELISA) for TA-2005-glucuronide, a
      main metabolite of new adrenergic beta-receptor agonist TA-2005, has been
      investigated without prior deconjugation. Coupling of the hapten with bovine
      serum albumin (BSA) or beta-D-galactosidase was carried out by the N
      hydroxysuccinimide ester method. An anti-TA-2005-glucuronide antiserum was
      obtained from guinea pig immunized with the hapten-BSA conjugate. The ELISA was
      based upon a competitive assay in which the separation of bound from free
      fraction was performed by the double antibody technique using rabbit anti guinea
      pig immunoglobulin antibody adsorbed to microtiter plates. A satisfactory
      standard curve for the ELISA of TA-2005-glucuronide was observed in the range of
      30 pg-3 ng ml-1 using 25 microliters of human plasma. Inter-day and intra-assay
      variations were 7.0-17.5% and 1.0-11.7% respectively. The recoveries of TA-2005
      glucuronide spiked to plasma samples were 95.5-120% (inter-assay) and 96.0-123.3%
      (intra-assay). The cross-reactivities of the prepared antiserum with the related
      compound of TA-2005-glucuronide were quite low though there was a considerable
      cross-reaction with TA-2005. However, TA-2005-glucuronide could be easily
      separated from TA-2005 by a simple pretreatment of the plasma sample with a C18
      cartridge column. This method was applied to the determination of TA-2005
      glucuronide in human plasma samples for the evaluation of the pharmacokinetics of
      TA-2005. From the results, it was demonstrated that the ELISA developed was
      useful for the determination of TA-2005-glucuronide in human plasma and that the
      method was applicable to pharmacokinetic studies in humans.

PMID- 9638578
TI  - Simultaneous determination of an active metabolite and open-ring metabolites by
      high performance liquid chromatography and pharmacokinetic studies of a penem
      antibiotic, FCE22891, in dogs.
AB  - A sensitive high performance liquid chromatographic method for the simultaneous
      determination of an active metabolite (FCE22101) and open-ring metabolites (P1,
      P2) of a penem antibiotic, FCE22891, in dog plasma was developed. Plasma samples
      were pretreated only by ultrafiltration for the determination of the metabolites.
      The filtrates were directly analyzed by a reversed-phase high-performance liquid
      chromatographic system using a two-sided bracketing injection technique. The
      quantitation limits of FCE22101, P1 and P2 were 0.03, 0.1 and 0.15 microgram ml
      1, respectively. Analysis of the spiked plasma samples demonstrated the good
      accuracy and precision of the method. The proposed method was applied to the
      pharmacokinetic studies of an active metabolite and open-ring metabolites after
      oral administration of a penem antibiotic, FCE22891, in dogs. In addition, the
      plasma levels of unchanged FCE22891 and the possible changes of formaldehyde and
      acyl-L-carnitine levels in plasma, which will be generated from the ester group
      of FCE22891, were also investigated.

PMID- 9638579
TI  - Flow-injection spectrophotometric determination of diclofenac sodium in
      pharmaceuticals and urine samples.
AB  - A sensitive and fast flow-injection spectrophotometric method for the
      determination of diclofenac sodium based on the formation of coloured compound
      with Ce(IV)-3-methyl-2-benzothiazolinone hydrazone hydrochloride (MBTH) in H2SO4
      3 x 10(-2) M medium is proposed. Using the peak height as a quantitative
      parameter diclofenac was determined at 580 nm over the range 0.20-8.0 micrograms
      ml-1. The proposed method was successfully applied to the determination of
      diclofenac in pharmaceuticals and urine samples.

PMID- 9638580
TI  - Polarographic determination of some penicillins through nitrosation.
AB  - Direct current and differential pulse polarography DPP were used for the
      determination of three penicillins, namely, ampicillin, benzylpenicillin and
      carbenicillin, in pure form and in their dosage forms. The method is based upon
      treatment of penicillins with nitrous acid followed by polarographic measurement
      of the produced derivatives polarographically. The nitroso derivatives formed
      exhibited reduction waves over the whole pH range in Britton-Robinson buffers.
      The waves were characterized as being diffusion-controlled and free from
      adsorption phenomena. The current-concentration plots were rectilinear over the
      concentration range 8-200 and 2-160 micrograms ml-1 for DCt and DPP,
      respectively, for all the studied compounds. The proposed method was further
      applied to determine penicillins in pharmaceutical preparations, and the results
      obtained were in good agreement with those given by the companies.

PMID- 9638581
TI  - Oxidation of recombinant methionyl human granulocyte colony stimulating factor.
AB  - The oxidation of methionine residues in recombinant methionyl human granulocyte
      colony stimulating factor with hydrogen peroxide has been investigated. Kinetic
      data of the oxidation were obtained by using reversed phase-high performance
      liquid chromatography. The stability-indicating capability of this system was
      confirmed with micellar electrokinetic capillary chromatography. In the pH range
      1.9-7.5, the kobs value for the oxidation process is constant. Above pH 7.5, kobs
      tends to increase with increasing pH. In the pH range 1.9-11.8, four oxidation
      products were detected in RP-HPLC. Mass spectrometric analysis revealed that one
      mono-, one di- and two trioxidation products were formed. Using the cyanogen
      bromide cleavage method the nature of the oxidation products was determined. The
      mono-oxidation product is the protein with Met121 oxidized, while the dioxidation
      product has oxidized Met121 and Met126 residues. The trioxidation products are
      the proteins with Met121, Met126 and Met137 or Met0, Met121 and Met126 oxidized.

PMID- 9638582
TI  - Determination of N3-methyl-5'-deoxy-5-fluorouridine, a novel metabolite of
      doxifluridine, in body fluids by high performance liquid chromatography.
AB  - A high performance liquid chromatography method for the determination of N3
      methyl-5'-deoxy-5-fluorouridine, a possible metabolic product of the anticancer
      pro-drug 5'-deoxy-5-fluorouridine, in human serum and urine is described. Sample
      treatment involved addition of internal standard (5-bromouracil) and protein
      precipitation with ammonium sulphate (serum samples) followed by liquid-liquid
      extraction with ethyl acetate-isopropanol (90:10, v/v). The average recovery at
      0.5 mg ml-1 level was (80 +/- 4%). A linear response extending over two decades
      of concentration was observed. Detection limits of 50 and 100 ng ml-1 were
      obtained in serum and urine, respectively.

PMID- 9638583
TI  - Electrochemical reduction of metronidazole at activated glassy carbon electrode
      and its determination in pharmaceutical dosage forms.
AB  - A voltammetric method has been developed for the determination of metronidazole
      in dosage forms. The method is based on the electrochemical reduction of the drug
      at a glassy carbon electrode activated by applying a new pretreatment. The
      influence of pH, concentration, scan rate and presence of organic solvent and
      surfactant has been studied. The current is proportional to the concentration and
      permits the drug to be determined in the concentration range 2 x 10(-6)-6 x 10(
      4) M in Britton-Robinson buffer (pH 10). Furthermore, results obtained by the
      proposed method have been compared with USP XXIII procedure which involves a HPLC
      method.

PMID- 9638584
TI  - A novel technique for visualizing the intracellular localization and distribution
      of transported polyamines in cultured pulmonary artery smooth muscle cells.
AB  - The use of a combination of monofluorescein adducts of spermidine (FL-SPD) and
      spermine (FL-SPM) with confocal laser scanning microscopy (CLSM) provides a
      useful means for monitoring the fate and time-dependent changes in the
      distribution of transported polyamines within living cells. Polyamine-fluorescein
      adducts were synthesized from fluorescein isothiocyanate and the appropriate
      polyamine. Monofluorescein polyamine adducts (ratio 1:1) were isolated using thin
      layer chromatography, and the structure and molecular weight of the
      monofluorescein polyamine adducts were confirmed using NMR and mass spectroscopy,
      respectively. The covalent linkage of the fluorescent adduct moiety to SPD and
      SPM did not influence their rate of uptake by bovine pulmonary artery smooth
      muscle cells (PASMC). Similar to 14C-SPD and 14C-SPM, the rate of uptake of 14C
      FL-SPD and 14C-FL-SPM in PASMC was temperature-dependent. Treatment for 24 h with
      difluoromethylornithine (DFMO), a selective blocker of the enzyme ornithine
      decarboxylase and an inducer of the polyamine transport system, significantly
      increased the cellular uptake of 14C-FL-SPD and 14C-FL-SPM compared to that of
      control cells. When compared to control cells, treatment of PASMC with the
      pyrrolizidine alkaloid monocrotaline for 24 h also significantly increased the
      cellular uptake of 14C-FL-SPD and 14C-FL-SPM. On the other hand, 24 h treatment
      of PASMC with a polymer of SPM, a selective blocker of the polyamine transport
      system, or with free spermine, markedly reduced the cellular accumulation of 14C
      FL-SPD and 14C-FL-SPM. After a 20-min treatment of PASMC with FL-SPD or FL-SPM,
      CLSM revealed that adduct fluorescence was localized in the cytoplasm of living
      cells. Treatment with DFMO increased the cytoplasmic accumulation of both FL-SPD
      and FL-SPM. In addition, the fluorescence observed in the cytoplasm of chinese
      hamster ovary cells (CHO) was significantly higher than that detected in the
      cytoplasm of their polyamine transport deficient variants (CHOMGBG). The results
      of this study provide the first evidence of the utility of a novel method for
      visualizing the uptake, distribution, and cellular localization of transported
      polyamines in viable cultured mammalian cells.

PMID- 9638585
TI  - Determination of (S)(-)-cathinone by spectrophotometric detection.
AB  - Previous studies on the Khat plant (Catha edulis, Celastraceae) illustrated the
      importance of using freshly harvested young shoots and leaves such that
      cathinone, the principle active component and Schedule I controlled drug
      contained within the plant, could be suitably isolated and identified. The
      purpose of this work was to develop a quantitative analytical technique for the
      determination of cathinone. The proposed method is based on treating the
      reductant cathinone with copper(II)-neocuproine reagent in sodium acetate
      buffered medium followed by measuring the absorbance of the copper(I)-neocuproine
      complex at 455 nm. The calibration plot is linear in the range 0.08-25 micrograms
      ml-1 with a detection limit of 0.08 microgram ml-1. The precision of the method,
      expressed as the relative standard deviation, is 1.35% for 10 micrograms ml-1
      cathinone. Good recoveries have been obtained in applying the method to the
      analysis of cathinone in Khat leaves.

PMID- 9638586
TI  - Acidic hydrolysis of bromazepam studied by high performance liquid
      chromatography. Isolation and identification of its degradation products.
AB  - A kinetic study on the acidic hydrolysis of bromazepam was carried out in 0.01 M
      hydrochloric acid solution at 25 and 95 degrees C. A reversed-phase HPLC method
      was developed and validated for the determination of bromazepam and its
      degradation products. Bromazepam degraded by a consecutive reaction with a
      reversible first step. Two degradation products were isolated and identified by
      infrared, 1H and 13C nuclear magnetic resonance and mass spectroscopy.
      Spectroscopic data indicated that N-(4-bromo-2-(2-pyridylcarbonyl)phenyl)-2
      aminoacetamide was the intermediate degradation product of this acid hydrolysis,
      whereas 2-amino-5-bromophenyl-2-pyridylmethanone was the final one. Therefore,
      the mechanism of this acid-catalysed hydrolysis involved initial cleavage of the
      4,5-azomethine bond, followed by slow breakage of the 1,2-amide bond. Statistical
      evaluation of the HPLC method revealed its good linearity and reproducibility.
      Detection limits were 3.8 x 10(-7) M for bromazepam, 6.25 x 10(-7) M for the
      intermediate and 8.16 x 10(-7) M for the benzophenone derivative.

PMID- 9638587
TI  - HPLC analysis of pharmaceutical estrogens in raw materials and dosage forms.
AB  - The use of HPLC with fluorescence detection (lambda ex = 280 nm; lambda em = 410
      or 312 nm) in combination with a postcolumn on line photochemical derivatization
      was investigated for the analysis of conjugated and unconjugated estrogens and
      their correlated impurities. The column effluents were subjected on-line to UV
      irradiation (254 nm) and the photo induced modifications were useful for the
      identification of the various estrogens. The proposed HPLC methods were
      successfully applied to the analysis of commercially available conjugated
      estrogens (raw materials and pharmaceuticals) and estrogen samples. The assays
      results relative to the pharmaceutical formulations were in agreement with those
      obtained by a reference HPLC method with UV detection (lambda = 280 nm).

PMID- 9638588
TI  - Determination of terbutaline based on oxidation by voltammetry.
AB  - A voltammetric study of the oxidation of terbutaline has been carried out at an
      activated glassy carbon electrode. The compound was oxidized irreversibly at high
      positive potential. The response was evaluated with respect to pH, scan rate,
      nature of the buffer and other variables. The peak current, at about 0.8 V
      (versus a saturated calomel electrode), was proportional to the terbutaline
      concentration in the range of 8 x 10(-6)-8 x 10(-4) M in phosphate buffer pH 6.0.
      This method was applied, without any interferences from the excipients, to
      determine the drug in a tablet dosage form.

PMID- 9638589
TI  - Field method for the micro-quantitative determination of tetracycline in human
      blood serum.

PMID- 9638590
TI  - Effect of .OH scavenging action by non-SH-containing angiotensin converting
      enzyme inhibitor imidaprilat using microdialysis.
AB  - We examined the effect of non-SH-containing angiotensin converting enzyme (ACE)
      inhibitor imidaprilat on hydroxyl radical (.OH) generation using microdialysis.
      Salicylic acid in Ringer's solution containing sodium salicylate (0.5 n mol
      microL-1 min-1) was infused directly through a microdialysis probe to detect the
      generation of .OH as reflected by the formation of 2,3-dihydroxybenzoic acid
      (DHBA) in the myocardium of anesthetized rats. We compared the ability of two non
      SH-containing ACE inhibitors (imidaprilat and enalaprilat) with an -SH-containing
      ACE inhibitor (captopril) to scavenge the .OH. When iron (II) was administered to
      animals pretreated with these three ACE inhibitors, a decrease in 2,3-DHBA of all
      three compounds was observed, as compared with the iron (II) only-treated group.
      All three ACE inhibitors were able to scavenge .OH generated by the action of
      iron (II). However, imidaprilat is a free radical scavenger more potent than
      enalaprilat. These results suggested that ACE inhibitors are probably not only
      related to the presence of the SH radical.

PMID- 9638591
TI  - Involvement of AMPA receptors in posterior locomotor activity in the rabbit: an
      in vivo study.
AB  - Although AMPA receptors are known to be widely involved in excitatory synaptic
      neurotransmission at the spinal level, very little is known about their role in
      modulating motor activity in mammals. In curarized decerebrate or spinalized
      rabbit preparations, fictive locomotion was monitored on hindlimb nerves after
      either activation or blockade of AMPA receptors. In decerebrate preparations, the
      administration of the antagonist, NBQX (3.5 mg/kg i.p.) or the agonist, AMPA (0.5
      mg/kg i.v.) produced, in both cases, a depression of locomotor activities induced
      by stimulation of cutaneous afferents (evoked locomotor activity). This potent
      effect was transient with AMPA (recovery after 20 min) and followed by the
      occurrence of spontaneous locomotor sequences, while no recovery was observed
      with NBQX treatment. In spinal preparations where a continuous 'spontaneous'
      locomotor activity resulted from the pharmacological activation of noradrenergic
      descending pathways (nialamide-DOPA pretreatment), the same drugs injected at
      higher doses (5 mg/kg NBQX i.p. and 1 mg/kg AMPA i.v.) only weakly affected the
      frequency of 'spontaneous' and evoked locomotor bursts while they exerted
      inhibitory and facilitatory effects on the burst amplitude respectively. The
      results suggest that AMPA receptors are involved at spinal level: 1) in direct
      mediation of cutaneous afferent excitatory effects on the posterior locomotor
      generators (pLG); 2) in indirect mediation of a supraspinal descending inhibition
      controlling, likely presynaptically, the cutaneous afferent activation; and 3) in
      transmission to motoneurons of the output signals from the pLG. Finally, tight
      spinal interactions between potent descending noradrenergic pathways and spinal
      AMPA neurotransmission were disclosed.

PMID- 9638592
TI  - Opioid peptide involvement in the bulbar inhibition of electrodermal activity in
      the cat.
AB  - By analogy with supraspinal and spinal inhibitory controls of pain, it was
      hypothesized that an opioid mechanism could be involved in the bulbar inhibitory
      control of the electrodermal activity. This activity was evoked as skin potential
      responses on the footpads of 13 cats by the central tegmental field stimulation
      (control responses) and inhibited by the simultaneous stimulation of bulbar
      reticular formation (experimental responses). Then, naloxone, an opioid peptide
      antagonist, was injected intravenously or intrathecally and its effects were
      analyzed on both control and experimental responses. Intravenous injections of
      naloxone increased significantly the amplitude of experimental responses from 6
      to 12 min after the injection and had no effect on the amplitude of control
      responses. Intrathecal injections of naloxone induced significant increases of
      amplitude of experimental responses from 6 to 42 min after the injection. These
      results showed that a spinal opioid peptide link could be involved in bulbar
      inhibition mechanisms of electrodermal activity.

PMID- 9638593
TI  - Imidazoline receptors of the paraventricular nucleus on the pressor response
      induced by stimulation of the subfornical organ.
AB  - In the present experiments we investigated a possible involvement of imidazoline
      receptors of the paraventricular nucleus (PVN) of the hypothalamus on the pressor
      effects of the angiotensin II (ANG II) injected into the subfornical organ (SFO),
      in male Holtzman rats (250-300 g) with a cannula implanted into the third
      ventricle (3rdV), PVN and SFO. At first we tested the participation of alpha 2
      and imidazoline agonist and antagonist compounds on the pressor effect of ANG II
      injected into the 3rdV. Based on the results we may conclude that clonidine
      associated with rilmenidine was able to block the hypertensive response to ANG
      II. The ANG II (20 pmol) injected into SFO induced a robust increase in blood
      pressure (37 +/- 2 mmHg). Isotonic saline (0.15 M) NaCl did not produce any
      change in blood pressure (5 +/- 2 mmHg). The injection of rilmenidine (30
      micrograms/kg/1 microL), an imidazoline agonist agent injected into PVN before
      ANG II injection into SFO, blocked the pressor effect of ANG II (5 +/- 2 mmHg).
      Also, the injection of idazoxan (60 micrograms/kg/microL) before rilmenidine
      blocked the inhibitory effect of rilmenidine on blood pressure (39 +/- 4 mmHg).
      The injection of clonidine (20 nmol/microL) prior to ANG II into the 3rdV
      produced a decreased in arterial blood pressure (37 +/- 2 mmHg) to (15 +/- 4
      mmHg). The injection of yohimbine (80 nmol/microL) prior to clonidine blocked the
      effect of clonidine on the effect of ANG II (27 +/- 2 mmHg). The injection of
      rilmenidine prior to ANG II also induced a decrease in arterial blood pressure
      (10 +/- 3 mmHg). The injection of idazoxan prior to rilmenidine also blocked the
      inhibitory effect of rilmenidine (24 +/- 3 mmHg). In summary, the present study
      demonstrated that rilmenidine decreases the hypertensive effect of ANG II, with
      more potency than clonidine, even when injected into 3rdV or PVN. This study
      established that the PVN interacts with SFO by imidazoline receptors in order to
      control the arterial blood pressure.

PMID- 9638594
TI  - Glucose-induced mobilisation of intracellular Ca2+ in depolarised pancreatic
      islets.
AB  - Perifused rat pancreatic islets, prelabelled with 45Ca, were exposed for 90 min
      to a medium containing 30 mM K+, 0.25 mM diazoxide and 0.5 mM EGTA, but deprived
      of CaCl2. Either verapamil (0.05 mM) or Cd2+ (0.05 mM) were also present in the
      perifusate. Under these conditions a rise in D-glucose concentrations from either
      2.8 to 16.7 mM or zero to 8.3 mM increased both 45Ca outflow and insulin release,
      after an initial and transient decrease in effluent radioactivity. These findings
      suggest that, in islets depolarised by exposure to a high extracellular
      concentration of K+, D-glucose provokes an intracellular redistribution of Ca2+
      ions and subsequent stimulation of insulin release. The functional response to D
      glucose is apparently not attributable to either the closing of ATP-sensitive K+
      channels, which were actually activated by diazoxide, or stimulation of Ca2+
      influx, which was prevented by the absence of extracellular Ca2+. The present
      experimental design thus reveals a novel component of the glucose-induced
      remodelling of Ca2+ fluxes in islet cells. Such an effect might also be operative
      under physiological conditions, when the hexose leads to depolarisation of the
      islet B-cells.

PMID- 9638595
TI  - Lumbar collaterals of neurons of the C6 segment projecting to sacral segments of
      the cat spinal cord.
AB  - Electrophysiological investigations of neurons of the C6 segment of the spinal
      cord were made in alpha-chloralose anesthetized animals. It was established in
      the experiments that a part of long descending propriospinal neurons originating
      in the sixth cervical segment (C6) that projected to sacral segments (S1/S2) gave
      off collateral branches at the level of the fourth lumbar segment (L4). Several
      types of neurons were distinguished according to the ipsilateral, contralateral
      or bilateral course of axons at the thoracic level as well as their lumbar or
      sacral projections. The cell bodies of 58 identified neurons were distributed in
      Rexed's laminae VII and VIII of the gray matter. Axons descended in lateral
      funiculi and their conduction velocities varied from 50 to 85 m/s. The existence
      of collaterals to various segments of the lumbosacral enlargement indicates that
      the same information conveyed by long descending propriospinal neurons can reach
      separate motor centers controlling various muscles of the hindlimbs.

PMID- 9638596
TI  - Characteristic frequency bands of the cortico-frontal EEG during the sexual
      interaction of the male rat as a result of factorial analysis.
AB  - The electrocorticogram (ECoG) from the prefrontal cortex was simultaneously
      recorded with the accelerometric signals of pelvic thrusting performed by male
      rats during sexual behavior. The changes in the prefrontal ECoG were precisely
      correlated in time with well defined elements of male rat copulation. Principal
      component analysis allowed to identify three distinct bands of frequencies in the
      frontal ECoG: the absolute power (AP) of the 4-16 Hz band was increased in the
      500-ms periods before, during, and after the execution of pelvic thrusting in
      mount, intromission and ejaculation responses; the AP of the 18-24 Hz band was
      selectively increased during the execution of pelvic thrusting at the three
      copulatory responses, whereas the AP of the 26-32 Hz band was increased only
      during the pelvic moments of mount and intromission responses. These results show
      that the electroencephalographic activity of the prefrontal cortex of the male
      rat is related to the performance of sexual behavior, supporting the concept that
      this cortical area is involved in the organization of sequential behaviors, as
      sexual behavior.

PMID- 9638597
TI  - Deiodinase activity after short cold stimulation in rat.

PMID- 9638598
TI  - The free woman.

PMID- 9638599
TI  - Psychosomatic obstetrics and gynecology in the next millennium: some thoughts and
      observations.
AB  - While the importance of psychosocial and cultural issues inobstetric care has
      been increasingly acknowledged in recent decades there is still neglect and
      misunderstanding of what women want during pregnancy, birth and the postpartum
      period with regard to their care by health care providers. This paper highlights
      significant issues of concern which should be of value for caregivers, educators
      and health service planners as we move into the next millenium.

PMID- 9638600
TI  - A follow-up study of adolescent girls with early sexual debut in combination with
      gynecological problems.
AB  - This research examined the extent to which women's reproductive experiences
      during adolescence have repercussions in adult life with regard to sexuality,
      self-image and state of gynecological health. The investigated group comprised 30
      females (study group), with a sexual debut at the age of 15 years or younger and
      documented gynecological ill-health during adolescence. A comparison was made
      with 30 matched females from the same school classes (control group) without
      documented gynecological ill-health. At the age of 25-30 a semi-structured
      interview was conducted with both investigated and control participants. The
      majority of the women from the study group experienced their adolescent sexual
      experiences as generally negative. In early adulthood these women had more
      recurrent and varied gynecological illnesses than their control group
      counterparts. The study group women more often referred to their appearance as an
      indicator of their femininity than did the control women (who defined femininity
      in terms of 'to be in a relationship'). The study group women had a more negative
      attitude towards their own body than did the control women. Study group women's
      early sexual experience was also linked to an increase in norm-breaking behavior,
      lower educational attainment and a younger age of adult responsibilities compared
      with the control women.

PMID- 9638601
TI  - Psychometric aspects of the W-DEQ; a new questionnaire for the measurement of
      fear of childbirth.
AB  - Up to now it has been difficult to study fear of childbirth because of a shortage
      of adequate psychological measurements. Therefore the Wijma Delivery Expectancy/
      Experience Questionnaire (W-DEQ) was developed. This paper presents the
      theoretical background of the W-DEQ together with a documentation of the first
      psychometric studies. Examination of construct validity indicates that it seems
      to be possible to penetrate a psychological construct related to fear of
      childbirth by means of the W-DEQ, both before and after delivery, in nulliparous
      as well as in parous women. The questionnaire measures the construct more clearly
      in parous than in nulliparous women. Internal consistency reliability and split
      half reliability of the W-DEQ of > or = 0.87 are good for a new research
      instrument. More research is on its way to make the W-DEQ suitable even for
      measurements in applied settings.

PMID- 9638602
TI  - A comparative study of vertical and horizontal deliveries in the presence and
      with the assistance of the woman's partner.
AB  - The authors are the first in Hungary to have applied the method of vertical
      delivery with the husband's or partner's presence in the delivery room. This is
      part of the authors' family-centered delivery program at the Maternity Ward of
      Borsod-Abauj-Zemplen County Hospital, Miskolc. A comparison of 321 births was
      carried out, which included 158 vertical deliveries and 163 horizontal
      deliveries. During both vertical and horizontal deliveries, the husband or
      partner was present in the delivery room. The comparison included the mother's
      biometrics and social characteristics, as well as the circumstances of the
      delivery and the clinical parameters of the newborns. Certain stages of delivery
      in the vertical position took a shorter period of time compared to horizontal
      delivery, but the differences were not significant. Episiotomies were carried out
      in fewer cases of vertical deliveries, and significant injuries due to the lack
      of an episiotomy in the case of vertical deliveries were not detected. The
      parameters characterizing the clinical state of the newborns were the same in
      both groups. The answers given to questionnaires supported the favorable
      psychological effects of a vertical delivery. The authors hope that vertical
      delivery, as a possible alternative, will find its place in obstetric practice in
      Hungary.

PMID- 9638603
TI  - Puerperal and menstrual psychoses: the proposal of a unitary etiological
      hypothesis.
AB  - Puerperal and menstrual psychoses are both uncommon disorders and the occurrence
      of both in individual patients suggests the possibility of a common underlying
      pathogenesis. In this paper two cases are reported, the literature is reviewed
      and a unifying etiological hypothesis is postulated in which precipitous
      reductions in the brain estrogen environment precipitate episodes of psychosis in
      predisposed individuals. In the case of puerperal psychosis, estrogen cascade
      follows a lengthy period of sustained high brain estrogen environment; in
      menstrual psychosis, it is postulated that the occurrence in at least some cases
      of anovulatory menstrual cycles, wherein high levels of relatively unopposed
      estrogens are maintained until the next ovulatory cycle, play a role in priming
      the central nervous system prior to premenstrual estrogen cascade. Further
      research in this area using more sensitive techniques to follow hormonal
      fluctuation and mental state is called for.

PMID- 9638604
TI  - Assessment of menstrual regularity and irregularity using self-reports and
      objective criteria.
AB  - To assess subjective and objective definitions of menstrual regularity, and the
      relationship between them, 114 university students (mean age 20.3 years)
      prospectively recorded eight consecutive menstrual dates and reported whether
      they considered themselves 'regular' or 'irregular'. The percentage of women who
      reported being menstrually 'regular' or menstrually 'irregular' was compared with
      a classification developed according to a criterion based upon the results of
      their prospective menstrual records. According to self-reports and objective
      measures of regularity, a similar portion of the women (about 70%) were regular.
      But when cross-classifying regularity and non-regularity by the two procedures,
      it was found that only 44% of those who defined themselves as irregular were
      likewise defined by the objective criteria, whereas 82% of the women who defined
      themselves as regular were also deemed so by the objective criteria. It is
      concluded that some women will, and others will not, construe 'variability' as
      'irregularity'.

PMID- 9638605
TI  - Measured copper and zinc in body fluids.

PMID- 9638606
TI  - In vivo and in vitro effects of boron and boronated compounds.
AB  - Boron is ubiquitously present in soils and water. Associated with pectin it is
      essential for vascular plants as a component of cell walls, and it stabilizes
      cell membranes. It is required for the growth of pollen tubes and is involved in
      membrane transport, stimulating H(+)-pumping ATPase activity and K+ uptake.
      However, a high boron concentration in the soils is toxic to plants and some
      boronated derivatives are used as herbicides. An absolute requirement for boron
      has not been definitively demonstrated in animals and humans. However,
      experiments with boron supplementation or deprivation show that boron is involved
      in calcium and bone metabolism, and its effects are more marked when other
      nutrients (cholecalciferol, magnesium) are deficient. Boron supplementation
      increases the serum concentration of 17 beta-estradiol and testosterone but boron
      excess has toxic effects on reproductive function. Boron may be involved in
      cerebral function via its effects on the transport across membranes. It affects
      the synthesis of the extracellular matrix and is beneficial in wound healing.
      Usual dietary boron consumption in humans is 1-2 mg/day for adults. As boron has
      been shown to have biological activity, research into the chemistry of boronated
      compounds has increased. Boronated compounds have been shown to be potent anti
      osteoporotic, anti-inflammatory, hypolipemic, anti-coagulant and anti-neoplastic
      agents both in vitro and in vivo in animals.

PMID- 9638607
TI  - Distribution of selenium between plasma fractions in guinea pigs and humans with
      various intakes of dietary selenium.
AB  - The distribution of selenium between the plasma fractions was investigated in
      guinea pigs fed various levels (basal, 0.5, 1.0, 2.0, 4.0, 6.0 and 8.0 mg Se/kg)
      of dietary selenomethionine (Semet) and in humans living in different areas of
      China with different selenium status. There was a corresponding increase of
      selenium concentration in liver, kidney, brain, testis, spleen, heart and muscle
      with each increase of dietary selenium, but there were no increases of
      glutathione peroxidase (GPX) activity in liver, brain, testis, heart or muscle in
      pigs fed any of the selenium levels as compared to controls fed a basal
      commercial diet. On a percentage distribution basis, the selenium in
      selenoprotein P decreased and that in the albumin fraction increased with
      increased dietary intakes of selenium as Semet. The ratios of selenium to albumin
      in either the plasma or the albumin fractions increased with each increase in
      dietary selenium. The greatest percentage of selenium was in the albumin fraction
      of Chinese living in the high selenium areas whereas the greatest amount was in
      the selenoprotein P fraction in subjects living in deficient and adequate areas
      of China. Increases in the ratios of selenium to albumin in either the plasma or
      the albumin fraction also occurred with increases of selenium intake of these
      subjects. The results indicate that the distribution of selenium in plasma
      fractions reflect the levels of dietary intakes of Semet.

PMID- 9638608
TI  - An in vivo study of the gastrointestinal absorption site for zinc chloride in
      mice.
AB  - The experimental model presented below enables quantitation of the uptake of zinc
      (Zn++) into gastrointestinal mucosal cells in vivo using gamma-counting of 65Zn.
      Experiments were performed in mice fed their normal diet under natural
      physiological conditions. The in vivo site(s) of significant zinc absorption may
      thereby be identified. Absorption of zinc was extensive during the first hour
      after administration of a single oral dose of ZnCl2. Apparently, absorption
      continued during at least eight hours postdosage, and probably continued for 48
      hours. The intestinal mucosal labelling profile for zinc did not depend on dose
      size or the mode of administration (single oral doses or in drinking water). The
      duodenum and ileum were important sites for rapid zinc absorption. A continuous,
      slower absorption of zinc may take place in the jejunum. The stomach, caecum and
      colon appeared to be insignificant sites of zinc absorption. The transit time for
      zinc was very short as large quantities of zinc passed through the small
      intestine within one hour. In contrast to other studies, the intestinal labelling
      profile or the extent of zinc absorption were not changed in mice that received
      Tetraethylthiuram disulfide (TTD) in their food.

PMID- 9638609
TI  - Mercury in human colostrum and early breast milk. Its dependence on dental
      amalgam and other factors.
AB  - The mercury concentration in 70 breast milk samples (Hg-M) from 46 mothers,
      collected within the first 7 days after delivery, was determined by cold vapour
      atomic absorption spectrometry. For comparison, 9 formula milk samples
      (reconstituted with Hg-free water) were investigated. The Hg-M in the human milk
      samples ranged from < 0.2 to 6.86 micrograms/L (median 0.37), in the formula milk
      samples from 0.4 to 2.5 micrograms/L (median 0.76). The Hg-M in the breast milk
      samples correlates positively with the number of maternal teeth with dental
      amalgam. The mean Hg-M of amalgam-free mothers was < 0.2 microgram/L, while milk
      from mothers with 1-4 amalgam fillings contained 0.57 microgram/L, with 5-7
      fillings 0.50 microgram/L and with more than 7 fillings 2.11 micrograms/L. Hg-M
      correlated negatively to the day after delivery. Frequency of fish consumption
      tends to influence Hg-M positively, while the age of the mother shows no
      significant correlation. In the first 2 to 3 days after delivery some colostrum
      samples with Hg-M higher than in formula milk were found. Later on, the Hg
      concentration in the breast milk was equal or even lower to that in formula milk.
      The higher Hg burden of infants' tissues from mothers with dental amalgam, as
      reported previously, must be explained (1) by a prenatal transfer of Hg from the
      mother's fillings through the placenta to the fetus, followed by a redistribution
      of this Hg in the body of the newborn, and (2) an additional burden via breast
      milk. Nevertheless, the comparison of Hg-M in breast and formula milk, the
      relatively moderate Hg burden in both kinds of milk, and the multiple manifest
      advantages of breast feeding speak against any limitation of nursing, even for
      mothers with a large number of dental amalgam fillings.

PMID- 9638610
TI  - Trace elements and cardioprotection: increasing endogenous glutathione peroxidase
      activity by oral selenium supplementation in rats limits reperfusion-induced
      arrhythmias.
AB  - Oxyradicals have been implicated as a possible cause of reperfusion-arrhythmias
      (RA). However, the use of diverse exogenous oxyradical scavengers designed to
      reduce RA has given contradictory results. The aim of the present study was to
      determine whether enhancing the activity of the main endogenous enzyme involved
      in peroxide elimination in cardiac cells, namely glutathione peroxidase, may
      limit RA in isolated heart preparations by increasing their antioxidant status.
      For this purpose, a group of 15 male Wistar rats received a selenium enriched
      diet for ten weeks (1.5 mg Se/kg diet). Control animals (n = 15) received a
      standard diet containing 0.05 mg Se/kg diet. The incidence of early ventricular
      arrhythmias was investigated during the reperfusion period following 10 min
      regional ischemia induced ex-vivo by left coronary artery ligation. Our results
      show that selenium-supplementation significantly increased the global selenium
      status of the animals. In the isolated heart preparations, the selenium
      supplementation induced a significant reduction of the severity of RA as assessed
      by the arrhythmia score and the limitation of the incidence of both ventricular
      tachycardia (control: 91% vs selenium: 36%, p < 0.05) and irreversible
      ventricular fibrillation (control: 45% vs selenium: 0%, p < 0.05). These effects
      were associated with a significant increase in cardiac mitochondrial and
      cytosolic glutathione peroxidase activities in both the left and the right
      ventricles. These results illustrate the potential protective effect of selenium
      against ischemia-reperfusion injury and suggest that peroxides might play a key
      role in the genesis of some aspects of the reperfusion syndrome.

PMID- 9638611
TI  - Serum glycerol ester hydrolase activity is related to zinc and copper
      concentrations in atherosclerosis obliterans and aneurysm.
AB  - Although the body status of zinc and copper in cardiovascular disease (CVD) has
      been shown to be important little is known about the effect of these trace
      element alterations on lipolytic enzyme activities in atherosclerosis human
      subjects. The aim of the present study was to evaluate the multiple relationships
      between lipase (GEH = glycerol ester hydrolase, EC 3.1.1.3) activity, zinc,
      copper and lipid concentrations in serum and the arterial wall of men with
      atherosclerosis obliterans (AO) and abdominal aortic aneurysm (AA). The mean
      concentrations of zinc and copper in serum were found to be higher in AO in
      comparison to AA. Low but significant correlation coefficients for zinc and
      lipase catalytic activity (r > or = 0.64) and lipase metabolic activity GEH/TAG
      (r > or = 0.67) were calculated in serum in AA. Multiple correlation coefficients
      (R) for three variables GEH-Zn-Cu were found to be significant for both AO and AA
      (R > or = 0.45 and 0.68, respectively) in serum but not in the arterial wall.
      Multiple relations for GEH/TAG-HDL-C (LDLC)-Zn(Cu) were found to be significant
      (R > or = 0.63) in serum in AA. The results indicate the influence of zinc and
      copper on the activity of lipase and lipid concentrations and suggest that the
      multiple relations may provide a better understanding of the role these elements
      play in atherosclerosis than relations between 2 substances.

PMID- 9638612
TI  - Serum zinc and copper concentrations and Cu/Zn ratios in patients with
      hepatopathies or diabetes.
AB  - The serum zinc and copper levels, as well as Zn/Cu ratios, were determined in 30
      patients (18 with diabetes and 12 with hepatopathies) and compared to healthy-age
      matched controls by atomic absorption spectrometry. Serum Zn (0.946 +/- 0.302
      mg/l) and Cu (0.952 +/- 0.355 mg/l) concentrations were not significantly
      different in patients with hepatopathies as compared to controls (p > 0.05).
      Serum Zn concentrations (0.778 +/- 0.164 mg/l) were significantly lower in
      diabetic patients than those determined in controls (p < 0.01). In contrast, Cu
      levels (0.987 +/- 0.305 mg/l) were not significantly different (p > 0.05) than in
      controls. Serum Cu/Zn ratios were not significantly different in patients with
      diabetes or hepatopathies than those measured in healthy controls (p > 0.05). In
      patients, no statistically significant differences were observed in the Zn, Cu
      and Cu/Zn with respect to sex (p > 0.05) or age (p > 0.05).

PMID- 9638613
TI  - Adsorptive stripping measurements of iron accumulation in mice kidney using
      microelectrodes and histological features.
AB  - The toxic effects caused by iron in kidney was performed on experimental studies
      with mice following administration of a metallic solution of this species to
      simulate the iron corrosion products of a metallic implant. To quantify the total
      levels of iron present in this organ, an electrochemical method was chosen based
      on the application of square wave voltammetry using adsorptive collection of iron
      catechol on a mercury film microelectrode (MFM). The optimal working conditions
      to produce a very stable and reproducible iron peak in the digested kidney
      samples were found to be pH = 7.2 provided by 8.0 mmol/L PIPES buffer, catechol
      concentration of 3.0 x 10(-4) mol/L, deposition potential -1.80 V and deposition
      time 20 s. These results were compared with those obtained by atomic absorption
      spectrometry (AAS) indicating a good performance of the electrochemical method
      used. The analytical results show an increase of iron concentration with
      treatment time, which indicates that this metal ion is partially accumulated in
      the kidney. This accumulation induces with time some morphological alterations as
      evidenced by the histological analysis.

PMID- 9638614
TI  - On the interaction of the VO2+ cation with cystine.
AB  - The interaction between the VO2+ cation and cystine was investigated by electron
      absorption spectroscopy in aqueous solutions at different metal-to-ligand ratios.
      Reduction of NaVO3 solutions with cysteine gave similar spectra. The results
      suggest that interaction occurs through the carboxylate and amino groups of the
      ligand. The interest of the results in relation to vanadium metabolism are
      commented upon.

PMID- 9638615
TI  - Review of publications.

PMID- 9638616
TI  - The effects of melengestrol acetate on the ovaries of captive wild felids.
AB  - Melengestrol acetate (MGA) is the most widely used contraceptive in zoo felids,
      but the mechanism of contraception and the pathologic effects have not been
      investigated. For this study, the effects of MGA on folliculogenesis were
      assessed, and the association of MGA with ovarian lesions was evaluated.
      Comparisons were made among the histopathologic findings in the ovaries from 88
      captive wild felids (representing 15 species) divided into three groups: 37
      currently contracepted with MGA, eight previously exposed to MGA, and 43 never
      contracepted. Ninety-one percent of the felids evaluated had tertiary follicles,
      and no differences were noted between contracepted and uncontracepted cats. Some
      MGA-contracepted cats also had corpora lutea indicating recent ovulation. These
      results indicate that folliculogenesis not suppressed by current doses of MGA and
      ovulation occurred in some cats. Therefore, the contraceptive actions of MGA do
      not occur by suppressing folliculogenesis, and MGA-contracepted felids likely
      have endogenous estrogens that may confound progestin effects on the uterus.
      Cystic rete ovarii was the most common pathologic finding, but they were not more
      prevalent in MGA-contracepted cats. These findings indicate that MGA is not
      associated with ovarian disease, including ovarian cancer, in contrast to the
      uterine lesions noted in MGA-treated cats.

PMID- 9638617
TI  - Ultrasonographic evaluation of the effects of exogenous gonadotropins on
      follicular recruitment and ovulation induction in the Atlantic bottlenose dolphin
      (Tursiops truncatus).
AB  - Transabdominal ultrasonography and serum steroid concentrations were used to
      evaluate the effects of exogenous gonadotropin administration on ovarian activity
      of two anestrous bottlenose dolphins (Tursiops truncatus). The gonadotropin used
      for follicular recruitment was PG600, which has 400 IU equine chorionic
      gonadotropin (eCG) and 200 IU human chorionic gonadotropin (hCG) activity per 5
      ml. Ovulation induction was attempted with hCG. PG600 was administered in two
      doses of 20 ml (1,600 IU eCG and 800 IU hCG) and 12.5 ml (1,000 IU eCG and 500 IU
      hCG), respectively, 48 hr apart on days 0 and 2. On day 6, 1,500 IU of hCG was
      administered. Progesterone and total immunoreactive estrogens were determined
      before and after the gonadotropin administration. Bilateral ovarian
      ultrasonographic exams were performed daily on days 4-9 and on day 22. Serum
      immunoreactive estrogen concentrations were greater than the pretreatment
      concentrations after day 4 for both dolphins and remained elevated for the rest
      of the study. Serum progesterone concentrations rose above 1 ng/ml 2 days after
      hCG treatment and remained elevated for the rest of the study. Small antral
      follicles (< 0.5 cm) were initially observed bilaterally in both dolphins on day
      4. In both animals on day 9, there were > 12 follicles/ovary, ranging from 0.5 to
      1.5 cm. By day 22, the multiple follicles ranged from 0.5 to 4.5 cm in diameter.
      No ultrasonographic evidence of luteal formation was observed. The results
      indicate that 1) transabdominal ultrasonography can be used to detect and follow
      follicle growth in bottlenose dolphins; 2) bottlenose dolphins are sensitive to
      exogenous gonadotropins (multiple follicular recruitment of follicles occurred);
      and 3) until further ultrasonographic studies can be conducted to evaluate the
      effects of titrated doses of exogenous gonadotropins, these protocols should be
      considered unsuitable for ovulation induction.

PMID- 9638618
TI  - The effects of short-term physical restraint and isoflurane anesthesia on
      hematology and plasma biochemistry in the island flying fox (Pteropus
      hypomelanus).
AB  - The effects of short-term physical restraint and isoflurane anesthesia on
      hematologic and serum biochemistry parameters were evaluated in 12 island flying
      foxes (Pteropus hypomelanus). Physical restraint was associated with
      significantly decreased calcium, cholesterol, globulin, albumin, hemoglobin
      concentrations, red blood cell count, and hematocrit and increased glucose,
      phosphorus, and potassium concentrations. Isoflurane restraint was associated
      with significantly decreased calcium, cholesterol, albumin, globulin, and glucose
      concentrations, aspartate transaminase and alkaline phosphatase activities, white
      blood cell count, red blood cell count, hemoglobin, hematocrit, and total
      neutrophil and lymphocyte counts and significantly increased phosphorus and
      chloride concentrations. For those variables where both restraint forms produced
      an alteration (red blood cell count, hemoglobin, hematocrit, calcium, phosphorus,
      glucose), the magnitude of change was always significantly greater for the
      physically restrained animals. This study indicates that in adult flying foxes
      isoflurane anesthesia is preferable to physical restraint for collection of blood
      samples for hematologic and plasma biochemical analysis. Additionally, blood
      samples should be collected as soon as possible after capture, regardless of
      restraint technique.

PMID- 9638619
TI  - Serologic survey of free-living nestling prairie falcons (Falco mexicanus) for
      selected pathogens.
AB  - Serum samples from 34 free-living nestling prairie falcons (Falco mexicanus) in
      southwestern Idaho were negative for antibodies to avian influenza virus,
      Newcastle disease virus, and three Aspergillus species. Serum from a single bird
      had hemagglutinating inhibition activity in response to Mycoplasma synoviae, and
      another bird's serum had slight activity in response to M. gallisepticum.

PMID- 9638620
TI  - Use of monoclonal antibodies against chicken coccidia to study invasion and early
      development of Eimeria gruis in the Florida sandhill crane (Grus canadensis).
AB  - Eimeria gruis and E. reichenowi are common coccidial parasites of a number of
      crane species. In the present study, monoclonal antibodies (McAbs), elicited
      against Eimeria spp. of chickens and turkeys, cross-reacted with sporozoites and
      developmental stages of E. gruis in the tissues of Florida sandhill cranes. These
      McAbs were used to define the area of the intestine that was invaded by
      sporozoites of E. gruis and to demonstrate the feasibility of using McAbs to
      study the early development of E. gruis in the intestines and visceral organs of
      cranes. At 6 hr postinoculation (PI), E. gruis sporozoites were found primarily
      from just proximal to Meckle's diverticulum in the jejunum to the ileocecal
      juncture. Fewer sporozoites were found in the ceca and rectum, and none were
      found in the duodenum. Most of the sporozoites were in the middle third of the
      villi and within the lamina propria. At 14 days PI, developmental stages were
      detected in the ceca, jejunum, liver, and lungs but not in the heart, kidney, or
      brain. In the ceca and jejunum, the number, location, and maturity of the stages
      differed markedly.

PMID- 9638621
TI  - Trypanosoma cruzi infection of free-ranging lion-tailed macaques (Macaca silenus)
      and ring-tailed lemurs (Lemur catta) on St. Catherine's Island, Georgia, USA.
AB  - Free-ranging Old World primates released on St. Catherine's Island, Georgia
      (USA), were tested for infection with Trypanosoma cruzi as part of a study of the
      epizootiology of sylvatic T. cruzi in the southeastern USA. The parasite was
      observed in liver infusion tryptose medium cultures of blood from seven of 11
      lion-tailed macaques (Macaca silenus) and one of 19 ring-tailed lemurs (Lemur
      catta). Cultures of blood from 10 black and white ruffed lemurs (Varecia
      variegata) were all negative. Analysis of small subunit ribosomal RNA gene
      polymorphisms detected using polymerase chain reaction techniques indicates that
      the parasites isolated from both the lion-tailed macaques and the ring-tailed
      lemur are probably the same as T. cruzi parasites isolated from raccoons (Procyon
      lotor) trapped on St. Catherine's Island and other locations in the southeastern
      USA. Foraging lion-tailed macaques were observed to handle and partially consume
      specimens of Triatoma sanguisuga, the triatomine bug thought to be a vector of T.
      cruzi in the southeastern USA. Oral transmission of the parasite may have
      occurred as a result of this behavior.

PMID- 9638622
TI  - Recovery rates, serotypes, and antimicrobial susceptibility patterns of
      salmonellae isolated from cloacal swabs of wild Nile crocodiles (Crocodylus
      niloticus) in Zimbabwe.
AB  - Samples from the cloaca and the ventral skin surface of 67 Nile crocodiles
      (Crocodylus niloticus) captured in four uninhabited areas at Lake Kariba,
      Zimbabwe, were cultured for Salmonella. All the skin samples tested negative for
      Salmonella, whereas 18 of 67 (26.9%) cloacal samples grew Salmonella.
      Significantly more males than females yielded Salmonella, but no statistically
      significant correlation among salmonella carriage, body size, and age was
      recorded. Ten different serotypes of S. enterica belonging to the subspecies
      enterica, salamae, and diarizonae were isolated. All isolates belonging to
      subspecies enterica displayed invasive properties in an experimental mouse model
      and thus exhibited pathogenic potential, whereas none of the other isolates were
      invasive. In general, isolates were sensitive to a number of commonly used
      antimicrobials, except for three isolates that were resistant to streptomycin.

PMID- 9638623
TI  - Malignant seminoma with metastasis and herpesvirus infection in a free-living sea
      otter (Enhydra lutris).
AB  - In winter 1990, an adult male sea otter (Enhydra lutris) was found dead along the
      eastern shore of Prince William Sound, Alaska. Necropsy findings included an
      enlarged retained left testicle with a twisted spermatic cord, enlarged left
      sublumbar lymph node, emaciation, dental attrition, oral papules and ulcers, and
      luminal intestinal hemorrhage associated with numerous acanthocephalids. A
      malignant seminoma was present in the left testicle and left sublumbar lymph
      node. Additionally, herpesvirus like intranuclear inclusion bodies were found in
      oral, esophageal, and corneal epithelial cells. Virions consistent with a
      herpesvirus were found in esophageal epithelium. Dental attrition, severe
      intestinal acanthocephaliasis, the malignant seminoma, and emaciation were
      considered contributing factors in causing death. The herpesviral disease was
      probably secondary to the debilitation and stress. This is the first report of
      malignant seminoma with metastasis in a sea otter.

PMID- 9638624
TI  - Effects of lithium heparin and tripotassium EDTA on hematologic values of
      Hermann's tortoises (Testudo hermanni).
AB  - In an effort to define the effect(s) of lithium heparin and tripotassium EDTA on
      various hematologic parameters in Testudo hermanni, we collected blood samples
      from 29 clinically healthy adult individuals of both sexes. Portions of each
      blood sample were transferred to tubes containing either lithium heparin or
      tripotassium EDTA. The following determinations were made on samples of blood
      from each anticoagulant: red and white cell counts, packed cell volume,
      hemoglobin concentration, red cell indices, and differential white cell counts.
      Due to hemolysis, hematocrits could not be determined from blood samples in EDTA.
      Further, red blood cell counts were lower in the EDTA samples than in the heparin
      samples, again due to hemolysis associated with EDTA. However, EDTA did not
      appear to interfere with hemoglobin determinations. Heparin blood samples
      provided more optimal blood smears than did EDTA samples, thus differential
      leucocyte counts were determined only from smears taken from heparin blood
      samples. Further, thrombocyte and leucocyte aggregation was not observed with
      heparin use. Thus, heparin is considered the anticoagulant of choice in
      chelonians for determining red blood cell counts, erythrocyte indices, and
      hematocrits. When May-Grunwald-Giemsa stain was compared with Diff-Quick,
      thrombocytes could be more easily differentiated from lymphocytes using the May
      Brunwald-Giemsa stain. Heterophil granules seemed to coalese more when Diff-Quick
      was used. Eosinophils, basophils, and monocytes were similar in appearance with
      both staining methods.

PMID- 9638625
TI  - Chemical restraint of the Nile hippopotamus (Hippopotamus amphibius) in
      captivity.
AB  - This retrospective study describes 16 immobilizations performed on nine adult
      captive Nile hippopotamus (Hippopotamus amphibius). Animals were immobilized
      using intramuscular etorphine alone (1.0-5.0 micrograms/kg; n = 9) or in
      combination with xylazine (67-83 micrograms/kg; n = 6) or acepromazine (20
      micrograms/kg; n = 1). Exact weights for the animals were unknown so drug dosages
      were based on estimated weights. Seven animals either were in good health or had
      minor or localized medical problems. Following etorphine and xylazine induction,
      one animal undergoing castration was anesthetized with isoflurane in oxygen
      delivered by endotracheal tube. Ten immobilizations occurred without
      complications, and eight of those procedures were rated as good or excellent.
      Complications, including bradypnea, cyanosis, and apnea, occurred during six
      immobilizations. One animal died following prolonged apnea, and the necropsy
      failed to find a specific cause of death. Immobilizations were reversed with
      diprenorphine alone (4.4-10.0 micrograms/kg; n = 13), diprenorphine (2.9
      micrograms/kg) and naloxone (14.6 mu k/kg; n = 1), or naltrexone (146-180
      micrograms/kg; n = 2). Mean time to reversal of immobilization for those animals
      given etorphine alone and reversed with diprenorphine alone was 21.6 min (n = 5).
      Time to reversal for the two immobilizations reversed with only naltrexone was 4
      min. No renarcotizations were observed. Total doses of 2.0-6.0 mg etorphine i.m.
      should produce heavy sedation to surgical anesthesia in calm adult captive Nile
      hippopotamuses. Insufflation with oxygen during immobilization seems warranted.

PMID- 9638626
TI  - Presumptive dirofilariasis in a pale-headed saki monkey (Pithecia pithecia).
AB  - A 6-yr-old male pale-headed saki monkey (Pithecia pithecia), born at the Dallas
      Zoo, reentered the collection in 1994 after it was housed for 4 yr in Rhode
      Island and 2 yr in Florida. The monkey tested negative for both Dirofilaria
      immitis microfilariae and D. immitis adult antigens (via commercially available
      tests) upon return. However, it tested positive for adult antigens 1 yr later,
      and additional testing, including ultrasonography, suggested a diagnosis of
      aberrant dirofilariasis. Relevant evidence of previous microfilaremia in pale
      headed saki monkeys at the Dallas Zoo is reviewed. Dirofilaria immitis infection
      should be included in the differential diagnosis list for any nonhuman primate
      with cardiopulmonary disease wherever the parasite is enzootic.

PMID- 9638627
TI  - Fatal acute toxoplasmosis in three golden lion tamarins (Leontopithecus rosalia).
AB  - Fatal acute toxoplasmosis was diagnosed in three golden lion tamarins
      (Leontopithecus rosalia), a breeding pair and their male offspring, by histology
      and immunohistochemistry. The distribution and severity of lesions differed among
      the animals, but the small intestine and the pancreaticoduodenal lymph nodes were
      especially affected. Protozoal organisms consistent with Toxoplasma gondii
      tachyzoites, often clustered, were seen in all lesions and were specifically
      immunostained with a T. gondii polyclonal antibody. The infection was probably
      acquired orally. Several breeding groups of golden lion tamarins have succumbed
      to toxoplasmosis both in North American and European zoos, so this disease should
      be considered an important problem in this endangered species. Toxoplasma gondii
      can cause latent infections in New World primates and therefore could potentially
      induce abortions or congenital infections in wild golden lion tamarins born from
      latently infected reintroduced females.

PMID- 9638628
TI  - Isolation of a herpes simplex virus type 1-like agent from the brain of a
      mountain agile gibbon (Hylobates agilis agilis) with encephalitis.
AB  - A captive-born 2-yr-old male mountain agile gibbon (Hylobates agilis agilis) that
      died of encephalitis harbored a herpes simplex virus type 1 (HSV1)-like agent in
      the brain. A complete necropsy revealed intensive meningeal congestion with
      nonsuppurative encephalitis. The virus was recovered from frozen brain tissue in
      Vero cells. The isolate was very similar but not identical to human HSV1. Both
      western blot assay and virus neutralization tests were done with sera from 15
      gibbons. Antibodies against HSV1 and herpes simplex virus type 2 (HSV2) were
      detected in four healthy gibbons, which included four species in three subgenera.

PMID- 9638629
TI  - Agenesis of a radius in a polar bear cub (Ursus maritimus).
AB  - A polar bear (Ursus maritimus) cub, delivered by a cesarean section, was
      diagnosed with congenital agenesis of the radius on the basis of clinical
      presentation and radiology. A specific etiology could not be ascertained.
      Agenesis of the radius has not been previously reported in any nondomestic
      species.

PMID- 9638630
TI  - Granulomatous hepatitis associated with Hepatozoon sp. meronts in a southern
      water snake (Nerodia fasciata pictiventris).
AB  - A wild-caught adult female southern water snake (Nerodia fasciata pictiventris)
      did poorly in captivity. A peripheral blood-film examination demonstrated
      numerous hemogregarines characterized as fusiform nondividing intraerythrocytic
      gametocytes. Xenodiagnostic typing in laboratory-reared mosquitoes demonstrated
      the parasite to be of the genus Hepatozoon. Gross and histopathologic examination
      of the liver demonstrated numerous granulomas centered on groups of one to six
      Hepatozoon sp. meronts, an unusual finding in naturally infected wild-caught
      snakes.

PMID- 9638631
TI  - A fibrosarcoma in a Siamese crocodile (Crocodylus siamensis).
AB  - A fibrosarcoma of periosteal origin was identified in the oral cavity of a 22-yr
      old male captive Siamese crocodile (Crocodylus siamensis). The diagnosis was
      based upon the gross and light microscopical examination. The mesenchymal
      histogenesis was derived from the capability of the cells to produce collagen
      fibers. The invasive growth and the polymorphous cells in combination with the
      low mitotic index suggest a low-order malignancy. Attempts by immunohistochemical
      staining techniques to identify the specific lineage of the neoplastic cells and
      the expressed collagen type were unsuccessful.

PMID- 9638632
TI  - A fatal Pegosomum sp. (Trematoda: Echinostomatidae) infection in a wild cattle
      egret (Bubulcus ibis) from Japan.
AB  - An adult cattle egret (Bubulcus ibis) caught in Kobe of Hyogo Prefecture, Japan,
      in December 1995 died of a severe infection associated with the trematode
      parasite Pegosomum sp. At necropsy, 22 trematode parasites were found in the
      lumen of the bile duct, and the duct wall was markedly thickened.
      Histopathologically, severe cholangitis and cholecystitis were observed in close
      association with the parasites in the bile duct. Severe Pegosomum sp. infection
      may be one of the factors contributing to the mortality of wild cattle egrets.
      This is the first reported case of the genus Pegosomum infection in wild birds of
      Japan.

PMID- 9638633
TI  - Metastatic malignant mesothelioma in a tiger (Panthera tigris).
AB  - An 8-yr-old female tiger (Panthera tigris) died following a 2-wk history of
      progressive depression, anorexia, respiratory insufficiency, and exercise
      intolerance. At the time of necropsy, numerous coalescing, 4-20-mm, tan, firm
      nodules were scattered throughout the pleural surfaces of the thoracic wall and
      the mediastinum, giving a velvety appearance to these surfaces. Histologically,
      the nodules were diagnosed as malignant pleural mesothelioma. Secondary
      metastasis to the regional tracheobronchial and mediastinal lymph nodes was
      observed.

PMID- 9638634
TI  - Squamous cell carcinoma in an immature common stork (Ciconia ciconia).
AB  - An immature common stork (Ciconia ciconia) was referred from the Wildlife
      Recovering Center to the Department of Surgery for evaluation. Physical
      examination revealed a partially ulcerated, necrotic mass on the left surface of
      the upper beak. The mass was surgically removed and classified histologically as
      a squamous cell carcinoma. Postsurgically, the bird recovered uneventfully and
      proceeded to mature normally. During this growth period, no tumor recurrence or
      metastasis was detected, and no local bone alteration to the beak was found. The
      stork was ringed and released back into its natural environment.

PMID- 9638635
TI  - Clinical challenge. Internal hydrocephalus.

PMID- 9638636
TI  - Lung cancer: therapeutic modalities and cytoprotection.
AB  - Lung cancer is the leading cancer killer in the United States today. The current
      methods of treatment, radiation and various chemotherapies, have been used with
      some success; however, early detection remains the key to successful therapy.
      Current clinical trials indicate that an improvement of available therapies is
      needed. Consequently, the development of new approaches to treatment is foremost
      in the minds of researchers. Advances in molecular medicine have produced new
      drugs that can protect normal cells from chemotherapy-induced toxicities,
      resulting in enhanced drug delivery with few dose reductions. This review will
      discuss some of the advances that have been made in understanding the molecular
      biology of lung cancer as well as the current and most promising methods of
      treatment used for various forms of lung cancer. The potential contribution of
      cytoprotectors to enhance the safety and effectiveness of these therapies will be
      examined.

PMID- 9638637
TI  - Induction of manganese superoxide dismutase gene expression in bronchoepithelial
      cells after rockwool exposure.
AB  - Superoxide dismutases play an important protective role in the lung defense
      against the pro-oxidative effect of fibrous dusts (e.g. crocidolite fibers).
      Particularly crocidolite, but also other asbestos fibers, are known to induce
      cellular antioxidant defense. Although rockwool, a man-made fiber made from rock,
      is used widely for insulation purposes, its effects on the superoxide dismutases
      in bronchoepithelial cells have not been investigated. Thus, the purpose of this
      study was to determine whether human bronchoepithelial cells (BEAS 2B) respond to
      rockwool fibers (115-4 experimental rockwool fiber) by induction of MnSOD mRNA
      and an increase of MnSOD activity levels. The results were compared with BEAS 2B
      cells exposed to silica (alpha-quartz: DQ12; SiO2) and UICC (Union Internationale
      Contre le Cancer) crocidolite (concentrations of all dusts: 0, 2, 5, 10, 25, 50
      micrograms/cm2 = 0, 2.4, 6, 12, 30, 60 micrograms/ml; 24-h exposure) as control
      fibers. Scanning electron microscopy confirmed close dust cell contact under all
      experimental settings. Very low MnSOD mRNA baseline levels rose significantly (p
      < 0.001) in BEAS 2B cells exposed to all three dusts at 2 micrograms/cm2.
      However, at > 25 micrograms/cm2 MnSOD mRNA levels in silica- and crocidolite- but
      not in rockwool-exposed cells decreased. Slight (no significance) increases of
      MnSOD activity were observed which decreased at higher dust (> 5 micrograms/cm2)
      concentrations. These results suggest that: (1) like crocidolite and silica,
      rockwool accelerates MnSOD gene expression in bronchoepithelial cells; (2) an
      increase of MnSOD mRNA levels is not accompanied by MnSOD activity elevation; (3)
      in contrast to rockwool, high concentrations (> or = 25 micrograms/cm2) of
      crocidolite and silica reduced MnSOD activity and MnSOD mRNA levels. Because
      oxidants (H2O2) and crocidolite fibers were shown to reduce SOD activity, lack of
      active MnSOD protein may be caused by inactivation on a post-translational level.
      Furthermore, the decline of MnSOD mRNA and MnSOD activity levels coincides with
      increasing cytotoxicity. In conclusion, rockwool was demonstrated to induce MnSOD
      gene expression, perhaps because of its pro-oxidative effect in bronchoepithelial
      cells. In contrast to crocidolite and silica, rockwool fibers are not cytotoxic
      in this experimental setting.

PMID- 9638638
TI  - Effects of halothane, enflurane, isoflurane, and sevoflurane on slowly adapting
      pulmonary stretch receptor activity in anesthetized dogs.
AB  - The aim of this study was to evaluate the effects of halothane, enflurane,
      isoflurane, and sevoflurane on slowly adapting pulmonary stretch receptor (SAR)
      activity in dogs. Eight beagles were anesthetized with an intravenous injection
      of a mixture of urethane and alpha-chloralose as a basal anesthesia, then
      vagotomized, artificially ventilated, and chest opened. Single afferent
      activities from SARs were recorded from the peripheral nerve cut end of the left
      vagus. Changes in SAR activities with inhalation of halothane, enflurane,
      isoflurane, and sevoflurane at 1, 1.5, and 2 times the minimal alveolar
      anesthetic concentration (MAC) were measured, and differences in the discharges
      within and among four anesthetics were evaluated. As a result, two different
      types of SARs, low threshold SARs and high threshold SARs, were detected in this
      study. In all anesthetics, expiratory discharges of low threshold SARs decreased
      significantly in a dose-dependent manner, whereas inspiratory discharges did not
      change significantly at any anesthetic level. Discharges of high threshold SARs
      tended to decrease with increasing anesthetic level; however, no statistical
      significance was observed at any anesthetic level. Only one exception to these
      changes was observed at 1 MAC of halothane where no significant decrease in the
      expiratory discharge of low threshold SARs or significant increase in the
      discharge of high threshold SARs was induced against a control value. In
      conclusion, recent inhalation anesthetics, except for halothane at the light
      anesthetic level, tended to decrease SAR activities depending on the anesthetic
      level, suggesting attenuation of the Hering-Breuer inflation reflex.

PMID- 9638639
TI  - Changes in pulmonary mechanics after lung volume reduction surgery.
AB  - Lung volume reduction surgery (LVRS) is a promising new treatment for emphysema
      and leads to increased flow rates. We investigated the mechanisms by which flow
      rates could increase and the correlates of lessened dyspnea in patients
      undergoing LVRS before and 3 months after LVRS in patients with severe emphysema.
      The following were done: routine pulmonary function testing, measurements of
      elastic recoil (Pel), tidal breathing patterns, inspiratory work of breathing
      (Winsp), construction of static recoil-maximum flow curves, and measurement of
      baseline and transitional dyspnea index (TDI). There were increases in forced
      vital capacity (FVC: 2.24 +/- 0.71 to 2.92 +/- 0.63 liters; p < 0.05), forced
      expired volume in 1 (FEV1: 0.64 +/- .16 to 1.03 +/- 0.28 liters; p < 0.01), and
      decreases in all divisions of lung volume, e.g. total lung capacity (TLC: 6.86 +/
      1.41 to 5.96 +/- 1.49 liters; p < 0.01). Maximum Pel increased (11.7 +/- 3.7 to
      19.8 +/- 7.8 cmH2O; p < 0.02) as did the coefficient of retraction (CR = Pel/TLC:
      1.8 +/- 0.7 to 3.6 +/- 3.6 +/- 2.2 cmH2O/liter). However, the individual
      responses in other parameters were markedly different among patients. There was
      no consistent trend in changes in the slope or position of the static recoil
      maximum flow curve or Winsp. The only positive correlate of improved dyspnea (TDI
      = 3.22 +/- 2.22; p < 0.01) was improvement in CR, FEV1 being a weak negative
      correlate and change in lung volume not being a correlate at all. We conclude
      that there is a heterogeneous response of the airways to LVRS. Increased elastic
      recoil was the primary determinant of improved flow rates after LVRS and is the
      only positive correlate for improvement in dyspnea.

PMID- 9638640
TI  - Isoniazid levels in the bronchoalveolar lavage fluid of patients with pulmonary
      tuberculosis.
AB  - Isoniazid (INH) is one of the most important first line drugs in the treatment of
      tuberculosis. We utilized high performance liquid chromatography with a hydrazone
      extraction technique to measure INH in bronchoalveolar lavage (BAL) fluid
      specimens from six patients with active pulmonary tuberculosis. We found BAL
      fluid INH levels to be similar to 2-h peak serum levels. The concentration of INH
      in BAL fluid from lobes with infiltrate was similar to the concentration of INH
      in BAL fluid from lobes without infiltrate (0.062 microgram/ml and 0.073
      microgram/ml, respectively). After adjusting for protein concentration in the BAL
      fluid, INH levels in lobes with infiltrate were threefold lower than in lobes
      without infiltrate. The correlation between the concentration of INH in serum and
      BAL fluid approached significance after correcting for protein (lobes with
      infiltrate, r2 = 0.60 (p = 0.07); lobes without infiltrate, r2 = 0.50 (p = 0.12).
      INH penetrates into bronchoalveolar fluid, and concentrations of INH in the BAL
      fluid suggest that assessment of the INH serum concentration is adequate to
      evaluate bioavailability of the drug in patients with pulmonary tuberculosis.

PMID- 9638641
TI  - Experimental hypersensitivity pneumonitis: location of transferring cells.
AB  - Cultured cells from Micropolyspora faeni-sensitized donors can adoptively
      transfer murine experimental hypersensitivity pneumonitis (EHP). We sought to
      determine the location of transferred cells in recipient animals, the influence
      of the origin of the cultured cells, and the effect of specific intratracheal
      challenge. We labeled cultured sensitized spleen or lung-associated lymph node
      (LALN) cells with CFDA-SE, a cytoplasmic stain, before transfer to naive
      recipients, which were sacrificed 1 h, 1 day, or 4 days thereafter. We also
      transferred labeled cultured spleen cells to recipients that were challenged with
      intratracheal M. faeni and sacrificed 4 days later (MF). Controls were recipients
      of M. faeni-sensitized and cultured cells challenged with intratracheal normal
      saline (NS) and recipients of ovalbumin (OVA)-sensitized cells cultured with M.
      faeni and challenged with intratracheal M. faeni (OVA). The number and proportion
      of cells that were stained were determined in dispersed spleen, peripheral and
      lung-associated lymph nodes, and lung parenchyma. The extent of the pulmonary
      inflammatory response was measured by determining the proportion of microscopic
      fields that were abnormal and the total number of dispersed pulmonary cells. CFDA
      SE stained cells uniformly, and stained cells could be detected in recipients for
      up to 7 days after transfer. CFDA-SE treatment (0.5 microM) did not affect the
      ability of cells to transfer EHP adoptively. Transferred cells could be detected
      easily in lung, lung-associated and peripheral lymph nodes, blood, and spleen.
      Transferred cells localized to the lung at 1 h but then rapidly decreased with no
      difference between labeled cells from spleen and LALN. After intratracheal M.
      faeni challenge, there was no difference in the proportion of labeled cells in
      the lung among any of the groups (MF, NS, or OVA). There was an increase in the
      number of lung cells in the MF group compared with the control (NS and OVA)
      groups. We conclude that cells capable of transfer are transiently (1 h) trapped
      in the lung but are much decreased in the lung by four days after transfer. After
      intratracheal antigen challenge of recipients, there is a substantial increase in
      the number of pulmonary cells in animals exhibiting adoptive EHP but not in the
      control groups. Transferred cells responsible for EHP are increased in the lungs
      of animals with adoptive EHP.

PMID- 9638642
TI  - Cloning and characterization of a tobacco cDNA encoding calcium/calmodulin
      dependent glutamate decarboxylase.
AB  - In plants, gamma-aminobutyric acid (GABA), a major transmitter in the central
      nervous system in animals, is synthesized by glutamate decarboxylase (GAD), the
      activity of which is tightly modulated by Ca2+/calmodulin. To study the molecular
      mechanism of GAD regulation and examine the physiological role of GABA in plants,
      we isolated and characterized a 1771 bp tobacco cDNA clone, pNtGAD2. The 496
      amino acid sequence deduced from pNtGAD2 showed 97, 92, and 81% identity to
      NtGAD1, petunia, and tomato GAD, respectively. The 26 amino acid sequence within
      the putative calmodulin binding domain at the carboxy terminus showed a typical
      alpha-helical structure with hydrophobic and charged amino acid clusters. The
      pNtGAD2-encoded 56 kDa protein interacted strongly with a monoclonal antibody
      against the petunia GAD and its GAD activity was stimulated markedly by the
      addition of exogenous calcium and calmodulin. The molecular sequence of pNtGAD2
      and biochemical characteristics of the pNtGAD2-encoded protein confirmed that
      pNtGAD2 is a clone encoding a functional calmodulin-binding and Ca2+/calmodulin
      dependent tobacco glutamate decarboxylase. This result indicates that tobacco
      plants also have Ca2+/calmodulin-dependent GADs.

PMID- 9638643
TI  - Saccharomyces cerevisiae STE11 may contribute to the stabilities of a scaffold
      protein, STE5, in the pheromone signaling pathway.
AB  - Saccharomyces cerevisiae STE5 is an essential component of the pheromone-mediated
      mitogen activated protein kinase (MAPK) pathway. The STE5 protein recruits MAPK
      module kinases (STE11, STE7, and FUS3) to give a specificity for the pheromone
      pathway. The STE5 protein contains a putative PEST motif for ubiquitin-dependent
      protein degradation, and its level may be important for regulation of pheromone
      signal transduction. In this article, we studied the roles of proteins associated
      with the STE5 protein for its stabilization by analyzing ste deletion mutants.
      Here, we found that the STE11 kinase performed the most important role in
      stabilization of the STE5 protein. The level of STE5 protein was significantly
      low in the absence of STE11 kinase, suggesting essential roles of STE11 in
      stabilization of the STE5 protein. Immunodetection and Northern blot analyses
      showed that the low level of the STE5 protein in the ste11 delta mutant is not
      due to the level of gene expression but to that of protein stability. Measurement
      of relative binding affinities showed that the STE11 protein tightly interacts
      with the STE5 protein for its stabilization.

PMID- 9638644
TI  - Spinach cytosolic fructose-1,6-bisphosphatase: I. Its organ-specific and
      developmental expression characteristics.
AB  - Spinach (Spinacia oleracea) cytosolic fructose-1,6-bisphosphatase (FBPase) was
      purified and the final preparation of protein has a specific activity of about 45
      units/mg protein and a single band of molecular mass of 39 kDa. Polyclonal
      antibody against the protein did not cross-react with chloroplast FBPase, but
      showed strong cross-reactivity with all plant cytosolic FBPases tested. Studies
      of the FBPase expression characteristics at early stages of development
      demonstrated that it was controlled at both the transcriptional and translational
      levels, and its mRNA was detected even in etiolated cotyledons. This suggests
      that the expression is not light-inducible. A single transcript was detected in
      all spinach tissues tested. Western blot analysis revealed two protein bands in
      the etiolated cotyledons: one was the same size as that present in the mature
      leaf, and the other slightly smaller. A high enzyme activity was detected in
      etiolated cotyledons, especially compared to protein levels in Western blots.
      Expression of the cytosolic FBPase gene during leaf development showed no change
      in the steady-state level of mRNA, but the protein level and enzyme activity were
      higher in mature leaves than in young ones, suggesting that the increase in
      FBPase activity during development is due to an increase in protein synthesis.
      Young roots showed low enzyme activity, but an unexpectedly high activity was
      detected in old fiber roots.

PMID- 9638645
TI  - Spinach cytosolic fructose-1,6-bisphosphatase: II. Light effect on its
      expression.
AB  - The effect of light on the expression of spinach (Spinacia oleracea) cytosolic
      fructose-1,6-bisphosphatase (FBPase) was determined by the level of mRNA, protein
      content, and enzyme activity. It was found that its expression and activity were
      constant and stable during normal daily conditions as well as under continuous
      light or dark conditions. However, two different mRNAs were detected; one
      transcript was expressed all the time, while the other was detected only during
      prolonged dark periods. Analysis of the expression of the mRNAs at the protein
      level using an activity gel showed that this "darkness-specific" mRNA encoded a
      separate, distinct polypeptide. Thus, our data suggest that cytosolic FBPase is
      encoded by a small multigene family.

PMID- 9638646
TI  - Top DNA polymerase from Thermus thermophilus HB27: gene cloning, sequence
      determination, and physicochemical properties.
AB  - A gene, top encoding Thermus thermophilus HB27 (Top) DNA polymerase, was cloned
      in E. coli and its nucleotide sequence was determined. Based on its deduced amino
      acid sequence, Top DNA polymerase is a 93.8 kDa protein comprising 834 amino acid
      residues. Top DNA polymerase showed high amino acid homology with those of other
      DNA polymerases from the Thermus sp., for example, 87.3% identity with Taq DNA
      polymerase. Codon usage in the top gene was similar to those of the proteins from
      other Thermus strains. The G + C content in the third position of the codons was
      as high as 93%. The top gene under the control of the tac promoter was expressed
      in E. coli [plasmid pTOP9]. DNA amplification using the recombinant Top DNA
      polymerase performed the same as other thermostable DNA polymerases from Thermus
      strains. The optimum temperature for its reaction was 76 degrees C. An
      interesting observation was that the recombinant Top DNA polymerase was slowly
      cleaved into two fragments of about 60 kDa and 35 kDa at 4 degrees C and -20
      degrees C. The larger fragment possessed polymerase activity like the Klenow
      fragment of E. coli DNA polymerase I. To prevent the cleavage of the Top DNA
      polymerase, a variety of protecting agents were examined. Among those examined,
      (NH4)2SO4 (100 mM) solution demonstrated an outstanding ability to block its
      cleavage for a prolonged period.

PMID- 9638647
TI  - Characterization of Mas-7-induced pore formation in SK-N-BE(2)C human
      neuroblastoma cells.
AB  - Mastoparan, a peptide toxin from wasp venome, mimics receptors by stimulating the
      GTPase activity of guanine nucleotide binding proteins and the G-protein-coupled
      phospholipase C (PLC). By using Mas-7, the active analog of mastoparan, we showed
      that it makes pores in the plasma membrane. Treatment with Mas-7 but not Mas-17,
      the inactive analog, produced a concentration-dependent rise in intracellular
      Ca2+ concentration ([Ca2+]i) and facilitated the uptake of ethidium bromide
      (EtBr) (314 Da) to a sustained level during the stimulation. In addition, Mas-7
      triggered the influx of lucifer yellow (457 Da), while it did not induce the
      influx of fura-2 (831 Da) and Evans blue (961 Da). However, the Mas-7-induced
      permeability was selectively prevented by the addition of La3+, Ni2+, and Co2+,
      but not Cd2+. This blocking activity was concentration-dependent. While the
      stimulatory effect of Mas-7 on PLC activity was dependent on extracellular Ca2+,
      the pore forming activity of Mas-7 was not effected by removal of extracellular
      Ca2+. These results, therefore, suggest that the mastoparan's action in pore
      formation is independent from its action in PLC stimulation and is negatively
      effected by inorganic cations.

PMID- 9638648
TI  - Development of a new anti-CD4 monoclonal antibody (YG23) which inhibits the
      formation of colonies of human bone marrow progenitor cells.
AB  - We have previously reported CD4 expression in CD34+ hematopoietic progenitor
      cells and suggested a role of CD4 in normal hematopoiesis and its possible
      relationship with the pathogenesis of acquired immunodeficiency syndrome (AIDS).
      To investigate whether CD4 expression in bone marrow progenitor cells can explain
      bone marrow suppression in AIDS, monoclonal antibodies (mAbs) against human CD4
      were developed by immunizing Balb/c mice with human thymocytes. Three mAbs
      completely blocked the binding of Leu3a antibody, a well-known anti-CD4 mAb, to
      thymocytes, which indicates overlap between the epitopes recognized by these and
      Leu3a antibodies. Interestingly, one of these mAbs, YG23, significantly inhibited
      colony formation of human bone marrow progenitor cells treated with GM-CSF. This
      is the first demonstration that ligation of CD4 by an anti-CD4 mAb suppresses GM
      CSF mediated proliferation and differentiation of human hematopoietic progenitor
      cells by modifying the intracellular signaling pathway through CD4 molecules.
      Based on these findings, we propose that alteration of CD4 signaling by either
      cross-linked gp120 or antibodies directed against a certain epitope shared with
      the YG23 binding site of the CD4 molecule may play a role in bone marrow
      dysfunction in AIDS patients.

PMID- 9638649
TI  - Sequencing and chromosomal localization of the RA138 gene encoding a rice
      allergenic protein.
AB  - A cDNA clone (RA138) encoding a rice allergenic (RA) protein has been isolated
      during a large-scale random sequencing of a cDNA library prepared from developing
      seeds. The nucleotide sequence of the RA138 gene contained an open reading frame
      (ORF, 477 bp) encoding a 17 kDa protein. The amino acid sequence deduced from the
      ORF was composed of 159 amino acid residues and was highly homologous to those
      from RA genes previously isolated, such as RA5 (92% identity), RA14 (73%), and
      RA17 (68%). The protein contained 10 cysteine residues that were conserved in the
      alpha-amylase/trypsin inhibitor family including RA proteins. Excluding a
      putative signal peptide consisting of 26 amino acid residues, the mature protein
      would be 14.4 kDa in size and have a pI of 7.0. DNA gel blot analysis under high
      stringency conditions indicated that multiple copies of the RA138 gene were
      present in the rice genome. The chromosomal location of the RA138 gene has been
      identified on chromosome 7 in a segregation analysis using a population of 164
      recombinant inbred lines derived from a cross between Milyang 23 and Gihobyeo.
      The locus that may contain multiple copies of the RA138 was located between RFLP
      markers RG477A and C492 with genetic distances of 10.7 cM and 6.7 cM,
      respectively.

PMID- 9638650
TI  - Genome characterization of a Korean isolate of cymbidium mosaic virus.
AB  - The complete nucleotide sequence of the genomic RNA of a Korean isolate of
      cymbidium mosaic virus (CymMV-K2) was determined. The genomic RNA is 6227
      nucleotides in length, excluding the poly(A) tail. It contains a 5'-noncoding
      region (NCR) of 73 nucleotides, five open reading frames (ORFs 1 to 5) which
      encode proteins with M(r) 160 kDa RNA-dependent RNA polymerase (ORF1), 26 kDa
      movement protein 1 (ORF2), 13 kDa movement protein 2 (ORF3), 10 kDa movement
      protein 3 (ORF4), 24 kDa coat protein (OFR5), and a 3' NCR of 76 nucleotides. The
      5'-end of the CymMV-K2 genome initiates with GGAAAA which contrasts to GAAAA at
      the 5'-ends of other potexviruses, including a Singapore isolate of CymMV (CymMV
      S2). When compared with CymMV-S2, 171 base substitutions were observed in the
      CymMV-K2 genome. Substitutions in the overlapping ORFs (ORFs 2 to 4) occurred
      more frequently than those in 5' NCR, ORF1, and 3' NCR. In addition to
      substitutions, two single-base deletions, one in the intercistronic region
      between ORF1 and ORF2 and the other in the ORF2, were found on the CymMV-K2
      genome. The deletion in the ORF2 induced a frameshift which altered the C
      terminal domain of movement protein 1. ORF3 and ORF4 of the CymMV-K2 genome are
      partially different from those of another Singapore CymMV genome (CymMV-S1) which
      has four frameshifts due to nucleotide deletions within these ORFs.
      Interestingly, the frameshifts resulted in no change in the conserved sequences
      of the movement proteins but reconstructed their transmembrane domains.

PMID- 9638651
TI  - High level accumulation of an aberrantly spliced human DHFR RNA species.
AB  - Cells transduced with either of two human DHFR minigenes express an RNA product
      which is considerably shorter than what would be predicted from the size of an
      unspliced transcript expressed from its DNA template. RNA blotting analysis has
      shown that this short transcript accumulated to exceedingly high levels which
      were comparable to the levels reached by the highly abundant endogenous actin
      mRNA, or MoMLV RNA expressed in chronically infected cells. RNA blotting, RNase
      mapping, primer extension, RT-PCR, and sequencing have shown that this highly
      expressed transcript, termed TBN, is a spliced RNA product which utilizes cryptic
      splice signals present in the normally spliced DHFR mRNA. Subcloning experiments
      have demonstrated that all the information required for the generation and high
      level accumulation of the TBN transcripts is encoded in the 1.6 kb DHFR DNA
      minigene. TBN transcripts were generated with comparable efficiency from DNA
      templates containing either the human ADA or the early SV40 promoters. Since
      neither the ADA nor the SV40 promoter are considered to be particularly "strong"
      promoters, this observation argues that initiation of transcription is not the
      rate limiting step in determining the amount of the TBN transcripts which
      accumulate in the cell. Insertion of a foreign sequence into the DHFR DNA
      minigene led to the expression and high level accumulation of a chimeric
      transcript, suggesting that the unusual properties of this expression system may
      be used for high level expression of foreign sequences. These observations offer
      new insights into the mechanisms which control the accumulation of translatable
      mRNA in the cell, and have potentially important implications for experiments
      involving optimization of gene expression for gene therapy applications.

PMID- 9638652
TI  - Increased expression of the gentamicin resistance gene by a Tn3 sequence located
      at the upstream region.
AB  - Recombinant plasmids designated as pCH1 and pCH21 were constructed to determine
      the influence of the bla sequence on the expression of the gentamicin resistance
      gene which is located downstream of Tn3. Minimal inhibitory concentration (MIC)
      test and Northern hybridization results with the constructed plasmids showed that
      the transcription of the gentamicin resistance gene was initiated from the
      promoter, located downstream from the PstI site within the bla gene, and the
      hybrid promoter created by IR sequences of Tn3. Although the read-through
      transcription from the bla promoter did not occur, the transcription of the bla
      gene increased the expression of the gentamicin resistance gene.

PMID- 9638653
TI  - Effects of dopamine and estrogen on the regulation of Pit-1 alpha, Pit-1 beta,
      and PL-II gene expression in the rat placenta.
AB  - Pituitary-specific transcription factor Pit-1 regulates growth hormone and
      prolactin gene expression in the pituitary. Recently, Pit-1 was shown to be
      locally synthesized in the rat placenta and is involved in the regulation of rat
      placental lactogen (PL) gene expression. Pit-1 has three different splicing
      variants. They are well known as being biologically active. In the present study,
      we found that Pit-1 beta is also synthesized in the rat placenta and we tried to
      examine the effects of dopamine and estrogen on the regulation of Pit-1 alpha,
      beta and PL-II genes expression using the reverse transcription-polymerase chain
      reaction (RT-PCR) and Northern blot hybridization. A dopamine receptor agonist,
      bromocriptine, significantly decreased placental Pit-1 alpha, beta, and PL-II
      mRNA levels. To examine the effect of estrogen on the gene expression of Pit-1
      beta, pregnant female rats were ovariectomized (OVX) and injected daily with 17
      beta-estradiol. OVX markedly lowered the amount of Pit-1 beta mRNA. Estrogen
      injection recovered the OVX-induced inhibition of Pit-1 beta mRNA level. Finally,
      we investigated the site-specific transcription of Pit-1 alpha and beta mRNA in
      the labyrinth zone and junctional zone of the placental in 15 and 20 days of
      gestation. The main site of Pit-1 alpha and beta synthesis was shifted from the
      junctional zone to the labyrinth zone from 15 to 20 days of gestation. Together,
      these data presume that Pit-1 beta may play a more important role in the placenta
      than in the pituitary and that Pit-1 may be involved in the regulation of the PL
      and prolactin-like peptide by estrogen and dopamine in the rat placenta.

PMID- 9638654
TI  - Identification of differentially expressed genes in human hepatoblastoma cell
      line (HepG2) and HBV-X transfected hepatoblastoma cell line (HepG2-4x).
AB  - Hepatitis B virus-X protein (HBV-X) is known to be an important factor in the
      formation of hepatocellular carcinoma by acting as a transcriptional activator on
      viral or cellular genes. To identify differentially expressed genes between the
      human hepatoblastoma cell line HepG2 and HBV-X gene transfected hepatoblastoma
      cell line HepG2-4X, we used a differential display polymerase chain reaction
      technique. The technique produced numerous up-regulated and down-regulated bands,
      each representing a partial cDNA fragment. We isolated 23 different kinds of cDNA
      fragments that showed marked differences in two cell lines. The fragments were
      used as templates for DNA sequencing analysis and as probes for Northern blot
      analysis. This analysis revealed that eight cDNA clones were differentially
      expressed in each cell line but fifteen cDNA clones were not. Among the 8 clones,
      3 clones showed sequence similarities with human mitochondrial ATPase subunit 6
      (mtATPase 6) and the human amidophosphoribosyl transferase (ATase) precursor,
      whereas 5 other clones were human novel protein encoding genes. Two genes having
      similarity with known genes were repressed by HBV-X. These results reflect that
      complex alterations of the expression of enzymes concerning the energy-generating
      system in mitochondria and metabolite synthesis are closely associated with the
      HBV-X function during the formation of hepatocellular carcinoma. These newly
      obtained genes will be useful for analyzing HBV-X functions. We are in the
      process of further characterizing these genes.

PMID- 9638655
TI  - Sequence analysis and expression of Met-rich storage protein SP-1 of Hyphantria
      cunea.
AB  - We isolated and sequenced a cDNA clone corresponding to the 2.5 kb storage
      protein (SP-1) from fall webworm, Hyphantria cunea. The SP-1 gene encoded a pre
      protein of 753 amino acids, including a signal peptide of 15 amino acids. The
      deduced amino acid sequence of SP-1 contained one potential N-glycosylation site,
      and the calculated isoelectric point and molecular weight of secreted SP-1 were
      pI = 8.38 and 86.8 kDa, respectively. A Northern blot of mRNA from various
      developmental stages revealed that the SP-1 mRNA in fat body appears in early
      last instar larvae and accumulates to a maximum level at the end of last instar
      larvae. The persistence of SP-1 transcript through the early pupal stage suggests
      that its mRNA might be stable or expressed during the pupal stage. SP-1
      transcription was also found in the ovary as well as testis. This local
      expression of SP-1 in both reproductive organs seems to allow the insect to keep
      its reproductive activity under a nutritional stress.

PMID- 9638656
TI  - Sequence variation of EBNA2 of Epstein-Barr virus isolates from Korea.
AB  - To reveal sequence variations in the Epstein-Barr virus nuclear antigen 2 (EBNA2)
      genes of Epstein-Barr virus (EBV) strains circulating in the Korean population,
      the EBNA2 divergent region was amplified and sequenced from 13 EBV-1 isolates, 2
      EBNA2 type 1 intertypic EBV isolates, and two EBV-2 isolates, all derived from
      Korean cancer patients. Comparative sequence analysis revealed that type 1 and
      type 2 EBNA2 divergent regions of Korean EBV isolates were almost identical to
      the respective regions of the B95-8 EBV-1 and AG876 EBV-2 strains. Two of the
      nucleotide changes found in the type 1 divergent regions of all Korean isolates,
      G-to-T and C-to-A at B95-8 EBV positions 48,991 and 48,998, respectively, are
      also present in all EBV-1 strains of non-Asian origins, indicating that these two
      sites might be mutational hot sites. Besides these two mutations, EBV-1 strains
      from Papua New Guinea or European Caucasians and Africa show unique patterns of
      identical sequence variations from B95-8, which were not found in type 1 isolates
      from Korea, suggesting that Korean type 1 are evolving as a lineage distinct from
      isolates from Papua New Guinea or European Caucasian and Africa.

PMID- 9638657
TI  - Cholesterol biosynthesis from lanosterol: differential inhibition of sterol delta
      8-isomerase and other lanosterol-converting enzymes by tamoxifen.
AB  - The fact that administration of tamoxifen (Tam) to humans and laboratory animals
      (e.g., rats and monkeys) results in both a drastic reduction in cholesterol and a
      marked accumulation of certain sterol intermediates in their serum led us to
      undertake more direct biochemical studies on the mechanism of Tam's inhibitory
      action on the cholesterogenic enzymes. Of the five rat hepatic lanosterol
      converting enzymes examined, the enzyme most sensitive to inhibition by Tam was
      sterol delta 8-isomerase (delta 8-SI) (a 208-fold inhibition relative to
      lanosterol 14 alpha-methyl demethylase), followed by sterol delta 24-reductase
      (13-fold) and sterol delta 14-reductase (5.2-fold). The inhibition patterns of
      all four affected enzymes were found to be noncompetitive, despite widely
      different inhibition constants (Ki) of 0.21 to 23.5 microM. The inhibitory
      activity of Tam on delta 8-SI was not affected by detergent-mediated
      solubilization of the microsomes. In Chinese hamster ovary cells, inhibition of
      delta 8-SI activity (IC50 = 0.15 microM) was paralleled by a decreased rate of
      [14C]-mevalonate incorporation into cholesterol (IC50 = 0.70 microM). Our results
      should provide more insight into an underlying mechanism of Tam's
      cardioprotective role by interfering the operation of the pathway of cholesterol
      biosynthesis from lanosterol in mammals.

PMID- 9638658
TI  - Byr4, a dosage-dependent regulator of cytokinesis in S. pombe, interacts with a
      possible small GTPase pathway including Spg1 and Cdc16.
AB  - Coordination between karyokinesis and cytokinesis in the cell division cycle is
      fundamental to a precise transmission of duplicated genome into dividing daughter
      cells. byr4, a previously isolated essential gene, affects the mitotic cell cycle
      and cytokinesis in S. pombe. Phenotypic analyses of the null alleles and the
      overexpression of byr4 suggest that byr4 is a dosage-dependent coordinator of
      karyokinesis and cytokinesis (Song et al., 1996). In this study, the functional
      mechanisms of byr4 were investigated using a byr4 mutant that exhibits byr4
      overexpression phenotypes in thiamine deficient media. Genetic suppression
      analyses of this byr4 mutant with other cytokinesis regulatory genes in S. pombe,
      cdc16, cdc7, cdc15, cdc14, and plo1, show that byr4 overexpression phenotypes are
      suppressed by the overexpression of cdc16 and cdc7, but not by plo1, cdc14, and
      cdc15. Also, the basal expression of byr4 and cdc7 suppresses the temperature
      sensitive cdc16 mutation. However, the basal expression of either byr4 or cdc16
      does not suppress the temperature-sensitive cdc7 mutation. The results of these
      suppression tests suggest that byr4 genetically interacts with cdc16 and cdc7:
      byr4 functions at the same level with or downstream of cdc16 and upstream of
      cdc7. In the present study, we also show that Byr4 interacts with Cdc16 and Spg1
      in the yeast two-hybrid assays. Recent reports suggest a possible small GTPase
      pathway to regulate the timing of cytokinesis where Cdc16 functions as a GAP
      (GTPase activating protein), Spg1 as a GTPase, and Cdc7 as a downstream effector.
      Combined genetic and two-hybrid analyses of this study strongly suggest that Byr4
      directly interacts with this possible small GTPase pathway including Cdc16, Spg1,
      and Cdc7 to regulate cytokinesis in S. pombe.

PMID- 9638659
TI  - Analysis of TNFB and TNFA NcoI RFLP in colorectal cancer.
AB  - We examined the relationship between the NcoI RFLP of tumor necrosis factor beta
      (TNFB) and alpha (TNFA) genes and the risk of colorectal cancer. The first intron
      of TNFB and the -308 promoter region of TNFA NcoI RFLP were ascertained from
      peripheral leucocytes of 136 colorectal cancer patients and 325 healthy controls.
      The TNFB*1/TNFB*1 homozygote was significantly predominant in patients with
      colorectal cancer (18.4%) compared to control subjects (9.8%) (p < 0.01), whereas
      there was inverse association in TNFB*2/TNFB*2. However, the association between
      colorectal cancer and TNFA genotypes was not found which indicates that these
      alleles did not appear to be a susceptibility factor for colorectal cancer. TNFB
      polymorphism was not associated with a clinicopathological parameter of
      colorectal cancer. However, in regard to the degree of recurrence during the
      postoperative survival period, TNFB*1/TNFB*1 (12.5%) and TNFB*1/TNFB*2 (24%) were
      higher than TNFB*2/TNFB*2 (8.3%). Based on these results, it indicates that
      TNFB*1/TNFB*1 genotypes show an increased risk for colorectal cancer, and that
      the TNFB*1 allele (R.R. = 1.41) mediates some role in the initial step of
      tumorigenesis or activation of dormant tumor cells, whereas TNFB*2 allele
      mediates some functions associated with cytotoxicity of tumor cells.

PMID- 9638660
TI  - Cerebrospinal fluid investigations for neurometabolic disorders.
AB  - Careful clinical delineation and advances in analytical methods have opened new
      possibilities for the detection of inherited neurometabolic disorders, some of
      which require specific CSF analyses for diagnosis. Although patients suffering
      from these disorders have recognizable phenotypes, there are strong indications
      that remain many undiagnosed, leading to a continuation of futile diagnostic
      searches and, for most disorders, withholding of available rational therapy. As
      there is still widespread uncertainty about when to perform specialist CSF
      investigations, it is the aim of this paper to define the place for CSF
      investigations in the diagnostic work-up of a child with an encephalopathy of
      unknown origin. Most neurometabolic disorders can be identified through serum,
      plasma and urine analyses in conjunction with neuroradiological investigations.
      Whenever CSF investigations are performed, the analysis should include
      quantitative determination of lactate, pyruvate and amino acids, the latter by
      methods especially suited for CSF, in addition to cells, glucose, protein,
      immunoglobulin classes, specific immunoglobulins, and an evaluation of the blood
      brain barrier. If the disease course is non-progressive or if extracerebral
      symptoms are present in addition to an encephalopathy, e.g. endocrinological,
      hepatic, muscular or renal symptoms, investigations of metabolites in CSF over
      and above lactate, pyruvate and amino acids are generally noncontributary.
      Specific CSF investigations, which are discussed in detail, test metabolic
      pathways of brain metabolism, especially of neurotransmission. For a successful
      diagnosis of these defects, analyses must be planned individually, before CSF
      samples are taken, based on family history, clinical findings and disease course.
      Different determinations require different logistics from taking of the sample to
      shipment. One indication for specialized CSF analyses including biogenic
      monoamines and GABA is severe neonatal/infantile epileptic encephalopathy. In
      addition to a therapeutic trial of B6, folinic acid should be tried empirically
      for two to three days as the emerging syndrome of folinic acid responsive
      seizures appears to be the underlying cause in a sizable proportion of patients.
      In later infancy and childhood, defects in the metabolism of the biogenic
      monoamines may be suspected in patients with (fluctuating) extrapyramidal
      disorders, in particular Parkinsonism dystonia or more general "athetoid cerebral
      palsy", and vegetative disturbances. A severe epileptic encephalopathy and
      progressive mental retardation may be present. Neuroimaging findings do not show
      specific lesions. Determinations of folates and organic acids in CSF appear at
      present only warrantable individually in special constellations, e.g. classical
      clinical findings and disease course suggestive of glutaryl-CoA dehydrogenase
      deficiency with repeated negative quantitative analyses of organic acids in
      urine. The diagnosis of disorders, which require specific analyses of CSF, can
      only be achieved by conscious diagnostic decisions based on a concept of the
      respective disease and repeated scrupolous expert clinical evaluation aided by an
      array of investigations in blood and urine as well as neuroimaging findings. No
      single one investigation in CSF can serve as a "selective screening" test. A
      growing awareness of these disorders is needed and should lead to increased and
      earlier diagnosis of patients through fewer rather than more lumbar punctures.

PMID- 9638661
TI  - SIDS, abnormal nighttime REM sleep and CNS immaturity.
AB  - SIDS (Sudden Infant Death Syndrome) is the major cause of death in young,
      apparently healthy, infants, yet its etiology and pathogenesis remain unknown.
      SIDS peaks at 2-4 months, is more prevalent in the winter months and typically
      occurs in the early morning hours when most babies are asleep, suggesting that
      sleep may be part of the pathophysiological mechanism of SIDS. The sleep patterns
      of infants at high risk for SIDS were analyzed to test the hypothesis that there
      are abnormalities specific to nighttime sleep which may be indicative of a
      central nervous system (CNS) deficit that contributes to a high frequency of SIDS
      during the night. Electrophysiological sleep variables were recorded at monthly
      intervals in 1-6 months-old infants during the peak age of SIDS. The risk group
      (R) was resuscitated from a potentially life-threatening Sudden A-Ventilatory
      Event (S.A.V.E.) and compared to a group of control infants (C) with no family
      history of SIDS. The data representing four equal time intervals from 11 p.m.-11
      a.m. show an abrupt, statistically significant increase in REM sleep from 2-5
      a.m. in R infants. In C infants, time spent in REM sleep after 2 a.m. becomes
      progressively shorter while NREM sleep is proportionately longer. From 11 p.m.-2
      a.m., however, R and C infants do not differ either in the duration or in the
      percent of total sleep time (TST) of REM sleep. We hypothesize that these REM
      sleep abnormalities in vulnerable infants are indicative of a pervasive CNS
      immaturity. The higher prevalence of SIDS in the cold winter months and in the
      early morning hours, when darkness is prolonged, is discussed in relation to the
      possible involvement of the circadian rhythm of melatonin.

PMID- 9638662
TI  - Impaired visual perceptual performance on an object recognition task in children
      with cerebral visual impairment.
AB  - Visual perceptual ability and grating acuity were studied in 22 children with
      cerebral visual impairment (CVI). In most studies indicating visual perceptual
      impairments in CVI children, the evidence is weakened by the co-presence of
      reduced nonverbal, relative to verbal, intelligence, which in itself might
      account for the impaired performance on visual perceptual tasks. Our aim was to
      show that CVI children's performance on a visual perceptual task is weaker than
      can be expected from their nonverbal intelligence scores, thus demonstrating an
      impairment that is specific to visual perception. To this end, we used an object
      recognition task consisting of 60 line drawings depicting common objects in
      various aberrant ways. For each drawing, the age was established at which 9 out
      of 10 normal children could recognise the object depicted. This information was
      used to select the subset of drawings appropriate for each of the CVI subjects'
      nonverbal intelligence level, expressed as an age equivalent. Recognition
      performance on this subset of drawings was impaired in 16 children (72.7%), but
      was unrelated to visual acuity. We conclude that these children have a specific
      visual perceptual impairment, which is not reducible to any nonverbal
      intelligence impairments they might suffer.

PMID- 9638663
TI  - Magnetic resonance imaging of the brain in premature infants during the neonatal
      period. Normal phenomena and reflection of mild ultrasound abnormalities.
AB  - An MRI study was performed in 34 preterm infants who were clinically and
      neurologically normal and whose cranial ultrasound revealed no or only mild
      abnormalities. The postconceptional age at MRI varied between 30.6 and 37 weeks.
      The purpose of the study was to evaluate the significance of periventricular
      changes in signal intensity on MRI, comparing MRI with ultrasound. T1-weighted
      and T2-weighted images were assessed for changes in signal intensity of the
      periventricular white matter relative to the remainder of the cerebral
      hemispheric white matter. Cerebral MRIs of 13 postterm infants were additionally
      investigated. In all preterm infants small localized areas of high signal
      intensity on T1-weighted images and low signal intensity on T2-weighted images
      were seen adjacent to the frontal horns of the lateral ventricles. They faded
      with increasing age and were no longer seen one month after term in the group of
      postterm infants. The areas were considered normal before term age and probably
      represent remnants of the germinal matrix. Periventricular echodensities
      corresponded with a zone of changed signal intensity within the periventricular
      white matter on MRI. MRI signal change correlated with the presence and location
      of echodensities; the MRI signal changes slowly faded away after the
      echodensities disappeared.

PMID- 9638664
TI  - Marinesco Sjogren syndrome with rhabdomyolysis. A new subtype of the disease.
AB  - Four children from two families with characteristics of Marinesco-Sjogren
      syndrome (congenital cataract, ataxia) are presented. All children had clinical
      and neurophysiological signs of a demyelinating polyneuropathy. Three of them
      developed acute rhabdomyolysis with marked weakness and CK levels of up to 40,000
      U/I following a viral infection. In all children CK levels returned to normal
      within two weeks. Symptoms were recurrent in one of the children and resulted in
      a severe disability. In two other children recovery of motor function took about
      a month following the first attack. Metabolic disorders of the muscle were
      excluded by pathobiochemical examination of a muscle biopsy in one of the
      children. In conclusion, acute rhabdomyolysis can occur as a neuromuscular
      complication of Marinesco-Sjogren syndrome.

PMID- 9638665
TI  - Combined therapy of medulloblastoma: review of 46 patients treated in a single
      institution.
AB  - Medulloblastoma is the most frequent malignant brain tumor in pediatric patients.
      Early treatment strategies, combining surgery and radiotherapy alone, resulted in
      survival rates of about 40% only. In the last 15 years, chemotherapy was used
      more frequently in combination with surgery and radiotherapy. The rationale was
      to increase the survival rate and to decrease radiation toxicity in young
      children. Forty-six patients younger than 16 years were treated between July 1977
      and September 1995 in our institution (32 boys and 14 girls). Thirty-nine
      patients could be evaluated according to their postoperative treatment with
      regard to different protocols such as SIOP 1, SIOP 2, HDMTX/VCR, HIT protocol
      89/91 and Carbo-PEI (one patient). In total, 21/39 patients are alive without
      evidence of disease (EFS 55 +/- 7%) with a follow-up of 26 to 210 months. Four
      children are lost to follow-up. Twelve patients died after relapse, 1 child died
      of MTX-induced brain atrophy, 1 patient developed a secondary malignancy (acute
      lymphoblastic leukemia) and died. The best results were seen in patients treated
      according to the HIT 89/91 protocol as first-line treatment (CR 9/10). The
      improvement in outcome of our patients with medulloblastoma in recent years
      suggests the benefit of intensified chemotherapy on survival. In addition,
      refinement in surgical and radiological treatment have certainly also contributed
      to the better results.

PMID- 9638666
TI  - A case of myasthenia gravis in childhood associated with chronic inflammatory
      demyelinating polyradiculoneuropathy.
AB  - We report a 14-year-old girl who developed chronic inflammatory demyelinating
      polyradiculoneuropathy (CIDP) during the course of myasthenia gravis. Myasthenia
      gravis, which was clinically of ocular type, but with waning phenomenon of the
      extremities, occurred at 2 years and 4 months of age. Muscle weakness of the
      lower extremities gradually developed over the next 6 years. The
      electrophysiological and pathological findings fulfilled the criteria of
      "possible CIDP" with severe axonal involvement. The signs of myasthenia gravis
      and CIDP fluctuated synchronously. A common immunological abnormality was
      suggested to underlie this rare association of myasthenia gravis and CIDP in
      childhood.

PMID- 9638667
TI  - An algorithm for correction of distortion in stereotaxic digital subtraction
      angiography.
AB  - An algorithm for correction of the geometrical distortion in digital subtraction
      angiography (DSA) images was developed. Originally invented for 3D X-ray
      angiography, the algorithm was implemented in a computer program designed to
      fulfil the specific needs of stereotaxic DSA. The algorithm is based on
      transformation of an image of a grid from a distorted image back into its
      original pattern. The same transformation is then applied pixel-by-pixel to the
      angiographic images, which are acquired in direct conjunction with the grid
      image, without moving the gantry. The algorithm was tested in phantom studies and
      in the clinical situation with seven patients in ten examinations. Comparisons
      were made between co-ordinate determinations made on conventional full-size cut
      film and those performed on uncorrected and corrected DSA images, using 30- and
      23-cm fields of view. With our method of measurement we could not shown any
      remaining geometric distortion in the corrected DSA images. This distortion
      correction can, if properly applied, be used for high-precision stereotaxic DSA.

PMID- 9638668
TI  - Cerebrospinal fluid flow waveforms: effect of altered cranial venous outflow. A
      phase-contrast MR flow imaging study.
AB  - Our purpose was to assess the effect of alterations in the cranial venous outflow
      on cerebrospinal fluid (CSF) flow waveforms using phase-contrast MRI. Thirteen
      healthy subjects were assessed for CSF flow and cerebral vascular flow at the C2
      3 level, both before and after jugular venous compression (JVC). The flow
      waveforms were assessed both as an aggregate, and after dividing subjects in two
      groups based on percent jugular venous flow (PJVF) i.e. jugular outflow expressed
      as percent of cerebral arterial inflow. Group 1:7 subjects with PJVF more than
      and including median (predominantly jugular outflow); Group 2:6 subjects with
      PJVF less than median (predominantly extra-jugular outflow). CSF waveforms: JVC
      produced rounding of contours and flattening of dicrotic waves, with the effect
      being greater in group 1 than group 2. In group 1, systolic upslopes of the
      waveforms increased. No significant aggregate amplitude changes were noted;
      amplitudes increased in group 1 (P = 0.001), and decreased in group 2 (P = 0.03).
      Temporal interval to the maximum CSF systolic flow significantly increased in
      group 1. Vascular flow: Arterial flow significantly decreased in group 1. Jugular
      flow significantly decreased in both groups. The results suggest that CSF flow
      waveforms are sensitive to alterations in the cranial venous outflow. Changes in
      group 1 are most likely because of an elevation in intracranial pressure.
      Analysis of CSF flow waveforms appears a promising noninvasive tool for
      assessment of cranial compartment.

PMID- 9638669
TI  - Optimisation of unenhanced MRI for detection of lesions in multiple sclerosis: a
      comparison of five pulse sequences with variable slice thickness.
AB  - We used five MRI sequences in six patients with multiple sclerosis (MS):
      conventional spin-echo (CSE) with 5-mm slices; 2D fast spin-echo (FSE) with 2-mm
      slices; multishot T2*-weighted echo-planar imaging (EPI) with 5-mm slices; fast
      fluid-attenuated inversion recovery (fFLAIR) with 2-mm slices; and 3D fast spin
      echo with 1.5-mm-thick slices. A total of 225 lesions were detected on CSE, 274
      on 2D FSE, 137 on EPI, 385 on fFLAIR and 320 on 3D FSE. The EPI sequence was
      clearly the least sensitive and susceptibility artefact was a problem,
      particularly in the brain stem and temporal lobes. Fast FLAIR displayed a much
      higher number of supratentorial lesions (380) than 3D FSE (297), 2D FSE (264) or
      CSE (211). However, in the posterior cranial fossa 3D FSE was the most sensitive
      sequence (23 lesions), followed by CSE (14) and 2D FSE (10), while fFLAIR (5) was
      extremely insensitive.

PMID- 9638670
TI  - Subcortical frontal lesions on MRI in patients with motor neurone disease.
AB  - MRI was performed in 32 patients with motor neurone disease (26 men and 6 women,
      aged 40-77 years) and in a control group of 21 subjects. Of the patients studied,
      19 had definite and 11 probable amyotrophic lateral sclerosis (ALS) and two had
      progressive bulbar palsy. In 10 patients there were asymmetrical bilateral foci
      of increased signal intensity on proton-density and T2-weighted images, confined
      to the white matter. Two patients had only cortical frontal atrophy and slightly
      increased ventricular size, whereas 20 had normal MRI. The focal lesions were not
      confined to corticospinal tracts, but were also observed in subcortical frontal
      areas. While the lesions along the corticospinal tracts correspond to pyramidal
      tract degeneration, the subcortical foci correlate with degeneration of the
      frontal bundles and indicate generalised involvement of the central nervous
      system.

PMID- 9638671
TI  - MRI features of choroid plexitis.
AB  - Four cases of choroid plexitis of the brain (two with cryptococcosis and two with
      tuberculosis) are presented. The four patients showed either unilateral
      enlargement (3) or bilateral enlargement (1) and dense enhancement of the choroid
      plexus in the lateral ventricles (4) and fourth ventricle (1) in association with
      clinical findings of leptomeningitis. All patients had unilateral cystic
      dilatation of the temporal horn of the lateral ventricle presumably secondary to
      entrapment of the temporal horn and extensive oedema around the ipsilateral
      ventricle.

PMID- 9638672
TI  - Amyloid angiopathy causing widespread miliary haemorrhages within the brain
      evident on MRI.
AB  - The case of a 70-year-old woman with cerebral amyloid angiopathy (CAA) is
      presented. MRI of the head showed widespread miliary foci of haemorrhage within
      the cerebrum and cerebellum, with some additional linear lesions within the
      cerebral cortex and patchy lesions in the white matter. This is in contrast to
      the more usual pattern of intracranial haemorrhage in CAA, i.e., a lobar
      haematoma.

PMID- 9638673
TI  - Secondary superficial siderosis of the central nervous system in a patient
      presenting with sensorineural hearing loss.
AB  - We present a 50-year-old man who was investigated for sensorineural hearing loss.
      On MRI of the brain superficial siderosis of the central nervous system was seen,
      while MRI of the spine revealed an ependymoma of the cauda equina. This case
      illustrates the importance of performing T2-weighted imaging of the brain and
      posterior fossa when sensorineural hearing loss is present. Spine imaging is
      mandatory when superficial siderosis of the brain is diagnosed without
      identification of a bleeding source in the brain.

PMID- 9638674
TI  - 1H MR spectroscopy of the basal ganglia in childhood: a semiquantitative
      analysis.
AB  - Proton MR spectra of the basal ganglia were obtained from 28 patients, 24 male
      and 14 female, median age 16.3 months (5 weeks to 31 years). They included 17
      patients with normal MRI of the basal ganglia without metabolic disturbance
      (control group) and 11 patients with various metabolic diseases: one case each of
      high serum sodium and high serum osmolarity, cobalamin C deficiency, Leigh
      disease, Galloway-Mowat syndrome, Pelizaeus-Merzbacher disease, hemolytic-uremic
      syndrome and Wilson disease and two cases of Alagille syndrome and methylmalonic
      acidemia with abnormal MRI of the basal ganglia or blood or urine analysis
      (abnormal group). The MR spectrum was measured by using STEAM. The MR-visible
      water content of the region of interest was obtained. Levels of myoinositol,
      choline, creatine and N-acetylaspartate were measured using a semiquantitative
      approach, with absolute reference calibration. In the control group, there was a
      gradual drop of water content over the first year of life; N-acetylaspartate,
      creatine and myoinositol levels showed no significant change with age, in
      contrast to the occipital, parietal and cerebellar regions. Choline showed a
      gradual decrease for the first 2 years of life and then remained fairly constant.
      In the abnormal group the water content was not significantly different. N
      Acetylaspartate was decreased in patients with high serum sodium and high serum
      osmolarity, cobalamin C deficiency, Leigh disease and one case of methylmalonic
      acidemia. Decreased creatine was also found in Leigh disease, and decreased
      choline in Galloway-Mowat syndrome and Wilson disease. Myoinositol was elevated
      in the patient with abnormally high serum sodium, and decreased in the hemolytic
      uremic syndrome.

PMID- 9638675
TI  - Cerebellar arteriovenous malformations in children.
AB  - We review the presentation, imaging findings and outcome in 18 children with
      cerebellar arteriovenous malformations (AVM). This group is of particular
      interest because of the reported poor outcome despite modern imaging and
      neurosurgical techniques. All children had CT and 15 underwent catheter
      angiography at presentation. Several of the children in the latter part of the
      study had MRI. Of the 18 children, 17 presented with a ruptured AVM producing
      intracranial haemorrhage. The remaining child presented with temporal lobe
      epilepsy and was shown to have temporal, vermian and cerebellar hemisphere AVM.
      This child had other stigmata of Osler-Weber-Rendu syndrome. Three other children
      had pre-existing abnormalities of possible relevance. One had a vascular
      malformation of the cheek and mandible, one a documented chromosomal abnormality
      and another a midline cleft upper lip and palate. Six of the 17 children with a
      ruptured cerebellar AVM died within 7 days of the ictus. Vascular pathology other
      than an AVM was found in 10 of the 14 children with a ruptured cerebellar AVM who
      had angiography: 4 intranidal aneurysms, 5 venous aneurysms and 2 cases of venous
      outflow obstruction (one child having both an aneurysm and obstruction). The
      severity of clinical presentation was directly related to the size of the acute
      haematoma, which was a reasonable predictor of outcome.

PMID- 9638676
TI  - CT and MRI of microcephalia vera.
AB  - CT and MRI findings in three patients, two of them siblings, with microcephalia
      vera are presented. In this rare entity, a very small brain with an extremely
      thin, smooth cortex and increase surrounding cerebrospinal fluid are observed.

PMID- 9638677
TI  - Imaging of huge lingual thyroid gland with goitre.
AB  - We present the CT and MRI findings in a 75-year-old woman with a huge
      pathologically proven lingual thyroid which underwent goitrous degeneration. CT
      and MRI showed a midline, tongue-based, exophytic mass with areas of necrosis and
      heterogeneous contrast enhancement, as seen in large goitres in the normal
      thyroid gland.

PMID- 9638678
TI  - Transmural migration of an intracavernous carotid detachable balloon used to
      control surgically induced haemorrhage.
AB  - We report a case in which a balloon detached in the carotid siphon for control of
      iatrogenic bleeding migrated to the oesophagus. We discuss the pathophysiology.

PMID- 9638679
TI  - Transplacental cocaine exposure. 1: A rodent model.
AB  - To characterize the transplacental effects of cocaine on the developing brain, we
      have developed a mouse model of gestational cocaine exposure. Pharmacokinetic
      analysis revealed that cocaine and its metabolites (BE, BNE, and NC) were found
      in fetal brain and plasma at 30 and 120 min following SC administration to
      embryonic day (E) 17 pregnant Swiss Webster mice. Pregnant dams injected twice
      daily with cocaine HCl at 20 mg/kg SC from gestational day E8 to E17 (COC)
      demonstrated less food intake and lower percentage weight gain than vehicle
      injected dams allowed access to food ad lib (SAL). A nutritionally paired control
      group of dams injected with saline vehicle and pair-fed with the COC dams (SPF)
      demonstrated the lowest percentage weight gain of all three groups. The surrogate
      fostered offspring of COC and SPF dams demonstrated persistent growth retardation
      [on postnatal days (P) 1, P9, and P50] and transient brain growth retardation (on
      P1 and P9) when compared to pups born to SAL dams. We conducted behavioral tests
      that allowed us to dissociate the indirect effect of cocaine-induced malnutrition
      from a direct effect of prenatal cocaine administration in altering postnatal
      behavior. Pups from all three groups were tested for first-order Pavlovian
      conditioning on P9 or P12, or for the ability to ignore redundant information in
      a blocking paradigm on P50 or P100. Unlike the SPF and SAL controls, COC mice
      (i.e., mice born to COC dams) were unable to acquire an aversion to an odor
      previously paired with shock on P9. This learning deficit was transient because
      on P12, COC mice trained on the same conditioning task displayed an aversion to
      the odor that was indistinguishable from the SPF and SAL controls. P50 and P100
      COC mice (and to a lesser extent, SPF mice) demonstrated a persistent behavioral
      deficit in the blocking paradigm, which may reflect alterations in selective
      attention. We discuss how these findings in our rodent model have developmental
      implications for human infants exposed to cocaine in utero.

PMID- 9638680
TI  - Transplacental cocaine exposure. 2: Effects of cocaine dose and gestational
      timing.
AB  - We have utilized a mouse model of transplacental cocaine exposure to investigate
      the effects of cocaine dose and gestational timing in altering brain and body
      growth and postnatal behavior in exposed offspring. Pregnant dams were injected
      with cocaine HCl at 40 mg/kg/day (COC 40) or 20 mg/kg/day (COC 20), or 10
      mg/kg/day (COC 10) SC from embryonic day (E) 8 to E17, or cocaine HCl at 40
      mg/kg/day SC from E8 to E13 (COC Early) or from E13 to E17 (COC Late) divided in
      two daily doses. COC 40 and COC Late dams, as well as dams in nutritionally
      paired control groups (injected with saline vehicle and pair-fed with the COC
      dams: SPF 40, SPF 20, SPF 10), demonstrated less weight gain than SAL controls
      (injected with saline vehicle and allowed access to food ad lib). The surrogate
      fostered offspring of COC 40 and SPF 40 dams demonstrated brain and body growth
      retardation [on postnatal day (P) 1 and P9] when compared to pups born to SAL
      dams. Offspring of COC Late, SPF 20, and SPF 10 dams demonstrated brain and body
      growth retardation on P1 when compared to pups born to SAL dams. Pups from all
      groups were tested for first-order Pavlovian conditioning on P9, or for the
      ability to ignore redundant information in a blocking paradigm on P50. Only COC
      40 mice (i.e., offspring born to COC 40 dams) were unable to acquire an aversion
      to an odor previously paired with shock on P9. When compared with SAL controls,
      COC 40 mice (and to a less significant extent SPF 40 mice) demonstrated a
      persistent behavioral deficit in the blocking paradigm on P50, which may reflect
      alterations in selective attention. Correlation analyses indicated that the dose
      and gestational timing of transplacental cocaine exposure, and varying degrees of
      malnutrition, had effects on blocking performance, with greater prenatal cocaine
      exposure and increased prenatal malnutrition resulting in more significant
      behavioral impairments. A path regression analysis demonstrated independent and
      significant effects of prenatal cocaine as well as prenatal malnutrition in
      contributing to impaired performance in the blocking paradigm. As suggested by
      the clinical literature, our preclinical data support a model whereby the dose
      and duration of prenatal cocaine exposure have direct effects on offspring brain
      and body growth and on behavioral performance.

PMID- 9638681
TI  - Transplacental cocaine exposure. 3: Mechanisms underlying altered brain
      development.
AB  - In a mouse model of transplacental cocaine exposure we have demonstrated
      alterations in brain structure and function of offspring including disturbances
      of brain growth, disruption of neocortical cytoarchitecture, and transient as
      well as persistent behavioral deficits. One mechanism by which cocaine may alter
      fetal brain development is through cocaine-induced alpha-adrenergic-mediated
      (uterine) arterial vasoconstriction. In this study pregnant Swiss Webster (SW)
      mice were injected with cocaine HCl (20 or 40 mg/kg, SC) without any changes
      evident in mean arterial blood pressure (MAP) measurements. These physiology
      results suggest that in our mouse model, cocaine's transplacental effects on the
      fetus are not due to cocaine-induced maternal vasoconstriction, nor concomitant
      hypoperfusion of the fetus. In a separate series of experiments, pregnant SW dams
      were administered cocaine HCl at 40 mg/kg/day (COC 40), 20 mg/kg/day (COC 20), or
      10 mg/kg/day (COC 10) [SC, divided in two daily doses, from embryonic day (E) 8
      to E17 inclusive]. Additional groups of cocaine-treated dams were administered
      phentolamine (5 mg/kg, SC), a short-acting alpha-adrenergic antagonist, 15 min
      prior to each cocaine dose (Phent COC 40, Phent COC 20, Phent COC 10). Animals
      born to Phent COC 40 dams demonstrated transient postnatal brain growth
      retardation and behavioral deficits in first-order conditioning of P9 mice
      comparable to mice born to COC 40 dams, which received the same regimen of
      cocaine injections without phentolamine pretreatment. Like COC 40 offspring,
      Phent COC 40 offspring also demonstrated a persistent deficit in the blocking
      paradigm. The behavioral and growth findings confirm and extend the physiology
      data, and imply that in our rodent model, alpha-adrenergic mechanisms (including
      maternal vasoconstriction) are unlikely to mediate these toxic effects of
      transplacental cocaine exposure on developing brain.

PMID- 9638682
TI  - Neurobehavioral and pregnancy effects of prenatal zidovudine exposure in Sprague
      Dawley rats: preliminary findings.
AB  - In 1994, the Public Health Service made prenatal zidovudine (ZDV, AZT) the
      standard of care to prevent mother-to-child transmission of HIV. The current
      study was undertaken to determine if prenatal exposure to ZDV has an impact on
      pregnancy outcomes, birth anomalies, or offspring behavior in an animal model
      using Sprague-Dawley (SD) rats. Thirty-one virgin female SD rats were mated and
      randomly assigned to receive either ZDV at 150 mg/kg/day or vehicle via gastric
      intubation for 22 days starting on gestation day (G) 1. On G 22, teratologic
      examination of 12 litters showed no gross structural malformations. There were no
      significant differences between the groups for maternal food and water
      consumption or maternal weight gain across pregnancy. However, ZDV treatment
      significantly reduced litter size and increased birth weights for both male and
      female pups. One developmental milestone, pinna detachment, occurred
      significantly earlier in the ZDV-exposed male pups compared to the vehicle
      intubated male controls. On day 21-22 of life, pups in each litter were injected
      with one of four doses of amphetamine and were observed for behavioral activity
      in a photobeam-based activity monitor for 1 h. Overall amphetamine increased
      activity and decreased thigmotaxis or wall-hugging behavior. ZDV treatment
      increased the locomotor response to amphetamine in females only and dampened the
      action of amphetamine to decrease thigmotaxis in both genders. Further studies
      are warranted to determine the threshold dose at which these changes occur, the
      duration of the effects, as well as the neurochemical system(s) responsible for
      the altered amphetamine responses.

PMID- 9638683
TI  - Neurobehavioral changes in shoe manufacturing workers.
AB  - A study was carried out to evaluate: (a) the value of a cumulative exposure
      estimate (CEE) calculated from limited information on air concentration; and (b)
      whether chronic exposure to mixed organic solvents at a shoe manufacturing
      factory has induced neurobehavioral changes. The Neurobehavioral Core Test
      Battery was administered to 40 female workers from a shoe manufacturing factory
      and 28 housekeepers as referents. The airborne concentrations of the solvents as
      a mixture were 0.46-0.71 at the frame making process and 1.83-2.39 at the
      adhesive process. Performance was analyzed by three exposure indices: current
      department, exposure duration, and CEE. The Santa Ana Dexterity test showed
      statistically significant differences only in CEE. In particular, the group with
      higher exposures had a significantly poorer performance than the reference group,
      on preferred hand trials. The results suggested that CEE appeared to be a better
      indicator of mixed organic solvents exposure, and neurobehavioral changes were
      associated with CEE over 10 years.

PMID- 9638684
TI  - CYP2D1 polymorphism in methamphetamine-treated rats: genetic differences in
      neonatal mortality and effects on spatial learning and acoustic startle.
AB  - d-Methamphetamine (MA) is one of more than two dozen drugs included in the
      cytochrome P450-mediated "debrisoquine oxidation polymorphism" panel. The human
      gene (CYP2D6) is responsible for the "poor metabolizer" (PM) and "extensive
      metabolizer" (EM) phenotypes for drugs such as MA; a similar polymorphism (the
      CYP2D1 gene) exists in rats. Female Black or Dark Agouti rats exhibit the PM
      phenotype, whereas Sprague-Dawley (SD) rats show the EM trait. We sought to test
      the possibility that these strains of rats might exhibit altered MA-induced
      developmental neurotoxicity. Neonatal exposure to MA on days 11-20 has previously
      been shown to induce spatial learning deficits in Sprague-Dawley rats when tested
      as adults. Therefore, in the present experiment, on postpartum days 11 through
      20, ACI (Black Agouti) and SD progeny were administered 30 mg/kg MA twice daily.
      MA treatment caused larger increases in mortality in ACI than in SD rats,
      suggesting that decreased MA metabolism leads to enhanced toxicity and lethality.
      Female offspring were assessed behaviorally as adults. No differences were
      observed in acoustic startle or straight swimming channel performance. In the
      Morris maze, both MA-treated rat strains showed longer latencies to find the
      hidden platform during acquisition, reinstatement, and shift trials, and spent
      less time in the target quadrant on probe trials; no strain differences in
      learning were found. Although these data do not support our hypothesis that MA
      induced developmental neurotoxicity might be enhanced in the ACI rat, this
      interpretation is tempered by the high mortality rate (65%) of MA-treated ACI
      neonates, suggesting a possible "survivor effect" in this strain.

PMID- 9638685
TI  - Lack of effect of methylmercury exposure from birth to adulthood on information
      processing speed in the monkey.
AB  - Although it is established that developmental methylmercury exposure produces
      severe motor and sensory impairment, the effect on cognitive function is less
      clear. To explore this issue, monkeys with robust methylmercury-induced deficits
      in visual, auditory, and somatosensory function were tested on a series of tasks
      assessing central processing speed, which is highly correlated with intelligence
      in humans. Five monkeys (Macaca fascicularis) were dosed from birth to 7 years of
      age with 50 micrograms/kg/day of mercury as methylmercuric chloride. Blood
      mercury levels were stable at 0.8-1.1 micrograms/g until cessation of dosing.
      When they were 20 years old, these monkeys and four age- and rearing-matched
      controls were tested on a series of simple and complex reaction time tasks. The
      monkey sat in a primate chair with a stainless steel bar centered at waist
      height. Four push buttons equidistant from the steel bar were mounted on a
      vertical Plexiglas panel in front of the monkey. The monkey was required to make
      contact with the bar, then release the bar and push the appropriate button in
      response to a change in stimulus conditions. For the first task (simple reaction
      time), the monkey was required to respond on a button when it changed from unlit
      to red. The monkey then performed a sequence of complex reaction time tasks: two
      button, four-button, and several tasks of increasing complexity using four
      buttons and multiple colors. For each task, the latency to release the bar after
      the stimulus change (central processing speed) and to move the hand from the bar
      to the button (motor speed) were determined. Lastly, the monkey was required to
      make the quickest possible motor response on the simple reaction time task. There
      were no differences between groups on any aspect of the experiment. These data
      provide further evidence for absence of cognitive impairment in monkeys exposed
      developmentally to methylmercury.

PMID- 9638686
TI  - Binge neonatal alcohol intubations induce dose-dependent loss of Purkinje cells.
AB  - Previous work using artificial rearing methods to administer alcohol to neonatal
      rats identified postnatal days (PD) 4-6 as a period of enhanced vulnerability to
      alcohol-induced Purkinje cell loss. To develop an alternative to artificial
      rearing, alcohol was administered to pups in a binge pattern of exposure using
      acute intubations, and dose-related effects on blood alcohol concentrations
      (BACs), somatic growth, and cerebellar Purkinje cell survival were assessed. Pups
      were intubated with alcohol in milk formula, twice a day, 2 h apart, with total
      daily doses of 4.5, 5.25, or 6.0 g/kg of alcohol. After intubations on PD 4, the
      blood alcohol concentration (BAC)-time curves systematically increased with
      increasing dose. Intubation of these doses on PD 4-6 produced significant, dose
      dependent reductions in the total number of cerebellar Purkinje cells on PD 10,
      counted using the stereological optical fractionator. Somatic growth was
      significantly affected only by the highest dose. These dose manipulations using
      intubations confirmed that Purkinje cell death systematically increased as a
      function of BAC profiles within the PD 4-6 window of vulnerability.

PMID- 9638687
TI  - Differential effects on cognitive functioning in 9- to 12-year olds prenatally
      exposed to cigarettes and marihuana.
AB  - Cognitive performance was examined in 131 9-12-year-old children for whom
      prenatal marihuana and cigarette exposure had been ascertained. The subjects,
      participants in an ongoing longitudinal study, were from a low-risk,
      predominantly middle class sample. The tasks included the WISC-III and a series
      of tests assessing aspects of cognition subsumed under the rubric of executive
      function. Consistent with results obtained at earlier ages, discriminant function
      analysis revealed a dose-dependent association, which remained after controlling
      for potential confounds (including secondhand smoke), between prenatal cigarette
      exposure and lower global intelligence scores with the verbal subtests of the
      WISC maximally discriminating among levels of in utero exposure. In contrast,
      prenatal marihuana exposure was not associated with global intelligence or the
      verbal subtests. Rather, this drug was negatively associated with the executive
      function tasks that require impulse control and visual analysis/hypothesis
      testing and with a number of WISC subtests requiring the same abilities. The
      interpretation of these results is discussed in terms of executive function and
      is related to earlier observations of this sample and to the extant prefrontal
      and general marihuana literature.

PMID- 9638688
TI  - Long-term changes in rat social behavior following treatment with
      trimethylolpropane.
AB  - A potent convulsant, trimethylolpropane phosphate (TMPP), was evaluated for long
      term effects on measures of social behaviors and anxiety in Long-Evans rats.
      Animals received three to four daily treatments of TMPP (0.1 mg/kg/ml) beginning
      at age 23 days in Experiment 1 and 73 days in Experiment 2. Gregariousness was
      measured in juvenile play and adult social investigation. Anxiousness was
      measured in the open field and elevated plus-maze. Long-lasting changes in social
      behaviors were found: play and social investigation were elevated, especially in
      female rats. Also, an aversive environmental experience associated with TMPP
      treatment influenced the drug effect on social investigation for males, but not
      females. In males, TMPP- vs. VEH-treated animals displayed greater social
      investigation when the treatment was in a positive environment than in an
      aversive one. In contrast, TMPP- vs. VEH-treated females showed greater social
      investigation regardless of environmental experience. There were no treatment
      group differences for measures of anxiety. These results suggest short-term
      exposure to TMPP may lead to long-lasting changes in specific social behaviors
      and neural substrates related to them, but not to changes in anxiousness.

PMID- 9638689
TI  - Active oxygen species formation in synaptosomes exposed to an aluminum chelator.
AB  - This study evaluates the potential of two chelators, 1,2-dimethyl-3
      hydroxypyridine-4-one (Hdpp) and 1-n-butyl-2-methyl-3-hydroxypyridin-4-one
      (Hnbp), to modulate cerebral rates of free radical production. The fluorometric
      assay for 2',7'-dichlorofluorescein, which is formed by oxidation of a
      nonfluorescent precursor (2',7'-dichlorofluorescein diacetate), was used to assay
      reactive oxygen species (ROS) production. The chelator Hdpp alone and the
      aluminum complexes of each chelator, Al (dpp)3 and Al (nbp)3, all inhibited basal
      rates of generation of ROS within a rat cerebral synaptosomal fraction. In the
      presence of an iron salt (1 microM FeSO4), a major enhancement of synaptosomal
      ROS formation was apparent. However, with the addition of an equimolar
      concentration of Hdpp, Al(dpp)3, or Al(nbp)3, this stimulation was completely
      abolished. The N-substituted-3-hydroxy-4-pyridinones have been proposed to be of
      clinical utility for the removal of iron or aluminum from tissues. The clinical
      potential of this class of chelator may be enhanced by their ability to inhibit
      iron-related oxidative events.

PMID- 9638690
TI  - Combined effects of simultaneous exposure to toluene and ethanol on auditory
      function in rats.
AB  - Three experimental groups and one control group of Long-Evans rats were used to
      study the combined effects of toluene and ethanol on auditory function. The first
      experimental group was exposed to toluene vapors (1750 ppm, 6 h/day, 5 days/week,
      4 weeks), the second one was daily gavaged with a saline solution of ethanol (4
      g/kg, 4 weeks), and the last group was simultaneously exposed to both toluene and
      ethanol. Auditory function was tested by recording brain stem (inferior
      colliculus) auditory-evoked potentials for audiometric frequencies ranging from 2
      to 32 kHz. Urinary hippuric acid was dosed to check the toluene metabolism during
      the experiments. Ethanol clearly modified the toluene metabolism in the present
      experimental conditions. As a result, the hearing loss induced by a simultaneous
      exposure to both ethanol and toluene was larger than that induced by exposure to
      toluene alone.

PMID- 9638691
TI  - The lost generation.

PMID- 9638692
TI  - Atypical odontalgia.

PMID- 9638693
TI  - Cavernous hemangioma of the masseter muscle.

PMID- 9638694
TI  - Alloplastic temporomandibular joint reconstruction.

PMID- 9638695
TI  - Platelet-rich plasma: Growth factor enhancement for bone grafts.
AB  - Platelet-rich plasma is an autologous source of platelet-derived growth factor
      and transforming growth factor beta that is obtained by sequestering and
      concentrating platelets by gradient density centrifugation. This technique
      produced a concentration of human platelets of 338% and identified platelet
      derived growth factor and transforming growth factor beta within them. Monoclonal
      antibody assessment of cancellous cellular marrow grafts demonstrated cells that
      were capable of responding to the growth factors by bearing cell membrane
      receptors. The additional amounts of these growth factors obtained by adding
      platelet-rich plasma to grafts evidenced a radiographic maturation rate 1.62 to
      2.16 times that of grafts without platelet-rich plasma. As assessed by
      histomorphometry, there was also a greater bone density in grafts in which
      platelet-rich plasma was added (74.0% +/- 11%) than in grafts in which platelet
      rich plasma was not added (55.1% +/- 8%; p = 0.005).

PMID- 9638696
TI  - The validity of clinical examination for diagnosing anterior disk displacement
      with reduction.
AB  - OBJECTIVE: The objective of this study was to evaluate the diagnostic accuracy of
      a clinical examination for diagnosing anterior disk displacement with reduction.
      STUDY DESIGN: A series of 273 consecutive patients with temporomandibular
      disorders were clinically examined according to well-defined criteria. The
      patients were examined for clicking by digital palpation during maximal mouth
      opening and closing (the Clicking test). When clicking was identified, two
      additional tests were performed: one determined whether the clicking was
      eliminated at a protruded position, and the other determined whether the clicking
      became louder when the patient's mandible was manipulated toward the eminences.
      Bilateral magnetic resonance images were subsequently obtained from all patients;
      the clinical examination findings were then compared to the imaging-based
      diagnoses of the temporomandibular joint status to assess the diagnostic accuracy
      of the clinical findings. RESULTS: Although the predictability of identifying
      anterior disk displacement with reduction by clicking was relatively low, it
      increased to an acceptable level when the additional tests were used. The overall
      accuracy for the Clicking test combined with either of the other tests was about
      90%. CONCLUSION: Our results suggest that anterior disk displacement with
      reduction can be diagnosed with considerable accuracy through the use of a
      clinical examination only.

PMID- 9638697
TI  - The validity of clinical examination for diagnosing anterior disk displacement
      without reduction.
AB  - OBJECTIVE: The objective of this study was to evaluate the diagnostic accuracy of
      patient history and clinical signs as confirmed by magnetic resonance imaging
      examination for diagnosing anterior disk displacement without reduction. STUDY
      DESIGN: A series of 273 consecutive patients with temporomandibular disorders
      were clinically examined according to well-defined criteria. Patients were first
      asked if they had a history of clicking. The following clinical characteristics
      of anterior disk displacement without reduction were then assessed: (1) maximal
      mouth opening less than 40 mm; (2) deflection of the mandible to the affected
      side at the maximal mouth opening position; (3) limitation of condylar
      translation on palpation during maximal mouth opening; (4) preauricular pain
      during mandibular movements; and (5) crepitation. Bilateral magnetic resonance
      images were obtained for all patients, and the magnetic resonance imaging
      interpretation was compared with the clinical examination findings to assess the
      diagnostic accuracy of the clinical findings. RESULTS: The sensitivity was
      considerably low in contrast with the relatively high specificity for all six
      clinical parameters tested. The overall accuracies of the clinical parameters
      ranged from 71% to 81%. CONCLUSION: Our results suggest that the predictability
      of historical or clinical findings to differentiate anterior disk displacement
      without reduction from other diagnoses is not high.

PMID- 9638698
TI  - Design and preliminary evaluation of an extraoral Gow-Gates guiding device.
AB  - Incidence of unsuccessful anesthesia with the Gow-Gates mandibular block may be
      greater than that for the inferior alveolar nerve block until the administrator
      gains experience with this technique. The aim of this study was to develop a
      support instrument for the Gow-Gates mandibular block in an attempt to make the
      described procedure easier and more precise, especially for beginners. In a
      preliminary clinical experiment 40 patients were anesthetized with this new
      device; a control group of 40 patients was anesthetized without the instrument.
      The operators were 80 dental students without previous clinical experience in the
      Gow-Gates technique. In the experimental group 39 (97.5%) of the 40 patients were
      provided with complete anesthesia. In the control group 31 (77.5%) of the 40
      patients were completely anesthetized. It appears that the new device allows a
      great level of success with the Gow-Gates mandibular block, irrespective of the
      clinical experience of the operator.

PMID- 9638699
TI  - Effect of impact and injury characteristics on post-motor vehicle accident
      temporomandibular disorders.
AB  - OBJECTIVES: The objective of this study was to assess the potential effects of
      motor vehicle accident impact and injury characteristics on post-motor vehicle
      accident temporomandibular disorders in terms of presenting signs and symptoms,
      diagnoses, treatment regimens, and outcomes. STUDY DESIGN: A retrospective chart
      review of 50 patients with post-motor vehicle accident temporomandibular
      disorders from a private oral medicine practice was undertaken. Various
      demographic data and data related to temporomandibular disorders and motor
      vehicle accident impact and injury characteristics were collected. Chi-square and
      Fisher exact tests and multiple regression analyses were performed. RESULTS:
      Patients involved in front-end collisions or motor vehicle accidents resulting in
      severe vehicle damage reported more direct orofacial injury. However, those in
      rear-end collisions or accidents resulting in minimal vehicle damage required
      more treatment. Direct head or orofacial injury was therefore not a prognostic
      indicator. From multiple regression analyses, indicators of a poorer prognosis
      were minimal vehicle damage, lack of headrest use, driver position, and
      settlement of insurance claim. CONCLUSIONS: In this patients group several
      prognostic indicators for patients with post-motor vehicle accident
      temporomandibular disorders were identified; these indicators may influence the
      management approach for this patient population.

PMID- 9638700
TI  - Effect of muscle relaxation splint therapy on the electromyographic activities of
      masseter and anterior temporalis muscles.
AB  - The purpose of this study was to compare the effectiveness of splint therapy on
      the electromyographic activity of masticatory muscles (anterior temporalis and
      masseter) before and after the application of a muscle relaxation splint.
      Electromyography recordings from the masseter and anterior temporalis muscles
      were analyzed quantitatively during maximal biting in the intercuspal position
      both before and after treatment without a splint. Fourteen patients whose chief
      complaint was masticatory muscle pain were selected for the study. After the
      initial evaluations muscle relaxation splints were applied, and the patients were
      instructed to use the splints for 6 weeks. Surface electromyographic recordings
      were taken from each patient before the beginning of clinical therapy and after 6
      weeks of wearing the splints. The data obtained were analyzed through paired
      sample t tests and Wilcoxon's signed rank tests. The results of the study were as
      follows: (1) the electromyographic activity of the two muscles during maximal
      biting was not markedly changed after the muscle relaxation splint was used; and
      (2) the changes observed in electromyographic activity of the involved and
      noninvolved sides were insignificant as well.

PMID- 9638701
TI  - Caries in patients with non-insulin-dependent diabetes mellitus.
AB  - OBJECTIVE: The purpose of this study was to investigate the prevalence and risk
      factors of dental caries in patients with non-insulin-dependent diabetes mellitus
      and to determine whether these factors are associated with metabolic control and
      vascular complications of the disease. STUDY DESIGN: Both the occurrence of
      caries, acidogenic oral bacteria, and yeasts and salivary flow were studied in 25
      patients with non-insulin-dependent diabetes mellitus whose diagnosis had been
      set 13 to 14 years earlier and in whom the metabolic evolution of the disease was
      well established. The patients' glycemic control was determined by means of
      analysis of the blood hemoglobin A1C concentration at the time of dental
      examination. The control group consisted of 40 nondiabetic subjects in the same
      age group. Decayed, missing, and filled teeth indices and numbers of surfaces
      with caries, filled surfaces, and root caries were determined by means of
      clinical dental caries examination. Stimulated salivary flow was measured, and
      levels of Streptococcus mutans, lactobacilli, and yeasts were analyzed. RESULTS:
      The median hemoglobin A1C concentration of the patients was 8.6%, which indicates
      poor metabolic control of diabetes. No association was found between the
      metabolic control of disease and dental caries. The occurrence of dental caries
      was not increased in the patients with non-insulin-dependent diabetes mellitus in
      comparison with the control subjects. The counts of acidogenic microbes and
      yeasts did not differ statistically significantly between the groups. There was
      no association of caries with the prevalence of coronary artery disease or
      hypertension in either the patients or the control subjects. In a stepwise
      logistic regression model, a salivary flow of at least 0.8 ml/min was related to
      the occurrence of dental caries in patients with non-insulin-dependent diabetes
      mellitus, whereas negligence with respect to dental care was the most important
      risk predictor in the control group. CONCLUSION: Our results showed no effect of
      diabetes on the prevalence of caries. However, the caries-protective effect of
      saliva was partly lost in patients with non-insulin-dependent diabetes mellitus.

PMID- 9638702
TI  - Penetration of human vaginal and buccal mucosa by 4.4-kd and 12-kd fluorescein
      isothiocyanate-labeled dextrans.
AB  - In a previous study we demonstrated that human vaginal mucosa was as permeable to
      water as was buccal mucosa. Water, however, is a very small molecule with a
      molecular weight of 18 d. To further explore similarities between these two types
      of mucosa with respect to permeability, it was decided to investigate the passage
      of two large, hydrophilic molecules across these epithelia. Specimens of fresh,
      clinically healthy human vaginal and buccal mucosa were taken from excised tissue
      obtained during vaginal hysterectomies and various oral surgical procedures.
      Seven biopsy materials from each specimen were mounted in flow-through diffusion
      cells (exposed area, 0.039 cm2), and their permeability to 4.4- and 12-kd
      fluorescein-isothiocyanate-labeled dextrans was determined through use of a
      continuous flow-through perfusion system. Dextran was detected by means of a
      fluorospectrophotometric method at excitation and emission wave lengths of 498
      and 520 nm, respectively. Specimens were examined histologically before and after
      permeability experiments, and similarities between vaginal and buccal tissues
      were verified. No statistically significant differences between the flux values
      of the 4.4-kd dextran across vaginal and buccal mucosa were found. However, for
      the 12-kd dextran the flux rate across buccal mucosa was significantly higher
      than the rate across vaginal mucosa. These results demonstrate that human vaginal
      mucosa is for practical purposes as permeable as buccal mucosa to 4.4-kd
      hydrophilic molecules. This further supports the hypothesis that vaginal mucosa
      may be a useful model for studying the passage across buccal mucosa of chemical
      compounds and therapeutic agents that are less than approximately 4.4 kd in
      molecular mass. For a 12-kd dextran the flux rate across buccal mucosa is
      significantly higher than the flux rate across vaginal mucosa, and the model
      becomes inaccurate.

PMID- 9638703
TI  - Immunohistochemical evaluation of bcl-2 oncoprotein in oral dysplasia and
      carcinoma.
AB  - The proto-oncogene bcl-2 is associated with follicular lymphoma involving
      translocation t(14;18)(q32;q21) and is also overexpressed in various neoplasms.
      We report deregulation of bcl-2 expression during progression from oral
      epithelial dysplasia to squamous cell carcinoma. Immunohistochemical analysis
      with monoclonal antibodies to bcl-2 oncoprotein in formalin-fixed paraffin
      embedded tissue sections revealed that severe epithelial dysplasias had a higher
      percentage of immunoreactivity than did mild and moderate dysplasias and squamous
      cell carcinomas. Expression of this oncoprotein was directly proportional to the
      degree of epithelial dysplasia, and nondysplastic basal cells contiguous to
      neoplastic lesions also expressed bcl-2. These findings, along with down
      regulation of bcl-2 in differentiating carcinomas, suggest a role for this
      oncoprotein in relatively early stages of oral tumor progression. Differentiating
      neoplastic cells with marginal or no bcl-2 reactivity showed heterogeneous cell
      labeling of varying intensity for differentiation-associated cytokeratin (CK13),
      indicating their inverse topographic relationship.

PMID- 9638704
TI  - Cell population changes during atrophy and regeneration of rat parotid gland.
AB  - Limited data exist regarding the changes in number and location of myoepithelial
      cells during salivary gland atrophy and regeneration. Through the use of double
      immunohistochemical labeling for muscle-specific actin and amylase coupled with
      morphometric analysis, this study investigated the changes in distribution and
      proportion of cell types during salivary gland atrophy/regeneration phases in a
      model previously used to study proliferation in rat parotid gland. The double
      immunohistochemical labeling clearly showed the changes in proportion of cell
      types in the atrophying and regenerating glands. The morphometric analysis showed
      that the relative myoepithelial area increased (as did the intercalated duct and
      striated duct areas) as the gland atrophied. Myoepithelial cells occupied 19.0%
      of the total epithelial area by day 7 of atrophy, up from 2.7% in the resting
      gland. Regeneration of acinar cells was obvious 1 day after duct release. The
      myoepithelial cell area decreased to 4.3% of the total epithelial area by day 14
      of regeneration; this value was higher than the percentage of area in the resting
      gland (p = 0.02). The relative areas of acinar, striated duct, and intercalated
      duct cells returned to resting levels after 14 days of regeneration. The
      morphometric and histologic results of this study show that the parotid gland is
      capable of regenerating to essentially normal anatomic condition after 7 days of
      gland atrophy and then 14 days of regeneration. Each type of cell, however,
      responded to the atrophy and regeneration differently. Atrophy of salivary glands
      from radiation therapy. Sjogren's syndrome, or sialadenitis is an important
      clinical problem. Study of the salivary gland response to atrophy and
      regeneration may provide a framework for designing strategies for the
      radioprotection of salivary glands or methods by which to treat or reverse the
      effects of gland atrophy.

PMID- 9638705
TI  - Florid cemento-osseous dysplasia: Report of a case documented with computed
      tomography and 3D imaging.
AB  - Florid cemento-osseous dysplasia is an uncommon disease of the jaws. This article
      reports the case of a 49-year-old black woman who was diagnosed with florid
      cemento-osseous dysplasia on the basis of conventional radiographic findings.
      Computed tomography and three-dimensional imaging of the mandible were performed,
      and they enabled detailed localization of the bone defects. The role of computed
      tomography in the evaluation of cemento-osseous lesions is discussed.

PMID- 9638706
TI  - Pulp reaction to a tri-cure resin-modified glass ionomer.
AB  - OBJECTIVE: This study evaluated the pulp response to a tri-cure resin-modified
      glass ionomer cement and compared this response to those elicited by a zinc oxide
      eugenol cement and a silicate cement. Materials were placed in nonexposed class V
      cavity preparations on human teeth. STUDY DESIGN: Sixty premolars were selected
      in orthodontic patients in a voluntary group of teenagers. All cavities were
      prepared according to International Dental Federation specifications. Resin
      modified glass ionomer and silicate applications were carried out according to
      the manufacturers' instructions. RESULT: All teeth were asymptomatic. Pulp
      responses to the resin-modified glass ionomer cement were slightly greater than
      to the zinc-oxide-eugenol cement. Bacterial staining attempts were inconclusive
      with regard to time intervals and pulp responses. No necrotic pulps were seen in
      any teeth. CONCLUSION: The tri-cure resin-modified glass ionomer cement elicited
      a slightly greater adverse pulp response than did the zinc-oxide-eugenol cement
      with respect to the healing process of the pulp.

PMID- 9638707
TI  - Development of periradicular lesions in immunosuppressed rats.
AB  - PROBLEM: The role of bacteria has been well established in pulpal and periapical
      diseases, but the contribution of the host defenses is less clear. OBJECTIVES:
      The purpose of this study was to compare periradicular lesion development in
      immunosuppressed rats with that in normal rats. STUDY DESIGN: Fifteen rats were
      given weekly injections of Cytoxan (Bristol Laboratories) to suppress their
      immune systems. The pulps of mandibular first molars of these animals and another
      15 rats that had received no medications were exposed and left open to their oral
      flora. The rats were killed at 2, 4, and 6 weeks. Radiographic analysis was
      performed by means of a computer linked to a digitizing board and stylus. In
      addition, specimens were decalcified, sectioned, stained, and examined under a
      microscope with a grid to quantify relative percentages of surface areas of bone,
      root, periodontal ligament, marrow spaces, soft tissue, and inflammatory
      infiltrate. RESULTS: Statistical analysis showed a significantly greater
      radiographic bone loss in the immunosuppressed group only at 4 weeks. No
      significant histologic differences were found between the two groups. CONCLUSION:
      Our results suggest that reduction of circulating leukocytes may not
      significantly affect the development of periradicular pathosis in rats.

PMID- 9638708
TI  - Labial and palatal "talon cusps" on the same tooth: A case report.
AB  - Talon cusps are uncommon. Although they normally occur on the palatal surface of
      maxillary incisors, the literature contains two case reports of labial talon
      cusps. This is the first report describing a tooth with both a labial and a
      palatal talon cusp and its successful management.

PMID- 9638709
TI  - A diagnostic comparison of panoramic and intraoral radiographs.
AB  - OBJECTIVE: This study compared panoramic and intraoral radiographic surveys in
      the evaluation of specific dental pathoses in Air Force personnel. STUDY DESIGN:
      The radiographs of 30 subjects were read singly and in various combinations:
      panoramic survey only; periapicals plus bitewings; panoramic survey plus
      bitewings; and panoramic survey plus periapicals plus bitewings. Three
      independent, blinded examiners using standardized viewing conditions assessed the
      radiographs in random order for the presence of caries, periapical pathoses, bone
      loss, furcation involvement, impacted/unerupted teeth, internal/external root
      resorption, and retained roots. The consensus radiographic standard of true
      pathosis was the simultaneous interpretation by the three examiners of all
      radiographs for each subject. RESULTS AND CONCLUSIONS: The panoramic survey by
      itself was shown to have the lowest correlation with the consensus radiographic
      standard when basic military trainees with generalized dental pathoses were
      evaluated. The combination of panoramic survey plus bitewing radiographs
      exhibited a diagnostic yield for specific pathoses that was comparable to that of
      panoramic survey plus bitewings plus periapicals.

PMID- 9638710
TI  - Distribution of scattered radiation during intraoral radiography with the patient
      in supine position.
AB  - OBJECTIVE: The purpose of this study was to investigate the spatial distribution
      of scattered radiation during intraoral radiography with the patient in a supine
      position to determine the exposure to an operator without a suitable barrier.
      STUDY DESIGN: A phantom was placed in the supine position on a dental chair with
      the occlusal plane perpendicular to the floor, and four intraoral periapical
      radiographic examinations in the anterior and posterior regions of the maxilla
      and mandible were performed. The scattered radiation was measured with an
      ionization chamber at distances ranging from 25 to 200 cm at 25 cm increments and
      at intervals of 45 degrees. Measurements were made at two different heights:
      level with the occlusal plane and 30 cm below it. The exposure was converted to
      an air-kerma/absorbed dose in air. RESULTS: The distribution of scattered
      radiation was symmetric during examinations of the anterior region. Circular iso
      exposure curves of up to 0.5 microGy were observed at the level of the occlusal
      plane, and curves of up to 0.1 microGy were observed 30 cm below the plane. The
      lowest exposures were measured 30 cm below the occlusal plane and behind the
      chair. The distribution of scattered radiation was not symmetric during
      examinations of the posterior region. Iso-exposure curves of up to 0.25 microGy
      were observed at the level of the occlusal plane during exposure of the maxilla,
      and curves of up to 0.5 microGy were observed during exposure of the mandible.
      Circular iso-exposure curves of up to 0.1 microGy were observed 30 cm below the
      occlusal plane. Lower values for scattered radiation were observed 30 cm below
      the occlusal plane between 135 and 180 degrees behind the phantom. CONCLUSION:
      The spatial distribution of scattered radiation with the patient in a supine
      position was not the same in eight directions around the chair. Although the
      preferred position for the operator is behind a suitable barrier, the preferred
      position in the absence of a barrier is 200 cm behind the patient.

PMID- 9638711
TI  - The lesions of the pterygopalatine and infratemporal spaces: Computed tomography
      evaluation.
AB  - OBJECTIVE: The purpose of this study was to categorize the computed tomography
      features of lesions affecting the pterygopalatine fossa and infratemporal fossa
      and thus aid in the diagnosis of these lesions. DESIGN: Eighty-six patients with
      lesions of the pterygopalatine fossa and infratemporal fossa were examined with
      computed tomography; the lesions were confirmed by both surgery and biopsy. The
      patients were divided into three groups: group I consisted of patients in whom
      the lesions had originated in one or both fossae; group II, of patients in whom
      the lesions originated in other oral and maxillofacial regions but showed
      extension into the pterygopalatine and infratemporal fossae; and group III, of
      patients in whom the lesions had multicentric origins. RESULTS: Of the 11 cases
      in group I, demarcation was confined to both fossae in 4 patients, and
      involvement of the adjacent structures was shown on computed tomography images in
      7 patients. Involved structures included the maxillary sinus (4 sides), nasal
      cavity (3 sides), mandibular ramus (6 sides), buccal space (2 sides), base of the
      skull (5 sides), palate (3 sides), and parapharyngeal space (5 sides). In the 70
      cases in group II, computed tomography images showed that lesions had invaded
      both fossae via following routes: (1) 40 lesions in the maxillary sinus had
      infiltrated posterolaterally into 26 pterygopalatine and 39 infratemporal fossae;
      (2) two nasal cavity and three nasopharynx tumors had infiltrated laterally or
      lateroanteriorly into five pterygopalatine and one infratemporal fossae; (3)
      lesions originating in mandibular rami (9 lesions), buccal regions (4 lesions),
      parapharyngeal spaces (1 lesion) and parotid glands (1 lesion) had intruded
      medially into 15 infratemporal fossae; (4) two temporal bone tumors had
      encroached inferiorly on two infratemporal fossae; (5) four palate tumors had led
      to involvement of three pterygopalatine and four infratemporal fossae; and (6)
      four inflammatory diseases of the facial spaces involved two pterygopalatine and
      four infratemporal fossae. Group III lesions (5 cases) affecting one
      pterygopalatine and five infratemporal fossae were hemangiomas; one was a
      malignant lymphoma. CONCLUSION: Group I lesions may involve the adjacent anatomic
      structures of both pterygopalatine and infratemporal fossae in every direction.
      Group II lesions that correspond to the various origins of the maxillofacial
      region have different pathways of infiltration into the pterygopalatine or
      infratemporal fossae. Computed tomography examination is very important in the
      evaluation of lesions involving the pterygopalatine and infratemporal fossae.

PMID- 9638712
TI  - Can an oxygenator design potentially contribute to air embolism in
      cardiopulmonary bypass? A novel method for the determination of the air removal
      capabilities of neonatal membrane oxygenators.
AB  - At present, air handling of a membrane oxygenator is generally studied by using
      an ultrasonic sound bubble counter. However, this is not a quantitative method
      and it does not give any information on where air was entrapped in the oxygenator
      and if it eventually was removed through the membrane for gas exchange. The study
      presented here gives a novel technique for the determination of the air-handling
      characteristics of a membrane oxygenator. The study aimed at defining not only
      the amount of air released by the oxygenator, but also the amount of air trapped
      within the oxygenator and/or removed through the gas exchange membrane. Two
      neonatal membrane oxygenators without the use of an arterial filter were
      investigated: the Polystan Microsafe and the Dideco Lilliput. Although the air
      trap function of both oxygenators when challenged with a bolus of air was
      similar, the Microsafe obtained this effect mainly by capturing the air in the
      heat exchanger compartment while the Lilliput did remove a large amount of air
      through the membrane. In conclusion, the difference in trap function was most
      striking during continuous infusion of air. Immediate contact with a microporous
      membrane, avoidance of high velocities within the oxygenator, pressure drop,
      transit time and construction of the fibre mat all contribute to the air-handling
      characteristics of a membrane oxygenator.

PMID- 9638714
TI  - The effects of haemofiltration on cefazolin levels during cardiopulmonary bypass.
AB  - Ultrafiltration has been shown to affect cardiac drug concentrations during
      cardiopulmonary bypass (CPB), based on their respective pharmacological
      properties. In an attempt to understand the aetiology of sternal wound
      infections, a study was performed to eliminate the use of ultrafiltration as a
      possible cause. We compared cefazolin levels at three time intervals during the
      course of routine CPB with ultrafiltration to those levels in a control group in
      which ultrafiltration was not used. Our results indicate that there is little
      difference in the rate of decay of antibiotic levels with or without the use of a
      haemoconcentrator. This implies that ultrafiltration procedures do not put the
      patient at any increased risk for infection and that additional measures beyond
      that which we would normally use at our institution need not be taken.

PMID- 9638713
TI  - Clinical evaluation of a new generation membrane oxygenator: a prospective
      randomized study.
AB  - A new generation hollow-fibre membrane oxygenator (Spiral Gold) has been
      introduced by Baxter Healthcare (Irvine, CA, USA). The purpose of this study was
      to evaluate the operational performance of this device under clinical conditions
      and to compare it to the Univox Gold membrane oxygenator. Following institutional
      review board approval, and the obtainment of informed consent, 26 patients
      undergoing coronary artery bypass grafting were randomly assigned to either a
      Spiral Gold (Spiral) (n = 13) or Univox Gold (Univox) (n = 13) group. Study
      parameters were grouped into the following categories: haematological,
      haemodynamic, oxygenator performance and perioperative outcomes. All patients
      received identical surgical, anaesthesia and postoperative care. There were no
      statistically significant differences in either preoperative or operative
      parameters between groups. During cardiopulmonary bypass, the Spiral group had a
      significantly lower pressure drop (26.9 +/- 8.2 vs 46.7 +/- 16.2 mmHg, p <
      0.001). The Spiral group had significantly lower plasma free haemoglobin levels
      during all time periods of CPB compared to the Univox group. Heat exchange
      coefficients were higher during the rewarming period in the Spiral patients (0.59
      +/- 0.28) compared to the Univox group (0.36 +/- 0.19), p = 0.06. There were no
      differences in oxygen transfer between groups, but ventilation gas sweep rates
      and FiO2 levels were statistically lower in the Spiral group at two of the three
      sampling time periods. The ratio of ventilating gas sweep rate to blood flow rate
      was lower in the Spiral group (0.56 +/- 0.12) compared to the Univox group (0.74
      +/- 0.23), p < 0.03. The Spiral Gold oxygenator had superior oxygen transfer
      efficiency and lower haemolysis rates than the Univox Gold oxygenator.

PMID- 9638715
TI  - The influence of mannitol on renal function during and after open-heart surgery.
AB  - Mannitol is often included in the priming solution of the heart-lung machine used
      during cardiopulmonary bypass (CPB). This study was set up to evaluate the effect
      of different doses of mannitol on human patients. Patients receiving 10 g of
      mannitol (n = 18) had an increased diuresis only during the bypass period (mean
      time = 87 min) when compared with a control group (n = 19) who did not receive
      mannitol. Patients receiving 20 g of mannitol (n = 19) had a significantly
      greater diuresis than both the control group and the 10 g group and the diuresis
      continued on throughout the immediate postbypass period (total mean time
      approximately 3 h). Patients receiving 30 g of mannitol (n = 20) also had a
      significantly greater diuresis that continued on during the first hour in the
      intensive care unit (ICU) (total mean time approximately 4 h). After 6 h in the
      ICU, all three groups of mannitol-treated patients equally demonstrated a trend
      towards an increased diuresis over the control group, which became a significant
      increase by 12 h in the ICU (p = 0.001) despite indications that the mannitol had
      been cleared from the body. These results suggest that there is an improvement of
      renal function post-CPB if mannitol is included in the CPB prime which may be due
      to an amelioration of the ischaemic effects of bypass on the kidneys.

PMID- 9638716
TI  - The effect of albumin priming solution on platelet activation during experimental
      long-term perfusion.
AB  - The objective of this study was to evaluate the effect of albumin priming on
      platelet consumption and activation during long-term perfusion. Two identical in
      vitro extracorporeal membrane oxygenation circuits were used; one was primed with
      Ringer's solution containing human serum albumin, the other with Ringer's
      solution only. Fresh heparinized human blood was pooled, divided between the two
      systems and circulated for 24 h at 37 degrees C. Platelet count, plasma
      concentration of betathromboglobulin (BTG), platelet membrane density of
      glycoprotein (GP) Ib and of GPIIb/IIIa were assayed before the start and at 0.5,
      1, 3, 12 and 24 h of perfusion. In total, seven experiments were performed. We
      found that during the first hour of perfusion, slightly higher platelet counts (p
      = 0.058) and lower BTG values (p = 0.0005) were observed in the circuits primed
      with albumin, compared to the control circuits. No statistically significant
      differences were observed for the platelet membrane expression of GPIb and
      GPIIb/IIIa. We conclude that albumin priming appears to transiently prevent
      platelet consumption and activation during long-term perfusion.

PMID- 9638717
TI  - Heparin-bonded circuits: clinical outcomes and costs.
AB  - The aim of this study was to use meta-analysis to combine the results of numerous
      studies and examine the impact of heparin-bonded circuits on clinical outcomes
      and the resulting costs. Heparin-bonded circuits, both ionically and covalently
      bonded, are examined separately. The results of the study provide evidence that
      heparin-bonded circuits result in improved clinical outcomes when compared to the
      identical nonheparin-bonded circuits. These improved clinical outcomes result in
      subsequent lower costs per patient with their use. However, differences are
      apparent in the significance and magnitude of these outcomes between ionically
      and covalently bonded circuits. Covalently bonded circuits provide a greater
      magnitude and significance of improvement in clinical outcomes than ionically
      bonded circuits. Total cost savings can be expected to be three times greater
      with covalently bonded circuits ($3231 versus $1068). It was concluded that the
      choice regarding the use of a heparin-bonded circuits and the type of heparin
      bonded circuit used has the potential to alter clinical outcomes and subsequent
      costs. Cost consideration cannot be ignored, but clinical benefits should be the
      main rationale for the choice of cardiopulmonary bypass circuit. This analysis
      provides evidence that clinical benefits and cost savings can both be derived
      from use of the same technology-covalently bonded circuits.

PMID- 9638718
TI  - Clinical evaluation of a leucocyte-depleting blood cardioplegia filter (BC1B) for
      elective open-heart surgery.
AB  - Activation of leucocytes during extracorporeal circulation has attracted
      attention in recent years as a cause of reperfusion injury in open-heart surgery
      patients. In the present study, 40 adult patients undergoing elective open-heart
      surgery were randomized into two groups: 20 using the Pall BC1B leucocyte
      depleting filter for blood cardioplegia (group 1) and the other 20 without the
      filter (group 2). In order to determine if the filter was effective in protecting
      the myocardium, CPK-MB and troponin-T (TnT) were measured. In addition, efforts
      were also made to determine appropriate sites at which the BC1B blood
      cardioplegia filter should be positioned. There were no significant differences
      between the two groups in terms of conditions of perfusion. No adverse effects
      were seen in either group. The total leucocyte reduction rate through the filter
      was 98.1% with the passage of 2 liters of blood through the filter. A pressure
      drop of 4.4 +/- 3.2 mmHg was observed through the filter during use.
      Statistically significant differences were noted between the two groups in CPK-MB
      (p = 0.031) and TnT (p = 0.004). Findings obtained in previous studies
      demonstrate that the various advantages of leucocyte reduction, shown in
      experimental studies, can be translated into clinical advantages. In conclusion,
      based on the results in this clinical study showing significant difference in CPK
      MB and TnT which are known effective indicators for myocardial injury, between
      leucoreduced and non-leucoreduced group, the Pall BC1B leucocyte-depleting filter
      for blood cardioplegia has been shown to be effective in alleviating reperfusion
      injury in open-heart surgery patients.

PMID- 9638719
TI  - Extracorporeal membrane oxygenation in emergency resuscitation from deep
      hypothermia.

PMID- 9638721
TI  - Management of the erythropoietic porphyrias.

PMID- 9638720
TI  - Stockert roller pump generated pulsatile flow: cerebral metabolic changes in
      adult cardiopulmonary bypass.

PMID- 9638722
TI  - The porphyrias: an introduction.

PMID- 9638723
TI  - Management of the acute porphyrias.
AB  - Three hepatic porphyrias--acute intermittent porphyria, hereditary coproporphyria
      and variegate porphyria--are characterized by episodic acute attacks that consist
      of various neuro-psychiatric symptoms and signs, such as abdominal pain,
      vomiting, constipation, hypertension and tachycardia associated with increased
      excretion of porphyrins and porphyrin precursors. Peripheral neuropathy is
      manifested as pain in the extremities, and it may progress to a severe motor
      neuropathy. Measurement of porphobilinogen in the urine gives a prompt diagnosis
      during acute attacks. Attacks are often induced by precipitating factors such as
      drugs, alcohol, infection, fasting or changes in sex-hormone balance, and they
      should be eliminated when a patient is treated during an attack. Heme, the end
      biosynthetic product, is the most effective therapy for restoration of porphyrin
      biosynthesis to normal, and it is usually infused at 3 mg/kg daily for 4 days.
      Adequate calories are necessary and parenteral nutrition with carbohydrates may
      be necessary. Attacks may also require therapy for hypertension, pain and
      epileptic seizures. Strict avoidance of all precipitating factors may not be
      necessary in the asymptomatic phase.

PMID- 9638724
TI  - Hepatic complications of erythropoietic protoporphyria.
AB  - A quarter of patients with erythropoietic protoporphyria develop mild to severe
      cholestatic liver disease. The determination of early indicators of hepatobiliary
      involvement are of pivotal importance to select patients for choleretic therapy.
      Porphyrin parameters were studied during ursodeoxycholic acid treatment in eight
      patients with protoporphyrin-associated liver disease and eight patients with
      liver failure before and after liver transplantation. The patients with
      intrahepatic cholestasis exhibited excessive protoporphyrinemia (27 mumol/l)
      compared with controls (normal < 0.64 mumol/l). Fecal protoporphyrin excretion
      decreased in patients with deterioration of liver function, whereas urinary
      coproporphyrin increased up to 2290 nmol/24 h (normal < 119 nmol/24 h).
      Coproporphyrin isomer I proportion increased to 71 +/- 10% (mean +/- SD, n = 8)
      in patients with terminal liver failure (normal < 31%). During therapy with
      ursodeoxycholic acid biochemical improvement occurred but without clinical
      remission in most cases. Eight patients underwent liver transplantation between
      1987 and 1997. One patient died of liver failure. Two transplant recipients are
      in a good condition since 8 and 9 years, respectively. All explanted livers
      revealed micronodular cirrhosis and high protoporphyrin levels of about 25,000
      fold (mean, n = 3). Immediately after liver transplantation protoporphyrin in
      erythrocytes decreased to 46-96% of pre-operative values. Coproporphyrin remained
      moderately elevated due to post-operative cholestasis. A post-operative rise in
      fecal protoporphyrin elimination reflected sufficient biliary clearence of
      protoporphyrin by the transplant. In conclusion, moderate coproporphyrinuria with
      isomer I is the earliest sign of liver complications in erythropoietic
      protoporphyria. Progression of protoporphyrin induced toxic liver injury is
      indicated by excessive protoporphyrinemia and coproporphyrinuria with an isomer I
      proportion > 71 +/- 10%, and reduction of fecal protoporphyrin excretion. Results
      suggest that therapy of intrahepatic cholestasis with ursodeoxycholic acid is
      only effective in the initial stages of liver disease in erythropoietic
      protoporphyria. In patients with severe cholestatic hepatic failure, liver
      transplantation is the treatment of choice.

PMID- 9638725
TI  - Evaluation of porphyria.

PMID- 9638726
TI  - Management of patients with porphyria cutanea tarda.

PMID- 9638727
TI  - Update on enzyme and molecular defects in porphyria.
AB  - Each porphyria results from decreased activity of one of the enzymes of haem
      biosynthesis. The molecular basis of enzyme deficiencies in acute intermittent
      porphyria (AIP), variegate porphyria (VP) and congenital erythropoietic porphyria
      (CEP) is outlined. All three conditions show extensive allelic heterogeneity. In
      the autosomal dominant disorders, AIP and VP, no genotype/phenotype correlations
      have been demonstrated, and the explanation for their low clinical penetrance
      remains uncertain. In AIP and VP, mutational analysis is superior to biochemical
      methods for screening families for latent porphyria. In the autosomal recessive
      condition, CEP, there is some genotype/phenotype correlation--one common mutation
      (C73R) being associated with severe disease in homozygotes. Porphyria cutanea
      tarda (PCT) is not a simple monogenic disorder. Patients appear to have an
      inherited susceptibility to inactivation of hepatic uroporphyrinogen
      decarboxylase (UROD) as part of a response to hepatocyte injury by alcohol, HCV
      and other agents. Inherited factors that, in combination, may predispose to PCT
      include mutations in the UROD gene, present in about 20% of patients, and the
      C282Y mutation in the haemochromatosis (HFE) gene.

PMID- 9638728
TI  - Molecular genetics of erythropoietic protoporphyria.
AB  - Erythropoietic protoporphyria (EPP) is caused by decreased activity of the enzyme
      ferrochelatase and is characterized by burning photosensitivity commencing in
      childhood. From 1-10% of patients develop potentially fatal protoporphyric
      hepatic failure. The gene for ferrochelatase has been cloned, sequenced and
      mapped to the long arm of chromosome 18. EPP is genetically very heterogeneous
      and 24 different mutations in 27 unrelated patients have been published. In the
      majority of families co-inheritance of a mutant ferrochelatase allele from one
      parent and a low-output "normal" ferrochelatase allele from the other parent is
      required for disease expression. The molecular basis, if any, of protoporphyric
      hepatic failure has not yet been resolved. Gene therapy experiments have been
      completed in vitro and are in progress in an animal model of EPP. In conclusion,
      molecular genetic investigation of EPP has increased our understanding of its
      pathogenesis and inheritance. Why some EPP patients develop hepatic failure is
      still unanswered. Gene therapy of EPP patients may become possible in the future.

PMID- 9638729
TI  - Skin pigmentation in Caucasian babies is high and evenly distributed throughout
      the body.
AB  - To investigate if Caucasian babies have particular sun sensitive skin and if skin
      pigmentation before any sun exposure is uniform throughout the body, we measured
      skin pigmentation objectively by skin reflectance spectroscopy in 10 anatomical
      sites in 20 healthy Caucasian babies (mean age 5 months, range 1 to 10 months)
      that had not been sun exposed previously. We found that skin pigmentation at all
      the measured sites was significantly higher than the constitutive pigmentation in
      Caucasian adults (P < 0.01). Furthermore, the level of skin pigmentation in all
      the 10 measured sites in the babies was statistically not different (P < 0.31)
      and there was no gender differences in pigmentation for any site.

PMID- 9638730
TI  - Two patients with isoniazid-induced photosensitive lichenoid eruptions confirmed
      by photopatch test.
AB  - Causative agents of drug eruptions are frequently unknown, and skin tests with
      candidate drugs would be useful before systemic challenge. It remains to be
      clarified how phostosentive lichenoid drug eruptions are induced, but allergy,
      including delayed type allergy, has been suggested. Two patients who had taken
      anti-tuberculous drugs developed a lichenoid drug eruption, primarily on sun
      exposed skin. Patch and photopatch tests were performed with each of the ingested
      drugs (10% in petrolatum). Photopatch tests to isoniazid (INH) were positive.
      These were confirmed by oral challenge followed by irradiation with UVA. In
      conclusion, photopatch tests facilitated identification of the causative drug in
      two patients with photosensitive lichenoid eruptions to INH.

PMID- 9638731
TI  - A hazard assessment of artificial tanning units.
AB  - As a result of increasing concern over the use of artificial tanning units, many
      local government recreation departments are phasing out the use of sunbeds on
      their premises, resulting in some clients switching to high street parlours about
      which little is known. An Environmental Health survey was conducted in all 32
      tanning premises within a local government area (Perth & Kinross, Scotland). A
      number of significant problems emerged in the private sector. In this group,
      there was no form of cumulative UV exposure control in 89% of premises and 81%
      failed to give adequate advice and information to customers. We conducted UV
      spectral irradiation measurements in 38 tanning units using a double grating
      spectroradiometer. When a carcinogenic weighting factor was applied to these
      measurements, it was found that a 10 min exposure in a high intensity stand-up
      cabinet carried the same carcinogenic risk as approximately 30 min of local (56
      degrees North) mid-day summer sunlight or 10 min of Mediterranean sunlight at mid
      day. A questionnaire completed by 57 customers revealed a wide pattern of usage;
      6 (10%) had more than 20 h exposure in the previous 12 months and 3 (5%) had made
      regular use of sunbeds for the previous 16 to 20 years. These results indicate
      that there is a need for continuing public education and surveillance of
      commercial artificial tanning units.

PMID- 9638732
TI  - Withdrawal of presession saccharin suppresses food-maintained responding in rats.
AB  - Decreased motivation following drug withdrawal is often characterized as
      indicative of addiction. Similar behavioral disruptions are seen in negative
      contrast paradigms. In the current study, 7 rats with a history of access to a
      palatable 0.15% saccharine solution before operant sessions were conditioned.
      Rats responded for food under a multiple FR 5 FR 40 reinforcement schedule. When
      presession saccharin was removed and replaced with water, responding maintained
      by food was significantly decreased, with greater effects observed under the FR
      40 schedule. These results support the assertion that behavioral disruptions
      accompanying withdrawal syndromes include a negative contrast component.

PMID- 9638733
TI  - Reliability estimates of the Purpose in Life and Seeking Noetic Goals tests with
      rural and metropolitan-area adolescents.
AB  - The Purpose in Life and Seeking Noetic Goals tests were administered to 198 rural
      Missouri and 659 metropolitan-area Washington high school students and
      readministered after an 8-week interval. The obtained test-retest and Cronbach
      alpha coefficients were largely consistent with earlier research using adult
      clinical samples.

PMID- 9638734
TI  - Performance on two attention tasks as a function of sex and competition.
AB  - Effects of sex and competition on receptive attention and Stroop task performance
      of 59 college students were investigated, 33 participants in a competitive
      condition were informed that performance would be ranked by sex; 36 in a
      noncompetitive condition were given no information regarding competition.
      Consistent with previous research, no significant main effects or interactions
      were found for scores on the receptive attention task. Contrary to previous
      findings, though, the Stroop task also yielded no significant main effects;
      however, a significant interaction was found. Men experienced more interference
      in the competitive condition, whereas women showed no significant effects of
      competition. Women did experience more interference than men in the
      Noncompetitive condition. Conclusions suggest that men may be more sensitive to
      sex-based performance comparisons.

PMID- 9638736
TI  - Semantic activation by Japanese kanji: evidence from event-related potentials.
AB  - In a character-judgment paradigm, the subject quickly pressed a key when a
      hiragana (Japanese syllabary) appeared on a display and did nothing when a kanji
      (Japanese logograph) appeared. The amplitude of the N400 component was compared
      when four types of visual stimuli were used: (Type 1) single kanji--Grade 1- to 3
      level words, (Type 2) single kanji--Grade 1- to 3-level bound morphemes, (Type 3)
      single kanji--high school- and college-level bound morphemes, and (Type 4)
      obsolete kanji. Analysis showed that N400 was largest in the temporal-occipital
      areas for the Type 1 stimuli and larger in the right parietal area for Type 2
      than Type 3 stimuli. The analyses of N400 to semantic stimulations have been
      conducted and discussed in terms of their meaningfulness, age when writing of
      these kanji was mastered, and linguistic status (kanji versus nonkanji). Most
      interestingly, the Types 3 and 4 kanji did not activate semantic responses,
      showing that they did not function as linguistic units, i.e., kanji, in the
      mental lexicon.

PMID- 9638737
TI  - Indirect tactual discrimination of heights by blind and blindfolded sighted
      subjects.
AB  - The ability of blind and blindfolded sighted subjects to discriminate cubes of
      different heights was measured using the method of constant stimuli. Five male
      blind and 5 male blindfolded sighted students, ages 22 to 28 years, were
      subjects. All blind subjects had undergone orientation and mobility training at a
      school for the blind. The cubes, made of wood, were explored using a long cane.
      Subjects were presented the standard cube and a comparison cube and required to
      judge whether the comparison cube height was taller, the same, or shorter than
      the standard. Analysis showed that the difference thresholds of blind and
      blindfolded sighted subjects were 1.93 and 2.14 cm, respectively. No significant
      difference in accuracy of discrimination was found between the two groups. The
      blind subjects showed significantly better performance than the blindfolded
      sighted subjects on the discrimination task. The blind subjects performed the
      task significantly faster than the blindfolded sighted subjects. The results
      suggest that braille reading, use of a long cane, and daily physical activities
      which required prolonged haptic or proprioceptive learning, may enhance nonvisual
      motor skills.

PMID- 9638738
TI  - Methodological concerns when using silhouettes to measure body image.
AB  - This paper discusses methodological concerns of using silhouette figures to
      measure body images. These include concerns related to scale coarseness (limiting
      response options to one of a finite number of drawings), restriction of range,
      method of presentation, and scale of measurement. Recommendations are made to
      address these limitations, and an alternative silhouette scale using continuous
      scale measurements is proposed.

PMID- 9638739
TI  - Spacing effects on implicit picture memory.
AB  - 25 undergraduates studied the stimulus pictures of common objects successively
      presented as spaced or massed repetitions, or one at a time. Immediately after a
      study period, they were given a free-recall test followed by a perceptual
      identification test. Analysis indicated that spacing effects were observed on the
      free-recall test but not in perceptual identification. On the later test, each
      stimulus picture was exposed for a short period and subjects were more likely to
      use perceptual cues than on first the test. Thus, the spacing effects on memory
      may be eliminated at test as there is no benefit of conceptual cues.

PMID- 9638740
TI  - Ear preference: association with other functional asymmetries of the ears.
AB  - The bases for the preferential use of one ear are not clear. We investigated ear
      preference, asymmetry on a dichotic listening test and acuity dominance
      (laterality of hearing loss) in a sample of 51 patients with mild high frequency
      hardness of hearing. There was a higher correlation between measured ear
      preference and the measured acuity dominance than between ear preference and
      dichotic listening, suggesting a certain peripheral (cochlear) base for the ear
      preference.

PMID- 9638741
TI  - Practice and serial reaction time of adolescents with autism.
AB  - This study examined effects of practice on timing of serial reactions by 7
      adolescents diagnosed with autism by using a task requiring they track a series
      of timed lights. The adolescents showed significantly slower and more variable
      mean simple reaction time than 10 normal control subjects of the same age. On a
      task of tracking a serial light stimulation for 4 days, on the other hand,
      significant effects of practice on timing of serial reactions were observed for
      mean serial reaction times of them. In addition, from individual variations in
      reaction times and anticipatory reaction times, four of seven subjects with
      autism showed significant effects of practice. Analysis suggested that these
      autistic adolescents may be chunking together the whole series of responses and
      are unable to coordinate the timing of individual responses with individual
      stimuli. Our data indicate that at least some adolescents with autism are able to
      form and utilise a motor program with practice.

PMID- 9638742
TI  - Body consciousness in Dohsa-hou, a Japanese psychorehabilitative program.
AB  - To seven cerebral palsied children in a special elementary school, Dohsa-hou, a
      Japanese psychorehabilitative program, was introduced in a pre-post design. With
      the help of their mothers in writing they rated on a 5-point scale changes in
      their body consciousness by applying 8 1-hr. sessions of Dohsa-hou training to
      each child. Analysis suggests a significant positive change after training in
      body consciousness of these children especially for private as compared to public
      body consciousness.

PMID- 9638743
TI  - Comparison of demands of sustained attentional events between public and private
      children's television programs.
AB  - The durations and variability of changing events were analyzed for 20 min. each
      of 13 children's television programs. These programs included selections from
      both publically and privately produced shows. Significantly different patterns of
      attentional demands were found between the programs. Public television
      programming is characterized by longer and more variable durations of sustained
      attentional events, while private television programming is best described as
      having fast-paced shorter events. The implications of this finding for
      difficulties in learning by school-age children to attend for longer periods are
      discussed.

PMID- 9638744
TI  - An examination of the reliability and validity of scores on the Italian version
      of the Dieter's Inventory of Eating Temptations.
AB  - The aim of this paper was to highlight some psychometric characteristics of
      scores on the Italian version of the Dieter's Inventory of Eating Temptations.
      The analysis included assessment of the internal consistency of the individual
      scales, test-retest reliability, and estimates of both convergent and
      discriminant validity. Analyses showed that the Italian version of the inventory
      can be considered reliable and valid, which suggested its use as screening test
      for the identification of subjects who may be at risk for over-eating.

PMID- 9638745
TI  - Differences in auditory scalp potentials evoked by meaningful words and
      nonlinguistic stimuli.
AB  - Differences in auditory evoked potentials with meaningful words and their reverse
      playback may reflect different neural processes in recognizing auditory stimuli.
      Auditory evoked potentials with the words and their reverse playback were
      analyzed for eight volunteers, and a maximal difference was observed at a latency
      around 400 msec. over the left middle temporal central area.

PMID- 9638746
TI  - Two measures of laterality in handedness: the Edinburgh Handedness Inventory and
      the Purdue Pegboard test of manual dexterity.
AB  - This study investigated the relationship between a paper-and-pencil measure of
      laterality in handedness, the Edinburgh Handedness Inventory, and a test of
      manual dexterity, the Purdue Pegboard test. Individuals of extreme handedness
      based on the Edinburgh Handedness Inventory (laterality Quotients of +90 to +100
      and -100 and +54; 50 each) were recruited to complete the Purdue Pegboard test of
      manual dexterity. Subjects in the sinistral group had significantly smaller mean
      discrepancy scores in performance between their hands [t80 = 5.12, p = .0001] and
      much greater variance in performance than dextral subjects (F1,98 = 2.85, p =
      .0001). These findings suggest that paper-and-pencil measures of lateral
      preference for handedness may not identify proficiency of subgroups within a
      sinistral group.

PMID- 9638747
TI  - Figure-ground perceptual organization and learning by three-year-old children.
AB  - We have elaborated a program for the instruction of 54 3-yr.-olds using visual
      aids (cards showing the graphic representation of a number printed on three
      different types of backgrounds). Analysis showed differences in the increase in
      scores obtained by the children before and after the application of the program
      depending on the type of background.

PMID- 9638748
TI  - Similar Muller-Lyer effects from operant and comparison response modes.
AB  - A one-sided (monopole) version of the Muller-Lyer was used to assess the effect
      of response mode on the metric distortion associated with the illusion. Two
      different response modes were tested for comparability. The Operant Mode required
      the judgment of stimulus span to be indicated by marking a dot on the test page.
      The Comparison Mode required judgment of equality of two adjoining prepositioned
      spans. The perceptual effects with the comparison procedure are known to consist
      of underestimation of spans which are bounded by concave fin-sets and over
      estimation of spans which are bounded by convex fin-sets. The question is whether
      the motor demands of the operant task produce an additional source of metric
      bias. Analysis indicate a very high correlation of judgments for the two modes of
      testing. Also, data with either mode of responding closely fit a linear model of
      the effect, and the model provides comparable index values for the concave and
      convex versions. These results should mitigate concern about potential motor bias
      from the operant method and encourage its use as a more efficient procedure for
      assessing metric distortion.

PMID- 9638749
TI  - Effect of music on spatial performance: a test of generality.
AB  - Previous attempts by various researchers to replicate the enhancement of spatial
      performance following 10 min. exposure to music have been inconsistent in their
      findings. In the present study 16 subjects showed reliable improvement on a paper
      folding-and-cutting task after listening to Mozart's Sonata for Two Pianos in D
      major, as employed by others. The enhanced performance was also noted for 16
      other subjects after listening to a contemporary selection having similar musical
      characteristics. In both cases the control procedure included 10 min. of
      listening to a progressive relaxation tape.

PMID- 9638750
TI  - Information-processing characteristics of explicit time estimation by patients
      with schizophrenia and normal controls.
AB  - The information-processing characteristics of time estimation have not been well
      documented. This research investigated explicit time estimation to test whether
      (1) it can occur "automatically" and (2) the cognitive function generally known
      as "working memory" predicts accuracy of time estimation. Data on two tasks
      requiring explicit time judgement (time interval estimation and production) are
      reported for a sample of 43 normal, healthy controls and 19 inpatients with
      chronic schizophrenia. Each task was given in a standard (passing time interval
      is unfilled) and dual-task format (interval is filled by oral reading).
      Multivariate analysis of variance suggested that for both patients' and the
      normal controls' time estimation accuracy was (1) highly sensitive to whether a
      passing interval was filled with a concurrent activity such as reading and (2)
      predictable on the basis of age, education, and working memory skills. Also, the
      effect of the dual-task manipulation did vary as a function of psychosis for the
      Time Interval Production task. The data suggest that procedures for explicit time
      judgements do not occur automatically and utilize controlled processes such as
      working memory.

PMID- 9638751
TI  - Mental rotation: a task for the assessment of visuospatial skills of children.
AB  - 7 girls and 5 boys, ranging in age from 7 to 12 years, participated in the pilot
      testing of a mental rotation task developed for use in a comprehensive test
      battery of visuoperceptual abilities. Two asymmetric, three-dimensional objects
      were constructed from wood strips such that one object was the mirror-image of
      the other. Black and white photographs were taken of these objects in various
      spatial orientations along a horizontal plane. 16 photographs depicted the object
      right-side-up and in 16 the object was upside-down (rotated 180 degrees in the
      vertical plane). These photographs were presented to the children who were asked
      to match each with the corresponding object. Analysis indicated correct
      judgements of the right-side-up images occurred more frequently than the upside
      down images (t11 = 4.73, p < .001). Using these data, adjustments were made to
      the task instructions to provide greater clarity for the young participants.

PMID- 9638753
TI  - Psychometric properties of the grade 4 reading level Multiple Affect Adjective
      Check List-Revised with offenders.
AB  - The reliability and validity of the Grade 4 reading level Multiple Affect
      Adjective Check List was assessed with offenders in four settings within the
      criminal justice system. With the exception of the Sensation Seeking Scale, the
      MAACL-R4 scales showed good internal consistency and test-retest reliability and
      adequate convergent and discriminant validity, but not for the Depression scale
      for 53 female arrestees and the Hostility scale with 51 male arrestees.
      Correlations with self-ratings of health and stress and with the Family
      Environment scales were in expected directions. It is concluded that the MAACL-R4
      has the basic qualities necessary for use in research with offenders.

PMID- 9638752
TI  - Unilateral neglect in children with hemiplegic cerebral palsy.
AB  - The purpose of this study was to examine the pattern of attentional deficits in
      children with right and left hemiplegic cerebral palsy. Unilateral neglect and
      visuospatial deficits are common findings following right brain injury in adults.
      It has been suggested by some that children may show a similar pattern. Children
      were tested on several paper-and-pencil measures of neglect. It was hypothesized
      that (a) on the left side of the page, children with left hemiplegia (right
      hemispheric damage) will score significantly lower than both the control group
      and the right hemiplegia group and (b) on the right side of the page, there will
      be no significant difference between the control group and the right and left
      hemiplegic groups. Participants included 32 children with cerebral palsy, 15 with
      left hemiplegia, 17 with right hemiplegia, and 32 matched controls. The ages
      ranged from 5 years 10 months to 12 years 6 months; all had normal intelligence.
      Inventories included 3 subtests of the Conventional part of the Behavioral
      Inattention Test, the Mesulam Symbol Cancellations tests, and the Rey Osterrieth
      Complex Figure, copy and recall. Analysis indicated that children with left
      hemiplegia scored significantly more poorly than controls on seven of the eight
      measures on the left side of the page, but they did not consistently score more
      poorly than children with right hemiplegia. Moreover, the poorer performance of
      the children with left hemiplegia was not specific only to the left side of the
      page; they also scored significantly lower than the controls on five of the eight
      measures on the right side. These findings suggest that children with left
      hemiplegia may have relatively greater attentional and perceptual problems than
      children with right hemiplegia, but they do not clearly indicate a left
      unilateral neglect. Results also indicate that children with right hemiplegia
      have attentional and perceptual problems relative to controls, particularly on
      the more complex tasks of high demand.

PMID- 9638754
TI  - Economic growth and suicide and homicide rates revisited.

PMID- 9638755
TI  - Congenital dyschromatopsia and school achievement.
AB  - In 1993-94, in Liguria (a northwestern Italian region) a study was carried out on
      dyschromatopsia, a congenital sex-linked form of colour blindness. 3124 junior
      high school boys aged 10-15 years were tested using Ishihara plates (1973
      edition) and Farnsworth's D-15 test (1947 edition). 152 students were identified
      as colour blind (4.87%), a value slightly below the Italian average of 5.3%. The
      school achievement of these students was assessed by means of the school marks of
      two randomised subsamples composed of 82 dyschromates and 82 orthochromates,
      paired homogeneously by age and class. Statistical analysis indicated
      significantly lower general school achievement for the 82 dyschromate subjects
      (except for art). The learning difficulties of dyschromate persons for whom
      colour is a basic didactic tool are discussed. Introduction of dyschromatopsia
      tests at preschool would be desirable.

PMID- 9638756
TI  - Physical exertion in simple reaction time and continuous attention of sport
      participants.
AB  - To investigate the effect of physical exertion on simple reaction time and
      continuous attention of sport participants, an experiment was conducted with 46
      male university students and 12 male cyclists. The subjects were assigned to
      three experimental and two control groups. The subjects of the experimental
      groups were asked to perform, following a 5-min, period of warming up, a high
      intensity exercise protocol for 5 min., on a mechanically braked cycle ergometer
      (Group A) or a moderate intensity exercise protocol for 30 min, on the same cycle
      ergometer (Groups B and C). Shortly before and immediately after the physical
      exercise subjects of all groups were asked to perform a test of simple reaction
      time and continuous attention. The subjects of the control groups were asked to
      perform at rest both tests of the simple reaction time and the continuous
      attention twice, with a 10-min. and a 35-min. interval between the first and
      second attempts, respectively. The results did not support the notion that
      exercise of moderate or high intensity influences significantly the cognitive
      performance of aerobically trained or untrained subjects. The results are
      discussed in the light of the current research findings concerning exertion and
      human psychomotor performance.

PMID- 9638757
TI  - Handwriting in assessing treatment for substance abuse.

PMID- 9638758
TI  - Identification of a speaker's sex: a study of vowels.
AB  - An experiment was carried out to test whether three phonetically naive listeners
      were able to identify a speaker's sex from brief natural vowel segments. All
      speech segments presented to the listeners were extracted from sentences spoken
      by members of a group of three women and three men with a British General
      Northern accent. Analysis showed that listeners were able to identify the
      speaker's sex from the vowel segments with high accuracy (a mean score of 98.9%,
      p < .001). Acoustic analyses were subsequently carried out to quantify the
      acoustic and phonetic differences related to the sex of the speakers. Fundamental
      frequencies and format frequencies of the vowel stimuli were investigated. The
      men generally had lower values of both than the women.

PMID- 9638759
TI  - Identification of a speaker's sex: a fricative study.
AB  - An experiment was carried out to test whether three phonetically naive listeners
      were able to identify the speaker's sex from brief (30 msec. to 100 msec.)
      voiceless fricative segments. All speech segments were extracted from sentences
      spoken by members of a group of 3 women and 3 men with a British General Northern
      accent. The consonant segments were significantly identified by the listeners
      with an accuracy of 64.4%. A sample of the fricative segments was chosen to
      investigate acoustic and phonetic differences related to a speaker's sex, using
      spectrographic analysis. Analysis showed that on the average the frication of the
      women's voiceless fricatives was significantly higher in frequency than that of
      the men.

PMID- 9638760
TI  - Influence of time of day on anaerobic capacity.
AB  - 12 volunteers performed exhaustive exercise tests in the morning and afternoon.
      Paired-means t tests indicated that anaerobic capacity, as reflected by maximal
      accumulated oxygen deficit, was 26% higher (p < .01) in the afternoon than in the
      morning. VO2max appeared higher and VO2 kinetics seemed faster in the afternoon,
      but differences did not attain statistical significance. Thus, the time of day
      affects anaerobic capacity and may influence other responses to exercise.

PMID- 9638761
TI  - Effectiveness of redundant color coding in multidimensional identification.
AB  - This study investigated the effectiveness of redundant color coding in
      multidimensional identification. Statistical analysis showed that redundant color
      in multidimensional identification did not necessarily improve performance and
      response speed might even deteriorate if subjects were not informed of the use of
      redundant color. Merely informing subjects of the use of redundant color might
      not benefit identification speed either; subjects had to actually use color in
      responding to facilitate response speed. Further, redundant color might be more
      appropriate to associate with the less-salient or the less-familiar stimulus
      attribute. Implications of the results for the design of multidimensional display
      and for human information processing were discussed.

PMID- 9638762
TI  - Adolescents' perceptions of psychosocial factors related to sickle cell disease.
AB  - 12 adolescents with sickle cell disease rated psychosocial reactions to their
      disease. They had positive social and family relationships but had concerns about
      body development, self-confidence, being a burden on their families, and death.

PMID- 9638763
TI  - Preliminary development of a scale to measure attitudes regarding the importance
      of role modeling in physical activity and fitness behaviors among Health,
      Physical Education, Recreation, and Dance professionals.
AB  - This paper presents a new 16-item scale designed to measure attitudes regarding
      the importance of role modeling in physical activity and fitness behaviors among
      Health, Physical Education, Recreation, and Dance professionals. The measure was
      reviewed for face validity by a panel of experts and preliminary analyses gave as
      Cronbach alpha of .95 and split-half reliability of .97 for 22 graduate students.

PMID- 9638764
TI  - Speakers' sex differences in voice onset time: a study of isolated word
      production.
AB  - This report presents a brief study into sex differences of speakers in the voice
      onset time of English plosives that are stressed in both word-initial and
      prevocalic positions. 36 isolated words were spoken by 5 men (age range 25 to 37
      yr., M: 34.2 yr.) and 5 women speakers (age range 28 to 38 yr., M: 32.6 yr.) who
      were subjects. Analysis showed that the women speakers had on the average
      relative to the men, longer voice onset time values for voiceless plosives and
      shorter voice onset time values for the voiced plosives.

PMID- 9638765
TI  - Comparison of the vertec and Just Jump Systems for measuring height of vertical
      jump by young children.
AB  - To assess differences between the Vertec and the Just Jump Systems in measuring
      height of vertical jump, 248 boys and 232 girls between 7 and 11 years were
      required to perform four maximal countermovement vertical jumps. A maximum of the
      four trials recorded was the dependent variable. Each vertical jump was
      simultaneously evaluated by each measuring device and a paired t test indicated
      the systems were significantly different; however, the experiment wise difference
      of .93 in has no practical value. The Just Jump System seems a viable
      alternative. Advantages and potential pitfalls regarding the use of each system
      are discussed.

PMID- 9638766
TI  - Correlations between hand preference and durations of hearing for right and left
      ears in young healthy subjects.
AB  - In this study, to test an inference from the 1991 Previc hypothesis that right
      handers have a right-ear advantage, the durations of hearing for the right and
      left ears were compared for 81 right- and 45 left-handed high school students. In
      the present study, right-handedness was associated with a right-ear advantage and
      left-handedness was associated with a left-ear advantage. In addition, there was
      a significant positive correlation between the durations of hearing for the right
      and left ears and the scores for right-handedness for right-handed subjects. The
      durations of hearing for the right and left ears were negatively correlated with
      the left-handedness for left-handed subjects. These results suggest hand
      preference may be related to asymmetry of aural sensitivity.

PMID- 9638767
TI  - Education students' description of learning 'disabilities'.
AB  - 295 first- and fourth-year students in the College of Education at the University
      of Saskatchewan, Canada were asked to describe learning disabilities. When the
      descriptors they used were categorized, nonparticipation in the classroom formed
      the largest single category.

PMID- 9638768
TI  - Sports members' participation in assessment of incidence rate of injuries in five
      sports from records of hospital-based clinical treatment.
AB  - This study is about the incidence rate of sports injuries in five different types
      of sports, gymnastics, soccer, volleyball, hockey, and basketball, for which
      5,154 patients were admitted to the Emergency Unit of the Groningen University
      Hospital during the period 1990 through 1994. Incidence rate had been computed by
      membership participation. Basketball had the highest incidence rate (231 injured
      persons per 10,000 participants), followed by hockey (158 injured persons per
      10,000 participants). The highest mean Injury Severity Score, 2.39, was found for
      gymnastics which had the lowest incidence rate (7 injured persons per 10,000
      participants). Gymnastics had the highest percentage (12%) clinically treated
      patients, whereas basketball had the smallest percentage (2%) of clinically
      treated patients. The most frequent type of injury was distorsion, except for
      hockey, in which contusion had the highest percentage of occurrence. For all five
      types of sports, the majority (about 90%) of the injuries were observed at either
      the lower or at the upper extremities.

PMID- 9638769
TI  - Redundancy gain in discrimination of colored lights: effects of complexity and
      eccentricity.
AB  - The present study investigated the redundancy gain in discrimination of colored
      lights. Subjects were requested to discriminate a target from 34 nontarget lights
      differing from the target in luminance, hue, or both, and RTs were recorded.
      Experimental variables were the complexity of stimulus pattern and the
      eccentricity of the target in visual angle. The 35 lights were arranged regularly
      on an imaginary grid in the low-complexity condition and were arranged randomly
      in the high-complexity condition. The eccentricity of target was varied from 0
      degree to 16 degrees. Only when the stimulus pattern was highly complex and
      eccentricity was large, the combination of luminance and hue made the subject's
      discrimination faster than when luminance or hue individually operated as a cue
      for discrimination. That is, a redundant target effect was found only for a
      highly complex stimulus pattern and in peripheral vision.

PMID- 9638770
TI  - Novelty and complexity in human infants' exploratory behaviour.
AB  - The effect of novel and complex stimulus cubes on the exploratory behaviour of
      human infants was analysed in two studies (ns = 30 and 20). Infants showed
      relatively greater preference for complex patterned cubes, and their exploratory
      behaviour habituated over 5 days.

PMID- 9638771
TI  - Attitudes of undergraduate physical education majors in Brazil toward teaching
      students with disabilities.
AB  - This study assessed the relationship of attitudes of physical education majors in
      Brazil to specific disabling conditions, i.e., Emotional and Behavioral
      Disorders, Specific Learning Disabilities, Moderate Mental Retardation, and
      Orthopedic Impairment. This study also identified which selected teachers'
      attributes, i.e., age, sex, years of teaching, course work in adapted physical
      education, course work in special education, years teaching students with
      disabilities, quality of teaching experience, and perceived competence were
      related to favorable attitudes. Analysis showed no significant differences toward
      teaching students with these disabilities. Simultaneous multiple regression
      procedure also showed perceived competence was the only statistically significant
      predictor of attitudes toward teaching such students.

PMID- 9638772
TI  - A signal-detection theory based perspective on design of warning.
AB  - The effects of warnings are analyzed using a distributed signal-detection theory
      model. It is established that selectivity always increases effectiveness. The
      implications to optimal warning design for intermittent versus continuous hazards
      are discussed. The changes in the behavior of the 6 human subjects in response to
      changes in the warning levels are consistent with the predictions of the model.

PMID- 9638773
TI  - Sex differences in exercise motivation and body-image satisfaction among college
      students.
AB  - The current study was an expansion of one by Cash, Novy, and Grant in 1994, in
      which responses of 101 female nursing students were examined for associations
      between reasons for exercise, frequency of exercise, and body-image satisfaction.
      In the current study, 78 male and 100 female undergraduates between the ages of
      18 and 25 years (M = 21.2, SD = 1.9) from various majors completed a
      demographics/frequency of exercise survey, two body-assessment inventories, and
      the Reasons for Exercise Inventory of Silberstein, Striegel-Moore, Timko, and
      Rodin. Contrary to Cash, et al.'s findings, only health and fitness reasons were
      predictive of women's frequency of exercise, and women's dissatisfaction with
      specific bodily attributes was not significantly related to any reasons for
      exercising; however, like women in their sample, the current students who
      experienced more situational body dissatisfaction exercised for appearance and
      weight control. Sex comparisons indicated similar dissatisfaction with specific
      bodily attributes among men and women, but values were not significantly
      associated with any reasons for exercising. Women reported higher situational
      body dissatisfaction and exercising for appearance-related reasons more than men.
      Current participants may represent a more diverse group than previously tested,
      and the inventory's factor structure may not be generalizable to men and women.

PMID- 9638774
TI  - Stability and variability of dream content.
AB  - The present study investigated the stability and variability, respectively, of
      selected dream content measures derived from diary dreams. The within-subject
      correlations were small when dream length was controlled. To obtain sufficient
      reliability for all scales dream series of 20 dreams or more would be necessary.

PMID- 9638775
TI  - Clinical, bacteriological and epidemiological aspects of clinical mastitis in
      Israeli dairy herds.
AB  - A 4-year retrospective study was performed to determine the clinical,
      bacteriological and epidemiological aspects of acute clinical mastitis in seven
      Israeli dairy herds. A total of 1124 clinical mastitis cases were detected by
      abnormal changes in the milk and udder with concurrent decrease of at least 25%
      in daily milk production. A total of 1190 quarters were affected with clinical
      mastitis in 1089 cows. The rear quarters had a higher incidence risk (64.7% of
      quarter cases) than the front quarters. The annual herd-year-incidence varied
      from 4.2 to 126.8 cases/100 cows/year. The whole-lactation incidence risk (LIR)
      was 20.8 per 100 lactations. LIR increased from the first to fifth lactation and
      then decreased. Most clinical mastitis cases were associated with coliform
      bacteria (60.2% of cases), environmental streptococci (18.6%), coagulase-negative
      staphylococci (8.7%) and samples from which no bacterial growth was detected
      (8.1%). Most cases of clinical mastitis occurred in the early stages of
      lactation, with 51.4% of all cases, 52.3% of coliform cases and 54.6% of
      environmental streptococci mastitis cases occurring during the first 4 months of
      lactation. The median days in milk at diagnosis was 118 days. The incidence was
      lower in the dry summer months. The ratio of peak to low incidence was 1.62 with
      a calculated peak incidence in January.

PMID- 9638776
TI  - Multiple sources of Escherichia coli O157 in feedlots and dairy farms in the
      northwestern USA.
AB  - Samples from cattle, other domestic and wild animals, flies, feeds, and water
      troughs were collected from 12 cattle farms and tested for Escherichia coli O157.
      E. coli O157 was isolated from bovine fecal samples on all 12 farms with a within
      herd prevalence ranging from 1.1% to 6.1%. E. coli O157 was also found in 1 of 90
      (1.1%) equine fecal samples, 2 of 65 (3.1%) canine fecal samples, 1 of 200 pooled
      bird samples (0.5%), 2 of 60 pooled fly samples (3.3%), and 10 of 320 (3.1%)
      water-trough sample sets (biofilm and water). No E. coli O157 were isolated from
      300 rodents, 33 cats, 34 assorted wildlife, or 335 cattle feed samples.
      Indistinguishable pulsed-field gel electrophoresis patterns of XbaI digested
      chromosomal DNA and Shiga toxin types were observed for bovine and water-trough
      isolates from two farms and for one equine and two bovine isolates from one farm.

PMID- 9638777
TI  - Seroprevalences to Toxoplasma gondii in privately-owned dogs in Taiwan.
AB  - The prevalences of IgG and IgM antibodies to Toxoplasma gondii in pet dogs in
      Taiwan were measured by using both a kinetics-based enzyme-linked immunosorbent
      assay and immunoblotting. A logistic regression model with five factors (sex,
      age, weight, breed, domain) was analyzed. Pet dogs (n = 658) had seroprevalence
      of 7.9%, and had IgG and IgM geometric mean titers of 1:50 and 1:31,
      respectively. Older or heavier pet dogs had higher odds of seropositivity than
      younger or lighter dogs. Also, mixed-breed dogs had higher odds of seropositivity
      than pure-bred dogs.

PMID- 9638778
TI  - Biological predictors for early clinical mastitis occurrence in Holstein cows
      under field conditions in France.
AB  - Individual risk factors for clinical mastitis within the first month of lactation
      (early clinical mastitis, ECM) were analyzed in 695 Holstein multiparous cows
      (561 ECM- and 134 ECM+) which were clinical mastitis-free during the previous
      lactation. They belonged to 44 herds from the French Brittany region and were
      surveyed for 4 years. Individual biological parameter levels during the last 2
      months of gestation, production of the preceding lactation and calving conditions
      and health were the available explanatory variables. The construction and
      explanation model used multiple logistic regression run with herd as a fixed
      effect. High precalving plasma ceruloplasmin oxidase (p < 0.01) and low glutamate
      dehydrogenase (p < 0.05) activities, high 305-day previous-lactation milk yield
      (p < 0.001) and milk protein content at the last milk-test day before drying-off
      (p < 0.01) were the significant risk factors for ECM occurrence. Intensive
      production and unsatisfactory dietary conditions (energy and antioxidants) would
      increase ECM risk in the dairy cow. Further studies should be conducted to
      determine if metabolic and/or genetic factors could explain the relationship
      between ceruloplasmin and subsequent ECM occurrence.

PMID- 9638779
TI  - Associations between milk-protein production and reproduction, health, and
      culling.
AB  - Associations between protein production and individual-cow reproductive
      performance, health, and culling were investigated in a 2-year observational
      study involving a convenience sample of 75 Ontario, 5 Alberta, and 3 Nova Scotia
      dairy farms. Protein production was defined by 305-day lactation protein yields
      and by estimated breeding values for protein yield. After controlling for the
      level of milk production, herd, parity, breed, and season of calving, there were
      no significant associations between either measure of protein production and days
      open or days to first breeding. The only associations between protein production
      and disease were small positive associations between the estimated breeding value
      for protein yield and cystic ovaries and mean lactation somatic cell count. The
      risk of culling, after controlling for the level of milk production, was
      negatively associated with previous-lactation 305-day protein yield for parity
      three animals only. The estimated breeding value for protein yield had a small
      negative association with the overall risk of culling, although the associations
      were not significant for individual lactations.

PMID- 9638780
TI  - Measurement of digestive disorders in the piglet at weaning and related risk
      factors.
AB  - A cohort study was carried out in France about postweaning digestive disorders in
      the piglet. One hundred and six farrow-to-finish farms were involved. In each of
      them, a batch of contemporary piglets was considered. A total of 12,034 piglets
      were ear-notched, evaluated during the suckling phase and weighed at weaning, at
      14 and 28 days postweaning. Postweaning diarrhoea and mortality were recorded
      daily. Data were collected about diet composition and feed intake, housing and
      husbandry throughout the period. Weaning weight was 8.1 kg and weaning age was
      27.2 days on average. Diarrhoea occurred in the pens after a 3-4-day latency
      period. Prevalence was maximum around 7 to 9 days after weaning and remained high
      until 21 days after weaning. Mortality was moderate (1.9%). Average daily gains
      were 283 and 489 g for the two subsequent 14-day periods postweaning. Descriptive
      multivariate methods indicated a strong pattern between diarrhoea, mortality and
      growth. The main risk factors associated with the digestive disorders were
      determined. The hygiene level at the reception of the piglets (cleanliness, level
      of temperature), management and husbandry level (air quality, group size and
      stocking procedure) were found to be important factors leading to risky or secure
      profiles. In addition, the feed intake of the piglet during the first week
      postweaning was strongly associated with the severity of the digestive disorders
      over the whole 28-day postweaning period of observation. It is concluded that
      prevention of postweaning digestive disorders could be based on the control of
      zootechnical conditions.

PMID- 9638781
TI  - Gender differences in outcomes among patients with cancer.
AB  - This study examined gender differences in 162 female and 65 male patients with
      cancer referred to home care. Data were collected before hospital discharge using
      the Multidimensional Functional Assessment Questionnaire, the Karnofsky
      Performance Status, and the Quality of Life-Cancer Scale. Controlling for age and
      stage of disease, the results showed that men reported significantly more cancer
      related impairments, more limitations in activity of daily living, and poorer
      social resources than women. No gender differences were found in quality of life,
      perceived emotional health, perceived physical health, performance status, and
      comorbidity. Significant predictors of self-care activities were: for women
      perceived physical health, Karnofsky Performance Status, and stage of disease
      (58% variance explained); for men Karnofsky Performance Status and medication
      taken (67% variance explained). Gender differences should be considered in
      discharge planning to provide appropriate home care services for male and female
      patients with cancer.

PMID- 9638782
TI  - Reducing distress in cancer patients with an orientation program.
AB  - The purpose of this study was to test a brief orientation program for reducing
      anxiety, depressive symptoms, and overall distress in cancer patients at their
      initial clinic visit. One hundred and fifty consecutively referred patients seen
      in an oncology outpatient clinic were randomly assigned to an intervention or
      usual care control group. The intervention group received a clinic tour, general
      information about clinic operations, and a question and answer session with an
      oncology counselor. Outcome measures included the State-Trait Anxiety Inventory
      (STAI), the Brief Profile of Mood States (POMS), the Center for Epidemiologic
      Studies-Depression (CES-D) Scale, and an oncology clinic questionnaire which were
      administered at the initial clinic visit and follow-up. There were no
      statistically significant clinical or demographic differences between groups at
      initial assessment. At follow-up, the intervention group had lower state anxiety,
      lower overall distress, and fewer patients reporting depressive symptoms.
      Patients in the intervention group demonstrated significantly more knowledge
      about clinic operations and greater satisfaction with care. These data provide
      evidence that anxiety, distress and depressive symptoms can be reduced with an
      orientation program. This finding has particular relevance in the early stages of
      diagnosis where patients may suffer symptoms of anxiety and depression.

PMID- 9638783
TI  - A comparison of adjuvant psychological therapy and supportive counselling in
      patients with cancer.
AB  - This study compared the effectiveness of two psychological treatments in a group
      of 57 patients with various types of cancer attending the Royal Marsden Hospital.
      Patients referred for psychiatric assessment who met criteria for an abnormal
      adjustment reaction were randomly allocated to either 8 weeks of Adjuvant
      Psychological Therapy (APT), a problem-focused, cognitive behavioural treatment
      programme, or 8 weeks of a comparison treatment of supportive counselling. At 8
      weeks from the baseline assessment, APT had produced a significantly greater
      change than the counselling intervention on fighting spirit, helplessness, coping
      with cancer, anxiety, and self-defined problems. At 4 months from baseline, APT
      had produced a significantly greater change than counselling on fighting spirit,
      coping with cancer, anxiety and self defined problems. It is concluded that APT
      produces greater change in anxiety, adjustment to cancer and use of coping
      strategies than a non-directive, supportive intervention over an 8 week period of
      treatment. This difference persists at follow up 4 months after baseline
      assessment.

PMID- 9638784
TI  - Spanish version of the Rotterdam Symptom Check List: cross-cultural adaptation
      and preliminary validity in a sample of terminal cancer patients.
AB  - We report on the process of adaptation into Spanish of the Rotterdam Symptom
      Check List (RSCL). The original version was translated and back-translated by
      professional bilingual translators. A quantitative rating method was used to
      select the items to include in the final Spanish version. Validity (discriminant
      and construction) and reliability were test in 118 terminal cancer patients. In
      addition to the RSCL the Nottingham Health Profile (NHP) and the Karnofsky
      Performance Status (KPS) were used. The RSCL showed different ratings on all
      scales according to the functional level of the patients. The scales were
      moderately to highly correlated with the NHP (from 0.48 to 0.71). Internal
      consistency, measured by Cronbach's alpha coefficient ranged from 0.74 (physical)
      to 0.90 (activity). Twenty-four hours test-retest intraclass correlation
      coefficient ranged from 0.71 to 0.88. The results of this study suggest that the
      Spanish version of the RSCL is conceptually equivalent to the original. More
      research is needed to assess the responsiveness of the version before using it in
      clinical trials.

PMID- 9638785
TI  - Strategies of information disclosure to Chinese cancer patients in an Asian
      community.
AB  - There is little information available on strategies of information disclosure
      used by doctors in the care of patients with cancer. This report focuses on the
      style of disclosure used by doctors when giving diagnostic and prognostic
      information to patients with cancer. Among 46% of 133 surgeons and
      radiotherapists interviewed, disclosure of diagnosis involved a sudden approach
      (information given outright at one sitting). Less commonly used (19%) was a
      gradual disclosure style. Of the remainder who disclosed, more than half did so
      through the family or left it to the family to tell the patient. Doctors'
      specialty and patients' requests for prognostic information dictated disclosure
      style most frequently. Single people were more likely to have information
      disclosed to their families than were married people. While anecdotal accounts
      indicate negative reactions on the part of patients are a major reason for
      withholding such information, different disclosure style had little effect on
      doctors' reports of patient reactions to the bad news. Doctors perceived 25% of
      patients appeared to react 'with depression' but the remaining 75% appeared
      'calm'. These results suggest patients are more likely to be told bad news
      suddenly, and that doctors do not perceive that this impacts too negatively on
      patients. The high levels of reported preference for information about cancer in
      Hong Kong (Fielding and Hung, 1996) conflict with actual prevalence patterns. It
      seems that commonly cited anecdotal reasons for withholding information from
      cancer patients in Hong Kong are not sustained by the data produced in these
      studies.

PMID- 9638786
TI  - The quality and coping patterns of women's decision-making regarding breast
      cancer surgery.
AB  - This study addressed issues regarding the decision-making process used by women
      who had mastectomy as their surgical treatment for breast cancer. The seven
      criteria for quality decision-making and the conflict model proposed by Janis and
      Mann (1977) were used as the study's conceptual framework along with the notion
      by Simon (1957) of 'bounded rationality'. Four coping patterns emerged: vigilance
      (actively searches for information and advice), satisficing (being satisfied,
      chooses first solution that meets the desired objectives), complacency (accepts
      advice without questions or fully comprehending), and defensive avoidance
      (rationalises and avoids discussion and consideration of the problem). The
      participants primarily left the decision for surgical treatment of breast cancer
      to their surgeons using satisficing, complacency and defensive avoidance. When
      the option of lumpectomy was offered to some of the participants (34%), they
      rejected this treatment alternative using the coping patterns of satisfying and
      defensive avoidance. Those women who were not offered lumpectomy (66%) did not
      seek a rationale for not being given this alternative. The findings indicated
      that the women's decision-making process was halted in Stage 2 of the criteria
      for quality decision-making actively searched for and viewed a number of
      alternatives. The study's findings are discussed in relation to improving the
      quality of the decision-making process for women regarding their breast cancer
      surgical treatment.

PMID- 9638787
TI  - 'You don't want to lose your ovaries because you think 'I might become a man".
      Women's perceptions of prophylactic surgery as a cancer risk management option.
AB  - This preliminary study provides insight into the meaning of prophylactic surgery
      as a risk management strategy for women who have a familial risk of breast or
      ovarian cancer. Data were collected during observations of genetic consultations
      and in semi-structured interviews with 41 women following their attendance at
      genetic counselling. The option of prophylactic surgery was raised in 29
      consultations and discussed in 35 of the post-clinic interviews. Fifteen women
      said they would consider having an oophorectomy in the future and nine said they
      would consider having a mastectomy. The implications of undergoing oophorectomy
      and mastectomy were discussed during the post-clinic interviews. Prophylactic
      surgery was described by the counsellees as providing individuals with a means to
      (a) fulfil their obligations to other family members and (b) reduce risk and
      contain their fear of cancer. The costs of this form of risk management, were
      described as: (a) compromising social obligations; (b) upsetting the natural
      balance of the body; (c) not offering protection from cancer; (d) operative and
      post-operative complications; (e) the onset of menopause (f) the effects on body
      image, gender and personal identity and (g) potential effects on sexual
      relationships.

PMID- 9638788
TI  - Digestive and metabolic adaptations of ruminants to undernutrition, and
      consequences on reproduction.
AB  - In response to undernutrition, short- (days) and medium-term (weeks) adaptations
      are more pronounced for splanchnic organs than for other tissues. For the latter,
      the long-term response involves a sequential mobilization (fat > muscle > bone)
      with relative priorities differing among anatomical sites. Among chemical
      components, the body lipids are extensively used (up to 80%) in underfed animals,
      while the range of protein utilization is limited (up to 15-20%). The decrease in
      energy expenditure during undernutrition is mostly due to a short- and medium
      term decrease in feeding activity, and in the mass and activity of splanchnic
      tissues. In the long-term, energy expenditure and tissue masses decrease
      concomitantly, but there does not appear to be a significant decrease in
      expenditure per unit tissue weight. Nitrogen losses decrease in response to
      decline in nitrogen fluxes and also due to sparing by renal activities and
      sometimes by urea recycling. However, ruminants do not seem to be able to
      compensate for a low level of intake (below maintenance) by an increase in
      digestive efficiency. Numerous hormones (insulin, growth hormone, insulin-like
      growth factor I, catecholamines, thyroid hormones, cortisol, leptin, etc.) are
      involved in the changes during undernutrition of nutrient fluxes between tissues,
      either through control of synthesis and/or degradation in peripheral tissues
      (adipose tissue and muscle), or through hepatic conversions of substrates
      (gluconeogenesis, ureagenesis and ketogenesis), in order to maintain the
      constancy of the internal environment (homeostasis) and/or to sustain productive
      functions (teleophoresis). However, reproductive process may be blocked in
      underfed animals.

PMID- 9638789
TI  - Ubiquitin-proteasome-dependent proteolysis in skeletal muscle.
AB  - The ubiquitin-proteasome proteolytic pathway has recently been reported to be of
      major importance in the breakdown of skeletal muscle proteins. The first step in
      this pathway is the covalent attachment of polyubiquitin chains to the targeted
      protein. Polyubiquitylated proteins are then recognized and degraded by the 26S
      proteasome complex. In this review, we critically analyse recent findings in the
      regulation of this pathway, both in animal models of muscle wasting and in some
      human diseases. The identification of regulatory steps of ubiquitin conjugation
      to protein substrates and/or of the proteolytic activities of the proteasome
      should lead to new concepts that can be used to manipulate muscle protein mass.
      Such concepts are essential for the development of anti-cachectic therapies for
      many clinical situations.

PMID- 9638790
TI  - Effect of training on muscle strength and motor function in the elderly.
AB  - Overall muscle strength and mass decline 30-50% between the ages of 30 and 80.
      The loss of muscle mass, the so called sarcopenia, accounts for most of the
      observed loss of strength. A reduced specific muscle force has also been observed
      but its contribution to the decrease in strength with age remains unclear. The
      loss of muscle tissue is due to a decrease in the number of muscle fibres and
      atrophy of the type II muscle fibres. The declining strength reduces the capacity
      to carry out basic activities of daily life and puts people at risk for falls and
      dependence. Resistive strength training greatly increases muscle strength even in
      very old people. It produces muscle fibre hypertrophy and improves neural factors
      involved in force production. The recovered strength in turn enhances the
      physical performance and allows a more active and independent life towards the
      end of the life span.

PMID- 9638791
TI  - Alteration in nutritional status and diaphragm muscle function.
AB  - Diet-induced undernutrition causes deleterious changes in the structure and
      function of the diaphragm muscle. Diseases associated with somatic washing cause
      atrophy of the respiratory muscles. In cachectic subjects, the diaphragm muscle
      mass and thickness are reduced in proportion to the reduction in body weight. In
      addition, respiratory muscle strength and endurance are reduced more dramatically
      than the weight loss. This finding suggests that malnutrition induces a reduction
      in muscular mass which is associated with a decrease in contractility.
      Diaphragmatic weakness may increase the risk of respiratory failure in patients
      with chronic obstructive pulmonary disease (COPD). The primary goal of a
      successful nutritional programme is to improve the diaphragm strength by
      correcting the mineral, electrolyte and energetic disturbances at the muscular
      level, the latter being responsible for the decreased contractability associated
      with malnutrition.

PMID- 9638792
TI  - Duchenne muscular dystrophy: a model for studying the contribution of muscle to
      energy and protein metabolism.
AB  - Duchenne muscular dystrophy (DMD) is associated with a dramatic muscle mass loss.
      We hypothesized that DMD would be associated with significant changes in both
      energy and protein metabolism. We studied the resting energy expenditure (REE) in
      DMD and control children using indirect calorimetry, and their protein metabolism
      using an intravenous infusion of leucine and glutamine labeled with stable
      isotopes. In spite of a 75% muscle mass loss in the DMD children, the REE only
      decreased by 10%. DMD was associated with increased leucine oxidation but neither
      protein degradation nor protein synthesis were different from that of the
      controls. In contrast, whole body turnover of glutamine, an amino acid mainly
      synthesized in the muscle, was significantly decreased. These studies emphasized
      the quantitatively poor contribution of muscle to energy and protein metabolism
      in children. The qualitative impact of muscle mass loss on amino acid metabolism
      (glutamine) offers a fascinating field of research for the next few years and has
      therapeutic potential.

PMID- 9638793
TI  - IV perflubron emulsion versus autologous transfusion in severe normovolemic
      anemia: effects on left ventricular perfusion and function.
AB  - Intact cardiac compensatory mechanisms are necessary to maintain adequate tissue
      oxygenation during acute normovolemic hemodilution (ANH). Left ventricular (LV)
      perfusion, oxygenation and function were analyzed in an experimental whole-body
      model of profound ANH (Hct 9%) and effectiveness of a perfluorocarbon-based
      oxygen carrier in maintaining myocardial oxygenation and function was evaluated.
      A total of 22 anesthetized dogs were hemodiluted to Hct 20% followed by a
      simulated, controlled blood-loss phase in which dogs were randomized to either:
      (1) 1:1 exchange of lost blood with autologous red blood cells (RBC-group), (2)
      1:1 exchange with a colloid (control-group) and (3) 1:1 exchange with a colloid
      after a single dose of 1.8 g/kg BW perflubron i.v. (PFC-group). Myocardial oxygen
      delivery and consumption as well as endocardial perfusion were determined using
      radioactive microspheres. LV myocardial contractility (LV MC) was assessed from:
      (1) the relationship between maximum rate of LV pressure increase (LVdp/dtmax)
      and LV enddiastolic volume (LVEDV) and (2) analysis of the LV endsystolic
      pressure volume relationship (ESPVR). LV diastolic properties were reflected by
      (1) minimum rate of LV pressure increase (LVdp/dtmin), (2) slope and intercept of
      the enddiastolic pressure-volume relationship (EDPVR) and (3) the time-constant
      of isovolumic LV pressure decline "tau 1/2". Full sets of LV MC data were
      obtained from 18 dogs (n = 6 per group). LV MC (LVdp/dtmax-LVEDV relation)
      increased after perflubron administration. At the lowest Hct level, all
      parameters reflecting LV MC as well as LVdp/dtmin were significantly higher in
      the PFC-group than in the control-group. After profound normovolemic hemodilution
      (Hct 9%) superiority of LV MC and LV diastolic properties was found, when
      myocardial oxygenation was supported by i.v. perflubron emulsion, a temporary O2
      carrier.

PMID- 9638794
TI  - Type V phosphodiesterase inhibition modulates endogenous immunoreactivities of
      endothelin-1 and endothelial nitric oxide synthase in pulmonary arteries in rats
      with monocrotaline-induced pulmonary hypertension.
AB  - We evaluated the effects of oral administration of E4021 (100 mg/kg/day), a type
      V phosphodiesterase inhibitor, on immunoreactivities of endothelin-1, endothelin
      receptors, and nitric oxide synthases in pulmonary arteries in a rat model of
      pulmonary hypertension. Immunoreactivities of endothelin-1 and endothelial nitric
      oxide synthase were observed significantly less frequently, together with
      significant reduction of right ventricular overload and medial thickening in rats
      treated with E4021 than in the control with monocrotaline on day 28. The levels
      of plasma endothelin-1 and serum nitrite and nitrate were significantly lower in
      rats that received E4021 than in the control with monocrotaline. Oral
      administration of E4021 modulates endogenous immunoreactivities of endothelin-1
      and endothelial nitric oxide synthase with the improvement or right ventricular
      overload and medial thickening.

PMID- 9638795
TI  - Liver bilirubin UDP-glucuronosyltransferase activity in chronic nonhemolytic
      unconjugated hyperbilirubinemia of adults.
AB  - Ten adult patients with chronic nonhemolytic unconjugated (indirect)
      hyperbilirubinemia were analyzed by determining bilirubin uridine diphosphate
      glucuronosyltransferase activity according to a more physiological and sensitive
      method (9 control cases, 0.457 +/- 0.163 nmole/mg protein/min). There was no
      overlap of the enzyme activities of 2 cases with Crigler-Najjar syndrome (type
      II) (0.006 nmole/mg protein/min on average) and 6 cases with Gilbert's syndrome
      (0.051 +/- 0.016 nmole/mg protein/min). The enzyme activities in 2 patients with
      post-hepatitic hyperbilirubinemia were within the normal range. A new
      classification of nonhemolytic unconjugated hyperbilirubinemia in adults is
      proposed according to the results of this enzyme activity and the recent data on
      the gene mutation of this enzyme.

PMID- 9638796
TI  - The systemic vasodilatory action of protamine: is it inhibited or mediated by
      heparin?
AB  - The administration of protamine to neutralize the circulating heparin is common
      practice in cardiovascular surgery. The use of this drug is sometimes associated
      with hemodynamic alterations of varying degree and intensity (systemic
      hypotension, pulmonary hypertension and even cardiogenic shock). An intrinsic
      action of protamine has been suggested to be the cause of these vascular
      reactions. This action is blocked when protamine forms a complex with heparin,
      although in other cases it appears that the heparin-protamine complex is the
      factor responsible for these hemodynamic alterations. The aim of this
      experimental study was to characterize the vasodilatory action of protamine on
      the systemic circulation, determining whether or not it is dose-dependent; to
      analyze the role of endothelium; and to evaluate whether this vasodilatory effect
      is modified by the presence of heparin. MATERIALS AND METHODS: The abdominal
      aorta was dissected from eight New Zealand rabbits and then sectioned into
      vascular rings for study in an organ chamber. Mechanical disruption of
      endothelium was performed on some rings (n = 14). Once submaximal contraction was
      reached (ClK 80 mM), protamine sulfate with a final concentration in the organ
      chamber of 80-400 micrograms/ml was added to one of the groups (n = 12). In the
      second group (n = 12), equal concentrations of protamine were tested in the
      presence of heparin at a final concentration of 100 U/ml. RESULTS: The mean
      vasodilatation reached in the group of rings exposed only to protamine was 95.4
      +/- 1.5% with respect to the submaximal contraction induced with ClK. In the
      second study group, the rings were exposed to protamine at equally increasing
      concentrations (80-400 micrograms/ml) but with the presence of heparin in the
      organ chamber. The mean vasodilatation in this group was 90 +/- 1.5. No
      statistically significant differences in vasodilatation were found between this
      group and the protamine without heparin group. On the other hand, in the
      endothelium-denuded rings (n = 14) exposed to isolated protamine and to protamine
      heparin, no vasodilatory response was observed. CONCLUSION: Our results show that
      the administration in vitro of protamine induces endothelium-dependent
      vasodilatation of the systemic circulation. Likewise, this relaxing effect
      mediated through endothelium is not blocked when protamine forms a complex with
      heparin in comparable concentrations of both drugs. Based on these preliminary
      findings, we believe that in high-risk patients the prevention of systemic
      vasodilatation and cardiovascular collapse produced by protamine should move
      towards the use of other substances that can neutralize the anticoagulant effect
      of heparin or towards pre-medication guidelines that prevent these secondary
      effects in the case of protamine administration.

PMID- 9638797
TI  - Prevention of intestinal adhesions after laparotomy in a rat model--a randomized
      prospective study.
AB  - We prospectively studied the effect of a foam composite containing glycerin,
      propylene glycol, polyol, stearine, stearate and silicone oil, which is known to
      form a temporary barrier layer when applied to epithelial surface, on adhesion
      prevention in rats. The small intestine abrasion model was used for creation of
      adhesions. Sixty male Sabra rats of a mean weight of 295 +/- 23 g were randomly
      assigned into four groups: group 1 (n = 20) underwent laparotomy and abrasion;
      group 2 (n = 20) underwent laparotomy, abrasion and intraperitoneal instillation
      of the foam composite; group 3 (n = 10) underwent laparotomy with abrasion and a
      second laparotomy with adhesiolysis 2 weeks later; and group 4 (n = 10), was
      treated in the same way as group 3 but during the second laparotomy the foam
      composite was instilled intraperitoneally. All animals were relaparotomized 2
      weeks (groups 1 and 2) and 4 weeks (groups 3 and 4) after the initial laparotomy
      for adhesion scoring performed by a blinded independent investigator using the
      standard 0-3 adhesion grading score. Representative specimens of small intestine
      and liver from animals in groups 2 and 4 were analyzed. A significantly lower
      mean adhesion score was noted in group 2 (1.15 +/- 0.3) compared with that of
      group 1 (2.65 +/- 0.1) or group 3 (2.60 +/- 0.1) (P < 0.01). Group 4 had a
      significantly lower score (1.4 +/- 0.3) than group 3 or group 1 (P < 0.05). There
      was no significant difference in the mean adhesion score between groups 1 and 3.
      Histological examination revealed no evidence of residual foam composite or
      adverse reaction to its use in the intestine and liver. The foam composite tested
      may reduce the severity of intestinal adhesions after laparotomy and may also
      reduce the severity of recurrent adhesions after adhesiolysis. Intraperitoneal
      use of this composite is safe in rats. The exact mechanism of action is unclear
      but may be related to the formation of a temporary microlayer that coats the
      injured surface of the intestine and facilitates healing without adhesion
      formation. Further investigation is needed to evaluate its full potential.

PMID- 9638798
TI  - Resolving the genetics of resistance to infectious diseases.
AB  - The genetics of resistance to disease is an area of great interest in
      agriculturally important plant and animal species. Selective breeding for
      resistance to pathogens in plants, animals and insects has demonstrated that
      resistance and susceptibility to pathogens are controlled by both genetic and
      environmental factors. The immune loci causally involved in susceptibility and
      resistance to disease are currently unknown. However, novel enabling molecular
      technologies promise to assist in unravelling the genetics of the host response
      to infectious diseases in new ways, and ultimately to improve seed stock
      genetics.

PMID- 9638799
TI  - Constitutional and non-specific immunity to infection.
AB  - Most immunologists focus on elaborate non-specific and antigen-specific factors
      of reactive immunity produced by the vertebrate lymphoid system. Modern
      principles of immunogenic prophylaxis and therapy are based solely on the use of
      these agents. There is, however, a more effective system of specific resistance
      which is shared by all forms of life: hereditary constitutional immunity to
      infection and invasion. An explosive growth in knowledge of the constitutional
      immunogenic system has occurred during the past two decades. The author
      illustrates the nature and importance of constitutional immunity, using examples
      from genetics and molecular biology. Special attention is given to testing for
      genetic susceptibility to infection and genetic engineering of resistance.

PMID- 9638800
TI  - Immunoglobulin diversity, B-cell and antibody repertoire development in large
      farm animals.
AB  - The B-cell lineage, the antibodies produced by these cells and the
      diversification of the antibody repertoire are essential for the health and
      survival of all mammals. Cattle, sheep, swine and horses, unlike rodents and
      primates, develop their antibody repertoire from a relatively small number of VH
      (variable heavy) genes of one or several families and cattle, sheep and horses
      use almost exclusively lambda-light chains. These large farm animals appear to
      use templated mutation (gene conversion) in addition to untemplated (point)
      mutation in repertoire development; this may occur predominantly in the ileal
      Peyer's patches. Whether B-cell lymphogenesis is continuous throughout life--as
      in rodents and primates--or whether B cells are largely of the B-1 lineage and
      develop only in foetal and neonatal life, is uncertain. The fact that
      immunoglobulin D (IgD) is totally absent from swine and ruminants may be
      significant, as IgD is expressed weakly on rodent B-1 cells. Information on IgG
      subclass diversity in large farm animals is incomplete, except for sheep and
      cattle, and no information is available for any large farm animal to show whether
      T helper 1 (Th1) and Th2 responses correlate with the expression of any subclass
      antibody response, as is the case in rodents. All large farm animals exclusively
      use the mammary gland to transfer immunity to offspring, although the receptor
      involved in the transport of IgG into colostrum and milk has not been
      characterised. Efforts to standardise the nomenclature and measurements of
      antibodies and immunoglobulins in large farm animals are discussed, and a
      proposal currently under review concerning the standardisation of the
      nomenclature for bovine immunoglobulins is presented as a model.

PMID- 9638801
TI  - Antigen-specific immune response of porcine T lymphocytes to various pathogens.
AB  - The importance of swine in agriculture has resulted in a substantial increase in
      research efforts on the swine immune system during the past few years. A better
      knowledge of the porcine immune system is required before improved vaccination
      strategies, the design of more efficient vaccines and breeding for disease
      resistance will be able to contribute to a reduction in the extensive economic
      losses caused by the disabling effects of viral, bacterial and parasitic
      infections. T lymphocytes play a central role in the antigen-specific immune
      response to the various pathogens. To detect and characterise porcine T
      lymphocytes, monoclonal antibodies (mAbs) were raised against different leucocyte
      differentiation antigens and classified for specificity in two international
      workshops. These mAbs have enabled detailed studies to be made on specific cell
      populations involved in the porcine immune response to pathogens, on T
      lymphocytes and on the peculiarities of porcine T lymphocyte sub-populations:
      extra-thymic CD4+CD8+ T lymphocytes and a substantial proportion of CD2-TCR gamma
      delta+ T cells. Furthermore, these reagents and the increased knowledge of the
      immune system have allowed studies of the interactions of T lymphocyte sub
      populations with regard to different pathogens and the role which these play in
      infections.

PMID- 9638802
TI  - Cytokines orchestrating the immune response.
AB  - The author summarises the current knowledge of the major immune cytokines, their
      receptors and functions, and illustrates the pivotal role of cytokines in
      regulating immune responses. As researchers explore the factors which influence
      the genetics of disease resistance in livestock and poultry, alleles associated
      with differences in the expression of, and responsiveness to, cytokines will
      inevitably be defined. Variations in cytokine receptors, as well as in
      sensitivity to the rapidly expanding array of cytokine agonists and antagonists,
      will also be identified. These differences influence not only disease resistance
      but also potential disease pathology and speed of recovery from infection. The
      author concludes with a discussion of some uses of cytokines in clinical
      practice. This area is the subject of active exploration with clinical trials in
      many species, addressing issues such as immune system stimulation and disease
      treatment with cytokine proteins. As veterinarians use such new biotherapeutics,
      the issue of genetic control of responses to deliberate cytokine stimulation will
      become important to producers.

PMID- 9638803
TI  - Porcine major histocompatibility complex.
AB  - The major histocompatibility complex in swine (swine leucocyte antigen: SLA) is
      located on chromosome 7 with the class I and class III regions separated by the
      centromere from the class II region. The overall molecular organisation of the
      class I and III regions is well known, but further research is needed to
      establish that of the class II region. Approximately sixty genes have been
      characterised to date, including ten tightly packed SLA class I sequences. The
      exact number of functional polymorphic class I genes, as defined by serology,
      probably varies from one to four, depending on the haplotype. At least two other
      distantly class I-related gene families exist. The numerous and significant
      associations reported between SLA haplotypes and physiological traits are
      described. These traits include immune responsiveness to a variety of microbes
      and metazoan parasites, and male and female production and reproduction
      performance. The results obtained suggest that selection for specific SLA
      haplotypes may assist in the improvement of porcine production.

PMID- 9638804
TI  - The major histocompatibility complex of ruminants.
AB  - Studies of the major histocompatibility complex (MHC) of cattle over the past
      twenty years have revealed a reasonably detailed picture of the genetic
      organisation and function of the genes within this genetic system. Serological
      and biochemical analysis of lymphocyte cell surface antigens provided the first
      evidence for highly polymorphic MHC genes in cattle and other ruminant species.
      The MHC of cattle was thus named the bovine leucocyte antigen (BoLA) system.
      During the past 10 years, tools of molecular biology have been used to
      characterise the number of MHC genes, their sequence and fine structure in a
      number of ruminant species. Although individual MHC genes were found to have
      clear orthologues among ruminants and other mammalian species, the MHC of cattle,
      and probably that of sheep and goats, has a unique genetic organisation. Cattle
      have a class II gene cluster (class IIb region) which is physically distant from
      all the other MHC genes on the same chromosome. Moreover, genes involved in
      antigen processing, such as the proteosome subunit locus LMP2, are also found in
      the class IIb region, demonstrating that these genes need not be in close
      proximity to other MHC genes to function normally. The MHC class I and class II
      gene products of ruminants present processed peptides to T lymphocytes which
      mediate helper and cytotoxic functions. Identification of peptide binding motifs
      of cattle MHC class I molecules indicates that ruminant MHC molecules function in
      a similar manner to those of mice and humans. These functional studies provide a
      firm molecular basis for a number of well-documented associations with infectious
      diseases, although a detailed understanding of the immunogenetic mechanisms
      underlying these associations has yet to be elucidated.

PMID- 9638805
TI  - The major histocompatibility complex in fish.
AB  - The first major histocompatibility complex (MHC) molecule in fish was identified
      in 1990 using a polymerase chain reaction strategy with degenerate primers
      (thereby avoiding the problem of low sequence similarity between higher
      vertebrates and fish). Since that time, MHC in fish has attracted much attention,
      partly due to evolutionary aspects and partly because of the potential practical
      consequences for future fish breeding. Knowledge of the MHC molecules in fish has
      thus been growing extremely rapidly. All current data point to a functional MHC
      system in fish. There seem to be many loci and many alleles for both classes of
      MHC molecules, but a lack of knowledge about functional loci versus pseudogenes
      and non-classical loci is making it difficult at present to establish the exact
      number found within each species. Fish create a few surprises, such as the lack
      of a link between class I and class II regions in at least two teleost species.
      Data on other molecules which are physically or functionally linked to the MHC
      genes are currently emerging. To date, no studies have established the functional
      implications of the MHC molecules in fish but, considering the molecular data
      available, such an achievement will undoubtedly occur soon. Fish may well offer a
      unique opportunity for identifying correlations of MHC with resistance or
      susceptibility to diseases.

PMID- 9638806
TI  - The chicken major histocompatibility complex and disease.
AB  - The chicken major histocompatibility complex (MHC), or B complex, consists of
      several clusters of highly polymorphic genes, some of which are associated with
      disease resistance. The class I and class II antigens resemble their mammalian
      counterparts in the encoded protein structure. The class IV region encodes the B
      blood group antigens, which are readily identified by serological blood-typing.
      The class III region appears to be divided in chickens, with some elements that
      are MHC-linked and others that map elsewhere. In addition the Rfp-Y system, which
      bears a strong similarity to the MHC, maps to the opposite side of the nucleolar
      organiser region on the same microchromosome as the MHC. Each class of MHC genes
      is a potential candidate for a role in disease resistance. The MHC genes show
      associations with response to diseases as diverse as virally induced neoplasia,
      bacterial, parasitic and auto-immune diseases.

PMID- 9638807
TI  - Genetic resistance to parasitic infection.
AB  - The ability of animals to resist infections with parasites is genetically
      determined and therefore variable between individuals or breeds of a given host
      species. Such variation may involve innate (non-immunological) and acquired
      (immunologically mediated) resistance mechanisms, and is determined by both major
      histocompatibility complex (MHC)-linked and non-MHC genes. Resistance is
      inherited as a dominant trait, with heritability often exceeding 0.3. Genetic
      variation can be exploited to improve the capacity of domestic animals to resist
      parasitic infection. Methods to achieve this exploitation are discussed in
      relation to gastrointestinal nematode infections in sheep.

PMID- 9638808
TI  - Trypanotolerance, an option for sustainable livestock production in areas at risk
      from trypanosomosis.
AB  - Trypanosomosis is one of the major constraints on animal production in areas of
      Africa which have the greatest potential for significant increases in domestic
      livestock populations and livestock productivity. While the eradication of
      trypanosomosis from the entire continent is an unrealistic goal, considerable
      effort has been invested in the control of this disease through the use of
      trypanocidal drugs, management of the vector and exploitation of the genetic
      resistance exhibited by indigenous breeds. There is little hope that a
      conventional, anti-infection vaccine will be produced in the near future. Drug
      resistance is developing faster than generally thought. The control of the tsetse
      fly has been attempted over many decades. The decreasing efficacy of available
      trypanocidal drugs and the difficulties of sustaining tsetse control increase the
      imperative need to enhance trypanotolerance through selective breeding, either
      within breeds or through cross-breeding. Trypanotolerance has been defined as the
      relative capacity of an animal to control the development of the parasites and to
      limit their pathological effects, the most prominent of which is anaemia. A major
      constraint on selection for trypanotolerance in cattle, for both within-breed and
      cross-breeding programmes, has been the absence of practical reliable markers of
      resistance or susceptibility. Distinct humoral immune response to trypanosome
      infection is the major feature of bovine trypanotolerance. The role that these
      responses play in the control of infection or disease is being addressed by
      ongoing research, but remains a matter of speculation at present. Results in
      recent years have shown that packed cell volume (PCV) in particular and
      parasitaemia, the two principal indicators of trypanotolerance, are strongly
      correlated to animal performance. However, although direct effects of trypanosome
      infections on PCV and growth are obvious, more sensitive diagnostic methods for
      reflecting parasite control are required so that individual animals can be
      categorised reliably for their parasite control capability. One key finding is
      the major contribution made by each of the indicators evaluated to the overall
      trypanotolerance variance. Preliminary genetic parameters for PCV provide
      evidence that trypanotolerance is not only a breed characteristic but is also a
      heritable trait within the N'Dama population; this brings new opportunities for
      improved productivity through selection for trypanotolerance. More reliable
      estimation of genetic parameters of the indicators may well show that these
      parameters must be handled simultaneously for optimal progress. This would
      require diagnostics for assessing parasite control capability that identify
      trypanosome species more accurately, especially in mixed infections. A major
      advantage of trypanotolerant livestock, particularly N'Dama cattle, is the
      resistance or adaptation of this breed to many of the important pathogenes which
      prevail in the sub-humid and humid tropics. Research on practical indicators of
      resistance to these conditions will be required to establish relevant integrated
      strategies based on disease-resistant livestock. Selective breeding will require
      the integration of the traits that farmers hold important for their production
      systems.

PMID- 9638809
TI  - Murine leishmaniosis: a paradigm for the importance of T helper 1 and T helper 2
      cells.
AB  - The murine model of leishmaniosis is a prototypic example for the critical role
      played by T helper cells in immunity to pathogens. Cytokines, such as interleukin
      12 and interleukin-4, are the major regulatory factors for differentiation of
      naive T helper cells into T helper 1 and T helper 2 cells, respectively. T helper
      1 cells, which are cellular immune mechanisms involving gamma interferon
      production, are associated with protection against murine leishmaniosis. Loss of
      T helper 1 activity (i.e., reduced gamma interferon production and lack of
      macrophage activation) leads to a fatal progressive course of murine
      leishmaniosis. Knowledge of the murine model of leishmaniosis is now contributing
      to studies of infectious diseases in humans, livestock and companion animals.
      Greater insight into the pathogenesis, diagnosis and therapy of infectious
      diseases will be gained from the analysis of cytokine-dependent regulation of T
      helper responses during infection. In particular, the development of prophylactic
      and therapeutic vaccines will benefit significantly from these studies.

PMID- 9638810
TI  - The use of vaccines and genetically resistant animals in tick control.
AB  - The control of ticks and diseases transmitted by ticks is extremely difficult.
      Application of acaricides is the most common prophylactic and therapeutic control
      measure against these ectoparasites. The selection of tick strains which are
      resistant to these products, the appearance of chemical residues in milk and
      meat, and environmental pollution resulting from the use of acaricides pose real
      problems. This article deals with aspects of current work on the alternative
      control of ticks and places special emphasis on the development of vaccines and
      the utilisation of genetically resistant animals.

PMID- 9638811
TI  - Genetic resistance to bacterial diseases of animals.
AB  - Despite traditional disease control measures, losses attributable to infectious
      diseases continue to impede the livestock industries. An alternative approach to
      this problem is genetic disease resistance involving both immune and non-immune
      mechanisms, which is the inherent capacity of a previously unexposed animal to
      resist disease when challenged by pathogens. Although the nurturing environment
      influences variability in disease expression, natural resistance has been found
      to be inheritable and is transmitted from parent to offspring. Thus, an
      alternative approach to enhancing animal health management systems is to increase
      the overall level of genetic resistance at herd and population levels by using
      selective breeding programmes. The purpose of this review is to bring
      veterinarians, regulatory officials, industry representatives and animal
      technicians up to date with the principles and applications of genetic resistance
      as an adjunct to traditional interventions to control bacterial diseases of
      livestock. Although genetic resistance to bacterial diseases is often regulated
      by multiple genes controlling different processes of the host-pathogen
      interaction, the genetics of natural resistance is being unravelled increasingly
      by identification and characterisation of candidate genes, microsatellite markers
      and comparative gene mapping, to develop more practical methods of application.

PMID- 9638812
TI  - Mx proteins: mediators of innate resistance to RNA viruses.
AB  - Mx proteins are interferon-induced members of the dynamin superfamily of large
      guanosine triphosphatases. These proteins have attracted attention because some
      display antiviral activity against pathogenic RNA viruses, for example against
      members of the orthomyxovirus (influenzavirus) family or the bunyavirus family.
      Transfected cells and transgenic mice expressing Mx proteins are highly resistant
      to Mx-sensitive viruses, demonstrating that Mx proteins are powerful antiviral
      agents. In humans, synthesis of MxA is observed during self-limiting viral
      infections and may thus promote recovery from disease.

PMID- 9638813
TI  - Genetic control of host resistance to flavivirus infection in animals.
AB  - Flaviviruses are small, enveloped RNA viruses which are generally transmitted by
      arthropods to animals and man. Although flaviviruses cause important diseases in
      domestic animals and man, flaviviral infection of animals which constitute the
      normal vertebrate reservoir may be mild or sub-clinical, which suggests that some
      adaptation between virus and host may have occurred. While this possibility is
      difficult to study in wild animals, extensive studies using laboratory mice have
      demonstrated the existence of innate, flavivirus-specific resistance. Resistance
      is heritable and is attributable to the gene Flvr, which is located on chromosome
      5 in this species. The mechanism of resistance is at present unknown, but acts
      early and limits the replication of flaviviruses in cells. While some evidence
      supports a role for Flvr in enhancing the production of defective interfering
      virus, thereby restricting the production of infectious virus, other reports
      suggest that Flvr interferes with either virus RNA replication or RNA packaging.
      Recent research suggests that cytoplasmic proteins bind to the viral replication
      complex and that allelic forms of these proteins in resistant mice may restrict
      the production of infectious progeny. Apparent resistance to flaviviruses has
      been described in other vertebrates, although it remains to be seen if this is
      attributable to a homologue of Flvr. Nonetheless, knowledge gained of the
      characteristics and function of Flvr in mice should be applicable to other host
      species, and improvement of resistance to flaviviral infection in domestic
      animals by selective breeding or gene technology may ultimately be possible.

PMID- 9638814
TI  - Genetic resistance to avian viruses.
AB  - Viral infections of poultry can be catastrophic in terms of both welfare and
      economics, and although vaccines have been very successful in combating these
      diseases, new forms of viruses have evolved which present increasing difficulties
      for vaccine control. Differences in genetic susceptibility are known to exist for
      many of the major viral pathogens of poultry. Consequently, an increase in the
      level of genetic resistance provides a possible means of enhancing protection of
      flocks. This is particularly feasible where specific resistance genes have been
      identified, as in the case of avian leukosis and Marek's disease, and the
      development of genetic maps of the chicken has offered new possibilities for the
      identification of further resistance genes. It has also become clear that there
      are genetic differences in the response to live attenuated vaccine viruses, and
      new possibilities exist to manipulate the genetics of host flocks so that the
      effect of vaccination can be optimised.

PMID- 9638815
TI  - Myxoma virus in rabbits.
AB  - Myxoma virus in European rabbits (Oryctolagus cuniculus) is one of the best
      documented examples of host-virus co-evolution. In the natural hosts (Sylvilagus
      brasiliensis or S. bachmani rabbits in the Americas), myxoma virus causes a
      benign cutaneous fibroma. In European rabbits, however, myxoma virus causes the
      fulminant disease, myxomatosis. When introduced into wild European rabbit
      populations in Australia, Europe and Great Britain, the virus was initially
      highly lethal, killing in excess of 99% of infected rabbits. Development of
      resistance was encouraged by the emergence of attenuated virus strains which
      allowed the survival of moderately resistant rabbits. This may have occurred more
      rapidly in hot climates, as high ambient temperatures increase the survival rate
      of infected rabbits. Resistant rabbits are less effective transmitters of the
      virus and this may encourage the emergence of more virulent virus strains. Little
      is known of the mechanism of resistance. There have been suggestions of non
      genetic resistance. However, these are yet to be confirmed experimentally.

PMID- 9638816
TI  - Fv1, the mouse retrovirus resistance gene.
AB  - A number of genes which affect the susceptibility of mice to infection by
      retroviruses have been described. One of the most interesting of these genes is
      Fv1 (Friend virus susceptibility 1), which acts at a stage in the retroviral life
      cycle following virus entry into the cell but prior to integration and formation
      of proviral structures. A detailed understanding of the mode of action of Fv1
      might be expected to shed fresh light on early steps of the retroviral
      replication, although progress has been slow in this area due to uncertainty
      about the nature of the Fv1 gene. The recent cloning of Fv1 by a positional
      approach fills this gap in current knowledge. Fv1 appears to be derived from a
      fragment of a retroviral genome, an observation that may suggest novel approaches
      to the control of retroviral replication.

PMID- 9638817
TI  - The use of transgenic mice in the investigation of transmissible spongiform
      encephalopathies.
AB  - The prion, the transmissible agent that causes spongiform encephalopathies such
      as scrapie, bovine spongiform encephalopathy and Creutzfeldt-Jakob disease, is
      believed to be devoid of nucleic acid and to be identical to PrPSc (prion
      protein: scrapie form), a modified form of the normal host protein PrPC (prion
      protein: cellular form) which is encoded by the single copy gene Prnp. The
      'protein only' hypothesis proposes that PrPSc, when introduced into a normal
      host, causes the conversion of PrPC into PrPSc; it therefore predicts that an
      animal devoid of PrPC should be resistant to prion diseases. The authors
      generated homozygous Prnp(o/o) ('PrP knockout') mice and showed that, after
      inoculation with prions, these mice remained free from scrapie for at least two
      years while wild-type controls all died within six months. There was no
      propagation of prions in the Prnp(o/o) animals. Surprisingly, heterozygous
      Prnp(o/+) mice, which express PrPC at about half the normal level, also showed
      enhanced resistance to scrapie despite high levels of infectious agent and PrPSc
      in the brain at an early stage. After introduction of murine PrP transgenes,
      Prnp(o/o) mice became highly susceptible to mouse--but not to hamster--prions,
      while the insertion of Syrian hamster PrP transgenes rendered the mice
      susceptible to hamster prions but much less susceptible to mouse prions. These
      complementation experiments enabled the application of reverse genetics. The
      authors prepared animals transgenic for genes encoding PrP with amino terminal
      deletions of various lengths and found that PrP that lacks 48 amino proximal
      amino acids (which comprise four of the five octa repeats of PrP) is still
      biologically active.

PMID- 9638818
TI  - Conventional breeding programmes and genetic resistance to animal diseases.
AB  - The power of selection is illustrated by the increase in the average annual yield
      of dairy cows in Sweden in kg fat-corrected milk from 2,500 kg in the year 1900
      to 8,200 kg in 1997. More than a half of this improvement has a genetic origin.
      The breeding goal for dairy cattle has successively been broadened to cover
      traits other than production. The prerequisites for a successful breeding
      programme and the consequences of the process are presented in this article. The
      dramatic improvement of the reproduction techniques and statistical tools for
      genetic evaluation of breeding stock and selection, which have occurred during
      the last 50 years, is also discussed. The factors which affect the genetic gain
      are described in detail to demonstrate the possibility of making genetic gains in
      traits reflecting disease resistance. The Swedish procedure of disease recording
      and the procedures for genetic evaluation of fitness traits, such as disease
      resistance and female fertility, are described. The existence and consequences of
      negative genetic correlations between production and fitness traits are dealt
      with, as is the procedure for multi-trait selection. An illustration of methods
      for performing multi-trait selection in real life, and the consequences of such
      selection in an envisaged Nordic selection scheme, are given. Finally, the
      authors review the present genetic trends for fitness traits of dairy cows in
      Sweden.

PMID- 9638819
TI  - Biological principles of heredity of and resistance to disease.
AB  - Understanding the biological principles of disease heredity and resistance to
      disease is a prerequisite for the incorporation of these factors into multi-trait
      breeding programmes. Mutations represent an evolutionary aspect of disease. The
      author reviews patterns of Mendelian inheritance and possible causes of non
      Mendelian inheritance, such as multifactorial inheritance, expansion of
      trinucleotide repeats, mitochondiral inheritance and genomic imprinting, in
      relation to diseases of domestic animals. Host-pathogen interactions underlie
      genetic variability in resistance to disease. Infectious pathogens endowed with a
      high potential for evolutionary change use this potential to evade various host
      defence mechanisms. This interaction may have a competitive or co-evolutionary
      character. The host immune system copes with the variability of pathogens by
      using the potential of genetic diversity of lymphocytes in immunoglobulin, T-cell
      receptor and major histocompatibility complex genes. Possible mechanisms for
      maintenance of this diversity are discussed in the context of selection for
      disease resistance.

PMID- 9638820
TI  - Breeding for disease resistance in Merino sheep in Australia.
AB  - Breeding for disease resistance in Merino sheep in Australia has attracted
      considerable research and development attention. Increased labour costs, the
      reduced efficacy of common anthelmintics and insecticides, consumer demand for
      products which are free of chemicals and the poor prognosis of alternative long
      term control strategies are all forcing sheep breeders to contemplate the best
      animal health options available, including selective breeding for resistance. The
      three major diseases which affect sheep production include gastrointestinal
      nematode parasites, flystrike (cutaneous myiasis) and footrot. Genetic
      improvement has been shown to be feasible in all these diseases, possibly with
      little adverse effect on genetic progress in other production traits. Programmes
      for resistance to internal parasites to be included in practical breeding
      programmes are now in progress. This paper deals with the incentives for focusing
      on the three major diseases in Merino sheep, the potential sources of genetic
      variation, and the means to exploit these sources of variation. The authors also
      highlight gains and benefits achieved in experimental selection flocks, and the
      difficulties and options available for commercial breeders.

PMID- 9638821
TI  - Genomic approaches to the improvement of disease resistance in farm animals.
AB  - As a result of the difficulties in improving disease resistance in farm animals
      by traditional phenotype selection, the achievement of such improvement is one of
      the most important applications of genome research. The major hurdle to this
      important goal is the collection of informative disease records to enable the
      segregation of disease resistance loci (DRL) to be traced in pedigrees. This
      paper reviews the principles for DRL identification by association analyses or by
      linkage analyses. Once linkage has been established, the location of the DRL may
      be further refined, a process which may eventually lead to the molecular
      characterisation of the causative gene(s) and mutation(s). A reliable map
      assignment of a DRL is sufficient for the practical utilisation of this
      knowledge, since the inheritance of the DRL can be traced by flanking markers.
      Marker-assisted selection concerns the use of linked markers for selection within
      populations, while marker-assisted introgression is used if DRL alleles are
      introgressed from a donor (resource) population.

PMID- 9638822
TI  - Genetic databases: online catalogues of inherited disorders.
AB  - Current information on inherited disorders in domestic animals is available on
      the internet: Online Mendelian inheritance in animals (OMIA) and Mendelian
      inheritance in sheep (MIS) are the two major sources of information. OMIA was
      created (and is maintained) by workers at the University of Sydney. MIS has been
      compiled by the Committee on Genetic Nomenclature of Sheep and Goats (COGNOSAG),
      an international group of geneticists. In the future, similar catalogues for
      other species (starting with goats and cattle) will be made available by
      COGNOSAG. Electronic access to this information is freely accessible on the world
      wide web at http:/(/)www.angis.su.oz.au/Databases/BIRX/om ia (for OMIA),
      http:/(/)probe.nalusda.gov:8300/animal/omia.h tml (for OMIA in the United States
      of America) and at http:/(/)www.angis.org.au/Databases/BIRX/mis (for MIS).

PMID- 9638823
TI  - Lessons from gene knockouts.
AB  - The authors describe the technique for the application of homologous
      recombination in embryonic stem cells, which is now widely used to engineer mice
      which carry specific knockouts of genes. A summary is given of some of the
      knowledge of the pathogenesis of and resistance to infections with parasites,
      bacteria, or viruses which has accumulated during recent years, based on the
      investigation of knockout mice. Special emphasis is placed on knockout animals
      which lack components of the cytokine network, lack genes which are critical for
      the correct presentation of antigens or are deficient in different immune cell
      subsets. In addition, a brief explanation is offered of the possibilities for
      inducing targeted deletions or mutations in genes of livestock species (e.g., by
      nuclear transfer or by mutagenesis using the alkylating agent N-ethyl-N
      nitrosourea) which could lead to the breeding of animals which are resistant to
      infectious diseases in the future.

PMID- 9638824
TI  - Transgenic approaches to the increase of disease resistance in farm animals.
AB  - Molecular genetics and reproductive biology techniques enable the transfer of
      foreign DNA into mammals. Novel approaches to modify disease resistance or
      susceptibility in livestock are justified by economic and animal welfare
      concerns. Current research on the improvement of disease resistance by gene
      transfer focuses on three main strategies, as follows: a) somatic gene transfer,
      i.e., nucleic acid vaccines b) deletive germ-line gene transfer, i.e., gene
      knockout c) additive germ-line gene transfer. These strategies aim at either the
      transient or stable expression of components known to influence non-specific or
      specific host defence mechanisms, or the disruption of genes known to cause
      susceptibility to disease. Referring to the source of the effective agent and the
      site and mode of action, the strategies are termed 'genetic', 'congenital',
      'intracellular' and 'extracellular' immunisation. Each gene transfer experiment
      has to be evaluated carefully with respect to the potential to create novel cases
      of pathogen resistance or to lose species barriers or cell-type restrictions.

PMID- 9638825
TI  - A miniaturized artificial mastoid using a skull simulator.
AB  - A miniaturized artificial mastoid of size and weight that allow calibration and
      measurement of bone conduction hearing aids in a conventional audiometric
      soundproof box has been developed. Its level of mechanical impedance corresponds
      to the standard IEC 373 (1990) within the frequency range 250 Hz to 8 kHz. The
      miniaturized artificial mastoid consists of three parts: coupler, skull simulator
      (TU-1000), and an external electrical correction filter. The coupler is a highly
      damped mass-spring system designed to give the miniaturized artificial mastoid
      mechanical impedance in accordance with the standard IEC 373 (1990). It was found
      that the miniaturized artificial mastoid yielded results that are in
      correspondence with results obtained with the Bruel & Kjaer type 4930 artificial
      mastoid for frequencies above 450 Hz. Thus, at these frequencies, the
      miniaturized artificial mastoid can be used for audiometer calibration as well as
      measurement of bone conduction hearing aids.

PMID- 9638826
TI  - Influence of electrode position on near-threshold recording of auditory evoked
      brainstem potentials.
AB  - Use of brainstem potentials in audiology is based on identifying a response in
      the near-threshold range. Wave V has turned out to be the component of the
      brainstem potentials that can be detected with a great deal of reliability when
      assessment of the threshold for the particular stimulus is desirable. As the
      detection of Wave I can be dispensed within audiologic diagnosis, the question
      arises as to whether or not a non-cephalic reference electrode compared to the
      common lateral position of the reference electrode on the ipsilateral mastoid
      produces a more stable Wave V of increased amplitude. In a group of 20 normal
      hearing adults, near-threshold stimulation with clicks was conducted and the
      brainstem potentials recorded simultaneously with the reference electrode placed
      in four different locations (ipsilateral mastoid, contralateral mastoid, non
      cephalic electrode, and ipsilateral earlobe). At all of the three intensities
      studied (10 dB nHL, 20 dB nHL and 30 dB nHL), recording with the non-cephalic
      reference yielded the highest amplitudes, the finding being statistically
      significant.

PMID- 9638827
TI  - Auditory function in 70- and 75-year-olds of four age cohorts. A cross-sectional
      and time-lag study of presbyacusis.
AB  - Within the framework of the gerontological and geriatric population studies in
      Goteborg, Sweden, 473 elderly persons were examined using pure-tone audiometry in
      two recent cohorts. The aim of this study was to present cross-sectionally
      acquired hearing data in these contemporary groups aged 70 and 75. Another
      objective was to compare hearing function at the same age over the last two
      decades (time-lag study) in three 70-year-old cohorts and three 75-year-old
      cohorts. The largest time-lags were 14 years (75-year-olds) and 21 years (70-year
      olds). The most recently tested cohort of 70-year-olds, studied in 1992,
      demonstrated median pure-tone averages (PTA: 0.5, 1 and 2 kHz) of 20.2 dB HL in
      the left ear of men and 18.2 dB HL in women. The left median pure-tone thresholds
      at 4 kHz were 56.0 dB HL in men and 34.7 dB HL in women. Hearing acuity in 70
      year-olds was not demonstrated to have changed in any consistent fashion over a
      21-year time-lag. For the most recently evaluated 75-year-olds, the median PTA in
      the left ear was 27.3 dB HL in men and 21.6 dB in women. The left median 4 kHz
      threshold was 67.3 in the male group and 45.5 dB HL in the female group. Hearing
      in 75-year-olds over a time-lag of 14 years demonstrated somewhat better pure
      tone thresholds predominantly in the men's better ear in the earliest cohort when
      compared to the cohort tested in 1990-91. However, there were no consistent
      differences of pure-tone thresholds between these age cohorts, except for the
      intermediate cohort 2, in which the men had generally worse hearing. Thus, there
      was no apparent evidence of changes of the auditory function in elderly of the
      same age over the last two decades. Gender-specific dissimilarities in annual
      pure-tone threshold deterioration between the ages of 70 and 75 were found and
      are discussed.

PMID- 9638828
TI  - Epidemiology of moderate to profound childhood hearing impairments in northern
      Finland. Any changes in ten years?
AB  - The epidemiology of childhood hearing impairments was studied in a clinical
      series of the birth cohorts for 1973-82 and 1983-92 from a geographically well
      defined area. The overall prevalence of hearing impairments with PTA0.5-4 kHz >
      or = 40 dB was 1.2/1000 live births. Even in the later cohort, the median age
      ascertainment was 2.6 years for the congenital or early acquired group and 3.0
      years for all impairments. Risk indicators for hearing impairment were present in
      half of the children, and those referred for the risk were ascertained at the
      median age of 1.1 years. The delay from suspicion to ascertainment was over a
      year in about one fifth of cases, while the median time from referral to
      ascertainment was only 1.8 months. The planning and implementation of neonatal
      hearing screening are suggested, and general information is given on
      paedoaudiology for both parents and professionals. A database could be beneficial
      in increasing the systemacy of the diagnostic process.

PMID- 9638829
TI  - Equivalent threshold sound pressure levels for Sennheiser HDA 200 earphone and
      Etymotic Research ER-2 insert earphone in the frequency range 125 Hz to 16 kHz.
AB  - Equivalent Threshold Sound Pressure Levels (ETSPLs) have been determined for the
      Sennheiser HDA 200 earphone and the Etymotic Research ER-2 insert earphone.
      Thirty-one young normal-hearing test subjects participated and the thresholds
      were determined for all recommended frequencies in the frequency range 125 Hz to
      16 kHz. The results for the HDA 200 earphone are generally in very good agreement
      with the results from two other investigations which are available at present.
      Only at 6 kHz is a 9 dB deviation found and at 8 kHz a 6 dB deviation is found
      between the three investigations. For ER-2 it has not been possible to find other
      ETSPL determinations in the literature.

PMID- 9638830
TI  - Agreement between two tympanometers. A methodological study of instrument
      comparison.
AB  - When old instruments are replaced by new ones, agreement between them becomes
      important when comparing measurements. Their precision, too, is important. A
      common, however inappropriate, statistical approach in these cases is correlation
      analysis. As an alternative, a simple statistical method is suggested, in which
      differences between measurements of either instrument are plotted against their
      means. The distribution of the differences is tested against 0 (one-sample t
      test), and for good agreement P > 0.05. This statistical method was used in a
      group of 32 adults in which measurements taken with an older automatic
      tympanometer and a new digital one were compared. Static compliance and and
      gradient showed good agreement, while middle ear pressure showed a significant
      bias between instruments explained by phase delay. This disagreement was
      insignificant for clinical purposes, but may be important in scientific studies.
      The same statistical principle applies determining the precision of each
      instrument. The new digital instrument showed higher precision than the older
      one.

PMID- 9638831
TI  - Normative Wave V latency-intensity functions using the EARTONE 3A insert earphone
      and the Radioear B-71 bone vibrator.
AB  - Early auditory evoked response (ABR) audiometry is useful for estimating auditory
      sensitivity in infants and other difficult-to-test populations. Several
      investigations advocate using bone-conducted stimuli, in addition to air
      conducted stimuli, for screening infants with hearing loss or for ascertaining
      the presence and magnitude of a conductive hearing loss. The present study was
      designed to gather normative Wave V latency-intensity data with an insert
      earphone (EARTONE 3A) and a bone vibrator (Radioear B-71). Forty normal-hearing
      subjects were tested with air-conducted and bone-conducted clicks at intensities
      of 55, 40, 30, 20, and 10 dB SL. The stimulus waveforms showed a click onset
      delay of 0.1 ms for the 3A insert earphone. It is important to note that our ABR
      latencies were not adjusted to account for these differences. The results
      revealed that both the air-conduction and bone-conduction functions exhibited
      Wave V latencies of 7.0 ms at 55 dB SL. Although both functions exhibited
      increased latencies as intensity decreased to 10 dB SL, the air-conducted clicks
      yielded somewhat longer latencies than the bone-conducted clicks. To allow direct
      comparison of the air-conduction and bone-conduction latency-intensity function,
      the bone-conduction function must be corrected by approximately +0.3 ms at 40 dB,
      +0.4 ms at 30 dB, +0.5 ms at 20 dB, and +0.8 ms 10 dB nHL. No correction is
      needed at 55 dB. The present study suggests that it may not be appropriate to
      apply a single correction value (e.g., 0.5 ms) to the entire latency-intensity
      function. If clinicians elect to use published latency-intensity data, they must
      employ procedure similar to those that were used to collect the normative data.
      Otherwise, individual clinics should generate normative latency-intensity data
      using well-defined procedures. An alternative to generating latency-intensity
      functions is to compare ABR air-conduction and bone-conduction thresholds. This
      procedure is advantageous because threshold responses are not as sensitive as
      latency measures to slight changes in instrumentation and procedures. The
      normative air-conduction and/or bone-conduction values presented in this
      investigation are offered as a baseline for either latency-intensity or threshold
      comparisons.

PMID- 9638832
TI  - Anterior versus posterior, and rim-rent rotator cuff tears: prevalence and MR
      sensitivity.
AB  - PURPOSE: To determine the relative distribution of the locations of rotator cuff
      tears, and the sensitivity of anterior versus posterior tears on MR images.
      PATIENTS AND METHODS: We identified 110 consecutive patients who had a shoulder
      MR and either a partial-thickness or a small full-thickness rotator cuff tear
      diagnosed at arthroscopy. From the arthroscopy videotapes, we classified the
      tears as centered in the anterior or posterior half of the cuff, and as either in
      the critical zone or adjacent to the bony insertion. The original MR
      interpretation was compared with the arthroscopic findings. MR sensitivity and
      patient age were compared between patients with tears in the anterior and
      posterior halves of the cuff. In addition, in patients with partial tears less
      than 2 cm in diameter, an age comparison between those with tears in the critical
      zone and those with articular surface tears adjacent to the bony insertion (rim
      rent tear) was performed. RESULTS: The tear was centered in the anterior half of
      the rotator cuff in 79% of the patients younger than 36 years old, and in 89% of
      the patients 36 years old and over. The average age of the patients with tears in
      the anterior half (44 years) was not significantly different from the average age
      of those with posterior tears (40 years) (P = 0.23). The sensitivity of MR for
      anterior tears was 0.69, and for posterior tears it was 0.56 (P = 0.17). The
      average age of the 9 patients with rim-rent tears was 31 years, while that of the
      28 patients with similarly-sized partial tears not involving the insertion was 40
      years old (P = 0.048). Five of the nine rim-rent tears (0.56) were interpreted
      correctly on the original MR report; two of the other tears were misinterpreted
      as intratendinous fluid but were diagnosable in retrospect. CONCLUSION: Even in
      patients less than 36 years old, most partial and small full-thickness rotator
      cuff tears are centered in the anterior half of the supraspinatus. Although our
      figure for MR sensitivity for these tears is lower than in recent articles, we
      found no significant difference between the sensitivity of MR for diagnosing
      posterior tears versus tears in the anterior half of the supraspinatus tendon.
      Rim-rent tears can be mistaken for intratendinous signal, and should be carefully
      looked for in younger patients with shoulder pain.

PMID- 9638833
TI  - MRI of fractures of the distal radius: comparison with conventional radiographs.
AB  - OBJECTIVE: To compare the evaluation of fractures of the distal radius with MRI
      and conventional radiographs. To demonstrate the ability of MRI to detect
      unsuspected soft tissue derangement accompanying this common injury. DESIGN AND
      PATIENTS: Twenty-one consecutive inpatients admitted following fracture of the
      distal radius underwent preoperative evaluation with both conventional
      radiographs and MRI. In each case, analysis was made of both the osseous and soft
      tissue injury. MRI findings were compared with those identified on conventional
      radiographs and at subsequent surgical fixation. RESULTS: Of 21 patients with
      fractures of the distal radius, 20 had extension to the radiocarpal articulation,
      14 had distal radio-ulnar joint extension and 5 had avulsion of the ulnar
      styloid. Occult carpal bone fractures accompanying fracture of the distal radius
      were identified in two patients: one of the capitate and the other of the second
      metacarpal base. Ten patients (48%) had associated soft tissue injury: six
      patients had scapholunate ligament rupture, two patients had disruption of the
      triangular fibrocartilage, one patient had extensor carpi ulnaris tenosynovitis
      and one patient had a tear of a dorsal radiocarpal ligament. Of five patients
      with ulnar styloid avulsions, none had evidence of triangular fibrocartilage
      tears. CONCLUSION: MRI affords better evaluation of osseous injury accompanying
      distal radial fractures than conventional radiographs. Intra-articular soft
      tissue injury accompanies distal radial fractures in almost 50% of cases.
      Scapholunate ligament disruption commonly accompanies intraarticular fracture
      through the lunate facet of the distal radius. Fracture of the ulnar styloid is
      infrequently associated with tear of the triangular fibrocartilage.

PMID- 9638834
TI  - MRI of pediatric growth plate injury: correlation with plain film radiographs and
      clinical outcome.
AB  - PURPOSE: To evaluate pediatric growth plate injuries with conventional
      radiographs and magnetic resonance imaging (MRI). To review potential clinical
      impact of MRI on subsequent patient management and outcome. METHODS: Fourteen
      patients with known or suspected growth plate injury were studied. Each patient
      underwent imaging by conventional radiography and MRI within 2 weeks of injury.
      Findings on conventional radiographs and on MR images were compared and then
      correlated with subsequent management and outcome at a mean of 12 months.
      RESULTS: Direct visualization of cartilage afforded by MRI improved evaluation of
      growth plate injury in each case. MRI changed Salter Harris classification or
      staging in 2 of 9 patients with fractures visualized on conventional radiographs,
      allowed the detection of radiographically occult fractures in 5 of 14 cases, and
      resulted in a physical change in management in 5 of the 14 patients studied.
      CONCLUSION: MRI has an important role in the evaluation of acute pediatric growth
      plate injury, particularly when diagnostic uncertainty persists following the
      evaluation of conventional radiographs. MRI allows detection of occult fractures,
      may alter Salter Harris staging, and in the reported study it frequently resulted
      in a change in patient management.

PMID- 9638835
TI  - Value of arthrography after supination trauma of the ankle.
AB  - OBJECTIVE: To investigate the merits of arthrography after supination trauma of
      the ankle. DESIGN AND PATIENTS: In a group of 160 consecutive patients operative
      exploration was performed in cases where arthrography and/or a delayed physical
      examination showed positive findings. In all patients arthrography was performed
      within 48 h after trauma. To determine interobserver agreement, all arthrograms
      were independently evaluated by two radiologists, both ignorant of the first
      assessment. RESULTS: The prevalence of an ankle ligament lesion was found to be
      76%. Of the 122 patients with a rupture of one or more ankle ligaments, 52% had
      an isolated anterior talofibular ligament lesion, 3% had an isolated
      calcaneofibular ligament lesion, and 45% had combined lesions. The site of the
      lesion was predominantly intraligamentous. In the determination of the presence
      or absence of an ankle ligament lesion, the specificity and sensitivity of the
      ankle arthrogram were 71% and 96% respectively. Interobserver agreement on the
      arthrogram was very good (kappa 0.9). In 1% of patients a clear diagnosis was not
      possible by means of arthrography. CONCLUSION: Arthrography provides information
      of high diagnostic quality with excellent interobserver agreement and therefore
      remains the gold standard for early diagnosis (within 48 h) of a lateral ankle
      ligament rupture.

PMID- 9638836
TI  - Synovial effusion in reflex sympathetic dystrophy: an additional sign for
      diagnosis and staging.
AB  - PURPOSE: To improve the present MRI criteria for diagnosis and staging of reflex
      sympathetic dystrophy (RSD) by including increased joint fluid as an additional
      MRI sign of RSD. DESIGN AND PATIENTS: One hundred and fourteen extremities (69
      affected and 45 contralateral controls) in 57 consecutive patients with RSD were
      evaluated using a 1.5-T unit. T1- and T2-weighted pulse sequences, often with fat
      suppression, were used before and after administration of intravenous contrast
      enhancement (Gd). Following T2-weighted image digitization the volume of synovial
      fluid was measured with a computer model. RESULTS: Effusions were detected in 61%
      of the extremities suspected of RSD and in 44% of the contralateral control
      joints. The mean fluid quantity measured in the symptomatic articulation was 201
      mm3. MRI diagnosis of RSD based on previously described criteria was done in 62%
      of the patients, yielding a sensitivity of 60%. Effusions were present in 79% of
      the false negative MRI cases. Retrospectively considering the presence of fluid
      as a potential positive criterion for RSD increases the sensitivity by 31% (to
      91%). CONCLUSIONS: Joint effusions are probably associated with early stages of
      RSD. Adding effusion to the list of radiological criteria for RSD increases the
      sensitivity of MRI from 60% to 91%.

PMID- 9638837
TI  - Subcutaneous granuloma annulare: radiologic appearance.
AB  - OBJECTIVE: Granuloma annulare is an uncommon benign inflammatory dermatosis
      characterized by the formation of dermal papules with a tendency to form rings.
      There are several clinically distinct forms. The subcutaneous form is the most
      frequently encountered by radiologists, with the lesion presenting as a
      superficial mass. There are only a few scattered reports of the imaging
      appearance of this entity in the literature. We report the radiologic appearance
      of five cases of subcutaneous granuloma annulare. DESIGN AND PATIENTS: The
      radiologic images of five patients (three male, two female) with subcutaneous
      granuloma annulare were retrospectively studied. Mean patient age was 6.4 years
      (range, 2-13 years). The lesions occurred in the lower leg (two), foot, forearm,
      and hand. MR images were available for all lesions, gadolinium-enhanced imaging
      in three cases, radiographs in four, and bone scintigraphy in one. RESULTS:
      Radiographs showed unmineralized nodular masses localized to the subcutaneous
      adipose tissue. The size range, in greatest dimension on imaging studies, was 1-4
      cm. MR images show a mass with relatively decreased signal intensity on all pulse
      sequences, with variable but generally relatively well defined margins. There was
      extensive diffuse enhancement following gadolinium administration. CONCLUSION:
      The radiologic appearance of subcutaneous granuloma annulare is characteristic,
      typically demonstrating a nodular soft-tissue mass involving the subcutaneous
      adipose tissue. MR images show a mass with relatively decreased signal intensity
      on all pulse sequences and variable but generally well defined margins. There is
      extensive diffuse enhancement following gadolinium administration. Radiographs
      show a soft-tissue mass or soft-tissue swelling without evidence of bone
      involvement or mineralization. This radiologic appearance in a young individual
      is highly suggestive of subcutaneous granuloma annulare.

PMID- 9638838
TI  - Skeletal age assessment in children and young adults: comparison between a newly
      developed sonographic method and conventional methods.
AB  - OBJECTIVE: To compare the performance of a new sonographic (US) method of bone
      age estimation with other methods currently in use. DESIGN AND PATIENTS: One
      hundred and fifteen subjects underwent left hand/wrist radiography and US
      examination of the hip for bone age assessment. For each patient, measurements of
      skeletal age were available based on Greulich-Pyle and Tanner and Whitehouse, the
      latter being presented in three subtypes (RUS, carpals, and B20) in addition to
      the US values. To assess agreement between methods, each method was compared with
      every other method. Differences between calculated skeletal age and chronological
      age were assessed, and the sensitivity, specificity, and predictive values of
      each method computed. RESULTS: Coupled B20/RUS values showed the best agreement,
      with 95% of observations within 2.45 years of each other, followed by
      carpals/B20, B20/GP, and GP/RUS. The US method agreed the least (difference of
      4.19-5.13 years) with the other methods. The US method provided 85.8% (US vs RUS)
      to 91.3% (US vs GP) concordant results in recognizing differences between
      skeletal and chronological age, and showed a 72.5% sensitivity and a 56.8%
      specificity. CONCLUSION: Although the US method promises to permit a safe and
      cost-effective assessment of skeletal age, its low accuracy makes it currently
      unsuitable for clinical use.

PMID- 9638839
TI  - Polyostotic fibrous dysplasia associated with intramuscular myxomas: Mazabraud's
      syndrome.
AB  - Mazabraud's syndrome, though uncommon, is reported increasingly frequently. It
      represents an entity readily recognisable radiologically on MR imaging. Awareness
      of the syndrome, particularly when the myxoma is solitary, can prevent
      misdiagnosis of intramuscular myxomas (especially when large) as malignant
      mesenchymal tumors containing myxoid tissue. We review the 34 cases previously
      reported in the literature and include a recent case from our center.

PMID- 9638840
TI  - Focal myositis.
AB  - Focal myositis is a pseudotumor of soft tissue that typically occurs in the deep
      soft tissue of the extremities, and is a relatively rare lesion. There is a wide
      clinical spectrum, with approximately one-third of patients with focal myositis
      subsequently developing polymyositis, and clinical symptoms of generalized
      weakness, fever, myalgia, and weight loss, with elevation of creatine
      phosphokinase. We report the case of a patient with focal myositis who
      subsequently developed myositis ossificans-like features.

PMID- 9638841
TI  - Tibial plateau erosions associated with lateral meniscal cysts.
AB  - Although meniscal cysts are common, erosions of bone caused by these cysts are
      quite rare. We report MR imaging findings of two cases in which lateral meniscal
      cysts resulted in erosion of the lateral tibial plateau.

PMID- 9638842
TI  - Condensing osteitis of the clavicle in a man.
AB  - Condensing osteitis of the clavicle is a rare, benign, usually painful condition
      leading to sclerosis of the medial end of the clavicle. In the English language
      literature, this has only been reported in women since its original description
      by Brower et al. in 1974 [1]. We report a clavicular lesion occurring in a man
      that is clinically, radiographically, and histologically identical to described
      cases of condensing osteitis.

PMID- 9638843
TI  - Schnitzler's syndrome.
AB  - We report on a case of Schnitzler's syndrome, focusing on pattern of bone
      involvement and its differential diagnosis.

PMID- 9638844
TI  - Dual renal grafts: expansion of the donor pool from an overlooked source.
AB  - This is a review of the emerging practice of dual renal allografting. In the
      setting of the expanded criteria cadaveric (and usually older) donor with
      inadequate function to allow single kidney transplantation, both kidneys have
      been transplanted into a single recipient. The recipient and donor have often
      been matched for age and size as dictated by the concept of nephron dosing. The
      reported results of dual grafting are excellent and statistically comparable to
      contemporaneous single cadaveric grafts. Criteria are evolving regarding when to
      apply single or dual grafting. Wider acceptance of dual renal grafting could have
      a significant impact on the cadaver kidney shortage.

PMID- 9638845
TI  - Intragraft cytokine gene expression: implications for clinical transplantation.
AB  - As our knowledge of the cytokine network in experimental transplant models grows,
      we need to understand how and to what extent cytokines mediate the various donor
      directed immune events in clinical situations. This overview of clinical cytokine
      measurements shows that specific intragraft cytokine messenger RNA (mRNA)
      expression profiles can be associated with acute rejection, that they may reflect
      the efficacy of immunosuppression, and that they can identify patients at risk
      for the development of early chronic rejection. The literature also shows that
      acute rejection and immunological quiescence in humans are not restricted to the
      cytokine patterns defined in the type 1/type 2 paradigm. This apparent lack of
      association may be caused by the immunosuppression used in the clinic but may
      also be the result of the infinite diversity of donor and recipient factors, in
      which polymorphisms in cytokines and cytokine receptor genes may play a central
      role.

PMID- 9638846
TI  - A comparative study of FK506 granules and capsules in renal transplant
      recipients.
AB  - Nine renal transplant recipients in stable systemic condition on FK506 capsules
      were converted to FK506 granules in order to investigate the safety, efficacy,
      and pharmacokinetics of the granular formulation of FK506. The study period for
      the administration of FK506 granules was 4 weeks, and in principle, the oral dose
      was the same as that of the FK506 capsules. Renal graft function remained stable
      and no rejection signs were noticed while the patients were taking the granules.
      The area under the blood concentration-time curve (AUC), the maximum blood level
      (Cmax), and the time to reach Cmax (Tmax) after FK506 capsules and FK506 granules
      were, respectively, 93.1 +/- 66.4 and 97.0 +/- 89.1 ng.h/ml (P = 0.81), 12.7 +/-
      7.1 and 15.2 +/- 11.7 ng/ml (P = 0.39), and 2.0 +/- 1.7 and 1.3 +/- 0.6 h (P =
      0.29). The mean trough blood level during FK506 medication was 4.25 +/- 3.42 and
      4.02 +/- 3.83 ng/ml, respectively, for the capsules and the granules. FK506
      granules, a new formulation, showed an efficacy comparable to that of the FK506
      capsular formulation.

PMID- 9638847
TI  - Donor pretreatment with ambroxol or dexamethasone fails to ameliorate reperfusion
      injury in experimental lung transplantation.
AB  - Based on the known properties of ambroxol and dexamethasone to inhibit
      inflammation and increase endogenous surfactant levels, the potential advantage
      of donor pretreatment with either drug was investigated in an acute rat double
      lung transplant model. Donor animals were randomly assigned to one of three
      treatment groups: an ambroxol group (AMB; 0.4 mg/kg), a dexamethasone group (DX;
      2 mg/kg); or an untreated control group (CN). Drugs were given intraperitoneally
      6 h prior to harvest. Following standard preservation and 16 h of cold ischemia,
      the donor double lung block was implanted into syngeneic recipients using custom
      designed stents for the vascular anastomosis. During reperfusion, serial
      measurements of graft pulmonary vascular resistance and alveolar-arterial oxygen
      difference were obtained. Separate graft ventilation allowed determination of
      graft dynamic lung compliance. Final assessment included weight gain and
      histology. For phospholipid analysis, lung lavages were performed in the three
      study groups at the end of reperfusion and compared to levels before graft
      harvest. Donor pretreatment did not significantly affect preharvest phospholipid
      levels. Survival following graft ischemia and reperfusion was shortest after AMB
      (92 +/- 5 min) and longest after DX (110 +/- 5 min; DX vs AMB P < 0.03) and CN
      (116 +/- 4 min; CN vs AMB P < 0.02). DX pretreatment provided better compliance
      (P < 0.02) and lower vascular resistance (P < 0.0001) than AMB treatment. Airway
      resistance was lower in the AMB and DX groups than in controls (P < 0.04 and P <
      0.02, respectively). The alveolar-arterial oxygen difference was markedly similar
      in all groups. Graft weight gain amounted to 114% +/- 10% in AMB, 88% +/- 12% in
      DX, and 98% +/- 13% in CN (P = NS). Thus, in this rat lung transplantation model,
      donor pretreatment with dexamethasone did not improve graft function compared to
      untreated controls and donor pretreatment with ambroxol was found to be
      potentially detrimental to graft function during reperfusion.

PMID- 9638848
TI  - Allogenic grafting of vascularized bone segments under immunosuppression.
      Clinical results in the transplantation of femoral diaphyses.
AB  - Trauma surgery lack, substitute, for the reconstruction of large defects of the
      long bones. Encouraged by the promising results of bone allotransplantation in
      animal models, we successfully performed vascularized bone transplantation in
      humans. Vascularized femoral diaphyses were allogenically transplanted into three
      patients suffering from chondrosarcoma or post-traumatic osteomyelitis with
      postoperative immunosuppression. The bone segments were harvested from multi
      organ donors and perfused with UW solution. After back-table preparation, the
      grafts were transplanted into the defect zone. Interlocking devices were used in
      these operations. Vascular anastomoses were performed in end-to-side technique.
      The early clinical course of the patients was not free of anatomical, technical,
      or immunological complications. However, all patients are currently free of
      malignancy and infection. They are also free of pain and full weight bearing. We
      conclude that allogenic grafting of vascularized bone segments has the potential
      to become an alternative for the replacement of large bone defects.

PMID- 9638849
TI  - Single centre experience with mycophenolate mofetil for refractory rejection in
      cadaveric renal transplantation.
AB  - Ten patients with refractory rejection following renal transplantation were
      treated with mycophenolate mofetil (MMF) in an attempt to salvage the allografts.
      All cases of rejection were biopsy-proven. Seven of the patients had initially
      been on tacrolimus-based triple therapy and three were on cyclosporin-based
      regimens. Those on cyclosporin had been unsuccessfully converted to tacrolimus
      prior to receiving MMF. All patients had received at least one course of
      methylprednisolone pulse therapy and three had been given OKT3 prior to MMF. MMF
      was prescribed at a dose of 2000 mg per day in two divided doses and was given in
      addition to tacrolimus and prednisolone. Eight of the ten patients showed
      evidence of reversal of rejection, as indicated by improvement in renal function
      following commencement on MMF, whilst two patients experienced ongoing rejection
      and underwent graft nephrectomy. One of the patients successfully treated has
      since had his MMF discontinued due to gastrointestinal intolerance. We conclude
      that MMF is effective in salvaging renal allografts with resistant rejection and
      that it has an acceptable side-effect profile.

PMID- 9638850
TI  - Optimal pH for simple cold storage or machine perfusion of dog kidneys with UW
      solution.
AB  - Metabolic suppression by temperature is a key to successful organ preservation.
      Additional methods for inducing metabolic suppression may further improve organ
      preservation. Extracellular acidosis has been shown to suppress warm anoxic
      injury to various isolated cells. Acidosis may suppress enzymes with a pH optimum
      at the pH of the cytosol (pH 7.3). In this study, the combination of hypothermia
      and acidosis was used to determine if it would improve renal preservation. Dog
      kidneys were cold-stored (CS) for 48 h in University of Wisconsin (UW) solution
      with the pH adjusted to 6.4, 6.8, 7.4, or 7.8. Kidneys were also machine-perfused
      (MP) for 3 days with the gluconate perfusion solution (Belzer's machine perfusion
      solution, MPS) at pHs similar to those tested for CS. Renal function (serum
      creatinine, SCr) and survival were recorded in immediate contralateral
      nephrectomized recipients. On the basis of maximum SCr values, kidneys preserved
      by CS or MP were best preserved at pHs of 7.4 or 7.8. At a pH of 6.8, SCr values
      were elevated and returned to normal at a slower rate than in those preserved at
      higher pHs. This study shows that acidosis is not cytoprotective to cold-stored
      dog kidneys and causes preservation/reperfusion injury.

PMID- 9638851
TI  - Situs inversus of donor or recipient in liver transplantation.
AB  - Situs inversus is a rare anatomical abnormality that is often associated with
      multiple, complex malformations. In the past, patients with situs inversus were
      considered unsuitable candidates for transplantation or organ donation because
      associated visceral, and especially vascular, anomalies pose special technical
      difficulties. Recently, several cases of successful liver transplantation in
      recipients with situs inversus have been published using modified surgical
      techniques. This report reviews the literature and describes our own experience,
      including two liver graft recipients with complete and incomplete situs inversus,
      and one patient who underwent successful transplantation using a liver from a
      donor with situs inversus.

PMID- 9638852
TI  - A validated technique for the analysis of biliary bile acid secretion in donor
      livers prior to transplantation.
AB  - Many parameters currently used for the pre-transplant assessment of liver
      allografts, are not reliable enough in predicting the likelihood of early graft
      dysfunction or non-function. It is generally accepted that bile secretion is a
      sign of hepatic function post-transplant and that bile flow shows a close linear
      relationship to the secretion of bile acids ("apparent choleretic activity"). We
      have studied bile flow, biliary bile acid concentrations and composition and
      measured apparent choleretic activity from hepatic bile collected with a new
      technique under controlled conditions at the time of retrieval from 18 donor
      livers. More than three samples were collected from each of 13 donors and a total
      of 65 samples of hepatic bile were analysed. Of these, ten showed typical
      apparent choleretic activity with a positive slope in the regression line
      analysis (correlation coefficient of 0.9), validating our collection technique.

PMID- 9638853
TI  - High-Na+ low-K+ UW cold storage solution reduces reperfusion injuries of the rat
      liver graft.
AB  - The isolated perfused rat liver model was used to assess graft viability after 24
      h of cold preservation. Two solutions were compared for liver preservation:
      Belzer's original UW solution (high-K+ UW) and a solution containing the same
      components but with inverted concentrations of sodium and potassium (high-Na+
      UW). During the 120 min of normothermic reperfusion, livers preserved in the high
      Na+ UW solution released lower levels of creatine kinase-BB isoenzyme,
      transaminases (ALT and AST), and potassium than those preserved in the high-K+ UW
      solution. Bile flow and biliary excretion of indocyanine green increased when
      livers were preserved in the high-Na+ UW solution. We found no statistical
      differences for oxygen consumption and tissue ATP concentration. The results of
      this study support the concept that a high-Na+ UW solution is a more effective
      means of preserving rat livers, at least after 24 h of cold-storage and 120 min
      of reperfusion in the isolated perfused model, than the original high-K+ UW
      solution. Liver preservation in the high-Na+ UW solution reduces damage to
      sinusoidal endothelial and hepatocellular cells. The use of an extracellular-like
      Belzer cold storage solution eliminates potassium-related problems in cold
      preservation and subsequent normothermic reperfusion while keeping all the
      qualities of the original UW solution.

PMID- 9638854
TI  - A randomized prospective study comparing low-dose OKT3 to low-dose ATG for the
      treatment of acute steroid-resistant rejection episodes in kidney transplant
      recipients.
AB  - Acute steroid-resistant rejection episodes in kidney allograft recipients require
      treatment with antilymphocyte antibodies. Monoclonal anti-CD3 and polyclonal
      antilymphocyte antibodies have been widely used but seldom compared. Recent data
      have suggested that these antibodies could be used at reduced doses without
      jeopardizing their efficacy. In this study, we randomized renal transplant
      recipients who encountered a first acute steroid-resistant rejection episode to
      low-dose ATG or low-dose OKT3 treatment. Sixty patients were enrolled in the
      study. They received prophylactic immunosuppression with cyclosporin,
      azathioprine, and prednisolone. Treatment of biopsy-proven rejection consisted of
      a 10-day course of either ATG (n = 31) or OKT3 (n = 29). The total ATG dose was
      484 +/- 110 mg, i.e., 0.75 mg/kg per day. The total OKT3 dose was 32 +/- 4 mg,
      i.e., 0.05 mg/kg per day. We compared reversion of rejection, side effects,
      immunodepression, and graft function. Reversion of rejection was similar in the
      two groups, although we noted a trend in favor of ATG. Results were 3% vs 10%
      early graft failures, 13% vs 23% overall graft failures, 28% vs 38% 3-month
      actuarial incidence of rebound rejection, and 89% vs 81% 1-year graft survival
      rate in the ATG and OKT3 groups, respectively. Tolerance was worse in the OKT3
      group due to the first-dose syndrome. Infections and cancers occurred with the
      same frequency. ATG resulted in a deeper and longer decrease in peripheral
      lymphocyte subsets. Graft function was similar in the two groups. We conclude
      that low-dose ATG and low-dose OKT3 are equally effective in reversing steroid
      resistant acute rejection. Tolerance was better with ATG, which also gave a more
      potent and longlasting immunodepression. The use of reduced doses of ATG and OKT3
      did not appear to lessen their efficacy.

PMID- 9638855
TI  - Bradycardia in children less than two years of age during liver transplantation.

PMID- 9638856
TI  - Prevention of ischemic injury in the small intestine.

PMID- 9638857
TI  - Report of the Second Equine Leucocyte Antigen Workshop, Squaw valley, California,
      July 1995.
AB  - The final assignment of antibody clusters for leucocyte antigens and
      immunoglobulins, as described in detail in Sections 3 and 4, is summarized in
      Table 4. Together with other mAbs developed outside of ELAW II (Table 9) this
      pool of reagents represent a powerful array of tools for the study of equine
      immunity. The Second Equine Leucocyte Antigen Workshop made considerable advances
      in pursuing the objectives of establishing the specificities of mAbs and
      achieving consensus on the nomenclature for equine leucocyte and immunoglobulin
      molecules. Of equal importance, several productive collaborations were fostered
      among the participating laboratories and observers. Overall, enormous advances
      have been made in the past decade since mAbs specific for equine leucocyte
      antigens and immunoglobulins were first reported. There remains enormous scope
      and need for further studies of equine leucocyte antigens and immunoglobulins,
      both for the purposes of comparative immunology and for the good of the horse. In
      the future novel techniques will be required to develop reagents for specific
      target antigens such as the orthologues of the CD25 or CD45 isoforms. In studies
      of equine immunoglobulins the functional role of the IgG isotypes must be better
      established, reagents for IgE must be developed, and cloning of the
      immunoglobulin heavy chain genes will be essential if the complexities of the IgG
      sub-isotypes are to be elucidated. The tasks still facing the currently small
      group of equine immunologists throughout the world remain formidable, and will
      only be tackled successfully in a spirit of collaboration.

PMID- 9638858
TI  - Production of monoclonal antibodies to six isotypes of horse immunoglobulin.
AB  - Stable clones of 18 mouse hybridomas that produce monoclonal antibodies (MAbs) to
      six isotypes of horse immunoglobulin were produced. The number of hybridomas of
      different specificities are: four to IgGa, four to IgGb, one to IgGc, four to
      IgG(T), two to IgM, and three to IgA. The immunoglobulin isotypes purified from
      affinity columns bound with each MAb showed variable mobility in agarose-gel
      electrophoresis. Migration proceeded from the anode as: IgG(T), IgA, IgM, IgGc,
      IgGb and IgGa. The purified isotypes also demonstrated a single precipitin line
      when in immunoelectrophoresis against isotype-specific or polyclonal antisera,
      raised against the purified isotype or whole equine serum, respectively.

PMID- 9638859
TI  - Monoclonal antibodies to subclass-specific antigenic determinants on equine
      immunoglobulin gamma chains and their characterization.
AB  - This paper describes the production of a panel of monoclonal antibodies (mAbs)
      identifying the four recognised equine IgG subisotypes IgG, IgGa, IgGb, IgGc and
      IgG(T). Pure preparations of the subisotypes for use in immunisations and testing
      were produced using a combination of gel filtration, salt precipitation, ion
      exchange chromatography and protein A and Protein G affinity chromatography. The
      specificity of mAbs for the IgG subisotypes was confirmed using ELISA assays, by
      characterisation of affinity purified proteins recognised by the mAbs, and by
      Western blotting of equine serum proteins. The expression of equine IgG
      subisotypes by B cells was examined by flow cytometry using the panel of mAbs.

PMID- 9638860
TI  - The equine homologue of LFA-1 (CD11a/CD18): cellular distribution and
      differential determinants.
AB  - The equine homologue of the leucocyte integrin LFA-1 (CD11a/CD18) has been
      characterized using a panel of four monoclonal antibodies (mAbs). The antibodies
      labelled almost all leukocytes, thymocytes and lymph node cells from normal
      horses, and immunoprecipitated two noncovalently associated polypeptides with
      molecular weights of 180 kDa and 100 kDa, respectively. The antigen recognized by
      one mAb could be precipitated by another in this cluster in a sequential
      immunoprecipitation assay. The mAbs, however, did not block the activities on
      lymphocyte function of one another. A mAb to the beta subunit of human LFA-1
      cross-reacted with equine LFA-1, but an antibody to its alpha subunit did not,
      suggesting that the beta subunit of the leukocyte integrin may be more highly
      conserved. Functionally, H20A and a human CD18 antibody (MHM23) inhibited phorbol
      ester-mediated homotypic lymphocyte aggregation, whereas mAb CZ3.2 induced rather
      than inhibited the homotypic cell aggregation. The formation of lymphocyte
      aggregates induced by CZ3.2 was not blocked by the inhibitory antibodies H20A or
      MHM23. CZ3.1 seemed to have little inducible or inhibitory effects on homotypic
      cell aggregation. The mAb CZ3.1 defined a unique LFA-1 determinant present on
      granulocytes, but absent on lymphocytes in members of an extended horse family,
      in contrast to the other antibodies which labelled both granulocytes and
      lymphocytes from these animals. In all other horses tested, no differences in
      reactivity of CZ3.1 and the other LFA-1 antibodies were observed when the
      antibodies were tested on lymphocytes or granulocytes. Our results indicate that
      common epitopes are shared' between human and equine LFA-1, and that the
      described panel of monoclonal antibodies identifies distinct determinants present
      on the equine LFA-1 molecule. The following monoclonal antibodies used in this
      study were given official workshop designations at the Second International
      Workshop on Equine Leukocyte Antigens (Lunn et al., 1998) CZ3.1 (Cor) = W45;
      CZ3.2 (Cor) = W77.

PMID- 9638861
TI  - The genome of Staphylococcus aureus: a review.
AB  - The genome of Staphylococcus aureus consists of a single circular chromosome (2.7
      2.8 mbp) plus an assortment of extrachromosomal accessory genetic elements:
      conjugative and nonconjugative plasmids, mobile elements (IS, Tn, Hi), prophages
      and other variable elements. Plasmids (1-60 kbp) are classified into 4 classes
      and there are 15 known incompatibility groups. Mobile elements of the genome (0.8
      18 kbp) appear in the chromosome or in plasmids of classes II and III. Prophages
      (45-60 kbp) are integrated in the bacterial chromosome, and they are UV- or
      mitomycin-inducible. Temperate bacteriophages of S. aureus are members of the
      Siphoviridae and the serological groups A, B and F occur most frequently. In the
      paper presented, the characteristics of chromosome, plasmids, transposons and
      other genetic elements of S. aureus genome are given and an alphabetical list of
      known genes of this species is included.

PMID- 9638862
TI  - Cooperative haemolysis between weakly-beta haemolytic human intestinal
      spirochaetes and Clostridium perfringens.
AB  - Interactions between human intestinal spirochaetes (HIS) related to intestinal
      spirochaetosis and intestinal pathogenic anaerobic bacteria were investigated by
      searching for the presence of cooperative haemolysis among 39 strains of weakly
      beta-haemolytic human intestinal spirochaetes and Clostridium perfringens alpha
      toxin producers on plates carrying six different sheep blood agar media. An area
      of intense cooperative haemolysis (about 3-10 mm) was observed between all tested
      spirochaetal strains and C. perfringens where the clostridial alpha-toxin
      diffused toward the colonies of the spirochaetes overlapping part of their growth
      zone. The cooperative haemolysis was a potentiation of the haemolysis due to the
      single cultivation of human intestinal spirochaetes and C. perfringens and was
      observed after anaerobic incubation for 24-48 hours when both bacteria at a
      concentration range of 10(8)-10(3) CFU/ml were streaked at a distance of 3-10 mm
      to each other. A cooperative haemolysis was also observed between C. perfringens
      and weakly beta-haemolytic spirochaetes related to porcine and avian intestinal
      spirochaetosis and the spirochaete causing swine dysentery. The present study
      indicated that the damage produced in vitro by the clostridial alpha-toxin was
      enhanced only on the red blood cells which were in proximity to the HIS colonies
      causing the complete lysis of the erythrocytes. It is hence possible that the
      potentiation of the damage to red blood cells observed in vitro mimics an in vivo
      damage on the membranes of enterocytes to which HIS are attached when intestinal
      spirochaetosis occurs and when cytolysins similar to the alpha-toxin are
      available in the intestine of the host.

PMID- 9638863
TI  - Electrophoretic characterization of exposed outer membrane proteins in
      environmental and human Bacteroides fragilis strains.
AB  - Bacteriodes fragilis isolated from aquatic environment, from infectious process
      and from human feces were compared as to their outer membrane protein
      electrophoretic profiles after staining with Coomassie blue and reacting with
      antibodies prepared against whole-cell antigens of a reference strain from a
      clinical source. A marked homogeneity was found among the strains with these
      methodologies. The profiles of all strains obtained after radio-iodination of the
      intact cell showed qualitative similarity when compared with the profiles
      obtained by the other methods. Thus, these data allow us to suggest the
      designation of the peptides observed in the autoradiograms as surface-exposed
      proteins. Differences observed in the autoradiograms in the expression of bands
      mainly detected at a molecular weight of 28 in the commensal strain 118,310
      defined previously as avirulent, in addition to a distinction in the titres of
      agglutination with the sera tested and lower reactivity in the immunoblotting
      assays, suggest a relationship of the B. fragilis surface architecture with the
      virulence potential as well as with the origin of the strain.

PMID- 9638864
TI  - Outer membrane proteins of Klebsiella pneumoniae after exposure to ciprofloxacin.
AB  - Suppression of bacterial growth of two Klebsiella pneumoniae strains after a
      short time exposure to ciprofloxacin at suprainhibitory concentrations was found
      (postantibiotic effect-PAE). PAEs induced by ciprofloxacin at 2 x MIC were 4.1 h
      and 5.3 h for the strains tested, the concentration of 4 x MIC manifested a
      suppression of the bacterial growth which lasted 5.9 h and 6.3 h. Delay of
      regrowth of K. pneumoniae strains exposed to suprainhibitory concentrations of
      quinolones was shown also by other authors. New information concerning the outer
      membrane protein profile of K. pneumoniae after PAE has been found. SDS-PAGE
      analysis revealed that outer membrane protein patterns isolated from K.
      pneumoniae strains treated with a suprainhibitory concentration of ciprofloxacin
      did not show apparent changes as compared to controls.

PMID- 9638865
TI  - Detection of Borrelia burgdorferi in urine specimens from dogs by a nested
      polymerase chain reaction.
AB  - A nested PCR (nested flagellin PCR) carrying an internal E. coli DNA control was
      established and compared with an in-vitro culture method for the detection of
      Borrelia burgdorferi in urine specimens of dogs. The predicted specific amplicon
      of the flagellin gene fla was generated from all cultured strains of B.
      burgdorferi tested (comprising three European genospecies). In contrast, all 13
      strains of seven other flagellated bacterial species were negative. The PCR
      detection limit yielded 20 cells of B. burgdorferi per ml of double-distilled
      water and approx. 250 bacteria per ml of dog urine. Using the bacterial culture
      method, urine specimens collected from 216 dogs in Germany were all diagnosed
      negative for spirochetes by in-vitro culture and dark-field microscopy. In
      contrast, DNA of B. burgdorferi was detected in 32 specimens (14.8%) by PCR. 31
      urine specimens (14.4%) showed inhibitory activity in the PCR assay. However, 94
      (44%) were inhibitory in the culture assay. The majority of the PCR-positive dogs
      exhibited major clinical symptoms which have not been reported in the course of
      B. burgdorferi infection previously, e.g. cystitis (14/32 dogs) or prostatitis
      (5/32 dogs). Our results indicate that the analysis of urine specimens by the
      nested flagellin PCR is a highly valuable procedure for the diagnosis of B.
      burgdorferi infections in dogs.

PMID- 9638866
TI  - Comparison of genetic characteristics of MRSA strains present in a Warsaw
      hospital in 1992 and 1996.
AB  - Nine isolates of methicillin-resistant Staphylococcus aureus (MRSA) collected in
      a Warsaw hospital in 1996 were typed by phenotypic (resistograms) and genotypic
      (PFGE and plasmid restriction analysis-REAP) methods. Twenty-four (MRSA) strains
      collected in this hospital during a period of the same duration in 1992 and typed
      earlier using resistograms and PFGE were also typed by REAP. Comparison of typing
      results obtained for isolates from 1992 and 1996 showed that strains
      characterised by PFGE patterns of two distinct types described as specific of the
      two clonally related groups of Polish MRSA in a multicentre study in 1992 are
      continuously present in the hospital. However, MRSA strains representing PFGE
      patterns not observed before were also found within the collection from 1996.
      REAP typing has proved to have a discriminatory power similar to that of PFGE
      analysis. Nevertheless, due to the lack of plasmids or difficulties in plasmid
      DNA isolation in 3 out of 33 studied strains, the typability of REAP turned out
      to be lower than that of PFGE.

PMID- 9638867
TI  - Effect of isoleucine on toxin production by Clostridium difficile in a defined
      medium.
AB  - Supplementation of a carbohydrate-free minimal medium with a high level (100 mM)
      of histidine, methionine, valine, isoleucine, proline and leucine, in particular
      isoleucine, markedly increased toxin production by Clostridium difficile VPI
      10463. The effect of isoleucine was further examined. Increasing the
      concentration of isoleucine from 20 to 100 mM remarkably increased toxin
      production, while bacterial growth decreased gradually. Amino acid analysis of
      the culture revealed that, at 100 mM isoleucine, consumption of isoleucine was
      remarkably increased. During the incubation period when toxin titers increased
      markedly but bacterial growth was declining, isoleucine, leucine and cysteine
      were taken up preferentially and alanine and cystathionine, which were not found
      at 1 mM isoleucine, were produced in large quantities. These findings suggest
      that isoleucine may play an important role in toxin production by C. difficile
      and that alanine and cystathionine production may be co-regulated with the toxin
      production in the absence of fermentable carbohydrates.

PMID- 9638868
TI  - Studies of the presence of the virulence factors, adhesion, invasion,
      intracellular multiplication and toxin formation in salmonellas of different
      origin.
AB  - Salmonellas of different origin were classified into two groups (11 strains of
      common serovars which had been isolated from organs of calves having died from
      salmonellosis and 18 strains belonging to rare serovars which showed uncommon
      metabolic characteristics and had been isolated from spices and spiced foods).
      The strains were examined with regard to different virulence parameters. All
      salmonellas investigated possessed the genetic information on invasion (invA) and
      toxin formation (stn). They adhered equally well to epithelial cells, could
      penetrate into these and survive and multiply inside the cells. The formation of
      toxic substances could be detected in all strains after co-cultivation with
      epithelial cells in the CHO-K1 test. Significant differences between the groups
      of strains could be demonstrated only for the invasion of epithelial cell
      monolayers. Since adhesion, invasion and the ability of intracellular survival
      and multiplication as well as toxin formation constitute virulence parameters of
      salmonellas, it must be assumed that also the Salmonella serotypes studied which
      have been rarely observed epidemiologically constitute a risk for humans.

PMID- 9638869
TI  - Influence of stress conditions on Bacteroides fragilis survival and protein
      profiles.
AB  - Bacteroides fragilis strains isolated from different sources, i.e. 1 strain (AA1)
      from an aquatic environment, 1 strain from normal flora (118310) and the type
      strain (ATCC 25285) originally isolated from clinical material, were analysed for
      both cell envelope proteins composition and surviving under oxidative stress
      starvation. All strains examined showed a similar survival response when cultured
      in drinking water with a ten-fold decrease in viable counts per day during the 7
      days of analysis. The outer membrane protein (OMP) profiles of all strains were
      quite similar during the stress period as determined by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE). However, the periplasmic proteins
      of the strain 118310 showed two protein bands at 48 and 58 kDa, respectively,
      that were absent in the strains AA1 and ATCC 25285 during the incubation period
      in potable water. Whole cells and periplasmic 35S-labelled proteins from bacteria
      cultured in drinking water showed a significant increase in proteins at 16, 18,
      24, 26, 35, 48, and 58 kDa and 18, 22, 24, 48, 58, and 70 kDa, respectively, in
      all strains when compared to cells grown in BHI-PRAS media as detected by
      autoradiography following SDS-PAGE. These data suggest that B. fragilis may have
      a synthesis mechanism that allows them to adapt to adverse environments.

PMID- 9638870
TI  - Activity of silver ions in different media.
AB  - A major problem in medicine is the large number of infections associated with
      implanted and indwelling devices. Silver coating of medical devices is believed
      to preserve infection resistance. Several in vitro and animal studies as well as
      clinical observations on silver-nylon, silver-intramedullary pins, silver-oxide
      Foley catheters and silver-coated vascular protheses have been interpreted as
      successful for the prophylaxis of foreign-body infections. Nevertheless, these
      products have not been established in clinical use. In this study we have been
      able to present physico-chemical and pharmacological data as well as simple
      microbiological experiments explaining the reduced anti-microbial activity of
      silver-ions in some biological fluids.

PMID- 9638871
TI  - Susceptibility of the anaerobic gram-negative non-sporulating rod, Bilophila
      wadsworthia to beta-lactams, beta-lactamase inhibitors, meropenem, metronidazole,
      clindamycin and quinolones.
AB  - The susceptibility of eighty-seven strain of Bilophila wadsworthia to five beta
      lactams, two beta-lactamase inhibitors, meropenem, metronidazole, clindamycin and
      two quinolones was determined. Tests were performed by the modified reference
      agar dilution technique using triphenyltetrazolium chloride for endpoint reading.
      The test strains showed a reduced susceptibility to the beta-lactams, penicillin
      G (MIC90 4 micrograms/ml), ampicillin (MIC90 32 micrograms/ml), piperacillin
      (MIC90 64 micrograms/ml), cephalothin (MIC90 2 micrograms/ml and cefotaxim (MIC90
      4 micrograms/ml). The activity of ampicillin was increased by addition of the
      beta-lactamase inhibitor, sulbactam (MIC90 2 micrograms/ml), as was the activity
      of piperacillin by the addition of tazobactam (MIC90 4 micrograms/ml) 90.8% of
      the strains were found to produce beta-lactamase by the nitrocefin tube method.
      All strains were shown to be highly susceptible to meropenem, metronidazole and
      clindamycin (MICs < or = 1 microgram/ml). Sparfloxacin (MIC90 1 microgram/ml) and
      ciprofloxacin (MIC90 0.5 microgram/ml) were found to be active against most of
      the strains tested.

PMID- 9638872
TI  - Intracerebellar tuberculoma in a patient with AIDS. A case report.
AB  - The incidence of tuberculosis in HIV-infected patients has increased continuously
      over the past ten years. Extrapulmonary manifestations have become more frequent
      in AIDS patients than in immunocompetent hosts. Here we report about a patient
      with an unusual presentation of extrapulmonary tuberculosis. Our case report
      indicates that differential diagnosis of brain lesions in HIV-infected patients
      should include tuberculosis. In uncertain cases, it is indispensable to obtain
      specimens by craniotomy or stereotactic biopsy.

PMID- 9638873
TI  - Virulence factors of Staphylococcus aureus in the pathogenesis of endocarditis. A
      comparative study of clinical isolates.
AB  - It is now generally accepted that adherence of microorganisms to various
      components of cardiac valve surfaces or vegetation lodging on the heart valves is
      an important early event in the pathogenesis of infective endocarditis. 120
      clinical isolates of S. aureus obtained from patients with endocarditis and wound
      infections and from nasopharyngeal carriers were quantitatively analysed in vitro
      for their ability to bind to fibronectin and to produce protein A and alpha
      toxin. Both cell-bound and extracellular protein A were measured and alpha-toxin
      was determined as antigen and as haemolytic activity. The highest fibronectin
      binding ability was found in carrier strains while no significant differences
      between strains were observed regarding the production of protein A. Strains
      isolated from patients with endocarditis produced significantly lower amounts of
      alpha-toxin than did strains from the other two groups. An inverse relationship
      between the production of protein A and of alpha-toxin was noticed in the
      material. Animal passage of five strains in an experimental endocarditis model
      showed a good reproducibility of the test systems and one strain was upregulated
      in its fibronectin binding ability and in alpha-toxin production. These in vitro
      results indicate that the fibronectin binding ability is not the decisive
      adherence factor and question the role of alpha-toxin as a virulence factor in
      endocarditis.

PMID- 9638874
TI  - Cloning and sequencing of BeS-1 gene encoding the immunogenic antigen of
      Streptococcus sanguis KTH-1 isolated from the patients with Behcet's disease.
AB  - In order to analyze the immunopathologic mechanisms of Behcet's disease, the gene
      (bes-1) encoding a streptococcal antigen correlated with the disease was cloned
      and sequenced, and protein produced by this clone was identified by Western
      immunoblotting using serum antibody from the patient. Cellular DNA of
      Streptococcus (S.) sanguis serotype KTH-1 (uncommon serotype 1, strain 113-20)
      from the patient was extracted and digested with EcoRI. The digested fragments
      were cloned into the cloning vector lambda gt11, and then the resulting DNA
      library was immunoscreened using the patient's serum antibody to serotype KTH-1.
      The immunopositive clone of the 1.5 kbp fragment was subcloned into pUC 118
      plasmid (pU8BeS1-1) and sequenced. The sequence showed that the 3'-terminal half
      side region of this insert contained 962bp of open-reading frame (ORF)
      discontinued at the EcoRI restriction site, and the stop codon was not found. The
      nucleotide sequence of the remaining additional 3'-terminal region of this gene
      encoding whole BES-1 was determined by genome walking. The whole ORF of bes-1
      consisted of 849 amino acid residues with a calculated molecular mass of 95 kDa.
      The residues in a portion of the amino acid sequence showed a 60% correspondence
      to those of the human intraocular peptide Brn-3b.

PMID- 9638875
TI  - Binding of immobilized fibronectin by biliary drain isolates.
AB  - Occlusion of biliary stents, as the result of bacterial adhesion and colonization
      onto biliary stents, still remains a major problem. Biliary proteins, such as
      fibronectin (Fn) and vitronectin (Vn), have been presumed to be involved in the
      process of bacterial adhesion to biliary biomaterial. In the present study, Fn
      binding by 5 strains of E. coli isolated from biliary drains or from bile was
      studied. All strains did not bind detectable amounts of soluble Fn but bound to
      immobilized plasma Fn. Adhesion of four strains of E. coli to ovalbumin was
      reduced by periodate treatment of ovalbumin, but adhesion to Fn was unaffected.
      Adhesion was inhibited by mannose-containing saccharides, trypsin treatment of
      the protein, and protease treatment of the bacterial cells. Autoradiography
      showed that components of cell extracts from three E. coli strains bind 125I-Fn
      but not a 150 kD Fn fragment. The findings indicate that the adhesion of these
      bacteria to Fn is a protein-protein interaction, inhibited by D-mannose, and
      possibly mediated by fimbrial components.

PMID- 9638876
TI  - Expression of outer surface proteins A and C of Borrelia afzelii in Ixodes
      ricinus ticks and in the skin of mice.
AB  - Several studies have described changes in the expression of proteins, especially
      of OspA and OspC, of B. burgdorferi sensu stricto during tick feeding. In this
      study, the expression of OspA and OspC of B. afzelii in unfed and feeding I.
      ricinus nymphs and in the subsequent adults was followed by means of the
      immunofluorescence test. Spirochaetes expressing OspA and OspC were observed in
      70% and 80%, respectively of the unfed nymphs. In feeding and in fully engorged
      ticks, spirochaetes expressed OspC, while OspA disappeared 24 hours after the
      beginning of the blood meal. Spirochaetes expressing OspC in salivary glands were
      observed in one engorged tick. After molting, in unfed adults spirochaetes again
      expressed OspA and OspC but did so less frequently (6% and 13%, respectively).
      The mouse strain (AKR/N or BALB/C) on which ticks had their infectious blood meal
      influenced OspC expression in the following tick stage. In the skin of AKR/N
      mice, at the tick feeding site, B. afzelii expressed OspC only, as was shown by
      immunostaining.

PMID- 9638877
TI  - Systemic infection with Yersinia enterocolitica in a hemodialysis patient.

PMID- 9638878
TI  - Cytomegalovirus infection in kidney transplant patients: clinical manifestations
      and diagnosis.
AB  - Cytomegalovirus (CMV) infection is an important cause of morbidity and mortality
      after solid organ transplantation. CMV infection after kidney transplantation was
      confirmed in 19 (54.3%) out of 35 patients. 16 of these (84.2%) developed CMV
      disease. CMV infection was diagnosed based on a fourfold or greater increase of
      anti-CMV IgG antibody titre, detection of CMV-IgM antibodies and/or virus
      isolation. Primary infection was observed in 3 patients, reactivation in 9 and an
      undefined type of infection in 7. In most patients (63%), infection was diagnosed
      in the first 2 months, and in 3 patients, after 3, 5 and 9 years following kidney
      transplantation. The most frequent symptoms of CMV disease were fever (58%),
      pneumonitis (26.3%) and enterocolitis (15.8%). In 53% of the patients, CMV
      infection co-occurred with other pathogens such as Candida albicans. Cryptococcus
      neoformans, bacteria or viruses (HBV, HCV, HSV). Treatment with polyvalent
      globulin (Sandoglobin) or hyperimmune globulin (Cytotect), in combination with
      ganciclovir in 7 patients, resulted in a regression of CMV disease.

PMID- 9638879
TI  - Characterization of pathogenetic determinants of Candida albicans strains.
AB  - The study was an attempt to correlate phenotypic pathogenetic determinants of
      clinical Candida albicans strains with their genotype as determined by PCR
      fingerprinting. A total of 25 C. albicans strains was tested. Adherence capacity,
      hydrophobicity and proteinase production were compared with the genotypes of the
      particular Candida strains. The fungal strains represented eleven genotypes. No
      correspondence relationship was found between genotype and the markers of
      pathogenicity.

PMID- 9638880
TI  - Phage restriction and the presence of small plasmids in Salmonella enteritidis.
AB  - Between 1990-1994, a total of 16,505 S. enteritidis strains of human, animal and
      food origin were phage-typed, using the Hungarian scheme and the changes of
      incidence of the dominant phage types were monitored. The incidence of PT1
      (corresponding to Ward's PT1 was very high between 1990 and 1992 (67.9-71.0% of
      the total S. enteritidis isolates), later, it decreased. The prevalence of PT6
      (corresponding to Ward's PT4) was rare until 1992, then it gradually increased.
      The phage type and plasmid content of 78 Salmonella enteritidis strains were
      determined. Small plasmids were present in 59% of the isolates, together with a
      serotype-specific (38 MDa) plasmid. A correlation was found between the presence
      of the small plasmid and phage restriction to two phages used for subdividing the
      Hungarian phage types 1 (PT1) and 6 (PT6) of S. enteritidis (corresponding to PT1
      and PT4 in Ward's typing scheme, respectively).

PMID- 9638881
TI  - An avian reservoir (Turdus merula) of the Lyme borreliosis spirochetes.
AB  - The reservoir competence of passerine birds for the Lyme borreliosis spirochetes
      was studied in an enzootic focus in Switzerland. Skin aspirates and skin biopsies
      were used to isolate Borrelia spirochetes from Turdus species. B. burgdorferi
      sensu lato was isolated and/or PCR-detected in BSK medium containing skin biopsy
      or skin aspirate from 5 blackbirds (T. merula) and one song thrush (T.
      philomelos). Seven isolates were obtained from 3 different blackbirds. Either B.
      garinii or Borrelia from the genomic group VS116 was found in bird skin samples.
      Mixed infection occurred in 2 cases. Tick xenodiagnosis was used to determine
      whether blackbirds transmitted Borrelia to ticks. Five xenodiagnoses were
      performed on 3 different blackbirds. Borrelia DNA was detected in BSK medium
      inoculated with xenodiagnostic ticks from all the passerines tested. Isolates
      cultured from xenodiagnostic ticks were obtained from 2 blackbirds. Isolates
      belonged to group VS116 (n = 10) and to B. garinii (n = 1). Our study has shown
      that Turdus sp. are infected by B. garinii and by Borrelia from group VS116 and
      that blackbirds are implicated as reservoirs for these 2 genomic groups of
      Borrelia, as they transmit living borreliae to ticks. An association seems to
      exist between birds and Borrelia VS116, and to a lesser extent, B. garinii,
      similar to the association existing between small rodents and B. afzelii. Our
      observations emphasize the fact that different enzootic cycles maintain Lyme
      borreliosis spirochetes in nature.

PMID- 9638882
TI  - Use of silica as a carrier to recover and prepare waterborne enteric viruses for
      detection by RT-PCR.
AB  - A rapid, efficient and inexpensive method was developed to concentrate poliovirus
      type 1 (PV1), rotavirus (RV) and hepatitis A virus (HAV) from artificially spiked
      samples of tap and surface water. The method consists of adsorbing the viruses to
      silicon dioxide (SiO2) in the presence of 0.5 mM AlCl3 and adjustment of the pH
      to 3.5. The silica-adsorbed virus was collected by low speed centrifugation.
      Viral RNA was then extracted with guanidium thiocyanate (GT), and environmental
      nucleases and inhibitors of reverse transcriptase and Taq polymerase were further
      eliminated from concentrates by sequential treatment with GT, ethanol and
      acetone. Subsequent RT-PCR allowed the detection of as few as 1 to 10 TCID50 of
      PV1, RV, and HAV in seeded 1 liter samples of tap water. The same protocol was
      then used with effluents from two local sewage treatment plants. These samples,
      found to be free of HAV, were most commonly contaminated with enteroviruses and
      rotaviruses. Addition of 1000 TCID50 of HAV, PV1 or RV to a second 1 liter
      sample, taken at the same time from the corresponding surface waters allowed
      detection of the input virus without discernible inhibition by amplification
      inhibitors. The newly established method seems amenable to scaling up and
      promising for virus monitoring in different water types. The method is rapid and
      results can be obtained within 24 to 36 hours.

PMID- 9638883
TI  - [Potassium as an indicator of anthropogenic contamination of swimming pool
      water].
AB  - Swimming pool water is processed, filtered and disinfected repeatedly in order to
      maintain hygienic conditions. Additionally, fresh water is added. However, it
      cannot be avoided, that the concentrations of certain components of swimming pool
      water will increase in the course of time. DIN 19,643 regulates that fresh water
      supply can be measured by nitrate concentration. Nitrate is mainly formed by
      oxidation of nitrogen containing organic compounds. Oxidation reactions are
      complex and the amount of nitrate formed by this process depends on specific
      factors which may vary in swimming pools with different technical equipment.
      Therefore nitrate is only of limited reliability to estimate fresh water addition
      in public swimming pools. Main sources for nitrogen containing compounds in pool
      water are sweat and urine which contain inorganic compounds like potassium.
      Potassium is a direct indicator of contamination. Its concentration is not
      influenced by chemical reactions because it is an inert compound. The urine
      release into the water of indoor pools was estimated by this parameter to be 77.5
      ml/person, in outdoor pools about 60 ml. Potassium concentration in swimming
      pools will reach an equilibrium concentration, depending on the size of the pool,
      the number of bathers and the amount of fresh water added. This equilibrium
      concentration is mathematically calculated in a general approach. In none of 36
      swimming pools where potassium concentration was measured, this calculated value
      was exceeded. The results indicate that the potassium concentration is a new
      valuable parameter to assess the quality of swimming pool water under hygienic
      aspects.

PMID- 9638884
TI  - [Haloforms in hot spring pools].
AB  - Chloroforme is formed during disinfection of swimming pool water in certain
      amounts depending on several cofactors. Because of its carcinogenic properties
      this compound has been frequently a subject of public discussion over the last
      couple of years. Little is known about chloroforme concentrations in spas. Spas
      are operated at significantly higher temperatures as compared to other pools, and
      the organic contamination may be higher. Therefore, chloroforme is possibly
      produced in higher amounts than in regular swimming pools. On the other hand the
      air that is blown through the bassin may reduce the concentration of this low
      volatile substance. In order to investigate the average concentration, 21 water
      samples from spas in public indoor pools were analyzed as to their chloroforme
      contend. The median of concentration was 3.8 micrograms/l. The maximum measured
      chloroforme concentration was 6.4 micrograms/l. The average chloroforme
      concentration in the filtered water was slightly higher than before filtration.
      The use of spas does not implicate an increase in chloroforme uptake by bathers.

PMID- 9638885
TI  - Factors affecting the bacteriological contamination of commercial washing
      machines.
AB  - Wash water from self-service washing machines in three commercial launderettes of
      Bologna (Italy) were examined to verify which factors affect their bacterial
      contamination and to determine which procedures in the laundering process have
      the most significant effects on the removal of bacteria. Four washing formulas
      were compared: a delicates cycle (programmed temperature 25-30 degrees C; actual
      temperature: 28-31 degrees C); a whites cycle (programmed temperature: 80-90
      degrees C; actual temperature: 50-57.5 degrees C); a delicates cycle with the
      addition of an oxygen-based bleach safe for delicate fabrics and a whites cycle
      with the addition of an oxygen-based bleach. Bacterial contamination of washing
      machines was higher in the launderette most heavely used, and, furthermore, it
      was in relation with the washing temperature and the use of bleaches. The low
      temperature laundering cycle (20-30 degrees C) did not guarantee elimination of
      bacterial content from either the inside of the washing machine or from the
      fabric being washed. Washing with water at a higher temperature, of about 55
      degrees C, or adding an oxygen-based bleach to the low temperature cycle did
      ensure a significant reduction in bacterial recovery from water samples and
      fabrics, but did not prevent bacteria such as P. aeruginosa from surviving inside
      the washing machine. Only the addition of bleaches to the hot water program
      ensured the almost total elimination of bacteria and also guaranteed their
      elimination from protected parts of the drum.

PMID- 9638886
TI  - [Johann Sigismund Elsholtz--the forgotten pioneer and German-speaking hygiene].
AB  - In 1682, the term "hygiene" appeared for the first time in the German language,
      in Johann Sigismund Elsholtz's Diaeteticon. In the author's meaning this term is
      used to describe the tenet of the maintenance of good health. In his book,
      Elsholtz who was physician at the court of Frederick William, the Great Elector
      of Brandenburg, makes suggestions for wholesome food and drinking. He demands the
      availability of clean water and of a good air and draws attention to the
      importance of personal hygiene. Thus, Elsholtz should be referred to as a German
      pioneer of hygiene whose recognition has been long overdue.

PMID- 9638887
TI  - [A Salmonella epidemic by Salmonella subspecies II 4,12,12,27:b:- at the
      University Hospital of Tubingen in April 1996].
AB  - In April 1996 four patients at the University Hospital of Tubingen became ill
      with diarrhoea at short intervals; one of the patients also suffered from fever.
      From stool samples of all four patients Salmonella subspecies II 4,12,27:b:- was
      isolated; from the patient who had fever the pathogen was also isolated from one
      blood culture. The patients were treated at different wards of the hospital. All
      four patients suffered from underlying diseases. In the course of a
      microbiological examination of the central kitchen staff of the hospital
      Salmonella subspecies II 4,12,27:b:- was isolated from a stool sample of one of
      the employees. No contact to cold blooded animals, no travel abroad and no
      symptoms of gastroenteritis were reported by the employee. When the employee had
      been temporarily suspended no further Salmonella infections occurred.

PMID- 9638888
TI  - Characterization and quantitation of parasite species in the effluents of the
      Berisso main sewage channel, Buenos Aires, Argentina.
AB  - Outbreaks of disease can be caused by pathogenic intestinal parasites in drinking
      water. La Plata, the capital of the province of Buenos Aires, Argentina, is
      located on the La Plata River; a principal tributary receiving the raw sewage
      from the city's 500,000 inhabitants via the Berisso main septic channel at an
      estimated volume of 108,390 m3/day (4516.3m3/h). To determine the parasite
      contamination level of the La Plata River, we obtained 18 sewage effluents from
      the Berisso main septic channel at its point of discharge into the river and
      concentrated these samples by filtration. This approach detected the following
      parasites at the indicated average levels (cysts/m3): members of the flagellate
      genus Giardia, more than 9000; representatives of the amoebic species Entamoeba
      histolytica, slightly more than 800 and Entamoeba coli, 5000; other amoebic
      forms, up to 23,000. These data clearly illustrate the degree of contamination
      within the La Plata River caused by the Berisso septic channel. Pollution of the
      La Plata River to this extent thus presents a high health risk for people who
      drink the water from this river even after conventional processing as well as for
      those who use the water from this portion of the river for recreation.

PMID- 9638890
TI  - Fibromyalgia is not a muscle disorder.
AB  - Originally described as "fibrositis," fibromyalgia has long been considered a
      muscle disorder, and many studies have investigated the possible pathologic basis
      of the disorder by examining muscle tissue, using various methodologic
      approaches. Although initial studies suggested a possible pathologic basis in
      muscle, most had serious methodologic limitations. More recent studies, however,
      have avoided methodologic pitfalls and indicate that the muscles of patients with
      fibromyalgia are normal. When data from studies of tenderness are also taken into
      account, the weight of evidence suggests that fibromyalgia is a chronic pain
      syndrome which has a central rather than peripheral or muscular basis.

PMID- 9638891
TI  - Skeletal muscle abnormalities in patients with fibromyalgia.
AB  - Widespread muscle pain and tender points are the most common complaints of
      fibromyalgia patients, and the underlying mechanisms responsible for these
      symptoms have been studied intensively during the past decade. It has been
      suggested that fatigue and pain may lead to decreased levels of physical activity
      in many patients. The resulting deconditioned state may itself contribute to
      muscle abnormalities. Associated symptoms such as disturbed sleep, anxiety,
      depression, or irritable bowel also may have a negative impact on muscle function
      and level of daily activities. The important interactions between the central
      nervous and musculoskeletal systems may involve another element, the
      neuroendocrine stress-response system. This review will consider both the current
      state of knowledge and also future studies which might be designed to answer more
      effectively the outstanding questions regarding the underlying pathogenesis of
      fibromyalgia.

PMID- 9638892
TI  - Neuroendocrine abnormalities in fibromyalgia and related disorders.
AB  - Fibromyalgia (FM) and related syndromes are poorly understood disorders that
      share symptoms such as pain, fatigue, sleep disturbances, and psychological
      distress. These syndromes are more common in women, and they are associated with
      psychological or physical stressors. The neuroendocrine axes are essential
      physiologic systems that allow for communication between the brain and the body.
      Interconnections among the neuroendocrine axes lead to coordinate regulation of
      these systems in both a positive and negative fashion. Several neuroendocrine
      axes have been shown to be dysfunctional in patients with FM. Although we do not
      yet understand the relationship between the reported disturbances of
      neuroendocrine function and the development or maintenance of FM and related
      syndromes, the authors have proposed that these abnormalities are important in
      symptomatic manifestations. This article reviews data showing disturbances of the
      neuroendocrine axes in FM and proposes a hypothesis of the development and
      maintenance of FM related to neuroendocrine disturbances.

PMID- 9638893
TI  - Sleep in fibromyalgia patients: subjective and objective findings.
AB  - Fibromyalgia (FM) patients report early morning awakenings, awakening feeling
      tired or unrefreshed, insomnia, as well as mood and cognitive disturbances; they
      may also experience primary sleep disorders including sleep apnea. Longitudinal
      studies have demonstrated the chronic nature of these disturbances in patients
      with FM. A distinct relationship exists between poor sleep quality and pain
      intensity. Polysomnographic findings during sleep in these patients include an
      alpha frequency rhythm, termed alpha-delta sleep anomaly, which is also seen in
      normal controls during stage 4 sleep deprivation; deep pain induced during sleep
      in normal controls also causes this anomaly. Sleep architecture is altered in FM
      patients showing an increase in stage 1, a reduction in delta sleep, and an
      increased number of arousals. Before prescribing pharmacologic compounds aimed at
      modifying sleep, adequate pain control and sleep habits should be achieved;
      tricyclic antidepressants, trazadone, zopiclone, and selective serotonin reuptake
      inhibitors, however, may be required. More research is needed to elucidate the
      cellular and molecular mechanisms involved in the sleep disturbances occurring in
      patients with FM.

PMID- 9638894
TI  - Advances in fibromyalgia: possible role for central neurochemicals.
AB  - The neurophysiologic term allodynia has been applied to fibromyalgia because
      people with that disorder experience pain from pressure stimuli which are not
      normally painful. The nociceptive neurotransmitters of animal studies are now
      relevant to this human model of chronic, widespread pain. Evidence is presented
      to implicate several chemical pain mediators (including serotonin, substance P,
      nerve growth factor, and dynorphin A) in the pathogenesis of fibromyalgia. This
      perception is hopeful because it offers many new options for the development of
      innovative therapy.

PMID- 9638895
TI  - Abnormal functional activity of the central nervous system in fibromyalgia
      syndrome.
AB  - The evaluation of pain is one of the major problems facing general practitioners
      and specialists in medicine. Although the source of pain can be usually be traced
      to specific abnormalities in a given organ system, some patients present with
      generalized pain syndromes, such as fibromyalgia, for which no specific source
      can be found. Some researchers have begun to consider that although there may be
      a somatic source of such pain at its initiation, over time the pain may be
      maintained or exacerbated by functional alterations in critical regions of the
      brain and spinal cord that are involved in pain processing or pain inhibition.
      This article describes the techniques currently used to measure regional cerebral
      blood flow (rCBF) in the brain by single photon emission computed tomography
      (SPECT) imaging, and reviews the SPECT and positron emission tomography
      literature concerning alterations in functional brain activity associated with
      pain in healthy individuals and in patients with chronic pain, including those
      with fibromyalgia. The article concludes by describing the implications of
      current knowledge about pain and abnormal functional brain activity in the
      understanding of the pathophysiology of fibromyalgia and in the development of
      therapeutic strategies to manage patients with this disorder.

PMID- 9638896
TI  - Advances in the treatment of fibromyalgia: current status and future directions.
AB  - Despite significant efforts devoted to understanding the etiopathogenesis of
      fibromyalgia, its treatment still presents a challenge to practicing clinicians,
      who must recognize the disorder and quantify the different symptoms in order to
      treat it. This article discusses recent research to identify sensitive and
      reliable measures for determining response to treatment among patients with FM,
      and the elements of therapeutic programs (pharmacologic and nonpharmacologic) for
      patients with FM along with the empirical or theoretical basis for their use.
      Future directions, including the need for systematic, controlled outcome studies
      of therapies and evaluation of variables which may mediate the effects of
      treatment, as well as demonstration that the effects produced in outcome studies
      generalize to settings beyond those in which the studies are initially conducted,
      are also discussed.

PMID- 9638897
TI  - Current concepts in the pathophysiology of abnormal pain perception in
      fibromyalgia.
AB  - Fibromyalgia is a noninflammatory rheumatic disorder characterized by chronic
      widespread musculoskeletal pain. Although many studies have described the pain
      and other clinical symptoms associated with this disorder, the primary mechanisms
      underlying the etiology of fibromyalgia remain elusive. This article reviews
      recent data supporting the links among each of three systems--the musculoskeletal
      system, the neuroendocrine system, and the central nervous system (CNS), all of
      which appear to play major roles in fibromyalgia pathophysiology--and pain in
      fibromyalgia, and concludes by presenting a model of the pathophysiology of
      abnormal pain perception in fibromyalgia which integrates the research findings
      described.

PMID- 9638898
TI  - Effect of fiber length on glass microfiber cytotoxicity.
AB  - Fiber length has been implicated as a determinant of fiber toxicity. Fibers of
      narrowly defined length can be generated by dielectrophoretic classifiers. Since
      the quantities of fibers produced are very small, we developed a rat alveolar
      macrophage microculture system to study the toxicity of these samples. The
      objective of this study was to examine the role of fiber length on the
      cytotoxicity of Manville code 100 (JM-100) fibers. Rat alveolar macrophages were
      cultured with 0-500 microg/ml of 5 lengths of JM-100 fibers on 96-well plates.
      After 18 h, well supernatants were removed and lactate dehydrogenase (LDH)
      activity was measured to assess cell damage. Chemiluminescence (CL), an
      assessment of macrophage function, was measured by adding lucigenin with or
      without zymosan, a particulate stimulus, to appropriate wells. For each fiber
      length the effects were concentration dependent: CL declined and LDH rose with
      increasing fiber concentration. Comparing the effects of different lengths showed
      the greatest toxicity from a relatively long fiber sample (mean length = 17
      microm). Microscopic examination of the interaction of fibers with macrophages
      revealed multiple macrophages attached along the length of the long fibers. This
      suggests that frustrated, or incomplete, phagocytosis may be a factor in the
      increased toxicity of longer fibers. Overall the results demonstrate that length
      is an important determinant of toxicity for JM-100 fibers.

PMID- 9638899
TI  - Ventilatory responses in awake guinea pigs exposed to acid aerosols.
AB  - This study reports experiments designed to evaluate the dose and temporal effects
      of an atmospheric pollutant, sulfuric acid (H2SO4) aerosol, on the dynamic
      components of the respiratory cycle. Ventilation was measured in a whole-body
      barometric plethysmograph in unanesthetized, unrestrained animals following a 4-h
      exposure to H2SO4 aerosol at 14.1, 20.1, or 43.3 mg/m3. Lung injury was assessed
      by histopathology and bronchoalveolar lavage (BAL). Aerosol exposure with H2SO4
      caused marked alterations in both the magnitude and composition of the
      ventilatory response, which were both dose and time dependent. At the highest
      concentration tested, there was a significant increase in tidal volume (deltaVt)
      and a decrease in breathing frequency (f) immediately after exposure. Analysis of
      BAL fluid at this time showed increased inflammatory cells and protein in the
      acid exposed animals, and histology showed hyaline membranes and acute
      inflammatory cells in the proximal acinar region. By 24 h postexposure, f
      significantly increased whereas deltaVt decreased. This pattern of breathing was
      interspersed with short periods of apnea. The onset of rapid, shallow breathing
      was associated with histological evidence of diffuse pulmonary edema. By
      contrast, the immediate postexposure period at the lowest concentration of H2SO4
      aerosol was characterized by a significant increase in f and little or no effect
      on deltaVt. These effects diminished with time, and at 24 h postexposure
      ventilatory parameters were indistinguishable from baseline values. An apparent
      crossover between the effects associated with the high and low exposure
      concentrations was seen at the intermediate exposure concentration; however,
      closer inspection of these findings on an animal-by-animal basis revealed two
      populations of animals with respiratory characteristics of either the high
      exposure or low-exposure groups. The data suggest that the guinea pig exhibits
      complex interactions between dose and time to response that are consistent with
      the activation of neural reflexes. The indirect plethysmographic method provides
      a simple means to assess these responses in a model system that avoids the use of
      anesthetics, surgery, and restraint.

PMID- 9638900
TI  - Regional brain dosimetry of trichloroethane in mice and rats following inhalation
      exposures.
AB  - While certain neuroactive volatile organic compounds (VOCs) have been reported to
      have an uneven distribution in various anatomically distinctive brain regions,
      this has not yet been reported for the short-chain aliphatic halogenated
      hydrocarbons. Therefore, the uptake and regional brain distribution of 1, 1, 1
      trichloroethane (TRI) in mice and rats following inhalation exposure were
      examined. Male Sprague-Dawley rats and CD-1 mice were exposed to TRI at either
      3500 or 5000 ppm for 10, 30, 60, or 120 min. Seven brain regions from rats and
      three from mice were sampled, and TRI concentrations in the blood and brain
      tissues were determined by headspace gas chromatography. In both species, the
      medulla oblongata was found to have the highest TRI concentrations, while cortex
      (in both species) and hippocampus (only sampled in rats) contained the lowest TRI
      concentrations. Substantial differences were also observed between the two
      species, as the mice exhibited higher capacity to accumulate TRI in the blood as
      well as in the brain regions. It appears that lipid content is a main factor
      influencing the differential disposition of TRI among the brains regions.
      Physiological differences in the respiratory systems of the two species and the
      physiochemical properties of the chemical favoring diffusion toward lipid-rich
      compartments could also have been expected to account for the patterns of
      regional distribution and species differences.

PMID- 9638901
TI  - Human in vivo and in vitro hydroquinone topical bioavailability, metabolism, and
      disposition.
AB  - Hydroquinone is a ubiquitous chemical readily available as monographed in
      cosmetic and nonprescription forms for skin lightening, and is an important
      industrial chemical. The in vivo bioavailability for 24-h application in humans
      was 45.3+/-11.2% of dose from a 2% cream formulation containing
      [14C]hydroquinone, with the majority of radioactivity excreted in the first 24 h.
      Timed skin wash and skin tape-stripping sequences showed a rapid and continuous
      movement of hydroquinone into the stratum corneum of human volunteers. Plasma
      levels taken both ipsilateral and contralateral to the topical dosing site
      contained radioactivity at the first 0.5-h sampling time. Peak plasma
      radioactivity was at 4 h in the 8-h blood sampling period. In vitro percutaneous
      absorption with fresh viable human skin gave a bioavailability of 43.3% of dose,
      and flux was calculated at 2.85 microg/cm2/h. In vitro, some of the skin samples
      were pretreated with the metabolic inhibitor sodium azide, which had no effect on
      percutaneous absorption. Receptor fluid accumulations and 24-h skin samples were
      extracted and the extracts subjected to thin-layer chromatography (TLC). Control
      [14C]hydroquinone extraction and TLC had one radioactivity peak, hydroquinone.
      Receptor fluid and skin extraction had a second peak with the same Rf as
      benzoquinone, which was decreased with azide treatment. No other peaks were
      found. Ethyl acetate extraction of urine from the in vivo study showed all
      radioactivity to be only water-soluble, free hydroquinone released following
      glucuronidase treatment. Risk assessment should not only involve the
      bioavailability of intact topical hydroquinone, but also consider phase I and
      phase II metabolism in both humans and any animal for which toxicity potential
      was assessed.

PMID- 9638902
TI  - Chlorpropham [isopropyl N-(3-chlorophenyl) carbamate] disrupts microtubule
      organization, cell division, and early development of sea urchin embryos.
AB  - The herbicide CIPC [N-(3-chlorophenyl) carbamate] has been shown to disrupt
      microtubule organization in plants, apparently by interfering with the
      functioning of the microtubule organizing center. Very few studies have examined
      the effects of CIPC on animal cell microtubules and centrosomes, however, and the
      effects of this cytoskeletal disrupting agent on fertilization and early
      development have not been studied in detail. To address these questions,
      fertilized sea urchin eggs were cultured in the presence of CIPC until the prism
      stage, and perturbations in the cytoskeleton and development were examined. It
      was found that Lytechinus pictus embryos are sensitive to micromolar amounts of
      CIPC, and that a characteristic set of cytoskeletal and developmental deficits is
      produced as a result of exposure to this herbicide. Mitotic spindles were
      truncated and randomly oriented within zygotes and blastomeres, and cytokinesis
      was compromised, resulting in the production of blastomeres of various sizes and
      ploidy. Interestingly, in spite of these cytoskeletal and nuclear alterations,
      spindle poles at fourth cleavage retained their ability to interact with the
      plasma membrane in a manner similar to that normally characterizing the unequal
      division of macromeres and micromeres. CIPC treatment resulted in unequal cell
      divisions at atypical times, and skeletal spicule formation in these embryos was
      abnormal. These results indicate that CIPC may pose a significant health risk
      during mammalian embryogenesis; in addition, it may be a useful tool with which
      to study microtubule and centrosomal functioning during animal cell division
      especially in those cell types that exhibit stereotypic patterns of cell division
      during early development.

PMID- 9638903
TI  - Evaluation of abnormal liver function in pregnancy.
AB  - Liver disease in pregnancy may present in a subtle or dramatic fashion. An
      approach using the pattern of liver function abnormalities, time of gestation,
      and constellation of symptoms will narrow the diagnostic possibilities.
      Diagnostic tests, including serology, ultrasonography of the hepatobiliary tree,
      and liver biopsy, can make a definitive diagnosis.

PMID- 9638904
TI  - Intrahepatic cholestasis of pregnancy.
AB  - Intrahepatic cholestasis of pregnancy (ICP) is a disease of the third trimester
      of pregnancy involving pruritus and elevated bile acid levels. Its pathogenesis
      likely involves a genetic hypersensitivity to estrogen. Once thought to be benign
      for both mother and fetus, ICP has been associated with increased rates of fetal
      morbidity and mortality and an increased risk of maternal coagulopathy. Optimal
      obstetric management includes delivery after establishment of fetal lung
      maturity. Many treatments have been proposed for the maternal medical management
      of ICP, none of which is ideal.

PMID- 9638905
TI  - Hepatitis in pregnancy.
AB  - The study of viral hepatitis was expanded over the past decade with the emergence
      of new viruses, therapies, and vaccination guidelines as well as new data on the
      risks of perinatal transmission. There are now at least six hepatitis viruses.
      Hepatitis A and E are causes of epidemic, enteric infection and do not carry a
      significant risk of chronic infection. Hepatitis B, C, D, and G are
      hematogenously spread and are significant causes of chronic hepatitis,
      hepatocellular carcinoma, and cirrhosis. The following report reviews the types
      of hepatitis as well as the consequences of infection to the mother and fetus.

PMID- 9638906
TI  - Hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome: a review
      of diagnosis and management.
AB  - Hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome is a form of
      severe preeclampsia that threatens the gravida and her fetus. In this report, the
      diagnostic criteria and maternal and fetal risks of HELLP are defined. Prompt
      recognition and treatment in tertiary centers is emphasized, because the
      prognosis can be adversely affected by delayed or less than optimal diagnosis and
      treatment. Management guidelines are offered for treating this disorder. The
      potential roles of corticosteroids, plasmapheresis, and expectant management are
      critically evaluated. Subsequent pregnancy outcome, contraception, and
      preventative strategies are considered.

PMID- 9638907
TI  - Acute fatty liver of pregnancy.
AB  - Acute fatty liver of pregnancy is a rare clinical entity unique to pregnancy that
      occurs during the third trimester. The obstetric team must be familiar with this
      disease because early diagnosis and prompt delivery have dramatically improved
      prognosis, which was often fatal for both mother and child. Clinicians must have
      a high index of suspicion for this condition when a woman has nausea or vomiting,
      abdominal pain (particularly epigastric), jaundice, polyuria-polydipsia (without
      diabetes), increased serum transaminase activity or thrombocytopenia in late
      pregnancy. The disease rarely recurs during a subsequent pregnancy. The cause is
      unknown, but some cases of acute fatty liver of pregnancy have been associated
      with a genetic deficiency of fatty acid beta-oxidation. Because of the
      possibility of this congenital deficiency, infants of affected mothers should
      undergo close follow-up from birth.

PMID- 9638908
TI  - Liver hematoma and rupture in pregnancy.
AB  - Liver hematoma and rupture is a rare but devastating complication of pregnancy.
      The majority of cases have been associated with severe preeclampsia, but unlike
      typical preeclampsia, it is a disease of older, multiparous patients. Although
      there are predictable findings on liver pathology, the underlying pathophysiology
      is poorly understood. Early recognition and prompt surgical intervention are
      crucial to reduce the high fetal and maternal mortality rate associated with this
      disease.

PMID- 9638909
TI  - Pregnancy after liver transplantation.
AB  - This article reviews the reported experience with pregnancy after liver
      transplantation and describes obstetric risks and medical issues that the
      maternal fetal medicine specialist has a reference for managing these pregnancies
      and for providing appropriate preconception counseling. Women who undergo liver
      transplantations have a higher risk of preeclampsia, worsening hypertension,
      preterm premature rupture of membranes, anemia, small for gestational age,
      preterm delivery, and cesarean section than the normal obstetric population.
      Women with preconceptional renal dysfunction appear to be at greatest risk for
      pregnancy complications. Women who conceived within 6 months of transplant had a
      high risk of rejection. Reproductive-aged recipients of liver allograft should
      receive contraception and preconception counseling. In an appropriately timed and
      planned pregnancy, women who undergo liver transplantations can have successful
      pregnancies with little risk to their allograft function.

PMID- 9638910
TI  - Cirrhosis and portal hypertension in pregnancy.
AB  - Cirrhosis and portal hypertension infrequently coincide with pregnancy but
      increase maternal and fetal morbidity and mortality when present. Chronic liver
      disease and portal hypertension are not contraindications to pregnancy but
      necessitate intensive monitoring throughout pregnancy. The complications of liver
      disease are numerous and pose additional risks. Management of complications
      arising during pregnancy is similar to management in the nonpregnant patient.
      Provision of optimal care for mother and fetus can require the skills of multiple
      specialties such as maternal fetal medicine, gastroenterology, nutrition, and
      surgery. This report provides guidelines for the management of cirrhosis and
      portal hypertension in pregnancy.

PMID- 9638911
TI  - Liver masses in pregnancy.
AB  - Liver masses in pregnancy are rare but when encountered pose a difficult clinical
      scenario with many diagnostic and management uncertainties. They can be
      classified as nonneoplastic and neoplastic and further subdivided into benign and
      malignant. Fortunately, benign hepatic adenomas, focal nodular hyperplasia, and
      hemangiomas appear to be the more common sources of liver masses identified in
      this generally young and healthy patient population, but the actual incidence of
      each type is unknown during pregnancy. In some areas of the world infectious
      causes are more prevalent. Malignant causes of hepatic masses carry a grave
      prognosis, similar to that for the nonpregnant population. The clinical
      presentation of a liver mass during pregnancy is similar in presentation to a
      nonpregnant patient, although symptoms may initially be attributed to pregnancy,
      and diagnosis is therefore delayed. Management varies depending on the etiology
      and size of the mass and on gestational age.

PMID- 9638912
TI  - Contraception in the patient with liver disease.
AB  - Selection of a method of contraception in patients with liver disease can be
      complicated. Tubal ligation should be considered in the setting of chronic liver
      disease for those patients who have completed families. Multiple reversible
      methods of contraception are currently available but may affect hepatic disease.
      Estrogen-containing contraceptive methods are contraindicated in patients with
      acute liver disease. Progestin contraceptives appear to be safe and multiple
      delivery systems are available. With rare exception, barrier methods and the
      intrauterine device may be offered as alternative methods.

PMID- 9638913
TI  - Effects of a circumferentially vented mask on breathing patterns of women as
      measured by respiratory kinematic techniques.
AB  - Since pneumotachograph masks are commonly used in studies of speech breathing,
      the purpose of this study was to measure the differences in respiratory
      volumetric and frequency measures during speech under two conditions: with and
      without a circumferentially vented pneumotachograph mask coupled to the face.
      Thus we sought to identify whether changes in breathing patterns occur with the
      use of a specific face mask, because these patterns are accepted as
      representative of normal speech breathing. Subjects were 10 normal-speaking
      women, each of whom produced a syllable train and a connected speech task, both
      at comfortable intensity levels. Respiratory measures were made using linearized
      magnetometers during speech production. The measurements included lung volume,
      rib cage volume, and abdominal volume at utterance initiation and termination,
      volume excursions during the utterance, and the number of breath groups during
      the speech task. There were no significant differences between the mask-on and
      mask-off conditions in volumetric and frequency measures. A significant task
      difference for abdominal initiation was found. It was concluded that the use of a
      circumferentially vented pneumotachograph mask does not alter the reliability of
      respiratory volume and frequency measures for studies of voice.

PMID- 9638914
TI  - Effect of extended exposure to frequency-altered feedback on stuttering during
      reading and monologue.
AB  - An ABA time series design was used to examine the effect of extended, continuous
      exposure to frequency-altered auditory feedback (FAF) during an oral reading and
      monologue task on stuttering frequency and speech rate. Twelve adults who stutter
      participated. A statistically significant decrease in number of stuttering
      events, an increase in number of syllables produced, and a decrease in percent
      stuttering was observed during the experimental segment relative to baseline
      segments for the oral reading task. In the monologue task, there were no
      statistically significant differences for the number of stuttering events, number
      of syllables produced, or percent stuttering between the experimental and
      baseline segments. Varying individual patterns of response to FAF were evident
      during the experimental segment of the reading task: a large consistent reduction
      in stuttering, an initial reduction followed by fluctuations in amount of
      stuttering, and essentially no change in stuttering frequency. Ten of 12
      participants showed no reduction in stuttering frequency during the experimental
      segment of the monologue task. These findings have ramifications both for the
      clinical utilization of FAF and for theoretical explanations of fluency
      enhancement.

PMID- 9638915
TI  - The effect of lung volume on selected phonatory and articulatory variables.
AB  - The purpose of the study was to examine the effects of manipulating lung volume
      (LV) on phonatory and articulatory kinematic behavior during sentence production
      in healthy adults. Five men and five women repeated the sentence "I sell a
      sapapple again" under five LV conditions. These included (1) speaking normally,
      (2) speaking after exhaling most of the air from the lungs, (3) speaking at end
      expiratory level (EEL), (4) speaking after a maximal inhalation, and (5) speaking
      after a maximal inhalation while attempting to maintain as normal a mode of
      speech as possible. From a multichannel recording, measures were made of LV,
      sound pressure level (SPL), fundamental frequency (F0) and semitone standard
      deviation (STSD), and upper and lower lip displacements and peak velocities. When
      compared with the reference condition, the sentence was spoken significantly more
      quickly at the lowest LV. SPL increased significantly for the high LV condition,
      as did the women's F0 and STSD. Upper lip displacements and peak velocities
      generally decreased for LVs other than the reference condition. Lower lip
      movements showed inconsistent changes as a function of LV. Adjustments to the LV
      for speech led to SPL and F0 changes consistent with a coordinated control of the
      respiratory system and the larynx. However, less consistent effects were observed
      in the articulatory kinematic measures, possibly because of a less direct
      biomechanical and neural control linkage between respiratory and articulatory
      structures.

PMID- 9638916
TI  - Nasal coarticulation in normal speakers: a re-examination of the effects of
      gender.
AB  - The purpose of this study was to re-examine the influence of gender on nasal
      coarticulation in normal speakers. Twenty adult speakers (10 men, 10 women)
      produced the vowel-nasal-vowel (VNV) sequence /ini/ within a carrier phrase using
      two stress patterns: (1) with equal stress placed on both syllables, and (2) with
      contrastive stress placed on the second syllable. A partitioned,
      circumferentially vented pneumotachograph mask and microphone were used to
      determine nasal airflow, ratios of nasal to oral-plus-nasal airflow, and sound
      pressure levels (SPLs) at the midpoints of the first and second vowels of the
      syllables. Volume ratios of nasal to oral-plus-nasal airflow that reflected the
      entire duration of the vowels were also obtained. Results indicated that all
      speakers except 1 woman exhibited nasal airflow at the midpoint of the first
      vowel when /ini/ was produced with equal stress; all speakers exhibited carryover
      nasal airflow during the second vowel. During contrastive stress, all speakers
      except 1 woman and 1 additional man exhibited anticipatory nasal airflow; all
      speakers exhibited carryover nasal airflow. Analysis of variance (ANOVA)
      procedures with repeated measures indicated significant main effects of syllable
      stress (p < 0.001) relative to nasal airflow and ratios of nasal to oral-plus
      nasal airflow. Regardless of the gender of the speakers, syllable stress resulted
      in reduced anticipatory and carryover nasal airflow during the first and second
      vowels of /ini/, respectively. The results suggest that (a) both men and women
      adhere to similar patterns of velar articulation, and (b) velopharyngeal closure
      during the vowel /i/ may be enhanced during stressed syllables. Implications
      relative to aspects of speech production and clinical practice are discussed.

PMID- 9638917
TI  - Altered auditory feedback research conditions and situations of everyday life:
      comments on Ingham, Moglia, Frank, Costello Ingham, and Cordes (1997)

PMID- 9638918
TI  - Psychometric equivalence of recorded spondaic words as test items.
AB  - In the determination of the speech-reception threshold (SRT), spondaic words are
      assumed to be homogeneous with respect to intelligibility; and the assumption of
      equal intelligibility requires that the words be comparable for all signal
      levels. Previous attempts to assess the equal intelligibility assumption using
      word thresholds as the sole criterion are not an adequate basis for specifying
      the equality of intelligibility. In the present study, the recorded spondaic
      words (Tillman recording) were analyzed in an attempt to create a more
      homogeneous set of spondaic words for future laboratory work. To achieve this
      goal, the data reported by Young, Dudley, and Gunter (1982) and data collected in
      our laboratory were fitted to a logistic function (psychometric function) from
      which a 50% point (threshold) and slope were obtained. To specify their
      acoustical parameters, the recorded spondaic words were digitized and the RMS
      level and duration of each syllable and word were calculated. None of the RMS or
      duration measures were correlated with word thresholds, so no attempt was made to
      equate level or duration. On the other hand, when the threshold of each word was
      adjusted to equal the mean threshold of the set (n = 36), the dispersion among
      word thresholds and slopes was greatly reduced. Further, we recommend that small
      sets of "equally intelligible" spondaic words not be used for clinical testing
      because set size is a strong factor in determining threshold for spondees (Meyer
      & Bilger, 1997; Punch & Howard, 1985).

PMID- 9638919
TI  - Hearing loss, control, and demographic factors influencing hearing aid use among
      older adults.
AB  - Preference for non-use of hearing aids among older adults who are candidates for
      amplification remains to be explained. Clinical studies have examined the
      contribution of consumer attitudes, behaviors, and life circumstances to this
      phenomenon. The present study extends the interests of earlier investigators in
      that it examines psychological control tendencies in combination with hearing
      loss and demographic variables among older adults who elected to accept
      (adherents) or ignore (nonadherents) advice from hearing professionals to acquire
      and use hearing aids. One hundred thirty-one individuals participated by
      completing measures of hearing, hearing handicap, psychological control,
      depression, and ego strength. Participants were asked to provide demographic
      information and personal opinions regarding hearing aid use. Adherence group and
      gender differences were noted on measures of hearing sensitivity, psychological
      control, and demographic factors. Female adherents demonstrated greater hearing
      loss and poorer word recognition ability but less hearing handicap, higher
      internal locus of control, higher ego strength, and fewer depressive tendencies
      than female nonadherents. They reported demographic advantages. Female adherents
      assumed responsibility for effective communication. Although male adherents and
      nonadherents did not differ significantly demographically, male adherents were
      more accepting of their hearing loss, took responsibility for communication
      problems, and found hearing aids less stigmatizing. Implications for clinical
      practice and future clinical investigations are identified and discussed. Results
      are expected to be of interest to clinicians, clinical investigators, and health
      care policymakers.

PMID- 9638920
TI  - Functional magnetic resonance imaging measures of blood flow patterns in the
      human auditory cortex in response to sound.
AB  - Functional Magnetic Resonance Imaging (fMRI) holds exciting potential as a
      research and clinical tool for exploring the human auditory system. This
      noninvasive technique allows the measurement of discrete changes in cerebral
      cortical blood flow in response to sensory stimuli, allowing determination of
      precise neuroanatomical locations of the underlying brain parenchymal activity.
      Application of fMRI in auditory research, however, has been limited. One problem
      is that fMRI utilizing echo-planar imaging technology (EPI) generates intense
      noise that could potentially affect the results of auditory experiments. Also,
      issues relating to the reliability of fMRI for listeners with normal hearing need
      to be resolved before this technique can be used to study listeners with hearing
      loss. This preliminary study examines the feasibility of using fMRI in auditory
      research by performing a simple set of experiments to test the reliability of
      scanning parameters that use a high resolution and high signal-to-noise ratio
      unlike that presently reported in the literature. We used consonant-vowel (CV)
      speech stimuli to investigate whether or not we could observe reproducible and
      consistent changes in cortical blood flow in listeners during a single scanning
      session, across more than one scanning session, and in more than one listener. In
      addition, we wanted to determine if there were differences between CV speech and
      nonspeech complex stimuli across listeners. Our study shows reproducibility
      within and across listeners for CV speech stimuli. Results were reproducible for
      CV speech stimuli within fMRI scanning sessions for 5 out of 9 listeners and were
      reproducible for 6 out of 8 listeners across fMRI scanning sessions. Results of
      nonspeech complex stimuli across listeners showed activity in 4 out of 9
      individuals tested.

PMID- 9638921
TI  - The effects of hearing loss and noise masking on the masking release for speech
      in temporally complex backgrounds.
AB  - Speech recognition was measured in three groups of listeners: those with
      sensorineural hearing loss of (presumably) cochlear origin (HL), those with
      normal hearing (NH), and those with normal hearing who listened in the presence
      of a spectrally shaped noise that elevated their pure-tone thresholds to match
      those of individual listeners in the HL group (NM). Performance was measured in
      four backgrounds that differed only in their temporal envelope: steady-state (SS)
      speech-shaped noise, speech-shaped noise modulated by the envelope of multi
      talker babble (MT), speech-shaped noise modulated by the envelope of single
      talker speech (ST), and speech-shaped noise modulated by a 10-Hz square wave
      (SQ). Threshold signal-to-noise ratios (SNRs) were typically best in the ST and
      especially the SQ conditions, indicating a masking release in those modulated
      backgrounds. SNRs in the SS and MT conditions were essentially identical to one
      another. The masking release was largest in the listeners in the NH group, and it
      tended to decrease as hearing loss increased. In 5 of the 11 listeners in the HL
      group, the masking release was nearly identical to that obtained in the NM group
      matched to those listeners; in the other 6 listeners, the release was smaller
      than that in the NM group. The reduced masking release was simulated best in
      those HL listeners for whom the masking release was relatively large. These
      results suggest that reduced masking release for speech in listeners with
      sensorineural hearing loss can only sometimes be accounted for entirely by
      reduced audibility.

PMID- 9638922
TI  - Selective visual masking in speechreading.
AB  - Using digital video technology, selective aspects of a face can be masked by
      identifying the pixels that represent it and then, by adjusting the gray levels,
      effectively eliminate that facial aspect. In groups of young adults with normal
      vision and hearing, consonant-viseme recognition was measured for closed sets of
      vowel-consonant-vowel disyllables. In the first experiment viseme recognition was
      measured while the tongue and teeth were masked and while the entire mouth was
      masked. The results showed that masking of the tongue and teeth had little effect
      on viseme recognition, and when the entire mouth was masked, participants
      continued to identify consonant visemes with 70% or greater accuracy in the /a/
      and /(ball)/ vowel contexts. In the second experiment, viseme recognition was
      measured when the upper part of the face and the mouth were masked and when the
      lower part of the face and the mouth were masked. The results showed that when
      the mouth and the upper part of the face were masked, performance was poor, but
      information was available to identify the consonant-viseme /f/. When the mouth
      and the lower part of the face were masked, viseme recognition was quite poor,
      but information was available to discriminate the consonant-viseme /p/ from other
      consonant visemes.

PMID- 9638923
TI  - Children's imitations of intonation contours: are rising tones more difficult
      than falling tones?
AB  - Perceptual evidence suggests that young children do not imitate adult-modeled
      intonation patterns with a rising pitch contour (rising tones) as well as those
      with a falling pitch contour (falling tones). To investigate the acoustic basis
      of this uneven imitation pattern, 10 4-year-old children were asked to imitate
      short sentences with falling and rising tones in 4 sentence contexts called
      "intonation groups." The results indicated that the children used more falling
      tones than adults in most intonation groups. When the children matched the adult
      modeled contour direction (falling or rising), the children's speed of pitch
      change was comparable to that of adults in the falling tones of final intonation
      groups and in the rising tones of nonfinal groups, but was slower than that of
      adults in the complementary environments. In a manner consistent with previously
      reported perceptual data, the instrumental findings indicate that rising tones
      may be more difficult for 4-year-old children to produce than falling tones. The
      results additionally suggest that children's intonation is sensitive not only to
      the direction of tonal contours but also to their position in sentence-final
      versus nonfinal intonation groups.

PMID- 9638924
TI  - Young children's acquisition of the movement aspect in American Sign Language:
      parental report findings.
AB  - The acquisition of the movement aspect of American Sign Language signs was
      examined longitudinally in 9 young children of deaf parents. During monthly home
      visits, the parents demonstrated on videotape how their children formed the
      different signs in their lexicons. The parents also demonstrated how they formed
      or modeled these same signs. Overall, the children correctly produced 61.4% of
      the movements that were present in the adult sign models. Although the production
      accuracy of the movement aspect of signs did not improve over the course of the
      study, the number and complexity of movements produced by the children did
      increase as they got older and their vocabularies grew in size. Of the different
      sign movements, contacting action was by far the most frequently produced. The
      children were also relatively successful in their production of closing action
      and downward movement. The order of acquisition for the remaining ASL movements,
      however, was quite variable, with the exception that bidirectional movements
      tended to be produced more accurately than unidirectional movements. The
      relationship between children's early rhythmical motor behaviors and the
      development of sign movements is discussed.

PMID- 9638925
TI  - Written language comprehension in younger and older adults.
AB  - This study examined the effects of text genre and repeated reading on written
      language comprehension in younger (M = 21 years) and older (M = 72 years) healthy
      adults (N = 54). Participants verified four text-based statements (i.e.,
      explicit, implicit, contradictory, and elaborated) after reading expository,
      narrative, and procedural texts. Verification accuracy was comparable for both
      age groups; however, text genre, statement-type, and repeated reading produced
      significant effects. Expository passages, explicit and implicit statements, and
      repeated reading yielded superior results. Procedural passages and contradictory
      and elaborated statements yielded less accurate results. Statement-types invoked
      multiple levels of cognitive representation across text genres and age groups.
      Overall, reading time was significantly faster for younger adults, and reading
      times were significantly faster for both age groups during the repeated reading
      trial. Text genre also influenced reading time, with expository passages read
      faster than narrative and procedural passages. These findings suggest the
      appreciable influences of text genre and repeated reading on measures of text
      processing and comprehension in healthy adults, irrespective of age.

PMID- 9638926
TI  - Socioeconomic status and gender influences on children's dialectal variations.
AB  - This investigation compares dialect use by African American children differing in
      socioeconomic status (SES) and gender. Subjects were 5- and 6-year-old boys (n =
      30) and girls (n = 36), who were kindergartners attending schools in the
      Metropolitan Detroit area. Comparisons of the amount of dialect in the children's
      spontaneous discourse revealed systematic differences relative to SES and gender
      in the frequencies but not the forms of dialect in use. Children from lower
      income homes, and boys, were more marked dialect users than their middle-class
      peers or girls. The sociolinguistic implications of the findings are discussed.

PMID- 9638927
TI  - Concurrent and predictive validity of an early language screening program.
AB  - The efficacy of screening 2-year-old children for language delay using a parent
      report questionnaire was investigated in three studies. The Language Development
      Survey (Rescorla, 1989) was mailed to 650 families at the time of their child's
      second birthday. Fifty-three percent of the surveys received by parents were
      completed and returned. Screening outcomes were then compared, in double-blind
      fashion, with the results of comprehensive clinical evaluations at ages 2 (N =
      64) and 3 (N = 36). Parents' report of the size of their children's expressive
      vocabularies was highly correlated with clinical language measures at age 2.
      Children who screened positive performed significantly poorer than children who
      screened negative on standardized language tests and on measures taken from
      spontaneous conversation. The screening program demonstrated excellent
      sensitivity and specificity for identifying language delay at age 2 but somewhat
      lower levels for predicting developmental status one year later.

PMID- 9638928
TI  - The acquisition of Arabic consonants.
AB  - This normative study of the acquisition of consonants of Arabic as spoken in
      Jordan answered 4 questions: (1) What percentage of children at each of 9 age
      levels produced each consonant correctly? (2) What are the ages of customary
      production, mastery, and acquisition for each phoneme? (3) Does accuracy of
      consonants within sound classes vary by position in the word? (4) What are the
      differences in ages of acquisition between Arabic and English? Samples were
      collected from 180 normally developing children between the ages of 2:0 and 6:4.
      The percentages of accuracy of both standard and acceptable consonants were
      plotted and showed clear developmental trends. Medial consonants were
      significantly more accurate than initial and final consonants. The ages of
      customary production, acquisition, and mastery of Arabic consonants were similar
      to those for English but with notable exceptions that have implications for
      description of phonological acquisition. Support for previously proposed
      universal sound acquisition sequences was found, but some language-specific
      effects were also seen.

PMID- 9638929
TI  - Short-term memory and language outcomes after extreme prematurity at birth.
AB  - The performance of 26 children (3;0-4;0 years) who were born before 32 weeks
      gestation was compared with the performance of 26 full-term children on a range
      of short-term memory and language measures. The measures tested vocabulary,
      expressive language, phonological short-term memory, and general nonverbal
      ability. Preterm children scored more poorly across the full range of measures.
      The mildly depressed performance of the preterm group on the short-term memory
      and language measures was attributable to the large deficits on these tests shown
      by a subgroup of approximately one third of preterm children identified as being
      "at risk" for persisting language difficulties using the Bus Story Test (Bishop &
      Edmundson, 1987). The findings indicate that preterm birth and associated hazards
      may constitute a significant risk factor for specific language impairment in a
      sizable minority of children.

PMID- 9638930
TI  - Communicative competence as perceived by adults with severe speech impairments
      associated with cerebral palsy.
AB  - The effects of aided message length (single-word vs. phrase-generated messages)
      and partner feedback (presence vs. absence of expanded message repetitions) on
      perceptions of the communicative competence of an adult augmentative and
      alternative communication (AAC) system user were examined. Subjects consisted of
      12 nonambulatory adults with severe speech impairments associated with cerebral
      palsy. Four scripted videotaped conversational conditions involving the AAC
      system user and a typically speaking partner were employed to manipulate the two
      independent variables. A balanced incomplete block design was used. Following
      each viewing, subjects completed a questionnaire designed to assess the
      communicative competence of the AAC system user. Results indicated that neither
      independent variable had an impact on the subjects' ratings of communicative
      competence. Findings are compared with those from an earlier investigation, and
      clinical implications are discussed.

PMID- 9638931
TI  - Acquisition of linguistic and cognitive skills by children with cleft palate.
AB  - This study compared the early cognitive and linguistic development of young
      children with cleft palate (N = 28) to that of noncleft children (N = 29).
      Measures included the Mental scale of the Bayley Scales of Infant Development,
      the Minnesota Child Development Inventory, Mean Length of Utterance, and words
      acquired by 24 months. Children with cleft palate, although well within the
      normal range, performed significantly below the children in the control group on
      the Mental Scale of the Bayley Scales of Infant Development, some subscales of
      the Minnesota Child Development Inventory, and words acquired by 24 months.
      Differences observed in the cognitive development of children with and without
      cleft palate were verbal as opposed to nonverbal (i.e., linguistic in nature) and
      were related to hearing status at 12 months and velopharyngeal adequacy.

PMID- 9638932
TI  - The socioemotional behaviors of children with SLI: Social Adaptation or Social
      Deviance?
AB  - Two models of the relationship between socioemotional behavior and verbal
      abilities are compared: Social Adaptation and Social Deviance. The socioemotional
      integrity of 17 children with specific language impairment (SLI) and 20
      unaffected children who were age-matched (AM) was examined using the Child
      Behavior Checklist (CBCL) and the Teacher's Report Form (TRF) at kindergarten and
      first grade. All CBCL and TRF syndrome scale means for both groups were within
      normal limits. Significant group x respondent interaction effects were observed;
      teachers, and not parents, rated the children with SLI as having more social and
      internalizing behavioral problems than their AM peers. Significant differences
      between groups were restricted to internalizing, social, and attention problems.
      Very little congruence or stability over time was observed in the clinical
      ratings. The outcomes support a Social Adaptation Model of socioemotional
      behavior and language impairment. Implications for the clinical management of
      children with SLI are discussed.

PMID- 9638933
TI  - Deficits in finite verb morphology: some assumptions in recent accounts of
      specific language impairment.
AB  - The grammatical morphology deficits common in children with specific language
      impairment (SLI) are characterized in some models as linguistic deficits. Such
      models must assume some mechanism for correct productions of finite verb forms.
      Three such assumptions were tested by analyzing speech samples from 18 children
      with SLI (aged 3 years 6 months to 6 years 9 months). Assumption 1, that
      nonfinite forms are used consistently until replaced by memorized finite forms,
      was tested by examining the distribution of verb types in present third-person
      singular and noun types in present third-person singular contractible copula
      contexts. Significantly more word types than expected were inflected
      inconsistently. Both Assumption 2, that finite and nonfinite verb forms are
      memorized but used indiscriminately, and Assumption 3, that affixation rules are
      applied indiscriminately, predict random use of finite forms. This prediction was
      not supported.

PMID- 9638934
TI  - High sensitivity analysis of proteins and peptides by capillary electrophoresis
      tandem mass spectrometry: recent developments in technology and applications.
AB  - Analytical biochemistry, in particular the analysis of regulatory proteins that
      control biological systems and pathways, is dependent on methods of ever
      increasing sensitivity. Capillary electrophoresis (CE) has long been recognized
      as an ultrasensitive analytical technique. In spite of the high sensitivity, CE
      has not penetrated protein discovery research as a standard analytical method. In
      this review article we summarize recent technical developments which have
      significantly enhanced CE as a tool for the analysis of trace amounts of
      proteins. Specifically, we review recent advances in the development and
      application of capillary electrophoresis-mass spectrometry (CE-MS) and on-line
      analyte concentration techniques, and introduce the emerging field of
      microfluidics as a front end to mass spectrometry (MS).

PMID- 9638935
TI  - Database searching using mass spectrometry data.
AB  - Large-scale DNA sequencing is creating a sequence infrastructure of great benefit
      to protein biochemistry. Concurrent with the application of large-scale DNA
      sequencing to whole genome analysis, mass spectrometry has attained the
      capability to rapidly, and with remarkable sensitivity, determine weights and
      amino acid sequences of peptides. Computer algorithms have been developed to use
      the two different types of data generated by mass spectrometers to search
      sequence databases. When a protein is digested with a site-specific protease, the
      molecular weights of the resulting collection of peptides, the mass map or
      fingerprint, can be determined using mass spectrometry. The molecular weights of
      the set of peptides derived from the digestion of a protein can then be used to
      identify the protein. Several different approaches have been developed. Protein
      identification using peptide mass mapping is an effective technique when studying
      organisms with completed genomes. A second method is based on the use of data
      created by tandem mass spectrometers. Tandem mass spectra contain highly specific
      information in the fragmentation pattern as well as sequence information. This
      information has been used to search databases of translated protein sequences as
      well as nucleotide databases such as expressed sequence tag (EST) sequences. The
      ability to search nucleotide databases is an advantage when analyzing data
      obtained from organisms whose genomes are not yet completed, but a large amount
      of expressed gene sequence is available (e.g., human and mouse). Furthermore, a
      strength of using tandem mass spectra to search databases is the ability to
      identify proteins present in fairly complex mixtures.

PMID- 9638936
TI  - Sample handling for proteome analysis.
AB  - The main factor limiting the sensitivity range for the identification of proteins
      isolated by two-dimensional (2-D) electrophoresis is sample handling: protein
      detection limits on the gel, losses during extraction and digestion, as well as
      interference of gel contaminants and detergents with the mass spectrometry (MS)
      detection increasing background noise. At the one hundred picomole level, losses
      are fairly negligible but when the amounts drop below 1 picomole (and
      subfemtomole peptide detection limits have been reported recently by MS), the
      losses become a critical point. In order to extend proteome analysis to include
      very low copy number proteins, methods must be developed to minimize losses and
      handling steps, maximize digestion and extraction yields, as well as to lower
      chemical noise. We present several methods that we have developed in our
      laboratory to: (i) increase the amount of material available in a sodium dodecyl
      sulfate (SDS)-free form which does not require staining, (ii) increase protein
      extraction and digestion yields and lower the contamination by autoproteolytic
      products, and (iii) allow direct modification of the peptide mixture to generate
      sequence tags.

PMID- 9638937
TI  - A peptide concentration and purification method for protein characterization in
      the subpicomole range using matrix assisted laser desorption/ionization
      postsource decay (MALDI-PSD) sequencing.
AB  - We here describe the use of added reversed-phase chromatographic beads to
      concentrate peptides from highly diluted solutions. In the procedure developed,
      peptide-bead suspensions are dried under vacuum to complete dryness; peptides are
      subsequently eluted in a small volume of matrix-assisted laser
      desorption/ionization (MALDI)-matrix containing organic/aqueous solvent and
      transferred to a MALDI-target for mass analysis. We show that by using this bead
      peptide concentration procedure, low femtomole amounts of peptides are
      efficiently concentrated, up to 1000 times, to volumes smaller than 0.7 microL.
      We have used this concentration procedure in combination with MALDI-post-source
      decay analysis to identify subpicomole amounts of proteins present in
      polyacrylamide gels. Furthermore, we show that the bead-peptide concentration
      method can be elegantly used to clean up samples contaminated with high
      concentrations of substances normally deleterious to MALDI-mass spectrometry (MS)
      experiments. We have found additionally that the bead-peptide concentration
      procedure can be successfully used to store low femtomole amounts of peptide for
      prolonged periods of time without severe losses of peptide material. This bead
      peptide concentration procedure therefore seems to be a simple and convenient
      step in the MALDI-MS sample preparation process.

PMID- 9638938
TI  - Peptide mass fingerprint sequence coverage from differently stained proteins on
      two-dimensional electrophoresis patterns by matrix assisted laser
      desorption/ionization-mass spectrometry (MALDI-MS).
AB  - Identification of proteins separated by two-dimensional electrophoresis (2-DE) is
      a necessary task to overcome the purely descriptive character of 2-DE and a
      prerequisite to the construction of 2-DE databases in proteome projects. Matrix
      assisted laser desorption/ionization-mass spectrometry (MALDI-MS) has a
      sensitivity for peptide detection in the lower fmol range, which should be
      sufficient for an analysis of even weakly silver-stained protein spots by peptide
      mass fingerprinting. Unfortunately, proteins are modified by the silver staining
      procedure, leading to low sequence coverage. Omission of glutaraldehyde increased
      the sequence coverage, but this improved sequence coverage is still clearly below
      the sequence coverage starting with Coomassie Brilliant Blue (CBB) R-250-stained
      spots. Other factors additionally seem to modify proteins during silver staining.
      By decreasing the protein amount, the advantage of very sensitive detection on
      the gel is lost during identification, because the resulting low sequence
      coverage is not sufficient for secure identification. Low-quantity proteins can
      be identified better starting with CBB G-250 or Zn-imidazol-stained proteins. In
      contrast, for high-quantity CBB R-250-stained spots, a sequence coverage of up to
      90% can be obtained by using only one cleaving enzyme, and up to 80% was reached
      for medium-quantity spots after combination of tryptic digest with Asp-N- and Glu
      C digest.

PMID- 9638939
TI  - Additional possible tools for identification of proteins on one- or two
      dimensional electrophoresis.
AB  - Additional, essentially chemical, identification methods of proteins in
      polyacrylamide gel electrophoresis are described. Two cleavages of peptide bonds
      were used at the C-side of aspartic acid with a 0.2% pentafluoropropionic acid
      (PFPA) aqueous vapor at 90 degrees C for 4-16 h, and the N-side of
      serine/threonine with an S-ethyl trifluorothioacetate vapor at 50 degrees C for 6
      24 h. The products were analyzed by mass spectrometry-peptide mass
      fingerprinting. A new type of C-terminal sequencing at multisites of protein was
      introduced. An aqueous vapor of 90% PFPA at 90 degrees C for 2-16 h provided
      cleavages at the C-side of aspartic acid and the N-side of serine/threonine and
      simultaneous successive truncation at the C-termini of the cleaved fragments. The
      product resulted in C-terminal sequences at multisites in proteins by mass
      spectrometric analysis. The following chemical deblocking methods were used.
      Anhydrous hydrazine vapor at -5 degrees C for 8 h deblocked the N-formyl group,
      and the vapor at 20 degrees C for 4 h deblocked pyrrolidone carboxylate. N
      acetylserine/threonine was deblocked by aqueous vapor of 75% PFPA at 50 degrees C
      for 1 h, followed by reaction with p-sulfophenylisothiocyanate at pH 6.0. These
      methods were applied to a variety of protein spots on polyacrylamide gels. A new
      stepwise C-terminal sequencing of protein from polyacrylamide gels is also
      described.

PMID- 9638940
TI  - Identification of gel-separated proteins by liquid chromatography-electrospray
      tandem mass spectrometry: comparison of methods and their limitations.
AB  - We have compared several different experimental systems currently in use in our
      laboratory for protein identification by high performance liquid chromatography
      electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) after sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The efficiency of
      peptide recovery from trypsin-digested gel bands or electroblotted membrane
      slices was examined using 35S-labeled yeast proteins, and was found to be in
      excess of 80%. A dilution series of two standard proteins, bovine serum albumin
      (BSA) and carbonic anhydrase (CA), was analyzed by HPLC-ESI-MS/MS to determine
      what amount of protein could be loaded onto a gel and successfully identified, a
      measure we refer to as the practical detection limit. We were able to identify
      both standards at the 500 ng level in samples prepared from gel slices, using
      either a regular spray or a flow-split microspray HPLC-MS interface system. In
      samples prepared from membrane pieces, carbonic anhydrase was also identified at
      the 500 ng level, while bovine serum albumin could only be identified in samples
      of more than 1000 ng. In general, protein identification was slightly better in
      samples prepared from gels rather than membranes. A dilution series of lesser
      amounts of the same standard proteins was also analyzed using a gradient
      capillary LC system and we were able to successfully identify 50 ng of carbonic
      anhydrase and 100 ng of BSA.

PMID- 9638941
TI  - Capillary column chromatography improves sample preparation for mass
      spectrometric analysis: complete characterization of human alpha-enolase from two
      dimensional gels following in situ proteolytic digestion.
AB  - Two-dimensional polyacrylamide gel electrophoresis (2-DE) in combination with
      mass spectrometry is an extremely powerful tool for characterizing complex
      mixtures of proteins. In many cases, the success of this approach relies upon the
      ability to recover peptides at high concentrations and free of interfering
      artifacts from in-gel and/or on-membrane enzymatic digests. In previous studies,
      we demonstrated that capillary or microcolumn (< 350 microm ID) reversed-phase
      high performance liquid chromatography (RP-HPLC) is a powerful microseparation
      technique for proteins and peptides (Moritz, R. L. and Simpson, R. J., J.
      Chromatogr. 1992, 599, 119-130). Here we evaluate various capillary column RP
      HPLC/mass spectrometric approaches for identifying and characterizing 2-DE
      resolved proteins. For these studies, stable and efficient 0.20 mm and 0.32 mm
      internal diameter (ID) fused-silica columns with hydrophilic polyvinylidene
      difluoride (PVDF) frits were fabricated and slurry packed with 7 microm
      spherical, 300 A pore size, C8 bonded phase silica particles. We show that
      capillary column chromatography is a rapid and efficient desalting/concentrating
      (ON/OFF) technique for sample cleanup prior to protein identification by peptide
      mass fingerprinting using matrix-assisted laser desorption ionization (MALDI)
      time-of-flight mass spectrometry. While marginally more peptide mass information
      can be obtained by stepped elution of the peptide mixture with increasing
      concentrations of organic solvent, best results were obtained by fractionation of
      the peptide mixture using a linear 60 min gradient. One salient feature of this
      study was the observation that, in contrast to the stepped elution and gradient
      approaches, the ionization of peptide T1 (m/z 2402.2 SGETEDTFIADLVV(PeCys)TGQIK)
      was almost completely suppressed using the ON/OFF approach. Maximal amino acid
      sequence coverage, a necessary prerequisite for complete characterization of a
      protein, was accomplished using a capillary column (0.2 mm ID) directly coupled
      with an electrospray ionization (ESI) ion-trap tandem mass spectrometer. For
      example, from an in situ tryptic digest of alpha-enolase isolated by 2-DE from
      the human breast carcinoma cell line MDA-MB231, 71% of the amino acid sequence
      was obtained. In addition to identifying two possible N-terminal acetylated alpha
      enolase variants, Asn153Asp and Ile152Asp/Asn153Ile, the tandem mass
      spectrometric data revealed the presence of a number of process-induced
      modifications of alpha-enolase such as methionine oxidation and cysteine
      amidoethylation.

PMID- 9638942
TI  - Optimization of capillary chromatography ion trap-mass spectrometry for
      identification of gel-separated proteins.
AB  - The current paradigm for protein identification using mass spectrometric derived
      peptide-mass and fragment-ion data employs computer algorithms which match
      uninterpreted or partially interpreted fragment-ion data to sequence databases,
      both protein and translated nucleotide sequence databases. Nucleotide sequence
      databases continue to grow at a rapid rate for some species, providing an
      unsurpassed resource for protein identification in those species. Ion-trap mass
      spectrometers with their ability to rapidly generate fragment-ion spectra in a
      data-dependent manner with high sensitivity and accuracy has led to their
      increased use for protein identification. We have investigated various parameters
      on a commercial ion trap-mass spectrometer to enhance our ability to identify
      peptides separated by capillary reversed phase-high performance liquid
      chromatography (RP-HPLC) coupled on-line to the mass spectrometer. By
      systematically evaluating the standard parameters (ion injection time and number
      of microscans) together with selection of multiple ions from the full mass range,
      improved tandem mass spectrometry (MS/MS) spectra were generated, facilitating
      identification of proteins at a low pmol level. Application of this technology to
      the identification of a standard protein and an unknown from an affinity-enriched
      mixture are shown.

PMID- 9638943
TI  - Rapid identification of comigrating gel-isolated proteins by ion trap-mass
      spectrometry.
AB  - In the search for novel nuclear binding proteins, two bands from a sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gel were analyzed and each
      was found to contain a number of proteins that subsequently were identified by
      tandem mass spectrometry (MS/MS) on a quadrupole ion trap instrument. The bands
      were digested with trypsin in situ on a polyvinylidene difluoride (PVDF) membrane
      following electroblot transfer. Analysis of a 2.5% aliquot of each peptide
      mixture by matrix assisted laser desorption/ionization-mass spectrometry (MALDI
      MS) followed by an initial database search with the peptide masses failed to
      identify the proteins. The peptides were separated by reversed-phase capillary
      high performance liquid chromatography (HPLC) in anticipation of subsequent Edman
      degradation, but mass analysis of the chromatographic fractions by MALDI-MS
      revealed multiple, coeluting peptides that precluded this approach. Selected
      fractions were analyzed by capillary HPLC-electrospray ionization-ion trap mass
      spectrometry. Tandem mass spectrometry provided significant fragmentation from
      which full or partial sequence was deduced for a number of peptides. Two stages
      of fragmentation (MS3) were used in one case to determine additional sequence.
      Database searches, each using a single peptide mass plus partial sequence,
      identified four proteins from a single electrophoretic band at 45 kDa, and four
      proteins from a second band at 60 kDa. Many of these proteins were derived from
      human keratin. The protein identifications were corroborated by the presence of
      multiple matching peptide masses in the MALDI-MS spectra. In addition, a novel
      sequence, not found in protein or DNA databases, was determined by interpretation
      of the MS/MS data. These results demonstrate the power of the quadrupole ion trap
      for the identification of multiple proteins in a mixture, and for de novo
      determination of peptide sequence. Reanalysis of the fragmentation data with a
      modified database searching algorithm showed that the same sets of proteins were
      identified from a limited number of fragment ion masses, in the absence of mass
      spectral interpretation or amino acid sequence. The implications for protein
      identification solely from fragment ion masses are discussed, including
      advantages for low signal levels, for a reduction of the necessary interpretation
      expertise, and for increased speed.

PMID- 9638944
TI  - Analyzing glycoproteins separated by two-dimensional gel electrophoresis.
AB  - Two-dimensional (2-D) electrophoresis is the preferred method for separating the
      glycoforms of proteins. The isoforms usually present as 'trains' of spots in the
      first dimension and may also differ in molecular weight. The primary goal for
      analyzing the carbohydrate content of glycoprotein spots is to understand the
      'rules' which govern the migration of glycoproteins in 2-D electrophoresis. These
      rules can then be used to produce predictive vectors to interpret changes in
      glycosylation patterns. Techniques for the analysis of oligosaccharides released
      from glycoproteins which have been electroblotted to PVDF membrane after one
      dimensional (1-D) and 2-D preparative gel electrophoresis are described. The
      oligosaccharides are removed enzymatically (PNGase F of N-linked
      oligosaccharides) or chemically (beta-elimination of O-linked oligosaccharides)
      and separated by high performance anion exchange chromatography (HPAEC-PAD) and
      identified by electrospray ionization mass spectrometry (ESI-MS) or analyzed
      directly by ESI-MS. After enzymic removal of the N-linked oligosaccharides the
      protein spots can be further analyzed by Edman sequence tagging for
      identification and quantitation of the protein and by acid hydrolysis for
      monosaccharide analysis of the O-linked oligosaccharides. These approaches have
      been proved on 1-D PAGE electroblotted bovine fetuin and human glycophorin A and
      then used to analyze two abundant proteins which separate as glycoforms on 2-D
      PAGE preparative narrow range (pH 4.5-5.5) blots of human plasma: alpha2-HS
      glycoprotein (human fetuin) and alpha1-antitrypsin (alpha1-protease inhibitor).
      It is apparent that both the macroheterogeneity (site occupation) and
      microheterogeneity (diversity of structures) of the glycosylation contribute to
      the separation of protein isoforms in 2-D PAGE.

PMID- 9638945
TI  - The identification of peptide modifications derived from gel-separated proteins
      using electrospray triple quadrupole and ion trap analyses.
AB  - Microspray tandem mass spectrometry (MS/MS) in combination with database search
      routines has become a powerful tool for the identification of proteins from
      femtomole amounts of material following gel electrophoresis and in-gel digestion
      procedures. However, artifactual modification of susceptible residues can arise
      during gel electrophoresis, leading to unexpected peptide mass shifts during mass
      analysis. Consequently, collision-induced dissociation (CID) spectra generated
      from these derivatized peptides can defy direct interpretation by automated
      database search routines and remain unidentified. Here, we evaluate the MS/MS
      spectra of peptides carrying oxidized derivatives of tryptophane and methionine
      residues, and various modifications of cysteine. We demonstrate that certain of
      these modifications generate characteristic fragmentation patterns or
      "fingerprints", during CID analysis, the knowledge of which can facilitate the
      interpretation of the spectra. We will show that these signature fragment ions
      are predominantly produced during the CID analysis of singly charged ions
      although they can be observed in the MS/MS spectra of the doubly charged species
      as well. In other cases, the CID spectrum lacks a characteristic fingerprint and
      the modification remains silent. However, CID spectra of related peptides,
      differing only by their modifications, are similar and all or part of the
      fragment ion spectra will have shifted by a discreet mass, which facilitates the
      identification of the modified residue. At the same time, the comparison of
      related spectra can prevent misinterpretations such as the assignment of a
      residue mass to the wrong amino acid or a neutral loss fragment ion to a gamma-
      or b-ion.

PMID- 9638946
TI  - Protein identification using mass spectrometric information.
AB  - In an effort to gain an understanding of the value of the information in
      different mass spectrometric measurements for protein identification, the genome
      of Saccharomyces cerevisiae was studied in silico. We calculate how constraining
      the knowledge of the mass of a proteolytic peptide is as a function of mass and
      mass accuracy. We also assess the value for protein identification of additional
      information concerning a proteolytic peptide, including the presence or absence
      of a given amino acid, the number of exchangeable hydrogens, the N-terminal
      sequence, and the masses of mass spectrometrically produced fragment ions.
      Knowledge of the relative value of these different constraints is useful in the
      design of efficient protein identification experiments. Finally, we describe a
      software tool, PepFrag, for searching protein and DNA sequence databases that can
      use different types of mass spectrometric information to restrict the search.

PMID- 9638947
TI  - Two-dimensional electrophoresis of human placental mitochondria and protein
      identification by mass spectrometry: toward a human mitochondrial proteome.
AB  - Owing to the complexity of higher eukaryotic cells, characterization of a
      complete proteome is likely to be difficult to achieve. However, advantage can be
      taken of the cell compartmentalization to build organelle proteomes, which can
      moreover be viewed as specialized tools to study specifically the biology and
      "physiology" of the target organelle. Within this frame, we report here the
      construction of the human mitochondrial proteome, using placenta as the source
      tissue. Protein identification was carried out mainly by peptide mass
      fingerprinting, but other methods were also used (N-terminal microsequencing,
      blotting). The optimization steps in two-dimensional (2-D) electrophoresis needed
      for proteome research are discussed. However, the relative paucity of data
      concerning mitochondrial proteins is still the major limiting factor in building
      the corresponding proteome, which should be a useful tool for researchers working
      on human mitochondria and their deficiencies.

PMID- 9638948
TI  - Identification of phosphorylated proteins from thrombin-activated human platelets
      isolated by two-dimensional gel electrophoresis by electrospray ionization-tandem
      mass spectrometry (ESI-MS/MS) and liquid chromatography-electrospray ionization
      mass spectrometry (LC-ESI-MS).
AB  - Two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) is a powerful tool
      to separate complex protein mixtures including whole cell lysates. In combination
      with immunoblotting techniques or radioactive labeling techniques it is a fast
      and convenient way to demonstrate the presence of certain proteins or protein
      modifications. With the development of extremely sensitive analytical techniques
      such as matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS)
      or electrospray ionization (ESI)-MS, it has become possible to use 2-D gels not
      only as an analytical but also as a preparative tool. Starting with a number of
      spots excised from 2-D gels, a protein can be identified using different
      strategies involving enzymatic cleavage of the protein in the gel matrix, elution
      of the resulting peptides and analysis of these peptides by mass spectrometry.
      The obtained peptide mass fingerprint or fragment ion spectra from peptides can
      be used to screen protein or nucleic acid databases in order to identify the
      protein. We have used the techniques described above to identify proteins from
      human platelets which change their phosphorylation state following activation of
      platelets by thrombin. Platelets were radioactively labeled with
      [32P]orthophosphate and stimulated. Several protein spots in the observed range
      of 10-80 kDa and an isoelectric point of 3-10 showed a significant increase or
      decrease in phosphorylation. We present the results from the investigation of a
      spot group representing different isoforms and phosphorylation states of myosin
      light chain.

PMID- 9638949
TI  - Correlation of acidic and basic carrier ampholyte and immobilized pH gradient two
      dimensional gel electrophoresis patterns based on mass spectrometric protein
      identification.
AB  - Separation of proteins on either carrier ampholyte-based or immobilized pH
      gradient-based two-dimensional (2-D) gels gives rise to electrophoretic patterns
      that are difficult to compare visually. In this paper we have used matrix
      assisted laser desorption/ionization mass spectrometry (MALDI-MS) to determine
      the identities of 335 protein spots in these two 2-D gel systems, including a
      substantial number of basic proteins which had never been identified before.
      Proteins that were identified in both gel systems allowed us to cross-reference
      the gel patterns. Vector analysis of these cross-references demonstrated that
      there is no obvious pattern by which the mobility of a protein in one gel system
      can be used to predict its mobility in the other. Thus, as laboratories adopt the
      immobilized pH gradient-based 2-D gel systems, the only reliable means of
      translating the data gained with the carrier ampholyte-based gel system is to
      positively identify the proteins in both 2-D systems.

PMID- 9638950
TI  - Routine identification of proteins from sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) gels or polyvinyl difluoride membranes using matrix
      assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF
      MS).
AB  - As the resource laboratory for Rockefeller University our emphasis continues to
      be on methodology development for the routine analysis of low abundance proteins
      isolated from native sources. In the past ten years, gel electrophoresis of
      proteins has become the method of choice for the preparation of microgram and
      submicrogram quantities of protein for primary structural characterization, and
      over 95% of the samples submitted for protein identification are either in a gel
      or bound to polyvinyl difluoride membranes (PVDF). As such, we employ multiple
      microanalytical approaches encompassing Edman sequence degradation, amino acid
      and matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) mass
      spectrometric analysis to provide an integrated protein characterization of such
      samples. Here we describe the two major services we employ when providing protein
      identification from in-gel or PVDF-bound proteins.

PMID- 9638951
TI  - Use of liquid chromatography-electrospray ionization-tandem mass spectrometry (LC
      ESI-MS/MS) for routine identification of enzymatically digested proteins
      separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
AB  - Automated liquid chromatography-electrospray ionization-tandem mass spectrometry
      (LC-ESI-MS/MS) analysis of >100 tryptic digests carried out on sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) separated, Coomassie Blue
      stained proteins that were prepared by >50 different laboratories demonstrates
      that a commercial electrospray/quadrupole ion trap mass spectrometer and the
      tandem mass correlation algorithm developed by Eng et al. (Am. Soc. Mass
      Spectrom. 1994, 5, 976-989) provide an extremely robust and facile approach to
      routine protein identification. By requiring a minimum of two significant matches
      to peptides that would be predicted to be produced by the protease that was used,
      low pmol levels of proteins can be identified with high confidence while
      minimizing the probability of identifying the protease itself and/or the
      ubiquitous contaminant, keratin. Hence, in only 7% of the digests analyzed was
      keratin identified and in only 5% of the digests analyzed was the protease itself
      identified. In contrast, 58% of the analyzed samples were identified and, in many
      instances, multiple proteins were identified in the same sample. Although the
      median amount of digest analyzed was 6.1 pmol, the limit of sensitivity (as the
      instrument is configured with a flow rate of 4 microL/min) appears to be at the
      500 fmol level. Since one of the primary reasons for not identifying a sample is
      that its sequence is not yet in the database searched, the utility of an LC MS/MS
      approach to protein identification will certainly increase in the future as the
      sequences of more genomes are completed.

PMID- 9638952
TI  - The emotional motor system in relation to the supraspinal control of micturition
      and mating behavior.

PMID- 9638953
TI  - Premature ejaculation and serotonergic antidepressants-induced delayed
      ejaculation: the involvement of the serotonergic system.
AB  - Premature ejaculation has generally been considered a psychosexual disorder with
      psychogenic aetiology. Although still mainly treated by behavioural therapy, in
      recent years double-blind studies have indicated the beneficial effects of some
      of the serotonergic antidepressants (SSRIs) in delaying ejaculation. We describe
      here the neurophysiology and the peripheral neuroanatomy of ejaculation and
      provide a review of the involvement of serotonin in the central nervous system in
      relation to serotonergic nuclei and their projections. A hypothesis of the role
      of 5-HT1A and 5-HT2C receptors in premature ejaculation is postulated.

PMID- 9638954
TI  - The central nervous system control of micturition in cats and humans.
AB  - Recent findings concerning the central control of micturition in cats are
      compared to findings obtained from dynamic imaging studies in humans. In the cat,
      three areas in the brainstem and diencephalon are specifically implicated in the
      control of micturition: (1) Barrington's nucleus or the pontine micturition
      center in the dorsomedial pontine tegmentum directly excites bladder motoneurons
      and indirectly inhibits, via inhibitory interneurons in the medial sacral cord,
      urethral sphincter motoneurons; (2) the periaqueductal grey receiving bladder
      filling information; and (3) the pre-optic area of the hypothalamus possibly
      involved in determining the beginning of micturition. According to PET-scan
      studies, in humans the same supraspinal regions are active during micturition. In
      the cat another area, located in the ventrolateral pontine tegmentum and is
      called the L-region, which controls the motoneurons of the pelvic floor,
      including the external urethral sphincter. This region might be considered as the
      pontine storage center. In humans the L-region is especially active in volunteers
      who tried but did not succeed to micturate. The results suggest that in cats and
      humans at the brainstem and diencephalic levels micturition is organized in the
      same way.

PMID- 9638955
TI  - Developmental and injury induced plasticity in the micturition reflex pathway.
AB  - The storage and periodic elimination of urine are dependent upon neural circuits
      in the brain and spinal cord that co-ordinate the activity of the urinary
      bladder, the urethra and the striated urethral sphincter. This study utilized
      anatomical, electrophysiological and pharmacological techniques to examine: (1)
      the organization of the parasympathetic excitatory reflex mechanisms that control
      the urinary bladder of the rat and the cat; and (2) the changes in these reflexes
      during postnatal development and after spinal cord injury. In normal adult cats
      and rats, the parasympathetic excitatory input to the bladder is dependent upon a
      spinobulbospinal reflex pathway that is activated by myelinated (Adelta) bladder
      afferents and that passes through an integrative center (the pontine micturition
      center, PMC) in the rostral brain stem. Transneuronal tracing studies using
      pseudorabies virus as well as physiological methods have revealed that the PMC is
      located in close proximity to the locus coeruleus. Single unit recordings
      indicate that neurons in the PMC respond to afferent input from the bladder and
      are excited prior to or during reflex bladder contractions. Glutamic acid is the
      major excitatory transmitter in the micturition reflex pathway. Glutamatergic
      transmission which is mediated by AMPA/kainate and NMDA receptors can be
      modulated by a variety of other transmitters. In neonatal animals, a spinal
      micturition reflex is activated by somatic afferent fibers from the perigenital
      region. This reflex is suppressed during postnatal development, but can be
      unmasked in adult animals following spinal cord injury. Spinal injury also causes
      the emergence of a spinal bladder-to-bladder reflex which in the cat is activated
      by capsaicin-sensitive C-fiber bladder afferents. Patch clamp studies in spinal
      cord slice preparations indicate that developmental and spinal cord injury
      induced plasticity in sacral parasympathetic reflex pathways is due in part to
      alterations in glutamatergic excitatory transmission between interneurons and
      preganglionic neurons. Changes in the electrical properties of bladder afferent
      pathways may also contribute to the reorganization of bladder reflexes in
      paraplegic animals.

PMID- 9638956
TI  - Neuromodulation: urodynamic effects of sacral (S3) spinal nerve stimulation in
      patients with detrusor instability or detrusor hyperflexia.
AB  - The aim of this study was to determine the urodynamic effects of sacral (S3)
      nerve stimulation in patients with urge incontinence due to detrusor overactivity
      which has been refractory to conservative treatment. A total of 24 patients with
      idiopathic detrusor instability and five with neurogenic hyperreflexia were
      studied urodynamically before and 6 months after a permanent S3 foramen electrode
      implant. The urodynamic studies at follow-up were done with the stimulus on.
      Clinically, the average voiding frequency, the number of leakage episodes and pad
      use per 24 h decreased significantly. Improvement in several urodynamic
      parameters was noted. In the idiopathic as well as in the neurogenic group, the
      correlation between symptomatic and urodynamic improvement was incomplete.
      Neuromodulation leads to improvement of several urodynamic parameters in patients
      with urge incontinence due to detrusor overactivity which has been refractory to
      conservative treatment and appears to be a valuable treatment option in these
      patients.

PMID- 9638957
TI  - Clinical studies of cerebral and urinary tract function in elderly people with
      urinary incontinence.
AB  - Brain and urinary tract function have been studied in a group of 128 geriatric
      patients with established urinary incontinence. Median age was 79 years. About
      half suffered from dementia. A group of 27 continent patients of similar age and
      cognitive status was used in some comparisons. It was expected that impaired
      voluntary control of voiding (urge incontinence) would be associated with
      particular aspects of cognitive impairment and dysfunction of specific regions of
      the brain. Comprehensive investigations, including 24 h monitoring of
      incontinence, videourodynamic testing, cognitive testing and SPECT brain
      scanning, demonstrated that genuine urge incontinence could be proven in half of
      the patients and was frequently accompanied by reduced sensation of bladder
      filling, especially in males. Genuine urge incontinence with reduced bladder
      filling sensation led to greater urine loss than other types of incontinence.
      Overall, cognitive function was slightly more impaired in patients with genuine
      urge incontinence, but the strongest and most specific association was with
      impaired temporal orientation. Genuine urge incontinence with reduced bladder
      filling sensation was associated with global underperfusion of the cerebral
      cortex and more specifically, with underperfusion of the frontal areas of the
      brain, especially on the right. These results are consistent with PET scan
      observations of Blok et al. (Brain 1997;20:112-121), which show that areas in the
      right anterior cingulate gyrus and right inferior frontal gyrus are involved in
      voluntary voiding of normal males.

PMID- 9638958
TI  - Sensory and motor components of reproductive behavior: pathways and plasticity.
AB  - Reproductive behavior in most mammalian species consists of a highly stereotyped
      pattern of movements, is elicited by specific sensory stimuli and is sex steroid
      dependent. The present paper describes a concept of the pathways in the midbrain,
      brainstem and spinal cord which control the receptive posture of the female cat.
      The midbrain periaqueductal gray (PAG), which is an important structure in the
      Emotional Motor System (EMS), receives direct input from a distinct group of
      neurons in the dorsal horn of the lumbosacral cord. This cell group overlaps with
      the location of pelvic and to lesser extent, pudendal nerve primary afferents,
      which convey information from the pelvic viscera and sex organs to the central
      nervous system. The PAG, in turn, controls various motor components of female
      receptive behavior using different pathways. For example, immobility, which is
      one of the characteristics of receptive behavior, might be mediated by a diffuse
      pathway from the PAG, via the ventral part of the medial medullary tegmentum, to
      all parts of the spinal ventral horn. More specific components, such as hindlimb
      treading, lateral deviation of the tail and elevation of the lower back, are
      thought to be controlled by a circumscribed projection from the PAG to the
      nucleus retroambiguus (NRA). The NRA is a group of interneurons at the transition
      between brainstem and spinal cord and projects directly to distinct lumbosacral
      motoneuronal cell groups, which innervate muscles that are likely to be involved
      in the female receptive posture. Estrogen induces axonal sprouting of the NRA
      lumbosacral pathway in adult female cats, which explains why female cats only
      display receptive behavior when estrogen levels are high.

PMID- 9638959
TI  - Mapping of neural and signal transduction pathways for lordosis in the search for
      estrogen actions on the central nervous system.
AB  - Estrogen can act on the brain to regulate various biological functions and
      behavior. In attempts to elucidate the estrogen action, the rodent female
      reproductive behavior, lordosis, was used as a model. Lordosis is an estrogen
      dependent reflexive behavior and, hence, is mediated by discrete neural pathways
      that are modulated by estrogen. Therefore, a strategy of mapping the pathways,
      both neural and biochemical, and examining them for estrogen effect was used to
      localize and subsequently analyze the central action of estrogen. Using various
      experimental approaches, an 'inverted Y-shaped' neural pathway both sufficient
      and essential for mediating lordosis was defined. The top portion is a descending
      pathway conveying the permissive estrogen influence which originated from
      hypothalamic ventromedial nucleus relayed via midbrain periaqueductal grey down
      to medullary reticular formation, the top of the spino-bulbo-spinal reflex arc at
      the bottom. This estrogen influence alters the input-output relationship,
      shifting the output toward more excitation. With this shift in output, estrogen
      can enable the otherwise ineffective lordosis-triggering sensory stimuli to
      elicit lordosis. In the ventromedial nucleus, the origin of the estrogen
      influence, a multidisciplinary approach was used to map intracellular signaling
      pathways. A phosphoinositide pathway involving a specific G protein and the
      activation of protein kinase C was found to be involved in the mediation of
      lordosis as well as a probable target of the permissive estrogen action. The
      action of estrogen on this signal transduction pathway, a potentiation, is
      consistent with and, hence, may be an underlying mechanism for the estrogen
      influenced shift toward excitation. Thus, further investigation on this specific
      signal transduction pathway should be helpful in elucidating the action of
      estrogen on the brain.

PMID- 9638960
TI  - Neural activation following sexual behavior in the male and female rat brain.
AB  - Neural activation following sexual behavior was studied in the male and female
      rat brain, using Fos-immunoreactivity (Fos-IR) as a measure. In accordance with
      the available literature, we observed increased expression of c-fos in the medial
      preoptic nucleus (MPN), in the posteromedial subdivision of the bed nucleus of
      the stria terminalis, in the posterodorsal part of the medial amygdala, and in
      the caudal thalamus, in the parvicellular part of the subparafascicular nucleus.
      After performance of different behavioral elements (anogenital investigation,
      mounting, intromission or ejaculation) not only the numbers of Fos-IR neurons
      varied considerably, but also their distribution. Especially after ejaculation,
      but in females already after intromissions, dense groups of Fos-IR neurons
      appeared in specific subdivisions of the areas mentioned above. That these groups
      of dense Fos-IR appeared as a result of the ejaculation per se, was assessed by
      administrating the 5-HT1A agonist 8-OH-DPAT to the males, whereupon they
      ejaculated within a few seconds, without the usual amount of preceding behavioral
      elements. Since the pattern of Fos-IR was similar to the normal ejaculation
      pattern, we have described the dense activation areas as 'ejaculation-related
      clusters'. Our review discusses the stimuli and pathways probably involved in the
      observed pattern of Fos-IR and we conclude that the 'deep viscero-genital'
      activation, occurring at the moment of ejaculation, running along the pelvic
      nerve and ascending from the spinal cord, is most probably responsible. We show
      that the location of the Fos-IR neurons in the medial subparafascicular nucleus
      perfectly coincides with the location of Galanin-IR fibers, ascending from the
      spinal cord. The application of anterograde and retrograde neuroanatomical
      tracers into the MPN, in combination with Fos-IR showed that the medial preoptic
      nucleus has very specific relationships with the Fos-IR sub-areas, involved in
      ejaculation. We conclude that within the larger brain structures involved in
      sexual and other social activities, a specific ejaculation-related subcircuit
      exists, which may, under normal conditions in the rat, serve a 'sexual-satiety
      function'.

PMID- 9638961
TI  - Organization and regulation of sexually dimorphic neuroendocrine pathways.
AB  - Reproduction depends on the co-ordinated expression of stereotypical behaviors
      and precisely timed physiological events, yet the neurobiological mechanisms
      underlying the integration of sensory and hormonal information that is crucial to
      this process have remained difficult to define. A variety of experimental
      approaches has provided compelling evidence that the anteroventral
      periventricular nucleus (AVPV) of the preoptic region plays a particularly
      important role in the neural control of gonadotropin secretion. It is larger in
      female rats, contains high densities of neurons that express receptors for
      ovarian steroid hormones and appears to provide direct projections to
      gonadotropin releasing hormone neurons in the hypothalamus. Moreover, it receives
      inputs from a variety of distinct sensory systems known to influence secretion of
      luteinizing hormone from the anterior pituitary. Thus, the AVPV appears to
      represent an important nodal point in sexually dimorphic forebrain circuits for
      the integration of sensory and hormonal information that influence reproduction.
      Examples of neurohumoral integration at the level of functional neural systems,
      individual neurons in the AVPV, or at the molecular level have been identified
      which provide new insight into how the hypothalamus co-ordinates expression of
      sex specific reproductive behaviors with gonadotropin secretion.

PMID- 9638962
TI  - Double duty for sex differences in the brain.
AB  - Sex differences have been found in the anatomy of brains of a wide variety of
      vertebrates including humans. Common lore tells us that sex differences in the
      brain cause sex differences in behavior. This review entertains the possibility
      that sex differences in the brain may also do the exact opposite. Specifically,
      sex differences may allow males and females to display remarkably similar
      behaviors, despite major differences in their physiological and hormonal
      conditions. First, the difficulties in interpreting the relationship between
      structure and function will be illustrated by discussing the role of the sexually
      dimorphic medial preoptic area (MPOA) in male sexual behavior and parental
      behavior. Second, the sexually dimorphic vasopressin innervation of the brain
      will be presented as a system that appears to promote as well as prevent sex
      differences in behavior. Finally, basic and clinical aspects of sex differences
      in human brains will be discussed.

PMID- 9638963
TI  - Comparison of endothelin-1 levels at rest and during exercise between patients
      with cardiac syndrome-X and healthy people.
AB  - Several previous studies have shown that endothelin-1 (ET 1) plasma levels are
      raised in cases of endothelial abnormality and microvascular dysfunction.
      Syndrome-X constitutes an important clinical entity characterized by angina-like
      pain and normal coronary arteries which is believed to reflect microvascular
      dysfunction. The aim of the present study was to investigate the role of ET 1 in
      the pathophysiology of the above syndrome. For that purpose the plasma ET 1
      concentrations, measured by radioimmunoassay, between 28 X-syndrome patients
      (group A) and 10 age-matched normal control subjects (group B) at rest and at the
      peak of the exercise testing were compared. We specify that all individuals of
      group A were referred to our Department for effort angina and were found to have
      normal coronary arteriograms, negative ergonovine and hyperventilation test and
      positive exercise test. Our results showed that while at rest ET 1 plasma
      concentrations did not differ significantly between the two groups, at the peak
      of the exercise test its levels were found to be significantly higher in syndrome
      X patients as compared with those of normal subjects (p< 0.001). In addition, in
      healthy control subjects ET 1 levels decreased during exercise as compared with
      the baseline values and that difference was found to be statistically significant
      (p approximately 0.01). The above finding suggests opposite kinetics during
      exercise of ET 1 between the two groups studied, which could explain effort
      angina onset in patients with syndrome-X.

PMID- 9638964
TI  - Simvastatin compared to fluvastatin in the reduction of serum lipids and
      apolipoproteins in patients with ischaemic heart disease and moderate
      hypercholesterolaemia.
AB  - OBJECTIVE: Inhibitors of HMG-CoA reductase are widely used for the treatment of
      hypercholesterolaemia and have recently been shown in the Scandinavian
      Simvastatin Survival Study (4S), to reduce coronary mortality as well as total
      mortality in CH D patients. Although a couple of studies have already established
      the efficacy ratio between simvastatin and fluvastatin, one of the newest members
      of this class, we considered it to be important to verify the comparative
      efficacy in patients with coronary artery disease in the same type of patients
      that were included in 4S particularly since the previous studies include rather
      few patients with CHD, 17-28% only. METHODS AND RESULTS: Three Scandinavian lipid
      clinics participated in this randomized double-blind study and enrolled a total
      of 113 hypercholesterolaemic patients with a profile similar to the 4S patients,
      i.e. either a history of typical angina pectoris lasting at least three months or
      a myocardial infarction at least six months before the study and with moderate
      hypercholesterolaemia, total serum cholesterol between 5.5 and 8.0 mmol/l. After
      a diet run-in period lasting at least 8 weeks, followed by a two week placebo
      period, patients received treatment with active drug for a 16 week period, with
      measurement of lipids using the same technique and laboratory as was used in 4S.
      Patients were randomly assigned to simvastatin 20 mg or fluvastatin 20 mg. If
      after 6 weeks of double-blind treatment, the 4S total cholesterol target of < or
      = 5.2 mmol/l total serum cholesterol had not been reached, the dose was doubled
      at the next visit, i.e. at week 10 based upon blinded titration information from
      the central lipid laboratory like in the 4S study. A final assessment of serum
      lipids and lipoproteins was made at week 16. The mean percent reductions in LDL
      cholesterol from baseline were 37% and 40% in the simvastatin group compared to
      19% and 26% in the fluvastatin group, at weeks 10 and 16, respectively (p <
      0.001). In the simvastatin group 18 percent of the patients needed an increase in
      the dose to 40 mg compared to 63 percent in the fluvastatin group (p < 0.001). At
      the 20 mg dosage, simvastatin produced a lowering of LDL-cholesterol
      approximately twice that of fluvastatin 20 mg and resulted in 82% of patients
      achieving the cholesterol target levels as defined in the 4S study, compared to
      19% for fluvastatin. All other recorded lipid variables showed differences which
      favoured simvastatin over fluvastatin at comparable doses including serum
      triglyceride reductions where serum triglycerides at week 6 were borderline
      significantly different between the two groups. Patient tolerability of the two
      drugs was similar. CONCLUSION: At the recommended doses in patient with angina or
      a prior MI and mild to moderate hypercholesterolaemia simvastatin is considerably
      more effective than fluvastatin in lowering serum total cholesterol, LDL
      cholesterol as well as other serum lipid risk factors. At an average titrated
      dose of 32 mg less than 50% of the fluvastatin patients reached the 4S
      cholesterol target of < 5.2 mmol/l compared to 89% of the simvastatin patients at
      an average dose of 23 mg daily and only 13% of the fluvastatin patients achieved
      an LDL-cholesterol reduction of at least 40% compared to 63% of the simvastatin
      patients.

PMID- 9638965
TI  - The use of low-molecular-weight heparins in cardiovascular disease.
AB  - Unfractionated heparin (UFH) has been used for decades as an effective and
      relatively inexpensive agent in the prevention of venous and arterial
      thromboembolic events. Low-molecular-weight heparin (LMWH) preparations are
      obtained by chemical or enzymatic depolymerization of unfractionated commercial
      grade heparin; their mean molecular weights range from below 4,000 to about 6,500
      D (Table 1). Their mechanism of antithrombotic action is basically similar to
      that of UFH - binding to antithrombin to inhibit activated coagulation factors -
      but they have a different relative potency (to some extent also inter
      individually) of anti-Xa versus anti-IIa activity. Shorter fragments which
      contain the essential pentasaccharide to bind to antithrombin but lack the
      required chain length to bind at the same time to thrombin, only inhibit
      activated Factor X. Fragments above 5,000 D which contain the pentasaccharide
      maintain their property to inhibit Factor Xa but with increasing chain length,
      they become stronger inhibitors of thrombin. LMWHs have little or no effect on
      global tests of blood coagulation such as the activated partial thromboplastin
      time when used in prophylactic or therapeutic dosages. A specific assay of anti
      Xa activity is required to monitor biological activity but this is rarely needed.
      The main advantage of LMWHs for clinical practice derive from their
      pharmacokinetic properties. UFH binds to plasma proteins, endothelial cells and
      platelets. This saturable mechanism clears heparin rapidly from the circulation
      (the plasma half-life is non-linearly dose-related) and is held responsible for
      the large variation from person to person and from moment to moment in biological
      and clinical response. LMWHs bind far less to these elements and therefore have a
      2 to 4-times longer plasma half-life, a markedly better bioavailability when
      injected subcutaneously and a more stable dose response. They also have a lower
      toxic effect in terms of heparin-induced thrombocytopenia which may be related to
      their lesser interaction with platelets.

PMID- 9638966
TI  - Sudden death in hypertrophic cardiomyopathy: risk stratification and prevention.
AB  - Hypertrophic cardiomyopathy is an important cause of sudden death in young and
      asymptomatic patients. Young athletes and patients with unexplained sudden death,
      including their relatives, should be screened for its presence. Risk
      stratification identifies a high-risk group, in which preventive measures should
      be taken to reduce the risk for sudden death: moderate to heavy physical activity
      has to be avoided and arrhythmias with haemodynamic impact should be rigorously
      prevented.

PMID- 9638967
TI  - Left atrial lipoma: case report and review of the literature.

PMID- 9638968
TI  - Magnetic resonance imaging in a patient with a dual-chamber pacemaker.
AB  - The presence of an implanted cardiac pacemaker has been considered an absolute
      contraindication for magnetic resonance imaging due to the interactions between
      the pulse generators and the magnetic and radiofrequency fields generated by the
      magnetic resonance unit. We describe the case of a patient with a dual-chamber
      pacemaker who underwent two magnetic resonance imaging examinations of the head
      without any sequelae. Both procedures were performed with a 1 Tesla unit, with
      the pacemaker programmed to the AOO mode. The only interference observed was
      activation of the reed switch -probably due to the static magnetic field-
      resulting in asynchronous atrial pacing at the magnet rate. Although the general
      policy of never exposing a patient with a pacemaker to magnetic resonance imaging
      should not be revised, we think that if the testing is considered essential, it
      could be safely used in certain carefully selected patients.

PMID- 9638969
TI  - Cardiac graft vasculopathy: aetiologic factors and therapeutic approaches.
AB  - Heart transplantation has become an accepted and successful treatment for end
      stage heart disease with survival rates of 80-90% after one year and 70% after 5
      years. During the early posttransplant period (6-12 months), patients are subject
      to two major complications: rejection and infection. Fortunately, a certain
      degree of graft tolerance develops, allowing the immunosuppressive therapy to be
      progressively tapered off with a concomitant decrease in infectious problems.
      Long-term survival, however, is largely dependent on the development of an
      accelerated atherosclerosis in the graft, which is believed to represent some
      kind of chronic rejection. This transplant vasculopathy is documented by means of
      coronary angiography with an incidence of approximately 5 to 10% per year. It is
      not surprising therefore that major interest has risen concerning risk factors
      promoting this pathology.

PMID- 9638970
TI  - Non-fatal sustained ventricular fibrillation.

PMID- 9638971
TI  - Structure and function of P-selectin glycoprotein ligand-1.
AB  - Directed emigration of leukocytes into inflammatory sites and lymphatic tissues
      is orchestrated by the regulated expression of adhesion and signaling molecules
      on cells within the vasculature. The selectin family of adhesion molecules that
      are expressed on activated endothelial cells (E-selectin and P-selectin),
      activated platelets (P-selectin), and peripheral blood leukocytes (L-selectin),
      mediate tethering and rolling of leukocytes to the vessel wall in the
      microcirculation. Selectins promote these interactions by binding to
      glycoconjugate ligands expressed on apposing cells. Selectin-mediated rolling is
      a prerequisite for firm adhesion and subsequent transendothelial migration of
      leukocytes into tissues. This review will focus on the structure and function of
      P-selectin glycoprotein ligand-1 (PSGL-1, CD162). PSGL-1 is a disulfide-bonded
      homodimeric mucin-like glycoprotein on leukocytes that interacts with P-, L-, and
      E-selectin. PSGL-1 mediates leukocyte-endothelial and leukocyte-platelet adhesion
      by binding to P-selectin expressed on activated endothelium and platelets and
      PSGL-1 mediates leukocyte-leukocyte adhesion by binding to L-selectin expressed
      on apposing leukocytes. PSGL-1 is unique in that it is the only selectin
      glycoprotein ligand that has been directly demonstrated to mediate cell-cell
      adhesion in vitro and in vivo.

PMID- 9638972
TI  - Therapy-related chronic myeloid leukemia: an epidemiological, clinical and
      pathogenetic appraisal.
AB  - Second primary cancers represent an important complication of modern chemotherapy
      and radiotherapy. Therapy-related (tr) leukemias are among the most common second
      malignancies in both pediatric and adult populations. Whereas a reasonable amount
      of data is available regarding the epidemiology, molecular pathogenesis, clinical
      behavior and response to therapy of second primary acute leukemias, very little
      is known about therapy-related chronic myeloid leukemia (tr-CML). A better
      characterization of this entity could increase our understanding about the
      mechanisms of carcinogenesis, specially the induction of specific genetic
      abnormalities, e.g., BCR-ABL fusion, following chemotherapy and/or radiotherapy
      exposure, could facilitate the investigation of the kinetics of the development
      of CML, and also provide a model to study molecular events that might precede its
      development. Review of 32 tr-CML cases suggests that there are no clinically
      appreciable differences between tr-CML and de novo CML cases. Analysis of large
      epidemiological studies that investigated the risk of second primary leukemias
      has not shown any clear evidence of a higher risk of CML among individuals who
      underwent treatment for a primary cancer over the general population. The cancer
      predisposing syndromes, the detection of BCR-ABL transcripts in healthy
      individuals, and the induction in vitro of BCR-ABL fusions by ionizing radiation,
      are all discussed in the context of tr-CML. Finally, the need for a large
      epidemiological study to specifically assess the risk of developing second
      primary CML after chemotherapy and/or radiotherapy is stressed.

PMID- 9638973
TI  - CDKN2 (MTS1/p16INK4A) gene alterations in adult T-cell leukemia/lymphoma.
AB  - p16INK4A is a cyclin-dependent kinase inhibitor (CDKI), and regulates the cell
      cycle negatively. Recently, p16INK4A protein was shown to be encoded by the CDKN2
      gene, which is identical to multiple tumor suppressor gene 1 (MTS1) on chromosome
      9p21, where genetic alterations occur frequently in many malignant tumors. As the
      loss of p16INK4A function by genetic alterations leads to inappropriate
      progression of the cell cycle, the CDKN2 gene has been investigated intensively
      as a new candidate tumor suppressor gene in many malignant tumors. Adult T-cell
      leukemia/lymphoma (ATLL) is a peripheral T-cell malignancy associated with human
      T-cell lymphotrophic virus type 1 (HTLV-1). As the development to ATL is believed
      to require not only HTLV-1 infection but also accumulation of genetic
      alterations, we investigated the relationship between alterations in the CDKN2
      gene and ATL. Alterations in the CDKN2 gene were detected in approximately 15 to
      20% of ATL patients. Interestingly, most of the patients with CDKN2 gene
      alterations had the aggressive form of ATL. The CDKN2 gene appears to be the
      major tumor suppressor gene on chromosome 9p21, and alteration in this gene may
      play an important role during late stages in the transformation process induced
      by HTLV-1.

PMID- 9638974
TI  - CD73 and adhesion of B-cells to follicular dendritic cells.
AB  - CD73, otherwise known as ecto-5'-nucleotidase, is a lymphocyte maturation marker
      which is involved in intracellular signalling, lymphocyte proliferation and
      activation. In addition, we have demonstrated that CD73 is involved in mediating
      lymphocyte binding to in vitro cultured endothelial cells and in controlling
      adhesion between freshly isolated germinal center B-cells and follicular
      dendritic cells (FDC). In secondary lymphoid tissues, CD73 is expressed on FDC in
      the light zone of the germinal center as well as on small, resting mantle zone B
      cells but not on B-cells within germinal centers. In this review article, the
      potential role of CD73 in controlling B-cell-FDC interactions and B-cell
      maturation will be discussed.

PMID- 9638975
TI  - Growth characteristics of myelodysplastic CD34+ cells.
AB  - Myelodysplastic syndromes (MDS) are a heterogeneous group of disorders of
      hematopoiesis entailing hyperproliferative and ineffective hematopoiesis
      associated with morphologic evidence of marrow cell dysplasia resulting in
      refractory cytopenia(s), and an increased risk of transformation into acute
      myeloblastic leukemia (AML). The administration of colony-stimulating factor(s)
      (CSFs) to patients with MDS increased blood neutrophil concentrations, in most
      patients, and it was anticipated to be of benefit to prevent infections. The
      progression to AML while being treated with CSFs has come under close scrutiny.
      In vitro studies are expected to produce more pertinent criteria for selection of
      patients who are likely to benefit, as well as the overall benefits of various
      therapies. For this purpose, in vitro colony assays are an excellent approach for
      investigation of the biologic characteristics of MDS progenitor cells. The stem
      cell phenotype CD34 is the one of the best markers of progenitor cells, and can
      be used for the purification of these cells to unify levels of maturation; a
      direct comparison of proliferative and differentiative capacity of MDS progenitor
      cells with normal CD34+ cells can thus be made. The properties of MDS CD34+ cells
      are described here in association with proliferation and differentiation, with
      special emphasis on the role of stem cell factor (a ligand for c-kit) in leukemic
      type growth of MDS CD34+ cells.

PMID- 9638976
TI  - Regulation of myeloid and lymphoid development of hematopoietic stem cells by
      bone marrow stromal cells.
AB  - Development of hematopoietic stem cells is regulated by stromal cells of the bone
      marrow. Many stromal cell lines have been established from temperature-sensitive
      SV40 large T-antigen gene transgenic mice and used to examine regulation of the
      purified stem cells. When the sorted stem cells were cocultured on the stromal
      cell layers, cobblestone formation was induced by the stromal cells. The
      cobblestones were formed by finite cell division (8 divisions on average) of
      sorted Lin- c-Kit+ Sca1+ stem cells committed to myeloid or lymphoid lineages.
      These stromal cell lines showed variable activities supporting the stem cell
      development. In one stromal cell line, TBR59, two waves of cobblestone formation
      committed to either myeloid lineage or lymphoid lineage were induced. TBR31-1,
      another bone marrow stromal cell line, induced only the cobblestone formation
      committed to lymphoid lineage. These results indicate that the bone marrow
      stromal cells selectively induce lineage-specific commitment of the stem cells.
      Both cobblestone formations require c-Kit function as well as adhesive
      interaction through VLA4 and VCAM1.

PMID- 9638977
TI  - Production and effects of interleukin-6 and other cytokines in patients with non
      Hodgkin's lymphoma.
AB  - Cytokines are regulatory molecules that are produced by a variety of cell types
      and are characterized by numerous biologic functions involved in the regulation
      of the immune system and hematopoiesis. This review summarizes the functions and
      regulation of cytokines in lymphomas and discusses the effect of a specific
      cytokine, interleukin-6 (IL-6), in B-cell lymphomas. IL-6 is a multipotent
      cytokine that can mediate the differentiation of B-cells into immunoglobulin
      secreting cells, stimulate the autocrine or paracrine growth of myeloma cells,
      induce acute-phase proteins in liver cells, and may influence the pathogenesis of
      several diseases by autocrine or paracrine mechanisms. Patients with non
      Hodgkin's lymphoma (NHL) have increased serum concentrations of IL-6; increased
      IL-6 levels can be associated with the presence of B-symptoms. Data presented in
      this review indicate that neoplastic cells from patients with NHL contained high
      concentrations of IL-6. Thus, elevated serum levels of IL-6 appear to originate
      from the lymphoma cells in patients with B-cell NHL, suggesting that the
      neoplastic cells may modulate the general status of patients with B-cell NHL. The
      inhibition or modification of the production of IL-6 in lymphoma cells may lead
      to a more effective control of the general status of patients with B-cell NHL.

PMID- 9638978
TI  - The tumor necrosis factor signaling complex: choosing a path toward cell death or
      cell proliferation.
AB  - Signal transduction pathways which are initiated by the tumor necrosis factor
      (TNF) utilize receptors which are devoid of intrinsic catalytic activity.
      Recently identified two families of proteins that directly associate with the
      cytoplasmic domains of the TNF receptor family members, have partially bridged a
      molecular gap within the TNF-induced signaling pathways. Clearly, there are
      numerous alternate routes that originate from the TNF ligand-receptor assembly
      and terminate on the diverse cellular responses, including proliferation,
      differentiation, or death. This review focuses on recent advances characterizing
      the TNF ligand-receptor signaling network, which allow to better understand its
      participation in a life-death balance within the target cell.

PMID- 9638979
TI  - Analysis of the t(2;5) (p23;q35) translocation in CD30+ primary cutaneous
      lymphoproliferative disorders and Hodgkin's disease.
AB  - The t(2;5) (p23;q35) chromosomal translocation is found in about 40% of lymph
      node-based CD30+ anaplastic large cell lymphomas of T-cell or null-cell lineage.
      This translocation results in the expression of a fusion protein containing the
      catalytic domain of anaplastic lymphoma kinase (ALK) under the control of the
      promoter for nucleophosmin (NPM), a nucleolar phosphoprotein. Expression of ALK
      activity, normally absent in lymphocytes, is postulated to be involved in the
      pathogenesis of lymphomas bearing the t(2;5) translocation. Certain primary
      cutaneous lymphoproliferative disorders and Hodgkin's disease are also known to
      contain CD30+ large lymphoid cells. In order to determine the role of the t(2;5)
      translocation in these diseases, several investigators have employed a variety of
      techniques including cytogenetics, genomic Southern blot analysis, RNA- and DNA
      based PCR assays, various forms of in-situ hybridization, and immunostaining for
      the p80 fusion protein encoded by the chimeric t(2;5) transcripts. These studies
      included approximately 415 cases of Hodgkin's disease, 65 cases of CD30+ primary
      cutaneous large cell lymphoma, and 38 cases of lymphomatoid papulosis. The
      aggregate results of these studies indicate that the t(2;5) translocation or
      other somatic mutations resulting in inappropriate expression of ALK are involved
      rarely if at all in the pathogenesis of Hodgkin's disease, but may be present in
      about 10% of cases of lymphomatoid papulosis and 20% of cases of CD30+ primary
      cutaneous large cell lymphoma. However, the t(2;5) has not been detected yet in
      any case involving multiple or secondary CD30+ lymphoproliferative disorders,
      thereby providing no evidence for a role in tumor clone progression. Additional
      studies will be needed to determine if t(2;5) status has any clinical
      significance for patients with CD30+ primary cutaneous lymphoproliferative
      disorders.

PMID- 9638981
TI  - Enhanced proliferative activity of PIXY-321, the granulocyte-macrophage colony
      stimulating factor and interleukin-3 fusion protein.
AB  - Previous studies with the granulocyte-macrophage colony-stimulating factor (GM
      CSF) and interleukin-3 (IL-3) fusion protein, PIXY-321, demonstrated the enhanced
      biological activity of this molecule in comparison with GM-CSF or IL-3 alone or
      in combination. Here, we performed experiments to determine the proliferative
      effect of PIXY-321 on 13 constitutively growth factor-dependent human leukemia
      cell lines in comparison with GM-CSF, IL-3 and their combination using as read
      out parameters the 48-hour 3H-thymidine incorporation assay and viable cell
      counts after in vitro culture for 7-8 days. Whereas one cell line was not
      responsive to any of these three cytokines, the other 12 cell lines showed
      variable degrees of growth in response to these effector molecules. PIXY-321
      increased proliferation as measured by thymidine uptake relative to IL-3, GM-CSF
      or GM-CSF + IL-3 by 34% (range 5-448%), 12% (range 0-122%), and 6% (range 1-13%),
      respectively. PIXY-321 induced a mean increase of 32%, 30% and 11% in cell counts
      relative to the values obtained with IL-3, GM-CSF or GM-CSF + IL-3, respectively.
      Altogether, these data indicate that PIXY-321 stimulates proliferation of
      immature hematopoietic cells substantially better than equivalent concentrations
      of the single growth factors GM-CSF and IL-3. This hybrid growth factor showed a
      marginal to modest, but definite and reproducible increase in proliferation
      compared to the combination of GM-CSF plus IL-3. In summary, the fusion cytokine
      protein PIXY-321 appears to have biological effects superior to those elicited by
      its components, singly or in combination. This unique molecule should represent a
      useful tool in studies on the mechanisms underlying cytokine ligand-receptor
      interaction and the subsequent signal transduction. The use of PIXY-321 provides
      an opportunity for taking greater advantage in vitro and in vivo of the
      hematopoietic stimulatory activities of GM-CSF and IL-3.

PMID- 9638980
TI  - HIV-related non-Hodgkin's lymphoma: CHOP induction therapy and interferon-alpha
      2b/zidovudine maintenance therapy.
AB  - In a prospective multicenter study 68 out of 158 patients with HIV infection and
      malignant lymphoma were assigned to a risk-adapted induction therapy using the
      following algorithm: High-risk patients fulfilled 2 of 3 criteria: T4 lymphocytes
      <50/microL; WHO activity index 3 or 4; pre-existing AIDS-defining opportunistic
      infection. Normal-risk patients received 4 to 6 cycles of CHOP chemotherapy;
      those that achieved complete remission (CR) received zidovudine (500 mg/d) and
      interferon-alpha maintenance therapy (5 million units three times a week) for one
      year. High-risk patients received low-dose CHOP or vincristine/prednisone
      chemotherapy. Supportive care was performed with pentamidine inhalation and G
      CSF. Intrathecal (it) methotrexate was given for CNS prophylaxis. The median
      survival was 634 days for 38 patients of the normal-risk group and 129 days for
      30 patients of the high-risk group. 18 high-risk patients treated with low-dose
      CHOP had better survival (156 days) than 12 patients treated with
      vincristine/prednisone (72 days p=0.044). 68% of the patients in the normal-risk
      group achieved complete remission. 5 out of 18 high-risk patients treated with
      low-dose CHOP achieved complete remission. Three normal-risk patients developed
      fatal opportunistic infections during chemotherapy. Immune parameters
      deteriorated after CHOP induction and partially recovered with maintenance
      treatment. We conclude that the normal-risk patients survived longer than
      reported in most published studies. Toxicity was low. Low-dose CHOP seems to be
      superior to vincristine/prednisone therapy in high-risk patients.

PMID- 9638982
TI  - Gastrointestinal emergencies in patients with acute intestinal graft-versus-host
      disease.
AB  - Acute intestinal graft-versus-host disease (GVHD) develops in about 30-50% of
      allogeneic bone-marrow transplant recipients: 10-20% have gastrointestinal
      emergencies (hemorrhage or perforation). Mortality reaches 30-60% in patients
      with acute, grade 2-4 GVHD. We studied 36 bone marrow recipients in whom acute
      intestinal GVHD developed. Seven had gastrointestinal emergencies: 4 severe
      gastrointestinal bleeding and 3 acute peritonitis. Three patients with
      gastrointestinal bleeding and one patient with peritonitis responded to medical
      therapy. Three needed surgery: one with bleeding and two with peritonitis, while
      1 patient had embolization. Of the 7, two patients died, one after embolization
      and one after surgery. Two of the three surgically-treated cases are still alive
      several years after operation. From this experience we feel that surgery for
      gastrointestinal bleeding in acute GVHD is indicated only when medical treatment
      fails. Severe neutropenia, thrombocytopenia (<10.000 x mm3) and blood cultures
      positive for CMV have an unfavorable prognostic value.

PMID- 9638983
TI  - Expression of p53 predicts treatment failure in aggressive non-Hodgkin's
      lymphomas.
AB  - Approximately 50% of patients with aggressive non-Hodgkin's lymphomas (NHL)
      achieve a complete remission (CR) and cure with combination chemotherapy. The
      International Index is a useful clinical measure that predicts the patients'
      tolerance of therapy and likelihood of achieving CR, but it is not a direct
      measure of chemosensitivity. In this study we have investigated the predictive
      value of the tumor suppressor gene, p53, as a biological marker for response to
      treatment in the aggressive NHL. A retrospective study was carried out on 50
      patients with aggressive NHL who were treated with CHOP chemotherapy. Treatment
      outcome was correlated with the expression of p53 in the lymphoma, as measured by
      routine immunohistochemistry using the monoclonal antibody Do-7. Forty percent of
      the lymphomas had >5% of the cells staining positively for p53 and this finding
      correlated significantly with response to treatment. Fifty percent of patients
      with p53 positive tumors achieved a CR versus 77% of patients with p53 negative
      tumors. In addition, the relapse rate and time to relapse were significantly
      different in the two groups. In the p53 positive group, 60% of patients relapsed
      in a median time of 6 months, whereas 26% of the p53 negative group relapsed with
      the time to relapse being >22 months. The overall survival of the p53 positive
      group (17 months) was significantly shorter than that of p53 negative group (>24
      months). These results suggest that the immunohistochemical assessment of p53 is
      a simple and important prognostic measure for patients with aggressive NHL who
      are treated with CHOP chemotherapy.

PMID- 9638984
TI  - Myeloperoxidase gene expression in infant leukemia: a Pediatric Oncology Group
      Study.
AB  - A high incidence of co-expression of myeloid-associated antigens in infant B
      precursor Acute Lymphocytic Leukemia (B-ALL) has been reported, but the
      significance of this finding is uncertain. To further assess myeloid
      differentiation and its prognostic significance in this disease, we investigated
      the frequency of myeloperoxidase (MPO) gene expression in the blast cells from 43
      infants with B-ALL registered in a Pediatric Oncology Group (POG) Pilot Study for
      Treatment of Infant ALL, utilizing a molecular probe for detection of MPO
      messenger RNA (mRNA) by Northern blot hybridization and a monoclonal antibody to
      detect MPO-protein by immunohistochemical staining. Sufficient RNA for Northern
      blot was extracted from 32 bone marrow or blood samples. In two cases, MPO mRNA
      was determined by a reverse transcriptase-polymerase chain reaction assay and was
      negative in both cases. MPO-specific transcripts (MPO+) were present in 19 of 34
      (56%) samples analyzed. Immunoreactive MPO protein was positive in 13 of the 20
      (65%) patients studied. No correlation was found between MPO gene expression and
      clinical or laboratory features, karyotypic patterns or clinical outcome. The
      high frequency of MPO gene expression demonstrated in this study suggests that
      leukemogenic events in many cases of infant B-ALL appear to involve a pluripotent
      stem cell not yet fully committed to lymphoid differentiation.

PMID- 9638985
TI  - Residual leukemic cell counts in the bone marrow at the end point of intensive
      induction therapy may be a prognostic factor for acute myeloblastic leukemia in
      adults.
AB  - Between January 1990 and May 1994, 59 previously untreated adult patients with
      acute myeloblastic leukemia (AML) were treated with a combination of behenoyl
      cytosine-arabinoside (BHAC), daunorubicin (DNR), 6-mercaptopurine (6-MP) and
      prednisolone (PSL). Forty one patients (69.5%) achieved complete remission (CR).
      The Kaplan-Meier analysis revealed an actuarial probability for remaining in
      remission of 36% in patients who achieved remission and a survival of 29% in all
      patients at 5 years. A favorable factor relative to achieving CR was performance
      status (P=0.04). In addition the presence of 300 cells/microl or less of residual
      leukemic cell counts in the bone marrow at the end point of induction therapy
      tended to favor remission (P=0.06) using the multivariate analysis with a
      multiple logistic regression model. In addition the residual leukemic cells
      counts of less than 300/microl in the bone marrow at the end point of induction
      therapy was the most significant factor for durable remission (P=0.05) by the
      Cox's proportional hazard model. We concluded that residual leukemic cells counts
      in the bone marrow at the end point of intensive induction therapy is a valuable
      prognostic factor for adults receiving response-oriented individualized induction
      therapy for AML.

PMID- 9638986
TI  - High incidence of chemotherapy-induced acral erythema in female patients with non
      Hodgkin's lymphoma treated with the VACOP-B regimen.
AB  - Seven patients, all females out of 29 with non-Hodgkin's lymphoma (NHL) (16 males
      and 13 females) treated with the VACOP-B regimen utilizing granulocyte-colony
      stimulating factor (G-CSF) support developed chemotherapy-induced acral erythema
      (CAE). In contrast, none of 32 patients with NHL who were treated with CHOP,
      MACOP-B, or biweekly CHOP regimens without G-CSF developed CAE. Total dose
      intensities of VACOP-B regimen were higher than those of the three other
      regimens. However, no significant difference in dose intensities of each drug in
      the patients treated with the VACOP-B regimen was found between male and female
      patients and between female patients with or without CAE. The cause of the high
      incidence of CAE (7/13) in the female patients treated with VACOP-B regimen
      remains unknown. However, female sex hormones may increase susceptibility to CAE.
      Since the occurrence of CAE interrupts intensive chemotherapy and reduces the
      cure rate, high risk patients for CAE should be carefully monitored for early
      symptoms and signs of CAE and should be treated early and appropriately.

PMID- 9638987
TI  - Detection of B-cell monoclonality in fine needle aspiration by PCR analysis.
AB  - Cytologic examination of fine-needle aspiration (FNA) sometimes fails to diagnose
      the malignant nature of B-cell proliferations. In this study we analyzed the Ig
      gene rearrangement of 49 FNA samples by polymerase chain reaction (PCR) in order
      to evaluate whether molecular analyses can improve the accuracy of FNA. Twenty
      six patients had non-Hodgkin's lymphoma, 11 had reactive lymphoid diseases, 5 had
      chronic inflammation and 7 had carcinoma. A semi-nested PCR was performed using
      an oligoprimer specific for consensus sequences of the V regions (FR3A) and two
      oligoprimers derived from conserved sequences of the J regions (LJH and VLJH).
      Histologic examination always followed the molecular and cytologic analysis. The
      sensitivity of PCR and FNA morphological examination in detecting a neoplastic
      pattern was 92% and 78%, respectively. When samples were considered inadequate
      for cytologic examination, PCR always reached a diagnosis consistent with the
      histologic features. Our results demonstrate that PCR analysis of FNA specimens
      is a reliable and sensitive method capable of enhancing the diagnostic accuracy
      of cytologic examination.

PMID- 9638988
TI  - All trans retinoic acid with low dose cytosine arabinoside in the treatment of
      myelodysplastic syndrome.
AB  - The demonstration of synergistic interaction between differentiation inducing
      agents and DNA synthesis inhibitors suggests that these two groups act by two
      different mechanisms. We prospectively studied the response rate, response
      duration, survival, and toxicity in 10 patients with myelodysplastic syndrome
      (MDS) treated with all trans retinoic acid (ATRA) and low dose cytosine
      arabinoside (ara-C). These patients diagnosed between October 1993 and May 1995
      were treated with ATRA (45 mg/M2/day) for 90 days followed by 90 mg/M2 on
      alternate day till Day 275; together with Ara-C (10 mg/m2) subcutaneously twice
      daily for 21 days for a total of 6 cycles. These patients were analyzed for
      response after 3 cycles of LD Ara-C and at the time of completion of therapy.
      Toxicity was recorded at the end of each cycle of Ara-C. There were 6 male and 4
      female patients in the age range of 24 to 76 years. The morphological diagnosis
      was chronic myelomonocytic leukemia in 2, refractory anemia with excess blasts in
      4 and refractory anemia with excess blasts in transformation in 4. Only 1 patient
      achieved a complete remission and 1 patient achieved a partial response. Four
      patients had progressive disease on treatment. One patient died of neutropenic
      sepsis and 1 of resistant thrombocytopenia and intracranial hemorrhage while on
      treatment. One patient refused further treatment after a minor clinical response
      and in 1 patient treatment was stopped due to toxicity. This data in a pilot
      study with a limited number of patient suggests that ATRA in combination with Ara
      C has little effect in MDS.

PMID- 9638989
TI  - Familial hairy cell leukemia.
AB  - Familial hairy cell leukemia (HCL) occurs rarely, and HCL occurring in
      association with other hematologic malignancies is even rarer. We describe two
      cases of familial HCL syndromes: a mother and son with HCL, and a HCL patient
      whose aunt developed Hodgkin's Disease (HD). This is the first reported familial
      association of HCL with HD.

PMID- 9638990
TI  - Mediastinal large-cell lymphoma with sclerosis refractory to conventional
      chemotherapy can respond after daily oral cyclophosphamide.
AB  - Mediastinal large-cell lymphoma with sclerosis (MLCLS) is a distinctive subtype
      of non-Hodgkin's lymphoma (NHL) with unique clinicopathology aspects and
      aggressive behavior. Prompt diagnosis and aggressive chemotherapy followed by
      consolidation radiotherapy may result in long-term survival in the majority of
      cases. However, a subset of patients do not respond to first-line or salvage
      treatment and have a poor prognosis. We report here a 27-year-old man with MLCLS
      resistant to several conventional chemotherapies and to radiotherapy who achieved
      a very good partial remission after one year's treatment with daily oral
      cyclophosphamide (100 mg/day). This is the first report of refractory MLCLS with
      good response to daily oral cyclophosphamide. This case suggests that daily oral
      monochemotherapy might be beneficial for some patients with mediastinal large
      cell lymphoma with sclerosis refractory to conventional intravenous
      chemotherapies and radiotherapy.

PMID- 9638991
TI  - Successful rescue in a patient with high dose methotrexate-induced nephrotoxicity
      and acute renal failure.
AB  - We describe the case of a 35-year old male who developed acute renal failure
      following high dose methotrexate therapy for Burkitt's non Hodgkin lymphoma.
      Serum methotrexate levels reached 37 micromol/l, and remained higher than 1
      micromol/l for more than a week. Folinic acid rescue was intensified to 200-400
      mg intravenously every 4 hours. As methotrexate binds markedly to proteins,
      plasma exchange was initially chosen, 4 sessions being performed from day 2 to
      day 4. The methotrexate pharmacokinetic profile was not significantly modified
      during plasma exchange, and serum drug level was 3 micromol/l. Continuous veno
      venous hemodiafiltration was therefore performed from day 5 to day 10. This
      procedure also seemed ineffective, with evidence of low ultrafiltrate clearance.
      No extrarenal toxicity was observed in our patient. Thus, conventional extrarenal
      procedures appear to have a limited role in the setting of overexposure to
      methotrexate. The use of very high doses of folinic acid in our case probably
      played a major role in the eventual favorable outcome.

PMID- 9638992
TI  - Teaching cases from the Royal Marsden Hospital. Case 16: T-cell non Hodgkin's
      lymphoma associated with hypercalcaemia in a black Caribbean.

PMID- 9638993
TI  - Nd Yag laser angioplasty: a safe procedure in peripheral vascular surgery.
AB  - BACKGROUND: Thirty-three patients (34 limbs) with peripheral vascular occlusive
      disease were treated with Nd Yag laser assisted angioplasty over a three-year
      period (1989-1991). METHODS: Sixteen males and 17 females were included in the
      study. The mean age of all patients was 70.29 (44-86) years. Twenty-two (66.7%)
      patients were smokers, 21 (63.6%) had coronary artery disease and 14 (42.4%) had
      diabetes mellitus. Thirty-three patients (100%) had disabling intermittent
      claudication, 20 patients (60.6%) had rest pain, 2 patients (6.1%) had ulcers and
      10 patients (30.3%) had gangrenous changes. Thirty-nine vessels were treated; 34
      (87.2%) superficial femoral arteries, 4 (10.3%) popliteal arteries and 1 external
      iliac artery. Eleven (28.2%) vessels were totally occluded and the remaining 28
      (71.8%) vessels had high grade stenosis of more than 90%. The mean preoperative
      ABI Index was 0.23+/-12. RESULTS: The preoperative angiogram showed poor out-flow
      in 24 (70.6%) extremities, 1 patent distal vessel in 7 extremities (20.6%) and at
      least 2 vessels in 3 extremities (8.8%). The patients were followed up for a
      period of 9.9 months (20 days-30 months). The procedure could not be done in 2
      extremities. All the remaining 32 extremities had patent vessels at the end of
      the procedure. Fifteen (48.4%) patients stated that they improved but remained
      symptomatic. Twelve (38.7%) were completely asymptomatic, 3 (9.7%) patients had
      no change in their symptoms and 2 patients worsened at the end of the follow-up
      period. The mean postoperative ABI was 0.78. Bleeding from the puncture site
      requiring closure was the most common complication of the procedure in 6 patients
      (19.4%). Angioplasty in 5 of these patients was done by the open technique. Other
      complications included hematoma in 3 (9.7%) patients and one case (3%) of artery
      perforation. Among those who remained asymptomatic at the end of the follow-up
      period the mean change in ABI was 0.625+/-0.19, those who improved but remained
      symptomatic the mean ABI change was 0.43+/-0.25 while those whose symptoms did
      not change or worsened the mean ABI change was 0.12+/-0.13. The ABI change in the
      first two groups was significantly higher than the last one (p<0.006 and p<0.001
      respectively). There was no significant difference in the outcome of LABA between
      stenosed and occluded vessels. Smoking was significantly higher in the
      symptomatic patients (7/20) compared to those who were asymptomatic 5/12, p<0.02.
      Diabetes mellitus, cardiovascular disease and the preoperative ABI were not
      significant variables in the outcome of angioplasty. CONCLUSIONS: In conclusion,
      Nd Yag laser assisted angioplasty is a safe procedure. It could relieve symptoms
      in 87.1% of cases. Change in the ABI and smoking are predictive of the success of
      the procedure.

PMID- 9638994
TI  - Occlusive disease associated with popliteal aneurysms: impact on long term graft
      patency.
AB  - OBJECTIVE: Correlate graft patency and limb salvage outcomes following popliteal
      aneurysm repair with the extent of tibial occlusive disease. EXPERIMENTAL DESIGN:
      Retrospective study with a mean follow-up of 36 months (range, 2-96 months).
      SETTING: Institutional teaching hospital. PATIENTS: Of 20 popliteal aneurysms
      among 16 patients undergoing repair, 75% were associated with preoperative tibial
      vessel occlusion. Normal, three vessel infrapopliteal runoff was present in 5
      patients, two vessels in 7 patients, and one or no vessels in 8 patients. Fifty
      percent of limbs were asymptomatic, while the remainder suffered from a variety
      of ischemic symptoms. INTERVENTIONS: Eighteen of the 20 aneurysms were repaired
      with femoropopliteal bypass grafts, and two femoral-tibial bypasses were
      performed. Autogenous saphenous vein was used in 18 cases (10 in situ, 8
      reversed) and PTFE in two short segment femoral-popliteal bypasses. MEASURES:
      Graft patency was determined by presence of a palpable pulse, the re
      establishment of normal ankle-brachial indices, or duplex scanning. Patency and
      limb salvage rates were estimated using life table analysis by the Kaplan-Meier
      method. RESULTS: Preoperative symptoms did not correlate with tibial runoff,
      except in two patients presenting with acute thrombosis and ischemia. Cumulative
      graft patency by life table analysis was not different for either good (2-3
      vessels, N-12) or poor (0-1 vessels, N-8) runoff. Overall primary patency at 60
      months was 73%, and cumulative secondary patency was 100% with no limbs lost at
      60 months. CONCLUSIONS: Concomitant distal arterial occlusive disease is
      frequently associated with popliteal aneurysms, yet did not appear to
      substantially impact either long-term graft patency or limb salvage.

PMID- 9638995
TI  - Abdominal aortic aneurysm and lower-limb occlusive arterial disease.
AB  - BACKGROUND: Abdominal aortic aneurysms (AAA) are associated with lower-limb
      occlusive arterial disease (LLOAD) in 20-40% of patients. Retrospective analysis
      of 200 elective AAA repairs and comparison with literature data revealed that
      LLOAD has little influence on standard therapeutic management of AAA. METHODS: In
      this study, only 2.5% of the patients required femoropopliteal bypass along with
      aneurysm repair. In contrast, aneurysm repair was associated with lumbar
      sympathectomy in 30% of cases owing to existence of peripheral arterial disease.
      RESULTS: Concurrent LLOAD did not significantly increase the operative mortality
      of AAA, but postoperative peripheral arterial complications were more frequent in
      patients with both aneurysmal and occlusive disease. CONCLUSIONS: Although
      concomitant LLOAD did not adversely affect the long-term survival of patients who
      underwent surgical repair of AAA, this subgroup of patients was at higher risk of
      aggravation of their lower extremity arterial lesions.

PMID- 9638996
TI  - Surgical experiences with peripheral arterial aneurysms due to vasculo-Behcet's
      disease.
AB  - BACKGROUND: Vascular involvement of Behcet's disease is currently considered as
      an important sign of the clinical evolution of patients with Behcet's disease. In
      addition, Behcet's disease is important in that it causes peripheral arterial
      aneurysms. METHODS: In this report, 4 patients with vasculo-Behcet's peripheral
      arterial aneurysms are presented. These aneurysms were distributed in the carotid
      artery (n=1), popliteal artery (n=1) and femoral arteries (n=3). Operative
      procedures included patch closure of a perforated wall for the carotid aneurysm,
      arterial reconstruction with the autogenous saphenous vein for the femoral and
      popliteal aneurysms. RESULTS: All four patients tolerated the operation well,
      however, two of four patients required re-operation due to anastomotic
      insufficiency later. CONCLUSIONS: Aneurysms associated with Behcet's disease have
      a sudden onset in many cases and often result in rupture. Appropriate operative
      procedures, including an adequate choice of anastomotic sites and reinforcement
      of the suture, may reduce the incidence of complications in patients with
      arterial aneurysms due to Behcet's disease.

PMID- 9638997
TI  - Saphenous vein sparing surgery: principles, techniques and results.
AB  - OBJECTIVE: Evaluation of saphenous vein sparing surgical procedures alternative
      to high ligation and distal stab avulsion, in terms of effectiveness and
      suitability for eventual bypass surgery. EXPERIMENTAL DESIGN: Prospective
      evaluation of 421 operations for primary varicose veins, 64 external valve
      plasties of the sapheno-femoral junction (EV-SFJ), (42 performed using the hand
      sewing technique and 22 using the Veno-cuff device), mean follow-up 52 months,
      and 357 hemodynamic correction of varicose veins (French acronymis CHIVA), mean
      follow-up 49 months. Moreover, a subgroup of 27 patients was operated on using
      the CHIVA technique in two steps, mean follow-up 18 months. SETTING: Institute of
      General Surgery, University of Ferrara. Institutional practice, one-day surgery.
      PATIENTS: Patients were selected using clinical and duplex scanning evaluations,
      and classified according to CEAP criteria. Patients with varicose veins due to
      sapheno-femoral reflux with duplex scanning evidence of mobile valve leaflets
      underwent EV-SFJ. The other patients were operated on using the hemodynamic
      correction technique. INTERVENTIONS: EV-SFJ restores valve function correcting
      vein wall dilatation by applying an external prosthesis. CHIVA consists of
      selected ligatures of the superficial veins that allow superficial blood
      aspiration in the deep veins through the perforators as well as the preservation
      of saphenous drainage. MEASURES: The outcome was evaluated with independent
      clinical and ultrasonographic examinations; pre and postoperative AVP and LRR-RT
      measurements were assessed in 125 cases. Data from self-assessment of the
      functional and cosmetic result of the patients of the CHIVA group were also
      obtained using a scoring system. Moreover, scanning the preserved long saphenous
      vein the rate of long saphenous vein suitable as arterial conduit following
      sparing surgery was also evaluated. RESULTS: Overall long saphenous vein patency
      registered after EV-SFJ and CHIVA was 94%. Varicose veins recurrence rate was 12%
      and 11%, respectively. Postoperative AVP and LRR-RT improvement was statistically
      significant (p<0.001). CONCLUSIONS: These two alternative procedures seem to be
      effective in varices treatment following the proposed indications and techniques.
      In addition, they appear able to preserve a more significant rate of saphenous
      veins suitable for eventual bypass surgery than high ligation and multiple
      cosmetic avulsion.

PMID- 9638998
TI  - Carotid string sign resulting from an aberrant branch of the internal carotid
      artery.
AB  - Branches of the extracranial internal carotid artery are very rare. A case is
      reported wherein an aberrant artery originated from the bulb of the internal
      carotid artery (ICA) approximately 2 cm from the bifurcation. The ICA was
      occluded distal to the branch's origin. Arteriography in this case gave the
      appearance of a carotid "string sign". Vascular surgeons and radiologists should
      be aware of this anomaly when interpreting carotid arteriograms.

PMID- 9638999
TI  - Traumatic pseudoaneurysm of the axillary artery following anterior dislocation of
      the shoulder. Case report.
AB  - Vascular complications are rare in cases of simple anterior dislocation of the
      shoulder but the axillary artery or its branches may be damaged. Very few cases
      are found in the literature reporting false aneurysms of axillary artery
      secondary to blunt trauma to the shoulder. A case of pseudoaneurysm of the
      axillary artery in a 75-year-old woman is reported. Diagnosis was suspected
      because large pectoral haematoma with haemodynamic instability appeared a few
      hours later after manual reduction of the dislocation. The pseudoaneurysm was
      confirmed with selective angiography of the axillary artery. Arteriography should
      be performed whenever vascular injury is suspected. Delayed recognition of these
      lesions may lead to permanent neurologic deficits despite adequate vascular
      repair of the axillary artery. A coordinated vascular and orthopaedic approach
      and prompt surgical treatment may assure full upper limb function. Although
      endovascular treatment of these lesions could seem attractive, we prefer to use
      open surgical techniques because they allow us to treat frequent concomitant
      injuries and perform decompression of the axillar fossa because of the large
      haematoma.

PMID- 9639000
TI  - Osteomyelitis of the fibula due to septic embolism: a rare complication of a
      graft enteric erosion. Case report.
AB  - We report the case of a 70-year-old female who experienced a graft enteric
      erosion (GEE) three years after a right aorto-femoral bypass. She was treated by
      right axillo-femoral bypass, removal of the aortic prosthesis and direct aortic
      suture. The duodenum was stitched up and separated from the aorta by
      omentoplasty. Bacteriological culture of the removed graft identified Escherichia
      coli and Peptostreptococcus. Antibiotic therapy consisting of Amoxicillin and
      Gentamycin was given for seven days. A month later this patient developed a
      fibula osteomyelitis due to the same germs. She was then treated by surgical
      excision of the infected tissues and by antibiotics: Amoxicillin, Metronidazole
      and Gentamycin for one month. This case of embolism into bone due to GEE is a
      rare complication which indisputably establishes a link between the spontaneously
      septic cavity of the bowel and bone tissue by way of blood via the interstices of
      the fabric. The prosthesis may be responsible for blood seeding infection and not
      only a mere victim. The prosthesis acts as a porous membrane which allows two
      opposite flows: the passage of blood from graft to bowel and germ migration from
      naturally septic bowel to blood. When a GEE is encountered, a rigorous management
      is required to prevent septic embolism. The precise timing of each step of the
      surgical procedure remains difficult to codify.

PMID- 9639001
TI  - Multivarious clinical manifestations of multiple pseudoaneurysms in Behcet's
      disease.
AB  - In Behcet's disease, an aneurysm is prone to progress rapidly to a
      pseudoaneurysm. Acute limb ischemia due to acute thrombosis of a femoral
      pseudoaneurysm and subsequent Horner's syndrome due to another subclavian
      pseudoaneurysm are very rare but acceptable complications in Behcet's disease. We
      present a case of Behcet's disease with multiple pseudoaneurysms, which also
      showed these other clinical manifestations. Over a short time span, the patient
      rapidly developed left femoral and right subclavian pseudoaneurysms, which were
      successfully resected with graft replacements.

PMID- 9639002
TI  - Dilatation of sealed Dacron vascular prostheses: a comparison of Gelseal and
      Hemashield.
AB  - OBJECTIVE: Early postoperative dilation of a gelatin-impregnated knitted dacron
      prosthesis (Gelseal, Vascutek) and a collagen-impregnated woven Dacron prosthesis
      (Hemashield, Meadox Medicals) was studied. EXPERIMENTAL DESIGN: Prospective
      study. SETTING: Institutional clinical research. MATERIALS AND METHODS: A total
      of 30 patients who underwent aortic repair for abdominal aortic aneurysm with a
      Gelseal (n=15) or Hemashield (n=15) were studied. Prior to and immediately
      following implantation, the diameter of each graft was measured with slide
      calipers. The external diameter was examined by CT scan 4 weeks after surgery.
      Early dilation of Gelseal and Hemashield was estimated and compared. RESULTS:
      Prior to implantation, the external diameter of the Gelseal and Hemashield was
      120% and 113% of the package size (PS), respectively, while the internal diameter
      was 103% and 102% of the PS, respectively. Following implantation, the external
      diameter of the Gelseal and Hemashield was 122% and 113% (immediately after) and
      129% and 118% (4 weeks later) of the PS, respectively. CONCLUSIONS: The actual
      dilation rate for the first 4 weeks after implantation was estimated as 8% with
      the Gelseal and 4% with the Hemashield.

PMID- 9639003
TI  - The effect of cardiopulmonary bypass on blood cell filterability in children
      undergoing cardiac surgery.
AB  - BACKGROUND: The extended use of cardiopulmonary bypass (CPB) in cardiac surgery
      is limited because of damage to blood which in adults has been assessed by
      alterations in blood cell rheology. Blood trauma assessment in children is
      difficult because of the restrictions in sample volume and frequency but needs to
      be established from time to time in order to study the tolerance to new surgical
      and extracorporeal techniques. MATERIALS AND METHODS: Fourteen pediatric patients
      undergoing cardiac surgery with CPB for congenital heart disease corrections were
      studied. Whole blood, red blood cell and white blood cell rheology
      (filterability) were monitored before, during and after CPB using the St. George
      filtrometer that used small amounts of blood. RESULTS: The results showed that
      all the rheologic parameters were altered during the blood trauma of CPB and were
      outside the reference values before, during and after CPB. CONCLUSIONS: This
      suggested that blood cell rheologic disturbances did not recover soon after CPB
      and this may be of interest in long term follow-up to understand responses and
      recovery patterns to disease and interventions associated with pediatric heart
      surgery using CPB.

PMID- 9639004
TI  - Papaverine solutions cause loss of viability of endothelial cells.
AB  - OBJECTIVE: The optimal composition of the solution used for irrigation of
      saphenous veins used for cardiac surgery may influence ultimate graft patency due
      to potential injurious effects on the vein endothelium of some of the solution
      constituents. EXPERIMENTAL DESIGN: The viability of cultured saphenous vein
      endothelial cells was assessed after incubation of saphenous vein endothelial
      cells with solutions containing saline, saline with papaverine (0.15 M NaCl, 32.5
      mg/mL papaverine), culture medium and buffered saline solution (Plasma-Lyte-A).
      RESULTS: Cell viability was significantly decreased after one hour incubation
      with solutions containing saline with papaverine (24.4+/-9.4%) as compared to
      culture medium and buffered saline solutions (medium 100%, Plasma-Lyte-A 86.8+/
      6.90%). Loss of viability was directly related to the length of exposure of the
      cultured cells to papaverine. Morphologic changes of cells incubated with saline:
      papaverine were also seen including cell retraction and nuclear pyknosis. The
      cells exposed to medium recovered 100% viability whereas by 4 hours only 22% of
      the saline: papaverine cells were viable, and by 3 days this viability had fallen
      to 7.7%. CONCLUSIONS: Loss of viability was shown in cultured saphenous vein
      endothelial cells exposed to saline solutions containing papaverine, whereas no
      difference was found between culture medium, saline and balanced salt solutions.
      Cell death was directly related to the length of exposure of the cells to
      papaverine. Further, after short- and long-term recovery periods, there was
      little recovery of cell viability. Although papaverine is a potent vasodilator,
      exposure to this compound may compromise long-term viability of graft endothelial
      cells.

PMID- 9639005
TI  - Incidence and risk factors of perioperative cerebral complications. Heart
      transplantation compared to coronary artery bypass grafting and valve surgery.
AB  - OBJECTIVE: The aim of this study was to define the neurologic risk of heart
      transplantation compared to coronary artery bypass grafting (CABG) and valve
      surgery. DESIGN: A retrospective study. SETTING: A university hospital. PATIENTS:
      8001 patients undergoing heart transplantation, CABG and valve surgery. MEASURES:
      The incidences of perioperative central nervous system (CNS) complications were
      compared between different procedures. Risk factors were analysed using
      univariate and multivariate methods. RESULTS: The overall incidence of CNS
      complications was 19.8% (78/393) in heart transplantation, 3.1% (176/5734) in
      elective CABG, 9.5% (161/1689) in elective valve surgery, 10.3% (15/146) in
      emergency CABG and 51.3% (20/39) in emergency valve surgery. Most powerful
      predictors of CNS complications were preoperative intra-aortic counterpulsation
      (IABP) in the heart transplantation group, age >65 years in the CABG group and
      preoperative use of catecholamine in the valve group. CONCLUSIONS: CNS
      complications occur much more frequently after heart transplantation than
      elective CABG and valve surgery. The high incidence of CNS complications after
      emergency operations as well as preoperative catecholamine and IABP as powerful
      contributing factors suggest that preoperative cerebral hypoperfusion due to a
      compromised hemodynamic state facilitates postoperative CNS complications and
      this may partly explain the high incidence of CNS complications after heart
      transplantation.

PMID- 9639006
TI  - Early and late results after surgical therapy of postinfarction left ventricular
      aneurysm.
AB  - From 1979 to 1993, 139 patients had reduction of left ventricular aneurysm (LVA)
      by plication (PL) (25 cases) linear repair (74 cases) or ventricular
      reconstruction (VR) (40 cases). Coronary bypass grafting was performed in 89
      patients. We retrospectively reviewed our experience in order to identify
      predictore of early and late outcome and determine whether ventricular
      reconstruction (VR) can improve postoperative and late prognosis. Operative
      mortality (OM) was 7.2%. Among 129 hospital survivors, 48 died during FU (LM). OM
      was related to a more recent myocardial infarction (p=0.0001), a higher residual
      score (RS) (p=0.02), a lower EF (p=0.038), a higher left ventricular score
      (p=0.059), a three-system disease (TSD) (p=0.09) and a right coronary disease
      (RCD) (p=0.13). At Multivariate Analysis (Stepwise Logistic Regression) TSD
      (p=0.001), RCD (p=0.008) and RS (p=0.04) are independent risk factors. Actuarial
      survival rate at 15 years is 33.5+/-6.9% (OM included). According to the
      comparison of the Actuarial Curves (Tests of Mantel and Breslow, OM excluded) the
      most significant risk factors were: non use of left internal mammary artery
      (LIMA) (p=0.004), VR (p=0.01), TSD (p=0.03) and higher NYHA class (p=0.019).
      Multivariate Analysis (Co Model) confirms that late prognosis is influenced by
      non use of LIMA (p=0.03) and TSD (p=0.04); outcome is also affected by
      preoperative arrhythmias (p=0.022). Five-year survival after VR is 87.5+/-5.7% vs
      64.9+/-5.5% after simple linear closure or PL (p=0.1075 and p=0.2252). Our
      results confirm that OM and LM are influenced by extent of myocardial ischemic
      damage; in agreement with the majority of Authors we advocate a complete
      revascularization using IMA, when appropriate, on left anterior descending
      artery. Our limited experience with VR fails to demonstrate this technique as an
      independent factor of late survival.

PMID- 9639007
TI  - Chylous ascites following heart transplantation.
AB  - We report a case of chylous ascites in a 52-year-old woman after an orthotopic
      heart transplantation. The patient was successfully managed with conservative
      treatment including dietetic measures and repeated paracentesis. The potential
      aetiopathological factors involved and other implications for cardiac transplant
      patients are discussed.

PMID- 9639008
TI  - Laceration of a saphenous vein graft by an epicardial pacemaker wire.
AB  - The use of temporary pacing wires has become wide-spread in cardiac surgery.
      Complications related to their use are rare. We report a case of cardiac
      tamponade following removal of an atrial pacing wire.

PMID- 9639009
TI  - Echo-guided endomyocardial biopsy in heterotopic heart transplantation. Case
      report.
AB  - Right ventricular endomyocardial biopsy is difficult to perform in patients who
      underwent heterotopic heart transplantation because of the complex vascular
      anatomy. The procedure is usually performed under fluoroscopic control. We
      present a case of a 59-year-old woman that after heterotopic heart
      transplantation underwent echo-guided endomyocardial biopsy. We report the
      technique discussing data obtained in other 11 patients heart transplanted in the
      heterotopic way. In conclusion we believe that echocardiographic guidance during
      endomyocardial biopsy allows a better choice of bite sites, reduces the risk of
      free wall perforation. Moreover is diminished the risk of X-ray exposure to both
      patient and operator.

PMID- 9639010
TI  - Myocardial abscess at a distant zone from the active valvular infection.
AB  - A case of an infective endocarditis with myocardial abscess due to Streptococcus
      anginosus at a distant location from the active valvular infection is reported.
      We conclude that local cardiac suppurative complications can appear in the
      evolution of endocarditis caused by this virulent organism.

PMID- 9639011
TI  - Bilateral thoracotomy for coronary artery bypass grafting in a patient with
      unfavorable median sternotomy.
AB  - In this report, we describe a patient who underwent coronary artery bypass
      grafting (CABG) through bilateral thoracotomy and distal median sternotomy,
      because he had received terminal tracheotomy as a treatment to prevent aspiration
      pneumonia due to Wallenberg's syndrome. On the first day after the terminal
      tracheotomy, he suddenly complained of severe anterior chest pain. Emergency
      coronary angiogram revealed complete occlusion of the proximal right coronary
      artery (RCA), severe stenosis of the left anterior descending artery (LAD) and
      the large first diagonal branch. Catheter intervention for RCA was attempted but
      it was unsuccessful, and therefore he was required to have urgent operation. The
      patient had received total laryngectomy and terminal tracheotomy two weeks before
      urgent CABG, and the large hole of the tracheotomy was just placed above the
      incisura juglaris of the sternum. So high risks of sternal infection and severe
      mediastinitis after ordinary median sternotomy were considered and we applied the
      bilateral thoracotomy approach. To our knowledge, this is very rare but effective
      approach to vascularize both right and left coronary artery and to use both left
      internal thoracic artery (LITA) and gastroepiploic artery (GEA) graft. It seemed
      that this approach is safe and effective for cardiac surgery in such situations
      that median sternotomy is not favorable as in the described patient or in
      patients having reoperation.

PMID- 9639012
TI  - Immunohistochemical properties of lipid peroxidation and prognosis in
      adenocarcinoma of the lung.
AB  - Glutathione-related enzymes are thought to influence the prognoses of patients
      with adenocarcinoma of the lung. In this study, the localization of these enzymes
      was examined immunohistochemically in the primary lesions and metastatic lymph
      nodes of 61 patients with primary adenocarcinoma. Strong immunoreactivity for
      glutathione peroxidase (GSH-PO) and superoxide dismutase (SOD) was found in
      tissue from patients with poor prognoses, while tissue from patients with
      favorable prognoses demonstrated only immunoreactivity for these enzymes.
      Therefore, believe that glutathione-related enzymes may serve as predictors of
      tumor resistance in patients with adenocarcinoma, hence measuring these enzymes
      may be useful in determining the need for adjuvant therapy.

PMID- 9639013
TI  - Lung volume reduction surgery for emphysema. A review.
AB  - Lung volume reduction surgery is emerging as a promising treatment option for
      selected patients with severe, debilitating end-stage emphysema refractory to
      medical management. Lung volume reduction surgery involves the removal of space
      occupying severely diseased, slowly ventilating and hyperexpanded lung, thus
      allowing the better conserved adjoining lung parenchyma to expand into the
      vacated space and function effectively. The operation can be accomplished by
      unilateral or bilateral thoracoscopy, thoracotomy or median sternotomy. The most
      emphysematous areas are excised using stapling or laser techniques or both. This
      review summarises the results of lung volume reduction surgery performed by
      various operative techniques. Results indicate that in the majority of patients
      improvement occurs in subjective dyspnoea and objective pulmonary function while
      oxygen and steroid dependence are reduced or eliminated at the cost of acceptable
      mortality and morbidity. Even though bilateral procedures produced much greater
      improvement, it is emphasized that it is the lung resection and not the operative
      approach that is critical to the success of the operation. Regardless of the
      technique used, the surgical treatment of emphysema is palliative in nature.

PMID- 9639014
TI  - Intraoperative cardiac tamponade complicating esophagogastrectomy.
AB  - BACKGROUND: Thoracoabdominal esophagogastrectomy is associated with a number of
      potential life-threatening complications. PATIENTS: We describe a patient with
      intraoperative hypotension in which a number of therapeutic maneuvers eventually
      led to the diagnosis of cardiac tamponade. RESULTS: Once the diagnosis of
      tamponade was made, it was successfully treated by the release of
      intrapericardial blood. CONCLUSIONS: Although rare, tamponade should be
      considered as a cause of hemodynamic instability whenever intraoperative
      manipulation of the heart has occurred.

PMID- 9639015
TI  - Rupture of the azygos vein in blunt chest trauma.
AB  - Isolated traumatic laceration of the azygos vein is a rare condition that is
      mainly associated with violent deceleration traumas. Diagnosis is crucially based
      on radiologic evidence of massive right pleural bleeding and hemorrhagic shock.
      Surgical exploration needs to be early and concomitant with resuscitation,
      prognosis largely depending on timely intervention. Median sternotomy provides
      the most advantageous access because it can be quickly performed and allows for
      surgical exploration.

PMID- 9639016
TI  - Magnetic resonance angiography in axillobifemoral grafting.

PMID- 9639017
TI  - The effect of free-radical-scavenger system "N-Acetylcysteine/Glutathione" for
      hypothermic prolonged lung cells preservation.

PMID- 9639018
TI  - Regional differences in noradrenaline-induced release of adenosine triphosphate
      from rat vascular endothelium.
AB  - We examined the release of endogenous adenyl purines such as adenosine
      triphosphate (ATP), ADP, AMP and adenosine from the caudal artery (CA), saphenous
      artery (SA), renal artery (RA), mesenteric artery (MA), pulmonary artery (PA) and
      thoracic aorta (TA) of rats, using high-performance liquid chromatography
      fluorescence detection. Noradrenaline induced the release of adenyl purines from
      these blood vessels. The total amount of adenyl purines release induced by
      noradrenaline from the CA was considerably larger than that from the TA. The rank
      order of the amount of adenyl purines released from the six blood vessels was
      CA>SA>RA>MA>PA> or =TA. The noradrenaline induced release of adenyl purines from
      the CA was significantly reduced by the removal of the endothelium. Noradrenaline
      also induced the release of adenyl purines from cultured endothelial cells of the
      CA and TA. The total amount of adenyl purines released from the former blood
      vessel was much larger than that from the latter. These results suggest the
      existence of vascular endothelial cells that are able to release ATP by an alpha1
      adrenoceptor mediated mechanism, and that these cells are not homogeneously
      distributed in the vasculature.

PMID- 9639019
TI  - Involvement of cholinergic motor neurons in pharmacological regulation of
      gastrointestinal motility by glucagon in conscious dogs.
AB  - To clarify the exact mechanisms of the pharmacological effects of glucagon on
      gastrointestinal motility, the following experiments were performed on the
      conscious and anesthetized dogs. 1) During phase I of interdigestive migrating
      contractions (IMC), glucagon (5 approximately 50 microg/kg, drip infusion for 5
      minutes) induced phasic contractions in the duodenum, jejunum and ileum, but not
      in the antrum. These excitatory responses were also observed in the truncal
      vagotomized dogs. These contractions were abolished by atropine or hexamethonium
      in the conscious dogs, and also by tetrodotoxin in the anesthetized dogs. 2)
      Glucagon inhibited cisapride-induced contractions only in the antrum in the
      conscious dogs. After pre treatment with hexamethonium, glucagon inhibited these
      contractions in the duodenum, jejunum and ileum as well as in the antrum. After
      pre treatment with tetrodotoxin in the anesthetized dogs, glucagon did not affect
      acetylcholine induced contractions in any region. 3) Glucagon inhibited
      spontaneous phase III contractions and erythromycin induced phase III like
      contractions in the antrum, but did not inhibit either contractions in the other
      regions in the conscious dogs. These paradoxical effects of glucagon between the
      antrum and intestine were similar to those involved in the blockade of 5
      hydroxytryptamine 3 receptors. After pre-treatment with hexamethonium, glucagon
      inhibited these contractions in the duodenum, jejunum and ileum as well as in the
      antrum. IN CONCLUSION: 1) Glucagon latently inhibits cholinergic motor activities
      in the antrum and intestine not directly, by binding to either receptor on the
      smooth muscle cells, but through postganglionic cholinergic neurons and possibly
      through 5-hydroxytryptamine neurons. 2) On the other hand, in the intestine the
      reverse effects through preganglionic cholinergic neurons involving nicotinic and
      muscarinic receptors are more potent. 3) As a result, glucagon inhibits antral
      contractions and does not affect intestinal contractions in a conscious state.

PMID- 9639020
TI  - Essential role of newly synthesized ATP for cyclic GMP-induced relaxation in
      alpha-toxin permeabilized smooth muscle of rat proximal colon.
AB  - The role of newly synthesized ATP in cyclic GMP-induced relaxation was studied in
      membrane permeabilized longitudinal muscle preparations of the rat proximal
      colon. Cyclic GMP and 8 bromo cGMP induced concentration-dependent relaxation of
      alpha-toxin permeabilized preparations which were precontracted by 3 microM Ca2+
      in the presence of 4 mM ATP and 5 mM phosphocreatine (PC). The relaxation by 8
      bromo cGMP was inhibited by Rp-8-pCPT cGMPS, an inhibitor of cyclic GMP dependent
      protein kinase. The relaxation was inhibited by removal of PC from the bathing
      solution, in spite of the presence of ATP. The relaxation was also inhibited by
      dinitrofluorobenzene (DNFB), a selective inhibitor of creatine kinase. The
      removal of PC or treatment with DNFB is known to produce accumulation of ADP
      within smooth muscle cell, however, ADPbetaS did not affect the relaxation. After
      irreversible inhibition of endogenous creatine kinase by DNFB in beta-escin
      permeabilized preparations, treatment of the preparations with exogenous creatine
      kinase restored the relaxation. In the presence of ADP and PC but without ATP, 8
      bromo cGMP induced the relaxation to the similar extent to that in the presence
      of ATP and PC. These results suggest that ATP newly synthesized from ADP and PC
      by creatine kinase is essential for cyclic GMP-induced relaxation of the smooth
      muscle preparations obtained from the proximal colon of rats.

PMID- 9639021
TI  - Muscarinic inhibition of L-type Ca2+ channels in guinea-pig tracheal smooth
      muscle cells.
AB  - Modulation of L-type Ca2+ channels by acetylcholine (ACh) was studied in
      enzymatically isolated guinea-pig tracheal smooth muscle cells (TSMCs). ACh
      reversibly inhibited whole cell L type Ca2+ current measured with Ba2+ ions as
      charge carriers (I(Ba)). With pipette solution containing 0.1 mM EGTA, 1 microM
      ACh induced transient inhibition of I(Ba) followed by sustained inhibition
      (67.0+/-3.7% of the control, n=19). When intracellular Ca2+ concentration
      ([Ca2+]i) was fixed at 50 nM by BAPTA-Ca2+ buffer in the pipette, the transient
      inhibition was abolished whereas the sustained inhibition (66.0+/-7.8%, n=6)
      still occurred, suggesting that the transient inhibition was attributed to
      inactivation of the channels induced by increase in [Ca2+]i. The sustained
      inhibition was abolished when [Ca2+]i was fixed at zero. The sustained inhibition
      of I(Ba) by 1 microM ACh was observed in the presence of 10 microM AF-DX 116,
      whereas it was not observed in the presence of 1 microM 4 DAMP. ACh did not
      inhibit I(Ba) in the presence of 1 mM GDP-beta-S in the pipette, whereas the drug
      irreversibly inhibited the current in the presence of 0.1 mM GTP-gamma-S in the
      pipette. Pretreatment of TSMCs with pertussis toxin did not altered the effects
      of ACh. Application of neither 1-oleoyl-2-acetyl sn-glycerol (1 microM) nor
      phorbol 12-myristate 13-acetate (1 microM) reduced I(Ba). These results suggest
      that the sustained inhibition of I(Ba) by ACh is mediated by Ca2+ requiring and
      protein kinase C-independent mechanisms existing in the downstream of G-protein
      coupled with M3 receptors.

PMID- 9639022
TI  - Pharmacological regulation of postprandial gastrointestinal motility by glucagon
      in conscious dogs.
AB  - The physiological or pharmacological role of glucagon in the postprandial
      regulation of gastrointestinal motility has not yet been clarified. To clarify
      it, the following experiments were performed on conscious dogs. Antral, duodenal,
      jejunal and ileal contractile activities were monitored by chronically implanted
      strain gauge force transducers without restraint. The serum gastrin concentration
      in response to ingestion was measured by radioimmunoassay. 1) When glucagon (5
      approximately 50 microg/kg, drip infusion for 5 minutes) was administered before
      ingestion of meal or 2 hours after ingestion, it inhibited postprandial motility
      dose-dependently in the antrum, while enhancing it in the duodenum, jejunum and
      ileum. 2) At the same time, glucagon inhibited the meal induced elevation of the
      serum gastrin concentration. 3) On the other hand, glucagon did not inhibit the
      contractions induced by pentagastrin (4 microg/kg,s.c.) or those induced by
      acetylcholine chloride (0.5 mg/kg, drip infusion for 10 minutes) in any region.
      4) These glucagon-induced inhibitory effects in postprandial antral motility were
      not affected by phentolamine (0.5 mg/kg, i.v.) or nitro-L-arginine-methyl ester
      (L-NAME) (3 mg/kg/hr, drip infusion for 30 minutes). These results suggest that:
      1) Glucagon inhibits the postprandial elevation of the serum gastrin
      concentration and thus inhibits postprandial antral motility. 2) On the other
      hand, in the intestine, glucagon-induced inhibitory responses might be reversed
      by glucagon-induced excitatory responses through preganglionic cholinergic motor
      neurons. 3) The mechanism of inhibition of gastrin release was not definite in my
      experiments, but one of the candidates may be activation of somatostatin release
      from the D cells by glucagon.

PMID- 9639023
TI  - Postprandial electrogastrographic changes with or without parasympathetic nerve
      blockade.
AB  - To investigate the relationship between postprandial electrogastrographic changes
      and parasympathetic nervous activity, 10 healthy adult males (20 to 29 years old)
      volunteered for EGG recording in the following conditions: 1) butylscopolamine
      bromide (scopolamine) administration to block parasympathetic nervous activity;
      2) after food intake; and 3) during a postprandial period after the
      parasympathetic blockade. Power spectral analysis of EGG was performed according
      to Akaike's autoregressive model. When the parasympathetic nervous activity was
      blocked, there were no changes in the dominant frequency of the EGG. During the
      postprandial period, the dominant frequency in EGG increased significantly, and
      postprandial dip (transient frequency decrease after the food intake) was
      observed in 8 of the 10 subjects. During the postprandial period after
      scopolamine administration, the dominant frequency of EGG did not increase, and
      postprandial dip was observed in only two subjects. These results suggest that
      the parasympathetic nervous activity is involved in occurrence of postprandial
      gastric motor function and postprandial electrogastrographic changes.

PMID- 9639024
TI  - Imaging of calcium release in inositol 1,4,5-trisphosphate-sensitive internal
      stores in permeabilized HSY cells using fluorescent indicators.
AB  - We described methods for imaging the IP3-induced Ca2+ release in Ca2+ storage
      organelles. IP3-induced changes in Ca2+ concentrations within Ca2+ stores
      ([Ca2+]L) in permeabilized HSY cells were monitored using the low affinity Ca2+
      indicators, mag-fura-2 and mag-fura-red. The ratio images of mag-fura-2 were used
      to estimate the [Ca2+]L in the store. The apparent [Ca2+]L was 300-1000 microM at
      the cell periphery, whereas the [Ca2+]L in the cytoplasm around the nucleus was
      70-150 microM. The [Ca2+]L throughout the cytoplasm was reduced by the
      application of 10 microM IP3 to 30-70 microM, and could be largely recovered
      after removal of IP3. The structure of IP3-sensitive Ca2+ stores was investigated
      by confocal microscopy using mag-fura-red. An IP3-induced increase in
      fluorescence was observed in the ER-like network and reticulum structures of the
      cytoplasm, and also in the nuclear envelope, suggesting that these organelles
      serve as IP3-sensitive Ca2+ stores. An analogous localization of the network and
      tubular elements of the ER was also demonstrated by electron microscopy. These
      observations suggest that these fluorescence techniques are useful to study the
      correlation between the distribution and function of Ca2+ stores.

PMID- 9639025
TI  - Localization of cytoplasmic dynein light-intermediate chain mRNA in the rat
      testis using in situ hybridization.
AB  - Expression of cytoplasmic dynein light-intermediate chain mRNA in the rat testis
      was examined using in situ hybridization. The ribonucleotide probe, referred to
      the 5' end of open reading frame (6-515 nucleotids) of cytoplasmic dynein light
      intermediate chain 53/55 (LIC-2) of the rat brain (Hughes et al., 1995. J. Cell
      Sci., 108: 17-24), was used. All spermatogenic cells were positive. Pachytene
      spermatocytes in later stages (after-stage VII) were the most intensely positive
      and round spermatids were also intense. These findings indicated that all
      spermatogenic cells may store the light-intermediate chain signal, and
      spermatocytes may produce it during later stages. The reaction in Sertoli cells
      was constant in intensity during the spermatogenic cycle, indicating that the
      light-intermediate chain mRNA signal may have no relation to the stage-dependent
      organelle transport, and that there may be post-translational regulation of the
      light-intermediate chain. In interstitium, only a few positive cells were
      observed. Northern blot hybridization demonstrated that one major band (2.0 kb)
      and two minor bands (4.4 kb and 3.5 kb) were detected in the testis, while one
      major band (4.4 kb) and one minor band (3.5 kb) were in the brain. This indicated
      that there are at least 3 isoforms in cytoplasmic dynein light-intermediate chain
      53/55.

PMID- 9639026
TI  - Immunocytochemical detection of phosphatidylinositol 3 kinase in Burkitt lymphoma
      cells.
AB  - PI 3-kinase, an enzyme responsible for the phosphorylation of the D3 position of
      the inositol ring of phosphatidylinositol (PI), is recognized to be involved in
      the regulation of many cellular processes such as mitogenic signalling,
      inhibition of apoptosis, intracellular vesicle trafficking/secretion, regulation
      of actin and integrin functions and regulation of protein kinases induced by
      tumour necrosis factor, oncoproteins and ultraviolet light. Here we report the
      subcellular distribution and the phosphorylative pattern of p85 alpha subunit of
      PI 3-kinase in Burkitt lymphoma cells exposed to R interferon alpha treatment.
      Immunocytochemical analysis of this enzyme, performed by confocal microscopy,
      revealed an increased expression of this protein at cytoplasmic level after 90
      min of interferon alpha treatment. Western blotting analyses performed on nuclear
      and cytoplasmic fractions confirmed the overexpression found by confocal
      microscopy at cytoplasmic level in the 90 min interferon alpha treated cells
      still persisting in the 24 hr treated samples. Such an overexpression was
      paralleled by an increase of tyrosine phosphorylation both at cytoplasmic and
      nuclear level suggesting that an enhanced requirement for cytoplasmic expression
      and phosphorylation of PI 3-kinase might be necessary to the cell for regulating
      some cytoplasmic-nuclear cross talk involved in the control of Burkitt lymphoma
      cell metabolism following interferon alpha treatment.

PMID- 9639027
TI  - TATA-less mouse vitronectin gene promoter: characterization of the
      transcriptional regulatory elements and a nuclear protein binding site on the
      promoter.
AB  - Vitronectin in a cell-adhesion molecule whose expression is temporally and
      spatially regulated in vivo, but whose regulatory mechanism of transcription is
      unknown. In this study, we characterized the mouse vitronectin gene promoter.
      Luciferase expression vectors cloned the successive 5'- or 3'-deletions of the 5'
      flanking region upstream of the luciferase gene and were transfected into the
      human hepatoma cell line HepG2. The assay of luciferase activity in the
      transfected cells revealed that a 38 base pair (bp)-element (positions +3 to +40)
      displays promoter activity. A consensus sequence consisting of a TATA box and
      initiator is shown around the transcription initiation site of the mouse
      vetronectin gene, but the GC box is not shown. Site-directed or deleted
      mutagenesis against a consensus sequence of TATA box and initiator could not
      abolish the promoter activity. These results induce that the putative TATA box
      and initiator are not involved in the promoter activity, and that the vitronectin
      promoter lacks the TATA box, initiator and GC box. To characterize trans-acting
      factors involved in promoter activity, a DNA fragment (position -74 to +95) was
      subjected to gel shift assay using nuclear proteins extracted from HepG2 cells.
      One shifted band was detected by the gel shift assay, suggesting that a nuclear
      protein binds to the promoter region. Results of the DNase I foot printing assay
      and gel shift assay demonstrate that the nuclear proteins can bind to the 38 bp
      element, which has promoter activity. The nuclear protein is a putative trans
      acting factor involved in transcription initiation.

PMID- 9639028
TI  - Bafilomycin A1 prevents maturation of autophagic vacuoles by inhibiting fusion
      between autophagosomes and lysosomes in rat hepatoma cell line, H-4-II-E cells.
AB  - We studied the effects of bafilomycin A1, a potent and specific inhibitor of
      vacuolar H+ ATPase (V-ATPase), on the process of autophagy in rat hepatoma cell
      line, H-4-II-E cells. To induce autophagy, cells were transferred from Dulbecco's
      modified Eagle medium containing 12% fetal calf serum into Hanks' balanced salt
      solution. When bafilomycin A1 was added to Hanks' balanced salt solution,
      endogenous protein degradation was strongly inhibited and numerous autophagosomes
      accumulated in H-4-II-E cells, whereas autolysosomes decreased in number. Acid
      phosphatase activity was not detected in the autophagosomes which accumulated in
      the presence of bafilomycin A1, suggesting that fusion between autophagosomes and
      lysosomes was disturbed by this drug. Inhibition of the fusion was reversible,
      and the autophagosomes changed into autolysosomes after the removal of the
      inhibitor. Bafilomycin A1 also prevented the appearance of endocytosed HRP in
      autophagic vacuoles. These results suggested that acidification of the lumenal
      space of autophagosomes or lysosomes by V-ATPase is important for the fusion
      between autophagosomes and lysosomes.

PMID- 9639029
TI  - Structural analysis of milk and testis beta-1,4-galactosyltransferase gene
      products.
AB  - There seems to exist a relatively low similarity between the amino acid sequences
      of the testis and milk beta-1,4-galactosyltransferase gene products. However, the
      predicted higher structures of testis and milk beta-1,4-galactosyltransferase
      proteins revealed a highly significant similarity in the regions required for
      enzymatic activities. Testis beta-1,4-galactosyltransferase protein contained a
      WD repeat similar to the motif of the G protein beta subunit type I and a Zn
      finger motif at the N- and C-terminal portions of the protein, respectively.
      Phylogenetic analysis of glycosyltransferase proteins revealed that the ancestral
      gene of testis and milk beta-1,4-galactosyltransferases and alpha-1,3
      galactosyltransferase evolved into three different destinations at about the same
      time on an evolutionary scale.

PMID- 9639030
TI  - A stereotaxic atlas of the grey lesser mouse lemur brain (Microcebus murinus).
AB  - In response to the growing interest in the prosimian Microcebus murinus for
      studies on cerebral aging, the stereotaxic atlas of its brain was carried out in
      view of further anatomical, biochemical, electrophysiological, and behavioral
      investigations as well as for therapeutic experiments. This primate, which could
      be a valuable model for neuroscientific studies in various domains, presents
      numerous physiological advantages (e.g., size, cost, and ability to breed)
      compared to rodents, which can be used as nonprimate models, and simians. The
      atlas, valid for adult microcebes of every age and both sexes, consists of 54
      frontal plates and 28 sagittal plates. For the establishment of stereotaxic
      coordinates and for drawings and photographs, 10 adult specimens of Microcebus
      murinus were used. The brains were frozen, cut into sections of 50 microm
      thickness, every fourth section being stained with Nissl. First, sections were
      projected and the outlines of the different structures, nuclei, and fibers were
      drawn. Then, the accuracy of the analysis was improved by detailed observation
      directly by microscope and also by computer analysis. Finally, the photographs of
      the sections were scanned and processed using the software Photoshop and
      Illustrator. For testing coordinates, several verifications were made.
      Experiments on lesions and injections of different substances were carried out in
      specific regions of the brain and brains implanted with needles were fixed in
      formol and embedded in paraffin wax.

PMID- 9639031
TI  - The calcium receptor in health and disease.
AB  - The recent cloning of a G-protein-coupled, extracellular calcium [(Ca2+)e]
      sensing receptor (CaRG) from the parathyroid, kidney and brain of several species
      has clarified the molecular mechanisms underlying Ca2+-sensing by parathyroid and
      other cell types. It has long been suspected that such a receptor existed on
      parathyroid cells, coupled to intracellular second messengers through guanine
      nucleotide regulatory (G) protein which is able to recognize and respond to
      (Ca2+)e. Recently, functional screening of a cDNA library constructed from bovine
      parathyroid mRNA led to the isolation of a 5.3-kb clone expressing maximal Ca2+
      stimulated Cl- currents in oocytes. This 5.3-kb cDNA encodes a protein of 1,085
      amino acids with three principal predicted structural domains. The CaRG protein
      is present in chief parathyroid cells, in C cells of the thyroid, in the cortical
      thick ascending limb (TAL) and collecting duct of the kidney, and in discrete
      brain areas. CaRG may play several physiological roles. It is a central element
      in the control of both parathyroid and calcitonin secretion by (Ca2+)e. Moreover,
      functional evidence for its participation in the regulation of renal Ca2+
      reabsorption in TAL and water reabsorption in the collecting duct has been
      obtained. Mutations of the CaRG gene are responsible for hereditary and familial
      parathyroid disorders, and a decrease in CaRG expression has been documented in
      primary and secondary uremic hyperparathyroidism. The expression of CaRG in
      several additional organs and tissues allows speculation on the potential
      involvement in other pathologies.

PMID- 9639032
TI  - Prostaglandin receptors in the kidney: a new route for intervention?
AB  - Prostaglandins comprise a structurally diverse family of cyclooxygenase
      metabolites of arachidonic acid, including thromboxane A2, PGD2, PGE2, PGF2alpha
      and PGI2. These prostaglandins are now known to act via different G-protein
      coupled receptors. PGE2, the major prostaglandin synthesized along the nephron,
      interacts with at least four E-prostanoid (EP) receptors, three of which are
      highly expressed in distinct regions of the kidney. Each EP receptor also
      preferentially couples to a different signal transduction pathway, including
      stimulation of cAMP generation by the EP2 and EP4 receptors; inhibition of cAMP
      generation, via Gi by EP3 receptors, and activation of phosphatidylinositol
      hydrolysis by EP1 receptor. Other intrarenal prostanoid receptors include the
      thromboxane A2 receptor and the prostacyclin receptor. These receptors also
      exhibit a discrete intrarenal distribution. The possibility of pharmacologically
      targeting each renal prostanoid receptor may provide a unique approach to
      modifying renal function in disease states.

PMID- 9639033
TI  - Adeno-associated virus gene transfer into renal cells: potential for in vivo gene
      delivery.
AB  - The human parvovirus adeno-associated virus (AAV), type 2, has a number of
      features that make it an attractive choice as a vector for gene delivery to the
      kidney. AAV vectors permit long-term gene expression in vivo by integration into
      the host genome, have potential for site-specific integration on chromosome 19,
      do not express viral genes or generate a cellular immune response, and
      demonstrate enhancement of gene expression by chemotherapeutic agents that are
      approved for use in vivo. These properties confer advantages to AAV over other
      viral and nonviral methods for gene transfer. Preliminary experiments in our
      laboratory suggest that AAV is able to transfer genes to both renal cells in
      culture and the kidney in vivo. Thus, AAV has the potential to be an important
      gene transfer vector for the kidney in vivo.

PMID- 9639034
TI  - Endogenous inhibitors of nitric oxide synthesis: how important are they?
AB  - In animals and humans, inhibition of nitric oxide (NO) production has widespread
      effects. Reduced activity of the NO:cyclic GMP pathway has been documented in
      disease states, including hypertension, diabetes and certain types of renal
      disease. Inhibitors of NO synthesis occur endogenously, and have been implicated
      in the regulation of the NO pathway in health and disease. Here we review the
      possible biological roles of endogenous NO synthase inhibitors, with particular
      reference to renal disease.

PMID- 9639035
TI  - Potential functional roles of extracellular ATP in kidney and urinary tract.
AB  - P2 receptors are sensitive to adenosine triphosphate (ATP) and uridine
      triphosphate and can be divided into two major subtypes: P2X and P2Y receptors.
      They are specific membrane-bound receptors which when activated by extracellular
      ATP initiate a variety of biological effects. The P2X receptors are ligand-gated
      channels, whereas the P2Y receptors are coupled to G proteins linked to second
      messenger systems. In this review, the potential functional roles of
      extracellular ATP in the kidney and lower urinary tract are discussed and briefly
      explored in the context of some specific renal and urinary tract abnormalities.

PMID- 9639036
TI  - Production of inflammatory mediators and cytokine responsiveness of an SV40
      transformed human proximal tubular epithelial cell line.
AB  - Proximal tubular epithelial cells (PTEC) play a central role in the physiology of
      the renal tubulointerstitium. To be able to study the relationship between
      tubular cells and inflammatory renal diseases the availability of cultured cells
      is of importance. This study describes an immortalized proximal tubular
      epithelial cell line which was generated using SV40 DNA. To determine whether the
      transformation altered the cell line, the transformed cell line was characterized
      phenotypically using different monoclonal antibodies directed against peptidases,
      which are characteristic of PTEC, such as adenosine deaminase binding protein
      (CD26), leucine amino peptidase and carboxy peptidase M by immunofluorescent
      staining and FACS analysis. All peptidases were clearly present on the parental
      cell line and the transformed cell line. However, the level of expression of the
      peptidases was lower on the transformed cell line as compared to the parental
      nontransfected cells. The morphology of the transformed cell line, determined
      using a transwell culture system and electron microscopy, showed a polarized
      morphology of the tubular cells, tight junctions and microvilli. The transformed
      cell line was compared with the parental proximal tubular epithelial cells in its
      ability to respond to inflammatory cytokines such as IL- 1alpha TNF-alpha, IFN
      gamma. Stimulation with these cytokines resulted in enhanced production of
      complement components C2, C3, C4 and factor H, IL-6 and the chemokines IL-8 and
      MCP-1. The transformed cell line responded in a similar fashion as the parental
      cell line, although the amount of the different proteins produced was
      significantly higher in the transformed cell line. Overall, the transformed
      tubular cell line seems to be a suitable model to study different effects on
      tubular cells in relation to inflammatory kidney diseases.

PMID- 9639037
TI  - Expression of cytoskeletal proteins differentiates between progressors and non
      progressors in treated idiopathic membranous nephropathy.
AB  - Myofibroblasts play an important role in wound healing in a variety of tissue
      injuries. They have also been implicated in tissue fibrosis including renal
      scarring. This study was aimed at defining their role in one of the commonest
      forms of nephrotic syndrome in adults, namely membranous nephropathy. We have
      studied 21 patients with biopsy proven idiopathic membranous nephropathy who were
      treated with glucocorticoids, attempting to define the role of myofibroblasts
      (alpha-smooth muscle actin-positive as well as vimentin-positive cells) in the
      progression of this form of nephropathy. There were 13 non-progressors (NP) and 8
      progressors (P). The clinical, histological, and immunohistochemical
      characteristics of both groups were compared. Immunohistochemical staining for
      myofibroblasts cytoplasmic markers a-smooth muscle actin (alpha-SMA) and vimentin
      relied on an avidin-biotin-peroxidase method. The level of blood pressure, degree
      of proteinuria, severity of interstitial infiltrate and interstitial fibrosis did
      not differentiate P from NP. However, vascular sclerosis was more severe in P
      compared to NP (p < 0.016) and its severity predicted the subsequent functional
      outcome (slope of the 1/serum creatinine against time; r2 = 0.618, p < 0.01).
      Mesangial alpha-SMA was significantly higher in P (31 +/- 18.6%) than in NP (14.5
      +/- 9.8%), p < 0.015. Interstitial alpha-SMA immunostain was also higher in P but
      did not reach statistical significance. However, the number of interstitial
      myofibroblasts (alpha-SMA positive cells) closely predicted the subsequent rate
      of the progression of chronic renal failure (r2 = 0.919, p < 0.0001). Mesangial
      vimentin expression was not different between both groups. By contrast,
      interstitial vimentin immunostain was higher in P (19.1 +/- 8.8%) compared to NP
      (7.9+/-5.6 %), p < 0.002. These data suggest that the expression of mesangial and
      interstitial cytoskeletal proteins (alpha-SMA and vimentin) may have useful
      prognostic implications as they appear to differentiate between patients with
      membranous nephropathy who respond to immunosuppression and those who continue to
      progress.

PMID- 9639038
TI  - The renal TGF-beta system in the db/db mouse model of diabetic nephropathy.
AB  - The prosclerotic cytokine transforming growth factor beta 1 (TGF-beta1) has been
      causally implicated in renal pathobiology in diabetes. We sought evidence that
      the TGF-beta system participates in the nephropathic process in the db/db mouse,
      a hyperinsulinemic model of genetic diabetes that develops abnormalities in renal
      morphology and function that parallel those in human diabetic nephropathy. In
      support of this hypothesis, we found that steady state levels of mRNA encoding
      the TGF-beta type II receptor were significantly increased in renal cortex from
      db/db diabetic mice. Additionally, the translated TGF-beta type II receptor
      protein, assessed by immunoblot, also was increased in diabetic kidneys. However,
      in contrast to rodents with insulin-deficient diabetes, steady state levels of
      mRNA encoding TGF-beta1 in the renal cortex of diabetic db/db mice did not differ
      from those in cortex from nondiabetic (db/m) littermate controls. Further,
      concentrations of TGF-beta protein, measured by immunoassay and bioassay, were
      significantly lower in extracts prepared from renal cortex of diabetic animals
      compared with those from nondiabetic controls. Urine and serum concentrations of
      immunoreactive TGF-beta1 also were reduced in diabetic mice. The findings are
      consistent with upregulation of TGF-beta type II receptor activity as a
      consequence of hyperglycemia in the hyperinsulinemic db/db mouse and suggest that
      hyperinsulinemia inhibits TGF-beta1 production. The results further suggest that
      type II receptor upregulation is a contributing factor to the increased gene
      expression of renal cortical mRNAs encoding the extracellular matrix proteins
      fibronectin and alpha 1 (IV) collagen and to the renal abnormalities observed in
      this animal model.

PMID- 9639039
TI  - Podocyte phenotypes as defined by expression and distribution of GLEPP1 in the
      developing glomerulus and in nephrotic glomeruli from MCD, CNF, and FSGS. A
      dedifferentiation hypothesis for the nephrotic syndrome.
AB  - Glomerular epithelial protein 1 (GLEPP1) is a podocyte receptor membrane protein
      tyrosine phosphatase located on the apical cell membrane of visceral glomerular
      epithelial cell (VGEC) foot processes. Double label immunofluorescence,
      immunoelectron microscopy, and peroxidase immunohistochemistry were used to map
      the GLEPP1 distribution in the developing glomerulus and in minimal-change
      nephropathy (MCN), congenital nephrotic syndrome of the Finnish type, and focal
      segmental glomerulosclerosis (FSGS). In MCN GLEPP1 was shifted away from the
      glomerular basement membrane on the apical cell membrane of effaced foot
      processes. These data are compatible with the previously suggested concept that
      MCN can be considered a form of dedifferentiation of the podocyte phenotype.
      Similarly, changes seen in congenital nephrotic syndrome of the Finnish type can
      be considered a consequence of failure to complete normal podocyte development.
      In FSGS glomeruli GLEPP1 was frequently absent from VGECs, even when no sclerosis
      was detectable in that glomerulus. Therefore, in FSGS, VGECs may lose GLEPP1, and
      this loss appears to occur in the absence of scarring and may, therefore, precede
      the scarring process. We speculate that a changed VGEC phenotype that does not
      express GLEPP1 might have properties similar to the early undifferentiated VGEC
      developmental phenotype. GLEPP1 distribution pattern and absence from glomeruli
      of individuals with nephrotic syndrome may, therefore, represent a useful
      phenotypic marker.

PMID- 9639040
TI  - Renal hemodynamic response to erythropoietin-induced polycythemia in 5/6
      nephrectomised rats is different from normal rats.
AB  - The effects of recombinant human erythropoietin (rHuEPO)-induced polycythemia on
      renal function and glomerular hemodynamics were evaluated in Munich-Wistar rats
      (MW+EPO) before and after infusion of indomethacin; the rHuEPO effects on total
      renal function were also evaluated in 5/6 nephrectomized (CRF) MW and
      spontaneously hypertensive rats (MW-CRF+EPO and SHR-CRF+EPO, respectively). In
      normal MW rats, rHuEPO (300 IU/kg BW, 3 x /week, during 2 weeks) induced
      elevation in MAP, with maintenance of GFR, paralleled by superficial
      vasodilatation and elevation in SNGFR, suggesting cortical blood redistribution.
      These hemodynamic alterations induced by rHuEPO were blunted by indomethacin,
      suggesting a participation of the vasodilator prostaglandins in the renal
      compensatory mechanism of polycythemia. Elevation in MAP and reduction in GFR
      occurred in the MW-CRF+EPO group compared with the group receiving vehicle. In
      contrast, the SHR-CRF+EPO presented a reduction in MAP and maintenance of GFR,
      suggesting different rHuEPO effects depending on previous renal function and/or
      hypertensive state.

PMID- 9639041
TI  - Expression of Id-1 mRNA and protein in the post-ischemic regenerating rat kidney.
AB  - The basic helix-loop-helix (bHLH) class of proteins are of major importance in
      controlling tissue-specific gene expression. The actions of the bHLH proteins are
      inhibited by a related class of proteins, inhibitors of differentiation (Id). We
      have studied the expression of one of these latter proteins, Id-1, in the normal
      and post-ischemic regenerating rat kidney by immunocytochemistry, Western blot
      and RNase protection assay (RPA) and correlated Id-1 regulation to the expression
      of vimentin and proliferating cellular nuclear antigen (PCNA). In the normal
      kidney strong immunostaining for Id-1 was found in the distal nephron, especially
      in the distal convoluted tubule in the cortex. In particular, the perinuclear
      region was intensely stained in the cells of the distal tubule. mRNA for Id-1I
      was detectable by RPA on total RNA extracted from the renal cortex of sham
      operated animals. The Id-1 monomer was detected on Western blots of normal
      animals. Vimentin was expressed in the mesangial cells of the glomeruli and in
      cells in the interstitium while tubule cells were negative. The labeling
      intensity for PCNA was low in all cellular compartments in the normal kidney. In
      the regenerating kidneys at various time intervals, the expression of Id-1-like
      immunoreactivity was widespread in the regenerating dedifferentiated tubule cells
      while by the end of the study period, more highly differentiated tubule cells
      appeared to lose their staining. On Western blots the Id-1 monomer was
      undetectable and instead strong staining was seen in the high molecular range. Id
      1 mRNA levels in the regenerating kidneys did not differ significantly when
      compared to sham. PCNA labeling was intense in the regenerating kidneys at all
      time periods studied, indicating the intense proliferative activity in the
      regenerating kidneys. Vimentin expression in the renal tubule cells was increased
      from day 3 and onward. The data are consistent with a hypothesis in which Id-1
      regulates differentiation of renal tubule cells in the post-ischemic regenerating
      rat kidney.

PMID- 9639042
TI  - Y-chromosome deletions and male infertility: state of the art and clinical
      implications.

PMID- 9639043
TI  - The acid-fast stain is a superior stain for use in the mean mature spermatid
      count for testicular biopsies.
AB  - The mean mature spermatid count (MMSC) provides a useful, simplified quantitative
      evaluation of human spermatogenesis that is based on the number of mature
      spermatids in histological sections of testicular biopsies. Here, the activity of
      the acid-fast (AF) stain was compared to that of the usual hematoxylin and eosin
      (H&E) stain in performing the MMSC. Thirty bilateral testicular biopsies showing
      normal spermatogenesis were chosen retrospectively from 15 subfertile patients
      with obstructive azoospermia or severe oligospermia. The MMSC was determined on
      each biopsy by utilizing both H&E and AF stains. The AF stain proved to be
      specific for the mature spermatids normally counted for the MMSC. It simplified
      recognition of mature spermatids, thereby shortening the overall time required
      for the procedure. The mean AF MMSC was lower than the mean H&E MMSC, and the
      mean interobserver differences were decreased. The AF stain is a superior stain
      for the MMSC when used in conjunction with the H&E stain for descriptive
      histology.

PMID- 9639044
TI  - Vitamin E deficiency causes incomplete spermatogenesis and affects the structural
      differentiation of epithelial cells of the epididymis in the rat.
AB  - The effects of vitamin E deficiency on the rat testis and epididymis were
      examined in a light- and electron-microscopic analysis. Various groups of animals
      were made vitamin E-deficient, beginning at postnatal day 10, via their lactating
      mothers, until day 21, when they were separated from their mothers. The groups
      were maintained thereafter on either a vitamin E-deficient or a normal diet
      (controls). The vitamin E-deficient animals of group A, sacrificed at day 42,
      revealed testes that were normal in appearance, with a full complement of germ
      cells when compared to their controls (group B). Group C, however, sacrificed at
      day 48, revealed major abnormalities in the testes, unlike both their controls
      (group D) and normal, untreated animals (group E). Spermatogenesis was
      incomplete; the most advanced cell type was predominantly step-7 spermatids.
      However, many of these cells, as well as earlier spermatids, appeared to undergo
      degeneration, evidenced by large pale areas in their nuclei, disrupted acrosomes,
      and a cytoplasm with uncharacteristic organelles. Multinucleated cells,
      characterized by their chromatoid bodies as spermatids, were often seen in the
      seminiferous tubule lumen. Sertoli cells were normal in appearance, except for
      numerous, large lipid droplets in their basal region, at stages I-VIII; in
      appropriate controls (group D), such droplets were absent at these stages. These
      lipid inclusions presumably represented the final breakdown products of the late
      spermatids, which were phagocytosed by Sertoli cells between days 42 and 48.
      However, numerous germ cells, often recognized as round spermatids, and
      multinucleated cells were noted in the epididymal lumen, which indicates that
      such cells were spared from Sertoli cell phagocytosis. These data suggest that
      vitamin E plays a key role in the maintenance and survival of spermatids. In the
      epididymis, vitamin E deficiency resulted in principal, narrow, and apical cells
      that showed a poorly developed secretory and endocytic apparatus at days 42
      (group A) and 48 (group C), unlike those of normal, untreated animals (group E).
      On the other hand, clear cells of groups A and C showed a highly developed
      endocytic apparatus in the cauda region only, whereas in the caput and corpus
      regions, endocytic apparatuses were small and undifferentiated, unlike those of
      group E. Thus, in the epididymis, vitamin E plays a role in the structural
      differentiation of principal cells along the entire epididymis, whereas, in the
      case of clear cells, its role is region-specific. Readministration of vitamin E
      to the diet restored a normal appearance to both the testis and the epididymis,
      which indicates that the effects on these tissues are reversible. Taken together,
      these data indicate that vitamin E plays important roles in maintaining the
      viability of the spermatid population and in allowing epithelial epididymal cells
      to acquire their fully differentiated structural appearance.

PMID- 9639045
TI  - Activation of coagulation factor X in human semen.
AB  - Tissue factor (TF) is an essential cofactor for factor VII (fVII) in initiating
      blood coagulation. Recently, TF was shown to be present in human semen and to be
      associated with prostasomes that originate from prostatic secretions. In the
      blood coagulation cascade, the complex of TF and activated factor VII (fVIIa) can
      activate both factor X and factor IX, by limited proteolysis. In the present
      study, we investigated the ability of semen to activate factor X. We also
      determined that factor X was activated predominantly by TF-fVIIa and that most of
      the TF was present in the seminal plasma, consistent with prostasome
      localization. No endogenous factor X was detected in semen, but activation of
      added factor X occurred in the absence of added fVIIa. Subsequent experiments
      showed that seminal plasma contains endogenous fVII-like activity, but the
      addition of more fVIIa increased factor X activation. Thus, while seminal plasma
      contains significant amounts of TF, its potential to activate factor X is limited
      by fVII availability and by the absence of endogenous factor X. Evaluation of
      semen specimens from infertility patients revealed a 16-fold variation in TF-fVII
      activity. No relationship between TF and number of days of abstinence, specimen
      pH, sperm count, or sperm motility was evident. Additional factor X-activating
      potential, independent of further TF activity, was generated in seminal plasma
      after treatment of semen with calcium and ionophore A23187. Production of this
      additional activity was blocked by the addition of anti-TF antibody during the
      activation. Since there is no factor X endogenous to semen, the additional
      activity stimulated by A23187 appears to be due to an endogenous, non-factor X
      substrate for TF-fVII in semen. This endogenous substrate may be either factor IX
      or a novel new substrate for TF-fVIIa. Future experiments will test these
      hypotheses.

PMID- 9639046
TI  - Semen donor selection by in vitro sperm mobility increases fertility and semen
      storage in the turkey hen.
AB  - Commercial turkey production relies on the artificial insemination (AI) of pooled
      semen. However, semen quality ultimately depends on the quality of individual
      ejaculates. The purpose of this study was to evaluate semen from individual toms
      by means of an objective sperm-mobility assay. Semen was then pooled by mobility
      phenotype and inseminated into hens, and the percentages of fertile and hatched
      eggs were determined after egg incubation. To indirectly evaluate hens' sperm
      storage, we determined the number of sperm holes in the perivitelline layer (PL)
      of freshly laid eggs. Semen from individual ejaculates (two trials, total of 169
      toms) was evaluated by use of the sperm-mobility test (SMT). Semen was diluted to
      1 x 10(9) sperm/ml, in prewarmed N-tris-[hydroxymethyl] methyl-2-amino
      ethanesulfonic acid (TES)-buffered saline, and was placed over 3 ml of a 2% (w/v)
      Accudenz solution at 41degrees C. After a 5-minute incubation period, the cuvette
      was placed in a densimeter, and percentage transmission was recorded after 1
      minute. Semen samples from toms ranked, according to sperm mobility, in the
      highest 10% and the lowest 10%, after three evaluations, were pooled by group and
      were used to inseminate hens weekly (trial 1: n = 20 hens/group, for 10 weeks, AI
      dose 150 x 10(6) spermatozoa inseminated fresh and after 24-hour in vitro storage
      at 5 degrees C; trial 2: n = 60 hens/group, for 16 weeks, AI dose = 75 x 10(6)
      spermatozoa inseminated fresh). Each week, eggs from day 6 post-AI were evaluated
      for holes in the PL, vestiges of acrosomal induced hydrolysis. Spermatozoa from
      toms of different mobility phenotypes were also evaluated individually, for sperm
      chromatin structure and motility variables, by use of the Hobson Sperm Tracker.
      Toms characterized by high and low in vitro sperm-mobility phenotype were
      categorized as "high mobility" and "low mobility," respectively. The percentage
      of fertile eggs from hens inseminated with semen from the high-mobility toms was
      higher than the percentage of fertile eggs from the low-mobility group, in each
      trial (95.8+/-1.3% vs. 90.4+/-2.2%, and 88.7+/-4.0% vs. 82.4+/-0.4%, trials 1 and
      2, respectively; P < 0.05). More sperm holes were observed in the PL of eggs
      fertilized by the high-mobility toms than in the PL of eggs fertilized by the low
      mobility toms (P < 0.05). No differences in susceptibility of sperm nuclear DNA
      to denature in situ, as measured by the flow-cytometric sperm chromatin-structure
      assay, were detected between toms of differing mobility phenotypes. Sperm
      motility variables, straight-line velocity, and average-path velocity were
      significantly greater for high-mobility toms compared to low-mobility toms (P <
      0.05). Sperm-mobility differences between toms (detected by means of the SMT)
      influenced sperm storage, as indicated by the number of sperm in the PL and by
      the percentage of fertile eggs produced.

PMID- 9639047
TI  - Presence and modulation of interleukin-12 in seminal plasma of fertile and
      infertile men.
AB  - Interleukin-12 (IL-12) is a unique cytokine that recently has drawn considerable
      attention because of its immunomodulatory properties and its possible involvement
      in several normal physiological and pathophysiological processes. In the present
      study, concentrations of IL-12 were determined, in the seminal plasma of fertile
      (n = 33), male-factor-infertile (n = 27), and immunoinfertile (n = 14) men, to
      investigate its role, if any, in male infertility. Levels of IL-12 were expressed
      both as picograms per milliliter and as picograms per milligram protein. IL-12
      was detected in seminal plasma of fertile men as well as in that of infertile
      men. The levels of IL-12 in seminal plasma of both male-factor and
      immunoinfertile men were significantly (P < 0.05) different from those of fertile
      men, when levels were expressed as picograms per milligram protein. When
      expressed as picograms per milliliter, the levels of IL-12 differed significantly
      between the immunoinfertile group and the fertile/male-factor-infertile group.
      There was significant correlation between the IL-12 levels and the total sperm
      count and percentage of morphologically normal sperm in the semen, whether groups
      were analyzed together or individually by condition. These findings suggest that
      IL-12 may have a role in fertility and that its derangement may be involved in
      male infertility.

PMID- 9639048
TI  - Hormonal regulation of spermatogenesis in the hypophysectomized rat: FSH
      maintenance of cellular viability during pubertal spermatogenesis.
AB  - The potential for follicle-stimulating hormone (FSH) to promote germ-cell
      survival and the cellular sites of FSH action were studied using a gonadally
      maturing (pubertal), hypophysectomized (Hx) rat model in which residual
      testosterone (T) activity was blocked by injections of an androgen-receptor
      antagonist, flutamide. Recombinant human FSH was given to androgen-deprived and
      androgen-blocked male rats at 27 days of age to determine maintenance of
      individual germ-cell types at 35 days of age. Follicle-stimulating hormone
      significantly increased testis weights and tubular diameters as compared with Hx
      and Hx-flutamide controls, although testis weights in FSH-treated animals were
      significantly lower than in pituitary-intact animals. Morphometric assays to
      determine ratios of germ cells to Sertoli cells and to determine the number of
      germ cells present per hour of development showed that the population of type A
      spermatogonia in the early stages of the cycle was not responsive to FSH.
      Follicle-stimulating hormone had a marked ability to maintain cell viability in
      the rapid, successive divisions that begin in the latter part of the cycle and
      that continue through the next cycle (i.e., from type A1 to A4 and from
      intermediate spermatogonia to type B spermatogonia to preleptotene spermatocytes
      to leptotene/zygotene spermatocytes to young pachytene spermatocytes). The data
      also suggest T responsiveness of these cell types since the Hx-FSH-flutamide
      group showed lower cell viability at the aforementioned steps when compared with
      the Hx-FSH group. Too few cell types were present at subsequent phases of
      spermatogenesis to allow a sensitive determination of FSH activity in the
      maintenance of cell viability. The data show the potential of FSH in the absence
      or relative absence of T activity to maintain cell viability. These data support
      the concept of overlapping and synergistic (or additive) effects of T and FSH in
      the immature rat and identify the cellular sites of FSH action.

PMID- 9639049
TI  - Hormonal regulation of spermatogenesis in the hypophysectomized rat: cell
      viability after hormonal replacement in adults after intermediate periods of
      hypophysectomy.
AB  - A quantitative analysis of germ-cell populations in normal, hypophysectomized
      (Hx), and Hx-hormone-treated animals was undertaken during periods of regression
      that were characterized as intermediate, between short-term and long-term
      regression of the testis. Twenty-one groups of adult rats were administered
      either follicle-stimulating hormone (FSH), growth hormone, thyroid-stimulating
      hormone (TSH), or testosterone (T) in various doses and combinations. The dosage
      of T administered was less than that expected to achieve maximum testis weight.
      Flutamide and Casodex were used to compete with androgen binding to receptors in
      Hx animals, as it is known that small amounts of androgen are secreted in the
      absence of pituitary stimulation. Follicle-stimulating hormone, T, and TSH all
      significantly maintained testis weight as compared with Hx controls, although FSH
      and T, singly or in combination, were the most effective. Contamination of the
      TSH preparation with trace amounts of FSH was apparently responsible for the
      slight maintenance of testis weight. A novel assay for determination of the
      numbers of viable germ cells was used in a subset of these groups to determine
      the cellular sites of FSH and T action. Numbers of type A spermatogonia were
      lowered after Hx and were maintained by either FSH or T or a combination of these
      hormones. Other phases of germ-cell development most susceptible to FSH and/or T
      were the successive conversions of type A spermatogonia to intermediate
      spermatogonia, intermediate spermatogonia to type B spermatogonia, preleptotene
      spermatocytes to pachytene spermatocytes, and early pachytene spermatocytes to
      intermediate maturity pachytene spermatocytes during early and midcycle phases of
      pachytene spermatocyte development. Germ-cell loss during meiosis and virtually
      every phase of spermatid development was largely prevented by FSH or T or a
      combination of these hormones. Thus, in testes in advanced stages of regression,
      both FSH and T were capable of preventing cell loss, suggesting that both
      hormones can affect the survival of the same cell type. The present study
      demonstrated that FSH can partially compensate for lowered T levels. The combined
      administration of FSH and T was more effective in preventing overall cell
      degeneration than either hormone alone. Unlike the initial phase of
      spermatogenesis, in which there is a largely midcycle loss of germ cells due to
      Hx, the loss of cells during testis regression is more widespread and impacts
      several cell types in more than one stage of the spermatogenic cycle.

PMID- 9639050
TI  - Hormonal regulation of spermatogenesis in the hypophysectomized rat: quantitation
      of germ-cell population and effect of elimination of residual testosterone after
      long-term hypophysectomy.
AB  - Spermatogenesis continues after long-term hypophysectomy (Hx), but massive cell
      degeneration prevents seminiferous tubules from attaining the full complement of
      cells. One objective of this study was to determine the vulnerable sites for
      completion of spermatogenesis in long-term Hx rats. It is now known that Leydig
      cells continue to secrete small amounts of androgen after Hx. A second objective
      was to determine the cellular sites that are maintained by residual androgen
      secreted by Leydig cells post-Hx. Two groups of adult animals were utilized. Both
      groups were Hx for 36 days, but one group of rats received the androgen
      antagonist flutamide during the 26th through the 36th day of Hx (10 days). Germ
      cell numbers were quantified using a method that allowed their expression as
      numbers of cells present per hour of development. In the long-term Hx rat, the
      germ-cell population increased to preleptotene, but the divisions that led to
      preleptotene were inefficient due to cell degeneration. Subsequent to
      preleptotene, there was a gradual loss in cells such that there were few germ
      cells remaining by steps 9-13. Flutamide given to Hx rats did not result in a
      significant difference in the numbers of intermediate and type B spermatogonia or
      significant differences in progenitor cells. A significant and major depression
      of cell numbers in Hx-flutamide-treated rats occurred in the cell division of
      type B spermatogonia to form preleptotene spermatocytes. There was a less
      dramatic, although significant, depression of cell numbers in Hx-flutamide
      treated animals that occurred from preleptotene until late pachytene as well as
      an increased loss of round spermatids at midcycle (step 5-6). These data
      demonstrate that cell loss after long-term Hx occurs at numerous phases of
      spermatogenesis. The data also demonstrate that the presence of residual androgen
      action after long-term Hx results in enhanced germ-cell survival. Although the
      major blockage in cell viability occurs at midcycle steps in the long-term Hx
      rat, there are several other hormone-sensitive phases of spermatogenesis.

PMID- 9639051
TI  - Seminal vesicles are novel sites of luteinizing hormone/human chorionic
      gonadotropin-receptor gene expression.
AB  - The hypothesis that rat seminal vesicles may contain luteinizing hormone
      (LH)/human chorionic gonadotropin (hCG) receptors was tested by means of a number
      of different techniques. Northern blotting demonstrated that rat seminal vesicles
      contained multiple LH/hCG-receptor transcripts. In situ hybridization revealed
      that these transcripts were present primarily in the principal epithelial cells
      lining the lumen. Western immunoblotting detected proteins, two of which
      disappeared (80 and 46 kDa) and another of which decreased (30 kDa) after
      preabsorption of the receptor antibody with excess receptor peptide. Ligand
      blotting showed that 125I-hCG could bind only to an 80-kDa protein and that this
      binding was inhibited by coincubation with excess unlabeled hCG.
      Immunocytochemistry demonstrated that LH/hCG-receptor protein was present
      primarily in the principal epithelial cells. In conclusion, our data demonstrate
      that seminal vesicles contain LH/hCG receptors, thus making this previously
      unsuspected male accessory reproductive organ a potential target of direct
      regulation by LH.

PMID- 9639053
TI  - Neuronal nitric oxide synthase in the canine prostate: aging, sex steroid, and
      pathology correlations.
AB  - Nitric oxide synthase (NOS) is expressed in the prostate of various species,
      including humans. NOS catalyzes the production of nitric oxide (NO), which may
      function in prostatic smooth-muscle relaxation. To investigate further the role
      of NO in the prostate, we examined neuronal NOS expression in the aging canine
      prostate, after hormonal perturbation, and correlated these results with
      histopathologic findings. The study comprised the following treatment groups:
      intact dogs (treatment group 1, n = 6); dogs who were castrated at 7 days of age
      and received testosterone and estrogen replacement at 2 years of age (treatment
      group 2, n = 10); and dogs who were castrated at 2 years of age and received
      testosterone and estrogen replacement at 2 years of age (treatment group 3, n =
      9). Studies were done on prostates removed from dogs after euthanasia at 6 years
      of age. In treatment group 1, complex benign prostatic hyperplasia (BPH) was
      observed in all specimens. In treatment group 2, atrophy was observed in 70%,
      normal prostate with small areas of hyperplasia in 20%, and BPH in 10% of
      specimens. In treatment group 3, atrophy was observed in 78%, normal histology
      with small areas of hyperplasia in 11%, and BPH in 11% of specimens. Neuronal NOS
      localizations were confirmed by western blot analysis and by immunohistochemistry
      in 0% and 17%, respectively, of specimens in treatment group 1, in 60% and 70%,
      respectively, of specimens in treatment group 2, and in 67% and 71%,
      respectively, of specimens in treatment group 3. Neuronal NOS immunoreactivity
      was localized in histologically normal prostates of four intact, young-adult
      control dogs (2 years of age). For all treatment groups, neuronal NOS
      immunoreactivity was confirmed by western blot in 86% of atrophic prostates but
      in no prostates with BPH (P < 0.001), and it was confirmed by
      immunohistochemistry in 75% of atrophic prostates but in only 13% of prostates
      with BPH (P < 0.02). These data suggest that, in the canine prostate, NO release
      relates to growth and pathology. Low levels of neuronal NOS expression in BPH
      tissue, compared with higher levels in atrophic tissue, suggest that neuronal NOS
      expression is down-regulated in the prostate with benign cellular proliferation
      whereas it is maintained or possibly up-regulated in the prostate with prostatic
      involution. Whether altered neuronal NOS expression contributes to the
      pathogeneses of BPH and prostatic involution or whether it occurs as a
      consequence of these processes requires further investigation.

PMID- 9639052
TI  - Ethnic differences in testicular structure and spermatogenic potential may
      predispose testes of Asian men to a heightened sensitivity to steroidal
      contraceptives.
AB  - Spermatogenesis in Asian men appears to be more susceptible to suppression by
      steroidal contraceptives administered in clinical trials than spermatogenesis in
      Caucasian men. The objective of this study was to determine whether ethnic
      differences exist in testicular structure and spermatogenic potential that might
      predispose Asians to a high sensitivity to steroidal contraceptives. Testes from
      12 Chinese men were compared to those from 8 Hispanic men and 12 non-Hispanic
      Caucasian men of ages 29+/-3, 30+/-2, and 29+/-3 years, respectively. Testes were
      fixed by vascular perfusion with glutaraldehyde, further fixed in osmium,
      embedded in Epon, and evaluated by stereology using 0.5-microm sections stained
      with toluidine blue. Homogenates of fixed testes were evaluated for the number of
      Sertoli cells and the daily sperm production based on pachytene primary
      spermatocytes (PDSP) or spermatids with spherical nuclei (DSP). Paired
      parenchymal weight was less (P < 0.05) in Chinese men than in Hispanic or
      Caucasian men. The PDSP per gram of parenchyma was lower (P < 0.05) and the DSP
      per gram tended to be lower in Chinese men than in other groups. The histologic
      appearance, volume density, and length per man of seminiferous tubules were the
      same among the ethnic groups; however, the diameter of seminiferous tubules was
      less (P < 0.05) in Chinese than in Hispanic or Caucasian men. The PDSP per man
      and the DSP per man were lower (P < 0.05) in Chinese than in Hispanic or
      Caucasian men. The number of Sertoli cells per gram was higher (P < 0.05) in
      Chinese or Caucasian men than in Hispanic men, but the number of Sertoli cells
      per man was lower (P < 0.05) in Chinese men than in Hispanic or Caucasian men.
      Sertoli cell function, measured as the number of germ cells accommodated by a
      single Sertoli cell, was lower (P < 0.05) in Chinese men than in Caucasian men.
      The volume density of Leydig cell cytoplasm was greatest (P < 0.05) in Chinese
      men, but the number of Leydig cells was similar among the ethnic groups. Hence,
      smaller testes coupled with reduced Sertoli cell number and function and reduced
      daily sperm production could predispose Asian men to have a heightened negative
      response of testes to steroidal contraceptives, as compared to Caucasian men.
      Dampening (by exogenous androgens) of any physiological benefit to
      spermatogenesis that a high volume density of Leydig cell cytoplasm may bestow on
      the human testis (that Asian men may have evolved to require) would exacerbate
      ethnic differences in the spermatogenic response to hormonal contraceptives.

PMID- 9639054
TI  - Expression of 140-kDa neural cell adhesion molecule in developing testes in vivo
      and in long-term Sertoli cell-gonocyte cocultures.
AB  - The basis for cell-cell adhesion in the seminiferous epithelium of the developing
      testis is doubtless critical in supporting events that are essential for the
      onset and maintenance of normal spermatogenesis. In this study, we applied
      immunoblotting and immunolocalization approaches for the following reasons: 1) to
      ask whether neural cell adhesion molecule (NCAM) underlies cell-cell interactions
      in vivo, as we previously showed for cells in vitro, 2) to characterize the
      isoform or isoforms of NCAM expressed during testicular development, and 3) to
      study NCAM expression in long-term Sertoli cell-gonocyte cocultures and to
      compare and contrast this pattern of expression with that in vivo. Our findings
      indicate that NCAM is found ubiquitously at cell-cell interfaces within the
      seminiferous cord from birth through day 10 and thereafter is restricted to
      interstitial cells. Moreover, only polysialic acid-negative 140-kDa NCAM is
      expressed in the testis or in coculture, an isoform whose properties are
      compatible with the concept of NCAM as both a direct modifier of cell function
      and an indirect influence on cell responses mediated by other external factors.
      In addition, we found that germ cells, potentially gonocytes or Type A
      spermatogonia, persist in long-term cocultures maintained for 15 days after
      isolation from 5-day-old rat pups and that NCAM continues to be expressed at high
      levels in these cultures. This observation is in marked contrast to our
      observation that NCAM gradually decreases and eventually disappears in vivo by
      postnatal day 15. Thus, our findings indicate that 140-kDa NCAM is prominent in
      neonatal testes but is down-regulated by as yet unidentified mechanisms
      thereafter. Our findings also indicate that down-regulation of NCAM fails to
      occur in hormone- and serum-free Sertoli cell-germ cell cocultures.

PMID- 9639055
TI  - Glutamate transport and storage in synaptic vesicles.
AB  - Glutamate plays an important metabolic role in virtually every vertebrate cell.
      In particular, glutamate is the most common excitatory neurotransmitter in the
      vertebrate central nervous system. As such, the mechanism by which glutamate is
      diverted from its normal metabolic activities toward its role as a
      neurotransmitter has, in recent years, been systematically investigated. In
      glutamatergic nerve endings, synaptic vesicles accumulate and store a proportion
      of the cellular glutamate pool and, in response to appropriate signals, release
      glutamate into the synaptic cleft by exocytosis. Glutamate accumulation is
      accomplished by virtue of a glutamate uptake system present in the synaptic
      vesicle membrane. The uptake system consists of a transport protein, remarkably
      specific for glutamate, and a vacuolar-type H+-ATPase, which provides the
      coupling between ATP hydrolysis and glutamate transport. The precise manner in
      which the glutamate transporter and H+-ATPase operate is currently the subject of
      debate. Recent data relevant to this debate are reviewed in this article.
      Additionally, pharmacological agents thought to specifically interact with the
      vesicular glutamate transporter are discussed. Finally, a newly discovered,
      endogenous inhibitor of vesicular uptake, inhibitory protein factor (IPF), is
      discussed with some speculations as to its potential role as a presynaptic
      modulator of neurotransmission.

PMID- 9639056
TI  - Pathophysiological effects of dietary essential fatty acid balance on neural
      systems.
AB  - Dietary fatty acid balance has been revealed to affect neural functions as well
      as chronic diseases such as cancer, cerebro- and cardiovascular diseases, and
      allergic hyper-reactivity. In this review, we focused on the pathophysiological
      effects of n-6 and n-3 fatty acids on brain functions. Long-term n-3 fatty acid
      deficiency in the presence of n-6 fatty acids has been shown to affect learning
      behavior, drug sensitivity and retinal functions. Some membrane enzymes and ion
      channel functions have been shown in experimental animals to be regulated by
      membrane fatty acid modifications. We also summarized the effects of these fatty
      acids in diets on human psychotic aspects and brain diseases. Although
      biochemical mechanisms remain to be elucidated, investigations on the effect of
      dietary fatty acids on neural networks may provide an important clue to clarify
      complex brain functions.

PMID- 9639057
TI  - Stimulatory guanine nucleotide-binding protein in failing heart of hamsters and
      rats.
AB  - The role of the stimulatory guanine nucleotide-binding protein (Gs) in heart
      failure is unclear. We therefore determined the amount of protein and mRNA of Gs
      in the failing myocardium using two animal models: the BIO 53.58 hamster, a model
      of genetic cardiomyopathy, and adriamycin-treated rats (ADR rats), a model of
      secondary cardiomyopathy. The maximal number of myocardial beta-adrenoceptors in
      the BIO 53.58 hamsters as well as in the ADR rats was significantly lower than
      that in the respective controls, indicating that the beta-adrenoceptors were down
      regulated in heart failure. Analysis by Western blot and Northern blot revealed a
      significant decrease in Gs protein and mRNA in the BIO 53.58 hamsters relative to
      the control. There were no differences in the level of Gs protein or mRNA in the
      ADR rats vs the controls. The functional activity of Gs was investigated by
      measuring adenylate cyclase activity. The activity of adenylate cyclase in
      response to stimulation by sodium fluoride or forskolin was decreased in the BIO
      53.58 hamsters relative to control animals, whereas no differences were observed
      in the ADR rats vs the controls. Thus, alterations in Gs in the failing heart
      appear to differ according to its cause.

PMID- 9639058
TI  - Protective effects of ranolazine, a novel anti-ischemic drug, on the hydrogen
      peroxide-induced derangements in isolated, perfused rat heart: comparison with
      dichloroacetate.
AB  - The effect of ranolazine, a novel anti-ischemic drug that stimulates the activity
      of pyruvate dehydrogenase, on hydrogen peroxide (H2O2)-induced mechanical and
      metabolic derangements was studied in isolated rat heart and compared with that
      of dichloroacetate (DCA), an activator of pyruvate dehydrogenase. The heart was
      perfused aerobically by the Langendorff's technique at a constant flow and driven
      electrically. H2O2 (600 microM) decreased the left ventricular developed pressure
      and increased the left ventricular end-diastolic pressure (i.e., mechanical
      dysfunction), decreased the tissue level of adenosine triphosphate (i.e.,
      metabolic derangement), and increased the tissue level of malondialdehyde (MDA)
      (i.e., lipid peroxidation). These mechanical and metabolic derangements induced
      by H2O2 were significantly attenuated by ranolazine (10 or 20 microM). On the
      other hand, DCA (1 mM) was ineffective in attenuating the H2O2-induced mechanical
      and metabolic derangements. Ranolazine, however, did not modify the tissue MDA
      level, which was increased by H2O2. In the normal (H2O2-untreated) heart,
      ranolazine did not alter the mechanical function and energy metabolism. These
      results demonstrate that ranolazine attenuates mechanical and metabolic
      derangements induced by H2O2. It is suggested that the protective action of
      ranolazine against the H2O2-induced derangements is due to neither the energy
      sparing, DCA-like, nor anti-oxidant effects.

PMID- 9639059
TI  - Comparison of atypical beta3-adrenoceptor agonists with their respective
      metabolic activities in rat white adipocytes.
AB  - The metabolic activities of four types of beta3-adrenoceptor (AR) agonists,
      BRL35135A, BRL28410, ICI215001 and CL316243, were compared with those of other
      beta1- and beta2-AR agonists in rat white adipocytes. All the beta3-AR agonists
      caused cAMP formation, free fatty acid release and 2-deoxyglucose uptake; the
      maximum activity levels were similar except for ICI215001, which was lower.
      However, the magnitude of potency and selectivity of these agonists differed. The
      most potent and selective beta3-agonist was CL316243. Metabolic activities and
      Northern blotting showed that there were three beta-AR subtypes that were coupled
      to adenylyl cyclase and contributed to the induction of lipolysis and glucose
      uptake. The rank order of the amounts of beta-AR subtypes was beta3 >>beta1>
      beta2. However, the physiological functions of beta-AR subtypes were essentially
      similar in rat white adipocytes. On the other hand, cAMP accumulation and
      Northern blotting showed that human adipocytes predominantly contained beta2-AR,
      with far lower levels of beta1- and beta3-ARs. These findings suggested that the
      beta3-AR plays an important role in energy metabolism and thermogenesis in which
      cross talk exists between beta1- and beta3-ARs in rat adipocytes, while beta2-AR
      is the most important for the lipolysis regulation in human subcutaneous
      adipocytes.

PMID- 9639060
TI  - Affinity of mosapride citrate, a new gastroprokinetic agent, for 5-HT4 receptors
      in guinea pig ileum.
AB  - We examined the binding affinity of mosapride citrate (mosapride) (4-amino-5
      chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholinyl]me thyl] benzamide citrate),
      a novel gastroprokinetic agent, for the 5-hydroxytryptamine (5-HT) 4 receptors in
      guinea pig ileum using a selective 5-HT4-receptor radioligand, [3H]GR113808. In
      membrane preparations from longitudinal muscle with myenteric plexus in guinea
      pig ileum, specific [3H]GR113808 binding revealed a single saturable site of high
      affinity (Kd=0.28 +/-0.02 nM, Bmax = 45+/- 3 fmol/mg protein). Mosapride and
      other 5-HT4-receptor agonists inhibited the specific binding of [3H]GR113808 in
      guinea pig ileum. The 5-HT4 agonists examined displayed the following inhibition
      potency order: BIMU-8 > cisapride > mosapride > renzapride > 5-HT > zacopride >
      metoclopramide. Mosapride exhibited monophasic inhibition of the specific
      [3H]GR113808 binding in the ileum (Ki value: 84.2 nM). The presence of mosapride
      (30 nM) significantly increased the Kd value to 0.44+/-0.05 nM in the Scatchard
      analysis of [3H]GR113808 binding. Bmax of [3H]GR113808, however, was not affected
      (48 +/-4 fmol/mg protein) by mosapride. As for the affinity of mosapride, the
      addition of GppNHp (100microM) slightly increased the Ki value to 104 nM. These
      results indicate that mosapride has an affinity for 5-HT4 receptors in guinea pig
      ileum in the radioligand binding study.

PMID- 9639061
TI  - Vascular alpha1-adrenoceptor subtype selectivity and alpha1-blocker-induced
      orthostatic hypotension.
AB  - Newly developed alpha1-adrenoceptor antagonists including naftopidil are free
      from the "prazosin-like" side effect of orthostatic hypotension and associated
      symptoms. We investigated the mechanism for the differential effects of
      naftopidil and prazosin on the development of postural hypotension, with special
      attention on their selectivity for the alpha1-adrenoceptor subtype. We observed
      that head-up tilt caused a similar extent of drop in mean arterial pressure in
      control, naftopidil (1 mg/kg)- or prazosin (10 microg/kg)-treated rats; however,
      the tilt-induced postural hypotension was recovered within 2 min in the
      naftopidil-treated group, but not in the prazosin-treated group. Comparing an
      inhibitory effect on noradrenaline-induced contraction in the rat aorta and
      portal vein, we found that naftopidil was sixfold less potent in the portal vein,
      while prazosin showed similar potency in both tissues. Reverse transcription
      polymerase chain reaction analysis showed that the expression of alpha1d
      adrenoceptor mRNA predominated in the aorta, while that of alpha1b-adrenoceptor
      mRNA predominated in the portal vein. Using cloned rat alpha1-adrenoceptor
      subtypes, we found that naftopidil was selective for the alpha1d-subtype with
      approximately ninefold higher affinity than at the other subtypes. These results
      show that the pharmacological character of naftopidil, combined with the
      differential expression of the alpha1-adrenoceptor subtype in the artery and the
      vein, may partly explain the differential effect of naftopidil and prazosin on
      head-up tilt-induced hemodynamic responses.

PMID- 9639062
TI  - Effects of SS320A, a new cysteine derivative, on the change in the number of
      goblet cells induced by isoproterenol in rat tracheal epithelium.
AB  - We examined the effects of SS320A ((-)-(R)-2-amino-3-(3
      hydroxypropylthio)propionic acid), a new cysteine derivative, on the change in
      the number of goblet cells induced by isoproterenol in rat tracheal epithelium.
      Four types of goblet cells were characterized in tracheal epithelium according to
      their size and staining affinity with Alcian blue (AB) / periodic acid Schiff
      (PAS). When each rat was given a single daily injection of isoproterenol (0.05
      mg/kg, i.p.) for 14 days, a significant increase was observed in AB/PAS-positive
      cells that were recognizable as goblet cells in tracheal epithelium. When SS320A
      (10-100 mg/kg, p.o.) or propranolol (1 mg/kg, s.c.) was administered before each
      injection of isoproterenol, the increase in the number of goblet cells induced by
      isoproterenol was significantly inhibited. There was no difference between male
      and female rats with regard to this inhibitory action. On the other hand,
      ambroxol, bromhexine, L-cysteine ethyl ester and S-carboxymethylcysteine (100
      mg/kg, p.o., respectively), which are used as expectorants, had no inhibitory
      effects on the isoproterenol-induced change in the number of goblet cells. Four
      metabolites (M1-M4) of SS320A in rats also failed to inhibit the change induced
      by isoproterenol. These data suggest that SS320A itself may have a beneficial
      effect against mucus hypersecretion in chronic respiratory diseases.

PMID- 9639063
TI  - Cardioprotective effects of an angiotensin-converting-enzyme inhibitor,
      imidapril, and Ca2+ channel antagonist, amlodipine, in spontaneously hypertensive
      rats at established stage of hypertension.
AB  - The present study was performed to compare cardioprotective effects of an
      angiotensin-converting-enzyme inhibitor, imidapril, and of a Ca2+ channel
      antagonist, amlodipine, against the cardiac hypertrophy in male spontaneously
      hypertensive rats (SHRs) at the established stage of hypertension. Fifteen-week
      old SHRs were given imidapril (2 and 5 mg/kg/day) or amlodipine (10 mg/kg/day) by
      gavage for 8 weeks. Three hours after the 1st treatment, imidapril moderately
      reduced blood pressure without changing heart rate, while amlodipine caused a
      marked reduction in blood pressure accompanied by transient tachycardia. At the
      end of the treatments, ventricular weight in the imidapril-treated groups was
      markedly lower, but that in the amlodipine-treated group was only slightly lower
      than that in the vehicle-treated group. Myocardial collagen content in the
      imidapril-treated group tended to be decreased, and significant reduction was
      observed in the low-dose group. In another experiment, the isolated heart of the
      imidapril-treated animals demonstrated better cardiac compliance than that in the
      vehicle-treated animals. In contrast, amlodipine failed to improve cardiac
      function. The present results suggest that imidapril possesses advantageous
      effects to prevent cardiac hypertrophy and deteriorated cardiac function in SHRs
      of established stage of hypertension as compared with amlodipine.

PMID- 9639064
TI  - Difference in inhibitory effects of dexamethasone and cyclosporin A on Sephadex
      bead-induced airway hyperresponsiveness and inflammation in rats.
AB  - We investigated the effects of dexamethasone and cyclosporin A on Sephadex bead
      (Sephadex G-200, Sephadex)-induced airway hyperresponsiveness (AHR) and
      inflammation in rats. Sephadex (0.5 mg/animal) was intravenously administered on
      days 0, 2 and 5. Bronchoalveolar lavage, histological study and measurement of
      AHR were performed on day 7. Dexamethasone (0.1, 1 and 10 mg/kg, p.o. x 3) and
      cyclosporin A (0.1, 1 and 10 mg/kg, s.c. x 3) clearly inhibited the increase in
      eosinophils in bronchoalveolar lavage fluid after Sephadex injection. On
      histological study, pulmonary eosinophilia, granulomatous arteritis with
      horseshoe-shaped multinuclear giant cell formation and goblet hyperplasia were
      observed after Sephadex injection. Both dexamethasone (10 mg/kg x 3) and
      cyclosporin A (10 mg/kg x 3) inhibited these findings and an increase in
      eosinophil peroxidase in the lung. Dexamethasone dose-dependently inhibited AHR
      induced by Sephadex, and completely suppressed it at a dose of 1 mg/kg (x 3).
      Cyclosporin A, however, did not inhibit AHR even at a dose of 10 mg/kg ( x 3).
      These results show that there is a difference between dexamethasone and
      cyclosporin A in the inhibitory effect on Sephadex-induced AHR, and they suggest
      that eosinophils are not directly associated with the development of AHR after
      Sephadex injection.

PMID- 9639065
TI  - Coronary artery diameter increase induced by a phosphodiesterase 5 inhibitor,
      E4021, in conscious pigs.
AB  - The effects of intravenous infusions of 1, 3 and 10 microg/kg/min of the
      phosphodiesterase 5 inhibitor, E4021, at 30-min intervals on coronary artery
      diameter were studied in 8 conscious pigs monitored with a pair of piezoelectric
      crystals. The highest dose increased the diameter by 2.9 +/-0.5% (P <0.01 vs
      vehicle) of the baseline diameter, with a significant decrease in mean pulmonary
      arterial pressure. However, there were no changes in mean aortic pressure and
      heart rate. Additionally, E4021 significantly prolonged the duration of the
      diameter increase induced by nitroglycerin. Thus, phosphodiesterase 5 inhibition
      causes coronary artery diameter increase and produces an amplifying effect with
      nitroglycerin.

PMID- 9639066
TI  - Inhibition by [Arg8]-vasopressin of long term potentiation in guinea pig
      hippocampal slice.
AB  - We examined the effects of [Arg8]-vasopressin (AVP) on long term potentiation
      (LTP) of the field excitatory postsynaptic potentials at CA1 and CA3 synapses in
      adult guinea pig hippocampal slices. AVP (10 nM) depressed the magnitude of LTP
      without any effects on basal responses at both synaptic pathways. The depressive
      effect by AVP at CA1 synapses appears to be receptor-mediated since it was
      inhibited by an AVP V1-receptor antagonist, [Pmp1,Tyr(Me)2]-AVP. From these
      results, AVP may play an inhibitory role on the induction of LTP via V1 receptors
      in the guinea pig hippocampus.

PMID- 9639067
TI  - HIV and HIV dementia.

PMID- 9639068
TI  - SIV infection of macaques--modeling the progression to AIDS dementia.
AB  - AIDS dementia complex affects 15-20% of HIV-infected adults and a greater
      percentage of HIV-infected children. Whether or not an HIV-infected individual
      develops neurological disease and how early in infection the clinical signs
      appear is most likely the net result of both viral virulence factors and host
      factors. Important viral factors include cell tropism and sequences that
      determine neurovirulence. The host factors include the cellular expression of
      viral co-receptors and maintenance of competent immune responses. The
      pathogenesis of AIDS dementia complex is difficult to study in the human host
      because of the difficulty in identifying acutely infected individuals and the
      inaccessibility of human brain tissue for examination during infection. The
      SIV/macaque model is excellent for the study of viral virulence factors and host
      responses to infection. This review outlines how the SIV/macaque model has been
      used to identify viral factors that are important for the development of
      neurological disease, to determine when HIV enters the brain, and to characterize
      the host immune responses affecting virus entry to the CNS and the development of
      neurological disease.

PMID- 9639069
TI  - Simian immunodeficiency virus encephalitis in rhesus macaques is associated with
      rapid disease progression.
AB  - Central nervous system (CNS) disease is a major feature of simian
      immunodeficiency virus (SIV) infection of macaques. To define the spectrum of CNS
      lesions in SIV-infected macaques and the potential associations with viral strain
      and disease course, we performed a retrospective analysis of necropsies on 124
      macaques with SIV-induced AIDS. Histologic evidence of CNS disease was observed
      in 71 (57.3%) of the 124 animals. SIV encephalitis was the most common CNS lesion
      occurring in 43.7% (31/71) of the animals with CNS disease and 25% of all
      animals. The incidence of SIVE correlated significantly with shortened survival
      (P=0.0207). In addition, SIVE was seen in 42.9% (15/35) of rapid progressors
      (animals that died within 200 days) compared to only 18% (16/89) of normal
      progressors (animals that lived longer than 200 days) (P=0.011). Animals with
      SIVE had higher viral loads in peripheral blood than those that did not, but this
      difference did not reach statistical significance. Similarly, while animals
      infected with uncloned SIVmac251 had a higher incidence of SIVE (27.5%; 14/51)
      than animals infected with molecularly cloned SIVmac239 and its T-cell tropic
      derivatives (18.5%; 10/54) this difference was not statistically significant. In
      this study rapid disease progression and SIVE were highly correlated making
      separation of viral determinants of virulence from those of neurovirulence
      difficult.

PMID- 9639070
TI  - Efficient infection of brain microvascular endothelial cells by an in vivo
      selected neuroinvasive SIVmac variant.
AB  - A neuroinvasive/neuropathogenic SIV variant termed SIVmac182 was previously
      isolated and characterized (Watry et al, 1994). This neuroinvasive strain was
      derived from the uncloned strain SIVmac251 through serial animal passage of
      infected microglia, unlike previously reported neurovirulent strains.
      Importantly, the virus described here was isolated from a strain which already
      demonstrates limited neuroinvasiveness in vivo, through a route of inoculation
      which exerts selective pressure for variants in the periphery that can naturally
      cross the blood-brain barrier and gain access to the brain. Examination of animal
      tissues indicated that the neuroinvasive strain was capable of replicating in
      brain microvascular endothelial cells (BMEC). Therefore, we developed an in vitro
      model of BMEC infection in which to examine mechanisms of virus neuroinvasiveness
      and neuropathogenicity as well as to address mechanisms of HIV-induced dementia.
      Results obtained with this in vitro system indicate that growth in BMEC may
      predict neuroinvasiveness in vivo, and furthermore, that brain passage of virus
      results in the generation of neuroinvasive strains which demonstrate an increased
      efficiency of BMEC infection in vitro.

PMID- 9639071
TI  - Neuronal apoptosis induced by HIV-1 Tat protein and TNF-alpha: potentiation of
      neurotoxicity mediated by oxidative stress and implications for HIV-1 dementia.
AB  - Apoptosis of neurons and non-neuronal cells has been demonstrated in the brain of
      AIDS patients with dementia. Previous studies suggest that the apoptotic stimuli
      are likely to be soluble factors. Several candidates for the soluble factors that
      lead to neuronal apoptosis in HIV-1 infection have been proposed, including the
      HIV-1 Tat protein and TNF-alpha. The mechanisms that lead to neuronal apoptosis
      in the brain of AIDS patients in vivo, may involve the combined effects of more
      than one pro-apoptotic factor. In this study, we examine whether exposure of
      primary human neurons to the combination of HIV-1 Tat and TNF-alpha can
      potentiate the induction of neuronal apoptosis compared with exposure to either
      factor alone. TNF-alpha was shown to potentiate the induction of neuronal
      apoptosis by HIV-1 Tat via a mechanism that involves increased oxidative stress.
      Antioxidants inhibited, but did not completely abolish the induction of neuronal
      apoptosis by Tat, suggesting that other mechanisms are also likely to be
      involved. These findings suggest that soluble HIV-1 Tat and TNF-alpha may play a
      role in neuronal apoptosis induced by HIV-1 infection of the CNS, particularly
      when present in combination. Our findings further suggest that one mechanism
      whereby combinations of pro-apoptotic factors may potentiate the induction of
      neuronal apoptosis in the brain of AIDS patients is by increasing oxidative
      stress. Understanding the role of oxidative stress and other mechanisms that lead
      to apoptosis in HIV-1 infection of the CNS may advance the development of new
      therapeutic strategies to prevent neuronal cell death and improve neurologic
      function in AIDS patients.

PMID- 9639072
TI  - Anomalies in Nef expression within the central nervous system of HIV-1 positive
      individuals/AIDS patients with or without AIDS dementia complex.
AB  - In determining levels of expression of HIV-1 Nef protein within the central
      nervous system (CNS) we assessed antibody responses to the protein both
      peripherally and in CNS. Antibodies to Nef were not detected within the CNS
      despite detection of antibodies to both gp41 and Nef in peripheral blood and
      representative virus isolates derived from CNS and peripheral blood (PB) samples
      containing full length nef sequence and virus-infected cells expressing Nef
      protein. We conclude from this that expression of Nef within the CNS is such that
      little or no antibody production occurs and that these differences indicate that
      Nef protein may not be directly contributing to the AIDS dementia complex.
      Expression of Nef protein in PHA-activated peripheral blood mononuclear cells
      from CNS derived isolates was different to that of coincidental PB derived
      isolates in that partial surface expression was observed for the latter. The
      results suggest that antigenic presentation of Nef within the CNS is anomalous
      and that Nef protein expression, at least for the limited number of in vitro
      derived isolates tested, has a different localization pattern.

PMID- 9639073
TI  - Chemokine receptors in the human brain and their relationship to HIV infection.
AB  - Chemokine receptors have been recently identified as the important co-factors
      which in conjunction with CD4, mediate entry of HIV into its target cells. The
      brain is one of the most prominent targets of HIV infection, where it leads to
      HIV encephalitis (HIVE) and HIV-associated dementia. Knowledge of the
      distribution, physiology, and pathology of chemokines and chemokine receptors in
      the human brain is fundamental for understanding the pathogenesis of the
      interaction between HIV and the central nervous system (CNS). There is also
      increasing evidence that chemokine receptors expression in the CNS increases
      during pathological, especially inflammatory, conditions. The major co-factors
      for HIV infection, CCR5, CCR3, and CXCR4 have been detected in the human brain in
      a variety of cell types including microglia, astrocytes, neurons, and vascular
      endothelial cells. Furthermore, antibodies to chemokine receptors can also block
      HIV infectivity in cultured CNS cells. This indicates that chemokine receptors
      are likely to have a functional role in the pathogenesis of HIVE.

PMID- 9639074
TI  - Sp1 and related factors fail to interact with the NF-kappaB-proximal G/C box in
      the LTR of a replication competent, brain-derived strain of HIV-1 (YU-2).
AB  - The HIV-1 LTR promoter proximal G/C box array has been demonstrated to function
      by interacting with the Sp1 transcription factor family whose members can act as
      either activators or repressors of transcription. In this regard, we have
      examined the interaction of the HIV-1 Sp binding sites with nuclear factors that
      are present in cell types that support HIV-1 replication, including those of
      lymphocytic, monocytic, and astrocytic origin. As determined by electrophoretic
      mobility shift (EMS) competition analyses using oligonucleotides containing the
      sequences of each of the Sp1 sites of HIV-1 strain LAI, the NF-kappaB-proximal Sp
      site (site III) displayed the highest binding activity compared to sites I and II
      with regard to Sp1 and related factors present in lymphocytic (Jurkat) and
      astrocytic (U-373 MG) nuclear extracts. Sp1 and two Sp3 isoforms were detected as
      the primary cellular constituents of DNA-protein complexes formed with the NF
      kappaB-proximal site. Only modest differences in Sp1:Sp3 binding ratios were
      observed when this site was reacted with either astrocytic or lymphocytic nuclear
      extract. However, when nuclear extracts derived from two monocytic cell types
      that differ in the degree of differentiation were reacted with the HIV-1 LAI Sp
      site III, a large difference in Sp1 and Sp3 binding was observed. To determine if
      naturally occurring and replication-competent strains of HIV-1 contain base pair
      alterations within the Sp elements that affect the ability of the site to
      interact with Sp1 and related factors, a series of Sp site III variants were
      constructed and examined by EMS analyses. One of these sites, obtained from the
      published sequence of the YU-2 strain (a brain-derived macrophage tropic strain
      of HIV-1), displayed almost no Sp1 or Sp3 binding activity as a result of a
      single base pair alteration in Sp site III. This base-pair alteration, when
      placed in the context of an HIV-1 LAI LTR-luciferase construct, resulted in a 40
      50% reduction in LTR activity in transiently transfected Jurkat and U-373 MG
      cells. Overall, these results suggest that specific G/C box sequence alterations
      present in the brain-derived HIV-1 variant YU-2, or possibly other brain-derived
      variants, may exhibit altered replication properties as a result of the low
      affinity of the NF-kappaB-proximal G/C box for members of the Sp transcription
      factor family.

PMID- 9639075
TI  - Survival prolongation in HIV-associated progressive multifocal
      leukoencephalopathy treated with alpha-interferon: an observational study.
AB  - A retrospective chart review was conducted to determine the effect of alpha
      Interferon (alpha-IFN) on disease progression, symptom palliation, and survival
      in HIV-associated Progressive Multifocal Leukoencephalopathy (PML). METHODS:
      Subjects were HIV seropositive patients diagnosed with PML at the Johns Hopkins
      Hospital between 1985 and July of 1986. Diagnostic criteria for PML included both
      clinical symptomatology and histologic or radiographic confirmation. All patients
      with concomitant CNS infections were excluded. Patients receiving a minimum
      treatment of 3 weeks of 3 million units of alpha-IFN daily were compared to
      untreated historical controls. From 104 PML cases reviewed, 77 met the defined
      criteria for PML. Twenty-one patients had received open-label alpha-IFN treatment
      in a non-randomized manner for at least 3 weeks, and 32 met criteria for
      inclusion in the untreated group as historical controls. Deceased treated
      patients were comparable to deceased untreated patients with respect to age,
      gender, race, HIV risk factors, AIDS-defining illnesses, and CD4+ counts. CD4+
      counts and use of anti-retroviral medications within 6 months of PML onset were
      higher among those who were living at the time of the study. RESULTS: Among
      deceased patients, median survival of treated patients was 127.5 days longer than
      that of untreated patients (Chi-square=4.21, P=0.04). When living and deceased
      treated patients were combined, the median survival was 325 days (range 35 -
      1634) versus 121 days (range 46 - 176) in untreated patients (Chi-square=13.47, P
      < 0.001). When survival times in untreated patients were left-censored to account
      for possible survivorship bias in treated patients, survival in treated patients
      remained significantly prolonged (325 days versus 175.5 days, Chi-square=4.65,
      P=0.03). In addition, use of alpha-IFN was associated with a significant delay in
      the onset of memory loss (Chi-square=8.59, P < 0.01). Seven alpha-IFN treated
      patients showed sustained remissions of several months to over a year, with
      documented improvements in mental status, aphasia, dysarthria, dysphagia,
      paresis, and dyscoordination. Moreover, four IFN-treated patients had evidence of
      MRI lesion regression, although this was not always correlated with clinical
      remission. Four of 32 untreated patients also reported transient symptomatic
      improvements. CONCLUSION: This open-label study suggests that alpha-IFN may delay
      progression, palliate symptoms, and significantly prolong survival in HIV
      associated PML, and we therefore suggest that a controlled clinical trial is
      warranted.

PMID- 9639076
TI  - Short-term side effects of stimulant medication are increased in preschool
      children with attention-deficit/hyperactivity disorder: a double-blind placebo
      controlled study.
AB  - Preschool children with attention-deficit/hyperactivity disorder (ADHD) (27 boys,
      5 girls, mean age 4 years 10 months) participated in a double-blind placebo
      controlled crossover drug study to assess the side effects of methylphenidate.
      Children received twice daily, for at least 1 week each, placebo, 0.3 mg/kg
      methylphenidate, and 0.5 mg/kg methylphenidate. Side effects were monitored by a
      parent rating scale designed for medication studies. In general, methylphenidate
      was tolerated relatively well, with no children withdrawing because of adverse
      effects. Of 17 childhood behaviors usually associated with side effects, 8
      behaviors showed significant changes, generally at the higher dose of
      methylphenidate. Interestingly, 3 of the side effects were associated with
      improved behavior. The number of side effects appeared higher than what is
      usually reported in a population of school-age children, but few parents reported
      them as being severe. Severe side effects were reported in less than 10% of the
      sample, with approximately as many reports of severe effects on placebo as on low
      and high doses of the medication. The results indicate that methylphenidate has a
      relatively low toxicity in preschool children (over the first 7-10 days), that
      some behavioral changes that might be viewed as side effects of methylphenidate
      are actually normal behaviors or ADHD behaviors in preschool children (e.g.,
      sociability), that these "side-effect" behaviors are more common in preschool
      than school-age children, that some "side effects" of methylphenidate are
      associated with improvements in behavior, and that preschool and school-age
      children may have different side effects of methylphenidate (e.g., mood changes
      and anxiety).

PMID- 9639077
TI  - Prevalence and patterns of psychotropic and anticonvulsant medication use in
      children and adolescents referred to residential treatment.
AB  - The prevalence and patterns of use of psychiatric and anticonvulsant medications
      were studied in 83 seriously emotionally disturbed children and adolescents at
      the time of their admission to a residential treatment facility. Youths (aged 5
      19, mean = 13.6 years), consecutively admitted over 17 months, were assessed for
      the prevalence and patterns of use of psychotropic and anticonvulsant treatments.
      At admission, 76% of the youths were receiving psychiatric pharmacotherapy, 40%
      with more than one psychiatric agent, and 15% with a combination of psychotropic
      and anticonvulsant medications. Frequently prescribed medications were
      neuroleptics (35 % of the medicated youths), sedative-hypnotics (26 %), and
      anticonvulsants (15%). Psychostimulants (16%) and antidepressants (22%) were
      under-prescribed relative to their diagnostic indications. Over 50 different
      medication combinations were used. The neuroleptic + lithium combination was most
      common (25 % of the polypharmacological treatments). Neuroleptics were the most
      commonly prescribed medication and mostly used for nonpsychotic, nontic, and
      nonbipolar indications (55% of neuroleptic trials). Neuroleptics were used
      primarily for aggression regardless of diagnosis. Neuroleptics were used more in
      symptomatic treatments than in treatments for indicated diagnoses. The high
      prevalence of psychiatric and antiepileptic medication use in children and
      adolescents admitted to a residential treatment facility, and especially the
      pattern of their use, raises questions about prescribing practices for youths
      entering residential treatment and about pediatric psychopharmacotherapy in
      general.

PMID- 9639078
TI  - Effectiveness of methylphenidate in Native American children with fetal alcohol
      syndrome and attention deficit/hyperactivity disorder: a controlled pilot study.
AB  - This pilot study was designed to assess the short-term effectiveness and side
      effects of methylphenidate in treating symptoms of attention deficit
      hyperactivity disorder (ADHD) in Native American children (5 to 12 years old)
      with documented fetal alcohol syndrome (FAS) or partial fetal alcohol syndrome.
      Using strict criteria for the diagnosis of FAS and ADHD, a randomized double
      blind cross-over study of two placebos and a fixed dose of methylphenidate was
      completed in 4 Native American children in a residential school. Each treatment
      condition lasted 5 days, and daily observational outcome measures, the Conners
      Parent Rating Scale (CPRS-48), and the Conners Teacher Rating Scale (CTRS-39),
      were employed. Methylphenidate significantly improved scores of the Hyperactivity
      Index Scale on the CPRS-48 and the CTRS-39 but not the Daydreaming-Attention
      score on the CTRS-39. Side effects were similar to those traditionally found in
      other populations. The promising preliminary results suggest that a more
      definitive study of methylphenidate in Native and non-Native children with FAS
      and ADHD is warranted.

PMID- 9639079
TI  - Risperidone for young children with mood disorders and aggressive behavior.
AB  - Open clinical treatment with risperidone was administered to a clinically
      heterogeneous group of 11 children and adolescents (age range 5.5-16 years, mean
      9.8 years) with concurrent presentation of affective symptoms (mostly suggestive
      of bipolar disorder), aggressive and violent behavior, and marked management
      problems. These patients had responded inadequately to several mood-stabilizing
      medications. In this outpatient sample, 8 of 11 children (73%) appeared to have
      therapeutic responses to risperidone. Risperidone doses were low (0.75-2.5 mg
      daily) and clinical responses were observed at times within days of receiving the
      medication. Improvement was clinically judged to be moderate to marked in 7 of 8
      children. In addition, the treatment of 2 children was stopped because of
      drowsiness; one also experienced a weight gain of 6 kg (13 lbs). An additional
      child with autism and aggressive behavior who lacked affective symptoms did not
      respond to risperidone. None of the children showed behavioral deterioration.
      Seven of the 8 responders were taking concurrent medications; including 4 on mood
      stabilizing medications (either lithium, carbamazepine, or valproic acid) in
      subtherapeutic doses. Even in combination with other medications, side effects at
      these doses were minimal and limited to mild sedation and, at times, troubling
      weight gain. Pending controlled studies, these preliminary findings suggest that
      risperidone--alone or in combination with mood stabilizers--may be of value in
      treating children and adolescents with mood disorders (especially subthreshold
      bipolar disorder) and aggressive behavior.

PMID- 9639080
TI  - Combination treatment with clomipramine and selective serotonin reuptake
      inhibitors for obsessive-compulsive disorder in children and adolescents.
AB  - Medication management of obsessive-compulsive disorder (OCD) has consisted of
      monotherapy with either clomipramine (CMI) or selective serotonin reuptake
      inhibitors (SSRIs) such as fluvoxamine, paroxetine, or sertraline. Frequently,
      OCD patients receiving monotherapy experience low treatment response rates and
      problematic side effects that may result in discontinuation or noncompliance.
      This open-label case series presents 7 patients (6 male, 1 female) ages 9 to 23
      years with OCD who were effectively treated with combination of CMI plus an SSRI.
      Treatment effects persisted through 5 to 22 months of follow-up from onset of
      combination therapy. The drug combination was effective in the 2 patients with
      OCD and no mood/anxiety comorbidity. Side effects appeared in 5 of 7 patients;
      cardiovascular side effects were the most common adverse effects. Two patients
      had prolongation of QTc intervals and 2 developed tachycardia while taking CMI
      and SSRI combinations. Other risks might include serotonin syndrome, manic
      switch, insomnia, and possibly headaches, EPS, and sexual dysfunction.
      Recommendations are made to monitor electrocardiograms, CMI blood concentrations,
      and vital signs in all cases because SSRIs can increase the blood levels of CMI
      and/or its active metabolite, desmethylclomipramine (DCMI). CMI could also
      potentially increase SSRI absorption and/or protein binding. The use of CMI and
      SSRI combination therapy was found to be more effective compared with their
      monotherapy in all 7 cases.

PMID- 9639081
TI  - Paroxetine treatment of trichotillomania in an adolescent.
AB  - The authors present a case report involving an adolescent with trichotillomania
      who was treated with paroxetine. A significant reduction in symptoms was apparent
      after two weeks of treatment. Dose was gradually increased to 30 mg of paroxetine
      per day, which was well tolerated without any significant adverse events. The
      authors discuss potential treatment implications of this case.

PMID- 9639082
TI  - Manic behaviors associated with fluoxetine in three 12- to 18-year-olds with
      obsessive-compulsive disorder.
AB  - In a sample of 40 youths (ages 11-17) with obsessive-compulsive disorder (OCD)
      and mood disorders who were treated with behavior therapy, 20 patients received
      serotonin reuptake inhibitors (SRIs) and 20 did not. In open-label clinical
      treatment, 30% of the patients (6/20) treated with SRIs developed manic or
      hypomanic symptoms (5/15 on fluoxetine, 1/1 on sertraline). Symptoms included
      impulsivity, grandiosity, pressured speech, and disinhibition and did not
      resemble akathisia or "behavioral activation." These behaviors emerged despite
      gradual dose elevation (2-5 mg/wk), conservative dosing (maximum 40 mg daily),
      and careful weekly outpatient monitoring of each patient. Fluoxetine-induced
      mania occurred at doses as low as 10 mg daily. It is unclear whether
      mania/hypomania would appear in OCD children without comorbid mood disorders or,
      alternatively, whether OCD is a stronger risk factor than mood disorder for manic
      switch in SRI-treated youths. Clinicians are advised to be aware of the risk and
      to be vigilant in monitoring manic and hypomanic behaviors when using SRIs to
      treat OCD in youth, even with low doses and gradual dose elevation.

PMID- 9639083
TI  - Gabapentin in the treatment of adolescent mania: a case report.
AB  - Gabapentin is a new antiepileptic drug with an unknown mechanism of action and
      very favorable pharmacokinetic and safety profiles. An increasing number of
      reports have described the successful use of gabapentin in bipolar disorder in
      adults. A 13-year-old boy with bipolar I disorder, manic episode, and ADHD, was
      treated with gabapentin 1,500 mg/day as add-on therapy to carbamazepine and
      showed a marked response within 1 month. He had previously failed a divalproex
      trial, could not tolerate lithium, and carbamazepine could not control his
      symptoms and induced a low WBC. He remained euthymic 7 months after gabapentin
      was added. His Young Mania Rating Scale (YMRS) score was 27 when gabapentin was
      added, 9 after 1 month, 15 after 4 months, and 6 after 7 months. Controlled
      studies are needed to evaluate the possible anti-manic, mood stabilizing, and/or
      anti-depressant properties of gabapentin in youth.

PMID- 9639084
TI  - Sialic acid-binding lectin with antibacterial activity from the horse mussel:
      further characterization and immunolocalization.
AB  - A heterogeneous sialic acid-binding lectin with affinity for bacterial LPS was
      isolated and partially characterized from hemolymph of the horse mussel Modiolus
      modiolus.(1) Using two-dimensional electrophoresis with immobilized pH gradients,
      the lectin revealed three subunits with different molecular weight and
      isoelectric points (pI); Mr14 (pI approximately 5.1 and approximately 5.5), 17.5
      (pI approximately 5.5) and 20 (pI approximately 4.9) kDa. The affinity purified
      lectin existed in its native state as aggregates, and by stepwise centrifugation
      it could be fractionated into molecular entities with distinct specificities
      towards human and/or horse erythrocytes (modiolin H and/or E activity,
      respectively). While the medium size entities (range < or = 30 and < 100 kDa)
      exhibited only modiolin E activity and the lowest size entities (range < or = 5
      and < 10 kDa) demonstrated only modiolin H activity, the largest aggregates (> or
      = 100 kDa-)expressed both activities. Antibacterial activity of the lectin has
      been observed against various marine bacteria, whereas the whole hemolymph was
      less effective. The lectin exhibited strong antibacterial effect against all
      tested strains of Vibrio anguillarum, Vibrio salmonicida, Vibrio viscosus, Vibrio
      wodanis, and Vibrio ordalii, slight effect on Aeromonas salmonicida salmonicida
      and Shewanella putrefaciens, and no inhibitory effect with Alteromonas sp.
      Hemolymph of the horse mussel demonstrated no antibacterial effect against A.
      salmonicida salmonicida, Alteromonas sp., Sh. putrefaciens and some strains of V.
      anguillarum, but slight effects against some strains of V. anguillarum and both
      strains of V. ordalii, and more predominantly against V. wodanis, V. salmonicida
      and V. viscosus. These results indicate that the lectin plays a role in
      elimination of bacteria. Circulating hemocytes were demonstrated to be the source
      of the lectins since granules of the hemocytes were immunoreactive to anti
      hemolymph lectin antibody and protein A/gold labelling.

PMID- 9639085
TI  - Differential production of active oxygen species in photo-symbiotic and non
      symbiotic bivalves.
AB  - We investigated the generation of active oxygen species in the bivalves,
      Crassostrea gigas, Fulvia mutica and Tridacna crocea in order to understand the
      defensive mechanisms in giant clams that allow a stable association with
      symbiotic zooxanthellae. C. gigas produced active oxygens, superoxide anion and
      nitric oxide upon stimulation by phorbol myristate acetate. F. mutica generated a
      little amount of superoxide anion and nitric oxide, and contained significant
      phenoloxidase activity which catalyzes formation of quinones. T. crocea did not
      generate any apparent active oxygen species or quinones. The importance of
      lacking rapid cytotoxic responses consisting of active oxygen species to foreign
      organisms in the symbiotic clam is discussed.

PMID- 9639086
TI  - Evidence for antigen recognition by nonspecific cytotoxic cells: initiation of 3H
      thymidine uptake following stimulation by a protozoan parasite and homologous
      cognate synthetic peptide.
AB  - Catfish nonspecific cytotoxic cells bind to and lyse certain protozoan parasites
      and tumor cells. Target cell binding is facilitated by recognition of (minimally)
      one antigenic determinant. Binding to this determinant initiates multiple
      signalling pathways in NCC including protooncogene kinase phosphorylation,
      regulation of phosphatase activity and increased membrane receptor expression. In
      the present study, highly purified NCC were activated in vitro with the protozoan
      parasite Tetrahymena pyriformis, with a multiple antigenic peptide (MAP) composed
      of the cognate antigenic determinant of this parasite (i.e. natural killer target
      antigen/NKTag) and NCC were activated with a monoclonal antibody specific for the
      NCC receptor which binds NKTag. NCC were purified by Percoll density gradients
      and negative selection by panning (2x) over anti-sIg specific mab 9E1. In 5 day
      proliferation experiments, treatment of NCC with immobilized Tetrahymena
      initiated a significant increase in uptake of tritiated thymidine. This appeared
      to be a primary response in that NCC from in vivo parasite primed catfish did not
      have secondary-like proliferation responses. Stimulation of NCC with immobilized
      synthetic peptides composed of the cognate antigenic determinant of this parasite
      (i.e. MAP) also caused significant increased uptake of tritiated thymidine. An
      indication that NCC recognize a specific antigenic determinant was that sMAP
      (i.e. peptides composed of the same amino acids as MAP but in a scrambled
      sequence) failed to increase incorporation. Similar to the MAP results, mab 5C6
      binding to NCC also caused increased thymidine uptake. To determine if an IL-2
      cosignal was required to achieve optimum activation responses by NCC, different
      concentrations of human recombinant IL-2 (rHuIL-2) were tested individually or as
      costimulants. Co-treatment of NCC with rHuIL-2 and any of the three stimuli
      (parasite, MAP, mab 5C6) did not produce increased proliferation of NCC. These
      studies demonstrated that NCC specifically recognize an antigenic determinant on
      protozoan parasites and binding to this antigen produces an activation signal
      that may have important consequences for elicitation of innate immunity.

PMID- 9639087
TI  - Intracellular signaling events in superoxide generation and adhesion of channel
      catfish, Ictalurus punctatus rafinesque, neutrophils to the extracellular matrix
      protein fibrinogen.
AB  - Activation of channel catfish neutrophils is essential if these cells are to
      participate in adhesion to extracellular matrix proteins or generate
      intracellular superoxide for killing of microbes. Various signaling pathways are
      required for these activities to occur. The objective of this study was to
      identify components of the signal transduction pathways in channel catfish
      neutrophils. A23187, bryostatin, and phorbol dibutyrate (PDBU) all induced
      catfish neutrophil adhesion to fibrinogen coated plates and the adhesion could be
      significantly reduced when neutrophils were pretreated with staurosporine (1 x
      10(-7) M). Staurosporine was the only inhibitor used in the study that inhibited
      or reduced PDBU-induced adhesion of catfish neutrophils to fibrinogen. Phorbol
      dibutyrate at the concentrations used in the adhesion assay was the only
      stimulant that caused generation of intracellular superoxide and therefore was
      the only stimulant used in the remainder of the study. Aristolochic acid (1 x 10(
      4) and 3 x 10(-5) M) + PDBU and staurosporine (1 x 10(-7) and 1 x 10(-8) M) +
      PDBU caused a significant decrease (p < or = 0.05) in PDBU-induced intracellular
      oxygen generation. The role of protein kinase C and phospholipases in channel
      catfish neutrophil adhesion and superoxide generation are discussed.

PMID- 9639088
TI  - A comparative study of pentraxin-like proteins in different fish species.
AB  - Pentraxins are a family of pentameric serum proteins that have been conserved in
      evolution and share sequence homology, similar subunit assembly and the capacity
      for calcium-dependent ligand binding. The classical pentraxins are human C
      reactive protein (CRP) and serum amyloid P component (SAP). The sequence homology
      and gene organization indicate that they arose from a gene duplication of an
      ancestral pentraxin gene. They are usually isolated based on their affinity for
      phosphorylcholine and agarose, respectively. We have used this method for
      isolation of pentraxin-like proteins from normal serum of Atlantic salmon (Salmo
      salar), common wolffish (Anarhichas lupus), cod (Gadus morhua) and halibut
      (Hippoglossus hippoglossus). Although pentraxin structures have not been
      verified, the isolated proteins all appear to be pentraxin-like based on their
      binding specificity, molecular weight of subunits, cross-reactivity with
      antibodies to human pentraxins and N-terminal amino acid sequences. However, with
      the described method only one pentraxin-like protein was detected in each of the
      fish species.

PMID- 9639089
TI  - In vitro cell-mediated cytotoxicity against allogeneic erythrocytes in ginbuna
      crucian carp and goldfish using a non-radioactive assay.
AB  - Cell-mediated cytotoxicity of clonal ginbuna crucian carp leukocytes against
      allogeneic erythrocytes is described using a sensitive non-radioactive in vitro
      assay. Hemoglobin released from target erythrocytes after cell-mediated
      erythrolysis was detected by tetramethylbenzidine (TMB). TMB assay showed clear
      correlation with a 51Cr-release assay and even exhibited higher cytotoxicity. The
      use of erythrocytes as target cells has several advantages over a conventional
      51Cr-release assay. Erythrocytes do not have cytotoxic activity, are relatively
      homogeneous, are available in large numbers and erythrocyte donors need not be
      killed. Leukocytes from fish sensitized by erythrocyte injection or scale
      grafting efficiently lysed allogeneic erythrocytes, but did not kill isogeneic or
      autologous erythrocytes. In contrast, leukocytes from unsensitized fish did not
      lyse allogeneic erythrocytes and repeated sensitizations by allogeneic grafts
      were necessary to induce cytotoxic cells. Effector cells isolated from peripheral
      blood showed a higher cytotoxic effect toward allogeneic target cells than
      effector cells isolated from kidney. These studies support the hypothesis that
      fish are capable of a genetically restricted specific cell-mediated cytotoxicity.

PMID- 9639090
TI  - Isolation and initial characterisation of complement components C3 and C4 of the
      nurse shark and the channel catfish.
AB  - Complement components C3 and C4 have been isolated from the serum of the nurse
      shark (Ginglymostoma cirratum) and of the channel catfish (Ictalurus punctatus).
      As in the higher vertebrates, the fish C4 proteins have three-chain structures
      while the C3 proteins have two-chain structures. All four proteins have intra
      chain thioesters located within their highest molecular mass polypeptides. N
      terminal sequence analysis of the polypeptides has confirmed the identity of the
      proteins. In all cases except the catfish C3 alpha-chain, which appears to have a
      blocked N-terminus, sequence similarities are apparent in comparisons with the
      chains of C3 and C4 from higher vertebrates. We have confirmed that the
      activity/protein previously designated C2n is the nurse shark analogue of
      mammalian C4. This is the first report of structural evidence for C4 in both the
      bony and cartilaginous fish.

PMID- 9639091
TI  - Natural cytotoxicity towards allogeneic tumour targets in Xenopus mediated by
      diverse splenocyte populations.
AB  - We have recently demonstrated NK-like activity in the spleen of the clawed frog,
      Xenopus laevis. This paper investigates the cellular basis of this natural
      cytotoxicity. Significant levels of cytotoxicity towards B3B7 allogeneic thymus
      tumour targets, that express neither class Ia nor class II MHC proteins, occurred
      after splenocytes from either control or early-thymectomized (Tx) year-old
      Xenopus were cultured for 48 hours. Killing by Tx cells required their culture in
      growth factor-rich medium (GFM) obtained from concanavalin A-stimulated cells.
      Immunomagnetic cell sorting revealed that cytotoxic effectors in both control and
      Tx frogs were found in the B cell-depleted population, but never in the B cell
      enriched fraction. Splenocytes from control Xenopus, depleted of T cells by
      magnetic sorting and following culture in GFM, also developed natural
      cytotoxicity towards allotumour cells. Magnetic cell sorting also revealed that
      purified (CD5+) T cells cultured for 48 hours in GFM also became able to lyse the
      allogeneic tumour targets. Cytotoxicity mediated by T cells resided not only in
      the CD5+, CD8+ population, but also in the CD5+, CD8- (putative CD4+) T cell
      subset. Ontogenetic studies revealed that splenocytes from 6-7 week-old (stage 56
      57) control larvae, even after 48 hr culture in GFM, were unable to spontaneously
      lyse the allotumour targets, whereas cultured splenocytes from 6 month old
      froglets were effective killers. Thymocytes from larvae or adults routinely
      failed to kill tumour cells. The work highlights the need to use Tx Xenopus to
      further explore non-T-cell-mediated, NK-like cytotoxicity at the amphibian level
      of evolution.

PMID- 9639092
TI  - The complement system of the marsupial Monodelphis domestica.
AB  - The activation requirements and pathways of the serum C' system of the marsupial
      Monodelphis domestica were characterized using standard hemolytic procedures. The
      existence of distinct classical and alternative activation pathways was
      established on the basis of their ionic requirements, hemolytic capacity at
      different temperatures, kinetics of hemolysis, and differential susceptibility to
      the classical pathway inhibitor carrageenan. For the most part, the activities of
      these pathways were influenced by factors and conditions in a manner similar to
      the way they affect the activity of eutherian complement. These observations
      provide further support for the idea that Monodelphis domestica would serve as a
      useful model for comparative immunological studies in mammals.

PMID- 9639093
TI  - Age-dependent remodeling of peripheral blood CD4+ CD8+ T lymphocytes in
      cynomolgus monkeys.
AB  - Recently, we have found in adult cynomolgus monkeys that substantial peripheral
      blood CD4+ CD8+ double-positive (DP) T lymphocytes exhibit a resting memory
      phenotype and increase in proportion with age. In this study, we investigated
      whether phenotypic changes occur in the course of the increase in proportion of
      the DP T cells. The results obtained from 195 clinically healthy monkeys aged
      from 1 month to 31 years showed that the CD29hi and CD28 subpopulation in the DP
      T subset increased in proportion with age and that the increase reached a plateau
      at six years old for the CD29hi subpopulation and at eleven years old for the
      CD28 one, respectively. The phenotypic alteration preceded the abrupt increase in
      proportion of the DP T cells and was able to be classified into four phases on
      the basis of the qualitative and quantitative alteration.

PMID- 9639094
TI  - LAMP-1/ESGp appears on the cell surface of single celled mouse embryos subsequent
      to fertilization.

PMID- 9639095
TI  - Validation of routine mycoplasma testing by PCR.

PMID- 9639096
TI  - A clonal chondrocytic cell line derived from BMP-2/T antigen-expressing
      transgenic mouse.

PMID- 9639097
TI  - Primary human vascular smooth muscle cell culture enhanced by human umbilical
      cord serum.

PMID- 9639098
TI  - Establishment of monk seal cell lines.

PMID- 9639099
TI  - Culture and characterization of sinusoidal endothelial cells isolated from human
      liver.
AB  - Although most vascular models use large vessel endothelial cells from human
      umbilical veins, there is marked heterogeneity among endothelial cells from
      different vascular beds and organs. More accurate modeling of endothelial
      involvement in liver diseases, including metastasis, may result from the use of
      human hepatic sinusoidal endothelial cells. Liver resection specimens were
      sectioned, then treated with a 1.2 U/ml dispase solution. The tissue slurry was
      mechanically disaggregated and separated by centrifugation on a Percoll density
      gradient. Cells were then cultured in an endothelial-specific media with growth
      factors. These techniques resulted in a homogeneous monolayer consistent with
      endothelial cells by light microscopy. An endothelial origin was further
      confirmed by the expression of Factor VIII, binding of Ulex lectin, and uptake of
      acetylated low density lipoprotein. Electron microscopy showed transcellular
      fenestrations consistent with a sinusoidal origin. These human hepatic sinusoidal
      endothelial cells were then studied for expression of the adhesion molecules
      CD31/PECAM, CD34, E-selectin, ICAM-1, L-selectin, LFA-3, P-selectin, and VCAM-1
      plus the binding of wheat germ agglutinin lectin. The patterns of adhesion
      molecule expression and lectin binding by these cells are characteristic of
      hepatic sinusoidal endothelia. In this paper, we have described a method for
      isolation and culture of human cells with the morphologic and phenotypic
      characteristics of hepatic sinusoidal endothelia.

PMID- 9639101
TI  - The proliferation of mouse mammary epithelial cells in response to specific
      mitogens is modulated by the mammary fat pad in vitro.
AB  - The ability of the murine mammary fat pad to directly stimulate the growth of
      mammary epithelial cells and to modulate the effects of various mammogenic agents
      has been investigated in a newly described, hormone- and serum-free coculture
      system. COMMA-1D mouse mammary epithelial cells were cultured for 5 or 7 d with
      various supplements in the absence or presence of epithelium-free mammary fat pad
      explants from virgin female BALB/c mice. Cocultured fat pad stimulated increases
      in the DNA content of COMMA-1D cultures by two- to threefold or six- to eightfold
      after 5 or 7 d, respectively. The mitogenic effect was additive to that of 10%
      fetal calf serum and could not be attributed to the release of prostaglandin E2
      or synthesis of prostaglandins by epithelial cells. In addition, bovine serum
      albumin attenuated (P < 0.05) the mitogenic effect of cocultured mammary fat pad.
      Added alone, insulinlike growth factor-I, epidermal growth factor, and insulin
      increased (P < 0.05) total DNA of COMMA-1D cultures by 2.5-, 3.7-, and 2.3-fold,
      respectively. Cocultured mammary fat pad markedly interacted (P < 0.01) with
      these mitogens to yield final DNA values that were 21.2-, 13.3-, and 22.1-fold
      greater than in basal medium only. Associated with this proliferation was the
      formation of numerous domes above the COMMA-1D monolayer. There was no
      proliferative response to growth hormone or prolactin in the absence or presence
      of cocultured fat pad (P > 0.05). Whereas hydrocortisone did not alter cell
      number, it attenuated (P < 0.05) the mitogenic effect of cocultured mammary fat
      pad. These results indicate that the murine mammary fat pad is not only a direct
      source of mitogenic activity, but also modulates the response of mammary
      epithelial cells to certain mammogens.

PMID- 9639100
TI  - Cytokine inducible matrix metalloproteinase expression in immortalized rat
      chondrocytes is independent of nitric oxide stimulation.
AB  - The objective of this study was to determine if an immortalized mammalian
      chondrocyte cell line had a profile of matrix metalloproteinase (MMP) expression
      that was consistent with what has been reported for primary chondrocytes in vitro
      and in vivo. A combination of zymography, Western, and Northern analysis was used
      to examine the expression of MMPs that are relevant to cartilage degradation.
      Both interleukin-1beta and tumor necrosis factor alpha induced a 4- to 9-fold
      increase in the level of MMP-9 expression in conditioned media, and a 17- to 24
      fold increase in MMP-3 mRNA. Other compounds such as basic fibroblast growth
      factor and staurosporine each increased MMP-9 expression individually and
      potentiated the effects of the two cytokines. Transforming growth factor beta had
      no positive or inhibitory effects. N-methyl arginine blocked the increase in
      nitric oxide observed following treatment with the cytokines but did not prevent
      the increased expression of MMPs. The pattern of metalloproteinase expression
      observed in IRC cells and the response to cytokines is very similar to what has
      been reported during the pathogenesis of osteoarthritis. The IRC cells should be
      useful as a model system to study basic mechanisms controlling chondrocyte MMP
      expression and to identify pharmacological modulators of this process.

PMID- 9639102
TI  - Ultrastructural and functional study of the liver pigment cells from Rana
      esculenta L.
AB  - A study of the liver pigment cells of Rana esculenta L. has been performed on
      both liver in toto and cells in culture. Ultrastructural and cytochemical
      analyses showed a close relationship between this visceral pigment cell system
      and the cells of hepatic macrophage lineage. Like the latter, the liver pigment
      cells present phagocytic activity, in the sinusoids and in vitro, and give a
      positive response to tests for peroxidase and lipase. The liver pigment cells are
      isolated, together with the Kupffer cells, from the sinusoidal cell fraction of
      the liver. In culture, they maintain their melanogenetic ability, demonstrated by
      the presence of dopaoxidase activity in the soluble, membranous, and melanosome
      fractions. Analysis of the cultures showed that as culture time increased, so did
      melanosome dopaoxidase activity, the number of pigmented fields, and the level of
      pigmentation of the cells. The values of dopaoxidase activity of the pigment
      cells in culture show the same seasonal oscillations as the system in toto,
      indicating that the cells maintain an internal clock, at least in the first 72 h
      of culture. There is evidence that the pigment cells are macrophages which can
      express a melanogenetic function. Our results and other experimental data provide
      a basis for hypothesizing that the pigment cells in Rana esculenta L. liver may
      derive from, or have a common origin with, the Kupffer cells.

PMID- 9639103
TI  - Direct cloning of astrocytes from primary culture without previous
      immortalization.
AB  - In primary cultures, much evidence shows the existence of different subtypes of
      astrocytes that are not all identified. One methodology for studying these
      subtypes can be their cloning. The present investigation shows a method for a
      direct cloning of astrocytes without previous immortalization. Astrocytes from
      the cerebral cortex of newborn rats were cultured, purified by shaking, and
      harvested by trypsinization. One single astrocyte was plated in a small volume of
      a homemade cloning medium. After getting a colony, successive platings were made
      using larger and larger vessels, up to 60-mm-diameter petri dishes. Then,
      subcultures were made. The yield of the cloning was similar to that of common
      eukaryotic cell clonings. All along the cloning procedure, the cells were
      positively immunostained with anti-glial fibrillary acidic protein antibodies.
      Cloned cells from some batches were spindle-shaped, looking like fibroblasts.
      Nevertheless, they were immunostained with anti-glial fibrillary acidic protein
      antibodies, unlike true fibroblasts. These spindle-shaped astrocytes were
      compared to cells from an astrocytoma cell line that had the same shape. The
      growth pattern of the astrocytoma cells was different from that of the astrocytes
      cloned from the primary cultures. All the types of studied cells contained
      glycogen. On the basis of the criteria of morphology, of glial fibrillary acidic
      protein immunolabeling, and of glycogen synthesis, the cloned cells kept the
      characteristics of astrocytes. This study shows that it is perfectly possible to
      get clones of astrocytes from one astrocyte without previous immortalization,
      giving thus a convenient material for the study of astrocyte biology.

PMID- 9639105
TI  - An in vitro approach for the characterization of the cycling B cell response.
AB  - Because isolation of sufficient numbers of cycling, germinal center B cells from
      mice for biochemical characterization of BCR-derived signals can be problematic,
      we have designed an experimental approach for generating large numbers of cycling
      B cells for further study. In the experiments reported here, small, resting B
      cells were polyclonally stimulated with lipopolysaccharide (LPS), and cycling B
      cells isolated as two bands on three-step Percoll gradients. Cycling B cells
      isolated at Days 2, 4, or 6 of preactivation showed an increased expression of
      Fas receptor and peanut agglutinin binding, with a concomitant decrease in sIgD
      positivity. These cells phenotypically resembled extrafollicular or early
      germinal center B cells. These cycling B cells were used to study the functional
      consequences of differential signaling through the BCR. Strong cross-linking of
      BCR, by restimulation of cycling normal B cells with either immobilized or
      soluble F(ab')2 anti-mu and cycling hen egg lysozyme (HEL) transgenic B cells
      with either soluble or immobilized HEL, extended cellular proliferation by 2-3 d.
      In contrast, cycling B cells either restimulated with soluble, whole anti-mu (to
      mimic binding of soluble immune complexes) or cultured in the absence of
      restimulation (to mimic cycling B cells not competitive for antigen) resulted in
      the rapid exit of the cells from cycle. This system will enable the molecular and
      biochemical characterization of signal delivery to cycling B cells.

PMID- 9639104
TI  - Autocrine secretion of TGF-beta 1 and TGF-beta 2 by pre-adipocytes and
      adipocytes: a potent negative regulator of adipocyte differentiation and
      proliferation of mammary carcinoma cells.
AB  - We have developed an in vitro system to examine the influence of adipocytes, a
      major mammary stromal cell type, on the growth of a murine mammary carcinoma,
      SP1. Previously, we have shown that 3T3-L1 adipocytes release a mitogenic factor,
      hepatocyte growth factor, which strongly stimulates proliferation of SP1 cells.
      We now show that 3T3-L1 pre-adipocytes secrete active inhibitory molecules which
      inhibit DNA synthesis in SP1 cells. In addition, latent inhibitory activity is
      present in conditioned media (CM) from both pre-adipocytes and adipocytes, and is
      activated following acid treatment. CM also inhibited DNA synthesis in Mv1Lu wild
      type epithelial cells, but not DR27 mutant epithelial cells which lack TGF-beta
      type II receptor. Inhibitory activity of CMs was partially abrogated by
      neutralizing anti-TGF-beta1 and anti-TGF-beta2 antibodies, and was removed
      following ultrafiltration through membranes of 10,000 Mr but not 30,000 Mr pore
      size. These results show that the inhibitory effect on DNA synthesis is mediated
      by TGF-beta1-like and TGF-beta2-like molecules. In addition, acid-treated CM as
      well as purified TGF-beta inhibited differentiation of pre-adipocytes. Untreated
      pre-adipocyte CM, but not mature adipocyte CM, spontaneously inhibited adipocyte
      differentiation. Together, these findings indicate that pre-adipocytes
      spontaneously activate their own secreted TGF-beta, whereas mature adipocytes do
      not, and suggest that activation of TGF-beta has a potent negative regulatory
      effect on adipocyte differentiation and tumor growth. Thus, TGF-beta may be an
      important modulator of tumor growth and adipocyte differentiation via both
      paracrine and autocrine mechanisms. These findings emphasize the importance of
      adipocyte-tumor interactions in the regulation of tumor microenvironment.

PMID- 9639106
TI  - Chlorophyll and pheophytin derivatives in geochemical transformation pathways: a
      surface-enhanced resonance Raman spectroscopic study.
AB  - Protected surface-enhanced resonance Raman spectroscopy (PSERRS) has been used to
      study a number of chlorophyll transformation products that have been suggested as
      intermediates in the so-called Treibs hypothesis which describes the
      transformation of ancient chlorophyll a (chl a) in the biosphere into
      desoxophylloerythroetio-porphyrin (DPEP) found in sedimentary environments. Both
      Soret- and Qy-resonant PSERR spectra have been recorded, providing two
      dimensional structural fingerprints containing a number of bands which enable the
      presence of specific peripheral substituents to be identified. Some of these
      marker bands can be assigned directly to vibrational modes of the particular
      substituents. This has allowed further characterization of the vibrational
      spectrum of chl a; in particular, a vinyl mode has been identified which
      previously was thought to be Raman silent.

PMID- 9639107
TI  - Effect of surface modifiers on the electrode reactions and conformation of
      cytochrome c3 adsorbed on a silver electrode.
AB  - Surface-enhanced resonance Raman scattering and electroreflectance voltammetry
      were used to investigate the effect of electrode surface modification on the
      structure and redox properties of cytochrome c3 immobilized on Ag surfaces. It is
      shown that the redox reactions of cytochrome c3 are more reversible at an 11
      mercaptoundecanoic acid modified Ag electrode as compared to a bare metal
      surface. The heme of cytochrome c3 is in a mixed low and high spin state when
      adsorbed at the bare electrode, whereas only the low spin form is present on the
      11-mercaptoundecanoic acid modified electrode, suggesting that the native
      conformation is maintained in the latter case. The reduction potential is close
      to that of the most positive macroscopic potential as determined by
      electroreflectance spectroscopy. In contrast, the reduction potential as
      determined by SERRS undergoes a large positive shift in the presence of 4,4'
      bipyridine, the magnitude of which is dependent upon the concentration of 4,4'
      bipyridine. These results indicate that the effect of the cytochrome c3
      interaction with the 4,4'-bipyridine-modified surface is significantly different
      as compared to its interaction with the 11-mercaptoundecaodoic acid modified
      surface. Moreover, the results emphasize that electrode modifiers can have
      dramatically different effects on the redox properties of different proteins. It
      is well known that 4,4'-bipyridine acts as a redox promoter in the case of
      cytochrome c, whereas no electrochemical or electroreflectance response was
      observed in the case of cytochrome c3.

PMID- 9639108
TI  - Raman linear intensity difference of membrane-bound peptides: indole ring
      orientations of tryptophans 11 and 13 in the gramicidin A transmembrane channel.
AB  - A Raman linear intensity difference (RLID) method has been developed to determine
      orientations of chromophores in membrane-bound peptides and proteins. The method
      involves orientation of the peptide or protein in lipid bilayer membranes and
      measurement of intensity differences between Raman spectra excited with two
      orthogonal laser polarizations. Analysis of the RLID spectrum is simplified when
      the chromophore exhibits a vibrational mode for which the Raman band is enhanced
      through resonance with a single molecular electronic transition. To examine the
      indole ring orientations of Trp residues in the gramicidin A transmembrane
      channel, we have prepared analogues of gramicidin A, in which one of four Trp
      residues is replaced by deuterated Trp (Trp-2,4,5,6,7-d5). Two vibrational Raman
      bands omega(d)3 and omega(d)2 of deuterated Trp have been shown to gain intensity
      predominantly through resonance with the Bb and La electronic transitions,
      respectively, when excited at 244 and 257 nm. By examining the RLID spectra of
      the omega(d)3 and omega(d)2 bands of gramicidin A channels oriented in
      phospholipid bilayer membranes, we have determined the inclination angles of the
      Bb and La transition moments with respect to the channel axis in the absence and
      presence of Na+. The orientations of the Trp-11 and Trp-13 indole rings in the
      gramicidin channel structure have been derived from the inclination angles of the
      transition moments. The indole rings of Trp-11 and Trp-13, which are known to
      shift along the channel axis upon binding of Na+, do not reorient during their
      positional shifts.

PMID- 9639109
TI  - A spectroscopic study of the hydrogen bonding and pi-pi stacking interactions of
      harmane with quinoline.
AB  - A spectroscopic (UV-vis, Fourier transform IR, steady state, and time-resolved
      fluorescence) study of the interactions of the ground and excited singlet states
      of harmane (1-methyl-9H-pyrido/3,4-b/indole) with quinoline has been carried out
      in cyclohexane, toluene, and buffered pH=8.7 aqueous solutions. To analyze how
      the number of rings in the substrate influences these interactions, pyridine and
      phenanthridine have also been included in this study. In cyclohexane and toluene
      1:1 stoichiometric hydrogen-bonded complexes are formed in both the ground and
      the excited singlet states. As the number of rings of the benzopyridines and the
      solvent polarity increase hydrogen-bonding interactions weaken and pi-pi van der
      Waals interactions become apparent.

PMID- 9639110
TI  - The binding of biotin analogues by streptavidin: a Raman spectroscopic study.
AB  - Raman spectra of anhydrous complexes of streptavidin (Strep) with biotin (Bio)
      and some Bio analogues [Biotin methyl ester (MEBio), desthiobiotin (DEBio), 2'
      iminobiotin (IMBio), and diaminobiotin (DABio)] were recorded. The vibrational
      results indicate that the interaction with some of these ligands is able to
      modify the overall structure of the protein and this binding results in a
      decrease in the beta-sheet content and an increase in the alpha-helix content. To
      further confirm the conformational changes of the protein structure due to Bio
      analogue binding, the curve-fitting analysis of the amide I Raman band of neat
      Strep and of the complexes were performed. The intensity ratio of the components
      due to the beta-sheet and alpha-helix conformations decreased in the Strep-MEBio,
      Strep-IMBio (pH 11), and Strep-Bio systems, whereas in all the other systems the
      changes were not significant. This behavior differs from that of Avi bound to the
      same ligands and suggests that Strep and Avi differ in their binding selectivity.
      A good correlation was found between the secondary structure percentages of the
      Avi and of the Strep complexes and deltaG(o). On the basis of this linear
      relationship, the vibrational results allow for an acceptable evaluation of the
      dissociation constants of the Strep complexes, not previously reported in the
      literature. The present results indicate a correlation between the type of
      interaction and the effects of the protein-substrate bonding on the overall
      structure of the proteins. The amino acid residues in the binding site appear to
      be positioned in a such a way as to provide a precise fit of Bio. Even slight
      change in the substrate structure causes a weakness in the strength of the
      binding. The vibrational results confirm that both the imidazolidinone and the
      thiophan rings are important in the Strep-Bio interactions, but the former is
      more responsible for the high affinity of the binding. One of the Tyr residues is
      hydrogen bound with the ureido ring and another Tyr could be involved in the
      binding pocket. Trp residues do not directly bind the ligand and probably
      stabilize other binding site residues which in turn interact directly with Bio.

PMID- 9639111
TI  - Pressure-induced structural rearrangements of bovine pancreatic trypsin inhibitor
      studied by FTIR spectroscopy.
AB  - Fourier transform infrared (FTIR) spectroscopy combined with resolution
      enhancement techniques, second-derivative and difference spectroscopies, have
      been used to characterize pressure-induced changes in the structural
      rearrangements of bovine pancreatic trypsin inhibitor (BPTI) in D2O solution at
      25.0 degrees C. According to the observed changes in the amide I' band up to 550
      MPa, the secondary structure elements of BPTI, such as the alpha-helix, 3(10)
      helix, beta-sheet, and beta-turn, are scarcely rearranged except for the loop
      structure of residues of 9-17 and 36-43. The polypeptide backbone is not
      extensively unfolded up to 550 MPa. The minor pressure-induced structural
      rearrangements are completely reversible. A further increase in pressure above
      1000 MPa associated with the precipitation of BPTI in D2O buffer solution induces
      the partial structural rearrangements of the alpha-helix, beta-turn and/or 3(10)
      helix, and beta-sheet. The polypeptide backbone of BPTI is not fully unfolded
      even above 1000 MPa. Most of the protected backbone amide protons involved in the
      beta-sheet remain intact in the pressure range where BPTI is not precipitated,
      while those involved in the alpha-helix and beta-turn and/or 3(10)-helix are
      exchanged with solvent deuterons. The protected backbone amide protons located
      near the surface regions are more easily exchanged with solvent deuterons by
      application of high pressure than those involved in the core.

PMID- 9639112
TI  - Why classify basal cell carcinomas?
AB  - Basal cell carcinoma of the skin is the commonest form of cancer in the white
      population. A simple pathological classification is presented and recommended for
      general use to aid clinicians in their management of cases. Basal cell carcinoma
      can be classified as nodular, infiltrative, superficial apparently multifocal and
      mixed in terms of the histological growth pattern. These patterns can be related
      to the likelihood of complete excision and, if excision is incomplete, to the
      frequency of recurrence.

PMID- 9639113
TI  - Ki67 expression in lichen sclerosus of vulva in patients with and without
      associated squamous cell carcinoma.
AB  - AIMS: To investigate the malignant potential of lichen sclerosus, a study using
      the cell proliferation marker Ki67 comparing lichen sclerosus with and without
      associated squamous cell carcinoma was performed. METHODS AND RESULTS: Formalin
      fixed, paraffin-embedded slides of 13 cases of lichen sclerosus with associated
      carcinoma, and 31 cases without associated carcinoma, including 16 random cases,
      seven with epidermal thickening and eight with epidermal thinning, were examined
      by the immunoperoxidase technique for Ki67, a cell proliferation marker. Ki67
      reactivity was mostly seen in the basal and parabasal cells in both groups of
      lichen sclerosus and this pattern was similar to normal skin, squamous cell
      hyperplasia and analogous to that of one form of squamous cell carcinoma. There
      was a mean of 50 Ki67 positive cells per 100 basal cells in lichen sclerosus with
      associated squamous cell carcinoma; however, in squamous cell hyperplasia
      adjacent to carcinoma this rose to 90 Ki67 positive cells per 100 basal cells. In
      lichen sclerosus without associated carcinoma, the random cases had a count of 53
      per 100 basal cells, those with epidermal thickening 53 and those with thinning
      42. Non-genital normal skin had a count of 71 per 100 basal cells. CONCLUSION:
      The lack of qualitative differences of Ki67 expression in normal skin, in lichen
      sclerosus with and without carcinoma, in squamous cell hyperplasia and in one
      form of squamous cell carcinoma indicates that these conditions share a common
      localized pattern of cell proliferation and does not support or deny the
      malignant potential of lichen sclerosus. The higher Ki67 count in squamous cell
      hyperplasia adjacent to carcinoma could indicate premalignancy or a reaction to
      the carcinoma. In patients without carcinoma, the higher Ki67 count in thickened
      lichen sclerosus compared to thinned suggests that some or all of the cases of
      thickened lichen sclerosus were lichen sclerosus with squamous cell hyperplasia
      or that lichen simplex chronicus superimposed on lichen sclerosus has a higher
      Ki67 expression or that the distinction between squamous cell hyperplasia and
      lichen simplex chronicus is only one of terminology.

PMID- 9639114
TI  - Nerve sheath tumours with hybrid features of neurofibroma and schwannoma: a
      conceptual challenge.
AB  - AIMS: To characterize and delineate a subset of rare nerve sheath tumours showing
      hybrid features of neurofibroma and schwannoma. METHODS AND RESULTS: Nine lesions
      were identified in the authors' files showing predominant features of
      neurofibroma with distinct, often nodular regions of classical schwannomatous
      differentiation. Most patients were adults, eight out of nine were male. Of the
      nine lesions, two were dermal, two were subcutaneous and five were subfascial.
      Five lesions had a plexiform architecture and one patient had overt
      neurofibromatosis. One out of six patients with follow-up developed local
      recurrence. Schwannoma-like regions displayed strong S100 staining, in contrast
      to more varied and limited S100 reactivity in neurofibromatous areas. The Antoni
      A areas could be quite cellular with high MIB-1 proliferation indices. No lesion
      underwent malignant change. CONCLUSIONS: Our results demonstrate that some nerve
      sheath tumours may contain histologically clear components of both neurofibroma
      and schwannoma, suggesting that (despite evident and well-defined
      clinicopathological differences) these two lesions may be even more closely
      related than previously recognized. Whether this phenomenon results from a
      localized microenvironmental change or from a clonal genetic alteration remains
      unknown.

PMID- 9639115
TI  - Vascular endothelial cadherin is expressed by perineurial cells of peripheral
      nerve.
AB  - AIMS: To study the distribution of vascular endothelial (VE) cadherin in
      peripheral nerves. METHODS AND RESULTS: Using two monoclonal antibodies that
      detect VE-cadherin (TEA1.31 and 7B4) an immunohistochemical study of VE-cadherin
      expression in five common peroneal nerve biopsies and five skin specimens
      containing small peripheal nerves was performed. VE-cadherin was consistently
      expressed by the perineurium of nerves but not by other nerve elements such as
      Schwann cells or axons. CONCLUSION: This report indicates that VE-cadherin is
      not. as was previously thought, a specific marker of endothelial cells and
      further defines the phenotype of the perineurial cell. The established role of VE
      cadherin in controlling the permeability of vascular endothelium suggests that
      this molecule may have a similar role in the perineurium. VE-cadherin may
      therefore be important in the maintenance of the blood-nerve barrier, the
      peripheral nerve equivalent of the blood-brain barrier.

PMID- 9639116
TI  - Cellular 'neurothekeoma': an epithelioid variant of dermatofibroma?
AB  - AIMS: Cellular neurothekeoma is a rare benign cutaneous neoplasm with conflicting
      opinions regarding its histogenetic origin (nerve sheath, smooth muscle,
      myofibroblasts) as well as its relation to myxoid neurothekeoma (nerve sheath
      myxoma). The present series describes 15 cases whose clinicopathological features
      indicate a relationship to dermatofibroma. METHODS AND RESULTS: In this
      retrospective clinicopathological study, the lesions preferentially occurred in
      adolescents to young adults on the upper half of the body, often clinically
      diagnosed as some kind of fibrohistiocytic tissue response. Besides
      characteristic whorled nests to fascicles of palely eosinophilic epithelioid
      cells, all lesions showed variable clues pointing to dermatofibroma: acanthosis,
      ill-defined storiform periphery, peripherally accentuated prominent sclerosis and
      lymphocytic demarcation/infiltration. Immunohistochemically, all cases were
      positive with NK1C3 (CD57), KiM1p and proliferating cell nuclear antigen, seven
      were positive for neurone specific enolase, five for factor XIIIa, six for smooth
      muscle specific actin and three for E9, an antimetallothionein marker. These
      findings are similar to those of conventional dermatofibromas, the variability of
      the profile being best explained by time cycle and function dependent changes.
      Ultrastructurally, two cases showed microfilaments, attachment plaques, prominent
      pinocytosis and focal remnants of basal lamina. A careful study of the data and
      photomicrographs from the literature reveals that in many cases similar
      conclusions could be reached. Obvious discrepancies are most likely due to the
      confusion with myxoid neurothekeoma, a well circumscribed, more spindly and
      myxoid, S100 positive lesion of Schwannian origin. CONCLUSION: The appearance of
      dermatofibromas is markedly influenced by architectural, e.g. in deep penetrating
      dermatofibroma, and/or cellular/stromal criteria, e.g. in epithelioid cell
      histiocytoma or sclerosing dermatofibroma. Cellular neurothekeoma seems to be a
      variant of dermatofibromas with both architectural and cellular/stromal
      peculiarities, i.e. plexiform pattern, epithelioid cytology and stromal
      sclerosis.

PMID- 9639117
TI  - Solitary fibrous tumour: significance of p53 and CD34 immunoreactivity in its
      malignant transformation.
AB  - AIMS: To clarify the association of p53 and CD34 expression with development of
      malignant solitary fibrous tumour we have studied 10 cases of solitary fibrous
      tumour arising in the pleura, retroperitoneum and pelvic cavity with
      clinicopathological features of malignancy. METHODS AND RESULTS: Tumours were
      localized solid masses with or without necrosis in eight and they nearly totally
      occupied the pleural cavity in two. Basic histology of the tumours was the
      proliferation of spindle cells arranged in 'patternless' pattern or in
      interlacing bundles with nuclear atypia and mitotic activities of various degree.
      In two, high-grade foci were present within low or intermediate-grade tumours.
      Recurrent tumours also showed more atypical features than primary tumours in two.
      Immunohistochemical studies showed CD34 positivity in seven, but three of them
      showed marked diminution or complete loss of CD34 expression in high-grade foci
      or a recurrent tumour. Three high-grade cases showed totally negative staining
      for CD34. p53 was strongly expressed in cases with fatal outcome, clinical
      recurrence, nuclear atypia, high mitotic activity or local invasion, whereas
      almost negative in benign tumours. CONCLUSIONS: Malignant solitary fibrous
      tumours may occur de novo or by transformation within benign or low-grade tumours
      and may be associated with p53 mutation. Although CD34 is a useful marker in the
      diagnosis of solitary fibrous tumour, one should bear in mind that its expression
      can be lost in high-grade tumours.

PMID- 9639118
TI  - Translocation 2;11 in a fibroma of tendon sheath.
AB  - AIMS: To determine whether fibromas of tendon sheath represent a reactive
      fibrosing process or whether they are neoplastic, we investigated the chromosomes
      of the proliferating cells. A clonally occurring karyotypic abnormality would be
      an argument in favour of these fibromas being neoplastic. METHODS AND RESULTS: A
      biopsy specimen of a fibroma of tendon sheath was cultured after collagenase
      exposure leading to dissociation of the tissue. The cultured cells were harvested
      after 4 days and chromosome analysis done according to standard procedures. Ten
      out of 20 karyotyped cells showed an identical chromosome abnormality
      characterized by a t(2;11)(q31-32;q12). The other 10 cells showed a normal 46,XX
      karyotype. CONCLUSION: The clonally occurring chromosome abnormality found in
      this fibroma of tendon sheath suggests that this proliferation is neoplastic and
      not a reactive fibrosing process.

PMID- 9639119
TI  - A cytogenetic approach to the differential diagnosis of metastatic clear cell
      renal carcinoma.
AB  - AIMS: To determine by cytogenetic analysis the origins of two clear cell tumours
      in a 70-year-old Caucasian woman, one in the thyroid gland, and the other in the
      skin, 16 and 20 years, respectively, after tumour nephrectomy. We sought a
      conclusive distinction between primary clear cell thyroid carcinoma and its
      cutaneous metastasis, and between thyroid and cutaneous metastases of clear cell
      renal carcinoma (RCC). METHODS AND RESULTS: Paraffin sections of the previously
      formalin-fixed thyroid tumour, and the fresh cutaneous tumour were stained with
      haematoxylin and eosin (H & E) and periodic acid-Schiff (PAS). Additionally,
      samples of both tumours were examined electron microscopically.
      Immunohistochemistry was performed with antibodies against thyroglobulin,
      pancytokeratin, keratin 7, 8, 18 and 19, chromogranin, calcitonin, CEA, vimentin
      and EMA. Five to six micrometre sections of both tumours were analysed with alpha
      satellite probes of chromosomes 3, 7 and 17 using chromosomal in-situ
      hybridization (CISH). The cutaneous tumour was also cultured and analysed
      cytogenetically. The thyroid tumour displayed some follicle-like structures that
      stained positive with both PAS and antithyroglobulin, giving evidence of possibly
      entrapped thyroid follicles in metastatic RCC. The cutaneous tumour was negative
      for both stains. The tumours were ultrastructurally completely devoid of
      neurosecretory granules. Classical cytogenetical analysis of the cultured
      cutaneous tumour cells revealed monosomies 3 and 14, well-known specific primary
      and secondary aberrations, respectively, in clear cell RCC, and hitherto not
      reported in thyroid carcinomas. CISH of both tumours revealed monosomy 3,
      indicating a cytogenetical correlation between them. There was no evidence of
      typical chromosomal aberrations for thyroid carcinomas like structural changes on
      10q, structural rearrangements or translocations of chromosome 7. CONCLUSION:
      Although neither histological sections, nor paraffin blocks of the original
      nephrectomy specimen were available for review, the original tumour was on record
      as clear cell RCC. Therefore the two tumours' renal origin was confirmed.

PMID- 9639120
TI  - Clear cell carcinoma of the pancreas: an adenocarcinoma with ductal phenotype.
AB  - AIMS: Primary clear cell carcinoma of the pancreas resembling metastatic renal
      carcinoma has only rarely been described. To date it has been poorly
      characterized as a distinct tumour entity. METHODS AND RESULTS: We report a case
      of clear cell carcinoma in a 53-year-old man involving the head of the pancreas
      and which had a small intraductal papillary component. The clear cell portion
      comprised about 90% of the tumour mass. It showed predominantly a solid growth
      pattern with a few scattered tubular structures. Immunocytochemically the tumour
      cells stained positively for cytokeratins 7, 8, 18 and 19, whereas the reaction
      for vimentin and neuroendocrine markers was negative. K-ras analysis revealed a
      point mutation at codon 12 with mutation of GGT to GAT. CONCLUSION: The
      intraductal tumour component of this clear cell carcinoma as well as the
      cytokeratin pattern and the K-ras mutation suggest that this rare type of
      pancreatic cancer has a ductal phenotype.

PMID- 9639121
TI  - Intrahepatic bile duct loss in primary sclerosing cholangitis: a quantitative
      study.
AB  - AIMS: Intrahepatic bile duct volume density has been evaluated in four cases of
      primary sclerosing cholangitis (PSC) by applying a semiautomatic image analysis
      system to histological sections of surgical biopsies. Comparison was made between
      normal livers and cases of primary biliary cirrhosis. METHODS AND RESULTS: A
      marked decrease in both bile duct volume density in liver (up to 50% of normal
      value) and bile duct volume density in portal tracts (up to 21% of normal value)
      was found. The analysis of correlations between the portal tract size and the
      portal tract volume fraction constituted by bile ducts confirms that the
      destruction mainly affects small and medium-sized ducts. The ratio of bile duct
      to arterial component volume fractions in portal tracts turned out to be inverted
      with respect to that determined in normal liver, showing a decrease of up to 30%
      of normal value. CONCLUSIONS: The features observed in primary sclerosing
      cholangitis, as well as the extent of bile duct loss proved to be quite similar
      to what we had previously described in primary biliary cirrhosis. Thus,
      regardless of the causes and mechanisms leading to the bile duct loss, the
      quantification of ductopenia produced results which are alike for the two
      distinct cholestatic diseases.

PMID- 9639122
TI  - Liver biopsy is a useful predictor of response to interferon therapy in chronic
      hepatitis C.
AB  - AIM: To evaluate the usefulness of easily assessable morphological parameters in
      liver biopsies in order to predict efficacy of interferon-alpha (IFN) treatment
      in patients with chronic hepatitis C. METHODS AND RESULTS: Inflammatory activity
      and fibrosis (according to Scheuer), and the hepatic iron content (according to
      Rowe and DiBisceglie) were assessed in pre-treatment liver biopsies of 73 de novo
      patients with chronic hepatitis C. Furthermore the presence of fat, lymphoid
      aggregates, and bile duct lesions was evaluated. With respect to IFN therapy
      patients were classified as responders alanine aminotransferase (ALT) normal and
      negative hepatitis C virus (HCV) RNA in serum at the end of treatment, n = 33) or
      non-responders (n = 40). Non-responders had more advanced fibrosis (P = 0.0001)
      and more extensive iron storage (P = 0.0008) than responders. In contrast absence
      of stainable iron was frequently (46%) associated with sustained response.
      Absence of fat droplets in hepatocytes was associated with response (P = 0.0001).
      Stepwise logistic regression analysis indicated that the stage of fibrosis, the
      hepatic iron grade, and the presence or absence of fat were independent
      predictors of response. CONCLUSIONS: Liver biopsy provides useful information for
      selection of patients with hepatitis C for IFN therapy.

PMID- 9639123
TI  - A comparative evaluation of immunohistochemical markers for the differential
      diagnosis of malignant pleural tumours.
AB  - AIMS: To determine the value of immunocytochemistry in differentiation of
      malignant pleural mesothelioma from carcinoma in a pleural biopsy using
      commercially available monoclonal antibodies. METHODS AND RESULTS: A panel of
      monoclonal antibodies against keratins, epithelial membrane antigen (EMA),
      epithelial antigen Ber-EP4, carcinoembryonic antigen (CEA), tumour-associated
      glycoprotein (B72.3), Leu-M1, CD30 (Ber-H2), vimentin and desmin, was applied to
      40 cases of malignant pleural mesothelioma and 23 cases of carcinoma metastatic
      to the pleura (16 pulmonary and seven extrapulmonary). Positivities for Ber-EP4,
      CEA, B72.3 and Leu-M1 were found to have the highest nosologic sensitivities
      (87.0%, 65.2%, 52.5% and 43.5%, respectively) and specificities (97.5%, 97.5%,
      100% and 95%, respectively) for carcinoma. Positive staining for vimentin had the
      highest sensitivity (87.5%) with 95.7% specificity for mesothelioma. Positive
      staining for desmin was found in 45% of mesotheliomas and 0% of carcinomas.
      Diagnostic sensitivity and diagnostic specificity (P-values) were calculated for
      these markers. In respect to the diagnostic power defined by the clinically
      relevant predictive values of positive and negative tests, we found that a two
      marker panel of antibodies including vimentin and Ber-EP4 is most useful for the
      histopathological distinction between carcinoma (pulmonary or extrapulmonary) and
      malignant pleural mesothelioma. CONCLUSIONS: A combination of Ber-EP4 and
      vimentin provides the most sensitive and specific pair of markers for
      distinguishing between malignant pleural mesothelioma and carcinoma metastatic to
      the pleura. The prevalence of the tested tumours should be taken into account
      when evaluating the clinical value of ancillary techniques in pathology.

PMID- 9639124
TI  - Epithelioid haemangioendothelioma of the thyroid gland: a case report and review
      of literature.
AB  - AIMS: This is a hitherto unreported case of an epithelioid haemangioendothelioma
      of the thyroid gland. METHODS AND RESULTS: The patient was a 44-year-old woman
      who presented with a right thyroid mass. A right subtotal thyroidectomy was
      performed. Histologically the lesion had characteristic epithelioid and spindle
      cell proliferation in a background of chondromyxoid stroma. Cytoplasmic
      vacuolization in the epithelioid and spindle cells was present. No atypical
      mitotic activity or necrosis was noted. The tumour cells were positive for factor
      VIII-related antigen, Ulex europeus and CD 31 and were negative for cytokeratin.
      CONCLUSION: The patient has been followed for 24 months and is free of recurrent
      and metastatic disease, which is supportive of a benign course in the thyroid
      gland.

PMID- 9639125
TI  - Primary primitive neuroectodermal tumour of the urinary bladder.

PMID- 9639126
TI  - Prostate-specific antigen and the salivary gland.

PMID- 9639127
TI  - Squamoid eccrine ductal carcinoma.

PMID- 9639128
TI  - Proteinaceous deposits and lipidic histiocytosis in follicular lymphoma.

PMID- 9639129
TI  - An unusual granulomatous form of chronic pyelonephritis mimicking tuberculosis.

PMID- 9639130
TI  - Large cell carcinoma of lung with osteoclast-like giant cells.

PMID- 9639131
TI  - The double muscularis mucosa in ulcerative colitis: is it all new?

PMID- 9639132
TI  - Outcomes research and cost-effectiveness analysis in radiology.

PMID- 9639133
TI  - Receiver operating characteristic (ROC) analysis: basic principles and
      applications in radiology.
AB  - Receiver operating characteristic (ROC) analysis is a widely accepted method for
      analyzing and comparing the diagnostic accuracy of radiological tests. In this
      paper we will explain the basic principles underlying ROC analysis and provide
      practical information on the use and interpretation of ROC curves. The major
      applications of ROC analysis will be discussed and their limitations will be
      addressed.

PMID- 9639134
TI  - The cost-effectiveness of the diagnosis of renal artery stenosis.
AB  - The objective of this study was to assess the cost effectiveness of eight
      strategies to diagnose renovascular hypertension (RVHT) followed by treatment
      with percutaneous transluminal angioplasty (PTRA) with or without stent
      placement. The eight diagnostic strategies were compared with a reference
      strategy, i.e. antihypertensive medication. The diagnostic imaging techniques
      under consideration were captopril renography, spiral computed tomography
      angiography (CTA), magnetic resonance angiography (MRA) and conventional
      angiography. Cost-effectiveness analysis was carried out from the perspective of
      the health care system, based on data from the literature. A model was developed
      to predict the reduction in 10-year morbidity and 10-year mortality owing to
      myocardial infarction, stroke and chronic renal failure achieved after PTRA
      compared with the reference strategy. Life-years gained over a 10-year follow-up
      period and the incremental cost-effectiveness ratio per life-year saved were the
      outcome measures. The strategy CTA followed by angiography was more effective,
      but more costly, than captopril renography followed by angiography, with an
      incremental cost-effectiveness ratio per life-year gained of Dfl 64700. Combining
      captopril renography with CTA was even more effective, but the incremental cost
      effectiveness ratio per life-year gained was Dfl 236400. Strategies including MRA
      were not cost-effective. The results suggest that diagnostic strategies that
      include CTA are more effective than captopril renography in detecting renal
      artery stenosis (> 50%) and cost saving due to prevented myocardial infarction,
      stroke or chronic renal failure. MRA is even more effective, but in order to
      achieve an acceptable cost-effectiveness ratio, the costs would need to be
      reduced. The cost-effectiveness of the diagnostic strategies is sensitive to the
      pre-test probability of RVHT. So, careful clinical evaluation, in order to
      achieve a pre-test probability of at least 20%, is an essential component of the
      complete workup strategy in patients suspected to have RVHT.

PMID- 9639135
TI  - Clinical trials: study design and analysis.
AB  - To enable doctors to select the best therapeutic strategy, the value of the
      various options needs to be determined. The best approach to the evaluation of
      therapeutic effectiveness and side effects is a randomised clinical trial.
      Traditionally, such trials have been mainly conducted to evaluate new drugs.
      However, other medical interventions, such as surgical and radiological
      procedures and lifestyle changes, also require methodologically sound evaluation.
      In this article, some of the basic principles of the study design of randomised
      clinical trials will be discussed, such as study group comparability, treatment,
      data collection and statistical analysis, as well as issues relating to
      randomisation, outcome and blinding. Attention is also paid to some of the
      ethical aspects.

PMID- 9639136
TI  - Advances in radiology and the real versus apparent effects of early diagnosis.
AB  - Over the last two decades, technological advances in radiology have
      revolutionized the practice of medicine. Although the potential benefits of these
      advances are well recognized, the potential harms are not. This paper describes
      how early diagnosis can cause overestimations of disease prevalence and the
      effectiveness of intervention. The paper begins by demonstrating how the observed
      prevalence of disease increases with the sensitivity of the test and by
      explaining the concept of pseudodisease. Next, the paper explains how lead time
      bias, length bias and overdiagnosis bias cause overestimations of the
      effectiveness of earlier diagnosis and associated treatments. These biases
      pertain to both the detection and staging of disease. In addition, the paper
      explains how these overestimations of disease prevalence and the effectiveness of
      intervention can initiate a cycle of increasing testing and treatment, which may
      eventually cause more harm than benefit. Finally, randomized clinical trials and
      decision analysis are discussed in the context of evaluating new testing
      strategies.

PMID- 9639137
TI  - Economic analyses of radiological procedures: a methodological evaluation of the
      medical literature.
AB  - OBJECTIVE: Increasing pressure to curb health care costs has led to considerable
      interest in economic analyses, including both cost-effectiveness and cost-benefit
      analyses. Numerous economic analyses of radiological procedures have appeared in
      both the radiology and non-radiology literature. The objective of this study was
      to evaluate the methodological quality of economic analyses of radiological
      procedures published in the non-radiology medical literature during the years
      1990 1995. METHODS: Original investigations from the medical (non-radiological)
      literature that include economic analyses of radiological interventions were
      identified from a computerized literature search. Each economic analysis article
      was evaluated by two independent reviewers for adherence to ten methodological
      criteria. The criteria were derived from review of the medical and radiological
      economic analysis methodology literature and consisted of the following: (1)
      Comparative options stated; (2) perspective of analysis defined; (3) outcome
      measure identified; (4) cost data included; (5) source of cost data stated; (6)
      long term costs included; (7) discounting employed; (8) summary measure provided;
      (9) incremental computation method used; and (10) sensitivity analysis performed.
      The results were compared to a previous study that evaluated the radiological
      literature. RESULTS: Of the 56 articles in the medical literature that included
      economic analyses of radiological procedures, only eight (14%) conformed to all
      ten methodological criteria. The cost data (98%) and comparative options (89%)
      criteria exhibited high compliance, while the perspective of analysis (25%) and
      discounting (32%) criteria had relatively low compliance. Agreement between the
      reviewers was excellent (kappa = 0.88). CONCLUSIONS: Published economic analyses
      of radiology procedures usually do not meet accepted methodological standards.

PMID- 9639138
TI  - Meta analysis of the relationship between tuberous sclerosis complex and renal
      cell carcinoma.
AB  - The association of angiomyolipoma with tuberous sclerosis complex (TSC) patients
      is well recognised. Some literature has suggested that patients with TSC are at
      increased risk of renal neoplasm, particularly since angiomyolipomas can be
      locally invasive and demonstrate tumor like neovascularity on angiography. In an
      attempt to place in context one case of metastatic renal cell carcinoma in a
      patient with TSC a meta analysis of the literature was performed. One pediatric
      patient with TSC and metastatic renal cell carcinoma was evaluated. Reviews and
      case reports of TSC and renal cell carcinoma and related imaging findings were
      identified by searching the MEDLINE database, the 'bibliography of reviews' in
      Index Medicus, personal files and the reference lists from all identified
      reviews. Individual cases suitable for review in the available literature from
      1922 through 1993 comprised the data base. The data base was analysed with the
      method of proportions and unpaired two-tailed Student's t-test for different
      populations. A cumulative summary of the literature amassed 107 additional cases
      from 62 reports over 71 years. Our case is the 17th case, to our knowledge, of
      renal cell carcinoma in TSC. Analysis of the distribution of characteristics and
      incidence of; renal cysts, renal cell carcinoma, and lymph node involvement
      demonstrate no increased risk of renal cell carcinoma in patients with TSC (P =
      NS). Though anecdotal evidence has suggested a relationship between TSC and renal
      cell carcinoma, meta analysis of cases of coincident TSC renal complex, cystic
      changes, angiomyolipoma and renal cell carcinoma implies an identical, though
      small, risk of malignancy in TSC patients as compared with the normal population.

PMID- 9639139
TI  - Minor cerebral alterations observed by magnetic resonance imaging in syndromic
      children with mental retardation.
AB  - OBJECTIVE: To evaluate the anomalies of the central nervous system (CNS) by
      magnetic resonance imaging (MRI) in normal subjects and in syndromic patients.
      METHODS AND MATERIAL: Seventy-three normal subjects and 50 different syndromic
      patients with mental retardation (from 3 months to 16 years) were studied
      utilizing several morphometric parameters (degree of myelination of the white
      matter, evaluation of liquoral spaces, septo-caudate distance, Evans index,
      Aboulezz method, and length, width and angles of corpus callosum). RESULTS: A
      high frequency of anomalies of the corpus callosum, the Chiari anomaly and
      alterations either of the white matter or of the ventricular and periencephalic
      system have been observed. CONCLUSION: The authors point out the importance of
      cerebral MRI in the study of CNS in patients with malformation syndromes. The
      present research, carried out on a large number of both normal subjects and
      patients with malformation syndromes, represents one of the first systematic
      studies in this field.

PMID- 9639140
TI  - Cutis verticis gyrata: its computed tomographic demonstration in acromegaly.
AB  - A retrospective review of the 17 cases of acromegaly, recorded in the hospital
      and with available CT scans was undertaken in order to determine the presence and
      of cutis verticis gyrata (CVG) frequency, and the spectrum of other associated
      radiographic appearances of CVG. The hormone levels were analysed, and the
      histopathology of the surgical specimens reviewed. Five cases were uncovered. In
      these, the scalp in CVG was markedly thickened with convoluted, gyriform or cog
      wheel appearances. There was no correlation in the age, sex, duration of symptoms
      or the hormone levels in these two groups of acromegalics: with or without CVG.
      All cases were histologically pituitary adenoma. It is concluded that CVG is not
      uncommon in acromegaly. Its presence on a CT scan should caution the radiologist
      to the presence of pituitary adenoma or any of the other neurological causes of
      CVG.

PMID- 9639141
TI  - Oesophageal narrowing in chronic granulomatous disease.
AB  - A 14 year-old boy with X-linked chronic granulomatous disease (CGD) developed a
      long smooth narrowing at the mid oesophagus with severe dysphagia. Endoscopy
      revealed a normal mucosa and biopsy showed non-specific acute inflammatory
      changes. Bacterial cultures of the biopsy specimens were sterile. Combined
      treatment with antibiotics and steroids resulted in a transitory remission, but
      symptoms recurred after 2.5 months. One second course of steroids and antibiotics
      lead to a long-term remission. Oesophagogram was more useful than endoscopy to
      evaluate the severity of the stricture.

PMID- 9639142
TI  - MR imaging of meniscal tears with discoid lateral meniscus.
AB  - OBJECTIVE: To study MR findings of meniscal tears with discoid lateral menisci
      (DLMs) and to evaluate the incidence and accuracy of MRI compared to
      arthroscopical surgery. MATERIAL AND METHODS: MR appearances of surgically proved
      torn discoid lateral menisci (DLM) were studied in 57 knees (40 patients). They
      were all performed with a 1.5T MR before surgery. MR sequences included T1- and
      T2* weighted images on both coronal and sagittal planes and 3D-axial images with
      a slice thickness of 0.7 mm. RESULT: Of 57 DLMs, there were 32 complete DLMs and
      25 incomplete DLMs. Twenty-five of 32 complete DLMs had tears; including seven
      with intrasubstance tear, five with radial tear, five with other kinds of tears
      and eight with severe tears involving whole meniscus. On the other hand, 13 of 25
      incomplete DLMs had tears; including two with intrasubstance tear, six with
      radial tear, four with other kinds of tears and one with severe tears. All DLMs
      were correctly diagnosed on MR images. Twenty-seven of 38 tears with DLM were
      correctly identified on conventional 2D MR images. This yielded 71.1%
      sensitivity, 100% specificity and 80.7% overall accuracy. When adding axial 3D MR
      images to 2D MR images, 36 of 38 tears were correctly diagnosed. A combination of
      both techniques yielded a sensitivity of 94.7% and a specificity of 100%. Ten of
      11 radial tears with DLM were correctly identified on 3D axial images, where only
      three of them could be diagnosed on conventional 2D images. Eight of nine
      intrasubstance tears were correctly identified on 3D axial images, where six of
      them could be diagnosed on conventional 2D images. CONCLUSION: DLMs had a much
      higher incidence of meniscal tears than normally shaped lateral menisci and MR is
      the only modality of choice to evaluate them before surgery. Especially 3D axial
      MR images were quite useful in the detection of intrasubstance and radial tears
      often associated with DLMs.

PMID- 9639143
TI  - Intramuscular low flow vascular malformations: treatment by means of direct
      percutaneous embolization.
AB  - PURPOSE: Intramuscular hemodynamically inactive vascular malformations are
      infrequent entities whose surgical treatment is often impossible, crippling, or
      inefficient. We describe a nonsurgical therapeutic approach consisting on
      embolization by direct puncture with sclerosant substances. METHODS: Four
      patients have been treated from April to November 1994, three female and one
      male, ranging in age from 13 to 31 years. Three vascular malformations were
      located in the quadriceps and one in the deltoid muscle. The point of access was
      determined with information provided by MR. The skin was cleaned with an
      antiseptic solution and puncture was performed with a 22 gauge Chiva needle.
      Blood flow inside the malformation was slow in all cases and no afference to the
      normal venous system was detected. We embolized with 5-15 cc (mean 7.5 cc) of a
      mixture of ethibloc and ethanol. RESULTS: The mean follow-up period was 17 months
      (range 14-21). All patients remain asymptomatic and have resumed normal daily
      life activities. There were no complications. CONCLUSION: Percutaneous
      embolization by direct puncture of intramuscular vascular malformations is a
      feasible and simple procedure. Our preliminary results are promising, although
      more extensive studies need to be to performed in order to reach definite
      conclusions.

PMID- 9639144
TI  - A validation of a flow quantification by MR phase mapping software.
AB  - AIM: We evaluated a Siemens software of flow quantification (FQ) by MR phase
      mapping, in the framework of a common practical use. METHODS: Experiments with a
      laminar flow phantom and in vivo pulsatile flow were performed. In particular, FQ
      in ascending aorta was investigated in healthy volunteers. RESULTS AND
      CONCLUSION: Flow phantom experiments reveal that the FQ slightly underestimates
      (8% on the average) actual velocities (mean velocities over a vessel area), and
      also that velocity uncertainties are related to the encoding velocity value,
      whatever the measured velocity. Furthermore, using well characterized working
      criteria, we found low intraobserver variability and negligible interobserver
      variability in ascending aorta FQs. The role played by the choice of reference
      area in FQ accuracy is emphasized. When recording several cardiac cycles during
      the same acquisition, it is shown that the FQ software may provide erroneous
      results. Several comments for FQ software use in the ascending aorta are added.

PMID- 9639145
TI  - Gossypol as a male antifertility agent--why studies should have been continued.
AB  - It has been nearly three decades since the beginning of nationwide research into
      gossypol as a male antifertility agent in China. Several lines of data
      implicating some side effects of gossypol were published which led to the
      termination of this area of research in China. The present review re-examines
      these data and points out the confusion surrounding issues such as hypokalaemia,
      irreversible azoospermia and other side effects. The prospects and related
      difficulties for gossypol as a potential male contraceptive are also discussed.

PMID- 9639146
TI  - Gossypol: reasons for its failure to be accepted as a safe, reversible male
      antifertility drug.
AB  - Following clinical trials conducted in China in the 1970s, gossypol was proposed
      as a drug for male contraceptive use. This review summarizes the extensive
      investigations on formal animal toxicology and on the recovery of fertility in
      men after stopping gossypol treatment which led to the decision by the Special
      Programme of Research, Development and Research Training in Human Reproduction
      (HRP) at the World Health Organization (WHO), that gossypol would not be
      acceptable as an antifertility drug. It is concluded that the assessment of
      gossypol reinforces the mandatory requirement that future contraceptive drugs
      must be developed by the established routes of appropriate animal toxicology and
      phased clinical studies.

PMID- 9639147
TI  - Centromere sequences localize to the nuclear halo of human spermatozoa.
AB  - Chromatin is organized into a series of discrete nuclear matrix-associated and
      non-nuclear matrix-associated domains. The non-matrix-associated domains consist
      of loops of DNA that are attached to the proteinaceous nuclear matrix by matrix
      associated regions (MARs). Although this organization is well characterized in
      somatic cells, comparatively little is known of this mode of organizing the
      genome in the human sperm nucleus. To define this relationship, the interaction
      of human sperm chromatin with the nuclear matrix was assessed by fluorescence in
      situ hybridization using specific alpha satellite probes directed to the
      centromeric regions of chromosomes 13 plus 21 and 18. Hybridization of the
      centromeric sequences was visualized as segmented, bundled structures that
      extended from the nuclear core into the halo.

PMID- 9639148
TI  - Binding of seminal vesicle proteins to the plasma membrane of rat spermatozoa in
      vivo and in vitro.
AB  - The association of seminal vesicle (SV) proteins with rat spermatozoa has been
      studied in vivo and in vitro. SV proteins bind to the sperm plasma membrane after
      ejaculation but are removed progressively from the sperm plasma membrane in the
      female genital tract. Although some of these remain bound to spermatozoa when
      they reach the oviducts, they do not seem to be present at the time of
      fertilization. This could indicate a putative role for these SV proteins in pre
      fertilization events. In addition, the binding of SV antigens was studied in
      vitro. It was observed that the ability to bind SV proteins is gained by the
      spermatozoa during epididymal maturation, and is first detectable in spermatozoa
      collected from the cauda epididymis. On the other hand, the binding is regulated
      by other proteins present in the ejaculate which are secreted by the coagulating
      glands. Experiments also showed that mouse spermatozoa are able to bind rat SV
      proteins, indicating that the binding is not a highly species-specific
      phenomenon.

PMID- 9639149
TI  - Effects of nitrogenous components of urine on sperm motility: an in vitro study.
AB  - The effects of the major nitrogenous components of urine (ammonia, creatinine,
      urea and uric acid) on sperm motility were investigated. Semen samples were
      obtained by masturbation from a young volunteer with a normal spermiogram and
      fertility. Sperm motility was measured using a Sperm Quality Analyzer and Makler
      Chamber. When semen was mixed with a urine sample for which acidity and
      osmolality were adjusted to pH 7.5 and 340 mOsm/kg, the higher the concentration
      of the urine, the poorer the sperm motility. When solutions of various
      concentrations of the nitrogenous compounds which are excreted in urine were
      mixed with semen, sperm motility decreased in proportion to ammonia levels and
      was markedly decreased after 30 min. However, in the case of creatinine, urea and
      uric acid, good motility was maintained for 30 min regardless of their amounts.
      In conclusion, urine ammonia content is detrimental to sperm motility and may be
      an important factor in retrograde ejaculation.

PMID- 9639151
TI  - Performance of the sperm quality analyser in predicting the outcome of assisted
      reproduction.
AB  - The present study was undertaken to assess the relationship between the results
      of conventional semen analysis and the sperm motility index (SMI) as measured by
      the sperm quality analyser (SQA), and to evaluate these in relation to the
      fertilization and/or pregnancy outcome of assisted reproduction. SMI
      determinations and conventional semen analyses were performed on 223 samples from
      subfertile men in two laboratories in Leuven (n = 136) and Antwerp (n = 87), and
      on spermatozoa prepared on a Percoll gradient (n = 136) used for treatment of
      male factor infertility in 57 cycles of intrauterine insemination (IUI), 44
      attempts at in vitro fertilization (IVF) and 31 attempts at intracytoplasmic
      sperm injection (ICSI). SMI values for native semen correlated significantly with
      sperm concentration, motility and morphology. Multiple regression analysis
      revealed sperm concentration after preparation, and the concentration of motile
      spermatozoa with normal morphology and SMI (before preparation) to be the
      independent determinants for SMI after preparation. SMI values were significantly
      higher after, than before, preparation (p < 0.0001). In regular IVF (n = 44) the
      percentage of fertilized oocytes correlated significantly (p < 0.05) with sperm
      motility (A + B%, r = 0.33), with the percentage of spermatozoa with normal
      morphology (r = 0.46) before preparation, with the values of SMI both before and
      after preparation (r = 0.54, r = 0.48), with sperm concentration (r = 0.34) and
      with the motile sperm concentration (r = 0.29) after preparation. For the
      occurrence of pregnancy (all treatment methods), comparison of areas under ROC
      curves (AURC) indicated motile sperm concentration after preparation, as well as
      SMI both before and after preparation, to have the highest AURC, with no
      significant difference between these values as far as predictive power was
      concerned. These results indicate that the SQA allows for rapid evaluation of
      sperm characteristics and of the effectiveness of sperm preparation techniques.
      However, it is not superior to conventional semen analysis in predicting the
      outcome of assisted reproduction.

PMID- 9639150
TI  - Characterization and expression of a stage specific antigen by monoclonal
      antibody TRA 54 in testicular germ cells.
AB  - To study the mechanism of spermatogenesis, we have isolated many monoclonal
      antibodies (mAb) which recognize specific steps of mouse germ cell
      differentiation and then have evaluated the specific expression and
      characterization of antigenic molecules using immunohistochemistry and Western
      blotting. Monoclonal antibody TRA 54 recognized specific organelles in germ cell
      cytoplasm from spermatocytes to spermatids; that is, a large granule was stained
      in mid-late pachytene, diplotene and secondary spermatocytes and in round
      spermatids at stage I while the acrosome of spermatids at steps 2-3 to step 12
      were also positive. Thereafter, the antigens disappeared from spermatids at more
      advanced stages of differentiation. Western blots using TRA 54 revealed broad
      bands with approximate molecular weights of >200, 190 and 85 kDa in the testis.
      The expression of these antigens during testicular germ cell development should
      be of interest in relation to the biogenesis of organelles such as the chromatoid
      body and acrosome and will be a useful stage-specific molecular marker for the
      study of spermatogenesis.

PMID- 9639152
TI  - Semen levels of mitochondrial DNA deletions in men attending an infertility
      clinic do not correlate with phenotype.
AB  - In view of previous reports associating mitochondrial DNA deletions with male
      reproductive disorders, levels of the 'common' 4977 bp mitochondrial DNA deletion
      were evaluated semi-quantitatively in 64 men, without prior knowledge of the
      clinical diagnosis. Significant levels of deletions were detected in 34/64 men
      (53%) but 29 of these (45%) had a normal semen profile and were phenotypically
      normal. No deletions were detected in 30 men, of whom 21 were normospermic, six
      were oligozoospermic and three were azoospermic. It is concluded that although
      mitochondrial DNA deletions within the testis may be associated with primary
      testicular disease, no correlation with semen quality was evident in this study,
      thus limiting its potential use as a diagnostic test.

PMID- 9639153
TI  - Asymmetrical testicular weights in mammals, birds, reptiles and amphibia.
AB  - The testes of different classes of animals (mammals, birds, reptiles and
      amphibia) were weighed. Some species showed inconsistent left-right asymmetric
      testicular weights, while other species (including amphibians, reptiles, some
      birds and some mammals) showed consistent asymmetry in their weights. In rodents,
      for example, five strains of mice consistently exhibited asymmetrical testes,
      with the right testis always being heavier than the left. In contrast, another
      strain of mice showed inconsistent bilateral asymmetry of the testes.

PMID- 9639154
TI  - Validation of a recording protocol for assessing temporomandibular sounds and a
      method for assessing jaw position.
AB  - Sounds are often produced by the temporomandibular joint (TMJ) during movement in
      both symptomatic and asymptomatic subjects. However, subjective methods of
      describing these sounds have been shown to have poor inter- and intra-observer
      reliability. In this study, a low cost system in which TMJ sounds were detected
      using the loudspeakers of lightweight in-ear headphones as microphones is
      evaluated. The sounds were recorded on tape and then analysed using a computer.
      Sounds were elicited by asking subjects to bring their teeth together with
      sufficient force to produce a tooth contact sound, then open their mouths as far
      as possible and then close again. Placing the microphones in the ears attenuated
      ambient sounds by 58%, thus providing a degree of immunity from ambient noise.
      Sampling was performed on the left microphone only at 3.4 kHz and from the left
      and right microphones together at 1.7 kHz for 60 TMJ sounds and 60 tooth contact
      sounds. Spectral analysis of sounds recorded at the two sample rates revealed no
      significant differences. Therefore, a sample rate of 1.7 kHz is adequate to
      resolve the frequency components present in the TMJ sounds. Although simply
      recording TMJ sounds does not give a direct measurement of the position of the
      mandible, using this protocol allows the length of the open close cycle to be
      determined. If the envelope of movement is assumed to approximate a sinusoid,
      then the direction of mandibular movement can be assumed to reverse at the half
      way point in the cycle. The accuracy of this assumption was calculated by
      comparing the mid-point of the cycle to the point of maximum gape in 129 cycles
      from nine subjects. The mean difference expressed as percentage of cycle length
      was 1.3 +/- 0.9%.

PMID- 9639155
TI  - Two-dimensional configuration of the myoneural junctions of human masticatory
      muscle detected with matrix electrode.
AB  - Motor unit action potentials (MUAPs) propagate bidirectionally from the myoneural
      junction along the muscle fibre. The propagation of excitation within single
      motor units can be detected during sustained isometric contraction using a
      surface electrode array. Electromyographic (EMG) signals from an adjacent pair of
      contacts along the muscle fibres show a very similar wave form with a time shift.
      In the present study, EMG signals of the masseter and the temporal muscles were
      obtained from two male adults during clenching in the intercuspal position using
      the multichannel surface electrode with 17 x 11 contacts. The two-dimensional
      location of the myoneural junction for each column from the source of the
      propagation was estimated. Each of the myoneural junctions was located in the
      lower portion of the masseter muscle and in the upper portion of the temporal
      muscle. However, the junction was distributed within 10 mm along the muscle
      fibres at different contraction levels in each muscle. This noninvasive technique
      of multiple surface electrodes enabled us to add to knowledge of the anatomical
      structure of the masticatory muscles examined.

PMID- 9639156
TI  - A comparison between the wear resistance of three types of denture resin to three
      different dentifrices.
AB  - This study compares the abrasive effects of three dentifrices on three different
      denture base resins, a heat cured acrylic resin, a self cured acrylic resin and a
      light activated urethane dimethacrylate-based resin. Specimens of the resins were
      subjected to a regimen of mechanical brushing using measured amounts of paste on
      standard toothbrushes driven by a reciprocating device. The apparent wear of each
      specimen was assessed qualitatively using scanning electron microscopy and
      quantitatively using profilometry and reflex microscopy. The study showed that
      cleaning pastes play a significant role in the wear of conventional acrylic
      resins, the relative abrasivity of the dentifrices being substrate related.
      However, wear was less evident on the light activated urethane dimethacrylate
      resin. Brushing with water alone produced no detectable wear on any of the
      specimens.

PMID- 9639157
TI  - Cerana--a new method for the restoration of teeth with prefabricated ceramic
      inlays.
AB  - Cerana are all-ceramic, prefabricated inlays which replace enamel and are
      produced in a lucite-reinforced glass ceramic. To evaluate the clinical quality
      of Cerana inlay therapy, 38 patients with a total of 60 inlays were examined in a
      retrospective cross-sectional study. The inlays were primarily of Class I type,
      but even Class II tunnel preparations and Class V were examined. The median age
      of the inlays was 1.5 years. A modified form of the California Dental Association
      criteria was used in the evaluation. The results show that all inlays were of
      excellent or acceptable character in terms of marginal fit, colour and surface
      roughness. None of the patients reported any post-operative symptoms of pain. One
      restoration had secondary caries and a fractured marginal ridge. One restoration
      with poor anatomical form caused by a fractured filling and one restoration with
      deep marginal discolouration were discovered. Although the follow-up time was
      short, the results show that Cerana can be considered an interesting alternative
      to other tooth-coloured materials on the market.

PMID- 9639158
TI  - Curing depth of four composite veneering materials polymerized with different
      laboratory photo-curing units.
AB  - Post-curing properties of composite materials are influenced by the type of base
      monomer, activation system, filler content, and also by the type of light source
      employed. This study examined curing depth of four composite veneering materials
      polymerized by means of two different high-intensity photo-curing units for the
      purpose of evaluating the curing performance of the combinations of composite
      material and photo-curing unit. Two microfilled and two hybrid composite
      materials designed for prosthetic veneer were assessed. The composite materials
      were cured using two photo-curing units, one with a xenon light source and one
      with two metal halide light sources, and exposure periods varied from 20 to 90 s.
      Curing depth of the materials was determined with a scraping technique described
      by the International Organization for Standardization (ISO 4049). Three-factor
      analysis of variance revealed that the depth of cure was influenced by the type
      of composite material as well as by the photo-curing unit, and also by the
      exposure period (P = 0.0001). A microfilled composite material (Dentacolor)
      demonstrated the greatest depth of cure (4.69 mm) after 90 s irradiation with a
      metal halide unit (Hyper LII). Of the two photo-curing units, the metal halide
      curing unit consistently exhibited greater depth of cure than the xenon curing
      unit (Dentacolor XS). Longer exposure increased the depth of cure for all
      combinations.

PMID- 9639159
TI  - Ratio between vertical and horizontal mandibular range of motion.
AB  - Mandibular range of motion (ROM), vertical and horizontal, is often measured as a
      part of a diagnostic assessment of temporomandibular joint disorders. In the
      literature, a fixed ratio between the vertical and the horizontal ROM has been
      suggested, i.e. 4:1. The ratio is frequently used to predict the vertical ROM on
      the basis of the horizontal ROM and vice versa. However, no scientific data are
      available to substantiate the ratio suggested. The aim of this study was to
      determine whether the fixed ratio of 4:1 exists and, if so, whether this ratio
      has a predictive value. Vertical and horizontal mandibular ROM was measured in 91
      healthy subjects, 59 women, and 32 men (mean age 27.2 years, s.d. 7.4 years)
      using vernier callipers. We found a mean ratio between vertical and horizontal
      ROM ranging from 6.0:1-6.6:1. On an individual basis the ratio ranged from 3.6
      15.5. Correlations between vertical and horizontal ROM were weak. On the basis of
      the results on this study it is concluded that the ratio between vertical and
      horizontal ROM is approximately 6:1 rather than 4:1, and that the ratio has poor
      predictive value.

PMID- 9639160
TI  - Properties of four composite veneering materials polymerized with different
      laboratory photo-curing units.
AB  - This study examined properties of four composite veneering materials polymerized
      with two different photo-curing units for the purpose of evaluating curing
      performance of the combination of composite material and curing unit. Two
      microfilled (Dentacolor and Thermoresin LC II) and two hybrid (Cesead II and
      Solidex) composite materials designed for prosthetic veneer were selected. The
      respective light sources of the units were a xenon (Dentacolor XS) and a metal
      halide (Hyper L II) lamp. The composite materials were exposed with the photo
      curing unit for 60 s on each side (i.e. from top and bottom). Knoop hardness,
      compressive strength, flexural strength, flexural modulus, water absorption and
      water solubility were determined according to standardized testing methods. The
      specimens exposed with the metal halide unit generally exhibited greater Knoop
      hardness number, and compressive strength and lower solubility than those exposed
      with the xenon unit. A microfilled material (Thermoresin LC II) cured with the
      metal halide unit exhibited significantly improved results for all tests as
      compared with the same material cured with the xenon unit.

PMID- 9639161
TI  - Detection of onset and termination of muscle activity in surface electromyograms.
AB  - A method of automated detection of onset and termination of rhythmic muscle
      activity in electromyograms (EMGs) is presented. A threshold level in the EMG is
      computed, such that amplitudes in the EMG signal exceeding this level indicate
      muscle activity. The threshold level is determined using a statistical criterion
      based on the amplitude distribution of the entire EMG signal. The working of the
      method is illustrated with EMG signals recorded from chewing muscles. EMG signals
      with a good as well as a worse signal-to-noise ratio are presented. The method
      can be used for any EMG signal containing cyclic bursts of activity and thus may
      be applied in studies on rhythmic movements, such as chewing, walking and
      breathing. An automated method of EMG burst detection has the advantage that
      large amounts of EMG data can be easily and objectively processed.

PMID- 9639162
TI  - Comparison of the most comfortable mandibular position with the intercuspal
      position using cephalometric analysis.
AB  - For evaluation of the most comfortable position (MCP) in edentulous subjects, as
      decided by mandibular position sense, the MCP was recorded in ten edentulous
      subjects and compared with the intercuspal position (ICP) of normal dentate
      persons. It was found that the MCP was at a lower mandibular position than the
      ICP; the facial height was markedly reduced in the former by a front-upward
      rotation of the mandible centering around the condyles. Thus, it has been
      suggested that the occlusal vertical dimension (OVD) of the MCP in the restored
      dentition is less than that of the original ICP.

PMID- 9639163
TI  - Posterior bite collapse--revisited.
AB  - Although there are different definitions of posterior bite collapse, only the
      classical definition of Amsterdam provides a definite diagnosis and treatment
      plan. This situation entails a subtle loss of the occlusal vertical dimension
      with resultant flaring of the maxillary incisors. Other causes for flaring, such
      as derangements of form and functions of lips and tongue, bruxism, habits, as
      well as the presence of advanced periodontal disease or malocclusions, should be
      ruled out before the diagnosis of posterior bite collapse can be made. The
      complexity of differential diagnosis is illustrated with three case reports.

PMID- 9639164
TI  - Examination of the diagnostic value and estimation of the chaos phenomenon in
      masticatory movement using fractal dimension in patients with temporomandibular
      dysfunction syndrome.
AB  - The aim of this study was to estimate the chaos phenomenon (chaos) in masticatory
      movements using the fractal dimension (FD), and to examine the diagnostic value
      of the fractal dimension in comparing stomatognathic functional disturbances with
      normal stomatognathic function. The subjects were all high school students and
      included nine subjects presenting with acceptable normal occlusion, 18 subjects
      with TMJ dysfunction syndrome and seven subjects with tooth crowding. Masticatory
      movements were obtained during free, right side, and left side gum-chewing and
      were used to calculate the capacity dimension in the FD. Chaos in the masticatory
      movement was estimated by the FD saturated with some constant value to an
      increase of embedding dimension (approached a plateau). In the crowding group,
      the FD was also significantly high on the sagittal plane in comparison with the
      normal. In the patients with pain, the FD on the sagittal plane was significantly
      high. In the patients with pain and closed lock, the FD on the frontal plane was
      significantly high. However, in the patients with pain and with reduction of
      anterior disc displacement, the FD was significantly low on the horizontal plane.
      These findings suggest that chaos is present in masticatory movements and the
      difference in the FD are of diagnostic value in evaluation of the relationship
      between FD and stomatognathic functional disturbance.

PMID- 9639165
TI  - Monitoring the state of the occlusion--gnathosonics can be reliable.
AB  - Monitoring the state of the occlusion should include records that can be
      compared. Gnathosonics has not become generally accepted as an everyday method of
      assessing the quality of the occlusion. It is suggested that this may be due to
      inconsistencies in the results obtained by various workers in the field. It is
      further suggested that such inconsistencies could be due to the manner of data
      gathering in the areas of equipment, transfer of data from the patient and
      interpretation of the records. A reliable method of data gathering using
      accelerometers is suggested and, taking account of the complexities of sound
      transmission through the skull, concludes that the overall envelope of the sounds
      produced by the occlusion of the teeth is more informative that the actual
      frequencies generated. Ways in which gnathosonics could be placed on a scientific
      footing and areas where further investigation might be useful are suggested.
      Gnathosonics, properly controlled, can provide a simple, quick and reliable
      method of making permanent records of occlusal sounds for comparison and
      assessment of stability or change in the state of the occlusion.

PMID- 9639166
TI  - The making and the breaking of senescence: changes of gene expression during
      cellular aging and immortalization.

PMID- 9639167
TI  - Metabolite concentrations in skeletal muscle of different aged rats submitted to
      hypoxia and pharmacological treatment with nicergoline.
AB  - The energy metabolism of the gastrocnemius and soleus muscles in young-adult,
      mature, and senescent rats was evaluated after 72 h of continuous exposure to
      normobaric hypoxia or normoxia. The effects of treatment with the alpha
      adrenergic antagonist nicergoline were also investigated. In the gastrocnemius
      muscle we evaluated the concentrations of some significative metabolites involved
      in anaerobic glycolysis and the Krebs' cycle, free amino acids related to the
      Krebs' cycle, ammonia, some energy mediators, and the energy store creatine
      phosphate. In the soleus muscle a selection of these was evaluated. In both
      muscles aging was similarly characterized by a decrease in muscular creatine
      phosphate concentration, while the energy mediators and the energy charge
      potential remained unchanged. Singly, some gastrocnemius muscle metabolites
      showed linear changes in their concentrations with aging, while for the soleus
      muscle the only linear change regarded glucose-6-phosphate. Continuous normobaric
      hypoxia induced greater changes at the age of 4 and 24 months than at 12 months.
      Chronic treatment with nicergoline modified the influence of hypoxic conditions
      on muscle metabolites concentrations only in some cases, regardless of the age of
      the animals. Further investigations are necessary before any firm conclusions can
      be drawn about the pharmacological activity of nicergoline on hypoxia in aged
      rats.

PMID- 9639168
TI  - Effect of chronic hyperoxia on young and old rat carotid body ultrastructure.
AB  - Morphologic, physiological, and biochemical changes occur in the carotid body
      (CB) during postnatal development in relation to physiological requirements.
      Chronic normobaric hyperoxia attenuates the carotid chemosensory response to
      hypoxia. During aging there is less of a CB response to hypoxia, which results in
      a reduced ventilatory adaptation and chemosensory discharge. To test if the
      oxygen-sensitive mechanism is affected by chronic hyperoxia in an age-dependent
      fashion, we have studied structural and ultrastructural aspects of young and old
      rat CBs. Four groups of six male Wistar rats were used. One group of two-month
      old rats and another of 25-month-old rats were kept at room air. The other two
      groups, age matched, were exposed to 98-100% O2, for 60-65 h, in a large
      Plexiglas chamber. The rats were anesthetized, CBs were fixed in situ with
      glutaraldehyde (2.5% in phosphate buffer. pH 7.4, 320 mOsm), and were prepared
      for electron microscopy. Young hyperoxic rats showed focal necrosis in type I
      cells, along with an increase of endoplasmic reticulum, Golgi apparatus, and of
      mitochondria volume, with loss of cristae. These changes were less pronounced in
      the older rat CBs compared with the young rats. In conclusion, hyperoxia seems to
      affect the oxygen-sensitive mechanism in the carotid body cells, and the reduced
      effects shown in the old rat CBs suggest an age-related decreased sensitivity to
      oxygen.

PMID- 9639169
TI  - Cohort size and maximum likelihood estimation of mortality parameters.
AB  - The purpose of this study was to investigate the effects of cohort size on
      maximum likelihood estimates of mortality parameters. Recent experimental
      investigations have stressed the importance of large cohorts for detecting
      leveling off of mortality rates at older ages. In the present study, emphasis was
      placed on evaluation of relatively small cohorts (about 150-300 individuals).
      Deaths were simulated under the assumption of the frailty mortality model. Two
      different parameter sets that resulted in differences in mean life span of more
      than twofold were used for simulations. Our smallest cohorts yielded parameter
      estimates that had generally good statistical properties, but relatively large
      standard errors. For tests of hypotheses concerning equality of parameters among
      populations or experimental treatments, empirical standard errors (obtained from
      several cohorts) were preferable to asymptotic standard errors (obtained for
      single cohorts). In particular, empirical standard errors yielded reliable type I
      error rates.

PMID- 9639171
TI  - 1st meeting of the German Interest Group for Geronto-Endocrinology.

PMID- 9639170
TI  - Analysis of the effect of membrane arachidonic acid concentration on modulation
      of glutamate release by interleukin-1: an age-related study.
AB  - Aging is associated with a change in membrane composition that includes a
      decrease in membrane polyunsaturated fatty acids, including arachidonic acid, and
      an increase in membrane cholesterol. Alterations in membrane structure are likely
      to impact on transmitter release, which relies on the fusion of synaptic plasma
      and synaptic vesicle membranes, and it may therefore be the underlying cause of
      the age-related decrease in glutamate release in hippocampal preparations. Recent
      evidence indicates that interleukin-1, by binding with its receptor, inhibits
      glutamate release in hippocampal synaptosomes prepared from young but not aged
      rats. The age-related attenuated effect may be due to impaired ligand-receptor
      interactions arising from the change in membrane composition, which should
      theoretically be reversed by increasing membrane polyunsaturated fatty acid
      concentration. To test this hypothesis, we have investigated the effect of a diet
      supplemented with arachidonic acid and its precursor, gamma-linolenic acid, on
      membrane arachidonic acid concentration, glutamate release and on the release
      response to interleukin-1 in hippocampal tissue prepared from aged and young
      rats. We report that dietary supplementation reversed the age-related changes in
      membrane arachidonic acid and expression of IL-1beta. We also present data that
      indicate that the age-related decrease in glutamate release from hippocampal
      synaptosomes was reversed in aged animals that had been fed on the experimental
      diet. The data support the view that changes in membrane composition contribute
      to certain age-related deficits, in particular the decrease in glutamate release
      observed in hippocampal synaptosomes.

PMID- 9639172
TI  - The clinical relevance of observational research.

PMID- 9639173
TI  - Analgesia in the accident and emergency department: do SHOs have the knowledge to
      provide optimal analgesia?
AB  - OBJECTIVE: To assess senior house officers' knowledge in prescribing emergency
      analgesia for acute presentations in the accident and emergency (A&E) department.
      DESIGN: Prospective telephone survey of a defined population of SHOs, using a
      standardised structured questionnaire, in the months of October and November,
      1995; 231 SHOs from 215 A&E departments were interviewed. The questionnaire
      required responses to hypothetical scenarios. A six member expert panel from the
      local region was consulted for suggestions for appropriate responses. MAIN
      OUTCOME MEASURES: Comparisons between SHO responses and those of an expert panel.
      RESULTS: For choice of analgesic agent, 83% of SHO responses were appropriate,
      for route of administration 57%, and for the dose of drug 34%. The scenario with
      the best overall response was a sprained ankle. The paediatric case with partial
      burns faired worse. Responses to a myocardial infarction scenario were the most
      consistent. CONCLUSIONS: A&E SHOs lack knowledge and confidence when asked to
      prescribe emergency analgesia for acute conditions. Responses to certain
      scenarios were extremely varied, indicating a need for national analgesia
      guidelines and protocols. Recognised training in pain management should be more
      readily available.

PMID- 9639174
TI  - Do supine oblique views provide better imaging of the cervicothoracic junction
      than swimmer's views?
AB  - OBJECTIVE: To determine whether a swimmer's view or supine (trauma) oblique views
      are more likely to visualise the lower cervical spine when a lateral view fails
      to show the cervicothoracic junction. DESIGN: A prospective study comparing two
      20 week periods. In the first phase the swimmer's view was performed as an
      additional view when the cervicothoracic junction was not demonstrated. In the
      second phase paired supine oblique views replaced the swimmer's view. RESULTS:
      230 patients were included in the first phase, of whom 60 required swimmer's
      views. In the second phase 62 of 197 patients required supine oblique views.
      Radiology analysis of 53 pairs of supine oblique views showed that the vertebral
      bodies were adequately demonstrated at the cervicothoracic junction in only 20
      patients (38%) compared with 22 in the swimmer's group (37%). The facet joints
      and posterior elements were, however, clearly seen in 37 (70%) of the supine
      oblique patients compared with 22 (37%) of the swimmer's group (p < 0.001, chi2
      test). Exposure dose calculations showed a substantial reduction for a pair of
      supine oblique views (1.6 mGy) over a single swimmer's view (7.2 mGy).
      CONCLUSIONS: In injured patients for whom the standard three view series fails to
      demonstrate the cervicothoracic junction, swimmer's views and supine oblique
      views show the alignment of the vertebral bodies with equal frequency. However,
      supine oblique films are safer, expose patients to less radiation, and are more
      often successful in demonstrating the posterior elements.

PMID- 9639175
TI  - Efficacy of transabdominal ultrasound examination in the diagnosis of early
      pregnancy complications in an emergency department.
AB  - OBJECTIVE: To assess the value of ultrasound in an emergency department in the
      diagnosis of early pregnancy complications, the efficacy of a study protocol in
      identifying ectopic pregnancies, and the agreement on ultrasound findings among
      emergency department staff and gynaecologists. METHODS: All women presenting with
      early pregnancy complications had a transabdominal ultrasound scan performed by
      the attending doctor and checked by a senior doctor. The ultrasound findings were
      classified as normal intrauterine pregnancy (IUP), probable abnormal pregnancy,
      definite ectopic pregnancy, no definite IUP, and other. Women with clinical and
      ultrasound findings compatible with threatened abortion were referred to a
      gynaecologist, or were admitted if findings suggested abnormal or ectopic
      pregnancy, or if a definite IUP could not be confirmed on ultrasound scan. For
      patients who were admitted or referred, a transvaginal ultrasound scan was
      performed by the attending gynaecologist. The findings of the gynaecologist were
      used as the gold standard. RESULTS: 151 cases were enrolled during a four month
      study period. Ultrasound findings in the emergency department included definite
      IUP in 95 (63%), probable abnormal IUP in 20 (13%), no definite IUP in 23 (21%),
      and other findings in four (3%). For evaluating the presence or absence of IUP,
      sensitivity of the initial scan was 82% (95% confidence interval 76% to 88%) and
      specificity 92% (88% to 96%). Agreement between junior and senior emergency
      department doctors on their ultrasound findings was 81% (75% to 87%) and between
      emergency department senior staff and gynecologists 85% (79% to 91%). The
      diagnoses made in the emergency department were thought to be compatible with the
      final assessments by gynaecologist in 72% (65% to 79%). Using either no definite
      IUP or other findings as a positive screening test for ectopic pregnancy, the
      sensitivity, specificity, positive predictive value, and negative predictive
      value were 80% (74% to 86%), 78% (71% to 85%), 12% (7% to 17%), and 99% (97% to
      100%), respectively. CONCLUSIONS: Transabdominal ultrasound performed in the
      emergency department is useful in screening for early pregnancy complications.
      Ectopic pregnancy should be suspected when no IUP is found on preliminary
      scanning.

PMID- 9639176
TI  - The risks of minor head injury in the warfarinised patient.
AB  - The risk factors affecting intracranial haemorrhage in warfarinised patients are
      described and an attempt made to calculate the risk of haemorrhage in
      warfarinised patients with minor head injuries. Using the data from studies of
      patients with spontaneous haemorrhage while taking warfarin, guidelines for
      treatment and given and the likely outcome predicted.

PMID- 9639177
TI  - Aerobic and anaerobic microbiology of infections after trauma in children.
AB  - OBJECTIVE: To review the recovery of aerobic and anaerobic bacteria from
      infections after trauma in children over a 20 year period. METHODS: Only
      specimens that were studied for both aerobic and anaerobic bacteria were included
      in the analysis. They were collected from seven separate centres in which the
      microbiology laboratories only accepted specimens that were properly collected
      without contamination and were submitted in appropriate transport media.
      Anaerobes and aerobic bacteria were cultured and identified using standard
      techniques. Clinical records were reviewed to identify post-trauma patients.
      RESULTS: From 1974 to 1994, 175 specimens obtained from 166 children with trauma
      showed bacterial growth. The trauma included blunt trauma (71), lacerations (48),
      bites (42), and open fractures (5). Anaerobic bacteria only were isolated in 38
      specimens (22%), aerobic bacteria only in 51 (29%), and mixed aerobic-anaerobic
      flora in 86 (49%); 363 anaerobic (2.1/specimen) and 158 aerobic or facultative
      isolates (0.9/specimen) were recovered. The predominant anaerobic bacteria
      included Peptostreptococcus spp (115 isolates), Prevotella spp (68),
      Fusobacterium spp (52), B fragilis group (42), and Clostridium spp (21). The
      predominant aerobic bacteria included Staph aureus (51), E coli (13), Ps
      aeruginosa (12), Str pyogenes (11) and Klebsiella pneumoniae (9). Principal
      infections were: abscesses (52), bacteraemia (3), pulmonary infections (30,
      including aspiration pneumonia, tracheostomy associated pneumonia, empyema, and
      ventilator associated pneumonia), wounds (36, including cellulitis, post
      traumatic wounds, decubitus ulcers, myositis, gastrostomy and tracheostomy site
      wounds, and fasciitis), bites (42, including 23 animal and 19 human), peritonitis
      (4), osteomyelitis (5), and sinusitis (3). Staph aureus and Str pyogenes were
      isolated at all sites. However, organisms of the oropharyngeal flora predominated
      in infections that originated from head and neck wounds and abscesses, and bites,
      and those from the gastrointestinal tract predominated in infections that
      originated from peritonitis, abdominal abscesses, and decubitus ulcers.
      CONCLUSIONS: Many infections that follow trauma in children involve multiple
      organisms.

PMID- 9639178
TI  - Primary care problems in patients attending a semi-rural accident and emergency
      unit: a prospective study.
AB  - OBJECTIVE: To analyse the characteristics of patients attending a coastal resort
      accident and emergency (A&E) unit and compare use by summer visitors with use by
      the indigenous winter population by previously validated assessment criteria.
      SETTING: Accident and emergency unit of a semi-rural coastal town district
      general hospital. SUBJECTS: 3643 first attenders in the summer cohort and 2876 in
      the winter cohort. METHODS: All patients attending the A&E unit over two 28 day
      periods in summer and winter 1995 were assessed prospectively in four categories
      by trained, experienced nurse assessors. Category 4 identified patients who
      fulfilled the King's College Hospital criteria as being suitable for care from
      primary care practitioners. RESULTS: 43.8% of the summer patients could have been
      seen in the primary care setting, as could 38.7% of the winter visitors.
      CONCLUSIONS: The proportion of patients with primary care problems who attend
      semi-rural A&E units appears to be much higher than previously thought. These
      findings cast doubt on the validity of the King's College Hospital criteria for
      classifying patients to either primary care or A&E categories.

PMID- 9639179
TI  - The work of the American emergency physician.
AB  - The organisation of the American emergency health care system has changed rapidly
      during recent years, but it remains very different to the system in the United
      Kingdom. American emergency departments are organised around an attending
      physician based service, rather than a consultant led service. As a result, the
      work of the American emergency physician differs considerably from that of the
      United Kingdom A&E consultant. The problems associated with working in an
      attending physician based service include antisocial hours of work, sleep
      deprivation, decreased job satisfaction, and "burn out," all in the context of a
      relatively hostile medicolegal climate. Although there appear to be no easy
      answers to some of these problems, the A&E specialist should be aware of the
      potential future difficulties for A&E medicine as it develops within the United
      Kingdom.

PMID- 9639180
TI  - A transatlantic comparison of training in emergency medicine.
AB  - The system of training in accident and emergency (A&E) medicine in the United
      Kingdom is at a critical and much earlier stage of development than in the United
      States. Transatlantic comparison offers the opportunity to explore possible ways
      of improving training in the United Kingdom. Comparison revealed deficiencies in
      the UK training system in the following: prehospital care training, formal
      theoretical teaching, close supervision in a clinical setting, and in-service
      training examinations. Implementation of measures designed to address these
      deficiencies would enhance UK training in A&E medicine.

PMID- 9639181
TI  - Accident and emergency 24 hour senior cover--a necessity or a luxury?

PMID- 9639182
TI  - The flat electrocardiogram--systole or asystole?
AB  - A case of stone heart syndrome is reported in a pregnant 27 year old West African
      patient, who suffered syncopal symptoms shortly before cardiac arrest. The
      electrocardiographic features were those of asystole, but direct examination of
      the heart at emergency thoracotomy in the A&E department revealed tetanic
      contracture of the organ. At necropsy, the heart was of normal weight but showed
      areas of fibrosis surrounding the bundle of His. The discrepancy between the ECG
      features and the physiological state of the heart raises the possibility that
      other cases of apparent asystole may not be what they seem.

PMID- 9639183
TI  - Spontaneous carotid artery dissection presenting as migraine--a diagnosis not to
      be missed.
AB  - Two cases are reported in which the diagnosis of a serious condition was delayed
      as the symptoms had been attributed to migraine. Spontaneous carotid artery
      dissection is a serious but treatable cause of headache that may be misdiagnosed
      as recent onset migraine. The importance of correctly identifying this condition
      is emphasised.

PMID- 9639184
TI  - Late clotted haemothorax after blunt chest trauma.
AB  - A clotted haemothorax can develop any time after blunt chest trauma. Two cases
      are described in which late clotted haemothoraces developed which were treated by
      limited thoracotomy and evacuation of clots. Late clotted haemothorax may occur
      even in the absence of any abnormal initial clinical findings. Early detection
      and treatment is important to avoid the complications of fibrothorax and empyema
      with permanent pulmonary dysfunction. After blunt chest trauma patients should be
      advised to return to the accident and emergency department for assessment on
      development of any new chest symptom. Under these circumstances a chest x ray is
      mandatory to exclude a haemothorax.

PMID- 9639185
TI  - Out of hospital cardiac arrest and associated injury.
AB  - Three patients are described who sustained injuries around the time of a collapse
      that led to out of hospital cardiac arrest. In this group of patients the
      importance of taking a complete medical history and recording the circumstances
      of the syncopal episode cannot be overemphasised. If cardiac output is
      successfully restored the possibility of occult traumatic injury must be
      considered in high risk patients.

PMID- 9639186
TI  - Ectopic pregnancy presenting with obturator nerve pain.
AB  - A 27 year old woman had a three day history of pain in the cutaneous distribution
      of the left obturator nerve before she developed the classical picture of ectopic
      pregnancy with lower abdominal pain and vaginal bleeding. A left tubal pregnancy
      was subsequently confirmed by laparoscopy. Referred pain along the obturator
      nerve has been reported in other pelvic conditions, but has not previously been
      reported as a manifestation of ectopic pregnancy. Ectopic pregnancy may present
      with a very wide range of signs and symptoms and should be excluded in females of
      child bearing age with unexplained symptoms including pain anywhere from the
      shoulder down to the knee.

PMID- 9639187
TI  - Clarithromycin induced digoxin toxicity.
AB  - A case of digoxin poisoning following the co-administration of digoxin and
      clarithromycin in a 28 year old male is described. Since the aetiology of chronic
      digoxin poisoning is often unclear, clinicians should be aware of the potential
      drug-drug interaction between digoxin and clarithromycin.

PMID- 9639188
TI  - Caffeine toxicity in a bodybuilder.
AB  - Substance abuse is well documented among bodybuilders and weight lifters keen to
      enhance their performance. A case is described of abuse of caffeine to toxic
      levels by an amateur bodybuilder and is believed to be the first documented case
      of such recreational abuse.

PMID- 9639189
TI  - A case of ipsilateral shoulder and elbow dislocation: an easily missed injury.

PMID- 9639190
TI  - Spinal tumour: a diagnostic lesson.

PMID- 9639191
TI  - Accident and emergency broadsheet: Undergraduate accident and emergency medicine
      education broadsheet.

PMID- 9639192
TI  - Purchasing new equipment.

PMID- 9639193
TI  - Disciplinary procedures.

PMID- 9639194
TI  - Is routine computed tomographic (CT) scanning necessary in suspected basal skull
      fractures?

PMID- 9639195
TI  - Anaesthetic for Colles' fracture.

PMID- 9639196
TI  - Sevoflurane.

PMID- 9639197
TI  - Traumatic pericardial tamponade.

PMID- 9639198
TI  - SHOs' interpretation of x rays.

PMID- 9639199
TI  - Curriculum based teaching.

PMID- 9639200
TI  - Developments in radiology.

PMID- 9639201
TI  - Significance of asymptomatic microhaematuria in men.

PMID- 9639202
TI  - Clinical guidelines and standards for the management of uncomplicated genital
      chlamydial infection. Central Audit Group in Genitourinary Medicine.

PMID- 9639203
TI  - Attitudes to HIV testing in general practice.
AB  - Newer therapies for the treatment of HIV infection and the effectiveness of
      zidovudine in reducing vertical transmission mean that it is becoming
      increasingly important to diagnose HIV infection earlier. General practitioners
      (GPs) attending a local study day on sexually transmitted diseases (STDs) were
      asked about their likelihood of raising the subject of HIV antibody testing, and
      their anxiety when doing so, for different patient groups. A high level of
      anxiety was found when raising this topic in certain patient groups, and a
      proportion of GPs would never discuss HIV testing, even in very high-risk groups.
      No respondents were aware that vertical transmission could be reduced by
      antiretroviral drug therapy. These data advocate that the barriers to raising the
      issue of HIV testing and the methods of reducing GPs' anxiety associated with it,
      need to be addressed.

PMID- 9639204
TI  - Systemic immunosuppression by HIV infection influences HPV transcription and thus
      local immune responses in condyloma acuminatum.
AB  - Human immunodeficiency virus (HIV) infection is considered to influence the
      pathogenesis of human papillomavirus (HPV)-associated diseases. It is not clear
      whether this occurs directly through molecular interactions between viral genes
      and/or indirectly through effects on the immune functions. In the present study
      we compared molecular characteristics of penile condylomas from immunocompetent
      and HIV-positive individuals. Using polymerase chain reaction (PCR) and reverse
      transcriptase (RT)-PCR techniques we determined some characteristics of local
      immune responses and transcriptional activity of both viruses. Our findings
      revealed that HIV-seropositivity was accompanied by multiple HPV infection and a
      CD4-count-dependent appearance of oncogenic HPV-types. HIV infection also changed
      the patterns of HPV transcription favouring transcription of early genes such as
      E7. Apparently, HIV infection influences local immunity by altering HPV
      transcription and by systemic immunodeficiency.

PMID- 9639205
TI  - Condom use among Aboriginal people in Ontario, Canada.
AB  - A survey of 658 Aboriginal men and women living in 11 reserve communities in
      Ontario, Canada, was utilized to collect data on patterns of condom use.
      Individuals who had sexual intercourse in the previous 12 months were included in
      the analysis (n=400). Descriptive statistics and multiple logistic regression
      were used to analyse condom use in the previous 12 months. Eight per cent always,
      31% sometimes, and 61% never used condoms. Rates of condom use differed with the
      number of sex partners in the last year, age, gender, having a steady sex
      partner, and marital status. Multiple logistic regression revealed that people
      most likely to use condoms were under the age of 30, male, did not have a long
      term steady sex partner, had more than one sex partner, worried about pregnancy,
      were knowledgeable about HIV/AIDS, and were not embarrassed to obtain condoms.
      Condom users who were knowledgeable about HIV/AIDS and who knew someone with
      HIV/AIDS were more likely to always use condoms. The most common reason for not
      using a condom was 'I was with my steady sex partner'. These results have
      implications for STD prevention efforts and for future research of sexual and STD
      preventive behaviour among Aboriginal people.

PMID- 9639206
TI  - Hospital service interventions and improving survival of AIDS patients St Mary's
      Hospital, London, 1982-1991.
AB  - The relationship between changes in hospital service interventions at St Mary's
      Hospital, London, reduced case fatality for patients with their first episode of
      Pneumocystis carinii pneumonia (PCP) and improved survival from diagnosis of AIDS
      was investigated for the period 1982-1991. Multivariate logistic regression
      models identified factors independently associated with episode survival; for
      those patients who survived their first episode of PCP, survival from time of
      diagnosis of AIDS was analysed using multivariate Cox's proportional hazards
      models. The case-fatality rate after 1987 was significantly lower for the 159
      subjects. Median survival from diagnosis of AIDS increased significantly from 142
      days to 554 days (P=0.01). Improved survival of first episode of PCP was
      associated with it being the index diagnosis and having a haemoglobin at
      diagnosis of PCP greater than 12 g/dl. The presence of a concurrent AIDS-defining
      condition in patients who presented with an A-a gradient equal to or greater than
      40 mmHg was associated with reduced episode survival, especially before 1987. For
      the 126 individuals who survived their first episode of PCP, death rates were
      lowest in patients treated with primary or secondary PCP prophylaxis and those
      who received zidovudine since their first episode of PCP. Survival in patients
      with HIV disease is better in patients who receive appropriate antiretroviral
      treatment of HIV infection and timely treatment of opportunistic illnesses. Early
      diagnosis of HIV-1 infection with early diagnosis and treatment of first episode
      of PCP was associated with improved episode survival. Subsequent medical follow
      up combined with PCP prophylaxis and zidovudine were significantly associated
      with long-term survival.

PMID- 9639207
TI  - Sexually transmitted disease rates before and after HIV testing.
AB  - The aim of the study was to evaluate the effect of having an HIV-positive or
      negative test result on sexual risk behaviour before and after the test.
      Longitudinal retrospective case-note survey identifying new episodes of sexually
      transmitted disease (STD) infections in 114 subjects testing HIV positive and 114
      matched negatives were examined at the Genitourinary Medicine Department, St
      Mary's Hospital, Paddington, London. Across the whole sample in the year after
      HIV testing the number of cases of new STD infections was 40% of the number of
      cases in the year prior to HIV testing. There was no association between
      serostatus and incidence of STD infections before and after HIV testing. Of those
      testing negative, 5.3% were identified as having a new infection in the year
      after the HIV test, while amongst those testing positive there was a rate of new
      STDs of 2.6%. In conclusion, there was no evidence that having a negative test
      result increased the risk of acquisition of new STDs. Rates of new STD infections
      amongst seropositives in the year after HIV testing were low.

PMID- 9639208
TI  - HIV, STDs, anal sex and AIDS prevention policy in a northeastern Brazilian city.
AB  - Data on HIV/AIDS, other STDs, and related sexual practices and AIDS prevention
      measures in Sao Luis, capital of Maranhao state, were collected in May-July 1995
      using participant-observation fieldwork, including a number of face-to-face
      interviews in addition to archival research, and were updated by correspondence
      in 1996-1997 and a brief visit in February 1998. In contrast to the continuing
      severe AIDS epidemic in southern Brazil, public health statistics and public HIV
      testing recently instituted in Sao Luis suggest that HIV infection has remained
      largely concentrated among men who have sex with men, as well as a few, though
      growing number of cases of women evidently infected by such men. However, other
      STDs are endemic to the region, and could provide an increasing portal of entry
      for HIV infection. AIDS prevention education programmes have commenced in public
      schools and elsewhere in Sao Luis, but greater emphasis needs to also be placed
      on the prevention and treatment of other STDs. As in other regions of Brazil and
      Latin America, the reportedly common practice of anal sex among heterosexuals
      also represents a significant yet typically underemphasized risk factor for HIV.

PMID- 9639209
TI  - Outcome of inflammatory smears managed in a genitourinary medicine clinic.

PMID- 9639210
TI  - An audit of cervical cytological screening amongst HIV-positive women.

PMID- 9639211
TI  - Cervical smear: is screening of teenagers justified?

PMID- 9639212
TI  - Charter mark for genitourinary medicine.

PMID- 9639213
TI  - Genitourinary medicine services in Manchester Royal Infirmary.

PMID- 9639214
TI  - Occult anal sphincter trauma following randomized forceps and vacuum delivery.
AB  - OBJECTIVE: To determine the prevalence of occult anal sphincter trauma 5 years
      after randomization to forceps and vacuum delivery. METHOD: Anal endosonography
      and manometry was performed in 44 of 313 women who had originally participated in
      one center of the Keele University Multicenter Assisted Delivery Trial at the
      North Staffordshire Maternity Hospital between September 1989 and May 1990.
      RESULTS: 50% admitted to defecatory symptoms and anal sphincter defects were
      identified in 61%. On the basis of intention to treat, 82% of forceps (n = 17)
      and 48% of vacuum deliveries (n = 27) had occult sphincter defects (P = 0.03). In
      four women, both instruments were used. However, the preponderance of defects in
      the forceps group persisted even when analysis was performed according to the
      final mode of delivery as well as in the group where only one instrument was used
      (n = 40). There was a significant fall in maximum squeeze anal pressure in the
      forceps group compared to the vacuum group (56 vs. 36 mmHg; P = 0.0007). Although
      twice as many in the forceps group suffered anal incontinence (32% vs. 16%)
      significance was not reached. CONCLUSIONS: Vacuum delivery appears to be
      associated with less occult anal sphincter trauma than forceps delivery. A large
      prospective randomized study is required to address the impact of specific
      situations, such as failed instrumentation with use of a second instrument and
      rotational delivery.

PMID- 9639215
TI  - Second trimester calcium-phosphorus-magnesium homeostasis in women with
      threatened preterm delivery.
AB  - OBJECTIVE: The effect of threatened preterm delivery on calcium, phosphorus,
      magnesium homeostasis in the second trimester of pregnancy was investigated.
      METHODS: Serum concentrations of total and ionized calcium, inorganic phosphorus,
      magnesium, total protein, albumin, total estrogens and human placental lactogen
      were determined in women with threatened preterm delivery at 23-28 weeks of
      gestation (the studied group) and in women with uncomplicated pregnancy of the
      same duration (the control group). Additionally activities of total alkaline
      phosphatase and heat-stable alkaline phosphatase fraction were measured. RESULTS:
      Patients of the studied group compared to the control group showed decreased
      concentration of total calcium (2.15 +/- 0.073 vs. 2.25 +/- 0.11 mmol/l, P <
      0.001), inorganic phosphorus (1.21 +/- 0.26 vs. 1.34 +/- 0.22 mmol/l, P < 0.01)
      and magnesium (0.63 +/- 0.053 vs. 0.71 +/- 0.12 mmol/l, P < 0.001), total protein
      (64.0 +/- 5.4 vs. 68.6 + 1.0 g/l, P < 0.001), albumin (546.3 +/- 55.1 vs. 579.6
      +/- 49.3 micromol/l, P < 0.003) and placental lactogen (3664 +/- 1806 vs. 4651 +/
      1858 ng/ml, P < 0.02); they also demonstrated decreased activity of total
      alkaline phosphatase (42.17 +/- 16.99 vs. 50.66 +/- 6.56 IU/l, P < 0.001) and its
      heat stable fraction (22.65 +/- 7.89 vs. 31.89 +/- 9.09 IU/l, P < 0.001).
      Patients of the studied group showed normal values of ionized calcium and total
      estrogens. CONCLUSIONS: Premature uterine contractility in women in the second
      trimester is accompanied by lowered serum concentrations of total calcium,
      inorganic phosphorus, magnesium, total protein and albumin. There is also
      decreased activity of total alkaline phosphatase, its heat-stable fraction and
      placental lactogen which may have diagnostic value. Premature uterine
      contractility in women in the second trimester may be related to the disturbances
      of calcium-phosphorus-magnesium homeostasis and calcium supplementation should be
      considered.

PMID- 9639216
TI  - Intensification of fetal and maternal surveillance in pregnant women with
      hypertensive disorders.
AB  - OBJECTIVE: To examine the need to intensify fetal and maternal surveillance in
      pregnant women with mild pregnancy hypertension. METHODS: The multi-center cohort
      study in 2413 healthy nulliparae analyzed differences in hypertension-related
      adverse events (small-for-gestational age, perinatal mortality, eclampsia,
      abruptio placentae and HELLP syndrome) according to maximum diastolic blood
      pressure and proteinuria. RESULTS: Compared to the reference group (diastolic
      blood pressure 70-85 mmHg) (n = 1882) the relative risks of adverse fetal and
      maternal outcome in 34 proteinuric hypertensive women were 8.9 (95% CI 3.3-24.1)
      and 41.5 (95% CI 9.7-178.4), respectively. In 203 non-proteinuric women with a
      maximum diastolic blood pressure of > or = 95 mmHg only the relative risk of
      adverse maternal outcome was increased (11.6, 95% CI 3.1-42.8), but it was not
      increased in 230 non-proteinuric women with a maximum diastolic of 90 mmHg.
      CONCLUSIONS: Intensified surveillance in women with mild pregnancy hypertension
      is not indicated and should be reserved for groups with increased fetal and
      maternal risk.

PMID- 9639217
TI  - Amnioinfusion in labor induction of term pregnancies with premature rupture of
      the membranes and low amniotic fluid.
AB  - OBJECTIVE: To analyze the utility of prophylactic amnioinfusion in term
      pregnancies with PROM and a low amniotic fluid index during labor induction.
      METHOD: Forty-two women with amnioinfusion and 42 in a control group with
      amniotic fluid index (AFI) below 10 cm when admitted to labor induction were
      studied. All patients had electronic fetal heart rate and intrauterine pressure
      continuous monitoring. Amnioinfusion of normal saline (37 degrees C) was realized
      in the study group, using a continuous perfusion pump at 600 ml/h for 1 h, after
      which the AFI was again recorded; if this was < 15, the perfusion was continued
      at 180 ml/h until full cervical dilatation was achieved or until uterine baseline
      activity reached 20 mm Hg. The control group received identical obstetric care
      except in respect of amnioinfusion. RESULT: Both groups were similar in age,
      primiparity, gestational age, initial AFI, interval from rupture of membranes
      until delivery and length of labor. The amnioinfusion of 600 ml in 1 h
      significantly increased the AFI (an increase of 7.2 +/- 3.9 vs. a decrease of 1.1
      +/- 1.6, P < 0.01). In the amnioinfusion group, there was a significantly lower
      rate of cesarean deliveries (0 vs. 6, P < 0.05) and a better mean umbilical
      arterial pH at delivery (7.24 +/- 0.07 vs. 7.21 +/- 0.08, P < 0.05). No
      differences were observed in maternal or neonatal hospitalization days or
      infectious morbidity. CONCLUSION: It is concluded that prophylactic amnioinfusion
      improves neonatal metabolic state when used in labor induction of term
      pregnancies with PROM and a low amniotic fluid index.

PMID- 9639218
TI  - Effects of postpartum corticosteroids in patients with HELLP syndrome.
AB  - OBJECTIVE: To evaluate the effect of corticosteroid treatment on the postpartum
      recovery of parturients with HELLP syndrome. METHOD: Thirty cases with HELLP
      syndrome were randomly assigned to a study or a control group, each including 15
      patients. A total dose of 30 mg intravenous dexamethasone was given to the study
      group during the 36 h following the childbirth, while the control group did not
      receive any steroid medication. Arterial blood pressure, urine output, hematocrit
      ratio, platelet count, serum alanine and aspartate aminotransferases and uric
      acid levels were monitored during the first 48 h postpartum. The data were
      analyzed by unpaired t-test, chi2 or Fisher's exact tests. RESULT: Before the
      treatment, no significant difference was observed between the two groups. The
      study group showed statistically significant improvement in mean arterial blood
      pressure, mean serum aspartate aminotransferase level, mean urine volume per hour
      and mean platelet count (P < 0.05). Length of hospitalization was also shorter in
      the study group (P < 0.01). CONCLUSION: Early postpartum high-dose corticosteroid
      treatment accelerates the recovery and shortens the hospitalization of the
      parturients with HELLP syndrome.

PMID- 9639219
TI  - Fluorescence microsatellite analysis to study the parental origin of the
      supernumerary chromosome in Down's syndrome.
AB  - OBJECTIVE: Down's syndrome (DS) is an important cause of mental retardation. This
      study investigated the parental origin of the extra chromosome 21 in DS patients.
      METHODS: Fourteen families each with a DS patient were recruited for analysis of
      nine microsatellite markers on chromosome 21. We collected DNA from both parents
      and the patient and used polymerase chain reaction to amplify nine segments on
      chromosome 21: D21S1435, D21S1436, D21S1437, D21S1446, D21S156, D21S258, D21S263,
      D21S265 and D21S270. One of each pair of DNA primers was labeled with a
      fluorescence dye. The amplified products were subjected to electrophoresis in a
      semi-automated DNA sequencer and then analyzed with Genescan software to
      determine the origin of the extra chromosome 21. RESULTS: The extra chromosome 21
      originated from the mother in 13 (93%) patients and from the father in one (7%)
      patient. CONCLUSIONS: Our findings were compatible with those from Caucasian
      patients. A great majority of Down's syndrome cases resulted from meiotic errors
      in the eggs.

PMID- 9639220
TI  - Maternal and perinatal outcomes of multiple pregnancy following IVF-ET.
AB  - OBJECTIVE: To analyze the course of pregnancy and perinatal outcome in 31 twins,
      22 sets of triplets and five quadruplet clinical pregnancies following
      conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection
      (ICSI) procedures and in relation to 58 singleton pregnancy following the same
      procedure. METHODS: Retrospective analysis of maternal and neonatal medical
      records of 58 singleton, 31 twin, 22 triplet and five quadruplet pregnancies
      diagnosed at 7-8 weeks gestation following 561 embryo transfer procedures in 628
      oocyte collections at the IVF Center in the Maternity Hospital, Kuwait from July
      1994 to December 1996. RESULTS: The clinical pregnancy rate in 628 cycles
      proceeding to oocyte collection was 32.6%, there being 58 singletons (50.6%), 31
      twins (33.5%), 22 triplets (10.8%) and five quadruplets (2.5%). Early complicated
      outcomes included 47 miscarriages (23.7%), four ectopic pregnancies (1.9%) and
      one hydatidiform mole. The spontaneous fetal reduction rate was 20.6% in twin,
      45.5% in triplet and 40% in quadruplet pregnancies. There was a significantly
      higher maternal and neonatal complication rate in the triplet group compared to
      singletons and twins, including threatened miscarriage, pre-eclampsia, antepartum
      hemorrhage, longer hospital stay and preterm labor. The chance of operative
      delivery was higher in high-order multiple pregnancy (HOMP). The major neonatal
      complications were related to prematurity. Neonatal morbidity and mortality were
      significantly higher in the triplet group. The need for admission to the Special
      Care Baby Unit (SCBU) and the Neonatal Intensive Care Unit (NICU) was
      significantly higher in HOMP. However, there were no statistically significant
      differences in the perinatal mortality in relation to the degree of HOMP.
      CONCLUSION: Maternal complications, perinatal and neonatal morbidity after 2
      years activities in the IVF Center have been reviewed leading to changes in
      policies of management, notably a reduction in the number of embryos transferred.

PMID- 9639221
TI  - Simplified abdominal wall-lifting device for gasless laparoscopy.
AB  - OBJECTIVE: To develop a simplified abdominal wall-lifting device for gasless
      laparoscopy. METHODS: The device is composed of an electric-power actuator,
      sliding arm and abdominal wall-retractor. All parts of the device are reusable.
      The device provides planar displacement of the anterior abdominal wall to enable
      space for laparoscopy. The valveless ports and conventional instruments, as well
      as laparoscopic instruments, were used without a gas leak problem. RESULTS: After
      preliminary success in the laboratory testing, a petition was made to the
      hospital's Ethic Committee. Since then we have performed 40 gasless laparoscopic
      procedures including 13 salpingo-oophorectomies, 10 diagnostic laparoscopies,
      five tubal ligations, five ovarian cystectomies, four salpingectomies, two
      removals of pelvic IUDs and one laparoscopic hysterectomy. There were no surgical
      complications, including no abdominal wall trauma. The operative field was almost
      the same as that of the pneumoperitoneum technique, with the exception of
      morbidly obese patients. CONCLUSIONS: This preliminary experience demonstrates
      the efficiency of the simplified abdominal wall-lifting device and the potential
      advantages of gasless laparoscopy. Continued modifications and applications are
      necessary to delineate the full range of benefits of this device and technique,
      especially in developing countries.

PMID- 9639222
TI  - Oral glucose challenge effects on growth and sex steroid hormones in normal women
      and women with hypothalamic amenorrhea.
AB  - OBJECTIVE: To investigate the effect of growth hormone (GH) on the serum levels
      of ovarian and adrenal sex steroid hormones in women with hypothalamic amenorrhea
      (HA). METHODS: A standard 75-g oral glucose tolerance test (OGTT) was performed
      in 12 normal women and 16 women with stress-related or weight-loss-related
      amenorrhea. RESULTS: Significant progressive declines in GH, testosterone (T),
      estradiol (E2) and dehydroepiandrosterone sulfate (DHEAS) were observed during
      the OGTT in the normal and HA groups. Significant positive correlations were
      observed between GH and T, E2 and DHEAS. The area under the curve (AUC) for the
      GH response was significantly greater in the HA group than in the normal group.
      The ratio of the AUC of insulin-like growth factor to that of GH was
      significantly lower in the HA group. CONCLUSIONS: Growth hormone may modify
      ovarian and adrenal sex steroidogenic responses to tropic hormones. A significant
      degree of GH resistance exists in HA patients. This GH resistance may be related
      to an ovulatory disturbance.

PMID- 9639223
TI  - A maternity waiting home experience in Zimbabwe.

PMID- 9639224
TI  - Jaundice induced by hyperemesis gravidarum.

PMID- 9639225
TI  - Cessation of drug use and infant birth weight.

PMID- 9639226
TI  - Elective Shirodkar procedure: prognostic factors and postoperative pregnancy
      outcome.

PMID- 9639227
TI  - Acrania, MTHFR 677C-->T mutation and role of folate intake.

PMID- 9639228
TI  - Leiomyomatosis peritonealis disseminata.

PMID- 9639229
TI  - ACOG educational bulletin. Antiphospholipid syndrome. Number 244, February 1998.
      American College of Obstetricians and Gynecologists.

PMID- 9639230
TI  - ACOG committee opinion. Role of loop electrosurgical excision procedure in the
      evaluation of abnormal Pap test results. Number 195, November 1997. Committee on
      Gynecologic Practice. American College of Obstetricians and Gynecologists.

PMID- 9639231
TI  - ACOG committee opinion. Vitamin A supplementation during pregnancy. Number 196,
      January 1998 (replaces No. 157, September 1995). Committee on Obstetric Practice.
      American College of Obstetricians and Gynecologists.

PMID- 9639232
TI  - ACOG criteria set. Quality evaluation and improvement in practice. Tocolysis.
      Number 31, February 1998. Committee on Quality Assessment. American College of
      Obstetricians and Gynecologists.

PMID- 9639233
TI  - Behavioral tolerance to and withdrawal from multiple fluoxetine administration.
AB  - The objective of this study was to characterize the lasting effects of fluoxetine
      on the locomotor behavior of rats using a computerized activity-monitoring
      system. Challenge dosages (8, 16, and 24 mg/kg i.p.) of fluoxetine 2 h into the
      dark phase resulted in dose-dependent suppression of locomotor activity for 4 h
      following injection. Escalating (10-30 mg/kg i.p.) semidaily fluoxetine
      administration for the next five days resulted in decreasing locomotor activity
      during the multiple-administration period relative to saline control. Circadian
      activity patterns at the conclusion of the regimen were unchanged in shape, but
      featured uniform decreases in locomotor activity at every hour which were more
      significant during the phase. Upon discontinuation, fluoxetine-treated rats
      showed a significant increase in activity during the first 4 h following the
      first "missed" dose which was not seen in subsequent washout. Ninety-six h after
      the final maintenance dose, the initial three dosages were readministered, and
      the locomotor activity suppression in response to the rechallenge dose of
      fluoxetine was significantly lessened compared to initial challenge. These
      findings suggest that tolerance and withdrawal were obtained.

PMID- 9639234
TI  - Crossed cerebro-cellular diaschisis in a patients with melas with aphasia but
      without hemiparesis.
AB  - We describe a 25 year old woman diagnosed with MELAS during an acute stroke-like
      episode. Global aphasia, migraine-like headaches and hemi-anopsia were her main
      clinical features. MR imaging revealed extensive cortical and subcortical left
      hemispheric signal abnormalities. [Tc-99m]ECD SPECT scanning revealed crossed
      cerebrocerebellar diaschisis. Aphasia in the absence of gross hemiparesis can be
      related to cross-cerebellar diaschisis in MELAS.

PMID- 9639235
TI  - Acoustic startle electromyographic (EMG) activity indexed from an
      electroculographic (EOG) electrode placement: a methodological note.
AB  - Acoustic startle EMG responses were indexed from a traditional EOG electrode
      placement in 11 young adults while they viewed slides which varied in affective
      valence. We found, replicating earlier work that subjects' startle responses
      became more augmented as the content of the slides became more negative. The
      advantages of using an EOG electrode placement for measuring acoustic startle
      responses are discussed.

PMID- 9639236
TI  - Is backward stepping over obstacles achieved through a simple temporal reversal
      of forward stepping?
AB  - The main purpose of the study was to examine whether backward stepping over
      obstacles was a simple temporal reversal of kinematic and muscle activation
      patterns found in forward obstacle avoidance. Obstacle avoidance was used as a
      probe to represent one aspect of walking over variable terrain. Kinematics,
      trajectories and muscle activation profiles for forward versus backward stepping
      over obstacles revealed that the simple reversal of locomotor patterns observed
      for level walking cannot be applied to obstacle avoidance. However, key kinematic
      data and limb trajectories for backward leading limb stepping were found to be
      similar to existing forward trailing limb data. Therefore, it appears that
      stepping over obstacles requires a complex upper level reorganization of the
      basic locomotor pattern based on biomechanical and sensory feedback.

PMID- 9639237
TI  - Utility of the seven subtest WAIS-R short form in a female sample with brain
      damage.
AB  - We examined the accuracy of the WAIS-R seven subtest short form (Ward, 1990) for
      predicting IQs of 130 females with brain damage or dysfunction. Means for age,
      education, and FSIQ were 44.37 years (SD = 18.46), 12.74 years (SD = 2.42), and
      87.64 (SD = 13.62). Results indicated that 93%, 84%, and 93% of short form
      estimated VIQs, PIQs, and FSIQs were within +/-5 points of their actual WAIS-R
      scores. In terms of Wechsler's (1981) seven category intelligence classification,
      levels of agreement were 83%, 72%, and 82% for the Verbal, Performance, and Full
      scales, respectively. These findings support the use of the seven subtest short
      form with brain-damaged women when time is at a premium and only a general
      estimate of intellectual functioning is required.

PMID- 9639238
TI  - Smell and taste of chewing gum affect frequency domain EEG source localizations.
AB  - We investigated brain electric field signatures of subjective feelings after
      chewing regular gum or gum base without flavor. 19-channel eyes-closed EEG from
      20 healthy males before and after 5 minutes of chewing the two gum types in
      random sequence was source modeled in the frequency domain using the FFT-Dipole
      Approximation. 3-dimensional brain locations and strengths (Global Field Power,
      GFP) of the equivalent sources of five frequency bands were computed as changes
      from pre-chewing baseline. Gum types differed (ANOVA) in pre-post changes of
      source locations for the alpha-2 band (to anterior and right after regular gum,
      opposite after gum base) and beta-2 band (to anterior and inferior after regular
      gum, opposite after gum base), and of GFP for delta-theta, alpha-2 and beta-1
      (regular gum: increase. gum base: decrease). Subjective feeling changed to more
      positive values after regular gum than gum base (ANOVA).--Thus, chewing gum with
      and without taste-smell activates different brain neuronal populations.

PMID- 9639239
TI  - ATP-sensitive potassium channels mediate norepinephrine- and morphine-induced
      antinociception at the spinal cord level.
AB  - The effects of intrathecally (i.t.) administered glibenclamide, a blocker of
      adenosine triphosphate-sensitive potassium ( KATP) channels, on antinociception
      produced by i.t. norepinephrine, morphine, or 5'-N-ethylcarboxamide adenosine, an
      adenosine agonist, were investigated using tail-flick assay. The results showed
      that: 1) i.t. norepinephrine (1 nmol), morphine (0.5 nmol) and 5'-N
      ethylcarboxamide adenosine (0.5 nmol) elicited prolongation of tail-flick
      latency, 2) i.t. glibenclamide given in 2 different doses (5 and 10 nmol)
      exhibited no effects on tail-flick latency, 3) the antinociception produced by
      norepinephrine (1 nmol) and morphine (0.5 nmol) was blocked by glibenclamide in a
      dose-dependent manner, 4) glibenclamide failed to modulate the effects of 5'-N
      ethylcarboxamide adenosine on tail-flick latency. These observations suggest that
      KATP channels may play an important role in norepinephrine- and/or morphine
      induced antinociception at the spinal level.

PMID- 9639240
TI  - Using event-related potentials to examine pharmacological effects on intervening
      cognitive functions in rats.
AB  - Assessing toxicological and pharmacological effects on cognition using sensory
      evoked potentials and purposive behaviors as endpoints may limit testing to
      afferent activity and to populations able to follow directions. The present study
      uses a non-invasive method that does not require training or response to
      instruction to measure the brain's longer latency intervening cognitive response
      to stimulation. The averaged electrophysiological responses of 8 rat brains,
      Event-Related Potentials (ERPs), were recorded in 3 spatial dimensions and time
      while they experienced two time varying modes of auditory stimulation and
      anesthesia. Results show that both modes of stimulation elicited ERPs with
      similar magnitudes and latencies but with different electrophysiological patterns
      at each level of anesthesia. These results suggest anesthesia may not effect the
      brain's ability to detect and represent an input, but rather its ability to
      inhibit that input's decay over time so it can consolidate into a form able to
      benefit future processing. Anesthesia effected these events during the two modes
      of stimulation differently over time, suggesting this method of stimulation and
      recording may provide dependent variables sensitive to the brain's response at
      different dose levels.

PMID- 9639241
TI  - Treatment with AC pulsed electromagnetic fields normalizes the latency of the
      visual evoked response in a multiple sclerosis patient with optic atrophy.
AB  - Visual evoked response (VER) studies have been utilized as supportive information
      for the diagnosis of multiple sclerosis (MS) and may be useful in objectively
      monitoring the effects of various therapeutic modalities. Delayed latency of the
      VER, which reflects slowed impulse transmission in the optic pathways, is the
      most characteristic abnormality associated with the disease. Brief transcranial
      applications of AC pulsed electromagnetic fields (EMFs) in the picotesla flux
      density are efficacious in the symptomatic treatment of MS and may also
      reestablish impulse transmission in the optic pathways. A 36 year old man
      developed an attack of right sided optic neuritis at the age of 30. On
      presentation he had blurring of vision with reduced acuity on the right and
      fundoscopic examination revealed pallor of the optic disc. A checkerboard pattern
      reversal VER showed a delayed latency to right eye stimulation (P100 = 132 ms;
      normal range: 95-115 ms). After he received two successive applications of AC
      pulsed EMFs of 7.5 picotesla flux density each of 20 minutes duration
      administered transcranially, there was a dramatic improvement in vision and the
      VER latency reverted to normal (P100= 107 ms). The rapid improvement in vision
      coupled with the normalization of the VER latency despite the presence of optic
      atrophy, which reflects chronic demyelination of the optic nerve, cannot be
      explained on the basis of partial or full reformation of myelin. It is proposed
      that in MS synaptic neurotransmitter deficiency is associated with the visual
      impairment and delayed VER latency following optic neuritis and that the recovery
      of the VER latency by treatment with pulsed EMFs is related to enhancement of
      synaptic neurotransmitter functions in the retina and central optic pathways.
      Recovery of the VER latency in MS patients may have important implications with
      respect to the treatment of visual impairment and prevention of visual loss.
      Specifically, repeated pulsed applications of EMFs may maintain impulse
      transmission in the optic nerve and thus potentially sustain its viability.

PMID- 9639242
TI  - A neuromagnetic view of hippocampal memory functions.
AB  - Bursts of highly synchronized discharges of 4-7Hz sinusoidal wave activity can be
      recorded from the hippocampus during rapid eye movement (REM) sleep. These
      rhythmic discharges, the hippocampal theta activity, are generated in the dentate
      granule cells and the pyramidal cell layers of the CA1 field of the hippocampus.
      The physiological function of the hippocampal theta activity is elusive. The
      occurrence of this rhythm throughout the REM sleep stage suggests that it is
      related to some fundamental neurophysiological phenomena associated with REM
      sleep, particularly consolidation of memory processes. Synchronous oscillations
      among a population of neurons are expected to yield stronger, more coherent
      associated magnetic fields which, through their influence back on the electrical
      fields via induction, would exert an independent effect on the electrical
      activity of hippocampal neurons and additionally, could foster and reinforce
      these oscillations through self-induction. The snail-shaped structure of the
      hippocampal formation, which resembles a solenoid embedded in the temporal lobe,
      would be expected to amplify these magnetic fields. Additionally, the discovery
      of large ferromagnetic particles in the human hippocampus suggests that it may
      function as a large iron-core electromagnet. It is proposed that memory traces
      may be encoded or decoded magnetically and analogous to a videotape, each
      encoding unit (i.e., synapse, set of synapses or glial cell) could be magnetized
      in one direction, or the other through the flow of a strong, AC magnetic field
      along the hippocampal formation. The encoding of memory traces in the hippocampal
      formation may ultimately reflect an electromagnetic phenomenon.

PMID- 9639243
TI  - Age-dependent effect of ketanserin on the sleep-waking phases in rats.
AB  - The age-dependent effect of the specific 5-HT2 receptor antagonist ketanserin at
      two doses (1 mg/kg and 6 mg/kg) on six sleep-waking phases was
      electroencephalographically (EEG) examined in young, middle-aged, and old male
      Wistar rats. Because 5-HT2 receptor binding sites decrease with aging, the
      question of whether ketanserin can produce any effect on sleep-wake in advanced
      age was addressed. Ketanserin enhanced deep slow wave sleep in the three age
      groups. However, in the old rats this effect was much less pronounced and did not
      depend on the dose. Only in the young and middle-aged animals, ketanserin reduced
      wakefulness in a dose-dependent manner. The suppression of paradoxical sleep with
      ketanserin did not depend on the age. The results suggest that the model of aging
      may be useful to study the functional role of 5-HT2 receptors in sleep-waking
      regulation.

PMID- 9639244
TI  - Age-related effect of ritanserin on the sleep-waking phases in rats.
AB  - The age-related effect of the specific 5-hydroxytryptamine-2A/2C (5-HT(2A/2C))
      antagonist ritanserin at two doses 0.63 mg/kg and 2.5 mg/kg) on six sleep-waking
      phases in young, middle-aged, and old male Wistar rats was
      electroencephalographically (EEG) examined. Only in the young and middle-aged
      rats, ritanserin enhanced slow wave sleep and reduced wakefulness in a dose
      dependent manner. Ritanserin suppressed paradoxical sleep, such that this effect
      did not depend on the age. Although the effect of ritanserin on slow wave sleep
      was significantly smaller in the old compared to the young and the middle-aged
      rats, ritanserin produced an apparent sleep-improving effect in the old age
      group.

PMID- 9639245
TI  - Dichotic memory: paradoxical effect of removing a left frontal gyrus: a case
      study.
AB  - A 27-year-old right-handed woman was operated with resection of an epileptogenic
      lesion, a nonmalignant tumor, in the left frontal lobe. The surrounding cortical
      and subcortical tissue in the tumor-containing gyrus was also resected. Care was
      taken during the operation not to interfere with motor or language related
      cortical areas. Pre- and postoperatively, she was tested with a dichotic memory
      test. In the preoperative test, she showed a marked Left Ear Advantage. In the
      corresponding tests on the second and fourth postoperative days and at follow-up,
      her performance had changed to a Right Ear Advantage. A possible explanation of
      this result is that neighboring cortical areas involved in hemispheric
      specialization for lateralized, verbal cognitive functions are suppressed by a
      focal epiletogeneic activity caused by the tumor. The subsequent removal of this
      influence allowed these cortical areas to function normally.

PMID- 9639246
TI  - The in vitro effect of substance P on the GnRH-induced LH release depends on the
      steroidal environment and is reverted by a NK1 receptor antagonist (RP 67580) in
      the cycling female rat.
AB  - A previously study reported that administration of substance P on the morning of
      the proestrous day induces an inhibition of afternoon gonadotropin preovulatory
      surges in the female rat. It has also been shown, with a non-peptide specific
      antagonist of the neurokinin 1 (NK1) receptor (RP 67580), that this effect is
      mediated by NK1 receptors. The present study used perifused anterior pituitaries
      from proestrous morning female rats and showed that the SP modulation of the GnRH
      induced LH release is markedly dependent on the steroidal environment. In the
      absence of steroids or in the presence of 17beta estradiol, or a combination of
      17beta estradiol and progesterone, SP inhibited the GnRH-induced LH release. In
      contrast, SP stimulated the GnRH-induced LH secretion in the presence of
      progesterone alone. However, the inhibitory or stimulatory effect of SP was
      antagonized by the specific NK1 receptor antagonist RP 67580.

PMID- 9639247
TI  - Cholecystokinin peptides and receptor binding in rat brain after DSP-4 treatment.
AB  - The neurotoxin DSP-4 has, in this laboratory, previously been shown to upregulate
      cholecystokinin (CCK) binding in the frontal cortex and the hippocampus in rats.
      The present study investigated the effect of DSP-4 on CCK peptide levels and CCK
      receptor binding in some rat brain areas. Sprague-Dawley rats were given single
      injections of DSP-4 (10 and 50 mg/kg) and examined after 1 week. Wistar rats were
      given an injection of DSP-4 (50 mg/kg) and evaluated 1 week and 4 months after
      treatment. No significant changes in CCK levels or in CCK binding were found. It
      has been found that stress produced by handling of the rats immediately before
      decapitation can result in an increase in cortical CCK receptor binding. This
      finding led to the speculation that the upregulation of CCK binding after DSP-4
      treatment which was reported earlier, reflects a stress-potentiating effect of
      DSP-4.

PMID- 9639248
TI  - A comparison of actions of neuropeptide Y (NPY) agonists and antagonists at NPY
      Y1 and Y2 receptors in anaesthetized rats.
AB  - The pancreatic polypeptide family includes three members, neuropeptide Y (NPY),
      peptide YY (PYY) and pancreatic polypeptide (PP), with sequence homology between
      members and species varying from approximately 50 to 80%. Some of these peptides
      were compared in the mammalian cardiovascular system for activity mediated by
      actions on pre- (Y2) and post-junctional (Y1) NPY receptors. NPY and PYY, with
      sequence homology of 67% have similar actions on Y1 and Y2 receptors. Rat
      pancreatic polypeptide (rPP) with sequence homology of approximately 50% is
      inactive at both. This study reports that the chimeric peptide, hPP1-11/NPY12-36
      and the truncated peptide NPY2-36 show similar activity to NPY mediated through
      both receptor types in vivo, while salmon PYY (sPYY), with 81% homology to NPY,
      has improved potency at both receptor subtypes. NPY3-36 has equal activity with
      NPY on actions mediated through Y2 receptors, but significantly reduced activity
      mediated through Y1 receptors. Two NPY antagonists were also examined: PYX2 was
      inactive in vivo and 1229U91 showed potent, long-lasting activity on Y1 receptor
      mediated effects.

PMID- 9639249
TI  - Measurement of cytokines in the cavernous sinus plasma from patients with
      Cushing's disease.
AB  - In order to know more about the in vivo secretion of various cytokines from the
      human pituitary, this study measured the concentrations of interleukin (IL)
      1alpha, IL-1beta, IL-2, IL-6, tumor necrosis factor-alpha and IL-1 receptor
      antagonist (ra) in both the peripheral blood and the cavernous sinus (CS) plasma
      from six patients with Cushing's disease before and after an intravenous bolus
      injection of human corticotropin-releasing hormone (CRH, 100 microg). As a
      routine procedure for the diagnosis of Cushing's disease, adrenocorticotropin
      (ACTH) levels were also determined in the same samples. In four of the six
      patients, unstimulated levels of IL-1ra in the CS ipsilateral to the ACTH
      secreting adenoma were higher than those in the peripheral blood, with a ratio of
      > or = 1.5:1, even though CRH was without effect on the cytokine's concentration
      in the CS. In contrast, no consistent data were obtained for any of the remaining
      five cytokines. These results demonstrate for the first time that the in vivo
      release of IL-1ra is detectable in at least some corticotroph adenomas, and also
      suggest a possible role of the cytokine in physiological and pathophysiological
      processes occurring in the human pituitary.

PMID- 9639250
TI  - Effect of melatonin on arginine vasopressin secretion stimulated by physical
      exercise or angiotensin II in normal men.
AB  - The present study was undertaken in order to establish the possible involvement
      of melatonin in the mechanisms underlying the arginine-vasopressin (AVP)
      responses to physical exercise and angiotensin II (ANG II). On two mornings at
      least 1 week apart, normal male subjects were tested with exercise on a bicycle
      ergometer (the workload was gradually increased at 3-min intervals until
      exhaustion and lasted about 15 min in all subjects) or ANG II (60-min infusion of
      ANG II (Asp 1, IIe 5 angiotensin II) dissolved in 5% glucose in successively
      increasing doses of 4, 8, 16 ng/kg/min; each dose for 20 min). Tests were carried
      out with the administration of either 6 mg melatonin or placebo. Melatonin
      treatment neither modified the basal concentrations of AVP nor changed the AVP
      response to ANG II. In contrast, plasma AVP levels rose 3.6 times during exercise
      in the absence of melatonin, but only 2.3 times in the presence of melatonin.
      These data indicate an involvement of melatonin in the mechanism underlying the
      AVP response to physical exercise, but not ANG II, in normal men.

PMID- 9639251
TI  - The C-terminal tetrapeptide of beta-endorphin (MPF) enhances lymphocyte
      proliferative responses.
AB  - Human MPF (Lys-Lys-Gly-Glu) stimulates the proliferative response of human
      lymphocytes to the T-cell mitogen concanavalin A by 121-751% in the concentration
      range 10(-11)-10(-4) M; the peak effect is at 10(-8) M, lower or higher
      concentrations eliciting reduced responses, i.e. the dose-response curve is bell
      shaped. Species specificity is high. Human MPF similarly stimulates rat
      lymphocytes, but the peak effect is seen at a 100-fold higher dose (10(-6) M).
      Rat MPF (Lys-Lys-Gly-Gln) has a peak effect at 10(-6) M with human lymphocytes,
      but the peak effect with rat lymphocytes is at a 1000-fold lower dose (10(-9) M).
      Truncated forms of the MPFs (Gly-Glu, Gly-Gln, Gly, Glu, Gln) and opioid peptides
      (beta-endorphin, [Leu] and [Met]enkephalin) show insignificant or only weak
      stimulatory or inhibitory effects. These results suggest that MPF acts via
      specific non-opioid receptors located on lymphocytes and that endogenously
      released MPF may have an important role in the functioning of the immune system.

PMID- 9639252
TI  - Penetration of dynorphin 1-13 across the blood-brain barrier.
AB  - Previous studies have demonstrated neuroprotective effects of the opioid peptide
      dynorphin (dyn) 1-13 in focal cerebral ischemia. The passage of dyn 1-13 across
      the blood-brain barrier (BBB) was studied by a modification of the Oldendorf
      technique in the normal rat and cat, as well as in a feline model of
      experimentally induced focal cerebral ischemia. In the rat, dyn 1-13 penetration
      of the BBB could not be detected by this technique, even in the presence of
      peptidase inhibitors. In contrast, dyn 1-13 did cross the BBB into the normal cat
      hippocampus, cortex and cerebellum. The passage of dyn 1-13 across the BBB was
      greater in cats with experimentally induced focal cerebral ischemia. Some of the
      tritium-labeled material which crossed the BBB was confirmed by high performance
      liquid chromatography to be dyn 1-13. These studies support the hypothesis that
      the therapeutic effects observed after the peripheral administration of dyn 1-13
      to cats with focal cerebral ischemia can be produced by a central mechanism of
      action.

PMID- 9639253
TI  - Diabetic rats are unresponsive to the penile erection-inducing effect of
      intracerebroventriculary injected adrenocorticotropin.
AB  - The penile erection-inducing effect of intracerebroventricularly (i.c.v.)
      injected adrenocorticotropin-(1-24) [ACTH-(1-24)] (4 or 10 microg/animal) was
      almost completely absent in diabetic rats, either 8 days or 2 months after
      streptozotocin administration. The other behavioral symptoms (stretching,
      yawning, excessive grooming) were unevenly affected: stretching was significantly
      reduced either in early or in long-standing diabetes; yawning was practically
      absent in early diabetes and significantly reduced at the highest dose of ACTH-(1
      24) in long-standing diabetes; grooming was reduced only at the highest dose of
      ACTH-(1-24), both in early and in long-standing diabetes. The fact that ACTH
      induced penile erections (a centrally mediated effect) are practically absent
      even a few days after streptozotocin injection suggests that diabetes mellitus
      induced penile dysfunction occurs, at least in part, through central mechanisms,
      and is not solely the consequence of peripheral nerve and vascular lesions.

PMID- 9639254
TI  - The cholecystokinin-B receptor antagonist L-740,093 produces an insurmountable
      antagonism of CCK-4 stimulated functional response in cells expressing the human
      CCK-B receptor.
AB  - A stable cell line expressing the human cholecystokinin-B receptor gene (hCCK
      B.CHO) has been employed in an evaluation of the recently developed CCK-B
      receptor antagonist L-740,093. L-740,093 exhibited high affinity (IC50 0.49 nM)
      and selectivity (<50% displacement at CCK-A sites at 1 microM) for the human CCK
      B receptor subtype as estimated from [125I]-CCK-8S displacement studies with
      membranes prepared from hCCK-B.CHO cells. The elevation of intracellular free
      Ca2+ in hCCK-B.CHO cells in response to stimulation with CCK-4 was used to
      evaluate the antagonist activity of L-740,093 in vitro. L-740,093 potently (IC50
      5.4 nM) antagonized the 30 nM CCK-4-stimulated Ca2+ mobilization in hCCK-B.CHO
      cells. Further studies were performed to investigate the nature of the antagonist
      activity of L-740,093. When tested at 10 nM L-740,093 produced a modest rightward
      shift in the CCK-4 dose response curve, an effect which was accompanied by a
      small reduction (13%) in the maximum response to CCK-4. In the presence of 30 nM
      L-740,093 the maximum functional response to CCK-4 was further reduced by 45%
      indicating that L-740,093 behaves as an insurmountable antagonist of the human
      CCK-B receptor subtype.

PMID- 9639255
TI  - Extracellular dopamine in the anterior nucleus accumbens is distinctly affected
      by ventral tegmental area administration of cholecystokinin and apomorphine: data
      from in vivo voltammetry.
AB  - The interaction of cholecystokinin (CCK) and dopamine (DA) in the mesolimbic
      system was investigated. The study focused on DAergic cells not containing
      colocalized CCK projecting from the ventral tegmental area (VTA) to the anterior
      nucleus accumbens (NA). Differential pulse voltammetry in pargyline pretreated
      and anesthetized rats was used to measure extracellular DA in the anterior NA
      following microinjection of apomorphine either alone or in combination with CCK
      8s into the VTA. In agreement with an earlier study there was a dose-dependent
      increase in the DA signal in the anterior NA after microinjection of CCK-8s into
      the VTA. Apomorphine microinjected into the VTA produced a biphasic effect on
      extracellular DA in the anterior NA with an increase from basal levels of
      approximately 50% by 1 ng, whereas 10 ng was ineffective and 100 ng apomorphine
      caused a slight decrease in the DA signal. Apomorphine (1 ng) microinjected
      together with 1 ng CCK-8s produced an increase in the DA signal to approximately
      180% of the baseline value, whereas the combination of 1 ng apomorphine and 100
      ng CCK-8s was ineffective. When 100 ng apomorphine were microinjected in
      combination with either 1 ng or 100 ng CCK-8s, the DA signal in the anterior NA
      was unchanged. These results suggest that low doses of apomorphine injected into
      the VTA synergistically influence the effects of CCK-8s on extracellular DA in
      the anterior NA, whereas higher doses of apomorphine suppress the effect of CCK
      8s on DAergic cells projecting to the anterior NA.

PMID- 9639256
TI  - Expression and protective effects of urocortin in cardiac myocytes.
AB  - Reverse transcription PCR showed that mRNA encoding the CRH-like molecule,
      urocortin, is expressed in a rat cardiac myocyte cell line and in primary
      cultures of cardiac myocytes. Identity of the amplified with the published
      sequence was established by restriction mapping and direct sequencing. Expression
      of urocortin mRNA was increased 12-18 h after thermal injury. Urocortin peptide
      protected cardiac myocytes from cell death induced by hypoxia. The data suggest
      that urocortin is an endogenous cardiac myocyte peptide which modulates the
      cellular response to stress.

PMID- 9639257
TI  - Opioids modulate the calcitonin gene-related peptide8-37-mediated hindpaw
      withdrawal latency increase in thermally injured rats.
AB  - The present study was performed to explore the modulatory potential of different
      endogenous opioid systems on transmission of presumed nociceptive information at
      the spinal cord level in thermally injured rats. Thermal injury was performed by
      dipping the left paw into water 60 degrees C for 20 s. This induced a significant
      bilateral decrease in hindpaw withdrawal latency HWL to pressure. Intrathecal
      administration of 10 nmol of CGRP8-37 induced a significant bilateral increase in
      HWL in the thermally injured group and in the intact controls. The effect of
      different opioid receptor antagonists on the increased latency to withdrawal
      response induced by intrathecal injection of 10 nmol of CGRP8-37 was explored in
      the thermally injured rats. The effect was reversed by intrathecal injection of
      40 and 80 nmol of: b-funaltrexamine (mu opioid receptor antagonist) and
      naltrindole (delta opioid receptor antagonist), but not by norbinaltorphimine
      (kappa opioid receptor antagonist). The results of the present study show that
      intrathecal CGRP8-37 increases hindpaw withdrawal latency in thermally injured
      rats, an effect reduced by a mu as well as by a delta opioid receptor antagonist.

PMID- 9639258
TI  - Increased concentrations of calcitonin gene-related peptide-like immunoreactivity
      in rat brain and peripheral tissue after ischaemia: correlation to flap survival.
AB  - The effects of experimentally induced ischaemia after free-flap surgery on
      concentrations of neuropeptide Y (NPY), neurokinin A (NKA), substance P (SP) and
      calcitonin gene-related peptide (CGRP)-like immunoreactivity (-LI) were studied
      in flap tissue and in different regions of the rat brain (striatum, hippocampus,
      pituitary, hypothalamus, frontal and occipital cortex). Ten days after the
      operation, CGRP-LI and NKA-LI were decreased in the ischaemic tissue but
      increased in the surrounding tissue. In the brain, CGRP-LI was increased in five
      of six regions analysed, with the exception of the striatum. SP-LI and NKA-LI
      were increased in the pituitary and hippocampus, but decreased in other brain
      regions. Changes of CGRP-LI in the brain correlated positively with the CGRP-LI
      concentrations in the surrounding flap tissue and the CGRP-LI concentrations in
      the ischaemic flap tissue with the extent of flap survival. The results of the
      present study suggest that higher concentrations of CGRP-LI are related to tissue
      survival and that endogenous CGRP has a regulatory effect in ischaemia.

PMID- 9639259
TI  - Protein kinase C is involved in cholecystokinin octapeptide-induced proliferative
      action in rat glioma C6 cells.
AB  - Chotecystoknin octapeptide (CCK-8) has been shown to stimulate DNA synthesis in
      rat glioma C6 cells by activation of CCKB type receptors. However, the signalling
      pathways contributing to this proliferative action in C6 cells have not been
      investigated thus far. This study demonstrated that stimulation of rat glioma C6
      cells with CCK-8S resulted in activation of protein kinase C isozymes betaI,
      betaII, gamma and zeta. The participation of protein kinase C in the CCK-8S
      induced effect on C6 cell growth was demonstrated by measurement of [3H]thymidine
      incorporation and estimation of cell number. The data indicate that CCK-8S
      stimulates growth in rat glioma C6 cells by a protein kinase C-dependent
      mechanism.

PMID- 9639260
TI  - Identification of the spinal degradation products and inhibition of adenylate
      cyclase by recombinant rat galanin message-associated peptide.
AB  - In rat preprogalanin, galanin is C-terminally flanked by a 60 amino acid long
      peptide: galanin message-associated peptide (GMAP). GMAP sequences in different
      species show high degree of homology, suggesting a biological role. However, the
      study of the physiological and pharmacological actions of this peptide have been
      hampered by lack of availability of this large peptide, its fragments and well
      characterized antibodies to GMAP. This study report the production of GMAP in
      Escherichia coli and the use of the recombinant peptide to define its degradation
      products in the spinal cord. The GMAP fragments formed upon incubation of GMAP
      with membranes of lumbar spinal cord were identified by sequencing and were also
      produced by solid phase synthesis for studies on second messenger systems.
      Furthermore, the study demonstrates that GMAP inhibits forskolin stimulated
      adenylate cyclase activity in a concentration dependent manner, while GMAP and
      its synthetic fragments did not affect cGMP level.

PMID- 9639261
TI  - Reduction of sensory and metabotropic glutamate receptor responses in the
      thalamus by the novel metabotropic glutamate receptor-1-selective antagonist S-2
      methyl-4-carboxy-phenylglycine.
AB  - Previous work has shown that responses of thalamic neurons in vivo to the
      metabotropic glutamate receptor agonists 1S,3R-aminocyclopentane-1,3
      dicarboxylate and S-3,5-dihydroxyphenylglycine can be reduced by a variety of
      phenylglycine antagonists. Responses of thalamic neurons to noxious thermal
      somatosensory stimuli were reduced in parallel by these antagonists, indicating
      that these responses are mediated by Group I metabotropic glutamate receptors
      (i.e. metabotropic glutamate receptor-1 and/or metabotropic glutamate receptor
      5), which are known to be linked to phosphoinositol phosphate hydrolysis. The
      recent development of S-2-methyl-4-carboxyphenylglycine as an antagonist which is
      highly selective for metabotropic glutamate receptor-1 compared to metabotropic
      glutamate receptor-5 on human receptors expressed in AV-12 cells, now offers the
      possibility of discriminating between these two receptor subtypes in order to
      distinguish which is involved in thalamic responses. We have made recordings from
      single somatosensory neurons in the thalamus of the rat, and find that S-2-methyl
      4-carboxy-phenylglycine is able to reduce responses of neurons to 1S,3R
      aminocyclopentane-1,3-dicarboxylate, S-3,5-dihydroxyphenylglycine, and noxious
      stimuli without significant effect on responses to either N-methyl-D-aspartate or
      (+/-)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate. These results suggest
      that excitatory responses of thalamic neurons to 1S,3R-aminocyclopentane-1,3
      dicarboxylate and S-3,5-dihydroxyphenylglycine may be mediated by metabotropic
      glutamate receptor-1. Furthermore, the reduction of nociceptive responses by S-2
      methyl-4-carboxy-phenylglycine indicates that metabotropic glutamate receptor-1
      is involved in thalamic nociceptive processing and that such antagonists may have
      analgesic properties.

PMID- 9639262
TI  - Nociceptive stimulus induces release of endogenous beta-endorphin in the rat
      brain.
AB  - The hypothesis that the naturally occurring analgesic peptide, beta-endorphin, is
      released in the brain in response to pain had never been directly validated. In
      this study, we applied a brain microdialysis method for monitoring beta-endorphin
      release in vivo, to test this hypothesis in the brains of conscious, freely
      moving rats. Herein we first show that endogenous beta-endorphin can be measured
      in vivo in the brain under physiological conditions. Upon induction of a
      nociceptive stimulus by injection of formalin into the hind-paws of rats, the
      extracellular levels of beta-endorphin in their arcuate nucleus increased by 88%,
      corresponding to their nociceptive response. This direct evidence for the release
      of endogenous beta-endorphin in the brain in response to nociceptive stimulus
      indicates a possible mechanism for organisms to cope with pain.

PMID- 9639263
TI  - Putative gap junctional communication between axon and regenerating Schwann cells
      during mammalian peripheral nerve regeneration.
AB  - Gap junctions are intercellular channels which mediate the traffic of ions and a
      variety of molecular messengers between contiguous cells. Here, we report on the
      possibility that atypical gap junctions develop between heterologous tissues,
      such as regenerating nerve axons and Schwann cells, during peripheral nerve
      regeneration in adult rats. After a complete transection and subsequent
      regeneration in the rat sciatic nerve distal segment, a small scale gap junction
      like structure was observed between the regenerating axons and adjoining Schwann
      cells. Immunoelectron microscopy showed that one of the gap junctional proteins,
      connexin32, was located at a small region of contact between the axon and Schwann
      cells. Biocytin, a small molecular weight dye, was transported from regenerating
      axons into adjoining Schwann cells. The present findings suggest that
      regenerating axons communicate directly with adjacent Schwann cells through small
      gap junctions, which may play a role in the mechanism of regeneration following
      nerve transection.

PMID- 9639264
TI  - Dopamine facilitates long-term depression of glutamatergic transmission in rat
      prefrontal cortex.
AB  - Using sharp-electrode intracellular recordings, we studied the dopaminergic
      facilitation of synaptic plasticity in layer I-II afferents--layer V neuron
      glutamatergic synapses in rat prefrontal cortex in vitro. Tetanic stimulation
      (100 pulses at 50 Hz, four times at 0.1 Hz) to layer I-II afferents induced N
      methyl-D-aspartate receptor-independent long-term depression (>40 min) of the
      glutamatergic synapses when the stimulation was coupled with a bath-application
      of dopamine. Tetanic stimulation alone did not induce lasting synaptic changes.
      Dopamine application alone transiently depressed synaptic responses, which fully
      recovered within 30 min. Pharmacological analyses with antagonists suggested that
      dopamine action on either D1-like or D2-like receptors can facilitate the
      induction of long-term depression. However, results with agonists were not fully
      consistent with the antagonist results: while a D2 agonist mimicked the
      facilitatory dopamine effect, D1 agonists failed to mimic the effect. We also
      analysed the synaptic responses during tetanus and found that dopamine prolongs
      membrane depolarization during high-frequency inputs. Postsynaptic membrane
      depolarization is indeed critical for long-term depression induction in the
      presence of dopamine, since postsynaptic hyperpolarization during tetanus blocked
      the dopaminergic facilitation of long-term depression induction. Postsynaptic
      injection of the Ca2+ chelator bis-(o-aminophenoxy)-N,N,N',N'-tetra-acetic acid
      (100 mM in the electrode) also blocked long-term depression induction. Our
      results show that dopamine lowers the threshold for long-term depression
      induction in rat prefrontal glutamatergic transmission. A possible underlying
      mechanism of this dopaminergic facilitation is the enhancement of postsynaptic
      depolarization during tetanus by dopamine, which may increase the amount of Ca2+
      entry from voltage-gated channels to the level sufficient for plasticity
      induction.

PMID- 9639265
TI  - Neurochemical features and synaptic connections of large physiologically
      identified GABAergic cells in the rat frontal cortex.
AB  - Physiological and morphological properties of large non-pyramidal cells
      immunoreactive for cholecystokinin, parvalbumin or somatostatin were investigated
      in vitro in the frontal cortex of 18-22-day-old rats. These three peptides were
      expressed in separate populations including large cells. Cholecystokinin cells
      and parvalbumin cells made boutons apposed to other cell bodies, but differed in
      their firing patterns in response to depolarizing current pulses. Parvalbumin
      cells belonged to fast-spiking cells. Parvalbumin fast-spiking cells also
      included chandelier cells. In contrast, cholecystokinin cells were found to be
      regular-spiking non-pyramidal cells or burst-spiking non-pyramidal cells with
      bursting activity from hyperpolarized potentials (two or more spikes on slow
      depolarizing humps). Large somatostatin cells belonged to the regular-spiking non
      pyramidal category and featured wide or ascending axonal arbors (wide arbor cells
      and Martinotti cells) which did not seem to be apposed to the somata so
      frequently as large cholecystokinin and parvalbumin cells. For electron
      microscopic observations, another population of eight immunohistochemically
      uncharacterized non-pyramidal cells were selected: (i) five fast spiking cells
      including one chandelier cell which are supposed to contain parvalbumin, and (ii)
      three large regular-spiking non-pyramidal cells with terminals apposed to somata,
      which are not considered to include somatostatin cells, but some of which may
      belong to cholecystokinin cells. The fast-spiking cells other than a chandelier
      cell and the large regular-spiking non-pyramidal cells made GABA-positive
      synapses on somata (4% and 12% of the synapses in two small to medium fast
      spiking cells, 22% and 35% of the synapses in two large fast-spiking cells, and
      10%, 18% and 37% of the synapses in three large regular-spiking non-pyramidal
      cells). A few terminals of the fast-spiking and regular-spiking non-pyramidal
      cells innervated GABAergic cells. About 30% of the fast-spiking cell terminals
      innervated spines, but few of the regular-spiking non-pyramidal cell terminals
      did. A fast-spiking chandelier cell made GABA-positive synapses on GABA-negative
      axon initial segments. These results suggest that large GABAergic cells are
      heterogeneous in neuroactive substances, firing patterns and synaptic
      connections, and that cortical cells receive heterogeneous GABAergic somatic
      inputs.

PMID- 9639266
TI  - Effects of lesions in the mesial frontal cortex on bimanual co-ordination in
      monkeys.
AB  - The hypothesis was tested that the mesial frontal cortex, including the
      supplementary motor area, is engaged in bimanual co-ordination. Three monkeys,
      trained in a well-co-ordinated bimanual pull-and-grasp task, were subjected to
      unilateral or bilateral lesions of the mesial frontal cortex. With unilateral
      lesions, the deficit consisted in a delay in movement initiation of the
      contralateral arm. With a bilateral lesion, the deficit was more pronounced with
      marked bilateral delays in movement onset and slowing in reaching. However, in
      the three monkeys bimanual co-ordination at the moment of goal achievement
      remained intact with an excellent temporal co-variation of the two limbs. In the
      two unilateral cases, an adaptive strategy developed after a few sessions, either
      by catching up during reaching with the limb contralateral to the lesion (monkey
      M1) or by delaying movement initiation of the limb ipsilateral to the lesion
      (monkey M2). This outcome is discussed in terms of Lashley's principle of motor
      equivalence, i.e. invariant goal achievement with variable means. Bilateral
      lesions led to a transient and near-total impairment in movement self-initiation
      when all external cues were absent. It is concluded that in monkeys the mesial
      frontal cortex does not play a crucial role in bimanual co-ordination but rather
      in movement initiation, especially when sensory cues are absent.

PMID- 9639267
TI  - Two visual areas located in the middle suprasylvian gyrus (cytoarchitectonic
      field 7) of the cat's cortex.
AB  - Neuronal properties and topographic organization of the middle suprasylvian gyrus
      (cortical cytoarchitectonic field 7) were studied in three behaving cats with
      painlessly fixed heads. Two main neuronal types were found within this field.
      Type 1 neurons occupied the lateral part of the field and bordered representation
      of directionally selective neurons of the lateral suprasylvian visual area by
      vertical retinal meridian. Type 1 neurons had elongated and radially oriented
      receptive fields located in the lower part of contralateral visual field. Type 1
      neurons preferred stimuli moving out or to the centre of gaze at a low or
      moderate speed, and many of them were depth selective. The responses were
      enhanced by attention, oriented to the presented stimulus. Medial part of the
      field 7 along the border with the area V3 was occupied by neurons with not
      elongated receptive fields (type 2). These neurons preferred moderate and high
      speeds of motion, and gratings of proper spatial frequency and orientation were
      effective stimuli for them. Border between representations of type 2 and type 1
      neurons coincided with projection of horizontal retinal meridian. At the rostral
      and caudal borders of the field 7 abrupt changes of neuronal properties took
      place. Neurons which abutted field 7 anteriorly and posteriorly resembled
      hypercomplex cells and their small receptive fields were located in the central
      part of the visual field. Topographical considerations and receptive field
      properties allowed us to conclude that the medial part of the field 7 (included
      type 2 neurons) is functionally equivalent to the area V4 in the cortex of
      primates, while the lateral part (type 1 neurons) may correspond to the area V4T.

PMID- 9639268
TI  - Differential expression of rat and human type I metabotropic glutamate receptor
      splice variant messenger RNAs.
AB  - The type I metabotropic glutamate receptor (mGlu1) messenger RNA and protein are
      known to be widely expressed in rat brain, but knowledge of the regional
      expression of splice variants other than mGlu1a is limited. Probes were designed
      for in situ hybridization that specifically recognize each of the carboxy
      terminal splice variants mGlu1a, -1b, -1c and -1d. The novel rat mGlu1d sequence
      was obtained by polymerase chain reaction and the predicted protein is highly
      homologous to the human sequence but contains both conservative and radical
      substitutions and is slightly longer (912 vs 908 amino acids). Each rat mGlu1
      splice variant messenger RNA was found in a unique expression pattern. The
      messenger RNA encoding mGlu1a was abundant in cerebellar Purkinje cells and in
      mitral and tufted cells of the olfactory bulb. Strong expression was also
      detected in hippocampal interneurons, and neurons of the thalamus and substantia
      nigra, while moderate expression was found in colliculi and cerebellar granule
      cells. The mGlu1b messenger RNA was strongly expressed in Purkinje cells,
      hippocampal pyramidal neurons, dentate gyrus granule cells and lateral septum,
      and moderately expressed in striatal, superficial cortical and cerebellar granule
      neurons. The mGlu1d messenger RNA was expressed in all regions where mGlu1a and 
      1b were detected; abundant in Purkinje cells, mitral and tufted cells, and
      hippocampal principal neurons and interneurons, strong in thalamus and substantia
      nigra, and moderate in lateral septum, cortex, striatum and colliculi. Human
      mGlu1 splice variant expression in the cerebellum matched that found for the rat.
      No specific signal was found with a probe capable of hybridizing to the rat
      mGlu1c splice junction, although another probe designed against a more 3'
      sequence of mGlu1c gave strong signals in the cerebellum and hippocampus, and
      moderate signals in thalamus and colliculi. It is concluded that mGlu1d messenger
      RNA is widely expressed, that mGlu1a and -1b messenger RNAs are expressed in
      almost complementary patterns and that formation of the mGlu1c splice junction is
      a rare event.

PMID- 9639269
TI  - Neuroprotective activity of N-acetylaspartylglutamate in cultured cortical cells.
AB  - The endogenous dipeptide, alpha-N-acetylaspartylglutamate behaves as a partial
      agonist of N-methyl-D-aspartate receptors, but can also activate metabotropic
      glutamate receptors, with a high degree of selectivity for the metabotropic
      glutamate receptor 3 subtype. Knowing that agonists of group-II metabotropic
      glutamate receptors (i.e. of mGlu2 and -3 receptors) are neuroprotective, we have
      examined the neuroprotective activity of alpha-N-acetylaspartylglutamate in mixed
      cultures of mouse cortical cells exposed to a toxic pulse with N-methyl-D
      aspartate. Alpha-N-acetylaspartylglutamate co-applied with N-methyl-D-aspartate
      was neuroprotective, but its action was insensitive to the selective group-II
      metabotropic glutamate receptor antagonist, ethylglutamate. Protection was
      instead antagonized by ethylglutamate when alpha-N-acetylaspartylglutamate was
      applied to the cultures immediately after the N-methyl-D-aspartate pulse, a
      condition in which there was no direct competition between alpha-N
      acetylaspartylglutamate and N-methyl-D-aspartate at the level of N-methyl-D
      aspartate receptors. alpha-N-acetylaspartylglutamate was highly neuroprotective
      when transiently applied to pure cultures of cortical astrocytes and the
      conditioned medium, collected 20 h later, was transferred to sister mixed
      cultures challenged with N-methyl-D-aspartate. This particular form of
      neuroprotection was attenuated or abolished when astrocytes where exposed to
      alpha-N-acetylaspartylglutamate in the presence of the group-II metabotropic
      glutamate receptor antagonists ethylglutamate or (2S, 1'S,2'S,3'R)-2-(2'-carboxy
      3'-phenylcyclopropyl)glycine, but not in the presence of the N-methyl-D-aspartate
      receptor antagonist, D-2-amino-5-phosphonopentanoate. These results indicate that
      alpha-N-acetylaspartylglutamate induces neuroprotective effects in culture, which
      are mediated, at least in part, by the activation of glial metabotropic glutamate
      receptor 3 receptors.

PMID- 9639270
TI  - Expression of HNK-1 carbohydrate and its binding protein, SBP-1, in apposing cell
      surfaces in cerebral cortex and cerebellum.
AB  - Sulfoglucuronyl carbohydrate is the terminal moiety of neolacto-oligosaccharides,
      expressed on several glycoproteins of the immunoglobulin superfamily involved in
      cell-cell recognition and on two glycolipids. Sulfoglucuronyl carbohydrate is
      temporally and spatially regulated in the developing nervous system. It appears
      to be involved in neural cell recognition and in cell adhesion processes through
      its interaction with specific proteins on cell surfaces. Previously we have
      characterized a specific sulfoglucuronyl carbohydrate-binding protein in rat
      brain. Sulfoglucuronyl carbohydrate binding protein-1 is structurally similar to
      a 30,000 mol. wt adhesive and neurite outgrowth promoting protein amphoterin
      [Rauvala and Pihlaskari (1987) J. biol. Chem. 262, p. 16,625]. The pattern of
      expression of sulfoglucuronyl carbohydrate binding protein-1 in developing rat
      nervous system was studied to understand the significance of its interaction with
      sulfoglucuronyl carbohydrate-bearing molecules. Biochemical analyses showed that
      the expression of sulfoglucuronyl carbohydrate binding protein-1 was
      developmentally regulated similarly to sulfoglucuronyl carbohydrate.
      Immunocytochemical localization of sulfoglucuronyl carbohydrate binding protein-1
      and sulfoglucuronyl carbohydrate was performed by bright-field and fluorescent
      confocal laser scanning microscopy. In postnatal day 7 rat cerebellum,
      sulfoglucuronyl carbohydrate binding protein-1 was primarily associated with
      neurons of the external and internal granule cell layers. The sulfoglucuronyl
      carbohydrate binding protein-1 immunoreactivity was absent in Purkinje cell
      bodies and their dendrites in the molecular layer, as well as in Bergmann glial
      fibres and in white matter. In contrast, sulfoglucuronyl carbohydrate (reactive
      with HNK-1 antibody) was localized in processes surrounding granule neurons in
      the internal granule cell layer. Sulfoglucuronyl carbohydrate was also expressed
      in Purkinje neurons and their dendrites in the molecular layer and their axonal
      processes in the white matter. To a lesser extent Bergmann glial fibres were also
      positive for sulfoglucuronyl carbohydrate. In the cerebral cortex, at embryonic
      day 21, sulfoglucuronyl carbohydrate binding protein-1 was mainly observed in
      immature neurons of the cortical plate and subplate and dividing cells near the
      ventricular zone. Whereas, sulfoglucuronyl carbohydrate was strongly expressed in
      the fibres of the subplate and marginal zone. Sulfoglucuronyl carbohydrate was
      also found in the processes surrounding the sulfoglucuronyl carbohydrate binding
      protein-1-expressing neuronal cell bodies in the cortical plate and in
      ventricular zone. The specific localization of sulfoglucuronyl carbohydrate
      binding protein- in cerebellar granule neurons and neurons of the cerebral cortex
      was also confirmed by immunocytochemistry of the dissociated tissue cell
      cultures. The complementary localization of sulfoglucuronyl carbohydrate and
      sulfoglucuronyl carbohydrate binding protein-1, both in cerebral cortex and
      cerebellum, in apposing cellular structures indicate possible interaction between
      the two and signalling during the process of cell migration and arrest of
      migration.

PMID- 9639271
TI  - Cerebellar circuitry is activated during convulsive episodes in the tottering
      (tg/tg) mutant mouse.
AB  - Tottering (tg) is an autosomal recessive mutation of the calcium channel alpha1A
      subunit in the mouse that results in epileptic spike and wave discharges, mild
      ataxia and paroxysmal episodes of involuntary spasms of the limbs, trunk and
      face. These convulsions have been especially difficult to characterize because of
      their unpredictable occurrence and lack of electroencephalographic correlates.
      However, it is, in fact, possible to induce these convulsions, making this facet
      of the tottering phenotype amenable to controlled experimentation for the first
      time. Here, the neuroanatomical basis of the convulsions in tottering mice has
      been identified using in situ hybridization for c-fos messenger RNA to chart
      abnormal neuronal activity. Convulsion-induced c-fos messenger RNA expression was
      most prominent in the cerebellum of convulsing tottering mice. Additionally,
      cerebral cortex and principal cerebellar relay nuclei were also activated during
      a convulsion. The c-fos activation in the cerebellum temporally preceded
      expression in cerebral cortex, suggesting that cerebral cortex is not driving the
      expression of convulsions. These results suggest that the cerebellum, a region
      not classically associated with paroxysmal events, is important in the generation
      and/or maintenance of the intermittent convulsions in tottering mutant mice.

PMID- 9639272
TI  - A single pre-training glucose injection induces memory facilitation in rodents
      performing various tasks: contribution of acidic fibroblast growth factor.
AB  - Effects of a pre-training intraperitoneal glucose injection on learning and
      memory were tested using two tasks: passive avoidance and Morris water maze. In
      the former task, mice that had received glucose 2 h prior (but not 1, 3, or 5 h
      prior) to a trial that combined acquisition with passive avoidance of foot shock
      showed a significantly increased retention latency when tested 24 h later. Thus,
      this effect was time-dependent, and it was also found to be dose-dependent by
      further experiment. In contrast, 2-deoxy-D-glucose and fructose had no such
      effect. In the Morris water maze task, glucose injection 2 or 3 h before a block
      of trials enhanced the spatial memory performance of mice. These glucose-induced
      memory-facilitation effects were abolished by an intracerebroventricular
      injection of anti-acidic fibroblast growth factor antibody 30 min before the
      glucose injection, suggesting a critical role for endogenous acidic fibroblast
      growth factor in this facilitatory effect. Furthermore, continuous
      intracerebroventricular infusion of acidic fibroblast growth factor in rats
      significantly increased retention latency (when tested repeatedly on successive
      days using a passive avoidance task). Our earlier studies demonstrated that brain
      acidic fibroblast growth factor is produced in the ependymal cells of the
      cerebroventricular system, and is released into the cerebrospinal fluid following
      either a meal or a (intraperitoneal or intracerebroventricular) glucose
      injection. This released acidic fibroblast growth factor also diffuses into the
      brain parenchyma, and is taken up by neurons in the hippocampus, hypothalamus,
      and elsewhere in the brain some 2 h after the meal or glucose injection. These
      and the present findings indicate (i) that pre-training glucose injection
      improves memory performance, and (ii) that acidic fibroblast growth factor,
      especially by its action within the hippocampus, is involved in this enhancement
      process.

PMID- 9639273
TI  - Corticotropin-releasing hormone receptor (type I) antisense targeting reduces
      anxiety.
AB  - Two brain-derived corticotropin-releasing hormone receptors have been cloned,
      termed corticotropin-releasing hormone receptors type I and type 2. Antisense
      oligodeoxynucleotides targeted to the cloned rat and mouse corticotropin
      releasing hormone receptors type I messenger RNA reduced the binding of the
      natural ligand of the corticotropin-releasing hormone receptors type I and also
      the release of adenocorticotrophic hormone in primary rat anterior pituitary
      cells and in clonal mouse pituitary cells (AtT-20) by up to 60% in an application
      time-dependent manner. Studies on intracellular uptake of fluorescence-labelled
      oligodeoxynucleotides indicated a cytoplasmic accumulation starting within two to
      four hours after application of oligodeoxynucleotides in vitro. In vivo,
      antisense oligodeoxynucleotides infused intra-cerebroventricularly reduced
      binding of radiolabelled corticotropin-releasing hormone receptors in central
      sites of the rat brain. Anxiety induced by i.c.v. administration of corticotropin
      releasing hormone was attenuated by corticotropin-releasing hormone receptors
      type I antisense treatment as determined in the elevated plus maze and in the
      novel open field test. The corticotropin-releasing hormone-induced behavioural
      changes were absent in corticotropin-releasing hormone receptors type I antisense
      pretreated animals. These results show that the selected antisense probes used
      were able to suppress corticotropin-releasing hormone receptors type I function
      in vitro as well as in vivo and suggest that the development of drugs blocking
      this specific receptor might lead to a novel class of anxiolytics.

PMID- 9639274
TI  - The role of alpha-2 receptors in the medial preoptic area in the regulation of
      sleep-wakefulness and body temperature.
AB  - The study was conducted on 48 free-moving male rats to find out the role of the
      medial preoptic alpha2 receptors in the regulation of sleep and body temperature.
      Recording electrodes for assessment of sleep-wakefulness, and injector cannulae
      for injection of drugs in the medial preoptic area were chronically fixed on the
      skulls of the animals. The noradrenergic fibres projecting to the medial preoptic
      area were destroyed in 24 rats by administration of 6-hydroxydopamine at the
      ventral noradrenergic bundle. Though arousal was produced in normal rats by the
      injection of the alpha2 adrenergic agonist, clonidine, at the medial preoptic
      area, it induced sedation in rats with noradrenergic fibre lesion. Clonidine did
      not alter the rectal temperature in normal rats but it induced hypothermia in
      lesioned rats. Injection of alpha2 antagonist, yohimbine, at the medial preoptic
      area induced sleep in rats with intact noradrenergic fibres. However, the sleep
      inducing effect of this drug was very much attenuated in the lesioned animals.
      There was no significant change in body temperature, in both these groups of
      animals, after yohimbine administration. The study indicates the role of
      presynaptic alpha2 adrenergic receptors in arousal response and indirectly
      supports the contention that the alpha1 postsynaptic receptors at the medial
      preoptic area are involved in hypnogenesis. It also suggests that the thermal
      changes induced by adrenergic system are mediated through alpha1 postsynaptic
      receptors. But the thermal changes do not contribute towards the induced
      alterations in sleep-wakefulness. It is proposed that there should be separate
      sets of noradrenergic terminals for regulation of sleep and body temperature.

PMID- 9639275
TI  - Galanin stimulates the N-methyl-D-aspartate receptor/nitric oxide/cyclic GMP
      pathway in vivo in the rat ventral hippocampus.
AB  - We investigated whether the neuropeptide galanin affects the nitric oxide
      synthase/cyclic GMP pathway in rat hippocampus by measuring in vivo the
      extracellular cyclic GMP levels during microdialysis. Galanin (2.5 and 3.5 nmol;
      i.c.v.) dose-dependently raised the extracellular levels of cyclic GMP in the
      ventral but not the dorsal hippocampus. The effect of 3.5 nmol galanin was
      blocked by local application of tetrodotoxin and inhibited by the high-affinity
      galanin antagonist M40 (galanin-[1-12]-Pro3-[Ala-Leu]2-Ala amide). The non
      competitive N-methyl-D-aspartate receptor antagonist dizocilpine maleate (30
      microM infused into the ventral hippocampus or 0.2 mg/kg, i.p.) and the
      competitive one, 3-([R]-carboxypiperazin-4-yl)-propyl-phosphonic acid (50 microM
      infused), but not local perfusion of the AMPA antagonist 6-nitro-7
      sulphamoylbenzo(f)quinoxaline-2,3-dione (15 microM) abolished the galanin-evoked
      cyclic GMP response in the hippocampus. Inhibitors of nitric oxide synthase, L
      Arg(NO2)-OMe.HCl and 7-nitroindazole monosodium salt, applied locally, blocked
      the galanin-induced increase in hippocampal extracellular cyclic GMP. This
      increase was also prevented by local application of 1H-(1,2,4)oxadiazolo(4,3a)
      quinoxalin-1-one, a selective inhibitor of soluble guanylyl cyclase. The galanin
      receptors mediating the rise in cyclic GMP reside outside the hippocampus, as
      galanin (0.35-3 nmol) locally applied had no effect. The results provide in vivo
      evidence that galanin stimulates the N-methyl-D-aspartate receptor/nitric oxide
      synthase/cyclic GMP pathway in the ventral hippocampus, which may be of
      importance in memory processes.

PMID- 9639276
TI  - On the role of galanin in mediating spinal flexor reflex excitability in
      inflammation.
AB  - The effects of exogenous and endogenous galanin on spinal flexor reflex
      excitability was evaluated in rats one to eight days after the induction of
      inflammation by subcutaneous injection of carrageenan into the sural nerve
      innervation area. In normal rats, electrical stimulation of C-fibres in the sural
      nerve elicited a brisk reflex discharge. Conditioning stimulation of C-fibres
      (1/s) generated a gradual increase in reflex magnitude (wind-up), which was
      followed by a period of reflex hyperexcitability. Intrathecal galanin dose
      dependently blocked reflex hyperexcitability induced by C-fibre conditioning
      stimulation whereas i.t. M-35, a high-affinity galanin receptor antagonist,
      moderately potentiated this effect. At one to three days after the injection of
      carrageenen, when inflammation was at its peak, the magnitude of the reflex was
      significantly increased and discharge duration became prolonged. However, wind-up
      and reflex hyperexcitability were significantly reduced. Furthermore, reduced
      reflex excitability during conditioning stimulation ("wind-down") and depression
      of the reflex were sometimes present, which are rarely observed in normal rats.
      Intrathecal galanin reduced hyperexcitability during inflammation, although its
      potency was weaker than in normals. However, the galanin receptor antagonist M-35
      strongly enhanced wind-up and reflex hyperexcitability, similarly as in normal
      rats. The baseline flexor reflex, wind-up and C-fibre conditioning stimulation
      induced facilitation were normalized four to eight days after carrageenan
      injection when signs of inflammation were diminishing. Interestingly, intrathecal
      galanin and M-35 failed to influence spinal excitability. The results suggest a
      complex functional plasticity in the role of endogenous galanin in mediating
      spinal excitability during inflammation. There appears to be an enhanced
      endogenous inhibitory control by galanin on C-afferent input during the peak of
      inflammation, which may explain the relative ineffectiveness of exogenous
      galanin. During the recovery phase there may be a reduction in galanin receptors,
      which may impair the action of endogenous and exogenous galanin. These results
      further support the notion that galanin is an endogenous inhibitory peptide in
      nociception.

PMID- 9639277
TI  - Apposition of enkephalin- and neurotensin-immunoreactive neurons by serotonin
      immunoreactive varicosities in the rat spinal cord.
AB  - The descending serotonergic system provides a powerful inhibitory input to the
      dorsal horn of the spinal cord. Little is known about the chemical identity of
      the spinal neurons that the serotonergic system innervates, although spinal
      enkephalinergic neurons are likely candidates. This study investigated the
      apposition of serotonin-immunoreactive varicosities onto enkephalin- and
      neurotensin-immunoreactive neurons in the rat lumbosacral spinal cord. Using a
      double immunofluorescence technique, serotonin-immunoreactive varicosities were
      observed to abut the soma or proximal dendrites of [Met]enkephalin- and
      neurotensin-immunoreactive neurons. Nearly 75% of all [Met]enkephalin- and
      neurotensin-immunoreactive neurons were apposed by serotonin-immunoreactive
      varicosities in the marginal zone and dorsal gray commissure. In substantia
      gelatinosa, approximately half of the [Met]enkephalin- and neurotensin
      immunoreactive neurons were juxtaposed by serotonin-immunoreactive varicosities.
      [Met]enkephalin-immunoreactive neurons also were bordered by serotonin
      immunoreactive varicosities in the nucleus proprius (65%) and sacral
      parasympathetic nucleus (75%). The results of this study suggest that the
      descending serotonergic system mediates nociception via probable contacts with
      intrinsic enkephalin and neurotensin spinal systems. The mode of action of spinal
      serotonin on enkephalin and neurotensin neurons may be through "volume"
      transmission vs synaptic or "wiring" transmission.

PMID- 9639278
TI  - Reduced nicotinamide adenine dinucleotide phosphate diaphorase in the spinal cord
      of dogs.
AB  - The distribution of somatic, fibre-like and punctate, non-somatic reduced
      nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase activity was
      examined in dog spinal cord using horizontal, sagittal and transverse sections.
      The morphological features of NADPH diaphorase exhibiting neurons divided into
      six different neuronal types (N1-N6) were described and their laminar
      distribution specified. Major cell groups were identified in the superficial
      dorsal horn and around the central canal at all spinal levels, and in the
      intermediolateral cell column at thoracic level. NADPH diaphorase exhibiting
      neurons of the pericentral region were distributed in a thin subependymal cell
      column containing longitudinally-arranged small bipolar neurons with processes
      penetrating deeply into the intermediolateral cell column and/or running
      rostrocaudally in the subependymal layer. The second pericentral cell column
      located more laterally in lamina X contains large, intensely-stained NADPH
      diaphorase exhibiting neurons with long dendrites radiating in the transverse
      plane. Neurons of the sacral parasympathetic nucleus seen in segments S1-S3
      exhibited prominent NADPH diaphorase activity accompanied by heavily-stained
      fibres extending from Lissauer's tract through lamina I along the lateral edge of
      the dorsal horn to lamina V. A massive dorsal gray commissure, with high NADPH
      diaphorase activity, was found in segments S1-S3. At the same segmental level a
      prominent group of moderately-stained motoneurons was detected in the
      dorsolateral portion of the anterior horn. Fibre-like NADPH diaphorase activity
      was found in the superficial dorsal horn and pericentral region in all segments
      studied. Punctate, non-somatic NADPH diaphorase activity was detected in the
      superficial dorsal horn, in the pericentral region all along the rostrocaudal
      axis and in the nucleus phrenicus (segments C4-C5), nucleus dorsalis (segments
      Th2-L2), nucleus Y (segments S1-S3), and the dorsal part of the dorsal gray
      commissure (S1-S3). A schematic diagram documenting the segmental and laminar
      distribution of NADPH diaphorase activity is given.

PMID- 9639279
TI  - Identification of lamina V and VII interneurons presynaptic to adrenal
      sympathetic preganglionic neurons in rats using a recombinant herpes simplex
      virus type 1.
AB  - Although indirect evidence suggests that the control of sympathetic preganglionic
      neurons is mediated to a great extent through interneurons, little is known about
      the location, morphology or neurotransmitter phenotype of such interneurons. This
      limitation seriously impedes our understanding of spinal synaptic circuits
      crucial to control of arterial pressure and other visceral functions. We used a
      highly neurotropic, minimally cytopathic recombinant herpes simplex virus type-1
      to study spinal "sympathetic" interneurons labelled by trans-synaptic transport
      of the virus from the adrenal gland in rats. Approximately 120-320 infected
      neurons/rat were identified by immunocytochemical detection of the viral antigen.
      We distinguished between virus-infected preganglionic neurons and infected
      interneurons by (i) their location within the spinal laminae, (ii) their size and
      shape and (iii) the presence or absence of immunoreactivity for the acetylcholine
      synthesizing enzyme, choline acetyltransferase, a marker of sympathetic
      preganglionic neurons. Virus-labelled sympathetic preganglionic neurons were
      found within the known spinal preganglionic nuclei. Non-cholinergic, virus
      labelled neurons were located throughout lamina VII and in the ventral portion of
      lamina V. These putative interneurons were found in the major spinal
      preganglionic nuclei, usually intermingled with the preganglionic neurons.
      Sometimes, they were located in clusters separate from the preganglionic neurons.
      The interneurons were approximately 15 microm in diameter, smaller than the
      average preganglionic neuron (diameter=25 microm), and had a few fine processes
      emanating from them. These non-cholinergic interneurons constituted approximately
      one-half of the population of virus-infected neurons. In summary, with the use of
      a recombinant herpes simplex virus, we identified a large number of non
      cholinergic interneurons close to, or intermingled with, adrenal sympathetic
      preganglionic neurons. The neurotransmitter phenotype of these neurons remains to
      be determined but they likely integrate much of the supraspinal and primary
      afferent inputs to spinal preganglionic neurons that control arterial pressure
      and other visceral functions.

PMID- 9639280
TI  - Differential regulation of the cloned kappa and mu opioid receptors.
AB  - To directly compare the regulation of the cloned kappa and mu opioid receptor, we
      expressed them in the same cells, the mouse anterior pituitary cell line AtT-20.
      The coupling of an endogenous somatostatin receptor to adenylyl cyclase and an
      inward rectifier K+ current has been well characterized in these cells, enabling
      us to do parallel studies comparing the regulation of both the kappa and the mu
      receptor to this somatostatin receptor. We show that the kappa receptor readily
      uncoupled from the K+ current and from adenylyl cyclase after a 1 h pretreatment
      with agonist, as indicated by the loss in the ability of the agonist to induce a
      functional response. The desensitization of the kappa receptor was homologous, as
      the ability of somatostatin to mediate inhibition of adenylyl cyclase or
      potentiation of the K+ current was not altered by kappa receptor desensitization.
      The mu receptor uncoupled from the K+ current but not adenylyl cyclase after a 1
      h pretreatment with agonist. Somatostatin was no longer able to potentiate the K+
      current after mu receptor desensitization, thus this desensitization was
      heterologous. Interestingly, pretreatment with a somatostatin agonist caused
      uncoupling of the mu receptor but not the kappa receptor from the K+ current.
      These results show that in the same cell line, after a 1 h pretreatment with
      agonist, the kappa receptor displays homologous regulation, whereas the mu
      receptor undergoes only a heterologous form of desensitization. mu receptor
      desensitization may lead to the alterations of diverse downstream events, whereas
      kappa receptor regulation apparently occurs at the level of the receptor itself.
      Broad alterations of non-opioid systems by the mu receptor could be relevant to
      the addictive properties of mu agonists. Comparison of kappa and mu receptor
      regulation may help define the properties of the mu receptor which are important
      in the development of addiction, tolerance, and withdrawal to opioid drugs. These
      are the first studies to directly compare the coupling of the kappa and mu
      receptors to two different effectors in the same mammalian expression system.

PMID- 9639281
TI  - Pharmacological, molecular and functional characterization of vasoactive
      intestinal polypeptide/pituitary adenylate cyclase-activating polypeptide
      receptors in the rat pineal gland.
AB  - Melatonin secretion from the mammalian pineal gland is strongly stimulated by
      noradrenaline and also by vasoactive intestinal polypeptide (VIP) and pituitary
      adenylate cyclase-activating polypeptide (PACAP). Three types of receptors for
      VIP and PACAP have been characterized so far: VIP1/PACAP receptors and VIP2/PACAP
      receptors, which possess similar high affinities for VIP and PACAP, and PACAP1
      receptors which exhibit a 100-1000-fold higher affinity for PACAP. The aim of the
      present study was to characterize the receptor subtype(s) mediating the
      stimulatory effects of VIP and PACAP on melatonin synthesis in the rat pineal
      gland. Autoradiographic studies showed that PACAP and VIP were equally potent in
      displacing binding of radioiodinated PACAP27 from pineal sections. Amplification
      of pineal complementary DNAs by polymerase chain reaction using specific primers
      for the different receptor subtypes revealed that all three receptor messenger
      RNAs are expressed and that VIP1/PACAP receptor messenger RNA was predominant
      over VIP2/PACAP receptor messenger RNA. In vitro, VIP and PACAP stimulated
      melatonin synthesis with similar high potency and the effect of the two peptides
      were not additive. The selective VIP1/PACAP receptor agonists [R16]chicken
      secretin (1-25) and [K15, R16, L27]VIP(1-7)/growth hormone releasing factor(8-27)
      were significantly more potent than the selective VIP2/PACAP receptor agonist RO
      25-1553 in stimulating melatonin secretion. The stimulatory effects of VIP and
      PACAP were similarly inhibited by the VIP1/PACAP antagonist [acetyl-His1, D-Phe2,
      K15, R16, L27]VIP(3-7)/growth hormone releasing factor(8-27). These data strongly
      suggest that VIP and PACAP exert a stimulatory effect on melatonin synthesis
      mainly through activation of a pineal VIP1/PACAP receptor subtype.

PMID- 9639282
TI  - Quantitative immunolocalization of mu opioid receptors: regulation by naltrexone.
AB  - The present study utilized a newly developed quantitative immunohistochemical
      assay to measure changes in mu opioid receptor abundance following chronic
      administration of the opioid receptor antagonist naltrexone. These data were
      compared with those obtained from mu receptor radioligand binding on adjacent
      tissue sections, in order to determine whether the characteristic antagonist
      induced increase in radioligand binding is due to an increase in the total number
      of mu receptors and/or to an increase in the proportion of receptors that are in
      an active binding conformation in the absence of a change in the total number of
      receptors. Adult male Sprague-Dawley rats were administered naltrexone, 7-8 mg/kg
      per day, or saline continuously for seven days by osmotic minipumps, after which
      time their brains were processed for immunohistochemistry and receptor
      autoradiography on adjacent fresh frozen tissue sections. Semiquantitative
      immunohistochemistry was performed using a radiolabelled secondary antibody for
      autoradiographic determination and a set of radioactive standards. Results
      demonstrate an overall concordance between the distribution of mu opioid
      receptors as measured by the two different methods with a few exceptions.
      Following naltrexone administration, mu receptor immunoreactivity was
      significantly higher in the amygdala, thalamus, hippocampus, and interpeduncular
      nucleus as compared with the saline-treated control animals. [3H]D-Ala2,N-Me
      Phe4,Gly-ol5-enkephalin binding to mu opioid receptors was significantly higher
      in the globus pallidus, amygdala, thalamus, hypothalamus, hippocampus, substantia
      nigra, ventral tegmental area, central gray, and interpeduncular nucleus of the
      naltrexone-treated rats. These findings indicate that in some brain regions
      chronic naltrexone exposure increases the total number of mu opioid receptors,
      while in other regions there is an increase in the percent of active receptors
      without an observable change in the total number of receptors. Quantitative
      receptor immunodetection together with ligand autoradiography provides a new
      approach for investigating the regulation of mu opioid receptors on tissue
      sections.

PMID- 9639283
TI  - Attenuation of 6-hydroxydopamine-induced dopaminergic nigrostriatal lesions in
      superoxide dismutase transgenic mice.
AB  - 6-Hydroxydopamine is a neurotoxin that produces degeneration of the nigrostriatal
      dopaminergic pathway in rodents. Its toxicity is thought to involve the
      generation of superoxide anion secondary to its autoxidation. To examine the
      effects of the overexpression of Cu,Zn-superoxide dismutase activity on 6
      hydroxydopamine-induced dopaminergic neuronal damage, we have measured the
      effects of 6-hydroxydopamine on striatal and nigral dopamine transporters and
      nigral tyrosine hydroxylase-immunoreactive neurons in Cu,Zn-superoxide dismutase
      transgenic mice. Intracerebroventricular injection of 6-hydroxydopamine (50
      microg) in non-transgenic mice produced reductions in the size of striatal area
      and an enlargement of the cerebral ventricle on both sides of the brains of mice
      killed two weeks after the injection. In addition, 6-hydroxydopamine caused
      marked decreases in striatal and nigral [125I]RTI-121-labelled dopamine
      transporters not only on the injected side but also on the non-injected side of
      non-transgenic mice; this was associated with decreased cell number and size of
      tyrosine hydroxylase-immunoreactive dopamine neurons in the substantia nigra pars
      compacta on both sides in these mice. In contrast, superoxide dismutase
      transgenic mice were protected against these neurotoxic effects of 6
      hydroxydopamine, with the homozygous transgenic mice showing almost complete
      protection. These results provide further support for a role of superoxide anion
      in the toxic effects of 6-hydroxydopamine. They also provide further evidence
      that reactive oxygen species may be the main determining factors in the
      neurodegenerative effects of catecholamines.

PMID- 9639284
TI  - Rat striatal adenosinergic modulation of ethanol-induced motor impairment:
      possible role of striatal cyclic AMP.
AB  - We have previously reported the involvement of the striatum in acute ethanol
      induced motor incoordination and the striatal adenosinergic modulation of ethanol
      induced motor incoordination through A1 receptor-mediated mechanism(s). The
      present study, a continuation of our previous work, was carried out to
      investigate the possible functional correlation between striatal cyclic AMP and
      ethanol-induced motor incoordination, and its modulation by striatal adenosine in
      Sprague-Dawley rats. Forskolin (0.1, 0.5 and 1.0 pmol), a known activator of
      adenylate cyclase, significantly attenuated ethanol-induced motor incoordination
      in a dose-dependent manner following its direct intrastriatal microinfusion.
      Forskolin also antagonized the accentuating effect of intrastriatal N6
      cyclohexyladenosine on ethanol-induced motor incoordination. These results
      suggested that ethanol-induced motor incoordination might be functionally
      correlated to a decrease in the striatal cyclic AMP levels and that the striatal
      adenosine A1 receptors might modulate ethanol-induced motor incoordination
      through cyclic AMP signaling mechanism(s). Further support to this hypothesis was
      obtained by the actual measurement of the striatal cyclic AMP levels in the same
      experimental conditions as in motor coordination studies using high-performance
      liquid chromatography with fluoroscence detection. Regardless of the method
      (focused microwave irradiation, cervical dislocation or decapitation into a dry
      ice-ethanol mixture) used to kill the animals, a significant decrease in the
      striatal cyclic AMP levels was observed due to ethanol. Intrastriatal adenosine
      A1-selective agonist, N6-cyclohexyladenosine (24 ng), caused a further
      significant decrease in the striatal cyclic AMP levels in the ethanol- but not in
      the vehicle-treated animals. The further enhancement in the ethanol-induced
      decrease in the striatal cyclic AMP levels by intrastriatal N6
      cyclohexyladenosine, therefore, functionally correlated with the observed
      potentiating effect of intrastriatal N6-cyclohexyladenosine on ethanol-induced
      motor incoordination. The effects of intrastriatal N6-cyclohexyladenosine+ethanol
      and of ethanol alone on the striatal cyclic AMP levels were blocked by
      intrastriatal pertussis toxin (500 ng) pretreatment, indicating the involvement
      of pertussis toxin-sensitive G-proteins (Gi, Go) and possibly of the adenosine A1
      receptor coupled to the G-proteins in the striatum. Furthermore, ethanol alone
      significantly decreased the basal as well as the cyclic AMP-stimulated catalytic
      activities of the striatal cyclic AMP protein kinase, which were further reduced
      by intrastriatal N6-cyclohexyladenosine. The results of the present study
      therefore support an involvement of a cyclic AMP signaling pathway in the
      striatal adenosinergic modulation of ethanol-induced motor incoordination at the
      post-adenosine A1 receptor level.

PMID- 9639285
TI  - Riluzole interacts with voltage-activated sodium and potassium currents in
      cultured rat cortical neurons.
AB  - The actions of the neuroprotective and anticonvulsant agent riluzole on voltage
      activated currents were studied in primary cultures of rat cortical neurons by
      using whole-cell patch-clamp recording techniques. Isolated Na+, Ca2+ and K+
      currents were generated in these cells by depolarizing commands from a holding
      potential of - 80 mV. Riluzole (10-300 microM) reversibly reduced in a dose
      dependent manner the inward Na+ currents with an IC50 of 51 microM in all the
      tested neurons (n=29). This drug also shifted the steady-state inactivation curve
      of the sodium current towards more negative values (about 20mV, n=15) while it
      did not change significantly the decay phase of the Na+ current. Furthermore,
      riluzole (100 and 300 microM; n=5 and n=3, respectively) did not modulate the
      inward Ca2+ currents evoked by depolarizing steps on cortical cells. An
      additional concentration-dependent effect of riluzole was observed on the outward
      potassium currents. In fact, while the amplitude of the peak of the outward
      current (IA) was not changed significantly, the amplitude of the late component
      of the outward K+ current (Iss) was markedly decreased during the perfusion of
      riluzole (IC50=88 microM; n=16). It is concluded that riluzole modulates the Na+-
      and the late K+-dependent currents in cortical neurons. Both phenomena may
      explain, at least in part, the anticonvulsant and neuroprotective properties of
      this compound.

PMID- 9639287
TI  - Comparison of vesicular volume and quantal size in bovine chromaffin cells.
AB  - Electrochemical measurements of vesicular content released were compared with the
      morphometric measurements of vesicular size in bovine chromaffin cells. Cross
      sectional vesicular diameters were determined from electron micrographs. Two
      methods were used to determine the frequency histograms of "true" vesicular
      diameters (i.e. diameters of the vesicles in the equatorial plane): (i) "peeling
      off" method [Coupland R. E. (1968), Nature 217, 384-388], and (ii) summation of
      individual probabilities of "true" vesicular diameters. Quantal size was
      estimated from the area under the spontaneous current spike detected
      electrochemically. The frequency histograms of "true" vesicular diameters are
      found to be skewed (thus not well described by a Gaussian function) irrespective
      of the method used to calculate them, as are the frequency histograms of the cube
      roots of the quantal sizes. Furthermore, we also find that the frequency
      histograms of electrochemical measurements (the cube roots of quantal sizes) have
      lower skews and coefficients of variation than those of morphometric measurements
      ("true" vesicular diameters), with discrepancy being especially pronounced for
      noradrenaline-secreting cells. Such a difference in both coefficients of
      variation and skews suggests that the intravesicular catecholamine concentration
      is not uniform, but that it is lower for vesicles of larger size. In conclusion a
      variety of factors--vesicular volume, vesicular surface area to volume ratio,
      binding capacity of chromogranin and/or ATP, likely determines the amount of
      catecholamine stored in the vesicle.

PMID- 9639286
TI  - Mu-opioid and GABA(B) receptors modulate different types of Ca2+ currents in rat
      nodose ganglion neurons.
AB  - Whole-cell patch-clamp recordings were obtained from nodose ganglion neurons
      acutely dissociated from 10-30-day-old rats to characterize the Ca2+ channel
      types that are modulated by GABA(B) and mu-opioid receptors. Five components of
      high-threshold current were distinguished on the basis of their sensitivity to
      blockade by omega-conotoxin GVIA, nifedipine, omega-agatoxin IVA and omega
      conotoxin MVIIC. Administration of the mu-opioid agonist H-Tyr-D-Ala-Gly-Phe(N
      Me)-Gly-ol (0.3-1 mM) or the GABA(B) agonist baclofen in saturating
      concentrations suppressed high-threshold Ca2+ currents by 49.9+/-2.4% (n=69) and
      18.7+/-2.1% (n=35), respectively. The inhibition by H-Tyr-D-Ala-Gly-Phe(N-Me)-Gly
      ol exceeded that by baclofen in virtually all neurons that responded to both
      agonists (67%), and occlusion experiments revealed that responses to mu-opioid
      and GABA(B) receptor activation were not linearly additive. In addition,
      administration of staurosporine, a non-selective inhibitor of protein kinase A
      and C, did not affect the inhibitory responses to either agonist or prevent the
      occlusion of baclofen-induced current inhibition by H-Tyr-D-Ala-Gly-Phe(N-Me)-Gly
      ol. Blockade of N-type channels by omega-conotoxin GVIA eliminated current
      suppression by baclofen in all cells tested (n=11). Mu-opioid-induced inhibition
      in current was abolished by omega-conotoxin GVIA in 12 of 30 neurons tested, but
      was only partially reduced in the remaining 18 neurons. In the latter cells
      administration of omega-agatoxin IVA reduced, but did not eliminate the mu-opioid
      sensitive current component that persisted after blockade of N-type channels.
      This residual component of mu-opioid-sensitive current was blocked completely by
      omega-conotoxin MVIIC in nine neurons, whereas responses to H-Tyr-D-Ala-Gly-Phe(N
      Me)-Gly-ol were still recorded in the remaining cells after administration of
      these Ca2+ channel toxins and nifedipine. Dihydropyridine-sensitive (L-type)
      current was not affected by activation of mu-opioid or GABA(B) receptors in any
      of the neurons. These data indicate that in nodose ganglion neurons mu-opioid
      receptors are negatively coupled to N-, P- and Q-type channels as well as to a
      fourth, unidentified toxin-resistant Ca2+ channel. In contrast, GABA(B) receptors
      are coupled only to N-type channels. Furthermore, the results do not support a
      role for either protein kinase C or A in the modulatory pathway(s) coupling mu
      opioid and GABA(B) receptors to Ca2+ channels, but rather lend credence to the
      notion that the signalling mechanisms utilized by these two receptors might
      simply compete for inhibitory control of a common pool of N-type channels.

PMID- 9639288
TI  - Activity-dependent regulation of dopamine content in the olfactory bulbs of naris
      occluded rats.
AB  - Several lines of evidence strongly suggest that reduced olfactory nerve activity
      results in decreased bulb dopamine content. In the present study, high
      performance liquid chromatography with electrochemical detection was used to
      assess catecholamine levels in bulbs from postnatal day 60 rats that had
      undergone either unilateral naris cautery or a sham surgery on day 30. Thirty
      days of odor deprivation dramatically reduced dopamine and dihydroxyphenylacetic
      acid levels in functionally-deprived bulbs (ipsilateral to occluded nares) as
      compared to contralateral controls, while norepinephrine and
      dihydroxyphenylglycol levels were unchanged. The loss of dopamine was more severe
      in medial as compared to lateral aspects of experimental bulbs, while the loss of
      dihydroxyphenylacetic acid was similar on the two sides. To test directly the
      hypothesis that afferent activity regulates dopamine and dihydroxyphenylacetic
      acid content, 1 h of high frequency tetanic nerve stimulation was provided to the
      rostral-medial olfactory nerve layer in deprived olfactory bulbs, and
      catecholamine levels were assessed from 6 to 192 h later. Partial and temporary
      recovery of dopamine was observed in medial aspects of the bulb when rats were
      examined 96 h later, while consistent recovery of dihydroxyphenylacetic acid
      content was not apparent. These data corroborate evidence that olfactory nerve
      activity is a potent regulator of bulb dopamine and indicate that continued
      afferent input is necessary to maintain dopamine levels.

PMID- 9639289
TI  - Modulation of gamma-aminobutyric acid (GABA) receptors and the feeding response
      by neurosteroids in Hydra vulgaris.
AB  - Gamma-Aminobutyric acid (GABA) receptors are present in membrane preparations
      from Hydra vulgaris, one of the most primitive organisms with a nervous system.
      These receptors are sensitive to muscimol and benzodiazepines and appear to be
      important in the regulation of the feeding response. The effects of
      neurosteroids, general anaesthetics, and GABA antagonists on GABA(A) receptors in
      membranes prepared from Hydra and on the feeding response have now been
      investigated. The neurosteroids tetrahydroprogesterone and
      tetrahydrodeoxycorticosterone increased [3H]GABA binding to hydra membranes with
      nanomolar potency (EC50, 141+/-11 and 623+/-36 nM, respectively) and high
      efficacy (maximal increase 79+/-6.5 and 62+/-4%, respectively), whereas the 3beta
      hydroxy epimer of tetrahydroprogesterone was ineffective. The benzodiazepine
      receptor ligands diazepam (100 microM), clonazepam (100 microM) and abecarnil (30
      microM) enhanced [3H]GABA binding to Hydra membranes by 22, 20 and 24%,
      respectively; effects abolished by the specific benzodiazepine antagonist
      flumazenil (100 microM). On the contrary, the peripheral benzodiazepine receptor
      ligand 4'chlorodiazepam failed to affect [3H]GABA binding to Hydra membranes. The
      general anaesthetics propofol and alphaxalone similarly increased (+38% and +30%
      respectively) [3H]GABA binding. Moreover, [3H]GABA binding to Hydra membranes was
      completely inhibited by the GABA(A) receptor antagonist SR 95531, whereas
      bicuculline was without effect. The modulation of GABA(A) receptors in vitro by
      these various drugs correlated with their effects on the glutathione-induced
      feeding response in the living animals. Tetrahydroprogesterone and
      tetrahydrodeoxy-corticosterone (1 to 10 microM) prolonged, in a dose-dependent
      manner, the duration of mouth opening induced by 10 microM glutathione, with
      maximal effects of +33 and +29%, respectively, apparent at 10 microM
      neurosteroid. Alphaxalone (10 microM) similarly increased (+33%) the effect of
      glutathione. The effects of steroids on the feeding response were inhibited by SR
      95531 in a dose-dependent manner; t-butylbyclophosphorothyonate (1 microM), a
      specific Cl- channel blocker, which per se, like picrotoxin but not bicuculline,
      shortened the duration of the response, also counteracted the steroids effects at
      1 microM. These results suggest that the modulation of GABA(A) receptors by
      steroids is an ancient characteristic of the animal kingdom and that the
      pharmacological properties of these receptors have been highly conserved through
      evolution.

PMID- 9639290
TI  - Differential effect of protein kinase inhibitors on calcium-dependent and calcium
      independent [14C]GABA release from rat brain synaptosomes.
AB  - Rat brain synaptosomes were isolated to study the effects of protein kinase
      inhibitors (sphingosine, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine
      dihydrochloride, N-(6-aminohexyl)-5-chloro-1-naphtalenesulfonamide,
      staurosporine) on Ca2+-dependent and Ca2+-independent [14C]GABA release. The Ca2+
      dependent [14C]GABA release was stimulated by depolarization with a K+-channel
      blocker, 4-aminopyridine, or high K+ concentration. It has been shown that 4
      aminopyridine-evoked [14C]GABA release strongly depends on extracellular Ca2+
      while K+-evoked [14C]GABA release only partly decreases in the absence of
      calcium. The substitution of sodium by choline in Ca2+-free medium completely
      abolished Ca2+-independent part of K+-evoked [14C]GABA release. So the main
      effect of 4-aminopyridine is the Ca2+-dependent one while high K+ is able to
      evoke [14C]GABA release in both a Ca2+-dependent and Na+-dependent manner. In
      experiments with protein kinase inhibitors, 4-aminopyridine and high K+
      concentration were used to study the Ca2+-dependent and the Ca2+-independent
      [14C]GABA release, respectively. In addition, the Ca2+-independent [14C]GABA
      release was studied using alpha-latrotoxin as a tool. Pretreatment of
      synaptosomes with protein kinase inhibitors tested, except of 1-(5
      isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride, resulted in a marked
      inhibition of 4-aminopyridine-stimulated Ca2+-dependent [14C]GABA release. The
      inhibitory effects of N-(6-aminohexyl)-5-chloro-1-naphtalenesulfonamide and
      staurosporine on [14C]GABA release were not due to their effects on 4
      aminopyridine-promoted 45Ca2+ influx into synaptosomes. Only sphingosine (100
      microM) reduced the 45Ca2+ influx. All the inhibitors investigated were
      absolutely ineffective in blocking the Ca2+-independent [14C]GABA release
      stimulated by alpha-latrotoxin. Three of them, except for sphingosine, did not
      affect the Ca2+-independent [14C]GABA release stimulated by high potassium. The
      inhibitory effect of sphingosine was equal to 30%. Thus, if [14C]GABA release
      occurred in a Ca2+-independent manner irrespective of whether alpha-latrotoxin or
      high K+ stimulated this process, it was not inhibited by the drugs decreased the
      Ca2+-dependent [14C] GABA release. Given the above points it is therefore not
      unreasonable to assume that the absence of Ca2+ in the extracellular medium
      created the conditions in which the activation of neurotransmitter release was
      not accompanied by Ca2+-dependent dephosphorylation of neuronal phosphoproteins,
      and as a consequence the regulation of exocytotic process was modulated so that
      the inhibition of protein kinases did not disturb the exocytosis.

PMID- 9639291
TI  - FDG accumulation and tumor biology.
AB  - The tumoral uptake of fluorine-18-deoxyglucose (FDG) is based upon enhanced
      glycolysis. Following injection, FDG is phosphorylated and trapped
      intracellularly. An important mechanism to transport FDG into the transformed
      cell is based upon the action of glucose transporter proteins; furthermore,
      highly active hexokinase bound to tumor mitochondria helps to trap FDG into the
      cell. In addition, enhanced FDG uptake may be due to relative hypoxia in tumor
      masses, which activates the anaerobic glycolytic pathway. In spite of these
      processes, FDG uptake is relatively aspecific since all living cells need
      glucose. Clinical use is therefore recommended in carefully selected patients.

PMID- 9639292
TI  - Electrophysiological study, biodistribution in mice, and preliminary PET
      evaluation in a rhesus monkey of 1-amino-3-[18F]fluoromethyl-5-methyl-adamantane
      (18F-MEM): a potential radioligand for mapping the NMDA-receptor complex.
AB  - The effect of the fluorinated memantine derivative and NMDA receptor antagonist,
      1-amino-3-fluoromethyl-5-methyl-adamantane (19F-MEM), at the NMDA receptor ion
      channel was studied by patch clamp recording. The results showed that 19F-MEM is
      a moderate NMDA receptor channel blocker. A procedure for the routine preparation
      of the 18F-labelled analog 18F-MEM has been developed using a two-step reaction
      sequence. This involves the no-carrier-added nucleophilic radiofluorination of 1
      [N-(tert-butyloxy)carbamoyl]-3-(toluenesulfonyloxy)methyl- 5-methyl-adamantane
      and the subsequent cleavage of the BOC-protecting group using aqueous HCI. The
      18F-MEM was obtained in 22 +/- 7% radiochemical yield (decay-corrected to EOB) in
      a total synthesis time including HPLC purification of 90 min. A biodistribution
      study after i.v. injection of 18F-MEM in mice showed a fast clearance of
      radioactivity from blood and relatively high initial uptake in the kidney and in
      the lung, which gradually decreased with time. The brain uptake was high (up to
      3.6% ID/g, 60 min postinjection) with increasing brain-blood ratios: 2.40, 5.10,
      6.33, and 9.27 at 5, 30, 60, and 120 min, respectively. The regional accumulation
      of the radioactivity in the mouse brain was consistent with the known
      distribution of the PCP recognition site. Preliminary PET evaluation of the
      radiotracer in a rhesus monkey demonstrated good uptake and prolonged retention
      in the brain, with a plateau from 35 min onwards p.i. in the NMDA receptor-rich
      regions (frontal cortex, striata, and temporal cortex). Delineation of the
      hippocampus, a region known to contain a high density of NMDA receptors, was not
      possible owing to the resolution of the PET tomograph. The regional brain uptake
      of 18F-MEM was changed by memantine and by a pharmacological dose of (+)-MK-801,
      indicating competition for the same binding sites. In a preliminary experiment,
      haloperidol, a dopamine D2 and sigma receptor antagonist, decreased the binding
      of 18F-MEM from the brain regions examined, suggesting that binding was also
      occurring to the sigma recognition sites.

PMID- 9639293
TI  - Exploration of the dopamine transporter: in vitro and in vivo characterization of
      a high-affinity and high-specificity iodinated tropane derivative (E)-N-(3
      iodoprop-2-enyl)-2beta-carbomethoxy-3beta-(4'-m ethylph enyl)nortropane (PE2I).
AB  - For the diagnosis and follow-up of neurodegenerative diseases, many cocaine
      derivatives have been proposed as radioligands to explore the dopamine
      transporter. As none of them have all the criteria of specificity and kinetics
      for human use, we have developed a new derivative, (E)-N-(3-iodoprop-2-enyl)
      2beta-carbomethoxy-3beta-(4'-methy lphenyl)nortropane (PE2I), which displays
      promising properties. We report the characterization of PE2I in vitro on rat
      striatal membranes and in vivo in rats and in monkeys. PE2I had a high affinity
      (Kd = 0.09 +/- 0.01 nM) and high specificity for the dopamine transporter. In
      rats we observed a high accumulation in the striatum; by contrast, a very low
      fixation was measured in the cortex. Moreover, a preinjection of a saturating
      dose of GBR 12909 prevented the striatal accumulation of PE2I by 74%. These
      results confirmed the specificity of PE2I for the dopamine transporter. In vivo
      in monkeys, SPECT studies showed a high accumulation in striatum. Moreover, an
      equilibrium state was obtained 1 h after injection. PE2I seemed to be the most
      promising ligand for the dopamine transporter exploration by SPECT using a single
      day protocol.

PMID- 9639294
TI  - Synthesis and characterization of a 11C-labelled derivative of S12968: an attempt
      to image in vivo brain calcium channels.
AB  - [11C]S11568 (3-ethyl-5-methyl 2-[2-(2-aminoethoxy)ethoxymethyl]-4-(2,3
      dichlorophenyl)-6-methyl- 1,4-dihydropyridine-3,5-dicarboxylate) is a powerful
      ligand for the visualization of the cardiac calcium channel in vivo using PET.
      The aim of the present study was to synthesize a lipophilic, nonionized
      derivative of S11568 to facilitate its penetration into the brain. To increase
      the lipophilicity and to remove simultaneously the ionic nature of our ligand,
      the N-tert-butoxycarbonyl (N-Boc) derivative of S11568 was synthesized. An IC50
      value of 1.7 nM for this derivative confirmed that both the affinity and
      selectivity for the calcium channel was unaltered by this chemical modification
      (S11568 with IC50 value of 9.9 nM). The biologically more active enantiomer of
      S11568, the levogyre isomer S12968, was labelled with 11C using [11C]iodomethane.
      The lipophilicity of the N-Boc derivative was increased by a factor of three to
      four when compared to the parent compound (as determined by the measurement of
      the octanol/buffer partition coefficients). In vivo, this derivative slightly
      crosses the blood-brain barrier, as demonstrated by a 4-fold increase (with
      respect to the parent compound S12968) of the radioactivity in the brain using
      the 11C-labelled N-Boc S12968. This uptake remained too low to be suitable for
      imaging calcium channels.

PMID- 9639295
TI  - High-yield radiosynthesis and preliminary in vivo evaluation of p-[18F]MPPF, a
      fluoro analog of WAY-100635.
AB  - No-carrier-added 4-[18F]fluoro-N-[2-[1-(2-methoxyphenyl)-1 piperazinyl]ethyl-N-2
      pyridinyl-benzamide (p-[18F]MPPF) was synthesized by nucleophilic substitution of
      the corresponding nitro compound in the presence of Kryptofix 222 and K2CO3 by
      microwave heating (3 min, 500 W) using a remotely controlled radiosynthesis.
      Baseline separation of p-[18F]MPPF from the nitro derivative was performed on a
      semipreparative HPLC C18 column. After Sep-Pak formulation, the
      radiopharmaceutical was obtained with a radiochemical yield of 25% (EOS) in about
      70 min. Specific radioactivity averaged between 1-5 Ci/micromol EOS. Labelling of
      the ortho and meta derivatives was also attempted. Brain uptake of p-[18F]MPPF
      was studied with PET on fluothane-anesthetized cats. Following intravenous
      injection of p-[18F]MPPF, high accumulation of radioactivity was observed in the
      hippocampus and cerebral cortex. Low levels of radioactivity were observed in
      cerebellum. At 30 min, the mean hippocampus/cerebellum and cortex/cerebellum
      ratios were 5 and 3.8, respectively. The accumulation of the tracer was blocked
      by prior administration of reference WAY-100635, demonstrating the specificity of
      the ligand.

PMID- 9639296
TI  - Blocking [211At]astatide accumulation in normal tissues: preliminary evaluation
      of seven potential compounds.
AB  - Normal tissue accumulation of 211At must be minimized during targeted
      radiotherapy with 211At-labeled compounds. Therefore, we investigated the ability
      of seven compounds to block normal organ uptake of [211At]astatide in mice:
      potassium iodide, sodium thiocyanate, sodium perchlorate, sodium periodate,
      cysteine, 2,3-dimercapto-1-propanesulfonic acid, and meso-2,3-dimercaptosuccinic
      acid. The monovalent anions I-, SCN-, and ClO4- reduced 211At uptake in stomach
      and thyroid, while thiocyanate and cysteine were the only compounds to
      significantly reduce activity levels in lungs and spleen. This study suggests
      that blocking agents may help reduce normal organ radiation doses in
      endoradiotherapeutic procedures with 211At-labeled radiopharmaceuticals.

PMID- 9639297
TI  - Radiosynthesis and quality assurance of 5-[124I]Iodo-2'-deoxyuridine for
      functional PET imaging of cell proliferation.
AB  - 5-[124I]Iodo-2'-deoxyuridine ([124I]IUdR) was routinely produced by direct
      electrophilic labelling of 2'-deoxyuridine with 124I of high specific activity
      (12 Ci/micromol) in an Iodogen-coated ReactiVial, followed by purification on a
      Sep-Pak C-18 cartridge. The radiochemical purity was determined by TLC on a
      Silicagel-60 plate and by reverse-phase HPLC on a RP-18 column. Based upon 45
      syntheses, the yield ranged from 45% to 65%. The radiochemical impurity of
      [124I]IUdR was determined at 2.9% by TLC (mainly iodate) and 4.3% by HPLC. The
      chemical stability of the solvated formulation allowed a time window of 2 days
      following end of synthesis (EOS) for chemical application, based upon the
      required 95% radiochemical purity grade of [124I]IUdR. The labelled compound was
      routinely used for the clinical determination of cell proliferation in glioma
      patients by positron emission tomography.

PMID- 9639298
TI  - Ganciclovir uptake in human mammary carcinoma cells expressing herpes simplex
      virus thymidine kinase.
AB  - Assessment of suicide enzyme activity would have considerable impact on the
      planning and the individualization of suicide gene therapy of malignant tumors.
      This may be done by determining the pharmacokinetics of specific substrates. We
      generated ganciclovir (GCV)-sensitive human mammary carcinoma cell lines after
      transfection with a retroviral vector bearing the herpes simplex virus thymidine
      kinase (HSV-tk) gene. Thereafter, uptake measurements and HPLC analyses were
      performed up to 48 h in an HSV-tk-expressing cell line and in a wild-type cell
      line using tritiated GCV. HSV-tk-expressing cells showed higher GCV uptake and
      phosphorylation than control cells, whereas in wild-type MCF7 cells no
      phosphorylated GCV was detected. In bystander experiments the total GCV uptake
      was related to the amount of HSV-tk-expressing cells. Furthermore, the uptake of
      GCV correlated closely with the growth inhibition (r = 0.92). Therefore, the
      accumulation of specific substrates may serve as an indicator of the HSV-tk
      activity and of therapy outcome. Inhibition and competition experiments
      demonstrated slow transport of GCV by the nucleoside carriers. The slow uptake
      and low affinity to HSV-tk indicate that GCV is not an ideal substrate for the
      nucleoside transport systems or for HSV-tk. This may be the limiting factor for
      therapy success, necessitating the search for better substrates of HSV-tk.

PMID- 9639299
TI  - Intracellular metabolism of 99mTc-d,l-HMPAO in vitro: a basic approach for
      understanding the hyperfixation mechanism in damaged brain.
AB  - The mechanism of technetium-99m-labeled d,l-hexamethylpropylene amine oxime
      (99mTc-HMPAO) hyperfixation in damaged brain was elucidated using in vitro
      metabolic studies. Among the subcellular fractions of mouse brain homogenate, the
      mitochondrial fraction showed dominant metabolic activity with respect to 99mTc
      HMPAO, followed by the cytosolic fraction. The metabolic activity of the
      mitochondrial fraction was enhanced by heat and detergent treatment, being
      proportional to the leakage of thiol (SH) compound(s) from the granules. The
      leaked SH compound(s) had a higher metabolic activity than glutathione, a well
      known reductant in cells. 99mTc-HMPAO might be metabolized by mitochondrial SH
      compound(s) exhibiting strong reductant activity, and hyperfixation might be an
      indication of mitochondrial damage of the brain.

PMID- 9639300
TI  - Cellular distribution of 111In-LDTPA galactose BSA in normal and
      asialoglycoprotein receptor-deficient mouse liver.
AB  - 111In-LDTPA galactose BSA (bovine serum albumin) was used to evaluate the
      asialoglycoprotein receptor (ASGPR) system in both normal and ASGPR-deficient
      mice. The radiolabeled glycoprotein had complete liver uptake in both normal and
      ASGPR-deficient mice. Metabolism and hepatic cell-type distribution studies were
      performed. The normal mouse excreted greater than 60% of the hepatic activity,
      while the ASGPR-deficient mouse excreted less than 40% of the hepatic activity.
      111In-LDTPA galactose BSA was metabolized to 111In-LDTPA-L-lysine in both mouse
      types. Normal mice showed 70% of the radioactivity in the hepatocyte, whereas the
      homozygous ASGPR-deficient mouse had equal activity in the hepatocyte and the
      hepatic endothelial cell.

PMID- 9639301
TI  - Similarities in the biodistribution of iodine-labeled anti-Tac single-chain
      disulfide-stabilized Fv fragment and anti-Tac disulfide-stabilized Fv fragment.
AB  - We evaluated the biodistribution and pharmacokinetics of two different iodine
      labeled Fv fragments of anti-Tac monoclonal antibody (MAb) in normal and tumor
      bearing nude mice. One was a disulfide-stabilized Fv fragment (dsFv), and the
      other was a single-chain disulfide-stabilized Fv fragment (scdsFv). The scdsFv is
      a newly developed type of Fv fragment superior to the dsFv in which the VH and VL
      are linked by covalent bonds through a spacer arm and by an internal disulfide
      bond. These modifications increase the yield of scdsFv. Both reagents recognize
      the alpha subunit of the interleukin-2 receptor (IL-2Ralpha). The biodistribution
      of the Fv fragments was evaluated in normal mice co-injected with 50 mg of L
      lysine and in a no-lysine control group. Biodistribution was also evaluated in
      nude mice bearing subcutaneous tumor xenografts derived from IL-2Ralpha-positive
      ATAC4 cells and receptor-negative A431 cells. These mice were co-injected with
      125I-labeled anti-Tac scdsFv (6 microCi/0.7 microg) and 131I-labeled anti-Tac
      dsFv (2 microCi/0.7 microg) or with 131I-labeled anti-Tac scdsFv (6 microCi/0.7
      microg) and 125I-labeled anti-Tac dsFv (4 microCi/0.7 microg). The
      biodistribution of 125I-labeled anti-Tac scdsFv and 131I-labeled anti-Tac dsFv
      was very similar in all organs and the tumors. The renal uptake of both reagents
      was blocked effectively (<93%) and similarly by lysine. The scdsFv cleared
      slightly faster from the circulation than did the dsFv because there were more
      aggregates of dsFv than of scdsFv (3% vs. 1%, respectively). The scdsFv-to-dsFv
      ratio ranged from 0.79 to 1.20 in all organs at all time points we examined. In
      conclusion, the first biodistribution study of an scdsFv molecule shows that the
      scdsFv had a biodistribution very similar to that of the dsFv and seems to be a
      good alternative to the dsFv because of its higher production yield.

PMID- 9639302
TI  - Human polyclonal immunoglobulin labelled with technetium-99m via NHS-MAG3: a
      comparison of radiochemical behavior and biological efficacy with other labelling
      methods.
AB  - The aim of this study was to evaluate the radiochemical behavior, biological
      distribution, and localization in infection sites in mice of a human polyclonal
      immunoglobulin (HIG) labelled with 99mTc by a novel MAG3-labelling method. The
      resulting [99mTc]MAG3-HIG was compared with [99mTc]HIG preparations radiolabelled
      directly via 2-mercaptoethanol (2-Me) or stannous ion (Sn) reduction and
      indirectly via 2-iminothiolane (2-Im) conjugation. All preparations showed
      similar UV and radioactivity HPLC profile to that of native HIG except for 2-Im
      HIG, which showed aggregates. The stabilities of the label to challenge with
      cysteine were similar for all the preparations. By nondenaturing SDS-PAGE, all
      preparations other than MAG3-HIG showed evidence of lower molecular weight
      fragments. The tissue distribution 4 and 24 h after intravenous administration of
      the four preparations were compared in mice previously administered with an
      isolate of Staphylococcus aureus in one thigh. The pharmacokinetics varied among
      the different preparations. When prepared via 2-Me, Sn, and 2-Im, both blood
      clearance and urinary excretion were faster than that of labelled MAG3-HIG. The
      absolute uptake in the infected thigh at 24 h was significantly higher for HIG
      labelled via MAG3 and 2-Me vs. the remaining methods. The infected thigh/normal
      thigh radioactivity ratios were similar at both time points for labelled HIG
      prepared via 2-Me, 2-Im, and NHS-MAG, methods but was significantly lower at 24 h
      for HIG prepared via Sn. The radioactive HPLC profiles of serum at 4 and 24 h
      were similar to that of the radiolabelled injectates. Based on these data we
      conclude that each radiolabelled HIG preparation studied showed increased
      localization in infectious foci although [99Tc]MAG3-HIG showed superior
      radiochemical and biological characteristics under the conditions of this
      investigation.

PMID- 9639303
TI  - Toxicity, mutagenicity, and behavioral effects of beta-CIT, a ligand for dopamine
      transporter exploration by SPECT.
AB  - The cocaine analog beta-CIT is one of the most used compounds for SPET
      examination of the dopamine transporter in drug abuse and Parkinson's disease.
      However, the toxicity of this agent has not yet been studied. We report here
      acute toxicity, mutagenicity, and effect on locomotor activity of beta-CIT. Acute
      toxicity experiments were performed in mice and rats. The LD50 values were about
      20 mg and 5 mg for mice and rats, respectively. There was no sex difference. The
      mutagenicity was evaluated using the Ames' test. No mutagenic effect was observed
      for beta-CIT. Effects on locomotor activity were measured in mice using the open
      field test. beta-CIT increased locomotion (+65%) when injected at a dose of 0.312
      mg/kg; the maximal increase (+205%) was observed at a dose of 1.25 mg/kg; at
      higher doses, the effect was decreased slightly. These pharmacological findings
      are in agreement with an inhibitory effect of beta-CIT at the dopamine
      transporter. We conclude that with no mutagenic effects and LD50 more than 6
      orders of magnitude higher than the routinely used doses in PET or SPET, it can
      be assumed that beta-CIT can be safely used as a radioligand in humans.

PMID- 9639304
TI  - Synthesis, estrogen receptor binding, and tissue distribution of a new
      iodovinylestradiol derivative (17alpha,20E)-21-[123I]Iodo-11beta-nitrato-19-norp
      regna-1,3,5 (10),20-tetraene-3,17-diol (E-[123I]NIVE).
AB  - We have synthesized and evaluated E-11beta-nitrato-17alpha-iodovinylestradiol (E
      NIVE; E-3c) and its 123I-labelled form, as a new potential radioligand for
      imaging of estrogen receptor (ER)-positive human breast tumors. E-[123I]NIVE was
      prepared by stereospecific iododestannylation of the E-tri-n-butylstannylvinyl
      precursor (E-2c), obtained from reaction of 11beta-nitrato-estrone (8) with E
      tributylstannylvinyllithium. In competitive binding studies, E-NIVE proved to
      have high binding affinity for both the rat and the human ER (Ki 280-730 pM),
      without significant binding to human sex hormone binding globulin. Distribution
      studies in normal and mammary tumor-bearing rats showed specific ER-mediated
      uptake of E-[123I]NIVE in the estrogen target tissues, i.e., uterus, ovaries,
      pituitary, and hypothalamus, but not in the mammary tumors. Selective retention
      in these target tissues, including tumor tissue, resulted in significant
      increases over time for the target tissue-to-muscle uptake ratios, but not for
      the target tissue-to-fat uptake ratios. The tumor-to-fat uptake ratio even
      appeared constantly below 1. In the primary estrogen target tissues, E-[123I]NIVE
      displayed high specific ER-mediated uptake and retention, which resulted in
      moderate target-to-nontarget tissue uptake ratios. In contrast, in tumor tissue,
      E-[123I]NIVE uptake appeared to be rather low and not ER-specific. As a
      consequence, E-[123I]NIVE appears to be a less favorable radioligand for ER
      imaging in breast cancer than the previously studied stereoisomers of 11beta
      methoxy-17alpha-[123I]iodovinylestradiol (E- and Z-[123I]MIVE; [123I]E- and
      [123I]Z-3b).

PMID- 9639305
TI  - Monte Carlo-assisted voxel source kernel method (MAVSK) for internal beta
      dosimetry.
AB  - A method is described for the determination of patient-specific organ beta doses
      given a known cumulated internal radioactivity distribution. A voxel source
      kernel for 90Y analogous to the point source function was simulated. Dose to each
      organ of interest could then be estimated by convolving the voxel source kernel
      with the patient's 3-D volume with known radioactivity assigned to each voxel.
      The dose calculation on eight organs took less than 1 min per patient using a Sun
      Sparc10 workstation.

PMID- 9639306
TI  - Comparison of the kit performance of three 99mTc myocardial perfusion agents.

PMID- 9639307
TI  - Physical mapping of chromosomes VII and XV of Saccharomyces cerevisiae at 3.5 kb
      average resolution to allow their complete sequencing.
AB  - The high resolution complete physical maps of chromosomes VII and XV were
      constructed to form the basis for sequencing these chromosomes as part of the
      European systematic sequencing programme of the yeast genome, using a unique
      cosmid library from strain FY1679, and an original top-down mapping strategy
      involving I-Sce I chromosome fragmentation. A total of 138 and 196 cosmid clones
      were used to construct the maps for VII and XV, respectively, forming two unique
      contigs that cover the entirety of chromosomes (1091 kb each), except the
      telomeric repeats. Colinearity of the cosmid inserts with yeast DNA was verified,
      and the physical maps were eventually compared with the independently generated
      genetic maps.

PMID- 9639308
TI  - An extracellular meiosis-promoting factor in Saccharomyces cerevisiae.
AB  - Meiosis and sporulation in the yeast Saccharomyces cerevisiae has been
      classically viewed as an example of unicellular, eukaryotic differentiation that
      occurs in response to nutritional starvation. We present evidence that S.
      cerevisiae produces an extracellular factor(s), called meiosis-promoting factor
      (MEP), that is required, in addition to starvation conditions, for efficient
      meiosis and sporulation. This factor is secreted and accumulates in a cell
      density-dependent fashion such that cells at a low density sporulate poorly under
      conditions in which cells at a high density sporulate efficiently. Conditioned
      medium from sporulating cells at a high density contains a small anionic molecule
      that has cytostatic activity and stimulates sporulation of cells at low density
      under a normal starvation condition. These results indicate that MEP-mediated
      social communication between cells is required for meiosis and sporulation.

PMID- 9639309
TI  - Bicarbonate-mediated social communication stimulates meiosis and sporulation of
      Saccharomyces cerevisiae.
AB  - Meiosis and sporulation in the yeast Saccharomyces cerevisiae requires social
      communication, mediated by an extracellular factor which is secreted from cells
      during sporulation and accumulates in a cell density-dependent manner. We show
      here genetic and biochemical analyses supporting our conclusion that the
      extracellular factor is bicarbonate acting as an alkali to elevate extracellular
      pH. Sporulation defects of mdh1 (mitochondrial malate dehydrogenase) mutants and
      of wild-type cells at low density were rescued extracellularly by addition of
      bicarbonate or other alkaline solutions to raise medium pH. Addition of
      bicarbonate (or alkalization of medium) raised steady-state levels of mRNA in
      respiration-deficient mdh1 mutants and inhibited proliferation of wild-type cells
      at low density. These results indicate that the two conditions (respiration
      competency and high cell density), required for meiosis and sporulation, are
      essential for extracellular accumulation of bicarbonate and resulting
      alkalization of medium.

PMID- 9639310
TI  - The Saccharomyces cerevisiae early secretion mutant tip20 is synthetic lethal
      with mutants in yeast coatomer and the SNARE proteins Sec22p and Ufe1p.
AB  - Tip20p is an 80 kDa cytoplasmic protein bound to the cytoplasmic surface of the
      endoplasmic reticulum (ER) by interaction with the type II integral membrane
      protein Sec20p. Both proteins are required for vesicular transport between the ER
      and Golgi complex. Recently, sec20-1 was found to be defective in retrograde
      transport. A collection of temperature-sensitive tip20 mutants are shown to be
      lethal in combination with ufe1-1, a target SNARE of the ER and ret2-1, yeast
      delta-COP. A subset of tip20 mutants was found to be lethal in combination with
      sec20-1, sec21-1, sec22-3 and sec27-1. Since all pairwise combinations of a tip20
      mutant, sec20-1, and ufe1-1 are lethal, Tip20p and Sec20p might be part of the
      docking complex for Golgi-derived retrograde transport vesicles. Since carboxy
      terminal tip20 truncations are lethal in combination with mutants in three
      coatomer subunits, Tip20p might be involved in binding or uncoating of COPI
      coated retrograde transport vesicles.

PMID- 9639311
TI  - Isolation of the Pichia pastoris PYC1 gene encoding pyruvate carboxylase and
      identification of a suppressor of the pyc phenotype.
AB  - We have cloned and characterized a gene encoding pyruvate carboxylase from the
      methylotrophic yeast Pichia pastoris. Disruption of this gene produced inability
      to grow in minimal medium with glucose as carbon source and ammonium as nitrogen
      source. Growth was possible with aspartate or glutamate as nitrogen source. The
      gene PpPYC1 expressed from its own promoter was able to rescue the phenotype of
      Saccharomyces cerevisiae mutants devoid of pyruvate carboxylase. In a P. pastoris
      strain carrying a disrupted PpPYC1 gene we have isolated spontaneous mutants able
      to grow in non-permissive conditions. In a mutant strain grown in glucose several
      enzymes sensitive to catabolite repression were derepressed. The strain also had
      elevated levels of glutamate dehydrogenase (NAD) both in repressed and
      derepressed conditions.

PMID- 9639312
TI  - Genomic disruption of six budding yeast genes gives one drastic example of
      phenotype strain-dependence.
AB  - Using PCR to construct disruption cassettes, null alleles of six genes have been
      created in Saccharomyces cerevisiae. In a FY1679 background, no defects were
      detected in any of the haploid deletion mutants with respect to growth, gross
      morphology, or mating. A diploid FY1679-derived delta ygl194c/delta ygl194c
      homozygous disruptant displayed reduced sporulation. In contrast to the lack of
      phenotypic consequences of delta yol100w disruptions in the FY1679 background, in
      the CEN.PK2 strain even a heterozygous disruption of the same gene caused
      striking effects, very slow vegetative growth and highly impaired sporulation.
      Tetrad analysis showed YOL100w to be an essential gene in this strain. A copy of
      the YGL194c or the YOL100w wild-type gene borne on a centromeric episomal plasmid
      was introduced into a corresponding disruption mutant strain, and in both cases
      was found to partially complement the defects.

PMID- 9639313
TI  - Identification of a putative histidine kinase two-component phosphorelay gene
      (CaHK1) in Candida albicans.
AB  - We have cloned and analysed the sequence of a putative histidine kinase, two
      component gene (CaHK1) from Candida albicans. This gene encodes a 2471 amino acid
      protein (Cahk1p) with an estimated molecular mass of 281.8 kDa. A homology search
      of Cahk1p with other proteins in the databases showed that Cahk1p exhibits the
      greatest homology at its C-terminus with both the sensor and regulator components
      of prokaryotic and eukaryotic two-component histidine kinases. A further analysis
      of this homology showed that the Cahk1p possessed both sensor and regulator
      domains in the same polypeptide. Also, Cahk1p is likely to be a soluble protein.
      The sensor kinase domain of Cahk1p contains conserved motifs that are
      characteristic of all histidine kinase proteins, including the putative histidine
      which is believed to be autophosphorylated during activation, ATP binding motifs
      and others (F- and N-motifs), with unknown function. The Cahk1p regulator domain
      also contains conserved aspartate and lysine residues and the putative aspartate,
      which is secondarily phosphorylated by the autophosphorylated histidine. Finally,
      according to the codon usage frequency of the CaHK1 gene in comparison with other
      genes from C. albicans, there would appear to be a low level of expression of the
      gene.

PMID- 9639314
TI  - Isolation and characterization of the Candida albicans SEC4 gene.
AB  - The SEC4 gene product is a major component of the protein secretion machinery.
      More specifically, it is believed to play a pivotal role in targeting and fusion
      of secretory vesicles to the plasma membrane. Its recently described implication
      with the Saccharomyces cerevisiae Rho3p, which is required for directing growing
      points during bud formation, has prompted us to investigate the role and function
      of Sec4p in the morphological changes of the yeast pathogen Candida albicans. We
      have therefore cloned the C. albicans SEC4 gene. It encodes a 210 amino acids
      long protein sharing up to 75% homology to the S. cerevisiae homolog, when
      conserved changes are allowed. Its RNA is constitutively expressed in C. albicans
      grown under various physiological conditions. We also show that it can
      functionally complement a S. cerevisiae sec4 thermosensitive mutant.

PMID- 9639315
TI  - Genetic organization and sequence analysis of the hypha-specific cell wall
      protein gene HWP1 of Candida albicans.
AB  - A previously isolated partial cDNA encoding a cell wall protein antigen found on
      hyphal surfaces of the opportunistic fungal pathogen, Candida albicans (Staab et
      al., 1996) was used to clone the complete hyphal wall protein 1 gene (HWP1).
      Hyphal forms of C. albicans invade mucosal surfaces of immunocompromised patients
      such as those with AIDS. HWP1 consisted of an open reading frame predicting an
      acidic protein (pI of 3.37) with a calculated molecular size of 61,122. The
      antigenic domain was located in the N-terminal third of the protein. The
      remainder of the protein contained abundant hydroxy amino acids, and terminated
      with a string of 15 amino acids typical of sequences specifying post
      translational modification with glycosylphosphatidylinositol (6PI). The analyses
      suggested that Hwp1 is a glucan-linked protein with serine/threonine-rich regions
      that are predicted to function in extending a ligand-binding domain into the
      extracellular space.

PMID- 9639317
TI  - Current awareness on yeast.

PMID- 9639316
TI  - The HIS4 gene from the yeast Kluyveromyces lactis.
AB  - The Kluyveromyces lactis HIS4 gene was cloned by complementation of a
      Saccharomyces cerevisiae his4 mutant. Sequence analysis revealed a 2388 bp open
      reading frame encoding a single polypeptide predicted to encompass three distinct
      enzymatic activities (phosphoribosyl-AMP cyclohydrolase, phosphoribosyl-ATP
      pyrophosphohydrolase and histidinol dehydrogenase). This structural organization
      is strikingly similar to that of the His4 proteins from S. cerevisiae and Pichia
      pastoris. Transcript analysis detected a single mRNA species of 2.5 kb.

PMID- 9639318
TI  - Immunolocalization of tumour necrosis factor-alpha (TNF-alpha) in the placental
      bed of normotensive and hypertensive human pregnancies.
AB  - To identify tumour necrosis factor (TNF)-alpha immunopositive cells, third
      trimester human placental bed biopsies were selected from nine normotensive
      control women, 16 severely pre-eclamptic patients and seven patients with pre
      existing hypertension with superimposed pre-eclampsia. In addition, five first
      and early second trimester specimens were included in the study. Immunostaining
      was performed with a mouse IgG1 monoclonal antibody (J1D9) reactive specifically
      with human TNF-alpha (1:300 ascitic fluid), using a biotin-streptavidin
      peroxidase technique. Variable staining of stromal cells was noted in all
      biopsies. Specimens of early pregnancy showed marked immunostaining for TNF-alpha
      on proliferating tips of anchoring villi, invasive interstitial cytotrophoblast
      (but not the multinuclear giant cells), and endovascular trophoblast invading the
      spiral arteries. At term, weak staining was found in trophoblast incorporated
      within spiral artery walls. In biopsies from pre-eclamptic patients, spiral
      arteries without physiological change showed very little staining except in
      atherotic vessels where the infiltrated lipophages often showed intense
      immunolabelling. The marked presence of TNF-alpha in extravillous cytotrophoblast
      of young specimens is suggestive of a role in early invasion. Immunostaining of
      foam cells in non-invaded spiral arteries in pre-eclampsia at or near-term
      indicates a potential role of this cytokine in the development of atherotic
      lesions.

PMID- 9639319
TI  - Decidual spiral artery remodelling begins before cellular interaction with
      cytotrophoblasts.
AB  - Endometrial arteries undergo structural alterations during pregnancy to increase
      blood flow to the intervillous space. It is hypothesized that physiologic change
      in decidual arteries is similar to vascular remodelling seen in other organs.
      Histologic features of spiral arteries in secretory endometrial biopsies were
      compared blindly to decidual arteries from elective abortions. Similar sections
      were stained for trophoblastic and vascular antigens. Spiral arteries in
      endometrium from ectopic (tubal) and intrauterine pregnancies were compared also.
      Evidence of decidual endothelial activation was sought using antibodies to
      vascular cell adhesion molecule (VCAM-1). As expected, decidual arteries were
      significantly different than arteries in secretory endometrium: there was more
      endothelial basophilia, vacuolation, and arterial dilation in early pregnancy.
      Some vessels had disorganized or hypertrophied smooth muscle layers. Similar
      structural alterations were seen in endometrium of ectopic pregnancies, and in
      the decidua parietalis of intrauterine pregnancies. Immunohistochemical studies
      confirmed that these alterations occurred in the absence of cellular interaction
      with extravillous cytotrophoblasts. Independently of trophoblasts, decidual
      endothelial cells expressed VCAM-1. It is concluded that the initial stages of
      physiologic change are characterized by vascular remodelling, which occur in the
      absence of trophoblast invasion of the spiral arteries. Arterial modifications in
      decidua begin as a maternal response to pregnancy.

PMID- 9639320
TI  - Gene expression of nitric oxide synthase in cultured human term placental
      trophoblast during in vitro differentiation.
AB  - The human placental syncytiotrophoblast is derived from differentiating
      cytotrophoblasts and is in contact with maternal blood. This endothelial function
      positions the trophoblast to regulate maternal-fetal exchange and to influence
      circulatory dynamics through paracrine interactions in the placenta. Two isoforms
      of nitric oxide synthase (NOS) are expressed in placenta, and northern analysis,
      reverse transcription-polymerase chain reaction (RT-PCR), and immunocytochemistry
      were used to correlate expression of the type II, inducible NOS (iNOS) and the
      type III, endothelial NOS (eNOS) with state of differentiation in cultured
      trophoblast from term placentae. It was also tested whether cytokines known to
      induce NOS in other cell systems would induce iNOS in human trophoblast. The mRNA
      for eNOS was detected by RT-PCR, but not by Northern analysis, in cultures grown
      for 24 h when cytotrophoblasts were dominant. In contrast, eNOS mRNA was abundant
      in cultures grown for 72 h when syncytiotrophoblast was present.
      Immunocytochemical staining for eNOS protein showed specific fluorescence in a
      few cells in cultures at 24 h, but the vast majority of cells expressed eNOS at
      72 h. The iNOS isoform was expressed neither basally in any trophoblast culture
      nor was this isoform induced in cultures exposed to interleukin-1, tumour
      necrosis factor-alpha, interferon-gamma and lipopolysaccharide. The in vitro
      pattern of trophoblast eNOS expression models the in vivo pattern of eNOS
      expression described for villous trophoblast. The results suggest that eNOS plays
      a role in human trophoblast differentiation and function.

PMID- 9639321
TI  - Increase in expression and activity of thrombomodulin in term human
      syncytiotrophoblast microvilli.
AB  - A comparative study of thrombomodulin (TM), a potent natural anticoagulant, was
      performed in first trimester and term human placentae. Immunoreactive TM was
      observed on fetal vascular endothelium and syncytiotrophoblast at both
      gestational ages. Staining was stronger in term than in early placentae,
      particularly along the microvillous apical membrane of the syncytiotrophoblast.
      Similarly, a higher level of TM mRNA was detected by RT-PCR (P<0.02) and Northern
      blot analysis in extracts of whole term placentae. The localization of TM on
      syncytial microvilli was confirmed by electron microscopy after immunogold
      labelling. When isolated microvilli were compared at both gestational ages; a
      significant 2.3-fold increase in TM protein was observed in term microvilli as
      compared to first trimester microvilli by Western blot analysis (P<0.005) and
      ELISA (P<0.05). This higher level of TM in term microvilli was associated with an
      increase in its ability to activate protein C, from 3.7 +/- 1.2 to 8.7 +/- 4.2
      mOD/min/microg protein +/- s.d. (P<0.01) in first trimester and term microvilli,
      respectively. The modulation of biologically active TM at the syncytial membrane
      exposed to maternal blood according to the length of gestation suggests that TM
      may be involved both in maternal haemostasis within the intervillous spaces, and
      also in the trophoblast differentiation process.

PMID- 9639322
TI  - Demonstration of the expression of CD95 ligand transcript and protein in human
      placenta.
AB  - Tolerance of the fetal allograft enables the human conceptus to implant itself
      into the maternal uterus and survive and grow there. This tolerance phenomenon
      remains largely obscure, notably because it appears to be controlled by multiple
      mechanisms. CD95 ligand (CD95-L), which can trigger death of CD95-positive cells
      by apoptosis, may participate in inducing anti-fetus-sensitized CD95-positive T
      lymphocytes to enter apoptosis. Using immunohistochemistry (first trimester and
      term placentae), FACS assays (term placenta) and RT-PCR assays (term placenta),
      the presence of CD95-L protein and mRNA has been shown in crude placental tissue
      preparations and isolated placental cells. Among the latter, CD95-L expression
      was detected in trophoblastic cells, fetal blood cells (mRNA only) and also the
      Hofbauer macrophages. No CD95-L was detected in fibroblasts or fetal endothelial
      cells. Thus trophoblastic cells, Hofbauer macrophages, and perhaps also fetal
      blood cells could form a sequential barrier blocking maternal activated defence
      cells bearing CD95 molecules.

PMID- 9639323
TI  - Cellular specificity of fibroblastic proMMP-3 downregulation by normal or cancer
      trophoblastic cells.
AB  - It has been shown previously that endometrial fibroblast prometalloproteinase-3
      (proMMP-3) secretion is inhibited by normal cytotrophoblasts as a result of
      paracrine interactions. To investigate the specificity of this downregulation,
      two different types of co-culture were used. First, peritoneal and synovial
      fibroblasts obtained from human tissue biopsies were co-cultured with normal
      cytotrophoblasts. By contrast to what has been observed with endometrial
      fibroblasts, their proMMP-3 secretion increased though their morphology was
      slightly modified. Secondly, the regulation of endometrial proMMP-3 secretion was
      tested in co-cultures with two choriocarcinoma cell lines (JAr and JEG-3 cell
      lines). With tumoral cytotrophoblastic cells, endometrial fibroblasts became
      decidua-like cells and JAr and JEG-3 cell lines grew in syncytium. However, co
      culture of endometrial fibroblasts with JAr and JEG-3 choriocarcinoma cells did
      not decrease proMMP-3 secretion. The present results show that endometrial proMMP
      3 downregulation is tissue specific and does not depend on cell differentiation.
      A cytotrophoblast cell membrane factor which might not be expressed in tumoral
      cells could probably play a role in paracrine relations between epithelial cells
      and surrounding stroma.

PMID- 9639324
TI  - Suppression by beta-mercaptoethanol of the intracellular hormonal dynamics of
      human chorionic gonadotropin-beta subunit (hCG-beta) in BeWo choriocarcinoma
      cells.
AB  - The effects of beta-mercaptoethanol (ME) on the steady-state level of mRNA of the
      human chorionic gonadotropin-beta subunit (hCG-beta) and the intracellular
      hormonal dynamics of the product protein were examined in BeWo cells, a
      choriocarcinoma cell line, using Northern blot analysis and a radioimmunoassay
      (RIA) specific for hCG-beta. ME reduced both medium and intracellular contents of
      hCG-beta in a dose-dependent manner, with its minimum effective dose being 0.01
      per cent. The highest dose used (0.1 per cent) caused more than 90 per cent
      inhibition with both parameters, without affecting the cell number and the cell
      viability as verified by trypan blue exclusion. Significant reductions in both
      the medium and intracellular contents began to occur 6 h after the onset of
      incubation with ME. The ME-induced suppressions were reversible. Northern blot
      analysis showed that ME had no effects on the steady-state level of hCG-beta
      mRNA. When medium and cell lysates collected from ME-free incubations were
      incubated with 0.03 per cent ME, there were significant reductions of
      immunoreactive hCG-beta with both the medium and cell lysates. The magnitude of
      reduction, however, was much greater with the latter (75 per cent) than with the
      former (25 per cent). In contrast, the hCG-beta immunoreactivity of the RIA
      reference preparation was unaffected by incubation with ME. These results
      suggested that the major target(s) of ME action were the intracellularly located
      hCG-beta molecule, presumably its intramolecular disulphide bonds. It must also
      be pointed out that the hCG-beta molecule synthesized and secreted by BeWo cells
      have some structural deviation from the reference standard molecule of normal
      trophoblastic origin to explain the differential susceptibility to ME.

PMID- 9639325
TI  - Decreased placental and umbilical cord glycogen levels associated with meconium
      stained amniotic fluid.
AB  - Most frequently, placental glycogen has been studied as an index of fetal
      nutrition. There are no published studies of placental glycogen as an index of
      fetal stress. In this study of 1573 samples from 71 placentae, glycogen levels in
      the placental disk, fetal membranes and umbilical cord of normal uncomplicated
      pregnancies were compared with those in complicated pregnancies. The complicated
      pregnancies included preterm delivery, hypertensive disorders, inadequate
      prenatal care, substance abuse, maternal fever or infection, obesity, diabetes
      mellitus, premature rupture of membranes, intrauterine growth retardation, sickle
      cell trait, and acute meconium staining of amniotic fluid at delivery. The data
      showed that the only significant differences were in the subgroup complicated by
      meconium-stained amniotic fluid in which the placental disks and umbilical cords
      had significantly lower (P=0.0006) glycogen levels. This finding suggests a
      relatively specific association. It is interesting to speculate that the passage
      of meconium with its vasoconstrictive effect increases utilization of local
      glycogen stores, decreases local glycogen reserves needed for the work of further
      vasoconstriction, and, in the event of subsequent acute stress, impairs vascular
      perfusion of tissues. In this way, meconium could predispose the infant to
      asphyxia.

PMID- 9639326
TI  - Stimulation of prostaglandin production from intact human fetal membranes by
      bacteria and bacterial products.
AB  - The addition of live or sonicated Escherichia coli, or endotoxin from E. coli
      increased the release of prostaglandins (PG) on both sides of intact human fetal
      membranes after 24 h of incubation, indicating that live bacteria were not
      required to activate prostaglandin production. Time-course studies showed that
      the levels of PGE2 and PGF2alpha on the fetal side of the membrane were increased
      6 h after the addition of endotoxin, whereas levels on the maternal side
      increased within 1-2 h. These changes were independent of the side to which the
      endotoxin was added, indicating that a stimulatory factor passes through the
      fetal membranes. This factor is not endotoxin, which did not cross the membranes,
      and further studies are required to identify this endogenous stimulus.
      Prostaglandin metabolite levels were either unaffected or increased by endotoxin,
      indicating that the main effect is at the level of increased prostaglandin
      biosynthesis rather than decreased metabolism.

PMID- 9639327
TI  - Culture of human amniotic cells: a system to study interferon production.
AB  - This study investigated whether primary culture of human amniotic membrane cells
      (PCHAM) could be used as an in vitro model system for the study of interferon
      (IFN) production. PCHAM cells infected with Newcastle disease virus (NDV)
      produced the two antigenic types of IFN, previously shown in a amniotic membrane
      cells (HAM) system. PCHAM IFN was detected as early as 2 h after NDV infection
      and was composed by two antigenically distinct fractions, one neutralized with
      anti-HuIFN beta antibody and another that is not related to IFN beta, -alpha and 
      gamma. These fractions correspond respectively to 80 and 20 per cent of the IFN
      produced 4 h after virus induction, 55 and 45 per cent of the IFN produced from 4
      to 12 h and 67 and 33 per cent of the IFN produced 12 h after virus induction. A
      cDNA library, established from PCHAM with or without NDV infection, was screened
      for IFN alpha and -beta using specific primers. The PCR product, amplified by IFN
      beta primers, was cloned, sequenced and expressed in Escherichia coli M15. The
      sequences of several cloned cDNAs were identical to HuIFN beta gene and the
      antiviral activity of the expressed protein was neutralized only by antiHuIFN
      beta antibody. The other IFN fraction not neutralized by polyclonal antibodies
      anti-IFN beta, -alpha and -gamma is now being studied.

PMID- 9639328
TI  - Mechanisms of chloride transport across the syncytiotrophoblast basal membrane in
      the human placenta.
AB  - Chloride transport mechanisms in isolated plasma membrane vesicles were studied
      to characterize pathways for transcellular transport of chloride. Microvillous
      membrane (MVM) and basal membranes (BM) vesicles were isolated from term
      placentae. Western blot analysis of the anion exchanger isoform 1 (AE1)
      demonstrated that the density of AE1 was 12-fold higher on the MVM compared to
      the BM. At 30 sec, the Cl- uptake in the absence of a potential difference (p.d.)
      was 457.3 +/- 69.7 and 111.0 +/- 29.1 pmol/mg protein in MVM and BM, respectively
      (mean +/- SEM, n=6). Chloride transport pathways were characterized using
      diisothiocyano-2'2-disulphonic stilbene. (DIDS, 0.1 mM) and diphenylamine-2
      carboxylate (DPC, 0.5 mM) in the absence or presence of inside positive membrane
      potentials. Anion exchange (DIDS-sensitive uptake at zero mV) was found in the
      MVM only. Both MVM and BM showed increased chloride uptake in the presence of
      inside positive potentials, suggesting the presence of chloride conductance
      pathways. The chloride uptake with a 25-mV inside positive p.d. could be
      inhibited by both DIDS and DPC in MVM and BM. However greater potentials (50 mV)
      showed no significant inhibition by DIDS or DPC in BM. In conclusion, the anion
      exchanger is unlikely to contribute significantly to chloride fluxes across BM.
      The data also suggest the presence of Cl- conductance pathways in both the MVM
      and BM which are sensitive to both DIDS and DPC.

PMID- 9639330
TI  - Glycine is not formed through the amino transferase reaction in human or rat
      placenta.
AB  - The fetus has a substantial demand for glycine, which is satisfied in part by
      placental formation. The ability to form glycine through the activity of
      alanine:glyoxylate aminotransferase enzyme was measured in placentae from normal
      term human pregnancies and placentae from rats at day 20 of gestation. There was
      no detectable enzyme activity in either human or rat placentae, although activity
      was measured in rat liver. It is concluded that in the placenta glycine is only
      formed from serine through the activity of serine hydroxymethyl transferase
      enzyme, which uses folate as a cofactor, because there are no other known
      metabolic pathways for endogenous glycine production.

PMID- 9639329
TI  - Sodium-independent lysine uptake by the BeWo choriocarcinoma cell line.
AB  - Transport of L-lysine by a cultured placental trophoblast cell line was
      investigated by characterization of L-[3H]lysine uptake. In the mononuclear form
      of the BeWo clone b30 choriocarcinoma cell, at least two sodium-independent
      systems are present. Concentration dependence data were fitted by a two system
      model with Km values (+/- s.e.) of 2 +/- 0.7 and 94 +/- 31 microM and Vmax values
      (+/- s.e.) of 0.7 +/- 0.3 and 25 +/- 6.0 nM/mg DNA/min. A portion of sodium
      independent uptake was inhibited by the sulphydryl modifying reagent N
      ethylmaleimide (NEM). Following NEM treatment, the data were fitted by a single
      system with Km = 10 +/- 2 microM AND Vmax = 5.1 +/- 0.8 nM/mg DNA/min. In the
      absence of sodium, NEM-resistant uptake was sensitively inhibited by leucine
      whereas NEM-sensitive uptake was not inhibited by leucine. It is concluded that
      like placental basal membrane, the mononuclear BeWo cell possesses two sodium
      independent L-lysine transport systems. The high-capacity, NEM-sensitive, leucine
      insensitive system resembles the widespread system y+. The high-affinity, NEM
      resistant, leucine-sensitive system resembles system b(0,+).

PMID- 9639331
TI  - Single case report: late gestational fetal sheep may survive blockage of the
      ductus venosus for 1 week.

PMID- 9639332
TI  - Microelectrode measurements of the potential profile of the pig placenta in
      vitro: evidence for an electrically positive compartment.

PMID- 9639333
TI  - Competition in the NHS internal market: an overview of its effects on hospital
      prices and costs.
AB  - The 1989 reforms of the UK National Health Service (NHS) introduced competition
      in the supply of hospital services. This paper synthesizes both the theory
      underlying the introduction of competition into the NHS, and the limited existing
      evidence on whether competition affects the prices posted by sellers of medical
      services, and the costs of producing these services. The results indicate high
      levels of price variability, widespread disregard for average cost pricing rules
      and some indication that competition had some effect on prices. It appears that
      lower prices may be offered to smaller purchasers, such as General Practice Fund
      Holders (GPFH). This effect of competition on price was mirrored, with a delay,
      in hospital costs.

PMID- 9639334
TI  - Volume responses to Medicare payment reductions with multiple payers: a test of
      the McGuire-Pauly model.
AB  - The effects of changing financial incentives on physician's practice behaviour
      have long been of interest to researchers and policy makers. We test a model of
      physician volume response within the context of multiple payers developed by
      Thomas McGuire and Mark Pauly. A panel data set covering discharges from about
      200 hospitals in the US over 45 months is used to carry out the empirical
      investigation. A fixed-effect model with generalized least squares and
      instrumental variable specifications is used to compute empirical evidence of
      volume responses from eight specialties experiencing varying degrees of Medicare
      payment reductions following the implementation of Omnibus Budget Reconciliation
      Acts of 1989 and 1990. The empirical findings are compared with McGuire and
      Pauly's simulated predictions. We note that in examining physician responses to
      Medicare payment reductions in the context of a multi-payer environment, it
      becomes evident that only fixing one payer's reimbursement policy is at best a
      partial solution to cost containment. We echo observations made by other analysts
      that physician responses to payment changes can be quite complex. Physicians do
      not all respond to payment reduction in the same way.

PMID- 9639335
TI  - Use of economic evaluation guidelines: 2 years' experience in Canada.
AB  - Considerable effort has been expended in recent years in the development of
      methodology guidelines for economic evaluation of pharmaceutical products, driven
      in part by the desire to improve the rigour and quality of economic evaluations
      and to help decision making. Canada was one of the first countries to develop
      such guidelines and to encourage their use. This paper examines the extent to
      which the economic evaluations that were submitted to the Canadian Coordinating
      Office for Health Technology Assessment in the last two years adhered to Canadian
      guidelines. The analytic technique employed by twelve studies as well as the
      comparator used, the perspective taken, the outcome measure selected, the cost
      items that were taken into consideration and the extent of sensitivity analyses
      that were performed are reviewed in this paper. It can be concluded that although
      studies have been of variable quality, the majority of them were well presented,
      complete and transparent, due in part to the guidelines. Except for the
      perspective of the analysis, guidelines were, in many respects, adhered to and
      did not restrict investigators to specific methodologies or specific techniques.
      They were also instrumental in ensuring a minimum set of standards.

PMID- 9639336
TI  - Drug use, drug abuse, and labour market outcomes.
AB  - This paper examines the relationship between illicit drug use and labour market
      success, and in doing so addresses two shortcomings of the previous literature.
      First, unlike many previous analyses, ours accounts for differences in intensity
      of use using clinically based diagnostic measures. Second, while recent studies
      focus only on young adults, we analyze a prime-age (30-45-year-olds) sample as
      well. Our results indicate that these differences are important. Similar to
      previous studies, we find evidence of a positive relationship between drug use
      and income for young workers. However, we also find some evidence of lower
      incomes for young workers reporting daily use of illicit drugs. For prime-age
      men, we find strong evidence that problematic drug use (as indicated by either a
      diagnosis of pathological use or dependence or by daily use) is negatively
      related to income. We also find a negative relationship between problematic use
      and employment among prime-age, but not younger, men.

PMID- 9639337
TI  - Effects of selective contracting on hospital efficiency, costs and accessibility.
AB  - This paper exploits a natural experiment in the state of California, to show that
      pro-competitive healthcare policy may have unintended long-term liabilities
      unless the system as a whole is carefully designed to preserve access to care for
      the poor. California's Medicaid Reform Act of 1982 increased competition among
      hospitals in urban areas, with legislation which allowed direction of patients to
      more efficient providers via selective contracting. This slowed the average rate
      of hospital cost inflation, and saved the state billions of dollars. The
      substantial short-term savings have been documented in empirical research, but
      little attention has been paid to the longer-term effects of the reforms. We find
      that Medicaid contracts were awarded to more efficient hospitals. The
      distributional effects post-reform resulted in efficiency gains for most
      hospitals, but costs escalated for over half of the public hospitals in the
      sample, as their uncompensated care burdens rose. Public hospitals continued to
      fail during the period, leaving over half of California's counties without a
      county hospital by 1990. Because public hospitals provide the vast majority of
      healthcare for the poor in California, there is reason for concern about erosion
      of their access to care as an unintended outcome of pro-competitive reforms.

PMID- 9639338
TI  - Technical efficiency in the clinical management of critically ill patients.
AB  - The purpose of this paper is to obtain empirical measures of performance in the
      management of critical patients treated in intensive care units (ICUs) and to
      evaluate the factors associated with performance, in a two stage approach. In the
      first stage, this paper uses an extended version of Data Envelopment Analysis
      (non-discretionary and categorical variables, and weight constraints under
      consideration) to obtain measures of technical efficiency in the treatment of 993
      critical care patients in intensive care units in Catalonia (Spain) in 1991-92.
      The model incorporates accurate individual measures of illness severity from
      Mortality Probability Models (MPM II0) and quality outcome measures in the input
      output set to obtain non-biased efficiency measures. In the second stage, a
      loglinear regression model is applied to test a number of hypothesis about the
      role of different environmental factors--such as ownership, market structure,
      dimension, internal organization, diagnostic, mortality risk, etc.--to explain
      differences in the efficiency scores.

PMID- 9639339
TI  - Comparison of extrinsic and intrinsic neuromodulation in two central pattern
      generator circuits in invertebrates.
AB  - There are many sources of modulatory input to CPGs and other types of neuronal
      circuits. These inputs can change the properties of cells and synapses and
      dramatically alter the production of motor patterns. Sometimes this enables the
      production of motor patterns by the circuit. At other times, the modulation
      allows alternate motor patterns to be produced by a single circuit. Modulatory
      neurones have fast as well as slow actions. In some cases, such as with GPR, the
      two types of effects are due to the release of co-transmitters. In other cases,
      such as with the DSIs, a single substance can act at different receptors to cause
      fast and slow postsynaptic actions. The effect of a neuromodulatory neurone is
      determined by the type of receptor on the target neurone. Thus a single
      modulatory neurone evokes a suite of actions in a circuit and thereby produces a
      co-ordinated output. Extrinsic and intrinsic sources of neuromodulation have
      different sets of constraints acting upon them. For example, extrinsic
      neuromodulation can easily be used for motor pattern selection; a different
      pattern is produced depending upon which modulatory inputs are active. However,
      intrinsic neuromodulation is not well suited to that task. Instead, it is useful
      for self-organizing properties and experience-dependent effects. One clear
      conclusion from this work and other work in the field is that neuromodulation by
      neurones intrinsic and extrinsic to CPGs is not uncommon (Katz, 1995; Katz &
      Frost, 1996). It is part of the normal process of motor pattern generation. As
      such, it needs to be considered when discussing mechanisms for neuronal circuit
      actions.

PMID- 9639340
TI  - A method for reversible permeabilization of isolated rat ventricular myocytes.
AB  - A method is described that enables the cell membrane of isolated rat ventricular
      myocytes to be permeabilized and resealed while maintaining cell viability.
      Streptolysin O, a cholesterol-binding cytolysin, was used to form pores in the
      surface membrane; subsequent incubation with 5% fetal bovine serum was used to
      reverse this permeabilization. The efficacy of membrane permeabilization and
      resealing was ascertained using a simultaneous double-staining technique using
      propidium iodide, a marker for cells with permeabilized membranes, and
      fluorescein diacetate, a marker for viable cells. This procedure allowed a
      distinction to be made between dead cells, unpermeabilized cells and viable cells
      that had been successfully permeabilized and resealed. The accessibility of the
      cell interior during permeabilization was investigated by including fluorescein
      isothiocyanate (FITC)-labelled dextrans (11, 38 and 148 kDa) and bovine serum
      albumin (67 kDa) in the permeabilization buffer, and localizing the FITC label
      using confocal microscopy following resealing. The confocal images showed that
      these molecules entered the cells and were retained after resealing. Following
      the permeabilization-resealing protocol, cells appeared to have both normal
      morphology and response to electrical stimulation. Thus this appears to be a
      cheap, simple and effective method to introduce relatively large molecules into
      cardiac myocytes.

PMID- 9639341
TI  - Rapid modulation of L-type calcium current by acutely applied oestrogens in
      isolated cardiac myocytes from human, guinea-pig and rat.
AB  - Gender-based differences in cardiovascular mortality may be due to a cardio
      protective effect of oestrogens on the myocardium. However, mRNA expression of
      oestrogen receptors in myocardial tissue of the adult heart has yet to be
      demonstrated. Furthermore, a calcium antagonistic action of 17beta-oestradiol on
      myocardial tissue has been discussed. Therefore, two subjects were investigated
      in atrial myocytes of the human, and ventricular myocytes of guinea-pig and rat
      in this study. (1) Are oestrogen receptors expressed in adult myocardial cells?
      (2) Is there an influence of oestrogens on the L-type calcium current of cardiac
      myocytes? Expression of oestrogen receptors was investigated by reverse
      polymerase chain reaction. L-type calcium current was usually measured by the
      patch-clamp technique in whole-cell recording mode under selective recording
      conditions, i.e. overlapping currents were blocked. One series of experiments was
      performed in perforated patch configuration to avoid internal perfusion. 17beta
      oestradiol inhibited L-type calcium current reversibly in all three species. At
      10(-5) M, the inhibition was 15-20%. This inhibition was independent of the sex
      and the species. A full concentration response curve of 17beta-oestradiol on
      basal L-type current was recorded from female guinea-pig myocytes. The inhibition
      increased from 2% at 10(-7) M to about 30% at 10(-4) M 17beta-oestradiol. The
      values could be fitted by a sum of two sigmoidal functions with log EC50 values
      of -6.5 and -4.9 M and Hill slopes of 2.5 for both. The specificity of the 17beta
      oestradiol action was tested by recording the L-type current in the presence of
      17alpha-oestradiol and oestrone. 17alpha-oestradiol also inhibited the current,
      but with a maximal inhibition of only 17%. The concentration-response curve could
      be fitted by a single sigmoidal function (log EC50 -6-3 M; Hill slope 0.55).
      Oestrone did not influence the current at all. The decrease in L-type current
      after the application of 17beta-oestradiol via a rapid perfusion system developed
      with a time constant of 3-4 s, which was in the same range as that for the
      influence of isoprenaline. The isoprenaline-stimulated L-type current was much
      more susceptible to the inhibition by 17beta-oestradiol, i.e. in pre-stimulated
      cells (1) the inhibitory effect is significantly higher (e.g. at 10(-5) M,
      inhibition was 36.3% compared with 11.2% in untreated cells) and (2) an
      inhibitory effect can be seen with oestradiol concentrations as low as 10(-9) M.
      Although the concentrations needed to gain a calcium antagonistic influence on
      the basal current were much too high to explain a cardio-protective influence of
      oestrogens, the presence of oestrogen receptors in cardiac myocytes of all three
      species, together with the shift in concentration dependence following pre
      stimulation by isoprenaline, suggest that myocytes are a potential target for
      oestrogen.

PMID- 9639342
TI  - Calcium-inhibitable current in cultured embryonic chick cardiac myocytes:
      possibly via a novel chloride channel.
AB  - The role of extracellular Ca2+ (Ca(2+)o) in the modulation of cardiac Cl-
      currents (I(Cl)) such as those activated by cAMP or swelling is uncertain. The
      effects of Ca(2+)o and extracellular cadmium (Cd(2+)o) on Cl- currents in
      cultured chick cardiac myocytes were investigated in Na+- and K+-free internal
      and external solutions using the whole-cell patch-clamp technique. In the absence
      of Na+ and K+ internally and externally, the whole-cell current was predominantly
      I(Cl). In the absence of cAMP, removal of Ca(2+)o (+ 1 mM EGTA) resulted in an
      increase in the current that was suppressed by reduction of Cl(o)- with a
      rightward shift of the zero-current potential towards the CI- reversal potential.
      We designated this current as a Ca2+-inhibitable I(Cl). Addition of 0.5 mM
      Cd(2+)o with or without removal of Ca(2+)o also resulted in a 1.5- to 2.0-fold
      increase in I(Cl) that was attenuated by 1 mM DIDS (4,4'-diisothiocyanatostilbene
      2,2'-disulphonic acid). Under similar conditions, I(Cl) activated by Cd(2+)o (in
      1 mM Ca(2+)o solution) was not further increased by subsequent removal of
      Ca(2+)o, suggesting that addition of Cd(2+)o and removal of Ca(2+)o activated the
      same I(Cl). In contrast, exposure to 1 microM forskolin further enhanced I(Cl) in
      the presence of Cd(2+)o. With 10 microM cAMP in the pipette solution, Ca2+
      inhibitable I(Cl) could be activated in myocytes that do not possess cAMP
      activated Cl- channels, indicating that activation of Ca2+-inhibitable I(Cl) does
      not require cAMP. In the presence of cAMP, in cells that display the cAMP
      activated I(Cl), removal of Ca(2+)o resulted in a further increase in I(Cl)
      comparable to the Ca2+-inhibitable I(Cl). The Ca2+-inhibitable I(Cl) was
      minimized when pipette solutions contained 1.5 microM Ca2+. These results suggest
      that removal of Ca(2+)o or application of Cd(2+)o activates a Ca2+-inhibitable
      I(Cl) that is distinct from the cAMP-activated I(Cl).

PMID- 9639343
TI  - Differential effects of hypoxia on the intracellular Ca2+ concentration of
      myocytes isolated from different regions of the rat pulmonary arterial tree.
AB  - Hypoxic pulmonary vasoconstriction (HPV) may be mediated, in part, by an oxygen
      sensing mechanism intrinsic to pulmonary arterial smooth muscle. It has been
      proposed that hypoxia inhibits a K+ conductance, which promotes membrane
      depolarization, subsequent activation of L-type Ca2+ channels and ultimately
      constriction. We have monitored hypoxia-induced changes in the intracellular Ca2+
      concentration ([Ca2+]i) of single myocytes isolated from the rat pulmonary
      arterial tree using microspectrofluorimetry and ratiometric measurement of indo-1
      fluorescence. The basal level of [Ca2+]i was in the range 35-80 nM and cells were
      quiescent at rest exhibiting no spontaneous oscillations in [Ca2+]i. When the
      extracellular K+ concentration ([K+]o) was raised to 20 mM, the [Ca2+]i increased
      from approximately 60 to approximately 100 nM. This increase was abolished by
      nifedipine, demonstrating the presence, and need for activation, of functional
      voltage-gated L-type Ca2+ channels. Hypoxia (PO2 < or = 30 mmHg; throughout) had
      little effect on the resting [Ca2+]i in myocytes isolated from either the main
      intrapulmonary artery, or its primary, secondary or tertiary branches. However,
      upon raising the [Ca2+]i by increasing [K+]o to 20 mM, hypoxia was found to lower
      [Ca2+]i from approximately 110 to approximately 70 nM, in cells isolated from the
      main conduit and primary branches of the intrapulmonary artery. In marked
      contrast, when [Ca2+]i was raised, by increasing [K+]o to 20 mM, in myocytes
      isolated from secondary and tertiary branches of the intrapulmonary artery,
      hypoxia induced a further reversible increase in the [Ca2+]i from approximately
      160 to approximately 240 nM. Neither hypoxia alone nor in combination with 20 mM
      K(+)o induced any increase in the [Ca2+]i in the presence of nifedipine. We
      conclude that hypoxia may modulate [Ca2+]i in rat pulmonary artery myocytes only
      following its elevation by a depolarizing stimulus.

PMID- 9639344
TI  - Changes in contraction, cytosolic Ca2+ and pH during metabolic inhibition and
      upon restoration of mitochondrial respiration in rat ventricular myocytes.
AB  - Exposure of cardiac muscle to metabolic poisons reduces the availability of
      cellular ATP and cardiac dysfunction ensues. In this study rat ventricular
      myocytes were exposed to 2-deoxyglucose, iodoacetate and cyanide to induce
      complete metabolic blockade. Changes in contraction, cytosolic Ca2+ and pH were
      determined during metabolic blockade and following restoration of mitochondrial
      ATP production. Metabolic blockade resulted in a rapid failure of contractions
      and Ca2+ transients, a rise of diastolic Ca2+, a cytosolic acidosis and
      ultimately a rigor contracture. Washing out cyanide during the development of the
      rigor contracture led to a rapid relaxation of the contracture, a fall in
      cytosolic Ca2+ and a rapid, partial reversal of the cytosolic acidosis. The
      partial reversal of the cytosolic acidosis and fall of cytosolic Ca2+ were
      abolished in the presence of oligomycin. This suggests that the rapid partial
      recovery of cytosolic acidosis could result from the rephosphorylation of ADP to
      ATP by the mitochondrial F1,F0-ATPase (a reaction that consumes protons).

PMID- 9639345
TI  - Site of catecholamine modulation of feto-maternal electric potential difference
      in the pig.
AB  - Feto-maternal vascular (PD(F-M)) and amniotic maternal (PD(A-M)) potential
      differences were measured simultaneously on seven occasions in six conscious pigs
      of 100-106 days gestation. Resting values of PD(F-M) and PD(A-M) were not
      significantly different although the range was wide. Fetal intravascular
      injection of 20 microg adrenaline, but not of saline, was associated with a
      prompt reversible change, of equal magnitude, in both PD(F-M) and PD(A-M). In
      some experiments polarity was reversed. Feto-amniotic potential difference did
      not change. There was no change in fetal plasma K+ and Na+ concentrations.
      Because of the simultaneous and equal alterations in PD(F-M) and PD(A-M)
      following adrenaline and the anatomical configuration of the pig conceptus, we
      conclude that the catecholamine modifiable component of PD(F-M) is generated by
      electrogenesis in the pig placenta, probably by its chorionic (trophoblastic)
      cell layer.

PMID- 9639346
TI  - Temperature dependence of mechanical power output in mammalian (rat) skeletal
      muscle.
AB  - Force-velocity data at different temperatures (range, 10-35 degrees C) from
      intact fibre bundles are analysed to determine the temperature dependence of the
      maximal mechanical power output of fast and slow rat muscles. At 35 degrees C,
      the maximal mechanical power was approximately 250 kW m(-3) (=250 microW mm(-3))
      in fast (probably an underestimate) and approximately 100 kW m(-3) in slow
      muscle. Within the more physiological temperature range (25-35 degrees C), the
      temperature coefficient (Q10) of maximum power was 2-2.5. In both muscles, the
      maximal power at 10 degrees C was only about 3-5% of that at 35 degrees C, the
      decrease being particularly pronounced at temperatures below 20 degrees C (Q10 of
      5-7).

PMID- 9639347
TI  - Cyclical passive stretch influences the mechanical properties of the inactive cat
      soleus.
AB  - The effects of cyclical, passive manipulation (PM, 30 min day(-1), 5 days week(
      1) for 6 months) mimicking the length excursions observed during stepping on the
      mechanical and associated biochemical properties of the inactive cat soleus
      muscle were determined in five cats. Inactivity was produced via spinal cord
      isolation (SI), i.e. complete spinal cord transections at low thoracic and high
      sacral levels and bilateral dorsal rhizotomy between the transection sites.
      Passive manipulation was administered to one leg of each SI cat. Compared with
      normal controls, SI resulted in approximately 70% decrease in weight, an 80%
      decrease in maximum tetanic tension (Po) and an approximately 100% increase in
      maximum rate of shortening (Vmax) and myosin adenosine triphosphatase (mATPase)
      activity of the soleus. The passive manipulation regime partially ameliorated
      these effects. When compared with the control SI soleus, the SI-PM soleus weight
      and maximum tetanic tension were 12 and 21% higher, respectively, and the Vmax
      and mATPase activity 21 and 12% (p > 0.05) lower, respectively. Thus, inactivity
      resulted in a smaller and faster muscle, whereas passive manipulation for only 30
      min a day tended to maintain these properties closer to normal control values.
      The results suggest a potential therapeutic effect of short bouts of cyclical,
      passive manipulation on otherwise inactive skeletal muscles.

PMID- 9639348
TI  - Electrocholecystogram: a study of the electromechanical activity of the gall
      bladder in a canine model.
AB  - To characterize an 'electrocholecystogram' (EChG) for the normal gall bladder
      (GB) that might act as a standard for the evaluation of pathological
      electrocholecystograms of the diseased GB, ten mongrel dogs (14.4+/-3.2 kg) were
      studied. Under anaesthesia, the abdomen was opened and three silver-silver
      chloride electrodes were sutured to the GB serosa. The GB pressure was measured
      by a perfused catheter introduced through the fundus. The response of the
      myoelectrical activity of the GB to balloon distension was tested and the
      direction of electrical waves was defined by GB myotomies. Pacesetter potentials
      (PPs) were recorded exhibiting the same frequency, amplitude and velocity of
      conduction from the three electrodes of each dog on all test days. Action
      potentials (APs) followed the PPs randomly and were associated with a rise of the
      GB pressure. Balloon distension of the GB caused increased PP and AP frequency.
      The electrical waves showed proximally but not distally to GB myotomy, indicating
      that they propagate proximo-distally towards the cystic duct. To conclude, the GB
      possesses electrical waves which are probably initiated from a 'pacemaker' at the
      GB fundus. A normal EChG could be characterized in the canine model. It is
      suggested that this EChG might show changes in gall bladder diseases and might
      thus act as an investigative tool, provided it can be developed to be performed
      percutaneously.

PMID- 9639349
TI  - Gas handling in the caecum of the horse.
AB  - Electromanometric recordings of caecal pressures were made in chronically
      cannulated ponies. Endoscopy allowed direct observation of the caecal base and
      cupola while recording intracaecal pressures and enabled a functional
      interpretation of caecal pressure profiles. Using gas-tight seals, the caecal gas
      cap baseline pressure (tone) was usually below atmosphere, becoming less negative
      postprandially. Diurnal variations were observed in the amplitude and frequency
      of caecal pressure profiles and the direction of caecal movements, during which
      intra-caecal gas cap pressures briefly became positive. A paraprandial (psychic)
      phase of enhanced caecal motility was observed. Manipulation of the caecal gas
      cap volume, by insufflation of nitrogen gas, demonstrated the capacity of the
      caecal base to regulate gas pressures and to eliminate fermenting gases.

PMID- 9639350
TI  - Daily patterns of secretion of neurohypophysial hormones in man: effect of age.
AB  - The neurohypophysial hormone vasopressin contributes to control of urine output
      and, while urine flow shows a clear daily rhythm, there has been debate as to
      whether this is true of neurohypophysial hormones. A study was performed on
      fifteen adult males, with a mean age of 25 years, over a 24 h period, nine blood
      samples being taken at regular intervals for the determination of
      neurohypophysial hormones and indices of fluid balance. Samples were taken via an
      indwelling cannula so that sleep was undisturbed. A daily variation in the plasma
      concentrations of oxytocin and vasopressin was demonstrated with concentrations
      reaching a nadir in the late afternoon. Concentrations of both hormones peaked at
      02.00 h. Vasopressin concentrations were inversely correlated with packed cell
      volume, indicating that the altered hormone release was affecting fluid
      retention. Consistent with this was the observation that the relationship of
      plasma osmolality to vasopressin depended on the time of day. To determine the
      effect of ageing, a similar study was performed on nine healthy elderly subjects
      with a mean age of 70 years. The nocturnal peak of vasopressin was markedly
      attenuated, while oxytocin release was similar to that in the younger group.
      These observations confirm the existence of a daily rhythm in the plasma
      concentrations of neurohypophysial hormones and indicate that the amplitude of
      the vasopressin change decreases with age.

PMID- 9639351
TI  - The effects of substrate and fluid provision on thermoregulatory,
      cardiorespiratory and metabolic responses to prolonged exercise in a cold
      environment in man.
AB  - During prolonged exercise in a cold environment, fatigue is generally associated
      with a depletion of endogenous glycogen stores. This has lead many authors to
      hypothesize that the carbohydrate (CHO) content of fluids ingested in cool
      environments should be high, yet this hypothesis has not been specifically
      examined. In the present study, six healthy males cycled to exhaustion at
      approximately 80% of their maximum oxygen consumption (V2O,max) with either no
      drink (ND), a 15% CHO-electrolyte drink (15% CHO) or a 2% CHO electrolyte drink
      (2% CHO). Dietary intake and exercise were replicated 2 days prior to each trial.
      Mean (S.D.) ambient temperature was 10.0 (0.3) degrees C with a relative humidity
      of 72 (2) % and an air velocity of approximately 0.7 m s(-1) on all trials.
      Weighted mean skin temperature was calculated, and rectal temperature and heart
      rate were recorded at rest, during exercise and at exhaustion. Venous samples
      were drawn before and during exercise and at exhaustion for determination of
      haemoglobin, haematocrit, blood metabolites and serum electrolytes and
      osmolality. Expired air was collected for calculation of VO2 and respiratory
      exchange ratio which were used to estimate rates of fuel oxidation. Ratings of
      perceived exertion (RPE) were also obtained. Exercise capacity was not different
      (P=0.49) between trials, with median (range) times to exhaustion of 90.6 (66.8
      106.0), 97.7 (60.9-112.0) and 102.0 (77.1-170.7) min for the ND, 15% CHO and 2%
      CHO trials, respectively. The 15% CHO drink significantly (P < 0.05) elevated
      blood glucose concentration and total CHO oxidation compared with the ND trial.
      The 2% CHO drink significantly (P < 0.05) reduced the estimated change in plasma
      volume and resulted in a lower serum osmolality than the other two trials. No
      differences were observed in any thermoregulatory or cardiorespiratory responses
      between trials. These data suggest that maintenance of blood-borne substrate
      and/or plasma volume does not influence exercise capacity in the cold, as is
      commonly reported during this type and intensity of exercise in warmer
      environments.

PMID- 9639352
TI  - Measurement of nitric oxide concentration in human skin in vivo using dermal
      microdialysis.
AB  - Using microdialysis, we measured nitric oxide (NO) levels in healthy human skin,
      in vivo, before and during the local inflammatory response to histamine. Basal
      dialysate NO concentration, assayed using an amperometric technique, was 0.49+/
      0.06 microM (mean+/-S.E.M., 21 probes, 14 subjects). Histamine injection produced
      transient increases in NO concentration within both the weal and flare which was
      blocked by the NO synthase inhibitor, NG-nitro-L-arginine-methyl ester (L-NAME).
      Dialysate NO concentration also increased following transdermal delivery of the
      nitrosovasodilator, glyceryl trinitrate. Thus, using microdialysis, it is
      possible to quantify NO production in human skin in vivo and study its modulation
      during the acute inflammatory response.

PMID- 9639353
TI  - Unequal cleavage in the early Tubifex embryo.
AB  - Unequal cleavage that produces two blastomeres of different size is a cleavage
      pattern that many animals in a variety of phyla, particularly in Spiralia, adopt
      during early development. This cleavage pattern is apparently instrumental for
      asymmetric segregation of developmental potential, but it is also indispensable
      for normal embryogenesis in many animals. Mechanically, unequal cleavage is
      achieved by either simple unequal cytokinesis or by forming a polar lobe at the
      egg's vegetal pole. In the present paper, the mechanisms for unequal cytokinesis
      involved in the first three cleavages in the oligochaete annelid Tubifex are
      reviewed. The three unequal cleavages are all brought about by an asymmetrically
      organized mitotic apparatus (MA). The MA of the first cleavage is monastral in
      that an aster is present at one pole of a bipolar spindle but not at the other.
      This monastra form, which arises as a result of the involvement of a single
      centrosome in the MA assembly, is both necessary and sufficient for unequal first
      cleavage. The egg cortex during the first mitosis is devoid of the ability to
      remodel spindle poles. In contrast to the non-cortical mechanisms for the first
      cleavage, asymmetry in the MA organization at the second and third cleavages
      depends solely on specialized properties of the cell cortex, to which one spindle
      pole is physically connected. A cortical attachment site for the second cleavage
      spindle is generated de novo at the cleavage membrane resulting from the first
      cleavage; it is an actin-based, cell contact-dependent structure. The cortical
      microtubule attachment site for the third cleavage, which functions independently
      of contact with other cells, is not generated at the cleavage membrane resulting
      from the second cleavage, but is located at the animal pole; it may originate
      from the second polar body formation and become functional at the 4-cell stage.

PMID- 9639354
TI  - Dorsal specification in blastoderm at the blastula stage in the goldfish,
      Carassius auratus.
AB  - The teleost dorsoventral axis cannot be morphologically distinguished before
      gastrulation. Previous studies by the current authors have shown that localized
      dorsalizing activity in the yolk cell (YC) induces the dorsal tissues in the
      overlying blastoderm. In order to examine whether or not dorsal blastomeres are
      committed to their dorsal fate before the gastrula stage, a variety of transplant
      operations were performed in goldfish blastoderms at the mid- to late-blastula
      stages. When the blastoderm was cut from the YC, rotated horizontally at 180
      degrees, and recombined with the YC, the blastoderm frequently developed two
      axes, indicating that dorsal blastomeres of the blastula had already acquired the
      ability to differentiate into the organizer in the absence of dorsalizing signals
      from the YC. This result was further confirmed by experiments using ventralized
      embryos in which no dorsal structures formed: the axis formation was frequently
      observed in the normal blastoderm combined with the ventralized YC at the
      blastula stage. However, the axes formed in the absence of dorsal information
      from the YC exhibited a lower dorso-anterior index. Furthermore, the dorsal
      specification was not stably maintained when the dorsal cells were located far
      from the YC. These results suggest that the inductive and permissive influence of
      the YC may be required for the blastoderm to undergo full dorsal differentiation.

PMID- 9639355
TI  - Embigin/basigin subgroup of the immunoglobulin superfamily: different modes of
      expression during mouse embryogenesis and correlated expression with carbohydrate
      antigenic markers.
AB  - Embigin and basigin are highly glycosylated transmembrane glycoproteins with two
      immunoglobulin domains and form a subgroup in the immunoglobulin superfamily.
      Previous studies have demonstrated the functional significance of these
      molecules. In the present study, in situ hybridization analysis of their
      expression was performed during mouse embryogenesis. Embigin was strongly
      expressed in the endoderm during early postimplantation embryogenesis, and in the
      somite stage in the gut and visceral endoderm. Embryonic ectoderm and its
      derivative tissues weakly to moderately expressed this molecule. From day 10 to
      15 of gestation, no embigin signal was detected. Basigin was more broadly
      expressed. During the organogenesis period, basigin was expressed in various
      epithelial tissues, brain ventricles, the spinal cord and dorsal root ganglion.
      The modes of expression of these two proteins throughout the egg cylinder stage
      correlated with the expression of the carbohydrate markers that they carry;
      embigin with Dolichos biflorus agglutinin binding sites and basigin with LeX
      antigen and more closely with fucosyltransferase IV, which forms the antigenic
      epitope. These findings imply that proteins with specific carbohydrate epitopes
      play roles in early postimpantation embryogenesis.

PMID- 9639356
TI  - Initial analysis of the molecular image of pamlin, a sea urchin cell adhesion
      protein, by transmission electron microscopy.
AB  - Pamlin, an important extracellular protein required early for sea urchin
      embryogenesis, is readily isolated from the embryos of Hemicentrotus
      pulcherrimus. A molecular image analysis of pamlin was conducted using immuno
      electron microscopy, rotary shadowing and negative staining technique-applied
      electron microscopy. The electron microscopy showed that a monoclonal antibody to
      the pamlin alpha-subunit bound to a position 13.5 nm from one end of a purified
      255 kDa pamlin molecule, which is a 132 nm long and 6.8 nm wide linear structure.
      The pamlin structure is composed of three subunits, a 47 nm long 52 kDa alpha
      subunit that attaches to one end of a 105 nm long 180 kDa beta-subunit, and a
      15.6 nm diameter globular 23 kDa gamma-subunit that binds to the middle of the
      beta-subunit. The alpha- and beta-subunits together form a 125-140nm linear
      structure. Intermolecular aggregation frequently occurred between the free end of
      two beta-subunits of the alphabetagamma pamlin molecule, leaving the entire alpha
      subunit surface free. Occasionally associations between the ends of alpha
      subunits, or between an alpha-subunit and the middle of a beta-subunit also
      occurred, but no aggregations of pamlin formed through the gamma-subunit. These
      homophilic molecular aggregations of pamlin formed a large supramolecular
      network. In addition, the single pamlin molecule rounded at one end under high
      calcium ion concentration to form a 'loop', suggesting the presence of a calcium
      sensitive region in the molecule.

PMID- 9639357
TI  - Effects of wheat germ agglutinin on tunicate egg activation and fertilization: is
      there a plasma membrane sperm receptor system on Ascidia ceratodes eggs?
AB  - Little work has been carried out on the sperm recognition systems present on the
      egg plasma membrane. Here it is shown that wheat germ agglutinin (WGA) interferes
      with the sperm-interacting system on the plasma membrane of eggs of the ascidian,
      Ascidia ceratodes. The WGA activates the dechorionated egg, indicating that a
      plasma membrane sugar residue can be directly tied to egg activation. Low
      concentrations of this lectin do not activate the eggs, but reduce
      fertilizability. This observation suggests that the WGA binding site might be
      part of a sperm reception-activation complex in the plasma membrane. While WGA
      also affects sperm binding to the chorion, the mechanisms of sperm interaction at
      the plasma membrane and chorion show different sensitivities to lectins, sugars
      and enzymes.

PMID- 9639358
TI  - Induction of metamorphosis in the sand dollar Peronella japonica by thyroid
      hormones.
AB  - The larva of the sand dollar Peronella japonica lacks a mouth and gut, and
      undergoes metamorphosis into a juvenile sand dollar without feeding. In the
      present study, it was found that thyroid hormones accelerate the metamorphosis of
      P. japonica larvae. The contents of thyroid hormones in larvae increased
      gradually during development. Thiourea and potassium perchlorate, inhibitors of
      thyroid hormone synthesis, delayed larval metamorphosis and simultaneously
      repressed an increase in the content of thyroxine in the larval body. These
      results suggest that the P. japonica larva has a system for synthesis of thyroid
      hormones that act as factors for inducing metamorphosis.

PMID- 9639359
TI  - Calcium transients accompany ooplasmic segregation in zebrafish embryos.
AB  - Through the injection of f-aequorin (a calcium-specific luminescent reporter),
      and the use of an imaging photon detector, transient localized elevations of free
      cytosolic calcium in the forming blastodisc (BD) and animal hemisphere cortex
      were visualized that correlated with ooplasmic segregation. The introduction of
      an appropriate concentration of the weak (KD = 1.5 micromol/L) calcium buffer
      5,5'-dibromo-BAPTA results in the dissipation of these calcium domains, and
      inhibits cytoplasmic streaming and the subsequent formation of a BD at the animal
      pole. These inhibitory actions are dependent on the final cytosolic concentration
      of buffer within the egg: > or = 1.3 mmol/L blocks ooplasmic streaming; < 1.3
      mmol/L eggs segregate normally. Injection of 5,5'-dimethyl-BAPTA (KD = 0.15
      micromol/L) to a final concentration of 1.5 mmol/L as a control has no effect on
      ooplasmic streaming. These results suggest that localized domains of elevated
      free cytosolic calcium are essential for ooplasmic segregation in zebrafish.
      Furthermore, a hypothetical model is presented linking these calcium transients
      to the contraction of a cortically located actin microfilament network as a
      possible mechanism providing the driving force for segregation.

PMID- 9639360
TI  - Effects of mesenchyme on epithelial tissue architecture revealed by tissue
      recombination experiments between the submandibular gland and lung of embryonic
      mice.
AB  - Lung epithelium during morphogenesis maintains a sheet structure of polarized
      cells lining a lumen, in which E-cadherin, beta-catenin and tight junctional
      proteins are localized at the cell-cell contact sites. On the other hand, the
      submandibular gland epithelium at early stages of development forms a non
      cavitated mass of cells where E-cadherin/beta-catenin are present on the entire
      cell surfaces and tight junctional proteins are almost absent or weakly
      scattered. In the present study, tissue recombination experiments were performed
      between the two organs to explore roles of mesenchyme in the architectural
      development of the epithelium. Homotypic recombinants of both submandibular gland
      and lung showed the tissue architecture as observed in the intact organs. In
      contrast, 11-day lung epithelium cultured with 13-day submandibular mesenchyme
      formed multilayers of cells with the lumen being less visible. It was accompanied
      by redistribution of E-cadherin/beta-catenin along the entire cell surfaces and
      by an irregular distribution of tight junctional proteins. A similar
      redistribution of these molecules was observed in 15-day lung epithelium cultured
      with the submandibular mesenchyme, although the epithelial sheet structure lining
      the lumen was formed. On the other hand, the tissue architecture of submandibular
      gland epithelium was little affected by lung mesenchyme, although the epithelium
      was flattened and showed branching morphogenesis.

PMID- 9639361
TI  - Patterns of gene expression in the core of Spemann's organizer and activin
      treated ectoderm in Cynops pyrrhogaster.
AB  - The presumptive pharyngeal endoderm region of the Cynops early gastrula induces
      head or trunk-tail structures in sandwich culture. Activin-treated ectoderm can
      mimic this phenomenon at least at the histological level. The patterns of
      expression of organizer-specific genes were examined to compare these two
      inductive materials at the molecular level. A chordin cDNA clone from Cynops
      pyrrhogaster (Cychd) was isolated by reverse transcription-polymerase chain
      reaction (RT-PCR). Cychd mRNA was first detected in the presumptive pharyngeal
      endoderm and prechordal plate regions of stage 11 embryos, and was expressed
      continuously until stage 20. The spatiotemporal expression pattern of Cychd was
      similar to that of Xenopus chordin. The patterns of expression of organizer
      related genes in the pharyngeal endoderm and activin-treated ectoderm were
      compared by RT-PCR analysis. Expression of Cychd in these two materials peaked at
      the time when they can induce head structures in sandwich culture. Expression of
      fork head and goosecoid did not change in the presumptive pharyngeal endoderm
      over this period. Cychd may play a key role in head formation in the Cynops
      embryo.

PMID- 9639363
TI  - Existence of gradient in cell adhesiveness along the developing Xenopus hind limb
      bud, shown by a cellular sorting-out experiment in vitro.
AB  - To examine the possibility of a difference in cell adhesiveness along the
      developing Xenopus hind limb bud axes, single mesenchymal cells from developing
      hind limb buds were cultured, allowing them to form an aggregate in a gyratory
      culture system. By observing the distribution of cells within aggregates, it was
      found that sorting-out occurred between cells from different positions and
      different stages. Cells derived from more distal positions tended to be situated
      interiorly in the aggregates. According to Steinberg's differential adhesion
      hypothesis, these results support the idea that there is a graded difference in
      cell adhesiveness along the proximo-distal axis of the developing limb, with
      adhesiveness increasing distally. Although similar sorting-out was observed
      between anterior and posterior cell populations, it could not be determined which
      cell populations were definitely more cohesive. These properties may be
      correlated with the experimentally demonstrated 'positional value', which should
      be different among cells located at different positions along the axes of the
      developing vertebrate limb bud.

PMID- 9639362
TI  - Sequence and expression of a novel mouse gene PRDC (protein related to DAN and
      cerberus) identified by a gene trap approach.
AB  - Gene trapping in embryonic stem (ES) cells was used to identify a novel gene
      involved in mouse development. In order to screen trapped ES cell lines for the
      presence of developmentally regulated genes, an in vitro differentiation test was
      used. One of the G418 resistant cell lines, in conjunction with the lacZ reporter
      gene, showed differential expression patterns under differentiated and
      undifferentiated conditions. The gene trap insertion in this cell line was germ
      line transmitted and X-gal staining was used to assess the expression pattern of
      lacZ in embryos heterozygous for the trapped allele. The reporter gene's
      expression was detected in commissural neurons in the developing spinal cord,
      suggesting functions for the trapped gene in mouse neural development. Structural
      analysis of the cDNA revealed that this trapped gene, named PRDC (protein related
      to DAN and cerberus), is a novel gene that encodes a putative secretory protein
      consisting of 168 amino acid residues. PRDC gene product shows limited
      similarities to the products of DAN (differential screening-selected gene
      aberrative in neuroblastoma) and cerberus. (DAN is a possible tumor-suppressor
      for neuroblastoma in human. Cerberus can induce an ectopic head in Xenopus
      embryos when ectopically expressed.) These three gene products may form a novel
      family of signaling molecules.

PMID- 9639364
TI  - Hantavirus pulmonary syndrome--Colorado and New Mexico, 1998.
AB  - Hantavirus pulmonary syndrome (HPS) is a severe cardiopulmonary illness resulting
      in death in approximately 45% of cases. The most frequently recognized etiologic
      agent of HPS in North America, Sin Nombre virus (SNV), is transmitted to humans
      from its primary rodent reservoir, Peromyscus maniculatus (deer mouse), by direct
      contact with infected rodents, rodent droppings, or nests or through inhalation
      of aerosolized virus particles from mouse urine and feces. Sporadic cases occur
      throughout the United States and Canada, but the potential for spread from
      rodents to humans in 1998 probably has increased because of increased rodent
      population densities in some regions of the country. This report describes three
      cases of HPS that occurred in the southwestern United States with onsets of
      illness during April 15-28, 1998, and recommends methods to avoid exposure to
      rodents inside and around human dwellings.

PMID- 9639365
TI  - Deaths associated with occupational diving--Alaska, 1990-1997.
AB  - During 1989-1997, the Occupational Safety and Health Administration (OSHA)
      recorded 116 occupational diving fatalities in the United States (OSHA,
      unpublished data, 1998). During 1990-1997, nine persons in Alaska died in work
      related diving incidents (four were investigated by OSHA); only one had training
      beyond a recreational diving certificate, and three lacked any certification. In
      response to concerns about adequate training of occupational divers in Alaska and
      recent public inquiry, CDC's National Institute for Occupational Safety and
      Health (NIOSH) reviewed the nine occupational diving fatalities in Alaska. This
      report describes three of these incidents, summarizes the results of the review,
      and provides recommendations to improve the safety of commercial diving.

PMID- 9639366
TI  - Community exposure to toluene diisocyanate from a polyurethane foam manufacturing
      plant--North Carolina, 1997.
AB  - In August 1996, residents of a community in Randolph County, North Carolina,
      contacted the Agency for Toxic Substances and Disease Registry (ATSDR) because of
      health concerns about possible exposure to chemical emissions from a polyurethane
      manufacturing plant. ATSDR and the North Carolina Department of Environment,
      Health, and Natural Resources (NCDEHNR) conducted ambient air monitoring to
      characterize air contamination near the plant. ATSDR and Randolph County health
      officials also conducted biologic monitoring to determine whether residents were
      being exposed to toluene diisocyanate (TDI) emitted from the plant. This report
      summarizes the results of these investigations, which indicate that residents
      were being exposed to TDI in ambient air surrounding the plant.

PMID- 9639367
TI  - Outbreak of Vibrio parahaemolyticus infections associated with eating raw oysters
      -Pacific Northwest, 1997.
AB  - During July-August 1997, the largest reported outbreak in North America of
      culture-confirmed Vibrio parahaemolyticus infections occurred. Illness in 209
      persons was associated with eating raw oysters harvested from California, Oregon,
      and Washington in the United States and from British Columbia (BC) in Canada; one
      person died. This report summarizes the investigations of the outbreak, which
      suggest that elevated water temperatures may have contributed to increased cases
      of illness and highlights the need for enhanced surveillance for human
      infections.

PMID- 9639368
TI  - Multistate outbreak of Salmonella serotype Agona infections linked to toasted
      oats cereal--United States, April-May, 1998.
AB  - During April-May 1998, a total of 11 states reported an increase in cases of
      Salmonella serotype Agona infections; as of June 8, a total of 209 cases have
      been reported and at least 47 persons have been hospitalized, representing an
      eightfold increase over the median number of cases reported in those states
      during 1993-1997. The states reporting increases were Illinois (49 cases),
      Indiana (30), Ohio (29), New York (24), Missouri (22), Pennsylvania (20),
      Michigan (15), Iowa (eight), Wisconsin (six), Kansas (four), and West Virginia
      (two). This report summarizes the outbreak investigation by local, state, and
      federal public health officials, which implicated Millville brand plain Toasted
      Oats cereal manufactured by Malt-O-Meal, Inc. as the cause of illness.

PMID- 9639369
TI  - Measles, mumps, and rubella--vaccine use and strategies for elimination of
      measles, rubella, and congenital rubella syndrome and control of mumps:
      recommendations of the Advisory Committee on Immunization Practices (ACIP).
AB  - These revised recommendations of the Advisory Committee on Immunization Practices
      (ACIP) on measles, mumps, and rubella prevention supersede recommendations
      published in 1989 and 1990. This statement summarizes the goals and current
      strategies for measles, rubella, and congenital rubella syndrome (CRS)
      elimination and for mumps reduction in the United States. Changes from previous
      recommendations include: Emphasis on the use of combined MMR vaccine for most
      indications; A change in the recommended age for routine vaccination to 12-15
      months for the first dose of MMR, and to 4-6 years for the second dose of MMR; A
      recommendation that all states take immediate steps to implement a two dose MMR
      requirement for school entry and any additional measures needed to ensure that
      all school-aged children are vaccinated with two doses of MMR by 2001; A
      clarification of the role of serologic screening to determine immunity; A change
      in the criteria for determining acceptable evidence of rubella immunity; A
      recommendation that all persons who work in health-care facilities have
      acceptable evidence of measles and rubella immunity; Changes in the recommended
      interval between administration of immune globulin and measles vaccination; and
      Updated information on adverse events and contraindications, particularly for
      persons with severe HIV infection, persons with a history of egg allergy or
      gelatin allergy, persons with a history of thrombocytopenia, and persons
      receiving steroid therapy.

PMID- 9639370
TI  - FDA Panel report: January 1998.

PMID- 9639371
TI  - Load-dependent myocyte dysfunction.

PMID- 9639372
TI  - Intracoronary infusion of reduced glutathione improves endothelial vasomotor
      response to acetylcholine in human coronary circulation.
AB  - BACKGROUND: Oxygen free radicals have been shown to cause endothelial vasomotor
      dysfunction. This study examined the effect of reduced glutathione (GSH), an
      antioxidant, on human coronary circulation. METHODS AND RESULTS: Responses of
      epicardial diameter and blood flow of the left anterior descending coronary
      artery to intracoronary infusion of acetylcholine (ACh, 50 microg/min) were
      measured by quantitative coronary angiography and Doppler flow-wire technique,
      respectively, before and during combined intracoronary infusion of GSH (50
      mg/min) or saline in 26 subjects with no significant coronary stenosis. GSH
      infusion suppressed the constrictor response of epicardial diameter to ACh and
      enhanced the increase in blood flow response to ACh. Furthermore, GSH potentiated
      the coronary dilator effect of nitroglycerin. A beneficial effect of GSH on the
      epicardial diameter response to ACh was observed in a subgroup of subjects with >
      or = 1 coronary risk factors but not in a subgroup without risk factors. Saline
      infusion did not have any effects. CONCLUSIONS: The results indicate that GSH
      improved coronary endothelial vasomotor function, particularly in subjects with
      coronary risk factors, and it potentiated the vasodilator effect of nitroglycerin
      in human coronary arteries.

PMID- 9639373
TI  - Angiographic assessment of myocardial reperfusion in patients treated with
      primary angioplasty for acute myocardial infarction: myocardial blush grade.
      Zwolle Myocardial Infarction Study Group.
AB  - BACKGROUND: The primary objective of reperfusion therapies for acute myocardial
      infarction is not only restoration of blood flow in the epicardial coronary
      artery but also complete and sustained reperfusion of the infarcted part of the
      myocardium. METHODS AND RESULTS: We studied 777 patients who underwent primary
      coronary angioplasty during a 6-year period and investigated the value of
      angiographic evidence of myocardial reperfusion (myocardial blush grade) in
      relation to the extent of ST-segment elevation resolution, enzymatic infarct
      size, left ventricular function, and long-term mortality. The myocardial blush
      immediately after the angioplasty procedure was graded by two experienced
      investigators, who were otherwise blinded to all clinical data: 0, no myocardial
      blush; 1, minimal myocardial blush; 2, moderate myocardial blush; and 3, normal
      myocardial blush. The myocardial blush was related to the extent of the early ST
      segment elevation resolution on the 12-lead ECG. Patients with blush grades 3, 2,
      and 0/1 had enzymatic infarct sizes of 757, 1143, and 1623 (P<0.0001),
      respectively, and ejection fractions of 50%, 46%, and 39%, respectively
      (P<0.0001). After a mean+/-SD follow-up of 1.9+/-1.7 years, mortality rates of
      patients with myocardial blush grades 3, 2, and 0/1 were 3%, 6%, and 23%
      (P<0.0001), respectively. Multivariate analysis showed that the myocardial blush
      grade was a predictor of long-term mortality, independent of Killip class,
      Thrombolysis In Myocardial Infarction grade flow, left ventricular ejection
      fraction (LVEF), and other clinical variables. CONCLUSIONS: In patients after
      reperfusion therapy, the myocardial blush grade as seen on the coronary angiogram
      can be used to describe the effectiveness of myocardial reperfusion and is an
      independent predictor of long-term mortality.

PMID- 9639374
TI  - Apoptosis and related proteins in different stages of human atherosclerotic
      plaques.
AB  - BACKGROUND: The transition of a fatty streak into an atherosclerotic plaque is
      characterized by the appearance of focal and diffuse regions of cell death. We
      have investigated the distribution of apoptotic cell death and apoptosis-related
      proteins in early and advanced atherosclerotic lesions. METHODS AND RESULTS:
      Human atherosclerotic plaques were studied by whole-mount carotid endarterectomy
      specimens (n=18). This approach allowed comparison of adaptive intimal
      thickenings, fatty streaks, and advanced atherosclerotic plaques of the same
      patient. The fatty streaks differed from adaptive intimal thickenings by the
      presence of BAX (P<0.01), a proapoptotic protein of the BCL-2 family. Both
      regions were composed mainly of smooth muscle cells (SMCs), and macrophage
      infiltration was low and not different. Apoptosis, as detected by DNA in situ end
      labeling (terminal deoxynucleotidyl transferase end labeling [TUNEL] and in situ
      nick translation) was not present in these regions. Apoptosis of SMCs and
      macrophages, however, was present in advanced atherosclerotic plaques that were
      present mainly in the carotid sinus. A dense infiltration of macrophages (5.8+/
      3% surface area) was present in these advanced atherosclerotic plaques.
      Cytoplasmic remnants of apoptotic SMCs, enclosed by a cage of thickened basal
      lamina, were TUNEL negative and remained present in the plaques as matrix
      vesicles. CONCLUSIONS: We conclude that SMCs within human fatty streaks express
      BAX, which increases the susceptibility of these cells to undergo apoptosis. The
      localization of these susceptible SMCs in the deep layer of the fatty streaks
      could be important in our understanding of the transition of fatty streaks into
      atherosclerotic plaques, which are characterized by regions of cell death. Matrix
      vesicles are BAX-immunoreactive cytoplasmic remnants of fragmented SMCs that can
      calcify and may be considered the graves of SMCs that have died in the plaques.

PMID- 9639375
TI  - Myocyte recovery after mechanical circulatory support in humans with end-stage
      heart failure.
AB  - BACKGROUND: The failing myocardium is characterized by decreased force
      production, slowed relaxation, and depressed responses to beta-adrenergic
      stimulation. In some heart failure patients, heart function is so poor that a
      left ventricular assist device (LVAD) is inserted as a bridge to transplantation.
      In the present research, we investigated whether circulatory support with an LVAD
      influenced the functional properties of myocytes from the failing heart. METHODS
      AND RESULTS: Myocytes were isolated from human explanted failing hearts (HF
      myocytes) and failing hearts with antecedent LVAD support (HF-LVAD-myocytes).
      Studies of myocyte function indicated that the magnitude of contraction was
      greater (9.6+/-0.7% versus 6.9+/-0.5% shortening), the time to peak contraction
      was significantly abbreviated (0.37+/-0.01 versus 0.75+/-0.04 seconds), and the
      time to 50% relaxation was reduced (0.55+/-0.02 versus 1.45+/-0.11 seconds) in
      the HF-LVAD-myocytes compared with the HF-myocytes (P<0.05). The HF-LVAD-myocytes
      had larger contractions than the HF-myocytes at all frequencies of stimulation
      tested. The negative force-frequency relationship of the HF-myocytes was improved
      in HF-LVAD-myocytes but was not reversed. Responses to beta-adrenergic
      stimulation (by isoproterenol) were greater in HF-LVAD-myocytes versus HF
      myocytes. CONCLUSIONS: The results of the study strongly support the idea that
      circulatory support with an LVAD improves myocyte contractile properties and
      increases beta-adrenergic responsiveness.

PMID- 9639376
TI  - Inhibition of neutral endopeptidase causes vasoconstriction of human resistance
      vessels in vivo.
AB  - BACKGROUND: Neutral endopeptidase (NEP) degrades vasoactive peptides, including
      the natriuretic peptides, angiotensin II, and endothelin-1. Systemic inhibition
      of NEP does not consistently lower blood pressure, even though it increases
      natriuretic peptide concentrations and causes natriuresis and diuresis. We
      therefore investigated the direct effects of local inhibition of NEP on forearm
      resistance vessel tone. METHODS AND RESULTS: Four separate studies were
      performed, each with 90-minute drug infusions. In the first study, 10 healthy
      subjects received a brachial artery infusion of the NEP inhibitor candoxatrilat
      (125 nmol/min), which caused a slowly progressive forearm vasoconstriction (12+/
      2%; P=0.001). In a second two-phase study, 6 healthy subjects received, 4 hours
      after enalapril (20 mg) or placebo, an intra-arterial infusion of the NEP
      inhibitor thiorphan (30 nmol/min). Thiorphan caused similar degrees of local
      forearm vasoconstriction (P=0.6) after pretreatment with both placebo (13+/-1%,
      P=0.006) and enalapril (17+/-6%, P=0.05). In a third three-phase study, 8 healthy
      subjects received intra-arterial thiorphan (30 nmol/min), the endothelin ETA
      antagonist BQ-123 (100 nmol/min), and both combined. Thiorphan caused local
      forearm vasoconstriction (13+/-1%, P=0.0001); BQ-123 caused local vasodilatation
      (33+/-3%, P=0.0001). Combined thiorphan and BQ-123 caused vasodilatation (32+/
      1%, P=0.0001) similar to BQ-123 alone (P=0.98). In a fourth study, 6 hypertensive
      patients (blood pressure >160/100 mm Hg) received intra-arterial thiorphan (30
      nmol/min). Thiorphan caused a slowly progressive forearm vasoconstriction (10+/
      2%, P=0.0001). CONCLUSIONS: Inhibition of local NEP causes vasoconstriction in
      forearm resistance vessels of both healthy volunteers and patients with
      hypertension. The lack of effect of ACE inhibition on the vasoconstriction
      produced by thiorphan and its absence during concomitant ETA receptor blockade
      suggest that it is mediated by endothelin-1 and not angiotensin II. These
      findings may help to explain the failure of systemic NEP inhibition to lower
      blood pressure.

PMID- 9639377
TI  - Tachycardia-induced change of atrial refractory period in humans: rate dependency
      and effects of antiarrhythmic drugs.
AB  - BACKGROUND: Atrial fibrillation (AF) has been shown to shorten the atrial
      effective refractory period (ERP) and make the atrium more vulnerable to AF. This
      study investigated the effect of atrial rate and antiarrhythmic drugs on ERP
      shortening induced by tachycardia. METHODS AND RESULTS: Seventy adult patients
      without structural heart disease were included. For the first part of the study,
      right atrial ERP was measured with a drive cycle length of 500 ms before and
      after 10 minutes of rapid atrial pacing using five pacing cycle lengths (450,
      400, 350, 300, and 250 ms) in 10 patients. For the second part of the study, the
      remaining 60 patients were included to study the effects of antiarrhythmic drugs
      on changes in atrial ERP induced by AF. Atrial ERP was measured with a drive
      cycle of 500 ms before and after an episode of pacing-induced AF. After the
      patients were randomized to receive one of six antiarrhythmic drugs
      (procainamide, propafenone, propranolol, dl-sotalol, amiodarone, and verapamil),
      atrial ERP was measured before and after another episode of pacing-induced AF. In
      the first part of the study, atrial ERP shortened significantly after 10 minutes
      of rapid atrial pacing, and the degree of shortening was correlated with pacing
      cycle length. The second part of the study showed that atrial ERP shortened after
      conversion of AF (172+/-15 versus 202+/-14 ms, P<0.0001) and that ERP shortening
      was attenuated after verapamil infusion (-4.6+/-1.2% versus -15.1+/-3.4%,
      P<0.001) but was unchanged after infusion of the other antiarrhythmic drugs.
      Furthermore, all of these antiarrhythmic drugs could decrease the incidence and
      duration of secondary AF. CONCLUSIONS: The atrial ERP shortening induced by
      tachycardia was a rate-dependent response. Verapamil, but not other
      antiarrhythmic drugs, could markedly attenuate this effect. However, verapamil
      and the other drugs could decrease the incidence and duration of secondary AF.

PMID- 9639378
TI  - Inducible nitric oxide synthase expression in smooth muscle cells and macrophages
      of human transplant coronary artery disease.
AB  - BACKGROUND: The inducible isoform of the nitric oxide synthase (iNOS) produces
      large amounts of nitric oxide in response to cytokine stimulation. Previous
      investigations have demonstrated iNOS expression in the setting of acute and
      chronic rejection in experimental cardiac transplant models. The goal of this
      study was to investigate whether iNOS is upregulated in human transplant coronary
      artery disease (TCAD), a major cause of late mortality after cardiac
      transplantation. METHODS AND RESULTS: We studied 15 patients with TCAD and 10
      with normal coronary arteries. In situ hybridization and immunohistochemistry
      were used in tissue sections to localize iNOS mRNA and protein, respectively. The
      presence of peroxynitrite was indirectly assessed by immunostaining with an anti
      nitrotyrosine antibody. Normal coronary arteries had no evidence of iNOS
      expression. In contrast, 30 of 36 coronary artery segments with TCAD (83%) were
      immunostained by the iNOS antibody. The presence of iNOS mRNA was demonstrated in
      these vessels by in situ hybridization. Specific cell markers identified iNOS
      positive cells as neointimal macrophages and smooth muscle cells. Nitrotyrosine
      immunoreactivity colocalized with iNOS expression in arteries with TCAD,
      distributed in macrophages and smooth muscle cells. CONCLUSIONS: iNOS mRNA and
      protein are expressed in human arteries with TCAD, where they are associated with
      extensive nitration of protein tyrosines. These findings indicate that the high
      output nitric oxide pathway and possibly the oxidant peroxynitrite might be
      involved in the process leading to the development of TCAD.

PMID- 9639379
TI  - Role of endogenous endothelin in the development of graft arteriosclerosis in rat
      cardiac allografts: antiproliferative effects of bosentan, a nonselective
      endothelin receptor antagonist.
AB  - BACKGROUND: The purpose of this study was to determine whether endothelin-1 (ET
      1) contributes to the development of graft arteriosclerosis and whether the
      orally active nonpeptide endothelin receptor antagonist bosentan, which blocks
      both ETA and ETB receptors, can protect against this pathologic damage. METHODS
      AND RESULTS: Recipient male Lewis rats were divided into three groups; group 1
      received heterotopic heart transplantations from Lewis donors and groups 2 and 3
      received transplantations from Brown-Norway donors; group 3 recipients also
      received bosentan orally at the dose of 20 mg/kg per day for 120 days. All
      recipients were given cyclosporine and were euthanized at examination 120 days
      after transplantation. Plasma ET-1 levels were significantly higher in group 2
      than in group 1 (6.99+/-0.91 and 4.15+/-.83 pg/mL, respectively). Strong ET-1
      immunoreactivity was seen in both the thickened neointima and the media of the
      coronary arteries in group 2 but not in group 1. The mean ratio of the coronary
      luminal area to the total vascular area in group 2 (19.0+/-11.7%) was
      significantly lower than that in group 1 (34.2+/-9.9%) and was significantly
      increased in group 3 (33.2+/-9.2%). CONCLUSIONS: These results show that local
      upregulation of ET-1, mainly in the thickened neointima and the media of the
      coronary arteries, may play an important role in the pathogenesis of graft
      arteriosclerosis by stimulating ETA receptors, ETB receptors, or both. Orally
      active bosentan might be a useful agent for the clinical prevention of graft
      arteriosclerosis.

PMID- 9639380
TI  - Impaired modulation of sympathetic excitability by nitric oxide after long-term
      administration of organic nitrates in pigs.
AB  - BACKGROUND: Endogenous nitric oxide (NO) reduces sympathetic vasoconstriction by
      attenuating neuronal excitability in the brain stem and inhibition of
      postganglionic neurotransmission. We studied whether this modulation of
      sympathetic circulatory control by NO may be altered during chronic
      administration of NO donor drugs in pigs. METHODS AND RESULTS: Nitrate tolerance
      was induced by oral administration of isosorbide dinitrate (ISDN, 4 mg/kg per day
      for 4 weeks) in eight pigs. Four of them were chronically instrumented for the
      measurement of mean arterial blood pressure and cardiac output in the conscious
      state. ISDN treatment caused hemodynamic tolerance to NO donors and significantly
      increased the hypotensive responses to pharmacologic ganglionic blockade in
      conscious pigs. In general anesthesia, ISDN-treated animals and age-matched
      controls (n=5) had similar baseline renal sympathetic nerve activity and in both
      groups neither inhibition of NO synthases (NOS) nor administration of NO donors
      to the brain stem by intracerebroventricular (i.c.v.) infusions caused
      significant changes in baseline renal sympathetic nerve activity. However,
      whereas sympathoexcitatory responses to glutamate (0.5 mL, 0.1 mol/L, i.c.v.) or
      electrical stimulation of somatic nerve afferents were significantly potentiated
      by central NOS inhibition and attenuated by NO donors in controls, these
      treatments no longer had significant effects in ISDN-treated pigs. Furthermore,
      reflex sympathetic activation in response to intravenous NO donor treatment was
      more pronounced in nitrate tolerant animals, which suggests loss of central
      sympathoinhibitory effects of NO. Subsequent histology on brain stem slices with
      NADPH-diaphorase as NOS marker revealed significant reduction of NOS density in
      ISDN-treated pigs. CONCLUSIONS: Long-term administration of organic nitrates
      reduces the number of NO-producing neurons in the brain stem and causes loss of
      inhibitory effects of NO on sympathetic excitability. This component of tolerance
      to organic nitrates may be important in patients confronted frequently with
      sympathetic activation caused by mental and/or physical stressors.

PMID- 9639382
TI  - Dual-chamber pacing is superior to ventricular pacing: fact or controversy?

PMID- 9639381
TI  - Dual-tracer assessment of coupling between cardiac sympathetic neuronal function
      and downregulation of beta-receptors during development of hypertensive heart
      failure of rats.
AB  - BACKGROUND: Heart failure is associated with activation of the sympathetic
      nervous system and downregulation of beta-receptors. However, the coupling
      between cardiac sympathetic neuronal function and the beta-receptor during the
      development of hypertensive heart failure is not clear. METHODS AND RESULTS: We
      determined cardiac neuronal function and beta-receptors with a dual-tracer method
      of [131I]metaiodobenzylguanidine (MIBG) and 125I-cyanopindolol (ICYP) in Dahl
      salt-sensitive (DS) and salt-resistant (DR) rats. The rats were fed an 8% NaCl
      diet after the age of 6 weeks. Blood pressure was raised to >200 mm Hg at 12
      weeks in DS rats and remained elevated until 18 weeks, but only slightly in DR
      rats. Left ventricular (LV) function of DS rats was preserved at 12 weeks but
      deteriorated at 18 weeks. Despite a 56% reduction of cardiac norepinephrine (NE)
      content at 12 weeks in DS rats, neither MIBG nor ICYP uptake in DS rats was
      different from that of DR rats. At 18 weeks, both MIBG and ICYP uptakes
      decreased, by 52% and 39%, respectively, in association with 71% reduction of
      cardiac NE, in DS rats. MIBG uptake of the LV was homogeneous at 6 weeks but was
      lower in the LV endocardial regions at 18 weeks in DS rats. CONCLUSIONS: The
      present results indicate that cardiac sympathetic neuronal function is relatively
      preserved at the compensated, hypertrophic stage of DS rats but deteriorates in
      association with beta-receptor downregulation at the failing stage. The cardiac
      neuronal dysfunction occurs heterogeneously. A combination of scintigraphic
      portrayal of beta-receptors with MIBG should provide valuable information
      regarding sympathetic nerve signaling in living hearts.

PMID- 9639383
TI  - Images in cardiovascular medicine. Iron deposition in myocardium documented on
      standard computed tomography in cardiac hemochromatosis.

PMID- 9639384
TI  - Images in cardiovascular medicine. Coronary artery ectasia and systolic flow
      cessation in hypertrophic cardiomyopathy.

PMID- 9639385
TI  - Preferential allelic expression can lead to reduced expression of BRCA1 in
      sporadic breast cancers.
AB  - BRCA1 is considered to be a tumor-suppressor gene, yet mutations in this gene are
      uncommon in sporadic breast tumors. We investigated whether mechanisms other than
      DNA mutations that affect the coding region might be involved in breast
      carcinogenesis. Since loss of expression of the BRCA1 gene would lead to lack of
      protein, we evaluated the level of BRCA1 mRNA in 21 normal epithelial specimens
      and in 74 breast carcinomas using quantitative reverse-transcription-polymerase
      chain-reaction (RT-PCR). All normal breast epithelial samples expressed BRCA1
      mRNA. On the other hand, the tumor specimens exhibited approximately 10-fold
      range of levels of BRCA1, with some specimens expressing barely detectable
      amounts of BRCA1 mRNA. The distribution in levels was significantly higher in
      normal breast epithelial cells than in tumor specimens (p = 0.004). Examination
      of the BRCA1 locus indicated that deletion of the BRCA1 gene may account for low
      levels of BRCA1 in a number of specimens. In addition, analysis of samples with
      relatively reduced levels of BRCA1 expression revealed preferential allele
      specific expression in a number of cases, suggesting the presence of regulatory
      mutations. Our data suggest that the BRCA1 gene may be involved in sporadic
      breast carcinogenesis through a reduction in gene expression.

PMID- 9639386
TI  - Quantitative analysis of Th1, Th2 and TGF-beta1 cytokine expression in tumor, TIL
      and PBL of non-small cell lung cancer patients.
AB  - For understanding the local immune response in human non-small cell lung cancer
      (NSCLC), we investigated both Th1 and Th2-type as well as TGF-beta1 cytokine mRNA
      expression in 10 fresh tumor biopsies, the corresponding tumor and short term TIL
      cell lines as well as patient PBMC. A methodology based on a highly sensitive
      quantitative RT-PCR was used. We found that IL-6 mRNA was highly expressed in all
      tumor biopsy samples analyzed (4 LLC, 3 ADC and 3 SCC). IL-10 mRNA was expressed
      in 7 of 10 biopsies whereas IL-4 mRNA expression was moderate. Analysis of type I
      cytokines revealed a low expression level of IL-2 mRNA, while IFNgamma and GM-CSF
      expression was high in the majority of the tumor lesions studied. Quantitatively,
      high amounts of Th2-type cytokine mRNA were detected at the tumor site with IL-6
      as the predominant lymphokine. A high mRNA expression level of the
      immunosuppressive cytokine TGF-beta1 was observed in all NSCLC. To identify the
      cell types responsible for the production of TGF-beta1, IL-6, IL-10 and GM-CSF at
      the tumor site, tumor and TIL cell lines were derived from the corresponding
      biopsies. All the 3 tumor cell lines analysed were found to express high amount
      of TGF-beta1 but not IL-10 mRNA, 2 expressing IL-6 and GM-CSF. Five short term
      TIL cell lines established in the presence of IL-2 expressed high level of IL-10,
      IL-4 and IFNgamma but not IL-2 mRNA. Strikingly, high expression of IL-10 mRNA
      was also observed in all 6 patient PBMC analyzed as compared to controls.
      Together, our results indicate the existence of a local and peripheral Th-2-type
      cytokine pattern in patients bearing NSCLC.

PMID- 9639387
TI  - Perspectives of combined radioimmunotherapy and anti-EGFR antibody therapy for
      the treatment of residual head and neck cancer.
AB  - Rhenium-186 based radioimmunotherapy (RIT) may have potential for the treatment
      of minimal residual disease in patients with squamous cell carcinoma of head and
      neck (HNSCC). In an effort to enhance the efficacy of RIT, we evaluated the
      combination of RIT and anti-epidermal growth factor receptor (EGFR) therapy in
      nude mice bearing established HNSCC s.c. xenografts. For this purpose we used the
      EGFR-blocking monoclonal antibody (MAb) 425. Treatment of HNSCC-bearing mice with
      the combination of a single administration of 200 microCi 186Re-labeled MAb U36
      as well as 1.1 mg unlabeled MAb 425 showed an enhanced efficacy in comparison to
      the single treatments. When 500 microCi 186Re-labeled MAb U36 were administered,
      all tumors eventually regressed completely. The combination of this RIT treatment
      with multiple injections of MAb 425 significantly increased the rate of tumor
      regression. Although RIT with 186Re-labeled MAbs appears to be very efficient on
      HNSCC xenografts, the combination with anti-EGFR MAb 425 may enhance the
      efficacy.

PMID- 9639388
TI  - Expression of SSX genes in human tumors.
AB  - The HOM-MEL-40 antigen which is encoded by the SSX-2 gene was originally detected
      as a tumor antigen recognized by autologous IgG antibodies in a melanoma patient.
      Expression analysis demonstrated that SSX-2 is a member of the recently described
      cancer/testis antigen (CTA) class as it is expressed in a variety of different
      human neoplasms, but not in normal tissues with the exception of testis and a
      weak expression in the thyroid. Further studies demonstrated that SSX-2 belongs
      to a gene family consisting of at least 5 homologous genes. We now report the
      analysis of the expression of all 5 SSX genes in 325 specimens of human neoplasms
      from various histological origins, using reverse transcription polymerase chain
      reaction (RT-PCR). SSX-1, -2, and -4 were found to be expressed in 8%, 15% and
      15%, of the tumors, respectively, while the expression of the SSX-5 gene was rare
      (7/325), and SSX-3 expression was not detected. For defined tumor types,
      expression of at least one of the SSX family members was most frequently observed
      in head and neck cancer (75%), followed by ovarian cancer (50%), malignant
      melanoma (43%), lymphoma (36%), colorectal cancer (27%) and breast cancer (23%),
      while leukemias and the few cases of leiomyosarcomas, seminomas and thyroid
      cancers were found not to express any SSX gene.

PMID- 9639389
TI  - Whole grain food intake and cancer risk.
AB  - The relationship between frequency of consumption of whole grain food and risk of
      selected neoplasms has been analysed using data from an integrated series of case
      control studies conducted in northern Italy between 1983 and 1996. The overall
      dataset included the following incident, histologically confirmed neoplasms: oral
      cavity and pharynx 181, oesophagus 316, stomach 745, colon 828, rectum 498, liver
      428, gallbladder 60, pancreas 362, larynx 242, breast 3,412, endometrium 750,
      ovary 971, prostate 127, bladder 431, kidney 190, thyroid 208, Hodgkin's disease
      80, non-Hodgkin's lymphomas 200, multiple myelomas 120. Controls were 7,990
      patients admitted to hospital for acute, non-neoplastic conditions, unrelated to
      long-term modifications in diet and not likely to have been caused by tobacco or
      alcohol use. Odds ratios (OR) for subsequent scores (never/occasional/frequent)
      of whole grain food consumption were derived after allowance for age, sex,
      education, smoking, alcohol intake and body mass index. High intake of whole
      grain foods consistently reduced risk of neoplasm at all sites, except thyroid.
      The ORs for the highest category of consumption were 0.2-0.3 for upper digestive
      and respiratory tract neoplasms, 0.5 for stomach, colon and gallbladder, 0.7 for
      rectum, 0.6 for liver, 0.8 for pancreas and prostate, 0.9 for breast and
      endometrium, 0.6 for ovary, 0.4 for bladder and kidney, 1.3 for thyroid and
      around 0.5 for lymphomas and myeloma. The tests for trend in risks were
      significant for all neoplasms, except pancreas, endometrium, Hodgkin's disease
      and multiple myeloma. No significant heterogeneity was found across strata of age
      at diagnosis, sex, education, smoking habit, alcohol intake and body mass index.
      Thus, even in the absence of a univocal and satisfactory biological
      interpretation, the consistency of the patterns observed indicate that, in this
      population, higher frequency of whole grain food intake is an indicator of
      reduced risk of several neoplasms.

PMID- 9639390
TI  - Risk factors for endometrial cancer according to familial susceptibility.
AB  - Endometrial cancer (EC) shares some environmental or genetic risk factors with
      colorectal cancer (CRC). It represents a risk factor for CRC. Furthermore, EC is
      the most frequent extracolonic neoplasm in HNPCC (hereditary nonpolyposis
      colorectal cancer) and, in this syndrome, it has the same inheritance pattern as
      CRC. Neoplastic family history and clinical features were evaluated in women with
      EC in a health care district (Pordenone Province) in Northeastern Italy from 1990
      to 1995, to examine the proportion of patients with hereditary cancer and the
      relation with clinical characteristics of EC. We interviewed 215 patients with EC
      (average age 61 years, range 35-88) in relation with some risk factors (age,
      weight, diabetes, menstrual and reproductive pattern, synchronous and
      metachronous neoplasms) and we obtained their family pedigree. Twenty-nine
      patients (13.5%) had a CRC family history, 66 (30.7%) showed an aspecific cancer
      aggregation in their families and more than half (120, 55.8%) had a negative
      cancer family history. Family pedigrees were consistent with a dominant inherited
      cancer pattern in 8 patients (3.7%) belonging to the CRC-related family history
      group. A different pattern of family history distribution emerged in relation
      with age (< 55 vs. > or = 55, p < 0.001) and body mass index (BMI) (< 26 vs. > or
      = 26, p = 0.002). Patients with a CRC pedigree were more numerous in the younger
      group, in the group with lower BMI and in pre-menopausal women.

PMID- 9639391
TI  - Localization of CYP1A1 mRNA in human lung by in situ hybridization: comparison
      with immunohistochemical findings.
AB  - Cytochrome P4501A1 (CYP1A1) is involved in the bioactivation of polycyclic
      aromatic hydrocarbons into their reactive epoxide metabolites. CYP1A1 is
      considered to be important with regard to individual susceptibility to lung
      cancer since phenotypic and genotypic polymorphisms of CYP1A1 have been
      associated with an increased risk of lung cancer in a number of studies. We
      examined here the expression and localization of CYP1A1 mRNA in human lung tissue
      using in situ hybridization with a CYP1A1-specific RNA probe. A centrilobular
      expression of CYP1A1 mRNA was observed in the peripheral lung. The expression was
      intense in bronchiolar epithelium of peripheral lung, especially in terminal
      cuboidal epithelium. Type II alveolar epithelial cells were also intensely
      labelled. Type I alveolar epithelial cells and vascular epithelium exhibited
      binding but the hybridization signals were less intense. Our results are in good
      agreement with our previous work on immunohistochemical localization of CYP1A
      protein, in which we used the 1-7-1 MAb that recognizes both CYP1A1 and CYP1A2.
      In serial sections analyzed with in situ hybridization and immunohistochemistry,
      a similar distribution of CYP1A1 mRNA and CYP1A protein was observed. CYP1A1 mRNA
      is thus expressed in human lungs and the expression is particularly intense in
      the cell types involved in the development of peripheral lung cancers.

PMID- 9639392
TI  - Urinary excretion of 5-(hydroxymethyl) uracil in healthy volunteers: effect of
      active and passive tobacco smoke.
AB  - The urinary excretion of 5-(hydroxymethyl)uracil (5-HMUra), one of the major
      oxidative modifications of thymine, was investigated in 134 healthy volunteers
      living in North Italy. Overnight urine was collected, and a questionnaire was
      completed on smoking habits and exposure to environmental tobacco smoke (ETS). 5
      HMUra was analyzed by GC/MS, following urine purification by HPLC. 5-HMUra
      excretion showed an approximately normal distribution, ranging from 0.08 to 0.84
      (mean 0.44) nmoles/kg/8 hr and from 3.2 to 18.7 (mean 8.5) nmoles/mmoles
      creatinine. 5-HMUra excretion was significantly higher in women than in men and
      in smokers than in non-smokers when results were expressed as the ratio to
      creatinine. Slightly higher levels of 5-HMUra excretion, expressed as
      nmoles/mmoles creatinine, were also found in subjects highly exposed to ETS,
      monitored either as the number of hours of exposure or as the number of smokers
      in the workplace and at home. Our results show that the urinary excretion of 5
      HMUra is higher than that of other oxidized nucleobases, including 8-oxo-7,8
      dihydroguanine, and can be slightly modified by environmental factors such as
      tobacco smoke. These findings suggest that measurement of urinary excretion of 5
      HMUra could be useful as a biomarker of oxidative DNA damage and repair, though
      further research is needed to support these data.

PMID- 9639393
TI  - Adenovirus-mediated p16 gene transfer prevents drug-induced cell death through G1
      arrest in human glioma cells.
AB  - This study examined the effects of full-length p16 gene transfer by recombinant
      adenovirus on cell growth and on sensitivity to CDDP or ACNU chemotherapies. We
      developed a recombinant adenovirus expressing the full-length human p16 gene
      (AxCA-hp16) by the COS-TPC method. AxCA-hp16 was infected into the p16-null human
      glioma cell line, U251MG. AxCA-hp16 infection inhibited proliferation of U251MG
      cells. A proliferation assay employing MTT showed that AxCA-hp16 infection
      induced chemoresistance, preventing CDDP-induced cell death (11- to 15-fold) and
      ACNU-induced cell death (80- to 92-fold). In the absence of AxCA-hp16, cell death
      was induced with CDDP or ACNU at 3 to 5 days after treatment, as demonstrated by
      Trypan-blue exclusion. Flow-cytometric analysis showed that CDDP or ACNU arrested
      cells in the G2 phase on day 1 and that cells re-entered the cycle on day 3.
      However, the cells infected with AxCA-hp16 after CDDP or ACNU treatment showed G1
      arrest on day 5 after re-entering the cycle from G2 arrest on day 3. The cells
      infected with AxCA-hp16 before CDDP or ACNU treatment showed G1 arrest over the 5
      days after the infection. This study demonstrated that G1 arrest induced with p16
      gene expression prevents ACNU- or CDDP-induced cell death. The cell death induced
      by ACNU and CDDP therefore appears to occur in the phase after the G1/S check
      point.

PMID- 9639394
TI  - Changes in glutathione redox cycling and oxidative stress response in the
      malignant progression of NB2 lymphoma cells.
AB  - Differential analysis of closely related Nb2-lymphoma cell lines can be used for
      identification of changes in biochemical properties associated with the malignant
      progression of certain T-cell cancers. As tumors progress, they tend to show
      metabolic alterations such as an increased resistance to oxidative stress, a
      characteristic that may be correlated with changes in intrinsic antioxidant
      levels (e.g., glutathione) and in activities of associated enzymes such as the
      glutathione redox pathway. Whether increases in malignancy of Nb2 cells were
      associated with changes in cellular glutathione levels and activities of
      glutathione-metabolizing enzymes was addressed. To evaluate this relationship, 3
      cell lines, showing increased malignancy, were used: Nb2-U17 (hormone-dependent,
      non-metastatic), Nb2-11 (hormone-dependent, metastatic), Nb2-SFJCD1 (growth
      factor-independent, metastatic). Compared to Nb2-U17 and Nb2-11 cells, the highly
      progressed Nb2-SFJCD1 lymphoma cells maintain low basal glutathione levels.
      However, the Nb2-SFJCD1 cells display an enhanced capacity to produce glutathione
      when challenged with an oxidative stress and show a significantly higher
      resistance to H2O2-induced apoptosis.

PMID- 9639395
TI  - Reversal of multidrug resistance by the staurosporine derivatives CGP 41251 and
      CGP 42700.
AB  - It has been shown previously that the staurosporine derivative CGP 41251, a
      specific inhibitor of protein kinase C (IC50 = 50 nM), exhibits antitumor
      activity and reverses mdr1 mediated multidrug resistance. At present, the
      compound is evaluated as an anticancer drug in clinical phase I trials. We
      compared the effects of CGP 41251 with CGP 42700, another staurosporine
      derivative, which exhibits low protein kinase C inhibiting activity (IC50 = > 100
      microM). We found that in contrast to CGP 41251, CGP 42700 does not show
      antiproliferative activity in HeLa and KB cells in tissue culture (up to a
      concentration of 10 microM). We compared both compounds for their ability to
      reverse mdr1-mediated resistance in KB-C1 and in HeLa-MDR1 cells (transfected
      with the mdr1 gene). CGP 42700 is able to reverse mdr1-mediated resistance to a
      similar extent as CGP 41251. The intracellular accumulation of rhodamine 123 in
      KB-C1 cells following pretreatment with CGP 41251 for 30 min was higher than that
      following treatment with CGP 42700 if determined in medium without serum.
      However, quantitation of rhodamine efflux in an ex vivo assay using human CD8+
      cells in serum showed that CGP 42700 is more effective in inhibiting the efflux
      of rhodamine 123 than CGP 41251. We conclude from our results that (1) CGP 42700
      is more effective in reversal of multidrug resistance in serum than CGP 41251,
      indicating that the compound may be useful for treatment of patients, and (2) CGP
      42700 does not inhibit protein kinase C and cell proliferation and, therefore,
      may be less toxic and elicit less side effects in humans than other
      chemosensitizers.

PMID- 9639396
TI  - Sex- and strain-specific induction of renal tumors by ochratoxin A in rats
      correlates with DNA adduction.
AB  - Ochratoxin A (OTA), a nephrotoxic and carcinogenic mycotoxin, has been implicated
      as an etiologic agent in the Balkan endemic nephropathy (BEN), a chronic disease
      affecting populations in the Balkans. Compared with unaffected individuals,
      patients suffering from BEN and/or urinary tract tumors were more frequently
      found to have a capacity for rapid debrisoquine (DB) metabolism, a metabolic
      reaction related mostly to cytochrome P450 (CYP) 2D in humans. Earlier studies,
      using female DA and Lewis rats phenotyped as poor or extensive DB metabolizers
      respectively, revealed a parallelism between DB-4 hydroxylation and OTA-4
      hydroxylation. To investigate whether genetic polymorphism modifies tumor
      induction, we have compared both OTA-induced renal carcinogenicity and DNA
      adducts in DA and Lewis rats of both sexes. OTA induced renal adenocarcinoma, DA
      male rats being most responsive, while DA females were resistant. Lewis rats
      showed an intermediate renal tumor response. OTA also induced malignant
      transitional cell carcinomas of the bladder in DA male rats only. DNA adducts in
      the kidney, as judged by the nature of spots and prevalence in OTA-treated
      animals, were significantly correlated with renal carcinogenicity of OTA, being
      highest in DA males and lowest in DA females. A parallelism between karyomegalies
      and tumors of the kidney was observed. In conclusion, our results classify OTA as
      a genotoxic carcinogen in rats, with sex-specific response controlled in part by
      drug-metabolizing enzymes that convert OTA into reactive intermediates.

PMID- 9639397
TI  - Radiation-induced apoptosis in human tumor cell lines: adaptive response and
      split-dose effect.
AB  - Irradiation of human ovarian carcinoma cells (OVCAR 3) and myeloma cells (RPMI
      8226) with graded doses of 137Cs-gamma-rays led to a 35-40% increase in time
      dependent apoptosis 72 hr after 6-8 Gy irradiation. Large individual variations
      in sensitivity to radiation-induced apoptosis were noted in human lymphocytes
      obtained from 5 donors. Pretreatment of OVCAR 3 and RPMI 8226 cells with 0.01 Gy
      increased their resistance to apoptosis after subsequent 6 Gy irradiation several
      hours or 48 and 72 hr later. A dose of 4 or 8 Gy given in 2 equal fractions at an
      interval of a few hours produced a low level of apoptosis compared to that
      resulting from a single administration of the same total dose. Adaptive response
      was demonstrated in 2 out of 3 samples of human lymphocytes isolated from
      different donors, and no split-dose effect for apoptosis was noted in 2 other
      donors. In split-dose experiments, there was no correlation between the
      sensitivity of cells to apoptosis and their position in the cell cycle, after the
      first half-dose. No G1 block was observed in irradiated cell lines. Adaptive
      response and split-dose effect were prevented by 3-aminobenzamide and okadaic
      acid which inhibit poly(ADP-ribose)polymerase and protein phosphatase,
      respectively. These results imply a common mechanism for acquired resistance to
      radiation-induced apoptosis in adaptive response and the split-dose effect.

PMID- 9639398
TI  - Activation of MMP-2 by human GCT23 giant cell tumour cells induced by
      osteopontin, bone sialoprotein and GRGDSP peptides is RGD and cell shape change
      dependent.
AB  - We show that osteopontin (OPN), bone sialoprotein (BSP) and GRGDSP peptides, in
      solution, induce activation of metalloproteinase-2 (MMP-2) secreted by human
      GCT23 giant cell tumour cells. Activation of MMP-2 is RGD sequence dependent,
      possibly involves anti-alphaVbeta3 integrins, is preceded by a change from spread
      to rounded cell morphology and is mimicked by the actin depolymerising agent
      cytochalasin B. Cells that had spread on OPN, BSP and GRGDSP substrata failed to
      activate MMP-2, but subsequent addition of soluble GRGDSP induced rounding and
      MMP-2 activation. Activation induced by GRGDSP and cytochalasin B was cell
      mediated, inhibited by EDTA, tissue inhibitor of metalloproteinase-2 (TIMP-2) and
      carboxyl terminal MMP-2 consistent with a role for membrane type (MT)-MMP but did
      not involve urokinase, plasmin or thrombin activity. Activation induced by GRGDSP
      and cytochalasin B, but not cell rounding, was inhibited by herbimycin A,
      cycloheximide and actinomycin D, suggesting a role for tyrosine kinases, protein
      and RNA synthesis, but was not associated with changes in mRNA for MT-MMP-1, MMP
      1, MMP-2, TIMP-1 or TIMP-2. GRGDSP and cytochalasin B enhanced levels of membrane
      associated pro- and active form MMP-1 and MMP-2 but not MT-MMP-1, stimulated cell
      surface MMP-1 staining and induced that of MT-MMP-1, MMP-2 and TIMP-2. This was
      consistent with the possible relocation of constitutive MT-MMP-1 to the cell
      surface as a prerequisite for subsequent cell surface MMP-2/TIMP-2/MT-MMP-1
      complex formation and to the potential induction of conditions favourable for
      reciprocal cell surface MMP-1/MMP-2 activation. Our data provide a novel insight
      into interactions between RGD containing bone matrices, GCT cells and MMPs of
      potential relevance to GCT pathology.

PMID- 9639399
TI  - ras mutation and platinum resistance in human ovarian carcinomas in vitro.
AB  - A panel of 16 human ovarian carcinoma cell lines comprising cisplatin naive as
      well as those with acquired cisplatin resistance was studied to determine if
      there was a relationship between ras status and cisplatin sensitivity. From the
      ras expression studies alongside data produced by direct DNA sequencing, there
      was very little to suggest that ras overexpression or mutation plays a role in
      the cisplatin sensitivity of the panel of human ovarian carcinoma cell lines
      tested. A weak correlation (r2 = 0.53) was found between total Ras protein levels
      and resistance to cisplatin. No relationship was found between Kirsten-Ras
      protein levels and cisplatin sensitivity (r2 = 0.0). Only one ras mutation (codon
      13, Kirsten exon 1, glycine --> aspartate in the HX62 cell line) was observed in
      the cisplatin naive cell lines from the panel which comprised both cisplatin
      sensitive and resistant models. Of interest, however, was that the HX62 cell line
      was the most resistant to cisplatin. No ras mutations were found in those cell
      lines which had repeatedly been exposed, and acquired resistance, to cisplatin.
      The A2780 and CH1 human ovarian carcinoma cell lines were transfected with
      activated, mutant Harvey-ras and, as a result, were shown to display elevated MAP
      kinase phosphorylation in low serum concentration growth medium. No changes in
      cisplatin sensitivity were found following transfection with activated Harvey-ras
      in these 2 human ovarian carcinoma tumor cell models which, importantly, differed
      greatly in their expression of Bcl-2. Therefore, when conducted under similar
      conditions to previously published studies, very little evidence was found to
      support Harvey-ras activation as a factor which can either sensitize or confer
      resistance to cisplatin in human ovarian carcinoma cell lines.

PMID- 9639400
TI  - Enhanced sensitivity to tumor necrosis factor-alpha in doxorubicin-resistant
      tumor cell lines due to down-regulated c-erbB2.
AB  - We have studied the relationship between tumor necrosis factor (TNF)-sensitivity
      and doxorubicin-resistance in our doxorubicin-resistant cell line panel
      consisting of the parental cell line GLC4 plus GLC4-Adr2x and GLC4-Adr350x with
      respective resistance factors of 2 and 350 compared with GLC4. At the highest
      dose of 1000 ng/ml TNF, GLC4 was almost completely resistant to TNF, whereas 37%
      and 68% growth inhibition was observed in GLC4-Adr2x and GLC4-Adr350x,
      respectively. Sensitivity to TNF appeared to correlate inversely with the
      expression and gene copies of topoisomerase IIalpha in these cell lines. The gene
      encoding for c-erbB2 is in the proximity of the topoisomerase IIalpha gene and
      its product is a known cause for TNF-resistance. We found that our doxorubicin
      resistant cell lines with decreased topoisomerase IIalpha gene copies have a
      simultaneous decrease in c-erbB2 gene copies, probably due to linkage between
      these 2 genes. This reduced number of c-erbB2 gene copies resulted in decreased c
      erbB2 expression and subsequently in increased sensitivity to TNF. Additionally,
      we tried to establish some of the mechanisms associated with TNF-resistance in
      GLC4 related to c-erbB2 overexpression. There was no difference in TNF-receptor-1
      expression between the cell lines. Compared with the TNF-sensitive GLC4-Adr350x,
      GLC4 appeared to have a decreased activation of NF-kappaB after exposure to TNF
      that might indicate a reduced TNF-receptor function. In GLC4, increased Bcl-2
      expression was found, a protein described to confer TNF-resistance. Moreover, it
      was demonstrated that combining TNF with the poly-ADP-ribose polymerase (PARP)
      inhibitors 6-aminonicotinamide and 3-aminobenzamide did not affect TNF
      sensitivity in GLC4 and GLC4-Adr350x, excluding a pivotal role of PARP in TNF
      resistance in these cell lines. In conclusion, our data show that doxorubicin
      resistant tumor cell lines with decreased topoisomerase IIalpha gene copies can
      become sensitive to TNF due to loss of c-erbB2 gene copies. We also found that
      several mechanisms associated with c-erbB2 overexpressing contribute to TNF
      resistance in GLC4.

PMID- 9639401
TI  - Enhancement of the anti-tumor immune response using a combination of interferon
      gamma and B7 expression in an experimental mammary carcinoma.
AB  - In recent years, tumor immunotherapy has begun to exploit the emerging knowledge
      of the mechanisms of T cell activation to enhance the immune responses to tumors.
      However, many tumors, despite genetic modification to express co-stimulatory
      molecules or cytokines, are not readily rejected due to their inherently poor
      immunogenicity. In the present study, we tested whether expression of the co
      stimulatory ligand B7-1 and the immunostimulatory cytokines interferon gamma (IFN
      gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF) by a mammary
      carcinoma (SM1) would sufficiently augment its immunogenicity to obtain rejection
      and immunity. Our findings demonstrate that expression of B7, IFN-gamma, or GM
      CSF alone, or co-expression of B7 and GM-CSF did not result in rejection of SM1.
      However, co-expression of B7 and IFN-gamma was sufficient to result in regression
      of SM1 tumors by a CD8+ T cell-dependent mechanism. Rejection of the B7/IFN-gamma
      expressing SM1 tumor resulted in protection from rechallenge not only with the
      unmodified SM1 tumor but with another syngeneic mammary tumor. Our data support
      the idea that although B7 expression alone may not be sufficient for rejection of
      certain tumors, the immune system may be stimulated to mount an effective anti
      tumor immune response by the co-expression of both the co-stimulatory ligand and
      a cytokine.

PMID- 9639402
TI  - Antigen loss variants of a murine renal cell carcinoma: implications for tumor
      vaccination.
AB  - Vaccination with tumour cells genetically modified to support induction of an
      immune response either by production of cytokines or expression of co-stimulatory
      molecules provides a promising therapeutic approach. We have evaluated the
      efficiency of tumour vaccination using RENCA cells, a renal cell carcinoma of the
      BALB/c strain, which were stably transfected with MHC class II, B7.1 or both.
      Tumour growth after vaccination with MHC class II and/or B7.1 transfected RENCA
      cells was extremely variable, with protection close to 100% after vaccination
      with some clones and no effect of vaccination with others. To unravel the
      underlying mechanism, untransfected RENCA cells were cloned, and individual
      clones were tested for immunogenicity; that cloned RENCA cells varied
      considerably in immunogenicity. Whereas all clones displayed comparable growth
      rates in nude mice, some grew very slowly in immunocompetent syngenetic hosts.
      Vaccination with rapidly growing clones was ineffective and, importantly, this
      feature remained unaltered by vaccination with MHC class II and/or B7.1
      transfected clones. Instead, 8 of 10 mice rejected the parental line after
      immunisation with a pool of MHC class II and B7.1 transfected clones. Finally, by
      cloning RENCA cells, we obtained one highly immunogenic clone (P2). Vaccination
      with this clone led to an individual-specific response, which indicates that
      during the cloning procedure a new strongly immunogenic entity must have arisen.
      Taken together, our results indicate that vaccination with MHC II and/or B7.1
      transfected tumour cells induces an efficient immune response, but only if the
      tumour is weakly immunogenic. Since tumours may be composed of clones displaying
      different antigenicities, it is mandatory to use bulk cell populations for
      transfection and vaccination.

PMID- 9639403
TI  - Anti-prostate immunotoxins: cytotoxicity of E4 antibody-Pseudomonas exotoxin
      constructs.
AB  - E4 is a monoclonal antibody (MAb) that reacts with a surface antigen present on
      normal prostate and prostate cancers. Using this antibody, 2 immunotoxins were
      generated, one being a chemical conjugate with a mutant truncated form of
      Pseudomonas exotoxin A (PE), E4-PE35KDEL. The other is a recombinant single chain
      immunotoxin, E4(Fv)-PE38KDEL. The affinity of the conjugated immunotoxin was
      similar to the hybridoma-produced MAb E4, revealing that conjugation did not
      impair the binding ability. The affinity of the recombinant immunotoxin (10 nM)
      was 10-fold lower than that of the MAb, probably reflecting differences of
      bivalent (MAb) vs. monovalent (Fv) binding. Antigen positive prostate, breast and
      colon carcinoma cell lines showed cytotoxic response to the E4 immunotoxins while
      antigen negative cells were not affected. The IC50 value, representing a 50%
      inhibition of cellular protein synthesis, ranged from 0.3 to 20 ng/ml for E4
      PE35KDEL and from 2 to 100 ng/ml for E4(Fv)-PE38KDEL. Therefore, the E4-derived
      immunotoxins may be useful for the treatment of prostate as well as breast and
      colon cancers.

PMID- 9639404
TI  - The Ets-1 and Ets-2 transcription factors activate the promoters for invasion
      associated urokinase and collagenase genes in response to epidermal growth
      factor.
AB  - Urokinase plasminogen activator (uPA) has been associated with invasion and
      metastasis in breast cancer. The expression of uPA and 92 kDa type IV collagenase
      (gelatinase B/MMP-9) is regulated by growth factors, receptor-type tyrosine
      kinases and cytoplasmic oncoproteins. Here, we have identified transcriptional
      requirements for the induction of uPA and 92 kDa type IV collagenase by epidermal
      growth factor (EGF). EGF stimulates the motile and invasive activities
      specifically in the ErbB-2-overexpressing SK-BR-3 cells. Expression of
      extracellular matrix-degrading proteases including type I collagenase/MMP-1, 92
      kDa type IV collagenase/MMP-9, uPA and uPA receptor were induced. EGF also
      transiently stimulated expression of the transcription factors Ets-1 and Ets-2.
      Reporter transfection assays revealed the activation of uPA and MMP-9 collagenase
      promoters by EGF and the requirement of each of the composite Ets and AP-1
      transcription factor binding sites for an EGF response. Most notably,
      transfections with the Ets-1 and Ets-2 expression vectors potentiated uPA and MMP
      9 promoter activation in response to EGF. Mutation of the threonine 75 residue of
      chicken Ets-2 conserved in the Pointed group of the Ets family proteins abrogated
      the ability of Ets-2 to collaborate with EGF. Ets-1 and Ets-2 were highly
      expressed in invasive breast tumor cell lines. Our results suggest that Ets-1 and
      Ets-2 provide the link connecting EGF stimuli with activation of uPA and 92 kDa
      type IV collagenase promoters and may contribute to invasion phenotypes.

PMID- 9639405
TI  - IFNgamma induction of p21WAF1 in prostate cancer cells: role in cell cycle,
      alteration of phenotype and invasive potential.
AB  - Type I and type II interferons (IFNs) are known to exert antitumor effects on a
      variety of tissues and cell types. We have previously shown that the type I IFN
      IFN alpha induces the expression of the cyclin-dependent kinase inhibitor p21WAF1
      and inhibits the cell cycle of the human prostate adenocarcinoma cell line,
      DU145, that carries mutations in the tumor suppressor gene products p53 and pRB.
      We now show that the type II IFN IFN gamma similarly induces the expression of
      p21WAF1 and inhibits the cell cycle of DU145 cells. In addition, we show that
      while both IFNs exert antiproliferative activity, only IFN gamma induced
      phenotypic changes in these cells that accompanied the antiproliferative effect.
      For example, IFN gamma, but not IFN alpha, caused a significant reduction in
      epidermal growth factor receptor expression as well as an increase in the
      adhesion molecules intercellular adhesion molecule-1 and integrin alpha3. These
      phenotypic changes in DU145 cells are suggestive of the acquisition of a non
      tumorigenic state. Consistent with these findings, IFN gamma showed a
      significantly lower invasive ability in in vitro assays using invasion chambers.
      Thus, IFN gamma inhibits both the cell cycle and the metastatic potential of
      DU145 cells independent of the p53 and RB status, and our data describe a
      mechanism for mediating the antitumor capabilities of IFN gamma that bypasses
      tumor suppressor genes like p53.

PMID- 9639406
TI  - Cell cycle-independent induction of apoptosis by the anti-tumor drug Flavopiridol
      in endothelial cells.
AB  - The anti-tumor drug Flavopiridol is a potent inhibitor of cyclin-dependent
      kinases (cdks). As a consequence, Flavopiridol-treated cells arrest in both G1
      and G2, but Flavopiridol has also been shown to be cytotoxic for some tumor cell
      lines. The underlying molecular events are, however, unclear. We now show that
      Flavopiridol induces apoptosis in human umbilical vein endothelial cells
      (HUVECs), as judged by the occurrence of classical apoptotic markers, including
      chromatin condensation, internucleosomal cleavage, DNA fragmentation (TUNEL
      assay), annexin V binding and poly(ADP-ribose) polymerase (PARP)-cleavage. Such
      induction of apoptosis occurs with equal efficiency in both proliferating and
      G0/G1-arrested cells. Because growth-arrested HUVECs lack cdk2 activity and
      contain high levels of the cdk inhibitor p27, our observations suggest that cell
      cycle regulated cdks may not be the only critical target for Flavopiridol-induced
      apoptosis. Surprisingly, A549 lung carcinoma cells were clearly dependent on cell
      proliferation for the induction of cell death, pointing to cell type-related
      differences in the mechanism of Flavopiridol action.

PMID- 9639407
TI  - Antisense inhibition of urokinase: effect on malignancy in a human osteosarcoma
      cell line.
AB  - Expression of urokinase-type plasminogen activator (u-PA) strongly correlates
      with a malignant tumor cell phenotype. In the multistep process of metastasis,
      different cellular functions are influenced by urokinase. The enzyme is known to
      be effective via both proteolytical and signal transduction mechanisms. In the
      present study, the osteosarcoma cell line MNNG/HOS was transfected with a vector
      capable of expressing an antisense transcript, complementary to 1,021 bases of
      the 3' end of u-PA cDNA. This construct was most effective in reducing u-PA
      expression in previous experiments. Stably transfected antisense (as) cell lines
      were characterized and compared with the parental MNNG/HOS. Antisense
      transfection of MNNG/HOS gave the following results: (1) stable incorporation of
      the construct into the genome of as-clones, as detected by Southern blot
      analysis; (2) decreased mRNA level of u-PA, as detected by Northern blot
      analysis; (3) approximately 50% reduced enzyme expression in cell culture medium
      and cell homogenate; and (4) unchanged cellular proliferation activity and u-PAR
      expression. In further functional analysis, as-clones showed (1) significantly
      reduced invasion and motility in modified Transwell chambers (random migration
      and chemotaxis with collagen I as a chemoattractant); (2) significantly reduced
      adhesion on matrices of collagen I and vitronectin; (3) unchanged adhesion
      properties on Matrigel matrix; and (4) reduced metastatic potential to lungs and
      especially liver in chick embryos after i.v. infection into chorioallantoic
      membrane veins. Our data show that in MNNG/HOS urokinase influences cellular
      malignancy by promoting migration and selective adhesion. These specific
      functions were notable in addition to the effects on invasion and basement
      membrane degradation.

PMID- 9639408
TI  - Sensitivity or specificity of reverse transcriptase-polymerase chain reaction
      assays: the real challenge for molecular staging of prostatic carcinomas.

PMID- 9639409
TI  - Detection of illegitimate transcripts of prostate-specific antigen mRNA in blood
      by reverse transcription-polymerase chain reaction.

PMID- 9639410
TI  - Review of alterations of the cyclin-dependent kinase inhibitor INK4 family genes
      p15, p16, p18 and p19 in human leukemia-lymphoma cells.
AB  - The cyclin-dependent kinase inhibitors known as p15, p16, p18 and p19 have been
      suggested as candidates for tumor suppressor genes. The main genetic alterations
      are deletions (bi- or monoallelic) or 5' CpG island methylation of p15 and p16;
      very few cases or cell lines had p18 or p19 deletions or hypermethylation.
      Hypermethylation and homozygous deletions of tumor suppressor genes establish a
      new paradigm of inactivation by lack of expression, in contrast to the previously
      identified tumor suppressors which are predominantly inactivated by point
      mutations followed by loss of the wild-type allele. Here, the literature data on
      alterations of this gene family in more than 4700 primary cases of leukemia or
      lymphoma and some 320 continuous leukemia-lymphoma cell lines are summarized.
      Among hematopoietic malignancies, the highest frequencies of p15del and p16del
      were seen in acute lymphoblastic leukemia (ALL) (>30%) with striking rates in T
      ALL (>50%), but also high rates in B cell precursor (BCP)-ALL (>20%); the rates
      of deletions in chronic lymphoid leukemia (CLL), multiple myeloma, acute and
      chronic myeloid leukemia (AML and CML), and myelodysplastic syndromes (MDS) were
      rather low, only some B cell and T cell lymphomas showed increased frequencies.
      Results are quite different with regard to the second mode of inactivation,
      hypermethylation of the promoter region. Here, p15 is most often inactivated, at
      particularly high frequencies in the disorders lacking any p15/p16 deletions: 40
      80% p15met in AML, MDS and multiple myeloma. Also p15met rates in BCP- and T-ALL
      cases were high (c. 40%). There is controversy concerning the prognostic impact
      of p15 and p16 aberrations with some studies describing a significant correlation
      between inactivation of these genes and poor prognosis, while most others did not
      detect any prognostic relevance, at least in pediatric ALL; there may be a worse
      prognosis for adults with B or T cell lymphomas. Despite the small number of
      cases studied, paired sequential analyses suggested that disease progression is
      associated with loss of p15/p16 activity in a certain percentage of adult
      patients. p15del/p16del and p15met/p16met were also detected in the large panel
      of leukemia-lymphoma cell lines studied. In general, the results in cell lines
      reproduce the data seen in primary cells with the important difference that the
      rates of p15/p16 inactivation are clearly higher in the cultured cells compared
      with the freshly explanted cells. Retrovirus- or electroporation-mediated ectopic
      gene transfer of p16 wild-type into p16-deficient cell lines led to growth
      inhibition, arrest in G1 (without apoptosis) and occasionally to differentiation,
      suggesting that the malignant phenotype of p16-/- cell lines can, at least
      partially, be reversed by restoring p16 gene expression. A striking inverse
      correlation between the absence of p16 (due to deletion) and presence of wild
      type retinoblastoma gene was observed in cell lines confirming a common growth
      suppressor pathway; no comparable relationship of p16 inactivation with p53 was
      detected. Paired analysis of cell lines and corresponding primary cell material
      showed that in all instances tested both populations carried the same gene
      configuration of p15 and p16. Thus, p15del or p16del did not occur during
      establishment of the cell lines or during prolonged culture. It is likely that
      p15 or p16 deletions already acquired in vivo provide a dramatic growth advantage
      for the immortalization process in vitro, thus increasing the success rate for
      cell line establishment which is commonly extremely difficult. In conclusion, the
      present review suggests an involvement of the p15 and p16 tumor suppressor genes
      in leukemo- and lymphomagenesis. Future studies will determine their exact role
      in the development and progression of hematopoietic neoplasms. These genes may
      represent interesting targets for new therapeutic strategies.

PMID- 9639411
TI  - GM-CSF can improve the cytogenetic response obtained with interferon-alpha
      therapy in patients with chronic myelogenous leukemia.
AB  - Patients with chronic myelogenous leukemia (CML) who achieve a major cytogenetic
      remission when treated with interferon-alpha (IFN-A) have a survival advantage
      when compared to patients with no cytogenetic response. We investigated the
      effect of combining granulocyte-macrophage colony-stimulating factor (GM-CSF)
      with IFN-A in the cytogenetic response of patients with minor responses to IFN-A
      alone. CML patients were eligible if they had shown sensitivity to IFN-A as
      determined by achievement of a hematologic or cytogenetic response, but failed to
      achieve or lost a major cytogenetic response after a minimum of 12 months of
      therapy with IFN-A alone. Patients received GM-CSF 30 microg/m2 daily,
      subcutaneously and the dose was escalated to 60 microg/m2 if tolerated. IFN-A was
      continued at the same dose being received by the patient and escalated when
      possible. Fourteen evaluable patients were included, 13 in chronic phase and one
      in accelerated phase. The best response prior to GM-CSF was a transient major
      cytogenetic response in two patients (14%), minor cytogenetic response in nine
      (64%), and complete hematologic response in three (22%). The median time on IFN-A
      prior to the start of GM-CSF was 39 months (range 12-72 months). Four patients
      achieved a significant cytogenetic response, including two complete (14%) and two
      partial (14%) cytogenetic remissions during therapy. One partial cytogenetic
      remission converted to complete shortly after therapy was discontinued. Two other
      patients had a significant reduction in the percentage of Philadelphia chromosome
      positive metaphases. The dose of IFN-A could be escalated in half of the patients
      treated. No toxicity could be attributed to the addition of GM-CSF. We conclude
      that the addition of GM-CSF to the treatment with IFN-A in CML patients who are
      sensitive to IFN-A alone but fail to achieve a major cytogenetic response may be
      beneficial in some patients and should be further investigated.

PMID- 9639412
TI  - A phase I trial of a single high dose of idarubicin combined with high-dose
      cytarabine as induction therapy in relapsed or refractory adult patients with
      acute lymphoblastic leukemia.
AB  - Relapsed or refractory adult acute lymphoblastic leukemia (ALL) carries a grave
      prognosis. The most promising strategy for curing these patients is through re
      induction chemotherapy followed by successful allogeneic transplant. We studied a
      new high-dose induction regimen in order to improve the outcome for these
      patients. Eighteen adult patients with relapsed/refractory ALL were treated on a
      phase I study of high-dose cytarabine combined with a single escalating dose of
      idarubicin. Five patients had primary refractory disease and 13 were treated in
      refractory relapse. Nine patients (50%) had Ph+ ALL. The induction regimen was
      cytarabine 3 g/m2/day intravenously days 1-5 and idarubicin as a single
      intravenous dose on day 3. G-CSF 5 microg/kg subcutaneously every 12 h was
      started on day 7. The initial idarubicin dose was 20 mg/m2 with dose escalations
      of 10 mg m2. Cohorts of three patients were treated at each idarubicin dose
      level. Unacceptable toxicity was encountered at 50 mg/m2 with one death from
      infection and one death from cardiotoxicity in a patient with significant prior
      anthracycline exposure. There were no instances of grade 4 non-hematologic
      toxicity encountered at idarubicin doses of 20 mg/m2, 30 mg/m2, or 40 mg/m2. The
      data suggest a dose-response relationship for increasing doses of idarubicin with
      0/3 complete responses (CR) at 20 mg/m2, 1/3 CR at 30 mg/m2, and 7/12 (58%) CR at
      idarubicin doses > or = 40 mg/m2. We conclude that concomitant administration of
      cytarabine 3 g/m2/day x 5 and high-dose idarubicin at 40 mg/m2 as a single dose
      on day 3 can be administered safely to patients with refractory and relapsed ALL.

PMID- 9639413
TI  - Polycythemia vera treated with pipobroman as single agent: low incidence of
      secondary leukemia in a cohort of patients observed during 20 years (1971-1991).
AB  - The 'gold standard' for the treatment of polycythemia vera (PV) is to date
      undefined. We performed a retrospective analysis to evaluate the outcome of a
      cohort of PV patients treated with pipobroman (PB) at a single institution during
      a period of 20 years (November 1971-October 1991). During this period, a total of
      366 adult PV patients were diagnosed according to Polycythemia Vera Study Group
      (PVSG) criteria. Of these, only 199 (54%) were treated with PB: 92 were males and
      107 females, median age was 63.0 years (range 25.2-87.3 years). Major clinical
      characteristics at onset were as follows: 34 (17%) patients had splenomegaly >3
      cm below costal margin, 70 (35%) had platelets >600,000/mm3, 79 (40%) had white
      blood cells >12,000 mm3; 97 (49%) had hypertension, 83 (42%) had minor
      neurological symptoms (as vertigo, headache, paresthesias), 33 (17%) had pruritus
      and 27 (13%) had thrombotic features. All patients received PB at the dosage of 1
      mg/kg/day until response was achieved (hematocrit value <50% in males and <45% in
      females). Thereafter treatment was given according to toxicity and maintenance of
      response. All patients were phlebotomized before starting treatment (mean number
      of phlebotomies performed: three, range 2-4) and 47 of them received PB when
      hematocrit value was already reduced at response levels: therefore, while all
      patients are evaluable for acute and long-term toxicity, only 152/199 (76.4%)
      patients are evaluable for response to PB. During a median time of 2 months, all
      these 152 patients achieved the response; as maintenance, 128/199 (64.3%)
      patients were managed with PB alone and 71/199 (35.7%) patients received
      phlebotomies occasionally. Sixty-one out of 199 (30.6%) patients developed
      disease-related complications (25 neurological symptoms, 21 thrombotic
      complications, 12 cardiovascular problems, three hepatic failures). Eleven (5.5%)
      patients developed acute myelogenous leukemia (AML) after a median time of
      treatment of 89 months (range 33-188 months), 11 (5.5%) patients developed
      myelofibrosis (median time from treatment 71 months, range 31-182 months) and in
      six (3%) patients cancer occurred (median time from treatment 85 months, range 13
      118 months). The cumulative risk of leukemia in PV was 2% (95% CI: 0-4%) and 6%
      (95% CI: 1-11%) at 5 and 10 years respectively; the cumulative risk of
      myelofibrosis was 2% (95% CI: 1-5%) and 9% (95% CI: 3-15%) at 5 and 10 years,
      respectively. As of May 1996, 33 (16.6%) patients are lost to follow-up, 40
      (20.1%) are dead and 126 (63.3%) are alive with a median overall survival of 191
      months. In conclusion, this retrospective analysis confirms the efficacy and
      safety of PB in PV patients and its low leukemogenic role; prospective studies
      are needed to evaluate the real impact of PB in the treatment of PV.

PMID- 9639414
TI  - Acute lymphoblastic leukemia with maturation--a new entity with clinical
      significance.
AB  - The diagnosis of 'ALL with maturation' (ALLm) is proposed. One hundred and one
      patients with untreated ALL were entered into this study. The diagnosis of ALLm
      was made when more than 20% of all nucleated elements in the bone marrow showed
      maturation beyond prolymphocytes by light microscopic examination. The mature
      appearing leukemic cells showed the same immunophenotype to remaining
      lymphoblasts. The number of ALLm cases was 19 (18.8%). The mean age at
      presentation of ALLm was 29 +/- 18, older than that of 18 +/- 16 of the remaining
      typical ALL (ALLt) (P = 0.015). Remission was induced with daunorubicin,
      vincristine, prednisone and L-asparaginase. Only two of 19 ALLm patients achieved
      CR after 4 weeks induction chemotherapy. In contrast, 57 of 82 (69.5%) ALLt
      patients achieved CR after the same induction chemotherapy. There was no
      significant difference in immunophenotype of ALLm compared with ALLt. Labeling
      index of DNA topoisomerase IIalpha (TopoLI) was studied by immunohistochemistry.
      Initial TopoLI of ALLm (221 +/- 147) was much lower than that of ALLt (609 +/-
      262, P = 0.005). Furthermore, the remaining leukemic cells after chemotherapy
      were not labeled with anti-DNA topoisomerase IIalpha. The P53 protein was
      expressed in nine of 18 ALLm cases (50.0%) and P-glycoprotein was not expressed
      in ALLm cases. Twelve of 19 ALLm cases were studied for carrying bcr/abl fusion
      by karyotyping and/or fluorescent in situ hybridization. Only two cases revealed
      bcr/abl fusion. In conclusion, ALLm is a separate entity of ALL which has a very
      poor clinical course and is independent of other prognostic factors. The
      morphologically mature leukemic cells are in resting GO phase.

PMID- 9639415
TI  - CD34+/CD36- cells from myelodysplasia patients have a limited capacity to
      proliferate but can differentiate in response to Epo and MGF stimulation.
AB  - Myelodysplasia (MDS) is mostly characterized by a normal or increased number of
      normoblasts in the bone marrow and an impaired in vitro colony formation. In the
      present study we analyzed whether this might be due to a disconnection between
      proliferation and differentiation. CD34+/CD36- sorted bone marrow cells of 18 MDS
      patients were cultured in a clonogenic and suspension culture assay in the
      presence of erythropoietin (Epo) and mast cell growth factor (MGF). Burst-forming
      units erythroid (BFU-E, 75 +/- 88/10(4) CD34+ cells, X +/- s.d.) and colony
      forming units E (CFU-E) were observed in eight of the 13 cases (62%) with
      refractory anemia with or without ring sideroblasts (RA and RARS) and one of the
      five cases with RA with excess of blasts or in transformation (RAEB and RAEB-T).
      Suspension cultures with CD34+/CD36- sorted cells with Epo plus MGF demonstrated
      an 8.9 +/- 6.5-fold expansion after 7 days in cases with >10 BFU-E/10(4)
      CD34+/CD36- cells while cases with <10 BFU-E/10(4) CD34+/CD36- cells demonstrated
      1.0 +/- 0.8-fold expansion especially in cases with RAEB/RAEB-T. FACS and
      morphology analysis after 7 days of suspension culture demonstrated partial
      differentiation along the erythroid lineage in cases with RA/RARS (75%) and
      RAEB/RAEB-T (66%) reflected by the presence of erythroblasts and normoblasts with
      variable expression of CD34, CD36 and Glycophorin A. In cases with erythroid
      colony formation 69 +/- 24% of the cells were CD34-/CD36+ and in cases with <10
      BFU-E/10(4) CD34+ cells 18 +/- 16% of cells were CD34-/CD36+. Iron staining
      showed the presence of ring sideroblasts in two cases with RARS indicating that
      the cells originate from the abnormal erythroid clone. Finally, it was shown that
      cases with an impaired proliferative response demonstrate an enhanced binding of
      Annexin-V on CD34+ cells during the first days of the cell suspension culture
      phase. These results suggest that a defect in the proliferative response is most
      pronouncedly expressed in MDS whereas a subpopulation of cells retain the
      capacity to differentiate between transition to a terminated stage.

PMID- 9639416
TI  - RAS, FMS and p53 mutations and poor clinical outcome in myelodysplasias: a 10
      year follow-up.
AB  - The molecular mechanisms underlying the development and evolution of
      myelodysplastic syndrome (MDS) are largely unknown. The increasing number of
      blast cells in the bone marrow correlate with poor prognosis and risk of
      developing acute leukemia. Such progression is frequently associated with
      increasing chromosomal abnormalities and genetic mutations. A cohort of 75 MDS
      patients were investigated for RAS, FMS and p53 mutations, and these molecular
      findings were related to cytogenetics, clinical status, transformation to acute
      leukemia, prognostic scores and survival. A mutation incidence of 57% (43/75) was
      found, with 48% (36/75) RAS mutations, 12% (9/75) FMS mutations and 8% (4/50) p53
      mutations. The mutation status for RAS and FMS was related to MDS subgroup,
      increasing with poor-risk disease. The highest incidence was in the chronic
      myelomonocytic leukemia (CMML) subgroup. The most frequent RAS mutations were of
      codon 12 and a predominance of FMS codon 969 mutations was observed. A
      statistically significant increased frequency of transformation to AML was
      observed in MDS patients harboring RAS or FMS mutations (P < 0.02). Patients with
      oncogene mutations had a significantly poorer survival compared with those
      without mutations at 2 years and at the end of the period of follow-up (P <
      0.02). Multivariate analysis including mutation, age, gender, diagnosis (FAB),
      cytogenetics and International score shows that the International score and
      mutation and age is the best predictive model of a poor outcome, (P < 0.0001).
      When the analysis was undertaken without the International score, mutation and
      gender was the best predictor of poor survival (P = 0.005). This study shows that
      oncogene mutation, indicative of genetic instability, is associated with disease
      progression and poor survival in MDS.

PMID- 9639417
TI  - Cyclin A1 is predominantly expressed in hematological malignancies with myeloid
      differentiation.
AB  - Cyclin A is a cell cycle regulatory protein that functions in mitotic and S phase
      control in mammalian cells. However, in contrast to other G1 phase regulatory
      proteins, such as cyclin D, retinoblastoma protein and p16INK4A, cyclin A seems
      not to be commonly involved in tumorigenesis. Recently, a second human cyclin A-
      cyclin A1--has been identified. In contrast to cyclin A which is expressed
      throughout embryonic development and in adult tissue, the expression of cyclin A1
      has been reported to be restricted to embryonic and germ line cells. We have
      confirmed the absence of cyclin A1 mRNA from normal peripheral blood leukocytes
      of seven healthy donors by single step reverse transcriptase-polymerase chain
      reaction (RT-PCR). Furthermore, we have examined the expression of cyclin A1 mRNA
      in 173 peripheral blood samples of 162 patients with various hematological
      malignancies. Cyclin A1 mRNA was detectable in 11 of 11 patients with acute
      myeloid leukemia, three of three patients with acute biphenotypic leukemia, eight
      of eight patients with myelodysplastic syndrome, 59 of 69 patients with chronic
      myelogenous leukemia (CML) at diagnosis, 13 of 15 patients with CML in blastic
      transformation, 10 of 18 patients with chronic lymphocytic leukemia, two of nine
      patients with essential thrombocythemia, and only two of 10 patients with acute
      lymphoblastic leukemia (ALL) with both cyclin A1 RT-PCR positive ALL leukemias
      being undifferentiated relapses. In addition, cyclin A1 mRNA was found in one of
      six leukapheresis products, harvested from individuals without hematological
      disorders. Taken together, cyclin A1 is expressed in the majority of myeloid and
      undifferentiated hematological malignancies as well as in normal hematopoietic
      progenitor cells. We conclude that cyclin A1, a protein potentially involved in
      G1/S phase progression of immature cells, might be necessary for proliferation of
      early hematopoietic progenitor cells and their leukemic counterparts being
      blocked at that stage of differentiation.

PMID- 9639418
TI  - Increased expression of the differentiation-defective granulocyte colony
      stimulating factor receptor mRNA isoform in acute myelogenous leukemia.
AB  - Granulocyte colony-stimulating factor (G-CSF) critically affects all stages of
      granulopoiesis by activating a signaling cascade initiated by dimerization of its
      receptor (G-CSFR). Five human G-CSFR isoforms have been identified (classes I-V).
      A quantitative polymerase chain reaction (Q-PCR) technique was used to examine
      the expression of these five isoforms in normal and leukemic myeloid cells. We
      demonstrated that neutrophils expressed predominantly the class I isoform and low
      levels of class IV isoform (IV/I = 0.037 +/- 0.005). No expression of the class
      II, class III, or class V isoform was detected. In contrast, all AML cell lines
      and acute myelogenous leukemia (AML) patient samples expressed increased relative
      amounts of the class IV isoform (IV/I = 0.047-0.350). When compared to normal
      immature myeloid cells, as represented by the CD34+ fraction of adult bone marrow
      (ABM) cells, three of eight AML cell lines and three of six AML patient samples
      expressed significantly increased levels of the class IV isoform relative to
      class I. This suggests that the increase in the relative expression of the class
      IV isoform seen in a considerable portion of AML cell samples is related to their
      leukemic phenotype. Given the inability of the class IV G-CSFR to drive myeloid
      maturation, the relative increase in class IV expression in AML cells may
      contribute to their aberrant response to G-CSF.

PMID- 9639419
TI  - Recombinant human megakaryocyte growth and development factor (MGDF) increases
      the numbers of megakaryocyte progenitor cells to normal values in long-term bone
      marrow cultures of patients with AML in first remission.
AB  - The megakaryopoietic potential in the bone marrow (BM) of patients in first
      remission after treatment for acute myelogenous leukaemia (AML) was investigated
      using long-term bone marrow cultures (LTC) stimulated with megakaryocyte growth
      and development factor (MGDF). The baseline number of megakaryocyte colony
      forming cells (Meg-CFC) was very low. However, there was a 10 to 100-fold
      increase of Meg-CFC in cultures treated with 10 ng/ml MGDF with mean numbers
      within the normal range for the first 4 weeks of culture with a 24-fold increase
      in their cumulative numbers. Similarly, a 12-fold increase in the numbers of
      megakaryocytes (MKs) was found by CD61 immunostaining. These effects were lost at
      the dose of 100 ng/ml. In contrast, the cumulative mean numbers of Meg-CFC in the
      control cultures from normal bone marrow (NBM) were not significantly different
      from those in cultures treated with 10 or 100 ng/ml MGDF. These results
      demonstrate that MGDF stimulates megakaryocytopoiesis in patients with AML in
      first remission, restoring the Meg-CFC compartment to normal values, a result
      with potential clinical implications for their treatment with autologous
      transplantation.

PMID- 9639420
TI  - The modulating effect of PSC 833, cyclosporin A, verapamil and genistein on in
      vitro cytotoxicity and intracellular content of daunorubicin in childhood acute
      lymphoblastic leukemia.
AB  - Resistance to anthracyclines is related to a poor prognosis in childhood acute
      lymphoblastic leukemia (ALL). Resistance to this class of drugs may (partly) be
      reversed by modulating agents, as has been demonstrated in a variety of cell
      lines. However, it is unknown which modulators may be of clinical benefit in
      childhood ALL. Therefore, we studied the modulating effect of PSC 833,
      cyclosporin A (CsA), verapamil (Vp) and genistein on daunorubicin (DNR)
      cytotoxicity, accumulation and retention in childhood ALL cells. DNR cytotoxicity
      was determined using the MTT assay; DNR accumulation, DNR retention and the
      expression of P-glycoprotein (P-gp), multidrug resistance-associated protein
      (MRP) and major vault protein/lung resistance protein (LRP) were determined by
      flow cytometry. In the majority of samples PSC 833 (19/26), CsA (22/26) and Vp
      (15/18) sensitized the cells to DNR whereas genistein made 25 out of 26 samples
      more resistant to DNR. The sensitizing effect on the cytotoxicity of DNR was
      median 1.2-fold using 2 microM PSC 833 (P = 0.025), 1.5-fold using 4 microM CsA
      (P = 0.003) and 1.6-fold using 6 microM Vp (P = 0.012) whereas the adverse effect
      of 25 microM genistein was median 1.8-fold (P < 0.0001). No relationship was
      found between the sensitizing effect of PSC 833, CsA or Vp and the degree of DNR
      resistance. In contrast, the adverse effect of genistein was largest in DNR
      sensitive samples (P = 0.003). The effect of each modulator on the cytotoxicity
      of DNR did not differ between initial and relapse ALL samples although the latter
      were median 1.4-fold more resistant to DNR (P = 0.005). Modulation of DNR
      cytotoxicity was not correlated with changes in the accumulated and retained
      intracellular DNR content or with the expression of P-gp, MRP and LRP. Besides
      genistein, PSC 833, CsA and Vp incidentally made ALL cells more resistant to DNR.
      CsA stimulated the leukemic cell survival in seven out of 26 samples, a
      phenomenon that was not related to the degree of DNR resistance. In conclusion,
      PSC 833, CsA and Vp but not genistein may be used to sensitize cells to DNR in
      childhood ALL. The data also indicate that not all patients may have a
      therapeutic benefit from these modulators. Therefore, an in vitro culture assay
      may be necessary to screen for patients who may benefit by a modulator in their
      therapy.

PMID- 9639421
TI  - Multiplication and death-type of leukemia cell lines exposed to very long-chain
      polyunsaturated fatty acids.
AB  - Polyunsaturated fatty acids (PUFA) may reduce cell multiplication in cultures of
      normal, as well as transformed, white blood cells. We assessed the sensitivity of
      14 different leukemia cell lines to PUFA by measuring cell number after 3 days of
      incubation. Ten of the examined cell lines were sensitive to 30, 60 and/or 120
      microM of arachidonic, eicosapentaenoic and docosahexaenoic acid, whereas four
      cell lines were resistant. The sensitivity to PUFA was not associated with any
      particular cell lineage, clinical origin or specific mRNA pattern of bcl-2 and c
      myc. Effects on cell viability were assessed by studying cell membrane integrity,
      DNA fragmentation and cell morphology. The sensitive cell lines Raji and Ramos
      died by necrosis and apoptosis, respectively, during incubation with
      eicosapentaenoic acid, whereas the viability of the resistant U-698 cell line was
      unaffected. The effects of EPA on Raji cells, was counteracted by vitamin E,
      indicating that lipid peroxidation was involved. However, apoptosis induced by
      eicosapentaenoic acid in Ramos cells, was unaffected by vitamin E, as well as
      eicosanoid synthesis inhibitors. In conclusion, our results indicate that a
      majority of leukemia cell lines are sensitive to PUFA. This sensitivity may be
      caused by induction of apoptosis or necrosis by very long-chain polyunsaturated
      fatty acids.

PMID- 9639422
TI  - Arginine butyrate downregulates p210 bcr-abl expression and induces apoptosis in
      chronic myelogenous leukemia cells.
AB  - Downregulation of bcr-abl expression in the chronic myelogenous leukemia cell
      line K562 using antisense oligonucleotides has been shown to enhance the
      sensitivity of the cells to apoptotic stimuli, suggesting that p210 bcr-abl, like
      bcl-2 functions as an anti-apoptosis factor (McGahon A et al, Blood 1994, 83:
      1179). In these experiments, the inhibition of p210 bcr-abl expression alone was
      not sufficient to induce apoptosis. We demonstrated that exposure to low doses
      (0.5 mM) of a butyric acid analog, arginine butyrate, was capable of inducing
      apoptosis in selected leukemia cell lines, including K562 cells, and in fresh
      leukemia cells from patients with chronic myelogenous leukemia. To further
      explore the mechanisms of this effect, we examined expression of p210 bcr-abl
      after butyrate exposure and found a dose-related inhibition of p210 bcr-abl
      protein without concordant change in other phosphoproteins, including the JAK-1
      kinase. Further analysis revealed that the inhibition of bcr-abl expression
      occurs due to transcriptional regulation of the bcr-abl gene by arginine
      butyrate. These results suggest that arginine butyrate and other butyrate analogs
      alone or in combination may be useful in the therapy of patients with chronic
      myelogenous leukemia or bcr-abl expressing acute leukemias.

PMID- 9639423
TI  - Hypermethylation of p15/ink4b/MTS2 gene is differentially implicated among non
      Hodgkin's lymphomas.
AB  - P15 (MTS2) gene is a candidate tumor suppressor gene localized adjacent to the
      p16 gene at 9p21. Deletions at the 9p21 region frequently affect both p16 and p15
      genes, however, mutations in the coding sequence of the p15 gene have not been
      found in the majority of tumors analyzed, including non-Hodgkin's lymphomas.
      Abnormal methylation of the promoter region of p15 has been recently described as
      an alternative mechanism of inactivation of this gene. We analyzed 72 non
      Hodgkin's lymphomas (NHL) for methylation at p15 exon 1 by PCR and Southern blot
      techniques using methylation-sensitive restriction enzymes. Abnormal methylation
      was found in eight cases (11%), most of them (three MALT, one anaplastic T cell
      lymphoma, one Burkitt and one follicular lymphoma) showing hypermethylation in
      the p16 gene also. In contrast, two pleomorphic T cell NHL showed a selective
      methylation at p15 gene, while the p16 gene remained unmethylated. The results
      show that methylation at the p15 gene is frequently associated with p16
      methylation in NHL, and suggest that selective methylation of p15, although
      uncommon, could be a specific alteration implicated in T cell NHL.

PMID- 9639424
TI  - CD34+, kit+, rhodamine123(low) phenotype identifies a marrow cell population
      highly enriched for human hematopoietic stem cells.
AB  - We hypothesized that human hematopoietic cells displaying a CD34+, kit-,
      rhodamine123(low) phenotype would be highly enriched for cells with stem-like
      properties. To test this hypothesis, we employed fluorescence activated cell
      sorting (FACS) to isolate cells with this phenotype from normal light density
      marrow mononuclear cells (MNC). CD34+, kit+, rhodamine123(low) cells comprised
      from 0.05-0.01% of the total MNC population. They were small, had scant
      cytoplasm, and contained nuclei with dense, hyperchromatic chromatin and
      inconspicuous nucleoli. Additional immunophenotyping revealed that these cells
      were CD33-, CD38-, CD20-, and glycophorin A-. When plated in semisolid cultures
      containing optimal concentrations of IL-3, GM-CSF, KL, EPO, IL-6, and IL-1 these
      cells did not form colonies. However, when cultured over irradiated stromal
      cells, cobblestone areas were observed to form after 3 weeks, and harvested cells
      were able to initiate long-term cultures. To further demonstrate that these cells
      were indeed stem like, we also tested their ability to engraft and mature in
      immunocompromised (SCID) mice. Irradiated (400 cGy) SCID mice were transplanted
      with 2 x 10(3) candidate stem cells which were then injected with recombinant
      human growth factors every other day. Two months post-transplant the animals were
      sacrificed. PCR and FACS analysis of marrow and spleen cell samples revealed the
      presence of cells expressing human CD45 consistent with engraftment of human stem
      cells and the establishment of murine-human chimerism. Moreover, MNC isolated
      from transplanted mice formed unambiguously human BFU-E, CFU-GM and B cell
      colonies when stimulated with the appropriate growth factors. Accordingly, we
      have identified a relatively rapid and simple mechanism for isolating primitive
      human hematopoietic cells with stem cell-like properties. We anticipate that this
      strategy will be useful for experimental and therapeutic applications that
      require human stem cells in quantity.

PMID- 9639425
TI  - Stroma-conditioned medium and sufficient prestimulation improve fibronectin
      fragment-mediated retroviral gene transfer into human primitive mobilized
      peripheral blood stem cells through effects on their recovery and transduction
      efficiency.
AB  - Mobilized peripheral blood stem cells (PBSC) are an attractive vehicle for cancer
      gene therapy. However these stem cells may have a reduced proliferative capacity
      due to previous cytotoxic chemotherapy treatment of the patient. In addition,
      primitive hematopoietic stem cells (HSC) from mobilized peripheral blood are
      almost exclusively quiescent, which makes it hard to induce proliferation in
      vitro and thus to improve stable transduction of introduced genes into a
      sufficiently large number of primitive stem cells. In this study CD34-selected
      mobilized PBSC from lymphoma and myeloma patients were used as target cells for
      retroviral-mediated gene transfer using a clinically relevant cell- and serum
      free supernatant transduction protocol. We have investigated various parameters
      that may contribute to an improvement of the poor transduction efficiency of the
      primitive HSC, including prestimulation time, the use of the carboxy-terminal
      fibronectin fragment CH-296, as well as stromal cell line conditioned media.
      Retroviral supernatant transduction in combination with CH-296 increased
      significantly the gene transfer efficiency as compared to supernatant alone and
      made the use of polycations redundant. Gene transfer of primitive HSC
      (cobblestone area forming cell (CAFC) week 6) was specifically improved when this
      procedure was preceded by a 5-day pre-culture period as compared to a 2-day
      transduction procedure. However, irrespective of the numerical recovery, the CAFC
      week 6 after retroviral transduction produced less long-term culture colony
      forming cells, suggesting a loss of individual stem cell quality. The addition of
      stroma-conditioned media during the pre-culture period did not affect the
      individual CAFC quality or transduction efficiency, but increased greatly the
      recovery of the total number of transduced and untransduced HSC leading to larger
      grafts containing higher numbers of transduced stem cells.

PMID- 9639426
TI  - Chromosomal analysis in multiple myeloma: cytogenetic evidence of two different
      diseases.
AB  - We report the cytogenetic results obtained in 81 multiple myeloma (MM) patients
      with abnormal karyotypes. Most karyotypes were complex with numerical and
      structural abnormalities but the analysis of chromosomal abnormalities allowed
      identification of two cytogenetic patterns depending on the chromosome number: a
      first hyperdiploid pattern (54%) with recurrent trisomies 3, 5, 7, 9, 11, 15 and
      19 and a second pattern (46%) showing either pseudodiploid, hypodiploid or near
      tetraploid karyotypes. Structural abnormalities were present in all but five
      hyperdiploid karyotypes, and frequently involved lymphoid breakpoints:
      immunoglobulin gene regions (36 cases) or chromosome 11q13 region (21 cases).
      Numerous other structural aberrations were detected; the most frequent involved
      chromosome 1 and chromosome 13. Structural abnormalities were significantly more
      frequent in the second hypodiploid group. When analyzing the results obtained in
      the 60 patients studied at the time of diagnosis, a prognostic correlation was
      found between the cytogenetic pattern and overall survival: hyperdiploid patients
      had a longer survival than patients belonging to the pseudo/hypo/near-tetraploid
      group (median survival 36.8 vs 18.2 months, P < 0.04). These results suggest that
      MM could correspond to two closely related diseases.

PMID- 9639427
TI  - Amplification of the TCL1 flanking region at 14q32.1 with no TCL1 gene
      transcription in a patient with peripheral T cell lymphoma.
AB  - Cytogenetic and molecular-genetic characteristics in peripheral T cell lymphoma
      (PTL) have not been well defined, except for those in adult T cell
      leukemia/lymphoma (ATL/L). Translocations and inversions involving a chromosome
      band 14q32 were extremely common abnormalities reported in PTL and ATL/L. We
      studied the involvement of TCL1, a recently isolated gene located in 14q32.1, in
      tumor tissues from 20 patients with PTL including three with 14q32 translocations
      by two color fluorescent in situ hybridization (FISH) using two cosmid probes
      flanking the TCL1 gene. The two cosmid signals were separated in none of them,
      but much increased in number in one tumor without 14q32 translocation, indicating
      that the TCL1 genomic region was amplified in this tumor. Reverse transcription
      polymerase chain reaction (RT-PCR), however, failed to detect the TCL1 transcript
      in the tumor. These findings suggest that an oncogene other than TCL1 may be
      located in 14q32.1, and its amplification may be involved in the neoplastic
      process of PTL.

PMID- 9639428
TI  - Abnormalities of the short arm of chromosome 12 in T cell prolymphocytic
      leukemia.
AB  - Abnormalities of the short arm of chromosome 12 are nonrandom events in T cell
      prolymphocytic leukemia (T-PLL). Fluorescence in situ hybridization (FISH)
      studies were performed in three patients with T-PLL and one patient with T cell
      peripheral lymphoma and rearrangement of 12p. Whereas the rearrangements of 12p
      were different in the four patients, a breakpoint centromeric to the ETV6 gene
      was present in the three T-PLL patients. In addition, loss of heterozygosity for
      a chromosomal segment telomeric to ETV6 with loss of the RAD52 locus was also
      shown by FISH studies. In contrast, the breakpoint was telomeric to ETV6 in the
      patient with peripheral lymphoma.

PMID- 9639429
TI  - Panhandle PCR: a technical advance to amplify MLL genomic translocation
      breakpoints.
AB  - Translocations involving a breakpoint cluster region of the MLL gene at
      chromosome band 11q23 are the most common molecular abnormalities in acute
      leukemias of infants and acute leukemias related to chemotherapy with DNA
      topoisomerase II inhibitors. Molecular cloning of MLL genomic breakpoints by PCR
      has previously been difficult because MLL has many translocation partners and
      several breakpoints involve unknown partner genes. We review a new approach to
      MLL genomic breakpoint cloning called panhandle PCR. By adding an oligonucleotide
      sequence to the unknown 3' partner gene that is complementary to a known 5' MLL
      sequence, we have been able to generate a genomic template with an intrastrand
      loop for PCR schematically shaped like a pan with a handle. The intrastrand loop
      contains the translocation breakpoint and unknown partner DNA, while the handle
      contains the known 5' sequence from MLL and a complement to that sequence.
      Primers both derived from MLL are used to amplify the breakpoint by panhandle
      PCR. Panhandle PCR offers the advantage of having specificity for the strand of
      interest at both primer annealing sites without requiring specific primers for
      the many partner genes of MLL. Panhandle PCR is a straightforward method that
      represents a technical advance in MLL genomic breakpoint cloning.

PMID- 9639430
TI  - Examination of a role for idiotypy in the disease remission of a long-term
      survivor of adult T cell leukemia treated with anti-Tac antibody.
AB  - The alpha chain of the interleukin 2 receptor (IL2R alpha; Tac) was targeted in
      clinical trials with adult T cell leukemia using murine anti-Tac antibody. Of 19
      patients, a single individual achieved a durable complete remission. The
      mechanism of this action by murine anti-Tac has not been defined. We examined the
      hypothesis that the maintenance of the long-term response after treatment might
      be related to induction of a network of anti-idiotypic antibodies, as proposed in
      other tumor settings. In contrast to anti-Tac non-responders, the patient was
      found to have produced a human anti-mouse antibody (HAMA) response, and
      specifically an anti-idiotypic (Ab2) response, that was readily detectable by
      standard assays 4 years after treatment. Using phage display antibody libraries,
      this response was shown to be monoclonal, consisting of a single IgG1,kappa
      antibody of moderate affinity. No evidence was found for anti-anti-idiotypic
      (Ab3) antibodies with reactivity for sTac, which might alternatively have
      maintained an autogenic human anti-Tac antibody response. An area of limited
      homology was noted between the Ab2 antibody and the IL2R in the domain of IL2
      binding, but no binding of Ab2 to IL2 could be shown that might have reduced
      endogenous ligand (IL2) concentrations. Similarly, no anti-anti-idiotypic (T3) T
      cell response was detected. Thus, we are unable to confirm features of idiotypy
      that could suggest a role in maintaining an anti-tumor response by anti-Tac
      antibody therapy.

PMID- 9639431
TI  - Prolonged molecular remission after PML/RAR alpha-positive autologous peripheral
      blood stem cell transplantation in acute promyelocytic leukemia: is relevant
      pretransplant minimal residual disease in the graft?
AB  - The contribution of residual malignant cells contaminating the autologous graft
      with the occurrence of post-transplant relapse in acute myeloid leukemia (AML) is
      still unclear. The presence of a specific molecular marker (the PML/RAR alpha
      rearrangement) in acute promyelocytic leukemia (APL) offers the opportunity to
      investigate better the pathogenesis of disease recurrence after transplant. We
      report an APL patient who received high-dose chemotherapy and peripheral blood
      stem cell (PBSC) autograft in second hematologic remission. Two leukaphereses
      that tested PML/RAR alpha positive by RT-PCR were obtained during the post
      reinduction hematopoietic recovery, while the patient also tested PCR positive in
      the BM, and was reinfused after myeloablative chemotherapy (BUCY4), when the
      patient had spontaneously converted to PCR negative in the marrow. At present, he
      remains in continuous molecular and hematologic remission 22 months after PBSC
      transplantation. This is the second report of an APL patient who was transplanted
      in molecular remission with a PML/RAR alpha-positive PBSC autograft. As in the
      previous report, the prolonged clinical and molecular remission experienced post
      transplant suggests that autologous PBSC infusion is still worthy of
      consideration for patients with APL in spite of the detection of PML/RAR alpha
      positive cells in the PBSC collections. Possible underlying mechanisms and the
      potential role of molecular monitoring of the graft, as well as the host, before
      and after transplant, in patients with APL undergoing autologous HSCT are also
      discussed.

PMID- 9639432
TI  - Impact of TEL/AML1-positive patients on age distribution of childhood acute
      lymphoblastic leukemia in Czech Republic. Pediatric Hematology Working Group in
      Czech Republic.

PMID- 9639433
TI  - Peripheral blood progenitor cells mobilized early at diagnosis in patients with
      chronic myelogenous leukemia contain very low amounts of BCR-ABL transcripts.

PMID- 9639434
TI  - Cytogenetic response induced by interferon alpha in the myeloproliferative
      disorder with eosinophilia, T cell lymphoma and the chromosomal translocation
      t(8;13)(p11;q12)

PMID- 9639435
TI  - Susceptibility of the adult T cell leukemia (ATL) cell lines to HHV-6B.

PMID- 9639436
TI  - Identification of integrated human herpesvirus 6 DNA in early pre-B cell acute
      lymphoblastic leukemia.

PMID- 9639437
TI  - Fulminant hepatosplenic B cell lymphoma in a young patient with HCV-chronic
      hepatitis.

PMID- 9639438
TI  - Late relapse in BCR/ABL-positive patients after non-intensive chemotherapy.

PMID- 9639439
TI  - Pupil involvement in patients with diabetes-associated oculomotor nerve palsy.
AB  - OBJECTIVE: To derive a reliable estimate of the frequency of pupil involvement in
      patients with diabetes-associated oculomotor nerve palsy. PATIENTS AND METHODS:
      In this prospective study, standardized enrollment criteria were employed to
      identify 26 consecutive patients with diabetes-associated oculomotor nerve palsy
      who were evaluated in a referral-based, outpatient neuro-ophthalmology practice.
      A pupil ruler accurate to within 0.5 mm was used to measure pupil diameters using
      a standardized procedure. The degree of anisocoria, if present, was recorded at
      each office visit until the ophthalmoplegia had resolved. Descriptive statistics
      were used to identify the frequency and characteristics of pupil involvement.
      RESULTS: Internal ophthalmoplegia occurred in 10 (38%) of 26 patients. The size
      of the anisocoria was 1 mm or less in most patients. None of the patients had a
      fully dilated unreactive pupil. CONCLUSIONS: Pupil involvement in patients with
      diabetes-associated oculomotor nerve palsy occurs more often than has been
      previously recognized, although the degree of anisocoria in any 1 patient is
      usually only 1 mm or less. Some characteristics of the internal ophthalmoplegia
      may help to distinguish diabetic ophthalmoplegia from injury of the oculomotor
      nerve caused by aneurysmal compression.

PMID- 9639440
TI  - Angle-closure glaucoma associated with occult annular ciliary body detachment.
AB  - OBJECTIVE: To evaluate the role of annular ciliary body detachment in the
      development of postoperative angle-closure glaucoma. DESIGN: Case series.
      SETTING: Tertiary care glaucoma referral center. METHODS: High-resolution,
      anterior segment ultrasound biomicroscopy, ophthalmoscopy, and B-scan
      ultrasonography were performed on 6 eyes of 6 patients with a clinical diagnosis
      of postoperative malignant glaucoma. RESULTS: Each eye had an elevated
      intraocular pressure, a shallow anterior chamber, 1 or more patent iridectomies,
      and no ophthalmoscopic or B-scan ultrasound evidence of serous or hemorrhagic
      ciliochoroidal detachment. Ultrasound biomicroscopy revealed annular ciliary body
      detachment in each eye. In 4 eyes, observation with topical medical treatment was
      associated with deepening of the anterior chamber, reduced intraocular pressure,
      and resolution of the detachment. Drainage of the supraciliary fluid was
      performed in 2 eyes. CONCLUSION: Occult, annular, serous detachment of the
      ciliary body may cause postoperative angle-closure glaucoma. This entity is
      clinically indistinguishable from malignant glaucoma. Ultrasound biomicroscopy
      facilitates the diagnosis.

PMID- 9639441
TI  - Transforming growth factor beta2 in the vitreous in proliferative diabetic
      retinopathy.
AB  - OBJECTIVE: To evaluate the hypothesis that transforming growth factor beta2 (TGF
      beta2) is involved in the cause of proliferative diabetic retinopathy (PDR).
      METHODS: We assayed TGF-beta2 levels in the vitreous of patients with PDR and
      other vitreoretinal disorders. Forty-nine vitreous specimens were obtained from
      eyes of patients with PDR undergoing vitrectomy, and 19 vitreous specimens from
      nondiabetic subjects served as controls. We assessed TGF-beta2 levels using an
      enzyme-linked immunosorbent assay. Both mature and total TGF-beta2 levels were
      quantified. RESULTS: The mean (+/- SD) total levels of TGF-beta2 were 2634 (+/-
      1652) pg/mL in the patients with PDR and 1305 (+/- 972) pg/mL in controls. The
      mean (+/- SD) levels of mature TGF-beta2 were 244 (+/- 316) pg/mL in patients
      with PDR and 79 (+/- 81) pg/mL in controls. Total and mature TGF-beta2 levels
      were significantly greater in patients with PDR (total TGF-beta2, P <.001; mature
      TGF-beta2, P <.01). Mature TGF-beta2 levels were higher in the vitreous of
      patients who had severe fibrous proliferation. CONCLUSION: The results indicate
      increased levels of both total and mature TGF-beta2 in the vitreous of patients
      with PDR, suggesting that TGF-beta2 plays an important role in the pathogenesis
      of PDR.

PMID- 9639442
TI  - Histopathologic and ultrastructural findings of surgically excised choroidal
      neovascularization. Submacular Surgery Trials Research Group.
AB  - OBJECTIVE: To study the histologic and ultrastructural features of surgically
      excised choroidal neovascularization (CNV) from patients who had undergone
      submacular surgery. MATERIALS AND METHODS: Voluntarily submitted surgically
      excised CNV specimens from a subset of specimens obtained by the Submacular
      Surgery Trials Research Group between January 1, 1994, and December 31, 1996,
      were available for this study. The specimens were routinely processed for
      transmission electron microscopic examination. The largest horizontal and
      vertical dimensions, cellular and extracellular constituents, and relationship of
      the CNV to the neurosensory retina and retinal pigment epithelium (RPE) were
      recorded. RESULTS: Seventy-eight surgical specimens were obtained from 160
      patients treated surgically in Submacular Surgery Trials centers. Sixty-one (78%)
      were from patients with age-related macular degeneration (ARMD) and 17 (22%) were
      from patients with ocular histoplasmosis syndrome or idiopathic causes (hereafter
      referred to as the non-ARMD group). The histologic diagnosis was fibrovascular
      tissue, fibrocellular tissue, or hemorrhage in all cases. Vascular endothelium
      and RPE were the most common constituents of the CNV. Basal laminar deposit was
      only present in CNV from patients with ARMD. Age-related macular degeneration
      specimens were larger (mean +/- SD, 2042 [+/- 1175] x 320 [+/- 185] microm vs
      1498 [+/- 792] x 227 [+/- 166] microm) and were more likely to have a sub-RPE
      (beneath the RPE) component than non-ARMD specimens. CONCLUSIONS: All evaluated
      surgically excised CNV specimens in this study from patients enrolled in the
      Submacular Surgery Trials consisted of fibrovascular tissue, fibrocellular
      tissue, or hemorrhage. Surgically excised CNV associated with ARMD in this series
      was larger and often was located beneath the RPE compared with non-ARMD CNV,
      although fewer than half of all the specimens could be oriented by topographic
      relationship to the RPE.

PMID- 9639443
TI  - Long-term follow-up of iatrogenic phototoxicity.
AB  - OBJECTIVE: To evaluate the outcomes of a group of patients who suffered
      iatrogenic phototoxic injury. METHODS: The medical records of 24 patients (24
      eyes) with iatrogenic phototoxicity from 3 medical centers were reviewed. We
      report the findings from long-term follow-up of these patients with particular
      attention to visual outcome, type and duration of procedure, and location of the
      phototoxic lesion. RESULTS: Phototoxic injury occurred after anterior segment
      surgery in 20 eyes and after vitrectomy in 4 eyes. The mean duration of surgery
      was 109 minutes; there was no statistically significant difference in duration
      between the anterior segment procedures and the vitrectomies. Mean final visual
      acuity was 20/40 for all cases (range, 20/15 to counting fingers) and 20/25 for
      all anterior segment cases. In vitrectomized eyes, the mean final visual acuity
      was 20/900. Phototoxic lesions tended to spare the fovea after anterior segment
      surgery and involve the foveal center after vitrectomy. CONCLUSIONS: In general,
      patients who suffer phototoxicity do well, and the prognosis is good for
      extrafoveal lesions. Foveal injury, which often occurs with vitrectomy, usually
      leads to a worse visual outcome. The development of choroidal neovascularization
      may have an effect on the ultimate visual outcome as well.

PMID- 9639444
TI  - Effects of fenretinide (4-HPR) on dark adaptation.
AB  - OBJECTIVES: To assess the alterations in dark adaptation induced by low (200
      mg/d) doses of fenretinide (4-HPR), to assess whether these effects were
      cumulative and whether they were reversible, and to attempt to elucidate the
      mechanism underlying the changes in night vision. DESIGN: Case series. SETTING:
      Outpatient eye clinic. PATIENTS: Twenty-two women enrolled in a breast cancer
      chemoprevention trial, and 18 normal control subjects. INTERVENTION: Measurements
      of absolute luminance thresholds during dark adaptation. MAIN OUTCOME MEASURES:
      Parameters of an exponential model of the dark-adaptation function before,
      during, and after administration of fenretinide. RESULTS: The most conspicuous
      effect of fenretinide on dark adaptation was a significant delay in the timing of
      the rod-cone break (P<.001). A minimal elevation of the final cone threshold was
      also observed. These effects were reversible after fenretinide therapy was
      discontinued and did not seem to be cumulative. An inverse relationship between
      delay of the rod-cone break and plasma retinol concentration was found.
      CONCLUSION: The dose of fenretinide used in this study produced clearly
      measurable, but not severe, changes in night vision, which were rarely
      symptomatic.

PMID- 9639445
TI  - Vertical location of the corneal light reflex in strabismus photography.
AB  - OBJECTIVE: To improve the clinical documentation of strabismus by mathematically
      predicting and clinically verifying the location of a fixation target that
      produces a vertically centered corneal light reflex (first Purkinje image) in
      clinical photographs of the eye using a standard photographic flash unit.
      MATERIALS AND METHODS: Mathematical modeling of the corneal light reflex during
      clinical photography was based on the schematic eye. Clinical photographs were
      taken using a range of fixation targets located between the center of the camera
      lens and the center of the flash. Image quality was also assessed subjectively.
      RESULTS: Optimum vertical centration of the corneal light reflex was predicted
      and produced when the fixation target was located one fifth of the distance from
      the center of the flash to the center of the camera lens. Placement of the flash
      below, rather than above, the camera lens provided more uniform illumination of
      the patient's eyes and face. Decreasing the distance between the camera lens and
      the flash minimized the severity of these artifacts. CONCLUSIONS: A poorly
      positioned corneal light reflex makes it difficult to identify the fixing eye in
      photographs of patients with strabismus, especially when vertical strabismus is
      present. Adoption of the aforementioned protocol will reproduce the appearance of
      coaxially viewed corneal light reflexes and provide much-needed standardization
      for strabismus case presentation.

PMID- 9639446
TI  - Development of tearing in preterm and term neonates.
AB  - BACKGROUND: Although term and preterm infants have the capacity to secrete tears,
      the relative contribution of basal and reflex secretion of tears has not been
      previously assessed together in a prospective study. This information potentially
      has practical clinical importance. OBJECTIVES: To measure basal and reflex tear
      secretion in preterm (30-37 weeks after conception) and term (38-42 weeks)
      newborns and to determine the developmental pattern of tear production. METHODS:
      Tear secretion was evaluated by applying Schirmer tear test strips to the
      inferior fornix for 5 minutes before (reflex plus basal secretion) and after
      (basal secretion) applying a topical anesthetic agent. RESULTS: Seventy infants
      (36 preterm and 34 term) were tested. Mean (+/- SD) basal tear secretion was 6.2
      (+/- 4.5) mm in preterm and 9.2 (+/- 4.3) mm in term infants and increased
      progressively with increasing weight (P<.001) for all newborns. Mean (+/- SD)
      reflex tear secretion was 7.4 (+/- 4.8) mm in preterm and 13.2 (+/- 6.5) mm in
      term infants and also increased with increasing weight (P<.001) for all newborns.
      CONCLUSIONS: Preterm infants have reduced reflex and basal tear secretion. This
      may mask the diagnosis of a nasolacrimal duct obstruction, concentrate topically
      applied medications, and allow corneas to quickly become dry during
      ophthalmological examination and treatment. By term, tear production in newborns
      is similar to that in adults.

PMID- 9639448
TI  - The effect of age on the retardation of axial elongation following a lensectomy
      in infant monkeys.
AB  - OBJECTIVE: To determine the effect of age on the retardation of axial elongation
      in neonatal monkey eyes following the extraction of the crystalline lens.
      METHODS: A monocular lensectomy was performed on 4 rhesus monkeys when they were
      4 days, 2 weeks, 7.5 months, and 1 year of age. Longitudinal measurements of
      axial lengths and keratometry readings were made. RESULTS: The aphakic eye was
      1.7 mm shorter than the unmanipulated fellow eye in the monkey undergoing surgery
      at 4 days of age and 1.1 mm shorter in the monkey undergoing surgery at 2 weeks
      of age. However, the aphakic eyes were only 0.2 mm and 0.1 mm shorter than their
      unmanipulated fellow eyes, respectively, in the monkeys undergoing surgery at 7.5
      months and 1 year of age. CONCLUSIONS: The retardation of axial elongation
      following a lensectomy in infantile monkey eyes is age dependent. Little effect
      is observed in monkeys aged 7.5 months or older.

PMID- 9639447
TI  - Trifluridine, cidofovir, and penciclovir in the treatment of experimental
      herpetic keratitis.
AB  - OBJECTIVE: To compare trifluridine eyedrops, cidofovir eyedrops, and penciclovir
      ophthalmic ointment for the treatment of herpes simplex virus type 1 keratitis.
      METHODS: New Zealand white rabbits were infected with the McKrae strain of herpes
      simplex virus type 1. Three days after viral inoculation, the rabbits were
      randomly assigned to treatment with 1% trifluridine, 0.2% cidofovir, 3%
      penciclovir ointment, or phosphate-buffered saline (for control) on various
      schedules. The severity of keratitis was graded in a masked manner. RESULTS:
      Treatment with any of the antiviral drugs resulted in significantly less severe
      keratitis than treatment with phosphate-buffered saline. There was no
      statistically significant difference between eyes given trifluridine 2, 4, or 7
      times a day and eyes given cidofovir 2 times a day (P=.06, P=.43, and P=.19,
      respectively, using the F test of the analysis of variance). Cidofovir given
      twice a day was significantly more effective than penciclovir given either 2 or 4
      times a day (P<.001 and P=.002, respectively). Even with once-a-day dosage, all 3
      drugs were significantly more effective than phosphate-buffered saline (P<.001
      for all). There was no significant difference between once-a-day trifluridine and
      cidofovir treatments (P=.17). Trifluridine administered 5 times a day was as
      effective as 1% cidofovir. A similar degree of punctate keratitis was seen after
      4 to 5 days in eyes treated with trifluridine at the highest frequency, 1%
      cidofovir, or penciclovir ointment. CONCLUSION: Trifluridine treatment was highly
      effective in this rabbit model, even when given only once a day. Treatment with
      cidofovir was as effective as that with trifluridine. CLINICAL RELEVANCE:
      Cidofovir and penciclovir treatments may prove to be effective against epithelial
      keratitis. Clinical trials of trifluridine, cidofovir, and penciclovir with lower
      treatment frequencies appear to be warranted.

PMID- 9639449
TI  - Retinal vessel changes in galactose-fed dogs.
AB  - BACKGROUND: Retinal lesions similar to those in human early-stage diabetic
      retinopathy have been reported to occur in dogs fed galactose for long periods.
      Investigations of retinal changes, however, have been limited to studies of the
      intact retinal vasculature isolated by trypsin digestion. OBJECTIVE: To document
      the onset and progression of retinal lesions in galactose-fed dogs by the common
      clinical techniques of fundus color photography and fluorescein angiography.
      METHODS: Fourteen 6-month-old male beagles made aphakic in 1 eye were divided
      into a control group (4 dogs), receiving a diet containing 30% cellulose, and a
      galactosemic group (10 dogs), receiving a diet containing 30% galactose. The
      progression of retinal changes in these dogs was periodically monitored by color
      fundus photography and fluorescein angiography. RESULTS: Dogs fed a 30% galactose
      diet for 28 to 41 months were observed by fluorescein angiography and color
      fundus photography to develop, in order of frequency, microaneurysms, retinal
      hemorrhages, intraretinal microvascular abnormalities, retinal nonperfused areas,
      and varicose and serpiginous veins. These findings are similar to the early
      clinical retinal changes observed in humans with diabetes. CONCLUSION: These
      results confirm that galactosemic dogs are an appropriate and suitable animal
      model for investigating human diabetic retinopathy.

PMID- 9639450
TI  - A novel mutation in the GLC1A gene causes juvenile open-angle glaucoma in 4
      families from the Italian region of Puglia.
AB  - BACKGROUND: Primary open-angle glaucoma encompasses a complex of potentially
      blinding ocular diseases characterized by a normal-appearing angle of the
      anterior chamber, a characteristic degeneration of the optic nerve with resultant
      typical visual field defects, and usually, an elevated intraocular pressure. It
      can be subdivided into 2 groups according to the age at onset: the more prevalent
      chronic open-angle glaucoma diagnosed after 40 years of age, and the less common
      juvenile form, which occurs between 3 years of age and early adulthood. A locus
      for primary open-angle glaucoma (GLC1A) has been mapped to a 3-centimorgan region
      of the long arm of chromosome 1 (1q23-25). Recently, the myocilin (MYOC) gene,
      located in this chromosomal interval, has been found mutated in several patients
      affected by primary open-angle glaucoma. OBJECTIVE: To describe the clinical and
      molecular genetic features of 4 pedigrees affected by autosomal dominant juvenile
      open-angle glaucoma, all from the Italian region of Puglia. METHODS: Clinical
      study, gonioscopy, automated perimetry, and DNA analysis were performed on
      several members of the 4 families. RESULTS: We identified a new molecular defect
      (1177GACA-->T) in the third exon of the GLC1A gene. This mutation is present in
      all affected persons and in 2 still phenotypically normal persons. CONCLUSION:
      Our results are important for diagnostic purposes because it is now possible to
      identify asymptomatic carriers, for whom clinical surveillance for the early
      detection and treatment of glaucoma may be suggested.

PMID- 9639451
TI  - Managing oculomotor nerve palsy.

PMID- 9639452
TI  - Options in the management of malignant glaucoma.

PMID- 9639453
TI  - Multifocal choroiditis: clinicopathologic correlation.
AB  - Many of the white dot syndromes are considered to have a granulomatous
      pathogenesis. The histopathologic characteristics of this case of multifocal
      choroiditis seen within 15 months of apparent clinical onset show that the white
      dot lesions were nongranulomatous perivascular choroidal infiltrates, consisting
      mainly of B lymphocytes. Early choroidal neovascularization was also seen.

PMID- 9639455
TI  - Pars plana tube insertion of aqueous shunt with vitrectomy in malignant glaucoma.

PMID- 9639454
TI  - Sarcoidosis with orbital tumor outside the lacrimal gland: initial manifestation
      in 2 elderly white women.
AB  - Two elderly white women (aged 72 and 87 years) were first seen with painless,
      unilateral orbital swelling. Orbital scanning revealed masses infiltrating the
      soft tissue around the eye. Biopsy results showed nodular, noncaseating
      granulomas consistent with sarcoidosis. One patient's workup revealed systemic
      manifestations of sarcoidosis at the time of examination with hilar
      lymphadenopathy noted on gallium scan; the other refused a complete systemic
      workup. The orbital tumors resolved with systemic prednisone therapy. To our
      knowledge, our 87-year-old patient is the oldest to be seen with orbital
      sarcoidosis. These 2 patients demonstrate that this diagnosis must be considered
      with orbital tumors in the elderly and in unusual locations, such as these which
      occurred outside the lacrimal gland.

PMID- 9639456
TI  - Acute microcystic corneal epitheliopathy after daily soft contact lens wear.

PMID- 9639457
TI  - Repair of a complex retinal detachment with proliferative vitreoretinopathy in an
      eye with extreme scleral thinning.

PMID- 9639458
TI  - Parafoveal telangiectasia in association with CREST syndrome.

PMID- 9639459
TI  - Low-dose external beam irradiation for bilateral diffuse choroidal hemangioma.

PMID- 9639460
TI  - Electrophysiologic evaluation of a patient with peripheral visual field
      contraction associated with vigabatrin.

PMID- 9639461
TI  - Iris fixation of a decentered silicone plate haptic intraocular lens: double knot
      technique.

PMID- 9639462
TI  - Intraorbital metallic foreign body.

PMID- 9639463
TI  - Acute thioridazine retinopathy.

PMID- 9639464
TI  - Use of blue-on-yellow perimetry to demonstrate quadrantanopia in multiple
      sclerosis.

PMID- 9639465
TI  - Erbium-YAG laser ablation: the myth of 1-microm penetration.

PMID- 9639466
TI  - Optic nerve hypoplasia diagnosis should be confirmed by accurate measurements.

PMID- 9639467
TI  - Interaction between acetazolamine and cyclosporine.

PMID- 9639468
TI  - Botulinum toxin treatment of infantile esotropia in children.

PMID- 9639469
TI  - Showing abnormal slitlamp findings.

PMID- 9639471
TI  - Complement activation in sudden deafness.
AB  - OBJECTIVE: To test whether complement activation is associated with sudden
      deafness. DESIGN: Plasma samples obtained from patients in the acute phase of
      sudden deafness were analyzed for complement activation measured by C3bc levels
      and terminal complement complex. Comparisons were made with plasma samples from
      healthy controls. PATIENTS: Twenty-five adult patients with unilateral sudden
      deafness. The criteria for inclusion were symptoms of hearing loss for not longer
      than 14 days and a hearing loss of 35 dB or more measured at entry. RESULTS:
      Levels of C3bc were higher in patients compared with controls (P<.001). There
      were no differences in the formation of terminal complement complex in patients
      and controls. CONCLUSIONS: The elevated levels of C3bc in patients with sudden
      deafness indicate an activation of the first part of the complement cascade and
      therefore suspected inflammatory causes. Measurements of C3bc levels might
      identify patients with sudden deafness who would benefit from treatment with anti
      inflammatory drugs.

PMID- 9639470
TI  - Functional results of primary closure vs flaps in oropharyngeal reconstruction: a
      prospective study of speech and swallowing.
AB  - BACKGROUND: The preservation of speech and swallowing function is the primary
      goal when reconstructing soft tissue defects in the oral cavity or oropharynx.
      The type of reconstructive procedure used should be based on outcome data
      examining speech and swallowing function; yet, there is a paucity of such
      information. OBJECTIVES: To present the results of a multi-institutional
      prospective study of speech and swallowing function before and after soft tissue
      reconstruction of the oral cavity and oropharynx, and to compare 3 methods of
      reconstruction with respect to speech and swallowing function: primary closure,
      distal myocutaneous flap, and microvascular free flap. DESIGN: Prospective case
      comparison study. SETTING: Four leading head and neck cancer institutions.
      PATIENTS: The patients were selected from a database of 284 patients treated at
      the different institutions. The patients were matched for the location of the
      oral cavity or oropharyngeal defect and the percentage of oral tongue and tongue
      base resection. Those patients who had previous speech and swallowing deficits
      and patients in whom postoperative fistulas or wound infections developed were
      excluded from the study. METHODS: The patients underwent speech and swallowing
      evaluation preoperatively and 3 months after healing. This evaluation included
      videofluoroscopic studies of swallowing and tests of speech intelligibility and
      sentence articulation. Videofluoroscopy provided measures of swallowing
      efficiency and bolus movement. Liquid and paste consistencies were used in
      evaluating swallowing function. MAIN OUTCOME MEASURE: The functional results of
      the reconstruction. RESULTS: Patients who had primary closure were more efficient
      at swallowing liquids, had less pharyngeal residue, a longer oral transit time
      with paste, and higher conversational intelligibility than patients who underwent
      reconstruction with a distal flap. Compared with patients who underwent
      reconstruction with a free flap, those who had primary closure had more efficient
      swallowing of liquids, less pharyngeal residue, and shorter pharyngeal delay
      times with paste. No difference in the speech and swallowing function existed
      between patients treated with distal myocutaneous flaps and those treated with
      microvascular free flaps. CONCLUSION: Contrary to the current theory of oral and
      oropharyngeal reconstruction, we found that the use of primary closure resulted
      in equal or better function than the use of flap reconstruction in patients with
      a comparable locus of resection and percentage of oral tongue and tongue base
      resection.

PMID- 9639472
TI  - Perineural invasion in squamous cell carcinoma of the head and neck.
AB  - OBJECTIVE: To determine if perineural invasion (PNI) of small nerves affects the
      outcome of patients with squamous cell carcinoma (SCC) of the upper aerodigestive
      tract. DESIGN: Retrospective clinicopathological study of patients with at least
      2 years of follow-up and with negative margins and no prior, synchronous, or
      metachronous SCC. SETTING: Academic otolaryngology department. PATIENTS: One
      hundred forty-two patients who had SCC of the oral cavity, oropharynx and
      hypopharynx, or larynx resected between 1981 and 1991. INTERVENTION: Surgery with
      or without adjuvant therapy. MAIN OUTCOME MEASURES: Local recurrence was examined
      with respect to PNI, nerve diameter, and microvascular or microlymphatic
      invasion. Perineural invasion was correlated with lymph node metastasis,
      extracapsular spread, and survival. RESULTS: Perineural invasion of nerves less
      than 1 mm in diameter was present in 74 patients, lymphatic invasion in 53, and
      vascular invasion in 9. Perineural invasion was significantly associated with
      local recurrence (23% for PNI vs 9% for no PNI; P=. 02), and disease-specific
      mortality (54% mortality for PNI vs 25% for no PNI; P<.001). With extralaryngeal
      tumors, PNI was associated with nodal metastasis (73% vs 46%; P=.03). Perineural
      invasion was not associated with extracapsular spread (P=.47). Microvascular
      invasion, lymphatic invasion, and nerve diameter were not significantly related
      to local recurrence. CONCLUSIONS: Perineural invasion of small nerves is
      associated with an increased risk of local recurrence and cervical metastasis and
      is, independent of extracapsular spread, a predictor of survival for patients
      with SCC of the upper aerodigestive tract.

PMID- 9639473
TI  - Peritumoral CD1a-positive dendritic cells are associated with improved survival
      in patients with tongue carcinoma.
AB  - OBJECTIVES: To determine if survival and recurrence rates for patients with
      squamous cell carcinoma of the tongue correlate with the degree of dendritic cell
      (DC) infiltration of the primary tumor or adjacent tongue tissue and if there is
      an association between tumor or nodal stage and DC infiltration. DESIGN: Hospital
      and office medical records were reviewed to obtain 5-year follow-up data.
      Original pathology specimens were recut and stained for the cell surface markers
      S100 and CD 1a. The number of DCs present in the specimens was quantified
      microscopically and compared statistically with patient outcome and staging.
      SETTING: A university hospital. PATIENTS: All patients who underwent resection of
      primary squamous cell carcinoma of the tongue from January 1, 1987, through
      December 31, 1990, for whom 5-year follow-up data and original pathology
      specimens were available (N=43). MAIN OUTCOME MEASURES: Time to recurrence,
      death, or both. RESULTS: Patients who had greater numbers of CD1a-positive DCs
      adjacent to tumor had improved survival (P=.02) and decreased recurrence rates
      (P=.06). The other subpopulations of DCs examined were not associated with
      survival or recurrence. In addition, the number of CD 1a-positive DCs in
      peritumoral epithelium decreased as the tumor stage increased (P=.01) and if
      nodal metastases were present (P=.05). CONCLUSIONS: Dendritic cells are antigen
      presenting cells that are thought to play a major role in the antitumor immune
      response. The CD1a surface antigen has been shown to mediate T-cell interactions.
      The association between CD1a-positive peritumoral DCs and patient outcome
      suggests an important function for this cell population.

PMID- 9639474
TI  - The ectopic parathyroid adenoma: a cost justification for routine preoperative
      localization with technetium Tc 99m sestamibi scan.
AB  - OBJECTIVES: To evaluate the cumulative costs of failure to identify the ectopic
      parathyroid adenoma when exploration without preoperative localization is
      performed and to compare these costs with the expenses of routine preoperative
      localization in every patient. DESIGN: A consecutive series of 59 patients with
      primary hyperparathyroidism studied with preoperative scans using technetium Tc
      99m sestamibi and ultrasound was submitted to a cost analysis. A subset of 5
      cases of ectopic adenomas, presumed to be unidentifiable on routine surgery, was
      similarly analyzed. SETTING: Academic tertiary referral center. METHODS: The
      operative, anesthesia, hospitalization, imaging, and physician reimbursement
      costs of a failed exploration are compared with the costs of preoperative
      technetium Tc 99m sestamibi and ultrasound scans in every patient. RESULTS: Two
      cases of mediastinal parathyroid adenomas in this consecutive series of 59
      patients were given a theoretical cost, including hospitalization, physician
      reimbursement, and anesthesia fees. These costs were based on a failed cervical
      exploration and extracted from the record of an actual patient who underwent such
      a process at the University of Vermont, Burlington, in 1995. In addition, the
      records of 2 patients with intrathyroidal adenomas were submitted to the same
      theoretical cost analysis with the exception that these patients were assumed to
      have adenomas that could be discovered after prolonged cervical exploration and
      thyroid lobectomy. The net management and imaging costs for 4 cases of ectopic
      parathyroid adenomas undergoing theoretical failed exploration are compared with
      the cost of obtaining routine technetium Tc 99m sestamibi and ultrasound scans
      for each of the 59 patients. CONCLUSION: The added cost of protracted or failed
      cervical exploration nearly neutralized the costs of a routine preoperative
      localization with technetium Tc 99m sestamibi and ultrasound scans.

PMID- 9639475
TI  - Morphometry of paranasal sinus anatomy in chronic rhinosinusitis: a pilot study.
AB  - OBJECTIVES: To test the null hypothesis that there is no relationship between
      anatomical variations around the ostiomeatal complex and a predisposition to
      chronic rhinosinusitis and to define such variations with increased precision.
      DESIGN: Case-control study of anatomical variations in diseased and normal
      sinuses. Eight homologous landmarks defining the ostiomeatal complex were located
      on coronal computed tomographic scans, and their x and y coordinates were
      digitized using image analysis. SUBJECTS: Ten patients with unilateral sinus
      disease and 10 subjects without sinus disease (scanned for facial pain) who were
      selected retrospectively by case-note analysis. RESULTS: Logistic regression
      showed that the only significant spatial change predictive of a person with
      rhinosinusitis was the vertical position of the middle turbinate (P=.04),
      although this was not confirmed by Wilcoxon testing (P>.10). When examined by
      sinus, however, the horizontal position of the uncinate process was more
      laterally placed in persons with rhinosinusitis (P=.01), confirmed on Wilcoxon
      testing (P=.04), but there was no significant difference when compared with
      sinuses in persons without rhinosinusitis. CONCLUSIONS: Our findings suggest that
      there are no anatomical differences within the ostiomeatal complex between
      patients with and without rhinosinusitis. Patients with rhinosinusitis, however,
      are more likely to develop it in the side with a more laterally positioned
      uncinate process. Further studies, with more patients and more advanced
      techniques, including thin-plate spline analysis, are indicated.

PMID- 9639476
TI  - Posterior cricoidotomy lumen augmentation for treatment of subglottic stenosis in
      children.
AB  - OBJECTIVES: To determine the results of posterior cricoidotomy lumen augmentation
      in the treatment of moderate and severe subglottic stenosis in children, and to
      assess the effect of this surgery on the growth of the larynx in young children.
      DESIGN: A 17-year retrospective study. PATIENTS AND METHODS: Thirteen children
      with moderate and severe subglottic stenosis who underwent posterior cricoidotomy
      lumen augmentation from 1980 to 1996. Eight children (62%) were male and 5 (38%)
      were female. The average age was 4.7 years (age range, 8 months to 15 years). Six
      (46%) of the 13 children were younger than 3 years. Nine children (69%) had
      acquired subglottic stenosis, 3 of whom had a combined subglottic-posterior
      glottic stenosis, and 4 (31%) had congenital subglottic stenosis. All the
      children already had a tracheotomy tube placed and had undergone treatment at our
      clinic or at other institutions. The surgical procedure we used included a
      cricoid lamina split with grafting (2 children with costal cartilage graft and 11
      with buccal mucosal graft) and stenting. RESULTS: Twelve (92%) of the 13 children
      underwent decannulation, and 1 (8%) is still undergoing treatment: decannulation
      is expected to be carried out in the near future. Of the 12 children who
      underwent decannulation, 9 demonstrated good postoperative voice quality and 3,
      who had combined subglottic-posterior glottic stenosis, developed impaired voice
      function. Following stent removal, all children experienced some degree of
      difficulty in swallowing saliva and liquids, which was soon overcome. No evidence
      of surgery-induced laryngeal growth impairment in younger children was observed.
      CONCLUSIONS: The posterior cricoidotomy lumen augmentation is a safe and
      effective technique for the treatment of moderate and severe subglottic stenosis
      in children of any age. This study lends further support to the assertion that
      external surgery does not affect the growth of the larynx in younger children.

PMID- 9639477
TI  - Sutureless cartilage graft laryngotracheal reconstruction using fibrin sealant.
AB  - OBJECTIVE: To determine whether fibrin sealant can replace suture as a means of
      holding a cartilage graft securely in the trachea. DESIGN: Randomized blinded
      control study comparing the use of fibrin sealant vs sutures in laryngotracheal
      reconstruction in ferrets. We compared results at 7 and 30 days. SUBJECTS: Forty
      ferrets randomized into 2 groups of 20: fibrin sealant and sutures. Within each
      group, half were studied at 7 days and the rest at 30 days. No ferrets were
      withdrawn from study because of adverse effects of the intervention.
      INTERVENTION: A carved costal cartilage graft was placed in the anterior cricoid
      split incision, and was secured with either fibrin sealant or sutures. All
      animals were extubated after recovery from anesthesia. Specimens were examined
      grossly and histologically. RESULTS: All animals survived until humanely killed.
      The pathologist, unaware of the groupings, measured lumen expansion in
      millimeters, cartilage graft migration, mucosal in-growth, degree of
      inflammation, graft integration, and graft viability. The fibrin sealant group
      had statistically significant (P<.05) better results in mucosal in-growth. In no
      categories was the suture group better than the fibrin sealant group. In
      comparing 7-day with 30-day results, the 30-day group had significantly better
      results in inflammation and graft viability. CONCLUSIONS: Fibrin sealant can be
      used in place of sutures with improvement in mucosal growth in costal cartilage
      laryngotracheal reconstruction in the experimental animal model. Use of fibrin
      sealant (instead of sutures) may result in less surgical trauma and edema, less
      surgical time, and faster recovery.

PMID- 9639478
TI  - Autogenous tissue-engineered cartilage: evaluation as an implant material.
AB  - OBJECTIVES: To determine whether autogenous tissue-engineered cartilage grafts
      can be synthesized in predetermined shapes, to compare tissue-engineered
      cartilage with native cartilage with respect to histological characteristics and
      biomechanical properties, and to demonstrate how multiple transplantations affect
      tissue-engineered cartilage. DESIGN: Controlled, prospective animal study.
      SUBJECTS: Twenty New Zealand white rabbits, 3 weeks old. INTERVENTIONS:
      Autogenous chondrocytes were seeded onto biodegradable polyglycolic acid-poly-L
      lactic acid copolymer templates in 1 of 3 shapes (cross, nasal tip graft, or
      auricle). Grafts and controls of sculpted cartilage were divided among 3 groups:
      short-term implantation (4 or 8 weeks), long-term implantation (6 or 12 months),
      and a reimplantation group. The gross morphological features, histological
      findings, and tensile strength of grafts were assessed. RESULTS: Production of
      tissue-engineered cartilage was confirmed in 30 of 31 implants. Histological
      evaluation demonstrated characteristic cartilaginous matrix, but with prominent
      vascular and fibrous tissue ingrowth. In long-term implantation grafts (n=4),
      foci of osteoid were evident by 6 months. In the subset of transplanted grafts
      (n=7), 5 of 7 demonstrated significant loss of cartilage viability. Tensile
      strength measurements demonstrated values 24% and 41% of those of controls at 4
      and 8 weeks, respectively. CONCLUSIONS: Tissue-engineered autogenous cartilage
      can be reliably produced, and predetermination of graft shape is possible.
      Histologically, grafts represent composites of mature cartilage infiltrated by
      vasculature and fibrous tissue, with delayed osteoid formation. Graft viability
      is compromised by early transplantation, and tensile strength is less than that
      of native cartilage. These results demonstrate the feasibility of tissue
      engineered cartilage as a future graft material.

PMID- 9639479
TI  - Chronic conductive hearing loss in adults: effects on the auditory brainstem
      response and masking-level difference.
AB  - OBJECTIVE: To determine whether chronic conductive hearing loss in adults results
      in changes in the auditory brainstem response (ABR) similar to those observed in
      children with histories of otitis media with effusion. DESIGN: Test of effect of
      unilateral conductive hearing loss on adult ABR using age-matched control group
      and subjects as their own controls. SUBJECTS: Twelve adults with a history of
      unilateral conductive ear disease. An age-matched control group of 21 adults was
      also tested. METHODS: The ABR, an electrophysiologic test of auditory brainstem
      functioning, was used to evaluate possible brainstem abnormalities in the
      impaired listeners. In addition, the masking-level difference, a behavioral test
      of binaural auditory processing in the brainstem, was used. RESULTS: When
      comparing the patients' diseased ears with their healthy ears, significant delays
      were seen for wave V as well as for the I-V and III-V interwave intervals. For
      comparison with the control population, significant prolongations were again seen
      for wave V and for the III-V interwave intervals. In addition, reduced masking
      level differences and significant correlations between the masking-level
      differences and the ABRs, independent of hearing threshold, were noted.
      CONCLUSIONS: The results suggest that chronic conductive impairment in adults
      leads to changes in the ABR similar to those observed in children with histories
      of otitis media with effusion. As such, these changes do not appear to be related
      to a critical period of development.

PMID- 9639480
TI  - Malignant infantile osteopetrosis: otolaryngological complications and
      management.
AB  - OBJECTIVES: To inform otolaryngologists about upper airway obstruction requiring
      tracheotomy and other otolaryngological manifestations of malignant infantile
      osteopetrosis (MIOP) and to discuss pathophysiological features, management, and
      new treatment strategies in MIOP. DESIGN: Ongoing case series combined with a
      retrospective chart review. SETTING: International tertiary pediatric hospital.
      INTERVENTIONS: Patients with MIOP were initially referred for treatment and
      routine follow-up. Tracheotomy was performed to manage obstructive sleep apnea.
      Audiograms were also performed at regular intervals. RESULTS: The records of 9
      patients were examined. The otolaryngological findings of hearing loss,
      obstructive sleep apnea (sometimes requiring tracheotomy), otitis media, and
      chronic osteomyelitis with facial fistulas were identified. CONCLUSIONS:
      Osteopetrosis is a rare condition caused by a failure of the osteoclast to resorb
      bone. This results in thickened dense, deformed, and easily fractured bone. As a
      result, growth failure, anemia, hypoplastic dentition, chronic infections, facial
      fistulas, blindness, hearing loss, nasal congestion, and upper airway obstruction
      may occur. The management of otolaryngological problems in a child with
      osteopetrosis is an important component in comprehensive care. To our knowledge,
      this study represents the largest case series of MIOP in the otolaryngology
      literature.

PMID- 9639481
TI  - Meniere disease caused by an anomalous vein of the vestibular aqueduct.
AB  - The precise cause of Meniere disease remains unclear. Multiple causes have been
      proposed with most experimental evidence pointing to impaired fluid resorption by
      the endolymphatic duct and sac as the final common pathway in development of
      hydrops. We report a unique case of Meniere disease secondary to compression of
      the endolymphatic duct and sac by an anomalous vein of the vestibular aqueduct.
      The resulting mechanical obstruction led to excessive accumulation of endolymph
      with clinical signs of Meniere disease. We review the literature and discuss
      proposed pathogenesis of disease. The finding of this anomalous vein provides
      further evidence that anatomical obstruction of the endolymphatic duct and sac
      may lead to Meniere-like symptoms. This unique example of an anatomical variant
      offers additional insight into the pathophysiology of endolymphatic hydrops.

PMID- 9639482
TI  - Further characterization of the DFNA1 audiovestibular phenotype.
AB  - BACKGROUND: Autosomal dominant, nonsyndromic, hereditary hearing impairment in a
      large Costa Rican kindred is caused by a mutation in the human homolog of the
      Drosophila diaphanous gene. OBJECTIVE: To further characterize the phenotype of
      DFNA1 with comprehensive audiovestibular evaluation and computed tomography of
      the temporal bone. PATIENTS: One affected child and 2 affected adults of the
      Costa Rican kindred who harbor a mutation in the diaphanous gene. SETTING:
      Medical Center at the University of California, San Francisco. INTERVENTION:
      Otologic and neuro-otologic examination; pure tone audiometry, speech audiometry,
      and immitance testing; auditory evoked potentials, electrocochleography, and
      otoacoustic emissions; electronystagmography and vestibular autorotation tests;
      and computed tomography of the temporal bone. RESULTS: The youngest subject, an 8
      year-old boy, had a mild hearing loss, intact stapedial reflexes, otoacoustic
      emissions at high frequencies, normal auditory evoked potentials, and
      electrocochleographic findings consistent with endolymphatic hydrops. The two
      adults had severe to profound bilateral sensorineural hearing impairment.
      Electronystagmography disclosed normal vestibular function. Computed tomography
      demonstrated normal external, middle, and inner ear structures. CONCLUSIONS:
      These results suggest that the early low-frequency hearing loss in this family is
      associated with endolymphatic hydrops. Elucidation of the role of the diaphanous
      gene in hearing will therefore lead to a better understanding of the mechanism of
      endolymphatic hydrops.

PMID- 9639483
TI  - Bilateral nasolacrimal duct obstruction managed with endoscopic techniques.
AB  - We present 3 cases of bilateral acquired nasolacrimal duct obstruction secondary
      to Wegener granulomatosis, sarcoidosis, and chronic lymphocytic leukemia. In all
      cases significant paranasal sinus and intranasal disease coincided with bilateral
      nasolacrimal duct obstruction. Surgical treatment of the nasolacrimal duct
      obstruction with dacryocystorhinostomy was more successful if the paranasal sinus
      disease was also treated. Nontraumatic bilateral nasolacrimal duct obstruction
      heralds unusual underlying systemic diseases, and coexisting paranasal sinus
      disease should be suspected. The simultaneous surgical treatment of both lacrimal
      and paranasal sinus disease through an endoscopic approach is advocated.

PMID- 9639484
TI  - Otolaryngological manifestations of Creutzfeldt-Jakob disease.
AB  - Creutzfeldt-Jakob disease (CJD) is one of the uniformly fatal spongiform
      encephalopathies that is characterized clinically by an unrelenting progression
      of myoclonus, dementia, and ataxia. Since many of these patients will develop
      cerebellar abnormalities, some may present to the otolaryngologist with
      dizziness. Hearing loss, however, to our knowledge, has not been reported. We
      describe a patient with CJD who presented with hearing loss and vague symptoms of
      imbalance, and whose disease progressed rapidly and fatally despite an extensive
      initial workup that was otherwise unrevealing. A review and discussion of the
      otolaryngological manifestations of CJD is presented. The otolaryngologist should
      be aware that CJD can present with otolaryngological manifestations, and with
      proper diagnosis extensive workups may be avoided.

PMID- 9639485
TI  - Minimal endoscopic approach.

PMID- 9639486
TI  - Pathologic quiz case 1. Salivary gland choristoma of the middle ear.

PMID- 9639487
TI  - Pathologic quiz case 2. Nasal leiomyosarcoma, low grade.

PMID- 9639488
TI  - Laser-assisted uvulopalatoplasty in mild obstructive sleep apnea.

PMID- 9639489
TI  - The success of LAUP in select patients with sleep-related breathing disorders.

PMID- 9639490
TI  - More data needed.

PMID- 9639491
TI  - Thrombopoietin and the hematopoietic stem cell.

PMID- 9639492
TI  - Role of c-mpl in early hematopoiesis.
AB  - Recently, several lines of evidence have indicated an expanded role for
      thrombopoietin (TPO) and its receptor, c-mpl, in hematopoiesis. In addition to
      being the primary physiological regulator of platelet production, it is now
      apparent that TPO also acts during early hematopoiesis. To futher define the role
      of TPO in early hematopoiesis we have identified discrete murine and human stem
      cell populations with respect to c-mpl expression and evaluated their potential
      for hematopoietic engraftment. Fluorescence-activated cell sorter analysis of
      enriched stem cell populations showed the presence of c-mpl expressing
      subpopulations. Approximately 50% of the murine fetal liver stem cell-enriched
      population, AA4(+)Sca+c-kit+, expressed c-mpl. Analysis of the murine marrow stem
      cell population LinloSca+c-kit+ showed that 70% of this population expressed c
      mpl. Expression of c-mpl was also detected within the human bone marrow
      CD34(+)CD38(-) stem cell progenitor pool and approximately 70% of that population
      expressed c-mpl. To rigorously evaluate the role of TPO/c-mpl in early
      hematopoiesis we compared the repopulation capacity of murine stem cell
      populations with respect to c-mpl expression in a competitive repopulation assay.
      When comparing the fetal liver progenitor populations, AA4(+)Sca+c-kit+c-mpl+ and
      AA4(+)Sca+c-kit+c-mpl-, we found that stem cell activity segregates with c-mpl
      expression. This result is complemented by the observation that the LinloSca+
      population of c-mpl gene-deficient mice was sevenfold less potent than LinloSca+
      cells from wild-type mice in repopulating activity. The engraftment potential of
      the human CD34(+)CD38(-)c-mpl+ population was evaluated in a severe combined
      immunodeficient-human bone model. In comparison to the CD34(+) CD38(-)c-mpl-
      population, the CD34(+)CD38(-)c-mpl+ cells showed significantly better
      engraftment. These results demonstrate a physiological role for TPO and its
      receptor, c-mpl, in regulating early hematopoiesis.

PMID- 9639493
TI  - Intracellular cytokine profile of cord and adult blood lymphocytes.
AB  - Umbilical cord blood (CB) transplantation is thought to be associated with a
      reduced risk of severe graft-versus-host-disease (GVHD) compared with bone marrow
      transplantation (BMT). The cytokine cascade is known to be important in the
      pathogenesis of GVHD; however, previous studies investigating the cytokine
      secretion pattern of CB cells have been contradictory because of variations in
      experimental techniques. In this study, the cytokine profile of cord and adult
      blood lymphocytes and lymphocyte subsets has been assessed at the single-cell
      level by flow cytometry, using CD4/CD8 and CD45RA/CD45RO markers. Cord and adult
      blood mononuclear cells were stimulated with phorbol 12-myristate 13-acetate
      (PMA) and ionomycin in the presence of monensin. After 4 to 24 hours of
      incubation, interleukin-2 (IL-2), IL-4, interferon-gamma (IFN-gamma), and tumor
      necrosis factor-alpha (TNF-alpha) production was measured by three-color flow
      cytometry. The results show that cord blood lymphocytes (CBL) produce less IL-2,
      IL-4, IFN-gamma, and TNF-alpha than adult peripheral blood lymphocytes (ABL).
      Further subset analysis showed that in CBL the majority of cytokine producing
      cells were CD4(+)CD45RA+, whereas in ABL the cytokine-producing cells were both
      CD4(+)CD45RO+ and CD8(+)CD45RO+. These results suggest that the reduced incidence
      of GVHD in CB transplantation may partly due to the altered cytokine profile seen
      in CBL.

PMID- 9639494
TI  - Antileukemic HLA-restricted T-cell clones generated with naturally processed
      peptides eluted from acute myeloblastic leukemia blasts.
AB  - Recent studies have shown that transfusions of HLA-compatible donor lymphocytes
      may induce complete remission in marrow-grafted patients with relapses of acute
      myeloblastic leukemia (AML). We investigated the in vitro generation of
      antileukemia T-cell clones obtained from the peripheral blood mononuclear cells
      of a partially HLA-compatible donor (HLA-A2 and B7 molecules in common with the
      leukemic blasts) after stimulation with a pool of naturally processed peptides
      extracted from leukemic blast cells collected at diagnosis from a patient with
      hyperleucocytosis AML. We recovered a significant quantity of peptides that bound
      to the HLA-A2 or HLA-B7 molecules that were able to induce cytolytic T-lymphocyte
      (CTL) lines and clones specific for the eluted AML peptides and restricted to the
      HLA-A2 or B7 molecules. Such CTL line did not recognize the patient's nonleukemic
      cells, and one clone was able to interact with the leukemic blasts from which the
      naturally processed peptides had been eluted. Such T-cell clones might provide a
      rationale for the development of adoptive immunotherapy and could be used to
      improve the efficiency of HLA-compatible T-lymphocyte transfusions and the graft
      versus-leukemia response in patients with AML.

PMID- 9639495
TI  - Protease-activated receptor genes are clustered on 5q13.
AB  - The serine protease, thrombin, is both a potent agonist for platelet aggregation
      and a mitogen inducing the proliferation of other cell types. Many cellular
      responses to thrombin are mediated by a G-protein-coupled thrombin receptor
      (protease-activated receptor-1, PAR-1). This represents the prototype of a new
      family of proteolytically cleaved receptors that includes PAR-2 and the recently
      identified PAR-3. Like PAR-1, PAR-3 is a potential thrombin receptor. Their
      similar gene structure, mechanism of activation, and colocalization to 5q13
      raises the question of a common evolutionary origin and of their belonging to a
      clustered gene family. Construction of a physical map of the 5q13 region by
      pulsed-field gel electrophoresis (PFGE) has allowed us to identify six potential
      CpG islands and to establish a linkage of the PAR genes. Southern blot analysis
      showed that they were in a cluster on a 560-kb Asc I fragment, in the order PAR
      2, PAR-1, and PAR-3. PAR-1 and PAR-2 genes were contained within the identical
      240-kb Not I fragment, thus confirming a tight linkage between them. The
      localization of other CpG islands suggested that more PAR-family genes may be
      present.

PMID- 9639496
TI  - Perturbed granulopoiesis in mice with a targeted mutation in the granulocyte
      colony-stimulating factor receptor gene associated with severe chronic
      neutropenia.
AB  - Mutations in the granulocyte colony-stimulating factor (G-CSF) receptor gene are
      found in a number of patients with severe chronic neutropenia predisposed to
      acute myeloid leukemia. These mutations result in the absence of the C-terminal
      domain of the G-CSF-R, a region which has been implicated in differentiation
      signaling. We generated mice with an equivalent mutation (gcsfr-triangle
      Delta715) by homologous and Cre-mediated recombination in embryonic stem cells.
      Both wt/triangle Delta715 and triangle Delta715/triangle Delta715 mice have
      significantly reduced numbers of blood neutrophils compared with their wt/wt
      littermates. However, under continuous G-CSF administration mutant mice develop
      peripheral neutrophil counts that significantly exceed those of wild-type
      littermates. These findings indicate that depending on G-CSF levels in mice, the
      triangle Delta715 mutation can contribute both to neutropenia and to
      neutrophilia.

PMID- 9639497
TI  - Prostaglandin E2 induces resistance to human immunodeficiency virus-1 infection
      in monocyte-derived macrophages: downregulation of CCR5 expression by cyclic
      adenosine monophosphate.
AB  - The chemokine receptor CCR5 can function as a coreceptor for human
      immunodeficiency virus-1 (HIV-1) entry into CD4(+) T cells and macrophages,
      especially during the early stages of HIV-1 infection. The regulation of CCR5
      expression may affect not only leukocyte migration, but also infectivity by HIV-1
      and, therefore, acquired immunodeficiency syndrome (AIDS) pathogenesis. We report
      here that agents which increase intracellular concentrations of cyclic adenosine
      monophosphate (cAMP) rapidly downregulate CCR5 gene expression, with consequent
      loss of CCR5 expression and function in monocytes/macrophages. Chemotaxis and
      intracellular Ca2+ mobilization in monocytes pretreated with prostaglandin E2 or
      dibutyryl-cAMP for 24 hours were significantly reduced in response to the CCR5
      ligand, MIP-1beta. Moreover, HIV-1 entry into monocyte-derived macrophages
      pretreated with dibutyryl-cAMP or prostaglandin E2 was markedly decreased. Our
      findings suggest that resistance to HIV-1 can be induced by agents which increase
      cellular levels of cAMP and that this may suggest additional therapeutic
      strategies to limit infection by HIV-1.

PMID- 9639498
TI  - Concentrations of thrombopoietin in bone marrow in normal subjects and in
      patients with idiopathic thrombocytopenic purpura, aplastic anemia, and essential
      thrombocythemia correlate with its mRNA expression of bone marrow stromal cells.
AB  - The function of bone marrow (BM) stromal thrombopoietin (TPO) in megakaryopoiesis
      remains unknown. In the present study we attempted to clarify the
      pathophysiological implications of stromal TPO in normal subjects (NS) and in
      patients with idiopathic thrombocytopenic purpura (ITP), aplastic anemia (AA),
      and essential thrombocythemia (ET) by measuring TPO concentrations in BM and
      peripheral blood (PB) and by estimating the levels of stromal TPO mRNA with
      TaqMan fluorescence-based post-reverse transcription-polymerase chain reaction
      product detection system. The results showed that TPO concentrations in PB were
      significantly elevated in patients with ITP (34.9 +/- 11.7 pg/mL) and AA (364.1
      +/- 153.5 pg/mL) but within normal range in patients with ET (each 20.0 and 22.1;
      NS, 22.1 +/- 8.2 pg/mL). In all subjects, the TPO concentrations in BM correlated
      well with the PB levels, and the former were consistently higher than the latter.
      The concentrations of TPO in BM also correlated with the levels of TPO mRNA in
      stromal cells. Furthermore, expression levels of TPO mRNA clearly correlated with
      megakaryocyte counts in NS and patients with ITP, indicating that stromal TPO
      actually enhances megakaryopoiesis. Thus, our results in the present study
      indicate that TPO from BM stromal cells is considered to play an essential role
      for megakaryopoiesis under various patho-physiological conditions.

PMID- 9639499
TI  - Detection and titration of human herpesvirus-8-specific antibodies in sera from
      blood donors, acquired immunodeficiency syndrome patients, and Kaposi's sarcoma
      patients using a whole virus enzyme-linked immunosorbent assay.
AB  - A human herpesvirus-8 (HHV-8) enzyme-linked immunosorbent assay (ELISA) with a
      whole virus lysate as antigen was developed and used to measure the
      seroprevalence rate and levels of IgG antibodies to HHV-8 in sera/plasma of
      various patient groups and blood donors. The virus antigen was prepared from the
      KS-1 cell line, which produces lytic virus, and therefore contains a broad array
      of viral proteins. Seroprevalence studies using this ELISA showed the following:
      10 of 91 blood donors (11%) had an average HHV-8 antibody titer of 118; 67 of 72
      (93%) classic Kaposi's sarcoma (KS) patients were positive with an average titer
      of 14,111; and 57 of 62 (92%) KS/human immunodeficiency virus (HIV) patients were
      positive with an average titer of 4,000. A study on a very limited number of
      serial serum samples from patients before and after diagnosis with KS showed
      highly elevated antibody titers to HHV-8 virus after KS lesions developed.
      Preliminary data show that 50% of the sera from HIV-1(+) homosexual patients
      contain IgG antibodies to HHV-8 suggesting that this population is at high risk
      for developing KS. Antibody results correlated well with the confirmatory
      immunofluorescent assays (IFA) using KS-1 cells as the substrate. This HHV-8 IgG
      antibody detection ELISA is sensitive and specific and does not cross-react with
      Epstein-Barr virus (EBV) or other human herpesviruses. The results of this HHV-8
      antibody survey suggest that this rapid ELISA assay can be used to screen large
      numbers of sera to find those at risk for developing KS.

PMID- 9639500
TI  - The redox state as a correlate of senescence and wasting and as a target for
      therapeutic intervention.
AB  - The loss of body cell mass (bcm) in senescence and wasting is poorly understood.
      We now show that the plasma cystine/acid soluble thiol ratio, ie, an indicator of
      the redox state, is increased in old age and cancer patients and correlated with
      a decrease in bcm and plasma albumin. A cause/effect relationship was suggested
      by two independent studies with N-acetyl-cysteine (NAC). NAC caused an increase
      in the bcm of healthy persons with high plasma cystine/thiol ratios, and
      treatment of cancer patients with NAC plus interleukin-2 caused an increase in
      bcm, plasma albumin, and functional capacity. Albumin levels below 680 micromol/L
      were associated with an increase in body water. Our studies suggest that the
      shift in the redox state may contribute to the loss of bcm and may provide a
      quantitative guideline for therapeutic intervention. Treatment of cancer patients
      with thiol-containing antioxidants may improve the quality of life.

PMID- 9639501
TI  - Treatment of anemia in myelodysplastic syndromes with granulocyte colony
      stimulating factor plus erythropoietin: results from a randomized phase II study
      and long-term follow-up of 71 patients.
AB  - Treatment with erythropoietin (epo) may improve the anemia of myelodysplastic
      syndromes (MDS) in approximately 20% of patients. Previous studies have suggested
      that treatment with the combination of granulocyte colony-stimulating factor (G
      CSF) and epo may increase this response rate. In the present phase II study,
      patients with MDS and anemia were randomized to treatment with G-CSF + epo
      according to one of two alternatives; arm A starting with G-CSF for 4 weeks
      followed by the combination for 12 weeks, and arm B starting with epo for 8 weeks
      followed by the combination for 10 weeks. Fifty evaluable patients (10 refractory
      anemia [RA], 13 refractory anemia with ring sideroblasts [RARS], and 27
      refractory anemia with excess blasts [RAEB]) were included in the study, three
      were evaluable only for epo as monotherapy and 47 for the combined treatment. The
      overall response rate to G-CSF + epo was 38%, which is identical to that in our
      previous study. The response rates for patients with RA, RARS, and RAEB were 20%,
      46%, and 37%, respectively. Response rates were identical in the two treatment
      groups indicating that an initial treatment with G-CSF was not neccessary for a
      response to the combination. Nine patients in arm B showed a response to the
      combined treatment, but only three of these responded to epo alone. This suggests
      a synergistic effect in vivo by G-CSF + epo. A long-term follow-up was made on 71
      evaluable patients from both the present and the preceding Scandinavian study on
      G-CSF + epo. Median survival was 26 months, and the overall risk of leukemic
      transformation during a median follow-up of 43 months was 28%. Twenty patients
      entered long-term maintenance treatment and showed a median duration of response
      of 24 months. The international prognostic scoring system (IPSS) was effective to
      predict survival, leukemic transformation, and to a lesser extent, duration of
      response, but had no impact on primary response rates.

PMID- 9639502
TI  - Prognostic significance of T-cell phenotype in aggressive non-Hodgkin's
      lymphomas. Groupe d'Etudes des Lymphomes de l'Adulte (GELA).
AB  - Peripheral T-cell lymphomas (PTCL) have been generally reported to have a worse
      prognosis than B-cell lymphomas (BCL). Because of their heterogeneity and
      scarcity, the outcomes of the different histological subtypes have not been
      compared. From October 1987 to March 1993, 1,883 patients with diffuse aggressive
      non-Hodgkin's lymphomas (NHL) included in the LNH87 protocol could be assessed
      for both morphology and immunophenotyping. Among them, 288 (15%) had PTCL and
      1,595 (85%) had BCL. According to the Kiel classification, most PTCL were
      classified as angioimmunoblastic (AIL; 23%), pleomorphic medium and large T-cell
      (PML; 49%), or anaplastic large cell (ALCL; 20%) lymphomas. Comparing PTCL with
      BCL patients, the former had more disseminated disease (78% v 58%), B symptoms
      (57% v 40%), bone marrow involvement (31% v 17%), skin involvement (21% v 4%),
      and increased beta2-microglobulin (50% v 34%), whereas BCL patients had more
      bulky disease (41% v 26%). According to the International Prognostic Index (IPI),
      PTCL and BCL scores were, respectively: 0 factors, 13% and 15%; 1 factor, 17% and
      22%; 2 factors, 24% and 25%; >/=3 factors, 45% and 37% (P = .09). For BCL and
      PTCL, respectively, complete remission rates were 63% and 54% (P = .004); the 5
      year overall survival (OS) rates were 53% and 41% (P = .0004) and event-free
      survival (EFS) rates were 42% and 33% (P < . 0001). Comparison of the different
      histological subtypes of lymphoma showed that the 5-year OS rate for T-ALCL (64%)
      was superior to those of other PTCL (35%) as well as diffuse large B-cell (53%)
      NHL. When multivariate analysis was applied using the IPI score as one factor,
      nonanaplastic PTCL remained an independent parameter (P = . 0004). Although the
      poor prognosis of non-ALCL PTCL could be due in part to the presence of adverse
      prognostic factors at diagnosis, this study shows that the T-cell phenotype is an
      independent significant factor, which should be incorporated into the definition
      of prognostic groups.

PMID- 9639503
TI  - Sustained gene expression in retrovirally transduced, engrafting human
      hematopoietic stem cells and their lympho-myeloid progeny.
AB  - Inefficient retroviral-mediated gene transfer to human hematopoietic stem cells
      (HSC) and insufficient gene expression in progeny cells derived from transduced
      HSC are two major problems associated with HSC-based gene therapy. In this study
      we evaluated the ability of a murine stem cell virus (MSCV)-based retroviral
      vector carrying the low-affinity human nerve growth factor receptor (NGFR) gene
      as reporter to maintain gene expression in transduced human hematopoietic cells.
      CD34(+) cells lacking lineage differentiation markers (CD34(+)Lin-) isolated from
      human bone marrow and mobilized peripheral blood were transduced using an
      optimized clinically applicable protocol. Under the conditions used, greater than
      75% of the CD34(+) cell population retained the Lin- phenotype after 4 days in
      culture and at least 30% of these expressed a high level of NGFR (NGFR+) as
      assessed by fluorescence-activated cell sorter analysis. When these CD34(+)Lin
      NGFR+ cells sorted 2 days posttransduction were assayed in vitro in clonogenic
      and long-term stromal cultures, sustained reporter expression was observed in
      differentiated erythroid and myeloid cells derived from transduced progenitors,
      and in differentiated B-lineage cells after 6 weeks. Moreover, when these
      transduced CD34(+)Lin-NGFR+ cells were used to repopulate human bone grafts
      implanted in severe combined immunodeficient mice, MSCV-directed NGFR expression
      could be detected on 37% +/- 6% (n = 5) of the donor-type human cells recovered 9
      weeks postinjection. These findings suggest potential utility of the MSCV
      retroviral vector in the development of effective therapies involving gene
      modified HSC.

PMID- 9639504
TI  - Interleukin-7 influences the development of thymic dendritic cells.
AB  - Interleukin-7 (IL-7) has been shown to be a critical factor in B and T
      lymphopoiesis, and to influence the differentiation of myeloid cell lineages. In
      the present study we extend these results demonstrating that IL-7 also plays an
      important role in the development of thymic dendritic cells (DC). The addition of
      IL-7 to rat fetal thymus organ cultures (FTOC) resulted in a drastic increase in
      the number of CD3(-)CD4(-)CD8(-) cells, which mostly expressed typical DC
      markers, including major histocompatibility complex class II, OX-62, CD11b, CD68,
      and CD54. These cells exhibited morphological and ultrastructural features of DC,
      and were potent stimulators of the allogeneic mixed leukocyte reaction. Although
      increased numbers of DC were continuously generated throughout the culture period
      in the presence of IL-7, they were not actively dividing, indicating that DC in
      IL-7-treated cultures did not arise by expansion of pre-existing cells. Reduced
      DC numbers obtained after the addition of neutralizing anti-IL-7 antibodies to
      mouse FTOC confirmed the relevance of endogenously produced IL-7 on thymic DC
      development. Furthermore, the addition of IL-7 to FTOC derived from severe
      combined immunodeficient mice also generated large numbers of DC in the absence
      of thymocyte maturation.

PMID- 9639505
TI  - Involvement of Fas-mediated apoptosis in the hematopoietic progenitor cells of
      graft-versus-host reaction-associated myelosuppression.
AB  - The influence of graft-versus-host (GVH) reaction on the host hematopoietic cells
      clinically manifests itself both as adverse reactions in transfusion-associated
      GVH disease (GVHD) and as a therapeutic graft-versus-leukemia (GVL) effect in
      either donor lymphocytes transfusion (DLT) or allogeneic bone marrow (BM)
      transplantation. We examined the effect of GVH reaction on the host hematopoiesis
      in the murine parent-into-F1 (P1 --> F1) model of GVHD. The systemic transfer of
      5 x 10(7) of C57BL/6 (B6) splenocytes into (B6xDBA/2)F1 mice (BDF1), which
      results in acute GVHD, reduced the peripheral blood cell counts, the number of BM
      cells, and colony-forming unit-granulocyte macrophage (CFU-GM), whereas the
      injection of 10(8) of DBA/2 cells into BDF1, which results in chronic GVHD, did
      not affect hematopoiesis 2 weeks after the transfer. To clarify the mechanism of
      such myelosuppression, we examined the Fas expression in both hematopoietic
      progenitor cells as well as whole BM cells. The Fas expressions in each fraction
      significantly increased in BDF1 mice 2 weeks after the induction of acute GVHD,
      whereas no such effects were observed in the BDF1 mice with chronic GVHD.
      Furthermore, when such BM cells were incubated with anti-Fas antibody (Jo2),
      which induces apoptosis through Fas, the fraction of apoptotic cells increased
      and the number of CFU-GM decreased significantly. The in vivo administration of
      neutralizing anti-FasL antibody into BDF1 mice receiving with B6 spleen cells
      thus protected the host mice from BM failure. These results indicate that the
      functional expression of Fas on hematopoietic cells plays an essential role in
      the myelosuppressive effect of GVHD.

PMID- 9639506
TI  - Growth disturbance in fetal liver hematopoiesis of Mll-mutant mice.
AB  - The MLL (ALL-1, HRX) gene is frequently involved in chromosomal translocations in
      acute leukemia and has homology with Drosophila trithorax, which controls
      homeobox gene expression and embryogenesis. To elucidate the function of Mll, we
      generated mice with a mutated Mll locus. Mice with a homozygous mutation were
      embryonic lethal and died at embryonic day 11.5 to 14.5, showing edematous bodies
      and petechiae. Histological examination revealed that hematopoietic cells were
      decreased in the liver of homozygous embryos, although they were composed of
      erythroid, myeloid, monocytic, and megakaryocytic cells with normal
      differentiation. Colony-forming assays using cells from fetal livers and yolk
      sacs showed that the number of colonies was markedly reduced and many of the
      colonies delayed to be recognized in Mllmu/mu embryos, although some of the
      colonies from Mllmu/mu embryos developed similarly with that from Mll+/+ and
      Mll+/mu embryos, suggesting the delayed onset of the proliferation of
      hematopoitic precursors. These data show that the hematopoietic precursors were
      greatly reduced in mutant mice, and suggest that Mll functions as a regulator of
      the growth of hematopoietic precursors.

PMID- 9639507
TI  - Bifurcated dendritic cell differentiation in vitro from murine lineage phenotype
      negative c-kit+ bone marrow hematopoietic progenitor cells.
AB  - We have recently established the culture system to generate dendritic cells (DCs)
      from murine Lin-c-kit+ bone marrow hematopoietic progenitor cells (HPCs) in the
      presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) + stem cell
      factor (SCF) + tumor necrosis factor-alpha (TNF-alpha). We present here the
      identification of two DC precursor subsets originated from HPCs with the
      phenotype of CD11b-/dullCD11c+ and CD11b+hiCD11c+ that develop independently at
      early time points (days 4 to 6) in the same culture conditions. Both of CD11b
      /dullCD11c+ and CD11b+hiCD11c+ precursors could differentiate at day 10 to 14
      into CD11b-/dullCD11c+ mature DCs with typical morphology, phenotype, and the
      ability to stimulate allogenic mixed leukocyte reaction (MLR). However, the
      endocytic capacity of fluorescein isothiocyanate-dextran was markedly reduced
      during the differentiation. CD11b-/dullCD11c+ precursors expressed high levels of
      Ia, CD86, CD40, and E-cadherin molecules, but not c-fms transcript, and mature
      DCs derived from this precursor subset continue to express abundant E-cadherin
      antigen, a discernible marker for Langerhans cells. In contrast, CD11b+hiCD11c+
      precursors expressed c-fms mRNA, but low levels of Ia, CD86, and E-cadherin,
      whereas CD40 was undetectable. CD11b-/dullCD11c+ mature DCs differentiated from
      these precursors displayed abundant c-fms mRNA and nonspecific esterase activity.
      Interestingly, CD11b+hiCD11c+ precursors, but not CD11b-/dullCD11c+ precursors,
      may be bipotent cells that can be induced by M-CSF to differentiate into
      macrophages. All of these results suggest that CD11b-/dullCD11c+ and
      CD11b+hiCD11c+ cells are distinct DC precursors derived from Lin-c-kit+ HPCs,
      which differentiate into mature DCs through bifurcated and independent DC
      differentiation pathways.

PMID- 9639508
TI  - Induction of synaptosomal-associated protein-23 kD (SNAP-23) by various
      cytokines.
AB  - Cytokines manifest their function through regulation of gene expression. We
      searched for immediate-early cytokine responsive genes by the mRNA differential
      display technique using interleukin-3 (IL-3)-dependent OTT-1 cells, and have
      isolated a novel cDNA which encodes 210 amino acids and shows 87% amino acid
      identity to human SNAP-23 (synaptosomal-associated protein of 23 kD). The message
      for this protein (mouse SNAP-23) was induced in OTT-1 cells by IL-3, granulocyte
      macrophage colony-stimulating factor (GM-CSF), and IL-5. The experiment using C
      terminal deletion mutants of the common beta subunit (betac) of IL-3/GM-CSF/IL-5
      receptors showed that expression of SNAP-23 was associated with the Ras-Raf-MAPK
      pathway, but not with the JAK-STAT pathway. Moreover, SNAP-23 was induced in
      response to a wide variety of cytokines, including IL-2, IL-3, IL-5, IL-10, stem
      cell factor, G-CSF, GM-CSF, leukemia inhibitory factor, and erythropoietin.
      Constitutive expression of SNAP-23 was seen in various tissues, including heart,
      lung, kidney, liver, spleen, and small intestine. Possible involvement of SNAP-23
      in cytokine signal transduction is discussed.

PMID- 9639509
TI  - Some human inhibitor antibodies interfere with factor VIII binding to factor IX.
AB  - Factor VIII (fVIII) functions as a cofactor of factor IXa in the intrinsic
      pathway of blood coagulation. Its absence or abnormality causes the bleeding
      disorder hemophilia A. About 23% of hemophiliacs who receive therapeutic fVIII
      infusions develop antibodies that inhibit its activity. We previously showed by
      inhibitor neutralization assays that the fVIII A2 and C2 domain polypeptides
      contain common inhibitor epitopes. Often hemophilic inhibitor plasmas were
      partially neutralized by C2 and more completely neutralized by fVIII light chain
      (A3-C1-C2), suggesting the presence of an additional major inhibitor epitope(s)
      within the A3-C1 domains. In immunoprecipitation assays, 17 of 18 inhibitor IgGs
      bound to recombinant 35S-A3-C1. Amino acids 1811-1818 of the A3 domain comprise a
      binding site for factors IX and IXa. Three inhibitor IgGs prevented binding of
      factor IXa to fVIII light chain, and the binding of each IgG to light chain was
      competed by A3 peptide 1804-1819. The generation of factor Xa by the fVIIIa/fIXa
      complex in a chromogenic assay was prevented by these inhibitors. Therefore, we
      propose that another important mechanism of fVIII inactivation by human
      inhibitors is the prevention of fVIIIa/fIXa association.

PMID- 9639510
TI  - Cancer procoagulant and tissue factor are differently modulated by all-trans
      retinoic acid in acute promyelocytic leukemia cells.
AB  - All-trans-retinoic acid (ATRA) downregulates the expression of two cellular
      procoagulants, tissue factor (TF) and cancer procoagulant (CP), in human
      promyelocytic leukemia cells. To evaluate whether or not changes of the
      procoagulant activities (PCAs) may share mechanisms with the ATRA-induced cyto
      differentiation process, we have characterized the effect of ATRA on the TF and
      CP expression by NB4 cells, an ATRA maturation-inducible cell line, and two NB4
      derived cell lines resistant to ATRA-induced maturation, the NB4. 306 and
      NB4.007/6 cells. Next, we evaluated the effect on the PCAs of the NB4 parental
      cells of three synthetic retinoid analogues, ie: AM580 (selective for the
      retinoic acid receptor [RAR] alpha), capable to induce the granulocytic
      differentiation of NB4 cells; and CD2019 (selective for RARbeta) and CD437
      (selective for RARgamma), both lacking this capability. Cells were treated with
      either ATRA or the analogues (10(-6) to 10(-8) mol/L) for 96 hours. The effect on
      cell differentiation was evaluated by morphologic changes, cell proliferation,
      nitro blue tetrazolium reduction assay, and flow cytometry analysis of the CD33
      and CD11b surface-antigen expression. PCA was first measured in 20 mmol/L Veronal
      Buffer cell extracts by the one-stage clotting assay of normal and FVII-deficient
      plasmas. Further TF and CP have been characterized and quantified in cell-sample
      preparations by chromogenic and immunological assays. In the first series of
      experiments, ATRA downregulates both TF and CP in NB4 parental cells, as
      expected. However, in the differentiation-resistant cell lines, it induced a
      significant loss of TF but had little or no effect on CP. In a second series of
      experiments, in the NB4 parental cells, the RARalpha agonist (AM580) induced cell
      maturation and reduced 91% CP expression, whereas CD437 and CD2019 had no cyto
      differentiating effects and did not affect CP levels. On the other hand, in the
      same cells the TF expression was reduced by ATRA and AM580, but also by the
      RARbeta agonist CD2019, which did not induce cell maturation. These data indicate
      that in NB4 cells, ATRA modulation of CP occurs in parallel with signs of cell
      differentiation, while the regulation of TF appears to be at least in part
      independent from these processes, and involves both alpha and beta nuclear
      retinoid receptors.

PMID- 9639511
TI  - The P2Y1 receptor is necessary for adenosine 5'-diphosphate-induced platelet
      aggregation.
AB  - The human P2Y1 receptor heterologously expressed in Jurkat cells behaves as a
      specific adenosine 5'-diphosphate (ADP) receptor at which purified adenosine
      triphosphate (ATP) is an ineffective agonist, but competitively antagonizes the
      action of ADP. This receptor is thus a good candidate to be the elusive platelet
      P2T receptor for ADP. In the present work, we examined the effects on ADP-induced
      platelet responses of two selective and competitive P2Y1 antagonists, adenosine
      2'-phosphate-5'-phosphate (A2P5P) and adenosine-3'-phosphate-5'-phosphate
      (A3P5P). Results were compared with those for the native P2Y1 receptor expressed
      on the B10 clone of rat brain capillary endothelial cells (BCEC) and for the
      cloned human P2Y1 receptor expressed on Jurkat cells. A2P5P and A3P5P inhibited
      ADP-induced platelet shape change and aggregation (pA2 = 5) and competitively
      antagonized calcium movements in response to ADP in fura-2-loaded platelets, B10
      cells, and P2Y1-Jurkat cells. In contrast, these compounds had no effect on ADP
      induced inhibition of adenylyl cyclase in platelets or B10 cells, whereas known
      antagonists of platelet activation by ADP such as Sp-ATPalphaS were effective.
      These identical signaling responses and pharmacologic properties suggest that
      platelets and BCEC share a common P2Y1 receptor involved in ADP-induced
      aggregation and vasodilation, respectively. This P2Y1 receptor coupled to the
      mobilization of intracellular calcium stores was found to be necessary to trigger
      ADP-induced platelet aggregation. The present results, together with data from
      the literature, also point to the existence of another as yet unidentified ADP
      receptor, coupled to adenylyl cyclase and responsible for completion of the
      aggregation response. Thus, the term, P2T, should no longer be used to designate
      a specific molecular entity.

PMID- 9639512
TI  - Anticoagulant effects of 1alpha,25-dihydroxyvitamin D3 on human myelogenous
      leukemia cells and monocytes.
AB  - The hormonally active form of vitamin D is 1alpha, 25-dihydroxyvitamin D3
      [1,25(OH)2D3], which is a principal regulator of calcium homeostasis. It also
      affects hormone secretion, cell differentiation, and proliferation by a mode of
      action that involves stereospecific interaction with an intracellular vitamin D
      receptor (VDR). We recently found that retinoids, which are vitamin A
      derivatives, exert anticoagulant effects by upregulating thrombomodulin (TM) and
      downregulating tissue factor (TF) expression in acute promyelocytic leukemia
      cells and monoblastic leukemia cells. Both the VDR and retinoid receptors belong
      to the same family of receptors. A heterodimer consisting of the retinoid X
      receptor and the VDR binds to vitamin D responsive elements on genes regulated by
      vitamin D. To determine whether 1,25(OH)2D3 would exhibit anticoagulant effects
      similar to retinoids, we measured the antigen level, activity, and mRNA level of
      TM and TF in human leukemic cells, vascular endothelial cells, and monocytes
      treated with 1,25(OH)2D3. We found that 1,25(OH)2D3 upregulates antigen
      expression, activity, and mRNA levels of TM and downregulates antigen expression,
      activity, and mRNA levels of TF in human monocytic leukemia cells, some acute
      myelogenous leukemia cells, and monocytes, but not in umbilical vein endothelial
      cells. Transient transfection studies with reporter plasmids in monocytic
      leukemia cells and mobility gel-shift assay showed interaction with 1,25(OH)2D3
      and functional retinoic acid responsive elements present in the 5'-flanking
      region of the TM gene. However, auxiliary factors or other elements in the TM
      gene may contribute to VDR specificity and transactivation of the gene in
      specific target cells. These findings indicate that 1,25(OH)2D3 resembles the
      retinoids in its control of the transcription of the TM and TF genes in human
      monocytic cells. Analogs of 1,25(OH)2D3 with anticoagulant activity may serve as
      adjunctive antithrombotic agents in monocytic leukemia and atherosclerotic
      disease.

PMID- 9639513
TI  - Targeted inactivation of the coagulation factor IX gene causes hemophilia B in
      mice.
AB  - Hemophilia B is a leading target for gene therapy because current therapy is not
      optimal. Hence, a murine model of factor IX (F. IX) deficiency was generated to
      develop gene therapy strategies for hemophilia B. A targeting vector was created
      by replacing a 3.2-kb segment of the gene encompassing the catalytic domain with
      a phosphoglycerokinase promoter-driven neomycin resistant (neor) gene cassette.
      The transfected embryonic stem cell clones generated chimeric male mice, and germ
      line transmission of the inactivated F. IX gene was observed in their offsprings.
      Southern analysis confirmed the mutant genotype in hemizygous male and carrier
      female mice. F. IX transcripts were not detected in liver RNA isolated from
      hemizygous mice, and lower levels of F. IX mRNA were noted in carrier female mice
      when compared with those of normal litter mates. As expected, the mean F. IX
      coagulant titer of affected male mice was 2.8 U/dL (n = 10), while the mean F. IX
      titer of carrier female mice was 35 U/dL (n = 14), compared with 69 U/dL (n = 9)
      for the normal female mice and 92 U/dL (n = 22) for normal male and female litter
      mates. Further, the tail bleeding time of hemizygous mice was markedly prolonged
      (>3 hours) compared with those of normal and carrier female litter mates (15 to
      20 minutes). Seven of 19 affected male mice died of exsanguination after tail
      snipping, and two affected mice died of umbilical cord bleeding. Currently, there
      are 10 affected mice surviving at 4 months of age. Aside from the factor IX
      defect, the carrier female and hemizygous male mice had no liver pathology by
      histologic examination, were fertile, and transmitted the F. IX gene mutation in
      the expected Mendelian frequency. Taken together, we have generated a F. IX
      knockout mouse for evaluation of novel gene therapy strategies for hemophilia B.

PMID- 9639514
TI  - Naturally occurring mutations in glycoprotein Ibalpha that result in defective
      ligand binding and synthesis of a truncated protein.
AB  - The platelet GPIb-V-IX complex is the receptor for the initial binding of von
      Willebrand factor (vWF) mediating platelet adhesion. The complex is composed of
      four membrane-spanning glycoproteins (GP): GPIbalpha, GPIbbeta, GPIX, and GPV.
      Bernard-Soulier syndrome results from a qualitative or quantitative defect in one
      or more components of the platelet membrane GPIb-V-IX complex. We describe the
      molecular basis of a novel Bernard-Soulier syndrome variant in two siblings in
      whom GPIbalpha was not detected on the platelet surface but that was present in a
      soluble form in plasma. DNA sequence analysis showed that the affected
      individuals were compound heterozygotes for two mutations. One, inherited from a
      maternal allele, a T777 --> C point mutation in GPIbalpha converting Cys65 -->
      Arg within the second leucine rich repeat, the other, a single nucleotide
      substitution (G2078 --> A) for the tryptophan codon (TGG) causing a nonsense
      codon (TGA) at residue 498 within the transmembrane region of GPIbalpha,
      inherited from a mutant paternal allele. The Bernard-Soulier phenotype was
      observed in siblings who were compound heterozygotes for these two mutations.
      Although GPIbalpha was not detected on the surface of the patient's platelets,
      soluble GPIbalpha could be immunoprecipitated from plasma. When plasmids encoding
      GPIbalpha containing the Cys65 --> Arg mutation were transiently transfected into
      Chinese hamster ovary (CHO) cells stably expressing the GPbeta-IX complex
      (CHObetaIX), the expression of GPIbalpha was similar to the wild-type (WT)
      GPIbalpha, but did not bind vWF. When plasmids encoding GPIbalpha containing the
      Trp498 --> stop were transiently transfected into CHObetaIX, the surface
      expression of GPIbalpha was barely detectable compared with the WT GPIbalpha.
      Thus, this newly described compound heterozygous defect produces Bernard-Soulier
      syndrome by a combination of synthesis of a nonfunctional protein and of a
      truncated protein that fails to insert into the platelet membrane and is found
      circulating in plasma.

PMID- 9639515
TI  - Construction and characterization of a fusion protein of single-chain anti-CD20
      antibody and human beta-glucuronidase for antibody-directed enzyme prodrug
      therapy.
AB  - The CD20 antigen is an attractive target for specific treatment of B-cell
      lymphoma. Antibody-directed enzyme prodrug therapy (ADEPT) aims at the specific
      activation of a nontoxic prodrug at the tumor site by an enzyme targeted by a
      tumor-specific antibody such as anti-CD20. We constructed a fusion protein of the
      single-chain Fv anti-CD20 mouse monoclonal antibody (MoAb) 1H4 and human beta
      glucuronidase for the activation of the nontoxic prodrug N-[4-doxorubicin-N
      carbonyl(-oxymethyl) phenyl] O-beta-glucuronyl carbamate to doxorubicin at the
      tumor site. The cDNAs encoding the light- and heavy-chain variable regions of 1H4
      were cloned, joined by a synthetic sequence encoding a 15-amino acid linker and
      fused to human beta-glucuronidase by a synthetic sequence encoding a 6-amino acid
      linker. An antibody-enzyme fusion protein-producing cell line was established by
      transfection of the construct into human embryonic kidney 293/EBNA cells. The
      yield of active fusion protein was 100 ng/mL transfectoma supernatant. Antibody
      affinity, antibody specificity, and enzyme activity were fully retained by the
      fusion protein. Immunoprecipitation and analysis by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) showed that the fusion protein has
      a relative molecular weight (Mw) of 100 kD under denaturing conditions. Gel
      filtration analysis indicated that the enzymatically active form of the fusion
      protein is a tetramer with an Mw of approximately 400 kD. The nontoxic prodrug N
      [4-doxorubicin-N-carbonyl(-oxymethyl) phenyl] O-beta-glucuronyl carbamate was
      hydrolyzed by the fusion protein at a hydrolysis rate similar to that of human
      beta-glucuronidase. When the fusion protein was specifically bound to Daudi
      lymphoma cells, the prodrug induced similar antiproliferative effects as
      doxorubicin. Thus, it is feasible to construct a eukaryotic fusion protein
      consisting of a single-chain anti-CD20 antibody and human beta-glucuronidase for
      future use in the activation of anticancer prodrugs in B-cell lymphoma.

PMID- 9639516
TI  - Localization of receptors for vasoactive intestinal peptide, somatostatin, and
      substance P in distinct compartments of human lymphoid organs.
AB  - Regulatory peptides, such as vasoactive intestinal peptide (VIP), somatostatin
      (SS), or substance P (SP), are considered to play a role in immune regulation. To
      localize the targets of these peptides in the human immune system, their
      receptors have been evaluated with in vitro receptor autoradiography in lymph
      nodes, tonsils, appendix, Peyer's patches, spleen, and thymus. The three peptide
      receptors were detected in all lymphoid tissues tested, but, unexpectedly,
      usually in distinct compartments. In lymph nodes, palatine tonsils, vermiform
      appendix, and Peyer's patches, VIP receptors were found in the CD3 positive zone
      around lymphoid follicles; SS receptors in the germinal centers of secondary
      follicles; and SP receptors mainly in interfollicular blood vessels. In the
      spleen, VIP receptors were detected in periarterial lymphatic sheaths, SS
      receptors in the red pulp, and SP receptors in the central arteries. In the
      thymus, VIP receptors were present in cortex and medulla, SS receptors in the
      medulla, and SP receptors in blood vessels. For comparison, cholecystokinin (CCK)
      A and -B receptors were not demonstrated in any of these tissues. These results
      suggest a strong compartmentalization of the three peptide receptors in human
      lymphoid tissues and represent the molecular basis for the understanding of a
      very complex and interactive mode of action of these peptides.

PMID- 9639517
TI  - Expression of the CD8alpha beta-heterodimer on CD8(+) T lymphocytes in peripheral
      blood lymphocytes of human immunodeficiency virus- and human immunodeficiency
      virus+ individuals.
AB  - CD8(+) T lymphocytes play a pivotal role in controlling human immunodeficiency
      virus (HIV)-1 replication in vivo. We have performed four-color flow cytometric
      analysis of CD8(+) peripheral blood lymphocytes (PBL) from 21 HIV-1 seronegative
      and 103 seropositive individuals to explore the phenotypic heterogeneity of
      CD8beta-chain expression on CD8(+) T lymphocytes and to clarify how its
      expression on CD8(+) T lymphocytes may relate to acquired immunodeficiency
      syndrome (AIDS) clinical progression. We showed that the single monoclonal
      antibody (MoAb) 2ST8-5H7, directed against the CD8alpha beta-heterodimer,
      identifies CD8(+) T lymphocytes as effectively as the conventional combination of
      anti-CD3 and anti-CD8alpha antibodies. However, we detected a significantly lower
      mean fluorescence (MF) of anti-CD8alpha beta staining on PBL from HIV-1
      seropositive donors as compared with seronegative donors. In fact, CD8(+) T
      lymphocytes from HIV-1-infected individuals with the lowest CD4 counts showed the
      lowest levels of CD8alpha beta MF. To explore further this change in CD8alpha
      beta expression, we assessed the expression of 14 different cell surface
      molecules on CD8alpha beta+ T lymphocytes of PBL from 11 HIV-1 seronegative and
      22 HIV-1 seropositive individuals. The MF of anti-CD8alpha beta staining was
      significantly reduced on CD8(+) T lymphocyte subsets that showed immunophenotypic
      evidence of activation. The subset of lymphocytes expressing low levels of
      CD8alpha beta expressed higher levels of activation, adhesion, and cytotoxic
      associated molecules and was predominantly CD45RO+ and CD28(-). Finally, we
      monitored the expression of the CD8alpha beta-heterodimer on PBL of eight HIV-1
      infected individuals over a 16-week period after the initiation of highly active
      antiretroviral therapy (HAART), including zidovudine (ZDV), lamivudine (3TC), and
      indinavir (IDV), and found a significant increase in the expression of the
      CD8alpha beta-heterodimer. These results suggest that antibodies recognizing the
      CD8alpha beta-heterodimer are useful tools to specifically identify CD8(+) T
      lymphocytes. Moreover, the quantitative monitoring of CD8alpha beta expression
      allows the detection of discrete CD8(+) T lymphocyte subsets and may be useful
      for assessing the immune status of individuals infected with HIV-1.

PMID- 9639518
TI  - Adhesion, transendothelial migration, and reverse transmigration of in vitro
      cultured dendritic cells.
AB  - Dendritic cells (DC) are migratory cells which exhibit complex trafficking
      properties in vivo, involving interaction with vascular and lymphatic endothelium
      and extracellular matrix (ECM). The underlying mechanisms involved in these
      processes are still ill defined. In the present study we have investigated the
      ability of DC to interact in vitro with human vascular endothelial cells (EC) and
      ECM. DC were differentiated from monocytes by in vitro exposure to granulocyte
      macrophage colony-stimulating factor and interleukin-13 for 7 days. In adhesion
      assays a considerable proportion of DC bound to resting EC monolayers: (17% +/-
      4%, mean +/- SE of eight experiments). Adhesion to tumor necrosis factor (TNF)
      activated EC was increased to 29% +/- 5% (n = 8). Binding to resting EC was
      strongly inhibited by anti-CD11a and CD11b, but not by CD11c monoclonal
      antibodies (MoAbs); on TNF-activated EC, anti-VLA-4 in concert with anti-CD18
      inhibited adhesion by more than 70%. Binding to a natural ECM, derived from
      cultured EC, or to purified fibronectin was high: 52% +/- 6% (n = 8) involved VLA
      4 and VLA-5 integrins. In a transmigration assay, 10% +/- 2% (n = 6) of input
      cells were able to cross the EC monolayer. Unlike adhesion, transendothelial
      migration was significantly reduced by anti-CD31 MoAb. The amount of DC
      transmigrated through a monolayer of EC was increased twofold to threefold by a
      defined set of C-C chemokines including RANTES, MIP1alpha, MIP5, and, to a lesser
      extent, by MIP1beta and MCP-3. Most importantly, in view of the trafficking
      pattern of these cells, a significant proportion of DC (13% +/- 4% of input cells
      seeded) was able to migrate across the endothelial basement membrane and,
      subsequently, across the endothelial barrier (reverse transmigration). The
      adhesion molecules and chemoattractants characterized herein are likely to
      underlie the complex trafficking of DC in vivo.

PMID- 9639519
TI  - Production of interleukin-10 by granulocyte colony-stimulating factor-mobilized
      blood products: a mechanism for monocyte-mediated suppression of T-cell
      proliferation.
AB  - Previous reports showed that granulocyte colony-stimulating factor (G-CSF)
      mobilized peripheral blood mononuclear cells (G-PBMC) are hyporesponsive to
      alloantigen compared with control PBMC. In the current study, neutralizing
      antibodies to interleukin-10 (IL-10) increased the proliferative response of G
      PBMC to alloantigen by 50. 14% (+/- 12.79%; n = 8), whereas the proliferative
      response of control PBMC was not affected. The inhibition of OKT3-stimulated CD4
      cell proliferation by G-PBMC-derived CD14(+) cells could also be abrogated by the
      addition of IL-10 neutralizing antibodies. Further, IL-10 levels correlated with
      the number of CD14 cells in these cultures. Constitutive IL-10 mRNA levels
      detected by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR)
      were 10-fold higher in G-PBMC compared with control PBMC. This translated into
      significantly higher IL-10 levels after 24-hour lipopolysaccharide (LPS)
      stimulation of G-PBMC compared with control PBMC (P = .036). IL-10 mRNA levels
      were also fivefold higher in isolated G-PBMC-derived CD14 cells compared with
      control CD14 cells. This corresponded to increased constitutive production of IL
      10 by isolated G-PBMC-derived CD14 cells compared with control CD14 cells (357.2
      +/- 104.5 v 51.7 +/- 30.5, P = .051). In conclusion, these data suggest that
      monocytes contained within G-PBMC, which, in comparison to marrow, are increased
      in absolute number and relative proportion to T cells, may suppress T-cell
      responsiveness by secretion of IL-10.

PMID- 9639521
TI  - Microsatellite instability and frameshift mutations in BAX and transforming
      growth factor-beta RII genes are very uncommon in acute lymphoblastic leukemia in
      vivo but not in cell lines.
AB  - Mutations in the DNA mismatch repair (MMR) system lead to an instability of
      simple repetitive DNA sequences involved in several cancer types. This
      instability is reflected in a high mutation rate of microsatellites, and recent
      studies in colon cancer indicate that defects in MMR result in frequent
      frameshift mutations in mononucleotide repeats located in the coding regions of
      BAX and transforming growth factor-beta (TGF-beta) receptor genes. Circumstantial
      evidence suggests that the MMR defect may be involved in some lymphoid
      malignancies, although several allelotype analyses have concluded on the low
      level of microsatellite instability in acute lymphoblastic leukemias. To further
      evaluate the implication of MMR defects in leukemogenesis, we have studied a
      series of 98 children with acute lymphoblastic leukemia and 14 leukemic cell
      lines using several indicators of MMR defects. Microsatellite markers were
      compared between blast and normal DNA from the same patients and mutations were
      sought in mononucleotide repeat sequences of BAX and TGF-beta receptor II (TGF
      beta RII). The absence of microsatellite instability (MI) and the absence of
      mutations in the genes examined from patient's leukemic cells contrasted with the
      observation that half of the cell lines displayed a high degree of MI and that
      three of seven of these mutator cell lines harbored mutations in BAX and/or TGF
      beta RII. From these results we conclude that MMR defects are very uncommon in
      freshly isolated blasts but are likely to be selected for during the
      establishment of cell lines.

PMID- 9639520
TI  - Differential effects of chondroitin sulfates A and B on monocyte and B-cell
      activation: evidence for B-cell activation via a CD44-dependent pathway.
AB  - At inflammatory sites, proteoglycans are both secreted by activated mononuclear
      leukocytes and released as a consequence of extracellular matrix degradation.
      Chondroitin 4-sulfate proteoglycans constitute the predominant ones produced by
      activated human monocytes/macrophages. In this study, we show that two
      chondroitin 4-sulfate forms, CSA and CSB, can activate distinct peripheral blood
      mononuclear cell types. Whereas CSA activates monocytes (to secrete monokines),
      CSB activates B-cells (to proliferate). In contrast, the chondroitin 6-sulfate
      CSC and heparin do not exert these functional effects. We further show that CD44
      monoclonal antibodies block CSB-induced B-cell proliferation. These findings
      point to glycosaminoglycans, and specifically chondroitin 4-sulfates, as a novel
      class of immunological mediators at inflammatory sites. Furthermore, the data
      link CD44 to B-cell activation, paralleling the established roles of CD44 in T
      cell and monocyte activation.

PMID- 9639522
TI  - Chromosomal and gene amplification in diffuse large B-cell lymphoma.
AB  - Chromosomal translocations leading to deregulation of specific oncogenes
      characterize approximately 50% of cases of diffuse large B-cell lymphomas (DLBL).
      To characterize additional genetic features that may be of value in delineating
      the clinical characteristics of DLBL, we studied a panel of 96 cases at diagnosis
      consecutively ascertained at the Memorial Sloan-Kettering Cancer Center (MSKCC)
      for incidence of gene amplification, a genetic abnormality previously shown to be
      associated with tumor progression and clinical outcome. A subset of 20 cases was
      subjected to comparative genomic hybridization (CGH) analysis, which identified
      nine sites of chromosomal amplification (1q21-23, 2p12-16, 8q24, 9q34, 12q12-14,
      13q32, 16p12, 18q21-22, and 22q12). Candidate amplified genes mapped to these
      sites were selected for further analysis based on their known roles in lymphoid
      cell and lymphoma development, and/or history of amplification in tumors. Probes
      for six genes, which fulfilled these criteria, REL (2p12-16), MYC (8q24), BCL2
      (18q21), GLI, CDK4, and MDM2 (12q13-14), were used in a quantitative Southern
      blotting analysis of the 96 DLBL DNAs. Each of these genes was amplified (four or
      more copies) with incidence ranging from 11% to 23%. This analysis is consistent
      with our previous finding that REL amplification is associated with extranodal
      presentation. In addition, BCL2 rearrangement and/or REL, MYC, BCL2, GLI, CDK4,
      and MDM2 amplification was associated with advanced stage disease. These data
      show, for the first time, that amplification of chromosomal regions and genes is
      a frequent phenomenon in DLBL and demonstrates their potential significance in
      lymphomagenesis.

PMID- 9639523
TI  - Interleukin-6-induced inhibition of multiple myeloma cell apoptosis: support for
      the hypothesis that protection is mediated via inhibition of the JNK/SAPK
      pathway.
AB  - The mechanism by which interleukin-6 (IL-6) protects multiple myeloma (MM) plasma
      cells from apoptosis induced by anti-fas antibodies and dexamethasone was
      studied. Anti-apoptotic concentrations of IL-6 had no effect on cell-cycle
      distribution or activation of RAF-1 or ERK in dexamethasone- or anti-fas-treated
      8226 and UCLA #1 MM cell lines. However, IL-6-dependent protection of viability
      correlated with an inhibition of dexamethasone- and anti-fas-induced activation
      of jun kinase (JNK) and AP-1 transactivation. To test the hypothesis that
      cytokine-induced protection was mediated through inhibition of JNK/c-jun, we also
      inhibited c-jun function in 8226 cells via introduction of a mutant dominant
      negative c-jun construct. Mutant c-jun-containing MM cells were also resistant to
      anti-fas-induced apoptosis but were significantly more sensitive to dexamethasone
      induced apoptosis. These results support the notion that IL-6 protects MM cells
      against anti-fas through its inhibitory effects on JNK/c-jun but indicate
      protection against dexamethasone occurs through separate, yet unknown pathways.

PMID- 9639524
TI  - Interleukin-15 is an autocrine/paracrine viability factor for cutaneous T-cell
      lymphoma cells.
AB  - In this study we investigated the role of interleukin-15 (IL-15) in the
      immunobiology of cutaneous T-cell lymphoma (CTCL) cells. Using cell culture
      techniques, reverse transcriptase-polymerase chain reaction (RT-PCR), and
      immunhistochemistry we found that IL-15, like IL-7, is a growth factor for the
      Sezary cell line SeAx and that both cytokines prolonged the survival of malignant
      T cells directly isolated from Sezary syndrome (SS) patients. Both IL-15 and IL-7
      were more potent than IL-2. IL-4 and IL-9, whose receptors share the same gamma
      chain with the receptors of IL-2, IL-7, and IL-15, did not sustain the growth of
      CTCL cells, indicating that signaling through the common gamma chain (gammac) is
      not sufficient for continuous growth. IL-13 and tumor necrosis factor-alpha (TNF
      alpha) had no effect. IL-7 and IL-15 also supported the growth of SeAx cells in
      the presence of the apoptosis inducing agents dexamethasone and retinoic acid.
      The analysis of patient Sezary cells and three CTCL cell lines by RT-PCR showed
      that all these cells expressed IL-15 mRNA, but only a few (25%) produced IL-7
      mRNA. Immunohistological analyses of skin biopsy samples of SS and Mycosis
      fungoides patients showed immunoreactivity for IL-15 in basal cell layer
      keratinocytes and in the infiltrating lymphocytes. We conclude that IL-15 is a
      growth or viability factor for CTCL-derived cell lines or shortly cultivated
      Sezary cells. The findings that IL-15 mRNA can be detected in Sezary syndrome
      peripheral blood mononuclear cells and that the IL-15 protein is detected in skin
      sections from CTCL patients suggest that IL-15 plays an important role in the
      biology of CTCL.

PMID- 9639525
TI  - Prednisolone resistance in childhood acute lymphoblastic leukemia: vitro-vivo
      correlations and cross-resistance to other drugs.
AB  - As an important determinant of response to chemotherapy, accurate measurement of
      cellular drug resistance may provide clinically relevant information. Our
      objectives in this study were to determine the relationship between in vitro
      resistance to prednisolone (PRD) measured with the colorimetric methyl-thiazol
      tetrazolium (MTT) assay, and (1) short-term clinical response to systemic PRD
      monotherapy, (2) long-term clinical outcome after combination chemotherapy within
      all patients and within the subgroups of clinical good and poor responders to
      PRD, and (3) in vitro resistance to 12 other drugs in 166 children with newly
      diagnosed acute lymphoblastic leukemia (ALL). The 12 clinical poor PRD responders
      had ALL cells that were median 88-fold more in vitro resistant to PRD than 131
      good responders (P = .013). Within all patients, increased in vitro resistance to
      PRD predicted a significantly worse long-term clinical outcome, at analyses with
      and without stratification for clinical PRD response, and at multivariate
      analysis (P </= .001). Within both the clinical good and poor responder
      subgroups, increased in vitro resistance to PRD was associated with a worse
      outcome, which was significant within the group of clinical good responders (P <
      .001). LC50 values, ie, lethal concentrations to 50% of ALL cells, for PRD and
      each other drug correlated significantly with those of all other 12 drugs, with
      an average correlation coefficient of 0.44 (standard deviation 0.05). The highest
      correlations were found between structurally related drugs. In conclusion, in
      vitro resistance to PRD was significantly related to the short-term and long-term
      clinical response to chemotherapy, the latter also within the subgroup of
      clinical good responders to PRD. There was a more general in vitro cross
      resistance between anticancer drugs in childhood ALL, although drug-specific
      activities were recognized.

PMID- 9639526
TI  - Mutations of the NF1 gene in children with juvenile myelomonocytic leukemia
      without clinical evidence of neurofibromatosis, type 1.
AB  - Juvenile myelomonocytic leukemia (JMML) is a pediatric myelodysplastic syndrome
      that is associated with neurofibromatosis, type 1 (NF1). The NF1 tumor suppressor
      gene encodes neurofibromin, which regulates the growth of immature myeloid cells
      by accelerating guanosine triphosphate hydrolysis on Ras proteins. The purpose of
      this study was to determine if the NF1 gene was involved in the pathogenesis of
      JMML in children without a clinical diagnosis of NF1. An in vitro transcription
      and translation system was used to screen JMML marrows from 20 children for NF1
      mutations that resulted in a truncated protein. Single-stranded conformational
      polymorphism analysis was used to detect RAS point mutations in these samples. We
      confirmed mutations of NF1 in three leukemias, one of which also showed loss of
      the normal NF1 allele. An NF1 mutation was detected in normal tissue from the
      only patient tested and this suggests that JMML may be the presenting feature of
      NF1 in some children. Activating RAS mutations were found in four patients; as
      expected, none of these samples harbored NF1 mutations. Because 10% to 14% of
      children with JMML have a clinical diagnosis of NF1, these data are consistent
      with the existence of NF1 mutations in approximately 30% of JMML cases.

PMID- 9639527
TI  - The evolution of B precursor leukemia in the Emu-ret mouse.
AB  - Emu-ret mice carrying an RFP/RET fusion gene under the transcriptional control of
      the immunoglobulin heavy chain enhancer develop B lineage leukemias/lymphomas. We
      have characterized B-cell development in these mice before the onset of clinical
      disease to determine the steps involved in leukemogenesis. Flow cytometry reveals
      that the CD45R+CD43(+)CD24(+)BP-1(+) late pro-B-cell population is markedly
      expanded in the bone marrow of 3- to 5-week-old Emu-ret mice. Compared with late
      pro-B cells from transgene-negative mice, Emu-ret late pro-B cells have a limited
      capacity to differentiate in interleukin (IL)-7 and a higher incidence of VDJ
      rearrangements, but a similar cell cycle profile. In contrast,
      CD45R+CD43(+)CD24(+)BP-1(-) early pro-B cells from 3- to 5-week-old Emu-ret mice,
      which also express the RFP/RET transgene, differentiate in IL-7 similarly to
      their normal counterparts. Furthermore, early pro-B cells from Emu-ret and
      transgene-negative mice have an identical pattern of growth inhibition when
      exposed to interferons (IFNs)-alpha/beta and -gamma, whereas, pro-B-cell leukemia
      lines derived from Emu-ret mice are markedly less sensitive to growth inhibition
      by these IFNs. In 13-week-old well-appearing Emu-ret mice, late pro-B cells
      upregulate CYCLIN D1 expression and downregulate CASPASE-1 expression in a
      pattern that correlates with the emergence of B precursor cells in the peripheral
      blood and the loss of other B lineage subsets in the bone marrow. Taken together,
      these results suggest that the expression of the RFP/RET transgene initially
      prevents the normal elimination of late pro-B cells with nonproductive
      rearrangements. Secondary events that simultaneously disturb the normal
      transcriptional regulation of genes involved in the control of the cell cycle and
      apoptosis may allow for subsequent malignant transformation within the expanded
      late pro-B-cell population.

PMID- 9639528
TI  - Complement fragment-induced release of neutrophils from bone marrow and
      sequestration within pulmonary capillaries in rabbits.
AB  - Infusion of complement fragments induces rapid sequestration of neutrophils
      within the pulmonary capillaries. This study examined the contributions of the
      bone marrow (BM) and the liver to the accumulation of neutrophils within the
      lungs. Complement fragments induced the release of neutrophils from the BM within
      7 minutes of infusion, and these neutrophils sequestered in the lungs immediately
      upon reaching the pulmonary capillaries. Neutrophils expressing high levels of L
      selectin were preferentially retained within the pulmonary microvasculature. By
      30 minutes after the infusion was stopped, the circulating neutrophil counts had
      increased, primarily because of release from the BM. The number of neutrophils
      sequestered in the lung had decreased by only 27%, and the number of neutrophils
      in the liver increased by 223%. These studies indicate that complement fragments
      induce the release of neutrophils from the BM far more rapidly than previously
      described. These newly released neutrophils immediately sequester within the
      lung, increasing the number of neutrophils available to injure the lung many fold
      beyond the number that were circulating before infusion. The preferential
      retention of L-selectin-expressing neutrophils likely reflects the requirement
      for L-selectin-mediated adhesion in maintaining sequestered neutrophils within
      the pulmonary microvasculature. The number of circulating neutrophils reflects a
      balance between pulmonary sequestration, rapid release from the BM, and uptake by
      the liver and other organs.

PMID- 9639529
TI  - Epstein-Barr virus infects and induces apoptosis in human neutrophils.
AB  - The role of neutrophils during Epstein-Barr virus (EBV) infection is not known.
      Disruption of the initial and nonspecific immune response may favor the spread of
      EBV infection. We have previously shown that EBV interacts with human neutrophils
      and modulates protein expression. In this study we have investigated the ability
      of EBV to infect neutrophils. Electron microscopy studies showed penetration of
      virus and its subsequent localization to the nucleus. The presence of viral
      genomes in isolated nuclei from neutrophils was also shown by polymerase chain
      reaction (PCR). Expression of viral transcripts like EBNA-2 (Epstein-Barr nuclear
      antigen-2) and ZEBRA (BamHI Z EBV replication activator) was not detected by
      reverse transcriptase (RT)-PCR, suggesting that EBV does not seem to establish a
      latent or a lytic infection in neutrophils. However, at 20 hours post-EBV
      infection, 77% of cells were apoptotic as compared to 22% in uninfected cell
      cultures, as evaluated by flow cytometry. This EBV-induced apoptosis was
      prevented by the addition of granulocyte-macrophage colony-stimulating factor to
      the cell cultures. Apoptotic cell death seems to implicate the Fas/Fas ligand (L)
      pathway, as reflected by an increase of Fas/Fas L expression on neutrophils
      treated with EBV and an increase of soluble Fas L, which may function in an
      autocrine/paracrine pathway to mediate cell death. Lastly, EBV genome was
      detected from neutrophils of infectious mononucleosis (IM) patients in contrast
      to neutrophils obtained from healthy EBV-seropositive donors. Our findings on the
      interactions of EBV with neutrophils will then provide new insights on the
      immunosuppressive effects associated with EBV infection.

PMID- 9639530
TI  - Intracellular storage and regulated plasma membrane expression of human
      complement receptor type 1 in rat basophil leukemia cell transfectants.
AB  - Polymorphonuclear neutrophils (PMN) contain multiple distinct secretory
      compartments that are sequentially mobilized during cell activation. Complement
      receptor type 1 (CR1) is a marker for a readily mobilizable secretory vesicle
      compartment, which can undergo exocytic fusion with the plasma membrane
      independently of secretion of traditional granule contents. The basis for the
      formation of these distinct compartments is incompletely understood. Primary and
      secondary granules are generated directly from the Golgi complex during different
      stages of development of the cell, obviating the need for sorting signals for
      proper packaging of their constituents. To determine whether the secretory
      vesicles are formed in a similar manner, we studied a stable rat basophilic
      leukemia cell line (RBL-CR1) transfected with a plasmid containing the cDNA of
      human CR1 driven by a viral promoter. The CR1 was present primarily
      intracellularly in small vesicles resembling the CR1 storage pools in resting
      PMN. Activation of RBL-CR1 resulted in translocation of intracellular CR1 to the
      plasma membrane, with mobilization requirements different from those of the
      classical RBL granules. Thus, in RBL-CR1, continuously synthesized CR1 is stored
      and upregulated in much the same way as in PMN. This suggests that differential
      timing of gene expression is not essential for proper storage of CR1 and that
      other sorting mechanisms are involved, which can be studied in RBL-transfectants.

PMID- 9639531
TI  - An erythroid-specific transcript generates the soluble form of NADH-cytochrome b5
      reductase in humans.
AB  - Two forms of NADH-cytochrome b5 reductase (b5R), an erythrocyte-restricted
      soluble form, active in methemoglobin reduction, and a ubiquitous membrane
      associated form involved in lipid metabolism, are produced from one gene. In the
      rat, the two forms are generated from alternative transcripts differing in the
      first exon, however, biogenesis of human b5R was less understood. Recently, two
      different transcripts (M and S), differing in the first exon were also described
      in humans. Here, we have investigated the tissue-specificity and the role of the
      S-transcript in the generation of soluble b5R. By RNase protection assays
      designed to simultaneously detect alternative b5R transcripts in the same sample,
      the S transcript was undetectable in nonerythroid and in erythroleukemic K562
      cells induced to differentiate, but was present in terminal erythroblast
      cultures, and represented a major b5R transcript in reticulocytes. Analysis of
      the translation products of the M- and S-transcripts in HeLa cells transfected
      with the corresponding cDNAs demonstrated that the S-transcript generates soluble
      b5R, presumably from an internal initiation codon. Our results indicate that the
      S-transcript is expressed at late stages of erythroid maturation to generate
      soluble b5R.

PMID- 9639532
TI  - Analysis of the human ferrochelatase promoter in transgenic mice.
AB  - Ferrochelatase catalyzes the chelation of ferrous iron and protoporphyrin to form
      heme. It is expressed as a housekeeping gene in all cells, but is upregulated
      during erythropoiesis. Ferrochelatase activity is deficient in the inherited
      disease protoporphyria as a result of heterogeneous mutations. Although human
      ferrochelatase is transcribed from a single promoter in both nonerythroid and
      erythroid cells, previous studies using transient transfection assays failed to
      demonstrate erythroid-specific increased expression from 4.0 kb of the human
      ferrochelatase promoter containing the erythroid cis-elements, GATA and NF-E2.
      The present study analyzes the in vivo regulation of the ferrochelatase gene to
      provide insights into the mechanism of its erythroid-specific enhancement.
      Transgenic (TG) mouse lines were generated in which the luciferase reporter gene
      was driven by either a 150-bp ferrochelatase minimal promoter (-0.15 TG) or by a
      4.0 kb extended 5' upstream region (-4.0 TG). Expression of the -4.0 TG transgene
      was generally consistent with the endogenous gene during embryonic development
      and in nonerythroid and erythroid tissues as demonstrated by Northern blotting
      and mRNA in situ hybridization. The -4.0 TG was expressed at a higher level than
      the -0.15 TG in nonerythroid and erythroid tissues, including during
      extramedullary erythropoiesis induced by n-acetylphenylhydrazine injection. The
      enhanced erythroid expression of the -4.0 TG correlates with the appearance of a
      DNase I hypersensitive site in the 5' flanking region of the transgene.
      Therefore, in the context of chromosomal integration, the 5' flanking region of
      the ferrochelatase gene is necessary and sufficient to confer high levels of
      transgene expression in erythroid tissue.

PMID- 9639533
TI  - Temporal synthesis of band 3 oligomers during terminal maturation of mouse
      erythroblasts. Dimers and tetramers exist in the membrane as preformed stable
      species.
AB  - Band 3, the anion transport protein of the erythrocyte membrane, exists in the
      membrane as a mixture of dimers (B3D) and tetramers (B3T). The dimers are not
      linked to the skeleton and constitute the free mobile band 3 fraction. The
      tetramers are linked to the skeleton by their interaction with ankyrin. In this
      report we have examined the temporal synthesis and assembly of band 3 oligomers
      into the plasma membrane during red cell maturation. The oligomeric state of
      newly synthesized band 3 in early and late erythroblasts was analyzed by size
      exclusion high-pressure liquid chromatography of band 3 extracts derived by mild
      extraction of plasma membranes with the nonionic detergent C12E8 (octaethylene
      glycol n-dodecyl monoether). This analysis revealed that at the early
      erythroblast stage, the newly synthesized band 3 is present predominantly as
      tetramers, whereas at the late stages of erythroid maturation, it is present
      exclusively as dimers. To examine whether the dimers and tetramers exist in the
      membrane as preformed stable species or whether they are interconvertible, the
      fate of band 3 species synthesized during erythroblast maturation was examined by
      pulse-chase analysis. We showed that the newly synthesized band 3 dimers and
      tetramers are stable and that there is no interconversion between these species
      in erythroblast membranes. Pulse-chase analysis followed by cellular
      fractionation showed that, in early erythroblasts, the newly synthesized band 3
      tetramers are initially present in the microsomal fraction and later incorporated
      stably into the plasma membrane fraction. In contrast, in late erythroblasts the
      newly synthesized band 3 dimers move rapidly to the plasma membrane fraction but
      then recycle between the plasma membrane and microsomal fractions. Fluorescence
      photobleaching recovery studies showed that significant fractions of B3T and B3D
      are laterally mobile in early and late erythroblast plasma membranes,
      respectively, suggesting that many B3T-ankyrin complexes are unattached to the
      membrane skeleton in early erythroblasts and that the membrane skeleton has yet
      to become tightly organized in late erythroblasts. We postulate that in early
      erythroblasts, band 3 tetramers are transported through microsomes and stably
      incorporated into the plasma membrane. However, when ankyrin synthesis is
      downregulated in late erythroblasts, it appears that B3D are rapidly transported
      to the plasma membrane but then recycled between the plasma membrane and
      microsomal compartments. These observations may suggest novel roles for membrane
      skeletal proteins in stabilizing integral membrane protein oligomers at the
      plasma membrane and in regulating the endocytosis of such proteins.

PMID- 9639534
TI  - To GpIb or not to GpIb.

PMID- 9639535
TI  - Serglycin expression during monocytic differentiation of U937-1 cells.
AB  - Serglycin is the major proteoglycan in most hematopoietic cells, including
      monocytes and macrophages. The monoblastic cell line U937-1 was used to study the
      expression of serglycin during proliferation and differentiation. In unstimulated
      proliferating U937-1 cells serglycin mRNA is nonconstitutively expressed. The
      level of serglycin mRNA was found to correlate with the synthesis of chondroitin
      sulfate proteoglycan (CSPG). The U937-1 cells were induced to differentiate into
      different types of macrophage-like cells by exposing the cells to PMA, RA, or
      VitD3. These inducers of differentiation affected the expression of serglycin
      mRNA in three different ways. The initial upregulation seen in the normally
      proliferating cells was not observed in PMA treated cells. In contrast, RA
      increased the initial upregulation, giving a reproducible six times increase in
      serglycin mRNA level from 4 to 24 h of incubation, compared to a four times
      increase in the control cells. VitD3 had no effect on the expression of serglycin
      mRNA. The incorporation of (35S)sulfate into CSPG decreased approximately 50% in
      all three differentiated cell types. Further, the (35S)CSPGs expressed were of
      larger size in PMA treated cells than controls, but smaller after RA treatment.
      This was due to the expression of CSPGs, with CS-chains of 25 and 5 kDa in PMA
      and RA treated cells, respectively, compared to 11 kDa in the controls. VitD3 had
      no significant effect on the size of CSPG produced. PMA treated cells secreted
      75% of the (35S)PGs expressed, but the major portion was retained in cells
      treated with VitD3 or RA. The differences seen in serglycin mRNA levels, the
      macromolecular properties of serglycin and in the PG secretion patterns, suggest
      that serglycin may have different functions in different types of macrophages.

PMID- 9639536
TI  - Site localization of sialyl Lewis(x) antigen on alpha1-acid glycoprotein by high
      performance liquid chromatography-electrospray mass spectrometry.
AB  - A simple, fast and sensitive method was developed to verify the presence of the
      sialyl Lewis(x) antigen on an N-linked glycoprotein. High performance liquid
      chromatography-electrospray mass spectrometry (HPLC-ESI/MS) was used to identify
      which of the five N-linked glycosylation sites of human plasma alpha1-acid
      glycoprotein (orosomucoid, OMD) contain the sialyl Lewis(x) antigen. OMD was
      digested with proteolytic enzymes and analyzed by reversed phase chromatography
      coupled with on-line ESI/MS. A tandem mass spectrometry experiment was designed
      to detect the presence of the sialyl Lewis(x) antigen based on the observation of
      an 803 mass to charge ratio ( m/z ) ion produced in the intermediate pressure
      region of the ESI interface. The ESI/MS signal at m/z 803 is consistent with an
      oxonium ion for a glycan structure containing NeuAc, Gal, GlcNAc, and Fuc. The
      identity of the m/z 803 ion was confirmed by ESI/MS/MS analysis of the m/z 803
      fragment ion and comparison with a sialyl Lewis(x) standard. The stereochemistry
      and linkage positions were assigned using previous NMR analysis but could be
      determined with permethylation analysis if necessary. The analysis of OMD gave a
      pattern showing signal for the sialyl Lewis(x) antigen coeluting with each of the
      five N-linked glycopeptides. The ability to monitor sialyl Lewis(x) expression at
      each of the five sites is of interest in the study of OMD's role in inflammatory
      diseases.

PMID- 9639537
TI  - GPI anchor biosynthesis in yeast: phosphoethanolamine is attached to the alpha1,4
      linked mannose of the complete precursor glycophospholipid.
AB  - Cells synthesize the GPI anchor carbohydrate core by successively adding N
      acetylglucosamine, three mannoses, and phosphoethanolamine (EtN-P) onto
      phosphatidylinositol, thus forming the complete GPI precursor lipid which is then
      added to proteins. Previously, we isolated a GPI deficient yeast mutant
      accumulating a GPI intermediate containing only two mannoses, suggesting that it
      has difficulty in adding the third, alpha1,2-linked Man of GPI anchors. The
      mutant thus displays a similar phenotype as the mammalian mutant cell line S1A-b
      having a mutation in the PIG-B gene. The yeast mutant, herein named gpi10-1 ,
      contains a mutation in YGL142C, a yeast homolog of the human PIG-B. YGL142C
      predicts a highly hydrophobic integral membrane protein which by sequence is
      related to ALG9, a yeast gene required for adding Man in alpha1,2 linkage to N
      glycans. Whereas gpi10-1 cells grow at a normal rate and make normal amounts of
      GPI proteins, the microsomes of gpi10-1 are completely unable to add the third
      Man in an in vitro assay. Further analysis of the GPI intermediate accumulating
      in gpi10 shows it to have the structure Manalpha1-6(EtN-P-)Manalpha1-4GlcNalpha1
      6(acyl) Inositol-P-lipid. The presence of EtN-P on the alpha1,4-linked Man of GPI
      anchors is typical of mammalian and a few other organisms but had not been
      observed in yeast GPI proteins. This additional EtN-P is not only found in the
      abnormal GPI intermediate of gpi10-1 but is equally present on the complete GPI
      precursor lipid of wild type cells. Thus, GPI biosynthesis in yeast and mammals
      proceeds similarly and differs from the pathway described for Trypanosoma brucei
      in several aspects.

PMID- 9639538
TI  - Cloning and expression of an alpha-2,8-polysialyltransferase (STX) from Xenopus
      laevis.
AB  - Polysialic acid (polySia) is a carbohydrate structure found on neural cell
      adhesion molecules (N-CAM). Two polysialyltransferases (polySiaTs) that catalyze
      synthesis of polySia have been described, and designated PST-1/PST/ST8SiaIV and
      STX/ST8SiaII. We cloned a polySiaT (xSTX) from a nonmammalian vertebrate, Xenopus
      laevis . xSTX had 80% amino acid similarity to the rat STX. This clone induced
      polySia expression when transfected into polySia-negative COS-1 cells. Northern
      blot analysis of whole embryos at different stages of development revealed that
      xSTX mRNA was most abundantly expressed in premetamorphic stages. The relative
      level of xSTX and N-CAM mRNAs was also examined and found to change in parallel
      to the extent of polysialylation on N-CAM. In adult tissues, the expression of
      xSTX mRNA was restricted to brain, eye and heart, which also expressed polySia.
      These results suggest that xSTX is the major enzyme responsible for the synthesis
      of polysialylated N-CAM in embryos at certain stages of development and also in
      adult tissues.

PMID- 9639539
TI  - Structural characterization and independent folding of a chimeric glycoprotein
      comprising granulocyte-macrophage colony stimulating factor and erythropoietin
      sequences.
AB  - MEN 11300 is a hybrid glycoprotein of 297 amino acids obtained by fusion of the
      cDNA encoding GM-CSF with the cDNA encoding EPO followed by transfection of the
      hybrid gene into CHO cells. The oligonucleotide construct incorporated a spacing
      sequence between the two individual cDNAs which encodes eight amino acids
      constituting a linker peptide intended to separate the GM-CSF and EPO moieties.
      The recombinant MEN 11300 protein was submitted to a detailed structural
      characterization including the verification of the entire amino acid sequence,
      the assignment of the disulfide bridges pattern, the identification of the
      glycosylation sites and the definition of the glycosidic moiety, including site
      specificity. Partial processing of the C-terminal Arg residue and the occurrence
      of N-glycosylation sites at Asn27, Asn155, Asn169, Asn214 were established.
      Moreover, O-glycosylation at Ser257 and at the N-terminal region was also
      detected. A large heterogeneity was observed in the N-glycans due to the presence
      of differently sialylated and fucosylated branched complex type oligosaccharides
      whereas O-linked glycans were constituted by GalGalNAc chains with a different
      number of sialic acids. The disulfide bridges pattern was established by direct
      FABMS analysis of the proteolytic digests or by ESMS analysis of HPLC purified
      fractions. Pairing of the eight cysteine residues resulted in Cys54-Cys96, Cys88
      Cys121, Cys138-Cys292, and Cys160-Cys164. This S-S bridges pattern is identical
      to that occurring in the individual natural GM-CSF and EPO, thus showing that the
      two protein moieties in MEN 11300 can independently acquire their native three
      dimensional structure.

PMID- 9639540
TI  - Coordinated binding of sugar, calcium, and antibody to macrophage C-type lectin.
AB  - Mouse macrophage galactose/N-acetylgalactosamine-specific C-type lectin (MMGL) is
      a type II transmembrane glycoprotein belonging to the C-type lectin family. Our
      development of monoclonal antibodies led us to discover that a calcium-dependent
      conformational change is detected by an antibody (termed mAb LOM-11) and that the
      antibody's binding to the respective site locks the lectin in an active
      conformation. These findings correspond to the divalent cation-mediated
      regulatory mechanisms in a family of cell adhesion molecule integrins that have
      gained much attention. We now provide direct evidence that mAb LOM-11 increases
      the affinity of the lectin for calcium ions as a mechanism for the conformational
      lock using a soluble recombinant form of MMGL (rML) produced in bacteria.
      Furthermore, we discovered by using an enzyme-linked immunosorbent assay that
      specific monosaccharides induced a binding site for mAb LOM-11 on the immobilized
      rML under low calcium environments. We also demonstrated that cell surface MMGL
      on a transfectant cell line underwent a conformational change upon addition of
      calcium or ligands, as detected by the binding of mAb LOM-11. These properties
      are reminiscent of ligand-induced binding sites defined for integrins. The
      present results suggest a possibility that the mAb LOM-11 binding site on the
      lectin may be a site at which protein-protein interaction helps to fine tune the
      specificity of the C-type lectins by means of coordinated recognition mechanisms.

PMID- 9639541
TI  - Fucosebeta-1-P-Ser is a new type of glycosylation: using antibodies to identify a
      novel structure in Dictyostelium discoideum and study multiple types of
      fucosylation during growth and development.
AB  - Three antibodies that recognize distinct fucose epitopes were used to study
      fucosylation during growth and development of Dictyostelium discoideum. mAb83.5
      is known to recognize an undefined "fucose epitope" on several proteins with
      serine-rich domains, while mAb CAB4, and a component of anti-horse-radish
      peroxidase, specifically recognize Fucalpha1,6GlcNAc and Fucalpha1,3GlcNAc
      residues respectively in the core of N-linked oligosaccharides. We show that mAb
      83.5 defines a new type of O-glycosylation. Serine-containing peptides incubated
      with GDPbeta[3H]Fuc and microsomes formed two fucosylated products. A neutral
      product accounting for 30% of the label did not react with the antibody, while
      the rest of the label was incorporated into a charged product which contained all
      the mAb83.5 reactive material. beta-Elimination of the labeled peptide or
      endogenous products produced [3H]Fuc-1-P, indicating phosphodiester linkage to
      serine. Fucbeta-1-P and GDP-betaFuc at 100 microM blocked mAb83.5 binding to
      endogenous and peptide products, but their alpha-linked anomers did not.
      Electrospray ionization mass spectra of the neutral and anionic labeled products
      showed major peaks of mass units corresponding to O-Fuc-Ser peptide and O-Fuc
      phospho-Ser peptide, respectively. The activity of Fuc-phosphotransferase exactly
      paralleled the accumulation of reactive glycans during growth and development.
      The expressions of N-glycan core Fucalpha1,6GlcNAc and Fucalpha1,3GlcNAc and
      their respective fucosyl transferase activities were also synchronous, but their
      developmental regulation differed from one another. Fucalpha1, 6GlcNAc was
      expressed maximally during growth but declined during development. In contrast
      core Fucalpha1,3GlcNAc epitopes were expressed almost exclusively during
      development. These findings provide direct evidence for a novel type of O
      phosphofucosylation, demonstrate the existence of an O-fucosyl transferase, and
      identify two different types of core fucosylation in the N-glycans of
      Dictyostelium.

PMID- 9639542
TI  - alpha-N-acetylgalactosamine-capping of chondroitin sulfate core region
      oligosaccharides primed on xylosides.
AB  - We previously reported that cultured mammalian cells incubated with 4
      methylumbelliferyl (MU) or p -nitrophenyl (pNP) beta-xyloside synthesize an alpha
      GalNAc-terminated pentasaccharide resembling the glycosaminoglycan-core protein
      linkage region. Here we show that human melanoma M21 cells and human
      neuroblastoma cells incubated with Xylbeta-MU/pNP also make an alpha-GalNAc
      terminated heptasaccharide containing one chondroitin disaccharide repeat. High
      performance liquid chromatography and matrix-assisted laser desorption ionization
      mass spectrometry analysis of intact or glycosidase-digested xyloside showed the
      structure as: GalNAcalphaGlcAbeta1,3GalNAcbeta1,4GlcAbeta1,3Galbe ta1,3Galbeta1,
      4Xylbeta-MU/pNP. The alpha-GalNAc-terminated xylosides can account for
      approximately 10% of the total Xylbeta-MU/pNP products ( approximately 1.5
      nmol/h/mg). These results show that GalNAcalphaGlcAbeta-modification is
      relatively abundant, but not unique to the GAG-linkage tetrasaccharide. alpha
      GalNAc addition to the GlcA residue does not appear to be an extension of general
      phase II detoxification of xenobiotics that involve glucuronidation, since M21
      cells incubated with MU synthesize only 0.3 pmol GlcAbeta-MU/h/mg protein, and
      undetectable amount of GalNAcalphaGlcAbeta-MU (<40 fmol/h/mg). Further,
      subcellular fractionation shows that the alpha- N-
      acetylgalactosaminyltransferase activity colocalizes in the Golgi with other
      glycosyl transferases and not in the ER, where xenobiotic detoxification
      glucuronosyltransferases are found. Although GalNAcalphaGlcAbeta-terminal
      modification has not been detected on naturally occurring GAG chains, the
      substantial amount of alpha-GalNAc transferase activity suggests that the alpha
      GalNAc transferase could utilize other GlcA-containing glycoconjugates as
      acceptors.

PMID- 9639543
TI  - A 340 kDa hyaluronic acid secreted by human vascular smooth muscle cells
      regulates their proliferation and migration.
AB  - The formation of atherosclerotic lesions is characterized by invasion of vascular
      smooth muscle cells (VSMC) into the tunica intima of the arterial wall and
      subsequently by increased proliferation of VSMC, a process apparently restricted
      to the intimal layer of blood vessels. Both events are preceded by the
      pathological overexpression of several growth factors, such as platelet-derived
      growth factor (PDGF) which is a potent mitogen for VSMC and can induce their
      chemotaxis. PDGF is generally not expressed in the normal artery but it is
      upregulated in atherosclerotic lesions. We have previously shown that PDGF-BB
      specifically stimulates proliferating VSMC to secrete a 340 kDa hyaluronic acid
      (HA-340). Here, we present evidence regarding the biological functions of this
      glycan. We observed that HA-340 inhibited the PDGF-induced proliferation of human
      VSMC in a dose-dependent manner and enhanced the PDGF-dependent invasion of VSMC
      through a basement membrane barrier. These effects were abolished following
      treatment of HA-340 with hyaluronidase. The effect of HA-340 on the PDGF
      dependent invasion of VSMC coincided with increased secretion of the 72-kDa type
      IV collagenase by VSMC and was completely blocked by GM6001, a hydroxamic acid
      inhibitor of matrix metalloproteinases. HA-340 did not exert any chemotactic
      potency, nor did it affect chemotaxis of VSMC along a PDGF gradient. In human
      atheromatic aortas, we found that HA-340 is expressed with a negative
      concentration gradient from the tunica media to the tunica intima and the
      atheromatic plaque. Our findings suggest that HA-340 may be linked to the
      pathogenesis of atherosclerosis, by modulating VSMC proliferation and invasion.

PMID- 9639544
TI  - Two soluble glycosyltransferases glycosylate less efficiently in vivo than their
      membrane bound counterparts.
AB  - Many Golgi glycosyltransferases are type II membrane proteins which are cleaved
      to produce soluble forms that are released from cells. Cho and Cummings recently
      reported that a soluble form of alpha1, 3-galactosyltransferase was comparable to
      its membrane bound counterpart in its ability to galactosylate newly synthesized
      glycoproteins (Cho,S.K. and Cummings,R.D. (1997) J. Biol. Chem., 272, 13622
      13628). To test the generality of their findings, we compared the activities of
      the full length and soluble forms of two such glycosyltransferases, ss1,4 N
      Acetylgalactosaminyltransferase (GM2/GD2/ GA2 synthase; GalNAcT) and beta
      galactoside alpha2,6 sialyltransferase (alpha2,6-ST; ST6Gal I), for production of
      their glycoconjugate products in vivo . Unlike the full length form of GalNAcT
      which produced ganglioside GM2 in transfected cells, soluble GalNAcT did not
      produce detectable GM2 in vivo even though it possessed in vitro GalNAcT activity
      comparable to that of full length GalNAcT. When compared with cells expressing
      full length alpha2,6-ST, cells expressing a soluble form of alpha2,6-ST contained
      3-fold higher alpha2,6-ST mRNA levels and secreted 7-fold greater alpha2,6-ST
      activity as measured in vitro , but in striking contrast contained 2- to 4-fold
      less of the alpha2,6-linked sialic acid moiety in cellular glycoproteins in vivo
      . In summary these results suggest that unlike alpha1,3-galactosyltransferase the
      soluble forms of these two glycosyltransferases are less efficient at
      glycosylation of membrane proteins and lipids in vivo than their membrane bound
      counterparts.

PMID- 9639545
TI  - Microneurographic research on sympathetic nerve responses to environmental
      stimuli in humans.
AB  - The sympathetic nervous system plays an important role to maintain the
      homeostasis of vital functions in humans against environmental stimuli.
      Sympathetic nerve responses to environmental stimuli in humans have been assessed
      conventionally using rather indirect methods by analyzing the responses of
      effector organs or by measuring the changes in plasma norepinephrine level.
      Meanwhile, the microneurography technique has enabled us to approach the
      sympathetic nervous system in humans more directly. By applying this technique,
      it has become possible to investigate how the human sympathetic nervous system
      responds to different kinds of environmental stimuli. In this paper, the
      usefulness of microneurography as a research tool in environmental physiology is
      shown together with a review of microneurographic findings on sympathetic nerve
      responses to environmental stimuli in humans.

PMID- 9639546
TI  - Force-velocity relation of sliding of skeletal muscle myosin, arranged on a
      paramyosin filament, on actin cables.
AB  - To investigate in vitro ATP-dependent sliding of regularly arranged myosin
      molecules on actin filaments, we prepared thick hybrid filaments in which myosin
      molecules isolated from rabbit skeletal muscle were arranged around the
      paramyosin core (length, 10-20 micron; diameter, </=0.2 micron) obtained from a
      molluscan smooth muscle. A single to a few thick hybrid filaments were attached
      to a polystyrene bead (diameter, 4.5 micron; specific gravity, 1.5) and made to
      slide on actin filament arrays (actin cables) in the internodal cell of an alga,
      mounted on the rotor of a centrifuge microscope. The bead was subjected to
      centrifugal forces serving as external loads to the ATP-dependent actin-myosin
      sliding. The maximum unloaded sliding velocity of the thick filament attached
      bead (mean, 3.4 micron/s; 20-23 degrees C) was significantly higher than that of
      the bead coated with randomly oriented myosin molecules reported previously. The
      steady-state force-velocity (P-V) relations obtained were qualitatively similar
      to those in intact skeletal muscle fibers. These results indicate that this in
      vitro motility assay system retains the basic characteristics of contracting
      skeletal muscle fibers, and that it may be effectively used to study mechanisms
      underlying the steady-state P-V characteristics of ATP-dependent actin-myosin
      sliding using various recombinant myosins produced in nonmuscle cells.

PMID- 9639547
TI  - Effects of Ca2+ and epinephrine on Ca2+ recirculation fraction and total Ca2+
      handling in canine left ventricles.
AB  - We investigated the effects of intracoronary Ca2+ and epinephrine on the
      intracellular Ca2+ recirculation fraction (RF) and total Ca2+ handling in the
      left ventricle (LV) of the excised cross-circulated canine heart preparation. We
      analyzed LV postextrasystolic potentiation (PESP) following a spontaneous
      extrasystole that occurred sporadically under constant atrial pacing. All PESPs
      decayed in alternans and none decayed monotonically. We extracted an exponential
      decay component from the alternans PESP, determined its beat constant (taue), and
      calculated RF = exp(-1/taue). Increased intracoronary Ca2+ slightly increased
      taue and RF, but epinephrine did not change them, although both agents enhanced
      LV contractility 2-3 times. Neither Ca2+ nor epinephrine affected the sinusoidal
      decay of the alternans PESP. These results indicate that RF via the sarcoplasmic
      reticulum was slightly augmented by Ca2+, but not by epinephrine. We combined
      these RF data with LV Ca2+ handling O2 consumption data and obtained 40-110
      micromol/kg as the total amount of Ca2+ handled in one cardiac cycle in the
      control and enhanced contractile states. These results indicate that this new LV
      level approach seems to better the understanding of the Ca2+ mass dynamics
      responsible for the mechanoenergetics enhanced by inotropic interventions.

PMID- 9639548
TI  - Basic fibroblast growth factor-mediated lymphangiogenesis of lymphatic
      endothelial cells isolated from dog thoracic ducts: effects of heparin.
AB  - We have attempted to evaluate whether, similar to the angiogenesis of blood
      vessels, cultures of lymphatic endothelial cells (LEC) isolated from dog thoracic
      ducts have an ability to induce lymphangiogenesis in response to basic fibroblast
      growth factor (bFGF), then to examine the effects of heparin on the bFGF-mediated
      morphogenesis. The effects of bFGF and/or heparin on the proliferation and
      migration of the LEC were evaluated by changing the number of the subconfluent
      cells and by wound migration assay, respectively. The effects of the agents on
      invasion and tube formation of the LEC into a three-dimensional collagen gel and
      on collagen gel induced tube formation of the LEC were also investigated by a
      phase-contrast microscope and an electron microscope. The bFGF (10 ng/ml) caused
      a significant induction of proliferation and migration of the LEC, the induction
      of which was augmented dose-dependently by an additional treatment with heparin
      ranging from 1 to 100 microg/ml. The bFGF produced invasion and tube formation of
      the LEC into a three-dimensional collagen gel. The bFGF also facilitated to form
      capillary-like tubes of the LEC between two layers of collagen gels. Heparin (10
      microg/ml) accelerated both processes of bFGF-mediated lymphangiogenesis of the
      LEC. These findings suggest that the cultured LEC isolated from dog thoracic
      ducts have an ability to form lymphatic capillary-like tubes in response to bFGF
      and that heparin accelerates dose-dependently the process of the bFGF-mediated
      neovascularization of lymph vessels.

PMID- 9639549
TI  - Nonshivering thermoregulatory responses in trained athletes: effects of physical
      fitness and body fat.
AB  - We studied the difference of thermoregulatory responses between trained male
      athletes (TR, n = 9) and untrained men (UT, n = 7) during 60 min of cold exposure
      (15 degrees C) without shivering, and examined the effects of physical fitness
      and body fat on these responses. Mean skin temperature (Tsk), esophageal
      temperature (Tes), and skin conductance (Kb) were similar between TR and UT, and
      heat production (M) for TR increased significantly during exposure at 15 degrees
      C. The M at 15 degrees C correlated positively with maximal oxygen uptake and
      negatively with body fat (%BF), but not with Tes. The Kb correlated negatively
      with Tes and positively with Tsk. The %BF also correlated negatively with Kb and
      Tsk during exposure at 15 degrees C, and the slope of %BF vs. Tsk relationship
      was significantly steeper in TR than in UT. These results suggest that (1) body
      temperature is maintained by the reduction of skin conductance, and (2) heat
      insulation independent of body fat is enhanced in trained athletes during cold
      exposure without shivering.

PMID- 9639550
TI  - Effects of different types of clothing on circadian rhythms of core temperature
      and urinary catecholamines.
AB  - This study investigated the effects of three different types of clothing on the
      circadian rhythms of core temperature and urinary catecholamines. One type of
      clothing consisted of long-sleeved shirts, full-length trousers, and socks (Type
      L, 1,042 g); the second type was of half-sleeved shirts and knee-length trousers
      (Type H, 747 g); the third type was of Type H during the daytime and Type L
      during night sleep (Type M). Six healthy females participated in this study where
      rectal temperature, skin temperatures, heart rate, and urinary catecholamines
      were continuously measured for 37.5 h at an ambient temperature of 23.8 +/- 0.2
      degrees C and a relative humidity of 60 +/- 5%. The results were as follows: (1)
      The nocturnal minimum of rectal temperature decreased significantly in the
      sequence Type L < Type M < Type H clothing, and 27.2 and 12.4% of the circadian
      amplitude were influenced by type of clothing during the daytime and the
      nighttime, respectively. (2) The rise of skin temperatures in the extremities
      increased significantly more after the subjects retired for sleep with Type M or
      Type H clothing than with Type L. (3) Urinary catecholamines decreased more in
      the evening and increased more in the morning with Type H and Type M clothing
      than with Type L. These results show that the circadian rhythm of core
      temperature, especially the nocturnal minimum value, was influenced by the type
      of clothing worn not only during the nighttime, but also during the daytime.

PMID- 9639551
TI  - Role of platelet-activating factor on extravascular lung water after coronary
      reperfusion in dogs.
AB  - Platelet-activating factor (PAF), one of the harmful substances released after
      coronary reperfusion, has been reported to increase pulmonary vascular
      permeability and induce pulmonary edema. In this study, we sought to examine the
      possible role of PAF in the genesis of pulmonary edema after coronary
      reperfusion. Extravascular lung water (EVLW) was measured by the thermal-dye
      double indicator dilution method during coronary ligation and after reperfusion
      in situ in dogs. The proximal left anterior descending coronary artery was
      occluded for 15 min and reperfused in 5 dogs (group 1), while five other dogs
      (group 2) were treated with PAF-antagonist (TCV-309, 1 mg/kg) before coronary
      artery occlusion. EVLW and hemodynamic indices were measured at baseline, 15 min
      of coronary occlusion, and 15 and 30 min after coronary reperfusion. EVLW
      increased at 15 min of coronary occlusion in both groups, but there was no
      significant difference between the two groups (6.4 to 10.3 ml/kg and 5.4 to 7.1
      ml/kg in groups 1 and 2, respectively). After coronary reperfusion, EVLW
      increased further in group 1 (6.4 to 16.5 ml/kg, p < 0.01), but no further
      increase was observed in group 2 at 30 min after coronary reperfusion. There were
      no significant differences in hemodynamic indices between the two groups
      throughout the test. Thus, PAF-antagonist attenuated the increase in EVLW after
      coronary reperfusion independent of hemodynamic indices, and hence, PAF may play
      an important role in the genesis of pulmonary edema caused by coronary
      reperfusion.

PMID- 9639552
TI  - Changes in core temperature and thermoeffector thresholds in exercise-trained
      rats.
AB  - Spontaneous running in a running wheel has emerged as an alternative method of
      exercise in small animals. The present study investigated how exercise training
      with a running wheel affects core temperature level and thermoeffector thresholds
      in rats. Female rats were allowed to run freely in the wheel for 6 months.
      Sedentary controls did not exercise during the same period. After the exercise
      training period, they were loosely restrained and their threshold core
      temperatures for tail skin vasodilation and cold-induced thermogenesis were
      determined by warming or cooling the animals by use of a chronically implanted
      intravenous thermode. Resting and threshold core temperatures of the exercise
      trained rats were higher than those of the sedentary controls. The results
      suggest that in rat, exercise training with a running wheel shifts threshold
      temperatures for heat loss and heat production to high levels, which may result
      in a rise in core temperature level.

PMID- 9639553
TI  - Plasma insulin and growth hormone during antarctic residence.
AB  - Circulatory levels of insulin and growth hormone (GH) were estimated in nine
      tropical euglycemic men in New Delhi and during the first week of every month of
      stay in Dakshin Gangotri, Antarctica. Prolonged residency in Antarctica did not
      alter GH levels because mean GH values during Austral summer and Austral winter
      were not significantly different from the New Delhi values. Compared with GH, the
      insulin levels during March, April, and June were found to be significantly lower
      than the New Delhi values. In Antarctica, the insulin levels in March, April,
      May, June, July, and August were also found to be significantly lower than the
      December values. This decline in insulin in Antarctica might be important in
      increasing substrate availability for heat production by facilitating lipolysis
      and hepatic glucose output.

PMID- 9639554
TI  - Prothymosin alpha is a chromatin-remodelling protein in mammalian cells.
AB  - Prothymosin alpha (ProTalpha) is an abundant mammalian acidic nuclear protein
      whose expression is related to cell proliferation. Here we report that in HL-60
      cells overexpressing ProTalpha, the accessibility of micrococcal nuclease to
      chromatin is strongly increased. In the DNA ladder generated by the nuclease
      activity, the sizes of the mononucleosome (146 bp, the DNA fragment that is bound
      to the histone octamer) and its multimers correspond to nucleosomes lacking
      histone H1. The percentage of histone-H1-depleted chromatin (active chromatin) is
      also higher in the cells overexpressing ProTalpha. On the basis of these and
      previous findings, we propose a biological role for ProTalpha in the remodelling
      of chromatin fibres through its interaction with histone H1.

PMID- 9639555
TI  - The majority of human glutathione peroxidase type 5 (GPX5) transcripts are
      incorrectly spliced: implications for the role of GPX5 in the male reproductive
      tract.
AB  - An epididymis-specific, secretory glutathione peroxidase (GPX5) has been proposed
      previously to play a role in protecting mammalian sperm membranes from the
      deleterious effects of lipid peroxidation, which, if not contained, can lead to
      reduced fertilizing capacity. Here we report the cDNA cloning of human GPX5 and
      show that the majority of transcripts contain a 118 nt frame-shifting deletion,
      arising, most likely, from inappropriate excision of exon 3 during processing.
      Antisera raised against recombinant human GPX5 cross-reacted with rat and macaque
      (Macaca fascicularis) epididymal proteins of the size expected for full-length,
      active GPX5. However, no similar reactivity could be demonstrated in any of the
      human samples tested.

PMID- 9639556
TI  - Differential activation of stress-activated protein kinase kinases SKK4/MKK7 and
      SKK1/MKK4 by the mixed-lineage kinase-2 and mitogen-activated protein kinase
      kinase (MKK) kinase-1.
AB  - Overexpression of the protein kinases mixed-lineage kinase-2 (MLK2) or mitogen
      activated protein kinase (MAPK) kinase kinase-1 (MEKK1) is known to trigger the
      activation of stress-activated protein kinase (SAPK1)/c-Jun N-terminal kinase
      (JNK). Here we demonstrate that MLK2 activates SAPK kinase-1 (SKK1)/MAPK kinase 4
      (MKK4) and SKK4/MKK7, the two known direct activators of SAPK1/JNK (both in
      transfection studies and in vitro). In contrast, MEKK1 activates SKK1/MKK4 more
      efficiently than MLK2, but barely activates SKK4/MKK7. Since SKK4/MKK7 (but not
      SKK1/MKK4) is activated by interleukin-1 and tumour necrosis factor in several
      cells and tissues, we suggest that MEKK1 does not mediate the activation of
      SKK4/MKK7 and SAPK1/JNK induced by these pro-inflammatory cytokines. MLK2 and
      MEKK1 also activated SKK2/MKK3 and SKK3/MKK6, the direct upstream activators of
      SAPK2a/p38.

PMID- 9639557
TI  - Elucidation of a promoter activity that directs the expression of acetyl-CoA
      carboxylase alpha with an alternative N-terminus in a tissue-restricted fashion.
AB  - Previous studies in rats and humans have demonstrated that acetyl-CoA carboxylase
      alpha (ACC-alpha), the principal ACC isoenzyme in lipogenic tissues, is
      transcribed from two promoters, PI and PII, that operate in a tissue-specific
      fashion. Each promoter gives rise to ACC-alpha mRNA isoforms that differ in their
      5' untranslated regions but essentially encode the same protein product. In the
      present study we demonstrate that such a pattern of promoter usage is evident in
      sheep tissues but in addition we have detected the expression of a novel ACC
      alpha mRNA isoform that is expressed in a variety of tissues including kidney,
      lung, liver and mammary gland, where it is markedly induced during lactation.
      This novel transcript differs from the previously described ACC-alpha mRNA in
      that exon 5, the primary coding exon in both PI and PII transcripts, is replaced
      by a 424-nt sequence that seems to represent the 5' terminus of the mRNA. The 424
      nt sequence encodes a 17-residue N-terminal region as the N-terminal residue in
      the deduced sequence is a methionine flanked by several in-frame stop codons. The
      5' terminal 424 nt are present as a single exon, which we have termed exon 5A, in
      the sheep ACC-alpha gene and this is located approx. 15 kb downstream of exon 5
      and 5 kb upstream of exon 6. A 1.5 kb HindIII-BglII fragment encompassing the 5'
      terminus and sequence immediately upstream of exon 5A demonstrates promoter
      activity when transiently transfected into HepG2 cells and HC11 mouse mammary
      cells and this is markedly enhanced when insulin is present in the culture
      medium. Promoter activity is also evident in primary sheep mammary epithelial
      cells. These results demonstrate the presence of a third promoter, PIII, in the
      ACC-alpha gene that results in the tissue-restricted expression of an ACC
      isoenzyme.

PMID- 9639558
TI  - Functional characterization of a recombinant form of the C-terminal, globular
      head region of the B-chain of human serum complement protein, C1q.
AB  - The first step in the activation of the classical pathway of the complement
      system by immune complexes involves the binding of the six globular heads of C1q
      to the Fc regions of IgG or IgM. The globular heads of C1q are located C-terminal
      to the six triple-helical stalks present in the molecule; each head is considered
      to be composed of the C-terminal halves (3x136 residues) of one A-, one B- and
      one C-chain. It is not known if the C-terminal globular regions, present in each
      of the three types of chain, are independently folded modules (with each chain
      having distinct binding properties towards immunoglobulins) or whether the
      different binding functions of C1q are dependent upon a globular structure which
      relies on contributions from all three chains. As a first step towards addressing
      this question, we have expressed the globular head region (residues 87-226) of
      the C1q B-chain (ghB) as a soluble fusion protein with maltose-binding protein
      (MBP) in Escherichia coli. The affinity purified fusion protein, designated MBP
      ghB, behaved as a dimer on gel filtration and bound preferentially to aggregated
      IgG rather than to IgM. It could also inhibit C1q-dependent haemolysis of both
      IgG- and IgM-sensitized erythrocytes. After its release from MBP, by use of
      Factor Xa, the free ghB exhibited a tendency to aggregate and come out of
      solution. Since MBP is known to be a monomeric molecule, the dimerization of the
      MBP-ghB fusion polypeptide is probably brought about by the ghB region, perhaps
      through hydrophobic interactions within the ghB region. The functional behaviour
      of MBP-ghB indicates that the globular regions of C1q may adopt a modular
      organization, i.e. each globular head of C1q may be composed of three
      structurally and functionally independent domains, thus retaining multivalency in
      the form of a heterotrimer.

PMID- 9639559
TI  - Characterization of authentic recombinant pea-seed lipoxygenases with distinct
      properties and reaction mechanisms.
AB  - The two major isoforms of lipoxygenase (LOX-2 and LOX-3) from pea (Pisum sativum
      L. cv. Birte) seeds have been cloned and expressed from full-length cDNAs as
      soluble, active, non-fusion proteins in Escherichia coli. A comparison of both
      isoforms purified to apparent homogeneity from E. coli and pea seeds has
      confirmed the authenticity of the recombinant products and established the
      properties of the native enzymes. Despite 86% similarity at the amino acid
      sequence level, the enzymes have distinct properties. They have been
      characterized in terms of specific activity, Fe content, optimum pH, substrate
      and product specificity, apparent Km and Vmax for the preferred substrate,
      linoleic acid, and interfacial behaviour with linoleic acid. We have used this
      evidence, in addition to EPR spectroscopy of the hydroperoxide-activated enzymes
      and estimates of kcat/Km, to propose different reaction mechanisms for linoleic
      acid oxidation for the two isoforms. The differences relate primarily to carbonyl
      production from linoleic acid for which we propose a mechanism. This implicates
      the release of a peroxyl radical in an aerobic hydroperoxidase reaction, as the
      source of the carbonyl compounds formed by dismutation of the liberated peroxyl
      radical.

PMID- 9639560
TI  - Cytotoxic effect of HIV-1 coat glycoprotein gp120 on human neuroblastoma CHP100
      cells involves activation of the arachidonate cascade.
AB  - HIV type-1 (HIV-1) coat glycoprotein gp120 causes necrotic death in human
      neuroblastoma CHP100 cells. Here, we investigated the possible role of the
      arachidonate cascade and membrane peroxidation in gp120-induced cell necrosis. It
      is shown that gp120 increases the intracellular concentrations of prostaglandin
      E2 and leukotriene B4 by up-regulating the activity and expression of the
      arachidonate-metabolizing enzymes prostaglandin H synthase and 5-lipoxygenase
      respectively. Consistent with this observation, selective inhibitors of
      prostaglandin H synthase (i.e. indomethacin) and 5-lipoxygenase (i.e. MK886 and
      caffeic acid) protected CHP100 cells against gp120-induced necrosis. Treatment
      with gp120 also enhanced membrane lipid peroxidation and this may be implicated
      in the execution of cell damage. Interestingly, incubation with exogenous nitric
      oxide (NO) mimicked the effects of gp120 on necrotic death of CHP100 cells and
      activation of prostaglandin H synthase and 5-lipoxygenase. This suggests that NO
      might participate in the mechanism by which gp120 activates the arachidonate
      cascade.

PMID- 9639561
TI  - The first high-mobility-group box of upstream binding factor assembles across
      over DNA junction by basic residues.
AB  - Upstream binding factor (UBF) is a eukaryotic RNA polymerase I-specific
      transcription factor. Its predominant DNA-binding motif, ubfHMG box 1, preserves
      DNA assembling activity that can bind two or more DNA duplexes simultaneously to
      form a crossover DNA junction. Here we investigate the basis of crossover DNA
      assembling activity of ubfHMG box 1 by extensive mutagenesis analyses and
      mobility shift assay. Although the ubfHMG box 1 preserves a high mobility group
      (HMG) core structure, changing a number of the consensus hydrophobic and aromatic
      residues to alanine did not inhibit its crossover-assembling activity. This
      indicates that these residues do not directly participate in protein-DNA
      interaction. However, altering a series of basic residues in the helices 1 and 2
      regions or the N-terminal extended strand of the ubfHMG box 1 motif had severe
      effects on DNA-assembling activity; however, certain non-specific DNA binding
      activity still remained. This suggests that the ubfHMG box 1 motif might
      extensively contact the backbone of a crossover junction through its multiple
      basic residues. Mutating a hydrophobic residue in the terminal dimerization
      domain inhibited the association of truncated Xenopus UBF, but had little effect
      on its crossover-assembling activity. This indicates that the UBF-crossover DNA
      complex is not established by the association of individual DNA-bound peptides.

PMID- 9639562
TI  - Differential effects of phorbol ester on growth and protein kinase C isoenzyme
      regulation in human hepatoma Hep3B cells.
AB  - PMA has both mitogenic and antiproliferative effects on human hepatoma Hep3B
      cells. In response to low PMA concentration (10 nM), Hep3B cells displayed an
      increasing proliferation potentiation. At high PMA concentration (1 microM) Hep3B
      cells exhibited modest cytostatic effects. Determinations of protein kinase C
      (PKC) activity in PMA-treated cells revealed that alterations in PKC activity are
      associated with proliferative capacity. The decrease in PKC activity mediated by
      a high dose of PMA was accompanied by cell growth inhibition. Increases in PKC
      activity mediated by a low dose of PMA were consistent with proliferation
      stimulation. Immunoblot analysis showed that there are at least six PKC
      isoenzymes: alpha, delta, epsilon, mu, zeta and iota/lambda, constitutively
      expressed in Hep3B cells. Cellular fractionation and immunocytochemical staining
      results demonstrated that both 10 nM and 1 microM PMA treatments induced a marked
      translocation of PKC-alpha from cytosol to membrane or nuclear fraction within 5
      30 min. At the same time PKC-delta and epsilon were translocated from the
      membrane to nuclear fraction. In addition, prolonged treatment with 1 microM PMA,
      but not with 10 nM PMA, selectively mediated the down-regulation of these three
      PKC isoenzymes. The distinct effects of different concentrations of PMA on cell
      proliferation and PKC-alpha, delta and epsilon isoenzyme modulation support the
      involvement of these three PKC isotypes in the mechanism of action of Hep3B cells
      in cell growth events.

PMID- 9639563
TI  - Changing nucleosome positions in vivo through modification of the DNA rotational
      information.
AB  - The effects of the rotational information of DNA in determining the in vivo
      localization of nucleosomal core particles (ncps) have been studied in the
      Saccharomyces cerevisiae 5 S rRNA repeat gene. The distribution of the phased
      series of flexibility signals present in this DNA has been altered by inserting
      in its centre a 25 bp tract. The effects of such alteration on the in vivo
      distribution of the helically phased, alternatively located ncps have been
      determined relative to a reference 21 bp insertion mutant. The results show that
      the answers provided in vitro and in vivo by the yeast 5 S rRNA gene sequence to
      specific modifications of the DNA rotational frame are similar, thus pointing to
      the relevance of DNA rotational information in vivo.

PMID- 9639564
TI  - Structural and functional effect of Trp-62-->Gly and Asp-101-->Gly substitutions
      on substrate-binding modes of mutant hen egg-white lysozymes.
AB  - In order to clarify the structural role of subsite B of hen egg-white lysozyme in
      hydrolytic activity towards a carbohydrate substrate, we analysed the structures
      of Trp-62-->Gly and Asp-101-->Gly mutant hen lysozymes, which have no side chain
      at positions 62 or 101, complexed with a substrate analogue, (N-acetyl-d
      glucosamine)3 [(GlcNAc)3], using X-ray crystallography. The overall protein
      structures in the mutant lysozyme complexes were almost identical to those in the
      wild type. In the crystals of all the mutant complexes, the (GlcNAc)3 molecule,
      which is an inhibitor of wild-type lysozyme, had no inhibitory effect, but was
      hydrolysed as a substrate. One of the products, (GlcNAc)2, the reducing end of
      which is an alpha-anomer, was bound in an unproductive binding mode, protruding
      from the active-site cleft, and was able to act as an inhibitor. Hydrolysis of
      the synthetic substrate by the mutants occurred in a beta-anomer-retaining
      manner, and so the alpha-anomer product was converted from the beta-anomer
      product. Thus the interactions of Asp-101 and Trp-62 in subsite B are not
      essential for the catalytic mechanism, but co-operatively enhance the affinity of
      the substrate in the productive binding mode, other than the inhibitor in the
      unproductive mode.

PMID- 9639565
TI  - Nuclear factor 1 regulates the distal silencer of the human PIT1/GHF1 gene.
AB  - Here we report the characterization of 12 kb genomic DNA upstream of the human
      PIT1/GHF1 promoter. Different regions involved in the modulation of human
      PIT1/GHF1 gene expression were defined by transient transfection studies. Two
      regions, one proximal (-7.1/-2. 3) and one distal (-11.8/-10.9), presented an
      enhancer activity in pituitary cells when placed upstream of the SV40 promoter.
      The 0.9 kb distal region was analysed further and found to decrease the basal
      transcriptional activity of the human PIT1/GHF1 minimal promoter, indicating that
      this region behaves as a silencer for its own promoter. Three Pit-1/GHF-1-binding
      sites and two ubiquitous nuclear factor 1 (NF-1)-binding sites were identified by
      DNase I footprinting in the distal regulatory region. Deletion analysis indicated
      that NF-1 or NF-1-related protein(s) participate in the down-regulation of human
      PIT1/GHF1 gene expression by interacting with an NF-1-binding site within the
      distal regulatory region.

PMID- 9639566
TI  - Alteration of zif268 zinc-finger motifs gives rise to non-native zinc-co
      ordination sites but preserves wild-type DNA recognition.
AB  - Zinc fingers are among the major structural motifs found in proteins that are
      involved in eukaryotic gene regulation. Many of these zinc-finger domains are
      involved in DNA binding. This study investigated whether the zinc-co-ordinating
      (Cys)2(His)2 motif found in the three zinc fingers of zif268 could be replaced by
      a (Cys)4 motif while still preserving DNA recognition. (Cys)2(His)2-to-(Cys)4
      mutations were generated in each of the three zinc fingers of zif268
      individually, as well as in fingers 1 and 3, and fingers 2 and 3 together.
      Whereas finger 1 and finger 3 tolerate the switch, such an alteration in finger 2
      renders the polypeptide incapable of DNA recognition. The protein-DNA interaction
      was examined in greater detail by using a methylation-interference assay. The
      mutant polypeptides containing the (Cys)4 motif in fingers 1 or 3 recognize DNA
      in a manner identical to the wild-type protein, suggesting that the (Cys)4 motif
      appears to give rise to a properly folded finger. Additional results indicate
      that a zif268 variant containing a (Cys)2(His)(Ala) arrangement in finger 1 is
      also capable of DNA recognition in a manner identical to the wild-type
      polypeptide. This appears to be the first time that such alterations, in the
      context of an intact DNA-binding domain, have still allowed for specific DNA
      recognition. Taken together, the work presented here enhances our understanding
      of the relationship between metal ligation and DNA-binding by zinc fingers.

PMID- 9639567
TI  - The tumour necrosis factor-sensitive pool of sphingomyelin is resynthesized in a
      distinct compartment of the plasma membrane.
AB  - Sphingomyelin (SM) biosynthesis is believed to occur in the early Golgi
      apparatus, plasma membrane and recycling endosomes. In the present study, the
      localization of the SM synthesis that follows its hydrolysis upon activation of
      the SM signal-transduction pathway was investigated in human skin fibroblasts
      treated with tumour necrosis factor (TNF) alpha. After TNFalpha-induced
      degradation, the intracellular SM levels returned to baseline levels within 30-60
      min in cells treated at 37 degrees C. Pretreatment or co-incubation of cells with
      bacterial sphingomyelinase or phospholipase C, decreasing the SM and
      phosphatidylcholine content in the external leaflet of the plasma membrane
      respectively, did not inhibit SM resynthesis. However, SM resynthesis was not
      observed when TNFalpha-treated cells were continuously exposed to exogenous
      sphingomyelinase, suggesting that under these particular conditions the
      resynthesized SM becomes accessible to the enzyme. Furthermore, whereas
      inhibition of vesicular traffic/endocytosis at 4 degrees C blocked exoplasmic SM
      resynthesis, it did not alter SM resynthesis in TNFalpha-treated fibroblasts,
      negating the role of endosomes and the Golgi apparatus. This was further
      evidenced by the finding that after SM resynthesis, TNFalpha was again able to
      promote SM turnover, even at 4 degrees C. In addition, when the exoplasmic
      leaflet SM was hydrolysed by treating fibroblasts with bacterial
      sphingomyelinase, resynthesis of SM occurred at 37 degrees C much more slowly
      than after TNFalpha treatment. These findings support strongly the conclusion
      that the SM, which is resynthesized after TNFalpha-induced hydrolysis, resides in
      the cytosolic leaflet of the plasma membrane, and that the process involved in
      this resynthesis displays characteristics different from those of the previously
      described SM synthases.

PMID- 9639568
TI  - Evidence that the conformation of unliganded human plasminogen is maintained via
      an intramolecular interaction between the lysine-binding site of kringle 5 and
      the N-terminal peptide.
AB  - Human Glu-plasminogen adopts at least three conformations that provide a means
      for regulating the specificity of its activation in vivo. It has been proposed
      previously that the closed (alpha) conformation of human Glu-plasminogen is
      maintained through physical interaction of the kringle 5 domain and a lysine
      residue within the N-terminal peptide (NTP). To examine this hypothesis, site
      directed mutagenesis was used to generate variant proteins containing
      substitutions either for aspartic acid residues within the anionic centre of the
      kringle 5 domain or for conserved lysine residues within the NTP. Size-exclusion
      HPLC and rates of plasminogen activation by urokinase-type plasminogen activator
      were used to determine the conformational states of these variants. Variants with
      substitutions within the kringle 5 lysine-binding site demonstrated extended
      conformations, as did variants with alanine substitutions for Lys50 and Lys62. In
      contrast, molecules in which NTP residues Lys20 or Lys33 were replaced were shown
      to adopt closed conformations. We conclude that the lysine-binding site of
      kringle 5 is involved in maintaining the closed conformation of human Glu
      plasminogen via an interaction with the NTP, probably through Lys50 and/or Lys62.
      These conclusions advance the current model for the initial stages of
      fibrinolysis during which fibrin is thought to compete with the NTP for the
      kringle 5 lysine-binding site.

PMID- 9639569
TI  - L-Mandelate dehydrogenase from Rhodotorula graminis: cloning, sequencing and
      kinetic characterization of the recombinant enzyme and its independently
      expressed flavin domain.
AB  - The l-mandelate dehydrogenase (L-MDH) from the yeast Rhodotorula graminis is a
      mitochondrial flavocytochrome b2 which catalyses the oxidation of mandelate to
      phenylglyoxylate coupled with the reduction of cytochrome c. We have used the N
      terminal sequence of the enzyme to isolate the gene encoding this enzyme using
      the PCR. Comparison of the genomic sequence with the sequence of cDNA prepared by
      reverse transcription PCR revealed the presence of 11 introns in the coding
      region. The predicted amino acid sequence indicates a close relationship with the
      flavocytochromes b2 from Saccharomyces cerevisiae and Hansenula anomala, with
      about 40% identity to each. The sequence shows that a key residue for substrate
      specificity in S. cerevisiae flavocytochrome b2, Leu-230, is replaced by Gly in L
      MDH. This substitution is likely to play an important part in determining the
      different substrate specificities of the two enzymes. We have developed an
      expression system and purification protocol for recombinant L-MDH. In addition,
      we have expressed and purified the flavin-containing domain of L-MDH
      independently of its cytochrome domain. Detailed steady-state and pre-steady
      state kinetic investigations of both L-MDH and its independently expressed flavin
      domain have been carried out. These indicate that L-MDH is efficient with both
      physiological (cytochrome c, kcat=225 s-1 at 25 degrees C) and artificial
      (ferricyanide, kcat=550 s-1 at 25 degrees C) electron acceptors. Kinetic isotope
      effects with [2-2H]mandelate indicate that H-C-2 bond cleavage contributes
      somewhat to rate-limitation. However, the value of the isotope effect erodes
      significantly as the catalytic cycle proceeds. Reduction potentials at 25 degrees
      C were measured as -120 mV for the 2-electron reduction of the flavin and -10 mV
      for the 1-electron reduction of the haem. The general trends seen in the kinetic
      studies show marked similarities to those observed previously with the
      flavocytochrome b2 (L-lactate dehydrogenase) from S. cerevisiae.

PMID- 9639570
TI  - Re-design of Saccharomyces cerevisiae flavocytochrome b2: introduction of L
      mandelate dehydrogenase activity.
AB  - Flavocytochrome b2 from Saccharomyces cerevisiae is an l-lactate dehydrogenase
      which exhibits only barely detectable activity levels towards another 2
      hydroxyacid, l-mandelate. Using protein engineering methods we have altered the
      active site of flavocytochrome b2 and successfully introduced substantial
      mandelate dehydrogenase activity into the enzyme. Changes to Ala-198 and Leu-230
      have significant effects on the ability of the enzyme to utilize l-mandelate as a
      substrate. The double mutation of Ala-198-->Gly and Leu-230-->Ala results in an
      enzyme with a kcat value (25 degrees C) with L-mandelate of 8.5 s-1, which
      represents an increase of greater than 400-fold over the wild-type enzyme.
      Perhaps more significantly, the mutant enzyme has a catalytic efficiency (as
      judged by kcat/Km values) that is 6-fold higher with l-mandelate than it is with
      L-lactate. Closer examination of the X-ray structure of S. cerevisiae
      flavocytochrome b2 led us to conclude that one of the haem propionate groups
      might interfere with the binding of L-mandelate at the active site of the enzyme.
      To test this idea, the activity with l-mandelate of the independently expressed
      flavodehydrogenase domain (FDH), was examined and found to be higher than that
      seen with the wild-type enzyme. In addition, the double mutation of Ala-198-->Gly
      and Leu-230-->Ala introduced into FDH produced the greatest mandelate
      dehydrogenase activity increase, with a kcat value more than 700-fold greater
      than that seen with the wild-type holoenzyme. In addition, the enzyme efficiency
      (kcat/Km) of this mutant enzyme was more than 20-fold greater with L-mandelate
      than with l-lactate. We have therefore succeeded in constructing an enzyme which
      is now a better mandelate dehydrogenase than a lactate dehydrogenase.

PMID- 9639571
TI  - Thrombin stimulates fibroblast procollagen production via proteolytic activation
      of protease-activated receptor 1.
AB  - Thrombin is a multifunctional serine protease that has a crucial role in blood
      coagulation. It is also a potent mesenchymal cell mitogen and chemoattractant and
      might therefore have an important role in the recruitment and local proliferation
      of mesenchymal cells at sites of tissue injury. We hypothesized that thrombin
      might also affect the deposition of connective tissue proteins at these sites by
      directly stimulating fibroblast procollagen production. To address this
      hypothesis, the effect of thrombin on procollagen production and gene expression
      by human foetal lung fibroblasts was assessed over 48 h. Thrombin stimulated
      procollagen production at concentrations of 1 nM and above, with maximal
      increases of between 60% and 117% at 10 nM thrombin. These effects of thrombin
      were, at least in part, due to increased steady-state levels of alpha1(I)
      procollagen mRNA. They could furthermore be reproduced with thrombin receptor
      activating peptides for the protease-activated receptor 1 (PAR-1) and were
      completely abolished when thrombin was rendered proteolytically inactive with the
      specific inhibitors d-Phe-Pro-ArgCH2Cl and hirudin, indicating that thrombin is
      mediating these effects via the proteolytic activation of PAR-1. These results
      suggest that thrombin might influence the deposition of connective tissue
      proteins during normal wound healing and the development of tissue fibrosis by
      stimulating fibroblast procollagen production.

PMID- 9639572
TI  - Assembly of flammutoxin, a cytolytic protein from the edible mushroom Flammulina
      velutipes, into a pore-forming ring-shaped oligomer on the target cell.
AB  - Flammutoxin has been previously isolated as a cardiotoxic and cytolytic
      polypeptide of 22 or 32 kDa from the fruiting bodies of the edible mushroom
      Flammulina velutipes. In the present study, we purified flammutoxin as a single
      haemolytic protein of 31 kDa and studied the mode of its cytolytic action. (1)
      Flammutoxin caused efflux of potassium ions from human erythrocytes and swelling
      of the cells before haemolysis. (2) Flammutoxin did not lyse human erythrocytes
      in the presence of non-electrolytes with hydrodynamic diameters of >5.0 nm,
      although it caused leakage of potassium ions and swelling of the cells under the
      same conditions. (3) Experiments including solubilization of cell-bound toxin
      with 2% (w/v) SDS at 20 degrees C and subsequent Western immunoblots showed that
      flammutoxin formed a band corresponding to 180 kDa under the conditions where it
      lysed erythrocytes. (4) Electron microscopy of flammutoxin-treated human
      erythrocytes revealed the presence of a ring-shaped structure with outer and
      inner diameters of 10 and 5 nm, respectively, on the cells. (5) A ring-shaped
      toxin oligomer of the same dimensions was solubilized from the toxin-treated
      human erythrocytes with 2% (w/v) SDS at 20 degrees C and isolated by a sucrose
      gradient ultracentrifugation. These data indicated that flammutoxin assembles
      into a ring-shaped oligomer possessing a hydrophilic pore of 4-5 nm on target
      cells.

PMID- 9639573
TI  - cAMP-specific phosphodiesterase HSPDE4D3 mutants which mimic activation and
      changes in rolipram inhibition triggered by protein kinase A phosphorylation of
      Ser-54: generation of a molecular model.
AB  - Ser-13 and Ser-54 were shown to provide the sole sites for the protein kinase A
      (PKA)-mediated phosphorylation of the human cAMP-specific phosphodiesterase
      isoform HSPDE4D3. The ability of PKA to phosphorylate and activate HSPDE4D3 was
      mimicked by replacing Ser-54 with either of the negatively charged amino acids,
      aspartate or glutamate, within the consensus motif of RRES54. The PDE4 selective
      inhibitor rolipram ?4-[3-(cyclopentoxy)-4-methoxyphenyl]-2-pyrrolidone? inhibited
      both PKA-phosphorylated HSPDE4D3 and the Ser-54-->Asp mutant, with an IC50 value
      that was approximately 8-fold lower than that seen for the non-PKA-phosphorylated
      enzyme. Lower IC50 values for inhibition by rolipram were seen for a wide range
      of non-activated residue 54 mutants, except for those which had side-chains able
      to serve as hydrogen-bond donors, namely the Ser-54-->Thr, Ser-54-->Tyr and Ser
      54-->Cys mutants. The Glu-53-->Ala mutant exhibited an activity comparable with
      that of the PKA phosphorylated native enzyme and the Ser-54-->Asp mutant but, in
      contrast to the native enzyme, was insensitive to activation by PKA, despite
      being more rapidly phosphorylated by this protein kinase. The activated Glu-53-
      >Ala mutant exhibited a sensitivity to inhibition by rolipram which was unchanged
      from that of the native enzyme. The double mutant, Arg-51-->Ala/Arg-52-->Ala,
      showed no change in either enzyme activity or rolipram inhibition from the native
      enzyme and was incapable of providing a substrate for PKA phosphorylation at Ser
      54. No difference in inhibition by dipyridamole was seen for the native enzyme
      and the Ser-54-->Asp and Ser-54-->Ala mutants. A model is proposed which
      envisages that phosphorylation by PKA triggers at least two distinct
      conformational changes in HSPDE4D3; one of these gives rise to enzyme activation
      and another enhances sensitivity to inhibition by rolipram. Activation of
      HSPDE4D3 by PKA-mediated phosphorylation is suggested to involve disruption of an
      ion-pair interaction involving the negatively charged Glu-53. The increase in
      susceptibility to inhibition by rolipram upon PKA-mediated phosphorylation is
      suggested to involve the disruption of a hydrogen-bond involving the side-chain
      hydroxy group of Ser-54.

PMID- 9639574
TI  - Targeting and assembly of the oxoglutarate carrier: general principles for
      biogenesis of carrier proteins of the mitochondrial inner membrane.
AB  - We have studied the targeting and assembly of the 2-oxoglutarate carrier (OGC),
      an integral inner-membrane protein of mitochondria. The precursor of OGC,
      synthesized without a cleavable presequence, is transported into mitochondria in
      an ATP- and membrane potential-dependent manner. Import of the mammalian OGC
      occurs efficiently into both mammalian and yeast mitochondria. Targeting of OGC
      reveals a clear dependence on the mitochondrial surface receptor Tom70 (the 70
      kDa subunit of the translocase of the outer mitochondrial membrane), whereas a
      cleavable preprotein depends on Tom20 (the 20 kDa subunit), supporting a model of
      specificity differences of the receptors and the existence of distinct targeting
      pathways to mitochondria. The assembly of minute amounts of OGC imported in vitro
      to the dimeric form can be monitored by blue native electrophoresis of digitonin
      lysed mitochondria. The assembly of mammalian OGC and fungal ADP/ATP carrier
      occurs with high efficiency in both mammalian and yeast mitochondria. These
      findings indicate a dynamic behaviour of the carrier dimers in the mitochondrial
      inner membrane and suggest a high conservation of the assembly reactions from
      mammals to fungi.

PMID- 9639575
TI  - Membrane type 1 matrix metalloproteinase (MT1-MMP) cleaves the recombinant
      aggrecan substrate rAgg1mut at the 'aggrecanase' and the MMP sites.
      Characterization of MT1-MMP catabolic activities on the interglobular domain of
      aggrecan.
AB  - The recent detection of membrane type 1 matrix metalloproteinase (MT1-MMP)
      expression in human articular cartilage [Buttner, Chubinskaya, Margerie, Huch,
      Flechtenmacher, Cole, Kuettner, and Bartnik (1997) Arthritis Rheum. 40, 704-709]
      prompted our investigation of MT1-MMP's catabolic activity within the
      interglobular domain of aggrecan. For these studies we used rAgg1mut, a mutated
      form of the recombinant fusion protein (rAgg1) that has been used as a substrate
      to monitor 'aggrecanase' catabolism in vitro [Hughes, Buttner, Eidenmuller,
      Caterson and Bartnik (1997) J. Biol. Chem. 272, 20269-20274]. The rAgg1 was
      mutated (G332 to A) to avoid the generation of a splice variant seen with the
      original genetic construct, which gave rise to heterogeneous glycoprotein
      products. This mutation yielded a homogeneous recombinant product. Studies in
      vitro with retinoic acid-stimulated rat chondrosarcoma cells indicated that the
      rAgg1mut substrate was cleaved at the 'aggrecanase' site equivalent to Glu373
      Ala374 (human aggrecan sequence enumeration) in its interglobular domain sequence
      segment. The differential catabolic activities of the recombinant catalytic
      domain (cd) of MT1-MMP and matrix metalloproteinases (MMPs) 3 and 8 were then
      compared by using this rAgg1mut as a substrate. Coomassie staining of rAgg1mut
      catabolites separated by SDS/PAGE showed similar patterns of degradation with all
      three recombinant enzymes. However, comparative immunodetection analysis, with
      neoepitope antibodies BC-3 (anti-ARGS...) and BC-14 (anti-FFGV...) to distinguish
      between 'aggrecanase' and MMP-generated catabolites, indicated that the catalytic
      domain of MT1-MMP exhibited strong 'aggrecanase' activity, cdMMP-8 weak activity
      and cdMMP-3 no activity. In contrast, cdMMP-3 and cdMMP-8 led to strongly BC-14
      reactive catabolic fragments, whereas cdMT1-MMP resulted in weak BC-14
      reactivity. N-terminal sequence analyses of the catabolites confirmed these
      results and also identified other potential minor cleavage sites within the
      interglobular domain of aggrecan. These results indicate that MT1-MMP is yet
      another candidate for 'aggrecanase' activity in vivo.

PMID- 9639576
TI  - Characterization of the monocarboxylate transporter 1 expressed in Xenopus laevis
      oocytes by changes in cytosolic pH.
AB  - Several laboratories have investigated monocarboxylate transport in a variety of
      cell types. The characterization of the cloned transporter isoforms in a suitable
      expression system is nevertheless still lacking. H+/monocarboxylate co-transport
      was therefore investigated in monocarboxylate transporter 1 (MCT1)-expressing
      Xenopus laevis oocytes by using pH-sensitive microelectrodes and [14C]lactate.
      Superfusion with lactate resulted in intracellular acidification of MCT1
      expressing oocytes, but not in non-injected control oocytes. The basic kinetic
      properties of lactate transport in MCT1-expressing oocytes were determined by
      analysing the rates of intracellular pH changes under different conditions. The
      results were in agreement with the known properties of the transporter, with
      respect to both the dependence on the lactate concentration and the external pH
      value. Besides lactate, MCT1 mediated the reversible transport of a wide variety
      of monocarboxylic acids including pyruvate, D,L-3-hydroxybutyrate, acetoacetate,
      alpha-oxoisohexanoate and alpha-oxoisovalerate, but not of dicarboxylic and
      tricarboxylic acids. The inhibitor alpha-cyano-4-hydroxycinnamate bound strongly
      to the transporter without being translocated, but could be displaced by the
      addition of lactate. In addition to changes in the intracellular pH, lactate
      transport also induced deviations from the resting membrane potential.

PMID- 9639577
TI  - Effects of dietary Pi on the renal Na+-dependent Pi transporter NaPi-2 in
      thyroparathyroidectomized rats.
AB  - Dietary Pi and parathyroid hormone (PTH) are two most important physiological and
      pathophysiological regulators of Pi re-absorption in the renal proximal tubule.
      Effects of dietary Pi on Na+/Pi co-transporter NaPi-2 were investigated in
      thyroparathyroidectomized (TPTX) rats. NaPi-2 protein and mRNA in the kidney
      cortex of TPTX rats were increased approximately 3.8- and 2.4-fold in amount
      respectively compared with those in the sham-operated animals. Administration of
      PTH to the TPTX rats resulted in a decrease in the amount of NaPi-2 protein, but
      not in the abundance of NaPi-2 mRNA. Deprivation of dietary Pi in the TPTX rats
      did not affect the amount of NaPi-2 mRNA and protein. In the Pi-deprived TPTX
      rats, feeding of a high-Pi diet resulted in marked decreases in Pi transport
      activity and the amount of NaPi-2 protein in the superficial nephrons.
      Immunohistochemical analysis demonstrated that administration of PTH to TPTX rats
      resulted in a decrease in NaPi-2 immunoreactivity from both superficial and
      juxtamedullary nephrons within 4 h. Switching TPTX animals from a low-Pi diet to
      the high-Pi diet decreased NaPi-2 immunoreactivity from superficial nephrons, but
      not from juxtamedullary nephrons, within 4 h. These results suggest that dietary
      Pi could regulate the amount of NaPi-2 protein in the superficial nephrons in a
      PTH-independent manner.

PMID- 9639578
TI  - A structural comparison of the colicin immunity proteins Im7 and Im9 gives new
      insights into the molecular determinants of immunity-protein specificity.
AB  - We report the first detailed comparison of two immunity proteins which, in
      conjunction with recent protein engineering data, begins to explain how these
      structurally similar proteins are able to bind and inhibit the endonuclease
      domain of colicin E9 (E9 DNase) with affinities that differ by 12 orders of
      magnitude. In the present work, we have determined the X-ray structure of the
      Escherichia coli colicin E7 immunity protein Im7 to 2.0 A resolution by molecular
      replacement, using as a trial model the recently determined NMR solution
      structure of Im9. Whereas the two proteins adopt similar four-helix structures,
      subtle structural differences, in particular involving a conserved tyrosine
      residue critical for E9 DNase binding, and the identity of key residues in the
      specificity helix, lie at the heart of their markedly different ability to bind
      the E9 DNase. Two other crystal structures were reported recently for Im7; in
      one, Im7 was a monomer and was very similar to the structure reported here,
      whereas in the other it was a dimer to which functional significance was
      assigned. Since this previous work suggested that Im7 could exist either as a
      monomer or a dimer, we used analytical ultracentrifugation to investigate this
      question further. Under a variety of solution conditions, we found that Im7 only
      ever exists in solution as a monomer, even up to protein concentrations of 15
      mg/ml, casting doubt on the functional significance of the crystallographically
      observed dimer. This work provides a structural framework with which we can
      understand immunity-protein specificity, and in addition we believe it to be the
      first successfully refined crystal structure solved by molecular replacement
      using an NMR trial model with less than 100% sequence identity.

PMID- 9639579
TI  - Secretory-granule dynamics visualized in vivo with a phogrin-green fluorescent
      protein chimaera.
AB  - To image the behaviour in real time of single secretory granules in
      neuroendocrine cells we have expressed cDNA encoding a fusion construct between
      the dense-core secretory-granule-membrane glycoprotein, phogrin (phosphatase on
      the granule of insulinoma cells), and enhanced green fluorescent protein (EGFP).
      Expressed in INS-1 beta-cells and pheochromocytoma PC12 cells, the chimaera was
      localized efficiently (up to 95%) to dense-core secretory granules (diameter 200
      1000 nm), identified by co-immunolocalization with anti-(pro-)insulin antibodies
      in INS-1 cells and dopamine beta-hydroxylase in PC12 cells. Using laser-scanning
      confocal microscopy and digital image analysis, we have used this chimaera to
      monitor the effects of secretagogues on the dynamics of secretory granules in
      single living cells. In unstimulated INS-1 beta-cells, granule movement was
      confined to oscillatory movement (dithering) with period of oscillation 5-10 s
      and mean displacement <1 microm. Both elevated glucose concentrations (30 mM),
      and depolarization of the plasma membrane with K+, provoked large (5-10 microm)
      saltatory excursions of granules across the cell, which were never observed in
      cells maintained at low glucose concentration. By contrast, long excursions of
      granules occurred in PC12 cells without stimulation, and occurred predominantly
      from the cell body towards the cell periphery and neurite extensions. Purinergic
      receptor activation with ATP provoked granule movement towards the membrane of
      PC12 cells, resulting in the transfer of fluorescence to the plasma membrane
      consistent with fusion of the granule and diffusion of the chimaera in the plasma
      membrane. These results illustrate the potential use of phogrin-EGFP chimeras in
      the study of secretory-granule dynamics, the regulation of granule-cytoskeletal
      interactions and the trafficking of a granule-specific transmembrane protein
      during the cycle of exocytosis and endocytosis.

PMID- 9639580
TI  - Alteration of the isoform composition of plasma-membrane-associated rat sperm
      alpha-L-fucosidase during late epididymal maturation: comparative
      characterization of the acidic and neutral isoforms.
AB  - In a previous study, evidence was provided for the presence of a novel plasma
      membrane-associated neutral-pH-optimum alpha-L-fucosidase in rat sperm. In the
      present study, rat sperm alpha-L-fucosidase was characterized during epididymal
      maturation. The pH 7 activity optimum of alpha-L-fucosidase and its subunit
      composition (one or two closely spaced immunoreactive protein bands of about 53+/
      2 kDa) did not appear to change during transit through the epididymis.
      Isoelectric focusing of alpha-L-fucosidase indicated the presence of a major
      isoform (B) with a pI near 7 in sperm from testis, caput, corpus and the proximal
      half of the cauda. alpha-L-Fucosidase from sperm from the distal half of the
      cauda, which contained a significant enrichment of sperm and alpha-L-fucosidase
      activity, contained isoform B and an additional minor isoform (A) with a pI near
      5.2. Isoform B and small amounts of isoform A were present in sperm from the vas
      deferens. The two fucosidase isoforms present in sperm from the distal cauda were
      separated by isoelectric focusing and comparatively characterized. They had
      similar pH-activity curves (with optima near pH 7) and comparable apparent KM
      values (0.4+/-0.04 mM) for 4-methylumbelliferyl alpha-l-fucopyranoside.
      Preincubation of the isoforms at different temperatures indicated that isoform A
      is considerably more thermostable than isoform B. Immunoprecipitation studies
      using polyclonal antibodies against human liver alpha-L-fucosidase indicated that
      approx. 90% of the enzymic activity for both isoforms was immunoprecipitable
      under conditions that immunoprecipitated essentially all the human liver enzyme.
      Neuraminidase treatment of sperm alpha-L-fucosidase from distal cauda (when
      compared with the appropriate heat-treated control) led to disappearance of
      isoform A and a concomitant increase in isoform B. The overall results suggest
      that isoform A is derived by sialylation of isoform B near the end of epididymal
      maturation.

PMID- 9639581
TI  - Sp3 regulates fas expression in lung epithelial cells.
AB  - By transducing an apoptotic signal in immune effector cells, Fas has been
      directly implicated in the control of immunological activity. Expression and
      functional results, however, have also suggested a role for Fas in regulating
      cell turnover in specific epithelial populations. To characterize factors
      responsible for Fas expression in epithelial cells, approximately 3 kb of the 5'
      flanking region of the mouse Fas gene was isolated. By rapid amplification of
      cDNA ends and primer extension, transcriptional start sites were identified
      within 50 bp upstream of the translation start site. Transient transfection of
      promoter-luciferase constructs in a mouse lung epithelial cell line, MLE-15,
      localized promoter activity to the first 77 bp of upstream sequence. By using a
      60 bp DNA probe (-18 to -77) in electrophoretic mobility-shift assays, three
      shifted complexes were found. Incubation with excess cold Sp1 oligonucleotide or
      an anti-Sp3 antibody inhibited complex formation. Site-directed mutagenesis of
      the Sp1 site resulted in 60-70% loss of promoter activity. In Drosophila SL-2
      cells, promoter activity was markedly increased by co-transfection of an Sp3
      expression construct. These results show that the Sp3 protein is involved in
      regulating Fas gene expression in lung epithelial cells.

PMID- 9639583
TI  - Identification of skatolyl hydroperoxide and its role in the peroxidase-catalysed
      oxidation of indol-3-yl acetic acid.
AB  - Indol-3-yl acetic acid (IAA, auxin) is a plant hormone whose degradation is a key
      determinant of plant growth and development. The first evidence for skatolyl
      hydroperoxide formation during the plant peroxidase-catalysed degradation of IAA
      has been obtained by electrospray MS. Skatolyl hydroperoxide degrades
      predominantly non-enzymically to oxindol-3-yl carbinol but in part enzymically
      into indol-3-yl methanol via a peroxidase cycle in which IAA acts as an electron
      donor. Skatolyl hydroperoxide is degradable by catalase. Horseradish peroxidase
      isoenzyme C (HRP-C) and anionic tobacco peroxidase (TOP) exhibit differences in
      their mechanisms of reaction. The insensitivity of the HRP-C-catalysed reaction
      to catalase is ascribed to the formation of HRP-C Compound III at the initiation
      step and its subsequent role in radical propagation. This is in contrast with the
      TOP-catalysed process in which skatolyl hydroperoxide has a key role. Indol-3-yl
      aldehyde is produced not via the peroxidase cycle but by catalysis involving
      ferrous peroxidase. Because indol-3-yl aldehyde is one of the main IAA-derived
      products identified in planta, we conclude that ferrous peroxidases participate
      in IAA catalytic transformations in vivo. A general scheme for peroxidase
      catalysed IAA oxidation is presented.

PMID- 9639582
TI  - Ca2+ modulation of cis-unsaturated fatty acid-induced mutant protein kinase C
      activity: indication of inhibitory Ca2+-binding site in protein kinase C-alpha.
AB  - The C2 domain in protein kinase C (PKC) is homologous to equivalent domains in a
      number of important cytoplasmic proteins. Except for its implied function in Ca2+
      and phospholipid binding, the precise role of this domain is not well understood.
      We examined the role of the C2 domain of PKC-alpha using a mutant enzyme in which
      80% of this domain has been deleted. This mutant can be activated by phospholipid
      and diacylglycerol, but is independent of Ca2+. In this regard, its
      characteristics are similar to those of the novel PKCs (nPKCs), consistent with
      the notion that the C2 domain of PKC confers its Ca2+ responsiveness. However,
      when the C2 deletion mutant is activated by cis-unsaturated fatty acid, the
      activity is strongly inhibited by Ca2+ at micromolar concentrations. The Ca2+
      inhibition is dose-dependent and is specific to cis-unsaturated fatty acids. The
      deletion mutant can also be activated synergistically by diacylglycerol and cis
      fatty acid, but again activation is inhibited by Ca2+. Our results indicate that
      a PKC lacking the C2 domain is Ca2+-responsive and there exists an additional
      site for Ca2+ that modulates the sensitivity of the enzyme to cis-unsaturated
      fatty acid but not to diacylglycerol. This modulatory Ca2+-binding site appears
      to be suppressed by the C2 domain because the presence of the domain reverses the
      direction of PKC activity induced by cis-unsaturated fatty acid. These results
      suggest that the modulatory Ca2+-binding site could act as a molecular switch
      selective for fatty acid activation by sensing the changes in the Ca2+ levels in
      a cell, serving a possible mechanism of differential activation of cPKC with a C2
      domain and nPKC lacking this domain.

PMID- 9639584
TI  - The electroneutral cation-chloride cotransporters.
AB  - Electroneutral cation-chloride cotransporters are widely expressed and perform a
      variety of physiological roles. A novel gene family of five members, encompassing
      a Na+-Cl- transporter, two Na+-K+-2Cl- transporters and two K+-Cl-
      cotransporters, encodes these membrane proteins; homologous genes have also been
      identified in a prokaryote and a number of lower eukaryotes. The cotransporter
      proteins share a common predicted membrane topology, with twelve putative
      transmembrane segments flanked by long hydrophilic N- and C-terminal cytoplasmic
      domains. The molecular identification of these transporters has had a significant
      impact on the study of their function, regulation and pathophysiology.

PMID- 9639585
TI  - Relaxation and activation of graviresponses in Paramecium caudatum.
AB  - The kinetics of gravitaxis and gravikinesis in Paramecium caudatum were
      investigated by employing (1) step transitions from normal gravity (1 g) to
      weightlessness (microgravity) and (2) turns of the experimental chambers from the
      horizontal to the vertical position at 1 g. The transition to microgravity left
      existing cell orientations unchanged. Relaxation of negative gravitaxis under
      microgravity took longer than 10 s and may be described by the time constant of
      the decay of orientation coefficients. Gravitaxis was started at 1 g by turning
      the experimental chamber from a horizontal to a vertical position. Gravitaxis
      activated rapidly during the turning procedure and relaxed to an intermediate
      level after the turning had stopped. Gravity-induced regulation of swimming speed
      (gravikinesis) at 1 g had reached a steady state after 1 min; at this point,
      gravikinesis counteracted the effects of sedimentation (negative gravikinesis). A
      step transition to microgravity initially reversed the sign of the gravikinesis
      (positive gravikinesis). The relaxation of this kinetic response was not
      completed during 10 s of microgravity. The data suggest that gravikinesis is
      functionally unrelated to gravitaxis and is strongly affected by the rate of
      change in acceleration. We present a model explaining why gravikinesis reverses
      sign upon the onset of a step from 1 g to microgravity.

PMID- 9639586
TI  - The electric image in weakly electric fish: physical images of resistive objects
      in Gnathonemus petersii.
AB  - The present study describes a measurement-based model of electric image
      generation in the weakly electric mormyrid fish Gnathonemus petersii.
      Measurements of skin impedance, internal resistivity and fish body dimensions
      have been used to generate an electrical-equivalent model of the fish and to
      calculate electrical images and equivalent dipole sources for elementary
      resistive objects. These calculations allow us to understand how exafferent and
      reafferent signals are sensed by electroreceptors. An object's electric image
      consists of the modulation of the transcutaneous voltage profile generated by the
      fish's own discharge. The results suggest a set of rules for electrolocation: (1)
      the side of the fish where modulation is larger indicates the side on which the
      object is situated; (2) the object's position in the electroreceptive field is
      indicated by the point of maximum modulation of the transcutaneous voltage; (3)
      the degree of focus of the image indicates the distance to the object. In
      addition, center-surround opposition originating at pre-receptor level is
      proposed. Both experimental measurements and modeling indicate that fish skin
      impedance is relatively low (400-11 000 <IMG src="/images/symbols/capomega.gif"
      WIDTH="13" HEIGHT="13" ALIGN="BOTTOM" NATURALSIZEFLAG="3">cm<SUP>2</SUP>) and
      mainly resistive. This low skin impedance appears to enhance the local electric
      organ discharge modulation, the center-surround effect, the signal-to-noise ratio
      for electrolocation and the active space for electrocommunication.

PMID- 9639587
TI  - A role of 5-HT2 receptors in the gill vasculature of the antarctic fish
      Pagothenia borchgrevinki.
AB  - This study was conducted to describe the cardiovascular responses to intra
      arterial injections of serotonin in the Antarctic fish Pagothenia borchgrevinki
      and to elucidate the underlying mechanisms. Immunohistochemistry was used to
      localise serotonin-containing cells within the gills. Simultaneous and continuous
      recordings of ventral and dorsal aortic blood pressure, heart rate and ventral
      aortic blood flow (cardiac output) were made using standard cannulation
      procedures in combination with Doppler flow measurement. An extracorporeal loop
      with an in-line oxygen electrode allowed continuous measurements of arterial
      oxygen pressure PaO2. Pre-branchial injection of serotonin (5-hydroxytryptamine,
      5-HT) or the 5-HT2 receptor agonist alpha-methylserotonin increased the branchial
      vascular resistance and ventral aortic pressure, while the 5-HT1 receptor agonist
      piperazine was without effect. The branchial vasoconstriction produced by
      serotonin injection was completely blocked by the 5-HT1/5-HT2 receptor antagonist
      methysergide and the branchial vasoconstriction produced by WIDTH="9" HEIGHT="12"
      ALIGN="BOTTOM" NATURALSIZEFLAG= alpha-methylserotonin injection was completely
      blocked by the specific 5-HT2 receptor antagonist LY53857. The results suggest
      that the 5-HT2 receptor alone mediates the branchial vasoconstriction. Serotonin
      also mediated a methysergide-sensitive reduction in PaO2, the reduction being
      greatest when the pre-injection PaO2 value was high. 5-HT-immunoreactive cells
      and nerve fibres were present within the gill tissues. All the 5-HT
      immunoreactive cells were located on the efferent side of the filaments, but 5-HT
      immunoreactive nerve fibres were found lining both of the branchial arteries. Our
      findings demonstrate a potential serotonergic control system for the gills in
      Pagothenia borchgrevinki. In contrast to its effects on the branchial
      vasculature, serotonin produced a methysergide-insensitive decrease in the
      systemic vascular resistance. However, neither the specific 5-HT1 nor 5-HT2
      receptor agonists produced a decrease in the resistance of the systemic
      vasculature. The nature of the serotonergic receptor(s) inducing vasodilation in
      teleost fish is uncertain.

PMID- 9639588
TI  - Digging in sand crabs: coordination of joints in individual legs.
AB  - Sand crabs use their multi-jointed legs to dig into sand. Combined movement and
      electromyogram (EMG) analyses showed that the pattern of intra-leg coordination
      in the legs of two sand crabs of different families (Blepharipoda occidentalis
      and Emerita analoga) is similar in legs 2 and 3, but very different in leg 4. For
      example, the sequence of proximal joint movements in legs 2 and 3 is elevation,
      retraction, depression and protraction (similar to backward walking in most
      decapods), but the sequence of proximal joint movements in leg 4 is elevation,
      protraction, retraction and depression (similar to forward walking). The
      synergies are the same during leg movements in sea water and in sand, suggesting
      that the same motor programme is used in both situations. At the transition from
      sea water into sand, however, both the frequency and amplitude of the EMG
      potentials increase, and the phasing of the motor output to leg 2 (and presumably
      leg 3) changes from proportional (both power and return strokes co-vary with
      period) to return stroke constant (power strokes co-vary much more with period
      than do return strokes). The motor output to leg 4 remains intermediate between
      proportional and return stroke constant in sea water and in sand. On the basis of
      the segmental specialisation of the motor patterns for the legs, we hypothesize
      that sand crab digging may be an evolutionary mosaic of disparate ancestral
      locomotor behaviours.

PMID- 9639589
TI  - Burrow ventilation in the tube-dwelling shrimp Callianassa subterranea (Decapoda:
      thalassinidea). I. Morphology and motion of the pleopods, uropods and telson.
AB  - The morphology of the pleopods, uropods and telson of the tube-dwelling shrimp
      Callianassa subterranea have been studied using dissection microscopy and
      scanning electron microscopy. The kinematics of these appendages were examined by
      motion analysis of macro-video recordings of ventilating shrimps in transparent
      artificial burrows. The pleopods show the usual crustacean biramous anatomy, but
      all segments are rostro-caudally flattened. The protopodite bears a triangular
      medially oriented endopodite and a scoop-shaped exopodite. The contralateral
      endopodites are linked by the appendix interna, ensuring a perfect phase
      relationship between contralateral pleopods. The outer rims of the exopodites are
      fringed with long fern-leaf-like plumose setae bearing flattened setules. These
      setae have very mobile joints and can be turned caudally. The slits between
      contralateral endopodites have rims of leaf-like setae as well. Setae of the same
      leaf-like type fringe the uropods, but these are non-motile. The telson has a
      narrow fringe of leaf-like setae, locally interrupted by long mechanoreceptory
      setae. A shrimp, wandering through the burrow or resting, holds its pleopods
      against the abdomen with the exopodites and their setal fringes retracted
      medially. The uropods are folded medially as well, probably to reduce the
      shrimp's drag. During ventilation, the uropods are extended against the tube
      wall, leaving only a small opening for flow ventral from the telson, and the
      pleopods beat at a frequency of approximately 1 Hz (0.9+/-0.2 Hz). Fourier
      analysis of pleopod kinematics showed that the motion pattern of the first flow
      generating pleopod pair (PP1) consisted mainly of the first harmonic (75 %) and
      to a lesser extent of the third harmonic (20 %), resulting in almost perfect
      sinusoidal motion. The motion patterns of PP2 and PP3 could be modelled by
      assigning pure sinusoids with a 120 degrees phase shift and a rostro-caudal
      ranking to the three pairs of pleopods.

PMID- 9639590
TI  - Burrow ventilation in the tube-dwelling shrimp callianassa subterranea (Decapoda:
      thalassinidea). II. The flow in the vicinity of the shrimp and the energetic
      advantages of a laminar non-pulsating ventilation current.
AB  - The ventilation flow in the vicinity of the pleopod-pumping thalassinid shrimp
      Callianassa subterranea in an artificial transparent burrow has been mapped using
      particle image velocimetry. The flow in the tube in front of the shrimp was
      unidirectional, laminar and steady, with a parabolic cross-sectional velocity
      profile. The mean flow velocity was 2.0+/-0.1 mm s-1. The flow passed the thorax
      of the shrimp along the lateral and ventral sides. Ventral to the abdomen, the
      flow was dominated by the metachronally oscillating pleopods. The water around a
      pleopod is accelerated caudally and ventrally during the power stroke, and
      decelerated to a much lesser extent during the recovery stroke owing to a
      reduction in pleopod area. On average, the flow ventral to the abdomen converged
      towards the small opening underneath the telson, simultaneously increasing in
      velocity. A jet with a core velocity of 18-20 mm s-1 entered the area behind the
      shrimp from underneath the telson. This caused a separation zone with backflow
      caudal to the telson. Owing to the high rates of shear, the jet diverged and re
      adjusted to a parabolic cross-sectional profile within 1-2 body lengths behind
      the shrimp, showing no traces of pulsation. The metachronal pleopod movements in
      combination with the increase in flow velocity at the constriction in the tube
      caused by the uropods and the telson probably prevented pulsation. The energetic
      consequences of pulsating and steady flows in combination with several tube
      configurations were evaluated. The results suggested that, by constricting the
      tube and keeping the flow steady, C. subterranea saves on ventilation costs by a
      factor of up to six compared with oscillatory flow in a tube without the tail-fan
      constriction.

PMID- 9639591
TI  - Burrow ventilation in the tube-dwelling shimp Callianassa subterranea (Decapoda:
      thalassinidea). III. Hydrodynamic modelling and the energetics of pleopod
      pumping.
AB  - The process of flow generation with metachronally beating pleopods in a tubiform
      burrow was studied by designing a hydrodynamic model based on a thrust-drag force
      balance. The drag of the tube (including the shrimp) comprises components for
      accelerating the water into the tube entrance, for adjusting a parabolic velocity
      profile, for accelerating the flow into a constriction due to the shrimp's body
      and another constriction due to the extended tail-fan, for shear due to
      separation and for the viscous resistance of all tube parts. The thrust produced
      by the beating pleopods comprises components for the drag-based thrust and for
      the added-mass-based thrust. The beating pleopods are approximated by oscillating
      flat plates with a different area and camber during the power stroke and the
      recovery stroke and with a phase shift between adjacent pleopod pairs. The added
      mass is shed during the second half of the power stroke and is minimized during
      the recovery stroke. A force balance between the pleopod thrust and the tube drag
      is effected by calculating the mean thrust during one beat cycle at a certain
      flow velocity in the tube and comparing it with the drag of the tube at that flow
      velocity. The energetics of the tube and the pump are derived from the forces,
      and the mechanical efficiency of the system is the ratio of these two. Adjusted
      to standard Callianassa subterranea values, the model predicts a mean flow
      velocity in the tube of 1.8 mm s-1. The mean thrust force, equalling the drag, is
      36. 8 microN, the work done by the pleopod pump per beat cycle is 0.91 microJ and
      the energy dissipated by the tube system is 0.066 microJ per cycle. The
      mechanical efficiency is therefore 7.3 %. Pump characteristics that may be varied
      by the shrimp are the beat frequency, the phase shift, the amplitude and the
      difference in pleopod area between the power and recovery strokes. These
      parameters are varied in the model to evaluate their effects. Furthermore, the
      moment of added mass shedding, the distance between adjacent pleopods, the number
      of pleopods and the total tube drag were also varied to evaluate their effects.

PMID- 9639592
TI  - Prolonged swimming, recovery and repeat swimming performance of mature sockeye
      salmon Oncorhynchus nerka exposed to moderate hypoxia and pentachlorophenol.
AB  - Mature, wild sockeye salmon (Oncorhynchus nerka) demonstrated their remarkable
      stamina and recovery abilities by performing three consecutive critical swimming
      speed tests with only a 45 min interval for recovery between subsequent tests.
      Although the repeated swimming challenges were performed without a full recovery,
      normoxic fish swam just as well on the second swim, and the majority of fish swam
      only marginally more poorly on the third swim. In addition, metabolic loading in
      these fish, as measured by the rate of oxygen consumption, ventilation rate and
      plasma lactate levels during recovery, did not appear to be cumulative with
      successive swims. Fish, however, did not recover as well after a similar level of
      initial swimming performance under moderately hypoxic conditions (water PO2>100
      mmHg; 1 mmHg=0.1333 kPa). Four out of the five fish did not swim again and their
      high plasma lactate levels indicated a greater anaerobic effort. In another group
      of fish, metabolic loading (elevated control rates of oxygen consumption) was
      induced with an overnight sublethal exposure to pentachlorophenol, but these fish
      swam as well as normoxic fish on the first swim, and five of the six fish swam
      for a third time at a marginally lower critical swimming speed. In contrast to
      expectations, pentachlorophenol pretreatment and moderate hypoxia were not
      additive in their effects. Instead, the effects resembled those of
      pentachlorophenol pretreatment alone. The results are discussed in terms of what
      aspects of fatigue might impair the repeat swimming performance of sockeye
      salmon.

PMID- 9639593
TI  - Cold inhibition of cell volume regulation during the freezing of insect
      malpighian tubules.
AB  - Cells in freeze-tolerant tissues must survive substantial shrinkage during
      exposure to the hyperosmolarity that results as solutes are excluded from
      extracellular ice. We investigated the possibility that this hyperosmotic shock
      elicits an acute regulatory volume increase (RVI) by monitoring the response of
      epithelial cell volume in the Malpighian tubules of the New Zealand alpine weta
      (Hemideina maori) during exposure to low temperature/hyperosmolarity (mimicking
      freezing conditions) or during an actual freeze/thaw cycle. The cross-sectional
      area of cells in isolated Malpighian tubules was measured using differential
      interference contrast microscopy. At 20 degrees C, cells held in saline
      containing 400 mmol1-1 glucose exhibit an RVI in response to hyperosmotic shock.
      Cross-sectional area decreased by 30% immediately after a change from iso-osmotic
      (0.7 osmol1-1) to hyper-osmotic saline (2.1 osmol1-1, equal to the osmotic shock
      encountered during freezing to -4 degrees C) and then returned to 21% below the
      control value 30 min after the exposure. Although substantial cellular function
      of Malpighian tubules was retained at low temperature (the rate of fluid
      secretion by isolated tubules at 4 degrees C was 72% of that measured at 20
      degrees C), no RVI was observed at 0% degrees C; cross-sectional area was 39%
      below the control value immediately after the hyperosmotic exposure and 36% below
      the control value 30 min after hyperosmotic exposure. Dibutyryl cyclic AMP
      potentiated the RVI observed at 20 degrees C, but failed to elicit an RVI at 0
      degrees C. A substantial RVI was also absent when the saline contained trehalose
      rather than glucose, regardless of whether the tubules were held at 20 degrees C
      or 0 degrees C. The cross-sectional area of cells in saline containing glucose
      remained at approximately 30% below the control value during an entire 30 min
      period of actual freezing to -4 degrees C, suggesting that an acute volume
      regulatory response was in fact inhibited during mild freezing. The inhibition of
      an acute RVI during mild freezing may serve to avoid the energetic expenditure
      associated with volume regulation at a time when the normal defence of cell
      volume appears to be unnecessary.

PMID- 9639594
TI  - Evidence for membrane-bound carbonic anhydrase in the air bladder of bowfin (Amia
      calva), a primitive air-breathing fish.
AB  - The purpose of this study was to examine the subcellular distribution and
      isoenzyme characteristics of carbonic anhydrase from the gills and respiratory
      air bladder of bowfin Amia calva, a primitive air-breathing fish. Separation of
      subcellular fractions by differential centrifugation revealed that the vast
      majority of carbonic anhydrase from the gills of bowfin originated from the
      cytoplasmic fraction. Washing of the gill microsomal pellet also indicated that
      the carbonic anhydrase originally associated with this pellet was largely due to
      contamination from the cytoplasmic fraction. Experiments with a carbonic
      anhydrase inhibitor, sulphanilamide, and the plasma carbonic anhydrase inhibitor
      from this species confirmed that the bowfin gill probably contains only one
      carbonic anhydrase isoenzyme which had properties resembling those of CA II. In
      contrast to the situation in the gills, a relatively large percentage (27%) of
      the total air bladder carbonic anhydrase was associated with the microsomal
      fraction. Washing of the air bladder microsomal pellet removed little of the
      carbonic anhydrase activity, indicating that most of the carbonic anhydrase in
      the microsomal fraction was associated with the membranes. Like the mammalian
      pulmonary CA IV isoenzyme, microsomal carbonic anhydrase from the bowfin air
      bladder was less sensitive to the bowfin plasma carbonic anhydrase inhibitor,
      sodium dodecylsulphate (SDS) and sulphanilamide than was cytoplasmic carbonic
      anhydrase from the air bladder. Microsomal carbonic anhydrase from the bowfin air
      bladder also resembled CA IV in that it appears to be anchored to the membrane
      via a phosphatidylinositol-glycan linkage which could be cleaved by
      phosphatidylinositol-specific phospholipase C. Taken together, these results
      suggest that a membrane-bound carbonic anhydrase isoenzyme resembling mammalian
      CA IV in terms of inhibition characteristics and membrane attachment is present
      in the air-breathing organ of one of the most primitive air-breathing
      vertebrates.

PMID- 9639595
TI  - Visual modulation of olfactory learning in honeybees.
AB  - We use classical conditioning of the honeybee (Apis mellifera) proboscis
      extension reflex with a visual (A) and an olfactory (X) conditioned stimulus in a
      blocking paradigm. Typically, learning about one element (X) of a compound (AX)
      is decreased (blocked) if the other component (A) has previously been rewarded
      alone. Our results show that visual pretraining did not produce blocking in
      honeybees: instead, forward pairings of A with a reward increased subsequent
      learning about X relative to a backward pairing control. This finding violates
      the independence assumption, which holds that elements of inter-modal compound
      stimuli change associative strength independently of each other. Furthermore, it
      is at odds with common theories of conditioning that predict blocking and assume
      that the elements of a compound stimulus rely on one common internal reinforcing
      signal. Taking the functional anatomy of the honeybee brain into account, we
      suggest that vision and olfaction may not rely on the same internal reinforcing
      signal; compound interactions might thus reflect the wiring of the honeybee
      nervous system and the biological significance of different sensory modalities
      during natural behaviour.

PMID- 9639596
TI  - The role of angiotensin in arterial blood pressure regulation in the toad Bufo
      marinus.
AB  - Little is known about the role of the renin-angiotensin system in anuran
      amphibians, although they appear to possess the functional components of such a
      system. We investigated the role of angiotensin (ANG) in arterial blood pressure
      regulation in the conscious toad Bufo marinus using the angiotensin-converting
      enzyme blocker captopril. We found that conversion of endogenous ANG I to ANG II
      made a significant contribution to mean arterial pressure in undisturbed animals.
      The vascular tone contributed by ANG II was not mediated via &agr ; adrenergic
      mechanisms because increases in pressure in response to ANG infusion were
      unaffected by the presence of the &agr ; antagonist phentolamine. Angiotensin
      induced vasoconstriction was shown to be an important mechanism in arterial blood
      pressure regulation in the face of an acute hypotensive perturbation of pressure
      brought about by sodium nitroprusside. Blockade of the conversion of ANG I to ANG
      II significantly delayed the recovery of mean arterial pressure after sodium
      nitroprusside-induced hypotension. This suggests that the renin-angiotensin
      system may play an important role in the initial responses to hypotension in
      anurans, whether brought about by haemorrhage or dehydration.

PMID- 9639597
TI  - Functional citric acid cycle in an arcA mutant of Escherichia coli during growth
      with nitrate under anoxic conditions.
AB  - The operation of the citric acid cycle of Escherichia coli during nitrate
      respiration (anoxic conditions) was studied by measuring end products and enzyme
      activities. Excretion of products other than CO2, such as acetate or ethanol, was
      taken as an indication for a non-functional cycle. From glycerol, approximately
      0.3 mol acetate was produced; the residual portion was completely oxidized,
      indicating the presence of a partially active citric acid cycle. In an arcA
      mutant devoid of the transcriptional regulator ArcA, glycerol was completely
      oxidized with nitrate as an electron acceptor, demonstrating derepression and
      function of the complete pathway. Glucose, on the other hand, was excreted mostly
      as acetate by the wild-type and by the arcA mutant. During growth on glucose, but
      not on glycerol, activities of succinate dehydrogenase and of 2-oxoglutarate
      dehydrogenase were missing nearly completely. Thus, the previously described
      strong repression of the citric acid cycle during nitrate respiration occurs only
      during growth on glucose and is the effect of anaerobic and, more important, of
      glucose repression. In Pseudomonas fluorescens (but not Pseudomonas stutzeri), a
      similar decrease of citric acid cycle function during anaerobic growth with
      nitrate was found, indicating a broad distribution of this regulatory principle.

PMID- 9639598
TI  - Aerobic chemolithoautotrophic growth and RubisCO function in Rhodobacter
      capsulatus and a spontaneous gain of function mutant of Rhodobacter sphaeroides.
AB  - Photosynthetic prokaryotes that assimilate CO2 under anoxic conditions may also
      grow chemolithoautotrophically with O2 as the electron acceptor. Among the
      nonsulfur purple bacteria, two species (Rhodobacter capsulatus and
      Rhodopseudomonas acidophilus), exhibit aerobic chemolithoautotrophic growth with
      hydrogen as the electron donor. Although wild-type strains of Rhodobacter
      sphaeroides grow poorly, if at all, with hydrogen plus oxygen in the dark, we
      report here the isolation of a spontaneous mutant (strain HR-CAC) of Rba.
      sphaeroides strain HR that is fully capable of this mode of growth. Rba.
      sphaeroides and Rba. capsulatus fix CO2 via the reductive pentose phosphate
      pathway and synthesize two forms of ribulose 1, 5-bisphosphate
      carboxylase/oxygenase (RubisCO). RubisCO levels in the aerobic
      chemolithoautotrophic-positive strain of Rba. sphaeroides were similar to those
      in wild-type strains of Rba. sphaeroides and Rba. capsulatus during
      photoheterotrophic and photolithoautotrophic growth. Moreover, RubisCO levels of
      Rba. sphaeroides strain HR-CAC approximated levels obtained in Rba. capsulatus
      when the organisms were grown as aerobic chemolithoautotrophs. Either form I or
      form II RubisCO was able to support aerobic chemolithoautotrophic growth of Rba.
      capsulatus strain SB 1003 and Rba. sphaeroides strain HR-CAC at a variety of CO2
      concentrations, although form II RubisCO began to lose the capacity to support
      aerobic CO2 fixation at high O2 to CO2 ratios. The latter property and other
      facets of the physiology of this system suggest that Rba. sphaeroides and Rba.
      capsulatus strains may be effectively employed for the biological selection of
      RubisCO molecules of altered substrate specificity.

PMID- 9639599
TI  - Cloning and characterization of a Rhizobium meliloti nonspecific acid
      phosphatase.
AB  - Nodulated legumes require high levels of phosphorus for optimal symbiotic
      performance. However, the basis for this elevated phosphorus requirement is
      poorly understood, and very little information regarding bacteroid phosphorus
      metabolism is available. To develop an understanding of the relative importance
      of organic and inorganic phosphorus sources for bacteroids, we investigated
      phosphatase activity in Rhizobium meliloti. An R. meliloti plasmid library clone
      that complemented an Escherichia coli phosphatase mutant was isolated, and the
      clone was sequenced. The complementing fragment contained a 337-amino-acid open
      reading frame that has a potential leader sequence and processing sites
      characteristic of periplasmic proteins. The phosphatase activity was located in
      the periplasm of R. meliloti and of E. coli containing the cloned gene. The
      subunit molecular mass of the cloned phosphatase was 33 kDa, and gel filtration
      indicated the active enzyme was a 66-kDa homodimer. Lack of substrate specificity
      suggests the cloned gene, napD, encodes a nonspecific acid phosphatase with a pH
      optimum of approximately 6.5. An R. meliloti napD transposon-insertion mutant was
      constructed, and its symbiotic phenotype was determined to be Fix+ regardless of
      the level of phosphorus provided to the host plant.

PMID- 9639600
TI  - Carboxin resistance in Paracoccus denitrificans conferred by a mutation in the
      membrane-anchor domain of succinate:quinone reductase.
AB  - Succinate:quinone reductase is a membrane-bound enzyme of the citric acid cycle
      and the respiratory chain. Carboxin is a potent inhibitor of the enzyme of
      certain organisms. The bacterium Paracoccus denitrificans was found to be
      sensitive to carboxin in vivo, and mutants that grow in the presence of 3'-methyl
      carboxin were isolated. Membranes of the mutants showed resistant
      succinate:quinone reductase activity. The mutation conferring carboxin resistance
      was identified in four mutants. They contained the same missense mutation in the
      sdhD gene, which encodes one of two membrane-intrinsic polypeptides of the
      succinate:quinone reductase complex. The mutation causes an Asp to Gly
      replacement at position 89 in the SdhD polypeptide. P. denitrificans strains that
      overproduced wild-type or mutant enzymes were constructed. Enzymic properties of
      the purified enzymes were analyzed. The apparent Km for quinone (DPB) and the
      sensitivity to thenoyltrifluoroacetone was normal for the carboxin-resistant
      enzyme, but the succinate:quinone reductase activity was lower than for the wild
      type enzyme. Mutations conferring carboxin resistance indicate the region on the
      enzyme where the inhibitor binds. A previously reported His to Leu replacement
      close to the [3Fe-4S] cluster in the iron-sulfur protein of Ustilago maydis
      succinate:quinone reductase confers resistance to carboxin and
      thenoyltrifluoroacetone. The Asp to Gly replacement in the P. denitrificans SdhD
      polypeptide, identified in this study to confer resistance to carboxin but not to
      thenoyltrifluoroacetone, is in a predicted cytoplasmic loop connecting two
      transmembrane segments. It is likely that this loop is located in the
      neighborhood of the [3Fe-4S] cluster.

PMID- 9639601
TI  - Two malate dehydrogenases in Methanobacterium thermoautotrophicum.
AB  - Methanobacterium thermoautotrophicum (strain Marburg) was found to contain two
      malate dehydrogenases, which were partially purified and characterized. One was
      specific for NAD+ and catalyzed the dehydrogenation of malate at approximately
      one-third of the rate of oxalacetate reduction, and the other could equally well
      use NAD+ and NADP+ as coenzyme and catalyzed essentially only the reduction of
      oxalacetate. Via the N-terminal amino acid sequences, the encoding genes were
      identified in the genome of M. thermoautotrophicum (strain DeltaH). Comparison of
      the deduced amino acid sequences revealed that the two malate dehydrogenases are
      phylogenetically only distantly related. The NAD+-specific malate dehydrogenase
      showed high sequence similarity to L-malate dehydrogenase from Methanothermus
      fervidus, and the NAD(P)+-using malate dehyrogenase showed high sequence
      similarity to L-lactate dehydrogenase from Thermotoga maritima and L-malate
      dehydrogenase from Bacillus subtilis. A function of the two malate dehydrogenases
      in NADPH:NAD+ transhydrogenation is discussed.

PMID- 9639602
TI  - Identification and characterization of IS1302, a novel insertion element from
      Wolinella succinogenes belonging to the IS3 family.
AB  - A new insertion sequence (IS) designated IS1302 was identified in Wolinella
      succinogenes. IS1302 is 1,306 bp in size with 36-bp imperfect terminal inverted
      repeats. It contains only one open reading frame (tnpA), which encodes a putative
      transposase whose sequence is similar to that of transposases of various IS
      elements of the IS3 family. IS1302 was identified in the genome of a W.
      succinogenes fumarate reductase deletion mutant in which the frd operon had been
      replaced by the kan gene. The insertion of IS1302 occurred when the mutant was
      propagated in the presence of a high concentration of kanamycin. Two different
      target sites of IS1302 were found immediately upstream of the kan gene, where the
      insertion of IS1302 resulted in a duplication of 3 bp of the target DNA. Upon
      insertion of IS1302, new possible promoter structures of the kan gene were
      created, which might lead to a stimulated transcription of the kan gene and
      result in a selective advantage of cells containing IS1302 at one of the two
      target sites. Southern blot analysis suggested the presence of at least 13 copies
      of IS1302 in the genome of W. succinogenes. This is the first IS element
      discovered in W. succinogenes.

PMID- 9639603
TI  - Two membrane anchors of Wolinella succinogenes hydrogenase and their function in
      fumarate and polysulfide respiration.
AB  - Wolinella succinogenes can grow by anaerobic respiration with fumarate or
      polysulfide as the terminal electron acceptor, and H2 or formate as the electron
      donor. A DeltahydABC mutant lacking the hydrogenase structural genes did not grow
      with H2 and either fumarate or polysulfide. In contrast to the wild-type strain,
      the mutant grown with fumarate and with formate instead of H2 did not catalyze
      the reduction of fumarate, polysulfide, dimethylnaphthoquinone, or benzyl
      viologen by H2. Growth and enzymic activities were restored upon integration of a
      plasmid carrying hydABC into the genome of the DeltahydABC mutant. The
      DeltahydABC mutant was complemented with hydABC operons modified by artificial
      stop codons in hydA (StopA) or at the 5'-end of hydC (StopC). The StopC mutant
      lacked HydC, and the hydrophobic C-terminus of HydA was missing in the
      hydrogenase of the StopA mutant. The two mutants catalyzed benzyl viologen
      reduction by H2. The enzyme activity was located in the membrane of the mutants.
      A mutant with both modifications (StopAC) contained the activity in the
      periplasm. The three mutants did not grow with H2 and either fumarate or
      polysulfide, and did not catalyze dimethylnaphthoquinone reduction by H2. We
      conclude that the same hydrogenase serves in the anaerobic respiration with
      fumarate and with polysulfide. HydC and the C-terminus of HydA appear to be
      required for both routes of electron transport and for dimethylnaphthoquinone
      reduction by H2. The hydrogenase is anchored in the membrane by HydC and by the C
      terminus of HydA. The catalytic subunit HydB is oriented towards the periplasmic
      side of the membrane.

PMID- 9639604
TI  - Sulfide oxidation in the phototrophic sulfur bacterium Chromatium vinosum.
AB  - Sulfide oxidation in the phototrophic purple sulfur bacterium Chromatium vinosum
      D (DSMZ 180(T)) was studied by insertional inactivation of the fccAB genes, which
      encode flavocytochrome c, a protein that exhibits sulfide dehydrogenase activity
      in vitro. Flavocytochrome c is located in the periplasmic space as shown by a
      PhoA fusion to the signal peptide of the hemoprotein subunit. The genotype of the
      flavocytochrome-c-deficient Chr. vinosum strain FD1 was verified by Southern
      hybridization and PCR, and the absence of flavocytochrome c in the mutant was
      proven at the protein level. The oxidation of thiosulfate and intracellular
      sulfur by the flavocytochrome-c-deficient mutant was comparable to that of the
      wild-type. Disruption of the fccAB genes did not have any significant effect on
      the sulfide-oxidizing ability of the cells, showing that flavocytochrome c is not
      essential for oxidation of sulfide to intracellular sulfur and indicating the
      presence of a distinct sulfide-oxidizing system. In accordance with these
      results, Chr. vinosum extracts catalyzed electron transfer from sulfide to
      externally added duroquinone, indicating the presence of the enzyme
      sulfide:quinone oxidoreductase (EC 1.8.5.-). Further investigations showed that
      the sulfide:quinone oxidoreductase activity was sensitive to heat and to quinone
      analogue inhibitors. The enzyme is strictly membrane-bound and is constitutively
      expressed. The presence of sulfide:quinone oxidoreductase points to a connection
      of sulfide oxidation to the membrane electron transport system at the level of
      the quinone pool in Chr. vinosum.

PMID- 9639605
TI  - Liver transplantation in children.

PMID- 9639606
TI  - Pediatric liver transplantation: from the full-size liver graft to reduced,
      split, and living related liver transplantation.
AB  - Between 1984 and 1996, the authors performed 499 liver transplants in 416
      children less than 15 years old. The overall patient survival at 10 years was
      76.5%. It was 71.3% for the 209 children grafted in 1984-1990; 78.5% for biliary
      atresia (n = 286), 87.3% for metabolic diseases (n = 59), and 72.7% for acute
      liver failure (n = 22). The 5-year survival was 73.6% for the 209 children
      grafted in 1984-1990 and 85% for the 206 grafted in 1991-1996. Scarcity of size
      matched donors led to the development of innovative techniques: 174 children who
      electively received a reduced liver as a first graft in our center had a 5-year
      survival of 76% while 168 who received a full-size graft had a survival of 85%
      (NS). Results of the European Split Liver Registry showed 6-month graft survival
      similar to results obtained with full-size grafts collected by the European Liver
      Transplant Registry. Extensive use of these techniques allowed the mortality
      while waiting to be reduced from 16.5% in 1984-1990 to 10% in 1991-1992. It rose
      again to 17% in 1993, leading the authors to develop a program of living related
      liver transplantation (LRLT). The legal and ethical aspects are analyzed. Between
      July 1993 and October 1997, the authors performed 53 LRLTs with 90% survival. In
      elective cases, a detailed analysis was made of the 45 children listed for LRLT
      between July 1993 and March 1997 and the 79 registered on the cadaveric waiting
      list during the same period. Mortality while waiting was 2% and 14.5% for the
      LRLT and cadaveric lists, respectively. The retransplantation rate was 4.6% and
      16.1% for LRLT and cadaveric transplants, respectively. Overall post-transplant
      survival was 88% and 82% for children who received a LRLT or a cadaveric graft,
      respectively. Overall survival from the date of registration was 86% and 70% (P <
      0.05) for LRLT or cadaveric LT respectively. The 2-year post-transplant survival
      in children less than 1 year of age at transplantation was 88.8% and 80. 3% with
      a LRLT or cadaveric graft, respectively; patient survival after 3 months post
      transplant was 95.8% and 91.9% for stable children waiting at home, 93.7% and
      93.7% in children hospitalized for complications of their disease, and 89.5% and
      77.7% for children hospitalized in an intensive care unit at the time of
      transplantation for children who received a LRLT or cadaveric graft,
      respectively. It is concluded that LRLT seems to be justified for
      multidisciplinary teams having a large experience with reduced and split liver
      grafting.

PMID- 9639607
TI  - Development of a pediatric liver transplantation program in Argentina.
AB  - This article describes the preliminary experimental steps and clinical
      implementation of a purely pediatric liver transplantation (LT) program in a
      large public children's hospital in Buenos Aires, Argentina, a city with well
      over 10 million inhabitants and a referral population of over 30 million. Between
      1993 and 1997, 84 LTs were performed in 81 patients, of which one-fourth weighed
      below 10 kg. The main indications were biliary atresia (n = 25, 30%) and
      fulminant liver failure (n = 23, 27%), followed by autoimmune cirrhosis (n = 14,
      16%) and other liver diseases. Shortage of organs due to local conditions led to
      the use of liver-reduction techniques in 48 cases (57%), split liver in 2, and
      living-related donor (LRD) in 2. Retransplantation was necessary in 3 instances.
      Seventy-eight percent of the recipients survived for more than 1 year and 71%
      were alive after 4 years. The authors comment on the need for adaptation to local
      conditioning factors when developing a pediatric LT program in any country in
      which demographics and economic, medical, and sociological environments have a
      decisive influence on organ procurement, the actual performance of the operation,
      and the lifelong postoperative medication. In Buenos Aires, where the hospital
      setting is well-developed, the indications are in part determined by the high
      incidence of hepatitis A. Organ shortages in our area led to liberal use of liver
      reduction, split-liver, and LRD techniques. The overall results of the first
      years of such a program were largely satisfactory.

PMID- 9639608
TI  - Changes in growth, growth hormone, and insulin-like growth factor-I (IGF-I) after
      orthotopic liver transplantation.
AB  - Growth failure is an important consequence of chronic liver disease in childhood.
      Insulin-like growth factor-I (IGF-I), which is synthesized and released by the
      liver, plays an important role as a growth regulator in humans. We examined the
      growth hormone (GH)/IGF-I axis before and after orthotopic liver transplantation
      (LT) in 14 children aged between 2 and 11 years (mean 5.6 +/- 1.1 years). Pre
      transplantation serum GH levels (7.5 +/- 1.2 ng/ml) were significantly higher (P
      < 0.001) compared with controls (5 +/- 0.5 ng/ml). However, post-transplantation
      levels (1.8 +/- 0.8 ng/ml) did not differ from those in the control group. Serum
      IGF-I levels showed a statistically significant increase after LT (20.1 +/- 9.4
      vs 190 +/- 66.2 ng/ml; P < 0.001) and became indistinguishable from the levels in
      the control group (180 +/- 96 ng/ml). In comparison with pre-transplantation data
      (z - 2.70), there was an increase in height 4 years postoperatively (z - 1.68).
      Catch-up growth was highly significant, in particular during the 1st year after
      LT (z -1. 58 +/- 1.63 vs 2.59 +/- 5.29; P < 0.01). We conclude that a GH
      resistance state found in patients with severe chronic liver disease reverted
      following LT. Given that IGF-1 depends upon liver function, this could be one of
      the main factors in the significant catch-up growth in pediatric LT recipients.

PMID- 9639609
TI  - Long-term follow-up of patients with biliary atresia successfully treated with
      hepatic portoenterostomy. The importance of sequential treatment.
AB  - The outcome of 18 biliary atresia (BA) patients (5 male, 13 female; age range
      10.7-22.5 years; mean 15.4+/-0.7 years) treated with hepatic portoenterostomy
      (HPE) and jaundice-free for more than 10 years without liver transplantation (LT)
      is analyzed retrospectively. Eight of these patients subsequently required LT
      (age at LT 12. 8+/-0.5 years, range 10.5-15.2 years); 3 children (aged 11.6, 13.2
      and 14.1 years, respectively) had episodes of gastrointestinal variceal bleeding
      associated with other signs of severe disease and are now candidates for LT; and
      among the 7 asymptomatic patients (age range 11.2-22.5 years; mean 15.9+/-2.1
      years), 5 had sonographic and biochemical signs of moderate portal hypertension
      (PH). In order to analyze whether the age at transplantation influences the
      survival of children transplanted for BA, we also reviewed the outcome of 71 BA
      patients transplanted at our hospital between 1986 and 1996. All the children
      older than 10 years at the time of LT were alive; only patients younger than 10
      years died following LT (n = 15). We conclude that the natural outcome of
      extrahepatic BA is toward PH, fibrosis, and cirrhosis, even in those cases
      successfully treated with HPE. In our experience, the results of sequential
      treatment with HPE and LT were excellent.

PMID- 9639610
TI  - Evidence-based operations in paediatric surgery.
AB  - It has been assumed that only 10% of medical interventions are supported by solid
      scientific evidence. The aim of this study was to determine the type of research
      evidence supporting operations in a tertiary referral paediatric surgical unit.
      All patients admitted over a 4-week period to two surgical firms were enrolled in
      the study. All major operations carried out on each patient since birth were
      evaluated. Patients for whom a diagnosis was not reached were excluded. A
      bibliographic database (MEDLINE) was used to search for the articles published
      between January 1986 and December 1995 on the analysed operations. The type of
      evidence supporting the operations was classified as follows: I=evidence from
      randomised controlled trials (RCTs); II=self-evident intervention (obvious
      effectiveness not requiring RCTs); III=evidence from prospective and/or
      comparative studies; IV=evidence from follow-up studies and/or retrospective case
      series; and V=intervention without substantial evidence for or against results of
      randomised trials. Seventy operations (32 individual types) were performed on 49
      patients (1-5 operations/patient); 18 (26%) were supported by RCTs (type of
      evidence I). Two patients (3%) received a self-evident intervention (type II); 48
      operations (68%) were based on non-randomised prospective or retrospective
      studies (type III=13%; type IV=55%). Two patients (3%) received an operation not
      supported by or against convincing scientific evidence (type V). A significant
      proportion of operations in paediatric surgery is supported by RCTs. However, the
      vast majority of these trials were conducted on adult patients. Sixty-eight per
      cent of the operations were based on prospective follow-up studies or
      retrospective case series, which may not represent solid scientific evidence.
      More RCTs are needed in paediatric surgery.

PMID- 9639611
TI  - Oesophageal replacement in the management of corrosive strictures: when is
      surgery indicated?
AB  - The accidental ingestion of corrosive agents is a major cause of oesophageal
      strictures in children. The mainstay of treatment is repeated dilatations.
      Despite this, a significant number of patients eventually require oesophageal
      bypass. We reviewed the records of all cases managed with this condition at the
      University of Cape Town teaching hospitals between 1976 and 1994. Dilatation
      therapy alone was successful in 14 out of 39 patients (41%). Morbidity of failed
      dilatation therapy included repeated hospital admissions over an average 11.5
      months and 17 dilatations each. Oesophageal perforations occurred in 7 cases
      (18%). Early factors predictive of failure of conservative treatment were: delay
      in presentation of more than 1 month; severe pharyngo-oesophageal burns requiring
      a tracheostomy; oesophageal perforation; and a stricture longer than 5 cm on
      radiological assessment. The size of dilators accepted during early bougienage
      also correlated with eventual outcome. These criteria may be useful in predicting
      which patients will not respond to repeated dilatations. Early surgical
      intervention in such cases will prevent fruitless dilatations and related
      complications.

PMID- 9639612
TI  - Longitudinal follow-up of pulmonary function after lobectomy in childhood -
      factors affecting lung growth.
AB  - We examined the changes in pulmonary function values in 27 patients who underwent
      a lobectomy due to cystic lung disease and compared the results regarding such
      factors as disease type, age at operation, and preoperative infections. Percent
      vital capacity (%VC) decreased immediately after lobectomy, but recovered to
      normal values within 2 postoperative years and remained within or above the
      normal range. The ratio of residual volume to total lung capacity (RV/TLC) rose
      temporally with the increase in %VC, but then remained normal after 2
      postoperative years. There was no difference in %VC and RV/TLC between diseases,
      while bronchial atresia showed a significantly lower correlation with percent of
      forced expiratory volume at 1 s. The older group operated upon at over 4 years of
      age and the group that had infections before operation showed relatively low %VC
      and high RV/TLC. Some patients demonstrated extremely low %VC along with funnel
      chest deformities. Our study suggests that overinflation of the remaining lung
      compensates VC in the early period after lobectomy while subsequently alveolar
      multiplication occurs. Factors affecting compensatory lung growth were considered
      to be operation later than 4 years of age, preoperative infection, and a thoracic
      deformity.

PMID- 9639613
TI  - Gastric necrosis in newborns: a report of 11 cases.
AB  - Eleven neonates ranging in gestational age from 34 to 40 weeks presented with
      gastric necrosis. The 4 full-term neonates showed sudden-onset hemorrage and
      "coffee-ground" vomiting; in the 7 premature babies the initial clinical finding
      was abdominal distention. The criteria for diagnosis were: perinatal distress in
      prematures and transient neonatal respiratory distress in full-term babies.
      Radiographic evidence of gastric distention was typical and preceded clinical
      signs of hematemesis and gastric perforation. Surgery was performed in 8
      patients; 3 received medical treatment. At surgery 1 total and 3 subtotal
      gastrectomies and 4 segmental gastric resections were performed. Three of these
      patients died post-operatively as a consequence of multiorgan failure; a second
      look was necessary in one patient 1 week after surgery because of prepyloric
      perforation due to ulcers. Biopsy specimens taken from the site of perforation
      demonstrated extensive necrosis; ulceration was disseminated in the surrounding
      gastric mucosa; no signs of phlogosis were detected. The diagnosis, treatment,
      and physiopathologic considerations are reviewed.

PMID- 9639614
TI  - The influence of laparoscopic surgery on perioperative heat loss in infants.
AB  - Perioperative heat loss is a potentially serious complication of surgery in
      infants. The influence of laparoscopic surgery on perioperative hypothermia has
      not previously been documented. We reviewed heat loss in 26 infants undergoing
      laparoscopic pyloromyotomies compared with 42 control patients having the
      standard open procedure over the same time period. The mean fall in temperature
      in the laparoscopic group was -0.69 degreesC compared with -0.47 degreesC in the
      open group. This difference was not significant, with a P value of 0.077. This
      may reflect the small sample size and the relatively short duration of this
      procedure with few instrument changes. There was a trend for increased heat loss
      in the laparoscopic group, which might have implications for longer and more
      complex laparoscopic procedures in infants.

PMID- 9639615
TI  - The use of laparoscopy in the diagnosis and treatment of abdominal complications
      of ventriculo-peritoneal shunts in children.
AB  - Ventriculo-peritoneal shunts (VPS) are the most frequent operative procedures
      used to treat hydrocephalic children. Abdominal complications of VPS are now a
      rare event; however, their frequency varies from 5% to 47% according to reports.
      Anything that causes an obstruction or impediment of the VP derivation system
      will lead to intracranial hypertension, which requires immediate surgery. From
      1985 to 1995 at the Division of Pediatric Surgery of the Federico II University
      of Naples, ten laparoscopies were performed in ten children with VPS
      complications. Cerebrospinal fluid pseudocysts were found in four infants. There
      was one case of abdominal wall perforation by the tip of the catheter at the
      umbilical level, two bowel obstructions, and one catheter was lost in the
      abdominal cavity. Finally, two children had malfunctioning of the peritoneal limb
      of the catheter. The laparoscopic technique was curative in all ten cases, thus
      avoiding a conventional laparotomy and the consequent risk of adhesions, which
      could cause further complications.

PMID- 9639616
TI  - Multidisciplinary evaluation of the distended abdomen in critically ill infants
      and children: the role of bedside sonography.
AB  - Abdominal distention and metabolic acidosis are common in critically ill infants
      and children, and can be manifestations of an intra-abdominal catastrophe. This
      series demonstrates the value of bedside sonography (US) in this difficult
      assessment. Eight infants and children presented with the above situation. Seven
      were immediately post-cardiopulmonary resuscitation and none had antecedent
      histories of abdominal pain or bilious vomiting. Abdominal radiographs could not
      rule out intra-abdominal pathology such as ischemic bowel. Review of all
      laboratory and radiological data showed US to be a discerning modality for acute
      bowel pathology. A characteristic pattern of echogenic ascites, thickened bowel
      wall, dilated, fluid-filled bowel lumen, and lack of peristalsis was seen in
      those children with gangrenous bowel. Sonographic examination accurately
      predicted the status of the bowel in all patients. Four patients survived: two
      had segmental ileal necrosis, one had localized gangrene of the jejunum (twice),
      and one had necrotic bowel from a closed-loop obstruction. The four who died had
      malrotation with volvulus (two), superior mesenteric venous thrombosis, and one
      was immunocompromised with pulmonary aspiration. We conclude that bedside US can
      be extremely valuable as an adjunct in assessing the abdomen and diagnosing
      gangrenous bowel in critically ill infants and children.

PMID- 9639617
TI  - Reliability of color Doppler and power Doppler sonography in the evaluation of
      intussuscepted bowel viability.
AB  - In two similar cases of irreducible intussusception with wall necrosis and
      perforation, symptoms had begun 24 h before admission and the plain radiographs
      showed signs of small-bowel obstruction. The sonographic (US) appearances,
      however, were different: color Doppler (CD) US showed vascular flow in the
      intussuscepted bowel in one case and no flow in the other. After radio-clinical
      assessment, both children underwent surgery and an intestinal resection had to be
      performed, manual reduction being impossible. The reliability of the US findings
      and the prognostic value of CD and power Doppler US in determining the viability
      of the intussuscepted bowel are discussed with a review of the literature.

PMID- 9639618
TI  - Intestinal volvulus and right-sided blunt trauma: consequence or coincidence?
AB  - Two boys developed bile-stained vomiting shortly after being involved in
      significant right-sided blunt trauma and sustaining fractured right femurs. Both
      had intestinal volvulus and both had a history of bile-stained vomiting in
      infancy, which had been investigated and interpreted as normal.

PMID- 9639619
TI  - Meconium ileus secondary to cystic fibrosis. The East London experience.
AB  - Meconium ileus (MI) affects 15% of neonates with cystic fibrosis (CF). The
      authors reviewed the management and outcome of 51 neonates presenting to a single
      institution between 1976 and 1995 with MI secondary to CF. Clinical presentation
      included abdominal distension (96%), bilious vomiting (49%), and delayed passage
      of meconium (36%). A family history of CF was present in 4 cases (8%). Twenty
      three neonates presented with MI and evidence of volvulus, atresia, or
      perforation (complicated MI). Of these, 16 underwent stoma formation, 1
      appendicectomy, and 6 resection with primary anastomosis. Twenty-eight neonates
      presented with uncomplicated MI. Of these, 11 were managed non-operatively by
      Gastrografin enema (10) or enteral N-acetylcysteine (1). The remainder required
      stoma formation (15) or bowel resection with primary anastomosis (2). Early
      postoperative complications occurred in 2 neonates (4%). In this hospital the 1
      year survival for this condition has increased from 49% (1953-1970) to 98% (1976
      1995) irrespective of the surgical procedure performed or the presence of
      volvulus, atresia, or perforation. In our experience, bowel resection with
      primary anastomosis is as safe as stoma formation and is associated with a
      reduced length of initial hospital stay.

PMID- 9639620
TI  - The Malone antegrade colonic enema procedure: outcome and lessons of 6 years'
      experience.
AB  - The successful management of faecal incontinence can dramatically improve the
      quality of life of affected children. The introduction of the non-refluxing,
      catheterisable appendico-caecostomy provides the opportunity to treat previously
      resistant patients. Over a 6-year period, 29 children had a Malone antegrade
      continent stoma for enema administration (MACE). Incontinence was related to
      spina bifida in 12 children, ano-rectal anomaly in 12, Hirschprung's disease in
      2, followed excision of a pelvic tumour in 2, and was secondary to intractable
      chronic constipation in 1. The conduit was fashioned from the appendix (20), a
      caecal tube (8), or a gastric tube (1). Surgical complications were stomal
      stenosis (11), wound infection (1), anastomotic leak (1), MACE stoma prolapse
      (1), and a pressure sore (1). Colonic irrigation was achieved with washouts of
      saline (24), saline plus phosphate (4), and saline plus Picolax (1). Twenty-three
      patients have complete control of bowel function, but 4 still soil. Two remain
      incontinent, 1 of whom is still being instructed. One child subsequently had a
      colostomy, but still uses the MACE stoma. Successful bowel management requires
      motivation, dedication, commitment, and the input of a clinical nurse specialist.
      The MACE is a relatively straightforward operative procedure that provides an
      effective washout technique that is acceptable to both parents and children.

PMID- 9639621
TI  - Duplication of the rectum: report of four cases and review of the literature.
AB  - Rectal duplications are rare anomalies. Recently, we observed four cases of
      rectal duplication, each presenting with different clinical features including
      chronic constipation, a prolapsing rectal "polyp, " a "growth" from the vulva,
      and acute retention of urine. The variety of clinical presentations may lead to
      delay in diagnosis and multiple operations.

PMID- 9639622
TI  - Parenting children with anorectal malformations: implications and experiences.
AB  - Parents play a crucial role in the life of a child suffering from an anorectal
      malformation (ARM), since their guidance contributes to the degree to which the
      child learns to cope with his or her disability. We investigated whether they
      experience stress in parenting such a child and also attempted to identify
      somatic or behavioral characteristics in the child that influence the stress of
      parenting. The parents of 109 children (69 males, 40 females; median age 5.9
      years, range 1-18 years) with an ARM (58 low, 10 intermediate, 41 high) were
      studied. The Nijmegen Questionnaire on Child-rearing Situations (NQCS) was used
      to investigate the existing parenting situation. Behavioral characteristics of
      the children were studied by means of the Child Behaviour Checklist (CBCL) and
      the Teacher Report Form (TRF). In a semi-structured interview, we investigated
      how parents experienced the implications of the disability in everyday life with
      their child. Our study showed that as far as the perception of parenting stress
      is concerned, parents of children with an ARM do not differ from those with
      healthy primary-school children. Within the group of parents with ARM-afflicted
      children, the parents of older, incontinent children experienced relatively more
      stress, especially when the child concerned was male. With regard to the
      children's behavior, the parents and teachers under investigation did not report
      a higher than normal incidence of deviant behavior. However, when individual
      parents observed difficult behavior in their child, they found it harder to deal
      with than the incontinence for feces. Regarding the implications of the disorder
      for their everyday lives, parents were concerned and indicated a need for
      specific counselling. We conclude that having a child with a somatic affliction,
      in this case an ARM, does not automatically imply that the parents experience
      child-rearing problems. However, certain groups of parents are more at risk,
      i.e., parents with older, incontinent sons and parents with children exhibiting
      behavioral problems. In addition, our study shows that parents do have
      difficulties in coping with the implications of the disorder and express a need
      for support. We feel that patient care can be improved if aid is tailored to
      these specific problems.

PMID- 9639623
TI  - Torsion of the adnexa in children: the value of laparoscopy.
AB  - Experience with adnexal torsion in neonates and children is often disappointing.
      Delay between the first symptoms and operation is important, and adnexal loss the
      rule. The authors reviewed their experience and the literature to assess the
      appropriate diagnostic and therapeutic approach. Diagnostic procedures (standard
      ultrasonography [US], color Doppler US, computed tomography, magnetic resonance
      imaging, endorectal US, and diagnostic laparoscopy) are discussed; for neonates
      and premenarcheal girls a specific surgical approach is proposed. Twenty-seven
      adnexal torsions treated between 1985 and 1995 in the same institution were
      retrospectively reviewed. Neonatal (7) and premenarcheal cases (20) were
      separated. The neonatal cases (7) were all operated upon: 4 adnexectomies, 2
      oophorectomies, and 1 detorsion with cystectomy were performed. In the
      premenarcheal group (20) 8 adnexectomies, 6 oophorectomies, 5 detorsions with
      cystectomy, and 1 salpingectomy were performed. There were only 6 salvaged adnexa
      in this series. In the neonatal group, US seemed accurate in predicting
      complicated cases. Prenatal puncture of large (>40 mm) ovarian cysts is possible.
      The authors advocate a laparoscopic approach in the first days of life of all
      uncomplicated cysts independent of size in order to increase the percentage
      salvaged. In ultrasonic complicated cases a delayed operation is proposed in the
      premenarcheal group, endorectal US will probably become the diagnostic method of
      choice for complicated ovaries; other methods were disappointing. In order to
      increase adnexal salvage, the authors recommend a laparoscopic approach in the
      emergency situation if a clinical examination is positive as well as better
      medical (pediatricians, gynecologists) and general (girls, parents) information.
      They suggest controlateral oophoropexy in cases of torsion of a normal adnexum.

PMID- 9639624
TI  - Effect of cyclosporine on fertility in male rats.
AB  - The effect of cyclosporine (CsA) on fertility has assumed greater importance with
      the increasing numbers of pediatric transplantations being performed all over the
      world. Conflicting reports on the effects of CsA on sex hormones are available.
      This experimental animal study was designed to examine the effect of CsA on
      testicular weight, sperm counts, seminiferous tubular diameter (STD), testicular
      morphology, DNA flowcytometry, sex hormone levels, and fertility in male rats.
      Those rats who received CsA (20 mg/kg per day) showed significant reductions in
      testicular weight (P < 0.05), sperm count (P < 0.01), Johnsen score (P < 0.05),
      STD (P < 0.01), serum testosterone levels (P < 0.05), haploid cell population (P
      < 0. 001) in the testis, and fertility (P < 0.001) compared to those receiving
      CsA 10 mg/kg per day and control rats. These findings will have an important
      bearing for children receiving cyclosporine for long periods to guide the
      physician in optimally adjusting long-term treatment.

PMID- 9639625
TI  - Fertility and unilateral undescended testis in the rat model II.
AB  - Continuing experimental work on the effect of experimentally created unilateral
      undescended testis (UL-UDT) in neonatal rats, this study examined the fertility
      and correlated it to contralateral (CL) testicular morphology, seminiferous
      tubular diameter (STD), DNA flowcytometry, and the presence of serum anti-sperm
      antibodies (ASA) at 120-135 days of age. In our previous reported work, the
      fertility of rats with UL-UDT at 65-80 days of age was the same as that of
      controls. In the present study the rats with UL-UDT had significantly reduced
      fertility (P < 0.01) compared to controls, even though the Johnsen scores and
      mean STD of the CL testicular tissue were comparable. DNA flowcytometry
      demonstrated a significant decrease (P < 0.001) in haploid cell population in the
      CL testicular tissue of rats with UL-UDT. Furthermore, the rats with UL-UDT who
      either received an immunosuppressive or in whom the UDT was excised early showed
      almost normal fertility and DNA histograms like those of controls. Significantly
      high titres of serum ASA were detected only in the group with UL-UDT when tested
      at 135 days of age. From these results, in combination with earlier results on
      similar work, it may be inferred that UL-UDT causes immunologically-mediated,
      progressive damage to the CL descended testis, leading to a decrease in fertility
      in rats.

PMID- 9639626
TI  - Upper-tract changes after treatment of posterior urethral valves.
AB  - This paper discusses the long-term sequelae in the upper urinary tract with
      respect to hydroureteronephrosis (HUN), vesicoureteral reflux (VUR), renal
      parenchymal disease, and their correlation with renal function in 84 boys with
      posterior urethral valves followed for 1 to 21 years. Thirty-one boys (39.3%)
      were adolescents or older at the time of review. The incidence of high-grade VUR
      (grade III or more) was 47.6% at presentation, and resolution following
      decompression of the lower urinary tract occurred in 38.7% of refluxing units.
      VUR was associated with a high incidence of chronic renal failure (CRF) (30%) on
      long-term follow up; however, 16% of non-refluxing patients also progressed to
      CRF. The incidences of renal parenchymal disease and persistent upper-tract
      dilatation in the non-refluxing group were 25% and 50% of renal units
      respectively. Gross HUN persisted in 12.3% of patients despite decompression and
      reconstructive surgery, with vesicoureteral junction (VUJ) obstruction being
      documented in 1 patient only. Moderate and mild upper-tract dilatation persisted
      in 31.6% and 43.9% of patients, respectively. Persistent gross HUN was associated
      with a very high incidence of CRF (92.3%), while 88.4% of those with persistent
      mild/moderate dilatation maintained normal renal function over a follow-up period
      ranging from 1 to 21 years. This study emphasizes the need for systematic
      evaluation to exclude VUJ obstruction and abnormal urodynamics as a cause of
      persistent HUN so that effective therapy can be instituted early to relieve back
      pressure and to provide a low-pressure reservoir with effective emptying. In the
      absence of either of these causes, persistent ureterectasis after treatment is
      presumably due to secondary peristaltic failure as a consequence of ureteral
      fibrosis, ureteral tortuosity, or developmental dysplasia.

PMID- 9639627
TI  - The evolution of biofilms in venous access devices implanted in children with
      Wilms' tumour.
AB  - Biofilms form on all implanted foreign materials. In venous access ports (VAPs),
      the biofilm with entrapped organisms may be the source of recurring bacteraemia.
      At present, little is known of the development of biofilms in VAPs. In this study
      light, scanning, and transmission electron microscopy were used to investigate
      the evolution of biofilms in VAPs implanted in 15 African children with Wilms'
      tumour. The VAPs were removed either emergently because of infection (n = 6) or
      blockage (n = 3), or electively at the end of chemotherapy (n = 6). Intact
      biofilms were obtained from lengths of the catheter attached to ports that had
      been in place for 11 days to 3 years. Each was prepared for light and electron
      microscopy. In infected ports, shortly after implantation biofilms were thin and
      comprised of apparently healthy erythrocytes (RBCs) and occasional platelets,
      leucocytes (WBCs), and bacteria enmeshed in a network of fibrin. Three weeks
      after implantation, RBCs had autolysed and large numbers of WBCs and bacterial
      colonies were present within and on the luminal surface. In 1 instance, the lumen
      of a VAP had been occluded by a "plug" of WBCs. In non-infected patients, the
      biofilms in long-standing VAPs were of varying thickness and primarily composed
      of an amorphous granular material. In most cases, healthy and necrotic bacteria
      were present both within the core and on the surface of the biofilms. The results
      suggest that while bacteria, per se, are an important factor, the presence and
      degradation of blood components may be an equally important factor in the
      development of biofilms in VAP catheters.

PMID- 9639628
TI  - An outbreak of post-surgical wound infections due to Mycobacterium abscessus.
AB  - An outbreak of post-operative wound infections due to Mycobacterium abscessus is
      described. During a 5-month period 45 post-surgical patients developed wound
      infection, manifested by wound breakdown, cellulitis, and discharge and
      progressing slowly to suppuration and sinus formation. The majority (43/45) had
      undergone out-patient operations, and 40 had had surgery in the inguinal region.
      The source of infection was identified as contaminated tap water. A study
      revealed serious deficiencies in the disinfection and sterilisation techniques
      employed in the operating theatre (OT), including major defects in the
      autoclaving machine. The outbreak was controlled after several specific measures
      were instituted. The patients responded well to treatment with conventional first
      line anti-tuberculous drugs administered for 3-8 months. The report highlights
      the necessity of strict monitoring of disinfection and sterilisation techniques
      in surgical units and OTs.

PMID- 9639629
TI  - To tube or not to tube: do infants and children need post-laparotomy gastric
      decompression?
AB  - The purpose of this study was to evaluate the role of nasogastric (NG)
      decompression after laparotomy in pediatric surgical practice: 94 children who
      underwent abdominal surgery by a single surgeon were consecutively prospectively
      managed without postoperative NG tubes. Patients with either bowel obstruction or
      intra-abdominal infection were excluded from the study. These children were
      compared with 94 retrospective, matched controls who were routinely managed with
      postoperative NG decompression by the same surgeon. Data were analyzed with
      regard to patient, operative, and outcome variables. There was no difference in
      gender, age (3.8 +/- 0.5 vs 3.5 +/- 0.4 years, P > 0.7), or postoperative
      complications (P > 0.8) between the two groups. However, there was a higher
      incidence of postoperative vomiting (22% vs 11%, P > 0.05) in the children who
      did not have postoperative NG decompression. Nevertheless, a significant decrease
      in time to first feed, first stool, and discharge was noted in the group of
      patients managed without NG tubes (P < 0.05). NG decompression thus need not be
      routinely used in the pediatric patient undergoing abdominal surgery, as there is
      no difference in postoperative complications and the hospital stay is shortened.

PMID- 9639630
TI  - Esophageal hiatal hernia after omphalocele repair.
AB  - Esophageal hiatal hernias (EHH) are probably caused by congenital, traumatic, or
      iatrogenic factors, although the etiology remains unknown. EHHs may develop after
      abdominal wall closure for omphalocele or gastroschisis due to the increased
      intra-abdominal pressure, however, there have been few reports in the literature.
      We present a case of EHH developing after abdominal wall closure.

PMID- 9639631
TI  - Congenital microgastria: a case report and review of literature.
AB  - Congenital microgastria is an uncommon result of impairment of normal foregut
      development. To date, only 39 cases have been described in the literature. We
      report a boy born with microgastria and bilateral hypoplastic kidneys who had
      feeding problems, resulting in failure to thrive and growth retardation. After a
      short period of conservative management, he was operated upon at the age of 11
      months. A Hunt-Lawrence pouch was created, leading to toleration of increasing
      amounts of oral feeding. Although his feeding problems have decreased, his height
      and weight are below normal (<10th percentile). The embryology, clinical
      presentation, diagnostic procedures, associated anomalies, and management are
      discussed.

PMID- 9639632
TI  - Rapid enlargement of a choledochal cyst: antenatal diagnosis and delayed primary
      excision.
AB  - A case of choledochal cyst (CC) antenatally diagnosed at 29 weeks' gestation is
      reported. Rapid enlargement of the cyst soon after delivery resulted in complete
      gastric outlet obstruction (GOO). The lesion was treated by external drainage as
      a temporary maneuver, with delayed cyst excision and hepaticoduodenostomy at the
      hepatic hilum performed at 81 days of age. Surgical treatment of CC in early
      infancy has been reported to be safe and effective. However, delayed primary
      excision would be an alternative procedure, especially in rare cases showing
      rapid enlargement resulting in GOO, since this choice has the potential advantage
      of allowing weight gain and improved nutritional status without risking interim
      complications due to the drainage procedure.

PMID- 9639633
TI  - Colonic atresia secondary to a choledochal cyst.
AB  - Colonic atresia and choledochal cyst are both uncommon congenital abnormalities.
      We report a case in which the two conditions coexisted and propose an
      aetiological link.

PMID- 9639634
TI  - Spiral computed tomography for bilioenteric anastomotic stricture.
AB  - Spiral computed tomography scanning after intravenous cholangiography (IVC-SCT)
      was used to assess the anatomy of the biliary tree and anastomosis in a 7-year
      old girl with recurrent cholangitis 5 years after surgical excision of a
      choledochal cyst. The technique clearly visualized the stenosis of the
      hepaticojejunostomy and hepatic duct and the dilated intrahepatic ducts. IVC-SCT
      provides a precise, prompt, and accurate image with minimal invasiveness and is
      especially suitable for the preoperative evaluation of pediatric patients.

PMID- 9639635
TI  - Splenic torsion in the presence of renal agenesis.
AB  - A 14-year-old male with left renal agenesis presented with a history of
      intermittent abdominal pain for over 1 year. At laparotomy, the cause was found
      to be splenic torsion. The case is presented with a literature review. A theory
      of the cause is also presented based on the regional anatomy and embryology.

PMID- 9639636
TI  - Cystic degeneration of heterotopic pancreas.
AB  - The case of a large cyst arising from heterotopically-situated pancreatic tissue
      in an 11-month-old girl is reported. This is the first published report of
      childhood pancreatic cyst that developed in heterotopic pancreatic tissue. There
      is strong evidence to suggest that the cyst became symptomatic as a result of
      secondary infection, an additional unreported phenomenon. This case serves to
      underscore the fact that pancreatic cysts should be considered in the
      differential diagnosis of intestinal duplication cysts of childhood.

PMID- 9639638
TI  - Large, septated ileal duplication cyst in a 4-year old, simulating the urinary
      bladder.
AB  - A 4-year-old boy presented with acute abdominal pain and a 1-year history of
      intermittent umbilical complaints. Ultrasonographic examination demonstrated a
      large cyst in the lower abdomen divided by a thin membrane. With micturition,
      impaired bladder function was expected. Initial suprapubic drainage produced
      1,000 ml dark-brown liquid. Laparotomy revealed an ileal duplication cyst.
      Preoperative computed tomography and laparoscopy with the cyst drained did not
      further clarify the diagnosis.

PMID- 9639637
TI  - Intraluminal hamartoma of the ileum in a child: a rare cause of intestinal
      occlusion.
AB  - A case of small-intestinal obstruction in a 12-year-old boy caused by an
      intraluminal hamartoma of the ileum is reported. The rarity of the lesion, its
      location, symptomatology, histology, and diagnosis are discussed.

PMID- 9639639
TI  - An unusual domestic accident: a penetrating abdominal wound with intestinal
      evisceration in a child.
AB  - We report a penetrating abdominal injury due to a piece of glass, a very unusual
      domestic accident, in a 2-year-old boy who was admitted to the emergency
      department with an evisceration through the umbilicus. His mother reported that
      she was asleep when the boy came to her room, and did not know how it had
      happened. We primarily suspected child abuse, but the presence of a piece of
      glass in the boy's heel led us to think of a domestic accident. He had poured
      himself a glass of water, and then fell on the glass. We could not find a similar
      case in the literature on domestic accidents.

PMID- 9639640
TI  - Currarino's triad: an unusual cause of constipation in children.
AB  - A 6-year-old girl presented with intractable constipation. On investigation, she
      was found to have an association of anorectal stenosis, anterior sacral defect,
      and anterior meningocoele (Currarino's triad). The meningocoele was excised and a
      Duhamel pull-through procedure performed after resection of a massively distended
      rectosigmoid. Post-operatively, she started having spontaneous bowel action.
      Early diagnosis and management is recommended to avoid the high mortality and
      morbidity associated with this condition.

PMID- 9639641
TI  - Neonatal scrotal faecal fistula.
AB  - Incarceration of a congenital inguinal hernia, if untreated promptly, can result
      in dreaded complications like faecal fistula. We report one neonate who presented
      with a scrotal faecal fistula due to late presentation.

PMID- 9639642
TI  - Cystic lymphangioma of the scrotum.
AB  - A 7-year-old boy who presented with a painful left hemiscrotal mass was diagnosed
      with acquired lymphangioma of the scrotum. Chronic friction from a cast for
      Perthes' disease might have been the cause of sudden enlargement of a congenital
      lymphangioma of the scrotum. Magnetic resonance imaging (MRI) was useful for
      preoperative diagnosis and determining the extent of the scrotal lesions. Total
      excision of the mass leaving the overlying skin was successfully performed. The
      clinical significance of MRI for preoperative diagnosis and planning surgical
      resection of this lesion is discussed.

PMID- 9639643
TI  - Gonadal preservation in a simple testicular cyst.
AB  - The authors report a case of a simple testicular cyst in a 16-week-old infant.
      Preoperative ultrasonography helped to diagnose this condition accurately.
      Gonadal preservation and enucleation of testicular cysts are possible with a
      careful surgical approach, and orchiectomy is not necessary.

PMID- 9639644
TI  - Infantile myofibromatosis: a rare presentation with intussusception.
AB  - Infantile myofibromatosis (IM) is a distinct but rare clinicopathological entity
      occurring in neonates and infants. It probably represents a rare soft-tissue
      tumour made up of undifferentiated myofibroblasts. Its recognition is important
      since it can be mistaken for a malignancy when, in fact, it has a generally
      benign prognosis with spontaneous regression. We describe the first case of an
      infant with IM presenting with acute intussusception due to gastrointestinal as
      well as the typical skin involvement.

PMID- 9639645
TI  - Median nerve compression in Proteus syndrome.
AB  - Proteus syndrome is a multi-organ disorder, a prime feature of which is localized
      gigantism, usually clinically obvious. Symptoms secondary to hypertrophy of
      nerves has not been previously recognized as a part of the syndrome.

PMID- 9639646
TI  - Experience with a new technique of primary gastrostomy button placement in
      association with the Nissen fundoplication.
AB  - The tube gastrostomy has always been associated with significant morbidity,
      mainly because of difficulty in immobilisation, resultant dislodgement, and
      problems with replacement. Between January and October 1994, we employed a method
      of primary button gastrostomy in 18 patients with excellent results.
      Complications have been minimal. There has been no incidence of intra-peritoneal
      gastric leakage, wound infection, or button dislodgement. Two patients have had
      peristomal ulceration.

PMID- 9639647
TI  - Open gastrostomy performed through the umbilicus.
AB  - A new variation of open gastrostomy placement is described in which a Stamm
      gastrostomy is performed via a supraumbilical incision around the circumference
      of the umbilicus. Access to the stomach is good and the cosmetic result is
      superior to that obtained with the conventional incision.

PMID- 9639648
TI  - Deflating proximal enterostomy for jejunoileal atresia.
AB  - A modification is described to avoid postoperative gaseous distension and
      facilitate early oral feeding after resection and anastomosis for jejunoileal
      atresia.

PMID- 9639649
TI  - Venous access via the renal vein: a technical innovation.
AB  - A patient with difficult venous access is described in whom both haemodialysis
      and parenteral nutrition were required. To minimize the impact on transplant
      prospects, the renal veins were used for vascular access. The technique and
      rationale for this novel approach are presented.

PMID- 9639650
TI  - Scroto-peritoneal port for laparoscopic orchidopexy.
AB  - Recently, laparoscopic orchidopexy has been accepted as the standard procedure of
      management for clinically impalpable testes. However, many techniques have been
      described for the delivery of the mobilized testes. In this report, a new
      approach is described. The use of a fourth "scroto-peritoneal" port, makes
      complete laparoscopic orchidopexy possible, and in addition, is safe and easy to
      perform.

PMID- 9639651
TI  - Hepatobiliary cystadenoma with hyaline stroma.

PMID- 9639652
TI  - Dictyostelium discoideum Hsp32 is a resident nucleolar heat-shock protein.
AB  - Hsp32 is a small shock protein in Dictyostelium discoideum that is expressed in
      growing cells in the absence of heat shock. Here we show that Hsp32 is an Ag-NOR
      staining protein capable of binding DNA with high affinity. Hsp32 is also shown
      to be a resident nucleolar protein both under normal growth conditions and during
      heat stress. In unstressed cells, Hsp32 localizes to the nucleolar periphery in a
      pattern reminiscent of the rDNA in this organism. During the first several hours
      of heat shock, the peripheral localization of Hsp32 is not altered, although rDNA
      transcription is arrested. Prolonged heat shock causes a condensation of the
      rDNA. Under these conditions, Hsp32 is no longer predominantly associated with
      the rDNA, but is instead distributed over the entire nucleolus. Hsp32 therefore
      retains ist nucleolar localization under prolonged heat shock conditions by
      associating with nucleolar components other than the rDNA or rRNA.

PMID- 9639653
TI  - Remodeling of chromatin loops does not account for specification of replication
      origins during Xenopus development.
AB  - We have investigated the possible relationship between replicons and chromatin
      loops during Xenopus development. In early embryos, replication of the ribosomal
      RNA genes (rDNA) can initiate at apparently any sequence. Nevertheless, the need
      for a regular spacing of replication origins suggests that some periodic
      chromatin folding might dictate which sites are actually used for initiation.
      After the midblastula transition, replication initiation is restricted to the
      rDNA intergenic spacers. A remodeling of chromatin folding could account for this
      change in origin usage. Here, it is reported that nuclear matrix anchorage of the
      Xenopus rDNA occurs at multiple, apparently random sequences, throughout
      embryonic development as well as in adult cells. In vitro matrix rebinding assays
      confirmed the lack of specific anchoring sequences in the rDNA, before as well as
      after specific replication origins are established. Thus, no change in loop
      attachment sites could explain the change in origin usage at this locus.
      Nonspecific loop anchorage was a special feature of the rDNA locus, since the
      same nuclear matrices were able selectively to bind the scaffold attachment
      region (SAR) of the Drosophila histone gene cluster in vitro. Blastula and
      gastrula nuclear matrices bound a higher amount of SAR sequences than matrices
      from later stages or adult cells. This developmental change in SAR binding might
      explain the increase in size of the bulk of genomic DNA loops that occurs after
      the gastrula stage. However, no change in chromatin loop organization that could
      explain the midblastula stage transition from small to large replicons was
      observed.

PMID- 9639654
TI  - Centromeric genotyping and direct analysis of nondisjunction in humans: Down
      syndrome.
AB  - In species with chiasmate meioses, alterations in genetic recombination are an
      important correlate of nondisjunction. In general, these alterations fall into
      one of two categories: either homologous chromosomes fail to pair and/or
      recombine at meiosis I, or they are united by chiasmata that are suboptimally
      positioned. Recent studies of human nondisjunction suggest that these
      relationships apply to our species as well. However, methodological limitations
      in human genetic mapping have made it difficult to determine whether the
      important determinant(s) in human nondisjunction is absent recombination, altered
      recombination, or both. In the present report, we describe somatic cell hybrid
      studies of chromosome 21 nondisjunction aimed at overcoming this limitation. By
      using hybrids to "capture" individual chromosomes 21 of the proband and parent of
      origin of trisomy, it is possible to identify complementary recombinant meiotic
      products, and thereby to uncover crossovers that cannot be detected by
      conventional mapping methods. In the present report, we summarize studies of 23
      cases. Our results indicate that recombination in proximal 21q is infrequent in
      trisomy-generating meioses and that, in a proportion of the meioses,
      recombination does not occur anywhere on 21q. Thus, our observations indicate
      that failure to recombine is responsible for a proportion of trisomy 21 cases.

PMID- 9639655
TI  - Ordered arrangement and rearrangement of chromosomes during spermatogenesis in
      two species of planarians (Plathelminthes).
AB  - The pattern of distribution of telomeric DNA (TTAGGG), 28S rDNA, and 5S rDNA has
      been studied using fluorescence in situ hybridization (FISH) and primed in situ
      labelling during spermatogenesis and sperm formation in the filiform spermatozoa
      of two species of planarians, Dendrocoelum lacteum and Polycelis tenuis
      (Turbellaria, Plathelminthes). In both species, the positions of FISH signals
      found with each probe sequence are constant from cell to cell in the nuclei of
      mature sperm. Chromosome regions containing 5S and 28S rDNA genes are gathered in
      distinct bundles of spiral form. In early spermatids with roundish nuclei, the
      sites of a given sequence on different chromosomes remain separate. Centromeres
      (marked by 5S rDNA) gather into a single cluster in the central region of the
      slightly elongated sperm nucleus. During spermatid maturation, this cluster
      migrates to the distal pole of the nucleus. In Polycelis, telomeric sites gather
      into three distinct clusters at both ends and in the middle of the moderately
      elongated nucleus. These clusters retain their relative positions as the
      spermatid matures. All the chromosome ends bearing 28S rDNA gather only into the
      proximal cluster. Our data suggest that structures in the nucleus selectively
      recognise chromosome regions containing specific DNA sequences, which helps these
      regions to find their regular places in the mature sperm nucleus and causes
      clustering of the sites of these sequences located on different chromosomes. This
      hypothesis is supported by observations on elongated sperm of other animals in
      which a correlation exists between ordered arrangement of chromosomes in the
      mature sperm nucleus and clustering of sites of the same sequence from different
      chromosomes during spermiogenesis.

PMID- 9639656
TI  - Unordered arrangement of chromosomes in the nuclei of chicken spermatozoa.
AB  - The arrangement of chromosomes in the elongated sperm nuclei of chicken was
      studied using fluorescence in situ hybridization with probes specific for
      telomeres of all chromosomes, a microchromosome, the long arm of chromosome 6,
      the large heterochromatic block on the Z-chromosome, and the same heterochromatic
      block plus subtelomeric sites on macrochromosomes 1-4. The positions of all
      probes vary from one sperm to another. No order in chromosome arrangement is
      apparent. It is suggested that large chromosome size and small chromosome number
      correlate with constant positions of chromosomes and vice versa. Based on the
      known quantity of repetitive units of the repeat on the Z-chromosome, the degree
      of compaction of chromatin in the chicken sperm nucleus is estimated as ca 0.7
      Mb/ microm. As judged from the length of the heterochromatic region of the Z
      chromosome at the lampbrush stage, the total length of the Z-chromosome in mature
      sperm is 2.5-4 times that of the sperm nucleus.

PMID- 9639658
TI  - Improved detection and comparative sizing of human chromosomal telomeres in situ.
AB  - Telomeric length dynamics are thought to play an important role both in the
      processes of cellular aging and cancer progression. We have revised the primed in
      situ (PRINS) labeling technique to allow an estimation of the relative length of
      individual telomeres. We illustrate the applicability of the approach by
      demonstrating different telomeric sizes not only between blood lymphocytes from a
      young and an old donor, but also among bone marrow cells from hematological
      cancer patients. In the latter case we found general variations in telomeric
      sizes as well as individual telomeric variations that would have escaped
      detection by other methods. An interesting finding was the selective expansion of
      a single telomere within a specific subset of cells.

PMID- 9639657
TI  - CENP-G: a new centromeric protein that is associated with the alpha-1 satellite
      DNA subfamily.
AB  - A new constitutive centromere-specific protein (CENP) has been identified as a
      result of its recognition as an autoantigen by serum from a patient with gastric
      antral vascular ectasia disease. Conventional immunoblotting and two-dimensional
      double blotting with both this antiserum and a known anti-centromere antiserum
      showed that this antiserum predominantly recognized a Mr 95,000 protein that is
      different from all known CENPs. We have named this new protein CENP-G. This
      protein was detected at the centromeric region throughout the cell cycle. In
      mitosis, it was restricted to the kinetochore inner plate as shown by immunogold
      labeling and electron microscopy. The centromeres of some human chromosomes are
      known to contain two subfamilies of alpha-satellite DNA. Using immunofluorescence
      combined with fluorescent in situ hybridization with subfamily-specific DNA
      probes, we revealed that CENP-G was specifically associated with one of the
      subfamilies, which we have named alpha-1, but not the other. The localization and
      the alpha-1-specific association suggested that CENP-G may play a role in
      kinetochore organization and function. Like CENP-B and C, but unlike CENP-A, this
      protein remained with the nuclear matrix after intensive extraction. While CENP-B
      is absent from the human Y chromosome, the existence of CENP-G on the Y
      chromosome has been proven by immunofluorescence and whole chromosome painting.
      CENP-G was also detected in CHO, Indian muntjac and Chinese muntjac cells,
      suggesting that it is conserved in evolution.

PMID- 9639659
TI  - Sex chromosome linkage of chicken and duck type I interferon genes: further
      evidence of evolutionary conservation of the Z chromosome in birds.
AB  - Type I interferons (IFNs) are a family of proteins that are predominantly
      expressed in response to viral infection. Two serologically distinct forms of
      type I IFN, designated ChIFN1 and ChIFN2, have recently been recognized in the
      chicken. ChIFN1 is encoded by a cluster of ten or more intronless genes, whereas
      ChIFN2, whose primary sequence is 57% identical, is encoded by a single
      intronless gene. By fluorescence in situ hybridization we now demonstrate that
      the genes for ChIFN1 and ChIFN2 are all located on the short arm of the chicken Z
      chromosome. This assignment was confirmed by results that showed that DNA from
      male (ZZ) chickens yielded approximately twofold stronger Southern blot signals
      with ChIFN1 and ChIFN2 hybridization probes than DNA from females (ZW). Attempts
      to determine differences in IFN production between male and female chickens
      failed owing to a high degree of variation in virus-induced IFN expression
      between individuals of both sexes. Sex linkage of IFN genes was also observed in
      domestic ducks: fluorescence in situ hybridization of duck metaphase chromosomes
      with a duck type I IFN probe was confined to the terminal region of the long arm
      of the Z chromosome. Thus, in contrast to mammals, which have their IFN genes on
      autosomes, birds have the type I IFN genes on the sex chromosome.

PMID- 9639660
TI  - Two separate conserved domains of eukaryotic DNA topoisomerase I bind to each
      other and reconstitute enzymatic activity.
AB  - The two-hybrid system was used to identify proteins that interact with the
      central conserved domain of Saccharomyces cerevisiae DNA topoisomerase I. Several
      different C-terminal domain-containing fragments of topoisomerase I, none of
      which overlapped with the central domain, were identified as specific interacting
      polypeptides. Coexpression of these two domains in yeast partially complemented
      the growth defects of top1-top2ts and top1-hpr1 mutants. Moreover, an in vitro
      assay showed that some topoisomerase I enzymatic activity was restored to these
      mutants. The results demonstrate that the central domain of topoisomerase I
      interacts with the C-terminal domain of the protein and that these two domains
      reconstitute enzymatic activity in vivo, even when expressed as separate
      polypeptides.

PMID- 9639661
TI  - Growth promotion by homocysteine but not by homocysteic acid: a role for
      excessive growth in homocystinuria or proliferation in hyperhomocysteinemia?
AB  - Excessive growth of long bones in patients with homocystinuria is still
      unexplained and previous work incriminating homocysteic acid could not be
      confirmed by others. In vitro studies from our laboratory showed that
      homocysteine stimulated growth in a clonogenic assay. This observation made us
      study plasma cyclin dependent kinase (CDK), homocyst(e)ine and homocysteic acid
      in 10 patients with homocystinuria and 20 controls. In addition, homocysteine and
      homocysteic acid were tested in a clonogenic assay to correlate the growth
      promoting activity with CDK. Plasma CDK (protein) correlated strongly with
      homocysteine (r=0.84) but not with homocysteic acid. Supernatants of the
      clonogenic assay samples showed up to three times higher CDK levels in the
      presence of homocyst(e)ine but not homocysteic acid. In vitro data and the strong
      correlation between homocysteine and CDK suggest a role for homocysteine
      stimulating CDK, the starter of mitosis, with subsequent stimulation of growth.

PMID- 9639662
TI  - Increased transcription decreases the spontaneous mutation rate at the thymidine
      kinase locus in human cells.
AB  - Transcription increases DNA repair efficiency and modulates the distribution of
      certain types of DNA damage. Furthermore, increased transcription level
      stimulates spontaneous mutation rate in yeast. We explored whether transcription
      level affects spontaneous mutation rate in human cells. We first developed two
      thymidine kinase (tk) inducible human cell lines using the Gal4-Estrogen receptor
      system. In our TK6i-G3 and G9 tk heterozygous cell lines, the active tk allele is
      linked to an inducible promoter element. Tk mRNA is induced following treatment
      with estrogen. Spontaneous mutation rate was significantly decreased in human
      cell lines after induction in contrast to the report in yeast. Thus, humans may
      have evolved different or additional mechanisms to deal with transcription
      related spontaneous mutagenesis.

PMID- 9639663
TI  - The role of neuronal growth factors in neurodegenerative disorders of the human
      brain.
AB  - Recent evidence suggests that neurotrophic factors that promote the survival or
      differentiation of developing neurons may also protect mature neurons from
      neuronal atrophy in the degenerating human brain. Furthermore, it has been
      proposed that the pathogenesis of human neurodegenerative disorders may be due to
      an alteration in neurotrophic factor and/or trk receptor levels. The use of
      neurotrophic factors as therapeutic agents is a novel approach aimed at restoring
      and maintaining neuronal function in the central nervous system (CNS). Research
      is currently being undertaken to determine potential mechanisms to deliver
      neurotrophic factors to selectively vulnerable regions of the CNS. However, while
      there is widespread interest in the use of neurotrophic factors to prevent and/or
      reduce the neuronal cell loss and atrophy observed in neurodegenerative
      disorders, little research has been performed examining the expression and
      functional role of these factors in the normal and diseased human brain. This
      review will discuss recent studies and examine the role members of the nerve
      growth factor family (NGF, BDNF and NT-3) and trk receptors as well as additional
      growth factors (GDNF, TGF-alpha and IGF-I) may play in neurodegenerative
      disorders of the human brain.

PMID- 9639664
TI  - Phospholipase D activity is altered in X-linked adrenoleukodystrophy heterozygous
      carriers, but not in hemizygous patients.
AB  - Abnormalities in levels of choline and its metabolites have been reported in the
      lesions of brains of X-linked adrenoleukodystrophy (X-ALD) patients. We have
      examined the turnover of the major choline-containing phospholipid,
      phosphatidylcholine (PtdCho), in fibroblasts from hemizygous X-ALD, heterozygous
      X-ALD, Zellweger syndrome (ZW), and male and female control individuals to assess
      possible alterations in PtdCho metabolism mediated by activation of protein
      kinase C (PKC). Hydrolysis of PtdCho by phospholipase D (PLD) and resynthesis of
      PtdCho from labeled choline were stimulated 2- to 4-fold by PKC activation with
      the phorbol ester, 4beta-12-O-tetradecanoylphorbol-13-acetate (beta-TPA), in all
      cells except those from heterozygous X-ALD individuals. No differences in
      quantity or intracellular distribution of PKC activity, PKC isoforms by Western
      blot analysis, or of the PKC substrate, myristoylated alanine-rich C kinase
      substrate (MARCKS), were apparent in any of the cells. Thus, altered PtdCho
      metabolism was not directly linked to either of these inherited defects that
      result in abnormal peroxisomal functions. Further, altered responsiveness of PLD
      in X-ALD heterozygotes was independent of changes in PKC and MARCKS.

PMID- 9639665
TI  - Utilization of microhomologous recombination in yeast to generate targeting
      constructs for mammalian genes.
AB  - We have developed a new procedure utilizing microhomologous recombination in
      yeast to generate targeting constructs for producing targeted mutations in mice.
      This procedure is rapid and efficient, and should be directly applicable to all
      mammalian genes. Moreover, only minimal information about the locus being
      targeted is required. The feasibility of this approach was demonstrated by
      producing another allele of the mouse Tg737 polycystic kidney gene.

PMID- 9639666
TI  - Role of intracellular second messengers and reactive oxygen species in the
      pathophysiology of V. cholera O139 treated rabbit ileum.
AB  - Vibrio cholerae O139 has pandemic potential and it produces copious amounts of
      fluid secretion. The levels of various second messengers (intracellular Ca2+,
      cAMP, IP3, PKC) were measured to determine the cause of fluid secretion produced
      by this strain of V. cholerae. There was a significant increase in the levels of
      these second messengers in V. cholerae O139 treated ileum as compared to control
      ileum (enterocytes). Levels of these second messengers were also assessed in V.
      cholerae 569B induced fluid secretion in rabbit ileum and it was found that the
      levels were raised more in V. cholerae O139 treated ileum than in V. cholerae
      569B treated rabbit ileum. The intestinal damage was assessed by measuring
      changes in the extent of lipid peroxidation of the enterocytes. Intracellular
      second messengers are known to raise the extent of lipid peroxidation. In V.
      cholerae O139 treated loops calcium ionophore A23187 enhanced the extent of lipid
      peroxidation whereas l-verapamil could only marginally decrease the lipid
      peroxidation. Dantrolene and H7 significantly decreased the extent of lipid
      peroxidation of enterocytes in V. cholerae O139 treated rabbit ileum. However,
      PMA could not enhance further the extent of lipid peroxidation in V. cholerae
      O139 treated rabbit ileum. So intracellular calcium and protein kinase C appear
      to be involved in intestinal damage caused by V. cholerae O139. Reactive oxygen
      species are responsible for causing tissue damage and the extent of oxidative
      damage depends on the balance between the pro-oxidants and the anti-oxidants. So
      the changes in the enterocytes' antioxidant level during V. cholerae O139
      mediated intestinal infection was estimated. There was a significant decrease in
      the enterocyte level of the antioxidant enzymes SOD, catalase, glutathione
      peroxidase, glutathione reductase, glutathione transferase and glucose-6
      phosphate dehydrogenase in V. cholerae O139 mediated intestinal infection. So a
      significant decrease in the levels of antioxidant defenses and a significant
      increase in the levels of second messengers appear to be important in mediating
      V. cholerae O139 induced lipid peroxidation which contributes to the changes in
      membrane permeability and thus to fluid secretion.

PMID- 9639667
TI  - Caffeine does not potentiate gamma-radiation induced DNA damage in ataxia
      telangiectasia lymphoblastoid cells.
AB  - Ataxia telangiectasia (AT) cells display a profound sensitivity to ionizing
      radiation, exhibiting more frequent chromosomal breaks, increased micronuclei
      formation and abnormal DNA repair kinetics following exposure. Despite the recent
      cloning of the ATM gene there remains a need for a simple and rapid means of
      discriminating AT heterozygotes from normal individuals. Caffeine (1,3,7
      trimethyl xanthine), known to inhibit the repair of double-strand DNA breaks
      following ionizing radiation, increases the frequency of radiation induced
      chromosomal breaks in normal cells. Here we report that caffeine potentiates the
      induction of chromosomal breaks in G2 arrested AT heterozygote and normal
      lymphoblastoid cells, but not in homozygous AT lymphoblastoid cells. This
      observation parallels the findings reported by others that caffeine fails to
      potentiate the effect of ionizing radiation in radiation-sensitive yeast strains
      and radiation sensitive CHO cells. It also suggests that caffeine may somehow
      mimic the effect of the ATM gene product in normal cells. We also report that
      caffeine is unlikely to be useful in helping to discriminate AT heterozygotes
      from normal individuals.

PMID- 9639668
TI  - Antimicrobial peptides derived from pepsinogens in the stomach of the bullfrog,
      Rana catesbeiana.
AB  - Three antimicrobial peptides, which had strong antimicrobial activity against a
      broad spectrum of microorganisms, were isolated from the stomach of the bullfrog,
      Rana catesbeiana. Two of the antimicrobial peptides were found to be derived from
      the N-terminal sequences of pepsinogen A and C prosequences. The amino acid
      sequences of the new antimicrobial peptides, named bullfrog pepsinogen A-derived
      antimicrobial peptide (bPaAP) and bullfrog pepsinogen C-derived antimicrobial
      peptide (bPcAP), were Gly-Val-Val-Lys-Val-Ser-Arg-Leu-Lys-Gly-Glu-Ser-Leu-Arg-Ala
      Arg-Leu (MW 1865.5) and Ile-Ile-Lys-Val-Pro-Leu-Lys-Lys-Phe-Lys-Ser-Met-Arg-Glu
      Val-Met-Arg-A sp-His-Gly-Ile-Lys-Ala-Pro-Val-Val-Asp-Pro-Ala-Thr-Lys-Tyr (MW
      3691.6), respectively. The bPaAP and bPcAP adopted 35% and 42% amphipathic alpha
      helical structure in 50% trifluoroethanol, respectively, and were non-hemolytic
      up to a concentration of 200 microg/ml. Synthesized pepsinogen C prosequences of
      monkey and human, which had similar structural characteristics as bPaAP and
      bPcAP, also showed antimicrobial activity at concentrations of 10-200 microg/ml.
      The third peptide was buforin I, previously found in the stomach of the Asian
      toad, Bufo bufo gargarizans. These findings strongly suggest that peptides
      derived from the prosequences of pepsinogens, along with buforin I, may
      contribute to the antimicrobial function of the gastrointestinal mucosa of
      vertebrates, including human.

PMID- 9639669
TI  - A method to score micronuclei in vivo using cytochalasin B-induced cytokinesis
      block.
AB  - The present paper describes an in vivo micronucleus assay using Cytochalasin B
      (CyB). Mice bearing three different tumours, fibrosarcoma (Swiss albino mice),
      B16 F1 melanoma (C57 BL) and Ehrlich ascites carcinoma (Swiss albino mice), were
      injected with repeated doses of CyB at different time intervals and binucleate
      cells were scored at 24, 36, 48, 60 and 72 h after CyB injection. It was found
      that three doses of 3+2+2 mg/kg CyB administered intraperitoneally (i.p.) at 12-h
      intervals effectively blocked cytokinesis. The maximum number of binucleated
      cells (BNC) was scored at 60 h after the last CyB dose. This dose schedule was
      also effective in scoring micronuclei in BNC after irradiation.

PMID- 9639671
TI  - The functions of the preplate in development and evolution of the neocortex and
      hippocampus.
AB  - Recently, it has been shown that the early developmental organization of the
      archicortical hippocampus resembles that of the neocortex. In both cortices at
      embryonic stages, a preplate is present, which is split by the formation of the
      cortical plate into a marginal zone and a subplate layer. The pioneer neurons of
      the preplate are believed to form a phylogenetically ancient cortical structure.
      Neurons in these preplate layers are the first postmitotic neurons and have
      important roles in the development of the cerebral cortex. Cajal-Retzius cells in
      the marginal zone regulate the phenotype of radial glial cells and may direct
      neuronal migration establishing the inside-out gradient of corticogenesis.
      Furthermore, pioneer neurons form the initial axonal connections with other
      (sub)cortical structures. A significant difference between the hippocampus and
      neocortex, however, is that in the hippocampus, most afferents are guided by the
      pioneer neurons in the prominent marginal zone, while in the neocortex most
      ingrowing afferent axons enter via the subplate. At later developmental periods,
      most pioneer neurons disappear by cell death or transform into other neuronal
      shapes. Here, we review the early developmental organization of the mammalian
      cerebral cortex (both neocortex and hippocampus) and discuss the functions and
      fate of pioneer neurons in cortical development, in particular that of Cajal
      Retzius cells. Evaluating the developmental properties of the hippocampus and
      neocortex, we present the hypothesis that the distribution of the main ingrowing
      afferent systems in the developing neocortex, which differs from the one in the
      hippocampal region, may have enabled the specific evolution of the neocortex.

PMID- 9639670
TI  - Fewer chromosome aberrations and earlier apoptosis induced by DNA synthesis
      inhibitors, a topoisomerase II inhibitor or alkylating agents in human cells with
      normal compared with mutant p53.
AB  - The human lymphoblastoid cell lines TK6 (normal p53) and WI-L2-NS or WTK1 (mutant
      p53) differ in sensitivity to killing and induction of gene mutations and
      chromosome aberrations by ionizing radiation. This may be related to decreased
      apoptosis in the cells with mutated p53, such that more damaged cells survive. We
      compared the response of the two cell types to various chemicals. First, to
      ensure that the thymidine kinase deficiency does not increase the sensitivity of
      TK6 tk+/- cells to mutagens, we demonstrated that they were not hypersensitive to
      aberration induction by altered DNA precursor pools or DNA synthesis inhibition,
      by aphidicolin (APC), methotrexate, hydroxyurea (HU), cytosine arabinoside and
      thymidine. TK6 cells were then compared with WI-L2-NS or WTK1 cells. With APC,
      HU, methyl methanesulfonate (MMS), ethyl nitrosourea (ENU) and etoposide (etop),
      TK6 cells had more apoptosis in the first two days after treatment. Fewer
      aberrations were seen in normal p53 TK6 cells than the mutant p53 WI-L2-NS cells,
      ranging from very little difference between the two cell types with MMS to very
      large differences with ENU and etop. For MMS and ENU we followed cultures for
      several days, and found that WI-L2-NS cells underwent delayed apoptosis 3 to 5
      days after treatment, in parallel with published observations with ionizing
      radiation. WI-L2-NS cells also had a delayed increase in aberrations (up to 5
      days post-treatment) when no aberrations remained in TK6 cells. Colony forming
      efficiency was measured for APC, MMS and ENU, and was greater in the p53 mutant
      cells. Our results show that normal p53 function is required for rapid and
      efficient apoptosis in these lymphoblastoid cells with DNA synthesis inhibitors,
      alkylating agents and a topoisomerase II inhibitor, and support the hypothesis
      that induced levels of aberrations are higher in p53 mutant cells because of a
      failure to remove damaged cells by apoptosis.

PMID- 9639672
TI  - Coding defect and a TATA box mutation at the bilirubin UDP
      glucuronosyltransferase gene cause Crigler-Najjar type I disease.
AB  - Mutations at the bilirubin UDP-glucuronosyltransferase (transferase) gene in a
      severely hyperbilirubinemic Crigler-Najjar (CN) type I individual was compared
      with that in a moderately hyperbilirubinemic CN II individual. The CN-I (CF)
      patient in this study sustained a TATA box insertional mutation which was paired
      with a coding defect at the second allele, unlike all coding defects previously
      seen in CN-I patients. The sequence of the mutant TATA box, [A(TA)8A], also seen
      in the CN-II patient, was compared with that at the wild-type box, [A(TA)7A].
      Transcriptional activity with [A(TA)8A] was 10-15% that with the wild-type box
      when present in the -1.7 kb upstream regulatory region (URR) of the bilirubin
      transferase UGT1A1 gene which was fused to the chloramphenicol acetyl transferase
      reporter gene, pCAT 1.7H, and transfected into HepG2 cells. Also, a construct
      with a TA deletion, [A(TA)6A], was prepared and used as a control;
      transcriptional activity was 65% normal. The coding region defect, R336W, seen in
      CF (CN-I) was placed in the bilirubin transferase UGT1A1 [HUG-Br1] cDNA, and its
      corresponding protein was designated UGT1A1*32. The UGT1A1*32 protein supported 0
      10% normal bilirubin glucuronidation when expressed in COS-1 cells. The I294T
      coding defect seen at the second allele in SM (CN-II) generated the UGT1A1*33
      mutant protein which supported 40-55% normal activity with a normal Km (2.5
      microM) for bilirubin. The hyperbilirubinemia seen in SM decreased in response to
      phenobarbital treatment, unlike that seen in CF. Parents of the patients were
      carriers of the respective mutations uncovered in the offspring. The TATA box
      mutation paired with a deleterious missense mutation is, therefore, completely
      repressive in the CN-I patient, and is responsible for a lethal
      genotype/phenotype; but when homozygous, i.e. paired with itself, as previously
      reported in the literature, it is far less repressive and generates the mild
      Gilbert's phenotype.

PMID- 9639673
TI  - The form of iron oxide deposits in thalassemic tissues varies between different
      groups of patients: a comparison between Thai beta-thalassemia/hemoglobin E
      patients and Australian beta-thalassemia patients.
AB  - Mossbauer spectra of 12 beta-thalassemia/hemoglobin E spleen samples from Thai
      patients who had not received multiple blood transfusions and chelation therapy
      and seven beta-thalassemia spleen samples from Australian patients who had
      received multiple blood transfusions and chelation therapy were recorded with
      sample temperatures of 78 K. Each spectrum was found to consist of a
      superposition of a relatively intense central doublet characteristic of high-spin
      Fe(III), a low intensity sextet of peaks due to magnetic hyperfine-field
      splitting, and occasionally a doublet that could be attributed to heme iron. A
      significant (P=0.01) difference (Kolmogorov-Smirnov statistic of 0.71) between
      the distributions of sextet signal intensity as a fraction (Fs) of the total non
      heme iron Mossbauer spectral signal for the two groups of patients was detected.
      The distribution of Fs for the Thai beta-thalassemia/hemoglobin E spleens had a
      mean value of 0.128 (S.D. 0.035) while that for the Australian beta-thalassemia
      spleens had a mean of 0.27 (S.D. 0.12). No significant difference between the
      distributions of non-heme iron concentrations in the tissues for the two groups
      of patients was detected by atomic absorption spectrometry. This study shows that
      the Australian beta-thalassemia patients had a higher fraction of their non-heme
      spleen iron in a goethite-like form than the Thai beta-thalassemia/Hb E patients.

PMID- 9639674
TI  - DNA damage and cytotoxicity induced by beta-lapachone: relation to poly(ADP
      ribose) polymerase inhibition.
AB  - beta-Lapachone (3,4-dihydro-2,2-dimethyl-2H-naphtho[1,2-b]pyran-5, 6-dione) was
      previously shown to enhance the lethality of X-rays and radiomimetic agents and
      its radiosensitizing role in mammalian cells was attributed to a possible
      interference with topoisomerase I activity. Furthermore, beta-lapachone alone was
      found to induce chromosomal damage in Chinese hamster ovary (CHO) cells. The aim
      of the present study was to further elucidate the possible mechanisms by which
      beta-lapachone exerts its genotoxic action in cultured mammalian cells. Flow
      cytometry analysis of beta-lapachone-treated CHO cells indicated a selective
      cytotoxic effect upon S phase of the cell cycle. beta-lapachone produced DNA
      strand breaks as determined by alkaline elution assay; alkaline elution profiles
      from treated cells showed a bimodal dose-response pattern, with a threshold dose
      above which a massive dose-independent DNA degradation was observed. Furthermore,
      beta-lapachone increased the capacity of crude CHO cellular extracts to unwind
      supercoiled plasmid DNA, while significantly inhibiting in vitro poly(ADP-ribose)
      polymerase (PARP). These results suggest that damage induction is probably
      mediated by the interaction between beta-lapachone and cellular enzymatic
      function(s), rather than reflecting a direct action on the DNA. We suggest that
      the inhibition of PARP plays a central role in the complex biological effects
      induced by beta-lapachone in CHO cells.

PMID- 9639675
TI  - Neuroleptic drug-stimulated iron uptake by synaptosome preparations of rat
      cerebral cortex.
AB  - Neuroleptic-induced tardive dyskinesia has been linked to impaired iron
      homeostasis in the central nervous system attributed to increased iron levels. A
      chlorpromazine stimulatory effect upon iron uptake from 55Fe-citrate and 55Fe
      transferrin by cortical synaptosome preparations of rats was recently
      demonstrated. The present work extends this study to other neuroleptic drugs such
      as thioridazine, haloperidol, clozapine and fluphenazine. Like chlorpromazine,
      thioridazine showed a stimulatory effect upon iron uptake from both iron donors
      whereas fluphenazine highly increased uptake from 55Fe-citrate but not from 55Fe
      transferrin. Haloperidol and clozapine had no effect. Stimulation of iron uptake
      by neuroleptics is probably related to their property of calmodulin antagonism,
      since calmidazolium also stimulated synaptosomal iron uptake from both donors.
      Calmidazolium-stimulated uptake from 55Fe-citrate was approx. 5-fold when
      compared to control samples while uptake from 55Fe-transferrin was 250% higher.
      The results are in agreement with the iron uptake magnitude observed with the
      different drugs for the two iron donors used and the reported Ki values of
      neuroleptic drugs for calmodulin antagonism evaluated by the inhibition of 3',5'
      monophosphate phosphodiesterase activity. Moreover, vanadate, an inhibitor of
      protein phosphorylation and KCl-promoted membrane depolarization, greatly
      inhibited iron uptake from 55Fe-citrate by both chlorpromazine-treated and
      untreated synaptosome preparations.

PMID- 9639676
TI  - Chromosome abnormalities in peripheral blood lymphocytes from Cebus apella
      (Cebidae, Platyrrhini) after X-ray irradiation.
AB  - In this paper, we describe the results of a qualitative and quantitative study of
      chromosomal reorganizations observed in X-irradiated (1Gy and 2Gy) and cultured
      lymphocytes from Cebus apella. A total of 646 breakpoints have been detected,
      identified and localized in the ideogram of the species. The breakpoint
      distribution along chromosomes, p and q arms, and bands is not random.
      Chromosomes #11, #12 and chromosome arms 1p, 12p, 13p, 15p, 11q, and 12q are
      significantly more affected than expected, while chromosome #19 and chromosome
      arm 19q are less affected. Terminal regions of chromosome arms accumulate a
      higher number of breakpoints than the rest of the chromosome (37.82%). A high
      percentage (93.66%) of breakpoints is found in G negative bands.

PMID- 9639677
TI  - Pattern generation for stick insect walking movements--multisensory control of a
      locomotor program.

PMID- 9639678
TI  - Presenilin-1 mutations associated with familial Alzheimer's disease do not
      disrupt protein transport from the endoplasmic reticulum to the Golgi apparatus.
AB  - Mutations in genes encoding presenilin-1 (PS1) and presenilin-2 (PS2) have been
      linked to familial forms of Alzheimer's disease (AD). Cells expressing mutant
      presenilins produce elevated levels of Abeta42, the major amyloid peptide found
      in AD plaques. The mechanism whereby this occurs remains unknown, but the
      localization of presenilins to endoplasmic reticulum (ER) and Golgi compartments
      has suggested that they may function in intracellular trafficking pathways
      involved in processing beta-amyloid precursor proteins (APP). To test this
      possibility, we coexpressed PS1(wt), PS1(M146L), or PS1(L286V) in HEK293 cells
      together with the LDL receptor, a classic glycoprotein marker that undergoes post
      translational O-glycosylation in the Golgi compartment. Pulse-chase analysis of
      the receptor indicated that mutant presenilins had no effect on ER-->Golgi
      transport. Similar results were obtained when the studies were carried out with
      cells expressing the Swedish variant of APP (SWAPP751) instead of the LDL
      receptor. Moreover, secretion of the soluble exodomain polypeptide fragments of
      SWAPP751 that arise from alpha-secretase and beta-secretase cleavage was not
      markedly affected by the PS1 mutants. Despite the lack of discernible effect of
      the PS1 mutants on trafficking of proteins through the Golgi apparatus, they
      caused a substantial increase in the proportion of Abeta42 relative to total
      Abeta in the culture medium. The results suggest that mutant forms of PS1 cause
      elevated production of Abeta42 by a mechanism that is independent of a major
      disruption of exocytic trafficking of APP.

PMID- 9639679
TI  - DNA damage caused by common cytological fixatives.
AB  - Tissues from nine species of plants and fungi were treated separately with eight
      solutions, including seven cytological fixatives (3.7% formaldehyde at pH 3.0 and
      7.0, FAA at pH 3.0 and 7. 0, 1% glutaraldehyde at pH 3.0 and 7.0, and Lavdowsky's
      fluid at pH 3.0) and one storage buffer (SED=NaCl-EDTA-DMSO, pH 7.0). DNA from
      untreated tissue and SED-treated tissue was of high molecular weight (>50 kb).
      DNA from glutaraldehyde-treated tissues averaged 20 kb in length, while DNA from
      all other treatments averaged less than 8 kb in length. Each DNA was subjected to
      amplification using the polymerase chain reaction, followed by sequencing of 250
      bp near the 3' end of the nuclear rRNA small subunit gene. Glutaraldehyde
      treatments (at pH 3.0 and 7.0) produced damaged bases at rates of 0. 0% to less
      than 0.1%. Treatments with Lavdowsky's fluid (containing mercuric chloride), FAA
      at pH 7.0, and SED produced rates of 0.0% to 3.6%. FAA at pH 3.0 produced rates
      of 7.6% to 15.6%. Nearly 100 attempts to amplify from specimens treated with 3.7%
      formaldehyde (at pH 3.0 and 7.0) failed, indicating extreme damage to the DNA.

PMID- 9639680
TI  - Estrogen-induced tumorigenesis in the pituitary gland of TGF-beta(+/-) knockout
      mice.
AB  - Transforming growth factor (TGF)-beta receptor type II gene (Tgfbr2) knockout and
      wild type mice underwent chronic estrogen exposure using estradiol pellets.
      Histological examination of the pituitary glands found 38 adenomas in 14
      Tgfbr2(+/-) mice but only one tumor in ten wild type mice. Pituitary
      tumorigenesis is greatly accelerated in Tgfbr2(+/-) mice by estrogen treatment.

PMID- 9639681
TI  - Assembly of a high-resolution map of the Acadian Usher syndrome region and
      localization of the nuclear EF-hand acidic gene.
AB  - Usher syndrome type 1C (USH1C) occurs in a small population of Acadian
      descendants from southwestern Louisiana. Linkage and linkage disequilibrium
      analyses localize USH1C to chromosome 11p between markers D11S1397 and D11S1888,
      an interval of less than 680 kb. Here, we refine the USH1C linkage to a region
      less than 400 kb, between genetic markers D11S1397 and D11S1890. Using 17 genetic
      markers from this interval, we have isolated a contiguous set of 60 bacterial
      artificial chromosomes (BACs) that span the USH1C critical region. Exon trapping
      of BAC clones from this region resulted in the recovery of an exon of the nuclear
      EF-hand acidic (NEFA) gene. However, DNA sequence analysis of the NEFA cDNA from
      lymphocytes of affected individuals provided no evidence of mutation, making
      structural mutations in the NEFA protein unlikely as the cellular cause of
      Acadian Usher syndrome.

PMID- 9639682
TI  - Similar mutational spectra in the HPRT gene of human and hamster cell lines after
      exposure to either low dose rate or high dose rate X-rays.
AB  - The dose rate at which cells are exposed to X-rays may influence the nature of
      induced mutations. To investigate this, the molecular spectra were determined at
      the HPRT gene in a hamster (V79) and a human (WI-L2-NS) cell line after the same
      total dose of X-rays has been administered at either a low dose rate (LDR; 3.33
      mGy/min) or a high dose rate (HDR; 1.24-1.4 Gy/min) X-irradiation. Mutational
      spectra appeared similar, the fraction of mutants carrying deletions ranging
      between 59%-66% for the V79 strain and between 64%-75% for the WI-L2-NS strain,
      and independent of the irradiation conditions. The data indicate no effect of
      ongoing repair processes under LDR conditions on the kind of induced mutations in
      mammalian cells.

PMID- 9639683
TI  - Human chondroitin 6-sulfotransferase: cloning, gene structure, and chromosomal
      localization.
AB  - Chondroitin 6-sulfotransferase (C6ST) is the key enzyme in the biosynthesis of
      chondroitin 6-sulfate, a glycosaminoglycan implicated in chondrogenesis,
      neoplasia, atherosclerosis, and other processes. C6ST catalyzes the transfer of
      sulfate from 3'-phosphoadenosine 5'-phosphosulfate to carbon 6 of the N
      acetylgalactosamine residues of chondroitin. Based on the previously published
      avian sequence, we searched the database of expressed sequence tags (dbEST) and
      obtained partial-length cDNAs that we completed by 5'-RACE using human
      chondrosarcoma and endothelial-cell RNA as template. Stable transfection of our
      full-length expression construct into CHO-K1 cells resulted in marked increases
      in C6ST and keratan sulfate sulfotransferase (KSST) enzymatic activities in cell
      homogenates. The predicted 411 amino acid sequence of human C6ST contains an N
      terminal hydrophobic domain consistent with membrane insertion, four potential
      sites for N-linked glycosylation, several consensus sequences for protein
      phosphorylation, and one RGD sequence. The human and chick C6ST cDNA share 51%
      nucleotide identity, 40% amino acyl identity, and 75% amino acyl conservation.
      The human C6ST gene structure has been elucidated and exhibits an intron-less
      coding region, and the gene has been mapped to human chromosome 11 by radiation
      hybrid panel mapping.

PMID- 9639684
TI  - New Escherichia coli WP2 tester strains highly sensitive to reversion by
      oxidative mutagens.
AB  - New Escherichia coli strains have been added to the WP2 mutagenicity test for the
      specific detection of oxidative mutagens. Strain IC203 derives from WP2
      uvrA/pKM101 and is highly sensitive to oxidative stress due to a deficiency in
      the OxyR function. Following exposure to t-butyl hydroperoxide (BuOOH) or
      menadione (MD), but not to 4-nitroquinoline 1-oxide (4NQO), strain IC203 (oxyR)
      shows increased mutability with respect to the oxyR+ parent. The advantage that
      the OxyR deficiency confers on IC203 strain in detecting oxidative mutagens is
      not obtained with strains deficient in either katG or ahpCF, two OxyR-regulated
      genes. Strain IC206, a derivative of WP2 uvrA carrying a deletion of the umuDC
      genes and deficient in the MutY glycosylase, has also been added to the WP2 test
      for the detection of SOS-independent mutations promoted by 8-oxoguanine lesions.
      Induction of these mutations was observed after treatment with BuOOH, but not
      after MD or 4NQO exposure. The two new strains, IC203 and IC206, can be useful
      for the screening of mutations resulting from oxidative stress as well as in
      studies on antioxidants preventing mutagenesis.

PMID- 9639685
TI  - The in vivo mutagenicity and mutational spectrum at the lacI transgene recovered
      from the spleens of B6C3F1 lacI transgenic mice following a 4-week inhalation
      exposure to 1,3-butadiene.
AB  - 1,3-Butadiene (BD) is carcinogenic and mutagenic in B6C3F1 mice. We determined
      the lacI mutant frequency and mutational spectrum in spleen following inhalation
      exposure to BD at levels that are known to induce tumors. B6C3F1 lacI transgenic
      mice were exposed to air or to 62.5, 625, or 1250 ppm BD for 4 weeks (6 h/day, 5
      days/week) and euthanized 14 days after the last exposure. BD increased the lacI
      mutant frequency in spleen at all levels of BD examined. In BD-exposed mice, an
      increased frequency of G:C-->A:T transitions occurred at non-5'-CpG-3' sites.
      Exposure to BD in B6C3F1 lacI transgenic mice also increased the frequency of
      base substitution mutations that occurred at A:T base pairs when compared to air
      controls. The increased frequency of specific mutations at G:C base pairs in
      spleen was not observed in our previous studies in bone marrow and indicates
      tissue-specific differences in the BD-induced mutational spectrum. These data
      demonstrate that in vivo transgenic mouse mutagenicity assays can identify tissue
      specific mutagenicity and mutational spectrum responses of genotoxic carcinogens
      at exposure levels that are known to induce tumors.

PMID- 9639686
TI  - In vivo antigenotoxic effects of dietary agents and beverages co-administered
      with urethane: assessment of the role of glutathione S-transferase activity.
AB  - Antigenotoxic effects and changes in glutathione S-transferase (GST) activity
      were assessed in mice after oral co-administration of urethane (URE) with aqueous
      extracts of dietary vegetables (carrot, spinach and cabbage), spices (cinnamon,
      pepper, cumin, clove and cardamom), tea and coffee. The results of the
      genotoxicity assay (micronucleus test) demonstrated dose-related antigenotoxic
      effects after URE was co-administered with aqueous extracts of vegetables,
      spices, tea and coffee. Inhibition of GST activity was observed 4 h after
      treatment with URE alone. Co-administration of URE with extracts of vegetables,
      coffee and spices resulted in dose-related attenuation of the inhibitory effect
      of URE on GST activity. However, tea had no effect on inhibition of GST activity
      by URE. Hence an association between antigenotoxicity and GST activity could not
      be established.

PMID- 9639687
TI  - The alkaline single-cell gel electrophoresis (SCGE) assay applied to the analysis
      of radiation-induced DNA damage in thyroid cancer patients treated with 131I.
AB  - The alkaline single-cell gel electrophoresis (SCGE or Comet) assay appears to be
      a promising tool for measuring DNA damage at the individual cell level in both in
      vitro and in vivo studies. To provide further data on the possible applicability
      of this assay in human biomonitoring studies, we have evaluated the eventual
      genetic damage induced by therapeutic exposure to 131I, by measuring the Comet
      length and the amount of DNA damage in peripheral blood leukocytes from a group
      of 28 thyroid cancer patients who received 131I sodium iodide via oral
      administration. Blood samples were taken just before the treatment and 1 week
      after it. From the results obtained after radioiodine therapy, a small increase
      in the Comet length and in the grade of DNA damage is observed; however, this
      increase is not statistically significant because of inter-individual variability
      and the variable responses before and after 131I treatment. Considering our
      previous studies showing significant increases in the frequency of cytogenetic
      damage (when measured as micronuclei) in patients treated with relatively low
      doses of 131I, the results obtained in the present work by using the Comet assay
      could indicate that 1 week after the exposure most of the radioiodine-induced DNA
      lesions, that can be detected with this assay, have already been repaired.

PMID- 9639688
TI  - Radioprotective effect of zinc aspartate on mouse spermatogenesis: a flow
      cytometric evaluation.
AB  - The radioprotective effect of zinc aspartate on spermatogonial cells of whole
      body irradiated mice was studied using flow cytometry. Adult male Swiss albino
      mice were treated with 30 mg/kg body weight of zinc aspartate 30 min before
      exposure to 0, 0.5, 1, 2 and 3 Gy of gamma-radiation. The animals were killed 7
      to 70 days postirradiation and the relative percentages of different germ cells
      were analyzed by flow cytometry. A significant increase (p<0.002, 0. 0001, 0.005
      and 0.008 for 0.5, 1, 2 and 3 Gy, respectively) in the relative percentage of
      spermatogonial (2C) population was observed in mice treated with zinc aspartate
      before exposure to different doses of gamma-radiation, compared to the irradiated
      controls on day 35 posttreatment. Also mean of each radiation dose of all the
      intervals studied showed a significant (p<0.03) increase in the relative
      percentage of spermatogonia. Despite the increase in the relative percentage of
      spermatogonia, the relative percentage of tetraploid cells (4C) remained higher
      in the zinc aspartate treated mice, compared to the irradiated controls. However,
      there was no change in the haploid populations viz. round (1C) and elongated (HC)
      spermatids of the zinc aspartate pretreated animals compared to irradiated
      controls. These data suggests that zinc aspartate pretreatment protects
      spermatogonia and tetraploid cells from radiation-induced cell killing.

PMID- 9639689
TI  - Genotoxicity of nitric oxide produced from sodium nitroprusside.
AB  - Induction of mutation and micronucleus (MN) formation by nitric oxide (NO) was
      investigated in mammalian cells using sodium nitroprusside (SNP) as a drug donor
      of NO. Results showed that the concentration of NO2- in the tested solution rose
      according to time- and concentration-exposure to SNP. The treatment of SNP (0.5-8
      micromol/ml with S9 or 2-8 micromol/ml without S9) induced a concentration
      dependent increase in the mutation frequency at the gpt gene locus in g12 cells
      and caused a 13- (-S9) to 25- (+S9) fold increase above the background level at
      the highest concentration. A statistically significant increase in the number of
      micronucleated binucleated cells (MNBN) was also observed in treated groups. MNBN
      per thousand, MN per thousand and the proportion of the multiple micronuleated
      cells increased in a concentration-dependent manner in the concentration range of
      SNP (0.5-4 micromol/ml with S9 or 2-8 micromol/ml without S9). Our results
      indicate that SNP, an NO releasing drug, is genotoxic in g12 cells.

PMID- 9639690
TI  - Induction of telomerase activity and chromosome aberrations in human tumour cell
      lines following X-irradiation.
AB  - Telomerase, a ribonucleoprotein enzyme, has been detected in immortalised cells
      and in majority of human cancers. Numerical and structural chromosome aberrations
      are commonly observed in tumour cell lines. To study the expression of telomerase
      and its influence on the formation of chromosomal aberrations, human colon
      carcinoma cell line (SW480) and human nonpolyposis colorectal carcinoma (HNPCC)
      cell lines (NA50600, NA59 and NA61) were exposed to 2 or 4 Gy X-rays. Increased
      telomerase activity was observed in all these cell lines at 24 h postirradiation
      and a 3 to 7 fold increase was seen at 4 Gy dose as detected by Telomere Repeat
      Amplification Protocol. Chromosomal rearrangements (dicentrics, translocations
      and breaks/fragments) analysed by Giemsa staining and chromosome painting were
      increased significantly following X- Quantitative fluorescence in situ
      hybridisation using a peptide nucleic acid telomeric probe to measure telomere
      length at irradiation chromosomal level revealed that all cell lines have very
      short telomeres in the range of 0.29 to 2.1 kb. Following X-irradiation, an
      increase in the chromosome end-to-end (telomere) associations was observed. The
      present results demonstrate that presence or upregulation of telomerase activity
      did not prevent the formation of chromosome aberrations and/or telomere
      associations in tumour cell lines after X-irradiation.

PMID- 9639691
TI  - In vitro antimutagenic and in vivo anticlastogenic effects of carotenoids and
      solvent extracts from fruits and vegetables rich in carotenoids.
AB  - The water insoluble residues of some carotenoid-rich fruits and vegetables, such
      as apricots, oranges, brussels sprouts, carrots, yellow-red peppers, and
      tomatoes, were sequentially extracted with n-hexane, dichloromethane, acetone,
      and 2-propanol, and solvent extracted materials were tested for inhibition of
      mutagenicities induced by aflatoxin B1 (AFB1), benzo[a]pyrene (BaP), 2-amino-3
      methylimidazo[4,5-f]quinoline (IQ), and cyclophosphamide (CP) in histidine
      deficient strains of Salmonella typhimurium. Antimutagenic activities were found
      in many extracts, but especially in the n-hexane extracts. For example, in the
      case of oranges, 100 microg of this extract reduced the bacterial mutagenicity of
      AFB1, BaP, CP and IQ by 72, 67, 53, and 27%, respectively. Separation by semi
      preparative HPLC of the n-hexane extracts of carrots, tomatoes, and oranges
      indicated that the antimutagenicity was mainly associated with the fractions of
      the hydrocarbon carotenoids (alpha-, beta-carotene, lycopene), the xanthophylls
      (beta-cryptoxanthin, lutein), and also the carotenolesters (oranges). When 16
      reference carotenoids were investigated as described above, the following results
      were obtained: In the case of BaP, antimutagenic activity, quantified by dose
      response curves, was exhibited by 8'-apo-beta-carotenal, alpha- and beta
      carotene, beta-cryptoxanthin, lutein, retinal, and retinol (ID50-values: 20-100
      nmol ml-1 top agar, 50-70% maximum inhibition at 1 micromol ml-1 top agar), while
      the maximum inhibition by torularhodin did not exceed 40%. Astaxanthin, 10'- and
      12'-apo-beta-carotenal, bixin, canthaxanthin, ethyl-8'-apo-beta-caro-ten-8'-oate,
      lycopene, and zeaxanthin were inactive or at best marginally active (<20%
      inhibition). Closely similar results were obtained with AFB1. The bacterial
      mutagenicity of CP was strongly reduced by alpha- and beta-carotene,
      canthaxanthin, and retinol (ID50-values: 67-112 nmol ml-1 top agar, 50-63%
      maximum inhibition at 1 micromol ml-1 top agar), moderately by beta
      cryptoxanthin, and lutein (45% and 28%, respectively), and only marginally or,
      not at all, by all remaining carotenoids. In the case of IQ, the carotenoids
      exhibited the weakest antimutagenic potency (7-43%, ID50-values of retinal and
      retinol: 160 and 189 nmol ml-1 top agar, 60% and 55% inhibition, respectively).
      The mutagenic activity of the proximal mutagen of IQ, N-OH-IQ, in S. typhimurium
      TA 98NR was not significantly reduced by any carotenoid tested. These
      observations as well as the inhibition of various cytochrome P-450 linked 7
      alkoxyresorufin-O-dealkylase activities (EROD, MROD, PROD) by four selected
      carotenoids (retinol>beta-cryptoxanthin>beta-carotene>lutein, IC50-values: 19-109
      microM), indicate that the inhibition of the metabolic activation of the
      different promutagens could cause antimutagenicity. Finally, it could be
      demonstrated that the number of BaP or CP induced micronuclei in polychromatic
      erythrocytes in bone-marrow of mice was reduced significantly by the carotenoids
      lycopene, canthaxanthin, lutein and beta-cryptoxanthin (25-46%). These results
      clearly show that carotenoids possess biological activities in vitro and in vivo
      distinct from their function as precursors of vitamin A or antioxidants
      suggesting effects on activation of promutagens.

PMID- 9639692
TI  - Efficient protection of cells from the genotoxicity of nitrosoureas by the
      retrovirus-mediated transfer of human O6-methylguanine-DNA methyltransferase
      using bicistronic vectors with human multidrug resistance gene 1.
AB  - Retrovirus-mediated transfer of O6-methylguanine-DNA methyltransferase (MGMT;
      E.C. 2.1.1.63) and a human multidrug-resistance gene (MDR1) confers resistance to
      nitrosoureas and natural product antitumor agents, respectively. In a previous
      study, we constructed two bicistronic retroviral vectors, Ha-MDR-IRES-MGMT and Ha
      MGMT-IRES-MDR, that allow co-expression of the MGMT gene and the MDR1 gene to
      protect cells from the toxicity of combination chemotherapy. Each cell transduced
      with Ha-MDR-IRES-MGMT or Ha-MGMT-IRES-MDR showed high-level resistance to
      vincristine and 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3
      nitrosou rea (ACNU), indicating that the two drug-resistance genes can be
      functionally co-expressed from these vectors. In the present study, we examined
      whether the expression of MGMT from these MDR1-MGMT bicistronic retroviral
      vectors could protect cells from the genotoxicity of nitrosoureas. Three
      independent Ha-MDR-IRES-MGMT-transduced clones and three independent Ha-MGMT-IRES
      MDR-transduced clones of HeLa MR cells showed 12-23-fold and 27-30-fold higher
      MGMT activity than the parental cells. These clones are more resistant to ACNU
      mutagenicity measured by the frequency of the emergence of 6-thioguanine
      resistant colonies after ACNU treatment over the frequency seen in the parental
      cells. The ACNU-induced sister chromatid exchange (SCE) was markedly suppressed
      in these clones. Murine bone marrow cells were transduced with either Ha-MDR-IRES
      MGMT or Ha-MGMT-IRES-MDR. Non-selected populations of the transduced cells showed
      only marginal increases in drug resistance and MGMT activity. Remarkable increase
      in drug resistance and MGMT activity were observed after a short exposure of the
      transduced cells to vincristine. The Ha-MDR-IRES-MGMT-transduced, vincristine
      selected bone marrow cells showed 27-fold resistance to vincristine, 7-fold
      resistance to ACNU, and 10-fold higher MGMT activity than the non-transduced, non
      selected cells. The Ha-MGMT-IRES-MDR-transduced, vincristine-selected cells
      showed 8-fold resistance to vincristine, 16-fold resistance to ACNU and 19-fold
      higher MGMT activity than the non-transduced, non-selected cells. The rates of
      ACNU-induced SCE in the vincristine-selected cells were as follows: non
      transduced cells (non-selected) and HaMDR-transduced cells>Ha-MDR-IRES-MGMT
      transduced cells>Ha-MGMT-IRES-MDR-transduced cells. Again, the only marginal
      levels of increases in the rates of ACNU-induced SCE were observed in non
      selected population of the transduced cells. These results indicate that the MDR1
      MGMT bicistronic retrovirus vectors would be useful to protect normal
      hematopoietic cells from nitrosourea-induced mutagenesis, and drug-selectable
      bicistronic constructs would have great advantage over non-selectable vectors.

PMID- 9639693
TI  - Induction of somatic DNA damage as measured by single cell gel electrophoresis
      and point mutation in leaves of tobacco plants.
AB  - The induction and measurement of DNA damage in nuclei of plant tissues is a new
      area of study with the alkaline single cell gel electrophoresis/comet assay.
      Methods to isolate plant cell nuclei cause high levels of DNA damage which are
      detected by the comet assay. We developed a method to isolate nuclei from leaf
      tissue of Nicotiana tabacum (a1+/a1; a2+/a2) in a modified Sorensen buffer that
      resulted in constant, low tail moment values for the negative controls. After
      treating intact tobacco plants with 1-8 mM ethyl methanesulfonate (EMS) we
      obtained a direct concentration-response with an average median tail moment of
      65.9+/-4.4 micro(m) for plants exposed to the highest EMS concentration as
      compared to the median control tail moment value of 4.1+/-0.8. We found that the
      highest resolution was obtained with electrophoretic conditions of 0.74 V/cm at
      300 mA for 20 min. Multiple leaves could be analyzed per plant within each
      treatment group and the tail moments were not significantly different. Tobacco
      seedlings were treated with EMS in the same manner as used for the comet assay
      and mutations were induced in the leaf primordia. The mean mutant frequency for
      the control was 1.46+/-0.20 mutant sectors/leaf. The mutant frequency increased
      in a concentration dependent manner; the mutant frequency induced by 8 mM EMS was
      37.89+/-2.37 mutant sectors/leaf. The comet tail moment values and the leaf
      mutant frequency were highly correlated (r=0.98). The genetic response factor was
      calculated by the ratio of the difference in the response within the linear
      portion of each concentration-response curve divided by the slope of the curve.
      The genetic response factor for the tail moment was 7.82 while the value for
      mutation induction was 7.76. In this paper we describe a sensitive method with
      high resolution to apply the alkaline comet assay to plant leaves. The comet
      assay response was compared to that of induced point mutation. With this
      sensitive method for nuclei isolation from plant leaves, the alkaline SCGE assay
      could be incorporated into in situ plant environmental monitoring.

PMID- 9639694
TI  - Involvement of oxidative stress in motorcycle exhaust particle-induced DNA damage
      and inhibition of intercellular communication.
AB  - In this study, we investigated the involvement of reactive oxygen species (ROS)
      in the motorcycle exhaust particle (MEP)-induced genotoxic and non-genotoxic
      activity in mammalian cell systems. Initially, the capability of MEP to induce
      ROS was evaluated by using 2',7'-dichlorofluorescin diacetate (DCFH-DA) to detect
      hydrogen peroxide (H2O2). A five-fold increase in H2O2 was observed in Chinese
      hamster lung V79 and human lung carcinoma Calu-1 cells treated with 100 microg/ml
      MEP for 2 h. Under the same experimental conditions, only a two-fold elevation in
      H2O2 was detected in hepatic cell systems such as BNL.Cl.2, HepG2, and Hep3B.
      Treatment of the V79 cells with varying concentrations of MEP caused a dose
      dependent increase in sister chromatid exchanges (SCEs), which are effectively
      inhibited by addition of antioxidants, N-acetyl-l-cysteine (NAC) and ascorbic
      acid. Furthermore, we determined the oxidized bases in the V79 cells after
      exposure to MEP. The result showed that 500 microg/ml MEP induced a 3.7-fold
      increase in thymine glycol (TG) and a seven-fold increase in 8-hydroxy-guanosine
      (8-OHGua) as compared to untreated cells. We subsequently examined whether MEP
      would affect gap junctional intercellular communication (GJIC), a tumor promotion
      process, in V79 cells. We found that MEP inhibited GJIC in a dose-response
      fashion. Maximal inhibition occurred at 500 microg/ml. The concentration that
      inhibited at 0.5 of the fraction of the control was 200 microg/ml. Interestingly,
      when cells were pretreated with NAC or ascorbic acid, they could abolish the MEP
      mediated inhibition of GJIC. In addition, a moderate decrease of glutathione was
      observed in the V79 cells during exposure to MEP. Taken together, our findings
      suggest that MEP can induce oxidative stress in a broad range of cell lines,
      especially in lung cell systems. The MEP-induced oxidative stress was critically
      involved in both genotoxic and non-genotoxic activity.

PMID- 9639695
TI  - C-mitotic effects of trichloroethylene (TCE) on bone marrow cells of mice.
AB  - The possible aneuploidy inducing activity of Trichloroethylene (TCE, CAS No. 79
      01-6) an industrial chemical was investigated by employing three cytogenetic end
      points i.e., C-mitotic effects, Micronuclei (MN) and parallel chromosome
      structural aberration (CA) analysis in vivo. The experiments were conducted in
      mouse bone marrow cells. The animals were treated with TCE in the dose of 500,
      1000, 2000 and 4000 mg/kg for 6, 12, 24, 48 hr. Colchicine (COL) was taken as
      positive control for its known aneuploidy-inducing effects and Cyclophosphamide
      as a model mutagen. TCE showed positive CM effects accompanied with increases of
      Mitotic Index and decreased frequencies of anaphases in higher doses. The
      chemical showed a positive MN response in bone marrow polychromatic erythrocytes
      but was negative in CA analysis. The preliminary results indicated that TCE is
      capable of inducing C-mitotic effects in mouse bone marrow cells which is
      suggestive of its possible aneuploidy induction potential.

PMID- 9639696
TI  - Comparative mutational spectra of the nitrogen mustard chlorambucil and its half
      mustard analogue in Chinese hamster AS52 cells.
AB  - Nitrogen mustards play an important role in current cancer chemotherapy. The most
      effective antitumour agents are those carrying two alkylating functions, probably
      through their ability to form interstrand cross-links in DNA. Such lesions appear
      to create more of a block in DNA replication and are more difficult to repair
      than are most monoadducts. Although there were early reports that monofunctional
      drugs were more mutagenic than the bifunctional drugs, this has not been formally
      proved using structurally related drugs in a mutagenicity assay capable of
      detecting a range of different events. We have studied both the mutagenic potency
      and spectrum of events caused by treatment with the clinical agent, chlorambucil,
      compared with its half-mustard analogue, in Chinese hamster ovary (CHO)-AS52
      cells. Although both drugs caused comparable increases in mutation frequency at
      doses killing 90% of cells (from around 9x10-6 to around 9x10-5 mutant cells),
      the nature of events differed significantly between the drugs. By far the
      majority of mutations caused by the half-mustard were transversion mutations, and
      almost all of these could be interpreted in relation to the DNA adducts that are
      known to be formed. In contrast, the majority of chlorambucil-induced mutations
      were major deletions, and point mutations were only identified from a few clones.
      Parallel micronucleus assays verified that chlorambucil has a stronger ability to
      break chromosomes than the half-mustard. These two drugs are thought to form
      similar monoadducts, but only the full mustard can form interstrand cross-links.
      The data suggest that DNA cross-links, although only a minor fraction of the
      total lesions, dominate the mutagenic spectrum and lead to gross changes at the
      chromosome level that can not be readily associated with individual lesions
      produced by the drug.

PMID- 9639697
TI  - In vitro investigation of toxaphene genotoxicity in S. typhimurium and Chinese
      hamster V79 lung fibroblasts.
AB  - The polychlorinated pesticide toxaphene has been identified as a persistent
      environmental contaminant and is of particular concern in the Great Lakes and
      Arctic regions of Canada. Inconsistencies in published in vitro genotoxicology
      studies have hindered risk assessments of toxaphene exposure. When toxaphene
      mutagenicity was re-evaluated in the Ames Salmonella/microsome assay at 10-10,000
      microg/plate, a dose-dependent increase in His revertants occurred in all five
      strains of S. typhimurium tested (TA97, TA98, TA100, TA102 and TA104) with higher
      mutation frequencies observed in the absence of S9 metabolic activation. However,
      the mutagenic potential of toxaphene was relatively low with concentrations
      greater than 500 microg/plate required to induce mutation. Toxaphene genotoxicity
      was also examined in a mammalian system using Chinese hamster V79 lung
      fibroblasts with metabolic activation provided by human HepG2 hepatoma cells.
      Genotoxicity of 1-10 microg/ml toxaphene was examined by measuring the frequency
      of sister chromatid exchange (SCE) and mutation induction at the hypoxanthine
      guanine phosphoribosyl transferase (HGPRT) gene locus. Although small increases
      in SCE were observed at toxic concentrations of toxaphene approaching the LD50
      (10 microg/ml), they were not found to be statistically significant relative to
      control. Toxaphene was also unable to induce HGPRT mutagenesis at the
      concentrations tested. These results show that while toxaphene is a weak, direct
      acting mutagen in the Ames Salmonella Test, convincing evidence of dose-dependent
      SCE induction and mutagenicity at the HGPRT gene locus could not be demonstrated
      in V79 cells.

PMID- 9639699
TI  - Increased sister chromatid exchange and chromosomal aberration frequencies in
      psychiatric patients receiving psychopharmacological therapy.
AB  - Combinations of various psychotropic drugs are often used, sometimes for long
      periods, in the treatment of various forms of psychiatric disorders. This paper
      evaluates the cytogenetic consequences of daily exposure to polytherapy with
      antianxiety, antipsychotic and antimaniacal drugs by determining chromosomal
      aberrations (CA) and sister chromatid exchange (SCE) in peripheral blood samples.
      The study was performed with a group of 36 psychiatric patients: 18 receiving
      long-term treatment with lithium carbonate, combined with benzodiazepines (BD)
      and antipsychotic agents (Group A) and 18 treated with BD and antipsychotics
      (Group B). Among the latter, 7 patients had only been treated for 1 month (Group
      B1). The results reveal a significant increase (p<0.01) in cells with aberrations
      in the two groups of patients (A,B) compared to controls. Moreover, complex
      aberrations (dicentrics, rearrangements, chromatid exchanges) had a frequency of
      0.63% in patients receiving long-term treatment compared to 0.11% in controls,
      corresponding to the general spontaneous rate. The mean frequency of SCE/cell and
      the percentage of cells with a high frequency of exchanges (HFC) also showed a
      highly significant difference compared to controls in both Group A and Group B.
      Group B1 (patients who only commenced treatment 1 month earlier) did not differ
      from the control group with regard to the frequency and type of chromosomal
      aberration or in relation to the mean frequency of SCE/cell. No significant
      differences were detected between Groups A and B both of which showed similar
      frequencies of cells with aberrations, SCE/cell and HFC. No correlations were
      observed in Group A between lithemia and the biological markers studied.

PMID- 9639698
TI  - Comparison of in vivo mutagenesis in the endogenous Hprt gene and the lacI
      transgene of Big Blue(R) rats treated with 7, 12-dimethylbenz[a]anthracene.
AB  - The lacI transgene of Big Blue(R) (BB) rats was evaluated as a reporter of in
      vivo mutation by comparing mutant frequencies (MFs) in it and in the endogenous
      Hprt gene. Seven-week old female BB rats were given single doses of 0, 20, 75 and
      130 mg/kg of 7, 12-dimethylbenz(a)anthracene (DMBA) by gavage, and Hprt and lacI
      MFs in splenic lymphocytes were measured over a period of 18 weeks. The Hprt MFs
      in treated rats increased for 10 weeks and then declined; 130 mg/kg of DMBA
      produced a maximum Hprt MF of 168+/-11.4x10-6 clonable lymphocytes, while the MF
      in control rats was 7.4+/-1. 5x10-6. DMBA exposure of generic F344 rats resulted
      in a similar time-course of mutant induction but produced about 50% higher Hprt
      MFs with the 75 and 130 mg/kg doses. In contrast, the lacI MFs increased for 6
      weeks and then remained relatively constant; 130 mg/kg of DMBA produced a maximum
      increase in lacI MF of 341+/-83x10-6 PFU compared with 25+/-5x10-6 PFU in control
      rats. The Hprt mutant frequencies in DMBA-treated BB and F344 rats were
      significantly increased over control values for every dose-time combination
      examined, while only the 130 mg/kg dose consistently produced lacI MFs that were
      significantly above the controls. In addition, the fold-increase in MF for
      treated vs. control rats was two times higher for the Hprt gene than the lacI
      gene due to the higher MFs in the lacI gene of control rats. Differences between
      the lacI and Hprt genes in the kinetics of mutant induction, in the frequency of
      induced mutants, and in the sensitivity of mutant detection could be explained at
      least partially by the properties of these two genes.

PMID- 9639700
TI  - Mutagenic interactions between X-rays and two promutagens, o-phenylenediamine and
      N-nitrosodimethylamine, in the stamen hairs of Tradescantia clone BNL 4430.
AB  - Mutagenic interactions between X-rays and two promutagens, o-phenylenediamine
      (PDA) and N-nitrosodimethylamine (DMN), were studied in the stamen hairs of
      Tradescantia clone BNL 4430, a blue/pink heterozygote. The young inflorescence
      bearing shoots with roots of this clone cultivated in a nutrient solution
      circulating growth chamber were used as tester plants. After determining dose
      response curves for X-rays. PDA and DMN, combined treatments with PDA or DMN and
      X-rays were conducted, exposing acutely to X-rays 20 h before starting, at the
      midpoint of, or 20 h after completing the PDA or DMN treatments for 4 h. Clear
      synergistic effects in inducing somatic pink mutations were detected when X-rays
      were irradiated before the PDA or DMN treatments, resembling those confirmed
      earlier between maleic hydrazide (MH) and X-rays. On the contrary, clear
      antagonistic effects were observed when X-rays were given after the PDA or DMN
      treatments, also resembling those between MH and X-rays. When X-rayed at the
      midpoint of the PDA or DMN treatments, merely additive and synergistic effects
      were observed, respectively, differing from the antagonistic effects between MH
      and X-rays. The mutagenic synergisms detected were considered to be the results
      of interactions between DNA strand breaks (and the resultant chromosome breaks)
      induced by X-rays and those by PDA or DMN, whereas the mutagenic antagonisms
      observed were presumed to be due to X-ray-caused inhibition of the activation of
      PDA and DMN in the stamen-hair cells. The time periods required for penetrations
      into floral tissues and/or activations into mutagens seem different among PDA,
      DMN and MH.

PMID- 9639701
TI  - High and low UV-dose responses in SOS-induction of the precise excision of
      transposons tn1, Tn5 and Tn10 in Escherichia coli.
AB  - UV-inducible precise excision of transposons is a specific SOS-mutagenesis
      process. It deals with the deletion formation which has previously been
      demonstrated to involve direct or inverted IS-sequences of transposons. The
      process was used for revisiting the targeted and untargeted SOS-mutability and
      its relationship to the key genes for SOS-mutagenesis: the recA, lexA and umuDC.
      The precise excision of transposons Tn5 and Tn10 from the chromosomal insertion
      sites ade128 and cyc750 is induced in Escherichia coli K-12 and B cells, wild
      type for DNA-repair, both by the low doses of UV-light ranging from 0.25 J m-2 to
      2.5 J m-2 and the high doses within the range 5.0-40.0 J m-2. Precise excision of
      these transposons induced by the range of low doses incapable to induce targeted
      point mutations reveals its mostly untargeted nature. This process for the
      transposon Tn1 is not induced by UV-light within the range of doses 0.25-2.5 J m
      2 while its induction is possible by UV-fluences ranging from 5.0 to 40.0 J m-2.
      A dose-response of the precise excision of Tn1 is similar to that of the UV
      induced reversion of trpUAA point mutation that is targeted by nature and
      contrasts to the UV-inducible precise excision of Tn5 and Tn10. Both types of UV
      inducible precise excision, demonstrated either by Tn1 or Tn5 and Tn10, are
      eliminated by mutations in the lexA, recA and umuDC genes indispensable for UV
      induced SOS-mutability. The palindromic structures different for the transposons
      Tn1, Tn5 and Tn10 are discussed to be involved and affect the targeted and
      untargeted precise excision of transposons induced by UV-light.

PMID- 9639702
TI  - Induction of micronuclei in the domestic cat (Felis domesticus) peripheral blood
      by colchicine and cytosine-arabinoside.
AB  - One advantage of bioassays over other kinds of tests is the processing or
      metabolism of the compound by the organism. In a previous work, in which we
      reported the number of micronucleated erythrocytes (MNE) in the peripheral blood
      of 35 species, the cat was one of the species with the highest number of
      micronuclei (MN). Cats have a low level of circulating polychromatic erythrocytes
      (PCE), i.e. 0.05%, which is much lower than in the laboratory mouse, but higher
      than in species such as cows, donkeys, sheep, goats and horses. Thus, MN were
      scored in total blood erythrocytes. In the present work, we assess the cat as a
      test system for MN induction. Three doses of a colchicine-cytosine arabinoside
      mixture were administered to young cats during 4 days; then, the numbers of MNE
      in blood collected before the first injection and 48 and 96 h later were
      compared. The number of MNE increased with time, reaching the highest values in
      the samples taken 96 h after the administration of the micronucleogenic agents.

PMID- 9639703
TI  - Genotoxic activity of four inhibitors of DNA topoisomerases in larval cells of
      Drosophila melanogaster as measured in the wing spot assay.
AB  - Four inhibitors of DNA topoisomerases namely nalidixic acid, camptothecin, m
      amsacrine and etoposide, have been evaluated for genotoxic effects in the wing
      spot test of Drosophila melanogaster. This assay assesses somatic recombination
      and mutational events. We studied nalidixic acid as an inhibitor of bacterial DNA
      gyrase, camptothecin as a topoisomerase I inhibitor, as well as m-amsacrine and
      etoposide as topoisomerse II inhibitors. The genotoxic effects were determined
      from the appearance of wing spots in flies trans-heterozygous for the recessive
      markers multiple wing hairs (mwh) and flare, as well as in flies heterozygous for
      mwh and the multiply inverted TM3 balancer chromosome. From our results it
      appears that whilst nalidixic acid and m-amsacrine were compounds that did not
      increase the incidence of mutant clones, camptothecin and etoposide proved to be
      significantly genotoxic in this test, being camptothecin more effective than
      etoposide. A significant proportion of the total spot induction was due to
      mitotic recombination, confirming previously reported data. On the other hand,
      the cotreatments of each topoisomerase inhibitor with the alkylating agent ethyl
      methanesulfonate (EMS) indicate that, while nalidixic acid, m-amsacrine and
      etoposide show a tendency to an antagonistic interaction, camptothecin shows an
      additive effect, suggesting mechanistic differences between the activity of the
      four inhibitors of DNA topoisomerases studied.

PMID- 9639704
TI  - Cytogenetic study on children living in Southern Urals contaminated areas
      (nuclear incidents 1948-1967).
AB  - As a result of the activities of the first Soviet plutonium production reactor,
      large territories of the Southern Urals were exposed to radioactive
      contamination. Three different incidents occurring between 1948 and 1967 lead to
      major exposure. A total of 280,000 people residing on the contaminated
      territories were exposed both to external and internal contamination particularly
      due to the long-lived radionuclides 137Cs and 90Sr. The highest doses were
      received by 28,000 people living on the Techa riverside villages. In the present
      paper 15 presumably exposed children coming from the Muslyumovo village on the
      Techa river have been analyzed using conventional cytogenetic procedure in order
      to assess a radiation-induced damage. The data obtained have been compared to a
      group of matched unexposed controls. The results show a statistical difference
      between the two cohorts which suggests a possible residual contamination
      representing a continuous hazard for the new generations.

PMID- 9639705
TI  - Characterization of gamma irradiation-induced deletion mutations at a selectable
      locus in Arabidopsis.
AB  - Seeds of transgenic Arabidopsis, containing a negatively selectable suicide
      marker, a 35Stms2 construct introduced as a transgene, were gamma-irradiated at a
      range of doses from 20-120 krad. Batches of M2 seeds, from M1 plants irradiated
      at doses of 40, 45 and 60 krad, were screened by germinating them on medium
      containing NAM under conditions that selectively inhibited growth of plants
      expressing the tms2 gene product. Nine candidate loss-of-transgene mutants were
      isolated. The frequency of such mutations (0.0125 to 0.025%) did not vary
      significantly with irradiation dose or M1 pool size. DNA from the mutants and the
      parent was hybridized in Southern blots, using probes complementary to various
      regions of the transgene. All nine mutants were null for both the tms2 coding
      sequence and the 35S promoter. Six of the nine mutants were null for the entire
      transgene construct of 9 kbp. DNA from one mutant contained one of the T-DNA
      borders and gave a hybridization pattern consistent with a deletion at least 5
      kbp. The two remaining mutant lines gave identical patterns of hybridization,
      consistent with a 5.6-kbp internal deletion within the transgene. From the
      Southern blots, and on the basis of lineage, the nine lines represent the progeny
      of either seven or eight independent mutations. We have established conditions
      capable of producing deletion mutations of at least 5 kbp, but without apparently
      introducing small deletions or rearrangements. Such deletion mutations are
      ideally suited for cloning by subtractive hybridization, and should also be
      readily detectable by RFLP analysis, facilitating map-based cloning procedures.

PMID- 9639706
TI  - [Development of tertiary disciplines in otorhinolaryngology].

PMID- 9639707
TI  - [The cochlea in short-term culture].
AB  - In order to establish organotypic culture of the cochlea, the dissection of the
      early postnatal mouse cochlea and its morphology in short-term culture were
      investigated. The viability of hair cells in the culture was assessed using
      differential interference contrast (DIC) microscopy and double-staining with
      fluorescein diacetate (FDA) and propidium iodide (PI). The hair cells remained
      viable and did not show any signs of damage for up to 8-18 hours. When incubated
      in Hank's solution containing 1 mmol/L dihydrostreptomycin, the hair cells
      initially deteriorated in 0.5-4.5 hours and progressed to entire degeneration
      after 10-20 hours. In addition to its utilization in organotypic culture, the
      cochlea in short-term culture can be used as a valuable model for studying
      cellular and molecular neurobiology of the inner ears.

PMID- 9639708
TI  - [Effect of epidermal growth factor and dexamethasone on blast hearing loss].
AB  - The expression of epidermal growth factor receptor (EGFR) in cochlear hear cells
      was studied in normal and guinea pigs exposed to blasts. The effects of epidermal
      growth factor (EGF) and dexamethasone (DXM) treatment for blast hearing loss and
      the underlying mechanisms were also explored. Scattered expression of EGFR was
      seen in IHCs and OHCs in normal guinea pigs. Segmentally distributing positive
      reaction was also located in stereocillia of hair cells. Distribution of EGFR
      reaction was seen in the cytoplasm of IHC 24 hours after exposure to blasts, and
      in the stereocillia of IHC and the cuticular plate of OHC 72 hours postexposure.
      At one week EGFR reaction in hair cells increased obviously and part of OHC
      stereocillia also showed positive reaction. EGFR reaction reduced at two weeks,
      though positive reaction could still be found in the stereocillia of hair cells
      at one month. Combination of EGF and DXM administrations promoted hearing
      recovery significantly. Our results suggest that healing of injured hair cells
      may be to EGF.

PMID- 9639709
TI  - [Computer image analysis in the study of endolymphatic hydrops].
AB  - In search for an objective method to be used to judge the extent of hydrops,
      computer image analysis system was used in the study on guinea pig endolymphatic
      hydrops. The image information of the whole cochlea was collected, then the
      length of Reissener's membrane and section area of scala media were calculated
      based upon parameters such as ratio factors and point values. The results were as
      follows: 1) Hydrops observed with light microscope had no statistical difference.
      2) Within 55 days postoperatively, the hydrops grew more obvious with time. 3)
      The hydrops was more extensive in the basal turn than in the apical turn, though
      more conspicuous cytopathologic change was found in the apical turn. The
      conclusions: 1) The current technique is objective, accurate and reliable. 2)
      Both the length of Reissener's membrane and section area of scala media can be
      used to measure the extent of hydrops.

PMID- 9639710
TI  - [Dynamic effects of sulphuric gentamicin on vestibular function in guinea pigs].
AB  - Sinusoidal rotation and rotational stimulation tests were used to examine
      vestibular function in guinea pigs. The results showed that there was no
      statistically significant difference in the mean number of nystagmus of semi
      cycle sinusoidal rotation test and the duration of nystagmus of rotational
      stimulation test for both the control and test groups before treatment in albinos
      and pigmented guinea pigs. Meantime, daily subcutaneous injection of gentamicin
      125 mg/kg body weight for 12 days in albinos and pigmented guinea pigs showed no
      significant change in vestibular function until the 7th day of treatment.
      Significant impairment of vestibular function was noticed on the 10th treatment
      day. At 5 days after treatment vestibular impairment reached its maximum and
      minimal recovery was seen at 14 days after treatment. No Further improvement of
      vestibular function was noticed three months after treatment. The methods are
      feasible and reliable.

PMID- 9639711
TI  - [Failure in mastoidectomy with posterior canal wall preservation and
      tympanoplasty case analysis].
AB  - Preservation of the posterior canal wall in mastoidectomy is essential for
      rebuilding normal tympanum and conductive structures, and has been widely
      recommended. However, controversies remain about the technique due to its
      complications and diverse results reported. This paper analysed the causes of
      four failed cases in detail and proposed measure to reduce morbidities and
      promote success. The review includes case selection, operation staging, surgical
      techniques and lesion removal etc.

PMID- 9639712
TI  - [Vestibular and auditory functions in Meniere's disease].
AB  - This paper is, aiming at understanding disturbances of and correllation between
      colchear and vestibular functions in Meniere's disease. Auditory and vestibular
      functions in 121 Meniere cases (70 males and 51 females, age ranging from 19 to
      63 years), diagnosed according to the AAO-HNS criteria, were analysed. The
      results were as follows: 1)There was positive correlation between semicircular
      canal paresis and hearing impairment. 2) There was statistically significant
      positive correlation between hearing impairment and the -SP/AP ratio. 3) There
      was statistically significant correlation between hearing impairment and glycerin
      test result, the rate of positive result being higher in those with advanced
      hearing loss than in those with mild loss. 4) There was correlation between the
      rate of positive glycerin test result and audiogram configuration. The rate with
      rising audiogram pattern was higher than with that falling pattern (69.0% vs
      33.3%). It was also found that ECochG was far more effective than glycerin test
      in diagnosing Meniere's disease. The physiologic basis and significance of ECochG
      and glycerin test in Meniere's disease were discussed.

PMID- 9639713
TI  - [Endoscopic surgery of the cerebellopontine angle].
AB  - Twenty-four patients with various cerebellopontine angle (CPA) disorders
      including hemifacial spasm (11 cases), trigeminal neuralgia (9 cases),
      glossopharyngeal neuralgia (2 cases) incapacitating vertigo and acoustic neuroma
      (one case each), were treated by endoscopic surgery, via the retrosigmoid
      approach. Because of the distal light and panoramic view, the endoscope provides
      an excellent view inside the CPA, allows clear identification of the vascular and
      nervous components, and is especially helpful in cases of trigeminal neuralgia
      and hemifacial spasm to find the location of cross-conflict. Under the monitor of
      endoscope, the surgeon is able to perform facial nerve decompression and
      splitting, selective trigeminal nerve root and glossopharyngeal nerve section
      with ease and safty. The present study shows that the endoscopic surgery is a
      simple and useful procedure which helps to reduce surgical complications. We
      recommend the application of endoscopy in the management of CPA disorders.

PMID- 9639714
TI  - [Anatomy of the endolymphatic sac and its clinical significance].
AB  - Using 28 formalin fixed temporal bones and materials of 26 cases of endolymphatic
      surgery for menieres' disease, the location, vascular distribution and size of
      the endolyphatic sac (ELS) were investigated. ELS were measured with surgical
      microscope in all the cadaver specimen with a mean length of 6.9393 +/- 2.0429 mm
      and mean width of 5.8821 +/-1.6522 mm. All the specimens showed no clear
      capillary distribution. Only in 24 of the 26 ELS surgeries for Menieres' disease
      the ELS were found. The mean length was 6.8125 +/- 2.2449 mm, the mean width
      5.6666 +/- 1.5084 mm and the vascular distribution was unclear in 29% of the
      cases. It was found that the ELS usually located at the Donaldson line, and moved
      downward in the under-developed mastoid with smaller size.

PMID- 9639715
TI  - [Cluster epithelial cells in nasal secretions of allergic rhinitis and its
      relation to eosinophils].
AB  - The cytology of nasal secretions in 20 patients with allergic rhinitis and 15
      patients with chronic maxillary sinusitis was investigated with transmission
      electron microscope to study the ultrastructure of the cluster epithelial cells
      in nasal secretions of allergic rhinitis. The results showed that the cluster
      epithelial cells were predominant cellular element in allergic nasal secretions.
      The number of cluster cells correlated positively with the number of eosinophils
      and the levels of eosinophilic cationic protein. It is suggested that the
      exfoliation of cluster nasal epithelial cellular elements may be caused by
      eosinophic cationic protein with resultant hyperreactivity of nasal mucosa.

PMID- 9639716
TI  - [Estradiol receptors expression in nasal polyps and its significance].
AB  - Nasal polyps are generally considered as a result of extreme nasal mucosal edema
      induced by long-term recurrent inflammation of the respiratory mucosa. The
      estradiol (E2) has been demonstrated to play a facilitating role in nasal
      inflammation. To evaluate the effect of estradiol on the pathogenesis of nasal
      polyps, the expression of E2 receptors in paraffin section from patients with
      nasal polyps (84 cases), chronic hypertrophic rhinitis (6 cases) and healthy
      control subjects were investigated by means of immunohistochemistry for E2
      receptors and toluidine blue staining for mast cells. It was shown that there was
      high expression of E2 receptors in 61 out of 84 cases (male 40, female 44) of
      nasal polyps and the expression distributed equally among both sexes. Low
      expression of E2 receptors presents in 2 out of 6 cases of chronic rhinitis and 1
      out of 4 healthy subjects. Noteworthily, the E2 receptor expressing cells are
      similar with the mast cells in shape and distribution. The authors speculate that
      they may be identical cells. E2 receptor expression in nasal polyps suggests that
      estradiol plays certain role in the development of nasal polyps.

PMID- 9639717
TI  - [Metastatic potential correlates with cell surface carbohydrate profiles of
      nasopharyngeal carcinoma].
AB  - In order to investigate the changes in glycoprotein structure between non
      metastatic and metastatic cells of nasopharyngerl carcinoma (NPC), peanut
      agglutinin (PNA), ulex europeaus (UEA-I) and concanavalin ensifomis agglutinin
      (ConA) staining were used to examine 102 nasopharyngeal carcinoma tissues (84
      primary tumors and 18 metastatic lymph nodes) with the avidin-biotinperoxidase
      complex method. PNA reaction was positive in most cells of nasopharyngeal
      carcinomas regardles of in histopathologic type, the degree of differentiation
      and metastasis. The levels of UEA-I receptors apparently increased during
      nasopharyngeal carcinoma progression from non-metastatic to metastatic tumors.
      The binding to ConA clearly decreased in the cells of metastatic cases and
      metastatic lymph node. So, the increased expression of UEA-I receptors and
      decrease of ConA receptors on tumor cells might have been implicated in the
      expression of metastatic potential.

PMID- 9639718
TI  - [Influence of HPD on immunological functions in patients with nasopharyngeal
      carcinoma treated by radiotherapy].
AB  - Seventy-eight patients with nasopharyngeal carcinoma were equally divided into
      two groups: 39 patients were treated by HPD plus radiation and 39 patients by
      radiation alone. Immunological functions were evaluated in each patient before
      and after radiation. The results showed that (1) in patients treated by RPD and
      radiation, no statistical difference was observed on immunological functions
      before and after treatment; (2) in patients treatd by radiation alone, the
      immunological functions, including OKT3, OKT4, OKT4/OKT8 ratio and lymphocyte
      transformation, were significantly decreased after treatment. These findings
      indicate that the immunological functions in patients with nasopharyngeal
      carcinoma could be protected by HPD during radiotherapy.

PMID- 9639719
TI  - [Induction of apoptosis by expression of retroviral mediated wild type p53 gene
      in laryngocarcinoma cell line].
AB  - The p53 gene is one of the most common targets for genetic abnormalities in human
      laryngocarcinoma. In this report, the ability of wild-type p53 gene to induce
      apoptosis of laryngocarcinoma cell was examined. The wt-p53 gene recombinant
      retroviral vector was constructed and the PA317 packaging cell line producing
      virus established. The recipient cell lines of Hep2 (laryngocarcinoma) containing
      the abnormal p53 gene were transfected in vitro with 1 ml fresh retroviral stock
      produced by the PA317. Southern-blot and Northern-blot were performed using the
      probe (1.7 Kb p53 cDNA). Assays for in vitro growth characteristics were
      performed. The result showed that introduction of wt-p53 greatly suppressed in
      vitro cellular growth of the laryngocarcinoma cell line and identified that the
      wt-p53 gene mediated the process of cell apoptosis. In conclusion, the retroviral
      vector-mediated wt-p53 gene transfer appeared to be able to induce the apoptosis
      in human laryngocarcinoma bearing multiple genetic lesions. The observation
      strongly suggests that inactivation of the p53 gene plays a significant role in
      the pathogenesis of laryngocarcinoma.

PMID- 9639720
TI  - [Epidermal growth factor receptor expression in laryngeal cancer].
AB  - The expression of epidermal growth factor receptor (EGFR) in 60 laryngeal
      carcinoma and 20 normal laryngeal mucosa was studied with immunohistochemical
      LSAB (labelled streptavidin biotin) method to elucidate its role in tumor
      progression. EGFR was negative in all 20 normal laryngeal mucosa specimens, and
      it was positive in 44 of 60 laryngeal carcinoma specimens. The expression of EGFR
      did not correlate with tumor location, tumor stage and lymph node metastasis, but
      correlated significantly with histological grading and the survival rate. A
      significantly higher positive rate was found in poorly differentiated than in
      moderately well differentiated tumors. The 3-year survival rate in patients with
      expression of EGFR was much lower than those with negative results (P < 0.01).
      The results suggest that EGFR may play an important role in the process of
      carcinogenesis in laryngeal mucosa and be used as a useful marker for the
      assessment of biological behavior and prognosis of laryngeal carcinoma.

PMID- 9639721
TI  - [Bi-pedical and bi-muscle flap reconstruction of the laryngeal function].
AB  - The method of reconstruction of laryngeal function by bi-pedical and bi-muscle
      flap (DP-DMF) was presented. The DP-DMF was obtained from sternohyoid muscle,
      sternothyroid muscle and thyrohyoid muscle. It had enough length, width and
      plasticity, applicable to all patients with T3 and T4 laryngeal carcinoma. Up to
      now, 102 patients were treated by expanded horizontal hemilaryngectomy and
      repaired with unilateral or bilateral DP-DMF. After operation, the swallow
      function returned to normal in 7 to 11 days. The tracheal tube extraction rate
      was 66.7% (72/108). The 5-year survival rate was 76.5% (62/81), and recurrence
      rate was 13.9% (15/108). With the application of DP-DMF, the patients who might
      have been treated formerly by total laryngectomy could be treated by partial
      laryngectomy. This method expanded the indication of partial laryngectomy,
      improved the life quality and survival rate.

PMID- 9639722
TI  - [A study on activity of beta-glucuronidase in serum and secretion from upper
      respiratory tract in patients with head and neck malignant tumors].
AB  - Beta-glucuronidase (beta-GD) activity in serum and upper respiratory tract (URT)
      secretion in patients with head and neck malignant tumors (HNMT) was studied.
      Subjects included 40 HNMT patients, 40 healthy volunteers and 40 patients with
      benign tumors of the head and neck region. The results showed that there was no
      statistically significant difference of serum beta-GD level among the three
      groups. The same was true for URT secretion between the normal control and benign
      tumor groups. beta-GD level in URT secretion was higher in HNMT group than in
      other groups (P < 0.001). Using healthy subjects' average beta-GD level plus two
      standard difference as positive standard, the sensitivity, reliability and
      specificity of the test were 85.0%, 92.5% and 100% respectively. beta-GD levels
      were higher in patients with advanced tumors and metastases. One year follow-ups
      of six patients showed that beta-GD level change in URT secretion was in
      accordance with clinical manifestations. These results suggest that assay of beta
      GD level in URT secretion can be used as a valuable supplimental parameter in
      early diagnosis of HNMTs, their clinical staging, evaluation of therapeutic
      effectiveness and detection of recurrence and metastases. In addition, this
      method has the advantage of easy, prompt, result specificity, sensitivity and
      reliability.

PMID- 9639723
TI  - [Vaginal template implant for cervical carcinoma with vaginal stenosis].
AB  - OBJECTIVE: For cervical carcinoma patients with poor geometry for conventional
      intracavitary radiotherapy, a simple vaginal template for interstitial
      implantation as a substitute was used. This is a report of the treatment results.
      METHODS: Patients with vaginal stenosis were treated over from July 1987 to June
      1991 with this vaginal template implant as part of the treatment. The applicator
      consisted of a front piece and an end piece. Holes were drilled in the front
      piece to guide the implantation of the cervix or vaginal vault. The diameter of
      applicators varied from 2.0 cm to 3.5 cm. Depending on the diameter of the
      applicators, six to eight needles on the periphery, or eight peripheral plus one
      central needle were used. The activity of the needles were around 8 mCi with a
      total length of 5.5 cm. The end piece was locked onto the front piece by a
      bayonet-type locking device. The purpose of the end piece was two-fold: to make
      up the length of the whole applicator to fit the vagina and to keep the implanted
      needles in place without being extruded. The implantation was performed under
      general anesthesia. RESULTS: One of the twelve patients treated with the vaginal
      template implant for vaginal stenosis had relapsed centrally but subsequently
      died of intercurrent disease. Two other patients died of intercurrent disease at
      26.2 and 41.9 months, respectively, without evidence of relapse. Nine other
      patients had been followed with no evidence of local relapse for 23.7 to 54.6
      months. CONCLUSION: This vaginal template implantation is satisfactory in
      treating cervical carcinoma patients with vaginal stenosis.

PMID- 9639724
TI  - [loop electrosurgical excision procedure: a review of our recent experience].
AB  - OBJECTIVE: To investigated whether persistence or recurrence of cervical
      intraepithelial neoplasis (CIN) is associated with an involved excisional margin
      during loop electrosurgical excision procedure (LEEP). METHODS: The records of
      256 consecutive LEEP were studied. After LEEP, all patients were followed up by
      colposcopy and cytology at 4 to 6 month intervals for at least two years. A
      patient was classified as having persistent disease if SIL was seen within one
      year of treatment or recurrent disease if SIL was detected after one year of
      treatment. All relevant patient details including cytology, colposcopy findings,
      treatment histology, complications, recurrence or persistence of disease entered
      into a computer database. RESULTS: Complications occurred in 8 patients (3.1%).
      LEEP was successful in treating 226 patients (95.4)%. Eleven patients (4.6%) had
      persistent SIL. Involvement of the resection margin was a significant risk factor
      for persistent disease (3.1% for uninvolved margins vs 11.4% for involved
      margins, P < 0.05). Similarly, recurrent disease occurred in 9.1% of patients
      with involved resection margins vs 2.1% with uninvolved margins (P < 0.05).
      Eleven patients (4.3%) had microinvasive carcinoma. Only 3 were identified by
      colposcopy and directed biopsy. CONCLUSION: LEEP is established as a safe and
      efficacious method for the treatment of CIN, long term morbidity including the
      effect on subsequent fertility must be observed.

PMID- 9639725
TI  - [Detection of human papillomavirus DNA in cervical squamous cell carcinoma in
      Xinjiang Uygur women].
AB  - OBJECTIVE: To study the association of cervical cancer with human papillomaviral
      (HPV) infection in Uygur women at high risk for development of cervical cancer in
      Xinjiang. METHODS: Cervical samples from 65 Uygur women with cervical cancer were
      collected. HPV DNA types 6/11, 16/18, 31/33/35 were studied by in-situ
      hybridization, and both consensus and type-specific primers for HPV types 6, 16
      and 18 were used in 58 cases by polymerase chain reaction (PCR). RESULTS: HPV DNA
      was detected in 43.1%, 22.4% and 77.6% of specimens by the in-situ hybridization,
      PCR using L1 consensus primers and E6 type-specific primers, respectively.
      CONCLUSIONS: E6 type-specific PCR was more sensitive than L1 consesus PCR and in
      situ hybridization detection of HPV DNA. These data supported the role of HPV DNA
      (particularly HPV 16) in the pathogenesis of cervical carcinoma in high risk
      women living in Xinjiang.

PMID- 9639726
TI  - [Analysis of the causes of neonatal deaths at term in pregnancy induced
      hypertension patients].
AB  - OBJECTIVE: To study the neonatal developmental status, its causes of death and
      their possible correlation in women complicated with pregnancy induced
      hypertension (PIH). METHODS: 46 autopsies of neonatal death at term with PIH and
      their clinical data were collected. The developmental status was evaluated by
      body weight, body length, and the weights of lungs, kidneys, liver and brain. The
      causes of death were reviewed by the clinicopathologic findings. RESULTS: The
      neonatal development features for mild PIH in term pregnancy approached to the
      normal levels of 37 to 38 gestation weeks. In the infants with moderate and
      severe PIH, the body weights, the weights of lungs and liver were significantly
      decreased in comparison with those of the mild PIH, respectively (P < 0.05),
      while the weights of kidneys and brain were not significantly decreased. The
      causes of death showed that pulmonary hypoplasia accounted for 23.9%, primary
      pulmonary atelectasis 10.9%, pulmonary hyaline membrane disease 21.7%, massive
      pulmonary hemorrhage 13.0%, the meconium aspiration 19.6% and others 10.9%. There
      was no difference in sex among the dead infants. CONCLUSIONS: The PIH syndrome
      had retarded the process of fetal growth and development, and associated with the
      severity of PIH, mostly involving the lung and the liver. The pulmonary
      hypoplasia and immaturity were the primary causes for neonatal death in PIH
      women.

PMID- 9639727
TI  - [Detecting pathogens of fetal defects in paraffin embedded tissues by polymerase
      chain reaction].
AB  - OBJECTIVE: To examine 3 types of pathogens in dead fetus with congenital defects
      for exploring the pathogenesis. METHODS: The paraffin embeded brain and liver
      tissues from 39 fetal autopsies with congenital defects were examined for
      toxoplasma, cytomegalovirus, and herpes simplex II by polymerase chain reaction.
      Among them 16 placentae were examined as well. RESULTS: Pathogens were detected
      in 25 of 39 cases, a positive rate of 64%. Nine out of the 13 fetuses with
      urogenital defects were positive for the shove pathogens, while 8 from the 12
      with neural tube defects were positive as well. CONCLUSION: Intrauterine
      infection was one of the important causes of birth defects. The characteristics
      of placenta morphologic changes were described, and the significance of placenta
      investigation in congenital malformation was emphasized.

PMID- 9639728
TI  - [The mechanisms of progesterone treatment on endometrial carcinoma].
AB  - OBJECTIVE: To study the mechanisms of the exogenic progestrerone treatment on
      endometrial carcinoma. METHODS: We observed the morphologic changes of the
      endometrial cancer cells treated by exogenic progesterone with light and
      electronic microscopy. RESULTS: The main changes of the tumor cell treated were
      well differentiation, increase in secretory activity and apoptosis of tumor
      cells. CONCLUSIONS: Progesterone may directly affect tumor cells, inhibit the
      growth of tumor cells and lead to well differentiation. Clinically with
      preoperative and postoperative progesterone therapy, it can decrease the
      peritoneum implantation and metastasis, and also decrease the recurrence after
      operation.

PMID- 9639729
TI  - [Estrogen and progesterone receptors in endometrial carcinoma].
AB  - OBJECTIVE: To study the relationship between estrogen receptor (ER) and
      progesterone receptor (PR) and the clinico-pathologic features in endometrial
      carcinoma. METHODS: ER and PR contents of fresh tumor tissues taken from 70 cases
      of primary endometrial carcinoma were measured by biochemical (DCC) method and 30
      paraffin-embedded archival specimens of the 70 cases also by immunohistochemical
      (IHC) method. RESULTS: Both ER and PR positive rates were 77.1% by DCC assay and
      83.3% by IHC method. Excellent correspondency of one method to the other was
      observed (ER 83.3%, PR 86.7%). And the IHC method displayed further the origin of
      the tissue examined. The ER and PR levels correlated negatively with the grades
      of tumor (P < 0.01). ER and PR positive rates in adenocarcinoma (including
      papillary adenocarcinoma) and adenoacanthoma were higher than those in the other
      histological types (ER, P < 0.01; PR, P < 0.005). There was a positive
      correlation between the ER levels and obesity. CONCLUSIONS: The levels of ER and
      PR and the histopathological classification and grading of the tumor tissue
      reflect biologic behaviors of endometrial carcinoma. ER and PR assays are
      important for endocrinotherapy and in predicting prognosis.

PMID- 9639730
TI  - [The effect of gestational impaired glucose tolerance on fetus and newborns].
AB  - OBJECTIVE: To study the effect of gestational impaired glucose tolerance (GIGT)
      on fetus and newborns. METHODS: 52 GIGT mothers and 34 gestational diabetes
      mothers (GDM) were subjected to systematic monitoring prospectively, other 44
      normal mothers served as controls. The perinatal outcomes were compared in the
      three groups. RESULTS: The incidence of macrosmia in the GIGT group was higher
      than that of the control group (P < 0.025). Neonatal blood glucose level in the
      GIGT group at 2 hours of age was the lowest in the three groups (P < 0.05). The
      incidence of hypoglycemia, polycythemia and wet lung in the GIGT group was higher
      than that of the control group. CONCLUSION: GIGT and GDM are important factors
      for poor perinatal outcome. Obstetricians and pediatricians must pay more
      attention to it.

PMID- 9639731
TI  - [Prenatal diagnosis of fetal nuchal cystic hygroma in 22 cases].
AB  - OBJECTIVE: To investigate the early diagnosis and prognosis of fetal nuchal
      cystic hygroma. METHODS: 72 cases of fetal nuchal cystic hygroma diagnosed in
      uterus were analyzed retrospectively. RESULTS: Most of the cases were diagnosed
      by B ultrasound between 15-26 gestational weeks. 55.9% the multipara had abnormal
      pregnant history, and 40% (4/10) of fetuses with karyotype performed had chrosome
      abnormality. Except for fetal deaths and induced abortions, 3 cases had term
      deliveries: one neonatal death, one was born with hygroma of 5.9 cm x 3.7 cm and
      transferred for surgery, and the other one with hygroma disappeared at the 37th
      week and baby was born at 40 week with normal appearance. CONCLUSIONS: This
      disease is one of common fetal morphological abnormalities. Few may recover
      spontaneously but most have poor outcomes.

PMID- 9639732
TI  - [Renin-angiotensin system: involvement in polycystic ovarian syndrome].
AB  - OBJECTIVE: To investigate the relationship between renin-angiotensin system (RAS)
      and polycystic ovarian syndrome (PCOS) METHODS: A pituitary-stimulating test with
      luteinizing hormone releasing hormone (LRH, 100 micrograms) was performed in two
      PCOS groups with similar mean testosteron (T) levels of luteinizing
      hormone/follicular stimulating hormone (LH/FSH) (LH/FSH > or = 3, group 1, n =
      15; LH/FSH < 3, group 2, n = 15) and the controls (n = 20) of matched body mass
      index with group 1. The basal level and LRH-evoked responses of LH, plasma renin
      activity (PRA), angiotensin II (AT II ) and aldosterone (ALD) were measured by
      RIA with commercially available kits. In the basal state, a positive correlation
      was found between T and AT II levels (r = 0. 49, P < 0.05) in all PCOS subjects.
      After LRH administration, susceptible individuals, especially of group 1 had
      exaggerated responses of LH, PRA, AT II and ALD as compared with the controls,
      and a positive correlation was also found between peak levels of LH and AT II (r
      = 0.54, P < 0.01). CONCLUSIONS: There is enhanced RAS function in PCOS especially
      in group 1. This may contribute to the excess androgen production and high
      incidence of ovarian hyperstimulation syndrome in this disorder.

PMID- 9639733
TI  - [Endometrial cytology in normal postmenopausal women and during hormone
      replacement therapy].
AB  - OBJECTIVE: To explore the possibility of endometrial cyopathologic examination as
      a method of monitoring endometrium during hormone replacement therapy (HRT) in
      postmenopausal women. METHODS: Endometrial cells were taken via tubal aspiration
      in 60 normal postmenopausal women (non-HRT group) and 41 with HRT for 3-18 months
      (HRT group). Their morphologic changes were observed and compared by
      cytopathologist. RESULTS: Atrophic endometrium was found in 51.7% of the non-HRT
      group. Its proportion increased with age and the time after menopause.
      Macrophages were seen in 68.3% of this group. However, in the HRT group the
      occurrence of atrophic type and macrophage (12.2%, 7.0% respectively) was
      significantly lower than that in the non HRT group (P < 0.05). Heterogeneity of
      endometrial cell type was shown both in non-HRT (38.3%) and HRT (65.8%) groups.
      CONCLUSIONS: Endometrial cells of postmenopausal women are not always atrophic in
      appearance. They change significantly during HRT. Endometrial cytological
      examination may be useful for monitoring during HRT.

PMID- 9639734
TI  - [Induction of apoptosis in human ovarian cancer cell line HO-8910 by transforming
      growth factor beta 1].
AB  - OBJECTIVE: To investigate the mechanism of inhibitory effects of Transforming
      Growth Factor beta 1 (TGF-beta 1) on human ovarian cancer cell in vitro. METHODS:
      The possibility of induction of apoptosis in human ovarian cancer cell line HO
      8910 cells after treatment with TGF-beta 1 was studied by using methods of DNA
      electrophoresis, P1-staining, TdT-mediated dUTP-x nick end labeling and flow
      cytometer assay (FCM); and the kinetic change of expression of c-myc was also
      studied by relative quantified RT-PCR. RESULTS: DNA-strand nicks were present in
      cells after treatment with TGF-beta 1 at the final concentration of 20 ng/ml for
      36 hours. The percent of labeled cells reached 75.55% on the time of 48 hours, PI
      staining-FCM assay also showed subdiploid peak of apoptotic cells at the same
      time. The typical apoptotic DNA ladder was present in genomic DNA preparation
      after treatment with TGF-beta 1 for 60 hours, meanwhile, the expression of c-myc
      in cells started to decrease beginning at treatment for 9 hours. CONCLUSIONS: TGF
      beta 1 can induce apoptosis in HO-8910; such an inductive effect may occur mainly
      in G0/G1 phase. The effects of TGF-beta 1 on the inhibited expression of c-myc
      and on the enhancement of cAMP concentration may also play important roles in the
      process of apoptotic induction.

PMID- 9639735
TI  - [Emphasizing clinical research on gynecological oncology].

PMID- 9639736
TI  - [Summary of 5th National Symposium on Gynecological Oncology].

PMID- 9639737
TI  - [Expression of glutathione S-transferase-pi in operative specimens as marker of
      chemoresistance in patients with ovarian cancer].
AB  - OBJECTIVE: To study the relationship between the expression of glutathione S
      transferase-pi (GST-pi) in operative specimens and chemoresistance in patients
      with ovarian cancer. METHODS: The expression of GST-pi in 87 epithelial ovarian
      cancer tissues and 30 normal ovarian epithelial tissues was determined with
      labelled streptavidin biotin method (LSAB). All the patients had not received
      chemotherapy before operation. We used Chi-Square and Cox-Mantel test to analyze
      the relativity between the expression of GST-pi and clinical pathological data,
      chemotherapeutic response, prognosis in patients with ovarian cancer. RESULTS:
      (1) 59 (67.8%) of 87 ovarian cancer tissue were demonstrated to be positive
      expression with GST-pi, but all 30 normal ovarian epithelial tissue were
      negative. (2) There was no direct correlation between the expression of GST-pi
      and clinical pathological data. (3) 43 (43/59) of GST-pi positive cases were
      chemoresistant, while only 3 (3/28) of GST-pi negative ones were chemoresistant.
      (4) The difference in the chemotherapeutic response between the two groups was
      obviously significant (P < 0.005). The survival period of the patients with GST
      pi positive expression was also obviously shorter than that of those with GST-pi
      negative expression (P = 0.004). CONCLUSION: These results strongly suggest that
      GST-pi expression in epithelial ovarian cancer tissues is closely related to
      chemoresistance clinically and it may be served as a useful marker to predict the
      prognosis of patients.

PMID- 9639738
TI  - [The relationship between multi-drug resistance gene expression and drug
      resistance of ovarian carcinoma].
AB  - OBJECTIVE: To study the relationship between multi-drug-resistance (MDR1) gene
      expression and the drug resistance of ovarian carcinoma and the reversing potency
      of drug-resistance modifying agent--cyclosporin A (CsA). METHODS: Tumor-bearing
      mice of ovarian carcinoma cell (OVCA3) were divided randomly into three groups:
      control group, adriamycin (ADM) group and ADM +CsA group. The tumor growth rate
      and the survival rate of mice were investigated and compared among the groups. 32
      frozen specimens of ovarian carcinoma tissue from patients were examined for the
      expression of MDR1 gene by means of RT-PCR. RESULT: Ovarian carcinoma cells with
      positive MDR1 gene expression showed cross drug-resistance to ADM, daunorubicin
      (DNR), vincristine (VCR) and etoposide (VP-16), the value of inhibiting
      concentration (IC50) is 4.1-15.5 times of that of the cells with negative MDR1
      gene expression. To tumor-bearing mice, there was significant difference in tumor
      growth rate between mice given combined therapy of CsA + ADM and those given ADM
      only (P<0.01) Of the 32 frozen specimens of ovarian carcinoma tissue, there was
      no confirmed relationship between MDR1 gene expression and the pathologic type or
      differential grade. The possibility of poor prognosis of patients with positive
      MDR1, gene expression was 16.07 (1.78-144.7) times of that of patients with
      negative MDR1 gene expression. CONCLUSION: MDR-related drug can induce the
      overexpression of MDR1 gene and result in the appearance of the multidrug
      resistance phenomenon. CsA can partially reverse the multidrug resistance of
      ovarian carcinoma cells both in vitro and in vivo. Detection of MDR1 gene
      expression in patients of ovarian carcinoma could be used as an index to predict
      the prognosis of the patients.

PMID- 9639739
TI  - [Effects of herpes simplex virus thymidine kinase gene transduction and prodrug
      on ovarian cancer cell].
AB  - OBJECTIVE: To evaluate the efficacy of gene therapy with the herpes simplex virus
      thymidine kinase (HSV-TK) gene transference followed by ganciclovir (GCV) therapy
      in ovarian cancer. METHODS: HSV-TK gene was inserted into the hind III site of
      pLNSX vector and recombinant plasmid (pLNS/HSV-TK) was constracted. Then, the
      recombinant plasmid was transfered into PA317 packaged cell and the producer cell
      line of recombinant retrovirus vector pLNS/HSV-TK was established. The
      cytotoxicity efficacy of HSV-TK/GCV system to AO cell line was evaluated by
      microcucture tetrajolium test (MTT) method. RESULTS: The recombinant retroviral
      vector pLNS/HSK-TK can transfer HSV-SK gene into the genome of AO cell line and
      make it sensitive to GCV. The growth inhibitory rate of AO cell line transfered
      by pLNS/HSV-TK was 98.0% in the medium containing 400 mumol GVC. CONCLUSION: The
      ovarian cancer cell line transfered by HSV-TK gene regressed rapidly in response
      to the GCV therapy.

PMID- 9639740
TI  - [Chemotherapy repeated injection via pelvic retroperitoneal cannulation].
AB  - OBJECTIVE: To investigate the feasibility of chemotherapy for lymphatic
      metastases of gynecologic cancer by repeated injection via pelvic retroperitoneal
      cannulation. METHODS: 5-fluorouracil (5-FU), thiotepa, methofrexate were
      repeatedly injected into the pelvic retroperitoneal space of 25 dogs and 24
      patients respectively via cannulation. Microscope and high-performance liquid
      chromatography were used to observe the drug concentration of 5-FU and pathologic
      changes of the involved tissues. RESULTS: Animal experiment showed no toxicity to
      vessels, ureter and the normal tissues involved; nodal 5-FU concentration of
      repeated injection side was 7 to 9 times of that on the peripheral connective
      tissue (P < 0.05). Clinical study revealed: (1) the external iliac, hypogastric,
      obturator, deep inguinal and most of the common iliac lymph nodes were submerged
      in the 5-FU solution; (2) pelvic and periaortic nodal 5-FU concentrations of
      repeated injection side were 20 to 73 and 27 to 110 times of that on single
      injection side respectively; nodal 5-FU concentration was 11 to 20 times of that
      on the peripheral connective tissue; (3) metastatic cancer cells of nodal in the
      study group showed obvious degeneration and necrosis while no changes in the
      control; (4) no severe complications or adverse effects were observed.
      CONCLUSION: Repeated injection via pelvic retroperitoneal cannulation was
      feasible and probably more effective for the treatment of lymphatic metastases of
      gynecologic cancer.

PMID- 9639741
TI  - [Treatment and prognostic factors of epithelial ovarian cancer].
AB  - OBJECTIVE: To study the treatment results and prognostic factors of epithelial
      ovarian carcinoma. METHODS: Retrospective study of 155 cases of ovarian
      epithelial carcinoma admitted in our hospital since Jan. 1970 to Dec. 1992. All
      of these cases had postoperative pathological diagnosis and staging according to
      FIGO. 42 cases had second operations and 4 cases had the third. 149 cases had
      postoperative chemotherapies except for 6. Chemotherapies were also given to 32
      cases after the second operation, while 9 for recurrence. RESULTS: The 2-year, 5
      year, 10-year survival rates of stage I were 92.4%, 87.0%, 70.6%; and II 91.9%,
      63.6% 47.8%; III 59.9%, 38.2%, 19.2% and IV 25.0%, 25.0%, 0.0% respectively. All
      6 cases without chemotherapy after surgery died within 2 years. The results
      indicated that the prognosis of ovarian epithelial carcinoma was related to
      clinical stage, cellular grade and tumor residues. The 5-year survival rates for
      stage I was 87.0% and III 38.2% (P < 0.001); and cell G1 95.0% and G3 11.8% (P <
      0.001), while no residual tumor 97.6% and with residual tumor > 2cm 21.2% (P <
      0.001) respectively. CONCLUSION: Residual tumor of ovarian epithelial carcinoma <
      2cm after primary surgery and chemotherapy right after surgery can improve
      survival rates.

PMID- 9639742
TI  - [Immunohistochemical locating and quantitative studies of 5-hydroxytryptamine and
      5-hydroxytryptamine receptor in placental villi of patients with pregnancy
      induced hypertension].
AB  - OBJECTIVE: To supply evidence of relationship between pregnancy induced
      hypertension (PIH) and 5-hydroxytryptamine (5-HT) and 5-hydroxytryptamine
      receptor (5-HTR) synthesized by placental villi. METHODS: Five normal placentas
      and 15 placentas of PIH were used for studying localization and quantification of
      5-HT and 5-HTR in placental villi by using immunohistochemical and in situ
      quantitative methods. RESULTS: Syncytiotrophoblasts and capillary endothelium in
      placental villi of control group showed 5-HT and 5-HTR positive immunoreaction,
      but in placental villi of group with PIH, syncytiotrophoblasts appeared 5-HT and
      5-HTR weak positive immunoreaction and capillary endothelium appeared 5-HT and 5
      HTR weak positive or negative immunoreaction. The results of in situ quantitation
      showed that the content of 5-HT and 5-HTR in placental villus
      syncytiotrophoblasts of group with PIH were significantly lower than those in the
      control group. CONCLUSIONS: The content of 5-HT and its receptor in placenta may
      be related to PIH.

PMID- 9639743
TI  - [Changes of concentrations of umbilical blood monoamines in low birth weight
      infant and their clinical significance].
AB  - OBJECTIVE: To investigate the changes of concentrations of umbilical blood
      monoamines in low birth weight (LBW) infants and their clinical significance.
      METHODS: By fluorescence spectrophotometry, the concentrations of umbilical
      plasma norepinephrine (NE), dopamine (DA), 5-hydroxytryptamine (5-HT) and 5
      hydroxyindoleacetic acid (5-HIAA) in 18 LBW before and after delivery were
      measured and compared with 20 normal birth weight (NBW) infants. RESULTS: The
      concentration of all monoamines, especially of the 2 catecholamines, i.e. NE and
      DA, were markedly lower in LBW than that in NBW (P < 0.05-0.01), regardless of
      prepartus or postpartus; the concentrations of all monoamines in postpartal
      umbilical plasma in both of LBW and NBW were higher than those in prepartal, and
      the increase of NE in NBW showed significant difference (P < 0.05). CONCLUSIONS:
      The decrease of all monoamines, especially of catecholamines in LBW could be one
      of the reasons causing the increase of mortality and the decrease of mental and
      physical development in LBW.

PMID- 9639744
TI  - [Insulin growth factor I in the development of ovarian follicles].
AB  - OBJECTIVE: To investigate the role of insulin growth in factor-1 (IGF-1) in the
      development of ovarian follicles under the stimulation of gonadotropins in an in
      vitro fertilization (IVF) program. METHODS: Radioimmuoasssy was used to determine
      the levels of sex hormones and IGF-1 in the serum and follicular fluid samples.
      In situ hybridyzation was used to detect the expression of IGF-1 and IGF-1
      receptor (IGF-1R) in the granulosa cell obtained from follicular aspiration in
      women undergoing IVF egg retrieval procedures. RESULTS: (1) Levels of plasma IGF
      1 increased with the development of follicles (P < 0.001); follicular fluid (FF)
      IGF-1 levels were lower than those of matched plasma; FF-IGF-1 decreased with
      increase of follicle numbers (P < 0.01), e.g. in patients with less than 2
      follicles (diameter > or = 15 mm) at the tine of ovum pick-up the FF-IGF-1 levels
      were much higher than patients with more than 2 follicles (P < 0.05). (2)
      Significant negative correlation was found between plasma IGF-1 and plasma E2 and
      also between FF-IGF-1 and FF-follicle-stimulating hormone (FSH) during ovum pick
      up (P < 0.01). (3) IGF-1 mRNA was not, while IGF-1R mRNA was found to be present
      in the human granulosa cells taken at ovum pick-up. CONCLUSIONS: Plasma IGF-1
      production might be stimulated by gonadotropins and distributed into the ovarian
      follicles by diffusion from peripheral circulation, acting upon the granulosa
      cells and therefore plays a complementary role with the gonadotropins in the
      regulation of follicular development.

PMID- 9639745
TI  - [Responses of growth hormone and prolactin to L-Dopa in women with polycystic
      ovarian syndrome].
AB  - OBJECTIVE: To evaluate the altered dopaminergic modulation of growth hormone (GH)
      and prolactin (PRL) in polycystic ovarian syndrome (PCOS). METHODS: Responses of
      GH and PRL to L-Dopa (L-DA) (500 mg) were observed in two PCOS groups (LH/FSH >
      or = 3, Group I, n = 15, LH/FSH < 3, Group II, n = 15) and the control (n = 20).
      RESULTS: Significantly lower GH (P < 0.01) and higher PRL levels (P < 0.05 in
      group I) in the basal state, and lower responses of GH and PRL to L-DA were found
      in two PCOS groups as compared with the control. CONCLUSION: The altered basal
      levels and blunted L-DA evoked responses of GH and PRL suggest a relative
      decrease of the dopaminergic activity in PCOS patients.

PMID- 9639747
TI  - [The risks and benefits of hormone replacement therapy in postmenopausal women].

PMID- 9639746
TI  - [Small cell carcinoma of the cervix].

PMID- 9639748
TI  - [Prevention and treatment of postmenopausal osteoporosis].

PMID- 9639749
TI  - [Summary of the National Symposium on Menopausal and Postmenopausal Problems].

PMID- 9639750
TI  - [The shrinkage of ovarian and uterine size and the decline of serum estradiol
      level in post-menopausal women].
AB  - OBJECTIVE: To investigate the shrinkage of ovarian and uterine size, and the
      decline of serum estradiol (E2) level in normal women. METHODS: Ovarian and
      uterine area of 92 perimenopausal and 292 postmenopausal women, measured by
      transvaginal ultrasonography, were analysed retrospectively and were compared
      with those of the controls consisting of 41 normal women in midfollicular phase,
      so did the serum E2 levels. RESULTS: As compared with the control group, ovarian
      area and endometrium thickness shrunk on an average of 30%, 2% and 56%, 48% in
      early perimenopausal and postmenopausal groups respectively. Serum E2 level and
      uterine area increased by 11% and 38% in early perimenopausal group, but
      decreased by 67% and 21% in postmenopausal groups respectively. No obviously
      further decline of serum E2 level was found 1 year after menopause, and of
      ovarian, uterine area 3-5 years after menopause. CONCLUSION: These data represent
      a normal profile of ovarian and uterine shrinkage and decline of serum E2 levels
      related to the time of menopause.

PMID- 9639751
TI  - [The effects of ethinyl estradiol on glucose metabolism in postmenopausal women].
AB  - OBJECTIVE: To study the effects of ethinyl estradiol on glucose metabolism in
      postmenopausal women. METHODS: Postmenopausal women were randomized as nine cases
      (group A) receiving 0.025 mg ethinyl estradiol (EE) and ten cases (group B)
      receiving EE 0.05 mg for three months. The oral glucose tolerance test (OGTT) and
      frequently sampled intravenous glucose tolerance test (FSIGT) were performed
      before and after EE respectively. The levels of plasma glucose, insulin were
      measured and the area under curve (AUC) and insulin sensitivity indexes (SI) were
      calculated. RESULTS: Both two dosages of EE administration effectively decreased
      the levels of fasting plasma glucose and insulin and significantly reduced the
      AUC of insulin. SI was increased significantly. There were no significant
      differences in AUC of glucose before and after treatment in group A, but in group
      B the AUC of glucose significantly increased after treatment. CONCLUSIONS: EE may
      significantly reduce the levels of fasting plasma glucose and insulin
      concentrations and abate the insulin resistance in postmenopausal women; 0.05 mg
      EE possibly causes the deterioration in glucose tolerance, suggesting the use of
      0.025 mg EE as an appropriate dosage.

PMID- 9639752
TI  - [Relative contribution of ageing and menopause to the changes of lumbar bone
      density in 1,400 Beijing women].
AB  - OBJECTIVE: To study the pattern of bone mass changes in women's lumbar spine and
      obtain evidence to guide the prevention of postmenopausal osteoporosis. METHOD:
      Bone mineral content (BMC) and bone mineral density (BMD) of lumbar 1-4 in 1 400
      Beijing women aged 20-85, were measured by dual energy X-ray absorptiometry.
      RESULTS: (1) Both BMC and BMD increased after age 20, reached the peak at the age
      of 30, and decreased significantly after the age of 50; (2) There was no
      significant change of BMC and BMD after the age of 25 in premenopausal women.
      Bone loss accelerated in the first 10 years after menopause. Women who
      experienced menopause early had lower bone mass. (3) The prevalence of
      osteoporosis in 1 121 postmenopausal women was 17.40%. CONCLUSION: Significant
      bone mass loss of lumbar spine occurs during the first decade following
      menopause, which is the key period for preventing osteoporosis.

PMID- 9639753
TI  - [Prevention of bone loss by chlorotrianisene in oophorectomized rats].
AB  - OBJECTIVE: To determine the influence of chlorotrianisene on bone metabolism in
      oophorectomized rats. METHODS: Forty-eight Wistar female rats, 70 days of age,
      were randomly divided into four groups: SV group (sham operation + vehicle), OV
      group (oophorectomy + vehicle), SE group (sham (operation + chlorotrianisene) and
      OE group (oophorectomy + chlorotrianisene). Chlorotrianisene or vehicle 4 ml/kg
      was given i.p. daily for 45 days from day 7 of being ovariectomized or sham
      operated. At the time of death, uterine weight was measured, and the thoracic
      vetebra 12, left tibia were collected and made into decalcified bone specimens
      for histomorphometry. RESULTS: There were significant difference in the uterine
      weight among each group. Significant different appearance by bone
      histomorphometry was seen between OV and the other three groups, but not shown
      between SV and SE, OE groups. CONCLUSION: These results suggest chlorotrianisene
      could inhibit bone loss and delay the atrophy of uterus induced by ovariectomy in
      Wistar female rats. It has protective effects on bone like other estrogen
      preparations.

PMID- 9639754
TI  - [Effects of progesterone on proliferation and differentiation of fetal rat
      calvarial osteoblasts in vitro].
AB  - OBJECTIVES: To investigate the influence of progesterone on proliferation and
      differentiation of osteoblast at the levels of gene expression and cell
      functions. METHODS: Fetal rat calvarial osteoblasts were cultured in vitro in the
      presence of (10(-9) mol/L-10(-6) mol/L) progesterone. Cell proliferation,
      alkaline phosphalase (ALP) activity, osteocalcin mRNA expression and osteocalcin
      secretion in the medium and bone nodule formation were analyzed. RESULTS:
      Progesterone did not influence cell proliferation; Progesterone enhanced the ALP
      activity in rat osteoblasts; Progesterone stimulated osteocalcin mRNA expression
      in a dose-dependent manner and increased the amount of osteocalcin in the culture
      medium; Progesterone increased both number and area of bone nodule formation.
      CONCLUSION: Progesterone has a multi-stimulating effect on the differentiation of
      fetal rat calvarial osteoblast, hut no effect on cell proliferation.

PMID- 9639755
TI  - [Relationship between human parvovirus B19 infection and spontaneous abortion].
AB  - OBJECTIVE: To determine whether there is a relationship between parvovirus B19
      infection and spontaneous abortion. METHODS: 105 embryo tissues from spontaneous
      abortions of unknown cause during 1994-1995 were studied using nested polymerase
      chain reaction (PCR) assay for parvovirus B19 DNA. As controls 40 fetal tissues
      were also examined. Among which, 20 were collected from induced abortions, and
      the others were stillbirths. The positive specimens underwent further study for
      TORCH infections. RESULTS: 26 (24.5%) were B19 DNA positive in the case group and
      2 (5.0%) in the control group. The difference was significant (P < 0.05). Among
      26 positive specimens, 5 had cytomegalovirus (CMV) infection as well as 2 had
      both CMV and herpes simplex virus (RSV) infections. CONCLUSIONS: Parvovirus B19
      infection may be an important pathogen for spontaneous abortion, and it is
      suggested to investigate parvovirus B19 infection among pregnant women in China.

PMID- 9639756
TI  - [Histomorphometric study of the effect of nylestriol on bone turnover in
      ovariectomized rabbits].
AB  - OBJECTIVE: To assess the effect of Nylestriol on postmenopausal osteoporosis in
      an attempt to reveal its mechanism. METHODS: Thirty-seven month-old female New
      Zealand white rabbits were randomized into 3 groups (10 rabbits per group):
      treatment group [ovariectomized (OVX) + nylestriol (2 mg, monthly)], OVX control
      group (OVX + vehicle) and normal control group (sham operation + vehicle). Six
      months later, all rabbits were subjected to tetracycline labelling and then were
      killed. Under VIDAS system, bone turnover was assessed by bone histomorphometry.
      RESULTS: Bone volume trabecular (BV/TV), relative osteoid volume (OV/BV),
      osteoblastic index (OBI) and bone formation rate at tissue level [BFR(T)]
      increased in treatment group compared with OVX control group and (or) sham
      control group. CONCLUSIONS: Nylestriol can increase the number of osteoblast,
      which resulted in more bone matrix production and consequently converted the bone
      turnover of OVX rabbits to a positive balance situation. It indicated that
      Nylestriol was probably a stimulator for osteoblast recruitment and (or)
      proliferation.

PMID- 9639757
TI  - [The clinical and pathological characteristics of epithelial ovarian carcinoma in
      patients with age under 40].
AB  - OBJECTIVE: To investigate the clinical and pathological characteristics of
      epithelial ovarian carcinoma in patients with age under 40. METHODS: From Jan
      1978 to Dec 1992, 54 cases with epithelial ovarian carcinoma under 40 years old
      were admitted to our hospital and enrolled in the study group, another 54
      patients suffered from the same disease with age over 40 in the same period were
      served as control. Comparison analysis for clinical and pathologic data of 2
      groups was performed using SPSS and SURVALC statistics software. RESULTS: Main
      complaint because of either pelvic mass or abdominal mass found by chance was
      more common in study group (46.3%) than that in control group (27.8%). whereas
      because of symptoms was less common in study group (53.7%) than in control group
      (72.2%). Other parameters such as early stage (I and II) rate (61.1%), unilateral
      tumor rate (68.5%), average maximum diameter of tumor (13.6 cm), highly
      differentiated rate (50%) and the possibility for tumor reductive surgery were
      higher in study group than in control group. The difference of histological
      pattern and chemotherapy between 2 groups was not significant. Single variate
      analysis showed that the prognosis was better in study group. The 2-year and 5
      year survival rates were 69.8% and 50.2% respectively. No recurrence was found in
      the 8 patients in whom the contralateral healthy ovary remained. However multiple
      variate analysis indicated that age was not a prognostic factor. CONCLUSION:
      Epithelial ovarian carcinoma was prone to be lower degree malignancy in patients
      under 40 years therefore the prognosis of them was better. It might be resonable
      to have healthy ovary left in some select cases.

PMID- 9639758
TI  - [Pregnancies complicated by human B19 parvovirus infection: prevention and
      treatment].

PMID- 9639759
TI  - [Pregnancy and hypertension].

PMID- 9639760
TI  - [Current status and trends of prenatal gene diagnosis].

PMID- 9639761
TI  - [Rapid prenatal diagnosis of Down's syndrome in the first trimester of pregnancy
      by fluorescence in situ hybridization].
AB  - OBJECTIVE: To assess whether fluorescence in situ hybridization (FISH) with
      chromosome 21, specific DNA probe is applicable as a prenatal diagnostic tool for
      Down's syndrome. METHOD: We used FISH with chromosome 21 specific probe on 30
      uncultured chorionic villi cell samples to detect the Down's fetus, and we also
      performed the conventional chromosome analysis of chorion cells from parallel
      samples. RESULTS: In samples with disomic karyotype, an average of 1 percent (0-5
      percent) of the nuclei had three hybridization signals. By contrast, in the
      samples of trisomy 21 fetus, an average of 86 percent (78-91 percent) of the
      nuclei displayed three signals. CONCLUSION: FISH can provide a rapid and accurate
      method for the first trimester prenatal diagnosis of Down's syndrome.

PMID- 9639762
TI  - [Prenatal screening for major fetal defects by using of maternal serum markers].
AB  - OBJECTIVE: To investigate the effect of second-trimester maternal serum markers
      AFP, beta-hCG, uE3, for prenatal screening of the fetal defects. METHODS: In 677
      women the triple markers were measured. Some factors that may affect the testing
      such as maternal weight, gestational age, were adjusted on analyzing the result
      of the testing. Each woman, who underwent the triple screening, will be followed
      up until her fetus was delivered. RESULTS: Among the women who were screened, 11
      patients who presented at least one marker positive were identified as having an
      abnormal fetus, and the positive rate was 1.6%. While 32 women were confirmed to
      be false positive with a rate of 4.7%. Another 11 women had fetal demise on
      second-trimester, which had been proved to be not caused by fetal abnormality.
      CONCLUSION: Maternal triple serum markers may take as a routine protocol for
      prenatal screening of the fetal defects.

PMID- 9639763
TI  - [The human SRY gene for prenatal diagnosis].
AB  - OBJECTIVE: To establish the method for prenatal sex diagnosis of the fetus
      carrying sex-linked genetic disorder. METHOD: Human SRY gene was amplified by
      polymerase chain reaction. A 422-bp male specific fragment was obtained. RESULTS:
      The fragment was identified in 10 men, but unidentified in 10 women. The
      diagnostic accordance rate of 20 amniotic fluid samples was 100%, 22 of 47
      chorionic villi samples were positive. The rate of positive/negative (22/25) was
      nearly the sex rate of newborn babies. In the meantime, direct-PCR amplification
      of blood and amniotic fluid was completed. The fragment was shown from 4
      microliters to 0.5 microliters of blood and from 2 ml to 0.5 ml of amniotic
      fluid. CONCLUSION: The results show that fetal sex determination by PCR will be
      suitable for clinical prenatal diagnosis of sex-linked genetic disorders.

PMID- 9639764
TI  - [AFP, uE3, beta-hCG levels applied for prenatal diagnosis of Down's syndrome].
AB  - OBJECTIVE: To investigate the relationship between fetal trisomy 21 and alpha
      fetoprotein (AFP), unconjugated oestriol (uE3) and beta human chorionic
      gonadotropin (beta-hCG) levels in maternal serum, amniotic fluid and fetal serum.
      METHOD: AFP, uE3 and beta-hCG levels in maternal serum, amniotic fluid and fetal
      serum from 17 pregnancies with fetal trisomy 21 and 131 unaffected control
      pregnancies were measured between 16 to 28 weeks gestation using
      radioimmunoassay. RESULTS: In these pregnancies with fetal trisomy 21, the AFP
      and uE3 levels in maternal serum, amniotic fluid and fetal serum were lower than
      those in controls; but beta-hCG levels were higher (P < 0.05). CONCLUSION: To
      measure maternal serum AFP, uE3 and beta-hCG levels will be useful in prenatal
      detection of trisomy 21.

PMID- 9639765
TI  - [Clinical observation on Doula delivery].
AB  - OBJECTIVE: To improve the obstetricare quality during labour and delivery, our
      hospital carried out Doula delivery which is an appropriate technology in
      promoting natural delivery reported by Dr M Klaus, USA. METHODS: Mothers were
      accompanied by senior experienced midwife who afforded continuous physical,
      psychological and emotional support during the whole course of labour. From April
      to August 1996, 46 cases of primigravida were selected as study group. Another
      336 primigravida given birth in the same period were taken as controls, who were
      accompanied by their family member during their active phase of labour. RESULTS:
      The results showed that the cesarean section rate was 6.5% in Doula group while
      20.8% in the control group. The difference was significant (P < 0.05). The
      duration of labour and volume of postpartum bleeding both declined obviously in
      the study group (P < 0. 05). CONCLUSION: Doula delivery offered better quality of
      health care during labour and decreased cesarean section rate duration of labour
      and postpartum bleeding.

PMID- 9639766
TI  - [Histochemical localization of nitric oxide synthase in the human placenta].
AB  - OBJECTIVES: To study localization, distribution and activity of nitric oxide
      synthase (NOS) in the human placenta and to speculate the action of nitric oxide
      (NO) during pregnancy. METHODS: NADPH-diaphorasc histochemical method was used to
      indicate the distribution, localization and activity of NOS in the placentae of
      normal term pregnancy (n = 21). Severe pregnancy induced hypertension (PIH) (n =
      15), intrauterine growth retardation (IUGR) (n = 2) and villi of early pregnancy
      (n = 16). RESULTS: The NOS reactive product called blue formazan was found in
      most of syncytiotrophoblast (STr) and located in top of cells in severe PIH and
      IUGR placentae. In normal term placentae the blue formazan was found in STr and
      located in base of cells. The number of blue formazan was more than that of PIH
      and IUGR placentae. Endothelial cells of most capillaries of the terminal villi
      in severe PIH and IUGR placentae were found to be deposited with blue formazan,
      but in normal term pregnancy, blue formazan was found only on rare occasion.
      CONCLUSION: Distribution and localization of NOS in placentae of normal term
      pregnancy, severe PIH and IUGR cases and early villi are specific. The NOS
      activity of STr in severe PIH placentae and IUGR placentae are lower than that of
      normal term placentae. The distribution and localization of NOS within the STr in
      severe PIH placentae and IUGR placentae are different from those in normal term
      placentae. The low activity of NOS secreted by placenta may be relative to the
      pathogenesis of PIH and IUGR.

PMID- 9639767
TI  - [Comparison of misoprostol and ricinus oil meal for cervical ripening and labor
      induction].
AB  - OBJECTIVE: To compare the safety and efficacy of intravaginal prostaglandin E1,
      misoprostol with ricinus oil meal for labor induction. METHODS: Sixty patients
      with an indication for induction of labor were randomly assigned to two groups
      (30 cases each) induction with misoprotol, 50 micrograms intra-vaginally every 3
      hours until active labor, or with that ricinus oil meal was taken. RESULTS: The
      time from start of induction to vaginal delivery was significantly shorter in the
      misoprostol group (12.2 vs 18.1, P < 0.05), and fewer patients in the misoprostol
      group required oxytocin augmentation (10.0% vs 40.0%, P < 0.05). The mean change
      in the Bishop score was significantly higher in those receiving misoprostol (5.5
      vs 3.1, P < 0.05). Uterine tachysystole occurred more frequently in patients in
      the misoprostol group (16.7%) than in the ricinus oil meal group (3.0%). No
      significant differences were noted in the mode of delivery and patients of
      successful labor induction. CONCLUSIONS: Vaginally administered misoprostol is an
      effective agent for the cervical ripening and induction of labor.

PMID- 9639768
TI  - [The value of blood sedimentation test in early diagnosis of amniotic fluid
      embolism].
AB  - OBJECTIVE: To explore the value of peripheral blood sedimentation in early
      diagnosis of amniotic fluid embolism. METHOD: The contents of amniotic fluid were
      detected with blood sedimentation test in 15 cases of amniotic fluid embolism and
      100 cases of normal pregnant women. RESULTS: The contents of amniotic fluid
      including particles of vernix caseasa, lanugo hair and epithelium cells were
      found in serum of amniotic fluid embolism cases but not found in cases of normal
      pregnant women. CONCLUSION: It suggested that the blood sedimentation test would
      be valuable for early diagnosis of amniotic fluid embolism.

PMID- 9639769
TI  - [The changes of T lymphocyte subsets and serum interleukin-2 receptor in
      peripheral blood of the pregnant women complicated by systemic lupus
      erythematosus].
AB  - OBJECTIVE: To determine the changes of T lymphocyte subsets, natural killer (NK)
      cell and serum interleukin-2 receptor (SIL-2R) in peripheral blood of the
      pregnant women with systemic lupus erythematosus (SLE). METHODS: T lymphocyte
      subsets NK cell, and SIL-2R in peripheral blood were detected by flow cytometry
      (FCM) and enzyme-labeled immunosorbent assay (ELISA) in 14 cases of pregnant
      women complicated by SLE (SLE+NP), 18 cases of stationary phase SLE (SLE), 20
      cases of normal non-pregnant women (NNP) and 20 cases of normal pregnant women
      (NP). RESULTS: The percentages of CD4+ cell were decreased significantly in
      SLE+NP group as compared with the other three groups (P < 0.01); and the ratio of
      CD4+/CD8+ was decreased significantly in SLE+NP group, as compared that in SLE
      group and in NNP group (P < 0.01). There were no difference in the number of NK
      cells among the four groups. The SIL-2R values were found to be increased
      significantly in the SLE+NP group, as compared with that of other three groups (P
      < 0.01). CONCLUSION: The observation on the changes of peripheral T lymphocyte
      subsets and SIL-2R may be helpful for monitoring progress of SLE during
      pregnancy.

PMID- 9639770
TI  - [Immunohistochemical study on the decidua vessels in recurrent spontaneous
      abortion].
AB  - OBJECTIVE: To investigate the effects of uterine local immunological factors in
      recurrent spontaneous abortion (RSA). METHODS: The decidua vessels were studied
      by immunohistochemical ABC method in 26 cases of RSA and 10 cases of normal
      pregnant women (control group). Meanwhile, serum IgG, IgM, IgA, C3 and CH50 were
      determined in RSA group and in control group. RESULTS: In RSA cases, the
      depositions of IgM (17 cases, 80.8%) were significantly increased (P < 0.001,
      respectively) as compared with the control group, the depositions of IgG (2
      cases, 7.8%) were significantly decreased (P < 0.001); the levels of serum C3,
      CH50 were significantly decreased (P < 0.01 respectively), but the level of serum
      IgA was increased significantly (P < 0.05) as compared with the control group.
      The depositions of C3 were significantly increased in RSA who had autoantibodies
      (P < 0.01), as compared with those without autoantibodies. In addition, the
      positive stain of IGM and C3 in the cytoplasm and nuclei of decidua cells and in
      the cytoplasm of gland cells of some RSA patients were also observed. CONCLUSION:
      The results suggest that the immunological damage of decidua vessels is a very
      important factor in immunopathogenesis for RSA. Decidua cells and gland cells may
      have potential immunological function.

PMID- 9639771
TI  - [Carcinoma metastatic to the cervix: a study of 19 cases].
AB  - OBJECTIVES: To report the clinical features and to evaluate the treatment results
      of 19 cases of cervical metastatic carcinoma. METHODS: We analyzed
      retrospectively the 19 patients with carcinoma metastatic to the cervix treated
      during the period of 1959 to 1994 at Cancer Hospital, Chinese Academy of Medical
      Sciences. RESULTS: The average age of patients was 43.7. The main symptom was
      irregular vaginal discharge and (or) bleeding. In most patients, the primary
      cancers originated from digestive tract or ovary. The treatment methods included
      radiotherapy alone, radiotherapy combined with chemotherapy after operation, and
      surgery plus radiotherapy. The 1-, 2- and 5-years survival rates (life-time table
      were 68.5%, 47.3% and 26.2% respectively, and the longest period for survived
      patient with dysgerminoma has lived was more than 22 years. CONCLUSION: The
      active proper treatment of primary cancer can prolong the survival time of
      patients with carcinoma metastatic to the cervix. The patients whose metastatic
      lesions are limited to the cervix and sensitive to the radiation may be cured by
      radiotherapy and combination therapy.

PMID- 9639772
TI  - [Prenatal screening for Down's syndrome].

PMID- 9639773
TI  - [Gene diagnosis of fragile X syndrome].

PMID- 9639774
TI  - Effect of dexamethasone on Glu-IR and GABA-IR neurons of hippocampus in rats.
AB  - Dexamethasone (Dex) was injected into the rat lateral ventricle and the changes
      of glutamate-immunoreactivity (Glu-IR) and gamma-aminobulyric acid
      immunoreactivity (GABA-IR) neurons in the hippocampus were immunocytochemically
      examined 2 h after injection. The results showed that Glu-IR neurons increased
      and GABA-IR neurons did not show marked change. The mechanism remains to be
      further studied.

PMID- 9639775
TI  - Mechanism of anti-beta-adrenoceptor antibody mediated myocardial damage in
      dilated cardiomyopathy.
AB  - Antibodies against beta(1)-adrenoceptor can be detected in serum of patients with
      dilated cardiomyopathy (DCM), which have beta-agonist-like activity, and induce a
      positive chronotropic effect on cardiac myocytes by its persistence at full
      strength. Effects of the antibodies against beta-adrenoceptor from sera of
      patients with DCM on myocardial cytotoxicity and cytoplasmic free Ca(2+)
      concentration ([Ca2+]i) were observed in the cultured single layer SD rat
      ventricular cells by using the cytotoxicity assay and fluorescent Ca(2+)
      indicator fura-2/AM. The positive sera of the anti-beta-adrenoceptor antibodies
      from patients with DCM markedly enhanced myocardial [Ca2+]i. Betaloc, a beta(1)
      receptor blocker, might inhibit the increase of the antibody-mediated myocardial
      [Ca2+]i, and the sera from healthy donors had no effect on myocardial [Ca2+]i.
      Our results suggest that the anti-beta-adrenoceptor antibody might increase
      myocardial [Ca2+]i and result in myocardial damage. The antibodies might activate
      receptor-gating Ca(2+)-channel, thereby causing myocardial [Ca2+]i rise and
      calcium overload. Early use of betaloc is recommended in the treatment of dilated
      cardiomyopathy.

PMID- 9639776
TI  - Effects of ligustrazine on bone marrow microvessel system in the early period of
      acute radiation injury in mice.
AB  - Sublethally irradiated mice were immediately treated with 250 mg/kg Ligustrazine
      Phosphiatis intraperitoneally twice a day for seven days, and the bone marrow
      microvessels of the Ligustrazine group was much greater than that of the control
      group. On the 7th day, the amount of the control group decreased to normal, while
      the ligustrazine group was still increasing, and the microvessel area was
      enlarged obviously.. The percentage of the hematopoietic tissue volume in bone
      marrow between the two groups had no significant difference in the first 7 days.
      On the 7th day after irradiation, the peripheral neutrophilic granulocytes
      increased in the Ligustrazine group. The results suggested that early use of
      Ligustrazine after acute radiation injury might improve the blood supply of bone
      marrow, and be helpful for recovery of hematopoiesis.

PMID- 9639777
TI  - Effect of concurrent use of rh-IL-3 and rh-GM-CSF on apoptosis of HL-60 cells
      induced by Ara-C.
AB  - The myeloid leukemic cell line HL-60 was studied by using DNA gel
      electrophoresis, flow cytomery, McAb C-myc, McAb Bcl-2 and CFU-L. From zero to 36
      h, the apoptosis rates of 8 different phases and other indexes were observed. The
      results showed that with the prolonged time of drug incubation, apoptosis of HL
      60 cells increased progressively. This effect can be enhanced obviously by rh-IL
      3 and rh-GM-CSF. At the same time, the killed rate of leukemic cells by Ara-C
      induction was increased. C-myc expression was decreased and Bcl-2 expression did
      not display apparent change. Interestingly, the normal hemopoietic cells were not
      affected by these two kinds of cytokine. The theoretical basis was provided for
      concurrent use of rh-IL-3, rh-GM-CSF and cytotoxic drugs whose purpose is to
      elevate remission rate during the phase of induced remission of leukemia.

PMID- 9639779
TI  - Redistribution of platelet membrane glycoprotein IV and release of intracellular
      alpha-granule thrombospondin in patients with chronic myelogenous leukemia.
AB  - The redistribution of platelet membrane glycoprotein IV (GPIV) and the release of
      intracellular alpha-granule thrombospondin (TSP) were examined and the inhibition
      of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) in patients with
      chronic myelogenous leukemia (CML) was observed and quantitation of beta-TG and
      PF4 in sera was conducted. GPIV in inactive platelet from CML was 36080 +/- 17010
      molecules/platelet as compared with 13190 +/- 4810 from the controls (P < 0.01).
      No abnormality was found in the distribution of platelet membrane GPIb and
      GPIIb/IIIa (P > 0.05). The GPIV redistribution on active platelet membrane
      induced thrombin (IU/ml) from CML and healthy donors was 44320 +/- 32310 and
      22800 +/- 12700 molecules/platelet respectively (P < 0.01). The difference in the
      release of intracellular alpha-granule TSP between CML and the control group was
      not found (P > 0.05). There was no direct correlation between GPIV expression and
      TSP binding after platelet activation. The high levels of beta-TG and PF4 in sera
      inhibited release of intracellular alpha-granule TSP in vitro. These results
      indicate that the abnormality of platelet membrane GPIV is a common marker in
      CML, therefore the specific increase of platelet GPIV in patients with CML may be
      a useful tool for the diagnosis and monitoring of the platelet dysfunction. The
      release of internal TSP pools is hindered by either beta-TG or PF4 in sera.

PMID- 9639778
TI  - Study on immunoregulation by interleukin-1 receptor antagonist in NZB/W F mice.
AB  - The immunoregulating effect of Interleukin-1-receptor antagonist (IL-1ra) in
      lupus-like NZB/W F1 mice was investigated to find possible approach to prevent
      lupus nephritis. 12 female NZB/W F1 mice of 13 weeks were randomly divided into 2
      groups. Each mouse in the treated group was intraperitoneally injected with IL
      1ra once every 2 weeks for 3 times at the dosage of 100 micrograms each time,
      while the control group was given injection of 0.1 ml normal saline. All the mice
      were killed at the age of 9 months and the immunologic function was examined.
      Results showed that this dosage could not completely prevent the development of
      lupus nephritis, but the renal damage was alleviated and the urine protein was
      decreased. Moreover, it could improve the immunofunction by significantly
      reducing the levels of serum IL-1 and obviously increase the activities of NK
      cells and IL-2 induced by ConA in mononuclear cells of spleen. There was no
      significant difference in the levels of serum IL-6 and TNF-alpha between the
      treated group and control group. It is concluded that IL-1ra has certain
      regulatory effect on the immunologic function of lupus-like NZB/W F1 mice.

PMID- 9639780
TI  - Nitric oxide synthase activity in arterial tissues of cirrhotic rats.
AB  - The changes in the activities of constitutive nitric oxide (NO) synthase (cNOS)
      and inducible NOS (iNOS) were investigated in arterial tissues of CCl4-induced
      cirrhotic adult SD rats. The aortic tissue homogenate were prepared in normal and
      cirrhotic rats. NOS activity was measured by conversion of 3H-arginine to 3 H
      citrulline. The activities of cNOS and iNOS were calculated in terms of presence
      or absence of Ca2+. The results showed that activities of total NOS, cNOS and
      iNOS in arterial tissues were all increased significantly in cirrhotic rats as
      compared with those in normal controls. There was a significant positive
      correlation between the activities of total NOS and cGMP content in cirrhotic
      arterial tissues.

PMID- 9639781
TI  - Expression of matrix metalloproteinase-9 mRNA in osteoporotic bone tissues.
AB  - Matrix metalloproteinases (MMPs), a sort of important enzymes involved in
      extracellular matrix metabolism, play critical roles in the process of tissues
      remodeling, wound healing and metastasis of tumors. Dot blot and in situ
      hybridization were used in this study to detect the expression and localization
      of MMP-9, an important proteolytic enzyme implicated in bone resorption in bone
      tissues. The results showed that the level of MMP-9 mRNA expression in
      osteoporotic bone tissues was significantly higher than that in normal control
      group and the cell types that expressed MMP-9 mRNA included mono- and multi
      nuclear osteoclasts and some lining cells on the surface of bone matrix. It was
      suggested that MMP-9 play a key role in the development of bone loss in
      osteoporosis.

PMID- 9639782
TI  - Bipolar esophageal electrocardiography by using standard limb leads.
AB  - The ear-xiphisternum distance (EXD, the distance from the low edge of the ear to
      the xiphisternal basis in supine position) was used as a reference value for
      esophageal catheter insertion. ECGs recorded in the esophagus with bipolar
      electrocardiography using standard limb lead (ESLL) and conventional unipolar
      lead (ECUL) were compared. 112 patients with sinus rhythm and 76 patients during
      paroxysmal supraventricular tachycardia (PSVT) whose P-wave and QRS complex did
      not overlap were studied. The results suggested that in sinus rhythm the
      amplitude of the P-wave in ESLL was larger and the T-wave was smaller than in
      ECUL. During PSVT, the P-wave was much clear and higher in each lead of ESLL than
      that in ECUL. The ideal range of esophageal ECG recording was situated between
      the end of EXD and 6.5 cm proximal to it.

PMID- 9639783
TI  - Experimental study on the effects of aprotinin on myocardial ischemia and
      reperfusion.
AB  - Direct effects of a high-dose aprotinin on the normally perfused hearts and the
      myocardial protection after ischemia and reperfusion were investigated in an
      isolated working rat heart model. In trial I, hearts had no ischemia and were
      perfused with either K-H solution or the K-H solution containing aprotinin (200
      KIU/ml) for 55 min. No statistically significant difference was observed in
      hemodynamics between the two groups. In trial II, hearts were exposed to 150 min
      period of global ischemia at 15 degrees C with 4 degrees C multidose St. Thomas'
      II solution (STS). The control group I received normal K-H solution; the group II
      was treated with the solution with aprotinin added. The group III was similar to
      the group I and received the STS enriched with aprotinin. On reperfusion, the
      recovery of hearts in group III was significantly better than those of the group
      I and II, as reflected by better hemodynamics and myocardial ATP levels and
      milder myocardial ultrastructural injury. There was no difference between the
      group I and II. These results suggest that the aprotinin a dose of 200 KIU/ml has
      no harmful effects on normally perfused hearts and has a marked myocardial
      protective effect on the prolonged myocardial ischemia when used in cold
      crystalloid cardioplegia.

PMID- 9639784
TI  - Effect of intra-arachnoid space perfusion on thromboxane A and prostacycline in
      experimental spinal cord injury.
AB  - In order to understand the relation between TXA2-PGI2 and secondary trauma and
      the effect of intra-arachnoid perfusion of dexamethasone and verapamil on
      alteration of TXA2-PGI2 following spinal cord injury, TXB2 and 6-keto-PGF alpha
      concentration and pathological changes in injured site 1, 2, 4, and 6 h after
      injury were studied using a rabbit spinal cord injury model by Allen's weight
      drop method.

PMID- 9639785
TI  - Role of injury of gastric parietal vessels by immunocomplexes in the mechanism of
      gastric mucosal lesion in portal hypertension with cirrhosis.
AB  - The present experiment employed the immunohistochemical technique and
      morphological observation to investigate the expression and distribution of C3,
      C4, IgG, IgE 5-HT in portal hypertensive pigs with pathological change of gastric
      mucosa and gastric parietal vessels. The wall of gastric mucosal mirco-vessels in
      portal hypertensive pigs had a positive or strong positive reaction of C3, C4,
      IgG, IgE and 5-HT with obvious injury of gastric mucosa normal pigs imparted
      negative or feeble positive reaction, suggesting that during portal hypertension,
      the gastric mucosal micro-vessels has deposit of immunocomplexes resulting in the
      injury of the micro-vessels. It might be a factor involved in the pathogenesis of
      the gastric mucosal lesion during portal hypertension with cirrhosis.

PMID- 9639786
TI  - Application of color Doppler ultrasonic examination in deep vein valvular
      incompetence in lower limbs.
AB  - By use of color Doppler Flow Imaging (CDFI), the morphologic and hemodynamic
      parameters such as the diameters of femoral and popliteal veins, blood flow
      velocity and the reflux of valve area were examined in lower extremity deep
      valvular incompetence (DVI) and normal control groups. The purpose was to
      evaluate the value of CDFI in the diagnosis of DVI. The results demonstrated that
      the parameters between the two groups had a very significant difference (P <
      0.001), indicating that the CDFI is non-invasive, cost-effective and safe and it
      might serve as a practical tool in the diagnosis of lower extremity deep valvular
      incompetence.

PMID- 9639787
TI  - Multiple respiratory gas monitoring causes changes of inspired oxygen
      concentration in closed anesthesia system.
AB  - Effect of multiple respiratory gas monitoring (MRGM) on inspired concentration of
      oxygen in circuit system during closed anesthesia was studied in 51 adult
      patients scheduled for abdominal surgery. Required flow rate of fresh oxygen
      (OFR), inspired oxygen concentration (FiO2) and oxygen saturation of pulse
      oximeter (SpO2) were measured continuously. Patients were equally divided into
      three groups at random, group C (no MRGN used), group M1 (using MRGM with its
      tail gas returned to circuit system), group M2 (using MRGM without tail gas
      returned). The results revealed that during 180 min of closed anesthesia, OFR
      required in group C and M1 were about 200-230 ml/min, and in group M2 it was
      about 400 ml/min. In group C FiO2 decreased by about 10% after 60 min of closed
      anesthesia (P < 0.01, 60 min vs 0 min) and then stayed stable at this level. In
      group M1, FiO2 decreased by 16% at 60 min and 34% at 180 min and the decrease was
      significantly greater than that in group C (P < 0.01). In group M2, FiO2 remained
      constant during closed anesthesia, which was much higher than those in group C
      and M1. The tail gas of Capnomac Ultima MRGM contained less oxygen than its
      sample gas drawn from circuit system simultaneously.

PMID- 9639788
TI  - Innervation of cholinergic vestibular efferent system in vestibular periphery of
      rats.
AB  - The innervation of cholinergic efferent fibers in the vestibular endorgans of the
      rats was investigated using a modified preembedding immunostaining technique of
      immunoelectron microscopy. A monoclonal antibody to choline acetyltransferase
      (ChAT) was used as a marker of cholinergic fibers. It was found that there were
      four types of cholinergic innervation in the vestibular endorgans of the rat: (1)
      cholinergic nerve endings formed axo-dendritic synapses with afferent chalice
      surrounding the type I sensory hair cells; (2) cholinergic nerve endings formed
      axo-somatic synapses with type II hair cells; (3) cholinergic fibers synapse with
      afferent nerve fibers and (4) a synaptic contact developed between cholinergic
      nerve endings. The results demonstrated that a multiform innervation of the
      cholinergic efferents exists in the rats vestibular periphery.

PMID- 9639789
TI  - Development and application of an instrument for analysis of bone structure on
      radiographs.
AB  - An instrument used for quantitative assessment of trabecular structure of radius
      on radiograph including trabecular number and trabecular width was developed
      using a microdensitometer and a single-chip microcomputer. The device is
      characterized by its high sensitivity, good reproducibility, convenience and
      economy. The results obtained with the instrument were significantly correlated
      to actual bone mineral content. This device can be used for the diagnosis of
      osteoporosis, fluorosis, rickets and bone damages caused by cadmium.

PMID- 9639790
TI  - Regulation of ApoE gene expression in mouse peritoneal macrophages by VLDL.
AB  - Mouse peritoneal macrophages (MPM) were incubated with ApoE-poor VLDL or ApoE
      rich VLDL at same concentrations for 24 h. The ApoE mRNA content increased in
      both groups than that in control and the highest ApoE mRNA content was seen in
      MPM incubated with ApoE-poor VLDL. The results suggest that VLDL could stimulate
      ApoE gene expression in MPM and the ApoE-poor VLDL has more pronounced effect. We
      think that the ApoE secreted by MPM may be incorporated into VLDL, especially the
      ApoE-poor VLDL, and thereby enhance the uptake of those lipoproteins by MPM or
      other local cells via ApoE-mediated receptor pathways.

PMID- 9639791
TI  - Relationship between invasiveness of pituitary somatotrophinomas and structural
      abnormalities of protein kinase C gene in human.
AB  - The potential role of the protein kinase C (PKC) transduction system in
      controlling proliferation of human pituitary somatotrophinomas was investigated.
      Twenty somatotrophinomas were studied using PCR and direct sequencing methods. No
      point mutation within the alpha PKC gene, previously thought to be associated
      with invasive pituitary tumors, was found in any of the 20 somatotrophinomas. It
      is concluded that PKC transduction system may play an important role in
      controlling pituitary somatotrophinoma proliferation, but there is no correlation
      between invasiveness and the previously reported alpha PKC gene mutation.

PMID- 9639792
TI  - Induction of osteocalcin gene expression in vitro by progesterone.
AB  - The effect of progesterone on osteocalcin gene expression was investigated in
      order to understand how progesterone acts on osteoblast in vitro. For this
      purpose, fetal rat calvarial osteoblasts were cultured in the medium containing
      10(-9) M-10(-6) M progesterone respectively for two weeks while the cells
      progressing differentiation. Northern blot analysis showed that progesterone
      increased the level of osteocalcin mRNA in a dose-dependent manner. Among those
      doses of progesterone employed in this study, only 10(-6) M hormone caused a
      significant induction of osteocalcin gene expression (2.3 fold, P < 0.01). Our
      results demonstrated for the first time that the osteocalcin gene expression is
      regulated by progesterone. In addition, the results obtained from our study
      provides a good evidence for the direct effect of progesterone on osteoblast in
      vitro.

PMID- 9639793
TI  - Abnormal change of p53 gene in gastric and precancerous lesions and APC gene
      deletion in gastric carcinoma and near tissues.
AB  - p53 gene mutation (exon4, 5, 6, 7, 8 and intron6) in gastric cancer and
      precancerous lesions and p53 gene (exon4 and ontron6), APC gene deletion in
      gastric carcinomas were studied by PCR/SSCP and PCR/RFLP. Results showed mutation
      rate of p53 in metaplasia, dysplasia and gastric carcinoma was 37.5% (3/8),
      42.17% (8/19), 53.33 (16/30) respectively. There was significant difference among
      groups of metaplasia, dysplasia, cancer and normal controls. No exon8 mutation
      was found in metaplasia and dysplasia, but 4 cases were found to have exon8
      mutation in cancer group. It is suggested that exon8 mutation occurs at the late
      stage of gastric cancer, but exon 5, 6, 7 mutation occur in the course of
      precancerous lesion to cancer. Loss of heterozygosity (LOH) of exon4, intron6,
      APC was 47, 37% (9/19), 8.73% (2/23), 16.67% (3/18) respectively. LOH of exon4
      had something to do with poor differentiation, lymph node metastasis, depth of
      invasion. LOH of exon4 may be of prognostic marker of gastric cancer. We are led
      to conclude that p53 gene mutation is an early event and perhaps work together
      with ras oncogene in gastric carcinogenesis.

PMID- 9639794
TI  - The molecular epidemiological study on enteric adenovirus in stool specimens
      collected from Wuhan area by using digoxigenin labeled DNA probes.
AB  - A summer-autumn (1994) molecular epidemiological study of enteric adenoviruses
      (EAds) in stool specimens collected in Wuhan area was conducted by using
      Digoxigenin-labelled DNA probes specific to EAd40 and EAd41 respectively. 44 of
      602 specimens were positive, among which 23 cases were identified as EAd40, 14
      were EAd41 infection and 7 were dual infection. The ratio of males to females for
      the positive specimens was 1. 44. The infection rate of EAd40 and EAd41 each
      displayed no marked difference in seasons (summer and autumn) and similar age
      distribution was found between them. All of the two types of EAds infections
      predominated in patients with diarrhea under 3 years old. The results indicated
      that the Digoxigenin probe could detect DNA quantities as low as 1 pg with
      satisfactory specificity and the technique can be used for both clinical and
      experimental purposes.

PMID- 9639795
TI  - Preliminary studies on the relationship between autoantibodies to heat stress
      proteins and heat injury of pilots during acute heat stress.
AB  - Comparison in the heart rate, oral temperature and lymphocyte DNA damage during
      heat stress was made in pilots with negative antibodies to heat stress proteins
      (HSPs) and those with positive antibodies in the man-made climate room with
      Western blot and comet assay. Our results showed that the increase in oral
      temperature, heart rate and lymphocyte DNA damage in pilots with the positive
      antibodies to HSPs were higher than those in pilots with the negative antibodies
      during heat stress. These results indicated that the presence of autoantibodies
      in plasma of pilots might reflect heat damage and high sensitivity to heat.

PMID- 9639796
TI  - The study on the relationship between the expression of calponin and gallstone
      formation.
AB  - In order to understand the molecular mechanisms of gallstone formation, the
      expression of calponin in animal model of gallstone disease was studied. High
      cholesterol diet was given to the guinea pigs to induce gallstone formation. RT
      PCR and Western-blotting were used to evaluate expression level of calponin gene.
      Down-regulation of calponin gene expression was observed in animals with
      gallstone, while myosin expression was relatively stable. Our results indicated
      that the decrease of calponin could increase the pressure of Oddi's sphincter,
      aggravate the stasis of bile and promote the gallstone formation.

PMID- 9639797
TI  - The effect of levobunolol hydrochloride on the calcium and potassium channels in
      isolated ventricular myocytes of guinea pig.
AB  - The effects of levobunolol hydrochlorid (Bun) on the type L calcium channel
      currents (ICA) and delayed rectifier potassium channel currents (IK) in isolated
      ventricular myocytes of guinea pig were studied by using patch clamp whole cell
      recording techniques. The results were showed that: 1) Bun caused a dose
      dependent decrease in ICA and a dose-dependent increase in IK of the ventricular
      myocytes. The threshold concentrations of Bun for ICA and IK were 10(-8) mol/L
      and 10(-7) mol/L respectively. The maximum effective concentration of Bun for bot
      ICA and IK was 3x10(-5) mol/L, and half-maximal concentration was 3x10(-6) mol/L;
      2) IK was blocked by 2x100(-6) mol/L tetraethylammonium (TEA). A concentration of
      3x10(-6) mol/L Bun showed a decreasing effect on the ICA as revealed by the
      current-voltage relationship curve, i.e., Bun caused an elevation of the curve;3)
      When ICA was blocked by 2x10(-6) mol/L Isoptin (Verapamil), at a concentration of
      3x10(-6) mol/L Bun showed an increasing effect on IK and the effect could be
      blocked by TEA. The above-mentioned results indicated that Bun had an inhibitory
      effect on ICA and a fascilitatory effect on IK. The results suggested that the
      molecular mechanisms of antihypertensive, heart rate slowing the beta -receptor
      blocking effects of Bun might be due to decrease of ICA and increase of IK.

PMID- 9639798
TI  - An experimental comparative study on the characteristics of ventricular
      fibrillation during cardiac arrest and methoxamine administration.
AB  - The effect of a pure alpha-adrenergic agent, methoxamine on ventricular
      fibrillation (VF) amplitude and the relation between hemodynamic parameters and
      survival in a rodent cardiopulmonary resuscitation (CPR) model were studied. Our
      results suggested that: 1) VF amplitude decreased during untreated VF, but it
      increased during pericardial chest compression: 2) methoxamine significantly
      increased the mean aortic pressure (MAP) and coronary perfusion pressure (CPP)
      but not VF amplitude, and the survival also increased due to elevation of CPP;
      and 3) all surviving animals with successful defibrillation had a higher VF
      amplitude.

PMID- 9639799
TI  - Effect of left ventricular outflow on flow convergence region on the left septal
      surface in ventricular septal defect.
AB  - The corrected shunt flow rate (Fc) and corrected defect orifice area (Ac) were
      calculated by modified equation F = 2 pi R2 (NL-VLVOT x Sin theta) in 23 patients
      with single membranous ventricular septal defect, in order to correct the effect
      of left ventricular outflow on flow convergence region on the left septal
      surface. The results indicated that Fc was closely correlated with Qp-Qs, and
      Qp/Qs measured by pulsed wave Doppler (r = 0.95 and r = 0.81 respectively, P <
      0.001). And the correlation between Ac and the diameter of defect (Dd) measured
      directly in two-dimensional views was better than that between uncorrected defect
      orifice area (A) and the Dd (r = 0.98 and 0.69, respectively, P < 0.001). The
      shunt flow rate calculated by ideal equation F = 2 pi R2 x NL overestimated the
      actual shunt flow rate in ventricular septal defect, especially in membranous
      type. Our study concluded that Fc can be used for a more accurate evaluation of
      the shunt severity of ventricular septal defect.

PMID- 9639800
TI  - A model of subarachnoid cavity drugs perfusion and its clinical application in
      treatment of spinal cord injury.
AB  - An animal model of subarachnoid cavity drugs perfusion and its prelimilary
      clinical application in treatment of acute spinal cord injury (SCI) were
      reported. Analysis of the heart rate (HR), ECG blood pressure (CVP, CAP)
      cerebrospinal fluid (CSF) pressuer and CSF gas and pH values of 10 healthy adult
      goats during subarachnoid daxamethasone verapamil perfusion showed that this
      model was safe anti reliable. 26 patients with acute SCI were selected for a
      clinical obseration. Good results were obtained in 7 cases who received this
      treatment of subarachnoid cavity perfusion with dexamethasone and verapamil.

PMID- 9639801
TI  - Sonographic diagnosis of bone tumors.
AB  - This paper presents the results of sonographic and radiographic examinations in
      48 patients clinically diagnosed as having bone tumors. Sonography revealed bone
      destruction in all 48 cases, elevated periosteum in 26 cases and soft tissue mass
      in 34 cases. The results obtained in this series demonstrate that most bone
      tumors have their characteristic sonographic features such as giant cell tumors,
      malignant bone tumors, bone cysts, as well as metastatic lesions. Study showed
      that sonography has equally high accuracy in the diagnosis of these tumors
      compared with radiography.

PMID- 9639802
TI  - Color Doppler monitoring of changes of utero-placental-fetal circulation in
      normal pregnancy and intrauterine growth retardation.
AB  - The utero-placental-fetal circulation (UPFC) of 150 subjects during second and
      third trimester was examined by using color Doppler. Of them 89 were normal woman
      and 58 were patients with intrauterine growth retardation IUGR). Our results
      showed that UPFC was increased gradually during normal pregnant period. In IUGR
      patients it was revealed that TAV and Q of UmA, UmV and UtA decreased at 20th
      week of gestation, especially after 30th week. PI, RI and S/D ratio of UmA were
      increased, but TAV, Q of UmA and UmV were markly reduced, so was UtA. PI were
      increased, but the changes of RI, S/D ratio in UtA were not significant.
      Hemodynamical findings of UmA, UmV and UtA were abnormal in 92.53% of IUGR
      patients. Only 81.03% present abnormal S/D ratio of UmA (P < 0.01) and the
      difference was statistically significant. Maternal serum E3, HPL level in IUGR
      were significantly lower than that of the normal. 6KP level was reduced, TXB2/6KP
      ratio was significantly increased. TXB2/6KP ratio was markedly related with TAV,
      Q of UmA, UmV and UtA. Our results suggested that using color doppler ultrasound
      for examination of hemodynamical changes of UmA, UmV and UtA could revealed UPFC
      function directly. It is one of the best methods for monitoring IUGR and might be
      used for early diagnosis of IUGR. The main pathophysiological changes of IUGR
      were UPFC obstruction and placental disfunction.

PMID- 9639803
TI  - Effects of cyclosporin A on proliferation of cultured rat mesangial cells.
AB  - The proliferation of mesangial cells on cyclosporin (CsA) test medium was studied
      by MTT assay and TNF-alpha in cultured supernatant was examined by using ELISA.
      The results showed that cyclosporin A significantly inhibited the proliferation
      of mesangial cells at the concentration between 0.25-15 micrograms/ml (IC50 1
      microgram). This action appeared to be dose-dependent. Release of TNF-alpha from
      mesangial cells stimulated by LPS was also dose-dependently suppressed. It is
      suggested that cyclosporin A play an important role in antiproliferation
      mechanism of mesangial cells in vitro.

PMID- 9639804
TI  - Tissue response and the cytoconduction ability to collagen/hydroxyapatite
      heterotopic implantation.
AB  - A histological and ultrastructural observation of CHA implanted intramuscularly
      and subcutaneously had been reported. Our results showed that a mild inflammation
      developed at the early stage and disappeared 2 weeks after implantation. The
      infiltrating cells were mainly monocyte-macrophages, a number of fibroblasts
      followed macrophages closely. It was possible that as CHA degrades, monocyte
      macrophages continuously released inflammatory factors, thus enhancing fibroblast
      proliferation activity and tissue regeneration. In addition, the heterotopic
      calcification of collagen matrix was observed, suggesting that CHA promoted
      calcification deposition.

PMID- 9639805
TI  - The factors related to fungal peritonitis in patients on peritoneal dialysis.
AB  - Fungal peritonitis (FP) is a serious infectious complication of peritoneal
      dialysis (PD). This retrospective study was conducted in 11 cases of FP among 64
      cases of patients with bacterial peritonitis (BP). Our results showed that age
      and sex underlying disease did not correlate significantly with the development
      of FP (P > 0.05), while long-term, repeated administration of antibiotics did (P
      < 0.01). It is suggested that the patients recently suffering from BP and being
      resistant to antibiotics were at great risk of suffering from FP. The key to
      prevent FP was to avoid BP, to use sensitive antibiotics with appropriate courses
      and to give nutritive treatment.

PMID- 9639806
TI  - Lipids, lipoproteins and apolipoproteins abnormalities in patients undergoing
      dialysis.
AB  - Twenty hemodialysis (HD) patients and 20 patients on continuous ambulatory
      peritoneal dialysis (CAPD) were investigated for lipids, lipoproteins and
      apolipoproteins abnormalities. HD patients had elevated serum triglyceride,
      decreased high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I
      (Apo A-I), while CAPD patients had elevated total cholesterol, triglyceride, low
      density lipoprotein cholesterol (LDL-C), Apolipoprotein B (Apo B), Apo B/Apo A-I
      ratio, and decreased HDL-C, Apo A-I. Because of the molecular sieving effects of
      peritoneum, CAPD have a negative effect on these abnormalities. CAPD patients
      might be at greater risk of developing coronary artery disease than HD patients
      who are also at increased risk as compared with normals.

PMID- 9639807
TI  - [Co-regulative effect of PKA-RII and PKC-alpha kinase subspecies on expression of
      c-myc and c-H-ras in human gastric cancer cells (MGC 80-3)].
AB  - Based on preceding experiment, we further studied the co-regulative effects of
      PKA-R II and PKC-alpha on expression of oncogenes in human gastric cell line MGC
      80-3. The c-myc and c-H-ras expression were suppressed in MGC 80-3 cells during
      HMBA-induced differentiation. At the same time, PKA-R II showed nuclear
      translocation from cytoplasm, whereas the expression of PKC-alpha shifted from
      nucleus to cytoplasm. PKA inhibitor (Sigma) was added to block cAMP-PKA pathway
      when cell differentiation were induced by HMBA. The PKA-R II was still located in
      cytoplasm but expression of PKC-alpha translocated again into nucleus. Meanwhile,
      the c-myc and c-H-ras again expressed. This suggested that the changing
      regulation of oncogene expression were closely related to signalling from nuclear
      translocation of kinase subspecies. It thus shows the co-regulation effects of
      two signal system on oncogenes expression.

PMID- 9639808
TI  - [Internalization of tumor associated antigen on human lung adenocarcinoma cell
      line SPC-A-1 by McAb LC-1].
AB  - Antigenic modulation of tumor cells is a kind of immunophenomenon that the
      antigenicity of tumor cell surface antigen could be lessened, weakened or
      completely lost. It is a potential route for tumor cells to escape the
      immunosurveillance and immunoattack of the host. One of the means to cause the
      antigenic modulation is by means of the antibody. In present research, gold
      labeled monoclonal antibody LC-1, which is raised against human lung cancer in
      our lab, as a molecular tracer to study the internalization and the subsequent
      fate of the membrane tumor associated antigen-LC-1 complex on the SPC-A-1 cell
      surface has been used. We found that this complex was internalized via the
      receptor-mediated endocytic pathway and concentrated in the multivesicular bodies
      and transported to lysosomes for proteolysis in the end. Strikingly, we noted
      that LC-1 had induced the autophagocytosis of ribosomes in SPC-A-1 cells in the
      median time it induced the internalization of the cell surface antigen cause by
      internalization and the restoration after antigenic modulation were also analyzed
      by the fluorescence activated cell sorter (FACS).

PMID- 9639809
TI  - [Apoptosis of HL-60 cells induced by Harringtonine: membrane blebs, nucleus blebs
      and chromatin condensation].
AB  - Using Video Enhancement Contrast (VEC) microscopy, we recorded the morphological
      changes of same HL-60 cell in the processes of apoptosis induced by
      harringtonine. Our results show that all of apoptotic cells need several nucleus
      blebs before their chromatin condensation. Every nucleus bleb is induced by a
      relative membrane bleb. The number of membrane blebs is much higher than that of
      nucleus blebs, so there are only some of membrane blebs which can induce nucleus
      blebs. It suggested that membrane and nucleus blebs probably are related to
      apoptotic chromatin condensation. After HL-60 cells pretreated with cytochalasin
      B(CB), apoptotic chromatin condensation delayed eight hours, but no membrane
      bleb, nucleus bleb and apoptotic body formed eventually. So membrane and nucleus
      blebs during apoptosis are related to microfilament re-organization and can
      accelerate apoptotic chromatin condensation, but are unnecessary for apoptotic
      chromatin condensation. All this suggested that nuclear changes and cytoplasmic
      changes during HL-60 cell apoptosis are independent.

PMID- 9639810
TI  - [Study on the transferring of YACs to new host by means of KAR cross].
AB  - The donor yeast strain YAC23 containing a 340 kb human genomic DNA fragment in
      YAC (Yeast Artificial Chromosome) was mated with recipient strain YLB504 by means
      of improved kar cross and the condidate YACductants were assayed by PCR and the
      amplification band of 404 bp indicated that they were the same as those of
      recipient strains (i.e. MAT alpha). Further analysis of the electrokaryotype of
      the candidate YACductants by PFGE (Pulsed Field Gel Electrophoresis) confirmed
      that the YACs had succeeded in entering into the recipient cells. The YACs had
      thus completed the process of transferring from one host to the other.

PMID- 9639811
TI  - [Cell-free nuclear assembly induced by nucleoli and demembranated macronuclei
      from Tetrahymena shanghaiensis].
AB  - Nuclei assembled in Xenopus egg extracts from exogenous DNA or chromatin are
      morphologically similar to normal eukaryotic nuclei except that they do not
      contain nucleolus-like structure. Previous work show that prenucleolar bodies
      could be found in these nuclei, but they are unable to fuse with each other,
      probably due to the absence of a functional nucleolus organizer. It is
      interesting to know if exogenous functional nuclei could act as functional
      nucleolus organizer to induce the formation of mature nucleoli. To test this
      possibility, nucleoli and demembranated macronuclei which contain perinuclear
      distributed nucleoli were isolated and purified from Tetrahymena shanghaiensis
      and were introduced into Xenopus cell-free system. By EM observation, we showed
      that these nucleoli, both individual isolated and perinuclear distributed, could
      not keep their original morphological characteristic, but undergo a series of
      structural changes resembling nuclear assembly induced by exogenous chromatin. No
      nucleolus-like structure was found in these nuclear like structure. These results
      indicate that functional nucleolus organizers could neither keep their original
      activity of RNA transcription nor induce the formation of new nucleoli in Xenopus
      egg extracts.

PMID- 9639812
TI  - [A novel conservative structure found in the carp mitochondrial tRNA(phe) gene].
AB  - A nucleotide sequence for the tRNA(phe) gene of Carp mitochondria was determined.
      Sequence data comparisons made among the whale, human, Xenopus laevis, bovine,
      mouse, chicken and carp, showed that a novel conservative structure was found in
      the D. stem (dihydrouridine stem), which was known had variant nucleotides in any
      other vertebrate mitochondrial tRNA and cytoplasmic tRNA genes. This conservative
      structures contains 13 bp. When we compared the front 7 bp of the conservative
      structure with the eukaryotic RNA Pol III recognitive A domain, we found these
      two kinds of different species had partly homologue. As the mitochondrial
      tRNA(phe) gene is located between the displacement loop and mitochondrial rRNA
      gene, we inferred that the novel conservative structure might have some extra
      interesting functions.

PMID- 9639813
TI  - [The mechanism of vasculogenesis: the critical role of transforming growth factor
      beta 1 in the formation of vessel-like structures during the differentiation in
      vitro of murine embryonic stem cells].
AB  - When ES-5 cells were transfected with an exogenous porcine TGF-beta 1 gene, one
      can obtain clones of genetically modified ES cells with over-expression of the
      transfected gene. We called the genetically modified ES-5 cells as ES-T cells.
      When ES-T cells were used to study their differentiation in vitro by all trans
      retinoic acid (RA), it was soon noticed that embryoid bodies of ES-T cells can
      exclusively differentiate into endothelial cells and vessel-like structures, but
      not in their parent ES-5 cells. The above result is the first indication that the
      differentiation of tubular structures in embryoid bodies of ES-T cells may
      somehow be related to TGF-beta 1. To demonstrate further the role of TGF-beta 1
      in the formation of vessel-like structures, the cultured ES-5 cells in the
      presence of added rhTGF-beta 1 were closely followed in the course of their
      differentiation. We have, thus, demonstrated the promoting effects of exogenous
      rhTGF-beta 1 in the formation of vessel-like structures, morphologically similar
      to those structures derived from ES-T6 cells, during the differentiation of ES-5
      cells, both in monolayer culture, in three dimensional collagen gel and in
      embryoid bodies cultured on gelatin-coated tissue culture wells. Addition of
      suitable amount of anti-TGF-beta 1 monoclonal antibody IgG (TB21) to the culture
      medium of embryoid bodies of ES-T6 cells could effectively abolish the formation
      of vessel-like structures induced by retinoic acid. The percentage of the
      inhibition was very high, giving a figure comparable to that of atypical vessel
      like structures formed in the control embryoid bodies from their parent ES-5
      cells. The flat epithelial-like cells and round cells differentiated from
      embryoid bodies of ES-T6 cells were stained rather strongly for laminin and type
      IV collagen by immunofluorescent procedure. The above results indicate clearly
      that TGF-beta 1 is a crucial factor in organizing the differentiated derivatives
      (endothelial-like cells and their immediate progenitor cells) from ES-T6 cells to
      form vessel-like structures, and that the role of TGF-beta 1 in vasculogenesis
      might be performed, in part, through the modulation of the composition and
      organization of the extracellular matrix. In addition, the enhanced expression of
      bFGF mRNA in derivatives differentiated from both ES-5 cells treated with rhTGF
      beta 1 and ES-T6 cells were detected by Northern blot analysis. Thus, aside from
      its effects on extracellular matrix, TGF-beta 1 might also modulate the
      bioactivity of bFGF in relation to the growth of vascular endothelial cells in
      the present system.

PMID- 9639814
TI  - [Cloning and screening on tumor-related genes inactivated in rat hepatoma cells.
      II. Reversion of malignant phenotype of hepatoma cells].
AB  - A rat normal expressing cDNA library was established and subsequently its whole
      DNA was transfected into CBRH-7919 rat hepatoma cell cultures. With neomycin
      selection and morphological distinction, several reversed colonies were isolated
      and subcloned. All these colonies showed decreased growth rates, reduced capacity
      for foci formation on soft agar and tumorigenicity in nude mice compared to CBRH
      7919. Analysis of rescued plasmid cDNA from these colonies is under way.

PMID- 9639815
TI  - [A retrotransposon-like element Tca1 was used for taxonomic determination of
      Candida albicans].
AB  - We had isolated from Candida albicans a moderately repetitive sequence designated
      alpha and a retrovirus-like transposable element Tcal (Transposon Candida
      albicans). The Tcal consisted of two 388bp direct repeats of the alpha element,
      called LTR (Long Termination Repeat), which was separated by approximately 5.5kb
      of DNA. A large number of strains from America and China have been grouped based
      on patterns of hybridization bands visualized on Southern blots of EcoRI digested
      genomic DNA probed with alpha and Tcal element internal sequence. Strains from
      same area have higher relatedness than those from different area. The
      hybridization patterns with URA3 and other DNA probes were also conserved within
      the groups. alpha element are species specific, no hybridization was observed
      with genomic DNA of other yeast species. The data presented here indicate that
      the alpha element can be employed to distinguish between species and to assess
      strain relatedness within C. albicans, we suggest that Tcal may be relevant to
      the genomic evolutions of C. albicans and the pathogenic potential of the
      organism.

PMID- 9639816
TI  - Essential region for self-replication of Coryneform bacteria plasmid pXZ10145.
AB  - A pTSK series of recombinant plasmids were constructed by cloning DNA fragments
      of pXZ10145 or its deleted deriviate pATN65 into plasmid vector pACYC177 of E.
      coli. Experiment results of Coryneform bacteria transformation with these pTSK
      plasmids allowed us to localize the essential region for self-replication on
      plasmid pXZ10145. The minimal replication region of the pXZ10145 was located on a
      1.2kb Nael-Nrul DNA fragment in which only one open reading frame was found. This
      ORF was believed to be encoded a trans-acting replication factor. The replication
      origin (oriV) was locate on a 0.3kb NaeI-SalI fragment which was within the ORF
      region.

PMID- 9639817
TI  - Cloning and expression of full-length delta-endotoxin cryIA(c) gene in three
      kinds of prokaryotic systems using shuttle vector pHT3101.
AB  - Two fragments, 6.5kb and 4.3kb encoding 5' end and 3' end of delta-endotoxin
      cryIA(c) gene, respectively, were selected from the Bacillus thuringiensis
      kurstaki-HD-73 75kb plasmid gene pool using random primer labelling delta
      endotoxin cryIA(b) gene probe. The full-length 3.92kb cryIA(c) gene including 5'
      end 152 bp promoter sequence and 3' end 198 bp terminater sequence was rebuilt
      after uncoding sequences were deleted. Three kinds of engineering strains
      harbouring the same recombinant plasmid pHTY1 were obtained after the cryIA(c)
      gene had been subcloned in shuttle vector pHT3101 and transformed to E. coli
      NM522, Bacillus subtilis AS1176 and Bacillus thuringiensis crystal-deficient
      4D10(H3ab). SDS-PAGE electrophoresis patterns reveal that the cryIA(c) gene
      expressed the same 133,300 protoxin proteins in all three host systems with the
      same molecular weight to the crystal protein from the Bacillus thuringiensis
      kurstaki HD-73. Immuno-assays indicate that the expression proteins can react
      with antiserum of HD-73 paraspore crystal protein in the same pattern as the
      natural crystalprotein. Bioassays using crude expressed products from three host
      strains reveal that they all showed toxicities to second instar larvae of
      Plutella xylostella, and their LD50 were calculated to be 0.311 micrograms/cm2,
      0.02 micrograms/cm2 and 0.017 micrograms/cm2, respectively.

PMID- 9639818
TI  - [Immunogenicity of recombinant S. typhimurium ex. pressing a hybrid antigen of
      Plasmodium falciparum].
AB  - We have expressed a 74-peptide hybrid Plasmodium falciparum antigen as fusion
      protein in attenuated Salmonella typhimurium SL3261. Live organisms were orally
      immunized Rabbits with a dose of 2 x 10(9)cfu. Specific anti-serum were detected
      by ELISA after immunization. Obvious Delayed type hypersensitivity (DTH) could be
      induced by PfAg and GZ-C antigen. The recombinant vaccine had no evident side
      effects to the hosts. Our studies indicate that attenuated Salmonella typhimurium
      SL3261 can express synthetic P. falciparum antigen with several epitopes and live
      organisms can activate special cell-mediated immunity and humoral immunity.

PMID- 9639819
TI  - [Studies on midecamycin 4"-O-propionyltransferase gene structure].
AB  - A BamHI-BamHI 8.0 kb DNA fragment which contains midecamycin propionyltransferase
      (mpt) gene was digested with different restriction enzymes and the restriction
      map was made. The mpt gene was localized in a EcoRI-EcoRI-PstI3.0 kb DNA fragment
      by Southern blot analysis using a 2.4 kb DNA fragment of the CarE gene as a
      probe. The 3.0 kb DNA fragment of mpt gene was cloned into E. coli/Streptomyces
      shuttle vector pWHM3 and a recombinant plasmid pWFPE was obtained. S.
      ambofaciens(pWFPE) and S. lividans(pWFPE) can convert endogenously synthesized or
      exogenously added spiramycin into 4"-O-propionylspiramycin, respectively.
      Sequence analysis of mpt gene demonstrated an open reading frame in the EcoRI
      EcoRI-PstI3.0 kb DNA fragment, which starts with ATG and ends with TGA. Mpt gene
      encodes a product of 388 aa. G+C mol% of mpt is 68.0 and G+C mol% of 3rd codon
      position is 91.5. The putative product of mpt has a identity of 67.6% and a
      similarity of 86.4% with CarE product. A consensus RBS GAGGT in the 6bp upstream
      from ATG and a promoter region were found. An inverted repeat sequence in the
      downstream from TGA acts as transcriptional terminator.

PMID- 9639820
TI  - [A legionella pneumophila strain serologically cross-reacting with thirteen
      serogroups of this species].
AB  - A bacterial strain, designated as Jin-1, was isolated from a water sample taken
      from the Jinyang Lake located in the suburbs of Taiyuan City, Shanxi Province.
      Its morphologic and tinctorial properties, nutritional requirements, growth
      characteristics, biochemical reactions, as well as results of DNA and peptide
      analysis overall met the criteria for identification of Legionella pneumophila.
      In serogrouping, extensive cross-reactions between Jin-1 and the type strains of
      L. pneumophila serogroup 1 through 14 were observed in both slide and tube
      agglutination tests mediated by the IgM antibodies. However, Jin-1 revealed the
      L. pneumophila serogroup 5 specificity in IFA, ELISA and dot-ELISA, all mediated
      by the IgG antibodies. Jin-1 was finally identified as a strain of L. pneumophila
      serogroup 5 with the more complex antigenic composition than the ATCC type strain
      of this serogroup. The taxonomic conclusion has been confirmed by CDC. A
      Legionella pneumophila strain which serologically cross-reacting with so many
      serogroups of this species has never been reported in the published articles. It
      is presumed that the cross-reacting antigen of Jin-1 belongs to the thymus
      independent antigen by nature.

PMID- 9639821
TI  - [Studies on some characteristics of a strain of mink infectious enteritis virus].
AB  - A strain of mink infectious enteritis virus that was isolated from the east
      district of China can be bred on FK cell. Concentrated viruses were purified by
      using Sepharose-4B chromatography. The size of the virus was about 20-22 nm by
      electron microscope. Viral nucleic acid was extracted from pure virus by using
      SDS-protease K-Phenol. Tests with diphenylamine, acridine orange and the curve of
      thermal dentuation, etc. showed that the virus had a single-stranded DNA. The
      molecular weight of the ssDNA was from 1.5 x 10(6) to 2.0 x 10(6) determined by
      length of the virul nucleic acid.

PMID- 9639822
TI  - [Microcolony observation for rapid detection and identification of cultures of
      Mycobacterium tuberculosis].
AB  - 219 sputa were seeded on Kuang's agar plates. A total of 112 isolates of
      Mycobacterium tuberculosis were detected in 219 specimens. Of these 112 isolates,
      104 (92.8%) were detected in Kuang's agar media and 108 (96.4%) were detected by
      microcolony observation. The detection time of microcolony observation and
      culture method needed 11 and 18.6 days respectively. The detection time of
      microcolony method is much shorter (P < 0.001). The results of conventional tests
      of different species of Mycobacterium and microcolony differentiation were
      identical in 99% of isolates of Mycobacterium tuberculosis.

PMID- 9639823
TI  - [Studies on modulation and control sigma 38 and RMF for the expression of some
      genes].
AB  - The E. coli mutants and wild type strains of rpoS and rmf were cultured in rich
      medium LB and limited component medium EP respectively. During the stationary
      phase, the viable cells of mutants were less than wild type strains's. The change
      of the product of serial proteins was quantified with Western blot. Sigma 38 has
      not effects on the product of rpoA, rpoB, rpoC, groE and tu gene, depress the
      transcription of crp and promote the expression of rmf. RMF can promote
      expression of rpoA, rpoD, groEl, rho, ompA and tufA gene in rich medium, but not
      in limited medium, and then depress and promote the expression of crp and rpoS
      respectively.

PMID- 9639824
TI  - [A new zoonosis--investigation of Gardnerella vaginalis disease of fox. V.
      Studies serotype of Gardnerella vaginalis in fox].
AB  - 145 strains Gardnerella vaginalis isolated in foxes were isolated from 13 main
      farms raising foxes in six provinces (regions), China, after antigenicity and
      immunogenicity of the strains were measured, 1-3 appropriate strains were
      selected from each farm raising foxes for serotype studies. Cross agglutinin
      absorption test confirmed that selected 26 strains Gardnerella vaginalis were
      divided into three serotypes and then the representing strains were used to
      produce typing serum. Among remaining 119 strain, 108 strains were typable with
      the typing sera, and 11 strains can't be set. Among three serotypes, serotype I
      made up 79.1% of the strains. It was shown that serotype I was the principal
      serotype of Gardnerella vaginalis of fox in China. The test also confirmed that 5
      strains of Gardnerella vaginalis isolated from racoon dog, 4 strain Gardnerella
      vaginalis from mink and 2 strains Gardnerella vaginalis from canine also belonged
      to serotype I. Supersonic antigben was produced with three serotypes,
      representative strains. By agar immuno-diffusion test, it confirmed that the
      antigens of three serotypes formed a obvious blending precipitating line with the
      homologous or heterologous serotype antiserum. It indicated common antigen
      existed among all serotypes. The agar immuno-diffusion test results revealed that
      the precipitating line of the homologous serotype completely blended. It is our
      opinion that the method of serotyping is reliable.

PMID- 9639825
TI  - [Analysis of surface antigen molecule expression on serovar stains of Neisseria
      gonorrhoeae by flow cytometry].
AB  - In the present experiment, flow cytometry was employed for analysing expression
      characteristics of the antigen molecules distingushed by 10 monoclonal antibodies
      against Neisseria gonorrhoeae lipooligosaccharides. Stability of antigen
      expression and amount of epitope on the surface of N. gonorrhoeae were
      quantitative determined. Reactivity of the monoclonal antibodies with serovar
      strains of N. gonorrhoeae were evaluated.

PMID- 9639826
TI  - [Study of relationship between the bacteria in air and the clinic infection].
AB  - The Source of infectious bacteria is the first problem in provension of infection
      considered by the medical workers. In this paper, with the method of bacteria
      plasmid analysis, chromosome DNA restriction fragment length polymorphism
      analysis, drug resistance experiment (antibacterial drug, sterilizing drug) and
      so on. We confirmed that staphylococci of nosocomi is mainly from air; but the
      gram-negative bacteria is mainly from the patient's pharyngeal portion; and cause
      hospital infection indirectly. The drug resistance of gram-negative from air was
      lower than the same gram-negative bacilli's isolated from the patient. Moreover,
      kill bacteria the infectious strain is same strain in air. Above-mentioed results
      provided the important basis for control of the hoslpital infection.

PMID- 9639827
TI  - [Regulation of purine biosynthetic genes expression in Salmonella typhimurium. V.
      Nucleotide sequences evidence without purJ gene].
AB  - Previous genetic analysis showed that AICAI transformylase, IMP cyclohydrolase
      and GAR synthetase are encoded by purJ, purH and purD respectively, and which
      constitute a operon, mapped on 90 min in genetic map of Salmonella typhimurium
      But recent study in E. coli indicated that the genes encoding for above three
      enzymes only have purH and purD, without purJ gene. Report here is the DNA
      sequences evidence for abence of purJ gene in Salmonella typhimurium.

PMID- 9639828
TI  - [Cloning and identification of fliCi gene of Salmonella typhimurium].
AB  - Purified Salmonella typhimurium 8705 chromosomal DNA was digested with EcoRI. DNA
      fragments above 400 bp were obtained by Sepharcyl S-400 chromatography and cloned
      into vector pGEM-3Zf(-), then transformed into host cell LC2a (hag- is recA-).
      One out of 6013 transformants was found to be motile and this clone was named
      pGI4015. Miniprep proved that pGI4015 contained an inserted fragment about 15.3
      kb. Motility/inhibition tests as well as Southern blot hybridization showed that
      pGI4015 bear the H-1i gene of S. typhimurium. With the aid of BamHI and SalI
      site, sequences unrelated to flagellin in the cloned DNA fragment was removed,
      and a 3.8kb fragment containing fliC gene was subcloned.

PMID- 9639829
TI  - [Studies on purification and some properties of nisin from Lactococcus lactis
      subsp. lactis Al2].
AB  - Nisin from Lactococcus lactis subsp. lactis AL2 was extracted with n-propanol
      from NaCl-saturated culture and purified by ion-exchange chromotography on CM
      Sephadex C-25. Nisin was purified 1.63 fold with a yield of 41.7%. The molecular
      weight of nisin was determined by SDS-PAGE to be about 3500. Nisin activity was
      stable at low pH and sensitive to digestion by a-chymotrypsin. Nisin is capable
      of inhibiting a broad range of gram-positive bacteria. In contrast, the gram
      negative bacteria, yeasts, molds and Nip+ L. lactis subsp. lactis ATCC11454 were
      not inhibited.

PMID- 9639830
TI  - [An experimental animal model study of HCMV].
AB  - This Paper is a study of animal model on the Kunmin and BALB/C mice infected HCMV
      AD169. The death-rate showed a marked higher BALB/C mice (28.75%) than the kunmin
      mice. The Kunmin mice Percentage of diseased (94.74%) higher than BALB/C mice.
      Brian tissue of two groups mice that pathological changed was equal by HCMV
      infected.

PMID- 9639831
TI  - [Distribution of Bacillus thuringiensis in soils of north and south of China].
AB  - 221 isolates of Bacillus thuringiensis were isolated in 1491 soil samples from
      North and South of China. H-serotypes and larvicidal characters of all Bt
      isolates have been identified. The rate of Bt-harbouring soil sample and the rate
      of Bt isolates in Northeast and Neimeng were in 12.6% and 17.2% respectively.
      Predominant serotypes were H4, H10, H3, H13, H5 and H29. The most fertile Bt
      harbouring area was the Heilongjiang Province with rate of Bt-harbouring sample
      of 21.4% and rate of Bt isolate of 29.4%. Rate of Bt-harbouring sample and rate
      of Bt isolate in Northwest area were 6.6% and 7.1% respectively. Main serotypes
      were H4, H5, H19, H10 and H3. In four provinces of Southern China, both rates
      above were 18.6% and 29.5%, but frequency of Bt distribution was varied seriously
      in different distinct. Predominant serotypes in soils from Southern China were H3
      and H5. Results of bioassay showed that the percentage of strains high active to
      Heliothis armigera and Plogioidera versicolora were 1.6% and 1.1% in soils from
      North of China. In contrast to North of China, Bt strains active to H. armigera
      were 5.3% and none of Bt was effective to P. versicolora in South of China. A
      strain H27-05 was high toxic to H. armigera and showed temperate toxicity to P.
      versicolora.

PMID- 9639832
TI  - [Characterization of insecticidal crystal proteins of Bacillus thuringiensis
      subsp. chinensis CT-43].
AB  - Bacillus thuringiensis subsp. chinensis CT-43, no flagellum, produces various
      shaped parasporal crystals, which consist of 140000, 130000, and 65000 proteins.
      Based on two kinds of mutant, 140000 and 130000 crystal protein individually
      forms bipyramidal crystal and the 65000 protein forms cubidal crystal, and that
      the 140000 and 130000 protein is activated by trypsin into 55000 and 66000
      proteins and 60000 protein, respectively. Bioassay were conducted to 3rd instar
      Plutella xylostella larvae with crystals, soluble crystal proteins, and activated
      crystal proteins, respectively, and it indicated that high toxic mutants can be
      obtained by curing low toxic crystal genes, and that the toxicity of crystals can
      be improved 16.3 to 58.4 times after solubilization.

PMID- 9639833
TI  - [Preliminary research on Bifidobacterium cuniculi in stomach and intestines of
      rabbits].
AB  - The distribution of Bifidobacterium in stomach and intestines of ten healthy
      rabbits were studied by microecological methods. The results showed that
      Bifidobacterium exist in stomach, small intestine and large intestine, the amount
      hightest in large intestine, second in jejunum and no finnd in duodenum. Being
      isolated, purified and biologically identified, the bacteria was identified as
      Bifidobacterium cuniculi, whose other biological characteristics also was
      studied.

PMID- 9639834
TI  - A population-based study of lens opactities.
AB  - PURPOSE: Age-related lens opacity is the main cause of vision disability in
      elderly population all over the world. This study was designed to investigate the
      prevalence and incidence of lens opacity. METHODS: 1817 eyes of 932 adults over
      45 years-old were sampled randomly from 4 villeges within Doumen, a county
      located in the south of Guangdong provience, China. The procedure of the
      examination was performed by ophthalmologists. The lens opacities were graded
      according to a standarized photo of the Lens Opacities Classification System II
      (LOCS-II). RESULTS: The prevalence of lens opacities in nuclear color, nuclear
      opacity, cortical opacity and subcapsular opacity was 16.1%, 28.6%, 30.3% and
      8.7%, respectively. The frequency of all four types of opacities increased with
      age. The prevalence of lens opacities in four types was higher in female than
      that in male. CONCLUSION: The data we got are important for prevalence of lens
      opacities of population-based study as well as basic information for cohort study
      in the future.

PMID- 9639835
TI  - The etiology of vision impairment in target population.
AB  - PURPOSE: research the etiology of vision impairment in target persons over 45
      years old in Doumen county, Guangdong province. METHODS: Depending on the
      prevalences of the blindness among the person aged over 50 years, the theoretic
      sample rate is 1,000/4,8733 x 100% = 2.05%. The 8 districts were divided into 3
      parts according to the local economic situation and the proportion of the
      population in the areas. In fact, the sampling rate is 932/10055 = 88.34%.
      RESULTS: We found that impairment < 0.3 accounted for 10.94%. The prevalence of
      bilateral blindness and low vision was 1.61% and 3.22%, respectively. Both
      prevalences of blindness and low vision were increased with age. The leading
      cuase of blindness was cataract (45.2%). The second was corneal opacity (16.7%).
      Prevalences of the low vision and the blindness were higher in females than in
      males (P < 0.005). CONCLUSIONS: Curable and preventable diseases were the leading
      cause for the blindness (70%). Prevalences of blindness and the low vision
      increase with age. We will continually follow up the population over 50 years of
      age in Doumen county.

PMID- 9639836
TI  - Relationship between myopia and optical components--a study among Chinese Hong
      Kong student population.
AB  - PURPOSE: To establish the prevalence and severity of myopia among the Chinese
      Hong Kong students and to study the relationship between myopia and optical
      components. METHODS: One thousand and seventy-five freshmen of the 1993-1994
      academic year in the Chinese University of Hong Kong underwent the eye
      examination including evaluation of refractive error, keratometry, and A-scan
      ultrasonic biometry. The data were analyzed with the SPSS/PC+4.01 statistical
      package. RESULTS: The prevalence of myopia was 91.7% with the mean refraction
      being -4.00 +/- 2.64D in this young adult population. The statistical analyses
      demonstrated a significant correlation between refractive value and axial length
      of the globe (r = -0.78), vitreous length (r = -0.76), anterior chamber depth (r
      = -0.33), lens thickness (r = 0.13) and corneal curvature (r = 0.19). CONCLUSION:
      The refractive status is mainly dependent on the axial length. In general, the
      higher the myopia was, the longer the eyeball, the deeper the anterior chamber,
      the steeper the cornea, and the thinner the lens would be.

PMID- 9639837
TI  - A dynamic and quantitative study of pattern visual evoked potentials and gamma
      aminobutyric acid neurones in the lateral geniculate nucleus and the visual
      cortex of monocular deprivation cats.
AB  - PURPOSE: To assess the effects of monocular lid closure during critical period on
      cortical activity. METHOD: Pattern visual evoked potentials (PVEP) of the normal
      and the monocular deprivation (MD) cats were dynamically measured and the number
      of gammaaminobutyric acid immunopositive (GABA-IP) neurones of the area 17 of the
      visual cortex and the lateral geniculate nucleus (LGN) was quantitatively
      compared by using immunohistochemical method (ABC). RESULTS: The amplitude of the
      N1-P1 attenuated in deprived eyes (DE), NE/DE at postnatal week (PNW) 7-8 (P <
      0.05), NE/DE at PNW 15-16 (P < 0.01); while P1 latency delayed, NE/DE at PNW 7-8
      (P > 0.05), NE/DE at PNW 15-16 (P< 0.05). The numbers of GABA-IP neurones in
      layer A1 of the ipsilateral LGN and in layer A of the contralateral LGN, compared
      to those in the corresponding normal laminae, were not significant at PNW 7-8 and
      PNW 11-12 (P > 0.05), while in the same cats a reduction in the number of GABA-IP
      neurones was found in layer IV of area 17 at PNW 11-12 (P < 0.05). However, with
      longer survival of 3-4 weeks in duration, the numbers of GABA-IP neurones in the
      deprived laminae of LGN were remarkably reduced (P < 0.05). CONCLUSIONS: The
      amplitude of N1-P1 components is sensitive to the effects of monocular
      deprivation. Monocular deprivation in cats during critical period leads to
      dramatic changes of the number of GABA-IP neurones in the LGN and cortical layer
      IV receiving inputs from the deprived eye in cats. The deprivation-induced
      reduction in GABA-IP neurones is delayed in the LGN compared with the visual
      cortex. PVEP of the MD cats is consistent with the damage of its GABA system in
      visual cortex.

PMID- 9639838
TI  - The visual deprivation and increase in axial length in patients with cataracts.
AB  - PURPOSE: To investigate the relationship between axial myopia and visual
      deprivation in patients with cataracts in their youth. METHODS: Forty myopic eyes
      of 25 cases had long deprivation of form vision due to cataracts during their
      youth. The axial length was measured by A-Scan ultrasound. RESULTS: The axial
      length is 2-6mm (mean: 3.7mm) longer than the other eyes in 10 patients with
      unilateral cataracts. Fifteen cases with bilateral cataracts had 25-29mm of axial
      length (mean of the right eyes 26.8mm and the left eyes: 26.7mm). Six cases with
      unilateral cataract had traumatic history at age from 2-9 years (mean: 5.1 years)
      and the duration of visual deprivation due to cataract was from 8 to 30 years
      (mean: 12 years). Thirteen cases with dilateral congenital cataract had 17.4
      years (from 3 to 37 years) of visual deprivation. CONCLUSION: The deprivation of
      form vision due to cataracts in childhood leads to increase in axial length and
      myopia.

PMID- 9639839
TI  - Refractive changes in chicks with form-deprivation myopia.
AB  - PURPOSE: To study the refractive changes of form deprivation of myopia. METHODS:
      Haisaik chickens were used to establish the animal models of myopia. Monocular
      eyelids were sutured for form deprivation on the 5th day after chickens birth.
      The chickens were examined by optometer and the anteroposterior axis, transverse
      and vertical diameters were measured by verniermicrometer. RESULTS: Form
      deprivation leads to myopic refractive abnormality (P < 0.001). The ocular
      anteroposterior axis (P < 0.005), transverse and vertical diameters lengthen (P <
      0.05). CONCLUSION: Form deprivation is the main cause of the development of
      myopia.

PMID- 9639840
TI  - Surgical management of macular epiretinal membranes.
AB  - PURPOSE: To evaluate the effects of surgical treatment on macular epiretinal
      membranes. METHODS: Vitrectomy and membrane removal were undergone for idopathic
      secondary macular epiretinal membrane. RESULTS: Fourteen eyes of 15 patients
      (93%) had vision improvement after operation in which 8 eyes (57%) increased 3 or
      more Senellen lines. Only one case suffered from paracentral scotoma. No other
      complications were noted. CONCLUSION: Surgical management of macular epiretinal
      membrane is safe and effective with good visual outcome and few complications.

PMID- 9639841
TI  - In vivo observations and electron microscopy of treatment of experimental HSV
      keratitis with anti-HSV monoclonal antibodies.
AB  - PURPOSE: To study the antiviral activity of monoclonal antibodies (McAb) in vivo
      and identify their effects on experimental herpetic keratitis. METHODS: Topical
      use of anti-HSV monoclonal glycoprotein antibodies was carried out on acute
      herpetic keratitis of rabbits infected by HSV-1 SM44. The application of the eye
      drops in each group was five times per day for 14 days by double-blind method. In
      vivo observation and electron microscopy were performed during the whole
      procedure. The anti-HSV McAb's solution was mixed up of five monoclonal
      antibodies with high neutrilization titers and/or high ADCC activity. RESULTS:
      Compared with placebo-treated eyes, anti-HSV McAb treatment made statistically
      significant reduction of herpetic corneal epithelial lesion on rabbits from day 3
      to day 14 postinnoculation (P < 0.01). Punctate and short dendritic lesion were
      the main patterns. The area of involvement was also limited. Electron microscopic
      analysis showed ultrastructural changes of herpetic corneal infection. The
      clumping of nuclear chromatin, swollon nuclei, reduction of microflament,
      rounding of epithelial cells were apparent in placebo-treated eyes. The advanced
      lesion of the viral infection was karyolysis, karyoklasis and disruption of cells
      in both scanning and transmission electron micrographes. The management of the
      McAb-treated eyes showed that the pathological involvements as mentioned above
      reduced remarkably. CONCLUSION: Topical application of anti-HSV monoclonal
      antibodies produced marked antiviral effects in inhibiting the development of
      experimental herpetic keratitis in rabbits and in protecting the susceptible
      corneal cells. As a new biological product, the anti-HSV monoclonal antibodies
      may provide a new approach to the treatment of HSV keratits.

PMID- 9639842
TI  - Detection of RB germline mutations using exon-by-exon heteroduplex analysis
      compared with SSCP.
AB  - PURPOSE: To compare heteroduplex analysis with SSCP and to develop a simple and
      effective method for mutational screening of RB gene. MATERIALS AND METHODS:
      Leukocyte DNA was prepared from 12 unrelated Japanese patients with hereditary
      retinoblstoma. PCR combined with simultaneous nonisotopic heteroduplex and SSCP
      analysis was used to screen leukocyte DNA for such mutations, exon-by-exon,
      without the use of restriction endonuclease digestion. PCR was conducted using 28
      pairs of primers flanking all 27 exons and the promoter region of the RB gene,
      with PCR products ranging from 159bp to 326bp. Mutations were identified by
      sequencing. RESULTS: Heterozygous germline mutations were detected in 8 of 12
      Japanese patients. The mutations were identified by sequencing as follows: G-
      >C/acceptor of exon 11, T insertion/codon 389, C-->T/codon 455, 33bp
      insertion/codon 455 (C decreases GA), G-->T/codon 533, C-->T/codon 579, C
      deletion/codon 674, and C-->T/codon 787. CONCLUSION: Our results suggest that
      small RB gene mutations are common. Heteroduplex analysis has advantage over SSCP
      and they may complement each other for the rapid detection of unknown mutations.

PMID- 9639843
TI  - Combined argon and Nd: YAG laser peripheral iridectomy: A new approach in
      clinical practice.
AB  - PURPOSE: To evaluate the therapeutic effect of combined argon and Nd: YAG laser
      peripheral iridectomy. METHODS: 151 cases (200 eyes) of primary angle-closure
      glaucoma and combined glaucoma were treated by combined procedure. Argon laser
      was the first used to create partial iridectomy in 2/3-3/4 thickness without
      penetrating pigmented epithelium, and then Nd: YAG laser was required to complete
      a patent iridectomy. RESULTS: A successful iridectomy was achieved in all
      patients independent of any type of irides (100%). Iris penetration rate in one
      session presented in 95.0%. Complications appeared to be less common in our
      patients: iris bleeding was only seen in 5.0% cases; the postoperative
      inflammation was mild; corneal burns, localized lenticular opacities and closure
      of iridectomies were less frequent. The follow-up ranged from 3m to 6.5 years.
      The success rate in controlling IOP with/without medications were 99.0% except 2
      eye failure. No attack occurred in 129 eyes with prophylactic laser therapy
      during the periods of follow-up. CONCLUSION: Combined procedure had much more
      advantage over either the argon or Nd: YAG laser iridectomy. It tended to be more
      preferable for Asian patients with heavily pigmented and thick irides.

PMID- 9639844
TI  - Corneal topography research of myopia in Chinese.
AB  - PURPOSE: To determine corneal topography parameters of myopia in Chinese and help
      for studies of causes of myopia, distingiush other corneal diseases (such as
      early keratoconus), further explore the accurateness and safeness of the clinical
      effects of radil keratotomy (RK) or photorefractive keratectomy (PRK). METHODS:
      Fifty-eight eyes with mild or moderate myopia were examined by computer-assisted
      photokeratography. (TMS-1 Computed Anatomy Inc. New York. NY) RESULTS: The
      corneal topography of most (68%) of the examined eyes showed symmetric bowtie
      pattern: the corneal surface of most (75%) of the examined eyes showed positive
      aspheric shape (steeper centrally, flatter peripherally); the refractive power of
      central cornea is at mean 44.165 +/- 1.429 D; the refractive difference between 1
      to 25 ring in keratoscpe was at mean 1.655 +/- 0.785D; the mean SRI was 0.558 +/-
      0.768, the mean SAI was 0.296 +/- 0.149; the mean Smik was 44.209 +/- 1.515D. The
      apex and visual axis were dislocation in all the cornea examined. CONCLUSIONS:
      The corneal surface refractive characterization of myopia might be relative to
      the clinical effects of RK or PRK.

PMID- 9639845
TI  - Ocular symptoms of tumors at sella turcica region.
AB  - BACKGROUND: The sella tumors were found in 15% of intracranial tumors. The sella
      turcica region locates in the base of skull, so the carcinoma patients in early
      stage often showed no intracranial hypertension and other positive signs of
      neural system. However, the patients presented visual field defect and hypopsia,
      and often went to see the doctor of ophthalmology, which resulted from that the
      tumor often compressed optic nerve and chiasm. We analysed the symptomatic
      changes of the visual organs in order to provide a diagnostic basis for sellar
      tumor in ophthalmological department. CLINICAL MATERIALS: Of the 407 cases of
      sellar tumors, 296 were pituitary adenoma, 52 were craniopharyngioma, 43 were
      meningioma, and the rest 16 were other kinds of sellar tumors. We analysed their
      ocular changes of the sellar tumors and the characteristics of the tumors.
      RESULTS: The sellar tumor in its early stage is mainly symptomized as visual
      field changes. Visual field defect was found in 92.9% of pituitary adnoma, 75% of
      craniopharyngioma and 34.8% meningioma patients. The patients of intermediate and
      later sellar tumors gradually manifested the hypopsia and optic atrophy. Hypopsia
      was found in 86.5% of pituitary adenoma patients, 89.9% of craniopharyngioma and
      48.8% of meningioma patients. The morbidity rate of optic atrophy is 59.5% in
      patients with pituitary adenoma, 65.5% of craniopharyngioma and 44.1% of
      meningioma. CONCLUSION: The misdiagnostic rate of sellar tumor in
      ophthalmological department still keeps comparatively high. The reason is that:
      (1) The doctors lack the neuroophthalmological knowledge. (2) The patients were
      not examined attentively enough. The ocular symptoms of sellar tumors are often
      the first occurred and most important changes. In the clinical practice, all the
      patients showing visual acuity and visual field disturbances should be examined
      carefully (especially in visual field) and excluded ocular diseases, should be
      transferred to the department of neurosurgery for further diagnosis and
      treatment.

PMID- 9639846
TI  - [Dynamic changes in soluble interleukin-2 receptor levels after rat corneal
      allograft].
AB  - PURPOSE: To evaluate the diagnostic utility of serum IL-2R level test in corneal
      allograft rejection. METHODS: Serum soluble IL-2R was detected by
      radioimmunoassay in rat corneal allograft model. RESULTS: Levels of soluble IL-2R
      were markedly elevated prior to the clinical diagnosis of rejection. CONCLUSIONS:
      Marked elevations of soluble IL-2R are associated with rejection, measurement of
      soluble IL-2R may have a useful value in the early diagnosis of corneal allograft
      rejection.

PMID- 9639847
TI  - [Relationship between expression of P21ras and cellular DNA in pleomorphic
      adenoma of lacrimal gland].
AB  - BACKGROUND: The pleomorphic adenoma is the most frequent tumor of the human
      lacrimal gland comprising about 50% of the epithelial tumors of this organ.
      Although being benign, local recurrences can occur when the first removal was
      incomplete and malignant transformation is also not in frequent. It is well known
      that many sorts of cellular oncogene products are involved in the initiation,
      promotion and progression of the human neoplasm. Our purpose was to know whether
      there is abnormal expression of P21ras in pleomorphic adenoma. METHODS: We have
      undertaken a study of the expression of P21ras in 5 normal tissues and 32
      pleomorphic adenoma of lacrimal gland by immunohistochemical means using the
      monoclone antibody F-132-62 and the nuclear DNA content in the tumor was assayed
      by image analysis technique. RESULTS: Normal tissues of lacrimal gland were
      negative, 12 tumors were stained positively with the antibody. The DNA content of
      14 cases of tumor was increased. Their DNA ploidy distribution pattern showed two
      or several peaks. Good correlation has been found between the expression of
      P21ras and DNA ploidy distribution pattern, the DNA ploidy distribution pattern
      of tumor which expressed p21ras showed mainly two or several peaks. P< 0.05.
      CONCLUSIONS: The result of our studies may suggest that there are increased
      expression of p21ras in pleomorphic adenoma and the expression of p21ras is
      related to the promotion and progression of pleomorphic adenoma of lacrimal
      gland.

PMID- 9639848
TI  - [Study of pathogenesis of age-related macular degeneration].
AB  - OBJECTIVES: To explore the pathogenesis of age-related macular degenerastion
      (AMD) for its early prevention and treatment. METHODS: The enzymes of red blood
      cells, levels of serum mineral elements and antiretinal antibodies were
      determined in AMD and controls. Electronic microscopy, immunohistochemical survey
      of the AMD patient subretinal neovascular membrane were performed. The light
      exposure of animal experiment was also made. RESULTS: The levels of superoxide
      dismutase and catalase as well as serum zinc were decreased in AMD patients, the
      ratio of copper and zinc was increase. The retinal antibody reaction was higher
      than that of controls, and the subretinal neovascular membrane showed
      inflammatory granulomatous appearance. CONCLUSIONS: In addition to age, AMD may
      be related to light damage, change in human defense system and chronic
      inflammatory process.

PMID- 9639849
TI  - [The study of the biological character on the culture of human trabecular
      meshwork cells in vitro].
AB  - PURPOSE: To establish the culture of human trabecular cells in vitro and to study
      their biological character. METHOD: The trabecular specimens from human eyes were
      cultured. The morphologic features of cultured cells were examined by light and
      electron microscopy, the immunohistochemical characteristics and the
      proliferative curve of the cultured cells were also investigated. RESULTS: The
      primary cells in culture are multiangular or irregular, and the confluent
      trabecular cells grow as a single cell layer. The junctions between trabecular
      cells observed most frequently are puncta adherens and gap junction. Trabecular
      cells showed apical villons projections and had a high density of various
      organelles. The trabecular cells were stained intensely with monoclone antibodies
      to fibronection and laminin and NSE. And it had negative reaction to monocolone
      antibodies to VIII factor. The cultured cells showed a longer doubling time.
      CONCLUSION: The culture of human trabecular cells in vitro was established. This
      was a key step to dissect the trabecular specimen accurately and carefully.
      According to the different cellular growth patterns and speed, morphologic and
      immunohistochemical characteristics from that of the near cells, the cultured
      human trabecular cells can been identified.

PMID- 9639850
TI  - [Changes of the cornea induced by lipopolysaccharide in Lewis rats].
AB  - PURPOSE: To investigate changes of the cornea induced by lipopolysaccharide
      (LPS). METHODS: Immunohistochemical study using monoclonal antibodies to
      monocytes, macrophages (ED1, ED2) and MHC class II antigen (OX6) was performed on
      the corneal wholemounts obtained from normal lewis rats and those after LPS
      injection. RESULTS: Macrophages were noted to be present in whole cornea with a
      gradually decreased cell density from limbus to central part in normal lewis
      rats. However, major histocompatibility complex class II antigen (MHC class II)
      positive cells were only distributed at limbus. Footpad injection of LPS induced
      an increase of monocytes and macrophages in whole cornea and a dramatical changes
      of these cells morphologically. MHC class II-positive cells were only and shortly
      noted on the surface of the cornea endothelium at early stage after LPS
      injection. CONCLUSION: LPS-induced increase of macrophages in the cornea may be
      an important defense mechanism in response to LPS challenge. On the other hand,
      the absence of MHC class II-positive cells both in the normal and in the inflamed
      cornea may be contributed to the stability of immunological microenvironment
      within this tissue.

PMID- 9639851
TI  - [The effect of mitomycin C on activities of carbonic anhydrase and ATPase of the
      ciliary body epithelium in rabbit].
AB  - PURPOSE: Enzymohistochemical methods were performed to observe the effect of
      mitomycin C(MMC) on the activities of carbonic anhydrase (CA) and ATPase of the
      ciliary body epithelium in rabbits after using 0.2mg/ml mitomycin C during
      sclerectomy for the further study on the mechanism of the decrease of intraocular
      pressure postoperatively. METHODS: 0.2mg/ml mitomycin C was topically applicated
      during the sclerectomy in rabbit eyes. 7 days postoperatively, Hasson's method
      and plumbum nitrate's method were used to stain the CA and ATPase of the ciliary
      body epithelium. The grey value of the enzymes was quantitated by Image Analysor.
      RESULTS: MMC inhibited the activities of CA and ATPase of the ciliary body
      epithelium underlying the site of MMC application, but the difference of
      enzymatic activities of the region 90 degree apart from the surgical site and
      that of surgical site in normal saline control group was not statistically
      obvious (P < 0.05). CONCLUSIONS: MMC could inhibit the activities of CA and
      ATPase of ciliary body epithelium, thus leading to the decreased secretion of
      humor aqueous and the lowerdown of intraocular pressure even persistent hypotony.

PMID- 9639852
TI  - [The approach of cloned method in a human retinoblastoma cell line SO-Rb50].
AB  - PURPOSE: In order to obtain the same characteristic tumor cells in genetical and
      biological aspect, the cloned human retinoblastoma cell line SO-Rb50 established
      in our department is reported in this paper. METHOD: SO-Rb50 cells were cloned in
      multi-well plates. RESULT: Non-rosette Rb cells were successfully cloned while
      rosette Rb cells failed. CONCLUSION: The result suggested that high
      differentiated Rb cells were difficult to be cloned.

PMID- 9639853
TI  - [Assessment of the toxicity of TAH on the cell lines of SO-Rb50 and SO-Rb70].
AB  - PURPOSE: MTT assay was evaluated on cytoxicity for suspension growing cell lines
      of SO-Rb50 and SO-Rb70, and the toxicity of TAH (the total alkaloid of peqanum
      harmala L) on the above cell lines was assessed. METHODS: The relationships
      between cell number and optical density, between optical density and exposure
      time of MTT, and the stability of formazan crystal solution in MDSO were
      determined. And the toxicity of TAH on the cell lines of SO-Rb50 and SO-Rb70 in
      vitro with MTT assay was assessed. RESULTS: There was a direct proportional
      relationship between the amount of cell number and its optical density; The
      optical density increased gradully within 12 hours of the MTT incubation time;
      The stable time of the formazan crystal solved in DMSO was 11 hours. The IC50
      values (micrograms/ml) of TAH on SO-Rb50 were 10.66, 4.82 respectively for 48 and
      72 hours; and on SO-Rb70 were 6.38, 4.2 respectively for 48 and 72 hours.
      CONCLUSION: MTT assay can be used for suspension growing cell lines of SO-Rb50
      and SO-Rb70: TAH has obvious toxicity to these two cell lines.

PMID- 9639854
TI  - [The evaluation of oscillatory potentials of the electroretinogram in the early
      diagnosis of the patients with primary open angle glaucoma].
AB  - PURPOSE: To study the changes in the oscillatory potentials (OPs) of the
      electroretinogram in the earlier or early stage of primary open angle glaucoma.
      METHODS: OPs were recorded in thirty-three normal subjects (66 eyes) and 30
      patients with primary open angle glaucoma (POAG) (58 eyes). The abnormal rates of
      OPs in the different stages of POAG were analyzed and the sensitivity and the
      specificity of OPs were also determined. RESULTS: The overall OPs amplitudes
      (sigma o) were reduced in the patients with POAG and the amounts of small
      wavelets were also decreased. The total abnormal rate of sigma o was 67.24%, and
      42.86% in the earlier stage, 65.38% in the early stage and 76.00% in the advanced
      and late stage. The sensitivity and the specificity of OPs were 67.24% and
      92.42%. OPs had correlation with C/D. CONCLUSION: OPs can be considered as an
      indicator of earlier or early diagnosis of patients with POAG before visual field
      loss is detected.

PMID- 9639855
TI  - [The study of local electroretinogram in age-related macular degeneration].
AB  - PURPOSE: Observing the features of electro-activities at macular region in age
      related macular degeneration (AMD), and evaluating the sensitivities of local
      electroretinogram (LERG). METHODS: The LERG of 2.5, 5, 7.5 degrees at macula had
      been recorded in 99 eyes (68 dry form, 31 wet form) of 80 AMD patients. The
      contrast study had also been carried out with visual acuities and lesion areas at
      the corresponding region. RESULTS: The results showed that there were no
      significant differences between the decreased amplitudes of a and b waves of LERG
      in dry form AMD with normal controls (P > 0. 05). While significant differences
      existed in wet form AMD (P < 0.01). The changes of LERG at 2.5 degrees were
      greater than those of the other two regions. The correlation study on b wave
      amplitude and visual acuity of AMD patients showed that there was a positive
      correlation existed between them only in wet form AMD at 2.5 degrees region (r =
      0.516, P < 0.05). The negative correlations were observed between amplitudes of b
      wave and lesion areas in wet form AMD at the three macular regions. Drusen of dry
      form AMD had no effects on the amplitudes of LERG. CONCLUSIONS: The impairments
      on macular function from two types of AMD are different. This study reveals that
      the LERG is a sensitive method of visual electrophysiology for measuring macular
      function. The smaller the testing area, the higher the sensitivity.

PMID- 9639856
TI  - [Evaluation for grading standard of oblique flashlight test].
AB  - PURPOSE: We try to study the validity and reliability of grading standard of
      oblique flashlight test in this paper. METHODS: The validity of the grading
      standard of the oblique flashlight test was evaluated in 251 eyes. Based on
      anterior chamber angle as the gold standard, different grades of oblique
      flashlight test can find capable of closure angle sensitivity and specificity.
      The reliabilities (interobserver agreement and intraobserver agreement) also were
      evaluated in 250 and 88 eyes. RESULTS: 1. Validity of grading standard of oblique
      flashlight test: the results showed that it can find capable of closure angle
      sensitivity is 96.67%, specificity is 74.53% and Youden's index is 0.712, when
      the grades cutoff point on grade II. 2. Reliability of grading standard of
      oblique flashlight test: the results showed that the intraobserver agreement was
      observed agreement (Po) = 0.8, Kappa value (K) = 0.74 , Z = 22.48 and the
      intraobserver agreement was Po = 0.909, K = 0.875, Z = 16.08. CONCLUSIONS: The
      results of this research showed there are satisfactory validity and reliability
      for grading standard of oblique flashlight test. The test may be applied widely
      to estimate shallow anterior chamber and narrow angle.

PMID- 9639857
TI  - [The comparative study of the macular light threshold in the normal and low
      visual acuity people].
AB  - PURPOSE: To test the macular light threshold (MLT) and the change of macular
      light sensitivity (MLS) in the normal and low visual acuity people. METHODS: MLT
      of 93 eyes of the normal and 76 eyes of low visual acuity people was measured
      with macular threshold test of Humphrey Field Analyzer-640. RESULTS: 1. MLT
      increases with age, there is a negative correlation between MLS and age 2. MLT of
      low visual acuity people is significantly higher than that of the normal visual
      acuity people in the same age group; 3. No significant difference of MLT was
      found in the four quadrants of visual field in the same age group; 4. No
      significant difference of MLT was found between male and female. CONCLUSIONS: MLS
      of the normal visual acuity people is superior to that of the low visual acuity
      people; MLS decreases with age.

PMID- 9639858
TI  - [Effect of combining EGF with KGF on proliferation of human corneal epithelial
      cells].
AB  - OBJECTIVE: To select effective drugs for enhancing corneal epithelial wound
      healing and treating persistent corneal epithelial defect. METHODS: Epidermal
      growth factor (EGF) and keratinocyte growth factor (KGF) were added to cultures
      of human corneal epithelial cells and DNA synthesis in corneal epithelial cells
      were measured with [3H]-thymidine incorporation and liquid scintillation
      techniques. The cells were counted in a hemocytometer to determine the doubling
      time. RESULTS: 10 ng/ml EGF, 10 ng/ml KGF enhanced cellular proliferation
      effectively (P < 0.01). EGF in combination with KGF, the enhancement was more
      effective (P < 0.05) and reduced the doubling time. CONCLUSIONS: Our results
      suggest that exogenous EGF with KGF can stimulate proliferation of human corneal
      epithelial cells and it may be of potential use clinically for treatment of
      persistent corneal epithelial

PMID- 9639859
TI  - [Surgical treatment for congenital motive defect nystagmus by the parks (5, 6, 7,
      8mm) procedure or the augmented Parks procedure].
AB  - PURPOSE: The purpose of the surgical treatment for patients with congenital
      motive detect nystagmus was to correct deviation of the eye and the head tilt, to
      improve vision and eliminate nystagmus. METHODS: 19 patients underwent the Parks
      (5, 6, 7, 8mm) or the augmented Parks procedure from 1987 to 1994. For patients
      with abnormal head turn > or = 30 degrees, We used a 40-60% augmented Parks
      procedure. RESULTS: A follow up of 19 patients ofr an average of 22 months
      revealed a marked improvemtnts. After operation, the head turn was decreased form
      30.5 degrees to 4.9 degrees, the intensity of nystagmus was decreased from 36.0
      to 9.7, 21 eyes (55.3%) of 19 patients improved by two or more lines of Snellen
      visual acuity. CONCLUSIONS: The Parks (5, 6, 7, 8mm) and the augmented Parks (5,
      6, 7, 8mm) procedure produce a marked correction for congenital motive defect
      nystagmus.

PMID- 9639860
TI  - [A report of congenital giant defects in macular and choroid of both eyes].

PMID- 9639861
TI  - 'Inclined abstainers': a problem for predicting health-related behaviour.
AB  - A longitudinal test of the association between motivation to undertake a
      precautionary health action and subsequent behaviour was conducted on women's
      uptake of the cervical screening test. A sample of never-screened women (N = 166)
      completed measures derived from protection-motivation theory (PMT; Rogers, 1983).
      One year later, screening uptake was reliably determined from medical records.
      While regression analyses demonstrated that PMT variables predicted both
      motivation to undergo cervical screening and screening uptake, there was,
      nonetheless, a good deal of inconsistency between protection motivation and
      screening behaviour. Fifty-seven per cent of those who indicated they were
      willing to undergo the test did not do so within a one-year period. Discriminant
      analysis was therefore used to test the ability of cognitions specified by PMT to
      distinguish four patterns of association between motivation and behaviour:
      inclined actors, inclined abstainers, disinclined actors and disinclined
      abstainers. While PMT variables could successfully classify the four groups, it
      was not possible to derive a reliable discriminant function which distinguished
      between inclined actors and inclined abstainers. The results suggest that PMT
      provides a useful account of choice motivation but does not address the
      psychological processes by which intention is translated into action. Recent
      calls for the development of a social psychology of volition are discussed in the
      light of these findings.

PMID- 9639862
TI  - Thinking about one's gender group's privileges or disadvantages: consequences for
      well-being in women and men.
AB  - Thoughts about group-based privileges or disadvantages were expected to have
      different consequences for personal and group well-being, depending on whether
      the individual is a member of a high- or low-status group. To test this
      hypothesis, women and men were randomly assigned to consider the ways that their
      gender group membership has resulted in either beneficial or detrimental outcomes
      in their lives. For men, thinking about their gender group's privileges resulted
      in lower scores on the group-related well-being measures compared to women, and
      thinking about their group's disadvantages resulted in higher personal self
      esteem scores in men compared to women. It is suggested that among high-status
      group members, thinking about privilege can evoke guilt and taint one's group
      image, whereas thinking about disadvantage can augment personal internal
      attributions for the positive outcomes received. Discussion focuses on the
      implications that the operation of two types of mechanisms--group-based emotions
      and the undermining or augmenting of attributions--has for the responses of high-
      and low-status group members when their groups are portrayed as exerting either
      negative or positive effects on their lives.

PMID- 9639863
TI  - Are men more competitive than women?
AB  - This study uses competition diaries to see whether women and men differ in (a)
      what they compete over, (b) whom they compete with, and (c) their competitive
      tactics, including use of aggression. In Study 1, university students kept
      diaries of their competitive interactions during the term. Sex differences, few
      overall, were as follows: (a) men's diaries contained more same-sex competition,
      (b) women competed more about looking attractive whereas men competed more about
      sports, and (c) men used physical (but not verbal) aggression more frequently
      than women. In Study 2 strength of competition was also measured by
      questionnaire. Women and men felt equally competitive overall, but men felt more
      competitive about athletics and sexual attention whereas women felt more
      competitive about looking attractive. In men, but not women, competitiveness for
      financial success was correlated with various aspects of mating competition.
      Young men were more competitive than older men in a variety of domains and were
      also more physically and verbally aggressive, but no age difference in aggression
      was found for women.

PMID- 9639864
TI  - Do intentions predict condom use? Meta-analysis and examination of six moderator
      variables.
AB  - This study used meta-analysis to quantify the relationship between intentions and
      behaviour in prospective studies of condom use. The effects of six moderator
      variables were also examined: sexual orientation, gender, sample age, time
      interval, intention versus expectation and condom use with 'steady' versus
      'casual' partners. Literature searches revealed 28 hypotheses based on a total
      sample of 2532 which could be included in the review. Overall, there was a medium
      to strong sample-weighted average correlation between intentions and condom use
      (r+ = .44), and this correlation was similar to the effect sizes obtained in
      previous reviews. There were too few studies of gay men to permit meaningful
      comparison of effect sizes between homosexual versus heterosexual samples. Gender
      and measurement of intention did not moderate the intention-behaviour
      relationship. However, shorter time intervals, older samples and condom use with
      'steady' rather than 'casual' partners were each associated with stronger
      correlations between intentions and condom use. Factors which might explain the
      significant effects of moderator variables are discussed and implications of the
      study for future research on intention-behaviour consistency are outlined.

PMID- 9639865
TI  - A new class of cis-monobactam derivatives bearing a sulfamoyloxymethyl or an N
      alkylsulfamoyloxymethyl group at position 4: synthesis and antibacterial
      activity.
AB  - A new series of monobactam derivatives, bearing unsubstituted or N
      monosubstituted sulfamoyloxymethyl groups in position 4 was synthesized either in
      racemic or in optically active form. Their in vitro antibacterial activity was
      tested in comparison with carumonam 1a and its methoxyimino derivative 1b.

PMID- 9639866
TI  - 1-Aminocylopropane-1-carboxylic acid derivatives as ligands at the glycine
      binding site of the N-methyl-D-aspartate receptor.
AB  - Several 1-aminocyclopropane-1-carboxylic acid derivatives were prepared and
      tested for activity at the glycine-binding site of the N-methyl-D-aspartate
      (NMDA) receptor complex. Structural modifications involved the amino group, the
      carboxylic function or position 2 of the ring. When tested in a [3H]-MK-801
      binding assay in the presence of glutamic acid, some of the compounds were able
      to activate the receptor. Two of them (3e and 6) are selective ligands for the
      glycine site of the NMDA receptor.

PMID- 9639867
TI  - Synthesis and A1 and A2A adenosine binding activity of some pyrano[2,3-c]pyrazol
      4-ones.
AB  - A series of pyrano[2,3-c]pyrazol-4-ones was synthesized and evaluated for bovine
      brain adenosine A1 and A2A receptor binding affinity. Substituents at positions 5
      and/or 6 were varied in order to define the structure-activity relationships in
      these new kinds of adenosine receptor ligands. The most selective and potent
      ligand among the reported compounds was the 1,4-dihydro-1-phenyl-3-methyl-6-(3
      aminophenyl)-pyrano[2,3-c]pyraz ol-4-one 11 which showed a 27-fold selectivity
      for A1 receptor and a Ki value of 84 nM.

PMID- 9639868
TI  - Variations in rat biochemical parameters after buckshot implant.
AB  - Twenty eight albino Wistar rats were implanted with two 100 mg lead spheres: 14
      received the implant in the peritoneum (P) and 14 in the thigh (T). Variations in
      the activity of delta-aminolevulinic dehydratase (ALAD), of urinary delta
      aminolevulinic acid (ALAU), of hematoporphyrins (HP) and of lead blood levels
      (BPb) were then determined at 30, 60 and 90 days with respect to basal values.
      Parallel determinations were performed by the same schedule in 7 rats implanted
      with two glass beads and in 8 sham animals receiving surgical incision alone.
      Techniques employed for ALAD were Berlin and Schaller; for ALAU, Tomokuni and
      Ogata; for HP, Piomelli; and for BPb, atomic absorption spectrophotometry. As
      indicators of lead presence, HP and ALAU proved better, both in P and in T rats.
      The replacement of lead buckshot for small game hunting by other less toxic
      elements is recommended.

PMID- 9639869
TI  - Synthesis, antimicrobial activity and bleaching effect of some reaction products
      of 4-oxo-4H-benzopyran-3-carboxaldehydes with aminobenzothiazoles and hydrazides.
AB  - The synthesis of the biologically active novel systems derived from reaction of 3
      formylchromones with three types of amino derivatives, 6-R2-2
      aminobenzothiazoles, 6-amino-2-R3-thiobenzothiazoles and hydrazide derivatives
      (derived from cyanoacetic, isonicotine, salicylic and gallic acids) was carried
      out. The structures of the prepared compounds have been proved by elemental
      analysis, 1H NMR and IR spectra. Antimicrobial activity was studied against the
      following microorganisms--bacteria G+ (Staphylococcus aureus 29/58, Bacillus
      subtilis 18/66), G- (Escherichia coli 326/71, Pseudomonas aeruginosa); yeasts:
      Candida albicans, Saccharomyces cerevisiae; moulds: Microsporum gypseum,
      Aspergillus niger, Scopulariopsis brevicaulis; and against typical and atypical
      mycobacteria: Mycobacterium tuberculosis (H37Rv), Mycobacterium kansasii (PFG 8),
      Mycobacterium avium (My 80/72), Mycobacterium fortuitum (1021). The hereditary
      bleaching effect on the plastid system of Euglena gracilis, a unique phenomenon
      of the biological activity of chromone derivatives, is reported. The bleaching
      test on E. gracilis is used for detecting extranuclear mutations.

PMID- 9639870
TI  - Synthesis of 1-methyl-4-(N-aroyl)-piperidinamides with anti-inflammatory and
      analgesic activities.
AB  - Two series of 1-methyl-4-(N-aroyl)-piperidinamides were synthesized and evaluated
      for their anti-inflammatory and analgesic properties, as well as for their
      gastrointestinal irritation liability. A non-aromatic derivative, 1-methyl-4-(N
      cyclohexanoyl)-piperidinamide, was synthesized and evaluated in order to obtain a
      more exhaustive knowledge of the structure-activity relationship.

PMID- 9639871
TI  - Synthesis and cytotoxic activity of N-substituted thiosemicarbazones of 3-(3,4
      methylenedioxy)phenylpropanal.
AB  - Five new N-substituted thiosemicarbazones of 3-(3,4-methylenedioxy)phenylpropanal
      were synthesized. Safrole, a natural product obtained from sassafras oil (Ocotea
      pretiosa), was oxidized to alcohol using BH3-THF and H2O2, followed by oxidation
      to aldehyde using pyridinium dichromate (PDC) and condensation with five N
      substituted derivatives of thiosemicarbazide. Tests were performed to evaluate
      the cytotoxic activity with continuous chain KB cells (epidermoide carcinoma of
      the floor of the mouth). Compounds 5 and 6 showed IC50 values of 1.5 and 4.6
      micrograms/ml, respectively.

PMID- 9639872
TI  - Synthesis and preliminary antileukemic studies of cyclic mitoguazone analogues.
AB  - Analogues of mitoguazone bearing a terminal amidino group as a part of the seven
      membered ring of 1,3-diazepine and six-membered ring of pyrimidine were prepared
      in order to evaluate in vivo antileukemic action towards L1210 leukemia in mice.
      Preliminary pharmacological screening showed that the investigated compounds
      increase the life span (T/C%) of the treated mice in comparison with the
      untreated animals. The strongest antineoplastic effect was exhibited by compound
      8.

PMID- 9639873
TI  - A hydrophobic peptide (VAP-peptide) of the silkworm, Bombyx mori: structure,
      expression and an enhancing function of diapause hormone activity.
AB  - We have recently identified a unique lipophilic peptide (VAP-peptide) with
      diapause egg inducing activity in the silkworm, Bombyx mori (Imai et al., 1996).
      The cloning and sequencing of cDNA encoding VAP-peptide have demonstrated that
      the deduced amino acid sequence consisted of 84 amino acid residues, from which
      the mature VAP-peptide of 68 amino acid residues was released by cleaving a
      signal sequence. Searches of the GenBank data base revealed no significant
      sequence similarity to other proteins including diapause hormone (DH). VAP
      peptide gene was selectively expressed just before and at adult eclosion in the
      head and the thorax not in the abdomen. By a Western blot analysis, VAP-peptide
      was also localized in the head and the thorax of adults. The purified recombinant
      VAP-peptide could not induce diapause eggs even when injected at a high dose of
      10 nmol/pupa. Whereas, injection of a mixture of VAP-peptide and DH clearly
      decreased a half-maximum dose (ED50 value) and a threshold dose (TD value) of DH,
      and these values decreased according to increasing molar ratios of VAP-peptide to
      DH. Thus, the VAP-peptide is concluded to be an endogenous protein acting as a
      potent enhancer of DH activity through interaction with DH.

PMID- 9639874
TI  - G0/G1 cell cycle arrest in the brain of Sarcophaga crassipalpis during pupal
      diapause and the expression pattern of the cell cycle regulator, proliferating
      cell nuclear antigen.
AB  - During pupal diapause in the flesh fly, Sarcophaga crassipalpis, the cells of the
      brain are arrested in the G0/G1 phase of the cell cycle. When diapause is
      terminated with a topical application of hexane, cell cycling is evident within
      12 hours. Four G1 and S phase regulatory genes were examined by Northern blot
      analysis to evaluate their expression patterns in relation to this cell cycle
      arrest. A distinction between diapausing and nondiapausing individuals was noted
      only for Proliferating Cell Nuclear Antigen (PCNA). PCNA was highly expressed
      after diapause was terminated but not during diapause. In contrast, cyclin E,
      p21, and p53 were expressed equally at all times. In situ hybridization using
      PCNA probes further indicated a correlation between PCNA transcription
      (expression) in the brain and cell cycling. Our evidence thus suggests a
      potential role for PCNA as an important regulator of cell cycle arrest during
      diapause.

PMID- 9639875
TI  - TER94, a Drosophila homolog of the membrane fusion protein CDC48/p97, is
      accumulated in nonproliferating cells: in the reproductive organs and in the
      brain of the imago.
AB  - We have cloned a Drosophila homolog of the membrane fusion protein CDC48/p97. The
      open reading frame of the Drosophila homolog encodes an 801 amino acid long
      protein (TER94), which shows high similarity to the known CDC48/p97 sequences.
      The chromosomal position of TER94 is 46 C/D. TER94 is expressed in embryo, in
      pupae and in imago, but is suppressed in larva. In the imago, the
      immunoreactivity was exclusively present in the head and in the gonads of both
      sexes. In the head the most striking staining was observed in the entire neuropil
      of the mushroom body and in the antennal glomeruli. Besides TER94, sex-specific
      forms were also detected in the gonads of the imago: p47 in the ovaries and p98
      in the testis. TER94/p47 staining was observed in the nurse cells and often in
      the oocytes, while TER94/p98 staining was present in the sperm bundles. On the
      basis of its distribution we suggest that TER94 functions in the protein
      transport utilizing endoplasmic reticulum and Golgi derived vesicles.

PMID- 9639876
TI  - cDNA and deduced amino acid sequences of a peritrophic membrane glycoprotein,
      'peritrophin-48', from the larvae of Lucilia cuprina.
AB  - The gut of most insects is lined with a semi-permeable peritrophic membrane (or
      peritrophic matrix) composed of chitin, proteoglycans and proteins. Despite the
      probable importance of the peritrophic membrane in facilitating the digestive
      process and protecting insects from invasion by micro-organisms and parasites,
      there has been little characterization of the specific components and their
      interactions within this acellular structure. Here we report the characterization
      of an integral peritrophic membrane glycoprotein, peritrophin-48, from the larvae
      of the fly Lucilia cuprina, a primary agent of cutaneous myiasis in sheep.
      Peritrophin-48 was purified from peritrophic membrane obtained by larval culture
      and its location within the peritrophic membrane determined by immuno
      fluorescence and immuno-gold localizations. The cDNA coding for peritrophin-48
      was cloned and sequenced. The deduced amino acid sequence codes for a protein of
      375 amino acids containing an amino-terminal signal sequence followed by five
      similar, but non-identical domains, each approximately 65-70 amino acids in
      length and characterised by a specific register of six cysteines. The deduced
      amino acid sequence shows significant similarity to two other peritrophic
      membrane proteins, peritrophin-95 and peritrophin-44, from the same species. A
      reverse transcriptase-PCR approach indicated that there are several highly
      related peritrophin-48 genes expressed in each individual. Reverse transcriptase
      PCR also demonstrated the expression of peritrophin-48 in all three larval
      instars and adults but not pupae or eggs. Peritrophin-48 was expressed only by
      the cardia and by the larval midgut. A simple structural model of a basic unit of
      a type 2 peritrophic membrane is presented.

PMID- 9639877
TI  - Characterization of two male-specific polypeptides in the tergal glands
      secretions of the cockroach Leucophaea maderae (Dictyoptera, Blaberidae).
AB  - During the sexual behavior of cockroaches, the female mounts the courting male to
      feed on the proteinaceous secretion of the tergal glands. Polyacrylamide gel
      electrophoresis of male and female protein extracts after cuticle wiping revealed
      three major bands. Two of 18 and 22 kDa, named Lma-P18 and Lma-P22, are specific
      to the male tergal extracts. Moreover, Lma-P22 is only found in the male second
      tergite extracts. The third one of 54 kDa, named Lma-P54, is common to male and
      female extracts and could be considered as an ubiquitous surface protein. Several
      other minor proteins are also present on the body surface of adults of both
      sexes. Quantitation of the total protein amount of the male tergal gland
      secretion shows a progressive accumulation from adult ecdysis to sexual maturity.
      Western blot analysis using antibodies raised against Lma-P22 and Lma-P54
      confirms that Lma-P22 is only secreted by the male second tergite glands.
      Immunohistolocalization demonstrates that these three major proteins are produced
      by class 3 glandular cells.

PMID- 9639878
TI  - Micropellicular stationary phases for high-performance liquid chromatography of
      double-stranded DNA.
AB  - The central role of nucleic acids in biosciences has effectuated the rapid
      development of numerous techniques for their isolation, separation,
      characterization and quantitation. Advances in high-performance liquid
      chromatography, particularly the introduction of novel microparticulate sorbents,
      have greatly promoted the separation and quantitation of nucleic acids. Because
      of their favorable mass transfer properties, micropellicular packing materials
      are advantageous for fast and high-resolution separations of double-stranded (ds)
      DNA molecules. With micropellicular packings, anion-exchange and ion-pair
      reversed-phase chromatography are the most popular chromatographic separation
      modes for dsDNA. The effective separation mechanisms in both chromatographic
      techniques are preferably described by nonstoichiometric models, that are founded
      on a better physicochemical background than traditional stoichiometric models.
      Column efficiency, retention characteristics, and size or sequence dependency of
      retention of dsDNA are greatly influenced by the chosen operational variables in
      both chromatographic modes. The applicability of HPLC with micropellicular
      stationary phases nucleic acids research includes preparative DNA fractionation,
      DNA restriction mapping, analysis of polymerase chain reaction products and
      purification of plasmid DNA.

PMID- 9639879
TI  - Preparative purification of supercoiled plasmid DNA using anion-exchange
      chromatography.
AB  - Large scale manufacturing of gene vectors such as plasmid DNA is an important
      issue in gene therapy. Anion-exchange chromatography is fundamental in the
      downstream processing of plasmids both as a process and analytical technique.
      This work reports the use of Q-Sepharose columns (1, 10 and 40 ml) for the
      preparative purification of plasmid pUC18. NaCl gradient elution enabled the
      isolation of supercoiled plasmid from low-M(r) RNA, cDNA and plasmid variants. A
      compact covalently closed, supercoiled form of denatured plasmid carrying large
      stretches of single-stranded DNA was identified as one of the major contaminants.
      Anion-exchange HPLC on a Poros QE 20 column was used to quantify plasmid yield.
      Supercoiled plasmid was recovered in a single fraction with a 62 +/- 8% yield.
      Loadings higher than 40 micrograms/ml gel could be used but at the expense of a
      loss of resolution between open circular and supercoiled forms. Plasmid quality
      was evaluated by gel electrophoresis, restriction analysis, transformation
      experiments and protein assays.

PMID- 9639880
TI  - Quantitative analysis of gene expression by ion-pair high-performance liquid
      chromatography.
AB  - We have analyzed the utility of ion-pair reversed-phase HPLC for gene
      quantification by competitive reverse transcriptase polymerase chain reaction (RT
      PCR). Competitive RT-PCR reactions employed various RNA competitors which shared
      high sequence similarity to the native transcripts for which they served as
      references. Competitive reactions resulted in the detection of two reaction
      products when reactions were analyzed by agarose gel electrophoresis, but three
      products when analyzed by HPLC. The third product was demonstrated to be a
      heteroduplex formed between mixed strands of native and competitor amplicons.
      Mathematical analysis of these competitive reactions indicated that
      identification and quantification of the heteroduplexes were essential to produce
      accurate gene quantification. PCR amplification efficiency was shown to be
      identical for native and competitor transcripts. However, RT efficiency
      differences were observed which may be sequence dependent. These differences were
      highly consistent across reactions for the same native and competitor inputs.
      Increasing the sequence similarity resulted in a competitor which had the same RT
      efficiency as the native transcript. Titration of various levels of competitor
      against native RNA resulted in the expected linear relationships which had slopes
      of unity. Quantitation could be performed with similar precision in single tube
      comparisons in which the initial abundance of the native transcript was
      calculated by knowledge of the final reaction product ratio and the initial
      competitor input level. The assay system is highly accurate, i.e. the measured
      level of gene expression reflected the actual copy number of the gene present in
      the sample. This was demonstrated by performing reactions in which known amounts
      of native transcript were quantified and the amount estimated by the assay was
      shown to be the same as the known amount added to the reaction. A similar
      approach has been devised for examining the relative levels of alternatively
      spliced isoforms. In this system, primers were selected to produce reaction
      products which served as their own internal competitors (by spanning the
      alternative splice site). Hormonal dependence of the ratio of abundance of two
      isoforms of the rabbit RUSH-1 gene was demonstrated.

PMID- 9639881
TI  - Separation of oligonucleosomal DNA fragments from apoptotic animal cells using a
      triad of Sephacryl columns.
AB  - The degradation of DNA, resulting in information of oligonucleosomal fragments,
      is a characteristic feature of apoptosis, i.e., the process of programmed cell
      death. In this work we have developed a method for exact determination of the
      proportion of fragmented DNA in an apoptotic cell population. To this end we
      employed Sephacryl gel chromatography matrices and UV detection of DNA
      concentration. The disturbing effect of low-molecular-mass UV-absorbing
      contaminants was eliminated by insertion of a Sephacryl S-200 HR pre-column.
      Optimum resolution of DNA samples isolated from apoptotic cells was achieved
      using a triad of Sephacryl S-200 HR, Sephacryl S-500 HR and Sephacryl S-1000 SF
      columns.

PMID- 9639882
TI  - N-hydroxysuccinimide ester labeling 5'-aminoalkyl DNA oligomers: reaction
      conditions and purification.
AB  - Difficulties were encountered in labeling 5'-aminoalkyl DNA oligomers with
      glycolketo electrophore N-hydroxysuccinimide esters in aqueous sodium bicarbonate
      (a common base for this purpose), followed by C18-silica reversed-phase high
      performance liquid chromatography (HPLC) to achieve purification. The
      electrophore-labeled oligomers were not separated readily either from the
      hydrolyzed electrophore or from the starting oligomer. This problem was overcome
      by conducting the reaction with triethylamine as a base, organic washing the
      reaction mixtures after evaporation, and separating on a C18-poly(styrene
      divinylbenzene) HPLC packing.

PMID- 9639883
TI  - Analysis of clinically relevant, diagnostic DNA by capillary zone and double
      gradient gel slab electrophoresis.
AB  - A number of applications of capillary zone electrophoresis (CZE) in sieving
      liquid polymers (notably linear polyacrylamides and cellulose) for the analysis
      of polymerase chain reaction products of clinically relevant, diagnostic DNA, are
      reviewed here. The fields covered are human genetics, quantitative gene dosage,
      microbiology and virology, forensic medicine and therapeutic DNA (notably
      antisense nucleotides). Some unique, novel developments are highlighted, such as
      (a) non-isocratic CZE, i.e., temperature-programmed CZE for detection of DNA
      point mutations and (b) the synthesis of novel N-substituted acrylamides,
      offering extreme resistance to alkaline hydrolysis, coupled with high
      hydrophilicity. In the field of denaturing gradient gel electrophoresis (DGGE),
      as routinely performed in gel slabs, a novel methodology is described, i.e.,
      double-gradient DGGE. In this technique, two gradients are simultaneously applied
      along the migration direction; a chemical denaturing gradient, for partially
      unwinding homo- and hetero-duplexes of DNA and a porosity gradient, for re
      compacting diffuse bands melting over a broader range of denaturing conditions.
      Both the CZE and the slab gel methodologies, with the latest developments
      described in this review, appear to be promising tools for screening diagnostic
      DNA.

PMID- 9639885
TI  - Comparison of slab gel electrophoresis and capillary electrophoresis for the
      detection of the fluorescently labeled polymerase chain reaction products of
      short tandem repeat fragments.
AB  - The sizing capability of slab gel electrophoresis for short tandem repeat (STR)
      fragments was compared to the sizing capability of capillary electrophoresis
      (CE). Both systems used automated laser fluorescence detection to detect four
      fluorescent dyes, enabling the use of an internal lane standard within each
      sample. The STR fragments were amplified using a multiplex polymerase chain
      reaction (PCR) in which the STR fragments Hum CD-4, Hum TH01, Hum D21S11 and Hum
      SE33 were amplified simultaneously. The reproducibility of the size calling was
      determined for both systems. The average standard deviation obtained for the slab
      gel system was 0.2, which was comparable to the standard deviation of 0.12
      obtained for the CE system. The CE system produced results comparable to those
      obtained on the slab gel system, with a level of precision of +/- 1.0 bp (between
      instruments).

PMID- 9639884
TI  - Contamination-free and automated composition of a reaction mixture for nucleic
      acid amplification using a capillary electrophoresis apparatus.
AB  - The acceptance of the polymerase chain reaction (PCR) as an amplification method
      in molecular diagnostics and the rapid development of capillary electrophoresis
      (CE) as an analysis method of those PCR products was a reason for us to
      investigate further integration of those two techniques. Using a fused-silica
      capillary as a pipette we were able to compose a PCR mixture in the CE apparatus.
      Because a capillary can be thoroughly rinsed and the CE apparatus is a closed
      system, the risk of contamination and therefore the occurrence of false positive
      results is minimized. The fact that a CE system can be fully automated
      contributes to a more reproducible and standardized PCR composition protocol.

PMID- 9639886
TI  - Fast DNA separations using poly(ethylene oxide) in non-denaturing medium with
      temperature programming.
AB  - We demonstrated fast DNA separations in low viscosity entangled solutions with a
      temperature gradient in a non-denaturing separation medium. The separations were
      carried out in a solution of commercially available poly(ethylene oxide) (PEO) [1
      x Tris(hydroxymethyl)aminomethane borate buffer, without urea] with a temperature
      gradient of 2 degrees C/min. The performance was compared with that of a solution
      of PEO with urea at ambient temperature. We found that the former condition gives
      sufficient resolution for accurate base calling and that in general, it gave
      better separation for fragments larger than 450 base pairs (bp). Most
      importantly, the separation speed approaches 30 bp/min. In addition, we describe
      a simple yet reliable gel preparation protocol for such separations.

PMID- 9639887
TI  - Separation of pd(GC)12 from pd(AT)12 by free solution capillary electrophoresis.
AB  - The two synthetic self complementary oligonucleotides pd(AT)12 and pd(GC)12 were
      separated by free solution capillary electrophoresis (CZE) using simple borate
      buffers. The effects of pH (7.5-9) and the concentration of the buffer (0.03-0.35
      M) were investigated. Higher pH values and buffer concentrations led to better
      resolution and longer migration times, the pH having a more pronounced effect on
      the separation than the concentration of the buffer. It is proposed that the
      conformation and effective length of the oligonucleotides may have a role in
      their separation in free solution capillary electrophoresis.

PMID- 9639888
TI  - Detecting single base substitutions, mismatches and bulges in DNA by temperature
      gradient gel electrophoresis and related methods.
AB  - Temperature gradient gel electrophoresis (TGGE) and related methods can separate
      DNA fragments that differ by a single base pair or defect. This article describes
      the basic features of TGGE, and reviews the theoretical model of DNA unwinding
      and its ability to predict DNA mobility in a temperature gradient gel. Recent
      applications of TGGE and related methods that were directed at detecting point
      mutations, and evaluating the effects of single site defects are also reported.

PMID- 9639889
TI  - Comparison of DNA migrations in two clamped homogeneous electric field chambers
      of different sizes. Relation between sample thickness and electrophoresis time.
AB  - We present here a method to compare the mathematical descriptions of DNA
      migration per pulse as a function of pulse time. It is based on obtaining robust
      estimates and variances of DNA reorientation time, migration velocities during
      and after DNA reorientation; and on the statistical comparisons of these
      estimates. We demonstrated an equal description for the migration per pulse of
      each DNA molecule separated under identical conditions in clamped homogeneous
      electric field (CHEF) and miniCHEF chambers. However, miniCHEF resolved the
      patterns in shorter times, because it uses thinner samples. The relationship
      between sample thickness and CHEF run time is also presented.

PMID- 9639890
TI  - Detection of gene expression in single neurons by patch-clamp and single-cell
      reverse transcriptase polymerase chain reaction.
AB  - Detection and quantitation of gene expression in single cells is especially
      important in the central nervous system where, at the cellular level, the synapse
      can be considered the single functional unit. For example, the consolidation of
      long-term memories may be mediated by persistent changes in the strength of
      synaptic transmission at individual synapses. In order to investigate the
      requirement for de novo RNA synthesis during long-term potentiation in individual
      neurons, we have combined single-cell electrophysiology with single-cell gene
      expression methodology. Described are methods combining whole-cell patch-clamp
      and single-cell RT-PCR for the detection of a single mRNA species for nitric
      oxide synthase, or, through a multiplex strategy, for the simultaneous detection
      of several mRNAs including heme oxygenase 2, protein phosphatase inhibitor 1
      protein, and several isoforms of the calcium/calmodulin dependent protein kinase
      II.

PMID- 9639891
TI  - High resolution free chromatin/DNA fiber fluorescent in situ hybridization.
AB  - High resolution chromatin/DNA fiber fluorescent in situ hybridisation (FISH) is a
      powerful system for physical mapping and genome research. With direct
      visualisation of molecular probes along released chromatin or DNA fiber, fiber
      FISH has become the method of choice to order genes or DNA markers within
      chromosomal regions of interest. Combined with DNA-protein in situ codetection
      fiber FISH shall play a more important role for analysis of genome function. In
      this paper the concept and technical developments of fiber FISH are reviewed with
      the emphasis of comparison on the various protocols. Future challenges are also
      discussed along with the highlights of the successful applications achieved by
      fiber FISH methodology.

PMID- 9639892
TI  - Development of guanine analyzer to measure activity of guanylate cyclase.
AB  - A previous analyzer of adenine compounds by high-performance liquid
      chromatography was converted for the determination of guanine, its nucleoside and
      nucleotides by a post-column fluorescence derivatization with phenylglyoxal (PGO)
      in place of bromoacetoaldehyde. The gel filtration column (Asahipak GS-320H) was
      used for separation by a mobile phase consisting of 25 mM sodium citrate buffered
      (pH 4.0)-150 mM NaCl solution and CH3CN (85:15, v/v) containing 15 mM PGO. The
      separated analytes reacted with flow through PGO in a reaction coil at 90 degrees
      C into fluorescent derivatives. Those derivatives were detected fluorimetrically,
      highly selective and quantitatively. The activity of soluble guanylate cyclase
      (sGC) in the neuroblastoma N1E-115 cell was measured by tracing the peak height
      of cGMP synthesized from substrate GTP using this guanine analyzer. The
      sensitivity of the present method was lower than the radioisotope method.
      However, our modified method was simpler, safer and quicker than the radioisotope
      method. Furthermore, this method could trace other guanine compounds
      simultaneously, allowing measurement of guanine metabolizing enzymatic activity.
      Therefore, it will be useful for screening of effectors on sGC.

PMID- 9639894
TI  - Temperature dependent population growth of Gyrodactylus derjavini on rainbow
      trout, Oncorhynchus mykiss.
AB  - Rainbow trout were experimentally infected with the ectoparasitic monogenean
      Gyrodactylus derjavini at three temperatures, 5.5 degrees C, 11.6 degrees C and
      18.7 degrees C. Subsequently, the infection level was monitored during the
      following 6 weeks. The population growth was positively correlated with
      temperature in the initial part of the investigation. At 18.7 degrees C growth of
      the parasite population was fast reaching a peak abundance within 3 weeks,
      whereafter the infection level decreased significantly. Peak abundance was
      recorded in week 5 at 11.6 degrees C. A very slow but steady parasite
      reproduction was noted at 5.5 degrees C, but no peak abundance was reached within
      6 weeks. The decline in parasite population after reaching peak levels is likely
      to be caused by a host response. The host response is also indicated by the
      parasites' active selection of particular microhabitats. This anti-monogenean
      response developed fastest at 18.7 degrees C, more slowly at 11.6 degrees C and
      was not recorded within 6 weeks at 5.5 degrees C.

PMID- 9639893
TI  - Analysis of T cell populations and IL-3 mRNA expression in mesenteric lymph node
      cells and intestinal intraepithelial lymphocytes in Strongyloides ratti-infected
      mice.
AB  - T cell populations and IL-3 mRNA expression were analysed in mesenteric lymph
      node cells and intestinal intraepithelial lymphocytes (IEL) in Strongyloides
      ratti-infected mice. On days 7 and 12 post-infection, 2.6 times as many
      mesenteric lymph node cells were present in S. ratti-infected mice compared with
      uninfected mice. Although the percentages of CD3+, CD4+ and CD8+ cells decreased
      during infection, the absolute numbers of these cell types increased on day 7 due
      to an overall increase in the mesenteric lymph node cell number. The CD4/CD8
      ratio in IEL was increased on day 5, whereas no significant change in the CD4/CD8
      ratio was observed in the mesenteric lymph node cells. Expression of IL-3 mRNA,
      which is an important cytokine for the induction of murine mucosal mastocytosis
      and S. ratti-expulsion, was examined in mesenteric lymph nodes and IEL of
      uninfected and infected mice. IL-3 mRNA was detected in mesenteric lymph nodes of
      S. ratti-infected mice but not detected in the lymph nodes of uninfected mice. IL
      3 mRNA was detected in IEL from both infected and uninfected mice with an 20-fold
      increase in expression in IEL of infected mice. Overall, IL-3 mRNA levels were
      higher in IEL than in mesenteric lymph nodes following S. ratti-infection.
      Expression of IL-4, IL-10, stem cell factor (SCF or c-kit ligand) and IFN-gamma
      mRNA was also examined in these two tissues. IL-10 mRNA was not detected in any
      tissue examined and IFN-gamma mRNA levels were unaltered as a result of an S.
      ratti-infection. Elevated expression of mRNA for SCF (5-fold) and IL-4 (20-fold)
      was observed in the mesenteric lymph nodes of infected mice. In contrast, SCF
      mRNA levels were similar in IEL of uninfected and infected animals and only a
      modest increase in IL-4 mRNA was observed in IEL of infected mice.

PMID- 9639895
TI  - Gastrointestinal and pulmonary nematode infections decrease goat productivity in
      Moroccan semi-arid conditions.
AB  - A herd of goats naturally infected with lungworm and gastrointestinal nematodes
      was divided into three groups and treated with either morantel tartrate or
      fenbendazole at strategic periods, i.e. in June (at pre-mating), in November (at
      pre-kidding) and in January (at early lactation) or left untreated. Morantel
      tartrate treatment (8 mg kg-1) was efficient in reducing the gastrointestinal
      nematode egg output and fenbendazole treatment (15 mg kg-1) was efficient in
      reducing the gastrointestinal nematode egg and small lungworm larvae faecal
      output. Reductions in mortality of adult goats and their progeny and improvement
      of rearing percentages were recorded in both treated groups, with fenbendazole
      showing a greater response than morantel tartrate. A relative risk analysis
      showed that mortality in goats and kids was significantly reduced in treated kids
      and goats. Reduction of 6.6% in kidding rates, 0.21 in prolificacy, and an
      increase of 1.3 in abortion rates, 8.3% in kid and 2.2% in goat mortalities,
      could be attributable to the small lungworm infection. Small lungworm infections
      seem therefore to be one of the main causes of indirect kid mortality and
      inadequate breeding performance of goats in the semi-arid Middle Atlas region of
      Morocco.

PMID- 9639896
TI  - Dung-derived biological agents associated with reduced numbers of infective
      larvae of equine strongyles in faecal cultures.
AB  - Two sets of dung-derived organisms from soil routinely fertilized with manure
      (MA) and soil chemically fertilized (CH) were cultured separately in the
      laboratory. Baermannized organisms from these cultures were added to 20 g of
      faeces from strongyle-infected horses to form three treatment groups: (i) no soil
      organisms; (ii) low inoculum of soil organisms containing all organisms present
      in a suspension of approximately 100 adult female free-living nematodes; and
      (iii) high inoculum containing those soil organisms present with approximately
      1000 adult female free-living nematodes. Three studies were conducted using MA
      cultures and faeces containing 50 stronglye epg, CH cultures and faeces
      containing 1500 strongyle epg, and a mixture of soil organisms from the two
      cultures (MC) and faeces containing 600 strongyle epg. Within each study, five
      control cultures and 15 each of low and high inoculum cultures were prepared and
      incubated at 24 degrees C and 95% humidity in a climate chamber for 15 days.
      Parasitic and free-living nematodes were then recovered by the Baermann technique
      and counted. The numbers of third stage larvae were significantly lower in the
      high inoculum group compared to controls. The percent reductions in the number of
      third stage larvae for the low and high inoculum groups were 63.6% and 90.9%,
      85.1% and 97.1%, 84.5% and 98.4% for MA, CH, and MC studies, respectively,
      indicating that mortality increased with the number of soil organisms added to
      cultures. Examination of the source cultures detected the presence of two species
      of nematophagous fungi and three genera of free-living nematodes reported to be
      predacious.

PMID- 9639897
TI  - Prevalence of cystic echinococcosis in camels (Camelus dromedarius) in Libya.
AB  - In an abattoir study, 514 camels, slaughtered for meat production in different
      areas of northern Libya were examined for the presence of cystic echinococcosis
      (CE). In addition, 367 sheep and 184 goats were examined. The overall prevalence
      of infection with CE was 48% in camels, 15.8% in sheep and 3.8% in goats. The
      infection rate, number and size of cysts were significantly higher in older
      camels. In six city abattoirs across northern Libya, i.e. Zawia, Tripoli, El
      Khumes, Mesurata, Sirt and Benghazi, the prevalence rate of infection in camels
      ranged from 38.7% to 55.2%, in comparison with sheep and goat rates which were
      between 0% and 37.9% and 0% and 8.2%, respectively. In camels, the lungs were the
      most frequently infected organs (85.4%) with liver cysts occurring at a
      significantly lower rate (33%). In contrast, the liver was the predominant
      infected site with prevalence values of 86% and 100% in sheep and goats,
      respectively. More than 90% of camel hydatid cysts were fertile. The possible
      role of camels in the transmission of CE in Libya is discussed.

PMID- 9639898
TI  - Histopathology of Sanguinicola inermis infection in carp, Cyprinus carpio.
AB  - The histopathological response of carp to Sanguinicola inermis was investigated
      by serial sectioning laboratory infected fish up to 90 days post infection (d
      p.i.). Juvenile flukes and adults caused mechanical damage to tissues during
      invasion and migration up to 28 d p.i. Adults partially occluded blood vessels
      and may have reduced blood circulation. In the initial phase of egg production
      (28-42 d p.i.), eggs and emigrating miracidia in gill tissue caused breakdown of
      vascular integrity, necrosis, hyperplasia, haemorrhage and eosinophilic
      infiltration of epithelial tissue. After 42 d p.i. the host granulomatous
      inflammatory response encapsulated eggs lodged in the gills, visceral sites and
      connective tissue displacing normal tissue. Encapsulation and subsequent
      degradation of eggs and miracidia within granulomata was highly developed by 90 d
      p.i. Laboratory infections of S. inermis can induce respiratory distress and
      therefore impair respiration of fish. The parasite also caused pathological
      changes in osmoregulatory, excretory and haemopoietic tissue and may impair
      function in these organ systems.

PMID- 9639899
TI  - Tests on the centrifugal flotation technique and its use in estimating the
      prevalence of Toxocara in soil samples from urban and suburban areas of Malaysia.
AB  - The influence of soil texture (silt, sand and laterite) and flotation solutions
      (saturated NaCl, sucrose, NaNO3, and ZnSO4) upon the recovery of Toxocara ova
      from seeded soil samples with the centrifugal flotation technique was
      investigated. Soil samples of different texture were artificially seeded with
      Toxocara spp. ova and subjected to a centrifugal flotation technique which used
      various flotation solutions. The results showed significant (P < 0.001)
      interactions between the soil types and the flotation solutions. The highest
      percentage of ova recovery was obtained with silty soil (34.9-100.8%) with
      saturated NaCl as the flotation solution (45.3-100.8%). A combination of washing
      of soil samples with 0.1% Tween 80, and flotation using saturated NaCl and a 30
      min coverslip recovery period was used to study the prevalence of contamination
      of soil samples. Forty-six soil samples were collected from up to 24 public
      parks/playgrounds in urban areas of Petaling Jaya and suburban areas of Serdang.
      The prevalence of Toxocara species in the urban and suburban areas was 54.5% and
      45.8% respectively.

PMID- 9639900
TI  - Recovery from arrhythmias in lambs infected with Strongyloides papillosus
      following worm elimination.
AB  - Calves and lambs heavily infected with Strongyloides papillosus develop cardiac
      arrest by ventricular fibrillation which is preceded by continuous sinus
      tachycardia and prolongation of the PQ interval during the patent infection. In
      the present study, cardiac rhythms following anthelmintic treatment were
      investigated in lambs infected with S. papillosus to ascertain whether cardiac
      disorders due to the infection are based on a reversible and curable change.
      Eight lambs were given a lethal dose of S. papillosus. Five of the animals were
      injected with ivermectin when they developed continuous sinus tachycardia and
      prolongation of the PQ interval. The other three animals served as untreated
      controls. In the treated animals, elevated heart rates and PQ intervals began to
      decrease between 10 and 21 h, then continuous sinus tachycardia and prolongation
      of PQ interval disappeared within 39 h of treatment. No arrhythmias were detected
      after the disappearance of sinus tachycardia. Faecal egg counts became negative
      within 61 h of treatment. Only a few worms were collected from the small
      intestine at necropsy. The control animals developed ventricular fibrillation by
      349 h after infection, having high faecal egg counts and intestinal worm burdens.
      These results indicate that cardiac disorders generated by S. papillosus
      infection are reversible and curable following worm elimination.

PMID- 9639901
TI  - Epidemiology of trichinellosis in lynx in Finland.
AB  - Three hundred and twenty seven European lynx (Lynx lynx) were examined for
      Trichinella sp. larvae using the muscle digestion method. The animals were of
      both sexes, various ages, and collected between 1989 and 1994 in different
      locations in Finland. Forty percent of them (132) were found to be infected.
      Infection was overdispersed, so that the majority of infected lynx only harboured
      small amounts of larvae, while a minority had higher densities of infection, but
      never significantly exceeding 40 larvae per gram of muscle (lpg). The median
      density of infection was 1.04 lpg. To find factor statistically associated with
      the risk of infection, multivariate logistic regression analysis was performed.
      Male sex, increasing age, and the density of raccoon dog population in the area
      were all significantly associated with infection. However, the association with
      age was not linear and prevalence did not increase after middle age. The mean
      density of infection decreased slightly with age. The association with the
      density of the raccoon dog population leads to a tentative hypothesis that the
      raccoon dog might be an important reservoir of sylvatic trichinellosis in
      Finland.

PMID- 9639902
TI  - Predictability of morphological gradients in the tapeworm, Hymenolepis diminuta.
AB  - The strobila of an adult tapeworm represents a continual gradient of
      developmental stages from immature to gravid proglottids. The purpose of this
      study was to determine if organogenesis (as measured by the developmental
      gradient) in tapeworms within a single host and among different hosts occurred at
      the same rates. Rats were infected with Hymenolepis diminuta and the tapeworms
      were recovered 20 days post-infection. The total number of proglottids in each
      worm was determined, and five 'benchmarks' of organogenesis were quantified. The
      data demonstrated that organogenesis in worms from a single host occurred at a
      relatively constant rate, but that rates in tapeworms from different hosts were
      different.

PMID- 9639903
TI  - Experimental infection of larval Echinococcus multilocularis in the rodent brain
      as a model for cerebral alveolar echinococcosis.
AB  - Experimental infection of larval Echinococcus multilocularis in the rodent brain
      was attempted to establish a murine model for cerebral alveolar echinococcosis.
      Balb/c mice and jirds were injected intracranially with 10% of a homogenated
      hydatid cyst mass. Small cystic larvae were observed macroscopically in the
      cranial cavity 1, 2 and 5 months post-infection in both mice and jirds. Some
      larval cysts from both rodents contained mature or immature protoscoleces. In
      mice, the laminated layer was found in the lateral ventricle 2 months post
      infection but without protoscoleces. At five months post-infection, larger larval
      cysts were found in the cranial cavity of a mouse, which also demonstrated
      partial palsy of the legs. A laminated layer with mature protoscoleces was
      observed in the third ventricle and the mouse also harboured, in the left lung, a
      larval cyst containing protoscoleces surrounded by lymphocytes. Jirds were also
      found to be infected with metacestodes in the cranial cavity, but neither unusual
      behaviour nor establishment of cysts inside the brain was observed in jirds
      during the course of infection.

PMID- 9639905
TI  - Different levels of Schistosoma mansoni infection induce changes in drug
      metabolizing enzymes.
AB  - Most carcinogens and xenobiotics are metabolized primarily by the mixed function
      oxidase system which includes cytochrome P450, cytochrome b5, NADPH-cytochrome c
      reductase and aryl hydrocarbon [benzo(a)pyrene] hydroxylase. The present study
      investigates the influence of infection with different levels of Schistosoma
      mansoni cercariae on the hepatic levels of reduced glutathione, glutathione S
      transferase and glutathione reductase in addition to the enzymes of mixed
      function oxidase. Cercariae infection levels of 60, 120, 180, 300 and 600 per
      mouse increased: (i) the hepatic content of cytochrome P450 by 27%, 38%, 72%,
      57%, 48% respectively; (ii) the aryl hydrocarbon hydroxylase activity by 44%,
      64%, 76%, 90%, 51% respectively; and (iii) the hepatic level of reduced
      glutathione by 67%, 83%, 103%, 60%, 38% respectively. The cytochrome b5 content
      did not change at the lowest level of infection but increased at the other four
      levels by 45%, 76%, 49% and 38% respectively. The activity of glutathione S
      transferase increased at the first three levels by 42%, 40%, 27% respectively and
      decreased at the last two levels by 28% and 52% respectively. On the other hand,
      the activity of glutathione reductase did not change at any level, whereas, NADPH
      cytochrome c reductase activity decreased at the last two levels by 44% and 54%.
      The alterations in the activities of phase I & II of drug-metabolizing enzymes as
      a result of infection with different levels of S. mansoni may thus change the
      liver's capacity to detoxify many endogenous compounds and may also potentiate
      the deleterious effects of aromatic hydrocarbons, e.g. benzo(a)pyrene, upon the
      liver and probably other organs. Such alterations may also change the therapeutic
      actions of drugs that are primarily metabolized by the P450 system, when
      administered to patients with schistosomiasis.

PMID- 9639906
TI  - Larval trematode infections in freshwater gastropods from the Albufera Natural
      Park in Spain.
AB  - Malacological samplings were made from January 1994 to December 1996 in the
      Albufera Natural Park (Valencia, Spain) to trace the dynamics of molluscan
      populations and the prevalence and intensity of infection by larval trematodes. A
      total of 10,533 freshwater gastropods belonging to seven species (Lymnaea
      auricularia, L. truncatula, L. palustris, L. peregra, Bithynia tentaculata, Physa
      acuta and Gyraulus chinensis) was examined, and 110 (1.04%) were found to harbour
      some of the nine distinguishable types of cercariae, namely four echinostome
      cercariae (Hypoderaeum conoideum, Echinoparyphium recurvatum, Euparyphium
      albuferensis, and Echinostoma sp.), four furcocercous cercariae, and one
      xiphidiocercous cercaria. This study shows that the composition of the snail and
      trematode communities may be determined by the particular environmental
      conditions present and the human intervention in the area.

PMID- 9639907
TI  - Histochemical glycogen and neutral lipid in Echinostoma trivolvis cercariae and
      effects of exogenous glucose on cercarial longevity.
AB  - Histochemical glycogen and neutral lipid studies were conducted on Echinostoma
      trivolvis cercariae maintained in artificial spring water (ASW) at 24-25 degrees
      C for up to 24 h after emergence from host snails. Treatment of whole cercariae
      by the periodic acid Schiff (PAS) reagent with or without 1% malt diastase showed
      that cercariae depleted glycogen mainly from the tail by 6 to 24 h postemergence.
      The posterior tip of the tail remained PAS positive and diastase fast suggesting
      the presence of mucopolysaccharides there. Fresh cercariae or those stained up to
      24 h postemergence with Oil Red O showed the presence of neutral lipid droplets
      in the excretory system. There was no discernible difference in the size,
      abundance, or distribution of these droplets in fresh or aged cercariae.
      Cercariae maintained in ASW plus 1% glucose for 12 or 23 h showed no evidence of
      resynthesizing glycogen. Nevertheless, cercariae survived longer in 1% glucose
      than in either 0.0, 0.1 or 0.5% glucose; but only at 23 h were any differences
      statistically greater (one way ANOVA, P < 0.05).

PMID- 9639908
TI  - Intestinal parasites of the grey fox (Pseudalopex culpaeus) in the central
      Peruvian Andes.
AB  - The intestines of 20 grey Peruvian foxes (Pseudalopex culpaeus) were examined for
      the presence of Echinococcus granulosus and other intestinal parasites.
      Echinococcus granulosus was not found in foxes but Taenia hydatigena and T.
      multiceps were found in 7 and 4 animals respectively. The grey fox may not be a
      suitable definitive host for E. granulosus. However, it may act as a sylvatic
      reservoir of T. hydatigena and T. multiceps in the central Peruvian Andes.

PMID- 9639909
TI  - Maintenance of Helisoma trivolvis naturally infected with Echinostoma trivolvis
      in spring water at 4 degrees C for 300 days.
AB  - Helisoma trivolvis (Pennsylvania strain) snails naturally infected with
      Echinostoma trivolvis larvae were maintained for 10 months (300 days) at 4
      degrees C in artificial spring water to determine the effects of storage on
      parasite survival. Three of 20 snails were alive at 10 months and when isolated
      in spring water at 22-24 degrees C released active cercariae. The mean number of
      cercariae released in 2 h from each stored snail was significantly less than that
      from freshly collected snails. Infectivity of cercariae from stored hosts to
      experimentally infected, laboratory-raised Helisoma trivolvis (Colorado strain)
      snails was significantly less than that of cercariae from fresh hosts based on
      cyst recoveries in the Colorado strain of H. trivolvis within 24 h p.i. There was
      no significant difference in the redial number or the number of cercariae per
      redia in stored versus fresh snails. In conclusion, some reduction in cercarial
      emergence and decrease in cercarial infectivity to a second intermediate snail
      host occurred following storage of H. trivolvis naturally infected with E.
      trivolvis in ASW at 4 degrees C for 10 months.

PMID- 9639910
TI  - Photosensitizing drugs containing the benzophenone chromophore.
AB  - The nonsteroidal anti-inflammatory agents ketoprofen, tiaprofenic acid, suprofen
      and tolmetin, together with the anti-hyperlipoproteinemic drug fenofibrate and
      the anti-arrhythmic amiodarone can be included in the group of benzophenone
      derived photosensitizing drugs. They contain a diaryl ketone chromophore and
      mediate the development of phototoxic reactions. In some cases, photoallergic
      responses have been reported. These properties have been substantiated in
      clinical reports, as well as by means of in vivo and in vitro assays. Tolmetin is
      phototoxic in vitro, however there are no reports on photosensitization by this
      drug in humans. In general, photochemical and photobiological studies strongly
      suggest that photosensitization involves formal hydrogen abstraction (either in a
      single step or via electron transfer followed by proton transfer) by the
      benzophenone-like chromophore from the excited triplet state. In the case of
      amiodarone, the radicals generated by photodehalogenation from the triplet are
      responsible for the photosensitivity side-effects.

PMID- 9639911
TI  - Photodynamic therapy as a tool for suppressing the haematogenous dissemination of
      tumour cells.
AB  - The chance of most cancer patients surviving their disease is to a high degree
      dependent on the status of the metastatic processes. One general route of cancer
      cell dissemination is passive transport in the blood stream, i.e., haematogenous
      dissemination. In this study we try to find an answer to the following question:
      is it possible to use photodynamic therapy for suppressing the haematogenous
      dissemination of cancer cells? In first in vitro experiments we incubated CX1
      cells (colon carcinoma cells) with two photosensitizers, Photofrin II and
      mesotetra(hydroxyphenyl)chlorin (mTHPC). We added the cells to fresh whole blood
      and irradiated the blood with suitable laser light in a flow-through irradiation
      system. The tumour-cell survival fraction (SF) was determined with plating
      efficiency. Using Photofrin II we observed a minimal tumour-cell survival in
      blood of SF = 3.5% and using mTHPC we measured SF = 0.02%. These results
      encourage further investigations concerning the use of photodynamic therapy for
      suppressing haematogenous dissemination.

PMID- 9639912
TI  - A robust, inexpensive filter for blocking UVC radiation in broad-spectrum 'UVB'
      lamps.
AB  - Accurate studies of the biological effects of UBV radiation require suitable
      laboratory sources. Lamps labeled as UVB sources often emit UVC radiation that
      contributes significantly to the levels of DNA damage. The UVC from an unfiltered
      UVB source produced more pyrimidine dimers in soybean DNA than a lamp filtered by
      a Pyrex dish that removes wavelengths of < 280 nm. Calculations based on action
      spectra and on the emission spectra of unfiltered lamps indicate that UVC
      contributes approximately 13%, 4% and approximately 1% of the total dimers
      induced in unshielded cells or DNA, alfalfa cotyledons, and human skin,
      respectively. Further, relative to a Pyrex dish-filtered lamp, an unfiltered lamp
      would produce approximately 7-, 2.4- or 2.8-fold more dimers in these three
      biological systems. We report here that a Pyrex dish provides an effective,
      stable, robust and inexpensive filter for reducing or excluding the contribution
      of UVC to damage induced by broad-spectrum 'UVB' lamps.

PMID- 9639913
TI  - Raman spectroscopic study of microcosmic and photosensitive damage on the
      liposomes of the mixed phospholipids sensitized by hypocrellin and its
      derivatives.
AB  - Using Raman spectroscopy, we studied and compared the characteristics of
      microcosmic and photosensitive damage of the liposomes of mixed DPPE and DPPC
      sensitized by hypocrellin and its derivatives at the molecular level. After
      photosensitive damage, the structure of the liposomes of mixed phospholipids
      changed considerably. The trans conformation decreased and gauche conformation
      increased. The longitudinal order parameter in chains and the lateral order
      parameter between chains decreased clearly. The results suggested that the
      hydrocarbon chains of DPPE and DPPC were broken after the photodamage sensitized
      by hypocrellin B (HB) and 5-Br-hypocrellin B (5-Br-HB). Photosensitive damage on
      the liposomes sensitized by 5-Br-HB is stronger than that by hypocrellin A (HA)
      and HB, that is, 5-Br-HB > HB > HA. The results elucidated the sites of
      interaction or binding to HA, HB and 5-Br-HB in the liposomes and these changed
      with the use of drugs.

PMID- 9639914
TI  - Spatial measurement of oxygen levels during photodynamic therapy using time
      resolved optical spectroscopy.
AB  - Tissue oxygenation is one of the key dosimetric factors involved in the
      application of photodynamic therapy (PDT). However, quantitative studies of
      oxygenation levels at and surrounding the treatment site have been lacking both
      before, during and after treatment. With the recent development of sensitive, non
      invasive, optical spectroscopic techniques based on oxygen-dependent
      phosphorescence quenching of probe compounds, oxygenation levels can now be
      measured quantitatively at selected sites with spatial resolution on the
      millimeter scale. We present results using the phosphorescent compound, palladium
      meso-tetra(carboxyphenyl)porphine, for measurement of in vivo microvascular
      oxygen tensions in rat liver during PDT. Time-resolved phosphorescence detection
      was carried out using fibre-optic sensoring, and oxygen tensions were determined
      from the phosphorescence lifetimes using Stern-Volmer analysis. During PDT
      treatment using 5-aminolaevulinic (ALA) acid-induced protoporphyrin IX (PPIX)
      with a 50 mg/kg ALA dose, oxygen levels near the irradiation fibre placed on the
      surface of the liver showed a significant decrease by a factor of ten from 20 to
      2 torr after an energy dose of 60 J using 100 mW at 635 nm. Areas farther from
      the treatment site which were exposed to lower light doses exhibited lower
      reductions in oxygen levels. This spectroscopic technique is a highly sensitive
      means of investigating tissue oxygenation during and after treatment, and should
      help not only to advance the understanding of hypoxia and microvascular damage in
      the PDT mechanism but also contribute to improving the dosimetry of PDT.

PMID- 9639915
TI  - Synergistic effect of UVB radiation and age on HMPS enzymes in rat lens
      homogenate.
AB  - The behaviour of rat lenticular enzymes, glucose-6-phosphate dehydrogenase (G6PD,
      EC: 1.1.1.49) and 6-phosphogluconate dehydrogenase (6PGD, EC: 1.1.1.44) as a
      function of age and UVB irradiation (in vitro) was investigated by irradiating
      the lens homogenate from 3- and 12-month-old rats at 300 nm (100 microW cm-2). In
      the 3-month-old group the specific activities of G6PD and 6PGD were reduced by
      26% and 42%, respectively, after 24 h of irradiation, whereas in the 12-month-old
      group the decrease was 38% and 49% respectively, which suggests that the
      susceptibility of HMPS enzymes to UVB damage is higher in older lenses. The
      decrease in specific activity was associated with a change in apparent K(m) and
      Vmax (marginal in 3 months and significant in 12 months) of these enzymes due to
      UVB irradiation. UVB irradiation also decreased the levels of NADPH and
      NADPH/NADP ratio. These changes, altered activities of G6PD and 6PGD and altered
      levels of NADPH, may in turn have a bearing on lens transparency.

PMID- 9639917
TI  - Investigating biological response in the UVB as a function of ozone variation
      using perturbation theory.
AB  - In order to determine a biological response to ultraviolet radiation,
      calculations of biologically weighted dose rates are required, which in turn
      involve the integral over wavelength of an action spectrum multiplied by
      appropriate surface flux data. To determine a biologically weighted dose rate
      accurately, a reasonable wavelength resolution is required, involving a full
      radiative transfer solution to be performed for each wavelength in order to
      obtain the surface flux information. If biologically weighted dose rates are
      needed as a function of ozone variation, then the number of radiative transfer
      solutions quickly makes a large number of ozone variations cumbersome. This paper
      shows that the perturbation theory developed for atmospheric radiative transfer
      by Box and co-workers can predict surface fluxes and hence biologically weighted
      dose rates for a large range of ozone variations very efficiently. The method is
      then extended to calculate radiation amplification factors. Results for
      biologically weighted dose rates are presented for a large range of solar zenith
      angles and ozone loadings using perturbation theory and a full radiative transfer
      code and show that the perturbation predictions never deviate very far from the
      radiative transfer solutions.

PMID- 9639916
TI  - Hemodynamic effects of 5-aminolevulinic acid in humans.
AB  - Endogenous protoporphyrin IX (PpIX), which results from the oral administration
      of 5-aminolevulinic acid (ALA), is being investigated for its efficacy as a
      photosensitizing agent for photodynamic therapy (PDT). Clinical use of ALA has
      been associated with only mild gastrointestinal side effects. The hemodynamic
      effects of orally administered ALA in doses used for PDT are unknown. Six
      patients with a significant history of cardiac disease underwent Swan-Ganz
      catheterization prior to ALA administration and abdominal operation for PDT.
      Hemodynamic data collection began at least 1 h prior to ALA, and continued for at
      least 4 h subsequently, during which time no other medications were administered.
      When compared to measurements made prior to ALA administration, all patients
      displayed a significant decrease in systolic and diastolic blood pressures,
      pulmonary artery systolic and diastolic pressures as well as pulmonary vascular
      resistance. Five of the six patients also developed a decrease in systemic
      vascular resistance. No significant changes in pulmonary capillary wedge
      pressure, cardiac output or cardiac index was observed, but the mean pulse rate
      rose significantly. These findings cannot be explained on the basis of other
      cardiovascular depressants or to poor central volume status. Although no adverse
      sequela were appreciated as a result of the observed hemodynamic changes, this
      potential should be recognized in patients undergoing PDT using ALA.

PMID- 9639918
TI  - Insertion mutagenesis of XpsD, an outer-membrane protein involved in
      extracellular protein secretion in Xanthomonas campestris pv. campestris.
AB  - XpsD is an outer-membrane protein required for extracellular protein secretion in
      Xanthomonas campestris pv. campestris. Cross-linking and gelfiltration
      chromatography analyses have suggested that it forms a multimer. To determine its
      structure-function relationship, linker-insertion mutants were constructed in an
      xpsD gene carried on a plasmid. To assay for secretion function, each mutant gene
      was introduced into an xpsD::Tn5 mutant strain (XC1708) and assayed for alpha
      amylase secretion on starch plates. To test whether the mutant genes exerted a
      dominant-negative effect, each was introduced into the parental strain XC1701 and
      examined for secretion interference. Nine functional, one semi-functional and
      eleven non-functional mutants were obtained. All the non-functional mutants,
      except two for which the mutant proteins were undetectable on immunoblots, showed
      interference of normal secretion. The insertion sites in the different mutant
      proteins are randomly distributed throughout the entire sequence of the XpsD
      protein. All the permissive insertion sites are located where beta-turn or coiled
      secondary structure is predicted. Over half of the non-permissive sites are
      located within predicted helical or beta-sheet regions. By pretreating total
      membranes of XC1701 in SDS at 50 degrees C, an immunoreactive band with high
      molecular mass (HMM) could be detected that remained in the stacking gel during
      SDS-PAGE. The semi-functional and all functional mutant proteins formed HMM
      complexes that were as SDS-resistant as those of the wild-type, whereas all
      except three of the non-functional mutant proteins formed HMM structures that
      were less resistant to SDS than the wild-type. By analysing the appearance of SDS
      resistant HMM complexes, we were able to detect conformational alterations in
      XpsD that are too subtle to be detected by other assays.

PMID- 9639919
TI  - Evidence for a role for the gumB and gumC gene products in the formation of
      xanthan from its pentasaccharide repeating unit by Xanthomonas campestris.
AB  - The biosynthesis of the extracellular polysaccharide xanthan in Xanthomonas
      campestris pv. campestris is directed by a cluster of 12 genes, gumB-gumM.
      Several xanthan-deficient mutants of the wild-type strain 8004 have previously
      been described which carry Tn5 insertions in this region of the chromosome. Here
      it is shown that the transposon insertion in one of these mutants, strain 8397,
      is located 15 bp upstream of the translational start site of the gumB gene. EDTA
      treated cells of strain 8397 were able to synthesize the lipid-linked
      pentasaccharide repeating unit of xanthan from the three nucleotide sugar donors
      (UDP-glucose, GDP-mannose and UDP-glucuronic acid) but were unable to polymerize
      the pentasaccharide into mature xanthan. A subclone of the gum gene cluster
      carrying gumB and gumC restored xanthan production to strain 8397 to levels
      approximately 28% of the wild-type. In contrast, subclones carrying gumB or gumC
      alone were not effective. These results are discussed with reference to previous
      speculations, based on computer analysis, that gumB and gumC are both involved in
      the translocation of xanthan across the bacterial membranes.

PMID- 9639920
TI  - Cryptic carbapenem antibiotic production genes are widespread in Erwinia
      carotovora: facile trans activation by the carR transcriptional regulator.
AB  - Few strains of Erwinia carotovora subsp. carotovora (Ecc) make carbapenem
      antibiotics. Strain GS101 makes the basic carbapenem molecule, 1-carbapen-2-em-3
      carboxylic acid (Car). The production of this antibiotic has been shown to be
      cell density dependent, requiring the accumulation of the small diffusible
      molecule N-(3-oxohexanoyl)-L-homoserine lactone (OHHL) in the growth medium. When
      the concentration of this inducer rises above a threshold level, OHHL is proposed
      to interact with the transcriptional activator of the carbapenem cluster (CarR)
      and induce carbapenem biosynthesis. The introduction of the GS101 carR gene into
      an Ecc strain (SCRI 193) which is naturally carbapenem-negative resulted in the
      production of Car. This suggested that strain SCRI 193 contained functional
      cryptic carbapenem biosynthetic genes, but lacked a functional carR homologue.
      The distribution of trans-activatable antibiotic genes was assayed in Erwinia
      strains from a culture collection and was found to be common in a large
      proportion of Ecc strains. Significantly, amongst the Ecc strains identified, a
      larger proportion contained trans-activatable cryptic genes than produced
      antibiotics constitutively. Southern hybridization of the chromosomal DNA of
      cryptic Ecc strains confirmed the presence of both the car biosynthetic cluster
      and the regulatory genes. Identification of homologues of the transcriptional
      activator carR suggests that the cause of the silencing of the carbapenem
      biosynthetic cluster in these strains is not the deletion of carR. In an attempt
      to identify the cause of the silencing in the Ecc strain SCRI 193 the carR
      homologue from this strain was cloned and sequenced. The SCRI 193 CarR homologue
      was 94% identical to the GS101 CarR and contained 14 amino acid substitutions.
      Both homologues could be expressed from their native promoters and ribosome
      binding sites using an in vitro prokaryotic transcription and translation assay,
      and when the SCRI 193 carR homologue was cloned in multicopy plasmids and
      reintroduced into SCRI 193, antibiotic production was observed. This suggested
      that the mutation causing the silencing of the biosynthetic cluster in SCRI 193
      was leaky and the cryptic Car phenotype could be suppressed by multiple copies of
      the apparently mutant transcriptional activator.

PMID- 9639921
TI  - Yersinia pseudotuberculosis and Yersinia pestis are more resistant to
      bactericidal cationic peptides than Yersinia enterocolitica.
AB  - The action of bactericidal polycationic peptides was compared in Yersinia spp. by
      testing peptide binding to live cells and changes in outer membrane (OM)
      morphology and permeability. Moreover, polycation interaction with LPS was
      studied by measuring the dependence of dansylcadaverine displacement and zeta
      potential on polycation concentration. When growth at 37 degrees C, Yersinia
      pestis and Yersinia pseudotuberculosis bound less polymyxin B (PMB) than
      pathogenic or non-pathogenic Yersinia enterocolitica, regardless of virulence
      plasmid expression. Y. pseudotuberculosis OMs were unharmed by PMB concentrations
      causing extensive OM blebbing in Y. enterocolitica. The permeability to lysozyme
      caused by PMB was greater in Y. enterocolitica than in Y. pseudotuberculosis or
      Y. pestis and differences increased at 37 degrees C. Similar observations were
      made with other polycations using a polymyxin/novobiocin permeability assay. With
      LPS of cells grown at 26 degrees C, polycation binding was highest for Y.
      pseudotuberculosis and lowest for Y. pestis, with Y. enterocolitica yielding
      intermediate results which were lower for pathogenic than for non-pathogenic
      strains. With LPS of cells grown at 37 degrees C, polycation binding remained
      unchanged for Y. pestis and pathogenic Y. enterocolitica, increased for non
      pathogenic Y. enterocolitica and decreased for Y. pseudotuberculosis to Y. pestis
      levels. Polycation binding related in part to differences in charge density (zeta
      potential) of LPS aggregates, suggesting similar effects at bacterial surfaces.
      It is suggested that species and temperature differences in polycation resistance
      relate to infection route, invasiveness and intracellular multiplication of
      Yersinia spp.

PMID- 9639922
TI  - Yersinia pseudotuberculosis and Yersinia pestis show increased outer membrane
      permeability to hydrophobic agents which correlates with lipopolysaccharide acyl
      chain fluidity.
AB  - The hydrophobic probe N-phenyl-1-naphthylamine accumulated less in non-pathogenic
      Yersinia spp. and non-pathogenic and pathogenic Yersinia enterocolitica than in
      Yersinia pseudotuberculosis or Yersinia pestis. This was largely due to
      differences in the activity of efflux systems, but also to differences in outer
      membrane permeability because uptake of the probe in KCN/arsenate-poisoned cells
      was slower in the former group than in Y. pseudotuberculosis and Y. pestis. The
      probe accumulation rate was higher in Y. pseudotuberculosis and Y. pestis grown
      at 37 degrees C than at 26 degrees C and was always highest in Y. pestis. These
      yersiniae had LPSs with shorter polysaccharides than Y. enterocolitica,
      particularly when grown at 37 degrees C. Gel<-->liquid-crystalline phase
      transitions (Tc 28-31 degrees C) were observed in LPS aggregates of Y.
      enterocolitica grown at 26 and 37 degrees C, with no differences between non
      pathogenic and pathogenic strains. Y. pseudotuberculosis and Y. pestis LPSs
      showed no phase transitions and, although the fluidity of LPSs of Y.
      pseudotuberculosis and Y. enterocolitica grown at 26 degrees C were close below
      the Tc of the latter, they were always in a more fluid state than Y.
      enterocolitica LPS. Comparison with previous studies of Salmonella choleraesuis
      subsp. choleraesuis serotype minnesota rough LPS showed that the increased
      fluidity and absence of transition of Y. pseudotuberculosis and Y. pestis LPSs
      cannot be explained by their shorter polysaccharides and suggested differences at
      the lipid A/core level. It is proposed that differences in LPS-LPS interactions
      and efflux activity explain the above observations and reflect the adaptation of
      Yersinia spp. to different habitats.

PMID- 9639923
TI  - Lipopolysaccharide expression within the genus Bordetella: influence of
      temperature and phase variation.
AB  - LPSs play an important role in bacterial pathogenesis. In this study, the LPS
      expression of the seven known Bordetella species and its dependency on growth
      temperature was analysed by oxidative silver staining of proteinase-K-treated
      whole bacteria separated by Tricine-SDS-PAGE. The bordetellae were found to have
      extensively variable LPS in a species-specific way. In addition, the human and
      ovine Bordetella parapertussis strains exhibited host-specific LPS expression.
      LPSs from human B. parapertussis strains grown at 37 and 25 degrees C were
      distinct. Growth temperature also affected LPS production by several Bordetella
      bronchiseptica strains. In some of these cases, BvgAS, the global regulator of
      virulence factors, was involved in this regulation of LPS biosynthesis. In
      contrast, no evidence was found for the involvement of the Bordetella pertussis
      BvgAS system in regulation of LPS synthesis. The obligate human pathogens B.
      pertussis and Bordetella holmesii are closely related but were shown to produce
      immunologically distinct LPSs. These species are isolated from the upper
      respiratory tract and blood, respectively. This raises several interesting
      questions concerning the potential role of LPS as a virulence factor in the
      infection processes.

PMID- 9639924
TI  - Characterization of the glnB gene product of Nostoc punctiforme strain ATCC
      29133: glnB or the PII protein may be essential.
AB  - Bacterial PII proteins, encoded by glnB genes, are central signalling molecules
      in nitrogen regulatory pathways and are modulated by post-translational
      modification in response to the cellular nitrogen status. The glnB gene was
      cloned from the filamentous heterocyst-forming cyanobacterium Nostoc punctiforme
      strain ATCC 29133 (PCC 73102) by heterologous hybridization to a Synechococcus
      sp. strain PCC 7942 gene fragment. Expression of the cloned gene was verified by
      hybridization to N. punctiforme total RNA and a single cross-reactive polypeptide
      was observed in immunoblots of N. punctiforme extracts probed with anti
      Synechococcus 7942 PII antiserum. Modification of the purified N. punctiforme PII
      protein by a Synechococcus 7942 PII kinase was observed, but modified forms of
      PII were not detected in extracts of N. punctiforme from a variety of incubation
      conditions. The N. punctiforme glnB gene could not be disrupted by targeted gene
      replacement unless a second copy of glnB was provided in trans, suggesting that
      the gene or gene product is essential for growth under the conditions tested.

PMID- 9639925
TI  - Multiple oligomeric forms of glucose-6-phosphate dehydrogenase in cyanobacteria
      and the role of OpcA in the assembly process.
AB  - Multiple molecular forms of glucose-6-phosphate dehydrogenase (G6PDH) were
      detected by activity staining in non-denaturing polyacrylamide gels of cell-free
      extracts from a range of cyanobacteria including Anabaena sp. PCC 7120,
      Synechococcus sp. PCC 7942, Plectonema boryanum PCC 73110, Synechocystis sp. PCC
      6803, Nostoc sp. MAC PCC 8009 and the marine strain Synechococcus sp. WH7803. In
      most of the species tested, the profile of G6PDH activities was modulated by the
      growth of the cells in the presence of exogenous 10 mM glucose. Using an
      antiserum raised against a fragment of G6PDH from Anabaena sp. PCC 7120, it was
      shown that the different molecular forms of G6PDH all contained an antigenically
      related subunit, suggesting that the different forms arose from different
      quaternary structures involving the same monomer. An insertion mutant of
      Synechococcus sp. PCC 7942 was constructed in which the opcA gene, adjacent to
      zwf (encoding G6PDH), was disrupted. Although no reduction in the amount of G6PDH
      monomers (Zwf) was observed in the opcA mutant, activity staining of native gels
      indicated that most of this protein is not assembled into one of the active
      oligomeric forms. The oligomerization of G6PDH in extracts of the opcA mutant was
      stimulated in vitro by a factor present in crude extracts of the wild-type,
      suggesting that the product of the opcA gene is involved in the oligomerization
      and activation of G6PDH.

PMID- 9639926
TI  - Pleiotropic effects of potassium deficiency in a heterocystous, nitrogen-fixing
      cyanobacterium, Anabaena torulosa.
AB  - Omission of potassium from the growth medium caused multiple metabolic
      impairments and resulted in cessation of growth of the filamentous,
      heterocystous, nitrogen-fixing cyanobacterium Anabaena torulosa, during both
      diazotrophic and nitrogen-supplemented growth. Prominent defects observed during
      potassium deprivation were: (i) the loss of photosynthetic pigments, (ii)
      impairment of photosynthetic functions, (iii) reduced synthesis of dinitrogenase
      reductase (Fe-protein), (iv) inhibition of nitrogenase activity, and (v) specific
      qualitative modifications of protein synthesis leading to the repression of
      twelve polypeptides and synthesis and accumulation of nine novel polypeptides.
      The observed metabolic defects were reversible, and growth arrested under
      prolonged potassium deficiency was fully restored upon re-addition of potassium.
      Such pleiotropic effects of potassium deficiency demonstrate that apart from its
      well-known requirement for pH and turgor homeostasis, K+ plays other vital
      specific roles in cyanobacterial growth and metabolism.

PMID- 9639927
TI  - Phytase activity of anaerobic ruminal bacteria.
AB  - Phytase catalyses the release of phosphate from phytate (myo-inositol
      hexakisphosphate), the predominant form of phosphorus in cereal grains, oilseeds
      and legumes. The presence of phytase activity was investigated in 334 strains of
      22 species of obligately anaerobic ruminal bacteria. Measurable activities were
      demonstrated in strains of Selenomonas ruminantium, Megasphaera elsdenii,
      Prevotella ruminicola, Mitsuokella multiacidus and Treponema spp. Strains
      isolated from fermentations with cereal grains proved to have high activity, and
      activity was particularly prevalent in S. ruminantium, with over 96% of the
      tested strains being positive. The measured phytase activity was found
      exclusively associated with the bacterial cells and was produced in the presence
      of approximately 14 mM phosphate. The most highly active strains were all S.
      ruminantium, with the exception of the one Mitsuokella multiacidus strain
      examined. Phytase activity varied greatly among positive strains but activities
      as high as 703 nmol phosphate released (ml culture)-1 were measured for a S.
      ruminantium strain and 387 nmol phosphate released (ml culture)-1 for the
      Mitsuokella multiacidus strain.

PMID- 9639928
TI  - Inducible chitinolytic system of Aspergillus fumigatus.
AB  - Incubation of Aspergillus fumigatus NCPF 2140 in growth medium containing 1%
      chitin as sole carbon source led to induction of specific extracellular
      chitinolytic activity of 1.5 mumol GlcNAc released min-1 (mg protein)-1. The
      effect was repressed by the inclusion of GlcNAc in the medium, indicating
      regulation by a negative feedback mechanism. Extracellular chitinase activity was
      inhibited by allosamidin (IC50 0.12 microM). Multiple chitinolytic enzymes were
      detected on zymograms of extracellular preparations; levels of individual enzymes
      induced were dependent upon whether cells were incubated with purified colloidal
      chitin or a crude preparation of crystalline chitin. A major, inducible, 45 kDa
      chitinase was purified using ammonium sulphate precipitation, chitin affinity
      chromatography and a novel procedure involving the electroelution of the enzyme
      from a substrate gel containing glycol chitin. The enzyme is a glycoprotein with
      endochitinase activity.

PMID- 9639929
TI  - Characterization of a second cell-associated Arg-specific cysteine proteinase of
      Porphyromonas gingivalis and identification of an adhesin-binding motif involved
      in association of the prtR and prtK proteinases and adhesins into large
      complexes.
AB  - Porphyromonas gingivalis has been associated with the development of adult
      periodontitis and cysteine proteinases with Arg- and Lys-specific activity have
      been implicated as major virulence factors. In a cell sonicate of P. gingivalis
      W50, a complex of non-covalently associated proteins has been previously
      characterized. This complex is composed of a 45 kDa Arg-specific, calcium
      stabilized cysteine proteinase (PrtR45), a 48 kDa Lys-specific cysteine
      proteinase (PrtK48) and seven sequence-related adhesins designated PrtR44,
      PrtR15, PrtR17, PrtR27, PrtK39, PrtK15 and PrtK44, with all proteins being
      encoded by the two genes prtR and prtK. It has been proposed that these non
      covalently associated complexes form extracellularly after autolytic processing
      of the PrtR and PrtK polyproteins, with the adhesins binding to the proteinases
      (PrtR45 and PrtK48) and autoaggregating. Another form of the cell-associated, Arg
      specific, calcium-stabilized cysteine proteinase is described here. Designated
      PrtRII50, it is a discrete 50 kDa protein with no adhesin-association and has
      enzymic characteristics and an inhibitor/activator profile almost identical to
      PrtR45. The PrtRII50 proteinase is encoded as a preproprotein by a second gene,
      prtRII, with high sequence similarity to PrtR except that it lacks the C-terminal
      adhesin domains. A comparison of the deduced amino acid sequence of PrtRII50 with
      that of the adhesin-associated proteinases PrtR45 and PrtK48 revealed that
      PrtRII50 does not contain a C-terminal motif that is conserved in PrtR45 and
      PrtK48. Related motifs are also found in the adhesin domains of PrtR and PrtK. It
      is proposed that this conserved motif is an adhesin-binding motif (ABM) involved
      in association of the PrtR and PrtK proteinases and adhesins into large
      complexes, as the PrtR-PrtK proteinase-adhesin complex inactivated by N-alpha-p
      tosyl-L-lysine chloromethyl ketone (TLCK) was shown to bind specifically to a
      synthetic peptide corresponding to the conserved motif in a competitive binding
      assay.

PMID- 9639930
TI  - The yvsA-yvqA (293 degrees-289 degrees) region of the Bacillus subtilis
      chromosome containing genes involved in metal ion uptake and a putative sigma
      factor.
AB  - The region between yvsA (293 degrees) and yvqA (289 degrees) of the Bacillus
      subtilis chromosome has been sequenced within the framework of the B. subtilis
      168 international sequencing programme. A primary analysis of the 42 ORFs
      identified in this 43 kb region is presented. The region included a high
      proportion of genes that did not show homology with genes in other bacteria. The
      identified ORFs showed homology to proteins involved in the transport of metal
      ions, two-component signal transducers, ATP-binding-cassette-type transporters
      and a sigma factor.

PMID- 9639931
TI  - Psychroflexus torquis gen. nov., sp. nov., a psychrophilic species from Antarctic
      sea ice, and reclassification of Flavobacterium gondwanense (Dobson et al. 1993)
      as Psychroflexus gondwanense gen. nov., comb. nov.
AB  - A group of sea-ice-derived psychrophilic bacterial strains possessing the unusual
      ability to synthesize the polyunsaturated fatty acids eicosapentaenoic acid (20:5
      omega 3) and arachidonic acid (20:4 omega 6) belong to the Family
      Flavobacteriaceae (Flexibacter-Bacteroides-Flavobacterium phylum), according to
      16S rRNA sequence analysis. Surprisingly, the isolates were also found to cluster
      closely to the moderately halophilic and psychrotrophic species [Flavobacterium]
      gondwanense (sequence similarity 97.8-98.1%). The whole-cell fatty acid profiles
      of this group and [Flavobacterium] gondwanense were very similar and distinct
      from other related flavobacteria. The sea ice strains and [Flavobacterium]
      gondwanense differed substantially in terms of ecophysiology, possibly
      representing divergent adaptations to sympagic and planktonic marine habitats,
      respectively. Evidence based on phylogeny and fatty acid profiles supports the
      conclusion that the taxa are close relatives distinct from other bacterial
      groups. It is thus proposed that the sea ice strains represent a novel taxon
      designated Psychroflexus torquis gen. nov., sp. nov. (type strain ACAM 623T)
      while [Flavobacterium] gondwanense becomes Psychroflexus gondwanense gen. nov.,
      comb. nov.

PMID- 9639932
TI  - PAGE analysis of the heteroduplexes formed between PCR-amplified 16S rRNA genes:
      estimation of sequence similarity and rDNA complexity.
AB  - Analysis of the 16S rRNA genes retrieved directly from different environments has
      proven to be a powerful tool that has greatly expanded our knowledge of microbial
      diversity and phylogeny. It is shown here that sequence similarity between 80 and
      100% among 16S rDNAs can be estimated by the electrophoretic migration of their
      heteroduplexes. This was measured by hybridization and electrophoresis in
      polyacrylamide gels of the product obtained after PCR amplification of almost the
      entire 16S rRNA gene from different bacterial species. These heteroduplexes were
      also observed after amplification of samples containing DNA from two or more
      bacterial species and a procedure was applied to identify reliably heteroduplexes
      among the amplification products. The electrophoretic migration of the
      heteroduplexes observed after PCR was used to detect the presence of 16S rDNAs
      with different sequences in DNA extracted from both a mixture of two bacterial
      species and samples containing a natural bacterial community.

PMID- 9639933
TI  - Identification of Mycobacterium tuberculosis signal sequences that direct the
      export of a leaderless beta-lactamase gene product in Escherichia coli.
AB  - Proteins secreted by Mycobacterium tuberculosis may play a key role in virulence
      and may also constitute antigens that elicit the host immune response. However,
      the M. tuberculosis protein export machinery has not been characterized. A
      library of M. tuberculosis H37Rv genomic DNA fragments ligated into a signal
      sequence selection vector that contained a leaderless beta-lactamase gene and an
      upstream Tac promoter was constructed. Transformation of Escherichia coli with
      the M. tuberculosis DNA library and selection on plates containing 50-100
      micrograms ampicillin ml-1 resulted in the identification of 15 Ampr clones out
      of a total of 14,000 transformants. Twelve of the beta-lactamase gene fusions
      conferred high levels of Ampr (up to 1 mg ampicillin ml-1); insert sizes ranged
      from 350 to 3000 bp. Of ten inserts that were completely sequenced, two were
      identified as fragments of the genes for M. tuberculosis antigens 85A and 85C,
      which are the major secreted proteins of this pathogen. Seven of the remaining
      inserts were > or = 97% identical to hypothetical ORFs in the M. tuberculosis
      genome, one of which encoded a protein with 35% identity to a low-affinity
      penicillin-binding protein (PBP) from Streptomyces clavuligerus. Four of the
      seven hypothetical ORFs encoded putative exported proteins with one or more
      membrane interaction elements, including lipoprotein attachment sites and type I
      and II transmembrane (TM) segments. All of the inserts encoded typical signal
      sequences, with the exception of a possible type II membrane protein. It is
      concluded that expression of beta-lactamase gene fusions in E. coli provides a
      useful system for the identification and analysis of M. tuberculosis signal
      sequence-encoding genes.

PMID- 9639934
TI  - Genes for D-arabinitol and ribitol catabolism from Klebsiella pneumoniae.
AB  - The enzymes for catabolism of the pentitols D-arabinitol (Dal) and ribitol (Rbt)
      and the corresponding genes from Klebsiella pneumoniae (dal and rbt) and
      Escherichia coli (atl and rtl) have been used intensively in experimental
      evolutionary studies. Four dal and four rbt genes from the chromosome of K.
      pneumoniae 1033-5P14 were cloned and sequenced. These genes are clustered in two
      adjacent but divergently transcribed operons and separated by two convergently
      transcribed repressor genes, dalR and rbtR. Each operon encodes an NAD-dependent
      pentose dehydrogenase (dalD and rbtD), and ATP-dependent pentulose kinase (dalK
      and rbtK) and a pentose-specific ion symporter (dalT and rbtT). Although the
      biochemical reactions which they catalyse are highly similar, the enzymes showed
      interesting deviations. Thus, DalR (313 aa) and RbtR (270 aa) belong to different
      repressor families, and DalD (455 aa) and RbtD (248 aa), which are active as a
      monomer or as tetramers, respectively, belong to different dehydrogenase
      families. Of the two kinases (19.3% identity), DalK (487 aa) belongs to the
      subfamily of short D-xylulokinases and RbtK (D-ribulokinase; 535 aa) to the
      subfamily of long kinases. The repressor, dehydrogenase and kinase genes did not
      show extensive similarity beyond local motifs. This contrasts with the ion
      symporters (86.6% identity) and their genes (82.7% identity). Due to their
      unusually high similarity, parts of dalT and rbtT have previously been claimed
      erroneously to correspond to 'inverted repeats' and possible remnants of a
      'metabolic transposon' comprising the dal and rbt genes. Other characteristic
      structures, e.g. a secondary att lambda site and chi-like sites, as well as the
      conservation of this gene group in E. coli C are also discussed.

PMID- 9639935
TI  - Molecular analysis of the DNA gyrB gene from Myxococcus xanthus.
AB  - DNA gyrase, an essential type II topoisomerase, mediates negative supercoiling of
      the bacterial chromosome, thereby affecting the processes of DNA replication,
      transcription, recombination and repair. The gyrB gene from the Gram-negative
      soil bacterium Myxococcus xanthus was sequenced. The sequence predicts a protein
      of 815 amino acid residues displaying significant homology to all known GyrB
      proteins. A 6-His-GyrB fusion protein was overexpressed in Escherichia coli and
      purified to near homogeneity using affinity chromatography on Ni-nitrilotriacetic
      acid-agarose and novobiocin-Sepharose columns. The fusion protein bound
      novobiocin and cross-reacted with anti-E. coli GyrB antibodies, indicating
      structural and functional similarities to the E. coli DNA GyrB. The gene was
      mapped to the region of the origin of replication (oriC) of M. xanthus.

PMID- 9639936
TI  - The NADH-dependent glutamate dehydrogenase enzyme of Bacteroides fragilis Bf1 is
      induced by peptides in the growth medium.
AB  - Bacteroides fragilis Bf1 possesses two enzymes having glutamate dehydrogenase
      (GDH) activity. One is dual cofactor NAD(P)H-dependent, while the other has NADH
      specific activity. The gene encoding the NADH-GDH (gdhB) was cloned by
      complementation of the glutamate auxotrophic mutant Escherichia coli MX3004 and
      the recombinant protein was characterized with respect to the GDH activities
      present in the parental organism grown under different nitrogen conditions. The
      NAD(P)H-dependent GDH of B. fragilis was confirmed to be most active under high
      ammonia conditions, but the NADH-specific GDH levels were increased by high
      peptide concentrations in the growth medium and not regulated by the levels of
      ammonia. Northern blotting analysis showed that gdhB regulation was at the
      transcription level, with a single transcript of approximately 1.6 kb being
      produced. GDH activity was demonstrated by zymography of the parental and
      recombinant enzymes. The recombinant GDH was NADH-specific and co-migrated with
      the equivalent enzyme band from B. fragilis cell extracts. The gdhB structural
      gene comprises 1335 bp and encodes a protein of 445 aa (49 kDa). Comparisons of
      the derived protein sequence with that of GDH from other bacteria indicated that
      significant sequence homology and conservation of functional domains exists with
      enzymes of Family I-type hexameric GDH proteins.

PMID- 9639937
TI  - Cyanide hydrolysis in a cyanide-degrading bacterium, Pseudomonas stutzeri AK61,
      by cyanidase.
AB  - The cyanide-degrading bacterial strain AK61 was isolated from waste water at a
      metal-plating plant. The isolated strain was characterized by Gram-staining,
      quinone analysis, fatty acid profile and the API 20NE identification system, and
      identified as Pseudomonas stutzeri. Whole cells were able to degrade cyanide
      rapidly in a 1 mM solution containing no organic substances, and produced ammonia
      as a product. The induction of the cyanide-degrading activity of P. stutzeri AK61
      did not depend on the presence of cyanide in the culture medium during growth.
      The cyanide-degrading enzyme was purified approximately 49-fold from a cell
      extract of P. stutzeri AK61. The enzyme had a K(m) of 1.7 mM for cyanide and a
      specific activity of 54.6 mumol ammonia produced min-1. The activity of the
      enzyme was optimal at 30 degrees C and pH 7.5. The results of SDS-PAGE, gel
      filtration chromatography and NH2-terminal amino acid sequence analysis of the
      enzyme indicated that the functional enzyme was an aggregated protein consisting
      of a 38 kDa polypeptide. Like cyanidase (cyanide dihydratase), it was shown that
      the enzyme catalysed the hydrolysis of cyanide to ammonia and formate.

PMID- 9639938
TI  - Distribution of 14C-labelled carbon from glucose and glutamate during anaerobic
      growth of Saccharomyces cerevisiae.
AB  - The distribution of carbon from glucose and glutamate was studied using
      anaerobically grown Saccharomyces cerevisiae. The yeast was grown on glucose (20
      g l-1) as the carbon/energy source and glutamic acid (3.5 g l-1) as additional
      carbon and sole nitrogen source. The products formed were identified using
      labelled [U-14C]glucose or [U-14C]glutamic acid. A seldom-reported metabolite in
      S. cerevisiae, 2-hydroxyglutarate, was found in significant amounts. It is
      suggested that 2-hydroxyglutarate is formed from the reduction of 2-oxoglutarate
      in a reaction catalysed by a dehydrogenase. Succinate, 2-oxoglutarate and 2
      hydroxyglutarate were found to be derived exclusively from glutamate. Based on
      radioactivity measurements, 55%, 17% and 14% of the labelled glutamate was
      converted to 2-oxoglutarate, succinate and 2-hydroxyglutarate, respectively, and
      55%, 9% and 3% of the labelled glucose was converted to ethanol, glycerol and
      pyruvate, respectively. No labelled glucose was converted to 2-oxoglutarate,
      succinate or 2-hydroxyglutarate. Furthermore, very little of the evolved CO2 was
      derived from glutamate. Separation of the amino acids from biomass by paper
      chromatography revealed that the glutamate family of amino acids (glutamic acid,
      glutamine, proline, arginine and lysine) originated almost exclusively from the
      carbon skeleton of glutamic acid. It can be concluded that the carbon flow
      follows two separate paths, and that the only major reactions utilized in the
      tricarboxylic acid (TCA) cycle are those reactions involved in the conversion of
      2-oxoglutarate to succinate.

PMID- 9639939
TI  - A novel quantitative mating assay for the fungal pathogen Cryptococcus neoformans
      provides insight into signalling pathways responding to nutrients and
      temperature.
AB  - Cryptococcus neoformans is a fungal pathogen that causes a lethal meningitis in
      immunocompromised individuals. Several factors are associated with virulence of
      this fungus, including its mating type; however, the mechanism by which mating
      type affects virulence is unknown. C. neoformans is a basidiomycete that exists
      in two mating types called a and alpha that can fuse to form an a/alpha dikaryon.
      A mating assay was developed that allowed a quantitative analysis of cryptococcal
      mating physiology. Interestingly, the efficiency of mating appeared to be
      dependent on temperature, being highest at 30 degrees C and almost completely
      absent at 37 degrees C. Thus, while mating type itself may be associated with
      virulence (which must occur at 37 degrees C), the ability to mate is probably not
      a virulence factor. Mating efficiency was increased by altering the carbon or
      nitrogen sources to give so-called starvation media. The addition of various
      drugs also seemed to alter the frequency of mating, depending on the composition
      of mating medium. The data suggested that cAMP, 8-bromo-cAMP and caffeine
      increased mating on starvation medium but only cAMP and 8-bromo-cAMP stimulated
      mating on rich medium; caffeine was unable to stimulate mating on rich medium.
      Aluminium fluoride, an activator of heterotrimeric GTP-binding proteins (G
      proteins), was also found to stimulate mating, suggesting the involvement of a G
      protein that may regulate the level of cAMP.

PMID- 9639940
TI  - Effects of relative humidity and applied force on atomic force microscopy images
      of the filamentous phage fd.
AB  - The filamentous phage fd was studied by both contact- and tapping-mode atomic
      force microscopy under conditions of controlled variations in relative humidity
      and changes in the applied tip force. By spin-coating freshly cleaved mica with
      phage containing solutions having very low salt content followed by rapid
      humidity control, stable and reliable sample preparation was achieved. The
      apparent height of the phage varied by about 10-fold with a quadratic dependence
      on the stabilized relative humidity, extrapolating to 73% of the accepted X-ray
      diffraction-based height at 0% relative humidity. The variation in measured
      height with relative humidity largely reconciles previous widely varying atomic
      force microscopy estimates of this dimension for the filamentous phage. Our
      finding that contact-mode images of phage are more difficult to analyze than
      those acquired in tapping mode are consistent with previously published results
      on other biological specimens such as DNA.

PMID- 9639941
TI  - Reconstruction of symmetry deviations: a procedure to analyze partially decorated
      F-actin and other incomplete structures.
AB  - The absolute value of individual differences (AVID) procedure is a method to map
      variations within images arising from deviations in symmetry. We devised this
      procedure to analyze images of actin filaments decorated with actin-binding
      proteins (ABPs). In three-dimensional maps of such actin complexes, ABPs often
      appear weak (i.e. they have low density) relative to actin. Because the 3D map
      represents an average taken over equivalent positions in the helix, the final
      density at the position of the ABP represents an average of the densities at all
      ABP sites. If there is either incomplete binding or a conformational variability
      of the bound ABP, the average density will be lowered. By the same argument, the
      variation of density at these sites will be increased. The aim of the AVID
      procedure is to calculate the density variations within partially decorated
      filaments and thereby attempt to locate the bound protein. We tested the AVID
      procedure with model data and then applied it to electron micrographs of F-actin
      decorated with an actin-binding domain of fimbrin known as N375 [Hanein et al.,
      J. Cell Biol. 139 (1997) 387-396]. The AVID maps have peaks at the site where
      N375 binds. Because it excludes the layer line data, the AVID procedure uses data
      that are independent of the data used for 3D reconstruction and difference
      mapping. It therefore provides an independent way to localize the bound subunit
      without the need for a map of undecorated actin. Moreover, the difficulties of
      scaling maps are minimized. This procedure could also be applied to structures
      with non-helical symmetry.

PMID- 9639942
TI  - Calcium antagonists, is there a real concern about safety?
AB  - Calcium antagonists are widely used in the treatment of arterial hypertension
      and, or in ischemic heart disease. During the last 3 years, controversial
      articles and editorials have been published concerning the potential risk of
      calcium antagonists in regard to mortality, cancer and haemorrhage. The
      information has been mainly derived from case-control studies. The major concern
      about such observational studies of treatment outcome is the large potential for
      systematic error to affect the results. However, overviews of controlled trials
      with calcium antagonists do not provide clear evidence of an effect of calcium
      antagonists on mortality, risk of cancer and risk of bleeding.

PMID- 9639943
TI  - Immunotherapy for allergic reactions.
AB  - In this review, hyposensitization or immunotherapy will be discussed. The
      earliest immunotherapy was applicated in allergic respiratory diseases such as
      asthma and rhinitis. The most important indication has become the treatment of
      hymenoptera allergy. Some less frequently indications are associated with drug
      allergy. Immunotherapy is most frequently indicated in IgE mediated diseases, but
      new applications for cell mediated reactions will be described. With the
      introduction of molecular biology in allergology new theoretical possibilities
      emerged: use of peptide antigens, recombinant allergens, anticytokines....
      Unfortunately, these newer approaches did not (yet) cause a breakthrough. The
      cost of these products will be a major draw back, even when ethical problems for
      using them on a larger scale will have been solved.

PMID- 9639944
TI  - Epidemiology as a tool for hospital infection control.
AB  - Epidemiology today studies the occurrence of health and disease and evaluates the
      global quality of health care, whereas it previously mainly consisted in the
      investigation of infectious outbreaks. This paper describes basic principles of
      descriptive and analytical hospital epidemiology, and focuses on the standardized
      and professional methodology used to manage nosocomial outbreaks. The basis for
      applied epidemiology for infection control purposes is surveillance. Computer
      technology permits data retrieval for detailed investigation by filtering the
      microbiology reports for specific data with nosocomial and epidemiological
      importance, so that expertise and organization of the microbiology laboratory
      have become key success factors for surveillance. In Belgium epidemiologists
      rarely, if ever, practice in hospitals as a separate discipline, although
      professional hospital epidemiology as part of infection control would be
      profitable for all. A debate is still to be held on how epidemiology should be
      organized in Belgian hospitals. It is generally accepted and provided by law that
      hospital hygiene physicians and nurses should perform epidemiological
      investigations and surveillance. However, the lack of professional training in
      epidemiology and insufficient resources constitute two major drawbacks.
      Microbiological typing techniques have become indispensable tools for
      epidemiology and should be accessible to every hospital infection control
      practitioner.

PMID- 9639945
TI  - [Inflammation phenomena in vasculitis: from immune complexes to less immune
      forms].
AB  - Immune complexes are involved in the pathogenesis of Henoch-Schonlein purpura,
      essential mixed cryoglobulinemia, hepatitis B-associated periarteritis nodosa and
      hypersensitivity vasculitis (related to infection or medications). ANCA's
      probably play a pathogenic role in Wegener's Granulomatosis, microscopic
      polyangiitis and renal-limited vasculitis. Pathologic responses of T-lymfocytes
      and granuloma formation have been demonstrated in temporal arteritis, Takayasu
      arteritis, Wegener's Granulomatosis, Churg-Strauss syndrome and Kawasaki
      syndrome. The eventual pathogenic role of AECA's is less clear, with the possible
      exception of rheumatoid arthritis and systemic lupus erythematosus. These four
      pathogenic factors are not mutually exclusive: several mechanisms may play in one
      disorder, as has been demonstrated for Wegener's Granulomatosis. From these new
      insights in the pathogenesis of vasculitis, new therapies with better efficacy
      and fewer side effects may arise.

PMID- 9639946
TI  - Neurological complications in critically ill patients; septic encephalopathy,
      critical illness polyneuropathy.
AB  - Septic encephalopathy and critical illness polyneuropathy are two syndromes,
      appearing at different stages in critically ill patients. Their aetiology is
      unclear, but many arguments seem to associate them with respiratory insufficiency
      in a context of systemic inflammatory response syndrome (S.I.R.S.) and multiple
      organ dysfunction syndrome (M.O.D.S.). Septic encephalopathy appears early in the
      course of sepsis, diagnosis is based on clinical picture and electro
      encephalogram. The exact pathogenesis is unclear. Prognosis is related to the
      underlying pathology, and treatment is supportive. Critical illness
      polyneuropathy is a predominantly motor axonal dysfunction, occurring in a
      setting of respiratory insufficiency, S.I.R.S., and M.O.D.S. A weaning problem
      often indicates the presence of critical illness polyneuropathy. Diagnosis is
      made on history, clinical picture and electromyographic studies. Indeed, motor
      and sensory conduction studies show a reduction of the amplitude of action
      potentials. In a later stage fibrillations and positive sharp waves emerge, with
      a further reduction of action potentials. Follow-up examinations reveal signs of
      axonal regeneration. The exact aetiology is unknown, but may be related to sepsis
      and M.O.D.S. Sepsis and M.O.D.S. are associated with the release of "mediator"
      substances, and somewhere in this cascade, there might be a toxin, influencing
      the nerve. A differential diagnosis with myopathy and neuromuscular transmission
      defects has to be made. Specific treatment is absent, and prognosis is related to
      the underlying pathology.

PMID- 9639947
TI  - The wide and deep excision of primary malignant melanoma: a dogma on the decline.
AB  - For years, a wide and deep excision of primary cutaneous melanomas has been
      recommended to achieve a better care and to decrease the risk of local recurrence
      of the disease. However, recent studies indicate that removal of peritumoral
      tissue beyond complete excision of the primary neoplasm does not decrease
      significantly the risk of local metastases. In addition, it confers no benefit to
      the patient survival.

PMID- 9639948
TI  - GB virus C: a novel pathogen or a curiosity for virologists?
AB  - The recently identified GB virus C is a flavivirus related to the hepatitis C
      virus. It appears quite prevalent in the general population and especially in
      individuals at risk of parenteral transmission. Many questions remain, most
      importantly the pathogenic role of the virus. It is unlikely that this virus has
      a major role in hepatic disease.

PMID- 9639949
TI  - [Nasal CPAP in sleep-related respiration disorders: patient profile, therapy
      compliance and influence of gas exchange and lung function pattern].
AB  - A survey performed in 100 CPAP users indicated that irritation of the face, a
      painful nose and nasal obstruction were among the most frequently mentioned
      complaints in chronic CPAP users. In 132 normocapnic SAS patients a significant
      improvement of PaO2 was shown, with a decrease of the alveolo-arterial oxygen
      difference. This improved gas exchange was parallelled by a significant increase
      in the FRC and TLC. Maybe a modulation in force of the respiratory muscles may be
      involved. These data were more pronounced in obstructive sleep apnea than in
      central sleep apnea. In 50 chronic CPAP users we could show a lower AHI
      immediately after CPAP withdrawal after a previous prolonged treatment. These
      findings may support the insufflation theory as a mechanism of action of CPAP.
      Traditionally, mechanical splinting of the upper airway has been considered as
      the dominant mechanism of action. Other mechanisms like changes in regulation of
      breathing and decrease of the pharyngeal edema may be involved as well.

PMID- 9639950
TI  - Tuberculous mediastinal lymphadenopathy.
AB  - We report about 2 cases of isolated mediastinal tuberculous lymphadenitis
      presenting without parenchymal infiltrates. Although rare, this mode of
      presentation reminds the clinician that tuberculosis has to be included in the
      differential diagnosis of mediastinal masses even in the absence of parenchymal
      lesion. Both cases illustrate the value of mediastinoscopic examination to assess
      the diagnosis.

PMID- 9639951
TI  - Experimental induction of renal lesions in chickens.
AB  - The present work was conducted to investigate the possibility of inducing renal
      lesions in chickens subcutaneously or orally inoculated with E. coli [E. coli
      O1K67(B12)], Staphylococcus aureus and Actinomyces pyogenes. The strains were
      previously isolated from the kidneys of broilers showing different pathological
      lesions. The gross lesions observed in the kidneys included enlargement,
      congestion, haemorrhagic spots in addition to dilatation and distension of the
      ureters. The microscopic lesions were mainly interstitial nephritis. The lesions
      were acute and changed gradually to subacute or chronic nephritis. The glomerular
      lesions were not common. The wall of the primary branches of the ureter and the
      ureters was heavily infiltrated with inflammatory cells, also granular and
      albuminous casts were seen in the renal tubules. The lesions were not related to
      the inoculated pathogen, although they were more severe in chickens inoculated
      with E. coli and Staph. aureus more than in Actinomyces pyogenes. Reisolation of
      the inoculated pathogens was more successful from the birds inoculated
      subcutaneously than from those infected orally.

PMID- 9639952
TI  - [Occurrence of bacterial infectious agents in pathologically/anatomically altered
      lungs of pigs and compilation of resistance spectra].
AB  - The goal of this work was to investigate the type and etiology of bacterial
      porcine pneumonia by analyses of autopsy findings made in the Tierarztlichen
      Ambulanz Schwarzenbek, Aussenstelle der Freien Universitat Berlin, and in the
      Institut fur Tiergesundheit, Milchhygiene und Lebensmittelqualitat der
      Landwirtschaftskammer Westfalen-Lippe in Munster in the years from 1991 to 1993.
      The evaluation of the results of the total 6560 autopsies (N = 6560) of pigs
      shows: 1. Pneumonia as the main diagnosis was found in 24.4% (n = 1599), as the
      second diagnosis in 14.3% (n = 941) of the sections. 2. Fattening pigs show signs
      of pneumonia (43.2% (n = 1096) vs. 27.8% (n = 706); N = 2540) more frequently
      than younger pigs. 3. The most frequently isolated etiologic agents from lung
      specimens (N = 2337) were Pasteurella multocida (49.3%; n = 1152), Actinobacillus
      pleuropneumoniae (5.4%; n = 125) and Bordetella bronchiseptica (5.3%; n = 124).
      4. With increasing age of the isolation rate of Pasteurella multocida (piglets [N
      = 210]: 21.4%, n = 45; fattening pigs [N = 652]: 61.8%, n = 403) and
      Actinobacillus pleuropneumoniae (piglets: 1.4%, n = 3; fattening pigs: 7.1%, n =
      46) increased while Bordetella bronchiseptica (piglets: 10.0%, n = 21; fattening
      pigs: 1.1%, n = 7) and Haemophilus parasuis (piglets: 3.8%, n = 8; fattening
      pigs: 0%, n = 0) were isolated at decreasing rates. 5. Most cultures of the lung
      samples (N = 2337) showed multiple infections (1087 = 54.2%). 6. The highest rate
      of single bacterial isolates was found for Pasteurella multocida (40.9%, n = 471,
      N = 1152) in relation to Haemophilus parasuis (30.9%, n = 11, N = 36),
      Actinobacillus pleuropneumoniae (24.0%, n = 30, N = 125), and Bordetella
      bronchiseptica (20.2%, n = 25, N = 124). 7. Less than 10% of the examined
      Pasteurella multocida, Actinobacillus pleuropneumoniae, Bordetella bronchiseptica
      and Haemophilus parasuis strains were resistant to tetracycline, oxytetracycline,
      enrofloxacin and kanamycin, but more than 55% were resistant to sulfonamides.

PMID- 9639953
TI  - [The problem of Q fever in zoo ungulates].
AB  - Antibodies to Coxiella burnetii were recorded from approximately 13% of 469
      ungulates which had been examined by means of micro-CFT (complement fixation
      test). Particular reference is made to a Q-fever situation in a musk ox herd. The
      results obtained from these investigations are likely to support the conclusion
      that latent Q-fever infection may be expected to occur in ungulates and to grow
      manifest in stress situations.

PMID- 9639954
TI  - [Evaluation of an intracutaneous test using a Sarcoptes mite extract solution
      (Acari: Sarcoptidae) as a method for detection of Sarcoptes mite-infested dogs].
AB  - Sarcoptes infestation in dogs, caused by Sarcoptes canis, is a relatively common
      disease in small animal practice. The parasites may induce severe allergic skin
      reactions. By means of clinical symptoms a presumptive diagnosis should be made.
      For ensurement detection of mites in skin scrapings is necessary, but it is not
      easy to find the parasites. Serodiagnostic methods are helpful to confirm the
      diagnosis. They indicate specific antibody (circulating IgE) titer.
      Intracutaneous test by using allergen extracts as possible third way of
      diagnostic methods was tested comparatively with the existing causaldiagnostic
      procedures in 45 dogs with suspected scabies. Preconditions of own examinations
      was mite antigen preparation. A mite extract solution of Sarcoptes suis was
      prepared and 0.1 ml were applicated intracutaneously. In 14 dogs (31.11%)
      allergic skin changes (Immediate reaction type 1) became apparent. The results
      were opposed to both other detection methods--skin scraping (4 positive
      findings/8.89%) and serodiagnosis (13 positive findings/30.77%).

PMID- 9639955
TI  - [Polymerase chain reaction (PCR) for detection of BLV provirus-- a practical
      complement for BLV diagnosis?].
AB  - A typical infection with bovine leukemia virus (BLV) induces a permanent antibody
      (Ab) response with high titers against BLV-antigens. In the last few years
      atypical courses of infection with low or transient BLV-Ab-titers or even lack of
      any detectable BLV-Ab-titers in animals with BLV-provirus integration have been
      described. This makes it difficult to eliminate BLV infection from herds using
      serological assays only. Whether or not polymerase chain reaction (PCR) is a
      useful tool to complement serological Ab-assays in BLV-eradication in herds was
      clarified in three ways: (i) different DNA-quick-preparations of blood were
      examined in nested PCR, (ii) cows of a BLV infected herd that was involved in a
      national eradication program were investigated for 6 months und (iii) BLV
      provirus-variants occurring in this herd were differentiated. The results show,
      that even by using PCR it was not possible to detect all infected animals all the
      time and that eradication of BLV from this herd was not completed in this short
      time. The PCR is useful for the investigation of herds and more sensitive than
      ELISA. PCR using LTR-primers (34 positive cattle) was more sensitive than PCR
      with env-primers (30 positive cattle). Using PCR 34 BLV infected cattle were
      detected of which only 21 reacted in ELISA. Restriction enzyme analysis or
      sequence analysis of PCR-amplificates allowed the detection of virus variants and
      conclusions about the way of infection. PCR should be used for BLV-eradication in
      cattle herds with low BLV-incidence, for the investigation of new outbreaks or
      tumor cases in long term BLV free herds and for investigation of breeding cattle.

PMID- 9639956
TI  - [Detection of Chlamydia psittaci infections in amphibians using an
      immunofluorescence test].
AB  - In amphibians, Chlamydia psittaci infections are known since 1982 as a fatal
      disease. Only documented in two amphibian species, the pathogen seems to be
      widespread in these coldblooded vertebrates. The detection of intracytoplasmatic
      inclusion bodies and following examinations (electronmicroscopy) were necessary
      for the postmortal diagnosis. In 26 amphibians (3 species) a specific
      immunological testkit (immunofluerescence test) have been used. In 18 cases a
      positive result was found. This is the first report about using an IFT for the
      detection of Chlamydia psittaci in amphibians. Two new host species for this
      pathogen were found, one bufonid anuran (Bufo maculatum) and the new Pachytriton
      sp.

PMID- 9639957
TI  - Pleural fluid: accuracy of computed tomography in differentiating exudates from
      transudates.
AB  - PURPOSE: To determine the accuracy of computed tomography in differentiating
      pleural exudates from transudates when reviewed subjectively by two experienced
      radiologists in a community hospital. METHODS: Computed tomography scans of 55
      consecutive patients who had a thoracenteses within 10 days of the study were
      retrospectively reviewed independently by two experienced staff radiologists.
      They were asked to evaluate subjectively parietal pleural thickness (anterior,
      lateral, posterior), attenuation of extra-pleural fat, and categorize pleural
      fluid as loculated or free flowing. Radiographic findings were correlated with
      biochemical results of thoracentesis (Light's criteria) to assess the accuracy of
      computed tomography in differentiating pleural exudates from transudates.
      RESULTS: For the diagnosis of an exudate, pleural thickening alone had the best
      sensitivity and specificity (50%, 100%, respectively) with an accuracy of 55%.
      CONCLUSION: Subjective evaluations for increased pleural thickness have a high
      accuracy for diagnosing pleural exudates.

PMID- 9639958
TI  - Atorvastatin (Lipitor).

PMID- 9639959
TI  - As life ebbs, so does time to elect comforts of hospice.

PMID- 9639960
TI  - Physician liability for suicide of noncustodial patient.

PMID- 9639961
TI  - Regarding: "Trends in the incidence of upper extremity soft tissue malignancies:
      a 40-year review of the Connecticut State Tumor Registry".

PMID- 9639962
TI  - Burdensome Medicare guidelines.

PMID- 9639963
TI  - Leg edema secondary to bladder distention.

PMID- 9639964
TI  - How to evaluate national suicide programs?

PMID- 9639965
TI  - Hotlines and mental health services.

PMID- 9639966
TI  - Arranging the death of a king.

PMID- 9639967
TI  - The posttotalitarian pattern of suicidal behavior: impact on youth.

PMID- 9639968
TI  - Letter across the Pacific.

PMID- 9639969
TI  - A clinical-psychological approach to suicidal behavior in depression from Moscow.
AB  - This contribution strives to familiarize Western readers with the theoretical
      concept of suicidal behavior which was developed at the Department of Suicidology
      of Moscow Psychiatric Research Institute and has been in use there for the last
      two decades. In describing this approach the paper concentrates on what
      differentiates it from traditional Western management without making value
      judgments about either approach. Such an account of the concept and its
      development will hopefully afford the reader an opportunity to arrive at his or
      her own conclusions regarding its clinical value.

PMID- 9639970
TI  - Empowered consumers and telephone hotlines.
AB  - Today health-care budgets are rapidly being cut and services streamlined.
      Volunteers and nonprofit agencies have been commissioned to take on part of the
      burden. Currently they are expanding and reorganizing their services to meet the
      new demand. Telephone crisis lines, in particular, have the potential to take on
      a large share of consumer needs--they are always available and turn no one away.
      Unfortunately, crisis lines have their own set of problems. Although the bulk of
      work is performed by volunteers and represents a minimum of expense, the
      clientele is varied, the workload unpredictable. Staff at the line need to
      balance the needs of their regular callers with crisis calls and their volunteer
      needs by establishing comprehensive policies. This article looks at just a few of
      the challenges these lines face, and attempts to analyze the options, keeping the
      rights of modern consumers in mind.

PMID- 9639971
TI  - Suicides in Hong Kong and Australia.
AB  - Although the suicide rate for both Hong Kong and Australia was about 12 per
      100,000 in 1994, the age- and gender-specific rates, methods of suicide, and time
      trends vary greatly for these two places. This paper explores the possible
      social, economic, and cultural background to explain this discrepancy. We used
      the official suicide death statistics of Hong Kong and Australia for the period
      1984-1994. We calculated age-standardized suicide rates in order to take into
      account the differences in the age composition between the two countries and
      years. We employed a log-linear (Poisson) model to detect the age- and gender
      specific trends, and to determine whether there were specific age or gender
      groups whose suicide behavior had changed significantly between 1984 and 1994.
      Hong Kong experienced a slight increase in suicide rate for both genders in the
      years 1984-1994, whereas Australia experienced a cubic trend for both genders
      during the same period and a rise in suicide rate in recent years. The suicide
      rate in Hong Kong increased with age, with a sharp increase (nearly four times
      the average) among the group aged 75 or over. A relatively low gender ratio
      (male:female) was also observed in Hong Kong, whereas in Australia there was not
      much difference in suicide rates among all age groups, though the suicide rate of
      the group aged 75 or over was 1.2 times the average. The gender ratio in
      Australia was higher, and the male suicide rate was four times higher than that
      of females. The Hong Kong suicide rate in females was twice that of Australia,
      whereas the Hong Kong male suicide rate was about half that of Australia. Jumping
      and hanging were the most common methods of suicide in Hong Kong, accounting for
      more than 80% of all suicide deaths. Poisoning (including gas poisoning) was the
      most common method used in Australia, with firearms being more common among young
      males. Australia had a higher years of potential life lost (YPLL) than Hong Kong
      because of the higher suicide rate among young males (aged 15-24). The high
      suicide rate among the elderly in Hong Kong raises the possibility that medical
      and social support to the elderly could be enhanced. The high female suicide rate
      in Hong Kong could be related to workload, responsibility, and expectations. The
      high suicide rate in Australia among males aged 15-24 was disturbing.
      Availability of the suicide methods is certainly one explanation for the
      difference in suicide methods used in Hong Kong and Australia.

PMID- 9639972
TI  - A study of elderly suicides in Hong Kong.
AB  - Hong Kong has one of the highest rates of suicide among the elderly in the world.
      Most of the existing suicide prevention programs have had very little effect on
      the elderly, who rarely utilize these programs. This study aims to help in
      understanding the problem, so that effective prevention can be provided to this
      high-risk group of suicidal people. Specifically, the study (1) describes the
      characteristics of the suicidal elderly, (2) investigates the reason(s) why the
      elderly are in distress and become suicidal, and (3) formulates a policy and
      service model to reach the elderly high-risk group. This research project
      involves secondary data analysis. Police records on elderly suicide cases in 1992
      were scrutinized to find out the major reason(s) for fatal death in the elderly.
      Our study points out those districts that are more crowded and have fewer medical
      and social facilities tended to have higher suicide rates. Most of the deaths
      occurred at home or nearby, and the suicidal elderly were alone before their
      death. The majority of elderly suicide victims suffered from chronic diseases.
      Very few of them, however, were totally dependent: About 40% of the cases had
      consulted medical practitioners, and 27% had consulted psychiatrists within one
      month before their deaths. Close to 70% of the cases had indicated to family
      members or other their suicidal thoughts, and many of them had revealed numerous
      suicidal indications. Both policy and practice issues are discussed in light of
      the findings.

PMID- 9639973
TI  - Attempted suicides in Ankara in 1995.

PMID- 9639974
TI  - [Evaluation of bacteriological research data and laboratory symptoms of infection
      in the diagnosis of congenital and acquired infections].
AB  - The predisposition of the newborns to contract infections diseases is dependent
      upon the limited efficiency of their immune mechanisms. Congenital infections
      amount to 5.7% in the research material, and the acquired infections 1.15%. The
      isolation of the microorganism is the basis for treating infections-the profiles
      of the pathogenic bacterial in flora were subjected to analysis. Im generalised
      infections Stafphylococcus epidermidis makes 56.6% and E. Coli accounts for 87.5
      of the infections of the urinary system. In our research the late sepsis and
      pneumonia are more frequently the result of the hospital infection (14.2%) in the
      cases of congenital infections-pneumonia and the infection of the urinary system
      (72%). Hematologic indicators such as: leucopenia, thormbocytopenia, I/T are
      distinct infection markers (those were found in 31% of the cases). The CRP
      protein shows the lowest values in congenital infections, still monitoring its
      level is useful for assessing the effectiveness of the undertaken antybacterial
      treatment. The newborns of male sex (58%) more often prone to infection.
      Pneumonia is the manifestation pertaining to an organ in 70% of congenital
      infections, the infection of urinary system amounts to 17.1%.

PMID- 9639975
TI  - The concentration of cotinine in urine, colostrum and amniotic fluids within the
      system mother-baby.
AB  - The findings obtained by the authors of the thesis submit the new cognitive
      values to the diagnosis of pathology of pregnancy i.e. the influence of nicotine
      on the organisms of a mother and a new-born child, estimated by the assay of
      cotinine, the most important metabolite of nicotine. The authors lay a particular
      stress on the "colostrum-milk way" in the mother-child relationship and this is
      that needs to be emphasized in this thesis.

PMID- 9639976
TI  - The average quantitative concentration of cotinine within the system pregnant
      woman-baby.

PMID- 9639977
TI  - [Surgical treatment of uterine leiomyomas in infertile patients].
AB  - Retrospective analysis of the results of operative treatment for uterine
      leiomyomas was carried out. Our screening included the total of 186 patients. One
      hundred and eight women responded to the questionnaire /58%/. Respondens were
      treated for sterility in the period between 1990-1995. Successful operative
      treatment, expressed as pregnancy rate reached 29.7%.

PMID- 9639978
TI  - [Trinucleotide repeats polymorphism of the androgenic receptor gene in the
      detection of carriers of androgen insensitivity syndrome].
AB  - Androgen insensitivity syndrome (AIS) is caused by mutation in androgen receptor
      (AR) gene. This phenomenon leads to the defect of the virilization of the
      external genitalia and is one of the causes of human male pseudohermaphroditism.
      Molecular diagnosis of AR gene mutations is very complex because of heterogeneity
      of AR mutations. AIS is X-linked recessive trait and therefore the simple
      diagnosis of AIS carriers is a very important problem. Detection of AIS carriers
      by using the analysis of CAG repeating sequence polymorphism of exon 1 or AR gene
      is reported.

PMID- 9639979
TI  - [The significance of cardiography in the diagnosis of cardiac ectopia of the
      fetus].
AB  - Retrospective analysis of echocardiographic examinations of 7 fetuses with
      ectopia cordis was presented. The majority of abnormalities were found in low
      risk pregnancies. There was only one case of isolated ectopia cordis with normal
      heart anatomy and no extracardiac malformations. There was no survival.
      Theoretically the prenatal diagnosis of isolated ectopia cordis may help to
      choose the proper term, place and method of delivery and also to plan the optimal
      care of newborn. Parents should be counseled about the prognosis in such cases,
      at the tertiary center, after detailed fetal echocardiography.

PMID- 9639980
TI  - [The analysis of factors which affect qualification of pregnant women as cord
      blood donors].
AB  - Authors' analysis refers to reasons for which some women did not meet criteria
      for the programme of collection of cord blood by The Cord Blood Bank in Warsaw.
      The main reasons were: 1) reactivation of infection with CMV virus, 2)
      complications of delivery and 3) technical problems. We present also preliminary
      results of blood tests aimed at identification of some viral (hepatitis B and C,
      HIV, CMV), bacterial (Treponema pallidum) and protozoal infections (Toxoplasma)
      in the selected group of pregnant women.

PMID- 9639981
TI  - [Ultrasound diagnosis of four fetuses with Fraser syndrome during pregnancy].
AB  - The authors present results of sonography analysis of four fetuses with Fraser
      syndrome. First woman had prenatal diagnosis by ultrasounds and ascites of fetus
      with polyhydramnion were diagnosed in two of her successive pregnancies. The
      second pregnant woman was observed by ultrasound and lack of kidney was detected.
      The third pregnant one was diagnosed at first trimester of pregnancy and results
      of sonography examination were at norm. After delivery, Fraser syndrome in all of
      these children was diagnosed. Findings on sonography included: ascites of fetus,
      polyhydramnion, hydrocephalus and nonvisualization of kidney. Sonography is more
      efficient in the diagnosis of Fraser syndrome in a fetus whose parents had had a
      previous affected child because of diverse anomalies were observed.

PMID- 9639982
TI  - Emergency medicine in the problem-based learning curriculum.

PMID- 9639983
TI  - Common sports injuries seen by the primary care physician. Part II: Lower
      extremity.
AB  - Sports medicine is the science of caring for the medical and surgical needs of
      athletes and their injuries. Injuries of the upper extremity were dealt with in
      Part I in a previous article. Part II deals with injuries of the lower extremity.
      Trochanteric bursitis and hamstring strains are treated with rest,
      rehabilitation, and correction of training errors. Patellofemoral pain syndromes
      require accurate diagnosis and usually a rehabilitative program. Injuries to the
      medial collateral ligament are very common, but can be associated with tears of
      the meniscus and cruciate ligaments. The latter two often require surgical
      intervention. Ankle sprains are graded by severity. The most severe can result in
      chronic pain or instability, but most respond well to functional bracing and
      progressive return to activity.

PMID- 9639984
TI  - 10 common medicolegal questions on HIV infection.
AB  - As the HIV pandemic continues, physicians will increasingly face both medical and
      legal questions when caring for these patients. Using a question and answer
      format, we provide in this paper, a guide to physicians in Hawaii on the
      medicolegal issues surrounding HIV infection.

PMID- 9639985
TI  - Fat chance of immunomodulation.

PMID- 9639986
TI  - Tumour immunology: false hopes--new horizons?

PMID- 9639987
TI  - Pediatric rheumatology: autoimmune mechanisms and therapeutic strategies.

PMID- 9639988
TI  - Innate T-cell immunity to nonpeptidic antigens.

PMID- 9639989
TI  - CD1-restricted T cells and resistance to polysaccharide-encapsulated bacteria.

PMID- 9639990
TI  - Collagen receptor signalling in platelets: extending the role of the ITAM.

PMID- 9639991
TI  - Enkelytin and opioid peptide association in invertebrates and vertebrates: immune
      activation and pain.

PMID- 9639992
TI  - Gap junctions: a novel route for direct cell-cell communication in the immune
      system?

PMID- 9639993
TI  - Preferential expression of TCR V alpha regions in CD4/CD8 subsets: class
      discrimination or co-receptor recognition?

PMID- 9639994
TI  - The role of endosomes and lysosomes in MHC class II functioning.

PMID- 9639995
TI  - Immune modulation by zinc: clues from immunoglobulin structure and function.

PMID- 9639996
TI  - Genetics of type I diabetes.

PMID- 9639997
TI  - The role of dendritic cells in contact hypersensitivity.

PMID- 9639998
TI  - An experimental study of the esthetic effect of facial profiles.
AB  - In this study good-looking "male" and "female" as well as ugly facial profiles
      were shaped by 104 lay persons using an especially constructed device according
      to specific instructions. These profiles were photographed and subsequently
      evaluated using a series of parameters from soft tissue profile analyses.
      Although some significant mean value differences were found between the good
      looking and ugly profile variants, they were not substantial. In contrast,
      markedly significant differences were revealed between the variances of all
      variables. In some instances the variance of the ugly profiles was more than 3 to
      4 times higher than that of the good-looking profiles. These findings were
      convincingly confirmed when statistical distribution of the data was established
      and compared. This implies that perception of beauty is associated with
      regularity of facial features and is conveyed by measurement values which are
      located close to the mean. Ugliness is associated with extreme deviations from
      the latter in either direction. Apart from the facial proportions, the degree of
      convexity or concavity of facial profile and their sequence seem to be important
      for the esthetic effects. "Male" profiles in contrast to "female" profiles
      exhibited more conspicuous facial features such as pronounced convexity and
      concavity.

PMID- 9639999
TI  - Class II correction with magnets and superelastic coils followed by straight-wire
      mechanotherapy. Occlusal changes during and after dental therapy.
AB  - The investigation comprised 18 consecutively selected patients, mean age 14.7
      years at the start of treatment, with Class II malocclusion, deep overbite and
      space deficiency in the maxillary arch. The first phase of the treatment
      consisted of 6 months simultaneous distal movement of maxillary first and second
      molars with repelling samarium-cobalt magnets on one side and a superelastic
      nickel-titanium coil on the contralateral side together with an anterior
      biteplane to achieve bite opening. For the second phase of the treatment, a
      straight-wire appliance was used for an average treatment time of 1.3 years.
      Lateral head radiographs and dental casts were available at the start of
      treatment, after molar distalisation, at the end of treatment and 1 year post
      treatment. The treatment resulted mainly in dental changes. The dental Class II
      molar relation was corrected to Class I by bodily distal movement of maxillary
      molars and by mesial movement of the mandibular molars. The correction of molar
      relation was significantly greater on coil sides than on magnet sides, mean 3.4
      mm, and 3.0 mm, respectively. Despite anchorage loss associated with the
      maxillary molar movement, i.e. mesial movement of the maxillary incisors (mean
      1.8 mm), the net overjet was reduced, mean 2.5 mm, by the use of Class II
      elastics. The average net improvement of bite opening was 2.6 mm, mainly due to
      extrusion of mandibular and maxillary molars. During the 1-year post-treatment
      period no significant dental or skeletal changes were found. The long-term
      implications of the treatment results need further consideration.

PMID- 9640000
TI  - Frictional forces when rectangular guiding arches with varying edge bevel are
      employed.
AB  - In orthodontic treatment employing arch guided tooth movement, rectangular wires
      are usually used to achieve three-dimensional controlled tooth movement. In the
      intention to optimize sliding mechanics and to improve the comfort of patients,
      edge beveled rectangular orthodontic wires are offered by different
      manufacturers. The objective of the study presented was to investigate the
      influence of differing but defined wire roundings on sliding mechanics of canine
      retraction. Employing the 0.018" slot system, 0.016" x 0.022" standard steel
      wires (Remaloy and Remanium, Dentaurum Comp.) were tested. Force loss due to
      friction during canine retraction was determined using the Orthodontic
      Measurement and Simulation System (OMSS). In the arch guided distalization of
      canines, the average loss of force caused by friction was determined to be
      approximately 50%. Comparing wires with different edge bevel, the rounded wire in
      contrast to the wire with sharpest edge configuration results in a reduction of
      friction. Even a moderate wire rounding of the 0.016" x 0.022" steel wire results
      in about 10% reduction in frictional losses. However, dynamic analysis of tooth
      movement with the OMSS shows that there is no further improvement of sliding
      mechanics using wires with edge bevel exceeding the standard rounding of
      rectangular wires. In contrast, a strong edge bevel may result in a considerable
      loss of leveling.

PMID- 9640001
TI  - Condylar restoration after early TMJ fractures and functional appliance therapy.
      Part I: Remodelling.
AB  - The aim of this study was to measure quantitatively and to analyze the process of
      condylar restoration during and after functional appliance therapy with an
      activator in children and juveniles who had sustained condylar fractures. Spiral
      computed measurement of condylar morphology was performed in order to quantify
      the association described in the literature between condylar remodelling and age
      as well as certain types of fracture. Nineteen patients with an average age of
      13.4 years, who had sustained a functionally treated unilateral condylar fracture
      4.9 years earlier on average, were included in the present study as the follow-up
      group. Twenty patients, who had sustained a unilateral fracture at an average age
      of 8.1 years and had been treated functionally for 6 to 8 months, formed the
      treatment group. The condylar dimension and the condylar neck length of the
      ipsilateral and of the contralateral temporomandibular joints were measured from
      the axial and parasagittal reconstructions and were compared on the basis of sex,
      age and fracture type. The mediolateral condylar dimension of the follow-up group
      showed a sex-specific difference of 0.2 cm on the contralateral side and 0.4 cm
      on the ipsilateral side. The fracture side condyle indicated a relative
      mediolateral decrease of 4.2% and an anteroposterior increase of 12.6%.
      Shortening of the condylar neck and excessive bony overgrowth were found to occur
      more often in fractures with displacement and in low fracture types. The "10
      plus" subgroup at time of trauma showed a significantly greater variation and
      greater differences in mediolateral and anteroposterior condylar dimension than
      the younger patients.

PMID- 9640002
TI  - Evaluation of the profile line in prognathic patients in the Saxony-Anhalt region
      of Germany.
AB  - The aim of the present study was to investigate the soft-tissue morphology and
      profile line of prognathic patients in the Saxony-Anhalt region of central
      Germany. To this effect, the profile photographs and lateral cephalograms taken
      at treatment start for 34 adults (17 female patients, mean age: 22.6 years; 17
      male patients; mean age: 23.2 years), Class III subjects who had not undergone
      orthodontic treatment, were measured and, by means of statistical analysis, the
      findings were compared with those of an age-matched control group (17 female
      subjects, mean age: 21.4 years; 17 male subjects, mean age: 23.8 years). Patients
      with Class III anomalies had a significantly longer and thinner lower lip and a
      smaller lower subnasal angle than the control subjects. The lower face was
      markedly enlarged. Furthermore, the osseous profile line was significantly
      flatter and the soft-tissue convexity was considerably reduced compared with the
      control group. Hence the prognathic patients of central Germany manifested
      typical features of the prognathic profile line. To elucidate typical regional
      features, further comparative studies are required.

PMID- 9640003
TI  - Incisor torque by means of a modified Teuscher activator. Three case reports.
AB  - It is generally accepted that in the treatment of Class II, 1 malocclusion
      classical activators may tip the upper incisors considerably. In comparison, in
      the cases described, an even better torque control was obtained. It has been our
      clinical experience that with the modified Teuscher activator it is possible to
      control upper incisor inclination and in some cases it is even possible to induce
      active palatal root torque. The appliance is relatively comfortable with good
      vertical retention even without headgear.

PMID- 9640004
TI  - Oculo-facio-cardio-dental (OFCD) syndrome.
AB  - The association of facial dysmorphy, congenital cataracts, microphthalmia, heart
      disease, and dental radiculomegaly is very rare. We describe a girl with atrial
      septal defect, unilateral congenital cataract, unilateral microphthalmia,
      radiculomegaly of incisor and canine teeth with open apices and other dental
      crown anomalies. This combination of symptoms clearly represents a distinct
      syndrome and has recently been described as oculo-facio-cardio-dental (OFCD)
      syndrome.

PMID- 9640005
TI  - Orthodontic treatment of a Class II, 1 malocclusion including extractions of the
      4 first molars. Case report.
AB  - Orthodontic treatment of a Class II, 1 malocclusion in a 13-year-old boy is
      demonstrated. The first molars were extracted and an edgewise appliance was used.

PMID- 9640006
TI  - Sexually transmitted diseases and adolescents.

PMID- 9640007
TI  - Quality parental decision making and distress.
AB  - The purpose of this study was to test three hypotheses in the context of
      parenting an adolescent: (1) socioeconomic status (SES), parental gender, marital
      status, and age of parent will be predictors of quality decision-making for
      parents of adolescents; (2) as predispositional and situational distress
      increase, quality decision making among these parents will decrease; and (3)
      predispositional distress will be as strong a predictor for quality decision
      making as situational distress. The sample included 123 parents of adolescents
      ages 13 to 19 years. SES was the only significant predictor (11%) for parental
      decision making; the higher the SES, the more quality in decision making
      reported. Moderate negative correlations were obtained between predispositional
      distress and quality decision making and situational distress and quality
      decision making. Both predispositional distress and situational distress
      contributed equally as predictors of quality decision making.

PMID- 9640008
TI  - The Hispanic teen mother's origin of birth, use of prenatal care, and maternal
      and neonatal complications.
AB  - The purpose of this study was to describe and compare differences in
      demographics, prenatal care use, and pregnancy, labor, postpartum, and neonatal
      complications for 129 pregnant Mexican-American adolescents who were either born
      in the United States or born in Mexico. A significant finding was that 25% of the
      teens, regardless of origin of birth, received either inadequate or no prenatal
      care. The findings of this study will be useful to clinicians providing health
      care for Hispanic teens and for administrators and policy makers who affect the
      types of health care and education available to these young mothers.

PMID- 9640009
TI  - Reducing teenage and unintended pregnancies through client-centered and family
      focused school-based family planning programs.
AB  - Achievement of the national health goal to reduce teenage and unintended
      pregnancies through family planning requires a holistic approach to primary
      prevention. Building upon Rogers' Science of Unitary Human Being, Orem's Self
      Care Theory, and Rosenstack's Health Belief Model, a client-centered and family
      focused school-based family planning program is proposed as a means to achieve
      the health goal. FNPs play a pivotal role in development and successful
      implementation of such a program.

PMID- 9640010
TI  - The interpretation of infant pain: physiological and behavioral indicators used
      by NICU nurses.
AB  - The purpose of this descriptive study was to identify the indicators used by
      neonatal nurses to interpret the experience of pain in infants in a Neonatal
      Intensive Care Unit (NICU). A sample of 72 NICU nurses completed a structured
      questionnaire to identify the physiological and behavioral indicators they used
      to interpret the experience of pain in the infants entrusted to their care. The
      10 pain indicators used by more than 50% of the nurses, listed in decreasing
      order of frequency, were: fussiness, restlessness, grimacing, crying, increasing
      heart rate, increasing respirations, wiggling, rapid state changes, wrinkling of
      forehead, and clenching of fist. These findings are consistent with existing
      literature, are compatible with the stress cues identified in Als' Synactive
      Theory of Development, and lend support to the use of such measures for the
      assessment of infant pain.

PMID- 9640011
TI  - Discharging ventilator-dependent children: a continuing challenge.
AB  - Preparation of ventilator-dependent children, their families, the health care
      system, and communities for community-based care has presented many challenges
      over the past two decades. This article reviews some of the challenges that have
      been resolved by interdisciplinary discharge planning, discharge protocols, case
      management approaches, and collaborative care. Unresolved challenges continue to
      prevent children with special health care needs (CSHCN) from being served
      adequately by the health care system, the legal system and the community in this
      era of cost containment. Current literature, existing research and clinical
      observation were used to develop nursing implications and recommendations for
      continued research.

PMID- 9640012
TI  - Community child health nursing: a New Zealand experience.

PMID- 9640013
TI  - The nurse's role in the prevention of child abuse and neglect: Part II.

PMID- 9640014
TI  - I.V. HOUSE: pediatric nurses contribute to refinement of i.v. protector.

PMID- 9640015
TI  - [Evaluation of visual evoked potentials in partial optic nerve atrophy].
AB  - PURPOSE: Parameters of visual evoked potentials in partial optic nerve atrophy in
      different aetiology were studied. MATERIALS AND METHODS: The study involved 48
      patients (68 eyes) with partial optic nerve atrophy from neuritis, toxic,
      arteriosclerosis and trauma. The tests of visual evoked potentials were performed
      by the use of UTAS E-1000 computer system in all patients with the use of pattern
      and flash stimulation. RESULTS: Amplitude of all waves were reduced in 74%
      patients using "pattern" and in 61% patients using "flash" stimulation. Latency
      of wave P2 was delayed in all patients with optic nerve atrophy from
      arteriosclerosis. Latency of P100 wave and N1 wave were not delayed in patients
      with optic nerve atrophy from toxic neuropathy. CONCLUSIONS: Estimation of
      latency of the VEP may be useful in diagnosis of the partial optic nerve atrophy.
      Variety of records of VEP indicate different degree of disturbances of nerve
      conduction.

PMID- 9640016
TI  - [The condition of the posterior capsule in pseudophakic retinal detachment].
AB  - PURPOSE: Analysis of condition of posterior capsule in pseudophakic retinal
      detachment. MATERIAL AND METHODS: 37 pseudophakic eyes of 35 patients with
      retinal detachment were examined. The condition of posterior capsule and the time
      when retinal detachment was observed were analysed. CONCLUSION: Disruption of the
      posterior capsule as a complication of cataract surgery was associated with a
      significant elevated risk of retinal detachment. Uncomplicated posterior capsule
      prevented acid from vitreous delayed retinal detachment, but is not eliminated,
      especially in risk factor cases.

PMID- 9640017
TI  - [Late effects after anterior intraocular lens implantation].
AB  - MATERIAL AND METHODS: During ten years, 890 operations of cataract with anterior
      chamber intraocular lens implantation were performed. TWO GROUPS OF EYES WERE
      OBSERVED: Eyes after planned intracapsular cataract surgery and eyes in which
      intraoperative complications occurred making impossible to apply posterior IOL.
      PURPOSE: To evaluate late complications and functional status of the eye.
      RESULTS: Our results indicate that anterior chamber intraocular lens implantation
      yields in many cases good visual acuity and, although not free of complications,
      is a safe procedure.

PMID- 9640018
TI  - [Corneal astigmatism after trabeculectomy].
AB  - PURPOSE: The aim of the present study was to investigate the effect of
      conventional and mitomycin trabeculectomy on the corneal astigmatism. SUBJECT AND
      METHODS: Measurements with the use of computer-assisted videokeratography (Eye
      Sys) were performed in 34 glaucoma patients who underwent trabeculectomy. Color
      coded topography maps were analyzed to obtain astigmatic data. RESULTS: The mean
      surgically-induced astigmatism in conventional trabeculectomy group was 2.2 D and
      in the mitomycin group 4.0 D, 1 day post-op, 1.3 D and 3.0 D after 10 days and
      0.4 D and 1.1 D after 3 months, respectively. CONCLUSION: There was an apparent
      correlation between the amount of induced astigmatism and the use of mitomycin.
      This may be related to the impaired healing process of trabeculectomy wound and
      lower intraocular pressure in the mitomycin group.

PMID- 9640019
TI  - [Evaluation of the rate of ophthalmologic complications of insulin-dependent
      diabetes mellitus in children and adolescents].
AB  - PURPOSE: To detect very early changes of the visual organ among 156 young
      patients with diabetes mellitus. MATERIAL AND METHODS: Beyond the traditional
      ophthalmological examination, the fluorescein angiography and electroretinography
      were performed. RESULTS: On the whole, the changes were confirmed in 56 children
      (35.8%). Diabetic retinopathy was observed in 24 cases (15.4%), changes of the
      lens revealed in 52 children (33.3%). Among 40 children examined with electro
      retinography 25 had decreased amplitude and prolonged latency of oscillatory
      potentials. CONCLUSIONS: Fluorescein angiography is the more sensitive method of
      examination than routine ophthalmoscopy. Electro-retinography seems to be
      important in the diagnosis of early changes of diabetic retinopathy.

PMID- 9640020
TI  - [Changes in the corneal curvature in soft contact lens users].
AB  - PURPOSE: This study was designed to show the corneal topography changes induced
      by contact lens use. MATERIAL AND METHOD: The corneal topography has been
      examined in 19 contact lens users (37 eyes). RESULTS: The mayor changes in
      topography have been found between 6th and 18th week after stopping the contact
      lens wearing.

PMID- 9640021
TI  - [Examination of ocular lesions in drug abusers in Poland].
AB  - The authors present ocular symptoms in 116 drug abusers. They have observed optic
      atrophy and defects in visual field in 9 cases, reduced convergence in 8 cases,
      slow pupillary reaction in 9 cases, ptosis in 3 cases, nystagmus in 2 cases,
      retinal haemorrhages in the nerve fibre layer in 2 cases, myopia in 45 cases and
      blepharoconjunctivitis in most of cases. The authors want to indicate the
      principal ocular signs in drug abusers in our country.

PMID- 9640022
TI  - [Bilateral isolated posterior scleritis].
AB  - A case of 44-year-old man is presented with no simultaneous bilateral posterior
      scleritis with amelanotic chorioidal mass initially diagnosed as intraocular
      tumor. The patient showed the features of nodular posterior scleritis without
      associated systemic disease. The case presented symptoms of severe eye pain,
      unilateral proptosis, hyperemia and dilatation of scleral, episcleral and
      conjunctival vessels. Diagnosis was made on the basis of B-scan ultrasonography.
      Differential diagnosis excluded melanoma malignum chorioideae, orbital
      cellulitis, Graves ophthalmopathy, orbital cellulitis, cavernous sinus thrombosis
      and carotid-cavernous fistula. The patient did not respond well to systemic
      steroids given in high doses and during slow tapering at the dosage of 30 mg
      prednisone once per day the symptom of uveal effusion syndrome occurred. After 10
      months of steroid therapy the signs of disease like mild hyperemia and tenderness
      were still present. The adjunction of cyclosporin improved the disease and caused
      the remission.

PMID- 9640023
TI  - [Ocular manifestations of the HELLP syndrome].
AB  - A 23-year old female patient diagnosed as HELLP syndrome (H-hemolysis, EL
      elevated liver enzymes, LP-low platelets) was admitted during her 34th week of
      first pregnancy. After caesarean section she received hypotensive and
      anticoagulant treatment and blood transfusion. Her general condition was
      improved. The ocular manifestations (i.e. blurred vision, retinal oedema nad
      hemorrhages) were seen on the 10th postpartum day in both eyes. The ocular
      changes disappeared 4 month later.

PMID- 9640024
TI  - [Pleoptic therapy in anisometropic and strabismic amblyopia].
AB  - The study aims at describing the current trends in pleoptic treatment with a
      special attention paid to the practised exercises. On the basis of literature a
      short review of the pathogenesis of amblyopia with or without strabismus is
      presented. The need for careful choice of the treatment according to specific
      conditions in each subject is emphasised. The importance of active pleoptic
      therapy in cases with or without strabismus is particularly pointed out. In
      anisometropia contrast sensitivity is decreased, differentiation of optotypes put
      in line and shape differentiation are worsened, ability to discern figures and to
      accommodation are impaired. Amblyopia with strabismus leads to decrease in space
      orientation ability, impairment in following movement, prolongation of saccadic
      movement and of eye-hand coordination time. The types of visual dysfunction
      mentioned above determine the exercises which should be recommended in a given
      case. Examples of exercises are presented and the range of improvement possible
      to achieve is documented.

PMID- 9640025
TI  - Treatment of the wounded at Chipyong-ni.

PMID- 9640026
TI  - Utilization of combat stress control detachments.

PMID- 9640027
TI  - Subject: military disaster medicine.

PMID- 9640028
TI  - Mental health nursing support during Operation Sea Signal: Cuban/Haitian
      humanitarian mission.
AB  - Joint military humanitarian missions provide challenges and rewards for mental
      health nursing not found in the garrison mission. A primary challenge is to
      develop and implement programs that benefit the various populations inherent in
      such missions. During Operation Sea Signal, several programs, such as migrant
      adult day treatment, halfway house, outreach, and inpatient, led to the overall
      enhancement of mental health nursing care for the Cuban and Haitian migrants. It
      also gave the participating mental health nursing team of professionals and
      enlisted technicians the opportunity to develop their nursing expertise and
      sensitivity in a culturally diverse situation.

PMID- 9640029
TI  - Operational stress control in the former Yugoslavia: a joint endeavor.
AB  - The military has developed specialized mental health teams to evaluate and treat
      soldiers diagnosed with stress reactions and neuropsychiatric disorders. The
      response of these mental health teams in support of the year-long peace
      enforcement mission to Bosnia-Herzegovina is reviewed. Demographics and
      operational stressors are examined. Stress control doctrine is tested and
      revised. Credibility with leaders, chaplains, and medical personnel is achieved
      through rapid response to serious injury or fatality. Emphasis is placed on
      successful marketing strategies, stress management and suicide prevention
      classes, prompt access to care, and decreasing the stigma of mental health
      through education. Coordination of mental health assets promotes synergy and
      mission accomplishment.

PMID- 9640030
TI  - Psychological health and trauma in male and female soldiers.
AB  - This study assessed the effect of premilitary and military trauma on the
      psychological health of more than 1,000 female and male active duty soldiers.
      Questionnaire data provided information on demographics, history of trauma
      exposure, and general psychological health as assessed by the Brief Symptom
      Inventory (BSI). The results indicated that females reported experiencing more
      sexual traumas and males reported more nonsexual traumas. BSI subscale scores
      indicated poorer psychological health among all of the subjects compared with BSI
      normative groups and other Army soldiers. The need for military norms for the BSI
      is discussed.

PMID- 9640031
TI  - Early syphilis in an active duty military population and the surrounding civilian
      community, 1985-1993.
AB  - Syphilis among active duty soldiers at Fort Bragg, North Carolina, and the
      nonmilitary population of Cumberland County was examined during a 9-year period
      encompassing the most recent nationwide syphilis epidemic. A total of 762 cases
      of primary and secondary syphilis were recorded between 1985 and 1993, 27% of
      which occurred in soldiers. The epidemic struck both military and civilian
      populations simultaneously; epidemic curves in the two populations were parallel,
      peaking in 1990-1991, with highest annual incidences of 122.6/ 100,000 (military)
      and 48.0/100,000 (civilian). Individual risk factor data were not available for
      analysis, but a relationship was observed between primary and secondary syphilis
      diagnoses in both populations and cocaine arrests in Cumberland County. Our
      findings provide epidemiological support for a high degree of interplay between
      the military and the surrounding civilian communities that has significant
      implications for control of sexually transmitted diseases. Enhanced collaboration
      between military and civilian public health authorities is essential to the
      control of syphilis and other sexually transmitted diseases.

PMID- 9640032
TI  - Senior executive behaviors for the Army Dental Care System of the 21st century.
AB  - Challenges will most likely confront the Army Dental Care System as it moves into
      the next century. Like any other learning organization, the Army dental care
      system must develop a continuous stream of dynamic leaders to direct its
      evolution if it wants to survive. Using the Delphi method, the investigators
      surveyed senior dental leaders to determine the attitudes and behaviors believed
      to be required to perform successfully as commanders, residency directors, and
      senior staff officers. The essential executive behaviors appear to be consistent:
      be honest, act with integrity, be accountable for your actions, be dedicated to
      mission accomplishment, and perform your duty with care and compassion. Relying
      solely on ratings assigned to the behaviors, discriminant function analyses could
      predict proper group membership with an accuracy of 79.4%. When demographic
      information was included, prediction accuracy improved to 96.7%.

PMID- 9640033
TI  - Temporary dental restorative materials for military field use.
AB  - New temporary dental restorative materials are an important military requirement.
      This study compares the critical properties of the currently used temporary
      material, reinforced zinc oxide-eugenol (ZOE), with those of a glass ionomer
      restorative material (GI), a high-viscosity modified glass ionomer material
      (MGI), and two resin-modified glass ionomer materials (RMGIs). Properties tested
      included compressive and tensile strength, rigidity, hardness, bond strength,
      working and setting times, and storage stability. Ranked results for compressive
      strength, rigidity, and hardness were MGI > GI > RMGI > ZOE; for tensile strength
      they were RMGI > MGI > GI > ZOE; and for storage stability they were ZOE > MGI >
      GI > RMGI. Working and setting times were all within reasonable clinical limits,
      and bond strength was heavily dependent on tooth surface preparation. Although
      none of the materials tested met all of the ideal requirements, the high
      viscosity glass ionomer material offers the most promise for military field use.

PMID- 9640034
TI  - Dental sealants: prevalence and need in U.S. military recruits.
AB  - This paper explores the need for and the prevalence of dental sealants in U.S.
      military recruits. The data come from the 1994 Tri-Service Comprehensive Oral
      Health Survey. Data were collected on 2,711 Army, Air Force, Marine Corps, and
      Navy recruits at one recruit in-processing center per service. Women and
      minorities were oversampled. Both bivariate and logistic regression analysis were
      done on the need for at least one dental sealant and the prevalence of at least
      one dental sealant in recruits. Weighted data (101,072) were used for the
      bivariate analyses; unweighted data were used in the regressions. Results show
      that 8.7% of recruits need dental sealants and that 14.8% have dental sealants.
      Need for dental sealants varies across branch of service only, whereas prevalence
      of dental sealants varies across age, race, and branch of service. The cost
      effectiveness of dental sealants in this population should be established.

PMID- 9640035
TI  - Ventilator-related Acinetobacter outbreak in an intensive care unit.
AB  - An outbreak of 16 cases of ciprofloxacin-resistant Acinetobacter baumannii
      (calcoaceticus subspecies anitratus) infections occurred during a 7-month period
      in a medical intensive care unit. Fifteen of the patients developed pneumonia
      associated with ventilator support. Possible sources considered in the outbreak
      investigation were sinks, ice, personnel, patients on multiple antibiotic
      therapy, reusable ventilator circuits, and hemodialysis. The equipment and
      environment associated with the outbreak were cultured. Patients on ventilators
      were significantly more susceptible to Acinetobacter nosocomial infection
      compared with the rest of the patients in the medical intensive care unit (p <
      0.05). Sputum cultures were only 5% sensitive to ciprofloxacin and gentamicin,
      but they were 100% sensitive to imipenem (p < 0.0001). Uncloaking imipenem was a
      significant contributing factor in controlling this outbreak. Once outbreak
      control measures were instituted, Acinetobacter isolates dropped from 77 (during
      the outbreak year) to 9 (during the subsequent year) and no new pneumonia cases
      occurred.

PMID- 9640036
TI  - Perceptions of current and recent military internal medicine residents on
      operational medicine, managed care, graduate medical education, and continued
      military service.
AB  - Current and recent internal medicine residents were surveyed on their level of
      confidence in practicing operational medicine, satisfaction with graduate medical
      education, the impact of TRICARE, the military managed care plan, on their
      patients and education, and intentions on remaining in uniformed service. Their
      sentiments were recorded on a five-point Likert scale (1 = strongly agree, 3 =
      neutral, 5 = strongly disagree). Two hundred twenty-one of the 294 surveys were
      returned (75.2%). Most physicians felt unprepared to perform duties in a nuclear,
      biological, or chemical warfare environment, or handle administrative aspects of
      operational medicine (mean scores, 3.2-3.7). A majority of respondents felt
      satisfied with the quality of their residency experience (mean score, 1.9).
      Although more than half of those surveyed (53.6%) listed the opportunity to teach
      residents as a top factor influencing their retention decision, most felt
      skeptical that graduate medical education would remain important in the future
      (mean score, 3.6). Most physicians agreed that restriction of TRICARE to patients
      less than 65 years old may degrade the quality of military internal medicine
      residencies (mean score, 1.6). Previous service, Reserve Officer Training Corps
      experience, and graduation from the Uniformed Services University of the Health
      Sciences were factors associated with increased physician intention to remain
      beyond their obligated service. The most common factors inducing physicians to
      leave the military included frequent deployments, relocations, and financial
      compensation. Factors cited most frequently as influencing physicians to stay on
      active duty included high-quality colleagues, opportunities for teaching
      residents, and freedom from malpractice and office management details.

PMID- 9640037
TI  - Longitudinal trends and gender differences in physical fitness and lifestyle
      factors in career U.S. Navy personnel (1983-1994)
AB  - This study examines long-term health and physical readiness trends in the U.S.
      Navy. We mailed lifestyle questionnaires to all participants in baseline studies
      between 1983 and 1989 who were still on active duty in 1994. Commands provided
      body composition and physical readiness test scores for the participants. Two
      longitudinal cohorts were created: an 8-year sample (N = 640) with matched data
      from 1986, 1989, and 1994; and an 11-year sample (N = 1,576), with data from 1983
      and 1994. Analyses of both cohorts revealed significant improvements in
      cardiovascular fitness, muscle strength, exercise, lean body mass, dietary
      habits, and sleep, as well as significant decreases in tobacco and alcohol use
      and job stress. However, hypertension rates, percentage of body fat, and body
      mass index increased over time. Women's scores were significantly better than
      men's on a number of factors. Overall, these findings suggest that the Navy's
      health promotion efforts have had a significant positive effect on the fitness
      and health behaviors of career Navy men and women.

PMID- 9640038
TI  - Psychological aspects of pregnancy in the military: a review.
AB  - OBJECTIVES: In the past 20 years, more women have joined the armed forces than
      ever before. Consequently, the management of pregnant service members has raised
      important medical and administrative issues. Recent studies comparing service
      women with their civilian counterparts have shown a significantly increased rate
      of pregnancy complications. This paper explores the psychosocial milieu in which
      active duty pregnancies occur and attempts to elucidate the psychological
      stressors that may contribute to the increased complication rate. METHODS: The
      literature on pregnancy in the military and the existing regulations governing
      its medical and administrative management are reviewed. Case material is
      presented and analyzed. RESULTS AND CONCLUSIONS: Three types of psychological
      stressors are identified and discussed: lack of social supports, the pressures of
      minority status, and the institutional reactions to gender roles. The author
      proposes mandatory education for military leaders regarding sensitivity to
      women's reproductive issues as well as specialized briefings for women inductees
      on the realities and risks of pregnancy in the military.

PMID- 9640039
TI  - The field hospital at Zagreb: tri-service medical care in a peacekeeping
      operation.
AB  - The objective of this investigation was to provide military medical planners with
      insights into the specific materiel, skills, and information requirements
      demanded by humanitarian missions through review of approximately 16,000 records
      from a tri-service medical patient database used at the field hospital in Zagreb,
      Croatia, during Operation Provide Promise. This review describes (1) the origin,
      rationale, structure, and implementation of the database; (2) the patients who
      used medical services provided by the hospital; (3) the diagnoses encountered in
      outpatient visits, admissions, and surgical operations; and (4) the distribution
      of medical services used by various subgroups of interest.

PMID- 9640040
TI  - Injuries in Croatian Army brigade soldiers inflicted in an offensive action
      during the 1991/1992 war in Croatia.
AB  - The type and number of injuries sustained by soldiers of a Croatian Army brigade
      in an offensive action during the war in Croatia (1991/1992) were analyzed
      according to the mechanism of wounding. About 1,000 soldiers participated in a 6
      hour offensive action in a flat, partially swampy, and wooded area, convenient
      for large-scale use of antipersonnel mines and other explosive devices. There
      were 92 casualties in total: 15 soldiers were killed in action and 77 were
      lightly or severely wounded. The mechanism of wounding included shell fragments
      in 44 soldiers (47.8%), antipersonnel mines and gunshot projectiles in 14
      soldiers each (15.3%), and others (fall, blow, stress, etc.) in 20 soldiers
      (21.7%). Death was recorded in 1 of 13 soldiers (7.1%) with gunshot wounds, 11 of
      44 soldiers (25%) wounded by shell projectiles, and 4 of 14 soldiers (28.5%)
      wounded by antipersonnel mines. All injuries inflicted by shell fragments were
      multiple, whereas the type and severity of injury inflicted by antipersonnel
      mines were directly related to the type of mine. Pressure-activated mines
      generally caused limited injuries to the lower extremities, ranging from
      mutilation to amputation. Injuries inflicted by other antipersonnel mines
      resembled those caused by shell projectiles; however, their severity depends on a
      number of factors.

PMID- 9640041
TI  - Clinical and radiological management of wartime eye and orbit injuries.
AB  - OBJECTIVE: The purpose of this study is to present our experience in treating 191
      patients with eye and orbit injuries that occurred during the war in Croatia and
      Bosnia and Herzegovina. METHODS: The authors retrospectively reviewed the
      clinical and radiological management of wartime eye and orbit injuries in
      patients hospitalized at Clinical Hospital Split. RESULTS: Seventy-nine percent
      of the war eye and orbit injuries were caused by fragments of explosive devices,
      9.9% by high-velocity missiles, and 8.4% by other objects. Most of the patients
      were admitted to the hospital within 24 hours of injury. The total number of
      injured globes was 222; 48.2% of globes had intrabulbar (mostly magnetic) foreign
      bodies, and 13% had extrabulbar intraorbital foreign bodies. Extensive wounds
      (perforation, double perforation, rupture, and evisceration/ enucleation) were
      encountered in 74% of patients, and 26% of patients had slight trauma. There was
      a statistically significant correlation between admission within the first 12
      hours and postoperative visual acuity (Chi 2 = 3.93; p = 0.0474). CONCLUSION:
      Along with clinical examination, computed tomography is the most important
      diagnostic procedure in preoperative evaluation of various forms of globe and
      orbit injuries. The admission time is the most important factor in determining
      postoperative visual acuity.

PMID- 9640042
TI  - The Army psychological autopsy: then and now.
AB  - The conduct and reporting of an Army psychological autopsy is a complex and
      relatively infrequent event. The details of these reports may not be completely
      clear to the behavioral sciences personnel tasked with collecting the data. This
      paper reviews the current status of the Army psychological autopsy and contrasts
      it with the development of civilian psychological autopsies. The current thinking
      of the Department of Defense Health Affairs working group on psychological
      autopsies is presented. The epidemiological content of the Army psychological
      autopsy as a scientific resource is presented in the form of an analysis of the
      psychological autopsies for the 1995 Army suicide data. Suggestions for updating
      this unique command tool are included.

PMID- 9640044
TI  - Shoulder arthroplasty in war wounds.

PMID- 9640043
TI  - Hepatitis A and cytomegalovirus infection precipitating acute hemolysis in
      glucose-6-phosphate dehydrogenase deficiency.
AB  - A 34-year-old man presented with acute hemolytic anemia secondary to acute viral
      hepatitis A and a coexisting acute cytomegalovirus infection. This association
      has not been described previously in patients with glucose-6-phosphate
      dehydrogenase deficiency and is the subject of this report.

PMID- 9640045
TI  - [The study of the influence of aminoglycoside antibiotics on the hearing organs
      in children].
AB  - The paper presents results of audiologic assessments hearing examinations in 19
      children that received aminoglycosides in cases of pneumonias, meningitis and
      sepsis. Examination of hearing acuity with otoscopic assessment of the ears,
      tympanometry, ABR and acoustic otoemission were performed before, directly after
      infusion and after completion of treatment. After a laryngological examination
      and of the hearing acuity, tympanometry and the ABR the authors have concluded
      the normal state of the hearing organ. Only in the examination of the acoustic
      otoemission produced during the treatment it was found the amplitude was
      flattened or there was no otoeimssion for some individual frequencies in relation
      to records taken before the treatment. The authors emphasize that among risk
      factors of ototoxic effect of some medicines are of importance the following:
      patient's age, uncontrolled increase in blood drug concentration, increase in
      daily dosage, cumulation of the drug in the organism, prolonged treatment with
      the drug.

PMID- 9640046
TI  - [Dysphagia due to diffuse degenerative changes in the cervical spine].
AB  - Degenerative changes in the cervical spine can produce osteophytes of the
      anterior margins of the cervical vertebrae. Although cervical osteophytes have
      been reported to cause many complications, most remain clinically silent. Very
      few cases of pharyngeal dysphagia and pseudotumoral bulging of pharyngeal wall
      resulting from cervical osteophytes have been described. Dysphagia in these cases
      is caused either by mechanical obstruction or by paraoesophageal inflammation due
      to irritation at the osteophytes processes. We present a case of 63 year-old
      patient suffering dysphagia secondary to cervical osteophytes. ENT examination
      reveal bulged wall of the hypopharynx resemble the tumor. The diagnosis was
      established by conventional X-ray of the spine and CT. We investigated this case
      fully to rule out an alternative pathology.

PMID- 9640047
TI  - [Results of surgical treatment of laryngeal cancer in elderly patients in 1946
      95].
AB  - In the years 1946-1995 in Karol Marcinkowski University School of Medical
      Sciences, Department of Otolaryngology, Head and Neck Surgery the long term
      results on 2223 patients with laryngeal cancer treated surgically according to
      the age were evaluated. Five year survival rates after total laryngectomy in
      elderly persons was 44.2%. Five year survival rates (67.7%) after partial
      laryngectomy justify their application in suitably chosen cases of cancer of the
      larynx.

PMID- 9640048
TI  - [The role of potential duplication of time for the neoplastic cells in patients
      with head and neck cancer treated by radiation].
AB  - Proliferation potential of tumour cells is one of the most important features of
      malignant neoplasms. This factor can be assessed by measurement of the potential
      doubling time (Tpot). This method includes the single intravenous injection of
      thymidine analogue (iodo- or bromodeoxyuridine) with subsequent single biopsy of
      the tumour and simple calculation using flow cytometry data of the specimen. The
      preliminary results of clinical trials show that Tpot determined prior to
      treatment can serve as an independent prognostic factor in patients with head and
      neck cancer receiving conventional radiotherapy. This assay may also help to
      selected a subgroup of patients with high proliferation capacity for whom
      application of accelerated radiotherapy regimens may be advantageous. The aim of
      this paper is to describe the methodology of Tpot measurement and to review the
      clinical radiotherapy trials involving Tpot measurement.

PMID- 9640049
TI  - [Selected parameters of immunologic reactivity in patients with sensorineural
      hearing loss. I. Receptor activity of T lymphocytes].
AB  - Receptors activity of peripheral T cells for sheep erythrocytes was analyzed in
      67 healthy individuals and in the 29 patients with progressive, bilateral hearing
      loss and in 7 patients with sudden deafness on unknown etiology. The ability of T
      lymphocytes to form non-immune complete and incomplete rosettes in TEt and TEa
      tests was evaluated before and at the beginning of ubiquitine therapy. The mean
      values of rosette forming cells (RFC) in percentage and absolute numbers and the
      statistical analysis were presented. It was found that the receptor activity of T
      lymphocytes in TEt test was not significant different from the results of healthy
      control group. On the other hand highly significant differences were observed (p
      < 0.001) in subset of "active" T-cells determined in TEa rosette test. The
      relative coefficient of receptor activity of lymphocytes (CRAL) calculated for
      complete TEa rosettes was high different (p < 0.0008). Normalization of the
      results of TE rosette tests after first period of ubiquitin biotherapy was
      observed.

PMID- 9640050
TI  - [The errors of the operative technique as a cause of unsuccessful tympanoplasty.
      Part II].
AB  - This study is based on the author's personal experience in a middle ear
      reconstructions. Errors can occur at each surgical stage--tympanic membrane and
      chain reconstructions, mobilisation of the footplate. At any moment the surgeon
      can gain or loose the dB. The operating technique is the main factor. A proper
      operative technic includes a good operating approach and excellent hemostasis.
      The tympanic membrane, should be as thin as possible, exactly and carefully
      dissected. Care should be taken to avoid any damage to the fascia graft fibers.
      Bad or unsure material should be discarded. The graft should not be too large
      because if it overlaps the EAC wall, it narrows the canal. If the graft is too
      small, secondary edge performation can occur. The shallow placement of the graft
      risk a bad contact. Opposite--too deep--poor ventilation of the middle ear and
      may lead to adhesions. The annulus should be well prepared, free of epithelial
      remnants. If not cholesteatoma could develop and discontinuity between the
      neotympanium and the ossicular chain abolish the transmission effect. The
      mechanical and lever principles during reconstruction of the sound transmission
      should be kept in mind at all times. The reconstructed system must be delicate
      and light. The round window reflex is the most important indice of good performed
      reconstruction, and should be used similar to the modern monitoring system. Try
      to prevent the natural structures. They are the most valuable material for the
      future reconstruction.

PMID- 9640051
TI  - [Laryngocele].
AB  - Author present four cases of mixed laryngocoele. Planocellular carcinoma of
      larynx was recognized at one of the four patients after 17 months from the
      operation of laryngocoele. A rare case of bilateral laryngocoele described by the
      authors was found in a woman, who was operated on in 1981 because of the internal
      laryngocoele at the left side. She was reoperated in 1995 a mixed laryngocoele at
      the right side was removed.

PMID- 9640052
TI  - [Lobular capillary hemangioma of the nasal septum].
AB  - A case of 27 years old woman cured surgically of lobular capillary hemangioma of
      the nasal septum, which occurred post delivery was described. The current status
      of this subject was presented.

PMID- 9640053
TI  - [Prosper Meniere: unknown and little known facts].
AB  - In the article some less known and unknown facts from Prosper Meniere's life are
      reported. It was emphasized that in foreign bibliography etiology of Meniere's
      disease isn't connected with labyrinthine's hameorrhagia, as it is often stated
      in Polish laryngological literature.

PMID- 9640054
TI  - [Organic nitrates--new perspectives on an old drug group].

PMID- 9640055
TI  - [Current information on the metabolism of flavonoids. I. Absorption and
      metabolism of flavonols].

PMID- 9640056
TI  - [Thalidomide, an unending story].

PMID- 9640057
TI  - [Lipoprotein metabolism disturbances in patients with kidney diseases].
AB  - Lipoprotein(a) was discovered over 30 years age and it is an independent risk
      factor for atherosclerosis, coronary artery disease and peripheral vascular
      diseases. Among patients with end stage renal failure lipoprotein(a) levels are
      higher than in general population and being independent of the type of treatment.
      Cardiovascular diseases are the most important cause of mortality in ESRD
      patients. Moreover we have interesting information about possibility of influence
      of Lp(a) serum levels.

PMID- 9640058
TI  - [The effect of pentoxifylline on treatment results and course of rehabilitation
      of patients after ischemic stroke].
AB  - The study has been taken up to compare the effect of treatment with
      pentoxifylline and typical treatment in early ischaemic stroke. The study
      included 107 patients aged 42-85, with the ischaemic stroke confirmed by CT scan,
      in early stage of stroke (within 24 hours after onset). Excluded from the study
      were patients with severe physical diseases. The patients were divided into two
      groups. Group I was treated typically, group II had been profited from a typical,
      appropriate therapy and pentoxifylline delivery during 30 days as well, with a
      daily dose of 1200 mg i.v. within the first 5 days followed by an oral dose of
      800 mg subsequent days. Such a treatment has been continued until 12th month. The
      neurological state was assessed according to the European Stroke Scale (ESS) and
      Mathew Scale (MS), general fitness according to the Kamofsky Scale (KS) and
      Barthel Index (IB) at the admission, after 30 days and 12 months of the
      treatment. Quality of life assessment using by Oxford Handicap Scale and Frenchay
      Activities Index. After 30 days and 12 months of the treatment, no statistically
      significant differences between all study groups was found in: 1) mortality, 2)
      mean survival time, 3) neurological and functional state, 4) quality of life.
      According to the above results the beneficial influence of pentoxifylline
      treatment of ischaemic stroke was not confirmed.

PMID- 9640059
TI  - [Evaluation of non-cerebral complications in light of ischemic stroke severity].
AB  - Extracerebral complications which were observed in great number of ischemic
      stroke patients increased the risk of death and disability. Pneumonia, myocardial
      infarction, pulmonary embolisms and urinary tract infections are most often. We
      considered the influences of extracerebral complications on anterior circulation
      territory disturbances. A cohort of 1697 patients with first-ever ischemic stroke
      within anterior circulation region was evaluated. Patients were divided into
      three groups: A, B, C according to the heaviness of stroke. We understood the
      heaviness of stroke as a degree of cerebral disfunction occurring within the
      first 24 hours of the onset and assessed it using Clinical Groups of the Whole
      Body Activity (CG WBM). CG WBM is an original classification, a three-degree one,
      prepared by Department of Neurology University School of Medicine Sciences in
      Bydgoszcz. The rate of complications was statistically significantly lower in
      group A with the mild course of ischemic stroke than in group B with moderate or
      in group C with the severe course of ischemic stroke. Pneumonia, myocardial
      infarction and pulmonary embolism were recognized more often in patients with
      fatal outcome. The amount of extracerebral complications raised with the severity
      of the ischemic stroke.

PMID- 9640060
TI  - [Evaluation of the prognostic value of general motor activity for rehabilitation
      of patients after cerebral stroke].
AB  - Following cerebral stroke motor activity of the patient is dependent on the
      extensiveness of brain ischemia. Evaluation of this activity may be an exponent
      of brain ischemia extent. It can be used for the determination of predictability
      of patient survival and results of rehabilitation. Using Mathew and Barthel
      scales effectiveness of treatment and rehabilitation was evaluated four times
      during 12-month follow-up in patients of General Motor Activity Clinical Group II
      i III. The results obtained may be evidence of significant prognostic importance
      of evaluation of general motor activity of the organism in the initial period of
      treatment and rehabilitation only, i.e. within 3 months following cerebral
      stroke. However, it is no importance for evaluation of remote results (one year
      following cerebral stroke). The evaluation of general activity cannot be used to
      predict the dynamics of the improvement of neurological and functional status of
      patients undergoing rehabilitation following cerebral stroke.

PMID- 9640061
TI  - [Concentrations of tumor necrosis factor alpha and interleukin-1 beta in
      cerebrospinal fluid in the course of tick-borne encephalitis].
AB  - CSF concentrations of TNF-alpha and Il-1 beta were detected in patients with TBE.
      The cytokines were detected by immunometric assay by MEDGENIX kit. CSF
      Concentrations of TNF-alpha and IL-1 beta in patients with TBE were significantly
      higher than in control group before as well as after treatment and normalization
      of CSF parameters. These concentrations were lower comparing to one obtained in
      group of bacterial meningitis. There was no correlation between concentration of
      cytokines and other CSF parameters (cytosis, protein, glucose concentration).
      Concentrations of analysed cytokines did not change significantly before and
      after treatment. Detection of CSF concentrations of TNF-alpha and Il-1 beta in
      patients with tick-borne encephalitis can be used to evaluate efficacy of
      treatment and retreat of infection.

PMID- 9640062
TI  - [Allogenic blood stem cell transplants: characteristics of transplantation
      material and clinical transplantation course].
AB  - We have analysed the clinical course of the 14 consecutive allogeneic peripheral
      blood stem cell transplantations (PBSCT) and cellular composition of the grafts.
      Donors were HLA-identical siblings except for the one donor who was only HLA
      phenotypically identical brother. Nine of them were sex-mismatched to their
      recipient. Donors received filgrastim (G-CSF) at a dose of 10 microkilograms/kg
      for 5 days (4-6). Leukaphereses were started at 5 day to obtain the target dose 4
      x 10(6) CD34+ cells/kg recipient weight. Median 24 l of blood (24-36) was
      processed collecting: 10.3 x 10(8)/kg (6.69-18.8) WBC, 9.9 x 10(8)/kg (5.87
      16.02) MNC, 9.72 x 10(6)/kg (0.74-18.98) CD34+ cells, 242.5 x 10(6)/kg (77.9-422)
      T lymphocytes (CD4+ to CD8+ ratio was 1.5), 76 x 10(6)/kg (24-113) B lymphocytes,
      33 x 10(6)/kg (14-88) NK cells and 168.8 x 104/kg (23.1-271.4) CFU-GM with 131.7
      x 10(4)/kg (8.4-297.6) BFU-E. Engraftment times to a neutrophil count (ANC) > 0.5
      x 10(9)/l was achieved at a median of 15 days (range 10-23) in all patients
      whereas the platelet count > 20 x 10(9)/l at a median of 14 days (9-19) in all
      but one patient who received the smallest dose of CD34+ cells. Acute graft versus
      host disease (GvHD) developed in 8 patients who survived more than 30 days. Most
      of them (75%) were patients with chronic myeloid leukaemia (CML). In 4 of them
      GvHD was steroid resistant. Chronic GvHD developed in 3 of 6 evaluable patients.
      We confirm that allogeneic PBSCT result in rapid and longterm trilineage
      engraftment. However, the observation of the increasing incidence and severity of
      acute GvHD in patients with CML will require verification in the larger setting
      of patients after completion of ongoing clinical trials.

PMID- 9640063
TI  - [The role of chemotherapy in treatment of nephroblastoma in children. Report of
      the Polish Pediatric Group re. treatments of solid tumors].
AB  - Retrospective analysis of chemotherapy results of children with nephroblastoma
      was performed in 220 patients aged from 1 yr to 14 yrs of live in 12 centers.
      Stage I nephroblastoma was documented in 24.5% but stage II--in 55.3%.
      Histologically 74.6% cases were diagnosed as medium malignant and 12.7%--high
      malignant. Therapy results were similar to observed in other centers.

PMID- 9640064
TI  - [Results of treating patients with highly malignant non-Hodgkin's lymphomas;
      comparison of treatment efficacy with CHOP and CBVPM-AVBP].
AB  - The treatment of highly of 43 patients with highly malignant non-Hodgkin
      lymphomas were analysed and assessed. These patients were treated at the
      Department of Hematology, Pomeranian Medical Academy within 1981-1990. The
      process was advanced in 76% of and localization of the tumour outside lymph nodes
      was also seen in 79%. The results of treatment with CHOP regimen used during the
      first 5 years were compared with CBVPM-AVBP used in 1986-1990. CBVPM-AVBP regimen
      proved more 4 effective (55% of the complete remissions) than CHOP regimen (37.5%
      of the complete remission). Mean duration of the complete remission (survival
      free from the relapse) was 27.5 (1-88) months. Complete remissions were easier to
      achieve in patients with centroblastic lymphoma in higher percentage. These
      patients survived longer than those with other highly malignant lymphomas. The
      authors conclude that further intensification of chemotherapy in case of highly
      malignant non-Hodgkin lymphomas is justified.

PMID- 9640065
TI  - [Evaluation of the usefulness of stereotactic aspiration fine needle biopsy for
      breast neoplasm diagnosis in the preclinical stages].
AB  - Out of 6000 mammographies performed in the years 1991-1992, 61 patients have been
      qualified to stereotactic fine needle biopsies. Finally 50 stereotactic biopsies
      have been performed on 37 patients. In 6 cases (12%) cancer has been recognized.
      Stereotactic biopsy allows to recognize cancer in preclinical stages. In
      comparison with the surgical this method is less stressing for the patients and
      cheaper.

PMID- 9640066
TI  - [Storage of human bone marrow before transplantation at 4 degrees C. The effect
      of cell proliferation potential particularly in hematopoietic cloned cell lines].
AB  - The possibility of storage of human bone marrow CD34+ cells at 4 degrees C for
      bone marrow transplantation purposes was investigated. The cells were placed in
      Iscove medium supplemented with 20% serum (15% bovine calf serum + 5% human AB
      serum) for three weeks at 4 degrees C. During storage time clonogenicity of
      granulocytic-monocytic (CFU-GM) erythropoietic (BFU-E) and megakaryocytic (CFU
      Meg) progenitors were investigated. It turns out that it is possible to keep
      human CD34+ cells at 4 degrees C for at least few days before transplantation. At
      day four of storage the number of CFU-GM and BFU-E cells still exceeded 50% of
      cells present at day 0. We have found however, CFU-Meg progenitors in comparison
      to others are much more sensitive to metabolic storage stress. This enhanced
      sensitivity of megakaryocytic progenitors could explain at least partially the
      well known ++phenomenon of retardation of thrombopoietic recovery in patients
      undergoing bone marrow transplantation.

PMID- 9640067
TI  - [Social problems of porphyria].
AB  - Late consequences of the attacks of acute porphyrias were studied. Among 312
      patients who were investigated the motor disability (neuropathy) was found in 9
      patients, psychoneurological changes in 1 case and drug abuse in 7 subjects. In
      the group of 200 patients in remission (chosen at random) 72 persons (36%)
      received a disability pension. The existence of problems in change of the
      profession when it was necessary for health-reasons was marked. It was find that
      Dolargan (Pethidine) is too often applied to the patients in remission. It was
      made the warning that drug dependence will arise very easy in patients with
      porphyria.

PMID- 9640068
TI  - [Evaluation of sweating function, changes in heart function and postural blood
      pressure in patients with multiple sclerosis].
AB  - The aim of the study was electrophysiologic assessment of sudomotor function and
      some aspects of cardiovascular system function in patients with multiple
      sclerosis and an attempt of referring assessed variables to duration of the
      disease and EDSS score. The study included 24 patients with clinically definite,
      relapsing-remitting multiple sclerosis and 22 healthy, age-matched controls.
      Autonomic functions were evaluated by means of clinical examination, heart rate
      variability tests, measures of blood pressure in supine and standing position and
      skin sympathetic response examination. Clinical symptoms in patients with
      multiple sclerosis were scarce. Electrophysiologic tests showed no abnormalities
      in heart rate variability and blood pressure response to standing in studied
      group. The majority of patients presented with subclinical dysfunction of
      sudomotor system, indicated by an abnormal sympathetic skin response, which did
      not correlate with duration of the disease or EDSS score. Sympathetic skin
      response examination proved to be a sensitive indicator of autonomic disturbances
      in patients with multiple sclerosis.

PMID- 9640069
TI  - [Use of hypoprothrombinemia provocation test for early diagnosis of liver disease
      caused by harmful environmental agents].
AB  - The aim of this work has been to assess the feasibility of using Prothrombin Time
      (PT) Assay before and after administration of Pelentan (Hypoprothrombinemia
      Provocation (HPP) Test) for early detection of subclinical toxic hepatic
      injuries. The proposed modification of PT Assay is based on the observation that
      people with slight hepatic injury receiving small doses of Pelentan
      (diethylcoumarol) display remarkably longer PT than healthy people receiving
      similar doses of the chemical. The test group comprised 37 people occupationally
      exposed to hepatotoxic agents, 85 males permanently abusing alcohol, while 24
      clinically healthy people, not exposed occupationally to the toxic agents served
      as the control. In addition, 26 hepatitis B and/or C virus carriers were also
      examined. The results show that: 1. HPP test enables assessment of hepatic
      function in patients with suspected hepatic injury and in people permanently
      abusing alcohol; 2. low value of serum prothrombin index 24 h and 48 h after the
      administration of Pelentan is indicative of the positive result of the test; 3.
      HPP test provides more information on the functional condition of liver than
      single PT determination by the Quick assay.

PMID- 9640070
TI  - [Evaluation of efficacy and tolerance sumatriptan at a dose of 50 mg in treatment
      of migraine attack].
AB  - Sumatriptan has been used successfully in the acute treatment of migraine since
      1991. Most patients (70-80%) experience pain relief 2-4 hours after receiving 100
      mg sumatriptan orally. During last few years efficacy of lower doses has been
      studied. Many authors proved that 50 mg of sumatriptan may be as effective as 100
      mg. Our study confirmed that 50 mg oral dose of sumatriptan is sufficient in many
      patients. Headache relief was achieved in 58% of treated patients after single
      dose. The second dose of sumatriptan was effective in next 14% of patients.
      Totally headache relief after two doses of sumatriptan was achieved in 72% of
      patients. The sumatriptan 50 mg was well tolerated; only 10% of patients reported
      adverse events, which were minor and transient.

PMID- 9640071
TI  - [Hereditary cerebellar ataxia syndrome].
AB  - Hereditary cerebellar ataxia syndrome has been described in 68 yrs old man with
      progressive symptoms of muscle disturbances of lys. Next other clinical symptoms
      were observed.

PMID- 9640072
TI  - [Treatment problems of eosinophilic granuloma].
AB  - Two clinical cases of eosinophilic granuloma with pulmonary manifestation were
      observed. Therapeutical problems were discussed and corticosteroids and
      cytostatics were recommended.

PMID- 9640073
TI  - [Diagnostic difficulties with skull and brain injury complications in alcoholic
      patients].
AB  - About 20% of patients treated because of craniocerebral injuries are those after
      an alcohol intake. Great number of these patients slightly bodily injured without
      any focal cerebral deficit are stopped by police. The effects of injuries masked
      by the picture of alcohol intoxication are developed during that time. Published
      data and authors of this paper observations show that atypical clinical picture,
      lack of typical, specific disturbances of cerebral function make diagnosing of
      the effect of craniocerebral injuries difficult. To avoid diagnostic errors in
      inebriate patients with head injuries, the degree of cerebral function
      disturbances together with life-threatening risk factors should be carefully
      evaluated. Afterwards the range of diagnostic methods can be established. If the
      wide range of diagnostics is not necessary, patients should be observed over the
      period of a few hours. The authors present original 63-points Scale of Brainstem
      Insufficiency (ITC). This ITC scale assesses: consciousness, the whole body
      movements, vegetative functions (breath temperature, blood pressure, pulse),
      pupils and eye movements movements. This scale can be used for evaluation of
      global cerebral function disturbances observed in not only craniocerebral
      injuries but in alcohol intoxication as well.

PMID- 9640074
TI  - [The role of nutrition on the treatment of septic syndrome and multiple organ
      failure].
AB  - Basing on current literature the issues regarding nutrition in patients with
      septic syndrome and multiple organ failure were discussed. It was emphasised that
      patient feeding along with providing metabolic substrates also serves as a
      treatment method. Diet ingredients in specific carbohydrate, protein and fat
      metabolism disorders were analysed. We focused upon the role of emulsion of fat,
      especially medium chain triglycerides (MCT) and -3-linolenic acid (fish oil). The
      unique role o f glutamine, arginine and branched chain amino acids (BCA) was
      highlighted. Patient nutrition with accordance to the presented new methods has
      become an efficient routine of treatment in septic syndrome. It may constitute an
      efficient prophylaxis against multiple organ failure.

PMID- 9640075
TI  - [Management of pancreatic injury].

PMID- 9640076
TI  - [Kava-kava preparations--alternative anxiolytics].
AB  - Since Cook's world cruises (1772-1775) there is written evidence of the use of
      kava-kava by the inhabitants of the Pacific Islands. In last decades kava-kava,
      an extract of the plant Piper methysticum was used in several European countries
      (drugs like Laitan, Antares, Viocava, Mosaro etc.). In the presented paper the
      authors describe the pharmacology, toxicology and pharmacokinetics of the active
      compounds of kava-kava the kavapyrones. The discussion concerning the therapeutic
      value of kavapyrones ends with the conclusion of the authors, that kava-kava may
      be a useful alternative for synthetic anxiolytics.

PMID- 9640077
TI  - [Urinary excretion of extracellular matrix proteins in insulin dependent diabetes
      mellitus].
AB  - The purpose of the study was to assess urinary excretion of extracellular matrix
      proteins and proteolytic enzymes in 12 subjects with IDDM with albuminuria, 12
      subjects with IDDM without microalbuminuria and 10 normal healthy subjects.
      Urinary excretion of FN was significantly higher in subjects with IDDM and
      albuminuria as compared to patients with IDDM without microalbuminuria and
      healthy subjects (223.6 +/- 143.2 vs. 103.2 +/- 59.7 vs. 58.3 +/- 12.0 ng/mg
      creatinine, p < 0.01). Urinary level of type IV collagen was significantly
      elevated in subjects with IDDM and albuminuria as compared to IDDM without
      microalbuminuria and healthy subjects of cathepsin B was significantly higher in
      diabetic patients with albuminuria as compared to patients without
      microalbuminuria and healthy subjects (0.82 +/- 0.53 vs. 0.25 +/- 0.17 vs. 0.22
      +/- 0.05 mlU/mg creatinine, p < 0.01). Urinary activity of plasmin was
      significantly elevated in diabetic patients with albuminuria as compared to
      subjects without microalbuminuria and healthy control (0.477 +/- 0.37 vs. 0.194
      +/- 0.09 vs. 0.21 +/- 0.02 mlU/mg creatinine, p < 0.01). Our data indicate that
      increase in the urinary excretion of extracellular matrix proteins may be the
      useful tool for monitoring glomerular injury.

PMID- 9640078
TI  - [Mutation T-->C of nucleotide 2238 in the gene of atrial natriuretic peptide
      (ANP) precursor and heterogeneity of sodium-sensitive hypertension. Preliminary
      report].
AB  - Atrial natriuretic peptide (ANP) is involved in the pathogenesis of sodium
      sensitive hypertension. The loss of Sca I restriction site in the ANP precursor
      gene abolishes the regular stop codon. The aim of our study was the analysis of
      the Sca I gene polymorphism in 23 patients with sodium-sensitive hypertension,
      the molecular characteristic of the mutation and the comparison of the blood
      pressure values, plasma renin activity, plasma ANP and aldosterone concentration
      between patients with or without mutation. Applying the polymerase chain reaction
      (PCR), followed by digestion with Sca I, the heterozygous mutation has been found
      in 9 (39%) patients. The sequencing of PCR products indicated that the loss of
      Sca I restriction site is caused by T2238-->C transition leading to the
      translation of ANP with two additional arginines. The higher concentration of ANP
      in plasma has been found in T2238-->C transition patients on normal and high
      sodium diet as compared with patients without mutation. These preliminary results
      suggest that the heterogeneity of sodium-sensitive hypertension is associated
      with the T2238-->C mutation of the ANP precursor gene.

PMID- 9640079
TI  - [Evaluation of platelet function and tissue plasminogen activator activity in
      ischemic heart disease depending on concurrence with hyperlipoproteinemia and
      aspirin therapy].
AB  - Platelet activation, impairment of fibrinolysis and dyslipidemia are important
      factors in the pathogenesis and progression of ischemic heart disease. Aspirin
      therapy will reduce platelet activation both by its negative effect on platelet
      aggregation (SPA) and by inhibition of granule release which liberates such
      mediators as platelet factor 4 (PF4) and plasminogen activator inhibitor 1 (PAI
      1). The present study was performed in 57 patients with ischemic heart disease
      (IHD), divided into groups depending on coexistent hyperlipoproteinemia (HLP) and
      aspirin treatment. The control group included 21 healthy individuals, matched for
      age and sex. Parameters of hemostasis (SPA, PF4, PAI-1) and concentration of
      lipid fractions (TC, TG, LDL, HDL) were measured in plasma. Increased PF4 levels
      were found in all groups with IHD, irrespective of hyperlipoproteinemia or
      aspirin treatment. Enhanced SPA and higher PAI-1 were limited to group IHD-HLP
      without aspirin. Highest PAI-1 activities were observed after stimulation of
      platelets in vitro. In conclusion, patients with IHD and hyperlipoproteinemia
      presented most pronounced platelet activation and impairment of fibrinolysis.
      Aspirin had a beneficial effect on these changes. Lower activities of PAI-1, in
      patients treated with aspirin, can be ascribed to its reduced release from
      platelets. Aspirin did not satisfactorily reduce the level of PF4, although it
      strongly inhibited SPA.

PMID- 9640080
TI  - [Zinc protoporphyrin (ZPP) in diagnosis of anemia].
AB  - In iron deficiency, zinc protoporphyrin (ZPP) is produced instead of heme, and
      the ZPP concentration in erythrocytes increased (normal value < 2.3 micrograms
      ZPP/g Hb). The ZPP level and comparison with the other normally used tests in
      iron deficiency in the group of the patients with iron deficiency, ACD, MDS, AML,
      plasmocytoma was investigated. The ZPP level was determined by hematofluorometry
      in samples from 96 patients. Thirty five patients with iron depletion showed
      decreased both serum ferritin (median 5.9 ng/ml), and hemoglobin level (median
      9.8 g/dl) with significantly increased ZPP level (median 8.5 micrograms/gHb). An
      increased level of ZPP (median 3.95 micrograms/gHb) with normal level of ferritin
      (median 24 ng/ml) and iron (median 50 (g/dl) in the serum of patients with ACD
      was determined. Measurement of ZPP level in the combination with ferritin and
      peripheral blood morphology allows to classify the degree of iron deficiency. The
      ZPP levels higher than 4.55 micrograms/gHb confirms iron deficiency in the group
      of anaemic patients.

PMID- 9640081
TI  - [The influence of salmon calcitonin on the soluble form of VCAM-1 (CD 106) and E
      selectin (CD 62E) in serum of patients with atopic bronchial asthma].
AB  - The aim of the study was to evaluate the effect of salmon calcitonin (CT) on
      serum level of soluble form of VCAM-1 (sVCAM-1 = soluble vascular cell adhesion
      molecule-1) and E-selectin (sE-selectin = soluble E-selectin) in patients with
      atopic bronchial asthma. Twenty-four individuals divided into 4 groups (6 persons
      each) were investigated. The first group consisted of patients with chronic
      moderate bronchial asthma, the second and third groups consisted of patients with
      mild bronchial asthma and the fourth group K consisted of healthy individuals.
      The patients of the first and second group were treated with CT at a dose of 100
      i.v./days s.c. for three days. The patients of the third group were given placebo
      (phychological saline) in similar way as CT. The indices were measured before the
      treatment with CT or placebo and on the 4th day of the treatment. It was found
      that CT treatment decreased sVCAM-1 in serum only in the patients of the first
      group (p < 0.05) but had no effect upon sE-selectin level. The obtained results
      suggest that CT interfered into mechanisms of inflammation involving adhesion
      molecules in patients with bronchial asthma.

PMID- 9640082
TI  - [Renal proximal disfunction based on activity of n-acetyl-beta-d-glucosaminidase
      in urine of patients with kidney failure].
AB  - N-acetyl-beta-D-glucosaminidase (NAG) urine activities of 63 patients with stable
      and unstable chronic renal failure have been investigated. The values of NAG
      activity obtained from these patients were compared with NAG activity of 33
      normal controls. Abnormal NAG values (> 70 nmol/mg of creatinine) were found in
      60 (95.2%) patients with chronic renal failure and the median of all values was
      327.8 nmol/mg of creatinine. It was 14-fold greater than the median of values for
      normal controls. There were any significant differences of NAG values between the
      patients with massive proteinuria (> 1.5 g/24 h), moderate proteinuria and those
      without 24 hour proteinuria or non-significant proteinuria (respectively 423.5 +/
      286.3 vs 414.4 +/- 334.8 vs 453.0 +/- 451.3 nmol/mg of creatinine). There was no
      significant difference between the two subgroups of patients with NAG values
      above and below 280 nmol/mg of creatinine in age, gender, serum urea and uric
      acid levels. However, the incidence of patients with NAG values higher than 280
      nmol/mg of creatinine was statistically significant in unstable course of renal
      insufficiency and raised serum creatinine levels. It is suggested that the
      measurement of NAG excretion may be helpful to monitor unstable process in renal
      failure.

PMID- 9640083
TI  - [Liver failure in the course of Wilson's disease--report of two cases].
AB  - Wilson's disease is an autosomal recessive disorder characterized by inability to
      excrete copper, and manifests by hepatic, neurologic or/and psychiatric symptoms.
      The therapy is available if diagnosis is made in time. The hepatic form of the
      disease is rarely recognized in Poland. The authors describe two patients with
      Wilson's disease who developed acute hepatic failure leading to death, in the
      first case within few months, in the second within few weeks. The diagnosis was
      established in the terminal stage of the disease and attempts of treatment were
      uneffective.

PMID- 9640084
TI  - [Fibromuscular dysplasia of the internal carotid artery as a cause of transient
      cerebral ischemia episodes].
AB  - A case of fibromuscular dysplasia affecting internal carotid artery is described.
      It is presented clinically as repeated episodes of transient monocular blindness
      on the affected side. We discuss clinical, pathological, color doppler and
      angiographic findings characteristic for this type of pathology.

PMID- 9640085
TI  - [Noninvasive diagnosis of extracranial and peripheral artery diseases].

PMID- 9640086
TI  - [The influence of physiopathologic and genetic factors on drug
      biotransformation].

PMID- 9640087
TI  - [Uremic pruritus--pathogenesis and treatment].

PMID- 9640088
TI  - [Beta-adrenolytic drugs in heart failure--hopes and reality].

PMID- 9640089
TI  - [Endoral donor bone removal for autografts. A comparative clinical study of donor
      sites in the chin area and the retromolar region].

PMID- 9640090
TI  - [Universal building cable installation in the dental practice].

PMID- 9640091
TI  - Predicting extreme patterns of long-term course of psychogenic impairment: a ten
      year follow-up.
AB  - This longitudinal study identifies predictors of course and etiologically
      relevant factors of psychogenic disorders. Since 1979, the Mannheim Cohort
      Project on the Epidemiology of Psychogenic Disorders has investigated neurotic
      spectrum disorders, personality disorders, stress reactions, and somatoform
      disorders in the normal population. Using these data, a cohort of probands
      suffering from moderate psychogenic impairment (N = 240; 121 men, 119 women)
      based on a representative sample of the urban adult population (N = 600; with
      cohorts 1935, 1945, 1955; gender distribution 1:1) of Mannheim, an industrial and
      university town in Germany, was followed up for almost 10 years. The cohort was
      investigated three times by psychodynamically trained physicians and
      psychologists. Tests were performed by means of cluster analysis. Different types
      of course of psychogenic impairment were identified. Both extreme types--the
      probands with the most positive and the most negative spontaneous long-term
      course--were investigated with regard to potential course-determining variables.
      Personality variables and conditions of early childhood development considerably
      influenced the spontaneous long-term course.

PMID- 9640092
TI  - Accessibility of government-run sheltered workshops to people with psychiatric
      histories.
AB  - Government-run sheltered workshops in the Netherlands are not as easily
      accessible to people with psychiatric histories as they are to other groups, such
      as those with physical and intellectual disabilities. This was found in a large
      scale nationwide study in 21 such workshops, commissioned by the Dutch Ministry
      of Social Affairs and Employment. The workshops varied in their degree of
      accessibility. The more accessible ones placed stronger emphasis on social
      objectives and had shorter waiting periods and more lenient admission policies.

PMID- 9640093
TI  - Detecting errors in a scoring program: a method of double diagnosis using a
      computer-generated sample.
AB  - This paper discusses a new method for locating errors in diagnostic computer
      scoring programs for structured clinical interviews. It was proposed as a test of
      the accuracy of the scoring program for the Composite International Diagnostic
      Interview, version 1.1. The proposal was to create an independent scoring program
      in a different computer language but serving the same criteria. Both programs
      were then applied to the same large set of valid (i.e., logically consistent)
      computer-generated test cases, and differences in diagnostic assignments
      reviewed. The method described can identify the program steps that account for
      the sources of the errors. Corrections can be made and the programs run again on
      new sets of test cases until discrepancy-free results are achieved. While this
      method cannot discover errors that are repeated in the two programs, it does
      discover more of the errors in a scoring program than we have previously been
      able to identify. This technique provides a systematic and rigorous approach to
      assuring the accuracy of scoring programs based on established algorithms.

PMID- 9640094
TI  - Symptom distress and frequency of life events.
AB  - A study of the frequency of life events was conducted in a group of subjects
      selected from the general population over a period of 9 months. Four assessments
      were made, using an events questionnaire and the Psychiatric Symptom Index (PSI),
      at 3-monthly intervals. The results show a significant relationship (maintained
      over time) between PSI score and the number of upsetting events, but no
      significant relationship between PSI score and non-upsetting events. These
      observations are interpreted as follows: the higher frequency of upsetting life
      events is secondary to the previous psychological pattern of subjects.

PMID- 9640095
TI  - Psychiatric disorder and disability in a rural community.
AB  - This study examined the relationship between psychiatric disorder and disability
      in a rural community and the use of formal and informal services in the
      management of such disabilities. It was found that of the 26% of the surveyed
      population who obtained a positive current psychiatric diagnosis, 48.3% had
      required assistance in managing at least one activity of daily living. The
      majority of those seeking assistance in managing these functional problems did so
      from family and friends rather than from formal agencies. Psychiatric disorder
      was found to lead to disability as frequently as did physical disorder, with
      almost 50% of those who had experienced mental health problems reporting that
      they were currently unable to carry out at least one activity of daily living.
      The finding that assistance was sought primarily from family and friends raises
      important questions about the nature of psychiatric disorder as a public health
      problem.

PMID- 9640096
TI  - Arrest among psychotic inpatients: assessing the relationship to diagnosis,
      gender, number of admissions, and social class.
AB  - The present study of psychotic patients investigates the relationship of specific
      psychotic diagnoses (i.e., psychoactive-substance-induced psychosis,
      schizophrenia, bipolar disorder, other DSM-III Axis I psychotic disorders),
      social class, gender, and number of admissions to the rate of arrest in the
      community. All admissions with psychotic symptoms to hospitals providing
      inpatient psychiatric services in the Baltimore area were surveyed during a 6
      year period. Study participants were assessed using a modified version of the
      Diagnostic Interview Schedule. During the course of the interview, patients were
      asked whether they had ever been arrested as a juvenile or as an adult. After
      adjusting for age, gender, number of admissions, and social class, we found that
      patients admitted for psychoactive-substance-induced psychosis were more likely
      to report having been arrested than patients with other psychotic diagnoses.
      Patients with schizophrenia were not more likely to have an history of arrest
      than patients with other psychotic disorders. Number of admissions and social
      class were independent predictors of history of arrest. The relationship between
      psychotic diagnosis and history of arrest was modified by gender. Psychotic
      patients with substance-induced diagnosis who were male were more likely to
      report a prior arrest in the community than their female counterparts. Our
      results suggest that type of psychotic diagnosis and social class, in addition to
      gender and number of admissions, are important predictors of differences in
      arrest-rate histories among psychotic patients. Gender appears to be an effect
      modifier of the relationship between psychotic diagnosis and history of arrest.

PMID- 9640098
TI  - Factors related to utilization of services for mental health reasons in Montreal,
      Canada.
AB  - This study examines factors related to the utilization of services for mental
      health reasons by Montreal residents. Data were drawn from telephone interviews.
      A random sample of 893 respondents completed a questionnaire on service
      utilization and the Diagnostic Interview Schedule Self Administered to assess DSM
      III-R psychiatric disorders. Results indicate that 12.8% of the population had
      used such services in the past year. Medical doctors and psychiatrists, whose
      services are free of charge under universal health coverage, were consulted,
      respectively, by 4.1% and 2.0% of respondents. Psychologists, whose services are
      not free, were seen by 3.4% of respondents. In all, 42.0% of respondents who
      presented a current diagnosis used services in the past year. The highest
      proportion of users (48.0%) was found among respondents who presented both
      current and lifetime diagnoses and among respondents with comorbidity. The choice
      of caregiver was related also to pattern of disorders: respondents with current
      and comorbid disorders tended to consult general practitioners, while respondents
      with lifetime disorders or with lifetime and current disorders favoured
      specialized care. In line with other studies, self-perception of mental health,
      gender and marital status were related to utilization; unlike other studies,
      attitudes and age were not. It is argued that particularities found in this study
      stem not only from methodological considerations, but also from the configuration
      of the mental health system in Quebec, where the greater availability of
      psychologists may facilitate service utilization.

PMID- 9640097
TI  - Prevalence estimates of cognitive impairment in medical model adult day health
      care programs.
AB  - Despite an increasing emphasis on adult day health care (ADHC) programs as
      alternatives to institutional care for persons with dementia, little research
      based on direct assessment of clients' cognitive status has been conducted in
      such settings. The goal of this analysis was to estimate the prevalence of
      cognitive impairment among ADHC clients using commonly used screening measures.
      Age-adjusted and non-age-adjusted prevalence estimates of cognitive impairment in
      New York State ADHC programs were developed using a probability sample of 336
      clients. Estimates were made using traditional cutting scores on standard
      cognitive screening measures, such as the Mini-Mental State Examination (MMSE),
      as well as latent class analyses applied to the same item sets. Average
      prevalence estimates of cognitive impairment were 55% across age cohorts and 60%
      for persons aged 65 and over. The MMSE yielded a prevalence estimate of 58%
      across age cohorts and 63% for those aged 65 and over. Using a more conservative
      cut score, the estimate for the MMSE was 33%; latent class estimates of moderate
      to severe impairment indicate that approximately 30% of the ADHC clients had
      cognitive impairment suggestive of probable or definite dementia. Community
      alternatives to institutional care for the elderly are increasing in popularity.
      These findings suggest that 1. While institutions are serving the most severely
      cognitively impaired, age-adjusted prevalence ratios for the ADHC sample approach
      the bounds of the institutional estimates. 2. The institutional setting will
      continue to be an important mode of care for the more severely impaired
      individuals. 3. Daycare is serving a high proportion of the mildly and moderately
      cognitively impaired individuals. It follows, therefore, that such programs need
      to address the needs of these individuals by developing specialized care plans
      and tracks targeted for the cognitively impaired.

PMID- 9640099
TI  - Experimental infection with Ehrlichia phagocytophila in cattle.
AB  - Twenty Norwegian Red cattle, aged 8-10 months were used. Ten animals were
      inoculated intravenously with 3 ml of a whole blood dimethyl sulphoxide stabilate
      of a bovine strain of Ehrlichia (Cytoecetes) phagocytophila. The animals were
      observed on a daily basis for clinical symptoms and rectal temperatures were
      recorded daily for 36 days post inoculation. Blood and serum samples were
      collected regularly during the observation period. All infected animals developed
      fever of 2-4 days duration within a week. Six out of 10 animals had secondary
      temperature rises of 1-2 days duration. Three animals showed swellings in the
      hind limbs and a stiff gait. Compared with the control group, there was a 10%
      decrease in the mean haematocrit and a leukopenia that initially was due to a
      lymphopenia and later to a neutropenia. A monocytosis occurred after the
      subsidence of the primary fever period. A thrombocytopenia occurred during the
      early phase of infection. Granulocytic inclusions were detected for 18-32 days.
      All infected animals developed antibodies > or = 1:4096 to E. phagocytophila
      within 14 days post infection.

PMID- 9640100
TI  - Epidemiological aspects of dermatophyte infections in horses and cattle.
AB  - Ringworm infections in the principal domestic animals are a major public and
      veterinary health problem. The aetiology, epidemiology and symptomatology of
      these mycoses are quite heterogeneous and complex. In this context, the AA
      carried out an epidemiological study to investigate the prevalence of
      dermatophytes in two different animal species, horses (n = 200) belonging to 10
      private stables and cattle (n = 1900) belonging to farms with different breeding
      purposes and management. With regard to horses the results showed a positive
      level of 9% and Trichophyton equinum was the major organism isolated. The results
      concerning the cattle showed positive values that varied both in relation to the
      type of animals and their management as well as to the productive objectives: 19%
      in intensive beef breeding, 4.5% in intensive dairy farms (the aetiologic agent
      isolated in both types of farms was Trichophyton verrucosum) and 8% in
      traditional-type farms (the species of fungi isolated were T. verrucosum and
      Trichophyton mentagrophytes). The results are discussed both in clinical and in
      hygiene and management terms.

PMID- 9640101
TI  - Serological studies on Corynebacterium pseudotuberculosis infections in goats
      using enzyme-linked immunosorbent assay.
AB  - Corynebacterium pseudotuberculosis was isolated from a goat suffering from
      caseous lymphadenitis and used for preparation of cell wall antigens and exotoxin
      for detection of specific antibodies in enzyme-linked immunosorbent assay
      (ELISA). In immunoblotting sodium dodecyt sulphate (SDS) extracted cell wall
      antigens revealed molecular weights ranging from 20 to 120 kDa. The raw exotoxin
      showed molecular weights of 30 and 55 kDa and an inhibition of the haemolysis of
      a Staphylococcus aureus strain. For validation of the ELISA 109 goats of known
      clinical status were examined reaching a sensitivity of 96% and a specificity of
      76% for this test. No serological reactions showed in 191 goats originating from
      11 flocks which never had suffered from caseous lymphadenitis. Using this ELISA
      test 24 goats originating from flocks suffering from caseous lymphadenitis were
      examined serologically before and after vaccination with a bacterin. Before
      vaccination one of the five goats with clinical signs showed no positive reaction
      in ELISA. After vaccination all 24 animals showed positive reactions. Of a total
      of 1868 goats sampled in Baden-Wuerttemberg 41 (2.2%) in 22 (10%) flocks showed
      positive reactions in ELISA.

PMID- 9640102
TI  - Assaying granulocyte phagocytosis by chemiluminescence: effect of storage time
      and temperature of blood samples.
AB  - The objective was to study the effect of storage of blood samples for up to 4.5 h
      at either room temperature or on ice on granulocyte phagocytosis as assessed by
      chemiluminscence. The study included three groups of animals: eight pigs, seven
      cows and eight horses, which were bled at one occasion. The blood samples were
      divided into two and stored either at room temperature or on ice. Granulocyte
      phagocytosis in the samples was then assessed every 60 min starting 30 min and
      finishing 4.5 h after bleeding. The phagocytosis was recorded as the AUC of
      chemiluminescence following phagocytosis of opsonized zymosan particles. The time
      of storage of blood samples had a significant (P < 0.001) overall effect on the
      chemiluminscence following phagocytosis in all species tested, as was the case
      with storage temperature (P < 0.001). It should be noted, however, that there
      were considerable species differences in the effect of the storage on the
      granulocyte phagocytosis. Hence, for valid comparisons of data on granulocyte
      phagocytosis assessed by chemiluminiscence it is important that the handling
      procedures of the blood samples have been applied consistently even if the assays
      have been performed only a few hours after blood collection.

PMID- 9640103
TI  - [Migration and transposition of Oesophagostomum quadrispinulatum larvae from
      feces].
AB  - Investigations on the migration and translation of free-living stages of
      Oesophagostomum quadrispinulatum, using faeces containing eggs as starting
      material, revealed that mostly third stage larvae and very few second stage
      larvae migrated out of faeces, whereas first stage larvae remained in the faeces.
      The emigration rates depended on ambient relative humidity. Compared with the
      control, third stage larvae emigrated out of faeces at rates of 0.3%, 1.6% and
      12.2% at 50%, 75% and 100% relative humidity, respectively. Offering helminth
      free faeces, emigrated third stage larvae returned into faces at rates of 0.4
      1.2%, 5.8-17.7%, 39.0-52.7%, and 45.2-60.7% after 1 h, 24 h, 5 days and 14 days,
      respectively. After a period of 1, 2, 3 or 4 weeks staying out of faeces,
      emigrated third stage larvae returned into faeces at rates of 23.3%, 8.8%, 22.1%
      and 6.0%, respectively. An examination of the horizontal translation revealed
      that most of the third stage larvae migrated distances up to 80 cm and a few even
      up to 150 cm returning into helminth-free faeces.

PMID- 9640104
TI  - Studies on biochemical, serological and further characteristics of Streptococcus
      porcinus.
AB  - In the present study 70 Streptococcus porcinus isolates could be identified and
      further characterized by cultural and biochemical properties, by determination of
      their antibiotic susceptibility and by serological classifications. The S.
      porcinus included serogroup- and serotype-reference strains, presumptive group
      candidates and isolates obtained from routine diagnostics. All cultures
      investigated appeared with a broad zone of beta-haemolysis on sheep blood agar
      showed a CAMP-like reactivity in the zone of staphylococcal beta-lysin and had
      the typical biochemical properties of this species. Determination of antibiotic
      susceptibility revealed a high number of cultures to be susceptible to
      ampicillin, bacitracin, chloramphenicol, penicillin and vancomycin. Resistances
      could be observed for erythromycin, minocycline, sulfamethoxazole-trimethoprim,
      streptomycin and tetracycline. Serogrouping and serotyping could be performed
      with autoclaved extracts of the bacteria and group- and type-specific antisera
      prepared against reference strains and group candidates by immunodiffusion
      reactions. By serogrouping almost all cultures could be classified into serogroup
      E, U, V or P. Some group E streptococci could additionally be serotyped with type
      II, VI, VII and group X specific antiserum indicating that group X represents an
      additional type antigen of serogroup E. None of the antigen preparations reacted
      with serotype IV, V or group candidate NG1 specific antiserum. The described
      properties might help to identify and further characterize isolates of the
      species. S. porcinus, possibly useful in epidemiological aspects.

PMID- 9640105
TI  - Comparative studies of diagnostic bacteriological methods for the recovery of
      Salmonella from faecal samples from flocks of layers.
AB  - Several conventional culture procedures were compared for the recovery of
      Salmonella from faecal samples of layer flocks. The cultural media employed
      consisted of Rappaport-Vassiliadis and tetrathionate broth for selective
      enrichment and three different plating media (Brilliant Green, Xylose-Lysine
      Desoxycholate and modified semisolid Rappaport-Vassiliadis medium). The initial
      enrichment and plating procedures were repeated in a four-stage secondary
      enrichment. Selective enrichment in Rappaport-Vassiliadis or tetrathionate broth
      followed by plating on modified semisolid Rappaport-Vassiliadis medium (selective
      motility enrichment) resulted in a significantly higher isolation rate for
      Salmonella from faecal samples of layers compared to Brilliant Green and Xylose
      Lysine-Desoxycholate medium. The selective enrichment yielded additional
      Salmonella isolates up to the second stage. Further enrichment did not increase
      the isolation rate.

PMID- 9640106
TI  - Report of a case of pyogenic arthritis associated with Actinomyces pyogenes in a
      chamois (Rupicapra pyrenaica).
AB  - A case of pyogenic arthritis associated to an Actinomyces pyogenes infection in a
      chamois (Rupicapra pyrenaica) is described. The animal was a 5-year-old female
      that had been seen alone in a wooded area close to a small town in November 1995,
      and was lame on one front limb. One month later, it was seen again in a nearby
      area. Its lameness had worsened and it knuckled on both front limbs while eating.
      Its nutrition status had worsened considerably. On 8 January 1996 the animal was
      found dead. It was cachectic, its metatarsal/metacarpal-digital joints were all
      swollen and its hoofs were longer than normal. The microbiological study of the
      samples obtained showed a large number of beta-haemolytic colonies subsequently
      identified as Actinomyces pyogenes. Obligate anaerobic bacteria were not isolated
      from the samples.

PMID- 9640107
TI  - Raman spectroscopy.

PMID- 9640108
TI  - Intravenous anaesthesia: a step forward.

PMID- 9640109
TI  - Pharmacokinetic concepts for TCI anaesthesia.
AB  - The development of new short-acting anaesthetic drugs, improved drug assay
      techniques and the availability of reliable infusion systems opened the field of
      clinical pharmacokinetics and pharmacodynamics. The tri-exponential drug
      concentration decay complicates the definition of therapeutic dosage regiments
      and prevents straightforward prediction of recovery from drug effects. The
      context-sensitive half-time, the time required for drug blood concentration to
      decrease to half its value, provides a useful comparative predictor of drug
      concentration decline after infusion. The effect-site equilibration time
      contributes to the delay of drug effect and intensifies the disequilibrium
      between drug blood concentrations and obtained effect following incremental
      dosage. The rationale for drug infusion is reduction of fluctuating drug
      concentrations and drug effects. A variability similar to that observed with the
      use of inhalation agents, must be achieved by the choice of an appropriate
      pharmacokinetic model. The use of a target controlled infusion device, delivering
      proportional changes based on pharmacokinetic principles, allows titration of the
      concentration against clinical effect in individual patients.

PMID- 9640110
TI  - The development of 'Diprifusor': a TCI system for propofol.
AB  - The 'Diprifusor' target controlled infusion system has been developed as a
      standardised infusion system for the administration of propofol by target
      controlled infusion. A preferred set of pharmacokinetic parameters for propofol
      was selected using computer simulation of a known infusion scheme with
      pharmacokinetic parameters described in published literature. The selected model
      was included in a 'Diprifusor' module that was interfaced with, and later
      incorporated into, a computer-compatible infusion pump. Clinical trials with such
      systems led to guidance on appropriate target concentrations for the
      administration of propofol by 'Diprifusor' target controlled infusion for
      inclusion in drug prescribing information. Standardisation of the delivery
      performance (+/- 5%) of commercial systems has been achieved with a laboratory
      performance specification. Clinical studies indicate that the actual blood
      concentrations achieved were about 16% greater than the calculated values
      displayed by the system. In an individual patient, titration of the target
      concentration is required in the same manner as an anaesthetic vapouriser is
      adjusted to obtain a specific pharmacodynamic effect.

PMID- 9640111
TI  - Development of the technology for 'Diprifusor' TCI systems.
AB  - The availability of fast-acting intravenous drugs for anaesthesia has encouraged
      anaesthetists to gain a practical understanding of the pharmacodynamics and
      pharmacokinetics of these drugs to optimise their administration. 'Diprifusor'
      technology uses pharmacokinetic modelling to control the infusion rate of a pump,
      providing the anaesthetist with direct control of the blood concentration rather
      than indirect control by the infusion rate. The 'Diprifusor' electronics module
      is a dual microprocessor component that can be incorporated into an infusion pump
      to provide this mode of administration. This paper describes the module's
      infusion control system, prefilled syringe recognition system and the safety
      aspects addressed by the design.

PMID- 9640112
TI  - Practical use of 'Diprifusor' systems.
AB  - This paper describes practical aspects relating to the safe use of target
      controlled infusion systems in anaesthesia. Consideration is given to the correct
      use of syringes and infusion lines for any target controlled infusion system. The
      importance of appropriate connections, minimising infusion line dead space and
      the avoidance of syphoning are emphasised. The first two commercially available
      infusion pumps to incorporate the 'Diprifusor' module for the administration of
      propofol by target controlled infusion are the Graseby 3500 (Graseby Medical Ltd)
      and the Vial Master TCI (Fresenius Vial SA, originally developed by Becton
      Dickinson). Particular features of these systems are discussed. Finally, the
      practical consequences of possible misuse of infusion systems incorporating
      pharmacokinetic models are considered.

PMID- 9640113
TI  - TCI: supplementation and drug interactions.
AB  - The pharmacokinetic and pharmacodynamic interactions between propofol and
      adjuvant agents have increasingly been recognised as clinically important and the
      improved knowledge of these interactions is being used to optimise the quality of
      intravenous anaesthesia. It is now known that propofol interferes with opioid
      metabolism, thereby increasing the plasma concentrations of the opioids, while
      opioids such as alfentanil increase propofol concentrations by reducing both the
      distribution and clearance of propofol. The pharmacokinetic interactions,
      however, are of relatively minor clinical importance compared with
      pharmacodynamic interactions. The pharmacodynamic interaction between propofol
      and other sedative agents, or one of the synthetic opioids, is synergistic. From
      the pharmacodynamic interaction data, optimal target propofol-opioid
      concentrations and optimal infusion regimens have been developed that ensure
      adequate anaesthesia in 50% and 95% of patients with the most rapid recovery
      possible. These optimal target propofol concentrations and infusion regimens are
      affected by the opioid with which propofol is combined, as well as the duration
      of infusion.

PMID- 9640114
TI  - Intravenous anaesthesia: manual infusion schemes versus TCI systems.
AB  - Propofol was first used to induce and maintain anaesthesia in the early 1980s.
      Several infusion regimens were described, some based on pharmacokinetic
      predictions. Advances in computing technology subsequently have allowed the
      development of portable target controlled infusion devices, with drugs delivered
      to achieve specific predicted target blood propofol concentrations. Assessments
      of propofol target controlled infusion systems in clinical practice and
      comparisons of 'Diprifusor' target controlled infusion systems with manual
      infusion are reviewed here.

PMID- 9640115
TI  - 'Diprifusor' for general and day-case surgery.
AB  - Total intravenous anaesthesia may be most beneficial for day-case surgery with
      regard to quality of recovery, lack of complications and the ability to sustain
      an efficient throughput of patients. However, the technique can be applied to all
      forms of surgery and, with a little practice, consistent results will be
      achieved. Computerised infusion pumps can be programmed to provide a target blood
      concentration that can be easily varied to alter the anaesthetic state. The
      commercially available 'Diprifusor', a target controlled infusion system for
      propofol, can facilitate the more widespread use of total intravenous techniques
      and allow their potential benefits to be applied and appreciated more widely.
      This review outlines some practical considerations that should enable a more
      confident approach to total intravenous techniques by anaesthetists who are
      unfamiliar with them.

PMID- 9640116
TI  - Use of 'Diprifusor' in anaesthesia for ophthalmic surgery.
AB  - A technique of balanced anaesthesia involving propofol infusions and a rapidly
      metabolised opioid offers advantages over traditional anaesthetic techniques for
      eye surgery. The most appropriate mode of delivery of propofol is by a
      'Diprifusor' target controlled infusion system. This paper discusses the use of a
      'Diprifusor' target controlled infusion system for eye surgery. Published data
      are reviewed and the results of a retrospective analysis of 138 successive eye
      surgery patients are presented.

PMID- 9640117
TI  - 'Diprifusor' for neurosurgical procedures.
AB  - The pharmacokinetic profile of propofol is an advantage in neurosurgery, where
      the rapid return of cognitive function is essential for an early postoperative
      assessment of neurological status. Administration of propofol by 'Diprifusor'
      target controlled infusion allows induction of anaesthesia in neurosurgical
      patients without significant reduction of mean arterial pressure or occurrence of
      apnoeic episodes. This short paper describes our experience of 'Diprifusor'
      target controlled infusion for neuroanaesthesia in a series of 20 patients
      undergoing craniotomy for excision of epileptic foci. The results have been
      compared with ten similar operations where propofol infusion was controlled
      manually.

PMID- 9640118
TI  - Future applications for TCI systems.
AB  - Infusion pumps incorporating 'Diprifusor' for the administration of propofol by
      target controlled infusion are now commercially available and are becoming more
      widely used. This paper considers possible future applications of target
      controlled infusion and summarises results obtained using prototype systems as a
      component of other control techniques and with other drugs. These include studies
      with patient-controlled systems for the administration of analgesia or sedation
      and a closed loop control system for the administration of propofol. Among
      currently available analgesic drugs, alfentanil and remifentanil are considered
      to be the most suitable for administration by target controlled infusion, but
      commercial systems for these agents are not yet available.

PMID- 9640119
TI  - Evaluation of the predictive performance of a 'Diprifusor' TCI system.
AB  - The predictive performance of a 'Diprifusor' target controlled infusion system
      for propofol was examined in 46 patients undergoing major surgery, divided into
      three age groups (18-40, 41-55 and 56-80 years). Measured arterial propofol
      concentrations were compared with values calculated (predicted) by the target
      controlled infusion system. Performance indices (median performance error and
      median absolute performance error) were similar in the three age groups, with
      study medians of 16.2% and 24.1%, respectively. Mean values for 'divergence' and
      'wobble' were -7.6%.h-1 and 21.9%, respectively. Measured concentrations tended
      to be higher than calculated concentrations, particularly following induction or
      an increase in target concentration. The mean (SD) propofol target concentration
      of 3.5 (0.7) micrograms.ml-1 during maintenance was lower in older patients,
      compared with higher target concentrations of 4.2 (0.6) and 4.3 (0.7)
      micrograms.ml-1 in the two younger age groups, respectively. The control of depth
      of anaesthesia was good in all patients and the predictive performance of the
      'Diprifusor' target controlled infusion system was considered acceptable for
      clinical purposes.

PMID- 9640120
TI  - Influence of pre-anaesthetic medication on target propofol concentration using a
      'Diprifusor' TCI system during ambulatory surgery.
AB  - The effects of pre-anaesthetic medication on target propofol concentration,
      induction dose, time to induction, and discomfort on infusion were studied in 45
      female patients undergoing ambulatory gynaecological procedures using
      'Diprifusor' target controlled infusion of propofol. The patients were randomly
      allocated to receive either no premedication (group 1) or premedication with
      diazepam alone (group 2) or in combination with alfentanil (group 3). Induction
      was more successful in premedicated than unpremedicated patients with an initial
      target propofol concentration of 4 micrograms.ml-1 (87% in group 2 and 93% in
      group 3 vs. 38% in group 1, p < 0.01). Premedication was also associated with the
      requirement of a lower mean target concentration for induction, a lower induction
      dose and a shorter time to induction. There were no significant between-group
      differences in discomfort on infusion or target concentration during maintenance.
      For short ambulatory procedures, the recommended initial target concentration of
      propofol is 4 micrograms.ml-1 in premedicated and 6 micrograms.ml-1 in
      unpremedicated patients.

PMID- 9640121
TI  - Influence of analgesic supplementation on the target propofol concentrations for
      anaesthesia with 'Diprifusor' TCI.
AB  - Forty healthy patients undergoing orthopaedic surgery were randomly allocated to
      receive an initial blood propofol target concentration of either 4 micrograms.ml
      1 or 6 micrograms.ml-1 for induction of anaesthesia with a 'Diprifusor' target
      controlled infusion system for propofol, and analgesic supplementation with
      either nitrous oxide 67% in oxygen or alfentanil 15-20 micrograms.kg-1.h-1.
      Anaesthesia was induced within 3 min in 80% and 95% of patients with propofol
      target concentrations of 4 micrograms.ml-1 and 6 micrograms.ml-1, respectively.
      The frequency of discomfort on infusion was similar for both target
      concentrations. During maintenance, supplementary doses of alfentanil were
      required to provide adequate surgical conditions in approximately half of the
      patients receiving nitrous oxide. There was no statistically significant
      difference between the target concentration [mean (SD)] of propofol for total
      intravenous anaesthesia [5.1 (2.0) micrograms.ml-1] compared with a technique
      using nitrous oxide [4.6 (1.2) micrograms.ml-1] supplemented as needed with small
      doses of alfentanil.

PMID- 9640122
TI  - Influence of ventilatory mode on target concentrations required for anaesthesia
      using a 'Diprifusor' TCI system.
AB  - This study examined the influence of mode of ventilation (spontaneous or
      controlled) on the target blood concentrations required to maintain anaesthesia
      with 'Diprifusor' (a target controlled infusion system for propofol) in 40
      healthy, unpremedicated, adult patients undergoing knee arthroscopy. All patients
      were given alfentanil (10 micrograms.kg-1) and ketorolac (10 mg) immediately
      before induction and all received a 2:1 mixture of nitrous oxide:oxygen. An
      initial target blood concentration of propofol of 6.0 micrograms.ml-1 was used in
      most patients to induce anaesthesia. The blood target concentration required to
      produce acceptable anaesthetic conditions was not significantly influenced by the
      mode of ventilation. The mean maintenance target concentration for propofol was
      3.9 (SD 0.83) micrograms.ml-1 in the ventilated group and 3.5 (SD 0.82)
      micrograms.ml-1 in the group of patients breathing spontaneously.

PMID- 9640123
TI  - TCI compared with manually controlled infusion of propofol: a multicentre study.
AB  - This prospective, randomised multicentre study was designed to determine the
      clinical profile of 'Diprifusor' target controlled infusion compared with
      manually controlled infusion of propofol in 562 patients, aged 18-85 years, in a
      range of surgical procedures in 29 centres. The dose of propofol required for
      loss of consciousness was statistically significantly lower in the target
      controlled infusion group [1.69 (0.50) vs. 2.31 (0.75) mg.kg-1, p < 0.001] but
      the overall rate of propofol administration was slightly, but significantly,
      higher [12.1 (5.1) vs. 11.0 (6.0) mg.kg-1.h-1, p < 0.05]. The target
      concentration (CT) required for induction decreased with increasing age and ASA
      class, with premedication and with the administration of an opioid before
      induction. However, the amount of opioid given did not influence the CT required
      for induction, but enhanced the haemodynamic effects of propofol induction in
      both groups. Most investigators expressed an overall preference for target
      controlled infusion (93%) and found it easier to use (76%). Despite the lack of
      experience of most investigators in using target controlled infusion, the
      clinical profiles of both propofol administrations were similar. Data suggest
      that the clinical profile of target controlled infusion may be improved with
      experience, for example by more active titration of CT to effect. Target
      controlled infusion may well become the preferred choice for anaesthetists.

PMID- 9640124
TI  - Gene therapy in autoimmune diseases.

PMID- 9640125
TI  - Can non-fundable trials be conducted anyway? The case for open, randomised,
      actively controlled trials in rheumatology.

PMID- 9640126
TI  - Unexplained hip pain: look beyond the obvious abnormality.

PMID- 9640127
TI  - Do the radiological changes of classic ankylosing spondylitis differ from the
      changes found in the spondylitis associated with inflammatory bowel disease,
      psoriasis, and reactive arthritis?
AB  - OBJECTIVE: In 1971 McEwen and colleagues suggested that the radiological changes
      of classic ankylosing spondylitis (AS), and the changes of the spondylitis
      associated with inflammatory bowel disease differ in several respects from the
      radiological features of psoriatic and reactive spondylitis. The findings of this
      study have never been confirmed. The aim of this study was to replicate the
      McEwen study comparing films blinded to diagnostic group. METHODS: The study
      population comprised 91 patients with classic AS, 15 patients with regional
      enteritis, 16 patients with ulcerative colitis, five patients with sexually
      acquired reactive arthritis, two with post-dysenteric arthritis, and 34 with
      psoriatic arthritis. Blinded reading of spinal radiographs was undertaken,
      scoring for severity, symmetry, paravertebral ossification, size of
      syndesmophytes, ligamentous calcification, squaring, discitis, pseudofractures,
      zygoapophyseal joint involvement, and complete ankylosis. RESULTS: Comparison of
      the four groups--classic, enteropathic, psoriatic, and reactive AS--showed
      differences with respect to symmetry of sacroiliitis, symmetry of lumbar spinal
      involvement, and frequency and size of syndesmophytes. Zygoapophyseal joint
      involvement was more frequent in the lumbar spine in classic and enteropathic
      spondylitis but no between group differences were found with respect to
      symphisitis, squaring, apophyseal joint involvement and ligamentous calcification
      in the lumbar spine, and other areas. CONCLUSIONS: Some of the radiological
      differences described by McEwen et al, notably the asymmetry, the less severe
      changes, and the distinctive syndesmophytes in psoriasis, have been confirmed. A
      number of phypotheses are proposed to explain these differences including
      biomechanical, biochemical, and genetic factors.

PMID- 9640128
TI  - Clinical spectrum associated with positive ANCA titres in 94 consecutive
      patients: is there a relation with PR-3 negative c-ANCA and
      hypergammaglobulinaemia?
AB  - OBJECTIVE: To calculate the positive predictive value (ppv) of cytoplasmic
      antineutrophil cytoplasmic antibodies (c-ANCAs) and anti-proteinase 3 (PR 3)
      antibodies for Wegener's granulomatosis (WG) and to evaluate their association
      with other diseases. METHODS: The clinical files of all 94 patients who had a
      positive c- or perinuclear (p)-ANCA test, or both, in the laboratory of the
      University Hospital, Leuven between April 1995 and March 1996 and who attended
      the Internal Medicine Department of the hospital were retrospectively studied.
      RESULTS: Of the 94 patients with ANCAs (fluorescence titre > or = 1/40), 57 were
      c-ANCA positive and 45 p-ANCA positive (eight were simultaneously c- and p-ANCA
      positive). Of the 57 c-ANCA positive patients, 23 had WG. The ppv for WG thus was
      40%. This value did not increase by defining a higher threshold for a positive
      ANCA. There was not a good relation between ANCA titres and disease activity in
      the WG patients, nor was there a relation between anti-PR 3 antibody levels and
      WG disease activity. The ppv of anti-PR 3 antibodies for WG however was very high
      (85%). There was a positive correlation between the level of (hyper)
      gammaglobulinaemia and c-ANCA titres in those patients with final diagnoses not
      known to be associated with c-ANCA. Forty five patients had positive p-ANCAs. The
      largest group were those with inflammatory bowel disease (n = 20, of whom the
      majority had colitis ulcerosa or primary sclerosing cholangitis, or both); the
      great majority of these patients had no anti-myeloperoxidase antibodies.
      Vasculitis was present in eight patients, of whom two had WG (both were also c
      ANCA positive). CONCLUSION: There is a low ppv of c-ANCAs for WG, caused by a
      high percentage of PR 3 negative, positive c-ANCA determinations, possibly
      related to hypergammaglobulinaemia. Anti-PR 3 antibodies have a high ppv for WG.
      However, neither c-ANCA titre, nor the level of anti-PR 3 antibodies correlated
      with the activity of the disease.

PMID- 9640129
TI  - Effects of patient education on compliance with basic treatment regimens and
      health in recent onset active rheumatoid arthritis.
AB  - OBJECTIVES: To determine the effects of patient education on compliance and on
      health in patients with active, recent onset rheumatoid arthritis (RA). METHODS:
      A randomised, controlled, assessor blinded, one year trial. The experimental
      group followed an education programme. All patients started on sulphasalazine
      therapy. Compliance with sulphasalazine was measured by pill counting. Compliance
      rates with regimens of physical exercise, endurance activities, and energy
      conservation were measured by questionnaires. Compliance with prescriptions of
      joint protection was scored using a test for joint protection performance. Health
      was measured by a Disease Activity Score (function of erythrocyte sedimentation
      rate, Ritchie score, and number of swollen joints), C reactive protein, Dutch
      AIMS scores, and M-HAQ scores, range of motion of shoulder, elbow, and knee
      joints. Parameters were scored at baseline and after three, six, and 12 months.
      RESULTS: Sixty of 65 patients gave informed consent, five of them withdrew from
      follow up. Compliance with sulphasalazine exceeded 80% with no differences
      between groups. Compliance with physical exercise (at three months), energy
      conservation (at three and at 12 months), and joint protection (at three months)
      improved significantly more in the experimental group. The improvements of health
      were not different in the groups. CONCLUSION: Compliance with sulphasalazine
      among patients with active, recent onset RA is high, whether formal patient
      education is followed or not. Compliance with physical exercise, energy
      conservation, and joint protection was increased by patient education. Formal
      patient education did not improve health status.

PMID- 9640130
TI  - Quantitative assessment of the rheumatoid synovial microvascular bed by
      gadolinium-DTPA enhanced magnetic resonance imaging.
AB  - OBJECTIVE: To examine the relation between rate of synovial membrane enhancement,
      intra-articular pressure (IAP), and histologically determined synovial
      vascularity in rheumatoid arthritis, using gadolinium-DTPA enhanced magnetic
      resonance imaging (MRI). METHODS: Dynamic gadolinium-DTPA enhanced MRI was
      performed in 31 patients with knee synovitis (10 patients IAP study, 21 patients
      vascular morphometry study). Rate of synovial membrane enhancement was quantified
      by line profile analysis using the image processing package ANALYZE. IAP was
      measured using an intra-compartmental pressure monitor system. Multiple synovial
      biopsy specimens were obtained by a blind biopsy technique. Blood vessels were
      identified immunohistochemically using the endothelial cell marker QBend30 and
      quantified (blood vessel numerical density and fractional area). RESULTS: Median
      blood vessel numerical density and fractional area were 77.5/mm2 (IQR; 69.3
      110.7) and 5.6% (IQR; 3.4-8.5) respectively. The rate of synovial membrane
      enhancement (median 2.74 signal intensity units/s, IQR 2.0-3.8) correlated with
      both blood vessel numerical density (r = 0.46, p < 0.05) and blood vessel
      fractional area (r = 0.55, p < 0.02). IAP did not influence the rate of
      enhancement. CONCLUSIONS: Gadolinium-DTPA enhanced MRI may prove to be a valuable
      technique for evaluating drugs that influence angiogenesis.

PMID- 9640131
TI  - Rheumatoid synovial endothelial cells secrete decreased levels of tissue
      inhibitor of MMP (TIMP1).
AB  - OBJECTIVES: Angiogenesis (the formation of new blood vessels) is a major
      component of the inflammatory pannus in rheumatoid arthritis (RA). Matrix
      metalloproteinase (MMP) secretion by microvascular endothelial cells is an
      essential step in angiogenesis. The secretion of MMP1, MMP2, MMP9, and TIMP1 by
      human microvascular endothelial cells derived from RA synovium (RASE) to normal
      synovium (NSE) and neonatal foreskin (FSE) was compared. METHODS: Confluent
      monolayers of endothelial cells in basal medium were pre-incubated for 24 hours
      in the presence or absence of phorbol myristate acetate (PMA, 100 ng/ml). MMP1
      activity was measured using a spectrophotometric assay and western blotting. MMP2
      and MMP9 were measured using zymography. TIMP1 was measured by enzyme linked
      immunosorbent assay and western blotting. RESULTS: There was little difference
      between the amounts of MMP2 secreted by any of the cell lines. In response to PMA
      both synovial cell types showed a significantly higher MMP1 and MMP9 activity
      compared with FSE, although there was no difference between RASE and NSE. Tumour
      necrosis factor alpha had minimal effect on MMP activity. There was a striking
      decrease in the amount of TIMP1 secreted by RASE compared with normal synovium.
      CONCLUSIONS: As overall MMP activity is a balance between the amount of MMP and
      TIMP1 present, the low levels of TIMP1 produced by RASE would shift the balance
      in favour of increased MMP activity by these cells. This is likely to contribute
      to the angiogenic potential of RASE.

PMID- 9640132
TI  - Inactivation of antithrombin III in synovial fluid from patients with rheumatoid
      arthritis.
AB  - OBJECTIVE: To investigate the thrombin inhibitory capacity of antithrombin III in
      the inflamed human joint. METHODS: Thrombin inhibitory capacity was measured,
      using a kinetic spectophotometric method, in matched plasma and synovial fluid
      samples of patients with rheumatoid arthritis (n = 22) and osteoarthritis (n =
      16), together with normal control plasma samples (n = 13). In the same samples,
      the concentration of antithrombin III was also determined by the method of radial
      immunodiffusion. The combination of these measurements allowed the calculation of
      the specific thrombin inhibitory capacity of these samples. RESULTS: An increased
      concentration of antithrombin III in rheumatoid compared with osteoarthritic
      synovial fluid was noted (p < 0.05). However, there was a significant depression
      in the specific activity of antithrombin III in rheumatoid synovial fluid when
      compared with matched plasma samples (p < 0.001) or with osteoarthritic synovial
      fluid (p < 0.05). CONCLUSION: In rheumatoid synovial fluid the thrombin
      inhibitory capacity of antithrombin III is disproportionately depressed relative
      to the concentration of antithrombin III, indicating the inactivation of
      antithrombin III in the rheumatoid joint.

PMID- 9640133
TI  - The occurrence of falls among patients with a new episode of hip pain.
AB  - OBJECTIVES: To establish the risk of falling among those who consult their
      general practitioner with a new episode of hip pain and to discover if risk is
      altered by age and according to whether, at presentation, signs of osteoarthritis
      are present on radiography. METHODS: A case-control study was conducted. Cases
      were all patients who presented with a new episode of hip pain to participating
      general practices throughout the United Kingdom. All cases had a pelvic
      radiograph taken on recruitment to the study. Three controls were matched for
      sex, age, and general practice to each case. A questionnaire was sent by post to
      all cases and controls. The risk of having fallen in the past 12 months among
      cases and controls was compared. RESULTS: The study included 111 cases presenting
      with hip pain and 229 controls who had not consulted with hip pain in the
      previous 12 months. Women (odds ratio = 3.6, 95% CI 1.9, 6.7) but not men (odds
      ratio = 0.8, 95% CI 0.3, 2.3) reported an increased risk of falling in the
      previous 12 months. Similar results were obtained when the previous four months
      were considered. For all cases, hip pain predated any reported falls. The
      increased risk in women was found particularly for those aged less than 70. Risk
      of falling was not altered by the presence of radiological changes of
      osteoarthritis. CONCLUSIONS: Hip pain, which may be a symptom of osteoarthritis
      of the hip, increases the risk of falling. This finding has implications for the
      advice offered by general practitioners to patients who consult with early hip
      pain.

PMID- 9640134
TI  - Multiple extra-articular synovial cyst formation: case report and review of the
      literature.
AB  - OBJECTIVE: To investigate the clinical manifestations and the treatment strategy
      of a very rare entity of disease manifesting as multiple extra-articular cystic
      synovitis with recurrent polyarthralgia. METHODS: A 47 year old male patient with
      multiple extra-articular synovial cysts was followed up prospectively for 13
      years. The clinical manifestations and response to various treatments were
      recorded. Comparisons are made among the five reported cases (including the
      present case). RESULTS: Multiple synovial cysts over the tendon sheath and bursae
      appeared successively with and without antecedent growth of nodules during 13
      years of follow up. Although polyarthralgia and high titred rheumatoid factor
      persisted throughout the course, there were no roentgenographical changes of
      joints specific to rheumatoid arthritis (RA). The synovial cysts and arthralgia
      failed to respond to any of the disease modifying anti-rheumatic drugs (DMARDs)
      prescribed. Systemic involvements such as pulmonary interstitial fibrosis and
      skin ulcers were also noted, but they were not progressive. CONCLUSIONS: Multiple
      extra-articular cystic synovitis is an uncommon disease entity closely related to
      RA. It has been reported exclusively in Japanese subjects and therefore some
      cultural factors, either genetic or environmental, may contribute to its
      development.

PMID- 9640135
TI  - Fatal vascular occlusion in juvenile dermatomyositis.

PMID- 9640136
TI  - Polyarteritis nodosa associated with precore mutant hepatitis B virus infection.

PMID- 9640137
TI  - Polymyalgic presentation of Sjogren's syndrome: a report of three patients.

PMID- 9640138
TI  - Duration of methotrexate treatment until partial and total remission of
      refractory juvenile rheumatoid arthritis.

PMID- 9640139
TI  - Lipid profiles in patients with rheumatoid arthritis.

PMID- 9640140
TI  - Smoking, rheumatoid factors, and rheumatoid arthritis.

PMID- 9640141
TI  - Pain after amputation: is prevention better than cure?

PMID- 9640142
TI  - Onset times and intubating conditions.

PMID- 9640143
TI  - Does ketorolac cause postoperative renal failure: how do we assess the evidence?

PMID- 9640144
TI  - Ventilatory assistance and respiratory muscle activity. 1: Interaction in healthy
      volunteers.
AB  - We have investigated the response of 12 normal, healthy subjects to resistance
      loading and ventilator assistance of spontaneous breathing. Three ventilators,
      the Hamilton Veolar, Engstrom Erica and Puritan Bennett 7200, were used to
      provide synchronized intermittent mandatory ventilation and two levels of
      pressure assistance. Total respiratory elastance and resistance were measured.
      The equivalent (negative) pressure of respiratory muscle activity (pmus) was then
      calculated from measurement of flow and pressure at the mouth. With ventilatory
      assistance, subjects maintained frequency, decreased inspiratory time and the
      magnitude of pmus, but increased tidal volume, thus not taking full advantage of
      ventilatory assistance. The waveform of pmus varied in detail within and between
      subjects and conditions, but the all-subject mean waveforms showed for all
      conditions a consistency of trajectory. Increasing the level of assistance
      decreased the duration and hence the (negative) peak value of pmus. The results
      suggest that some waveforms of flow or pressure from the ventilators may be more
      acceptable to patients than others, and that different patients may prefer
      different waveforms.

PMID- 9640145
TI  - Ventilatory assistance and respiratory muscle activity. 2: Simulation with an
      adaptive active ("aa" or "a-squared") model lung.
AB  - The aim of this study was to develop a lung model which adapted its active
      simulation of spontaneous breathing to the ventilatory assistance it received--an
      "aa" or "a-squared" lung model. The active element required was the waveform of
      negative pressure (pmus), which is equivalent to respiratory muscle activity.
      This had been determined previously in 12 healthy volunteers and comprised a
      contraction phase, relaxation phase and expiratory pause. Ventilatory assistance
      had shortened the contraction and relaxation phases without changing their shape,
      and lengthened the pause phase to compensate. In this study, the contraction and
      relaxation phases could be adequately represented by two quadratic equations, in
      addition to a third to provide a smooth transition. Therefore, the adaptive
      element required was the prediction of the duration of the contraction phase. The
      best predictive variables were flow at the end of contraction or peak mouth
      pressure. Determination of either of these allowed adjustment of the "standard"
      waveform to the level of assistance produced by an "average" ventilator, in a
      manner that matched the mean response of 12 healthy conscious subjects.

PMID- 9640146
TI  - Effect of different doses of inhaled nitric oxide on pulmonary capillary pressure
      and on longitudinal distribution of pulmonary vascular resistance in ARDS.
AB  - Inhaled nitric oxide lowers pulmonary capillary pressure (PCP) in animals and in
      patients with acute respiratory distress syndrome (ARDS). A dose-response
      relationship in patients with ARDS has not yet been established. Therefore, we
      studied the effects of four concentrations of nitric oxide (1, 10, 20 and 40
      volumes per million (vpm)) in random order, on PCP in 19 patients with ARDS. PCP
      was estimated by visual analysis of the pressure decay curve after balloon
      inflation of the pulmonary artery catheter. Haemodynamic and gas exchange
      variables were measured at each nitric oxide concentration. Patients were
      classified as responders when PCP decreased by at least 2 mm Hg after nitric
      oxide 20 vpm. In responders (n = 8), nitric oxide decreased PCP and post
      capillary vascular resistance dose-dependently and changed longitudinal
      distribution of pulmonary vascular resistance with a maximum effect at 20 vpm. In
      non-responders (n = 11), PCP did not change. In both groups, the nitric oxide
      induced decrease in pre-capillary vascular resistance was small with a maximum
      effect at 1 vpm. In ARDS, vasodilatation of pre-capillary vessels is achieved at
      low concentrations of nitric oxide, whereas the effect of nitric oxide on
      postcapillary vessels is variable. Higher concentrations may be required for
      optimal post-capillary vasodilatation in a subgroup of ARDS patients.

PMID- 9640147
TI  - Influence of surgical technique on early postoperative hypoxaemia in children
      undergoing elective palatoplasty.
AB  - We have assessed the influence of different surgical procedures on the incidence,
      severity and duration of early postoperative hypoxaemia in 312 healthy infants
      and children undergoing elective palatoplasty. Group 1 patients underwent von
      Langenbeck palatoplasty (n = 149), group 2 patients underwent push-back
      palatoplasty (n = 124) and group 3 patients underwent combined push-back
      palatoplasty and superior pharyngeal flap surgery (n = 39). Arterial oxygen
      saturation (SpO2) was recorded while patients were breathing air shortly after
      arrival in the recovery room (0 min), and at 5, 10, 15, 20, 30, 40, 50, 60, 120
      and 180 min thereafter. Patients who underwent more complex surgical techniques
      for palatoplasty had lower postoperative SpO2 values, slower recovery of SpO2 and
      a higher incidence of hypoxaemia during the early postoperative period. There
      were significant differences in postoperative SpO2, values and the incidence of
      hypoxaemia. The incidences of hypoxaemia and severe hypoxaemia were 27% and 1%,
      respectively, in group 1, 37% and 12% in group 2, and 36% and 33% in group 3.
      Hypoxaemia occurred most commonly in the first 15 min in children after von
      Langenbeck palatoplasty, in the first 40 min after push-back palatoplasty and in
      the 120 min after combined push-back palatoplasty and superior pharyngeal flap
      surgery. There were significant associations between low SpO2 values, incidence
      of hypoxaemia on admission to the recovery room and recovery scores.

PMID- 9640148
TI  - Sevoflurane compared with halothane for tracheal intubation in children.
AB  - We have studied 40 healthy children, aged 3-10 yr, undergoing adenotonsillectomy,
      in a double-blind, randomized study. Intubating conditions were assessed when the
      pupils had become small and central after inhalation induction with either 5%
      halothane and 60% nitrous oxide in oxygen or 8% sevoflurane and 60% nitrous oxide
      in oxygen. The quality of tracheal intubation was graded according to ease of
      laryngoscopy, position of the vocal cords, coughing, jaw relaxation and movement
      of limbs. Fewer children had significant vocal cord movement on laryngoscopy (P <
      0.01) and more had ideal intubating conditions when halothane was used (12 of 20
      compared with seven of 20; ns). Time to reach the clinical end-point for
      intubation was reached sooner with halothane (P = 0.015). In all children the
      trachea was intubated successfully at the first attempt and all remained
      haemodynamically stable throughout induction.

PMID- 9640149
TI  - Induction and emergence in infants less than 60 weeks post-conceptual age:
      comparison of thiopental, halothane, sevoflurane and desflurane.
AB  - We have studied 40 infants with a post-conceptual age of less than 60 weeks
      undergoing general anaesthesia for herniotomy. Patients were anaesthetized with 1
      MAC equivalent values for age and agent and allocated randomly to receive
      halothane, savoflurane or thiopental for induction, and halothane, sevoflurane or
      desflurane for maintenance of anaesthesia. At induction, both time to acceptance
      of a face mask and loss of eyelash reflex were recorded. Emergence times were
      noted by a blinded observer. Induction and emergence times were similar between
      the halothane and sevoflurane groups but were consistently shorter in the
      desflurane group compared with the halothane or sevoflurane groups. There were no
      problems at extubation or significant apnoea in any group. Induction of
      anaesthesia in this population was no quicker with sevoflurane than with
      halothane and the method used for induction did not influence recovery time.
      Maintenance of anaesthesia with desflurane resulted in a shorter recovery time in
      infants in whom anaesthesia was induced with halothane or thiopental. Desflurane
      maintenance may be particularly beneficial in the neonate.

PMID- 9640150
TI  - Surgical/tourniquet pain accelerates blood coagulability but not fibrinolysis.
AB  - Tissue damage during surgery induces coagulation factors and activates platelets.
      Surgical pain may provoke release of catecholamines, leading to
      hypercoagulability. We have investigated the effect of surgical pain on blood
      coagulability and fibrinolysis in orthopaedic operations using tourniquets in 22
      patients undergoing total knee replacement. Patients were allocated to one of two
      groups to receive extradural anaesthesia (EA; n = 11) or general anaesthesia (GA;
      n = 11). The EA group received lumbar extradural block with lidocaine. The GA
      group received only general anaesthesia, maintained with 1.5-2.5% sevoflurane and
      66% nitrous oxide in oxygen. Using a thrombelastogram technique, blood
      coagulability and fibrinolysis were measured. Mean maximum amplitude (MA), which
      reflects coagulability, increased after tourniquet inflation (11%) in group GA
      whereas MA in group EA did not change. After tourniquet deflation, MA values in
      both GA and EA groups increased significantly (10% and 20%, respectively) (P <
      0.05), and there was also a significant difference in MA between groups (P <
      0.05). The fibrinolytic rate did not change in either group during tourniquet
      inflation, but increased significantly (160%) after tourniquet deflation. There
      was no significant difference in fibrinolytic rate between the groups. We
      conclude that the hypercoagulability seen in group GA could have been caused by
      surgical or tourniquet pain, or both, and that extradural anaesthesia is a useful
      technique to prevent hypercoagulability.

PMID- 9640151
TI  - Changes in specific markers of haemostasis during reduction mammoplasty.
AB  - We have investigated the time course of the coagulation and fibrinolytic changes
      during moderate surgical trauma (elective reduction mammoplasty) in the absence
      of other confounding factors that could affect haemostasis. Specific markers for
      coagulation (prothrombin fragment 1.2 (F1.2), thrombin-antithrombin III complex
      (TAT)) and fibrinolysis (plasmin-antiplasmin complex (PAP) and D-dimer) were
      examined. Blood samples were obtained in 20 ASA I anaesthetized female patients
      at T0 (before operation), T75 (during operation) and T150 (before the end of
      operation). There was a progressive increase in blood loss during operation:mean
      110 (SD 80) ml at T75 and 470 (180) ml at T150. This was associated with a
      significant increase in plasma concentrations of F1.2, PAP and D-dimer at T150
      only (P < 0.05 vs T0). We conclude that moderate surgical trauma with blood
      losses greater than 300 ml can activate thrombin generation and fibrinolysis
      during operation.

PMID- 9640152
TI  - Effect of remifentanil on the haemodynamic response to orotracheal intubation.
AB  - We have examined the effect of remifentanil on the haemodynamic response to
      orotracheal intubation in a randomized, double-blind study. We studied 40
      patients allocated to one of four groups of 10 each, to receive the following
      immediately before induction of anaesthesia: remifentanil 1 microgram kg-1 bolus
      over 30 s, followed by an infusion of 0.5 microgram kg-1 min-1; saline placebo
      only; glycopyrrolate 200 micrograms and remifentanil 1 microgram kg-1 bolus over
      30 s, followed by an infusion of 0.5 microgram kg-1 min-1; or glycopyrrolate 200
      micrograms only. Anaesthesia was induced with propofol, vecuronium and 1%
      isoflurane with 66% nitrous oxide in oxygen. The trachea was intubated under
      direct laryngoscopy 3 min after induction of anaesthesia. Arterial pressure and
      heart rate were measured non-invasively, immediately before induction of
      anaesthesia and then at 1-min intervals. Remifentanil was found to effectively
      attenuate the pressor response to intubation (P < 0.05 for the increase in mean
      arterial pressure; P < 0.01 for the increase in heart rate). In the absence of a
      concurrent vagolytic agent, remifentanil was associated with bradycardia or
      hypotension, or both, in five of 10 patients, compared with one patient who
      received remifentanil and glycopyrrolate.

PMID- 9640153
TI  - Appropriate size and inflation of the laryngeal mask airway.
AB  - We have compared size 3 and size 4 laryngeal masks in 30 females and size 4 and
      size 5 in 30 males for success rate of insertion, incidence of airleak and
      pressure exerted on the pharynx. First, the ex vivo volume-pressure relationship
      of the mask was obtained. Second, after insertion of a mask, the cuff was
      inflated with the recommended maximum volume of air and intracuff pressure
      measured. Third, the incidence of airleak during a steady airway pressure of 18
      cm H2O was noted. Fourth, the cuff was deflated until it just prevented airleak,
      and cuff pressure was measured. The mask was removed, the other size was inserted
      and the same procedure repeated. At the end of operation, final in vivo and ex
      vivo pressures were measured. The pressure exerted on the pharynx was calculated
      as the difference between ex vivo and in vivo intracuff pressures. It was always
      possible to insert both sizes in both sexes. In females, airleak occurred in 15
      patients with the size 3 and in five patients with the size 4 (difference: P =
      0.005) and in males, 21 patients with the size 4 and in four patients with the
      size 5 (P < 0.001). Removal of air to the minimum effective volume significantly
      decreased intracuff pressure and pressure on the pharynx; on removal of the mask,
      pressures were similar to, or lower than, initial pressures. Therefore, a larger
      mask (size 4 in females and size 5 in males) provided a better seal than a
      smaller size without producing higher pressures on the pharynx.

PMID- 9640154
TI  - Changes in mucociliary activity may be used to investigate the airway-irritating
      potency of volatile anaesthetics.
AB  - We have examined the short-term effects of three volatile anaesthetics,
      halothane, isoflurane and desflurane, on mucociliary activity in the rabbit
      maxillary sinus in vivo. Mucociliary activity was recorded photoelectrically and
      the signal processed by fast Fourier transformation. Administration of 1.0 MAC of
      halothane, isoflurane or desflurane caused a temporary increase in mucociliary
      activity, with mean peak responses of 47.8 (SEM 13.0)%, 44.0 (9.6)% and 45.1
      (23.7)% (n = 6), respectively. The response to all three compounds was biphasic;
      an initial peak was observed within 2 min and a second peak at 3-8 min. The
      second response was not significant for halothane. In contrast, desflurane
      produced a significant second peak while the first was small and failed to reach
      significance. Halothane displayed an initial peak within 2 min which was blocked
      by atropine but not by the neurokinin 1 (NK1) receptor antagonist CP-99. The
      second peak at 3-5 min was less pronounced for halothane than for isoflurane or
      desflurane. The second peak was not affected by atropine pretreatment, but was
      blocked by pretreatment with CP-99. A combination of atropine and CP-99
      pretreatment abolished the mucociliary response to halothane. Atropine
      pretreatment did not affect, whereas CP-99 significantly reduced, the response to
      desflurane. We conclude that the NK1-mediated response was most pronounced for
      desflurane which is considered the most airway irritating compound of the three.
      It is likely that the size of the NK1-mediated response reflects the airway
      irritating properties of the volatile anaesthetic used.

PMID- 9640155
TI  - Cardiovascular effects of concomitant administration of isoflurane and nicorandil
      in dogs.
AB  - Nicorandil, a new KATP channel opener, is used in clinical practice for anti
      anginal therapy. It exhibits vasodilator properties as does the halogenated
      anaesthetic isoflurane. We have examined the cardiovascular effects of increasing
      concentrations of isoflurane after administration of nicorandil in 10 adult
      beagle dogs anaesthetized with thiopental and whose lungs were ventilated
      mechanically. During surgery, anaesthesia was maintained with 1.0-1.5%
      isoflurane. A left thoracotomy was performed and the heart suspended in a
      pericardial cradle. Monitoring included: ECG; aortic, left ventricular, arterial,
      central venous and pulmonary artery pressures; cardiac output; coronary flow; and
      segmental length in the apical region. After surgery, isoflurane anaesthesia was
      set at an end-tidal concentration of 1.05% (1 MAC) and measurements obtained;
      these were repeated with 1.4%, 1.75%, 2.1% and 1.05% isoflurane concentrations
      after appropriate stabilization periods. Nicorandil (100 micrograms kg-1 bolus,
      25 micrograms kg-1 min-1 infusion) was begun and a second dose-response study of
      isoflurane was obtained as before. Blood samples were obtained for measurement of
      concentrations of nicorandil. Systolic ventricular function was assessed by
      systolic shortening (%SS) and preload recruitable stroke work (PRSW). Increasing
      isoflurane concentration produced decreases in heart rate, systolic pressure,
      cardiac output, %SS and PRSW. Nicorandil produced a slight decrease in systolic
      arterial pressure (10 and 15 mm Hg after 1.05% and 2.05% isoflurane) and a slight
      increase in heart rate (10 and 5 beat min-1 after 1.05% and 2.05% isoflurane).
      Preload, assessed by end-diastolic length, decreased. Coronary blood flow
      increased with infusion of nicorandil. Left ventricular function was not affected
      by infusion of nicorandil. We conclude that nicorandil has only minor
      vaso/venodilatory effects in the presence of isoflurane. Ventricular function was
      not altered by infusion of nicorandil.

PMID- 9640156
TI  - Population based pharmacokinetic analysis: why do we need it; what is it; and
      what has it told us about anaesthetics?

PMID- 9640157
TI  - Leucocyte distribution during sevoflurane anaesthesia.
AB  - We have examined if sevoflurane anaesthesia per se modified the number of
      circulating leucocytes in humans. Fifty-nine patients undergoing elective surgery
      were anaesthetized with sevoflurane in oxygen. The inhaled concentration was
      increased gradually to 5% and maintained for 20 min. Arterial blood samples were
      obtained before induction of anaesthesia and at 20 min. While the total number of
      leucocytes remained constant, circulating neutrophils decreased (mean 3370 (SD
      1030) mm-3 to 3170 (940) mm-3; P < 0.01) and lymphocytes increased (1870 (520) mm
      3 to 2040 (580) mm-3; P < 0.01). We conclude that high concentrations of
      sevoflurane modified the distribution of leucocytes in anaesthetized patients.

PMID- 9640159
TI  - Caudal anaesthesia with 0.375% ropivacaine or 0.375% bupivacaine in paediatric
      patients.
AB  - We have determined the effectiveness and degree of motor block produced by the
      new local anaesthetic, ropivacaine, when used for caudal anaesthesia in children.
      We studied 60 children, aged 3-6 yr, ASA I, allocated randomly in a double-blind
      manner, to receive one of two local anaesthetics: 0.375% ropivacaine 1.0 ml kg-1
      or 0.375% bupivacaine 1.0 ml kg-1. Patients were anaesthetized with continuous
      infusion of propofol 200 micrograms kg-1 min-1. The lungs were ventilated with
      50% nitrous oxide in oxygen. Heart rate and arterial pressure were measured every
      5 min after administration of local anaesthetic until discharge from the recovery
      room. The extent of motor block in the recovery room was scored as 1-3. Adverse
      events and time to first analgesic requirements were recorded. Patients in the
      two groups did not differ in age, weight or height. There were no differences in
      heart rate or arterial pressure between the two groups. No adverse events were
      observed. The degree of motor block was significantly different between the two
      groups. The ropivacaine group showed a shorter duration of motor block than the
      bupivacaine group (P < 0.05). Postoperative analgesia was required at a mean time
      of 5 (SD 3.2) h in the ropivacaine group compared with 5 (2.8) h in the
      bupivacaine group. These findings suggest that caudal anaesthesia with
      ropivacaine in paediatric patients is effective and produces less motor block in
      the postoperative period.

PMID- 9640158
TI  - Thiopental or etomidate for rapid sequence induction with rocuronium.
AB  - We have assessed the effect of the choice of i.v. induction agent on intubation
      conditions, 60 s after administration of rocuronium 0.6 mg kg-1. We studied 60
      adult patients, allocated randomly to one of two groups. Anaesthesia was induced
      with alfentanil 10 micrograms kg-1 followed by thiopental 5 mg kg-1 (AT-R group;
      n = 30) or etomidate 0.3 mg kg-1 (AE-R group; n = 30). Both groups received
      rocuronium 0.6 mg kg-1. Laryngoscopy was started 60 s later and intubation
      conditions were evaluated according to a standard score, which considered ease of
      laryngoscopy, condition of the vocal cords and reaction to intubation. In the AT
      R group, overall intubation conditions were scored as excellent in 20 patients,
      good in nine and fair in the remaining patient. In the AE-R group, overall
      intubating conditions were excellent in 24 and good in six patients. The
      difference between the two groups was not significant. Of the three components of
      the intubation score assessed, response to intubation stimulus was significantly
      less pronounced in group AE-R compared with group AT-R (P < 0.05): group AE-R, no
      reaction in 24 patients, slight diaphragmatic movement in five and mild coughing
      in one patient; group AT-R, no reaction in 13, slight diaphragmatic movement in
      14, mild coughing in two and severe coughing in one patient. We conclude that
      etomidate as part of an induction regimen containing alfentanil and rocuronium
      attenuated the reaction to intubation to a greater extent than thiopental.

PMID- 9640160
TI  - Remifentanil in combination with propofol for spontaneous ventilation
      anaesthesia.
AB  - We have investigated the effect of four doses of remifentanil on the incidence of
      respiratory depression and somatic response at incision. Remifentanil was
      administered as a loading dose of 0.125, 0.25, 0.375 or 0.5 microgram kg-1 and at
      a maintenance infusion rate of 0.025, 0.05, 0.075 or 0.1 microgram kg-1 min-1,
      respectively, with an infusion of propofol 6 mg kg-1 h-1. Responses occurred in
      88% of patients with remifentanil 0.025 microgram kg-1 min-1 compared with 30-40%
      in the other groups. Respiratory depression after incision increased from 6% with
      remifentanil 0.025 microgram kg-1 min-1 to 73% with 0.1 microgram kg-1 min-1.
      Increases in propofol infusion rate to 7.2-8.4 mg kg-1 h-1 produced adequate
      maintenance of anaesthesia. Reductions in remifentanil doses to 0.025-0.05
      microgram kg-1 min-1 resulted in adequate respiration at the end of surgery in
      88% of patients. Maintenance infusions of the two drugs for spontaneous
      ventilation are likely to be in these ranges. However, the ideal loading doses
      and infusion rates for induction remain to be established.

PMID- 9640161
TI  - Extradural anaesthesia for caesarean section in a patient with syringomyelia and
      Chiari type I anomaly.
AB  - We describe elective Caesarean section performed under extradural anaesthesia in
      a parturient with symptomatic syringomyelia and coexisting Chiari type I anomaly.
      Syringomyelia is reviewed and the anaesthetic implications of the condition
      discussed. Anaesthesia should be directed primarily at avoidance of increased
      intracranial pressure, which can cause sudden deterioration in these patients.

PMID- 9640162
TI  - Anaesthetic management in patients suspected of, or at risk of, having
      Creutzfeldt-Jakob disease.
AB  - We report two young patients who had repeated neurosurgical procedures and who
      were thought to be at risk of developing Creutzfeldt-Jakob disease (CJD). The
      first patient had been given a lyophilized dural graft in the course of removal
      of a cerebellar medulloblastoma 15 yr previously. The second patient had received
      pituitary-derived growth hormone for treatment of growth hormone deficiency,
      secondary to a third ventricle teratoma, exised 13 yr earlier. The presence of
      cerebellar symptoms together with being recipients of growth hormone or dural
      graft of cadaveric extraction arose suspicion of a diagnosis of CJD in both
      individuals. Precautions in the anaesthetic and surgical management of these two
      patients are discussed, and pertinent literature is reviewed briefly.

PMID- 9640163
TI  - Minimally invasive coronary bypass surgery: postoperative pain management using
      intermittent bupivacaine infiltration.
AB  - Minimally invasive direct coronary artery bypass grafting (MIDCAB) is becoming a
      popular adjunct to standard cardiac bypass surgery in selected patients with
      accessible single or double vessel disease. However, the limited anterior
      thoracotomy used to access the heart involves trauma to the muscle tissue during
      removal of the fourth costal cartilage and a small piece of connected rib,
      perhaps leading to more severe postoperative pain compared with patients
      undergoing routine sternotomy. Intrathecal opioids can be used but have limited
      therapeutic duration and there is concern regarding anticoagulation. We present a
      case where soft tissue catheters were placed into the depths of the surgical
      wounds and pain was diminished greatly by intermittent regular infiltration with
      bupivacaine.

PMID- 9640164
TI  - Error in measurement of oxygen and carbon dioxide concentrations by the
      DeltatracII metabolic monitor in the presence of desflurane.
AB  - In experiments in dogs on the metabolic effects of inhalation anaesthetics, we
      noticed that in the presence of desflurane, oxygen uptake (VO2) measured with the
      Deltatracll metabolic monitor seemingly increased whereas it decreased when
      determined independently by the Fick principle. This difference remained even
      after correction for changes in gas concentration on addition of an inhalation
      anaesthetic. Therefore, we suspected that desflurane interferes with the
      measurement of gas concentrations. Using different precision gases, we found that
      desflurane disturbed both the paramagnetic oxygen sensor and the infrared carbon
      dioxide detector so that the measured oxygen (when FIO2 was > 0.21) and carbon
      dioxide concentrations were greater than expected. These errors multiply in the
      computing process of oxygen uptake by the DeltatracII. When the DeltatracII is to
      be used during inhalation anaesthesia, its results should be corrected for the
      presence of an anaesthetic gas. More importantly, corrections must also be made
      for measurement errors of the oxygen and carbon dioxide sensors, unless the
      device has been equipped with a modified (nickel membrane) oxygen sensor
      insensitive to the presence of volatile agents.

PMID- 9640165
TI  - Video-intuboscopy: a new aid to routine and difficult tracheal intubation.
AB  - Video-intuboscopy gives a video display of the view from the tip of the tracheal
      tube during conventional laryngoscopy, and was developed particularly to assist
      the immediate management of unexpected difficult intubation. A lightweight,
      malleable video-optical intubation stylet transmits the view from the stylet tip
      onto a monitor. It is inserted in the tracheal tube before starting anaesthesia,
      and the view from the tracheal tube tip enables the anaesthetist to verify
      tracheal tube position in the trachea. During difficult intubation the video view
      is used to guide the tracheal tube into the trachea. When used to allow
      confirmation of tracheal placement, the system did not interfere with
      conventional intubation procedures. The method showed the subglottic airway, gave
      immediate confirmation of tracheal tube position, and aided teaching and
      supervision. The method was used to guide intubation in two patients with
      unanticipated grade 3 laryngoscopic views. Intubation was simple, rapid and
      atraumatic, without the need for head, neck or laryngeal manipulation. Tracheal
      placement was instantly confirmed using the video view from the stylet tip.
      Clinical studies are required to define the value of this new intubation
      technique.

PMID- 9640166
TI  - Stimulus frequency in the detection of neuromuscular block in humans. 1970.

PMID- 9640167
TI  - Anaesthesia and the competence revolution.

PMID- 9640168
TI  - Anaesthesia and the competence revolution.

PMID- 9640169
TI  - Autologous blood transfusion.

PMID- 9640170
TI  - Propofol and electrophysiological variables during emergence from anaesthesia.

PMID- 9640171
TI  - Bronchospasm during inhalation of nebulized midazolam.

PMID- 9640172
TI  - Low-dose naloxone in the treatment of urinary retention during extradural
      fentanyl causes excessive reversal of analgesia.

PMID- 9640173
TI  - Extradural catheter-related infections in patients with infected cutaneous
      wounds.

PMID- 9640174
TI  - Extradural catheter-related infections in patients with infected cutaneous
      wounds.

PMID- 9640175
TI  - Colour imaging using a scanning laser ophthalmoscope.

PMID- 9640176
TI  - Macular holes--a diagnostic and therapeutic enigma?

PMID- 9640177
TI  - Why "orbital pseudotumour" is no longer a useful concept.

PMID- 9640178
TI  - Novel approach towards colour imaging using a scanning laser ophthalmoscope.
AB  - AIMS: Conventional fundus imaging using a fundus camera produces colour fundus
      pictures. The scanning laser ophthalmoscope (SLO) has the advantages of lower
      levels of light exposure, improved contrast, and direct digital imaging but until
      now has produced monochromatic images as a laser of single wavelength is used.
      True representation of the fundus is possible by combining images taken using
      blue, green, and red lasers. METHODS: A custom built SLO was used to capture
      blue, green, and red fundus images from suitable volunteers and patients with
      fundus disease. Images were corrected for eye movement and combined to form a
      colour image. Colour fundus photographs were taken using a fundus camera for
      comparison with the SLO image. RESULTS: The background fundus and retinal
      vasculature had similar appearances with the two imaging modalities. Internal
      limiting membrane reflections were prominent with the SLO. Identification of new
      vessels in the diabetic fundus was easier with the SLO than the colour fundus
      photographs. CONCLUSION: A colour SLO offers all the advantages of the present
      monochromatic imaging system with the added advantage of true colour
      representation of the fundus.

PMID- 9640179
TI  - Fundus autofluorescence in patients with macular holes imaged with a laser
      scanning ophthalmoscope.
AB  - AIM: To demonstrate the usefulness of a recently developed technique of imaging
      fundus autofluorescence and to compare it with the results of fluorescein
      angiography in the diagnosis and staging of macular holes. METHODS: The intensity
      and distribution of fundus autofluorescence was studied in 51 patients with
      idiopathic macular holes and pseudoholes using a confocal laser scanning
      ophthalmoscope (cLSO) and the images were compared with those obtained by fundus
      fluorescein angiography. RESULTS: Autofluorescence imaging demonstrated bright
      fluorescence of macular holes with appearance similar to that obtained by
      fluorescein angiography. In contrast macular pseuodoholes showed no such
      autofluorescence. The attached operculum in stage 2 macular holes and the
      preretinal operculum in stage 3 macular holes showed focal decreased
      autofluorescence. The associated retinal elevation and the cuff of subretinal
      fluid were less fluorescent compared with the background autofluorescence of the
      normal fellow eyes. Following successful surgical treatment the autofluorescence
      of the macular holes was no longer visible. CONCLUSION: Autofluorescence imaging
      with the cLSO makes the assessment of macular holes possible with an accuracy
      comparable with that of fluorescein angiography. Being non-invasive and rapid,
      autofluorescence imaging may become a useful alternative to fluorescein
      angiography in the assessment and the differential diagnosis of full thickness
      macular holes.

PMID- 9640181
TI  - Comparison of measurements of neuroretinal rim area between confocal laser
      scanning tomography and planimetry of photographs.
AB  - BACKGROUND: To compare neuroretinal rim area measurements by confocal scanning
      laser tomography and planimetric evaluation of optic disc photographs. METHODS:
      For 221 patients with primary and secondary open angle glaucoma, 72 subjects with
      ocular hypertension, and 139 normal subjects, the optic disc was morphometrically
      analysed by the confocal scanning laser tomograph HRT (Heidelberg retina
      tomograph) and by planimetric evaluation of stereo colour optic disc photographs.
      RESULTS: Absolute rim area and rim to disc area were significantly (p < 0.0001)
      larger with the HRT than with planimetric evaluation of photographs. Differences
      between the two methods were significantly (p < 0.01) larger in normal eyes with
      small cupping than in normal eyes with large cupping, and differences were
      significantly (p < 0.01) larger in glaucomatous eyes with marked nerve damage
      than in glaucomatous eyes with moderate nerve damage. Coefficients of
      correlations between rim measurements of both methods were R2 = 0.60 for rim to
      disc area and R2 = 0.33 for absolute rim area. Planimetric measurements of rim
      area correlated significantly (p < 0.05) better than HRT determinations of rim
      area with mean visual field defect and retinal nerve fibre layer visibility.
      CONCLUSIONS: Measurements of absolute rim area and rim to disc area are
      significantly larger with the HRT compared with planimetry of disc photographs.
      Differences between both methods depend on disc area, cup size and glaucoma
      stage. The reason may be that the HRT measures the retinal vessel trunk as part
      of the neuroretinal rim. The differences between both methods, which should be
      taken into account if disc measurements performed by both methods are compared
      with each other, may not influence the main advantage of the HRT--that is,
      morphological follow up examination of patients with glaucoma.

PMID- 9640180
TI  - Quantitative evaluation of the optic nerve head in early glaucoma.
AB  - AIMS: Progressive loss of neuroretinal rim tissue is known to occur early in
      glaucoma and measurement of the neuroretinal rim area is possible by
      magnification corrected analysis of optic disc photographs (planimetry). This
      study was performed to determine whether the facility to distinguish between
      glaucomatous and normal optic discs could be improved upon by: (a) taking into
      account the known relation between optic disc size and neuroretinal rim area, and
      (b) measuring rim area in a number of segments, in order to detect focal changes.
      METHODS: Planimetric examination of the optic disc photographs of 88 control
      subjects and 51 patients with early visual field defects was performed. In the
      control group, multiple linear regression analysis was performed between
      neuroretinal rim area and optic disc area, age, sex, eye side, refraction, and
      keratometry. This was repeated for the whole disc and for each of twelve 30
      degree segments. Normal ranges were defined by the 98% prediction intervals of
      the regression analysis and the sensitivity and specificity for correct
      identification of optic discs in the two groups determined. RESULTS: Multiple
      linear regression demonstrated significant associations between the neuroretinal
      rim area and optic disc area and age in normal subjects. Sensitivity and
      specificity for glaucoma diagnosis, using the cut off derived from the 98%
      prediction intervals, was 37.7% and 98.9% respectively when total neuroretinal
      rim area alone was considered, and 88.7% and 94.3% respectively when the 30
      degree segments were included. The most frequent pattern of neuroretinal rim loss
      was diffuse, followed by thinning in more than one sector and then by thinning in
      the inferotemporal sector alone. CONCLUSIONS: This method of optic disc analysis
      enables the examiner to identify glaucomatous optic discs at the stage of early
      perimetric loss with a high degree of precision. Optic disc photography is
      simple, and fundus cameras are widely available. This method for glaucoma case
      identification may therefore be suitable for the primary care setting as well as
      hospital practice.

PMID- 9640182
TI  - Optical coherence tomography of pneumatic displacement of optic disc pit
      maculopathy.
AB  - BACKGROUND: The authors have previously concluded that fluid from an optic disc
      pit creates an inner layer separation (ILS) of the retina. An outer layer
      detachment (OLD) centred on the macula is a secondary phenomenon that causes a
      dense central scotoma. Pneumatic displacement of the OLD effects an improvement
      in central vision. Pathology to confirm these conclusions is lacking.
      Intraretinal images obtained by optical coherence tomography (OCT), however, are
      confirmatory. METHODS: Three patients with optic disc pit maculopathy were
      studied with stereoscopic photographs, visual fields, and OCT before and after
      intravitreal gas was injected to displace the central retinal elevation to below
      the inferior temporal vascular arcade. RESULTS: Preoperatively, OCT demonstrated
      an ILS that connected with the optic disc pit. External to it was an OLD that
      centred on the fovea and did not connect with the optic disc pit. Pneumatic
      displacement of the OLD was accompanied by an improvement in central vision. Long
      term follow up indicates that the effect of displacement may be temporary.
      CONCLUSION: OCT confirmed the two layer structure of optic disc pit maculopathy
      and that the improvement in central vision after pneumatic displacement coincides
      with a reattachment of the OLD in the macula. It also supports the hypothesis
      that the ILS, which persists, provides a conduit for the continuous flow of fluid
      from the pit to the displaced retinal elevation.

PMID- 9640183
TI  - An alternative and more cost effective method of delivery of radiotherapy in age
      related macular degeneration.
AB  - AIMS/BACKGROUND: In the past 5 years there has been a dramatic increase in the
      use of radiotherapy to treat subfoveal neovascular membranes (NVMs) in both
      Europe and the USA despite the high cost. An alternative, more cost effective
      method of delivery using x ray simulation and bite block head fixation is
      described. METHOD: 15 patients were recruited with classic subfoveal NVMs. Head
      fixation was achieved with a customised Perspex mask for eight patients and a
      bite block for seven. An x ray simulator was used to check the field of
      irradiation. No computerised tomography (CT) was performed. All patients received
      a total dose of 13.3 Gy ionising radiation. Visual acuities were charted before
      and after treatment over a 24 month period. RESULTS: After 24 months, 5/8 (67%)
      in the mask group showed stable visual acuities (less than two line change on
      Snellen chart) compared with 3/7 (43%) in the bite block group. This difference
      may be attributed to a variation in the pretreatment visual acuities in the two
      groups. From several studies it has been estimated that 24 months after diagnosis
      28% untreated individuals would have stable vision compared with 53% patients in
      this study. CONCLUSIONS: These results compare favourably with other studies and
      show that teletherapy can be safe and effective form of treatment for subfoveal
      NVMs. The authors have described an alternative method of head fixation and shown
      that CT scanning is not essential. This method of delivery is considerably less
      costly than that traditionally used and may allow greater numbers of patients to
      benefit from radiotherapy treatment.

PMID- 9640184
TI  - Epithelial permeability reflects subclinical effects of contact lens wear.
AB  - AIMS: Recently, it was reported by the authors that a single drop
      fluorophotometric technique for estimating corneal epithelial permeability (Pde)
      to fluorescein is not sufficiently precise for monitoring permeability changes in
      individual patients., but may be useful for evaluating mean differences in Pdc in
      population based research. To determine whether this technique provides a more
      sensitive index of epithelial integrity compared with conventional clinical
      assessments, the effects of mild corneal trauma on Pdc, the slit lamp appearance
      of the cornea, and corneal thickness (CT) were assessed. METHODS: After baseline
      slit lamp examinations (SLE) and CT measurements, one randomly chosen eye of each
      of 32 normal subjects underwent 1 hour of closed eye soft contact lens (CL) wear
      while the fellow eye served as a control (no CL). After removing the CL, the SLE
      and CT measurements were repeated. Then, Pdc to fluorescein was assessed using a
      single drop fluorophotometric method refined to enhance feasibility, precision,
      and accuracy. RESULTS: The mean (95% confidence interval) difference in natural
      log (Pdc) between 32 pairs of eyes (CL minus no CL) was 0.341 (0.069, 0.613), p =
      0.016. By contrast, none of the 32 subjects exhibited corneal epithelial
      disruption upon SLE with white light following the closed eye period. Also, no
      substantial differences were apparent in the corneal swelling response between
      paired eyes, mean delta CT (95% CI) = -2.31(-7.53, 2.91) microns, p = 0.37.
      CONCLUSIONS: Pdc measurements, used in studies of modest sample size, appear
      capable of detecting average differences in corneal barrier function that remain
      undetectable by SLE or pachymetry.

PMID- 9640185
TI  - Donor organ cultured corneal tissue selection before penetrating keratoplasty.
AB  - AIMS: Donor organ cultured corneal tissue selection before penetrating
      keratoplasty is carried out by taking into account different variables. The
      objective was to identify preoperative variables which are significantly and
      independently associated with transplant outcome and should effectively be taken
      into account before transplantation. METHODS: 231 consecutive penetrating
      keratoplasties were prospectively studied using organ cultured tissue.
      Morphometric analysis of the donor corneal endothelium was performed before
      transplantation. Graft survival and endothelial cell density, during the second
      year following transplantation, were studied both at a univariate and
      multivariate level. RESULTS: Recipient age, recipient rejection status, and
      preoperative diagnosis significantly influenced graft survival. Graft survival
      was higher when using corneal tissue from donors older than 80 years.
      Postoperative endothelial density decreased with preservation time and
      coefficient of variation after preservation. It increased with endothelial cell
      density after preservation and deswelling time, and correlated with preoperative
      diagnosis. CONCLUSION: Organ cultured corneas with endothelial cell density after
      preservation < 2000 cells/mm2, and high coefficient of variation, may be
      discarded before transplantation. Corneas should be preserved for less than 3
      weeks, and allowed to deswell before transplantation for 2 or 3 days rather than
      1 day.

PMID- 9640186
TI  - Efficacy of probing as treatment of epiphora in adults with blocked nasolacrimal
      ducts.
AB  - AIMS: To determine the efficacy of probing in the initial treatment of epiphora
      and the symptom free period in adults with blocked nasolacrimal ducts. METHODS:
      The results of probing in 85 eyes with epiphora due to nasolacrimal duct
      obstruction were studied retrospectively after a mean follow up of 7.4 months (SD
      11.6) by a questionnaire and interview survey of patients. RESULTS: 35% of the
      eyes had an outcome of no watering after probing, 17% mild watering, 35% moderate
      watering, and 11% severe watering. The patients' satisfaction (watering
      subjectively improved) after undergoing this procedure was 82%, which is higher
      than previously reported. The mean symptom free period in eyes with no watering
      was 11.25 months, in eyes with mild watering 8.20 months, in eyes with moderate
      watering 5.35 months, and in eyes with severe watering 0.95 months. There was a
      significant difference (p = 0.001) in the symptom free period between the no
      watering and severe watering groups. CONCLUSIONS: Probing in adults with
      confirmed nasolacrimal duct obstruction can be recommended as an initial
      treatment procedure because of its relatively good efficacy and high patient
      satisfaction without compromising subsequent surgical treatment if unsuccessful.

PMID- 9640187
TI  - Open lacrimal surgery: a comparison of admission outcome and complications after
      planned day case or inpatient management.
AB  - AIMS: To assess the outcome, in terms of completion of admission and complication
      rates, for two series of patients undergoing open lacrimal surgery, one group
      planned for a day case admission and the other planned for inpatient stay.
      METHODS: A retrospective analysis of case notes was performed for 200 patients
      planned to have day case admission (for 209 open lacrimal operations) and the
      details compared with those for 200 inpatient admissions (for 228 lacrimal
      procedures) during the same period of study. The success rates for surgery were
      not examined. RESULTS: 9% of planned day cases required overnight admission, 5.5%
      for medical reasons and 3.5% for social or administrative reasons. There was a
      similar incidence of postoperative complications in planned day cases and
      inpatients, although 6% of day case patients developed postoperative cellulitis,
      compared with 1.3% of the inpatients (p = 0.01). Overall, the incidence of
      cellulitis was greater in cases complicated by intraoperative haemorrhage (p <
      0.05) or the use of absorbable nasal packing (p < 0.0001). A similar number of
      patients in each group attended the accident and emergency department before the
      planned first postoperative clinic visit. CONCLUSION: Patients undergoing open
      lacrimal surgery can be safely managed as day cases if carefully selected for
      suitability on social and medical criteria. The use of general anaesthesia is
      not, in itself, a contraindication to day case lacrimal surgery.

PMID- 9640188
TI  - Trabeculectomy augmented with mitomycin C application under the scleral flap.
AB  - AIM: The authors investigated the safety and intraocular pressure (IOP) lowering
      effectiveness of trabeculectomy augmented with mitomycin C application beneath
      the scleral flap, and assessed the influence of preoperative risk factors on the
      surgical outcome. METHODS: A retrospective study of 72 consecutive high risk eyes
      undergoing trabeculectomy with adjunctive mitomycin C (0.2 mg/ml) applied under
      the scleral flap for 5 minutes was performed. Each eye was ascribed a score based
      on the number of preoperative risk factors, and categorised into one of three
      risk factor groups. Success was described as unqualified where IOP was < or = 21
      mm Hg without medication and qualified where antiglaucomatous therapy was
      required to maintain it at such a level. A life table analysis of IOP control was
      calculated. RESULTS: The mean IOP (SD) fell from a preoperative level of 28.4
      (6.9) to a level of 16.63 (8.06) mm Hg at the last follow up (paired Student's t
      test: p < 0.0001). Fifty two eyes (72%) were classed as unqualified successes.
      The survival rates did not differ significantly between different risk factor
      groups (log rank test: chi 2 = 0.967, p > 0.1). The incidence of postoperative
      complications compared favourably with reports of mitomycin C application between
      Tenon's capsule and the undissected scleral bed. CONCLUSION: The results
      illustrate that mitomycin C applied beneath the scleral flap during
      trabeculectomy in high risk eyes is associated with a success rate comparable to
      other modes of application. The incidence of potentially serious complications
      such as conjunctival wound leak and prolonged hypotony was lower than previously
      published data reporting sub-Tenon's administration of mitomycin C. The number
      and nature of preoperative risk factors do not appear to influence the surgical
      outcome. A possible mechanism of action is proposed.

PMID- 9640189
TI  - Effects of latanoprost and dipivefrin, alone or combined, on intraocular pressure
      and on blood-aqueous barrier permeability.
AB  - AIM: To investigate the effect on intraocular pressure (IOP) and aqueous flare of
      topical applications of latanoprost and dipivefrin alone or combined. METHODS: 22
      patients with open angle glaucoma or ocular hypertension were included in a 4
      week open label study. Median age was 68 years (range 50-79). They were allocated
      to either 2 weeks' treatment with once daily evening administration of
      latanoprost monotherapy (50 micrograms/ml) or twice daily dipivefrin monotherapy
      (1 mg/ml), followed by 2 weeks' combination therapy with both drugs. RESULTS:
      Latanoprost alone reduced IOP from 19.3 (SD 1.4) to 14.8 (0.9) mm Hg (p < 0.01).
      Addition of dipivefrin caused a further reduction to 12.4 (0.9) mm Hg (p < 0.01
      compared with latanoprost alone). In the group where the treatment started with
      dipivefrin IOP was reduced from 22.3 (1.2) to 18.4 (1.0) mm Hg (p < 0.01) and
      with the combination to 14.9 (0.9) mm Hg (p < 0.01). No change in aqueous flare
      was observed with either drug, alone or in combination. A slight increase in
      conjunctival hyperaemia was observed when the two drugs were combined.
      CONCLUSIONS: Latanoprost and dipivefrin have an additive effect on IOP and no
      clinically significant effect on the permeability to proteins of the blood
      aqueous barrier. This implies that the two drugs can be a useful combination for
      the treatment of glaucoma.

PMID- 9640190
TI  - Diabetic retinopathy in Down's syndrome.
AB  - AIM: To determine the prevalence of diabetic retinopathy in patients with Down's
      syndrome and diabetes mellitus. METHODS: Nine patients with Down's syndrome and
      diabetes mellitus were assessed. Factors recorded included type and duration of
      diabetes, level of diabetic control, blood pressure, urinalysis, and results of
      ophthalmological examination. RESULTS: The duration of diabetes ranged from 8 to
      41 years (mean 17.6 years). All had satisfactory glycaemic control and blood
      pressure measurements on the low side of normal (mean 106.6/70 mm Hg). One
      patient had early background diabetic retinopathy. The remainder had no evidence
      of diabetic retinopathy. CONCLUSION: The low prevalence of diabetic retinopathy
      in these Down's syndrome patients, despite the long duration, is an interesting
      finding. It suggests some inherent protective factor against the development of
      diabetic retinopathy in this patient subgroup.

PMID- 9640191
TI  - Use of eye care services by people with diabetes: the Melbourne Visual Impairment
      Project.
AB  - AIM: The use of eye care services by people with and without diabetes was
      investigated in the Melbourne Visual Impairment Project (VIP), a population based
      study of eye disease in a representative sample of Melbourne residents 40 years
      of age and older. METHODS: A comprehensive interview was employed to elicit
      information on history of diabetes, medication use, most recent visit to an
      ophthalmologist and optometrist, and basic demographic details. Presence and
      extent of diabetic retinopathy was determined by dilated fundus examination.
      RESULTS: The Melbourne VIP comprised 3271 people who ranged in age from 40 to 98
      years; 46.2% of them were male. Of 3189 people who had the fundus examination and
      knew their diabetes status, 162 (5.1%) reported having been previously diagnosed
      with diabetes and, of these, 37 (22.2%) were found to have diabetic retinopathy.
      Seven people (4.3%) had developed diabetes before age 30. The mean duration of
      diabetes was 9.2 years. People with diabetes were significantly more likely to
      have visited an ophthalmologist ever or in the past 2 years than people without
      diabetes. However, 31.8% of people with diabetes had never visited an
      ophthalmologist. The proportion of people who had never seen an ophthalmologist
      was 47.1% for people without diabetes, 34.2% for people with diabetes but without
      diabetic retinopathy, and 25% for people with diabetic retinopathy. Sixty one per
      cent of people with diabetic retinopathy had seen an ophthalmologist in the past
      year and a further 3% within the past 2 years. People with diabetes were not
      significantly more likely to have visited an optometrist than people without
      diabetes (p = 0.51). Overall, 37.7% of people with diabetes and 32.9% of people
      without diabetes had visited an optometrist within the past year (chi 2 = 2.25, 1
      df, p = 0.13). Information concerning retinal examinations was available for 135
      individuals (83.3% of people with diabetes). Only 74 (54.8%) could recall ever
      having a dilated fundus examination; 10 (14%) by an optometrist, 62 (86%) by an
      ophthalmologist, and five (7%) by a general practitioner. Of those 68 people who
      had seen an ophthalmologist in the past 2 years, 48 (71%) reported a dilated
      fundus examination during that time. This compares with 28 (43%) reported dilated
      fundus examinations in the 65 people who had seen an optometrist in the past 2
      years. This finding is statistically significant (chi 2 = 10.2, 1 df, p < 0.005).
      CONCLUSION: These results indicate that nearly half of people with diabetes in
      Melbourne are not receiving adequate screening or follow up for diabetic
      retinopathy, despite universal health care.

PMID- 9640192
TI  - A new computer program for mass screening of visual defects in preschool
      children.
AB  - AIMS: To test the effectiveness of a PC computer program for detecting vision
      disorders which could be used by non-trained personnel, and to determine the
      prevalence of visual impairment in a sample population of preschool children in
      the city of Beer-Sheba, Israel. METHODS: 292 preschool children, aged 4-6 years,
      were examined in the kindergarten setting, using the computer system and "gold
      standard" tests. Visual acuity and stereopsis were tested and compared using
      Snellen type symbol charts and random dot stereograms respectively. The
      sensitivity, specificity, positive predictive value, negative predictive value,
      and kappa test were evaluated. A computer pseudo Worth four dot test was also
      performed but could not be compared with the standard Worth four dot test owing
      to the inability of many children to count. RESULTS: Agreement between computer
      and gold standard tests was 83% and 97.3% for visual acuity and stereopsis
      respectively. The sensitivity of the computer stereogram was only 50%, but it had
      a specificity of 98.9%, whereas the sensitivity and specificity of the visual
      acuity test were 81.5% and 83% respectively. The positive predictive value of
      both tests was about 63%. 27.7% of children tested had a visual acuity of 6/12 or
      less and stereopsis was absent in 28% using standard tests. Impairment of fusion
      was found in 5% of children using the computer pseudo Worth four dot test.
      CONCLUSIONS: The computer program was found to be stimulating, rapid, and easy to
      perform. The wide availability of computers in schools and at home allow it to be
      used as an additional screening tool by non-trained personnel, such as teachers
      and parents, but it is not a replacement for standard testing.

PMID- 9640193
TI  - Comparison of decentration and tilt between one piece and three piece polymethyl
      methacrylate intraocular lenses.
AB  - BACKGROUND: The extent of the decentration and tilt was prospectively compared
      between one piece polymethyl methacrylate (PMMA) and three piece PMMA intraocular
      lenses (IOLs) which were implanted in the capsular bag after performing
      continuous curvilinear capsulorhexis. METHODS: 91 patients underwent a one piece
      PMMA IOL implantation in one eye as well as the implantation of the three piece
      PMMA IOL with polyvinylidene fluoride loops in the opposite eye. The length of
      the lens decentration and the angle of the tilt were quantitated using the
      anterior eye segment analysis system (EAS-1000) at 1 week as well as 1, 3, and 6
      months postoperatively. RESULTS: The mean length of the decentration in the one
      piece IOL was smaller than that in the three piece IOL at 1 week (p = 0.0092), 1
      month (p = 0.0044), 3 months (p = 0.0069), and 6 months (p = 0.0010)
      postoperatively. However, no significant difference was found in the degree of
      the tilt between the two types of IOLs throughout the observation periods.
      CONCLUSION: These results clarified that the one piece PMMA IOL with rigid PMMA
      haptics implanted in the capsular bag provides a better centration than the three
      piece PMMA IOL with flexible haptics, whereas the tilt was the same between the
      two types of IOLs.

PMID- 9640194
TI  - Ocular complications of heart, lung, and liver transplantation.
AB  - AIM: To document the nature and frequency of ocular complications in a large
      group of patients who underwent heart, lung, or liver transplantation. METHODS: A
      retrospective audit of the medical records of all patients undergoing heart,
      lung, or combined heart-lung transplantation at St Vincent's Hospital, Sydney, or
      liver transplantation at Royal Prince Alfred Hospital Sydney, was performed to
      detect patients with symptomatic ocular complications following transplantation.
      19 of 860 patients were identified as having ocular complications. RESULTS:
      Ocular complications occurred in 2% of patients with 65% of these being
      opportunistic infections. Herpes group viral retinitis (77%) and fungal
      chorioretinitis (22%) were seen. Other complications included choroidal
      pseudolymphoma, central retinal vein occlusion, herpes zoster ophthalmicus,
      herpetic keratitis, dacryocystitis, cyclosporin retinopathy, and rifabutin
      associated uveitis. CONCLUSION: Herpes group viral retinitis was the most common
      ocular opportunistic infection and occurred most frequently during the second
      year after transplantation. Delayed diagnosis was associated with poor visual
      outcome.

PMID- 9640195
TI  - Use of indomethacin for pain relief following scleral buckling surgery.
AB  - BACKGROUND/AIMS: Patients undergoing scleral buckling and cryotherapy suffer from
      mild to moderate postoperative pain. As good pain relief facilitates post
      operative ocular examination, as well as patient comfort and recovery, the
      authors designed a prospective randomised double masked trial to evaluate the
      efficacy of indomethacin as a satisfactory analgesic for such patients. METHOD:
      Patients with a primary uncomplicated rhegmatogenous retinal detachment requiring
      scleral buckling and cryotherapy were randomly allocated to receive either
      indomethacin or placebo. A rectal suppository was administered 2 hours before
      surgery, followed by two capsules twice daily for 10 days. Pain relief was
      assessed with a linear graphic rating scale at the end of each day. Supplementary
      analgesia was allowed and recorded. RESULTS: 12 patients received indomethacin
      (group A) and 16 received placebo (group B). The extent of surgery was similar in
      both groups. One patient in group A, and two in group B withdrew after 3 days.
      The pain scores were converted to changes from the baseline (score on day 1), and
      the area under the curve calculated for each patient. The means of the areas were
      analysed with the Mann-Whitney test and showed that indomethacin caused a
      statistically significant reduction in pain score, both at 3 days (p = 0.04) and
      at 10 days (p = 0.014). There was no statistically significant difference in
      extra analgesic requirements between the two groups (p = 0.2). CONCLUSIONS:
      Indomethacin is recommended for short to medium term pain relief following
      scleral buckling and cryotherapy.

PMID- 9640197
TI  - Vitreous intercellular adhesion molecule 1 in uveitis complicated by retinal
      detachment.
AB  - AIMS: The vitreous levels of soluble intercellular adhesion molecule 1 (sICAM-1)
      were investigated in uveitic eyes undergoing vitrectomy for retinal detachment
      (RD) or other complications, and the presence of this molecule was related to
      disease activity and vitreous levels of the cytokine tumour necrosis factor alpha
      (TNF alpha), known to upregulate ICAM-1 expression on various cells. METHODS:
      Vitreous and serum samples from 23 patients with either active or quiescent
      uveitis undergoing retinal surgery were examined for the levels of immunoreactive
      sICAM-1 and TNF alpha by ELISA methods, and for the presence of biologically
      active TNF alpha. Vitreous from non-uveitic eyes with rhegmatogenous retinal
      detachment (RRD), macular holes or cadaveric eyes were used as controls. RESULTS:
      As a whole, vitreous from uveitic eyes complicated or uncomplicated by RRD
      contained significantly higher levels of sICAM-1 than vitreous from non-uveitic
      eyes with RRD alone (p < 0.0005), eyes with macular holes (p < 0.0001), or normal
      cadaveric vitreous (p < 0.0001). The proportion of vitreous containing > 20 ng/ml
      sICAM-1 (> four times the normal values) was significantly higher in eyes with
      uveitis complicated by RRD than in those eyes without RRD (Fisher's test, p =
      0.02), and although levels of sICAM-1 were higher in eyes with active uveitis
      than in those with quiet disease (p < 0.02), this could not be dissociated from
      the increase caused by RRD. There was a relation between the vitreous levels of
      sICAM-1 and those of immunoreactive TNF alpha (Spearman's correlation
      coefficient; r = 0.601, p = 0.006), but not between the vitreous levels of sICAM
      1 and those of biologically active TNF alpha. CONCLUSION: Increased vitreous
      sICAM-1 levels and the association of this molecule with the presence of
      immunoreactive TNF alpha in uveitic eyes confirm the operation of cytokine
      mediated vascular reactions at the blood-retinal barrier during the development
      of this condition. The persistence of high vitreous levels of sICAM-1 in eyes
      with uveitis complicated by RRD despite previous immunosuppression may indicate a
      low rate of clearance of inflammatory molecules from the vitreous cavity and an
      exacerbation of the existing inflammatory process by the retinal detachment
      itself.

PMID- 9640196
TI  - Adhesion molecules in iris biopsy specimens from patients with uveitis.
AB  - BACKGROUND/AIMS: Earlier studies on intraocular tissue have demonstrated that T
      lymphocytes play a major role in the pathogenesis of uveitis. Adhesion molecules
      are immunoregulatory molecules for the interaction between T lymphocytes and
      vascular endothelium and they play an important role in the recruitment of
      specific T lymphocytes from the circulation into inflamed tissue. In uveitis an
      increased expression of some of these adhesion molecules may be expected.
      METHODS: The presence of adhesion molecules was investigated in iris biopsy
      specimens from 11 patients with uveitis and eight controls (patients with primary
      open angle glaucoma) immunohistochemically with a panel of monoclonal antibodies:
      LECAM (CD 62L), ICAM-1 (CD 54), LFA-1 (CD 11a/18), VCAM-1 (CD 106), VLA-4 (CD
      49d), and HECA-452, a marker for high endothelial venules. RESULTS: Positive
      staining for ICAM-1, LFA-1 and VCAM-1 was found in the iris in a significantly
      higher number of uveitis patients than in controls. The remaining adhesion
      molecules were also found in a higher number of uveitis patients than in
      controls, but this difference did not reach statistical significance. CONCLUSION:
      An increased expression of adhesion molecules was found in the iris of patients
      with uveitis, indicating an immunoregulatory function for adhesion molecules in
      the pathogenesis of uveitis.

PMID- 9640198
TI  - Quantitative analysis of lipid deposits from Schnyder's corneal dystrophy.
AB  - AIM: To report the quantitation of the lipid composition of a corneal button from
      a Japanese woman in her 60s with clinically and histopathologically proved
      Schnyder's corneal dystrophy. METHODS: Total lipids extracted from the corneal
      button of the patient were analysed by the method of thin layer chromatography
      flame ionisation detection. Two different solvent systems were used for neutral
      lipid analysis and phospholipid analysis. Results were compared with three age
      matched corneal buttons obtained from cadaveric eyes. RESULTS: The lipids that
      accumulated in the cornea in Schnyder's dystrophy consisted mainly of
      unesterified cholesterol and phospholipids. The analysis of phospholipids showed
      sphingomyelin to be the predominant phospholipid in the patient's cornea.
      CONCLUSION: Findings suggest that this disorder involves a disturbance of the
      metabolism of cholesterol and/or sphingomyelin metabolism that is limited to the
      cornea.

PMID- 9640199
TI  - Long term growth arrest of human Tenon's fibroblasts following single
      applications of beta radiation.
AB  - AIMS/BACKGROUND: Antimetabolites are increasingly used to manipulate the healing
      response after filtration surgery, but problems with thin cystic blebs have been
      encountered with the liquid agents commonly used such as 5-fluorouracil and
      mitomycin C. beta Radiation appears to be a useful adjuvant treatment for
      preventing scarring after trabeculectomy, resulting in diffuse rather than cystic
      bleb formation, but much of the basic cell biology of the ocular fibroblast
      response to beta radiation remains unclear. The effects of beta radiation on
      ocular fibroblast proliferation and cell cycling were investigated to determine
      the nature and duration of these effects on these cells. METHODS: In vitro cell
      culture techniques were used to investigate fibroblast proliferation. Cell
      viability was studied using trypan blue dye exclusion. The effect of radiation on
      cell cycling was investigated using bromodeoxyuridine uptake. p53 expression was
      demonstrated using immunocytochemistry. RESULTS: beta Radiation inhibited
      fibroblast proliferation in a dose dependent manner. Early cell death was not a
      prominent feature, but irradiated fibroblasts demonstrated a rapid onset and
      sustained period of growth arrest. p53 expression was found to be increased in
      irradiated cells. CONCLUSIONS: Single doses of beta radiation significantly
      inhibit Tenon's capsule fibroblast proliferation in vitro over a 28 day period.
      This inhibition is the result of a rapid onset and sustained period of growth
      arrest in irradiated cells. Irradiated fibroblasts show an increase in p53
      expression, a nuclear phosphoprotein which has been associated with control of
      the cell cycle. Single applications of beta radiation may be an effective
      treatment for the prevention of bleb failure as a result of prolonged growth
      arrest of Tenon's capsule fibroblasts.

PMID- 9640200
TI  - Tear lipocalin and the eye's front line of defence.

PMID- 9640201
TI  - Cystoid macular oedema in patients with AIDS and cytomegalovirus retinitis on
      highly active antiretroviral therapy.

PMID- 9640202
TI  - Aicardi syndrome.

PMID- 9640203
TI  - Paucity of signs in X linked ocular albinism with a 700 kb deletion spanning the
      OA1 gene.

PMID- 9640204
TI  - Intracranial plasmacytoma masquerading as Gradenigo's syndrome.

PMID- 9640205
TI  - Use of ultrasound biomicroscopy in the localisation and management of an
      anteriorly situated intraocular foreign body.

PMID- 9640206
TI  - Intravitreal phaco chopper fragment missed by computed tomography.

PMID- 9640207
TI  - Absence of relative afferent pupillary defect and pupillary hemiakinesia in a
      child with homonymous hemianopia due to ((retro-)geniculate) porencephaly.

PMID- 9640208
TI  - Expression of transforming growth factor beta superfamily and their receptors in
      the corneal stromal wound healing process after excimer laser keratectomy.

PMID- 9640209
TI  - Quality of life and breast cancer--the learning curve never ends.

PMID- 9640210
TI  - Should cancer patients with incurable disease receive parenteral or enteral
      nutritional support?

PMID- 9640211
TI  - Irinotecan and 5-fluorouracil in colorectal cancer: time for a pause?

PMID- 9640212
TI  - Electronic biomedical journals: how they appear and what they offer.
AB  - This study, prompted by a number of articles presaging the imminent demise of
      biomedical journals due to the rise of their electronic spread, analysed 54 Web
      sites of the journals included in the Oncology section of the Science Citation
      Index, Journal Citation Reports (1994) and the sites of 10 other leading
      digitised biomedical journals. The aim was to determine quantitative and
      qualitative differences in terms of information content existing between the two
      media. The analysis confirmed that there are limits to the information contained
      in the scientific journals currently on the Internet and upholds the authors'
      conclusion that, in the oncology field, the printed journal will continue to have
      an important role for most individual users for some time.

PMID- 9640213
TI  - Comparison of 5-fluoro-2'-deoxyuridine with 5-fluorouracil and their role in the
      treatment of colorectal cancer.
AB  - Despite more than 30 years of intensive studies on new drugs against advanced
      colorectal cancer, the fluoropyrimidines remain the drugs of choice for systemic
      treatment and for hepatic artery infusion (HAI). This overview describes new
      developments in advanced colorectal cancer chemotherapy, providing a rationale
      for more effective use of the fluoropyrimidines, with biochemical modulation,
      scheduling or by revealing biochemical mechanisms of action that correlate with
      antitumour activity. In human colorectal cancer cell lines and various animal
      tumour model systems 5-fluoro-2'-deoxyuridine (FdUrd) is more effective than 5
      fluorouracil (5-FU). Comparably, FdUrd's modulation by leucovorin (LV) is more
      potent than 5-FU. In animal studies it is shown that intermittent high-bolus
      administration of FdUrd generates better antitumour activity, compared with equal
      toxic doses or any other schedule of 5-FU. These effects are related to prolonged
      thymidylate synthase (TS) inhibition and the prevention of TS induction, rather
      than RNA incorporation. Preclinical studies with modulators such as N
      phosphonacetyl-L-aspartate (PALA), WR-2721, mitomycin C and platinum derivatives
      provide a rationale for clinical use in the future. The first choice systemic
      chemotherapy of patients with advanced colorectal cancer remains 5-FU combined
      with LV. Some improvement in therapeutic efficacy has been achieved with
      locoregional HAI. In randomised studies HAI FdUrd improves the quality of life
      and survival as compared with optimal systemic therapy. Chronomodulation
      decreases toxicity, allowing dose intensification, while modulators such as LV or
      dexamethasone increase survival of patients treated with HAI FdUrd to 86% after 1
      year. In conclusion, the clinical use of FdUrd has not been fully explored.
      Intermittent high-dose FdUrd, chronomodulation together with the use of
      modulators or drugs focused on prolonged TS inhibition, should be studied in
      large randomised studies.

PMID- 9640214
TI  - Quality of life of early-stage breast cancer patients treated with radical
      mastectomy or breast-conserving procedures: results of EORTC Trial 10801. The
      European Organization for Research and Treatment of Cancer (EORTC), Breast Cancer
      Co-operative Group (BCCG).
AB  - In 1980 the EORTC-BCCG initiated a multicentre randomised clinical trial
      comparing modified radical mastectomy (MRM) with breast-conserving therapy (BCT)
      in stage I and II breast cancer. The main endpoint of the trial was survival. A
      brief quality of life (QoL) questionnaire consisting of two multi-item scales
      (body image and fear of recurrence) and two single items (satisfaction with
      treatment and cosmetic result) was included in the trial. A cosmetic evaluation
      of the breast after conservative surgery was also performed. This report
      concentrates on the results of the QoL study and the cosmetic evaluation.
      Multitrait scaling analysis was employed to verify the hypothesised scale
      structure of the questionnaire. Treatment comparison of the QoL scores at 2 years
      post-treatment was performed using a stratified Wilcoxon rank sum test. Both
      patients' and doctors' ratings of the cosmetic result were documented on the
      clinical follow-up form. A multivariate analysis was performed to identify which
      factors influenced the cosmetic outcome. In total, 127 patients in the MRM arm
      and 151 in the BCT arm completed a QoL questionnaire at approximately 2 years
      after randomisation (months 25-36). The Cronbach's alpha coefficients were 0.79
      and 0.73 for the body image and fear of recurrence scales, respectively.
      Significant benefit in body image and satisfaction with treatment was observed in
      the BCT patients. No significant difference was observed in fear of recurrence
      between the two groups. Ratings of cosmetic results decreased with time, in line
      with clinical observations of long-term side-effects of radiotherapy. Wide
      excision appeared to be the most important predictive factor for poor cosmetic
      result. In this multicentre randomised study, BCT helped to maintain the
      patients' body image, resulted in higher satisfaction with treatment and yielded
      no significant difference from MRM with respect to fear of recurrence.

PMID- 9640215
TI  - Eight-year results of a prospective non-randomised study on therapy of small
      breast cancer. The German Breast Cancer Study Group (GBSG).
AB  - In this report, the results of the first controlled clinical trial on breast
      cancer in Germany, begun in 1983, are presented after a median follow-up of 8
      years. Four-year results have been previously published. In pT1 N0 M0 breast
      cancer, mastectomy as the standard treatment was to be compared with tumorectomy
      plus radiotherapy to the remaining breast tissue. The study design, originally
      planned as a comprehensive cohort study including randomised and non-randomised
      patients, had to be changed into a prospective observation study due to the low
      randomisation rate. 1036 out of 1119 recruited patients were evaluable. After a
      median follow-up of 97 months, 237 events (local recurrence, regional recurrence,
      distant metastases, contralateral breast cancer or death of the patient without
      previous recurrence) occurred. With the exception of death without recurrence,
      the events were evenly distributed among the two treatment groups. The 8-year
      local recurrence rate of the whole patient population is 8.8%. Out of all
      prognostic factors examined, only tumour size and grade had a significant
      influence on recurrent disease. Event-free survival decreased in cases with
      'uncertain' tumour margins, whereas the width of the margin has no influence on
      disease recurrence. Based on 151 deaths observed so far, there was no significant
      difference in overall survival between the two treatment groups. The 8-year
      results of this study are in accordance with the 4-year results reported
      previously and with those of other breast-conserving treatment trials. There was
      no significant difference between the two treatment groups with regard to event
      free and overall survival. Incomplete tumorectomy had a negative influence on
      recurrence.

PMID- 9640216
TI  - The use of complementary therapies by breast cancer patients attending
      conventional treatment.
AB  - The aim of this study was to measure the proportion and characteristics of
      complementary therapy (CT) users among female breast cancer patients receiving
      conventional treatment. 473 women who had received surgical intervention for
      breast cancer in the year of diagnosis were sent a questionnaire for completion,
      and 242 responded. CT had been used by 16.5% after cancer diagnosis, only 8.7%
      before. The most commonly used CTs were homeopathy, manual healing method,
      herbalism and acupuncture. The main reason for using CTs was physical distress.
      Only a minority was searching for psychological support. 24 users were satisfied
      with these treatments, and two-thirds would suggest them. Users were
      significantly younger, more educated, and previous users of CTs than non-users.
      Adjusting each variable for the effect of the others, only previous use had an
      independent effect on increasing the probability of being users after cancer
      diagnosis.

PMID- 9640217
TI  - Mantle cell lymphoma: clinical features, treatment and prognosis of 94 patients.
AB  - Mantle cell lymphoma (MCL) is a subtype of B-cell non-Hodgkin's lymphoma recently
      recognised as a distinct disease entity. Little is known about the prognostic
      factors and optimal treatment of MCL. The aim of this study was to analyse
      retrospectively the clinical features and effect of treatment in 94 MCL patients
      diagnosed and treated in one centre between 1980 and 1996, and to find out
      different factors influencing the treatment results and prognosis. The median age
      of the patients was 66 years, and 77% were over 60 years old. Of the patients,
      76% had advanced disease, the performance status (PS) was WHO 0-1 in 86%, and B
      symptoms were present in 35% of the cases. Bone marrow infiltration was found in
      61% and overt leukaemia in 12% of the patients. Of the patients, 47% achieved
      complete remission with first- or second-line therapy. The median duration of
      remission, time to treatment failure (TTF), and survival were 28, 18, and 41
      months, respectively. In multivariate analyses, age, stage and leukaemic disease
      were significantly associated with TTF, and age, stage, leukaemic disease and
      lactate dehydrogenase (LDH) with survival. Long-term prognosis is poor in MCL.
      None of the conventional chemotherapies seems curative. A prospective randomised
      trial should be made to evaluate the benefit of anthracycline-containing regimens
      in MCL.

PMID- 9640218
TI  - Vessel counts and vascular endothelial growth factor expression in pancreatic
      adenocarcinoma.
AB  - Angiogenesis is essential for growth and metastasis of solid malignancies. In
      several tumours, tumour vessel count and expression of vascular endothelial
      growth factor (VEGF), a potent angiogenic factor, have been associated with
      prognosis. To determine if vessel count and VEGF expression are prognostic
      factors in pancreatic cancer, we examined these parameters in resected tumour
      specimens from 22 patients who did not receive pre-operative therapy. Paraffin
      embedded tumour specimens were immunohistochemically stained for factor VIII
      (surrogate for vessels) and VEGF. Vessel counts and VEGF expression were
      evaluated without knowledge of patient outcome. The median follow-up for the
      entire group had not been reached as of 23.1 months (range 10-69 months). The
      mean vessel count and VEGF expression were no different between those patients
      who had recurrences and those who did not. By linear regression analysis, the
      correlation of VEGF expression with vessel count did not reach statistical
      significance (P = 0.0685). Survival and time to recurrence were similar in
      patients with high and low vessel counts and VEGF expression of 1, 2 or 3. Tumour
      differentiation or lymph node positivity had no effect on either VEGF expression
      or vessel count. Our data suggest that, in contrast to findings in other solid
      malignancies, vessel count and VEGF expression are not predictors of survival or
      recurrence in patients with resectable adenocarcinoma of the pancreas.

PMID- 9640219
TI  - Long-term survival following neoadjuvant chemotherapy and radical surgery in
      locally advanced cervical cancer.
AB  - The aim of this study was to analyse the long-term survival and the relationships
      between prognostic factors at presentation, chemoresponsiveness and disease
      outcome in patients with locally advanced cervical cancer treated by neoadjuvant
      chemotherapy and radical surgery (RS). Two consecutive studies of neoadjuvant
      chemotherapy containing cisplatin, bleomycin plus/minus methotrexate followed by
      radical hysterectomy and systematic aortic and pelvic lymphadenectomy were
      carried out between January 1986 and September 1990 on 130 patients with > or = 4
      cm stage IB2-III cervical cancer. Survival analysis was performed using the
      Kaplan and Meier test and Cox's multivariate regression analysis. 128 (98%) of
      the patients enrolled were evaluable for clinical response and survival, 83%
      (106) of the patients responded to chemotherapy, with a 15% complete response
      rate. Logistic regression analysis demonstrated that International Federation of
      Gynecology and Obstetrics (FIGO) stage, cervical tumour size, parametrial
      involvement and histotype are highly predictive of response. Responding patients
      underwent laparotomy, but 8% were not amenable for radical surgery. The 10-year
      survival estimates were 91%, 80% and 34.5% for stage IB2-IIA bulky, IIB and III,
      respectively (P < 0.001). After Cox's regression analysis, the parameters
      significantly associated with survival were the same factors predicting response
      to neoadjuvant chemotherapy. No stage IB2-IIA bulky patient has so far relapsed,
      while 12% stage IIB and 56% stage III patients recurred. The 10-year disease-free
      survival estimates are 91% and 44% for stage IB2-IIB and III, respectively (P <
      0.001). Metastatic nodes and persistent tumour in the parametria were the only
      two independent factors for disease-free survival after multiple regression
      analysis. After a long-term follow-up (median follow-up 98 months (20-129+)), our
      results give new evidence of the prognostic value of response to neoadjuvant
      chemotherapy and of a possible therapeutic benefit of the sequential treatment
      adopted which, however, must be verified in a randomised setting.

PMID- 9640220
TI  - Initial management of primary mediastinal seminoma: radiotherapy or cisplatin
      based chemotherapy?
AB  - Primary mediastinal seminoma is an uncommon neoplasm, the optimal management of
      which is still debated. Radiotherapy produces a 65% disease-free survival rate.
      We assess whether these results have been improved with the advent of cisplatin
      based chemotherapy. Data from 14 patients treated at the Institut Gustave-Roussy
      were reviewed. 9 had received cisplatin-based chemotherapy (Group 1): their
      outcome was compared with that of 5 patients treated with radiotherapy without
      chemotherapy (Group 2). We also reviewed data from the English literature using
      strict criteria, and report results concerning patients who received cisplatin
      based chemotherapy and those who received radiotherapy. 8 of the 9 patients (89%)
      in Group 1 are long-term disease-free survivors and only 3 of 5 patients in Group
      2. The patient who died in Group 1 was the only one who refused surgical
      resection of residual masses after chemotherapy. The review of the literature
      revealed that 59 of 68 (87%) patients initially managed with cisplatin- or
      carboplatin-based chemotherapy and for whom sufficient data are available, are
      long-term survivors and free of disease. Some of these patients had also received
      radiotherapy. Only 64 of 103 (62%) treated with thoracic radiotherapy without
      chemotherapy were long-term disease-free survivors. The disease-free survival
      rate of 51 patients who received cisplatin-based chemotherapy (excluding those
      who received carboplatin) was 86%. The difference in survival between patients
      administered cisplatin-based chemotherapy and those who underwent radiotherapy is
      apparently not due to unbalanced prognostic factors, the effect of time or non
      specific medical management. We conclude that cisplatin-based chemotherapy allows
      long-term disease-free survival in approximately 85% of patients. These results
      seem to be higher than those obtained without cisplatin-based chemotherapy.
      However, a randomised study is required for definitive conclusions, but it is
      very unlikely that such a study will be performed due to the rarity of this
      neoplasm. Another alternative would be a meta-analysis based on individual data.

PMID- 9640221
TI  - Cisplatin-based chemotherapy in advanced seminoma: the Institut Gustave Roussy
      experience.
AB  - The aim of this study was to report the results of cisplatin-based combination
      chemotherapy for patients with pure seminomatous tumours. 72 patients with
      advanced seminoma were treated with various cisplatin-based chemotherapy
      regimens. 61 (85%) patients achieved a sustained durable response. 11 relapses
      were observed with a median time to failure of 6 months. Overall, 60 (83%) of the
      72 patients remain alive and free of disease after a median follow-up of 64
      months. Initial clinical (age, site of primary, prior radiotherapy, extent of
      disease) and biological (serum human chorionic gonadotrophin levels, serum lactic
      dehydrogenase levels, p53 immunostaining) features which could be of predictive
      value for survival, were analysed in a univariate analysis. No variable retained
      statistical significance. High cure rates are expected after chemotherapy with
      standard cisplatin-based combinations in advanced seminoma. Renewed efforts are
      required to identify markers of chemosensitivity.

PMID- 9640222
TI  - Non-Hodgkin's lymphoma.

PMID- 9640223
TI  - Recombinant human erythropoietin in the prevention of chemotherapy-induced
      anaemia in children with malignant solid tumours.
AB  - This prospective, randomised pilot study was designed to evaluate safety,
      feasibility and efficacy of recombinant human erythropoietin (rhEPO) in the
      prevention and treatment of chemotherapy-induced anaemia in children with solid
      tumours. 20 children (age 4-18 years) undergoing cyclic combination chemotherapy
      were randomised either to a control group or to receive rhEPO at a dose of 150
      U/kg/dose subcutaneously three times/week for a minimum of 12 weeks or three
      chemotherapy cycles. Of 15 evaluable patients, 8 were randomised to the rhEPO
      group and 7 to the control group. RhEPO-treated patients showed an increase in
      the haematocrit over the first 8 weeks of therapy, with a significantly higher
      mean haematocrit at week 8 (33.2 +/- 2.1% versus 39.3 +/- 4.2% in the control and
      rhEPO groups, respectively, P < 0.05). Similarly, significantly higher
      haemoglobin concentrations could be demonstrated in the rhEPO group by week 8
      (11.06 +/- 1.35 g/dl versus 13.11 +/- 1.13 g/dl in the control and rhEPO groups,
      respectively, P < 0.05), with higher precycle haemoglobin before chemotherapy
      cycles 3 and 4 and higher midcycle haemoglobin between cycles 3 and 4. There was
      a trend towards a reduction of transfusion requirements during the 3rd month of
      therapy in rhEPO patients. The results of this pilot study indicate a significant
      benefit of rhEPO in children treated with intensive combination chemotherapy
      regimens. Further studies should target issues such as appropriate dosing, timing
      and duration of rhEPO therapy in children with cancer.

PMID- 9640224
TI  - BRCA1-positive patients are small for gestational age compared with their
      unaffected relatives.
AB  - The BRCA1 gene is thought to exert its main function early in life. We,
      therefore, studied the effects of BRCA1 mutations on birth weight and birth
      length. This was carried out by comparing 33 women with and without mutations.
      Birth weight and length were obtained from a self-administered questionnaire.
      BRCA1 mutations carriers had a significantly lower birth weight (P = 0.0041)
      compared with non-carriers, after adjustment for gestational age. They were also
      significantly shorter at birth compared with their unaffected relatives (P =
      0.0060), after adjustment for gestational age. The BRCA1 gene thus seems to
      influence the carriers in utero. The findings could imply that humans
      heterozygotic for the BRCA1 mutations may be influenced by the mutations during
      development in utero.

PMID- 9640225
TI  - Survival of breast cancer patients in Lithuania and Norway, 1988-1992.
AB  - In Norway, the incidence of breast cancer is almost twice that in Lithuania,
      whereas the mortality rates of the disease are approximately the same in both
      countries. The aim of the present study was to compare the survival of breast
      cancer patients in the two countries according to stage. The material from both
      countries included cases diagnosed between 1988 and 1992 with complete follow-up
      of date of death to the end of 1995. The Norwegian data consisted of all 9403 new
      cases recorded by the Norwegian Cancer Registry. The Lithuanian data included in
      all 1649 new cases treated at the Oncology Centre in Vilnius, which represents
      40% of breast cancer cases in Lithuania--these cases had the same distribution of
      the disease by age and stage as for the whole country. The overall 5-year
      relative survival was lower in Lithuania (57.3%) than in Norway (78.4%). Lower
      survival was observed in Lithuania compared with Norway for all stages. In stage
      I, the difference was 7.8% in absolute terms which could be explained by a higher
      proportion of small tumours among the Norwegian cancer cases (63.7% of tumours
      were 2 cm or less, while in Lithuania the proportion of small stage I tumours was
      only 27.9%). Therefore, early diagnosis within the stage I category seems
      relevant. The difference in survival was, however, most pronounced in stage II
      (20%) and III (29%). In Norway, the better overall survival is partly explained
      by a more favourable stage distribution. The lower survival of Lithuanian cases
      within stage categories could be explained by more advanced metastases to
      regional lymph nodes and by higher proportions of large tumours within stage.

PMID- 9640226
TI  - No predictive value of the micronucleus assay for patients with severe acute
      reaction of normal tissue after radiotherapy.
AB  - In approximately 5% of cancer patients undergoing radiotherapy, this treatment
      has to be interrupted because of an acute reaction of normal tissues. To test the
      possibility of predicting this type of reaction, the micronucleus assay was used
      to determine radiosensitivities of peripheral blood lymphocytes of 15 patients
      with severe acute reaction of normal tissue, 15 patients without this reaction
      and 15 healthy donors. Whole-blood cultures were irradiated with X-rays (4 Gy,
      1.08 Gy/min) and treated with cytochalasin B. The micronuclei scores observed in
      irradiated cells were corrected for the scores in unirradiated cells. Intra
      individual and interindividual variations in micronuclei scores were analysed in
      samples from healthy donors, and highly significant interindividual differences
      were found (P < 0.001). Scores of cells not irradiated in vitro were higher for
      cancer patients before radiotherapy than for healthy donors (P < 0.001), and
      those for cancer patients after radiotherapy were higher than for patients before
      radiotherapy (P < 0.001). Average micronuclei scores induced by in vitro
      irradiation were significantly higher in samples from cancer patients compared
      with those from healthy donors (P < 0.01). Moreover, all subgroups of cancer
      patients included individuals with very high levels of micronuclei after in vitro
      irradiation. There was, however, no relationship between the micronuclei scores
      and the occurrence of severe acute reactions in normal tissues.

PMID- 9640227
TI  - Antitumour activity and schedule dependency of 8-chloroadenosine-3',5'
      monophosphate (8-ClcAMP) against human tumour xenografts.
AB  - 8-Chloroadenosine-3',5'-monophosphate (8-ClcAMP) is a novel antitumour agent
      currently undergoing phase I clinical trials in several European centres. In this
      study, its antitumour activity against human tumour xenografts and its dependence
      on schedule were investigated. When administered by continuous infusion at doses
      of 100 or 50 mg/kg/day to nude mice bearing human tumour xenografts, 8-ClcAMP
      inhibited the growth of the HT 29 colorectal, ZR-75-1 breast, HOX 60 and PE04
      ovarian and PANC-1 pancreatic carcinoma xenografts. However, these infusion
      schedules produced hypercalcaemia and severe weight loss. In an attempt to
      optimise antitumour activity and minimise toxicity, several other schedules were
      studied. In comparison with continuous administration of 8-ClcAMP at 50 mg/kg/day
      for 14 days which, although producing complete growth inhibition in the HOX 60
      model, was associated with a marked body weight loss, schedules in which the
      infusion was interrupted (infusion on either days 0-4; 7-11 or days 0-2; 6-8)
      produced minimal weight loss but also reduced antitumour activity. However, co
      administration of salmon calcitonin with continuous infusion of 8-ClcAMP
      prevented both hypercalcaemia and body weight loss in 3/6 animals while still
      producing marked inhibition of tumour growth. These data indicate that 8-ClcAMP
      has broad-spectrum antitumour activity and the major side-effect of
      hypercalcaemia may at least in part be ameliorated by the use of salmon
      calcitonin.

PMID- 9640228
TI  - 3,3',4,4'-tetrachlorobiphenyl (TCB) can enhance DMBA-induced mammary
      carcinogenesis in the rat.
AB  - Polychlorinated biphenyls (PCBs) are fat-soluble environmental pollutants which
      can be stored in the fatty tissue of breast and secreted in milk. Previous
      studies have shown that PCBs can influence liver carcinogenesis in animal models
      but no such studies have been reported in breast. These experiments aimed to
      determine whether a PCB congener could influence mammary carcinogenesis using the
      rat DMBA-induced mammary tumour model system. 3,3',4,4'-Tetrachlorobiphenyl (TCB)
      enhanced the development of DMBA-induced mammary tumours in young female rats and
      did so in animals fed either a low-fat (5% w/w corn oil) or a high-fat (20% w/w
      corn oil) diet. The combination of TCB and high-fat diet resulted in tumours
      growing so fast that the experiment had to be terminated at 10.5 weeks for humane
      reasons. At termination the total numbers of tumours in each group of 20 rats
      were: 4 in the low-fat group, 22 in the low-fat plus TCB group, 25 in the high
      fat group and 50 in the high-fat plus TCB group. Histopathological analysis
      confirmed that 98% of the tumours were mammary carcinomas, predominantly in situ
      ductal carcinomas, but, in addition, revealed that 13 of the tumours had an
      invasive phenotype of which 12/13 had all arisen in TCB-treated animals. This
      demonstrates, for the first time, that a PCB congener can influence mammary
      carcinogenesis.

PMID- 9640229
TI  - Serum levels of intercellular adhesion molecule 1 (ICAM-1) in patients with
      colorectal cancer: inhibitory effect on cytotoxicity.
AB  - A positive correlation between the level of ICAM-1 in serum and the stage of
      neoplastic processes has been demonstrated. We studied ICAM-1 serum concentration
      in 27 colorectal cancer patients and investigated the effect of this molecule on
      cellular aggregation and toxicity. ICAM-1 serum concentration in the group of
      patients was significantly higher (P < 0.01) than in normal controls and was
      related to tumour stage. Patient sera inhibited both the formation of cellular
      aggregates and the percentage of specific lysis, the effect being lost when the
      serum was depleted of ICAM-1. These results suggest that the release of soluble
      ICAM-1 may represent a mechanism of tumour escape.

PMID- 9640230
TI  - Dipeptidyl peptidase III in malignant and non-malignant gynaecological tissue.
AB  - Exopeptidases, in contrast to endopeptidases (proteinases) have been much less
      studied in relation to cancer. The aim of this study was to investigate one such
      enzyme, dipeptidyl peptidase III (DPP III), in gynaecological tissues, by
      measuring both the enzyme activity and enzyme content. DPP III activity was
      assessed in normal (n = 65), benign (n = 9) and malignant (n = 51) gynaecological
      tissues. A statistically significant higher DPP III activity was observed in
      endometrial (n = 40, P = 4.6 x 10(-7)) and ovarian (n = 11, P = 8.1 x 10(-4))
      malignant tumours, whereas no significant difference was detected for leiomyomas
      (n = 8), if compared to the activity in normal tissue. A matched pair analysis of
      normal and cancerous endometrial tissue confirmed the significance of the DPP III
      activity increase in the transformed tissue (n = 7, P = 0.022). Western blot
      analysis revealed a significantly (P = 0.014) increased level of DPP III in
      endometrial cancer. Further, regression analysis showed a positive correlation
      between the activity and the content of DPP III in normal tissue (r = 0.637, P =
      0.047) and in endometrial cancer (r = 0.574, P < 0.007). The increase of the DPP
      III activity was observed in the endometrial carcinomas of various histological
      types, grade or the depth of myometrial invasion. The easy-to-perform
      determination of this exopeptidase activity may serve as a potential indicator of
      endometrial and ovarian malignancies.

PMID- 9640231
TI  - Potentiated antitumour effects of cisplatin and lovastatin against MmB16 melanoma
      in mice.
AB  - Lovastatin, the drug used in the treatment of hypercholesterolaemia, has
      previously been reported to exert synergistic antitumour activity in a melanoma
      model in mice when used together with some immune response modifiers. In this
      study, we examined the antitumour effect of cisplatin augmented by its combined
      application with lovastatin, both in vitro and in vivo, in a murine melanoma
      model. The results of this study suggest that lovastatin may enhance the
      therapeutic effects of cisplatin in the treatment of malignant melanomas.

PMID- 9640232
TI  - Pharmacokinetics of cisplatin with and without amifostine in tumour-bearing nude
      mice.
AB  - Amifostine (Ethyol, WR-2721) is in use in the clinic as a protector against
      platinum-induced toxicities. We have previously reported that amifostine induced
      a potentiation of the antitumour activity of carboplatin in human ovarian cancer
      xenografts. An influence of amifostine on the pharmacokinetics of carboplatin,
      resulting in higher platinum concentrations in plasma and tissues of the tumour
      bearing nude mice, was thought to be the cause of enhancement of the antitumour
      activity. Therefore, the pharmacokinetics of cisplatin were investigated in
      tumour-bearing nude mice treated with cisplatin alone or in combination with
      amifostine. A significant increase in the area under the curve (AUC) of the total
      platinum concentration in mice treated with amifostine was only observed in the
      kidney (from 355 to 398 nmol h/g), whereas in the other tissues and plasma no
      significant changes were measured. The selective protection of normal tissues by
      amifostine was confirmed by a decrease in the AUC of the cisplatin-DNA adduct
      levels in normal tissues. The decrease was only significant in the liver (282-240
      fmol h/microgram DNA), whereas in tumour tissue a slight increase in the AUC of
      the cisplatin-DNA adducts could be detected (91.3-110.1 fmol h/microgram DNA).
      The minor influence of amifostine on the pharmacokinetics of cisplatin may be the
      reason why amifostine did not potentiate the antitumour activity of cisplatin.
      The influence of amifostine on cisplatin-DNA adduct levels in normal tissues
      versus tumour tissues is further evidence for the usefulness of this toxicity
      modulator in cancer patients.

PMID- 9640233
TI  - Identification of a new commonly deleted region within a 2-cM interval of
      chromosome 11p11 in breast cancers.
AB  - Allelic loss has been observed on the short arm of chromosome 11 in a variety of
      human cancers. We have examined 184 breast cancers for allelic loss anywhere in
      chromosome 11p, using 15 well-spaced microsatellite markers. Allelic loss was
      observed in 86 cases (47%) and a new commonly deleted region 2-cM in length was
      identified at 11p11 between loci D11S986 and D11S1313, in addition to a 12-cM
      region of a common deletion at 11p15.5. A significant association was found
      between allelic loss on 11p15.5 and LOH on 11p11 and the loss of progesterone
      receptors.

PMID- 9640234
TI  - Results of a phase II trial with second-line cystemustine at 60 mg/m2 in advanced
      soft tissue sarcoma: a trial of the EORTC Early Clinical Studies Group.
AB  - The aim of this phase II trial was to examine the efficacy of a new nitrosourea,
      cystemustine, in soft tissue sarcoma. Between January 1990 and March 1991, 32
      pretreated patients with advanced soft tissue sarcoma were enrolled. Cystemustine
      was given every 2 weeks at 60 mg/m2 via a 15-min i.v. infusion. All eligible
      patients were considered evaluable for response and toxicity (WHO criteria). Of
      the 32 enrolled patients, 4 were ineligible, leaving 28 evaluable patients. All
      but 1 had been pretreated: 6 with adjuvant chemotherapy, 18 patients with first
      line palliative chemotherapy without nitrosourea, 3 with both treatments, and 18
      had received radiotherapy. Median age was 54 years (range 20-73) and median
      performance status was 1 (0-2). One partial response (PR, duration 12 weeks), 2
      stable disease and 25 progressions were observed, giving an overall response rate
      of 3.57% (confidence interval: 0.1-18.4%). Toxicity was mild, and was mainly
      neutropenia (no grade 3 or 4), thrombocytopenia (3.57% grade 3 and grade 4) and
      nausea-vomiting (no grade 3 or 4). It should be noted that the treatment for the
      patient who obtained a PR was third line with no previous response. Cystemustine
      with this schedule appears to have a low clinical activity and toxicity in
      advanced soft tissue sarcoma.

PMID- 9640235
TI  - alpha-Melanotropin immunoreactivity in human melanoma exudate is related to
      necrosis.
AB  - We have previously reported high immunoreactive alpha-MSH (IR-alpha-MSH)
      concentrations in melanoma patients' plasma, as well as significant amounts in
      melanoma metastases and cells grown in culture. Necrosis within the melanoma
      tumour leads to a massive proteolysis of intracellular proteins and release of
      cell content: this might significantly contribute to the elevated IR-alpha-MSH
      plasma levels measured in melanoma patients. To test this hypothesis, we studied
      the necrosis-related release of MSH from human melanoma cells, using a specific
      radioimmunoassay. The studies of fine-needle biopsies indicated that most of the
      human melanoma tumour exudates tested contained very high MSH concentrations (>
      500 pg/ml; 14/15), while plasma levels were generally normal (< or = 25 pg/ml;
      10/15). The level in an exudate from a non-melanoma tumour type was < 40 pg/ml.
      In vitro studies showed that release of the IR-alpha-MSH was time- and
      temperature-dependent, and related to cell death.

PMID- 9640236
TI  - Why are patients with malignant lymphomas excluded from clinical trials? The
      experience of an oncology institute in Italy.

PMID- 9640237
TI  - Human transplacental passage of the retinoid fenretinide (4HPR)

PMID- 9640238
TI  - Comments on: Haemostatic abnormalities in lung cancer: prognostic implications,
      Buccheri et al., Eur J Cancer, 33, pp. 50-55, 1997.

PMID- 9640239
TI  - Inhibition of an established allergic response to ovalbumin in BALB/c mice by
      killed Mycobacterium vaccae.
AB  - Allergic disorders are mediated by T lymphocytes secreting T helper 2 (Th2)
      cytokines, interleukin-4 (IL-4) and interleukin-5 (IL-5), resulting in high
      levels of serum immunoglobulin E (IgE) and recruitment of eosinophils. One of the
      treatment strategies is to downregulate the Th2 component by inducing a T helper
      1 (Th1) response to the relevant allergen, because Th1 and Th2 cytokines are
      thought to be mutually antagonistic. In this study, we examined the effects of
      Mycobacterium vaccae, a potent inducer of Th1 immunity, on allergic responses in
      a murine model. A single injection of M. vaccae into ovalbumin (OVA)-preimmunized
      BALB/c mice suppressed serum IgE over a wide dose range (10(7), 10(8) or 10(9) M.
      vaccae). Further experiments, using 10(7) M. vaccae injected twice, showed that
      this treatment inhibited not only serum IgE, but also the potential for ovalbumin
      induced IL-5 production by spleen cells. This non-specific ability of a
      mycobacterium to decrease Th2 activity, even when not presented together with the
      allergen, is in agreement with recent epidemiological studies on the impact of
      bacillus Calmette-Guerin (BCG) vaccination, and of other potent Th1 stimuli, on
      the incidence of atopy. The suppression of serum IgE and allergen-specific IL-5
      synthesis by M. vaccae suggest that this organism is likely to have clinical
      application in the immunotherapy of allergy.

PMID- 9640240
TI  - Recognition of a common mycobacterial T-cell epitope in MPB59 of Mycobacterium
      bovis.
AB  - Bovine tuberculosis, which persists as a residual level of infection in many
      European countries, has implications not only for the economy of farming
      communities but also for human health. The aim of this study was to identify a
      common mycobacterial antigen which was recognized in bovine tuberculosis and to
      characterize the response to this antigen at the epitope level. A T-cell clone,
      phenotype CD4+, raised from an animal experimentally infected with Mycobacterium
      bovis was shown to proliferate in response to a panel of sonicates derived from
      different mycobacterial species indicating recognition of an antigen with broad
      specificity. This antigen was subsequently shown to be MPB59. Recognition of
      MPB59 at the epitope level was determined in experimental and field cases of
      bovine tuberculosis using a panel of synthetic peptides (20-mers with 10-residue
      overlaps) incorporating the signal sequence and mature protein. The results
      showed that in vitro interferon-gamma was predominantly produced in response to
      adjacent peptides numbers 10 and 11, suggesting that the dominant epitope was
      contained in the overlap, correlating to residues 101-110 (YYQSGLSIVM). This
      epitope was recognized by 54% of tuberculous cattle of mixed breeds, which
      suggests that it may be genetically permissive in terms of major
      histocompatibility complex presentation. Sequence analysis confirmed that there
      were only minor differences in the amino acid composition within this region for
      various mycobacterial species, which could explain the common T-cell recognition
      described in this study. Common recognition of this epitope indicates that it
      would have limited potential for use as a diagnostic reagent per se but may have
      potential for inclusion in a subunit vaccine.

PMID- 9640241
TI  - In vivo exposure to Porphyromonas gingivalis up-regulates nitric oxide but
      suppresses tumour necrosis factor-alpha production by cultured macrophages.
AB  - The present study was designed to test whether the functional response of mouse
      macrophages elicited by chronic exposure to bacteria will be different from that
      of cells elicited by a non-bacterial irritant. Macrophage elicitation was
      conducted by Porphyromonas gingivalis, a major periodontal pathogen, in
      comparison to a standard elicitation by thioglycollate (TG). We measured
      lipopolysaccharide (LPS)-induced nitric oxide (NO) and tumour necrosis factor
      alpha (TNF-alpha) secretion by the elicited macrophages, and the expression of
      inflammatory cytokines in the whole elicited cell population. In addition, we
      tested the response of TG-elicited macrophages to pretreatment with P. gingivalis
      LPS in vitro. Mouse peritoneal macrophages were harvested 4 days after
      intraperitoneal injection of TG or heat-killed P. gingivalis. TG-elicited
      macrophages produced undetectable levels of TNF-alpha and approximately 0.5
      microM of NO. The stimulation of the macrophages with LPS resulted in the
      secretion of NO and TNF-alpha in a dose-dependent manner. The P. gingivalis
      elicited macrophages produced basal levels of approximately 5 microM NO, but TNF
      alpha was not detectable. LPS stimulation of these cells further increased the
      secretion of NO eightfold while TNF-alpha remained undetectable. The NO secretion
      by P. gingivalis-elicited cells was significantly higher than that by TG-elicited
      cells. Examination of cytokine expression in the whole elicited cell population
      revealed that both P. gingivalis-elicited cells and TG-elicited cells expressed
      messenger RNA for interleukin-2 (IL-2), TNF-alpha and interferon-gamma (IFN
      gamma), but not for IL-4. IL-6 was expressed in P. gingivalis-elicited cells
      only. Pretreatment of TG-elicited macrophages with P. gingivalis LPS for 24 hr
      prior to a second LPS challenge resulted in down-regulation of TNF-alpha
      secretion and up-regulation of NO secretion, a response similar to that seen in
      P. gingivalis-elicited peritoneal macrophages. The results suggest that the in
      vivo exposure of resident macrophages to P. gingivalis induces functional changes
      in peritoneal macrophages. These changes might be due to the effect of P.
      gingivalis LPS.

PMID- 9640242
TI  - In situ study on the pathogenesis and immune reaction of equine herpesvirus type
      1 (EHV-1) infections in mice.
AB  - The mouse model was used to study the pathogenesis of equine herpesvirus type 1
      (EHV-1) after primary and secondary intranasal infections. Within a few hours
      after infection, EHV-1 was found in nasal and olfactorial epithelium and sub
      epithelial cells of the respiratory mucosa, but antigen-specific immune cells
      were never detected. Next to the lung, EHV-1 was transmitted early and directly
      to the brain, both via the olfactory route and the trigeminal nerve, but traces
      of degenerative or inflammatory processes were not detected there. In the lung,
      the immune cells residing or invading the parenchyma did not contain viral DNA or
      proteins. The primary immune response in the lungs was an alveolar and
      interstitial inflammation, dominated by the sequential appearance of neutrophils
      and macrophages, while the number of T and B lymphocytes remained unaltered.
      Within 24 hr after re-infection, lymphocytes accumulated around the blood
      vessels, outnumbering monocytes more than twofold, without neutrophils appearing.
      The lymphocytes comprised of little more B than T cells and the T cells were
      predominantly CD8+ cells. Those and B cells infiltrated the parenchyma. These
      results show the route of virus distribution and demonstrate the lack of antigen
      specific immune cells in the lungs of mice after primary intranasal infection
      with EHV-1.

PMID- 9640243
TI  - The orf virus OV20.0L gene product is involved in interferon resistance and
      inhibits an interferon-inducible, double-stranded RNA-dependent kinase.
AB  - The parapoxvirus orf virus was resistant to type 1 (IFN-alpha) and type 2 (IFN
      gamma) interferons in cultures of ovine cells. The recently identified orf virus
      OV20.0L gene exhibits 31% predicted amino acid identity to the vaccinia virus E3L
      interferon-resistance gene, and is referred to as the (putative) orf virus
      interferon-resistance gene (OVIFNR). The objective of this study was to determine
      whether OVIFNR was involved in interferon resistance. Recombinant OVIFNR as a
      thioredoxin fusion protein (OVIFNR-Tx) inhibited the activation (by
      autophosphorylation) of an interferon-inducible, double-stranded (ds) RNA
      dependent kinase (PKR) of sheep, which was shown to bind dsRNA (poly I:C). PKR in
      other species is involved in the inhibition of protein synthesis as part of the
      antiviral state in infected cells. Virus-infected cell lysates, but not control
      lysates, from cells grown in the presence of cytosine arabinoside also contained
      PKR inhibitory activity, which indicated that the inhibitory activity was
      associated with early viral gene expression. Significantly, the OVIFNR gene
      expressed in interferon-treated ovine fibroblasts protected the unrelated Semliki
      Forest virus from the antiviral effect of both type 1 and type 2 interferons.
      Taken together, the results indicate that the OVIFNR gene functions as an
      interferon-resistance gene, the product of which inhibits PKR in a similar way to
      the vaccinia virus E3L gene product.

PMID- 9640244
TI  - The CD4+ T-cell response to protein immunization is independent of accompanying
      IFN-gamma-producing CD8+ T cells.
AB  - By virtue of their strong bias towards production of interferon-gamma (IFN
      gamma), CD8+ T cells have the potential to promote the development of type 1
      immune responses. We have previously shown that the CD4+ T-cell response to
      immunization with the protein antigen keyhole limpet haemocyanin (KLH) has a
      mixed interleukin-4 (IL-4)/IFN-gamma production profile. Here we show that this
      immunization regimen also stimulates accumulation in the draining lymph nodes of
      CD8+ T cells, which preferentially contain IFN-gamma mRNA ex vivo and secrete IFN
      gamma protein in vitro. This provides a model to test whether CD8+ cell-derived
      IFN-gamma participates in the normal control of the immune response to a non
      viable exogenous antigen. To investigate regulation of the anti-KLH response by
      the CD8+ population or IFN-gamma produced by this or other cell types, mice were
      administered depleting antibodies. Depletion of CD8+ cells had no effect on the
      frequency of clonogenic KLH-specific CD4+ T cells, the IL-4/IFN-gamma profiles of
      their progeny, or the isotype profiles of the serum antibody response to KLH. In
      contrast, IFN-gamma neutralization diminished cell accumulation in the lymph
      nodes and reduced both the frequency of KLH-specific CD4+ T cells that gave rise
      to IFN-gamma-producing clones and serum titres of KLH-specific IgG2a and IgG3.
      Therefore, despite the potential for cross-regulation, the CD4+ T-cell response
      to this immunogen is independent of the IFN-gamma-skewed CD8+ response.

PMID- 9640245
TI  - Kinetics of cytokine and NFAT gene expression in human interleukin-2-dependent T
      lymphoblasts stimulated via T-cell receptor.
AB  - T cells respond to mitogenic or antigenic stimulation by proliferation and by
      turning on cytokine gene expression. Here we have analysed the kinetics and
      nature of cytokine production in human peripheral blood-derived T lymphoblasts
      stimulated with anti-CD3 antibodies or Lens culinaris lectin (LCL). T cells were
      purified from peripheral blood mononuclear cells (PBMC) and primarily activated
      with anti-CD3 antibodies and cultured in the presence of interleukin-2 (IL-2).
      Anti-CD3-restimulated T cells (mainly CD8+) produced IL-2, interferon-gamma (IFN
      gamma) and tumour necrosis factor-alpha (TNF-alpha) and low levels of IL-4 and IL
      10 transcripts and proteins. No IL-6 gene expression was observed. In LCL
      stimulated cells the cytokine production pattern was very similar. Steady-state
      mRNA levels of IL-2, IL-10 and IFN-gamma peaked at 3 hr after anti-CD3
      stimulation and declined rapidly thereafter. The kinetics of TNF-alpha mRNA
      expression was faster, being at its peak level 1 hr after stimulation. Anti-CD3
      stimulated IL-2 gene expression was down-regulated by protein synthesis
      inhibitor, whereas IL-10, IFN-gamma and TNF-alpha genes were readily induced
      independent of ongoing protein synthesis. T-cell receptor stimulation also
      induced a very rapid expression of c-jun, c-fos and NFATc1 (NFATc) genes, the
      gene products of which are involved in cytokine gene expression. In conclusion,
      the cytokines synthesized by IL-2-dependent T cells were predominantly IL-2, IFN
      gamma and TNF-alpha.

PMID- 9640246
TI  - Simultaneous cross-linking of CD6 and CD28 induces cell proliferation in resting
      T cells.
AB  - In the present study, we showed that simultaneous ligation of the monoclonal
      antibodies (mAb) against CD6 and CD28 induces T-cell proliferation in purified
      resting T lymphocytes in the absence of T-cell receptor (TCR) occupancy. No cell
      proliferation was observed when the mAb were cross-linked alone or used
      simultaneously in the soluble form. T-cell proliferation mediated through
      CD6/CD28 is accompanied by the up-regulation of interleukin-2 (IL-2) mRNA and
      expression of IL-2 receptors on the cell surface. In the presence of IL-2
      neutralizing mAb the proliferative response of the T cell induced through
      CD6/CD28 was inhibited dose dependently. Cross-linking mAb to CD6 and CD28 alone
      or together did not down-regulate the CD3/TCR complex. T-cell proliferation
      mediated through CD6/CD28 was only partially blocked by the immunosuppressive
      drug, cyclosporin A (CsA), whereas anti-CD28-induced T-cell proliferation in the
      presence of the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), was
      unaffected. In sharp contrast T-cell proliferation mediated by anti-CD6 in the
      presence of TPA was efficiently blocked by CsA. In addition, two protein kinase C
      (PKC) inhibitors, GF 109203X and H-7 dose-dependently inhibited T-cell
      proliferation mediated through CD6/CD28, suggesting that PKC activation may be
      involved. Furthermore, there was a marked differential dose-dependent inhibitory
      effect of the PKC inhibitors on T-cell proliferation mediated by the co-ligation
      of anti-CD6 or anti-CD28 in the presence of anti-CD3, with the former being more
      sensitive to PKC inhibition. Taken collectively, our results suggest that T-cell
      activation can occur through an antigen-independent pathway by cross-linking the
      accessory molecules, CD6 and CD28, and that these two cell surface antigens may
      have distinct signalling pathways.

PMID- 9640247
TI  - Non-responsiveness of antigen-experienced CD4 T cells reflects more stringent co
      stimulatory requirements.
AB  - We recently reported that previously activated T cells, irrespective of the
      nature of the first stimulus they encountered, are unable to respond to
      Staphylococcal enterotoxin B (SEB), nor to soluble anti-CD3 monoclonal antibody
      (mAb) presented by splenic antigen-presenting cells (APC). Such previously
      activated T cells are, however, fully capable of responding to plate-bound anti
      CD3 plus splenic APC. These data suggest differential integration of the T-cell
      receptor (TCR) and co-stimulatory signalling pathways in naive versus antigen
      experienced T cells. Consistent with this hypothesis, anti-CD28 mAb restores the
      proliferative capacity of resting ex vivo CD45RBlo CD4+ T cells (representing
      previously activated T cells) to both soluble anti-CD3 mAb and SEB.
      Interestingly, mAb-mediated engagement of cytotoxic T-lymphocyte antigen-4 (CTLA
      4) completely negates the rescue effects mediated by anti-CD28 mAb in CD45RBlo
      cells. Nevertheless, the non-responsiveness of CD45RBlo CD4+ T cells cannot be
      reversed by anti-CTLA-4 Fab fragments, indicating that it is not related to
      negative regulatory effects of CTLA-4 engagement itself. Interestingly, the
      addition of interleukin-2 (IL-2) restores the proliferative capacity of CD45RBlo
      CD4+ T cells to SEB and soluble anti-CD3 mAb. Moreover, when rescued by IL-2, the
      cells are less susceptible to the negative regulatory effects of CTLA-4
      engagement. Together, these findings suggest that the non-responsiveness of
      CD45RBlo CD4+ T cells to certain stimuli may be related to inadequate TCR
      signalling, primarily affecting IL-2 production.

PMID- 9640248
TI  - The transmembrane region of CD2-associated signal-transducing proteins is crucial
      for the outcome of CD2-mediated T-cell activation.
AB  - Signalling through the CD2 molecule was shown previously to employ similar
      signalling molecules as the T-cell receptor (TCR). Here, we show that CD2
      mediated signalling is strongly influenced by the expressed transmembrane region
      of the employed signal-transducing molecule. We used TCR-negative cells
      expressing chimeric fusion proteins that consist of human interleukin-2 (IL-2)
      receptor alpha-chain-derived sequences (hCD25) fused to mouse-specific zeta-chain
      segments (hCD25-zeta). One set of TCR-negative cell lines expressed the hCD25
      derived extracellular part fused to mouse-specific transmembrane and cytoplasmic
      zeta-protein sequences ('TZZ'). The second type of cell lines expressed the hCD25
      derived extracellular and transmembrane portions fused to the mouse-specific zeta
      chain cytoplasmic segment ('TTZ'). After cross-linking the hCD25-zeta molecules
      with specific monoclonal antibodies (mAb), all TCR-negative cell lines produced
      similar amounts of IL-2. Cross-linking with stimulating pairs of CD2-specific
      mAb, however, led to IL-2 production only in cell lines expressing the zeta-chain
      specific transmembrane segment. Co-cross-linking of CD25 and CD2 molecules
      resulted in an effective stimulation of both TZZ- and TTZ-expressing cell lines.
      Moreover, TTZ- and TZZ-expressing cell lines differed in their pattern of
      tyrosine-phosphorylated proteins after stimulation with hCD25-specific mAb. Thus,
      although CD2 and TCR molecules share signalling components and pathways, the fine
      tuning of CD2 co-receptor function appears to be regulated in part by
      transmembrane regions of signal-transducing molecules like the TCR-associated
      zeta-chain.

PMID- 9640249
TI  - The CD8+ granzyme B+ T-cell subset in peripheral blood from healthy individuals
      contains activated and apoptosis-prone cells.
AB  - Granzyme B (GrB) has been implicated in induction of apoptosis in target cells.
      The presence of GrB in peripheral blood CD8+ T cells from healthy individuals was
      analysed in immunocytochemical and flow cytometric studies. Furthermore, CD8+ GrB
      T cells and CD8+ GrB+ T cells were compared regarding phenotypical
      characteristics and susceptibility to both spontaneous and Fasmediated apoptosis.
      GrB was expressed by approximately one-fifth of CD8+ T cells. Compared with the
      CD8+ GrB- T-cell subset, the CD8+ GrB+ T-cell subset contained cells that were
      relatively more activated and more prone to spontaneous apoptosis. Culturing of
      cells with immunoglobulin M (IgM) anti-Fas monoclonal antibody had no additional
      effect on the number of CD8+ GrB+ T cells undergoing apoptosis. We suggest that
      the presence of CD8+ GrB+ T cells in peripheral blood from healthy individuals
      results from immune surveillance or contact with infectious agents, and that
      spontaneous apoptosis of these cells might serve as a mechanism for their
      eventual clearance.

PMID- 9640250
TI  - Gene transfer of costimulatory molecules into a human colorectal cancer cell
      line: requirement of CD54, CD80 and class II MHC expression for enhanced
      immunogenicity.
AB  - Colorectal cancer is considered a non-immunogenic malignany. One strategy to
      augment the immunogenicity of such tumours is represented by the expression of
      costimulatory molecules by gene transfer. Using transfected variants of the human
      colorectal cancer cell line SW480 we tested various costimulatory molecules
      (CD80, CD86, CD54) and a class II major histocompatibility complex (MHC) allele
      (HLA-DR3) alone or in combination on their ability to support primary T
      lymphocyte activation in vitro. Expression of CD80 or CD86 similarly as the
      combination of both was not sufficient to induce proliferation of human
      allogeneic T cells. Expression of CD54 together with CD80 strongly augmented the
      costimulatory function of CD80, as observed in the presence of a CD3 monoclonal
      antibody (mAb), but did not lead directly to a T-cell response against modified
      tumour cells. Importantly, SW480 cells coexpressing CD54, CD80 and the HLA-DR3
      allele effectively promoted T-lymphocyte proliferation. Moreover, the use of such
      CD54+/CD80+/HLA-DR3+ SW480 variants for repetitive stimulations resulted in the
      generation of T-cell lines predominantly composed of CD8+ T cells exhibiting
      class I MHC restricted cytolytic activity towards untransfected SW480 tumour
      cells. This demonstrates that the generation of immunogenic tumour cell variants,
      i.e. for the use as cellular vaccines, requires multiple genetic alterations in
      the case of non-immunogenic human tumours cells, such as colorectal cancer cells.

PMID- 9640251
TI  - Emigration of mature T cells from the thymus is inhibited by the imidazole-based
      compound 2-acetyl-4-tetrahydroxybutylimidazole.
AB  - The primary role of the thymus is to provide mature T cells for the peripheral
      immune system. The mechanisms involved in the cellular export processes are as
      yet unknown. In this study, we examined the ability of 2-acetyl-4
      tetrahydroxybutylimidazole (THI), an agent widely used as a component of ammonia
      caramel food colouring, to inhibit T-cell export from the thymus. BALB/c mice
      were maintained on drinking water containing THI for 5 days. The mice showed a
      twofold increase in the total number of mature medullary thymocytes (CD4+CD8- and
      CD4-CD8+) as well as a slight decrease in the total number of immature double
      positive cells (CD4+CD8+). The mature single-positive thymocytes were found to
      express high levels of the homing molecule L-selectin, suggesting that these
      potential emigrants were prevented from leaving the thymus. To confirm this, THI
      treated mice were injected intrathymically with fluorescein isothiocyanate and
      the number of labelled T cells appearing in the lymph nodes and spleen was
      determined 16 hr later. A 10-fold decrease in the number of CD4+ and CD8+ recent
      thymic emigrants in the lymph nodes and spleen of THI-treated mice was observed.
      Previous studies have shown that THI does not affect other aspects of thymocyte
      development, such as proliferation and differentiation. Taken together, these
      results suggest that the immunosuppressive effects of THI may be due, in part, to
      preventing of the final step of T-cell export out of the thymus.

PMID- 9640252
TI  - CD4+ T cells, but not CD8+ T cells, are required for the development of
      experimental autoimmune gastritis.
AB  - Murine autoimmune gastritis, induced by neonatal thymectomy, is characterized by
      a mononuclear infiltrate within the gastric mucosa, loss of parietal and
      zymogenic cells and circulating autoantibodies to the gastric H/K ATPase. The
      infiltrate contains both CD4+ and CD8+ T cells. Here we have investigated the
      roles of CD4+ and CD8+ T cells in the development of gastritis by in vivo
      treatment with depleting rat anti-CD4 and anti-CD8 monoclonal antibodies.
      Depletion of CD4+ T cells decreased the incidence of gastric mononuclear
      infiltrates from 63% (5/8), observed in normal rat immunoglobulin G (IgG)
      injected mice, to 8% (1/12) and also abolished the production of antigastric
      autoantibodies. In contrast, depletion of CD8+ T cells did not reduce the
      incidence of gastritis. The absence of CD8+ T cells in the infiltrate of the
      stomach of anti-CD8(+)-treated mice was confirmed by immunocytochemistry. These
      results argue that neonatal thymectomy-induced autoimmune gastritis is mediated
      by CD4+ T cells and that CD8+ T cells do not play a significant role in the
      development of the gastric lesion.

PMID- 9640253
TI  - An increase in basal glucocorticoid concentration with age induces suppressor
      macrophages with high-density Fc gamma RII/III.
AB  - Ageing is usually accompanied by a decline in immune and neuroendocrine
      functions. To elucidate the mechanisms underlying age-related immunosuppression,
      the functions and surface phenotypes of peritoneal cells in the
      monocyte/macrophage lineage from old mice were investigated. The role of
      glucocorticoids (GC) in the immunomodulation was also examined. Proliferative
      responses of spleen cells from control mice stimulated with concanavalin A (Con
      A) were significantly suppressed by adding peritoneal exudate cells from old
      mice. Flow cytometry analysis revealed that the proportion of MAC-1+ cells with a
      high density of type II or type III receptor for the Fc portion of IgG (Fc gamma
      RII/IIIbright cells) was increased markedly in the periotoneal exudate cells from
      old mice. The prominent suppressor activity for Con A responses of control spleen
      cells was found in the Fc gamma RII/IIIbright cells, whereas MAC-1+ cells with a
      low density of Fc gamma RII/III (Fc gamma RII/IIIdull cells) did not suppress the
      Con A responses. On the other hand, both the basal corticosterone concentrations
      in serum and the mRNA expression for GC receptor in peritoneal exudate cells
      increased significantly in old mice. Furthermore, the proportion of Fc gamma
      RII/IIIbright cells in peritoneal exudate cells from old mice was normalized on
      administration of the GC antagonist RU 38,486 (mifepristone). These results
      suggest that the increase in basal corticosterone concentrations in old mice
      induces the generation of Fc gamma RII/IIIbright suppressor cells, possibly
      leading to the immune-suppressive state.

PMID- 9640254
TI  - Lysis-sensitive targets stimulate an elevation of cAMP in human natural killer
      cells.
AB  - Natural killer (NK) cells are lymphocytes that are capable of destroying tumour
      cells and virally infected cells (cytolysis) without prior sensitization. When
      cAMP is artificially elevated in NK cells, it is a potent inhibitor of their
      cytolytic function. We investigated whether NK-cell cAMP levels are modulated in
      response to tumour target cells to determine the potential of cAMP as a
      physiological regulator of NK cytotoxic function. When NK cells are exposed to a
      range of lysis-sensitive (LS) tumour-target cells there is an increase in
      intracellular cAMP levels in the NK cells over a 60-min period. The peak increase
      in cAMP (200-400% above control) occurs at 30 min for all LS targets tested.
      There is no increase in NK-cell cAMP in response to lysis-resistant (LR) tumour
      target cells. The cAMP elevation may be dependent on both LS-target-stimulated
      adenylyl cyclase (AC) activation and LS-target-stimulated phosphodiesterase (PDE)
      inhibition. When the NK cells are pretreated with the protein tyrosine kinase
      (PTK) inhibitor, genistein (30 micrograms/ml), the AC-activation component of the
      cAMP elevation is abolished. Thus, the AC-activation component appears to require
      PTK activation. When NK cells are pretreated with the protein kinase C (PKC)
      inhibitor, chelerythrine chloride (10 microM) the cAMP elevation in response to
      LS targets was not diminished. This indicates that neither the AC-activation
      component nor any PDE-inhibition component require PKC activation.

PMID- 9640255
TI  - Cloning and sequencing of a cDNA encoding chicken mannan-binding lectin (MBL) and
      comparison with mammalian analogues.
AB  - The serum lectin, mannan-binding lectin (MBL) (also denoted mannan-binding
      protein or mannose-binding protein, MBP) has been identified in mammals (humans,
      monkey, cow, rabbit, mouse and rat). Upon binding to carbohydrates on the surface
      of microorganisms, MBL mediates activation of the complement system, leading to
      killing of the microorganism. MBL thus exerts a role in the innate immune
      defence. We have described the isolation and partial characterization of an
      analogous protein in chicken serum. Oligonucleotides based on the N-terminal
      sequence of this protein were used in a reverse transcription-polymerase chain
      reaction (RT-PCR) with chicken liver RNA as template. The PCR product was
      sequenced and found to encode part of the NH2 terminus of chicken MBL. A perfect
      match probe was synthesized and used to screen a chicken liver cDNA library. The
      isolated clones carried a cDNA insert of 1692 bp with an open reading frame of
      714 bp encoding a mature protein of 238 amino acids including a signal peptide of
      five amino acids. The deduced amino acid sequence agrees with those determined by
      conventional amino acid sequence analysis of the peptides except for four
      residues. We have compared the deduced primary structure of chicken MBL with the
      mammalian analogues. The phylogenetic analysis indicates that the gene
      duplication leading to two different MBL forms in mammals occurred after the
      split from birds and reptiles. This concurs with the finding of only one form of
      MBL in chickens.

PMID- 9640256
TI  - The plasma levels of coglutinin are heritable in cattle and low levels predispose
      to infection.
AB  - Conglutinin, like mannan-binding lectin (MBL) and CL-43, is a serum collection
      involved in the innate immune defence system. In man, low serum MBL
      concentrations, resulting from mutations in the collagen region, are associated
      with a common opsonic defect. Plasma levels of conglutinin in cattle were assayed
      by rocket immunoelectrophoresis to examine whether they were genetically
      determined. Samples were collected from calves (309 bull-calves and 260 heifers
      with complex pedigree relationships). The number of respiratory infections from
      the 42nd to 336th day of life was recorded. The number of infections was found to
      be genetically determined (heritability: h2 = 0.31 +/- 0.07). A wide
      concentration range of conglutinin was found in plasma (< 1.25-35 micrograms/ml
      for females, geometric mean 8.1 micrograms/ml, and < 1.25-47 micrograms/ml for
      males, geometric mean 15.5 micrograms/ml), and the concentrations was found to be
      genetically determined (heritability, h2 = 0.52 +/- 0.07). The analysis revealed
      a negative association between disease frequency and the conglutinin levels (
      0.56 +/- 0.18 for female; -0.50 +/- 0.18 for male). Levels of conglutinin below
      the detection limit of the assay (1.25 micrograms/ml) were found in 2% of the
      animals. If these animals are assumed to be homozygous for a single recessive
      allele causing low concentrations a gene frequency of 0.15 could be calculated.
      These findings suggests that selection for resistance against infectious disease
      is possible in cattle and that the level of plasma conglutinin may be a helpful
      trait in such a breeding scheme.

PMID- 9640257
TI  - Calreticulin associates with non-HLA-A,-B class I proteins in the human
      choriocarcinoma cell lines JEG-3 and BeWo.
AB  - Human placental trophoblast expresses as unusual repertoire of major
      histocompatibility complex (MHC) class I products that appears to reflect the
      unique role of this epithelium in mediating feto-maternal relations during
      pregnancy. Trophoblast is devoid of human leucocyte antigen (HLA)-A,-B antigens
      but can express one or more non-HLA-A,-B class I proteins. The human
      choriocarcinoma cell lines JEG-3, BeWo and JAR are widely used as models to study
      trophoblast. During attempts to isolate non-HLA-A,-B class I from JEG-3 and BeWo
      by immunoaffinity chromatography using a monoclonal antibody to beta 2
      microglobulin we observed a 55,000 MW protein co-purifying with class I. N
      terminal amino acid sequencing and immunoblotting using a specific antiserum
      identified this product as calreticulin, a molecule recently shown to be involved
      in the assembly of classical class I in human B-lymphoblastoid cells. In our
      hands JEG-3 and BeWo were found to express 45,000 MW non-HLA-A,-B class I
      proteins while the 40,000 MW HLA-G product was identified only in JEG-3. Our data
      suggest that calreticulin associates with non-HLA-A,-B class I heterodimers and
      with free 45,000 MW non-HLA-A,-B class I H chains in JEG-3. JAR was found to be
      devoid of detectable class I H chains but contained beta 2-microglobulin and
      calreticulin. However, calreticulin-beta 2-microglobulin complexes were not
      detected in JAR. Calreticulin and class I were apparently co-localized within the
      endoplasmic reticulum of JEG-3 cells whereas only class I was expressed at the
      cell surface. These studies demonstrate that calreticulin is associated with non
      HLA-A,-B class I products in human choriocarcinoma cells.

PMID- 9640258
TI  - Effect of testosterone and cortisol administration on the reproductive tract of
      male Antechinus stuartii (Marsupialia).
AB  - The life history of Antechinus stuartii, a marsupial, is highly synchronized and
      culminates in a brief mating period that is followed by complete male mortality.
      The accessory reproductive tracts of male A. stuartii enlarge in association with
      testosterone and cortisol hormone concentrations, but this appears to be
      unrelated to the spermatogenic cycle. The present study examined the effects of
      testosterone and cortisol on the male reproductive tract. Four groups of adult
      males from May (when plasma testosterone and cortisol concentrations are low)
      were given depot injections of testosterone esters or synthetic cortisol in doses
      that mimic concentrations found in males in the breeding period (August). Males
      were given either saline, testosterone only, cortisol only, or testosterone plus
      cortisol. Experimental groups did not differ in the seminiferous tubule
      morphology. However, the cells from the caudal end of the epididymides of both
      testosterone groups were considerably hypertrophied compared with males treated
      with saline or cortisol only. Testosterone treatment significantly increased
      prostate and bulbourethral gland mass, although addition of cortisol to the
      testosterone administration diminished this effect. The morphology of the
      accessory reproductive tract of males treated with either saline or cortisol only
      was similar to that of untreated males at the same time of year, and the
      morphology of the accessory reproductive tract of males treated with testosterone
      plus cortisol was similar to that of untreated males in the breeding season. Like
      some other marsupials, the spermatogenic cycle in A. stuartii is apparently not
      correlated with androgen activity, while the accessory reproductive tract is
      affected by androgens.

PMID- 9640259
TI  - Role of nitric oxide and cyclooxygenase products in controlling vascular tone in
      uterine microvessels of rats.
AB  - The importance of nitric oxide (NO) and dilator prostaglandins in uterine
      resistance arterioles was investigated. In pentobarbital anaesthetized rats at
      dioestrus-2, the uterine microcirculation in vivo was transilluminated by a
      fibreoptic probe and microvessels (circumferential arterioles) viewed by video
      microscopy. Arteriolar diameters were measured while increasing concentrations of
      acetylcholine (ACh), serotonin (5-HT), phenylephrine (PE), or angiotensin II
      (AII) were applied topically (suffused) over the uterus. Agonists were applied
      alone or with ibuprofen (IBU; cyclooxygenase inhibitor), N omega-nitro-L-arginine
      (L-NA; nitric oxide synthase inhibitor) or both. Circumferential arterioles were
      dilated by ACh and 5-HT (10(-8)-10(-4) mol l-1) and constricted by PE (10(-8)-10(
      5) mol l-1) and AII (10(-11)-10(-7) mol l-1). Suffusion of L-NA or L-NA with
      ibuprofen (10(-4) mol l-1 each) abolished ACh-induced dilation; ibuprofen alone
      blocked dilation at higher ACh concentrations. Serotonin-induced relaxation was
      significantly attenuated by L-NA alone or in combination with ibuprofen.
      Vasoconstriction induced by PE was enhanced by L-NA alone and L-NA with
      ibuprofen, but ibuprofen alone had no effect. In contrast, AII-induced
      constriction was enhanced significantly by ibuprofen or L-NA and further enhanced
      when both ibuprofen and L-NA were present. These results suggest that ACh can
      release either nitric oxide (NO) or cyclooxygenase products to cause uterine
      arteriolar dilation and that 5-HT-induced uterine microvascular relaxation is
      mediated via NO only. They also suggest that PE-induced vasoconstriction is
      attenuated by the release of NO but not cyclooxygenase products and that
      constrictor responses evoked by AII are attenuated by both NO and dilator
      prostaglandin release. Thus, both nitric oxide and dilator prostaglandins are
      important in the control of uterine microvessels.

PMID- 9640260
TI  - Diet-induced loss of cyclic ovarian function at normal body weight in a rodent
      model for bulimia nervosa.
AB  - A bulimic rat model was used to test whether type and frequency of food intake
      mimicking that in human bulimia nervosa could disrupt oestrous cyclicity, induce
      an effect on glycoprotein (LH) structure, or affect both processes and if so, to
      determine whether any such effects were acute, or persisted after return to
      normal eating patterns. Voluntary hyperphagia was induced by offering female rats
      a varied and palatable choice of human food items--the 'cafeteria diet'. There
      were four groups: control (normal chow), obese (continuous cafeteria diet), post
      obese (cafeteria diet, then fasted to reduce weight to that of controls) and
      binge (cafeteria alternated with normal diet every few days). Animals were
      maintained on these diets for 60 days (phase I). They were then given a GnRH
      challenge on day 2 of dioestrus of the cycle. Twenty-four hours later, half of
      the animals in each group were killed for assessment of effects on their
      reproductive organs. The remaining animals were returned to normal diets and kept
      for a further 40 days, when the GnRH challenge was repeated and the animals were
      killed 24 h later (phase II). All animals on the cafeteria diet in phase I
      exhibited significant disruption of oestrous cyclicity irrespective of body
      weight. LH released in response to the first GnRH challenge showed a prolonged
      half-life, and/or increased rate of secretion in the obese and post-obese groups
      but in the binge group the secretory/clearance properties resembled those of
      control animals. After the second GnRH challenge at the end of phase II, however,
      the LH of the binge group appeared to have different secretory or clearance
      characteristics, whereas that of the previously obese animals had returned to
      normal. These data show ovarian cyclicity was disrupted by hyperphagia and
      irregular eating, even at normal body weight. Relating ovarian function to
      pituitary output in terms of LH, the effects of the continuous cafeteria diet did
      not appear to persist in the animals that returned to normal diets, but in the
      binge group the effect, presumably of the diet manipulation, was manifested after
      return to a normal eating pattern. This finding suggests that irregular eating
      habits may exert a direct (and acute) effect on the ovary, but that effects on
      the pituitary (and LH glycoforms) take longer to be expressed, explaining many
      features of bulimia nervosa.

PMID- 9640261
TI  - Oxytocin- and aluminium fluoride-induced phospholipase C activity and
      prostaglandin F2 alpha secretion during the ovine luteolytic period.
AB  - A series of studies was conducted to characterize changes in components of the
      cell signalling cascade that mediates oxytocin-induced prostaglandin F2 alpha
      (PGF2 alpha) synthesis at the onset of luteolysis in sheep. In the first
      experiment, caruncular tissue was dissected from 20 ewes on days 12-15 of the
      oestrous cycle, and incubated for the measurement of phospholipase C (PLC)
      activity or secretion of PGF2 alpha. Activation of GTP-binding proteins with
      aluminium fluoride stimulated both inositol phosphate accumulation and PGF2 alpha
      secretion on all days examined. However, oxytocin did not stimulate PLC activity
      or PGF2 alpha accumulation until day 13. While the ability of oxytocin to
      stimulate PLC activity increased after day 13, oxytocin-induced PGF2 alpha
      secretion declined slightly from day 13 to 15, suggesting that cell signalling
      components downstream from PLC modulate the response to oxytocin after day 13.
      Oxytocin failed to stimulate PGF2 alpha synthesis on day 14 after oestrus.
      Secretion of endogenous luteal oxytocin may have rendered uterine tissues
      collected on day 14 refractory to oxytocin in vitro. Therefore, a second study
      was conducted in ovariectomized, steroid replaced ewes. Ovarian steroids were
      administered to mimic endogenous changes in progesterone and oestradiol. The
      temporal patterns of PGF2 alpha synthesis in response to oxytocin and
      pharmacological agents were similar to uterine tissues from cyclic ewes in the
      first experiment; however, the magnitude of the response was less. These data
      suggest that oxytocin receptors are absent or are not coupled to PLC until day 13
      after oestrus.

PMID- 9640262
TI  - Localization of follistatin in the rat testis.
AB  - The cellular localization of the activin-binding protein, follistatin, in the rat
      testis has been a matter of some controversy with different investigators
      claiming that Sertoli cells, Leydig cells or germ cells are the primary cell
      types containing this protein. The localization of mRNA encoding follistatin was
      re-examined using reverse transcription-polymerase chain reaction (RT-PCR) and in
      situ hybridization as well as the distribution of follistatin by
      immunohistochemistry. The results demonstrate that mRNA encoding follistatin is
      located in many germ cells including type B spermatogonia, primary spermatocytes
      with the exception of the late leptotene and early zygotene stages, and
      spermatids at steps 1 to 11. It is also found in Sertoli cells and endothelial
      cells but not in Leydig cells. Immunohistochemistry, using two different antisera
      to follistatin, showed that this protein was localized to spermatogonia, primary
      spermatocytes at all stages except the zygotene stage, spermatids at all stages
      and to endothelial cells and Leydig cells in the intratubular regions. The
      failure to detect mRNA for follistatin in Leydig cells using RT-PCR and in situ
      hybridization suggests that the immunohistochemical localization in these cells
      reflects binding of follistatin produced elsewhere. The widespread localization
      of follistatin, taken together with its capacity to neutralize the actions of
      activin, may indicate that follistatin modulates a range of testicular actions of
      activin, many of which remain unknown.

PMID- 9640263
TI  - Depletion of vitamin C from pig corpora lutea by prostaglandin F2 alpha-induced
      secretion of the vitamin.
AB  - The luteolytic effects of prostaglandin F2 alpha (PGF2 alpha) are thought to be
      mediated in part by the promotion of an increasingly oxidative cellular
      environment. Loss of antioxidants is one mechanism by which PGF2 alpha might
      induce or exacerbate oxidative damage within the corpus luteum. This study was
      performed to establish whether depletion of vitamin C is an acute effect of PGF2
      alpha on the pig corpus luteum and to gain insight into the mechanism of luteal
      vitamin C loss at luteolysis. Gilts (n = 4) were anaesthetized and both utero
      ovarian veins and an ear vein were catheterized. Each corpus luteum on the
      treated ovary received an intraluteal injection of PGF2 alpha (1 microgram)
      followed by a sustained release implant containing 100 micrograms of the
      prostaglandin. The other ovary served as the control and each corpus luteum
      received corresponding volumes of injection vehicle and blank implant. Blood was
      collected from the ear vein and both utero-ovarian veins every 15 min beginning
      15 min before the onset of treatment. Collection of blood stopped when animals
      were ovariectomized and corpora lutea were collected at 2 h after treatment.
      Progesterone and vitamin C (ascorbate) concentrations were measured in tissue and
      plasma samples. PGF2 alpha-treated luteal tissue had similar progesterone, but
      significantly lower ascorbate, concentrations when compared with control corpora
      lutea. PGF2 alpha treatment resulted in a rapid and sustained increase in plasma
      ascorbate within the treatment-side utero-ovarian vein, while the control utero
      ovarian vein and ear vein showed little change in plasma ascorbate during the
      experimental period. No effect of PGF2 alpha on plasma progesterone was evident.
      This finding suggests that PGF2 alpha depletes the pig corpus luteum of vitamin C
      by inducing secretion of the vitamin into the bloodstream. Further studies are
      necessary to determine whether the depletion of vitamin C that is induced by PGF2
      alpha contributes to the demise of the pig corpus luteum.

PMID- 9640264
TI  - Effect of acute treatment with progesterone on the timing and synchrony of
      ovulation in Bos indicus heifers treated with a norgestomet implant for 17 days.
AB  - The aim of the present study was to develop a treatment protocol for the precise
      synchronization of oestrus that would avoid the development of persistent
      dominant ovarian follicles. Bos indicus heifers, in which oestrous cycles had
      been presynchronized, were allocated randomly, according to the day of their
      oestrous cycle, to one of five treatment groups. All heifers received a
      subcutaneous ear implant containing 3 mg of norgestomet for 17 days starting on
      day 0 and an injection of an analogue of prostaglandin F2 alpha on days 0 and 4.
      Heifers in group 1 (control group; n = 7) received no other treatment, while
      heifers in groups 2 (n = 8), 3 (n = 7), 4 (n = 7), and 5 (n = 7) received a
      single progesterone-releasing controlled internal drug release device (CIDR) for
      24 h on days 10, 12, 14 and 16, respectively. Treatment with a single CIDR
      delayed the mean time of ovulation and the day of emergence of the ovulatory
      follicle in heifers treated on days 14 and 16 compared with control heifers (P <
      0.05). There was less variation in the interval to ovulation in heifers treated
      on day 10 compared with other treated heifers (P < 0.05). The variation among
      heifers in the day of emergence of the ovulatory follicle and the age of the
      ovulatory follicle at ovulation was less for all groups treated with a CIDR than
      for the control group (P < 0.05). The duration of dominance and variation in the
      duration of dominance of the ovulatory follicle was less in heifers treated with
      a CIDR device on days 10 and 16 than for control heifers (P < 0.05). Mean age
      (days from emergence to ovulation) of the ovulatory follicle did not differ among
      treatment groups (P > 0.05). Concentrations of LH and oestradiol decreased
      coincident with increased concentrations of progesterone on the days of CIDR
      treatment in treated compared with control heifers (P < 0.02) but increased again
      after removal of the CIDR. A smaller proportion of follicles in the growing phase
      of follicular development at the time of CIDR treatment become atretic compared
      with follicles that had reached a plateau phase of follicular growth (14.3% (1/7)
      versus 90.5% (19/21), respectively; P < 0.001). It was concluded that acute
      treatment with progesterone can influence the growth pattern of ovarian
      follicular development. However, the effect varies with the stage of ovarian
      follicular development. Short term treatment with progesterone 7 days before the
      end of a 17 day period of norgestomet treatment resulted in precise synchrony of
      ovulation without the ovulation of a persistent dominant ovarian follicle.

PMID- 9640265
TI  - Anti-Mullerian hormone (AMH) secretion in prepubertal and adult rams.
AB  - The aim of the present analysis was to determine whether anti-Mullerian hormone
      concentrations in prepubertal plasma or adult rete testis fluid are related to
      the number or function of Sertoli cells in rams or to the presence of the FecB
      Booroola gene. Twenty rams from two Booroola crosses, differing in their
      testicular masses were analysed; in each cross, half of the animals were
      heterozygous carriers of the FecB gene. The data from rams, during prepuberty and
      at adulthood during the non-sexual season, were analysed by two-way ANOVA and
      residual correlations. In 4-week-old intact male lambs, the mean anti-Mullerian
      hormone plasma concentration was 15 ng ml-1, irrespective of cross, genotype or
      eCG stimulation; it was significantly negatively correlated with FSH (r = -0.51;
      P = 0.02; n = 19). In adults, anti-Mullerian hormone was not detectable in plasma
      and was 0.5 ng ml-1 in rete testis fluid, irrespective of cross or genotype. The
      total number of Sertoli cells per testis was not related to anti-Mullerian
      hormone concentration in lamb prepubertal plasma or in adult rete testis fluid.
      The concentration of anti-Mullerian hormone in adult rete testis fluid was
      significantly and negatively correlated with the daily production of leptotene
      primary spermatocytes per testis (r = -0.56; P = 0.02; n = 16). The mean
      oestrogen concentration in the adult testicular vein was 2 pg ml-1 and was
      correlated negatively with the rete testis fluid concentration of anti-Mullerian
      hormone (r = -0.60; P = 0.02; n = 15) and correlated positively with the daily
      production of leptotene primary spermatocytes per testis (r = 0.53; P < 0.05; n =
      19). In conclusion, anti-Mullerian hormone secretion was not correlated with the
      total numbers of Sertoli cells per testis and cannot be used as a predictor of
      the number of Sertoli cells. Anti-Mullerian hormone secretions were not affected
      by the presence of FecB gene. However, anti-Mullerian hormone secretion could be
      considered to be inversely related to the daily production of primary
      spermatocytes by the testis.

PMID- 9640266
TI  - Differential localization of laminin chains in bovine follicles.
AB  - The composition of a basal lamina markedly affects its ability to filter material
      and affects the fate of adjacent epithelial cells. Therefore, basal laminae
      differ in composition with tissue development, and between different tissues in
      the body. Laminins are a component of basal laminae and consist of one alpha, one
      beta and one gamma chain, of which there are at least five, three and two
      isoforms, respectively. This is the first study to immunolocalize a range of
      these individual laminin chains (alpha 1, alpha 2, beta 1, beta 2, gamma 1) in
      ovarian follicles. Frozen sections of bovine ovaries (n = 6) were immunostained
      using specific antisera to laminin chains and factor VIII-related antigen (to
      identify endothelial cells). Secondary antisera were labelled with one of two
      different fluorochromes (DTAF and Cy3), and dual localization of laminin chains
      and factor VIII-related antigen was performed. The alpha 1, beta 2 and gamma 1
      chains were consistently localized to the follicular basal lamina in all healthy
      follicles. Staining was less intense in the atretic antral follicles. Conversely,
      alpha 2 and beta 1 were rarely present in the follicular basal laminae of healthy
      antral follicles. Two of nine healthy antral follicles observed stained weakly
      for alpha 2 in their basal lamina, and beta 1 was present at low concentrations
      in growing preantral follicles. In atretic antral follicles, the follicular basal
      lamina stained positively for alpha 1, alpha 2, and beta 2 but no beta 1 was
      detected and the gamma 1 staining was less intense than in healthy follicles.
      Antisera to Englebreth Holm-Swarm tumour laminin stained basal laminae of all
      follicles. In the theca of antral follicles, beta 1 and beta 2 chains were both
      present in the vasculature. Staining for the gamma 1 chain was present in the
      thecal vasculature and generally throughout the theca of healthy and atretic
      antral follicles. Therefore, the composition of the follicular basal lamina
      alters during development and atresia, and potentially plays a role in the
      changing identity of the granulosa cells and the accumulation of antral
      follicular fluid.

PMID- 9640267
TI  - Stimulation of ovarian oxytocin secretion and uterine prostaglandin release by
      exogenous progesterone early in the cycle of the ovarian auto-transplanted ewe.
AB  - The present study was undertaken to determine whether the administration of
      progesterone, early in the oestrous cycle, had an influence on ovarian oxytocin
      secretion and on peripheral concentrations of the prostaglandin F2 alpha
      metabolite 13,14-dihydro-15-keto PGF2 alpha (PGFM) in the ovarian auto
      transplanted ewe. Twelve ewes with ovarian auto-transplants (n = 6 per group)
      were randomly assigned to receive an i.m. injection of progesterone (12.5 mg) or
      vehicle, twice a day, on days 1, 2 and 3 of the oestrous cycle. Beginning on day
      7, blood samples were collected at intervals of 1 h from the ovarian and
      contralateral jugular veins for up to 70 h. Ovarian oxytocin secretion rate and
      jugular concentrations of PGFM and progesterone were determined by
      radioimmunoassay. The number of ewes that showed pulses of both ovarian oxytocin
      and PGFM was significantly (P < 0.05) greater in progesterone-treated ewes than
      in control ewes. In progesterone-treated ewes, the average number of ovarian
      oxytocin pulses per ewe was 9.66 +/- 5.5 (mean +/- SD) and the interval between
      pulses was 7.18 +/- 5.8 h. The mean amplitude and amount of oxytocin released, as
      calculated by the area under the curve of ovarian oxytocin pulses, were 6.27 +/-
      1.98 ng min-1 and (10.05 +/- 8.91 ng min-1)tau, respectively (where tau is the
      number of hours between the last time point before and the first time point after
      a significant increase in hormone concentration was detected by the Pulsar
      program). The mean amplitude and area under the curve of PGFM pulses were 317.22
      +/- 5.65 pg ml-1 and (383.36 +/- 1.77 pg ml-1)tau, respectively. The average
      number of pulses of plasma PGFM observed per ewe was 5.8 +/- 1.9 and interpulse
      interval for plasma PGFM pulses was 10.32 +/- 8.7 h between day 7 and day 9 after
      oestrus. These data indicate that administration of progesterone during the first
      3 days of the oestrous cycle results in the premature release of ovarian oxytocin
      and uterine prostaglandin F2 alpha.

PMID- 9640268
TI  - Development of oestrogen receptor expression and hormone response in the uterus
      of the bovine fetus.
AB  - The objective of the present study was to determine the temporal expression of
      oestrogen receptor alpha in the uterus of the developing bovine fetus. Bovine
      fetuses were collected and approximate gestational age was determined by crown
      rump measurement. Fetal uteri were either snap frozen in dry ice-ethanol, or
      placed in sterile Dulbecco's modified Eagle's medium. Fetal uteri (n = 20) were
      homogenized and cytosolic oestrogen receptor measured by [3H]ligand binding
      assay. Total RNA was extracted from fetal uteri (n = 53) and amplified by reverse
      transcription-polymerase chain reaction using primers specific for the oestrogen
      receptor, progesterone receptor, interleukin 1 alpha, interleukin 6, transforming
      growth factor beta, prolactin receptor, epidermal growth factor receptor,
      retinoic acid receptor isoforms alpha, beta, and gamma, or glyceraldehyde-3
      phosphate dehydrogenase (loading control). Expressed as a ratio with
      glyceraldehyde-3-phosphate dehydrogenase, mRNA encoding oestrogen receptor was
      identified in fetal uteri throughout the period from day 65 to day 200, and was
      increased from day 100 to day 185 (P < 0.003); uterine samples from day 100 to
      day 200 expressed interleukin 1 alpha, interleukin 6, transforming growth factor
      beta, prolactin receptor, epidermal growth factor receptor and retinoic acid
      receptor isoforms alpha, beta, and gamma, but did not express detectable mRNA
      encoding progesterone receptor. Despite the presence of mRNA encoding oestrogen
      receptor, [3H]oestradiol binding was not detected until after day 155. Fetal
      uterine explants collected at days 100-110 (n = 3) or at days 185-200 (n = 3)
      were cultured in the presence of oestradiol (1.0 nmol l-1, or vehicle); there was
      a significant effect of oestradiol treatment on specific mRNA expression at days
      185-200 (P < 0.014), but not at days 100-110 (P = 0.71). It is concluded that
      mRNA encoding oestrogen receptor is constitutively expressed at least from day 65
      in the uterus of the bovine fetus, but that oestrogen receptor alpha protein and
      a functional oestrogen response are not present until late in the second third of
      pregnancy.

PMID- 9640269
TI  - Doppler ultrasonography of canine maternal and fetal arteries during normal
      gestation.
AB  - Two-dimensional ultrasonography was used in combination with colour-flow imaging
      and pulsed wave Doppler ultrasonography to study the maternal circulation and the
      development of fetal vascularization in six Beagles during normal gestation. For
      the first time, the development of the circulation was demonstrated in the bitch
      and her fetuses intra vitam. The bloodstream was examined in small uteroplacental
      arteries, the umbilical artery, the fetal aorta and the common carotid artery.
      The duration of the study was from week 3 after insemination until birth.
      Relatively large vessels were detected by cross-sectional ultrasonography, and
      small vessels were detected by colour-flow imaging. In pulsed wave Doppler
      ultrasonography, the blood flow was measured and described using the parameters
      of systolic peak velocity, diastolic peak velocity, end-diastolic velocity,
      pulsatility index, resistance index, A:B ratio (systolic peak velocity:end
      diastolic velocity) and S:D parameter (systolic peak velocity:diastolic peak
      velocity). The development of the measured parameters is typical and similar to
      that in humans. The systolic peak velocity of the canine maternal uteroplacental
      arteries shows important differences in comparison with humans. The pulsatility
      index, resistance index and A:B ratio decrease in nearly all vessels. Only the
      fetal common carotid artery has constant pulsatility and resistance indices
      during gestation. For the first time, the quality and quantity of the normal
      blood flow have been monitored during the whole of gestation. A normal
      circulation is fundamental for supplying the fetus adequately with oxygen and
      nutrients and thus for physiological development. These ultrasonographic results
      are the basis for further clinical studies.

PMID- 9640270
TI  - Differential effects of oestradiol and progesterone on proliferation and
      morphology of cultured bovine uterine epithelial and stromal cells.
AB  - The effect of oestrogen and progesterone on the proliferation of cultured bovine
      uterine epithelial and stromal cells was assessed. Epithelial and stromal cells
      recovered from cows at day 1 to day 3 of the oestrous cycle were cultured in RPMI
      medium supplemented with 5% steroid-free fetal calf serum for 4 and 8 days. The
      addition of progesterone to the culture medium altered the morphology of stromal
      cells. Oestradiol (0.1-10 nmol l-1) and progesterone (50 nmol l-1) significantly
      increased the total DNA (from 9.6 +/- 0.96 to 25.6 +/- 0.99 micrograms per well,
      P < 0.001) and protein content (from 76.6 +/- 2.6 to 125.8 +/- 2.6 micrograms per
      well, P < 0.001) and decreased the ratio of protein to DNA (from 8.0 +/- 0.24 to
      4.9 +/- 0.24, P < 0.01) in stromal cells during the first 4 days. During the
      second 4 days, the relative percentages of increase in DNA content were not
      affected by steroids, indicating that the major effect of steroids on stromal
      cell proliferation was exerted during the first 4 days of incubation. The
      morphology of epithelial cells was not influenced by the addition of steroids.
      DNA content of epithelial cells was reduced by the addition of oestrogen (from
      22.9 +/- 2.1 to 15.0 +/- 2.0 micrograms per well, P < 0.01), but not progesterone
      (from 22.9 +/- 2.1 to 25.8 +/- 2.0 micrograms per well, P > 0.05). Total protein
      content of epithelial cells was reduced by oestradiol by day 4 (from 111.0 +/-
      6.2 to 71.0 +/- 6.2 micrograms per well, P < 0.01), but not by day 8 (from 305.0
      +/- 10.5 to 296.0 +/- 10.5 micrograms per well, P > 0.05). Progesterone increased
      the total protein content (from 305.0 +/- 10.5 to 366.0 +/- 10.5 micrograms per
      well, P < 0.01). Oestradiol significantly enhanced the ratio of protein to DNA in
      epithelial cells at day 8 (from 10.1 +/- 1.0 to 16.8 +/- 1.0, P < 0.01). These
      results show that oestradiol and progesterone have different effects on the
      proliferation and morphology of epithelial and stromal cells in vitro.

PMID- 9640271
TI  - Creatine metabolism in the seminiferous epithelium of rats. I. Creatine synthesis
      by isolated and cultured cells.
AB  - The testis synthesizes creatine from both arginine and glycine precursors, but
      when rat testicular tissue is separated into seminiferous tubules and
      interstitial cells, creatine synthesis occurs only in the tubular fraction. The
      purpose of the work presented here was to define the locus of creatine synthesis
      within the seminiferous tubules, by using cell separation and culture techniques
      to examine synthesis in the Sertoli cells and germ cells. The total creatine
      content, in the cellular compartment and incubation medium, of Sertoli-germ cell
      co-cultures and of Sertoli cell-enriched cultures, largely free of germ cells,
      increased by similar amounts over a 24 h incubation period. Sertoli cell-enriched
      cultures incorporated radioactivity from L-[guanidino-14C]arginine and [1
      14C]glycine into both creatine and its biosynthetic precursor, guanidinoacetic
      acid. Isolated germ cells did not incorporate radioactivity from L-[guanidino
      14C]arginine into either creatine or guanidinoacetic acid when incubated at a
      similar density and protein concentration under similar conditions. It is
      concluded that the synthesis of creatine observed in isolated rat seminiferous
      tubules occurs within the Sertoli cells and not the germ cells.

PMID- 9640272
TI  - Creatine metabolism in the seminiferous epithelium of rats. II. Effect of
      modulators of cellular biochemical function on creatine secretion by cultured
      Sertoli cells.
AB  - The Sertoli cells have been identified as the primary locus for creatine
      synthesis within the seminiferous epithelium. The purpose of the studies reported
      here was to examine the effect of modulators of Sertoli cell function on creatine
      secretion by primary cultures of these cells. Sertoli cell-enriched cultures,
      maintained in a defined medium, secreted creatine into the incubation medium in a
      manner that was linear with time over at least 6 h, but which had reached a
      plateau within 24 h. Secretion was stimulated by physiological and toxicological
      modulators of Sertoli cell function. Incubation of Sertoli cell-enriched cultures
      in the presence of FSH (> or = 40 mU ml-1), dibutyryl cyclic AMP (> or = 0.1 mmol
      l-1), mono-(2-ethylhexyl) phthalate (> or = 1 mumol l-1) or cadmium (> or = 3
      mumol l-1) increased the secretion of creatine into the incubation medium by at
      least 85% over 24 h. Creatine secretion by Sertoli cell-enriched cultures,
      incubated over 4 h in a balanced salt solution, was independent of exogenous L
      glutamine. However, the stimulation of secretion induced by 1 mmol dibutyryl
      cyclic AMP l-1 was dependent on the presence of 4 mmol L-glutamine l-1 in the
      incubation medium, which suggests that an increase in creatine secretion occurs
      as a consequence of stimulated glutamine oxidation.

PMID- 9640273
TI  - Concentrations of oxytocin in the intercavernous sinus of mares during
      luteolysis: temporal relationship with concentrations of 13,14-dihydro-15-keto
      prostaglandin F2 alpha.
AB  - The reproductive tracts of nine thoroughbred mares were examined by ultrasound to
      determine the day of ovulation (day 0). Mares were fitted with intercavernous
      sinus cannulae on the day before the start of sample collection of pituitary
      venous effluent rich in oxytocin. Intercavernous sinus blood samples were
      collected for at least 36 h at 5 min intervals beginning at noon on day 13 (n =
      2), day 15 (n = 5) or day 16 (n = 2) after ovulation. Concentrations of oxytocin
      and 13,14-dihydro-15-keto prostaglandin F2 alpha (PGFM) in plasma were determined
      by radioimmunoassay. Three high-magnitude surges of PGFM (> 1 ng ml-1) were found
      in these samples. Three high magnitude pulses of oxytocin (> 200 pg ml-1) were
      also observed, one associated with each of the PGFM surges. In each of these
      cases, the oxytocin pulse appeared to follow or coincide with the onset of the
      PGFM surge. Lower magnitude pulses of both hormones were detected throughout the
      bleeding period in every mare. The average interval between these pulses was
      122.3 min for oxytocin and 121.0 min for PGFM. The interval between pulses for
      individual mares varied from 90 to 199 min for oxytocin, and from 87 to 213 min
      for PGFM. However, there was no correlation between PGFM and oxytocin pulse
      intervals among mares. Within each mare, there was no discernable association
      between low magnitude pulses of oxytocin and PGFM. From these data, it was
      concluded that high-magnitude surges of PGF2 alpha are associated with similar
      surges of oxytocin from the posterior pituitary gland, and that PGF2 alpha may
      induce their secretion. The posterior pituitary gland also appears to secrete
      oxytocin in a pulsatile manner at a frequency of approximately 1 pulse every 2 h
      but these pulses do not appear to be associated with the low magnitude pulses of
      PGF2 alpha secreted from the uterus.

PMID- 9640274
TI  - Central metabolic messengers and the effects of nutrition on gonadotrophin
      secretion in sheep.
AB  - Nutrition influences the reproductive axis via alteration of gonadotrophin
      secretion. However, a link between nutrition and the secretion of GnRH, which
      drives the axis, has yet to be established. The aim of the present study was to
      measure the change in the concentrations of metabolic substances in the
      cerebrospinal fluid of adult male sheep offered a diet designed to maintain
      constant gonadotrophin secretion (Group M; n = 6), or a diet known to increase
      gonadotrophin secretion (Group M + L; n = 6). On days 1, 3 and 10 of the dietary
      treatments, cerebrospinal fluid and jugular blood were sampled and analysed for
      metabolic fuels (glucose, amino acids and free fatty acids) and metabolic
      hormones (insulin, insulin-like growth factor I, GH, prolactin, cortisol and the
      thyroid hormones). On day 11 of the dietary treatment, LH pulse frequency and
      mean FSH concentrations in Group M + L had increased relative to Group M and to
      day 0. Plasma concentrations of prolactin and insulin on days 3 and 10, and
      glucose and insulin-like growth factor I on day 10, were higher in Group M + L
      than in Group M, but only cerebrospinal fluid concentrations of insulin, glucose
      and certain amino acids were affected by the dietary treatments on days 3 and 10.
      Cerebrospinal fluid, but not plasma, concentrations of aspartate, tyrosine,
      cystine, phenylalanine and arginine on day 3, and glutamine, gamma-aminobutyric
      acid, threonine, alanine on days 3 and 10, were higher in Group M + L relative to
      Group M. On day 10, plasma and cerebrospinal fluid concentrations of arginine,
      phenylalaine, proline, tyrosine, methionine and phosphoserine, but only the
      plasma concentrations of linoleic acid, aspartate and serine, were higher in
      Group M + L than in Group M. Concentrations of triiodothyronine, thyroxine, and
      cortisol in plasma and cerebrospinal fluid were not affected. These results show
      that the nutritional stimulation of gonadotrophin secretion is accompanied
      primarily by fluctuations in plasma and cerebrospinal fluid concentrations of
      insulin and certain amino acids, which suggests that, when nutritional status is
      improved, insulin, amino acids and possibly glucose interact to modulate GnRH
      secretion.

PMID- 9640275
TI  - Dog epididymis-specific mRNA encoding secretory glutathione peroxidase-like
      protein.
AB  - A differential library screening procedure was used to clone a novel abundant and
      tissue-specific cDNA from the dog epididymis. It was tentatively named CE7 for
      dog epididymal gene product 7. By sequence similarity to homologous counterparts
      expressed in mice, rats, pigs, and macaque monkeys, it appears that the 1.5 kb
      dog epididymal mRNA encodes the secretory glutathione peroxidase-like protein,
      GPX5. This protein is very similar to the family of glutathione peroxidase
      enzymes, but does not contain selenocysteine. Northern blot and in situ
      hybridization analyses revealed that the mRNA encoding CE7/GPX5, like its species
      homologues, was restricted to the epididymis and transcribed by the epithelial
      cells in the proximal parts of the organ. While the CE7 cDNA probe cross
      hybridized to epididymal mRNAs in most species included in this study, it failed
      to identify a human GPX5 counterpart. Northern blot analyses of epididymal RNA
      extracts from hemi-cryptorchid dogs suggested that testicular secretions,
      including androgen hormones, temperature effects, or both, were involved in the
      region-dependent modulation of mRNA encoding CE7 in the dog epididymis. The
      effect was most obvious in the caput region of the abdominal organ where the mRNA
      encoding CE7 was almost completely downregulated.

PMID- 9640276
TI  - Proteolysis of insulin-like growth factor-binding proteins (IGFBPs) within the
      pig uterine lumen associated with peri-implantation conceptus development.
AB  - Pig conceptuses undergo morphological development from spherical to filamentous
      forms during days 10 to 12 of pregnancy, coincident with a high content of mRNAs
      encoding insulin-like growth factor (IGF)-I in the uterine endometrium and
      secretion of IGF-I into the uterine lumen. The potential regulation by developing
      conceptuses of the bioavailability of IGF-binding proteins (IGFBPs) within the
      uterine microenvironment was investigated. Uterine luminal flushings (ULFs) were
      obtained between days 10 and 18 of pregnancy and the presence of specific IGFBPs
      was detected by ligand blot analysis. ULFs collected at days 10 and 11 of
      pregnancy contained 46 and 43 kDa IGFBP-3, several IGFBPs of about 30 kDa
      including IGFBP-2, and an unidentified 26 kDa IGFBP; IGFBP-3 was the most
      abundant. By day 12, however, IGFBPs were substantially diminished or
      undetectable. Examination of the morphology of flushed conceptuses revealed that
      the loss of IGFBPs in ULF was associated with the transition from spherical to
      filamentous morphology. The abundance of IGFBP-3 mRNA in uterine endometrium, as
      monitored by blot-hybridization, was not altered in a similar way, suggesting
      that lack of IGFBP-3 in 'filamentous' ULF resulted from proteolysis rather than
      from decreased expression of the IGFBP-3 gene. Consistent with this, incubation
      of 'spherical' ULF with or without added 'filamentous' ULF at 37 degrees C
      resulted in the disappearance of endogenous IGFBP-3 only in 'spherical +
      filamentous' ULF. The protease activity in 'filamentous' ULF was inhibited by
      EDTA, but unlike matrix metalloproteinases, was not zinc ion-dependent or
      inhibited by 1,10-phenanthroline. Moreover, this activity was partially inhibited
      by the serine protease inhibitor aprotinin, but not by 4-(2-aminoethyl)
      benzenesulfonyl fluoride (AEBSF), a known inhibitor of plasmin. The IGFBP
      protease activity of ULF may therefore comprise a group of enzymes including an
      unidentified serine protease. The results suggest that elongating pig conceptuses
      induce IGFBP protease activity which may increase the intrauterine
      bioavailability of IGF.

PMID- 9640277
TI  - Effect of follicle size and of the FecB Booroola gene on oocyte function in
      sheep.
AB  - Booroola ewes have a major gene that affects ovulation rate. Gene expression has
      consequences on ovarian somatic cells but it is unknown whether it also affects
      germ cells in the adult ovary. Hence, the present study examined (1) whether
      oocyte growth was similar in FecBFecB and Fec+ Fec+ oocytes during preantral and
      antral follicular growth, (2) whether the patterns of proteins neosynthesized by
      oocytes of these two genotypes were identical, (3) whether the ability of the
      oocytes to resume meiosis was unaffected by genotype and (4) whether, after IVF,
      oocytes from both genotypes could develop to the blastocyst stage at similar
      rates. Histological examination of the respective sizes of the oocyte and of the
      follicle demonstrated that oocytes were larger in FecBFecB versus Fec+ Fec+
      preantral follicles. Resolution of the proteins neosynthesized by FecBFecB and
      Fec+ Fec+ oocytes by one-dimensional PAGE and image analysis demonstrated that
      quantitative (but not qualitative) differences could be observed between
      genotypes for bands at 74, 59, 35 and 25 kDa. In addition, a genotype by oocyte
      size interaction was detected for two additional bands at 45 and 43 kDa. After 24
      h of culture in vitro in TCM-199 plus 100 ng ml-1 FSH plus 10% sheep follicular
      fluid, oocytes from FecBFec+ follicles gained the ability to resume meiosis at a
      smaller size and a higher proportion of them reached metaphase II irrespective of
      the size class studied compared with Fec+ Fec+ follicles. In addition, the
      developmental rate of eggs after IVF was also affected by follicle size and
      genotype, since FecBFec+ oocytes originating from 1.0-3.5 mm follicles had a
      greater ability (P < 0.05) to develop to the blastocyst stage than Fec+ Fec+
      oocytes. It is concluded that the FecB gene, in addition to its effects on
      granulosa cell maturation, also affects oocyte development and function. Whether
      these alterations are related requires further investigation.

PMID- 9640278
TI  - Expression of RNA from developmentally important genes in preimplantation bovine
      embryos produced in TCM supplemented with BSA.
AB  - This study investigated the effects of a semi-defined culture system on the
      temporal pattern of expression of RNA from genes involved in compaction and
      cavitation: gap junction protein connexin43 (Cx43), desmosomal glycoproteins
      desmoglein 1 (Dg 1), desmocollins I, II and III (Dc I, Dc II, Dc III), desmosomal
      protein plakophilin (Plako); metabolism glucosetransporter-1 (Glut-1); RNA
      processing poly(A)polymerase (PolyA); heat shock protein 70.1 (HSP); and
      trophoblastic function trophoblast protein (TP) in bovine oocytes and embryos
      generated in vitro using TCM199 supplemented with BSA as the culture medium.
      Morulae and blastocysts derived in vivo were collected from superovulated heifers
      and also used for this study. Poly(A)+ RNA was extracted from pools of 20-50
      oocytes or embryos, analysed by reverse transcription-polymerase chain reaction
      and the amplified fragments were verified by sequencing. Assays were repeated at
      least three times for each developmental stage and provided consistent results in
      all replicates. In bovine embryos produced in vitro, mRNA encoding Cx43 was
      detectable up to the morula stage, whereas blastocysts and hatched blastocysts
      did not express this gene. No transcripts were found for Dg 1 and Dc I throughout
      the tested preimplantation stages. Dc II and Dc III transcripts were found from 2
      4-cell embryos up to the hatched blastocyst stage. mRNA encoding Plako was
      detected in immature and mature oocytes and zygotes, while no transcripts were
      seen in 2-4-cell and 8-16-cell embryos. The gene was expressed again from the
      morulae to the hatched blastocyst stage. Oocytes and bovine embryos produced in
      vitro showed transcripts for Glut-1, PolyA and HSP throughout preimplantation
      development up to the hatched blastocyst stage. The gene encoding TP was
      transcribed only in blastocysts and hatched blastocysts. Morulae and blastocysts
      produced in vivo showed the same expression as their in vitro counterparts, with
      one exception: the in vivo embryos transcribed Cx43. The results of this study
      reveal for the first time the transcriptional pattern of a set of 'marker' genes
      involved in various processes in early bovine embryonic development. Transferable
      morulae and blastocysts produced in vitro expressed most genes similar to their
      in vivo counterparts. These data contribute to the molecular characterization of
      this widely used in vitro culture system for bovine embryos and provide a major
      advance towards production of 'physiologically normal' embryos.

PMID- 9640279
TI  - Photoperiod-induced phase-shifts of the endogenous clock controlling reproduction
      in the rainbow trout: a circannual phase-response curve.
AB  - Different groups of winter-spawning female rainbow trout that had been maintained
      under seasonally changing daylength and temperature were exposed to 2 months of
      continuous light at different times of the year. The same photoperiod produced
      advances in the time of spawning of up to 232 days and delays of up to 80 days,
      depending upon the timing of exposure in relation to the phase of the
      reproductive cycle. The proportion of fish spawning in each group varied from 18%
      to 100%, again dependent on the timing of exposure to continuous light. The
      photoperiod-induced changes in spawning time can be interpreted as phase
      dependent phase-shifts of an endogenous circannual clock controlling maturation.
      It is proposed that long days, occurring earlier or later than they would under a
      natural photoperiod, were perceived as indications that the clock was running
      slow or fast, thus initiating corrective forward adjustments (advance phase
      shifts) or backward adjustments (delay phase-shifts), respectively. Collectively,
      these responses can be described in the form of a circannual phase-response
      curve.

PMID- 9640280
TI  - Introducing an integrated imaging delivery system in Manitoba.
AB  - OBJECTIVE: As a result of the reform of a comprehensive government health plan,
      an integrated imaging system is being created in the province of Manitoba. The
      intent of the system is to reduce costs, avoid causing harm to patients, enhance
      physician referral services and add new programs. METHODS: Evaluation of trends
      in examinations, equipment, personnel, expenditures and policy in the 1992-93 and
      1995-96 fiscal years in Manitoba. RESULTS: The population has remained steady, at
      1.1 million. Hospitals have been amalgamated under new authorities, and
      Manitoba's annual health care spending of $1.8 billion has been reduced by $235
      million. Between the 2 years, use of radiography declined from 835,748 to 726,394
      examinations per year. Use of mammography, ultrasonography, computed tomography,
      magnetic resonance imaging and nuclear medicine increased moderately. The total
      number of radiologic examinations declined from 1,069,579 to 975,044. There was
      little change in equipment, but the plant aged as a result of freezes on
      construction and capital spending. Personnel declined by 20 full-time equivalent
      positions, from 794.3 in 1992-93 to 774.3 in 1995-96. Savings in operations were
      made as a result of hospital budget restrictions. Total expenditures declined
      from $100 million to $89 million. The income of imaging specialists did not
      change because they were paid higher fees for examinations involving newer
      technology. CONCLUSION: Integration of rural/northern and urban hospital services
      has followed the plan set out in recent legislation. Savings of up to 20% are
      expected to be realized through reduction in personnel (saving $1 million), group
      tendering ($1 million), in-house repair ($1 million), reduction in deployment of
      equipment ($3 million), integration of services ($1 million), indirect cost
      reduction ($5 million), practice guidelines ($3.5 million), reduced breast
      screening costs ($1 million), physician payment reform ($1 million) and rigorous
      clinical/fiscal audit ($1 million).

PMID- 9640281
TI  - Metformin and contrast media: where is the conflict?
AB  - Intravascular administration of iodinated contrast media to patients who are
      receiving metformin, an oral antidiabetic agent, can result in lactic acidosis.
      However, this rare complication occurs only if the contrast medium causes renal
      failure, and the patient continues to take metformin in the presence of renal
      failure. Because metformin is excreted primarily by the kidneys, continued intake
      of metformin after the onset of renal failure results in a toxic accumulation of
      this drug and subsequent lactic acidosis. To avoid this complication, metformin
      must be withheld after the administration of the contrast agent for 48 hours,
      during which the contrast-induced renal failure becomes clinically apparent. If
      renal function is normal at 48 hours, the metformin can be restarted. There is no
      scientific justification for withholding metformin for 48 hours before
      administration of the contrast medium, as currently recommended in the package
      insert. The authors review the pharmacology of metformin and present a
      departmental policy for managing patients with diabetes who receive metformin and
      who require intravascular administration of iodinated contrast media.

PMID- 9640282
TI  - Consultation skills in radiology: a qualitative study.
AB  - OBJECTIVE: Consultation is an important part of radiologic practice. Recently,
      many concerns have been expressed about the lack of emphasis on consultation
      skills as part of the training requirements for radiologists. In order to improve
      the teaching and assessment of trainees, we designed a qualitative study to
      specify the consultation skills expected from a trainee by the end of residency.
      METHODS: Three successive focus groups were held with professors of radiology,
      residents in radiology, and referring physicians. Participants were asked to
      identify the various competencies required from radiologic consultants (1)
      spontaneously, (2) by reacting to a previously generated list, and (3) by
      reacting to common clinical problems encountered in radiology. RESULTS:
      Consultation skills thus identified were organized in a framework consisting of 2
      groups: observable skills and standards of practice. Observable skills were
      subdivided into 5 "problem-setting" skills and 6 "results-management" skills.
      Seven qualities and attitudes identified were combined under the rubric
      "standards of practice." CONCLUSION: The specification of these abilities and
      competencies through a consensus process should permit the teaching of these
      skills and their evaluation through objective, structured clinical examinations.

PMID- 9640283
TI  - Gestational breast cancer.
AB  - OBJECTIVE: To study the problems of breast imaging in gestational breast cancer.
      PATIENTS AND METHOD: Retrospective review of the charts of 19 patients with
      breast cancer detected during pregnancy or lactation or within 1 year of
      delivery, who were referred to a tertiary centre for adjuvant therapy between
      1986 and 1996. For 10 patients who underwent breast imaging, mammograms and
      breast ultrasonograms or reports were requested from outside facilities. RESULTS:
      The patients ranged in age from 23 to 41 years (mean 31 years). All 19 patients
      presented with palpable tumours; in 7 patients, the tumours were stage T2 or
      higher; in 11 patients, the tumours were at an advanced stage with positive
      axillary nodes. In 11 of the patients there was a delay in diagnosis, which
      ranged from 2 to 16 months. Of the 8 mammograms that could be reviewed, 5 showed
      infiltrating ductal carcinomas with typical features, which were detected as a
      mass (in 1 case), a mass with microcalcifications (in 1 case),
      microcalcifications (in 2 cases) and asymmetry (in 1 case). Three mammograms were
      negative, including 1 obtained from a patient with extensive comedocarcinoma.
      Breast ultrasonograms obtained from 4 patients (2 of whom also had mammograms)
      showed solid hypoechoic masses; in 2 of the ultrasonograms, the masses simulated
      a benign lesion. CONCLUSIONS: Although breast cancer during pregnancy and
      lactation is rare, this study suggests that radiologists should include it in the
      differential diagnosis of a solid breast mass seen during pregnancy or lactation.
      Clinicians appear to be reluctant to use breast imaging in these patients;
      however, this can lead to a delay in diagnosis. Ultrasonography is the modality
      of choice for initial analysis of such a mass in this age group. Mammography with
      shielding of the abdomen is recommended if there is suspicion of cancer.
      Clinical, mammographic and sonographic findings should be integrated for optimum
      interpretation.

PMID- 9640284
TI  - Aneurysm of coronary artery bypass graft presenting as a mediastinal mass: case
      report.

PMID- 9640285
TI  - Choroidal melanoma metastasis as a rare cause of cerebellopontine angle lesion: 2
      case reports.

PMID- 9640286
TI  - Coats' disease (exudative retinopathy): case report.

PMID- 9640287
TI  - Comparison of digital angiographic images with conventional radiographs for
      detection of pneumothorax after needle biopsy of lung.
AB  - OBJECTIVE: To compare the rate of detection of pneumothoraces from images
      obtained from a digital angiographic system (1024 x 1024 matrix) and from
      conventional film-screen chest radiographs, following fine-needle biopsy of the
      lung. PATIENTS AND METHOD: For 102 patients who underwent fine-needle biopsy, 2
      digital fluoroscopic chest images and 1 film-screen chest radiograph were
      obtained during expiration after the biopsy. The images were interpreted by 4
      blinded readers. RESULTS: There were 30 pneumothoraces, of which 96.6% were
      detected from standard chest radiographs and 54.2% were detected from digital
      images. CONCLUSIONS: The detection of pneumothorax from digital images was far
      inferior to that from standard film-screen chest radiographs. Therefore, standard
      chest radiographs are recommended after fine-needle biopsy of the lung.

PMID- 9640288
TI  - Check-valve pneumatocele formation following fully treated tuberculosis: case
      report.

PMID- 9640289
TI  - Residents' corner. Answer to case of the month #55. Intrathoracic extramedullary
      hematopoiesis secondary to idiopathic myelofibrosis.

PMID- 9640290
TI  - Telehealth in home care practice.

PMID- 9640291
TI  - North Central West Virginia Nursing Workforce Network.

PMID- 9640292
TI  - Creating value for patients. A legal perspective.

PMID- 9640293
TI  - Developing a nursing outcomes measurement tool.
AB  - In an era of rapidly shifting resources and changing models of care, healthcare
      providers must demonstrate quality and cost-effective patient care. Historically,
      quality of care has been described using administrative variables such as
      mortality, morbidity, length of stay, readmissions, and cost. Methods have not
      been readily available to define quality in terms of the effect of care delivery
      on the health of patients. Combined administrative and health-related databases
      are foundational to outcome infrastructures evolving with the electronic medical
      record. Nursing leaders in a large health maintenance organization sponsored the
      development of the Health Status Outcome Dimensions (HSOD) instrument. The HSOD
      instrument includes measures of functional status, knowledge, and engagement in
      healthcare and the patient and family psychosocial well-being. This article
      describes the processes used and the challenges faced in the development of the
      HSOD instrument. The current status of the HSOD instrument is described, as well
      as its planned future development.

PMID- 9640294
TI  - Nurse executives' leadership roles. Perceptions of incumbents and influential
      colleagues.
AB  - The authors present a leadership profile of employed nurse executives (NEs).
      Interviews and survey data show that the typical NE is a married, middle-aged
      woman who has a masters degree in clinical nursing and extensive clinical
      experience. When comparing NEs' and influential colleagues' perceptions of the
      effectiveness of NEs leadership skills, the former rate themselves higher than
      the latter, and both groups perceive that NEs' leadership styles are more "task
      motivated" than "relationship motivated." The authors apply these findings to the
      career planning of NEs, chief executive officers, and educators in healthcare
      fields.

PMID- 9640295
TI  - Disaster preparedness pays off.
AB  - Last spring, the Red River Valley of North Dakota and Minnesota was devastated by
      an unprecedented flood. Flooding caused foundations to collapse and houses to
      float away or become severely damaged by the raging, sewage-filled water. The
      river displaced people from their homes, and caused significant disruption of
      services including water, power, and medical care for 18 days. Find out how a
      medical contingency plan enabled staff members at the only trauma center and the
      largest clinic in the region to evacuate safely and effectively nearly 1,000
      patients and senior residents in 36 hours, while setting up critical services
      across the region to care for the 50,000 displaced residents of the flood
      disaster.

PMID- 9640296
TI  - The changing nature of organizational commitment in the acute care environment.
      Implications for nursing leadership.
AB  - The downsizing of the acute care sector of healthcare is providing hospital
      nursing staff with fewer alternative employment options in the areas in which
      they currently work. This greater employment uncertainty is likely to affect the
      variables that organizational behaviorialists have found to both enhance or
      detract from the organizational commitment that staff members feel toward the
      organization. The author analyzes the latent effects of the progressive changes
      being sustained in acute care work markets that influenced nurses' perceived
      levels of organizational commitment in earlier times. The research conducted in
      this field by both nursing and other disciplines is reviewed, and implications
      are proposed.

PMID- 9640297
TI  - Bowen's family systems theory. A useful approach for a nurse administrator's
      practice.
AB  - Two concepts from Bowen's family systems theory are differentiation of self and
      triangles. These concepts are presented and recommended as useful tools for the
      nurse a administrator. By using the principles from differentiation of self,
      nurse administrators may improve the work environment by distinguishing between
      their own thoughts and feelings. Once a nursing administrator identifies and
      changes triangulation processes, healthy relationship patterns may occur and
      staff absenteeism and low morale may be improved.

PMID- 9640298
TI  - Community collaboration. The nursing administrator's role in implementing a child
      abuse prevention program.
AB  - The increasing incidence of child abuse is a national disaster. One proposed
      intervention is prevention through a public health nurse home visitation program
      developed and extensively researched by David Olds. Selected components of the
      conceptual model of community collaboration developed by Polivka are applied to
      the implementation process. The role of the public health nursing administrator
      in collaboration, human resource management, and delegation is discussed.

PMID- 9640299
TI  - Kidney disease in Australian aboriginals: time for decisive action.

PMID- 9640300
TI  - Wernicke's encephalopathy and thiamine fortification of food: time for a new
      direction?

PMID- 9640301
TI  - Australian medical research: more resources and the right balance.

PMID- 9640302
TI  - An epidemic of renal failure among Australian Aboriginals.
AB  - OBJECTIVE: To define recent trends (1993-1996) in incidence of endstage renal
      disease (ESRD) among Australian Aboriginal people in the Top End of the Northern
      Territory (NT). DESIGN: Analysis of hospital and clinical records of the Darwin
      based ESRD treatment program from 1993 to 1996 and comparison with data
      accumulated since 1978. PARTICIPANTS: All people entering the ESRD treatment
      program from 1978 to 1996. MAIN OUTCOME MEASURES: Number of patients treated for
      ESRD; their ethnicity, age and sex; comorbidities in Aboriginal patients;
      treatment methods and outcomes. RESULTS: More Aboriginal people presented with
      ESRD between 1993 and 1996 (87) than in the previous 15 years of the program
      (68). The incidence of ESRD in Aboriginals reached 838 per million in 1996, and
      is doubling every 4 years. Aboriginal people presenting with ESRD are younger
      than non-Aboriginal people with ESRD, and, in contrast to non-Aboriginals, ESRD
      rates are higher in women than men. The numbers and proportions of Aboriginal
      ESRD patients who have hypertension, type 2 diabetes and cardiac disease are
      rising. Haemodialysis remains the most common form of treatment, and the number
      of dialysis treatments is doubling every 2.5 years. Only 9% of Aboriginal
      patients entering the program in 1993-1996 were treated with chronic ambulatory
      peritoneal dialysis and only 3% received transplants. Despite their younger age,
      survival of Aboriginal people on dialysis is low (median 3.3 years v. 6.5 years
      in non-Aboriginals), and graft survival after transplant is poor (37% at 5 years
      v. 88% in non-Aboriginals). Survival has not improved in the past 4 years, with
      fewer deaths from infection offset by more deaths from cardiovascular disease.
      CONCLUSIONS: The predicted doubling of ESRD incidence among Aboriginal people by
      the year 2000 will add an enormous burden to limited resources. Risk factors for
      renal disease underlie all the excess morbidity and mortality in NT Aboriginal
      adults, and arise out of accelerated lifestyle changes and socioeconomic
      disadvantage. Better living conditions and education, robust and integrated
      primary healthcare programs, and systematic screening for early renal disease and
      treatment of those with established disease are all matters of urgency.

PMID- 9640303
TI  - Prevalence of Wernicke-Korsakoff syndrome in Australia: has thiamine
      fortification made a difference?
AB  - OBJECTIVE: To determine the prevalence of the Wernicke-Korsakoff syndrome (WKS)
      in Australia and compare this with previous studies. DESIGN AND SETTING:
      Prospective autopsy study at the New South Wales Institute of Forensic Medicine,
      1996-1997. METHODS: Brains of deceased people (aged over 15 years) derived from
      2212 sequential autopsies performed between 1 January 1996 and 31 December 1997
      were studied macroscopically and microscopically to identify cases of WKS. MAIN
      OUTCOME MEASURES: Standard histological criteria for WKS and any available
      clinical data. RESULTS: Twenty-five cases of WKS were identified (prevalence,
      1.1%), mostly among the 5.9% of the 2212 people who had a history suggestive of
      alcohol abuse. Only four cases (16%) had been diagnosed during life. CONCLUSIONS:
      There has been a significant reduction in the prevalence of WKS in Australia
      since the introduction of thiamine enrichment of bread flour. While the
      prevalence is still higher than in most other Western countries, further research
      is needed before adding thiamine to alcoholic beverages can be recommended.

PMID- 9640304
TI  - Measles-mumps-rubella and hepatitis B vaccination uptake in adolescents: a survey
      in metropolitan Melbourne.
AB  - OBJECTIVE: To measure the uptake of preadolescent measles-mumps-rubella (MMR) and
      adolescent hepatitis B vaccinations and assess the influence of certain
      demographic factors on the uptake of these vaccines. DESIGN: Prevalence surveys
      of uptake rates of preadolescent (school Year 6; age 10-11 years) MMR and
      adolescent (school Year 9; age 13-14 years) hepatitis B vaccination. SETTING:
      City of Darebin, an inner northern metropolitan region of Melbourne, 1996.
      SUBJECTS: 1160 Year 6 school students (580 boys) and 1102 Year 9 school students
      (548 boys). INTERVENTION: School-based vaccination program administered by
      Darebin Council. RESULTS: 83% of Year 6 students were vaccinated with the MMR
      vaccine (84.1% of girls and 81.9% of boys). 71.6% of Year 9 students completed
      the full course of hepatitis B vaccination (68.9% of boys and 74.2% of girls).
      There was a higher uptake of MMR in non-government primary schools, but no other
      demographic factors (sex, economic status, non-English-speaking background,
      parental education, school class size) were associated. CONCLUSIONS: These uptake
      rates do not meet National Health and Medical Research Council (NHMRC)
      recommendations. Further study is required to determine and quantify the factors
      that affect vaccination uptake in adolescence. Programs may then be developed to
      improve vaccination uptake.

PMID- 9640305
TI  - Haemolytic-uraemic syndrome outbreak caused by Escherichia coli O111:H-: clinical
      outcomes.
AB  - In South Australia in 1995, we treated 20 children with haemolytic-uraemic
      syndrome associated with Escherichia coli O111:H-. The source of the outbreak was
      contaminated locally produced semi-dry fermented sausage (mettwurst). One child
      died of multiple haemorrhagic cerebral infarcts. Eighteen children required renal
      dialysis (for a median of 14 days); 12 months after discharge five still had
      significant impairment of renal function. Other major complications included
      colonic necrosis (3), cerebral haemorrhage/infarction (3), convulsions (4), and
      glucose intolerance (2). Although E. coli O111:H- has been associated with
      sporadic cases of haemolytic-uraemic syndrome, this was the first large outbreak
      reported in Australia.

PMID- 9640306
TI  - Casemix funding in Australia.
AB  - Casemix funding for hospitals with the use of diagnosis-related groups (DRGs),
      which organise patients' conditions into similar clinical categories with similar
      costs, was introduced in Australia five years ago. It has been applied in
      different ways and to a greater or lesser extent in different Australian States.
      Only Victoria and South Australia have implemented casemix funding across all
      healthcare services. Attempts have been made to formally evaluate its impact, but
      they have not met the required scientific standards in controlling for
      confounding factors. Casemix funding remains a much-discussed issue. In this
      Debate, Braithwaite and Hindle take a contrary position, largely to stimulate
      policy debate; Phelan defends the casemix concept and advocates retaining its
      best features; and Hanson adds a plea for consumer input.

PMID- 9640307
TI  - Essential gastroenterology for the non-gastroenterologist.

PMID- 9640308
TI  - Acute viral hepatitis.
AB  - Most cases of acute hepatitis are caused by hepatitis viruses A, B or C.
      Diagnosis rests on the risk factor history and serological tests. In seronegative
      cases, consider other agents, such as Epstein-Barr virus and cytomegalovirus,
      drug reactions and autoimmune hepatitis. Hepatitis A and B can be prevented by
      appropriate use of highly effective, safe vaccines. Acute liver failure is an
      uncommon, devastating complication of acute viral hepatitis; continued vomiting,
      prolongation of prothrombin time and clouding of consciousness are indications
      for urgent transfer to a liver transplant unit. Hepatitis A is a simple,
      enterically transmitted illness that does not cause chronic hepatitis. 95% of
      adults recover from acute hepatitis B, whereas infection with hepatitis B virus
      acquired in childhood usually becomes chronic.

PMID- 9640309
TI  - Managing somatoform disorders.
AB  - The management of somatoform disorders is a confusing and difficult area. There
      are many iatrogenic complications, including unnecessary and repetitive
      investigations and surgery, drug dependence and "doctor shopping". Somatisation
      is a world wide phenomenon and a common presentation of psychological distress.
      Three main groups of patients are encountered in general practice: those with
      high levels of somatic symptoms, those with illness fear, and those with somatic
      presentations of other psychiatric illnesses. Management is straightforward for
      the acute cases and consists of trying to get the patient to accept a link
      between the psychosocial conflicts and the symptoms. Management is very difficult
      for chronic cases, where care, not cure, is the goal, as is an attempt to limit
      harm to the patient and limit the cost to the health system.

PMID- 9640310
TI  - GM-CSF and wound healing.

PMID- 9640311
TI  - Rationing in Australian health care services.

PMID- 9640312
TI  - Stress management and counselling in primary care.

PMID- 9640313
TI  - Echinacea-associated anaphylaxis.

PMID- 9640314
TI  - Treating stingray wounds with onions.

PMID- 9640315
TI  - Indications for liver transplantation.

PMID- 9640316
TI  - Once is enough--why some women do not continue to participate in a breast cancer
      screening programme.
AB  - AIM: To assess the reasons why many women who have been screened once in a breast
      screening programme decline an invitation for further screening. METHODS:
      Telephone interview survey of a sample of such women; for questions relating to
      their experience of previous mammography, comparison to data on a representative
      sample of first screen attendees. The subjects were women who had attended the
      first round of the Otago-Southland breast cancer screening programme in 1991
      1994, who were eligible for re-screening but had been rescreened; age range 50
      62. RESULTS: From programme records, 86% of women who were eligible for a second
      screen accepted it. Of the women not recorded as having had a second screen, some
      had attended for a second screen; some had not been invited until they had become
      age ineligible and some had received no invitation for re-screening. Of women who
      had received and declined an invitation for re-screening (n = 81), the major
      reason (46%) was their previous mammogram being painful. Other factors
      contributing were illness in themselves or their spouse, practical difficulties
      arranging time and negative experiences with staff in the previous mammography,
      although these related to relatively few women. A few women thought mammography
      would be of no benefit, and a few thought re-screening was unnecessary because
      their first mammography had been normal, or because they practise self
      examination. CONCLUSIONS: Ensuring that all women eligible for further screening
      do get invited could substantially increase the re-screening rate. Even women who
      have declined previous invitations should be offered further invitations, as a
      substantial proportion with to be screened. Flexible and convenient appointment
      times are the main modifiable logistic issue. The major factor influencing non
      participation with further screening is a painful experience of mammography.
      Innovative approaches, either to reduce the pain or to reduce the impact of the
      pain on the woman's attitude to re-screening, should be trialed.

PMID- 9640317
TI  - Current airway clearance techniques.
AB  - In recent times, airway clearance has become an increasingly important part of
      the treatment of patients with excessive bronchial secretions, especially those
      with cystic fibrosis. The number of airway clearance techniques available has
      also grown considerably, becoming increasingly more specific. This has allowed
      patients a greater choice of treatment techniques and has led to a subsequent
      rise in independence. This paper gives a brief overview of the methods of airway
      clearance currently being used by physiotherapists in New Zealand. To date, no
      one method has been shown to be more effective than another. It is imperative
      therefore, that those involved in respiratory care have a clear understanding of
      the airway clearance techniques available. This will allow us to provide out
      patients with the best possible treatment option.

PMID- 9640318
TI  - Paediatric exploratory ingestions of paracetamol.
AB  - AIM: To review paediatric exploratory ingestions of paracetamol presenting to
      Christchurch Hospital Emergency Department. METHOD: A retrospective review of all
      paediatric patients presenting with paracetamol ingestion over a 12 month period.
      RESULTS: During the study period there were 88 paediatric presentations for
      possible toxic ingestions involving paracetamol and 85 of these were exploratory
      self-ingestion. The male to female ratio was 43:42 and the mean age was 35
      months. Paracetamol suspension was ingested in 79/85 cases and tablets in 6/85.
      The mean four hour plasma level was 162 mumol/L and all levels were well below
      the possible toxic level (1300 mumol/L). There was very poor correlation between
      estimated dose ingested and plasma level. CONCLUSION: Toxicity from paediatric
      exploratory ingestion of paracetamol is extremely rare. To reduce the potential
      for poisoning, bottles and prescriptions of paracetamol should have less than a
      total dose of 4 g. The authors recommend that unwitnessed exploratory ingestions
      of paracetamol in children require no treatment if the estimated maximum ingested
      dose is below 140 mg/kg. Above this dose, treatment is based on the result of a
      plasma paracetamol level drawn four hours after ingestion. Gastrointestinal
      decontamination should be reserved for the rare occasions of a definite witnessed
      ingestion of a dose exceeding 140 mg/kg.

PMID- 9640319
TI  - What do general practitioners do when patients present with symptoms indicative
      of urinary tract infections?
AB  - AIM: The primary aim of the study was to examine whether the results of
      laboratory investigations of midstream urine samples from patients with suspected
      urinary tract infection influenced management by general practitioners. METHOD:
      Eleven general practitioners in the Network participated in the study by
      recording treatment and outcomes for consecutive patients with symptoms of
      urinary tract infection. RESULTS: Data from 216 patients were included in the
      study. Dipsticks were used to test the urine of 98 patients (45%) and midstream
      urine samples were sent to the laboratory for 176 patients (82%). Antibiotics
      were prescribed for 176 patients (82%). Antibiotics were prescribed for 95% of
      patients with symptoms of dysuria, frequency and urgency. Where the laboratory
      results showed infection there was no change in treatment after the general
      practitioners received the results for 75 patients (85%). Among those patients
      where the laboratory reported no infection there was no change in treatment after
      the general practitioner received the results for 53 patients (87%). CONCLUSIONS:
      The results of laboratory investigation of midstream urine samples did not change
      the treatment provided for the majority of patients in the study.

PMID- 9640320
TI  - Experience of the upright breast stereotactic core biopsy method and histological
      correlation with surgical biopsy.

PMID- 9640321
TI  - Pathological fracture in an 87-year-old woman.

PMID- 9640322
TI  - Tamoxifen for breast pain.

PMID- 9640323
TI  - Youth suicide rates.

PMID- 9640324
TI  - Statins.

PMID- 9640325
TI  - Ischaemic nephropathy.

PMID- 9640326
TI  - Pharmac--what next?

PMID- 9640327
TI  - Hepatitis TT virus is present in New Zealand.

PMID- 9640328
TI  - Xenopus Smad7 inhibits both the activin and BMP pathways and acts as a neural
      inducer.
AB  - Smads are proteins that transduce signals on behalf of members of the TGF beta
      superfamily of growth factors. Recently, inhibitory Smads, Smad6, Smad7, and Dad,
      were isolated from human, mouse, and fly. These anti-Smads were shown to inhibit
      TGF beta signaling by stably associating to TGF beta type I receptors or, as it
      was shown for Smad6, by binding to receptor-activated Smad1. We report the
      cloning, distribution, and embryological activity of the Xenopus Smad7 (XSmad7).
      We report that XSmad7 inhibits signaling from the activin and BMP pathways in
      animal explants although at different thresholds. When expressed in the embryo,
      low concentrations of XSmad7 dorsalize the ventral mesoderm, thus inducing a
      secondary axis. At higher concentrations however, XSmad7 inhibits both mesoderm
      induction and primary axis specification. In addition, we show that XSmad7 acts
      as a direct neural inducer both in the context of ectodermal explants and in
      vivo. We discuss the implications of these findings in the biochemical context of
      the activin and BMP pathways as well as their implications in mesodermal, neural,
      and axis specification.

PMID- 9640329
TI  - Disregulation of ocular morphogenesis by lens-specific expression of FGF-3/int-2
      in transgenic mice.
AB  - FGF-3, originally named int-2, was discovered as an oncogene frequently activated
      in mammary carcinomas resulting from the chromosomal integration of the mouse
      mammary tumor virus (MMTV). Int-2 was later designated FGF-3 based on sequence
      homology with other members of the fibroblast growth factor (FGF) family. FGF-1
      is the prototypical member of the FGF family, and is the only family member which
      activates all known FGF receptor isoforms. Transgenic mice expressing in the lens
      a form of FGF-1 engineered to be secreted show premature differentiation of the
      entire lens epithelium. In contrast, transgenic mice engineered to secrete FGF-2
      in the lens do not undergo premature differentiation of the lens epithelium (C.
      M. Stolen et al., 1997, Development 124, 4009-4017). To further assess the roles
      of FGFs and FGF receptors in lens development, the alpha A-crystallin promoter
      was used to target expression of FGF-3 to the developing lens of transgenic mice.
      The expression of FGF-3 in the lens rapidly induced epithelial cells throughout
      the lens to elongate and to express fiber cell-specific proteins including MIP
      and beta-crystallins. This premature differentiation of the lens epithelium was
      followed by the degeneration of the entire lens. Since FGF-1 and FGF-3 can both
      activate one FGF receptor isoform (FGFR2 IIIb) that is not activated by FGF-2,
      these results suggest that activation of FGFR2 IIIb is sufficient to induce fiber
      cell differentiation throughout the lens epithelium in vivo. Furthermore,
      transgenic lens cells expressing FGF-3 were able to induce the differentiation of
      neighboring nontransgenic lens epithelial cells in chimeric mice. Expression of
      FGF-3 in the lens also resulted in developmental alterations of the eyelids,
      cornea, and retina, and in the most severely affected transgenic lines, the
      postnatal appearance of intraocular glandular structures.

PMID- 9640330
TI  - Alteration in connexin 43 gap junction gene dosage impairs conotruncal heart
      development.
AB  - Connexin 43 (Cx43) knockout mice and transgenic mice (CMV43) overexpressing the
      Cx43 gap junction gene exhibit heart defects involving the conotruncus and right
      ventricle. Based on the heart phenotype and Cx43 gene and transgene expression
      pattern, we previously proposed that the heart defects may reflect a role for gap
      junctions in the modulation of cardiac neural crest development. To further
      elucidate the mechanism by which these heart defects may arise, fetal heart
      structure and function in these transgenic and knockout mice were examined by
      magnetic resonance microscopy and Doppler echocardiography. Magnetic resonance
      microscopy of E14.5 fetuses revealed an enlargement of the right ventricular
      chamber in the heterozygous Cx43 knockout and CMV43 transgenic mice. This was
      accompanied by thinning of the chamber wall. In the homozygous Cx43 knockout
      mouse, heart malformation was also restricted to the right ventricle. This was
      generally characterized by two pouches at the base of the pulmonary outflow
      tract, but occasionally hearts with a single pouch were found. Magnetic resonance
      microscopy showed in some of the CMV43 and Cx43 knockout mice an attenuation of
      the ductus arteriosus, a phenotype which may be indicative of outflow tract
      obstruction. This was confirmed by the in utero Doppler echocardiography, which
      showed increased outflow velocity in E12.5 to 14.5 CMV43 and Cx43 knockout
      fetuses. In some of these fetuses, Doppler analysis also revealed arrhythmia and
      absence of isovolemic contraction time. Further examination of these hearts by
      histology and immunohistochemistry showed abnormal myocardial development in the
      conotruncus. Particularly interesting was the presence of abundant subendocardial
      fibrous tissue expressing smooth muscle actin. In the developing heart, such
      mesenchyme in the outflow tract is usually considered neural crest-derived
      tissue. Together, these results confirm the importance of Cx43 gene dosage in
      conotruncal heart development and suggest that this likely involves a role for
      Cx43 gap junctions in cardiac crest development. In future studies, these
      transgenic mice may serve as valuable animal models for further studying the role
      of gap junctions and cardiac crest cells in conotruncal heart development.

PMID- 9640331
TI  - Roles of secretion and the cytoskeleton in cell adhesion and polarity
      establishment in Pelvetia compressa zygotes.
AB  - During the establishment of polarity, fucoid algal zygotes adhere to the
      substratum and select a growth axis according to environmental cues. Since little
      is known about the early events leading to axis selection, we investigated the
      chronology of cell adhesion, adhesive deposition, and axis selection induced by
      light (photopolarization). The requirements for secretion and the cytoskeleton in
      these processes and in the process of changing the orientation of an axis in
      response to new environmental cues (axis realignment) were also tested. Adhesive
      deposition occurred in two distinct stages: it was deposited uniformally on young
      zygotes (uniform primary adhesive) and later was deposited asymmetrically (polar
      secondary adhesive). Uniform primary adhesive deposition, cell adhesion, and
      photopolarization occurred simultaneously, and shortly thereafter, polar
      secondary adhesive deposition occurred at the future growth site. Uniform primary
      adhesive deposition and cell adhesion required secretion, but were independent of
      filamentous-actin (F-actin) and microtubule function. Photopolarization of young
      zygotes and polar secondary adhesive deposition required secretion but not
      microtubules. F-actin served to localize secondary adhesive deposition at the
      rhizoid pole; its function in polarization was more complex. F-actin was required
      for axis selection; however, its role in realignment of an axis depended on the
      light regime. The differing requirements for F-actin during development indicates
      that the axis is not static, but changes with time. These findings indicate that
      previous and future work on "axis formation" must be interpreted in the context
      of the developmental stage of the zygote.

PMID- 9640332
TI  - Differential dependency of unmyelinated and A delta epidermal and upper dermal
      innervation on neurotrophins, trk receptors, and p75LNGFR.
AB  - The impact of the nerve growth factor (NGF) family of neurotrophins and their
      receptors was examined on the cutaneous innervation in the mystacial pads of
      mice. Ten sets of unmyelinated and thinly myelinated sensory and autonomic
      innervation were evaluated that terminated in the epidermis, upper dermis, and
      upper part of the intervibrissal hair follicles. Mystacial pads were analyzed
      from newborn to 4-week-old mice that had homozygous functional deletions of the
      genes for NGF, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3),
      neurotrophin-4 (NT-4), tyrosine kinase (trk) A, trkB, trkC, or p75. Mystacial
      pads were also analyzed in adult transgenic mice that had overproduction of NGF,
      BDNF, or NT-3 driven by a keratin promoter gene. The innervation was revealed by
      using immunofluorescence and immunocytochemistry with antibodies for protein gene
      product (PGP) 9.5, calcitonin gene-related product (CGRP), substance P (SP),
      galanin (GAL), neuropeptide Y (NPY), tyrosine hydroxylase (TH), and a
      neurofilament protein. The cumulative results indicated that NGF/trkA signaling
      plays a major role in the outgrowth and proliferation of sensory axons, whereas
      NT-3/ trkA signaling plays a major role in the formation of sensory endings. TrkC
      is also essential for the development of three sets of trkA-dependent sensory
      innervation that coexpress CGRP, SP, and GAL. Another set of sensory innervation
      that only coexpressed CGRP and SP was solely dependent upon NGF and trkA.
      Surprisingly, most sets of trkA-dependent sensory innervation are suppressed by
      trkB perhaps interacting with p75. BDNF and NT-4 appear to mediate this
      suppressing effect in the upper dermis and NT-4 in the epidermis. In contrast to
      sensory innervation, sympathetic innervation to the necks of intervibrissal hair
      follicles depends upon NGF/trkA signaling interacting with p75 for both the axon
      outgrowth and ending formation. Although NT-3/trkA signaling is essential for the
      full complement of sympathetic neurons, NT-3 is detrimental to the formation of
      sympathetic terminations to the necks of hair follicles. TrkB signaling mediated
      by BDNF but not NT-4 also suppresses these sympathetic terminations. One sparse
      set of innervation, perhaps parasympathetic, terminating at the necks of hair
      follicles is dependent solely upon NT-3 and trkC. Taken together, our results
      indicate that the innervation of the epidermis, upper dermis, and the upper
      portion of hair follicles is regulated by a competitive balance between promoting
      and suppressing effects of the various neurotrophins.

PMID- 9640333
TI  - Stability and plasticity of neural crest patterning and branchial arch Hox code
      after extensive cephalic crest rotation.
AB  - The extent to which the spatial organisation of craniofacial development is due
      to intrinsic properties of the neural crest is at present unclear. There is some
      experimental evidence supporting the concept of a prepattern established within
      crest while contiguous with the neural plate. In experiments in which the neural
      tube and premigratory crest are relocated within the branchial region, crest
      cells retain patterns of gene expression appropriate for their position of origin
      after migration into the branchial arches, resulting in skeletal abnormalities.
      But in apparent conflict with these findings, when crest is rerouted by late
      deletion of adjacent crest, infilling crest alters its pattern of gene expression
      to match its new location, and a normal facial skeleton results. In order to
      reconcile these findings thus identify processes of relevance to the course of
      normal development, we have performed a series of neural tube and crest rotations
      producing a more extensive reorganisation of cephalic crest than has been
      previously described. Lineage analysis using DiI labelling of crest derived from
      the rotated hindbrain reveals that crest does not migrate into the branchial arch
      it would have colonised in normal development, rather it simply populates the
      nearest available branchial arches. We also find that crest adjacent to the
      grafted region contributes to a greater number of branchial arches than it would
      in normal development, resulting in branchial arches containing mixed cell
      populations not occurring in normal development. We find that after exchange of
      first and third arch crest by rotation of r1-7, crest alters its expression of
      hoxa-2 and hoxa-3 to match its new location within the embryo resulting in the
      reestablishment of the normal branchial arch Hox code. A facial skeleton in which
      all the normal components are present, with some additional ectopic first arch
      structures, is formed in this situation. In contrast, when second and third arch
      crest are exchanged by rotation of r3 to 7, ectopic Hox gene expression is
      stable, resulting in the persistence of an abnormal branchial arch Hox code and
      extensive defects in the hyoid skeleton. We suggest that the intrinsic properties
      of crest have an effect on the spatial organisation of structures derived from
      the branchial arches, but that exposure to increasingly novel environments within
      the branchial region or "community effects" within mixed populations of cells can
      result in alterations to crest Hox code and morphogenetic fate. In both classes
      of operation we find that there is a tight link between the resulting branchial
      arch Hox code and a particular skeletal morphology.

PMID- 9640334
TI  - FGF is an essential regulator of the fifth cell division in preimplantation mouse
      embryos.
AB  - Fibroblast growth factor (FGF) signaling is required prior to gastrulation in the
      mouse embryo. To test for the spatial and temporal requirements of FGF signaling,
      a dominant negative FGF receptor (dnFGFR) was used to make transgenic mouse
      embryos. In mosaic embryos, cell division ceased at the fifth cell division in
      all cells that expressed the mutant receptor, but cell death did not increase.
      After the fifth cell division, the progeny of unaltered cells and cells
      expressing lacZ continued to accumulate at the same rate, suggesting that the FGF
      requirement is cell autonomous. In mosaic embryos, lacZ, but not dnFGFR
      expression was detected in mitotic trophoblasts adjacent to the ICM. Conversely,
      dnFGFR-expressing extraembryonic ectoderm cells were detected at the abembryonic
      pole in postmitotic cells. In blastocysts expressing the dnFGFR in all cells, the
      morphology appeared normal and inner cell masses (ICMs) formed, but resultant
      embryos had only one-third the number of cells as control embryos. In these
      blastocysts, cell division had also ceased at the fifth cell division, but
      cavitation, a concurrent morphogenetic event, initiated and progressed normally.
      To test for the continuing requirement of FGF, FGFR-3 was overexpressed in all
      cells and resulted in an increase in cell numbers after the fifth cell cycle. In
      a model for postimplantation development, addition of FGF-4 to blastocyst
      outgrowths increased the number of extraembryonic ectoderm cells, suggesting a
      continuing role for FGF. Thus, FGF signaling induces the cell division of
      embryonic and extraembryonic cells in the preimplantation mouse embryo starting
      at the fifth cell division. The signal requirement for FGF is cell autonomous,
      but is not required to prevent cell death. This provides the first evidence for
      the necessity of a growth factor before implantation.

PMID- 9640335
TI  - Evidence that Gq family G proteins do not function in mouse egg activation at
      fertilization.
AB  - Embryonic development is initiated after the fertilizing sperm contacts the egg
      and triggers a process termed "egg activation," resulting in calcium release,
      cortical granule exocytosis, recruitment of maternal mRNAs, and cell cycle
      resumption. Heterotrimeric guanine nucleotide-binding proteins (G proteins) may
      be involved in mouse egg activation since inhibition of G protein beta gamma
      subunits partially inhibits sperm-induced cell cycle resumption. In addition,
      specific events of egg activation can be initiated in the absence of sperm by
      acetylcholine stimulation of mouse eggs overexpressing the human m1 muscarinic
      receptor, a G protein-coupled receptor. In somatic cell, G proteins in the Gq
      family couple ligand stimulation of the m1 muscarinic receptor to activation of
      phospholipase C, resulting in the production of inositol 1,4,5-trisphosphate
      (IP3) and IP3-mediated release of intracellular calcium. Since IP3-mediated
      calcium release is involved in egg activation at fertilization, we have examined
      the role of Gq family G proteins in both sperm-independent (muscarinic receptor
      mediated) and sperm-induced egg activation using a function-blocking antibody
      raised against the common C-terminal region of Gq and G11 proteins. We show that
      this antibody effectively inhibits Gq family G proteins in mouse eggs by
      demonstrating that the antibody inhibits egg activation in response to
      stimulation of the m1 muscarinic receptor. This same antibody, however, does not
      inhibit sperm-induced egg activation events. These results indicate that although
      activation of Gq family G proteins can result in egg activation in the mouse, it
      is unlikely that these proteins are used by the sperm to initiate egg activation
      at fertilization.

PMID- 9640336
TI  - Syncope and sudden death in hypertrophic cardiomyopathy.

PMID- 9640337
TI  - Preventing adult disease: windows of opportunity.

PMID- 9640338
TI  - Reflex responses of venous capacitance vessels in patients with hypertrophic
      cardiomyopathy.
AB  - 1. The aim of this study was to determine if there is impaired reflex
      venoconstriction in patients with hypertrophic cardiomyopathy and whether this is
      related to a history of syncope or exercise hypotension. 2. Thirty percent of
      patients with hypertrophic cardiomyopathy have exercise-induced hypotension
      associated with a failure of arteriolar constriction. Impaired venoconstriction
      could exacerbate this situation. 3. We evaluated 43 patients with hypertrophic
      cardiomyopathy and 24 controls. Nuclear venous plethysmography was used to
      measure forearm venous capacitance during lower body negative pressure, splenic
      venous volume changes during bicycle exercise and blood pressure responses to
      treadmill exercise. We assessed any association between abnormal reflex venous
      control and a history of syncope and exercise hypotension. 4. The percentage
      reduction in unstressed forearm venous volume during lower body negative pressure
      was similar in patients and controls (8.9 +/- 7.1% versus 9.7 +/- 5.9%, P not
      significant). Patients with a history of syncope demonstrated a less marked
      percentage reduction in volume than those without (-2.1 +/- 6.9% versus -10.6 +/-
      6.0%, P = 0.001). In three patients with a history of syncope there was a
      paradoxical increase in forearm venous volume during lower body negative
      pressure. During exercise there was a substantially smaller decrease in splenic
      venous volume in patients compared with controls (-20.1 +/- 14.0% and -42.6 +/-
      12.6% respectively, P = 0.0001). Furthermore, there was an association between
      attenuated splenic venoconstriction or venodilation and exercise hypotension in
      patients (P = 0.005). 5. Abnormal reflex control of venous capacitance beds in
      patients with hypertrophic cardiomyopathy was associated with both syncope and
      exercise hypotension.

PMID- 9640339
TI  - Dynamics of circulatory adjustments to head-up tilt and tilt-back in healthy and
      sympathetically denervated subjects.
AB  - 1. The initial circulatory adjustments induced by head-up tilt and tilt-back were
      investigated in six healthy subject (aged 30-58 years) and six patients with
      orthostatic hypotension due to pure autonomic failure (aged 33-65 years). 2.
      Continuous responses of finger arterial pressure and heart rate were recorded by
      Finapres. A pulse contour algorithm applied to the arterial pressure waveform was
      used to compute stroke volume responses. 3. In the healthy subjects, head-up tilt
      induced gradual circulatory adjustments. After 1 min upright stroke volume and
      cardiac output had decreased by 39 +/- 9% and 26 +/- 10% respectively. Little
      change in mean blood pressure at heart level (+1 +/- 7 mmHg) indicated that
      systemic vascular resistance had increased by 39 +/- 24%. The gradual responses
      to head-up tilt contrasted with the pronounced and rapid circulatory responses
      upon tiltback. After 2-3 s a rapid increase in stroke volume (from 62 +/- 8% to
      106 +/- 10%) and cardiac output (from 81 +/- 11% to 118 +/- 20%) was observed
      with an overshoot of mean arterial pressure above supine control values of 16 +/-
      3 mmHg at 7 s. In the patients a progressive fall in blood pressure on head-up
      tilt was observed. After 1 min upright mean blood pressure had decreased by 59 +/
      8 mmHg. No change in systemic vascular resistance and a larger decrease in
      stroke volume (60 +/- 7%) and cardiac output (53 +/- 8%) were found. On tilt-back
      a gradual recovery of blood pressure was observed. 4. In healthy humans upon head
      up tilt neural compensatory mechanisms are very effective in maintaining arterial
      pressure at heart level. The gradual circulatory adjustments to head-up tilt in
      healthy subjects contrast with the pronounced and abrupt circulatory changes on
      tilt-back. In patients with a lack of neural circulatory reflex adjustments,
      gradual blood pressure decreases to head-up tilt and gradual increases to tilt
      back are observed.

PMID- 9640340
TI  - Cerebral blood flow velocity during and after sustained isometric skeletal muscle
      contractions in man.
AB  - 1. Twenty-seven young subjects used their right hand to perform sustained,
      isometric contractions at 40% of maximum for 2 min while lying supine. 2. During
      the last 30 s of exercise, mean arterial blood pressure increased by 38 +/- 4
      mmHg (mean +/- S.E.M.) and heart rate by 27 +/- 2 beats/min. 3. Nineteen of the
      subjects respired eucapnically during exercise, increasing ventilation by 4.1 +/-
      0.5 litres/min. Eight subjects hyperventilated (7.1-19.6 litres/min) and
      decreased end-tidal PCO2 by 8.2 to 15.1 mmHg during the last minute of exercise.
      4. In the eucapnic subjects mean flow velocity in the right (i.e. contralateral
      to the activated cortex) middle cerebral artery increased by 11.4 +/- 1.0 cm/s, a
      change of 17%, during the contraction. This represents an increase in volume flow
      to the territory of this vessel, but an increase in global flow to the brain
      cannot be inferred. 5. In the eight subjects who hyperventilated during exercise,
      there was no rise of flow velocity in the middle cerebral artery, and in some
      subjects there was a fall during the first 2 min of recovery. These findings
      suggest that if subjects hyperventilate during handgrip exercise there could be a
      fall in volume flow to many regions of the brain during and after the exercise.

PMID- 9640341
TI  - Differential regulation of ventricular adrenomedullin and atrial natriuretic
      peptide gene expression in pressure and volume overload in the rat.
AB  - 1. Adrenomedullin is a recently discovered vasodilating and natriuretic peptide
      whose physiological and pathophysiological roles remain to be established. Like
      atrial natiuretic peptide adrenomedullin is expressed in the left ventricle.
      Ventricular expression of atrial natriuretic peptide is known to be markedly
      increased by volume or pressure overload. In this study we investigated whether
      ventricular expression of adrenomedullin is similarly stimulated under such
      conditions. 2. Ventricular adrenomedullin and atrial natriuretic peptide mRNA
      levels as well as those of a loading control mRNA (glyceraldehyde-3-phosphate
      dehydrogenase) were quantified by Northern blot analysis in (a) rats with severe
      post-infarction heart failure induced by left coronary ligation at 30 days post
      surgery and (b) in rats with pressure-related cardiac hypertrophy induced by
      aortic banding at several time points (0.5, 1 and 4 h, and 1, 4, 7 and 28 days)
      after surgery. Levels were compared with those in matched sham-operated controls.
      3. The mRNA level of atrial natriuretic peptide was markedly increased (8-10
      fold) in the left ventricle of animals with post-infarction heart failure. In
      contrast, there was only a modest (40%) increase in the level of adrenomedullin
      mRNA. In rats with pressure-induced cardiac hypertrophy the ventricular level of
      atrial natriuretic peptide mRNA was again markedly increased (maximum 10-fold).
      The increase was first noticeable at 24 h post-banding and persisted until 28
      days. In contrast, there was no change in adrenomedullin mRNA level compared with
      sham-operated rats at any time point. 4. Despite having similar systemic effects,
      the expression of adrenomedullin and atrial natriuretic peptide in the left
      ventricle is differently regulated. The findings imply distinct roles for the two
      peptides. The results do not support an important role for ventricular
      adrenomedullin expression in the remodelling process that occurs during the
      development of cardiac hypertrophy but suggest that ventricular adrenomedullin
      participates in the local and/or systemic response to heart failure.

PMID- 9640342
TI  - Chronic administration of octreotide ameliorates portal hypertension and portal
      hypertensive gastropathy in rats with cirrhosis.
AB  - 1. Portal hypertension and hyperdynamic circulation have been postulated to play
      a role in the pathogenesis of portal hypertensive gastropathy. Administration of
      octreotide to portal hypertensive rats has been shown to reduce portal pressure
      and ameliorate hyperdynamic circulation. 2. This study investigated the effects
      of chronic administration of octreotide on systemic and portal haemodynamics and
      the development of portal hypertensive gastropathy in carbon tetrachloride
      induced cirrhotic rats. 3. After 12 weeks of carbon tetrachloride induction,
      cirrhotic rats were randomly assigned to receive either placebo (5% dextrose in
      water) or octreotide (65 micrograms/kg in 5% dextrose in water) subcutaneously
      twice daily for 10 days. Haemodynamic studies with a thermodilution technique and
      gastric morphometric analyses were performed at 10 days after treatment. 4. In
      cirrhotic rats, octreotide treatment induced a significant increase in systemic
      vascular resistance (2.7 +/- 0.2 versus 3.4 +/- 0.2 mmHg/ml.min-1.100 g-1, P <
      0.05) and decrease in portal pressure (12.5 +/- 1.2 versus 9.9 +/- 0.5 mmHg, P <
      0.05) compared with placebo-treated rats. In addition, octreotide treatment
      significantly reduced the mean cross-sectional area of gastric mucosal vessels
      (2290 +/- 145 versus 1810 +/- 101 micron 2, P < 0.05). 5. This study shows that
      chronic octreotide treatment ameliorates the development of portal hypertensive
      gastropathy in cirrhotic rats. The effect of octreotide on portal hypertensive
      gastropathy may, at least partly, be due to the alleviation of portal
      hypertension and hyperdynamic circulation.

PMID- 9640343
TI  - Early administration of angiotensin-converting enzyme inhibitor captopril,
      prevents the development of hypertension programmed by intrauterine exposure to a
      maternal low-protein diet in the rat.
AB  - 1. Associations of intrauterine exposure to maternal undernutrition with later
      hypertension and coronary heart disease in the human population have been
      duplicated in the rat. Fetal exposure to low protein diets produces offspring
      that develop raised systolic blood pressure by the age of weaning. This animal
      model of 'programmed' hypertension was used to investigate the role of the renin
      angiotensin system in the initiation and maintenance of high blood pressure. 2.
      Pregnant rats were fed diets containing 18 or 9% casein from conception until
      littering. The offspring from these pregnancies were administered captopril
      either between 2 and 4 weeks of age, or from 10 to 12 weeks of age. 3. The
      feeding of low protein diets in pregnancy had no effect upon the reproductive
      ability of female rats and the offspring generated were of normal birthweight. By
      4 weeks of age the male and female offspring of low-protein-fed dams had systolic
      blood pressures that were 24-25 mmHg higher than those of rats exposed to a
      control diet in utero. 4. Treatment of 10-week-old female offspring with
      captopril for 2 weeks indicated that angiotensin II formation may play a role in
      the maintenance of high blood pressure in low-protein-exposed rats. While
      captopril had no significant effect upon systolic pressures of rats exposed to
      the control diet in intrauterine life, the systolic blood pressures of low
      protein animals rapidly declined by 31 mmHg. 5. Administration of captopril to
      male and female offspring between 2 and 4 weeks of age exerted long-term effects
      upon systolic blood pressure. Eight weeks after cessation of treatment, at an age
      where maximal blood pressures are achieved, captopril-treated, low-protein
      exposed rats had similar blood pressures to normotensive rats exposed to the
      protein-replete diet in utero. 6. In conclusion, we have demonstrated that the
      elevation of adult blood pressure associated with fetal exposure to a maternal
      low-protein diet, is prevented by early administration of an angiotensin
      converting enzyme inhibitor. The actions of angiotensin II in the late suckling
      period may be a critical determinant of long-term cardiovascular functions in
      these animals.

PMID- 9640344
TI  - Human muscle sympathetic activity and cardiac catecholamine spillover: no support
      for augmented sympathetic noradrenaline release by adrenaline co-transmission.
AB  - 1. Evidence from animal studies indicates that circulating adrenaline may be
      taken up into sympathetic nerves, facilitating the release of noradrenaline. To
      test whether adrenaline acts as a co-transmitter in humans we studied eight
      healthy men (aged 19-23 years) during isometric handgrip before and after an
      adrenaline infusion (1-3 micrograms/min for > 30 min). Sympathetic activity was
      assessed using radiotracer kinetic techniques to measure total and cardiac
      spillovers of noradrenaline and adrenaline, and microneurography to measure
      muscle sympathetic activity. 2. During the adrenaline infusion systolic blood
      pressure and heart rate increased significantly and diastolic blood pressure
      decreased. Total noradrenaline spillover, and arterial and coronary sinus plasma
      noradrenaline concentrations, increased significantly. Muscle sympathetic nerve
      traffic increased both during and after the end of the infusion. 3. Thirty
      minutes after the end of the adrenaline infusion there was adrenaline release
      from the heart (1.5 +/- 0.4 ng/min, mean +/- S.E.M.) indicating that significant
      adrenaline loading of cardiac sympathetic nerves had occurred. At this time
      muscle sympathetic nerve traffic and total body and cardiac noradrenaline
      spillovers were similar (P > 0.05) to pre-adrenaline infusion values (nerve
      traffic 24 +/- 4 versus 21 +/- 3 bursts/min; total noradrenaline spillover 698 +/
      98 versus 618 +/- 119 ng/min; cardiac noradrenaline spillover 16.2 +/- 2.8
      versus 13.9 +/- 3.9 ng/min). 4. Isometric handgrip contraction evoked similar
      responses pre- and post-adrenaline infusion in total and cardiac noradrenaline
      spillovers and in muscle sympathetic activity. 5. The results do not support the
      theory that adrenaline is a co-transmitter facilitating noradrenaline release
      from human sympathetic nerves.

PMID- 9640345
TI  - Vascular endothelial growth factor (VEGF) is released from platelets during blood
      clotting: implications for measurement of circulating VEGF levels in clinical
      disease.
AB  - 1. Dysregulated vascular endothelial growth factor (VEGF) expression has been
      reported in several pathological states based upon evidence of elevated serum
      VEGF levels. Using two immunoassays for VEGF, this study determines normal plasma
      and serum VEGF ranges, determines which are more likely to reflect circulating
      VEGF levels and investigates a potential contribution of VEGF from platelets to
      VEGF levels detected in serum. 2. The presence of soluble VEGF receptor, sflt-1,
      at a molar excess of 7:1 significantly reduced measured VEGF levels in both
      assays. Serum VEGF levels were higher than plasma levels in children [(mean +/-
      S.E.M.) 306.1 +/- 39.4 versus 107.4 +/- 24.9 pg/ml, P < 0.0001] and adults (249.4
      +/- 46.4 versus 76.1 +/- 10.7 pg/ml, P < 0.0001). Serum VEGF increased with
      clotting time (P = 0.0005 t0 compared with 2 h samples); plasma VEGF levels were
      not affected by time between sampling and centrifugation. 3. Calcium-induced
      clotting of platelet-rich but not platelet-poor plasma induced VEGF release with
      a proportional response between platelet count and VEGF level and isolated
      platelets released significant quantities of VEGF upon incubation with thrombin.
      Reverse transcriptase-PCR studies confirmed that platelets express VEGF121 and
      VEGF165 mRNA. 4. These data suggest that plasma is the preferred medium to
      measure VEGF levels; a significant and highly variable platelet-mediated
      secretion of VEGF during the clotting process invalidates the use of serum as an
      indicator of circulating VEGF levels in disease states.

PMID- 9640346
TI  - Bone mineral changes during pregnancy and lactation: a longitudinal cohort study.
AB  - 1. The influence of pregnancy, lactation and weaning on bone mineral density in
      healthy women was investigated during a 2 year prospective study of 59 pregnant
      and lactating women from the 18th week of gestation. 2. Bone mineral density was
      measured by dual energy X-ray absorptiometry at the non-dominant radius ultra
      distally and more proximally in the 18th and 37th weeks of gestation, and 0, 3,
      6, 12 and 18 months after delivery. Measurements of bone mineral density of the
      lumbar spine, the proximal femur and the whole body were performed at all dates
      after delivery. 3. Reappearance of menstruation after delivery averaged 6.1
      months; mean lactating period was 8.7 months. During pregnancy and lactation bone
      mineral density tended to decrease, but different measuring sites showed
      different patterns of bone mineral density changes. The reduction in the ultra
      distal radius during pregnancy amounted to 2%, and no further changes were
      observed here during lactation. After delivery, reduction in mean bone mineral
      density was most pronounced in the spine (5.2% in 3 months), but the fall in bone
      mass tended to revert after resumption of menstruation. Bone mineral density was
      still reduced by 3.3% after 12 months in women with menstruation resumption later
      than 8 months after delivery. No significant reduction was observed 18 months
      after delivery. No association with calcium intake, weight changes or initial
      bone mineral density was observed. High calcium intake did not protect against
      bone mineral loss in the spine and the femur. 4. Thus it can be concluded that
      bone loss during pregnancy and lactation took place mainly from the trabecular
      skeleton. Resumption of menstruation tended to result in a regain of bone mass
      towards baseline.

PMID- 9640347
TI  - Sustained modifications of protein metabolism in various tissues in a rat model
      of long-lasting sepsis.
AB  - 1. Sepsis was induced in rats by an intravenous injection of live bacteria.
      Infected and pair-fed animals were studied before the infection, in an acute
      septic phase (day 2 post-infection), in a chronic septic phase (day 6) and in a
      late septic phase (day 10). Protein synthesis rates were measured in vivo after
      administration of a flooding dose of L[1-13C]valine. 2. During the acute phase,
      muscle protein loss associated with infection resulted from both a decrease in
      protein synthesis and an increase in proteolysis. During the chronic phase and
      the late phase, the increase of proteolysis in infected rats as compared with
      pair-fed animals persisted, worsening muscle atrophy. Skin protein synthesis
      rates were not significantly modified by infection. However, skin protein content
      decreased 6 and 10 days after infection, suggesting an increased proteolysis in
      response to sepsis. 3. Protein synthesis in liver of infected rats was twice that
      of pair-fed animals. Liver protein synthesis remained elevated in infected rats
      compared with pair-fed animals until day 10. Hypoalbuminaemia and high plasma
      concentrations of fibrinogen were evident at all periods studied. alpha 2
      Macroglobulin and alpha 1-acid glycoprotein reached peak concentrations during
      the acute phase (concentrations increased 50 times in infected rats). On day 10,
      the levels of these proteins were still about 12-fold higher. 4. Protein
      synthesis rates were significantly increased in the digestive tract and lung of
      infected rats compared with pair-fed groups on days 2 and 6, but were similar in
      the two groups on day 10 post-infection. The fractional protein synthesis rate
      was increased 3-fold over the entire experimental period in the spleen. 5. The
      results show that sepsis stimulates protein synthesis in various tissues over a
      long time, and that skin, like muscle, can provide amino acids to the rest of the
      body.

PMID- 9640348
TI  - Proximal renal tubular peptide catabolism, ammonia excretion and tubular injury
      in patients with proteinuria: before and after lisinopril.
AB  - 1. Progression to renal failure may be linked to the degree of proteinuria
      through tubulo-interstitial mechanisms. However, there are no data in man on the
      kinetics of proximal renal tubular protein catabolism or markers of tubular
      injury before and after lisinopril. We developed a method to allow such studies,
      and found increased tubular catabolism of 99mTc-labelled aprotinin (Trasylol) in
      patients with nephrotic range proteinuria which was associated with increased
      ammonia excretion. 2. In this study, 10 patients with mild renal impairment (51Cr
      EDTA clearance 63.7 +/- 8.3 ml.min-1.1.73 m-2) and heavy proteinuria (8.2 +/- 2.3
      g/ 24 h) were given lisinopril (10-20 mg) for 6 weeks. Renal tubular catabolism
      of intravenous aprotinin was measured before and after lisinopril by renal
      imaging and urinary excretion of the free radiolabel over 26 h. Fractional
      degradation was calculated from these data. Fresh timed urine collections were
      also analysed for ammonia excretion every fortnight from 6 weeks before
      treatment. Total urinary N-acetyl-beta-D-glucosaminidase and the more tubulo
      specific N-acetyl-beta-D-glucosaminidase 'A2' isoenzyme were also measured. 3.
      After lisinopril proteinuria fell significantly as expected (from 9.5 +/- 1.6 to
      4.5 +/- 1.0 g/24 h, P < 0.01). This was associated with a reduction in metabolism
      over 26 h (from 1.7 +/- 0.1 to 1.2 +/- 0.1% dose/h, P < 0.01) and in fractional
      degradation of aprotinin (from 0.08 +/- 0.02 to 0.04 +/- 0.007/h, P < 0.04).
      Ammonia excretion also fell significantly (from 1.2 +/- 0.1 to 0.6 +/- 0.1
      mmol/h, P < 0.0001), as did both total urinary N-acetyl-beta-D-glucosaminidase (P
      < 0.0001) and the N-acetyl-beta-D-glucosaminidase 'A2' isoenzyme (P < 0.015).
      These observations after lisinopril treatment have not been described previously.
      There was no significant change in blood pressure nor in glomerular
      haemodynamics.

PMID- 9640349
TI  - Inappropriately high plasma leptin levels in obese haemodialysis patients can be
      reduced by high flux haemodialysis and haemodiafiltration.
AB  - 1. Blood leptin levels are increased in obese subjects and seem to play a major
      role in the hypothalamic regulation of appetite and energy expenditure. 2. We
      measured plasma leptin levels in a cohort of 46 patients on maintenance
      haemodialysis treatment and 26 control subjects. 3. Higher body mass indices were
      associated with higher plasma leptin levels in both groups. 4. The increase was
      more pronounced in the dialysis group than in the control group (P = 0.001),
      leading to inappropriately high plasma levels. 5. Haemodialysis with low flux
      cellulosic dialysers did not result in a decrease in plasma levels, while
      dialysis with high flux dialysers and haemodiafiltration led to a substantial
      reduction of the initial value to 76.95 +/- 14.89% (P = 0.013) and 62.90 +/-
      24.94% (P = 0.001) respectively. 6. Our data suggest that high flux dialysis
      membranes can decrease plasma leptin levels and that inappropriately high plasma
      leptin levels may play a role in the nutrition of haemodialysis patients.

PMID- 9640350
TI  - Neutrophil cathepsin G modulates platelet P-selectin expression and inhibits P
      selectin-mediated platelet-neutrophil adhesion.
AB  - 1. Close contact between platelets and neutrophils modulates their cellular
      interactions in thrombotic and inflammatory states, with stimulation of P
      selectin expression on platelets by agonists such as thrombin and neutrophil
      derived cathepsin G being critical in mediating platelet-neutrophil adhesion.
      This study compared the effects of thrombin and cathepsin G on platelet P
      selectin expression and on P-selectin-mediated platelet-neutrophil adhesion. 2.
      Washed platelets and platelet-neutrophil mixed cell suspensions
      (platelet/neutrophil ratio, 10:1) were incubated with either the supernatant of
      activated neutrophils, purified cathepsin G or thrombin. Platelet P-selectin
      expression and platelet adhesion to neutrophils was quantified by flow
      fluorocytometric analysis. 3. The supernatant from activated neutrophils
      stimulated platelet P-selectin expression comparable to that produced by purified
      cathepsin G or thrombin. P-selectin expression induced by both activated
      neutrophil supernatant and purified cathepsin G was completely inhibited by alpha
      1-antichymotrypsin, a specific inhibitor of cathepsin G. Unlike thrombin, which
      induced maximum platelet P-selectin expression by 10 min, sustained to 120 min,
      cathepsin G induced an initial large increase in platelet P-selectin expression,
      followed by a progressive reduction over 30-60 min to baseline levels. 4. Co
      incubation of neutrophils with thrombin-stimulated platelets resulted in a
      significant increase in P-selectin-mediated platelet-neutrophil adhesion, which
      was completely inhibited by preincubation of neutrophils with anti-sialyl
      Lewis(x) monoclonal antibody. Thrombin produced maximum platelet-neutrophil
      adhesion by 10 min which remained stable over 120 min. In contrast, cathepsin G
      stimulated platelets did not adhere to neutrophils over 120 min of co-incubation.
      Addition of cathepsin G to thrombin-stimulated platelets caused a progressive
      reduction over 30-60 min to baseline levels of platelet-neutrophil adhesion. 5.
      Neutrophil-derived cathepsin G is a potent platelet activator, but unlike
      thrombin it causes a time-dependent loss of platelet P-selectin expression and
      inhibits P-selectin-mediated platelet-neutrophil adhesion. Therefore, cathepsin G
      may modulate thrombin-mediated platelet-neutrophil adhesive interactions in
      inflammation and thrombosis.

PMID- 9640351
TI  - Effect of oxidative stress on lymphocytes from elderly subjects.
AB  - 1. Oxidative damage has been associated with ageing, but there is no agreement as
      to whether or not it is produced by a decrease in antioxidant defences with the
      ageing process. In purified lymphocytes from 47 healthy elderly (75.27 +/- 0.91
      years) and 47 healthy young (29.87 +/- 0.53 years) volunteers, we studied the
      levels of antioxidant enzyme activity (superoxide dismutase, catalase and
      glutathione peroxidase), protein oxidative damage (as protein carbonyl content)
      and lysosomal proteolytic activity (cathepsins B, H and L), with and without
      exposure to oxidative stress produced by 25 mumol/l H2O2. 2. There were no
      differences in antioxidant enzyme activities in the stressed and non-stressed
      samples between the young and elderly subjects, indicating that there was no
      relationship between age and antioxidant enzyme activity even in oxidative
      stress. However, a dissimilar response to oxidative stress was observed in
      protein oxidative damage and cathepsin B and L activities, depending on the age
      of the donor. 3. With these results we conclude that oxidative stress produces
      greater protein oxidative damage and increased protein degradation in elderly
      subjects than in young ones; this effect cannot be attributed to dissimilar
      antioxidant enzyme responses to oxidative stress, since these did not differ
      between the two age groups.

PMID- 9640352
TI  - Time course and pattern of pulmonary flow distribution following unilateral
      airway occlusion in sheep.
AB  - 1. Unilateral bronchial occlusion causes ipsilateral hypoxic pulmonary
      vasoconstriction, which shifts blood flow towards the other lung. We studied the
      time course of flow diversion following acute bronchial occlusion, and the
      temporal effect of the latter on blood gases and vertical distribution of blood
      flow within the two lungs. 2. Serial infusion of radioactive or fluorescent
      microspheres were given to each of seven adult standing sheep before, during
      occlusion of the left mainstem bronchus for up to 6 min, and after release of
      occlusion. Pulmonary and systemic arterial pressures were recorded continuously
      and arterial and mixed venous blood gases were determined intermittently. Post
      mortem, the lungs were inflated, dried and cut into slices. Relative blood flow
      at the time of infusion was expressed as the weight-normalized intensity of each
      tracer in each slice or lung divided by the weight-normalized intensity in the
      two lungs. 3. Within 30 s, 1 min and 2 min after onset of occlusion, flow in the
      occluded lung had decreased to 68-84% (range), 51-78% and 43-79% respectively, of
      the initial value. In the contralateral lung, flow increased by 10-24%, 14-37%
      and 23-39% respectively. The distribution of flow along the gravitational axis
      within each lung varied widely between animals, both before and during occlusion.
      The during-occlusion profiles in the occluded lung differed from those in the non
      occluded lung. In either lung, during-occlusion profiles could not be predicted
      with certainty from the pre-occlusion profiles. Two minutes post-occlusion, inter
      and intra-lung flow distribution were nearly the same as before occlusion.
      Arterial oxygen tension fell in the first minute of occlusion, but never below
      7.5 kPa, and increased slowly thereafter. Arterial carbon dioxide tension
      increased slightly throughout the occlusion period. No appreciable changes in
      systemic or pulmonary artery pressure were observed. Post-occlusion, arterial
      oxygen tension was still sub-normal, while carbon dioxide tension continued to
      increase. 4. We conclude that acute unilateral bronchial occlusion diverts blood
      flow within 30 s towards the contralateral lung. This rapidly occurring flow
      diversion prevents the development of severe arterial hypoxaemia. The variable
      and largely unpredictable distribution of blood flow in the hyperfused non
      occluded lung might explain some of the gas-exchange abnormalities observed in
      physiologically hyperfused lungs and in patients with one hyperfused lung.

PMID- 9640353
TI  - Benjamin W. Zweifach 1910-1997.

PMID- 9640354
TI  - Linear viscoelastic properties of bovine brain tissue in shear.
AB  - We report the results from a series of rheological tests of fresh bovine brain
      tissue. Using a standard Bohlin VOR shear rheometer, shear relaxation and
      oscillating strain sweep experiments were performed on disks of brain tissue 30
      mm in diameter, with a thickness of 1.5-2 mm. The strain sweep experiment showed
      that the viscoelastic strain limit is of the order of 0.1% strain. Shear
      relaxation data do not indicate the presence of a long-term elastic modulus,
      indicating fluid-like behavior. A relaxation spectrum was calculated by inverting
      the experimental data and used to predict oscillatory response, which agreed well
      with measured data.

PMID- 9640355
TI  - Rheological behavior of rat mesangial cells during swelling in vitro.
AB  - The response of cells to mechanical forces depends on the rheological properties
      of their membranes and cytoplasm. To characterize those properties, mechanical
      and electrical responses to swelling were measured in rat mesangial cells (MC)
      using electrophysiologic and video microscopic techniques. Ion transport rates
      during hyposmotic exposures were measured with whole-cell recording electrodes.
      Results showed that cell swelling varied nonlinearly with positive internal
      pressure, consistent with a viscoelastic cytoplasm. The extrapolated area
      expansivity modulus for small deformations was estimated to be 450 dyne/cm. Cell
      swelling, caused either by positive pipet pressure or hyposmotic exposure (40-60
      mOsm Kg-1), rapidly induced an outwardly rectifying membrane conductance with an
      outward magnitude 4-5 times the baseline conductance of 0.9 +/- 0.5 nS (p < .01).
      Swelling-induced (SI) current was weakly selective for K+ over Na+, partially
      reversed upon return to isotonicity, and was antagonized by 0.5 mM GdCl3 (p <
      0.02; n = 6). Isolated cells treated with GdCl3 rapidly lysed after hypotonic
      exposure, in contrast to untreated cells that exhibited regulatory volume
      decrease (RVD). Our results indicate that volume regulation by MC depends upon a
      large swelling-induced K+ efflux, and suggest that swelling in MC is a
      viscoelastic process, with a viscosity dependent on the degree of swelling.

PMID- 9640356
TI  - Inertial migration based concentration factors for suspensions of Chlorella
      microalgae in branched tubes.
AB  - When a dilute suspension flows in the laminar regime through a tube, under
      certain conditions the suspended particles migrate radially to an equilibrium
      radial position. Branched tubes can use this radial concentration distribution to
      concentrate dilute suspensions. Suspensions of microalgae, Chlorella vulgaris,
      were pumped through tubes of various diameters for tube Reynolds number ranging
      from 47-1839 and photographed. Upstream particle concentration profiles were
      obtained by image analysis of the photographs. The dividing stream surfaces in
      branched tubes were obtained from the three-dimensional numerical solutions of
      the Navier-Stokes equations for steady, laminar, and homogeneous flow through
      tubes having one and two orthogonal branches. Concentration factors for Chlorella
      suspensions in branched tubes, predicted by a general method, fall in the range
      of 1.0-1.3.

PMID- 9640357
TI  - Simulation of red blood cell aggregation in shear flow.
AB  - A simulation model has been developed for red blood cell (RBC) aggregation in
      shear flow. It is based on a description of the collision rates of RBC, the
      probability of particles sticking together, and the breakage of aggregates by
      shear forces. The influence of shear rate, hematocrit, aggregate fractal
      dimension, and binding strength on aggregation kinetics were investigated and
      compared to other theoretical and experimental results. The model was used to
      simulate blood flow in a long large diameter tube under steady flow conditions at
      low Reynolds numbers. The time and spatial distribution of the state of
      aggregation are shown to be in qualitative agreement with previous B-mode
      ultrasound studies in which a central region of low echogenicity was noted. It is
      suggested that the model can provide a basis for interpreting prior measurements
      of ultrasound echogenicity and may help relate them to the local state of
      aggregation.

PMID- 9640358
TI  - Ultrasound backscattering from non-aggregating and aggregating erythrocytes--a
      review.
AB  - The objective of the present paper is to provide a detailed review of
      theoretical, experimental and clinical works aimed at understanding the
      scattering of ultrasound by red blood cells (RBC). The paper focuses on the role
      of biofluid mechanics and blood biorheology on the scattering mechanisms. The
      influence of RBC aggregation on the ultrasound backscattered power is
      specifically addressed. After a short introduction, the paper presents the theory
      of Rayleigh scattering and summarizes theoretical models on ultrasound
      backscattering by RBC. The particle, continuum and hybrid models are presented
      along with reported packing factors used to consider the orderliness in the
      spatial arrangement of RBC. Computer models of ultrasound backscattering by RBC
      are also presented in this section. In the second section, experimental factors
      affecting the ultrasound backscattered power from blood are presented. The
      influence of the volume of the scatterers, ultrasound frequency, hematocrit,
      orientation of the scatterers, flow turbulence, flow pulsatility, and
      concentration of fibrinogen and dextran is discussed. The third section focuses
      on the use of ultrasound to characterize RBC aggregation. Three aspects are
      reported: the shear rate dependence of the backscattered power, the "black hole"
      phenomenon, and the kinetics of RBC rouleau formation. The fourth section reports
      in vivo observations of the "smoke like" echo in mitral valve disease, and blood
      echogenicity and backscattered power in veins and arteries. In the last section,
      new areas of research, clinical applications of ultrasound backscattering, and
      areas of potential future developments are presented.

PMID- 9640359
TI  - Vulval lichen planus.
AB  - Lichen planus of the vulva can occur as part of more widespread disease or in
      isolation. Its cause is unknown, but it can become chronic and has a potential
      for malignant change. It may present a difficult management problem and several
      treatments have been used with variable success. This review focuses on the
      problem of vulval lichen planus, and highlights some of the treatments and
      management strategies that have been used to date.

PMID- 9640360
TI  - Identification of common dermatophytes (Trichophyton, Microsporum,
      Epidermophyton) using polymerase chain reactions.
AB  - Polymerase chain reaction (PCR) fingerprinting detected DNA polymorphisms among
      frequently isolated species and strains of the genera Trichophyton, Microsporum
      and Epidermophyton. The patterns generated by this DNA-based method permitted
      species and strains to be identified. The conventional methods to identify
      dermatophytes rely on the expression of characteristic morphological features, as
      well as several physiological properties. Identification is often delayed or
      problematic because isolates may be slow to form conidia or produce atypical
      microscopic structures or colony appearances. Using non-specific primers such as
      (AC)10, (GTG)5, M13 core sequence and AP3, characteristic PCR profiles were
      generated for 17 species. Intraspecies variables were also observed for four of
      six varieties of T. mentagrophytes, whereas no detectable DNA variability was
      found within the three varieties of T. tonsurans. Comparing species-specific PCR
      fingerprints of clinical isolates with those of type strains, species could be
      identified by their PCR fingerprints, even if they could not be identified by the
      accepted phenotypic characteristics.

PMID- 9640361
TI  - Non-uniform cellular packing of the stratum corneum and permeability barrier
      function of intact skin: a high-resolution confocal laser scanning microscopy
      study using highly deformable vesicles (Transfersomes).
AB  - Novel, functional skin staining with fluorescent, ultradeformable lipid vesicles
      (Transfersomes, IDEA, Munich, Germany) was developed and combined with confocal
      laser scanning microscopy. This revealed the structural and barrier
      characteristics of intact skin to a resolution of > or = 0.2 micron, that is, to
      the limit of light microscopy. Different routes of penetration into the stratum
      corneum were visualized and new details in the skin anatomy and barrier were
      unveiled. Most prominent was the lateral inhomogeneity of the stratum corneum,
      where three to 10 neighbouring corneocyte 'columns' were found to form a cluster.
      Corneocyte edges inside each cluster intercalated extensively, but adjacent
      clusters were separated by 'gorges' a few micrometers deep; lipid packing was
      also less regular and tight in the intercluster region. Two quantitatively
      different hydrophilic pathways were found in the horny layer: an intercluster
      route with low penetration resistance comprising < or = 1% of the total or < or =
      20% of the pathway area in the skin, and an intercorneocyte pathway that resists
      penetration better and is more abundant (> or = 3% of the skin or > or = 80% of
      the pathway area). This latter route is strongly tortuous, as it goes between all
      the corneocytes in a cluster. It traces the irregularities between the
      intercellular lipid lamellae and/or the adjacent corneocyte envelopes which may
      act as virtual channels in the skin. It was inferred that such channels coincide
      with the route of water evaporation through the skin and exhibit the permeability
      barrier maximum in the stratum corneum conjunctum.

PMID- 9640362
TI  - Application of confocal laser scanning microscopy to differential diagnosis of
      bullous pemphigoid and epidermolysis bullosa acquisita.
AB  - We applied confocal laser scanning microscopy to fluorescence overlay antigen
      mapping (FOAM) for differential diagnosis of bullous pemphigoid (BP) and
      epidermolysis bullosa acquisita (EBA). FOAM of tissue-bound IgG and marker
      basement membrane components (BMCs) including integrin beta 4, laminin-1, laminin
      5 and type IV collagen, showed that tissue-bound IgG in perilesional skin samples
      from five patients with BP was localized on the epidermal side of type IV
      collagen, and colocalized with some of the other three BMCs, whereas IgG in a
      sample from a patient with EBA was on the dermal side of all the BMCs. FOAM of
      binding sites of autoantibodies in patients' sera and markers including integrin
      beta 4, laminin-1, type IV collagen and type VII collagen, showed that the
      binding sites of autoantibodies from 16 patients with BP were localized on the
      epidermal side of type IV and type VII collagens, and localized above or
      codistributed with integrin beta 4 and laminin-1, whereas those from five
      patients with EBA were codistributed with type IV and type VII collagens, and
      localized on the dermal side of integrin beta 4 and laminin-1. These spatial
      relationships are compatible with their previously described ultrastructural
      locations. Thus, this method appears to be useful in the differential diagnosis
      of BP and EBA.

PMID- 9640363
TI  - Mucous membrane pemphigoid: a dual circulating antibody response with IgG and IgA
      signifies a more severe and persistent disease.
AB  - Mucous membrane pemphigoid (MMP) is an autoimmune blistering disease frequently
      associated with scarring of involved clinical sites. At present, therapeutic
      intervention in the form of immunomodulating or immunosuppressive agents is often
      reserved until the onset of significant inflammation and/or early cicatrization.
      We have therefore studied the clinical and immunopathological findings in 67
      patients with MMP in order to try to establish a reliable prognostic indicator by
      which patients at high risk may be identified early in the disease. Inclusion
      criteria were a predominantly mucosal disease and the detection of IgG and/or C3
      anti-basement membrane zone (BMZ) immunoreactants using immunofluorescence
      techniques. Patients were allocated to three disease subgroups on the basis of
      the modality and duration of therapeutic intervention required to achieve
      effective control of disease. In addition, at presentation and at each follow-up
      visit, a clinical score for severity of involved clinical sites was awarded and
      serum collected for indirect immunofluorescence (IIF). A dual circulating anti
      basement membrane zone (anti-BMZ) antibody response with IgG and IgA was
      significantly associated with a more severe and persistent disease profile (P <
      0.001). The odds ratios for requiring systemic therapy were: 11.6 among patients
      in whom there was a clinical score > or = 5 compared with a score < 5, and 31.3
      and 66.9 among patients with IgG alone and both IgG and IgA, respectively,
      compared with negative IIF. The findings suggest that an assessment based upon a
      combination of site severity score and the presence of circulating IgG and IgA by
      IIF using 1 mol/L salt-split human skin substrate may be considered a useful
      prognostic indicator.

PMID- 9640364
TI  - Cytokine pattern in blister fluid and serum of patients with bullous pemphigoid:
      relationships with disease intensity.
AB  - Few and contrasting data are available in the literature concerning the levels of
      various cytokines in blister fluid (BF) and in the serum of patients affected
      with bullous pemphigoid (BP). Using commercially available ELISA kits, this study
      reports the levels of 11 cytokines detected both in BF and sera of 15 BP patients
      and compares them with those of 15 control subjects' sera. Generally, no
      significant differences were observed in BP and control sera. In contrast,
      interleukin (IL) 1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, tumour necrosis factor
      alpha (TNF-alpha) and interferon-gamma (IFN-gamma) showed increased BF levels as
      compared with BP sera. Two cytokines, IL-11 and IL-12 did not show significant
      differences between BP BF and sera, while an opposite behaviour was observed for
      transforming growth factor beta 1 (TGF-beta 1), whose serum levels were higher
      than the concentrations in BF. Using the number of lesions of the patients as a
      possible disease intensity marker, significant correlations were found with the
      BF levels of IL-1 beta, IL-8, TNF-alpha and, most closely, IL-5. These data may
      have pathogenetic relevance and suggest the possibility that these biological
      modulators may be used as a quantitative marker of disease intensity.

PMID- 9640365
TI  - Expression of CD26/dipeptidyl-peptidase IV in benign and malignant pigment-cell
      lesions of the skin.
AB  - The T-cell activation antigen CD26 or dipeptidyl-peptidase IV (DPP-IV) belongs to
      a group of membrane-bound proteases that are variably expressed by melanoma cell
      lines. In vitro studies have suggested that loss of CD26 is associated with
      tumour progression. To correlate its expression with the histological stage of
      tumour progression of malignant melanoma (MM), we studied the distribution of
      CD26/DPP-IV in paraffin sections of a series of 110 benign and malignant pigment
      cell lesions of the skin using a cocktail of anti-CD26 monoclonal antibodies and
      the three-step ABC method. Only two of 44 benign lesions focally expressed CD26
      in their junctional compartment. In MM, expression of CD26 was not related to any
      of the known histological prognostic factors, but was associated with the stage
      of tumour progression; thus, CD26 was expressed in the situ or invasive radial
      growth phase in 34% of MM, whereas only 12% of MM expressed CD26 in the vertical
      growth phase. No CD26 expression occurred in metastatic melanomas. These data
      suggest that this proteinase plays a part in the early invasion of MM. Thus, CD26
      may serve in the binding to, and enzymatic degradation, components of the
      extracellular matrix of the papillary dermis. Loss of CD26 in the vertical growth
      phase may contribute to the insufficient inactivation of regulatory peptides and
      unlimited action of growth factors.

PMID- 9640366
TI  - The intradermal effects of the H3 receptor agonist R alpha methylhistamine in
      human skin.
AB  - We have investigated the possible existence of the H3 histamine receptor in human
      skin with the highly selective ligands R alpha methylhistamine (RAMHA) (H3
      agonist) and thioperamide (H3 antagonist). We compared the intradermal effects of
      RAMHA with histamine, and studied their potential modulation by the H1 antagonist
      terfenadine, and H2 antagonist cimetidine. The effects of RAMHA and thioperamide
      on codeine phosphate-, substance P- and histamine-induced weal and flare
      responses were also studied. RAMHA produced dose-related weal and flare responses
      that were approximately 10- and fivefold less, respectively, than responses to
      histamine. Flare responses to RAMHA were significantly inhibited by oral
      terfenadine (P < 0.05). Weal and flare responses to histamine after oral
      cimetidine showed much intersubject variation, and cimetidine did not
      significantly alter either RAMHA- or histamine-induced weal and flare responses.
      Codeine phosphate-, substance P- and histamine-induced responses were not
      significantly affected by concurrent administration of RAMHA. Thioperamide was
      not found to influence codeine phosphate-, substance P-, RAMHA- or histamine
      induced effects. RAMHA induces vascular (weal and flare) responses in human skin,
      and these responses are partially inhibited by terfenadine. There is a trend for
      RAMHA to have an additive effect to the weal induced by substance P and
      histamine, although our results largely do not reach statistical significance.
      Thioperamide does not affect the vascular responses to RAMHA, codeine phosphate,
      histamine or substance P. We cannot conclude that the effects of RAMHA are
      induced by H3 receptors on cutaneous endothelial or mast cells.

PMID- 9640367
TI  - Celtic ancestry, HLA phenotype and increased risk of skin cancer.
AB  - Individuals of Celtic ancestry are claimed to be at greater risk of skin cancer
      than non-Celts, and various positive and negative associations between certain
      human leucocyte antigen (HLA) phenotypes and the development of skin cancer have
      been described. The aims of this study were to determine whether any HLA
      phenotypes are associated either with Celtic or non-Celtic ancestry, or skin
      type. One thousand and ten members of the Welsh Bone Marrow Donor Registry
      (WBMDR), whose HLA phenotypes are known, were asked to complete a questionnaire
      which enquired as to their family origins and their 'Index of Celtic Ancestry'
      scored out of 12. Three groups were identified: non-Celts (score < 3), Celts
      (score > 9), and a subset of the Celts--'high scoring' Celts (score > 10).
      Details of hair and eye colour and skin type were also requested. Skin type and
      HLA-A, -B, -DR and -DQ frequencies were compared between the three groups (Celts,
      non-Celts and 'high scoring' Celts), and a random indigenous population of 9196
      members of the WBMDR. Seven hundred and thirty-six replies were received (279
      male, 457 female, mean age 31 years). One hundred and forty-four Celts, 51 'high
      scoring' Celts and 170 non-Celts were identified. Forty-six (32%) Celts had skin
      type I or II compared with 36 (21%) non-Celts (P = 0.039), and 37 (73%) 'high
      scoring' Celts had skin type I or II (P < 0.0001). However, there were no
      significant differences between the groups with regard to hair colour, eye colour
      or number of episodes of painful sunburn. The frequency of HLA-DR4 was 32% in the
      non-Celtic group, 44% in the Celtic group (not significant), and 53% in the 'high
      scoring' Celts (P = 0.008). However, the difference was not significant after
      correction. There were no significant associations between skin type and HLA
      phenotype. HLA-DR4 is known to be associated with an increased risk of both basal
      cell carcinoma and malignant melanoma and its increased frequency in Celts may be
      an independent risk factor for skin cancer in addition to skin type.

PMID- 9640368
TI  - Effects of nitrazepam on nocturnal scratching in adults with atopic dermatitis: a
      double-blind placebo-controlled crossover study.
AB  - We investigated the effect of nitrazepam on nocturnal scratching in 10 adult out
      patients with atopic dermatitis (AD) using a double-blind placebo-controlled
      crossover method. Patients were given either nitrazepam (Benzalin tablets
      containing 5 mg nitrazepam) or a placebo on 3 successive nights, with a washout
      interval of 4 days. We used an infrared video camera to identify bouts of
      scratching lasting more than 5 s. These were counted and the duration of all the
      bouts of scratching (total scratching time, TST) was calculated. The percentage
      of TST to total recording time (TST%) was used as an index of nocturnal
      scratching. The frequency with which bouts of scratching (bouts/h) occurred was
      reduced by 10 mg nitrazepam (7.7 +/- 3.6 with nitrazepam vs. 9.6 +/- 3.6 with
      placebo, P < 0.05). However, the mean duration (s/bout) of the bouts of
      scratching was longer with 10 mg nitrazepam (32.3 +/- 23.4 with nitrazepam vs.
      19.1 +/- 10.0 with placebo, P < 0.05). As a result, there was no significant
      difference between TST% (6.5 +/- 4.2 with nitrazepam vs. 5.4 +/- 3.8 with
      placebo, not significant). All the above values are mean +/- SD. The degree of
      itching and the condition of the AD did not change during the 2 weeks of the
      study. We conclude that taking 10 mg nitrazepam is not an effective way of
      reducing the total duration of nocturnal scratching in AD patients, although it
      decreases the frequency with which bouts of nocturnal scratching occur.

PMID- 9640369
TI  - The characteristics of urticaria in 390 patients.
AB  - Data were collected on 390 patients who attended a dermatology out-patient
      department in whom a clinical diagnosis of urticaria was made. Two hundred and
      thirty-seven (61%) were women. The median age at onset of symptoms was 40 years.
      Sixty-one (16%) had acute urticaria with symptoms of less than 6 weeks duration
      at presentation. The disorder was deemed idiopathic in 217 (56%) patients, 59
      (15%) had physical urticaria and 57 (15%) had both idiopathic and physical
      urticaria. Thirty-eight (10%) patients reported intolerance to salicylate or
      similar drugs, and 31 of these 38 patients also had idiopathic symptoms. One
      hundred and seventy-two (44%) patients reported a good response to treatment with
      H1 receptor antagonists. Those who gained little or no benefit from these drugs
      were more likely to have a physical urticaria (P < 0.05) or to report intolerance
      reactions (P < 0.05). Only 113 (29%) patients were asymptomatic when discharged.
      One in five of a small sample contacted still had symptoms 10 years after
      presentation. Patients seen in an urticaria clinic were less likely to have
      routine investigations performed and more likely to be discharged at first
      attendance. When compared with previous published surveys, these figures show a
      lower proportion of intolerance reactions and a greater proportion of patients
      responding well to treatment with antihistamines.

PMID- 9640370
TI  - Successful treatment of facial blushing by endoscopic transthoracic
      sympathicotomy.
AB  - Facial blushing is one of the cardinal symptoms of social phobia and has a strong
      negative impact on the quality of life. Traditional therapeutic options are
      psychotherapy and pharmacological treatment. The results of these treatments on
      facial blushing are poorly documented. To investigate whether endoscopic
      bilateral transection of the upper thoracic sympathetic chain is efficient in the
      treatment of facial blushing, 244 consecutive patients were treated with
      bilateral endoscopic transthoracic sympathicotomy (ETS). The results were
      evaluated by questionnaire and symptoms assessed with visual analogue scales (0
      10). There was no mortality nor conversion to open surgery. No Horner's syndrome
      occurred. Two patients with postoperative pneumothorax were treated with
      intercostal drainage and one small pulmonary embolus was detected. The
      questionnaire was answered by 219 patients (90%) a mean (+/- SEM) of 8 months (+/
      9 days) after surgery. Facial blushing (mean +/- SEM) was reduced from 8.7 +/-
      0.1 to 2.2 +/- 0.2, P < 0.0001, by the operation. Heart palpitations in stressful
      situations were also reduced (3.7 +/- 0.3 to 1.3 +/- 0.1, P < 0.0001). The
      quality of life was substantially improved. The main side-effect was
      redistribution of sweating from the upper to the lower part of the body.
      Increased sweating of the trunk occurred in 75% of the patients. Overall, 85% of
      the patients were satisfied with the result and 15% were to some degree
      dissatisfied, mainly due to insufficient effect, but only four patients (2%)
      regretted the operation. As this is an open study, the results must be viewed
      with caution. ETS, however, appears to be an efficient, safe and minimally
      invasive surgical method for the treatment of facial blushing.

PMID- 9640371
TI  - Leucoderma treated by transplantation of a basal cell layer enriched suspension.
AB  - The aim of this study was to test the usefulness of a melanocyte-enriched cell
      suspension for the treatment of leucoderma. After removal of a superficial (4-30
      cm2) skin sample, the cells were mechanically separated in a trypsin-EDTA
      solution, centrifuged and washed in a melanocyte medium. The melanocyte-enriched
      epidermal cell suspension devoid of stratum corneum and stratum granulosum was
      then applied to the dermabraded depigmented skin. The 26 patients treated had
      piebaldism (three), vitiligo vulgaris (17), segmental vitiligo (three), halo
      naevi (one), naevus depigmentosus (one) and chemical leucoderma (one). In
      patients with widespread piebaldism we found that by diluting the cell suspension
      the recipient area could be increased to up to 10 times the size of the donor
      area with the same good results as without or with less dilution. In patients
      with vitiligo areas of between 50 and 90 cm2, the recipient areas were increased
      three- to fivefold in the donor area. Patients with piebaldism, segmental
      vitiligo and halo naevi healed completely, as did most patients with vitiligo. In
      naevus depigmentosus no effect was seen. Our new method for treatment of
      leucoderma has the advantage that cell culture is not needed and that it is more
      suitable than epidermal sheet grafts when several small areas are to be treated.

PMID- 9640372
TI  - The detection of human papillomavirus DNA in skin tags.
AB  - Human papillomavirus (HPV) is associated with benign cutaneous or mucosal lesions
      and with malignant tumours, but none of the HPV types has so far been related to
      skin tags. Skin biopsy specimens from 49 Caucasian patients suffering from the
      presence of multiple soft fibromas were analysed by means of dot blot
      hybridization and by polymerase chain reaction assays aimed at detecting all
      known HPV types. The results revealed the presence of HPV DNA type 6/11 in 88% of
      the skin tags examined. This result supports the hypothesis that HPV plays a part
      in the progression of cutaneous soft fibromas, as previously reported for
      laryngeal papillomas.

PMID- 9640373
TI  - Nodular localized cutaneous amyloidosis: further demonstration of monoclonality
      of infiltrating plasma cells in four additional Japanese patients.
AB  - Nodular localized cutaneous amyloidosis (NLCA) is a disorder characterized by
      deposition of amyloid derived from immunoglobulin light chains. We used semi
      nested polymerase chain reaction (PCR) to analyse archival paraffin-embedded
      sections from a previous patient and from four additional, previously reported
      patients with NLCA to determine whether involvement of monoclonal plasma cells is
      a universal feature of this condition. The semi-nested PCR analysis revealed one
      or two amplified bands, around 100-120 bp, for all five cases of NLCA, although
      the yields varied from case to case. These results suggest that clonal expansion
      of plasma cells in NLCA may occur locally.

PMID- 9640374
TI  - X-linked ichthyosis: relation between cholesterol sulphate,
      dehydroepiandrosterone sulphate and patient's age.
AB  - Steroid sulphatase deficiency is a feature of recessive X-linked ichthyosis
      (RXLI) that causes the accumulation of sulphated steroids (SS) in various organs
      and cells. In a previous study, we detected elevated cholesterol sulphate (CS)
      and dehydroepiandrosterone sulphate (DHEAS) serum levels in a group of 15 RXLI
      patients selected in a narrow age range. In the present study both CS and DHEAS
      serum levels were qualitatively and quantitatively determined using gas
      chromatographic analysis in a group of 33 RXLI patients ranging in age from 3 to
      70 years. The levels of CS and DHEAS were significantly increased in all
      patients. Variations in SS were related both to patients' ages and clinical
      course of the disease; Serum SS levels start to increase in early infancy, peak
      at puberty, remain elevated in adults and decrease slightly in the elderly.

PMID- 9640375
TI  - Prevalence of undetected tinea capitis in a prospective school survey in Madrid:
      emergence of new causative fungi.
AB  - From October 1994 to December 1996, a prospective study was undertaken in 10,000
      unselected school children in Madrid, aged between 2 and 16 years (mean +/- SD
      8.5 +/- 3.6 years). Fifty-two (0.52%) (including 13 immigrants from Africa) had
      dermatophytes in the scalp: 33 (0.33%) (including 10 immigrants from Africa) had
      tinea capitis and 19 were scalp carriers. Almost half of the symptomatic cases
      were caused by Trichophyton tonsurans (12 of 33 cases) and Microsporum canis (16
      of 33 cases). T. tonsurans (13 of 19 cases) was the predominant species in the
      scalp carriers. Twenty-four per cent of the subjects with tinea capitis and 42%
      of the asymptomatic scalp carriers also had ringworm in other body sites. There
      was a significantly higher occurrence of tinea capitis (P < 0.001) (particularly
      due to T. tonsurans: P < 0.001) and of asymptomatic scalp carriers (P < 0.05)
      (particularly due to anthropophilic species: P < 0.01) in the immigrant
      population from Africa.

PMID- 9640376
TI  - Prognostic implications of determining 180 kDa bullous pemphigoid antigen (BPAG2)
      gene/protein pathology in neonatal junctional epidermolysis bullosa.
AB  - Epidermolysis bullosa (EB) in neonates is often difficult to characterize, both
      in terms of making a precise diagnosis and in being able to comment accurately on
      the prognosis for the affected child. We present a case of a neonate with
      inherited mucocutaneous fragility and failure to thrive and detail our laboratory
      approach for classifying the subtype of EB in this child. Mutational analysis
      revealed a homozygous non-sense mutation in the gene encoding the 180 kDa bullous
      pemphigoid antigen, also known as type XVII collagen, predicting a non-lethal
      form of junctional EB. Identification of the underlying molecular pathology in
      this case was of use in improving diagnosis, classification, management and
      counselling.

PMID- 9640377
TI  - Localized mucosal involvement and severe pulmonary involvement in a young patient
      with paraneoplastic pemphigus associated with Castleman's tumour.
AB  - We describe a 19-year-old female patient who developed recurrent ulcerations
      limited to the orogenital mucosa for the last 3 years. She also developed
      dyspnoea 5 months after the onset of the orogenital lesions. Castleman's tumour
      of the retroperitoneum was found incidentally during routine physical
      examination. The diagnosis of paraneoplastic pemphigus (PNP) was made by
      pathological and immunological studies. The orogenital ulceration responded well
      to corticosteroid therapy, but severe bronchiolitis obliterans progressed despite
      intensive care. The patient eventually died from respiratory failure. This case
      demonstrates the diversity of clinical features of paraneoplastic pemphigus.

PMID- 9640378
TI  - Decreased activity of acid alpha-glucosidase in a patient with persistent
      periocular swelling after infusions of hydroxyethyl starch.
AB  - After infusion therapy with hydroxyethyl starch (HES) on account of sudden
      hearing loss, a 68-year-old woman developed a marked and persistent periocular
      swelling. This extraordinary adverse effect caused us to search for an
      explanation by means of histopathology, immunohistochemistry, immunoelectron
      microscopy and biochemistry. In lesional periocular skin and in normal-appearing
      skin, lysosomal storage of HES could be detected with a specific HES antibody in
      histiocytes, endothelial cells, basal keratinocytes and small nerves. In the
      periocular skin, a stronger deposition of HES was found in addition to distinct
      xanthomatous changes as well as features of lymphoedema. In view of lysosomal HES
      storage we measured the pH-dependent activity of the lysosomal alpha-glucosidase
      (GAA) in cultured fibroblasts. We found a 50% decreased activity of the acid GAA,
      which is consistent with a heterozygous state of glycogenosis type II (Pompe's
      disease) and potentially of pathogenetic relevance for the intralysosomal
      accumulation of HES. Xanthomatous changes and lymphoedema are likely to be
      secondary effects, but contribute considerably to the clinical manifestation of
      persistent visible swelling. This observation could point to a role for GAA in
      the elimination of tissue-stored HES. Patients with decreased activities of GAA
      may be at risk of unusual adverse effects following extraordinary and prolonged
      tissue storage of HES, especially if it is infused in large quantities.

PMID- 9640379
TI  - Clear cell papulosis of the skin.
AB  - Clear cell papulosis is a new entity first described in 1987. To date, six
      patients have been reported: all were young Taiwanese children. The disease is
      characterized clinically by multiple small, whitish maculopapules distributed
      along the milk line and by the presence of large, benign pagetoid cells in the
      epidermis resembling the clear cell of the nipple. The significance of this
      entity lies in its potential histogenetic link with Paget's disease of the skin.
      We report four new Taiwanese patients, three girls and one boy, aged between 21
      months and 4 years. Two were sisters. Small hypopigmented macules first appeared
      on the pubis. They were eventually distributed bilaterally along the milk line
      but were most numerous in the public area. The disease may easily be overlooked
      when the macules are tiny or few in number and thus display no clear milk-line
      distribution, or when they occur in white-skinned individuals. Histologically,
      solitary large clear cells with large, round pale nuclei were detected in the
      basal layer of the hypomelaninized epidermis. The numbers of clear cells varied
      on haematoxylin and eosin staining and were only small in two patients. The
      cytoplasm of the clear cells was decorated by antikeratin AE1 and
      anticarcinoembryonic antigen antibodies. AE1 was the best marker of the clear
      cell. Some of the AE1-positive cells were tadpole-like in shape and were situated
      well above the basal layer. Ultrastructurally, large clumps of disintegrated or
      vacuolated mucin granules were present in the cytoplasm of the clear cells. The
      melanocytes appeared normal; the suprabasal keratinocytes were essentially devoid
      of melanosomes. The pathological findings in the present study support the
      hypothesis that these clear cells are an aberrant derivative of sweat gland cells
      in the epidermis and are potentially the precursor cells giving rise to mammary
      and extramammary Paget's disease. The differential diagnosis includes chicken pox
      scars, idiopathic guttate hypomelanosis, hypomelanotic tinea versicolor,
      anetoderma and early, hypopigmented lesions of Paget's disease.

PMID- 9640380
TI  - Porokeratotic eccrine ostial and dermal duct naevus with dermatomal trunk
      involvement: literature review and report on the efficacy of laser treatment.
AB  - Porokeratotic eccrine ostial and dermal duct naevus (PEODDN) is a rare, benign
      hamartomatous malformation involving the eccrine sweat duct. The existence of
      filiform keratinous plugs that represent cornoid lamellae overlying dilated
      infundibula of eccrine ducts is a distinctive feature and the presence of
      associated abnormal dermal ducts is frequent. We report a patient with PEODDN who
      exhibited lesions on the left side of her chest. Cases of PEODDN reported in the
      literature are reviewed. Our experience in treating this patient with ultrapulsed
      carbon dioxide laser is also presented.

PMID- 9640381
TI  - Paget's disease of the scrotum: a case exhibiting positive prostate-specific
      antigen staining and associated prostatic adenocarcinoma.
AB  - A 75-year-old man with carcinoma of the prostate presented with a pruritic,
      erythematous plaque involving the scrotal skin. Histological examination revealed
      extramammary Paget's disease. The intraepidermal tumour cells expressed prostate
      specific antigen in keeping with a prostatic origin.

PMID- 9640382
TI  - Angiosarcoma arising in a chronically lymphoedematous leg.
AB  - Cutaneous angiosarcoma is a rare aggressive tumour of capillary and lymphatic
      endothelial cell origin. It presents as multiple purple and red papules and
      nodules on the head and neck or the extremities. We report an 86-year-old woman
      with angiosarcoma arising on her chronically lymphoedematous right leg. The
      lymphoedema, secondary to chronic immobility, had developed gradually over 40
      years. No other family members had lymphoedema. The patient presented with a
      plaque of friable tumour tissue on the lower right leg and dorsum of the foot,
      and satellite lesions on the knee and groin which initially appeared to be
      petechial haemorrhages. The satellite lesions in the groin grew into tumour
      nodules. There was no evidence of a preceding malignancy, nor any operative
      intervention to the affected limb or abdomen. Histological examination of all
      tumour specimens revealed moderately to poorly differentiated angiosarcoma. She
      died within 5 months of the first appearance of the skin nodules.

PMID- 9640383
TI  - Spindle and pseudoglandular squamous cell carcinoma arising in lichen sclerosus
      of the vulva.
AB  - An 83-year-old woman presented with a vulval mass. Radical vulvectomy was
      performed and histology showed a unique mixed picture of spindle, pseudoglandular
      and classical squamous cell carcinoma arising in vulval lichen sclerosus.

PMID- 9640384
TI  - Tripe palms associated with systemic mastocytosis: the role of transforming
      growth factor-alpha and efficacy of interferon-alfa.
AB  - Tripe palms are thickened, moss-like or velvety textured exaggerations of the
      normal dermatoglyphics. The disease belongs to the spectrum of papulosquamous
      paraneoplastic syndromes. Although suspected, the role of transforming growth
      factor-alpha (TGF-alpha) has not been clearly established. A 54-year-old man with
      systemic mastocytosis presented with thickening and darkening of the palms and
      soles. We performed skin biopsies for light microscopy (including toluidine
      blue), in situ hybridization and double labelling, and determination of serum
      tryptase, histamine and TGF-alpha levels. Toluidine blue stained the mast cells
      that had massively infiltrated the dermis. Tripe palm samples showed extensive
      hyperkeratosis. The TGF-alpha probe reacted strongly with the mast cells that
      also reacted with the antitryptase monoclonal antibody. Elevated tryptase,
      histamine and TGF-alpha levels prior to interferon-alfa administration decreased
      under treatment. The demonstration of TGF-alpha in infiltrating mast cells, the
      clinical regression of tripe palms and the lowering of the serum level and the
      mast cell molecular signal of the cytokine when systemic mastocytosis was
      controlled by interferon-alfa, suggest a key role for TGF-alpha in this cutaneous
      paraneoplastic syndrome.

PMID- 9640385
TI  - Nodular secondary syphilis.
AB  - Nodular secondary syphilis in a 23-year-old Indian man was characterized by
      numerous papular, nodular and plaque skin lesions, without involvement of the
      mucous membranes. The histopathology showed sarcoid-like granulomata with
      lymphocytes, histiocytes, eosinophils, plasma cells and multinucleated giant
      cells. The differential diagnosis included deep mycoses, leprosy, tuberculosis,
      sarcoidosis and lymphoma. The results of serological tests and the rapid response
      to penicillin indicated a correct diagnosis.

PMID- 9640386
TI  - DNA image cytometry in sebaceous tumours of the Muir-Torre syndrome.

PMID- 9640387
TI  - Terbinafine-induced lupus erythematosus.

PMID- 9640388
TI  - Terbinafine-induced acute generalized exanthematous pustulosis.

PMID- 9640389
TI  - Lamotrigine and phenobarbitone-associated hypersensitivity syndrome: resolution
      without corticosteroids.

PMID- 9640390
TI  - Flutamide-induced pseudoporphyria.

PMID- 9640391
TI  - Giant oral aphthous ulcers induced by nicorandil.

PMID- 9640392
TI  - Genital ulcers in a psoriasis patient using topical tazarotene.

PMID- 9640393
TI  - Hyperkeratotic varicella zoster virus infection in an HIV-infected patient.
      Successful treatment of persistent lesions with cryosurgery.

PMID- 9640394
TI  - Resolution of severe molluscum contagiosum on effective antiretroviral therapy.

PMID- 9640395
TI  - Nodular erythema elevatum diutinum in an HIV-1 infected woman: response to
      dapsone and antiretroviral therapy.

PMID- 9640396
TI  - Severe therapy-resistant necrotizing vasculitis associated with hepatitis C virus
      infection: successful treatment of the vasculitis with extracorporeal
      immunoadsorption.

PMID- 9640397
TI  - PUVA for diffuse cutaneous reticulohistiocytosis.

PMID- 9640398
TI  - Severe skin pain after combined ultraviolet B and ultraviolet A phototherapy for
      atopic dermatitis.

PMID- 9640399
TI  - Systemic plasmacytosis with deposition of interleukin (IL)-6 and elevated
      expression of IL-6 mRNA in the skin lesions.

PMID- 9640400
TI  - Irritant and allergic reactions are additive, not synergistic.

PMID- 9640401
TI  - Imaging of incidentally discovered adrenal masses.

PMID- 9640402
TI  - Selective oestrogen receptor modulators: potential therapeutic applications.

PMID- 9640403
TI  - The aetiology of Graves' disease: what is the genetic contribution?

PMID- 9640404
TI  - A population-based study of Graves' disease in Danish twins.
AB  - OBJECTIVE: The aetiology of Graves' disease (GD) is generally thought to fit a
      multi-factorial pattern of inheritance in which clinical disease develops on the
      basis of genetic susceptibility interacting with environmental and endogenous
      factors. In previous twin studies the probandwise concordance rates for
      hyperthyroidism were as high as 0.86 in monozygotic twins and 0.20 in dizygotic
      twins, indicating a very strong genetic influence. In these studies, however, no
      effort was made to distinguish between GD and non-autoimmune hyperthyroidism, and
      one study also included patients with simple non-toxic goitre, hampering if not
      invalidating any conclusions. The aim of the present study was to determine
      whether there is a genetic contribution in the aetiology of GD. DESIGN:
      Historical cohort study of pairs of same-sex twins, with information on GD being
      gathered by questionnaire surveys in the 1950s and 1960s. All available hospital
      material was sought to verify the diagnosis, which was assigned on the basis of
      clinical and histopathological evidence. The healthy co-twins were followed
      through middle age by questionnaire surveys in the 1970s and 1980s. PATIENTS:
      Same-sex twin individuals born between 1870-1920, included in a population-based
      nationwide register. A total of 118 subjects indicated hospitalization due to GD.
      A hospital record was available in 76 subjects. Of these, 55 (46 females and 9
      males) could be classified as having GD. MEASUREMENTS: Pairwise and probandwise
      concordance rates for GD in monozygotic and dizygotic twin pairs. RESULTS: The
      probandwise concordance rates were 0.36 for monozygotic pairs and 0 for dizygotic
      pairs. The pairwise concordance rates were 0.22 and 0 for monozygotic and
      dizygotic pairs, respectively. The concordance rates were significantly (P =
      0.012) higher in monozygotic than in dizygotic pairs. CONCLUSIONS: These results
      confirm that genetic factors play an important role in the aetiology of Graves'
      disease. However, they may not be as powerful as previously thought.

PMID- 9640405
TI  - Serum leptin and insulin in paediatric end-stage liver disease and following
      successful orthotopic liver transplantation.
AB  - OBJECTIVE: Leptin, the product of the ob gene, is a postulated feedback regulator
      of adiposity with appetite suppressant and catabolic effects. Catabolic states
      are associated with decreased body fat mass as a result of both nutritional and
      metabolic perturbation. Low serum leptin has been described previously in a
      number of catabolic states. It has been unclear whether the observed changes in
      leptin are a cause or consequence of changes in adiposity. Paediatric end-stage
      liver disease (ESLD) is characterized by decreased body fat mass and poor linear
      growth. Successful treatment by orthotopic liver transplantation (OLT) is
      accompanied by increase in fat mass. We investigated the hypothesis that serum
      leptin would be low in paediatric ESLD and that increase in body fat mass post
      OLT would result in increased serum leptin. DESIGN: Serum leptin and insulin were
      measured by radioimmunoassay in children with ESLD before and after successful
      OLT and in age-matched controls. PATIENTS: Twenty-four children with ESLD
      attending the outpatient department of King's College Hospital, London and 10 age
      matched controls. MEASUREMENTS: Anthropometric measurements were performed
      according to standard techniques and standard deviation (SDS) derived from
      population standards. Serum leptin and insulin were measured by radioimmunoassay.
      RESULTS: Serum leptin pre-OLT, leptin (4.06 micrograms/l, [3.45, 5.68] median,
      with 25th and 75th interquartile ranges) was significantly lower than controls
      (6.62 micrograms/l, [4.33, 8.05], P = 0.02). Following OLT, serum leptin fell to
      levels which were significantly lower than pre-OLT values (3.32 micrograms/l,
      [2.30, 3.99], P = 0.01). There was no significant difference between boys and
      girls either pre-OLT (boys; 3.64 micrograms/l, [2.45, 5.57], girls; 4.14
      micrograms/l, [3.18, 5.65]) or post-OLT (boys; 3.32 micrograms/l, [2.93, 3.62],
      girls; 3.69 micrograms/l, [2.23, 4.63]. Neither the age at OLT nor the age at the
      time of blood sampling was correlated with serum leptin pre-OLT or post-OLT. Pre
      OLT the children were significantly malnourished with low measures of body fat
      mass (mid-arm circumference (MAC) SDS -1.90 [-4.67, -1.07]; triceps skinfold
      thickness (TSF) SDS -1.53, [-2.23, -0.23]; body mass index (BMI) 16.2, [15.5,
      16.9]). Three months post-OLT, there were significant improvements in MAC SDS (
      0.77, [-1.08, -0.20], P = 0.02) and TSF SDS (-0.41, [-1.95, -0.38], P = 0.003),
      but no significant change in BMI (15.9 [15.3, 16.7], P = 0.41. Pre-OLT, log serum
      leptin did not correlate with BMI, MAC SDS or TSF SDS. In contrast, post-OLT,
      there was a positive correlation between log serum leptin and BMI (r = 0.59, P =
      0.003), MAC SDS (r = 0.49, P = 0.01) and TSF SDS (r = 0.41, P = 0.05). BMI also
      correlated with log serum leptin in the control children (r = 0.64, P = 0.04).
      CONCLUSIONS: Serum leptin is low in children with end-stage liver disease but
      does not show the expected correlation with measures of body fat mass.
      Surprisingly, following orthotopic liver transplantation serum leptin falls
      significantly despite significant increases in measures of body fat mass (triceps
      skinfold thickness standard deviation scores, mid-arm circumference standard
      deviation scores). Orthotopic liver transplantation restores the expected
      correlation of serum leptin with measures of body fat mass within the treatment
      group. The elevation of serum leptin above predicted levels in paediatric end
      stage liver disease offers a mechanism for the anorexia and cachexia
      characteristic of this disease.

PMID- 9640406
TI  - Effect of isoprenaline on plasma leptin and lipolysis in humans.
AB  - OBJECTIVE: The sympathetic nervous system may play a central role in the
      regulation of both lipolysis and leptin production. Therefore, we investigated
      the effect of intravenous infusions of the beta-adrenergic agonist isoprenaline
      on plasma concentrations of leptin and nonesterified fatty acids. DESIGN AND
      PATIENTS: Eight lean, healthy human volunteers, (4M:4F; median (interquartile
      range) age 36.5 (30.8-40.0) years; BMI 22.9 (20.1-29.2) kg.m-2; % body fat 24.5
      (17.9-26.3)), were studied following an overnight fast. Intravenous infusion of
      isoprenaline was carried out for 3 h, followed by a 1 hour recovery phase. The
      isoprenaline infusion rates (0.5-3.5 micrograms.min-1) were titrated individually
      for each subject in order to achieve similar biological sympathetic responses
      based on heart rate (target heart rates were > 100 min-1 but < twice resting
      heart rate). MEASUREMENTS: Plasma leptin was determined using an in-house
      radioimmunoassay, nonesterified fatty acids estimated with an enzymatic
      colourimetric assay and insulin concentrations were assayed using a specific, two
      site immunoenzymometric assay. RESULTS: Fasting preinfusion plasma leptin
      concentrations (6.3 (3.0-12.8) micrograms/l) correlated with percentage body fat
      measured by bioimpedance (r = 0.95; P < 0.001). Plasma leptin concentrations were
      rapidly suppressed by isoprenaline, with maximal suppression (20.5 (15.0-25.0)%
      of preinfusion levels (Wilcoxon rank sum test; P < 0.05)), observed after 2 h. In
      the recovery period, plasma leptin concentrations rapidly returned to preinfusion
      levels (postinfusion vs maximally suppressed leptin concentrations P < 0.05; vs
      preinfusion leptin concentrations P = NS). Plasma nonesterified fatty acids and
      insulin concentrations showed opposite changes to those observed with leptin.
      CONCLUSION: Plasma leptin concentrations are rapidly and reversibly suppressed by
      the infusion of isoprenaline in humans in vivo.

PMID- 9640407
TI  - Serum follistatin concentrations are increased in patients with septicaemia.
AB  - OBJECTIVE: Follistatin (FS) is the specific binding protein of activin, a growth
      and differentiation factor of many cell types. Both factors have almost
      ubiquitous tissue distributions. In vitro, FS is secreted by vascular endothelial
      cells and this can be stimulated by bacterial compounds. For this reason, serum
      FS levels were examined in patients with septicaemia. PATIENTS: Five male and
      four female patients of different age with various forms of septicaemia and
      different clinical outcome. MEASUREMENTS: Serum concentrations of FS, C-reactive
      protein (CRP) and blood leucocyte counts were determined repeatedly in all nine
      patients; samples from age- and sex-matched healthy volunteers served as
      controls. RESULTS: The median of the maximum FS concentrations of septicaemic
      patients was threefold higher than in healthy controls (P = 0.008). The highest
      increase observed was approximately 40 times normal. Serum FS levels in patients
      with septicaemia showed large variations between individuals. Serum FS levels
      parallelled those of CRP but were not correlated to the leucocyte counts.
      CONCLUSION: Serum follistatin concentrations in humans are elevated during
      septicaemia and appear to parallel serum C-reactive protein levels.

PMID- 9640408
TI  - An audit of the management of thyroid cancer in a district general hospital.
AB  - OBJECTIVE: Thyroid cancer is the commonest endocrine malignancy yet it appeared
      to present infrequently to the endocrinologists at this large District General
      Hospital. The management of well-differentiated thyroid cancer remains
      controversial with a wide variation in clinical practice. The aim of this survey
      was to determine the characteristics of the patients diagnosed with thyroid
      cancer and whether any deficiencies existed in the management of subjects
      diagnosed with thyroid cancer over a five-year period using standards of care
      based upon long-term outcome data and recently published USA guidelines. DESIGN
      AND PATIENTS: Retrospective case-note survey of all patients newly registered
      with thyroid cancer from 1990 to 1994 in North Staffordshire (estimated total
      population 450,000). RESULTS: The annual incidence of all thyroid cancer was two
      per 100,000 of which well-differentiated tumours comprised 70%. Medical records
      were obtained in 48 new cases (91% of total) identified. Fifteen subjects who
      presented as surgical emergencies received only palliative treatment and had a
      poor outcome. Two patients presented with metastatic medullary thyroid carcinoma
      (3% of total). Thirty-one patients (97% of whom presented with a thyroid nodule)
      were referred electively to either surgical (n = 22), ENT (n = 2) or
      endocrinology (n = 7) outpatients with well-differentiated papillary (n = 17) and
      follicular (n = 14) tumours. Thirteen patients (42%) had fine-needle aspiration
      cytology performed preoperatively. Of the 22 tumours (71%) greater than 1.5 cm,
      five (27%) had a total thyroidectomy and two (9%) also had radioiodine ablation.
      There was inadequate serum thyrotrophin suppression postoperatively in 12
      patients (39%) and only five (16%) were being monitored for recurrence with serum
      thyroglobulin measurements. CONCLUSIONS: Deficiencies in the optimum management
      of small, well-differentiated thyroid cancers were identified. Improved
      communication between specialties has led to the development of an agreed
      management protocol to increase the quality of care offered to patients with
      thyroid cancer and for auditing the coordinated service in the future.

PMID- 9640409
TI  - Retinoid X receptor expression in the normal pituitary and clinically 'non
      functioning' pituitary tumours.
AB  - OBJECTIVE: The glycoprotein hormone common alpha-subunit is frequently expressed
      in clinically 'non-functioning' tumours (NFTs) of the anterior pituitary, despite
      normal levels of T3 and gonadal steroids. This observation suggests abnormal
      negative-feedback regulation of the alpha-subunit by T3 and gonadal steroids in
      NFTs. We have previously documented reduced expression of thyroid hormone
      receptor (TR) variants in NFTs compared to normals and proposed that this
      observation may, in part, explain the defective negative regulation. Due to the
      important role of retinoid X receptors (RXRs) in transactivating TR-mediated
      transcriptional regulation, via heterodimer formation, we hypothesize that
      aberrant RXR isoform expression in NFTs may contribute to the defective negative
      regulation of the alpha-subunit by T3. DESIGN: Comparison of RXR isoform protein
      and mRNA expression in NFTs and normal pituitaries. PATIENTS AND TUMOURS: Twenty
      clinically non-functioning pituitary tumours and 27 normal pituitaries were
      obtained for analysis. MEASUREMENTS: Immunocytochemistry and semiquantitative RT
      PCR was performed on tumours and normal pituitaries to determine the relative
      levels of expression of RXR isoform proteins and mRNAs, respectively. RESULTS:
      RXR alpha was expressed in a similar proportion (approximately 50%) of both
      normal human pituitaries and NFTs, while RXR beta and gamma were each observed in
      26% of normals but were undetectable in NFTs. The application of semiquantitative
      RT-PCR revealed similar levels of mRNAs encoding the RXR alpha and RXR beta
      isoforms in normals and NFTs but significantly reduced expression of RXR gamma
      mRNA was observed in NFTs. CONCLUSIONS: We propose that abnormal RXR isoform
      expression in clinically 'non-functioning' pituitary tumours may contribute to
      abnormal T3-mediated negative regulation of alpha-subunit production.

PMID- 9640410
TI  - Clinical profile of primary hyperparathyroidism in adolescents and young adults.
AB  - OBJECTIVE: Primary hyperparathyroidism (PHPT) is an uncommonly diagnosed
      condition among adolescents and young adults. We review the clinical
      characteristics of these patients based on our institutional experience.
      SUBJECTS: Patients aged 12-28 years treated for PHPT at our institution from 1990
      to 1996 were evaluated by a review of medical records and current follow-up data.
      This consisted of 22 patients (8M:14F), constituting approximately 3% of all
      patients operated for PHPT during this period. MEASUREMENTS: Serum and urinary
      calcium concentrations, renal function, and serum intact parathyroid hormone
      (IPTH) levels were measured in all patients. After biochemical confirmation of
      diagnosis, the patients completed a questionnaire to evaluate the presence of
      symptoms and/or conditions associated with PHPT. All the patients underwent
      parathyroidectomy and their tumour characteristics were evaluated. Surgical
      outcome was determined by measurements of serum calcium and IPTH levels
      postoperatively and during long-term follow-up. RESULTS: A third of the patients
      were diagnosed by routine serum chemistry whereas two-thirds presented with
      symptoms or conditions associated with hypercalcaemia. Non-specific complaints
      such as fatigue or exhaustion, and weakness or lethargy constitute the most
      common findings on questionnaire review. A family history of PHPT was present in
      only 2 patients. The preoperative peak serum calcium levels ranged from 2.67 to
      4.19 mmol/l (norm: 2.10-2.54 mmol/l), with a median of 3.07 mmol/l. Surgical
      pathologies revealed 59% solitary adenoma, 27% hyperplasia, 9% multiple adenomas
      and 5% carcinoma. Comparison between the adolescents (aged 12-18 years) and young
      adults (aged 19-28 years) revealed no differences in the clinical, pathological
      or laboratory profiles, except for a male predominance in adolescent patients.
      Fifteen patients had resection of one or more adenomas while 7 underwent subtotal
      parathyroidectomy. Six patients (27%) were reoperated cases, all received primary
      treatment elsewhere. All patients with benign PHPT were cured surgically, with a
      median follow-up of 47 months (range 3-77 months). One reoperated patient
      developed permanent hypocalcaemia. One patient with carcinoma underwent several
      operations for recurrence; he is now eucalcaemic despite persistent disease at 80
      months from diagnosis. CONCLUSIONS: We found a high incidence of multiglandular
      disease and relatively non-specific symptomatology in our adolescent and young
      adult patients with primary hyperparathyroidism. In view of the heterogeneous
      clinical expression noted in young patients, one should consider primary
      hyperparathyroidism in the differential diagnosis of unexplained non-specific
      complaints, and perform serum calcium estimations more readily in these subjects.
      Our experience suggests that primary hyperparathyroidism can be a serious disease
      with significant morbidity if left untreated, whereas parathyroidectomy provides
      successful results.

PMID- 9640411
TI  - TSH receptor antibody-associated thyroid dysfunction following subacute
      thyroiditis.
AB  - OBJECTIVE: Autoimmunity plays an important role in the development of
      thyrotrophin (TSH) receptor antibodies and the pathogenesis of Graves' disease
      and Hashimoto's thyroiditis. On the other hand, subacute thyroiditis is a self
      limited inflammatory disease of presumed viral aetiology. The aim of this study
      was to examine whether subacute thyroiditis triggers TSH receptor antibody
      associated thyroid disorders. PATIENTS: We reviewed 1,697 patients with subacute
      thyroiditis seen between 1985 and 1995. DESIGN AND MEASUREMENTS: We measured
      antibodies which inhibit the TSH binding to the TSH receptor (TBIAb), thyroid
      stimulating antibodies (TSAb) and antibodies that block TSH action (TBAb). Other
      thyroid autoantibodies were also determined. RESULTS: TBIAb became positive in 38
      patients following subacute thyroiditis. Thyroid function after the development
      of TBIAb appeared to be influenced by the bioactivity of the antibody.
      Hyperthyroidism developed in the presence of TSAb, and so did hypothyroidism in
      the presence of TBAb, although 21 patients did not have thyroid dysfunction
      despite high titres of TBIAb. Fifteen out of 17 patients recovered from
      hyperthyroidism or hypothyroidism after the disappearance of TBIAb sometimes even
      without medication. TBIAb-positive patients had a high incidence of a family
      history of thyroid disease and positive anti-thyroid microsomal antibodies. An
      ophthalmopathy similar to Graves' disease was also observed in 3 patients.
      CONCLUSIONS: Subacute thyroiditis may trigger autoreactive B cells to produce TSH
      receptor antibodies, resulting in TSH receptor antibody-associated thyroid
      dysfunction in some patients.

PMID- 9640412
TI  - Serum collagen crosslinks as markers of bone turn-over during GH replacement
      therapy in growth hormone deficient adults.
AB  - OBJECTIVES: Bone metabolism is an important target for GH replacement therapy.
      However, in adults, treatment periods exceeding 12 months are required for a
      positive effect of GH on bone mineral density. Thus, to detect an early effect of
      GH on bone, markers of bone turn-over are important. Pyridinoline (PYR) and
      deoxypyridinoline (DPYR) are well-defined sensitive markers of bone resorption,
      but to date only urinary assays have been available. We report the use of a novel
      assay to measure changes in serum PYR and DPYR in GH deficient (GHD) adults
      during GH replacement therapy. STUDY DESIGN: The study consisted of a 6-month
      randomized, double-blind, placebo-controlled study of the administration of GH
      (Genotropin) (0.25 IU/Kg/week (0.125 IU/kg/week for the first four weeks))
      followed by a 6-month open phase of GH therapy. PATIENTS: Thirty-five GHD adults
      (17 women; mean age 39.8 years; range 21.1-59.9) on conventional hormone
      replacement therapy as required, were studied. MEASUREMENTS: Bone formation was
      analysed using serum bone alkaline phosphatase (BAP) and serum osteocalcin (OC).
      Bone resorption was analysed using serum pyridinoline (PYR) and serum
      deoxypyridinoline (DPYR). Bone mineral density (BMD) was determined by dual
      energy X-ray absorptiometry (DEXA). RESULTS: After 6 months placebo treatment
      there were no significant changes in any of the bone markers analysed, nor in
      BMD. In the active arm of the study there was a significant increase in serum OC,
      BAP, PYR and DPYR (P = 0.03, P = 0.004, P = 0.003 and P = 0.01, respectively),
      remaining significantly elevated over their baseline levels for the subsequent 6
      months of treatment (P = 0.04, P = 0.009, P = 0.003 and P = 0.04, respectively).
      No changes were observed in BMD in any of the groups after 6 months GH treatment.
      In the active arm of the study, after 12 months GH treatment there was a
      significant increase in BMD at both the lumbar spine and femoral neck (P = 0.01
      for both sites). CONCLUSIONS: In summary, the present study confirms that
      administration of GH treatment to GHD adult patients significantly activates bone
      remodelling, with the effect of GH both in bone formation and bone resorption
      markers being maximal after 6 months of treatment. The serum assay for PYR and
      DPYR has a number of practical and theoretical advantages over the urine assay
      and gave similar results to those previously reported for the urine assay.

PMID- 9640413
TI  - Long-term change in the bone mineral density of adults with adult onset growth
      hormone (GH) deficiency in response to short or long-term GH replacement therapy.
AB  - OBJECTIVE: Only two previous studies have assessed the effects of long-term GH
      replacement therapy on bone mineral density (BMD) in patients with adult onset GH
      deficiency. To date no study has looked at the long-term impact on BMD after a
      short course (6-12 months) of GH replacement. In two groups of patients with
      adult onset GH deficiency we have studied BMD either (a) after 3 years of
      continuous GH replacement or (b) 2 years after completion of a short course of
      GH. DESIGN: An open GH therapeutic study in which patients were recruited from a
      previous double-blind placebo-controlled study. The BMD status of all patients
      was unknown to the physician and patient at the time of recruitment. PATIENTS:
      Group A (n = 7, three females) all received GH replacement continuously for 3
      years. Group B (n = 8, five females) included six patients who received GH
      replacement for 6 months and two who received GH replacement for 12 months with
      BMD being measured at 6-monthly intervals. METHODS: Single photon absorptiometry
      (SPA) and later single X-ray absorptiometry (SXA) were used to measure forearm
      cortical BMD. Dual-energy X-ray absorptiometry (DXA) was used to measure lumbar
      spine, trochanteric, femoral neck and Ward's area BMD. RESULTS: In group A lumbar
      spine and trochanter BMD had increased significantly from baseline by 3.7% (DXA:
      median change = 0.045 g/cm2; P = 0.028) and 4.0% (DXA: median change = 0.031
      g/cm2; P = 0.046), respectively. There were non-significant decreases in femoral
      neck (1.9%) (DXA: median change = -0.02 g/cm2; P = 0.39), Ward's area (6.5%)
      (DXA: median change = -0.06 g/cm2; P = 0.09) and forearm (2.6%) (SPA/SXA: median
      change = -0.013 g/cm2; P = 0.18). In group B, compared with baseline, only
      trochanter BMD changed significantly, increasing by 5.9% (DXA: median change =
      0.0485 g/cm2; P = 0.049). Lumbar spine (DXA: median change = -0.001 g/cm2) Ward's
      area (DXA: median change = 0.0135 g/cm2), femoral neck (DXA: median change = 
      0.005 g/cm2) and forearm cortical (SPA/SXA; median change = -0.01 g/cm2) BMD did
      not change significantly (P = 0.67, P = 0.57, P = 0.86 and P = 0.31,
      respectively). Median percentage changes compared with baseline were -0.1%, 1.8%,
      -0.5% and -2.1%, respectively. From the time of completion of GH therapy however,
      BMD increased significantly at lumbar spine, (median change = 0.023 g/cm2),
      Ward's area (median change = 0.03 g/cm2) and trochanter (median change = 0.056
      g/cm2) (P = 0.036, P = 0.049 and P = 0.012, respectively) but not at the femoral
      neck (median change = 0.017 g/cm2; P = 0.31) or forearm (median change = 0 g/cm2;
      P = 0.75). CONCLUSION: Long-term GH replacement therapy for three years appears
      to have beneficial effects on bone in patients with adult onset GH deficiency
      particularly at the lumbar spine and trochanter; the effects on femoral neck and
      forearm cortical BMD, however, are less impressive. A short course (6-12 months)
      of GH replacement therapy results in an increase in trochanter BMD several years
      later, and after an initial decline in BMD whilst on GH replacement, lumbar spine
      and Ward's area BMD return towards their baseline values. These results emphasize
      that not all types of bone and skeletal sites respond to GH therapy identically.
      Furthermore a short course of GH replacement over 6-12 months may result in
      significant changes in BMD several years later.

PMID- 9640414
TI  - Serum free IGF-I, total IGF-I, IGFBP-1 and IGFBP-3 levels in an elderly
      population: relation to age and sex steroid levels.
AB  - BACKGROUND: Most previous studies concerning the relationship between IGF-I and
      age used assays measuring total IGF-I. Although free IGF-I is considered of
      greater biological relevance, little is known about its relationship with sex
      steroids levels in elderly healthy subjects. MEASUREMENTS: In a cross-sectional
      study of 218 healthy people (103 men, 115 women) aged 55-80 years we measured
      serum total and free IGF-I, IGFBP-1 and IGFBP3 levels and sex steroids. Free
      androgen index and free oestradiol index were used as an indicator for free
      oestradiol and free testosterone levels, respectively. RESULTS: Free IGF-I levels
      did not decline with age in the whole study population. Free IGF-I levels even
      increased in individuals above 70 years of age in comparison to those aged
      between 55 and 70 years (mean +/- SE 0.106 +/- 0.007 nmol/l vs. 0.086 +/- 0.004
      nmol/l, P = 0.009). Total IGF-I and IGFBP-3 decreased with age (r = -0.20, P =
      0.005 and r = -0.24, P = 0.001, respectively). Total IGF-I levels were positively
      related with free oestrogen index in both sexes. Free IGF-I did not relate to
      free oestrogen or androgen index. In women only, free IGF-I was related
      positively with DHEAS while IGFBP-1 was inversely correlated with DHEAS.
      CONCLUSIONS: Free IGF-I levels do not decrease with age and are even higher in
      individuals above 70 years. There was no relationship between free IGF-I and free
      androgen or oestrogen index in either gender. We hypothesize that higher free IGF
      I levels in older persons may be the consequence of selective survival in the
      cohort: subjects with high free IGF-I levels may live longer. The absence of a
      relationship between free IGF-I levels and free androgen and oestrogen indices
      suggests that there is no direct interaction between the biological activity of
      circulating IGF-I levels and sex hormone production in a healthy ageing
      population.

PMID- 9640415
TI  - Determinants of serum insulin-like growth factor I in growth hormone deficient
      adults as compared to healthy subjects.
AB  - OBJECTIVE: Growth hormone status is an important determinant of serum IGF-I but
      it is well known that hypopituitary adults with pronounced GH-deficiency (GHDA)
      may exhibit normal IGF-I levels. To elucidate possible causes of this apparent
      paradox we compared the significance of putative IGF-I predictors in GHDA and
      normal subjects. DESIGN: A cross-sectional study. SUBJECTS: Twenty-seven GHDA (9
      females, 18 males, mean +/- SE age 44 +/- 1 years) and 27 healthy control
      subjects (9 females, 18 males, mean +/- SE age 43 +/- 2 years). RESULTS: Serum
      IGF-I and IGFBP-3 were significantly lower in GHDAs, but a considerable overlap
      existed (IGF-I (microgram/l) 87 +/- 12 (GHDA) vs 177 +/- 10 (Control) (P <
      0.001)). In both Controls and GHDA, IGF-I was higher in males than females
      (Control: 196 +/- 12 vs 138 +/- (P = 0.004); GHDA: 97 +/- 16 vs 56 +/- 11 (P =
      0.05)). In GHDA, males on testosterone substitution had the highest IGF-I
      concentrations. The molar IGF-I:IGFBP-3 ratio was significantly lower in GHDAs
      (0.18 +/- 0.01 vs 0.23 +/- 0.02 (P = 0.002)). IGFBP-1 (microgram/l) was
      significantly elevated in GHDAs (6.28 +/- 1.11 vs 3.07 +/- 0.32 (P < 0.001))
      despite comparable fasting insulin levels. Percentage total body fat (TBF, DEXA,
      waist/hip ratio, and intra-abdominal fat (CT) were all elevated in GHDAs. IGF-I
      correlated positively with lean body mass (DEXA) and negatively with TBF and
      IGFBP-1 in both groups. IGF-I correlated negatively with age in CON but not in
      GHDAs, whereas IGF-I correlated positively with IGFBP-3 only in GHDAs. Multiple
      regression analysis revealed that age and IGFBP-1 were the only significant
      predictors of IGF-I in CON, whereas IGFBP-3 and, to a lesser extent TBF, were the
      only independent predictors of IGF-I in GHDAs. Neither peak stimulated GH, nor
      physical fitness contributed in any equations in the two groups. CONCLUSIONS: 1)
      IGF-I levels are regulated by several variables in addition to GH status 2) age
      per se is an independent negative determinant in healthy subjects but not in GHDA
      3) it is probable that some cases of paradoxically high IGF-I levels in GHDA are
      secondary to inappropriately elevated IGFBP-3 levels. 4) in mid-adulthood males
      have higher IGF-I levels than females and it is likely that testosterone directly
      stimulates IGF-I. The influence of gender and sex steroids must therefore be
      accounted for when comparing IGF-I levels between hypopituitary and healthy
      subjects.

PMID- 9640416
TI  - Serum concentrations of insulin, insulin-like growth factor(IGF)-I, IGF binding
      protein (IGFBP)-1 and -3 and growth hormone binding protein in obese children:
      fasting IGFBP-1 is suppressed in normoinsulinaemic obese children.
AB  - OBJECTIVE: Simple obesity is characterized by normal or accelerated growth in the
      presence of reduced serum levels of GH, whereas its detailed mechanism remains
      unknown. We, therefore, evaluated interrelationships among serum levels of
      insulin, IFG-I, IGF binding protein (IGFBP)-1 and -3 and growth hormone binding
      protein (GHBP) in prepubertal obese children. SUBJECTS: Prepubertal 20 obese
      children and 20 age-matched control children were included in the study. RESULTS:
      Serum levels of insulin, IGF-I and IGFBP-3 in obese children did not differ from
      those in controls. The serum level of IGFBP-1 was significantly lower in obese
      children (22.1 +/- 18.4 micrograms/l, P < 0.001) than in control children (76.0
      +/- 62.9 micrograms/l). No relationship was found between the serum levels of
      insulin and IGF-I, IGFBP-1, or IGFBP-3 in obese subjects. The serum level of GHBP
      in obese children was significantly elevated as compared with that in controls
      and was positively correlated with body mass index (BMI). No relationship was
      found between the serum levels of GHBP and IGF-I in obese subjects. CONCLUSIONS:
      The present study showed for the first time that the fasting IGFBP-1 level was
      suppressed in prepubertal obese children with fasting normoinsulinaemia. We
      speculate that the hyperinsulinaemia which cannot be detected in the fasting
      state may have suppressed hepatic production of IGFBP-1. Alternatively, the
      reduced IGFBP-1 is likely to be a compensatory response to impaired insulin
      sensitivity. Thus, the IGFBP-1 level may be a useful predictor for the early
      identification in the development of insulin resistance in prepubertal obese
      children.

PMID- 9640417
TI  - Corticotroph axis sensitivity after exercise in endurance-trained athletes.
AB  - OBJECTIVE: The present study was conducted in order to describe human hypothalamo
      pituitary adrenal (HPA) axis adaptation in a model of repeated physical stress
      (endurance training) that causes a moderate increase in cortisol levels.
      SUBJECTS: We performed the same stimulation tests (adrenal stimulation with ACTH
      or pituitary stimulation with combined CRH/LVP) in a population of 8 endurance
      trained athletes in two distinct situations: resting (baseline cortisol values)
      and 2 h after the end of strenuous exercise (increased cortisol values) to
      evaluate the HPA axis sensitivity to endogenous sustained increases in cortisol
      concentrations. MEASUREMENTS: During these tests, saliva and plasma cortisol (Fs
      and Fp, respectively) were assessed and compared. RESULT: Cortisol values in both
      plasma and saliva at the end of 2 h of exercise were significantly higher than in
      rested controls: Fs 11.5 +/- 1.3 vs 6.5 +/- 0.8 nmol.l-1 and Fp 428 +/- 36 vs 279
      +/- 27 nmol.l-1 (post exercise vs post rest sessions, respectively, P < 0.001 for
      both). After either hormone test (CRH/LVP or ACTH), cortisol levels in plasma and
      saliva increased similarly when rest was compared to post exercise. Saliva
      variations (delta %) under exogenous hormone stimulation were dramatically
      greater than plasma variations. For example, under ACTH stimulation, the relative
      increments in cortisol were on control day: delta Fs 980 +/- 139 vs delta Fp 218
      +/- 43% (saliva vs plasma, respectively, P < 0.05) and on exercise day: delta Fs
      605 +/- 89 vs delta Fp 102 +/- 14% (saliva vs plasma, respectively, P < 0.05).
      CONCLUSIONS: In endurance-trained athletes, displaying a moderate but sustained
      endogenous cortisol increase: (1) ACTH responses following pituitary stimulation
      are not blunted, (2) cortisol responses following maximal adrenal stimulation are
      not blunted. Our results favour the hypothesis of a decreased pituitary
      sensitivity to cortisol negative feedback whereas the hypothesis of a major
      decreased adrenal sensitivity to ACTH was discarded. The greater ability of
      saliva assays to detect a cortisol increase strongly supports its use in the
      study of HPA physiology, whether under basal or dynamic conditions.

PMID- 9640418
TI  - Overnight urinary free cortisol determination: a screening test for the diagnosis
      of Cushing's syndrome.
AB  - OBJECTIVE: The collection of urine over 24 h to measure free cortisol (UFC) is
      used to diagnose Cushing's syndrome. However, a complete collection of urine is
      not easy to achieve and the sampling is frequently inaccurate, so a 24 h
      collection for the determination of UFC excretion is used as a confirmatory
      rather than a screening test for Cushing's syndrome. Our objective was to
      evaluate a more convenient urine collection for screening patients suspected of
      Cushing's syndrome. DESIGN: We have studied the possibility of using night-time
      (from 2000 h to 0800 h) UFC excretion as a screening test for Cushing's syndrome
      ('overnight UFC'). PATIENTS: Thirty patients with proven Cushing's syndrome were
      studied before treatment (21 cases of Cushing's disease, two cases of ectopic
      ACTH secretion, seven of adrenal adenoma). The results were compared to those
      from 150 control obese subjects. MEASUREMENTS: Overnight UFC, and creatininuria
      (UC), were evaluated at least once in the patients and in all subjects. The 24 h
      UFC and UC were determined at least once in the patients and in 56 control
      subjects. RESULTS: The overnight UFC/UC ratio clearly separated all but one
      patient of the two groups: 194 +/- 386 vs 5.7 +/- 3.4 nmol/mumol (P < 0.0005)
      (ranges 16.2-2024 vs 0.6-17.4, Cushing's syndrome vs controls, respectively). The
      only patient with Cushing's syndrome who had an overnight UFC/UC ratio that
      overlapped with that of controls suffered from renal failure. The 24 h UFC/UC
      ratio of the patients differed from the ratio of controls: 184 +/- 365 vs 8.4 +/-
      4.1 nmol/mumol (P < 0.0005) (ranges 14-1639 vs 1.5-21.2, respectively). Four
      patients with Cushing's syndrome had 24 h UFC/UC ratios lower than the upper
      control ratio. CONCLUSION: The overnight urinary sampling is a simple procedure
      compared to the 24 h urine collection performed in out-patients. For a
      sensitivity set at 100%, the specificities were 97% for the overnight UFC/UC
      ratio and 87% for the 24 h-UFC/UC ratio. This therefore appears to provide a good
      screening method for Cushing's syndrome.

PMID- 9640419
TI  - Corticosteroid metabolism in human granulosa-lutein cells.
AB  - OBJECTIVE: The aims of this study were to determine the type and level of 11 beta
      hydroxysteroid dehydrogenase (11 beta HSD) in human granulosa-leutein cells (GLE)
      shortly before ovulation and to correlate activity with the outcome of treatment
      in patients undergoing in vitro fertilization and embryo transfer (IVF/ET).
      DESIGN: GLC from 32 patients undergoing IVF/ET were tested for type and level of
      11 beta HSD activity in relation to treatment outcome. PATIENTS: Periovulatory
      follicles were aspirated by ultrasound guided transvaginal puncture following a
      standard controlled ovarian stimulation protocol, approximately 36 h after
      administering an ovulation-inducing dose of human chorionic gonadotrophin (HCG).
      GLC were separated from follicular fluid by density-gradient centrifugation and
      taken for measurement of 11 beta HSD activity in vitro; oocytes were used for
      IVF/ET. MEASUREMENTS: Interconversion of cortisol (F) and cortisone (E), and
      dexamethasone (D) and 11-dehydrodexamethasone (DHD) was measured in standardized
      assays comprising incubation of GLC with 3H-labelled substrate, with separation
      of substrate and product by thin-layer radiochromatography. RESULTS: Conversion
      of F to E varied from 10.5 to 30.9% while that of E to F was between 2.4 and
      44.6%. In the GLC of 25 patients in whom both activities were measured,
      dehydrogenase (F to E) activity predominated in 13 and reductase (E to F) in 12.
      By contrast, D (substrate for 11 beta HSD2 but not 11 beta HSD1) showed less than
      1% metabolism in this system while DHD (substrate for 11 beta HSD1 and 11 beta
      HSD2) was converted significantly (65.6-90.5%) to D in the four patients tested.
      There was no significant difference in the interconversion of F and E between
      patients who became pregnant and those who did not. CONCLUSIONS: The
      dehydrogenase and oxoreductase reactions catalysed by 11 beta HSD both occur in
      granulosa-lutein cells at the time of follicular rupture, probably due to 11 beta
      HSD1. A lack of measurable conversion of dexamethasone to 11-dehydrodexamethasone
      suggests that dehydrogenation due to 11 beta HSD2 is low or absent. Neither type
      nor level of 11 beta HSD activity measured under the present assay conditions
      correlates with IVF outcome.

PMID- 9640420
TI  - Lipoprotein lipase mass and activity in post-heparin plasma from subjects with
      intra-abdominal visceral fat accumulation.
AB  - OBJECTIVES: The purpose of this study was to investigate the possibility of
      impaired lipolysis of triglyceride-rich lipoproteins in patients with abdominal
      visceral fat accumulation by assessing two major lipolytic enzymes in the plasma,
      lipoprotein lipase (LPL) and hepatic lipase (HL). DESIGN AND PATIENTS: A total of
      31 patients [20 men, 11 women, age 50 +/- 7 years old, body mass index (BMI) 26
      +/- 2 kg/m2 (mean +/- sd)] were analyzed. Visceral fat and subcutaneous fat areas
      were evaluated using a computerized tomographic (CT) method at the level of the
      umbilicus. Total lipolytic activity in the postheparin plasma (PHP) was measured
      using Triton X-100-emulsified triolein and LPL activity was calculated as the
      activity in whole plasma inhibited by the 5D2 monoclonal antibody for LPL. LPL
      enzyme mass was determined by a sandwich enzyme immunoassay. RESULTS: The
      visceral fat area was found to be negatively correlated with LPL mass (V vs LPL
      mass, r = -0.37, P = 0.04) in PHP and had a tendency toward negative correlation
      with the LPL activity in the PHP (V vs LPL activity, r = -0.29, P = 0.12).
      Subcutaneous fat area, on the other hand, did not show any correlation with LPL
      activity (r = 0.13, P = 0.49) or mass (r = 0.22, P = 0.25) in the PHP. The
      visceral fat area was found to be positively correlated with fasting serum
      insulin levels (r = 0.67, P < 0.01). Body mass index (BMI) was not correlated
      with LPL mass or activity in the PHP. Multi-regressional analysis showed that
      abdominal visceral fat could be correlated with LPL mass in the PHP,
      independently of fasting serum insulin. The HL activity from PHP of the patients
      did not show significant correlation with visceral fat area, subcutaneous fat
      area or body mass index. CONCLUSIONS: Fat distribution affects LPL mass and
      activity, either directly or via another metabolic abnormality such as insulin
      resistance, leading to impaired hydrolysis of triglycerides in chylomicrons and
      very low density lipoproteins (VLDL) in these subjects.

PMID- 9640421
TI  - The tender neck: thyroiditis or thyroid abscess?
AB  - Following apparent subacute thyroiditis, a 16-year-old girl developed a left
      thyroid abscess thought to be secondary to steroids and haematogenous spread from
      a pilonidal abscess. The thyroid suppuration became recurrent and required
      partial thyroidectomy. Further left-sided abscess formation in the neck prompted
      a barium swallow which revealed the source of infection to be a sinus tract
      arising from the left piriform fossa. The patent fourth branchial sinus tract was
      later excised. All patients with a tender thyroid should have ultrasound-guided
      fine needle aspiration to establish the diagnosis. If suppuration is confirmed, a
      barium swallow is advised to exclude a sinus tract from the piriform fossa.

PMID- 9640422
TI  - Altered lipid pattern explains increased cardiovascular mortality in
      hypopituitary patients with growth hormone deficiency.

PMID- 9640423
TI  - Transient hypothyroidism after iodine-131 therapy for Graves' disease.

PMID- 9640424
TI  - Retinoid X receptor gamma mRNA expression is reduced in recurrent non-functioning
      pituitary adenomas.

PMID- 9640425
TI  - Voluntary and involuntary access to autobiographical memory.
AB  - Involuntary autobiographical memories recorded in a diary study are compared to
      voluntary autobiographical memories retrieved in response to verbal cues in a
      laboratory. The verbal cues were generated to be comparable to the cues that were
      found to elicit the involuntary memories. The findings demonstrate that voluntary
      and involuntary retrieval may access different samples of autobiographical
      memories. The voluntary memories were (1) less specific, (2) more frequently
      rehearsed, and (3) less emotionally positive than the involuntary memories. A
      reanalysis of the diary study examined conditions of involuntary retrieval. The
      memories occurred most frequently when attention was diffuse. They were typically
      triggered by environmental cues matching central features of the remembered
      event. The findings are discussed in relation to current models of
      autobiographical memory.

PMID- 9640426
TI  - Memory span, naming speed, and memory strategies in poor and normal readers.
AB  - Eleven-year-old severely impaired poor readers failed to show a word length
      effect with pictorial presentation, but showed an effect of equal magnitude to
      that of reading age and chronological age controls with auditory presentation.
      The lack of a pictorial word length effect was unlikely to be due to slow speed
      of naming skills, as in one study these were at least as fast as those of the
      reading age controls. It is possible that the poor readers failed to verbally
      encode the pictures. However, they reported using verbal rehearsal, and lip
      movements were often observed during presentation, suggesting that they did
      verbally encode the items. Therefore they may have failed to show a word length
      effect because they did not retrieve information from the phonological store at
      recall. Although the poor readers had impaired naming speed skills for their age
      on both discrete item identification and articulation rate tasks, they could not
      be equated with their chronological age controls on memory span or reading when
      these naming speed differences were controlled. However, the groups were matched
      on the naming speed measures when differences in reading ability were controlled.

PMID- 9640427
TI  - When even arbitrary order becomes important: developments in reliable temporal
      sequencing of arbitrarily ordered events.
AB  - By late in the first year of life, children show temporally ordered recall of
      event sequences, the orders of which are constrained by enabling relations; they
      do not reliably recall arbitrarily ordered events. Using elicited imitation, in
      two experiments, we examined age- and experience-related changes in young
      children's recall of events, the orders of which are arbitrary. The changes were
      found to have implications for the efficacy of verbal reminding and to be related
      to developments in language. Specifically, on the basis of a single experience,
      16-month-olds did not accurately recall arbitrarily ordered event sequences
      either immediately or after a two-week delay (Experiment 1); 22-month-olds
      recalled the events immediately, but not after the delay; by 28 months, children
      recalled the events even after the delay (Experiment 2A). This development was
      accompanied by changes in the ability to benefit from verbal reminders: 28-month
      olds' recall was facilitated by provision of verbal reminders, whereas that of
      the younger children was not. Moreover, age-related changes in accurate
      reproduction of lengthy arbitrarily ordered event sequences were found to be
      related to developments in language (Experiment 2B). Critically, the limitations
      on 1-year-olds' performance that are overcome with age are not absolute: After
      three experiences, 16-month-olds accurately recalled the events after a two-week
      delay; their recall was facilitated by verbal reminders (Experiment 1). The
      implications of these findings are discussed.

PMID- 9640428
TI  - Descriptiveness and proper name retrieval.
AB  - Cohen (1990) hypothesised that the retrieval of proper names is particularly
      difficult because proper names convey little information about their bearers'
      attributes. In the present study, this hypothesis was evaluated by using a face
      naming task. Faces were those of cartoon and comic-strip characters bearing
      either arbitrary names or descriptive names. Results unequivocally showed that
      retrieval blocks occurred more often in naming characters bearing arbitrary names
      than in naming characters bearing descriptive names. Moreover, retrieving
      arbitrary names that were also common names was as difficult as retrieving
      arbitrary names that were not common names. These results support Cohen's claim
      that arbitrariness plays a significant role in the relative vulnerability of
      proper name retrieval.

PMID- 9640429
TI  - Contextual dependencies during perceptual-motor skill performance: influence of
      task difficulty.
AB  - The present experiment was designed to address the role of task difficulty for
      the development of contextual-dependent behaviour during perceptual-motor task
      acquisition. Task difficulty in the present study was manipulated by restricting
      the time that the subject; (a) viewed task-relevant information, and (b) was
      afforded to execute a sequence of key presses. Assuming these manipulations made
      the acquisition of the key press tasks more difficult, it was hypothesised that
      reducing the time for either of these processes would result in a greater
      dependence on reinstating the training context at the time of test. This was
      based on previous findings reported by Wright and Shea (1991) which indicated
      that task difficulty can contribute to the development of context-dependent
      behaviour. The results of the study revealed that viewing time was a potent
      difficulty manipulation. This is supported by the slower acquisition rates for
      subjects exposed to short as opposed to long viewing conditions during training.
      More importantly, the impact of changing the intentional-incidental stimuli
      relationship that was apparent during training, during the test was greatest for
      the individuals who experienced shorter viewing times during the training phase.
      Thus, the proposed influence of task difficulty on contextual-dependent
      performance was supported. This dependency was manifested as a slowing in both
      the initiation and execution of the correct key presses. It is proposed that
      individuals trained in the more difficult viewing condition during training, when
      faced with an incongruence in the acquisition and test stimuli, must engage
      additional data-driven verification processes to supplement their extant
      knowledge in order to execute an appropriate response.

PMID- 9640430
TI  - Individual differences and the creation of false childhood memories.
AB  - We investigated if college students will create false childhood memories, the
      role of self-knowledge in memory creation, and if there are reliable individual
      differences related to memory creation. Based on information obtained from
      parents, we asked college students about several true childhood experiences. We
      also asked each student about one false event and presented the false event as if
      it was based on parent information. We asked the students to describe all events
      in two interviews separated by one day. When participants could not recall an
      event (whether true or false), we encouraged them to think about related self
      knowledge and to try to imagine the event. In an unrelated experimental session,
      the students were administered four cognitive/personality scales: the Creative
      Imagination Scale (CIS), the Tellegen Absorption Scale (TAS), the Dissociative
      Experiences Scale (DES), and the Marlowe-Crowne Social Desirability Scale (SDS).
      We found that approximately 25% of the students created false childhood memories.
      Participants who made connections to related self-knowledge in the first
      interview were more likely to create false memories. We also found that the CIS
      and the DES were positively related to memory creation. Factors that decrease
      one's ability to engage in reality monitoring are related to the acceptance of
      false events and the creation of false memories.

PMID- 9640431
TI  - Rehabilitation of memory for people's names.
AB  - In a training study, memory-impaired patients were taught strategies to improve
      the learning of new names and the retrieval of familiar people's names. To
      improve new name learning, the patients were encouraged to give more meaning to a
      person's name, without requiring an explicit association between the face and the
      name. Strategies to improve retrieval of familiar names mainly concerned ways to
      resolve tip-of-the-tongue states. Learning names to faces improved following
      training on one of the two target tests and this improvement was maintained six
      months following training. Retrieval of familiar people's names also improved
      immediately following the training, although the improvement disappeared at the
      six-month follow-up. Two control memory tests and a group of normal subjects, who
      received no training, were used to discriminate an effect of training from the
      effects of repeated testing and the extensive attention received by the trained
      group.

PMID- 9640432
TI  - The spacing effect depends on an encoding deficit, retrieval, and time in working
      memory: evidence from once-presented words.
AB  - The spacing effect in list learning occurs because identical massed items suffer
      encoding deficits and because spaced items benefit from retrieval and increased
      time in working memory. Requiring the retrieval of identical items produced a
      spacing effect for recall and recognition, both for intentional and incidental
      learning. Not requiring retrieval produced spacing only for intentional learning
      because intentional learning encourages retrieval. Once-presented words provided
      baselines for these effects. Next, massed and spaced word pairs were judged for
      matches on their first three letters, forcing retrieval. The words were not
      identical, so there was no encoding deficit. Retrieval could and did cause
      spacing only for the first word of each pair; time in working memory, only for
      the second.

PMID- 9640433
TI  - Apperception and imagery in blindfold chess.
AB  - Apperception constructs functional and "meaningful" mental representations. These
      representations are often built on mental images. Hence it is rational to assume
      that the contents of some parts of images may be functionally more important than
      others. This means that the cognitive processing of some parts of the image is
      more effective than for others. To extract this preferential structure, which we
      call the functional figure in mental images, five experiments were conducted on
      blindfold chess imagery. We showed that blindfold chess players have much better
      recall of functionally significant than of functionally insignificant areas of
      chess positions. Thus, of the various mental representations of chess board
      areas, the functionally more significant areas are better represented than
      others.

PMID- 9640434
TI  - Visuo-spatial imagery in congenitally totally blind people.
AB  - The present study provides evidence for congenitally blind people's ability to
      generate visuo-spatial images, and explores its limitations. Congenitally blind
      and sighted participants were asked to memorize the spatial positions of target
      objects (cubes) in two- and three-dimensional matrices, while simultaneously
      performing a sequence of spatially based imagery operations. Furthermore, during
      half of the trials, subjects were required to perform an articulatory suppression
      task. Although articulatory suppression affected both groups to the same extent,
      congenitally blind people performed poorly with more demanding spatial tasks and
      when an active elaboration was required.

PMID- 9640435
TI  - Knowledge of the crime context: improving the understanding of why the cognitive
      interview works.
AB  - Since the Cognitive Interview (CI) was devised under laboratory conditions
      (Geiselman, Fisher, MacKinnon, & Holland, 1985), researchers have performed many
      experiments where a variety of variables and conditions have been reported.
      Nevertheless, few studies have attempted to delve into the theoretical aspects on
      which the CI is based. A variable that might help us to improve our understanding
      of why the CI works is prior knowledge of the crime context. Some studies have
      included familiar contexts and others unfamiliar ones, but no study has been
      performed to test the effect of the familiarity of the crime context as an
      independent variable. The aim of this research is to study the effect of prior
      knowledge on subjects' memory when they are interviewed by means of the CI in
      contrast to a Spanish Standard Interview (SSI). A significant effect of prior
      knowledge that subjects had of the context where the crime took place was
      expected, especially for those subjects who were interviewed by means of the CI.
      Results confirmed this hypothesis.

PMID- 9640436
TI  - Diabetic retinopathy.
AB  - Diabetic retinopathy is the commonest cause of blindness amongst individuals of
      working age. The onset of retinopathy is variable. Regular ophthalmic screening
      is essential in order to detect treatable lesions early. Retinal laser therapy is
      highly effective in slowing the progression of retinopathy and in preventing
      blindness. As the sufferers of diabetes mellitus, the commonest endocrine
      disorder, now constitute approximately 1-2% of Western populations, concerted
      multidisciplinary effort must be made towards cost-effective community screening
      by the medical community.

PMID- 9640437
TI  - Disorders of the sleep-wake cycle in adults.
AB  - Adults have an intrinsic body clock which regulates a complex series of rhythms
      including sleep and wakefulness, fatigue and cognitive ability. This endogenous
      clock naturally runs more slowly than the solar day and is entrained to a 24-h
      rhythm primarily by the alternation of light and darkness. Jet lag, shift-work
      sleep disorder, and some of the chronic insomnias are caused by a temporal
      discrepancy of the body clock relative to the surrounding environment and social
      network. The underlying mechanisms and general management are described. Both
      bright light and melatonin therapy have potential in the management of these
      disorders. Traditionally, bright light therapy has been used to alleviate the
      depression associated with seasonal affective disorder. Melatonin has received
      much ill-formed publicity, it being claimed that it is a panacea and an
      'antiageing' treatment. Both of these treatment approaches are reviewed.

PMID- 9640438
TI  - Thymectomy for myasthenia gravis.
AB  - The pathophysiological role of the thymus in myasthenia gravis, and the mechanism
      of therapeutic effect of thymectomy, are incompletely understood. Nevertheless,
      thymectomy is a valuable treatment modality in selected patients with generalised
      myasthenia gravis. There are several types of thymectomy operation, but no one
      operative approach is clearly superior to the others. Total removal of the thymus
      gland is essential. Additional excision of associated mediastinal and cervical
      tissue, that may harbor ectopic thymic rests, is a controversial surgical issue.
      Surgeons that advocate thymectomy through small, cosmetically favourable,
      incisions usually believe that simple removal of the thymus gland is an adequate
      operation. Surgeons that emphasise the importance of removing extrathymic tissue,
      in addition to the thymus gland, usually favour greater operative exposure
      through a median sternotomy. To minimise operative morbidity, surgery for
      myasthenia gravis requires a multidisciplinary (neurology, surgery, anaesthesia)
      approach to peri-operative care.

PMID- 9640440
TI  - Advance directives and living wills.
AB  - Under certain circumstances, living wills or advance directives may carry legal
      force in the UK. This paper traces the development of advance directives,
      clarifies their current legal position and discusses potential problems with
      their use. Case histories are used to illustrate some of the common dilemmas
      which doctors may face.

PMID- 9640441
TI  - Recognition and management of hypercholesterolaemia in patients awaiting elective
      coronary artery bypass grafting.
AB  - The recently published Scandinavian Simvastatin Survival Study showed that long
      term treatment with simvastatin, in patients with ischaemic heart disease and
      serum cholesterol levels between 5.5 and 8.0 mmol/l, improved survival. The
      present study was conducted in order to evaluate whether patients with ischaemic
      heart disease awaiting coronary revascularisation are aware of their serum
      cholesterol levels and whether raised levels are being treated adequately. One
      hundred consecutive patients admitted from our waiting list for elective coronary
      artery bypass grafting, with or without valve replacement, were included in the
      study. The patients were asked whether they had a history of raised serum
      cholesterol and, if so, how this was being treated. Fasting serum cholesterol
      levels were subsequently taken in the morning before surgery. Forty-six patients
      gave a positive history of raised blood cholesterol levels; 25 of these were on
      cholesterol-lowering medication at the time of admission, 15 were on a lipid
      lowering diet and six were not being treated. Thirty-one (67%) of these 46
      patients had a serum cholesterol of more than 5.5 mmol/l, compared with 30 (56%)
      of the 54 patients without a positive history of hypercholesterolaemia, and 61%
      of the total 100 patients. These data suggest that an inadequate number of
      patients awaiting coronary artery bypass grafting are aware of their cholesterol
      status. The management of hypercholesterolaemia among these patients could be
      improved.

PMID- 9640439
TI  - Trends in the management of gastro-oesophageal reflux disease.
AB  - Gastro-oesophageal reflux disease is common, with up to 10% of the general
      population experiencing heartburn on a daily basis. It is a chronic condition and
      follow-up studies indicate the presence of symptoms at least 20 years after
      initial diagnosis. In addition to lifestyle modifications, management usually
      involves the use of an acid suppressant from the H2-receptor antagonist or proton
      pump inhibitor groups or a prokinetic agent at some stage. In terms of initial
      symptom resolution and mucosal healing the proton pump inhibitors are
      consistently superior to the other available agents. However, while it is
      possible to keep the majority of patients in remission while taking medications,
      almost all patients have a recurrence of symptoms within six months of stopping
      medications. The introduction of laparoscopic fundoplication has produced
      promising initial results but the long-term benefits of this procedure remain to
      be established. The role of Helicobacter pylori eradication in the management of
      gastro-oesophageal reflux disease needs further evaluation.

PMID- 9640442
TI  - Variability in management of symptomless microhaematuria in schoolchildren.
AB  - The evaluation of incidentally detected symptomless microhaematuria in
      schoolchildren is controversial. Some authors advocate varying numbers of
      immediate tests, while others recommend investigations only in cases who develop
      systemic symptoms or signs, or a decline in renal function. The objective of this
      study was to estimate the extent to which this uncertainty affects the declared
      habits of practising physicians. A sample of 16 family physicians, 42 primary
      care paediatricians and 26 full-time hospital-based paediatric nephrologists in
      Israel were asked to complete a survey using a written case of a hypothetical
      eight-year-old boy with incidentally detected symptomless microhaematuria.
      Responses were received from 16 (100%), 18 (43%) and 18 (69%), respectively. The
      mean number of requested tests, other than follow-up examination of the urine,
      were 1.5 (range 0-5) for family physicians, 2.5 (1-5) for primary care
      paediatricians and 5.3 (2-12) for paediatric nephrologists, at an average cost of
      NIS 408 (US$ 136), NIS 454 (US$ 151) and NIS 860 (US$ 286), respectively. There
      was also a marked variability within subspecialty groups, so that some family
      physicians recommended more tests at a higher cost than some of the paediatric
      nephrologists. There was a marked and unexplained variability within and among
      the three groups of respondents regarding the extent of the evaluation. The main
      reason for this variability is probably the uncertainty about the scientifically
      appropriate way to approach this condition in a symptomless child.

PMID- 9640443
TI  - A collaborative audit of the management of hypertension in general practice.
AB  - We carried out an audit of the management of essential hypertension in general
      practice, against standards based on current guidelines. We examined the records
      of 882 hypertensive subjects (on medication) in whom hypertension had been
      diagnosed between January 1989 and December 1993, from 14 general practices in
      the Portsmouth and South East Hampshire Health Authority. The overall prevalence
      of hypertension was 3.5%. Pretreatment blood pressure had been measured on three
      or more occasions in 87% of patients. Pretreatment blood pressure was equal to or
      greater than 150/95 mmHg in 96% and 160/100 mmHg in 86.5% of patients. A thiazide
      diuretic was the initial drug of choice in 30% of patients, with beta-blockers
      being the most popular initial treatment. Ninety per cent of patients had had
      their blood pressure measured at least once during the preceding year. In 82.5%
      of patients, current blood pressure was less than 150/95 mmHg, while 44% achieved
      a current blood pressure less than 140/90 mmHg. We conclude that the prevalence
      of hypertension in this population was lower than expected, suggesting the need
      for improved screening. We also propose that the initial treatment choice should
      be a thiazide in the majority, which would result in significant cost saving. The
      blood pressure control was suboptimal compared to current guidelines.

PMID- 9640444
TI  - Lymphogranuloma venereum as a cause of rectal strictures.
AB  - Rectal strictures are uncommon in young patients without a history of malignancy,
      inflammatory bowel disease or previous surgery. Lymphogranuloma venereum of the
      rectum has been described as a rare cause of rectal strictures in the western
      world, mainly in homosexual men and in blacks. It presents with nonspecific
      symptoms, rectal ulcer, proctitis, anal fissures, abscesses and rectal
      strictures. Clinical and endoscopic findings as well as histology resemble
      Crohn's disease, which may be misdiagnosed. Serology is often positive for
      Chlamydia trachomatis but negative serology is not uncommon. We present two young
      black women who suffered from chronic diarrhoea, abdominal pain and weight loss.
      There was no previous history and investigations showed in both cases a long
      rectal stricture. Serology was positive in one patient. They were treated with
      erythromycin and azithromycin and they both underwent an anterior resection of
      the rectum. Postoperative histology confirmed the presence of lymphogranuloma
      venereum of the rectum. We conclude that rectal lymphogranuloma venereum is a
      rare cause of rectal strictures but surgeons should be aware of its existence and
      include it in the differential diagnosis of unexplained strictures in high-risk
      patients.

PMID- 9640445
TI  - Giant cell arteritis presenting as renal vasculitis.
AB  - Giant cell arteritis commonly presents with headache, polymyalgia, and visual
      signs and symptoms. Other neurological, respiratory or vascular symptoms occur in
      10-30% of patients. It is extremely rare for giant cell arteritis to present
      initially with haematuria. Here we describe a case which presented with fever and
      haematuria, which emphasise the need to be vigilant about the diagnosis of giant
      cell arteritis as an underlying cause.

PMID- 9640446
TI  - Sarcoidosis of the paranasal sinuses treated with hydroxychloroquine.
AB  - A case of sarcoidosis of the paranasal sinuses is reported. Biopsies of the sinus
      mucosa showed typical noncaseating granulomas. Hydroxychloroquine, which is known
      to be active on the cutaneous form of sarcoidosis, was used here with success and
      is proposed as an effective alternative to high-dose systemic steroids.

PMID- 9640447
TI  - A rare abdominal cystic mass with unusual presentation.

PMID- 9640448
TI  - An unusual cause for a painful diplopia.

PMID- 9640449
TI  - Spontaneous intercostal bulge.

PMID- 9640451
TI  - Abdominal pain in a healthy young man.

PMID- 9640450
TI  - Mycobacterial liver abscess in a patient with AIDS.

PMID- 9640452
TI  - An 88-year-old woman with tetraparesis after a fall.

PMID- 9640453
TI  - An unusual abdominal mass.

PMID- 9640454
TI  - Acute psychosis in a trauma patient due to ciprofloxacin.

PMID- 9640455
TI  - Bacterial endocarditis.

PMID- 9640456
TI  - Perforated diverticulitis following extra-abdominal surgery.

PMID- 9640457
TI  - Role of lipid metabolites in the signalling and activation of macrophage cells by
      lipopolysaccharide.

PMID- 9640458
TI  - Chemistry and functional distribution of sulfoglycolipids.

PMID- 9640459
TI  - Oregon groups devise rules, policies on assisted suicide.

PMID- 9640460
TI  - Medicaid to pay Mississippi pharmacists for disease management.

PMID- 9640461
TI  - FDA proposes rules for health claims on dietary supplements.

PMID- 9640462
TI  - Immediate use of anticoagulants may not improve stroke outcomes.

PMID- 9640464
TI  - Teen smoking up one third.

PMID- 9640463
TI  - Integrated systems may have economic incentive for using alteplase in stroke
      patients.

PMID- 9640465
TI  - Herbals and homeopathic remedies as formulary items?

PMID- 9640466
TI  - Outcomes of antiemetic therapy after the administration of high-dose
      antineoplastic agents.
AB  - Patterns of antiemetic therapy and its outcomes in patients undergoing high-dose
      antineoplastic therapy were studied. The study, conducted at a cancer center,
      included both a retrospective evaluation of patients undergoing highly emetogenic
      high-dose chemotherapy with peripheral blood stem-cell rescue between November
      1994 and December 1995 and a concurrent evaluation of patients treated between
      January and May 1996. During the study period the recommended antiemetic regimen
      for highly emetogenic chemotherapy was a single dose of granisetron 1 mg i.v.
      daily 30 minutes before treatment on days of chemotherapy. Severity of nausea and
      vomiting during both the acute phase (from day 1 of chemotherapy to 24 hours
      after its completion) and delayed phase (from 24 hours to five days after the end
      of chemotherapy) was graded according to the Common Toxicity Criteria Grading
      Scale. A total of 59 patients were evaluable; 41 were reviewed retrospectively,
      and 18 were reviewed concurrently. On day 1 of the acute phase, 53 patients (90%)
      had no vomiting and 51 patients (86%) had no nausea. The frequency and severity
      of nausea and vomiting increased on successive acute-phase days, and it was
      necessary to add other antiemetics. Nausea and vomiting continued to be
      significant problems throughout the delayed phase; 32 (54%) of the patients had a
      maximum of grade 3 nausea, and 29 patients (49%) had a maximum of grade 2
      vomiting. Substantial numbers of patients who received selective serotonin type 3
      receptor antagonists before high-dose antineoplastic agents had significant
      nausea and vomiting that required the addition of other antiemetics.

PMID- 9640467
TI  - Effect of a pharmacist-education initiative on ketorolac use and costs in a
      Medicaid program.
AB  - The effects of a pharmacist-education initiative on the use and costs of
      ketorolac in a state Medicaid program are reviewed. An intervention letter
      describing changes in the manufacturer's prescribing guidelines for ketorolac and
      providing suggestions for interacting with physicians regarding the use of
      ketorolac was sent to 150 of the 301 pharmacies that participate in New Mexico's
      Medicaid program. The remaining 151 pharmacies served as a control group.
      Ketorolac claims records for three months before and after the intervention were
      reviewed. The mean quantity of ketorolac tablets, total days' supply, and number
      of prescriptions filled per pharmacy per month were calculated for both periods.
      The number of prescriptions not filled as a result of the intervention as well as
      the number that could have been avoided, the number of cases of peptic ulceration
      (ketorolac's major adverse effect) that would be avoided, and the associated cost
      savings if all the state's Medicaid pharmacies had been included in the
      intervention were estimated. A total of 167 pharmacies (90 intervention and 77
      control) dispensed ketorolac for Medicaid patients during the study period.
      Ketorolac dispensing rates declined during the postintervention period in both
      the intervention group and the control group, but the reduction was greater in
      the intervention group. It was predicted that if all pharmacies were included in
      an intervention, 135.6 fewer prescriptions for ketorolac would be filled each
      year; as a result, 1.14 cases of peptic ulceration would be avoided and net
      Medicaid costs would be reduced by $1638. Sending educational letters to
      pharmacists was associated with a modest reduction in ketorolac use in a state
      Medicaid program; a net reduction in Medicaid costs if the intervention were
      extended to all pharmacies that participate in the state's Medicaid program was
      projected.

PMID- 9640468
TI  - Motivations and practice-area preferences of pharmacists interested in pursuing a
      Pharm.D. degree through a nontraditional program.
AB  - Pharmacists' interest in a proposed nontraditional Pharm.D. program, motivations
      for wanting to pursue a Pharm.D. degree, and practice-area preferences were
      surveyed. Questionnaires were mailed to 12,621 pharmacists in Illinois and
      Arizona. Information sought included current position and practice area, number
      of job and career changes, preferred practice area, and interest in enrolling in
      a proposed nontraditional Pharm.D. program described in a cover letter. For
      pharmacists indicating an interest, information was sought on motivations for
      wanting to pursue a Pharm.D. degree expected support from employers, and
      preferred practice areas after obtaining a Pharm.D. degree. The response rate was
      28.8%. A total of 1119 respondents (31.9%) indicated that they would or probably
      would enroll in the proposed Pharm.D. program. These pharmacists gave improving
      their clinical skills and improving the quality of their work as reasons for
      wanting to enroll, and half indicated that their current practice area would be
      their preferred area after they completed a Pharm.D. degree. Almost three
      quarters (72%) of hospital pharmacists; more than 60% of home health care or
      consultant independent, and managed care pharmacists; and 21% of pharmacists in
      chain pharmacies stated a preference to stay in their current practice area after
      obtaining a Pharm.D. degree. Eight variables were useful in predicting whether
      respondents would prefer to remain in their current practice area, including
      tuition assistance or reimbursement from employers, satisfaction with current
      position, and number of years in current position. Respondents who were
      interested in pursuing a Pharm.D. degree through the nontraditional program
      described to them were motivated by a desire to improve their clinical skills and
      the quality of their work and the opportunity to open doors to new careers.

PMID- 9640469
TI  - Effect of sodium metabisulfite on hydrogen peroxide production in light-exposed
      pediatric parenteral amino acid solutions.
AB  - The effect of sodium metabisulfite (MBS) on hydrogen peroxide (HP) production in
      model and commercial amino acid solutions exposed to phototherapy light was
      studied. Model and commercial pediatric amino acid solutions were prepared such
      that the amino acid concentration was 1%. MBS concentration, riboflavin
      concentration, and duration of exposure to phototherapy light were varied to
      determine the effect on HP production. Control solutions were kept in the dark.
      HP production was assayed in the model amino acid solutions by using potassium
      iodide in the presence of ammonium molybdate. In all experiments, HP production
      was measured at 360 nm in the presence and absence of catalase. In light-exposed
      solutions, HP production increased linearly for several hours and reached a
      plateau by eight hours. A mean maximum of 940 microM was produced (data pooled
      for all solutions). No detectable HP was generated in the solutions kept in the
      dark. After two hours of light exposure, it was necessary to add at least 10
      times more MBS than is typically found in commercial total parenteral nutrient
      solutions to scavenge all the HP produced. An average of up to 940 microM of HP
      was produced in model and commercial pediatric parenteral 1% amino acid solutions
      in the presence of phototherapy light and clinically relevant concentrations of
      riboflavin and MBS. Light exposure decreased the antioxidant effect of MBS.

PMID- 9640470
TI  - Pharmacy coordination of an indigent care program in a psychiatric facility.

PMID- 9640471
TI  - Activity of enoxaparin sodium in tuberculin syringes for 10 days.

PMID- 9640472
TI  - Content uniformity and stability of nifedipine in extemporaneously compounded
      oral powders.

PMID- 9640473
TI  - Institutional and contingency approaches to the reprofessionalization of
      pharmacy.

PMID- 9640474
TI  - Therapeutic drug monitoring: observations and recommendations.

PMID- 9640475
TI  - Workshop for developing drug formularies in Russia.

PMID- 9640476
TI  - Filtration recommendations for i.v. medications.

PMID- 9640477
TI  - Fluorouracil precipitate.

PMID- 9640478
TI  - Fluorouracil precipitate.

PMID- 9640479
TI  - Comparison of tacrolimus absorption in transplant patients receiving continuous
      versus interrupted enteral nutritional feeding.
AB  - OBJECTIVE: To determine the effect of enteral nutritional feeding on the
      absorption of tacrolimus administered through a nasoduodenal tube to organ
      transplant patients. METHODS: A nonrandomized, prospective study of tacrolimus
      absorption was performed in 10 liver or lung transplant patients who received
      Osmolite enteral nutrition through a nasoduodenal feeding tube. Multiple blood
      samples were collected just prior to and at 30 minutes, 1, 2, 3, 4, 6, 8, 10, and
      12 hours after nasoduodenal administration of tacrolimus on 2 consecutive days,
      once when tacrolimus was administered along with the continuous enteral feeding
      and the other time when the enteral feeding was withheld 1 hour prior to and 8
      hours after tacrolimus administration, to assess tacrolimus absorption. The whole
      blood tacrolimus concentrations were measured by the microparticulate enzyme
      immunoassay method. Pharmacokinetic parameters between the two time periods were
      compared by using a paired t-test at a significance level of a p value of 0.05 or
      less. RESULTS: The time to reach peak blood concentrations (p = 0.055), dose
      normalized trough concentrations (p = 0.617), maximum blood concentrations (p =
      0.197), and dose-normalized AUC (p = 0.755) were not significantly different
      between two study periods. CONCLUSIONS: This study demonstrated that simultaneous
      administration of Osmolite enteral feedings with tacrolimus did not interfere
      with tacrolimus absorption in transplant patients.

PMID- 9640480
TI  - Management of patients with type 2 diabetes by pharmacists in primary care
      clinics.
AB  - OBJECTIVE: To determine the impact of clinical pharmacists involved in direct
      patient care on the glycemic control of patients with type 2 diabetes mellitus.
      DESIGN: Eligible patients included those with type 2 diabetes who received
      insulin or were initiated on insulin therapy by the pharmacists and were willing
      to perform self-monitoring of blood glucose. The pharmacists provided diabetes
      education, medication counseling, monitoring, and insulin initiation and/or
      adjustments. All initial patient interactions with the pharmacists were face-to
      face. Thereafter, patient-pharmacist interactions were either face-to-face or
      telephone contacts. SETTING: Two primary care clinics in a university-affiliated
      Veterans Affairs Medical Center. PARTICIPANTS: Study subjects were patients with
      type 2 diabetes who were referred to the pharmacists by their primary care
      providers for better glycemic control. OUTCOME MEASURES: Primary outcome
      variables were changes from baseline in glycosylated hemoglobin, fasting blood
      glucose, and random blood glucose measurements. Secondary outcomes were the
      number and severity of symptomatic episodes of hypoglycemia, and the number of
      emergency room visits or hospitalizations related to diabetes. Twenty-three
      veterans aged 65-9.4 years completed the study. Fifteen (65%) patients were
      initiated on insulin by the pharmacists; 8 (35%) were already using insulin.
      Patients were followed for a mean-SD of 27-10 weeks. Glycosylated hemoglobin,
      fasting blood glucose concentrations, and random blood glucose concentrations
      significantly decreased from baseline by 2.2% (p = 0.00004), 65 mg/dL (p < 0.01),
      and 82 mg/dL (p = 0.00001), respectively. Symptomatic hypoglycemic episodes
      occurred in 35% of patients. None of these episodes required physician
      intervention. CONCLUSIONS: This study demonstrates that pharmacists working as
      members of interdisciplinary primary care teams can positively impact glycemic
      control in patients with type 2 diabetes requiring insulin.

PMID- 9640481
TI  - State pharmacy regulators' opinions on regulating pharmaceutical care outcomes.
AB  - OBJECTIVE: To examine the opinions of state pharmacy regulators regarding
      responsibility for the outcomes of drug therapy, and approaches that might be
      taken to regulate for pharmaceutical care outcomes. DESIGN: Surveys were sent to
      the executive secretaries of state pharmacy boards. The executive secretaries
      were encouraged to seek input from other board staff and board members in
      formulating a response. Reminder postcards were sent to all subjects 1 week after
      the initial mailing. MEASURES: The survey instrument was divided into three
      sections. The first section identified 10 approaches that state boards could use
      to regulate for outcomes and asked subjects to indicate the utility of each. The
      second and third sections asked the subjects to determine the extent to which
      pharmacies and pharmacists, respectively, should be responsible for outcomes
      potentially related to pharmaceutical care. RESULTS: Forty-one usable surveys
      were returned. All approaches to regulation were viewed as potentially useful,
      and scores for three approaches indicated that they would be consistently helpful
      for effective regulation of pharmaceutical care outcomes. The pharmacy was viewed
      as solely responsible for poor outcomes related to systems deficiencies, a lack
      of self-assessment, inadequate references, equipment, and technician support.
      Pharmacists were assigned greatest responsibility for outcomes related to
      prescription filling, and less responsibility for outcomes related to patient
      care. However, there was considerable variation in responses to many of the
      items, reflecting the diverse opinions of pharmacy regulators on these issues.
      CONCLUSIONS: While pharmacy regulators appear open to some outcomes-oriented
      approaches to regulation, there is no clear consensus on responsibility for
      pharmaceutical care outcomes.

PMID- 9640482
TI  - Syncopal episodes associated with cisapride and concurrent drugs.
AB  - OBJECTIVE: To report a case of QT prolongation and syncopal episodes resulting
      from concomitant use of cisapride and agents known to inhibit its metabolism.
      CASE SUMMARY: A 53-year-old white woman was involved in two motor vehicle
      accidents on the same day after experiencing syncopal episodes. Cardiac and
      neurologic evaluations were negative; the syncopal episodes were attributed to QT
      prolongation associated with the concomitant use of cisapride and agents known to
      inhibit its metabolism. DISCUSSION: This is the first case published in the
      English-language literature describing QT prolongation resulting from the
      concomitant use of cisapride and agents known to inhibit its metabolism.
      Clarithromycin inhibits CYP3A4, the isoenzyme responsible for the metabolism of
      cisapride. Concomitant administration of cisapride with agents known to inhibit
      CYP3A4 (i.e., azole antifungals, erythromycin, clarithromycin) may result in
      elevated cisapride concentrations. Elevated cisapride concentrations have been
      associated with QT prolongation, syncopal episodes, and cardiac dysrhythmias.
      CONCLUSIONS: Acquired QT prolongation is a well-recognized adverse effect of
      several drugs. Recognition of newer drugs and drug combinations that place
      patients at risk for this potentially fatal adverse event is imperative for
      appropriate monitoring and prevention.

PMID- 9640483
TI  - Cutaneous ulceration: an unusual sign of methotrexate toxicity--first report in a
      patient without psoriasis.
AB  - OBJECTIVE: To describe a case of skin ulcer related to methotrexate toxicity.
      CASE SUMMARY: A 67-year-old white man with seronegative arthralgia developed
      recurrent skin ulcer concurrent with 3-year treatment with methotrexate 5 mg
      daily. The skin ulcer resolved on discontinuation of methotrexate. DISCUSSION: To
      the best of our knowledge, this is the first reported case of skin ulcer believed
      to be induced by methotrexate in a patient without psoriasis. CONCLUSIONS: Skin
      ulceration should be added to the list of possible toxic adverse effects of
      methotrexate, not only in psoriatic patients but also in those without psoriasis.

PMID- 9640484
TI  - Respiratory depression following administration of intrathecal bupivacaine to an
      opioid-dependent patient.
AB  - OBJECTIVE: To document two cases of respiratory depression in patients receiving
      morphine once the stimulating effect of pain on respiration was removed by
      bupivacaine. CASE SUMMARIES: Case 1: A 72-year-old 84-kg white man with cancer of
      the bladder and bone metastases had intense back and leg pain that was treated
      with intrathecal morphine for 6 months at an increasing dosage up to 10 mg twice
      daily. The intrathecal route was avoided for 4 days because of a suspected local
      infection at the site of the intrathecal catheter. During this 4-day period the
      patient received extended-release morphine and subcutaneous morphine daily. When
      the intrathecal route was used again, he received an identical dose of morphine
      plus bupivacaine and epinephrine. Ten minutes after the injection, fatal
      respiratory distress occurred. Case 2: A 92-year-old white woman was admitted for
      revascularization of arteritis on her left leg. To treat a painful sacrum and
      heel bedsores, she received extended-release oral morphine for 8 days. Induction
      of the intrathecal anesthesia was performed with bupivacaine. After 10 minutes,
      the patient became subcomatose, with miosis and apnea. Intravenous naloxone
      restored spontaneous respiration and normal consciousness. CONCLUSIONS: Pain is a
      physiologic antagonist of the respiratory depressant effects of opioid
      analgesics. By reducing pain stimulation, bupivacaine may make patients more
      susceptible to opioid respiratory depression. Such situations require titration
      of bupivacaine and other analgesics as well as increased monitoring of the
      patient.

PMID- 9640485
TI  - Probable diltiazem-induced acute interstitial nephritis.
AB  - OBJECTIVE: To describe a case of acute interstitial nephritis (AIN) probably
      related to administration of diltiazem. CASE SUMMARY: A 53-year-old white man
      presented to the hospital experiencing abdominal pain radiating to both renal
      fossae, as well as dysuria. Diltiazem and atenolol had been prescribed to treat
      an episode of precordial pain associated with effort. An erythematous
      maculopapular rash developed approximately 2 hours after administration of a
      single dose of diltiazem, and acute renal failure, associated with elevated liver
      function test results, developed 6 days later. DISCUSSION: To the best of our
      knowledge, this is the third reported case of acute renal failure believed to be
      induced by diltiazem. In all cases, there was an obvious temporal relationship
      between administration of diltiazem and the onset of acute renal failure.
      Previous reports failed to discuss a probable pathogenic mechanism. AIN is the
      most likely etiology of acute renal failure in our patient. Favorable resolution
      with no relapse, the presence of the skin rash, and the liver sequelae suggest a
      common immunoallergic mechanism. CONCLUSIONS: Healthcare professionals should
      consider diltiazem-induced AIN in the differential diagnosis of a patient taking
      diltiazem who develops acute renal failure.

PMID- 9640486
TI  - Mibefradil: a new class of calcium-channel antagonists.
AB  - OBJECTIVE: To describe the pharmacology, pharmacokinetics, and clinical efficacy
      of mibefradil compared with other agents used for hypertension and angina. DATA
      SOURCES: A MEDLINE search was performed for the period of January 1980 through
      September 1997 using the key terms mibefradil or Ro 40-5967. All articles written
      in English were considered for review. STUDY SELECTION AND DATA EXTRACTION: All
      clinical studies involving mibefradil were evaluated. Preclinical data were
      included if these data were not adequately represented in clinical (human)
      studies. DATA SYNTHESIS: Mibefradil is the first member of a new class of calcium
      channel antagonists (CCAs) that block the T-type calcium channels. A long
      elimination half-life makes once-daily dosing feasible, and the drug's lack of
      negative inotropy and reflex tachycardia distinguishes it from other available
      CCAs. When administered at recommended dosages (50 or 100 mg once daily),
      mibefradil reduces blood pressure over 24 hours in patients with hypertension,
      improves exercise capacity, and relieves anginal symptoms in patients with
      chronic stable angina pectoris. CONCLUSIONS: Clinical studies have found that the
      antihypertensive effects of mibefradil are comparable with those of nifedipine,
      verapamil, and amlodipine, and more effective than those of diltiazem. These
      effects result from peripheral vasodilation and a slight reduction in heart rate.
      Selective vasodilation of the coronary vasculature makes it an effective
      antianginal agent when used alone or added to beta-blocker therapy. Mibefradil
      demonstrates no significant effects on cardiac contractility, and no adrenergic
      stimulation resulting in reflex tachycardia. Therefore, it may have some
      advantages over currently available CCAs, especially in patients with congestive
      heart failure, although such advantages are unproven in published clinical
      trials. Ongoing clinical studies, including the Mortality Assessment in
      Congestive Heart Failure Trial (MACH-1) currently in progress, are needed to
      clarify mibefradil's place in cardiovascular therapy.

PMID- 9640487
TI  - Ranitidine bismuth citrate in the treatment of Helicobacter pylori infection and
      duodenal ulcer.
AB  - OBJECTIVE: To review the clinical pharmacology of ranitidine bismuth citrate in
      the treatment of Helicobacter pylori (HP) infection and duodenal ulcer. DATA
      SOURCES: A MEDLINE search of the English-language literature from 1992 to January
      1997 was conducting using the key terms Tritec, ranitidine, and bismuth.
      References of articles pertaining to treatment of duodenal ulcer or HP were
      extensively searched for relevant sources. DATA EXTRACTION: All articles
      pertaining to ranitidine bismuth citrate were considered for inclusion, with
      emphasis placed on randomized, double-blind trials. Priority was placed on data
      pertaining to regimens that are currently approved by the Food and Drug
      Administration for the treatment of duodenal ulcer in conjunction with HP. DATA
      SYNTHESIS: Each tablet of ranitidine bismuth citrate 400 mg contains 162 mg of
      ranitidine base, 128 mg of trivalent bismuth, and 110 mg of citrate. It uses the
      acid-suppressive actions of ranitidine and the antimicrobial and mucosal
      protective effects of bismuth to eradicate HP. Ranitidine bismuth citrate in
      conjunction with clarithromycin represents one of four treatment regimens
      currently approved in the US for duodenal ulcer associated with HP infection. In
      four double-blind, randomized trials, this agent has achieved HP eradication
      rates of 73-94% and duodenal ulcer healing rates of 73-89%. It is given twice
      daily for 28 days, and is associated with very low rates of adverse effects.
      CONCLUSIONS: Relative to some therapeutic alternatives, ranitidine bismuth
      citrate plus clarithromycin may be simpler to take and have less adverse effects,
      but may be more expensive. Compared with omeprazole plus clarithromycin, it is
      less expensive, may have lower ulcer healing rates, but may be more effective in
      eradicating HP. The role of ranitidine bismuth citrate will continue to evolve as
      more patients are treated, and other regimens continue to be tested for duodenal
      ulcer healing and HP eradication.

PMID- 9640488
TI  - Beyond benzodiazepines: alternative pharmacologic agents for the treatment of
      insomnia.
AB  - OBJECTIVE: To review the epidemiology, etiology, and classification of insomnia
      and provide an overview of the pharmacologic therapy of insomnia. Novel
      nonbenzodiazepine hypnotics including zolpidem, zopiclone, and zaleplon, as well
      as nonprescription products such as valerian and melatonin, are reviewed in
      detail. DATA SOURCES: A MEDLINE search was performed to identify relevant
      clinical studies, case reports, abstracts, and review articles published between
      April 1992 and December 1997. Key search terms included insomnia,
      benzodiazepines, zolpidem, zopiclone, zaleplon, Cl 284,846, melatonin, and
      valerian. Additional references were obtained from the lists of review articles
      and textbooks. DATA EXTRACTION AND SYNTHESIS: Data concerning the safety and
      efficacy of the hypnotic agents were extracted from all available clinical trials
      and abstracts. Background information regarding insomnia, benzodiazepines, and
      other hypnotics was extracted from the most current literature, including review
      articles and textbooks. CONCLUSIONS: New developments in benzodiazepine receptor
      pharmacology have introduced novel nonbenzodiazepine hypnotics that provide
      comparable efficacy to benzodiazepines. Although they may possess theoretical
      advantages over benzodiazepines based on their unique pharmacologic profiles,
      they offer few, if any, significant advantages in terms of adverse effects. Over
      the-counter agents such as valerian and melatonin may be useful in alleviating
      mild, short-term insomnia, but further clinical trials are required to fully
      evaluate their safety and efficacy.

PMID- 9640489
TI  - Selective serotonin-reuptake inhibitor-induced movement disorders.
AB  - OBJECTIVE: To compile and evaluate all available data suggesting an association
      between selective serotonin-reuptake inhibitor (SSRI) administration and the
      occurrence of movement disorders, and to characterize these reactions in terms of
      onset, duration, treatment and outcome, and potential predisposing factors.
      METHODOLOGY: Reports of movement disorders were identified by conducting a
      comprehensive literature search that included tertiary adverse drug reaction
      resources, MEDLINE, EmBASE, Biological Abstracts, Current Contents, Reactions,
      ClinAlert, and International Pharmaceutical Abstracts. In addition, reports were
      solicited from the Canadian proprietary manufacturers of SSRIs, and from the
      Therapeutic Products Program of Health Canada. Each case was then classified
      according to the description of the movement disorder, based on predefined
      diagnostic criteria. RESULTS: A total of 127 published reports of SSRI-induced
      movement disorders were identified involving akathisia (n = 30), dystonia (19),
      dyskinesia (12), tardive dyskinesia (6), parkinsonism (25), and 15 cases of mixed
      disorders. Ten isolated cases of bruxism were identified. Ten additional reports
      could not be classified. Manufacturers of SSRIs provided 49 reports of akathisia,
      44 of dystonia, 208 of dyskinesia, 76 of tardive dyskinesia, 516 of parkinsonism,
      and 60 of bruxism. Treatment strategies included discontinuation of the SSRI;
      dosage reduction; or the addition of a benzodiazepine, beta-blocker, or
      anticholinergic agent. CONCLUSIONS: SSRI use appears to be associated with the
      development of movement disorders, as either a direct result of the drug or
      exacerbation of an underlying condition. Predisposing factors may include the use
      of neuroleptics, existing neurologic diagnoses, or preexisting movement
      disorders. Clinicians should be cognizant of the potential for these reactions,
      as prompt recognition and management is essential in preventing potentially
      significant patient morbidity.

PMID- 9640490
TI  - Beta-blockers and depression: the more the murkier?
AB  - OBJECTIVE: To review the literature regarding the purported association between
      oral ingestion of beta-blocker drugs and depressed mood. DATA SOURCE: MEDLINE was
      searched for published articles using the key words propranolol, atenolol,
      metoprolol, nadolol, timolol, beta-blocker, beta-adrenergic antagonist, or beta
      adrenergic blocker in combination with the key words depression, depressive
      symptomatology, major depressive disorder, or depressed mood from January 1966
      through December 1996. DATA SYNTHESIS: Findings regarding the association are
      equivocal. Plausible explanations include study design, case definition, and
      confounding disease states. Most of the evidence supporting an association has
      used case series and case reports. Findings from cross-sectional observational
      studies and case-control studies are equivocal. Case definition and measurement
      instruments may partially explain these inconsistencies. Studies using a
      diagnosis of depression generally do not support the relationship. Trials using
      depressive symptoms are about evenly split, but they have generally enrolled a
      small number of patients and have questionable statistical power. Studies
      defining antidepressant prescriptions dispensed as a marker for depression
      generally support the association. Evidence exists both for and against the
      hypothesis that lipophilic beta-blockers cause more depression than do
      hydrophilic beta-blockers. CONCLUSIONS: beta-Blockers may have been unjustly
      associated with depression and their use avoided for that reason. Future studies
      into the association between depression and beta-blocker use should evaluate
      whether the association is affected by case definition and study design
      characteristics, including disease, dose-response, bias, measurement error, or
      ability to precisely measure the length of the exposure.

PMID- 9640491
TI  - Oral ketoconazole in cutaneous fungal infections.
AB  - Few data are available on the mechanism by which oral ketoconazole reaches the
      stratum corneum and exhibits its antifungal activity. The rapid onset of effect
      and the isolation of ketoconazole from the sweat support the theory that this
      agent reaches its site of action through eccrine sweat secretion. However,
      passive diffusion from the bloodstream and sebum secretion may also account for
      the antimycotic effect at the level of the stratum corneum. Oral ketoconazole has
      been shown to be effective in a variety of cutaneous fungal infections. However,
      systemic antifungal therapy is best reserved for extensive infections or those
      resistant to topical therapy.

PMID- 9640492
TI  - Movement disturbances associated with the use of selective serotonin-reuptake
      inhibitors.

PMID- 9640493
TI  - Comment: modification of weight-based heparin nomogram.

PMID- 9640494
TI  - Comment: cost-effective pharmaceutical care for HIV disease.

PMID- 9640495
TI  - Expression of the autoreactive Ig repertoire in a large family, with high
      prevalence of thyroid autoimmune diseases.
AB  - We have investigated the autoreactive Ig repertoire expressed by sera Ig of
      patients and healthy relatives individuals, who belong to a large family with
      high prevalence of autoimmune thyroid diseases (AITD). We have used a panel of
      thyroid, muscular and nuclear self antigens. IgG autoantibodies directed against
      thyroid antigens were found in 17 out of 29 patients (58.62%) and in 10 out of 46
      (21.7%) of relatives sera which suggested that some relatives were either
      predisposed to develop the AITD or already affected with AITD. IgM natural
      autoantibodies (NAAb) directed against muscular and nuclear antigens were found
      in 27 out of 46 (58.69%) of healthy individuals but not exhibited in all of the
      patients. In relative's sera, the presence of anti-Tg and anti-TPO seems to be
      associated with the increase of the NAAb activity. Our Data suggested that The
      emergence of anti-Tg and anti-TPO auto-antibodies is secondary to a polyclonal
      activation.

PMID- 9640496
TI  - [Myxomatosis in Tunisia: seroepidemiological study in the Monastir region
      (Tunisia)].
AB  - A sero-epidemiological study of myxomatosis, realized in the region of Monastir,
      confirmed the existence and the prevalence of the disease in its nodular form.
      Different strains of the myxomatosis virus were isolated and identified by gel
      immunodiffusion test (GID) using specific polyclonal sera. Serological analyses
      using complement fixation (FC) and (GID) tests allowed the detection of specific
      antibodies in sera from both healthy and sick animals. The results also confirmed
      the better sensitivity of the FC over the GID. Overall rates infection of herds
      and animals were 54.9% and 32.63% (p < 0.05), respectively, as revealed by
      serological testing. These rates increase with the size of herds. Geographic
      distribution of myxomatosis cases suggests that the disease first appeared in the
      coastal region then moved inside the Sabel area. Breeding and farming conditions,
      associated with deficiency in sanitary and medical measures, are at the origin of
      the introduction and the wide distribution of myxomatosis in this region.

PMID- 9640497
TI  - [Isolation of salmonella in wastewaters and study of indicator bacteria survival
      in soils].
AB  - Detection of salmonella in wastewaters was done in semi-industrial pilot plant.
      In parallel, survival of indicator bacteria (feacal coliforms and feacal
      streptococci) in the soil was evaluated into a laboratory incubation device.
      Results revealed the isolation of 21 strains of salmonella in 7 campaigns of
      analysis on DCLS media, and 6 strains on lactose-green-brilliant and phenol red
      media in 2 campaigns. Salmonella were recovered in all the lines of wastewater
      treatment. The study led on the survival of coliforms and streptococci bacteria
      allowed the conclusion that feacal streptococci introduced by wastewaters were
      more qualified to survive in the soil than feacal coliforms. On the other hand,
      feacal coliforms appeared more sensitive to the biological factors of the soil
      than feacal streptococci. The ambient temperature of incubation situated between
      12 and 24 degrees C seemed suitable for bacteria survival in the soils.

PMID- 9640498
TI  - [Epidemiological and clinical profile of superficial mycoses in the Monastir
      region (Tunisia). Retrospective study (1991-1994) of 3578 cases].
AB  - Despite of socio-economical improvement in our population and the efficacy of
      available antifungal treatment, superficial mycoses remain a common condition in
      dermatologic practice. To determine the epidemio-clinical pattern of superficial
      mycoses in our region, a retrospective study of 3578 cases have been carried out
      in the Department of Dermatology of the University Hospital of Monastir during a
      4 year-period. The mean age of patients was 33 years (range: 6 months-91 years).
      The male to female sex-ratio was 0.82. Rural origin, history of previous mycoses,
      diabetes, topic or systemic corticosteroids and the presence of animals in
      surroundings were the most predisposing factors. The most frequent clinical
      patterns were: tinea corcoris and pedis (40.3%), Tinea versicolor (21.6%), Tinea
      capitis (9.7%) dermatophytosis of hairless skin (9.6%) and onychomycosis (8.6%).
      Dermatophyte was the most frequent (55.5%). The occurrence of superficial mycose
      especially if it affects diffuse area of the body, or if it is relapsing and
      resistant to treatment, requires looking for predisposing factors.

PMID- 9640499
TI  - [Study of symbiotic, serological and antibiotic resistance characteristics of
      different Rhizobium cicerii strains].
AB  - The symbiotic performance of 24 isolates of Rhizobium Cicerii, collected from
      different Tunisien soils, were studied in a growth room and compared to the
      performance of two international strains (Som and 43). The antibiotic and
      serologic tests showed a large biogenetic diversity among the different isolates.
      Three serogroups gathering 18 isolates have been identified. Monchar strain
      (isolat 12) was shown to be resistant to all the six different antibiotic used.
      The standard strain 43 produced the greatest number of nodules and the best
      nitrogen yield in association with "Amdoun" roots, whereas the Menzel bouzelfa
      isolate brought about the best nitrogen yield in association with "Amdoun" and
      thus was the most efficient. An interesting result, consisted on the existence of
      a significant correlation (r = 0.67) between streptomycin resistance of the
      isolates and their capacity of nodule initiation (infectivity).

PMID- 9640500
TI  - [Pollen density calender in Tunisia].
AB  - The pollen calendar of the region on Tunis atmosphere was established and the
      weekly variations of the pollen density of the 25 main taxones were studied. This
      calendar showed an identity reflecting the surrounding vegetation modulated by
      the pollen production of neighbouring regions and other far-off areas. This
      should allow the allergist to predict the critical periods for the patients and
      to advice him the specific treatment. On the other hand, it would demonstrate the
      usefulness, in using a series of skin tests, certain European pollens which are
      partially or totally absent in the atmosphere of Tunis. However, it would be
      desirable controlling the allergic capacity of pollens which are not tested up to
      now and could be found in non negligible concentrations in the atmosphere.

PMID- 9640501
TI  - [Estimation of fertility and quality of oocytes emitted by the clam Ruditapes
      decussatus (Linnaeus 1758) during experimental inductions].
AB  - Experimental inductions were carried out on some genitors of clams Ruditapes
      decussatus to obtain sexual emissions and estimate the fecondity of this species.
      The genitors were collected from two sites of tunisian littoral. Higher percent
      of oocytes was found in summer with a maximum of 52 x 10(4) oocytes in Gargour
      (Golf of Gabes) against 45 x 10(4) in Menzel-Jemil (Lagoon of Bizerte). The
      observation under the electronic microscope of free oocytes allowed us to
      subdivised them in three groupes: immatures, matures and atretics. Only mature
      oocytes were susceptible to be feconded and underwent larval development with
      unknown proportion.

PMID- 9640502
TI  - [Cerbussowia cerruti Wilhelmi 1901, from the Tunisian Golf (Platyhelminths,
      marine Tricladida)].
AB  - Cerbussowia cerruti Wilhelmi, 1909 (Plathyhelminthe, Turbellaria, Tricladida) is
      described in Tunisia for the first time. A morphological, anatomical and
      histological accounts of this marine flatworm are presented. Some differences
      between the anterior ends of the tunisian animals and accounts in the literature
      are discussed.

PMID- 9640503
TI  - [Trace metals: zinc and copper in Tunisian littoral fishes].
AB  - Investigations have been carried out in order to find out whether zinc and copper
      are or not accumulated in flesh and organs of some edible fish of a polluted
      area, namely Sfax. Tracking zinc and copper was our first aim, the second was the
      determination of an organotropism of the two metals. Finally, our results, would
      help stating whether or not Sfax-shore is polluted with zinc and copper.

PMID- 9640504
TI  - [Minerals in Tunisia's drinking water].
AB  - We have made the physico-chemical analysis of drinking waters sampled from
      different Tunisian areas. The results obtained show that those waters are rich in
      mineral elements particularly those of the south of the country. Calcium and
      magnesium level in south drinking water is about three times higher than the
      maximum admitted concentration by WHO an EEC. The sodium, chloride and sulfate
      level is twice higher. The nitrate contents slightly exceeds the EEC guide level.
      The high mineralization observed needs a chemical quality improvement of those
      waters.

PMID- 9640505
TI  - Hormone replacement.

PMID- 9640506
TI  - Patients as partners. Encouraging lifestyle changes through feedback.

PMID- 9640507
TI  - Close friends as patients in rural practice.

PMID- 9640508
TI  - Medical services supply measurement. A case for access modeling.

PMID- 9640509
TI  - No remuneration for telephone renewals.

PMID- 9640510
TI  - Rejecting the facts.

PMID- 9640511
TI  - Keeping an open mind.

PMID- 9640512
TI  - What we need to know.

PMID- 9640513
TI  - Preparing LET solution.

PMID- 9640514
TI  - Comparing antihypertensive agents.

PMID- 9640515
TI  - Therapeutic approach to hypertension during pregnancy.
AB  - QuestionQuite a few of my pregnant patients have hypertensive disorders. What is
      the threshold for treating hypertension during pregnancy? Which of the various
      antihypertensive agents are considered safe during pregnancy?AnswerPharmacologic
      therapy could benefit mother and baby when diastolic pressure exceeds 110 mm Hg.
      Preeclampsia must be followed closely. Methyldopa (eg, Aldomet) and hydralazine
      (eg, Apresoline) are still the drugs of choice during pregnancy, although the
      safety and efficacy of calcium channel blockers and Beta-blockers appear well
      established.

PMID- 9640516
TI  - Ophthaproblem. Chalazion.

PMID- 9640517
TI  - Dermacase. Tuberous sclerosis (Bourneville's disease).

PMID- 9640518
TI  - Emergency treatment of paraphimosis.

PMID- 9640519
TI  - Should we be giving all children with otitis media antibiotics?

PMID- 9640520
TI  - Peak flow meters for asthma patients. Do they up the benefits or up the costs?

PMID- 9640521
TI  - Alternative treatments for menopausal symptoms. Qualitative study of women's
      experiences.
AB  - OBJECTIVE: To describe women's experiences with alternative treatments for
      symptoms attributed to menopause. DESIGN: Descriptive qualitative study. SETTING:
      Personal interviews and focus groups were conducted in private rooms at the
      Toronto Hospital; telephone interviews were conducted at mutually convenient
      times. PARTICIPANTS: Thirteen perimenopausal women with a mean age of 52.6 +/-
      2.6 years who were experiencing symptoms attributed to menopause and were using
      alternative therapies participated in the study. METHOD: Women using alternative
      therapies for menopausal symptoms were recruited via posted notices and were
      screened over the telephone. Data were collected during semistructured personal
      interviews, telephone interviews, and a focus group. All interviews were
      audiotaped, transcribed, and mailed to participants for verification. Recruitment
      continued until theme saturation was reached. MAIN FINDINGS: Because of their
      "natural" origin, the women perceived alternative treatments to be safe and
      considered them somewhat effective. Factors influencing use of alternative
      therapies included personal control over health, confidence in advice from
      nonphysicians, perceived pressure from physicians to use hormone replacement
      therapy, and physicians' disinterest and frequently negative attitudes toward
      alternatives. CONCLUSION: Personal control was a central issue. Helping women
      during their menopausal years feel they have some control over their health,
      including their informed choice of treatments, might help them to trust their
      physicians more and to feel more confident in their ultimate treatment decisions,
      which might include improvements in health behaviour.

PMID- 9640522
TI  - [Factors influencing the adoption of hormone replacement therapy].
AB  - OBJECTIVE: To develop and test the metrologic qualities of a questionnaire for a
      survey on determining factors in initiating hormone replacement therapy (HRT),
      using Ajzen's planned behaviour theory. DESIGN: Semistructured interviews to
      collect the behavioural beliefs needed to develop the questionnaire and the test
      retest. SETTING: Family medicine practices and the community. PARTICIPANTS: In
      two family medicine practices, 42 women completed semistructured interviews that
      yielded the beliefs needed to design the questionnaire for the core survey.
      Thirty other women from the community took part in the test-retest 2 weeks later.
      MAIN OUTCOME MEASURES: The internal consistency of the constructs (tendency of
      answers within a group of questions) was determined using Cronbach's alpha
      coefficient. Stability of the global constructs (proportion of subjects who had
      an absolute difference in their scores of less than 1 between the two
      measurements) was determined using the adjusted agreement coefficient (adjusted
      Po). RESULTS: Findings for 12 of the 14 global constructs were above the
      acceptance threshold of 0.60. In one case alpha could not be measured because
      there was only one question for measuring it. On the test-retest, 12 of the 14
      adjusted Pos had a reliability rating at or above 80%. CONCLUSION: The
      questionnaire developed using Ajzen's planned behaviour theory had the requisite
      metrologic qualities for integration into the core survey on determining factors
      for initiating HRT.

PMID- 9640523
TI  - Hypercholesterolemia screening. Does knowledge of blood cholesterol level affect
      dietary fat intake?
AB  - OBJECTIVE: To assess whether knowing blood cholesterol test results influences
      people's intention to lower their dietary fat intake and to assess changes in
      diet after 3 months. DESIGN: Randomized clinical study. SETTING: Two hospital
      based family medicine centres. PARTICIPANTS: A total of 526 patients aged 18 to
      65, without prior knowledge of their blood cholesterol levels, were recruited.
      Seventy did not appear for their appointments, and 37 did not meet study
      criteria, leaving 419 participants. From that group, 391 completed the study.
      INTERVENTIONS: Patients submitted to cholesterol screening were randomly assigned
      to one of two groups, completing the study questionnaires either before (control
      group) or after (experimental group) being informed of their screening test
      results. All participants were called 3 months after transmission of test results
      to assess their dietary fat intake at that time. MAIN OUTCOME MEASURES:
      Differences in intention to adopt a low-fat diet reported between the
      experimental and control groups and differences in dietary fat intake
      modification after 3 months between patients with normal and abnormal blood
      cholesterol test results. RESULTS: Knowledge of test results influenced patients'
      intentions to adopt low-fat diets (F1,417 = 5.4, P = .02). Patients reported
      lower mean dietary fat intake after 3 months than at baseline (P < .0001). The
      reduction was greater in patients with abnormal screening results (F2,388 = 3.6,
      P = .03). CONCLUSIONS: Being informed of personal blood cholesterol levels
      effects an immediate change in eating habits that translates into reduced dietary
      fat intake.

PMID- 9640525
TI  - Initial experience of McMaster SmokeStop. Smoking Cessation Clinic at McMaster
      Family Practice Unit.
AB  - PROBLEM ADDRESSED: There are very few smoking cessation resources in the
      community, and many family physicians have not incorporated smoking cessation
      counseling into their practices. Yet many smokers are interested in individual
      assistance to stop smoking. McMaster SmokeStop is a unique smoking cessation
      program that operates within the Family Practice Unit at McMaster University
      Medical Centre. The program has been in operation since October 1994. Additional
      clinics have been established at three other Hamilton hospitals and a community
      health centre in the past year. OBJECTIVE OF PROGRAM: To assist people to change
      smoking behaviour by quitting, cutting down, or making progress toward quitting
      as manifested by an advance in stage of change using the Prochaska and DiClemente
      model. The program was established in response to requests from various health
      care providers who wanted to refer difficult and challenging smoking patients.
      MAIN COMPONENTS OF PROGRAM: Using an individual counseling approach, the program
      assists smokers with the use of reflective listening and support as well as, when
      indicated, acupuncture, nicotine patch, nicotine gum, stress management, and
      behaviour modification. Thirty to 60 minutes are allowed for initial appointments
      and 15 to 30 minutes for follow-up appointments. CONCLUSION: The program has
      become a popular resource for health care providers in the community who refer
      difficult smoking patients. Because of increasing numbers of smokers who wish to
      attend, the clinics have expanded considerably.

PMID- 9640524
TI  - Alternative treatments for menopausal symptoms. Systematic review of scientific
      and lay literature.
AB  - OBJECTIVE: To review the scientific literature on common alternative remedies for
      treatment of symptoms attributed to menopause and to contrast this with available
      lay literature. QUALITY OF EVIDENCE: Scientific articles were identified by
      searching MEDLINE, CINAHL, and HEALTH databases from 1966 to mid-1997 for English
      language articles. More than 200 references were reviewed; 85 were selected for
      citation based on specific reference to alternative medicine for symptoms
      commonly attributed to menopause (e.g., hot flashes), to the effects of changing
      estrogen levels (e.g., irregular menses, vaginal dryness), and to reported side
      effects of the treatments. MAIN FINDINGS: The scientific literature was
      categorized under the headings nutritional supplements, herbal remedies,
      homeopathic remedies, and physical approaches. Some scientific evidence of the
      safety and efficacy of alternative treatments during menopause was uncovered,
      with the strongest evidence emerging in favour of phytoestrogens, which occur in
      high concentrations as isoflavones in soy products. CONCLUSIONS: In available
      controlled studies, the strongest data support phytoestrogens for their role in
      diminishing menopausal symptoms related to estrogen deficiency and for possible
      protective effects on bones and the cardiovascular system. Randomized controlled
      trials, standardization of dosage, and accurate safety and efficacy labeling are
      required to ensure proper use of alternative remedies.

PMID- 9640526
TI  - Eradicating tuberculosis. Report on the National Consensus Conference on
      Tuberculosis.

PMID- 9640527
TI  - BC whiplash initiative.

PMID- 9640528
TI  - Nucleus and gene expression.

PMID- 9640529
TI  - New systems for replicating DNA in vitro.
AB  - Current paradigms for the regulation of genomic DNA replication in eukaryotes are
      derived primarily from cell fusion experiments, yeast genetics, and from in vitro
      assays in Xenopus egg extracts. Initially, many aspects seemed irreconcilably
      different among the various organisms and model systems. In the past year,
      however, divergent approaches have arrived at a consensus on how the cell cycle
      regulates the initiation of DNA replication. All major players appear to be
      conserved from yeast to vertebrates, yet the important challenge of
      reconstituting eukaryotic replication from purified components remains. Three
      novel in vitro assays that replicate nuclear templates bring us closer to this
      goal.

PMID- 9640530
TI  - DNA mismatch repair and cancer.
AB  - Mutations in DNA mismatch repair (MMR) genes have been associated with hereditary
      nonpolyposis colorectal cancer. Studies in bacteria, yeast and mammals suggest
      that the basic components of the MMR system are evolutionarily conserved, but
      studies in eukaryotes also imply novel functions for MMR proteins. Recent results
      suggest that mutations in MMR genes lead to tumorigenesis in mice, but DNA
      replication errors appear to be insufficient to initiate intestinal tumorigenesis
      in this model system. Additionally, MMR-deficient cell lines display a mutator
      phenotype and resistance to several cytotoxic agents, including compounds widely
      used in cancer chemotherapy.

PMID- 9640531
TI  - SMC protein complexes and higher-order chromosome dynamics.
AB  - The structural maintenance of chromosome (SMC) family of proteins represents an
      expanding group of chromosomal ATPases that are highly conserved among Bacteria,
      Archaea and Eukarya. During the past year, significant progress has been made
      towards understanding the cellular functions and molecular activities of this new
      class of proteins. Emerging evidence suggests that eukaryotic SMC proteins form
      large protein complexes with non-SMC subunits and act as key components for a
      wide variety of higher-order chromosome dynamics.

PMID- 9640532
TI  - The cellular organization of gene expression.
AB  - Recent cell biological observations have provided new insights into how
      transcription, pre-mRNA splicing and 3' processing are organized and coordinated
      with each other in the mammalian cell nucleus. Morphological observations are
      supported by biochemical evidence that suggests physical interactions between
      components of the transcription and RNA processing machineries. A working model
      of the cellular organization of gene expression is now emerging.

PMID- 9640533
TI  - Telomeres, the nucleolus and aging.
AB  - Reactivation of telomerase in cultured human cells extends their replicative life
      span beyond the Hayflick limit. How telomere shortening triggers cell senescence
      and whether it contributes to aging in vivo are under investigation. Studies in
      yeast have revealed another site critical to cellular aging: the nucleolus. The
      accumulation of ribosomal DNA circles is a cause of aging in this organism. The
      possible relevance of this mechanism to human aging is also being considered.

PMID- 9640534
TI  - Life with nucleosomes: chromatin remodelling in gene regulation.
AB  - In the past year, the role of chromatin has emerged at the forefront of
      transcription research. Discovery and characterisation of the chromatin modifying
      machinery have significantly advanced our understanding of the molecular
      activities that establish a transcriptionally competent substrate in vivo, and
      have underscored the importance of the part played by chromatin in the regulation
      of transcription.

PMID- 9640535
TI  - Chromatin-remodeling factors: machines that regulate?
AB  - Chromatin has shifted into the focus of attention as a key to understanding the
      regulation of nuclear processes such as transcription. Protein machines have been
      described that use the energy of ATP to render chromatin dynamic and hence
      active, but which may also be involved in chromatin assembly. The discovery of
      three different Drosophila nucleosome remodeling complexes that contain imitation
      switch (ISWI), an ATPase with a high degree of sequence conservation from yeast
      to human, points to a central function of this ATPase in chromatin dynamics.

PMID- 9640536
TI  - Chromo-domain proteins: linking chromatin structure to epigenetic regulation.
AB  - Chromo-domain proteins appear to be a central component in the epigenetic
      regulation of heterochromatin function and euchromatic gene expression. The
      recent discovery of a variety of interacting partners of chromo-domain proteins
      is yielding new molecular insights into epigenetic regulatory processes acting at
      the level of higher order chromatin structure.

PMID- 9640537
TI  - Locus control regions, chromatin activation and transcription.
AB  - The past year has seen interesting advances in our understanding of the action of
      locus control regions. For the first time, the chromosomal distance was described
      in detail as a parameter in positive/negative regulation of transcription via
      gene competition. A number of publications have also described negative
      regulatory elements which restrict the action of locus control regions and other
      regulatory regions to specific genes and/or specific tissues. The emerging
      picture indicates that several very different types of negative regulation ensure
      that transcriptional activation occurs only in the appropriate cells.

PMID- 9640538
TI  - TCF: transcriptional activator or repressor?
AB  - T cell factor, or TCF, has been identified as the transcriptional response factor
      activated by Wnt-1 and Wingless signalling. TCF is thought to be a potent
      architectural factor which facilitates assembly of multiprotein enhancer
      complexes. Its deregulation in the colonic epithelium, and in other cells, leads
      to cancer. This raises the question of how TCF is kept inactive in unstimulated
      cells.

PMID- 9640539
TI  - Co-activators and co-repressors in the integration of transcriptional responses.
AB  - The nuclear hormone receptors are DNA binding transcription factors that are
      regulated by binding of ligands, switching them from an inactive or repressive
      state to gene-activating functions. Recent evidence supports the hypothesis that
      many nuclear receptors switch, in a ligand-dependent manner, between binding of a
      multicomponent co-repressor complex containing histone deacetyltransferase
      activity, and binding of a co-activator complex containing factors with histone
      acetyltransferase activity that are further regulated by diverse signal
      transduction pathways. The identification of these limiting co-repressor and co
      activator complexes and their specific interaction motifs, in concert with
      solution of the structures of the receptor ligand-binding domain in apo (empty)
      and ligand bound forms, indicates a common molecular mechanism by which these
      factors activate and repress gene transcription.

PMID- 9640540
TI  - The nuclear receptor ligand-binding domain: structure and function.
AB  - In the past few years our understanding of nuclear receptor action has
      dramatically improved as a result of the elucidation of the crystal structures of
      the empty (apo) ligand-binding domains of the nuclear receptor and of complexes
      formed by the nuclear receptor's ligand-binding domain bound to agonists and
      antagonists. Furthermore, the concomitant identification and functional analysis
      of co-regulators (transcriptional intermediary factors [TIFs], comprising co
      activators and co-repressors) previously predicted from squelching studies, have
      deepened this understanding. Recent data have provided the structural basis for
      the specific recognition of ligands and the molecular mechanisms of agonism and
      antagonism, enabling us to gain a comprehensive view of the early steps of
      nuclear receptor action.

PMID- 9640541
TI  - Transport routes through the nuclear pore complex.
AB  - The nuclear pore complex can be considered to be the stationary phase of
      bidirectional traffic between the nucleus and the cytoplasm. The mobile phase
      consists of karyopherins, transport substrates, and the small GTPase Ran and its
      modulators. Recently, the family of karyopherins was expanded with the
      recognition of numerous open reading frames with limited homology to karyopherin
      beta 1. In several cases, the specific substrates transported by the new
      karyopherins have been identified, allowing the characterization of new pathways
      into and out of the nucleus. However, the mechanisms of transport, particularly
      the role of Ran, remain poorly understood.

PMID- 9640542
TI  - Functions of the GTPase Ran in RNA export from the nucleus.
AB  - Significant and exciting advances in the field of RNA and protein export have
      been made recently, due in large part to discovery of the roles played by Ran, a
      small, soluble GTPase present in both the nucleus and cytoplasm of all eukaryotic
      cells. Ran is thought to be primarily bound to GTP in the nucleus and to GDP in
      the cytoplasm, as a result of the assymetric distribution of factors that
      interact with Ran to promote guanine nucleotide exchange (in the nucleus) and GTP
      hydrolysis (in the cytoplasm). A key function of the nuclear Ran.GTP is to
      support formation of complexes containing an export receptor (an exportin) and
      cargos such as RNAs, RNPs or proteins that are destined for export. In the
      cytoplasm, removal of the Ran.GTP from the complex results in its destabilization
      and release of the export cargo. Although Ran.GTP is required for formation of
      the export complex, GTP hydrolysis does not appear to be necessary for
      translocation through the nuclear pore complex or cytoplasmic release.
      Nevertheless, the GTPase of Ran does appear to be required in as yet unidentified
      intranuclear steps prior to export of some, but not all, RNAs.

PMID- 9640543
TI  - Nuclear envelope and nuclear pore assembly: analysis of assembly intermediates by
      electron microscopy.
AB  - At mitosis, the nucleus of higher eukaryotic cells disassemblies into components
      which subsequently reform functional nuclear envelopes in the two daughter cells.
      The molecular mechanisms underlying this remarkable morphological reorganization
      are the focus of active investigation. Recent electron microscopy techniques have
      provided intriguing glimpses of intermediate structures in both nuclear envelope
      and nuclear pore complex reassembly.

PMID- 9640544
TI  - Peripheral vascular disease, Part 2.

PMID- 9640545
TI  - Money-irritation.

PMID- 9640546
TI  - The safety of bleaching creams containing hydroquinone.

PMID- 9640547
TI  - Hereditary papulotranslucent acrokeratoderma.

PMID- 9640548
TI  - A dermatologic diary. Portrait of a new life.

PMID- 9640549
TI  - Surgical management of rhinophyma.

PMID- 9640550
TI  - Aquatic adversaries: shark bites.

PMID- 9640551
TI  - Do you anticipate that you will be seeing a greater or lesser amount of patients
      with melanoma due to the media blitz concerning sun awareness and skin
      protection?

PMID- 9640553
TI  - Rosaceous lymphedema: a rare variant of a common disorder.
AB  - Rosaceous lymphedema is considered to be a rare and disfiguring variant of acne
      rosacea. Cases remain difficult to treat and can challenge afflicted patients
      both cosmetically and psychologically. We describe an unusual presentation of
      rosaceous lymphedema and review the differential diagnosis of persistent facial
      edema.

PMID- 9640554
TI  - POEMS syndrome in a patient with diabetic ketoacidosis: case report and review.
AB  - POEMS syndrome is an uncommon multisystem disorder characterized by the
      combination of polyneuropathy, organomegaly, endocrinopathy, monoclonal
      gammopathy, and skin changes. A 57-year-old man diagnosed with POEMS syndrome
      after presenting with diabetic ketoacidosis and characteristic skin lesions is
      reported. The dermatologic and systemic manifestations of this unusual syndrome
      are reviewed.

PMID- 9640555
TI  - Perceived deprivation of social touch in psoriasis is associated with greater
      psychologic morbidity: an index of the stigma experience in dermatologic
      disorders.
AB  - Touch is a powerful medium of social validation. Patients with skin disorders
      often experience social rejection when people avoid touching them, possibly
      fearing contagion or filth. We examined the psychologic impact of the stigma
      experience among 137 patients with moderate to severe psoriasis; 26.3 percent of
      patients reported that during the previous month they had experienced an episode
      when "people made a conscious effort not to touch them" because of their
      psoriasis. The stigmatized group did not have greater psoriasis severity than the
      non-stigmatized control group. However, in contrast to the non-stigmatized group,
      the stigmatized group had higher (P = 0.0003) depression scores (in the range for
      clinical depression, as measured by the Carroll Rating Scale for Depression), by
      stepwise logistic regression analysis using a wide range of psychopathologic
      measures as the independent variables. These findings underline the profound
      impact of the stigma experience in psoriasis, and possibly other dermatologic
      conditions that are associated with social stigma.

PMID- 9640556
TI  - Effective sunscreen ingredients and cutaneous irritation in patients with
      rosacea.
AB  - Patients with rosacea are particularly susceptible to the irritation caused by
      sunscreen ingredients. The purpose of this bilateral comparison study was to
      examine the effects of different ingredients found in sunscreen on facial
      cutaneous irritancy in patients with rosacea. patients clinically diagnosed with
      rosacea were asked to test different preparations of common sunscreens on their
      faces. The results show that the presence or absence of appropriate protective
      ingredients, such as dimethicone and cyclomethicone in the vehicle, may prevent
      irritation from other sunscreen ingredients in patients with inflammatory
      conditions such as rosacea.

PMID- 9640557
TI  - An evaluation of the effect of an alpha hydroxy acid-blend skin cream in the
      cosmetic improvement of symptoms of moderate to severe xerosis, epidermolytic
      hyperkeratosis, and ichthyosis.
AB  - A number of genetic, intrinsic, and extrinsic factors can cause conditions of
      problem dry skin, marked by unusual dryness, rough texture, and extreme flaking
      and scaling, that are generally not controlled by conventional moisturizers. A
      study was undertaken to evaluate the safety and efficacy of two novel alpha
      hydroxy acid (AHA)-containing creams in reducing the appearance and symptoms of
      problem dry skin on subjects with a range of dry skin conditions, including
      xerosis, epidermolytic hyperkeratosis, and ichthyosis. Twenty subjects completed
      a course of treatment with either regular or extra strength AHA-blend cream on a
      test site, compared with a currently marketed, non-AHA moisturizing lotion on a
      control site. Subjects were treated for 4 weeks, with clinical evaluations
      performed at weeks 0, 2, and 4. The test for mulations reduced symptoms and
      improved cosmetic appearance following 2 weeks of use, with continued improvement
      following 4 weeks of use. Improvements were significant compared to baseline and
      compared to sites treated with the control lotion. Some patients experienced mild
      to moderate local adverse effects; all subjects were able to continue using the
      test product for the duration of the study.

PMID- 9640558
TI  - The causes and treatment of pseudofolliculitis barbae.
AB  - Pseudofolliculitis barbae, commonly referred to as "razor bumps" or "ingrown
      hairs," is a papular and pustular, foreign body inflammatory reaction that can
      affect any individual who has curly hair and who shaves. This condition is a
      particular nuisance to African-Americans. This report will discuss the causes of
      pseudofolliculitis barbae and present a systematic approach to treatment.

PMID- 9640559
TI  - Chaos game representation of proteins.
AB  - The present report proposes a new method for the chaos game representation (CGR)
      of different families of proteins. Using concatenated amino acid sequences of
      proteins belonging to a particular family and a 12-sided regular polygon, each
      vertex of which represents a group of amino acid residues leading to conservative
      substitutions, the method can generate the CGR of the family and allows pictorial
      representation of the pattern characterizing the family. An estimation of the
      percentages of points plotted in different segments of the CGR (grid points)
      allows quantification of the nonrandomness of the CGR patterns generated. The
      CGRs of different protein families exhibited distinct visually identifiable
      patterns. This implies that different functional classes of proteins follow
      specific statistical biases in the distribution of different mono-, di-, tri-, or
      higher order peptides along their primary sequences. The potential of grid counts
      as the discriminative and diagnostic signature of a family of proteins is
      discussed.

PMID- 9640560
TI  - Comparative molecular modeling study of the three-dimensional structures of
      prostaglandin endoperoxide H2 synthase 1 and 2 (COX-1 and COX-2).
AB  - To understand the structural features that dictate the selectivity of diverse
      nonsteroidal antiinflammatory drugs for the two isoforms of the human
      prostaglandin H2 synthase (PGHS), the three-dimensional (3D) structure of human
      COX-2 was assessed by means of sequence homology modeling. The ovine COX-1
      structure, solved by X-ray diffraction methods and sharing a 61% sequence
      identity with human COX-2, was used as template. Both structures were energy
      minimized using the AMBER 4.0 force field with a dielectric constant of 4r. (S)
      Flurbiprofen, a nonselective COX inhibitor, and SC-558, a COX-2-selective ligand,
      were docked at the cyclooxygenase binding site in both isozymes, evidencing the
      role of different residues in the ligand-protein interaction. The 3D structures
      of the constructed four ligand-enzyme complexes were refined by energy
      minimization. Molecular dynamics simulations were also carried out, to understand
      more deeply the structural origins of the selectivity. Distances calculated
      during the dynamics process between the different ligands and the interacting
      residues of the two PGHS isozymes provided evidence of the flexible nature of the
      cyclooxygenase active site, permitting the identification of different conserved
      and nonconserved residues as responsible for ligand selectivity.

PMID- 9640561
TI  - Visualization of solvation structures in liquid mixtures.
AB  - Spatial distribution functions of atomic densities. SDFs, have been proposed as a
      natural starting point for analysis of local molecular structure in liquids and
      solutions. The local structure in these systems is often complex and this is
      reflected in the fact that SDFs can be difficult to visualize. Among the
      different methods that can be used to visualize SDFs we discuss 3D isodensity
      surfaces, cross-sections, and 'comic book' animations. We also discuss the
      possibility of a simultaneous visualization of SDFs and other 3D fields, such as
      the electron density. These techniques are all intended to emphasize and bring
      out aspects of SDFs that promote a further understanding of the local molecular
      structure. OpenGL-based software has been used under X-Windows to implement these
      techniques, and we argue that high-quality molecular graphics need not be
      expensive. Data from a molecular dynamics simulation of an equimolar binary
      mixture of water and acetonitrile have been used to illustrate the discussion.

PMID- 9640562
TI  - Modeling of the three-dimensional structure of the human melanocortin 1 receptor,
      using an automated method and docking of a rigid cyclic melanocyte-stimulating
      hormone core peptide.
AB  - A model is presented of the melanocortin 1 receptor (MC1R), constructed by use of
      an unbiased, objective method. The model is created directly from data derived
      from multiple sequence analysis, a low-resolution EM-projection map of rhodopsin,
      and the approximate membrane thickness. The model agrees well with available data
      concerning natural mutations of MC1Rs occurring in different species. A model is
      also presented of the most rigid ligand for this receptor, the cyclic
      pentapeptide cHFRWG, shown docked in the receptor model. The receptor-ligand
      complex model agrees well with available experimental data. The ligand is located
      between transmembrane region 1 (TM1), TM2, TM3, TM6, and TM7 of the receptor.
      Multiple interactions occur between ligand and receptor, including interactions
      with Leu-48 (TM1), Ser-52 (TM1), Glu-55 (TM1), Asn-91 (TM2), Glu-94 (TM2), Thr-95
      (TM2) Ile-98 (TM2), Asp-121 (TM3), Thr-124 (TM3), Phe-257 (TM6), Phe-283 (TM7),
      Asn-290 (TM7), and Asp-294 (TM7) of the receptor.

PMID- 9640563
TI  - External and internal electrostatic potentials of cholinesterase models.
AB  - The electrostatic potentials for the three-dimensional structures of
      cholinesterases from various species were calculated, using the Delphi algorithm,
      on the basis of the Poisson-Boltzmann equation. We used structures for Torpedo
      californica and mouse acetylcholinesterase, and built homology models of the
      human, Bungarus fasciatus, and Drosophila melanogaster acetylcholinesterases and
      human butyrylcholinesterase. All these structures reveal a negative external
      surface potential, in the area around the entrance to the active-site gorge, that
      becomes more negative as the rim of the gorge is approached. Moreover, in all
      cases, the potential becomes increasingly more negative along the central axis
      running down the gorge, and is largest at the base of the gorge, near the active
      site. Ten key acidic residues conserved in the sequence alignments of AChE from
      various species, both in the surface area near the entrance of the active-site
      gorge and at its base, appear to be primarily responsible for these potentials.
      The potentials are highly correlated among the structures examined, down to
      sequence identities as low as 35%. This indicates that they are a conserved
      property of the cholinesterase family, could serve to attract the positively
      charged substrate into and down the gorge to the active site, and may play other
      roles important for cholinesterase function.

PMID- 9640564
TI  - Transcanalicular laser-assisted revision of failed dacryocystorhinostomy.
AB  - BACKGROUND AND OBJECTIVE: Despite the high success rate of external
      dacryocystorhinostomy (DCR), recurrent tearing after DCR can be troublesome. The
      authors performed transcanalicular revision in 6 patients with failed DCR.
      PATIENTS AND METHODS: With the use of a continuous wave Nd:YAG laser with a
      sclerostomy probe, the internal ostium was reopened by a transcanalicular
      approach. The authors applied 0.4 mg/ml of mitomycin-C around the opening for 5
      minutes intranasally and inserted a silicone tube as a stent. RESULTS: A total of
      7 operations were performed in 6 patients. The operation was successful after the
      first revision in 5 of the 6 patients, but 1 of the patients required a second
      procedure. CONCLUSIONS: The transcanalicular laser-assisted revision has several
      advantages. It is simple and fast, skin incision is avoided, there is good
      hemostasis, it is less traumatic, and there is less postoperative morbidity.

PMID- 9640565
TI  - Combined intraocular and strabismus surgery.
AB  - BACKGROUND AND OBJECTIVE: To study the results of combined intraocular and
      strabismus surgery. PATIENTS AND METHODS: Combined surgery was done in 14
      patients. In 10 of these patients, cataract and strabismus surgery were combined.
      One had a penetrating keratoplasty, and another required placement of a glaucoma
      valve implant. In one patient trabeculectomy, pupilloplasty, and lensectomy were
      done, and one patient needed repair of a leaking bleb. RESULTS: The strabismus of
      most patients was significantly improved. Eleven patients (79%) were orthophoric
      +/- 10 prism diopters (PD). Visual outcome was good in patients with no
      structural abnormalities who were compliant with occlusion therapy, if
      applicable. CONCLUSIONS: Combined intraocular and strabismus surgery has a
      success rate comparable with that of standard strabismus surgery.

PMID- 9640566
TI  - Comparison of pain, motility, and preoperative sedation in cataract
      phacoemulsification patients receiving peribulbar or sub-Tenon's anesthesia.
AB  - BACKGROUND AND OBJECTIVES: The authors hoped to reduce the need for preoperative
      sedation and intravenous pain medication during cataract surgery by converting
      from peribulbar anesthesia to sub-Tenon's anesthesia. PATIENTS AND METHODS: A
      consecutive series of 2453 cataract patients' charts were reviewed. Each patient
      had previously watched a videotape explaining the anesthetic method to be used.
      Requests for preoperative sedation were compared between patients who received
      peribulbar or sub-Tenon's anesthesia. A sample of 200 charts of nonsedated
      patients were reviewed to compare intraoperative pain and motility. RESULTS:
      Intraoperative freedom from pain was reported by 91% of the peribulbar patients
      and 99% of the sub-Tenon's patients. Preoperative sedation was reduced from 26%
      of the peribulbar patients to 6.7% of the sub-Tenon's patients. CONCLUSIONS: Sub
      Tenon's anesthesia provided excellent intraoperative pain relief and reduced the
      need for preoperative sedation, making it a satisfactory anesthetic technique for
      patients undergoing cataract phacoemulsification in an ambulatory surgery
      facility.

PMID- 9640567
TI  - Intraocular pressure in nonglaucomatous eyes with pseudoexfoliation syndrome
      after cataract surgery.
AB  - BACKGROUND AND OBJECTIVE: To investigate the course of the intraocular pressure
      (IOP) in nonglaucomatous patients with pseudoexfoliation (PSX) syndrome after
      cataract surgery. PATIENTS AND METHODS: In a prospective age-matched controlled
      clinical study, 23 consecutive patients with PSX were studied and compared with a
      control group of 23 patients. The IOP was measured by applanation tonometry
      preoperatively, and postoperatively on day 1, after 4 weeks, and after 6 months.
      All patients were operated on with a self-sealing 7-mm scleral tunnel incision,
      phacoemulsification, and posterior chamber intraocular lens (IOL) implantation.
      RESULTS: Preoperatively the IOP was similar between both groups (P = .962). At
      the first postoperative day the IOP was below 22 mm Hg in all cases. After 4
      weeks and 6 months a mean decrease of 3.88 mm Hg (P = .001) in the control group
      and of 3.15 mm Hg (P = .002) in the PSX group was observed; this difference was
      not statistically significant (P = .543). CONCLUSIONS: At 1 day postoperatively
      no pressure increase was observed in the eyes with PSX after scleral tunnel
      incision and phacoemulsification. Six months after cataract extraction with IOL
      implantation, the tension level decreased in the presence of PSX similarly as in
      normal eyes.

PMID- 9640568
TI  - The effect of 1% apraclonidine on intraocular pressure after cataract surgery.
AB  - BACKGROUND AND OBJECTIVE: To measure the effect of 1% apraclonidine hydrochloride
      eyedrops on intraocular pressure (IOP) after cataract surgery. The effects of two
      different dosage regimens, once before surgery or once before and after surgery,
      were studied. PATIENTS AND METHODS: Patients scheduled for extracapsular cataract
      extraction and artificial lens implantation were randomly assigned to three
      groups: group A had a placebo treatment (n = 18), group B had one drop of 1%
      apraclonidine 1 hour before surgery (n = 16), and group C had one drop of 1%
      apraclonidine 1 hour before surgery and 1 drop at the end of surgery (n = 17).
      Two percent hydroxy-propyl-methyl-cellulose was used as the viscoelastic
      substance. The preoperative IOP and the IOP 6 hours postoperatively in each
      patient were compared. The paired Student's t test was used to compare IOP before
      and after surgery. The study design was a randomly assigned, double-masked
      controlled clinical trial. RESULTS: In group A (placebo) and group B
      (apraclonidine before surgery), there was a significant increase in IOP (mean IOP
      increase 11.2 +/- 9.9 mm Hg SD, range -4 to 32, P = .00017, and 9.4 +/- 7.4 mm Hg
      SD, range -3 to 24, P = .00014, respectively). In group C (apraclonidine 1 hour
      before and immediately after surgery), the increase in IOP was not significant
      (mean IOP increase 5.1 +/- 11.5 mm Hg SD, range -10 to 28, P = .084). A
      postoperative IOP of more than 40 mm Hg applanation tension was reached by two
      patients in group A, one patient in group B, and two patients in group C.
      CONCLUSION: Although 1% apraclonidine eye-drops instilled 1 hour before and
      immediately after extracapsular cataract extraction with artificial lens
      implantation may help prevent a statistically significant increase in IOP after
      the operation, 2 of the 17 patients still had IOPs greater than 40 mm Hg 6 hours
      postoperatively. Apraclonidine applied only before surgery did not prevent a
      statistically significant increase in IOP.

PMID- 9640569
TI  - Topical tissue plasminogen activator appears ineffective for the clearance of
      intraocular fibrin.
AB  - BACKGROUND AND OBJECTIVE: To determine the efficacy of topical tissue plasminogen
      activator (tPA) for the resolution of postoperative or inflammatory intraocular
      fibrinous exudates. PATIENTS AND METHODS: Each treatment consisted of drops of 1
      mg/ml tPA given 9 times 5 minutes apart. Records were reviewed and the results at
      24 and 48 hours were recorded. Sixty-two patients had a total of 94 treatments.
      RESULTS: Fibrin exudates following intraocular surgery in 34 patients were
      treated 44 times. In 6 patients there was a positive result. Fibrin associated
      with intraocular infection was treated in 9 patients. None showed clear
      improvement. Nineteen patients had a total of 34 treatments for poorly controlled
      intraocular pressure (IOP) after glaucoma surgery. Five patients showed adequate
      control of the IOP, 12 did not change, and 2 had a questionable improvement.
      Eleven patients had adequate IOP control after additional treatment. Seven
      required suture lysis, 2 ab interno bleb revision, and 2 YAG capsulotomy or
      iridotomy to reduce the IOP to an acceptable level. CONCLUSIONS: Within the
      limits of this retrospective study and taking into account that fibrin may
      resolve spontaneously, it appears that topical tPA drops are not effective for
      the liquefaction of intraocular fibrin after surgery or in association with
      intraocular inflammation. They did not improve IOP control after glaucoma
      surgery.

PMID- 9640570
TI  - The effect of mitomycin-C on postoperative corneal astigmatism in trabeculectomy
      and a triple procedure.
AB  - BACKGROUND AND OBJECTIVE: The authors attempted to determine the effect of
      mitomycin-C (MMC) on postoperative corneal astigmatism in patients who underwent
      trabeculectomy or a triple procedure (trabeculectomy, extracapsular cataract
      extraction, and intraocular lens implantation). PATIENTS AND METHODS: Using the
      vector analysis method, the authors measured the postoperative induced
      astigmatism of 76 eyes in 59 patients who underwent trabeculectomy or a triple
      procedure with or without the application of MMC. Postoperative induced
      astigmatism corresponding to the 180 degrees axis was compared between the two
      groups. RESULTS: The patients who underwent trabeculectomy with or without MMC
      showed a mean induced astigmatism of -1.01 D and -2.63 D, respectively, after 1
      month (P < .05), and 0.34 D and -1.42 D after 12 months (P < .05). Those who
      underwent a triple procedure with or without MMC showed a mean induced
      astigmatism of -1.81 D and -4.50 D, respectively, after 7 days (P < .05), and
      1.73 D and -0.13 D, respectively, after 12 months (P < .05). The entire amount of
      postoperative against-the-rule astigmatic shift was similar between the with-MMC
      group and the without-MMC group. The against-the-rule astigmatic shift of the
      group without MMC reached a plateau after 3 months. However, the group with MMC
      showed continuous against-the-rule astigmatic shift until 12 months. CONCLUSION:
      This study suggests that MMC induces less with-the-rule astigmatism in early
      postoperative periods and continuous against-the-rule shift after 3 months
      following a trabeculectomy or a triple procedure.

PMID- 9640571
TI  - Long-term results of excimer laser photorefractive keratectomy in high myopia: a
      preliminary report.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the results of 193-nm excimer laser
      photorefractive keratectomy (PRK) performed on highly myopic eyes with a follow
      up of at least 2 years. PATIENTS AND METHODS: Fifty-three eyes of 41 patients
      were treated with a myopic PRK for an attempted correction ranging between -8 and
      -17 D (mean -10.9 +/- 2.8 SD). RESULTS: The follow-up ranged from 24 to 60 months
      (mean 34.1 months +/- 10 SD). Fifty-three percent of the eyes achieved a
      refraction within +/- 2 D of the planned correction, with a refractive error
      greater than 4 D in 21% of the treated eyes. The uncorrected visual acuity was
      20/40 or better in 45% of the eyes. There were no significant opacities in 85% of
      the eyes examined. A second treatment was performed on 5 eyes. CONCLUSION: The
      results suggest that excimer laser PRK is a safe and relatively effective
      alternative for treating highly myopic eyes, and its effects are stable over a
      long period of time.

PMID- 9640572
TI  - Lack of effect of prophylactic gentamicin treatment on intraocular and
      extraocular fluid cultures after pars plana vitrectomy.
AB  - BACKGROUND AND OBJECTIVE: To analyze the effect of preoperative prophylatic 0.3%
      gentamicin sulfate eyedrops on intraocular and extraocular fluid cultures after
      pars plana vitrectomy. PATIENTS AND METHODS: Forty consecutive patients
      undergoing pars plana vitrectomy were randomly assigned to receive either 0.3%
      gentamicin eyedrops or placebo preoperatively. Fluids from the vitreous cavity
      and from the conjunctival sac were collected for bacteriologic studies. RESULTS:
      Positive cultures from extraocular fluids were obtained in 30.4% of the
      gentamicin group and 35.3% of the placebo group (P = .75). Furthermore, 1 (3%) of
      40 cultures of intraocular fluid and 13 (33%) of 40 cultures of extraocular fluid
      were positive. Culture growth positivity was not influenced by the patients' age,
      by diabetes, or by the duration of the operation. CONCLUSIONS: Prophylactic
      gentamicin treatment by the method applied in this study is not effective on
      reducing growth positivity. Contaminated extraocular fluid may play an important
      role in the pathogenesis of bacterial endophthalmitis following pars plana
      vitrectomy.

PMID- 9640573
TI  - In vitro evaluation of the efficacy of the capsular tension ring for managing
      zonular dialysis in cataract surgery.
AB  - BACKGROUND AND OBJECTIVE: In vitro evaluation of the capsular tension ring for
      managing zonular dialysis in cataract surgery. MATERIALS AND METHODS: Pig and
      cadaver eye models were used in this study. Lens material was removed with
      phacoemulsification, then the zonules were cut in one quadrant of the meridian to
      induce capsular bag decentration. Posterior chamber intraocular lenses (PC IOLs)
      were implanted into the bag with or without the tension rings. The IOL and the
      tension ring positions were viewed using the Miyaki technique. PC IOLs were also
      implanted into isolated capsular bags with or without tension rings, and bag
      configuration was examined. RESULTS: The IOL decentration was observed when the
      IOLs were implanted into the eyes without zonular support in one quadrant of the
      meridian. No IOL decentration was observed when the tension ring and the IOL were
      implanted together. When only the IOLs were inserted into the isolated bags they
      became oval, whereas the circular bags were preserved when both the IOL and the
      tension ring were placed in-the-bag. CONCLUSION: The authors' in vitro model
      demonstrated that the capsular tension ring maintained the circular contour of
      the capsular bag and IOL centration in the eyes with broken zonules. The results
      suggest that capsular tension rings may provide an alternative means to manage
      zonular dialysis during phacoemulsification and PC IOL implantation.

PMID- 9640574
TI  - Blood velocity in an experimental iris tumor.
AB  - BACKGROUND AND OBJECTIVE: Greene strain melanoma was implanted into the irides of
      eight nonpigmented rabbits to evaluate the blood flow in tumor vasculature.
      MATERIALS AND METHODS: Conventional scanning laser ophthalmoscopy was used in
      conjunction with fluorescent microsphere angiography (FMA). Changes were
      documented on SVHS videotape for later analysis. Individual microsphere movement
      was tracked through the tumor vessels. Subsequently, blood velocity measurements
      were taken. RESULTS: The tumor vessels were poorly organized and inefficient.
      Tumor blood velocity was up to 2.5 times slower compared with normal blood
      velocity in the unaffected iris of the same eye of the same rabbit (P = .05).
      Tumor blood flow could be qualitatively visualized in real time in the liver
      rabbit model. CONCLUSION: The ability to visualize fluorescent microspheres
      within the poorly organized tumor vasculature coupled with the reduced blood
      velocity in the tumor helps to explain the success of hyperthermic tumoricidal
      therapy, and may allow for development of more efficient and selective drug
      delivery systems and tumoricidal agents.

PMID- 9640575
TI  - Phacomorphic glaucoma associated with choroidal melanoma.
AB  - Patients with phacomorphic glaucoma present with mature cataract, shallowing of
      the anterior chamber, and angle-closure glaucoma. The opaque ocular media due to
      cataract formation usually precludes visualization of the posterior segment of
      the affected eyes. The authors describe a 65-year-old man who presented with
      reduced vision and clinical findings typical of phacomorphic glaucoma.
      Preoperative ultrasonography revealed an intraocular tumor, and magnetic
      resonance imaging showed a high signal intensity in T1-weighted images and a low
      signal intensity in T2-weighted images consistent with choroidal melanoma.
      Histopathologic examination of the tumor after enucleation confirmed the
      diagnosis. The clinical findings characteristic of phacomorphic glaucoma may be
      associated with choroidal melanoma. Ultrasonography or other imaging studies
      should be performed on eyes with phacomorphic glaucoma and opaque ocular media to
      allow timely detection of any mass lesion and to guide appropriate surgical
      management.

PMID- 9640576
TI  - Optic nerve sheath decompression in pediatric pseudotumor cerebri.
AB  - The authors report a retrospective review of two cases of optic nerve sheath
      decompression in children (age younger than 16 years) and review the literature
      on the procedure. Two children underwent optic nerve sheath decompression. Optic
      disc edema resolved in both eyes after surgery. Some degree of visual improvement
      was obtained in one eye of each patient after surgery, but one eye was unchanged
      in one patient and one eye of the other patient had worsening of visual acuity
      after surgery. Neither patient suffered any systemic complications from the
      procedure. Of 12 patients in the literature (including these 2 patients), 66%
      experienced improved visual acuity following optic nerve sheath decompression,
      33% had improvement in visual field, and 17% suffered worsening of visual acuity
      and visual field after surgery. Although optic nerve sheath decompression is a
      relatively safe and effective treatment for visual loss due to papilledema in
      adults, significant complications, including further visual loss, may occur. The
      experience with this procedure in children is limited, but retrospective data
      suggest that the safety and efficacy of the procedure may be comparable with that
      in adult patients.

PMID- 9640577
TI  - Blinding eye injury during a rock concert.
AB  - A 17-year-old girl attended a rock concert where promotional compact discs were
      being thrown into the audience as prizes. She suffered an extensive corneoscleral
      laceration with vitreous hemorrhage and retinal detachment when a compact disc
      struck her in the eye. An alternative, safer method must be used for distributing
      compact discs as prizes.

PMID- 9640578
TI  - Transscleral fixation of a dislocated silicone plate haptic intraocular lens via
      the pars plana.
AB  - A method for transscleral fixation of silicone plate haptic posterior chamber
      intraocular lenses (PC IOLs) via the pars plana is described. One 10-0
      polypropylene transscleral suture passed through the sclera and the PC IOL hole
      and a similar suture passed through the sclera only were withdrawn outside the
      eye thorough the pars plana and tied together. Pulling up the scleral end of one
      suture placed the PC IOL haptic in the sulcus and the knot was pulled outside the
      eye. Perfluorocarbon liquid was used during the procedure to safely manipulate
      the PC IOL. The PC IOL was well centered at 3 months of follow-up. Posteriorly
      dislocated silicone plate haptic PC IOLs can be safely sutured to the sclera via
      the pars plana by this method.

PMID- 9640579
TI  - Activities and well-being in older age: effects of self-concept and educational
      attainment.
AB  - The positive effect of activities on well-being is proposed to be mediated by
      self-conceptualizations and facilitated by socioeconomic status. The hypothesized
      processes were estimated with LISREL VIII using data from a large cross-sectional
      survey with a sample of 679 adults aged 65 and older who were representative of
      older adults living in the Detroit area. Findings indicate that the frequency of
      performing both leisure and productive activities yields an effect on physical
      health and depression and that these effects are mediated in part by a sense of
      self as agentic, but less clearly by a sense of self as social. Furthermore,
      socioeconomic status, operationalized as formal educational attainment,
      facilitates the effect of leisure to a greater extent than that of productive
      activities.

PMID- 9640580
TI  - Five-year retention of the classically conditioned eyeblink response in young
      adult, middle-aged, and older humans.
AB  - Human participants who 5 years earlier participated in studies of acquisition of
      the classically conditioned eyeblink response to a tone conditioned stimulus (CS)
      and an air puff unconditioned stimulus (UCS) returned to the laboratory to test
      for retention of the conditioned response (CR). Retention consisted of 20 tone CS
      alone presentations. Young adult participants (23-31 years of age at the time of
      retention testing) showed good retention of the CR (45%), middle-aged
      participants (45-52 years) showed reduced retention (28%), and older participants
      (69-78 years) showed little evidence of retention (< 5%). Retention testing was
      followed by reacquisition of the CR in which the CS and the UCS were again
      paired. The ability to reacquire the CR also showed a decline with age. The data
      suggest that the CR can be retained over long intervals and that the degree of
      retention is age dependent.

PMID- 9640581
TI  - Predictors of eyeblink classical conditioning over the adult age span.
AB  - The major aim was to identify predictors of the large age differences that exist
      in eyeblink classical conditioning. Eyeblink conditioning was assessed in 190
      participants over the age range of 20-89 years, with 150 trained in the paired
      condition and 40 trained in the explicitly unpaired control condition. Timed
      interval tapping was used to assess cerebellar function. Blink reaction time and
      explicit learning and memory were also assessed. Stepwise multiple regression
      indicated that the effect of age accounted for the largest proportion of the
      variance, but the cerebellar measure also predicted eyeblink conditioning at a
      significant level. Reaction time and explicit memory measures did not account for
      a significant amount of the variance in eyeblink conditioning. Age-related
      effects in the cerebellum apparently affect timing and learning in normal adults.

PMID- 9640582
TI  - Effects of increased response dominance and contextual disintegration on the
      Stroop interference effect in older adults.
AB  - In the study we considered the ability of the relative speed of processing
      automaticity (RSOP-A) and contextual disintegration (CD) models of the Stroop
      interference effect to account for the age-related increase in Stroop
      interference typically observed in older adults. Findings from the first
      experiment were partially consistent with predictions of the RSOP-A model because
      response dominance was greater for older adults than for younger adults. However,
      the age-related increase in interference was independent of this increase in
      response dominance, suggesting that factors other than those postulated in the
      RSOP-A model contributed to the greater interference observed in older adults.
      Results of the second experiment were consistent with the CD model, which
      suggests that older adults had difficulty maintaining a color-naming strategy to
      guide task performance.

PMID- 9640583
TI  - The psychological refractory period: evidence for age differences in attentional
      time-sharing.
AB  - The authors report 2 psychological refractory period (PRP) experiments in which
      the stimulus onset asynchrony (SOA) between Task 1 and Task 2 was 150 ms, 250 ms,
      600 ms, and 1,100 ms for both younger and older adults. H. Pashler's (1994a)
      response-selection bottleneck theory predicts that SOA manipulations should not
      affect Task 1 performance, but that reaction time (RT) for Task 2 should increase
      as the SOA between the 2 tasks decreases (i.e., the classical PRP effect). In
      Experiment 1 (Task 1 = tone discrimination, Task 2 = dot location), older adults
      showed a larger PRP effect than younger adults did, although Task 1 RT was
      affected by SOA, suggesting that participants were grouping their responses on
      some trials. That is, participants were holding their response for Task 1 until
      they had completed processing Task 2, and then they responded to both tasks
      almost simultaneously. However, a subset of participants (11 younger adults and
      11 older adults) who showed no evidence of response grouping on Task 1 continued
      to show a larger PRP effect for older adults on Task 2. In Experiment 2 (Task 1 =
      dot location, Task 2 = simultaneous letter matching), older adults continued to
      show a larger PRP effect than younger adults for Task 2, and Task 1 performance
      was unaffected by SOA. Consequently, these experiments provide evidence that
      older adults (relative to younger adults) exhibit a decrement in time-sharing at
      the response-selection stage of processing. These results suggest that
      attentional time-sharing needs to be added to the list of topics examined in
      aging research on varieties of attention.

PMID- 9640584
TI  - Response latencies for false memories: gist-based processes in normal aging.
AB  - Three experiments have demonstrated that age-related increases in both
      probability and speed of false recognitions for word lists depended on the use of
      a gist-based memory strategy. When test conditions promoted a gist strategy, both
      younger and older participants were as likely to falsely recognize a thematically
      associated lure as to correctly recognize a studied item, and both groups were
      equally fast in making these decisions. However, when test conditions
      deemphasized a gist-based strategy, older adults were more likely than younger
      adults, and faster, to falsely recognize both strong and weakly associated lures.
      These findings suggest an age-related increase in reliance on gist-based
      processing that may underlie age differences in false memory.

PMID- 9640585
TI  - Stressors in highly valued roles, religious coping, and mortality.
AB  - This study examines the relationships among stress, religious coping, and
      mortality. It is hypothesized that religious coping will offset the effects of
      stressors arising in highly valued roles on mortality, but similar stress
      buffering effects will not emerge with events in less important roles. It is
      further predicted that the beneficial properties of religious coping will be
      especially evident among older adults with less education. Data from a nationwide
      survey of older adults (N = 819; M age = 73.8 years; 41% male) indicate that
      religious coping offsets the effects of stressors in highly valued roles on
      mortality, but only among older adults with less educational attainment (p <
      .05). In contrast, events in roles that are not valued highly do not have
      significant additive effects on mortality or significant interaction effects with
      religious coping.

PMID- 9640586
TI  - Adult age differences in the temporal characteristics of category free recall.
AB  - Two experiments are reported that examined the temporal structure of recall for
      categorizable word lists by younger and older adults. All participants showed
      response bursting, in which recall order is clustered by semantic category, with
      longer interresponse times (IRTs) appearing between categories than within
      categories. Experiment 1 demonstrated that older adults, even when matched to
      younger adults in overall accuracy, differed in the rate of increase of between
      category IRTs with output position, but not in within-category IRTs. Experiment 2
      showed that this interaction is eliminated when the names of the response
      categories are provided to the participants. Results are interpreted in terms of
      combined effects of an age-compromised episodic memory system (between-category
      IRTs) accompanied by a comparatively preserved semantic system (within-category
      IRTs) in healthy aging.

PMID- 9640587
TI  - Influences of cognitive support on episodic remembering: tracing the process of
      loss from normal aging to Alzheimer's disease.
AB  - Normal older adults, incident Alzheimer's disease (AD) patients, and prevalent AD
      patients were examined across a 3-year interval in episodic memory tasks that
      varied in terms of study time, organizability, and retrieval cues. There were
      marked overall preclinical deficits among the incident AD patients, although
      these patients were as effective as the normal older adults in utilizing more
      study time, organizability, and retrieval cues to improve memory at baseline.
      When these patients were diagnosed with AD at follow-up, they showed negligible
      gains from increased study time and organizability when memory was assessed with
      free recall, although they profited from the provision of retrieval cues. This
      pattern of results was also seen in the prevalent AD patients at both times of
      measurement. These results indicate that a general impairment of episodic memory
      may precede reductions in cognitive reserve capacity in the early development of
      AD.

PMID- 9640588
TI  - Post-event review in older and younger adults: improving memory accessibility of
      complex everyday events.
AB  - Recalling an event at 1 time often increases the likelihood that it will be
      remembered at a still later time. The authors examined the degree to which older
      and younger adults' memory for everyday events that they watched on a videotape
      was improved by later seeing photographs or reading brief verbal descriptions of
      those events. Both older and younger adults recalled more events, in greater
      detail, with than without review. Verbal descriptions enhanced later recall to
      the same degree as reviewing photographs. Younger adults generally gained more
      from review than older adults on measures of the absolute number of details
      recalled and when facilitation was assessed relative to a no-review control
      condition, but not when memory for reviewed events was expressed as a proportion
      of each individual's total recall. Post-event review has clear potential
      practical benefits for improving memory of older adults.

PMID- 9640589
TI  - The effect of age, retinal eccentricity, and speed on the detection of optic flow
      components.
AB  - Forty observers participated in a study examining the effect of age on the
      detection of motion in central and peripheral vision. Detection of lamellar
      (Experiment 1) and radial flow (Experiment 2) was measured for 20 younger
      observers and 20 older observers (10 men and 10 women in each group). Motion
      thresholds were measured for angles of 0 degree, 10 degrees, 20 degrees, and 40
      degrees off fovea. The results indicated significant differences between older
      and younger adults for both motion types. The effect of age was mediated by the
      gender of the observer as well as the retinal eccentricity of the display. Older
      women showed higher thresholds for lamellar flow at fovea, consistent with
      previous findings. The findings suggest that age-related changes in visual
      information processing are affected by changes in the temporal characteristics of
      the motion processing system. A model is proposed in which 2 different streams of
      processing are used for the recovery and use of motion information.

PMID- 9640590
TI  - Taking a computational approach to aging: the SPAN theory of working memory.
AB  - The decline of working memory capacity associated with normal adult aging is well
      known. What is less well established is the cause of this decline. One prominent
      proposal is that working memory decline is caused by a reduction in basic
      information-processing speed, but this account has lacked a demonstration that
      general slowing is computationally sufficient to produce a decrease in working
      memory capacity. This article presents a production system theory of working
      memory (SPAN) based on established mechanisms: slowing, decay, and displacement.
      Models of 2 tasks--digit symbol and computation span--which have been prominent
      in research on slowing, are presented in detail. These models demonstrate that
      slowing is sufficient to produce differences in these tasks, and they provide a
      quantitative match to observed young-old differences as well. This advance for
      slowing theory also demonstrates the viability of computational tools in aging
      research.

PMID- 9640591
TI  - Age, attention, expertise, and time-sharing performance.
AB  - Time-sharing efficiency and resource allocation from a group of pilots with
      expertise in time-sharing and a group of nonpilots (ages 20-79 years) were
      examined. Participants performed 5 dual tasks that represented different degrees
      of structural similarity as characterized by the structure-specific resource
      model. Age, expertise, and structural similarity were found to interactively
      affect time-sharing performance through attentional resources. Age-related
      deficits in time-sharing were evident under conditions of intense attentional
      demands and when precise control was required. Modest expertise modulation of the
      age effects is likely to increase with more domain-specific time-sharing. The
      structure-specific resource model provided a useful framework for interpreting
      the relationship between aging and time-sharing performance.

PMID- 9640592
TI  - Cancer incidence in Songkhla, southern Thailand, 1990-1994.
AB  - A population-based cancer registry of Songkhla was established by the Cancer Unit
      of Songklanagarind Hospital under the support of the IARC in 1990. The province
      is in the southern region of Thailand and has a population of 1.2 million. This
      study presents the average annual incidence rate of the provincial total and of
      the district level covering 1990-1994. It is aimed at providing a comprehensive
      picture of descriptive epidemiology of cancer in the province. Data were
      collected from all hospitals in the provinces. Analysis was done under the
      program provided by IARC. There were 3,973 invasive cancer cases in the period.
      The age-standardized rate for all cancers was 116.7 in males and 88.7 in females.
      Lung, oral cavity, liver, and esophagus were the main leading sites in males
      while the cervix and breast were outstanding in females. By comparison, the
      incidence of most cancers were lower than other registries in Thailand except for
      two cancer sites. The incidence of male oral cavity and esophagus cancers in
      males (ASR 10.7 and 8.5 respectively) were considerably higher. Na Mom, Hat Yai,
      Sadao and Muang were districts having a high incidence of cancer.

PMID- 9640593
TI  - Development of cancer registry in Phatthalung Hospital.
AB  - Evaluation of feasibility is required for development of a hospital-based cancer
      registry of Phatthalung Hospital. The completeness of case finding from in
      hospital sources was evaluated for cancer cases diagnosed from January 1, 1994 to
      December 31, 1994. Cancer patients were collected from a file of pathological
      reports and medical records in Phatthalung Hospital. Items in the registration
      form included identification, demographic data and the data specific to cancer.
      During the same period of time, all biopsy cases sent from Phatthalung Hospital
      were selected from the pathological record of the Department of Pathology,
      Songklanagarind Hospital and from the database of the cancer registry of
      Songklanagarind Hospital. Ninety cases with histological verification were
      identified either from Phatthalung or Songklanagarind sources. Twenty seven cases
      were male and 63 were female. Fifty records were identified from Phatthalung
      sources and 40 additional records from Songklanagarind sources. Identification of
      cancer cases only from Phatthalung sources represented only 56% of all
      histologically verified cases. The two most common primary sites in males were
      colon and prostate. The percentages were 18.5 and 11.1 respectively. Lung cancer
      accounted only for 7.4% of all histologically verified cases. The two most common
      primary sites in females were cervix uteri and breast which accounted for 31.7%
      and 23.8% respectively. There was too much failure of case identification by in
      hospital sources only. Songklanagarind sources were important for case findings.
      However, it is important that the medical records and filing system in
      Phatthalung Hospital should be improved.

PMID- 9640594
TI  - Contamination of soil with parasite eggs and oocysts in southern Thailand.
AB  - Soil contamination with parasite eggs and oocysts was surveyed in southern
      Thailand in December 1994 and September 1995. The survey areas were Hat Kai Tao
      Village in Phatthalung Province and a slum area in a city of Songkhla Province.
      We used a modification of the centrifugal floatation technique with sucrose
      solution (specific gravity, 1.200) to recover helminth eggs and protozoa oocysts.
      Overall, 10 genera and 11 species of parasite eggs and oocysts were recovered.
      They included eight species of nematoda eggs, one species of cestoda eggs, and
      two species of protozoan oocysts. The definitive hosts of these parasites are
      dogs, cats, sheep, lizards, humans, etc. The contamination rates in two areas at
      different occasions varied from 55% to 72% with an average of 64%. Contamination
      rates of Hat Kai Tao Village in beginning and end of the rainy seasons were 72%,
      and 55%, respectively. Although the contamination rate in the end of rainy season
      was higher than that in beginning of the rainy season, the difference was not
      statistically significant (p > 0.05). Of the 11 parasites recovered, six were
      infective to humans, of which, Trichuris trichura, Ascaris lumbricoides, and
      Toxocara species were predominant. The mean numbers of these eggs recovered in
      each test were more than 10. Therefore, the contamination was estimated to be
      more than an egg per gram of soil sample based on the recovery efficiency (40%)
      of this test. These results suggested that the soil in some parts of southern
      Thailand may be heavily contaminated by both animal and human feces.

PMID- 9640595
TI  - A case-control study of acute diarrheal disease among school-age children in
      southern Thailand.
AB  - We conducted a case-control study of school-age children in Phatthalung, a
      province in southern Thailand using a questionnaire to investigate associations
      of children's hygiene-related behavior and hygienic conditions in their homes
      with acute diarrheal disease. We compared 69 acute diarrhea (less than 7 days
      duration) cases that attended two hospitals in Phatthalung during August 1995 to
      June 1996 with 69 age-, sex- and address-matched controls in primary schools who
      had not suffered from diarrheal disease for the past one year before August 1995.
      Three factors were found to be significantly associated with acute diarrheal
      disease: farmer or gum planter as the occupation of father [Odds ratio (OR) 6.6;
      95% confidence interval (CI) 1.7-26.1, p < 0.01], installation of a refrigerator
      in children's homes (OR 0.2; CI 0.1-0.8, p < 0.05), and drinking untreated water
      (OR 2.3; CI 0.9-6.1, p < 0.1). There was no significant difference for sources of
      drinking water between cases and controls. Considering the data on drinking
      water, the results indicated that there are some problems with quality of sources
      of drinking water. The results also suggested that having a refrigerator could
      have preventive effects on acute diarrheal disease, while inadequate behavior and
      unhygienic environment in the homes of farmers and gum planters might be related
      to acute diarrheal among school-age children.

PMID- 9640596
TI  - Differential distribution of hepatitis C virus subtypes in Asia: comparative
      study among Thailand, Indonesia, the Philippines and Japan.
AB  - Hepatitis C virus (HCV) is currently classified into at least six major
      genotypes, each of which is further divided into a number of subtypes. It has
      been reported that prevalence of each subtype varies among different geographical
      regions of the world and that severity of liver disease and sensitivity to
      interferon treatment varies with different subtypes. The purpose of this study
      was to determine and compare the prevalence of each subtype among HCV isolates in
      different areas in Asia such as southern (Hat Yai) and northern (Chiang Mai)
      parts of Thailand, Indonesia (Surabaya), the Philippines (Manila) and Japan
      (Kobe). Sera were obtained from various groups of patients and tested for
      antibodies against HCV using second and/or third generation ELISA kits. RNA was
      extracted from anti-HCV-positive sera and reverse-transcribed into cDNA. The cDNA
      preparations were subjected to nested PCR to amplify NS5B and 5'-untranslated
      region (5'UTR) sequences. Amplified fragments were sequenced and subtypes of the
      isolates were determined based on sequence similarities with reported sequences.
      In Chiang Mai and Hat Yai, Thailand, HCV-3a, HCV-1a and HCV-1b were common in
      various populations. HCV type 6 variants were commonly found among blood donors
      and drug addicts in Chiang Mai, but not in Hat Yai. In Surabaya, Indonesia, HCV
      2a was frequently detected in blood donors, but less frequently in patients with
      chronic liver disease. In blood donors, HCV-1a, HCV-1b and HCV-1d were more
      strongly associated with elevation of serum aminotransferase levels than HCV-2a.
      HCV-1a was significantly more common in patients on maintenance hemodialysis than
      in blood donors or patients with chronic liver disease. HCV-1d was detected
      exclusively in Indonesia. Another unique subtype HCV-3g was found also in
      Indonesia, though less frequently than HCV-1d. In the Philippines, a vast
      majority of the isolates were either HCV-1a or HCV-1b. Thus, HCV subtype
      prevalence varies among different regions of Asia.

PMID- 9640597
TI  - Dengue viruses induce cell proliferation and morphological changes of endothelial
      cells.
AB  - Replication of dengue viruses (type 1, 2, 3 and 4) in vitro in endothelial cells
      from human umbilical cord vein was demonstrated by virus titers and
      immunofluorescent antibody studies. Both showed highest peak at Day 6 after
      inoculation and declined to origin at Day 14. Some of the cultured endothelial
      cells detached from the culture well. Most of these floating cells were rarely
      viable as shown by failure in trypan blue exclusion whereas the adhering cells
      are mostly viable. More frequent and higher intensity of immunofluorescent
      positive cells were found in the detached cells as compared to adhering cells.
      The virus titers in the supernatant and in the adhering cell population were
      comparable, although floating cells were maximally 26.2% of the total cultured
      endothelial cells. Many floating cells and occasional adhering cells had numerous
      blebs on their surface. Endothelial cell proliferation was markedly increased
      after virus inoculation as compared with the control. Increased number of mitotic
      cells was also observed in the dengue virus-endothelial cell culture. Comparing
      among the four types, dengue type 4 induced highest peaks of cell proliferation
      and cell mitosis at Day 10 after inoculation. Dengue type 2 had the highest virus
      titers both in adhering cells and in supernatant at Day 6 as compared with other
      types.

PMID- 9640598
TI  - Malaria protection in hereditary ovalocytosis: relation to red cell
      deformability, red cell parameters and degree of ovalocytosis.
AB  - In the culture of red cells with Plasmodium falciparum, erythrocytes from both
      Thai patients and subjects (patient's parents) with hereditary ovalocytosis have
      a protective effect against malarial infection. High percentage of ovalocyte (75
      100%) was found in patients whereas their parents had lower percentage (25-50%).
      Invasion index (II) and multiplication ratio (MR) of P. falciparum in these
      abnormal red cells from the patients were significantly decreased as compared to
      those in normal red cells (patients: II = 1.52 +/- 0.91, MR = 8.83 +/- 6.73;
      normal subjects: II = 4.45 +/- 1.51, MR = 25.23 +/- 6.25). This suggests that the
      red cells from these patients had significant degree of malaria protection. The
      significant protection was also shown in red cells from the parent group (II =
      1.86 +/- 0.81, MR = 15.69 +/- 3.50). Although the parents had lower ovalocyte
      percentage, degree of protection against malaria parasite was as effective as
      those found in patients with high ovalocytic red cells. This has been confirmed
      by statistical analysis showing nonsignificant difference in II value between the
      two groups. In contrast, red cells of both groups had poor deformability
      (deformability index, DI) as compared to the normal group. No statistically
      different DI values were demonstrated between the two. This indicates that poorly
      deformable red cells, not their ovalocytic shape, make a significant contribution
      to limitation of malaria parasite invasion. The MR values in patients were less
      than those found in the parent group but statistical analysis showed no
      significant difference. Reduced MR values were found with increased numbers of
      microcytic, hyperchromic and hypochromic red cells in patients.

PMID- 9640599
TI  - Recent advances in medical genetics: what we have done and what we will do.

PMID- 9640600
TI  - Genomic imprinting relevant to genetic diseases.
AB  - Genomic imprinting is a new concept proposed to explain unusual observations in
      early mammalian development, the occurrence of certain genetic diseases, genetic
      anticipation or incomplete penetrance, and tumorigenesis. The basic mechanism of
      the imprinting has remained obscure, although DNA-methylation, chromatin
      structure, and/or DNA replication may have a role. Genomic imprinting is a
      biological phenomenon determined by an evolutionally acquired, underlying system
      that may control harmonious development and growth in mammals. It is also
      relevant to the occurrence of some genetic disorders in man.

PMID- 9640601
TI  - Genotypic and phenotypic implications in paroxysmal nocturnal hemoglobinuria
      (PNH): a preliminary investigation.
AB  - The genetic and biochemical defects underlying paroxysmal nocturnal
      hemoglobinuria (PNH) have recently been elucidated. The deficiency of the surface
      expression of glycosylphosphatidylinositol (GPI)-anchored proteins caused by a
      somatic mutation of the PIG-A gene, an X-chromosomal gene that participates in
      the first step of the GPI anchor synthesis, has been shown to be responsible for
      PNH in all patients. The mutations of PIG-A studied to date are highly
      heterogeneous. They are however mainly of the frameshift type (61.5%). The
      characteristic abnormalities of PNH phenotypes has also been shown especially by
      DAF- and/or CD59-based fluorescent immunocytometry. A great degree of
      heterogeneity in the patterns and levels of expression of GPI-anchored proteins
      in various cell types was demonstrated indicating a discrepancy of lineage
      involvement. In this investigation, major blood cell populations, i.e
      erythrocytes and granulocytes were analyzed immunophenotypically, the mutations
      of PIG-A were identified by heteroduplex analysis and nucleotide sequencing and
      the consequences of PIG-A mutations were observed. All the mutations identified
      in 9 patients with PNH resulted in complete loss of function as clones of
      affected granulocytes completely negative for CD59 expression were shown in all
      patients. Interestingly, granulocytes in these patients contained variable
      proportions of affected cells varied from 50% to 100% and four of the patients
      had erythrocytes with diminished expression of GPI-anchored DAF and CD59
      coexisting with normal and completely negative cells. Immunophenotypic analysis
      of reticulocytes in peripheral blood of patients with PNH demonstrated the
      conserved patterns of DAF and CD59 expression in circulating erythroid cells and
      the discrepancies between granulocytic and erythroid lineages. These findings
      suggested that the characteristics of abnormal phenotypes which appear to be
      highly variable between different hematopoietic lineages are not solely caused by
      mutation of PIG-A but are influenced by other factor(s).

PMID- 9640602
TI  - Pyruvate kinase deficiency in an alpha-thalassemia family: first case report in
      Thailand.
AB  - In Thailand, the most common cause of chronic hemolytic anemia is thalassemia
      hemoglobinopathy. We report here a 10-year-old girl with pyruvate kinase (PK)
      deficiency who was initially diagnosed to have Hb H disease, like her sister. The
      patient had a history of neonatal jaundice which required blood exchange
      transfusion twice and phototherapy. She became anemic and regular blood
      transfusion was required since the age of 2 1/2 months. She was very anemic
      compared to her sister and was transfusion dependent. Besides, she never had red
      cell inclusion bodies, thus re-evaluation was performed. The diagnosis of red
      cell pyruvate kinase deficiency and the exclusion of Hb H disease was achieved
      after cessation of blood transfusion for 3 months. The family study also
      confirmed the diagnosis. The patient is now on high transfusion and iron
      chelation. She is doing well with mild splenomegaly.

PMID- 9640603
TI  - The frequency of fragile X syndrome among selected patients at Songklanagarind
      Hospital during 1991-1996, studied by cytogenetic and molecular methods.
AB  - Fragile X syndrome is the most common inherited form of mental disability, world
      wide. Main clinical features are cognitive deficit, speech difficulties, delayed
      development, autism, and particular physical characteristics. The syndrome can be
      cytogenetically diagnosed by the expression of chromosome X fragile site at band
      Xq27.3. At molecular level, the cause of the syndrome is defined as an abnormal
      expansion of CGG trinucleotide repeats in the 5'UTR of the FMR-1 gene as well as
      hypermethylation at the proximal CpG island. Study of fragile X syndrome at
      Songklanagarind Hospital during May 1991-June 1996 was herein reported. A total
      of 287 blood samples of 260 unrelated families were cytogenetically examined by
      using lymphocyte culture method with 2-4 different treatments. Frequency of
      positive fragile X cases was found to be 7 in 260 (2.7%). Among relatives of the
      positive ones, 13 individuals were also positive. Other types of chromosome
      abnormalities were detected in 13 cases (5%). For molecular study, DNA samples
      were obtained from 97 cases. Investigation of CGG repeat expansion was performed
      by PCR method. Abnormal expansion was identified as full mutation (> 200 repeats)
      and premutation (> 50-200 repeats). The abnormalities were found in 14
      individuals of 5 unrelated cases; 6 with full mutation and 8 with premutation. No
      molecular study on the two cytogenetic positive cases has been performed. In
      conclusion, a total of 50 individuals with fragile X abnormality has been
      documented: 18 affected cases and 32 carriers. Investigation of the remaining
      suspected members in positive families is in progress. The information and
      experience will lead to prevention of this genetic disease by prenatal diagnosis
      and elective abortion in Thailand.

PMID- 9640604
TI  - Screening for thalassemia: an economics viewpoint.
AB  - Thalassemia presents individual, social and economic burdens: a key question is
      whether medical and economic viewpoints converge or not. Using precise molecular
      probes, prenatal diagnosis of the various thalassemia genotypes is available in
      the case of parents who are known carriers, so identified because of a previous
      affected child or a positive family genetic history. However, the ideal option of
      prevention of the birth of a first affected child requires community screening.
      The only practical approach thereto is prenatal screening of women in early
      pregnancy at ante-natal clinics (ANC). The initial steps (OF, DCIP) are simple,
      cheap and easily coupled with standard prenatal procedures. In the second phase,
      spouse screening, compliance is suboptimal and involves non-routine opportunity
      costs. Subsequent steps (secondary screening of positive pairs, genotyping of
      positives, and fetal diagnosis [PND]) represent greater costs to provider and
      consumer, and, as they are relatively expensive, reduced compliance at each step
      if the major part of the economic burden (direct and indirect costs) is to be
      borne by the consumer. Thus, only a proportion of cases is likely to face the
      final decision to terminate pregnancy or not. Some broad estimates of costs of
      each phase (ANC-->PND) have been made for comparison with the estimated costs of
      case management of the several thalassemia disease classes for their projected
      lifetimes, while several more detailed studies are in progress to fine tune the
      real costs (direct and indirect) of diagnosis. In a purely economic sense the
      situation presents opportunity to consider trade-offs between PND and disease
      case management, in terms of benefit:cost ratio. Viewed from a health systems
      vantage point this ratio depends substantially on compliance, as the system must
      consider the cost of caring for all thalassemia cases, including those births
      which could have been avoided by optimal compliance. In ideal circumstances the
      rough estimates indicate a probable benefit:cost ratio > 1, supporting the notion
      of community-based screening. Such a result, however, compares procedures in a
      short, finite time frame (diagnosis) with a less predictable, longer life-time
      (case management), requiring bureaucratic flexibility (if the public provider is
      to pay) or family emotional/fiscal investment (if the consumer is to pay) or both
      (cost-sharing): either way there is an inescapable element of long term
      investment planning that requires squaring off of the emotional, social and
      fiscal ingredients in the equation. In this sense the thalassemia syndromes
      represent an example of decision-making pathways involved in assessing and
      handling chronic disease burdens at family, community and national levels: at the
      latter level regional incidence varies considerably, a geopolitical factor which
      may require differential demographic planning.

PMID- 9640605
TI  - An in vitro study on thalassemic erythroid precursors in liquid culture.
AB  - Thalassemia is an inherited hematological disorder which can generally be
      classified according to the affected globin imbalance (alpha- or beta-globin)
      into two main types, i.e. alpha-thalassemia and beta-thalassemia, respectively.
      There is a wide range of cellular abnormalities associated with thalassemic
      erythrocytes such as hypochromia, microcytosis, reduced cellular deformability
      and membrane oxidative damage. The red cell abnormalities lead to premature
      destruction with marrow erythroid hyperplasia and ineffective erythropoiesis. The
      abnormalities in thalassemic red blood cells have been found along the erythroid
      differentiation pathway other than the mature stage as previously shown in bone
      marrow erythroid precursors and in reticulocytes, the penultimate stage of
      erythroid differentiation. However, there is a lag in our understanding of the
      more primitive erythroid stages due to the difficult and hazardous marrow
      aspiration and heterogeneity of cells derived. We have utilized a novel method of
      Two-Phase Liquid Culture (TPLC) of beta-thalassemia/HbE erythroid precursors
      instead of conventional semisolid culture. This type of liquid culture can given
      higher cell yield with quite synchronous cell differentiation stages and easily
      be applied for other cellular analytical techniques. The peripheral blood
      mononuclear cells (PBMC) obtained from non-splenectomized and splenectomized beta
      thalassemia/HbE patients were first cultured in medium supplemented with 5637
      conditioned medium for a 6-day period (phase I) and then transferred to medium
      supplemented with recombinant human erythropoietin to allow the terminal
      differentiation of erythroid precursors (phase II). During the phase I or II, the
      cultured cells were periodically sampled to determine the cell number,
      cytocentrifuged on glass slides and stained with Wright stain for morphological
      assessment of their differentiation stages and analyzed flow cytometrically by
      staining with fluoresceinated anti-transferrin receptor (anti-CD71) and R
      phycoerythrin-conjugated anti-glycophorin A. After assessment by flow cytometry,
      the remaining stained cells were cytocentrifuged on glass slides and photographed
      by a fluorescent microscope and a laser scanning confocal microscope. The results
      of morphological assessment, flow cytometric analysis and microscopic pictures
      will be presented.

PMID- 9640606
TI  - Alpha-thalassemia incidence in southern Thailand by restriction endonuclease
      analysis of globin DNA from placental blood at Songklanagarind Hospital.
AB  - The incidence of alpha-thalassemia has been studied previously based on the
      levels of Hb Barts' in cord blood. This method is an inadequate indicator of
      alpha-thalassemia. Thus in this study we use DNA analysis to get more accurate
      data. Hb Barts' was detected in placental blood samples from 15.5% of 375 infants
      born at Songklanagarind Hospital. The white blood cell DNA of 300 samples was
      studied for alpha-globin gene deletions by hybridization of DNA fragments
      digested by the restriction endonuclease Eco RI with specific 32P-labled zeta
      globin gene probe. The incidence of alpha-thal 2 and alpha-thal 1 traits were
      12.0% and 4.3%, with the gene frequencies 0.0650 and 0.0217 for -alpha/and --/,
      respectively. The incidence of HB CS trait was 5.8%, with the gene frequency of
      0.0292 for alpha cs alpha/. We also found that the incidence of the triplicated
      zeta and triplicated alpha were 14.7 and 1.0%, with the gene frequencies of
      0.0733 and 0.0050 for zeta zeta zeta/and alpha alpha alpha/, respectively. The
      DNA lesion of alpha-thalassemia in the south is similar to the study of
      Tanphaichitr et al (1988) in central Thailand. Knowledge of alpha-globin gene
      deletion would be useful for prenatal diagnosis of Bart's hydrops to prevent
      toxemia of pregnancy in the south of Thailand.

PMID- 9640607
TI  - Red cell parameters in alpha-thalassemia with and without beta-thalassemia trait
      or hemoglobin E trait.
AB  - Eighty-five patients who attended at Ramathibodi Hospital during November 1994 to
      June 1996 were investigated for thalassemia genotype, hemoglobin (Hb) typing and
      blood cell parameters. All patients were screened primarily for complete blood
      count using the Technicon H*3 automated hematology analyzer and Hb typing using
      the automated HPLC. Their genotypes were evaluated by in vitro gene amplification
      using primers for detection of common alpha-thalassemic genes found in the Thai
      population. We found 45 cases out of 85 were alpha-thalassemia trait with A2A
      typing, 10 were normal, 7 were alpha-thalassemia trait complicated by beta
      thalassemia trait or HbE trait, 18 were HbH disease or HbH with Hb Constant
      Spring (HbH/CS), and 5 were AE Bart's disease. The alpha-thalassemia 1 trait had
      heterogeneity in red cell population as shown by increased red cell distribution
      width (RDW), the increased percent microcytic red cell (%Micro) and decreased
      mean cell volume (MCV). Red cell parameters in alpha-thalassemia 2 trait and HbCS
      trait were not significantly different from normal. The cases with coinheritance
      of alpha-thalassemia trait with beta-thalassemia trait or with HbE trait showed
      variation in their red cell parameters: one case showed less abnormal red cell
      parameters than those of uncomplicated alpha-thalassemia but the other two cases
      showed unimproved values. The homozygous alpha-thalassemia 2 showed similar red
      cell parameters to the alpha-thalassemia 1 trait. In conclusion, we can screen
      the alpha-thalassemia 1 trait and homozygous alpha-thalassemia 2 by using the
      simple red cell parameters such as the MCV and RDW; however, they must be
      confirmed for alpha-thalassemic genes. Unfortunately, red cell parameters of
      alpha-thalassemia 2 trait or HbCS trait were not different from those of normal
      subjects.

PMID- 9640608
TI  - Molecular and hematological characterization of HbE heterozygote with alpha
      thalassemia determinant.
AB  - Hemoglobin E and alpha-thalassemia are prevalent in Thailand. The chance that an
      individual heterozygous for HbE also carries an alpha-thalassemia determinant is
      high. In this individual, the amount of HbE and other hematological parameters
      may be differed from that of usual observation. In this study, a total of 132 HbE
      heterozygotes were screened for alpha-thalassemia 1 gene deletion by the
      polymerase chain reaction. Out of 132 cases, 71 could be completely analyzed for
      hematologic parameters. Forty-three of 88 cases with HbE less than 25% as
      measured using microcolumn chromatography were positive for this gene deletion.
      In twenty of these 43 alpha-thalassemia 1 positive cases, the average values of
      Hb, Hct, MCV, MCH, MCHC, RDW and HbE were 10.6 g/ dl, 33.1%, 64.8 fl, 21.0 pg,
      32.3 pg/dl, 18.6% and 17.4%, respectively. Eight of 9 alpha-thalassemia 1
      negative cases were positive for alpha-thalassemia 2 gene deletion in Southern
      blot analysis. In this later group, hematological parameters were similar to that
      of the former. Co-inheritance of the Hb Constant Spring gene has no direct effect
      on the level of HbE. No alpha-thalassemia 1 gene was detected in the remaining 34
      cases whose HbE were above 25%. The average amount of Hb, Hct, MCV, MCH, MCHC,
      RDW and HbE were 12.4 g/dl, 37.7%, 79.7 fl, 26.2 pg, 32.7 pg/dl, 25.8% and 28.5%,
      respectively. Therefore, screening for HbE level below 25% may be a convenient
      way of identifying parents of carrying alpha-thalassemia 1 determinant.

PMID- 9640609
TI  - Molecular basis of beta-thalassemia in Thai Muslim patients in the the south of
      Thailand.
AB  - Among a sample of 29 unrelated Thai Muslim children, a total of 37 beta
      thalassemia genes was identified and 33 out of 37 mutations (89%) were
      characterized giving 6 different mutations. Four mutations [IVS-1 nt 5 (G-C),
      codon 19 (A-G), codons 41/42 (-CTTT) and IVS-1 nt 1 (G-T)] account for 86%. IVS-1
      nt 5 (G-C) is the most common mutation found in Thai Muslim patients. Thai Muslim
      patients share the four most common mutations with Malays.

PMID- 9640610
TI  - Clinical, hematological and molecular features in Thais with beta-Malay/beta
      thalassemia and beta-Malay/HbE.
AB  - A total of 50 patients and relatives were studied comprising 12 cases of compound
      heterozygosity of beta-Malay and beta + thalassemia, 10 cases of compound
      heterozygosity of beta-Malay and beta degree thalassemia, 10 cases of beta-Malay
      and HbE and 18 cases of beta-Malay heterozygosity. Patients with beta-Malay and
      HbE had very mild clinical symptoms or were asymptomatic of thalassemia disease
      in the absence of blood transfusion. Homozygosity of beta-Malay produce mild
      clinical symptoms of thalassemic disease with normal facial characteristics and
      were not transfusion dependent. Patients with beta-Malay and IVS 1 nt 5 (G-C) had
      severe clinical symptoms, and were transfusion dependent. Patients with beta
      Malay and beta degree thalassemia had severe clinical symptoms, delayed weight
      and height in relation to age, were transfusion dependent and had classical
      features of thalassemic diseases.

PMID- 9640611
TI  - Molecular and hematological characterization of Hb Tak and Hb Pyrgos in Thailand.
AB  - Two hemoglobin variants that migrate abnormally on gel electrophoresis were found
      in four unrelated Thai individuals. One variant that migrate faster than HbA but
      more slowly than Hb Bart's was detected in two heterozygotes. Another abnormal Hb
      migrating between HbA2 and HbF was found in one heterozygote and one compound
      heterozygote with HbE. In all cases, no microcytic anemia was observed. PCR
      amplification and direct DNA sequencing established that the first variant was
      caused by a missense mutation at codon 83 (GGC-GAC) that leads to Gly to Asp
      substitution previously described as the Hb Pyrgos in a Greek boy. The second
      variant was caused by an AC insertion at the termination codon that leads to
      synthesis of elongated beta-globin chain known as the Hb Tak. Beta globin gene
      haplotype analysis demonstrated that each variant was found on the same
      chromosome background in Thai individuals. The simple non-radioactive DNA assays
      based on allele specific polymerase chain reaction for the detection of these two
      Hb mutations in a routine laboratory are described.

PMID- 9640612
TI  - Beta-globin gene haplotypes in some minor ethnic groups in Thailand.
AB  - In order to provide population genetic data of various ethnic groups in Thailand,
      we have determined the type of hemoglobin by electrophoresis and the beta-globin
      gene haplotypes by PCR followed by restriction digestion in five small ethnic
      groups namely hill tribes, PhuTai, Chong, Lao Song and Sakai inhabiting in the
      north, northeast, east, central and south of Thailand, respectively. In each
      group, in addition to HbA and HbA2, the HbE, the most common hemoglobinopathy in
      Southeast Asia was detected at 2.5%, 51.6%, 84.0%, 8.6% and 11.8%, respectively.
      Haplotype analysis demonstrated that in all groups the beta A-globin gene was
      associated with various haplotypes and beta-globin gene frameworks. However, beta
      E -globin gene was associated with haplotypes ((-)+(-)+ + +(-)) and ((+)-(-)-(
      )+(-)) on the beta-globin gene framework 2 in all ethnic groups except in Chong
      people whose the beta E-globin gene was mostly linked to haplotype ((-)+(-)++(
      )+) and beta-globin gene framework 3 which was commonly found among Cambodian. It
      appears therefore that the Chong population is more related to Cambodian than
      Thai.

PMID- 9640613
TI  - Analysis of beta-thalassemia mutations and beta-locus control region
      hypersensitive sites 2, 3 and 4 in southern Thailand.
AB  - beta-Thalassemia mutations in 221 chromosomes of unrelated southern Thai patients
      were analyzed. Using dot blot hybridization of PCR amplified DNA with 15 allele
      specific oligonucleotide probes for beta-thalassemia mutations 196/221 (89%) of
      the alleles were characterized. Ten mutations were identified, of which six
      [codon 41/42 (TTCTTT-TT), IVS1 nt5(G-C), codon 19 (AAC-AGC), codon 17 (AAG-TAG),
      IVS1 nt1(G-T), -28 TATA (A-G)], accounted for 85%. Among the 25 uncharacterized
      alleles, 15 were analyzed by automated fluorescent DNA sequencing of the whole
      beta-globin gene with normal results in 7 alleles. Four mutations, previously
      described were detected in 8 alleles. They were a G-A at IVS1 nt1 in one
      heterozygote, a G-T at IVS1 nt1 in one heterozygote, codon 15 (TGG-TAG) in two
      heterozygotes and poly A(AATAAA-AATAGA) in two homozygotes. The polyadenylation
      mutations, previously demonstrated in the Malaysian population have been first
      detected in Thailand. It is remarkable that the IVS1 nt1 (G-A) mutation,
      previously reported in the Mediterranean population has been found only in the
      south of Thailand. This mutation was probably imported from Portugal. In former
      times the Portuguese had settled in Phuket in southern Thailand. In order to find
      a causative mutation in the rest of 7 true unknowns we performed direct DNA
      sequencing of the core fragments of the beta-Locus Control Region Hypersensitive
      Sites (LCR HS) 2,3 and 4 in these 7 samples. DNA sequencing of HS2 and HS3
      fragments showed normal results. The heterozygote A/G was present in the
      palindromic sequence of the LCR HS4 (TGGGGACCCCA) in 6 beta-thalassemia samples.
      The same heterozygote A/G was found in 5/12 normal subjects. The allele frequency
      of A (0.79) is obviously higher than that of G (0.21). This could be due to the
      stability of the palindromic structure. When an A is in the middle of the
      palindromic sequence, the hairpin structure is formed. In contrast the hairpin
      structure disappears when a G is in the middle of the palindromic sequence. This
      structure is not further symmetric and may not be so stable as the hairpin
      structure. beta-Thalassemia mutations in southern Thailand are very heterogeneous
      and their distribution is different from other parts of the country.

PMID- 9640614
TI  - Detection of thalassemia genes using smeared blood film or leukocytes adhering to
      polysthylene fibers.
AB  - Presently genetic analyses for thalassemia types require relatively large amounts
      of heparinized blood (5 to 10 ml), and transport as well as degeneration of these
      sample is a problem in the developing world. We have developed a new method to
      simplify this procedure and obtain DNAs from small specimens. As experimental
      materials, thinly smeared blood on a glass slide or blood filtered with and
      adhered on polysthylene telephtalate (PST) fibers were used. These materials
      could be safely stored without interfering with DNA extraction for up to 3
      months. The slide materials were digested with proteinase K, and DNA was
      extracted with Tris-EDTA-phenol:chloroform and precipitated with absolute
      ethanol. The PST specimens were washed with physiologic saline and treated in the
      same manner as described above. Products were easily amplified by PCR and
      digested with restriction endonucleases for beta thalassemia typing as well as
      for HLA-DQA1 gene typing. Results obtained by this method correlated well with
      previously reported incidences for thalassemia and HLA-DQA1 types in Thailand.
      This method can be used in the routine laboratory because it allows for stable
      and biosafe genetic analyses.

PMID- 9640615
TI  - Difference in pattern of erythropoietin response between beta
      thalassemia/hemoglobin E children and adults.
AB  - Thalassemia is one of the most common genetic disorders in Thailand. The
      thalassemic patients have many pathophysiologic changes secondary to chronic
      anemia. During these last few years there have been many trials to cure or
      improve the anemic condition in thalassemia by using various agents, including
      erythropoietin (EPO). Thus it is very important to understand the EPO response to
      different degree of anemia in the thalassemic patients. In this study we
      evaluated the EPO status in 53 beta-thalassemia/HbE patients, from 4-61 years
      old, by enzyme-linked immunosorbent assay. The results showed that the levels of
      EPO in beta-thalassemia/HbE patients were much higher than in normal control
      subjects: mean +/- SE = 527 +/- 183.20 and 3.45 +/- 0.47 mIU/ml respectively. The
      reverse correlation between the levels of EPO and hematocrit (r = -0.704) was
      also observed. There was also a tendency to have higher levels of EPO in beta
      thal/HbE children than in adults, although this was statistically insignificant.
      The observed versus predicted levels of EPO (log O/P ratio) showed that most
      patients had good EPO response to the degree of anemia. However, inappropriate
      decrease of EPO response was observed in 8/40 adult patients. The EPO levels in
      these patients were not correlated with any physical or laboratory studies,
      including kidney function. We thus propose that if EPO is to be considered as one
      of the alternative treatment to the thalassemic patients, in the future, it may
      benefit only the patients with low EPO levels.

PMID- 9640616
TI  - Pulmonary microthromboembolism by injection of sonicated autologous blood in
      rabbits with splenic artery ligations.
AB  - Chronic pulmonary thromboembolism (PTE) has been reported to play an important
      role in cardiac failure in thalassemic patients after splenectomy. However, the
      mechanism of PTE in these patients remains unclear. In this study, we attempted
      to establish an animal model of PTE seen in thalassemic patients after
      splenectomy. We divided New Zealand white rabbits into three groups: Group 1 was
      injected sonicated blood, II was injected non-sonicated blood after ligation of
      the splenic artery, and III was injected sonicated blood after ligation of the
      splenic artery. After injection of the sonicated blood, we counted the platelet
      number until 1 hour and the rabbits were sacrificed for histological examination.
      Platelets significantly decreased in number immediately after injection of the
      sonicated blood in Groups I and III. Many pulmonary thromboemboli composed mainly
      of platelets were found in Group III but not in other groups. These pathological
      changes seem to be partly similar to those of thalassemic patients after
      splenectomy. This animal model is thought to be useful to study the pathogenesis
      of pulmonary thromboembolism, especially in thalassemic patients after
      splenectomy.

PMID- 9640617
TI  - Possible evidence of endothelial cell activation and disturbance in thalassemia:
      an in vitro study.
AB  - Activation of vascular endothelium is considered as an important facet of
      inflammation, thrombosis, and vasculitis. Activated endothelial cells express a
      number of immunologically relevant surface markers which are not detected in
      dormant condition. These surface markers on endothelial cell may involve in
      adhesion reaction and migration of blood cell components. We demonstrated
      increased level of the soluble adhesion molecules in circulating blood of both
      alpha- and beta-thalassemic patients. These adhesion molecules are theoretically
      known to be released from endothelial cells. The adhesion molecules included
      soluble Intercellular Adhesion Molecule-1 (sICAM-1), soluble E-Selectin (ELAM-1),
      soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1), and von Willebrand Factor
      (vWF). The levels of these adhesion molecules were measured in serum from 32
      thalassemic patients and 10 control healthy subjects. As compared to normal,
      increased sICAM-1 was found in beta-thal/HbE patients with non-splenectomy; BE-NS
      (p = 0.002), increased ELAM-1 in beta-thal/HbE patients with splenectomy; BE-S (p
      = 0.01) and HbH with Hb Constant Spring; HbH/CS (p = 0.001), and increased sVCAM
      1 in BE-NS; (p = < 0.0001) and BE-S (p = 0.002). Significant increase in von
      Willebrand Factor (vWF), a marker for endothelial cell, was shown in BE-S (p =
      0.04) as compared to normal. Adhesion molecules were also markedly demonstrated
      in the supernatant of in vitro culture of human vascular endothelial cell in the
      presence of 30% thalassemic serum, and these adhesion molecules were also
      detected on the surface of the cells by using the technic of laser scanning
      confocal microscope and direct immunofluorescence.

PMID- 9640618
TI  - Morphological alterations and apoptosis of endothelial cells induced by
      thalassemic serum in vitro.
AB  - Vascular complications such as lung thromboembolism and leg ulcer have been
      observed in thalassemic patients. Recently, our group has reported impaired
      proliferation of endothelial cells (ECs) after exposure to alpha- and beta
      thalassemic sera in a culture system. This study was undertaken to detect
      apoptotic phenomena of ECs in the presence of alpha- and beta-thalassemic serum.
      ECs from normal human umbilical cord vein were exposed to 30% thalassemic serum
      in vitro and morphological changes were observed by using phase contrast,
      fluorescence and scanning electron microscopy. Such treated ECs presented
      morphological characteristics of apoptosis as shown by the appearance of compact
      cytosol, membrane blebbing, margination of nuclear matrix, condensed nuclei, and
      fragmented bodies. The majority of apoptotic cells was in the floating
      population. Similar morphological changes were also observed by treating ECs with
      hydrogen peroxide in the concentration range of 0.1-10 mM.

PMID- 9640619
TI  - Thalassemic serum inhibits endothelial cell mitosis in vitro.
AB  - Human umbilical vein endothelial cells were cultured in vitro using Iscove's
      Modified Dulbecco's Medium (IMDM) supplemented with either pooled normal human
      serum, or pooled thalassemic serum, or autologous umbilical cord serum, or fetal
      bovine serum. The mitotic activity was determined under the inverted phase
      contrast microscope and the number of mitotic cells was counted. Our results
      showed that the mitotic cells decreased in endothelial cell culture with
      thalassemic serum as compared with normal human serum, autologous umbilical cord
      serum or fetal bovine serum. The percentage of mitotic cells decreased on day 3
      in the presence of beta-thalassemia/HbE serum from both splenectomized and non
      splenectomized patients as compared with normal or autologous umbilical cord
      serum. In the presence of alpha-thalassemic serum, a similar outcome was also
      observed. From this study we can conclude that the thalassemic sera might contain
      factors which affect the endothelial cell growth and proliferation by inhibiting
      mitosis in vitro.

PMID- 9640620
TI  - A simple and quantitative method for the determination of tissue factor.
AB  - Tissue factor (TF), a potent initiator of the extrinsic coagulation pathway, is
      believed to have a critical role in thrombogenesis and haemostasis. To elucidate
      the role of TF in the development of various syndrome, we developed a
      quantitative assay method for the determination of TF using FIX complex
      (Profilnine) and the synthetic chromogenic substrate S-2238, all of which are
      commercially available. The method is simple, very sensitive, good linearity and
      applicable to the tissue culture plate, indicating its promising usage for the
      quantitation of TF activity of cells.

PMID- 9640621
TI  - Surface and total tissue factor activity of endothelial cells.
AB  - With a technic that was developed by us, we found that normal human umbilical
      vein endothelial cells (HUVEC) in culture characteristically had very little
      tissue factor (TF) activity either on the surface or in the cells which had been
      disrupted. In the presence of endotoxin (E. coli O26:B6), a trigger for
      thrombosis in septicemic patients, we could not detect an increased TF activity
      of HUVEC on its surface. However, an increase in TF (total TF) was detected after
      disruption of the cells. The increase in total TF was dose-dependent. Endotoxin
      at the concentration of 10 micrograms/ml caused around 5 fold increase in total
      TF activity compared to that of HUVEC in the absence of endotoxin.

PMID- 9640622
TI  - A double-blind placebo control trial of dilazep in beta-thalassemia/hemoglobin E
      patients.
AB  - Since the obtained results from the pilot study indicated that dilazep which was
      a membrane stabilizer would be benefit to treatment and prevention of anemia and
      chronic leg ulcer in beta-thalassemia/hemoglobin E (beta-thal/HbE) patients, the
      authors had continued the study in a second phase, ie a double blind placebo
      control trial. Twenty-seven beta-thal/HbE patients were recruited in the study.
      Eight patients who suffered from chronic leg ulcer were given dilazep. The rest
      of patients were given dilazep or placebo according to a randomized table. Hence,
      16 patients received dilazep and 11 received placebo. When we compared the number
      of unit of blood transfusion, hemoglobin level, 2-3 DPG and P50 value between the
      dilazep and placebo groups using unpaired t-test, we found that there were no
      statistical differences in any of the parameters. However, when we compared the
      data within the group using paired t-test, there was statistical decrease in
      blood requirement after treatment in the dilazep group (p < 0.05). Concerning
      with the treatment of chronic leg ulcer, 3 in 8 patients were completely healed
      within 3 months, 4 in 8 patients were improved and 1 in 8 patients was not
      improved. There were complaints of skin itching and mild epigastric pain in
      placebo group but the liver function tests, kidney function tests and cardiac
      enzyme did not significantly change during the medication.

PMID- 9640623
TI  - Risk factors for chronic rejection--a clinical perspective.

PMID- 9640624
TI  - Removal of primate xenoreactive natural antibodies by extracorporeal perfusion of
      pig kidneys and livers.
AB  - Organ perfusion is one of the possible strategies to attenuate rejection of
      discordant xenografts by reducing the levels of the recipient's xenoreactive
      natural antibodies (XNA). Its efficacy in terms of XNA removal was studied in
      models of primate blood or plasma perfusion through porcine kidneys or livers,
      with special attention to haematological consequences and potential side-effects.
      We first perfused the blood of rhesus monkeys through pig kidneys and livers, and
      demonstrated that the perfusion of a pig liver resulted in higher XNA adsorption
      (72 +/- 13%) than the perfusion of a pig kidney (51 +/- 25%). However, when we
      normalized for the weight of the perfused organs and for levels of natural
      antibodies in individual monkeys, livers adsorbed less antibody (1.4 +/- 0.9 U
      antibody/g) than kidneys (7.2 +/- 7 U antibody/g). Histological signs of
      rejection were observed in perfused kidneys, but not in perfused livers. A major
      drawback of the perfusion of blood through livers was a considerable decrease in
      the primates' haemoglobin and platelet levels. To avoid this, we developed a
      plasma liver perfusion device. This method allowed a significant improvement in
      the haemodynamic state of primates and was particularly effective in preventing
      anaemia. Moreover, plasma liver perfusion was as effective as blood liver
      perfusion to remove natural antibodies and, resulted in a marked decrease in
      their functional activity as assessed by complement-dependent cytotoxicity (CDC)
      and antibody-dependent cell-mediated cytotoxicity (ADCC). The level of other
      plasma proteins was not significantly affected, apart from a dilution effect.
      After xenoperfusion a strong antibody response was evidenced by ELISA, CDC and
      ADCC between days 7 and 14 and then decreased progressively. We conclude that the
      separation of blood to allow the perfusion of plasma through a pig organ is safer
      than the perfusion of unseparated blood and is associated with efficient natural
      antibody removal. However, organ perfusion is limited by a rebound in antibody
      levels after a few days, and thus will have to be associated with anti-B cell
      immunosuppressive therapy for long-term or repeated applications.

PMID- 9640625
TI  - Mycophenolate mofetil reduces production of interferon-dependent major
      histocompatibility complex induction during allograft rejection, probably by
      limiting clonal expansion.
AB  - The immunosuppressive drug mycophenolate mofetil (MMF) acts by releasing
      mycophenolic acid (MPA), which inhibits the enzyme inosine monophosphate
      dehydrogenase (IMPDH) and thus inhibits de novo purine synthesis. Unlike
      cyclosporine (CsA), MMF has no direct effect on cytokine gene expression in
      vitro. We examined the effect of MMF, in comparison to CsA, on in vivo production
      of interferon-gamma (IFN-gamma) in mice. Two stimuli for IFN-gamma induction were
      used: (1) allogeneic P815 mastocytoma ascites tumour cells and (2) bacterial
      lipopolysaccharide (LPS). The allogeneic response is dependent on clonal
      expansion of T cells, while the LPS response is polyclonal and T cell
      independent. Since major histocompatibility complex (MHC) induction in mouse
      kidney is IFN-gamma dependent, we assessed the in vivo induction of IFN-gamma
      indirectly by measuring MHC induction in mouse kidneys in three systems:
      radiolabelled antibody binding assay, immunoperoxidase staining in tissue
      sections, and Northern blotting for steady-state MHC mRNA levels. IFN-gamma
      steady-state mRNA levels were assessed by reverse transcriptase polymerase chain
      reaction (RT-PCR). In the allogeneic response, MMF (40-160 mg/kg/day) reduced the
      production of IFN-gamma in a dose-dependent fashion. MHC class I and II induction
      was reduced by 35% to 74% and 30% to 74%, respectively. However, MMF had less
      effect on the induction of MHC by a nonimmune stimulus, bacterial LPS, whereas
      CsA reduced the induction of IFN-gamma in both responses. We conclude that MMF
      reduces the IFN-dependent induction of MHC in vivo during specific immune
      responses, probably by limiting clonal expansion, while preserving nonspecific
      cytokine production in response to LPS.

PMID- 9640626
TI  - Mutual tolerance after liver and not after heart transplantation? Evaluation of
      patient-anti-donor and donor-anti-patient responses by mixed lymphocyte culture.
AB  - The ultimate goal in organ transplantation is the induction of donor-specific
      transplantation tolerance. The fact that in some patients it is possible to
      withdraw immunosuppressive therapy completely, suggests that immunological
      adaptation or donor-specific nonresponsiveness can occur following
      transplantation. In earlier studies we have shown that after blood transfusion,
      the mixed lymphocyte reactivity of the donor against patient peripheral blood
      mononuclear lymphocytes taken after blood transfusion gradually decreased with
      time. This may reflect the induction of an immunoregulatory mechanism, which
      protects the recipient against an immune reaction of the donor, enhancing a state
      of mixed chimerism. A similar phenomenon might also play a role in the
      immunological mechanism leading to transplantation tolerance. Therefore, we
      studied responses in patients with a well-functioning liver and heart transplant
      using a primed lymphocyte test (PLT) and a mixed lymphocyte culture (MLC). Two
      years after liver transplantation the PLT and MLC responses of patient against
      donor were decreased significantly compared to the situation before
      transplantation. The response of donor against patient was also lower two years
      after transplantation. The decreased responses were donor-specific since
      responses to third-party cells generally remained unchanged. In heart transplant
      recipients we could not detect a donor-specific downregulation. The reversed
      response, of donor against patient, was not different from responses of third
      party against patient cells. Therefore, we conclude that donor-specific
      nonresponsiveness is not induced in patients with well-functioning heart
      transplants. In contrast, after a successful liver transplantation the response
      of patient against donor is decreased, as is the reversed response. It may be
      valuable to test whether in liver transplant patients withdrawing or reducing of
      maintenance immunosuppression is permitted for patients who appear to have
      developed two-way donor-specific hyporeactivity.

PMID- 9640627
TI  - Pattern of cytokine expression in circulation CD57+ T cells from long-term renal
      allograft recipients.
AB  - We made a quantitative analysis of the lymphokine mRNA and of proteins produced
      by CD57+ and CD57- circulating T cells isolated from long-term kidney
      transplanted patients with expanded CD4+/CD57+ and CD8+/CD57+ T cells, and from
      normal individuals. We concentrated on IL-2 and IFN-gamma, which define a Th1
      like type of lymphokine production, and on IL-4 which defines a Th-2-like type.
      We also analysed the production of IL-10 which is endowed with inhibitory effects
      on IL-2 and IFN-gamma synthesis, and of TNF-alpha, a pleiotropic inflammatory
      cytokine. On ionomycin + PMA stimulation, which reveals the intrinsic potential
      of lymphokine production by T cells, the CD57+ T cell subsets from all
      individuals produced high amounts of IFN-gamma and TNF-alpha mRNA and protein.
      They also produced IL-2, but to a much lesser extend than their CD57-
      counterparts, and little IL-4 and IL-10. They were no more capable of producing
      IL-2 when stimulated through the CD3/TCR in the presence of monocytes, yet still
      synthesized IFN-gamma. Our data suggest that the in vivo expansion of CD57+ T
      cells in stable allograft renal recipients might correspond to Th1 energized
      cells which on triggering of cell surface receptors hardly secrete lymphokines
      involved in cell cycle progression, but can still exert some effector functions,
      including IFN-gamma secretion.

PMID- 9640628
TI  - Effect of leflunomide and cyclosporine on graft survival and changes in
      lymphocyte phenotypes in a rat heart allotransplantation model.
AB  - Cyclosporine-A (CSA) and leflunomide (LF) can delay or prevent organ graft
      rejection. We investigated the combination of LF, CSA and splenectomy on graft
      survival and changes in lymphocyte phenotypes (LP) in a rat allotransplantation
      model. In the study 19 Lewis rats were splenectomized prior to heterotopic heart
      transplantation. SPRD rats served as donors. The recipients were divided into
      three groups: A--five animals received CSA and LF for two weeks, B--five received
      intermittent CSA and LF for the whole investigation period and C--nine received
      no drug therapy. LP was quantified relatively by flow cytometric analysis. We
      found that graft survival was longer in group A (median 155 days, range 52-348)
      and B (341, range 338-342), compared to group C (8, range 7-13). The histological
      examination, however, revealed signs of rejection in all allografts. In group A
      all except one animal and in group C the morphological changes were characterized
      by severe acute rejection. In contrast, one animal in group A and all the animals
      in group B revealed signs of moderate acute rejection and in most animals signs
      of chronic rejection were also found. The reduction of Pan-T and CD4+ cells in
      group B compared to the control group was associated with no clinical rejection,
      while the increase of CD8+ cells in group C and partly in group A (except for
      animal 3) was associated with clinical rejection. No difference in LP was
      detected between groups A and B in the study period. We concluded that a
      combination of CSA, LF and splenectomy was efficient in preventing clinical
      rejection, however, there were signs of rejection morphologically even in animals
      without clinical rejection. The changes in LP over time could not predict the
      clinical outcome. However, increase in CD8+ cells was highly associated to
      clinical rejection among nonimmunosuppresed animals.

PMID- 9640629
TI  - The effect of anti-CD3-immunotoxin on T lymphocyte function in vitro.
AB  - Recent advances in the design of immunotoxins (IT) have yielded significant
      improvements. FN18-CRM9, a construct of anti-CD3 epsilon mAb FN18 and mutated
      diphtheria toxin CRM9 has exhibited high specificity, low systemic toxicity and
      unusual efficacy compared to previous iterations of immunotoxins. Others and we
      have examined this anti-CD3-IT for the purpose of inducing immunological
      tolerance through selective ablation of T cells in rhesus macaques and have
      obtained encouraging results. In order to characterize its mode of action, we
      have examined its effects on peripheral blood and lymph node T cell killing in
      vitro. We have studied the cytotoxic mechanism induced by this anti-CD3-IT as
      well as its effects on proliferation, phenotypic changes and cytokine production
      (IL2, IFN gamma and TNF alpha). The results indicate that anti-CD3-IT was highly
      specific for T cell killing at doses as low as 1 x 10(6) micrograms/ml and showed
      a maximal effect at 48 h after exposure. The toxicity was restricted to T cells,
      as B cells and other bystander cells were spared. This immunotoxin was shown to
      induce T cell apoptosis, as assessed by TUNEL assay, DNA content and
      cytotoxicity. Fas expression was upregulated on T cells within 24 h after in
      vitro exposure to anti-CD3-IT, suggesting an early T cell activation phase prior
      to T cell death. T cell killing was manifest as an early cell cycle arrest at the
      G1/S phase transition, which appeared to virtually eliminate the production of
      cytokines. These findings corroborate the temporal, specificity and quantitative
      patterns for anti-CD3 immunotoxin administration previously observed in vivo.

PMID- 9640630
TI  - Antigen presenting cells and chimerism.

PMID- 9640631
TI  - Women's drug use and HIV risk: findings from NIDA's Cooperative Agreement for
      Community-Based Outreach/Intervention Research Program.

PMID- 9640632
TI  - Women drug users and HIV prevention: overview of findings and research needs.

PMID- 9640633
TI  - HIV sex and drug risk behavior and behavior change in a national sample of
      injection drug and crack cocaine using women.
AB  - This paper describes HIV sex and drug risk behavior and behavior change of
      injection drug and crack cocaine using women enrolled in a national multi-site
      Cooperative Agreement program. Baseline data on the 1,403 women who were randomly
      assigned to a two session intervention that was standardized across sites
      indicate that sex and drug risk behavior for becoming infected with HIV was
      considerable. Six-month post intervention follow-up data for the same sample of
      women show that significant reductions in sex and drug risk behavior were
      observed for the entire sample of women for the risk variables under study.
      Significant reductions were also demonstrated for various sub-groups of women
      enrolled in the study on most of the sex and drug risk variables. Given these
      findings, it appears that the standard intervention was effective in assisting
      drug using women reduce their behaviors that put them at risk of becoming
      infected with HIV. Further research in needed on the development and evaluation
      of HIV interventions that target specific risk behaviors and various HIV risk
      behavior profiles of women.

PMID- 9640634
TI  - Effectiveness of HIV interventions among women drug users.
AB  - A prospective cohort study was conducted among chronic injecting and crack
      cocaine drug using women. The hypothesis tested was that participation in a
      standard-plus-innovative intervention was more likely to produce behavior change
      than participation in a standard intervention. Standardized intervention
      protocols and corresponding instruments were designed. Data were collected on
      drug and sex risk behaviors at baseline and six-month follow-up intervals. The
      level of behavioral change in two intervention arms--standard and a standard-plus
      innovative intervention--was measured by composite sex risk and drug risk scores
      using the generalized estimating equation approach. The results show that on four
      risk measures the enhanced intervention was significantly associated with
      positive change in both drug use and sexual behavior: less frequent drug use,
      less drug use during sex, and more frequent condom use during particular
      frequencies for specific types of sexual activities. Public health interventions
      are effective when targeting specific risk behaviors through interventions
      tailored to prevent HIV and reduce risk behaviors among specific cultural and
      gender groups.

PMID- 9640635
TI  - AIDS risk perception among women drug users in Hartford, CT.
AB  - This paper reports the findings of a study of congruence between AIDS risk
      perception and risk behavior in a sample of outreach-recruited out-of-treatment
      injection and non-injection crack cocaine using women in Hartford, CT. While
      rates of drug- and sex-related AIDS risk were high in this sample, perception of
      risk was low among many of the respondents. Variation in risk perception reflects
      sociodemographic differences in the sample, with those women who were most
      socially isolated exhibiting the greatest incongruence between personal risk and
      risk perception. Women who have had contact with health or social service
      programs were the most likely to report reductions in risk behavior.

PMID- 9640636
TI  - Sex partners of Alaskan drug users: HIV transmission between white men and Alaska
      Native women.
AB  - This study describes patterns of sexual behavior and condom use in a sample of
      1125 Black, White, and Alaska Native drug users. Data are self-reports of recent
      sexual behavior, including descriptions of (up to) the five most recent sex
      partners. This provided information on 1116 sex partner pairs, of which at least
      one partner was a drug user. Sex partner pairs involving a White man and an
      Alaska Native woman were frequently reported. Level of condom use within these
      pairs was significantly lower than within all other pairs. The implications of a
      potential vector of HIV transmission from White, drug using men to Alaska Native
      women are discussed.

PMID- 9640637
TI  - A comparison of HIV risk behaviors among women drug users from two cities in a
      rural state: recommendations for targeted prevention.
AB  - Most HIV prevention programs for women target individual risk behaviors while the
      influence of larger contextual factors, such as city of residence, are often
      neglected. This preliminary study compares women drug users from two different
      cities in the largely rural state of Kentucky on HIV risk behaviors. The women
      are from Lexington, a medium sized metropolitan area, and from Louisville, a
      large metropolitan area. Comparisons between the women from the two cities
      indicate that there are many similarities in their risk behaviors, but also some
      important differences. The women from Lexington (the smaller city), are more
      likely to be at risk for becoming infected with HIV due to their drug use, while
      the women from Louisville (the larger city) are more likely to be at risk because
      of their sex exchange practices and economic situation. The implications for
      prevention are discussed.

PMID- 9640638
TI  - Social influences: living arrangements of drug using women at risk for HIV
      infection.
AB  - The purpose of this study was to explore the associations among living
      arrangements, HIV seroprevalence, and HIV risk and protective factors among 1,322
      drug users participating in the University of Miami CARES (Community AIDS
      Research and Evaluation Studies) HIV intervention program. Living arrangements
      may be associated with HIV prevention behaviors; however, these influences can be
      either protective or destructive and therefore merit further examination.
      Statistical analyses indicated differences in the living arrangements of women
      compared with men, and significant associations were noted among women's living
      arrangements, HIV seroprevalence, risk behaviors and protective behaviors. The
      data from this study suggest that future HIV prevention research should
      investigate not only high-risk individuals, but persons with whom they interact
      often, especially those with whom they live or with whom they have sex. The next
      phase of HIV and drug interventions should be attentive to the incorporation of
      social context and social influences, paying particular attention to understudied
      populations such as high-risk women.

PMID- 9640639
TI  - Differences in condom behaviors and beliefs among female drug users recruited
      from two cities.
AB  - This paper examines predictors of condom cognitions and condom use for vaginal
      sex within women's main and paying partnerships. The sample consisted of active
      injection drug and crack-using women recruited from two cities with disparate HIV
      rates. A total of 338 drug-using women who reported vaginal sex with a main
      and/or paying partner in the prior 30 days were recruited for this study.
      Recruitment site was a significant predictor for several of the variables
      examined, for both main and paying partners. Ethnicity and prior HIV test result
      were also significant predictors, but only for main sex partners. Findings
      support previous research and suggest that the factors which predict condom
      beliefs, intention, and behaviors are different for main versus paying partners.
      Interventions designed to increase condom use must recognize that cognitive
      factors associated with condom use may vary by partner type, ethnicity, and
      recruitment site, particularly when important contextual variables, such as local
      seroprevalence, vary.

PMID- 9640640
TI  - Violence and HIV sexual risk behaviors among female sex partners of male drug
      users.
AB  - OBJECTIVE: Violence and HIV are emerging as interconnected public health hazards
      among drug users and their families. The purposes of this study are to (1)
      determine the prevalence of sexual and physical abuse of non-drug-using female
      sex partners of male drug users, and (2) ascertain the association between such
      violence and HIV-related risk behaviors. METHODS: From 11/93 to 11/95, 208 female
      sex partners of injection drug or crack users in Collier County, FL, Tucson, AZ,
      and Portland, OR, were interviewed as part of a NIDA-funded HIV risk reduction
      project. Their mean age was 30 years (range 18-54); 21% were White, 6% African
      American, 7% Native American, and 63% Hispanic. RESULTS: Of the 208 women, 28%
      reported being sexually molested and 20% raped before age 13; 41% reported being
      raped at least once in their lifetime. Forty-two percent of the women were
      physically assaulted by their sex partners; 36% had been threatened with
      assaulted by their sex partners. Those who were raped or threatened with assault
      were more likely to have multiple sex partners and engage in unprotected anal
      sex; there was a trend for women who had been physically assaulted to be more
      likely to engage in unprotected anal sex. DISCUSSION: Rape, assault and the
      threat of assault are commonplace in the histories of female sex partners of male
      drug users. Experiences of violence and threats of violence are associated with
      heightened risk for the sexual transmission of HIV. Providers of HIV prevention
      need to understand the sequelae of violence, and design interventions which
      empower women to protect themselves from sexual transmission of HIV.

PMID- 9640641
TI  - Urban crack users: gender differences in drug use, HIV risk and health status.
AB  - This study assessed gender differences in drug use, HIV risk, and health status
      in a sample of urban crack users. Using targeted sampling, 1434 crack users (66%
      male and primarily African-American and Puerto Rican), were recruited from the
      streets of East Harlem, New York City. A standardized, structured interview was
      administered, drug use was validated by urinalysis, and HIV testing was offered.
      Gender differences were observed on sociodemographic variables and patterns of
      drug use. Other than welfare, men and women cited different major sources of
      income. Women reported greater use of crack, and men were more likely to use
      injection drugs as well as crack. Data on sexual risk indicated that women had
      more sexual partners than men, but the percentage of unprotected vaginal sex for
      both men and women was greater for those who did not exchange sex for drugs
      and/or money. The number of persons already infected with HIV was substantial.
      Many reported histories of other sexually transmitted diseases which were
      generally higher among men. Future research should investigate the relationship
      between gender and other factors (e.g., ethnicity, geographic location)
      associated with HIV risk.

PMID- 9640642
TI  - Predictors of HIV infection among women drug users in New York and Miami.
AB  - In the US, the number of women diagnosed with AIDS continues to increase. In this
      study, women in New York City (East Harlem) and Miami, two sites with high rates
      of drug use and HIV infection, were first compared on sociodemographic variables
      and risk behaviors. Logistic regression analyses were used to identify
      significant, independent predictors of HIV infection in each city. In comparing
      women from the two cities, several differences in sociodemographic
      characteristics and drug use were observed. In both cities, ever exchanging sex
      for drugs and/or money was predictive of HIV infection; and in East Harlem only,
      other lifetime risk variables independently predicted HIV infection: drug
      injection, having a sexually transmitted disease, and not having graduated from
      high school. Results suggest that intervention efforts with women who exchange
      sex should be intensified in both cities. Also, further comparisons of women drug
      users in AIDS epicenter cities are necessary to provide information on
      similarities and differences in sociodemographic characteristics and individual
      risk behaviors. More research attention should be focused on examining the social
      context of HIV risk in order to develop innovative intervention strategies which
      focus on the link between contextual factors and HIV infection.

PMID- 9640643
TI  - Streets, drugs, and the economy of sex in the age of AIDS.
AB  - Drug addicted women whose economic and social base is urban streets face limited
      options for income generation and multiple dangers of predation, assault, arrest,
      and illness. Exchanging sex for money or drugs offers one important source of
      income in this context. Yet the legal, social, and safety risks associated with
      these exchanges reduce the likelihood of regular safer sex practices during these
      encounters, thereby increasing the risk of HIV infection. Such conditions lead
      women engaged in sexual exchanges for money to varied and complex responses
      influenced by multiple and often contradictory pressures, both personal and
      contextual. Street-recruited women drug users in an AIDS prevention program in
      Hart-ford, Connecticut reported a range of condom use when engaging in sex for
      money exchanges. This paper explores their differences by ethnicity, economic
      resources, and drug use, and analyzes these and other factors that impact on
      street risks through sexual income generation. Surveys and in-depth interviews
      with drug-addicted women sex workers describe their various approaches to
      addressing multiple risks on the streets and suggest significant effort by women
      in these contexts to avoid the many risks, including HIV infection.

PMID- 9640644
TI  - ATP-binding-cassette (ABC) transport systems: functional and structural aspects
      of the ATP-hydrolyzing subunits/domains.
AB  - Members of the superfamily of adenosine triphosphate (ATP)-binding-cassette (ABC)
      transport systems couple the hydrolysis of ATP to the translocation of solutes
      across a biological membrane. Recognized by their common modular organization and
      two sequence motifs that constitute a nucleotide binding fold, ABC transporters
      are widespread among all living organisms. They accomplish not only the uptake of
      nutrients in bacteria but are involved in diverse processes, such as signal
      transduction, protein secretion, drug and antibiotic resistance, antigen
      presentation, bacterial pathogenesis and sporulation. Moreover, some human
      inheritable diseases, like cystic fibrosis, adrenoleukodystrophy and Stargardt's
      disease are caused by defective ABC transport systems. Thus, albeit of major
      significance, details of the molecular mechanism by which these systems exert
      their functions are still poorly understood. In this review, recent data
      concerning the properties and putative role of the ATP-hydrolyzing
      subunits/domains are summarized and compared between bacterial and eukaryotic
      systems.

PMID- 9640645
TI  - Physiology of organic nitrogen acquisition by ectomycorrhizal fungi and
      ectomycorrhizas.
AB  - Ectomycorrhizal fungi are symbiotically associated microorganisms which
      ecological importance has been repeatedly demonstrated. There has been a
      considerable amount of research aimed at assessing the ability of ectomycorrhizal
      fungi and ectomycorrhizas to utilize organic nitrogen sources. The fate of soil
      proteins, peptides and amino acids has been studied from a number of
      perspectives. Exocellular hydrolytic enzymes have been detected and characterized
      in a number of ectomycorrhizal and ericoid fungi. Studies on amino acid transport
      through the plasma membrane have demonstrated the ability of ectomycorrhizal
      fungi to take up the products of proteolytic activities. Investigations on
      intracellular metabolism of amino acids have allowed the identification of the
      metabolic pathways involved. Possible intracellular compartmentation of amino
      acids will be examined by immunocytochemistry. Further translocation of amino
      acids in symbiotic tissues has been established by experiments using isotopic
      tracers, although the exact nature of the nitrogenous compounds transferred at
      the symbiotic interface remained unclear. One of the main future challenges in
      the physiology of organic nitrogen acquisition is to determine the nature, the
      regulation and the location of N-compound transporters at the soil-fungus and
      fungus-plant interfaces. The molecular approach which is just emerging in this
      particular research area will greatly improve our knowledge. Future research
      should also address the extent of competition between different ectomycorrhizal
      species and between different microbial populations for organic nitrogen.

PMID- 9640646
TI  - Adhesin-receptor interactions in Pasteurellaceae.
AB  - The ability of bacteria to adhere to mucosal epithelium is dependent on the
      expression of adhesive molecules or structures, called adhesins, that allow
      attachment of the organisms to complementary molecules on mucosal surfaces, the
      receptors. Important human and animal pathogens are found among the
      Pasteurellaceae family which includes Haemophilus, Actinobacillus, and
      Pasteurella organisms. The purpose of this paper is to review the adhesin
      receptor systems found in Pasteurellaceae, with an emphasis on recent
      developments in this specific area. Most of these organisms can employ multiple
      molecular mechanisms of adherence (or multiple adhesins) to initiate infection.
      Indeed, a wide variety of adhesins are expressed by members of the
      Pasteurellaceae, and different proteins (e.g. fimbriae, fibrils, outer membrane
      proteins) as well as polysaccharides (lipooligosaccharides, lipopolysaccharides,
      capsular polysaccharides) were clearly shown to play an important role in
      adherence. In many instances, these adhesins have proved to represent good
      vaccine candidates. Surprisingly, the receptors on host mucosal surfaces have yet
      been identified in very few cases.

PMID- 9640647
TI  - Habitat islands, genetic diversity, and gene flow in a Patagonian rodent.
AB  - The effects of terrestrial habitat islands on gene flow and genetic diversity in
      animal populations have been predicted and discussed in theoretical terms, but
      empirical data are needed to test these predictions and provide an understanding
      of the relationships of life-history characteristics to genetics of insular
      species. We studied saxicolous mice (Phyllotis xanthopygus) in Patagonia to
      explore genetic structure, phylogeography, and gene flow in a species inhabiting
      natural habitat islands. Phylogeographic analyses based on mtDNA sequences
      revealed two haplotype clades, which presumably reflect early Pleistocene factors
      that temporarily separated the mice into two geographically isolated groups. The
      Rio Chubut, which lies within a glacial drainage basin bisecting northern
      Patagonia, might have affected gene flow in the species. Although we anticipated
      isolation by distance and founder phenomena associated with habitat islands, in
      some habitat patches we found evidence of high local genetic diversity. The
      amount of divergence in the mitochondrial cytochrome b gene (approximately 3.4%)
      in animals at a single locality could best be explained through a combination of
      historical factors and metapopulation source-sink theory. Demographic shifts,
      dispersal, and episodic recolonization are important in the life history and
      genetic population structure of P. xanthopygus.

PMID- 9640648
TI  - Molecular population genetics of the red kangaroo (Macropus rufus): mtDNA
      variation.
AB  - The genetic population structure of a large, wide-ranging marsupial, the red
      kangaroo (Macropus rufus) was assessed using sequence and haplotype frequency
      data of mitochondrial DNA (mtDNA) from locations across the species range in
      Australia. Results from sequence data revealed extensive haplotype diversity
      within the red kangaroo (32/34 sequences were unique). Sequence diversity was
      distributed within rather than between geographical regions across the species
      range. Genetic connectivity across the range of the species has therefore been
      maintained over the long term. On a smaller within-region scale, significant
      genetic structuring was evident from heterogeneity of haplotype frequencies
      amongst sampling sites. The geographical scale of panmictic populations differed
      across the continent with more restricted genetic populations occurring in areas
      with greater topographic and habitat complexity. We propose that these
      differences in area of genetic populations are the result of population responses
      to limiting ecological factors during drought.

PMID- 9640649
TI  - Molecular genetic identification of southern hemisphere beaked whales (Cetacea:
      Ziphiidae).
AB  - To assist in the species-level identification of stranded and hunted beaked
      whales, we compiled a database of 'reference' sequences from the mitochondrial
      DNA control region for 15 of the 20 described ziphiid species. Reference samples
      for eight species were obtained from stranded animals in New Zealand and South
      Australia. Sequences for a further seven species were obtained from a previously
      published report. This database was used to identify 20 'test' samples obtained
      from incompletely documented strandings around New Zealand. Analyses showed that
      four of these 'test' specimens (20%) had initially been misidentified. These
      included two animals of particular interest: (i) a Blainville's beaked whale
      (Mesoplodon densirostris), the first record of this species in New Zealand
      waters; and, (ii) a juvenile Andrews' beaked whale (Mesoplodon bowdoini), a
      species known from just over 20 strandings worldwide. A published sequence from a
      beaked whale product purchased in the Republic of Korea was identified as a
      Cuvier's beaked whale (Ziphius cavirostris). Levels of intra- and interspecific
      variation were compared to determine the potential for misidentification when the
      database or taxonomy is incomplete. Intraspecific variation was generally < 2%,
      and interspecific divergence was generally > 4.7%. Exceptions were within-species
      variation in Hyperoodon planifrons, southern bottlenosed whale (4.12%), which
      exceeded the variation between the two species of Berardius (3.78%), and
      variation between the two specimens assigned to M. hectori, Hector's beaked whale
      (7.14%). The latter case appears to be an error in species identification, and
      could represent the discovery of a new species of beaked whale.

PMID- 9640650
TI  - Population structure of nuclear and mitochondrial DNA variation among humpback
      whales in the North Pacific.
AB  - The population structure of variation in a nuclear actin intron and the control
      region of mitochondrial DNA is described for humpback whales from eight regions
      in the North Pacific Ocean: central California, Baja Peninsula, nearshore Mexico
      (Bahia Banderas), offshore Mexico (Socorro Island), southeastern Alaska, central
      Alaska (Prince Williams Sound), Hawaii and Japan (Ogasawara Islands). Primary
      mtDNA haplotypes and intron alleles were identified using selected restriction
      fragment length polymorphisms of target sequences amplified by the polymerase
      chain reaction (PCR-RFLP). There was little evidence of heterogeneity in the
      frequencies of mtDNA haplotypes or actin intron alleles due to the year or sex
      composition of the sample. However, frequencies of four mtDNA haplotypes showed
      marked regional differences in their distributions (phi ST = 0.277; P < 0.001; n
      = 205 individuals) while the two alleles showed significant, but less marked,
      regional differences (phi ST = 0.033; P < 0.013; n = 400 chromosomes). An
      hierarchical analysis of variance in frequencies of haplotypes and alleles
      supported the grouping of six regions into a central and eastern stock with
      further partitioning of variance among regions within stocks for haplotypes but
      not for alleles. Based on available genetic and demographic evidence, the
      southeastern Alaska and central California feeding grounds were selected for
      additional analyses of nuclear differentiation using allelic variation at four
      microsatellite loci. All four loci showed significant differences in allele
      frequencies (overall FST = 0.043; P < 0.001; average n = 139 chromosomes per
      locus), indicating at least partial reproductive isolation between the two
      regions as well as the segregation of mtDNA lineages. Although the two feeding
      grounds were not panmictic for nuclear or mitochondrial loci, estimates of long
      term migration rates suggested that male-mediated gene flow was several-fold
      greater than female gene flow. These results include and extend the range and
      sample size of previously published work, providing additional evidence for the
      significance of genetic management units within oceanic populations of humpback
      whales.

PMID- 9640654
TI  - Microsatellite loci for stringless bees.

PMID- 9640655
TI  - Characterization of coastal cutthroat trout (Oncorhynchus clarki clarki)
      microsatellites and their conservation in other salmonids.

PMID- 9640656
TI  - Broader context, global outlook.

PMID- 9640657
TI  - Sending a message.

PMID- 9640658
TI  - Steeling ourselves against cardiac arrest.

PMID- 9640659
TI  - Have you heard?

PMID- 9640660
TI  - Effects of (+)-8',8',8'-trifluoroabscisic acid on alpha-amylase expression and
      sugar accumulation in rice cells.
AB  - The effects of (+)-8',8',8'-trifluoroabscisic acid (trifluoro-ABA) on alpha
      amylase expression were studied in rice embryoless half-seeds, scutella, and
      suspension-cultured cells derived from the embryo, and the effects of the analog
      on sugar accumulation were also studied in scutella and suspension-cultured
      cells. Treatment with (+)-trifluoro-ABA strongly inhibited the gibberellic acid
      inducible expression of alpha-amylase I-1 encoded by RAmy1A in the aleurone
      layers of embryoless half-seeds at the levels of transcription, protein
      synthesis, and enzyme activity. It was also found that (+)-trifluoro-ABA
      stimulated (i) the uptake of glucose from the incubation medium and (ii) the
      synthesis of sucrose in scutellar tissues and suspension-cultured cells of rice.
      The biological activity of (+)-trifluoro-ABA was found to be more potent and
      persistent than that of natural ABA. We further examined the effects of trifluoro
      ABA on the expression of alpha-amylase I-1 in scutellar tissues and suspension
      cultured cells. It was found that (+)-trifluoro-ABA did not inhibit the formation
      of alpha-amylase I-1 in the absence of external glucose. However, glucose and (+)
      trifluoro-ABA cooperatively suppressed the formation of alpha-amylase I-1.
      Judging from these results, we conclude that the regulatory mechanism for the
      expression of alpha-amylase I-1 in the scutellar epithelium is distinguishable
      from that operating in the aleurone layer.

PMID- 9640661
TI  - In rice, Oryzalin and abscisic acid differentially affect tubulin mRNA and
      protein levels.
AB  - The effect of the anti-microtubular drug Oryzalin (3,5-dinitro-N4,N4
      dipropylsulfanilamide) on growth and elongation of rice (Oryza sativa L. cv.
      Arborio) roots and coleoptiles was investigated. At 100 nM, Oryzalin strongly
      reduced primary root elongation, caused loss of cell anisotropy and the
      disappearance of the cortical microtubule array. Under these conditions the
      amounts of alpha- and beta-tubulin protein, but not mRNA, were heavily reduced.
      Similar data were also obtained in coleoptile segments treated with different
      concentrations of Oryzalin. However, when coleoptile elongation was inhibited by
      cis-abscisic acid, remarkable decreases in alpha- and beta-tubulin accumulation
      were observed to occur at the mRNA level but not at the protein level. The
      transcriptional decreases could be reversed by re-addition of 3-indole acetic
      acid. Altogether, these data indicate that rice tubulin accumulation can be
      controlled at different levels, mRNA or protein, in response to Oryzalin or
      abscisic acid treatments.

PMID- 9640662
TI  - Gravitropism and gravimorphism during regeneration from protoplasts of the moss
      Ceratodon purpureus (Hedw.) Brid.
AB  - Wild-type (WT) protonemata of the moss Ceratodon purpureus grow upwards in
      darkness (negative gravitropism), whereas protonemata of the mutant, wrong-way
      response (wwr-1) grow down. Since Ceratodon protoplasts regenerate to form new
      protonemata, we analyzed whether the direction of filament emergence was
      influenced by gravity (gravimorphism) and determined the cytological events that
      correlated with the onset of gravitropism in WT and wwr-1 filaments formed de
      novo. In the WT the direction of filament emergence appeared to be gravimorphic
      as more than 66% of the new filaments emerged above the horizontal. In contrast,
      the direction of filament emergence was random in wwr-1. Tip-growing cells of
      both genotypes became gravitropic within a total of one to two cell divisions.
      Gravitropic curvature in wwr-1 was opposite in direction to that of WT, and the
      timing of curvature was comparable, indicating that the wwr-1 mutation acts
      during the onset of gravitropic competence. In time-lapse studies of both
      genotypes, neither a plastid-free zone nor obvious and extensive plastid
      sedimentation characteristic of mature dark-grown protonemata was observed in the
      new filaments prior to gravitropic curvature. Thus, it appears that these latter
      two features are not required for gravitropism in new protonemal filaments from
      protoplasts.

PMID- 9640663
TI  - Purification of ornithine carbamoyltransferase from kidney bean (Phaseolus
      vulgaris L.) leaves and comparison of the properties of the enzyme from
      canavanine-containing and -deficient plants.
AB  - Kidney bean (Phaseolus vulgaris L.) ornithine carbamoyltransferase (OCT; EC
      2.1.3.3) was purified to homogeneity from leaf homogenates in a single-step
      procedure, using delta-N-(phosphonoacetyl)-L-ornithine-Sepharose 6B affinity
      chromatography. The 8540-fold-purified OCT exhibited a specific activity of 526
      micromoles citrulline per minute per milligram of protein at 35 degrees C and pH
      8.0. The enzyme represents approximately 0.01% of the total soluble protein in
      the leaf. The molecular mass of the native enzyme was approximately 109 kDa as
      estimated by Sephacryl S-200 gel filtration chromatography. The purified protein
      ran as a single band of molecular mass 36 kDa when subjected to sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis and at a single isoelectric point of
      6.6 when subjected to denaturing isoelectric focusing. These results suggest that
      the enzyme is a trimer of identical subunits. Among the tested amino acids, L
      cysteine and S-carbamoyl-L-cysteine were the most effective inhibitors of the
      enzyme. The OCT of kidney bean showed a very low activity towards canaline. The
      OCTs of canavanine-deficient plants have very low canaline-dependent activities,
      but the OCTs of canavanine-containing plants showed high canaline-dependent
      activities. It was assumed that the substrate specificity of this enzyme
      determines the canavanine synthetic activity of the urea cycle.

PMID- 9640664
TI  - Membrane fractionation and enrichment of callose synthase from pollen tubes of
      Nicotiana alata Link et Otto.
AB  - The callose synthase (UDP-glucose: 1,3-beta-D-glucan 3-beta-D-glucosyl
      transferase; EC 2.4.1.34) enzyme (CalS) from pollen tubes of Nicotiana alata Link
      et Otto is responsible for developmentally regulated deposition of the cell wall
      polysaccharide callose. Membrane preparations from N. alata pollen tubes grown in
      liquid culture were fractionated by density-gradient centrifugation. The CalS
      activity sedimented to the denser regions of the gradient, approximately 1.18
      g.ml-1, away from markers for Golgi, endoplasmic reticulum and mitochondria, and
      into fractions enriched in ATPase activity and in membranes staining with
      phosphotungstic acid at low pH. This suggests that pollen-tube CalS is localised
      in the plasma membrane. Callose synthase activity from membranes enriched by
      downward centrifugation was solubilised with digitonin, which gave a 3- to 4-fold
      increase in enzyme activity, and the solubilised activity was then enriched a
      further 10-fold by product entrapment. The complete procedure gave final CalS
      specific activities up to 1000-fold higher than those of pollen-tube homogenates.
      Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that several
      polypeptides co-fractionated with CalS activity through purification, with a
      polypeptide of 190 kDa being enriched in product-entrapment pellets.

PMID- 9640665
TI  - 4-Hydroxybenzoate 3-geranyltransferase from Lithospermum erythrorhizon:
      purification of a plant membrane-bound prenyltransferase.
AB  - Geranyldiphosphate:4-hydroxybenzoate 3-geranyltransferase is a regulatory enzyme
      in the biosynthesis of shikonin, a phytoalexin and pharmaceutical produced by
      cell cultures of Lithospermum erythrorhizon Sieb. et Zucc. In Linsmaier-Skoog
      medium, the activity of this enzyme could be enhanced more than 200-fold by
      addition of methyl jasmonate, and this culture material was used for the
      solubilization and purification of the enzyme. Of various detergents examined,
      digitonin was the most suitable for the solubilization of the enzyme. The
      solubilized enzyme was purified 800-fold by chromatography over diethylaminoethyl
      (DEAE)-Sephacel, Heparin-Sepharose, Reactive Green 19-Agarose, and Cholic Acid
      Agarose. The purified enzyme required magnesium ions as cofactor and was highly
      specific for geranyldiphosphate (GPP) and 4-hydroxybenzoate (4HB) as substrates.
      The K(m) values for 4HB and GPP were calculated by the method of Lineweaver and
      Burk as 18.4 microM and 13.8 microM, respectively.

PMID- 9640666
TI  - Effects of over-expression of strictosidine synthase and tryptophan decarboxylase
      on alkaloid production by cell cultures of Catharanthus roseus.
AB  - Cells of Catharanthus roseus (L.) G. Don were genetically engineered to over
      express the enzymes strictosidine synthase (STR; EC 4.3.3.2) and tryptophan
      decarboxylase (TDC; EC 4.1.1.28), which catalyze key steps in the biosynthesis of
      terpenoid indole alkaloids (TIAs). The cultures established after Agrobacterium
      mediated transformation showed wide phenotypic diversity, reflecting the
      complexity of the biosynthetic pathway. Cultures transgenic for Str consistently
      showed tenfold higher STR activity than wild-type cultures, which favored
      biosynthetic activity through the pathway. Two such lines accumulated over 200
      mg.L-1 of the glucoalkaloid strictosidine and/or strictosidine-derived TIAs,
      including ajmalicine, catharanthine, serpentine, and tabersonine, while
      maintaining wild-type levels of TDC activity. Alkaloid accumulation by highly
      productive transgenic lines showed considerable instability and was strongly
      influenced by culture conditions, such as the hormonal composition of the medium
      and the availability of precursors. High transgene-encoded TDC activity was not
      only unnecessary for increased productivity, but also detrimental to the normal
      growth of the cultures. In contrast, high STR activity was tolerated by the
      cultures and appeared to be necessary, albeit not sufficient, to sustain high
      rates of alkaloid biosynthesis. We conclude that constitutive over-expression of
      Str is highly desirable for increased TIA production. However, given its
      complexity, limited intervention in the TIA pathway will yield positive results
      only in the presence of a favorable epigenetic environment.

PMID- 9640667
TI  - Lysine-rich gamma-zeins are secreted in transgenic Arabidopsis plants.
AB  - We have previously shown that the maize (Zea mays L.) storage prolamine gamma
      zein, accumulates in endoplasmic reticulum-derived protein bodies in transgenic
      plants of Arabidopsis thaliana (L.) ecotype R + P. The retention of gamma-zein in
      the endoplasmic reticulum was found to be mediated by structural features
      contained in the polypeptide, an N-terminal proline-rich and a C-terminal
      cysteine-rich domain which were necessary for the correct retention and assembly
      of gamma-zein within protein bodies (M.I. Geli et al., 1994, Plant Cell 6: 1911
      1922). In the present work we incorporated in the gamma-zein gene lysine-rich
      coding sequences which were positioned after the N-terminal proline-rich domain
      and at five amino-acid residues from the C-terminus. The targeting of lysine-rich
      gamma-zeins was analyzed by expression of chimeric genes regulated by the
      cauliflower mosaic virus (CaMV) 35S promoter in transgenic Arabidopsis plants.
      The lysine-rich gamma-zeins were detected by immunoblotting and we found that
      these proteins were modified posttranslationally to reach their mature form.
      Subcellular fractionation and immunocytochemical studies demonstrated that
      glycosylated lysine-rich gamma-zeins were secreted to the cell wall of transgenic
      Arabidopsis leaf cells.

PMID- 9640668
TI  - Overexpression of pyrophosphatase leads to increased sucrose degradation and
      starch synthesis, increased activities of enzymes for sucrose-starch
      interconversions, and increased levels of nucleotides in growing potato tubers.
AB  - Overexpression of inorganic pyrophosphatase (PPase) from Escherichia coli in the
      cytosol of plants (ppa 1 plants) leads to a decrease of inorganic pyrophosphate
      (PPi; U. Sonnewald, 1992, Plant J 2: 571-581). The consequences for sucrose
      starch interconversions have now been studied in growing potato (Solanum
      tuberosum L. cv. Desiree) tubers. Sucrose is degraded via sucrose synthase and
      UDP-glucose pyrophosphorylase in growing tubers, and it was expected that the low
      PPi in the ppa 1 transformants would restrict the mobilisation of sucrose and
      conversion to starch. Over-expression of PPase resulted in an accumulation of
      sucrose and UDP-glucose, and decreased concentrations of hexose phosphates and
      glycerate-3-phosphate in growing ppa 1 tubers. Unexpectedly, the rate of
      degradation of [14C] sucrose was increased by up to 30%, the rate of starch
      synthesis was increased, and the starch content was increased by 20-30% in ppa 1
      tubers compared to wild-type tubers. Reasons for this unexpectedly efficient
      conversion of sucrose to starch in the ppa 1 tubers were investigated. (i) The
      transformed tubers contained increased activities of several enzymes required for
      sucrose-starch interconversions including two- to three-fold more sucrose
      synthase and 60% more ADP-glucose pyrophosphorylase. They also contained 30-100%
      increased activities of several glycolytic enzymes and amylase, increased
      protein, and unaltered or slightly decreased starch phosphorylase, acid invertase
      and mannosidase. (ii) The transformants contained higher pools of uridine
      nucleotides. As a result, although the UDP-glucose pool is increased two- to
      threefold, this does not lead to a decrease of UTP or UDP. (iii) The
      transformants contained twofold larger pools of ATP and ADP, and ADP-glucose was
      increased by up to threefold. In stored ppa 1 tubers, there were no changes in
      the activities of glycolytic enzymes, and nucleotides did not increase. It is
      concluded that in growing tubers PPi has a wider-significance than just being an
      energy donor for specific reactions in the cytosol. Increased rates of PPi
      hydrolysis also affect general aspects of cell activity including the levels of
      nucleotides and protein. Possible ways in which PPi hydrolysis could affect these
      processes are discussed.

PMID- 9640669
TI  - Tissue-related changes in methyl-esterification of pectic polysaccharides in
      cauliflower (Brassica oleracea L. var. botrytis) stems.
AB  - Pectic substances are a major component of cell walls in vegetable plants and
      have an important influence on plant food texture. Cauliflower (Brassica oleracea
      L. var. botrytis) stem sections at different regions of the mature plant stem
      have been monitored for tissue-related changes in the native pectic
      polysaccharides. Chemical analysis detected appreciable differences in the degree
      of methyl-esterification (ME) of pectic polysaccharides. About 65% of
      galacturonic acid (GalpA) residues were methyl-esterified in floret tissues.
      Relative ME showed a basipetal decrease, from 94% in the upper stem to 51% in the
      lower-stem vascular tissues. The decrease was not related to a basipetal increase
      in glucuronic acid (GlcpA) residues. The monoclonal antibodies, JIM 5 and JIM 7,
      produced distinct labelling patterns for the relatively low-methylesterified and
      high-methyl-esterified pectin epitopes, respectively. Labelling was related to
      cell type and tissue location in the stem. Floret cell walls contained epitopes
      for both JIM 5 and JIM 7 throughout the wall. Stem vascular tissues labelled more
      strongly with JIM 5. Whereas pith parenchyma in the upper stem labelled more
      strongly with JIM 7, in the lower-stem pith parenchyma, JIM 5 labelling
      predominated. Localization of pectic polysaccharide epitopes in cell walls
      provides an insight into how structural modifications might relate to the
      textural and nutritional properties of cell walls.

PMID- 9640670
TI  - Cardenolide 16'-O-glucohydrolase from Digitalis lanata. Purification and
      characterization.
AB  - A three-step chromatographic procedure was developed for purification of
      cardenolide 16'-O-glucohydrolase (CGH) from Digitalis lanata Ehrh. leaves,
      including Phenyl-Sepharose hydrophobic interaction chromatography followed by SP
      Sepharose cation exchange and Q-Sepharose anion-exchange chromatography. Starting
      with acetone dry powder the purification resulted in an 760-fold enrichment of
      CGH. Molecular weight, substrate specificity, pH optimum and temperature
      stability of CGH were determined. Antibodies against CGH were prepared in
      rabbits. The SDS gel electrophoresis of protein extracts from leaves of D. lanata
      and other D. species showed bands at 70 kDa and 36 kDa reacting with the
      antibodies. The 70-kDa protein is the main protein stained with CGH antibodies in
      freshly prepared extracts of D. lanata. It may represent undegraded CGH. The 36
      kDa protein is enriched in aged CGH preparations. It is probably a degradation
      product. Proteins related to 70-kDa and 36-kDa bands also occur in crude protein
      preparations from leaves of D. heywoodii P. et M. Silva, D. mariana Boiss., D.
      purpurea L., and D. thapsi L. indicating that CGH is also present in these
      species. Purified CGH was digested with proteases V8 and Lys-C and the resulting
      fragments obtained were sequenced. One fragment had the typical amino-acid
      sequence of the catalytic center of family-1 glycosyl hydrolases (EC 3.2.1.x).
      Cardenolide 16'-O-glucohydrolase, like the other members of this enzyme family,
      appeared to have a glutamic acid residue directly involved in glycosidic bond
      cleavage as a nucleophile.

PMID- 9640671
TI  - [Ethics in scientific research].

PMID- 9640672
TI  - Growth and differentiation of adult Mongolian gerbil epidermal cells in culture.
AB  - A simple protocol for the growth and differentiation of adult Mongolian gerbil
      epidermal cells is reported. Insulin (8 micrograms/ml) and reduced levels of
      serum supplementation (2%) were sufficient for the maintenance of these cells in
      culture. Primary cultures were maintained as a proliferative monolayer in a
      medium with low calcium concentration (< 0.3 mM). Terminal differentiation of
      cultures was induced by raising the calcium concentration (1.6 mM) in the medium.
      These results support the concept derived from mouse epidermal cell culture that
      calcium is an important regulator of mammalian epidermal cell growth and
      differentiation. The present protocol also represents a useful tool for studies
      of mechanisms involved in epidermal cell growth and differentiation in a
      laboratory animal.

PMID- 9640673
TI  - Adult gerbil epidermal cells resistant to terminal differentiation associated
      with initiation of carcinogenesis.
AB  - In order to identify the cellular basis of the gerbil skin unresponsiveness to
      two-stage carcinogenesis, it was studied the effect of an initiating dose of
      carcinogen on the biological behaviour of gerbil skin. Treatment of adult gerbil
      epidermal cells either in vivo or in vitro with 3-methylcholanthrene yielded
      cells which were resistant to terminal differentiation induced by calcium. These
      results support the concept derived from the mouse model system of skin
      carcinogenesis in which initiation is associated with an altered program of
      epidermal differentiation. The results also suggest that relative resistance of
      gerbil skin to two-stage carcinogenesis is related to promotion stage.

PMID- 9640674
TI  - [Cyclic nucleotide phosphodiesterases: diversity, classification, structure and
      function].
AB  - During the last years there have been major advances in the knowledge of cyclic
      nucleotide phosphodiesterases. Particularly, referred to the presence of multiple
      different isozymes. Seven different phosphodiesterase gene families, have been
      described in mammalian tissues, containing several distinct genes, most of them
      expressed in different tissues as functionally unique splice variants. This
      article includes various aspects of the currently accepted nomenclature,
      structure and function of each family of phosphodiesterases. Finally, a brief
      discussion of the presence and role of these enzymes in the cell proliferation
      and differentiation processes, in parasites of the Trypanosmatidae family, is
      provided.

PMID- 9640675
TI  - [Genetic structure of the population of Guarico, Venezuela, studied through
      isonymy].
AB  - The genetic structure of the State of Guarico, Venezuela, was studied through the
      distribution of surnames from individuals above 40 years of age, obtained from
      the register of electors. The sample studied consisted in 109,200 individuals and
      14,138 different surnames. For each of the 32 counties of the State, the
      following estimators were calculated: percentage of the population included in
      surnames which appear only once (estimator A), percentage of the population
      included in the seven most frequent surnames (estimator B), the coefficient of
      consanguinity due to random isonymy (n phi ii), and Karlin and McGregors ni nu,
      an estimator of migration. The correlation between n phi ii and B was 0.97,
      indicating that 94% of the variation observed in the coefficient of consanguinity
      due to random isonymy is due to the seven most frequent surnames. The correlation
      between A and ni was 0.93, so that 86% of the variation observed in ni, is due to
      surnames which appear only once. On the other hand, correlations between A and B,
      and between n phi ii and nu were non significant (0.25 and 0.01 respectively),
      meaning that they are measuring different features of population structure: B and
      n phi ii, and v were non significant (0.25 and 0.01 respectively), meaning that
      they are measuring different features of population structure: B and n phi ii,
      isolation, and A and nu, migration. The most isolated counties of Guarico,
      according to n phi ii and B, are Santa Rita, Espino, El Calvario, Ortiz and Santa
      Maria de Ipire. Microdifferentiation of the State was studied through the
      estimation of RST, which gave a value of 0.0008. Comparing this value with those
      obtained in other Venezuelan States, it is found that Guarico, with Aragua and
      Yaracuy, are among the least differentiated States, probably because of the
      absence of important geographical barriers and the nearness to the Capital City
      of our country.

PMID- 9640676
TI  - [The canarians of San Antonio de los altos, Edo, Miranda, Venezuela. Isolation
      and marriage unions between 1900 at 1981].
AB  - We present results of a study on isolation and endogamy in San Antonio de Los
      Altos a Venezuelan town founded in 1683 by 41 Spanish families of Canarian
      origin. The study was done with the civil marital records registered during the
      years 1905 to 1981. The results show that the same few surnames cover an
      important proportion of individuals in all the periods studied, which suggests
      that these belong to the traditional families. An important endogamy is revealed
      through the frequencies of surnames, birth places of spouses, and the isonymy
      analysis, which decrease after 1960 with the rupture of the isolate. The higher
      Fn values and the predominance of some types of isonymy suggests the existence of
      preferential unions. Geographic isolation and some economic factors, such as the
      property of the land, could have favoured the isonymy and endogamy observed among
      surnames of the founders of the town.

PMID- 9640677
TI  - Foodborne intestinal parasitic protozooses.

PMID- 9640678
TI  - [Vegetables for human consumption as probable source of Toxocara sp. infection in
      man].
AB  - Although Toxocara canis life cycle is known, other possible mechanisms
      dynamically involved in its transmission to man are still ignored. The object of
      the present investigation was to search the occurrence of Toxocara sp. eggs in
      vegetables which humans consume. Five hundred and thirty six vegetables from a
      supply distribution center in Mexico City (Distrito Federal) were examined. Those
      included 212 carrots, 76 potatoes, 31 radishes, 22 mushrooms, 27 lettuces, 20
      sweet potatoes and 66 bundles of spinaches, 32 bundles of salt-worts, 29 bundles
      of coriander, and 21 bundles of purslane. Each unit or bundle was washed with 50
      ml of sterilized water, allowing sedimentation at room temperature for 8 hours.
      Five ml of sediment were centrifugated at 3,000 r.p.m. for 5 minutes. Sediment
      was examined in lugol stained fresh plates through light microscopy, which turned
      to be Toxocara sp. eggs were found only in two vegetables: 1.9% of carrots and
      6.5% of radishes. Toxocara sp. eggs were: 66.7% recently emitted and 33.3%
      embryonated. Other parasite elements were: Ascaris lumbricoides eggs 1.9% in
      carrots, 2.6% in potatoes, 9.1% in mushrooms, 6.9% in corianders, 20.0% in sweet
      potatoes and 6.1% in spinachs. Entamoeba histolytica cyts were found in 0.9% of
      carrots. Soil contamination with Toxocara sp. eggs from parasitized dogs or cats,
      or with either sewage systems or contaminated water where vegetables for human
      consumption are grown, play a role as a transmission mechanism must be deeperly
      studied since 33.3% of Toxocara sp. eggs found contained larvae, potentially
      infective to man.

PMID- 9640679
TI  - [Cryptosporidiosis in children with acute diarrhea from Ciego de Avila province,
      Cuba].
AB  - An epidemiological and clinical study of criptosporidiosis in children from Ciego
      de Avila province was carried out from 1987 to 1994. During this period 14,895
      children with acute diarrhea were studied. Cryptosporidium sp. oocysts were found
      in the feces of 1,256 (8.4%) of them. Isolated cases prevailed over outbreaks,
      being the incidence rate proportional in both urban and rural areas. Seventy nine
      point seven per cent of infected children were less one year old, predominating
      the age group 6-11 months old. No influence of seasons on the occurrence of the
      parasitose was observed. The most frequently detected symptoms and signs were
      diarrhea, vomits and loss of weight. The main epidemiological factors were: 81.0%
      of ill children drank water directly from the aqueduct, 12.8% lived in
      overcrowded conditions, 11.0% had animals and 10.7% attended nursery schools.

PMID- 9640680
TI  - [Immunodiagnosis in 647 suspected clinical cases of toxoplasmosis].
AB  - Though Toxoplasma gondii can cause severe pathology in human, in most of the
      cases it produces only asymptomatic infection. So, it is important to dispose
      some methods capables to discriminate between acute and chronic infections. An
      indirect hemagglutination test (IHAT), dye test (DT) and complement fixation test
      (CFT) were performed in 647 sera from patients suspected of having toxoplasmosis
      infection. IHAT and DT titer > or = 4 and CFT > or = 5 were considered positive.
      Titers were classified as follows: low (4-16), median (64-512) and high (> or =
      1000) for IHAT and DT. The pathologies for demanding these serological tests
      were: adenopathies (58), nephropathies (72), neuropathies (30), obstetrical
      problems (65), opthalmopathies (147), AIDS (237) and miscellaneous (37). Global
      positivity of 49.5% and 4.5% for IHAT/DT and CFT respectively were found. The
      positivity for the different groups were: adenopathies (48.3% and 13.8%),
      nephropathies (43.1% and 1.4%), neuropathies (26.7% and 3.3%), obstetrical
      problems (40.0% and 0.0%), ophthalmopathies (59.9% and 8.2%), AIDS (52.1% and
      2.5%) and miscellaneous (40.5% and 2.7%) for IHAT/DT and CFT respectively. Low
      and median titers for IHAT/DT were found in 81.3% of cases. A high agreement in
      frequency of concordant and discordant titers of IHAT/DT and CFT, indicating a
      recent or acute infection was observed. This fact was more relevant in
      adenopathies, ophthalmopathies (uveitis) and AIDS groups.

PMID- 9640682
TI  - [Spirocamallanus hilarii (Nematoda, Camallanidae) fresh water fishes parasite
      from the dam of Termas de Rio Hondo, Santiago del Estero, Argentina].
AB  - Spirocamallanus hilarii (Nematoda, Camallanidae) is cited parasitizing five fresh
      water fish species: Salminus maxillosus Leporinus obtusidens, Hoplias malabaricus
      malabaricus, Oligosarcus jenynsii and Pimelodus albicans, captured in Termas de
      Rio Hondo pond, province of Santiago del Estero, Argentina. Morphologic and
      morphometric parasitological studies were done. The specimens described were
      drawned and photographed. In addition, the following parasitic infection indexes
      were calculated: Prevalence 26.5%, Mean 6.6 and Maximum Intensity 27.

PMID- 9640681
TI  - [Cercaria chaetotaxy of 2 Venezuelan strains of Schistosoma mansoni].
AB  - By means of the silver impregnation of two lots of Schistosoma mansoni cercariae
      belonging to the strains: JR (32 cercariae) and C5 (45 cercariae), the number and
      pattern of disposition of the argentophillic papillae were determined with the
      following results: Average number of total dorsal papillae: 12.1 (JR strain) and
      12.0 (C5 strain); the variation coefficients in this surface were less than 4%
      (JR strain) and bigger in JR than C5 strain. Average number of total ventral
      papillae: 12.15 (JR), 11.97 (C5); maximum value of the variation coefficient:
      6.4% (JR), higher in JR than C5 strain. When the ventral surface was classified
      in four quadrants, the average number of papillae by quadrant was: quadrant A:
      1.15 (JR) and 1.06 (C5): B: 1.06 (JR) and 1 (C5); C: 4.97 (JR) and 4.96 (C5); D:
      5.03 (JR) and 4.98 (C5). The variation coefficients were higher in the A and B
      ventral quadrants, reaching maximum values of 31.9%, and 61.0% for the posterior
      quadrants C and D. When the ventral surface was divided in three equal parts for
      determining the position of the most variable papillae of this area, the greatest
      value of the variation coefficients obtained were for the 2nd thirds of the
      cercariae: 89.8% and 76.8% for C5 strain and 43.5% and 56.8% for JR strain. In
      relation to the total lateral papillae, the average numbers were: 17.0 (JR) and
      16.6 (C5), with a maximum value of variation coefficient of (8.1% (C5). The
      average total number of papillae of the tail were: 25.6 (JR) and 26.1 (C5) for
      the ventral surface and 20.72 (JR) and 21.33 (C5) for the dorsal papillae. The
      comparison between the percents of the cercariae of two S. mansoni strains with
      more than 1 papillae on the anterior ventral quadrants A or B (94% JR and 34%
      C5), resulted with significant differences (P < 0.05).

PMID- 9640683
TI  - [Acuariosis in Numida meleagris (Aves: Numididae)].
AB  - A case of gastric nematodiasis is described in a gineafowl (Numida meleagris)
      from the Municipal Zoo, Presidencia Roque Saenz Pena (Chaco) Argentina. Nematodes
      obtained from the glandular stomach were observed in optic microscopy. According
      to their morphometric characteristics and location in the definitive host, were
      identified as belonging to the family Acuariidae, subfamily Acuariinae, species
      Dispharynx nasuta Rudolphi, 1819.

PMID- 9640684
TI  - [Pediculosis capitis, a permanent and renewed problem].
AB  - Pediculosis capitis is still a world-wide public health problem. Pediculus
      humanus capitis, the agent, is a permanent and specific human blood-sucking
      ectoparasite extended throughout the world. By the end of sixties and begin of
      seventies an important increase of prevalence of this parasitose was observed in
      many countries and lice infestation throughout the world was estimated to run
      into hundreds of millions. Decline of personal hygiene, increased promiscuity and
      long hairstyle, particularly in adolescents and young people seemed to mark the
      beginning of this new situation. At present pediculosis capitis not only affects
      low socio-economic groups, but middle and high level groups. Several observations
      have shown a clear relationship between long hair and pediculosis capitis.
      Prevention of pediculosis capitis is supported by community health education,
      stressing the personal hygiene, the use of reasonable short hair and frequent
      washing of head.

PMID- 9640685
TI  - [Prevalence of Blastocystis hominis infection in schoolchildren from Bolivar
      City, Venezuela].
AB  - Blastocystis hominis is found in about 25% of feces in normal asymptomatic
      people. Its pathogenic role is still discussed. A prospective study was performed
      to determine the prevalence of B. hominis infection in schoolchildren from
      Bolivar City. We evaluated 446 children, between five and fourteen years old,
      both sexes, using direct examination of feces and Willis Method. They were also
      evaluated clinically. Results showed that B. hominis had a prevalence of 16.8%.
      We did not find a statistically significant association between sex (P > 0.05) or
      age and infection with B. hominis (x2 = 1.94 g.l = 4). In 39 schoolchildren
      (52.0%) we identified other parasites along with B. hominis, the most frequent
      was Trichuris trichiura as helminth and Giardia lamblia as protozoan. We observed
      B. hominis alone in 36 cases (48.0%). There was a spectrum of clinical symptoms
      in 41 (54.7%) of all children evaluated. Diarrhea was the most frequently
      clinical manifestation observed. Other studies are necessary to determine
      clinical relevance of B. hominis in school population in Bolivar City.

PMID- 9640686
TI  - [Frequency of human trichinosis in Concepcion and Arauco, Chile: study in
      autopsied persons at the Concepcion Medico-Legal Service. June 1996-March 1997].
AB  - The frequency of trichinosis was determined in 300 dead persons, residents in the
      provinces of Concepcion and Arauco, and requiring necropsy at the Servicio Medico
      Legal of Concepcion. Diaphragm muscle samples were taken from June 1996 to March
      1997. The diagnosis was made by trichinoscopy and artificial digestion
      techniques. Five samples (1.67%) were positive. There was not differences between
      sexes. Positive cases were found mainly among 30 to 49 years old people belonging
      to middle-lower class. Both diagnostic techniques showed different sensitivity as
      a consequence of the parasitic load and on the contrary, the artificial digestion
      was less sensitive when the cyts were fully calcified.

PMID- 9640687
TI  - [Contribution to the morphological description of Tylodelphys barilochensis and
      Tylodelphys crubensis (Trematoda, Diplostomidae) encephalon parasites of Galaxias
      maculatus (Teleostei, Galaxiidae)].
AB  - Taxonomic characteristics, for species identification, of metacercarie of T.
      barilochensis and T. crubensis found in the encephalon of the fish Galaxias
      maculatus, not included in the original descriptions, particularly those
      concerning to the excretory system, are described.

PMID- 9640688
TI  - [Development of tympanoplasty].

PMID- 9640689
TI  - [The results of tympanoplasty with titanium prostheses].
AB  - In order to improve the hearing results of tympanoplasty, we performed the
      operation on 113 cases (124 ears) by using ossicular replacement prostheses made
      of Titanium. The results demonstrated that among all the operated ears, 73/124
      (58.9%) had obtained a narrow gap (< 20 dB HL) between BC and AC, 89/124 (71.8%)
      had regained socially acceptable hearing ability. The total effective rate of
      hearing gain (> 10 dB HL) was 115/124 (92.7%). No reject reaction and recurrent
      cholesteatoma were found. This operation method, based on animal experiments and
      applied anatomic study of human suprastapedial structure, resulted in a high
      effective rate and maked hearing improvement with a relatively large magnitude.
      It was because of the application of a new material-Titanium, which has high
      biocompatibility with human body tissues. The ossicular replacement prosthesis
      was appropriately designed and delicately manufactured. It fitted well and could
      be tightly joined to the suprastapedial structure, and uneasy to be displaced. In
      addition, we adopted the method of enlarging tympanic isthmus, that lead to well
      aeration in mastoid and attic, thus set the tympanic membrane to the best state
      of mobility. All these contributed to the effective hearing gain.

PMID- 9640690
TI  - [Cholesterol granulomatous tympano-mastoiditis].
AB  - In order to investigate the early diagnosis and proper management of the
      cholesterol granulomatous tympanomastoiditis, 6 cases verified by pathology and
      surgery were reviewed. All of these cases had a longterm or a historical otitis
      media. Among them, different clinical features were presented, such as chronic
      serous otitis media, idiopathic blue eardrum, or as a primary occupying lesion of
      the middle ear. Depend on the extension of the disease, surgical procedure varied
      in the 6 cases, including exploratory tympanotomy, ventilation tube insertion,
      antroatticotomy, simple mastoidectomy, and radical mastoidectomy. Postoperative
      follow up for at least one--7 year showed no recurrence, and hearing improvement
      in 5 cases. The clinical basis of the diagnosis and management of this disease
      were also discussed.

PMID- 9640691
TI  - [Mastoid pneumatization and secretory otitis media].
AB  - 75 ears of 44 patients with secretory otitis and 80 ears of 40 patients with
      normal ear were observed and reserched. All of the cases were received X-ray
      examination of mastoid process in Schuller's lateral projection. The size of the
      air cell system was obtained by planimetry: the method what was originally
      devised by Diamant. The outline of the mastoid air cell system (MACS) was marked
      out on the radiograph and then transferred to graph paper where the number of mm2
      can be counted directly. According to measuring the planimetric area of MACS. The
      mastoids were divided into two categories: pneumatization type and
      nopneumatization type. 5 of 69 ears with pneumatization mastoid (7.2%) were
      secretory otitis, while 70 of 86 ears with nopneumatization (81.4%) were
      secretory otitis. It was significantly different (P < 0.001) camparing the number
      of ears with secretory otitis. We believe that the degree of mastoid
      pneumatization is associated with the occurring and prognosis of secretory
      otitismedia.

PMID- 9640692
TI  - [A report of 164 cases of Bell's palsy].
AB  - In order to research the relationship between various methods of treatment and
      their prognosis on Bell's palsy, 164 cases of Bell's Palsy were reviewed.
      According to the results of ENoG test, 164 cases were divided into three groups
      A, B1 and B2. Group A: the paretic side ENoG loss was less than 90%, group B1:
      the ENoG loss was more than 90% and without surgical decompression of facial
      nerve, group B2: the ENoG loss was more than 90% and with surgical decompression.
      All of the patients had follow up for 1-3 years or even longer after onset. The
      grades of recovery of facial function were evaluated by modified classification
      system as originally proposed by Portmann. The facial function of 77 cases of
      group A were recovered satisfactorily except 3 patients, the average points were
      19.22 +/- 1.18. The average points of group B1 (41 cases) and B2 46 cases were
      14.4 +/- 3.49 and 15.4 +/- 2.08 respectively. Comparing the results with group
      B1, B2 and A, there was no statistical significant difference (P > 0.05) between
      group B1 and B2, but the results of group A were statistically significant better
      than group B1 and B2 (P < 0.01). The prognosis of Bell's palsy might mainly
      depend on the degree of degeneration of facial nerve. A satisfactory recovery can
      be expected when ENoG test loss was less than 90%. If ENoG loss was more than
      90%, neither surgical decompression nor steroids therapy could change the
      prognosis statistically.

PMID- 9640693
TI  - [Nasal septal deviation in fetuses].
AB  - To investigate the etiology of nasal septal deviation, twenty-four fetal
      sinonasal specimens aged between 8-40 weeks of gestation were studied under light
      microscopy. Sixteen fetal heads aged between 32-40 weeks were examined using 2.7
      mm 5 degrees Wolf endoscope. Five of 24 fetal sinonasal specimens were confirmed
      histopathologically to have deviated nasal septum. 1 of 16 fetal heads was
      considered to have nasal septal deviation. The existence of nasal septal
      deviation in fetuses was confirmed. To explain the embryogenesis, we suggested
      that maldevelopment of vomeropalatal complex is responsible for the formation of
      nasal septal deviation in fetuses.

PMID- 9640694
TI  - [Bromodeoxyuridine immunohistochemical observation of sensory epithelium repair
      after ototoxic destruction in the crista ampullaris of guinea pigs].
AB  - In this in vivo study we investigated the proliferation of crista ampullaris in
      guinea pigs after Gentamicin intoxication by BrdU immunohistochemical observation
      and semi-thin sections. The experimental animals were given a single
      intraperitonial injection of BrdU at a dose of 150 mg/kg body weight before
      subsequently killed at 1, 3, 7, 14 and 22 day post-treatment (PT). Supporting
      cell proliferation was evident by BrdU immunoreactivity in the chromatin material
      of dividing cells at 7 and 14 day PT. The results demonstrated that the crista
      ampullaris of guinea pigs had repaired by supporting cell mitosis.

PMID- 9640695
TI  - [DNA replication and cellular proliferation in the noise damaged basilar papillar
      of chicks].
AB  - An acoustic trauma model for study of the repair of the auditory epithelia was
      established in postnatal 8-14 days chicks. The animals were continuously exposed
      to the wide band noise at 115 dB (A) for 72 hours. The tracer of DNA replication
      [3H] thymidine (3H-dR) was given in vivo or in vitro during or after exposure.
      The basilar papilla were cultured and processed with autoradiographic technique.
      The results demonstrated that at 48 hours following initial labelling of tracer,
      the incorporation of 3H-TdR was found over the nucli of supporting cells (or
      precursor cells) in the injured region of basilar papilla. The labelled hair
      cells appeared at 96 hours near the labelled supporting cells. Until the fifth to
      sixth days of culturing, the regenerated hair cells were still immature
      morphologically. No sign of labelled hair cells were detected in the control
      animals. Our findings indicated the potential capability of cellular
      proliferation and DNA replication in damaged auditory epithelia in vitro. Some
      kind of supporting cells in damaged region could be the precursors for
      regenerating hair cells. The positive cells labelled with 3H-TdR migrated to the
      surface of basilar papilar and differentiated into hair cells eventually.
      Therefore, it could be speculated that a homogeneous relationship may exist
      between labelled supporting cells and labelled hair cells.

PMID- 9640696
TI  - [A study of tracheal defect repair in rabbits with collagen-hydroxylapatite].
AB  - An artificial material composed of collagen-Hydroxylapatite (C-HA) was used to
      repair the tracheal defect of rabbits. There was no reaction, no absorption and
      no particle detachment after the C-HA was implanted. We also found that the
      tracheal mucosa could grow over the surface of C-HA. The result suggested that
      the C-HA can be used as a material for repairing the tracheal defect of the
      tracheostenosis.

PMID- 9640697
TI  - [Histiocytosis X of the temporal bone].
AB  - Histiocytosis X (HX) is a rare disease. There are many questions and debates in
      its etiology, pathology, clinical type and therapy. To enhance the recognition of
      otolaryngologists in HX of the ear and temporal bone and the level of diagnosis
      and therapy, 30 years' results of 21 patients with HX of the ear and temporal
      bone proved by histiopathology were reviewed, 18 patients were cured (85%), 6
      cases were residual of diabete insipidus and dwarfism (28%), 3 cases died (14%).
      The clinical classification system should be based on the extention of diseases.
      Surgical curettage, radiation therapy are mainstays of treatment; chemotherapy
      should be used in patients with aggressive and disseminate diseases and etiology
      of histiocytosis should be studied on immune system that potentially aid in
      therapy.

PMID- 9640698
TI  - [Medical imaging research on idiopathic hemifacial spasm].
AB  - In order to have a medical imaging examination for idiopathic hemifacial spasm
      before surgery, we designed a new method by using vertebroarterial DSA and
      vertebroarterial CTA based on an aired cisternapontis, 36 patients were examined
      since 1989 and the compression of the facial nerve from brain stem to porus
      acousticus internus was showed clearly in all the cases. The arteries responsible
      for the compression were cerebellar inferior posterior (55.6%), cerebellar
      inferior anterior (44.4%), auditory internus (25.0%) and vertebroarterial
      (11.1%), 36% of all the cases had more than one responsible arteries, 22.2% cases
      had only one compression point, 38.9% had two points, 25.0% had 3 and 13.9% had
      more. 85.7% of the compression points located in the root zone and 14.3% near the
      porus acousticus internus. 24 cases were treated with decompression surgery, it
      indicated that the compression conditions just met the medical imaging
      examinationg results. After surgery the symptom disappeared in 23 cases and
      remarkably released in one case with no death case. We believed that this method
      might be helpful to idiopathic hemifacial spasm decompression surgery and other
      surgeries in the CP angle.

PMID- 9640699
TI  - [Treatment outcome of 1,000 cases of endoscopic sinus surgery].
AB  - To assess the treatment outcome of endoscopic sinus surgery (ESS), 1,000 patients
      with chronic sinusitis and nasal polyp treated between November 1991 and January
      1995 were included in this study. Among them, 754 patients (64.8%) had previous
      operations from 1 to 25 times with an average of 3.7. Before ESS, axial and
      coronal CT scans were obtained (window width: 1,000 HU, window level: +90 HU;
      section thickness: 2 mm with 12 to 16 sections). Patients with clinical stages
      from I to IV were 9.9%, 21.0%, 15.0% and 54.1% respectively. Bilateral ESS was
      performed in 95% patients, septoplasty in 27.6%, middle meatal antrostomy in
      78.5%. The clinical cure rate was 84.0%, 557 patients were considered as primary
      healing, 283 patients delayed healing and 160 patients had persistent
      inflammation. Complications were noted in 18 patients. Bleeding during ESS varied
      from 10 to 1,800 ml (average 180 ml). The indications, preoperative evaluation,
      control of bleeding, prevention of complications and prognosis were discussed in
      detail. The article indicated that the important factors to increase the cure
      rate are postoperative follow-up and systematic treatment.

PMID- 9640700
TI  - [Nasal polyps of olfactory sulcus].
AB  - To explore the origin of olfactory sulcus polyp (OSP) and observe the recovery of
      olfaction after functional endoscopic sinus surgery, fifty-nine olfactory sulcus
      polyps in 31 patients were reviewed. The origin of OSP was carefully observed. In
      these patients 69.5% (41 sides) originated from the mucosa of posterior ethmoid
      sinus, including the superior meatus (23 sides) and ethmoid cells near the ostia
      (18 sides). OSP originated from middle turbinate (8 sides) and superior turbinate
      (4 sides). Six OSP originated from the mucosa of both ethmoid and sphenoid sinus.
      Olfactory changes were dynamically observed after endoscopic sinus surgery in 26
      patients. The smell improved significantly in 26 sides (52.0%) within three
      months. The olfaction improved slowly in those patients with recurrent polyps and
      polysinusitis associated with polyps. We suggest that minimal endoscopic sinus
      surgery is the treatment of choice for OSP.

PMID- 9640701
TI  - [Extended vertical partial laryngectomy for treatment of the glottic cancer with
      T3 category].
AB  - From June 1981 to December 1992, 32 patients of glottic cancer with T3 category
      were treated by extended vertical partial laryngectomy, i.e. vertical
      laryngectomy plus the resection of the arytenoid and part of the cricoid plate.
      The laryngeal defect was reconstructed by an osteomuscular flap. The 3- and 5
      year survival rates were 78.1% and 73.9% respectively. The decannulation rate was
      81.3%. The voice was satisfactory in 84.3%. All patients resumed mouth-food
      taking. The authors conclude that selective glottic cancer of T3 category treated
      with extended vertical partial laryngectomy, which preserves the functions of the
      larynx and improves the quality of the life, is feasible and acceptable.

PMID- 9640702
TI  - [The surgical treatment for the epiglottic cancer extended to the base of
      tongue].
AB  - 26 cases of the epiglottic cancer extended to the base of the tongue were studied
      retrospectively. Among them, 14 were male and 12 female. The age varied from 43
      to 62. Besides two cases who underwent total laryngectomy, the other twenty-four
      were treated with supraglottic horizontal partial laryngectomy or
      horizontovertical subtotal laryngectomy and resection of part of base of the
      tongue. 11 cases received bilateral radical neck dissection (RND) and 10 cases
      unilateral RND simultenously. The results showed twenty-four cases had resumed
      speaking ability, twenty had been decannulated and restored the laryngeal
      functions. The 5-year survival rate was 57.9% (12/19). It was concluded that
      transpharyngeal approach was reasonable for supraglottic horizontal partial
      laryngectomy associated with the resection of the base of the tongue.

PMID- 9640703
TI  - [Endoscopic CO2 laser treatment for the decannulation difficulty after vertical
      laryngectomy].
AB  - Sixteen patients with the decannulation difficulty after vertical laryngectomy
      were treated by endoscopic CO2 laser. The rate of decannulation was 87.5%
      (14/16). The curative effect was stable after 1-3 years. The causes of the
      decannulation difficulty included the over growth of granulation tissue, scar
      formation and bulky of the muscle flap. The result showed that endoscopic CO2
      laser is an effective modality in the treatment of the decannulation difficulty
      after vertical laryngectomy.

PMID- 9640704
TI  - Telemedicine and developing countries. A report of study group 2 of the ITU
      Development Sector.
AB  - While there are significant potential advantages and benefits from telemedicine,
      the evidence of its cost-effectiveness and sustainability is meagre. This is
      because much of the telemedicine activity so far has been in the form of pilot
      projects of demonstrations in universities and hospitals with subsidized funding
      from government or other sources. The number of self-sustaining, commercial
      applications of telemedicine is still very small. Telemedicine undoubtedly yields
      cost savings in certain circumstances, but often the savings and benefits accrue
      to those who do not have to pay for the service. Thus, few service providers have
      found a way to recover their costs (and make a profit) from those to whom they
      provide their service. Even fewer countries have actually budgeted for the
      provision of telemedicine as a service widely available to their citizens.
      Nevertheless, with the rapidly declining cost in hardware and telecommunications,
      the level of interest and the corresponding activity in telemedicine is rising
      rapidly. Most of the telemedicine experience to date has been in the
      industrialized world. It is apparent that the first requirement of developing
      countries is for more information about telemedicine, what it is, and how it
      might be able to help solve some of the shortages in medical and health care.
      Given the potential of telemedicine to facilitate the provision of medical
      information and health care in rural areas, it seems useful for developing
      countries to undertake pilot projects in order to evaluate its potential and cost
      benefits. The results of such pilot projects could be part of the development of
      a national health for all policy which takes telemedicine into account. In view
      of the other priorities of developing countries, especially those of the least
      developed countries, financing telemedicine activity is likely to remain a
      challenge for some time to come. Funding from external donor agencies may well be
      necessary, but local commitment and participation in pilot projects is essential
      if the project is to have a chance of success. As telemedicine requires a
      multidisciplinary approach, the active participation of telecommunication
      operators must be assured. Despite some false starts in the deployment of
      telemedicine as a continuing service to the general population--as opposed to a
      few well-to-do clients--telemedicine has great potential to improve access to
      health care and to contain costs in developing countries.

PMID- 9640705
TI  - A survey of research in telemedicine. 1: Telemedicine systems.
AB  - Published work in telemedicine has been surveyed in order to consider the range
      of current research, highlight some pitfalls and point out areas where it seems
      that more work is required. This article deals with tests of the safety and
      efficacy of telemedicine systems. This work can be seen as moving through three
      phases: first, identify the technical specification of equipment required for the
      particular telemedicine application; second, test that this is appropriate in
      particular settings; third, establish a set of standards and guidelines to ensure
      that the telemedicine system is used to the best advantage. Work in teleradiology
      seems to be in the second phase. Work in teledermatology, for example, is still
      in the first phase. Telemedicine is an important and growing area of academic
      research. The quality of the research ought also to be increasing. While there
      have been a number of well designed, robust studies with clear conclusions that
      show the value of telemedicine in certain settings, much more remains to be done.

PMID- 9640706
TI  - The legal and ethical aspects of telemedicine. 2: Data protection, security and
      European law.
AB  - The electronic record may be subject to abuses that can be carried out on a large
      scale and cause great damage. A wide range of data protection and information
      security measures will need to be taken to ensure the quality and integrity of
      such records. A European Union directive was formally adopted in 1995 which sets
      the obligations of those responsible for data processing as well as a number of
      important rights for individuals. The responsible teleconsultant or medical
      officer, as the data controller, must make sure these measures are enforced. In
      the case of the transmission of medical records to another location, the original
      data controller may remain liable for abuses. But as different elements of the
      records are spread throughout the different departments of a hospital or across
      different geographical locations, it may become difficult to ascertain who is
      responsible for protecting and controlling what. To this end, the designation of
      liability by contractual means, between the hospital and remote users of a
      telemedicine network, would be the clearest and most straightforward way of
      achieving uniformity and predictability in terms of the distribution of
      responsibility for data protection and security.

PMID- 9640707
TI  - Teleradiology: a review.
AB  - Teleradiology, like telemedicine generally, has arisen because of the shift to
      digital communication and the demand for equal access to medical care. Unlike
      much of telemedicine, teleradiology can be shown to be cost-effective in many
      situations, particularly if the alternatives are to transport the X-ray film to a
      radiologist or to use the services of a visiting radiologist ('circuit riding').
      A teleradiology system consists of an image-acquisition section and an image
      display section, connected by a communications network. Considerable technical
      and clinical standardization work has been carried out (e.g. by the American
      College of Radiology) and commercial teleradiology systems are now available from
      a number of manufacturers. Up to 1994, more than 7000 teleradiology systems had
      been sold by the two largest manufactures. Technology trends suggest that it will
      soon be common for clinicians to view digital radiographs from outside radiology
      departments and probably from outside a hospital environment as well.

PMID- 9640708
TI  - Patient satisfaction with realtime teledermatology in Northern Ireland.
AB  - Teledermatology consultations were organized between two health centers and two
      hospitals in Northern Ireland using low-cost videoconferencing equipment. A
      prospective study of patient satisfaction was carried out. Following each
      teleconsultation, patients were asked to complete a questionnaire assessing their
      satisfaction with the service. Over 22 months, 334 patients were seen by a
      dermatologist over the video-link, and 292 patients (87%) completed the 16-item
      questionnaire. Patients reported universal satisfaction with the technical
      aspects of teledermatology. The quality of both the audio and the display was
      highly acceptable to patients. Personal experiences of the teledermatology
      consultation were also favourable: 85% felt comfortable using the video-link. The
      benefits of teledermatology were generally recognized: 88% of patients thought
      that a teleconsultation could save time. Patients found the teledermatology
      consultation to be as acceptable as the conventional dermatology consultation.
      These findings suggest overall patient satisfaction with realtime
      teledermatology.

PMID- 9640709
TI  - Pathologists' attitudes to implementing telepathology.
AB  - If pathologists will benefit so much from using telepathology, why is it taking
      so long to be introduced? This question has been discussed between experts, but
      the potential users are rarely asked for their opinions. A questionnaire was sent
      to the 256 members of the Austrian Society of Pathology; this addressed general
      aspects of telemedicine, telepathology in frozen-section services and expert
      consultation, videoconferencing technologies, teleteaching and teletraining. The
      response rate was 46%. In general, the pathologists thought that telemedicine
      could become valuable in their daily routine. However, pathologists were most
      afraid of sampling errors in remote diagnosis and would not readily accept an
      alternative to the conventional method of looking at a sample. This is only
      possible using realtime, remotely controlled microscopes. Telepathology systems
      providing only still images would not be acceptable to most respondents. There
      was interest in the use of videoconferencing for clinicopathological conferences.
      Teleteaching and teletraining were seen as welcome additional techniques, but
      were nevertheless judged unable to replace classical methods of teaching and
      training.

PMID- 9640710
TI  - Planning criteria for multicentre, multilingual telemedicine conferences.
AB  - The international telemedicine conference Chinese TeleMed 96 was held in November
      1996. This three-way teleconference included delegates in London (where the
      international telemedicine conference TeleMed 96 was taking place) and medical
      staff from one Beijing hospital and one Hong Kong medical faculty. In total, over
      1000 health-care personnel across eight time-zones participated. The event
      demonstrated that the quality of teleconferencing technology was suitable for
      medical teaching, for providing medical consultations to remote locations and for
      stimulating medical exchanges. In general, planning a telemedicine conference
      requires a longer lead time, a wider representation of expertise in the
      organizing committee and more financial resources than conventional conferences.
      It is recommended that the aim and format of a telemedicine conference be
      determined at least one year before the target date. Criteria for improving the
      preparation of such conferences have been identified and a set of guidelines for
      future conference organizers has been drawn up.

PMID- 9640711
TI  - Videoconferencing and the hard of hearing.

PMID- 9640712
TI  - The diffusion of telemedicine: theory into practice.

PMID- 9640713
TI  - Telemedicine: university-level education in Finland.

PMID- 9640714
TI  - Transmission of medical data from an aircraft.

PMID- 9640715
TI  - A pilot study of tele-ophthalmology outreach services to primary care.
AB  - We have begun a randomized study of tele-ophthalmology. General practitioners in
      two participating health centres in the Negev region of Israel, serving a local
      population of 40,000, were invited to participate. The study group consisted of
      50 consecutive patients attending the general eye outpatient clinic and 50
      consecutive patients suffering from various retinal diseases attending a hospital
      outpatient clinic. The initial assessment was carried out via the tele
      ophthalmology system. There was then a face-to-face re-examination of the same
      patients, in randomized order, by the same ophthalmologist on the same day, at an
      outpatient ophthalmology clinic.

PMID- 9640716
TI  - Preliminary results from the Northern Ireland arms of the UK Multicentre
      Teledermatology Trial: is clinical management by realtime teledermatology
      possible?
AB  - Results from phase 1 of the UK Multicentre Teledermatology Trial demonstrated the
      diagnostic accuracy of realtime teledermatology using low-cost equipment. Phase 2
      of the trial aimed to assess its effectiveness as a management tool for
      dermatological disease. Teledermatology consultations were organized between two
      health centres and two hospitals in Northern Ireland using low-cost
      videoconferencing equipment. For 205 patients seen by a dermatologist over the
      video-link a diagnosis and management plan were recorded. A subsequent face-to
      face consultation was arranged on the same day to confirm the diagnosis and
      treatment regime. A comparison of these management plans revealed that the same
      plan was recommended in 64% of cases; the teledermatologist was unable to
      advocate a suitable management plan in 19% of cases; a suboptimal treatment plan
      was suggested by the teledermatologist in 6% of cases; and in 11% of cases, the
      teledermatologist suggested an inappropriate treatment plan. These findings
      indicate that appropriate clinical management was possible in approximately two
      thirds of dermatology consultations via the video-link.

PMID- 9640717
TI  - Transmission of electrocardiograms from a moving ambulance.
AB  - Delay is the enemy for patients with acute myocardial infarction. It would be
      helpful for the hospital cardiologist to interpret the patient's
      electrocardiogram (ECG) before the arrival of the ambulance. The aim of our study
      was to determine whether ECG transmission from an ambulance is feasible and to
      assess the time savings. An ambulance was equipped with an ECG recorder, which
      was connected to a notebook computer and coupled to a cellular telephone for
      transmission to a hospital-based station. Paramedics needed 2 min (SD 0.5) to
      record the ECG on the move and 34 s (SD 14) to transmit it. The ambulance arrived
      15.5 min (SD 6.5) after reception. The time between arrival and ECG diagnosis,
      for a control group patient, was approximately 9.5 min (SD 3.5). Therefore, pre
      hospital ECG diagnosis took place 25 min (SD 7.5) before in-hospital diagnosis.
      We conclude that ECG transmission from a moving ambulance is feasible, reduces in
      hospital delays and allows faster triage in critical cardiac cases.

PMID- 9640718
TI  - Trans-telephonic electrocardiographic monitoring--experience in India.
AB  - A centre for trans-telephonic electrocardiographic monitoring (TTEM) was
      established at the Escorts Heart Institute in May 1996. We have reviewed our
      experience in the first 398 patients. There were 321 males (81%) and 77 females
      (19%); their age range was 1 month to 95 years. Sixty-five per cent of patients
      were from New Delhi, while the remainder were from other cities in India and
      abroad. As well as follow-up of patients after discharge, the system was used for
      the evaluation of chest pain, palpitation, chronic angina, arrhythmias, and
      pacemaker implants. Out of 664 symptomatic transmissions, 510 (77%) were for
      cardiac symptoms like chest pain (309), palpitation (90), uneasiness (61),
      dizziness (28) and breathlessness (22); the other 154 (23) were for non-cardiac
      symptoms like stitch pain and backache (51), typical chest pain (39), weakness
      and fever (45), and sweating (19). The majority of patients with chest pain
      (84%), palpitation (78%) and dizziness (75%) transmitted their electrocardiograms
      within one hour of the onset of the symptoms. Out of 664 symptomatic
      transmissions, 531 required either reassurance or drug-dose adjustment by
      telephone and 97 were called to the outpatient department on an elective basis.
      Immediate hospitalization was advised for 36 patients, for acute management of
      their symptoms. TTEM was useful in avoiding 628 unnecessary visits to the
      hospital, while 36 patients were immediately hospitalized for acute care.

PMID- 9640719
TI  - Telemedicine in primary care in Israel.
AB  - A primary-care teleconsulting system was established between an academic family
      medicine centre and a clinic about 50 km away. The videoconferencing units were
      connected at 384 kbit/s. Seven patients were examined by a physician in the
      clinic and then examined by a consulting physician using the telemedicine system.
      Four other patients were examined through the telemedicine system first and by a
      local physician later. The telemedicine consultation solved five of the patients'
      medical problems. The waiting period before receiving expert medical consultation
      was reduced. There was full patient satisfaction regarding this method of
      consultation, patient 'run around' was avoided and patients felt at ease. The
      telemedicine consultation process improved the patient-physician bond and the
      attending physician's level of confidence.

PMID- 9640720
TI  - Cost-effectiveness analysis of telemedicine.
AB  - There are a number of different costs associated with the development and
      operation of telemedicine services. A model is proposed in order to assist in
      strengthening the evidence base for telemedicine. It includes the following
      components: project establishment costs; equipment costs; maintenance costs;
      communication costs; staffing costs. All need to be considered in arriving at an
      annual cost figure for operating a telemedicine service. The inclusion of all
      these costs, prepared in the standard manner outlined in the model, will ensure
      that a realistic cost figure is available when evaluating the cost-effectiveness
      of a telemedicine service.

PMID- 9640721
TI  - A randomized controlled trial of telemedicine in an emergency department.
AB  - A prospective study of emergency department telemedicine was carried out at two
      hospitals in northern New Jersey. One hundred and twenty-two patients met the
      inclusion criteria. One hundred and four (85%) consented to participate, with 54
      being randomized to the telemedicine group and 50 to the control group. Four
      patients did not complete the protocol. No significant differences were seen
      between the groups for: occurrence of 72 h emergency department return visits (0%
      vs 0%); need for additional care (2.3% vs 2.4%); positive patient-physician
      interaction (98% vs 100%); positive patient-nurse interaction (98% vs 98%);
      positive overall patient satisfaction (98% vs 95%). The average patient
      throughput time (time from admission to discharge) for the telemedicine group was
      106 min; the average for the control group was 117 min. Telemedicine was found to
      be a satisfactory technique for pre-selected emergency department patients and
      was viewed by the physicians as an acceptable method of complementary care.

PMID- 9640722
TI  - Image selection in static telepathology through the Internet.
AB  - A telepathology study was carried out to examine the differences occurring when
      the images were selected by an experienced pathologist, a junior pathologist and
      a first-year resident. One hundred and fifty-five consecutive frozen-section
      pathology cases were collected and sent for consultation to a remote experienced
      pathologist using multimedia email. Local diagnoses (as reported in the files of
      the Institute, not from the image selector) and remote diagnoses (based on the
      images) were compared with those performed on paraffin-embedded sections.
      Acquisition time and number of selected images were recorded for each case and
      used to compare the different behaviour of the three local pathologists. Of the
      155 cases sent by telepathology, four were considered insufficient for a
      diagnosis by the remote pathologist and thus the diagnosis was postponed. In the
      remaining 151 cases, the overall diagnostic agreement between remote and
      definitive diagnosis was 96.7%. The results indicate that in the routine
      diagnostic work of a frozen-section service, an inexperienced pathologist can
      select images which are sufficiently informative for a remote diagnosis, in a
      sufficiently short time.

PMID- 9640723
TI  - Telematic electrodiagnosis from six laboratories in three European countries and
      one Asian country.
AB  - The results of an electrodiagnostic test, the electro-oculogram, recorded under
      standardized conditions, were compared. Recordings were obtained from 70 normal
      subjects in three European countries and 28 subjects in an Asian country. All
      subjects were 18-34 years old. Equal numbers of male and female patients were
      tested in each of six laboratories. There were no significant differences between
      the results of the European laboratories. There were, however, significant
      differences between the results of the European and the Asian laboratories, and
      between the results from the male and female subjects in all laboratories. This
      suggests the need for considering the possibility of male/female as well as local
      variations in normal control values when telemedicine is applied on a global
      scale.

PMID- 9640724
TI  - Portable satellite telemedicine in practice.
AB  - The US army's first portable telemedicine unit was built in 1993 and comprised a
      'ruggedized' videoconferencing unit. The unit was initially used in the United
      Nations' operations in Macedonia in February 1994 and subsequently in support of
      the Mobile Army Surgical Hospitals in Haiti, but its dimensions made it suitable
      only for locations where a move at short notice was unlikely. The second portable
      telemedicine unit comprised a PC linked to an Inmarsat B earth station through a
      modern. The unit allowed videoconferencing at 64 kbit/s. Three and a half years
      of clinical experience with both units has shown this to be quite adequate for
      the majority of clinical telemedicine. Portable telemedicine units have been a
      major benefit to medical commanders in the field.

PMID- 9640725
TI  - The development of a telemedicine laboratory as a medical faculty resource.
AB  - A telemedicine facility was established for the Faculty of Medicine of the
      University of Aberdeen and developed as a laboratory to help ensure a scientific
      approach to the implementation of telemedicine. Once a service application has
      been positively evaluated and established then it should be funded and delivered
      outside the laboratory, thus freeing up time and resources for the evaluation of
      new areas. Since it would appear that the practice of telemedicine is here to
      stay, it would also seem reasonable to suggest that an introduction to
      telemedicine should be included in the medical undergraduate curriculum.

PMID- 9640726
TI  - Teledermatology--high technology or not?
AB  - As an alternative to attending a conventional dermatology clinic, patients had a
      high-resolution conventional photographic image taken by a professional medical
      photographer. The photographic images were viewed by a dermatologist together
      with referral details from the general practitioner and any other relevant
      information from the patient's notes. From the images, a dermatological diagnosis
      was derived and a management plan for each patient instituted. After treatment,
      histological assessment of the tumours allowed diagnostic accuracy to be
      determined. The preliminary diagnostic accuracy (71%) was greater than that of
      the referring general practitioners (49%). However, when the diagnostic ability
      of the method to detect the nature of malignant lesions was examined,
      telemedicine was able to detect malignancies in 94% of cases compared with only
      70% detected by general practitioners. The results of the present study indicate
      that teledermatology is achievable using a low-technology, low-cost approach.

PMID- 9640727
TI  - Psychotherapy supervision conducted by videoconferencing: a qualitative study of
      users' experiences.
AB  - Psychiatry residents in Norway have 70 hours of mandatory psychotherapy
      supervision to develop insights into the therapeutic relationship. Six
      supervision pairs (six candidates and two supervisors) conducted five
      videoconferencing-based supervision sessions (384 kbit/s) and five face-to-face
      sessions alternating weekly for 10 sessions. Following completion of the 10
      sessions for candidates and supervisor B, and the 50 sessions for supervisor A,
      all subjects completed a semi-structured interview within two weeks. The eight
      subjects reported a wide range of experiences and attitudes. The results
      suggested that the quality of supervision can be satisfactorily maintained by
      using videoconferencing for up to half of the 70 hours required. The precondition
      for this estimate is that the pair in question have met face to face and
      established a relationship characterized by mutual trust and respect. Further
      studies, which include supervision pairs not having previously established
      relationships, are needed in order to indicate the generality of this
      precondition. The most obvious implication of this study is the potential for
      implementing decentralized models for recruiting and educating psychiatrists.

PMID- 9640728
TI  - The assessment of cognitive function in the elderly using videoconferencing.
AB  - People over the age of 65 were recruited from an inner-city old-age psychiatry
      service. Subjects had a structured interview (the CAMCOG test) by
      videoconferencing, and also face to face, by an investigator blind to the results
      of the test in the other mode. Reassessments were carried out within one week of
      the initial assessment. Eleven subjects were initially enrolled in the study and
      eight completed both modes. The number of patients in this study is very small
      but the results suggest that the CAMCOG test can be used reliably over a
      videoconferencing system without major modification.

PMID- 9640729
TI  - Use of video in the informed consent process.
AB  - We created a video-tape about the concept of telemedicine for informational and
      educational purposes. Two video-tapes, one with and one without the informed
      consent segment, were distributed to each of the Kentucky TeleCare sites. On the
      day of their teleconsultation, patients were asked to watch the video-tape (with
      the version containing the informed consent segment) before signing the informed
      consent to participate. Site coordinators then asked patients whether they had
      any specific questions about telemedicine. To date, patients have reported high
      levels of satisfaction with this method of consultation, using telecommunications
      technology to deliver health care.

PMID- 9640730
TI  - The Austrian Academic Computer Network and its usefulness for teleradiology.
AB  - To study the value of the Austrian Academic Computer Network (ACOnet) for
      teleradiology, 1740 test image data-sets and 620 image data-sets were exchanged
      between the departments of diagnostic radiology of the Universities of Innsbruck
      and Graz using the ACOnet service. Data transmission was reliable and fast with
      an average transfer capacity of 170 kByte/s (range 94-341). During the test
      phase, no major problems with image transfer occurred. Assuming that problems
      like security of patient data-sets, data compression and data verification can be
      solved, the ACOnet service would be a useful additional tool for telemedicine
      applications throughout Austria and eastern Europe.

PMID- 9640731
TI  - An Internet station for telemedicine in the Azerbaijan Republic.
AB  - We have established the first medical Internet and telemedicine station in the
      Azerbaijan Republic. The station began work on 16 June 1997. In the next three
      months a list of local and international medical electronic resources was drawn
      up and contacts made with medical informatics organizations and medical
      libraries. Five telemedicine consultations were carried out with Moscow clinics
      in specialties such as cardiology, ophthalmology, endocrinology and surgery. The
      quickest and most cost-effective way of improving medical care in Azerbaijan is
      to provide medical information support using modern telecommunications.

PMID- 9640732
TI  - Telemedicine and medical care to ships without a doctor on board.
AB  - Providing medical assistance to ships at sea was probably one of the first
      practical applications of telemedicine. At present, about 200 different
      organizations worldwide give medical assistance to ships without a doctor on
      board. The activity of the Foundation Centro Internazionale Radio Medico (CIRM),
      which probably has the largest experience in the world of telemedicine applied to
      seafarers, is reviewed. Medical assistance to seafarers has not improved in
      parallel with advances in medicine and telecommunications. Possible initiatives
      for improving teledelivery of medical assistance to seafarers are discussed.

PMID- 9640733
TI  - Value of a low-cost telemedicine link in the remote echocardiographic diagnosis
      of congenital heart defects.
AB  - We established a low-cost telemedicine link from a district general hospital to
      the regional paediatric cardiology department about 120 km away. The link was
      used to transmit echocardiographic images of newborn infants suspected of having
      congenital heart disease (CHD) to the referral centre, with simultaneous video
      and audio contact for consultation. Echocardiograms were transmitted for 61
      patients suspected of having CHD, aged from 1 to 42 days. The transmitted images
      were of adequate quality for the paediatric cardiologist to make a diagnosis in
      59 (97%). Congenital heart abnormalities were diagnosed in 38 (64%). Twelve
      patients (20%) had major CHD diagnosed on the transmitted scan and required
      transfer to the regional cardiology unit either urgently or electively after
      initial measures to stabilize the patient. Our findings suggest that, for babies
      suspected of having CHD, ultrasound images of diagnostic quality can be obtained
      and transmitted using a low-cost telemedicine system.

PMID- 9640734
TI  - Broadband multimedia for education.
AB  - Over the next five to ten years the accelerating development of computing and
      broadband networks will lead to a revolution in the ways in which health care is
      delivered. Patients will spend less time in the great institutions of the
      tertiary hospitals and the illnesses taking them there will assume a different
      pattern. The new information technologies will foster the emergence of general
      practices with a new emphasis on keeping patients in their communities for
      medical management. Knowledge exchange and delivery--to both patient and
      practitioner--will therefore become an increasingly important component of the
      health-care system in the next millennium.

PMID- 9640735
TI  - Nurse reactions to a prototype home telemedicine system.
AB  - We have studied nurse reactions to a prototype home health telemedicine system.
      The system used interactive video through the local cable television network. Six
      nurses were directly involved with telecare video-visits. There were 54 patients.
      The average age of the patients was 76 years (range 21-101). Thirty-six (67%)
      patients were female and 18 (33%) were male. The patients had an average of 4.6
      different diagnoses (range 1-16). They were also on a very wide range of
      medications (mean 9.9, range 2-23). Nurses overwhelmingly felt the system was
      effective for what this particular project was trying to accomplish. They were
      enthusiastic about the prospects of practising nursing by telemedicine, even
      though they had reservations about aspects of the particular system being used.
      Their main complaints were about limitations of the software and limitations of
      the telecommunication system that linked them to the patients.

PMID- 9640736
TI  - Cognitive behaviour therapy via interactive video.
AB  - Interactive video has been identified as a potential delivery medium for
      psychotherapy. Interactive video may restrict the range of both verbal and non
      verbal communication and consequently impede the development of a therapeutic
      relationship, thus influencing the process and outcome of therapy. A single case
      study explored the feasibility of the provision of congnitive behaviour therapy
      using interactive video with a client diagnosed as having mixed anxiety and
      depressive disorder. A range of outcome measures were included together with an
      independent psychiatric assessment prior to, and on completion of, therapy.
      Different levels of outcome were also examined: clinical, social, user views and
      administration. Outcome measures indicated a reduction in psychopathology and
      some modification of dysfunctional attitudes, with no apparent impairment of the
      working alliance.

PMID- 9640737
TI  - Practical evaluation of telemedicine systems in the real world.
AB  - There are six key questions that need to be asked before the evaluation of any
      telemedicine project. These are: who, why, what, when, where and how? Evaluation,
      and the subsequent communication of the results, is central to the development
      and implementation of any telemedicine system. As telemedicine technologies and
      processes gradually mature the extent and breadth of evaluations relevant to
      these technologies will undoubtedly improve and it is to be hoped that
      telemedicine systems will prove themselves as clinical tools.

PMID- 9640738
TI  - Hospice care using home-based telemedicine systems.
AB  - A pilot study of telenursing for terminally ill patients at home was launched as
      a collaborative effort between KUMC and the Kendallwood Hospice. The service used
      the public telephone network. Interactive video equipment was installed in the
      homes of three nurses who received after-hours calls and in the homes of six
      hospice patients living in either Kansas or Missouri. Data concerning the
      utilization patterns were gathered for two separate three-month periods. Patients
      and caregivers reported general satisfaction with the telehospice system. Both
      the nurses and social worker providers became comfortable about video-calls.
      Nurses conducted video-assessments to determine whether an 'in person' visit was
      necessary. This was particularly helpful for rural patients who were living a
      long way from the base station. In addition, Kendallwood serves an urban
      population and, in certain areas, night-time nursing visits raise safety
      concerns.

PMID- 9640739
TI  - A pan-European social alarm system.
AB  - SAFE 21 is a pan-European research and development project which will take social
      alarms into the twenty-first century. It is run by a consortium of eight
      organizations, with financial support from the European Commission. SAFE 21 will
      use existing infrastructure to deliver a much broader range of services and
      extend availability to users who are currently excluded. The project aims: to
      develop a social alarm that will work from anywhere inside the home, using a neck
      worn speech-pendant and outside the home making use of radio cellphone and global
      positioning technology; to demonstrate how telemedicine can be incorporated at
      marginal costs, by exploiting the existing social alarm infrastructure; to
      demonstrate a shared control centre that facilitates emergency services, medical,
      welfare and social professionals working together to support a broad-based social
      alarm system; to provide access to social alarms for deaf users, who are
      currently excluded.

PMID- 9640740
TI  - Telepsychiatry: an island pilot project.
AB  - A telemedicine link was established in 1996 between the island of Inishmore and
      the department of psychiatry in University College Hospital, Galway. The link was
      mainly used to facilitate emergency consultations between patients on the island
      and the duty psychiatrist, always at the request of the island's general
      practitioner. Nine patients were referred for assessment in this manner over
      eight months. Three patients had their first psychiatric contact and assessment
      through the video-link, and were followed up as outpatients via the link to
      eventual resolution of the episode of illness and discharge at the outpatient
      clinic. Our experience has been that videoconferencing systems are acceptable and
      satisfactory for patients and staff alike.

PMID- 9640741
TI  - The clinical and economic advantages of remote, community-based physiological
      assessment.
AB  - A prospective study documented the nutritional intakes of a large cohort of
      pregnant women living in Portsmouth and investigated the independent
      relationships of smoking, dietary intake and other maternal socio-economic
      factors on outcome and cardiorespiratory function of the child during sleep at
      home at three weeks and three months of age. Unattended overnight
      cardiorespiratory recording was performed and the data stored in local memory
      before transmission on demand via modem to Oxford next morning. The telemetry of
      the physiological data, entirely managed by part-time community nurses in
      Portsmouth, was very successful. Despite some losses, which included transmission
      failures, electrode or lead disconnection, and monitor malfunction, 92% of the
      physiological data were analysed at Oxford. Personalized physiological monitoring
      in the community provides an opportunity for new evidence bases that will enable
      a new level of individualized care.

PMID- 9640742
TI  - Cost evaluation of a telepsychiatry service in northern Queensland.
AB  - We conducted a simple comparison of the costs associated with delivering a mental
      health service by telepsychiatry and by conventional methods. The telepsychiatry
      rural outreach service was delivered to a mining town 900 km from the regional
      hospital in Townsville. When the telemedicine service was well established, 40
      cases a month were seen for general adult psychiatry, four for child and
      adolescent mental health, four for psychology and two for forensic services.
      Costs and quality-of-life issues were considered. The savings to the health
      authority were estimated to be $85,380 in the first year and $112,790 in
      subsequent years, not allowing for maintenance and equipment upgrading. We also
      estimated a 40% reduction in patient transfers due to the introduction of
      telemedicine. Based on the previous year's figures of 27 transfers at $8920 each,
      this would produce an annual saving of $96,336 for the Royal Flying Doctor
      Service. The results of the study showed considerable savings from reduced travel
      by patients and health-care workers.

PMID- 9640743
TI  - Teleradiology: results of a questionnaire of German radiologists.
AB  - A questionnaire was sent by mail to 4400 radiologists (i.e. to at least 1000
      radiological institutions). The response rate was about 5%. The results showed
      that 47% of respondents felt well informed about teleradiology, 49% not enough
      and 3% not at all. Image and report transfer as well as interfaces to reference
      databases, educational applications, technical quality surveillance and product
      support (maintenance) were considered to be increasingly important areas. Smaller
      institutions (1-3 doctors) judged expert consultation as more important than
      bigger institutions. Standardization, system stability and data security were
      demanded as well as guidelines, for example concerning the linking of report and
      image, correct documentation and required image quality. Technically most demands
      can be fulfilled today but this technology is not yet commonly included in
      teleradiology systems.

PMID- 9640744
TI  - The experience of the Royal Children's Hospital Mental Health Service
      videoconferencing project.
AB  - In April 1995 the Royal Children's Hospital Mental Health Service in Melbourne
      piloted the use of videoconferencing in providing access for rural service
      providers and their clients to specialist child and adolescent psychiatric input.
      What began as a pilot project has in two years become integrated into the service
      delivery system for rural Victoria. The experience of the service in piloting and
      integrating the use of videoconferencing to rural Victoria has been an important
      development for child and adolescent mental health services in Australia.

PMID- 9640745
TI  - Telemedicine applications in otolaryngology.
AB  - A prospective study of the use of realtime and store-and-forward teleconsulting
      was carried out in patients who presented to the New York Eye and Ear Infirmary
      for otolaryngology care. Forty-five patients were seen in the study. There were
      no significant differences between local and remote otolaryngologists when
      interpreting the examinations, indicating that transmission did not affect the
      ability of a qualified physician to make an accurate diagnosis. In the store-and
      forward examinations only 62% of the electronic records provided sufficient
      information for a confident diagnosis. Records were judged inadequate primarily
      due to poor selection, or an insufficient number of stored images. The study
      demonstrates that both interactive and store-and-forward techniques can be used
      to provide accurate clinical consultations in nasopharyngolaryngoscopic
      examinations. However, since store-and-forward consultations include less
      information and do not provide immediate feedback, as well defined clinical
      protocol for assembling the electronic consultation is needed.

PMID- 9640746
TI  - The International Telecommunication Union's report on Telemedicine and Developing
      Countries.
AB  - This paper reviews some of the main conclusions and recommendations from the
      Report on Telemedicine and Developing Countries, which was prepared for the
      International Telecommunication Union (ITU). The report is the result of three
      years' effort by a group of experts in telecommunications and telemedicine from
      around the world. It provides an extensive survey of the telemedicine experience
      of various countries. It discusses the different types and applications of
      telemedicine, the technologies used, costs and benefits, trends, prospects for
      global standards, and provides guidelines and recommendations to developing
      countries for implementation of telemedicine services. The ITU study group which
      prepared the report is expected to begin some new tasks in 1998, including the
      identification of a set of pilot telemedicine projects for developing countries.

PMID- 9640747
TI  - Design of mobile telemedicine systems using GSM and IS-54 cellular telephone
      standards.
AB  - This paper presents an overview of the design of mobile telemedical systems using
      cellular telephone channels. A mobile telemedicine communication system was
      studied using both the GSM and the IS-54 standards, which are the most widely
      used commercial cellular telephone systems in Europe and North America,
      respectively. A simulation using a photoplethesmography signal showed successful
      transmission of data with bit error rates of less than 10(-7) at the receiver for
      the IS-54 standard and less than 10(-5) for the GSM standard, depending on the
      mobile channel conditions used.

PMID- 9640748
TI  - A joint US-UK study of home telenursing.
AB  - Nursing notes for patients nursed at home in the USA and the UK were reviewed
      using an abstraction instrument developed and tested in the US. More than 1700
      episodes of patient care at home were reviewed: 906 in the US and 839 in the UK.
      Preliminary data suggest that in the US approximately 45% of home nursing visits
      could be done via telemedicine, while the figure is lower in the UK, less than
      15%. Pilot trials of an analogue video-telephone in Kansas City and Belfast
      suggest that even relatively low-quality compressed video may be useful for home
      nursing. Clearly, there are differences between the two countries which merit
      further study, but there is evidence to suggest that telemedicine may have a role
      in the delivery of home health care.

PMID- 9640749
TI  - Feasibility of orthopaedic teleconsulting in a geriatric rehabilitation service.
AB  - Fifteen elderly patients participated in a teleconsultation with an orthopaedic
      surgeon, which was then followed by a conventional, face-to-face consultation.
      The comparison between the surgeon's ratings for both types of consultation
      suggested that the telemedicine consultation was satisfactory in terms of the
      quality of image and sound, the clinical examination and general simplicity. The
      telemedicine consultations did not generate a need for any additional clinical
      investigations, although in two cases a face-to-face consultation was necessary
      to clarify clinical signs (shortening of a limb and scar tissue). The surgeon's
      rating of his decision level was superior in the face-to-face situation in four
      cases, and for 11 patients it was equal. Similarly, the surgeon's level of
      confidence in decision making was superior in the conventional situation for five
      patients and equal for 10 patients. Patient attitudes towards teleconsulting were
      favourable. There was a high level of patient satisfaction. Teleconsulting
      between orthopaedic surgeons and elderly patients therefore appears to be
      possible, provided that certain technical, clinical and psychological
      considerations are addressed.

PMID- 9640750
TI  - Continuous assessment of the risk of falling using telecare.
AB  - The prevention of falls in the elderly could be based on risk assessment and the
      prediction of when an individual is likely to sustain an injury. A telecare
      system should allow the dynamic assessment of risk to be produced by a control
      centre computer, based on data transmitted from local sensors in the elderly
      person's home. A fall risk index could be calculated from mobility, activities of
      daily living and medication. However, substantial data-sets will be required
      before such fall risk indices attain statistical significance. As they are
      developed, fall prediction algorithms could be constantly reviewed and modified
      in order to reach the point where an acceptable level of accuracy is reached.

PMID- 9640751
TI  - Benefits of using telemedicine and first results in Bosnia and Herzegovina.
AB  - In October 1996 the Institute of Pathology with the Radiology and Ophthalmology
      Clinic of the university hospital of Sarajevo joined the experimental
      telemedicine project SHARED. Two months after the project began, dermatology,
      paediatrics and haematology were also included. During the first phase we had 40
      teleconsultations that showed us the benefits of using telemedicine. Our opinions
      and the opinions of the pathologist in Milan were similar for most of the
      biopsies (78%). The total time required for the consultation for the first 40
      cases was 372 min, or 9.3 min each, on average. The longest consultation time was
      25 min. The largest number of images was 44 per case, the smallest four. Because
      of problems of infrastructure and lack of experts, telemedicine will be important
      to a small country like Bosnia and Herzegovina.

PMID- 9640752
TI  - Easy Medic: an Internet application for the general practitioner.
AB  - A research project has been carried out to develop a client server application
      which supplies the general practitioner (GP) with a 'personal digital assistant'
      (hand-held mobile computer) to connect to Web servers at a hospital site through
      the Internet. This allows the doctor to book medical examinations, hospital
      admissions and manage patient data. The application used advanced object-oriented
      techniques, on both the client and the server side. The connection to a Web
      server was achieved through GSM wireless cellular telephones using standard
      Internet protocols (HTTP, TCP/IP and CGI). Conventional telephone lines can be
      used as well. Other application modules on the client side provided patients
      medical record supervision, GP schedule management, general information about
      hospitals and clinics, and pharmacy consultation. These services should help GPs
      in their daily work. Moreover, the quality of health-care resource management and
      cost supervision should improve, since each GP 'transaction' is automatically
      entered in realtime into a database at the server. The services are under test in
      the health-care system of an urban area in southern Italy.

PMID- 9640753
TI  - The legal and ethical aspects of telemedicine.
AB  - The medical challenge presented by telemedicine is for doctors to find
      satisfactory ways of doing their jobs from a distance. The legal and ethical
      challenge presented by telemedicine is to ensure that the very highest standards
      are met from the outset. This can be achieved only by the legal and medical
      professions learning to combine their expertise, rather than by the former
      adopting the adversarial stance that has come to punctuate its relationship with
      the latter in recent years.

PMID- 9640754
TI  - The use of telemedicine to treat ophthalmological emergencies in rural Australia.
AB  - A retrospective analysis was made of a cohort of patients who presented
      sequentially with acute ophthalmological conditions which were managed by
      telemedicine consultation. Twenty-four patients presented with acute problems
      requiring specialist ophthalmological advice to the emergency department of a
      remote hospital in Mt Isa, Queensland, between December 1996 and February 1997.
      Tele-ophthalmology consultations were carried out with three ophthalmologists
      working in a specialist eye clinic in Townsville, 900 km away. Patients and
      doctors were extremely positive about the telemedicine facility. Tele
      ophthalmology was an effective means of providing acute specialist consultation
      in a remote emergency department. By reducing the need for acute transfers to the
      tertiary hospital in Townsville, significant benefits can be anticipated--both
      financial and in terms of convenience for the patient. Benefits for medical staff
      in skills acquisition and education were also evident.

PMID- 9640755
TI  - A survey of physicians' acceptance of telemedicine.
AB  - Physicians' acceptance of telemedicine is an important managerial issue facing
      health-care organizations that have adopted, or are about to adopt, telemedicine.
      Most previous investigations of the acceptance of telemedicine have lacked
      theoretical foundation and been of limited scope. We examined technology
      acceptance and usage among physicians and specialists from 49 clinical
      departments at eight public tertiary hospitals in Hong Kong. Out of the 1021
      questionnaires distributed, 310 were completed and returned, a 30% response rate.
      The preliminary findings suggested that use of telemedicine among clinicians in
      Hong Kong was moderate. While 18% of the respondents were using some form of
      telemedicine for patient care and management, it accounted for only 6.3% of the
      services provided. The intensity of their technology usage was also low,
      accounting for only 6.8% of a typical telemedicine-assisted service. These
      preliminary findings have managerial implications.

PMID- 9640756
TI  - [Effects of coca chewing on the glucose tolerance test].
AB  - The effects of coca chewing on the glucose tolerance test were measured. The
      subjects were 14 habitual coca chewers and 14 non-chewers. All were of Aymara
      ancestry and came from a rural community from the "Altiplano" close to the city
      of La Paz. The coca users chewed coca leaves during 3 1/2 hours of the test. The
      non-chewers showed a significant hypoglycemia at 120 minutes of the test. This
      effect was not observed in the coca chewers. The hormonal counter-regulation
      response to hypoglycemia worked perfectly in non-chewers, since glucose levels
      reached normal values at 180 minutes of the test. These results suggest that coca
      chewers, at high altitude do not present hypoglycemia, due to an antagonic action
      of coca metabolites on insulin; allowing a greater availability of glucose in the
      organism. This would have a positive effect on metabolism in an environment of
      hypobaric hypoxia, known to lead to situations of hypoglycemia.

PMID- 9640757
TI  - Medical informatics in perinatology project AGUSTINA in Argentina.
AB  - This paper reviews the development of the field of medical informatics in Latin
      America. It also describes the preliminary results of a computer-based data
      management system, named AGUSTINA, which is comprised of maternal and infant data
      on 6195 deliveries that occurred between June 1990 and December 1995 in a
      hospital in the surroundings of Buenos Aires, Argentina. These data were
      fundamental for the instrumentation of preventive community-oriented activities
      in the area. Finally, this paper describes recommendations for future actions in
      the area of medical informatics in Latin America.

PMID- 9640758
TI  - Lower motor neuron syndrome associated with anti-GM1 antibodies.
AB  - It has been recently recognized that increased titers of serum anti-GM1
      antibodies may be associated with motoneurone diseases or with multiple motor
      neuropathy with or without conduction block and also with chronic sensorimotor
      neuropathy and Guillain-Barre syndrome. Santoro et al. were the first to note
      that anti-GM1 antibodies were able to bind to the nodes of Ranvier of the sural
      nerve of a patient with clinical signs and symptoms mostly resembling amyotrophic
      lateral sclerosis who also showed, in nerve conduction studies, multifocal motor
      nerve fibers conduction block and serum IGM anti-GM1 antibodies. The two patients
      presented in this report had asymetrical motor neurone disease with signs and
      symptoms of lower motoneurone involvement, and other signs, in the first patient,
      which suggested the existence of upper motoneurone damage. Besides, the second
      patient also had clinical sensory impairment in the lower limbs.
      Electrophysiologically, none of them had nerve conduction block but both showed
      inexcitable median and sural nerve sensory fibers. Both had high titers of anti
      GM1. A sural biopsy of both patients showed immunoglobulins into the sensory
      fibers. However, we do not know whether the anti-GM1 antibodies bind to a cross
      reactive glycolipid other than the GM1 itself. In any case, it seems that the
      presence of anti-GM1 antibodies might be a marker signalling a potentially
      treatable immune disorder which may have signs of lower and upper motor neurone
      disease and, also, clinical and electrophysiological evidences of peripheral
      sensory involvement.

PMID- 9640759
TI  - [Changes in the levels of delta-aminolevulinic acid dehydratase in chronic
      alcoholic patients].
AB  - Medical and biochemical analysis were performed on 58 patients with chronic
      alcoholism. In accordance with medical characterisation, patients were divided in
      three groups: A (patients having only hepatopathy), B (patients with hepatopathy
      and neuropathy) and C (patients having only alcoholic neuropathy).
      Simultaneously, several parameters related to heme biosynthesis were examined.
      Urinary delta-aminolevulic acid (ALA), porphobilinogen (PBG) and porphyrins and
      fecal porphyrins measurements did not show significant difference among all
      studied groups. The activities of ALA-dehydratase (ALA-D), uroporphyrinogen-I
      synthase (URO-I-S) and uroporphyrinogen-III-synthase (URO-III-S) were monitored
      in peripheral erythrocytes. From the enzymes measured, only ALA-D levels in
      groups B and C were significantly depressed (p < 0.002) compared with normal
      subjects. The decrease in ALA-D correlated with the degree of neuropathy.

PMID- 9640760
TI  - [Community-acquired Staphylococcus aureus bacteremia in children: analysis of
      mortality risk factors].
AB  - Sixty episodes of community-acquired Staphylococcus aureus bacteremia (SaCB) were
      prospectively analyzed between January 1990 and December 1994. The mean age of
      the patients was 78 (1-180) months. Thirteen (55%) of the children had underlying
      disease, the most frequent one being acute lymphoblastic leukemia. In 83% of the
      episodes a primary site of infection was observed. Skin and osteoarticular foci
      were the most frequently encountered. Only two patients had endocarditis.
      Arterial hypotension was detected in 17% of the patients. Ninety two percent of
      S. aureus isolated were penicillin-resistant. Only two strains were methicillin
      resistant. In 24 (40%) episodes where metastatic foci were detected,
      osteoarticular infections were predominant. Mortality due to SaCB was 20%.
      Multivariate analysis by logistic regression revealed that arterial hypotension
      (RR = 24.8; 4.77-128.9), leucopenia (RR = 10.3; 1.25-86.2) and non hemato
      oncologic diseases (RR = 10.0; 1.09-92.2) correlated with high mortality rate (p
      = < 0.001).

PMID- 9640762
TI  - [Anti-neutrophil cytoplasmic antibodies (ANCA) in patients with symptomatic and
      asymptomatic HIV infection].
AB  - The cytopathic effect of HIV on CD4 T cells, as well as the active autoimmune
      mechanism occurring during infection, have been documented. Of the cytokines
      involved in the pathogenesis of AIDS, the main one produced by the monocyte
      macrophage series is tumor necrosis factor alfa (TNF alpha). This cytokine
      induces antigens such as proteinase 3 (Pr 3) or mieloperoxidase (MPO). Anti
      neutrophil cytoplasmic antibodies (ANCA) are directed against this type of PMN
      antigens. In the present paper, the role of anti-neutrophil cytoplasmic
      antibodies (ANCA) in HIV infected patients as responsible for autoimmune
      phenomena in relation to opportunistic infections, was studied. A total of 88
      serum samples belonging to 49 asymptomatic and 39 symptomatic HIV infected
      patients were tested for ANCA by an indirect immunofluorescence (IIF) test over a
      neutrophil substrate. ANCA were detected in 53.8% of symptomatic patients as
      compared to 4.1% in asymptomatic cases (p < 0.0001). A 95.9% correlation was
      observed between ANCA-positive samples and pulmonary infection (n = 20). In those
      ANCA (+) samples 95.9% correlation was found with pulmonary infection (n = 20).
      Pulmonary infection due to Mycobacterium tuberculosis is a frequent finding in
      HIV infected patients from Northeastern Argentina. When the presence of ANCA in
      TB(+) HIV(+) and TB(+) HIV(-) patients was studied, it was seen that positive
      ANCA significantly correlated with the first group (p < 0.001). The presence of
      ANCA was not related to viral infections, toxoplasmosis, neurological features of
      AIDS, vasculitis or malignant diseases. ANCA during pulmonary infection, mostly
      caused by TB, as well as PMN infiltration in pulmonary parenchyma, and the
      deregulated immune reaction elicited by HIV, may contribute to the onset of
      autoimmune phenomena. The presence of human T lymphocytes reactive to heat stress
      proteins (Hsp), an important target of immune response against certain
      intracellular auto-antigens such as MPO from PMN, added to the mechanism of
      molecular mimicry, could explain the association of ANCA and TB in patients with
      severe alterations of their immune response. According to these results, the
      limited presence of ANCA in asymptomatic patients HIV(+) and in HIV(-) with
      pulmonar TB, could indicate that the virus may not be responsible for the
      induction of these antibodies.

PMID- 9640761
TI  - [Prevalence of hepatitis C antibodies in plasma donors for the treatment of
      Argentine hemorrhagic fever].
AB  - For Argentine Hemorrhagic Fever, a disease caused by Junin virus (JV), there is
      an effective treatment, consisting of the transfusion of immune plasma (IP). This
      plasma is obtained from individuals who have had the disease. Since Hepatitis C
      virus (HCV) is transmitted parenterally, this study was aimed to estimate the
      prevalence of anti-HCV in a population of IP donors. In this study, 376 donors
      (47 females and 329 males) were studied: 95 individuals (24 females and 71 males)
      who had had FHA but had not received treatment and 88 laboratory workers (57
      females and 31 males) who were included as controls. Serum samples were tested by
      EIA (Abbott, Germany) for HCV, and later confirmed by LIATEK (Organon, Ireland).
      Antibodies to HCV were detected in 29/376 donors (7.7%), in only 1/95 (1.0%)
      untreated convalescents of AHF and in 1/ 88 (1.1%) of laboratory workers.
      Retrospective analysis of the seroconversion for HCV in these individuals
      demonstrated that in 16/24 donors (66.6%) the infection by HCV was probably
      associated with the IP transfusion. The data presented herein show how the
      infection with HCV was disseminated among donors of IP, stressing the risk
      associated to transfusional practices, and emphasizing the need of vaccination to
      prevent AHF and also the risk inherent to its treatment.

PMID- 9640763
TI  - [In vitro study of hemopoietic progenitors in human umbilical cord blood treated
      with different cytokines and autologous serum].
AB  - The aim was to obtain the ex vivo expansion of human umbilical cord blood (HUCB)
      cells. A total of 19 samples were assayed to evaluate the number and type of
      hemopoietic progenitor cells, their proliferating capacity and the stimulating
      potency of cord blood serum. METHODS: a) CFU-GM, CFU-GEMM and BFU-E cultures in
      the presence of CSF, BM serum or HUCB serum; b) 35 day LTC in liquid media
      whether in presence of IL-3 + GM-CSF + SCF or autologous serum (AS). Cells were
      demidepopulated at 7-day intervals and fresh medium and cytokines were added.
      Harvested cells were cultured in bone marrow (BM)/ SM and colonies were evaluated
      after 10 days. RESULTS: The mean number of CFU-GM was similar to BM values; the
      maximum number of colonies was observed at day 7 and remained high until day 21
      whether in addition of cytokines or AS. A total of 8 samples gave rise to
      colonies up to day 35; these samples showed higher values than BM in SM; HUCB
      serum has a great stimulating effect on BM cells and HUCB cells compared with
      nonspecific stimulating factors; moreover, HUCB showed a large dispersion.
      CONCLUSION: 1) HUCB contains a high number of hemopoietic progenitor cells with a
      large dispersion coefficient, 2) HUCB plasma has a great stimulatory capacity, 3)
      it is possible to induce the expansion of HUCB progenitors in LTC either in the
      presence of cytokines or of AS without loss of potency.

PMID- 9640764
TI  - [Essential fatty acids of the n-6 and n-3 series supplied to human diet by edible
      fish from the Parana river].
AB  - The fatty acid composition of muscle lipids from eadible fish from Parana river
      such as Dorado (Salminus maxillosus), Boga (Leporinus affinis), Pati
      (Luciopimelodus pati) and Surubi (Pseudoplatistoma coruscans) was studied in
      order to determine their food value in relation to essential fatty acid n-3 and n
      6 supply. Flesh from these fishes is relatively lean and its lipids only contain
      35% to 38% saturated fatty acids. Significant amounts of n-6 polyethylenic acids,
      mainly linoleic, arachidonic and the n-3 acids, docosahexaenoic,
      docosapentaenoic, eicosapentaenoic and alpha-linolenic are found in these fishes.
      Pati flesh is the most abundant in n-6 acids with a value of 306 mg/100 g muscle,
      followed by Boga, Dorado and Surubi. A large proportion of n-3 acids is supplied
      by muscles of Dorado, 183 mg/100g muscle, followed by Pati, Boga and Surubi. More
      than 90% of the lipids that supply these acids are present in triacylglycerols in
      Dorado, Boga and Pati. In Surubi, triacylglycerols constitute 60% and the
      remaining lipids are phospholipids. Cholesterol content in flesh of fresh water
      fish was analyzed, and it did not exceed 4.7 micrograms/g muscle for Pati, being
      lower for the other species studied. Fish considered in this work represent a
      good dietary source of polyunsaturated fatty acids either n-6 or n-3 series for
      the mediterranean population in our country.

PMID- 9640765
TI  - [Action of liver extract from partially hepatectomized mice on the mitotic
      activity of young mouse enterocytes].
AB  - We have previously demonstrated that adult mouse plasma obtained 36 hours post
      partial hepatectomy has an inhibitory effect on the mitotic activity of
      enterocytes from young mouse duodenal cripts. In this paper we investigate
      whether this effect is derived from any regenerating liver factor. Accordingly,
      we studied the action of adult mouse (90 days old) liver extract obtained 36
      hours after partial hepatectomy (70%), on the mitotic activity of young mouse
      enterocytes, considering 3 cellular levels of the duodenum cripts. Thirty six
      C3H/S inbred female mice (27 days old) were employed. Half of them received at
      16:00 hour an intraperitoneal injection of saline and the other half received
      liver extract (0.01 ml/g). Animals from each group were sacrificed at 08:00/ 16,
      12:00/20 and 16:00/24 (time of day/hours post treatment). All the animals
      received an intraperitoneal dose of colchicine (2 micrograms/g) 4 hours before
      sacrifice. The results are expressed as colchicine metaphases/1000 nuclei and
      show that the mitotic activity is significantly lower in the animals treated with
      the extract than in the controls. This inhibiting effect is observed at the
      levels from 1 to 4 and from 5 to 12 cells of the analyzed cripts. At the
      superficial level from 13 to 20 cells there is no modification of the
      proliferative activity. This inhibiting effect on the mitotic activity of
      duodenum enterocytes from the basal and intermedial zone of the cripts is
      probably due to a liver diffusing factor.

PMID- 9640766
TI  - [Cardiac failure secondary to hypoparathyroidism. An unusual presentation].
AB  - The case of a 37 year old woman with hypoparathyroid congestive heart failure
      (CHF) is reported. Thyroidectomy had been performed eight years earlier and she
      had experienced symptoms of hypocalcemia postoperatively. CHF improved rapidly
      and completely with the treatment of hypocalcemia. Good prognosis is emphasized
      but it is necessary to think about this cause of ventricular dysfunction in a
      patient with CHF and a history of neck surgery in order to make an early
      diagnosis. Pathogenic mechanisms and differential diagnosis are discussed.

PMID- 9640767
TI  - [Large granular lymphocytic leukemia. Case report with scarce expression in
      peripheral blood].
AB  - The case of a 33 year old woman with a large granular lymphocytic leukemia is
      presented. The main symptoms were neutropenia and recurrent respiratory bacterial
      infections. No enlargement of the liver, spleen or lymph nodes was noted.
      Circulating lymphocytes averaged 3000/microliter with 35% of large granular
      cells. The bone marrow biopsy showed lymphatic infiltration with both nodular and
      interstitial pattern. Lymphocytes bore the T suppressor phenotype (CD8+, CD45
      RO+, CD20-, kappa-, lambda-). Cytogenetic studies revealed a low expression clone
      with 7q-: del (7)(q36). Gene rearrangements for immunoglobulins or T-cell
      receptors could not be demonstrated by Southern Blot. Bone marrow cultures grew
      normally while both normal and patient bone marrow showed marked inhibition when
      incubated with patients serum. Normalization of the peripheral granulocytic count
      was obtained with prednisone, while granulocytic-stimulating factors,
      chlorambucil, and cyclosporine A were partially active or inactive. We suggest
      that this case represents a form of the lymphoproliferative disease of granular
      lymphocytes. To our knowledge, the deletion of the long arm of chromosome 7 has
      not been described in this disease.

PMID- 9640768
TI  - [Superantigens and retroviral infections. Increase of mammary tumorigenicity due
      to recombination between exogenous and endogenous MMTV viruses].
AB  - A number of milk-borne exogenous mouse mammary tumor viruses (MMTV) infect mice
      shortly after birth and, when expressed, produce superantigens. Herein we
      describe the biological effects of new variants of exogenous MMTV: one of them
      (BALB14) present in BALB/c mice and showing a low ability to induce mammary
      tumors, and the other (MMTV-7) being the result of recombination between the
      BALB14 and the Mtv-7 endogenous provirus. The recombinant virus which has the SAg
      specificity of Mtv-7 was amplified in BALB/c mice this fact correlating with a
      high incidence of mammary tumors. The role of strong SAgs in the mechanism by
      which the recombinant virus increases its title in a susceptible host is
      discussed. The results obtained suggest that the presence of non-productive
      endogenous proviruses--considered as conferring a selective advantage to the
      mouse population by protecting it from infection with exogenous MMTV--should also
      be advantageous to the pathogen by increasing its variability, thus broadening
      the host range and allowing the expansion of highly tumorigenic variants.

PMID- 9640769
TI  - [Role of different forms of fibronectin in in vitro bovine follicular
      development].
AB  - This study was aimed at testing the hypothesis that different forms of
      fibronectin (FN), produced as a consequence of the alternative splicing of the
      precursor mRNA, play specific roles during follicular development. In particular,
      we analyzed the presence of the ED-I region, which is absent in the plasma form.
      Analysis of FN levels in follicular fluids corresponding to different stages of
      development of bovine follicles revealed marked changes in the concentrations of
      ED-I + FN whereas total FN levels remained relatively constant. A negative
      correlation (P < 0.001) was detected between ED-I + FN and estradiol levels. This
      steroid was without effect on the alternative splicing of FN in primary cultures
      of bovine granulosa cells. However, cAMP produced a marked decrease in the
      incorporation of the ED-I region. In contrast, transforming growth factor beta
      (TGF-beta) elicited both a stimulation on overall FN synthesis and an increase in
      the inclusion of ED-I. This effect was evident at the protein level (Western
      blots) and also in the mRNAs (Northern blots). A peptide corresponding to the ED
      I region stimulated DNA synthesis in a bovine granulosa cell line (BGC-1) whereas
      the peptide corresponding to the flanking sequences was without effect. Data
      presented herein suggest a novel form of regulation by which changes in the
      primary structure of FN may mediate some of the effects of gonadotropin and
      intraovarian factors during follicular development.

PMID- 9640770
TI  - [Regulation of testicular steroidogenesis by nitric oxide].
AB  - Testicular macrophages as well as endothelial cells, which are intimately
      associated with Leydig cells, constitute a potential source of paracrine nitric
      oxide (NO). In the present study, we investigated the effect of NO donors on MA
      10 murine Leydig tumor cell line and rat Leydig cell steroidogenesis. We observed
      that NO donors, reversibly inhibit hCG-induced steroidogenesis in both types of
      cells. We also studied NO mechanism of action. Contrary to what is observed in
      many other systems, NO inhibitory effect on Leydig cell steroidogenesis is not
      mediated by cGMP, as NO fails to increase cGMP production and cGMP analogs do not
      reproduce NO effect. NO does not modify the production of cAMP, the main second
      messenger that mediates gonadotropin action. When we studied NO effect over the
      steroidogenic pathway in MA-10 cells, we found that NO is inhibiting the
      conversion of cholesterol to pregnenolone. Taken together these results show an
      inhibitory effect of NO donors on Leydig cell steroidogenesis and suggest that NO
      can be directly inhibiting cholesterol side-chain cleavage enzyme (cytochrome P
      450 scc) as it does with other heme proteins, including different cytochromes P
      450.

PMID- 9640771
TI  - [Community-acquired pneumonia in adults. Clinical practice guideline for
      Argentina. Study Group on Community Acquired Pneumonia].
AB  - Community-acquired pneumonia (CAP) affects approximately 1% of the population
      annually. Initial antimicrobial therapy is most often empirical. Guidelines
      designed in other countries for the empirical management of CAP are not
      recommended for use in Argentina. Studies from other countries were considered
      together with unpublished local data to define the potential etiologic
      microorganisms and their antimicrobial susceptibility. Recommended diagnostic
      tests, groups of patients for different therapies and hospitalization criteria
      were defined. Severe CAP requiring intensive care was distinguished from the rest
      because of its distinct spectrum of etiologic agents and its high mortality,
      requiring a more focused therapy. Age, coexisting conditions and severity of
      illness were taken into account in the election of therapy.

PMID- 9640772
TI  - [Heart failure and dysautonomia in a hemodialyzed patient].

PMID- 9640773
TI  - [Kaposi sarcoma after renal transplantation].

PMID- 9640774
TI  - [Nuclear transfer and cloning].

PMID- 9640775
TI  - [Thymectomy and myasthenia gravis].

PMID- 9640776
TI  - [Exercise and sudden death. Is it possible to prevent it?].

PMID- 9640777
TI  - [Acute effect of lorazepam on respiratory muscles in patients with chronic
      obstructive pulmonary disease].

PMID- 9640778
TI  - [Exogenous gangliosides and Guillain-Barre syndrome].

PMID- 9640779
TI  - Genomic characterization of adenovirus serotype 7 isolated in Brazil from acute
      respiratory disease patients during the period from 1980 to 1991.
AB  - Forty isolates of adenovirus type 7 were analized by restriction enzyme digestion
      with BamHI, SmaI, EcoRI and HindIII. These isolates were obtained from acute
      respiratory disease patients during the years 1980 to 1991. Only two genomic
      types were found: Ad7b and Ad7e, with Ad7b (87.5%) being more frequent than Ad7e
      (12.5%). The genomic type Ad7e appeared in the years 1980, 1981 and 1983. Ad7b
      appeared in 1982 and it was the only genomic type found from 1984 to 1991. Both
      genomic types were responsible for lower (LRTI) and upper (URTI) respiratory
      tract infection, but the proportion LRTI/URTI is higher for Ad7b (25/6) than for
      Ad7e (1/4).

PMID- 9640780
TI  - Hantavirus pulmonary syndrome in the Province of Rio Negro, Argentina, 1993-1996.
AB  - Early in 1995 the first case of Hantavirus Pulmonary Syndrome was serologically
      confirmed in El Bolson (Province of Rio Negro, Argentina), corresponding to the
      third outbreak reported in Argentina. A total of 26 cases of HPS related to the
      Andean region of Rio Negro Province, were reported from 1993 to 1996, 17 in El
      Bolson, 4 in San Carlos de Bariloche, and 5 in Buenos Aires. The incidence rate
      was 5.03 x 100,000 with a mortality rate of 51.85 x 100. The occurrence of cases
      was mainly seasonal, with a significantly greater number in the spring, and the
      persons affected mainly lived in urban or periurban areas. In four cases, the
      affected individuals were members of a couple, spouses or live-in contacts. Seven
      cases were Health workers (physicians, nurses or administrative staff). Twelve
      cases were related among them, due to an outbreak of 80 days. Two of them did not
      visit the Andean region. A total of 139 rodents were captured and seven of them,
      Olygoryzomys longicaudatus, were found to be serologically positive. The
      possibility of infection by contact with rodents or fecal matter is being
      analyzed and also hypothesis related with interhuman transmission.

PMID- 9640781
TI  - Quantification of the population and phagocytary activity of hemocytes of
      resistant and susceptible strains of Biomphalaria glabrata and Biomphalaria
      tenagophila infected with Schistosoma mansoni.
AB  - Among the determinant factors in the resistance and susceptibility of
      Biomphalaria to Schistosoma mansoni, hemocytes play an important role. Aiming at
      studying S. mansoni/Biomphalaria interactions related to hemocytes, the first
      step is certainly connected with the standardization of this cell population in
      uninfected Biomphalaria. In this way, quantification of this cell population in
      hemolymph, as well as its phagocitary capacity, have been determined for the
      first time. Furthermore, using susceptible and resistant strains of B. glabrata
      and B. tenagophila, the hemocytegram and phagocytary capacity of hemocytes after
      infection with S. mansoni were determined too. Resistant and susceptible strains
      of B. glabrata (BA and BH, respectively), as well as resistant and susceptible
      strains of B. tenagophila (TAIM and CF, respectively) were infected with 10
      miracidia of the LE and SJ strains of S. mansoni, respectively. These infected
      snails and respective uninfected controls were assessed in relation to the number
      of circulating hemocytes and alteration in the phagocytary capacity, by using
      Zymozan and MTT. Reading was taken by means of a spectrophotometer at 5 hours and
      1, 2, 5, 10, 20 and 30 days after infection. The results showed a decrease in
      population of the circulating phagocytary cells, 5 hours after infection. One day
      post-infection, the circulating cells of the susceptible snails showed an
      increased metabolic activity, but the same event could not be observed in the
      resistant strains. In the subsequent observation periods, significant differences
      among the strains studied could not be observed until the end of the experiment.

PMID- 9640782
TI  - Differentiation of pathogenic and non-pathogenic leptospires by means of the
      polymerase chain reaction.
AB  - A polymerase chain reaction was carried out to detect pathogenic leptospires
      isolated from animals and humans in Argentina. A double set of primers (G1/G2,
      B64-I/B64-II), described before, were used to amplify by PCR a DNA fragment from
      serogroups belonging to Leptospira interrogans but did not allow to detect
      saprophytic strains isolated from soil and water (L. biflexa). This fact
      represents an advantage since it makes possible the differentiation of pathogenic
      from non-pathogenic leptospires in cultures. The sensitivity of this assay has
      been determined, allowing to detect just only 10 leptospires in the reaction
      tube. Those sets of primers generated either a 285 bp or 360 bp fragment,
      depending on the pathogenic strain.

PMID- 9640783
TI  - Peptic disease and Helicobacter pylori are highly prevalent in patients with the
      indeterminate form of Chagas' disease: report of 21 cases.
AB  - Given that chagasic patients in the indeterminate form of this disease, can have
      abnormal motility of the digestive tract and immunologic abnormalities, we
      decided to assess the frequency of peptic disease and Helicobacter pylori (Hp)
      infection in these individuals. Twenty-one individuals, 13 males and 8 females,
      mean age 37.6 +/- 11.1 years, were examined. Biopsies of the duodenum, antrum,
      lesser and greater gastric curvature and esophagus were performed. The endoscopic
      findings were of chronic gastritis in 20 (95.2%) patients, duodenal ulcer in 3
      (14.3%), gastric and duodenal ulcer in 3 (14.3%), gastric ulcer alone in 1
      (4.8%), esophagitis in 5 (23.8%), and duodenitis in 5 (23.8%). The diagnosis of
      infection by the Hp was done by the urease test and histologic examination. Hp
      infection was found in 20 (95.2%) individuals: in 20 out of them in the antrum,
      in 17 in the lesser curvature, and in 17 in the greater curvature. Hp was not
      found in the esophagus and duodenum. The only individual with no evidence of
      infection by Hp was also the only one with normal endoscopic and histologic
      examinations. The histologic examinations confirmed the diagnoses of gastric
      ulcer as peptic, chronic gastritis in 20 patients, duodenitis in 14, and
      esophagitis in 9. In this series the patients had a high frequency of peptic
      disease, which was closely associated with Hp infection.

PMID- 9640784
TI  - Prevalence of HTLV-I and HTLV-II infections among HIV-1-infected asymptomatic
      individuals in Sao Paulo, Brazil.
AB  - Human immunodeficiency virus (HIV-1)-infected subjects with acquired
      immunodeficiency syndrome (AIDS) are often infected with multiple pathogens. In
      particular, HTLV-I and HTLV-II infections have been found more frequently in AIDS
      patients than in asymptomatic individuals in Europe and Japan. We carried out a
      serosurvey among asymptomatic HIV-1-infected subjects in Sao Paulo, Brazil and
      compared our results with those of other investigators. In this study, we found
      HTLV infection in 1.5% of 266 asymptomatic and 14% of 28 AIDS patients.
      Epidemiological data obtained from patients pointed out the use of intravenous
      drugs as the principal risk factor for acquiring retroviruses. In conclusion, our
      results are in accordance with other studies done in Brazil and elsewhere where
      the principal risk group for HIV/HTLV-I/II coinfection was IDU.

PMID- 9640785
TI  - Agreement between premortem and postmortem diagnoses in patients with acquired
      immunodeficiency syndrome observed at a Brazilian teaching hospital.
AB  - Acquired immunodeficiency syndrome (AIDS) is one of the main causes of death in
      adults worldwide. More commonly than in the general population, in patients with
      AIDS there is substantial disagreement between causes of death which are
      clinically suspected and those established by postmortem examination. The
      findings of 52 postmortem examinations were compared to the premortem (clinical)
      diagnoses, and there was 46% agreement between them. Fifty two percent of the
      patients had more than one postmortem diagnosis, and 48% had at least one AIDS
      related disease not suspected clinically. Cytomegalovirus infection was the
      commonest (30.7%) autopsy finding, but not a single case had been suspected
      premortem. Bacterial infection, tuberculosis, and histoplasmosis were also
      common, sometimes not previously suspected, postmortem findings. This study shows
      that multiple infections occur simultaneously in AIDS patients, and that many
      among them are never suspected before the postmortem examination. These findings
      suggest that an aggressive investigation of infections and cancers should be done
      in patients with AIDS, particularly in those who do not respond to therapy of an
      already recognized condition.

PMID- 9640786
TI  - Amastigotes forms of Trypanosoma cruzi detected in a renal allograft.
AB  - Trypanosoma cruzi, the causative agent of Chagas' disease assumes two distinct
      forms in vertebrate hosts: circulating trypomastigote and tissular amastigote.
      This latter form infects predominantly the myocardium, smooth and skeletal
      muscle, and central nervous system. The present work describes for the first time
      the detection of amastigote forms of T. cruzi in the renal parenchyma of a kidney
      graft recipient one month after transplantation. The patient was serologically
      negative for Chagas' disease and received no blood transfusion prior to
      transplant. The cadaver donor was from an endemic area for Chagas' disease. The
      recipient developed the acute form of the disease with detection of amastigote
      forms of T. cruzi in the renal allograft biopsy and circulating trypomastigote
      forms. The present report demonstrates that T. cruzi can infect the renal
      parenchyma. This mode of transmission warrants in endemic areas of Chagas'
      disease.

PMID- 9640787
TI  - Subcutaneous scedosporiosis. Report of two cases and review of the literature.
AB  - Two cases of subcutaneous scedosporiosis, caused by Scedosporium apiospermum, are
      reported. Both patients had lesions localized in the forearm: a solitary
      ulceration in one and a sporotrichoid-like lesion in the other. The literature is
      reviewed.

PMID- 9640788
TI  - Hantavirus pulmonary syndrome. Report of the first three cases in Sao Paulo,
      Brazil.
AB  - The hantavirus pulmonary syndrome was first recognized in cases that occurred in
      the U.S. in 1993, which served as an alert not only for American physicians but
      also for physicians in other countries for the identification of the disease. In
      the city of Sao Paulo, Brazil, 3 cases of the syndrome were recorded in 1993. The
      patients were young brothers residing in the Mata Atlantica (Atlantic Forest)
      region submitted to recent deforestation. Two of the patients died of acute
      respiratory insufficiency and the third recovered without sequelae. In the
      surviving patient the diagnosis was established by a laboratory criterion based
      on the detection of specific IgM and IgG class antibodies by indirect
      immunofluorescence. In the two patients who died, the diagnosis was confirmed by
      laboratory tests using immunoperoxidase technique for hantavirus in tissue, in
      histological lung and heart sections in one case, and by clinical and
      epidemiological data in the other.

PMID- 9640789
TI  - DOT-enzyme-linked immunosorbent assay (DOT-ELISA) for evaluating IgG antibody
      avidity in toxoplasmosis.

PMID- 9640790
TI  - Hantavirus pulmonary syndrome in the rural area of Juquitiba, Sao Paulo
      metropolitan area, Brazil.

PMID- 9640791
TI  - How can Brazil's post-graduation courses in clinical areas be improved?

PMID- 9640792
TI  - Clinical and radiological postoperative evaluation of posterior sagittal
      anorectoplasty in patients with upper and intermediate anorectal malformations.
AB  - The PSARP is today the most-used surgical technique for correction of high and
      intermediary anorectal malformations. There is much controversy in the literature
      about the post-operative evaluation of these cases. We studied 27 cases of
      anorectal malformations from clinical and radiological aspects, in order to
      analyse: 1. Fecal continence 2. Relationship between post-operative fecal
      continence and the associated sacral anomalies 3. Relationship between the
      radiological evaluation by defecogram and fecal continence From the analysis of
      the cases, we concluded: 1. Fecal continence was achieved in 48.14% of the cases;
      partial continence in 25.92%; and fecal incontinence in 25.92% of the cases. 2.
      The presence of fecal incontinence was directly related to the associated sacral
      anomalies.

PMID- 9640793
TI  - A pioneering experience in Brazil: the creation of a center for assistance and
      research for medical residents (NAPREME) at the Escola Paulista de Medicina,
      Federal University of Sao Paulo.
AB  - The decision to develop a treatment service for medical residents at Escola
      Paulista de Medicina was influenced by three main factors: the suicide of four
      young doctors (2 residents) at this institution between 1995 and 1996, a research
      study that investigated stress among medical residents and the experience of
      other countries in response to similar problems. NAPREME has the following
      objectives: to help to reduce stress among residents, stimulate professional and
      personal development, prevent professional dysfunction and emotional disorders,
      offer psychological treatment, assess the tutors of residency programmes and
      develop research programmes to better identify risk factors for emotional
      problems during the residency period. We hope that by doing this the overall
      quality of the residency programme will improve, both for the professionals and
      the patients.

PMID- 9640794
TI  - Hemorrhagic and thrombotic complications in patients with myeloproliferative
      diseases.
AB  - OBJECTIVE: To correlate the incidence of hemorrhage and thrombosis to bleeding
      time (BT) and platelet aggregation in 27 consecutive patients with
      myeloproliferative diseases (MPD). DESIGN: Retrospective study. SETTING: Public
      tertiary referral center. PATIENTS: Eighteen patients with chronic myelogenous
      leukemia (CML), 5 with polycytemia vera (PV), 2 with essential thrombocytemia
      (ET) and 2 with idiopathic myelofibrosis (MF). Duke's BT and epinephrine-induced
      platelet aggregation were performed on the patients and on 10 healthy
      individuals. RESULTS: Eleven patients presented symptoms (41%):9 with hemorrhage
      (33%) and 5 with thrombosis (19%). There were less symptomatic patients in the
      CML group (28%) than in the other MPD (67%), without statistical significance
      (Fisher, p = 0.06). Duke's BT was longer in symptomatic patients (Mann-Whitney, p
      < 0.05). Platelet aggregation was abnormal in 7 patients (26%) and 71% of them
      were symptomatic (Fisher, p = 0.07). CONCLUSIONS: The high incidence of bleeding
      and thrombosis in patients with MPD was related to prolonged BT, but not to
      platelet aggregation abnormalities.

PMID- 9640795
TI  - Influence of body composition on the bone mass of postmenopausal women.
AB  - AIMS: To investigate the influence of body weight (BW), fat mass (FM) and lean
      mass (LM) on the bone mineral density (BMD) of several areas of the skeleton.
      PARTICIPANTS: Sixty one white postmenopausal women (50.1 +/- 4.8 years).
      MEASUREMENTS: Measurement of BMD by dual energy x-ray absorptiometry. The results
      were analyzed by linear regression and the slopes of each curve were compared.
      RESULTS: The results showed that the correlations between BW, FM and LM to BMD
      were positive, whilst the correlations between age and years since menopause to
      BMD were negative. LM was the main factor that influence BMD in almost all areas.
      CONCLUSIONS: FM and LM present a positive effect on BMD, although LM is the main
      determinant of bone mass. Moreover, higher values of LM and FM present a
      protective effect against the reduction of BMD combined with menopause. Therefore
      postmenopausal women with low BW, especially low LM, present serious risk for
      developing osteoporosis.

PMID- 9640796
TI  - CEA as a prognostic index in colorectal cancer.
AB  - INTRODUCTION: The carcinoembryonic antigen, CEA, is the tumor marker most used in
      colorectal patients, principally during follow up after radical surgery. High
      serum CEA level before surgery is often associated with worse prognosis, in some
      studies. OBJECTIVE: The purpose of this study was to evaluate the preoperative
      carcinoembryonic antigen levels (CEA) and the frequency of recurrence. MATERIAL
      AND METHODS: Eighty-three patients with colorectal cancer at Dukes stages A, B or
      C were evaluated retrospectively. The patients follow up was at least two years
      or to death. CEA was determined in serum by enzyme immunoassay (Sorin Biomedica),
      normal value 0.5ng/ml. RESULTS: Disease recurrence was observed in 32 patients
      (38.5%), 13 Dukes B and 19 Dukes C. Seventy five per cent of the patients with
      CEA higher than 10ng/ml relapsed and 80% of the patients without recurrence had
      normal CEA. Disease recurrence in patients with preoperative elevated CEA
      occurred during the first year of follow up in 56% of the patients. CONCLUSION:
      Although the tumor stage is today the most valuable prognostic variable in
      colorectal cancer, the preoperative CEA value can provide some additional
      information in the prognosis of the patient.

PMID- 9640797
TI  - Uncommon allele in apo AI-CIII-AIV gene cluster in a family with congenital
      generalized lipodystrophy.
AB  - Congenital generalized lipodystrophy is a rare inherited disease. One of its
      features is a disturbance in lipid metabolism characterized by
      hypercholesterolemia and hypertriglyceridemia. A brother and a sister with
      congenital generalized lipodystrophy, an 8-year old male and a 12-year old female
      were studied. The mother and a 6-year old brother were healthy. The genetic
      analysis of Sstl RFLP of the apo AI-CIII-AIV gene cluster showed the presence of
      the rare Sstl allele (S2) in the patients but not in the healthy mother and
      brother. As this uncommon allele has been reported to be related to high plasma
      triglyceride levels, this association could be relevant in explaining in part the
      hypertriglyceridemia observed in these patients.

PMID- 9640798
TI  - Ovarian abscess with spontaneous vaginal drainage.
AB  - The occurrence of a rare ovarian abscess, spontaneously drained through the
      vagina after an abdominal hysterectomy is described. The treatment was an
      oophorectomy. The various forms of primary ovarian abscess are discussed in
      connection with these observations. This case illustrates the need for adequate
      manipulation of the gonad during pelvic surgery in order to avoid parenchymal
      contamination and the subsequent formation of such abscesses.

PMID- 9640799
TI  - Medical controversies and systematic reviews: the heat and the light.

PMID- 9640800
TI  - Microsurgical reconstruction during treatment of oncological diseases of head and
      neck.
AB  - In 37 oncological patients where extensive resections of the face, maxilla,
      mandible or calva were necessary, microsurgical reconstructions were used in 27
      cases as primary operations at the time of resection, and in 10 cases delayed or
      secondary operations were made. 49 flaps were used. In five cases two flaps were
      used in a single stage reconstruction, i.e. one flap for reconstruction of the
      mandible or buccal and on the other for facial side of the face. During
      operations a multidisciplinary approach of the surgical team comprising a
      maxillofacial surgeon, ENT and plastic surgeon is preferred.

PMID- 9640801
TI  - Treatment of a maxillary defect following resection of carcinoma.
AB  - A group of 37 oncological patients with tumours of the head and neck where
      extensive resection of the face, maxilla or mandible or calva was necessary,
      comprised five patients with a typical defect after resection of part of the
      maxilla including half of the palate and exenteration of the orbit. This
      extensive defect causes discomfort to the patient and his environment--functional
      i.e. impaired speech, and cosmetic. A satisfactory solution during reconstruction
      of the maxilla without the need of skeletal reconstruction is microsurgical
      transplantation of a narrow flap of the latissimus dorsi, usually with two
      cutaneous islands--one to close the palate and the other to close the orbit and
      face.

PMID- 9640802
TI  - Functional and aesthetic consequences in the forearm after harvesting the Chinese
      flap.
AB  - We have evaluated the donor site after harvesting the chinese flap in 40 patients
      operated at the Clinic of Plastic and Aesthetic Surgery of Brno between 1989 and
      1994. We conclude that: 1--The hand function is not oustandly altered after
      harvesting the flap, but in our study 11 patients (27.5%) indicated that they
      have some limitation or impairment of their hand function. 2--Tolerance to
      forearm deformity is considerable, but it depends on degree of the defect for
      which the flap is transferred: 25 patients (62.5%) would like to elect a
      different flap. 3--It is necessary to think about cosmetic consequences of the
      chinese flap and consider other possibilities of the flap choice. Secondary
      defect may be for the patient a problem even several years after operation.

PMID- 9640803
TI  - Some thoughts and observations concerning the prevention of neuroma.
AB  - Reliable prevention of neuroma is a problem the solution of which is still
      outstanding. Compared to earlier methods, which mostly consisted in attempts to
      stop axonal proliferation abruptly, it is now coming to be generally accepted
      that the regenerative potential of the axons needs to be reduced gradually. The
      methods most in accord with this view--centro-central anastomosis and capping of
      nerve ends with a nerve or vein graft--are considered, adding personal
      observations. A new variant that has shown special promise in animal experiments
      involves using a nerve and a vein graft in combination. The method still requires
      clinical verification.

PMID- 9640804
TI  - Combined application of alpha-tocopherol and FC-43 perfluorocarbon emulsion
      suppresses early postburn lipid peroxidation and improves deformability of
      erythrocytes.
AB  - The effect of FC-43 perfluorocarbon emulsion and alpha-tocopherol on lipid
      peroxidative damage and deformability of erythrocytes was evaluated in rats (full
      skin thickness burns over 15-20% of total body surface) at third hour after
      burns. The animals were divided into five groups: (1) non-burnt non-treated
      (controls); (2) burnt non-treated; (3) burnt but treated with alpha-tocopherol
      ("Serva", Germany, 20 mg/kg b.m. i.p.) (4) burnt treated with FC-43 emulsion
      ("Green Cross Corp.," Japan, 5 ml/kg, i.v.); (5) burnt treated with combination
      of alpha-tocopherol (20 mg/kg) and FC-43 perfluorocarbon emulsion (5 ml/kg). In
      the burnt non-treated group the concentration of alpha-tocopherol decreased by
      38% (p < 0.05), the levels of malonyl dialdehyde (MDA) and fluorescent damaged
      products raised by 32% (p < 0.001) and by 52% (p < 0.001) of the controls,
      respectively, whereas the deformability of red blood cells diminished by 34% (p <
      0.001). Both the accumulation of MDA and fluorescent lipid peroxidation products
      and the decrease in deformability of affected cells were suppressed significantly
      by alpha-tocopherol treatment which also prevented the decrease in erythrocyte
      alpha-tocopherol content. FC-43 emulsion lowered the level of MDA but did not
      restrain the reduction in erythrocyte deformability significantly. The combined
      application of alpha-tocopherol and FC-43 emulsion immediately after thermal skin
      injury decreases peroxidative membrane damage and improved erythrocyte
      deformability more significantly than alpha-tocopherol at the third hour after
      thermal skin injury.

PMID- 9640805
TI  - The tissue adhesive indermil and its use in surgery.
AB  - Indermil, in relation to the tissue adhesives described remains the state of the
      art with regard to function and clinical outcome. The advantage of an inventory
      sterile tissue adhesive that is to say one that is in the clinic or operating
      theatre ready for immediate use on demand is the requirement of modern surgical
      practice. Cost factors are also an important consideration in today's
      environment. A research study by the Department of Health Economics at the
      University of York found the cost of the Indermil tissue adhesive system
      equivalent to absorbable sutures and produced projected savings per patient in
      relation to conventional sutures with respect to theatre time and return
      patients' visits (6). In parallel a survey of patients showed 90% would prefer
      wound closure by an adhesive in relation to traditional sutures. There are few
      areas of surgical practice which cannot find some application for tissue
      adhesives. The growing international interest in adhesives and their application
      would confirm their importance and potential in surgery.

PMID- 9640806
TI  - Challenges of family planning in Africa.

PMID- 9640807
TI  - Family planning knowledge, attitude and practice amongst males in a Nigerian
      urban population.
AB  - A study to investigate men's knowledge, attitude and practice of family planning
      was carried out in Enugu, South-eastern Nigeria between September and December
      1996. A total of 380 adult working males were studied. A high proportion of the
      respondents had knowledge of and possessed positive attitude to family planning,
      even though a lesser proportion actually used family planning methods. Ninety per
      cent of the respondents accepted the decision that the number of children in the
      family should be made by the couple. While over 32 per cent of the men believed
      that the wife alone should use family planning methods, only 10 per cent thought
      it was the husband's role to use family planning methods. There is need for the
      present integrated national MCH/family planning programmes to be adapted for use
      by men.

PMID- 9640808
TI  - Awareness and use of family planning methods among married women in Ibadan,
      Nigeria.
AB  - A study of awareness and use of family planning methods among 1188 married women
      aged 15-40 years, attending antenatal clinic in four different locations,
      conducted in Ibadan, Nigeria between May to December 1995 is reported. Most
      respondents (94.3%) were aware of the use of family planning but only 12.0% had
      ever visited a family planning clinic. Awareness of specific methods was 82.6%
      for condoms, 75.7% for oral contraceptives, 75.5% for injectable contraceptives
      and 65.3% for intrauterine device. Current use of family planning methods was low
      with 10.0% using withdrawal, 8.1% oral contraceptives, 5.2% using intrauterine
      devices and 4.7% using condoms. Perceived constraints to the use of family
      planning methods included husband's opposition, fear of complications and
      perceived insufficient knowledge about family planning methods. It is concluded
      that there is a knowledge-practice gap in the use of family planning methods
      among married women in Ibadan, Nigeria. Improved education strategies and better
      access to services are needed to solve these problems.

PMID- 9640809
TI  - Pain control in voluntary surgical contraception.
AB  - The reduction of anxiety and control of pain in 1,546 clients undergoing
      voluntary surgical contraception (VSC) is presented. Psychological support
      through adequate counselling and abdominal breathing exercises are vital. General
      anaesthesia was used in 254 (16.4%) of the clients; sedation plus local
      anaesthetic agents in 296 (19.2%) while local anaesthetic alone was used in 996
      (64.4%) of clients. There was progressive shift from the use of general
      anaesthesia (GA) to local anaesthesia (LA), particularly for the minilaparotomy
      procedure following the introduction of Association for Voluntary Surgical
      Contraception (AVSC) programme in our department since this type of anaesthesia
      was cheap, safe, affordable and readily available. Recommendations for successful
      VSC techniques include gentle tissue handling, proper use of the correct
      instruments to reduce painful stimuli, while low dose intravenous sedation should
      be used only when necessary. Minilaparotomy under local anaesthesia (ML/LA) has
      been successfully established in Jos University Teaching Hospital, Jos, Nigeria.

PMID- 9640810
TI  - Evaluation of weaning diets in peri urban Kumasi, Ghana.
AB  - This work evaluates the commonly used weaning diets in peri-urban Kumasi, Ghana,
      in terms of the type of diets, daily energy and nutrient intakes of the infants,
      frequency of feeding, and the chemical composition of the diets. Women with
      children of up to two years old in peri-urban communities of Kumasi municipality
      of Ghana, were interviewed in a cross-sectional survey. One hundred and seventy
      two mothers were randomly sampled and questioned on their socio-economic
      characteristics, types of weaning diets they give to their children, and the
      dietary intakes of their children. Composition of the commonly used weaning
      diets, and the daily energy and protein intakes of the children were determined.
      Liquid weaning diets were introduced at a mean age of 2.2 +/- 2.4 months earlier
      than recommended, but solids were at appropriate time (5-7 months). The energy
      and protein intakes of the children were low, meeting only 49% and 90% of their
      respective recommended daily intakes. This is attributed to the low energy and
      protein densities of the commonly used liquid diet, koko, and low energy and
      nutrient contents of other weaning diets. It is recommended that an innovative
      nutrition education package that re-emphasises the need to introduce weaning
      diets with continued frequent breast feeding to ensure adequate caloric and
      protein intakes should be designed and implemented.

PMID- 9640811
TI  - Upper gastrointestinal mucosal lesions in dyspeptic patients with homozygous
      sickle cell disease in Kenya.
AB  - A case controlled study comprising 51 patients with homozygous sickle cell (HbSS)
      disease who complained of dyspepsia and 41 age and sex matched non-HbSS control
      dyspeptic patients was carried out, to look at upper gastrointestinal mucosal
      lesions associated with dyspepsia. Upper gastrointestinal tract (UGIT) endoscopy
      was performed with gastric control biopsy taken for histology. Thirty two (62.3%)
      of the HbSS or sickle cell anaemia (SCA) patients had upper gastrointestinal
      pathology at endoscopy as compared to 17 (41.5%) of controls. The difference was
      significant at p = 0.042. Bile reflux (47%) was the predominant abnormal
      morphological finding in SCA patients while duodenal ulcer was the most common
      morphological finding in dyspeptic controls. The prevalence of duodenal ulcer in
      controls (22%) though higher than in SCA patients (9.8%), was not statistically
      significant p = 0.18. Gastric ulcer was not found in SCA patients. Duodenal ulcer
      was commoner in males than females in both cases and controls with a ratio of 4:1
      and 3.5:1 respectively. Only four (7.8%) SCA patients and one (2.4%) of controls
      had normal mucosa at histology, the rest had evidence of histological gastritis.
      We could not draw any correlation between non-steroidal anti-inflammatory drugs
      (NSAIDS) use and UGIT findings. Since the proportion of SCA cases with UGIT
      abnormalities was significantly high, we recommend that dyspeptic SCA patients
      undergo UGIT investigations including endoscopy to maximise their clinical care.

PMID- 9640812
TI  - Calcitonin gene-related peptide immunoreactive (CGRP-IR) intradental nerves in
      the dog.
AB  - Calcitonin gene-related peptide (CGRP) is the most frequently occurring peptide
      in sensory neurons in the rat. Most of the Calcitonin Gene-Related Peptide
      Immunoreactive (CGRP-IP) nerves have been found to be Capsaicin-sensitive
      suggesting an involvement in certain types of pain. In the dental pulp CGRP-IR
      nerve fibres have been studied in the rat, guinea pig, cat, sheep, pig, cow and
      horse but not in the dog. Extensive sprouting of CGRP-IP intradental nerves has
      been demonstrated in the teeth with pulpal inflammation in rat molars. In the
      present investigation the occurrence and distribution of CGRP-IR intradental
      nerves both in the normal and the injured and inflamed teeth of the dog was
      studied. Immunolabelling was done by the Avidin-Biotin Complex (ABC)
      immunoperoxidase technique. CGRP-IR intradental nerves were demonstrated in the
      dog. The pattern of distribution was found to be similar to that in other animal
      species. However, the tip one third of the coronal pulp was sparsely innervated
      compared to that in the rat. Also much fewer fibres were seen to penetrate
      predentine and dentine, and this appears characteristic of the dog teeth.
      Sprouting phenomenon seen in the rat was not found in the dog teeth. It is
      suggested that there might be a species difference in the innervation pattern of
      CGRP-IR intradental nerves between the rat molar and the dog canine and incisor
      teeth.

PMID- 9640813
TI  - Relationship between parasite load and immune responses in early stages of
      Leishmania donovani infection in inbred BALB/c mice.
AB  - The aim of this study was to determine if a correlation exists between Leishmania
      donovani parasite load and the corresponding humoral and cellular mediated immune
      responses in the early stages of Leishmania donovani infection in inbred BALB/c
      mice. Five groups of ten BALB/c mice each were inoculated intraperitoneally with
      stationary phase metacyclic promastigotes of Leishmania donovani at doses 1 x
      10(2), 1 x 10(4), 10(6) and 1 x 10(8) respectively per mouse. Group five mice
      were not manipulated in any way and were left to serve as control. At weekly
      intervals, for five weeks, the mice were assayed for cellular mediated immune
      responses to leishmania antigen by the delayed type hypersensitivity skin test
      (DTH) and humoral responses by the direct agglutination test (DAT) and the enzyme
      linked immunosorbent assay (ELISA). A correlation was established between
      parasite load and humoral responses as assayed by DAT and ELISA techniques. This
      study demonstrates that it is possible to diagnose visceral leishmaniasis in
      experimentally infected laboratory mice by DAT and ELISA. These techniques have
      the potential in screening large numbers of animals suspected to be reservoirs of
      visceral leishmaniasis by examining the peripheral blood taken from the tail of
      the animal.

PMID- 9640814
TI  - Antibiotic sensitivity of endemic Shigella in Mbarara, Uganda.
AB  - We analysed the chimio-sensitivity to antibiotics of endemic strains of Shigella
      isolated in Mbarara district, southwest Uganda. Twenty four strains were
      isolated, of which none was sensitive to cotrimoxazole and eight (33.4%, 95% CI
      [15.6-55.3]) to ampicillin, the two antibiotics recommended to treat dysentery
      during non epidemic periods in Uganda. Two isolates were resistant to nalidixic
      acid and none was resistant to the fluoroquinolones (Ciprofloxacin, Norfloxacin).
      It is concluded that the results of this survey could be used to facilitate the
      elaboration of a new treatment protocol to treat endemic dysentery cases in
      Uganda.

PMID- 9640815
TI  - In-vitro activity of piperacillin and tazobactam combination against clinically
      significant bacteria.
AB  - The in-vitro activity of piperacillin/tazobactum which is not among the routinely
      tested antibiotic at the Public Health Bacteriology Laboratory, Parirenyatwa
      Hospital, Harare, Zimbabwe was evaluated for its activity against bacterial
      pathogens using the Kirby-Bauer disk diffusion method. Piperacillin/tazobactum
      showed superior in-vitro activity against both gram positive and gram negative
      bacteria when compared with routinely tested antibiotics such as gentamicin,
      erythromycin, tetracycline, penicillin, chloramphenicol, fusidic acid and
      clindamycin and the difference was statistically significant (p < 0.05).
      Ciprofloxacin showed in-vitro activity comparable to that of
      tazobactam/piperacillin. Specifically, 96% of gram positive isolates (comprising
      Streptococcus pyogenes, Staphylococcus aureus, coagulase negative staphylococci
      and Streptococcus pneumoniae were sensitive to piperacillin/tazobactam. For gram
      negative organisms, 98% of Haemophilus influenzae Shigella spp, Klebsiella spp
      were also sensitive to the combination. The broad spectrum of activity of
      piperacillin/tazobactam shows that the potential of the drug combination for the
      treatment of infections caused by diverse microorganisms should not be
      underestimated. We recommend its inclusion in routine antibiotic sensitivity
      testing in our hospital.

PMID- 9640816
TI  - Health effects of cassava consumption in south Ethiopia.
AB  - Health problems associated with cassava consumption was studied in three villages
      (Kodowono, Lotte and Woidewashe) of Gamo-Gofa, South Ethiopia. Total goitre rate
      (% TGR) increased with increasing rate of cassava consumption while, urinary
      iodine excretion (UIE) was found to be in the normal value range for the three
      villages. In both males and females incidence of goitre after the introduction of
      cassava to Kodowono village was significantly higher than before introduction of
      cassava (p < 0.001). This may indicate that the high rate of goitre is attributed
      to the frequency of cassava consumption. Of 450 individuals interviewed for
      health problems associated with cassava meal consumption, 50% reported that they
      were suffering from epigastric burning pain and dizziness while 38.7% reported
      abdominal distention and vomiting. Vomiting was relatively higher in the age
      group 20 years and below than it was in those above 20 years of age. These
      problems may be attributed to cassava consumption because, cassava contains
      cyanide which results in intoxication when poorly processed cassava meal is
      taken. Goitre prevalence and health problems attributed to cassava consumption
      therefore, necessitate an intervention programme to control iodine deficiency
      disorders (IDD), develop appropriate processing techniques to eliminate cassava
      toxicity and educate villagers on how to prepare safer meals from cassava.

PMID- 9640817
TI  - Smoking--an emerging risk factor for renal diseases.
AB  - The health, economic and social costs of smoking are enormous and well known to
      physicians. Smoking results in a lot of morbidity and mortality mainly related to
      cardiovascular disease, cancer and pulmonary disease. The effect of smoking on
      the kidneys is little appreciated. It is the purpose of this review article to
      give evidence from available literature that smoking is indeed deleterious to the
      kidneys and may result in progression of chronic renal failure to end stage renal
      disease. It is concluded that nephrologists, and indeed all physicians, should
      make a concerted effort to save their patients from this vice.

PMID- 9640818
TI  - Human antibody response to Moraxella catarrhalis antigens.
AB  - Moraxella catarrhalis was isolated from 68 of 200 (34%) sputum and 56 (28%)
      nasopharyngeal swab samples of patients with community-acquired pneumonia. Of the
      68 pneumonia patients, 42 (61.8%) were males and 26 (38.2%) females. Fifty one of
      the 68 patients (75%) had chronic underlying diseases. beta-lactamase was
      produced by 37 (54.4%) of the 68 sputum samples and 32(57.1%) of the 56
      nasopharyngeal isolates. In an ELISA using outer membrane protein antigens of M.
      catarrhalis against patient sera showed 40 of 68 (58.8%), and 43 of 68 (63.2%)
      significant increase in convalescent to acute sera when IgA, IgM and IgG3 were
      used respectively. In control sera only of 30(3.3%) and none showed significant
      antibody rise when IgA, IgM and IgG3 conjugates were used respectively (P <
      0.05).

PMID- 9640819
TI  - Surgery in a rural hospital: experience from northern Nigeria.
AB  - Over a 5-year period in a rural hospital in Northern Nigeria, 949 patients were
      operated on, constituting 84.7% of all surgical admissions. Nearly one half were
      emergency procedures. The majority of the patients were young (mean age 36.0
      years) and predominantly male (M:F = 1.5:1). A wide variety of surgical
      procedures were performed but overall 85% were not of a complex nature. Mortality
      was 4.8%, due mostly to septic complications. It is suggested that most of the
      surgical procedures in rural Africa can be performed by general duty doctors with
      surgical experience and they should be taught and encouraged to perform these
      operations. The importance of relevant research to solve local problems is
      highlighted and the planning of primary health care to include more primary
      surgery emphasised.

PMID- 9640820
TI  - Cholelithiasis in young Saudi women.
AB  - We studied some of the factors associated with gallstones in a sub population of
      Saudi women who presented with cholelithiasis at a rather young age, 17-30 years.
      We determined the weight, height, ideal weight, overweight, Quetelet index, ideal
      Quetelet index, and parity in 152 such women designated the study group and in
      another aged matched group of 152 women without biliary disease designated the
      control group. Although the mean weights of both groups were greater than ideal,
      the mean weight, level of overweight, and mean Quetelet index in the study group
      were greater than those of the controls at virtually all age groups (p > 0.001).
      In the study group, comparison of the 17-25 year olds with the 26-30 year olds
      showed close similarity in weight, Q index, and level of overweight (p = 0.50).
      There was no significant difference in parity between the study group and the
      controls. We conclude that obesity is a significant factor in the development of
      cholelithiasis in Saudi women who develop symptomatic gallstones in the age group
      17-30 years.

PMID- 9640821
TI  - Recurrent varicose veins.
AB  - Recurrence of varicose veins after treatment has been reported as being between
      7% and 65%. During the five month period from August to December 1993, 400
      operations on 265 patients were performed for varicose vein disease. Of these, 53
      patients had presented with recurrent vein disease in 72 limbs (18%). All
      patients underwent Duplex scanning of their deep and superficial systems and
      sites of venous incompetence were identified. The sapheno-femoral junction (SFJ)
      was found to be incompetent in 52 limbs, of which 31 had previously undergone
      flush ligation. Sapheno-popliteal junction (SPJ) was incompetent in 33 limbs,
      while the long saphenous vein (LSV) was found to be incompetent in 67 cases.
      There were no major complications in this group. Minor complications occurred in
      10 cases (14%), mainly in the form of thigh paraesthesia. The more common causes
      of recurrent disease have been identified and therefore, it should be possible to
      reduce its incidence. Duplex scanning is essential for any unit dealing with
      recurrence.

PMID- 9640822
TI  - Relapse of Hodgkin's disease after 10 years of complete remission: case report.
AB  - A 17 year old male patient with nodular sclerosis Hodgkin's disease had a relapse
      of lymphocyte depleted type ten years after entering complete remission with
      chemotherapy and radiotherapy. This is the first documented case in our
      experience of relapse after very long disease free interval. A review of the
      literature of late relapses in Hodgkin's disease is also presented. Relapses have
      been recorded from three years to twenty years, although few very late forms are
      registered. Long term follow up will be necessary to document the role of the
      different therapeutic regimen.

PMID- 9640823
TI  - Recent infectious disease outbreaks in Kenya: have we been caught unaware?

PMID- 9640824
TI  - Pattern of resolution of tachypnoea and fever in childhood pneumonia.
AB  - Acute lower respiratory infections (ALRI) account for one fifth of deaths among
      children below five years of age and pneumonia is responsible for about 70% of
      all ALRI deaths. Interventions with antibiotics have shown reduction in pneumonia
      case-fatality rates. However, there is room for further reduction of deaths from
      pneumonia through improved monitoring and follow up system. We studied the
      pattern of resolution of tachypnoea and fever among 108 children who presented to
      our outpatient clinic with non-severe pneumonia and among 102 children who were
      admitted for severe pneumonia. We found that tachypnoea was present in 18% and
      23% after 72 hours of initiation of antibiotics and fever resolved completely
      after 48 hours and 72 hours of initiation of therapy in non-severe cases of
      pneumonia among children two to 11 months and 12 to 59 months of age
      respectively. Conversely, among cases of severe pneumonia on day 5 of initiation
      of treatment, tachypnoea and fever were present in 65% and 51% respectively in
      children two to 11 months old and in 53% and 60% respectively in children 12 to
      59 months old. Respiratory rate increased with increase in body temperature at an
      average rate of four breaths per minute for every 1 degree C rise. Our study
      suggests that body temperature and respiratory rate can be used to monitor the
      clinical course of non-severe pneumonia. Further research is needed to identify
      other clinical signs that will help the health worker to decide improvement in
      attacks of severe pneumonia.

PMID- 9640825
TI  - Selected laboratory tests in febrile patients in Kampala, Uganda.
AB  - A study was undertaken to determine the role of typhoid in febrile illness. It
      was found that in 1992, Salmonella typhi, the causative agent of typhoid, played
      a 2.3% role in 25404 diagnostic specimens sent to Mulago Hospital, Kampala, the
      largest hospital in Uganda. The rates of isolation fell gradually from 2.3% in
      1992 to 0.3% by 1995. Instead malaria was found to play a major role in febrile
      illnesses. Out of 355 patients attending a private clinic in Kampala, whose blood
      was examined for both malaria and typhoid, 97% were positive for malaria
      parasites compared to 0.84% with significant O and H Salmonella typhi antibody
      titres of > 1:80. Also malaria parasites were found in 60% (out of 105) of
      patients who had had persistent fevers and in whom doctors had also requested for
      HIV antibodies. Those who had HIV antibodies alone were six per cent and the ones
      with both were 28%, a finding which showed relatively low association of malaria
      and HIV. Where multiple tests were requested on one patient having general
      malaise or body joint pains and/or constant headaches, malaria was found to play
      a major role (73%) compared to syphilis (4.3%) and brucellosis (13.3%). Malaria
      parasites were seen in normal sizes and in somehow young or stunted forms. The
      latter were found more often in patients who had experienced one or a combination
      of the following: intermittent fevers, backache, headache, tiredness, joint
      and/or neck pains, and who had already received treatment for malaria.

PMID- 9640826
TI  - Bacterial meningitis in children admitted in hospitals within Nairobi.
AB  - Four hundred and ninety nine children (aged between one month and five years)
      admitted with clinical features of meningitis were recruited in cross-sectional
      survey of bacterial meningitis in hospitals within Nairobi. Lumbar punctures were
      done on all of them and the cerebrospinal fluid (CSF) analysed bacteriologically
      and serologically for the common causative organisms. Two hundred and fifty
      (50.1%) cases were diagnosed clinically as having meningitis. Of these, 132
      (52.8%) had turbid CSF specimens, while 118 (47.2%) were clear. When turbid CSF
      specimens were cultured, 83 (62.8%) yielded three common bacterial micro
      organisms namely; Neisseria meningitidis, Streptococcus pneumoniae and
      Haemophilus influenzae in that order of frequency. The implications of these
      findings in paediatric meningitis together with the drug sensitivity patterns is
      presented and discussed.

PMID- 9640827
TI  - Cytoprotective effects of alpha tocopherol against liver injury induced by
      extrahepatic biliary obstruction.
AB  - There are several important aetiologies of extrahepatic biliary obstruction
      (EBO). If EBO is surgically reconstructed in the critical time period, liver
      damage can be halted or reversed. In this golden period, lipid peroxidations
      significantly intensify liver defects. We hypothesised that alpha tocopherol
      (alpha-T) could protect the liver from the damage caused by response to EBO. In
      standard conditions, albino rats of Wistar strain were divided into two groups.
      All rats underwent double ligations and divisions of common bile ducts (CBD). One
      of these groups received alpha-T (CBDL-alpha-T). The other CBDL animals received
      intramuscular injections of normal saline (CBDL-NS). Serum samples were taken for
      biochemical analyses by light microscopy. The data showed a decrease in plasma
      bilirubin and liver enzyme levels in CBDL-alpha-T group, when compared with CBDL
      NS (p < 0.05). Morphologic analyses showed better results for CBD-alpha-T. Serum
      levels of Malonyldialdehyd (MDA) in the CBDL-alpha-T group was 9.2 +/- 3.4 nmol/g
      compared to that in CBDL-NS, 12.3 +/- 4.4 nmol/g (p < 0.05). In conclusion, a
      dramatic protective effect of alpha-T on functional and structural features of
      the liver in rats with EBO was demonstrated. The data suggest that EBO may cause
      liver damage by stimulation of lipid peroxidation and that alpha-T may slow down
      liver damage in this setting.

PMID- 9640828
TI  - Appendicitis among African patients at King Edward VIII Hospital, Durban, South
      Africa: a review.
AB  - This retrospective study of 645 black patients, carried out over a five year
      period, showed that appendicitis is twice as common in males as in females and
      that it occurs predominantly in young people (median age 20 years). The classical
      presentation of periumbilical pain (16%) was outnumbered by right iliac fossa
      pain (36%) and non-specific pain (27%). The majority perforated (43%) and
      appendiceal inflammation was second commonest (37%). The negative appendicectomy
      rate was 8.8% and there was a diagnostic error of 14%. Mortality was two per cent
      mainly from patients complicated by peritonitis. Hospital stay was 7 +/- 7 days,
      with the longest stay following peritonitis. A diagnosis of appendicitis should
      always be entertained in an African patient presenting with an acute abdomen and,
      where the diagnosis is in doubt, a laparotomy should be performed.

PMID- 9640829
TI  - Endoscopic findings and prevalence of Helicobacter pylori in Kenyan patients with
      dyspepsia.
AB  - One hundred and twenty consecutive patients above 12 years of age with dyspepsia
      were studied from June 1993 to September 1994. They underwent upper
      gastrointestinal endoscopy to find the mucosal lesions which were associated with
      their dyspeptic symptoms. At endoscopy gastric mucosal biopsies were taken in
      order to identify Helicobacter pylori (H. pylori) using three different
      techniques: culture, histology and the rapid urease test. Normal looking mucosa
      was the commonest single endoscopic finding, accounting for 34.2%, followed by
      gastritis 31.7% and duodenal ulcer 29.2%. However, when duodenal ulcers and
      gastric ulcers were put together, then peptic ulcer was the most prevalent
      finding accounting for 38.4%. Peptic ulcer was the most prevalent pathological
      finding in both young (less than 50 years) and older patients (50 years and
      above). Duodenal ulcer was more prevalent than gastric ulcer in the younger age
      group with a ratio of 5.8:1, however, the ratio in the older age group was 1:1.
      Gastric cancer was only found in patients aged 50 years and above, accounting for
      17.4% of dyspeptic symptoms in this age group. Females were found to have more
      normal endoscopic findings than males (59.6%, versus 17.8% respectively). The
      difference being statistically significant (p < 0.001). All our cases of peptic
      ulcer disease had evidence of H. pylori infection while dyspeptic patients with
      normal endoscopic mucosal findings had H. pylori in 80.5% of cases. The
      difference in prevalence of H. pylori in the two groups was statistically
      significant (p < 0.001). Surprisingly, evidence of H. pylori in gastric cancer
      cases was very low in this study, being found in only 25% of patients.

PMID- 9640830
TI  - Pattern of peptic ulcer disease in Zaria, Nigeria.
AB  - The pattern of peptic ulcer disease in Zaria has been that of an increasing
      frequency of perforation, reaching a peak of 45% by 1983. In a retrospective
      study of 88 consecutive patients managed surgically for duodenal and gastric
      ulcers between 1984 and 1995, 41% had gastric outlet obstruction and only 17% had
      perforation. However, the ratio of perforated duodenal ulcer: perforated gastric
      ulcer has more than doubled from 2.6:1 to 6.5:1. Until now the pattern of peptic
      ulcer disease in northern Nigeria was different from that in southern Nigeria and
      most parts of black Africa but this review suggests a reversion to the pattern in
      these other places. Though these findings may be due to the effects of a changing
      economy, they may represent a change in the intrinsic behaviour of peptic ulcers
      in our environment. Ulcer perforation continues to carry a high mortality and
      truncal vagotomy and drainage remains the surgical treatment of choice for
      duodenal and gastric ulcers in our institution.

PMID- 9640831
TI  - Caretakers' perceptions of clinical manifestations of childhood malaria in holo
      endemic rural communities in Tanzania.
AB  - A cross-sectional household survey was carried out in Kibaha district, Tanzania
      to obtain caretakers' knowledge on symptoms of childhood malaria in children
      under five years of age in relation to its management. A total of 1530 caretakers
      were interviewed, 620 (40.5%) reporting malaria attacks among their children in
      the last three months of which, 432 (70%) reported that the attacks were severe.
      Only 15.7% (68/432) of those reporting severe attacks could mention convulsions
      as symptoms of severe malaria, while fever and vomiting were mentioned as
      symptoms of severe malaria by 93.3% (403/432) and 52.3% (226/432) of the care
      takers respectively. Higher level of education was significantly associated with
      knowledge of symptoms of severe malaria, also with promptness in taking
      management action. The fact that most of the caretakers reported fever and
      vomiting as symptoms of severe malaria, and hence the observed high proportion of
      reported severe malaria, implies that the communities under study do not perceive
      febrile convulsion as being a symptom of severe malaria. The implication of these
      findings on the control of malaria through treatment on demand are discussed.

PMID- 9640832
TI  - Wild polio virus surveillance in the sewage system of selected communities at the
      risk of poliomyelitis in southwest Nigeria.
AB  - Twenty two sewage samples collected from eleven locations among communities at
      risk of poliomyelitis in the southwestern part of Nigeria were screened for the
      presence of polio virus. The virus was isolated from seven of the samples. All
      the isolates were type 1 wild polio virus, an indication that all the isolates
      were from human contamination and that the wild polio virus is still very much in
      circulation in Nigeria many years after the Expanded Programme on Immunisation
      was introduced. It can be concluded from this study that polio immunisation
      campaign has not been successful in Nigeria considering the number of wild polio
      virus isolated from the sewage samples since virological examination of sewage
      has been used to document the effect of vaccination campaigns.

PMID- 9640833
TI  - Cryptosporidium and other parasites in Ethiopian AIDS patients with chronic
      diarrhoea.
AB  - Previous studies in other African countries have shown high prevalences of
      Isospora belli and Cryptosporidium parvum infections in acquired immunodeficiency
      syndrome (AIDS) patients with chronic diarrhoea. However, there is lack of
      information regarding these infectious agents in Ethiopian AIDS patients. Thus,
      this investigation has been aimed at determining the prevalence of
      Cryptosporidium and other related gastrointestinal parasites in AIDS patients
      with diarrhoea in seven Addis Ababa hospitals. Stool specimens from 246
      clinically diagnosed AIDS patients were parasitologically screened for parasitic
      infections constituting HIV-negative with diarrhoea and HIV-positive without
      diarrhoea control groups. A variety of intestinal protozoa and helminths were
      found in 50% of AIDS patients and 42% of the controls. Cryptosporidiosis was
      detected in 38(25.9%), Isosporiasis in two (1.4%), and Blastocystosis in one
      (0.7%) of the AIDS patients with diarrhoea. The occurrence of cryptosporidiosis
      among the AIDS patients and possible explanation of the increasingly high study
      subjects with diarrhoea but without identifiable parasites is discussed.

PMID- 9640834
TI  - Obstetric outcome in the unbooked mother.
AB  - This study aimed at determining the outcome of pregnancy in unbooked mothers with
      regard to maternal complications and foetal outcome. This retrospective study was
      based on investigations of medical records of 467 unbooked mothers who presented
      for delivery at the Obstetrics Unit at King Khalid University Hospital, Riyadh,
      during the period 1991 and 1992, and 415 booked mothers with regular clinic
      attendance selected as controls. Data collected from the records included
      patients' socio-demographic characteristics, past obstetric history, prevalence
      of pregnancy-related diseases, and data relating to labour, delivery, and foetal
      outcome. Chi-square test and Fisher's exact test were used for assessing the
      statistical significance of the association between the various factors which
      were investigated. The tendency for mothers to be booked was found to be
      significantly associated with their age, occupation, parity, and gestational age
      at delivery. Booked and unbooked mothers did not differ significantly in relation
      to the mode of delivery and foetal outcome, although the prevalence of previous
      complications of pregnancy was generally lower among unbooked mothers. There was
      no statistically significant association between the absence of antenatal care
      and outcome of pregnancies, unbooked mothers had a higher proportion of MICU
      admissions and dead babies compared with the controls. Educating the community
      about the benefits of receiving regular antenatal care, even if at primary care
      level, may be of great importance in improving the pregnancy outcome.

PMID- 9640836
TI  - Injury pattern during team handball competition in east Africa.
AB  - Team handball is a fast, explosive sport, and injury risk is inevitable. There is
      need to define the risk factors in order to formulate preventive, treatment and
      rehabilitation measures. This study investigated the nature, aetiology, mechanism
      and anatomical localisation of injuries observed among male and female players
      during the tenth edition of the East and Central Africa Senior Clubs
      Championships (9th-17th April, 1995) in Nairobi, Kenya. There were nine male and
      five female teams from Kenya, Uganda, Tanzania and Ethiopia which played nineteen
      and ten matches respectively leading to 52(77.61%) and 15(22.39%) injuries. The
      matches were observed and the injuries recorded live by trained researchers and
      the result confirmed after the match. The commonest injuries were contusions
      (64.18%). Most injuries were caused by another person (85.07%), majority of them
      occurring due to collision (55.22%). The head suffered most injuries (59.24%) and
      many players got more injured while attacking than defending. In all, 56.7% of
      the injuries were observed in the second half. Generally, only 38.81% of the
      injuries led to a substitution of player. This pattern of injuries was the same
      for both male and female players. More studies of this nature are recommended in
      order to clearly define injury risk in team handball and, thus, preventive,
      treatment and rehabilitation measures.

PMID- 9640835
TI  - Rehabilitation of heroin and cocaine abusers managed in a Nigerian psychiatric
      hospital.
AB  - Eighty patients, managed primarily for heroin and cocaine dependence at the Drug
      Rehabilitation Unit of Psychiatric Hospital, Yaba, Lagos, were followed up
      monthly for a period of 12 months post-discharge and assessed with regard to
      continued substance use, employment status and illegal activities. The management
      package included full assessment, detoxification, treatment of associated
      physical conditions, group therapy sessions, occupational and vocational
      rehabilitation. The sample was predominantly male (91%), young adults (mean age
      29.1 years; SD 5.99) and single (58%). Although 95% had some formal education,
      many were school drop-outs, and only 31.3% were gainfully employed. The majority
      (84%), used a combination of heroin and cocaine, almost all on a daily basis,
      mainly by smoking and "chasing the dragon" (95%). Other substances reportedly
      used preadmission were alcohol (22.5%), cannabis (76.3%) and tobacco (97.5%).
      Less than one half (43.8%) completed the minimum one month required for inpatient
      treatment. Only seven (8.7%) attended the follow-up clinic regularly, but all
      defaulters were assessed in their homes. The level of heroin, cocaine and
      cannabis use, as well as report of illegal activities, dropped sharply from the
      first month post-discharge, but started to rise again (albeit slowly) by the
      second half of the follow-up period. There was only a slight insignificant gain
      in employment status of patients during the follow-up period. The community-based
      management approach is strongly advocated as a way of addressing the several
      factors identified in this study as militating against the successful management
      of substance abusers.

PMID- 9640837
TI  - Chloroquine and cardiac arrhythmia: case report.
AB  - A case of a sixty two year old white man with Plasmodium vivax malaria, who has
      shown chloroquine associated acute cardiac arrhythmia is reported.

PMID- 9640838
TI  - Opsoclonus-myoclonus associated with traditional medicine ingestion: case report.
AB  - A case of Opsoclonus-Myoclonus occurring in a young man, in association with
      traditional herbal medicine consumption is presented. Clinical and laboratory
      investigations did not reveal any of the known aetiological associations of the
      Opsoclonus-Myoclonus syndrome, raising the possibility that the traditional
      herbal medicine may be aetiologically implicated. This report highlights the need
      for proper identification and documentation of the contents of common herbal
      remedies and their possible side effects amongst Africans.

PMID- 9640839
TI  - Cervicofacial actinomycosis after partial mandibular resection: case report.
AB  - An unusual case of cervicofacial actinomycosis in a 60-year old male Nigerian is
      reported. The patient had had partial mandibular resection for plexiform
      ameloblastoma one year earlier with insertion of Kirschner wire to serve as a
      splint. The authors highlight the possible pathophysiology of this condition. It
      is suggested that clinicians be aware of the various modes of presentation and
      natural history of the disease to facilitate prompt diagnosis and appropriate
      treatment. This will assist in forestalling the numerous complications that may
      result from actinomycosis.

PMID- 9640840
TI  - Gastro-intestinal tuberculosis: an emerging diagnostic dilemma.
AB  - Nine cases of gastrointestinal tract tuberculosis seen by the author in 1995/96
      are reported. In all the patients, the final diagnosis could only be established
      histologically. Pre-operative clinical examination and investigations had
      suggested otherwise. Six of these patients were HIV positive. This communication
      suggests that immunocompromised individuals are at increased risk of
      gastrointestinal tuberculosis. Clinicians, therefore, should bear in mind
      possible co-existence of gastrointestinal tract (GIT) tuberculosis and HIV when
      dealing with patients suffering from gastrointestinal tract diseases of unknown
      origin.

PMID- 9640841
TI  - Unusual neuropsychiatric manifestations of hypoparathyroidism: report of two
      cases.
AB  - Clinical, laboratory and radiological features of two cases of hypoparathyroidism
      presenting with pure neurological disease are described. The first patient has
      choreoathetosis and the second has mutism, locked jaw bilateral papilloedema and
      generalised tonic clonic epilepsy. Computerised tomography of the brain showed
      extensive calcification in the gray and white matter in both cases. Such
      combination of neurological manifestation of the disease and extensive cerebral
      calcification is rarely encountered and reported. It is concluded that brain
      calcification, which is generally believed to be asymptomatic, can cause frank
      neurological disease when it is extensive.

PMID- 9640842
TI  - Cancer cell cycle and adoptive immunotherapy using lymphokine-activated killer
      cells.
AB  - The mechanism underlying the lymphokine-activated killer (LAK) cell cytotoxicity
      to tumor cells in LAK therapy was studied using flow cytometric cell cycle
      analysis of Daudi cells. It was suggested that the degree of LAK cell
      cytotoxicity varied depending upon the phase of the cell cycle that the Daudi
      cells were in: the resting (G0)-phase/preparation for DNA synthesis (G1)-phase,
      the DNA synthesis (S)-phase or the preparation for mitosis (G2)-phase/mitosis (M)
      phase. The levels of expression of intercellular adhesion molecule-1 (ICAM-1),
      lymphocyte function-associated antigen-3 (LFA-3) and fibronectin (FN), surface
      antigens playing important roles in LAK cell cytotoxicity, in the different
      phases of the Daudi cell cycle have been investigated. The level of the
      expression of ICAM-1 and LFA-3 was significantly higher in S-phase cells and G2/M
      phase cells relative to that in G0/G1 phase cells. The level of expression of FN,
      however, was significantly lower in S-phase cells and G2/M-phase cells in
      relation to that in G0/G1 phase cells. On the basis of these results, it may be
      inferred that the degree of LAK cell cytotoxicity is closely related to the cell
      cycle phase that the Daudi cells are in and the level of expression of surface
      antigens associated with the cell cycle phase. For Daudi cells treated with cis
      diamminedichloroplatinum (II) (CDDP) and mitomycin-c (MMC), the enhancement of
      the degree of LAK cell cytotoxicity was directly related to the decrease in the
      proportion of cells in the S-phase. It may be suggested, therefore, that the
      proportion of cells in the S-phase in a tumor serves as an index of the
      sensitivity of the tumor cells to LAK cell cytotoxicity, and that designing a
      therapeutic strategy on the basis of the analysis of tumor cell cycle would help
      to improve the success of LAK therapy.

PMID- 9640843
TI  - Enhancement of eosinophil survival by lipopolysaccharide through releasing
      granulocyte-macrophage colony stimulating factor from mononuclear cells from
      patients with bronchial asthma.
AB  - BACKGROUND: The mechanism of bronchoobstruction in asthmatics following
      inhalation of lipopolysaccharide (LPS) is unclear. OBJECTIVE: In this study we
      have investigated the effects of the LPS on eosinophil survival rate in
      stimulating peripheral blood mononuclear cells (PBMCs) from patients with asthma.
      METHODS: PBMC supernatants from 10 asthmatic patients and 4 healthy subjects were
      compared for eosinophil survival rate using the same purified eosinophils. Two x
      10(6) cells/ml of PBMCs were cultured for 24 hours in RPMI 1640 containing 10%
      fetal bovine serum along with 10 micrograms/ml of LPS. 10(6) cells/ml of
      eosinophils were incubated for 96 hours in the presence of PBMC-derived culture
      supernatants at 75% in volume. RESULTS: The viability of eosinophils incubated
      with PBMC supernatants from asthmatic patients stimulated with LPS was higher,
      62.5% +/- 10.6% (mean +/- SD), than that without LPS, 26.9% +/- 10.8%, and also
      higher than that of PBMCs from healthy subjects with LPS, 40.0% +/- 15.4%. This
      increasing activity of asthmatic PBMC stimulated with LPS was markedly inhibited
      from 72.2% +/- 9.7% to 38.5% +/- 6.8% by addition of mouse anti-human GM-CSF
      antibody to the PBMC supernatant but not mouse anti-human IL-5 antibody.
      CONCLUSION: These results suggest that LPS enhances eosinophil survival in
      asthmatics by increasing the production of GM-CSF from PBMCs.

PMID- 9640844
TI  - Intranuclear expression of cyclin D1 protein as a useful prognostic marker for
      mantle cell lymphoma.
AB  - Mantle cell lymphoma (MCL) has a characteristic chromosomal translocation,
      t(11:14) (q13;q32) involving rearrangement of bcl-1 locus, and the key oncogene
      of bcl-1 locus in PRAD1/cyclin D1 gene that encodes the protein regarding cell
      cycle. Recently, several studies using immunohistochemical and molecular methods
      have demonstrated the overexpression of cyclin D1 mRNA/protein in cases of MCL.
      We have studied immunohistochemical expression of cyclin D1 protein on frozen
      sections of 27 cases of MCLs and evaluated the relationship between the
      expression of cyclin D1 and prognosis. Sixteen (59.3%) cases showed intranuclear
      staining of cyclin D1 protein and 6 of 7 cases examined using RT-PCR methods
      showed the overexpression of PRAD1/cyclin D1 mRNA. The data indicate that
      intranuclear staining of cyclin D1 protein is associated with the overexpression
      of PRAD1/cyclin D1 mRNA. The survival time of cyclin-D1 positive group was
      shorter than that of cyclin D1-negative group, and there was a significant
      difference in survival time between the two groups (p < 0.05; log-rank test).
      These data suggest that the MCLs with overexpression of PRAD1/cyclin D1 protein
      has poor prognosis, and intranuclear expression of cyclin D1 protein is a useful
      prognostic marker for MCL.

PMID- 9640845
TI  - Substances reactive with mannose-binding protein (MBP) in sera of patients with
      rheumatoid arthritis.
AB  - OBJECTIVES: In order to evaluate the role of mannose-binding protein (MBP) in
      rheumatoid arthritis, we characterized MBP-binding substances in sera of patients
      with this disease. METHODS: An enzyme linked immunosorbent assay (ELISA) was used
      to detect MBP-binding substances in sera of patients with RA. We applied the sera
      of two RA patients to an immobilized MBP column, and by means of both ELISA and
      molecular sieve chromatography, examined the substances that bound to MBP. MBP
      MASP complexes were added to the fractions containing the binding substances, and
      C4-consuming activity was examined. RESULTS: Sera of patients with RA showed
      stronger MBP binding on ELISA than did those of normal controls. In the case of
      RA sera, both IgG was IgM-RF eluted from the MBP column, whereas with normal
      controls, only IgG was obtained. The results of molecular sieve chromatography
      showed that the binding substances of RA patients consisted of immune complexes
      containing IgG and IgM-RF. These substances were specifically bound to MBP, and
      once bound, the MBP-MASP complexes were then able to consume C4. CONCLUSION: MBP
      binds to immune complexes consisting of IgG and IgM-RF, and probably recognizes
      either the mannose moiety of IgM-RF or the N-acetyl-glucosamine of agalactosyl
      IgG. When this occurs in RA patients, the lectin pathway would then be activated.

PMID- 9640846
TI  - A case of retroperitoneal abscess: an unusual complication of cholecystitis and
      choledocholithiasis.
AB  - A man, 73 years old, who developed acute biliary tract infection complicated with
      retroperitoneal abscess formation in iliopsoas region was reported. The magnetic
      resonance imaging was especially effective to delineate the lesion, extending
      from the subhepatic down to the iliopsoas muscle. The echo-guided fine needle
      aspiration technique was successful to make the lesion subside.

PMID- 9640847
TI  - Frequency of grandparent contact with grandchild sets: six factors that make a
      difference.
AB  - Using data from the second wave of the National Survey of Families and
      Households, the authors examine the determinants of frequent and infrequent
      visiting between grandparents and their grandchild sets. A grandchild set
      consists of all the children of a particular child of the grandparent, provided
      that the grandchildren reside in their parent's household. The 6 significant
      predictors of frequent or infrequent contact are geographic distance, quality of
      relationship between grandparent and parent of the grandchild set, number of
      grandchild sets, gender of grandparent, lineage of the grandchild set, and
      marital status of the grandparent.

PMID- 9640848
TI  - Constant hierarchic patterns of physical functioning across seven populations in
      five countries.
AB  - This research was aimed at identifying critical steps in the decline in physical
      function that often parallels aging. Six basic and nine instrumental activities
      of daily living (ADLs) were classified into four domains of disability
      characterized by specific underlying physical impairment. The hierarchical order
      of this classification was verified in two random samples representative of the
      older home-dwelling population. The concordance level of disability and results
      of performance-based measures of physical function were also tested. Finally, the
      cross-cultural reliability of the model was verified in seven population-based
      samples of older persons living in five European countries. In older persons the
      disabling process follows a general pattern of progression based on a typical
      sequence of impairments.

PMID- 9640849
TI  - Recruiting research participants: a comparison of the costs and effectiveness of
      five recruitment strategies.
AB  - Among the major costs associated with conducting survey research are the time and
      money spent recruiting a large and racially representative sample. Contrasted
      here are the costs of different recruitment strategies (agencies, support groups,
      snowballs, media, mass mailings) in terms of project time, supplies (e.g.,
      postage, support materials), and staff time as they bear on the costs of
      recruiting 841 older mothers of offspring with lifelong disabilities. Results
      indicate that the costs of recruitment vary by method and race. Whereas agencies,
      support groups, and snowball recruitment were low- to moderate-cost strategies,
      they were less effective for recruiting African Americans than were media and
      demographic sampling unit strategies. These analyses suggest that with
      appropriate planning, funding, and implementation, nonprobability sampling
      methods can be used successfully to recruit a large and diverse sample.
      Suggestions for improving the implementation of future recruitment campaigns are
      also offered.

PMID- 9640850
TI  - Satisfaction with outpatient geriatric evaluation and management (GEM).
AB  - The purpose of this study was to evaluate high-risk older adults' satisfaction
      with outpatient geriatric evaluation and management (GEM). Community-dwelling
      Medicare beneficiaries (n = 522) age 70 years and older who had a high
      probability of repeated admission to hospitals (Pra > .40) were randomly assigned
      to receive either usual care or GEM for six months. Despite the stresses imposed
      by outpatient GEM (e.g., new relationships with providers, frequent office visits
      and changes in treatments), the mean satisfaction scores of the recipients of GEM
      were 9% higher than those of the recipients of usual care (4.31 vs 3.96, p <
      .001). The primary physicians of GEM recipients were also highly satisfied with
      GEM care.

PMID- 9640851
TI  - Awareness and utilization of community long-term care services by elderly Korean
      and non-Hispanic white Americans.
AB  - This article presents a comparative analysis of the level of awareness and
      utilization of 15 community-based long-term care services by 213 elderly Korean
      and 201 non-Hispanic White Americans. We found extremely low levels of awareness
      and utilization of long-term health and social services among Korean Americans,
      in both absolute and relative terms. This finding challenges the success of the
      Older Americans Act, an important funding source of those services, in meeting
      its stated objectives to increase service availability and delivery to minority
      elders and socioeconomically disadvantaged elders. Strategies for effective
      outreach and public education efforts are also discussed.

PMID- 9640852
TI  - Profiles of hospital, physician, and home health service use by older persons in
      rural areas.
AB  - Using data from the Medicare Current Beneficiary Survey, we identify differences
      in hospital days, home health visits and physician office visits across five
      geographical categories. After controlling for individual characteristics and
      availability of health care providers, we find significant differences in service
      use. Results show greater use of home health care and less use of physician
      office visits and hospital care in rural areas. Because service use exhibits
      patterns of substitution and complementarity, future research on the use of
      health services needs to move beyond modeling the use of single services to
      modeling the range of services used.

PMID- 9640853
TI  - The impact of female caregivers' employment status on patterns of formal and
      informal eldercare.
AB  - This article uses data from the 1989 National Long-Term Care Survey and its
      companion Informal Caregivers Survey to investigate how the employment of female
      primary caregivers (FPCGs) affects hours of care received by disabled elderly
      care recipients (CRs). Multivariage analyses controlling for key FPCG and CR
      characteristics indicate that when FPCGs are employed they provide significantly
      fewer hours of care personally; however, their CRs also receive significantly
      more hours of help from other sources. When FPCGs work more than 17 hours per
      week, their CRs receive significantly fewer total weekly hours of care than would
      otherwise be the case.

PMID- 9640854
TI  - Listening to caregiving sons: misunderstood realities.
AB  - In-depth interviews with 30 sons actively involved in caring for a parent with
      dementia expand the understanding of sons' caregiving experiences. The within
      group analysis revealed common themes that emerged from the narratives--duty,
      acceptance, taking charge, common emotions, and work flexibility--as well as
      common issues--loss, sibling relationships, role reversal, coping strategies, and
      positive outcomes. The interviews also generated a typology of son caregivers
      that included such types as the dutiful son, the son who goes the extra mile, the
      strategic planner, and the son who shares the care.

PMID- 9640855
TI  - Interracial and intraracial differences in neuropsychiatric symptoms,
      sociodemography, and treatment among nursing home patients with dementia.
AB  - Using an adaptation of George's (1989) social antecedent model of
      psychopathology, this article examines interracial and intraracial differences in
      neuropsychiatric symptoms, sociodemography, and treatment among nursing home
      patients with dementia. The final sample consisted of 164 U.S.-born African
      Americans, 54 African Caribbeans, and 68 Caucasians. Although there were
      appreciable interracial differences in sociodemographics, there were minimal
      clinical differences. This finding may reflect both racial differences in
      pathways to institutionalization and the homogenization of clinical
      characteristics created by new governmental standards for nursing homes. There
      were no substantial differences between African Americans and African Caribbeans.
      Use of medication to treat neuropsychiatric symptoms was low, and may have
      reflected difficulties in diagnosis and concerns about the abuse of medications.

PMID- 9640856
TI  - Retention of administrators in nursing homes: what can management do?
AB  - Annual turnover among nursing home administrators may be 40% or higher. To
      investigate the factors that could lead to greater administrator retention,
      responses to a survey (53% response rate) were analyzed using factor analysis and
      multiple regression models. Results show that higher retention is observed when
      administrators are allowed to function independently, are involved in decision
      making, are treated fairly, and are given reasonable goals to achieve.
      Organizations must hire administrators whose values match theirs. Multifacility
      chain organizations and for-profit facilities appear to have a greater need to
      embrace organizational principles that lead to greater job satisfaction.

PMID- 9640857
TI  - In their own words: nursing assistants' perceptions of barriers to implementation
      of prompted voiding in long-term care.
AB  - Prompted voiding is an effective intervention for the improvement of continence
      in long-term care. This study investigated certified nursing assistants' (CNAs)
      perceptions of incontinence etiologies, as well as perceived barriers to prompted
      voiding implementation. A questionnaire was administered to CNAs in 23 long-term
      care facilities. Data analysis was conducted using descriptive statistics and
      correspondence analysis. CNAs perceived prompted voiding as helpful; however,
      inadequate staffing, workload, and turnover/absenteeism hindered implementation.
      CNA recommendations for long-term success included increased staff, staff
      support, improved communication, ongoing education, and alternative delivery
      models of care.

PMID- 9640858
TI  - Teaching and maintaining behavior management skills with nursing assistants in a
      nursing home.
AB  - This article describes a nursing staff training program in basic behavior
      management skills and a formal staff management system to encourage the
      application of these basic skills on the nursing unit. Behavioral skills training
      consists of a 5-hour in-service followed by three weeks of on-the-job training to
      ensure accurate application of behavior management skills. Following training, a
      staff management system is used to facilitate long-term use of the skills.
      Components of the staff management system include supervisory monitoring of the
      nursing assistants (NAs) by licensed practical nurses (LPNs), NA self-monitoring,
      verbal and written performance feedback, and incentives.

PMID- 9640859
TI  - [Antepartum amniotic fluid index and pregnancy outcome].
AB  - Our purpose was to evaluate prognostic value of antepartum amniotic fluid index
      (AFI) on fetal and newborn outcome, because oligohydramnion is associated with
      increased risk of fetal and newborn distress. Perinatal outcome was defined by 1'
      and 5' Apgar score, intrapartum fetal heart rate (FHR), blood gas, acid-base
      status in umbilical artery, mode of delivery and meconium-stained amniotic fluid.
      Data was analysed with CSS Statistica for Windows package by test t for
      independent samples and chi 2. Prospective observations was conducted with 84
      singleton pregnancies complicated by oligohydramnion (AFI < or = 5 cm). A 336
      pregnant women, with normal amniotic fluid index and no complicated pregnancy,
      was considered as controls. No increased operative delivery and meconium-stained
      amniotic fluid rate was noted. There was no significant effects AFI on blood
      gases in umbilical artery and Apgar score. Oligohydramnion was associated with
      increased risk of fetal acidosis (pH < 7.16) (p = 0.009) and abnormalities of FHR
      (variable decelerations) (p = 0.004). Reduced AFI had poor predictive value of
      fetal acidosis and newborn depression positive predictive value (8-13%).
      Summarizing the results, our investigation showed that amniotic fluid index is
      only one point in the prognosis of perinatal outcome.

PMID- 9640860
TI  - [Salt taste perception in women during physiological pregnancy].
AB  - The authors studied a sensory intensity response to sodium chloride (NaCl) and a
      sensory hedonic response to salt in suprathreshold concentrations in 120 healthy
      primigravidas (age: 20-40) during three trimesters of physiological pregnancy,
      and in 22 healthy nonpregnant women of the same age examined on the 7th or 8th
      day of the menstrual cycle. In all the periods covered by the study, pregnant
      women have manifested a tendency to a lower intensity response to all
      concentrations in comparison with nonpregnant women. The weakening of the
      response has become statistically significant in the second trimester--with
      respect to low concentrations, and at the final stage of pregnancy--with respect
      to medium concentrations. The sensory hedonic response in pregnant women has been
      increasing along with the age of the fetus. In comparison with the response of
      nonpregnant women, pregnant women have shown a tendency to the intensified
      response in all the periods covered by the study.

PMID- 9640861
TI  - [Diagnosis of human parvovirus B19 infection in nonimmune hydrops fetalis].
AB  - Parvovirus B19 (PV B19) infection was investigated in 29 pregnant women with
      fetal hydrops, after exclusion of feto-maternal incompatibility within red blood
      cell antigens, TORCH infections, feto-maternal hemorrhage and genetics reasons.
      The active viral infection was detected in 9 women (31%) by PCR amplification of
      DNA B19; in 2 of them IgM and IgG, in 1 IgM and in 4 IgG antibodies were also
      present. In 6 women (20%) IgG antibodies were only found, but not IgM and DNA
      B19, which confirmed infection in the past. In addition in 9 cases DNA B19 was
      evaluated in the fetal blood. The results in the mothers and their fetuses were
      concordant (4 positive, 5 negative). Our conclusion is that in nonimmune hydrops
      fetalis, PV B19 infection should be based on the viral DNA evaluation in the
      blood of mother (or fetus). IgM antibodies, in time of fetal disorders, might not
      be detected.

PMID- 9640862
TI  - [Flow cytometric analysis of cord blood lymphocytes].
AB  - It has been observed that immunological reactivity of neonatal leukocytes is
      diminished. It seems to result from lymphocytes immaturity. In the present study
      we have evaluated the phenotype of cord blood lymphocytes with the use of flow
      cytometry. In neonates we have observed the increase in the absolute number of
      CD1a and CD7 positive lymphocytes as well as CD2, CD3, CD4, CD8, CD16, CD19 and
      CD20 positive, while number of CD57 positive cells was significantly decreased.
      The ratios of CD4/CD8 and T/B lymphocytes were similar to the corresponding
      ratios observed in adults. Our results have shown the presence of immature
      lymphocyte population as well quantitative depletion of subpopulation of CD57
      cells, what may pose an increased risk of infection in neonates. Nevertheless,
      increased number of T and B lymphocytes with mature phenotype along with normal
      ratio of lymphocyte subpopulations and increased number of CD16 positive cells
      (NK cells), may explain phenomenon of good health among majority of newborns.

PMID- 9640863
TI  - [Adenoid cystic carcinoma of the breast. Analysis of 7 patients].
AB  - A retrospective analysis of 7 patients with adenoid cystic carcinoma of the
      breast operated at Center of Oncology in Krakow is presented. Ten years without
      evidence of disease survived 6 (85.7%) patients. One patient only, with poorly
      differentiated carcinoma, presented axillary metastases and died of metastases to
      the lungs and hepar.

PMID- 9640864
TI  - [Dependence of serous activity of cathepsin B on histological types of ovarian
      carcinomas].
AB  - The preoperative activity of cathepsin B was determined in the serum of 110
      patients with primary ovarian carcinomas and in 35 women with benign ovarian
      tumor. The significant increase of cathepsin B activity in ovarian carcinomas is
      independent of its types in comparison to benign ovarian tumor. The percentage of
      the results with value above the cut-off values was the highest for serous types
      of ovarian carcinomas. The dependence between the increase of cathepsin B
      activity and the FIGO stage of the disease was observed only for serous and
      endometrioid type of ovarian carcinomas.

PMID- 9640865
TI  - [Results of surgical treatment of vulvar cancer].
AB  - OBJECTIVES: Vulvar cancer is a relatively rare genital malignancy. The mainstay
      of it's treatment is surgery. DESIGN: A retrospective study of vulvar cancer
      patients treated between 1967 and 1995 at Department of Gynaecology, Medical
      University of Gdansk. MATERIALS AND METHODS: The type and outcome of surgical
      treatment was studied in 162 consecutive patients. RESULTS: The surgery was
      limited to the vulva in 24% cases and in the reaming 76% of patients removed were
      also regional lymph nodes. Median survived of the whole group was 105 months and
      actuarial 5-year survival-60%. CONCLUSIONS: The results of treatment of vulvar
      cancer in presented series correspond well with the literature data.

PMID- 9640866
TI  - [Familial complex chromosome translocation of t(1;4;10)(q21.3;q27;q26.1) verified
      by FISH].
AB  - The inheritance complex chromosome translocation is a rare. A familial complex
      chromosome rearrangement t(1;4;10)(q21.3;q27;q26.1) involving three chromosomes
      ascertained due to four spontaneous abortions in phenotypically normal childless
      woman there is presented. Cytogenetic analysis according to classic banding
      techniques were verified by fluorescent in situ hybridization (FISH) technique.

PMID- 9640867
TI  - [The repeated ignoring of prenatal care by a pregnant woman after kidney
      transplantation].
AB  - A multipara after kidney transplantation who had for the second time completely
      neglected prenatal care was admitted to a delivery room at the end of the first
      stage of labour. She delivered a daughter, weight 2900 g, Apgar 9 points.
      Mother's puerperium was without complications. The transient oliguria occurred in
      the baby on the second day. The problems connected with pregnancy after kidney
      transplantation were discussed.

PMID- 9640868
TI  - [The case of intrauterine pregnancy coexisting with extrauterine pregnancy which
      was surgically removed].
AB  - The case of simultaneous intrauterine and ruptured ectopic pregnancy was
      presented. The diagnosis of coexisting intrauterine and ectopic pregnancies is
      difficult. The patient was admitted to the clinic because of abdominal pain and
      vaginal bleeding in the 10th week of pregnancy has been treated by laparotomy.
      The intrauterine pregnancy was continued successfully to term. The importance of
      careful sonographic examination of adnexal region was stressed in all symptomatic
      patients with first trimester pregnancy.

PMID- 9640869
TI  - [Intrauterine growth retardation (IUGR) vs small for gestational age fetus (SGA).
      Diagnostic aspects].
AB  - Fetal growth deficiency and low birthweight requires an accurate assessment and
      may be divided into two groups: 1. Intrauterine growth retardation (IUGR) which
      is strongly associated with a fetal structural malformation, infections (TORCH)
      and utreoplacental dysfunction considered to be the most common cause. 2.
      Genetically, constitutionally small baby (SGA) classified as a well-nourished,
      healthy and short baby. Taking into account clinical data, medical history,
      health state of a patient, serial ultrasound growth scan, Doppler ultrasound,
      cardiotocography and enzymatic monitoring may proved to be useful to
      differentiate between these two problems.

PMID- 9640870
TI  - Calcium hydroxyapatite deposition disease of the neck: finding in three patients.
AB  - Calcium hydroxyapatite deposition disease may occasionally involve the
      superolateral portion of the longus colli muscle. Clinical symptoms include
      headache, neck pain, and dysphagia. Characteristic prevertebral calcifications
      with the epicenter at the C1-C2 level are depicted on lateral radiographs of the
      cervical spine.

PMID- 9640871
TI  - [Computed tomographic diagnosis of biliary ileus].
AB  - Rare in the general population, gallstone ileus accounts for 25 per cent of
      nonstrangulated small bowel obstructions in patients over the age of 65. While
      mortality has declined over the years, it remains high at 12-17 per cent. This is
      largely due to the insidious symptoms making the diagnosis difficult and to the
      aged patient population, with frequent comorbid medical conditions contributing
      to mortality. Much better than plain radiograph and probably easier than
      ultrasound, CT makes the correct diagnosis of the classical triad of Rigler:
      distended small bowel loops, pneumobilia and an ectopic calcified gallstone. We
      report two cases promptly and specifically diagnosed with CT. The second case was
      a very rare Bouveret's Syndrome, a gastric outlet obstruction caused by a
      gallstone. Patients were treated by a one time associated enterolithotomy and
      cholecystectomy. We recommend the early use of abdominal CT scanning for the
      investigation of clinical bowel obstruction in the elderly, where gallstone ileus
      is a more common condition.

PMID- 9640872
TI  - Giant fibrovascular polyp of the esophagus.
AB  - We report on a patient who presented a fibrovascular polyp of the esophagus,
      which is an uncommon submucosal tumor that can attain giant proportions. It is
      covered with squamous epithelium and consists of a mixture of myxoid-collagenous
      fibrous elements, vascular structures and adipose cells. Diagnosis is made via
      upper endoscopy, echoendosonography and barium studies. CT and MR imaging can be
      helpful for full evaluation of this rare lesion.

PMID- 9640873
TI  - Glenoid dysplasia: radiographic and CT arthrographic findings.
AB  - A 60-year-old man with dysplasia of the glenoid and a rotator cuff tear is
      reported on. Because of the tear, CT arthrography was performed, offering an
      opportunity to evaluate the various soft tissue abnormalities accompanying
      glenoid dysplasia. Marked thickening of the glenoid cartilage and labrum was
      apparent, as well as an abnormal posterolateral orientation of the glenoid
      cavity. A deep notch was observed along the central portion of the glenoid
      cartilage. Furthermore the middle glenohumeral ligament appeared thickened and
      cordlike.

PMID- 9640874
TI  - Chronic recurrent multifocal osteomyelitis.
AB  - The case of a 17-year-old boy with Chronic Recurrent Multifocal Osteomyelitis
      (CRMO) is presented. Clinical manifestations included a three month history of
      marked antalgic scoliosis, thoracic and mid-sternal pain, mild fever, elevated
      erythrocyte sedimentation rate, and skin lesions such as acne and psoriasis.
      Radiologically, osteolytic lesions were seen in the sternum and the thoracic
      spine. Histopathological examination of the sternal lesion revealed chronic
      osteomyelitis. Bone cultures of the resected specimen were negative for known
      pathogens. The combination of the clinical, radiological, histopathological and
      microbiological features was the clue to the diagnosis of CRMO.

PMID- 9640875
TI  - Temporal lobe abscess as a complication of cholesteatoma: sequential radiological
      findings.
AB  - Temporal lobe abscess is a rare but known complication of petrosal bone
      cholesteatoma. We present a case with clinical history, diagnostic imaging and
      sequential radiological findings of the abscess from the early temporal
      cerebritis phase till the late full encapsulated abscess. We also succeeded in
      visualizing the fistula through the tegmen tympani on MR-images.

PMID- 9640876
TI  - CT findings in splenic tuberculosis.
AB  - Splenic tuberculosis is rare and delay in diagnosis is common. We present two
      cases of splenic tuberculosis with their appearance on CT. The CT findings were
      multiple, round or ovoid, low-density lesions without calcification. Except for
      non-specific lymphadenopathy no abnormality nor history suggestive of
      tuberculosis was revealed prior to laparotomy. Although CT does not confirm a
      diagnosis of splenic tuberculosis, it would be a valuable examination to define
      the extent of disease and guide aspiration biopsy.

PMID- 9640877
TI  - [Screening for breast cancer: the time of decision].
AB  - The purpose of this review article is to propose the basic rules of a
      scientifically correct breast cancer mass screening. It might give to the
      different authorities arguments to make a choice between an organized screening
      and some trials currently used in our country.

PMID- 9640878
TI  - Chronic critical limb ischemia: what is the benefit of radiological intervention?
      Indications and results.
AB  - Indications of interventional radiological procedures in patients with chronic
      critical limb ischemia are not clearly defined. PTA of limb arteries is used only
      in 3 of 4% of patients, although 20 to 40% might be candidates for a proximal
      intervention in the iliac arteries. Following PTA of intrapopliteal arteries,
      limb salvage varies from 56 to 82% and arterial patency rate from 34 to 100%
      after 1 to 2 years follow-up in non controlled case series studies. Arterial
      local thrombolysis shows better results than surgery in subgroups of patients in
      a few studies. Pulse spray technique does not show better clinical results than
      conventional infusion of the plasminogen activator. Overall, radiological
      interventions give similar results compared with surgery, concerning limb salvage
      rate, length of hospital stay, morbidity and mortality, but significantly more
      patients are discharged home versus a nursing institution after radiological
      treatment than after surgery. Radiological techniques seem to be cost effective
      compared to surgery. Amputation should be carried out only after all
      revascularization possibilities have been ruled out at a multidisciplinary
      vascular center.

PMID- 9640879
TI  - [Gastric diverticulum simulating a left adrenal mass].

PMID- 9640880
TI  - Permeability barrier abnormality of hairless mouse epidermis after topical
      corticosteroid: characterization of stratum corneum lipids by ruthenium tetroxide
      staining and high-performance thin-layer chromatography.
AB  - Topical corticosteroids (TCS) are among the most frequently used topical
      therapeutics. Recently, it has been shown that TCS not only has antiproliferative
      actions, but also inhibits the differentiation of the epidermis and finally
      perturbates stratum corneum (s.c.) barrier function. It is well established that
      epidermal barrier function resides within the intercellular lipids of the SC.
      However, to date, little is known about the effects of TCS on the structure and
      composition of s.c. lipids. We therefore used hairless mouse skin to study the
      sequential changes of the s.c. permeability barrier and their intercellular
      lipids by ruthenium tetroxide staining and high-performance thin-layer
      chromatography (HPTLC) during topical use of corticosteroids. The results
      demonstrated a progressive increase in transepidermal water loss accompanied by a
      diminution in the SC intercellular lipid lamellae, which showed a normal
      structure of individual lamella. Analysis of lipid composition by HPTLC after a 6
      week application of TCS also showed an obvious decrease in all the main
      components of s.c. lipids, which are known to constitute the permeability barrier
      of the skin. In light of these results, our work provides direct morphological
      evidence that TCS deteriorates the permeability barrier of epidermis when applied
      to normal skin.

PMID- 9640881
TI  - A preliminary study aimed at the detection of Leishmania parasites in subjects
      with cutaneous leishmaniasis using polymerase chain reaction.
AB  - As a basic study for future diagnosis of cutaneous leishmaniasis, we tried to
      detect Leishmania parasites representing different species in the subgenera
      Leishmania and Viannia from subject patients with cutaneous leishmaniasis by
      using the polymerase chain reaction (PCR) with the subgenus Viannia specific
      primer. Four out of the 14 specimens revealed an amplified DNA of 70 bp specific
      for the subgenus Viannia (L. braziliensis complex). No bands were detected in the
      rest of the specimens belonging to the subgenus Leishmania and unclassified
      groups. The base sequences of the amplified DNA corresponded with those of the L.
      (V). braziliensis kinetoplast minicircle. We concluded that PCR using the present
      primer specific for the subgenus Viannia would be useful in detecting Leishmania
      parasites in lesions of cutaneous leishmaniasis caused by the L. braziliensis
      complex.

PMID- 9640882
TI  - Topical PUVA therapy for chronic hand eczema.
AB  - Seventeen patients with persistent chronic hand eczema were treated with topical
      0.1% 8-methoxypsoralen and UVA (PUVA) for 8 weeks. Significant improvement was
      achieved in 5 cases (29%), moderate improvement in 9 (53%), and little
      improvement in 3 (18%). The mean number of PUVA treatments was 22.2, and the mean
      total UVA dose was 63.5 J/cm2. There was no association between clinical response
      and duration of hand eczema, positive patch test reaction, or atopic status.
      Since topical PUVA has no risk of systemic side effects, it should be considered
      as an alternative treatment for patients with chronic hand eczema who are
      resistant to other topical medications.

PMID- 9640883
TI  - Membranous and soluble forms of Fas antigen in cutaneous lupus erythematosus.
AB  - The role of Fas-mediated apoptosis in cutaneous lupus erythematosus (LE) is still
      unclear, although the Fas/FasL system has been investigated in autoimmune
      diseases in relation to impaired apoptosis. In order to elucidate the connections
      between acute cutaneous LE (ACLE) and chronic cutaneous LE (CCLE), we determined
      the expression of membranous Fas antigen (mFas) on peripheral blood mononuclear
      cells (PBMC) by flow cytometry and the levels of the soluble form of the Fas
      antigen (sFas) in sera. The ratio and the mean fluorescence intensity of mFas
      were much higher in ACLE patients than in others, including patients with CCLE
      and atopic dermatitis and normal healthy controls. The levels of sFas in ACLE and
      CCLE patients were also elevated, and there was a significant increase in sFas
      levels in ACLE patients over that in CCLE patients. Immunohistochemical studies
      revealed that Fas antigen was predominantly expressed on infiltrating cells
      around blood vessels and appendages in ACLE and CCLE patients. Based on these
      findings, it is suggested that the expression of Fas antigen is closely
      associated with the activation of circulating lymphocytes, especially in ACLE
      patients, but is not directly associated with keratinocyte damage.

PMID- 9640884
TI  - Treatment of molluscum contagiosum in males with an analog of imiquimod 1% in
      cream: a placebo-controlled, double-blind study.
AB  - The objective of this double-blind, placebo-controlled study was to evaluate in
      males the clinical efficacy in treating molluscum contagiosum and tolerance of an
      analog of imiquimod (1%) in cream. One hundred patients between 9 and 27 years of
      age (mean 16.3), with 733 lesions (mean 7.3), whose size ranged from 2 to 5 mm
      diameter (mean spot size 3.4 mm) and a biopsy-confirmed diagnosis of molluscum
      contagiosum were randomized into two parallel groups. In a double-blind manner,
      precoded 40-g tubes were dispensed. Patients self-administered the trial
      medication to their lesions at home three times daily for five consecutive days
      per week. The study was scheduled with 4 weeks of active treatment (maximum 60
      topical applications) and 12 months (on a monthly basis) of follow-up. Patients
      were examined on a weekly basis. Thirteen patients had atopic dermatitis. A
      clinically and histopathologically confirmed total elimination of lesions was
      considered as cured. After four weeks of treatment, 49 patients and 372 lesions
      were cured. Breaking the code revealed that imiquimod cream had cured 82% of the
      patients and 86.3% of the lesions. Placebo cleared 16% of the patients and 63 of
      the lesions (p < 0.0001). During the treatment, 88% of the patients experienced
      no allergic, localized, or drug-related adverse symptoms. Twelve patients,
      predominantly in the imiquimod cream group reported non-objective, drug-induced,
      mild reactions with no dropouts. The study was followed-up for 12 months. Among
      49 cured patients, 3 had relapses after 10 months. In conclusion, the study
      demonstrated that 1% imiquimod analog in cream with mild subjective side effects
      is significantly more efficacious than the placebo in curing molluscum
      contagiosum in males.

PMID- 9640885
TI  - Sarcomatoid carcinoma of the skin: report of a case.
AB  - We report the histological, immunohistochemical and ultrastructural findings of
      an exophytic cutaneous tumor composed of a mixture of typical basal cell
      carcinoma (BCC) and malignant fibrous histiocytoma. Nine previously reported
      carcinosarcomas of the skin are reviewed. We prefer the term "sarcomatoid
      carcinoma" for this rare neoplasm. Only the BCC showed a positive immunoreaction
      to cytokeratin; the sarcomatous component was negative, but it did express
      vimentin, and, focally, smooth-muscle-specific actin and KP1 (CD68). Both
      components showed p53 immunostaining.

PMID- 9640886
TI  - Diagnostic pitfalls of Merkel cell carcinoma and dramatic response to
      chemotherapy.
AB  - Merkel cell carcinoma (MCC) is an unusual malignant tumor that arises from
      neuroendocrine cells with features of epithelial differentiation. We describe a
      MCC patient with unusual clinical, histopathological, and immunohistochemical
      features. Although the microscopic, immunohistochemical, and ultrastructural
      characteristics of MCC have been well defined, diagnostic difficulties remain,
      particularly in distinguishing it from lymphoma involving the skin, as suggested
      by our case. This is an unusual case in which dense lymphoid infiltration masked
      the true tumor. All the immunohistochemical markers of MCC except neuron-specific
      enolase (NSE) were negative. The dramatic response to primary chemotherapy was
      also very noteworthy.

PMID- 9640887
TI  - A case of rudimentary meningocele.
AB  - A 2-year-old girl had an alopecic, atrophied macule on the midline of the
      occipital area. X-ray and CT scan of the scalp revealed no underlying bone
      defect. Histologically, the whole dermis and subcutis showed dense, hyalinized
      collagen bundles intermingled with cuboidal, epithelioid cells that surrounded
      pseudovascular spaces or gathered in clusters. These flattened or cuboidal cells
      were positive for anti-vimentin antibody; some of them were also positive for an
      anti-epithelial membrane antigen antibody, but negative for antifactor VIII
      related antigen and Ulex europaeus I lectin.

PMID- 9640888
TI  - Intralymphatic embolic cells with cutaneous endometriosis in the umbilicus.
AB  - Endometriosis is defined as the presence of both functioning endometrial glands
      and stroma outside their usual location lining the uterine cavity. It has been
      identified in virtually all tissues and organs of the female body with the
      exception of the spleen. There have been many theories proposed regarding the
      etiology and pathogenesis of endometriosis. One is the transport of cells through
      lymphatics and blood vessels. A 44-year-old female suffering from an episode of
      endometriosis of the umbilicus, left inguinal, uterus, and bilateral ovaries in
      association with a Mullerian anomaly is presented. Histopathological findings of
      a skin biopsy from her umbilicus showed aggregated cells within the lymphatic
      vessel of the upper dermis. This case provides evidence suggesting that cutaneous
      endometriosis could occur by transport of endometrial cells through lymphatics or
      blood vessels.

PMID- 9640889
TI  - Superficial spreading melanoma arising in a longstanding melanocytic nevus on the
      sole.
AB  - In Asians, the plantar surface is the commonest site for cutaneous melanoma, and
      most melanomas arising in this region are the acral lentiginous type. Herein we
      describe a rare case of superficial spreading melanoma arising in a longstanding
      melanocytic nevus on the sole of a Korean.

PMID- 9640890
TI  - Leopard syndrome: a tropical rarity.
AB  - This is a case report of a classical presentation of the Leopard syndrome from
      the Indian subcontinent. The male patient had progressively increasing
      generalised multiple lentiginosis, ocular hypertelorism, pulmonary stenosis,
      short stature, cryptorchidism, and pectus excavatum. The case is documented for
      its rarity in this part of the world and typical clinical presentation.

PMID- 9640891
TI  - Gigantic pyoderma gangrenosum.
AB  - A 71-year-old Japanese female with gigantic pyoderma gangrenosum is reported. The
      pyoderma lesions had been treated as an infectious condition for seventeen months
      and had extended to enormously large areas. The nature of the chronic type of
      pyoderma gangrenosum may need to be stressed, even for dermatologists.

PMID- 9640892
TI  - Recurrent herpes zoster.

PMID- 9640893
TI  - Association of psoriasis vulgaris with Sjogren's syndrome.

PMID- 9640894
TI  - Effects of televised safety models on children's risk taking and hazard
      identification.
AB  - OBJECTIVE: To examine effects of televised safety models on children's
      willingness to take physical risks and their ability to identify injury hazards
      in common situations. METHODS: Sixty children, between the ages of five and eight
      years, were exposed to one of three TV stimulus programs: (1) a safety
      educational videotape, in which actors engaged in dangerous behavior, suffered
      injuries, and then enacted alternative safe behaviors; (2) an animated cartoon,
      which portrayed characters engaged in safety behaviors incidental to the main
      story line; or (3) the same cartoon program edited to omit the scenes depicting
      safety behavior. Children's willingness to take physical risks was measured
      before and after the TV stimulus by a series of pictorial child-relevant
      scenarios in which they could indicate the level of risk they would take. They
      also completed pretest and posttest measures of hazard identification, in which
      they were to identify injury hazards in several pictorial scenarios. RESULTS:
      Exposure to the safety educational videotape decreased children's willingness to
      take physical risks and increased their identification of injury hazards.
      Exposure to the animated cartoon with incidental safety components did not affect
      risk taking, but did increase ability to identify hazards. CONCLUSIONS: Findings
      are interpreted as evidence of observational learning and priming of thematically
      related knowledge by the television stimuli. Implications for safety educational
      curricula are discussed.

PMID- 9640895
TI  - Commentary: television, children's health and safety behavior, and pediatric
      psychology.

PMID- 9640896
TI  - Social functioning of children surviving bone marrow transplantation.
AB  - OBJECTIVE: To evaluate the behavioral reputation and peer acceptance of pediatric
      bone marrow transplant (BMT) survivors. METHODS: Forty-eight BMT survivors (8-16
      years of age) were compared to 48 nonchronically ill, same-classroom, same-gender
      comparison peers (COMP). Peer, teacher, and self-report data were collected.
      RESULTS: Relative to COMP, BMT survivors had fewer friends and were described by
      peers, but not teacher or self-report, as more socially isolated. In addition,
      peers described BMT survivors as being less physically attractive and
      athletically skilled. Further analyses suggested that these nonsocial attributes
      (physical appearance and athletic ability) and treatment variables (whether
      cranial irradiation was received) mediated the social difficulties of BMT
      survivors. CONCLUSIONS: These data are suggestive of an unremitting pattern of
      difficulties with peers that has the potential to disrupt normal social and
      emotional development. Differences between peer, teacher and self-reports
      highlight the need for multiple informants in future work.

PMID- 9640897
TI  - Behavior problems in children with diabetes: disentangling possible scoring
      confounds on the Child Behavior Checklist.
AB  - OBJECTIVE: The Child Behavior Checklist (CBCL; T. M. Achenbach, 1991), when used
      to assess the behavior of children with diabetes, may contain confounds because
      some behavioral items can have a physiologic etiology, and may skew reports of
      behavioral disturbance. METHODS: Two techniques were used to disentangle possible
      scoring confounds in the behavioral ratings of children with and without
      diabetes: (1) the Somatic Complaints scale was deleted, or (2) Diabetes Items,
      identified a priori with 89% agreement by nine medical personnel, were deleted.
      RESULTS: As expected, with traditionally scored protocols, children with diabetes
      obtained higher Internalizing and Total Behavior Problem scores than controls.
      This group difference persisted whether the Somatic Complaints scale or the
      Diabetes Items were deleted. CONCLUSIONS: Compared to controls, children with
      diabetes obtained mildly elevated scores on six of the eight CBCL scales,
      regardless of scoring method, suggesting that their mildly elevated behavioral
      profile is not confounded by physiologic symptomatology.

PMID- 9640899
TI  - Effects of maternal intelligence, marital status, income, and home environment on
      cognitive development of low birthweight infants.
AB  - OBJECTIVE: To examine direct and mediated effects of maternal IQ, marital status,
      family income, and quality of the home environment on the cognitive development
      of low birthweight infants. METHODS: Secondary analyses on a large dataset using
      hierarchical regression identified factors correlated with cognitive outcomes in
      children at 3 years of age who were born at low birthweight. RESULTS: Maternal IQ
      was a critical variable, because it was highly correlated with child IQ and
      because maternal intelligence influenced patterns of relationships among other
      predictor variables including marital status, income level, and home environment
      on child IQ. Analyses revealed that effects of these variables on child IQ
      interacted with maternal IQ. CONCLUSIONS: Early childhood intervention programs
      should target those low birthweight infants most at risk for impaired cognitive
      development. Children at greatest risk are those living with unmarried, low IQ
      mothers.

PMID- 9640898
TI  - Concepts of illness in Icelandic children.
AB  - OBJECTIVE: To investigate the development of illness concepts among healthy
      Icelandic children. METHODS: Participants were 68 schoolchildren, 6-7, 10-11, and
      14-15 years of age, and their parents. Cognitive developmental level and
      understanding of physical illness were assessed within a Piagetian framework. In
      addition, illness experience and illness behaviors (Child Illness Behavior
      Questionnaire) were assessed. RESULTS: Results were consistent with previous
      studies in that the development of illness concepts among Icelandic children was
      consistent with Piaget's theory of cognitive development. No relation was found
      between illness experience and understanding of illness. A more mature
      understanding of illness was related to willingness to report the onset of
      illness. CONCLUSIONS: The results suggest that findings from previous studies may
      be generalized to a broader population.

PMID- 9640900
TI  - Brief report: an intervention program for parents of pediatric cancer patients: a
      randomized controlled trial.
AB  - OBJECTIVE: To evaluate a psychoeducational intervention program for parents of
      pediatric cancer patients, using cognitive and behavioral techniques. METHODS:
      Parents were randomly assigned to an intervention (n = 39) and a control
      condition (n = 42). Baseline assessment took place at diagnosis. Short-term
      effects were measured immediately after the intervention, long-term effects six
      months later. Control parents received standard care. Intervention parents
      received, in addition, a manual-guided program during the first six months
      following the diagnosis. RESULTS: With time all parents became significantly less
      psychologically distressed. However, no between-group differences were noted in
      psychological functioning, satisfaction with support, and intensity of emotions
      immediately postintervention and six months later. CONCLUSIONS: Although the
      clinical evaluation of the intervention was positive, it appeared that a
      structured intervention program as described in this study was not any more
      effective than standard care.

PMID- 9640901
TI  - Consumer bill of rights ordered.

PMID- 9640902
TI  - Acute aortic insufficiency.

PMID- 9640903
TI  - The proposed tobacco settlement is not a good deal.

PMID- 9640904
TI  - Barriers to cardiac transplantation in idiopathic dilated cardiomyopathy: the
      Washington, DC, Dilated Cardiomyopathy Study.
AB  - Although cardiac transplantation offers prolonged survival and improved quality
      of life to patients with end-stage heart failure, many patients with idiopathic
      dilated cardiomyopathy do not undergo this procedure. Possible barriers to
      cardiac transplantation were examined among 138 patients with idiopathic dilated
      cardiomyopathy from five hospitals in Washington, DC. Patients underwent follow
      up for approximately 5 years. The patients or a close family member were
      interviewed at baseline about socioeconomic factors and medical history. The
      patients or their next-of-kin were recontacted at 1-year intervals to determine
      patients' vital status and to obtain information about cardiac transplantation.
      Overall, the cumulative survival at 12 and 60 months was 75.8% and 37.3%,
      respectively. Only 3.6% (5 of 138) of the patients underwent cardiac
      transplantation, and 19 (13.8%) patients had been placed on a waiting list for a
      heart transplant. Black race and nonmarried status were inversely associated with
      cardiac transplantation. Factors associated with not having been placed on a
      waiting list included older age, lower income, and lack of private health
      insurance. Black race was found to be significantly, but inversely associated
      with cardiac transplantation while older age was inversely associated with having
      been placed on a waiting list after adjusting for sex, race, education, and
      private insurance. These findings suggest that black patients with idiopathic
      dilated cardiomyopathy are less likely to undergo cardiac transplantation.

PMID- 9640905
TI  - Physicians and nursing home care.
AB  - Historically, physicians have not played a prominent role in the care of older
      adults who reside in nursing homes. Physicians have been criticized for
      abandoning their responsibilities to nursing home residents since the industry's
      rapid growth in the 1960s, following the enactment of Medicare and Medicaid. As
      many as 72% of private physicians do not go to nursing homes. This is true even
      of those family doctors and internists whose practices are disproportionately
      devoted to the elderly. Caring for institutionalized elderly patients over the
      long term presents challenges that even physicians experienced with geriatric
      patients in the community may find daunting. This study investigates reasons why
      physicians in the Los Angeles area hesitate or refuse to see nursing home
      patients.

PMID- 9640906
TI  - The effectiveness of intermittent hyperbaric oxygen in relieving drug-induced HIV
      associated neuropathy.
AB  - This 3-month study evaluated the effects of hyperbaric oxygen on drug-induced
      neuropathies in 22 patients with human immunodeficiency virus. All patients
      included in the study had been taking an antiretroviral medication for at least
      12 months and had subjective symptoms of numbness or tingling, lethargy, and a
      decrease in deep tendon reflex. Patients with an active substance abuse history
      or Kaposi's sarcoma were excluded. Of the 20 patients who completed the series,
      17 had significant improvement, 2 had a demyelinating disorder that may have
      affected the outcome, and 1 had no change.

PMID- 9640907
TI  - Social support among African-American adults with diabetes. Part 1: Theoretical
      framework.
AB  - Diabetes mellitus affects African Americans in disproportionate numbers relative
      to whites. Proper management of this disease is critical because of the increased
      morbidity and mortality associated with poor diabetes management. The role of
      social support in promoting diabetes management and improved glycemic control
      among African Americans is a little-explored area. This article, the first in a
      two-part series, provides a theoretical framework for examining the relationship
      between social support and glycemic control among African-American adults.

PMID- 9640908
TI  - A characterization of older AIDS patients in Maryland.
AB  - This retrospective study evaluated Maryland acquired immunodeficiency syndrome
      (AIDS) patients who were > or = 50 years at the time of AIDS diagnosis. All
      patients diagnosed between January 1987 and June 1996 who were > 50 years were
      included in the cohort. A total of 610 male (82.7%) and 128 female (17.3%) AIDS
      patients aged > or = 50 were identified. The most common mode of human
      immunodeficiency syndrome (HIV) transmission was male-to-male sexual contact
      (34.7%). Additionally, 146 (19.8%) patients contracted HIV through blood
      transfusions, 93 (12.1%) were infected through heterosexual contact, 134 (18.6)
      were infected through i.v. drug abuse, and the remaining 109 (14.8%) had unknown
      risk factors. Data from this preliminary study demonstrate that an alarming
      percentage of AIDS patients (approximately 10%) in Maryland are aged > or = 50.
      Sexual contact, either male-to-male or heterosexual transmission, was the route
      of transmission for nearly 47% of this patient population. However, few research
      projects, educational programs, or public health initiatives are specifically
      targeted to this patient population. The increasing life expectancy of AIDS
      patients as well as the advent of new drug treatments highlights the need for
      further research to investigate the diagnosis and treatment of AIDS and HIV
      infection among older patients.

PMID- 9640909
TI  - Occult uterine rupture: role of ultrasonography.
AB  - This article presents a case of occult spontaneous uterine rupture complicated by
      pelvic infection and peritonitis in the postpartum period. Ultrasonography played
      a primary role in the diagnosis of this complication and clearly demonstrated the
      uterine wall defect. This finding was confirmed later by computed tomography and
      by surgery.

PMID- 9640910
TI  - Lincoln's last legacy: a narrative of the president's obscured autopsy
      instruments.

PMID- 9640911
TI  - [Angina pectoris is an expensive national disease. It requires a reasonable
      distribution of responsibility between outpatient and inpatient care].

PMID- 9640912
TI  - [Inadequate handling of stress is a risk factor in brain disease. Deviations in
      stress levels can explain unfavourable prognosis].

PMID- 9640913
TI  - [Anorexia--high priority in mass media, not in health care].

PMID- 9640914
TI  - [Are Jews and Muslims in Sweden barbarians?].

PMID- 9640915
TI  - [The link between exposure to mould and respiratory problems is
      incontrovertible].

PMID- 9640916
TI  - [The Kola peninsula: epidemics, high infant mortality, alcoholism...Hard reality
      drains the very small resources of health care].

PMID- 9640917
TI  - [How many X-ray examinations do patients tolerate? The National Institute of
      Radiation Protection's conclusions on the level of knowledge].

PMID- 9640918
TI  - [More strict Swedish rules on radiation protection. New directives from the EU
      for health care].

PMID- 9640919
TI  - [Documented effects of SSRI preparations in anxiety].
AB  - The article consists in a review of the clinical evidence for treating anxiety
      disorders with selective serotonin re-uptake inhibitors (SSRIs). Sufficient
      documentation now exists to support the use of SSRIs in treating panic and
      obsessive-compulsive disorders, and in Sweden moclobemide is now approved for use
      in treating social phobia, and buspirone for use in treating generalised anxiety
      disorder. Further documentation of the treatment of post-traumatic stress
      disorder with SSRIs is probably to be expected. Benzodiazepines remain the most
      commonly used anxiolytics. Although persistent adverse sexual reactions, and
      withdrawal symptoms upon abrupt termination of medication, are notable side
      effects of SSRIs, patients become measurably more self-confident and focused, and
      manage risks more adequately. This underscores the need of further research into
      the interrelationship of personality traits and anxiety symptoms.

PMID- 9640920
TI  - [Forensic psychiatry in Vaxjo and Sundsvall: a new estimation method for unified
      risk assessment].

PMID- 9640921
TI  - [Rehabilitation and prevention. The patient himself actively works to reach the
      targets].

PMID- 9640922
TI  - [Gustaf Billqvist, a physician before his time: "Children must be comfortable in
      hospital to recover!"].

PMID- 9640923
TI  - [Plasma metanephrine measurements make the diagnosis of pheochromocytoma easier].
AB  - A study where plasma metanephrine and normetanephrine concentrations in 51
      patients with hypertension and 62 healthy normotensives were compared with those
      in 52 patients with histologically confirmed phaeochromocytoma showed measurement
      of the two variables to constitute a test that reliably excludes the presence of
      phaeochromocytoma in cases where both values are normal. Other currently
      available tests (e.g., plasma catecholamine assay) can yield false-negative
      results in some patients with the tumour, and thus do not reliably exclude its
      presence in unaffected patients. Accordingly, as a missed diagnosis can have
      disastrous consequences for the patient, hitherto the exclusion of
      phaeochromocytoma has typically entailed multiple and repeated tests which are
      time-consuming and costly. The advantage of the plasma metanephrine
      normetanephrine test is that, as it does not yield false-negative results, a
      negative test result reliably excludes the presence of phaeochromocytoma in
      suspected cases, and no further tests are necessary.

PMID- 9640924
TI  - ["Alcolock"--an effective technique against traffic accidents].

PMID- 9640925
TI  - [How does patient-oriented research work?].

PMID- 9640926
TI  - [When the professional becomes personal. A tactful way to treat a sick
      colleague].

PMID- 9640927
TI  - [Inguinal hernia surgery deserves higher status. A new technique makes great
      progress possible].

PMID- 9640928
TI  - [Should general practitioners have possibility to become subspecialists?].

PMID- 9640929
TI  - [Cost-effective use of drugs should be our goal].

PMID- 9640930
TI  - [To compare hospital departments, a tactful procedure-- continuation].

PMID- 9640931
TI  - [No conclusions can be drawn when the material is too small].

PMID- 9640932
TI  - [Oral flora may be the cause of meningitis in lumbar puncture].

PMID- 9640933
TI  - [Discussion about interventions performed on the human body should be possible].

PMID- 9640934
TI  - [Fluid can be administered via a tube in acute diarrhea in children].

PMID- 9640935
TI  - [A new therapeutic program in advanced ovarian cancer. Good results with
      decentralized cytostatic therapy].
AB  - A trial of decentralised cytostatic (carboplatin + cyclophosphamide) treatment of
      advanced ovarian cancer under centralised supervision, carried out in the
      southern health care region, yielded good results. As carboplatin and
      cyclophosphamide cause myelosuppression which is commonly most manifest two weeks
      after treatment, increasing dosage intervals and reducing dosages is often
      necessary. However, compliance with the protocol for increasing dosage intervals
      and reducing dosages was found to be equally good at Lund and at the various
      local clinics. Although no significant difference in survival was found between
      patients treated with carboplatin and cyclophosphamide according to this model
      and patients treated with cisplatin combined with doxorubicin or epirubicin (P =
      0.42), the former protocol is more appropriate for use in the out-patient clinic.

PMID- 9640936
TI  - [Specimen culture from all children in a day care center because of an outbreak
      of streptococcal infection].
AB  - In an outbreak of recurrent group A streptococcal (GAS) pharyngotonsillitis
      between January and February 1997 at a Swedish preschool, involving 58% (11/19)
      of the children and several family members, clinical examination showed few of
      the children to manifest signs and symptoms of tonsillitis. However, throat
      specimens yielded GAS growth of the same T-type in 42% (8/19) of the children and
      in 30% (6/20) of family members, but in none of the staff. Strict hygiene,
      appropriate antibiotic treatment of all culture-positive individuals irrespective
      of symptoms, and non-attendance at the preschool during the first two days of
      treatment promptly terminated the outbreak and there were no cases of recurrence.

PMID- 9640937
TI  - [Genetic factors are often found inl Alzheimer disease. An extensive twin study
      to clarify the heredity-environment relationship].
AB  - Genetic and environmental risk factors are central concerns in dementia research.
      Through twin studies one can study the relative importance of genetic and
      environmental risk factors. One such study, based on the Swedish Twin Registry,
      shows that genetic effects are of considerable importance for developing
      Alzheimer's disease, even late in life, but that environmental factors are also
      important. For vascular dementia, the results indicate that non-genetic factors
      are of primary importance.

PMID- 9640938
TI  - [Too many cases of recurrences after inguinal hernia surgery. New surgical
      methods and better follow-up should remove the shortages].

PMID- 9640939
TI  - [Successively improved prognosis in erythrocyte immunization].
AB  - Prognosis in cases of erythrocyte immunisation has improved continuously over the
      past decades. Morbidity and mortality have been reduced by improvements in
      management, including screening programmes, non-invasive ultrasound evaluation
      and invasive procedures. The article provides an outline of the latest
      developments in the management of erythrocyte immunisation, and several
      controversial issues are discussed, such as antibody screening, strategies for
      the reduction of antibody titres, and the organisation of care.

PMID- 9640940
TI  - [Oral health among immigrants. An increasing need for dental care. Children are a
      high risk group for caries].

PMID- 9640941
TI  - [General practitioners prescribe more and more antidepressive agents. Repeated
      studies of prescriptions in a small municipality].

PMID- 9640942
TI  - [A new therapeutic model in autism. Interdisciplinary habilitation in specialized
      units].

PMID- 9640943
TI  - [Is it the end of scientific truth?].

PMID- 9640944
TI  - Liability to and for employees while attending seminars.

PMID- 9640945
TI  - Preventing claims in outpatient care environments.

PMID- 9640946
TI  - Physician community involvement. Working within your area to promote better
      health.
AB  - How many times have you been asked to participate in a meeting, forum, or task
      force to address a community health issue in the last few years? Opportunities
      seem to crop up almost weekly as non-profit organizations acclimate to meet
      changing needs and health systems continue to adapt to market forces. But
      participating in ongoing community projects, or even attending periodic meetings,
      draws time away from practice and professional obligations and limits an already
      modest supply of personal time. Is involvement in a community collaborative
      effort worth the time? And, if so, what are the benefits and challenges to
      physicians, health systems, and communities from this type of investment?

PMID- 9640947
TI  - New classes for office staff. MSMS Educational Program focuses on improving your
      practice.
AB  - Have you ever wondered how your practice could benefit from a highly trained and
      specialized office staff? It could improve how patients are treated and enhance
      the day-to-day tasks required to run an office. Medical office personnel are
      essential, and their continued education can directly affect the operation and
      perception of your practice.

PMID- 9640948
TI  - How could alternative therapies affect your practice?

PMID- 9640949
TI  - "Gearing up" for summer. Quick tips and biking essentials.
AB  - With any luck, at about the time this appears in print I'll be appearing on the
      street in my favorite part of my fitness program: bicycling. I don't claim to be
      an expert--my family thinks I'm Miguel Indurain because I can ride 20 miles at a
      time, and I think I'm Marco Pantani because I'm short, bald, and good on hills-
      but I've learned a fair amount in my last three years of riding. If you're an
      experienced rider you probably know at least as much as I do, but if you're a
      beginner--or beginning over after a long hiatus, as I did--then I have some
      suggestions for you.

PMID- 9640950
TI  - Marshall Brown, MD. Bringing care to Guatemala.
AB  - Medical equipment that is obsolete to a physician in the United States may be
      considered "a thing of beauty" to a counterpart in a Third World country. So
      declares Marshall Brown, MD, and otolaryngologist from Saginaw. Retired--in
      theory--since 1994, he has devoted much of his time to gathering donations of
      unused and outdated medical equipment for a hospital near Guatemala City,
      Guatemala. In addition, he has seen that the donated supplies are refurbished and
      get to where they're needed--sometimes flying the supplies there himself.

PMID- 9640951
TI  - Batten down the hatches.

PMID- 9640952
TI  - Urban medicine: beyond the stereotype.

PMID- 9640953
TI  - Successful hospitalist program in Duluth.

PMID- 9640954
TI  - The case for physician practice management companies. And why they haven't taken
      hold in Minnesota.

PMID- 9640955
TI  - Minnesota's new Rural Health School.

PMID- 9640956
TI  - Administrative simplification rules released.

PMID- 9640957
TI  - Managed care in rural Minnesota. Family physicians' attitudes and perceptions.
AB  - Prepaid managed care medicine has become dominant in urban Minnesota and is
      making its way into the rural setting. This study assesses the attitudes of rural
      family practice physicians in Minnesota toward managed care. A survey, consisting
      primarily of five-point Likert scale statements, was mailed to 798 rural
      Minnesota family practice physicians, with a response rate of 35% (281
      respondents). We tabulated overall responses and made comparisons based on
      practice characteristics and years in practice. Twenty physicians participated in
      a follow-up telephone interview. We also conducted telephone interviews with 10
      representatives from managed care organizations. Both positive and negative
      attitudes toward managed care emerged. Two-thirds of respondents did not feel
      that their time with patients was diminished under managed care. However, 67% of
      respondents felt that managed care organizations had failed to incorporate rural
      patients' specific needs into their policies. Only 7% of respondents felt that
      managed care organizations adequately explained their benefits packages to
      enrollees. Rural family practitioners' apparent disillusionment with current
      managed care models merits the attention of those concerned with medical care in
      rural areas.

PMID- 9640958
TI  - Compliance ... or else!

PMID- 9640959
TI  - Fraud investigations: the heat is on.

PMID- 9640960
TI  - Angiotensin-converting enzyme inhibitor cilazapril suppresses expression of basic
      fibroblast growth factor messenger ribonucleic acid and protein in endothelial
      and intimal smooth muscle cells in a vascular injury model of spontaneous
      hypertensive rats.
AB  - The relationship between the expression of basic fibroblast growth factor (bFGF)
      messenger ribonucleic acid (mRNA) and protein, a potent mitogen for vascular
      smooth muscle cells in vivo, and administration of the angiotensin-converting
      enzyme inhibitor cilazapril, which suppresses smooth muscle cells proliferation
      in denuded arteries, was studied in spontaneously hypertensive rats using the in
      situ hybridization technique and immunohistochemical study. The effect of
      cilazapril on neointimal formation through modification of bFGF expression was
      evaluated using the increased tissue expression of the renin-angiotensin system
      in spontaneously hypertensive rats. Arterial injury was produced by using balloon
      catheter denudation in the left carotid artery of rats. The effects were
      evaluated 2 weeks later. bFGF mRNA and protein were observed only in the
      endothelial cells of sham-operated rats. bFGF mRNA and protein were observed in
      both endothelial cells and intimal smooth muscle cells in operated rats receiving
      only vehicle. Expression of bFGF mRNA and protein was suppressed in both
      endothelial cells and intimal smooth muscle cells of operated rats receiving
      cilazapril. These data suggest that cilazapril suppresses smooth muscle cell
      proliferation through modification of the expression of bFGF mRNA and bFGF
      protein in addition to other genes.

PMID- 9640961
TI  - Microsurgical treatment of intramedullary spinal cord tumors.
AB  - Eighty patients with intramedullary spinal cord tumors were treated by
      microsurgical methods between 1988 and 1996. Twenty-nine patients were diagnosed
      with astrocytoma, 36 with ependymoma, five with metastasis, four with lipoma,
      three with dermoid or epidermoid tumor, two with neurofibroma, and one with
      neuroma. Vascular and infectious lesions (such as abscesses and
      hemangioblastomas) were excluded. After laminectomy, total removal of the lesion
      was achieved in 68 of 80 patients and subtotal removal in 12. Postoperative
      radiation therapy was performed in 13 of 80 patients. The follow-up period ranged
      from 12 to 92 months (mean 42.2 months). All patients underwent preoperative and
      postoperative magnetic resonance imaging at intervals ranging from 3 months to 5
      years postoperatively. Four patients showed clinical and radiological evidence of
      local tumor recurrence during the follow-up period. Four patients died 5 months
      to 15 months postoperatively from the re-expansion of their primary metastatic
      disease. The operative results at long term (after the 6th postoperative month)
      were better than the results at short term (before the 6th postoperative month)
      and revealed clinical improvement in 63, no change in 10, and deterioration in
      seven patients. We recommend early radical surgery, whenever possible, to be
      performed when the patient's neurological status is still good. Subtotal removal
      and irradiation are better for malignant or metastatic tumors. Partial
      decompressive removal is best for large intramedullary lipomas. Plastic
      laminotomy with preservation of the intervertebral joints is especially
      recommended in young or middle-aged patients.

PMID- 9640962
TI  - Extensive edema in the thalamus caused by thrombosed basilar artery aneurysm.
AB  - A 69-year-old female presented with sudden onset of truncal ataxia, urinary
      incontinence, mental confusion, and Parinaud's sign. With conservative treatment,
      her ataxia and urinary incontinence resolved. Magnetic resonance (MR) imaging
      disclosed a round mass with laminated intramural hemorrhage in the third
      ventricle. Right vertebral angiography demonstrated a giant aneurysm in the
      distal basilar artery. Xenon-enhanced computed tomography showed that cerebral
      blood flow (CBF) was reduced in the thalamus bilaterally and was paradoxically
      decreased by acetazolamide. Two months later, MR imaging showed that the
      intramural hemorrhage had shrunk, and the edema in the thalamus was resolving.
      The CBF reduction and vascular response to acetazolamide had reversed to some
      extent. A partially thrombosed giant aneurysm can grow acutely as the result of
      fresh intramural hemorrhage. The edema is secondary to ischemia and loss of
      vasoresponsivity.

PMID- 9640963
TI  - Central neurocytoma presenting with intratumoral hemorrhage 15 years after
      initial treatment by partial removal and irradiation.
AB  - A 50-year-old male presented with a central neurocytoma with intratumoral
      homorrhage. He had undergone partial removal of the tumor and postoperative
      radiation therapy 15 years previously. He was followed as an outpatient after the
      initial treatment, and there was no evidence of regrowth of the residual tumor.
      Removal of the hematoma and biopsy of the tumor were performed. Abnormally
      developed blood capillaries in the tumor may have undergone disturbances of
      circulation caused by irradiation which resulted in bleeding. Patients with
      partially resected central neurocytomas which have low proliferative potential
      may not require radiation therapy, due to the benign nature and the risk of
      delayed complications of irradiation including intratumoral hemorrhage.

PMID- 9640964
TI  - Pilocytic astrocytoma of the velum interpositum.
AB  - A 72-year-old male presented with a pilocytic astrocytoma in the velum
      interpositum manifesting as a 5-day history of dizziness attacks and unstable
      gait. Computed tomography and T1-weighted magnetic resonance imaging with
      gadolinium enhancement demonstrated a small, homogeneously enhanced mass in the
      velum interpositum. The tumor was removed subtotally, and the structure of the
      splenium was intact. The histological diagnosis was pilocytic astrocytoma. The
      MIB-1 growth fraction was 5%. The tumor may have originated from the splenium or
      the thalamus. The aggressive histology indicates the need for close neuroimaging
      follow-up.

PMID- 9640965
TI  - Glioblastoma following radiotherapy in a patient with tuberous sclerosis.
AB  - A 26-year-old male with tuberous sclerosis developed a glioblastoma in the right
      temporal lobe 8 years after surgical excision and irradiation of a subependymal
      giant cell astrocytoma. The glioblastoma was probably an irradiation-induced
      tumor. Irradiation should not be given routinely for subependymal giant cell
      astrocytoma.

PMID- 9640966
TI  - Plasma cell granuloma extending from the extracranial to the intracranial space
      associated with Epstein-Barr virus infection.
AB  - A 70-year-old male presented with a plasma cell granuloma extending from the
      extracranial to the intracranial space. Findings of preoperative magnetic
      resonance imaging and intraoperative observation indicated that the lesion
      extended from the temporal muscle to the subarachnoid space, penetrating the
      frontal bone. The subarachnoid lesion was composed of neutrophils indicating the
      presence of acute or subacute inflammation. The final diagnosis of the resected
      tumor was plasma cell granuloma. High levels of antibodies against Epstein-Barr
      (EB) virus in the cerebrospinal fluid and the immunohistochemical demonstration
      of EB nuclear antigens in the plasma cell granuloma suggested that EB virus
      infection was associated with the development of plasma cell granuloma in this
      patient.

PMID- 9640967
TI  - Pineal dermoid cyst developing 18 years after gross total removal of a pineal
      mature teratoma.
AB  - A 21-year-old male presented with a pineal dermoid cyst manifesting as headache
      and diplopia. He had undergone gross total removal of a pineal mature teratoma 18
      years before and had done well until recently. Diffusion-weighted magnetic
      resonance imaging showed a region of high signal intensity due to a round mass in
      the pineal region and extending into the trigone of the right lateral ventricle.
      Subtotal excision of the tumor was achieved. Histological examination showed an
      epidermoid cyst consisting of keratinized stratified squamous epithelium and
      connective tissue. Intraoperative observation had detected black hairs, so the
      diagnosis was dermoid cyst. The dermoid cyst may have arisen from a microscopic
      remnant of the cyst wall of the original pineal mature teratoma. The regrowth of
      a dermoid cyst 18 years after gross total removal of a mature cystic teratoma in
      the pineal region is exceptional. However, careful follow-up of patients who
      undergo gross total removal of a pineal teratoma is recommended for a period more
      than that of the patient's age at surgery plus 9 months.

PMID- 9640968
TI  - Theodor Kocher, Hayazo Ito, and Harvey Cushing in Berne, Switzerland.

PMID- 9640969
TI  - ECL cells involvement in the isoproterenol-induced gastroprotection. An
      ultrastructural study.
AB  - The central and peripheral adrenergic systems are involved in the regulation of
      several functions in the gut including the maintenance of gastric
      microcirculation and gastric secretion but little is known about the role of the
      adrenergic system, in particular, beta-adrenoceptors in the phenomenon of
      gastroprotection. In this study acute gastric lesions were provoked by an
      intragastric (i.g.) application of 100% ethanol in rats with topical application
      of isoproterenol (ISO) (1 mg/kg) or subcutaneous (s.c.) administration of
      ranitidine (RAN) (40 mg/kg) or both. An area of gastric lesions was determined by
      planimetry, gastric blood flow (GBF) was determined by H2-gas clearance technique
      and gastric specimens were taken for histology and electron microscopy. It was
      found that ISO reduced ethanol-induced gastric mucosal lesions and this effect
      was accompanied by a rise in GBF. In contrast, RAN applied s.c. in a dose that
      produced almost complete achlorhydria, failed to affect ethanol-lesions but
      attenuated significantly ISO induced gastroprotection and abolished the increase
      in the GBF induced by this beta-adrenoceptor agonist. Histology and
      ultrastructural study revealed that pretreatment with ISO influenced HCl
      production reflected by the elaborated secretory surface of parietal cell
      intracellular canaliculi. All these changes were accompanied by the
      ultrastructural changes in Golgi apparatus in ECL-like cells (histamine storing
      cells). Pretreatment with ISO caused the collapse of Golgi profiles and only
      peripheral sacs were not compressed but such a change was not observed after RAN
      treatment. The best developed Golgi was, however, seen in the control rats
      without any treatment. Secretory granules in ECL cells were significantly
      expanded after pretreatment with ISO but did not show significant morphological
      changes in rats pretreated with RAN. We conclude that 1. ISO protects the gastric
      mucosa injured by ethanol presumably due to increased gastric microcirculation,
      and 2. ECL-like cells are actively involved in ISO-induced gastroprotection
      possibly by the increased histamine release which is reflected by ECL-cell and
      Golgi apparatus morphology.

PMID- 9640970
TI  - Immunohistochemical status of p53, mdm2 and Ki-67 in malignant fibrous
      histiocytoma.
AB  - The aim of the study was to evaluate the frequency of p53, mdm2 and Ki-67
      immunopositivity in MFH, and to investigate possible associations of their
      expression with the grade of malignancy and predominant histological pattern-
      storiform, pleomorphic and myxoid subtype of MFH. A total number of 51 tumor
      samples from 21 primary and 30 secondary MFHs was studied using monoclonal anti
      p53 (DO-78, DAKO), anti-mdm2 (1F2, NOVOCASTRA) and polyclonal anti-Ki-67 (DAKO)
      antibodies. The p53 immunopositivity was observed in 32.7% of all tumor samples
      (in 36.8% of primary and in 30% of recurrent and metastatic tumors). The mdm2
      immunopositivity was noted in 34.8% of all tumor samples (in 33.3% of primary and
      35.7% of secondary tumors). The mean percentage of p53, mdm2 and Ki-67 positive
      cells was 15.5, 8.8 and 7.05, respectively. The mean Ki-67 LI was statistically
      higher in grade 3 than in grade 2 of malignancy (p = 0.006). A significant
      correlation was found between mdm2 positivity and histological subtypes of MFH-
      storiform and pleomorphic types were more frequently mdm2 positive than myxoid
      variant (p = 0.035 and p = 0.009, respectively). No such correlation was observed
      for p53 positivity of tumors and subtypes, but there was a statistically
      significant difference in the percentage of p53 positive cells between storiform
      and myxoid type (p = 0.049). We also noted more tumors expressing high percentage
      (over 20%) of mdm2 positive cells in pleomorphic and storiform subtypes than in
      myxoid variant (p = 0.048). The Ki-67 LI was also higher in pleomorphic than in
      other types of MFH (p = 0.012). A strong positive correlation was found between
      p53 positivity and mdm2 positivity of tumors in primary MFHs (p = 0.00146). p53
      and mdm2 positive tumors were mainly in grade 3 of malignancy, but no
      statistically significant correlations were noted. A positive correlation between
      the percentage of p53 positive cells and Ki-67 positive cells (p = 0.0028) was
      observed.

PMID- 9640971
TI  - Glomerular basement membrane thickness in minimal change disease. The
      ultrastructural quantitative study.
AB  - Fifteen renal biopsy specimens from adult patients with minimal change disease
      (MCD) for whom both light and electron microscopy as well as immunofluorescence
      microscopy and full clinical data were available were examined quantitatively and
      compared with six normal controls. The electron micrographs of the glomeruli were
      scanned in Primax flatbed A4 scanner and then morphometric investigations were
      performed by means of a computer image analysis system to compare glomerular
      basement membrane (GBM) thickness and to study whether this parameter could
      correlate with the degree of proteinuria. The study revealed that the mean GBM
      thickness was lower in MCD patients as compared with normal controls (299.2 nm
      versus 338.8 nm), but this difference did not reach statistical significance.
      Interestingly, the present investigations showed that the GBM thickness tended to
      be related directly to proteinuria and not inversely as it might be expected, but
      this relationship was not significant, either. In conclusion, we can confirm the
      tendency to GBM thinning in adult MCD patients. It should be also noted, that GBM
      thinning did not increase the degree of proteinuria in these cases.

PMID- 9640972
TI  - Tracheobronchial amyloidosis.
AB  - The authors have described eleven cases of tracheobronchial amyloidosis, in 6 men
      and 5 women with a mean age of 58.7 years. The follow-up period ranged from
      several month to six years. The clinical picture and histopathological changes in
      bronchoscopic and postmortem sections in two patients were described. In all
      cases immunohistochemical examinations for the presence of amyloid AA, AL,
      transthyretin (prealbumin) and beta 2-microglobulin were performed. In six cases
      the presence of transthyretin was found. The remaining reactions were negative.
      Resorptive giant cells reaction to amyloid was observed in 3 transthyretin
      positive cases and 1 transthyretin negative case. Four cases with negative
      amyloid in the examination for the presence of transthyretin accompanied
      bronchial carcinoma, all these cases were men with a mean age of 63.0 years.

PMID- 9640973
TI  - NSAIDs associated nephropathy.
AB  - Renal biopsy of 32 patients who developed renal complications after treatment
      with nonsteroidal anti-inflammatory drugs (NSAIDs) were studied. The treatment
      with NSAIDs in these cases was used for many reasons such as: headaches,
      toothaches, dysmenorrea, osteochondrosis, polyarthritis and acute respiratory
      infections. The renal function of these patients, before the treatment with
      NSAIDs was normal. The renal biopsies were studied by light, electron and
      immunofluorescence microscopy. In 32 cases treated with NSAIDs renal changes were
      shown. There types of morphological changes were found: focal glomerulonephritis
      with crescents (FGN)(5 cases), acute tubulo-interstitial diseases (ATID)(8 cases)
      and lipoid nephrosis with tubulo-interstitial nephritis (LN)(19 cases). FGN and
      ATID possibly represent a hypersensitive reaction of predominantly humoral (FGN)
      or cellular (ATID) mechanisms. These types of reaction are also seen to occur
      with the use of various drugs (most commonly with penicillin type antibiotics).
      LN on the other hand is rarely, if ever, seen with any drugs but NSAIDs and
      therefore seems to be a characteristic change for NSAIDs and possibly related to
      the inhibition of renal prostaglandin synthesis by NSAIDs. NSAIDs-associated
      renal dysfunction is mainly observed in patients of an increased use of NSAIDs
      with ineffective circulatory plasma volume (advanced age, cardiovascular disease,
      overweight and hypovolemia of various causes).

PMID- 9640974
TI  - A cytotelepathology consulting station.

PMID- 9640975
TI  - Primary intrapericardial malignant fibrous histiocytoma. A case report.
AB  - A case of giant intrapericardial malignant fibrous histiocytoma has been
      reported. A brief review of primary cardiac tumours has been presented taking
      into account differential diagnosis of neoplasms of histologically myxomatous
      nature.

PMID- 9640976
TI  - [Fc gamma receptors in human placenta].
AB  - This review summarizes the status of our knowledge on the structure, expression
      and function of Fc gamma R in the placenta. The discovery in syncytiotrophoblast
      of an MHC class I--related FcR, of the type responsible for intestinal uptake of
      milk IgG in suckling rats and mice is also described.

PMID- 9640977
TI  - [Soluble IL-6 receptors].
AB  - Both subunits of IL-6 membrane--associated receptor, IL-6R and gp130 can exhibit
      in a soluble forms--sIL-6R and sgp130 respectively. Soluble IL-6 receptor (sIL
      6R) can bind IL-6 and mediate IL-6 function through association with gp130 which
      is the signal transducing protein. In contrast to other receptors, sIL-6R has a
      potential to enhance the IL-6 biological function. sIL-6R and sgp130 were found
      in appreciable amounts in body fluids, although the exact cellular source and
      function of these proteins are not completely clear.

PMID- 9640978
TI  - [TNF-alpha preactivation (priming) of neutrophils--effect on selected neutrophil
      functions].
AB  - Human polymorphonuclear cells (neutrophils) are fundamentally protective, but
      extracellular release of proteolytic enzymes and oxygen radicals may lead to
      tissue destruction. Granulocyte function can be rapidly amplified by
      environmental factors through a mechanism termed "priming". Priming enhances the
      neutrophils' ability to respond to a secondary agonist, with increased adhesion,
      respiratory burst, and degranulation. This review summarizes the effects of TNF
      alpha priming on the neutrophils' function.

PMID- 9640979
TI  - [Controlled release antigen from the injection site--new model for a single-shot
      vaccination?].
AB  - Continuously increasing number of available vaccines and a wide use of mass
      vaccination campaigns lead to the development of simpler methods of vaccine
      delivery. There is the WHO-sponsored project, including several scientific
      groups, which aims to reduce the number of repeated administrations of vaccines
      required for long-term protection and to obviate the need for booster
      immunization. Such a task may be achieved by the use of controlled-release
      parenteral systems. One such delivery system comprises microspheres constructed
      from biodegradable, biocompatible polymers based on poly lactic/glycolic acid.
      Recent developments of a single-shot tetanus toxoid, encapsulated in the
      biodegradable polymeric microspheres or microcapsules are reviewed. There are
      promising advances in the WHO-sponsored project. However, further efforts are
      needed to elaborate an affective late release of antigen and to obtain a strong
      booster effect in vaccinated animals.

PMID- 9640980
TI  - [Wound repair].

PMID- 9640981
TI  - [Metabolites of arachidonic acid (eicosanoids) in the airways--the role of
      epithelium in synthesis of eicosanoids].
AB  - Arachidonic acid metabolites are potent modulators in physiology and mediators in
      pathophysiology of airways. They play important role in allergic diseases. There
      are two main sources of eicosanoids found in nasal and bronchial lavages: airway
      epithelial cells and influx cells. Authors described spectra of eicosanoids
      produced by epithelial cells in vitro and compare them with in vivo findings. The
      review of similarities and differences between arachidonic acid metabolism in
      human upper and lower airways is also included.

PMID- 9640982
TI  - [Body dysmorphic disorder: clinical picture, diagnostic criteria, prevalence,
      course and treatment].
AB  - The article presents historical conceptions of dysmorphphobia and a review of
      recent references concerning aetiology, criteria for diagnosis of this disorder
      in new classifications of mental disorders (DSM-IV and ICD-10), course, and
      proposition of treatment. The author described characteristic personality traits
      of patients with dysmorphophobia and mental disorders, which are very often
      comorbid with this disorder (obsessive-compulsive disorder, phobia, delusional
      disorder-somatic type) and mental disorders in first-degree relatives of persons
      with dysmorphophobia.

PMID- 9640983
TI  - [Results of long-term observation (3-11 years) of patients with dual diagnosis:
      body dysmorphic disorder and delusional disorder, somatic type].
AB  - This work presents results of a retrospective and prospective research of 15
      persons with a double diagnosis: body dysmorphic disorder, and delusional
      disorder, somatic type. It was established that these disorders starting in
      adolescence, occurred in persons who earlier had traits of avoidant and obsessive
      compulsive personality or social phobia. In most subjects with dysmorphophobia
      there was comorbidity of dysthymia or major depression. An improvement in the
      state of these patients, most often after implementation of complex therapeutic
      measures: psychotherapy as well as pharmacotherapy with neuroleptic and SSRI's or
      clomipramine has to do with withdrawal of delusions, whereas the symptoms of body
      dysmorphic disorder usually last for years. In some patients delusional disorders
      had a tendency to reoccur or to be chronic, and lead to a considerable impairment
      of social functioning.

PMID- 9640984
TI  - [Liaison between body dysmorphic disorder and eating disorders].
AB  - This study presents the cases of anorexia nervosa which began with a body
      dysmorphic disorder lasting for at least 6 months. In some subjects (25%) there
      was comorbidity of 3 mental disorders: anancastic personality or obsessive
      compulsive disorder + dysmorphophobia + anorexia nervosa or dysmorphophobia +
      anorexia nervosa + depressive disorder (dysthymia or major depression). The
      author considers the conception that in some cases dysmorphophobia and anorexia
      nervosa are a spectre of obsessive-compulsive disorder or affective disorders in
      adolescents.

PMID- 9640985
TI  - [Multifactorial aspects of eating disorders].
AB  - A group of patients (52 women and 3 men) aged 12-39 with the diagnosis of
      anorexia nervosa (51 persons) and bulimia nervosa (4 persons) treated in the I
      Psychiatry Department of Medical University of Gdansk between 1972-1994 was
      studied. The diagnostic criteria were in accord with the DSM-IV. Among anorectic
      patients 45 persons were of restricting type and 6 were of bulimic type. Duration
      of illness was 1-14 years. Most of the patients were still students. Analysis of
      the aspects of eating disorders showed family conflict situations, single
      parents, conflicts between parents, competition at home. The patients presented
      fearful attitude, egocentrism, problems with acceptation of the gender role,
      obsessive-compulsive traits. In 36.7% cases minimal brain damage symptoms were
      found. Statistically significant weight gain was observed after neuroleptic
      treatment.

PMID- 9640986
TI  - [The influence of early childhood experiences on depression among medical
      students. Preliminary study].
AB  - The aim of this study was an attempt to estimate depression prevalence in medical
      students. Simultaneously we tried to asses the impact of early negative
      experiences on the level of depression in that population. We examined 92 third
      year medical students of the Silesian Academy of Medicine (54 women and 38 men)
      at the age from 20 to 24. Frequency and intensification of depression were
      assessed by using Beck Depression Inventory. Early experiences including negative
      and positive ones were estimated with the use of a self prepared repertory test
      called "biographical path", based on Personal Construct Theory of George Kelly.
      The obtained results indicated that 25% of examined students had depression
      symptoms. These students were exposed more frequently to early negative
      experiences than students without depression. In childhood depressive students
      were under pressure of their environment to score successes. If they did not
      realise these expectations they were exposed to discontent and frustration of
      their parents. Depressive students came less frequently into contact with other
      people and acquired independence later than non depressive students.

PMID- 9640987
TI  - [Memory processes in endogenous depression].
AB  - The thesis aims to answer the questions about the profile of mental ability in
      endogenous depression and to decide whether self-estimation of depressive
      symptoms influences the results achieved by patients in memory tests. Fifty six
      patients suffering from endogenous depression have been examined. The following
      methods have been applied: Mini Mental State Examination, Benton Visual Retention
      Test, Beck Depression Inventory, hold tests: Vocabulary, Information,
      Comprehension and Digit Span of Wechsler Adult Intelligence Scale (WAIS), Rey
      Osterrieth Complex Figure, Auditory Verbal Learning Test, DCS Weidlich. General
      status of cognitive functions correlates with the profile of specific kinds of
      memory results, particularly with delayed memory. Self-estimation of depressive
      symptoms intensity is mostly influenced by memory capacity, visuomotorial factor,
      functions of perception and lingual factor. High correlation between verbal and
      non verbal learning shows uniform influence of depression on the process of
      learning.

PMID- 9640988
TI  - [Depression in epileptic patients with and without history of suicidal attempts:
      preliminary report].
AB  - Depression is a significant problem in epilepsy. Suicides occur in epileptic
      patients five times more often than in general population. Material included 34
      epileptics with 76 suicidal attempts and 24 patients with no history of suicide.
      Psychical state was studied with Beck Depression Inventory and Hamilton
      Depression Rating Scale. In the group with suicidal attempts 65% of patients had
      depression (54.5% of them had major depression) and in group without suicide
      attempts depression was noted in 54% (23% with major depression). Patients with
      depression were divided into two groups: group I with suicidal attempts and group
      II without history of suicide. In group I more patients were alcohol abusers (50%
      vs 31%), more were treated because of epilepsy longer than 10 years (59% vs 46%)
      and more had tonic-clonic seizures (82% vs 46%). In group I, 54% of patients were
      on polytherapy (more than half of them with fenobarbital). In group II, 31% of
      epileptics were on polytherapy (no one with fenobarbital). Major depression was
      significantly more frequent in epileptics with suicidal attempts. The severity of
      depression may influence the risk of suicide. Major depression may be associated
      with late age of onset of epilepsy, longer treatment duration, tonic-clonic
      seizures, polytherapy (mainly with fenobarbital) and alcohol abuse.

PMID- 9640989
TI  - [Carl Wernicke's school of neuropsychiatry in Wroclaw].

PMID- 9640990
TI  - [Alois Alzheimer's traces in Wroclaw].

PMID- 9640991
TI  - Summary of a National Institute of Mental Health workshop on late-life anxiety.

PMID- 9640992
TI  - The acute and chronic performance effects of alprazolam and lorazepam in the
      elderly: relationship to duration of treatment and self-rated sedation.
AB  - We examined the acute performance and sedative effects of single high and low
      doses of alprazolam and lorazepam, both before and after chronic, 3-week b.i.d.
      treatment in elderly adults. The effects of chronic treatment also were examined
      in this parallel, double-blind, placebo-controlled study. Initial acute low doses
      significantly impaired total recall and increased intrusion errors. High doses
      also impaired delayed recall and critical flicker fusion threshold (CFF). Only
      chronic treatment with high-dose alprazolam increased intrusions and self-rated
      sedation. Single-dose rechallenge after chronic treatment was associated with
      significantly less impairment than the initial challenge in memory tasks but not
      in the discriminant reaction time (DRAT) task. For most memory measures, the
      development of tolerance was only partial; rechallenge still produced significant
      deficits in relation to placebo. The development of tolerance was task-specific
      and depended on drug type and dosage. Despite impairments in various memory
      functions, CFF, and DRAT, volunteers did not report significant drug-induced
      changes in sedation.

PMID- 9640993
TI  - Assessment issues in treatment research of pediatric anxiety disorders: what is
      working, what is not working, what is missing, and what needs improvement.
AB  - Reviewing the strengths and weaknesses of the rating scales for anxiety disorders
      makes it possible to select appropriate measures for use in a multisite treatment
      study of children and adolescents with DSM-IV-diagnosed anxiety disorders.
      Categorical diagnosis for study inclusion is provided by the K-SADS-PL, which has
      strong published psychometrics for anxiety disorders. Broadband symptom ratings
      of diverse pediatric psychiatric disorder can be obtained at baseline by the
      parent-scored Child Behavior Checklist. Anxiety symptom monitoring may be
      provided by the use of two psychometrically strong self-report measures, the MASC
      and the SCARED. Weekly global ratings are provided by the CGI whose scale points
      have been enhanced by detailed anchors; in addition, the raters all trained on
      practice vignettes to calibrate their scoring. Clinician-based ratings of the
      patient's anxiety symptoms can be carried out in adolescent patients using the
      HAM-A. The newly developed Children's Anxiety Rating Scale promises to cover the
      full pediatric age range as a clinician-based anxiety rating instrument, but must
      first be subjected to formal psychometric and treatment sensitivity evaluation.

PMID- 9640994
TI  - Changes on the Temperament and Character Inventory after paroxetine treatment in
      volunteers with generalized anxiety disorder.
AB  - Previously untreated symptomatic volunteers with generalized anxiety disorder
      (GAD) performed the Temperament and Character Inventory at baseline and after 4
      to 6 months of paroxetine treatment. Scores from 29 volunteers were analyzed with
      paired t-tests. A marked reduction was noted in Harm Avoidance and a marked
      increase was noted in Self-Directedness. Smaller changes were noted in
      Cooperativeness and Novelty Seeking. Overall, treatment was associated with a
      reduction in maladaptive personality traits.

PMID- 9640995
TI  - The efficacy of new pharmacological treatments for panic disorder: evaluating the
      trials.

PMID- 9640996
TI  - Pivotal studies of clonazepam in panic disorder.
AB  - Clonazepam has recently been approved for the treatment of panic disorder. Two
      large placebo-controlled efficacy trials were completed; superior benefit was
      found for the drug on most measures. The studies are reviewed in relation to the
      criteria set forth by Shear and Maser with respect to design, diagnostic, and
      outcome measures. Most, but not all, recommended measures were used. Measurement
      of panic attack severity, duration, and frequency were generally the least
      satisfactory of all outcome variables and failed to provide the consistent
      benefit that was found with other measures. A slow discontinuation phase was
      employed, and a benign withdrawal course was noted, although withdrawal from
      higher doses was associated with more emergent symptomatology.

PMID- 9640997
TI  - Efficacy studies of paroxetine in panic disorder.
AB  - The optimal assessment of treatment outcome for studies assessing the efficacy of
      treatments for panic disorder has been a controversial topic. A recent National
      Institute of Mental Health (NIMH)-sponsored consensus conference addressed this
      important topic, and a summary paper regarding assessment of essential elements
      of the disorder resulted. Among other conclusions, it was agreed that several
      different domains should be considered as essential. This article reviews three
      pivotal studies assessing the efficacy of paroxetine for the treatment of panic
      disorder, and evaluates these studies for inclusion of those variables considered
      essential. Additionally, some data were reanalyzed to determine the percentage of
      individuals in these studies who are unequivocal responders (i.e., were both
      panic-free and rated on global assessment as responders). A longer-term treatment
      and relapse study is also mentioned briefly.

PMID- 9640998
TI  - Methodologies and outcomes from the sertraline multicenter flexible-dose trials.
AB  - This article summarizes the results of a combined analysis from two identical
      multicenter clinical trials that investigated the efficacy and safety of
      sertraline versus placebo for treating panic disorder. Patients with panic
      disorder who were treated with sertraline had a statistically significant
      reduction in the mean number of panic attacks per week (the primary efficacy
      measure) as compared with placebo (4.8 vs. 2.5, p < .001). Sertraline-treated
      patients also showed greater improvement that was statistically significant on
      several ratings of panic disorder symptomatology and functioning. The design
      characteristics, clinical rating measures, and outcome measures in these trials
      included most of the features deemed essential by Shear and Maser (1994) in their
      summary of the NIMH Consensus Conference for the development of standardized
      assessments for panic disorder. This suggests that the NIMH Consensus Conference
      played a key role in developing successful multicenter pharmacological treatment
      studies, such as this one that ultimately demonstrated that sertraline was an
      effective treatment for panic disorder.

PMID- 9640999
TI  - Efficacy studies of alprazolam in panic disorder.
AB  - Alprazolam was the first pharmacological agent to be approved for the treatment
      of panic disorder. In seeking that approval, the Upjohn Company conducted the
      earliest large, multicenter drug trials in panic disorder, involving nearly 1,700
      patients in 14 countries. The administrative and quality assurance procedures
      developed for those studies have become a model for subsequent research. Despite
      this history, the efficacy of alprazolam for panic disorder has been contested.
      This article summarizes the published multicenter data from the perspective of
      the assessment criteria recommended by Shear and Maser (1994) and presents
      comparative findings from the Philadelphia maintenance study and the
      London/Toronto study of alprazolam and exposure therapy. Data on relapse
      following treatment discontinuation are also reviewed.

PMID- 9641000
TI  - Commentary: the treatment of panic.

PMID- 9641001
TI  - Long-term experience with clonazepam in patients with a primary diagnosis of
      panic disorder.
AB  - This study examined the use patterns and efficacy of the high potency
      benzodiazepine (HPB) clonazepam in panic patients who were treated and followed
      naturalistically in the Massachusetts General Hospital Longitudinal Study of
      Panic Disorder. Of 204 patients followed over a 2-year period, 46 percent were
      receiving clonazepam alone or in combination with an antidepressant. Treatment
      was not controlled at initial evaluation or during the followup period. The main
      variables assessed in this analysis included global severity of the panic
      disorder and stability of clonazepam dose. All treatment groups tended to improve
      over time without significant differences in outcome between groups. Clonazepam
      doses remained stable over time. Results of this study suggest that treatment of
      panic disorder with the HPB clonazepam achieved and maintained a therapeutic
      benefit similar to that obtained with alternative pharmacologic treatments,
      without the development of tolerance as manifested by dose escalation or
      worsening of clinical status.

PMID- 9641002
TI  - Low-dose venlafaxine treatment in panic disorder.
AB  - Venlafaxine, a structurally novel antidepressant that combines mechanisms of
      action of both the cyclic antidepressants and SSRIs, may be effective in the
      treatment of panic disorder. Thirteen patients with DSM-IV panic disorder with or
      without agoraphobia participated in an open-label, fixed-flexible dose treatment
      study with venlafaxine. All patients who completed the 10-week trial exhibited
      statistically significant decreases in scores on anxiety symptoms as well as
      complete cessation of panic attacks at an effective mean daily dose of 47 mg per
      day. Venlafaxine was well tolerated in all completers. Venlafaxine may be an
      effective antipanic agent, even at lower than typical antidepressant dosages.

PMID- 9641003
TI  - Effect of venlafaxine on the pharmacokinetics of alprazolam.
AB  - Potential pharmacokinetic effects of venlafaxine on alprazolam, a substrate of
      the cytochrome pigment 450 (CYP) isoenzyme CYP3A4, were investigated in 16
      healthy volunteers. A single 2-mg oral dose of alprazolam was combined with
      steady-state levels of venlafaxine administered orally at 75 mg twice daily. The
      levels of alprazolam in plasma and of alprazolam, alpha-hydroxyalprazolam, and 4
      hydroxyalprazolam in urine were determined. Steady-state venlafaxine and O
      desmethylvenlafaxine concentrations in plasma were reached before venlafaxine was
      coadministered with alprazolam. Coadministering venlafaxine increased the
      apparent oral clearance and volume of distribution of alprazolam by 36 percent
      and 9 percent, respectively, and decreased the alprazolam area under the
      concentration-time curve and half-life by 29 percent and 21 percent,
      respectively. There were small but statistically significant increases in mean
      baseline scores for the digit-symbol substitution and symbol copying tests,
      probably reflecting a time-dependent learning effect. The maximum score decrease
      from baseline for these two tests also increased, possibly representing an
      additive effect of alprazolam and venlafaxine. Overall, venlafaxine did not
      inhibit the CYP3A4-mediated metabolism of alprazolam in vivo, which corroborates
      other in vitro and in vivo data showing a lack of CYP3A4 inhibition with
      venlafaxine.

PMID- 9641004
TI  - A controlled trial of venlafaxine in trichotillomania: interim phase I results.
AB  - This article reports the preliminary findings of a two-phase trial examining the
      efficacy of venlafaxine in trichotillomania. Phase 1 is a 12-week, open-label,
      prospective trial of venlafaxine in trichotillomania. Venlafaxine was effective
      in significantly reducing the symptoms of trichotillomania; 8 of 12 patients were
      considered responders. The implications of the efficacy of venlafaxine in
      trichotillomania are discussed, including its important advantages over other
      available antidepressant and anxiolytic medications.

PMID- 9641005
TI  - An open-label pilot study of fluvoxamine for mixed anxiety-depression.
AB  - The syndrome of mixed anxiety and depression (MAD) has been described and is
      familiar to both general psychiatrists and nonpsychiatrists. It was included in
      the DSM-IV appendix as a syndrome proposed for further study. Fluvoxamine, a
      selective serotonin reuptake inhibitor (SSRI) approved for the treatment of
      obsessive-compulsive disorder, was studied for its effectiveness in treating
      anxiety and depression simultaneously during an 8-week, open-label trial of
      patients with MAD. Thirteen patients were included in the final, intent-to-treat,
      analysis. Fluvoxamine showed moderately strong effectiveness in improving anxiety
      and depression with a greater effect on the depressive component. Nausea,
      insomnia, delayed ejaculation, and nervousness were the most common side effects
      reported, with no serious adverse events occurring. Future double-blind placebo
      controlled studies will give more conclusive results.

PMID- 9641006
TI  - Interclass drug effects and changes in regional brain glucose metabolism.
AB  - We have developed an innovative use of positron emission tomography that has
      broad applications in drug development. Based on the FDG method (Phelps et al.
      1979) for assessing glucose metabolism, the method requires rigorous experimental
      control of subjects and standardized data acquisition and analyses. In localizing
      net metabolic drug effects, measured in quantifiable terms, we have derived a new
      conceptual basis for examining pharmacologically induced changes in brain
      function and a new model for predicting drug effectiveness. We applied this
      method to studies of drugs in three different classes and noted marked
      differences in distribution and magnitude of metabolic effects. This approach
      presents an opportunity to selectively examine measurements of the glucose
      metabolic changes induced by specific pharmacological probes on intermediary
      metabolic pathways, including regulation of gene expression and the metabolic
      consequences of neurotransmitter alteration in pharmacologically targeted
      neuronal systems. Development of these methods provides new approaches for
      studying neurobiological mechanisms, and can contribute significantly to the
      process of new drug development.

PMID- 9641007
TI  - [The overshoot of the ST segment during exertion: a sign of the severity of the
      pathology of the coronary arteries].

PMID- 9641008
TI  - [How I treat colorectal cancer. I. Prevention and adjuvant treatment].
AB  - Colorectal adenocarcinoma is a major cause of cancer-related morbidity and
      mortality in Belgium and in other western countries. Prevention implies a
      modification of alimentation and maybe a chronic uptake of acetylsalicylic acid.
      Treatment of colorectal cancers is based on surgery and the prognosis is
      determined by the locoregional or metastatic tumor spread. Complete resection of
      any Astler Coller stage C colorectal malignant tumor has to be followed by a 5
      fluorouracil-based adjuvant chemotherapy. In these protocols, 5-fluorouracil is
      administered together with folinic acid or levamisole. The administration of an
      adjuvant chemotherapy could also be considered for stage BII diseases. As rectal
      cancers are characterized by high local relapse rates, their treatment should
      associate radiotherapy, given either post-surgery or preferentially pre-surgery,
      with resection and chemotherapy. Appropriate treatment of colorectal cancers thus
      requires a concerted multidisciplinary approach.

PMID- 9641009
TI  - [Clinical case of the month. Galloping nephropathy in a patient with type 2
      diabetes].
AB  - We report the case of a patient with insulin-requiring type 2 diabetes who
      exhibited a rapid deterioration of his renal function leading to haemodialysis in
      a few months. Various diagnosis were considered to explain this rapid
      deterioration, excluding diabetic nephropathy as major etiology. The exploration,
      especially renal biopsy, demonstrated the presence of a glomerulonephritis due to
      the deposition of immune complexes associated to active hepatitis C rather than
      diabetic glomerulosclerosis. A treatment with interferon-alpha allowed to
      partially restore renal function, this recovery permitting the interruption of
      hemodialysis, with a current follow-up of more than 6 months.

PMID- 9641010
TI  - [Osseointegrated endosseous implants, University of Liege concepts. Various
      clinical applications].
AB  - Based on fundamental experimental studies performed by the research teams of
      Professor Branemark (Goteborg, Sweden), the use of dental implants has become a
      scientifically accepted treatment concept in Dentistry to replace lost or missing
      teeth in fully and partially edentulous patients. The use of dental implants was
      initiated by the discovery that dental implants made of titanium can be anchored
      in the jawbone with direct bone contact (osseointegration).

PMID- 9641011
TI  - [Dermoscopy: magnified imaging of pigmented cutaneous tumors].
AB  - The early clinical identification of malignant melanoma is important. Pigmented
      neoplasms are sometimes difficult to diagnose by visual inspection alone.
      Dermoscopy increases the reliability of the clinical assessment. Dermoscopic
      criteria of malignancy are well defined on a descriptive ground. They allow an
      optimal interpretation of the clinical aspect without, however, reaching the
      sensitivity and specificity of the microscopic examination.

PMID- 9641012
TI  - [Surgery of esophageal cancer in Liege. I. A study of mortality and perioperative
      morbidity].
AB  - BACKGROUND: To assess surgical outcome after oesophagectomy, we reviewed
      operative techniques and postoperative course among 90 patients who underwent
      oesophageal resection for malignancies from January 1989 to December 1995.
      METHODS: There were 73 males and 17 females; mean age was 64.2 years. Indications
      were squamous cell carcinoma in 49 patients and adenocarcinoma in 41.
      Preoperatively 7 patients had chemotherapy and 18 benefited from
      radiochemotherapy. There were 56 total thoracic oesophagectomies, with
      anastomosis in the neck in 34 patients and at the thoracic inlet in 22. In 34
      cases operation was limited to distal oesophageal resections. Digestive
      continuity was restored with the stomach in 62 patients, with the colon in 24,
      and with a jejunal loop in 4. A feeding jejunostomy was constructed in 48
      patients with a gastric transplant. RESULTS: Mortality was 10% (9 patients),
      decreasing from 18.5% (before 1993) to 3.8% (since 1993). One patient died in the
      colonic graft group and 8 in the gastric pull-up group. Postoperative
      complications occurred in 9 patients after colonic interposition and in 23 after
      gastric pull-up; they consisted in pulmonary infection or insufficiency in 26
      patients, cerebrovascular accident in one, renal insufficiency in 2, recurrent
      nerve palsy in 4, and anastomotic leakage in 6. Transhiatal approach was not
      associated with a decreased incidence of postoperative deaths or complications.
      Eighteen patients (72%) developed postoperative pulmonary complications after
      preoperative chemotherapy. CONCLUSION: Oesophagectomy can be performed with low
      mortality. A colonic graft is not associated with an increased incidence of
      perioperative deaths or complications and is the substitute of choice when there
      is any question regarding gastric vascularization, or in young patients with long
      life expectancy. Preoperative neoadjuvant treatment significantly increases
      postoperative pulmonary complications.

PMID- 9641013
TI  - [Dysfunction of the sphincter of Oddi in cholecystectomy patients].
AB  - Sphincter of Oddi dysfunction (SOD) is an obstructive syndrome of the papilla not
      resulting from a stone. It may cause recurrent biliary type pain to
      cholecystectomized patients. SOD is caused by sphincter dyskinesia or benign
      stenosis. Diagnosis is usually based on symptoms, serum biochemistry, endoscopic
      retrograde cholangiopancreatography and Sphincter of Oddi manometry. The latter
      is the best means of evaluating Sphincter of Oddi dynamics. However, because of
      the many inconveniences of Sphincter of Oddi manometry and of its high morbidity
      rate, it is seldom used. Non invasive techniques, such as cholescintigraphy, have
      been developed to replace Sphincter of Oddi manometry in diagnosing SOD. Patients
      can be cured by sphincterotomy. Certain drugs could also be effective but few
      controlled studies have been carried out of date.

PMID- 9641014
TI  - [Long QT syndrome: from clinical discovery to molecular etiopathogenesis].
AB  - Before the era of Molecular Biology the etiopathogenic mechanism of the long QT
      Syndrome (LQTS) was hypothetized to be an inhomogeneity in the innervation of the
      myocardium by the sympathetic system resulting in abnormal myocardial
      repolarisation, prolongation of the QT interval and various rhythm disorders. The
      progress of Molecular Biology has led to abandon this hypothesis; it is now
      agreed that the etiopathology of the various forms of the LQTS and of the
      arrythmias which are associated with it lies in the presence of mutations
      localized on genes coding either for cardio-specific ionic channels or for
      proteins which modulate the activity of these ionic channels. Thus, the
      alterations, direct or indirect, of these cardio-specific ionic channels lead to
      a delayed repolarization of myocardial cells which manifest itself on the
      electrocardiogram by a prolongation of the QT interval. This delayed
      repolarization of myocardial cells would induce a reactivation of myocardial
      ionic channels of the L-Ca++ type which leads to the development of secondary
      late depolarization which represent the underlying cellular mechanisms for
      "torsade de pointes". This hypothesis is experimentally reinforced by the
      observation both in animals and in men of a prolongation of the QT interval as
      well as aspecific tachyarrythmias after pharmacologic blockade of myocardial
      potassium channels. Therefore the long QT syndromes probably find their origin in
      genetic abnormalities of the electro-ionic system of the heart whereas the
      mechanical function and the autonomic innervation appear to be entirely normal.

PMID- 9641015
TI  - [Transdermal replacement hormone therapy: a trend or an advantage?].
AB  - This review describes the clinical usefulness of transdermal hormone replacement
      therapy. This route of administration is particularly important in women with
      hypertriglyceridemia, in hypertensive postmenopausal women, in women who smoke or
      have an increased risk of biliary or liver disorder, for those who display a
      reduced glucose tolerance or in women who are at risk of thrombotic disorders.
      The avoidance of the "first passage effect" is ensured by the transdermal
      application of estrogen and probably explains the superiority of this route of
      steroid administration.

PMID- 9641016
TI  - [Cancer of the breast: mass screening by mammography is not justified].
AB  - Mass mammographic screening for breast cancer is, for some, obviously beneficial.
      For others, it is not justified in countries like ours and could even entail
      deleterious consequences. This "controversy" exposes the views and justifications
      pro and contra.

PMID- 9641017
TI  - [Mass screening of breast cancer: response and justification].

PMID- 9641018
TI  - [Medico-legal aspects of occupational deafness. Update 1998].
AB  - The author gives new information on medicolegal sight of professional deafness in
      relation to his paper published in this review in 1995.

PMID- 9641019
TI  - [How I study the assessment of the risk of sudden death in Wolff-Parkinson-White
      syndrome].
AB  - The identification of a WPW impose to evaluate the potential risk of sudden
      cardiac death. The risk depends on the duration of the refractory period of the
      accessory pathway. If the preexcitation disappears when the patient is stressed
      on a treadmill, there is no risk of sudden death. If it does not, an
      electrophysiological study will have to be performed to measure the refractory
      period of the accessory pathway. If a risk of sudden death is present (refractory
      period < 220 ms), the accessory pathway has to be ablated using radiofrequency.

PMID- 9641020
TI  - [Drug clinics. The drug of the month. Alendronate (Fosamax)].
AB  - Alendronate (Fosamax, Merck Sharp & Dohme) is an aminobisphosphonate which
      inhibits bone turnover by suppressing the activity of osteoclasts without
      increasing the risk of osteomalacia. Alendronate is highly effective at
      preventing bone loss associated to absence of endogenous estrogen and induces a
      sustained increase in bone mass. Fosamax is indicated and reimbursed in the
      treatment of osteoporosis in postmenopausal women, with either an history of bone
      fracture confirmed by X-ray exam or obvious osteoporosis assessed by bone mineral
      density measurement. The recommended dosage is 10 mg once daily, continuously.
      The drug should be absorbed after an overnight fast to improve its
      bioavailability and with a big glass of plain water to reduce the risk of
      oesophageal ulcerations. Large randomized controlled trials for up to 3 years
      have demonstrated that alendronate is able to reduce the risk and rate of
      occurrence of vertebral and nonvertebral fractures in postmenopausal women.

PMID- 9641021
TI  - [Info-congress. Bisoprolol in congestive heart failure].

PMID- 9641022
TI  - [Prevention of breast cancer using tamoxifen].

PMID- 9641023
TI  - Biliary microliths--a lot of sound for small stones.

PMID- 9641024
TI  - Veno occlusive disease.

PMID- 9641025
TI  - Complications of acute pancreatitis.

PMID- 9641026
TI  - Biliary microlithiasis.

PMID- 9641027
TI  - Helicobacter pylori in dyspeptic Jordanian patients.
AB  - To study the prevalence of Helicobacter pylori infection in dyspeptic Jordanian
      patients. PATIENTS AND METHODS: Two hundred and twenty seven consecutive
      dyspeptic Jordanian patients were studied with endoscopy, endoscopic biopsies,
      culture, and CLO urease testing for the detection of H. pylori. RESULTS:
      Helicobacter pylori positivity in both culture and CLO urease testing was 86%,
      being 78% in culture and 80% in CLO test separately. The majority of our patients
      were in the age range 21-60 years and H. pylori positivity was more than 90% in
      them. CONCLUSION: Helicobacter pylori is a common infection in dyspeptic
      Jordanian patients regardless of the underlying cause. Males were affected more
      than females.

PMID- 9641028
TI  - Helicobacter pylori infection in patients with perforated duodenal ulcer.
AB  - AIM: Perforation is the commonest complication of duodenal ulcer. Helicobacter
      pylori is found in 95% patients with duodenal ulcer. However, there is paucity of
      reports on prevalence of H. pylori infection in patients with duodenal ulcer
      perforation. We, therefore compared the incidence of H. pylori infection in
      patients with duodenal ulcer perforation with the incidence in patients having
      complicated duodenal ulcers and non-ulcer dyspepsia. PATIENTS AND METHODS: The
      study was conducted on 45 patients (complicated duodenal ulcer 15, duodenal ulcer
      perforation 15, non-ulcer dyspepsia 15). Per-operative punch antral biopsies were
      taken in patients with duodenal ulcer perforation whereas endoscopic punch
      biopsies of antrum were taken in patients with non-ulcer dyspepsia. The criteria
      for H. pylori positivity was i) growth of H. pylori on culture, ii) combination
      of rapid urease test (RUT) and Giemsa staining, combination of RUT and Gram stain
      being positive for H. pylori. RESULTS: While 9 of 15 cases with complicated
      duodenal ulcer, 7 of 15 cases with non-ulcer dyspepsia were positive for H.
      pylori, none of the patients with duodenal ulcer perforation tested positive for
      H. pylori (p < 0.000). All patients with perforated duodenal ulcer had
      histological gastritis (H. pylori -ve). Fourteen of 15 patients (9 H. pylori +ve,
      5 H. pylori -ve) with complicated duodenal ulcer and 9 of 15 patients (7 H.
      pylori +ve) with non-ulcer dyspepsia had histological gastritis. CONCLUSION:
      Patients with duodenal ulcer perforation do not have H. pylori infection. H.
      pylori negative patients of duodenal ulcer may have more predilection for
      perforation.

PMID- 9641029
TI  - Is vegetarianism a precipitating factor for gallstones in cirrhotics?
AB  - AIM: To study the association of factors such as alcohol, smoking and
      vegetarianism with presence of gallstones amongst cirrhotics. PATIENTS AND
      METHODS: Data on alcoholism, smoking and vegetarianism was collected from the
      case records of 669 cirrhotics with (76) or without gallstones (593)
      retrospectively. Relative risk for the factors was computed individually and in
      combination controlling for the effects of alcoholism and smoking on
      vegetarianism. RESULTS: Alcoholism and smoking were of low relative risk [R.R
      1.27 (95% CI 0.82 to 1.96), and 1.02 (95% CI 0.65 to 1.61) respectively] while
      vegetarianism was associated with high risk for gallstone formation in cirrhotics
      [R.R 2.74 (95% CI 1.65-4.53)]. Vegetarian men had a relative risk of 3.02 (95% CI
      1.75-5.22) irrespective of their alcoholic status. If women were alcoholic the
      relative risk increased to 7.03 (95% CI 3.26-15.12). Controlling for effects of
      gender and alcoholism, vegetarian cirrhotics had a 3 times greater risk for
      gallstone formation [Mantel Haenszel Relative Risk 3.18 (95% CI MHRR 1.82-5.56)].
      CONCLUSIONS: Cirrhotic, vegetarian women in South India have a much higher risk
      for gallstones, if they are alcoholic. Alcoholic men who are vegetarians are at a
      greater risk for gallstone disease.

PMID- 9641030
TI  - Malignant jejunal polyp in Peutz-Jeghers syndrome.

PMID- 9641031
TI  - When a hepatologist develops hepatitis!

PMID- 9641032
TI  - Adjuvant preoperative radiotherapy for resectable rectal cancer. Do we have an
      answer now?

PMID- 9641033
TI  - Management of foreign bodies of the upper gastrointestinal tract.
AB  - The use of flexible endoscopes had made removal of foreign bodies in the upper
      gastrointestinal tract easier and safer. We describe our experience of 49 cases
      of foreign bodies of the upper gastrointestinal tract. Majority (67%) of the
      patients were children and only 4 patients (8%) were above 45 years of age. The
      most common foreign bodies encountered were coins (25), fruit stones (4) and
      dentures (3). In 29 patients foreign bodies were lodged in the oesophagus and in
      15 cases in the stomach. Forty one patients were considered for endoscopic
      removal of the foreign bodies and 40 could be managed successfully. There were no
      procedure related complications. We conclude that endoscopic removal of the
      foreign bodies of the upper gastrointestinal tract is a safe and effective
      technique.

PMID- 9641034
TI  - Hepatitis B and hepatitis C in multitransfused children.
AB  - The study was conducted on 75 multitransfused children aged between 2 and 13
      years who attended the Department of Paediatrics, LNJPN Hospital, New Delhi from
      July 1990 to July 1991. These included 64 cases of thalassaemia major, 4 cases of
      haemophilia, 3 patients of acute lymphatic leukaemia and one each of acute
      myeloid leukaemia, aplastic anemia, chronic idiopathic thrombocytopenic purpura
      and acute haemorrhagic pancreatitis. HBsAg was tested in all, Anti-HBc was tested
      in 44 patients and Anti-HCV in 43 patients. Anti HDV was tested in HBsAg positive
      patients and IgM anti-HAV was tested in patients suffering from hepatitis. Liver
      function tests were evaluated in all patients. HBsAg was positive in 31% of
      patients; 40% of males and 15% of females were HBsAg positive, the difference
      being statistically significant. 84% of patients were Anti-HBc positive, 21% were
      anti HCV positive, 4% were Anti HDV positive. 15% of the patients had post
      transfusion hepatitis. Anti HCV was present in 57% of the hepatitis patients;
      none had anti-HAV IgM.

PMID- 9641035
TI  - Malignant gastroparesis and outlet obstruction in carcinoma gall bladder.
AB  - INTRODUCTION: Malignant gastroparesis and mechanical gastric outlet obstruction
      are two major accompaniments of advanced upper abdominal malignancies. The
      incidence of such problems has not been well documented in patients of carcinoma
      gall bladder. The aim of this study was to determine the incidence of gastric
      outlet problems in patients of carcinoma gall bladder and correlate them with
      clinical presentation. The role of prophylactic gastrojejunostomy (GJ) and its
      postoperative outcome was also evaluated. PATIENTS AND METHODS: Thirty seven
      patients of carcinoma gall bladder were prospectively studied. Twenty five
      patients underwent radio labelled solid meal gastric emptying study and eleven of
      these underwent prophylactic GJ and followup gastric emptying study in early
      postoperative period. RESULTS: Mechanical gastric outlet obstruction was seen in
      10 (27%) patients. Delayed gastric emptying on scintigraphic study was found in
      10 (40%) of remaining patients (n = 25). Only 6 (60%) of these patients were
      actually symptomatic. All patients who had delayed gastric emptying also had an
      advanced disease. No correlation was found between delayed gastric emptying and
      presence of jaundice and/or serum levels of bilirubin. Prophylactic GJ had 18%
      postoperative morbidity as compared to 28.5% for therapeutic GJ done during the
      same period. Oral feed were started latest by 11th postoperative day.
      Prophylactic GJ did not affect gastric emptying patterns in early postoperative
      period. CONCLUSION: Mechanical gastric outlet obstruction was present in 27%
      patients. Delayed gastric emptying was seen in 40% of remaining patients with
      carcinoma gall bladder. Delayed gastric emptying correlated well with symptoms of
      gastric stasis and the stage of disease. Functioning of gastrojejunostomy was not
      fully dependent on presence or absence of malignant gastroparesis.

PMID- 9641036
TI  - [Treatment of alcohol abuse].

PMID- 9641037
TI  - [Epidemiology of hepatitis C].

PMID- 9641038
TI  - [Hereditary long QT syndrome].
AB  - The Long QT Syndrome (LQTS) is a hereditary disease, characterized by a prolonged
      QT-interval on the electrocardiogram and a high risk of syncope and sudden death
      due to ventricular arrhythmias. LQTS must be suspected in apparently healthy
      children and young people with syncope after emotional or physical stress.
      Untreated symptomatic patients have a high mortality, which is markedly reduced
      by sympathetic block. The knowledge of the diagnostic criteria for the LQTS, a
      detailed history including a family history and an ECG-recording with measurement
      of the QT-interval in every patient with inexplicable syncope will advance the
      diagnosis of the LQTS and improve the survival of these patients after proper
      therapy. The current knowledge on the molecular genetics, epidemiology,
      mechanisms of arrhythmias and therapy are presented with special emphasis on the
      defects in the control of ionic transport over the cell membrane caused by
      mutations in ion channels.

PMID- 9641039
TI  - [Lung physiotherapy as prophylaxis against atelectasis and pneumonia after
      abdominal surgery].
AB  - Postoperative pulmonary complications play a significant role for the
      postoperative morbidity after abdominal surgery. To prevent this, an array of
      methods, such as lung physiotherapy, incentive spirometry, or mask treatment with
      positive airway pressure are used. The available controlled studies indicate that
      none of these treatment modalities reduce the occurrence of postoperative
      atelectasis, but only lung physiotherapy is able to reduce the development of
      postoperative pneumonia. Thus, we recommend lung physiotherapy as prophylactic
      treatment after abdominal surgery. The value of optimized pain alleviation and
      mobilisation in addition to lung physiotherapy should be evaluated in future
      trials.

PMID- 9641040
TI  - [Antabus treatment in general practice. A pharmaco-epidemiological study of
      prescription patterns based on a prescription database].
AB  - Denmark has a long tradition for the use of alcohol-aversive drugs in the
      treatment of alcoholism, most commonly disulfiram (Antabuse). The purpose of this
      study was to examine the prescription patterns for disulfiram in Danish general
      practice on an individual level. By means of a prescription database we analysed
      150,787 prescriptions on reimbursed medicine to persons who had redeemed
      prescriptions for alcohol-aversive drugs during the period 1.1.1993 to 31.12.1995
      in the County of Funen. Prevalence of disulfiram treatment was 12 per 10,000
      inhabitants, three-year prevalence 75 per 10,000 inhabitants and incidence 21 per
      10,000 inhabitants per year. Eighty-seven percent of treatments were stopped at
      (or before) the expiration of one prescription, and relapse was frequent (46%).

PMID- 9641041
TI  - [Detoxication in hospital contra detoxication in detention].
AB  - In the present study, 61 persons taken into police custody due to drunkenness
      were compared with 57 persons admitted to hospital due to intoxication with
      alcohol. The persons with alcohol problems taken into police custody numbered
      more younger men, fewer retired persons and the alcohol problems were more often
      acute intoxication than alcohol dependence. None of the persons placed in police
      custody were advised to seek help for their alcohol problems in contrast to 45
      out of the 57 admitted to the hospital who started treatment. Detoxification in
      hospitals is far more suitable to motivate persons with alcohol problems to seek
      help. Detoxification should, for non criminal intoxicated people, be performed in
      hospitals.

PMID- 9641042
TI  - [Factors related to suicidal behavior among alcoholics].
AB  - Of 181 alcoholics who consecutively sought treatment as out- or inpatients, 68
      (37.6%) had attempted suicide at least once. Compared with non-attempters, the
      suicide attempters were significantly more likely to be female, have had a
      chaotic upbringing and to have known suicide attempts in the family and social
      circle. Significantly more attempters suffered from depressive disorder, feelings
      of hopelessness, anxiety attacks, agoraphobia, substance abuse or cluster B
      personality disorders (dissocial, impulsive, borderline, and histrionic). Also
      significantly more suicide attempters had committed crimes and received early
      pension. Assessment of coping showed that suicide attempters had a significantly
      lower tendency to make plans or to make the best of a stressful situation by
      growing from it. They were significantly more likely to show mental
      disengagement, to resort to denial and drink alcohol or take drugs when faced
      with stressful events or difficulties. When evaluated on the Addiction Severity
      Index Scale, the suicide attempters were found to have a significantly greater
      need of treatment.

PMID- 9641043
TI  - [Computer assisted neuropsychological testing of children].
AB  - The purpose of the study was to examine the feasibility of a computer-assisted
      neuro-psychological test program, the Neurobehavioral Evaluation System (NES), in
      six to seven year-old children. We administered three NES tests, Finger Tapping
      (FT), Continuous Performance Test (CPT) and Hand-Eye Coordination (HEC) to
      Faroese and Danish children. The FT and CPT were of appropriate difficulty, while
      the HE was too difficult for the majority of the children. Boys obtained better
      scores than the girls, and children who were familiar with computers and video
      games performed better than those without such experience. Older children also
      obtained better scores than younger ones, especially in the Faroese group. The
      Danish children performed better than the Faroese in FT and CPT. In HE there was
      no difference. The NES tests are feasible for children at this age, but
      appropriate comparison groups must be secured.

PMID- 9641044
TI  - [Mortality and worsening of prognosis for patients with aortic stenosis while on
      the waiting list].
AB  - In a prospective study, 99 consecutive patients with an operative indication due
      to severe aortic stenosis (AS) were put on a surgical waiting list. The waiting
      time to aortic valve replacement (AVR) averaged 6.3 months (0.5-19 months). There
      were 58 men and 41 women with a mean age of 61 years (21-82 years). The patients
      were divided into three groups: group 1 (N = 81) with an uneventful stay on the
      waiting list; group 2 (N = 11) with significant worsening of a prognostic index;
      and group 3 (N = 7) with patients who died during the waiting time. The waiting
      list death rate was 13.5%/patient-year compared with a post-AVR death rate of
      4.9% patient-year (p < 0.05) with a mean post-AVR follow-up of 5.7 years.
      According to a prognostic index (Cox regression model) at inclusion, group 2
      patients had a predicted 7-year post-AVR survival probability of 72%, but only of
      61% according to their prognostic index immediately preoperatively; their
      observed 7-year post-AVR survival was 60%. Logistic regression analysis
      identified high age, short duration of symptoms, signs of severe hypertrophy and
      strain in the ECG, female gender, and deranged left ventricular diastolic
      function (related to severely increased left ventricular muscle mass) as
      independent predictors of prognostic worsening and death while on the waiting
      list. The predictive models did not allow sufficiently accurate identification of
      the patients at risk during the waiting period. The consequences of a surgical
      waiting period averaging 6 months are serious for AS patients. The death rate is
      high and a subgroup worsens its prognostic profile with a significantly reduced
      post-AVR long-term survival as the result.

PMID- 9641045
TI  - [Segond fracture in acute knee injuries].
AB  - Two patients with a lateral tibia avulsion fracture (Segond fracture) are
      presented. The correlation between the Segond racture and rupture of the anterior
      cruciate ligament is pointed out, as well as the fact that patients with Segond
      fracture and rupture of the anterior cruciate ligament often have other injuries
      such as meniscus lesions and lesion of the medial collateral ligament.

PMID- 9641046
TI  - [Combined nitroglycerin-heparin infusion in mesenteric venous thrombosis].
AB  - Surgical treatment of venous mesenterial thrombosis (VMT) may result in a short
      bowel-syndrome. We report the successful outcome of combined intravenous heparin
      and nitroglycerine in a case of VMT followed by a limited resection of small
      bowel.

PMID- 9641047
TI  - [Screening for colorectal cancer--diminishing number of emergency admissions?].

PMID- 9641048
TI  - [Meta-analyses to reveal insufficient mega-trials].

PMID- 9641049
TI  - [Contribution to anticholesteremic agents?].

PMID- 9641050
TI  - [Reteplase. A new thrombolytic agent in the treatment of acute myocardial
      infarction].

PMID- 9641051
TI  - [Authorship of scientific articles].

PMID- 9641052
TI  - [Endogenous retroviruses in the human genome].

PMID- 9641053
TI  - [Reliability of the epidural test dose].
AB  - Complications associated with epidural anaesthesia include accidental
      intravascular or subarachnoid epidural catheter misplacement resulting in
      systemic toxicity and total spinal block, respectively. Epidural test doses are
      used routinely to prevent these events. It is not known whether the use of test
      doses improves the safety of epidural anaesthesia. The reliability of the
      epinephrine test dose in terms of detecting intravascular injection is impaired
      in elderly patients, patients receiving beta-blockers, patients undergoing
      vascular surgery, patients under general anaesthesia, and in women in labour. The
      ability of the epidural test dose to detect subarachnoid injection remains
      unknown. Studies are needed to determine 1) the reliability of the epidural test
      dose among different groups of patients, 2) the safety of the test dose, and 3)
      the incidence of epidural catheter misplacements.

PMID- 9641054
TI  - [Shoulder instability].
AB  - The importance of the labrum and glenohumeral ligament complex for the stability
      of the shoulder joint has been known since the beginning of this century.
      Shoulder instability may be classified into two large groups. TUBS, characterized
      by Traumatic, Unidirectional instability and Bankart lesion which often requires
      Surgery. The second group AMBRI, is characterized by Atraumatic,
      Multidirectional, Bilateral instability that often responds to Rehabilitation,
      but in case of surgery Inferior capsular shift is indicated. The high recurrence
      rate after primary traumatic anterior dislocation in young adults has caused an
      ongoing discussion about the indications for primary surgery. Anatomical
      reconstruction focusing on the pathoanatomy is recommended due to better results
      and a lower complication rate as compared to non-anatomical reconstruction that
      alters the normal anatomy and kinematics. The recurrence rate after arthroscopic
      Bankart repair is still generally higher than after open surgery but may be
      improved by better patient selection.

PMID- 9641055
TI  - [Balloon dilatation of congenital aortic stenosis].
AB  - We evaluated the catheterization results and follow-up echocardiographic data in
      all (n = 31) patients undergoing balloon dilatation for congenital aortic valve
      stenosis at Skejby University Hospital from May 1987 to October 1996. Patients
      were between three weeks and 35 years of age (median 12.1 years). Peak-to-peak
      systolic pressure gradient was reduced by 59%, from 74 +/- 17 to 30 +/- 20 mmHg
      (p < 0.0001). Balloon valvuloplasty was successful in 26 (84%) patients. At
      follow-up 38 +/- 33 months after balloon valvuloplasty, 19 of these 26 patients
      (73%) had a persistent reduction in gradient compared with that before
      valvuloplasty. In the seven patients who had been operated during the follow-up
      period, balloon valvuloplasty had delayed surgical intervention by 6-97 (median
      38) months. Balloon valvuloplasty is an effective, low risk palliative procedure
      in patients with congenital aortic valve stenosis.

PMID- 9641056
TI  - [The frequency of secondary cataract after extracapsular cataract extraction].
AB  - A complication of extracapsular cataract extraction is posterior capsule
      opacification (secondary cataract). In this study we found that 26.0% of patients
      operated for cataract with extracapsular technique were treated for secondary
      cataract. The average postoperative time to treatment with Nd-YAG
      lasercapsulotomy was 15.2 months with a follow-up time of 34 months.

PMID- 9641057
TI  - [Brain damage in relation to occurrence of retinopathy of prematurity. A regional
      ophthalmologic follow up of premature infants born 1982-1984].
AB  - Regular ophthalmic surveillance started in 1982 for all surviving prematures in
      Frederiksborg County considered at risk of developing retinopathy of prematurity
      (ROP). During 1982-1984 185 infants of gestational age 25-35 weeks at delivery
      were examined; blindness eventually appeared in four out of the 28 who showed
      some stage of ROP. All 28 attended ophthalmic reassessment at age 7-10 years and
      were compared with 60 of the same cohort without evidence of ROP. At follow-up (n
      = 88) there was evidence of psychomotor disturbances in 45 children, manifesting
      as major CNS damage in 21, and minor in 24. With correction for drop-outs the
      regional frequency of severe CNS damage (mainly cerebral palsy and mental
      retardation) was 29.6% for gestational ages < 32 weeks at delivery and 24% as
      calculated for birth weights < 1500 g. An analysis of perinatal factors based
      mainly on matched pairs did not indicate any definite association with subsequent
      damage to eye or brain, and statistically there was no association between
      severity of ROP and CNS impairment. We have no explanation for the high frequency
      of CNS impairment at follow-up.

PMID- 9641058
TI  - [Cryotherapy of retinal prematurity in Denmark 1992-1996].
AB  - Retinopathy of prematurity (ROP) is a vasoproliferative disorder often met in
      infants of very preterm delivery. Lower stages usually regress spontaneously, but
      progression to so-called threshold-ROP should lead to anterior retinal ablation
      therapy, by cryopencil or laser. Fifty-three Danish infants born 1992-96 were
      evaluated in the University eye clinic of Rigshospitalet for the disease; 65 eyes
      of 36 infants had cryotherapy; eight infants developed severe bilateral visual
      handicap (22%). The reason for not giving cryotherapy to the remaining 17 was:
      too late referral in five, and ROP below threshold in 12; seven of the 17 later
      appeared in the (mandatory) national register for childhood visual handicap.
      Perusing these data the other way round, 15 of the registered 18 cases were thus
      known to us, while three had escaped referral. With reservation for the small
      numbers included, the national trend at present is an increasing annual number of
      subjects receiving retinal ablation therapy for ROP, and a decrease in severe
      visual impairment due to the disorder. Obviously all preterm infants at risk
      should be under early regular ophthalmic surveillance for ROP.

PMID- 9641059
TI  - [Conjunctival nevi in Denmark 1960-1980. A 21-year follow-up].
AB  - The clinicopathological characteristics of 343 naevi of the conjunctiva were
      studied. A significant increase in the number of naevi excised per year was
      observed. This may have been caused by an increased exposure to actinic rays. An
      approximately even distribution was found between the three main locations:
      caruncle, limbal area and eye ball. Intrastromal naevi were excised at a higher
      median age than compound naevi, and the lowest median age at excision was for
      junction naevi, which is in accordance with the known histopathological nature of
      naevi. Recurrence occurred in nine patients (2.7%), and one had transformed into
      a malignant melanoma. Eight of the recurring naevi were located in the limbal
      area. Eight of the nine patients were women, suggesting hormonal factors as a
      possible cause. Recommendations for the handling of conjunctival naevi are given,
      based on the present findings and on previous reports.

PMID- 9641060
TI  - [Significance of idiopathic preterm birth in relation to previous and future
      pregnancies].
AB  - This registry-based cohort study aimed to describe the relationship between
      pregnancy complications in the first and second pregnancy, focussing on
      idiopathic and indicated preterm birth of singleton infants in either pregnancy.
      The cohort consisted of all women living in Denmark with a first singleton birth
      in 1982 and a second in the period 1982-1987 (13,967 women). The risk of a second
      preterm birth was not significantly different between women who had an idiopathic
      or an indicated first preterm birth (15.2 and 12.8% respectively). Adjustment by
      logistic regression analysis for other risk factors for preterm birth did not
      influence the relative risk (6.0 before 32 weeks and 4.8 between 32 and 36 weeks)
      of a second preterm birth subsequent to a first one. Women with idiopathic
      preterm delivery in their first or second pregnancies give birth to infants with
      lower birth weight in previous or subsequent pregnancies. Emergency cesarean
      section in a first term pregnancy was a risk factor for subsequent idiopathic
      preterm birth.

PMID- 9641061
TI  - [Increased concentration of Na,K-pumps in skeletal muscles of patients with
      chronic obstructive lung disease. Significance of magnesium depletion and
      treatment with glucocorticoids].
AB  - Patients with COLD may develop Mg depletion due to inadequate nutrition or
      treatment with diuretics and beta 2-agonists. In 36 consecutive COLD patients
      skeletal muscle concentrations of Mg and K were reduced by 22% and 14%,
      respectively, compared to 23 age- and sex-matched controls (p < 0.001). Patients
      receiving diuretics showed a further reduction of muscle Mg (-31%) and K (-27%)
      compared to controls. The mean concentration of Na,K pumps was increased by 31%
      (p < 0.001), while a more pronounced increase (+61%) was seen in 12 intensive
      care patients receiving high dosages of glucocorticoids. Thus muscle
      concentrations of Mg and K are reduced in COLD patients and are associated with
      an upregulation of the Na,K-pump concentration. It is plausible that this
      upregulation may be caused by glucocorticoid treatment. The clinical benefits of
      glucocorticoids may therefore in part be due to an increased activity and
      capacity of the Na,K-pump and thereby in a possible enhancement of muscle force.

PMID- 9641062
TI  - [Amyl nitrite poisoning].
AB  - Two cases of amylnitrite poisoning are presented. In both cases, severe
      methaemoglobinemia developed after ingestion of approximately 10 ml of
      amylnitrite. When admitted to hospital, both patients were deeply cyanosed, and
      arterial blood samples were noticed to be chocolate brown. They were
      intravenously treated with methylene blue. Within one hour the condition of both
      patients had improved dramatically, and blood gas-samples had normalised. In
      cases of cyanosis with no obvious genesis, poisoning with amylnitrite should be
      considered.

PMID- 9641063
TI  - [Acute bacterial meningitis--NOSce te ipsum (know yourself)].

PMID- 9641064
TI  - [Increased blood pressure should be efficiently treated. Results from the
      Hypertension Optimal Treatment Study (the HOT-study)].

PMID- 9641065
TI  - [Fibromyalgia].

PMID- 9641066
TI  - [Develpment of asthma prevalence 1986-1992].

PMID- 9641067
TI  - [More about ticks].

PMID- 9641068
TI  - [More about ticks].

PMID- 9641069
TI  - [More about ticks].

PMID- 9641070
TI  - The Management of Intractable Pain Act: what will it mean for physicians and
      patients in West Virginia?

PMID- 9641071
TI  - Malaria in West Virginia: forty cases seen at West Virginia University Hospital.
AB  - In the U.S., malaria predominately occurs in travelers and immigrants. We report
      a series of 40 cases at West Virginia University Hospital, and 24 of whom were
      students who had visited areas of East Africa, West Africa and Asia usually in
      either December, January, August or September. Most patients (79%) reported a
      previous episode of malaria, and P. falciparum was identified in 60%. Fever,
      chills and rigors were the most common symptoms. Correct use of malaria
      prophylaxis was recorded in five patients, and only two of these were students.
      Successful outcomes were recorded in all but one patient. Our series suggests
      that international students would benefit from the proper use of
      chemoprophylaxis, thus decreasing the number of cases of malaria seen in
      university settings.

PMID- 9641072
TI  - A case report of idiopathic pulmonary ossification.
AB  - Idiopathic pulmonary ossification is a rare disease. Most commonly, it affects
      middle-aged men. Its etiology is unknown. We present a case of nodular type
      idiopathic pulmonary ossification in a 42-year-old, white male who had one
      episode of hemoptysis.

PMID- 9641074
TI  - The organization of children's same-sex peer relationships.

PMID- 9641073
TI  - Utilization of diagnostic resources for meningoencephalitis in the pediatric ICU.
AB  - To determine whether a Pediatric Critical Care team has an evolution of medical
      practice that decreases the utilization of diagnostic tests and consults, we
      examined the records of 69 patients admitted for meningitis or
      meningoencephalitis at Women and Children's Hospital in Charleston, W.Va., a
      university-affiliated, teaching hospital. The study was conducted from August
      1990 to August 1994. We found that utilization of diagnostic resources (UDR)
      decreased over the four years, and there was a direct relationship between an
      increase in severity of illness and an increase in UDR. When adjusted per
      severity of illness, UDR decreased by $423 per year. The presence of a consult
      was a factor leading to an increase in resources, which were associated with an
      increased utilization of diagnostic tests and length of stay. The consultation
      rate was independent of the severity of illness and experienced a decrease over
      the years.

PMID- 9641075
TI  - The popularity of friendship and the neglect of social networks: toward a new
      balance.

PMID- 9641076
TI  - Children's development within peer groups: using composite social maps to
      identify peer networks and to study their influences.

PMID- 9641077
TI  - The peer ecology of popularity: the network embeddedness of a child's friend
      predicts the child's subsequent popularity.

PMID- 9641078
TI  - Cardiovascular applications of lasers: searching for a niche.

PMID- 9641079
TI  - Transmyocardial laser revascularization: historical background and future
      directions.
AB  - Transmyocardial laser revascularization (TMLR) was investigated as a possible
      treatment alternative for patients with refractory coronary artery disease. This
      paper is a summary of nearly four decades of research by the authors. Beginning
      in 1969 experimental studies were conducted on the beating heart. A prototype 450
      W carbon dioxide laser was used to create channels in the ischemic myocardium.
      Initial clinical studies began in 1984. A protocol was developed for TMLR as an
      adjunct to CABG in those patient who had at least one vessel which could be
      bypassed and areas of ischemia which were not amenable to bypass. In the early
      1990's the development of a 850 W CO2 laser for clinical use allowed us to begin
      investigation of TMLR on the beating heart. Patients with end stage coronary
      artery disease who were not candidates for other forms of treatment were
      selected. The early results are encouraging with patient followup of from 3
      months to 5 years. There are numerous controversies regarding the effects of TMLR
      on myocardial function and perfusion. To quantify these effects the authors have
      performed acute and chronic studies on swine using sophisticated techniques with
      3D cine magnetic resonance imaging. We concluded TMLR improved left ventricular
      function and perfusion in acute and chronic ischemia.

PMID- 9641080
TI  - The physics of transmyocardial laser revascularization.
AB  - Lasers create channels through the myocardium by ablating the tissue and tissue
      ablation is achieved by breaking the molecular bonds of the organic constituents
      of the myocardium. Lasers provide the energy required to dissociate these
      molecular bonds by the interaction of laser photons with the tissue. However, the
      energy supplied to the electrons within the bonds must match specific allowed
      energy levels. Such energy matching is accomplished through different mechanisms
      by different laser wavelengths. Infrared laser photons are strongly absorbed by
      water in the tissue and it is the subsequent vaporization of the water that
      provides the energy necessary to break the bonds. In contrast, ultraviolet laser
      photons are not absorbed by water and have energies that can match those required
      for bond dissociation. Thus, ablation by ultraviolet lasers is achieved primarily
      by direct bond absorption of the photons. Both of these ablation mechanisms
      produce secondary effects that can cause injury to tissue surrounding the
      channels. The generation of steam or the gaseous breakdown products of tissue
      proteins can cause thermal injury in addition to the mechanical injury produced
      by escape of these gases into the tissue. Furthermore, shock waves generated by
      ablation are also a possible source of mechanical injury, while free radical
      molecules capable of cell injury are known to be formed after breaking chemical
      bonds. The variety of tissue interactions provided by the different lasers should
      enable the optimal laser treatment to be applied once the optimal channel
      configuration has been determined.

PMID- 9641081
TI  - Detection and assessment of laser-mediated injury in transmyocardial
      revascularization.
AB  - When channels are made through the myocardium with a laser, tissue surrounding
      the channels is injured. Thus, methods of examining and quantifying the
      histologic changes caused by laser-mediated injury are required both for
      comparison of different channel making protocols and also to help understand the
      mechanisms of transmyocardial revascularization. The two principal components of
      the myocardium, collagen and muscle, are both normally birefringent. This optical
      property can be exploited with the use of polarized light microscopy to assess
      tissue structure at the cellular and subcellular levels allowing several
      different types of injury to be detected. Increases in tissue temperature above
      60 degrees C for muscle and 70 degrees C for collagen decrease their
      birefringence and, hence, result in decreased brightness when viewed with
      polarized light. Lower temperatures may cause cell membrane injury, calcium
      overload, and the formation of contraction bands, which appear as areas of
      increased birefringence. In this way, the extent of thermal injury can be
      assessed. The same optical properties can be used to measure cell and fiber
      orientation and, hence, enable assessment of mechanical disruption of the tissue
      after ablation. Long-term remodeling of the myocardium in the form of scar
      formation, increased interstitial fibrosis, and muscle disarray can also be
      quantified. The ability to measure the acute injury and the long-term structural
      consequences of that injury with the use of polarized light microscopy should
      prove vital in determining the optimal laser "dose" required and may also reveal
      information on the mechanism(s) of benefit found with transmyocardial
      revascularization.

PMID- 9641082
TI  - Angiogenesis: a possible mechanism underlying the clinical benefits of
      transmyocardial laser revascularization.
AB  - While clinical reports indicate that significant relief of angina is achieved
      with transmyocardial laser revascularization (TMLR), the mechanisms of benefit
      are still a matter of considerable controversy. Studies in our laboratory, as
      well as in the laboratories of other investigators, have challenged the classic
      hypothesis that benefits are derived from blood flow through chronically patent
      channels. While several alternatives have been proposed, our work has focused on
      investigating the possibility that TMLR stimulates vascular growth in the region
      around the TMLR channels. We have performed studies looking at histologic markers
      of vascular growth (including vessel counting and cellular proliferation assays)
      in order to test this hypothesis, the results of which are reviewed. In brief, we
      find that TMLR markedly enhances myocardial vascular growth above what is seen
      normally in ischemic myocardium. We hypothesize that the underlying mechanism
      relates to liberation of growth factors by inflammatory cells, which are
      recruited in response to the laser induced myocardial injury. Clarification of
      whether this mechanism contributes to observed clinical benefits is of
      fundamental importance, since such understanding may suggest means of enhancing
      the process.

PMID- 9641083
TI  - Myocardial angiogenesis as a possible mechanism for TMLR efficacy.
AB  - Despite advances in the treatment of ischemic heart disease, there still exists a
      significant number of individuals for whom bypass surgery or angioplasty are not
      options. Transmyocardial laser revascularization (TMLR) is a promising technology
      that has already been shown to reduce symptoms in patients with chronic ischemic
      heart disease that is not amenable to conventional therapies. Although it appears
      that TMLR can provide symptomatic relief of angina in selected patients, the
      mechanism by which TMLR is thought to work is unclear. Recently it has been
      postulated that TMLR induces an angiogenic response and, perhaps, improves local
      perfusion to ischemic myocardial territories. A brief overview of the biology of
      myocardial angiogenesis is presented.

PMID- 9641084
TI  - Clinical studies of TMR with the CO2 laser.
AB  - OBJECTIVE: This paper reviews the current status of transmyocardial laser
      revascularization by a carbon dioxide laser. SUMMARY: Since 1990 over 3000
      patients worldwide have been treated with a carbon dioxide laser. A nonrandomized
      phase II trial was completed in 1995. A randomized controlled phase III trial has
      completed enrollment, and analysis of the follow-up is pending. METHODS: In each
      trial 200 patients with endstage coronary artery disease and severe disabling
      angina that was not amenable to conventional revascularization were enrolled.
      Preoperative evaluation included confirmation of angina class and evidence of
      reversible ischemia based on myocardial perfusion scans. Repeat evaluations were
      done postoperatively at 3, 6 and 12 months. RESULTS: 80% of the patients showed a
      significant improvement in angina class status postoperatively and 30% had no
      angina at one year of follow-up. Concomitant with this there was significantly
      less ischemia noted on follow-up perfusion scans. CONCLUSIONS: Early results from
      nonrandomized and randomized controlled trials of transmyocardial laser
      revascularization by carbon dioxide laser indicate that this technique provides
      angina relief and improved perfusion in patients with end-stage coronary artery
      disease.

PMID- 9641085
TI  - Role for holmium:YAG lasers in transmyocardial laser revascularization.

PMID- 9641086
TI  - Percutaneous transmyocardial revascularization.
AB  - Transmyocardial revascularization (TMR) is a potential therapy for patients with
      severe angina pectoris and coronary anatomy deemed unsuitable for traditional
      revascularization techniques. Investigations of TMR are reviewed with emphasis on
      studies relevant to the development of a percutaneous, catheter-based
      transmyocardial revascularization procedure (PMR). The results of the preliminary
      animal studies and description of the PMR procedure are discussed. The recently
      initiated human PMR protocol is summarized and possible future investigative
      directions are outlined.

PMID- 9641087
TI  - Transmyocardial laser revascularization--a technique in evolution.
AB  - Transmyocardial laser revascularization (TMLR) is a rapidly evolving technique
      that represents the recent rediscovery of an old therapy. A growing clinical
      experience is being assimilated into clear indications and contraindications for
      and the appropriate performance of this procedure. This technique can be judged
      to improve patient quality of life and survival in appropriately selected
      patients. The therapy should still be applied cautiously, in that a full
      understanding of its indications and mechanism of action remains in a state of
      evolution.

PMID- 9641089
TI  - Laser literature watch.

PMID- 9641088
TI  - Transmyocardial laser revascularization: current experience and future direction.
AB  - Transmyocardial laser revascularization (TMR) with the CO2 laser (PLC Medical
      Systems, Inc., Franklin, MA) appears to improve the quality of life and event
      free survival of end-stage coronary artery disease patients. Application of this
      technology prior to clinical instability, along with diligent anesthetic support,
      careful patient selection, and perioperative management, are essential to a
      successful outcome. Rush-Presbyterian-St. Luke's Medical Center became the fifth
      clinical site to investigate TMR under Phase II and Phase III U.S. Food and Drug
      Administration (FDA) protocols. This clinical experience includes a total of
      seventy-nine patients, of whom sixty-three had sole TMR utilizing a minimally
      invasive approach on the beating heart. Lessons learned, to optimize patient
      selection and operative- and postoperative management, will be delineated and the
      future direction of TMR will be discussed.

PMID- 9641090
TI  - A catalogue of anomalies and traits of the permanent dentition of southern
      Chinese.
AB  - Variations in size, form and morphology of the teeth can result in anomalies such
      as macrodontia, microdontia, hyperdontia, hypodontia, double tooth, dens
      evaginatus, dens invaginatus, and talon cusp. A trait may occur more commonly in
      certain ethnic groups. Among these traits are shovel-shaped incisors, lingual
      tubercle, Carabelli's trait and protostylid of the molars. Because people are
      traveling more frequently than ever before, and there are many migrants in
      different parts of the world, it is increasingly important for dental
      professionals to be aware of the characteristics and prevalence of the anomalies
      and traits that occur in the different ethnic groups, so as to be able to make
      valid clinical judgments and to provide the appropriate treatment. The
      characteristics of these anomalies and traits are presented along with the
      prevalence figures in the southern Chinese.

PMID- 9641091
TI  - The maxillary molar mesial sub-occlusal enamel web: identification of a
      previously unreported tooth structure: the maxillary Rainey web.
AB  - This article describes the anatomical structures of the suspensory web of enamel
      in the area formerly known as the mesial "fossae," which has been assumed to be a
      single "pit" and the area immediately adjacent mesially, formerly known as the
      mesial marginal ridge "fossae." This structure lies anterior to the predominant
      feature of the occlusal table of the maxillary first molars, the oblique or
      transverse ridge, and distal to the mesial marginal ridge.

PMID- 9641092
TI  - Children's sense of pleasure from nitrous oxide therapy during dental visits.
AB  - The purpose of the present study was to measure feelings of pleasure by children
      who were undergoing dental treatment under nitrous oxide therapy during
      consecutive treatment sessions, and at a six-month follow-up visit. Fifty-two
      children between the ages of 3 and 5 years (mean age 4.3 +/- 1.06) children, who
      required two or more operative treatment visits participated in the study. At the
      conclusion of the initial treatment and after sufficient time for the effects of
      the nitrous oxide therapy to subside, patients were asked about their feelings
      from the gas. At subsequent visits, patients were asked the same questions at the
      beginning of each treatment session. The same was done at the beginning of a six
      month follow-up visit. In general, there was a decrease in pleasure among those
      who experienced three or more visits. Extraction, in addition to operative
      treatment, did not result in a decrease in the sense of pleasure from nitrous
      oxide therapy. A similar response was observed in the recall visits when the
      reactions of the children were compared with the reactions at the last dental
      appointment. It is concluded that the sense of pleasure is strengthened through
      the second visit, but that the sense of pleasure and ability to cope is
      overwhelmed by the inconvenience of the dental treatment at the third visit.

PMID- 9641093
TI  - Minimizing otitis media by manipulating the primary dental occlusion: case
      report.
AB  - Acrylic resin bonded to the occlusal surfaces of mandibular second primary molars
      was found to be an effective method to disclude the primary dentition and reduce
      or eliminate otitis media in young children between the ages of two to six years
      of age.

PMID- 9641095
TI  - Ectopic eruption of maxillary first permanent molars: treatment options and
      report of two cases.
AB  - Irreversible ectopic eruption of maxillary first permanent molars may lead to
      crowded permanent dentition when it is overlooked. The situation usually requires
      active treatment. In the presented irreversible ectopic eruption cases,
      distalization and uprighting of maxillary first permanent molars were achieved
      using removable orthodontic appliances.

PMID- 9641094
TI  - Open bite due to lip sucking: a case report.
AB  - Lip sucking, in spite of being less frequent than other habits, can cause
      malocclusion, which in turn may favor the appearance of other new habits such as
      tongue thrust. The elimination of this habit can lead to the spontaneous
      correction of malocclusion. The case report of a three-year-old male with a lip
      sucking habit is presented. After eliminating the habit, the open bite that it
      had caused, corrected spontaneously.

PMID- 9641096
TI  - Bonding mechanism of Compoglass to dentin in primary teeth.
AB  - This study evaluated the bonding mechanism of Compoglass compomer to dentin in
      primary teeth. Buccal or labial dentinal surfaces of 20 human extracted, non
      carious primary teeth stored in 4 degrees C physiological saline solution were
      obtained by grinding on silicon carbide paper (final grit 600). The specimens
      were divided into two groups of 10 teeth each: (1) unetched dentin, Compoglass
      SCA, Compoglass; and (2) dentin etched with 10% phosphoric acid (Etch-AII),
      Compoglass SCA, Compoglass. The Compoglass SCA and Compoglass compomer were
      placed according to the instructions of the manufacturer, except Group 2 were the
      dentin was first etched with 10% phosphoric acid for 30 seconds. Twenty-four
      hours after placing the compomer over the treated dentinal surface, the specimens
      were dehydrated with a series of alcohol and freon. Then critically point dried.
      The specimens were split with a chisel and the compomer/dentin interface
      evaluation was performed with the SEM. The results showed that when the
      instructions of the manufacturer were followed (Group 1) the compomer showed a
      very close relation to the dentin with some tag structures penetrating the
      dentin. When phosphoric acid etching preceded the compomer placement a hybrid
      layer with tags penetrating the dentin was noted in most specimens.

PMID- 9641097
TI  - Microleakage reduction from newer esthetic restorative materials in permanent
      molars.
AB  - Through use of new technologies, such as air-abrasive devices, caries detector
      dyes, modern technology can increase the speed, comfort and success of dental
      restorations. However the issue of marginal adaptation has been an ongoing
      technical problem. Today with the more frequent use of posterior composite
      resins, poor marginal adaptation of resin is still the major cause of failure of
      the restoration. Material contraction from polymerization and possibly
      inappropriate preparation design are key factors in the longevity of the
      restorations. This study attempts to determine the more effective material and
      technique for reducing microleakage in composite restorations. An in vitro study
      using three hybrid composite resins was done to evaluate marginal microleakage.
      Extracted molars were chosen and evaluated for caries through the use of caries
      detector dye. Using air-abrasion, caries were removed and minimal preparations
      were done. The samples were divided into two groups. First group was restored
      with Herculite XRV and Heliomolar paste composites resins. The second group was
      restored with Revolution flowable composite resin. Also Opti-bond and Fortify
      were used as a bonding agent and surface penetrating sealant respectively. The
      teeth were properly finished, thermocycled and evaluated for leakage using 2%
      basic fuschin detector dye. All data were subjected to the nonparametric Mann
      Whitney Rank Sum Test. The results revealed that Herculite XRV and Heliomolar
      paste composites had significantly higher microleakage formation (P < 0.03), and
      also they presented higher void formation (P < 0.0001) than Revolution flowable
      composite resin.

PMID- 9641098
TI  - Microleakage of fissure sealants after occlusal enameloplasty and thermocycling.
AB  - This study evaluated the microleakage of a filled and an unfilled sealant after
      different occlusal surface treatments. A total of 120 human non carious extracted
      molars were cleaned with a water slurry of fine flour of pumice using Crescent
      Snap-On pointed brushes in a slow-speed hand piece. The teeth were divided at
      random into six groups of 20 teeth each; Group 1 pumice prophylaxis and
      PrismaShield filled sealant; Group 2 pumice prophylaxis and Delton opaque
      unfilled sealant; Group 3 treatment with a diamond fissure bur (Sorensen Ponta
      K.G. 2137 F) and PrismaShield sealant; Group 4 treatment with a diamond fissure
      bur (Sorensen Ponta K.G. 2137 F) and Delton opaque sealant; Group 5 treatment
      with a 1/4 round carbide bur and PrismaShield sealant; and Group 6 treatment with
      a 1/4 round carbide bur and Delton opaque sealant. Before sealant placement, the
      enamel occlusal surfaces were acid-etched for 30 seconds using disposable
      brushes, rinsed, and dried. The sealants were light-cured for 40 seconds.
      Immediately after curing the sealant, 60 teeth were placed in distilled water for
      48 hours and 60 teeth were thermocycled (500x, at 5 degrees C - 55 degrees C,
      dwell time 30 seconds) and evaluated for microleakage. Wilcoxon and Fisher's
      Exact Test revealed no statistical significant difference in microleakage between
      the thermocycled and non-thermocycled groups, between the fissure treatment
      modalities or between the filled and unfilled sealants.

PMID- 9641099
TI  - Fluoride release from three different types of glass ionomer cements after
      exposure to NaF solution and APF gel.
AB  - The objective of this study was to evaluate the fluoride release from three
      different types of glass ionomer cements and the fluoride release after exposure
      to NaF solution and APF gel. After determining the fluoride release during 28
      days in artificial saliva, specimens were divided into two groups and exposed to
      NaF solution and APF gel for 2 min during 20 days. For each material, the release
      was highest during the first day, but Kromoglass released statistically
      significantly higher amounts of fluoride than the other. Vitrabond and Dyract
      followed in order. The differences in all groups were not statistically
      significant after third day. For statistical analysis: Paired- T Test, Variance
      Analysis and Duncan's Multiple Range Test were used. After exposure to NaF
      solution and APF gel all glass ionomer cements were recharged but the specimens
      exposed to APF gel were statistically significantly more recharged than NaF
      solution. As a result we conclude that glass ionomer cements can act as a
      rechargeable slow fluoride release systems and especially in caries active
      children, topical NaF applications with glass ionomer cements could be
      recommended as a preventive measure. We conclude that these results should be
      supported with long term and in vivo studies.

PMID- 9641100
TI  - Epidermolysis bullosa: case report of appropriate classification of subtype
      because of an early dental exam.
AB  - Epidermolysis bullosa is a unique group of disorders that have blister formation
      as the common feature. Although there are many variants of this disorder, the
      subtypes are classified into three groups based upon the level of tissue
      separation that occurs after mechanical trauma is sustained by the skin. Specific
      subtypes of EB may have substantial involvement of extracutaneous areas such as
      the oral cavity and dentition. This case report demonstrates the importance of a
      dental examination at an early age in order to facilitate the correct subtyping
      of EB. For the very young patient, correct classification of the subtype of EB
      may be very important in identifying the severity of clinical features associated
      with the disorder, and with this information the patient and family may become
      better aware of potential complications of the disorder such as the dental
      defects described in this report.

PMID- 9641101
TI  - Congenital absence of parotid glands and lacrimal puncta.
AB  - Bilateral parotid aplasia and lacrimal puncta are a rare disorder. A case is
      presented in which the clinical diagnosis was confirmed by ultrasonography. The
      importance to dentists in early recognition of bilateral parotid aplasia and
      lacrimal puncta is emphasized.

PMID- 9641102
TI  - Enamel hypoplasia and essential staining of teeth from erythroblastosis fetalis.
AB  - The dental, clinical, radiological, pedigree and dermatoglyphic findings of a
      patient showing hypoplasia of enamel and intrinsic staining of the teeth from
      erythroblastosis fetalis are presented.

PMID- 9641103
TI  - Leukemic children: clinical and histopathological gingival lesions.
AB  - The relation between leukemia and gingiva was investigated in the present study.
      An extensive tumor infiltration in the gingiva was established in 1 of 2 patients
      with acute leukemia (AML). An inflammatory cell infiltration in various degrees
      was noticed in total 28 patients with leukemia (L). Various degrees of epithelium
      hyperplasia in all patients existing in 14 patients with medium intensity and
      occurring in 14 patients with light intensity of hyperplasia were observed. An
      increase in the keratinization of epithelium, in 3 patients with medium intensity
      and 1 patient with light intensity was found. It was also seen that there were
      fungal infections in 3 patients with medium intensity, in 6 patients with light
      intensity and existing in a total 26 patients with acute lymphoblastic leukemia
      (ALL).

PMID- 9641104
TI  - Acute lymphoblastic leukemia: dental health of children in maintenance therapy.
AB  - The dental health of 41 children aged 4-16 years who were in maintenance therapy
      from acute lymphoblastic leukemia (ALL) was examined in relation to the period of
      time in maintenance. There was no significant difference in dental experience and
      salivary flow rate between the control group and patients with leukemia.
      Performed treatment index (PTI) and required treatment index (RTI) scores
      reflected that children, who were in maintenance therapy had insufficient dental
      care and needed more dental treatments. A statistically significant difference in
      salivary pH was found between the children, who were in maintenance therapy for
      12-24 months and less than 12 months and also the control group; but the pH
      scores of all groups were observed in normal limits.

PMID- 9641105
TI  - Dental anomalies caused by oncological treatment: case report.
AB  - In infancy, the oncological treatment is at times chemoradiotherapy. This
      treatment may cause dental development anomalies that can affect the form and
      structure of the tooth. A case report with this type of dental damage is
      presented.

PMID- 9641106
TI  - Effect of masticatory cycles on apical leakage of obturated teeth.
AB  - This study investigated the effect of apical leakage due to masticatory cycles on
      root canal treatment. Twenty upper maxillary molars were first obturated using
      the warm vertical compaction technique. Four maxillary casts were then built,
      with each holding four of the sample molars. The molars were embedded in resin
      with the roots separated from the resin by means of a light silicon. The four
      remaining teeth served as controls and were not submitted to occlusal forces. A
      mechanical device to simulate masticatory cycles subjected the teeth to 0.5 x
      10(6) cycles (group A), 10(6) cycles (group B), 2 x 10(6) cycles (group C), and 3
      x 10(6) cycles (group D); the control was group E. The roots were placed in 2%
      methylene blue dye solution for 72 h and then sectioned longitudinally so that
      dye penetration could be measured. The mean values of dye penetration were: 3.70
      +/- 0.69 mm, group A; 5.00 +/- 1.14 mm, group B; 6.00 +/- 1.01 mm, group C; 7.23
      +/- 0.66 mm, group D; and 2.74 +/- 0.75 mm, group E. The value of dye penetration
      increased in correlation with the number of masticatory cycles. This in vitro
      study suggests the significant effect of masticatory loads on apical leakage.

PMID- 9641107
TI  - Effect of calcium hydroxide on the dissolution of soft tissue on the root canal
      wall.
AB  - Calcium hydroxide [Ca(OH)2] paste can aid in the cleaning of a root canal because
      of its soft tissue-dissolving potential. In this study, we examined with a
      scanning electron microscope the dissolution by Ca(OH)2 paste of pulpal tissue
      attached to uninstrumented bovine root canal walls. Extracted bovine anterior
      teeth were divided into small specimens at the middle portion of the roots. The
      experimental groups were treated with sodium hypochlorite (NaOCl), Ca(OH)2, or a
      combination of Ca(OH)2 + NaOCl. The control group was given no treatment. The
      root canal walls were observed with a scanning electron microscope, and the
      amount of remaining pulp tissue was compared. The amount of debris was reduced
      remarkably in the groups treated with NaOCl for > 30 s, or Ca(OH)2 for 7 days.
      The combination of Ca(OH)2 + NaOCl was more effective than the separate
      treatments. The results suggest that Ca(OH)2 as a root canal medicine serves as
      an effective agent in removing tissue debris remaining on the root canal walls.

PMID- 9641108
TI  - Stimulatory effect of interleukin-6 on plasminogen activator activity from human
      dental pulp cells.
AB  - The plasminogen activator (PA)-plasmin proteolytic system has recently received
      considerable attention because of its participation in a wide variety of
      biological activities and in pathological conditions involving tissue
      destruction. We examined the effects of interleukin-6 (IL-6) on PA activity and
      the gene expressions of tissue type (t) PA and PA inhibitor-1 (PAI-1) in human
      dental pulp (HDP) cells. IL-6 treatment induced significantly high PA activity in
      the HDP cells in a time- and dose-dependent manner, compared with nontreated
      controls. Western-blot analysis showed that tPA protein in the conditioned medium
      was stimulated by IL-6, compared with the control. The tPA and PAI-1 mRNA levels
      were increased in HDP cells treated with IL-6, as shown by reverse transcriptase
      polymerase chain reaction. These results suggest that IL-6 stimulated PA activity
      through an enhancement of tPA gene expression and may be involved in
      extracellular matrix degradation through the stimulation of the PA-plasmin system
      of HDP cells.

PMID- 9641109
TI  - Biocompatibility of two apatite cements.
AB  - Biocompatibility and osteogenic potential of two calcium phosphate cements (G-5
      and G-6) and Super-EBA were investigated by subcutaneous and intraosseous
      implantation in 90 rats. Reactions were studied microscopically at 15, 30, and 60
      days after implantation. Super-EBA was well tolerated by both soft and hard
      tissues. G-5 was highly biocompatible with resorption and bone replacement at
      intraosseous implantation sites. G-6 promoted moderate inflammation and a foreign
      body giant cell response over the 60-day study period. None of the materials
      elicited osteogenesis or dystrophic calcification at the subcutaneous
      implantation sites.

PMID- 9641110
TI  - Apical sealing ability of glass ionomer sealer with and without smear layer.
AB  - The effect of two different root canal cements and removal of the smear layer on
      the apical seal in roots obturated with Thermafil obturators was tested. Thirty
      extracted human mandibular first molars with 60 canals (mesial roots) were
      instrumented with the use of a step-back technique. Teeth were placed into 6
      groups of 10 canals each. The first three groups had the smear layer removed with
      EDTA and NaOCl, and the other three groups were irrigated with NaOCl only. Canals
      were obturated using Thermafil without sealer cement or Thermafil with Ketac-Endo
      or Thermafil with zinc oxide-eugenol cement. All roots were placed in India ink
      for 4 days. The roots were cleared, and the degree of linear dye penetration was
      measured. The study showed that root canal cement significantly improved the
      apical seal of the Thermafil obturation technique (p < 0.05), whether the smear
      layer was removed or not. The apical seal exhibited by Ketac-Endo was not
      significantly different from that provided by zinc oxide-eugenol cement (p >
      0.05), regardless of the presence or absence of a smear layer.

PMID- 9641111
TI  - Influence of the concentration of ions and foramen diameter on the accuracy of
      electronic root canal length measurement--an experimental study.
AB  - Investigations on the concentration of cations in human pulp have shown that
      pathological changes in the pulp lead to changes in the concentration of ions in
      the tissue. Consequently, its electrophysiological characteristics are changed,
      which affects the accuracy of electronic root canal length measurements (ERCLMs).
      The aim of this study was to examine the effect of concentrations of Na+, K+, and
      Ca2+ cations in medium within the canal and around the tooth, and also foramen
      diameter, on the accuracy of ERCLMs. The model comprised 21 extracted single
      rooted human teeth divided into two experimental groups and one control group,
      with seven teeth each. Two aqueous solutions of different concentrations of NaCl,
      KCl, and CaCl2 were mixed with agar. The concentrations of Na+, K+, and Ca2+
      corresponded to the results of analyses performed by atomic spectrophotometry on
      the extirpated human pulps. Agar containing cations was injected into the root
      canal prepared with a foramen diameter of 0.25 mm. In the control group, the
      teeth were then completely immersed in agar of the same concentration of cations
      as the agar inside the canal. In the first experimental group (group 1), the
      concentration of ions was higher inside the canal, compared with the
      concentration outside the canal. In the second experimental group (group 2), the
      order of concentrations was inverse. In all three groups, ERCLMs was performed in
      the previously described model. Then, the size of the apical foramens was
      enlarged and ERCLMs repeated at foramen diameters of 0.45 mm and 0.70 mm
      diameters, respectively. Results indicate that at 0.25 diameters, the most
      accurate measurements were taken when the concentrations of ions inside the canal
      were higher than outside the canal (Xdif = 1.39 +/- 1.21 mm) (group 1). At
      diameters of 0.45 and 0.70 mm, no significant differences were found (p < 0.05)
      between the experimental groups (error amounted to Xdif = 6.27 +/- 1.47 mm). In
      the control group measurement, error increased with enlargement of the foramen.

PMID- 9641112
TI  - Effects of pulsed Nd:YAG laser irradiation on root canal wall dentin with
      different laser initiators.
AB  - The effects of pulsed Nd:YAG laser irradiation with different laser initiators on
      the permeability and ultrastructure of the root canal wall dentin were
      investigated in vitro. Forty extracted human single-rooted teeth were randomly
      assigned to four groups. Group 1 teeth were not lased as a control. Group 2
      specimens received four 10-s duration laser exposures for a total exposure of 40
      s/canal. In group 3 specimens, the root canals were painted with black ink and
      then lased by the same method as group 2 teeth. In group 4 specimens, root canals
      were treated with 38% Ag(NH3)2F and then lased by the same method as group 2
      teeth. Laser parameters were set at 2 W, 20 pps. After being placed in 0.6%
      rhodamine B solution for 48 h, the teeth were sectioned for study by stereoscope
      and scanning electron microscopy. Statistical analysis showed there were
      significant differences (p < 0.05) in dentin permeability in the apical areas
      between groups 3 and 1, 4 and 1, and 4 and 2. Scanning electron microscopic
      examination showed that laser treatment alone had no obvious effects on the root
      canal wall. The root canal surfaces prepared for by laser irradiation with black
      ink or 38% Ag(NH3)2F revealed melting, smear layer evaporation, and open dentinal
      tubules. Black ink was more effective than 38% Ag(NH3)2F as a Nd:YAG laser
      initiator.

PMID- 9641113
TI  - Black-pigmented bacteria in coronal and apical segments of infected root canals.
AB  - Black-pigmented bacteria (BPB) have been associated with infections of endodontic
      origin. The purpose of this study was to culture and identify BPB from the apical
      and coronal segments of infected root canals to understand better their
      ecological relationships. Teeth with a periapical radiolucency were extracted and
      immediately placed in reduced transport fluid for transport to an anaerobic
      chamber. Of 18 sampled roots, 12 were positive for the growth of BPB. Eight of
      the 12 roots with BPB had a carious exposure of the pulp chamber. Seven roots had
      Prevotella nigrescens in both the apical and the coronal segments. Six of these
      seven teeth had carious exposures of the pulp chamber. Of the 12 roots infected
      with BPB, six roots had two different species of BPB, with P. nigrescens always
      being one of the species. P. nigrescens was the most often isolated BPB from both
      the coronal and apical segments of infected root canals.

PMID- 9641114
TI  - In vitro study of a Nd:YAP laser in endodontic retreatment.
AB  - Nd:YAP laser is a dental laser with a 1340 nm wavelength. The laser beam is
      carried by a 200 to 300 microns fiberoptic and is suitable for endodontic
      therapy. We used the Nd:YAP laser in an in vitro experiment to study its
      effectiveness in endodontic retreatment. Temperature measurements and irradiation
      parameters were first defined. Then Nd:YAP laser irradiation was used, alone or
      in combination with hand instruments, to remove various canal sealers and broken
      instruments. Clinical parameters were monitored and scanning electron microscopic
      observations were conducted. When used at 200 mJ--with a pulse duration of 150
      ms, an exposure time of 1 s and a frequency of 10 Hz--Nd:YAP laser preserved the
      dentinal walls of the root canal and enabled root canal retreatment without
      thermic elevation harming periodontal tissue. It is concluded that, in
      combination with hand instruments, the Nd:YAP laser is an effective device for
      root canal preparation in endodontic retreatment.

PMID- 9641115
TI  - Comparison of the performance of four files with rounded tips during shaping of
      simulated root canals.
AB  - A total of 160 simulated canals of various angles and positions of curvature were
      prepared by hand using either Mani Flexile Files, Mani SEC-O Files, Maillefer
      Flexofiles, or Zipperer Flexicut Files. After orifice enlargement, each file type
      was used to prepare 40 canals employing a balanced force motion and a modified
      double-flared technique. Pre- and postoperative images of the canals were taken
      with a videocamera, and stored and manipulated in a computer with image analysis
      software. The presence of canal aberrations and the amount of material removed as
      a result of preparation were determined from composite images of superimposed pre
      and postoperative views. Significant differences (p < 0.001) in preparation time
      were observed, with Flexile Files being quickest and SEC-O Files being slowest.
      Overall, Flexofiles and Flexicut Files deformed significantly more (p < 0.001)
      than Flexile and SEC-O Files. The incidence of canal blockage was not influenced
      by instrument type, but the incidence of apical extrusion was significantly
      greater (p < 0.001) with SEC-O Files. SEC-O Files created significantly fewer (p
      < 0.001) and significantly narrower (p < 0.001) zips, with significantly less (p
      < 0.001) removal of material from the outer aspect of the curve and thus
      significantly less (p < 0.001) transportation. Flexicut Files created the widest
      canals apically, with the greatest removal of material from the outer aspect of
      the curve and the most transportation. Flexofiles created significantly more (p <
      0.001) perforations. Under the conditions of this study, obvious differences
      between instruments were highlighted with SEC-O Files preparing canals more
      safely and with least destruction. The unique rounded tip of the SEC-O Files may
      have had an influence on the outcome.

PMID- 9641116
TI  - The C-shaped mandibular second molar: incidence and other considerations. Members
      of the Arizona Endodontic Association.
AB  - Although its most common configuration is two roots and three canals, the
      mandibular second molar may have many different combinations. Cooke and Cox were
      the first to describe a single-rooted mandibular second molar with a continuous
      slit connecting some or all of the canals. If sectioned horizontally through the
      main portion of the root, this slit had the shape of the letter "C." Other papers
      were written and lectures were presented on this and similar entities, but its
      frequency and significance have remained the object of speculation because large
      numbers of these teeth have not been categorized. By combining the efforts of an
      endodontic study club, 811 endodontically treated mandibular second molars were
      evaluated. Sixty-two of these (7.6%) were identified as C-shapes. Other aspects
      of this configuration were also investigated.

PMID- 9641117
TI  - Endodontic therapy in a maxillary second molar with three buccal roots.
AB  - In this study, we report a case of a four-rooted maxillary second molar in which
      three well-separated buccal roots were located. This case demonstrated that even
      though it is not common, an extra root containing an independent root canal may
      occur.

PMID- 9641118
TI  - Conservative treatment of supernumerary maxillary incisor with dens invaginatus.
AB  - A case report is presented describing the treatment of a right maxillary
      supernumerary incisor with dens invaginatus. Extensive caries penetration into
      the invagination space was subsequently followed by contamination of the included
      tissue, but no pulp pathosis has been detected. The purpose of this case report
      was to present a treatment modality that enabled the preservation of pulp
      vitality by a conservative endodontic approach. Clinical considerations and
      treatment are discussed and reported.

PMID- 9641119
TI  - Surgical extrusion of a completely intruded permanent incisor.
AB  - This report presents a case of a completely intrusive luxation of a mature
      permanent central incisor in a 10-yr-old boy. The intruded tooth was repositioned
      by using surgical extrusion and stabilization with interdental sutures.
      Endodontic treatment was performed with calcium hydroxide paste as the intracanal
      medication and a calcium hydroxide-based root canal sealer. This treatment mode
      was observed at 18 months and was successful at that time.

PMID- 9641120
TI  - Risk assessment of the toxicity of solvents of gutta-percha used in endodontic
      retreatment.
AB  - Three randomly assigned groups of single-canaled extracted teeth obturated with
      gutta-percha were retreated using controlled application of one of three organic
      solvents: chloroform, xylene, or halothane. Two additional groups of teeth served
      as positive and negative controls. Residual volume of solvent expressed through
      the apical foramen during retreatment was determined by the difference of
      pretreatment and posttreatment weights of hermetically sealed receptacles
      attached to the root surface of the teeth. Results indicate that the amount of
      solvent that has been determined to have leached out through the apical foramen
      is several orders of magnitude below the permissible toxic dose. Thus, it is
      proposed that the use of any of the aforementioned solvents used in the
      retreatment of root canals would pose negligible risk to the patient.

PMID- 9641121
TI  - Analysis of forces developed during obturations. Wedging effect: Part I.
AB  - The aim of this study was to define the "wedging effect" created by the
      intracanal forces developed during obturations and to measure it using a force
      analyzer device. In endodontics, the wedging effect is the result of, for
      example, a plugger pushing gutta-percha into a canal: the plugger functions much
      as the rod of a hydraulic jack and the vertical force applied by this rod induces
      in the cylinder (i.e. the canal) a hydrostatic pressure that is relatively equal
      in all directions. It is these forces resulting from the hydrostatic pressure
      that have been labeled the wedging effect. The original device, the Endographe,
      had a monobloc cupule for measuring the external vertical and horizontal forces
      developed by a practitioner, but it was unable to measure the intracanal forces.
      With a new cupule composed of two independent parts joined under pressure, the
      wedging effect was recorded and analyzed. Two obturation methods, warm vertical
      compaction and lateral condensation, were performed by endodontists. The forces
      were depicted by Endogrammes as a function of time. For all of the forces
      developed during the two techniques, the mean values showed a nonsignificant
      difference between the different practitioners. The use of graphs provides a new
      approach to the analysis of intracanal forces as they develop our time and
      permits the comparison of different obturation techniques.

PMID- 9641122
TI  - Analysis of forces developed during obturations. Wedging effect: Part II.
AB  - The aim of this study was to use a force analyzer device, the modified Endographe
      with a new cupule, to compare the forces and wedging effects developed in the
      root canal using four obturation techniques: warm vertical compaction, lateral
      condensation, thermomechanical compaction, and Thermafil condensation. The
      different methods--that varied in instrumentation, duration, and compaction load-
      were studied from graphs representing the force application sequences. In
      addition, the graphs resulting from modifications in technique (such as using an
      undersized spreader and pluggers that were either too small or too big) and
      deliberately induced failures in technique (by use of a too small condenser or a
      too small master cone) were studied. The mean values for the wedging effect for
      warm vertical compaction, lateral condensation, thermomechanical compaction, and
      Thermafil condensation were, respectively, 0.65 +/- 0.07 kg, 0.8 +/- 0.1 kg, 0.6
      +/- 0.08 kg, and 0.03 +/- 0.01 kg. The use of graphs provides a new approach to
      the analysis of obturation techniques.

PMID- 9641123
TI  - The effect of the bleaching agent sodium perborate on macrophage adhesion in
      vitro: implications in external cervical root resorption.
AB  - The purpose of this study was to investigate the in vitro effect of sodium
      perborate, which is used as a bleaching agent in the treatment of discolored
      pulpless teeth, on substrate adherence capacity of macrophages. Inflammatory
      macrophages were obtained from Wistar rats and resuspended in RPMI-1640 medium.
      As a test of macrophage adhesion, the adherence capacity of macrophages to a
      plastic surface was determined. Assays were conducted in Eppendorf tubes for 15
      min of incubation at 37 degrees C in a humidified atmosphere of 5% CO2. The
      adherence index was calculated. Results showed that sodium perborate decreased in
      a dose-dependent manner and decreased significantly (p < 0.05) the adherence
      index of rat peritoneal macrophages. Sodium perborate was less potent than sodium
      hypochlorite and eugenol in inhibiting macrophage adhesion. The inhibitory effect
      of sodium perborate on macrophage adhesion further supports the concept that this
      agent is not implicated in external cervical root resorption associated with
      intracoronal bleaching.

PMID- 9641124
TI  - Development of an anaerobic bacterial leakage model.
AB  - The majority of bacteria associated with infections of endodontic origin are
      strict anaerobes. The purpose of this study was to develop an endodontic
      microleakage model using strict anaerobic bacteria in a two-chamber system. Nine
      species of anaerobic bacteria were tested for viability and detection by either
      turbidity or color change of the broth. A survey of pH chromogenic substrates
      revealed that bromcresol purple (pH 5.2 = yellow, pH 6.8 = purple) could be used
      as a chromogenic indicator to detect the growth of anaerobic bacteria. Peptone
      yeast extract-glucose broth (PYG) and brain heart infusion broth (BHI) were each
      used alone and with bromcresol purple (bpPYG, bpBHI) in this study. Fusobacterium
      nucleatum and F. necrophorum were viable in all four media for > 2 wk and
      produced both turbidity and a color change after only 1 day of incubation.
      Veillonella parvula in either bpBHI or BHI and Peptostreptococcus anaerobius in
      either bpPYG or BHI were viable for > 2 wk and showed a color change or turbidity
      after 1 or 2 days. The results indicate that leakage of strict anaerobes may be
      evaluated in a two-chamber system.

PMID- 9641125
TI  - pH measurement of root canal sealers.
AB  - The purpose of this study was to compare the surface pH level of three different
      type sealers after mixing at various time intervals in vitro. The cements were
      mixed according to the manufacturer's instructions. They were incubated to set in
      100% humidity at 37 degrees C for 1 h, 24 h, 5 days, 8 days, 2 wk, 3 wk, 4 wk, 5
      wk, and 7 wk. pH was calculated by a Twin pH meter. The pH levels of the three
      sealers were different at various time intervals (p < 0.0001). The resin-based
      cement had a acid pH level (pH < 7.0). The calcium hydroxide-based cement showed
      a higher alkalinity pH level (pH > 7.0). The zinc oxide-eugenol-based cement
      showed a similar pH level to the calcium hydroxide cement at the end of the
      measurement. We postulated that, in endodontic therapy when those healing is
      needed, the alkaline-based sealer is the choice.

PMID- 9641126
TI  - The effect of 4% titanium tetrafluoride solution on root canal walls--a
      preliminary investigation.
AB  - The aim of the present study was to evaluate the effect of 4% titanium
      tetrafluoride (TiF4) solution on root canal walls by scanning electron
      microscopy. Twenty four root canals with or without a smear layer were treated
      with 4% TiF4 solution. Scanning electron microscopic observation of the smeared
      canal walls showed that TiF4 solution modified the smear layer and produced a
      massive structure. In smear-free group, a granular coating was formed on
      intertubular and intratubular dentin. The stability of this layer was tested
      further with EDTA and/or NaOCl irrigations on 20 additional specimens. It was
      observed that none of the solutions was able to remove this modified smear layer.
      These results may indicate that this extremely stable structure may be
      advantageous in endodontics, because it can prevent further infection of root
      canal dentin by sealing off the tubules permanently, and can reduce microleakage
      by preventing further dissolution and disintegration of the smear layer.

PMID- 9641127
TI  - Physical properties of CH61, a newly developed root canal sealer.
AB  - This study was performed to evaluate the physical properties (sealing, flow,
      radio-opacity, working time, and solubility) of a newly developed root canal
      sealer, CH61. It was compared with Canals, Sealapex, and AH26, which are typical
      commercially available root canal sealers. The sealing ability was evaluated by
      dye penetration. The flow was evaluated by two methods. One was flow in the
      vertical dimension, and the other was disk diameter. Radio-opacity, working time,
      and solubility were performed in accordance with the standards of the
      International Organization for Standardization. No dye penetration after
      immersion for 24 h was noted. In CH61, and there were significant differences
      between the values for CH61 and Canals, Sealapex, or AH26 (p < 0.001). For flow,
      the results differed from method to method. The radio-opacity decreased in the
      following order: AH26, Canals, CH61, and Sealapex. The solubility was the lowest
      for CH61. This study showed that CH61 had excellent sealing properties and low
      solubility.

PMID- 9641128
TI  - The CO2 laser as an aid in direct pulp capping.
AB  - Two hundred direct pulp capping procedures were conducted in the present study.
      One hundred of them were performed with the CO2 laser, and 100 were conducted
      conventionally as a control by using a calcium hydroxide preparation. Follow-up
      examinations were performed after 1 wk and monthly for 12 months after treatment.
      Thermal tests were used for vitality assessments and laser Doppler flowmetry for
      direct measurement of pulpal blood. In the group of pulps treated with the CO2
      laser, the last recall examination at 12 months demonstrated that 89 teeth
      remained vital, corresponding to a success rate of 89%. In the control group, the
      success rate was considerably lower (68%). Exposure sizes and mean patient age
      were nearly identical in both groups. The CO2 laser seems to be a valuable aid in
      direct pulp capping.

PMID- 9641129
TI  - Stimulation of interleukin-6 production in human dental pulp cells by
      peptidoglycans from Lactobacillus casei.
AB  - Interleukin-6 (IL-6), which is a multifunctional cytokine, has an important role
      in acute and chronic inflammation. The peptidoglycan (PG) was purified from
      Lactobacillus casei, which was a Gram-positive bacteria frequently isolated from
      deep carious lesions and suspected to be a pathogen of pulpitis. In this study,
      the effects of PG on the production of IL-6 in human dental pulp cells were
      examined. PG stimulated IL-6 production in a time- and dose-dependent manner.
      Reverse transcriptase-polymerase chain reaction experiments showed that the
      increase was dependent on the enhancement of IL-6 mRNA levels. These findings
      suggest that Gram-positive bacteria, such as L. casei, from carious lesions,
      might be involved in developing pulpitis through the stimulation of IL-6
      production.

PMID- 9641130
TI  - Strengthening immature teeth during and after apexification.
AB  - The purpose of this study was to evaluate the strengthening effect of an internal
      resin bonding technique. One hundred central incisors were endodontically treated
      and divided equally into five groups. Group 1, without any cervical preparation
      and with access repaired with bonded resin, served as the positive control. Teeth
      in groups 2 to 5 were cervically prepared to simulate the thin dentinal wall of
      immature teeth, and obturation material was removed to 3 mm below the
      cementoenamel junction (CEJ). In group 2, the negative control, the access was
      restored with bonded composite to the level of the CEJ. In group 3, access was
      restored with composite resin 3 mm apical to the CEJ using a clear post system.
      Group 4 was treated similarly to group 3, but an opaque post replaced the clear
      post. Group 5 was treated like group 3, after which a metal post was cemented
      into the channel left after removal of the clear post. All teeth were subjected
      to compression testing and the force required to fracture the teeth cervically
      was recorded for each group and the Kruskal-Wallis analysis performed to detect
      intergroup differences. All of the bonded resin techniques significantly
      strengthened the teeth against fracture, compared with the negative control group
      (p < 0.05). None of the experimental groups (3-5) were significantly different
      from the positive control group.

PMID- 9641131
TI  - Surgical endodontics of upper molars: relation to the maxillary sinus and
      operation in acute state of infection.
AB  - Findings in 200 cases of root resection of first maxillary molars showed
      perforation to the sinus in half of the cases. In 42% of the cases, the first
      maxillary molar had root resection performed in a subacute or acute state of
      infection. Only two cases developed postoperative sinusitis. Antibiotic treatment
      was indicated preoperatively in 3% and postoperatively in 5%. Postoperative
      symptoms, such as pain and swelling, were usually moderate, possibly because of a
      nontraumatizing operation technique, a careful removal of infected tissue, and a
      good drainage by loose suturing.

PMID- 9641132
TI  - Interpretation of periapical lesions comparing conventional, direct digital, and
      telephonically transmitted radiographic images.
AB  - The purpose of this study was to evaluate direct digital radiography (DDR) and
      telephonically transmitted images versus conventional radiography in the
      interpretation of artificial periapical bone lesions. Five teeth were chosen from
      four cadaver jaw specimens. Three types of DDR images were evaluated: DDR stored
      images, DDR transmitted images, and DDR reversed images. A total of 150 DDR
      computer monitor images and 56 D-speed film images were evaluated by three
      endodontists and one endodontic graduate student. The Wilcoxon signed-ranks test
      was used for statistical analyses of the results. DDR reversed images were
      statistically inferior to DDR stored images, DDR transmitted images, and
      conventional radiography images (p < 0.0001). There were no statistically
      significant differences between DDR stored images, DDR transmitted images, and
      conventional film images in the ability of the evaluator to identify artificial
      periapical bone lesions (p > 0.05).

PMID- 9641133
TI  - Metastatic carcinoma to the mandible that mimicked pulpal/periodontal disease.
AB  - An oral cavity metastasis from a poorly differentiated carcinoma, presumed to
      have originated in the pancreas, mimicked a dental abscess. An additional
      metastasis to the lung caused a postobstructive lobar pneumonia that masked the
      lesion, thereby delaying the diagnosis of malignancy. This case report
      illustrates how the clinical manifestations of a widely disseminated neoplasm led
      to initial medical confusion and subsequent dental misdiagnosis, and serves to
      caution of a possible pitfall in the dental evaluation of endodontic lesions.

PMID- 9641134
TI  - American Association of Endodontists' 55th Annual Session. New York, May 6-10,
      1998. Abstract.

PMID- 9641135
TI  - Scanning electron microscopic study of dentin lased with argon, CO2, and Nd:YAG
      laser.
AB  - The purpose of this study was to compare morphological changes on the dentin
      surface induced by laser light delivered perpendicular or parallel to the dentin
      surface. The surface of the dentin slices and the root canal walls were lased
      with argon, CO2, and Nd:YAG lasers. When the laser beam was parallel to the
      dentin, the effects of the laser energy ranged from no effect to eroding and
      melting of the smear layer and dentin in the samples. When the laser beam was
      perpendicular to the surface, all three lasers produced well-shaped craters. From
      this, it was concluded that the angle of the laser beam in relation to the target
      surface can be a deciding factor of how much energy will be absorbed by the
      dentin and consequently of the morphological changes induced by the laser.

PMID- 9641136
TI  - In vivo comparison of the biocompatibility of two root canal sealers implanted
      into the subcutaneous connective tissue of rats.
AB  - The purpose of this study was to evaluate the in vivo biocompatibility of Apexit
      (a calcium hydroxide) and Pulp Canal Sealer (a classic zinc oxide-eugenol), root
      canal sealers, after implantation in rat connective tissue. Forty-four white
      female Wistar-Furth rats were used. Each sealer was placed in Teflon tubes and
      implanted into specific dorsal subdermal tissues sites. Implants were removed
      after 5, 15, 60, and 120 days; fixed; and histologically prepared for
      microscopical evaluation. Severe inflammatory reactions with differing extensions
      of necrosis were observed with Apexit on the 5th and 15th days. The intensity of
      the reaction had diminished by the 60th day, and this reduction continued
      progressively through the 120th day. It was characterized by the presence of
      connective tissue with a few macrophages. Moderate to severe inflammation with
      confined areas of necrosis was observed in the Pulp Canal Sealer specimens on the
      5th day. The intensity of the reaction diminished by the 15th, 60th, and 120th
      days, but remained slightly greater than Apexit through longterm observation
      periods.

PMID- 9641137
TI  - Endodontic pathogens stimulate monocyte chemoattractant protein-1 and interleukin
      8 in mononuclear cells.
AB  - Microbial infection of the dental pulp leads to the recruitment of leukocytes and
      the formation of lesions of endodontic origin. The chemokines interleukin-8 (IL
      8) and monocyte chemoattractant protein-1 (MCP-1) are relatively specific
      chemoattractants for neutrophils and monocytes, respectively. In the present
      studies, peripheral blood mononuclear cells were stimulated by Streptococcus
      mutants, Porphyromonas endodontalis, and Peptostreptococcus anaerobius, which are
      associated with lesions of endodontic origin. Each of these bacteria induced a
      dose-dependent increase in IL-8 and MCP-1, determined by ELISA. The levels
      induced are physiologically relevant. However, low doses of P. endodontalis were
      less effective in inducing IL-8 or MCP-1 expression, compared with S. mutants or
      P. anaerobius. Thus, these bacteria can induce significant levels of the
      chemokines IL-8 and MCP-1, which could contribute to the recruitment of
      neutrophils or monocytes in vivo. The expression of these mediators may
      contribute to the development of endodontic infections, particularly with regard
      to inflammatory leukocyte recruitment.

PMID- 9641139
TI  - Cutting efficiency of a mid-infrared laser on human enamel.
AB  - In this study, the cutting ability of a newly developed dental laser was compared
      with a dental high-speed handpiece and rotary bur for removal of enamel.
      Measurements of the volume of tissue removed, energy emitted, and time of
      exposure were used to quantify the ablation rate (rate of tissue removal) for
      each test group and compared. Cutting efficiency (mm3/s) of the laser was
      calculated based on the mean volume of tissue removed per pulse (mm3/pulse) and
      unit energy expended (mm3/J) over the range of applied powers (2, 4, 6, and 8 W).
      The specimens were then examined by light microscopy and scanning electron
      micrographs for qualitative analysis of the amount of remaining debris and the
      presence of the smear layer on the prepared enamel surface. Calculations of the
      cutting efficiency of the laser over the range of powers tested revealed a linear
      relationship with the level of applied power. The maximum average rate of tissue
      removal by the laser was 0.256 mm3/s at 8 W, compared with 0.945 mm3/s by the
      dental handpiece. Light microscopy and scanning electron micrograph examinations
      revealed a reduction in the amount of remaining debris and smear layer in the
      laser-prepared enamel surfaces, compared with the conventional method. Based on
      the results of this study, the cutting efficiency of the high-speed handpiece and
      dental bur was 3.7 times greater than the laser over the range of powers tested,
      but the laser appeared to create a cleaner enamel surface with minimal thermal
      damage. Further modifications of the laser system are suggested for improvement
      of laser cutting efficiency.

PMID- 9641138
TI  - Cytotoxicity of endodontic materials.
AB  - An in vitro cell culture model of human gingival fibroblasts and L-929 cells was
      used to measure the cytotoxicity of currently used root canal sealers Endomet,
      CRCS, and AH26 and root-end filling materials Amalgam, Gallium GF2, Ketac Silver,
      mineral trioxide aggregate (MTA), and Super-EBA. Cytotoxic effects were assessed
      using the MTT assay for mitochondrial enzyme activity and the CV assay for cell
      numbers. Using inserts culture and L-929 fibroblasts. All-Bond-2 was also
      evaluated. The statistical analysis of results showed that CRCS was the least
      cytotoxic sealer followed by Endomet and AH26. Among root-end filling materials,
      MTA was not cytotoxic; Gallium GF2 displayed little cytotoxicity; and Ketac
      Silver, Super-EBA, and Amalgam showed higher levels of cytotoxicity. All Bond-2
      also displayed a high degree of cytotoxicity. CRCS was the best root canal sealer
      and MTA the best root-end filling material. The outcome was favorable also for
      Gallium GF2 as a retrofilling material.

PMID- 9641140
TI  - A comparison of amounts of apically extruded debris using handpiece-driven nickel
      titanium instrument systems.
AB  - One hundred single-rooted teeth were instrumented with Lightspeed, Profile .04
      Taper Series 29, and NT McXIM instruments according to the recommendations of the
      manufacturers, and Flex-R files using the balanced force technique. Groups were
      comparable with respect to average curvature, canal length, and major and minor
      foramen size. A standard amount of irrigant was used for each tooth. Apically
      extruded debris and irrigant were collected and weighed. Debris was desiccated
      before being weighed. There were no statistically significant differences among
      the four groups with respect to total extruded debris. The amount of extruded
      debris was positively correlated with the amount of irrigant extruded. Factors
      such as canal length, curvature, and foramen size did not affect the amount of
      debris extruded.

PMID- 9641141
TI  - Analysis of stress distribution in a maxillary central incisor subjected to
      various post and core applications.
AB  - In this study, stress distribution in a maxillary central incisor that was
      subjected to endodontic treatment and various post and core applications was
      determined by using a three-dimensional finite-element method. Cast gold post and
      gold core and different combinations of prefabricated stainless steel post, or a
      prefabricated titanium post with amalgam or composite cores were considered. In
      all cases, the tooth was assumed to have a porcelain crown. The primary purpose
      of the study was to evaluate the stress distribution due to simulated biting
      forces and thus investigate the reliability of different post and core
      applications. It was found that, within the limitations of the study, the cast
      gold post and gold core application yielded the best result. The second purpose
      of the study was to highlight the importance of using a unique stress value,
      which contains the effects of all the possible stress components existing upon
      loading in the determination of a possible failure. A resultant stress value and
      all the constituent components were shown in detail, and it was proved that an
      estimation independently based on an individual component might lead to erroneous
      results.

PMID- 9641142
TI  - In vitro adhesion of two strains of Prevotella nigrescens to the dentin of the
      root canal: the part played by different irrigation solutions.
AB  - Blocks of bovine incisor dentin, on the root canal surface of which a smear layer
      had been formed, were inoculated in vitro with two strains of Prevotella
      nigrescens, a wild sampled strain and a reference one (NCTC 9336). Half the
      blocks were pretreated with irrigating solutions: 6% citric acid for 5 min +
      6.25% sodium hypochlorite for 10 min. They were compared with the other blocks
      simply rinsed in distilled water (i.e. the control samples). The bacteria
      adhering to the dentin surface after an incubation time of 3 h were counted by
      direct examination using a scanning electron microscope. The adhesion of P.
      nigrescens was less marked on all of the samples treated with irrigating
      solutions. Adherence was particularly significant in the case of the wild strain
      (F = 10.22). The latter was far more active than the reference strain (F =
      35.82). The use of a chelating agent at the end of root canal preparation served
      to remove the smear layer and limited the attachment of P. nigrescens to the
      dentin.

PMID- 9641143
TI  - Balance of interleukin-1 beta and interleukin-1 receptor antagonist in human
      periapical lesions.
AB  - Interleukin-1 beta (IL-1 beta) has been considered as a major potent mediator of
      bone resorption and implicated in the development of human periapical lesions.
      Among naturally occurring interleukin-1 (IL-1) inhibitors, IL-1 receptor
      antagonist (IL-1ra) is a 22 kDa protein that shares homology with IL-1 beta and
      IL-1 alpha, binds to IL-1 receptor with similar affinity to IL-1, and has no
      known agonist properties. In this study, we measured the periapical exudate (PE)
      levels of IL-1 beta and IL-1ra from human periapical lesions. PE samples were
      collected from root canals during routine endodontic treatments, and the enzyme
      linked immunosorbent assay was used to measure PE-IL-1 beta and IL-1ra.
      Detectable levels of both IL-1 beta and IL-1ra were found in 25 of 29 clinical
      samples. Relatively high levels of IL-1ra compared with IL-1 beta (mean IL-1ra:IL
      1 beta ratio = 128:7; range: 0.9 to 495.4), and significantly positive
      correlation between IL-1ra and IL-1 beta levels was found. The PE-IL-1ra:IL-1
      beta ratios obtained from symptomatic lesions were significantly lower than those
      from asymptomatic lesions. These results suggest that IL-1ra-mediated IL-1
      antagonism occurred to block locally produced IL-1 activity, and the balance of
      IL-1 to IL-1ra production may be crucial in the development of periapical
      lesions.

PMID- 9641144
TI  - In vitro evaluation of the reliability of the Endex electronic apex locator.
AB  - A new generation of electronic apex locators (Endex) that operates in moistened
      canals has been developed lately. An experimental comparison of this apparatus
      with the real, tactile, and radiographic measurements of the root canal length
      has been conducted. Results show that tactile determination is highly inaccurate
      and that the Endex is as accurate as radiographic measurements. It also
      demonstrates that the nonreproducibility of radiographic measurements is
      statistically significant, whereas that of the Endex is not significant.

PMID- 9641145
TI  - The effect of instrument precurving on transportation in simulated curved canals.
AB  - The results of instrumentation studies in small curved canals using various
      instruments and techniques are not consistent. The amount of instrument
      precurving and a gradual or abrupt curve of the canal may have influenced the
      results of these studies. One hundred sixty resin blocks with simulated canals
      were used. Eighty blocks had gradual (GC) 30 degree curves, the remainder had
      abrupt (AC) 30 degree curves. Ten blocks for each curvature and for each degree
      of precurving amount (0, 15, 20, 25, 30, 35, 40, or 45 degrees) were instrumented
      with a machine that imparted only an in and out motion. The simulated canals were
      size 30 at the apex, and size 30 stainless steel K-files were used to instrument
      the canals. A transportation ("t") index was determined at two levels: T1 (1 mm
      from the apex) and TB (a line bisecting the curve of the canal). For GC at T1 and
      TB, 40- and 20-degree curved instruments respectively produced significantly less
      transportation than all other curvatures (p < 0.0001). For AC at T1 and TB, 35
      and 25 degree instruments respectively produced significantly less transportation
      than all other curvatures (p < 0.0001). Comparing GC and AC, the transportation
      for AC was significantly less (p < 0.0015).

PMID- 9641146
TI  - A study of the dental pulp cavity of mandibular first permanent molars in the
      Kuwaiti population.
AB  - This study documented the complexity of the root canal system in the mandibular
      first permanent molar. Forty-nine plastic replicas were used from mandibular
      first permanent molars obtained from young Kuwaitis. Results revealed that the
      tooth had 2 canals, 3 canals, and 4 canals 6.1%, 67.4%, and 26.5% of the time,
      respectively. The number, distribution, and apical exit of the canals were
      compared with the results of previous related reports. Several recommendations
      were given to aid in the diagnosis and treatment of extra root canals.

PMID- 9641147
TI  - Shaping ability of Mity Roto 360 degrees and Naviflex rotary nickel-titanium
      instruments in simulated root canals. Part 1.
AB  - The aim of this study was to determine the shaping ability of Mity Roto 360
      degrees and Naviflex nickel-titanium rotary instruments in simulated root canals.
      In all, 80 canals consisting of four different shapes in terms of angle and
      position of curvature were prepared by Mity Roto 360 degrees and Naviflex
      instruments using the techniques recommended by the manufacturers. This study
      describes the efficacy of the instruments in terms of preparation time,
      instrument failure, canal blockages, change in canal length, and three
      dimensional canal form. Overall, the mean preparation time for canals prepared
      using Mity instruments was 5.99 min and 5.81 min when using Naviflex instruments.
      Canal shape had no significant effect on the speed of preparation with either
      instrument. No instruments separated during the study; however, 14 Naviflex and 2
      Mity instruments were deformed. Canal type did not influence significantly the
      tendency of either instrument to deform. None of the canals became blocked with
      debris during preparation. The majority of canals prepared by both instruments
      retained their original working length, and there was no significant difference
      between the canal shapes in terms of the mean loss of distance or category of
      distance change for either instrument. Apical stops as judged from intracanal
      impressions were present in 29 (72%) of the canals prepared with Mity instruments
      and in 33 (82%) of those prepared with Naviflex instruments. However, the
      majority were judged to be of poor quality. Significant differences (p < 0.05)
      were noted in the quality of apical stops between the canal types using Mity
      instruments. Canals prepared with Mity and Naviflex instruments were found to be
      smooth in the apical half of the canal in approximately one-half of the specimens
      and coronally in nearly all canals. Neither instrument produced horizontal or
      longitudinal grooves. Favorable flow characteristics were apparent in over one
      half of the canals prepared with Mity Roto instruments; however, nearly all
      specimens had poor taper. Flow and taper were generally poor in the specimens
      prepared with Naviflex instruments. Under the conditions of this study, Mity Roto
      360 degrees and Naviflex instruments prepared canals rapidly, with no
      separations, canal blockages, and with minimal change in working length.
      Although, flow was adequate using Mity Roto 360 degrees instruments, the taper
      characteristics were less than ideal compromising the three-dimensional form of
      the canals. Naviflex instruments, while creating better taper, produced poorer
      flow characteristics. The results suggest that when using Mity Roto 360 degrees
      or Naviflex instruments, the stepdown sequence should be modified to improve
      canal flow and taper. Alternatively, an instrument with increased taper should be
      used to complete preparation before obturation.

PMID- 9641148
TI  - Shaping ability of Mity Roto 360 degrees and Naviflex rotary nickel-titanium
      instruments in simulated root canals. Part 2.
AB  - The aim of this study was to determine the shaping ability of Mity Roto 360
      degrees and Naviflex rotary nickel-titanium instruments in simulated canals.
      Forty simulated root canals made up of four different shapes in terms of angle
      and position of curvature were prepared by both sets of instruments using a
      stepdown approach. This study describes the efficacy of the instruments in terms
      of prevalence of canal aberrations, the amount and direction of canal
      transportation, and thus the overall postoperative shape. Pre- and postoperative
      images of the canals were taken using a videocamera attached to a computer with
      image analysis software. The pre- and postoperative views were superimposed to
      highlight the amount and position of material removed during preparation. Neither
      Mity Roto 360 degrees nor Naviflex instruments created any zips or elbows. Ledges
      were produced in 20 (50%) canals prepared with Mity instruments and in 29 (72%)
      canals prepared with Naviflex instruments. Statistically significant differences
      (p < 0.001) between canal shapes occurred in relation to the incidence of ledges
      with 40 degrees canals (35) associated with more aberrations than 20 degrees
      canals (14); the position of the beginning of the curve had no effect. The
      distance of ledges from the end point of preparation was also affected
      significantly (p < 0.01) by canal shape. Neither instrument created any
      perforations or danger zones. At specific positions along the canal length, canal
      shape had a significant influence on total width and the amount of material
      removed from the inner and outer aspects of the canal curve. The direction of
      canal transportation at the end point of preparation was most frequently toward
      the outer aspect of the curve in canals prepared with Naviflex instruments,
      whereas the Mity instruments produced a more balanced preparation. At the apex
      and beginning of the curve, transportation with both instruments was generally
      toward the outer aspect of the curve. Overall, mean absolute transportation was
      small and was below 0.1 mm at every position except the orifice. Under the
      conditions of this study, Mity Roto 360 degrees and Naviflex rotary instruments
      prepared canals with a high incidence of ledges. However, in the absence of other
      aberrations, both instruments would seem to be a valuable addition to the
      endodontic armamentarium.

PMID- 9641149
TI  - Herpes zoster infection as a differential diagnosis of acute pulpitis.
AB  - Many diseases can cause orofacial pain, and the diagnosis must be established
      before final treatment. This case report presents a patient with orofacial pain
      that was diagnosed as an acute pulpitis. However, there was no evidence of this
      problem on examination. After 4 days, the patient showed multiples vesicles on
      the face, and a herpes zoster viral infection was diagnosed. The patient was
      treated with acyclovir and, after 2 yr, she still complains of facial
      sensitivity.

PMID- 9641150
TI  - Osseointegration treatment of transverse root fractures in the region of the
      alveolar crest.
AB  - A method of using osseointegrated implants as an alternative treatment modality
      for transverse root fractures near the osseous crest is presented. A 15-mm
      Branemark implant was placed immediately after extraction of a maxillary central
      incisor with transverse root fracture. Five months after stage I surgery, the
      implant was uncovered. Custom fabrication of a substructure core cast directly to
      the titanium single tooth abutment was necessary due to the palatal inclination
      of the fixture. An overcasting porcelain fused to gold crown was fabricated to
      avoid an unesthetic labial access for the abutment screw. This treatment
      indicates that the use of osseointegrated implants seems to provide an effective
      solution to replacing teeth with transverse root fractures.

PMID- 9641151
TI  - Identification of a gene for nephronophthisis.

PMID- 9641152
TI  - Autosomal dominant hypertension with brachydactyly: an enigmatic form of
      monogenic hypertension.

PMID- 9641153
TI  - Cell growth and cell death in renal distal tubules, associated with diuretic
      treatment.

PMID- 9641154
TI  - Oxidative stress as the triggering event for vascular remodelling.

PMID- 9641155
TI  - Goodpasture syndrome and end-stage renal failure--to transplant or not to
      transplant?

PMID- 9641156
TI  - Why are mutations in COL4A5 not detectable in all patients with Alport's
      syndrome?

PMID- 9641157
TI  - Glomerular involvement in Behcet's disease.

PMID- 9641158
TI  - Microdomain structure of polymeric surfaces--potential for improving blood
      treatment procedures.

PMID- 9641159
TI  - Does pre-operative duplex examination improve patency rates of Brescia-Cimino
      fistulas?

PMID- 9641160
TI  - Continuous renal replacement therapies in sepsis: where are the data?

PMID- 9641161
TI  - Honesty in publication.

PMID- 9641162
TI  - Podocytes and the development of segmental glomerulosclerosis.

PMID- 9641163
TI  - Skin cancers in transplant patients.

PMID- 9641164
TI  - Laudatio for Professor Mary G. McGeown.

PMID- 9641165
TI  - Primary and secondary uraemic hyperparathyroidism: from initial clinical
      observations to recent findings.

PMID- 9641166
TI  - Molly McGeown and renal transplantation.

PMID- 9641167
TI  - Cytokine regulation of low-density lipoprotein receptor gene transcription in
      human mesangial cells.
AB  - BACKGROUND: The intracellular transport of lipids through regulation of the LDL
      receptor (LDLr) may be important in the progression of renal dysfunction. The
      present study was undertaken to investigate whether cytokines have any major
      effects on LDLr regulation and lipid-mediated glomerular injury in human
      mesangial cells (HMC). METHODS: We explored the effects of 50 ng/ml of tumour
      necrosis factor alpha (TNF alpha), 5 ng/ml of transforming growth factor beta
      (TGF beta), platelet-derived growth factor (PDGF), and interleukin-1beta (IL
      1beta) on the regulation of LDLr gene transcription in a human mesangial cell
      line (HMCL) using cell proliferation, LDL binding, northern blot and LDLr
      promoter activity assays. RESULTS: TNF alpha, TGF beta, PDGF or IL-1beta did not
      significantly stimulate HMCL proliferation at the concentrations given above, but
      maximally stimulated LDLr mRNA expression and increased LDLr promoter activity by
      167.48+/-23.56%, 150.47+/-24.41%, 127.71+/-24.65% and 163.01+/-31.91%
      respectively, at 24 h. An increased LDL binding was observed in parallel with
      increased LDLr mRNA. The tyrosine kinase transduction pathway was involved in
      LDLr upregulation induced by all four cytokines. Additionally, TGF beta involved
      serine/threonine kinase and G-protein pathways, and IL-1beta involved calmodulin,
      serine/threonine kinase and PKC pathways in upregulating LDLr. A high
      concentration of LDL (250 microg/ml) inhibited promoter activity, but TNF alpha,
      TGF beta, PDGF and IL-1beta co-incubated with LDL could override transcriptional
      inhibition by LDL. CONCLUSION: TNF alpha, TGF beta, PDGF and IL-1beta increased
      LDLr gene expression by increasing sterol-independent and mitogenesis-independent
      gene transcription. This process may contribute to lipid deposition and foam cell
      formation in HMC.

PMID- 9641168
TI  - Differentiating and proliferative effects of HGF in renal proximal tubular cells
      are mediated via different signalling pathways.
AB  - BACKGROUND: As a renotropic cytokine, hepatocyte growth factor (HGF) prevents
      acute renal failure and accelerates renal regeneration. HGF initiates its
      biological effects by interaction with specific transmembrane receptors, the c
      Met proto-oncogene, possessing an intracellular tyrosine kinase domain. We tested
      the hypothesis of whether the complex biological effects of HGF in renal proximal
      tubular cells are mediated by different intracellular signalling cascades and/or
      different receptors. METHODS: PT-1 cells, a proximal tubular cell line derived
      from rabbit kidney, were cultured under defined serum-free conditions to examine
      the biological effects of exogenously added HGF. By specific assays, we
      determined HGF binding and its effects on cell proliferation, migration,
      scattering and tubulogenic differentiation. To investigate whether HGF action
      could be inhibited by protein tyrosine kinase inhibitors (PTKIs), cells were
      incubated with HGF and different concentrations of herbimycin A, genestein,
      methyl-2,5-dihydroxycinnamate (MDC) and geldanamycin. All PTKIs are known
      inhibitors of pp60(c-src), a non-receptor tyrosine kinase involved in cell growth
      control. RESULTS: HGF bound with high affinity to cell membrane receptors and
      displayed multiple biological effects. Compared with serum-free controls, HGF
      increased the number of microvilli 1.5-fold, enhanced cell proliferation and
      migration 1.8-fold, and stimulated the formation of tubular structures 2.3-fold.
      Consistent with the known tyrosine kinase activity of the c-Met receptor, the
      mitogenic and motogenic effects of HGF were inhibited by PTKIs in a dose
      dependent manner with the following order of potency: geldanamycin > herbimycin A
      > genestein > MDC. In contrast, however, the HGF-induced tubulogenic cell
      differentiation was not inhibited specifically by PTKIs. CONCLUSIONS: The finding
      that PTKIs inhibited the mitogenic response but not the tubulogenic
      differentiation induced by HGF indicates different intracellular signal
      transduction pathways. We suggest that pp60(c-src) plays a key role in mediating
      the mitogenic and motogenic action of HGF, whereas tubulogenic cell
      differentiation induced by HGF is transduced by a pp60(c-src)-independent
      signalling pathway.

PMID- 9641169
TI  - Comparative study of cyclosporin A, cyclosporin G, and the novel cyclosporin
      derivative IMM 125 in isolated glomeruli and cultured rat mesangial cells: a
      morphometric analysis.
AB  - BACKGROUND: One adverse side-effect of the immunosuppressive drug cyclosporin A
      (CsA) is a decrease in glomerular filtration rate (GFR). This effect might be the
      result of increased glomerular contractions. The present study compared the
      contractile effects of CsA, cyclosporin G (CsG) and the novel cyclosporin
      derivative IMM 125 in isolated rat glomeruli and primary cultures of rat
      mesangial cells. METHODS: Interactive image analysis was used to measure
      glomerular and mesangial cell contraction. RESULTS: CsA, CsG, and IMM 125 at
      concentrations of 0, 10(-9), 10(-8), 10(-7), 10(-6) and 10(-5) M caused a time
      dependent and a concentration-dependent contraction of isolated glomeruli and
      mesangial cells 30 min after incubation. In glomeruli, CsA was more potent than
      CsG and IMM 125. In mesangial cells, IMM 125 also exhibited the lowest
      contractile activity, while CsA and CsG were almost equally myoreactive. The
      absolute degree of the glomerular contraction was proportional to the number of
      contracting mesangial cells in one glomeruli. The number of responding cells
      after incubation with IMM 125 and CsG were lower compared to CsA, which might
      explain the different response with CsG and CsA in both models. CONCLUSIONS:
      Since the concentrations used in these experiments were close to that reached in
      rat serum after treatment with CsA, the present results suggest that the
      contractile effects of IMM 125 and CsG in isolated glomeruli were clearly smaller
      compared to CsA, which might reflect the cyclosporins induced GFR changes in
      vivo.

PMID- 9641170
TI  - Distinct regulation of IL-8 and MCP-1 by LPS and interferon-gamma-treated human
      peritoneal macrophages.
AB  - BACKGROUND: Interleukin-8 and monocyte chemotactic protein-1 (MCP-1) are major
      leukocyte chemoattractants during bacterial peritonitis by recruiting neutrophils
      and monocytes/macrophages respectively. METHODS: Peritoneal macrophages (PM) from
      12 different CAPD patients with peritonitis were stimulated with either 10 ng/ml
      LPS, 10 ng/ml IFN-gamma or LPS+IFN-gamma, and IL-8 and MCP-1 production was
      determined on protein and mRNA levels by using ELISA technique and Northern blot
      analysis. To obtain information from two different stages of activation,
      experiments were done with highly activated PM directly after isolation and with
      cells after 10 days in culture, each group being stimulated for 4 h. Unstimulated
      cells served as control. RESULTS: Immediately after isolation IL-8 mRNA
      expression and synthesis was high and could be further increased by LPS
      stimulation, whereas IFN-gamma treatment showed no significant influence. The
      levels of MCP-1 were also initially high but could not be further stimulated by
      LPS, whereas addition of IFN-gamma resulted in a significant rise in MCP-1
      synthesis. After 10 days in culture LPS-stimulation of cells again revealed a
      significant increase in IL 8 protein synthesis, whereas IFN-gamma showed no
      effect. LPS anergy for MCP-1 was still seen in PM after 10 days in culture, and
      IFN-gamma treatment again induced a significant rise in MCP-1 synthesis. The
      overall production of both chemokines was far higher on day 1 compared to day 10.
      CONCLUSION: Our data show differences in LPS/IFN-gamma regulation for IL-8 and
      MCP-1 in both highly activated and in resting, mature peritoneal macrophages,
      suggesting distinct pathways for these chemokines that may offer a means of
      control for the specific recruitment of neutrophils and monocytes/macrophages in
      bacterial peritonitis.

PMID- 9641171
TI  - Modulation of transgene expression in mesothelial cells by activation of an
      inducible promoter.
AB  - BACKGROUND: The efficacy of peritoneal dialysis and its success as a long-term
      treatment depends on the preservation of the integrity of the peritoneal
      membrane. With increasing time on dialysis, the membrane may become compromised
      resulting in decreased dialysing capacity. We have pursued an innovative
      strategy, i.e. genetic modification of the mesothelial cell to change the
      properties of the membrane to potentially improve its dialysing capacity and
      longevity, and have demonstrated the feasibility of this approach in a rat model
      of ex vivo gene transfer. The potential to regulate transgene expression in this
      model is examined here. METHODS: Rat peritoneal mesothelial cells (MCs) were
      stably modified to express human growth hormone (hGH) under control of the heavy
      metal ion and glucocorticoid-regulatable murine metallothionein-1 promoter. The
      effect of zinc and the synthetic glucocorticoid dexamethasone on hGH expression
      was analysed in MC clones maintained in continuous passage or stationary phase,
      and in our rat model of ex vivo gene transfer. RESULTS: Exposure of these clones
      to zinc and dexamethasone, either singly or in combination, resulted in
      significant (i.e. 2-200-fold) increases in hGH production. Zinc-induced
      modulation of hGH production was demonstrated in cells in continuous passage and
      stationary culture. Regulation was also demonstrated after ex vivo gene transfer
      by both the intraperitoneal administration of zinc ions or the systemic
      administration of dexamethasone. CONCLUSIONS: Our results demonstrate the
      modulation of transgene expression in MCs in vitro and in vivo, and suggest the
      potential for the regulation of gene expression in a genetically modified
      mesothelium that may ultimately be used for the delivery of therapeutic proteins
      to maintain peritoneal membrane viability in the peritoneal dialysis patient.

PMID- 9641172
TI  - Differences between women and men with chronic renal disease.
AB  - BACKGROUND: The purpose of the present study was to compare the participation of
      women and men in the protocols of the Modification of Diet in Renal Disease
      (MDRD) study, a multicenter prospective randomized clinical trial, and to assess
      gender differences in their renal outcomes. METHODS: Of the 840 participants in
      the MDRD study, 332 (39.5%) were women who were assigned randomly to the dietary
      protein and blood pressure groups and followed for a median of 2.2 years. A
      subgroup analysis of the MDRD study database was carried out to compare women and
      men participants in recruitment, baseline characteristics, adherence to protocol
      requirements, safety and outcomes, and progression of renal disease and its
      response to dietary and blood pressure interventions. RESULTS: Adherence by women
      to the requirements of the protocol including diet, record keeping, office
      visits, glomerular filtration rate (GFR) measurements and urine collections was
      equivalent to that of men. Women had different renal diagnoses, less proteinuria
      and lower serum creatinine levels for given GFRs than men. When participants were
      grouped above and below age 52, the younger women had lower mean arterial
      pressure than did the men. Older women compared with younger had higher mean
      arterial pressure, body weight and body mass index, and total low density
      lipoprotein cholesterol. These differences were not seen between males of the
      same two age groups. During follow-up, the rate of GFR fall was slower in women,
      especially in the younger group. However, the association between gender and the
      rate of fall in GFR was attenuated and became non-significant after adjusting for
      differences in blood pressure, proteinuria and high density lipoprotein
      cholesterol. In analyses of the full cohort, there were no significant
      differences between women and men in the effects of the low protein or low blood
      pressure intervention in patients with either moderate (study A) or advanced
      (study B) renal disease. However, in subgroup analyses of patients in study A,
      there was some evidence of a lesser effect in women than in men. CONCLUSIONS:
      This exploratory analysis of the MDRD study indicates a slower mean GFR decline
      in women as compared with men. The slower mean GFR decline and suggestive
      evidence of a lesser beneficial effect of the low protein diet and low blood
      pressure interventions in women suggest that gender differences should be
      considered in trials of the effects of these interventions on the progression of
      renal disease. Also, the participation of women in the MDRD study was excellent
      and equivalent to that of men.

PMID- 9641173
TI  - Long-term outcome according to renal histological lesions in 118 patients with
      monoclonal gammopathies.
AB  - BACKGROUND: The prognosis of monoclonal gammopathies with multiple myeloma and
      renal involvement is poor, and the indication for renal replacement therapy is
      controversial. Few studies address the value of renal histology for determining
      prognosis according to initial pathology findings. METHODS: We studied the course
      of 118 patients with multiple myeloma according to renal biopsy lesions. The
      monoclonal component was identified and quantified in serum and urine. Tumor cell
      mass was classified as stage 1, 2 or 3, according to Durie and Salmon. End-points
      were death, or survival on dialysis, or serum creatinine level at last
      examination. RESULTS: Renal biopsy showed myeloma kidney in 48 cases (41%), AL
      amyloidosis in 35 (30%), light chain deposit disease in 22 (19%), chronic
      tubulointerstitial nephritis in 12 (10%) and cryoglobulinaemic kidney with
      multiple myeloma in 1. Maintenance haemodialysis was required in 46 patients
      (39%), earlier (P<0.0001) in myeloma kidney (mean: 3 months after diagnosis) than
      in AL-amyloidosis (mean: 15 months) and light chain deposit disease (mean: 18
      months). Median survival was 12 months in myeloma kidney, 24 months in AL
      amyloidosis and 48 months in light chain deposit disease. Dialysis increased
      survival in light chain deposit disease, in contrast with myeloma kidney and AL
      amyloidosis patients whose survival was shorter when dialysed. The main cause of
      death during first year of dialysis was cardiac involvement in AL-amyloidosis,
      and sepsis or cardiac insufficiency in myeloma kidney. There was a trend to
      increased survival with multidrug chemotherapy which seemed to slow progression
      to end-stage renal failure. At last follow-up (median: 12 months, range 1-297),
      65 (55%) patients had died. By multivariate analysis, independent predictors of
      survival were: age < 70, serum creatinine < or = 300 micromol/l, and serum
      calcium < or = 2.5 mmol/l. CONCLUSIONS: Initial renal biopsy helps predict
      prognosis in patients with multiple myeloma and renal involvement. Maintenance
      haemodialysis is a reasonable indication in light chain deposit disease and AL
      amyloidosis, especially in patients aged < 70. Multidrug therapy tends to prolong
      survival and slow progression to end-stage renal disease.

PMID- 9641174
TI  - Intestinal absorption and biliary secretion of cholesterol in rats with nephrotic
      syndrome.
AB  - BACKGROUND: Nephrotic syndrome (NS) results in hypercholesterolemia which is
      attributed to increased production and decreased removal of cholesterol-rich
      lipoproteins. Adjustments in intestinal absorption are reportedly involved in
      cholesterol homeostasis. We, therefore, studied the intestinal absorption and
      biliary excretion of cholesterol in NS. METHODS: We studied intestinal absorption
      (by in vivo perfusion and in vitro everted sac incubation techniques) and biliary
      secretion (by common bile duct cannulation) of cholesterol in rats with puromycin
      induced NS. The results were compared with those obtained from pair-fed control
      (PF) animals, those given free access to food (NL) or those fed a
      hypercholerolemic diet (H-chol group). Micellar solutions of Krebs' phosphate
      buffer containing trace amounts of [14C]inulin and [3H]cholesterol, as well as
      different concentrations of unlabeled cholesterol, were used for absorption
      studies. RESULTS: The NS and H-chol groups showed severe and comparable
      hypercholesterolemia. No significant difference was found in the rate of biliary
      cholesterol secretion among the study groups. Likewise, the rates of in vivo and
      in vitro cholesterol absorptions in the NS and H-chol groups were comparable with
      one another and similar to those found in the NL and PF groups. The rate of in
      vitro cholesterol absorption was directly proportional to its concentration in
      the incubation media at low concentrations. However, the absorption rate showed a
      pattern consistent with saturable transport at high cholesterol concentrations in
      all groups. CONCLUSIONS: We conclude that intestinal absorption and biliary
      secretion of cholesterol are not appreciably influenced by either nephrotic or
      diet-induced hypercholesterolemia in rats. The data further suggest that
      cholesterol absorption may be a saturable process.

PMID- 9641175
TI  - Effects of two low-flux cellulose acetate dialysers on plasma lipids and
      lipoproteins--a cross-over trial.
AB  - BACKGROUND: Studies have shown a beneficial effect of high-flux dialysis on
      lipids, lipoproteins and lipoprotein lipase (Lpl) activity. This has been
      attributed to improved clearance of Lpl-inhibitory molecules of middle molecular
      weight, but differences in flux or biocompatibility have not been addressed. We
      conducted a blinded cross-over trial of two cellulose acetate dialysers (AN140,
      Althin Medical Inc. and CA210, Baxter Inc.) of similar flux (11 ml/h/mmHg
      transmembrane pressure) but with different clearances of larger molecules [AN140
      sieving coefficient at mol. wt 11,000 Da (beta2-microglobulin) 0.6; CA210 sieving
      coefficient negligible]. METHODS: Sixteen patients were divided into two groups
      to receive dialysis with AN140 for 1 week followed by CA210 or vice versa. Before
      and after the third dialysis with each membrane, plasma lipid and lipoprotein
      concentrations were measured. Post-dialysis post-heparin lipase activity was
      measured in six patients. RESULTS: Fifteen patients completed the study. No
      difference between dialysers was found for apolipoprotein (apo) A1, B or total
      cholesterol measurements. The rise in triglyceride post-dialysis was attenuated
      by AN140 (rise 0.05 +/- 0.4 mmol/l vs CA210 0.44 +/- 0.54 mmol/l, P=0.03), while
      high density lipoprotein (HDL) cholesterol was increased by AN140 (rise 0.18 +/-
      0.12 mmol/l vs CA210 0.06 +/- 0.14 mmol/l, P<0.02). ApoE rose with AN140 during
      dialysis but declined with CA210 (1.10 +/- 1.06 mg/dl and -0.77 +/- 0.63 mg/dl,
      P=0.002) as did apoCIII (HDL) (AN140 rise 1.33 +/- 2.06 mg/dl; CA210 fall -0.67
      +/- 0.73 mg/dl, P=0.001). Lpl activity, measured in six patients, tended to be
      higher for AN140 (45.3 +/- 10.5 mmol FFA/ml plasma/h vs CA210 (37.2 +/- 7.9 mmol
      FFA/ml plasma/h) (P=0.16). CONCLUSIONS: We conclude that low-flux dialysis using
      a cellulose acetate membrane with good clearance of higher molecular weight
      molecules may be associated with beneficial changes in plasma lipids and
      lipoproteins.

PMID- 9641176
TI  - Removal of cytokines and activated complement components in an experimental model
      of continuous plasma filtration coupled with sorbent adsorption.
AB  - BACKGROUND: Sepsis is associated with enhanced cytokine production. Here, we
      examined the in vitro removal of plasma cytokines during continuous
      plasmafiltration coupled with sorbent adsorption. METHODS: Proinflammatory
      (tumour necrosis factor-alpha, interleukins-1, -8) and anti-inflammatory
      (interleukin 1 receptor antagonist, soluble tumour necrosis factor receptor type
      I and II) cytokines in whole blood spiked with Escherichia coli endotoxin were
      determined during 2-h recirculation in the ultrafiltrate (condition A), plasma
      filtrate (condition B), before and after different sorbents (of the Amberlite-,
      Amberchrome- Ambersorb -type and charcoal). We studied the maximal adsorbing
      capacity, the 1% leakage test for cytokines and C3a des Arg and the adsorption of
      complement-dependent leukocyte chemiluminescence. Plasma proteins eluted from the
      resins were examined by sodium dodecyl sulphate polyacrylamide gel
      electrophoresis and immunoblotting with an anti-human alpha2-macroglobulin.
      RESULTS: In condition B, we observed a 40- and 121-fold % increase (vs condition
      A) in the removed mass and clearance of tumour necrosis factor-alpha. For all
      other cytokines, the removed mass and the clearance increased from 2.3- up to 6
      fold. The Amberchrome but not the Amberlite or Ambersorb resins could remove the
      highest amount of cytokines and could reduce complement-dependent
      chemiluminescence. Two protein bands of approximately 400,000 D and 200,000 D
      were eluted only from Amberchrome resins and immunoprecipitated by anti-human
      alpha2-macroglobulin and anti-human C3c antibodies, respectively. CONCLUSIONS:
      These studies suggest an efficient removal of cytokines in continuous
      plasmafiltration with sorbent adsorption. The binding of alpha2-macroglobulin, a
      carrier of cytokines in plasma, might be a additional mechanism in the removal of
      cytokines from plasma.

PMID- 9641177
TI  - Alterations of synovial tissue and their potential role in the deposition of
      beta2-microglobulin-associated amyloid.
AB  - BACKGROUND: Beta-2-microglobulin-associated amyloidosis (AB2M) is a frequent
      complication of long-term dialysis treatment. Uraemic retention of beta2
      microglobulin (beta2M) apparently constitutes the basis for AB2M. However, it is
      unclear why clinical manifestations are largely confined to osteoarticular
      tissues. It has been speculated that synovial inflammatory changes, induced by
      uraemia and/or dialysis therapy could predispose this tissue to amyloid
      deposition. METHODS: We investigated which local synovial alterations preceded or
      paralleled amyloid deposition. Using immunohistology we evaluated synovial
      leukocyte infiltration (B and T lymphocytes, monocytes/macrophages), cell
      proliferation, fibroblast activation (de novo expression of alpha-smooth-muscle
      actin), the expression of extracellular matrix components (heparan sulphate
      proteoglycan, collagen types I, III, IV), and advanced glycation end-products
      (AGEs). RESULTS: Synovial AB2M was detected in 20 of 36 chronic peritoneal and
      haemodialysis patients and none of eight non-uraemic controls. Notably, non-AB2M
      synovial amyloid was present in six additional dialysis and three control
      patients. Cellular infiltration was largely restricted to patients with advanced
      AB2M deposits. The infiltrates consisted mainly of macrophages and progressed
      with increasing degrees of AB2M deposition. In advanced cases they exhibited
      characteristics of a foreign-body reaction. Other infiltrating leukocyte types,
      altered cell proliferation, or fibroblast activation were absent or uncommon in
      periarticular tissue of dialysis patients with and without AB2M. Neither dialysis
      treatment nor the presence of AB2M deposits appreciably altered the qualitative
      matrix composition in periarticular tissue. AGEs were present in AB2M deposits,
      the extracellular synovial matrix of dialysis patients (of both, patients with
      and without AB2M) and, to a lesser degree, in synovia of controls. CONCLUSIONS:
      These data suggest that, except for AGE formation, alterations of none of the
      parameters assessed, and in particular no inflammatory tissue alterations,
      precede periarticular AB2M. Rather synovial tissue, possibly modified by AGEs,
      seems to have an intrinsic propensity for amyloid deposition and inflammatory
      changes appear to only arise secondary to amyloid deposition.

PMID- 9641178
TI  - Anorexigen (TNF-alpha, cholecystokinin) and orexigen (neuropeptide Y) plasma
      levels in peritoneal dialysis (PD) patients: their relationship with nutritional
      parameters.
AB  - BACKGROUND: Malnutrition has definitely been related to mortality among dialysis
      patients. Persistent loss of appetite is one of the major symptoms found in these
      patients. It is also well recognized that several substances produce anorexia or
      disorders of the hunger-satiety cycle in several diseases. The aim of this study
      was to identify the role of anorexigen substances (TNF-alpha and cholecystokinin
      or CCK) and an orexigen substance (neuropeptide Y or NPY) in anorexia and
      malnutrition among 55 clinically stable peritoneal dialysis (PD) patients.
      RESULTS: High TNF-alpha plasma levels were found in 41 of 42 patients (97.6%)
      with a mean of 70.5+/-32.3 pg/ml. Patients with anorexia (n=11) or anorexia with
      nausea or vomiting (n=5) had higher TNF-alpha values than patients without these
      symptoms (75.9+/-34 vs 52.1 +/-24.5 pg/ml, P<0.05). Eight patients with a prior
      diagnosis of acid pylori disease showed higher TNF-alpha values (87.2+/-24.3)
      than 30 unaffected patients (63.6+/-30.5, P<0.05). TNF-alpha showed a significant
      negative linear correlation with retinol binding protein (RBP) (r=-0.37, n=34,
      P<0.05), and venous pH (r=-0.4, n=42, P<0.01); also, TNF-alpha values higher than
      65 pg/ml were inversely associated with transferrin, cholesterol, blood urea
      nitrogen (BUN) and CCK. Patients with prealbumin levels lower than 30 mg/dl, a
      BMI lower than 30 kg/m2, nPCR lower than 1.1 g/kg/day and urea KT/V lower than
      2.2 showed higher serum TNF-alpha levels. Patients who had been on CAPD treatment
      for longer periods showed higher TNF-alpha values. High plasma CCK levels were
      found in 38 of 45 patients (84%), mean 45.9+/-32.3 pg/ml. Patients with anorexia
      had no difference in CCK values compared with those without. A direct association
      was found between CCK levels and some nutritional markers (albumin, fibronectin,
      triglycerides, folic acid and nPCR in non diabetic patients). Although CCK has a
      recognized anorectic effect, this direct association might be because of an
      abnormal stimulation of CCK glucose feedback (trypsin) due to continuous
      peritoneal glucose absorption. This suggests that CCK could be an immediate food
      intake marker in PD patients. The NPY plasma levels were normal in 33 patients,
      high in 6 and low in 11. Patients with anorexia showed lower NPY levels than
      those without. NPY values greater than 50 pg/ml were directly associated with
      higher transferrin, prealbumin, RBP, nPCR and urea KT/V values. Importantly, a
      negative linear correlation between NPY and TNF-alpha was found (r=-0.42, n= 41,
      P<0.01). There was no significant relationship between residual renal clearance
      and the serum levels of the three peptides. CONCLUSION: In conclusion, our data
      suggest that high TNF-alpha and low NPY serum levels are associated with
      anorexia. High TNF-alpha, low CCK and low NPY serum levels are also related to a
      poor nutritional status. Further research on these circulating substances is
      required.

PMID- 9641179
TI  - Nutritional assessment of children on haemodialysis: value of IGF-I, TNF-alpha
      and IL-1beta.
AB  - BACKGROUND: Protein-energy malnutrition (PEM) is associated with increased
      morbidity and mortality in haemodialysis (HD) patients. Insulin-like growth
      factor I (IGF-I) has proved to be a sensitive marker of malnutrition, while
      interleukin-1 (IL-1beta) and tumour necrosis factor (TNF) have been found to be
      raised in catabolic states. METHODS: We have investigated the nutritional status
      of 17 chronic renal failure (CRF) paediatric patients (8 boys, 9 girls) on
      maintenance HD. Eight predialysis CRF children (5 boys and 3 girls; mean
      creatinine 5.1+/-3.2 mg/dl) and 10 healthy children served as control groups. PEM
      was defined according to anthropometric measurements (triceps skinfold thickness
      (TST), mid-arm circumference (MAC), and mid-arm muscle circumference (MAMC)).
      These were correlated with serum IGF-I, IL-1, TNF-alpha, transferrin, and albumin
      (all sampled before the HD session). RESULTS: In the HD group, TST was reduced in
      41.2% of the patients, whereas MAC and MAMC were reduced in 82.4 and 76.5%
      respectively. TST was depleted in only one of the predialysis CRF children. The
      degree of reduction in MAC and MAMC were 62.5 and 62.5% respectively. Median
      serum IGF-I level was decreased in both HD and predialysis CRF patients (205.1
      interquartile range (IQR) 194.4 microg/l and 258.8 IQR 155.0 microg/l
      respectively) compared to the healthy children (418.0 IQR 310.5 microg/l)
      (P=0.0009 and P=0.01 respectively). Within the HD group, IGF-I levels were lower
      in patients with malnutrition defined according to TST (145.0 IQR 125.5 microg/l)
      compared to children with normal TST (301.2 IQR 218.8 microg/l) (P=0.05). IGF-I
      levels of the HD patients with malnutrition according to TST was also lower than
      the predialysis CRF patients and healthy children (P=0.04 and P=0.002
      respectively). Serum IL-1beta was undetectable in all groups. Median serum TNF
      alpha levels were higher in HD and predialysis CRF patients compared to healthy
      children, albeit statistically insignificant. There was no correlation between
      TNF-alpha, transferrin or albumin and anthropometric parameters. CONCLUSIONS: Our
      results support the high prevalence of malnutrition in CRF children, which
      becomes more pronounced when treatment by HD is initiated. We suggest that
      determination of IGF-I levels in childhood HD patients in conjunction with
      anthropometric measurements is useful for identification of malnutrition. We have
      not been able to demonstrate the catabolic effects of cytokines on this state of
      protein energy malnutrition.

PMID- 9641180
TI  - Regression of left ventricular hypertrophy in haemodialysis patients by
      ultrafiltration and reduced salt intake without antihypertensive drugs.
AB  - BACKGROUND: Left ventricular hypertrophy (LVH) is very frequent in haemodialysis
      patients. Only few investigations have reported its regression, and only by the
      use of antihypertensive drugs. Because volume load is at least as important as
      pressure load, we investigated whether persistent strict volume control by
      ultrafiltration alone may be effective in improving LVH METHODS: Using blood
      pressure (BP) and cardiac dimensions as a guide, we treated all hypertensive
      patients in our dialysis unit during the 3 times weekly dialysis sessions for 4 h
      per session with as much ultrafiltration as they could stand. If they gained too
      much weight an extra isolated ultrafiltration (UF) session was applied. Special
      attention was given to dietary salt restriction. The study group of all 15
      patients in whom echocardiographic assessment had been made at least 1.5 years
      previously was selected retrospectively, and we acknowledge that important
      confounding factors might not have been controlled for. Cardiothoracic index
      (CTI) was estimated on the chest X-ray. Diameters of left atrium (LA), left
      ventricle systolic (LVS) and diastolic (LVD), interventricular septum (IVS),
      posterior wall (PW), and left ventricular mass index (LVMI) were estimated by
      standard echocardiographic methods. RESULTS: Mean arterial pressure of the study
      group had been lowered by UF before the first echocardiogram from predialysis
      136+/-11 to 101+/-14 and from postdialysis 119+/-8 to 92+/-12 mmHg. During a mean
      follow-up period of 37+/-11 months LVMI decreased from 175+/-60 to 105+/-11 g/m2.
      CTI decreased further from 48+/-3 to 43+/-4%, while significant decreases of LA
      (22.5+/-3 to 19.9+/-4 mm/m2), LVS (18.7+/-4 to 15.9+/-3 mm/m2) and LVD (28.3+/-4
      to 24.0+/-3 mm/m2) were seen in all patients. There also was a further decrease
      in both pre- and postdialysis BP to 116+/-12/73+/-7 and 105+/-7/65+/-3 mmHg
      respectively. CONCLUSION: The results of this uncontrolled retrospective study
      suggest that good long-term BP control and a decrease of LVM can be achieved by
      continuous efforts to control hypervolaemia. The decrease in volume may be even
      more important than pressure reduction to achieve this goal.

PMID- 9641181
TI  - Role of the donor in post-transplant renal function.
AB  - BACKGROUND: The donor, i.e. adult or paediatric, might influence the outcome of
      the graft function. METHODS: The glomerular filtration rate (GFR) of 120
      transplanted children (47 girls) aged 10.4+/-4.6 years (0.7-17.2) was
      prospectively assessed over a 5-year period. The patients were divided into two
      groups according to the age of donor: adult (donor age > 18 years; n=33) and
      paediatric (donor age < 18 years; n=87). GFR was assessed by inulin clearance at
      3, 6 and 12 months and yearly thereafter. RESULTS: The average GFR was stable in
      the range of 70 ml/min/1.73 m2 for the whole follow-up period. The adjusted GFR
      in adult graft recipients was significantly higher at 3 months post
      transplantation: 80.6+/-36.9 vs 65.1+/-22.0, P=0.02. However, from the second
      year post-transplantation, the adjusted GFR in paediatric graft recipients became
      significantly higher than that of adult graft recipients. Such results could be
      due to an improvement in the absolute GFR (ml/min) of paediatric graft recipients
      with time (P=0.0001) whereas that of the adult graft recipients remained stable
      despite the children's growth. CONCLUSIONS: The adjusted GFR of adult graft
      recipients was significantly higher than that of paediatric graft recipients in
      the early post-transplant period. In the long-term, a progressive decrease in
      adjusted GFR was noted in adult graft recipients. On the one hand, this may be
      due to a functional adaptation and/or inadequate compensatory growth of the
      graft. On the other hand, the absolute GFR of paediatric graft recipients
      increased, suggesting an ongoing capacity for growth and/or compensatory
      hypertrophy after child-to-child renal transplantation.

PMID- 9641182
TI  - Pre-operative echocardiographic abnormalities and adverse outcome following renal
      transplantation.
AB  - BACKGROUND: Premature cardiovascular disease is now the leading cause of death in
      renal transplant recipients. Although patients with progressive renal disease
      have many of the conventional risk factors for cardiovascular disease these do
      not have the same predictive power as they do in the general population.
      Echocardiographic abnormalities, notably left ventricular hypertrophy, have been
      shown to be associated with adverse outcome in patients on dialysis. METHODS: The
      echocardiograms were studied from 141 patients who were examined on the eve of
      renal transplantation between 1988 and 1990 to try to identify factors predicting
      outcome. Thirty-four patients have since died, 22 of cardiovascular disease.
      Ninety-three of the survivors and 27 of the dead patients had echocardiographic
      traces suitable for analysis. RESULTS: Left ventricular mass index was increased
      in those patients who died (median 167 vs 134 g/m2; P=0.03), as were end-systolic
      (4.3 vs 3.4 cm; P<0.01) and end-diastolic (5.8 vs 5.2 cm; P<0.01) diameters.
      Systolic function was also more severely impaired (fractional shortening, 27 vs
      33%; P<0.01). Apart from age, only systolic function and end systolic diameter
      were independent predictors of outcome in multivariate analysis. CONCLUSIONS:
      This pattern of echocardiographic abnormality is similar to that reported in long
      term dialysis populations, despite the adverse effects on survival. Moreover,
      despite potential benefits of transplantation on cardiac function, left
      ventricular hypertrophy, ventricular dilatation and systolic dysfunction were all
      associated with adverse outcome following transplantation. We conclude that
      echocardiography identifies markers for premature death following transplantation
      and provides targets for therapeutic intervention.

PMID- 9641183
TI  - Renal transplantation in the management of bilateral Wilms' tumour (BWT) and of
      Denys-Drash syndrome (DDS).
AB  - BACKGROUND: Wilms' tumour (WT) occurs bilaterally in approximately 5-7% of
      affected children. In some patients, complete surgical removal of the malignant
      tissue cannot be achieved without bilateral total nephrectomy. In Denys-Drash
      syndrome (DDS), bilateral nephrectomy is indicated both because of the associated
      nephropathy usually progressing rapidly to end-stage renal failure and because of
      the high risk of WT development in any residual renal tissue. METHODS: Case
      records of patients with a diagnosis of either bilateral WT (BWT) or DDS, who
      underwent bilateral nephrectomy and subsequent renal transplantation between 1980
      and 1996 at the Hospital for Sick Children, London, were reviewed. RESULTS:
      Allogeneic renal transplantation was performed in two children with BWT and four
      with DDS, three of whom had developed unilateral WT by the time their kidneys
      were removed. Renal transplantation was performed 15-49 months after bilateral
      nephrectomy at a mean age of 45 (26-76) months, with a minimum of 1 year tumour
      free survival after completion of chemotherapy in those with WT. One patient died
      after renal transplantation. Five children had a favourable outcome, with a mean
      follow-up of 80 (29-121) months post-renal transplantation. CONCLUSION: Advances
      in dialysis and transplantation programmes for young children offer the potential
      for a marked improvement in the prognosis for patients with BWT and for those
      with DDS.

PMID- 9641184
TI  - Body composition in patients treated with peritoneal dialysis.
AB  - BACKGROUND: Malnutrition is a common complication in uremia and during
      maintenance dialysis. Several factors contribute to its development. Different
      modes of dialysis treatment may differ in their effects on nutritional status.
      METHODS: In order to analyse the nutritional consequences of peritoneal dialysis
      (PD), body composition analyses were performed in PD patients between February
      1993 and March 1996. Body cell mass (BCM) was estimated from measurements of
      total body potassium (TBK) in a whole-body counter. Total body water (TBW) was
      determined by measurement of tritiated water. Body fat (BF) was calculated from
      body weight (BW), TBK and TBW. Observed values were related to predicted (o/p)
      derived from local population studies. RESULTS: Sixty patients were repeatedly
      investigated during the study period. Of these, 34 were investigated during the
      first year of PD. At the start of dialysis, TBK o/p was 0.94 and BF o/p 0.76. No
      change in body composition was seen during the observation period in the group as
      a whole. However, within the group individual changes in BW were strongly
      correlated with individual changes in BF (r=0.66, P=0.0001). Twenty-six patients
      were examined during the second and third year of PD. In this group, BW o/p
      remained constant over time. However, there was a small but significant decline
      of TBK o/p and a concomitant increase of BF o/p (P<0.05). No correlation was
      observed between changes in TBK and changes in serum albumin. CONCLUSIONS: The
      results of this study indicate, that there may be a risk for further reduction of
      body cell mass during long-term PD treatment, while body energy stores are
      maintained or even increased.

PMID- 9641185
TI  - Use of the Valsalva manoeuvre to identify haemodialysis patients at risk of
      congestive heart failure.
AB  - BACKGROUND: In the presence of elevated cardiac filling pressures, the decline of
      blood pressure (BP) during the straining phase of a Valsalva manoeuvre is blunted
      or absent. We compared the use of non-invasively measured BP response to a
      Valsalva manoeuvre with clinical assessment and bioimpedance measurements to
      identify haemodialysis patients at risk of acute congestive heart failure (CHF).
      METHODS: Continuous BP response (Finapres) to a Valsalva manoeuvre, clinical
      assessment by nephrologists, and bioimpedance estimations of extracellular fluid
      volume were determined before and after haemodialysis, once every week during a 5
      week period. Acute CHF was defined according to preset clinical and radiological
      criteria. RESULTS: Participants (age 60+/-19 years, six females, nine males) had
      an average predialysis weight of 66.8+/-11.8 kg. Patients were dialysed for 3.8+/
      0.8 h with a mean ultrafiltration of 2.4+/-1.1 litres. Valsalva systolic BP
      ratios (phase 2 to 1) decreased significantly during dialysis from 0.81+/-0.11 to
      0.73+/-0.10 (P<0.05). Five patients experienced an episode of acute CHF. The
      Valsalva BP ratios for these patients before and after dialysis (0.89+/-0.05 and
      0.78+/-0.05 respectively) were higher than for the remaining ten patients (0.77+/
      0.10 and 0.70+/-0.11, respectively) (P<0.05). A cutoff Valsalva BP ratio of 0.82
      resulted in positive and negative predictive values for CHF of 62 and 100%
      respectively. No differences in clinical assessment or bioimpedance parameters
      were found, with the exception of postdialysis diastolic BP and predialysis ankle
      oedema. After treatment of CHF, Valsalva BP ratios decreased significantly
      without changes in the other hydration parameters. CONCLUSIONS: Non-invasive
      assessment of the BP response to a Valsalva manoeuvre appears to be a potential
      tool for identifying patients at risk of acute CHF during maintenance
      haemodialysis.

PMID- 9641186
TI  - Adding plasmapheresis to corticosteroids and alkylating agents: does it benefit
      patients with focal segmental glomerulosclerosis?
AB  - DESIGN: Eleven adult patients with biopsy-proven primary FSGS and nephrotic
      syndrome resistant to steroids and cytotoxic drugs were treated with
      plasmapheresis in addition to oral prednisolone and intravenous cyclophosphamide.
      On the average each patient had undergone 17 sessions over a period of 15-25
      weeks (mean 21.90+/-2.71 weeks). RESULTS: One month after the last plasmapheresis
      session, 72.7% (n=8) of the patients were in clinical remission of nephrotic
      syndrome in association with the stabilization of renal function. In contrast,
      patients who did not respond 27.3% (n=3) had a gradual decline in renal function.
      After a mean follow-up of 27.45+/-6.31 months, six patients who responded (54.5%)
      remained in sustained complete or partial remission of proteinuria with stable
      renal function. The mean proteinuria at the latest examination was 0.9+/-0.01 g
      per day in these patients. CONCLUSION: It is concluded that a combination of
      plasmapheresis, corticosteroids, and cyclophosphamide may obtain sustained
      improvement of proteinuria and stabilization of plasma creatinine in about half
      of the patients who proved to be refractory to therapy.

PMID- 9641187
TI  - The effect of recombinant human growth hormone treatment on bone and mineral
      metabolism in haemodialysis patients.
AB  - BACKGROUND: Uraemia and chronical haemodialysis are associated with an abnormal
      growth hormone (GH)-insulin-like growth factor (IGF) axis which may contribute to
      malnutrition and renal bone disease. Short-term studies have shown a beneficial
      effect of treatment with recombinant human growth hormone (rhGH) on nutritional
      status in patients on haemodialysis. In the present study, we evaluated the
      effect of rhGH on bone and mineral metabolism. METHODS: Twenty chronic
      malnourished patients on haemodialysis took part in a double-blind, placebo
      controlled trial with subcutaneous injections of rhGH (4 IU/m2/day) or placebo
      for 6 months. RESULTS: During rhGH treatment, serum IGF-1 increased 264 +/- 52%
      (mean +/- SEM) (P < 0.008). There were no significant changes in biochemical
      markers of mineral metabolism (serum ionized calcium, phosphate and parathyroid
      hormone). Among markers of bone metabolism, there was a significant increase in
      serum procollagen type I C-terminal propeptide (maximum 155 +/- 8%, P < 0.001)
      and no significant changes in serum alkaline phosphatase. Bone densitometry
      showed a significant decrease in whole body bone mineral content (95.7 +/- 1.2%)
      after 6 months treatment. The effects on the proximal femur were not significant.
      CONCLUSION: The effects of 6 months treatment with rhGH seen in this study are
      best explained by a GH- or IGF-1-induced increased bone turnover. Long-term
      treatment in larger cohorts followed by bone densitometry and, preferentially,
      bone histomorphometry are needed to evaluate whether this is a beneficial effect
      in haemodialysis patients.

PMID- 9641188
TI  - Removal of morphine with the new high-efficiency and high-flux membranes during
      haemofiltration and haemodialfiltration.
AB  - We present three critically ill patients with severe renal failure who required
      haemofiltration or haemodiafiltration, with high-efficiency or high-flux
      membranes, while receiving an intravenous infusion of morphine. We show that
      despite the very high ultrafiltrability/diffusability of free morphine, only 1-3%
      of the total amount of infused morphine is removed in 24 h. This is in marked
      contrast to haemodialysis where, owing to much higher dialysate flow rate, a
      significant quantity of free morphine is removed.

PMID- 9641189
TI  - Ultrafiltrable aluminium after very low doses of desferrioxamine.
AB  - BACKGROUND: The recommended dose of desferrioxamine for the treatment of
      aluminium intoxication is 5 mg/kg/week. However, there are no data about the
      efficiency of lower doses. The objective of this study was to investigate the
      capacity of very low doses of desferrioxamine in the generation of ultrafiltrable
      aluminium. METHODS: Five patients undergoing haemodialysis with a similar
      biochemical profile and serum aluminium levels >40 microg/l were studied. The
      three different doses of desferrioxamine used (0.5, 2.5 and 5.0 mg/kg) were
      administered randomly to each patient at 1 week intervals. Total and
      ultrafiltrable serum aluminium was measured before and 44 h after the
      administration of desferrioxamine. RESULTS: All doses of desferrioxamine
      significantly increased the total serum aluminium; no differences were found
      between 2.5 and 5.0 mg/kg. The total serum aluminium levels doubled with the 2.5
      and 5.0 mg/kg doses, while the increase with 0.5 mg/kg was lower (32.6%, P<0.05).
      Ultrafiltrable aluminium increased with the three doses; from 7.1+/-2.8, 3.9+/
      0.6 and 7.5+/-4.1 to 25.7+/-7.3, 44.3+/-10.1 and 59.1+/-19.8 microg/l,
      respectively (P<0.05). The efficiency of each dose was calculated using the ratio
      between the increase in ultrafiltrable aluminium and the dose of desferrioxamine
      administered. The efficiency ranged from 10.3+/-3.9 for the higher dose (5 mg/kg)
      to 37.2+/-10.3 for the lower dose (0.5 mg/kg). CONCLUSIONS: Our results suggest
      that very low-dose desferrioxamine (>5 mg/kg) increases the ultrafiltrable
      (potentially dialysable) aluminium.

PMID- 9641190
TI  - PCR diagnosis on formalin-fixed, paraffin-embedded tissues with acid-fast stain
      and culture negativity in chronic dialysis patients of cervico-mediastinal
      tuberculous lymphadenitis.
AB  - BACKGROUND: Bacteriologic studies often provide negative results in tuberculous
      infection, and do not favour early diagnosis. Polymerase chain reaction (PCR) is
      known to diagnose tuberculosis quickly. With this in mind, we used PCR to detect
      mycobacterial DNA on formalin-fixed, paraffin-embedded tissues with acid-fast
      stain and culture negativity in two dialysis patients with cervico-mediastinal
      lymphadenopathy. METHODS: Sections of neck lymph nodes were cut at two different
      levels. At each level, two semi-adjacent sections with a thickness of 5 microm
      each were cut using standard microtomes with disposable blades. The first section
      mounted on a glass slide was stained by Ziehl-Neelsen, and the second section was
      examined by PCR based on a 123 bp fragment of IS6110 that is specific for the
      Mycobacterium tuberculosis complex. RESULTS: The histology of lymph nodes
      disclosed inflammatory necrotizing granulomas, but acid-fast stain for M.
      tuberculosis was negative in the two patients. DNA of M. tuberculosis was
      detected in lymph node samples from each patient by PCR on the IS6110 element and
      by dot-blot hybridization. CONCLUSIONS: PCR assay is a potentially useful
      approach for early and rapid diagnosis of tuberculous lymphadenitis in chronic
      dialysis patients, since mycobacterial staining and culture often provide
      negative results.

PMID- 9641191
TI  - Ifosfamide-induced renal Fanconi syndrome with associated nephrogenic diabetes
      insipidus in an adult patient.

PMID- 9641192
TI  - Reversible renal failure due to specific infiltration of the kidney in chronic
      lymphocytic leukaemia.

PMID- 9641193
TI  - Disseminated intravascular coagulation complicating polyarteritis nodosa in alpha
      1-antitrypsin deficiency.

PMID- 9641194
TI  - Antimyeloperoxidase-antibody-positive rapidly progressive glomerulonephritis
      associated with Castleman's disease.

PMID- 9641195
TI  - Reversal of osteomyelosclerosis-associated systemic lupus nephritis.

PMID- 9641196
TI  - Renal artery stenosis and focal segmental glomerulosclerosis in the contralateral
      kidney.

PMID- 9641197
TI  - Gemella morbillorum--spondylodiscitis in a patient with a renal graft.

PMID- 9641198
TI  - Successful kidney retransplantation after combined liver/kidney transplantation
      in primary hyperoxaluria type I.

PMID- 9641199
TI  - Fatal hepatitis B virus infection with fibrosing cholestatic hepatitis following
      renal transplantation.

PMID- 9641200
TI  - Hepatitis-B-virus-related fibrosing cholestatic hepatitis after renal
      transplantation with acute graft failure following interferon-alpha therapy.

PMID- 9641201
TI  - Transplant renal artery aneurysm following venous patch repair of a traction
      injury to the renal artery.

PMID- 9641202
TI  - An unusual cause of pink urine.

PMID- 9641203
TI  - Acute acid-base disorder during plasma immunoadsorption treatment using citrate
      anticoagulation.

PMID- 9641204
TI  - Intravascular ultrasound to establish the indication for renal angioplasty.

PMID- 9641205
TI  - The normoglycaemic patient with nephrotic syndrome.

PMID- 9641206
TI  - Malarial nephropathies.

PMID- 9641207
TI  - Dialysis fluid composition and quality--professional opinion vs scientific
      evidence.

PMID- 9641208
TI  - Increased platelet thromboxane release in focal segmental glomerulosclerosis.

PMID- 9641209
TI  - Failure of cyclosporine A in controlling Schoenlein-Henoch purpura.

PMID- 9641210
TI  - Percutaneous drainage by multiple and bilateral puncture of infected renal cysts
      in autosomal dominant polycystic kidney disease.

PMID- 9641211
TI  - Chronic renal failure and end-stage renal disease in St Petersburg, Russia.

PMID- 9641212
TI  - Recurrent Kaposi's sarcoma in a renal transplant recipient maintained on minimum
      doses of immunosuppression.

PMID- 9641213
TI  - Sterile leukocyturia as a manifestation of urinary tuberculosis in renal
      transplant patients.

PMID- 9641214
TI  - The clinical value of digene hybrid capture HPV DNA testing in a referral-based
      population with abnormal pap smears.
AB  - PURPOSE OF INVESTIGATION: The hybrid capture human papillomavirus (HPV) DNA assay
      is offered by the manufacturer to assist clinicians with patients with ASCUS pap
      smear results to assess the risk factor and to potentially direct follow-up of
      these patients. In our practice, a gynecologic oncology practice that has a
      referral based population with abnormal pap smears, our purpose was to evaluate
      the patients referred with all grades of abnormal cervical cytology. METHODS: One
      hundred consecutive patients who were referred for evaluation of abnormal
      cervical cytology: atypical squamous cells of undetermined significance (ASCUS);
      low-grade squamous intraepithelial lesion (LGSIL); high-grade squamous
      intraepithelial lesion (HGSIL); or squamous cell carcinoma (SCC) were evaluated
      by repeat pap smear, hybrid capture HPV DNA analysis and colposcopy. Colposcopic
      findings were recorded, and if appropriate, cervical biopsies were performed.
      Hybrid capture results were correlated with histologic and cytologic findings.
      Using histopathologic diagnosis as the reference standard, the sensitivity and
      positive predictive value of pap smear and high risk HPV were calculated. The
      Kappa test was used to correlate colposcopic and histopathologic findings.
      RESULTS: Repeat pap smears at the time of initial consultation demonstrated 25
      patients with normal results, 39 with LGSIL, 30 with HGSIL, 1 SCC and 5 ASCUS.
      Seventy-eight patients underwent cervical biopsy. Colposcopic findings correlated
      significantly with histopathologic findings (p<0.0001). Forty-four percent of
      patients tested positive for HPV DNA: 40 patients with high risk HPV, three
      patients with low risk HPV, and one patient with both high risk and low risk HPV.
      Sixteen of 39 patients (41%) with LGSIL on pap smear tested positive for high
      risk HPV; 37% of patients in this group required cervical conization because
      cervical biopsies demonstrated moderate/severe dysplasia. The diagnosis of
      moderate/severe dysplasia significantly correlated with the presence of high risk
      HPV [OR 78.9 (8.31-389.30)]. There was no significant correlation between the HPV
      DNA signal strengths and the histologic grade of dysplasia. The sensitivity and
      the positive predictive value of pap smear alone in identifying moderate/severe
      dysplasia was 62% and 96%, respectively. The combination of HGSIL pap smears and
      high risk HPV increased the sensitivity but not the positive predictive value for
      the detection of moderate/severe dysplasia to 77.7% and 95%, respectively (P=NS).
      CONCLUSIONS: Although in this setting, the use of hybrid capture DNA testing did
      not significantly improve the sensitivity or positive predictive value of the
      diagnosis of HGSIL cytology when compared to cytologically indicated plus
      colposcopically directed cervical biopsies in this population of women at high
      risk for the presence of disease, the combination of HGSIL pap smears and high
      risk HPV did result in a clinically important increase in the diagnosis of
      moderate/severe dysplasia.

PMID- 9641216
TI  - Radical abdominal hysterectomy using the ENDO-GIA stapler: report of 150 cases
      and literature review.
AB  - Over a seven-year period from 1990-1997 150 consecutive patients underwent Type
      III radical abdominal hysterectomy using the ENDO-GIA stapler on the cardinal and
      uterosacral ligaments. Compared to prior patients operated on with standard
      suturing methods, the stapler patients had shorter operating times, lower blood
      loss and infection rates, and shorter hospital stays without any increase in
      recurrence rate. The equipment failure rate was 3%. Although not all improvements
      in surgical and post-operative morbidity are likely due to use of the ENDO-GIA
      stapler, the use of the stapler clearly lowered operating times, blood loss,
      surgical morbidity, hospital stay with no adverse effect on patient survival.

PMID- 9641215
TI  - Predictors of co-incidental CIN II/III amongst a cohort of women with CIN I
      detected by a screening Pap test.
AB  - Approximately 20-40% of lesions interpreted by a screening Pap test as CIN I and
      subsequently examined by colposcopy include a co-incidental CIN II/III. Since the
      HPV profiles of CIN I and CIN II/III differ, HPV typing may predict these co
      incidental higher grade lesions. Based on both the colposcopic impression and
      repeat Pap test, 537 women referred for examination of CIN I as classified by a
      screening Pap test were triaged into group A (</= CIN I) or group B (>/= CIN II).
      Clinical, demographic, reproductive, and risk factor data was collected by
      questionnaire and HPV typing of cervical scrapes was done by PCR. Group A
      included 342 (63.7%) women and group B 195 (36.3%). Group B women more frequently
      were current cigarette smokers (p<0.001) and had a high school or lesser level of
      education (p=0.04). HPV positivity amongst younger group B women (</= 21 years)
      and a history of current/occasional cigarette smoking in those 22 years and older
      were significant predictors of triaged, co-incidental CIN II/III (p<0.001). This
      age restriction will limit the adoption of HPV testing as an universal,
      adjunctive test for the identification of CIN II/III amongst CIN I lesions
      detected by a screening Pap test. A greater health advantage may be gained by
      increasing women's awareness of the risks, including that of cervical cancer
      associated with cigarette smoking.

PMID- 9641217
TI  - The size of a micrometastasis in the axilla in breast cancer: a study of nodal
      tumour-load related to prognosis.
AB  - Much has been written on micrometastases to the axilla in breast cancer but there
      is no consensus as to their size. In this study three levels of nodal tumour-load
      are defined following measurement of nodal tumour area on histology. The two cut
      points described are both of clinical interest. The smallest deposits, up to
      0.0001 cm2, include embolic growth on the afferent side of the node, which is, as
      reported previously, of poor prognosis. In such cases post-operative prognosis
      approaches that in the "node-positive", here defined as cases with an axillary
      tumour-load of 0.5 cm2 or more. Between these two groups is a collection of
      cases, 40% of the total series, with a prognosis similar to the node-negative. It
      is suggested that the deposits in this intermediate group should be termed
      micrometastases, the high risk cases with embolic growth reported as such and
      those with larger deposits as node-positive.

PMID- 9641218
TI  - Five-year survival in patients with endometrioid carcinoma of the ovary versus
      those with serous carcinoma.
AB  - BACKGROUND: Ovarian carcinoma is the most deadly of gynecologic malignancies.
      Controversy exists as to whether different histologic types have a different
      prognosis. The goal of this study was to determine whether patients with
      endometrioid carcinoma of the ovary have a different prognosis than patients with
      serous carcinoma. METHODS: Available records for all patients on the gynecologic
      oncology service with epithelial ovarian carcinoma from January 1, 1981 through
      December 31, 1989, were reviewed. Patients with endometrioid ovarian carcinomas
      were matched with patients with serous carcinoma with regards to age, grade,
      stage, and level of cytoreduction. RESULTS: Forty-two patients were studied by
      matching 21 patients with endometrioid carcinoma with 21 patients with serous
      carcinoma. The 5-year survival of the 21 patients with endometrioid carcinoma was
      61.9% while the 5-year survival was 71.4% in the patients with serous carcinoma
      (P=0.22). Of the patients diagnosed with endometrioid carcinoma, the mean
      survival was 57 months versus a mean survival of 69 months in patients with
      serous carcinoma (P=0.30). Estrogen receptor levels were not statistically
      significantly different between the two groups (P=0.108); however, progesterone
      receptor levels did prove to be statistically significantly different (P<0.001).
      CONCLUSIONS: When patients with endometrioid and serous tumours of the ovary are
      matched for age, grade, stage and level of cytoreduction, there is no difference
      in either 5-year survival or length of survival.

PMID- 9641219
TI  - Effects of retinoic acid on the expression of a tumor rejection antigen (heat
      shock protein gp96) in human cervical cancer.
AB  - Retinoids are a class of compounds structurally related to vitamin A which have
      been found to be active agents experimentally as well as clinically in the
      prevention and treatment of cervical cancer. Recent data have suggested that in
      addition to their key regulatory role during epithelial cell differentiation,
      they could also contribute to enhanced cellular and humoral immunity against
      tumor cells. Hsp gp96 molecules have recently been implicated in the presentation
      of tumor and viral antigens. A number of key elements in this pathway, including
      major histocompatibility complex (MHC) class I molecules as well as adhesion/co
      stimulation molecules such as ICAM-1 have reported to be sensitive to retinoic
      acid up-regulation. In this study we analyzed at the transcriptional (Northern
      blot) and post-transcriptional levels (Western blot) the effects of retinoic acid
      on the expression of the tumor rejection antigen (heat shock protein gp96) in
      three human cervical carcinoma cell lines. Exposure of therapeutic doses of
      retinoic acid (i.e. 1 microM) significantly and consistently increased the
      expression of heat shock protein gp96 (Western blot analysis) on CaSki, SiHa and
      HT-3 cervical cancer cell lines. Northern blot analysis demonstrated that the
      increase in the amount of protein was due to the transcriptional upregulation of
      this gene. Taken together, our results show that retinoic acid can significantly
      increase the expression of yet another immunologically important cell molecule,
      the tumor rejection antigen heat shock protein gp96 in human cervical cancer.
      Such findings provide new information on the effects of retinoic acid on tumor
      cells and further support the role of retinoic acid as a powerful biologic
      response modifier.

PMID- 9641220
TI  - Concurrent cytogenetic and molecular investigations in uterine and ovarian
      neoplasms.
AB  - We studied a group of 24 uterine and ovarian neoplasms with the purpose to verify
      if any correlation could be established between chromosomal abnormalities, loss
      of heterozigosity (LOH) and microsatellite instability (MIN). Tumor specimens
      obtained from 24 women (12 affected by ovarian and 12 by uterine neoplasms) were
      split in two parts, one was used for short term cultures for cytogenetic
      investigation while from the second DNA was extracted for molecular studies. We
      studied 22 polymorphic loci from 19 chromosomes and compared the alleles observed
      in the tumor with those observed in the DNA obtained from peripheral blood.
      Extensive loss of heterozigosity was observed when total or partial chromosomal
      loss was observed in at least 50% of the examined cells; MIN did not correlate
      with any particular cytogenetic abnormality nor with LOH.

PMID- 9641221
TI  - The effect of fixation on the size, shape and summed optical density of
      endometrial cancer nuclei.
AB  - OBJECTIVE: Nuclear morphometric features have been shown to be of prognostic
      importance in several malignancies including recently, endometrial cancer. The
      authors attempted to see whether the type of fixation affected nuclear size
      (NUSZ), shape (NUSH), and summed optical density (NUSD). METHODS: Fifty
      specimens, half air dried and half alcohol fixed, were obtained from 25
      consecutive patients with endometrial cancer. Results were compared with the
      paired samples t-test. Differences among the nuclear morphometric features and
      histologic grade, stage, and depth of myometrial invasion were studied by one-way
      analysis of variance. Logistic regression was used to determine if any were
      independent prognostic features. Image analysis was used to determine NUSZ, NUSH,
      and NUSD. RESULTS: Mean NUSZ was shown to be significantly larger in air dried
      specimens (89.13 microm2) as compared to alcohol fixed specimens (80.34 microm2)
      P=0.047. Mean NUSH was significantly closer to round in air dried specimens
      (15.21) as compared to alcohol fixed specimens (15.65) P=0.025. There was no
      significant difference in mean NUSD between air dried (128.61) and alcohol fixed
      specimens (126.22) P=0.76. Stage, as well as air dried NUSZ, NUSH, and NUSD were
      all independent predictors of recurrence. In this study none of the nuclear
      parameters from the alcohol fixed tissues were predictive of recurrence.
      CONCLUSION: The type of fixation significantly affects the nuclear morphometric
      parameters of size and shape. While NUSZ, NUSH, and NUSD from air dried specimens
      were predictive of recurrence, the same parameters from alcohol fixed specimens
      were not. A larger prospective trial is currently underway to validate these
      findings.

PMID- 9641222
TI  - Well-differentiated versus less-differentiated endometrial carcinoma.
AB  - The aim of this study was to compare well-differentiated (grade 1) and less
      differentiated (grades 2 and 3) endometrial carcinoma, concerning clinical risk
      factors, presenting symptoms and operative findings. Seventy-one surgically
      staged endometrial carcinoma cases were reviewed and retrospectively divided
      according to tumor differentiation into two groups: grade 1 cases (Group I; n=40)
      and grade 2 and 3 cases (Group II; n=31). No difference was found between the two
      groups when comparing patient age, gravidity and parity, history of hypertension,
      diabetes or other malignancies, duration of menopause, number of patients
      receiving hormonal replacement therapy and histological type of tumor. There was
      also no difference in presenting symptoms or in duration of uterine bleeding up
      to the diagnosis of endometrial carcinoma. On the other hand, patients with well
      differentiated tumors, as compared to patients with less-differentiated
      endometrial carcinoma, were significantly more obese (p<0.02), had a smaller
      uterus (p<0.01) and presented with less advanced stage disease (p<0.0005). The
      fact that the age of the patients, as well as the duration of uterine bleeding
      before diagnosis, was similar in both groups may indicate that more advanced
      cases, as in group II, represent originally a more aggressive tumor rather than
      progression from a well-differentiated disease. This hypothesis needs further
      research.

PMID- 9641223
TI  - Cavernous haemangioma of the breast. A case report.

PMID- 9641224
TI  - Staging nodal growth in breast cancer on a histological basis.
AB  - This study describes the axillary tumour-load in 484 women with breast carcinoma
      with spread to one or more nodes. The aim was to relate tumour-load to nodal
      histology. The tumour area and that of residual lymphoid tissue was measured from
      standardised nodal sections. The presence/absence of tumor cells in the efferent
      vessels (EV) defined their nodal status as EV+ or EV-. The former has a poor
      prognosis. While the number of EV+ cases increased with the total tumour-load,
      the number of EV- cases decreased. In the EV+ there was high positive correlation
      between tumour-load and number of deaths from breast cancer, with a corresponding
      negative correlation in the EV-. Twice as many patients with EV+ nodes died of
      breast cancer compared to the EV- group. Investigation of 164 consecutive tumour
      bearing nodes showed a similar pattern. Irrespective of EV status the area of
      residual lymphoid tissue remained constant. Although the lymphoid area was
      similar the tumour-load was twice as high in the EV+ cases. These findings stress
      basic biological differences in the growth of breast carcinoma in the nodes.
      Patients with the smallest micrometastases that are found in the afferent
      lymphatics of the node and the EV+ patients in which tumour cells are present in
      the efferent nodal vessels have a poor short-term prognosis. The patients with
      larger micrometastases in the nodal lymphoid tissue and also EV- patients with
      the next highest tumour-load are both of low prognostic risk, with the exception
      of the few EV- with an exceptionally high tumour-load.

PMID- 9641225
TI  - Management of cervical intraepithelial neoplasia of the uterine cervix: 110 cases
      treated by cold-knife conization.
AB  - PURPOSE OF INVESTIGATION: The purpose of this study was to evaluate treatment by
      cold-knife-conization in women carriers of cervical intraepithelial neoplasia
      (CIN). METHODS: The histologic findings of pre-clinical neoplasia of the cervix
      after conization were compared to the previous findings of cytology, colposcopy
      and punch-biopsy in 110 women examined between 1985 and 1995. The chi square test
      (chi2) was used for the statistical analysis. RESULTS AND CONCLUSIONS: A close
      correlation is clinically important where complementary roles of these three
      methods are used to identify lesions suitable for local ablative therapy. The Pap
      test alone is no longer sufficient for the screening of the pre-cancerous lesion
      of the cervix and colposcopy is compulsory each time the smear is inadequate or
      altered. Conization permitted us to single out 13 (11.8%) cases of carcinoma.
      After cold-knife conization we had six (5.4%) recurrences within two years and
      two (1.8%) within three years. Our data show that conservative therapy by
      conization in women with CIN reduces the risk of invasive cancer of the cervix
      but careful follow-up of these patients is essential.

PMID- 9641226
TI  - Primary sarcoma of the ovary: report of five cases and review of the literature.
AB  - Primary ovarian sarcomas are rare and usually behave very aggressively. Over a
      ten-year period (1987-1996) five cases of primary ovarian sarcoma were managed at
      the Soroka Medical Center, Beer-Sheva, Israel. Four patients had malignant
      mullerian-mixed mesodermal tumor (MMMMT): two had Stage IIIC tumor with
      chondrosarcoma being the predominant sarcomatous element, one had Stage IIIC
      tumor with high-grade endometrioid stromal sarcoma (ESS) being the predominant
      sarcomatous element and one had Stage IC tumor with rhabdomyosarcoma being the
      predominant sarcomatous element. One patient had Stage IA leiomyosarcoma (LMS).
      All four patients with MMMMT received postoperative adjuvant chemotherapy,
      whereas the patient with LMS did not. The four patients with MMMMT died of their
      disease 10, 10, 13 and 25 months, respectively, after initial surgery. The
      patient with LMS died of intercurrent disease 21 months after initial surgery. It
      is concluded that most patients with primary ovarian sarcoma present with
      extraovarian disease and the prognosis is poor. The mainstay of treatment is
      debulking surgery consisting of total abdominal hysterectomy, bilateral salpingo
      oophorectomy and extirpation of tumor masses. The benefit of postoperative
      adjuvant chemotherapy and/or radiotherapy is still a subject of debate and has
      yet not been established.

PMID- 9641227
TI  - Angiogenic activity and interleukin-8 content of human ovarian cancer ascites.

PMID- 9641228
TI  - Intraperitoneal cisplatin-mitoxantrone and intravenous ifosfamide combination as
      first-line treatment of ovarian cancer.
AB  - Twenty-one chemotherapy naive ovarian cancer patients with stage III and minimal
      residual tumor were treated with cisplatin 75 mg/m2 and mitoxantrone 15 mg/m2
      (1st day) by intraperitoneal (i.p.) route and ifosfamide 4 g/m2 (15th day) by
      i.v. route every 4 weeks for a total of 6 cycles. Pathologic complete response
      (pCR) was achieved in 9/20 (45%, 95% Confidence Interval - CI - 23-68) of the
      patients. The median progression free interval (PFI) of the patients with pCR was
      45 (range: 18-70) months. For patients with residual tumor <1 cm (n: 11); pCR was
      82% and could be achieved only in this subgroup of patients. The cumulative (PFI)
      and overall survival rate of all patients at 3 years were 40% and 52%,
      respectively. The median PFI was found to be significantly different between the
      patients with residual tumor <1 cm (48 months, 95% CI 42-54) and 1-2 cm (9
      months, 95% CI 1-16) p<0.001. Main toxicities were emesis and abdominal pain
      which occurred in 53% and 65% of the courses, respectively. This combination
      seems to be an effective and feasible approach to previously untreated ovarian
      cancer patients with minimal tumor burden.

PMID- 9641229
TI  - Leiomyosarcomas of the small intestine misdiagnosed as ovarian masses: report of
      three cases.
AB  - Leiomyosarcomas of the small intestine are rare lesions. Because of their
      aspecific symptoms, diagnosis is often made at a late stage and, in women, must
      be distinguished from ovarian tumors. Three cases of large, abdominal masses,
      evaluated preoperatively as being ovarian tumors, are presented. At histology all
      three were diagnosed as leiomyosarcomas of the small intestine.

PMID- 9641230
TI  - Catheter complications associated with intraperitoneal chemotherapy.
AB  - Catheter complications associated with intraperitoneal chemotherapy were
      evaluated in 171 patients (pts) with primary intra-abdominal malignancies. In 96
      pts and 488 courses, single-use catheters (SUC) (3/G 14 Braun) were used between
      years 1990-1993. In 75 pts and 283 courses a semi-permanent subcutaneous
      implantable port and catheter system (SIPC) (T 2035/460 mm-F 14-76 Braun) was
      used between years 1993-1996. Cisplatin (60-75 mg/sqm), 5-fluorouracil (600
      mg/sqm), calcium folinate (150 mg), etoposide (180 mg/sqm), mitoxantrone (12-15
      mg/sqm) were given in various combinations and periods to patients with ovarian
      carcinoma (106 pts), gastrointestinal carcinoma (43 pts), hepatocellular
      carcinoma (17 pts) and mesothelioma (5 pts). The incidence of patients with
      complications was significantly higher in SUC (45%) than SIPC (23%) (p=0.001).
      Colon puncture (8.8%, p<0.0001) and subcutaneous leakage (3.7%, p<0.01) rate of
      the courses were significantly higher in SUC. Pain related to catheter
      complications (6%, p<0,0002), local infection (1.4%, p=0.02) and obstruction
      (1.4%, p=0.02) were significantly higher in SIPC. The most important local
      complications were intra-abdominal fibrosis and adhesions that were surgically
      documented in 90% of the ovarian cancer patients, and were more severe in
      patients with the SIPC system. The complication rate and the complication type of
      these two catheters were found to be significantly different in this
      retrospective analysis; in order to determine the real complication rate, safety,
      efficacy and overall acceptability of the catheters, a randomised trial is
      needed.

PMID- 9641231
TI  - A second primary malignancy in a cohort of patients with epithelial ovarian
      cancer--characteristics of diagnosis.
AB  - As the life expectancy of cancer patients has been extended because of earlier
      diagnosis and improved therapeutic modalities, second primary tumors are being
      diagnosed more frequently. We have examined the clinical characteristics of 38
      second primary tumors in a cohort of patients diagnosed with epithelial ovarian
      cancer in our department over a 6-year period. The most frequent neoplasm
      associations were in decreasing order of occurrence: ovary-breast, ovary
      endometrium, and ovary-gastro-intestinal tract. Most heterochronous second
      primary tumors have been diagnosed following patient symptoms and not during
      routine follow-up of patients with a known primary cancer. Family history was
      obtained for 30/38 patients (19 with full pedigrees and 11 with partial
      information). Two of these 30 patients (6.6%) had one affected first degree
      relative-one with ovarian cancer and one with breast cancer. With an increased
      risk of developing a second malignancy after having a previous tumor, closer
      surveillance of patients posttreatment for cancer is warranted.

PMID- 9641232
TI  - Primary pure choriocarcinoma of the ovary in reproductive ages: a case report.
AB  - Choriocarcinoma is an aggressive tumor with cyto- and syncytiotrophoblastic
      cells. It arises gestationally or nongestationally. Nongestational
      choriocarcinoma of the ovary can be pure or mixed with other germ cell tumors.
      Pure type is less frequent than mixed type and the diagnosis of nongestational
      choriocarcinoma of the ovary is very difficult in the reproductive period. A case
      of a 20-year-old woman with pure choriocarcinoma of the ovary is presented with a
      review of the literature and discussion of its origin.

PMID- 9641233
TI  - Stress and cervical dysplasia.
AB  - The aim of the study was to evaluate the relationship between personality, stress
      and cervical dysplasia. Twenty women with cervical dysplasia were compared to a
      control group of 23 healthy women. An evaluation of their personality was made by
      the 16 PF questionnaire; stressing events were investigated with the Paykel
      scale; hormonal repercussions were studied by using serum and urinary cortisol
      titers. Significant differences were found in intellectual capability and
      fancifulness, as well as in cortisol levels. Considering the significant issues
      that have emerged, we feel that this research is worthy of further investigation
      and that new evaluation parameters are necessary.

PMID- 9641234
TI  - Mucoepidermoid carcinoma of the breast.
AB  - Mucoepidermoid carcinomas are very rare breast tumors. The morphology of this
      breast tumour is similar to its counterpart in the salivary gland. The first two
      cases reported were low-grade and neither patient had metastatic disease.
      Furthermore, none of the five patients with low-grade mucoepidermoid carcinoma
      reported by Fisher had axillary lymph node involvement and were alive with no
      evidence of disease 4 to 10 years after diagnosis and were considered of probable
      favourable prognosis. A high grade form of mucoepidermoid cancer might occur in
      the breast as it does in the salivary gland. All high-grade variant cases
      published had demonstrable lymph node or distant metastases and rapidly fatal
      outcomes. This report describes a case of high-grade mucoepidermoid carcinoma of
      the breast with a disease-free interval of 5 years, despite of unfavourable
      histologic features at the time of diagnosis.

PMID- 9641235
TI  - A comparison of laparoscopic surgery with open procedure in endometrial cancer.
AB  - BACKGROUND: Laparoscopic hysterectomy and lymph node dissection have lately been
      reported as an alternative to an abdominal open procedure for the treatment of
      malignant gynaecological conditions. The laparoscopic operative technique has
      been evaluated and compared as to whether it is a safe, feasible and effective
      procedure. SUBJECTS: The study includes 78 women with indications for surgery for
      endometrial cancer stage I. A retrospective comparative study was undertaken at
      Baby Friendly Hospital, Kladno, in which 11 patients treated laparoscopically
      were compared with 26 patients treated by the open procedure of lymphadenectomy.
      We evaluated differences in the peri-and postoperative outcomes. RESULTS: All 11
      procedures were successfully completed. The mean operating time was 153 min, and
      mean blood loss was 130 ml. The median hospital stay was 4.7 days. There were no
      major complications. CONCLUSIONS: Laparoscopic hysterectomy and lymphadenectomy
      seem to be the procedures which result in a shorter hospital stay and rapid
      recovery. This approach could potentially decrease morbidity historically
      associated with hysterectomy and lymphadenectomy performed abdominally. Only
      prospective randomised studies will be able to demonstrate the ability of
      operative laparoscopy to improve contemporary management of endometrial cancer.

PMID- 9641236
TI  - Malignant ovarian tumors: conservative surgery and quality of life in young
      patients.
AB  - Better knowledge and adequate treatment of malignant ovarian tumors have improved
      the quality of life of young women--especially of child-bearing age. Nowadays
      preservation of ovarian function in women with tumors in early stage (I) or, in
      selected cases even in advanced stage (II-III), must be evaluated for
      conservative surgery (sometimes expressly requested by the patient herself). In
      our Institute we have followed this philosophy for many years and our experience
      confirms its value: 42 patients under age 40 (36 in stage I and 6 in advanced
      stage) underwent conservative surgery: 12 subsequently became pregnant and
      another 12 are able to conceive. Five- and ten-year survival rates are very good
      with 89.2% and 83.3% for all stages and 96.9% and 95% for early stages.

PMID- 9641237
TI  - High-risk gestational trophoblastic disease: analysis of clinical prognoses.
AB  - PURPOSE OF INVESTIGATION: An attempt to better define factors leading to patient
      survival in the high-risk group of malignant gestational trophoblastic disease
      (GTD). METHODS: From January 1, 1997 to December 31, 1995 25 cases of malignant
      high-risk GTD were retrospectively collected to evaluate prognostic factors by
      univariate and multivariate analysis. RESULTS: We identified the presence of
      liver metastases and/or brain metastases and the presence of intestinal
      metastases as significant by using univariate analysis. However, only the
      presence of liver metastases of brain metastases was significant by multivariate
      analysis (p=0.009). CONCLUSIONS: Although a high-risk group of GTD can be
      identified according to the modified World Health Organization (WHO) prognostic
      scoring system, liver metastases were not emphasized (only two points) in this
      scoring system. We suggested that these risk factors, including brain metastases
      and liver metastases, should be weighted more than other risk factors.

PMID- 9641238
TI  - Massive bilateral ovarian edema: report of 2 cases.
AB  - PURPOSE OF INVESTIGATION: Diagnostic and therapeutic approaches in two cases of
      bilateral massive ovarian edema were evaluated. METHODS: Two cases were
      retrospectively evaluated with the help of the medical reports. RESULTS: Both
      patients presented with left lower abdominal quadrant pain. Cystic pelvic masses
      were detected during abdomino-pelvic examination and confirmed with
      transabdominal ultrasonography. There were no abnormal laboratory results.
      Explorative laparotomy was performed with the diagnosis of torsion or rupture of
      ovarian tumor. Bilateral wedge resection with subsequent frozen section was
      performed. The final pathology was reported as bilateral massive ovarian edema.
      CONCLUSION: A diagnostic bilateral wedge resection with subsequent frozen section
      is essential in the management and confirmation of the diagnosis. As the vast
      majority of the cases are young, a conservative surgical management is mandatory
      to preserve ovarian function.

PMID- 9641239
TI  - Expression of ras p21 in the stromal cells of human neoplastic endometrium.
AB  - ras p21 proteins have been reported to take part in signal transduction through a
      cell membrane to the nucleus and they also play a crucial role in the process of
      carcinogenesis. Forty specimens of neoplastic endometrium, ten slides of normal
      endometrium and one case of uterine carcinosarcoma were investigated for ras p21
      expression in the stromal cells by immunohistochemistry. Stromal cells expressed
      ras p21 protein in 13 out of 40 (33%) cases of neoplastic endometrium. These
      cells were randomly dispersed wound the glandular crypts of the endometrium and
      were also detected in the adjacent myometrium surrounding the cancer tissue. When
      cancers were grouped by surgical stage, ras p21 protein was detected in 11/22
      (50%) of stage I, but only in 2/18 (11%) of stages II-IV according to FIGO. None
      of the stromal cells immunostained for p21 in normal endometrium or myometrium,
      however, a single case of carcinosarcoma expressed ras p21 within the stromal
      cells.

PMID- 9641240
TI  - nm23 expression in carcinoma of the uterine cervix.
AB  - To evaluate the significance of nm23 protein expression in cervical carcinoma, 83
      patients with stage IB disease, treated primarily with surgery were studied
      immunohistochemically. Of the cases 57 were squamous carcinoma, 9 were
      adenocarcinoma, 14 were adenosquamous carcinoma and 3 were small-cell carcinoma.
      nm23 expression was positive in 63% of the cases. Although positive expression
      was more common in squamous and adenosquamous type tumors, negative expression
      was dominant in adenocarcinoma (P<0.05). When nm23 expression was compared with
      the clinicopathologic risk factors, there was no correlation of expression with
      the grade, deep invasion of the stroma, parametrial involvement and lymph node
      metastasis. But expression was inversely correlated with the number of metastatic
      lymph nodes (P<0.05). Although 3 or more lymph node metastases is a very poor
      prognostic sign, nm23 expression was not correlated either with recurrence or
      survival. Expression was negative in 77% of metastatic lymph nodes and in all of
      the recurrences. The predominance of negative expression in metastatic lymph
      nodes (P<0.05) and recurrences seems to be related to the aggressive behavior of
      the negative clone in the heterogeneous primary tumor.

PMID- 9641241
TI  - Abnormal expression of cripto and p53 protein in endometrial carcinoma and its
      precursor lesions.
AB  - Many oncogenes and tumor suppressor genes are involved in multistep
      carcinogenesis. Cripto is an epidermal growth factor (EGF) related gene which
      shares homology with EGF and TGFalpha. The aim of this study was to evaluate the
      role of abnormal p53 and cripto oncogene expression in endometrial carcinogenesis
      and progression using a hyperplasia carcinoma sequence model. Ninety-six primary
      endometrial adenocarcinomas and 30 hyperplastic tissues of which 7 were atypical
      (AH), were immunohistochemically examined for the presence of cripto and abnormal
      p53 protein. Immunopositivity was compared in hyperplastic and carcinoma tissues
      and analysed for conventional clinicopathological prognostic variables such as
      grade, depth of myometrial invasion, lymphovascular invasion, lymph node
      metastases and clinical stage. Cripto immunoreactivity was strong in most cases
      of AH, and endometrial carcinomas revealed 71% overall and 41% strong positivity,
      while hyperplasias without atypia were weakly stained. There was no correlation
      between cripto expression and clinicopathological prognosticators. Abnormal p53
      was not observed in hyperplasias but AH and carcinomas expressed 14% and 25%
      overall positivity, respectively. There was a statistically significant
      correlation between the stage of the disease and abnormal p53 accumulation. Our
      results suggest that both cripto and p53 may play a role in endometrial
      carcinogenesis while abnormal p53 expression is an important parameter for
      disease progression.

PMID- 9641242
TI  - Human papilloma virus in verrucus carcinoma of the vulva: an immunopathological
      study of three cases.
AB  - The pathological features of three cases of verrucus carcinoma of the vulva,
      examined in our laboratory during the last decade are presented. Verrucus
      carcinoma of the vulva is of special interest because of its rarity (6.5% of our
      cases of malignant lesions of the vulva), its special morphology and the problems
      in differential diagnosis that are encountered. There is also evidence that there
      is an association with HPV infection. We present the pathological features of
      three cases of verrucus carcinoma that we studied in the last decade in our
      Laboratory among 48 malignant lesions of the vulva. An immunohistochemical
      detection of HPV was performed by the streptavidine-viotine method and
      classification by in situ hybridization showed the presence of HPV 6/11 in all
      cases.

PMID- 9641243
TI  - Brain electric microstates and momentary conscious mind states as building blocks
      of spontaneous thinking: I. Visual imagery and abstract thoughts.
AB  - Prompted reports of recall of spontaneous, conscious experiences were collected
      in a no-input, no-task, no-response paradigm (30 random prompts to each of 13
      healthy volunteers). The mentation reports were classified into visual imagery
      and abstract thought. Spontaneous 19-channel brain electric activity (EEG) was
      continuously recorded, viewed as series of momentary spatial distributions (maps)
      of the brain electric field and segmented into microstates, i.e. into time
      segments characterized by quasi-stable landscapes of potential distribution maps
      which showed varying durations in the sub-second range. Microstate segmentation
      used a data-driven strategy. Different microstates, i.e. different brain electric
      landscapes must have been generated by activity of different neural assemblies
      and therefore are hypothesized to constitute different functions. The two types
      of reported experiences were associated with significantly different microstates
      (mean duration 121 ms) immediately preceding the prompts; these microstates
      showed, across subjects, for abstract thought (compared to visual imagery) a
      shift of the electric gravity center to the left and a clockwise rotation of the
      field axis. Contrariwise, the microstates 2 s before the prompt did not differ
      between the two types of experiences. The results support the hypothesis that
      different microstates of the brain as recognized in its electric field implement
      different conscious, reportable mind states, i.e. different classes (types) of
      thoughts (mentations); thus, the microstates might be candidates for the 'atoms
      of thought'.

PMID- 9641244
TI  - The effect of attentional load on the breathing pattern in children.
AB  - Experiments designed to establish the effects of video games on breathing
      patterns have led to contradictory results. Several authors reported that video
      games tended to increase breathing frequency (i.e. to reduce breath duration),
      whereas others reported the opposite. We postulated that video games contain
      different psychophysiological components which may have opposite effects on
      breathing pattern. On the one hand, arousal and emotion may tend to stimulate
      breathing. On the other, focusing attention on the game may prompt subject to
      inhibit any movement--including breathing--which might be a potential nuisance
      variable. The aim of this study was to assess the specific effects of the
      attentional load in an experimental environment characterized by its low
      emotional impact. We measured breathing variables, cardiac frequency and cortisol
      levels in 10 healthy children (mean age = 9.2 +/- 1.5 years) who were familiar
      with the environment, the experimenter and the video game. Breath duration rose
      significantly, from 2.56 to 3.16 s, as a function of game difficulty. Cortisol
      levels, heart rate and the thoracic contribution to breathing displayed no
      significant changes. Taken together, these data suggest that focusing attention
      on the game tended to inhibit breathing and that previous contradictory reports
      in this respect were due to the confounding effects of emotion.

PMID- 9641245
TI  - Facial and emotional reactions to Duchenne and non-Duchenne smiles.
AB  - The purpose of the study was to investigate facial and emotional reactions while
      viewing two different types of smiles and the relation of emotional empathy to
      these reactions. Facial EMG was recorded from the orbicularis oculi and
      zygomaticus major muscle regions while subjects individually watched two blocks
      of stimuli. One block included posed facial expressions of the Duchenne smile (a
      felt smile) and a neutral face, the other block included expressions of another
      type of smile called non-Duchenne smile (an unfelt smile) and a neutral face.
      Emotional experiences were asked after each stimulus block. Finally, a measure of
      empathy was given. Facial EMG reactions differentiated between the neutral face
      and the Duchenne smile but not between the neutral face and the non-Duchenne
      smile. The Duchenne smile block induced experience of pleasure for the subjects
      who saw it as the first stimulus block. Empathy was correlated to the rated
      experiences of pleasure and interest after the Duchenne smile block.

PMID- 9641246
TI  - Fingertip temperature as an indicator for sympathetic responses.
AB  - Changes of acral skin blood flow are a commonly used indicator for sympathetic
      reflex responses to various stimuli. The goal of the present study was to
      determine whether decreases in fingertip temperature are indicative for
      sympathetic induced changes in microcirculation. Infrared thermography
      demonstrated that various stimuli triggering the sympathetic nervous system
      induced decreases in cutaneous microcirculation, most prominently in fingertip
      skin. Various such stimuli induced almost immediate temporary vasoconstriction,
      measured by laser Doppler flux and photoplethysmography. With a lag phase of
      approximately 15 s, reduced microcirculation was also reflected by a transient
      decrease in fingertip temperature. Vasoconstrictions were easily demonstrable by
      fingertip temperature when the starting fingertip temperature was above 32
      degrees C and vasoconstriction lasted at least 5 s. Temperature measurement
      offers the advantages of ease and simplicity of performance and analysis,
      compared with the more complex analyses of flux and pulse volume.

PMID- 9641247
TI  - ERPs, semantic processing and age.
AB  - ERPs (N400, LPC and CNV) were elicited in two sets of subjects grouped according
      to age (young vs. elderly) using a word-pair category matching paradigm. Each
      prime consisted of a Japanese noun (constructed from two to four characters of
      the Hiragana) followed by one Chinese character (Kanji) as the target, this
      latter representing one of five semantic categories. There were two equally
      probable target conditions: match or mismatch. Each target was preceded by a
      prime, either belonging to, or not belonging to, the same semantic category. The
      subjects were required to respond with a specified button press to the given
      target according to the condition. We found RTs to be longer in the elderly
      subjects and under the mismatch condition. N400 amplitude was reduced in the
      elderly subjects under the mismatch condition and there was no difference between
      match and mismatch response, which were similar in amplitude to that under match
      condition for the young subjects. In addition, the CNV amplitudes were larger in
      the elderly subjects. These results suggested that functional changes in semantic
      processing through aging (larger semantic networks and diffuse semantic
      activation) were the cause of this N400 reduction, attributing a subsidiary role
      to attentional disturbance. We also discuss the importance of taking age-related
      changes into consideration in clinical studies.

PMID- 9641248
TI  - Differences in heartbeat awareness among males with higher and lower levels of
      systolic blood pressure.
AB  - Recent empirical findings related to the baroreceptor hypothesis indicate that
      elevated heart rate, pulse pressure, and blood pressure may dampen exteroception
      and interoception. We thus predicted that persons with elevated systolic blood
      pressure would be less able to accurately perceive their heartbeats and profit
      from feedback training. This study examined the plausibility of this hypothesis
      by exposing 57 male students (11 with elevated SBP levels and 46 with
      normotensive SBP levels) to the Whitehead heartbeat perception task with, and
      without, feedback training. Results indicated that participants with elevated SBP
      levels were more able to accurately perceive their heartbeats prior to, and
      after, feedback training. Participants with elevated SBP levels also showed a
      significant increase in heartbeat perception accuracy when they were provided
      with feedback training while participants with normotensive blood pressure levels
      did not show a significant response to feedback training. These findings are
      interpreted in terms of the ballistic perception model of cardiac awareness.

PMID- 9641249
TI  - Electrophysiological evidence for the typicality effect of human cognitive
      categorization.
AB  - Event-related brain potentials (ERPs) were recorded from 14 normal subjects
      during a category verification task. Stimulus words were selected from 17
      semantic categories (e.g. 'vegetables'). Half of the words were typical category
      members (e.g. 'carrot', 'spinach') and the other half were atypical (e.g.
      'parsley', 'asparagus'). Subjects were required to judge whether each stimulus
      belonged to a target category ('vegetables' or 'sports') or a non-target
      category. For the non-target category, the typicality effect was neither found in
      ERPs nor in reaction times. For the target category, typical words were responded
      to more quickly than were atypical words and the ERP amplitudes between a 300-450
      ms period were more negative after the atypical words than after the typical
      words (typicality effect). These results suggested that typical words of the
      target were more primed by a target category than were the atypical words of the
      target and thus that a concept is represented by a prototype, the central
      tendency of all members of the category.

PMID- 9641250
TI  - Effects of a negative visual hypnotic hallucination on ERPs and reaction times.
AB  - The study of changes in ERPs provoked by negative hypnotic hallucinations has
      thus far yielded contradictory results. Most previous studies have failed to
      separate specific changes in the processing of the hallucinated stimuli from non
      specific changes in arousal due to hypnosis. The present study addresses this
      issue with the combination of two experimental effects in the task designed to
      test the hallucination: the noise-compatibility effect and the Simon effect. A
      choice reaction task was used in which targets appearing at either side of a
      screen were defined by color and were accompanied by irrelevant noise, and a
      negative hallucination suggestion was given for noise stimuli. Four highly
      hypnotizable subjects performed the task on two separate occasions, with and
      without the suggestion. Increases in reaction times and P300 latencies were found
      as a function of noise and spatial stimulus-response (SR) incompatibility (Simon
      effect). Suggestion decreased the response times for all types of trials non
      significantly, and it decreased significantly those of left-hand responses. On
      the other hand, suggestion reduced the increase in P300 latencies in noise
      incompatible trials, but did not influence the Simon effect. This result
      indicates a specific effect of suggestion in the processing of hallucinated
      stimuli, which is consistent with the hallucinatory experience reported by the
      subjects.

PMID- 9641251
TI  - A spatio-temporal analysis of recognition-related event-related brain potentials.
AB  - Words correctly recognized as previously studied (i.e. old) elicit greater
      amounts of positive event-related brain potential (ERP) activity over posterior
      scalp between 400 and 800 ms than do previously unstudied (i.e. new) words. While
      investigators have reported that this old/new effect consists of more than one
      subcomponent, the spatio-temporal parameters of these possible subcomponents, as
      well as any other patterns of brain activity associated with recognition, remain
      incompletely specified. Thus, ERPs were recorded from 32 scalp sites while 13
      subjects performed four repetitions of a study-test recognition paradigm. The
      subjects' task was to decide whether each word was old or new and press the
      appropriate button as quickly as possible. The timing and topography of the ERPs
      elicited by old and new words was assessed with topographic profile comparisons
      on the areas with a variety of temporal windows, and visualized with potential
      and CSD maps. The results revealed that seven patterns of ERP activity,
      dissociable on the basis of their topography, timing and response to experimental
      variables, were elicited between 300 and 2000 ms. Three of these appeared as
      subcomponents of the old/new effect (maximal over left medial frontal, left
      parietal-occipital and right central-frontal scalp), another was related to
      decision confidence and/or memory trace strength (maximal over left central
      scalp) and three others appeared to be related to more general aspects of
      recognition (maximal over the frontal poles, midline frontal scalp and right
      frontal scalp). Taken together, the seven distinct patterns of neural generator
      activity described here support the hypothesis that retrieval of information from
      episodic memory depends on a collection of different processes that occur in a
      temporally and spatially distributed neural circuit.

PMID- 9641252
TI  - Structure-activity relationships for antioxidant activities of a series of
      flavonoids in a liposomal system.
AB  - Structurally diverse plant phenolics were examined for their abilities to inhibit
      lipid peroxidation induced either by Fe(II) and Fe(III) metal ions or by azo
      derived peroxyl radicals in a liposomal membrane system. The antioxidant
      abilities of flavonoids were compared with those of coumarin and tert
      butylhydroquinone (TBHQ). The antioxidant efficacies of these compounds were
      evaluated on the basis of their abilities to inhibit the fluorescence intensity
      decay of an extrinsic probe, 3-(p-(6-phenyl)-I,3,5-hexatrienyl)phenylpropionic
      acid (DPH-PA), caused by the free radicals generated during lipid peroxidation.
      All the flavonoids tested exhibited higher antioxidant efficacies against metal
      ion-induced peroxidations than peroxyl-radical-induced peroxidation, suggesting
      that metal chelation may play a larger role in determining the antioxidant
      activities of these compounds than has previously been believed. Distinct
      structure-activity relationships were also revealed for the antioxidant abilities
      of the flavonoids. Presence of hydroxyl substituents on the flavonoid nucleus
      enhanced activity, whereas substitution by methoxy groups diminished antioxidant
      activity. Substitution patterns on the B-ring especially affected antioxidant
      potencies of the flavonoids. In cases where the B-ring could not contribute to
      the antioxidant activities of flavonoids, hydroxyl substituents in an catechol
      structure on the A-ring were able to compensate and become a larger determinant
      of flavonoid antioxidant activity.

PMID- 9641253
TI  - Clarification of the relationship between free radical spin trapping and carbon
      tetrachloride metabolism in microsomal systems.
AB  - It has been proposed that the C-phenyl-N-tert-butylnitrone/trichloromethyl
      radical adduct (PBN/.CCl3) is metabolized to either the C-phenyl-N-tert
      butylnitrone/carbon dioxide anion radical adduct (PBN/.CO2-) or the glutathione
      (GSH) and CCl4-dependent PBN radical adduct (PBN/[GSH-.CCl3]). Inclusion of
      PBN/.CCl3 in microsomal incubations containing GSH, nicotinamide adenine
      dinucleotide phosphate (NADPH), or GSH plus NADPH produced no electron spin
      resonance (ESR) spectral data indicative of the formation of either the PBN/[GSH
      .CCl3] or PBN/.CO2- radical adducts. Microsomes alone or with GSH had no effect
      on the PBN/.CCl3 radical adduct. Addition of NADPH to a microsomal system
      containing PBN/.CCl3 presumably reduced the radical adduct to its ESR-silent
      hydroxylamine because no ESR signal was observed. The Folch extract of this
      system produced an ESR spectrum that was a composite of two radicals, one of
      which had hyperfine coupling constants identical to those of PBN/.CCl3. We
      conclude that PBN/.CCl3 is not metabolized into either PBN/[GSH-.CCl3] or
      PBN/.CO2- in microsomal systems.

PMID- 9641254
TI  - Dose- and wavelength-dependent oxidation of crystallins by UV light--selective
      recognition and degradation by the 20S proteasome.
AB  - The lens of the human eye is a suitable model for age-related alterations at the
      molecular level. Age-related cataract formation is closely related to the
      accumulation of oxidatively altered proteins. In this study the influence of UV
      A, UV-B, and UV-C irradiation on the proteolytic susceptibility of alpha-, betaL
      , and betaH-crystallins by the isolated 20S proteasome was investigated. The
      proteins were irradiated with 280, 300, and 350 nm monochromatic light. Changes
      of the physical properties of the crystallins were characterized by absorbance
      measurements at 280 nm, fluorescence spectra, and SDS-PAGE-electrophoresis. The
      proteolytic susceptibility of crystallins was maximal after irradiation at 280 nm
      and three- to fivefold lower at 300 nm. Irradiation at 350 nm was not able to
      initiate proteolysis, probably due to protein-aggregate formation of higher
      molecular weight, as shown by SDS-PAGE. The damage of crystallins by UV-C light
      might be a signal for its proteolytic degradation by the 20S proteasome, whereas
      UV-B and UV-A do not increase the proteolytic susceptibility to the same extent
      but promote the formation of crosslinked proteins. Therefore, irradiation with
      UV, which is not followed by an increase in the proteolytic susceptibility, is
      accompanied by the formation of crosslinked proteins. It was concluded, that also
      long UV-B and UV-A may be involved in age-related alterations of the human lens
      and cataract formation.

PMID- 9641255
TI  - Cellular mechanisms of resistance to chronic oxidative stress.
AB  - Oxidative stress is implicated in several pathologies such as AIDS, Alzheimer's
      disease, and Parkinson's disease, as well as in normal aging. As a model system
      to study the response of cells to oxidative insults, glutamate toxicity on a
      mouse nerve cell line, HT-22, was examined. Glutamate exposure kills HT-22 via a
      nonreceptor-mediated oxidative pathway by blocking cystine uptake and causing
      depletion of intracellular glutathione (GSH), leading to the accumulation of
      reactive oxygen species and, ultimately, apoptotic cell death. Several HT-22
      subclones that are 10-fold resistant to exogenous glutamate were isolated and the
      mechanisms involved in resistance characterized. The expression levels of neither
      heat shock proteins nor apoptosis-related proteins are changed in the resistant
      cells. In contrast, the antioxidant enzyme catalase, but not glutathione
      peroxidase nor superoxide dismutase, is more highly expressed in the resistant
      than in the parental cells. In addition, the resistant cells have enhanced rates
      of GSH regeneration due to higher activities of the GSH metabolic enzymes gamma
      glutamylcysteine synthetase and GSH reductase, and GSH S-transferases activities
      are also elevated. As a consequence of these alterations, the glutamate resistant
      cells are also more resistant to organic hydroperoxides and anticancer drugs that
      affect these GSH enzymes. These results indicate that resistance to apoptotic
      oxidative stress may be acquired by coordinated changes in multiple antioxidant
      pathways.

PMID- 9641256
TI  - Involvement of oxidative stress in paraquat-induced metallothionein synthesis
      under glutathione depletion.
AB  - The inhibition of glutathione (GSH) synthesis by L-buthionine-SR-sulfoximine
      (BSO) causes aggravation of hepatotoxicity of paraquat (PQ), an oxidative-stress
      inducing substance, in mice. On the other hand, synthesis of metallothionein
      (MT), a cysteine-rich protein having radical scavenging activity, is induced by
      PQ, and the induction by PQ is significantly enhanced by pretreatment of mice
      with BSO. The purpose of present study is to examine whether generation of
      reactive oxygens is involved in the induction of MT synthesis by PQ under
      inhibition of GSH synthesis. Administration of PQ to BSO-pretreated mice
      increased hepatic lipid peroxidation and frequency of DNA single strand breakage
      followed by manifestation of the liver injury and induction of MT synthesis. Both
      vitamin E and deferoxamine prevented MT induction as well as lipid peroxidation
      in the liver of mice caused by administration of BSO and PQ. In cultured colon 26
      cells, both cytotoxicity and the increase in MT mRNA level caused by PQ were
      significantly enhanced by pretreatment with BSO. Facilitation of PQ-induced
      reactive oxygen generation was also observed by BSO treatment. These results
      suggest that reactive oxygens generated by PQ under inhibition of GSH synthesis
      may stimulate MT synthesis. GSH depletion markedly increased reactive oxygen
      generation induced by PQ, probably due to the reduced cellular capability to
      remove the radical species produced.

PMID- 9641257
TI  - Degradation of hyaluronic acid, poly- and monosaccharides, and model compounds by
      hypochlorite: evidence for radical intermediates and fragmentation.
AB  - Degradation of hyaluronic acid by oxidants such as HO. and HOCl/CIO- is believed
      to be important in the progression of rheumatoid arthritis. While reaction of
      hyaluronic acid with HO. has been investigated extensively, reaction with
      HOCl/ClO- is less well defined. Thus, little is known about the site(s) of
      HOCl/ClO- attack, the intermediates formed, or the mechanism(s) of polymer
      degradation. In this study reaction of HOCl/ClO- with amides, sugars,
      polysaccharides, and hyaluronic acid has been monitored by UV-visible (220-340
      nm) and EPR spectroscopy. UV-visible experiments have shown that HOCl/ClO- reacts
      preferentially with N-acetyl groups. This reaction is believed to give rise to
      transient chloramide (R-NCl-C(O)-R') species, which decompose rapidly to give
      radicals via either homolysis (to produce N. and Cl.) or heterolysis (one
      electron reduction, to give N. and Cl.) of the N--C bond. The nature of the
      radicals formed has been investigated by EPR spin trapping. Reaction of HOCl/ClO-
      with hyaluronic acid, chondroitin sulphates A and C, N-acetyl sugars, and amides
      gave novel, carbon-centered, spin adducts, the formation of which is consistent
      with selective initial attack at the N-acetyl group. Thus, reaction with
      hyaluronic acid and chondroitin sulphate A, appears to be localized at the N
      acetylglucosamine sugar rings. These carbon-centered radicals are suggested to
      arise from rapid rearrangement of initial nitrogen-centered radicals, formed from
      the N-acetyl chloramide, by reactions analogous to those observed with alkoxyl
      radicals. The detection of increasing yields of low-molecular-weight radical
      adducts from hyaluronic acid and chondroitin sulphate A with increasing HOCl/ClO
      concentrations suggests that formation of the initial nitrogen-centered species
      on the N-acetylglucosamine rings, and the carbon-centered radicals derived from
      them, brings about polymer fragmentation.

PMID- 9641258
TI  - Functional activity of blood polymorphonuclear leukocytes as an oxidative stress
      biomarker in human subjects.
AB  - In the present work, we studied the role of polymorphonuclear leukocytes (PMN) in
      aged individuals and coronary heart disease (CHD)-bearing patients, two
      physiopathological processes associated with overproduction of reactive oxygen
      species (ROS). The effects of antioxidant supplementation on the functional
      activity of PMN from CHD patients were also determined. The function of PMNs was
      evaluated by measuring of phagocytosis, killing activity, and ROS production.
      Luminol amplified chemiluminescence (CL) was used to estimate ROS production by
      stimulated PMNs. Total cholesterol and the LDL-cholesterol fraction from CHD
      patients were found to be higher than those recommended, returning to normal
      levels after antioxidant therapy. PMN CL of CHD patients was found to be higher
      than the associated control groups. Antioxidant therapy administrated to CHD
      patients lead to an increase in the killing activity accompanied by a decrease in
      PMN CL of these subjects. The study also showed that killing activity of PMN from
      human subjects over 60 years was significantly lower than the activity measured
      in younger subjects. PMN CL produced after stimulation was found to be positively
      correlated with the increasing age of human subjects (r=.946, p < .01).

PMID- 9641259
TI  - Structural aspects of the inhibitory effect of glabridin on LDL oxidation.
AB  - The inhibitory effects of glabridin, an isoflavan isolated from licorice
      (Glycyrrhiza glabra) root, and its derivatives on the oxidation of LDL induced by
      copper ions or mediated by macrophages were studied, in order to evaluate the
      contribution of the different parts of the isoflavan molecule to its antioxidant
      activity. The peak potential (E1/2) of the isoflavan derivatives, their radical
      scavenging capacity toward 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical and
      their ability to chelate heavy metals were also analyzed and compared to their
      inhibitory activity on LDL oxidation. In copper ion-induced LDL oxidation,
      glabridin (1), 4'-O-methylglabridin (2), hispaglabridin A (3), and hispaglabridin
      B (4), which have two hydroxyl groups at positions 2' and 4' or one hydroxyl at
      position 2' on ring B, successfully inhibited the formation of conjugated dienes,
      thiobarbituric acid reactive substances (TBARS) and lipid peroxides, and
      inhibited the electrophoretic mobility of LDL under oxidation. Compounds 1-3
      exhibited similar activities, whereas compound 4 was less active. In macrophage
      mediated LDL oxidation, the TBARS formation was also inhibited by these
      isoflavans (1-4) at a similar order of activity to that obtained in copper ion
      induced LDL oxidation. On the other hand, 2'-O-methylglabridin (5), a synthesized
      compound, whose hydroxyl at 2'-position is protected and the hydroxyl at 4'
      position is free, showed only minor inhibitory activity in both LDL oxidation
      systems. 2',4'-O-Dimethylglabridin (6), whose hydroxyls at 2'- and 4'-positions
      are both protected, was inactive. Resorcinol (7), which is identical to the
      phenolic B ring in glabridin, presented low activity in these oxidation systems.
      The isoflavene glabrene (8), which contains an additional double bond in the
      heterocyclic C ring, was the most active compound of the flavonoid derivatives
      tested in both oxidation systems. The peak potential of compounds 1-5 (300
      microM), tested at pH 7.4, was similar (425-530 mV), and that for compound 6 and
      8 was 1078 and 80 mV, respectively. Within 30 min of incubation, compounds 1, 2,
      3, 4, 8 scavenged 31%, 16%, 74%, 51%, 86%, respectively, of DPPH radical, whereas
      compounds 5 and 6, which almost did not inhibit LDL oxidation, also failed to
      scavenge DPPH. None of the isoflavan derivatives nor the isoflavene compound were
      able to chelate iron, or copper ions. These results suggest that the antioxidant
      effect of glabridin on LDL oxidation appears to reside mainly in the 2' hydroxyl,
      and that the hydrophobic moiety of the isoflavan is essential to obtain this
      effect. It was also shown that the position of the hydroxyl group at B ring
      significantly affected the inhibitory efficiency of the isoflavan derivatives on
      LDL oxidation, but did not influence their ability to donate an electron to DPPH
      or their peak potential values.

PMID- 9641260
TI  - Effect of the peroxisome proliferator ciprofibrate on lipid peroxidation and 8
      hydroxydeoxyguanosine formation in transgenic mice with elevated hepatic catalase
      activity.
AB  - Peroxisome proliferators are a group of non-genotoxic hepatic carcinogens which
      have been proposed to act by increasing oxidative damage in the liver. To test
      this hypothesis, we have produced a transgenic mouse line that has elevated
      catalase activity specifically in the liver. In this study, we have examined if
      catalase overexpression influences the induction of lipid peroxidation or
      oxidative DNA damage, two mechanisms which have been hypothesized to be important
      in the carcinogenesis by peroxisome proliferators. Transgenic mice or non
      transgenic litter mates were fed either 0.01% ciprofibrate or a control diet for
      21 days. The activities of fatty acyl CoA oxidase and lauric acid hydroxylase
      were not significantly affected by catalase overexpression, although the ratio of
      fatty acyl CoA oxidase to catalase was significantly decreased in transgenic
      animals. Hepatic lipid peroxidation was estimated by quantifying the
      concentrations of malondialdehyde and conjugated dienes. Ciprofibrate treatment
      did not affect either endpoint, but catalase overexpression increased the
      concentrations of malondialdehyde (in untreated mice only) and conjugated dienes
      (in both untreated and ciprofibrate-fed mice). Oxidative DNA damage was estimated
      by quantifying 8-hydroxydeoxyguanosine (8-OHdG) by high-performance liquid
      chromatography/electrochemical detection. Ciprofibrate treatment significantly
      increased hepatic 8-OHdG concentrations, in agreement with several previous
      studies, but catalase overexpression did not significantly affect them, although
      8-OHdG concentrations were decreased 50% in untreated mice. These results imply
      that the metabolism of hydrogen peroxide by catalase is not an important factor
      in the development of hepatic lipid peroxidation. The decrease in hepatic 8-OHdG
      in untreated transgenic mice and the increase seen after ciprofibrate
      administration imply that hydrogen peroxide is important in the formation of 8
      OHdG. While the lack of decreased 8-OHdG levels in ciprofibrate-treated
      transgenic mice does not support this conclusion, it is possible that catalase
      levels were not sufficiently high to affect this endpoint. Transgenic mice with
      higher hepatic catalase activities may be required to resolve this issue.

PMID- 9641261
TI  - Cytotoxicity-associated effects of reactive oxygen species on endothelin-1
      secretion by pulmonary endothelial cells.
AB  - In this study bovine pulmonary artery endothelial cells (BPAEC) were used as a
      model system to investigate the effects of the hypoxanthine-xanthine oxidase
      (HXXO) oxygen radical donor system on ET-1 secretion into pulmonary vasculature.
      Incubation of BPAEC with HXXO for 4 h caused a significant reduction in ET-1
      secretion, which was significantly offset by allopurinol or catalase, but not by
      Cu/Zn superoxide dismutase (SOD). ET-1 secretion was also reduced by H2O2, and
      this effect was again significantly offset by catalase. XO alone also reduced ET
      1 secretion, but to a significantly lesser degree than did HXXO, and this effect
      was not offset by allopurinol, catalase, or SOD. None of the oxidant treatments
      were associated with a loss of immunoreactive ET-1 from endothelial cell medium
      containing synthetic peptide. The HXXO- and H2O2-mediated reductions in ET-1
      secretion were accompanied by evidence of reduced cell viability. This loss of
      viability was absent when cells were treated with HXXO + catalase, allopurinol,
      or mercaptopropionyl glycine, but not when SOD was present. We conclude that
      under conditions of oxidative stress, the pulmonary vascular endothelium responds
      by secreting less ET-1. This may be relevant to its vasodilator functions in the
      pulmonary vasculature, which would therefore be compromised when the endothelium
      is exposed to oxidant stress.

PMID- 9641262
TI  - Interleukin-1 expression during hyperoxic lung injury in the mouse.
AB  - An important component of the pathophysiologic response to hyperoxia (O2) is
      pulmonary inflammation, although the roles of specific inflammatory mediators
      during pulmonary O2 toxicity are not completely known. Interleukin-1 (IL-1) is an
      early inflammatory mediator and is sufficient to elicit many of the responses
      associated with acute injury. The IL-1 family comprises two bioactive proteins,
      IL-1alpha and IL-1beta, and their natural antagonist IL-1ra. Here we report
      studies of IL-1 regulation during hyperoxic lung injury in the adult mouse. When
      assayed by Northern blot, increases in IL-1beta mRNA were seen after 2 days of
      hyperoxia. In contrast, IL-1alpha mRNA was barely detectable before 4 days of
      hyperoxia. To further understand the cellular origin of IL-1beta expression in
      lungs, in situ hybridization and immunohistochemical analyses were performed. IL
      1beta mRNA or protein was not detected in the lungs of unexposed animals. At 3
      days, we observed the accumulation of IL-1beta transcripts in pulmonary
      interstitial macrophages and in a subset of neutrophils, and immunodetectable IL
      1beta protein was co-localized in adjacent sections. At 4 days of exposure, IL
      1beta transcripts were widespread in lung tissue, but many areas rich in IL-1beta
      mRNA were devoid of immunodetectable IL-1beta. However, it is not known whether
      increased synthesis of IL-1beta or the uncoupling of IL-1beta protein and mRNA
      accumulation has a role in pathophysiology of pulmonary O2 toxicity.

PMID- 9641263
TI  - Effect of naturally occurring flavonoids on lipid peroxidation and membrane
      permeability transition in mitochondria.
AB  - The ability of eight structurally related naturally occurring flavonoids in
      inhibiting lipid peroxidation and mitochondrial membrane permeability transition
      (MMPT), as well as respiration and protein sulfhydryl oxidation in rat liver
      mitochondria, was evaluated. The flavonoids tested exhibited the following order
      of potency to inhibit ADP/ Fe(II)-induced lipid peroxidation, estimated with the
      thiobarbituric acid assay: 3'-O-methyl-quercetin > quercetin > 3,5,7,3',4'-penta
      O-methyl-quercetin > 3,7,3',4'-tetra-O-methyl-quercetin > pinobanksin > 7-O
      methyl-pinocembrin > pinocembrin > 3-O-acyl-pinobanksin. MMPT was estimated by
      the extent of mitochondrial swelling induced by 10 microM CaCl2 plus 1.5 mM
      inorganic phosphate or 30 microM mefenamic acid. The most potent inhibitors of
      MMPT were quercetin, 7-O-methyl-pinocembrin, pinocembrin, and 3,5,7,3',4'-penta-O
      methyl-quercetin. The first two inhibited in parallel the oxidation of
      mitochondrial protein sulfhydryl involved in the MMPT mechanism. The most potent
      inhibitors of mitochondrial respiration were 7-O-methyl-pinocembrin, quercetin,
      and 3'-O-methyl-quercetin while the most potent uncouplers were pinocembrin and 3
      O-acyl-pinobanksin. In contrast 3,7,3',4'-tetra-O-methyl-quercetin and
      3,5,7,3',4'-penta-O-methyl-quercetin showed the lowest ability to affect
      mitochondrial respiration. We conclude that, in general, the flavonoids tested
      are able to inhibit lipid peroxidation on the mitochondrial membrane and/or MMPT.
      Multiple methylation of the hydroxyl substitutions, in addition to sustaining
      good anti-lipoperoxidant activity, reduces the effect of flavonoids on
      mitochondrial respiration, and therefore, increases the pharmacological potential
      of these compounds against pathological processes related to oxidative stress.

PMID- 9641264
TI  - Effects of a novel, low-molecular weight inhibitor of lipid peroxidation on
      ischemia-reperfusion injury in isolated rat hearts and in cultured
      cardiomyocytes.
AB  - We investigated the effect of H290/51, a novel, low-molecular-weight inhibitor of
      lipid peroxidation, on cardiac ischemia-reperfusion injury. Lactate dehydrogenase
      (LD) release from cultured cardiomyocytes exposed to 1 h hypoxia and 4 h
      reoxygenation was measured after pretreatment with different concentrations of
      H290/51. In another series, Langendorff-perfused rat hearts were exposed to 30
      min global ischemia and 60 min reperfusion (n=minimum 10 in each group): 1.
      Control ischemia-reperfusion. 2. Vehicle throughout the experiment. 3. Vehicle
      during stabilization, and H290/51 (10(-6) mol/l) during reperfusion. 4. H290/51
      throughout the experiments. During reoxygenation of isolated cardiomyocytes,
      H290/51 dose dependently inhibited LD release with an pIC50 value of 7.2+/-0.4
      (mean+/-SEM), with 10(-6) mol/l as the lowest efficient concentration. In
      isolated hearts ischemia-reperfusion induced severe reperfusion arrhythmias,
      reduced left ventricular developed pressure (LVDP) and coronary flow (CF), and
      increased LV end-diastolic pressure (LVEDP). LD activity in the effluent
      increased. H290/51 throughout perfusion (group 4) reduced the occurrence of
      severe reperfusion arrhythmias (p < .0001), attenuated the decrease of LVDP (p <
      .008), and CF (p < .006), the increase of LVEDP (p < .008), and the release of LD
      (p < .002). Tissue contents of thiobarbituric acid-reactive substances did not
      increase during reperfusion in controls, but was reduced in group 4 (p < .004).
      H290/51 given only during reperfusion (group 3) tended to improve cardiac
      function, but significantly so only for increase of CF (p < .01). The lipid
      peroxidation inhibitor H290/51 attenuated cardiac injury induced by ischemia
      reperfusion.

PMID- 9641265
TI  - Histochemical localization of superoxide dismutase activity in rat brain.
AB  - Histochemical localization of superoxide anion (O2.-) scavenging activity in rat
      brain was visualized by the tissue-blotting technique. The activity was thought
      to mainly depend on Cu/Zn-SOD, because the localization of the activity was
      identical with the immunohistochemistry of Cu/Zn-SOD and the localization of its
      mRNA in the brain. Moreover, the activity was dramatically decreased after
      treatment of Cu (I) chelater. The activity was detected in pyramidal cells of the
      cortex, granular, and mitral cells of the olfactory bulbs, pyramidal cell layer
      CA1 to CA3, and dentate gyrus of hippocampus formation and granular cells of the
      cerebellum. Moreover, the activity was detected in the pontine nuclei of brain
      stem. Olfactory bulbs, hippocampus, and cerebellum were believed to be bestowed
      high brain functions, i.e., long-term potentiation and long-term depression. A
      part of the function was regulated by a retrograde neurotransmitter, nitric oxide
      (.NO). Our findings suggest that the SOD is colocalized with NO synthase in
      olfactory bulbs, hippocampus, and cerebellum, where .NO plays the important
      roles. In contrast, low SOD activity was observed in the axonal neurofiber
      bundles, although the regions contain a lot of membrane lipids, which was thought
      to be peroxidized by O2.- and related radicals such as .OH in the regions. From
      these findings, it was suggested that the SOD did not only play a role in
      protecting the neurons from endogenously formed O2.-, but also play a role in
      preservation of beneficial natures of .NO in the brain.

PMID- 9641266
TI  - Alterations of antioxidant enzymes and oxidative damage to macromolecules in
      different organs of rats during aging.
AB  - Oxygen free radicals have been hypothesized to play an important role in the
      aging process. To investigate the correlation between the oxidative stress and
      aging, we have determined the levels of oxidative protein damage and lipid
      peroxidation in the brain and liver, and activities of antioxidant enzymes in the
      brain, liver, heart, kidney, and serum from the Fisher 344 rats at ages of 1, 6,
      12, 18, and 24 months. The results showed that the level of oxidative protein
      damage (measured as carbonyl content) in the brain and liver was significantly
      higher in older animals than in young animals. No statistical difference was
      observed in the lipid peroxidation of the liver and brain between young and old
      animals. The activities of antioxidant enzymes in most tissues displayed an age
      dependent decline. Superoxide dismutases in the heart, kidney, and serum,
      glutathione peroxidase activities in the serum and kidney, and catalase
      activities in the brain, liver, and kidney, significantly decreased during aging.
      Cytochrome c oxidase, an enzyme involved in electron transport in mitochondria,
      initially increased, but subsequently decreased in the aged brain, whereas no
      significant alteration was observed in the liver mitochondrial antioxidant
      enzymes. The present studies suggest that the accumulation of oxidized proteins
      during aging is most likely to be linked with an age-related decline of
      antioxidant enzyme activities, whereas lipid peroxidation is less sensitive to
      predict the aging process.

PMID- 9641267
TI  - Antioxidant defenses influence HIV-1 replication and associated cytopathic
      effects.
AB  - HIV-infected cells often exhibit reduced levels of antioxidant enzymes and
      thiols. To investigate the role of cellular antioxidant defenses in the
      progression of an acutely spreading HIV-1 infection, human Sup-T1 T cells were
      engineered to overexpress the selenium-dependent glutathione peroxidase, GSHPx-1.
      This enzyme represents a major cellular defense mechanism against toxicity
      associated with reactive oxygen species (ROS). T cells engineered to produce
      elevated GSHPx-1 activity displayed accelerated viral replication and associated
      cytopathic effects compared to control cells. Conversely, the inhibition of the
      synthesis of glutathione with buthione sulfoximine (BSO) resulted in the
      attenuation of viral replication in Sup-T1 cells. Similarly, exposure of human
      peripheral blood lymphocytes (PBLs) to low, nontoxic levels of BSO resulted in an
      approximately 80% decline in HIV-1 replication as indicated by Western blot
      analysis of viral proteins.

PMID- 9641268
TI  - Formation of keto and hydroxy compounds of linoleic acid in submitochondrial
      particles of bovine heart.
AB  - To observe lipid peroxidation of additive-free submitochondrial particles, we
      incubated submitochondrial particles in the absence of exogenous irons and t
      butyl hydroperoxide. After the incubation, the phospholipids were hydrolyzed by
      phopholipase A2, and the fatty acid constituents were analyzed by high
      performance liquid chromatography, gas chromatography-mass spectrometry, and
      liquid chromatography-mass spectrometry. Contrary to a commonly accepted theory,
      lipid peroxidation in the submitochondrial particles did not need the addition of
      NADH. In the phospholipid constituent fatty acids of the oxidized
      submitochondrial particles, derivatives of hydroperoxides of linoleic acid such
      as keto, hydroxy, trihydroxy, and hydroxyepoxy compounds were generated. Lipid
      peroxidation in the submitochondrial particles was not inhibited by the addition
      of catalase, superoxide dismutase, hydroxyl radical scavengers, or
      ethylenediaminetetraacetic acid, but was inhibited by the addition of KCN,
      antimycin-A, NADH, ubiquinol, deferoxamine mesylate, ascorbic acid, and alpha
      tocopherol. The cardiolipin-cytochrome c lipid peroxidation system could mimic
      the lipid peroxidation of the submitochondrial particles, in terms of linoleic
      acid products and the inhibitory patterns of radical scavengers and electron
      transfer chain inhibitors. Thus, lipid peroxidation in the submitochondrial
      particles seems to be due to phospholipid-hemoprotein lipid peroxidation systems
      such as the cardiolipin-cytochrome c system.

PMID- 9641269
TI  - Transgenic mice with elevated level of CuZnSOD are highly susceptible to malaria
      infection.
AB  - Copper/zinc superoxide dismutase (CuZnSOD) catalyses the conversion of O2.- into
      H2O2. Constitutive overexpression of CuZnSOD in cells and animals creates an
      indigenous oxidative stress that predisposes them to added insults. In this
      study, we used transgenic CuZnSOD (Tg-CuZnSOD) mice with elevated levels of
      CuZnSOD to determine whether overexpression of CuZnSOD affected the
      susceptibility of these mice to plasmodium infection. Acute malaria is associated
      with oxidative stress, mediated by redox-active iron released from the infected
      RBC. Two independently derived Tg-CuZnSOD lines showed higher sensitivity than
      control mice to infection by Plasmodium berghei (P. berghei), reflected by an
      earlier onset and increased rate of mortality. Nevertheless, while Tg-CuZnSOD
      mice were more vulnerable than control mice, the levels of parasitemia were
      comparable in both strains. Moreover, treatment of infected red blood cells (RBC)
      with oxidative stress inducers, such as ascorbate or paraquat, reduced the
      viability of parasites equally in both transgenic and control RBC. This further
      confirms that increased CuZnSOD does not support plasmodia development. The data
      are consistent with the possibility that the combination of increased redox
      active iron and elevated H2O2 in the plasmodium-infected Tg-CuZnSOD mice, led to
      an enhanced Fenton's reaction-mediated HO. production, and the resulting
      oxidative injury renders the transgenic mice more vulnerable to parasite
      infection.

PMID- 9641270
TI  - Nitric oxide in arthritis.
AB  - Nitric oxide's (NO) involvement in arthritis was first demonstrated when levels
      of nitrite, a stable endproduct of NO metabolism, were shown to be elevated in
      serum and synovial fluid samples of rheumatoid and osteoarthritis patients. NO
      production by chondrocytes, its involvement in various biochemical events of
      cartilage metabolism, and the in vivo suppression of experimental arthritis by NO
      synthase inhibitors further implicated NO in arthritis. However, a conclusive
      role for NO in the pathogenesis of arthritis remains to be defined, in contrast
      to the NO-cGMP signal transduction pathway of endothelium-mediated vasodilation.
      It appears that NO has limited modulating effects in cartilage metabolism, with
      evidence for both protective and deleterious effects. Recent developments that
      contribute to our understanding of NO's role in arthritis are discussed.

PMID- 9641271
TI  - Singlet molecular oxygen ((1)O2): a possible effector of eukaryotic gene
      expression.
AB  - Biological processes involving light may have both beneficial (photosynthesis)
      and destructive (photosensitization) consequences. Singlet molecular oxygen,
      (1)O2, and other reactive oxygen species such as hydrogen peroxide and hydroxyl
      radical, arise during the interaction of light with photosensitizing chemicals in
      the presence of molecular oxygen. (1)O2 oxidizes macromolecules such as lipids,
      nucleic acids, and protein, depending on its intracellular site of formation; and
      promotes detrimental processes such as lipid peroxidation, membrane damage, and
      cell death. Photochemical reactive oxygen species (ROS) generating systems induce
      the expression of several eukaryotic genes, which include stress proteins, early
      response genes, matrix metalloproteinases, immunomodulatory cytokines, and
      adhesion molecules. These gene expression phenomena may belong to cellular
      defensive mechanisms, or may promote further injury. Whereas the signal
      transduction pathways that link site-specific oxidative damage and gene
      expression are poorly understood, ROS may affect signalling components in the
      membrane, cytosol, or nucleus, leading to changes in phospholipase,
      cyclooxygenase, protein kinase, protein phosphatase, and transcription factor
      activities. Limited evidence for (1)O2 involvement in gene activation phenomena
      consists of deuterium oxide solvent effects, inhibition by (1)O2-quenchers,
      sensitization by porphyrins, chemical trapping methods, and comparative effects
      of photosensitizing dyes and thermolabile endoperoxides. The studies outlined in
      this review support an hypothesis that (1)O2 and other ROS generated during
      photochemical processes such as ultraviolet-A (320-380 nm) radiation exposure, or
      photosensitizer mediated oxidation may have dramatic effects on eukaryotic gene
      expression.

PMID- 9641272
TI  - Autocatalytic oxidation of hemoglobin by nitrite: a possible mechanism.
AB  - Oxidation of oxyhemoglobin by nitrite ions to produce methemoglobin is one of the
      more employed procedures to oxidize the hemoprotein. The process takes place
      readily after a clear induction time. This behaviour is usually explained in
      terms of an autocatalytic reaction mechanism. However, the generally accepted
      mechanism is not autocatalytic and cannot explain the main features of the
      process. In the present work it is proposed that the characteristics of the
      process require the occurrence of a fast reaction between oxyhemoglobin and
      nitrogen dioxide. This process acts as a branching step, leading to the observed
      autocatalysis.

PMID- 9641273
TI  - Treating recurrence of parotid benign pleomorphic adenomas.
AB  - Treatment for recurrence after surgical removal of parotid benign pleomorphic
      adenoma (PBPA) has not been well defined and is often followed by further
      recurrence. Surgery is overwhelmingly the most common approach. The risk of
      facial nerve injury is greater at reoperation since the nerve is less well
      defined. The value of radiation therapy (RT) has not been determined and incurs
      with it the risk of possible late occurrence of malignancy or nerve damage. The
      charts of patients with recurrent PBPA treated consecutively by a single surgeon
      from 1965 to 1993 were reviewed. All patients had a histopathologically verified
      diagnosis of PBPA both at the time of primary and subsequent surgeries. Follow-up
      was obtained from clinical charts and correspondence communication. Recurrence
      curves were generated using the Kaplan-Meier method. Thirty-nine patients with
      recurrent PBPA (36 referred and 3 treated primarily at Mayo) were evaluated. The
      patients were classified according to the type of surgery: 14 patients had
      previously undergone some form of parotidectomy or had only resection of the
      tumor for recurrence, and 25 patients underwent parotidectomy since this had not
      been performed primarily. The mean age in the two groups was 49 and 50 years
      respectively. The mean follow-up was 10 years after the recurrence treatment. The
      mean time between initial resection and recurrence in the two groups was 14 and
      15 years. The mean time between the recurrence treatment and a second recurrence
      was 7.5 years. Nine patients had RT in addition to the local resection. Of this
      group 3 patients (33%) developed another recurrence. Five patients had local
      resection only, and of this group 1 patient (20%) developed another recurrence.
      Of the group that had superficial parotidectomy, 3 patients had additional RT and
      one of these patients (33%) developed another recurrence. Twenty-two patients had
      superficial parotidectomy only, and of this group 3 patients (14%) developed
      another recurrence. Only 2 of the 39 patients had complications. One patient
      developed Frey's syndrome after superficial parotidectomy and 1 patient developed
      facial paralysis after RT. As in other series, the number of patients is
      inadequate to allow for firm conclusions. However, it appears that when previous
      parotidectomy has been performed, simple excision with a margin of surrounding
      tissue would seem appropriate. Parotidectomy should be carried out if not
      performed previously. In simple excision after previous parotidectomy, there is a
      greater risk to the facial nerve because of difficulty in distinguishing the
      facial nerve from surrounding scar tissue. Our preference is to use general
      anesthesia so that branches of the nerve are not paralyzed and stimulation of the
      nerve aids in safe dissection. The value of RT is still indeterminate.

PMID- 9641274
TI  - Advantages of sharp adventitial dissection for microvascular anastomoses.
AB  - Adventitia is usually removed from arteries to simplify microvascular
      anastomoses. Some surgeons peel the adventitia away bluntly whereas others trim
      the adventitia sharply with scissors. We used a rat cremaster flap for intravital
      microscopy to evaluate these two techniques. Animals with unmanipulated vessels,
      without anastomosis or adventitial removal, served as controls. Fifty-four rats
      were studied in three groups of 18 rats. Functional capillary density, red blood
      cell velocity, diameter of the flap's feeding artery (A1), microthrombi
      formation, and neutrophilic activity were studied for 5 hours following
      anastomosis, and 24 and 72 hours later. Histological changes in blunt and sharply
      prepared arteries were compared with control vessels. After blunt preparation,
      capillary perfusion was reduced to 61% of control values (p < 0.05) and A1
      diameter was reduced to 77% of control values (p < 0.05). Capillary perfusion and
      A1 diameter were unchanged in sharply prepared arteries. Architectural changes in
      the vessel wall were more profound, and neutrophilic activity was increased in
      bluntly prepared arteries. In this study, sharp preparation of small arteries was
      beneficial compared with blunt preparation.

PMID- 9641275
TI  - Treatment of osteonecrosis of the femoral head with free vascularized fibular
      transfer.
AB  - Thirty-one free vascularized fibular bone grafts were performed for treatment of
      osteonecrosis of the femoral head in 26 patients. Twenty-four men and 2 women
      ranged in age from 16 to 48 years (mean, 32 years). Twenty-one patients had
      unilateral disease. Five patients had bilateral disease and underwent staged
      bilateral free vascularized fibular grafts 3 months apart. Associated etiological
      factors included alcohol (9 patients), steroid use (7 patients), and trauma (1
      patient). The condition was considered idiopathic in the remaining 9 patients.
      Radiological staging by Ficat included stage I in 1 hip, stage II in 15 hips,
      stage III in 14 hips, and stage IV in 1 hip. A skin island flap was used for
      monitoring purposes to check the patency of blood flow to the grafted fibula. One
      flap failed by venous occlusion and was left as a nonvascularized bone graft.
      Thirty hips were followed. Pain was relieved in 28 hips (93.3%) and aggravated in
      2 hips (6.7%). On radiographic evaluation, 26 hips (86.7%) demonstrated excellent
      preservation of the femoral head contour. Progressive collapse of the femoral
      head (>1-2 mm) occurred in two hips, with 1-mm depression in one hip with stage
      III disease and 2-mm collapse in one hip with stage IV disease. Follow-up ranged
      from 12 to 40 months (mean, 21 months). In conclusion, even in this relatively
      short follow-up period, the free vascularized fibular bone graft is an excellent
      treatment modality for preserving the femoral head and relieving symptoms in
      patients with osteonecrosis of the femoral head.

PMID- 9641276
TI  - Immediate free flap reconstruction for head and neck pediatric malignancies.
AB  - We performed six immediate free flap reconstructions after tumor ablation in 5
      children under the age of 15 years presenting with head and neck malignancy. One
      patient underwent free flap transfer on two separate occasions because of tumor
      recurrence. There were no flap losses nor were there any complications related to
      microvascular surgery. Although a pediatric head and neck malignant tumor is
      rare, surgical resection is the primary therapeutic role for those that are
      amenable to complete excision. Pediatric microsurgery provides a safe and
      reliable procedure for reconstruction of head and neck defects after extirpation
      of the tumor.

PMID- 9641277
TI  - Further experience with upper lip flaps for reconstruction of the ala nasi and
      alar base defects.
AB  - Reconstruction of the ala nasi and the alar base presents problems because of
      complex contours, skin color and texture, and limited availability of mobile,
      adjacent skin. A large percentage of basal cell carcinomas occur on the nose.
      When excised with adequate safety margins, these lesions create a defect too
      large for direct repair. This paper describes the use of the upper lip flap for
      reconstructing alar base defects and reconstructing the inner lining of the ala
      nasi in full-thickness defects of the ala nasi as an alternative to other
      procedures proved to be effective on this region. The base of the flap rests on
      the base of the columella. It is raised just over the underlying orbicularis oris
      muscle. The resulting donor defect is closed primarily. The outer aspect of
      defects of the ala nasi are covered with either a full-thickness skin graft, a
      forehead flap, or a cheek flap. The upper lip flap was used on 10 patients to
      reconstruct full-thickness defects of the ala nasi, for which an alar base needed
      to be reconstructed. The results were satisfactory in most patients. An upper lip
      flap can be used safely to reconstruct the ala nasi and alar base defects either
      alone or in combination with other flaps.

PMID- 9641278
TI  - The effect of the suture-induced delay phenomenon on skin flap survival and lipid
      peroxidation in rats.
AB  - Skin flap ischemia has been associated with the presence of free radicals. In
      this study we designed a suture-induced delay model in 30 rats using two
      different suture techniques. A total of 13 rats that underwent McFarlane's acute
      random-flap model served as controls. We found a statistically significant
      difference between the flaps of the experimental and control groups regarding the
      viability of flaps. Malondialdehyde levels in tissue samples taken from the
      proximal and distal ends of each flap were estimated at 6 and 24 hours
      postoperatively. Malondialdehyde levels in the experimental groups were found to
      be quite lower than those of the controls. In conclusion, the suture-induced
      delay model seems to be effective in improving flap viability. Also, we found
      lower malondialdehyde levels in experimental groups compared with controls.

PMID- 9641279
TI  - Ischemia/reperfusion injury in flow-through venous flaps.
AB  - The effects of ischemia/reperfusion (I/R) injury in flow-through venous flaps
      were evaluated in rabbits. The rates of flap survival and the levels of lipid
      peroxidation, protein oxidation, and sulfhydryl groups were compared between flow
      through venous flaps, conventional flaps after an I/R period (experimental
      groups), and flow-through venous flaps without being subjected to I/R injury
      (control groups) in 20 animals. On the seventh day after the onset of
      reperfusion, 3 of 10 flow-through venous flaps (30%) and 6 of 10 arteriovenous
      flaps (60%) survived in the experimental groups. Flow-through venous flaps showed
      a decreased survival rate compared with control and conventional flaps (p <
      0.05). Tissue lipid peroxide levels were found to be higher in venous flaps
      during reperfusion after secondary ischemia (p < 0.05). Tissue protein oxidation
      and total sulfhydryl groups levels did not show any difference among groups. This
      study suggests that more free radical damage occurs in flow-through venous flaps
      during I/R injury.

PMID- 9641280
TI  - The influence of ischemia/reperfusion injury on the jejunum.
AB  - Ischemia/reperfusion injury (IRI) after free tissue transfer of the small
      intestine results in transmural tissue damage. This study examined the effects of
      IRI on the jejunum. Wistar rats served either as controls (N=10) or underwent
      clamping of the infrarenal aorta for 1 hour followed by 1 hour of reperfusion
      (N=10). Both ischemia and reperfusion reduced the protein and deoxyribonucleic
      acid content of the jejunal mucosa (p < 0.05). Myeloperoxidase activity in the
      jejunal mucosa remained relatively low. The expression of leukocyte function
      associated antigen 1 and intercellular adhesion molecule 1 (ICAM-1) on the
      surface of mucosal cells was not altered significantly by the ischemic insult,
      but was reduced after the period of reperfusion (p < 0.05). This coincided with
      an increase in messenger ribonucleic acid (mRNA) for ICAM-1 within isolated
      mucosal cells (p < 0.05). The specific activity of glutaminase in isolated
      jejunal mucosal cells was diminished after ischemia and reperfusion (p < 0.05),
      and this was not associated with an appreciable change in glutaminase mRNA
      expression. These results have identified some molecular mechanisms underlying
      IRI of the small intestine that are possible candidates for therapeutic
      intervention.

PMID- 9641281
TI  - A temporal analysis of the effects of pressurized oxygen (HBO) on the pH of
      amputated muscle tissue.
AB  - The effect of hyperbaric oxygen (HBO) on ischemic muscle tissue pH was evaluated
      continuously. The hind limbs of male Sprague-Dawley rats (N=11, both groups) were
      amputated and stored in room air (20.1% oxygen [O2], 1.0 ATM, 24 degrees C) or in
      HBO (100% O2, 2.9 ATM, 24 degrees C) for 240 minutes. Rat muscle tissue pH was
      continuously monitored with a micro-pH electrode following amputation. There was
      no significant difference between the average starting tissue pH of control and
      treated limbs (p=0.45). At 240 minutes of ischemia the control group tissue pH
      decreased 0.80 pH units whereas the treatment group decreased 0.68 pH units (p <
      0.05). The tissue pH of control limbs declined 30.7 times faster than treated
      limbs during the first 36 minutes of ischemia (p < 0.05). From 36 to 240 minutes
      the rates of acidosis were similar and did not differ significantly (p=0.46). In
      a separate study, male Sprague-Dawley rats were anesthetized with pentobarbital
      and ketamine. Aortic arterial blood gases were obtained at 5 minutes (N=8) and 15
      minutes (N=8) postanesthesia. The average serum pH, carbon dioxide, oxygen, and
      bicarbonate levels remained within normal limits in both groups and did not
      differ significantly (p > 0.05 for all parameters). Anesthesia produced no serum
      respiratory or metabolic acidosis and did not contribute to the initial ischemic
      tissue pH. These results suggest that HBO delays the progression of metabolic
      acidosis in this amputated limb model. This is further supporting evidence for
      the tissue-preserving effect of oxygen when delivered in hyperbaric conditions.
      However, the clinical application of this technique may be limited due to the
      difference in the volume of tissue presented for major limb replantation and the
      short window of beneficial effects.

PMID- 9641282
TI  - The impact of vasodilators on random-pattern skin flap survival in the rat
      following mainstream smoke exposure.
AB  - This study demonstrates that acute mainstream cigarette smoke exposure is
      deleterious to dorsal random-pattern skin flap survival in the rat. Three
      vasodilators were also studied for their ability to mediate flap survival after
      smoke exposure. Sprague-Dawley rats (10 per group) were exposed to two cigarettes
      per day over a 14-day period. This is an exposure equivalent to that of an
      average cigarette smoker. Dorsal McFarlane caudally based random-pattern skin
      flaps (4 x 10 cm) were created on day 7 of the smoke exposure. Enteral
      phenoxybenzamine (0.56 mg per kilogram per day), enteral nifedipine (10 mg per
      kilogram per day), and topical nitroglycerin (1.3 cm or 7.5 mg per day) were
      administered after creation of the dorsal skin flaps in two doses daily during
      smoke exposure. Fluorescein was used to delineate areas of viability accurately.
      A pad digitizer was utilized to calculate designated skin flap areas to +/-1.0
      mm2. Experimental animals demonstrated a 23% decrease (p < 0.01) in skin flap
      area survival compared with the control animals. The phenoxybenzamine group
      demonstrated a 5.5% increase in flap area survival (p=0.068), the nifedipine
      group demonstrated a 4.1% increase in flap area survival (p=0.049), and the
      nitroglycerin group demonstrated an 8.9% increase in flap area survival
      (p=0.049). These data suggest that phenoxybenzamine appears to affect skin flap
      survival marginally after smoke exposure. However, nifedipine and nitroglycerin
      improve random-pattern skin flap survival significantly after mainstream
      cigarette smoke exposure in the rat. These results imply that pharmacological
      intervention with vasodilators may ultimately prove clinically useful for random
      pattern skin flap salvage in the cigarette-smoking patient.

PMID- 9641283
TI  - Salvage treatment for sarcomas of the hand.
AB  - We report 6 patients (1 male and 5 females; age range, 13-77 years) with hand
      sarcoma. The lesions were located between the digits and the distal end of the
      radius. A painless mass was the common manifestation in these patients. An
      incisional biopsy was performed on every patient, and histology revealed two low
      grade malignant sarcomas and four high-grade malignancies. A surgical salvage
      procedure was performed. The 4 patients with high-grade malignancy underwent
      adjuvant therapy such as radiotherapy and/or chemotherapy. Four patients are
      still alive and exhibit acceptable function in the affected hand. Our surgical
      procedure is presented.

PMID- 9641284
TI  - The granulometer--a pocket scale for the assessment of wound healing.
AB  - In spite of the availability of high-tech devices for wound assessment, plastic
      surgeons recognize that the color and confluence of granulation tissue are the
      most important indicators of open-wound healing. We developed a simple and
      inexpensive pocket-size scale--the Granulometer--to facilitate a finer assessment
      and to standardize the documentation of wound healing. This device overcomes
      limitations set by conditions such as lighting or recent exposure to other wounds
      that could distort the examiner's perception of the wound in question. In this
      study we examined the inter- and intraobserver variations in judgment, and the
      validity of the Granulometer. Our results demonstrate that skin graft viability
      can be predicted accurately by this eight-grade scale. Since graft survival
      depends on proper wound healing, we believe that the Granulometer can also be
      used for fine assessment of wound treatment. The low inter- and intraobserver
      variations indicate that the Granulometer measurements are both reproducible and
      accurate.

PMID- 9641285
TI  - Endoscopic management of subcutaneous gunshot wound with irrigation technique.
AB  - The application of the endoscope to the treatment of gunshot wounds has never
      been reported to our knowledge, with the exception of the laparoscope and the
      sigmoidscope in abdominal gunshot wounds. We report a patient with a subcutaneous
      gunshot wound who was treated endoscopically using the irrigation technique. The
      patient was a 25-year-old man who had been shot in the upper arm. The bullet was
      found near the thoracic spine via radiograph. At surgery the endoscope was
      inserted into the wound and irrigation was started. Excellent views could be
      obtained by irrigation, and the endoscope was advanced along the path of the
      bullet. The bullet and several fragments were removed with two additional small
      incisions. The method described herein seems beneficial in that (1) it is less
      invasive than conventional surgical debridement with a long incision, (2) it may
      provide information helpful in diagnosing the condition and the location of the
      bullet and its path, and (3) saline irrigation may have a cleansing effect.

PMID- 9641286
TI  - Endoscopic osteosynthesis for frontal bone fracture.
AB  - Endoscopic surgery to repair a frontal bone fracture is described. This operation
      is less invasive than the conventional open technique, which is performed under
      direct vision through a bicoronal or eyebrow incision. Endoscopic surgery leaves
      no conspicuous scars in the forehead and is free from complications such as nerve
      or vascular injuries, and appears to be of significant clinical value.

PMID- 9641287
TI  - Intercostal thorascopic harvesting of the internal mammary artery for
      supercharging a pedicled rectus abdominis flap.
AB  - Thorascopic harvesting of the internal mammary artery for supercharging the
      rectus abdominis pedicled flap for breast reconstruction is presented. The
      procedure was carried on a woman who had previously undergone a mastectomy and
      who was obese and a diabetic. The patient underwent a "high" flap delay 2 weeks
      earlier. At the time of operative transfer and setting, the flap's vascularity
      was found to be compromised. Instead of turbocharging the deep inferior
      epigastric pedicle to the irradiated axillary vessels, it was possible to harvest
      and utilize the internal mammary artery without rib resection for the
      supercharging, thus saving the flap and reconstruction. The technical aspects,
      and possible advantages and disadvantages of such a procedure are discussed.

PMID- 9641288
TI  - Use of the umbilicus in reconstruction of the vulva and vagina with a rectus
      abdominis musculocutaneous flap.
AB  - Flap reconstruction of the vulva and vagina following gynecological ablative
      procedures has become an integral part of the management of gynecological
      oncology patients. The benefits of flap reconstruction, including early primary
      healing, improved cosmesis over skin grafting, and prolonged secondary wound
      healing, have been well accepted. Additionally, the creation of a neovagina or
      neovulva often restores the sexual function and positive body image of the
      patient lost to radical procedures. The gracilis musculocutaneous flap has been
      used extensively in flap reconstruction but reports of partial flap necrosis and
      the need for extensive dissection of both thighs have led to alternative flap
      choices. The rectus musculocutaneous flap, with its hardier cutaneous blood
      supply, is often too bulky and difficult to inset delicately around the preserved
      urethral and vaginal cuff. The umbilicus has the required soft tissue, and its
      conically contoured depression allows for delicate insetting of the rectus
      abdominis musculocutaneous flap around the urethral cuff. We present 2 patients
      who underwent vertical rectus musculocutaneous flaps with umbilical soft tissue
      to restore urinary function and to create a cosmetic nonfunctional vagina.

PMID- 9641289
TI  - Inverted deepithelialized latissimus dorsi flap for the correction of lumpectomy
      defects in the irradiated breast.
AB  - Deformities following lumpectomy and radiation can provide reconstructive
      challenges for the plastic surgeon. With the increasing incidence of breast
      conservation therapy, these problems are likely to become more frequent in the
      future. The use of autologous tissue, particularly the latissimus dorsi, provides
      an excellent option for correcting these tissue deformities. We propose using an
      inverted latissimus with a deepithelialized skin paddle to correct these defects
      when there is no shortage of overlying skin. Additionally, this technique
      provides a softer texture to the entire radiated breast.

PMID- 9641290
TI  - Aneurysms of the superficial temporal artery: literature review and case reports.
AB  - Superficial temporal artery (STA) aneurysms are a medical rarity. There are less
      than 200 patients reported in the literature. The majority of cases are of
      traumatic etiology and occur in young men. The senior authors reported a case of
      STA aneurysm in 1978. We now review the literature and report on three additional
      patients with STA aneurysm and a fourth patient with a temporal lipoma that was
      diagnosed initially as an aneurysm. This is the first report of a preoperative
      diagnosis of STA aneurysm that subsequently proved incorrect.

PMID- 9641291
TI  - Endometrioma of the abdominal wall following combined abdominoplasty and
      hysterectomy: case report and review of the literature.
AB  - An unusual case is reported of abdominal wall endometrioma presenting in a lower
      abdominal scar following a combined hysterectomy and abdominoplasty performed 5
      years earlier. Current diagnostic methods and recommended surgical management are
      outlined.

PMID- 9641292
TI  - Muir-Torre syndrome.
AB  - Muir-Torre syndrome is a rare autosomal dominant disorder characterized by
      unusual sebaceous neoplasms and visceral malignancy. Excluding sebaceous
      hyperplasia and sebaceous nevus of Jadassohn, sebaceous neoplasms occur so rarely
      that the presence of a sebaceous neoplasm mandates consideration of Muir-Torre
      syndrome. Sebaceous neoplasms precede or are synchronous with visceral
      malignancies in up to 40% or more of patients with Muir-Torre syndrome, and the
      presence of such a lesion warrants an evaluation for visceral malignancy.

PMID- 9641293
TI  - Gynecomastia of the male nipple.
AB  - Diseases of the male nipple can be responsible for severe problems for the
      patient. The location of gynecomastia can be restricted to the nipple. Carcinoma
      should also be considered. The therapy of choice is operative treatment. A subtle
      microsurgical procedure is helpful to achieve a good functional and cosmetic
      result.

PMID- 9641294
TI  - Residency training: how long and by what method?

PMID- 9641295
TI  - Management guidelines for uninvestigated and functional dyspepsia in the Asia
      Pacific region: First Asian Pacific Working Party on Functional Dyspepsia.
AB  - Dyspepsia is most optimally defined as pain or discomfort centred in the upper
      abdomen. The symptom complex may be caused by peptic ulcer disease, gastro
      oesophageal reflux, or gastric cancer but is most often due to functional (or non
      ulcer) dyspepsia. While upper endoscopy is the method of choice to determine the
      underlying cause of dyspepsia, it is expensive. A more pragmatic approach is
      needed in the Asia Pacific region where health services are limited. A detailed
      treatment algorithm is given for managing patients presenting with new-onset
      dyspepsia and documented functional dyspepsia after endoscopy, and evidence to
      support this approach is reviewed. Prompt endoscopy is recommended for patients
      with alarm features. In patients without alarm features, treatment for 2-4 weeks
      with an empirical anti-secretory or prokinetic agent, followed by investigation
      using non-invasive Helicobacter pylori testing and treatment for patients who do
      not respond or relapse, is recommended. Trials of management strategies are now
      needed to establish the efficacy and cost-effectiveness of the approaches
      recommended.

PMID- 9641296
TI  - Infection, sepsis and systemic inflammatory response syndrome in obstructive
      jaundice.

PMID- 9641297
TI  - Rising incidence of oesophageal adenocarcinoma in men in Australia.
AB  - Adenocarcinomas of the oesophagus and of the gastric cardia have been reported to
      be increasing in incidence in many countries, while the incidence of squamous
      cell carcinoma of the oesophagus is stable and non-cardia gastric cancers are
      decreasing in incidence. Age-standardized incidence rates for the years 1982-1993
      for oesophageal adenocarcinoma and non-adenocarcinoma, and gastric cardia and non
      cardia cancers were calculated based on state cancer registry incidence data.
      Time trends in the age-standardized rates were assessed using linear regression.
      A consistent increasing trend in the incidence of oesophageal adenocarcinoma in
      men was seen in all states of Australia and was statistically significant in all
      states except South Australia. There were no consistent nationwide trends in the
      incidence of oesophageal adenocarcinoma in women, although a trend towards an
      increase in the incidence of this cancer reached statistical significance (P <
      0.05) in three states (New South Wales, Victoria, Queensland). There were no
      important trends in the incidence of oesophageal non-adenocarcinoma in either men
      or women. There were no consistent nationwide changes in the incidence of gastric
      cardia cancer in either men or women, although this cancer was significantly
      increasing in Tasmania in both men and women. The incidence of cancer of the
      stomach not arising at the gastric cardia was significantly decreasing in men in
      all states and was also decreasing in women in all states, although in women this
      decrease was statistically significant only in New South Wales, Victoria and
      Western Australia. There has been a dramatic increase in the incidence of
      oesophageal adenocarcinoma in men in Australia. The incidence of this cancer in
      men is now approximately equal with that of non-adenocarcinoma of the oesophagus.
      The incidence of non-cardia stomach cancer continues to fall.

PMID- 9641298
TI  - Oral human spasmolytic polypeptide protects against aspirin-induced gastric
      injury in rats.
AB  - Spasmolytic polypeptide (SP) is a member of the trefoil peptide family; gut
      peptides that participate in the protection and repair of the gastric mucosa.
      Previous studies have failed to agree on the mode of action of human SP (hSP). We
      investigated the effect of orally administered human SP on the protection and
      repair of rat gastric mucosa in an established in vivo model of damage induced by
      the non-steroidal anti-inflammatory drug aspirin (ASA). The integrity of the
      gastric mucosa was quantified in four ways: the temporal change in transmucosal
      potential difference (PD), area of macroscopic damage by planimetry, relative
      area of microscopic damage by histological morphometry, and the number of deep
      erosions per centimetre of mucosa sectioned. Human SP (200 micromol/L)
      administered orally before, or in combination with ASA significantly reduced the
      fall in PD, the area of microscopic damage, and the number of deep erosions (P <
      0.05). The area of macroscopic damage was significantly reduced only in rats
      where hSP (200 micromol/L) was given in conjunction with ASA (P < 0.05). Human
      spasmolytic polypeptide (70 or 200 micromol/L) administered after ASA failed to
      hasten the re-establishment of PD or stimulate the repair of the gastric mucosa
      in the 90 min following injury (P > 0.05, compared with ASA alone). We conclude
      that hSP prevents gastric mucosal damage by its topical actions, probably by a
      rapid interaction with luminal mucins or epithelial cells, but fails to stimulate
      early restitution in the injured gastric mucosa.

PMID- 9641299
TI  - Percutaneous endoscopic gastrostomy feeding in AIDS.
AB  - Reduced energy intake is the most important reason for weight loss in advanced
      human immunodeficiency virus (HIV) infection. From January 1989 to August 1995
      enteral feeding via a percutaneous endoscopic gastrostomy tube (PEG) was offered
      to all human immunodeficiency virus(HIV)/AIDS patients attending Fairfield
      Hospital, Melbourne who were unable to maintain 85% ideal body weight. A total of
      71 patients received enteral feeding (1000-2000 kcal/day) for a median period of
      161 days (range 4-644 days). Fifty-one (72%) patients gained 5.8 +/- 4.4kg (range
      0.4-19.2 kg). Nine gained 10 kg or more. The median time to maximum weight was 74
      days after PEG insertion. Those who gained weight had a longer median survival,
      but this difference was not statistically significant (210 vs 109 days, P =
      0.07). The only predictor of weight gain was a CD4 count greater than 100/microL.
      Patients who gained weight reported improved quality of life and increased
      independence. However, early complications, especially wound infection, were
      common. Although these data have been gathered retrospectively, our experience
      suggests that enteral feeding can maintain or improve nutritional status and may
      improve quality of life in advanced HIV infection.

PMID- 9641300
TI  - Flow cytometric analysis of cell proliferation kinetics during duodenal ulcer
      healing.
AB  - Cell proliferation in the gastroduodenal mucosa of patients with duodenal ulcers
      was evaluated using flow cytometry. Forty patients with duodenal ulcers and 12
      normal subjects were investigated. Biopsy samples were obtained during endoscopic
      examination and subjected to DNA analysis by flow cytometry. Thirty patients with
      duodenal ulcers were healed within 3 months with H2 blockers (tractable or
      responsive ulcers), whereas 10 patients did not respond to treatment (intractable
      ulcers). The percentage of cells at the DNA-synthetic phase, an index of cell
      proliferation, was constant in the adjacent duodenal mucosa 2 cm from ulcer
      margin and antral mucosa during duodenal ulcer healing. The index at the margin
      of tractable ulcers was elevated during the active stage (12.9 +/- 1.3), peaked
      during the healing stage (15.4 +/- 2.8) and returned to the same level at the
      scarring stage (10.9 +/- 2.0) as normal controls (10.3 +/- 1.7). However, the
      index was not elevated in intractable ulcers (10.3 +/- 1.7 in the healing stage)
      and was smaller than in tractable ulcers. These data indicate that augmented
      mucosal cell proliferation at the ulcer margin plays an important role in
      duodenal ulcer healing and intractable ulcers are characterized by an abnormal
      failure to accelerate DNA synthesis to achieve ulcer repair.

PMID- 9641301
TI  - Case report: Spontaneous isolated mesenteric fibromatosis presenting as
      megaduodenum.
AB  - A case of spontaneous isolated mesenteric fibromatosis presenting as megaduodenum
      is reported. The lesion was small, only 2 cm in its greatest diameter. However,
      because of its location near the ligament of Treitz and because of its
      characteristic infiltrative growth pattern, the tumour involved the distal
      duodenum and resulted in acute angulation and obstruction early in its course. We
      successfully resected the mass and the patient is in fair physical condition 6
      months after operation.

PMID- 9641302
TI  - Case report: Haemangioma of the small intestine complicated by protein-losing
      gastroenteropathy.
AB  - We report a case of haemangioma of the small intestine complicated by protein
      losing gastroenteropathy. A 32-year-old female had suffered from hypoproteinaemia
      for 6 years, but the cause of this condition had not been determined. On
      diagnosis and therapy for hypoproteinaemia, intra-operative endoscopy and
      histological examination were performed and she was subsequently diagnosed with
      capillary haemangioma of the small intestine. Angiography was not useful for the
      detection of capillary haemangioma of the small intestine in this case. Although
      intestinal haemangioma is an important cause of gastrointestinal bleeding,
      protein loss is an extremely rare complication and this case is the first to be
      reported in Japan.

PMID- 9641303
TI  - Greatly increased mucosal nitric oxide in ulcerative colitis determined in situ
      by a novel nitric oxide-selective microelectrode.
AB  - Although current nitric oxide (NO) electrodes are simple, selective and
      sensitive, they are fragile and hard to use in clinical studies of patients. By
      preparing an improved NO electroneedle that overcomes these defects, we directly
      measured mucosal NO concentrations in 11 patients (six male, five female; mean
      26.0 years old) with ulcerative colitis (UC) and five normal volunteers (three
      male, two female; mean 28.3 years old) in situ. An electroneedle was inserted
      into colonic mucosa through a biopsy channel during colonoscopy. The information
      concerning the concentration of NO generated and the appearances of the colonic
      mucosa at the same site were obtained simultaneously. In the ulcerative colitis
      patients, NO concentrations were significantly increased at all 24 mucosal sites
      tested. These included sites where: there was an absence of visible inflammation
      (five sites); the mucosa was mildly inflamed (eight sites); the mucosa was
      moderately inflamed (five sites); or severely inflamed (six sites). The NO
      concentrations in ulcerative colitis patients were 12-72 times higher than the NO
      levels in normal controls (10 sites). At the same 10 sites in four ulcerative
      colitis patients, the high NO concentrations were decreased by 53% after
      glucocorticoid treatment. These data are consistent with those of previous
      studies utilizing different NO electrodes. Excess mucosal NO is generated from
      inducible NO synthase in the inflamed mucosa itself and the invading inflammatory
      cells. Our results suggested that mucosal NO could be a marker for the extent of
      inflammation and its various actions correlated with the pathogenesis, natural
      history and prognosis of UC. Using the NO microelectrode system reported here,
      the concentration of NO generated can be monitored in real-time while observing
      the mucosal condition at the same site during endoscopy. This novel NO electrode
      may contribute to understanding the role of NO in colonic mucosal inflammation.

PMID- 9641304
TI  - A study of laboratory based faecal occult blood testing in Melbourne, Australia.
      The Faecal Occult Blood Testing Study Group.
AB  - Faecal occult blood tests (FOBT) are widely used in clinical practice and are
      under increasing scrutiny as a tool for colorectal cancer screening. However,
      there is little information regarding the quality of testing performed in
      pathology laboratories. Therefore, we asked 13 pathology laboratories in
      Melbourne, Australia, to test coded contrived faecal samples prepared from a
      composite stool specimen which had been spiked to various concentrations of
      haemoglobin. The samples were provided to the laboratories in two forms: (i)
      on/in the sample collection device appropriate for the faecal occult blood test
      they normally used; and (ii) as a moist faecal sample. Some variation in
      threshold analytical sensitivity between laboratories for the same FOBT was
      observed for Hemoccult SENSA, ColoRectal, Hematest, MonoHaem and Hemolex
      suggesting that, at least for those tests, technician training could be improved.
      Two tests, Hematest and an in-house FOBT did not perform as well as the other
      FOBT. When samples were sent in moist form, Hemoccult SENSA (P = 0.0002),
      ColoRectal (P = 0.02) and MonoHaem (P = 0.04) had significantly lower overall
      positivity rates; for Hemolex the decrease was not significant (P = 0.3). The
      lower positivity rate with moist samples is important, given that 11 of the 13
      laboratories in the study stated that they receive at least some samples in moist
      form. Thus, technician training and laboratory procedure need to be reviewed to
      maximize the benefits of faecal occult blood testing in clinical practice,
      especially with its expanding role in colorectal cancer screening.

PMID- 9641305
TI  - Case report: an inherited APC mutation in the first reported Australian case of
      Turcot's syndrome.
AB  - The objective of this study was to determine the inherited gene mutation
      responsible for the first reported Australian case of Turcot's syndrome. DNA was
      extracted from the archival tissue blocks obtained at the time of the patient's
      original surgery and from fresh blood samples obtained from selected family
      members. These were analysed for mutations of the familial adenomatous polyposis
      gene (APC). Analysis of DNA from the archival blocks and from each of the
      affected family members revealed an inherited 5 base pair deletion at codon 1061
      of APC. In this case, the central nervous system tumour represents an
      extracolonic manifestation of familial adenomatous polyposis. The underlying
      inherited mutation of APC has been identified. In some cases of Turcot's
      syndrome, other genes appear to be involved. Recent literature examining the
      molecular basis of Turcot's syndrome is reviewed.

PMID- 9641306
TI  - Effect of obstructive jaundice on neutrophil chemotactic activity: an in vivo
      assessment in zymosan-induced peritonitis model in rats.
AB  - The effect of obstructive jaundice on local neutrophil accumulation in response
      to inflammatory stimulus was investigated in rats. Obstructive jaundice was
      produced by bile duct ligation for 7 days. Zymosan (200 mg) was injected
      intraperitoneally and 4h later myeloperoxidase activity in the peritoneal fluid
      was measured to quantify neutrophil recruitment. Zymosan-induced neutrophil
      recruitment was significantly greater (more than two-fold) in bile duct-ligated
      rats than in sham-ligated or normal animals. Depletion of peritoneal cells
      significantly suppressed neutrophil recruitment after zymosan injection in all
      three groups, with no significant differences between the groups. In normal rats,
      replacement of their peritoneal cells by those from bile duct-ligated rats did
      not enhance zymosan-induced neutrophil recruitment. In contrast, bile duct
      ligated rats treated with peritoneal cell replacement from normals showed
      significantly increased neutrophil recruitment after zymosan injection. In vitro
      neutrophil chemotaxis in response to formyl-Met-Leu-Phe was significantly
      enhanced in bile duct-ligated rats, compared with that in sham-ligated animals.
      The results suggest that local neutrophil recruitment in response to inflammation
      may be enhanced in obstructive jaundice and that increased neutrophil chemotactic
      activity, not macrophage activity, may play a prime role in the mechanism.

PMID- 9641307
TI  - Predictive factors in eradicating hepatitis C virus using a relatively small dose
      of interferon.
AB  - Interferon (IFN) can reduce hepatitis C virus load and even eliminate the virus
      in 30-40% of patients. Several predictive factors for eradication of the virus
      have been reported and a higher dose of IFN tends to result in elimination of the
      virus. However, a small dose of IFN sometimes is as effective as a large dose in
      eradicating the virus. The predictive factors for such a response are not well
      established. We retrospectively analysed 50 patients with chronic hepatitis C who
      were treated with relatively small amounts of IFN (equal or less than 252 million
      units). Eleven patients were responders (elimination of hepatitis C virus (HCV)
      and normalization of alanine amino transferase (ALT) for at least 6 months), but
      the remaining 39 were non-responders. Multivariate analysis showed that the
      pretreatment viral load and total dose of IFN per kilogram of bodyweight were
      significant predictive factors of response to therapy. We also assessed the amino
      acid substitutions in the IFN sensitivity determining region (ISDR), NS5A codon
      2209-2248, of HCV in serum samples obtained from 31 patients with HCV genotype
      1b. The presence of more than one amino acid substitution in the ISDR tended to
      correlate with HCV genotype 1b elimination. As IFN is expensive and has a number
      of serious side effects, our study suggests that the optimal dose of IFN may vary
      from one patient to another and that more stringent criteria should be used to
      select the optimal dose for therapy.

PMID- 9641308
TI  - How much does alcohol contribute to the variability of hepatic fibrosis in
      chronic hepatitis C?
AB  - In order to determine the contribution of alcohol intake to the severity of
      hepatic fibrosis in patients with chronic hepatitis C, we studied associations
      between various levels of alcohol intake, other demographic variables and
      semiquantitative liver histology in 434 cases of chronic hepatitis C. Clinical,
      demographic and disease-related data were entered into a relational database.
      Liver histology was scored according to Scheuer. The average daily alcohol intake
      for the year preceding liver biopsy (recent exposure) and for earlier periods
      (past exposure) was categorized into five levels of intake. One-third of patients
      gave a history of alcohol intake that had exceeded 40 g/day for at least 5 years.
      By univariate analysis, age, but not recent or past alcohol intake or other
      baseline variables, was associated with portal score (r = 0.14, P = 0.004),
      fibrosis score (r = 0.46, P < 0.001), total Scheuer score (r = 0.35, P < 0.001).
      However, by multivariate analysis, age (P < 0.001), past (but not present)
      alcohol intake (P < 0.001) and birth in Egypt (P = 0.006) were independently
      associated with fibrosis score. Age, past alcohol and birth place in Egypt
      contributed 27% to total variance of the hepatic fibrosis score, while age alone
      accounted for 23%. Age also independently predicted portal activity (P = 0.02)
      and total Scheuer score (P < 0.001), whereas past alcohol intake correlated with
      total Scheuer score (P = 0.002) but not with other histological indices. A
      separate multivariate analysis was performed on a more homogeneous subgroup of
      196 patients who acquired hepatitis C by injection drug use. In this subgroup,
      age (P < 0.05) and past alcohol (P < 0.05) were independently associated with
      fibrosis score. In both the overall and subgroup analyses, there was a threshold
      level of past alcohol intake (>80 g/day) beyond which the risk of fibrosis
      increased significantly. It is concluded that toxic levels of alcohol exposure
      for at least 5 years accentuate hepatic fibrosis in hepatitis C but the influence
      of alcohol appears to be minor compared with age and other variables and is
      exerted only at toxic levels of intake.

PMID- 9641309
TI  - Effects of colchicine and phenothiazine on biliary excretion of organic anions in
      rats.
AB  - Vesicular transport inhibitors have been reported to inhibit biliary excretion of
      some organic anions, suggesting that vesicular transport has a role in
      intracellular transport of these compounds. However, these inhibitors are
      substrates for P-glycoprotein. To examine whether P-glycoprotein has a role in
      canalicular transport of organic anions in addition to the canalicular
      multispecific organic anion transporter, we studied the effect of colchicine, a
      vesicular transport inhibitor, and phenothiazine to increase P-glycoprotein
      expression on biliary excretion of various organic anions in rats. Colchicine
      treatment slightly but significantly inhibited biliary excretion of indocyanine
      green, dinitrophenyl-glutathione and pravastatin, and had no effect on biliary
      excretion of sulphobromophthalein and dibromosulphophthalein. Phenothiazine
      treatment did not affect biliary excretion of indocyanine green and pravastatin,
      but it increased biliary sulphobromophthalein-glutathione excretion. In
      conclusion, the present findings suggest that P-glycoprotein plays an additive
      role on biliary excretion of some organic anions in addition to the canalicular
      multispecific organic anion transporter.

PMID- 9641310
TI  - Hepatobiliary images. Pancreatic pseudocysts in the liver.

PMID- 9641311
TI  - Images in gastroenterology. Gastric antral vascular ectasia (watermelon stomach).

PMID- 9641312
TI  - The liver in traditional Chinese medicine.
AB  - Medical thinkers in China visualized the liver in microcosmal and macrocosmal
      terms. An anatomical tradition did not exist, hence the liver was described
      grossly in broad outline. It was recognized as being functionally important in
      the movement of qi (vital energy) and storage of xue ('blood'). The liver
      corresponded to various phenomena in both the natural and social orders,
      according to the scheme of yin yang and five phases. These interrelationships
      provided the basis for the diagnosis and treatment of liver dysfunctions. The
      disorders fell into three general groups: (i) hepatic qi stasis; (ii) hepatic
      yang excess with yin deficiency; and (iii) hepatic yin insufficiency. The signs
      and symptoms represented the logical outcomes of the disturbed physiology.
      Acupuncture, moxibustion and herbal drugs were used to redress the imbalance of
      hepatic qi and yin-yang. The impact of Western medicine led traditional authors
      to recognize the hepatobiliary role in bile secretion and in jaundice. The
      exchange between the Western and Chinese medical traditions revealed that active
      agents were included in the Chinese formulary, such as glycyrrhizin, which has
      recently been shown to be beneficial in chronic viral hepatitis.

PMID- 9641313
TI  - Current risks of viral hepatitis from blood transfusions.
AB  - The incidence of transfusion-associated hepatitis in the United States has fallen
      dramatically since the late 1960s. Where once the risks were so great that as
      many as one in three transfused patients contracted hepatitis, now they are
      infinitesimal. Many factors share responsibility for this accomplishment;
      however, two stand above the rest: (i) improved donor selection and screening
      criteria, especially elimination of paid blood donations; and (ii) major advances
      in testing for viral hepatitis carriers. Currently, four tests are used for the
      prevention of transfusion-associated hepatitis: (i) hepatitis B surface antigen;
      (ii) hepatitis C virus antibody; (iii) hepatitis B core antibody; and (iv)
      alanine aminotransferase. The first two tests are largely responsible for the
      current low risks of transfusion-associated hepatitis due to hepatitis B virus
      and hepatitis C virus of 1 in 63,000 and 1 in 125,000, per unit, respectively. To
      further reduce the risks of transfusion-associated hepatitis will require the
      enhanced sensitivity provided by nucleic acid amplification techniques (e.g.
      polymerase chain reaction). Currently, however, no such tests are licensed and
      practical, automated, or inexpensive enough for individual blood donor screening.
      We have made such great strides in the prevention of transfusion-transmitted
      hepatitis that background rates of viral hepatitis now greatly exceed the risk of
      transmission via transfusion. For this reason, while it may still be reasonable
      to consider a transfusion as a possible cause for hepatitis, it is imperative
      that many other possibilities (e.g., iatrogenic and other risk factors) be ruled
      out.

PMID- 9641314
TI  - Fluorescence imaging of Na+ influx via P2X receptors in cochlear hair cells.
AB  - The adenosine 5'-triphosphate (ATP)-activated membrane conductance, mediated by
      P2X receptors, was examined in isolated guinea-pig cochlear inner and outer hair
      cells. Photo-activated release of caged-ATP elicted a 30-ms latency inwardly
      rectifying non-selective cation conductance, blocked by the P2X receptor
      antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; 10-100
      microM), consistent with the direct activation of ATP-gated ion channels. A K(Ca)
      conductance in the inner hair cells (IHC), activated by the entry of Ca2+ through
      the ATP-gated ion channels, was blocked by including 10 mM 1,2-his(2
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) in the internal solution.
      Real-time confocal slit-scanning fluorescence imaging of Na+ influx through the
      ATP-gated ion channels was performed using the dye Sodium Green with simultaneous
      whole-cell recording of membrane currents. The Na+ entry was localized to the
      endolymphatic surface, with the increase in [Na+]i detected within approximately
      200 ms of the onset of the inward current response. Within 600 ms Na+ had
      diffused throughout the cell cytoplasm with the exception of the subnuclear
      region of the outer hair cells. Correlation of voltage-clamp measurements of Na+
      entry with regional increases in Na+-induced fluorescence demonstrated ATP
      induced increases in intracellular Na+ in excess of 45 mM within 4 s. These data
      provide direct evidence for the Na+ permeability of the ATP-gated ion channels as
      well as independent evidence for the localization of P2X receptors at the
      endolymphatic surface of the sensory hair cells. The localization of the ATP
      gated ion channels to the apical surface of the hair cells supports an ATP
      mediated modulation of 'silent' K+ current across the cochlear partition which
      could regulate hearing sensitivity by controlling the transcellular driving force
      for both mechanoelectrical and electromechanical transduction in hair cells.

PMID- 9641315
TI  - Estimating cochlear filter response properties from distortion product
      otoacoustic emission (DPOAE) phase delay measurements in normal hearing human
      adults.
AB  - This study examined cochlear filter response properties derived from f1- and f2
      sweep phase delay difference measures in 60 normal hearing human adults. Seven
      different f2 frequencies ranging from 1.1 to 9.2 kHz were presented (f2/f1 ratios
      of 1.1-1.3). F2 intensity level was varied in 5 dB steps from 30 to 50 dB SPL
      (the level of f1 was 15 dB above the level of f2). DPOAE delay estimates in a f2
      sweep paradigm are longer than in a f1-sweep paradigm at the same frequency and
      intensity. This indicates that the f2-sweep DPOAE phase delay is composed of a
      greater proportion of the filter response time at the site of DPOAE generation
      than the f1-sweep delay. This proportion was isolated by subtracting f1-sweep
      DPOAE delays from f2-sweep delays at similar f2 frequencies and intensities.
      Under the assumption of linearity and minimum phase the impulse response of the
      filter at each f2 stimulus level was calculated from the mean phase delay
      difference. Frequency response properties were calculated by Fourier
      transformation of the impulse response at each f2 frequency and intensity. High
      frequency low intensity impulse responses had longer response times and narrower
      frequency bandwidths than low frequency high intensity responses. The Q10dB
      values of DPOAE derived tuning curves ranged from 2.4 (1.5 kHz) to 7.3 (8.5 kHz).

PMID- 9641316
TI  - Genetics of age-related hearing loss in mice. IV. Cochlear pathology and hearing
      loss in 25 BXD recombinant inbred mouse strains.
AB  - The effects of three putative genes which contribute to age-related hearing loss
      (AHL genes) were evaluated using auditory brainstem response (ABR) thresholds and
      post-mortem cochlear histopathology in 25 recombinant BXD inbred mouse strains,
      originally derived from C57BL/6J (B6) and DBA/2J (D2) progenitor strains. All BXD
      strains showed substantial elevation of ABR thresholds and loss of spiral
      ganglion cells (SGCs) during the first year of life. The findings are consistent
      with our genetic model in which D2 and B6 inbred strains both possess the Ahl
      (age-related hearing loss) gene, whereas D2 possesses two additional chromosomal
      loci with AHL genes (Ahl2 and Ahl3). The between-strain distribution in the
      severity of SGC loss and ABR threshold elevations suggests that the severity of
      hearing loss is determined in large part by the number of AH L genes an animal
      possesses and by additional genetic background effects. The present findings also
      demonstrate that, because BXD strains vary substantially in the rate and severity
      of progressive hearing loss (but are genetically closely related), they can
      provide powerful animal models for developmental studies of AHL.

PMID- 9641317
TI  - Passive sound-localization ability of the big brown bat (Eptesicus fuscus).
AB  - The passive sound-localization ability (i.e. minimum audible angle) of the big
      brown bat, Eptesicus fuscus, was determined using a conditioned avoidance
      procedure in which the animals were trained to discriminate left sounds from
      right sounds. The mean threshold of three bats for a 100-ms broadband noise burst
      was 14 degrees, a value that is about average for mammals. A similar threshold of
      15 degrees was obtained for one animal when it was retested with one of its own
      recorded echolocation calls as the stimulus. The two bats tested on pure-tone
      localization were able to localize high-frequency, but not low-frequency tones,
      even when a low-frequency tone was amplitude modulated, a result indicating that
      these bats are not able to use binaural time-difference cues for localization.
      Finally, given the width of the bat's field of best vision, as determined by a
      count of its ganglion-cell density, its sound-localization acuity is consistent
      with the hypothesis that the role of passive sound localization is to direct the
      eyes to the source of a sound.

PMID- 9641318
TI  - Perceptual consequences of the interactions between spontaneous otoacoustic
      emissions and external tones. I. Monaural diplacusis and aftertones.
AB  - Research into monaural diplacusis has led to the concept of idiotones (tone-like
      stimuli of cochlea origin). Spontaneous otoacoustic emissions (SOAEs) are tone
      like stimuli generated by the cochlea and detected in the ear canal. In
      diplacusis, the existence of idiotones is inferred from disturbances of the
      perception of single tones. Spontaneous otoacoustic emissions are measured by
      placing a small microphone at the entrance to the ear canal. Many of the puzzling
      properties of the hypothesized idiotones are consistent with measurements of the
      interaction of SOAEs with external tones. The interactions of the SOAEs with
      external tones were analyzed acoustically. The perceptual properties evoked by
      250 ms pulses (presented twice a second) of the acoustic stimuli used in the OAE
      experiments were systematically investigated. At some stimulus levels, all
      subjects reported the perception of a second tone alternating with the external
      tone. The relative pitch of this percept was consistent with the frequency of the
      SOAE. The frequency dependence of the signal levels needed for the percept had
      many aspects in common with the suppression tuning curves of the SOAEs. At lower
      levels of the external tone the subjects sometimes reported a perception of two
      simultaneous tones. This would be consistent with the subject detecting SOAEs
      when they are frequency shifted, but not suppressed. The consumption of aspirin
      by one subject reduced the SOAE into the noise floor and eliminated the monaural
      diplacusis.

PMID- 9641319
TI  - Changes in cochlear blood flow due to intra-arterial infusions of angiotensin II
      (3-8) (angiotensin IV) in guinea pigs.
AB  - The effects of a newly discovered form of angiotensin, angiotensin IV (ANGIV), on
      cochlear blood flow (CBF) have been investigated utilizing the laser Doppler
      flowmetry (LDF) technique. Two specific questions were addressed: What are the
      effects of anterior inferior cerebellar artery infusions (AICA) of ANGIV on CBF
      and do angiotensin fragments other than ANGIV influence CBF in mature male and
      female guinea pigs. Infusions of ANGIV, and C-terminal shortened fragments were
      accomplished via micropipette into the AICA and changes in CBF were observed
      using LDF. The results demonstrated that 10 and 100 pmol/min doses of ANGIV
      increased CBF 22% and 75% (n = 6; P < 0.01) from baseline, respectively, with
      little change in mean arterial blood pressure (MAP). Pretreatment with the ANGIV
      antagonist divalanal-ANGIV (1 nmole/min) blocked increases in CBF due to
      infusions of 100 pmol/min of ANGIV. The infusion of the C-terminal shortened
      fragment ANGIV(1-5) and saline had no significant effect on either CBF or MAP.
      These results provide the evidence for a new subtype of the angiotensin receptor
      and indicate the likely role of circulating hormones in blood flow regulation in
      the inner ear.

PMID- 9641320
TI  - The dorsal cochlear nucleus contributes to a high intensity component of the
      acoustic startle reflex in rats.
AB  - The dorsal cochlear nucleus (DCN) has been shown to project to a region of the
      nucleus reticularis pontis caudalis (PnC) critical for the evocation of startle
      in rats, suggesting a possible modulatory influence of the DCN on startle. This
      study examined the involvement of the DCN in the acoustic startle reflex and
      various other forms of behavioral plasticity seen with this response. Animals
      received bilateral electrolytic lesions of the DCN and were tested for acoustic
      startle responses, background noise facilitation, short-term habituation,
      prepulse inhibition and facilitation, and fear conditioning. Compared to sham
      lesioned rats, DCN lesioned rats showed a significant reduction in startle
      amplitude at the two highest startle-eliciting intensities (110 and 115 dB SPL)
      and normal responses on all other measures. Hence, the DCN appears to contribute
      to a high intensity component of the acoustic startle response in rats.

PMID- 9641321
TI  - Intercellular junctional maturation in the stria vascularis: possible association
      with onset and rise of endocochlear potential.
AB  - The postnatal maturation of intercellular junctions of marginal and basal cells
      of the stria vascularis was examined in the gerbil using thin sections and freeze
      fracture techniques. Immunohistochemical methods were used to determine the
      presence of Na,K-ATPase postnatally. The onset and growth of endocochlear
      potential (EP) was also measured. In marginal cells, the apical surface and
      junctional region around the apical pole of the cell was found to have adult-like
      characteristics by the time of onset of EP, whilst the increase in staining for
      Na.K-ATPase temporally coincided with an increasing density of intra-membrane
      protein particles on the infoldings of marginal cell lateral membranes.
      Maturation of the junctional specialisations of the basal cells was found to
      correspond temporally with the period of onset and rise of EP. Tight junctions
      between basal cells first appeared as small, broken strands composed of widely
      spaced particles at 6 days after birth (DAB). These junctional strands increased
      in number and in particle density until adult-like at 16 DAB when they covered
      large areas of the basal cell lateral membrane. Gap junctions on the apical
      membrane of basal cells first appeared as small patches of loosely packed
      junctional elements at 6 DAB. Between 8 and 16 DAB the area of membrane occupied
      by the gap junctions increased, reaching a mature conformation by 18 DAB. The
      results suggest that EP maturation is dependent upon the development of sealing
      between the basal cells by tight junctions and also the establishment and
      development of gap junctions in the apical plasma membrane of basal cells,
      associated with intermediate cells.

PMID- 9641322
TI  - Ultrastructural localization of ChAT-like immunoreactivity in the human
      vestibular periphery.
AB  - Acetylcholine (ACh) has long been considered a neurotransmitter candidate in the
      efferent vestibular system of mammals. Recently, choline acetyltransferase
      (ChAT), the synthesizing enzyme for ACh, was immunocytochemically localized in
      all five end-organs of the rat vestibule (Kong et al. (1994) Hear. Res. 75, 192
      200). However, there is little information in the literature concerning the
      cholinergic innervation in the vestibular periphery of man. In the present study
      the ultrastructural localization of the ChAT-like immunoreactivity in the human
      vestibular periphery was investigated in order to reveal the cholinergic
      innervation in the human vestibular end-organs. A modified method of pre
      embedding immunoelectron microscopy was applied. It was found that the ChAT-like
      immunoreactivity was located in the bouton-type vesiculated nerve terminals in
      the vestibular neurosensory epithelia of man. These ChAT-like immunostained nerve
      terminals make synaptic contacts either with afferent chalices surrounding type I
      vestibular sensory hair cells, or with type II vestibular sensory hair cells.
      These results show that the ChAT-like immunoreactivity in the human vestibular
      periphery is confined to the efferent vestibular system. The ChAT-containing
      efferents innervate both type I hair cells and type II hair cells, making
      postsynaptic and presynaptic contacts, respectively. This study presents evidence
      that ACh is a neurotransmitter candidate in the efferent vestibular system of
      man.

PMID- 9641323
TI  - Ultrastructural localization of GABA-like immunoreactivity in the human utricular
      macula.
AB  - In the vertebrate vestibular periphery, gamma-aminobutyric acid (GABA) has long
      been presumed to be a neurotransmitter candidate. However, experimental reports
      about the localization and function of GABA in the vestibular systems of
      vertebrates are contradictory. In addition, there is no information in the
      literature concerning the localization of GABA in the human vestibular periphery.
      The present study investigates the ultrastructural localization of GABA-like
      immunoreactivity in the human utricular macula. A modified pre-embedding
      immunostaining electron microscopy technique was applied using two different
      commercially available polyclonal antibodies to GABA. GABA-like immunoreactivity
      is confined to the vesiculated nerve fibers and terminals of the human vestibular
      neurosensory epithelia. The GABA-containing nerve terminals make asymmetrical axo
      dendritic synapses with the afferent chalices surrounding the type I sensory hair
      cells. Type I and type II hair cells as well as afferent chalices are devoid of
      GABA-like immunoreactive staining. The present study demonstrates that GABA
      exists in the human vestibular periphery, and that GABA is a neurotransmitter
      candidate of the human efferent vestibular system.

PMID- 9641324
TI  - Alpha1A-adrenergic receptors mediate vasoconstriction of the isolated spiral
      modiolar artery in vitro.
AB  - Several lines of evidence suggest that cochlear blood flow is under the control
      of the sympathetic nervous system and that this control is mediated via alpha
      adrenergic receptors. The goal of the present study was to determine whether
      alpha-adrenergic receptors mediate vasoconstriction of the spiral modiolar artery
      and, if so, to determine which subtype dominates this response. Vascular diameter
      was measured with video microscopy in the isolated superfused spiral modiolar
      artery in vitro. The diameter of the spiral modiolar artery under control
      conditions was 61 +/- 2 microm (n = 60). Spontaneous vasomotion was observed in
      most specimens. Addition of norepinephrine to the superfusate caused a phasic
      vasoconstriction and an increase in the amplitude of vasomotion. These effects
      were limited to the vicinity of arteriolar branch points of the spiral modiolar
      artery. Norepinephrine-induced vasoconstriction occurred with EC50 of (1.9 +/-
      0.4) x 10(-5) M (n = 44) and the vascular diameter was maximally reduced by a
      factor of 0.87 +/- 0.01 (n = 29). Neither the phasic nature nor the EC50 of the
      norepinephrine-induced vasoconstrictions was altered in the presence of the beta2
      adrenergic receptor antagonist 10(-5) M ICI118551 or the nitric oxide synthase
      inhibitor 10(-4) M NOARG. In contrast, the alpha2-adrenergic receptor antagonist
      10(-7) M yohimbine and the alpha1-adrenergic receptor antagonist 10(-9) and 10(
      8) M prazosin caused a significant shift in the dose-response curve. The affinity
      constants (K(DB)) for yohimbine and prazosin were (5+/-2) x 10(-8) M (n=4) and
      (2.0+/-0.7) x 10(-10) M (n=18), respectively. The alpha1A-adrenergic receptor
      antagonist 10(-8) M 5-methyl urapidil and the alpha1D-adrenergic receptors
      antagonist 5 x 10(-6) M BMY7378 caused a significant shift in the dose-response
      curve. The K(DB) values for 5-methyl urapidil and for BMY7378 were (2.7 +/- 0.7)
      x 10(-10) M (n = 8) and (4.4 +/- 2.7) x 10(-7) M (n = 8), respectively. Further,
      total RNA was isolated from microdissected spiral modiolar arteries and the
      presence of transcripts for alpha1-adrenergic receptor subtypes was determined by
      reverse transcription polymerase chain reaction (RT-PCR). Primers specific for
      gerbil alpha1-adrenergic receptor subtypes were developed using RNA from rat and
      gerbil brain. Analysis of RNA extracted from the spiral modiolar artery revealed
      RT-PCR products of the appropriate size for the alpha1A-adrenergic receptor,
      however, no evidence for the alpha1B- and alpha1D-adrenergic receptor was found.
      Further, analysis of RNA extracted from blood, which was a contaminant of the
      microdissected spiral modiolar arteries, revealed no RT-PCR products. Sequence
      analysis of the RT-PCR product of the alpha1A-adrenergic receptor from the spiral
      modiolar artery confirmed its identity. Identity between the 175 nt gerbil
      sequence fragment and the known rat, mouse and human alpha1A-adrenergic receptor
      sequences was 90.9, 92.0 and 85.2%, respectively. These observations demonstrate
      that the spiral modiolar artery contains alpha1A-adrenergic receptors which
      mediate vasoconstriction at branch points.

PMID- 9641325
TI  - Detection of transcripts for delayed rectifier potassium channels in the Xenopus
      laevis inner ear.
AB  - Reverse transcriptase polymerase chain reaction (RT-PCR) was used to amplify
      sequences for delayed rectifier potassium (drk) channel transcripts in Xenopus
      laevis inner ear and brain. We used degenerate primers that spanned a region
      between the N-terminal cytoplasmic portion and a region located between the S2
      and S3 transmembrane domains of the potassium channel protein. When inner ear
      total RNA or brain mRNA was used as a template for RT-PCR, a unique product of
      the expected size (approximately 560 bp) was observed as a single band after
      electrophoresis on agarose gels. The PCR product from reactions using X. laevis
      genomic DNA as template was similarly sized, indicating a lack of introns in this
      region. The RT-PCR products from inner ear and brain were isolated, cloned, and
      sequenced. Sequence analysis showed that the X. laevis inner ear and brain clones
      were identical. Sequence alignments of the cloned RT-PCR products with posted
      GenBank sequences established that the drk sequences from X. laevis inner ear and
      brain share highest identity with larval X. laevis brain, mouse, rat, and human
      Kv2 sequences. Positive signals were obtained from inner ear and brain mRNA in
      Northern dot blots hybridized with digoxigenin labeled probes from the inner ear
      clone. Taken together, results provide evidence for the expression of Kv2
      sequences in the X. laevis inner ear and brain.

PMID- 9641326
TI  - Threshold-duration functions of chinchilla auditory nerve fibers.
AB  - The purpose of the present study was to measure the change in threshold as a
      function of stimulus duration in single auditory nerve fibers. Thresholds were
      measured at each neuron's characteristic frequency (CF) for eight stimulus
      durations ranging from 8 to 1024 ms. Using an adaptive, two-interval, forced
      choice threshold-tracking procedure with a 2-down, 1-up rule, thresholds were
      estimated based on a decision criterion of one spike or greater difference
      between tone and no-tone intervals. The results showed that mean thresholds
      decreased with increasing stimulus duration by approximately 14.6 dB over the
      range of durations tested. Analysis of group and individual data showed that
      thresholds decreased by approximately 6-7 dB per decade of duration. The slope of
      threshold improvement decreased systematically with increasing CF, consistent
      with previous physiological and psychophysical data.

PMID- 9641328
TI  - Basic response characteristics of auditory nerve fibers in the grassfrog (Rana
      temporaria).
AB  - Responses to free-field sound of 401 fibers from the VIIIth nerve of the
      grassfrog, Rana temporaria, are described. The spontaneous activities of the
      fibers ranged from 0 to 75 spikes/s, showing only weak correlation with frequency
      or sensitivity of the fibers. The highest spontaneous activities were
      approximately twice as high as reported previously for frogs. Best frequencies
      ranged from 100 to 1600 Hz and thresholds ranged from 21 to 80 dB SPL. The median
      dynamic range was 20 dB and the slopes of the rate-level curves ranged from 5 to
      20 spikes/(s-dB). Most of the units showed post-excitatory suppression (PS) of
      their spontaneous activity. The duration of PS increased with sound level, also
      in fibers showing a decrease in firing rate at high intensities. Most fibers
      showing one-tone suppression did not show PS at their best suppression
      frequencies. Strong suppression was observed also in very phasic cells giving one
      spike per stimulation. Therefore, the mechanism underlying PS is probably
      different from that underlying adaptation. The sharpening of the neural encoding
      of temporal parameters and the strong encoding of sound offset as well as onset
      caused by PS very likely is biologically important.

PMID- 9641327
TI  - Electrically evoked compound action potentials of guinea pig and cat: responses
      to monopolar, monophasic stimulation.
AB  - We recorded electrically evoked compound action potentials (EAPs) from guinea
      pigs and cats using monophasic current pulses delivered by a monopolar
      intracochlear electrode. By using simple stimuli, we sought results that could
      shed light on basic excitation properties of the auditory nerve. In these acute
      experiments, the recording electrode was placed directly on the auditory nerve.
      Responses to anodic and cathodic stimulus pulses were recorded separately to
      evaluate stimulus polarity effects. Several polarity-dependent properties were
      observed. Both EAP morphology and latency were polarity-dependent, with greater
      latencies for cathodic stimulation. Threshold stimulus level was also polarity
      dependent, but in different directions in the two species: cats had lower
      cathodic thresholds while guinea pigs had lower anodic thresholds. We also
      observed that the slopes of the EAP amplitude-level functions depended upon
      stimulus polarity. In most cases where EAP saturation amplitude could be
      measured, that amplitude was similar for anodic and cathodic stimuli, suggesting
      that either stimulus polarity can recruit all fibers, or at least a comparable
      numbers of fibers. The common findings (e.g., EAP morphology and polarity
      dependent latency) observed in these two species suggest results that can be
      extrapolated to responses obtained in humans, while the species-specific findings
      (e.g., dependence of threshold on polarity) may point to underlying anatomical
      differences that caution against overgeneralization across species. Some of our
      observations also bear upon hypotheses of how electrical stimuli may excite
      different sites on auditory nerve fibers.

PMID- 9641329
TI  - Partial left ventriculectomy and mitral valve repair for end-stage congestive
      heart failure.
AB  - OBJECTIVE: Partial left ventriculectomy (PLV), pioneered by Batista, has been
      proposed as an alternative treatment strategy in patients with refractory
      congestive heart failure. In order to analyze the midterm outcome of PLV and
      mitral valve (MV) repair and stratify patients according to risk, we
      prospectively studied 57 consecutive patients who underwent this procedure at the
      Cleveland Clinic Foundation (CCF). METHODS: Patients had a mean age of 53 years
      and were predominantly males (74%). In 95% the etiology of heart failure was
      idiopathic dilated cardiomyopathy. All patients had a left ventricular end
      diastolic diameter of >7cm and were in New York Heart Association (NYHA)
      functional classes III and IV. A total of 54 patients (95%) were awaiting heart
      transplantation. Preoperatively, requirements included inotropes in 23 (40%),
      intraaortic balloon pump counterpulsation in 3 (5.3%), and left ventricular
      assist device placement (LVAD) in 1 (1.8%). Concomitant procedures included MV
      repair (55 patients), MV replacement (2), tricuspid valve repair (34 patients),
      coronary artery bypass graft (CABG) (5), and aortic valve repair or replacement
      (1 patient each). RESULTS: Measurements preoperatively and at 3 months
      demonstrated improvement in left ventricular ejection fraction (14.4 +/- 7.7-23.2
      +/- 10.7%, P < 0.001), left ventricular end diastolic volume (254 +/- 85-179 +/-
      73 ml, P < 0.001) and left ventricular end diastolic diameter (8.4 +/- 1.1-6.3 +/
      0.9 cm, P < 0.001). Peak oxygen consumption (MVO2) increased from 10.6 +/- 3.9
      to 15.3 +/- 4.5 ml/kg per min (P < 0.001). Cardiac index did not change (2.2
      l/min per m2), although 40% had been on inotropes preoperatively and none were on
      inotropes at 3 months. NYHA functional class improved from 3.6 +/- 0.5
      preoperatively to 2.2 +/- 0.9 at 3 months (P < 0.001). LVAD support was required
      as rescue therapy in 11 patients (17%). Actuarial freedom from procedure failure,
      defined as death or relisting for transplant, was 58% at 1 year. Hospital
      mortality was 3.5% (n = 2). On follow-up, there were 7 late deaths (including 3
      sudden deaths) giving an actuarial survival of 82% at 1 year. Multivariate risk
      factor analysis revealed that age less than 40 years was associated with failure
      (P = 0.02). CONCLUSIONS: Although PLV with MV repair is now a surgical option in
      the treatment of end-stage congestive heart failure, caution is advised as early
      failures are unpredictable and mechanical support may be required as rescue
      therapy. Better risk stratification and patient selection may improve outcome.
      Further study is required to determine the procedure's exact role in the
      treatment of congestive heart failure.

PMID- 9641330
TI  - High-risk mitral valve replacement in severe pulmonary hypertension--30 years
      experience.
AB  - OBJECTIVE: In the past 30 years, 2316 patients underwent mitral valve replacement
      (MVR) at our institution; 382 of them had severe pulmonary hypertension
      (pulmonary artery pressure (PAP) > 50 mmHg; pulmonary vascular resistance (PVR),
      690 +/- 46 dyn/s per m2). We reviewed our early and late results in this high
      risk subgroup. METHODS: We used 336 mechanical and 46 biological devices for MVR.
      The follow-up was 95%, with an observation period of 3208 patient-years and a
      mean of 8.4 +/- 0.2 years per patient. The overall early mortality rate was 10.5%
      (n = 40) and stayed at about the same level over the years, although patients
      characteristics have changed to much older patients and more reoperations. To
      clarify this fact we divided our data in results according to the decades in
      which the operations were carried out. The clinical preoperative status and
      results were as follows (*P < 0.05; **P < 0.01 compared with previous decade). In
      the decades between 1963 and 1973 (I), 1974 and 1983 (11) and 1984 and 1993 (III)
      we operated on n = 95 (I), n = 185 (II), and n = 102 (III) patients with a mean
      age of 43 +/- 1 (I), 50 +/- 1** (II), and 58 +/- 1** (III) years. The incidence
      of reoperations among these patients was 3.2 (I), 4.9 (II), and 22.6%** (III).
      The early mortalities were 13.7 (I), 8.6* (II) and 10.8% (III); late mortalities
      lowered from 5.77 (I), over 4.95 (II), and up to 3.39%** (III) patients/year. The
      mean functional status according to New York Heart Association (NYHA) class
      improved from preoperatively 3.0 +/- 0.1 (I), 3.2 +/- 0.1 (II) and 3.3 +/- 0.1
      (III) to 2.4 +/- 0.2 (I), 2.4 +/- 0.1 (II) and 2.3 +/- 0.1 (III) postoperatively.
      RESULTS: Compared with routine elective MVR with a mortality rate of 3.6% (P <
      0.01), early mortality is high. But once the patient survives the perioperative
      course, late results show no difference compared with patients without pulmonary
      hypertension. The functional results as well are not significantly different. In
      spite of on average 15 years older multimorbid patients with therefore higher
      complication rates, early results improved slightly, which could be explained by
      better operative techniques, perioperative treatment and nursing (online
      monitoring with immediate therapeutic substitution). Surprisingly the increased
      number of reoperations had no negative impact on patients' outcomes. CONCLUSION:
      According to our results, we recommend MVR in severe pulmonary hypertension even
      in the elderly, with a high but acceptable risk and good long-term results.

PMID- 9641331
TI  - A comparative study of structures comprising the thoracic outlet in 250 human
      cadavers and 72 surgical cases of thoracic outlet syndrome.
AB  - OBJECTIVE: We have hypothesized that variations in fibrous, muscular and osseous
      structures with the potential to entrap the brachial plexus occur within the
      thoracic outlet of the normal population; and that these variations are different
      in pattern and frequency from those in patients presenting with thoracic outlet
      syndrome (TOS). METHODS: Structural anomalies with potential for entrapping
      elements of the brachial plexus were examined following dissections of the
      posterior triangle of the neck in 250 human cadavers (N = 500 thoracic outlet
      dissections) and catalogued jointly by an anatomist and a thoracic surgeon. The
      pattern and frequency of anomalies in the 250 cadavers was compared to that
      encountered in 72 surgical cases of removal of the first rib for relief of
      symptomatic TOS (N = 72 procedures, 55 patients). RESULTS: Relevant structural
      variations were encountered in 46% of cadavers, exhibiting no left right or
      gender preference overall. When compared with the surgical group in which 100%
      exhibited structurally relevant anomalies, significant differences in pattern of
      anomalous structures and gender distribution were revealed. Anomalies posterior
      to the brachial plexus, ranging from fibrous bands to cervical ribs in both
      groups, were prevalent in the surgical group. A 'scissors-like' pattern, with
      neural entrapment by anterior and posterior anomalies was frequently encountered
      in females. CONCLUSIONS: Based on these data and embryological considerations, we
      propose a revised and simplified classification of impingement mechanisms within
      the anatomic thoracic outlet. Comparing these data to radiological imaging and
      observations at surgery, we offer a new perspective for the investigation and
      management of patients with TOS.

PMID- 9641332
TI  - Technique to reduce air leaks after pulmonary lobectomy.
AB  - OBJECTIVE: Patients undergoing pulmonary resections often present postoperative
      air leaks of varying magnitude and duration; this complication is more frequent
      with incomplete or absent interlobar fissures. Small leaks close spontaneously
      within 5-7 days; larger leaks may persist longer and could be associated with
      increased morbidity and prolonged hospitalization. We evaluated the role of
      different techniques to complete interlobar fissures before pulmonary lobectomy
      to prevent postoperative air leaks and reduce hospital stay and costs. METHODS: A
      total of 30 patients undergoing pulmonary lobectomy for lung cancer and
      presenting incomplete interlobar fissures that needed to be opened both
      anteriorly and posteriorly were randomized into three groups. In Group I,
      fissures were created with a GIA stapler and buttressed with bovine pericardial
      sleeves. In Group II, we used TA 55 staplers alone; in Group III we used the 'old
      fashion' cautery, clamps and silk ties. The three groups were homogeneous for
      age, type of pulmonary resection and stage of the tumor. The duration of
      postoperative air leaks and hospital stay were compared with the one-way variance
      analysis. RESULTS: Postoperative air leaks for Groups I, II and III persisted for
      2 +/- 0.94, 5.3 +/- 2 and 5.3 +/- 1.7 days, respectively. Mean hospital stay was
      4.4 +/- 0.96, 7.8 +/- 2.14 and 7.2 +/- 1.5, respectively. The difference between
      groups in terms of duration of postoperative air leaks and hospital stay was
      statistically significant (P = 0.0001). CONCLUSIONS: The use of GIA staplers and
      pericardial sleeves to complete interlobar fissures for pulmonary lobectomy
      significantly reduces the duration of postoperative air leaks and hospital stay;
      no complications were associated with this technique.

PMID- 9641333
TI  - Coronary bypass surgery: what is changing? Analysis of 3834 patients undergoing
      primary isolated myocardial revascularization.
AB  - OBJECTIVE: The patient population undergoing myocardial revascularization has
      changed during the last few years. Knowledge of these changes, and of the
      subsequent influence on morbidity and/or mortality is important, not only for up
      dating quality control, but also to support decision-making in financial and
      economical aspects, and in further research concerning coronary artery surgery.
      METHODS: Pre-, per- and postoperative data of 3834 primary isolated coronary
      bypass operations, January 1987 December 1995 were analyzed. The total group was
      divided into three time cohorts. Group A: 1987 1989 (n = 1292); group B: 1990
      1992 (n = 1130); and group C: 1993-1995 (n = 1412). RESULTS: Mean age increased
      from 60.4 +/- 9.0 (S.D.) years in group A to 62.9 +/- 9.9 (S.D.) years in group C
      (P < 0.0005). Patients with insulin-dependent diabetic (P = 0.005), uro
      nefrological (P = 0.002), pulmonary (P < 0.0005)and neurological (P = 0.003)
      pathology increased significantly, and there was a significant increase in the
      use of arterial grafts (P < 0.05). Postoperative, hospital mortality remained
      stable (+/- 2.5%). However, there was a significant increasing percentage of
      patients with pulmonary (P = 0.04), neurological (P = 0.02) and uro-nefrological
      (P < 0.0005) problems. CONCLUSION: During the last few years there has been a
      trend in myocardial revascularization of older patients, with more coexisting
      disease. Despite the fact that hospital mortality seems stable, there is an
      increase in major postoperative morbidity.

PMID- 9641334
TI  - Cerebral oxygenation during paediatric cardiac surgery: identification of
      vulnerable periods using near infrared spectroscopy.
AB  - OBJECTIVE: Neurologic sequelae remain a well recognised complication of
      paediatric cardiac surgery. Monitoring of cerebral oxygenation may be a useful
      technique for identifying vulnerable periods for the development of neurologic
      injury. We sought to measure regional cerebral oxygenation in children undergoing
      cardiac surgery using near infrared spectroscopy to ascertain such vulnerable
      periods. METHODS: Observational study of 18 children (median age 1.3 years)
      undergoing cardiac surgery (17 with cardiopulmonary bypass, 8 with circulatory
      arrest). Regional cerebral oxygenation was monitored using the INVOS 3100
      cerebral oximeter and related to haemodynamic parameters at each stage of the
      procedure. RESULTS: Prior to the onset of bypass, 10 patients had a decrease in
      regional cerebral oxygenation of > or = 15% points, reaching an absolute
      haemoglobin saturation less than 35% in 5 cases. The most common cause was
      handling and dissection around the heart prior to and during caval cannulation.
      With institution of bypass, regional cerebral oxygenation increased by a mean 18%
      points to a mean maximum of 75%. During circulatory arrest regional cerebral
      oxygenation decreased with rate of decay influenced by temperature at onset of
      arrest (0.25%/min at < 20 degrees C; 2%/min at > 20 degrees C). Reperfusion
      caused an immediate increase in regional cerebral oxygenation followed by a
      decrease during rewarming. Discontinuation of bypass caused a precipitous
      decrease in regional cerebral oxygenation in 5 patients, reaching less than 50%
      in 3 patients. CONCLUSIONS: These observations suggest that the pre- and early
      post-bypass periods are vulnerable times for provision of adequate cerebral
      oxygenation. Near infrared spectroscopy is a promising tool for monitoring O2
      supply/demand relationships especially during circulatory arrest.

PMID- 9641335
TI  - Cardiac troponin I as an early marker of myocardial damage after coronary bypass
      surgery.
AB  - STUDY OBJECTIVE: To evaluate the performance of cardiac specific markers, cardiac
      troponin I (cTnI) and CK-MB by mass assay (CK-MB mass), for the early diagnosis
      of myocardial ischemia and/or infarction after coronary bypass surgery. METHODS:
      Prospective clinical, electrocardiograpic and biologic follow-up of 117 patients
      undergoing isolated coronary surgery with the use of intermittent anterograde
      normothermic blood cardioplegia. Blood samples for biochemical analysis were
      drawn before surgery (T0) and at 2 (T1), 6 (T2), 10 (T3) and 20 h (T4) after
      aortic cross-clamp release. Without knowledge of the biochemical data, patients
      were classified according to the electrocardiographic evolution into two groups:
      group 1, uneventful recovery and group 2, evidence of ischemia/infarction based
      on continuous ST-T segment monitoring and 12-lead ECG. RESULTS: No patients had
      abnormal markers at T0. At T1, although both markers were elevated, no difference
      was noted between the two groups. At T2, 6 h after surgery, cTnI and CK-MB mass
      levels were significantly higher in group 2 than in group 1 (median = 17
      microg/l, Interquartile Range (IR): 14.7-27.3 vs. 3.1 microg/l, IR 1.9-5.3 for
      cTnI and median 42.5 microg/l, IR: 27.1-95.7 vs. 13.6 microg/l, IR: 9.5-18.5 for
      CK-MB mass). A receiver operating characteristic (ROC) curve analysis shows that
      a cTnI value of 13.1 microg/ml has 100% specificity and 90% sensitivity to
      separate both groups, whereas a value of 33.2 microg/ml for CK-MB mass has a
      specificity of 100% and a sensitivity of 73%. At T3 and T4, the same difference
      was noted between the groups. cTnI values in all six patients with a Q-wave
      infarction were > or = 20 ng/ml, whereas only one of five patients with prolonged
      ischemia had cTnI level > 20 ng/ml. CONCLUSION: As soon as 6 h postoperatively,
      cTnI and CK-MB by mass assay were able to separate those patients with an
      uneventful recovery from those with significant ischemia. This is particularly
      useful in frequent cases when the ECG is difficult to interpret.

PMID- 9641336
TI  - von Willebrand factor and urinary albumin excretion are possible indicators of
      endothelial dysfunction in cardiopulmonary bypass.
AB  - OBJECTIVE: Experimental evidence suggests that cardiopulmonary bypass (CPB)
      associated inflammatory response leads to endothelial injury and increased
      permeability, but this has been difficult to show clinically. We have
      investigated the use of von Willebrand factor (vWF), and urinary albumin
      excretion, as measured by the urinary albumin creatinine ratio (ACR), to
      demonstrate this. METHODS: A total of 23 patients undergoing elective coronary
      artery bypass grafting were studied. Complement fragment C3a, leukotrienne B4
      (LTB4), interleukin 6 (IL6), neutrophil elastase, vWF and ACR were measured on
      anaesthetic induction (baseline), 20 min after starting CPB, 5 min after cross
      clamp removal, 5 min, 2, 6 and 24 h after termination of CPB. Anaesthetic, CPB
      and myocardial protection techniques were standardised. ANOVA was performed by
      using the distribution free Friedman test for each measured parameter. When
      significance differences were found (P < 0.05), post hoc analysis with Wilcoxon
      signed rank test was used for comparison of each time point with the base line
      level and differences were only accepted as significant following the Bonferroni
      correction (P < 0.008). Summary measures of peak versus peak and area under the
      cure were also analysed for ACR with vWF. RESULTS: Peak vs. baseline levels for
      C3a were 4.9 vs. 2.1 microg/ml (P < 0.0001), LTB4 was 800 vs. 20 pg/ml (P <
      0.0001), neutrophil elastase was 250 vs. 115 ng/ml (P < 0.001), IL6 was 620 vs.
      1.4 pg/ml (P < 0.0001), vWF was 2.2 vs. 1.3 IU/ml (P < 0.0001) and ACR was 17.6
      vs. 2.0 mg/mmol (P < 0.0001). C3a, LTB4 and ACR peaked during the operation.
      Neutrophil elastase peaked at 2 h following CPB. IL6 and vWF peaked at 6 h
      following CPB. The correlation coefficient between vWF and ACR following peak
      versus peak analysis was 0.48 (P = 0.035), and area under the curve analysis was
      0.6 (P < 0.01). CONCLUSION: These results demonstrate that endothelial
      permeability and injury, as measured by urinary albumin excretion and vWF,
      respectively, are related and the use of these easily detectable and sensitive
      biochemical markers warrants further investigation.

PMID- 9641337
TI  - Transmyocardial laser revascularization using the Holium-YAG laser for treatment
      of end stage coronary artery disease.
AB  - OBJECTIVE: Transmyocardial Laserrevascularization (TMLR) is a treatment for end
      stage coronary artery disease, that is not eligible for surgery or PTCA. The
      experience with TMLR using the Holium YAG laser is presented. METHODS:
      Transmyocardial Laserrevascularization (TMLR) was performed in 28 patients with
      end stage coronary artery disease, using a new Holium YAG Laser. All patients
      were refractory to a maximum of medical treatment. In 16 patients TMLR was used
      as the sole therapy with a mean of 28 +/- 4 laser created channels (group A). In
      12 patients TMLR was combined with coronary artery bypass graft surgery with a
      mean of 17 +/- 2 channels and 1.3 +/- 0.2 grafts (group B). Preoperative and
      postoperative examination included angina classification, exercise test and
      thallium scan. RESULTS: Postoperative demographics were as follows: (a) age 55-71
      years (mean 63.9 +/- 6.5 years); (b) Canadian Cardiovascular Society Angina Scale
      (CCS) mean 3.3 +/- 0.5; (c) ejection fraction 35-71% (mean 54 +/- 13.7%). All
      patients had an peri- and postoperative course without major complications and a
      duration of hospitalization of 8.2 +/- 1.9 days. Minor complications were a
      clinically silent myocardial infarction n = 1, atrial arrhythmia n = 2 and
      pneumothorax n = 2. A follow-up at 3-12 months was completed in 23 patients
      (82%). Only one patient died 5 months after surgery (cardiac related death). In
      all remaining patients CCS had improved with a mean of 1.6 +/- 0.3, P < 0.01. The
      exercise tolerance test (bicycle) improved in 17 patients with a mean 26.5 +/-
      6.5 watt, P < 0.01. The ejection fraction did not significantly improve. The
      repeated thallium scan did not show an improvement of perfusion in the lasered
      area to a significant level. Subjective benefit from the treatment was confirmed
      by 21 patients. CONCLUSION: Based on these results it is concluded that TMLR with
      the Holium-YAG laser is a safe therapy for the treatment of end stage coronary
      artery disease. The postoperative clinical results are comparable to that
      achieved with the CO2-laser in terms of reducing angina symptoms and improving
      exercise tolerance and quality of life. However. relief of symptoms is not
      correlated to objective findings of cardiac function.

PMID- 9641338
TI  - Electron-microscopic findings after transmyocardial laser revascularization in an
      acute ischemic pig model.
AB  - OBJECTIVE: The clinical benefit in terms of angina reduction after
      transmyocardial laser revascularization (TMLR) in patients with diffuse coronary
      artery disease who are not candidates for conventional procedures has been
      proved. The exact mechanisms of TMLR however, are still unknown. The aim of this
      study was to investigate the cellular changes in relation to intramyocardial
      partial oxygen pressure (ptiO2) after TMLR in a model of acute ischemia in pigs
      by electron microscopical methods (TEM). METHODS: Seven pigs were included in
      this study (five animals with acute myocardial ischemia and additional TMLR and
      two animals with acute myocardial ischemia and without TMLR for control). Acute
      ischemia was induced by ligation of diagonal branches of the left anterior
      descending artery (LAD). Intramyocardial partial oxygen pressure was measured
      before induction of ischemia and thereafter continuously for up to 6 h in all
      animals. Biopsies of all animals were taken before induction of ischemia and
      thereafter at 30 min, 3 and 6 h. Analysis of the myocardial ultrastructure was
      focused on mitochondria, cell nucleus, T-tubules and myofibrils. RESULTS:
      Ultrastructural changes were seen in all animals. At 6 h after induction of
      ischemia, mitochondria showed a destruction of the internal as well as the
      external membrane and of the cristae. The nuclei showed margination of the
      chromatin. Myofibrils were characterized by ruptures in the Z-stripes. Lipid
      droplets as an indicator of ischemia could be identified. PtiO2 between 40 and 80
      mmHg before intervention decreased down to 0-2 mmHg within the first 9 min after
      diagonal branch ligation and did not increase even after TMLR. CONCLUSIONS: In
      this acute ischemic model using pigs, TEM evaluation following TMLR proves
      irreversible changes of the myocardial ultrastructure. Furthermore, TMLR was not
      able to increase ischemically induced decrease of ptiO2. These data provide some
      evidence that TMLR thus, may not be able to ameliorate acute ischemia at least in
      the pig model. Further investigations are needed to investigate the effect of
      TMLR in chronic myocardial ischemia.

PMID- 9641339
TI  - Non-invasive evaluation of mammary artery flow reserve and adequacy to increased
      myocardial oxygen demand.
AB  - OBJECTIVE: To evaluate the flow reserve and adequacy to meet myocardial requests
      in stress conditions of mammary artery-left anterior descending (IMA-LAD) grafts
      using a non-invasive method. METHODS: Patients (20) with angiographic evidence of
      normofunctioning left IMA-LAD grafts were submitted to dypiridamole Tl201
      myocardial scintigraphy and concomitant transthoracic echo-doppler evaluation of
      the IMA flow at a mean interval of 32.5 months after surgery. RESULTS: Under
      basal conditions, the mean peak and end flow velocities in systole were 0.39 and
      0.06 m/s, respectively. In diastole, the mean peak and end flow velocities were
      0.27 and 0.02 m/s and mean tele-diastolic flow velocity was 0.14 m/s, with a mean
      systolic/diastolic ratio of 1.51. After dypiridamole infusion, mean systolic
      velocities were 0.47 (peak) and 0.23 (end) m/s, respectively + 20 and + 283%,
      whereas mean diastolic velocities were 0.56 (peak) and 0.06 (end) m/s, +107 and
      +200%, respectively. Mean tele-diastolic flow velocity increased to 0.32 m/s
      (+128%) and the systolic-diastolic index changed to 0.85. In all cases no
      significant scintigraphic evidence of induced ischemia was demonstrated in the
      LAD region. CONCLUSIONS: Transthoracic echo-doppler evaluation combined with
      Tl201 myocardial scintigraphy is a useful tool for the assessment of IMA flow
      reserve and adequacy to stress conditions. In the late postoperative period, the
      IMA shows the possibility of increasing the flow velocity, almost 2-fold; the
      increase in flow is prevalently diastolic and leads to a complete reversal of the
      physiological systolic/diastolic flow ratio. The flow reserve of IMA is always
      able to meet the augmented myocardial oxygen demand after dypiridamole infusion.

PMID- 9641340
TI  - Endothelium-dependent and endothelium-independent flow reserve in vascular
      regions supplied by the internal mammary artery before and after bypass grafting.
AB  - OBJECTIVE: It was the goal of this study to compare endothelium-dependent and
      endothelium-independent flow reserve in vascular regions supplied by the left
      internal mammary artery before and after bypass graft surgery. METHODS: The
      native internal mammary artery in situ was investigated in 13 patients (age 61.8
      +/- 8.0 years) with angiographically proven coronary artery disease. The internal
      mammary artery after bypass grafting was investigated in ten patients (age 60.8
      +/- 7.3 years) 3.5 +/- 2.8 years after the operation. Flow reserve was evaluated
      endothelium-dependent with acetylcholine (ACh 25 and 50 microg i.c.) and
      endothelium-independent with nitroglycerin (NTG 0.3 mg i.c.) followed by
      papaverin (10 mg i.c.). Flow indices were calculated from intraluminal Doppler
      blood flow velocity measurements and the vascular cross-sectional area as
      determined by quantitative angiography. An index for vascular resistance was
      defined as the ratio of pressure gradient and resting or peak flow. RESULTS:
      After endothelium-dependent stimulation with acetylcholine 25 microg (50 microg),
      flow in the internal mammary increased by 352.3 +/- 152% (412 +/- 145%) before
      surgery, whereas it increased only by 213 +/- 134% (193 +/- 120%) after surgery
      (P < 0.05). Endothelium independent stimulation with papaverin resulted in a flow
      increase of 391 +/- 234% before surgery vs. 315 +/- 135% after surgery (n.s.).
      The resistance index decreased after endothelium-dependent stimulation with
      acetylcholine 25 microg(50 microg) to 35 +/- 16.8% (28 +/- 8.9%) before surgery,
      whereas it decreased only to 59 +/- 26% (72 +/- 43%) after surgery (P < 0.05).
      Endothelium independent stimulation with papaverin resulted in a decrease of the
      vascular resistance index to 31 +/- 14% before surgery vs. 32 +/- 14% after
      surgery (n.s.). CONCLUSION: Vascular regions supplied by the internal mammary
      artery as a graft demonstrate a significantly reduced endothelium-dependent flow
      reserve but a preserved endothelium-independent flow reserve as compared to
      vascular regions supplied by the native internal mammary artery. The selective
      decrease in endothelium-dependent flow reserve may be due to microvascular
      changes in the myocardial region supplied by the internal mammary artery after
      bypass grafting.

PMID- 9641341
TI  - Long-term prognosis of surgically-treated aortic aneurysms and dissections in
      patients with and without Marfan syndrome.
AB  - OBJECTIVE: Aortic aneurysms and dissections are the leading causes of premature
      death in Marfan syndrome (MfS). This study aims to compare long-term results of
      surgically treated aortic aneurysms and dissections in patients with and without
      MfS in respect to early and late prognosis. METHODS: From March 1975 to August
      1994, 33 patients with classic MfS (group A, age 34.2 +/- 9 years) and 298
      patients with non-fibrillinopathic aortic disease (group B, age 54 +/- 13 years)
      underwent aortic surgery. Acute dissections occurred in 57.6 (A) versus 37.9%
      (B). A total of 54.6% of patients in group A were treated with a composite graft
      versus 16.4% in B. The aortic arch and the descending aorta was replaced in 30.4%
      of MfS patients and 24.9% of patients without MfS. RESULTS: We observed 7 (25.0%,
      A) versus 35 (14.2%, B) late deaths among the 28 (A) versus 247 (B) early
      survivors. In 5 patients (17.9%) of A and 8 patients (3.2%) of B, late death was
      caused by redissection or recurrent aneurysm (P < 0.001). Long-term survival
      after 5, 10 and 15 years in group A was 82 +/- 7, 60 +/- 11 and 30 +/- 22%, and
      75 +/- 3, 69 +/- 3 and 64 +/- 4% in group B. A total of 22 reoperations were
      performed in 11 MfS patients, 17 reoperations were due to recurrent aortic
      diseases. Three of the 8 patients underwent reoperation after Wheat procedure
      because of sinus valsalva aneurysm. None of the patients with composite graft
      replacement needed reoperation in this segment, but 3 patients suffered from
      redissection at the proximal aortic arch. In group B, reoperations were
      significantly less frequent (10.7%) compared to MfS patients (66.7%; P < 0.001).
      CONCLUSIONS: Surgical treatment of aortic disease in MfS patients is associated
      with a high risk of redissection and recurrent aneurysm. If the ascending aorta
      needs to be replaced, we recommend the composite graft technique and a more
      aggressive approach to reduce the frequency of distal reoperations. In order to
      reduce the high reoperation rate in MfS patients, frequent clinical follow-up may
      contribute to improve life expectancy in MfS patients.

PMID- 9641342
TI  - Transforming growth factor-beta1 and lung allograft fibrosis.
AB  - OBJECTIVES: Transforming growth factor beta1 (TGF-beta1) is a potent
      immunosuppressive cytokine that promotes fibrosis by enhancing the synthesis of
      extracellular matrix components. The repair process following lung allograft
      injury is due to rejection or infection replaces lung parenchyma by fibrotic
      tissue, leading to pulmonary dysfunction. The role of TGF-beta1 in this excessive
      healing process and increasing the risk of infection is unknown. METHODS: We
      analysed our patient data to investigate the relevance of different factors on
      allograft fibrosis and its correlation with TGF-beta1. Fibrosis was graded in H
      and E stained sections. TGF-beta1 genotype was determined in all patients.
      RESULTS: Patients were aged between 16 and 62 years (mean age of 39.6 years).
      Procedures were heart/lung (n = 32), double lung (n = 18), and SLT (n = 41). A
      total of 46 patients had lung allograft fibrosis diagnosed in transbronchial
      biopsies sections. Patients who had developed interstitial fibrosis had
      significantly more acute rejection episodes (mean 3.4 +/- 2.8) compared with
      patients without fibrosis (mean 2.1 +/- 2.2) (P = 0.024). The presence of
      eosinophils in the interstitium preceded and were associated with the development
      of fibrosis regardless of the rejection grade (P = 0.0001). TGF-beta1 was heavily
      expressed in sections with fibrosis with a mean score of 6.8 +/- 2.9 compared
      with 2.4 +/- 0.6 in sections with no fibrosis (P < 0.0001). TGF-beta1 expression
      correlated positively with fibrosis grades (P < 0.0001). The mean survival for
      patients with a fibrosis score > 6 is 892.4 +/- 73 days compared with mean
      survival 427 +/- 78 in patients with scores < 6 (P = 0.0001). Patients who
      developed fibrosis had homozygous TGF-beta1 genotype that correlates with
      excessive TGF-beta1 expression (P = 0.01). The use of cardiopulmonary bypass was
      associated with the development of excessive fibrosis (P = 0.02), and 7 patients
      who had severe fibrosis died of septicaemia (17.5%). FEV1 (forced expiratory
      volume) was significantly higher in patients without fibrosis (1870 +/- 111 ml
      versus 1590 +/- 160; P = 0.02). CONCLUSIONS: The risks of lung allograft fibrosis
      increases with recurrent rejection, tissue eosinophilia, homozygous TGF-beta1
      genotype and the use of bypass machine. Fibrosis was associated with higher
      mortality and morbidity might be explained by the TGF-beta1 immunosuppressive and
      fibrotic properties. Immunological strategies to down-regulate TGF-beta1
      production might improve survival and function of lung allografts.

PMID- 9641343
TI  - Alveolar expansion itself but not continuous oxygen supply enhances postmortem
      preservation of pulmonary grafts.
AB  - OBJECTIVE: If lungs could be retrieved for transplant after circulatory arrest,
      the shortage of donors might be significantly alleviated. Great controversy still
      exists concerning the optimal mode of preservation of pulmonary grafts in these
      non-heart-beating donors. METHODS: Graft function was measured in an isolated
      room air-ventilated rabbit lung model during reperfusion with homologous, diluted
      (Hb +/- 8.0 g/dl) and deoxygenated (PaO2 +/- 40 mmHg) blood up to 4 h. Five
      groups of cadavers (n = 4 in each group) were studied: In the control group,
      lungs were immediately reperfused. In the other groups, cadavers were left at
      room temperature for 4 h after death with lungs either deflated (group 1),
      inflated with room air (group 2), or ventilated with room air (group 3) or 100%
      nitrogen (group 4). RESULTS: After 1 h of reperfusion, significant differences
      were noted between group 1 and groups 2, 3, and 4 in peak airway pressure (27 +/-
      5 cm H2O vs. 15 +/- 1 cm H2O, 17 +/- 2 cm H2O, and 16 +/- 1 cm H2O, respectively;
      P < 0.05), in weight gain (137 +/- 24 vs. 31 +/- 7, 30 +/- 3, and 30 +/- 2%,
      respectively; P < 0.05), and in veno-arterial oxygen pressure gradient (9 +/- 5
      vs. 95 +/- 13, 96 +/- 7 and 96 +/- 4 mmHg, respectively; P < 0.05). Also, wet-to
      dry weight ratio at end of reperfusion was significantly different (10.2 +/- 1.0
      vs. 6.0 +/- 0.3. 5.2 +/- 0.3 and 5.4 +/- 0.5, respectively; P < 0.05). No
      significant differences in any of these parameters were observed between groups
      2, 3, and 4. CONCLUSIONS: These data suggest that: (1) pulmonary edema will
      develop in atelectatic lungs if reperfusion is delayed for 4 h after death; (2)
      postmortem room air-inflation is as good as ventilation in prolonging warm
      ischemic tolerance; (3) ventilation with room air is no different from that with
      nitrogen; (4) therefore, prevention of alveolar collapse appears to be the
      critical factor in protecting the warm ischemic lung from reperfusion injury
      independent of continuous oxygen supply.

PMID- 9641344
TI  - Effect of a short period of warm ischemia after cold preservation on reperfusion
      injury in lung allotransplantation.
AB  - OBJECTIVE: A short period of warm ischemia during lung allograft implantation is
      inevitable. We studied the effect of 2 h of warm ischemia before implantation
      after 18 h of cold preservation on reperfusion edema and pulmonary hemodynamics
      in a large animal model. METHODS: Left lung transplantation was performed in ten
      weight-matched pigs (25-31 kg). Donor lungs were flushed with 1.5 l cold (1
      degree C) LPD solution and preserved for 20 h. In Group I (n = 5) the grafts were
      preserved for 20 h at 1 degree C and topically cooled with ice slush during
      implantation until reperfusion. In Group II (n = 5) lungs were stored at 1 degree
      C for 18 h followed by 2 h preservation at room temperature (20 degrees C).
      Topical cooling was not used during implantation. At 1 h after reperfusion the
      recipient contralateral right pulmonary artery and bronchus were ligated to
      assess graft function only. Extravascular lung water index (EVLWI), intrathoracic
      blood volume (ITBV), mean pulmonary artery pressure (PAP) and cardiac output (CO)
      were assessed during a 4 h observation period. Quantitative myeloperoxidase (MPO)
      activity and thiobarbituric acid-reactive substance (TBARS) levels as an
      indicator for lipid peroxidation were determined in allograft tissue samples
      taken 5 h after reperfusion. RESULTS: In Group II a tendency to improved
      pulmonary vascular resistance and cardiac output was noted. Surprisingly, lung
      edema, assessed by EVLWI, did not increase in animals with warm ischemia. Even a
      tendency to a reduced EVLWI was noted. However, differences between groups did
      not reach statistical significance. Gas exchange did not differ statistically
      significant between groups. CONCLUSION: Our results indicate that a short period
      of warm ischemia before reperfusion does not lead to increased pulmonary edema.
      In animals with a short period of warm ischemia before reperfusion, even a
      tendency to reduced posttransplant lung reperfusion injury was noted. In this
      model, topical graft cooling during lung implantation did not improve
      posttransplant graft function.

PMID- 9641345
TI  - Right ventricular function after brain death: response to an increased afterload.
AB  - OBJECTIVE: A major cause of early postoperative morbidity and mortality after
      cardiac transplantation is right ventricular (RV) failure which is attributed to
      the inability of the donor's RV to acutely compensate for the recipient's
      elevated pulmonary vascular resistance. This study was performed to determine:
      (1) the acute effects of brain death on the RV function; and (2) the adaptation
      potential of the RV to a progressive increase in RV afterload. METHODS: In 13
      anesthetized, open-chest dogs (eight with brain death vs. five control with sham
      operation), brain death was induced by inflation of a subdural balloon catheter.
      Heart rate, RV systolic and end-diastolic pressure (RVSP, RVEDP), pulmonary
      arterial pressure (PAP), and cardiac output (CO), and pressure-length loops
      (sonomicrometry) were recorded. Afterload increase was induced 2 h after brain
      death induction by constriction of the pulmonary artery with an increase in RVP
      from 25 to 50 mmHg in 5 mmHg steps. RESULTS: Cushing phenomenon occurred within a
      few minutes after brain death induction, with a significant increase of HR (229
      +/- 10 vs. 89 +/- 6 min(-1), P < 0.001), CO (3.2 +/- 0.2 vs. 1.7 +/- 0.1 l/min, P
      < 0.001), PAP (30.4 +/- 2.5 vs. 15.5 +/- 1.3 mmHg, P < 0.01) RVSP (55 +/- 5 vs.
      23 +/- 2 mmHg, P < 0.001) and RVEDP (7.4 +/- 0.9 vs. 3.3 +/- 0.6 mmHg, P <
      0.001). All these values were also significantly (P < 0.01) higher than the time
      corresponding values of the control group. The analysis of the pressure-length
      loops showed a hypercontractile state. Within 15-60 min, all parameters turned to
      baseline and remained stable for up to 2 h. When afterload was increased
      progressively, RVEDP increased markedly in the brain death and slightly in the
      control group (9.4 +/- 0.7 vs. 4.2 +/- 1.1 mmHg, P < 0.01, at RVSP = 50 mmHg). On
      the other hand, the increase of peak positive dP/dt was significantly higher in
      the control group (430 +/- 37 vs. 644 +/- 55 mmHg/s, P < 0.01, at RVP = 50 mmHg).
      However, global RV pump function characterized by CO and stroke work was similar
      in both groups. While regional RV contractility remained unchanged in the brain
      death group in terms of pressure-length relationships, RV contractility
      significantly increased in the control group. CONCLUSION: (1) Brain death per se
      does not result in an acute impairment of RV function. (2) While control animals
      adapt to an increased afterload by the homeometric, as well as the heterometric
      regulation, after brain death, an increase in RV preload follows elevations in RV
      afterload by the Frank-Starling mechanism subserving the increased stroke work
      required to ensure unchanged pump function.

PMID- 9641346
TI  - Gene transfer into rat heart-derived endothelial cells.
AB  - OBJECTIVE: Progressive graft arteriosclerosis is responsible for the majority of
      late deaths in cardiac transplant recipients. Despite many investigations, the
      pathogenesis of this disease remains undetermined and its control inadequate. A
      somatic gene transfer during the cold ischemic time and thus before
      transplantation might be a new therapeutic tool. This approach allows a long
      incubation time of the DNA and a safe transfer with liposomes and transferrin
      with less adverse effects for the organ recipient. METHODS: The target cells
      (microvascular endothelial cells (MVECs)) for this gene transfer were isolated
      from rat hearts by perfusion with collagenase via an aortic cannulae. The cells
      were purified by changing the medium 30 min after subcultivation in order to
      remove fibroblasts and smooth muscle cells. The endothelial cells (ECs) were
      identified by typical morphology and the uptake of Dil-Ac-LDL. The gene transfer
      was carried out with a beta-galactosidase reporter plasmid (pCMVbeta), cationic
      liposomes (Lipofectin), and transferrin. Different transfection solutions were
      prepared with or without serum, and with different plasmid-liposome ratios and
      transferrin concentrations. The transfer rate was monitored with a
      semiquantitative orthonitrophenyl-beta/-D-galactoside (ONPG) assay and
      histologically by X-Gal staining. The cytotoxicity of this procedure was
      determined with a colorimetric ELISA with Alamar blue. The cardioplegic property
      of the transfection solution was tested in a Langendorff perfusion system
      monitoring the coronary blood flow over time after a cold ischemic time of 4 h.
      RESULTS: The maximal gene expression could be detected after transfection with 4
      microl Lipofectin, 2 microg pCMVbeta, and 16 microg transferrin/200 microl
      transfection solution. Under these conditions 60% of the cells showed a blue
      staining with X-Gal. Only 20% of the cells died during transfection. The lowest
      cytotoxicity during cold ischemic time for ECs was assessed with normal cell
      culture medium and the Buckberg solution. The best coronary flow rates after 4 h
      cold ischemia of the heart were measured for cardioplegia with St. Thomas and
      Buckberg solutions. In summary, the best transfection solution with a good
      cardioplegic property was the Buckberg solution. CONCLUSIONS: Finally, the
      results of this study show that an effective DNA delivery with a low toxicity
      into ECs is possible with a combination of liposomes and transferrin. This method
      might be useful for a safe and effective gene transfer into solid organs during
      the cold ischemic time and thus a therapeutic tool for chronic rejection.

PMID- 9641347
TI  - Influence of heat stress on myocardial metabolism and functional recovery after
      cardioplegic arrest: a 31P N.M.R study.
AB  - OBJECTIVE: Heat stress and induction of heat shock proteins confer protection
      against myocardial ischemia-reperfusion injury; however the precise mechanisms of
      this effect remain unknown. We investigated the influence of heat stress on
      metabolic and functional recovery after cardioplegic arrest, in a protocol
      mimicking clinical donor heart preservation. METHODS: Langendorff perfused rat
      hearts in control group (C, n = 6) and heat stressed (24 h prior to experiment)
      group (HS, n = 6) were subjected to 4 h of ischemia at 4 degrees C following
      cardioplegic arrest (St. Thomas' No. 1). 31P nuclear magnetic resonance
      spectroscopy was used to follow changes in ATP, phosphocreatine and inorganic
      phosphate concentrations during the pre-ischemic, ischemic and reperfusion
      periods. Myocardial adenine nucleotide levels in hearts at the end of experiments
      and purine catabolite release in coronary effluent during reperfusion, were
      evaluated using high performance liquid chromatography. Mechanical function in
      the pre-ischemic and reperfusion periods was evaluated using an intraventricular
      balloon. Western immunoblotting was used to quantitate HSP70 expression. RESULTS:
      Although baseline concentrations of ATP and phosphocreatine were similar in C and
      HS groups, the rate of high-energy phosphate depletion was attenuated during the
      early phase of ischemia in HS groups. On reperfusion, recovery of ATP was 10-20%
      greater in HS versus C groups; phosphocreatine levels also recovered better in
      the HS group, transiently reaching levels 40% higher in HS versus C groups. The
      concentrations of adenine nucleotides in hearts were significantly higher in the
      HS versus C groups. These changes were associated with an attenuation of total
      purine catabolite release in the coronary effluent in HS versus C groups. A
      significant improvement in relative recovery of developed pressure was shown in
      HS versus C groups in the post-ischemic periods. CONCLUSIONS: Heat stress causes
      beneficial changes in high-energy phosphate metabolism in the rat heart subjected
      to cardioplegic arrest and ischemia. Improved mechanical recovery in HS versus C
      groups was associated with a decreased rate of high-energy phosphate depletion
      and increased recovery of ATP and phosphocreatine levels during reperfusion.
      Changes in energy metabolism may play a role in the mechanism of cardioprotection
      by heat stress during prolonged hypothermic cardiac arrest. rights reserved.

PMID- 9641348
TI  - Influence of ageing on functional recovery and guanine nucleotide levels of the
      heart following cold cardioplegic arrest.
AB  - OBJECTIVE: The effect of age on metabolism and mechanical recovery of the heart
      after cardioplegic arrest is important, but remains a relatively unexplored
      subject. In this study, functional recovery and nucleotide levels were compared
      in the heart at different ages subjected to prolonged hypothermic cardioplegic
      arrest. METHODS: Three different age groups of rats: 1 (A); 4 (B); and 16 months
      (C) were perfused in working mode and subjected to cardioplegic arrest (St.
      Thomas' No. 1) and ischemia for 4 h at 4 degrees C, followed by reperfusion for
      35 min. Cardiac function (cardiac output and aortic pressure) was recorded before
      and after ischemia. Another series of hearts in all three age groups underwent 5
      min of normoxic perfusion to obtain pre-ischemic baseline metabolite
      concentrations. Hearts were freeze-clamped at the end of each experiment and used
      for determination of nucleotide and creatine metabolites by HPLC. RESULTS: The
      post-ischemic recovery (% of the pre-ischemic value) of the cardiac power was
      48.9 +/- 7.8% for group A, which was significantly higher than the functional
      recovery of group B (24.1 +/- 3.5%) or C (21.4 +/- 4.7%, P < 0.05, respectively).
      There was no difference in ATP or the total adenine nucleotide or creatine
      metabolite concentrations between the three age groups. In contrast, both GTP and
      the total guanine nucleotide concentration was highest in A (P < 0.05). Total
      guanylate pool was 1.52 +/- 0.10 1 micromol/g dry wt. in A, as compared to B
      (1.05 +/- 0.04) or C (1.12 +/- 0.04). NAD was significantly higher in B (4.1 +/-
      0.1. P < 0.05), when compared to A (3.6 +/- 0.1) and C (3.8 +/- 0.1). CONCLUSION:
      Best post-ischemic functional recovery after cardioplegic arrest was observed in
      the 1-month-old hearts (A) and was associated with highest guanine nucleotide
      concentration; preservation of guanine nucleotide pool in the youngest hearts may
      be an important mechanism for improved cardioprotection due to the important role
      of GTP in signalling pathways.

PMID- 9641349
TI  - Presentation of a pseudoaneurysm as a supravalvular aortic stenosis 20 years
      after aortic root reconstruction.
AB  - A 36-year-old patient was referred because of fatigue and decreased exercise
      tolerance 20 years after separate aortic valve replacement and aortic root
      reconstruction. The presence of a loud systolic ejection murmur and persistent
      left ventricular hypertrophy led to the diagnosis of severe supravalvular aortic
      flow obstruction by indirect compression of a large pseudoaneurysm.

PMID- 9641350
TI  - Composite graft replacement for treatment of ascending aortic aneurysms using
      original Bentall-DeBono procedure or its open button modification.

PMID- 9641351
TI  - VATS resection of oesophageal leiomyomas.

PMID- 9641352
TI  - Determinants of Clara cell protein (CC16) concentration in serum: a reassessment
      with two different immunoassays.
AB  - Clara cell protein (CC16) is a 16 kiloDalton protein secreted by Clara cells in
      the lining fluid of bronchiolar and bronchial epithelium. Recently, Nomori et
      al., using a nephelometric latex immunoassay, reported a strong correlation
      between serum CC16 (sCC16) and serum lipids as well as the body mass index (BMI)
      [Nomori H, Horio H, Takagi M Kobayashi Y, Hirabayashi Y. Clara cell protein
      correlation with hyperlipidemia. Chest 1996;110:680-4]. The same authors found
      higher values of sCC16 in males compared to females and did not detect any
      significant influence of tobacco smoking. Since these results are in disagreement
      with previous observations showing consistently a decrease of sCC16 in smokers
      and no influence of sex, we have reassessed in healthy subjects the determinants
      of sCC16 using two different assays: a particle counting-based latex immunoassay
      (LIA) using polyclonal antibodies and a fluorescence enzyme immunoassay (FEIA)
      using monoclonal antibodies. sCC16 was determined in a group of 52 female and 44
      male healthy subjects (age 18 to 66 years), including 35 smokers and 61
      nonsmokers. sCC16 measured by LIA and FEIA were well correlated (r = 0.92, n =
      96, P < 0.0001) with values (geometric mean and range) of 13.3 (5.2-34.5) and
      14.7 (4.1-53.1) microg/l, respectively. The determinants of sCC16 measured by
      both techniques were traced by stepwise regression analysis using as independent
      variables age, sex, smoking status, BMI or serum lipids (total cholesterol and
      triglycerides) and the glomerular filtration rate (GFR) estimated on the basis of
      serum creatinine or beta2-microglobulin. Only two significant determinants
      emerged: tobacco smoking which correlated negatively and the GFR which correlated
      positively with sCC16. No influence of serum lipids, BMI, age and sex on sCC16
      was detected. We think that an analytical interference with serum lipids explains
      the results by Nomori et al. which are not confirmed here by two independent
      techniques and are inconsistent with the current understanding of the
      physiopathology of the Clara cell and its main secretory product, CC16.

PMID- 9641353
TI  - Analysis of human primary bone cells by fluorescence activated cell scanning:
      methodological problems and preliminary results.
AB  - We describe the development of flowcytometrical methods to analyse human primary
      osteoblast-like cultures obtained from trabecular bone explants in comparison to
      the human osteosarcoma cell line HOS 58. Two antigens typical of osteoblasts were
      studied: bone alkaline phosphatase and collagen/procollagen I; the non-specific
      attachment protein fibronectin served as control. The morphology of all different
      antigens is shown by immunocytochemistry before flowcytometrical analysis. The
      establishment of flowcytometry is described in detail. While all antigens tested
      were nearly 100% positive in the HOS 58 cells in immunocytochemistry and
      flowcytometry, in primary osteoblast-like cells results varied widely between
      both methods. Cell permeabilisation before flowcytometry improved the homogeneity
      of results, probably by increasing the accessibility of the specific antibody to
      intracellular compartments. Though up to 80% of cells were lost during
      preparation the ratio of positive versus negative cells in specific experiment
      was not dependent on the cell recovery. Therefore, the cells finally analysed
      seemed to be representative of the total population.

PMID- 9641354
TI  - Clinical chemistry variables in normal elderly and healthy ambulatory
      populations: comparison with reference values.
AB  - Laboratory values of the most commonly assayed clinical chemistry variables were
      determined in selected elderly and healthy ambulatory populations. The upper and
      lower limits (2.5 and 97.5 fractiles) were compared with the adult reference
      values in use in university hospitals of Switzerland. The results suggest that
      conventional adult reference values can be used for most variables in the elderly
      and that these values are also useful in an ambulatory population.

PMID- 9641355
TI  - Amylase measurement with 2-chloro-4-nitrophenyl maltotrioside as substrate.
AB  - The use of 2-chloro-4-nitrophenyl maltotrioside (CNP-G3) as substrate to measure
      amylase (EC 3.2.1.1) activity in serum directly without the use of auxiliary
      enzymes was evaluated at two centres. The method was precise (within-run C.V. <
      2% and between-run C.V. < 3%), there was no lag phase, background absorbance was
      low and there were minimal effects of pH changes. When compared with a method
      which uses 4,6-ethylidene (G7)-p-nitrophenyl (G1)-alpha-D-maltoheptaoside (EPS
      G7) as substrate, the CNP-G3 method had greater sensitivity and longer reagent
      stability (21 days compared with 2 days at 4 degrees C). The activity measured
      with the CNP-G3 method correlated well with methods using either EPS-G7 and
      maltotetraose as substrates.

PMID- 9641356
TI  - Lack of correlation of free deoxypyridinoline excretion with Taq1 restriction
      length polymorphisms in the vitamin D receptor gene in males.
AB  - An association between allelic variants in the vitamin D receptor gene and bone
      mineral density has been previously described. A bimodal variation in the rate of
      bone resorption (as measured by urinary deoxypyridinoline excretion rate) has
      also been reported. We have recruited male volunteers, to minimise variation
      associated with ovarian function, to investigate a possible connection between
      these observations. Allelic variants in the vitamin D receptor gene were
      identified as Taq1 restriction fragment length polymorphisms. The ratio of
      variants TT:Tt:tt occurred with a frequency of 34%:47%:17%. Excretion rates of
      urinary free deoxypyridinoline, measured by immunoassay, were compared in age
      matched males from each genetic group. There were no significant differences
      based on the paired Student's t-test. Excretion rates declined with age (P =
      0.04) and the best fit model fits the same regression line to each group. Genetic
      variation in the vitamin D receptor is not linked with differences in bone
      resorption rates.

PMID- 9641357
TI  - Carbohydrate deficient transferrin in the assessment of alcohol misuse: absolute
      or relative measurements? A comparison of two methods with regard to total
      transferrin concentration.
AB  - Carbohydrate deficient transferrin (CDT) is now accepted as a potentially useful
      marker for the detection of alcohol misuse. It is not clear whether absolute
      values or values expressed relative to the total transferrin concentration
      provide the same diagnostic efficiency. CDT was measured in 35 patients with
      alcohol related liver disease, 35 subjects abusing alcohol without evidence of
      liver disease and 35 patients with chronic viral hepatitis using two commercial
      methods (CDTect and %CDT). To compare the methods, results were normalised by
      dividing the actual result by the upper limit of the reference range. Subtracting
      normalised %CDT results from the normalised CDTect results demonstrated a linear
      relationship between CDTect and total transferrin. This linear relationship could
      be abolished by calculating the CDTect/total transferrin ratio. The sensitivity
      of the methods was similar with CDTect (43 and 57%) being slightly superior to
      %CDT (40 and 46%). Specificity was similar (78%) for both methods. Calculation of
      the CDTect/total transferrin ratio improved the sensitivity and specificity
      slightly. The linear relationship between CDTect and total transferrin may
      produce misleading results in populations with a high prevalence of abnormal
      total transferrin concentrations and could cause difficulties in method
      comparisons unless taken into account.

PMID- 9641358
TI  - Troponin I, troponin T, CKMB-activity and CKMB-mass as markers for the detection
      of myocardial contusion in patients who experienced blunt trauma.
AB  - Myocardial contusion is an infrequent, but sometimes serious complication in
      patients who experienced deceleration (blunt) trauma. We investigated the
      assessment of the new cardiac markers troponin I (cTnI) and troponin T (cTnT) in
      relation to the conventional CKMB-activity, the CKMB-activity/CK-total ratio,
      CKMB-mass and the CKMB-mass/CK-total ratio for the detection of myocardial
      contusion in 89 patients with blunt trauma (38 patients with thoracic injuries
      and 51 patients without thoracic injuries). All parameters were analysed at
      admission (t1) and 24 h after admission (t2). For the patients with thoracic
      injuries, at t1 cTnI was elevated in three, and cTnT in four patients; at t2 both
      cTnI and cTnT were elevated in nine patients. At t1, eighteen to thirty patients
      had increased levels of the conventional parameters; at t2 this was true for six
      to thirty-five patients. For the patients without thoracic injuries all cTnI and
      cTnT levels were within the reference ranges at t1. At t2 one patient, who
      experienced an acute myocardial infarction, had elevated cTnI and cTnT levels. At
      t1, five to thirty-five patients had increased levels of the conventional
      parameters; at t2 this was true for four to forty-two patients. From this study
      we conclude that the conventional parameters are not useful for the detection of
      myocardial contusion in patients experiencing blunt trauma. The parameters cTnI
      and cTnT are equally accurate and more reliable for the selection of patients who
      require intensive cardiac monitoring. If at admission the cTnI or the cTnT levels
      are within the reference ranges, a second analysis after admission is necessary
      to reach a reliable conclusion concerning myocardial contusion as a result of
      trauma on basis of the troponin levels.

PMID- 9641359
TI  - Evaluation of the new automated ELISA Vidas Lp(a) assay. Comparison with an
      immunonephelemetric method.
AB  - Lipoprotein (a) [Lp(a)] is a lipoprotein which has a plasma concentration that is
      highly correlated with cardiovascular disease. In this study, the new Lp(a) assay
      for the Vitek Immuno-Diagnostic Assay System (VIDAS) developed by bioMerieux was
      evaluated. This method uses an enzyme linked fluorescent immunoassay (ELFIA)
      technique. Within-run and between-run reproducibility of the Vidass Lp(a) assay
      are characterized by coefficients of variation (CV) of 3 to 5.9% and 3.9 to 5.9%,
      respectively. Using analysis of variance, no statistical difference was shown
      between ELFIA and immunonephelometric assay (INA). When comparing results of the
      Vidas Lp(a) test with the INA, a highly significant correlation of r = 0.9708 and
      regression line equation y = 0.963x-0.037 was found. Interference of lipemia was
      studied: no influence was observed up to 12.3 mmol l(-1) triglycerides. No
      interference of haemoglobin was noted for Lp(a) > 0.20 g l(-1).
      Hyperbilirubinemia ( > 120 micromol l(-1)) led to results being underestimated
      for concentrations of Lp(a) which were < 0.20 g l(-1). No pre-analytical
      interference of citrate was measured but pre-analytical interference of EDTA was
      found. In conclusion, this new fully automated immunofluorimetric Lp(a) assay
      enables to the rapid, accurate and reliable determination of Lp(a) in blood
      samples.

PMID- 9641360
TI  - Autoantibodies to gangliosides in sera of atherosclerotic patients.
AB  - Using ELISA we studied the levels and clinical correlation of serum antibodies
      against gangliosides and 5-hydroxytryptamine (5-HT) in patients with
      atherosclerosis and clinical manifestations of cardiovascular disease. A range of
      70-80% of the patients showed higher titers of anti-GM3(L) and anti-5HT as
      compared to normal serum. The anti-GM3(L) antibodies appeared to be directed
      mainly against GM3 present in platelets and were much less reactive against GM3
      isolated from the aorta. We concluded that the antigens responsible for the
      elevated anti-GM3(L) and anti 5-HT levels in atherosclerotic sera are released by
      vessel-wall activated platelets. These results provide further evidence of on
      going autoimmune processes in atherosclerosis. The content of total sialic (TS)
      and lipid-bound sialic acid (LBS) was measured in sera of patients with IHD and
      of similar numbers of healthy donors. In the patient groups the average TS and
      LBS concentration was about 25% higher than in the control group. These changes
      appeared to be associated with higher degrees of protein sialylation and larger
      amounts of LDL in the patient sera than in those of healthy controls.

PMID- 9641361
TI  - Thrombolytic therapy does not change the release ratios of enzymatic and non
      enzymatic myocardial marker proteins.
AB  - Measurements of cardiac marker proteins in plasma from patients with acute
      myocardial infarction (AMI) have become important in the evaluation of
      recanalization therapy. The validity of this approach has however been
      questioned, because it was claimed that coronary reperfusion may increase the
      recovery in plasma of cardiac enzymes, such as creatine kinase (CK). In the
      present study, possible effects of thrombolytic therapy on the release of
      enzymatic and nonenzymatic marker proteins were investigated. Activities of CK
      and lactate dehydrogenase (LDH), and concentrations of myoglobin (Mb) and fatty
      acid-binding protein (FABP) were determined in serial plasma samples obtained
      from 50 patients with confirmed AMI, of whom 36 received thrombolytic therapy,
      and 14 did not. Treatment delay was 2.8+/-1.6 (mean+/-SD) h, and hospital delay
      in untreated patients was 2.7+/-1.8 h. Average infarct size, expressed in gram
      equivalents of heart muscle per litre of plasma (g-eq/l), varied between 5.5 and
      7.2 g-eq/l for the four marker proteins in patients treated with thrombolytic
      therapy, and between 4.6 and 6.4 g-eq/l in untreated patients, with a tendency to
      larger infarct sizes for Mb and FABP than for CK and LDH. Thrombolytic therapy,
      although significantly accelerating protein release rates, did not influence the
      release ratios. These results indicate that thrombolytic therapy has no
      significant effects on the recovery of cardiac marker proteins in plasma.

PMID- 9641362
TI  - Reference range of some enzymes and proteins in untimed overnight urine and their
      stability after freezing.

PMID- 9641363
TI  - Short Synacthen test: standard versus low dose in the evaluation of patients with
      pituitary diseases.

PMID- 9641364
TI  - Guidelines for the correct conduct of clinical research in surgery.
AB  - Clinical research may be either epidemiological or experimental. Epidemiological
      (observational) research includes cross-sectional, case-control, and cohort
      studies and draws attention to associations, which may or may not denote cause
      and effect. Experimental research may be explanatory, the purpose of which is to
      advance our knowledge of physiological or pathological events; or it may be
      pragmatic, the purpose of which is to influence our treatment of patients. All
      these types of clinical research have their own rules, but underlying the
      detailed rules are the universal ones of telling the truth and doing no harm.

PMID- 9641365
TI  - Hyperbaric oxygen in the treatment of Fournier's gangrene.
AB  - OBJECTIVE: To investigate the efficacy of operation, antibiotic treatment,
      hyperbaric oxygen, and surgical intensive care in the management of Fournier's
      gangrene. DESIGN: Retrospective study. SETTING: University hospital, Finland.
      SUBJECTS: 33 patients, most of them referred from other hospitals. INTERVENTION:
      Debridement, broad spectrum antibiotics, and hyperbaric oxygen (HBO) treatment at
      2.5 atmospheres absolute pressure. Excision of necrotic tissue and incisions in
      the affected areas. Urinary and faecal diversions when necessary. MAIN OUTCOME
      MEASURES: Morbidity and mortality. RESULTS: Only three patients died (9%).
      Hyperbaric oxygen reduced systemic toxicity, prevented extension of the
      necrotising infection, and increased demarcation, thereby improving the overall
      outcome. CONCLUSION: To reduce mortality and morbidity, effective treatment of
      Fournier's gangrene should be started promptly. Debridement and antibiotics
      combined with surgical intensive care must be started as soon as possible.
      Hyperbaric oxygen is both life and tissue saving. It is an important adjunct that
      prevents extension of necrosis and reduces systemic toxicity.

PMID- 9641366
TI  - Rapid increase in volume of the remnant after hemithyroidectomy does not
      correlate with serum concentration of thyroid stimulating hormone.
AB  - OBJECTIVE: To study the effect of postoperative thyroxine on the volume of the
      thyroid remnant after lobectomy for benign nontoxic goitre. DESIGN: Prospective,
      randomised study. SETTING: University hospital, Sweden. SUBJECTS: 50 consecutive
      patients who underwent lobectomy for benign non-toxic goitre. INTERVENTIONS:
      Patients were randomised postoperatively to take thyroxine 0.1 mg or placebo
      daily. MAIN OUTCOME MEASURES: The median volume of the remaining thyroid lobe
      measured by ultrasound. Serum concentrations of thyroxine, triiodothyronine (T3)
      and thyroid stimulating hormone (TSH) were measured preoperatively and 1, 3, 6,
      12 months postoperatively. RESULTS: The median volume of the remaining lobe had
      increased significantly compared with preoperatively by 1 month postoperatively
      by 30% in the thyroxine group and 25% in the placebo group (p < 0.01). The
      difference between the groups was not significant. After the first month the
      volume did not change significantly. In the thyroxine group, the TSH
      concentration was unchanged and the thyroxine concentration increased
      significantly throughout the study. In the placebo group there was a significant
      increase in TSH concentration and a significant decrease in that of thyroxine at
      all follow-up examinations. CONCLUSIONS: There is a significant increase in the
      volume of the remaining thyroid 1 month after lobectomy that persisted throughout
      the first year. Thyroxine given in a dose that kept the serum TSH concentration
      at the same level as preoperatively did not seem to influence volume changes;
      consequently we consider that these are caused by factors other than TSH.

PMID- 9641367
TI  - An "all comers" policy for ruptured abdominal aortic aneurysms: how can results
      be improved?
AB  - OBJECTIVE: To review our experience of a non-selective policy for the treatment
      of ruptured abdominal aortic aneurysm to see if the policy was justified, and to
      identify any preoperative risk factors that adversely influenced outcome. DESIGN:
      Retrospective study. SETTING: Teaching hospital, Republic of Ireland. SUBJECTS:
      258 patients admitted with abdominal aortic aneurysms between January 1982 and
      December 1993. INTERVENTIONS: Definitive surgical treatment. MAIN OUTCOME
      MEASURES: Morbidity, mortality, and risk factors. RESULTS: In-hospital mortality
      for all patients was 43% (110/258). Overall, women did worse than men (28/44,
      64%, died, compared with 96/214, 45%, p=0.03). The mortality among patients over
      the age of 80 (23/45, 51%) was not significantly different from that among
      younger patients (97/202, 48%). Blood pressure, platelet count, and haemoglobin
      concentration were all significantly lower preoperatively among those who died (p
      < 0.05). CONCLUSIONS: Age alone cannot be used to justify witholding definitive
      surgical treatment. Treatment should be aimed towards reversing haematological
      and haemodynamic abnormalities preoperatively to try to improve outcome.

PMID- 9641368
TI  - Cardiff repair of incisional hernia: a university hospital experience.
AB  - OBJECTIVE: To analyse our results of the "Cardiff' (far and near) repair in
      incisional hernias. DESIGN: Prospective study. SETTING: University hospital,
      Varanasi, India. SUBJECTS: 50 patients who presented with incisional hernias
      between January 1990 and December 1994. INTERVENTION: Interrupted far-and-near
      sutures inserted after excision of the sac. The contents were pushed into the
      abdomen and the peritoneum sutured with non-absorbable polypropylene (prolene).
      MAIN OUTCOME MEASURES: Early and late morbidity. Six patients developed
      postoperative complications (wound infection, n=3; flap necrosis, n=2; and wound
      sinus, n=1). No patient has been lost to follow up and there have been no signs
      of recurrence after a mean follow up of 52 months. CONCLUSION: The meticulous
      application of this simple surgical technique has low morbidity and is cost
      effective. We recommend it for small and medium size defects.

PMID- 9641369
TI  - Morgagni's hernia in infants and children.
AB  - OBJECTIVE: To report my experience of Morgagni's hernia in 4 infants and 1 child.
      DESIGN: Retrospective study. SETTING: Teaching hospital, Saudi Arabia. SUBJECTS:
      4 infants and 1 child with Morgagni's hernias, one of which was recurrent.
      INTERVENTIONS: Repair through an abdominal incision. MAIN OUTCOME MEASURES:
      Presentation, morbidity, and recurrence. RESULTS: 4 of the 5 cases presented with
      respiratory distress or pulmonary infection, or both; 1 presented with failure to
      thrive as well. 3 patients had associated anomalies (hypertrophic pyloric
      stenosis, malrotation of the gut, and left inguinal hernia; Down syndrome; and
      multiple Mongolian spots and umbilical hernia). The hernia was recognised on
      chest radiograph in all cases, and confirmed by barium studies in 3. All the
      hernias were repaired through an abdominal incision. There were no deaths and no
      early complications, but late complications included a recurrence and incisional
      hernia in 1 patient and midgut volvulus caused by associated anomalies in
      another. CONCLUSION: Outcome is usually influenced by associated anomalies and
      the seriousness of the effects of the hernia. Timely diagnosis and repair can
      improve outcome.

PMID- 9641370
TI  - Long term follow up of patients who underwent jejunoileal bypass for morbid
      obesity.
AB  - OBJECTIVE: To describe our long term results after jejunoileal (JI) bypass for
      morbid obesity. DESIGN: Retrospective study. SETTING: Teaching hospital, Denmark
      SUBJECTS: All 57 patients who underwent JI bypass for morbid obesity between
      January 1973 and December 1988. INTERVENTIONS: Type A and type B JI bypass. MAIN
      OUTCOME MEASURES: Weight loss, operative morbidity and mortality, and subjective
      evaluation of the results. RESULTS: Mean duration of follow up was 15.9 years
      (range 8-22). There were no operative or early postoperative deaths, but there
      were 7 late deaths (12%). 5 patients developed postoperative complications (9%),
      and 11 patients (19%) required reoperation for side effects or complications. The
      mean body mass index (BMI, kg/m2) was reduced from 47.5 (range 40-60) to 32
      (range 22-49) during the follow up period which corresponded to a weight loss of
      about 42 kg. Of the 39 patients who still had a JI bypass in 1994, nearly two
      thirds said that they were satisfied with the operation, though they nearly all
      had some side effects such as diarrhoea or intermittent abdominal pain.
      CONCLUSION: As complications of JI bypass can develop at any time, we suggest
      that all patients who have had the operation should be regularly followed up at
      special clinics so that complications can be diagnosed and treated as soon as
      possible.

PMID- 9641371
TI  - A survey of surgical treatment of gallstone disease and the diffusion of
      laparoscopic surgery in Sweden 1992-93.
AB  - OBJECTIVE: To study the diffusion of laparoscopic biliary surgery in Sweden, 1992
      93. DESIGN: A prospective survey of all biliary surgery for gallstone disease
      recorded for 8 weeks in 1992 and the same period in 1993. SETTING: All surgical
      departments in Sweden. SUBJECTS: A consecutive series of 1938 patients in 1992
      and 1748 patients in 1993. MAIN OUTCOME MEASURES: The changing indications,
      diffusion, morbidity, mortality, postoperative and hospital stay after
      laparoscopic cholecystectomy (LC) in Sweden in 1992 compared with 1993. RESULTS:
      Despite the spread of LC, the indications did not change between 1992 and 1993
      (p=0.31). The total number of cholecystectomies decreased from 1938 in 1992 to
      1748 in 1993. The overall percentage of laparoscopic cholecystectomies (LCs)
      increased from 74.7% to 81.2% (p <0.001) between 1992 and 1993. Postoperative
      morbidity and mortality after LC did not differ between 1992 and 1993, but the
      total morbidity was 9.0% in 1992 and 7.0% in 1993 (p=0.02). Mortality for all
      cholecystectomies did not change over the periods, being 0.6% in 1992 and 0.2% in
      1993 (p=0.07). The numbers of LCs done in any hospital were divided in two
      groups, 20 or fewer and 21-80. In the smaller group, the postoperative morbidity
      was 7.1% and in the larger group it was 7.0%, (p=0.9). The postoperative
      mortality was 0.1% in both groups. The postoperative and total hospital stays of
      all cholecystectomies decreased from 3.4 days in 1992 to 2.9 days in 1993
      (p=0.001) and from 5.0 in 1992 to 4.4 days in 1993 (p < 0.001), respectively. The
      postoperative and total hospital stays of LCs decreased from 2.0 in 1992 to 1.8
      days in 1993 (p=0.009) and from 3.3 in 1992 to 2.9 days in 1993 (p=0.007),
      respectively. CONCLUSION: Despite the introduction and diffusion of the new
      technology, LC, the indications for surgery did not change and the number of
      cholecystectomies did not increase from 1992 to 1993. The morbidity and mortality
      of LC and the mortality of all cholecystectomies were unchanged between 1992 and
      1993, but the morbidity for all cholecystectomies decreased. The number of LC or
      all cholecystectomies done in any particular hospital were not related to
      morbidity or to mortality.

PMID- 9641372
TI  - An experimental study on effects of monopolar diathermy on the bile ducts.
AB  - OBJECTIVE: To study the effects of monopolar diathermy on the bile ducts in pigs.
      DESIGN: Experimental study. SETTING: University hospital, Norway. MATERIAL: 18
      pigs. INTERVENTIONS: Laparotomy, application of diathermy at standard sites along
      the cystic duct, the bile ducts, and a cystic duct containing a metal clip, 3 to
      12 times of 5 seconds' duration at each site. Temperature was subsequently
      recorded at standard measurement points on the bile ducts. Twelve pigs were
      killed after three weeks for assessment of the bile ducts at necropsy. MAIN
      OUTCOME MEASUREMENTS: Increase in temperature in the bile duct walls and late
      changes in the bile ducts. RESULTS: Temperature increased by 4-6 degrees C during
      6 of 330 diathermy applications along the cystic duct, by 4-18 degrees C in 8 of
      126 applications along the common bile duct, and by 4-11 degrees C at the clip in
      9 of 54 applications. There were no macroscopic or microscopic changes in the
      bile ducts. CONCLUSION: Monopolar diathermy induced unexpected distant increases
      in the temperature of the bile duct walls and at a clip on the cystic duct
      probably because diathermy current energy was distributed along channels of high
      current conductivity.

PMID- 9641373
TI  - Full thickness resection of radiation-induced ulcers of the chest wall:
      reconstruction with absorbable implants, pedicled omentoplasty, and split skin
      graft.

PMID- 9641374
TI  - Pancreatoblastoma in an adolescent girl: case report and review of 26 Japanese
      cases.

PMID- 9641375
TI  - Spontaneous rupture of the oesophagus in an adolescent with type IV Ehlers-Danlos
      syndrome. Ehlers-Danlos and spontaneous oesophageal rupture.

PMID- 9641376
TI  - Thoracoscopic upper thoracic sympathectomy for primary palmar hyperhidrosis--the
      combined paediatric, adolescents and adult experience.
AB  - OBJECTIVE: To present our experience, over the past 4 years, of thoracoscopic
      upper thoracic sympathectomy in patients with primary palmar hyperhidrosis.
      DESIGN: Retrospective study. SETTING: University hospital, Israel. SUBJECTS: 402
      thoracoscopic upper thoracic sympathectomies in 223 patients over a period of 4
      years. INTERVENTIONS: Thoracoscopic ablation of ganglia and severing of the
      sympathetic chain at the level of T2 and T3. 142 patients underwent bilateral
      simultaneous sympathectomy, 37 had bilateral non-simultaneous sympathectomy and
      44 had unilateral sympathectomy. RESULTS: 220 patients (98.7%) had an uneventful
      postoperative course and were discharged the following day. Three patients with
      residual pneumothorax required intercostal drainage and were discharged on the
      third postoperative day. 219 patients (98.2%) were completely satisfied, having
      immediate and permanent relief of palmar sweating. Four patients were
      dissatisfied. CONCLUSION: The thoracoscopic approach to the upper thoracic
      sympathectomy is at present the procedure of choice. Early operation for severe
      palmar hyperhidrosis is indicated to save a child many years of frustration and
      discomfort.

PMID- 9641377
TI  - Improvements in video-endoscopic sympathicotomy for the treatment of palmar,
      axillary, facial, and palmar-plantar hyperhidrosis.
AB  - Video-endoscopic sympathicotomy for the treatment of palmar, axillary, facial and
      palmar-plantar hyperhidrosis was modified as to the type of surgical access and
      the level of incision in the sympathetic chain and communicating rami, depending
      on the clinical indications. Under general anaesthesia, using a single lumen
      endotracheal tube, the patient is put in lateral decubitus and pneumothorax is
      induced. The patient is then placed in ventral decubitus, with the head elevated,
      to make two punctures in the posterior axillary line, at the level of the 4th and
      7th intercostal spaces, to introduce two ports of 5 and 10 mm in size,
      respectively. The sympathetic chain and the communicating rami are viewed and
      severed, according to the indications, at different levels to treat palmar,
      axillary, facial and palmar-plantar hyperhidrosis and combinations of the above.
      The operation is performed on both sides of the thorax during the same period of
      anaesthesia. One hundred-forty patients (280 procedures) have been operated on
      from 1993 to 1997 using this technique. All were operated on as outpatients. Our
      results are: 100% of those with facial and palmar hyperhidrosis and 96% of those
      with axillar hyperhidrosis were cured, and 94% with plantar hyperhidrosis were
      relieved from 50 to 100%, with the follow-up of between one and 47 months.

PMID- 9641378
TI  - Thoracoscopic T2-sympathetic block by clipping--a better and reversible operation
      for treatment of hyperhidrosis palmaris: experience with 326 cases.
AB  - Although thoracoscopic sympathectomy or sympathicotomy is the best treatment for
      hyperhidrosis palmaris, a new approach of clipping only without transection of T2
      sympathetic trunk is just as effective. Aside from the guaranteed cure of
      hyperhidrosis, this new method has fewer complications and has the advantage of
      recovery of the sympathetic tone in the hands if the procedure is reversed by the
      removal of the clips. Between March 18 and September 30 of 1996, 326 patients
      (190 female and 136 male with a mean age of 20.5 years) underwent thoracoscopic
      T2-sympathetic block by clipping to treat hyperhidrosis. Good results and few
      complications were noted during follow up six months to one year postoperatively.
      Five of the 326 patients, all female, had the operation reversed because of
      intolerable compensatory sweating. Three recovered from the compensatory sweating
      within two months and had less palmar sweating than before their sympathetic
      block; the fourth achieved relief of compensatory sweating after nine months, and
      the fifth reported no improvement.

PMID- 9641379
TI  - Secondary sympathetic chain reconstruction after endoscopic thoracic
      sympathicotomy.
AB  - Thoracoscopic sympathicotomy by electrocautery is an irreversible procedure. Thus
      the indications must be meticulously considered before the final decision to
      operate is taken by both the surgeon and the patient. All possible side effects
      should be dealt with and written informed consent required. A case of an open
      nerve reconstruction of the divided sympathetic chains is presented. One year
      after the reconstruction the patient reported subjective relief of the
      compensatory oversweating and restoration of sweating in the face and the armpit.
      Reversible methods like clipping the sympathetic chain should be considered
      whenever feasible instead of the irreversible electrocoagulation of the
      sympathetic chain.

PMID- 9641380
TI  - Thoracoscopic sympathectomy: the U.S. experience.
AB  - OBJECTIVE: 48 patients underwent TSSYM. Charts of patients undergoing
      thoracoscopy were reviewed to assess the safety and efficacy of thoracoscopic
      sympathectomy (TSSYM). DESIGN: A retrospective review was undertaken at four
      United States medical centers. RESULTS: TSSYM was performed for reflex
      sympathetic dystrophy in 27 patients, hyperhydrosis palmaris in 15 patients, and
      Raynaud's upper extremity ischemia and splanchnic pain in 2 patients each.
      Anesthesia with one lung ventilation was used. 2.9 ports were used per patient
      and 0.8 chest tubes were placed per patient. All patients underwent resection of
      the sympathetic chain, usually with a clip along the bottom of the resected
      chain. Laser, electro-ablation and electroresection were not used by any of the
      surgeons in his series. The mean length of hospital stay was 1.8 days.
      CONCLUSIONS: TSSYM is a safe and effective technique for treatment of a variety
      of thoracic disorders.

PMID- 9641381
TI  - The Boras experience of endoscopic thoracic sympathicotomy for palmar, axillary,
      facial hyperhidrosis and facial blushing.
AB  - OBJECTIVE: To study the outcome of endoscopic thoracic sympaticotomy (ETS) for
      palmar, axillary, facial hyperhidrosis and facial blushing. SUBJECTS: 1152
      patients, 59% women and 41% men. INTERVENTION: ETS was performed by transection
      of the sympathetic chain where it overlies the second and third rib. The nerve
      was divided also over the fourth rib in patients with axillary hyperhidrosis.
      Questionnaires were sent to all patients. MAIN OUTCOME MEASURES: The effect of
      surgery was assessed by a 10 grad visual analogue scale (VAS) by the patients.
      The results were divided into effect rate (the effect on the symptom) and overall
      satisfaction rate, taking into account any side effects and complications apart
      from the effect. RESULTS: The response rate was 90%. The mean follow up time,
      effect rate and overall satisfaction rate were: 38 months for palmar
      hyperhidrosis, 99.4% and 87%; 26 months for axillary hyperhidrosis, 94.5% and
      68%; 31 months for facial hyperhidrosis, 97% and 76%; 8 months for facial
      blushing, 96% and 85%. CONCLUSION: ETS is a very effective procedure in palmar,
      axillary and facial hyperhidrosis and facial blushing. The overall satisfaction
      rate is very good for palmar hyperhidrosis and facial blushing, not equally good
      but acceptable for facial hyperhidrosis. The lower satisfaction rate in patients
      with axillary hyperhidrosis makes this a questionable indication for ETS.

PMID- 9641382
TI  - Treatment of social phobia by endoscopic thoracic sympathicotomy.
AB  - OBJECTIVE: To analyse the severity of various symptoms and the developmental life
      history in social phobia. To estimate the value of ETS in the treatment of
      chronic social phobia. DESIGN: Prospective study. SETTING: Clinic for
      Psychoneurology and Surgery in Tampere, Finland. SUBJECTS: Consecutive series of
      patients (n = 51). INTERVENTIONS: Endoscopic thoracic sympathicotomy. MAIN
      OUTCOME MEASURES: Qualitative ideographic inquiry. Questionnaire of the symptom
      severity using visual analogue scale. RESULTS: The life history included mental
      and physical abuse in 61%, paternal alcoholism in 26%. Four family subtypes were
      named: quarrelsome, cruel, alcoholic, and perfectionist. The pathognomonic
      symptoms of social phobia: hyperhidrosis, palpitation, blushing, tremor, and
      anxiety, were all highly significantly (p < 0.001) alleviated by ETS. 88% of the
      patients were satisfied with the result. There were no complications. CONCLUSION:
      ETS seems a promising alternative to conservative therapy for social phobia.

PMID- 9641383
TI  - Complications of endoscopic sympathectomy.
AB  - Four cases are presented in which complications occurred during or after thoracic
      endoscopic sympathectomy (TES). In one patient inappropriate TES resulted in
      disabling hyperhidrosis. In one patient laceration of the subclavian artery
      required major surgery. In two cases intraoperative cerebral damage occurred.
      Training in TES is essential.

PMID- 9641384
TI  - The haemodynamic effect of thoracoscopic cardiac sympathectomy.
AB  - A patient with angina pectoris who had been successfully treated by thoracoscopic
      cardiac sympathectomy was scheduled to have scalp debridement under general
      anaesthesia for a scald burn. There were haemodynamic changes during and after
      the operation including anaesthetic induction, endotracheal intubation,
      maintenance, and early recovery period. The sympathetic denervated heart showed
      little chronotropic response to anaesthetic and surgical stimulation. On the
      contrary, the parasympathetic response was predominant. An episode of severe
      bradycardia occurred during endotracheal suctioning prior to extubation. The
      haemodynamic response to cardiac sympathetic denervation corresponded to the
      efferent effect of beta-receptor blockade

PMID- 9641385
TI  - Quality of life after transthoracic endoscopic sympathectomy for upper limb
      hyperhidrosis.
AB  - OBJECTIVE: To assess the outcome after transthoracic endoscopic sympathectomy
      (TES) for upper limb hyperhidrosis. DESIGN: Prospective cohort study. SETTING:
      District general hospital. SUBJECTS: Consecutive patients undergoing TES for
      upper limb hyperhidrosis over a fifteen month period. INTERVENTIONS: One-stage
      bilateral TES. MAIN OUTCOME MEASURES: Change in quality of life as shown by the
      Short Form-36 health assessment questionnaire. RESULTS: Sixteen patients (11
      women and 5 men, median age 26 years) underwent operation without complications.
      At median follow-up of 6.2 months, symptomatic improvement was found in 26 of 32
      limbs treated (82%). Truncal compensatory hyperhidrosis was reported by 13
      patients but was severe in only three. There were significant improvements in
      social function (p = 0.01) and mental health (p = 0.025) as assessed by the SF
      36. CONCLUSION: Despite a high incidence of compensatory hyperhidrosis, TES
      improved both the symptoms and overall quality of life in patients with upper
      limb hyperhidrosis.

PMID- 9641386
TI  - Long-term results of 630 thoracoscopic sympathicotomies for primary
      hyperhidrosis: the Vienna experience.
AB  - OBJECTIVE: To evaluate of the results of thoracoscopic sympathicotomy for upper
      limb hyperhidrosis with a median observation period of more than 15 years.
      DESIGN: Retrospective clinical observation study. SETTING: University-affiliated
      tertiary referral centre. SUBJECTS: 630 consecutive operations in 352 patients
      (median age 30.1 yrs) for primary palmar (68%), axillary (12.7%) and combined
      hyperhidrosis (19.3%). INTERVENTIONS: Thoracoscopic sympathicotomy from below T1
      to T4 including the fibres of Kuntz using electrocautery through single site
      access. MAIN OUTCOME MEASURES: Perioperative success and complication rates (all
      patients); long-term follow-up by a questionnaire and/or clinical examination
      (83.3% of patients) after a median period of 16 yrs. Calculation of statistical
      significance of differences between groups with c2-test. RESULTS: 67.8% of
      patients were fully satisfied, 25.7% were partially satisfied and would again
      agree to the operation. In 93% the procedure cured hyperhidrosis permanently.
      Compensatory and gustatory sweating was observed in 67% and 47% of cases,
      respectively. Overall success was significantly (p < 0.001) lower in the group
      with axillary hyperhidrosis. Main complications: drainage for pneumothorax 1.3%,
      Horner's syndrome in 3.8%, subcutaneous emphysema 2.1%. CONCLUSION: Thoracoscopic
      sympathicotomy proved to be highly effective even after long-term follow-up.
      Compensatory sweating impairs patients' satisfaction in some cases.

PMID- 9641387
TI  - Value of Doppler sonography in the assessment of patients with Caroli's disease.
AB  - PURPOSE: We examined the intracystic flow pattern and portal hemodynamics with
      Doppler sonography in patients with Caroli's disease. METHODS: Sonographic
      characteristics and portal hemodynamics were studied by color Doppler sonography
      and spectral analysis in 5 patients (4 children and 1 adult) with Caroli's
      disease using high-frequency transducers. Caroli's disease was associated with
      infantile polycystic kidney disease in 4 patients and congenital hepatic fibrosis
      in 2 patients. Four patients had no clinical or imaging evidence of portal
      hypertension. The adult patient had congenital hepatic fibrosis and portal
      hypertension. RESULTS: Color Doppler sonograms and spectral analyses disclosed
      distinctive hepatic arterial and portal venous flow within the fibrovascular
      projections in the bile ducts of all the children. The adult with advanced portal
      hypertension presented with a no-flow state in the intracavitary part of the
      portal vein and a strong arterial signal related to disturbed hemodynamics in the
      arterialized liver. CONCLUSIONS: The fact that portal hemodynamics change over
      time should be taken into account when Doppler assessment of Caroli's disease is
      attempted. Doppler sonographic monitoring of the portal system to indirectly
      diagnose and follow the progression of so-called congenital hepatic fibrosis may
      be an effective alternative to liver biopsy.

PMID- 9641388
TI  - Sonography of gallbladder abnormalities in acromegaly patients following
      octreotide and ursodiol therapy: incidence and time course.
AB  - PURPOSE: We studied the effects of octreotide and ursodiol on the gallbladders of
      patients with acromegaly. METHODS: We performed gallbladder sonography in
      patients with acromegaly at various intervals during treatment. Group I (18
      patients) was treated with subcutaneous injections of the somatostatin analogue
      octreotide. Group II (10 patients) was treated with ursodiol while receiving
      octreotide therapy. RESULTS: Seventy-eight percent of patients receiving
      octreotide developed gallbladder abnormalities: sludge in 72% (13/18) and calculi
      in 39% (7/18). Ursodiol reversed the gallbladder abnormalities in 7 of 10
      patients. CONCLUSIONS: A majority of patients receiving octreotide develop
      gallbladder abnormalities. Ursodiol appears to reverse the abnormalities in most
      cases.

PMID- 9641389
TI  - Relationships between echo level and histologic characteristics in small
      hepatocellular carcinomas.
AB  - PURPOSE: The relationships between ultrasound echo level and histologic
      characteristics of hepatocellular carcinomas (HCCs) of 2 cm or less in diameter
      were studied. METHODS: The apparent echo level and frequency-dependent
      attenuation from the abdominal wall to the tumor and surrounding liver parenchyma
      were quantitated on B-mode images using diagnostic ultrasound equipment. The
      inherent echo level corrected by the frequency-dependent attenuation was used in
      this study. Histologic specimens were collected by sonographically guided small
      gauge core-needle biopsy. Increase in deposition of fat and changes in cellular
      density and in connective tissue density were evaluated histologically. RESULTS:
      From the quantitative comparison of echo levels and histologic characteristics,
      it was evident that the deposition of fat caused an increase in echo levels. A
      reduction in connective tissue density resulted in a decrease in echo levels in
      hypoechoic HCCs, which had no or little fat deposition. CONCLUSIONS: The
      estimation of echo level in small HCCs may be useful in predicting the tumors'
      histologic characteristics.

PMID- 9641390
TI  - Sonographic appearances of small hepatic nodules without tumor stain on contrast
      enhanced computed tomography and angiography.
AB  - PURPOSE: We report the sonographic appearances and pathologic findings for
      hepatic nodules 2 cm or smaller that were detected by sonography but that did not
      produce a tumor stain on constrast-enhanced helical CT or digital subtraction
      angiography. METHODS: Sixty-six nodules 2 cm or less were found by sonography in
      39 patients. Sonographically guided needle biopsies were done on all lesions.
      RESULTS: Twenty-seven nodules were benign nodules, 9 were borderline lesions, and
      30 were hepatocellular carcinomas. Benign nodules were significantly smaller than
      hepatocellular carcinomas (mean size, 1.0 cm versus 1.4 cm, respectively; p
      <0.00001). Nodules 1 cm or smaller were more likely to be diagnosed as benign
      nodules (68%) than as either of the other types (32%; p = 0.01). A significantly
      greater percentage of hepatocellular carcinomas showed a heterogeneous pattern
      (64%) on sonography compared with benign nodules (25%) and borderline lesions
      (11%; p = 0.04). In nodules 1 cm or smaller, a homogeneous pattern (68%) was more
      common than a heterogeneous pattern (32%; p = 0.01). CONCLUSIONS: The nature of
      small hepatic nodules cannot be determined with sonography. Thus, biopsy remains
      the only technique for obtaining a definitive diagnosis.

PMID- 9641391
TI  - Sonographic findings in noncirrhotic portal fibrosis.
AB  - PURPOSE: The aim of this study was to evaluate the sonographic appearances of
      noncirrhotic portal fibrosis (NCPF). METHODS: Between 1983 and 1996, 12 patients
      between the ages of 16 and 60 years were diagnosed with NCPF on the basis of
      medical history and clinical, imaging, and biopsy findings. RESULTS: Sonograms
      for all patients showed hyperechoic bands surrounding the portal vein branches,
      which were separated from adjacent liver parenchyma by a hypoechoic stripe. All
      liver biopsy specimens showed nonspecific changes and no cirrhosis. Histologic
      findings included fibrosis and some obliteration of the intrahepatic portal
      veins. CONCLUSIONS: If sonography of the liver shows increased echogenicity of
      the walls of the portal vessels with a hypoechoic stripe between the wall and the
      adjacent liver parenchyma in a patient who has portal hypertension and normal
      liver function tests, NCPF should be considered.

PMID- 9641392
TI  - Fetal hydrops in the first trimester associated with maternal parvovirus
      infection.
AB  - We present a case of fetal hydrops associated with maternal parvovirus infection
      during the first trimester of pregnancy that sonographically mimicked findings
      associated with fetal aneuploidy. The transabdominal sonograms of this fetus at
      12.9 weeks' gestational age were consistent with increased nuchal translucency
      thickness. Transvaginal sonographic evaluation of the fetus showed generalized
      subcutaneous sonolucency suggestive of early fetal hydrops. An etiologic
      evaluation identified serologic evidence of recent maternal parvovirus infection
      and a normal karyotype. The pregnancy ended in fetal demise. Our findings suggest
      that visualization of nuchal translucency thickening in the first trimester
      should prompt a complete sonographic evaluation for fetal hydrops, which, if
      identified, should lead to serologic evaluation for parvovirus infection.

PMID- 9641393
TI  - Cervical varices: an unusual etiology for third-trimester bleeding.
AB  - We report an unusual etiology for third-trimester bleeding. A pregnant patient
      underwent sonographic evaluation after presenting in the third trimester with
      uterine contractions and bleeding per the vagina. Massive cervical varices were
      identified on prenatal sonography as the cause of the bleeding and resulted in
      cesarean delivery and gravid hysterectomy. Cervical varices may result in
      significant maternal morbidity despite prenatal diagnosis.

PMID- 9641394
TI  - Intra-abdominal lymphangioma in a newborn.
AB  - We report the case of a male newborn infant with an intra-abdominal cavernous
      lymphangioma that produced acute abdominal symptoms. Sonography showed a cystic
      mass with thin septations, which caused intestinal obstruction and stenosis of
      the iliac artery. The histologic findings after surgical resection reflected the
      sonographic appearance of the mass. The differential diagnosis of cystic
      abdominal lesions is discussed. Sonography is the preferred method of diagnosis.

PMID- 9641395
TI  - Duplicate origin of left vertebral artery with thrombosis at the origin: color
      Doppler sonography and CT angiography findings.
AB  - We describe a rare case of vertebral artery duplication in a patient with
      vertigo, weakness, and nausea. A color Doppler examination revealed a duplicate
      origin of the left vertebral artery and a hyperechoic thrombus at the origin of 1
      of the duplicated arteries. CT angiography of the lower neck area demonstrated
      duplicated vertebral arteries on the left side. MR angiography of the
      vertebrobasilar system did not show duplication, indicating that the duplicated
      vertebral arteries fused at a level higher than C2.

PMID- 9641396
TI  - Segmental hemorrhagic infarction of testis associated with epididymitis.
AB  - Testicular infarction is most commonly associated with acute testicular torsion.
      We present the sonographic findings in a case of segmental testicular infarction
      associated with epididymitis. The gray-scale abnormalities included a round, well
      defined, hypoechoic intratesticular mass and heterogeneity and enlargement of the
      epididymis. Color Doppler sonography demonstrated only minimal blood flow in the
      intratesticular mass and increased flow in the epididymis. Recognition of acute
      testicular segmental infarction as a complication of epididymitis may prevent
      unnecessary orchiectomy.

PMID- 9641397
TI  - Localized painful giant-cell thyroiditis without inflammatory signs in a
      euthyroid patient followed by serial sonography.
AB  - We describe a patient with localized painful giant-cell thyroiditis. A 45-year
      old woman noticed a tender lump in the left side of the neck. Sonography of the
      thyroid revealed diffuse swelling of the left lobe with irregular hypoechoic
      areas. Three months later, the tender swelling subsided, and the hypoechoic areas
      disappeared without any treatment. There were never any systemic signs of
      inflammation or thyroid dysfunction. Atypical localized subacute thyroiditis was
      considered to be the most probable diagnosis based on fine-needle aspiration
      cytology and serial sonography. Serial sonographic evaluations are useful to
      avoid unnecessary surgery.

PMID- 9641398
TI  - Effects of active noise reduction on noise levels at the tympanic membrane.
AB  - BACKGROUND: Active noise reduction (ANR) is an electronic system that works by
      continuous sampling of noise inside the earshell of the headset with a small
      microphone. This signal is inverted in phase through the headset speaker, thus
      reducing noise levels by destructive interference of the acoustic field. The
      system provides good low-frequency noise attenuation, but aircrew differ in their
      subjective opinion of ANR. The present study is an attempt to provide an
      objective assessment of the effect of ANR on noise levels at the tympanic
      membrane. METHODS: There were 7 subjects with normal ears who were placed in an
      environment of recorded noise from a BO-105 helicopter. A microphone probe was
      inserted to within 5 mm of the tympanic membrane of each subject's right ear.
      Noise levels in the ear were measured without a headset and with two different
      ANR headsets. Measurements were performed with and without the ANR system on, and
      with and without white noise through the headset communication system. The white
      noise was used to simulate aircraft communication noise. RESULTS: The two
      headsets tested had differing levels of passive and active attenuation. The ANR
      system produced a substantial low-frequency attenuation. However, noise levels in
      the mid frequencies increased somewhat when the ANR system was switched on. This
      effect was augmented when white noise in the communications system was
      introduced, particularly for one of the two headsets. Low-frequency noise
      attenuation of ANR systems is substantial, but an increased mid- and high
      frequency noise level caused by the ANR may affect both communication and overall
      noise levels. Our data provide advice on what factors should be taken into
      account when ANR is evaluated for use in an aviation operational environment.

PMID- 9641399
TI  - Auditory event-related potentials and reaction time during decompression from
      hyperbaric trimix conditions.
AB  - BACKGROUND: Auditory event-related potentials (ERP) and sensomotor reaction time
      (RT) were investigated in divers during decompression from hyperbaric trimix
      conditions in order to assess the auditory information processing of the divers.
      METHODS: Two passive series, 30 low (800 Hz) and 30 high (1200 Hz) tones were
      presented as well as one simple reaction task (SRT) and one choice reaction task
      (CRT) series. In both task series, the subjects were instructed to press the
      button as quickly as possible with the right-hand thumb after a low tone was
      heard. The individual analyses of the decompression period ERPs and RT data were
      compared with the pre-diving results for the series. RESULTS: Despite the
      interindividual differences, the sensomotor reactions were retarded during the
      decompression period, most clearly in the CRT. A prolongation of the N2 and P3
      latency in this series gives grounds to accept that a cognitive slowing takes
      part in the longer reaction times during decompression. The slowing of the
      auditory information processing during decompression manifests with task
      manipulation difficulties.

PMID- 9641400
TI  - Intrasynaptosomal free calcium and nitric oxide metabolism in central nervous
      system oxygen toxicity.
AB  - BACKGROUND: Central nervous system (CNS) oxygen (O2) toxicity is complex, and the
      etiology of its most severe manifestation, O2 convulsions, is yet to be
      determined. A role for nitric oxide (NO) has been proposed, although recent data
      have indicated that NO is synthesized from L-arginine by an enzyme, NO synthase
      (NOS). The enzyme is dependent on free calcium (Ca2+) concentration, therefore
      increases in intracellular Ca2+ may constitute the physiological and
      pathophysiological mechanisms for stimulating the synthesis of NO. METHODS: In
      this study, the intrasynaptosomal free calcium concentration ([Ca2+]i) was
      measured by the fluorescence of fura-2/AM, and cGMP (as an indirect marker of NO
      levels) was by radioimmunoassay (RIA) in the rat hippocampus after hyperbaric
      oxygen (HBO) exposure. We also investigated the effects of daurisoline (DSL,
      calcium channel blocker) and N-nitro-L-arginine (LNNA, NOS inhibitor) on the
      above biochemical parameters and the development of oxygen toxicity. RESULTS: The
      results show that when the rats were exposed to HBO at 0.5 MPa the
      intrasynaptosomal Ca2+ and cGMP levels increased by two and three times,
      respectively, whereas with the use of DSL prior to HBO, the accumulation of
      [Ca2+]i and cGMP dropped to 56% and 60%, correspondingly. In the rats medicated
      with LNNA prior to HBO. [Ca2+]i and cGMP levels dropped to 70% and 36% of the HBO
      group. At the same time, the appearance of CNS oxygen toxicity was delayed and
      the survival rate increased. The protective effects of LNNA were reversed by L
      arginine pretreatment. These findings suggest that the neuronal Ca2+ overload
      during HBO exposure is a major factor in the pathogenesis of CNS O2 toxicity, and
      cGMP-NO pathways may be directly involved in HBO-induced seizures.

PMID- 9641401
TI  - Subject's perceptions of the crew interaction dynamics under prolonged isolation.
AB  - BACKGROUND: The interactions of individuals participating in space simulation
      studies can give us valuable information about ways that space crew members
      relate with one another. A promising method of investigating such interactions is
      based on the Kelly repertory grid technique. HYPOTHESES: We predicted that in a
      space simulation crew: 1) one's personal self-concept would become closer to
      concepts about other crew members in a cohesive crew, and vice-versa, and 2) the
      similarity of one's ego images in the past, present and future influences that
      person's position in the group. METHOD: Crews from two isolation studies lasting
      135 and 90 days at the Institute for Biomedical Problems in Moscow were evaluated
      using a modification of the Kelly repertory grid technique. Members assessed each
      other on a monthly basis and during off-nominal simulated docking periods.
      RESULTS: During both isolations, crew members were unsuccessful in making their
      personal self-concepts move closer to their concepts about fellow crew members.
      Crew disintegration resulted, with one member becoming an outsider whose
      personality was characterized by a disintegrated ego-image and an infantile type
      of the present ego. CONCLUSIONS: In small isolated groups, failure to make
      personal self-concepts become more like concepts about other crew members can
      lead to group disintegration and tension and can result in the appearance of an
      outsider who has a disintegrated ego-image and an infantile present ego.

PMID- 9641402
TI  - Overtraining parameters in special military units.
AB  - BACKGROUND: Previous studies have shown the diagnostic relevance of the so-called
      free testosterone/cortisol ratio (FTCR). A condition of overtraining might indeed
      exist in an athlete when at least one of the two following criteria are observed:
      a) a FTCR value lower than 0.00035 (FT in nmol x L(-1) and C in micromol x L(
      1)); and b) a decrease in the FTCR of 30% or more. On the other hand, no previous
      research has studied the incidence of overtraining in special military units as a
      result of their demanding training programs. HYPOTHESIS: A percentage of recruits
      of the Spanish special military Unit, "Grupo de Operaciones Especiales," (GOES)
      might be overtrained. It was the purpose of our study to analyze the effects on
      the FTCR of an intense physical training program performed by recruits of the
      GOES. METHODS: Before (PRE) and after (POST) an 8-wk training program,
      respectively, the following measurements were made in 42 recruits of the GOES:
      hematological and hormonal parameters (FTCR), aerobic and anaerobic tests, and
      strength and power tests. RESULTS: A high incidence (10 subjects, 23.8% of total)
      of overtraining existed among conscripts, as determined by the absolute criterium
      of a decline in the FCTR of 30% or more when comparing PRE and POST values.
      Additionally, overtraining was associated with a decrease in performance (i.e.,
      isometric strength, vertical jump, Wingate tests). CONCLUSIONS: In addition to
      some conventional measurements of performance, the FTCR might be used to monitor
      exercise training in military units, in order to prevent overtraining.

PMID- 9641403
TI  - Flight performance effects of thermal stress and two aviator uniforms in a UH-60
      helicopter simulator.
AB  - The effects on flight performance of the four combinations of an unencumbered
      mission oriented protective posture (MOPP) aviator battle dress uniform (ABDU)
      and encumbered MOPP4 over ABDU flight ensemble in cool (70 degrees F or 21.1
      degrees C, 50% relative humidity [RH]) and hot (100 degrees F or 37.8 degrees C,
      50% RH) UH-60 simulator cockpit conditions were evaluated with a repeated
      measures, 2 x 2 factorial study using nine crews. The encumbered MOPP4 uniform
      had the most frequent adverse effect on flight performance followed by heat
      stress, with less frequent effects from the combination or interaction of these
      two factors. This study confirmed that heat stress and wearing an encumbered U.S.
      Army MOPP4 flight uniform significantly reduced endurance and flight performance
      in a UH-60 simulator.

PMID- 9641405
TI  - Effects of hypergravity on optokinetic after-nystagmus and perceived direction of
      optokinetic stimulation.
AB  - BACKGROUND: Previous observations made in parabolic flight and centrifuge studies
      have shown the presence of a vertical nystagmus (Lz-nystagmus) induced by changes
      in gravitoinertial forces, and its interaction with oculomotor reflexes.
      HYPOTHESIS: This Lz-nystagmus is also responsible for the changes in optokinetic
      after-nystagmus (OKAN) and the subjective perception of optokinetic stimulation
      direction during hypergravity. METHODS: OKAN was recorded during the 1.8-g phase
      of parabolic flight after exposure to horizontal or vertical optokinetic
      stimulation during the preceding 1.0-g or 0-g phases. Changes in the apparent
      direction of image motion in subjects presented with an optokinetic stimulus were
      investigated in another experiment where longer exposure to hypergravity was
      generated by flying an airplane along a spiral path. RESULTS: In upright
      subjects, the time constant of OKAN with slow phase up decreased during 1.8 g,
      whereas the horizontal OKAN showed no change in 1.8 g compared with OKAN recorded
      in 1.0 g. When the subjects were lying on their left side, the OKAN with slow
      phase right (slow phase up with respect to gravity) decreased in 1.8 g. The
      subjects tested showed larger error in setting the optokinetic stimulus in a pure
      horizontal plane in 1.8 g than in 1.0 g. The error was also larger for oblique
      stimulus in 1.8 g than in 1.0 g, but no differences were seen for the vertical
      stimulation. CONCLUSION: The changes in OKAN can be explained by an interaction
      between slow phase eye movements generated by OKAN and the Lz-nystagmus generated
      by change in the gravitational force level. The error of the perceived direction
      of the optokinetic stimulus measured during horizontal and oblique stimulation is
      also presumably due to the interaction between the visual system and the Lz
      nystagmus generated by hypergravity.

PMID- 9641404
TI  - Ethanol ingestion prolongs orthostatic intolerance in hyperthermic humans.
AB  - BACKGROUND: Both ethanol ingestion and hyperthermia contribute to orthostatic
      intolerance (OI). HYPOTHESIS: Since ethanol has been cited as a major risk factor
      for hyperthermia-related deaths, we hypothesized that ethanol exacerbates OI
      induced by hyperthermia. METHODS: There were seven subjects (four males, three
      females) rendered hyperthermic (esophageal temperature = 39 degrees C) in a 40
      degrees C water bath on two separate days: Condition 1) Control (juice
      ingestion); and Condition 2) Ethanol [ethanol (1 ml x kg(-1) body mass) and juice
      ingestion]. To test for OI, 5-min supine periods were followed by 5-min 63
      degrees head-up tilts prior to and following immersion. BPs, heart rate and
      esophageal temperatures were monitored throughout the experiments. RESULTS: For
      first and second post-immersion tilts, mean arterial BP (MAP) during tilting
      increased by 5.9 +/- 3.6 (SE) and 9.8 +/- 2.6 mm Hg in the control condition,
      while it decreased by 7.9 +/- 5.8 and 0.6 +/- 4.3 mm Hg in the ethanol condition.
      This gave significantly lower MAP (ethanol vs. control) of 63.6 +/- 3.1 vs. 71.8
      +/- 4.5 mm Hg (p < 0.05) for the first and 79.6 +/- 2.3 vs. 86.7 +/- 4.4 mm Hg (p
      < 0.05) for the second post-immersion tilts. These values were all significantly
      less (p < 0.05) than normothermic tilted values of 94.7 +/- 4.7 mm Hg in the
      ethanol and 93.6 +/- 2.9 mm Hg in the control condition. Prior to warm water
      immersion, subjects tolerated all head-up tilts. In the control condition, only
      one subject experienced orthostatic intolerance following the first post-heating
      tilt and no intolerance was experienced following 30 min post-heating. However,
      during the ethanol condition, 4 subjects experienced orthostatic intolerance
      following the first tilt with episodes of intolerance lasting as long as 80 min
      (8 supine/tilt cycles). CONCLUSION: Ethanol ingestion prolonged and increased the
      magnitude of OI in hyperthermic subjects. This may at least partly explain why
      ethanol is a major risk factor in hyperthermia-related deaths.

PMID- 9641406
TI  - Effects of hypobaric hypoxia on postural control.
AB  - BACKGROUND: While the effects of accelerative forces on the vestibular system
      have been thoroughly investigated, the effects of hypobaric conditions on the
      postural system have attracted less attention. The purpose of the study was to
      investigate if postural control is affected by hypobaric hypoxia. HYPOTHESIS:
      Moderate hypobaric hypoxia may reduce postural control. METHODS: Subjective and
      multiple objective measurements of postural control with open and closed eyes
      were made in 16 military aircrew standing on a static balance platform before,
      during, and after exposure to an altitude chamber training profile with a maximum
      altitude of 25,000 ft. RESULTS: No subjective dizziness and no clinical
      unsteadiness were noted. However, significant changes in body sway were found at
      the balance platform during hypobaric exposure at 18,000, 14,000 and 8000 ft
      compared with the baseline registrations. The relative increase in sway movements
      was greater in the eyes open condition compared with the eyes closed condition,
      and significant for movements in the anteroposterior plane but not in the lateral
      plane. Most sway parameters returned to pre-exposure values on return to ground
      level. CONCLUSIONS: Acute hypobaric hypoxia, corresponding to the tested
      altitudes, influenced postural control primarily in the anteroposterior plane
      with eyes open. This is in agreement with other studies showing that vision is
      the first of the special senses to be altered by lack of oxygen.

PMID- 9641407
TI  - Sleep and wake patterns in aircrew on a 2-day layover on westward long distance
      flights.
AB  - BACKGROUND: As part of a research program of sleep/wake disturbances in
      connection with irregular work hours and time zone transitions, the study aimed
      to describe the spontaneous sleep/wake pattern in connection with a westward
      (Stockholm to Los Angeles) transmeridian flight (-9 h) and short layover (50 h).
      HYPOTHESIS: To describe all sleep episodes and the recovery process across 4 d,
      and to relate adjustment to individual differences. METHODS: We monitored 42 SAS
      aircrew for 9 d with activity monitors and diary before, during, and after
      flight. RESULTS: During the outbound day the wake span was 21.7 h and 90% of the
      aircrew adopted local bed times on layover. The readaptation to normal sleep/wake
      patterns were rapid on the return. Napping was common (93%), especially on-board
      and before the return. Sleep efficiency dropped below 90% during layover, being
      felt to be too short and disturbed by awakenings, and gradually returned to
      normal across four recovery days. Recovery sleep was characterized by
      difficulties waking up and feelings of not being refreshed from sleep. Sleepiness
      symptoms increased during layover and gradually decreased across recovery days,
      still being elevated on day 4. CONCLUSIONS: In the present study we found that
      westward flights are associated with extended wake spans during layover,
      increased sleepiness, and slow recovery on return home. Strategic sleeping may
      counteract the effect somewhat, but individual differences are few.

PMID- 9641408
TI  - Altitude-induced migraine headache secondary to pravastatin: case report.
AB  - A 46-yr-old airline captain with many exposures to altitude chamber, fighter, and
      airliner flight developed migraine-type headaches after exposure to cabin
      altitudes above 6,000 feet. He had no prior history of chronic headaches or
      migraine. Symptoms began within days of starting pravastatin for
      hypercholesterolemia, but had not occurred during 4 yr of treatment with
      lovastatin. Headache intensity related directly to increasing pressure altitudes
      above 6,000 ft for periods of time greater than 45 min. Descent below 5,000 ft
      cabin altitudes relieved headaches. Exposure to barometric pressure changes has
      been associated with migraine headache. Vascular headaches are also a prominent
      feature of acute mountain sickness. Although the HMG-CoA reductase inhibitors are
      reported to be associated with increased occurrence of headache, the mechanism is
      poorly understood. Migraine headaches may be triggered in previously asymptomatic
      individuals by unique combinations of trigger factors. However, there have been
      no prior reports of migraine headaches triggered by the combined exposure to
      pravastatin and reduced barometric pressure.

PMID- 9641409
TI  - "First do no harm": the role of defibrillators and advanced medical care in
      commercial aviation.

PMID- 9641410
TI  - Smart Aircrew Integrated Life Support System.

PMID- 9641411
TI  - Refractive surgery: are there any limits?

PMID- 9641412
TI  - The adjustable refractive surgery concept (ARS)

PMID- 9641413
TI  - Corneal or lens refractive surgery?

PMID- 9641414
TI  - Phakic intraocular lenses. Are the sirens singing again?

PMID- 9641415
TI  - Will some see the future through phakic intraocular lenses?

PMID- 9641416
TI  - Into thin air with phakic intraocular lenses?

PMID- 9641417
TI  - Comparison of refractive corneal surgery and phakic IOLs.

PMID- 9641418
TI  - Surf's up...catch a wave with the waterjet.

PMID- 9641419
TI  - Angle-fixated anterior chamber phakic intraocular lens for myopia of -7 to -19
      diopters.
AB  - PURPOSE: To assess the safety and efficacy of a second generation, anterior
      chamber phakic intraocular lens (Baikoff Model ZB5M) in patients with high
      myopia. METHODS: One hundred and twenty-one patients (134 eyes) with myopia of 
      7.00 to -18.80 D were implanted with the ZB5M lens and followed for 18 to 52
      months; the number of eyes evaluated was: 6 months (104 eyes), 1 year (91 eyes),
      18 months (78 eyes), 2 years (68 eyes), and 3 years (35 eyes). RESULTS:
      Postoperative spherical equivalent refraction averaged -1.00 D and the error in
      refractive correction (achieved minus intended) averaged -0.40 D during the first
      2 years, increasing -to -1.30 D refraction and -0.60 D error in refractive
      correction at 3 years. At 2 years, approximately 40% of eyes had a spherical
      equivalent refraction within +/-0.50 D, and 65% within +/-1.00 D. The uncorrected
      distance visual acuity was 0.048 at baseline and 0.5 at 3 years; near visual
      acuity was 0.21 at baseline and approximately 0.7 over the 3 years of follow-up.
      Spectacle-corrected distance visual acuity at baseline was 0.54; it improved to
      0.7. Near visual acuity was 0.65 at baseline and it improved to approximately
      0.75. Endothelial cell counts in the central and peripheral cornea were reduced
      by an average 3.3% at 6 months, declining an additional 1% to 2% over the
      remaining follow-up period. Regression analyses indicated that most of the
      endothelial cell loss was due to surgery. Additional complications included
      halos/glare in 37 of 133 eyes (27.8%) and iris retraction with pupillary
      ovalization in 30 of 133 eyes (22.6%). The intraocular lens was exchanged in four
      of 133 eyes (3.0%) and removed in three of 133 eyes (2.3%), the latter because of
      halos (one eye) and a flat anterior chamber with severe inflammation (two eyes).
      CONCLUSIONS: Implantation of the Baikoff ZB5M lens in the anterior chamber of
      phakic eyes significantly reduced high myopia and produced a stable refractive
      outcome over the 3 years, accompanied by marked improvement in uncorrected
      distance visual acuity and minimal, non-progressive damage to the corneal
      endothelium. Frequent complications included pupillary ovalization and
      halos/glare. Improvements in accuracy of IOL power calculations are needed.

PMID- 9641420
TI  - Posterior chamber phakic intraocular lens for myopia of -8 to -19 diopters.
AB  - PURPOSE: To examine the efficacy, predictability, stability, and safety of
      posterior chamber phakic intraocular lens (IOL) implantation in patients with
      extreme myopia. METHODS: We analyzed the results of 124 eyes that received a
      posterior chamber hydrogel collagen plate phakic IOL (Staar Collamer Implantable
      Contact Lens, ICL) for the correction of their myopia. The target postoperative
      spherical equivalent refraction was emmetropia. Mean follow-up was 11 months
      (range 1 to 36 mo). RESULTS: The mean preoperative spherical equivalent
      refraction was -13.38 +/- 2.23 D (range, -8.50 to -18.63 D). Mean postoperative
      spherical equivalent refraction at last examination was -0.78 +/- 0.87 D (range,
      +1.63 to -3.50 D), with 69% (86 eyes) within +/-1.00 D and 44% (55 eyes) within
      +/-0.50 D of emmetropia. The refraction remained stable with a statistically
      insignificant change (p > 0.05 at each interval) during follow-up. A gain of two
      or more lines of spectacle-corrected visual acuity was seen in 36% (45 eyes) at
      last examination. One eye (0.8%) lost two or more lines of spectacle-corrected
      visual acuity from a retinal detachment. CONCLUSION: Posterior chamber phakic IOL
      implantation with the Staar Collamer plate lens is an effective and safe method
      for reducing or correcting myopia between -8 and -19 D. Gains in spectacle
      corrected visual acuity were common, and results suggested good refractive
      stability. Improvements in phakic IOL power calculation formulas are needed to
      improve the predictability of refractive outcome.

PMID- 9641421
TI  - Posterior chamber phakic intraocular lens for hyperopia of +4 to +11 diopters.
AB  - PURPOSE: To examine the efficacy, predictability, stability, and safety of
      posterior chamber phakic intraocular lens (IOL) implantation in eyes with high
      hyperopia. METHODS: We analyzed the results of 24 eyes that received a posterior
      chamber hydrogel-collagen plate phakic IOL (Staar Collamer Implantable Contact
      Lens, ICL) for the correction of hyperopia with the goal of emmetropia. Mean
      follow-up was 8.4 months (range, 1 to 18 mo). RESULTS: The mean preoperative
      spherical equivalent refraction was +6.51 +/- 2.08 D (range, +3.75 to +10.50 D).
      Mean postoperative spherical equivalent refraction at last examination was -0.39
      +/- 1.29 D (range, +1.25 to -3.88 D), with 79% (19 eyes) within +/-1.00 D and 58%
      (14 eyes) within +/-0.50 D of emmetropia. Postoperative uncorrected visual acuity
      at last examination was 20/20 or better in 8% (two eyes) and 20/40 or better in
      63% (15 eyes). A gain of two or more lines of spectacle-corrected visual acuity
      was seen in two eyes (8%) at last examination. One eye (4%) lost two or more
      lines of spectacle-corrected visual acuity due to progressive neovascular
      glaucoma initiated by early postoperative pupillary block. CONCLUSION: Posterior
      chamber phakic IOL implantation with the Staar Collamer plate lens is an
      effective method for correcting high hyperopia. Large, patent iridotomies are
      important in hyperopic eyes to lower the risk of postoperative pupillary block.
      Improved phakic IOL power calculation formulas will refine predictability of
      refractive outcome.

PMID- 9641422
TI  - Iatrogenic keratectasia after laser in situ keratomileusis.
AB  - BACKGROUND: Lamellar refractive surgery reduces the biomechanical strength of the
      cornea which may lead to mechanical instability and keratectasia. METHODS: Three
      eyes had laser in situ keratomileusis (LASIK) for myopia from -10.00 to -13.50 D.
      The procedures were performed with two different wide-field excimer lasers and
      two different microkeratomes. The patients were followed up to 1 year after
      surgery. RESULTS: Central steep areas developed between 1 and 8 months after
      surgery. In contrast to conventional central steep islands, these showed rapid
      progression and were interpreted as keratectasia. CONCLUSION: Iatrogenic
      keratectasia represents a complication after LASIK that may limit the range of
      myopia correction. Based on biomechanical considerations we recommend a residual
      corneal thickness of the stromal bed of at least 250 microm.

PMID- 9641423
TI  - Five and three year follow-up of photorefractive keratectomy for myopia of -1 to 
      6 diopters.
AB  - BACKGROUND: To report the 5 and 3 year results of photorefractive keratectomy for
      -1 to -6 D of myopia and less than 1.50 D astigmatism. METHODS: All eyes were
      treated with a VISX 20/20 excimer laser with an ablation diameter of 5 mm. Our
      initial series of 133 eyes were treated in four groups: IIA, IIB, III and III No
      Nitrogen and reported on previously with follow-up from 6 to 36 months. The
      present report extends the observation period to 3 and 5 years for 114 eyes.
      RESULTS: Groups IIA and IIB were followed for 5 years and Groups III and III No
      Nitrogen for 3 years. Group IIA achieved 77% (10 of 13 eyes) +/-1.00 D (54%
      within +/-0.50 D) of emmetropia with stability from 6 months and 54% (seven of 13
      eyes) had visual acuity of 20/20 or better. In Group IIB, 35% (six of 17 eyes)
      were +/-1.00 D (18% within +/-0.50 D) of emmetropia and stable from 18 months.
      Two of 17 eyes (12%) had 20/20 or better visual acuity. Group III had 76% (42 of
      55 eyes) within +/-1.00 D (51% within +/-0.50 D) of emmetropia with stability
      after 12 months; 60% (33 of 55 eyes) had 20/20 or better visual acuity. Group III
      No Nitrogen had 73% (11 of 15 eyes) within +/-1.00 D (60% within +/-0.50 D) of
      emmetropia and were stable after 6 months; 47% (seven of 15 eyes) had 20/20 or
      better visual acuity. There was no hyperopic refractive shift. No correlation was
      found between the percent of correction achieved and preoperative amount of
      myopia, age, or sex. CONCLUSION: Refractive stability was achieved from 6 to 12
      months in most eyes; a few required 18 months to stabilize. Groups IIA and III
      continued to be stable; Groups HB and III No Nitrogen showed mild regression that
      was not statistically significant.

PMID- 9641424
TI  - Unilateral refractive keratotomy for anisometropia.
AB  - BACKGROUND: In anisometropia, the asymmetry of refractive error produces
      disparity of image magnification (aniseikonia) that can create visual discomfort,
      especially when asymmetry is 3.00 diopters or more. METHODS: A prospective study
      of 20 eyes of 20 patients between 18 and 61 years of age who underwent unilateral
      radial and/or transverse keratotomy was conducted; results of at least 12 months
      follow-up are presented. The efficacy of keratotomy was evaluated by the
      following criteria: 1) change in spherical and cylindrical refraction, 2)
      decrease in refraction difference between two eyes of each patient, 3) change in
      spectacle-corrected visual acuity, and 4) change in binocular vision functions
      and asthenopic complaints. RESULTS: Mean decrease in spherical refractive error
      was 3.66 +/- 1.58 D (range, 1.25 to 7.50 D) and 2.08 +/- 0.81 D (range, 1.00 to
      3.50 D) in astigmatic refraction. The mean refraction difference between two eyes
      was 4.90 +/- 2.20 D preoperatively, and this difference regressed to 1.79 +/-
      1.42 D postoperatively. Spectacle-corrected visual acuity increased in seven eyes
      (35%), remained the same in 12 eyes (60%) and decreased in one eye (5%). All
      patients reported relief of asthenopic complaints. Fusion amplitudes increased in
      12 (60%) patients. Stereoscopic vision improved in five (25%) patients.
      CONCLUSION: Monocular refractive keratotomy can significantly decrease
      anisometropia.

PMID- 9641425
TI  - Measurement of radial keratotomy clear zone diameters.
AB  - BACKGROUND: To compare the accuracy of photographic measurements to slit-lamp
      measurements of radial keratotomy clear zone diameters in order to develop an
      independent, objective, unbiased, and reproducible method of verifying clinical
      observations. METHODS: Twenty-five patients (48 eyes) following radial keratotomy
      had matched slit-lamp and photographic measurements of the diameter of the
      central clear cornea between the ends of opposite radial incision pairs. Matched
      slit-beam, photographic, and pathologic observations were compared statistically.
      RESULTS: Two hundred fifty-four slit-lamp clear zone diameter measurements were
      obtained. In twenty instances (8%), the radial incision end-point could not be
      identified on the photograph. For the remaining 234 measurements, the mean slit
      lamp clear zone diameter was statistically smaller than the photographic
      measurement by 0.03 mm (t-test, p = 2.2 x 10(-5)). The slit-lamp and photographic
      clear zone measurements were strongly positively correlated (Pearson r = 0.99, p
      < 1.0 x 10(-15)). Matched slit-lamp, photographic, and pathologic clear zone
      measurements (N=8) in one excised corneal button were not statistically
      different. CONCLUSIONS: For radial keratotomy clear zone diameters, slit-beam
      measurements and photographic caliper measurements yield indistinguishable
      results that are highly concordant over a wide range of diameters. Both slit-beam
      and photographic measurements yield accurate and reliable results that reflect
      the true pathologic achieved clear zone diameter following radial keratotomy
      surgery.

PMID- 9641426
TI  - Principles and microscopic confirmation of surface quality of two new waterjet
      based microkeratomes.
AB  - PURPOSE: The HydroBlade and the HydroBrush keratomes are waterjet-based devices
      for corneal surgery that operate at normal intraocular pressure in two different
      modes: removal of parallel or shaped lenticules or hinged flaps with a small
      diameter, high speed waterjet; and removal of the epithelium with a waterjet
      sheet. The operating principles as well as histology of the cut surfaces are
      described. METHODS: A flap was made in one cadaver eye with a Chiron ACS keratome
      and in the second eye with the HydroBlade keratome. The epithelium was removed in
      one cadaver eye with a surgical blade and in the second eye by the HydroBrush
      keratome. Scanning and transmission electron microscopy and light microscopy was
      obtained. RESULTS: The HydroBlade keratome cleaved only cross-linking fibrils and
      left intact keratocytes. Shape and dimensions of the flap were accurate. There
      was no observable hydration or significant heating of the tissue. Mechanical
      forces on the cornea were small. The HydroBrush keratome removed the epithelium
      quickly, left no epithelial debris, and did not damage Bowman's layer.
      CONCLUSION: With the HydroBlade keratome, the cuts are ideal blunt dissections.
      Epithelial removal with the HydroBrush keratome is effective and quick.

PMID- 9641427
TI  - Hydroepithelial keratectomy in rabbits with a waterjet-based instrument.
AB  - BACKGROUND: Corneal epithelial removal finds multiple applications in ophthalmic
      surgery (epithelial herpes infections, recurrent epithelial erosion, corneal
      ulcers and plaques, and intraoperative epithelial clouding). Photorefractive
      keratectomy is initiated by removal of the epithelium. Current techniques for
      epithelial removal are suboptimal. We studied the safety and effectiveness of a
      new technique, hydroepithelial keratectomy, performed with the HydroBrush
      keratome on live rabbits. METHODS: Eighteen rabbits (18 eyes) underwent
      hydroepithelial keratectomy and 18 rabbits (18 eyes) underwent epithelial removal
      with a surgical blade (blade group). Twelve rabbits were euthanized immediately
      after the procedure. Twenty-four rabbits were followed for up to 120 hours after
      treatment. Ultrastructural analysis was performed with light and electron
      microscopy. RESULTS: The hydroepithelial keratectomy group healed a mean 53 hours
      after treatment; the blade group healed a mean 78 hours after treatment. The
      HydroBrush keratome exposed the basement membrane and the basal cell membrane of
      the epithelium. The blade exposed patches of basement membrane, as well as stroma
      and cell debris. CONCLUSIONS: Hydroepithelial keratectomy with the HydroBrush
      keratome is effective and safe. Wound healing after hydroepithelial keratectomy
      is faster than after blade removal. Unlike the blade, the HydroBrush keratome
      exposed a smooth surface, devoid of debris, with well-defined edges and round
      shape without hydration nor dehydration of the tissue.

PMID- 9641428
TI  - Mycobacterium chelonae keratitis following laser in situ keratomileusis.
AB  - Corneal infection after laser in situ keratomileusis (LASIK) is rare. However,
      surgical trauma or breakdown of epithelium increases the risk of surface
      infection. We present the case of a 45 year old woman who developed keratitis due
      to Mycobacterium chelonae 1 month after LASIK with the Mini-Laser Sight 2000
      excimer laser. After an initial improvement following antibiotic therapy the
      infection progressed until it was necessary to perform penetrating keratoplasty,
      with a successful result.

PMID- 9641429
TI  - Contrast sensitivity and glare disability after radial keratotomy and
      photorefractive keratectomy.

PMID- 9641430
TI  - The prediction of surgically induced refractive change from corneal topography.

PMID- 9641431
TI  - Allergic conjunctivitis as a risk factor for regression and haze after
      photorefractive keratectomy.

PMID- 9641432
TI  - Patellar tendon ultrasonography in asymptomatic active athletes reveals
      hypoechoic regions: a study of 320 tendons. Victorian Institute of Sport Tendon
      Study Group.
AB  - OBJECTIVE: To compare patellar tendon sonographic findings in active, currently
      asymptomatic, elite athletes with those in nonathletic controls. DESIGN: Cross
      sectional cohort study with convenience control sample. SETTING: The Victorian
      Institute of Sport Tendon Study Group, an institutional elite athlete study group
      in Australia. PATIENTS AND PARTICIPANTS: Two hundred elite male and female
      athletes from the sports of basketball, cricket, netball, and Australian rules
      football. Forty athletes who had current symptoms of jumper's knee were excluded
      from analysis, leaving 320 subject tendons in athletes who were currently
      asymptomatic. Twenty-seven nonathletic individuals served as controls. MAIN
      OUTCOME MEASURE: Sonographic patellar tendon appearance. We measured the
      dimensions of subject tendons and noted the presence or absence of hypoechoic
      regions and tendon calcification. Dimensions of hypoechoic regions were measured,
      and approximate cross-sectional areas were calculated. Chi-squared analysis was
      used to test the prevalence of hypoechoic regions in subjects and controls and
      men and women. RESULTS: In currently asymptomatic subjects, hypoechoic regions
      were more prevalent in athlete tendons (22%) than in controls (4%), in male
      subject tendons (30%) than in female subjects (14%), and in basketball players
      (32%) than in other athletes (9%) (all p < 0.01). Bilateral tendon abnormalities
      were equally prevalent in men and women but more prevalent in basketball players
      (15%) than in other athletes (3%) (p < 0.05). Sonographic hypoechoic regions were
      present in 35 of 250 (14%) patellar tendons in athletes who had never had
      anterior knee pain. CONCLUSIONS: Patellar tendon sonographic hypoechoic areas
      were present in asymptomatic patellar tendons of a proportion of elite athletes
      but rarely present in controls. This has implications for clinicians managing
      athletes with anterior knee pain.

PMID- 9641433
TI  - The effectiveness of topical diclofenac for lateral epicondylitis.
AB  - INTRODUCTION: Gastrointestinal upset and local pain commonly limit the use of
      oral nonsteroidal anti-inflammatory drugs and corticosteroid injection as
      treatments for lateral epicondylitis. Transdermal administration of an anti
      inflammatory drug could avoid these adverse effects. PURPOSE: To determine the
      effectiveness of topical diclofenac as a treatment of lateral epicondylitis.
      METHODS: A convenience sample of 14 subjects meeting clinical criteria of chronic
      lateral epicondylitis participated in this randomized, double blind, crossover
      study. Each subject applied a pluronic lecithin liposomal organo-gel (PLO) over
      the affected lateral elbow three times daily for I week, followed by a 1-week
      "washout" period of no gel. A second topical PLO gel was then applied similarly
      for 1 week. Both gels were identical, but only one gel contained 2% diclofenac.
      Treatment order was randomized, and both the subject and tester were blinded.
      Pain and isometric wrist extension strength were measured using a visual analog
      pain scale (VAS) and a mounted manual muscle testing dynamometer, respectively,
      at the following time periods: just before application of the first gel, the last
      day of using the first gel, the last day of the washout week, and the last day of
      using the second gel. Analysis was performed using repeated measures analysis of
      variance. RESULTS: When subjects used diclofenac PLO, pain was significantly less
      than that during the pretreatment, washout, and placebo PLO periods (mean VAS:
      diclofenac PLO, 2.1; pretreatment, 3.5; washout, 3.4; placebo PLO, 3.6). Average
      wrist extension strength was significantly greater when subjects used diclofenac
      PLO (8.4 kg) than it was before treatment (5.9 kg). One subject developed a local
      rash while using diclofenac PLO. CONCLUSION: Topical 2% diclofenac in PLO appears
      to provide effective short-term reduction in elbow pain and wrist extensor
      weakness associated with chronic lateral epicondylitis.

PMID- 9641434
TI  - A randomized controlled trial of the effect of naproxen on delayed onset muscle
      soreness and muscle strength.
AB  - OBJECTIVE: To determine the effect of naproxen in attenuating the symptoms
      (muscle soreness level) and signs (plasma creatine kinase [CK] activity and
      muscular strength decrement) of delayed onset muscle soreness (DOMS) induced by
      repeated bouts of eccentric exercise. DESIGN: The design was a randomized, double
      blind, placebo-controlled, crossover trial with two testing phases of 8 days'
      duration that were separated by a "washout" period of 7 days. SETTING: University
      based sports science center. PARTICIPANTS: Twenty healthy male volunteers who
      responded to a notice in the university's athletic complex. INTERVENTIONS:
      Eccentric single-leg exercises were performed on days 1, 3, and 4 to induce DOMS
      in the quadriceps muscles. Naproxen or placebo tablets (500 mg) were taken orally
      twice per day beginning on day 2 and continuing until the end of the testing
      phase. MAIN OUTCOME MEASURES: Perception of muscle soreness and knee extensor
      torque were evaluated daily throughout each phase. Plasma CK levels were
      evaluated on days 1, 3, 6, and 8 of each phase. RESULTS: After the eccentric
      exercise, plasma CK levels were similarly elevated in both naproxen and placebo
      conditions (F=1.42; p=0.25). After DOMS developed, naproxen reduced the
      perception of soreness on day 3, when muscle soreness was highest (F=2.20;
      p=0.04). After treatments with naproxen, peak quadriceps torque during leg
      extension at 60 degrees/s was higher than that after treatment with the placebo
      (F=4.77; p=0.04). There were no significant differences between the naproxen and
      placebo conditions for leg extension at 180 degrees/s (F= 1.66; p=0.21) and 300
      degrees/s (F=0.71; p=0.41). CONCLUSION: The data indicate that therapeutic doses
      of naproxen do not prevent CK release into the plasma but decrease the perception
      of muscle soreness and positively influence quadriceps peak torque.

PMID- 9641435
TI  - Comparison of injuries in classic and skating Nordic ski techniques.
AB  - OBJECTIVE: To compare types and anatomic distribution of injuries between cross
      country skiers using the classic and skating ski techniques. DESIGN: Descriptive
      self-administered survey. SUBJECTS: Midlevel competitors in the 1996 American
      Birkebeiner cross-country ski marathon (55 km). DESCRIPTION OF SURVEY: A self
      administered 21-item questionnaire regarding skiing-related injuries occurring
      during training before the race or during the marathon. The respondent was asked
      for information regarding any skiing-related injury or complaint that occurred
      during training or while participating in the American Birkebeiner ski race. This
      tool also collected information regarding training habits, equipment selection,
      and skier demographics. Responses were coded on a Mark-Sense form and compiled by
      a computerized code reader. MAIN RESULTS: A total of 833 surveys were returned
      for an overall response rate of 55%. The overall self-reported injury rate for
      the surveyed group was 234 per 1000 skiers (i.e., 23.4% of skiers sustained an
      injury during the race). Most of these injuries were minor; only 4.6% of all
      skiers reported lost training time because of a race injury, and only 2.8% of all
      skiers sought treatment from a health care provider for a race-related injury.
      There was no statistically significant difference between the two techniques
      either in overall injury rate (p=0.33) or in the location of the injury
      (p=0.158). The injury rates were 23% and 27%, respectively, for skating and
      classical techniques. The incidence of more serious injuries (those requiring
      medical attention) was 2.7% for skaters and 3.1% for classical skiers. No
      statistically significant relation was found between pole length and the
      development of injuries. In addition, the likelihood of sustaining an injury was
      independent of age and training distance. CONCLUSIONS: The overall injury rates
      in this study were much higher than those previously reported in the literature,
      but no significant difference in injuries between the two skiing techniques was
      found. The incidence of more severe injuries, defined as those requiring medical
      treatment, was consistent with previous reports. Prior assumptions regarding
      equipment relationships to injuries were not substantiated by the findings. In
      spite of significant changes in the equipment and technique designed to enhance
      speed, cross-country skiing remains a safe sport, with its participants
      relatively free of serious injuries. Further investigation is required to
      determine whether other aspects of the sport, such as pole grip design, ski
      construction, and skier skill level, have any relation to injury patterns.

PMID- 9641436
TI  - Cervical spine alignment in immobilized hockey players: radiographic analysis
      with and without helmets and shoulder pads.
AB  - OBJECTIVE: To establish the appropriate technique for cervical immobilization of
      the hockey player with an acute neck injury, we analyzed the alignment of the
      cervical spine in healthy volunteers with combinations of applied hockey
      equipment and assessed the amount of cervical spine motion possible in a secured
      hockey helmet. Our hypothesis was that there is a significant difference among
      various positions of the cervical spine with and without equipment and with
      active motion in a secured helmet. DESIGN: We analyzed lateral cervical spine
      radiographs of eight healthy male volunteers immobilized on a backboard with the
      following combinations of hockey equipment: shoulder pads and helmet, shoulder
      pads only, helmet only, no equipment, and neck flexion and extension with helmet
      and shoulder pads on and helmet secured to the backboard. SETTING: Large
      university hospital, tertiary care center. RESULTS: Cervical lordosis without
      equipment (control) was not significantly different than cervical lordosis with
      shoulder pads and helmet applied (p=0.31). Subjects with shoulder pads averaged
      8.9 degrees more lordosis than did controls (p= 0.0002) and 6.6 degrees more
      lordosis than did subjects with shoulder pads and helmets (p=0.027). Subjects
      with shoulder pads and a helmet secured to the backboard were able to flex and
      extend the cervical spine 12.9 degrees compared with the control position (p
      =0.009). CONCLUSIONS: In an acute cervical spine injury involving an ice hockey
      player, we recommend immobilization in both the helmet and the shoulder pads,
      with removal of both pieces of equipment in a controlled hospital setting and
      only after initial radiographic examination. We also recommend securing the
      player's chin to prevent as much head and neck motion as possible during
      transport and transfers.

PMID- 9641437
TI  - The effects of muscular fatigue on shoulder proprioception.
AB  - OBJECTIVE: To assess the influence of muscular fatigue on active and passive
      shoulder proprioception within the midrange of rotation. DESIGN: A randomized
      controlled, before-and-after design. SETTING: Neuromuscular research laboratory.
      PARTICIPANTS: Twenty recreationally active men (mean age, 23.81+/-2.77 years)
      were randomly assigned to either a control or a fatigue group. Exclusion criteria
      were any history of upper extremity injury or pathology, cardiovascular disease,
      or disease affecting the sensory system. INTERVENTION: Shoulder proprioception
      was assessed by active reproduction of passive positioning (ARPP), active
      reproduction of active positioning (ARAP), reproduction of passive positioning
      (RPP), and threshold to detect passive motion (TTDPM). For each test direction,
      the experimental group performed two bouts of maximal reciprocal concentric
      isokinetic internal and external contractions at 180 degrees/s until peak torque
      decreased to 50% of the established maximum voluntary contraction. After two
      bouts of the fatigue protocol, subjects were randomly assessed for proprioception
      into internal or external rotation. MAIN OUTCOME MEASURES: The absolute angular
      error for active and passive proprioception was measured on the Biodex System II
      Isokinetic Dynamometer (Biodex Medical Inc., Shirley, NY, U.S.A.) and a
      proprioception testing device, respectively. MAIN RESULTS: A two-factor repeated
      measures analysis of variance revealed no significant interactions between the
      experimental and control groups for ARPP, ARAP, RPP, or TTDPM. CONCLUSIONS:
      Shoulder proprioception was not affected by the short-duration, high-intensity
      protocol used in this study. This may be due to the lack of an extended recovery
      period observed with this type of fatigue regimen.

PMID- 9641438
TI  - The fate of meniscal tears after anterior cruciate ligament reconstruction.
AB  - OBJECTIVE: To investigate the incidence of meniscal pathology and subsequent
      treatment at an index arthroscopically assisted reconstruction of acute ACL tears
      (<3 weeks after injury) and to determine the outcome of meniscal pathology.
      DESIGN: Cohort study with average postoperative follow-up of 40 months (range, 24
      76 months). SETTING: University-based sports medicine center. PATIENTS: Series of
      162 patients admitted between January 1989 and July 1993. Follow-up was obtained
      for 105 patients. MAIN OUTCOME MEASURES: Initial presence, location, and
      treatment of meniscal tears. Subsequent surgery performed and further
      investigation or surgery being planned. RESULTS: Approximately 40% of patients
      had meniscal pathology at the index procedure. Most tears were in the lateral
      meniscus (34 of 45). All posterolateral tears and most other small tears were
      left untreated (25 of 45). Partial meniscectomies were performed on 17 large,
      complex, or radial tears that were not amenable to meniscal resuturing. Three
      meniscal repairs were performed on large, unstable tears. Most patients achieved
      good functional results. Of the five patients who required late meniscal surgery,
      three had normal menisci at the index procedure. The other two were asymptomatic
      until experiencing a reinjury. Despite ACL reconstruction in the acute phase,
      only two patients required treatment for postoperative arthrofibrosis. Three
      patients required revision ACL reconstruction after return to full activities and
      experiencing reinjuries. CONCLUSIONS: Stable tears of both lateral and medial
      menisci remain asymptomatic at 2 to 6 years' follow-up if treated conservatively.
      Those requiring further surgery had de novo tears or tears that were asymptomatic
      before reinjury. Although repair may be of benefit for large flap or bucket
      handle tears, it does not appear necessary for most tears and may increase the
      incidence of postoperative stiffness.

PMID- 9641439
TI  - Repetitive activity alters perfusion of proximal interphalangeal joints of the
      human hand.
AB  - OBJECTIVE: To examine whether competitive volleyball players show any difference
      in perfusion of their proximal interphalangeal (PIP) joints compared with a
      healthy group of subjects. Also to assess the viability of a dual wavelength
      laser Doppler imager (LDI) in making these measurements. SETTING: Physiology
      laboratory. PARTICIPANTS: Ten active volleyball players who had experienced
      repetitive finger joint injury and 12 age- and sex-matched normal control
      subjects. MAIN OUTCOME MEASURES: Using a modified LDI incorporating a near-
      infrared (850 nm) laser as well as a standard red (633 nm) laser, scans were
      performed over the dorsum of the hands of the volleyball players and the control
      group. RESULTS: Higher perfusion values were obtained with the 850-nm laser than
      with the red 633-nm laser. When referenced to adjacent skin blood flow, perfusion
      over PIP joints of volleyball players was found to be significantly higher than
      that in control subjects (p=0.00012; n=10-12). CONCLUSIONS: The higher perfusion
      values obtained using the 850-nm laser suggest that the longer wavelength laser
      is measuring perfusion in a greater volume of tissue, which could include
      subcutaneous structures. Volleyball players have significantly higher perfusion
      over the PIP joints, which is unlikely to be due to differences in skin perfusion
      over the two regions but is more likely to be related to hyperemia of the
      underlying PIP joints. The reason for increased PIP perfusion is not clear; it
      may represent ongoing tissue inflammation due to repeated injury, or it could be
      an adaptive response to the stresses placed on these joints by this type of
      repetitive activity. CLINICAL RELEVANCE: Near-infrared laser Doppler imaging has
      the potential to provide a noninvasive clinical assessment of finger joint
      injuries.

PMID- 9641440
TI  - In-line skating: use of protective equipment, falling patterns, and injuries.
AB  - OBJECTIVE: To determine the use of protective equipment, reasons for nonuse of
      protective equipment, and patterns of injury, falls, and stopping techniques of
      recreational in-line skaters. DESIGN: Survey. PARTICIPANTS: 313 in-line
      recreational skaters observed skating in the parks, on bicycle trails, and on
      parkways in Milwaukee, Wisconsin and Columbus, Ohio were asked to participate in
      a short survey in 1995. MAIN OUTCOME MEASUREMENTS: The frequency of in-line
      skater use of protective equipment, reasons for nonuse, patterns of injury, and
      patterns of falls. RESULTS: Protective equipment was worn most of the time in the
      following proportions of skaters [95% confidence interval in brackets]: wrist
      guards (51%) [44.7%-58.1%]; knee pads (36%) [29.3%-42.5%]; elbow pads (15%) [8.4%
      22.8%]; and helmets (15%) [8.0%-22.0%]. Reasons cited for not using protective
      equipment included lack of perceived need (47.3%), discomfort (37.5%), cost
      (15.9%), and undesirable appearance (15.2%). Stopping techniques included skating
      off into the grass (14.6%) [11.8%-17.4%] and voluntarily falling (3.5%) [2.1%
      4.9%]. Causes of involuntary falls included spontaneous loss of balance (32.9%)
      [28.9%-36.9%], hitting rocks or other small objects (17.3%) [14.4%-20.2%], uneven
      pavement (17%) [14.2%-19.8%], and failure to stop (11.3%) [8.4%-14.2%]. Site of
      initial impact after falling included the hands and wrists (44.6%) [38.3%-50.9%],
      the knees (19.6%) [16.4%-22.8%], and the buttocks region (17.2%) [14.3%-20.1%].
      Injuries had occurred in 26% of the skaters; 14% of injuries were fractures.
      CONCLUSIONS: In-line skaters often do not wear protective equipment because they
      believe it is not necessary. Recent studies have suggested, however, that
      protective equipment does prevent injuries. Physicians should counsel their
      patients who are in-line skaters to use protective equipment.

PMID- 9641441
TI  - Body fatness and increased injury rates in high school football linemen.
AB  - OBJECTIVE: To determine whether associations exist between body fatness and
      injury rates in high school football linemen. DESIGN: Prospective, injury
      surveillance study during a 2-week preseason and 10-week regular season. SETTING:
      10 public high schools in Texas. PARTICIPANTS: Two hundred fifteen varsity and
      junior varsity high school football linemen. MAIN OUTCOME MEASURES: Injury rates
      (injuries per 1000 hours of playing time) for groups of players above a given
      body fat level and at or below a given body fat level. Rates were computed as the
      number of injuries per group divided by the group's aggregate playing time
      (practice + game time). The null hypothesis was that there is no difference in
      injury rates between players above a given level of body fat and those at or
      below that level of body fat. Body fat was determined from chest, abdomen, and
      thigh skinfold measurements using standard conversion equations. Body mass index
      (BMI) (kg/m2) was also calculated for each player. RESULTS: The overall injury
      rate was 5.66 injuries per 1000 hours of playing time. Percent body fat ranged
      from 9.3% to 40.2%. BMI ranged from 19.9 to 46.6 kg/m2. Sixty-seven players
      sustained 86 injuries, the most common of which were ankle sprains and medial
      collateral ligament sprains. No difference in overall injury rates between higher
      and lower fat groups was seen at any body fat level. Players in higher body fat
      groups, however, had significantly greater lower extremity injury rates than did
      players in lower fat groups between 18% and 27% body fat and again 32% to 33%,
      but not at intermediate levels or >33%. Players in higher BMI groups had
      significantly greater lower extremity injury rates than did players in lower BMI
      groups throughout the range from 24 to 36 kg/m2, except at 34 kg/m2. CONCLUSION:
      Both higher body fatness and BMI were associated with increased rates of lower
      extremity injury among high school football linemen. BMI appears to be associated
      more consistently with increased lower extremity injury rates than is body fat.

PMID- 9641442
TI  - A clinical test for superior glenoid labral or 'SLAP' lesions.
AB  - OBJECTIVE: To describe a clinical test associated with unstable lesions of the
      superior glenoid labrum-long head biceps tendon origin, or SLAP (superior labrum
      anterior to posterior). DESIGN: Description of a newly discovered clinical sign
      that correlated with SLAP pathology. Retrospective review of 66 consecutive
      arthroscopically confirmed SLAP lesions to determine the sensitivity of the
      SLAPprehension test. SETTING: Orthopedic sports medicine clinics with an emphasis
      on shoulder problems. PATIENTS: Patients with shoulder pain and arthroscopically
      verified lesions of the superior glenoid labrum and conjoined long head biceps
      tendon. INTERVENTION: Shoulder arthroscopy and in some cases arthroscopic SLAP
      lesion repair. OUTCOME MEASURES: Nonapplicable. RESULTS: The SLAPprehension test
      involves cross chest adduction (horizontal flexion) of the affected shoulder with
      the elbow extended and forearm pronated. A positive maneuver produces either
      apprehension, pain referable to the bicipital groove, and an audible or palpable
      click. The test is repeated with the forearm supinated, which must cause
      diminution of the pain. Mechanically, elbow extension and forearm pronation
      places traction on the long head biceps tendon. When anterior scapular
      protraction is limited by the clavicle, further adduction entraps the unstable
      biceps tendon and superior glenoid labrum between the glenoid fossa and humeral
      head. Forearm supination decreases traction on the long head biceps tendon and
      allows for reduction of the unstable labrum complex with lessening of the pain. A
      retrospective chart review of 66 consecutive arthroscopically verified shoulders
      with SLAP lesions revealed the SLAPprehension test to be 87.5% sensitive for
      unstable SLAP lesions. CONCLUSIONS: The SLAPprehension test is helpful in the
      clinical evaluation of patients with unstable superior glenoid labrum lesions
      whose symptoms are often confused and overlap with those of shoulder impingement
      or acromioclavicular arthrosis.

PMID- 9641443
TI  - On-field management of potential cervical spine injury in helmeted football
      players: leave the helmet on!
AB  - OBJECTIVE: Improper handling of an unstable neck injury in the prehospital
      setting may result in potential iatrogenically induced neurologic injury. On-site
      management of the neck-injured, helmeted football player differs from that of
      other traumatic cervical spine injuries. Controversy still exists regarding
      helmet removal protocols for stabilizing the cervical spine of helmeted football
      players with a suspected neck injury. This article provides a critical review of
      the scientific evidence on cervical spine management in helmeted football players
      with a suspected cervical spine injury. DATA SOURCES: A computerized literature
      search of databases (MEDLINE, Sportdiscus) and a manual search of journals from
      the sports medicine, emergency medicine, orthopedic, and athletic training
      literature identified articles related to the topic. Additional references were
      reviewed from the bibliographies of the retrieved articles. STUDY SELECTION:
      Conclusions are based on five quasi-experimental study designs evaluating
      motorcycle, football, and hockey helmet removal. In addition, an attempt was made
      to correlate articles relating to airway and cervical spine management in general
      trauma to the helmeted athlete. MAIN RESULTS: Several studies support the
      recommendation not to remove the helmet or shoulder pads in the prehospital
      setting unless absolutely necessary. If necessary, both helmet and shoulder pads
      should be removed together as a unit. There are neither published studies in
      support of helmet removal nor any case reports of increased morbidity to athletes
      because of failure to remove the helmet in the prehospital setting. CONCLUSIONS:
      Although studies support the notion that iatrogenic neurologic deterioration may
      occur with improper handling and attempted removal of the helmet in the
      prehospital setting, there is no literature to support increased morbidity
      associated with not removing helmet and shoulder pads. Stabilization of the
      cervical spine in an injured football player does not require routine prehospital
      removal of the helmet and shoulder pads before transport.

PMID- 9641444
TI  - The traveling athlete: issues relating to the Commonwealth Games, Malaysia, 1998.

PMID- 9641445
TI  - Osteonecrosis of the tarsal navicular in two adolescent soccer players.

PMID- 9641446
TI  - Arthroscopic findings in luxatio erecta of the glenohumeral joint: case report
      and review of the literature.
AB  - PURPOSE: We report the case of an inferior glenohumeral dislocation of the
      shoulder in which arthroscopic assessment showed an extensive detachment of the
      labral-biceps tendon complex (Bankart and superior labrum anterior posterior
      [SLAP] lesions). We sought to review the literature to compare our findings with
      the reported lesions in this type of shoulder dislocation. CASE SUMMARY: A young
      patient presented with an inferior dislocation of his right shoulder (erect
      dislocation) after having sustained a motorcycle accident. Conventional
      radiographs revealed the humeral shaft parallel to the scapular spine and an
      anteroinferior position of the humeral head with a large avulsion of the greater
      tuberosity. Preceding arthroscopy showed a complete detachment of the anterior
      labrum and ligament complex (SLAP lesion). After open reduction and internal
      fixation of the greater tuberosity, the capsulolabral complex was reduced and
      securely fixed with three bone anchors at the glenoidal rim. The patient
      recovered well reaching full shoulder function after 5 months and regaining the
      former sports activity level within 9 months after surgery. DISCUSSION:
      Arthroscopy identified the location and extent of an important labral detachment
      that, in combination with the stability testing under anesthesia, proved the need
      for a labral refixation. The literature regarding reported pathology in inferior
      glenohumeral dislocation is reviewed, and the additional information on
      associated soft-tissue lesions by means of arthroscopy are discussed. RELEVANCE:
      No prior case of arthroscopic assessment in inferior glenohumeral dislocation of
      the shoulder has been reported. Recognizing the extent and site of accompanying
      labral detachments contributing to the instability of the joint may enhance our
      knowledge of the full pathology in these dislocations and thus allow an adequate
      surgical treatment.

PMID- 9641447
TI  - Compliance with exercise therapy in treating seniors with knee osteoarthritis.

PMID- 9641448
TI  - Clinical relevance of serial sectioning of sentinel nodes and the detection of
      micrometastatic nodal disease in breast cancer.

PMID- 9641449
TI  - Addressing the axilla in breast cancer, 1998.

PMID- 9641450
TI  - The John Wayne Clinical Research Lecture. Surgical management of melanoma:
      results of prospective randomized trials.

PMID- 9641451
TI  - Serial sectioning of sentinel nodes in patients with breast cancer: a pilot
      study.
AB  - BACKGROUND: Recent reports indicate that the sentinel node, defined as the first
      regional lymph node to receive lymphatic fluid from the breast, accurately
      represents the metastatic status of the primary breast cancer. However, routine
      single section examination of the regional nodes, including the sentinel node,
      underestimates the true incidence of metastases. The goal of this study is to
      determine whether multiple sectioning of sentinel nodes will detect occult
      metastases in operable breast cancer. METHODS: Nineteen patients with invasive
      breast cancers were injected with technetium-99m sulfur colloid solution around
      the tumor or at the biopsy site before lumpectomy and axillary lymph node
      dissection (ALND) or mastectomy. The labeled sentinel lymph nodes (SLND) were
      bivalved, and a central section was taken for hematoxylin and eosin (H & E)
      examination. The sentinel nodes of 13 patients, which were reported to be
      negative for metastases, were serially sectioned at 0.5-mm intervals and stained
      with H & E and a cytokeratin stain, CAM 5.2. RESULTS: In the 13 node-negative
      patients, occult metastases were found in the sentinel nodes of 3 patients (23%).
      Two were seen on H & E and one by cytokeratin stain. The mean numbers of SLND and
      ALND in this series were 2.6 and 12.5, respectively, and the average number of
      sections for the two groups was 14 and 1, respectively. CONCLUSION: Multiple
      sectioning of the sentinel node or nodes detects occult metastases and changes
      the staging of breast cancer.

PMID- 9641452
TI  - Ultrasonographically guided injection improves localization of the radiolabeled
      sentinel lymph node in breast cancer.
AB  - BACKGROUND: Several reports have demonstrated the accurate prediction of axillary
      nodal status (ANS) with radiolocalization and selective resection of sentinel
      lymph nodes (SLN) in breast cancer. To date, no technique has proven to be
      superior in localizing the SLN. METHODS: 1.0 mCi of clear unfiltered
      99mtechnetium sulfur colloid was injected under ultrasonographic (US) guidance
      around the perimeter of the breast lesion (palpable and nonpalpable) or previous
      biopsy site. Resection of the radiolocalized nodes was performed, followed by
      complete axillary lymph node dissection (AXLND). RESULTS: Forty-two breast cancer
      patients underwent SLN biopsy after US-guided radiopharmaceutical injection. The
      SLN was localized in 41 patients (98%). The type of previously performed
      diagnostic biopsy did not influence the ability to localize the sentinel lymph
      node. Pathology revealed nodal metastasis in 7 of the 41 evaluable patients
      (17%). ANS was accurately predicted in 40 of 41 patients (98%). CONCLUSIONS:
      Early experience with radiolocalization and selective resection of SLN in breast
      cancer remains promising. Use of US-guided injection facilitates localization of
      the SLN, perhaps as a result of more accurate placement of the radionuclide
      marker. Use of this technique allowed for effective management of patients
      regardless of tumor size or the extent of prior biopsy, thereby expanding the
      potential number of eligible patients for SLN biopsy.

PMID- 9641453
TI  - Surgical margins and prognostic factors in patients with thick (>4mm) primary
      melanoma.
AB  - BACKGROUND: Randomized trials have demonstrated the efficacy of 1- and 2-cm
      excision margins for thin and intermediate-thickness melanomas, respectively. The
      optimal margin of excision for thick melanomas is still unknown, however. We
      evaluated whether the margins used for intermediate-thickness melanomas can be
      applied safely to thicker lesions. METHODS: The charts of 278 patients with thick
      primary melanomas treated between 1985 and 1996 were retrospectively reviewed.
      Patients with distant metastases at presentation or with follow-up less than 6
      months were excluded. Median follow-up was 27 months. Known melanoma prognostic
      factors and excision margins were evaluated for their impact on local recurrence
      (LR), disease-free survival (DFS), and overall survival (OS). RESULTS: Median
      tumor thickness was 6.0 mm, and 57% were ulcerated. At presentation, 201 patients
      (72%) were node negative and 77 (28%) were node positive (palpable or occult).
      The 5-year OS and DFS rates were 55% and 30%, respectively. The LR rate for all
      patients was 12%. Although nodal status, thickness, and ulceration were
      significantly associated with OS by multivariate analysis, neither LR nor
      excisional margin (<2 cm vs. >2 cm) significantly affected DFS or OS in these
      patients. CONCLUSIONS: Because margins of excision greater than 2 cm do not
      improve LR, DFS, or OS compared to a margin of 2 cm or less, a 2-cm margin of
      excision is adequate for patients with thick melanoma. Because nodal status is a
      significant prognostic factor in these patients, staging by sentinel node biopsy
      should be considered in patients with thick melanomas and clinically negative
      nodal basins to allow proper entry and stratification in adjuvant therapy trials.

PMID- 9641454
TI  - Localized well-differentiated thyroid carcinoma: survival analysis of prognostic
      factors and (131)I therapy.
AB  - BACKGROUND: Recommendations regarding therapeutic use of (131)I for patients with
      well-differentiated thyroid cancer remain controversial. Between 1969 and 1993,
      1171 patients with papillary (including mixed) or follicular thyroid cancer were
      reported to the New Mexico Tumor Registry. Of these, 1075 cases (77.6% female,
      median age 41 years) were available for analysis of survival plots and previously
      recognized risk factors. Extent of operation was documented for 344 patients.
      METHODS: One hundred twenty-seven (37%) patients underwent postoperative (131)I
      ablation. Median follow-up was 99 months. A proportional hazards model was
      constructed using age, gender, stage, histology, and use of radioiodine. The same
      variables plus extent of operation were examined in the smaller group. RESULTS:
      Kaplan-Meier survival estimates at 12 years were 96.2% for patients younger than
      45 years and 68.6% for those older than 45 years. Age, gender, and histology, but
      not stage, were important survival variables (P <.05). Adjusting for other risk
      factors, there was no apparent survival benefit associated with radioiodine
      following clinically appropriate thyroidectomy. Findings from the small group
      mirrored those of the large group. CONCLUSIONS: (131)I may not be as efficacious
      as previously believed for patients with well-differentiated thyroid cancer
      confined to the neck.

PMID- 9641455
TI  - Limited surgery for early gastric cancer in cardia.
AB  - BACKGROUND: Because there are some difficulties with the diagnosis of invasion or
      the endoscopic resection technique, almost all gastric tumors are resected
      surgically. Surgeons now are performing a limited operation for early gastric
      cancer of the upper stomach (EGCUS) without lymph node metastasis. This paper
      discusses and evaluates the surgical technique and the results of the limited
      operation for EGCUS. PATIENTS AND METHODS: Since 1988, a total of 34 patients
      with EGCUS, diagnosed as intramucosal invasion, have undergone a limited
      operation--fundectomy--which includes a limited proximal gastrectomy, a limited
      lymph node dissection, and a procedure preserving the vagal nerve. The surgical
      risk, postoperative complications, and survival rates of the fundectomy patients
      (group A) were compared with those of patients undergoing a total gastrectomy for
      EGCUS (group B). RESULTS: Blood loss was lower in group A (300+/-193 mL) than in
      group B (555+/-316 mL) (P <.05). The incidence of postoperative pancreatic
      fistula also was lower in group A (0%) than in group B (15.0%) (P <.05). All
      patients in both groups (except one who died of a cerebral infarction) are alive
      without recurrence. CONCLUSION: Compared to the results of a total gastrectomy,
      performance of a limited fundectomy for EGCUS decreased surgical risk and
      postoperative complications without decreasing the survival rate.

PMID- 9641457
TI  - Hemangiopericytoma: a 20-year single-institution experience.
AB  - BACKGROUND: Hemangiopericytoma is an uncommon soft tissue sarcoma. We sought to
      evaluate the long-term outcome of a consecutively treated patient cohort with
      hemangiopericytoma. METHODS: The study involved 36 adult patients (older than 16
      years) with hemangiopericytoma treated at The University of Texas M. D. Anderson
      Cancer Center between July 1975 and July 1995. Data on clinicopathologic
      parameters, surgical treatment, adjuvant therapy, disease recurrence, and
      survival were obtained from a review of medical records. RESULTS: The median
      follow-up was 57 months. Twenty-eight patients (78%) underwent complete and
      potentially curative resection of their primary disease. Of the nine patients
      (32%) who had local recurrences, four (57%) had epidural tumors and three (43%)
      had retroperitoneal tumors, but none had extremity tumors. Extremity tumors were
      associated with a significantly prolonged local recurrence-free survival compared
      to tumors at nonextremity anatomic sites (P <.05). Ten patients had recurrences
      at distant sites. Of the 13 patients who experienced any form of disease
      recurrence, four had recurrences after a disease-free interval of more than 5
      years. The 5-year actuarial survival rate for the entire group of 36 patients was
      71%. Noncurative surgical treatment (P=.007) and development of distant
      metastatic disease (P=.013) were associated with shortened survival. CONCLUSION:
      Extended survival is common in hemangiopericytoma patients treated with curative
      intent. However, local and distant recurrences may occur after a prolonged
      disease-free interval, emphasizing the need for long-term follow-up.
      Retroperitoneal and meningeal tumors were associated with higher local recurrence
      rates; therefore, adjuvant therapies should be considered and evaluated for
      tumors at these sites.

PMID- 9641456
TI  - Cell cycle regulation of human pancreatic cancer by tamoxifen.
AB  - BACKGROUND: Clinical trials have suggested a survival advantage for selected
      patients with metastatic pancreatic cancer treated with tamoxifen. We sought to
      identify the molecular mechanism by which tamoxifen inhibits human pancreatic
      cancer cell (HPCC) growth. METHODS: HPCCs were grown in tamoxifen and growth
      inhibition was determined by 3H-thymidine uptake and by the MTT assay; changes in
      cell viability were determined by cell counts. Cell cycle alterations were
      evaluated by FACS, and the induction of apoptosis was evaluated using the TUNEL
      assay. Total cellular RNA was isolated after tamoxifen treatment, and Northern
      blot analysis was performed for p21waf1. RESULTS: Tamoxifen inhibited HPCC growth
      as measured by inhibition of 3H-thymidine incorporation and by the MTT assay.
      However, there was no decrease in the total number of viable cells after 6 days
      of treatment with 10 microM of tamoxifen and no evident apoptosis, confirming the
      absence of a cytotoxic effect. Cell cycle analysis revealed cellular arrest in
      the G0/G1 phase, which correlated with p21waf1 mRNA upregulation in response to
      tamoxifen treatment. CONCLUSIONS: Tamoxifen inhibits HPCC growth by inducing
      G0/G1 arrest with an associated increase in p21waf1 mRNA expression. Tamoxifen is
      an effective inhibitor of HPCC growth in vitro and warrants further in vivo
      study.

PMID- 9641458
TI  - Microsatellite instability in sarcomas.
AB  - BACKGROUND: Microsatellite instability (MIN) has been studied in a variety of
      carcinomas and gynecologic sarcomas, but never in musculoskeletal sarcomas.
      METHODS: We evaluated 16 skeletal and soft tissue sarcomas at nine genetic loci
      from chromosomal regions 1q, 5q, 7q, 12p, 13q, 17p, 19q, and two at 11p--all
      potential regions of interest regarding musculoskeletal sarcomas. RESULTS: MIN
      was identified at one or more loci in seven of the cancers studied (44%). Three
      tumors had more than one locus with MIN and one tumor, a high-grade osteogenic
      sarcoma, had five of nine loci positive for MIN. CONCLUSION: These results
      indicate that musculoskeletal sarcomas show instability in areas inside and
      outside the loci of known oncogenes. Areas of mismatch repair, as heralded by
      MIN, may contribute to the vast heterogeneity of these neoplasms.

PMID- 9641459
TI  - Tamoxifen alters levels of serum insulin-like growth factors and binding proteins
      in postmenopausal breast cancer patients: a prospective paired cohort study.
AB  - BACKGROUND: Recent data suggest that tamoxifen may act by altering serum levels
      of insulin-like growth factors (IGFs) and their binding proteins (BPs). This
      prospective paired cohort study evaluated the influence of tamoxifen on serum
      levels of IGFs and BPs in postmenopausal patients with breast cancer. METHODS:
      Blood was collected from 32 postmenopausal patients with breast cancer before and
      during tamoxifen therapy for at least 6 months. All patients had undergone
      primary surgery. Serum concentrations of IGF-I, IGF-II, BP-1, and BP-3 were
      determined by immunoradiometric assays, and Western ligand blots provided a
      semiquantitative measurement of BP-2, BP-3, and BP-4. Statistical analysis was
      performed by paired Student's t-test. RESULTS: Mean serum IGF-1 level was
      significantly lower after tamoxifen treatment (pretreatment: 116.2 ng/mL+/-13.6
      [SEM] vs. posttreatment: 77.5 ng/mL+/-7.8; P=.003). In contrast, mean IGF-II
      levels increased from 651.5+/-62.2 ng/mL to 812.5+/-35.1 ng/mL during treatment
      (P=.006). Posttreatment levels of BP-1 (92.9 ng/mL+/-7.5) were significantly
      higher compared to the pretreatment values (28.1 ng/mL+/-4.7; P <.001). Serum
      concentration of BP-3 also was elevated (pretreatment: 2228.1 ng/mL+/-145.2 vs.
      posttreatment: 3539.1 ng/mL+/-172.3; P <.001). Densitometric measurements showed
      a similar significant increase in BP-3 (P <.001) as well as BP-4 (P=.017) after
      hormonal therapy. Levels of BP-2 were not influenced by tamoxifen treatment.
      CONCLUSIONS: These significant alterations in serum concentrations of IGFs and
      BPs with tamoxifen therapy suggest that the IGF system is a potential mechanism
      by which tamoxifen exerts its growth inhibitory effect on breast carcinomas.

PMID- 9641460
TI  - Competing causes of death for primary breast cancer.
AB  - BACKGROUND: A patient's likelihood of dying from breast cancer or another cause
      can be assessed with competing risks analyses. METHODS: Data for a cohort of 678
      patients with primary invasive breast cancer accrued from 1971 to 1990, updated
      to 1995, included cause of death (e.g., breast cancer vs. other cause). We
      investigated the effects of age, tumor size, nodal status, ER, PgR, and adjuvant
      therapy (hormones, chemotherapy, radiotherapy) on type of death and time to death
      for patients of all ages and for those over the age of 65 years. RESULTS:
      Although there were no significant univariate differences in breast cancer death
      rates by age group (P=0.94), more patients over the age of 65 years died from
      other causes (41/207 [20%] of those older than 65 years vs. 16/471 [3%] of those
      younger than 65 years; P <.001). In competing risks analyses, older age was
      associated with non-breast cancer death, whereas larger tumor size was associated
      with breast cancer death. PgR was positively, and nodal status negatively,
      associated with survival, regardless of type. In the older patient group, the
      competing risks analyses identified similar effects for age and tumor size; in
      addition, higher ER assay values were less likely to be associated with breast
      cancer death. CONCLUSIONS: With increased lifespan, there will be more breast
      cancer cases in women older than 65 years; we have shown that women in this group
      have more non-breast cancer deaths. It becomes important, then, to delineate
      differential effects of prognostic factors on competing causes of death.

PMID- 9641461
TI  - Efficacy of hyperthermic isolated limb perfusion for extremity-confined recurrent
      melanoma.
AB  - BACKGROUND: Recurrent melanoma of the extremity has been treated by local
      excision, systemic chemotherapy, amputation, or a combination of these
      approaches. Hyperthermic isolated limb perfusion (HILP) provides a method of limb
      preservation through isolation, allowing the administration of chemotherapy in
      higher doses than is possible through systemic treatment. METHODS: An
      experimental group of 59 HILP patients with melanoma recurrences of the extremity
      was studied prospectively. A control group of 248 melanoma patients with similar
      recurrences was excluded from HILP because their recurrences were in non
      extremity locations. The experimental group underwent HILP and excision; the
      control group had excision only. The experimental procedure consisted of vascular
      isolation of the affected extremity and a 1-hour perfusion with melphalan.
      Temperatures were maintained at 40 degrees C in the perfusion circuit. RESULTS:
      The HILP patients had a lower rate of locoregional recurrence (P=.028) and
      demonstrated increased survival (P=.026) compared to the control group. In
      multivariate regression analysis, which included age, ulceration and thickness of
      the primary, and the treatment variable of perfusion, age (P=.02) and perfusion
      for the treatment of recurrence (P=.006) were significant predictors of survival.
      CONCLUSIONS: HILP improves prognosis by sterilizing the treated extremity,
      controlling locoregional disease, and perhaps preventing metastasis, thus having
      a positive impact on overall survival.

PMID- 9641462
TI  - Lymphatic drainage from the skin of the back to retroperitoneal and paravertebral
      lymph nodes in melanoma patients.
AB  - BACKGROUND: Preoperative lymphoscintigraphy (LS) with 99mTc antimony sulphide
      colloid is now part of the routine management of patients with intermediate
      thickness melanoma at the Sydney Melanoma Unit. Over a 13-year period, 1375
      patients have been examined using LS, and we have observed many unusual lymphatic
      drainage pathways, including direct drainage through the body wall to
      retroperitoneal and paravertebral lymph nodes from the skin of the back. The aim
      of this study was to determine the incidence of such drainage in the 542 patients
      who had primary melanoma sites on the posterior trunk. METHODS: The
      lymphoscintigrams performed on these patients were examined for the presence of
      direct lymphatic drainage through the posterior body wall to sentinel nodes in
      the retroperitoneal and paravertebral regions. RESULTS: Lymphatic drainage
      directly through the body wall to such lymph nodes occurred in 14 of these 542
      patients. CONCLUSIONS: Preoperative knowledge of the presence of this lymph
      drainage pattern may influence surgical management, and follow-up investigations
      in these patients can be tailored to ensure that the relevant areas are examined
      with anatomic imaging or F18-FDG PET scans.

PMID- 9641463
TI  - Comparative hypotensive actions of three nonpeptide kappa opioid agonists on
      hippocampus of SHRs and normotensive WKY rats.
AB  - Comparative centrally mediated hypotensive effects of three nonpeptide kappa
      opioid agonist drugs (bremazocine, spiradoline, and U-50,488H) were evaluated in
      chloralose-anesthetized male spontaneously hypertensive rats (SHRs) and in
      normotensive Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats. The drugs were
      administered unilaterally into previously established active hypotensive sites in
      the dorsal hippocampus at doses of 12, 24, and 48 nmol. Each drug produced dose
      related decreases in mean arterial pressure, ranging from -5 to -40% of predrug
      control values, with bremazocine being somewhat more effective than spiradoline,
      which was in turn slightly more active than U-50,488H. The effects were only
      marginally greater in SHRs than in normotensive controls. Each drug caused a
      modest decrease in heart rate, but except for the highest dose of bremazocine,
      the effects were not statistically significant. The onset of hypotension after
      intrahippocampal injection of each agent was approximately 2 min and lasted
      approximately 30 min with U-50,488H and spiradoline and >60 min with bremazocine.
      The responses to all three drugs were completely blocked by prior injection of
      the active hippocampal sites with nor-binaltorphimine (nor-BNI), a selective
      kappa-receptor antagonist. Because bremazocine is more selective for kappa-2
      opioid receptors, whereas U-50,488H and spiradoline favor the kappa-1 subtype,
      the results suggest that drugs active on each of these subtypes should be
      investigated as potential antihypertensives.

PMID- 9641464
TI  - Antagonism of LPS and IFN-gamma induction of iNOS in human saphenous vein
      endothelium by morphine and anandamide by nitric oxide inhibition of adenylate
      cyclase.
AB  - Nitric oxide (NO) production regulates vasodilation in many blood vessels.
      Additionally, constitutive NO release is being associated with positive
      biomedical phenomena, whereas inducible NO synthase (iNOS)-associated NO release
      with detrimental consequences in regard to endothelial inflammatory activities.
      As yet, an important link demonstrating why one is activated over the other is
      not available. Previous studies have demonstrated that morphine and anandamide
      effector processes are coupled to NO release in human endothelial cells (ECs).
      This study now extends this observation in that these endogenous signaling
      molecules may use NO directly to inhibit adenylate cyclase activity. Activation
      of human ECs, obtained from the saphenous vein, with morphine- or anandamide
      stimulated NO release (35 nM and 28 nM, respectively) that peaked within 5 min
      and returned to basal levels within 10 min of agonist stimulation, consistent
      with constitutive NO synthase (cNOS) activation. Significant release of NO from
      ECs stimulated with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma)
      occurred after 2 h after exposure and remained significantly increased over basal
      levels for 24-48 h (28 nM), consistent with iNOS activation. Preincubation of ECs
      with morphine or anandamide before, but not after, the addition of LPS + IFN,
      blocked iNOS activity. Exposure of ECs to the NO donor, SNAP, before the addition
      of LPS + IFN, blocked iNOS induction, whereas preincubation of ECs with
      inhibitors of NOS, before morphine or anandamide exposure, restored LPS + IFN
      induction of iNOS, suggesting a direct impact of NO on the regulation of iNOS
      activity. Morphine and anandamide stimulation of ECs did not stimulate cyclic
      adenosine monophosphate (cAMP) accumulation, whereas a marked increase in cAMP
      was observed in ECs treated with LPS + IFN (8.2 to 33 pmol/mg protein). Treatment
      of ECs with LPS + IFN did not induce cAMP accumulation in ECs treated with
      morphine, anandamide, or SNAP before LPS + IFN exposure. These data suggest that
      cAMP is required for the induction of iNOS in ECs and that NO may directly impair
      adenylate cyclase activity, preventing iNOS activation.

PMID- 9641465
TI  - Nitroglycerin fails to dilate coronary collateral vessels during exercise.
AB  - This study was performed to determine whether nitroglycerin can increase blood
      flow to collateral-dependent myocardium during exercise. Intermittent repetitive
      occlusions of the left circumflex coronary artery (LCX) were used to stimulate
      growth of coronary collateral vessels in seven adult mongrel dogs. Coronary
      pressure distal to the occluder was measured with a long-term implanted
      microcatheter. When sufficient collateral growth had occurred to increase distal
      coronary pressure to >40 mm Hg during occlusion, the artery was permanently
      occluded. Dogs were returned to the laboratory 1 week later for study.
      Measurements were obtained at rest and during treadmill exercise during control
      conditions and after a 300-microg bolus of nitroglycerin (i.v.). Aortic and
      coronary pressures were measured with fluid-filled catheters, whereas myocardial
      blood flow was measured with radioactive microspheres. During control conditions,
      exercise caused significant increases of blood flow in the normal and collateral
      zones with significant decreases in vascular resistance. However, nitroglycerin
      failed to cause a further increase in blood flow to either the normal or the
      collateral-dependent myocardial regions during exercise. Furthermore, neither
      calculated transcollateral resistance (TCR) nor small-vessel resistance (SVR)
      changed significantly in response to nitroglycerin (TCR, 27 +/- 9 mm Hg/ml/min/g
      before nitroglycerin and 27 +/- 6 mm Hg/ml/min/g after; SVR, 43 +/- 5 mm
      Hg/ml/min/g before nitroglycerin and 49 +/- 7 mm Hg/ml/min/g after). The finding
      that the collateral vessels failed to dilate in response to nitroglycerin
      suggests that the nitric oxide system is already maximally recruited during
      exercise.

PMID- 9641466
TI  - Comparison of in vitro cardiovascular function with in vivo echocardiographic
      assessment after long-term administration of cyclosporine to rats.
AB  - Clinical reports indicate that cyclosporine is able to induce heart failure
      without rejection after heart transplantation. This supposition is supported by
      ex vivo animal studies, yet ex vivo studies do not account for the potential of
      counter-regulatory mechanisms, and the clinical observations seem rare in
      comparison with the number of patients treated with cyclosporine. We hypothesized
      that cyclosporine administration to rats would fail to exhibit any effect on
      myocardial contractility in vivo notwithstanding a negative influence ex vivo.
      Transthoracic echocardiographic examinations (two-dimensional targeted M-mode
      tracings) were done in a blinded fashion before and after 1-week treatment of
      rats (10 or 20 mg/kg/day cyclosporine i.p. vs. vehicle). After excision of the
      hearts, contractility and changes in coronary tone were determined ex vivo during
      flow-constant perfusion. Neither cyclosporine nor vehicle treatment resulted in
      changes of echocardiographic parameters (left ventricular diameter, fractional
      shortening). The heart rate was significantly increased in the high-dose
      cyclosporine group. This group showed a significant 38% reduction of
      contractility during the subsequent perfusion ex vivo, whereas low-dose
      cyclosporine or vehicle had no effect on myocardial performance. Vasoconstriction
      did not account for this impairment, because coronary tone was unaltered.
      Cyclosporine, given in doses used in animal studies, impairs myocardial
      contractility ex vivo but fails to exhibit any effect on myocardial performance
      in vivo, possibly because of an increase in sympathetic tone. Considering that
      the denervated transplanted heart in humans is even sensitized to adrenergic
      stimuli, our finding makes unlikely a clinical contribution of cyclosporine to
      failure after orthotopic heart transplantation.

PMID- 9641468
TI  - Effect of the type IV phosphodiesterase inhibitor Ro 20-1724 on catecholamine
      induced alterations in regional vascular resistance and regional blood flow.
AB  - Type IV phosphodiesterase inhibitors have been studied in multiple disease
      processes that commonly afflict patients who are treated with catecholamine
      infusions. To examine whether type IV phosphodiesterases alter catecholamine
      induced changes in systemic and regional hemodynamic parameters, we examined the
      effects of Ro 20-1724 on rats during dobutamine, epinephrine, isoproterenol, and
      norepinephrine infusions. Twenty-six Sprague-Dawley rats received either Ro 20
      1724 or vehicle. After central and regional hemodynamic monitoring was initiated,
      animals received increasing doses of two of the four catecholamines. In the
      absence of catecholamines, Ro 20-1724 infusion caused a significant increase in
      heart rate and a trend toward an increase in superior mesenteric artery blood
      flow. Ro 20-1724 attenuated the increase in blood pressure caused by epinephrine
      but had no effect on the dobutamine-, isoproterenol-, or norepinephrine-induced
      changes in blood pressure. Ro 20-1724 had no effect on catecholamine-induced
      changes in renal, carotid, and hindquarter vascular resistance but did attenuate
      the decrease in superior mesenteric artery vascular resistance caused by
      isoproterenol. Type IV phosphodiesterase inhibition in combination with
      catecholamines has no adverse effects on regional hemodynamics; however, it can
      inhibit the ability of epinephrine infusion to increase blood pressure.

PMID- 9641467
TI  - Doxazosin inhibits proliferation and migration of human vascular smooth-muscle
      cells independent of alpha1-adrenergic receptor antagonism.
AB  - Proliferation and migration of vascular smooth-muscle cells (VSMCs), stimulated
      by a variety of growth factors, play a critical role in the pathogenesis of
      vascular diseases. We found unexpectedly that doxazosin, an alpha1-adrenergic
      receptor antagonist, inhibits serum-stimulated proliferation of cultured human
      VSMCs. Subsequent experiments systematically investigated inhibitory effects of
      doxazosin on mitogenesis stimulated in VSMCs by platelet-derived growth factor
      (PDGF), epidermal growth factor, and G protein-coupled receptor agonists thrombin
      and angiotensin II. Doxazosin attenuated the stimulation of DNA synthesis for
      each of these ligands with median inhibitory concentrations (IC50s) from 0.3 to 1
      microM. PDGF-AB (1 nM) increased cell number; doxazosin inhibited this response
      by 70-80%. Prazosin, a related alpha1-receptor antagonist, had similar but less
      potent effects on inhibiting mitogenesis in these cells. Doxazosin and prazosin
      inhibited PDGF-AB-stimulated and insulin-like growth factor (IGF-I)-stimulated
      migration of VSMCs by approximately 40-50%. These effects of doxazosin were
      likely unrelated to alpha1-receptor blockade because pretreatment of cells with
      phenoxybenzamine, an irreversible alpha1 antagonist, did not change the capacity
      of doxazosin to inhibit of PDGF-stimulated mitogenesis. Also, doxazosin inhibited
      PDGF-stimulated DNA synthesis in NIH 3T3 cells, which do not express alpha1
      receptors. These results suggest that doxazosin is a potent inhibitor of VSMC
      proliferation and migration through a mechanism unrelated to alpha1-receptor
      antagonism.

PMID- 9641469
TI  - Renal vascular responses to angiotensin II in conscious spontaneously
      hypertensive and normotensive rats.
AB  - It has been postulated that exaggerated renal sensitivity to angiotensin II may
      be involved in the development and maintenance of hypertension in the
      spontaneously hypertensive rat (SHR). The purpose of this study was to compare
      the renal vascular responses to short-term angiotensin II infusions (50
      ng/kg/min, i.v.) in conscious SHRs and Wistar-Kyoto (WKY) rats. Renal cortical
      blood flow was measured in conscious rats by using quantitative renal perfusion
      imaging by magnetic resonance, and blood pressure was measured by an indwelling
      carotid catheter attached to a digital blood pressure analyzer. Renal vascular
      responses to angiotensin II were similar in control SHRs and WKY rats.
      Pretreatment with captopril to block endogenous production of angiotensin II
      significantly augmented the renal vascular response to exogenous angiotensin II
      in the SHRs but not in the WKY rats. The renal vascular responses to angiotensin
      II were significantly greater in captopril-pretreated SHRs than in WKY rats
      (cortical blood flow decreased by 1.66 +/- 0.13 ml/min/g cortex in WKY rats
      compared with 2.15 +/- 0.14 ml/min/g cortex in SHR; cortical vascular resistance
      increased by 10.5 +/- 1.4 mm Hg/ml/min/g cortex in WKY rats compared with 15.6 +/
      1.7 mm Hg/ml/min/g cortex in SHRs). Responses to angiotensin II were completely
      blocked in both strains by pretreatment with the angiotensin II AT1-receptor
      antagonist losartan. Results from this study in conscious rats confirm previous
      findings in anesthetized rats that (a) the short-term pressor and renal vascular
      responses to angiotensin II are mediated by the AT1 receptor in both SHRs and WKY
      rats, and (b) the renal vascular responses to angiotensin II are enhanced in SHRs
      compared with WKY rats when endogenous production of angiotensin II is inhibited
      by captopril pretreatment.

PMID- 9641470
TI  - Long-term exposure of human blood vessels to HIV gp120, morphine, and anandamide
      increases endothelial adhesion of monocytes: uncoupling of nitric oxide release.
AB  - Acute exposure of human saphenous vein or internal thoracic artery endothelium to
      either morphine [27.4 +/- 3.7 and 35.4 +/- 4.1 nM nitric oxide (NO),
      respectively] or anandamide (18.3 +/- 2.2 and 24.3 +/- 3.0 nM, respectively)
      results in NO release, whereas exposure to the human immunodeficiency virus
      envelope protein gp120 does not. After the short-term exposure of the vessel
      endothelium, monocyte adherence is diminished with morphine and anandamide
      treatment (jointly by -80%), whereas it is enhanced with that of gp120
      (approximately 40%), indicating that gp120 enhances the ability of the
      endothelium to adhere monocytes. Long-term or continuous exposure of the
      endothelia to all agents results in a significant enhancement of monocyte
      adherence (p < 0.05), which is further increased when exposed to either morphine
      and anandamide plus gp120. This is caused by a desensitization of the endothelium
      to further NO release after the initial exposure to either anandamide or
      morphine. The results serve to indicate that in individuals abusing opiates and
      or cannabinoids, a tissue [i.e., central nervous system (CNS)] viral load may be
      higher, and acquired immunodeficiency syndrome (AIDS) may progress more rapidly
      because monocyte adherence and mobility is significantly increased, indicating a
      higher level of transmembrane migration.

PMID- 9641471
TI  - Facilitation of reflex bradycardia does not contribute to the enhanced
      hypotensive effect of clonidine in aortic barodenervated rats.
AB  - Our previous studies showed that the hypotensive effect of clonidine is enhanced
      in rats with surgically eliminated aortic baroafferents. In this study, we
      investigated whether this effect of clonidine is related to facilitation of
      baroreceptor control of reflex bradycardia. The effects of clonidine on blood
      pressure (BP), heart rate (HR), and baroreflex-mediated decreases in HR
      (baroreflex sensitivity, BRS) were studied in conscious aortic barodenervated
      (ABD) and sham-operated (SO) rats. The slope of the baroreflex curve relating
      increments in mean arterial pressure (MAP) induced by phenylephrine to
      corresponding baroreflex-mediated bradycardic responses was taken as an index of
      BRS. ABD but not the sham operation caused immediate and significant (p < 0.05)
      increases in BP and HR and an impairment of BRS. Two days after ABD, these
      parameters, except the BRS, subsided to near control levels. Starting from
      similar baseline values of BP and HR, clonidine (30 microg/kg, i.v.) elicited
      significantly (p < 0.05) greater decreases in MAP in conscious ABD rats compared
      with SO rats (-23 +/- 2 mm Hg vs. -7 +/- 2 mm Hg). The enhanced hypotensive
      effect of clonidine in ABD rats was associated with a significant reduction in
      baroreceptor-mediated reflex bradycardic responses to increments in BP evoked by
      phenylephrine. The slope of the baroreflex curves that represented the BRS showed
      approximately 40% reduction after treatment with clonidine (baseline BRS, -1.2 +/
      0.06 beats/min/mm Hg; clonidine, -0.73 +/- 0.07 beats/min/mm Hg). On the other
      hand, a threefold lower decrease in BP by clonidine in SO rats was not associated
      with any alteration in BRS. These findings support the hypothesis that aortic
      baroreceptors exert a tonically active restraining influence on centrally
      mediated hypotension. More important, the results do not favor a role for
      facilitation of baroreflexes in the enhanced hypotensive effect of clonidine in
      denervated rats.

PMID- 9641472
TI  - Short-term myocardial uptake of d- and l-sotalol in humans: relation to
      hemodynamic and electrophysiologic effects.
AB  - The myocardial concentration of many cardioactive drugs has been identified as an
      important determinant of their short-term effects in previous studies. Although
      sotalol is frequently administered via short-term intravenous injection, no
      previous studies had sought to correlate its uptake by the heart with its various
      effects. We determined the time course of short-term uptake of d,l-sotalol by
      human myocardium in vivo and investigated the relation between myocardial content
      of sotalol and the short-term hemodynamic, electrocardiographic, and
      electrophysiologic effects of the drug. Sixteen patients received a 20-mg
      intravenous bolus of sotalol at the time of diagnostic cardiac catheterization.
      Myocardial content of d- and l-sotalol (by using a paired transcoronary sampling
      technique) and the short-term hemodynamic and electrophysiologic effects of the
      drug were determined < or = 20 min after injection. Myocardial accumulation of
      sotalol was not enantioselective, proceeded very rapidly (maximal at 0.74 +/-
      0.10 min, representing 2.05 +/- 0.45% of the total injected dose), and was not
      significantly influenced by left ventricular systolic function or the extent of
      coronary artery disease. Approximately one third of peak myocardial content was
      still present 17.5 min after sotalol administration. Maximal effects of the drug
      (reduction in spontaneous heart rate, p < 0.005; reduction in maximal rate of LV
      pressure increase (LV+dP/dtmax, p < 0.005); and prolongation of PR intervals, p <
      0.02) were delayed by approximately 10 min relative to maximal myocardial sotalol
      content. The significant prolongation of AH intervals (p < 0.01) and
      atrioventricular nodal effective refractory periods (p < 0.0002) that was
      observed was also maximal 10 min after administration of sotalol. Thus a
      consistent delay between myocardial sotalol content and the short-term effects of
      the drug was observed. In conclusion, the accumulation of both d- and l-sotalol
      by the human myocardium is more rapid than that of any other agent studied to
      date, with considerable hysteresis between myocardial drug uptake and subsequent
      cardiac effects.

PMID- 9641473
TI  - Relationship between myocardial milrinone content and its acute hemodynamic and
      electrophysiologic effects.
AB  - One of the major determinants of the short-term effects of many cardioactive
      drugs is the concentration of the drug specifically within the myocardium.
      However, no information regarding the disposition of the phosphodiesterase
      inhibitor milrinone in the heart is available. We therefore determined the time
      course of short-term myocardial milrinone uptake from paired transcoronary
      sampling and simultaneous coronary sinus blood flow after a 1-mg intravenous
      bolus in patients undergoing diagnostic cardiac catheterization. In accordance
      with this intention, a sensitive, reproducible method for the determination of
      milrinone in human whole-blood samples was developed. The reverse-phase high
      performance liquid chromatographic method described used a C18 column with UV
      absorbance detection at 326 nm, with a limit of detection of 0.6 ng/ml, and was
      highly reproducible. The short-term hemodynamic and electrophysiologic effects of
      the drug also were determined. Significant increases in spontaneous heart rate
      and LV+dP/dtmax (at constant heart rate) were observed, accompanied by reductions
      in mean arterial pressure, systemic vascular resistance, and PR interval, without
      significant changes in atrioventricular nodal or ventricular effective refractory
      periods. Peak content (1.89 +/- 0.30% of injected dose) was rapidly attained,
      0.56 +/- 0.06 min after milrinone injection. Time of peak effects was
      significantly delayed (7-10 min after injection) relative to time of peak
      myocardial milrinone content. Residual myocardial milrinone content was 69.1 +/-
      5.7% of maximum 12.5 min after injection. It is concluded that both myocardial
      uptake and the onset of positive inotropic effects after intravenous injection of
      milrinone were very rapid. However, there was significant hysteresis between peak
      myocardial content and subsequent hemodynamic effects.

PMID- 9641474
TI  - K-ATP-blocking diuretic PNU-37883A reduces plasma renin activity in dogs.
AB  - We determined the effects of the K-adenosine triphosphate (ATP)-blocking diuretic
      PNU-37883A on plasma renin activity (PRA) in conscious and anesthetized dogs. In
      conscious dogs, oral PNU-37883A (6-60 mg/kg) was less potent than
      hydrochlorothiazide (0.15-1.5 mg/kg) and furosemide (FURO; 0.3-3.0 mg/kg) but
      exhibited high natriuretic efficacy with little kaliuresis. Unlike the standard
      diuretics, PNU-37883A reduced PRA by 46-76%, and its high dose minimally affected
      24-h urinary aldosterone excretion. PNU-37883A, 1 mg/kg i.v., also blunted the
      hyperreninemia induced by 1 mg/kg i.v. FURO. In cannulated dogs, 10 mg/kg i.v.
      PNU-37883A maximally increased fractional Na+ clearance 140% and reduced PRA 76%,
      but these effects were accompanied by a mean 13 mm Hg pressor effect. In
      anesthetized dogs, renal artery-infused PNU-37883A (3 mg/kg/h i.r.a.) increased
      Na+ excretion and reduced renal venous PRA independent of hemodynamics, whereas
      half this dosage selectively reduced renal venous PRA and renin release,
      independent of hemodynamics and natriuresis. These data demonstrate that the K
      ATP blocker diuretic PNU-37883A reduces PRA in dogs after oral, i.v., and i.r.a.
      administration and could be a useful pharmacologic agent for exploring the role
      of K-ATP channels in regulating renin release.

PMID- 9641475
TI  - Changes in platelet function and susceptibility of lipoproteins to oxidation
      associated with administration of aged garlic extract.
AB  - Garlic and some of its organosulfur components have been found to be potent
      inhibitors of platelet aggregation in vitro. Demonstration of their efficacy in
      vivo, however, especially when administered over extended periods, is sparse. We
      recently performed a 10-month study comparing the effect of aged garlic extract
      (AGE) with placebo on the lipid profiles of moderately hypercholesterolemic men.
      In the course of the intervention trial, we examined platelet functions and
      susceptibility of lipoproteins to oxidation in a subgroup of this study
      population. Study subjects supplemented with 7.2 AGE per day showed a significant
      reduction of epinephrine- and, to a lesser degree, collagen-induced platelet
      aggregation but failed to demonstrate an inhibition of adenosine diphosphate
      (ADP)-induced aggregation. Platelet adhesion to fibrinogen, measured in a laminar
      flow chamber at moderately high shear rate, was reduced by approximately 30% in
      subjects taking AGE compared with placebo supplement. A trend toward decreased
      susceptibility of lipoproteins to oxidation also was noted during AGE
      administration compared with the placebo period. We conclude that the beneficial
      effect of garlic preparations on lipids and blood pressure extends also to
      platelet function, thus providing a wider potential protection of the
      cardiovascular system.

PMID- 9641476
TI  - Effects of troglitazone and pioglitazone on cytokine-mediated endothelial cell
      proliferation in vitro.
AB  - We examined whether troglitazone and pioglitazone, antidiabetic
      thiazolidinediones, would directly induce endothelial cell proliferation or
      influence cytokine-driven proliferation in vitro. Monolayers of Balb/c mouse
      aortic endothelial cells were treated with troglitazone or pioglitazone in the
      absence of fetal bovine serum. Endothelial cells also were exposed to varying
      concentrations of basic fibroblast growth factor (bFGF) or insulin with or
      without either thiazolidinedione. After 48 h, 3-[4,5-dimethylthiozol-2-yl]-2,5
      diphenyl tetrazolium bromide (MTT) assays were performed to quantitate
      endothelial cell proliferation by using the various treatment regimens. The data
      demonstrate that the antidiabetic thiazolidinediones troglitazone and
      pioglitazone negligibly affect direct endothelial cell proliferation in vitro.
      Furthermore, troglitazone and pioglitazone significantly inhibit bFGF-induced
      endothelial cell mitogenesis, whereas only high concentrations of troglitazone
      affect insulin-mediated proliferation.

PMID- 9641477
TI  - Effects of amiodarone and desethylamiodarone on the inward rectifying potassium
      current (IK1) in rabbit ventricular myocytes.
AB  - We examined the effects of amiodarone (AMI) and desethylamiodarone (DAM) on whole
      cell inward rectifying potassium current (IK1) in freshly isolated adult rabbit
      ventricular myocytes by using the whole-cell voltage-clamp technique, as an index
      of their effects on resting membrane resistance (Rm). Under control conditions,
      the current showed a strong inward rectification with a maximal inward current
      measured at -130 mV of -26.4 +/- 1.3 pA/pF and a maximal outward current measured
      at -50 mV of 3.5 +/- 0.3 pA/pF The current also exhibit a time-dependent
      activation, with a time constant of activation (tau(a)) that increased with
      depolarization. The maximal slope conductance normalized to cell capacitance was
      0.509 +/- 0.019 nS/pE After exposure to both DAM (50 microM; n = 8) and AMI (50
      microM; n = 7), rapid decrease in inward IK1 was observed. Block was restricted
      almost exclusively to the inward component. DAM caused a significant reduction of
      the maximal inward current (-20.0 +/- 2.0 pA/pF; p < 0.05), whereas AMI induced
      an even greater reduction of the same component (-14.1 +/- 1.2 pA/pF; p < 0.05
      with respect to control and to DAM). The outward component of IK1 was not changed
      by either AMI or DAM (4.0 +/- 0.3 pA/pF and 3.4 +/- 0.4 pA/pF, respectively). AMI
      and DAM also decreased the maximal slope conductance significantly (0.297 +/-
      0.019 nS/pF and 0.421 +/- 0.038 nS/pF, respectively). In addition, AMI but not
      DAM significantly increased the tau(a). However, the voltage dependence of the
      acceleration of tau(a) remained unchanged after both AMI and DAM exposure. These
      results allow us to conclude that AMI may induce a greater increase in the
      resting Rm than its main metabolite. This effect may counterbalance, at least in
      part, the conduction slowing due to its sodium channel-blocking properties.

PMID- 9641478
TI  - Maintained vasodilatory response to cromakalim after inhibition of nitric oxide
      synthesis.
AB  - Activation of vascular smooth-muscle adenosine triphosphate-sensitive potassium
      channels (KATP channels) causes membrane hyperpolarization, reduced entry of Ca2+
      through L-type voltage-gated Ca2+ channels, and subsequent smooth-muscle
      relaxation. Conversely, opening of endothelial KATP channels elicits
      hyperpolarization but may induce Ca2+ influx and stimulation of endothelium
      derived nitric oxide (EDNO) because these cells appear not to possess L-type Ca2+
      channels. We therefore hypothesized that EDNO contributes to KATP channel
      mediated vasodilation. To test this hypothesis, we examined vasodilatory
      responses to the KATP channel opener cromakalim in conscious rats, perfused rat
      tail artery segments, and isolated perfused rat lungs in the presence or absence
      of the EDNO synthesis inhibitor Nomega-nitro-L-arginine (L-NNA). Additionally, we
      compared the effect of cromakalim with the EDNO-dependent dilator bradykinin on
      NO production and intracellular Ca2+ in cultured rat pulmonary artery endothelial
      cells. Vasodilatory profiles to cromakalim were unaffected by L-NNA in conscious
      rats, tail arteries, and isolated lungs. Consistent with these results,
      cromakalim had no apparent effect on either NO synthesis or Ca2+ levels in
      cultured endothelial cells. These data suggest a lack of a role for EDNO in
      contributing to KATP-channel-mediated vasodilation in the rat.

PMID- 9641479
TI  - Combined effects of alcohol and nicotine on cardiovascular performance in a
      canine model.
AB  - Alcohol and tobacco consumption are correlated. Smokers consume more alcohol than
      do nonsmokers, and alcohol consumers smoke more than do teetotalers. The
      independent effects of alcohol and nicotine on the cardiovascular system are well
      documented, but combined effects of short-term administration are unknown. This
      experimental work was designed to study the effects due to short-term
      administration of alcohol and nicotine on cardiovascular system. In phase I, 30
      experiments were performed to study the dose-response curve of both the drugs. In
      phases II and III, 15 dogs were subjected to 30 experiments. In phase II,
      ethanol, 400 mg/kg, was given i.v., followed by nicotine 50 microg/kg, i.v., and
      in phase III, sequence of drug administration was reversed to study the effects
      on hemodynamics and coronary artery blood flow. The dose-response curve
      established the i.v. dose of ethanol, 400 mg/kg, and nicotine, 50 microg/kg.
      Ethanol administration caused a nonsignificant increase in heart rate (HR), mean
      arterial pressure (MAP), left ventricular systolic pressure (LVS), and left
      ventricular mechanical work (LVMW), and a decrease in maximal rate of increase of
      LV pressure per second (dP/dt), stroke volume (SV), and systemic vascular
      resistance (SVR). Left ventricular end-diastolic pressure (LVEDP), pulmonary
      artery mean pressure (PAM), right atrial pressure (RAP), pulmonary vascular
      resistance (PVR), myocardial oxygen consumption (MVO2), and average peak velocity
      of coronary blood flow (APV) had mild significant increases as compared with
      controls. Nicotine significantly increased heart rate, mean arterial pressures,
      LVEDP, and pulmonary artery, pulmonary capillary wedge, and right atrial
      pressures. Nicotine increased dP/dt (2,062-3,188; p < 0.006) and decreased APV (9
      to 8; p < 0.03). Combined ethanol followed by nicotine had synergistic increase
      in HR, SD, MAP, LVS, LVEDP, pulmonary pressures, CO, SV, dP/dt (2,184 > 5,206; p
      < 0.005), MVO2, and LVMW. However, the excitatory effects of nicotine were
      attenuated when ethanol was administered after nicotine (dP/dt, reduced from
      2,058 to 1,653; p < 0.04, and APV increased from 10 to 12; p < 0.02). We conclude
      that ethanol increased APV but had nonsignificant effects on the hemodynamics,
      whereas nicotine reduced the APV and had significant excitatory responses. In
      combination (i.v.), ethanol + nicotine produced significant synergistic
      excitatory effects. On the other hand, the nicotine + ethanol combination
      increased APV and caused attenuation of the excitatory effects of nicotine in
      dogs.

PMID- 9641480
TI  - Depression of efferent parasympathetic control of heart rate in rats with
      myocardial infarction: effect of losartan.
AB  - Heart failure is associated with attenuation of parasympathetic nervous function
      and enhanced renin-angiotensin activity. We tested whether there was a
      dysfunction in the efferent cholinergic neurotransmission in the heart of rats
      with chronic myocardial infarction (MI) and the potential role of angiotensin II
      (Ang II) receptors in such changes. Rats with MI and sham-operation were
      anesthetized, and heart rate (HR) reduction in response to vagal nerve
      stimulation was measured before and after losartan administration (10 mg/kg,
      i.v.) in the presence or absence of physostigmine to inhibit
      acetylcholinesterase. Infarcted rats had an average infarct size (IS) of 38% of
      the left ventricle (LV), depressed LV dP/dtmax, elevated LVEDP, and cardiac
      hypertrophy. Nerve stimulation (1-16 Hz) reduced HR in a frequency-dependent
      manner. The bradycardiac responses were significantly attenuated in infarcted
      versus control rats (p < 0.01), indicating an impaired efferent vagal tone. In
      contrast, the bradycardic response to exogenous acetylcholine was similar in both
      groups, implying an unchanged muscarinic receptor responsiveness in hearts with
      MI. HR response to nerve stimulation was potentiated by losartan in infarcted
      rats by 21 +/- 4 versus 4 +/- 2 beats/min (p < 0.01) but was unaffected in
      control rats. This effect of losartan was inversely related to the extent of
      attenuation of vagally mediated HR reduction. IS was correlated with both the
      extent of attenuation in vagally mediated bradycardia and the effect of losartan.
      In conclusion, the efferent vagal control of HR is attenuated in rats with MI and
      heart failure. This attenuation may be partly due to a presynaptic inhibition of
      acetylcholine release through the tonic activation, by Ang II, of neuronal AT1
      receptors.

PMID- 9641481
TI  - Azimilide causes reverse rate-dependent block while reducing both components of
      delayed-rectifier current in canine ventricular myocytes.
AB  - Most class III antiarrhythmic drugs reduce the rapidly activating component of
      delayed-rectifier current (IKr) without affecting the slowly activating component
      (IKs). Recently the novel antiarrhythmic agent azimilide (NE-10064) was reported
      to enhance IKs at low (nanomolar) concentrations and to block both IKr and IKs at
      higher (micromolar) concentrations. Further to understand the electrophysiologic
      effects of azimilide, we compared its effects on IKr and IKs (by using whole cell
      clamp techniques) and action potentials (microelectrode and perforated-patch
      techniques) on canine ventricular myocytes. A lower azimilide concentration (50
      nM) did not enhance IKs. In contrast, a therapeutic azimilide concentration (2
      microM) was equieffective in reducing IKr (300-ms isochrones) and IKs (3-s
      isochrones) by approximately 40% during depolarizing test pulses, as well as
      reducing IKr (38% decrease) and IKs (33% decrease) tail currents on
      repolarization. Block of IKs was independent of voltage at positive test
      potentials. In action-potential studies, 50 nM azimilide had no effect on the
      action-potential duration (APD), whereas 2 microM azimilide delayed
      repolarization and caused reverse rate-dependent effects on the APD. Whereas the
      extent of APD prolongation by azimilide was not correlated with the drug-free
      APD, azimilide preferentially exaggerated the APD-rate relationship of myocytes
      displaying the steepest APD-rate relationship under drug-free conditions. In
      conclusion, therapeutic concentrations of azimilide that cause comparable
      reduction of canine ventricular IKr and IKs exert reverse rate-dependent effects,
      which are dependent on the steepness of the APD-rate relationship.

PMID- 9641483
TI  - Arterial vasodilation and vascular connective tissue changes in spontaneously
      hypertensive rats.
AB  - Arterial hypertrophy in response to hypertension includes increases in the
      connective tissue proteins elastin and collagen. Regression of arterial
      hypertrophy depends not only on blood pressure normalization but also on the
      specific antihypertensive treatment. Consequently, each drug class may exert an
      influence on connective tissue proteins. We evaluated the arterial connective
      tissue response of 16-week-old spontaneously hypertensive rats (SHRs) to
      treatment with minoxidil, 120 mg/L, drinking water for 10 weeks. Despite a
      decrease in blood pressure, minoxidil had no effect on arterial weight or
      collagen content but increased elastin content in the abdominal aorta, renal, and
      superior mesenteric arteries. The increase in elastin content in the abdominal
      aorta and superior mesenteric artery was accompanied by a decrease in tissue
      elastase activity. Thus the minoxidil-induced increase in arterial elastin
      content may be related to a direct effect of the drug to decrease elastase
      activity in these tissues.

PMID- 9641482
TI  - Baroreflex-mediated bradycardia is blunted by intravenous mu- but not kappa
      opioid agonists.
AB  - To assess the cardiovascular effects of systemically administered opioid
      agonists, changes in blood pressure and heart rate were observed after
      intravenous (i.v.) administration of U50,488H (trans-3,4-dichloro-N-[2-(1
      pyrrolidinyl) cyclohexyl]benzeneacetamide), a selective kappa-opioid receptor
      agonist, and DAMGO (D-Ala2, N-Me-Phe4, Gly5-ol), a selective mu-opioid-receptor
      agonist. Intravenous administration of U50,488H (1.2 mg/kg) and DAMGO (0.3 mg/kg)
      to the awake sheep resulted in an immediate increase in blood pressure. The
      pressor response to U50,488H was accompanied by an increase in heart rate. In
      contrast, there was no accompanying change in heart rate in response to DAMGO. We
      hypothesized that the lack of a reflex bradycardia to the pressor responses of
      both the mu- and kappa-opioid-receptor agonists was due to a blunting of
      baroreflex-mediated bradycardia. The reflex bradycardia to norepinephrine (0.6
      microg/kg/min) was significantly reduced in the presence of DAMGO but not
      U50,488H. In view of the lack of effect of U50,488H on the baroreflex, we further
      hypothesized that the tachycardia it elicited was due to an increase in
      sympathetic activity. Pretreatment with propranolol (0.1 mg/kg) completely
      blocked the tachycardia elicited by U50,488H. These data suggest that the lack of
      a reflex bradycardia to the pressor response of DAMGO is due to a blunting of
      baroreflex-mediated bradycardia. In contrast, the increase in heart rate caused
      by U50,488H is mediated by sympathetic activation of the heart.

PMID- 9641484
TI  - Cardiovascular effects of nepicastat (RS-25560-197), a novel dopamine beta
      hydroxylase inhibitor.
AB  - Nepicastat (RS-25560-197) is a novel, selective, and potent inhibitor of dopamine
      beta-hydroxylase, which modulates catecholamine levels (reduces norepinephrine
      and elevates dopamine) in cardiovascular tissues. This study was designed to
      evaluate the cardiovascular effects of nepicastat. Acute oral administration of
      nepicastat (0.3, 1, 3, 10, and 30 mg/kg) produced attenuation of the pressor and
      positive chronotropic responses to preganglionic sympathetic nerve stimulation
      (about twofold to sixfold shift in the frequency-response curve) in pithed
      spontaneously hypertensive rats (SHRs). In inactin-anesthetized SHRs, the
      antihypertensive effects of nepicastat (3 mg/kg, i.v.) were accompanied by a
      significant decrease in renal vascular resistance (38%), a tendency toward an
      increase in renal blood flow (22%), and no adverse effects on urine output and
      Na/K excretion. In conscious, unrestrained, telemetry-implanted SHRs, nepicastat
      (30 and 100 mg/kg/day for 30 days) produced dose-dependent decreases in mean
      arterial blood pressure (peak decrease of 20 and 42 mm Hg, respectively) without
      evoking reflex tachycardia. Long-term, concurrent administration of nepicastat
      (30 mg/kg/day, p.o.) and a subthreshold dose of enalapril (1 mg/kg/day, p.o.)
      produced greater antihypertensive effects than those produced by nepicastat
      alone. In normal dogs, nepicastat (5.0 mg/kg, p.o., b.i.d., for 4.5 days) blunted
      the positive chronotropic and pressor response to tyramine. These findings
      suggest that nepicastat functionally modulates sympathetic drive to
      cardiovascular tissues and may be of value in the treatment of cardiovascular
      disorders associated with overactivation of the sympathetic nervous system such
      as hypertension and congestive heart failure.

PMID- 9641485
TI  - Inhibition of myocardial lesions in the JCR:LA-corpulent rat by captopril.
AB  - The JCR:LA-cp rat is a unique strain that, if homozygous for the autosomal
      recessive cp gene, is obese and exhibits the metabolic syndrome of insulin
      resistance, hyperinsulinemia, and hypertriglyceridemia. Obese male rats
      spontaneously develop advanced atherosclerosis and ischemic myocardial lesions.
      The angiotensin-converting enzyme inhibitor, captopril, was administered to obese
      rats at 30 mg/kg body weight from 6 to 39 weeks of age. There were no significant
      changes in food consumption or body weights of the treated animals. Insulin
      sensitivity was not improved. Plasma insulin levels were unaltered, but the
      volume density of the islets of Langerhans was halved, reflecting both reduced
      hyperplasia and a more normal islet structure. Triglyceride concentrations were
      not reduced, but unesterified cholesterol and cholesteryl esters decreased by 50%
      and 34%, respectively (p < 0.01). The impaired nitric oxide-mediated vascular
      relaxation of the obese rats was not improved, and the relaxant sensitivity to
      acetylcholine as indicated by the median effective concentration (EC50) was
      reduced. In vitro, captopril significantly reduced the basal tension of aortic
      rings from untreated rats, antagonized the contractile effects of norepinephrine,
      and induced complete relaxation of the contraction in response to 10(-7) M
      norepinephrine. The severity of spontaneous, raised atherosclerotic lesions of
      the aortic arch at age 39 weeks was not significantly decreased by captopril
      treatment. In contrast, the frequency of ischemic myocardial lesions was reduced
      by 78% (p < 0.01). The protective effects of captopril on the heart and pancreas
      in this animal model of type II diabetes and atherosclerosis are probably the
      result of its bradykinin-enhancing effects.

PMID- 9641486
TI  - Dopamine D4 receptors and the risk of cigarette smoking in African-Americans and
      Caucasians.
AB  - An understanding of why people smoke cigarettes can have an important impact on
      smoking prevention and cessation. People smoke cigarettes to maintain nicotine
      levels in the body, and nicotine has been implicated in the stimulation of brain
      reward mechanisms via central neuronal dopaminergic pathways. In this study, we
      evaluated the association of smoking and smoking cessation with a dopamine D4
      receptor 48-bp variable nucleotide tandem repeat polymorphism in which the seven
      repeat allele (D4.7) reduces dopamine affinity. Smokers (n = 283) and nonsmokers
      (n = 192) were recruited through local media for a case-control study of smoking.
      After giving informed consent and answering a behavioral questionnaire, smokers
      underwent a single minimal-contact session of smoking cessation counseling and
      then were followed for up to 1 year. The frequency of the dopamine D4 receptor
      genetic polymorphism using PCR was determined, and individuals were classified by
      the number of repeat alleles (two to five repeats as S and six to eight repeats
      as L). Persons with those genotypes including only S alleles (homozygote S/S)
      were compared with those with at least one L allele (heterozygote S/L and
      homozygote L/L). Chi2 tests of association, Fisher's exact test, and Student's t
      test were used. Ps were two-tailed. The data show that African-Americans (n = 72)
      who had at least one L allele had a higher risk of smoking (odds ratio, 7.7; 95%
      confidence interval, 1.5-39.9; P = 0.006), shorter time to the first cigarette in
      the morning (P = 0.03), and earlier age at smoking initiation (P = 0.09) compared
      with homozygote S/S genotypes. After smoking cessation counseling, none of the
      African-American smokers with an L allele were abstinent at 2 months, compared
      with 35% of the smokers who were homozygote S/S (P = 0.02). The analysis of
      Caucasians (n = 403) did not suggest a similar smoking risk for the D4 genotypes
      (odds ratio, 1.0; 95% confidence interval, 0.6-1.6; P = 0.90), or smoking
      cessation (P = 0.75). Although the number of African-Americans is small, this
      study is consistent with the hypothesis that the L alleles increase the risk of
      smoking because these individuals are prone to use nicotine to stimulate synaptic
      dopamine transmission. If replicated, the data indicate that a single minimal
      contact session of cessation counseling, similar to what is typically provided in
      primary care physician offices, is ineffective in African-American smokers who
      have at least one L allele. The finding of an effect for these polymorphic loci
      in African-Americans, but not Caucasians, suggests that the variable nucleotide
      tandem repeat studied here is a marker for another polymorphic site in African
      Americans, but not in Caucasians.

PMID- 9641487
TI  - Can strategies used by statewide tobacco control programs help smokers make
      progress in quitting?
AB  - Many states have recently adopted programs to encourage smokers to quit. Here, we
      seek evidence that strategies generally used by these programs have the potential
      to influence smoking cessation. In California, 1,736 smokers from a population
      based telephone survey were interviewed in 1990 and 1992. We examined the
      association of demographic and program-related variables (reporting of work area
      smoking bans; belief in the harmfulness of environmental tobacco smoke, including
      in-home smoking restrictions; and quitting assistance) with quitting progress.
      Smokers were categorized into levels in a previously developed Quitting
      Continuum, which considers their addiction level and quitting history. Smokers in
      each higher continuum category had an increased likelihood of future successful
      cessation. Smokers progressed if they were at a higher continuum level in 1992
      than in 1990. College graduates showed 2.3 times more progress than did high
      school dropouts. Smokers reporting work area smoking bans showed 1.6 times more
      progress than did workers not reporting such restrictions. Smokers with the
      strongest beliefs (home smoking restrictions) regarding the harmfulness of
      environmental tobacco smoke showed 3.4 times more progress than smokers with no
      belief. Smokers who reported having some form of cessation assistance showed 3.0
      times more progress. The more program-related factors were reported, the higher
      the rate of progress was: 13.1% for those reporting no factors, 23.4% for one
      factor, and 40.6% for two or more. These results suggest but do not prove that
      strategies promoted by statewide tobacco control programs can potentially be
      effective and that these efforts should be continued and expanded.

PMID- 9641488
TI  - Reduced DNA repair capacity in head and neck cancer patients.
AB  - Head and neck cancers (HNCs) are malignancies that can be induced by tobacco use,
      although host-specific factors such as the DNA repair capacity (DRC) may modulate
      individual susceptibility to tobacco carcinogenesis. To test the hypothesis that
      genetically determined DRC modulates HNC susceptibility, we measured the DRC in
      the peripheral blood lymphocytes of 55 patients with newly diagnosed, previously
      untreated HNC and 61 healthy controls by the host-cell reactivation assay using a
      reporter gene damaged by benzo(a)pyrene diol epoxide, an ultimate tobacco-related
      carcinogen. The mean DRC was significantly lower in cases (8.6%) than it was in
      controls (12.4%; P < 0.001). The DRC was an independent risk factor for HNC (P <
      0.01); those in the middle and lowest tertiles of DRC had increased odds ratios
      [2.17 (95% confidence interval, 0.74-6.39) and 4.27 (confidence interval, 1.45
      12.5), respectively] for HNC. These findings suggest that individuals with
      reduced DRC may be at increased risk of developing HNC.

PMID- 9641489
TI  - Exfoliated oral cell messenger RNA: suitability for biomarker studies.
AB  - The efficacy of chemoprevention trials can be improved by the use of biomarkers
      of carcinogenesis that serve as surrogate end points. The aim of this study was
      to assess the perspectives of using mRNA isolated from oral exfoliated cells for
      biomarker research in chemoprevention of upper aerodigestive tract cancer. When
      using reverse transcription-PCR in combination with Southern blotting and
      hybridization, it was possible to detect transcripts from only five cells. With
      the quantitative RNase protection assay, we could only detect highly abundant
      transcripts. The integrity of the RNA was verified by Northern blotting, which
      showed a variable degree of degradation, depending on the gene studied.
      Interestingly, although specific transcripts were found to be intact to a certain
      extent, the rRNA appeared to be completely degraded, suggesting that a specific
      protein synthesis shut-off mechanism exists in terminally differentiated oral
      epithelial cells. Altogether, this differential RNA degradation makes accurate
      measurement of transcript levels of most genes, as determined in exfoliated oral
      cells, unreliable. Because this RNA degradation process is likely to start before
      the cells are shed from the tissue, the results of measurements of transcript
      levels in biopsies of oral tissue should be interpreted with caution.

PMID- 9641490
TI  - Short-term follow-up after endoscopic mucosectomy of early esophageal cancer and
      aldehyde dehydrogenase-2 genotype in Japanese alcoholics.
AB  - The risk of the future development of primary esophageal cancer after endoscopic
      esophageal mucosal resection of esophageal cancer is not known; hence, there are
      no established guidelines for follow-up surveillance programs. Simultaneous
      occurrence of multiple cancers associated with esophageal cancer is common among
      heavy drinkers who have the inactive form of aldehyde dehydrogenase-2 (ALDH2) as
      a risk factor. Thirty-four Japanese male alcoholics with intraepithelial or
      mucosal squamous cell carcinoma in the esophagus were treated by endoscopic
      esophageal mucosal resection, followed by endoscopy and esophageal iodine
      staining, to find the additional development of primary esophageal cancer.
      Primary esophageal squamous cell carcinoma was detected in nine patients (26.5%)
      at 3-21 months after the first cancer diagnosis. Cancer occurred more frequently
      in patients with inactive ALDH2 than it did in those with active ALDH2 [42.1% (8
      of 19) versus 6.7% (1 of 15), P = 0.047], and it occurred more frequently in
      those with multiple esophageal cancers than it did in those without them [60.0%
      (6 of 10) versus 12.5% (3 of 24), P = 0.009]. Kaplan-Meier estimates of the
      proportions of patients with additional primary esophageal cancers showed that
      patients with inactive ALDH2 (P = 0.024) or multiple esophageal cancers (P =
      0.007) had a significantly increased likelihood of the development of additional
      cancer. Close follow-up examinations using endoscopy and iodine staining are
      needed for such high-risk patients.

PMID- 9641491
TI  - Anthropometric and hormone effects of an eight-week exercise-diet intervention in
      breast cancer patients: results of a pilot study.
AB  - To assess the feasibility of an exercise-diet intervention in sedentary,
      overweight breast cancer patients, we conducted a pilot 8-week intervention.
      Recruitment letters and interest surveys were sent to 99 stage 1 or 2 breast
      cancer patients, ages 25-75 years, who were identified through two Seattle breast
      surgery practices and the University of Washington Breast Clinic. Ten patients
      were eligible and interested and were enrolled in the intervention, which
      consisted of thrice-weekly monitored aerobic exercise sessions and a low-fat (20%
      of calories from fat) diet. Nine patients completed the program; all adhered well
      to the intervention and data collection protocol. The patients, ages 40-74 years,
      lost, on average, 2.6 pounds of body weight, 3.4 cm in waist circumference, 4.6
      cm in hip circumference, 2.3% body fat, 3.3 systolic blood pressure points, 0.67
      diastolic blood pressure points, and 4.0 pulse beats/min, and they gained an
      average of 2.3% lean mass. Slight, nonsignificant decreases were observed in
      serum concentration of total and free estradiol, estrone sulfate, total
      testosterone, androstenedione, and dehydroepiandrosterone. These pilot data
      indicate that breast cancer patients are highly motivated to join and adhere to
      an intense exercise-diet intervention and can experience significant measurable
      changes in anthropometric and fat mass measures.

PMID- 9641492
TI  - Association between high-density lipoprotein cholesterol and breast cancer varies
      by menopausal status.
AB  - A nested case-control study was conducted to investigate the hypothesis that
      women with high levels of high-density lipoprotein cholesterol (HDL-C) are at an
      increased risk of breast cancer. The source population was a cohort of 95,000
      women enrolled in the Kaiser Permanente Medical Care Program who underwent a
      routine multiphasic health examination between 1964 and 1971. From the more than
      2,000 breast cancer cases diagnosed in this cohort, 200 cases were randomly
      selected for this study. For each case, one control who matched on age and date
      of examination was chosen. Lipid and lipoprotein levels were measured in archived
      serum samples collected at the time of the women's examinations. Breast cancer
      risk factor information was obtained from questionnaires completed by the women
      when their blood was drawn and was supplemented with information from medical
      records. HDL-C levels were not significantly different between the cases and
      controls overall; however, a statistically significant interaction between the
      HDL-C level and menopausal status at diagnosis was detected. Premenopausal cases
      had mean HDL-C levels 3.48 mg/dl lower than matched controls [95% confidence
      interval (CI), -7.05, 0.09], whereas postmenopausal cases had levels 2.05 mg/dl
      higher than controls (95% CI, -0.94, 5.03). In multivariate conditional logistic
      regression analyses, the odds ratio associated with each 1 mg/dl increase in HDL
      C was 0.96 (95% Cl, 0.93-1.0) for premenopausal women and 1.02 (95% CI, 0.99
      1.05) for postmenopausal women. Although many breast cancer risk factors are
      associated with high HDL-C, the relationship between breast cancer and HDL-C was
      independent of other factors evaluated.

PMID- 9641493
TI  - Relative abundance of organochlorine pesticides and polychlorinated biphenyls in
      adipose tissue and serum of women in Long Island, New York.
AB  - Some organochlorine pesticides (OCPs) and PCBs are under investigation as
      possible risk factors for breast cancer because of their estrogenic properties
      and widespread presence in the environment. It is important to know whether
      adipose tissue used by some investigators and serum assays used by others can
      provide comparable information on body burden. Concentrations of seven OCPs or
      their breakdown products as well as 14 PCB congeners were measured in the adipose
      tissue and serum of 293 women enrolled as controls in a case-control study of
      environmental factors for breast cancer in Long Island, New York, a high-risk
      region. Adipose OCP/PCB levels were measured using a supercritical fluid
      extraction method developed by the authors. 1,1-Dichloro-2,2-di(4
      chlorophenyl)ethylene (p,p'-DDE) was detected in all adipose and serum samples;
      two chlordane derivatives, beta-hexachlorocyclohexane (a lindane isomer) and
      hexachlorobenzene, were detected in at least 92% of adipose samples. The di-ortho
      hexachlorinated PCB congeners 2,4,5,2',4',5'-hexachlorobiphenyl and
      2,3,4,2',4',5'-hexachlorobiphenyl were detected in all adipose and over 98% of
      serum samples. 1,1-Dichloro-2,2-di(4-chlorophenyl)ethylene comprised 77% of total
      pesticide residues in adipose and 71% in serum. 2,4,5,2',4',5'-Hexachlorobiphenyl
      comprised 24% of adipose and 21% of serum PCBs. The relative concentration
      patterns of the 14 PCB congeners were similar to those reported in other human
      studies and were also typical of patterns reported in environmental samples from
      various biota, including mammals and birds, but differed substantially from
      patterns reported in occupationally exposed workers. All adipose-serum
      correlations for pesticides and most PCBs were statistically significant. Either
      serum or adipose OCP/PCB levels of a variety of environmental organochlorine
      compounds may serve as useful biomarkers of body burden.

PMID- 9641494
TI  - A subset of metastatic human colon cancers expresses elevated levels of
      transforming growth factor beta1.
AB  - Although transforming growth factor (TGF)-beta1 is a potent growth inhibitor of
      normal epithelial cells including colonocytes, TGF-beta1 has also been implicated
      as an enhancer of colon cancer metastasis. Decreasing TGF-beta1 protein levels in
      the metastatic U9 colon cancer cell line by antisense methodology decreased both
      U9 cell metastasis to the liver and s.c. tumor formation in a nude mouse system,
      and the tumors that did arise had regained TGF-beta1 expression (F. Huang et al,
      Cell Growth Differ., 6: 1635-1642, 1995). In addition, in a clinical
      immunohistochemistry study, colon cancers with elevated TGF-beta1 protein levels
      were found to be 18 times more likely to recur as distant metastases than colon
      cancers expressing low TGF-beta1 levels, after resection of the primary tumor (E.
      Friedman et al, Cancer Epidemiol. Biomark. Prev., 4:549-554, 1995). Because both
      studies implicated TGF-beta1 in colon cancer metastasis, we wished to know
      whether a selection bias for TGF-beta1 was maintained in metastatic cells or was
      only a property of the primary site tumors that were likely to metastasize. TGF
      beta1 levels were measured using two different antibodies in paired primary site
      cancers and their metastases by immunohistochemistry and, in selected cases, by
      Western blot analysis. In 16 of 21 cases (76%) with antibody G and 23 of 31 cases
      (74%) with antibody P, higher expression of TGF-beta1 was found in colon cancer
      cells invading local lymph nodes compared with primary site colon cancer cells,
      or (2 and 6 cases, respectively) high TGF-beta1 expression in the primary site
      cancer was maintained in invasive cells. Analysis by Western blotting using both
      antibodies also demonstrated that higher levels of TGF-beta1 protein were found
      in metastases compared with the primary site tumor or normal tissue. Additional
      cases of paired primary site colon cancer, local lymph node metastases, and
      cancer cells metastasizing to distant sites were examined. In six of eight such
      cases (75%), TGF-beta1 levels were increased in both invasive cell populations
      compared with the primary site cancer (five cases), or high levels in the primary
      site cancer were maintained in the metastatic cells (one case). These data
      suggest that TGF-beta1 plays a role in promoting colon cancer metastasis
      throughout the metastatic process in roughly 75% of cases. TGF-beta1 may increase
      metastasis by paracrine mechanisms, such as suppression of local immune response
      or increased angiogenesis, as was seen with the U9 cell line. In those cancers
      with nonmutated TGF-beta receptors and nonmutated smad proteins like U9 cells,
      TGF-beta1 could also act in an autocrine manner to increase invasion by
      increasing cell motility (Hsu et al., Cell Growth Differ., 5: 267-275, 1994).

PMID- 9641495
TI  - Heterogeneity of guanylyl cyclase C expressed by human colorectal cancer cell
      lines in vitro.
AB  - In humans, guanylyl cyclase C (GCC) is expressed by mucosal cells lining the
      intestine, from the duodenum to the rectum, but not by extraintestinal tissues.
      Expression of GCC persists after mucosal cells undergo neoplastic transformation,
      and this protein has been identified in all primary and metastatic colorectal
      tumors examined to date, suggesting that GCC may be a highly specific biomarker
      for colorectal cancer. The utility of GCC as a diagnostic biomarker and
      therapeutic target is predicated, in part, on defining the variability of its
      expression in colorectal cancer cells. Similarly, the utility of this biomarker
      to define tumor burden in diagnosing, staging, and postoperative surveillance of
      patients is predicated on quantifying GCC expression in cancer cells in tissues
      and blood. The present studies examined the heterogeneity of GCC expression in
      eight human colorectal carcinoma cell lines in vitro representing the full
      spectrum of cytological differentiation. Quantification of GCC expression by
      ligand binding and stimulation of cGMP accumulation demonstrated that functional
      GCC expression is heterogeneous in different colorectal cancer cell lines.
      Qualitative reverse transcription (RT)-PCR demonstrated that all colorectal
      cancer cells examined expressed GCC mRNA. However, GCC expression varied 100-fold
      in different colorectal cancer cell lines, determined by a novel quantitative RT
      PCR assay. Functional and molecular expressions of GCC were unrelated to the
      differentiation state of cancer cells. These studies suggest that GCC is
      heterogeneously expressed by colorectal cancer cells in vitro and suggest a role
      for quantitative RT-PCR analysis in the development of diagnostic tests using GCC
      as a biomarker for metastatic colorectal cancer.

PMID- 9641497
TI  - Predictors of dietary heterocyclic amine intake in three prospective cohorts.
AB  - Cooking meat creates heterocyclic amines (HCAs) through pyrolysis of amino acids
      and creatinine. Although recognized as mutagenic, the etiological role of HCA in
      human cancer is unclear, due to the lack of information on the effect of typical
      food cooking methods on HCA concentrations and on variation in HCA exposure in
      populations. We estimated overall daily dietary HCA intake and variation in
      intake between individuals, using recent data on HCA concentrations in various
      meats prepared by cooking methods, temperatures, and times common in United
      States in the 1990s. Random samples of 250 participants from each of three large
      prospective cohorts were mailed a questionnaire to assess frequency of
      consumption, cooking method, and typical outside appearance of pan-fried,
      broiled, and grilled or barbecued chicken, fish, hamburger, and steak; fried,
      microwaved, and broiled bacon; fried sausage; roast beef; and homemade gravy. The
      2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP), and 2-amino-3,4,8
      trimethylimidazo[4,5,f]quinoxaline (DiMeIQx) concentrations, measured in
      composite samples by solid-phase extraction and high-performance liquid
      chromatography, were assigned to each food, cooking method, and doneness level.
      The dietary reports showed approximately 30-fold relative variation in 2-amino
      3,8-dimethylimidazo[4,5-f]quinoxaline intake, 20-fold for 2-amino- -methyl-6
      phenylimidazo[4,5-b]pyridine, and over 110-fold for 2-amino-3,4,8
      trimethylimidazo[4,5,f]quinoxaline, when the 10th and 90th percentiles of HCA
      intake were compared (90th/10th percentile value). These reported variations in
      HCA exposure among participants in these three large cohorts indicates that
      estimation of HCA intake and determination of association with disease risk are
      feasible, if additional information on meat cooking methods is obtained.

PMID- 9641496
TI  - K-ras mutation in focal proliferative lesions of human pancreas.
AB  - The K-ras gene is mutated in > or =75% of human pancreatic adenocarcinomas and in
      a number of hyperplastic ductal lesions from noncarcinoma patients. In this
      study, the incidence of K-ras mutation was determined in a spectrum of focal
      proliferative pancreatic lesions to evaluate their preneoplastic significance.
      PCR-based mutation-enriched RFLP analysis was used to identify mutations in codon
      12. Immunostaining for Ki67 and p53 was also performed. Forty-seven % of
      intraductal nonpapillary hyperplasias (8 of 17) contained codon 12 mutations, as
      did 55% of adenomatoid hyperplasias (6 of 11). This rate increased to 61% in
      papillary hyperplasias (27 of 44) and to 78% when there was severe dysplasia (7
      of 9). The fraction of cells staining for the Ki67 proliferation marker showed a
      general correlation with the rate of K-ras mutation. Nuclear staining for p53
      protein was seen only in two ductal lesions with severe dysplasia. No mutations
      were found in normal acinar tissue (n = 38), squamous metaplasia (n = 13), ductal
      complexes (n = 8), or focal acinar cell dysplasia (n = 5). There seemed to be a
      general correlation of proliferative potential with the presence of K-ras
      mutation in ductal lesions. However, because of the high prevalence of lesions
      with K-ras mutations, we conclude that this mutation alone cannot be taken as
      proof of significant risk for progression to carcinoma. Efforts to use the
      presence of K-ras mutations in DNA harvested from pancreatic juice or duodenal
      aspirates as an approach for diagnosis of occult pancreatic carcinoma seem
      vulnerable to a high false-positive rate.

PMID- 9641498
TI  - CG island methylation changes near the GSTP1 gene in prostatic intraepithelial
      neoplasia.
AB  - Prostate intraepithelial neoplasia (PIN) is a purported prostate cancer precursor
      lesion and a candidate biomarker for efficacy assessment in prostate cancer
      chemoprevention trials. Loss of expression of the pi-class glutathione S
      transferase enzyme GSTP1, which is associated with the hypermethylation of
      deoxycytidine residues in the 5'-regulatory CG island region of the GSTP1 gene,
      is a near-universal finding in human prostate cancer. GSTP1 expression was
      assessed by immunohistochemistry in 60 high-grade PIN samples adjacent to and
      distant from prostate adenocarcinoma. Whereas abundant enzyme polypeptide
      expression was evident in all normal prostatic tissues, all samples of high-grade
      PIN and adenocarcinoma were completely devoid of GSTP1. DNA from 10 high-grade
      PIN lesions was analyzed for GSTP1 CG island methylation changes using a PCR
      technique targeting a polymorphic (ATAAA)n repeat sequence in the promoter region
      of the GSTP1 gene. Somatic GSTP1 CG island methylation changes were detected in
      DNA from 7 of the 10 PIN lesions. Allele discrimination was possible for 5 of the
      10 DNA samples: 2 of the 5 samples exhibited DNA methylation changes at both
      alleles; whereas 3 samples displayed no DNA methylation changes at either allele.
      GSTP1 CG island methylation changes were present in each of the five homozygous
      samples. Hypermethylation of the 5'-regulatory region of the GSTP1 gene may serve
      as an important molecular genetic biomarker for both prostate cancer and PIN. The
      finding of frequent GSTP1 methylation changes in PIN and prostate cancer supports
      a role for PIN lesions as a prostate cancer precursor and may provide insight to
      the molecular pathogenesis of prostate cancer.

PMID- 9641499
TI  - The association of plasma micronutrients with the risk of cervical dysplasia in
      Hawaii.
AB  - Limited data from hematological studies suggest that certain nutrients, including
      carotenoids, tocopherols, and vitamin C, may protect against malignant change in
      cervical tissue. Recognizing that human papillomavirus (HPV) infection induces
      most neoplastic transformation of cervical tissue, the authors conducted a case
      control study to examine the association of plasma micronutrient concentrations
      with the risk of cervical dysplasia after careful adjustment for HPV infection,
      using a sensitive and reliable HPV detection method. The sample included 147
      multiethnic women, between 18 and 65 years of age, with biopsy-confirmed squamous
      intraepithelial lesions (SILs) of the cervix and 191 clinic controls identified
      between 1992 and 1996. Cases were identified through cytology and pathology logs
      in three clinics on Oahu, Hawaii. Controls were selected randomly from admission
      logs of the participating clinics. In-person interviews were conducted in the
      subjects' homes, and a fasting blood sample was drawn to measure plasma levels of
      lutein, lycopene, cryptoxanthin, total carotene, retinol, tocopherol, ascorbic
      acid, and cholesterol. The presence and type of HPV was determined in exfoliated
      cell samples using PCR dot blot hybridization. Mean plasma lycopene, total
      cryptoxanthin, and alpha-cryptoxanthin levels were lower among cases than
      controls. We found an inverse dose-response of alpha-cryptoxanthin, total
      tocopherol, and alpha-tocopherol to the odds ratios for cervical SIL after
      adjustment for HPV and other confounders. The odds ratio among women in the
      highest compared with the lowest quartile was 0.3 (95% confidence interval, 0.1
      0.7) for alpha-cryptoxanthin and 0.3 (95% confidence interval, 0.1-0.8) for alpha
      tocopherol. Negative trends in the odds ratios were suggested for other
      carotenoids and vitamin C, but these were weak, and confidence intervals were
      wide. Our results support existing evidence that high plasma levels of
      antioxidants may reduce the risk of cervical SILs independent of HPV infection.
      These findings are significant because diet is potentially modifiable, and
      nutrition education and dietary intervention might be targeted at specific high
      risk groups.

PMID- 9641500
TI  - Biomonitoring of United States Army soldiers serving in Kuwait in 1991.
AB  - Biomarkers of polycyclic aromatic hydrocarbon (PAH) exposure and genetic
      biomarkers of potential cancer susceptibility were determined in a group of
      United States Army soldiers who were deployed to Kuwait and Saudi Arabia in 1991
      in the aftermath of the Persian Gulf War. Because hundreds of oil well fires were
      still burning, there was concern that ground troops stationed in Kuwait might be
      exposed to high levels of PAHs and other toxicants. The United States Army
      Environmental Hygiene Agency monitored air and soil for ambient PAHs. In
      addition, a group of 61 soldiers was involved in the biomonitoring study reported
      here. These soldiers kept diaries of daily activities and provided blood and
      urine samples in Germany (June) before deployment to Kuwait, after 8 weeks in
      Kuwait (August), and 1 month after the return to Germany (October). Here we
      present data for PAH-DNA adducts measured by immunoassay in blood cell DNA
      samples obtained at all three sampling times from 22 soldiers and bulky aromatic
      adducts measured by 32P-postlabeling in blood cell DNA samples from 20 of the
      same soldiers. Urinary 1-hydroxypyrene-glucuronide levels were determined by
      synchronous fluorescence spectrometry in a matched set of samples from 33
      soldiers. Contrary to expectations, environmental monitoring showed low ambient
      PAH levels in the areas where these soldiers were working in Kuwait. For both DNA
      adduct assays, levels were the lowest in Kuwait in August and increased
      significantly after the soldiers returned to Germany (October). Urinary 1
      hydroxypyrene-glucuronide levels were also lowest in Kuwait and highest in
      Germany, but the differences were not statistically significant. The PAH-exposure
      biomarker levels were not significantly influenced by polymorphic variations of
      CYP1A1 (MspI) and glutathione S-transferases M1 and T1. Overall, the data suggest
      that this group of soldiers was not exposed to elevated levels of PAHs while
      deployed in Kuwait.

PMID- 9641501
TI  - Genetic polymorphisms in glutathione S-transferase mu and theta, N
      acetyltransferase, and CYP1A1 and risk of gliomas.
AB  - The role of genetic polymorphisms in modulating susceptibility to carcinogenic
      exposures has been well explored for tobacco-related neoplasms but not for other
      neoplasms including gliomas. It is relevant to explore these polymorphisms
      because certain carcinogenic exposures such as nitrosamines are implicated in the
      risk of gliomas. We therefore conducted a pilot case-control study to examine the
      role of polymorphisms in GSTM1, GSTT1, NAT2 (rapid, intermediate, and slow
      acetylation), and CYP1A1 and risk of glioma. Ninety patients diagnosed with
      glioma were ascertained as part of an ongoing genetic epidemiological study and
      were age, gender, and race matched with 90 healthy controls. We used PCR based
      methodology to determine the prevalence of the above genetic polymorphisms using
      sequences and PCR conditions directly adapted from studies reported previously.
      We calculated univariate odds ratios and performed multiple logistic regression
      to assess interactions between polymorphisms. We found no statistically
      significant associations between the null genotypes of GSTM1 and GSTT1, and
      CYP1A1 and risk of gliomas. However, there was an intriguing pattern with NAT2
      acetylation status (odds ratios, 1.81, 1.34, and 0.61 for rapid, intermediate,
      and slow acetylation, respectively; P = 0.10 for trend). It is unlikely that any
      single polymorphism is sufficiently predictive of risk, and a panel of markers
      integrated with epidemiological data should be conducted on a large number of
      study subjects to fully understand the role of genetic polymorphisms and brain
      tumor risk.

PMID- 9641502
TI  - A randomised double-blind 16-week study of ritanserin in fibromyalgia syndrome:
      clinical outcome and analysis of autoantibodies to serotonin, gangliosides and
      phospholipids.
AB  - The aim of the study was to evaluate in a double-blind manner the effect of the
      long-acting 5-hydroxytryptamine 2 (5-HT2)-receptor blocker Ritanserin on clinical
      symptoms in patients with fibromyalgia syndrome (FM) and on production of
      antibodies to serotonin, gangliosides and phospholipids, recently shown to have a
      high incidence in this disease. Fifty-one female patients with typical FM were
      included in the 16-week study: 24 received Ritanserin and 27 received a placebo.
      Antibodies to 5-HT, gangliosides (Gm1) and phospholipids (thromboplastin) were
      determined by enzyme-linked immunosorbent assay at day 0 and at the end of week
      16. The psychological and physical status, including tender points, of the
      patients was evaluated at day 0 and at the end of weeks 4 and 16. At the end of
      the study, there was an improvement (p < 0.05) in feeling refreshed in the
      morning in the Ritanserin-treated group and headache was also significantly
      improved compared with the placebo group. There was no difference in pain,
      fatigue, sleep, morning stiffness, anxiety and tender point counts in the
      Ritanserin and placebo groups. Fifty-one per cent of the 51 patients had at least
      one of the three antibodies to 5-HT, Gm1 and phospholipids. The incidence and
      activity of these antibodies were not influenced by Ritanserin or placebo. The
      observation that Ritanserin has only a small effect on clinical symptoms
      indicates that disturbances in serotonin metabolism or uptake may be only one
      factor in the pathogenesis of the disease. The high incidence of a defined
      autoantibody pattern in FM could again be confirmed in this study. However, it
      remains speculative whether immunological reactions are, indeed, involved.

PMID- 9641503
TI  - Osteonecrosis of the tibial plateau.
AB  - The clinical, radiographic and scintigraphic findings in 12 patients diagnosed
      with osteonecrosis of the tibial plateau (10 of the medial and two of the lateral
      plateau) were analysed. The disease presented suddenly in most of the patients,
      as acute pain in the lateral side of the knee, with no major traumatic
      antecedents. X-ray findings were varied and non-specific, and hence of little
      value for initial diagnosis. On the other hand, scintigraphic findings were very
      useful for diagnostic purposes in all cases. All the patients were over 55 years
      of age and 11 out of 12 were women. The most frequent location of the disease was
      the medial tibial plateau; however, two cases involved the lateral plateau and
      two involved both plateaux. Seven patients were subjected to full knee
      arthroplasty, four to valgising osteotomy and one to grafting. The patients'
      diagnoses were considerably delayed (by more than 6 months), which affected their
      treatment and prognosis.

PMID- 9641504
TI  - Chondrocyte phenotyping in human osteoarthritis.
AB  - Cell-ECM (extracellular matrix) interactions are believed to play a key role in
      maintaining the normal structure of tissues such as cartilage. Cell surface
      adhesion molecules have been reported to mediate chondrocyte binding to ECM
      proteins in human normal cartilage but the behaviour of these molecules in human
      osteoarthritic cartilage is unknown. We studied receptor matrix proteins on
      freshly isolated chondrocytes obtained from 10 patients with osteoarthritis (OA).
      Chondrocytes were isolated by enzymatic digestion from three zones of the
      articular cartilage with a different degree of macroscopic and microscopic damage
      and chondrocyte phenotype was defined by flow cytometry. Chondrocytes strongly
      expressed beta1, integrin but not beta3 integrin. LFA-1 (CD18/CD11a) and ICAM-1
      (CD54) antigens were almost undetectable. Interestingly, beta1 expression was
      significantly higher in the minimally damaged zone than in the zones with medium
      and maximum damage. These data show that beta1-integrin-mediated chondrocyte-ECM
      interactions decrease in osteoarthritic cartilage suggesting that perturbations
      of chondrocyte-matrix signalling occurs during OA.

PMID- 9641505
TI  - HLA-DR gene frequencies in a Zairean population with particular reference to
      rheumatic diseases.
AB  - Epidemiological studies have shown that rheumatic diseases such as rheumatoid
      arthritis and systemic lupus erythematosus are uncommon in black Africans, and in
      this population the prevalence and the clinical features of these rheumatic
      diseases are variable. Environmental and genetic factors have been pointed out to
      explain this variability. In the present study, HLA-DR genes have been determined
      in a Zairean population in order to compare our results with those found
      elsewhere in other black populations of the same Bantu origin. Our results show
      that the frequency of HLA-DR1 is higher than in Nigerians, Zimbabweans and
      Xhosas, the decrease in Xhosas being statistically significant (p < 0.006). The
      HLA-DR3 frequency is higher in Zaireans than in Nigerians but not significantly,
      while it is lower than in Xhosas (p < 0.003) and in Zimbabweans (not
      significant). The HLA-DR4 frequency is higher in Zaireans than in Nigerians but
      it is lower than in Xhosas and Zimbabweans; the differences are not statistically
      significant. The HLA-DR8 frequency is lower in Zaireans than in Nigerians while
      it is higher than in Xhosas (p < 0.002) and in Zimbabweans (not significant).
      These data suggest that genetic factors partly explain the clinical and
      epidemiological variability of rheumatic diseases in black Africans.

PMID- 9641506
TI  - Prolactin and interleukin-6 in neuropsychiatric lupus erythematosus.
AB  - We investigated the levels of prolactin (PRL) and interleukin-6 (IL-6) in the
      cerebrospinal fluid (CSF) and serum of systemic lupus erythematosus patients with
      central nervous system involvement (CNS-SLE), and examined whether PRL and IL-6
      have a relationship. Serum and CSF PRL and IL-6 were measured in the following
      groups of patients and controls: group I: seven patients with CNS-SLE; group II:
      three SLE patients without CNS involvement (non CNS-SLE); group III: 10 patients
      with neurocysticercosis; and group IV: six healthy women. The patients were
      clinically assessed. CSF PRL and IL-6 were elevated in group I (CNS-SLE) in
      comparison with all other groups (p<0.001). In addition, four of seven patients
      had higher levels of IL-6 and PRL in CSF than in serum. A positive correlation
      between PRL and IL-6 in CSF of SLE was observed (r=0.88, p<0.001). The mean serum
      PRL concentrations were not significantly different in all groups, but high
      levels of IL-6 were found in the serum of group I in comparison with groups II
      and IV (p<0.001). The serum levels of group III were not different from those of
      group I. These results demonstrate the presence of intrathecal synthesis and
      elevations of CSF PRL and IL-6 in active CNS-SLE involvement and indicate that
      measurements of CSF PRL and IL-6 may be useful in the evaluation of
      neuropsychiatric lupus erythematosus.

PMID- 9641507
TI  - Systemic sclerosis stimulates angiogenesis in the chick embryo chorioallantoic
      membrane.
AB  - Skin biopsies from patients with systemic sclerosis (SSc) were investigated for
      their angiogenic activity by using the chick embryo chorioallantoic membrane
      (CAM) assay. Ten samples of SSc and 10 of normal skin from age- and sex-matched
      subjects were grafted onto the CAM, and the angiogenic response in pathological
      and control implants was assessed on histological sections by a planimetric point
      count method 4 days after grafting. The vascular counts in the area underlying
      the SSc were significantly higher than those of normal skin and a dense
      mononuclear cell infiltrate was detectable around the blood vessels in
      pathological specimens. These results suggest that SSc may promote angiogenesis,
      perhaps leading to the release of several angiogenic factors. Moreover, the role
      played in the angiogenic response by the inflammatory cells forming the cellular
      infiltrate is suggested by this study.

PMID- 9641508
TI  - HLA B27: a prognostic factor in juvenile chronic arthritis.
AB  - This study was performed to assess the frequency of HLA B27 in patients with
      juvenile chronic arthritis (JCA) of varying severity and outcome by studying
      three patient categories: those in whom cytostatic treatment with azathioprine
      had been started, those with secondary amyloidosis, and those with arthroplasty
      of the knee or hip joints. In the first category the frequency of the HLA B27
      allele was compared between those who had attained remission and those who had
      not. In the second and third categories the rate at which amyloidosis developed
      and the timing for the need of arthroplasty, were compared for HLA B27-positive
      and -negative patients. A control group consisted of 37 patients with
      uncomplicated seronegative polyarthritis. Ten of the 37 patients in the control
      group (27%) were HLA B27 positive as opposed to 84 out of 190 (44%) in the three
      study groups. Of the 101 patients treated with azathioprine, two out of 15 in
      remission were HLA B27 positive, whereas as many as 41 out of 86 with still
      active disease were HLA B27 positive (p = 0.013). Of the secondary amyloidosis
      patients, 29 out of 51 carried HLA B27. The HLA B27-positive patients contracted
      amyloidosis on average 5.9 (median 6.7) years earlier than the HLA B27-negative
      patients (p = 0.038). Of the arthroplasty patients, 39 out of 91 carried HLA B27.
      The HLA B27-positive patients underwent arthroplasty on average 2.9 (median 3.5)
      years earlier than the HLA B27-negative patients (p = 0.050). We conclude that
      HLA B27-positive cases are accumulated among the most severe cases of JCA.

PMID- 9641509
TI  - A self-report Thompson articular index: what does it measure?
AB  - The aim of this study was to investigate the reliability and validity of the self
      report Thompson articular index (ThAI) in Dutch patients with rheumatoid
      arthritis (RA). A rheumatologist assessed the ThAI in 43 patients with RA.
      Patients completed the self-report ThAI and the AIMS-2 questionnaire to assess
      physical function, pain, mood and level of tension. Blood samples were taken to
      measure the erythrocyte sedimentation rate (ESR). After 4 weeks, patients were
      sent a questionnaire for a repeat assessment of the self-report AI. The test
      retest reliability of the self-report ThAI was adequate (ICC=0.83). There was low
      agreement between ThAI scores from patients and AI scores assessed by the
      rheumatologist (ICC=0.44). Self-report ThAI scores (mean=230.5) were
      significantly higher than the rheumatologist's scores (mean=110.8). Levels of
      agreement between patients and rheumatologist for individual joints were
      disappointing, ranging from 49% to 74% (Cohen's kappa from -0.02 to 0.48). The
      rheumatologist's ThAI scores correlated significantly with ESR (r=0.55) and
      physical function (r=0.44), but not with pain, mood or level of tension.
      Patients' scores correlated significantly with physical function (r=0.51), pain
      (r=0.43), and mood (r=0.36) but not with ESR or level of tension. In regression
      analyses the only significant predictor of the rheumatologist's ThAI scores was
      ESR, and for patients' scores physical function, thus showing that patients'
      responses are not confounded by mood or level of tension. In conclusion, the self
      report ThAI is a reliable measure, but the validity is questionable because of
      the non-significant correlation with ESR and the low level of agreement between
      patients and rheumatologist. The results indicate that self-reported joint
      involvement is more closely related to physical function than to arthritic
      activity.

PMID- 9641510
TI  - Outcomes for patients undergoing one or more total hip and knee arthroplasties.
AB  - Either total hip arthroplasty (THA), total knee arthroplasty (TKA) or both were
      performed in 105 patients from 1981 to 1994. These patients were experiencing
      severe joint destruction in the lower extremities due to rheumatoid arthritis
      (RA). These patients were followed for more than 2 years after their last
      operation. Eighty-six patients were alive and 19 patients had died at the time of
      follow-up. The 86 living patients were divided into four groups based on the
      number of replaced joints. Their pre- and postoperative conditions, including
      such factors as pain, mobility and disability for the quality of life (QOL), were
      compared. All of the four groups showed some reduction in pain and disability,
      and an improvement in ambulation after the operations. The 19 deceased patients
      were classified into two groups, one including those with multiple (three or
      four) arthroplasties and the other, those with only a small number (one or two).
      The mean age at death was lower (55.7+/-6.2 years) in patients with multiple
      arthroplasties than that (69.1+/-7.5 years) in patients with only a small number
      of arthroplasties. Secondary diseases from RA, such as amyloidosis, spinal injury
      and pulmonary fibrosis, were found to be the primary cause of death in patients
      with multiple arthroplasties. The most important finding in this study is that
      although RA patients with multiple arthroplasties in the lower extremities
      improved their QOL, they were still afflicted with secondary diseases derived
      from RA and experienced complications that could shorten their lifespan.

PMID- 9641511
TI  - When does subluxation of the first carpometacarpal joint cause swan-neck
      deformity of the thumb in rheumatoid arthritis: a 20-year follow-up study.
AB  - The aim of our study was to assess the incidence of subluxation of the first
      carpometacarpal joint (CMC I) and to evaluate which degree of subluxation
      produces swan-neck deformity of the thumb in rheumatoid arthritis (RA) occurring
      over 20 years. The hands of 83 rheumatoid factor (RF)-positive RA patients with
      recent (< or = 6 months) arthritis were evaluated radiographically at onset and
      at 1, 3, 8 and 15 years; 68 patients were evaluated at 20 years from entry.
      Subluxation was assessed in millimetres and compared with the MCP-I angle
      measurement to evaluate the thumb deformity. A statistical end-point analysis was
      performed between two different grades of subluxation. Subluxation of 2-3 mm was
      non-specific and only one third of these thumbs showed swan-neck deformity. At
      the end-point, subluxation of > or = 4mm was present in 17% of the thumbs, 81% of
      which had the swan-neck deformity; only five thumbs did not show this deformity,
      but presented deformed and unstable MCP I and interphalangeal joints. The
      frequency of swan-neck deformity was highly significantly (p < 0.0001) increased
      in the thumbs with severe CMC I subluxation (> or = 4 mm) compared with lesser
      subluxation (< 4 mm). When subluxation of the CMC I exceeds 4 mm, the swan-neck
      deformity of the thumb is a common consequence. This deformity is often
      progressive, and the hand function of such patients should be followed up
      carefully, both clinically and radiographically.

PMID- 9641512
TI  - Does the French general practitioner correctly investigate and treat
      osteoporosis? Groupe Rhumatologique d'Etudes Cliniques de Midi-Pyrenees.
AB  - In our region, more than half the patients with osteoporosis are investigated and
      treated by general practitioners. We carried out two surveys to discover whether
      the diagnosis and treatment of osteoporosis were correctly carried out by general
      practitioners in the Midi-Pyrenees region. The first survey concerned 85 patients
      who had been diagnosed with osteoporosis by their general practitioner. These
      patients were being seen for the first time in a hospital or private practice
      setting by a rheumatologist who completed a questionnaire based solely on the
      history taken from the patient and the records in the patient's possession. For
      the second survey, 200 general practitioners who had referred patients to the
      rheumatology department were sent a questionnaire on their management of
      osteoporosis. Fifty-two physicians completed and returned the questionnaire. More
      than half the general practitioners started treatment of osteoporosis without
      fractures on the basis of standard spinal X-rays where the radiologist suggested
      bone mineral loss. The initial biological investigation was correctly carried out
      by only 6% of physicians. Treatment was correctly prescribed in only 34% of cases
      of osteoporosis with fractures, 50% of osteoporosis without fractures and 50% of
      senile cortical osteoporosis.

PMID- 9641513
TI  - Anti-transfer RNA antibodies in two patients with pulmonary fibrosis, Raynaud's
      phenomenon and polyarthritis.
AB  - Patient W.S. (a 61-year-old woman) and patient T.M. (a 41-year-old man) developed
      recurrent fevers, polyarthritis, Raynaud's phenomenon and interstitial pulmonary
      fibrosis without apparent polymyositis. From HeLa cell extracts, sera from both
      patients immunoprecipitated all species of intact and deproteinised tRNAs. To
      identify the antibody binding site more precisely, tRNAs transcribed in vitro
      from cloned Escherichia coli tRNA genes and various mutants were prepared and
      used as antigens for immunoprecipitation. When the TpsiC loop, or the D loop were
      deleted, such mutants were not bound by both sera, suggesting that the D and
      TpsiC loops were required for antibody binding. Abrogation of tRNA binding
      occurred when 18G of tRNATrp was replaced with 18A to break the tertiary L-shape
      structure of tRNA. These results strongly suggest that sera from W.S. and T.M.
      recognise the tertiary conformation of L-shaped tRNA which is constructed with
      both D and TpsiC loops. These autoantibodies may also serve as a marker for a new
      subset of patients with connective tissue diseases that is distinct from anti
      aminoacyl-tRNA synthetase syndrome.

PMID- 9641514
TI  - Polyarthritis, rash and lymphadenopathy: case reports of two patients with
      angioimmunoblastic lymphadenopathy presenting to a rheumatology clinic.
AB  - Two patients presented with a symmetrical inflammatory polyarthropathy. Both
      patients fulfilled the diagnostic criteria for angioimmunoblastic
      lymphadenopathy. We present the two case histories and review the current
      literature. Although an uncommon disease, the diagnosis of angioimmunoblastic
      lymphadenopathy should be considered in a patient presenting with polyarthritis
      and skin rash.

PMID- 9641515
TI  - Tenosynovitis due to Mycobacterium avium intracellulare and Mycobacterium
      chelonei: report of two cases with review of the literature.
AB  - Atypical mycobacteria can induce soft tissue infections such as tenosynovitis. We
      observed one case of finger flexor tendon tenosynovitis infected with
      Mycobacterium avium intracellulare and one case of knee and ankle arthritis with
      lateral peroneal tendon tenosynovitis due to M. chelonei. In the first patient, a
      tenosynovectomy only was performed leading to resolution of the infection. The
      second patient was immunocompromised as a result of corticosteroid therapy and
      the mycobacterial infection was treated with tenosynovectomy and multidrug
      chemotherapy. This patient died from infectious pneumonitis. Previously reported
      cases of infectious tenosynovitis due to these atypical mycobacteria are
      reviewed.

PMID- 9641516
TI  - Flexion contractures associated with a malignant neoplasm: 'A paraneoplastic
      syndrome?'.
AB  - A 71-year-old man developed polyarthritis and, subsequently, severe flexion
      contractures of multiple joints, particularly the joints of the hands. Eighteen
      months after developing this disease a parailiacal lymph node metastasis of an
      unknown primary cancer was found. We suggest that this patient's history,
      dominated by contractures that resembled the 'palmar fasciitis and polyarthritis
      syndrome', should be considered as a paraneoplastic syndrome.

PMID- 9641517
TI  - Very low-dose cyclosporin treatment of steroid-resistant interstitial pneumonitis
      associated with Sjogren's syndrome.
AB  - Cyclosporin is known to be effective for both transplantation and a spectrum of
      immune-mediated diseases. Because this agent also causes severe adverse effects,
      especially nephrotoxicity, careful monitoring is required for the development of
      such reactions. Here we report the successful treatment with extremely low-dose
      cyclosporin (1 mg/kg/day) of a patient who had steroid-resistant interstitial
      pneumonitis and Sjogren's syndrome.

PMID- 9641518
TI  - Peripheral neuropathy associated with temporal arteritis.
AB  - Peripheral neuropathy is described in a patient with biopsy proven giant cell
      arteritis. Sural nerve biopsy showed myelin and axonal degeneration. Such an
      uncommon manifestation was resolved with corticosteroid therapy.

PMID- 9641519
TI  - Granulomatous tenosynovitis: a rare musculoskeletal manifestation of
      tuberculosis.
AB  - A patient with tenosynovial tuberculosis affecting the extensor tendons of the
      wrist and hand is presented. This case highlights the clinical and magnetic
      resonance features of tuberculous tenosynovitis, and seeks to increase awareness
      of what may represent a resurgent musculoskeletal entity.

PMID- 9641520
TI  - Rotator cuff tear associated with an acromioclavicular cyst in rheumatoid
      arthritis.
AB  - We report two cases of a full-thickness rotator cuff tear followed by
      acromioclavicular cyst formation in patients with longstanding erosive
      polyarticular rheumatoid arthritis. One of the consequences of a rotator cuff
      tear is articular instability with upward migration of the humeral head. The
      ensuing chronic friction against the undersurface of the acromioclavicular joint
      caused by arm movements can lead to a non-inflammatory effusion of the
      acromioclavicular joint with cyst formation. Clinical and ultrasonographic
      features and a pathogenetic hypothesis are discussed.

PMID- 9641521
TI  - Buschke-Ollendorff syndrome in a grande multipara: a case report and short review
      of the literature.
AB  - A 36-year-old short-statured grande multipara (gravida 10, para 8) with diabetes
      mellitus and hyperlipidaemia was incidentally found to have Buschke-Ollendorff
      syndrome (osteopoikilosis and dermatofibrosis lenticularis disseminata). The
      pelvis and hips, followed by the knees, were the sites mainly affected by the
      osteopoikilosis. The lumbosacral spine was also affected. She had a single
      connective tissue naevus on the right thigh. Apart from two abortions, the
      repeated pregnancies were uneventful and all her deliveries were normal at full
      term or nearly full-term. With regard to the relationship between Buschke
      Ollendorff syndrome and multiparity, it was apparent that multiparity did not
      affect the involved weight bearing bony structures, nor did the disseminated
      osteopoikilosis interfere with the endurance of multiple pregnancies. Buschke
      Ollendorff syndrome is known generally to have a benign course, a feature that is
      illustrated in this case, even when associated with the stresses of multiparity.
      The report also provides a short and updated review of various clinical aspects
      of the syndrome and its associations, some of which are of a serious nature.

PMID- 9641522
TI  - Superior vena cava syndrome together with multiple venous thrombosis in Behcet's
      disease.
AB  - In this paper, we describe a 25-year-old white man with Behcet's disease who
      developed superior vena cava syndrome which was followed with the diagnosis of
      pseudotumour cerebri based on bilateral papilledema for 6 months. Complete
      superior vena cava obstruction was detected by magnetic resonance imaging (MRI).
      Secondary reasons for papilledema were all excluded. Treatment of prednisone,
      pulse cyclophosphamide and heparin was started and clinical symptoms and
      fundoscopic changes completely disappeared in 2 weeks. In conclusion, we think
      that Behcet's disease should always be remembered in the differential diagnosis
      of unidentified neurological signs especially in regions where the disease is
      relatively common.

PMID- 9641523
TI  - Amino acid transport in cerebral microvessels during Plasmodium yoelii infection
      in mice.
AB  - Plasmodium yoelii infected cerebral microvessels of mice had an enhanced time
      dependent, temperature-sensitive, and saturable uptake of [14C]-amino acid. viz.
      leucine, valine and glycine. Metabolic inhibitors caused a noticeable inhibition
      of amino acid uptake in normal microvessels as compared to infected cerebral
      microvessels indicating that the uptake of [14C]-L-leucine, [14C]-L-valine and
      [14C]-glycine is an energy dependent process.

PMID- 9641524
TI  - Developmental expression of nitric oxide synthase in the rat diencephalon with
      special reference to the thalamic paratenial nucleus.
AB  - Using immunohistochemistry and in situ hybridization the distribution of nitric
      oxide synthase (NOS) was investigated in the rat brain during pre- and postnatal
      development. At E15 weak NOS-like immunoreactivity (NOS-LI) could be seen in the
      differentiation field of the anterior hypothalamus. At E17 strong NOS-LI was
      observed in the developing neurons of the hypothalamic paraventricular nucleus,
      supraoptic nucleus, anterodorsal nucleus and lateral hypothalamic areas. In the
      thalamic paratenial nucleus a strong NOS-LI was observed in these neurons at E17,
      E18 and P1 with a weaker intensity at P3, P7, P9 and P15, whereas at P30 and in
      adult rats no NOS-positive neurons could be detected. NOS expression at E17 and
      P3 was verified by in situ hybridization. These results suggest that NO may have
      a developmental role at least in one of the regions studied, the thalamic
      paratenial nucleus.

PMID- 9641526
TI  - Expression of GABA(A) receptors by reactive astrocytes in explant and primary
      cultures of rat CNS.
AB  - The presence of GABA(A)-receptors on astrocytes was studied in explant and
      primary cultures of rat cerebellum, hippocampus and spinal cord by means of
      immunohistochemistry. For these studies we have used the monoclonal antibody bd
      17 against the beta2- and beta3-subunits of GABA(A)-receptor. In explant cultures
      many neurones were intensely stained with the GABA(A)-receptor antibody whereas
      adjacent astrocytes revealed little or no immunoreactivity. In the far outgrowth
      zone of explant culture, however, many immunostained astrocytes were observed. In
      primary astrocyte cultures, only a few cells were stained by the antibody.
      Astrocytes which became reactive after producing an artificial scar or after
      addition of certain compounds such as dibutyryl cyclic AMP, interleukin-6, basic
      fibroblast growth factor and kainic acid, also revealed GABA(A)-receptor
      immunoreactivity. Furthermore, these astrocytes were intensely stained for glial
      fibrillary acidic protein and vimentin. From our studies we conclude that only a
      sub-population of normal astrocytes are immunopositive for the GABA(A)-receptor
      antibody whereas astrocytes which become reactive following injury of the tissue
      or after addition of dibutyryl cyclic AMP, the cytokine interleukin-6, fibroblast
      growth factor or the neurotoxin kainic acid express GABA(A)-sites.

PMID- 9641525
TI  - Alterations in the activities of cerebral antioxidant enzymes of rat are related
      to aging.
AB  - Developmental profiles of antioxidant enzymes and lipid peroxidation were
      investigated in rat cerebral hemisphere from birth to 600 days of age. Lipid
      peroxidation level decreased in the crude homogenate from birth until 15 days
      and, thereafter increased gradually up to 600 days. However, susceptibility of
      sub-cellular fractions to lipid peroxidation displayed an increasing trend with
      increasing age. Superoxide dismutase activity decreased gradually with age,
      whereas activities of catalase, glutathione peroxidase and glutathione reductase
      exhibited an elevation up to 90 days followed by either a stagnancy or diminution
      in the later life. No linearity was observed in the contents of glutathione,
      ascorbic acid and H2O2 in the tissue. The results suggest that free radicals
      could be the causative agents of the aging process in which antioxidant enzymes
      have a definite regulatory contribution.

PMID- 9641527
TI  - Effects of oxidative stress on prion protein expression in PC12 cells.
AB  - PC12 cells are known to express the prion protein, a normal cell surface
      glycoprotein. This protein is upregulated in PC12 cells differentiated with nerve
      growth factor. A neurotoxic prion protein peptide, PrP106-126, is not toxic to
      PC12 cells alone. PrP106-126 is toxic to PC12 cells co-cultured with microglia
      and more so to NGF-differentiated PC12 cells. PC12 cells selected for resistance
      to either copper toxicity or oxidative stress have higher levels of PrP(C)
      expression. Both PC12 variants are more sensitive to the toxicity of PrP106-126.
      This suggests that PC12 sensitivity to PrP106-126 toxicity is related to prion
      protein expression and not to a state of high differentiation induced by NGF.
      Variants of PC12 cells that are more resistant to copper toxicity have higher
      levels of anti-oxidant enzymes, superoxide dismutase and glutathione peroxidase.
      Our results suggest that cells expressing higher levels of PrP(C) have higher
      resistance to oxidative stress or copper toxicity but are more sensitive to
      PrP106-126 toxicity. Prion protein expression may be involved in both the
      metabolism of copper and resistance to oxidative stress. Increased cellular
      resistance to copper toxicity may be partly related to increased activity of anti
      oxidant enzymes.

PMID- 9641528
TI  - The effects of TGF-beta1 on chick embryo retina development in vitro.
AB  - This paper studies the effect exerted by TGF-beta1 on the development of chick
      embryo retina cultured in vitro. The addition of TGF-beta1 to retinal explants
      inhibited DNA synthesis, measured as 3H-thymidine incorporation into
      trichloroacetic acid-insoluble fraction, while it increased both wet weight and
      protein content, in particular that of extracellular matrix proteins. Lastly, in
      explants treated with TGF-beta1 an increment in the level of fibronectin was
      demonstrated by means of Western blotting analysis.

PMID- 9641529
TI  - Brain-derived neurotrophic factor gene expression in the developing zebrafish.
AB  - Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family
      of polypeptides that includes NGF, NT-3, NT-4/5 and NT-6. Although neurotrophins
      are known to be expressed in teleost fishes little is known about their functions
      in the development of these vertebrates. We are therefore studying BDNF in the
      zebrafish, Danio rerio. The structure of zebrafish BDNF mRNA was established
      using PCR and cDNA cloning. The encoded BDNF was 91% identical to mammalian BDNF.
      Southern blot analysis revealed a unique BDNF gene. Northern blot analysis
      detected two heterogeneous populations of BDNF transcripts centered at 1.6 and 2
      kb. BDNF transcripts were first measurable 24 h post-fertilization (pf). Their
      abundance relative to total transcripts increased 6-fold between 1 day and 3 days
      pf and again 2-fold by 7 days pf. In situ hybridization analyses of 4-day-old
      larvae revealed BDNF transcripts in the retina, brain, otic vesicle, pectoral fin
      and the hair cells of the neuromast. The early onset and cellular sites of
      expression suggest that BDNF functions in nervous system and fin development in
      the zebrafish.

PMID- 9641530
TI  - Visual perception: myths and mechanisms.

PMID- 9641531
TI  - Mathematical guidance for axons.
AB  - Axon guidance by gradients plays an important role in wiring up the developing
      nervous system. Growth cones seem to sense a concentration difference across
      their spatial extent, and convert this into a signal to move up or down a
      gradient. In this article, a simple mathematical framework is developed to
      understand when and where gradient detection can occur as a function of gradient
      shape. This framework is applied to two examples:the guidance of axons by target
      derived diffusible factors in vivo and in collagen gels, and guidance by
      substrate-bound gradients of optimal shape, as might be relevant in the
      retinotectal system.Two distinct spatial limits on guidance emerge: I mm for a
      target-derived diffusible gradient, and I cm for a substrate-bound gradient.

PMID- 9641532
TI  - Simulation in neurobiology: theory or experiment?
AB  - Investigation in neurophysiology usually involves measurements of large
      population-average signals or small sample recordings. There is an underlying
      assumption that the observations express activity of large groups of similarly
      acting neurons that is the result of a bottom-up scenario in which individual
      cells, via their synaptic interactions, lead to the large scale phenomena. The
      connection between the levels must be provided by theory, which must also provide
      the relevant variables for observation. It is suggested that between the
      experiment and the full theory there is a creative, mixed role for simulation:
      both experimental and theoretical. A simulation presents complex dynamics and
      hence is an empirical board for testing theoretical tools, yet its controlled
      behaviour can make predictions about the biological system.

PMID- 9641533
TI  - Rembrandt's 'The anatomy lesson of Dr. Joan Deijman'.
AB  - Rembrandt's striking painting of a human brain being dissected by a headless
      figure is actually a fragment of a larger work. The original was both a
      commissioned group portrait of a surgeons' guild and an account of a public
      dissection. Such dissections served both educational and entertainment functions
      in 17th century Holland.

PMID- 9641534
TI  - Intrinsic circuitry of the amygdaloid complex: common principles of organization
      in rats and cats.

PMID- 9641535
TI  - The GluR2 (GluRB) hypothesis in ischemia: missing links.

PMID- 9641536
TI  - New insights into the regulation and function of brain estrogen synthase
      (aromatase).
AB  - In the brain, conversion of androgens into estrogens by the enzyme aromatase
      (estrogen synthase) is a key mechanism by which testosterone regulates many
      physiological and behavioral processes, including the activation of male sexual
      behavior, brain sexual differentiation and negative feedback effects of steroid
      hormones on gonadotropin secretion. Studies on the distribution and regulation of
      brain aromatase have led to a new perspective on the control and function of this
      enzyme. A growing body of evidence indicates that the estrogen regulation of
      aromatase is, at least in part, trans-synaptic. Afferent catecholamine pathways
      appear to regulate aromatase activity in some brain areas and thereby provide a
      way for environmental cues to modulate this enzyme. The localization of aromatase
      in pre-synaptic boutons suggests possible roles for estrogens at the synapse.

PMID- 9641537
TI  - The synucleins: a family of proteins involved in synaptic function, plasticity,
      neurodegeneration and disease.
AB  - Synuclein proteins are produced, in vertebrates, by three genes. They share
      structural resemblance to apolipoproteins, but are abundant in the neuronal
      cytosol and present in enriched amounts at presynaptic terminals. Synucleins have
      been specifically implicated in three diseases:Alzheimer's (AD), Parkinson's (PD)
      and breast cancer. In AD, a peptide derived from alpha-synuclein forms an
      intrinsic component of plaque amyloid. In PD, an alpha-synuclein allele is
      genetically linked to several independent familial cases, and the protein appears
      to accumulate in Lewy bodies. In breast cancer, increased expression of gamma
      synuclein correlates with disease progression. In songbirds, alpha-synuclein
      expression is correlated with plasticity in the developing song control system.
      Although the normal function of synucleins is unknown, a role in membrane
      plasticity seems likely.

PMID- 9641538
TI  - Is there a vestibular cortex?
AB  - Very different areas of the primate cortex have been labelled as 'vestibular'.
      However, no clear concept has emerged as to where and how the vestibular
      information is processed in the cerebral cortex. On the basis of data from single
      unit recordings and tracer studies, the present article gives statistical
      evidence of the existence of a well-defined vestibular cortical system. Because
      the data presented here have been verified in three different primate species, it
      can be predicted that a similar vestibular cortical system also exists in humans.

PMID- 9641539
TI  - The 'Ideal Homunculus': decoding neural population signals.
AB  - Information processing in the nervous system involves the activity of large
      populations of neurons. It is possible, however, to interpret the activity of
      relatively small numbers of cells in terms of meaningful aspects of the
      environment. 'Bayesian inference' provides a systematic and effective method of
      combining information from multiple cells to accomplish this. It is not a model
      of a neural mechanism (neither are alternative methods, such as the population
      vector approach) but a tool for analysing neural signals. It does not require
      difficult assumptions about the nature of the dimensions underlying cell
      selectivity, about the distribution and tuning of cell responses or about the way
      in which information is transmitted and processed. It can be applied to any
      parameter of neural activity (for example, firing rate or temporal pattern). In
      this review, we demonstrate the power of Bayesian analysis using examples of
      visual responses of neurons in primary visual and temporal cortices. We show that
      interaction between correlation in mean responses to different stimuli (signal)
      and correlation in response variability within stimuli (noise) can lead to marked
      improvement of stimulus discrimination using population responses.

PMID- 9641540
TI  - Development of whisker-related patterns in marsupials: factors controlling
      timing.
AB  - In mature rodents, whisker-related patterns are known to be present in three
      levels of the brain: the brainstem trigeminal nuclei, the ventrobasal thalamus
      and the somatosensory cortex. These patterns have been demonstrated using
      neuroanatomical tracing techniques, histological and histochemical staining
      methods and electrophysiological recordings. The development and topography of
      these patterns are dependent on an intact periphery. But what governs when
      patterns form at the three levels? Possibilities include a controlling signal
      from the periphery or local mechanisms at each site, such as the arrival of
      afferent inputs or the maturation of target tissue. In this review, we report on
      the maturation of the whisker pathway in a marsupial, the wallaby, where the slow
      tempo of development is a feature. At each level, afferent fibres grow into the
      region of termination many weeks before the whisker-related pattern emerges. The
      results suggest that the maturity of the target tissue as well as signals from
      the periphery combine to trigger pattern formation at each level of the pathway.

PMID- 9641541
TI  - Bladder distension and activation of the efferent function of sensory fibres:
      similarities with the effect of capsaicin.
AB  - 1. The effects of the tachykinin NK2 receptor antagonist MEN 11420 (100 nmol kg(
      1), i.v.) and isoprenaline (400 nmol kg(-1), i.v.) were compared in a model of
      distension-induced bladder activity in isovolumetric conditions. MEN 11420
      induced a relaxation of the basal tone of the urinary bladder that was dependent
      on the volume of the viscus: the effect was absent at low volumes (0.2 and 0.5
      ml) and it was maximal at high volumes of distension (1 and 2 ml), approaching
      about 60% of the isoprenaline-induced relaxation. The relaxant effect of
      isoprenaline was always evident at all volumes of distension. 2. Tetrodotoxin (1
      100 microM, intravesically applied) abolished distension-evoked micturition
      contractions, but did not prevent the relaxant effect of MEN 11420- or
      isoprenaline on the bladder tone. 3. The cyclo-oxygenase inhibitor S-ketoprofen
      (0.5 micromol kg(-1), i.v.) produced a marked decrease of the bladder tone and a
      concomitant reduction of bladder motility at 1 ml volume of distension. At 2 ml
      of distension, S-ketoprofen still decreased the minimal pressure but had no
      significant effect on other parameters of vesical motility. In S-ketoprofen
      pretreated rats, the relaxant effect of MEN 11420 was significant at 2 but not at
      1 ml of distension, and that of isoprenaline was reduced by 50% at both 1 and 2
      ml. 4. Ruthenium red (10 micromol kg(-1), i.v.) had no effect at a low volume of
      distension (0.2 ml) or at highest volume (2 ml) but decreased the basal tone and
      the frequency of bladder contractions at 1 ml of distension. In ruthenium red
      pretreated rats, MEN 11420 failed to decrease bladder tone at 1 ml, whereas at 2
      ml the effect of MEN 11420 was not different from that observed in controls (43
      vs 60% of isoprenaline-induced relaxation, respectively). 5. At both 1 and 2 ml
      of distension, capsaicin pretreatment (164 micromol kg(-1), s.c. 5 days before)
      reduced the frequency of micturition contractions but had no effect on the
      bladder tone. Capsaicin pretreatment prevented the relaxant effect of MEN 11420
      on the bladder tone both at 1 and at 2 ml of distension. 6. It is concluded that
      the release of tachykinins from capsaicin-sensitive afferent nerves induced by
      bladder distension is resistant to tetrodotoxin and to prostaglandin synthesis
      inhibition. Tachykinins modulate the vesical tone by acting through NK2
      receptors.

PMID- 9641542
TI  - Effects of tachykinin NK1 receptor antagonists on vagal hyperreactivity and
      neuronal M2 muscarinic receptor function in antigen challenged guinea-pigs.
AB  - 1. The role of tachykinin NK1 receptors in the recruitment of eosinophils to
      airway nerves, loss of inhibitory neuronal M2 muscarinic receptor function and
      the development of vagal hyperreactivity was tested in antigen-challenged guinea
      pigs. 2. In anaesthetized guinea-pigs, the muscarinic agonist, pilocarpine (1-100
      microg kg(-1), i.v.), inhibited vagally induced bronchoconstriction, in control,
      but not in antigen-challenged guinea-pigs 24 h after antigen challenge. This
      indicates normal function of neuronal M2 muscarinic receptors in controls and
      loss of neuronal M2 receptor function in challenged guinea-pigs. Pretreatment of
      sensitized guinea-pigs with the NK1 receptor antagonists CP99994 (4 mg kg(-1),
      i.p.), SR140333 (1 mg kg(-1), s.c.) or CP96345 (15 mg kg(-1), i.p.) before
      antigen challenge, prevented M2 receptor dysfunction. 3. Neither administration
      of the NK1 antagonists after antigen challenge, nor pretreatment with an NK2
      receptor antagonist, MEN10376 (5 micromol kg(-1), i.p.), before antigen
      challenge, prevented M2 receptor dysfunction. 4. Electrical stimulation of the
      vagus nerves caused a frequency-dependent (2-15 Hz, 10 V, 0.2 ms for 5 s)
      bronchoconstriction that was significantly increased following antigen challenge.
      Pretreatment with the NK1 receptor antagonists CP99994 or SR140333 before
      challenge prevented this increase. 5. Histamine (1-20 nmol kg(-1), i.v.) caused a
      dose-dependent bronchoconstriction, which was vagally mediated, and was
      significantly increased in antigen challenged guinea-pigs compared to controls.
      Pretreatment of sensitized animals with CP99994 before challenge prevented the
      increase in histamine-induced reactivity. 6. Bronchoalveolar lavage and
      histological studies showed that after antigen challenge significant numbers of
      eosinophils accumulated in the airways and around airway nerves. This
      eosinophilia was not altered by pretreatment with the NK1 receptor antagonist
      CP99994. 7. These data indicate that pretreatment of antigen-sensitized guinea
      pigs with NK1, but not with NK2 receptor antagonists before antigen challenge
      prevented the development of hyperreactivity by protecting neuronal M2 receptor
      function. NK1 receptor antagonists do not inhibit eosinophil accumulation around
      airway nerves.

PMID- 9641543
TI  - Effects of pravastatin on cholesterol metabolism of cholesterol-fed heterozygous
      WHHL rabbits.
AB  - 1. We administered the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor
      pravastatin at a daily dose of 1 mg kg(-1) body weight to cholesterol-fed (0.03%)
      heterozygous Watanabe heritable hyperlipidaemic rabbits, an animal model for
      heterozygous familial hypercholesterolaemia. 2. After 12 months of cholesterol
      treatment, immunohistochemistry with the monoclonal antibody 9D9 was used to
      detect hepatic low density lipoprotein (LDL) receptors, which were quantified by
      densitometry. In addition we determined LDL receptor mRNA by competitive reverse
      transcriptase polymerase chain reaction. The cholesterol precursor lathosterol
      and the plant sterol campesterol were analysed by gas-liquid chromatography. 3.
      The drug reduced total plasma cholesterol levels by 51% (P=0.04), when compared
      to the control group. Unexpectedly, hepatic LDL receptor density and mRNA showed
      no significant differences between the groups. Total plasma levels of lathosterol
      and campesterol also revealed no significant differences between the groups, if
      expressed relative to plasma cholesterol. 4. The findings suggest that mechanisms
      other than induced hepatic LDL receptors are responsible for the cholesterol
      lowering effect of pravastatin in this animal model. We propose a reduced
      cholesterol absorption efficiency compatible with similar campesterol levels
      between both groups observed in our study.

PMID- 9641544
TI  - G-protein activation at 5-HT1A receptors by the 5-ht1F ligand LY334370 in guinea
      pig brain sections and recombinant cell lines.
AB  - 1. G-protein activation by the 5-ht1F receptor agonist 5-(4-fluorobenzoyl)amino-3
      (1-methylpiperidin-4-yl)-1H-indole fumarate (LY334370) was investigated by use of
      autoradiography of receptor-activated G-proteins in guinea-pig brain sections and
      [35S]-GTPgammaS binding responses in cell lines stably expressing human 5-HT1A (h
      5-HT1A) receptors. 2. LY334370 (10 microM) caused little or no stimulation of
      [35S]-GTPgammaS binding in guinea-pig brain regions enriched in 5-ht1F binding
      sites (e.g., claustrum, caudate/putamen and thalamic nuclei), as identified by
      labelling with 10 nM [3H]-sumatriptan plus 10 nM 5-carboxamidotryptamine (5-CT).
      3. Application of LY334370 (10 microM) to guinea-pig brain sections resulted in
      an increase of [35S]-GTPgammaS binding in hippocampus (123+/-17%), lateral septum
      (58+/-14%), dorsal raphe (57+/-10%), entorhinal (37+/-11%) and cingulate cortex
      (28+/-10%). This distribution fits with the G-protein activation mediated by 5
      HT1A receptors as found with lisuride (10 microM), and labelling of 5-HT1A
      receptors by 140 pM [125I]-4-(2'-methoxy-phenyl)- -[2'-(n-2"-pyridinyl)-p
      iodobenzamido]-ethyl-piperazine (p-MPPI). 4. The LY334370-mediated [35S]
      GTPgammaS response was antagonized by the selective, silent 5-HT1A receptor
      antagonist N-[2-[4-(2-methoxyphenyl)1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohex
      anecarboxa-mide (WAY100635, 1 microM) in each of the brain structures
      investigated. The distribution pattern of the [35S]-GTPgammaS binding response
      and the antagonist profile suggest that the LY334370-induced response in guinea
      pig brain is mediated by 5-HT1A receptors. 5. The maximal LY334370-induced [35S]
      GTPgammaS binding response (83 to 94%) in membranes of recombinant C6-glial/h 5
      HT1A and HeLa/h 5-HT1A cells was close to that of 5-HT, suggesting LY334370 to
      exert high intrinsic activity at h 5-HT1A receptors. 6. In conclusion, in guinea
      pig brain sections and recombinant cell lines the 5-ht1F receptor agonist
      LY334370 causes G-protein activation that is mediated by 5-HT1A receptors.
      Caution should be taken when employing this ligand as a putative selective 5-ht1F
      agonist.

PMID- 9641545
TI  - Modulation of angiotensin-converting enzyme by nitric oxide.
AB  - 1. The aim of the present study was to determine the effect of nitric oxide (NO)
      on angiotensin-converting enzyme (ACE) activity. 2. A biochemical study was
      performed in order to analyse the effect of the NO-donors, SIN-1 and
      diethylamine/NO (DEA/NO), and of an aqueous solution of nitric oxide on the ACE
      activity in plasma from 3-month old male Sprague-Dawley rats and on ACE purified
      from rabbit lung. SIN-1 significantly inhibited the activity of both enzymes in a
      concentration-dependent way between 1 and 100 microM. DEA/NO inhibited the
      activity of purified ACE from 0.1 microM to 10 microM and plasma ACE, with a
      lower potency, between 1 and 100 microM. An aqueous solution of NO (100 and 150
      microM) also inhibited significantly the activity of both enzymes. Lineweaver
      Burk plots indicated an apparent competitive inhibition of Hip-His-Leu hydrolysis
      by NO-donors. 3. Modulation of ACE activity by NO was also assessed in the rat
      carotid artery by comparing contractions elicited by angiotensin I (AI) and AII.
      Concentration-response curves to both peptides were performed in arteries with
      endothelium in the presence of the guanylyl cyclase inhibitor, ODQ (10 microM),
      and the inhibitor of NO formation, L-NAME (0.1 mM). NO, which is still released
      from endothelium in the presence of 10 microM ODQ, elicited a significant
      inhibition of AI contractions at low concentrations (1 and 5 nM). In the absence
      of endothelium, 1 microM SIN-1 plus 10 microM ODQ, as well as 10 microM DEA/NO
      plus 10 microM ODQ induced a significant inhibition on AI-induced contractions at
      1 and 5 nM and at 1-100 nM, respectively. 4. In conclusion, we demonstrated that
      (i) NO and NO-releasing compounds inhibit ACE activity in a concentration
      dependent and competitive way and that (ii) NO release from endothelium
      physiologically reduces conversion of AI to AII.

PMID- 9641546
TI  - The contribution of nitric oxide to cardiovascular status and responses to
      vasodilators in conscious, hypertensive, transgenic ((mRen-2)27) rats.
AB  - 1. The aim of the study was to measure the regional haemodynamic responses to
      vasodilators, and the effects of nitric oxide (NO) synthase inhibition, in
      conscious, hypertensive, transgenic ((mRen-2)27) rats (TG rats) and normotensive,
      Hannover Sprague-Dawley (SD) rats. 2. The hypotensive response to acetylcholine
      was greater in TG than in SD rats, but the renal vasodilator responses were not
      different. 3. The responses to bradykinin were similar in the two strains, except
      that hindquarters vasodilatation occurred only in SD rats. 4. Salbutamol caused
      smaller renal and hindquarters vasodilatation in TG rats than in SD rats, and
      there was mesenteric vasodilatation only in the latter strain. 5. The hypotensive
      response to sodium nitroprusside was smaller, but the accompanying mesenteric
      vasodilatation was greater, in SD than in TG rats. 6. The contribution of NO to
      the vasodilator responses was taken as the difference between the responses in
      the presence of the NO synthase inhibitor, NG-nitro-L-arginine methylester (L
      NAME), compared to those in the presence of a co-infusion of angiotensin II and
      vasopressin (to match the haemodynamic effects of L-NAME). 7. In TG rats, L-NAME
      caused a greater absolute pressor effect, but a smaller mesenteric
      vasoconstriction, than in SD rats. 8. L-NAME affected the vasodilator responses
      to all the challenges similarly in the two strains. 9. Collectively, the results
      provide no direct evidence for impaired NO-mediated vasodilator mechanisms in TG
      rats. It is feasible that the reduced hindquarters response to bradykinin and the
      reduced renal and hindquarters responses to salbutamol, in TG rats are due to
      abnormal beta2-adrenoceptor-mediated processes.

PMID- 9641547
TI  - Effect of inhibition of tyrosine phosphatases on voltage-operated calcium channel
      currents in rabbit isolated ear artery cells.
AB  - 1. The effect of increasing cellular tyrosine phosphorylation by inhibiting
      endogenous tyrosine phosphatases was examined on voltage-operated calcium channel
      currents in vascular smooth muscle cells. 2. In single ear artery smooth muscle
      cells of the rabbit, studied by the whole cell voltage clamp technique,
      intracellular application of the tyrosine phosphatase inhibitors, sodium
      orthovanadate (100 microM) and peroxyvanadate (100 microM orthovanadate + 1 mM
      H2O2) increased voltage-operated calcium channel currents by 56% and 83%,
      respectively. 3. Bath application of two other membrane permeant tyrosine
      phosphatase inhibitors, phenylarsine oxide (100 microM) and dephostatin (50
      microM) also increased voltage-operated calcium channel currents by 48% and 52%,
      respectively. 4. The selective tyrosine kinase inhibitor, tyrphostin-23 (100
      microM) reduced calcium channel currents by 41%. Pre-incubation with tyrphostin
      23 abolished the effects of peroxyvanadate, phenylarsine oxide and dephostatin on
      calcium channels. 5. Western blot analysis of rabbit ear artery cell lysates
      showed increased tyrosine phosphorylation of several endogenous proteins
      following treatment with peroxyvanadate. 6. These results indicate that a number
      of structurally dissimilar inhibitors of tyrosine phosphatases increase voltage
      operated calcium channel currents in arterial smooth muscle cells presumably due
      to increased tyrosine phosphorylation.

PMID- 9641549
TI  - Differential effects of somatostatin and angiopeptin on cell proliferation.
AB  - 1. Somatostatin (SRIF) exerts antiproliferative effects, and angiopeptin (an
      sst2/sst5 receptor-selective analogue) has recently been evaluated in clinical
      trials for the prophylaxis of restenosis following coronary angioplasty. Using an
      in vitro model of cell growth we have examined the effects of SRIF and
      angiopeptin on cell proliferation in CHO-K1 cells stably transfected with the
      human or rat recombinant sst2 or sst5 receptor and compared these with their
      effects on rat aortic vascular smooth muscle cells (VSMC) expressing endogenous
      somatostatin receptors. 2. In CHO-KI cells, expressing either human or rat
      recombinant sst2 or sst5 receptors, or in rat aortic VSMC, SRIF and angiopeptin
      (0.1-1000 nM) had no effect on basal re-growth of cells into a denuded area of a
      previously confluent monolayer. In contrast, basic fibroblast growth factor
      (bFGF, 10 ng ml(-1)) stimulated re-growth of these cells. 3. SRIF (0.1-1000 nM)
      caused a concentration-dependent inhibition of the bFGF-stimulated re-growth in
      CHO-K1 cells expressing human sst2 (h sst2) or sst5 (h sst5) receptors
      (pIC50=8.05+/-0.03 and 8.56+/-0.12, respectively). In contrast, angiopeptin (0.1
      1000 nM) acted as a partial agonist at the h sst2 receptor (44.6+/-2.7%
      inhibition of the bFGF-stimulated re-growth at 100 nM; pIC50=8.69+/-0.25) but was
      devoid of any agonist activity at the h sst5 receptor. 4. In CHO-K1 cells stably
      expressing rat recombinant sst2 (r sst2) or sst5 (r sst5) receptors, SRIF (0.1
      1000 nM) was able to inhibit the bFGF-stimulated re-growth (pIC50=7.98+/-24 and
      8.50+/-0.12, respectively). Angiopeptin (0.1-1000 nM) caused a concentration
      dependent inhibition of bFGF-stimulated re-growth at the r sst2 receptor
      (pIC50=8.08+/-0.24) but acted as a partial agonist at the r sst5 receptor
      (maximum response= 57.7+/-3.6% inhibition of bFGF-stimulated re-growth at 100 nM;
      pIC50=8.60+/-0.16). 5. Although angiopeptin was inactive as an agonist at the h
      sst5 receptor, 100 nM angiopeptin potently antagonized the SRIF-induced
      inhibition of proliferation in CHO h sst5 (estimated pKB= 10.4+/-0.3). 5
      Hydroxytryptamine (0.1 nM-10 microM) also inhibited bFGF-stimulated re-growth
      (pIC50=8.36+/-0.11) and angiopeptin had no effect on this response (pKB<7). 6.
      SRIF (0.1-1000 nM) caused a concentration-dependent (pIC50=8.04+/-0.08)
      inhibition of bFGF-stimulated re-growth in VSMC, whereas angiopeptin displayed
      weak agonist activity, only inhibiting bFGF-stimulated re-growth at
      concentrations greater than 100 nM. Angiopeptin (100 nM) caused a rightward
      displacement of the concentration-effect curve to SRIF with an estimated pKB
      value of 7.70+/-0.12. 7. These findings suggest that the low intrinsic activity
      of angiopeptin at the h sst2 receptor, combined with its lack of agonist activity
      at the h sst5 receptor, may explain the poor clinical efficacy of angiopeptin in
      trials for coronary artery restenosis, which contrasts with encouraging data
      found in equivalent in vivo animal studies.

PMID- 9641548
TI  - Modulation of extracellular GABA levels in the retina by activation of glial P2X
      purinoceptors.
AB  - 1. In the rat retina, gamma-aminobutyric acid (GABA) released as a transmitter is
      inactivated by uptake mainly into glial cells (Muller cells). Activation of P2
      purinoceptors in Muller cells increases [Ca2+]i and the present study was
      undertaken to see whether this action affected the glial release of [3H]-GABA
      from the superfused rat isolated retina. 2. Adenosine 5'-triphosphate (ATP) and
      the P2X-purinoceptor agonists, alpha,beta-methylene-ATP (alpha,beta-meATP) and
      beta,gamma-methyleneATP (beta,gamma-meATP) significantly increased the KCl-evoked
      release of [3H]-GABA from the retina. 3. Adenosine and the P2Y-purinoceptor
      agonist, 2-chloroATP, had no effect on the KCl-evoked release of [3H]-GABA from
      the retina. However, 2-methylthioATP (2-Me-S-ATP) significantly enhanced the
      evoked release of [3H]-GABA. 4. The effect of ATP on the glial release of [3H]
      GABA was abolished by the P2-antagonist, pyridoxalphosphate-6-azophenyl-2',4'
      disulphonic acid (PPADS). 5. When the superfused retina was exposed to the GABA
      uptake inhibitor, SKF89976A, the enhancing effect of alpha,beta-meATP on the KCl
      evoked release of GABA was abolished. 6. The KCl-evoked release of [3H]-GABA from
      the frog retina and rat cerebrocortical slices, which take up GABA mainly into
      neurones, was not affected by ATP or alpha,beta-meATP. 7. We concluded that the
      glial Muller cells in the rat retina possess P2-receptors, activation of which
      increases the 'release' of preloaded [3H]-GABA apparently by reducing uptake. On
      balance, the results suggest the involvement of P2X-purinoceptors, although we
      cannot exclude the possibility that P2Y-purinoceptors may be involved. Our
      results suggest that ATP, as well as being a conventional transmitter in the
      retina, may be involved in neuronal-glial signalling and modulate the
      extracellular concentration of GABA.

PMID- 9641550
TI  - Superoxide and endothelium-dependent constriction to flow in porcine small
      pulmonary arteries.
AB  - 1. The aim of this study was to determine the response of porcine small pulmonary
      arteries to intralumenal flow and to identify the cellular mechanisms and
      potential mediators involved in the response. 2. Porcine small pulmonary arteries
      were isolated from a branch of the main intrapulmonary artery of the lower lung
      lobe and studied in a perfusion myograph system that allowed independent control
      of transmural pressure and intralumenal flow. At a transmural pressure of 20
      mmHg, the baseline internal diameter (BID) of the arteries was 251.2+/-16.1
      microm (n=16). 3. Under quiescent conditions or during constriction with U46619
      to approximately 60% of BID, intralumenal flow caused reversible constriction in
      arteries with endothelium (in the presence of U46619, flow decreased diameter
      from 60.0+/-2.5% to 49.5+/-3.0% BID at 10 microl min(-1), n=16, P<0.05) but no
      change in diameter of arteries without endothelium. 4. In the presence of
      superoxide dismutase (SOD, 150 u ml(-1)), the response to flow was converted from
      constriction to vasodilatation (in presence of U46619 and SOD, flow increased
      diameter from 54.2+/-3.4% to 76.7+/-4.5% BID at 10 microl min(-1), n=10, P<0.05).
      Inhibition of NO synthase with L-NAME (3 x 10(-5) M) abolished the flow-induced
      vasodilatation occurring in the presence of SOD and the flow-induced constriction
      occurring in the absence of SOD. In arteries with endothelium, L-NAME (3 x 10(-5)
      M) caused significant vasoconstriction, whereas SOD did not alter vasomotor tone.
      5. Acetylcholine (10(-8) to 10(-6) M) caused endothelium-dependent relaxation of
      small pulmonary arteries that was not significantly affected by SOD (150 u ml(
      1)) but was inhibited by L-NAME (3 x 10(-5) M). 6. These results suggest that in
      small, porcine, isolated pulmonary arteries, intralumenal flow increases the
      production of NO but this is obscured by the generation of superoxide which
      causes vasoconstriction.

PMID- 9641551
TI  - P2X receptors in cochlear Deiters' cells.
AB  - 1. The ionotropic purinoceptors in isolated Deiters' cells of guinea-pig cochlea
      were characterized by use of the whole-cell variant of the patch-clamp technique.
      2. Extracellular application of adenosine 5'-triphosphate (ATP) induced a dose
      dependent inward current when the cells were voltage-clamped at -80 mV. The ATP
      induced current showed desensitization and had a reversal potential around -4 mV.
      3. Increasing intracellular free Ca2+ by decreasing the concentration of EGTA in
      the pipette solution reduced the amplitude of the ATP-gated current. 4. The order
      of agonist potency was: 2-methylthioATP (2-meSATP)>ATP>benzoylbenzoyl-ATP
      (BzATP)>alpha,beta-methyleneATP (alpha,beta,meATP>adenosine 5'-diphosphate
      (ADP)>uridine 5'-triphosphate (UTP)>adenosine 5'-monophosphate (AMP)=adenosine
      (Ad). 5. Pretreatment with forskolin (10 microM), 8-bromoadenosine-3',5'
      cyclophosphate (8-Br-cyclic AMP, 1 mM), 3-isobutyl-1-methylxanthine (IBMX, 1 mM)
      or phorbol-12-myristate-13-acetate (PMA, 1 microM) reversibly reduced the ATP
      induced peak current. 6. The results are consistent with molecular biological
      data which indicate that P2X2 purinoceptors are present in Deiters' cells. In
      addition, the reduction of the ATP-gated current by activators of protein kinase
      A and protein kinase C indicates that these P2X2 purinoceptors can be
      functionally modulated by receptor phosphorylation.

PMID- 9641553
TI  - Different effects of gadolinium on I(KR), I(KS) and I(K1) in guinea-pig isolated
      ventricular myocytes.
AB  - 1. Using the whole cell configuration of the patch clamp technique, we studied
      the potential blocking effects of gadolinium (1 microM to 1 mM) on potassium
      currents: I(KR), I(KS) and I(K1). The study was performed on guinea-pig isolated
      ventricular myocytes. 2. The background current, I(K1) was insensitive to Gd3+.
      Thus, we found that no obvious screening of surface charges was visible with
      concentrations of Gd3+ up to 100 microM. 3. By use of three different protocols:
      tail currents fitting, analysis of envelope of tails and electrophysiological
      dissection, we found that I(KR) was the only component of IK that was sensitive
      to Gd3+. The sensitivity was apparently different depending on the protocol used.
      4. Comparison of the results obtained with the different protocols revealed that
      the rapid component of I(KR) is more sensitive to Gd3+ than the slow one. 5. Of
      the different protocols used to distinguish between I(KR) and I(KS), the
      electrophysiological dissection seems to be the more accurate.

PMID- 9641552
TI  - Respiratory and cardiovascular effects of the mu-opioid receptor agonist
      [Lys7]dermorphin in awake rats.
AB  - 1. Changes in respiratory variables, arterial blood pressure and heart rate were
      studied in awake rats after injection of the opioid peptide [Lys7]dermorphin and
      its main metabolites, [1-5]dermorphin and [1-4]dermorphin. 2. Fifteen minutes
      after injection, doses of [Lys7]dermorphin producing antinociception (i.c.v., 36
      120 nmol; s.c., 0.12-4.7 micromol kg(-1)) significantly increased respiratory
      frequency and minute volume of rats breathing air or hypoxic inspirates. This
      respiratory stimulation was reversed to depression by the 5-HT receptor
      antagonist ritanserin (2 mg kg(-1), s.c.), was blocked by naloxone (0.1 mg kg(
      1), s.c.), significantly reduced by the mu1 opioid receptor antagonist
      naloxonazine (10 mg kg(-1), s.c., 24 h before) but unaffected by peripherally
      acting opioid antagonist naloxone methyl bromide (3 mg kg(-1), s.c.). Forty five
      minutes after injection, doses of the peptide producing catalepsy (s.c., 8.3-14.2
      micromol kg(-1), i.c.v., 360 nmol) significantly reduced respiratory frequency
      and volume of rats breathing air and blocked the hypercapnic ventilator response
      of rats breathing from 4% to 10% CO2. I.c.v. administration of [1-5]dermorphin
      and [1-4]dermorphin (from 36 to 360 nmol) never stimulated respiration but
      significantly reduced basal and CO2-stimulated ventilation. Opioid respiratory
      depression was only antagonized by naloxone. 3. In awake rats, [Lys7]dermorphin
      (0.1-1 mg kg(-1), s.c.) decreased blood pressure. This hypotensive response was
      abolished by naloxone, reduced by naloxone methyl bromide and unaffected by
      naloxonazine. 4. In conclusion, the present study indicates that analgesic doses
      of [Lys7]dermorphin stimulate respiration by activating central mu1 opioid
      receptors and this respiratory stimulation involves a forebrain 5
      hydroxytryptaminergic excitatory pathway.

PMID- 9641554
TI  - Inhibition of nitric oxide generation unmasks vascular dysfunction in insulin
      resistant, obese JCR:LA-cp rats.
AB  - 1. The effects of nitric oxide (NO) on vascular reactivity and platelet function
      in the obese (cp/cp) and lean (+/?) JCR:LA-cp rats were investigated. 2.
      Phenylephrine (PE; 0.1 nM-10 microM) induced contraction of isolated aortic rings
      in both genotypes (cp/cp and +/?) of JCR:LA-cp rats. The sensitivity to
      contraction with PE was enhanced in cp/cp compared with +/? rings. Rings from
      both genotypes showed an increased contraction upon removal of the endothelium.
      3. Acetylcholine (ACh; 0.1 nM-10 microM)-induced endothelium-dependent relaxation
      of rings was not significantly different in the two genotypes. Both were
      inhibited to a similar extent by NG-nitro-L-arginine methyl ester (L-NAME; 0.01-1
      mM) when administered in vitro. 4. The nitric oxide synthase (NOS) inhibitor (L
      NAME; 0.3, 1 or 3 mg ml(-1), p.o.) when administered in vivo increased blood
      pressure in cp/cp rats but not in +/? rats. 5. L-NAME resulted in greater
      inhibition of ACh-induced relaxation in cp/cp rings compared with +/? rings. 6. L
      NAME treatment in vivo caused a decrease in cyclic GMP and NOS activity in rings
      from cp/cp but not +/? rats. 7. The NO donor, S-nitroso-N-acetyl-DL-penicillamine
      (SNAP; 0.1 nM-10 microM)-induced relaxation of rings from +/? rats, an effect
      enhanced by the treatment with L-NAME in vivo. 8. Oral administration of L-NAME
      did not enhance the vasorelaxant effect of SNAP on rings of aorta from cp/cp
      animals. 9. Platelet aggregation and NOS activity were similar in both genotypes
      and were not modified by oral administration of L-NAME. 10. These results show
      that unimpaired generation of NO is crucial for maintenance of vascular tone
      particularly under conditions of vascular insult exemplified by insulin
      resistance, obesity and dyslipidemia detected in cp/cp rats.

PMID- 9641555
TI  - Gabapentin potentiation of the antiepileptic efficacy of vigabatrin in an in
      vitro model of epilepsy.
AB  - 1. An enhancement of promoted release of gamma-aminobutyric acid (GABA) and a
      change in GABA-metabolism have been suggested as mechanisms of action of
      gabapentin. Vigabatrin is supposed to act mainly via inhibition of GABA
      transaminase but it also interferes with GABA-release and GABA-uptake. On the
      basis of these mechanisms of action, a pharmacodynamic interaction of the two
      antiepileptic drugs could be supposed which might be of relevance in the sense of
      a rational polypharmacy. 2. To address the aforementioned hypothesis, experiments
      were carried out on hippocampal slices (n=107) of guinea-pigs (n=70).
      Epileptiform field potentials (e.f.p.) were induced by omission of magnesium from
      the bath solution and recorded in the stratum pyramidale of the CA3 region.
      Gabapentin (30-600 microM; 5.1-102.72 microg ml(-1)), vigabatrin (50-200 microM,
      6.45-25.8 microg ml(-1)) and the GABA(A)-receptor antagonist bicuculline (100
      microM) were added to the bath solution for 3 h. 3. Gabapentin, in concentrations
      up to 600 microM, failed to decrease the repetition rate or duration of e.f.p.
      (n=19). However, vigabatrin, evoked a dose-dependent reduction of the repetition
      rate of e.f.p. For a concentration of 100 microM (12.9 microg ml(-1)) there was a
      reduction down to 48+/-5% (mean+/-s.e.mean) of the initial value within 3 h
      (n=11). With simultaneous administration of vigabatrin (100 microM) and
      gabapentin (60 microM) for 3 h (n=15), the repetition rate of e.f.p. decreased
      down to 8+/-3%, which is significantly different from the values obtained after
      administration of 100 microM vigabatrin alone (P<0.0001). Both, the antiepileptic
      effect of vigabatrin alone and the enhancement by gabapentin were blocked by the
      GABA(A)-receptor antagonist bicuculline (100 microM, n=16). 4. These results
      demonstrate that gabapentin is able to augment the antiepileptic effects of
      vigabatrin significantly. It is possible that a change in the GABA-release
      machinery is induced by vigabatrin which then can be augmented by gabapentin.

PMID- 9641556
TI  - Characterization of the phencyclidine-induced increase in prefrontal cortical
      dopamine metabolism in the rat.
AB  - 1. We have investigated the effects of a schizophrenomimetic drug phencyclidine
      (PCP) and N-methyl-D-aspartate (NMDA)-related agents alone or in combination on
      dopamine metabolism in the medial prefrontal cortex and striatum of the rats by
      measuring the tissue concentrations of dopamine and its metabolite, 3,4
      dihyroxyphenylacetic acid (DOPAC), and the rate of dopamine disappearance
      (dopamine utilization) after its synthesis inhibition. 2. Systemic injection of
      PCP and selective, non-competitive, NMDA antagonists caused an increase of both
      tissue concentrations of DOPAC and dopamine utilization in the prefrontal cortex
      but not in the striatum. The PCP-induced augmentation of cortical dopamine
      metabolism was not influenced by selective lesion of ascending noradrenergic
      neurones. 3. Intra-prefrontal cortical infusion of PCP or selective competitive
      or non-competitive antagonists of the NMDA receptor mimicked the ability of
      systemic PCP injection to enhance DOPAC levels and dopamine utilization in the
      prefrontal cortex. However, an NMDA antagonist injected into the cell body area
      of the mesocortical dopaminergic neurones failed to affect dopamine metabolism in
      the prefrontal cortex. 4. The increasing effects of PCP and selective NMDA
      antagonists on cortical dopamine utilization were not additive, although a
      dopamine receptor antagonist, haloperidol, still accelerated the disappearance of
      dopamine, even in the presence of PCP. 5. Intra-cortical or intra-ventricular
      infusion of NMDA or D-alanine but not L-alanine, attenuated the ability of
      systemic PCP administration to facilitate prefrontal dopamine utilization. 6.
      These data suggest that PCP might activate prefrontal cortical dopaminergic
      neurones, at least in part, by blocking the NMDA receptor in the prefrontal
      cortex which participates in a tonic inhibitory control of the mesoprefrontal
      dopaminergic projections.

PMID- 9641557
TI  - Investigation of the actions and antagonist activity of some polyamine analogues
      in vivo.
AB  - 1. The ability of three putative polyamine antagonists to antagonize behavioural
      changes induced by spermine was assessed. 2. Injection of an excitotoxic dose of
      spermine (100 microg, i.c.v.) in mice results in the development of a
      characteristic behavioural profile, which has two temporally distinct phases. The
      early events include clonic convulsions, and the later, more general excitation,
      includes tremor and culminates in the development of a fatal tonic convulsion. 3.
      Co-administration of arcaine (25 microg, i.c.v.) potentiated the early phase
      effects after spermine injection, but antagonized the development of spermine
      induced tonic convulsions. A larger dose of arcaine (50 microg, i.c.v.) given
      alone resulted in the development of spermine-like body tremor and convulsions.
      It therefore appears that arcaine is not a pure polyamine antagonist in vivo, but
      may be a partial agonist. 4. Similarly, 1,10-diaminodecane appeared to act as a
      partial agonist in vivo, although it was less potent than arcaine. 5. In
      contrast, diethylenetriamine (DET) effectively inhibited the development of the
      early effects of spermine, but was ineffective against the spermine-induced CNS
      excitation and tonic convulsions. 6. It is concluded that none of the putative
      polyamine antagonists tested behaved as effective polyamine antagonists in vivo,
      although each produced some antagonism.

PMID- 9641558
TI  - Modulation of striatal quinolinate neurotoxicity by elevation of endogenous brain
      kynurenic acid.
AB  - 1. Nicotinylalanine, an inhibitor of kynurenine metabolism, has been shown to
      elevate brain levels of endogenous kynurenic acid, an excitatory amino acid
      receptor antagonist. This study examined the potential of nicotinylalanine to
      influence excitotoxic damage to striatal NADPH diaphorase (NADPH-d) and gamma
      aminobutyric acid (GABA)ergic neurones that are selectively lost in Huntington's
      disease. 2. A unilateral injection of the N-methyl-D-aspartate (NMDA) receptor
      agonist, quinolinic acid, into the rat striatum produced an 88% depletion of
      NADPH-d neurones. Intrastriatal infusion of quinolinic acid also produced a dose
      dependent reduction in striatal GABA content. 3. Nicotinylalanine (2.3, 3.2, 4.6,
      6.4 nmol 5 microl(-1), i.c.v.) administered with L-kynurenine (450 mg kg(-1)), a
      precursor of kynurenic acid, and probenecid (200 mg kg(-1)), an inhibitor of
      organic acid transport, 3 h before the injection of quinolinic acid (15 nmol)
      produced a dose-related attenuation of the quinolinic acid-induced loss of NADPH
      d neurones. Nicotinylalanine (5.6 nmol 5 microl(-1)) in combination with L
      kynurenine and probenecid also attenuated quinolinic acid-induced reductions in
      striatal GABA content. 4. Nicotinylalanine (4.6 nmol, i.c.v.), L-kynurenine alone
      or L-kynurenine administered with probenecid did not attenuate quinolinic acid
      induced depletion of striatal NADPH-d neurones. However, combined administration
      of kynurenine and probenecid did prevent quinolinic acid-induced reductions in
      ipsilateral striatal GABA content. 5. Injection of nicotinylalanine, at doses
      (4.6 nmol and 5.6 nmol i.c.v.) which attenuated quinolinic acid-induced striatal
      neurotoxicity, when combined with L-kynurenine and probenecid produced increases
      in both whole brain and striatal kynurenic acid levels. Administration of L
      kynurenine and probenecid without nicotinylalanine also elevated kynurenic acid,
      but to a lesser extent. 6. The results of this study demonstrate that
      nicotinylalanine has the potential to attenuate quinolinic acid-induced striatal
      neurotoxicity. It is suggested that nicotinylalanine exerts its effect by
      increasing levels of endogenous kynurenic acid in the brain. The results of this
      study suggest that agents which influence levels of endogenous excitatory amino
      acid antagonists such as kynurenic acid may be useful in preventing excitotoxic
      damage to neurones in the CNS.

PMID- 9641559
TI  - Inhibition of NMDA-gated ion channels by the P2 purinoceptor antagonists suramin
      and reactive blue 2 in mouse hippocampal neurones.
AB  - 1. The action of suramin and reactive blue 2 on N-methyl-D-aspartate (NMDA)
      activated ion current was studied in mouse hippocampal neurones in culture by use
      of whole-cell patch-clamp recording. 2. Suramin and reactive blue 2 inhibited
      steady-state current activated by 25 microM NMDA with IC50 values of 68 and 11
      microM, respectively. 3. Reactive blue 2 produced a gradual decline of NMDA
      activated current to a steady-state, but this slow onset was not an indication of
      use-dependence, as it could be eliminated by exposure to reactive blue 2 before
      NMDA application. In addition, NMDA-activated current recovered completely from
      inhibition by reactive blue 2 in the absence of agonist. 4. The slow onset of
      inhibition by reactive blue 2 was not apparently due to an action at an
      intracellular site, as inclusion of 250 microM reactive blue 2 in the recording
      pipette did not alter inhibition by 25 microM reactive blue 2 applied externally.
      5. Reactive blue 2 and suramin inhibited NMDA-gated channels in a voltage
      independent manner. 6. Reactive blue 2, 25 microM, decreased the maximal response
      to NMDA from 1441 to 598 pA without changing its EC50. In contrast, 75 microM
      suramin increased the EC50 for NMDA from 13 to 35 microM, and decreased the
      maximal response to NMDA from 1822 to 1498 pA. Schild analysis of suramin
      inhibition of NMDA-activated current yielded a nonlinear plot. 7. Both agents
      decreased the maximal response to glycine without altering its EC50. 8. Suramin
      and reactive blue 2 appear to inhibit NMDA receptor-channels in a manner that is
      noncompetitive with respect to both NMDA and glycine. However, inhibition by
      suramin differed from that by reactive blue 2, in that suramin significantly
      increased the EC50 of NMDA.

PMID- 9641560
TI  - The profile of sabcomeline (SB-202026), a functionally selective M1 receptor
      partial agonist, in the marmoset.
AB  - 1. Sabcomeline (SB-202026, 0.03 mg kg(-1), p.o.), a potent and functionally
      selective M1 receptor partial agonist, caused a statistically significant
      improvement in the performance of a visual object discrimination task by
      marmosets. No such improvement was seen after RS86 (0.1 mg kg(-1), p.o.). 2.
      Initial learning, which only required an association of object with reward and an
      appropriate response to be made, was not significantly affected. Reversal
      learning, which required both the extinction of the previously learned response
      and the acquisition of a new response strategy, was significantly improved after
      administration of sabcomeline (0.03 mg kg(-1), p.o.). 3. Sabcomeline (0.03 and
      0.1 mg kg(-1), p.o.) had no significant effect on mean blood pressure measured
      for 2 h after administration in the conscious marmoset. 4. Sabcomeline (0.03 mg
      kg(-1), p.o.) caused none of the overt effects such as emesis or behaviours often
      seen after the administration of muscarinic agonists, e.g. face rubbing and
      licking. 5. This is the first study to demonstrate cognitive enhancement by a
      functionally selective M1 receptor partial agonist in a normal (i.e. non
      cognitively impaired) non-human primate and this effect was seen at a dose which
      did not cause side effects. 6. Perseverative behaviour and deficient acquisition
      of new information are seen in patients with Alzheimer's disease (AD). Therefore
      the data suggest that sabcomeline might be of therapeutic benefit in the
      treatment of AD.

PMID- 9641561
TI  - Hepatobiliary and intestinal clearance of amphiphilic cationic drugs in mice in
      which both mdr1a and mdr1b genes have been disrupted.
AB  - 1. We have used mice with homozygously disrupted mdr1a and mdr1b genes (mdr1a/1b
      (-/-) mice) to study the role of the mdr1-type P-glycoprotein (P-gp) in the
      elimination of cationic amphiphilic compounds from the body. These mice lack drug
      transporting P-gps, but show no physiological abnormalities under laboratory
      conditions and have normal bile flow. 2. 3H-labelled cationic drugs were
      administered intravenously (i.v.) to mice as a single bolus dose and the
      disposition of the studied cationic drugs was investigated by focusing on drug
      secretion into bile, intestinal lumen and urine. 3. Hepatobiliary secretion of
      the investigated cationic drugs was profoundly reduced in mice devoid of the mdr1
      type P-gps. In fact, the cumulative biliary output, measured during 1 h, of the
      small type 1 compounds tri-butylmethyl ammonium (TBuMA) and azidoprocainamide
      methoiodide (APM), as well as of the more bulky type 2 cationic drug vecuronium,
      was reduced by at least 70% in the mdrla/lb (-/-) mice compared to wild-type. 4.
      The intestinal secretion of TBuMA, APM and vecuronium was also profoundly reduced
      in mdrla/lb (-/-) mice compared to wild-type mice. The absence of the mdrl-type P
      gp resulted in virtual elimination of intestinal secretion of TBuMA and APM (>90%
      reduced as compared to wild-type (P=0.0001 and 0.0022, respectively)). The
      intestinal secretion of the type 2 cation drug vecuronium was reduced by 58%
      (P=0.0004) compared to the wild-type mice. 5. Increased renal clearances of both
      the type 1 compounds TBuMA and APM and also of the type 2 cationic compound
      vecuronium in the mdrla/lb (-/-) mice were observed. Furthermore, the balance
      between hepatic, intestinal and renal clearances of small type 1 organic cations
      clearly shifted towards a predominant role for renal clearance. Increased renal
      clearance may be explained by (over)expression of additional mechanisms for renal
      organic cation secretion, alternatively they may also point to an as yet
      undefined role of P-glycoprotein in kidney physiology and renal secretory
      function. 6. We conclude that the elimination from the body of a broad spectrum
      of cationic amphiphilic drugs via liver and intestine, is largely dictated by the
      activity of mdrl-type P-glycoproteins.

PMID- 9641562
TI  - Genes for asthma on chromosome 11: an update.

PMID- 9641563
TI  - Nasal immunotherapy--not to be sneezed at.

PMID- 9641564
TI  - Pollinosis in the southern Europe--Mediterranean area.

PMID- 9641565
TI  - Exclusion of chromosome 11q and the FcepsilonRI-beta gene as aetiological factors
      in allergy and asthma in a population of Dutch asthmatic families.
AB  - BACKGROUND: The beta subunit of the high-affinity receptor for IgE (FcepsilonRI
      beta) is localized to chromosome 11q13 and has been reported by Cookson et al. to
      be in close genetic linkage with a gene for atopy. A maternally inherited
      association was found between the presence of a variant of FcepsilonRI-beta,
      Ile181Leu, and high total serum IgE levels (IgE > 100 IU). In a previous study of
      20 Dutch families, we found no evidence for linkage of atopy or bronchial
      hyperresponsiveness (BHR) to chromosome 11q. OBJECTIVE: Recently segregation
      analysis in 92 families has given us evidence for two independent major loci
      accounting for 78% of the observed variance in total serum IgE levels, and
      linkage analysis using both sib-pair and LOD score methods has identified one
      major locus for regulation of IgE levels and BHR near the cytokine gene complex
      on chromosome 5q. The objective of this study is to pursue the identification of
      the second major locus. METHODS: We have studied markers in the area of the high
      affinity IgE receptor (FcepsilonRI-beta) on chromosome 11q (D11S1314, FcepsilonRI
      beta and D11S987) in 83 families for whom DNA was available. Furthermore, our
      families have been examined for variance in the FcepsilonRI-beta gene,
      specifically for Leu181 and Leu181/Leu183 mutations. RESULTS: By sib-pair
      analysis, there is no evidence for linkage of total serum IgE levels or number of
      positive skin tests to these markers in our population. Similar negative results
      were obtained for affected sib-pair analysis of BHR, with the exception of
      D11S1314, which was significant at P=0.046. The FcepsilonRI-beta gene in 36
      female probands, 44 male probands and 46 female spouses was sequenced for these
      mutations. For each of these 126 individuals sequencing of FcepsilonRI-beta
      demonstrated a wild-type sequence pattern, with no mutations found in anyone,
      male or female. CONCLUSION: We are unable to confirm the presence of significant
      mutations in FcepsilonRI-beta gene in our population, and we cannot confirm that
      the FcepsilonRI-beta gene is crucial to the pathogenesis of allergic inflammation
      in asthma.

PMID- 9641566
TI  - Decrease of allergen-specific T-cell response induced by local nasal
      immunotherapy.
AB  - BACKGROUND: The clinical efficacy and safety of local nasal immunotherapy (LNIT)
      with lyophilized 'macronized' powder has been demonstrated. However, the
      immunological changes possibly induced by LNIT which may account for the clinical
      improvement are still unclear. OBJECTIVE: To investigate the effects of a
      successful LNIT-treatment on the allergen-driven T cell response, cytokine
      secretion and IgE and IgG antibody production. METHODS: Three groups (untreated,
      subcutaneous immunotherapy- SIT- and LNIT-treated) of grass-sensitive patients
      suffering from seasonal rhinitic symptoms were ramdomized for the 2-year study.
      The proliferative response of PBMC to purified Rye-1 allergen and serum levels of
      grass-specific IgE and IgG were evaluated before treatment and during the 2-year
      subsequent pollination periods. The proliferative response of allergen-specific
      short-term T-cell lines, as well as production of allergen-driven cytokine by
      PBMC, were also assessed. RESULTS: Both SIT and LNIT induced a significant
      reduction of symptom scores during the pollination season. SIT, but not LNIT,
      induced a significant change in serum levels of allergen-specific IgE and IgG
      antibody. By contrast, both SIT and LNIT reduced the increase of the
      proliferative response of allergen-specific T cells driven by natural allergen
      exposure and significantly decreased T cell proliferation to low doses of
      allergen, as shown also by the mitogenic index of allergen-specific T-cell lines.
      A reduced IL-4 and IFNgamma production by PBMC of LNIT- and SIT-treated patients
      was also observed in the absence of a clearcut TH2-TH1 switch. CONCLUSIONS: These
      data suggest that a common mechanism of both LNIT and SIT is the induction of T
      cell tolerance, thus providing a rational basis to explain why LNIT may be
      clinically successful in allergic patients with rhinits.

PMID- 9641567
TI  - Olive pollen allergy: searching for immunodominant T-cell epitopes on the Ole e 1
      molecule.
AB  - BACKGROUND: The amino-acid and nucleotide sequence of Ole e 1 (the major antigen
      of olive pollen) has been described and the IgE antibody response to this major
      allergen was associated with DR7/DQ2 antigens. With this previous data we try to
      define the T-cell epitopes implicated in Ole e 1 reactivity. OBJECTIVES: To study
      the recognition of T cells (derived from allergic and non-allergic Ole e 1
      patients) to Ole e 1 synthetic peptides in order to define immunodominant T-cell
      epitopes. METHODS: We have compared the proliferative response of the peripheral
      blood mononuclear cells from Ole e 1 sensitized patients vs. non-sensitized
      controls, induced by 14 Ole e 1 synthetic peptides. Thirty subjects were
      classified in two groups: group 1 (non-responders against Ole e 1, n=16) and
      group 2 (Ole e 1 responders, n=14), according to their clinical parameters and
      the presence or not in their sera of the significant Ole e 1 IgE antibody levels.
      RESULTS: Our results shown that it is possible to find T cells reactive to Ole e
      1 peptides in patients with and without significant levels of Ole e 1 IgE
      antibodies. However, the percentage of response was higher in patients with IgE
      antibodies 71.4% vs 25%), and the recognition profile was different: the control
      group showed a broad reactivity pattern, in contrast, the response by the 'Ole e
      1 responders' group was mainly directed against three peptides of the carboxi
      terminal region, peptides 10 (91-102), 12 (109-120) and 13 (119-130), with a
      response frequency of 35.7, 28.5 and 28.5%, respectively. By direct and
      inhibition test no antibody response was found against the synthetic peptides.
      CONCLUSIONS: Our data suggest that the regions between 91 and 102 and 109-130
      aminoacids on the Ole e 1 molecule are immunodominant T-cell epitopes. These
      epitopes are not recognized by IgE antibodies.

PMID- 9641568
TI  - Preserved epitope-specific T cell activation by recombinant Bet v 1-MBP fusion
      proteins.
AB  - BACKGROUND: Allergen-specific T cells play an important role in the allergic
      immune response, and are thought to be the principal target in specific
      immunotherapy. OBJECTIVE: The aim of the present study was to evaluate if fusion
      proteins of allergens with bacterial proteins can be used to activate and bias
      allergen-specific T cells, and to characterize T cell epitopes. METHODS: The
      complete gene of Bet v 1, the major birch pollen allergen, was amplified by PCR
      from birch pollen mRNA, and cloned in pKK223-3. The complete gene or truncated
      sequences were transferred to pMAL-c and expressed in E. coli as fusion proteins
      with maltose binding protein (MBP). The complete fusion protein, and the
      truncated fusion proteins were used for studies with Bet v 1-specific T cells.
      RESULTS: Bet v 1-specific T cells reacted similarly with purified and crude Bet v
      1-MBP proteins. Therefore, crude preparations were used to study the epitope
      specificity of 11 Bet v 1-specific T cell clones. Six distinct T cell epitopes
      were determined in this way. Interestingly, the T cell epitope of three T cell
      clones, that did not react with synthetic peptides in a previous study, was
      identified. In addition, the presence of MBP as a fusion partner to Bet v 1 was
      shown to influence TH2/TH1 cytokine production in T cell lines, but not in
      established T cell clones. CONCLUSION: Using crude preparations of recombinant
      fusion proteins of Bet v 1 with MBP, multiple T cell epitopes were identified in
      Bet v 1. As T cell activation is preserved in this system, the generation of
      recombinant allergens with TH1-inducing proteins as fusion partners might be
      considered as a T-cell targeted approach for specific immunotherapy.

PMID- 9641569
TI  - Identification of HLA-DR and -DQ alleles conferring susceptibility to pollen
      allergy and pollen associated food allergy.
AB  - BACKGROUND: Allergenic crossreactivity of pollen and foods due to the antigeneic
      similarity of oligopeptides is a well established clinical phenomenon. OBJECTIVE:
      To determine the immunopathological relevance of antigen presentation, we
      analysed the HLA class-II genotype of patients with either pollen allergy or
      pollen associated food allergy. METHODS: One hundred and twenty patients with
      pollen allergy and 80 patients with pollen associated food allergy were evaluated
      by skin- prick tests, RAST, and HLA class-II genotyping. The control population
      comprised 4251 healthy blood and bone marrow donors. RESULTS: Monovalent pollen
      allergy was observed in 57% (n=68) of patients with pollinosis (57x grass pollen,
      11x birch pollen), but only in 15% (n=12) of patients with food allergy (9x grass
      pollen, 3x birch pollen). Hazelnut (71%), almond (65%), walnut (44%) and apple
      (41%) were the most common food allergens and frequently associated with birch
      pollen allergy. Grass pollen allergy was associated with an increased frequency
      of HLA-DQB1*0301 (RR=2.3; EF=0.4; P=0.0016) when compared with the control
      population. HLA-DRB *08 conferred a sixfold higher risk for peanut allergy
      (EF=0.3; P=0.0013) and -DRB1*12 a 13-fold higher risk for carrot allergy (EF=0.3;
      P<0.000001). The differences on allele frequencies detected among patients with
      food allergies diminished or turned statistically insignificant when their
      genotypes were directly compared to those of patients with the corresponding
      pollen allergies. This was found in the case of birch pollen associated hazel nut
      allergy for the extended haplotype HLA-DRB1*01, -DQA1*0101, -DQB1*0501 as well as
      in grass pollen associated peanut allergy for HLA-DRB1*08 (from RR=6, P=0.0013 to
      insignificant) and in birch pollen associated carrot allergy for HLA-DRB1*12
      (from RR=13, P < 0.000001 to insignificant). CONCLUSION: We were able to identify
      HLA class-II alleles associated with some allergies thus indicating that these
      alleles might confer susceptibility to the respective allergens. Similarities at
      the level of the HLA class-II genotype parallel the empirical finding of distinct
      cross-reactivity patterns thus complementing investigations of IgE specificities.
      Our observations provide evidence for the major importance of antigen
      presentation on the manifestation of distinct crossreactivity patterns.

PMID- 9641570
TI  - Beta2-adrenoceptor polymorphisms are in linkage disequilibrium, but are not
      associated with asthma in an adult population.
AB  - OBJECTIVE: To determine the association between the beta2-adrenoceptor
      polymorphisms at amino acids 16 and 27 and markers of allergic disease and asthma
      per se in a random adult population, and to determine the degree of linkage
      disequilibrium existing between polymorphisms at amino acid positions 16, 27, 164
      and nucleic acid residue 523. METHODS: We measured serum IgE, skin-prick test
      positivity, atopy, bronchial hyperreactivity, wheeze and asthma (self-reported
      and doctor-diagnosed), and determined beta2-adrenoceptor genotype by allele
      specific oligonucleotide hybridization, in 630 adults aged between 18 and 70,
      selected from the electoral role in a local health authority in Nottingham.
      RESULTS: Homozygotes for the Glycine 16 polymorphism had a significantly higher
      incidence of atopy (chi2=6.44 (Pearson's), P=0.04). We also observed a
      significant association between the Glycine 16 allele and atopy (chi2=4.13
      (Pearson's), P=0.04), when we assumed the Glycine 16 allele to operate in a
      dominant mode. No other significant associations between beta2-adrenoceptor
      polymorphisms and markers of allergic disease and asthma per se were observed.
      Marked linkage disequilibrium exists between the beta2-adrenoceptor polymorphisms
      at amino acid 16 and 27 (D=0.38, chi2 P<0.0001), and between the beta2
      adrenoceptor polymorphisms at amino acid 27 and nucleic acid residue 523 (C-A)
      (D=0.36, chi2 P<0.0001). CONCLUSION: There is no consistent association between
      beta2-adrenoceptor polymorphisms and the risk of developing allergic disease or
      asthma per se in this adult sample. Marked linkage disequilibrium exists between
      the amino acid 16 and 27 polymorphisms, and also between the amino acid 27
      polymorphism and the nucleic acid residue 523 (C-A) polymorphism. This
      polymorphism accounts for the Ban 1 RFLP previously described at the beta2
      adrenoceptor locus on chromosome 5q 31.

PMID- 9641571
TI  - Association of asthma and the interleukin-4 promoter gene in Japanese.
AB  - BACKGROUND: Susceptibility to the development of asthma and other atopic diseases
      is known to be associated with genetic components. Several investigator have
      linked the interleukin-4 (IL-4) gene and nearby markers located on chromosome 5
      to atopy and asthma. Recent study has demonstrated that the T allele of a
      polymorphism in the IL-4 gene promoter region (C-590T) is associated with
      elevated levels of total serum IgE. OBJECTIVE: The objective of this study was to
      evaluate the possible role of this IL-4 polymorphism (C-590T) in modulating the
      allergic response and asthma in Japanese children. METHODS AND RESULTS: The study
      was conducted in two different populations: families ascertained through
      asthmatic children (asthmatic group, 306 members) in whom linkage of asthma and
      atopy to chromosome 5q31-33 is suggested and a random general population (control
      group, 215 members). The IL-4 C-590T polymorphism was genotyped by PCR
      restriction fragment length polymorphism analysis. Frequency of the T allele was
      0.73 in the asthmatic group and 0.70 in the control group. No significant
      difference in the levels of total serum IgE and specific IgE to house dust mite
      was observed between subjects with homozygote for the C allele, a heterozygote
      and a homozygote for the T allele by intrafamilial and interfamilial comparisons.
      Using the transmission disequilibrium test, however, we found a significantly
      frequent transmission of the T allele to asthmatic children (chi2=5.72, P=0.023).
      CONCLUSION: Our data suggest that the IL-4 promoter C-590T polymorphism may be
      associated with the development of asthma in Japanese children, but not through
      modulating total serum IgE levels.

PMID- 9641572
TI  - Validation of a screening questionnaire for atopy with serum IgE tests in a
      population of pregnant Dutch women.
AB  - BACKGROUND: We have started a large birth cohort study in which pregnant women
      with and without atopy are differentially included. In view of the large number
      of subjects to be screened (12000), a simple questionnaire was developed for the
      assessment of atopy in pregnant women. OBJECTIVE: The objective of our study was
      to evaluate the efficacy of a questionnaire using serum IgE tests. METHODS:
      During a antenatal visit to the midwife clinic, 175 expecting mothers completed a
      questionnaire and from each subject blood was obtained in which total and
      specific IgE against house dust mite, cat, dog, birch and grass was determined.
      RESULTS: When atopy was defined as the presence of a positive test for IgE
      against at least one allergen, seven questions from the questionnaire had a
      sensitivity and specificity of 55.0% and 88.7%, respectively. With the use of the
      questionnaire it was possible to select about 50% of the subjects with specific
      IgE to one or more common inhalant allergens. The positive predictive value of
      the screening questions was 71.7%. Taking total IgE into account did not change
      these results. CONCLUSION: The screening questionnaire is an efficient tool for
      differential inclusion of subjects with and without atopy in epidemiological
      studies.

PMID- 9641573
TI  - Indoor airborne fungal spores, house dampness and associations with environmental
      factors and respiratory health in children.
AB  - BACKGROUND: Children living in a damp house are more likely to suffer from
      respiratory symptoms and it has been suggested that exposure to fungi is an
      important contributing factor. However, more knowledge about underlying
      mechanisms for the association are needed. OBJECTIVE: To identify associations
      between measures of house dampness, levels of airborne fungal spores, housing
      factors and health outcomes in children. METHODS: Eighty households with 148
      children between 7 and 14 years of age were recruited in the Latrobe Valley,
      Victoria, Australia. Some 36% of participating children were asthmatic. Six
      sampling visits were made to each house between March 1994 and February 1995 on a
      2-monthly cycle. Samples for airborne total and viable fungal spores were
      collected from bedrooms, living rooms, kitchens and outdoors. A detailed dwelling
      characterization, using a questionnaire and inspection surveys, was carried out.
      Skin-prick tests were performed with extracts of common aeroallergens and a
      respiratory questionnaire was completed for each child. RESULTS: Large airborne
      fungal spore concentrations were recorded in association with: musty odour, water
      intrusion, high indoor humidity, limited ventilation through open windows, few
      extractor fans and failure to remove indoor mould growth. Visible mould growth or
      condensation evidence was associated with large concentrations of Cladosporium
      spores, but not with large total spore concentrations. Penicillium exposure was a
      risk factor for asthma, while Aspergillus exposure was a risk factor for atopy.
      Fungal allergies were more common among children exposed to Cladosporium or
      Penicillium in winter or to musty odour. Respiratory symptoms were marginally
      more common with exposure to Cladosporium or total spores in winter. CONCLUSION:
      Indoor exposure to certain fungal genera in winter was a risk factor for asthma,
      atopy and respiratory symptoms in children. On the other hand, no significant
      associations were seen between average viable or total spore concentrations and
      child health. Actual measurements of fungal spores predict health outcomes better
      than reported dampness.

PMID- 9641574
TI  - Acoustic rhinometry, rhinomanometry and the amount of nasal secretion in the
      clinical monitoring of the nasal provocation test.
AB  - BACKGROUND: The reliable interpretation of the nasal provocation test in allergy
      diagnosis requires objective and measurable monitoring parameters for clinical
      practice. The clinical usefulness of the nasal provocation test has been limited
      by scanty knowledge of the specificity and sensitivity of the test and a lack of
      reference values. OBJECTIVE: To test and compare three objective monitoring
      parameters of a nasal provocation test in occupational allergic rhinitis. To
      evaluate the magnitude of the nasonasal effects in a unilateral allergen
      challenge. METHODS: The monitoring parameters of the nasal reaction were derived
      from the minimum cross-sectional area on acoustic rhinometry, the nasal
      resistance on active anterior rhinomanometry and the amount of nasal secretion
      measured at 15 min intervals for 60 min. Twenty-three bovine-allergic dairy and
      beef cattle farmers and 19 exposed, non-allergic control subjects were challenged
      first with a control solution and then with the cow allergen. RESULTS: All the
      three monitoring parameters showed high specificity and sensitivity in finding
      allergic and non-allergic subjects. The secretion parameter was found to be
      slightly superior to the acoustic rhinometry and rhinomanometry parameters. The
      side difference in the nasal response between the allergen-challenged and the
      contralateral diluent-challenged cavity was significant for all the parameters
      among the allergic subjects. The contralateral secretion amount was 1/3 of the
      ipsilateral secretion, indicating the magnitude of the contralateral nasonasal
      reflex. A nasonasal reflex was also noted in the nasal patency monitoring. The
      coefficient of variation was significantly lower for the acoustic rhinometry than
      for the rhinomanometry (P=0.0001). The optimal threshold values for a positive
      test were a secretion amount of 100 mg, a 15% decrease in the minimum cross
      sectional area and a 50% increase in the resistance for the observation period of
      30 min and correspondingly 210 mg, 30% and 100% for 60 min. CONCLUSION: The low
      pressure aspiration of the nasal secretion from the anterior part of the nasal
      cavity was found to be a reliable and practical monitoring parameter to be used
      together with acoustic rhinometry or rhinomanometry in the nasal provocation test
      for clinical purposes. Although significant nasonasal effects took place in the
      unilateral allergen challenge, the response was more prominent in the allergen
      challenged than in the contralateral diluent-challenged nasal cavity in most
      allergic subjects.

PMID- 9641575
TI  - Inhalant allergy to egg yolk and egg white proteins.
AB  - BACKGROUND: Several egg white and egg yolk and avian proteins have been described
      as a cause of inhalant allergy. Sometimes inhalational type I hypersensitivity to
      these proteins is associated with food allergy to egg. OBJECTIVE: We studied two
      patients who experienced respiratory and food allergic symptoms upon exposure to
      egg or avian antigens through the inhalative or digestive routes. Clinical and
      immunological studies were carried out in order to identify individual allergens
      from these sources that could be responsible for crossreactivity reactions.
      RESULTS: Patient 1 showed IgE sensitization to egg yolk livetins, feathers, and
      chicken serum. Specific bronchial challenge with chicken albumin and livetin
      extracts elicited a positive early asthmatic response and an increase in serum
      eosinophil cationic protein. Immunoblot and CAP-inhibition studies in this
      patient supported that chicken albumin (alpha-livetin) was the crossreactive
      antigen present in egg yolk and chicken serum and feathers. Patient 2 showed
      sensitization to egg white, ovomucoid and lysozyme. However, SDS-PAGE and
      immunoblot studies demonstrated contaminating lysozyme in the ovomucoid extract
      and identified lysozyme as the main allergen causing egg sensitization in this
      patient. Conjunctival challenge test confirmed allergy to lysozyme. CONCLUSION:
      Egg yolk and egg white proteins may act not only as ingested allergens but also
      as aeroallergens. Immunological studies using highly purified preparations of egg
      proteins are useful for the accurate diagnosis of allergic reactions to egg
      proteins and to identify individual allergens that may be responsible for
      crossreactivity reactions.

PMID- 9641576
TI  - Stability of Pityrosporum ovale allergens during storage.
AB  - BACKGROUND: Pityrosporum ovale is a common saprophyte on the skin capable to
      induce IgE antibody production in atopic dermatitis. Generally IgE response to P.
      ovale has been established with skin-prick test, but the stability of P. ovale
      skin test allergens is not known. OBJECTIVE AND METHODS: In this study we
      analysed the stability of identified allergens of P. ovale in skin test solutions
      during storage. The stability was checked with immunoblotting and densitometry
      after different time periods and at various temperatures. RESULTS: Coomassie
      Brilliant blue staining clearly showed, that proteins were preserved poorly at +
      20 degrees C in 50% glycerol. Even extracts stored at + 4 degrees C during 6 and
      12 months in 50% glycerol were degraded. Only extract stored at + 4 degrees C for
      1 month in 50% glycerol was quite well preserved. According to densitometry
      results the 9 kDa band was the most stable main protein allergen. The 20 kDa and
      especially the 96 kDa bands were far more labile. The stability of low molecular
      allergens was in general better than the stability of high molecular weight
      allergens. CONCLUSIONS: The stability of P. ovale extracts stored for more than 1
      month was poor even when kept at + 4 degrees C temperature. Reliability of
      negative skin prick results should be questioned when older extracts are used. In
      skin test negative cases, the sensitization should be evaluated also with the
      measurement of specific serum IgE antibodies to P. ovale.

PMID- 9641577
TI  - Increased interleukin-6 production during the acute phase of the syndrome of
      episodic angioedema and hypereosinophilia.
AB  - BACKGROUND: The Gleich syndrome is rare and associates recurrent angioedema,
      urticaria, fever, weight gain and blood hypereosinophilia, underlying systemic
      and local inflammation. The pathogenesis of those symptoms remains unclear.
      OBJECTIVE: We wanted to address the possible implication of Interleukin-6 (IL-6)
      in the development of those clinical features, and to identify the cells involved
      in its production. METHODS: A 26-year-old man suffering of this disease was
      referred in hospital. During an acute attack with weight gain, fever and a
      diffuse oedema, a marked increase in eosinophils count (42700/mm3 was observed.
      Serum ECP was elevated at 47 microg/L (normal less than 16). Corticosteroid
      therapy administrated on the 7th day was followed by a rapid remission. Blood
      samples were collected (before, during the attack and under corticosteroid
      therapy) for measurements of serum IL-6 (ELISA, Immunotech, Marseille, France)
      and plasma histamine (RIA, Immunotech, Marseille, France). Blood monocytes and
      eosinophils were isolated and a skin biopsy was performed during the attack.
      RESULTS: The plasma histamine level was within normal range. The level of IL-6 in
      sera peaked to 74 pg/mL, concomitant with the peak of eosinophilia at the acute
      phase phase of the attack. Under corticosteroids, we observed a drop in the IL-6
      serum level to 29 pg/mL, concomitant with the clinical remission. During the
      attack, an increase in IL-6 production was observed in 24 h blood monocyte
      supernatants (11.10(3) pg/mL compared with 2.4+/-0.8.10(3) pg/mL for BM from
      controls) as well as in skin endothelial cells but not in the blood and skin
      eosinophils. In vitro, when endothelial cells were incubated in eosinophils
      supernatants of the patient, liberation of IL-6 was observed (3.3 10(3) pg/mL
      compared with controls: 2.1 10(3) pg/mL) CONCLUSION: Serum IL-6 elevation may be
      related to an increased production by blood monocytes and endothelial cells,
      possibly stimulated by eosinophil mediator during the acute phase of the disease,
      and might participate in the inflammatory reaction of this syndrome.

PMID- 9641579
TI  - Mechanisms of acute eosinophilic inflammation in a case of acute eosinophilic
      pneumonia in a 14-year-old girl.
AB  - BACKGROUND: Acute eosinophilic pneumonia (AEP) is characterized by respiratory
      distress, eosinophilic infiltration in the lung, acute onset, resolution of
      symptoms with corticosteroids and the absence of relapse. Studies to identify the
      pathophysiology of AEP in adults have demonstrated eosinophil activation in the
      BAL fluid, and the presence of high levels of interleukin 5 (IL-5) in the BAL.
      OBJECTIVE: To investigate the pathophysiology of AEP with pleural effusion in a
      paediatric patient. METHODS: ECP levels in the BALand pleural fluid was
      determined by radioimmunoassay. IL-5 and GM-CSF concentrations in the BAL and
      pleural fluid were measured by Elisa. Immunohistochemistry studies performed on
      open lung biopsy included a specific ICAM-1 immunostaining and a ECP specific
      immunostaining (EG2+). RESULTS: High levels of ECP were found in the BAL (5
      microg/L) and pleural fluid (750 microg/L) demonstrating eosinophil activation at
      these sites. Immunohistochemistry illustrated activated (EG2+) eosinophils in the
      interalveolar septa and alveolar space and detected increased expression of ICAM
      1 on alveolar epithelial cells. High levels of IL-5 were measured in the BAL
      (1334 pg/mL) and pleural fluid (7014 pg/mL), while elevated concentrations of GM
      CSF (150 pg/mL) were found in the BAL. CONCLUSION: We conclude that in this
      paediatric patient with AEP activated eosinophils were present in the BAL fluid,
      in the interalveolar septa and in the pleural space while increased ICAM-1
      expression was detected on alveolar epithelial cells, contributing, at least
      partly, for their adhesive interactions. IL-5 and GM-CSF are likely important to
      the massive eosinophil recruitment and activation in the lung, while IL-5 is
      probably related to eosinophil accumulation and activation in the pleural space.
      Thus, lung generation of eosinophil-active cytokines is central to the
      pathophysiology of AEP in paediatric patients.

PMID- 9641578
TI  - Mite antigen-induced IL-4 and IL-13 production by basophils derived from atopic
      asthma patients.
AB  - BACKGROUND: There is increasing evidence for the role of basophils in the
      pathogenesis of atopic diseases such as bronchial asthma, atopic dermatitis and
      atopic rhinitis. Recently, it has been reported that basophils derived from
      healthy donors produce the immunoregulatory cytokines interleukin (IL)-4 and IL
      13 after cross-linking of cell surface IgE. In addition to well-known
      inflammatory mediators, such as histamine and leukotriene C4. these cytokines
      produced by basophils are also considered to be associated with atopic diseases.
      OBJECTIVE: Our first objective was to determine whether or not mite-sensitive
      atopic asthmatic basophils produce IL-4 and IL-13 in response to mite antigens.
      Our second objective was to investigate the relationship between antigen-specific
      or nonspecific IgE in the serum and the production of these cytokines in order to
      determine the association of basophil-derived cytokines with the pathogenesis of
      atopic asthma. Our final objective was to study how production of these cytokines
      could be regulated by some anti-asthma drugs. METHODS: Basophils were purified
      from peripheral venous blood of 67 atopic asthma patients with elevated RAST for
      the house dust mite. Cells were stimulated with mite antigens for 6 hours and
      then IL-4 and IL-13 levels in the supernatants were measured by enzyme-linked
      immunosorbent assay (ELISA). RESULTS: Mite-sensitive asthmatic basophils produced
      IL-4 and IL-13 when stimulated with mite antigens. Mite-induced IL-4 production
      peaked at 6 hours after the stimulation. whereas IL-13 production continued up to
      24 hours. The higher the concentration of mite-specific IgE but not total IgE
      released in the serum, the more IL-4 and IL-13 were produced by basophils in
      response to mite antigens. The production of these cytokines was significantly
      suppressed by the anti-asthma drugs theophylline (IL-4, p<0.001, n=6; IL-13,
      p<0.001, n=10) and dexamethasone (IL-4, p<0.001, n=15; IL-13, p<0.001, n=10).
      CONCLUSION: Mite-antigen-induced IL-4 and IL-13 production by basophils derived
      from mite-sensitive asthma patients was associated with the concentration of mite
      specific IgE and may play an important role in the pathogenesis of atopic asthma.
      The inhibitory effect of dexamethasone and theophylline on allergic inflammation
      may be due to the inhibition of IL-4 and IL-13 production not only by T cells but
      also by basophils.

PMID- 9641580
TI  - Anaphylactic reactions associated with trimethoprim.
AB  - BACKGROUND: Anaphylactic reactions to cotrimoxazole are often ascribed to the
      sulphamethoxazole component of this antibacterial drug. OBJECTIVE: To determine
      whether the trimethoprim component can be the cause of an anaphylactic reaction.
      METHODS: An analysis was made of reports on anaphylaxis attributed to
      trimethoprim, as notified to the Drug Safety Unit of the Dutch Inspectorate for
      Health Care. RESULTS: In the period between September 1981 and November 1995, 13
      such reports were received. Nine were classified as probable anaphylaxis. Of
      these, the causal relationship between exposure to trimethoprim and anaphylaxis
      was classified as definite in three reports, and as probable in the other six.
      The remaining four reports were classified as possible anaphylaxis. In one of
      these, the causal relationship was classified as definite, and in three as
      probable. CONCLUSION: Although anaphylaxis due to trimethoprim seems to be rare,
      it may be more common than previously thought. Apparently, anaphylaxis to
      cotrimoxazole is not always caused by sulphamethoxazole.

PMID- 9641582
TI  - Symptoms and objective measures to define the asthma phenotype.

PMID- 9641581
TI  - PDE4 inhibition and a corticosteroid in chronically antigen exposed conscious
      guinea-pigs.
AB  - BACKGROUND: The physiological and pharmacological consequences of repeated aero
      allergen challenge have not been previously characterized in conscious,
      sensitized guinea-pigs. OBJECTIVES: This study was undertaken to compare the
      effects of two anti-inflammatory compounds, dexamethasone and Ro 20- 1724, on an
      acute and chronic airway inflammation, in terms of airway function, reactivity
      and leucocyte infiltration. METHODS: Sensitized guinea-pigs received eight saline
      or ovalbumin (OvA) inhalation exposures over 4 weeks and either vehicle, the type
      4 PDE inhibitor, Ro 20-1724 (3 mgkg(-1)), or dexamethasone (1.5 mg/kg(-1)), 30
      min before and 6 h after each challenge. Airway function of the conscious animal
      (sGaw) was monitored over the duration of the first and final OvA challenge.
      Airway reactivity to the thromboxane mimetic, U46619, was also determined
      following the final OvA exposure as was the leucocyte infiltration. RESULTS: The
      first antigen challenge induced a large early (0-3h) and smaller late (17-24h)
      bronchoconstrictor response. Neither phase was affected by the drug treatments.
      The final OvA challenge induced early and late phase bronchoconstrictor responses
      but of similar magnitude. The late phase was also significantly prolonged. Ro 20
      1724 and dexamethasone significantly attenuated both phases. Airway reactivity to
      the inhaled thromboxane mimetic, U46619, was also significantly enhanced at 120h
      after the final OvA exposure in contrast to the saline challenged group. This
      hyperreactivity was attenuated by Ro 20-1724 and dexamethasone. Bronchoalveolar
      lavage after repeated OvA exposures revealed eosinophilia which was attenuated by
      Ro 20-1724 and dexamethasone. CONCLUSIONS: This model demonstrates differential
      airway responses to acute and chronic antigen challenge. Repeated administration
      of dexamethasone and Ro 20-1724 with each OvA exposure attenuated all of the
      chronic inflammatory responses: early and late phase responses, hyperreactivity
      and eosinophilia.

PMID- 9641583
TI  - The video questionnaire: one approach to the identification of the asthmatic
      phenotype.

PMID- 9641584
TI  - Methods to assess and quantify BHR (bronchial hyperresponsiveness) in
      epidemiological studies.

PMID- 9641585
TI  - Problems and progress in measuring methacholine bronchial reactivity.

PMID- 9641586
TI  - Early life markers of atopy and asthma.
AB  - Since early intervention could modulate the natural course of atopic disease, the
      availability of predictive markers is of considerable interest. As long as
      specific genetic markers are not available, early IgE-responses (hen's egg)
      together with a positive family history of atopy can be proposed as highly
      specific and predictive markers, which could define subgroups as potential
      candidates for secondary prevention.

PMID- 9641587
TI  - Phenotype stability in asthma and atopy in childhood.
AB  - The asthma phenotype can be described using a combination of the following:
      symptom type, pattern and severity; markers of atopy; and measurement of
      bronchial responsiveness. Because of the very nature of the disease, symptoms of
      asthma are variable in both the short-and the long-term, and the natural history
      of the disease is such that symptoms in an individual may evolve over time
      through different patterns. Although atopy appears to be a life-long attribute
      resulting from an early life switching to a TH2 immune response, the surrogate
      markers of atopy each are subject to their own time-related determinants and
      patterns of change with age. Bronchial responsiveness in childhood is neither
      specific nor sensitive for asthma, and although showing good short-term
      repeatability, can vary widely when measured over a period of months or years.
      Stimuli for responsiveness testing should be chosen which can be inhaled safely
      in high doses so as to allow an end point to be reached by as many subjects
      within a population as possible, and individuals may have to be tested repeatedly
      over time so as to avoid misclassification.

PMID- 9641588
TI  - Phenotypic heterogeneity in asthma and allergy.

PMID- 9641589
TI  - The relationship of parasites to asthma.

PMID- 9641590
TI  - Phenotyping asthma patients for a gene mapping study in Finland.

PMID- 9641591
TI  - Using genes and environments to define asthma and related phenotypes:
      applications to multivariate data.

PMID- 9641592
TI  - Use of cohorts with extensive longitudinal data in investigating the molecular
      genetics of asthma.
AB  - Recent studies have associated several chromosomal regions and specific
      polymorphisms with asthma, atopy and airway hyperresponsiveness. Most of these
      studies have been cross-sectional which substantially limits their power to
      analyse genotype/phenotype associations. Asthma is a such a highly variable
      condition that future genotype/phenotype studies should use longitudinal data.
      Populations with extensive long-term longitudinal data will facilitate more
      precise definition of phenotype and allow analysis of asthma's natural history.
      Longitudinal information also means that each phenotypic attribute can be
      quantified and considered with respect to age. Collecting longitudinal data
      prospectively would be extremely expensive and take many years. Using existing
      longitudinal data sets would clearly be much quicker and more economical, but
      there are very few suitable data sets to be found. Studying a normal and an
      asthmatic population is ideal and would provide complementary genotype/phenotype
      information. This approach is a logical step to using the genotypic information
      obtained from cross-sectional molecular genetic studies to more critically
      establish the effect of genotype on phenotype.

PMID- 9641594
TI  - The genetics of asthma. Maternal effects in atopic disease.

PMID- 9641593
TI  - Approaches and issues in defining asthma and associated phenotypes map to
      chromosome susceptibility areas in large Minnesota families. The Collaborative
      Study for the Genetics of Asthma (CSGA).
AB  - Evidence for linkage of asthma and its associated phenotypes with susceptibility
      genes on chromosome 12 has been demonstrated in one group of Minnesota families.
      The evidence is strong in affected sib pairs and weakens in analysis of the large
      pedigrees. A second group of families provided little evidence for such linkage.
      A discrepancy has been demonstrated in different families. This may be due to
      several factors, including genetic heterogeneity and gene-gene, or gene
      environmental interaction effects as well as the statistical power of the sample
      population used.

PMID- 9641595
TI  - Definition of asthma: possible approaches in genetic studies.

PMID- 9641596
TI  - Using association studies to test for gene-environment interaction asthma and
      other complex diseases.

PMID- 9641597
TI  - The genetics of asthma. Candidate gene approaches: gene-environmental
      interactions.

PMID- 9641598
TI  - Pharmacogenetics of relevant targets in asthma.

PMID- 9641599
TI  - Analytic options for asthma genetics.
AB  - The analytic methods currently being used for the study of the genetics of asthma
      have primarily focused on the evaluation of linkage by non-parametric methods as
      applied to genome screen data in affected sibling pairs. Complexity in the
      analysis of asthma genetics has been shown to occur at several levels, including
      phenotypic definition (wide vs narrow criteria for asthma, including restriction
      based upon multiple phenotypes) and joint analysis of asthma with associated
      phenotypes. Alternative approaches that purport to treat asthma as a quantitative
      trait (a 'score' or 'index') rather than as a qualitative (asthma, yes or no)
      trait were presented, including the development of a 'Framingham Risk Score' for
      asthma, a selection index, or a propensity score. While each of these
      alternatives have interesting features, issues relating to estimation and
      incorporation in a family structure have yet to be resolved. Nonetheless,
      collection of a standard set of clinical data from multiple studies could be used
      in a score to increase the power of genetic mapping studies for asthma.

PMID- 9641600
TI  - Investigating the asthma phenotype.

PMID- 9641601
TI  - Structure/function variants as candidate genes in asthma: linkage vs. association
      for relevance.

PMID- 9641602
TI  - The genetics of asthma. Implications of association studies in asthma.

PMID- 9641603
TI  - The genetics of asthma. Quantitative scores for asthma and atopy.

PMID- 9641604
TI  - Approaches to fine mapping in asthma.

PMID- 9641605
TI  - The genetics of asthma. Mapping genes for complex traits in founder populations.

PMID- 9641606
TI  - Approaches to meta analysis in genetic disorders.

PMID- 9641607
TI  - Report of the Working Group on phenotype approaches.

PMID- 9641608
TI  - Report of the Working Group on analytical methods.

PMID- 9641609
TI  - Report of the Working Group on functional genetics/molecular approaches to asthma
      genetics.

PMID- 9641610
TI  - Evidence for a leptin-neuropeptide Y axis for the regulation of growth hormone
      secretion in the rat.
AB  - The obese gene (OB) product, leptin, has been shown to exert control on metabolic
      processes such as food intake and body weight homeostasis, possibly through a
      neuropeptide Y (NPY) neurotransmission. More recently, leptin has been shown to
      control several neuroendocrine axes, modulating pituitary hormone secretions in
      function of metabolic conditions. Since in the rat growth hormone (GH) secretion
      is dependent upon prevailing metabolic conditions, and NPY has been shown to be
      implicated in the feedback mechanisms of this hormone, we reasoned that leptin
      could also exert control over GH secretion and we examined this hypothesis in
      male rats submitted to a 3-day fast. Circulating leptin concentrations measured
      by RIA abruptly fell to low values after 24 h of fasting and remained low
      thereafter. Upon refeeding, leptin secretion regularly increased. As shown by
      others, pulsatile GH secretion had disappeared after 3 days of fasting. Centrally
      administered leptin (10 microg/day, i.c.v. infusion initiated at the beginning of
      the fasting period) totally prevented the disappearance of pulsatile GH
      secretion. No leak of centrally administered leptin to the general circulation
      was observed. Infusing the same amount of leptin intracerebroventricularly to
      rats receiving ad libitum feeding produced a severe reduction in food intake but
      maintained a normal GH secretory pattern. In contrast, pair-fed rats, submitted
      to the same food restriction, exhibited a marked reduction in GH secretion.
      Hypothalamic NPY gene expression, estimated by Northern blot analysis, was
      significantly increased in fasting rats, and decreased in leptin-treated, fasting
      rats. In rats receiving ad libitum feeding, leptin treatment reduced NPY gene
      expression, consistent with the observed reduction in food intake, whereas pair
      fed animals logically exhibited increased NPY gene expression. In both situations
      with reduced feeding, normal GH secretion was seen in leptin-treated animals
      exhibiting low NPY gene expression, whereas decreased or abolished GH secretion
      was seen in animals not receiving leptin and exhibiting increased NPY mRNA
      levels. Interestingly, despite maintenance of normal GH secretion in leptin
      treated, fasting rats, plasma IGF-I levels were low, as in vehicle-treated rats.
      Indeed, hepatic gene expression for both GH receptor and IGF-I was markedly
      reduced by fasting, and no correction was seen with leptin treatment. In summary,
      the regulation of GH secretion, at least the changes linked with malnutrition,
      appears to be dependent upon a leptin signal, perceived centrally, possibly
      related to circulating levels of this new hormone. The present data suggest that
      leptin can rescue normal pulsatile GH secretion by preventing the documented
      inhibitory action of NPY on GH secretion.

PMID- 9641611
TI  - Long-term inhibitory effects of somatostatin and insulin-like growth factor 1 on
      growth hormone release by serum-free primary culture of pituitary cells from
      European eel (Anguilla anguilla).
AB  - To investigate the ability of hypothalamic and peripheral factors to directly
      regulate growth hormone (GH) release in a primitive teleost, the European eel
      (Anguilla anguilla L.), we used primary cultures of dispersed pituitary cells.
      When cultured for 12 days in a serum-free medium, pituitary cells continuously
      released large amounts of GH, which exceeded the initial cellular content.
      Somatotropin-release inhibiting hormone (SRIH-14) dose-dependently inhibited GH
      release (EC50 0.75 nM) up to a maximal inhibitory effect of 95%. No
      desensitization of somatotropes to SRIH was observed over the 12 days of culture.
      Use of receptor subtype-selective SRIH agonists suggests the existence on eel
      somatotropes of SRIH receptor(s) related to the mammalian sst2/sst3/sst5 class
      rather than to the sst1/sst4 class. Insulin-like growth factor 1 (IGF1) dose
      dependently inhibited GH release (EC50 0.03 nM) up to a maximal inhibitory effect
      of 85%, without desensitization. IGF1 and IGF2 were equipotent in inhibiting GH
      release, whereas insulin was 1,000 times less active, suggesting the implication
      of a receptor related to the mammalian IGF type 1 receptor. These results
      indicate that eel somatotropes are active in vitro without any specific
      additional factors, and suggest the existence of a dominant inhibitory control of
      GH release in vivo. Two potential candidates for this chronic negative regulation
      are a neurohormone, SRIH and a circulating factor, IGF1. These data underline the
      early evolutionary origin of the molecular and functional SRIH-GH-IGF1
      neuroendocrine axis in vertebrates.

PMID- 9641612
TI  - Effects of dexamethasone and alprazolam, a benzodiazepine, on the stimulatory
      effect of hexarelin, a synthetic GHRP, on ACTH, cortisol and GH secretion in
      humans.
AB  - Hexarelin (HEX) is a synthetic GHRP which acts on specific receptors at both the
      pituitary and the hypothalamic level to stimulate GH release both in animals and
      in humans. Like other GHRPs, HEX possesses also acute ACTH and cortisol-releasing
      activity similar to that of hCRH. The mechanisms underlying the stimulatory
      effect of GHRPs on hypothalamo-pituitary-adrenal (HPA) axis are still unclear,
      although a CNS-mediated action has been demonstrated. In 6 normal healthy young
      women (26-34 years) we studied the effects on ACTH and cortisol secretion of HEX
      (2.0 microg/kg i.v. at 0 min) alone and preceded by dexamethasone (DEXA, 1 mg
      p.o. at 23.00 h on the previous night) or alprazolam (ALP, 0.02 mg/kg p.o. at -90
      min), a benzodiazepine which binds to GABA receptors and possesses CRH-mediated
      inhibitory activity on HPA axis. ACTH and cortisol secretion after saline
      administration as well as the GH response to HEX alone and preceded by DEXA or
      ALP were also studied. HEX administration elicited an increase in ACTH (peak vs.
      baseline, mean +/- SEM: 28.0 +/- 6.7 vs. 11.7 +/- 2.2 pg/ml, p < 0.05) and
      cortisol secretion (162.6 +/- 15.0 vs. 137.7 +/- 12.6 microg/l, p < 0.05). DEXA
      pretreatment strongly inhibited basal ACTH (3.2 +/- 0.7 pg/ml, p < 0.01) and
      cortisol levels (11.3 +/- 2.5 microg/l, p < 0.001) and abolished the ACTH and
      cortisol responses to HEX (3.6 +/- 0.9 pg/ml, p < 0.01 and 10.7 +/- 2.0 microg/l,
      p < 0.001), respectively. On the other hand, ALP pretreatment did not
      significantly modify basal ACTH (7.9 +/- 2.0 pg/ml) and cortisol levels (127.6 +/
      14.5 microg/l) but abolished the HEX-induced ACTH and cortisol secretions (8.6
      +/- 2.4 pg/ml, p < 0.05 and 111.0 +/- 6.0 microg/l, p < 0.05), respectively. ACTH
      and cortisol levels after HEX when preceded by ALP overlapped with those recorded
      during saline. HEX induced a clear GH response (peak at 15 min vs. baseline: 65.5
      +/- 20.5 vs. 2.2 +/- 0.7 microg/l, p < 0.03) which was blunted by ALP (peak at 15
      min: 21.5 +/- 5.5 microg/l, p < 0.05) while it was not modified by DEXA
      pretreatment (78.7 +/- 7.6 microg/l). In conclusion, our present data demonstrate
      that the ACTH- and cortisol-releasing effect of HEX is abolished by either
      dexamethasone or alprazolam, a benzodiazepine, which is even able to blunt the GH
      releasing activity of the hexapeptide. These findings suggest that, in
      physiological conditions, the stimulatory effect of GHRPs on HPA axis is
      sensitive to the negative glucocorticoid feedback and could be mediated by
      GABAergic mechanisms; the latter seem also involved in the GH-releasing activity
      of GHRPs.

PMID- 9641613
TI  - Growth hormone, fatigue, poor sleep, and disability in HIV infection.
AB  - Poor sleep, daytime fatigue, and loss of cognitive ability exist during all
      stages of HIV infection, worsening with disease progression. These symptoms
      contribute to disability and poor quality of life. Data from several research
      groups support a role of somnogenic inflammatory process peptides elevated in HIV
      infection, e.g. TNF alpha. Though the literature is in conflict regarding an
      effect of HIV infection on growth hormone (GH) secretion, GH axis dysregulation
      and treatment with GH may be important in HIV infection, e.g. in the wasting
      syndrome. It has long been known that GH varies with changes in sleep. The
      hypothesis tested in the current study was that the relationship between delta
      frequency (0.5-4.0 Hz) sleep EEG amplitude (square root of power from frequency
      analysis) and GH secretion would differ between HIV positive (HIV+) and HIV
      negative (HIV-) subjects. In 14 subjects (6 HIV+ and 8 HIV-, none with current or
      past AIDS-defining illness) a linear relationship change across the night's sleep
      was found in the coupling between delta frequency sleep EEG amplitude and GH
      secretion. The phase coupling change was in opposite directions in HIV+ versus
      HIV- subjects. This difference supports the hypothesis that the brain-based
      coordination of sleep and sleep-related physiology deteriorates early in HIV
      infection, and that GH dysregulation may contribute to this sleep pathology.

PMID- 9641614
TI  - Dehydration-induced renin secretion: involvement of histaminergic neurons.
AB  - Renin secretion is controlled locally in the kidneys as well as via central
      neuronal mechanisms. The neuronal mechanisms are not fully understood but may
      involve the neurotransmitter histamine (HA) since centrally infused HA stimulates
      renin secretion. This, however, does not prove that HA is of any physiological
      importance for the regulation of renin secretion. Dehydration is a physiological
      stimulus of renin secretion and, therefore, we studied the possible role of
      hypothalamic histaminergic neurons in dehydration-induced renin secretion in
      conscious male rats. In addition, we expanded on our previous investigations of
      HA-induced renin secretion. Twenty-four hours of dehydration induced a 3-fold
      increase in plasma renin activity (PRA). Pretreatment with the HA synthesis
      inhibitor alpha-fluoromethylhistidine inhibited the dehydration-induced PRA
      secretion by 80% whereas pretreatment with the H1 receptor antagonist mepyramine
      (MEP) or the H2 receptor antagonist ranitidine (RAN) inhibited the PRA response
      to dehydration by approximately 40%. In euhydrated control rats, none of the HA
      blocking agents had any significant effect on basal PRA secretion. Central
      administration of HA stimulated PRA almost 2-fold and the maximum concentration
      of PRA was reached after 15 min. Pretreatment with the H1 receptor antagonist MEP
      or the H2 receptor antagonist RAN totally inhibited the HA-induced PRA secretion.
      We conclude that HA activates renin secretion via H1 and H2 receptors and that HA
      seems to be a physiological mediator of dehydration-induced renin secretion via
      activation of H1 and H2 receptors. The effect is probably indirect and may among
      others involve the catecholaminergic and serotonergic systems.

PMID- 9641615
TI  - Selective inhibition of magnocellular vasopressin neurons by hypoosmolality:
      effect on histamine- and stress-induced secretion of adrenocorticotropin and
      prolactin.
AB  - We investigated the effect of selective inhibition of magnocellular arginine
      vasopressin (AVP) and oxytocin neurons on histamine (HA)- and restraint-stress
      induced adrenocorticotropin (ACTH) and prolactin (PRL) secretion in conscious
      male rats. The inhibition of magnocellular neurons was obtained by inducing
      chronic hypoosmolality via continuous exposure of the rats to the AVP V2 receptor
      agonist 1-deamino(8-D-arginine)vasopressin (DDAVP) which was released from
      osmotic pumps implanted subcutaneously. In DDAVP-treated rats, plasma osmolality
      and sodium concentration were 273 mosm/l and 130 mmol/l, respectively. In control
      rats, the corresponding values were 291 mosm/l and 139 mmol/l. HA (270 nmol)
      administered intracerebroventricularly or 5 min of restraint stress stimulated
      ACTH and PRL secretion 4- to 11-fold in normoosmolar rats. In hypoosmolar rats,
      the HA-induced ACTH response was inhibited more than 40% whereas the restraint
      stress-induced ACTH response was unaffected. Conversely, the PRL response to HA
      in hypoosmolar rats was unaffected whereas the PRL response to restraint stress
      was inhibited by 40%. In summary, chronic hypoosmolality inhibits HA-induced ACTH
      and restraint-stress-induced PRL secretion indicating involvement of
      magnocellular AVP in these responses.

PMID- 9641616
TI  - Dopamine produced by the stomach may act as a paracrine/autocrine hormone in the
      rat.
AB  - Dopamine (DA) has been suggested to be a protective factor in the
      gastrointestinal tract but neither a source of DA nor its exact targets of action
      have been identified. In this study, we demonstrate high levels of DA (and DOPA)
      which persist after chemical sympathectomy in the gastric juice of rats.
      Immunostaining and in situ hybridization histochemistry reveal the presence of
      tyrosine hydroxylase (TH), DA transporter and vesicular monamine transporters in
      the acid-producing parietal cells. Like DA, TH enzyme activity remains after
      chemical sympathectomy. We also demonstrate active reuptake and storage of DA
      that indicates a regulated release of this neurohormone from parietal cells. DA
      D1b receptor mRNA is the most abundant DA receptor subtype in gastric and
      duodenal epithelium. Therefore, we suggest that selective DA D1b receptor
      agonists may be useful adjuncts in the treatment of duodenal and gastric ulcers.
      Gastric epithelia possess the hallmarks of functional DA neuroendocrine cells,
      suggesting that DA has an important role in self-protective mechanisms of the
      gastrointestinal tract. These findings should allow elucidation of DA role in
      normal and disease states in the stomach and duodenum.

PMID- 9641617
TI  - Effect of melatonin on 24-hour rhythms of ornithine decarboxylase activity and
      norepinephrine and acetylcholine synthesis in submaxillary lymph nodes and spleen
      of young and aged rats.
AB  - Young (50 days old) and old (18 months old) Sprague-Dawley rats were injected
      with mycobacterial Freund's adjuvant to produce an inflammatory disease of the
      joints and were studied the day before, and on days 6, 12 and 18 after injection.
      At every postinjection interval examined, old rats had significantly lower
      circadian amplitudes of pineal melatonin content. On day 18 of arthritis
      development, decreased levels of pineal melatonin were also seen in young rats. A
      second study, carried out 18 days after the injection of Freund's complete
      adjuvant and after 17 daily injections of 10 or 100 microg of melatonin in the
      evening, indicated that melatonin treatment restored the inflammatory response in
      old rats (assessed plethysmographically in hind paws) to the level found in young
      animals. In young rats, an inflammation-promoting effect of 100 microg melatonin
      could be demonstrated. As a consequence of the immune reaction, submaxillary
      lymph node and splenic ornithine decarboxylase activity (an index of lymph cell
      proliferation) augmented significantly, with acrophases of 24-hour rhythms in the
      afternoon for lymph nodes or in the morning for spleen. Mesor and amplitude of
      ornithine decarboxylase rhythm were lowest in old rats, while melatonin injection
      generally augmented its amplitude. Lymph node and splenic tyrosine hydroxylase
      activity (a presynaptic adrenergic marker) reached maximal values during early
      night hours while maximal values of [3H]acetylcholine synthesis (a presynaptic
      cholinergic marker) occurred during the afternoon in lymph nodes. Amplitude and
      mesor of these rhythms were lowest in old rats, an effect generally counteracted
      by melatonin treatment. The results suggest that inflammation is accompanied by
      an age-dependent, significant depression of pineal melatonin synthesis during
      adjuvant-induced arthritis and a decreased amplitude of the circadian rhythm of
      immune cell proliferation and autonomic activity in lymph nodes and spleen. These
      effects are counteracted by injection of melatonin, mainly in old rats.

PMID- 9641618
TI  - In vivo degradation of a poly(propylene fumarate)/beta-tricalcium phosphate
      injectable composite scaffold.
AB  - This study was designed to investigate the in vivo biodegration and
      biocompatibility of a poly(propylene fumarate) (PPF)-based orthopedic
      biomaterial. The effects of varying the PPF to N-vinyl pyrrolidinone ratio and
      PPF to beta-tricalcium phosphate content were studied. The composite mechanical
      properties and local tissue interactions were analyzed over 12 weeks. An initial
      increase in both compressive modulus and strength was seen for composite
      formulations that incorporated beta-tricalcium phosphate. The samples
      incorporating a higher PPF to N-vinyl pyrrolidinone ratio reached a maximal
      compressive strength of 7.7 MPa and a maximal compressive modulus of 191.4 MPa at
      3 weeks. The lower PPF to N-vinyl pyrrolidinone ratio samples gained a maximum
      compressive strength of 7.5 MPa initially and a compressive modulus of 134.0 MPa
      at 1 week. At 6 weeks, all samples for formulations incorporating beta-tricalcium
      phosphate crumbled upon removal and were not mechanically tested. Samples that
      did not incorporate beta-tricalcium phosphate were very weak and insufficient for
      bone replacement at the 4-day time point and beyond. Tissue interactions resulted
      in a mild inflammatory response at the initial time points and mature fibrous
      encapsulation by 12 weeks.

PMID- 9641619
TI  - Cyclic anhydride ring opening reactions: theory and application.
AB  - The development of a zero net shrinkage dental restorative material based upon a
      polymer-bioactive-glass composite requires a second-phase material that expands.
      This study details the mechanisms of organic cyclic anhydride ring expansion via
      hydrolysis. Six cyclic anhydrides were used to represent potential side groups,
      each of which could be an expanding phase or component. Maleic, 4META,
      tetrahydrophthalic, norbornene, itaconic, and succinic anhydrides were modeled
      using the Austin method (AM1), a semi-empirical molecular orbital method. The
      reaction pathways were determined for the anhydride ring opening reaction to form
      an acid for each case. The activation barriers (Ea) for the ring openings were
      found from the transition state geometries wherein only one imaginary eigen value
      in the vibration spectrum existed (a true saddle point). In each case the
      reaction pathway included the hydrogen bonding of a H2O molecule to the ring,
      weakening of the C-O bridging bonds of the ring, and, finally, the dissociation
      of the H2O, forming two carboxyl groups and opening the ring. The activation for
      the ring openings are +34.3, +36.9, +40.6, +43.1, +45.9, and +47.7 kcal/mol,
      respectively. The volumetric expansion of the anhydrides was estimated based upon
      the dilation of C-O-C atomic distances. The dimensional change was found to be
      24.0%, 24.0%, 19.1%, 20.3%, 20.8%, and 17.9% for the anhydride rings,
      respectively. Finally, it was found that a linear correlation exists between the
      cyclic anhydride C-O asymmetric rocking (as-v) vibration and the activation
      energy (Ea) for hydrolysis to an acid. This may be used as an experimental
      indicator of a cyclic anhydride's activity.

PMID- 9641620
TI  - Characterization of soluble, salt-loaded, degradable PLGA films and their release
      of tetracycline.
AB  - A local drug delivery system has been designed to release tetracycline over a
      period of 30 days from poly (lactide-co-glycolide) films. Incorporation of either
      soluble salt excipients or low molecular weight polymeric species has been found
      to modulate the release kinetics of the system. The following research describes
      the fabrication of the delivery system, monitors tetracycline release from the
      system, and fully characterizes the degradation of the polymer films via scanning
      electron microscopy, gel permeation chromatography, differential scanning
      calorimetry, Fourier-transform infrared spectroscopy, and X-ray diffraction
      techniques. Results show that the modulation via use of salts occurs without
      changing the inherent degradation rate of the system. We suggest that this
      phenomenon may be due to the increased amount of swelling and uptake of buffer by
      the films loaded with soluble salt. Uptake, therefore, may be creating
      microscopic pores that permit further diffusion of tetracycline from the polymer
      matrix as well as allow the free monomers to leave the system, thereby preventing
      autocatalysis within the system.

PMID- 9641621
TI  - Laminin-5 coating enhances epithelial cell attachment, spreading, and
      hemidesmosome assembly on Ti-6A1-4V implant material in vitro.
AB  - Enhancement of epithelial cell attachment to laminin-5-coated titanium alloy (Ti
      6Al-4V) implant material was evaluated in vitro. Protein analysis showed that Ti
      6Al-4V has a high affinity for laminin-5 and adsorbed significantly more laminin
      5 than laminin-1. DNA analysis showed that laminin-5 enhanced attachment of
      normal human epidermal keratinocytes (NHEK) to Ti-6Al-4V significantly more than
      did laminin-1 or uncoated controls. The effect of passivation on laminin-5
      adsorption and activity on Ti-6Al-4V also was evaluated. Passivation had no
      significant effect on the amount of protein adsorbed; however, AFM, ESCA, and ToF
      SIMS analyses suggested that passivation affects the conformation of adsorbed
      laminin-5. Although laminin-5 coating significantly enhanced rapid attachment of
      epithelial cells to both passivated and unpassivated Ti-6Al-4V, surface area
      measurements showed that cells spread on laminin-5-coated passivated Ti-6Al-4V
      covered a significantly larger surface area than cells spread on laminin-5-coated
      unpassivated samples. TEM analysis showed that cells formed significantly more
      hemidesmosomes on the surface of laminin-5 coated passivated than on the surface
      of laminin-5 coated unpassivated titanium alloy. The enhancement of rapid cell
      attachment, spreading, and hemidesmosome assembly on laminin-5-coated passivated
      samples may reflect better integration between epithelial cells and titanium
      alloy and thus may be predictive of long-term implant stability.

PMID- 9641622
TI  - Histomorphometrical and mechanical evaluation of titanium plasma-spray-coated
      implants placed in the cortical bone of goats.
AB  - The aim of this study was to investigate the biological and mechanical response
      of bone to titanium plasma-sprayed implants of different roughnesses. Three types
      of titanium plasma-spray coating were applied to beam-shaped implants: Ti2, Ti3,
      and Ti4, with a Ra of 16.5, 21.4, and 37.9 microm, respectively. An Al2O3 grit
      blasted implant (Ti-un) with a Ra of 4.7 microm was used as a control. In total,
      72 implants were inserted in the tibial cortical bone of nine adult female goats.
      These implants were evaluated histologically and mechanically 3 months after
      implantation. At the end of the experiment, of the 72 inserted implants, two
      implants (one Ti2 and one Ti4) were lost. Histological evaluation of the other
      retrieved implants revealed a uniform bone reaction for all implants. The
      unloaded plasma-spray coatings showed no signs of delamination at the implant
      coating interface. Occasionally, particles of the Ti4 coating broke free and were
      found near the implant. Histomorphometry revealed no difference in bone contact
      for the different implants (P > 0.05). Furthermore, the push-out test showed no
      significant difference (P > 0.05). Linear regression showed no interaction
      between the push-out values and the roughness values (r = 0.5). On the basis of
      these results, it may be concluded that the used surface roughnesses did not lead
      to differences in bone response or mechanical attachment strength in goat
      cortical bone.

PMID- 9641623
TI  - Anticoagulant activity of dextran derivatives.
AB  - Carboxymethyl dextran benzylamide sulfonate/sulfates (CMDBS) are synthetic
      polysaccharides with anticoagulant activity. We synthesized eight different
      highly substituted CMDBS and one CMDSu. We studied both their anticoagulant
      activity and the catalysis of thrombin (T) inhibition by heparin cofactor II
      (HCII) and antithrombin (AT) in the presence of these dextran derivatives
      relative to heparin and dextran sulfate (DXSu). The anticoagulant activity of
      CMDBS was due both to direct thrombin inhibition and to catalysis of thrombin
      inhibition by HCII. The anticoagulant and catalytic activities of CMDBS were
      related mainly to their molecular weight and sulfate content. The interaction of
      the dextran derivatives with thrombin does not involve the active site of the
      enzyme. A kinetic study showed that all the CMDBS exhibited higher affinity for
      thrombin than heparin did but lower affinity than DXSu did, suggesting that the
      benzylamide and sulfate groups potentiate the interaction between the dextran
      derivatives and thrombin. This study shows that the mechanism by which the
      dextran derivatives inhibit thrombin is original and is related to preferential
      interaction with thrombin; this both inhibits the clotting activity of the enzyme
      and increases the reaction rate of thrombin inhibition by HCII.

PMID- 9641624
TI  - A multidirectional motion pin-on-disk wear test method for prosthetic joint
      materials.
AB  - A realistic pin-on-disk wear test method for prosthetic joint materials has been
      developed. The new method, called circularly translating pin-on-disk (CTPOD),
      yields wear rates and wear mechanisms similar to those observed in retrieved
      polyethylene acetabular cups. In the established methods, where a polyethylene
      specimen slides against a unidirectionally rotating, or reciprocating, metallic
      or ceramic counterface, the wear rate typically is two orders of magnitude too
      low. In the present study, also, the reciprocator gave negligible wear. In the
      CTPOD method, considerable wear occurs because the direction of sliding rotates
      relative to the polyethylene pin, hence, the molecular orientation effect of
      polyethylene is avoided.

PMID- 9641625
TI  - Electrical properties of glucose-sensitive hydrogels: swelling and conductivity
      relationships.
AB  - The electrical characteristics of a glucose-sensitive polymeric hydrogel have
      been studied. The hydrogel matrices were prepared by radical polymerization of
      solutions containing 2-hydroxyethyl methacrylate, N,N-dimethyl aminoethyl
      methacrylate, tetraethylene glycol dimethacrylate, ethylene glycol, water, and
      glucose oxidase. The hydrogels displayed faster and higher swelling rates for
      lower levels of a crosslinking agent. Electrical conductivity was found to be a
      sensitive measurement of the state of the swelling. A simple model that relates
      hydrogel swelling and conductivity has been proposed.

PMID- 9641626
TI  - Morphology of chemically crosslinked ultrahigh molecular weight polyethylene.
AB  - Morphological characterization of chemically crosslinked ultrahigh molecular
      weight polyethylene was performed by differential scanning calorimetry and
      scanning electron microscopy. The lamellar thickness of nascent UHMWPE inferred
      from DSC endotherms showed a very broad distribution, which was reduced
      significantly after melting and recrystallizing in DSC. Peroxide crosslinking
      further reduced the lamellar thickness distribution compared to uncrosslinked
      samples. After gamma-irradiation, a slowly cooled peroxide-free sample showed a
      greater increase in lamellar thickness distribution. Examination of the
      morphology of freeze-fractured surfaces by SEM showed that a slowly cooled
      peroxide-free UHMWPE exhibited a rougher fracture while chemically crosslinked
      samples showed a smoother fracture. After compression molding at 300 degrees C
      for 2 h, the grain boundaries between particles disappeared for all UHMWPE
      samples, indicating a complete fusion of the original flakes.

PMID- 9641627
TI  - Carbonate substitution in precipitated hydroxyapatite: an investigation into the
      effects of reaction temperature and bicarbonate ion concentration.
AB  - Carbonate substitution in the apatite crystal lattice can occur in either the
      hydroxyl or the phosphate sites, designated as A or B type, respectively, and
      previous investigations generally have described precipitated carbonate
      hydroxyapatite as being B type on the basis of infra red and X-ray data. This
      paper documents the effects of two precipitation variables, namely temperature
      and bicarbonate ion concentration, on the morphology, phase composition, and
      calcium, phosphorus, and carbon contents of precipitated carbonate
      hydroxyapatite. Variations in both temperature and bicarbonate concentration
      could yield either acicular or spheroidal crystals. X-ray diffraction and infra
      red spectroscopy indicated the presence of carbonate in the A site for low
      carbonate contents (< 4 wt%), and at higher carbonate contents (> 4 wt%), the
      carbonate was located predominantly in the B site. On the basis of these
      observations and chemical analyses, a new AB carbonate substitution mechanism is
      proposed that better describes the experimental data than the B-type models used
      previously.

PMID- 9641628
TI  - Si-Ca-P xerogels and bone morphogenetic protein act synergistically on rat
      stromal marrow cell differentiation in vitro.
AB  - This study describes a novel bioactive xerogel glass as a carrier for bone
      morphogenetic protein (BMP) and the value of this carrier in terms of stimulating
      osteogenic activity of rat stromal marrow cells in vitro. These cells were seeded
      onto the surface of xerogel glass disks with BMP either incorporated in the
      glass, adsorbed to the surface of the glass, or added to the culture media and
      then compared to cells on glass with no added BMP or to cells on tissue culture
      plastic (TCP) with and without BMP. Cells were cultured for 6 and 10 days and
      examined for total DNA, alkaline phosphatase activity, and osteocalcin and total
      protein production. Stromal cell differentiation, as measured by alkaline
      phosphatase activity and osteocalcin synthesis was most increased when the BMP
      was incorporated or adsorbed onto the xerogel glass. Cells on xerogel glass
      without BMP were more differentiated than cells grown on plastic with BMP,
      thereby demonstrating the additive effect of a bioactive substrate and BMP on
      osteoblastic cell differentiation. These data indicate that xerogel glass effects
      differentiation of cells with osteogenic potential and that it can serve as a
      delivery vehicle for BMP.

PMID- 9641629
TI  - Fibronectin adsorption, conformation, and orientation on polystyrene substrates
      studied by radiolabeling, XPS, and ToF SIMS.
AB  - Protein adsorption is widely studied by a variety of techniques, but there still
      is little known about protein orientation and conformation after adsorption. This
      probably is due to the large number of parameters involved, such as the
      characteristics of the surface and the structure of the protein. In this study,
      the adsorption of fibronectin was investigated with three different techniques:
      radiolabeling, X-ray photoelectron spectroscopy (XPS), and time-of-flight
      secondary ion mass spectrometry (ToF SIMS) on polystyrene and oxidized
      polystyrene. The first two techniques have been widely used to study protein
      adsorption, allowing us to determine the amount of protein adsorbed on each
      surface. The ToF SIMS, however, is a technique just emerging for the study of
      protein adsorption. This study confirms its utility since ToF SIMS is found to be
      sensitive to the protein orientation and/or conformation at the surface. Indeed,
      the ToF SIMS peaks characteristic of the protein show differences in their
      reduced intensity between the two substrates. These differences, which are not
      detected by XPS, are attributed to different orientations and/or conformations of
      the protein.

PMID- 9641630
TI  - In vitro cellular responses to bioerodible particles loaded with recombinant
      human bone morphogenetic protein-2.
AB  - Porous 50:50 poly(d,l lactide-co-glycolide) microspheres containing varying
      amounts of "free" recombinant human bone morphogenetic protein-2 (rhBMP-2) were
      evaluated for their ability to induce/enhance expression of osteoblastic
      characteristics by pluripotent mesenchymal cells in vitro. "Free" protein (Fp) is
      defined as protein present on the surface and within the porous matrix of the
      microspheres. Four preparations of bioerodible particles (BEP) were used: blank-
      without rhBMP-2; low Fp--24 microg of free rhBMP-2 per g of particles; medium Fp-
      403 microg/g; and high Fp--884 microg/g. C3H10T1/2 cells (C3H) and bone marrow
      stromal cells (BMC) were cultured with 1 mg of BEP for up to 4 weeks, and cell
      growth and expression of osteogenic responses were determined weekly. For both
      cell types, control cultures (neither BEP nor rhBMP-2) and cultures with blank
      BEP exhibited no or minimal osteoblastic characteristics. Compared to control and
      blank BEP cultures, C3H cells responded to particles having medium and high
      amounts of free rhBMP-2 with increased cell growth and alkaline phosphatase
      activity, but osteocalcin secretion and mineralization were not markedly
      influenced. Low Fp BEP enhanced only the alkaline phosphatase activity of C3H
      cells. In contrast, although growth was not affected, rhBMP-2-loaded BEP
      increased alkaline phosphatase activity, osteocalcin secretion, and
      mineralization in BMC cultures in a dose-dependent manner (i.e., blank < low <
      medium < high Fp).

PMID- 9641631
TI  - An immunoelectron microscopic localization of noncollagenous bone proteins
      (osteocalcin and osteopontin) at the bone-titanium interface of rat tibiae.
AB  - This study was designed to investigate by postembedding immunogold method the
      localization and distribution of osteocalcin (Ocl) and osteopontin (Opn) at the
      bone-titanium interface in rat tibiae 14 and 28 days postimplantation to
      determine which bone proteins are present at this interface. Both proteins were
      widely distributed on the newly formed bone and accumulated predominantly in the
      region of bone close to the titanium, in electron-dense patches in the bone, and
      at the osteocytic lacunae. Collagenous osteoid showed little or no labeling for
      either Ocl or Opn. An amorphous zone (20-50 nm) was interposed between the
      titanium and interfacial slender cells, osteoid, or bone, and was labeled
      strongly for Ocl but only weakly for Opn. Furthermore, a second electron-dense
      layer, the lamina limitans, which faces the titanium, was labeled strongly for
      Opn but weakly for Ocl. Ocl as a marker protein of osteoblasts was sometimes
      found in the granules and vesicles of the interfacial cells and extracellularly
      in their intercellular spaces, close to the titanium. However, Opn was not
      detected in any granules. This is the first report to show that the amorphous
      zone contains large amounts of Ocl and small amounts of Opn, and that bone
      contacts titanium through this Ocl-rich amorphous zone. Furthermore, it is
      suggested that the interfacial cells seem to be osteoblasts, and that Ocl in the
      amorphous zone is produced and secreted by these cells and functions with Opn as
      a regulator of the mineralization front close to the titanium, and as a mediator
      of cell-matrix and matrix-matrix/mineral adhesion along the titanium.

PMID- 9641632
TI  - Surface analysis of human plasma fibronectin adsorbed to commercially pure
      titanium materials.
AB  - Protein binding on metallic implant surfaces, such as titanium, is governed by
      the physico-chemical nature of the metallic surface. Human plasma fibronectin
      (HPF) is an important matrix glycoprotein that mediates cell and protein
      attachment to each other or to the extracellular matrix present during wound
      healing. The objective of this study was to investigate the adsorption of HPF
      onto polished commercially pure titanium (cpTi) by using atomic force microscopy
      (AFM) and electron spectroscopy for chemical analysis (ESCA) and to measure the
      resultant surface contact angle before and after HPF binding. Two types of cpTi
      disks, one highly polished in our laboratory (HSS) and one commercially prepared
      (31), were reacted with HPF solutions of varying concentrations (1 microg/mL-10
      ng/mL). ESCA survey spectra of samples coated with 1 microg/mL of fibronectin
      showed an increase in organic nitrogen and carbon compared with uncoated
      controls. Contact angle measurements of HSS and 31 cpTi disks showed no
      significant difference in average contact angle (36.3 degrees +/- 3.5 and 39.1
      degrees +/- 3.1) despite differences in local root mean square (RMS) surface
      roughness (4.45 +/- 0.46 nm and 22.37 +/- 4.17 nm) as measured by AFM. Images
      obtained by AFM showed that 31 specimens were more irregular, with large parallel
      polishing grooves. Adsorbed HPF appeared in a globular form with an average
      length of 16.5 +/- 1.0 nm, a height of 2.5 +/- 0.5 nm, and a width of 9.6 +/- 1.2
      nm. Fibronectin coating on both HSS and 31 cpTi specimens resulted in a
      significant increase in hydrophobicity compared to uncoated specimens. These
      results indicate the significance of HPF on cpTi and may explain how cpTi
      implants function in situ.

PMID- 9641633
TI  - The aortic valve microstructure: effects of transvalvular pressure.
AB  - We undertook this study to establish a more quantitative understanding of the
      microstructural response of the aortic valve cusp to pressure loading. Fresh
      porcine aortic valves were fixed at transvalvular pressures ranging from 0 mmHg
      to 90 mmHg, and small-angle light scattering (SALS) was used to quantify the
      gross fiber structure of the valve cusps. At all pressures the fiber-preferred
      directions coursed along the circumferential direction. Increasing transvalvular
      pressure induced the greatest changes in fiber alignment between 0 and 1 mmHg,
      with no detectable change past 4 mmHg. When the fibrosa and ventricularis layers
      of the cusps were re-scanned separately, the fibrosa layer revealed a higher
      degree of orientation while the ventricularis was more randomly oriented. The
      degree of fiber orientation for both layers became more similar once the
      transvalvular pressure exceeded 4 mmHg, and the layers were almost
      indistinguishable by 60 mmHg. It is possible that, in addition to retracting the
      aortic cusp during systole, the ventricularis mechanically may contribute to the
      diastolic cuspal stiffness at high transvalvular pressures, which may help to
      prevent over distention of the cusp. Our results suggest a complex, highly
      heterogeneous structural response to transvalvular pressure on a fiber level that
      will have to be duplicated in future bioprosthetic heart valve designs.

PMID- 9641634
TI  - Tissue reactions to bacteria-challenged implantable leads with enhanced infection
      resistance.
AB  - Tissue reactions to implantable pacemaker leads were investigated in an early
      infection model in rabbits. Both standard leads and surface-modified leads were
      used. The surface modification technique was applied to achieve controlled
      release of the antibiotic gentamicin. The insulating polyurethane tubing material
      of the leads was provided with an acrylic acid/acrylamide copolymer surface graft
      and then loaded with gentamicin. Implantation periods varied from day 4, to week
      3 1/2, to week 10. We investigated tissue reactions in the absence of an
      infectious challenge and also the efficacy of surface-modified leads in
      preventing infection after challenge with Staphylococcus aureus was evaluated. It
      was demonstrated that the applied surface modification did not induce adverse
      effects although during early postimplantation an increase in infiltration of
      granulocytes and macrophages and wound fluid and fibrin deposition were observed.
      After bacterial challenge, standard leads were heavily infected at each
      explantation period, denoted by abscesses, cellular debris, and bacterial
      colonies. In contrast, little or no infection was observed, either
      macroscopically or by bacterial cultures, with the surface-modified leads.
      Microscopy showed little evidence of the bacterial challenge, and that primarily
      at day 4. It was concluded that the applied surface modification demonstrated
      enhanced infection resistance and thus represents a sound approach to the battle
      against infectious complications with biomaterials.

PMID- 9641635
TI  - In vitro biocompatibility assessment of a nickel-titanium alloy using electron
      microscopy in situ end-labeling (EM-ISEL).
AB  - Shape memory nickel-titanium (NiTi) alloys are potential candidates for
      biomedical applications. However, their equiatomic composition (50 wt% Ni) is
      controversial, and concerns have been raised about their biocompatibility level
      because of the carcinogenicity potential. The relative in vitro genotoxicity of
      NiTi therefore was evaluated and compared to commercially pure titanium (cpTi),
      316L stainless steel (SS 316L), and positive and negative controls. To do so,
      human peripheral blood lymphocytes were cultured in semiphysiological medium that
      previously had been exposed to the biomaterials. The electron microscopy in situ
      end-labeling (EM-ISEL) assay then was performed in order to provide
      quantification of in vitro chromatin DNA single-stranded breaks (SSBs).
      Chromosomes and nuclei were harvested and exposed to exonuclease III, which
      amplifies DNA lesions at 3' ends of breaks. After random priming, incorporation
      of biotin-dUTP was labeled by immunogold binding, which then was detected using
      electron microscopy. Cellular chromatin exposed to the positive control
      demonstrated a significantly stronger immunogold labeling than when it was
      exposed to NiTi, cpTi, SS 316L extracts, or the untreated control. Moreover, gold
      particle counts, whether in the presence of NiTi, cpTi, or the negative control
      medium, were not statistically different. NiTi genocompatibility therefore
      presents promising prescreening results towards its biocompatibility approval.

PMID- 9641636
TI  - Analysis of in vitro reaction layers formed on Bioglass using thin-film X-ray
      diffraction and ATR-FTIR microspectroscopy.
AB  - Fourier transform infrared spectroscopy and thin-film X-ray diffraction (TF-XRD)
      techniques were used to analyze the inorganic carbonate apatite (CA) layer
      developed on a bioactive glass (45S5 type Bioglass) in an in vitro environment.
      The C-O and P-O vibrational modes appeared on the bioactive glass surface
      following immersion in the simulated body fluid solution. Initially, the C-O and
      P-O peaks increased with immersion time as crystallization of CA phase
      progressed. The TF-XRD confirmed that the deposited layer was apatite,
      crystallographically. Furthermore, evidence of preferred orientation in the 001
      direction was seen, indicated by very strong 002 reflection. With time, the
      crystal growth became more random and the intensity of the 002 reflection
      decreased.

PMID- 9641637
TI  - Application of FT-IR microspectroscopy to the study of an injectable composite
      for bone and dental surgery.
AB  - Hydroxypropylmethylcellulose (HPMC) of high-viscosity grade is used as a ligand
      for a bioactive calcium phosphate ceramic (the filler) in a ready-to-use
      injectable sterilized biomaterial for bone and dental surgery. Application of
      physico-chemical methods such as XPS, NMR, or Raman spectroscopy encounters
      difficulties when used to study such a multiphased material. This paper reports
      on the application of FT-IR microspectroscopy (FT-IRM) for the investigation of
      inorganic and organic phases of the rough composite and separated phases obtained
      by mechanical or chemical extraction methods. A comparison of FT-IRM with the
      conventional KBr pellet method was made and indicates that the macro and micro FT
      IR methods are complementary: the former revealed new chemical groups not
      visualized with the KBr method whereas the latter detected the major compound of
      the blend. FT-IR microspectroscopy was revealed to be a powerful method of
      analysis that is complementary to other existing spectroscopic methods. Moreover,
      it is expected to be a useful tool in the study of biomaterials in biological
      samples.

PMID- 9641638
TI  - Anti-nuclear and anti-histone auto-antibodies in autoimmune disease.

PMID- 9641639
TI  - Efficacy of ursodeoxycholic acid in Japanese patients with type 1 autoimmune
      hepatitis.

PMID- 9641640
TI  - Antipyrine clearance in chronic and neoplastic liver diseases: a study of 518
      patients.
AB  - Antipyrine metabolism is widely used as an index of the drug-metabolizing reserve
      of the liver. It is well known that metabolism of this drug is impaired in
      subjects with acute hepatitis or cirrhosis, but conflicting data have been
      reported regarding patients with chronic postinfectious hepatitis or liver
      cancer. We studied conventional liver-function parameters and antipyrine
      metabolism (antipyrine per o.s. 18 mg/kg) in 518 subjects. One hundred and one
      patients had liver metastases (various primaries). Based on the number and size
      of lesions, the hepatic involvement was considered minimal in 47 and massive in
      54 (groups B1 and B2, respectively). One hundred and two had chronic active
      hepatitis (CAH); 51 patients with histological evidence of fibrosis/early
      cirrhosis and 51 patients were without histological evidence of fibrosis/early
      cirrhosis. Ninety-two had histologically confirmed cirrhosis (group D), and the
      remaining 120 had cirrhosis and hepatocellular carcinoma (group E). The control
      group was composed of 103 subjects with healthy livers (group A). Antipyrine
      clearance (AP Cl) in CAH patients with fibrosis (0.246 +/- 0.98 mL/min per kg)
      was similar to that observed in patients with cirrhosis (0.223 +/- 0.148 mL/min
      per kg), and both values were significantly lower than that found in CAH patients
      without fibrosis (0.406 +/- 0.159 mL/min per kg, P < 0.01). Antipyrine clearance
      in patients with liver metastases (0.426 +/- 0.174 mL/min per kg) was similar to
      that of the healthy group (0.489 +/- 0.210 mL/min per kg). Cirrhotics and
      cirrhotics with hepatocellular carcinoma (HCC) presented similar degrees of
      impairment. Antipyrine clearance was positively correlated with serum albumin (r2
      = 0.10, P = 0.01) and prothrombin time (r2 = 0.129, P < 0.01) in all groups,
      except those with liver metastases. In patients with CAH, the presence of
      fibrosis/cirrhosis is associated with impaired antipyrine metabolism. The lack of
      impairment in groups with liver metastases suggests that the functional hepatic
      reserve is maintained even in the presence of massive neoplastic invasion.

PMID- 9641641
TI  - Case report: A hepatocellular carcinoma metastasis in the distal pancreas.
AB  - Hepatocellular carcinoma is a highly malignant neoplasm. Extrahepatic metastases
      are found in 64% of patients with hepatocellular carcinoma. The lungs, regional
      lymph nodes, kidney, bone marrow and adrenals are common sites of metastases.
      Pancreatic metastases are not common (<5%). A case report of a hepatocellular
      carcinoma with a metastasis in the distal pancreas is presented. A resection of
      the primary tumour and metastasis was carried out with the patient still alive 16
      months after resection. This case illustrates that hepatic resection for
      hepatocellular carcinoma with a single local metastasis can be reasonably
      considered although a cure has not been established.

PMID- 9641642
TI  - Case report: Steatonecrosis in the upper abdomen following transcatheter arterial
      embolization for hepatocellular carcinoma.
AB  - A 66-year-old female with liver cirrhosis was treated by transcatheter arterial
      embolization (TAE) for a small hepatocellular carcinoma. She developed
      steatonecrosis with tenderness which occurred in the upper abdomen after TAE. The
      hepatic falciform artery from the middle hepatic artery was detected by
      arteriography. Necrosis in the upper abdomen was considered to be due to
      ischaemic changes caused by micromaterials for embolization of this artery,
      injuries of hepatic arterial endothelia slowly caused by carcinostatics, and
      chemotoxicity. It was considered that such complication as observed in this
      patient should be taken into consideration when performing TAE.

PMID- 9641643
TI  - Clinical significance of serum auto-antibodies in Chinese patients with chronic
      hepatitis C: negative role of serum viral titre and genotype.
AB  - Positive serum anti-nuclear antibody (ANA) and anti-smooth muscle antibody (SMA)
      have been reported in 10-66% of patients with chronic hepatitis C virus (HCV)
      infection from Western countries. However, the mechanism involved in this
      immunological disorder is still unknown. This study was carried out to evaluate
      the prevalence and clinical significance of positive serum auto-antibodies in
      Chinese patients with chronic hepatitis C and to assess the role of serum HCV-RNA
      titre and HCV genotype in the presence of serum auto-antibodies. Serum ANA, SMA
      and anti-mitochondrial antibody (AMA) were measured in 122 patients with chronic
      hepatitis C. Clinical, biochemical and virological data (serum HCV-RNA titre and
      HCV genotype) were compared between patients with and without serum auto
      antibodies. Fifty-eight (48%) patients were associated with positive serum auto
      antibodies: 42 (34%) positive for ANA, six (5%) positive for SMA, nine (7%)
      positive for both ANA and SMA and one (1%) positive for AMA. Clinical parameters
      (age, sex, blood transfusion history), liver biochemical tests, the presence of
      cryoglobulinaemia or cirrhosis, and the response to interferon treatment were not
      significantly different between patients with and without positive serum auto
      antibodies. Serum HCV-RNA levels and HCV genotypes were also not significantly
      different between the two groups. Logistic regression analysis showed that none
      of the previously mentioned parameters were significant predictors to associate
      with serum auto-antibodies in chronic hepatitis C. We concluded that 48% of
      Chinese patients with chronic hepatitis C were associated with positive serum
      auto-antibodies. Hepatitis C virus genotypes and serum HCV-RNA levels were not
      correlated to the presence of serum auto-antibodies. The clinical significance
      and actual pathogenesis of this phenomenon remain to be clarified.

PMID- 9641644
TI  - Case report: Alanine aminotransferase deficiency detected in a patient with
      chronic hepatitis C.
AB  - We report a case of alanine aminotransferase (ALT) deficiency in a 68-year-old
      Japanese female with chronic hepatitis C. The serum was positive for antibody to
      hepatitis C virus (HCV) and HCV-RNA. Liver biopsy showed histological evidence of
      chronic active hepatitis. The level of serum aspartate aminotransferase (sAST)
      was elevated, but sALT was extremely low. The patient was followed up for her
      serum aminotransferase levels for 1.5 years under the treatment with
      ursodeoxycholic acid. The low sALT level persisted during all the follow-up
      period. The ALT activity in liver tissue was also decreased. Based on these
      findings, ALT deficiency was suspected. sALT activity was also found to be low in
      her two sons. This latter finding suggests the hereditary character of this
      abnormality.

PMID- 9641645
TI  - Characterization of anti-histone antibodies in patients with type 1 autoimmune
      hepatitis.
AB  - We have recently found that antibodies to total histones are common in a group of
      American patients with type 1 autoimmune hepatitis (AIH). In an attempt to
      determine the profile and clinical association of anti-histone antibody (AHA), 45
      Japanese AIH patients were studied for serum isotypic reactivity with individual
      histones (H1, H2A, H2B, H3, H4) by enzyme-linked immunosorbent assay and western
      blotting. The results revealed that 40% of sera had reactivities with at least
      one of individual histones and that the antibodies were detected in all three
      classes of immunoglobulins (IgG, IgM, IgA). Immunoglobulin G type anti-H3 showed
      the dominant reactivity and it characterized 72% of sera with AHA. The titre of
      anti-H3 decreased significantly (P < 0.0075) after steroid therapy and the index
      of decrease for anti-H3 was correlated in individuals with that for serum
      aminotransferase. In general, patients with AHA showed higher serum level of
      alanine aminotransferase (P < 0.05), immunoglobulin G (P < 0.025), and higher
      frequency of A2-DR4 haplotype (53 vs 17%) than their seronegative counterparts.
      However, the titre of AHA was low in this disease condition and histone class
      specific antibodies did not distinguish patients with distinctive clinical
      features, although patients with anti-H3 tended to be younger than those without
      AHA.

PMID- 9641646
TI  - Efficacy of ursodeoxycholic acid in Japanese patients with type 1 autoimmune
      hepatitis.
AB  - Ursodeoxycholic acid (UDCA) has been shown to have beneficial effects on patients
      with primary biliary cirrhosis, suggesting that UDCA has immunomodulating
      effects. We investigated the effect of UDCA in patients with autoimmune hepatitis
      (AIH) which is characterized by immunological abnormalities. Eight patients with
      type 1 AIH were treated with 600 mg of UDCA per day for 2 years. Based on the
      criteria of the International Autoimmune Hepatitis Group, five patients were
      diagnosed as definite and three as probable type 1 AIH. Liver function tests were
      performed every 4 weeks, before and during UDCA therapy and the serum levels of
      anti-nuclear antibodies (ANA), smooth muscle antibodies (SMA), immunoglobulin G
      and gamma globulin were determined every 3 months. The levels of serum aspartate
      aminotransferase and alanine aminotransferase significantly decreased from 154 +/
      24 IU/L and 170 +/- 17 IU/L before UDCA therapy to 31 +/- 3 IU/L and 25 +/- 5
      IU/L (P < 0.001) after 1 year of treatment and 28 +/- 2 IU/L and 23 +/- 4 IU/L (P
      < 0.001) after 2 years of treatment. After 2 years of treatment, the levels of
      serum immunoglobulin G and gamma globulin significantly decreased (P < 0.05) and
      ANA titres (5/8 patients) were reduced and SMA (3/5 patients) became negative.
      Furthermore, hepatic histopathological changes of four patients were assessed
      after 1 year of treatment, and an improvement of intrahepatic inflammation, but
      not fibrosis, was observed. In conclusion, these results suggest that UDCA has a
      beneficial therapeutic effect in patients with type 1 autoimmune hepatitis.

PMID- 9641647
TI  - Cystic fibrosis genotypes and alcoholic pancreatitis.
AB  - Pancreatitis and pancreatic insufficiency are associated with both cystic
      fibrosis and alcoholism. The pathogenesis of alcoholic pancreatitis is unknown,
      but only a minority of alcoholics develop pancreatitis, and it has been suggested
      that a genetic predisposition may play a role in this disease. Two observations
      led to the hypothesis that this genetic predisposition could result from
      mutations in the cystic fibrosis gene. First, the prevalence of cystic fibrosis
      mutations in the Caucasian population (approximately 5%) is similar to the
      prevalence of pancreatitis among heavy drinkers. Second, in both diseases,
      pancreatic duct damage is a prominent feature and has been postulated to be the
      initial site of injury. Therefore, the aim of this study was to determine whether
      an increased frequency of mutations in the cystic fibrosis gene occurs in
      alcoholic pancreatitis. The 15 most common cystic fibrosis mutations in a
      Caucasian community were sought in 24 subjects with alcoholic pancreatitis. None
      were homozygous or heterozygous for these mutations. These findings suggest that
      cystic fibrosis mutations are not a major genetic factor predisposing to
      pancreatic injury in alcoholics.

PMID- 9641648
TI  - Helicobacter pylori colonization does not influence the symptomatic response to
      prokinetic agents in patients with functional dyspepsia.
AB  - Functional dyspepsia (FD) is very common, but the pathogenesis of Helicobacter
      pylori leading to FD is still debated. The aim of this study was first to
      evaluate the impact of H. pylori colonization on the efficacy of Paspertase (a
      metoclopramide plus exogenous enzymes regimen for FD patients) and, second, to
      compare the prevalence of H. pylori infection in FD patients with the general
      population. Seventy-four consecutive FD patients were enrolled undergoing
      Paspertase treatment. The symptomatic response was evaluated according to 1-4
      scales of six main dyspeptic symptoms (i.e. epigastric pain/discomfort, early
      satiety, heartburn, nausea/vomiting, abdominal fullness/bloating, and belching).
      Nine hundred and seventy healthy subjects undergoing a paid physical check-up
      were included to study the status of H. pylori colonization. The demographic data
      and basal symptom scores between 43 H. pylori-positive and 31 H. pylori-negative
      patients were not significantly different. Total and individual symptom scores
      improved significantly after 4 weeks of Paspertase therapy (P < 0.05),
      irrespective of H. pylori infection. The prevalences of H. pylori were very
      similar in FD patients and the general population (58.1 vs 58.0%, NS). In
      conclusion, these observations suggest that H. pylori colonization is not
      significant in FD patients of Taiwan while a short-term prokinetic medication is
      effective for these patients, irrespective of H. pylori status.

PMID- 9641649
TI  - Prevalence of Helicobacter pylori in a representative Anglo-Celtic population of
      urban Melbourne.
AB  - The aims of this study were to assess the prevalence of Helicobacter pylori and
      its relationship with different epidemiological factors in an Anglo-Celtic
      Australian population in the Melbourne urban area. Two hundred and seventy-three
      (120 men and 153 women with a mean age of 55.6 and range of 20 to 80 years) of
      396 eligible subjects randomly sampled from the telephone directory were studied.
      An ELISA technique was used to detect H. pylori immunoglobulin (Ig)G antibody and
      self-administered questionnaires were completed. The overall seroprevalence of H.
      pylori was 38% and increased with age from 18% (20-30 years old) to 53% (over 70
      years; P < 0.0001). The acquisition of H. pylori infection was 1% per year. The
      prevalence of H. pylori was 48% in men and 30% in women (P < 0.01). The frequency
      of H. pylori was also associated with low-income levels and current smoking, but
      was not associated with peptic ulcer disease history. The prevalence of H. pylori
      infection in a representative Australian population was found to be similar to
      other developed countries. The risk factors for H. pylori infection include age,
      male sex, low household income and a smoking habit. No correlation between H.
      pylori status and dyspepsia symptoms were observed.

PMID- 9641650
TI  - Amount of Helicobacter pylori in gastric mucus during anti-H. pylori treatment.
AB  - Helicobacter pylori is present in infected patients not only on the gastric
      epithelial cell surface but also in gastric mucus. We developed a competitive
      polymerase chain reaction (cPCR) method for quantitative measurement of H. pylori
      in gastric mucus. The aim of this study was to determine the number of H. pylori
      in gastric mucus before and after anti-H. pylori treatment. Patients with
      duodenal ulcer were treated with lansoprazole alone (n = 11) or lansoprazole and
      amoxycillin (n = 12). The amount of H. pylori in gastric mucus was measured over
      time by a cPCR assay. Helicobacter pylori infection was also tested for using
      histology, culture, and the rapid urease test (RUT). Although most patients
      treated with lansoprazole alone had become H. pylori-negative by the end of
      treatment when tested by histology, RUT, and culture, a large number of H. pylori
      organisms were found in the gastric mucus at that time by cPCR. These patients
      returned to being H. pylori positive 1 to 12 months later on the basis of
      histology, RUT, and culture. However, cPCR results indicated eradication of H.
      pylori by the end of treatment in eight of the 12 patients treated with
      lansoprazole and amoxicillin, and these patients remained H. pylori negative on
      histology, RUT, culture, and cPCR 1 to 12 months later. Testing for H. pylori in
      gastric mucus is thus useful for precise determination of the success or failure
      of H. pylori eradication therapy.

PMID- 9641651
TI  - Enhanced levels of C-X-C chemokine, human GROalpha, in Helicobacter pylori
      associated gastric disease.
AB  - C-X-C Chemokines play an important role for neutrophil extravasation through
      microvessels. Although the level of interleukin (IL)-8 is known to increase in
      the Helicobacter pylori-infected gastric mucosa, another C-X-C chemokine,
      GROalpha, has not been evaluated in the H. pylori-associated gastric mucosal
      injury. The present study was designed to investigate gastric contents of
      GROalpha in relation to those of IL-8 in the gastric mucosa of H. pylori-infected
      peptic ulcer patients. Thirty-eight patients with gastric ulcer and 41 with
      gastritis underwent endoscopy with informed consent and 49 were found to be H.
      pylori positive and 30 H. pylori negative. Biopsies from the gastric corpus were
      performed in each patient to examine the H. pylori colonization by bacterial
      culture, the rapid urease test and histological specimens as well as measurement
      of the contents of human GROalpha and IL-8. Helicobacter pylori infection was
      eradicated in 21 patients by triple therapy (lansoprazole 30 mg, amoxycillin 2.0
      g, clarithromycin 600 mg; 2 weeks). The samples for GROalpha and IL-8 assay were
      homogenized in 0.02% aprotinin containing phosphate-buffered solution and the
      mucosal contents of GROalpha and IL-8 in the supernatants were quantified by
      sandwich enzyme immunoassay methods. The levels of GROalpha and IL-8 in H. pylori
      positive gastric mucosa were significantly higher than those in the H. pylori
      negative mucosa. There was a significant linear correlation between the levels of
      GROalpha and IL-8 (r = 0.798, P < 0.01). After the eradication of H. pylori by
      the triple therapy, the levels of GROalpha and IL-8 were significantly decreased.
      The GROalpha showed an increase in the H. pylori-positive gastric mucosa in a
      similar fashion as IL-8 contents, suggesting a pathogenetic role for GROalpha in
      H. pylori-associated gastric mucosal injury.

PMID- 9641652
TI  - Tamoxifen inhibits colorectal cancer metastases in the liver: a study in a murine
      model.
AB  - Liver metastases account for over 70% of deaths resulting from colorectal
      carcinoma, with survival rates varying between 6-18 months. At present, surgical
      resection offers the only hope for a cure, while chemotherapy, focal destructive
      techniques and selective internal radiation offer palliative care. Tamoxifen, a
      non-steroidal anti-oestrogen is primarily known for treating oestrogen receptor
      (ER)-positive breast cancer. Some studies suggest that tamoxifen may have
      beneficial effects in malignancies other than breast cancer. These inhibitory
      effects, which have been shown to be independent of the ER, highlight new
      mechanisms of therapeutic action. Using an intrasplenic animal model we report
      the efficacy of tamoxifen on experimental liver metastases. In this model, a
      dimethyl hydrazine-induced colon carcinoma cell suspension is introduced into the
      portal circulation via the spleen, which results in secondary tumour deposits in
      the liver in virtually all animals. Tamoxifen was administered at a dose of 1
      mg/kg suspended in 1.0% methyl cellulose. The control group received an equal
      volume of the vehicle. The reagents were administered s.c. on the day of
      metastases induction and were continued daily over a 4 week period. The effect of
      tamoxifen on tumour growth was assessed by stereology and bromodeoxyuridine
      immunohistochemistry at selected time points. Data were assessed by a multiple
      analysis of variance where P < 0.05 was considered significant. In the control
      group the volume of metastases increased from 44 +/- 41 mm3 at day 10 to 517 +/-
      380 mm3, 1394 +/- 598 mm3 and 2082 +/- 675 mm3 by days 16, 22 and 28,
      respectively. Daily administration of tamoxifen exerted an inhibitory effect on
      tumour growth during the first 3 weeks, recording a volume of 421 +/- 299 mm3 by
      day 22 compared with the control group at that time point (P = 0.00004). The
      inhibitory effect diminished by the fourth week recording a tumour volume of 1344
      +/- 674 mm3 by day 28. Inhibition of tumour growth at day 22 coincides with a
      reduction of cells in the S phase of the cell cycle. The percentage of brdU
      positive nuclear profiles in metastases of tamoxifen-treated mice at 3 weeks was
      35.87 +/- 5.60% compared with 48.01 +/- 3.96% in the control group (P = 0.001).
      These data suggest that tamoxifen has a potent inhibitory action on colorectal
      liver metastases by exerting an effect on cell proliferation.

PMID- 9641653
TI  - What's new in colorectal cancer screening?
AB  - There is now good evidence from case control studies and randomized controlled
      trials that screening average-risk subjects for colorectal cancer using faecal
      occult blood tests reduces mortality. There is limited data indicating that
      screening sigmoidoscopy can also achieve this. There is no evidence yet that
      screening by colonoscopy or double contrast barium enema can reduce mortality.
      Calculations of cost-effectiveness suggest that all of the above strategies
      should be economically worthwhile but there is no convincing evidence to suggest
      that one strategy is markedly more cost-effective than the others. Further data
      on several aspects of screening are required before any decisions are made on
      which form(s) of screening should be offered nationwide.

PMID- 9641654
TI  - Case report: Pneumatosis cystoides intestinalis associated with post-surgical
      bowel anastomosis: a report of three cases and review of the Japanese literature.
AB  - We report three cases of pneumatosis cystoides intestinalis (PCI) occurring in
      association with post-surgical bowel anastomosis. A 74-year-old man, a 58-year
      old woman, and a 62-year-old woman were found to have PCI at the colonic side of
      a bowel anastomosis at 4 years, 3 years and 1 year after operation, respectively,
      for right colon carcinoma, although all were asymptomatic. They all had a
      positive anti-nuclear antibody test and had received postoperative cancer
      chemotherapy. The clinical features of 123 cases of PCI reported in Japan between
      1981 and 1995 were also reviewed. On the basis of the present and previous cases,
      we propose that post-surgical anastomosis, cancer chemotherapy, and
      predisposition to collagen vascular disease might be responsible for the damage
      to intestinal mucosa that leads to the development of PCI.

PMID- 9641655
TI  - Images in gastroenterology. Occult rectal prolapse and solitary rectal ulcer.

PMID- 9641656
TI  - Hepatobiliary and pancreatic imaging. Retroperitoneal mature cystic teratoma with
      a fat ball.

PMID- 9641657
TI  - Chronic hepatitis virus infection in children.
AB  - Hepatitis B and C viruses (HBV and HCV) are the two main hepatitis viruses
      causing chronic liver diseases in children. In hyperendemic areas, nearly half of
      the primary infection in chronic HBV carriers occurs during the perinatal period
      through the transmission from hepatitis B e antigen (HBeAg)-positive mothers. The
      other half are from horizontal transmission mainly through intrafamilial spread
      or injection using unsterilized needles. During the natural course of chronic HBV
      infection, spontaneous HBeAg/anti-HBe seroconversion occurs very rarely (2%
      annually) before 3 years of age. After 3 years of age, the HBeAg seroconversion
      rate increases gradually to 5% per year. Those with mothers who are hepatitis B
      carriers tend to clear HBeAg slower than those whose mothers are non-carriers.
      Transplacental HBeAg may cause T cell tolerance in infected children. Universal
      HBV immunization programmes have been effective in reducing the hepatitis B
      carrier rate more than 10-fold, and the incidence of hepatocellular carcinoma in
      children has also been decreased significantly. Hepatitis C virus infection
      occurs mainly in high-risk children, such as those who received blood products
      (blood diseases, malignancies, post-open heart surgery etc.), children of HCV
      infected mothers, and in hyperendemic areas, from injection using unsterile
      needles. Mother-to-infant transmission occurs on average in 5% of infants of
      viraemic mothers. The maternal HCV-RNA titre is the most important factor
      determining the infectivity. Chronicity developed in 60-80% of HCV-infected
      children. Although transient or persistent elevation of aminotransferases occurs
      frequently in chronically HCV-infected children, liver histology showed minimal
      or mild changes only. The most prevalent genotype of HCV in children is Ib.
      Screening of the blood products for HCV antibody has markedly reduced the rate of
      HCV infection in children at risk. However, vaccine development is needed to
      prevent mother-to-infant transmission and other routes of infections.

PMID- 9641658
TI  - Benefits of federation.

PMID- 9641659
TI  - Call to drop charges in French blood affair.

PMID- 9641660
TI  - US research safety system 'in jeopardy'.

PMID- 9641661
TI  - Job discrimination based on genetics set for California ban.

PMID- 9641662
TI  - Japanese media fuel fears of 'endocrine disrupters'.

PMID- 9641663
TI  - Canada putting its faith in consolidation in health sector.

PMID- 9641664
TI  - Europeans adapt to compete with US neuroscience body.

PMID- 9641665
TI  - Cell biologists set out on the path of reform.

PMID- 9641666
TI  - Avenues of discovery in bioprospecting.

PMID- 9641667
TI  - Avenues of discovery in bioprospecting.

PMID- 9641668
TI  - Cancer controversy.

PMID- 9641669
TI  - No conference critique.

PMID- 9641670
TI  - Congressional hearings on genetics research.

PMID- 9641671
TI  - Circadian rhythms. New cogwheels in the clockworks.

PMID- 9641672
TI  - Molecular motors. Keeping the beat.

PMID- 9641673
TI  - HIV. Envelope's letters boxed into shape.

PMID- 9641674
TI  - Pere Alberch (1954-98)

PMID- 9641675
TI  - Mechanisms for memory types differ.

PMID- 9641676
TI  - Walking on Mars.

PMID- 9641677
TI  - Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor
      and a neutralizing human antibody.
AB  - The entry of human immunodeficiency virus (HIV) into cells requires the
      sequential interaction of the viral exterior envelope glycoprotein, gp120, with
      the CD4 glycoprotein and a chemokine receptor on the cell surface. These
      interactions initiate a fusion of the viral and cellular membranes. Although
      gp120 can elicit virus-neutralizing antibodies, HIV eludes the immune system. We
      have solved the X-ray crystal structure at 2.5 A resolution of an HIV-1 gp120
      core complexed with a two-domain fragment of human CD4 and an antigen-binding
      fragment of a neutralizing antibody that blocks chemokine-receptor binding. The
      structure reveals a cavity-laden CD4-gp120 interface, a conserved binding site
      for the chemokine receptor, evidence for a conformational change upon CD4
      binding, the nature of a CD4-induced antibody epitope, and specific mechanisms
      for immune evasion. Our results provide a framework for understanding the complex
      biology of HIV entry into cells and should guide efforts to intervene.

PMID- 9641678
TI  - A nutrient-sensing pathway regulates leptin gene expression in muscle and fat.
AB  - Leptin, the protein encoded by the obese (ob) gene, is synthesized and released
      in response to increased energy storage in adipose tissue. However, it is still
      not known how incoming energy is sensed and transduced into increased expression
      of the ob gene. The hexosamine biosynthetic pathway is a cellular 'sensor' of
      energy availability and mediates the effects of glucose on the expression of
      several gene products. Here we provide evidence for rapid activation of ob gene
      expression in skeletal muscle by glucosamine. Increased tissue concentrations of
      the end product of the hexosamine biosynthetic pathway, UDP-N-acetylglucosamine
      (UDP-GlcNAc), result in rapid and marked increases in leptin messenger RNA and
      protein levels (although these levels were much lower than those in fat). Plasma
      leptin levels and leptin mRNA and protein levels in adipose tissue also increase.
      Most important, stimulation of leptin synthesis is reproduced by either
      hyperglycaemia or hyperlipidaemia, which also increase tissue levels of UDP-N
      acetylglucosamine in conscious rodents. Finally, incubation of 3T3-L1 pre
      adipocytes and L6 myocytes with glucosamine rapidly induces ob gene expression.
      Our findings are the first evidence of inducible leptin expression in skeletal
      muscle and unveil an important biochemical link between increased availability of
      nutrients and leptin expression.

PMID- 9641679
TI  - Male-to-female sex reversal in M33 mutant mice.
AB  - Polycomb genes in Drosophila maintain the repressed state of homeotic and other
      developmentally regulated genes by mediating changes in higher-order chromatin
      structure. M33, a mouse homologue of Polycomb, was isolated by means of the
      structural similarity of its chromodomain. The fifth exon of M33 contains a
      region of homology shared by Drosophila and Xenopus. In Drosophila, its deletion
      results in the loss of Polycomb function. Here we have disrupted M33 in mice by
      inserting a poly(A) capture-type neo(r) targeting vector into its fifth exon.
      More than half of the resultant M33cterm/M33cterm mutant mice died before
      weaning, and survivors showed male-to-female sex reversal. Formation of genital
      ridges was retarded in both XX and XY M33cterm/M33cterm embryos. Gonadal growth
      defects appeared near the time of expression of the Y-chromosome-specific Sry
      gene, suggesting that M33 deficiency may cause sex reversal by interfering with
      steps upstream of Sry. M33cterm/M33cterm mice may be a valuable model in which to
      test opposing views regarding sex determination.

PMID- 9641680
TI  - Premotor commands encode monocular eye movements.
AB  - Binocular coordination of eye movements is essential for stereopsis (depth
      perception) and to prevent double vision. More than a century ago, Hering and
      Helmholtz debated the neural basis of binocular coordination. Helmholtz believed
      that each eye is controlled independently and that binocular coordination is
      learned. Hering believed that both eyes are innervated by common command signals
      that yoke the eye movements (Hering's law of equal innervation). Here we provide
      evidence that Hering's law is unlikely to be correct. We show that premotor
      neurons in the paramedian pontine reticular formation that were thought to encode
      conjugate velocity commands for saccades (rapid eye movements) actually encode
      monocular commands for either right or left eye saccades. However, 66% of the
      abducens motor neurons, which innervate the ipsilateral lateral rectus muscle,
      fire as a result of movements of either eye. The distribution of sensitivity to
      ipsilateral and contralateral eye movements across the abducens motor neuron pool
      may provide a basis for learning binocular coordination in infancy and adapting
      it throughout life.

PMID- 9641681
TI  - Silent glutamatergic synapses and nociception in mammalian spinal cord.
AB  - Neurons in the superficial dorsal horn of the spinal cord are important for
      conveying sensory information from the periphery to the central nervous system.
      Some synapses between primary afferent fibres and spinal dorsal horn neurons may
      be inefficient or silent. Ineffective sensory transmission could result from a
      small postsynaptic current that fails to depolarize the cell to threshold for an
      action potential or from a cell with a normal postsynaptic current but an
      increased threshold for action potentials. Here we show that some cells in the
      superficial dorsal horn of the lumbar spinal cord have silent synapses: they do
      not respond unless the holding potential is moved from -70 mV to +40 mV.
      Serotonin (5-hydroxytryptamine, 5-HT), an important neurotransmitter of the raphe
      spinal projecting pathway, transforms silent glutamatergic synapses into
      functional ones. Therefore, transformation of silent glutamatergic synapses may
      serve as a cellular mechanism for central plasticity in the spinal cord.

PMID- 9641682
TI  - Synaptic laminin prevents glial entry into the synaptic cleft.
AB  - Presynaptic and postsynaptic membranes directly oppose each other at chemical
      synapses, minimizing the delay in transmitting information across the synaptic
      cleft. Extrasynaptic neuronal surfaces, in contrast, are almost entirely covered
      by processes from glial cells. The exclusion of glial cells from the synaptic
      cleft, and the long-term stability of synapses, presumably result in large part
      from the tight adhesion between presynaptic and postsynaptic elements. Here we
      show that there is another requirement for synaptic maintenance: glial cells of
      the skeletal neuromuscular synapse, Schwann cells, are actively inhibited from
      entering the synaptic cleft between the motor nerve terminal and the muscle
      fibre. One inhibitory component is laminin 11, a heterotrimeric glycoprotein that
      is concentrated in the synaptic cleft. Regulation of an inhibitory interaction
      between glial cells and synaptic cleft components may contribute to synaptic
      rearrangements, and loss of this inhibition may underlie the loss of synapses
      that results from injury to the postsynaptic cell.

PMID- 9641683
TI  - Association of missense and 5'-splice-site mutations in tau with the inherited
      dementia FTDP-17.
AB  - Thirteen families have been described with an autosomal dominantly inherited
      dementia named frontotemporal dementia and parkinsonism linked to chromosome 17
      (FTDP-17), historically termed Pick's disease. Most FTDP-17 cases show neuronal
      and/or glial inclusions that stain positively with antibodies raised against the
      microtubule-associated protein Tau, although the Tau pathology varies
      considerably in both its quantity (or severity) and characteristics. Previous
      studies have mapped the FTDP-17 locus to a 2-centimorgan region on chromosome
      17q21.11; the tau gene also lies within this region. We have now sequenced tau in
      FTDP-17 families and identified three missense mutations (G272V, P301L and R406W)
      and three mutations in the 5' splice site of exon 10. The splice-site mutations
      all destabilize a potential stem-loop structure which is probably involved in
      regulating the alternative splicing of exon10. This causes more frequent usage of
      the 5' splice site and an increased proportion of tau transcripts that include
      exon 10. The increase in exon 10+ messenger RNA will increase the proportion of
      Tau containing four microtubule-binding repeats, which is consistent with the
      neuropathology described in several families with FTDP-17.

PMID- 9641684
TI  - The antigenic structure of the HIV gp120 envelope glycoprotein.
AB  - The human immunodeficiency virus HIV-1 establishes persistent infections in
      humans which lead to acquired immunodeficiency syndrome (AIDS). The HIV-1
      envelope glycoproteins, gp120 and gp41, are assembled into a trimeric complex
      that mediates virus entry into target cells. HIV-1 entry depends on the
      sequential interaction of the gp120 exterior envelope glycoprotein with the
      receptors on the cell, CD4 and members of the chemokine receptor family. The
      gp120 glycoprotein, which can be shed from the envelope complex, elicits both
      virus-neutralizing and non-neutralizing antibodies during natural infection.
      Antibodies that lack neutralizing activity are often directed against the gp120
      regions that are occluded on the assembled trimer and which are exposed only upon
      shedding. Neutralizing antibodies, by contrast, must access the functional
      envelope glycoprotein complex and typically recognize conserved or variable
      epitopes near the receptor-binding regions. Here we describe the spatial
      organization of conserved neutralization epitopes on gp120, using epitope maps in
      conjunction with the X-ray crystal structure of a ternary complex that includes a
      gp120 core, CD4 and a neutralizing antibody. A large fraction of the predicted
      accessible surface of gp120 in the trimer is composed of variable, heavily
      glycosylated core and loop structures that surround the receptor-binding regions.
      Understanding the structural basis for the ability of HIV-1 to evade the humoral
      immune response should assist in the design of a vaccine.

PMID- 9641685
TI  - Dynein arms are oscillating force generators.
AB  - Eukaryotic flagella beat rhythmically. Dynein is a protein that powers flagellar
      motion, and oscillation may be inherent to this protein. Here we determine
      whether oscillation is a property of dynein arms themselves or whether
      oscillation requires an intact axoneme, which is the central core of the
      flagellum and consists of a regular array of microtubules. Using optical trapping
      nanometry, we measured the force generated by a few dynein arms on an isolated
      doublet microtubule. When the dynein arms on the doublet microtubule contact a
      singlet microtubule and are activated by photolysis of caged ATP8, they generate
      a peak force of approximately 6pN and move the singlet microtubule over the
      doublet microtubule in a processive manner. The force and displacement oscillate
      with a peak-to-peak force and amplitude of approximately 2 pN and approximately
      30 nm, respectively. The geometry of the interaction indicates that very few
      (possibly one) dynein arms are needed to generate the oscillation. The maximum
      frequency of the oscillation at 0.75 mM ATP is approximately 70 Hz; this
      frequency decreases as the ATP concentration decreases. A similar oscillatory
      force is also generated by inner dynein arms alone on doublet microtubules that
      are depleted of outer dynein arms. The oscillation of the dynein arm may be a
      basic mechanism underlying flagellar beating.

PMID- 9641686
TI  - Meeting highlights: 47th Annual Scientific Sessions of the American College of
      Cardiology.

PMID- 9641687
TI  - Reactive oxygen species, metalloproteinases, and plaque stability.

PMID- 9641688
TI  - Coronary bypass grafting with bilateral internal thoracic arteries and the right
      gastroepiploic artery.

PMID- 9641689
TI  - International, randomized, controlled trial of lamifiban (a platelet glycoprotein
      IIb/IIIa inhibitor), heparin, or both in unstable angina. The PARAGON
      Investigators. Platelet IIb/IIIa Antagonism for the Reduction of Acute coronary
      syndrome events in a Global Organization Network.
AB  - BACKGROUND: Unstable angina and non-Q-wave myocardial infarction involve coronary
      arterial plaque rupture, platelet activation, and thrombus formation. This study
      tested the benefit of different doses of lamifiban (a platelet IIb/IIIa
      antagonist) alone and in combination with heparin in patients with these
      conditions to select the most promising lamifiban regimen for subsequent
      evaluation. METHODS AND RESULTS: At 273 hospitals in 20 countries, 2282 patients
      were randomly assigned to lamifiban (2x2 factorial design: low-dose [1
      microg/min] with and without heparin versus high-dose [5 microg/min] with and
      without heparin) or to standard therapy (placebo and heparin). All patients
      received aspirin. The composite primary end point of death or nonfatal myocardial
      infarction at 30 days occurred in 11.7% of those receiving standard therapy,
      10.6% receiving low-dose lamifiban, and 12.0% receiving high-dose lamifiban
      (P=0.668). By 6 months, this composite was lowest for those assigned to low-dose
      lamifiban (P=0.027) and intermediate for those assigned to high-dose lamifiban
      (P=0.450) compared with control (13.7%, 16.4%, and 17.9%, respectively). Compared
      with control, the combination of high-dose lamifiban and heparin resulted in more
      intermediate or major bleeding (12.1% versus 5.5%; P=0.002) and a similar rate of
      ischemic events. Conversely, low-dose lamifiban and heparin yielded similar
      bleeding rates as in the control group but fewer ischemic events at 6 months
      (12.6% versus 17.9%; P=0.025). CONCLUSION: In unstable angina and non-Q-wave
      infarction, platelet IIb/IIIa antagonism with lamifiban reduces adverse ischemic
      events at 6 months beyond that of aspirin and heparin therapy. The role of
      conjunctive heparin remains uncertain but appears more favorable with low-dose
      IIb/IIIa antagonism. Larger-scale study is needed to more reliably estimate these
      effects.

PMID- 9641690
TI  - Interlesion dependence of the risk for restenosis in patients with coronary stent
      placement in in multiple lesions.
AB  - BACKGROUND: Little is known about the behavior with regard to restenosis of
      multiple lesions within the same patient treated with intracoronary stenting. Our
      objective was to test the hypothesis that there is an intrapatient dependence of
      restenosis between lesions. METHODS AND RESULTS: Quantitative analysis was
      carried out on angiograms obtained before, immediately after, and at 6 months
      after coronary stent placement in 1734 lesions in 1244 patients. We used a
      specialized logistic regression that not only accounts for intraclass correlation
      but also quantifies it in the form of odds ratio (OR) as the change in risk of a
      lesion to develop restenosis if another companion lesion had restenosis. The
      model was based on 23 patient- and lesion-related variables with binary
      restenosis (diameter stenosis > or =50%) as end point. The overall restenosis
      rate was 27.5%: 24.4% for single-lesion, 28.6% for double-lesion, and 33.8% for >
      or =3-lesion interventions. After adjustment for the influence of significant
      factors (hypercholesterolemia, systemic arterial hypertension, diabetes mellitus,
      previous PTCA, ostial lesion, location in left anterior descending coronary
      artery, number of stents placed, vessel size, stenosis severity, balloon-to
      vessel ratio, and final result), the analysis found a significant intrapatient
      correlation, OR 2.5 (1.8 to 3.6). This means that in patients with multilesion
      interventions, the risk of a lesion to develop restenosis is 2.5 times higher if
      a companion lesion has restenosis, independently of the presence or absence of
      analyzed patient risk factors (eg, diabetes). CONCLUSIONS: This study
      demonstrates that there is a dependence of restenosis between coronary lesions in
      patients who undergo a multilesion intervention. The likelihood of restenosis for
      a lesion is higher when another companion lesion has also developed restenosis.
      Other, as yet unidentified patient factors may be the source of this intrapatient
      correlation of restenosis.

PMID- 9641691
TI  - Low recurrence of angina pectoris after coronary artery bypass graft surgery with
      bilateral internal thoracic and right gastroepiploic arteries.
AB  - BACKGROUND: In the past 10 years, there has been a trend to use more arterial
      grafts instead of vein grafts for coronary artery bypass graft surgery. Although
      there are many reports on the short- and mid-term follow-up of patients who
      underwent arterial revascularization with 1 or 2 arteries, little has been
      reported on the follow-up of patients with 3-vessel disease who received 3
      arteries. METHODS AND RESULTS: We reviewed a group of 256 patients with 3-vessel
      disease who received the right gastroepiploic artery together with both internal
      thoracic arteries (ITAs). Vein grafts were not used in these patients. The
      patients were monitored for up to 7 years (mean, 51+/-15 months). Seven-year
      actuarial survival was 91.1%. The cumulative probability of event-free survival
      for myocardial infarction, reintervention, and angina pectoris at 7 years was
      97.3%, 95.4%, and 85.4%, respectively. CONCLUSIONS: We conclude that concomitant
      use of the gastroepiploic artery with both ITAs results in low mortality and a
      low incidence of myocardial infarction and reintervention at follow-up. Most
      interestingly, we found 85.4% freedom from angina pectoris after 7 years, which
      is considerably lower than the results of studies in which vein grafts, single
      ITA grafts, or double ITA grafts are used. These results strongly support the use
      of both ITAs and the right gastroepiploic artery for bypass grafting in patients
      with 3-vessel disease.

PMID- 9641693
TI  - Sympathetic denervation and reinnervation after arterial switch operation for
      complete transposition.
AB  - BACKGROUND: Sympathetic cardiopulmonary nerves arise from the cervical
      sympathetic trunks and the stellate ganglia and subsequently course along the
      origin of the great arteries and the coronary arteries to innervate the
      ventricles. Therefore, the sympathetic nerves may be obligatorily interrupted by
      the arterial switch operation (ASO) for complete transposition of the great
      arteries. METHODS AND RESULTS: To demonstrate and characterize the possible
      sympathetic denervation, 51 patients after ASO, 4.8 years old (range, 1 month to
      10.1 years), underwent [123I]metaiodobenzylguanidine (MIBG) imaging of the
      sympathetic nerve terminal. MIBG uptake to the heart was graded by quantitative
      analysis using the heart-to-mediastinum (H/M) ratio of MIBG uptake. A
      quantitative criterion for absent uptake of MIBG was set to 1.48 in the H/M
      ratio. Four patients < 1 month after ASO showed complete absence of MIBG uptake,
      which had been observed preoperatively. In contrast, 47 patients late after ASO
      (range, 15 months to 10.1 years) showed various degrees of uptake of MIBG.
      Patients operated on at < or =55 days of age showed positive MIBG uptake much
      more frequently than those operated on at later ages. Heart rate and rate
      pressure product at peak exercise on a treadmill exercise test were significantly
      greater in patients with positive uptake than in those with absent uptake of
      MIBG. CONCLUSIONS: Cardiac sympathetic nerves were denervated early after and
      reinnervated late after ASO. Neonatal ASO may be favorable to facilitate
      sympathetic reinnervation, which may affect exercise tolerance late after
      surgery.

PMID- 9641692
TI  - Differential leukotriene constrictor responses in human atherosclerotic coronary
      arteries.
AB  - BACKGROUND: Leukotrienes are a class of biologically active lipids that have
      potent effects on the heart. To assess their role in coronary artery disease, we
      compared the contractile responses of leukotriene C4 (LTC4) and leukotriene D4
      (LTD4) and their binding activity in both atherosclerotic and nonatherosclerotic
      human coronary arteries. We also studied expression of the enzymes that control
      their formation to understand how the 5-lipoxygenase (5-LO) pathway is activated
      in the coronary arteries. METHODS AND RESULTS: The capacity of leukotrienes to
      affect coronary vessel tone and the influence of atherosclerosis was tested in
      organ baths. Leukotriene receptors were examined by autoradiography, and antibody
      binding to the various enzymes responsible for their formation was assessed by
      use of immunocytochemistry. Nonatherosclerotic coronary artery ring segments were
      unresponsive to LTC4 and LTD4. In contrast, LTC4 and LTD4 induced concentration
      dependent contractions in atherosclerotic coronary arteries. Specific [3H]-LTC4
      but not LTD4 binding to atherosclerotic coronary artery was evident, with no
      evidence of specific binding of [3H]-leukotrienes to nonatherosclerotic coronary
      artery. High-resolution autoradiography identified specific [3H]-LTC4 binding
      sites to smooth muscle cell and to regions of intimal proliferation and plaque.
      Cells showing positive antibody binding to 5-LO, FLAP (5-lipoxygenase activating
      protein), and leukotriene A4 hydrolase were also present in the coronary arteries
      and had a similar distribution to macrophages. CONCLUSIONS: Atherosclerosis is
      associated with a specific leukotriene receptor(s) capable of inducing
      hyperreactivity of human epicardial coronary arteries in response to LTC4 and
      LTD4.

PMID- 9641694
TI  - A recessive variant of the Romano-Ward long-QT syndrome?
AB  - BACKGROUND: The congenital long-QT syndrome (LQTS) is a genetically heterogeneous
      disease characterized by prolonged ventricular repolarization and life
      threatening arrhythmias. Mutations of the KVLQT1 gene, a cardiac potassium
      channel, generate two allelic diseases: the Romano-Ward syndrome, inherited as a
      dominant trait, and the Jervell and Lange-Nielsen syndrome, inherited as an
      autosomal recessive trait. METHODS AND RESULTS: A consanguineous family with the
      clinical phenotype of LQTS was screened for mutations in the KVLQT1 gene.
      Complementary RNAs for injection into Xenopus oocytes were prepared, and currents
      were recorded with the double microelectrode technique. A homozygous missense
      mutation, leading to an alanine-to-threonine substitution at the beginning of the
      pore domain of the KVLQT1 channel, was found in the proband, a 9-year-old boy
      with normal hearing, a prolonged QT interval, and syncopal episodes during
      physical exercise. The parents of the proband were heterozygous for the mutation
      and had a normal QT interval. The functional evaluation of the mutant channel
      activity showed reduction in total current, a hyperpolarizing shift in
      activation, and a faster activation rate consistent with a mild mutation likely
      to require homozygosity to manifest the phenotype. CONCLUSIONS: These findings
      provide the first evidence for a recessive form of the Romano-Ward long-QT
      syndrome and indicate that homozygous mutations on KVLQT1 do not invariably
      produce the Jervell and Lange-Nielsen syndrome. The implications of this
      observation prompt a reconsideration of the penetrance of different mutations
      responsible for LQTS and suggest that mild mutations in LQTS genes may be present
      among the general population and may predispose to drug-induced ventricular
      arrhythmias.

PMID- 9641695
TI  - New method for nonfluoroscopic endocardial mapping in humans: accuracy assessment
      and first clinical results.
AB  - BACKGROUND: Accurate mapping of the site of origin and activation sequence of a
      cardiac arrhythmia is essential for a successful catheter ablation procedure. To
      achieve this, precise and reproducible catheter manipulation is mandatory. The
      aim of this study was (1) to assess the accuracy of a new nonfluoroscopic mapping
      system in humans and (2) to report the first result of endocardial activation
      mapping with this system during sinus rhythm and several types of
      supraventricular and ventricular tachycardias. METHODS AND RESULTS: Fifteen
      patients were studied. Accuracy measurements were performed in 5 of them
      (patients 5, 6, 7, 8, and 14). The distances between two subsequent catheter
      positions in the inferior caval vein as determined by the nonfluoroscopic mapping
      system were compared with measurements made with calipers by four independent
      investigators using identification marks on the catheter shaft. The difference
      between these two methods was 0.95+/-0.8 mm. In 15 patients, activation of the
      right atrium and/or the right or left ventricle was recorded during sinus rhythm.
      Three-dimensional activation maps were constructed in patients with atrial and
      ventricular tachycardias and Wolff-Parkinson-White syndrome. CONCLUSIONS: With
      this new nonfluoroscopic mapping technique, accurate positioning of the catheter
      tip is possible. A three-dimensional activation map can be reconstructed during
      sinus rhythm and during supraventricular and ventricular tachycardias of
      different compartments of the heart.

PMID- 9641696
TI  - Lipid lowering by diet reduces matrix metalloproteinase activity and increases
      collagen content of rabbit atheroma: a potential mechanism of lesion
      stabilization.
AB  - BACKGROUND: Proteolytic enzyme activity in lipid-rich atheroma may promote plaque
      rupture and precipitate acute coronary syndromes. This study tested the
      hypothesis that lipid lowering stabilizes plaques by reducing proteolytic
      activity. METHODS AND RESULTS: We produced experimental atheroma in 33 rabbits by
      balloon injury and an atherogenic diet (0.3% cholesterol and 4.7% coconut oil)
      for 4 months. At that time, 15 rabbits were killed (baseline group). The
      remaining animals were divided into two groups: a hyperlipemic group continued to
      consume a cholesterol-enriched diet (0.05% to 0.2%) for 16 more months (n=5) and
      a lipid-lowering group consumed a purified chow diet with no added cholesterol or
      fat for 8 (n=3) or 16 months (n=10). Macrophage accumulation and interstitial
      collagenase (matrix metalloproteinase-1, MMP-1) expression in the lesion were
      measured by quantitative image analysis of standardized sections of immunostained
      aortas. Baseline lesions expressed high levels of MMP-1 and contained many
      macrophages. These features of plaque instability persisted in the hyperlipemic
      group. However, the lipid-lowering group showed progressive reduction in both
      macrophage content and MMP- 1 immunoreactivity with time. Aortic rings of the
      baseline and hyperlipemic groups elaborated gelatinolytic, caseinolytic, and
      elastinolytic activity attributable to MMP-2, MMP-3, or MMP-9, monitored by SDS
      PAGE zymography. Proteolytic activity decreased markedly in the lipid-lowering
      group. Aortic content of interstitial collagen, determined by sirius red
      staining, increased in the lipid-lowering group compared with the baseline or
      continued hyperlipemic groups, indicating that lipid lowering reinforced the
      fibrous skeleton of the atheroma. CONCLUSIONS: These results establish a
      mechanism by which lipid lowering may stabilize vulnerable plaques by reduced
      expression and activity of enzymes that degrade the arterial extracellular matrix
      and render atheroma less susceptible to disruption and thrombosis by favoring
      collagen accumulation in the fibrous cap.

PMID- 9641697
TI  - N-acetyl-cysteine decreases the matrix-degrading capacity of macrophage-derived
      foam cells: new target for antioxidant therapy?
AB  - BACKGROUND: Atherosclerotic plaque destabilization triggers clinical
      cardiovascular disease and thus represents an attractive therapeutic target.
      Weakening of tissue through the action of matrix-degrading enzymes, called matrix
      metalloproteinases (MMPs), released by resident macrophages was previously
      implicated in unstable vascular syndromes. METHODS AND RESULTS: We used a
      hypercholesterolemic rabbit model of atherosclerosis to investigate the
      gelatinolytic activity associated with macrophage-derived foam cells (FCs).
      Gelatinolytic activity and expression of MMP-9 but not of MMP-2 cosegregated with
      macrophage FCs in aortic lesions. Macrophage-derived gelatinases were further
      investigated in vitro. MMP-9 was identified as the main macrophage-derived
      gelatinase in cells isolated from aortic lesions and from granuloma induced in
      the same rabbits to increase cell yield. Importantly, detection of activated MMP
      9 in the FC culture medium supports the notion that these cells can independently
      initiate processing of secreted MMP zymogens to active enzymes. We further
      examined whether FC gelatinolytic activity is dependent on the presence of
      reactive oxygen species (ROS). We found that treatment (1 to 5 days) with 1 to 10
      mmol/L N-acetyl-L-cysteine (NAC), an ROS scavenger, decreased not only
      gelatinolytic activity but also gelatinase expression by FCs. Similarly, NAC
      treatment of explanted lesions abolished in situ gelatinolytic activity and MMP-9
      expression. CONCLUSIONS: Macrophage FCs are an abundant source of gelatinolytic
      activity that can be inhibited in vitro and in situ by NAC. This newly described
      action of antioxidant therapy might prove useful to inhibit matrix degradation
      and to improve vascular stability.

PMID- 9641698
TI  - Profound underestimation of glucose uptake by [18F]2-deoxy-2-fluoroglucose in
      reperfused rat heart muscle.
AB  - BACKGROUND: [18F]2-deoxy-2-fluoroglucose (FDG) is widely used as a tracer for
      glucose uptake in ischemic heart muscle. We tested the effects of low-flow
      ischemia and reperfusion on the ratio of tracer/tracee (lumped constant, LC).
      METHODS AND RESULTS: Isolated working rat hearts were perfused with Krebs
      Henseleit buffer containing only glucose 5 mmol/L (group 1) or glucose 5 mmol/L
      plus oleate 0.4 mmol/L (group 2, fed; group 3, fasted). Dynamic glucose uptake
      was measured simultaneously with [2-3H]glucose and with FDG. After 20 minutes,
      coronary flow was reduced by 75% for 30 minutes before it was returned to control
      conditions for the final 20 minutes. Hexokinase activity in the cytosolic and
      mitochondrial fractions and tissue metabolites were determined. Rates of glucose
      uptake were highest when glucose was the only substrate. Glucose uptake, FDG
      uptake, and the LC increased during ischemia only in group 3. There was no change
      of these parameters during ischemia in groups 1 and 2. FDG uptake decreased
      significantly with reperfusion in groups 2 and 3, and there was a striking fall
      in the LC (from >1.0 to <0.2, P<.001). The fall in the LC was associated with a
      significant increase in intracellular free glucose. Neither ischemia nor
      reperfusion affected the kinetic properties of hexokinase. CONCLUSIONS: FDG
      profoundly underestimates glucose uptake during reperfusion in the presence of
      fatty acids. In the fasted state, however, FDG overestimates glucose uptake
      during ischemia. The results indicate limitations in the use of FDG to quantify
      myocardial glucose uptake in human heart.

PMID- 9641699
TI  - Mitochondrial ATP-dependent potassium channels: novel effectors of
      cardioprotection?
AB  - BACKGROUND: Brief interruptions of coronary blood flow paradoxically protect the
      heart from subsequent prolonged ischemia. The basis of such endogenous
      cardioprotection, known as "ischemic preconditioning," remains uncertain.
      Pharmacological evidence has implicated ATP-dependent potassium (KATP) channels
      in the mechanism of preconditioning; however, the effects of sarcolemmal KATP
      channels on excitability cannot account for the protection. METHODS AND RESULTS:
      We simultaneously measured flavoprotein fluorescence, an index of mitochondrial
      redox state, and sarcolemmal KATP currents in intact rabbit ventricular myocytes.
      Our results show that diazoxide, a KATP channel opener, selectively activates
      mitochondrial KATP channels. Diazoxide induced reversible oxidation of
      flavoproteins with an EC50 of 27 micromol/L but did not activate sarcolemmal KATP
      channels. The subcellular site of diazoxide action is further localized to
      mitochondria by confocal imaging of fluorescence arising from flavoproteins and
      tetramethylrhodamine ethyl ester. In a cellular model of simulated ischemia,
      inclusion of diazoxide decreased the rate of cell death to about half of that in
      controls. Both the redox changes and protection are inhibited by the KATP channel
      blocker 5-hydroxydecanoic acid. CONCLUSIONS: Our results demonstrate that
      diazoxide targets mitochondrial but not sarcolemmal KATP channels and imply that
      mitochondrial KATP channels may mediate the protection from KATP channel openers.

PMID- 9641700
TI  - Images in cardiovascular medicine. Intramyocardial dissecting hematoma.

PMID- 9641701
TI  - Images in cardiovascular medicine. Infected dual-chamber pacemaker leads.

PMID- 9641702
TI  - The American Heart Association Stroke Outcome Classification: executive summary.

PMID- 9641703
TI  - Youth violence: If we are not active in prevention efforts, who will be?

PMID- 9641704
TI  - Violence exposure and emotional trauma as contributors to adolescents' violent
      behaviors.
AB  - OBJECTIVE: To investigate the degree to which violence exposure and symptoms of
      psychological trauma are related to adolescents' own violent behaviors. DESIGN
      AND SETTING: Anonymous self-report questionnaire administered to students in 6
      public high schools (grades 9-12). PARTICIPANTS: Sixty-eight percent of the
      students attending the participating schools during the survey participated in
      the study (N=3735). Ages ranged from 14 to 19 years; 52% were female; and 35%
      were African American, 33% white, and 23% Hispanic. RESULTS: Multiple regression
      analysis determined that violence exposure and symptoms of psychological trauma
      together explained more than 50% of the variance in both male and female self
      reported violent behavior. The independent effects of exposure to violence
      explained about one quarter of the variance in both male and female adolescents'
      violent behaviors. Anger was found to be the leading trauma symptom. CONCLUSION:
      Our findings suggest that health clinicians and other professionals who encounter
      adolescents should routinely screen them for both exposure to violence and
      symptoms of anger.

PMID- 9641705
TI  - Do children with primary nocturnal enuresis have clinically significant behavior
      problems?
AB  - OBJECTIVE: To determine if primary nocturnal enuresis (PNE) is accompanied by
      significant behavioral comorbidity. DESIGN: A survey design using a standardized
      behavioral rating scale. SETTING: Behavioral pediatric clinics in the Midwest.
      PARTICIPANTS: Subjects with PNE (n=92) were selected from 122 consecutive
      referrals for enuresis. Criteria included age 5 years or older, PNE status, and
      wetting frequency of at least once per week. The clinical sample without PNE
      (n=92) was randomly selected from 429 consecutive referrals to the same pediatric
      clinics, stratified for age and sex. The nonclinical sample (n=92) was randomly
      selected by strata from the standardization sample (N=614) of the behavioral
      checklist used in the study. MAIN OUTCOME MEASURE: The Eyberg Child Behavior
      Inventory (ECBI), a standardized parent report scale, was used to measure the
      degree of behavioral comorbidity. The ECBI yields 2 scores, Problem Intensity and
      Problem Number. RESULTS: Results from 2 separate 3 (group) x 2 (sex) analyses of
      variance indicated a significant main effect for group on Problem Intensity and
      Problem Number (P<.001). For Problem Intensity, post hoc comparisons indicated
      the mean of the PNE sample was significantly higher than the mean of the
      nonclinical sample (P<.05), but the mean scores of the clinical sample were
      significantly higher than those of both the PNE and nonclinical samples (P<.05).
      For Problem Number, post hoc comparisons revealed the means of the PNE and
      nonclinical samples did not differ from each other (P>.05) but were lower than
      the mean of the clinical sample (P<.05). CONCLUSION: Primary nocturnal enuresis
      does not present with significant behavioral comorbidity in most cases. The
      results suggest that, with the exception of an extraordinary clinical
      presentation, pediatricians should treat PNE as a common biobehavioral problem
      without a psychiatric component.

PMID- 9641706
TI  - Sudden infant death with external airways covered: case-comparison study of 206
      deaths in the United States.
AB  - OBJECTIVE: To study factors associated with sudden infant deaths occurring with
      the external airways (ie, nose and mouth) covered by bedding. DESIGN: Case
      comparison study of infants dying with vs those dying without the external
      airways covered. SETTING: Death-scene investigation and reconstruction at the
      site of death using an infant mannequin; 18 metropolitan areas. PARTICIPANTS:
      Caregivers for a consecutive sample of infants who died of sudden infant death
      syndrome (SIDS). Complete data from 206 of 382 eligible cases. MAIN OUTCOME
      MEASURES: Among infants dying suddenly and unexpectedly, an analysis of whether
      sociodemographic risk factors for SIDS, sleep practices, or bedding increased the
      risk of dying with the external airways covered. RESULTS: Data were analyzed by
      using univariate and 2 types of multivariate risk analysis, logistic regression
      and latent class. Of the victims, 59 (29%) were found with the external airways
      covered. Conventional risk factors for SIDS did not affect the risk of death with
      the external airways covered. Factors increasing the risk of death with the
      external airways covered included prone sleep position (odds ratio [OR], 2.86)
      and using soft bedding (OR, 5.28), such as comforters (OR, 2.46) and pillows (OR,
      3.31). Infants at low risk for death with the external airways covered slept in
      the prone position, but rarely on a pillow, comforter, or other bedding that
      allowed a pocket to form beneath the face. All 9 infants who were positioned
      supine or on one side for sleep and found with the external airways covered had
      turned and were found dead in the prone position. CONCLUSIONS: Sudden infant
      deaths with the external airways covered were common in the United States when
      most infants slept prone. Soft bedding, including pillows and comforters,
      increased the risk that an infant who died would be found with the external
      airways covered. Therefore, these items should not be placed near infants,
      regardless of the sleep position.

PMID- 9641707
TI  - Accuracy and reproducibility of blood lead testing in commercial laboratories.
AB  - OBJECTIVE: To assess the proficiency of commercial laboratories in analyzing lead
      in clinical blood samples from subjects without overt lead exposure. DESIGN: We
      submitted masked duplicate blood lead specimens to 8 masked laboratories. Each
      laboratory received blood aliquots immediately following drawing (time 1) and 2
      weeks later (time 2) from 7 human subjects and 3 bovine blood samples with known
      lead levels of 0.26, 0.57, and 0.79 micromol/L (5.4, 11.8, and 16.4 microg/dL).
      Of the 8 laboratories, 5 were commercial laboratories, 1 was a state laboratory,
      1 was a research laboratory, and 1 was the Centers for Disease Control and
      Prevention reference laboratory. OUTCOME MEASURES: Correlation coefficients were
      calculated, and differences within and between laboratories were assessed by
      analysis of variance. RESULTS: Results were obtained for all specimens, with all
      the human subjects' overall mean lead levels being less than 0.48 micromol/L (<10
      microg/dL). Each laboratory reported all human blood specimens appropriately, as
      having lead levels less than 0.48 micromol/L (<10 microg/dL) and within 0.14
      micromol/L (3 microg/dL) of the overall mean for that subject. All internal
      reproducibilities were very high (range, 0.92-1.00) except for one (0.60),
      possibly lower because of 1 pair of specimens. Mean differences between blood
      samples analyzed at time 1 and time 2 ranged from -1.4 to 1.2, with only 2
      laboratories having significant differences (P<.01). CONCLUSIONS: Overall, there
      was strong reproducibility within and among laboratories, with no overall time
      trend or interlaboratory or intralaboratory variance. The storage conditions did
      not seem to affect the aggregate results. The data suggest that through
      implementation of the Centers for Disease Control and Prevention/Wisconsin Blood
      Lead Proficiency Testing Program, the Centers for Disease Control and
      Prevention's Blood Lead Laboratory Reference System, and mandated federal and
      state proficiency programs, laboratories in this geographic region have improved
      their performance as compared with previous published studies and an unpublished
      study.

PMID- 9641708
TI  - Compliance with universal precautions among pediatric residents.
AB  - BACKGROUND: There are few data on the rate of compliance with universal
      precautions among pediatricians. We hypothesized that compliance in pediatrics
      would be poor because of the intrinsic difficulties in performing invasive
      procedures in small subjects. DESIGN: Prospective, observational study. SETTING:
      Tertiary care children's hospital. STUDY PARTICIPANTS: A convenience sample of
      pediatric house staff. MAIN OUTCOME MEASURES: Pediatric house staff members were
      observed while performing invasive procedures. Procedure type, number of attempts
      required, and patient's age and diagnosis were recorded. Degree of compliance
      with universal precautions was judged by means of Centers for Disease Control and
      Prevention guidelines. Comparisons between the compliant and noncompliant groups
      were analyzed by chi2 and 2-tailed t test. RESULTS: A total of 128 procedures
      performed by 43 house officers, 4 advanced medical students, and 3 chief
      residents or fellows were observed. Sixty-nine (53.9%) of the 128 procedures were
      performed correctly according to universal precaution guidelines. Rate of
      compliance did not appear to be influenced by small patient size, as judged by
      the lack of association with the age of the patient (mean+/-SD, 4.8+/-5.7 years
      among those in whom universal precautions were properly used vs 4.9+/-5.4 years
      among patients in whom precaution guidelines were breached; P=.96). Moreover, the
      number of attempts required in compliant procedures (1.31+/-0.53) was almost
      identical to that in noncompliant procedures (1.28+/-0.49; P=.73). Additionally,
      compliance did not improve with advanced level of training. CONCLUSIONS: Failure
      of compliance among pediatricians has no apparent association with procedure
      difficulty, and compliance rates continue to be poor through the course of
      pediatric training. These findings underline the need for effective education
      concerning universal precautions throughout pediatric residency, and they suggest
      that such efforts will not be precluded by obstacles intrinsic to performing
      invasive procedures on young subjects.

PMID- 9641709
TI  - Autopsies in children: are they still useful?
AB  - BACKGROUND: Autopsy has traditionally been the criterion for determining cause of
      death and has played a major role in medical education and quality control. With
      increasing use of bedside technology, however, autopsy rates have steadily
      declined. OBJECTIVE: To identify (1) trends in pediatric autopsy rates during the
      past decade, (2) concordance between antemortem and postmortem diagnoses, and (3)
      patient characteristics influencing autopsy rates or diagnostic yield. METHODS:
      All pediatric deaths between January 1, 1984, and December 31, 1993, were
      retrospectively reviewed. Data collection included demographics for all patients,
      and length of stay, diagnostic imaging studies, antemortem diagnoses, and autopsy
      findings for patients with autopsies. Autopsy diagnoses were compared with
      antemortem findings and classified according to their concordance. RESULTS: Of
      297 pediatric deaths, autopsies were performed on 107 patients (36%). Autopsy
      rates did not change significantly during the study period. Autopsies were not
      associated with patient gender, race, or insurance status, but increased
      significantly with age. Autopsies were performed in 26% of infants 12 months or
      younger, 60% of children between 13 to 60 months of age, and 100% of children 61
      months or older (chi2; P <.001). In 34% of cases, new diagnoses were made at
      autopsy, including 7 cases where new findings, if known before death, would
      likely have resulted in a change in treatment or improved survival. There was no
      relationship between new findings at autopsy and age, length of hospital stay, or
      antemortem imaging studies. CONCLUSIONS: Autopsy can provide additional
      information in more than one third of pediatric deaths. Pediatric autopsy
      continues to provide clinically significant data and remains a valuable tool in
      modern pediatric practice.

PMID- 9641710
TI  - Health status of pediatric refugees in Portland, ME.
AB  - BACKGROUND: An understanding of the health conditions affecting pediatric
      refugees is essential to providing responsible health care for them when they
      arrive in the United States. OBJECTIVE: To assess the health status of pediatric
      refugees in an area of increased refugee resettlement. DESIGN: Retrospective
      medical records review. SETTING: Ambulatory clinic at Maine Medical Center in
      Portland, a community and referral hospital. PATIENTS: One hundred thirty-two
      refugees and immigrants aged 2 months through 18 years who had initial health
      care evaluations during 1994 and 1995. RESULTS: Sixty-six patients arrived from
      Africa, 22 from the former Yugoslavia, and the remainder from the former Soviet
      Union, Middle Asia, Southeast Asia, and Latin America. The mean age of the
      patients was 10 years; 56 (42.4%) were female. The overall health status of most
      of the children was good, with most having appropriate weight and height for age.
      Dental caries and dermatologic conditions were the most prevalent findings on
      physical examination. Two patients had evidence of traumatic injuries. The
      results of tuberculin (Mantoux) tests were positive (> or =10 mm) in 45 (35.2%)
      of 128 children for whom results were noted, hepatitis B surface antigen was
      detected in 5 (4.0%) of 124 children, and hepatitis B surface antibody was
      detected in 26 (21.1%) of 123 children. Five (16.7%) of 30 children younger than
      6 years had elevated blood lead levels; anemia was detected in 25 (19.7%) of 127
      children with hematocrit results available. Stool specimens were obtained from 87
      patients, of whom 38 (43.7%) had pathogenic parasites in at least 1 specimen.
      CONCLUSIONS: Pediatric refugees arrive in the United States with a variety of
      conditions that may be unfamiliar to practitioners trained in this country. The
      results of this study support the screening of refugees from Africa and other
      regions for tuberculosis, stool parasites, and hepatitis B.

PMID- 9641711
TI  - Distress symptoms among urban African American children and adolescents: a
      psychometric evaluation of the Checklist of Children's Distress Symptoms.
AB  - OBJECTIVES: To explore the factor structure of the Checklist of Children's
      Distress Symptoms (CCDS); to examine whether there is a higher-order single
      construct underlying the CCDS measure; and, to assess the association between
      children's distress symptoms, as reflected by the CCDS factors, and children's
      self-reported exposure to community violence (both victimization and witness
      events). DESIGNS: Community-based cross-sectional survey. SETTINGS: Ten public
      housing developments in an eastern metropolis. PARTICIPANTS: A total of 349 low
      income urban African American children and adolescents (198 males; 151 females),
      9 through 15 years of age. MEASURES: Children's distress symptoms, exposure to
      community violence, and selected demographic information including parental
      education, parental employment status, perceived health status, and school
      performance. ANALYSIS: Exploratory factor analysis was performed to determine the
      factorial structure of the CCDS measure. Second-order confirmatory factor
      analysis was performed to determine if there is a higher-order single underlying
      construct among CCDS factors. Pearson correlation coefficients were computed to
      assess the relationship between exposure to violence and CCDS factors. MAJOR
      FINDINGS: The exploratory factor analysis yielded a 6-factor solution for the
      CCDS measure with satisfactory internal consistency. The confirmatory factor
      model with a single second-order construct yielded a good fit to the data. In
      general, youth who experienced violent victimization or witnessed violent events
      reported higher levels of distress symptoms than those who did not. Distress
      symptoms labeled as "intrusive thoughts," "distraction," and "lack of
      belongingness" were most frequently associated with exposure to violence.
      Distress symptoms did not differ on the basis of sex or age. CONCLUSIONS: The
      CCDS has utility as a measure of distress symptoms among urban African American
      children and adolescents. Whereas analysis provided support for a single higher
      order construct, using the proposed 6-factor structure should enhance our
      understanding of the psychological impact of exposure to violence on youth and
      contribute to more effective intervention efforts.

PMID- 9641712
TI  - Group well-child care for high-risk families: maternal outcomes.
AB  - OBJECTIVE: To determine if participation in group sessions as part of health
      supervision visits for infants improves outcomes compared with individual visits
      in high-risk mothers. STUDY DESIGN: Randomized controlled clinical trial.
      PARTICIPANTS: Mothers of young infants who had at least 1 of the following risk
      factors: aged younger than 20 years at delivery, participation in Medicaid, less
      than a high school education, previous or ongoing substance abuse, or history of
      abuse as a child. SETTING: Two urban university pediatric clinics in Seattle,
      Wash. INTERVENTIONS: Mother-infant dyads were randomized to receive group well
      child care (GWCC) or individual well-child care (IWCC) before the infant was 4
      months old; the intervention continued until the child was 15 months old. Mothers
      completed the Sense of Competence and Social Isolation subscales from the
      Parenting Stress Index and Sarason's Social Support Questionnaire at enrollment
      and again on completion of the study. During the 11-month study period, 7 health
      supervision visits were scheduled for each mother-infant dyad. Social workers met
      periodically with mothers during the study and assessed the following functional
      outcomes: return to school, return to work, enrollment in a substance abuse
      treatment program, and becoming pregnant. In addition, data on study children
      were collected from Child Protective Services to assess referrals because of
      suspected abuse and/or neglect. RESULTS: Data were collected on 213 mother-infant
      dyads, including 108 who received GWCC and 105 who received IWCC. At the
      conclusion of the study period, similar proportions of GWCC and IWCC mothers
      scored in the high-risk range on the Sense of Competence subscale, Social
      Isolation subscale, and the Social Support Questionnaire (P=.57, .32, and .59,
      respectively). For more than 50% of the mothers, scores on the Sense of
      Competence and Social Isolation subscales deteriorated during the study period
      from the not-high-risk range to the high-risk range, regardless of assignment to
      GWCC or IWCC. No differences were noted between GWCC and IWCC mothers for any
      functional outcome. During the study period, 8.8% of children receiving GWCC were
      referred to Child Protective Services vs 8.3% of those receiving IWCC (P=.85).
      CONCLUSION: The format of well-child care may not be an important determinant of
      outcomes among high-risk mothers.

PMID- 9641713
TI  - The physicians' office laboratory: 1988 and 1996 survey of Illinois
      pediatricians. Pediatric Practice Research Group.
AB  - OBJECTIVES: To contrast practices of physicians' office laboratories in the years
      1988 and 1996 and ascertain physicians' perception of the effect of the Clinical
      Laboratory Improvement Amendments of 1988 (CLIA). DESIGN: Mailed surveys to
      members of the Illinois chapter of the American Academy of Pediatrics in 1988 and
      1996. SUBJECTS: There were 525 and 980 respondents in 1988 and 1996,
      respectively; analyses included 282 and 374 surveys representing offices where
      direct patient care was provided in a nonhospital setting. A paired analysis was
      also conducted on 101 offices that responded to both surveys. RESULTS: There was
      a decline from 1988 to 1996 in the percentage of offices doing in-office
      laboratory testing (93% to 84%, respectively; chi2 test; P<.01) and median number
      of types of tests (6 tests vs 4 tests; Mann-Whitney U test; P<.001). Decreases
      (chi2 test; P<.01) were seen in the proportion of offices offering throat culture
      for group A streptococci (63% to 33%), urinalysis (54% to 33%), urine culture
      (53% to 22%), rapid hemagglutination slide test for mononucleosis (42% to 17%),
      theophylline level (27% to 4%), and total cholesterol (22% to 13%). The
      proportion of offices offering urine dipstick, hematocrit or hemoglobin, complete
      blood cell count, and stool occult blood tests remained stable. For solo
      practitioner offices only, streptococcal antigen detection testing decreased (66%
      to 39%; chi2 test; P<.001). Findings in the paired analyses were similar. In
      1996, more offices participated in a formal proficiency testing program (60% vs
      11%; chi2 test; P<.001). The CLIA guidelines were deemed responsible for
      increased documentation (58%), discontinuing 1 or more tests (56%), increased
      frequency of quality control (50%), joining a proficiency program (40%), and
      increased cost to patients (32%). CONCLUSIONS: These surveys provide large-scale
      data concerning change in office-based laboratories of physicians serving
      children during an 8-year period. Office laboratories reduced their menu of tests
      and enhanced documentation and quality control for the tests that were done. Data
      like these in multiple specialties over time contribute to a comprehensive
      picture of the effects of CLIA on office laboratory practices.

PMID- 9641714
TI  - Treatment of the acute crisis in maple syrup urine disease.
AB  - BACKGROUND: The acute crisis of metabolic decompensation in maple syrup urine
      disease is a potentially lethal medical emergency that requires reduction in
      concentrations of leucine and other branched-chain amino acids in plasma.
      Experience with intravenous mixtures of amino acids indicates that this can be
      accomplished by the synthetic forces of protein synthesis. However, these
      intravenous mixtures are not generally available. OBJECTIVE: To develop enteral
      mixtures suitable for administration by nasogastric drip in minimal volume.
      DESIGN: Mixtures of amino acids were designed containing no leucine, isoleucine,
      or valine for administration by nasogastric drip. Needs for water and calories
      were to be met intravenously. They were designed to be used in the management of
      the acute crisis. SETTING: Inpatient pediatric service. PATIENTS: Two patients
      with maple syrup urine disease. Data were collected during the management of 3
      episodes of metabolic imbalance. INTERVENTION: Studies were carried out for 4 to
      11 days, during which there was no intake of leucine. Four different mixtures
      were used and a fifth was designed on the basis of this experience. MAIN OUTCOME
      MEASURES: Effects on the concentrations of leucine and the other branched-chain
      amino acids. Clinical status closely mirrored the concentration of leucine.
      RESULTS: In each instance, a progressive fall in leucine concentration was
      obtained. Rates of fall were comparable to those obtained with intravenous
      therapy. Concentrations of isoleucine fell to levels that made this amino acid
      limiting for protein synthesis and hence therapeutic effect. This led to greater
      and earlier supplementation with isoleucine. Valine supplementation was also
      useful. CONCLUSIONS: The acute crisis of metabolic imbalance in maple syrup urine
      disease may be effectively treated by the continuous intragastric drip of
      solutions of amino acids devoid of leucine along with provision of water and
      calories intravenously.

PMID- 9641715
TI  - Radiological case of the month. Neonatal gastric perforation.

PMID- 9641716
TI  - Picture of the month. Bilateral nasal septal hematomas.

PMID- 9641717
TI  - Pathological case of the month. Erythropoietic protoporphyria.

PMID- 9641718
TI  - Professional identity and its responsibilities.

PMID- 9641719
TI  - Hegel, the Nazis, and child euthanasia.

PMID- 9641720
TI  - Sitting at the top of the slope.

PMID- 9641721
TI  - Bulging anterior fontanel.

PMID- 9641722
TI  - Varicella vaccination in a primary care pediatric practice.

PMID- 9641723
TI  - The Physicians' Desk Reference should not be held as a legal standard of medical
      care.

PMID- 9641724
TI  - Views on growth hormone treatment in idiopathic shortness of stature.

PMID- 9641725
TI  - The genetics of nocturnal enuresis: a simple question of complexity.

PMID- 9641726
TI  - Drug prescribing for children in general practice.

PMID- 9641727
TI  - Adhesion inhibitory activity of beta-lactoglobulin isolated from infant formulae.
AB  - Beta-lactoglobulin was isolated from infant formulae that were ultra high
      temperature (UHT) -treated, sterilized or spray-dried. The effect of the isolated
      beta-lactoglobulin on SfaII-fimbriae-mediated adhesion of Escherichia coli to
      human ileostomy glycoproteins was studied in vitro. Beta-lactoglobulin isolated
      from sterilized formulae was found to perform significantly less well than
      preparations from spray-dried formulae (p = 0.05). Great heterogeneity was
      observed in the adhesion inhibitory capacity of beta-lactoglobulin isolated from
      UHT-treated formulae. Therefore, no significant difference was observed between
      UHT-treated and sterilized formulae or spray-dried formulae (p > 0.10). It can be
      hypothesized that beta-lactoglobulin from spray-dried and some UHT-treated infant
      formulae may affect the colonization of mucous membranes by E. coli strains
      causing neonatal septicaemia and meningitis.

PMID- 9641728
TI  - Influence of weight, age and puberty on bone size and bone mineral content in
      healthy children and adolescents.
AB  - The biology of bone mineralization during growth is important for peak bone mass.
      The aim of the study was to examine how body size, age and puberty influence bone
      size and bone mineral density. Whole body bone area (BA) and bone mineral content
      (BMC) were examined by dual-energy X-ray absorptiometry (Hologic 1000/W) in
      healthy girls (n = 201) and boys (n = 142) aged 5-19 y. The influence of height,
      weight, age and puberty on bone mineralization was examined by multiple
      regression. Main determinants of BA were height and weight. Bone width,
      approximated by BA corrected for height, increased highly significantly with
      weight and depended weakly significantly on pubertal stage. Main determinants of
      BMC were BA, height, age and pubertal stages. Bone mineral density, approximated
      by BMC corrected for BA and height, depended on age and pubertal stage, but not
      on weight. Thus skeletal size is mainly determined by body size, while bone
      density is determined by age and pubertal stage.

PMID- 9641729
TI  - Serum digoxin-like immunoreactive factor in children and its relation to sodium
      metabolism.
AB  - Serum digoxin-like immunoreactive factor (DLIF), an endogenous substance that
      cross-reacts with antidigoxin antibodies, was assessed (fluorescence polarization
      immunoassay) in children (n = 134) aged 5-16 y, who had never been treated with
      cardiac glycosides. DLIF was found in 50% of serum samples at a mean
      concentration of 0.16 +/- 0.06 ng/ml (range 0.03-0.35 ng/ml). Although the study
      population as a whole was apparently homogeneous with regard to serum sodium
      content, and none had clinical signs of sodium imbalance, children with DLIF
      showed significantly lower natraemia (p = 0.0002), higher urinary concentration
      (p = 0.001) and fractional excretion (p = 0.001) of sodium, and increased
      systolic blood pressure (p = 0.009) compared with children without DLIF. Inverse
      correlations were found between DLIF concentration and serum sodium (p < 0.01),
      urine sodium content (p < 0.001), 24-h sodium excretion (p < 0.001), systolic (p
      < 0.001) and diastolic (p < 0.01) blood pressure. These findings suggest that
      sodium handling is different in children with and without DLIF, since this
      material seems to be released preferably in subjects who show a trend towards
      negative sodium balance. Such an association suggests that DLIF may be a
      physiologically relevant material involved in sodium homeostasis.

PMID- 9641730
TI  - Exploration of glucose homeostasis during fasting in growth hormone-deficient
      children.
AB  - In order to define more precisely the risk of hypoglycaemia in GH-deficient
      children and to clarify the role of growth hormone (GH) in glucose homeostasis, a
      24-h fast was monitored in 10 GH-deficient children aged 1.1-6.5 y. Asymptomatic
      hypoglycaemia (blood glucose < or = 2.6 mmol/l) occurred in 9/10 children, 2 of
      whom prematurely interrupted the test. Blood glucose profile was not reproducible
      between children and had no correlation with age (p = 0.48). Gluconeogenesis was
      considered as non-altered as read from the normal plasma lactate and pyruvate
      concentrations throughout the test. Plasma ketone body concentrations increased
      during the test, but were lower than expected with respect to the decrease of
      blood glucose. This suggests insufficient ketogenesis which could exacerbate
      hypoglycaemia in GH-deficient children if brain glucose utilization were not
      alleviated by ketone body oxidization, as is normally the case. The positive
      glucose response after glucagon stimulation in 6/10 patients indicated normal
      hepatic glycogen content. However, these responses were unexpected following the
      prolonged fast and its concomitant hypoglycaemia, and would therefore tend to
      suggest a defect in glycogenolysis. These results confirm the tendency to
      hypoglycaemia, even after infancy, in GH-deficient children. These hypoglycaemias
      may occur by different types of malfunctioning, such as insufficient ketogenesis
      or a defect in glycogenolysis. These hypotheses require confirmation by a more
      systematic study of the metabolic and hormonal changes that occur during fasting
      in both GH-deficient and normal children.

PMID- 9641731
TI  - Three-year data from a comparative study with recombinant human growth hormone in
      the treatment of short stature in young children with intrauterine growth
      retardation.
AB  - Growth acceleration and bone maturation were studied for 3 y in 69 children with
      severe short stature and a history of intrauterine growth retardation (IUGR), to
      determine the effect of treatment with recombinant human growth hormone (r-hGH).
      The patients were enrolled in an open, multicentre trial and were randomly
      allocated to either the treated group (Group 1) or the control group (Group 2).
      The children in Group 1 were treated daily with 0.2 IU/kg/body weight (0.067
      mg/kg) s.c., during 3 y and the children in Group 2 started the study with a 1-y
      observation period followed by a 3-y treatment period. At birth, their mean
      weight standard deviation score (SDS) was -2.5 and their mean length SDS -3.5. At
      baseline, the patients were prepubertal, non-GH deficient, with no known
      dysmorphic features. Mean age was 4.5 y, bone age was 3.3 y, height SDS was -3.4,
      height velocity (HV) SDS was -1.6, and body mass index SDS was -1.4. After 1 y of
      treatment, linear HV in Group 1 increased in comparison with the pre-treatment
      period (from 5.7 +/- 2.0 to 10.1 +/- 1.7 cm/y; p < 0.001) and with the first year
      of observation in Group 2 (p < 0.001). Increased HV was sustained during the
      second and third year of treatment and was significantly higher than at baseline.
      A similar growth pattern was seen during the 3 y of GH treatment in Group 2. Mean
      height SDS for chronological age increased by 2.0 +/- 0.7 in the two groups after
      3 y of treatment. HV after 1 y of treatment was negatively correlated with growth
      velocity at baseline. Bone age remained retarded but increased with a mean of
      almost 4 y after 3 y of treatment in both groups. Even at a dose that is three
      times the replacement dose treatment with r-hGH was well tolerated. From these
      results, we conclude that r-hGH treatment over 3 y can induce sustained catch-up
      growth in young children with severe short stature and a history of IUGR. Long
      term studies are needed to assess ultimate effects on final height.

PMID- 9641732
TI  - Once versus twice daily injections of growth hormone in children with idiopathic
      short stature.
AB  - The aim of this study was to compare the growth response of 22 short pre-pubertal
      children without growth hormone deficiency, treated with a single daily growth
      hormone injection (group A), to the growth response of 27 similar children,
      treated with the same daily dose divided into 2 subcutaneous injections per day
      (group B), for 1 y, in a randomized study. GH treatment significantly promoted
      growth parameters, height standard deviation score and height velocity standard
      deviation score in both groups. Serum insulin-like growth factor I was also
      increased. There were no significant differences in growth response, serum IGF-I
      levels, or the advance in bone age between the two study groups after 1 y of GH
      therapy. We conclude that twice daily s.c. growth hormone injections provide no
      advantages over once daily injection of the same dose in promoting the linear
      growth of short children without growth hormone deficiency.

PMID- 9641733
TI  - Adult height comparison between boys and girls with precocious puberty after long
      term gonadotrophin-releasing hormone analogue therapy.
AB  - We examined 22 girls and 11 boys with idiopathic precocious puberty (IPP) treated
      with a GnRH analogue for a period of about 4 y. The purpose of our study was to
      evaluate possible differences between the two sexes in bone growth and skeletal
      maturation during treatment and in the achievement of final height, and also to
      study the relative contribution of particular hormones--sex steroids, DHEAS, GH
      and IGF-I--during the pubertal growth spurt. At the beginning of therapy mean
      chronological age (CA) was 7.61 +/- 0.84 y in boys and 7.32 +/- 1.06 y in girls.
      After the first year of treatment, growth velocity and delta bone age/delta
      chronological age (deltaBA/deltaCA) ratio had declined significantly in both
      groups. At the end of therapy we observed a statistically relevant increase in
      predicted adult height in both sexes, with a more appreciable mean gain
      (expressed as SDS) being achieved by male patients. During the first year
      following discontinuation of treatment, a significant increase in the
      deltaBA/deltaCA ratio was observed in both males and females; by contrast, growth
      velocity increased only in male patients. Adult height SDS was thus greater in
      boys (0.13 +/- 0.91) than in girls (-0.62 +/- 0.88, p < 0.05). With regard to
      endocrinological data, oestradiol and testosterone were significantly reduced
      during the first year of therapy, while DHEAS levels increased slightly in both
      sexes throughout the course of treatment. GH peak after clonidine and IGF-I
      concentrations remained unchanged in both groups. Also, a study of nocturnal GH
      secretion (10 subjects) showed no noteworthy decrease in any of the patients,
      whether in terms of mean GH, of the sum of pulse amplitudes, or of pulse
      frequency. In conclusion, our data indicate that boys achieve more significant
      results in terms of adult height than girls. With reference to endocrinological
      data, the effect of sex steroids on bone maturation seems to be more significant
      than previously thought, and we hypothesize a different role for androgens and
      oestrogens in regulating height velocity and bone maturation in both male and
      female subjects during pubertal growth spurt.

PMID- 9641735
TI  - Ketoacidosis occurring in newly diagnosed and established diabetic children.
AB  - A 6-y retrospective case note review was performed to determine the causes of
      ketoacidosis. 135 patients and 463 diabetic years were involved. Fifty-two
      ketoacidosis episodes occurred: 19 episodes in new patients and 33 episodes in 19
      patients with established diabetes. 27% of newly diagnosed patients presented in
      ketoacidosis. They were similar in terms of age, sex and proportion living in
      single parent families to those presenting without ketoacidosis. The 33
      ketoacidosis episodes occurring in established patients included 12 episodes in 3
      children who were transferred to our care because of uncontrolled diabetes.
      Insulin omission was the cause of ketoacidosis in 9/19 (47%) patients, and was
      suspected in a further 5/19 (26%). Family and school problems were common and
      14/19 patients came from single parent families. Established patients aged > or =
      11 y were predominantly female (10F, 2M), whereas patients aged < or = 10 y were
      predominantly male (6M, 1F). 7 patients with multiple ketoacidosis episodes were
      all > or = 11 y and 6 were female. Families with > or = 2 diabetic children
      appeared vulnerable, 4 cases coming from 3/7 such families.

PMID- 9641734
TI  - Midline brain lesions in children with hormone insufficiency indicate early
      prenatal damage.
AB  - The relationships between midline brain morphology, anterior visual pathway
      morphology and hormonal status in children with impaired growth were studied.
      Intracranial morphology was studied by magnetic resonance imaging in 47 children
      (14F, 33M), median age 9.7y (range 2.6-18.7y) undergoing growth hormone treatment
      (GH; 0.1 U/kg/d). They were chosen to represent various birth sizes and a
      spectrum of hormone insufficiencies. There was a relationship between GH
      secretion and the morphology of the neurohypophysis, the pituitary stalk and the
      anterior visual pathways, i.e. the greater the GH insufficiency, the more
      abnormal were these structures. The children with anterior visual pathway
      abnormalities had the lowest GH levels and the smallest adenohypophysis. The
      association between abnormalities of the anterior visual pathways and the
      hypothalamo-pituitary structures may reflect a common prenatal neural damage in
      embryologically and anatomically closely related structures.

PMID- 9641736
TI  - Transient focal neurologic deficits associated with hypoglycaemia in children
      with insulin-dependent diabetes mellitus. Italian Collaborative Paediatric
      Diabetologic Group.
AB  - We describe 54 transient focal neurologic deficits (TFND) episodes in 44 children
      under 18 y observed retrospectively during a 5-y period (1991-96). Mean age and
      duration of insulin-dependent diabetes mellitus (IDDM) were 8.4 and 3.4 y,
      respectively. None of the children had a history of seizure disorder and only one
      had a personal history of migraine. Twenty-nine episodes were characterized by
      right- and 25 by left-sided hemiparesis. Three of six patients who presented more
      than one event had alternate episodes of right- and left-sided hemiparesis. On 8
      occasions the episode was preceded by a brief convulsion, in 39 it was not
      witnessed, and in 7 it was certainly absent. Hypoglycaemia (< or = 2.77 mmol/l)
      was documented on 26 occasions. On 18 of these 26 occasions, the episodes did not
      resolve promptly after sugar administration. The clinical course was benign, all
      patients remained neurologically normal and none developed migraine at follow up.
      Episodes of TFND were associated with hypoglycaemia in the majority of our cases
      and we do not consider invasive investigations to be mandatory, since the long
      term prognosis was invariably good.

PMID- 9641737
TI  - Normal growth of prepubertal nephrotic children during long-term treatment with
      repeated courses of prednisone.
AB  - The growth of 21 prepubertal children with steroid-dependent frequently relapsing
      nephrotic syndrome was studied before and during treatment with repeated courses
      of oral prednisone for 4 y. The height and height velocity standard deviation
      scores (HSDS and HVSDS) of the nephrotic children were -0.11 and -0.06,
      respectively, at the onset of the disease and -0.12 and +0.05, +0.14 and +1.02,
      +0.21 and +0.78 and +0.17 and +0.66, respectively, thereafter yearly during the
      treatment. The mean yearly cumulative dose of prednisone was 6300, 3459, 2677 and
      2081 mg/body area (m2) at the first, second, third and fourth year, respectively.
      The nephrotic children grew normally for their age before onset of the disease
      and growth remained normal despite prednisone treatment.

PMID- 9641738
TI  - Incidence rate of first-time symptomatic urinary tract infection in children
      under 6 years of age.
AB  - A retrospective population-based study was performed to describe the incidence
      rate of first time symptomatic urinary tract infection in children under 6 y of
      age. A total number of 299 children was identified during the 20-month study
      period in a population of 20,000 girls and 21,000 boys. The cumulative incidence
      rate during the first 6 y of life was 6.6% for girls and 1.8% for boys. The
      annual incidence rate in girls of urinary tract infection/1000 at risk was
      between 9 and 14 for each of the six 1-y age intervals. In girls, the proportion
      of febrile urinary tract infection was high during the infant year, while girls
      older than 2 y most often had non-febrile infection. For infant boys, the
      incidence rate and the proportion of febrile urinary tract infection were
      comparable to that of girls, while after the first year of life urinary infection
      of any kind was rare, with an incidence rate of 1-2/1000 at risk.

PMID- 9641739
TI  - Effects of a proton-pump inhibitor in cystic fibrosis.
AB  - Most children with cystic fibrosis (CF) show persisting steatorrhoea even when
      treated with pancreatic enzyme. As a low duodenal pH could be responsible for
      this persisting fat loss, we evaluated the effects of a proton-pump inhibitor
      (lansoprazole) on both steatorrhoea and growth parameters in 15 CF patients, aged
      3.1-22.6 y. Acid steatocrit, anthropometry and dual-energy X-ray absorptiometry
      were used to evaluate steatorrhoea and the nutritional status before, during and
      3 months after stopping lansoprazole treatment (15 mg/d for 3 months). Mean +/-
      SD acid steatocrit values decreased from 37.1 +/- 8.8% to 28.5 +/- 10.6% (p =
      0.02). Significant mean Z-score improvements were found for weight (+0.14; p =
      0.02), height (+0.15; p = 0.03), subscapular (+0.61; p = 0.003), supra-iliac
      (+0.8; p = 0.002) and the sum of the four measured skinfolds (+0.61; p = 0.002).
      Z-scores deteriorated again after stopping lansoprazole. Fat mass and bone
      mineral content increased significantly on lansoprazole (p = 0.008 and p = 0.005,
      respectively). We conclude that lansoprazole as adjuvant therapy significantly
      improves both steatorrhoea and the nutritional status in CF children who maintain
      steatorrhoea while on pancreatic enzymes.

PMID- 9641740
TI  - Serum inflammatory markers and effects of age and tobacco smoke exposure in young
      non-asthmatic children.
AB  - Serum eosinophil cationic protein (ECP), but not serum myeloperoxidase (MPO), has
      been found to reflect disease activity of asthma and eczema, but no reference
      values exist for young children. Thus, we aimed to provide values of serum-ECP
      and serum-MPO in young children without obstructive airways disease (OAD), and
      determine possible influencing factors. Parental interview was performed and
      serum was collected from a total of 245 children (207 children aged 24-41 months
      and 76 children aged 0-23 months) with no history of lower respiratory disease.
      Repeated serum samples were obtained in 38 subjects. Ten percent of the children
      had active eczema at examination. All children were controls in the "Environment
      and Childhood Asthma" study in Oslo. Geometric means (GM +/- 1.96 SD) for serum
      ECP were 11.8 microg/l (2.5-56.0) and 7.9 microg/l (2.0-30.4), respectively, in
      the 0-23 and 24-41-month-old children, with the corresponding values for serum
      MPO 453 microg/l (153-1349) and 347 microg/l (142-859), respectively. Age was
      inversely associated with serum-ECP and serum-MPO, most pronounced in the
      youngest children. Active eczema and maternal daily smoking adversely affected
      serum-ECP, but not serum-MPO. Gender and parental atopy did not influence the
      results. We conclude that serum-ECP in very young children is influenced by age
      and active eczema and is related to maternal smoking in a dose-dependent fashion.
      These factors should be considered when assessing inflammatory markers in very
      young children.

PMID- 9641741
TI  - Factors affecting cognitive, motor, behavioral and executive functioning in
      children with phenylketonuria.
AB  - We administered measures of cognitive, frontal lobe (executive), behavioral and
      motor functioning to 18 children with classical phenylketonuria, aged 12-101
      months, in order to determine the relationship of age, current and lifetime
      average phenylalanine levels, and individual variation (standard deviation of
      lifetime average levels) to these functions. On measures of cognitive function,
      in children > or = 3 y of age lower current phenylalanine levels were associated
      with higher cognitive functioning. On a behavioral temperament scale designed for
      normal children, we found that higher current and average phenylalanine levels
      correlated with more difficult temperament. Motor function was also poorer in
      children with phenylketonuria, and was most impaired in children with current
      phenylalanine levels >360 micromol/l. We also identified a previously unreported
      correlation between increased individual variation and poorer executive function
      performance, a finding that may raise new management concerns about level
      fluctuations. Maintenance of phenylalanine levels <360 micromol/l may be
      necessary for optimal performance in children with phenylketonuria.

PMID- 9641742
TI  - Molecular genetics of nocturnal enuresis: clinical and genetic heterogeneity.
AB  - Forty-two children with nocturnal enuresis (27 with primary, 4 with secondary
      nocturnal enuresis and 11 with combined primary nocturnal enuresis and daytime
      wetting) were selected retrospectively from a study of 167 consecutive children
      with enuresis. The aim of the study was to collect formal genetic data, perform
      molecular genetic linkage-analyses with five microsatellite markers on
      chromosomes 13q, 12q or 8q and specify the associations between genetic findings
      and clinical, as well as psychiatric diagnoses. Positive linkage of nocturnal
      enuresis to one of the microsatellite markers was possible in 27 children from 23
      families and was not possible in 15 children. Somatic findings in both the groups
      with and without possible assignment of nocturnal enuresis to a marker were
      heterogeneous. Psychiatrically, a low rate of behavioural problems was apparent.
      These findings support the hypothesis of genetic and phenotypical heterogeneity
      of nocturnal enuresis, without linkage of specific psychiatric and somatic
      phenotypes to certain chromosome markers.

PMID- 9641743
TI  - Disease of the liver following bone marrow transplantation in children:
      incidence, clinical course and outcome in a long-term perspective.
AB  - Sixty-four consecutive cases of allogeneic (n = 16), autologous (n = 47) or
      syngeneic (n = 1) bone marrow transplantation (BMT) in children with
      haematological or lymphoid malignancy, aplasia or metabolic disease were reviewed
      to assess the incidence, clinical presentation and outcome of liver disease.
      Median follow-up time was 5 y (1.0-10). No liver diagnosis was established at the
      pre-transplant check-up. During the first 100 d post-transplant, 81% of the
      patients had impaired liver function as documented by various biochemical
      parameters. Three of 64 patients (5%) met diagnostic criteria for veno-occlusive
      disease. Four (25%) of the 16 receiving allografts were diagnosed as having acute
      graft vs host disease (GVHD) with liver involvement (grades II-III). No patient
      died of liver disease. During the late post-transplant follow-up, one patient
      developed HCV hepatitis after packed erythrocyte transfusion. Four patients were
      diagnosed as having chronic GVHD with liver involvement; three of them also had
      an episode of CMV hepatitis. At their latest follow-up, the patients with chronic
      GVHD had aminotransferase values 1.5-3 times the normal, whereas all other long
      term survivors had normal or near-normal liver function tests. We conclude that
      the incidence of serious liver disease was low in this paediatric population of
      bone marrow recipients.

PMID- 9641744
TI  - Foetal supraventricular tachycardia treated with sotalol.
AB  - This retrospective study (1991-95) presents our experience with sotalol in the
      treatment of 14 foetuses with supraventricular tachycardia (SVT). SVT was
      diagnosed in a structurally normal heart at a gestational age of 24-35 (median
      28) weeks. In eight foetuses, hydrops was evident at presentation. In all
      patients pharmacological conversion with digoxin was tried before sotalol
      treatment was started. Sotalol was given orally to the mothers in a dose of 80
      160 mg x 2. Cardioversion was obtained in 10 foetuses. In seven of these patients
      re-entry tachycardia and in five pre-excitation could be documented after birth.
      In two foetuses not responding to sotalol a long RP tachycardia was demonstrated;
      even when using digoxin, sotalol, flecainide and/or propafenone in different
      combinations after birth complete suppression of the arrhythmia was not obtained.
      Two severely hydropic foetuses died 1 and 10 d, respectively, after starting with
      sotalol. The 12 surviving infants were doing well except for one infant, with a
      cerebral lesion probably related to the arrhythmia. These findings demonstrate
      that sotalol can be useful in the treatment of foetal SVT.

PMID- 9641745
TI  - Arachidonic acid metabolites in CSF in hypoxic-ischaemic encephalopathy of
      newborn infants.
AB  - The aim of this study was to evaluate the cerebral synthesis of eicosanoids in
      the asphyctic newborn and to investigate the relation between the prostanoid
      profiles in cerebrospinal fluid (CSF) and the appearance and severity of hypoxic
      ischaemic encephalopathy (HIE). Levels of 6-keto-PGF(1-alpha), TXB2, PGE2 and
      PGF(2-alpha), in CSF were measured in 40 full term newborns during the first day
      of life. Thirty of these newborns had birth asphyxia and were divided into three
      groups: 10 without HIE, 12 with mild HIE and 8 with moderate-severe HIE. They
      were compared to a control group of 10 non-hypoxic newborns. Determinations of
      the metabolites in CSF were performed by RIA and expressed as pg/ml (mean +/-
      SD). The CSF TXB2 (thromboxane A2 metabolite) in asphyxiated newborns was always
      higher than in the control group (28.12 +/- 10.6), and related to the severity of
      HIE (p = 0.005): without HIE (50.84 +/- 16.4; p = 0.02), mild HIE (80.65 +/-
      12.64; p < 0.01) and moderate-severe HIE (178.14 +/- 20.5; p < 0.01). The CSF 6
      keto-PGF(1-alpha) (prostacyclin metabolite) in asphyxiated newborns was always
      higher than in the control group (80.55 +/- 12.56), but indirectly related to the
      severity of HIE: without HIE (240.95 +/- 28.12; p < 0.01), mild HIE (183.65 +/-
      30.1; p < 0.01) and moderate-severe HIE (140.55 +/- 25.12; p < 0.01). In the
      moderate-severe HIE group, the increase in TXB2 was higher than the rise in 6
      keto-PGF(1-alpha).

PMID- 9641746
TI  - Bacterial genotype and neurological complications of Escherichia coli O157:H7
      associated haemolytic uraemic syndrome.
AB  - We examined the possibility of an association between the bacterial genotype of
      Escherichia coli O157:H7 and the likelihood of progression to neurological
      complications in childhood gastroenteritis-associated haemolytic uraemic syndrome
      (D+HUS). Bacterial stool isolates were available from 51 patients with HUS; 11 of
      these patients suffered a neurological complication. Bacteria were assessed for
      plasmid content, verotoxin (Shiga-like toxin) profile, verotoxin 2 subtype, and
      presence of the eaeA (effacement and attachment) marker. No association of
      bacterial genotype with central nervous system (CNS) manifestations was observed.
      Whilst the cause of CNS manifestations may be multifactorial, there is no
      evidence at present to implicate specific bacterial traits.

PMID- 9641747
TI  - Prevention of hypoglycaemia in a patient with type Ib glycogen storage disease by
      an amylase (alpha-glucosidase) inhibitor.
AB  - Patients with type Ib glycogen storage disease (GSD Ib) are susceptible to
      hypoglycaemic episodes. To determine whether an amylase (alpha-glucosidase)
      inhibitor, voglibose, can be useful in the control of hypoglycaemia, we tried it
      in a 14-y-old male with GSD Ib. Oral administration of voglibose prolonged the
      duration of normoglycaemia and reduced the incidence of hypoglycaemia attacks.
      These findings indicate that voglibose may be useful for preventing hypoglycaemia
      in GSD Ib patients.

PMID- 9641748
TI  - Optic neuropathy in McCune-Albright syndrome: an indication for aggressive
      treatment.
AB  - McCune-Albright syndrome consists of the triad polyostotic fibrous dysplasia,
      cafe-au-lait spots and autonomous hyperfunction of one or more endocrine systems.
      The most frequent neurological complication of craniofacial fibrous dysplasia is
      visual loss. We describe a 17-y-old boy with McCune-Albright syndrome and acute
      loss of vision in the left eye caused by encroachment of the left optic nerve by
      fibrous dysplastic lesions. Neurosurgical intervention improved left eye vision.
      Aggressive intervention is indicated in cases of acute visual loss in patients
      with craniofacial fibrous dysplasia. This is supported by a review of other
      reported cases.

PMID- 9641749
TI  - Factitious illness by proxy presenting as anorexia and polydipsia by proxy.
AB  - Factitious illness by proxy is a highly pathological form of parent-child
      relationship. To our knowledge no former case of polydipsia by proxy has been
      published. The case of a 2-y-old boy suffering from malnutrition due to
      displacement of maternal anorexia and polydipsia is presented. Child psychiatric
      evaluation found cognitive delay and psycho-social impairment in the child, as
      well as a severe mother-child relationship disturbance. Psychological assessment
      showed a personality disorder with depressive and paranoid features in the
      mother. The father was described as a schizoid personality. The possible
      mechanisms of displacement are hypothesized.

PMID- 9641750
TI  - Colchicine for recurrent pericarditis in children.
AB  - The incidence of recurrence of acute pericarditis in children varies from 15% to
      30% and is accompanied by a high morbidity. Various treatment modalities have
      been used with variable success rates and side effects. La Serna et al. (Lancet
      1987; 26: 1517) were the first to treat adults with recurrent pericarditis with
      colchicine, and were followed by other authors. To our knowledge no studies in
      children have been reported. In this paper, we present three children who
      suffered from viral or idiopathic recurrent pericarditis, despite multiple
      courses of non-steroidal anti-inflammatory drugs (NSAIDs) and/or corticosteroids.
      They responded remarkably well to colchicine, which was administered for 6 months
      with no adverse reactions. They continue to do well 18, 11 and 12 months after
      cessation of treatment, respectively.

PMID- 9641751
TI  - Serial chitotriosidase activity estimations in neonatal systemic candidiasis.

PMID- 9641752
TI  - Serum malondialdehyde levels in preterm and fullterm infants undergoing
      phototherapy.

PMID- 9641792
TI  - 'Biological signals' to 'biological signals and receptors'.

PMID- 9641793
TI  - Hypothalamic relationships between interleukin-6 and LHRH release affected by
      bacterial endotoxin in adult male rats. Involvement of the inhibitory amino acid
      system.
AB  - Immune system alterations coexist with modifications in the reproductive axis.
      The bacterial endotoxin lipopolysaccharide (LPS) has inflammatory effects and
      stimulates cytokine release in the hypothalamus where LHRH neurons are located.
      LPS inhibition of LHRH release at hypothalamic level appears to be associated
      with modifications in the cerebral immune system. Central and peripheral LPS
      administration induces the expression and release of several cytokines in the
      central nervous system. Hence the present study was designed to investigate a
      possible function of the interleukin-6 (IL-6) stimulated by LPS in the regulation
      of LHRH secretion. Male rats were decapitated, and the preoptic mediobasal
      hypothalamic area (PO/MBH) was dissected and superfused with Earle's balanced
      salt solution. Superfusate fractions were collected at 15-min intervals after a
      60-min stabilization superfusion period. LPS (100 ng/ml) and IL-6 receptor
      antagonist (IL-6ra) were then added to the superfusion medium over 1 h in two
      different experimental designs: (1) LPS only and (2) LPS followed by IL-6ra,
      performed in different experiments. This was followed by a washout period. The
      PO/MBH fragments were then subjected to a 56 mM K+ stimulus. Control PO/MBH
      fragments were continuously superfused with Earle's solution. As expected, LHRH
      release was significantly reduced (p < 0.05) during and following exposure to
      LPS. At the same time, IL-6 concentrations significantly increased in the
      superfusion medium compared with the control group. IL-6ra significantly (p <
      0.01) potentiated the inhibitory effect of LPS on LHRH secretion. On the bases of
      previous papers indicating a stimulatory effect of IL-6 on LHRH release it could
      be considered that the potentiation of IL-6ra of the inhibitory effect of LPS on
      LHRH could be the consequence of the lack of the stimulatory effect of IL-6 on
      LHRH produced by the receptor antagonist. IL-6ra also increased IL-6 levels
      measured in medium probably due to a decrease in the metabolization induced by
      the blockage of the receptors and the consequent accumulation of IL-6 in the
      media. These results could indicate that IL-6 partly attenuates the inhibitory
      effect of LPS on LHRH release. These observations indicate that there is an
      increase in IL-6 release that becomes significant at the same time when LHRH
      release is decreased. Also, depolarizing concentrations of K+ (56 mM) did not
      increase IL-6 release, while LHRH release from the hypothalamic fragments was
      significantly increased. These data suggest that the inhibitory effect of LPS on
      LHRH release may be explained by the stimulation of other cytokines than IL-6,
      meanwhile the augmented levels of IL-6 probably released via a nonneuronal source
      was shown to be higher when LHRH was decreased. This could confirm the
      stimulatory role of IL-6 on LHRH release.

PMID- 9641794
TI  - Circadian rhythms in adenohypophysial hormone levels and hypothalamic monoamine
      turnover in mycobacterial-adjuvant-injected rats.
AB  - The effect of Freund's adjuvant injection on 24-hour variation in circulating
      ACTH, prolactin, growth hormone (GH) and thyroid-stimulating hormone (TSH)
      levels, and of hypothalamic norepinephrine (NE) content and dopamine (DA) and
      serotonin (5HT) turnover was examined in adult rats. In control rats, serum ACTH
      and prolactin exhibited peak values at the light-dark transition while the
      maximum in TSH was found in the late afternoon. GH levels did not vary on a 24
      hour basis. In Freund's-adjuvant-injected rats, 24-hour variations in TSH levels
      became blunted while 24-hour variations in prolactin and ACTH persisted. Freund's
      adjuvant treatment augmented serum ACTH and prolactin levels, and decreased GH
      and TSH levels. Hypothalamic NE content, and turnover of DA and 5HT varied on a
      24-hour basis in rats receiving adjuvant's vehicle. The NE content of the
      anterior, medial and posterior hypothalamus peaked at 04.00 h, while that of the
      median eminence attained its maximum at 16.00-20.00 h. Maxima in hypothalamic DA
      and 5HT turnover occurred at 04.00 h regardless of the region examined. In
      Freund's-adjuvant-injected rats, reduced amplitude of daily variations of NE
      content in the median eminence and anterior and medial hypothalamus, as well as a
      phase advance in the 24-hour rhythm of the posterior hypothalamic NE content were
      seen. Mycobacterial adjuvant injection also reduced the amplitude of circadian
      rhythm in hypothalamic 5HT turnover, shifted the maximum in median eminence DA
      turnover towards light-dark transition, and decreased the amplitude of DA
      turnover rhythm in the anterior, medial and posterior hypothalamus.
      Administration of the immunosuppressant drug cyclosporine restored the augmented
      ACTH and prolactin levels and the depressed GH and TSH levels found in Freund's
      adjuvant-injected rats. Cyclosporine was also effective to restore 24-hour
      rhythmicity of serum ACTH and TSH, but not of prolactin levels. Immunosuppression
      restored rhythmicity of NE content and of DA and 5HT turnover in anterior, medial
      and posterior hypothalamic regions. Cyclosporine did not modify the effect of
      Freund's adjuvant on median eminence but in was able to counteract the changes in
      the DA and 5HT turnover in the median eminence found after immunization. The
      results are in accord with a significant effect of immune-mediated inflammatory
      response at an early phase after Freund's adjuvant injection on ACTH, GH,
      prolactin and TSH release mechanisms, which was partially sensitive to
      immunosuppression induced by cyclosporine.

PMID- 9641795
TI  - Acute and chronic effects of superior cervical ganglionectomy on in vitro
      mitogenic responses of lymphocytes from submaxillary lymph nodes of pituitary
      grafted rats.
AB  - Male rats were grafted an anterior pituitary within breast muscles or received a
      sham operation on day 5 of life. At the 60th day of life, the sympathetic
      denervation of rat submaxillary lymph nodes was achieved by a bilateral
      sympathetic superior cervical ganglionectomy (SCGx; at 15.00 h). Rats were killed
      either 18 h later (acute SCGx) or after 12 days (chronic SCGx) to measure
      lipopolysaccharide (LPS)- and concanavalin A (ConA)-induced cell proliferation in
      submaxillary lymph nodes, submaxillary lymph node cellularity and serum prolactin
      levels. In control rats, acute SCGx significantly augmented LPS or ConA activity
      on lymph cells while chronic SCGx had no effect. In pituitary-grafted rats, acute
      SCGx depressed the mitogenic effect of LPS or ConA whereas chronic SCGx augmented
      it. A global inhibitory effect of surgical stress on submaxillary lymph node
      cellularity was found in rats subjected to SCGx or its sham operation 18 h
      earlier. Serum prolactin levels increased significantly in pituitary-grafted
      rats, particularly in those subjected to chronic SCGx. In pituitary-grafted rats,
      a significant effect of acute SCGx was apparent, with serum prolactin levels
      augmenting about twice in sham-SCGx rats, and to a significantly less extent in
      acute SCGx rats. The results provide further evidence of the immunomodulatory
      role of local sympathetic nerves in submaxillary lymph nodes.

PMID- 9641796
TI  - Cytokine-neurotransmitter interactions in the brain.
AB  - The data reviewed in this study show that immune-active molecules, such as
      infectious agents and their components, and cytokines, may induce profound
      alterations in several neurotransmitters in the CNS. The activation of the immune
      system elicits fever, behavioral and neuroendocrine changes and may be involved
      in neuropathological changes occurring in CNS conditions. These effects may be
      achieved through and accounted for by the changes induced in central
      neurotransmitters and in the neuroendocrine system by immune challenges. The
      present review will summarize the available evidence of the reciprocal
      interactions between cytokines and neurotransmitters in the CNS.

PMID- 9641797
TI  - Cytokines and cognitive function in mice.
AB  - A bidirectional flow of informations exists between the central nervous system
      and the immune system. Cytokines play a crucial role in this communication and
      exert several neuromodulatory actions. This short review considers some data
      concerning the effects of several cytokines, interleukin (IL)-1, IL-2, IL-6 and
      granulocyte-macrophage colony-stimulating factor on scopolamine-induced amnesia
      for a passive avoidance response, and on hippocampal neurotransmitter amino acid
      levels in mice. We interpret these behavioral and biochemical observations to
      indicate that the cytokine-to-brain communication can result in alterations in
      brain functions.

PMID- 9641798
TI  - Mechanism of action of interleukin-1 in modulating gonadotropin secretion. In
      vivo and in vitro studies.
AB  - To obtain further information on the mode of action of interleukin (IL)-1 in
      modulating gonadotropin secretion, a series of in vivo and in vitro studies has
      been performed with the beta-isoform of IL-1. IL-1 beta injected in a lateral
      ventricle of 3-week-castrated female rats resulted in the expected decrease in
      serum levels of gonadotropins luteinizing hormone (LH), and follicle-stimulating
      hormone (FSH), accompanied by a decrease in the number of LH-releasing hormone
      (LHRH) receptors. These results may indicate that the inhibition of gonadotropin
      release may result from a decrease in the number of LHRH pituitary receptors
      either through a direct effect on the pituitary or by modulating the release of
      LHRH from hypothalamic neurons able to induce a reduction in pituitary LHRH
      receptors. In vitro studies using the GT1-1 cell line, which specifically
      produces and secretes LHRH, demonstrated that IL-beta stimulates LHRH release but
      does not influence intracellular levels of LHRH mRNA. These results seem to
      indicate that IL-1 beta may act at several levels of the nervous machinery
      leading to gonadotropin secretion, with a series of effects more complex than
      previously anticipated.

PMID- 9641800
TI  - Combining ECT and antidepressants: time to reassess.

PMID- 9641799
TI  - Melatonin involvement in immunity and cancer.
AB  - The most studied endocrine product of the pineal gland, melatonin, has been
      reported to be involved in the feedback between neuroendocrine and immune
      functions and to exert oncostatic action, at least in certain experimental
      conditions. Melatonin seems to be an integral part of the immune system, by
      exerting direct and/or indirect stimulatory effects on both cellular and humoral
      immunity. Likewise, an antitumor activity of melatonin has been shown in several
      experimental models in vivo and in vitro. The means by which melatonin exerts its
      effects on immunity and neoplastic growth have not been elucidated. The different
      putative mechanisms of action of melatonin investigated so far are here briefly
      discussed.

PMID- 9641802
TI  - A comparison of visual and computer-generated measures of "seizure quality".
AB  - We report on the first direct comparison of measures of seizure quality generated
      by visual rating of electroencephalographic (EEG) regularity and postictal
      suppression with THYMATRON-DGx computer-generated indices of seizure energy and
      postictal suppression. Thirty-two consecutive patients referred for
      electroconvulsive therapy (166 consecutive treatments) were studied. Blinded
      ratings of seizure duration, regularity, and postictal EEG amplitude suppression
      derived from the paper EEG were compared against computer-rated measures of
      seizure duration, seizure energy index, mean ictal amplitude, and postictal
      suppression. Our results confirm previous findings of high correlations between
      computer and visual determinations of seizure duration. Significant differences
      were found for computer-derived postictal suppression, seizure energy index and
      mean ictal amplitude for different levels of the visual rating scales. Our
      results provide preliminary support for the concurrent validity of these
      measures.

PMID- 9641801
TI  - A comparison of brief and ultrabrief pulse stimuli in unilateral ECT.
AB  - A double-blind, randomized, comparative study of the therapeutic efficacy and
      side effects of unilateral electroconvulsive therapy (ECT) given with two
      different stimulus types was carried out in the Kuffner Sanatorium, Horni
      Berkovice, Czech Republic. Brief or ultrabrief pulse stimuli were used in 48
      hospitalized patients, ages 17-61 years, diagnosed with either schizophrenia (n =
      42) or major depression (n = 6). All patients received eight unilateral
      treatments each. Their clinical state and presence of cognitive impairment were
      evaluated with a battery of tests and rating scales before ECT, after the last
      ECT, and 1 month later. Patients were markedly improved after the course of ECT,
      and the improvement was maintained 1 month later. There were no significant
      differences in the extent of improvement between the groups treated with brief-
      and ultrabrief-pulse stimuli. No deleterious effects on cognitive functions and
      memory were detected. In fact, there was a trend toward improvement in memory and
      other cognitive functions after ECT in both groups, with no significant
      difference between them. The two stimulus waveforms studied (brief and ultrabrief
      pulse) thus appear to be equally effective and free of deleterious effects on
      memory and cognition. The response in schizophrenic patients was remarkable and
      deserving of further study.

PMID- 9641803
TI  - Attenuation of ECS-induced retrograde amnesia by using an herbal formulation.
AB  - Earlier research indicated the efficacy of a complex herbal formulation in the
      attenuation of electroconvulsive shock (ECS)-induced amnestic deficits in rats;
      this study sought to ascertain whether a simplified herbal formulation (Memorin;
      Phyto-Pharma, India) also was effective. Rats pretreated for a fortnight with
      Memorin (200 mg/kg/day) or vehicle were exposed to a passive-avoidance learning
      paradigm in a shuttle box. The next day, the rats were administered two true or
      sham ECSs, 5 h apart; recall of the pre-ECS learning was reassessed on the
      following day. ECS was found to produce significant retrograde amnesia (p <
      0.002). Memorin attenuated the ECS-induced amnesia (p = 0.00003) without
      influencing the ECS seizure duration. The clinical implications of these findings
      are discussed.

PMID- 9641804
TI  - Anesthetic induction for ECT with etomidate is associated with longer seizure
      duration than thiopentone.
AB  - Many factors influence seizure duration associated with electroconvulsive therapy
      (ECT). This is a chart review study to assess seizure duration measured with both
      electroencephalography and electromyography after anesthetic induction with
      either thiopentone or etomidate. Thirty-seven patients receiving ECT for
      depression were entered into the study, and a pair of seizures was measured from
      each patient. Alternate induction agents were used in sequential pairings, and
      the study was controlled for interval between seizures, laterality, and percent
      energy. Etomidate was associated with a significantly (p = 0.0002, F = 15.84, df
      = 1, analysis of variance) longer seizure duration (mean = 34.43 s, SD = 16.06)
      than thiopentone (mean = 21.73 s, SD = 9.33).

PMID- 9641805
TI  - Acute post-ECT cardiovascular response: a comparison of threshold right
      unilateral and bilateral ECT.
AB  - The effect of electrode placement on cardiovascular responses was studied. Rate
      pressure product and diastolic blood pressure before anesthesia and 30 s after
      electroconvulsive therapy (ECT) seizure were recorded. Recordings were made at
      the first (threshold ECT) session in 124 bilateral ECT (BLECT) and 95 unilateral
      ECT (ULECT) consenting patients. Postictal rate pressure product (RPP) was
      significantly higher after BLECT than ULECT. Mean increase in RPP from pre- to
      postictal phase was 31% in the former. The corresponding change with ULECT (20%)
      was significantly smaller. In the stepwise, multiple regression model, pre-ECT
      RPP, age, and stimulus laterality significantly contributed to postictal RPP. No
      cardiovascular complications occurred in any of the 219 ECT sessions.

PMID- 9641806
TI  - Propofol anesthesia, seizure duration, and ECT: a case report and literature
      review.
AB  - Propofol is a nonbarbiturate anesthetic induction agent known to have anti
      convulsant properties. When used as an anesthetic for electroconvulsive therapy
      (ECT), it can reduce seizure duration to a significant degree, which may not be
      fully appreciated. A case is presented in which propofol caused a 63.1% reduction
      in mean seizure duration compared with preceding and subsequent treatments with
      thiopental anesthesia. The literature on the use of propofol for ECT was reviewed
      with specific reference to its effect on seizure duration and any evidence of
      superiority to the barbiturate induction agents. It is concluded that propofol
      may have only very circumscribed indications as an anesthetic for ECT. If used,
      psychiatrists and anesthetists must be aware of its potency as an anticonvulsant.

PMID- 9641807
TI  - Ventricular tachycardia with ECT.
AB  - A case is presented in which a patient with ischemic heart disease developed
      episodic, nonsustained ventricular tachycardia (VT) during electroconvulsive
      therapy for major depression. The VT had a frequency of 200 beats/min and ceased
      spontaneously after 17 s. Altered autonomic discharge in the presence of ischemia
      is the probable cause. Predisposing factors, as well as management
      considerations, are discussed.

PMID- 9641808
TI  - Electroconvulsive therapy in patients with long bone fractures.
AB  - Two elderly patients with severe depression were treated with electroconvulsive
      therapy despite long bone fractures. Good liaison was maintained throughout with
      the orthopaedic surgeons and anaesthetists. Both of the patients improved
      significantly, and there were no musculoskeletal complications.

PMID- 9641809
TI  - Duration of liquid fast before ECT.

PMID- 9641810
TI  - Prolonged seizures in the young.

PMID- 9641811
TI  - ECT in the presence of a cerebral aneurysm.

PMID- 9641812
TI  - ECT with implantable cardioverter defibrillator.

PMID- 9641813
TI  - Junior doctors' training in the theory and the practice of electroconvulsive
      therapy.
AB  - Recent advances in knowledge about effective administration of electroconvulsive
      therapy (ECT) has placed great emphasis on the importance of good training and
      supervision of those administering it. The American Psychiatric Association
      requires that doctors be specifically accredited before they are allowed to give
      ECT. In England and Wales training is much more informal and ECT is often given
      by junior doctors. Doctors rostered to administer ECT in Wales and in two areas
      of England were surveyed as part of the College's third audit of ECT. About two
      thirds of respondents were at senior house officer level. The training in ECT
      appeared of variable quality and one-half had not been supervised by an
      experienced psychiatrist on the first occasion they administered ECT. Responses
      to exam-type questions revealed that 45% lacked knowledge about one or more basic
      issue related to effective administration of ECT.

PMID- 9641814
TI  - [Significance of ICH--toxicokinetics guidance and its practice--a useful approach
      for safety drug development].
AB  - In the International Conference on Harmonization (ICH), "Note for Guidance on
      Toxicokinetics: the Assessment of Systemic Exposure in Toxicity Studies (ICH
      Harmonized Tripartite Guideline)" was signed off in October 1994 by 6 parties of
      Japan, EU and the United States. The Ministry of Health and Welfare, Japan, has
      issued the notification "Upon the Guidance for Toxicokinetics (Assessment of
      Systemic Exposure in Toxicity Studies)" (Yakushin No. 443 dated July 2, 1996).
      The notification stated that pivotal toxicity study which initiates on and after
      January 1st, 1997 should includes appropriate Toxicokinetic study. In the ICH
      Guidance for pharmaceuticals, TK is defined as the generation of pharmacokinetic
      data, either as an integral component in the conduct of non-clinical toxicity
      studies or in specially designed supportive studies, in order to assess systemic
      exposure. These data may be used in the interpretation of toxicology findings and
      their relevance to clinical safety issues. TK study is considered to be
      indispensable for safety assessment, and thus should be conducted in compliance
      with the GLP regulations. The ICH guidance also emphasizes that the exposure
      assessment in individual toxicity studies should be based on a flexible and step
      by step and a case by case decision making process. In this review article, the
      background for the introduction of this TK Guidance, the outline of the ICH-TK
      Guidance, the definition and fundamental principles of the ICH-TK, and its
      toxicological significance and practical problems in the conduct of TK study are
      described.

PMID- 9641815
TI  - [Building information infrastructure at research institutions that support health
      hazard control].
AB  - In recent years the Ministry of Health and Welfare (MHW) encountered large scale
      health hazards and medicare incidents that required flexible, intersectional, and
      dynamic responses. Both research institutions under the MHW and their researchers
      got involved in project teams which were organized in order to cope these hazards
      and incidents. However it might be more effective if some information
      infrastructure for hazard control is built as one component of the MHW hazard
      management system. In this paper the design concept and implementation for such
      information infrastructure were discussed. The infrastructure consists of
      computer networks and systems which are based on the Internet and the related
      technologies such as WWW.

PMID- 9641816
TI  - [Modulations of human growth hormone receptor level on the cell surface].
AB  - Using a monoclonal antibody (GHRP2-88) raised against the extracellular portion
      of human growth hormone receptor (hGHR), the mechanisms on modulations of
      cellular levels of hGHR were investigated in human IM-9 cells. Upon stimulation
      with human growth hormone (hGH), hGHRs on the cell surface are down-regulated
      through internalization and degradation of hGHR. For hGHR internalization, hGH
      mediated dimerization of hGHRs, but not staurosporine-sensitive phosphorylation
      is required. For hGHR degradation, however, staurosporine-sensitive
      phosphorylation is necessary. In the absence of hGH, hGHRs on the cell surface
      are cleaved to release human growth hormone-binding proteins (hGH-BPs), probably
      by a metalloprotease. In the presence of hGH, the hGH-BP release was rather
      decreased based on the reduction in cell surface hGHRs. Thus, the cell surface
      level of hGHR may be regulated post-translationally by the two mechanisms
      depending on the external hGH levels.

PMID- 9641817
TI  - [Study of N-nitroso compounds which have NO-release ability].
AB  - Nitric oxide (NO), which plays an important role in the vital functions of
      organisms, is gaseous and labile molecule. Much attention has been paid to the
      stability and easily handling of NO donors, for careful handling of NO is
      required during experimental work. We synthesized a series of aromatic N
      nitrosoureas and N-nitrosamides which efficiently liberates NO at room
      temperature. Generation of NO from the aromatic N-nitroso compounds was
      chemically confirmed by the trapping of NO as a nitrosyl complex of
      tetraphenylporphyrinatocobalt (II) and spectrophotometrically quantified by means
      of the Griess reaction using a newly designed test apparatus. 3,3-Dibenzyl-1-(4
      tolyl)-1-nitrosourea showed the greatest NO-generating ability among the
      synthesized N-nitroso compounds. Further, the NO-generating ability was related
      to the reciprocal of the ID50 value for growth inhibition of cultured L-5178Y
      cell by the aromatic N-nitroso compounds.

PMID- 9641818
TI  - [Purinoceptor-induced cytoplasmic calcium oscillation in megakaryocytes].
AB  - Megakaryocytes isolated from rat bone marrow respond to externally applied ATP
      and ADP, showing a periodic K+ current that reflects oscillation in cytoplasmic
      calcium concentration. The agonist selectivity of the purinoceptor on the
      megakaryocyte is unique. In addition, the intracellular mechanism of calcium
      oscillation and the effects of many modulating factors were investigated.

PMID- 9641819
TI  - [Oxidation and reduction of nitroarene as environmental mutagens].
AB  - Newly synthesized dinitrobenzo[a]pyrenes and 6-aza analogues of 1- and 3
      nitrobenzo[a]pyrenes showed strong mutagenic activity in Salmonella assays (TA98
      and TA98NR). Nitroreduction is essential for metabolic activation of nitroarene.
      The structure activity relationships of mono-, di- and trinitrophenanthrene were
      studied. Electrochemical ease of nitroreduction and dihedral angles of nitro
      substituents to aromatic rings is found to be important factor to determine their
      mutagenic potency. Nitroarene is oxidatively metabolized to form hydroxylated and
      nitrosubstituted derivatives and the same oxidative products were obtained by the
      reaction of nitroarene with chemically generated superoxide anion radical,
      suggesting the participation of superoxide in metabolic oxidation of nitroarene.
      Catalytic activity of nitroarene as a mediator in the reductive activation of
      molecular oxygen was also evaluated by using potential step chronocoulometry
      method. The potential relevence of toxicity caused by redox cycling could be
      solved by using this method.

PMID- 9641820
TI  - [Studies on the stability of 89 pesticides in organic solvent].
AB  - The stability of 89 pesticides (17 organochlorine, 33 organophosphorus, 8
      pyrethroid, 12 carbamate, and 19 other pesticides) in 6 kinds of organic solvents
      (methanol, ethanol, 2-propanol, ethyl acetate, n-hexane, and acetone) was
      investigated using gas chromatography/mass spectrometry (GC/MS). All of the
      investigated pesticides were stable in all of the tested organic solvents during
      storage for 6 hours at room temperature in the dark except captafol, captan,
      phosmet, chinomethionat, and dicofol. However, the decreases of captafol, captan,
      phosmet, and chinomethionat were observed in methanol. The decreases of captafol,
      captan, and phosmet were also observed in ethanol. Moreover, the decrease of
      dicofol was observed in acetone. The decrease of captafol dissolved in methanol
      at a concentration of 2 micrograms/ml was faster than those of captan, phosmet,
      and chinomethionat; the residual captafol was 75% after 30 min of storage.
      Dicofol dissolved in acetone also decreased during storage in a refrigerator.
      4,4'-dichlorobenzophenone (DCBP) and chlorobutanol were detected in the acetone
      solution of dicofol after storage. Furthermore, it was found that dicofol was
      decomposed by acetone at an injection port, and DCBP and chlorobutanol were
      formed when it was injected into GC with acetone.

PMID- 9641821
TI  - [A 13-week subchronic oral toxicity study of carob germ colour in F344 rats].
AB  - A13-week subchronic oral toxicity study of carob germ colour, one of natural
      colour additives was carried out in F344 rats at dose levels of 5.0, 1.7, 0.6,
      0.2 and 0% in the powdered diet. Rats were randomly allocated to 5 groups, each
      consisting of 10 males and 10 females. No animals died during the experiment and
      no changes in body weights and food intakes were observed in any dosed groups.
      Changes indicating obvious toxicity of carob germ colour were not observed in the
      organ weights, hematological, serum biochemical and histopathological
      examinations. These findings indicate that the treatment of 5% carob germ colour
      in diet for 13 weeks did not cause any significant toxicity in rat.

PMID- 9641823
TI  - [Effects of 16-week dietary administration of 2-amino-3,8-dimethylimidazo[4, 5
      f]quinoxaline in rats].
AB  - 2-Amino-3,8-dimethylimidazo[4, 5-f]quinoxaline (MeIQx), a heterocyclic amine
      found in cooked meats, is carcinogenic in mice and rats at high doses. In order
      to examine the toxicity including preneoplastic changes at the lower doses, a
      total of 170 male Fischer 344 rats were administered MeIQx for 16 weeks at a dose
      of 100, 10, 1, 0.1, 0.01, 0.001 ppm or 0 ppm in the diet. The numbers of GST-P
      positive foci and BrdU-labeling indices in the liver were significantly increased
      by the dietary administration of 10 ppm and 1 ppm or more of MeIQx respectively,
      when compared with the basal diet-fed control rats. Aberrant cry p tfoci (ACF)
      were also significantly increased in the 100 ppm MeIQx group as compared to the
      control value. No histopathological changes indicating obvious toxicity of MeIQx
      were observed in the major organs other than the liver and large intestine. In
      conclusion, our results clearly indicate that MeIQx selectively targets the liver
      and large intestine of rats as organs for the toxicity, but dose not affect the
      other major organs at low doses.

PMID- 9641822
TI  - [13-week subchronic oral toxicity study of phaffia colour in F344 rats].
AB  - A 13-week subchronic oral toxicity study of phaffia colour was performed in both
      sexes of F344 rats by feeding of CRF-1 powder diet containing 0, 0.2, 0.6, 1.7
      and 5%. Rats were randomly divided into 5 groups, each consisting of 10 males and
      10 females. No animals died during the administration period. There were no
      treatment-related changes in body weight gain, hematological and blood
      biochemical examination. No treatment-related histopathological changes were also
      observed in any dosed groups. These findings indicate that the treatment of 5%
      phaffia colour in diet for 13 weeks does not cause any toxicological changes in
      rats.

PMID- 9641824
TI  - [Effects of dietary magnesium deficiency in the rat: with special reference to
      ultrastructural examination].
AB  - Epidemiologically, it has been suggested that dietary magnesium/calcium imbalance
      is associated with the risk of heart diseases. In the present study, the effects
      of magnesium deficiency and/or calcium over intake were investigated in rats.
      Male Sprague-Dawley rats were divided into 4 groups, and respectively fed basal
      diet (AIN-76) alone (Group 1), calcium-doubled AIN-76 diet (Group 2), magnesium
      deficient AIN -76 diet (Group 3) and magnesium-deficient/calcium-doubled AIN-76
      diet (Group 4) for 19 days. A biochemical assay using inductively coupled plasma
      showed that the magnesium concentrations of the femoral bone and serum were
      significantly (p < 0.001) lower in Groups 3 and 4 than in Group 1. The lipid
      peroxides of the heart in Group 4 and of the liver in Groups 3 and 4 were
      increased as compared to the Group 1 values although there was no statistical
      significance. Ultrastructurally, degenerative changes of organellas including
      mitochondria were observed in myocardial, liver and renal tubule cells of Groups
      2-4. Severe degeneration such as disorganization, lysis and disarrangement of
      myofibrils was most evident in myocardial cells of Group 4. Our results thus
      suggest that dietary magnesium deficiency gives rise to retrogressive changes in
      some organs including the heart, and concurrent calcium overintake
      synergistically enhances the myocardial injury due to magnesium deficiency.

PMID- 9641825
TI  - [A 13-week subacute oral toxicity study of pectin digests in rats].
AB  - A 13-week subacute oral toxicity study of pectin digests was performed in both
      sexes of F344 rats. Water containing 0, 0.15, 0.5, 1.5 or 5% pectin digests was
      fed to 10 males and 10 females per group to detect its toxicity. No animals died
      during the administration period. Body weight gain was suppressed in male of the
      5% group compared with the 0% group. Serum biochemistry analysis revealed a
      significant increase in BUN in male group treated with 5% and increases in CRN in
      male group treated with 1.5% or more. The weight of liver was significantly
      increased in female groups treated with 1.5% or more. Histopathologically, no
      treatment-related damage was observed in any dosed groups. Based on these
      results, the NOEL of pectin digests for both sexes in F344 rats was considered to
      be 0.5% in drinking water (male 545, female 657 mg/kg/day).

PMID- 9641826
TI  - [Stereochemical structure of d-borneol in "the Japanese Standards of Food
      Additives"].
AB  - d-Borneol is shown at "The Japanese Standards of Food Additives" the sixth
      edition. Though the absolute stereochemistry of this compound is described as 1S,
      2R-form, the opposite optical rotation for the same structure is described in
      other literatures. The application of improved Mosher's method to d-borneol
      resulted in 1R, 2S-form for its absolute stereochemistry.

PMID- 9641827
TI  - [Cytotoxicity of chemicals used in household products: estimation of eye
      irritating potency of 25 chemicals tested during 1991-1996].
AB  - Cytotoxicity potential of chemicals was evaluated by determining the
      concentrations inducing 50% reduction of neutral red (NR) uptake into Chinese
      hamster fibroblast V79 cells compared with control culture (IC50). The results of
      cytotoxicity test for surfactants with the data produced by the in vivo Draize
      eye and skin irritation test were compared. There was a good correlation between
      cytotoxicity and eye irritation score obtained from the Draize test. In contrast,
      no correlation was observed between Draize skin irritation score and cytotoxic
      potential of chemicals. Therefore, the NR cytotoxicity test was regarded as a
      possible in vitro model for predicting eye irritation. Based on the IC50 values
      in the NR cytotoxicity test, the eye irritation classification (weak, moderate
      and strong) for each chemical used in household products has been established. We
      evaluated the cytotoxicity of 25 chemicals used for antimicrobial, rubber
      accelerator, rubber antioxidant, ultraviolet absorber etc. in household products,
      and estimated the eye irritating potency of these test chemicals according to the
      criterion.

PMID- 9641828
TI  - [Specific determination of deltamethrin and tralomethrin by preparative HPLC and
      GC-ECD].
AB  - Tralomethrin quickly changes to deltamethrin in gas chromatograph by
      debromination. Therefore deltamethrin and tralomethrin are not able to be
      distinguished by gas chromatographic determination. A method for specific
      determination of deltamethrin and tralomethrin was established. The method
      consists of fractionation by high performance liquid chromatography and
      determination by gas chromatography. Recoveries of deltamethrin and tralomethrin
      spiked to three agricultural products were from 42 to 78% and from 18 to 76%,
      respectively with relative standard deviations ranging from 0.3 to 15%. From the
      analysis of samples spiked with tralomethrin, it was found that a part of
      tralomethrin quickly changed to deltamethrin in homogenate of agricultural
      products. The addition of phosphoric acid to the homogenate did not prevent the
      change of tralomethrin.

PMID- 9641829
TI  - [Analysis of B-3 desamido insulin in human insulin preparations by HPLC].
AB  - The content of A-21 desamido insulin (A-21 DI) and B-3 desamido insulin (B-3 DI)
      in human insulin preparations was measured by new RP-HPLC method using a neutral
      eluent (pH 6.5). Sometimes the content of B-3 DI in human insulin preparations
      was about two times larger than that of A-21 DI. In particular, in the case of
      neutral insulin injection, the content of B-3 DI has increased remarkably as the
      increase of total desamido content. The content of B-3 DI obtained by the new RP
      HPLC method will open the new aspect of the impurity test for insulin
      preparations.

PMID- 9641830
TI  - [Application of thermogravimetry to loss on drying test and water-content
      determination of drugs].
AB  - Thermogravimetry, one of the techniques of thermal analysis, was applied to the
      quality control of drug raw materials as a "Loss on Drying" or for "Water Content
      Determination". Twenty two kinds of drugs were selected for the comparison of the
      applicability of thermogravimetry with that of Loss on Drying Test and/or Water
      Content Determination by the Karl-Fisher method. In all kinds of drugs, it was
      ascertained that the results with thermogravimetry agreed well with those
      obtained by Loss on Drying test and/or Karl-Fisher method. In conclusion,
      thermogravimetry can be used as a substitute for the Loss on Drying test in cases
      where drug possess a water bound strongly. Further, thermogravimetry can be
      utilized for some drugs to which the Karl-Fisher method cannot be applied due to
      their insolubility in Karl-Fisher reagents.

PMID- 9641831
TI  - [Studies on the bottles of mineral water and the foreign plastic like
      substances].
AB  - The containers of mineral water and the foreign plastic substances which were
      found in the mineral water were investigated. Most of plastic bottles were made
      of polyethylene terephthalate (PET) and the caps were made of polypropylene (PP),
      polyethylene (PE) or aluminum. PE liners were attached to some caps. Most of the
      foreign plastic substances were PET while others were PE, PP, Teflon and rubber.
      Some bottles had a scratch on the top inside. The origin of most PET fragments
      was presumed to be scraped off the bottles by the lowering of the injection
      nozzle during the water filling process. The sources of the other substances were
      also determined.

PMID- 9641832
TI  - [Preliminary screening for antiviral AIDS drugs. VIII. Report for fiscal year
      1995].
AB  - Preliminary screening of antiviral AIDS drugs has been carried out using three
      different in vitro assay systems. Among 96 samples of different origin tested,
      two were shown to inhibit the growth of HIV in vitro. One of the positive samples
      (plant origin) has hopeful signs, as the ranges of effective doses are wider than
      those of most of positive samples which had been found by us.

PMID- 9641833
TI  - [Development of a geographical information system and its application to
      Escherichia coli O-157 patient distribution].
AB  - The so called Geographical Information System (GIS) is one of the basic tools for
      wide range of public health applications. We had developed a general purpose GIS
      and applied it to represent geographical distribution of patients of the
      bacterium E. coli O-157 which bursted out in Japan last early summer particularly
      at Sakai City in Osaka Prefecture. The patient record have been supplied from the
      Food Safety Office of the Ministry of Health and Welfare. These records were
      handled by EXCEL. The basic geographical data was constructed from the map data
      provided by Japan Geographical Survey Institute, and ArcView 2 was used as the
      map system. The maps were converted to Graphics Interchange Format (GIF) files
      and put on our Web server.

PMID- 9641834
TI  - [Dissemination of the Japanese version of the International Chemical Safety Card
      (ICSC) on the World Wide Web (WWW)].
AB  - ge of the Japanese version of the International Chemical Safety Cards (ICSC). We
      prepared the Japanese text files of ICSC, converted them into HTML files and also
      prepared the dictionary database for the retrieval system, using programs which
      we developed. These programs shortened the time of work remarkably. 2D- and 3D
      structures of chemicals were also incorporated in each ICSC page. Approximately
      900 ICSCs in Japanese are provided at the moment on the homepage.

PMID- 9641835
TI  - [First drafts of the Environmental Health Criteria (EHC) circulated for comments
      by IPCS in 1996.4-1997.3].

PMID- 9641836
TI  - [Estimated production by the official inspection of coal-tar dyes (including dye
      aluminum lakes) in 1996].
AB  - The number of official inspection of coal-tar dyes and their lakes from April in
      1996 till March in 1997 were 581 in total. The quantity which passed inspection
      amounted to 164.5 ton in Japan. The production of color in each month was
      summarised in Table1, and by each producing company in Table2. The food coal-tar
      dye produced in the largest quantity was Food Yellow No. 4, occupying 43.4% in
      this period.

PMID- 9641837
TI  - [Determination and survey of starting materials, intermediates, and subsidiary
      colors in food color of azo dye by high performance liquid chromatography].
AB  - A method for determination of starting materials, intermediates and subsidiary
      colors in food color of azo dye was developed by use of HPLC. The following
      conditions were used for analysis: column, L-column ODS (4.6 mm phi x 250 mmL);
      mobile phase, 0.02 M ammonium acetate (A), acetonitrile (B); concentration
      gradient, perform the linear concentration gradient from A:B (100:0) to (60:40)
      for 40 min; detection, starting materials and intermediates at 239 nm, and
      subsidiary colors at 510 nm. Standard material, domestic product and imported
      product were analyzed by the present HPLC method and impurities were measured.
      Recoveries of each impurity from azo dye averaged 99.1-103.5%. The detection
      limit was 0.05 microgram/g for each impurity.

PMID- 9641838
TI  - [Epinephrine Bitartrate Reference Standard (Control 951) of National Institute of
      Health Sciences].
AB  - The raw material for epinephrine bitartrate was tested for preparation of the
      "Epinephrine Bitartrate Reference Standard (Control 951)" of National Institute
      of Health Sciences. Analytical data obtained were as follows: melting point,
      148.6 degrees C (decomposition); UV spectrum, lambda max = 279 nm; IR spectrum,
      the same as that of JP Epinephrine Bitartrate Reference Standard (Control 792);
      optical rotation, [alpha]20D = -52.8 degrees; thin-layer chromatography, one
      impurity was detected; high-performance liquid chromatography, no impurity was
      detected; loss on drying, 0.01%; assay, 99.6% by potentiometric titration, 100.3%
      by spectrophotometry. Based on the above results, the raw material was authorized
      as the Epinephrine Bitartrate Reference Standard (Control 951) of National
      Institute of Health Sciences (Japanese Pharmacopoeia).

PMID- 9641839
TI  - [Riboflavin Reference Standard (Control 951) of National Institute of Health
      Sciences].
AB  - The raw material for riboflavin was tested for preparation of the "Riboflavin
      Reference Standard (Control 951)" of National Institute of Health Sciences.
      Analytical data obtained were as follows: melting point, 284.6 degrees C
      (decomposition): specific absorbance, E1cm1% = 857 (267 nm), 277 (373 nm), 326
      (445 nm); IR spectrum, the same as that of JP Riboflavin Reference Standard
      (Control 921); optical rotation, [alpha]20D = -135.6 degrees; thin-layer
      chromatography, three impurities were detected; high-performance liquid
      chromatography, a small amount of 10 impurities were detected: loss on drying,
      0.10%; assay, 100.4% by spectrophotometry. Based on the above results, the raw
      material was authorized as the Riboflavin Reference Standard (Control 951) of
      National Institute of Health Sciences (Japanese Pharmacopoeia).

PMID- 9641840
TI  - [Estradiol Reference Standard (Control 961) of National Institute of Health
      Sciences].
AB  - The raw material for estradiol was examined for preparation of the "Estradiol
      Reference Standard (Control 961)" of National Institute of Health Sciences.
      Analytical data obtained were as follows: melting point, 179.1 degrees C; UV
      spectrum, lambda max = 281 nm; IR spectrum, the same as that of the Estradiol
      Reference Standard of National Institute of Health Sciences (Control 931);
      optical rotation, [alpha]20D = +79.5 degrees; thin-layer chromatography, one
      impurity was detected; high-performance liquid chromatography (HPLC), a trace
      amount of three impurities were detected; loss on drying, 3.17%; assay, 99.4% by
      UV spectrophotometry and 99.0% by HPLC. Based on the above results, the raw
      material was authorized as the Estradiol Reference Standard (Control 961) of
      National Institute of Health Sciences.

PMID- 9641841
TI  - [dl-Camphor Reference Standard (Control 961) of National Institute of Health
      Sciences].
AB  - The raw material of dl-camphor was examined for the preparation of the "dl
      Camphor Reference Standard (Control 961)" of National Institute of Health
      Sciences. Analytical data obtained are as follows: UV spectrum, lambda max = 290
      nm; IR spectrum, the same as that of the present JP Camphor Reference Standard
      (Control 953); melting point, 179.1 degrees C; purity test by gas-chromatography
      (GC), three kinds of impurities were detected; assay by GC, 99.8%. Based on the
      above results, the candidate raw material was authorized as the dl-Camphor
      Reference standard (Control 961) National Institute of Health Sciences (Japanese
      Pharmacopoeia).

PMID- 9641842
TI  - [Chlormadinone Acetate Reference Standard (Control 961) of National Institute of
      Health Sciences].
AB  - The raw material for chlormadinone acetate was tested for preparation of the
      "Chlormadinone Acetate Reference Standard (Control 961)" of National Institute of
      Health Sciences. Analytical data obtained were as follows: melting point, 215. 3
      degrees C; UV spectrum, lambda max = 283.5 nm; IR spectrum, the same as that of
      JP Chlormadinone Acetate Reference Standard (Control 885); optical rotation,
      [alpha]20D = -13.0 degrees; thin-layer chromatography, one impurity was detected;
      high-performance liquid chromatography, two impurities were detected; loss on
      drying, 0.01%; assay, 99.4% by spectrophotometry and 99.5% by HPLC. Based on the
      above results, the raw material was authorized as the Chlormadinone Acetate
      Reference Standard (Control 961) of National Institute of Health Sciences
      (Japanese Pharmacopoeia).

PMID- 9641843
TI  - [Hydrocortisone Acetate Reference Standard (Control 961) of National Institute of
      Health Sciences].
AB  - The raw material of hydrocortisone acetate was tested for the preparation of the
      "Hydrocortisone Acetate Reference Standard (Control 961)". Analytical data
      obtained were as follows: IR spectrum, specific absorption wave numbers at 3428,
      1748, 1723, 1631, and 1375 cm-1; specific absorbance, E1cm1% (242 nm) = 406; thin
      layer chromatography, no impurities were detected until 0.05 microgram; high
      performance liquid chromatography (HPLC), 2-3 impurities were detected and the
      amount of the total impurities was estimated to be about 0.2%; assay by HPLC,
      100.7%. Based on the above results, the raw material was authorized as the
      Japanese Pharmacopoeia Reference Standard (Control 961).

PMID- 9641844
TI  - [Ulinastatin Reference Standard (Control 971) of the National Institute of Health
      Sciences].
AB  - The "Ulinastatin Reference Standard (control 971)" of National Institute of
      Health Sciences was prepared. The standard material was evaluated in
      collaboration with one domestic laboratory, and the potency of trypsin inhibiting
      activity was determined to be 3, 100 units/vial by relative assay method against
      the Ulinastatin Reference Standard (control 942). Other analytical data obtained
      were as follows: UV maximum absorption was observed at 277 nm, and the molecular
      weight was estimated to be about 66,300 by gel filtration method. Maximum
      variance of material contents in 10 vials was 2.29%. Based on the above results,
      this standard material was authorized to be the "Ulinastatin Reference Standard
      (control 971)" of the National Institute of Health Sciences.

PMID- 9641845
TI  - [The Endotoxin Reference Standard of the National Institute of Health Sciences
      (the Japanese Pharmacopoeia Endotoxin Reference Standard) (Control 971)].
AB  - The third lot (Control 971) of the Endotoxin Reference Standard of the National
      Institute of Health Sciences (the Japanese Pharmacopoeia Endotoxin Reference
      Standard) was prepared. The potency of the new lot was assayed against USP
      Endotoxin Reference Standard (EC-6) and defined as containing 13,000 endotoxin
      units (EU) per vial by a collaborative study of 7 laboratories.

PMID- 9641846
TI  - [Exceptional Application of Content Uniformity Test and Weight Variation Test in
      the Japanese Pharmacopoeia 13 revision and usage of these tests for in-process
      tests].
AB  - The criteria of Content Uniformity test and Weight Variation test in JP 13 were
      greatly changed to reduce consumer's risk. The new criteria were set to keep the
      rate of defectives in lots passing the tests less than the acceptable rate.
      However, in some cases, the new criteria can not directly be applied to some
      formulations and several modifications are needed in the criteria. In this
      report, the several resolution of this problem are represented. The applicability
      of these tests for in-process tests is also discussed.

PMID- 9641847
TI  - [A method for knowing the statistical reliability of instrumental measurements].
AB  - The precision of instrumental measurements, usually expressed by SD (standard
      deviation) or RSD (relative standard deviation) is of importance in a society as
      well as in a world of analytical chemistry. For example, the detection limit and
      confidence intervals of calibration lines which are based on the precision are
      inevitable for regulatory science. As is well-known in statistics, however, a
      small number of repetitive experiments (e.g., 5) lead to a poor reliability of
      the precision. This presentation shows a method (called FUMI theory) which can
      provide a precision from a single measurement of noise and signal without any
      repetitive measurements. The statistical reliability of the precision from the
      FUMI theory corresponds to that from the repetitive method of 50 experiments.

PMID- 9641848
TI  - [Relationship between design of calibration and precision of measurement].
AB  - The method to estimate the confidence interval of calibration line was
      established. The method used the variance of measurement that can be predicted
      based on the background fluctuation. The validity of the estimated confidence
      interval was verified experimentally. The relationship between the calibration
      design and the analytical precision can be predicted with this method. The ill
      designed calibration line deteriorates the trueness of the measurement as well as
      the precision.

PMID- 9641849
TI  - [A proposal by the Japanese Pharmacopoeia for a method to set an endotoxin limit
      for parenteral drugs to be tested].
AB  - The Bacterial Endotoxins Test has been extensively revised in the JP 13. In
      addition to the limit test with gelation, adopted in the JP 12, quantitative
      methods using gel-clot, turbidimetric and chromogenic techniques have been
      adopted in the JP 13. As for the endotoxin limit for monographs, it was specified
      for Water for Injection alone in the JP 12. Since the issue of the JP 13
      Supplement is under consideration, the possibility of replacing the Pyrogen Test
      (which is required for some main products in the current JP 13 monographs) with
      the Bacterial Endotoxins Test is now being discussed. For international
      harmonization of the Bacterial Endotoxins Test, it seems to be preferable to
      follow (if acceptable) the FDA method that was established in 1987 to set an
      endotoxin limit for products intended for parenteral use. This would then be
      followed by both the USP and EP. Thereby a draft for the Method to set the
      Endotoxin Limit, which is to be described in the Information chapter of the JP 13
      Supplement, is being prepared. This report details an explanation of the draft,
      the definition of the endotoxin unit (EU) and its defined process, and the
      compliance with the replacement of the Pyrogen Test by the Bacterial Endotoxins
      Test, etc.

PMID- 9641850
TI  - [Studies on the molecular weight standards for size-exclusion chromatography-
      standardization of a molecular weight standard for water-soluble polymers].
AB  - The possibility of the standardization of molecular weight standards for size
      exclusion chromatography (SEC) was investigated in the case of water-soluble
      polysaccharides such as dextran, hyaluronate and chitosan. In the case of
      dextran, comparing the method adopted for dextran in EP and BP, it was shown that
      pullulan, one of commercially available molecular weight standards, can be used
      in usual SEC method. For hyaluronate and chitosan, applying the Mark-Houwink
      correction to the calibration curve obtained by pullulan, the acceptable
      molecular weights could be estimated.

PMID- 9641851
TI  - Craniofacial electromyogram activation response: another indicator of anesthetic
      depth.
AB  - OBJECTIVE: After finding that craniofacial EMG preceding a stimulus was a poor
      predictor of movement response to that stimulus, we evaluated an alternative
      relation between EMG and movement: the difference in anesthetic depth between the
      endpoint of EMG responsiveness to a stimulus and endpoint of movement
      responsiveness to that stimulus. We expressed this relation as the increment of
      isoflurane between the two endpoints. METHODS: We measured EMG over the frontalis
      muscle, over the corrugator muscle, and between the Fp2 and the mastoid process
      as patients emerged from general anesthesia during suture closing of the surgical
      incision. Anesthesia was decreased by controlled washout of isoflurane while
      maintaining 70% N2O, and brain isoflurane concentrations ((C)isoBrain) were
      calculated. We studied a control group of 10 patients who received only surgical
      stimulation, and 30 experimental patients who intermittently received test
      stimuli in addition to the surgical stimulation. Patients were observed for
      movement responses and EMG records were evaluated for EMG activation responses.
      We defined an EMG activation response to be a rapid voltage increase of at least
      1.0 microV RMS above baseline, with a duration of at least 30 s, in at least one
      of the three EMG channels. Patient responses to stimuli were classified as either
      an EMG activation response without a move response (EMG+), a move response
      without an EMG activation response (MV+), both an EMG activation response and a
      move response (EMG+MV+), or no response. We defined the EMG+ endpoint to be the
      threshold between EMG+ response and nonresponse to a stimulus, and estimated
      (C)isoBrain at this endpoint. We similarly defined the move endpoint and
      estimated the move endpoint (C)isoBrain. We then calculated the increment of
      (C)isoBrain at the EMG+ endpoint relative to the move endpoint. MAIN RESULTS: For
      the 30 experimental patients, the initial response to a test stimulus was an EMG+
      in 14 patients (47%), an EMG+MV+ in 12 patients (40%), and a MV+ in 1 patient
      (3%); no response occurred by the time surgery was completed in 3 patients (10%).
      No response occurred in 7 of the control patients (70%). Of the 14 patients with
      an initial EMG+ response to a test stimulus, 9 patients later had a move
      response. For these 9 patients, the increment of (C)isoBrain between the EMG+
      endpoint and move endpoint was 0.11 +/- 0.04 vol%, (mean +/- SD). CONCLUSIONS:
      Our results suggest that, given the circumstances of our study, an EMG activation
      response by a nonmoving patient indicates that the patient is at an anesthetic
      level close to that at which movement could occur. However, because the first EMG
      activation response may occur simultaneously with movement, the EMG activation
      response cannot be relied upon to always herald a move response before it occurs.
      Our results also suggest that EMG responsiveness to a test stimulus may be used
      to estimate the anesthetic depth of an individual patient.

PMID- 9641853
TI  - Clinical evaluation of tracheal pressure estimation from the endotracheal tube
      cuff pressure.
AB  - OBJECTIVE: Air flow through an endotracheal tube causes a pressure drop across
      the tube. This pressure drop creates a difference between air pressure measured
      in the trachea and the pressure measured in the breathing circuit, which can lead
      to errors when calculating pulmonary mechanics and when setting ventilators. We
      have developed a method of estimating tracheal pressure from the pressure in the
      endotracheal tube cuff and tested this system in clinical trials. METHODS:
      Pressure measurement ports were placed between the Y piece of the ventilator
      circuit and the ETT connector, in the trachea at the carinal end of the ETT, and
      in the ETT cuff inflation line. Tracheal pressures and cuff pressures were found
      at end-inspiration and end-expiration (no flow states) and used to define a
      linear relationship between cuff pressure and tracheal pressure. Using the
      estimated tracheal pressure (Ptrach) and the measured pressure at the Y piece of
      the breathing circuit (PY), the pressure drop across the ETT was found as a
      function of flow through the tube. Tracheal pressure was then calculated from the
      flow-dependent pressure drop and PY. Tests of this system were performed in six
      patients in the operating room and six patients in the intensive care unit.
      RESULTS: The flow-based tracheal pressure estimates were within 0.7 +/- 0.4 cm
      H2O of actual tracheal pressure (mean +/- SD). At peak inspiratory pressure the
      difference averaged 0.5 +/- 0.3 cm H2O. The difference between our estimate of
      tracheal pressure and actual tracheal pressure was always less than 1 cm H2O.
      CONCLUSION: The flow-based tracheal pressure estimates were accurate during
      intermittent spontaneous breathing, but not during spontaneous breathing or with
      a poorly inflated cuff. The estimates were more immune to noise than the cuff
      based estimates of tracheal pressure. The estimates of tracheal pressure measured
      from the ETT cuff should be accurate enough for clinical use in the operating
      room.

PMID- 9641852
TI  - New equipment for neuromuscular transmission monitoring: a comparison of the TOF
      Guard with the Myograph 2000.
AB  - OBJECTIVE: The present study is to clarify whether the bias and limits of
      agreement of the TOF-Guard and the mechanomyograph differ from those of two
      mechanomyographs on contra lateral arms. Previous studies of the bias and limits
      of agreement between acceleromyographical (TOF-Guard) and mechanomyographical
      measurements of neuromuscular transmission did not take the error introduced by
      using contra lateral arms into consideration. METHODS: Fifty-two women undergoing
      gynecological surgery were anesthetized with midazolam, fentanyl, thiopental,
      halothane and nitrous oxide. Neuromuscular blockade was induced and maintained
      with atracurium. In 32 patients, neuromuscular monitoring was performed with a
      Myograph 2000 on one hand and a TOF-Guard at the other (M/T group). In 20
      patients, monitoring was performed with a Myograph 2000 at both hands (M/M
      group). Train-of-four stimulations were applied to the ulnar nerve at the wrist
      in both groups. Bias and limits of agreement between the contra lateral hands in
      each group were calculated as proposed by Bland and Altman. RESULTS: When the TOF
      ratio was 0.25, TOF ratio bias and limits of agreement in the M/T group were 0.86
      and 17.58 to -15.85, respectively. Corresponding values in the M/M group were 
      1.75 and 12.3 to -8.8. Bias in the M/T group decreased significantly to -8.1 when
      TOF ratio increased to 0.70, resulting in limits of agreement of 12.1 to -28.4.
      The corresponding values in the M/M group were bias 2.0 and limits of agreement
      10.7 to -6.7. TOF-Guard bias for onset time and time to 5% recovery of T1 (first
      twitch in TOF) were -19s and -1.5 min, respectively; both values differed
      significantly from zero (P < 0.05). Taken together with the changing TOF-ratio
      bias during recovery in the M/T group, these results indicate different onset and
      recovery curves for the two monitoring devices. CONCLUSIONS: Due to wide limits
      of agreement and different recovery courses, acccleromyographic and
      mechanomyographic recordings of neuromuscular transmission cannot be used
      interchangeably. The substantial variation between simultaneous
      mechanomyographical recordings of neuromuscular transmission obtained in contra
      lateral arms suggests that this factor should be taken into account when studying
      new neuromuscular monitoring techniques using the two-arm technique.

PMID- 9641854
TI  - Transcranial Doppler blood flow velocity versus 133Xe clearance cerebral blood
      flow during mild hypothermic cardiopulmonary bypass.
AB  - OBJECTIVE: Transcranial doppler (TCD) is used during cardiopulmonary bypass (CPB)
      to assess cerebral emboli and to estimate cerebral perfusion. We sought to
      compare TCD middle cerebral artery blood flow velocity (Vmca) to 133Xe clearance
      cerebral blood flow (CBF) measurements during mild hypothermic CPB thus
      determining its utility in cerebral perfusion assessment. METHODS: Thirty-four
      patients undergoing mild hypothermic CPB (35 degrees C) were studied and had
      comparisons of Vmca and 133Xe CBF at three time intervals, 10, 30 and 60 min
      after the institution of CPB. Linear regression analysis was performed on data
      from each of the 3 intervals as well as for pooled data from all 3 periods.
      RESULTS: The correlation coefficients for the 3 time periods were, r = 0.32 (p =
      0.12), r = 0.32 (p = 0.11), r = 0.48 (p = (0.02), respectively. The pooled data
      correlation had a coefficient of 0.34 (p = 0.003). CONCLUSION: These findings
      suggest that TCD Vmca is a relatively poor correlate of CBF during mild
      hypothermic CPB.

PMID- 9641855
TI  - The application of a modified proportional-derivative control algorithm to
      arterial pressure alarms in anesthesiology.
AB  - OBJECTIVE: We have developed an arterial pressure alarm system based on a
      modified proportional-derivative (PD) controller algorithm, and prospectively
      tested its ability to predict significant hypotensive episodes, defined as
      systolic arterial pressure < 80 mmHg, in comparison to conventional limit alarms.
      METHODS: The alarm algorithm was tuned to detect hypotension using selected
      invasive arterial pressure traces taken from ten patients who had large intra
      operative arterial pressure changes. The algorithm's performance was then tested
      prospectively in comparison to conventional limit alarms and median filtered
      limit alarms, set at 85 mmHg and 90 mmHg, for its ability to predict hypotensive
      episodes in a further 100 patients who required invasive arterial pressure
      monitoring. RESULTS: For the PD alarm algorithm, onset times for significant
      hypotensive episodes were between those of limit alarms set at 85 mmHg and 90
      mmHg. Offset times were similar to the 85 mmHg limit alarms. The false positive
      rate was 34% compared with 45-64% for the other alarms (p < 0.01). Using our
      definitions, there was one false negative in the PD group, being a 15 second drop
      in observed arterial pressure, when a non invasive blood pressure cuff was
      inflated above the arterial line. CONCLUSIONS: An arterial pressure alarm system
      design based on a closed loop control algorithm offered improved perform ance
      over conventional limit alarms and in addition provided a graded output of
      severity of the hypotension.

PMID- 9641856
TI  - Pulse oximetry monitoring and late postoperative hypoxemia on the general care
      floor.
AB  - Hypoxemia has long been recognized as a risk to patients in the operating room
      and postanesthesia care unit, and hemoglobin oxygen saturation (HbO2) monitoring
      with pulse oximetry has become a standard of care in these areas. There is
      growing evidence, however, suggesting that later postoperative hypoxemia also may
      play a role in organ dysfunction leading to morbidity and mortality. Economic
      pressures to move patients earlier from expensive postanesthesia recovery and
      intensive care areas to the general care floor -- where nurse-to-patient ratios
      are lower and lines of sight and sound may be impaired by walls and curtains --
      may lead to inadequate surveillance of at-risk patients. These patient-management
      trends underscore the importance of improved monitoring of respiratory status on
      the general care floor. In this environment, telemetric pulse oximetry monitoring
      may represent a cost-effective approach to maximizing quality of care while
      enhancing risk management. This review discusses late postoperative hypoxemia and
      identifies areas for further investigation.

PMID- 9641857
TI  - Modeling in anesthesia.
AB  - A model can be defined as an abstraction of reality which accounts for those
      properties ofa phenomenon that are pertinent to the purpose of the model. Models
      are used in anesthesia to understand the various physiologic, pharmacological and
      physical processes that occur during anesthesia. Indeed, many different types of
      models that comply with our definition can be distinguished. Early models
      consisted of electrical models of the arterial blood dynamics and cardiovascular
      system. Physical models of drug uptake and distribution have been developed to
      explain the kinetics of volatile anesthetics in the body. The goal of this paper
      is to introduce the reader to some of the types of models that been used to
      facilitate education and research in anesthesia. These examples will elucidate
      the steps involved in developing a model and the various types of models that
      have proven useful.

PMID- 9641858
TI  - Anesthetic safety always an issue with obstructive sleep apnea.

PMID- 9641859
TI  - Reporting of anesthesia-related incidents: the New Jersey experience.

PMID- 9641860
TI  - Debate on reuse of "disposable" medical equipment fueled by FDA.

PMID- 9641861
TI  - Continuous monitoring of intraocular pressure is helpful in testing hemodynamic
      response to anesthesia and to changes in body position.

PMID- 9641862
TI  - Expert weighs factors on reuse of disposables, urges safety criteria and new
      studies.

PMID- 9641882
TI  - Molecular pattern of ductal pancreatic cancer.
AB  - Our understanding of the molecular pathology underlying the development and
      progression of ductal pancreatic cancer has been revolutionised during the last 5
      years due to the spectacular development of novel molecular biological
      techniques. In the present article, we describe key molecular alterations of
      sporadic and inherited ductal pancreatic cancer. Overexpression of growth factors
      and growth factor receptors are present in a significant proportion of this
      tumour type. Mutation of the K-ras oncogene, and disruption of p53 or p16 tumour
      suppressor gene abrogates the control of the cyclin-dependent kinases (cdk) and
      retinoblastoma (Rb) gene pathway, causing continuous growth of the pancreatic
      tumour. Inactivation of the SMAD4 tumour suppressor gene leads to loss of the
      inhibitory influence of the transforming growth factor beta signalling pathway.
      Lost or decreased expression of retinoid receptors and failure of telomerase
      activity may play a role in pancreatic carcinogenesis. Tumour-associated
      proteinases, matrix metalloproteinases and plasminogen activators are reported to
      be involved in pancreatic cancer invasion and metastasis. Furthermore, the
      cytogenetic changes in this cancer are summarised. This molecular pattern
      distinguishes pancreatic cancer from other epithelial tumours and represents a
      promising basis for the development of diagnostic and other clinical
      applications.

PMID- 9641883
TI  - Pathology and biology of pancreatic ductal adenocarcinoma.
AB  - INTRODUCTION: Ductal adenocarcinoma of the pancreas is a highly aggressive tumor
      with early local spread beyond the pancreas, predominantly to the
      retroperitoneum, but also with invasion of adjacent great vessels and adjacent
      organs. DISCUSSION: Anterior extension may lead to perforation of the visceral
      peritoneum and spread within the peritoneal cavity. Cytology in peritoneal lavage
      can be positive before any peritoneal metastasis is seen. Invasion of lymphatics
      and veins as well as perineural invasion are common. The lymph drainage of the
      pancreas is multidirectional to superior, inferior, anterior, posterior and left
      lymph nodes. In node-negative cases, isolated tumor cells in the sinus of
      regional lymph nodes may be found by immunocytochemistry; such findings must be
      distinguished from micrometastasis. The same applies to isolated tumor cells in
      bone marrow. PROGNOSIS: The independent prognostic significance of isolated tumor
      cells in the regional lymph nodes and in the bone marrow remains to be proven.
      For classification of anatomic extent the new, fifth edition ( 1997) of the UICC
      TNM classification should be used. The complex Japanese classification cannot be
      directly compared with the UICC system. CONCLUSION: Tumor size and histologic
      grade influence the extent of spread. Anatomic extent and histologic grade are
      the strongest predictors of outcome.

PMID- 9641884
TI  - Resection of pancreatic cancer--surgical achievements.
AB  - INTRODUCTION: Looking back at the initially dismal record for pancreatic cancer
      surgery - Whipple himself felt that a 30-35% mortality was justifiable (!) -
      significant progress has been made. PROGRESS: The operative mortality has fallen
      below 5% and the serious complications of pancretic resections such as leaks and
      haemorrhage have been reduced to some 10% and we are better equipped to deal with
      these if they occur. The 5-year-survival of patients in whom pancreatic cancer
      was amenable to an R0-resection has risen to 30%. These are the surgical
      achievements using the standard Kausch-Whipple technique alone. There has been no
      improvement in these results, either by increasing radicality (regional
      pancreatectomy) or by reducing it (pylorus-preserving pancreatoduodenectomy). The
      same can be said of all other modalities of oncological treatment that have been
      tried so far: adjuvant radiochemotherapy, regional chemotherapy, hormonal or
      genetic manipulations. PERSPECTIVE: This does not mean that we should reduce
      efforts at improving early detection of the disease and unravelling its complex
      molecular biology. On the contrary, the results of surgery alone in spite of all
      improvements seem to have reached a plateau that gives little cause for
      complacency.

PMID- 9641885
TI  - Prognostic factors in ductal pancreatic cancer.
AB  - INTRODUCTION: The diagnosis of pancreatic adenocarcinoma remains a devastating
      life event for most patients and their families. Many patients with this
      relatively common malignancy present at a stage of disease not amenable to cancer
      directed resectional therapy, and are treated via nonoperative palliative
      measures, with median survival of 4-8 months post-diagnosis. CONCLUSION: A
      minority of patients present with disease limited to the pancreas and
      periampullary region and are candidates for resectional therapy. The prognosis
      for these patients is determined by several factors: clinicopathologic staging,
      tumor biology and molecular genetics, perioperative factors and the use of
      postoperative adjuvant therapy.

PMID- 9641886
TI  - Resection and radiochemotherapy of pancreatic cancer--the future?
AB  - BACKGROUND: To improve the surgical outcome after resection of pancreatic
      adenocarcinomas, multimodal treatment concepts need to be applied and improved.
      The controversies among those being pro and contra adjuvant treatment need an up
      to-date review of the indications and results achievable with various treatment
      modalities. PATIENTS/METHODS: The literature regarding the indications and
      results of adjuvant/neoadjuvant therapies in pancreatic cancer was reviewed to
      provide a solid base for current recommendations and future developments. The
      biology of the disease in the spontaneous course, after surgery and during/after
      various palliative and adjuvant/neoadjuvant treatment modalities was focussed on,
      to characterise the disease for an optimally targeted treatment in conjunction
      with surgical removal of the tumour. The results of systemic and regional
      chemotherapy and radiotherapy, either alone or in combination, before, during and
      after surgery were critically analysed with respect to the oncological
      possibilities and pitfalls of each treatment method. RESULTS: In two randomised
      trials, one testing postoperative radiochemotherapy (GITSG), and one
      postoperative chemotherapy, the adjuvant treatment achieved a significant
      prolongation of the median survival time. The 5-year and 10-year survival rates
      were improved in the GITSG study. The EORTC-GITCCG trial could not confirm the
      benefit of adjuvant radiochemotherapy. This study had a different design than the
      GITSG trial. Several historical control studies supported the beneficial effect
      of postoperative radiochemotherapy. In three historical control trials using
      regional chemotherapy, one with intraoperative radiotherapy, the survival times
      were improved compared with surgery alone. Intraoperative or postoperative
      radiotherapy as single modalities might reduce local relapses, but a survival
      advantage is still debated. Preoperative neoadjuvant radiochemotherapy has
      several advantages (downstaging, devitalising margins and lymph node metastases,
      compatibility of treatment vs. postoperative radiochemotherapy), and does not
      seem to increase the postoperative morbidity. Several trials have confirmed the
      feasibility of this concept, but no survival advantage has yet been proven.
      Systemic and regional chemotherapy is able to downstage primarily nonresectable
      pancreatic cancers. CONCLUSIONS: Postoperative adjuvant radiochemotherapy with up
      to-date protocols can be recommended for routine treatment, if the surgeon or the
      patient desires to improve the usually remote prognosis after surgery alone. For
      those being indecisive or against adjuvant therapy, the participation in trials,
      e.g. the ESPAC 1 and 2 studies, is strongly recommended. Regarding our own
      positive experience with adjuvant regional chemotherapy and in view of the
      postresectional progression pattern, we currently favour adjuvant
      radiochemotherapy, with the chemotherapy delivered regionally via the celiac
      axis. This concept will be tested against surgery alone in the ESPAC 2 trial.
      Neoadjuvant therapies have a great potential, but should be conducted within
      studies, such as pre-, intra-, or postoperative radiotherapy.

PMID- 9641887
TI  - Quality of life after treatment of pancreatic cancer.
AB  - In the past decade there has been increasing focus on assessment of the quality
      of life (QoL) of patients with cancer. QoL is now a mandatory endpoint in many
      cancer clinical trials, particularly in interventions with palliative intent
      alone. Although QoL is difficult to define, a variety of specially designed and
      validated questionnaires has been developed to measure QoL in the clinical
      setting. In pancreatic cancer, assessment (QoL) is of paramount importance;
      however, little research has been conducted and until recently no disease
      specific QoL questionnaire existed. In this review we consider the quality of
      life of patients with pancreatic cancer, with particular reference to the
      symptoms and psychosocial consequences of the disease. The literature is
      critically examined on the approaches to evaluation of QoL in previous pancreatic
      cancer clinical trials. We then describe the impact on QoL following both
      "curative" and palliative surgical interventions and medical treatment, including
      endoscopic palliation and chemotherapy for pancreatic cancer. In the European
      Organisation for Research and Treatment of Cancer (EORTC) the questionnaire
      specific for pancreatic cancer, the QLQ-PAN26, is discussed as a standardised and
      valid assessment of QoL in international clinical trials. Finally,
      recommendations are made for future QoL research in pancreatic cancer.

PMID- 9641888
TI  - Prognostic significance of molecular alterations in human pancreatic carcinoma-
      an immunohistological study.
AB  - BACKGROUND: During the last decade, many molecular alterations have been
      described for pancreatic carcinomas. However, the clinical and prognostic value
      of these alterations has been discussed and is controversial. METHODS: An
      immunohistochemical study was performed in 82 cases of adenocarcinoma of the
      pancreas. Using specific antibodies, expression of EGF, EGF-receptor, cERB-B2,
      p53, p21CIP1, cyclin-D1, BCL-2, CD95 and KI67 was evaluated. RESULTS:
      Overexpression of the different molecules was found in 44-69% of the pancreatic
      carcinomas. With regard to clinico-pathological features, p53 positivity was more
      frequently found in advanced and undifferentiated tumours (P<0.05), EGF
      overexpression was significantly more frequent in advanced tumours (P<0.05) and
      CD95 overexpression was observed to a greater extent in undifferentiated tumours
      (P<0.05). Besides cyclin-D1, none of the molecules tested was of prognostic
      significance. Patients whose tumours expressed cyclin-DI lived significantly
      shorter than patients with cyclin-D1-negative tumours. However, in subgroup
      analyses of patients with the same tumour stage or tumour grade, even cyclin-D1.
      expression had no prognostic significance. CONCLUSION: These results demonstrate
      that the prognostic significance of the molecules tested here is low.
      Nevertheless, with regard to tumorigenesis and tumour biology of pancreatic
      carcinoma, determination of molecular alterations could provide important
      information about pancreatic cancer.

PMID- 9641889
TI  - Talc pleurodesis in recurrent pleural effusions.
AB  - BACKGROUND AND AIMS: The treatment of recurrent malignant pleural effusions is
      known to be difficult and varies from observation in asymptomatic patients to
      pleurectomy with varying results. This prospective study presents the efficacy
      and the limits of iodized talc pleurodesis in patients with malignant and non
      malignant recurrent pleural effusions. METHODS: In a prospective trial talc
      pleurodesis was performed in 50 patients with recurrent pleural effusions
      (malignant effusions: n=36, non-malignant effusions: n=14). After insertion of a
      chest tube and complete re-expansion of the lung, 5 mg of talc and 3 mg of thymol
      iodine were installed with 0.5 ml of 1% xylocaine/kg body weight and 30 ml 0.9%
      saline solution. The chest tube was removed after an average time of 4 days and
      chest radiographs were performed 1 month after instillation to evaluate the
      efficacy of pleurodesis. RESULTS: Successful therapy was achieved in 31 of 33
      patients (94%) with malignant effusions within a follow-up period of 7 months.
      Three patients died within 1 month after therapy due to progressive malignant
      disease. The treatment was successful in all cases of non-malignant effusions and
      complications did not occur in either group. CONCLUSIONS: These results indicate
      that pleurodesis with iodized talcum slurry is a simple and inexpensive method
      with high efficacy in controlling malignant and non-malignant pleural effusions.

PMID- 9641890
TI  - Positron emission tomography with F-18-deoxyglucose in patients with
      differentiated thyroid carcinoma, elevated thyroglobulin levels, and negative
      iodine scans.
AB  - INTRODUCTION: In patients with differentiated thyroid carcinoma, elevated serum
      levels of thyroglobulin (hTg) may occur in spite of otherwise negative diagnostic
      procedures and in particular in spite of a negative iodine-131 scan. Positron
      emission tomography with F-18-deoxyglucose (FDG-PET) is a potentially useful
      method for the detection of metastatic lesions or the recurrence of thyroid
      cancer. We aimed to investigate whether FDG-PET is capable of detecting
      metastatic lesions or recurrence in patients with differentiated thyroid
      carcinoma, elevated serum levels of thyroglobulin, and otherwise negative
      diagnostic procedures, including the iodine-131 scan. METHODS: From a group of
      500 patients with differentiated thyroid carcinoma, a subgroup of 32 patients had
      elevated serum hTg-levels, negative iodine- 131 scans, negative cervical and
      abdominal ultrasound, and negative X-ray of the chest. In 12 of these patients
      (hTg 77.8+/-94.3 ng/ml, range 1.5-277 ng/ml, median 20 ng/ml), FDG-PET was
      performed. All but one FDG-PET study was performed in a state of hypothyroidism
      (TSH 75.8+/-32.2 microIU/ml, range 31-116 microIU/ml, median 74.6 microIU/ml).
      RESULTS: In 6 of the 12 patients investigated, the FDG-PET was positive. In three
      of the patients, the diagnosis was confirmed by computed tomography or magnetic
      resonance imaging. In patients with a positive FDG-PET finding, the hTg level was
      146.7+/-90.1 ng/ml (23-277 ng/ml, median 144.5 ng/ml). In contrast, in patients
      with a negative finding the hTg level was only 9.0+/-7.6 ng/ml (range 1.5-17
      ng/ml, median 8.1 ng/ml), P=0.01. CONCLUSION: These preliminary results show that
      in patients with differentiated thyroid carcinoma, elevated hTg levels, and
      otherwise negative "conventional" diagnostic procedures, FDG-PET is helpful in
      detecting metastatic lesions.

PMID- 9641891
TI  - The role of fine-needle aspiration cytology and frozen section histology in
      management of differentiated thyroid cancer: the UK experience.
AB  - OBJECTIVE: A review of the literature was undertaken to determine the use by UK
      surgeons of fine-needle aspiration cytology (FNAC) and frozen section histology
      in management of differentiated thyroid carcinoma. RESULTS: The extent of FNAC
      use was highly variable, but commoner amongst more specialised surgeons who
      performed more than 25 thyroid operations per year. Such surgeons generally
      perform ipsilateral total lobectomy and isthmectomy for solitary thyroid nodule
      and use FNAC to assist in planning surgical strategy for differentiated thyroid
      cancer mainly by determining the likely extent of contralateral lobe resection
      and nodal dissection required. The use of frozen section histology to aid this
      decision intra-operatively is largely unreported in the UK literature.

PMID- 9641892
TI  - Morbidity of prophylactic lymph node dissection in the central neck area in
      patients with papillary thyroid carcinoma.
AB  - The benefits of prophylactic central neck dissection (PCND) in patients with
      papillary thyroid carcinoma (PTC) have not been clearly demonstrated so far and
      should be weighed against the potential risks of the procedure. The aim of the
      study was to assess the recurrent laryngeal nerve and parathyroid risks of PCND
      after total thyroidectomy in patients with PTC and to compare the results with
      those obtained in patients who underwent total thyroidectomy only. METHODS: We
      selected 100 patients who underwent a total thyroidectomy: 50 for nontoxic benign
      multinodular goiter (Group 1) and 50 for PTC (Group 2). Patients with PTC had no
      evidence of macroscopic lymph node invasion during surgery and underwent, in
      addition to the total thyroidectomy, a PCND. All of the 100 patients were
      operated on by two experienced endocrine surgeons. All patients had pre- and
      postoperative investigations of vocal cord movements. Calcemia and phosphoremia
      were systematically evaluated preoperatively and on day 1 and day 2 after
      surgery. All patients presenting a postoperative calcemia below 1.90 mmol/l were
      considered to present an early postoperative hypoparathyroidism and received
      calcium-vitamin D therapy. The hypoparathyroidism was considered permanent when
      calcium-vitamin D therapy was still necessary 1 year after surgery. RESULTS: None
      of the patients presented permanent nerve palsy. There were three cases of
      transient nerve palsy (6%) in Group 1 and two (4%) in Group 2. In Group 1 there
      was no permanent hypoparathyroidism and four cases of transient
      hypoparathyroidism (8%). In Group 2, seven patients presented transient
      hypoparathyroidism (14%) and two patients (4%) remained with definitive
      hypoparathyroidism. CONCLUSION: After total thyroidectomy for PTC, PCND does not
      increase recurrent laryngeal nerve morbidity but it is responsible for a high
      rate of hypoparathyroidism, especially in the early postoperative course. Even
      taking into account the possible benefits, the results make it difficult to
      advocate PCND as a routine procedure in all patients presenting a PTC.

PMID- 9641893
TI  - Prophylactic thyroidectomy in MEN IIA: does the calcitonin level correlate with
      tumor spread?
AB  - BACKGROUND: The fate of patients with multiple endocrine neoplasia of type II A
      (MEN II A) is determined by medullary thyroid carcinoma, which occurs in all
      cases. This has led to the therapeutic concept of prophylactic thyroidectomy in
      affected family members with the goal of removing the thyroid before the
      manifestation of carcinoma. We investigated a prophylactically thyroidectomized
      MEN II A population to determine whether the highly specific and sensitive tumor
      marker calcitonin correlates with tumor spread. PATIENTS AND METHODS: Fifteen
      patients with MEN II A (aged 4-24 years) who had undergone prophylactic
      thyroidectomy since 1990 were included in the study. Baseline and pentagastrin
      stimulated calcitonin levels were preoperatively determined in all cases. The
      indication for surgery was established on the basis of pathologic calcitonin
      levels in the first seven patients and on the basis of detected RET proto
      oncogene mutation in the other eight patients. Bilateral central lymphadenectomy
      was performed in all patients in addition to thyroidectomy. RESULTS: Histology
      demonstrated C-cell hyperplasia in five patients (aged 4-13 years), unilateral
      medullary microcarcinoma in six (aged 9-17 years) and a bilateral medullary
      microcarcinoma in three cases (aged 17-24 years). One 9-year-old boy with
      bilateral microcarcinoma already had a lymph node metastasis. The mean baseline
      calcitonin level correlated with the histologic findings (r=0.71, P=0.003) but
      there was no correlation between pentagastrin-stimulated calcitonin levels and
      histology (r=0.21, P=0.47). CONCLUSION: In MEN II A patients undergoing
      prophylactic thyroidectomy, baseline but not stimulated calcitonin levels already
      correlate with the histologic tumor stage at the stage of clinically occult C
      cell hyperplasia or medullary microcarcinoma. However, biochemical screening
      cannot reliably discriminate the transition from C-cell hyperplasia to invasive
      microcarcinoma. Individuals with MEN IIA should therefore undergo early
      prophylactic thyroidectomy once the diagnosis is confirmed by molecular genetic
      testing.

PMID- 9641894
TI  - Reoperation for persistent or recurrent primary hyperparathyroidism.
AB  - AIM: To analyse the causes and outcome of reoperations for persistent or
      recurrent primary hyperparathyroidism (HPT). MATERIALS AND METHODS: We reviewed
      the medical records of 38 patients who underwent reoperation between December
      1965 and April 1997 for persistent or recurrent primary HPT. During this period
      of time, 1448 patients underwent operation for primary HPT, 294 for renal HPT and
      58 for questionable disease, i. e. a total of 1800. In the 1448 cases of HPT, 22
      patients were reoperated after a first cervicotomy in the institution, i. e. a
      first reoperation rate of 1.5%. Sixteen patients were referred after unsuccessful
      parathyroid surgery. Six patients were reoperated on twice and one patient seven
      times for a graft-dependent recurrence. RESULTS: Reasons for failed parathyroid
      operations included tumour tissue in ectopic location (75%) or tumour tissue that
      had not been seen in normal position (19%), parathyreomatosis (2%), parathyroid
      cancer (2%) and graft-dependent hypercalcaemia (2%). Of the ectopic glands, 45 %
      were intrathymic, 12.5% intrathyroidal, 7.5% retro-oesophageal, 7.5% in the
      carotid sheath, 5% interthyrotracheal, 5% in the mediastinum (extrathymic), 5% in
      the aorto-pulmonary window, 2.5% undescended, 2.5% overdescended and 2.5%
      intertracheooesophageal. Of the patients, 38% had uniglandular lesions, 60%
      multiglandular lesions, and 2% parathyroid cancer. The histologically confirmed
      cause of HPT was adenoma in 50% of cases, hyperplasia in 38% and "normal" but
      overweight glands in 9.5%. Of the 38 patients studied, 15 presented one or more
      supernumerary glands (fifth to eighth gland). Reoperation was performed through a
      cervical incision in 82% of cases and using a mediastinal approach in 18% (8
      median sternotomies, 1 thoracoscopy). The success rate of the reoperations was
      92%. A total of 8% of patients suffered permanent unilateral vocal cord
      paralysis; 5% are definitely hypocalcaemic. The sensitivities of preoperative
      localization studies ranged from 69% for sestamibi scan and 63% for selective
      venous catheterization to 16% for computed tomography. CONCLUSION: Repeated
      parathyroidectomy can be avoided in more than 98% of patients if an experienced
      surgeon performs bilateral cervical exploration during the initial parathyroid
      operation. For patients with persistent or recurrent primary HPT, preoperative
      localization studies and a focused surgical approach can result in a 92% success
      rate with a minimal complication rate.

PMID- 9641895
TI  - Long-term follow-up of node-positive papillary thyroid carcinomas.
AB  - INTRODUCTION: We retrospectively reviewed the data of patients with papillary
      thyroid cancer who were node positive and treated at our department between 1955
      and 1994. Of 362 cases of papillary cancer, 134 were identified with lymph-node
      metastases (37%). METHODS: Two types of dissection procedures were applied by a
      large community of surgeons. When only the cervical central lymph nodes were
      involved, the procedure of choice was thyroidectomy, with local lymph-node
      excision (LD); if the lateral nodes were also affected, modified radical neck
      dissection (MRND) was applied. RESULTS: Of 88 patients considered to have minimal
      involvement, 70 underwent procedures of a lesser magnitude than MRND. Most of the
      operations were localised "picking procedures". Recurrence of the disease
      developed in 16 cases, twice in 8 of these. The new tumourous lymph node was
      found to be ipsilateral in every case and close to the place of the first
      operation. The rate of recurrence was 23%. In the same group, 18 MRNDs were
      performed, with ipsilateral lymph-node recurrence in six cases. In 41 patients
      undergoing surgery for extended lymph-node metastases, conservative excisions
      were carried out in 17 and MRND in 24 cases, including six bilateral dissections.
      In this group, late recurrence was 47%. CONCLUSION: The results of the follow-up
      of 30 childhood and juvenile patients with papillary thyroid carcinoma is very
      interesting; all of our young patients are alive.

PMID- 9641896
TI  - Menin mutations in the diagnosis and prediction of multiple endocrine neoplasia
      type 1.
AB  - INTRODUCTION: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant
      disorder characterized by the development of multiple endocrine adenomas,
      typically in the pancreas, anterior pituitary, and parathyroid glands. The
      disease is associated with germ-line mutations of the menin gene, a putative
      tumor-suppressor gene located on human chromosome 11q13. METHODS: To facilitate
      the diagnosis and prediction of MEN1 in patients and their relatives, we
      developed a molecular two-step strategy to screen for menin gene mutations. DNA
      fragments covering the entire menin coding sequence are generated from patient
      cDNA by polymerase reaction (PCR) and subsequently analyzed by single-strand
      conformational polymorphism electrophoresis (SSCP). Fragments with aberrant SSCP
      migration are DNA-sequenced to directly characterize menin mutations. In a second
      diagnostic step, genomic DNA of healthy relatives of the corresponding MEN1 index
      patient is analyzed by PCR, with only the specific exon amplified harboring the
      family-specific mutation. Mutation-specific restriction enzyme digestion of this
      PCR product finally allows the identification of mutation carriers through
      pathological restriction fragment patterns. RESULTS: Using this approach, we
      identified an in-frame deletion mutation (delta Tyr Met) located in menin exon 4
      (codon 227-228) that co-segregates with the disease phenotype in a large MEN1
      family from Southern Germany. CONCLUSION: It is likely that the direct molecular
      analysis of menin gene mutations will replace the genetic and biochemical
      screening tests currently used in the clinical management of MEN1 families. In
      addition, these studies may provide clues to the tumor biology of both sporadic
      and MEN1-associated endocrine adenomas.

PMID- 9641897
TI  - Histological verification of positive fluorine-18 fluorodeoxyglucose findings in
      patients with differentiated thyroid cancer.
AB  - Fluorine-18 fluorodeoxyglucose and positron emission tomography (FDG-PET) is a
      new imaging modality used in the follow-up of patients with differentiated
      thyroid cancer if the results of (131)I scintigraphy are negative in spite of an
      elevated thyroglobulin level. The aim of this retrospective analysis was to
      estimate the value of FDG-PET regarding the operability of patients with positive
      findings. From January 1994 to October 1997, we investigated 60 patients with
      differentiated thyroid carcinoma by FDG-PET. Thirteen patients were operated on
      after positive findings. Most of these lesions were suspected of having lymph
      node involvement or local recurrences in the thyroid bed. One patient showed a
      solitary distant metastasis in the scapula. Thirteen of 16 operations in these 13
      patients confirmed the suspected involvement of thyroid cancer. The false
      positive findings were caused by inflamed lymph nodes in two cases and benign
      thymus tissue in one case. We conclude that PET is a useful diagnostic tool to
      guide early surgical therapy in patients with (131)I negative differentiated
      thyroid carcinoma.

PMID- 9641898
TI  - Ampullectomy for adenoma of the papilla and ampulla of Vater.
AB  - INTRODUCTION: The frequency of malignant adenomas of the papilla figures between
      15 and 30%. Villous adenoma is considered to be a premalignant lesion. TREATMENT:
      Resection of the papilla is indicated in large tubular and small tubulovillous
      adenoma. Ampullectomy, however, is mandatory in villous adenoma with severe
      dysplasia and large villous or tubulovillous adenoma. If villous adenoma with a
      low-risk pT1 N0 M0 G1/2-cancer is treated by ampullectomy, local lymph dissection
      should also be performed. Ampullectomy includes extirpation of the ampulla of
      Vater and reinsertion of the common bile duct and the pancreatic main duct into
      the duodenal wall. RESULTS: Hospital mortality after ampullectomy is less than
      0.4%, and surgical morbidity, e.g., cholangitis, below 10%.

PMID- 9641899
TI  - A vision of surgery: the concept OP 2000.

PMID- 9641906
TI  - Plasticity induced by shock waves in nonequilibrium molecular-dynamics
      simulations 
AB  - Nonequilibrium molecular-dynamics simulations of shock waves in three-dimensional
      10-million atom face-centered cubic crystals with cross-sectional dimensions of
      100 by 100 unit cells show that the system slips along all of the available 111
      slip planes, in different places along the nonplanar shock front. Comparison of
      these simulations with earlier ones on a smaller scale not only eliminates the
      possibility that the observed slippage is an artifact of transverse periodic
      boundary conditions, but also reveals the richness of the nanostructure left
      behind. By introducing a piston face that is no longer perfectly flat, mimicking
      a line or surface inhomogeneity in the unshocked material, it is shown that for
      weaker shock waves (below the perfect-crystal yield strength), stacking faults
      can be nucleated by preexisting extended defects.

PMID- 9641907
TI  - Design and fabrication of topologically complex, three-dimensional
      microstructures 
AB  - Two concepts for use in the fabrication of three-dimensional (3D) microstructures
      with complex topologies are described. Both routes begin with a two-dimensional
      (2D) pattern and transform it into a 3D microstructure. The concepts are
      illustrated by use of soft lithographic techniques to transfer 2D patterns to
      cylindrical (pseudo-3D) substrates. Subsequent steps-application of uniaxial
      strain, connection of patterns on intersecting surfaces-transform these patterns
      into free-standing, 3D, noncylindrically symmetrical microstructures.
      Microelectrodeposition provides an additive method that strengthens thin metal
      designs produced by patterning, welds nonconnected structures, and enables the
      high-strain deformations required in one method to be carried out successfully.

PMID- 9641908
TI  - From shifting silt to solid stone: the manufacture of synthetic basalt in ancient
      mesopotamia 
AB  - Slabs and fragments of gray-black vesicular "rock," superficially resembling
      natural basalt but distinctive in chemistry and mineralogy, were excavated at the
      second-millennium B.C. Mesopotamian city of Mashkan-shapir, about 80 kilometers
      south of Baghdad, Iraq. Most of this material appears to have been deliberately
      manufactured by the melting and slow cooling of local alluvial silts. The high
      temperatures (about 1200 degreesC) required and the large volume of material
      processed indicate an industry in which lithic materials were manufactured
      ("synthetic basalt") for grinding grain and construction.

PMID- 9641909
TI  - (Mg,Fe)SiO3-perovskite stability under lower mantle conditions 
AB  - In three different experiments up to 100 gigapascals and 3000 kelvin, (Mg,Fe)SiO3
      perovskite, the major component of the lower mantle, remained stable and did not
      decompose to its component oxides (Mg, Fe)O and SiO2. Perovskite was formed from
      these oxides when heated in a diamond anvil cell at pressures up to 100
      gigapascals. Both MgSiO3 crystals and glasses heated to 3000 kelvin at 75
      gigapascals also formed perovskite as a single phase, as evident from Raman
      spectra. Moreover, fluorescence measurements on chromium-doped samples
      synthesized at these conditions gave no indication of the presence of MgO.

PMID- 9641911
TI  - Gold nanoelectrodes of varied size: transition to molecule-like charging 
AB  - A transition from metal-like double-layer capacitive charging to redox-like
      charging was observed in electrochemical ensemble Coulomb staircase experiments
      on solutions of gold nanoparticles of varied core size. The monodisperse gold
      nanoparticles are stabilized by short-chain alkanethiolate monolayers and have 8
      to 38 kilodaltons core mass (1.1 to 1.9 nanometers in diameter). Larger cores
      display Coulomb staircase responses consistent with double-layer charging of
      metal-electrolyte interfaces, whereas smaller core nanoparticles exhibit redox
      chemical character, including a large central gap. The change in behavior is
      consistent with new near-infrared spectroscopic data showing an emerging gap
      between the highest occupied and lowest unoccupied orbitals of 0.4 to 0.9
      electron volt.

PMID- 9641910
TI  - Perennial Antarctic lake ice: an oasis for life in a polar desert.
AB  - The permanent ice covers of Antarctic lakes in the McMurdo Dry Valleys develop
      liquid water inclusions in response to solar heating of internal aeolian-derived
      sediments. The ice sediment particles serve as nutrient (inorganic and organic)
      enriched microzones for the establishment of a physiologically and ecologically
      complex microbial consortium capable of contemporaneous photosynthesis, nitrogen
      fixation, and decomposition. The consortium is capable of physically and
      chemically establishing and modifying a relatively nutrient- and organic matter
      enriched microbial "oasis" embedded in the lake ice cover.

PMID- 9641912
TI  - Giant electrostriction and relaxor ferroelectric behavior in electron-irradiated
      poly(vinylidene fluoride-trifluoroethylene) copolymer 
AB  - An exceptionally high electrostrictive response ( approximately 4 percent) was
      observed in electron-irradiated poly(vinylidene fluoride-trifluoroethylene)
      [P(VDF-TrFE)] copolymer. The material exhibits typical relaxor ferroelectric
      behavior, suggesting that the electron irradiation breaks up the coherent
      polarization domain (all-trans chains) in normal ferroelectric P(VDF-TrFE)
      copolymer into nanopolar regions (nanometer-size, all-trans chains interrupted by
      trans and gauche bonds) that transform the material into a relaxor ferroelectric.
      The expanding and contracting of these polar regions under external fields,
      coupled with a large difference in the lattice strain between the polar and
      nonpolar phases, generate an ultrahigh strain response.

PMID- 9641913
TI  - Neptune's eccentricity and the nature of the kuiper belt 
AB  - The small eccentricity of Neptune may be a direct consequence of apsidal wave
      interaction with the trans-Neptune population of debris called the Kuiper belt.
      The Kuiper belt is subject to resonant perturbations from Neptune, so that the
      transport of angular momentum by density waves can result in orbital evolution of
      Neptune as well as changes in the structure of the Kuiper belt. In particular,
      for a belt eroded out to the vicinity of Neptune's 2:1 resonance at about 48
      astronomical units, Neptune's eccentricity can damp to its current value over the
      age of the solar system if the belt contains slightly more than an earth mass of
      material out to about 75 astronomical units.

PMID- 9641914
TI  - Embryonic folate metabolism and mouse neural tube defects.
AB  - Folic acid prevents 70 percent of human neural tube defects (NTDs) but its mode
      of action is unclear. The deoxyuridine suppression test detects disturbance of
      folate metabolism in homozygous splotch (Pax3) mouse embryos that are developing
      NTDs in vitro. Excessive incorporation of [3H]thymidine in splotch embryos
      indicates a metabolic deficiency in the supply of folate for the biosynthesis of
      pyrimidine. Exogenous folic acid and thymidine both correct the biosynthetic
      defect and prevent some NTDs in splotch homozygotes, whereas methionine has an
      exacerbating effect. These data support a direct normalization of neurulation by
      folic acid in humans and suggest a metabolic basis for folate action.

PMID- 9641915
TI  - p115 RhoGEF, a GTPase activating protein for Galpha12 and Galpha13.
AB  - Members of the regulators of G protein signaling (RGS) family stimulate the
      intrinsic guanosine triphosphatase (GTPase) activity of the alpha subunits of
      certain heterotrimeric guanine nucleotide-binding proteins (G proteins). The
      guanine nucleotide exchange factor (GEF) for Rho, p115 RhoGEF, has an amino
      terminal region with similarity to RGS proteins. Recombinant p115 RhoGEF and a
      fusion protein containing the amino terminus of p115 had specific activity as
      GTPase activating proteins toward the alpha subunits of the G proteins G12 and
      G13, but not toward members of the Gs, Gi, or Gq subfamilies of Galpha proteins.
      This GEF may act as an intermediary in the regulation of Rho proteins by G13 and
      G12.

PMID- 9641916
TI  - Direct stimulation of the guanine nucleotide exchange activity of p115 RhoGEF by
      Galpha13.
AB  - Signaling pathways that link extracellular factors to activation of the monomeric
      guanosine triphosphatase (GTPase) Rho control cytoskeletal rearrangements and
      cell growth. Heterotrimeric guanine nucleotide-binding proteins (G proteins)
      participate in several of these pathways, although their mechanisms are unclear.
      The GTPase activities of two G protein alpha subunits, Galpha12 and Galpha13, are
      stimulated by the Rho guanine nucleotide exchange factor p115 RhoGEF. Activated
      Galpha13 bound tightly to p115 RhoGEF and stimulated its capacity to catalyze
      nucleotide exchange on Rho. In contrast, activated Galpha12 inhibited stimulation
      by Galpha13. Thus, p115 RhoGEF can directly link heterotrimeric G protein alpha
      subunits to regulation of Rho.

PMID- 9641917
TI  - Type IV pili, transient bacterial aggregates, and virulence of enteropathogenic
      Escherichia coli.
AB  - Type IV bundle-forming pili of enteropathogenic Escherichia coli are required for
      the localized adherence and autoaggregation phenotypes. Whether these pili are
      also required for virulence was tested in volunteers by inactivating bfpA or bfpT
      (perA) encoding, respectively, the pilus subunit and the bfp operon
      transcriptional activator. Both mutants caused significantly less diarrhea.
      Mutation of the bfpF nucleotide-binding domain caused increased piliation,
      enhanced localized adherence, and abolished the twitching motility-dispersal
      phase of the autoaggregation phenotype. The bfpF mutant colonized the human
      intestine but was about 200-fold less virulent. Thus, BfpF is required for
      dispersal from the bacterial aggregate and for full virulence.

PMID- 9641918
TI  - Drosophila synapse formation: regulation by transmembrane protein with Leu-rich
      repeats, CAPRICIOUS.
AB  - Upon reaching the target region, neuronal growth cones transiently search through
      potential targets and form synaptic connections with only a subset of these. The
      capricious (caps) gene may regulate these processes in Drosophila. caps encodes a
      transmembrane protein with leucine-rich repeats (LRRs). During the formation of
      neuromuscular synapses, caps is expressed in a small number of synaptic partners,
      including muscle 12 and the motorneurons that innervate it. Loss-of-function and
      ectopic expression of caps alter the target specificity of muscle 12
      motorneurons, indicating a role for caps in selective synapse formation.

PMID- 9641919
TI  - Abolition of long-term stability of new hippocampal place cell maps by NMDA
      receptor blockade.
AB  - Hippocampal pyramidal cells are called place cells because each cell tends to
      fire only when the animal is in a particular part of the environment-the cell's
      firing field. Acute pharmacological blockade of N-methyl-D-aspartate (NMDA)
      glutamate receptors was used to investigate how NMDA-based synaptic plasticity
      participates in the formation and maintenance of the firing fields. The results
      suggest that the formation and short-term stability of firing fields in a new
      environment involve plasticity that is independent of NMDA receptor activation.
      By contrast, the long-term stabilization of newly established firing fields
      required normal NMDA receptor function and, therefore, may be related to other
      NMDA-dependent processes such as long-term potentiation and spatial learning.

PMID- 9641920
TI  - Edge effects and the extinction of populations inside protected areas 
AB  - Theory predicts that small populations may be driven to extinction by random
      fluctuations in demography and loss of genetic diversity through drift. However,
      population size is a poor predictor of extinction in large carnivores inhabiting
      protected areas. Conflict with people on reserve borders is the major cause of
      mortality in such populations, so that border areas represent population sinks.
      The species most likely to disappear from small reserves are those that range
      widely-and are therefore most exposed to threats on reserve borders-irrespective
      of population size. Conservation efforts that combat only stochastic processes
      are therefore unlikely to avert extinction.

PMID- 9641921
TI  - Insecticidal toxins from the bacterium Photorhabdus luminescens.
AB  - Transgenic plants expressing Bacillus thuringiensis (Bt) toxins are currently
      being deployed for insect control. In response to concerns about Bt resistance,
      we investigated a toxin secreted by a different bacterium Photorhabdus
      luminescens, which lives in the gut of entomophagous nematodes. In insects
      infected by the nematode, the bacteria are released into the insect hemocoel; the
      insect dies and the nematodes and bacteria replicate in the cadaver. The toxin
      consists of a series of four native complexes encoded by toxin complex loci tca,
      tcb, tcc, and tcd. Both tca and tcd encode complexes with high oral toxicity to
      Manduca sexta and therefore they represent potential alternatives to Bt for
      transgenic deployment.

PMID- 9641922
TI  - All changed, changed utterly. British medicine will be transformed by the Bristol
      case.

PMID- 9641923
TI  - Central venous catheters-time for a change?. If you put them in properly you
      don't need to change them routinely.

PMID- 9641924
TI  - Controversy in managing patients with prostate cancer. Banish dogma, get more
      data.

PMID- 9641925
TI  - Taking precautions with ACE inhibitors. A theoretical risk exists in patients
      with unilateral renal artery stenosis.

PMID- 9641926
TI  - Improving doctor-patient communication. Not an option, but a necessity.

PMID- 9641927
TI  - Annual league tables of mortality in neonatal intensive care units: longitudinal
      study. International Neonatal Network and the Scottish Neonatal Consultants and
      Nurses Collaborative Study Group.
AB  - OBJECTIVE: To assess whether crude league tables of mortality and league tables
      of risk adjusted mortality accurately reflect the performance of hospitals.
      DESIGN: Longitudinal study of mortality occurring in hospital. SETTING: 9
      neonatal intensive care units in the United Kingdom. SUBJECTS: 2671 very low
      birth weight or preterm infants admitted to neonatal intensive care units between
      1988 and 1994. MAIN OUTCOME MEASURES: Crude hospital mortality and hospital
      mortality adjusted using the clinical risk index for babies (CRIB) score.
      RESULTS: Hospitals had wide and overlapping confidence intervals when ranked by
      mortality in annual league tables; this made it impossible to discriminate
      between hospitals reliably. In most years there was no significant difference
      between hospitals, only random variation. The apparent performance of individual
      hospitals fluctuated substantially from year to year. CONCLUSIONS: Annual league
      tables are not reliable indicators of performance or best practice; they do not
      reflect consistent differences between hospitals. Any action prompted by the
      annual league tables would have been equally likely to have been beneficial,
      detrimental, or irrelevant. Mortality should be compared between groups of
      hospitals using specific criteria-such as differences in the volume of patients,
      staffing policy, training of staff, or aspects of clinical practice-after
      adjusting for risk. This will produce more reliable estimates with narrower
      confidence intervals, and more reliable and rapid conclusions.

PMID- 9641928
TI  - Effect of flutamide on survival in patients with pancreatic cancer: results of a
      prospective, randomised, double blind, placebo controlled trial.
AB  - OBJECTIVES: To assess whether flutamide (Drogenil), a pure androgen receptor
      blocking agent, improves survival in patients with pancreatic carcinoma and thus
      whether testosterone is a major growth factor for this tumour. DESIGN: A
      prospective, randomised, double blind placebo controlled trial. SUBJECTS: 49
      patients with a clinical diagnosis of pancreatic carcinoma. INTERVENTIONS: 24
      patients received flutamide and 25 received placebo. MAIN OUTCOME MEASURES: Death
      of the patient. RESULTS: Analysis of all patients at 6 months and 1 year showed
      14 and eight patients alive, respectively, in the flutamide group compared with
      10 and one in the placebo group. After exclusion of those patients in both groups
      who received less than 6 weeks' treatment because of advanced disease and early
      death the comparable results were 14 (88%) and eight (50%) alive in the flutamide
      group compared with 10 (50%) and one (5%) in the placebo group. Median survival
      for all patients was 8 months in the flutamide group compared with 4 months in
      the placebo group. With the 6 week exclusions median survival was 12 months
      compared with 5 months, respectively. CONCLUSIONS: This study supports the
      concept that testosterone is a growth factor for pancreatic carcinoma and that
      blockade of androgen receptors offers an appropriate new approach to treatment.

PMID- 9641929
TI  - Effectiveness of home care programmes for patients with incurable cancer on their
      quality of life and time spent in hospital: systematic review.
AB  - OBJECTIVE: To investigate whether for patients with incurable cancer
      comprehensive home care programmes are more effective than standard care in
      maintaining the patients' quality of life and reducing their "readmission time"
      (percentage of days spent in hospital from start of care till death). DESIGN:
      Systematic review. METHODS: A computer aided search was conducted using the
      databases of Medline, Embase, CancerLit, and PsychLit. The search for studies and
      the assessment of the methodological quality of the relevant studies were
      performed by two investigators, blinded from each other. Prospective, controlled
      studies investigating the effects of a home care intervention programme on
      patients' quality of life or on readmission time were included in the analyses.
      RESULTS: Only 9 prospective controlled studies were found; eight were performed
      in the United States and 1 in the United Kingdom. Their methodological quality
      was judged to be moderate (median rating 62 on a 100 point scale). None of the
      studies showed a negative influence of home care interventions on quality of
      life. A significantly positive influence on the outcome measures was seen in 2
      out of the 5 studies measuring patients' satisfaction with care, in 3/7 studies
      measuring physical dimensions of quality of life, in 1/6 studies measuring
      psychosocial dimensions, and in 2/5 studies measuring readmission time. The
      incorporation of team members' visits to patients at home or regular
      multidisciplinary team meetings into the intervention programme seemed to be
      related to positive results. CONCLUSIONS: The effectiveness of comprehensive home
      care programmes remains unclear. Given the enormity of the problems faced by
      society in caring for patients with terminal cancer, further research is urgently
      needed.

PMID- 9641930
TI  - Routine replacement of central venous catheters: telephone survey of intensive
      care units in mainland Britain.

PMID- 9641931
TI  - Questionnaire study of effect of sex and age on the prevalence of wheeze and
      asthma in adolescence.

PMID- 9641932
TI  - Seasonal variation in coronary artery disease mortality in Hawaii: observational
      study.

PMID- 9641935
TI  - Italian duels 

PMID- 9641933
TI  - Effect of educational leaflets and questions on knowledge of contraception in
      women taking the combined contraceptive pill: randomised controlled trial.
AB  - OBJECTIVE: To assess whether provision of educational leaflets or questions on
      contraception improves knowledge of contraception in women taking the combined
      contraceptive pill. DESIGN: Randomisation of women into three groups according to
      type of educational leaflet on contraceptive information. These groups were
      subdivided into two on the basis of questions on contraception asked by the
      doctor or practice nurse. The women were followed up by postal questionnaire 3
      months later. SETTING: 15 general practices in South and West region. SUBJECTS:
      636 women attending check up appointment for repeat prescription of the combined
      contraceptive pill. MAIN OUTCOME MEASURES: Knowledge of: factors causing pill
      failure, subsequent action, emergency contraception, and all the rules (pill
      rules) that apply to the contraceptive pill. RESULTS: 523 women returned
      completed questionnaires (response rate 82%). Knowledge of contraception with no
      intervention was low with only 10 (12%) women knowing all the pill rules.
      Educational intervention had a highly significant effect on knowledge of: factors
      causing pill failure (likelihood ratio chi2=22); subsequent action (21);
      emergency contraception (24); and all the pill rules (22) (P<0.01 in all cases).
      Improvement in knowledge of all the pill rules occurred with provision of the
      summary leaflet (28% knew all the rules, adjusted odds ratio 4.04, 95% confidence
      interval 1.68 to 9.75), the Family Planning Association's leaflet (27%, 3.43,
      1.45 to 8.09), and asking questions (26%, 3.03, 1.30 to 7.00). Asking questions
      in addition to provision of leaflets improved knowledge of contraception further
      for the summary leaflet (39%, 6.81, 2.85 to 16.27) but not for the Family
      Planning Association leaflet (21%, 2.58, 1.07 to 6.18). CONCLUSION: Women
      attending check ups for repeat prescriptions of the contraceptive pill should be
      provided with educational leaflets on contraception or asked relevant questions
      to help improve their knowledge of contraception. Asking questions in addition to
      providing a summary leaflet is time consuming, but results in the most knowledge
      gained.

PMID- 9641936
TI  - Non-specific but effective 

PMID- 9641934
TI  - Contracting for general practice: another turn of the wheel of history.

PMID- 9641937
TI  - Communicating the risk reduction achieved by cholesterol reducing drugs.

PMID- 9641939
TI  - Netlines 

PMID- 9641938
TI  - Evaluating information technology in health care: barriers and challenges.

PMID- 9641940
TI  - Alternative definitions 

PMID- 9641941
TI  - Tuberculosis.

PMID- 9641942
TI  - Retracing the Oregon trail: the experience of rationing and the Oregon health
      plan.

PMID- 9641943
TI  - Spectre of racism in health and health care: lessons from history and the United
      States.

PMID- 9641944
TI  - Managing demand at the interface between primary and secondary care.

PMID- 9641945
TI  - The new NHS: the octopus 

PMID- 9641946
TI  - The new NHS: No patchwork for health centres 

PMID- 9641947
TI  - Racial discrimination in distinction awards. Discrimination is probably indirect.

PMID- 9641948
TI  - Only one quarter of women with learning disability in Exeter have cervical
      screening.

PMID- 9641949
TI  - Screening for breast cancer is necessary in patients with learning disability.

PMID- 9641950
TI  - Co-proxamol is effective in chronic pain.

PMID- 9641951
TI  - Mefloquine to prevent malaria. Interpretation of study was not based on evidence.

PMID- 9641952
TI  - Passive smoking in pregnancy.

PMID- 9641953
TI  - Causes of regional differences in air pollution effects are being studied
      further.

PMID- 9641954
TI  - Six months' follow up after occupational exposure to HIV is usually long enough.

PMID- 9641955
TI  - Acute pancreatitis. Normal serum amylase does not exclude severe acute
      pancreatitis.

PMID- 9641956
TI  - Opiate detoxification under anaesthesia.

PMID- 9641957
TI  - Clinical experience and performance in final examinations. Teaching styles need
      to be reviewed to help students with inappropriate learning styles.

PMID- 9641958
TI  - Earlier study of effect on healthcare costs of preventing fatal diseases yielded
      similar results.

PMID- 9641959
TI  - Lessons of a hip failure. Registers of joint replacement operations should be set
      up.

PMID- 9641960
TI  - Cardiac surgical services in Bristol are now of high quality.

PMID- 9641962
TI  - Out of area treatments will replace ECRs 

PMID- 9641961
TI  - John parker 

PMID- 9641963
TI  - The long march 

PMID- 9641965
TI  - A profession on probation 

PMID- 9641964
TI  - There must be a better way 

PMID- 9641967
TI  - League tables are inaccurate in ranking hospital mortality outcomes 

PMID- 9641966
TI  - Fillers 

PMID- 9641969
TI  - Benefits of home care for incurable cancer are unclear 

PMID- 9641968
TI  - Flutamide improves survival in pancreatic cancer 

PMID- 9641970
TI  - Half of british ITUs routinely replace central venous catheters 

PMID- 9641971
TI  - Wheeze becomes more prevalent in girls than boys at about the age of 12 

PMID- 9641972
TI  - Knowledge about contraception can be improved through leaflets and questions 

PMID- 9641973
TI  - Macromolecular assembly and secretion across the bacterial cell envelope: type II
      protein secretion systems.
AB  - A decade ago, Pugsley and colleagues reported the existence of a large region of
      Klebsiella DNA, distinct from the Klebsiella gene encoding pullulanase, which was
      necessary for secretion of this enzyme to the cell surface in Escherichia coli
      (d'Enfert et al., 1987a,b). The pul genes it contained proved to be the tip of an
      iceberg. The sequences reported before 1992 (d'Enfert et al., 1987a,b; d'Enfert &
      Pugsley, 1989; Pugsley & Reyss, 1990; Reyss & Pugsley, 1990) included only one
      gene (pulD) that matched any sequence in the data base; a 220 amino acid residue
      segment of PulD was 32% identical with a portion of the filamentous phage-encoded
      protein, pIV. But by the time the sequence of the 18.8 kb DNA fragment that
      contained the pul genes had been completed (Possot et al., 1992), reports of sets
      of homologous genes in several species of Gram-negative plant and animal
      pathogens had appeared. For the most part, these gene clusters were cloned by
      their ability to complement mutants that produced, but failed to secrete,
      proteins normally found in the extracellular milieu; when tested, the mutants
      showed reduced pathogenicity or were totally avirulent. The secreted proteins
      included hydrolytic enzymes such as cellulase and pectinase from plant pathogens,
      and proteases and toxins from animal pathogens. The multi-gene family necessary
      for secretion of these enzymes is now known as the type II system or the main
      terminal branch (MTB) of the general secretion pathway (GSP). As summarized by
      Pugsley et al. (1997), the current tally includes type II systems from Klebsiella
      oxytoca (pul), Erwinia chrysanthemi and carotovora (out), Xanthomonas campestris
      (xps), Pseudomonas aeruginosa (xcp), Aeromonas hydrophila (exe), and Vibrio
      cholerae (eps). A second type II system (sps) necessary for deposition of the S
      layer on the cell surface in A. hydrophila is more similar to the X. campestris
      than A. hydrophila genes (Thomas & Trust, 1995). The biggest surprise has been
      the discovery of a complete set of type II secretion genes in E. coli K12. The E.
      coli genes are not expressed under normal growth conditions, and a search is
      underway to find inducing conditions and secretion substrates (Francetic &
      Pugsley, 1996). Impressive progress has already been made in defining components
      of the pathway. What remains to be understood in mechanistic detail is how this
      protein secretion system functions.

PMID- 9641974
TI  - Graded expression of Emx-2 in the adult newt limb and its corresponding
      regeneration blastema.
AB  - Amputation of a newt limb causes stump cells to organize the reformation of the
      missing structures. The phenomenon is remarkably precise in that the regeneration
      is perfect. During the first few days following amputation, the tissue proximal
      to the plane of amputation gives rise to the blastema, an area of growth composed
      of mesenchymal cells covered by a single epithelium. The blastema possesses a
      morphogenetic potential characteristic of the structures that have been
      amputated. Looking for control genes putatively involved in regeneration, we
      cloned the newt version of the mouse and human Emx-2. Its expression is
      restricted to the skin of the regeneration territories and is graded along the
      proximal-distal axis of both forelimb and hindlimb, with higher levels in distal
      regions. The regeneration blastema also show this proximal-distal graded level of
      expression with distal blastemas (mid-radius and ulna) showing higher levels of
      expression when compared to blastemas of more proximal origin (mid-humerus).
      Finally, retinoic acid proximalizes both the level of Emx-2 expression and the
      positional memory of the blastema suggesting Emx-2 may participate in pattern
      formation by specifying positional information.

PMID- 9641975
TI  - Recognition of core-type DNA sites by lambda integrase.
AB  - Escherichia coli phage lambda integrase (Int) is a 40 kilodalton, 356 amino acid
      residue protein, which belongs to the lambda Int family of site-specific
      recombinases. The amino-terminal domain (residues 1 to 64) of Int binds to "arm
      type" DNA sites, distant from the sites of DNA cleavage. The carboxy-terminal
      fragment, termed C65 (residues 65 to 356), binds "core-type" DNA sites and
      catalyzes cleavage and ligation at these sites. It has been further divided into
      two smaller domains, encompassing residues 65 to 169 and 170 to 356,
      respectively. The latter has been characterized and its crystal structure has
      been determined. Although this domain catalyzes the cleavage and rejoining of DNA
      strands it, unexpectedly, does not form electrophorectically stable complexes
      with core-type DNA. Here we have investigated the critical features of lambda Int
      binding to core-type DNA sites; especially, the role of the central 65 to 169
      domain. To eliminate the complexities arising from lambda Int's heterobivalency
      we studied Int C65, which was shown to be as competent as Int, in binding to, and
      cleaving, core-type sites. Zero-length UV crosslinking was used to show that
      Ala125 and Ala126 make close contact with bases in the core-type DNA.
      Modification by pyridoxal 5'-phosphate was used to identify Lys103 at the protein
      DNA interface. Since both of the identified loci are in the central domain, it
      was cloned and purified and found to bind to core-type DNA autonomously and
      specifically. The synergistic roles of the catalytic and the central, or core
      binding (CB), domains in the interaction with core-type DNA are discussed for
      (Int and related DNA recombinases.

PMID- 9641976
TI  - Perturbation of nucleosome structure by the erythroid transcription factor GATA
      1.
AB  - The ability of transcription factors to gain access to their sites in chromatin
      requires the disruption or displacement of nucleosomes covering the promoter,
      signalled by the generation of a nuclease hypersensitive site. We characterise
      here the alterations in nucleosome structure caused by binding of the erythroid
      factor GATA-1 to a nucleosome carrying GATA-1 sites. DNase I and micrococcal
      nuclease probes show that GATA-1 binding causes extensive, cooperative breakage
      of the histone/DNA contacts to generate a complex very similar to that formed by
      the factor with free DNA. The only region which differs is confined to about 50
      bp surrounding the nucleosome dyad axis which appears to be the domain of
      residual contact between the DNA and histone octamer. Despite considerable
      breakage of the histone/DNA contacts, the complex is completely stable in
      solution, and disruption of the nucleosome is entirely reversible: it is
      regenerated quantitatively upon removal of the transcription factor. Moreover,
      the histone 2A/2B component of the octamer does not exchange to external
      competitor. We suggest that formation of this complex may be a step in the
      generation of a fully hypersensitive site in vivo over regulatory elements
      containing GATA family binding sites.

PMID- 9641977
TI  - Non-nearest neighbor effects on the thermodynamics of unfolding of a model mRNA
      pseudoknot.
AB  - The upstream autoregulatory mRNA leader sequence of gene 32 of 17 T-even and
      related bacteriophages folds into a simple tertiary structural motif, a hairpin
      type RNA pseudoknot. In phage T4, the pseudoknot is contained within 28
      contiguous nucleotides which adopt a pseudocontinuous helical structure derived
      from two coaxially stacked helical stems of four (stem 1) and seven (stem 2) base
      pairs connected by two inequivalent single-stranded loops of five and one
      nucleotide(s). These two loops cross the minor and major grooves of stems 1 and
      2, respectively. In this study, the equilibrium unfolding pathway of a 35
      nucleotide RNA fragment corresponding to the wild-type and sequence variants of
      the T4 gene 32 mRNA has been determined through analysis of dual-wave-length,
      equilibrium thermal melting profiles via application of a van't Hoff model based
      on multiple sequential, two-state transitions. The melting profile of the wild
      type RNA is well-described by two sequential melting transitions over a wide
      range of magnesium concentration. Compensatory base-pair substitutions
      incorporated into helical stems 1 and 2 were used to assign the first low
      enthalpy, moderate tm melting transition to the denaturation of the short three
      to four base-pair stem 1, followed by unfolding of the larger seven base-pair
      stem 2. We find that loop 1 substitution mutants (A10 to G10, C10, U10 or GA10)
      strikingly uncouple the melting of stems 1 and 2, with the U10 substitution and
      the GA10 loop expansion more destabilizing than the G10 and C10 substitutions. A
      significant increase in the extent of cleavage by RNase T1 following the
      conserved G26 (the 3' nucleotide in loop 2) in the U10, G10, and GA10 mutants
      suggests that an altered helix-helix junction region in this mutant may be
      responsible, at least in part, for this uncoupling. In addition to a modest
      destabilization of stem 2, the major effect of deletion or nucleotide
      substitution in the 3' single-stranded tail is a destabilization of stem 1, a non
      nearest neighbor tertiary structural effect, which may well be transmitted
      through an altered loop 1-core helix interaction. In contrast, truncation of the
      5' tail has no effect on the stability of the molecule.

PMID- 9641978
TI  - Combinatorial selection of a small RNA that induces amplification of IncFII
      plasmids in Escherichia coli.
AB  - Cellular RNAs play fundamental roles as genetic messages, structural components
      and, in some cases, as catalytic agents. The ability to create vast combinatorial
      libraries of random RNA sequences has previously been exploited in vitro to
      identify RNA aptamers with desirable binding specificities, and to isolate RNAs
      with novel catalytic properties. Despite the advantages of in vitro selections
      from RNA libraries, there is no way to predict if the identified RNAs can
      function in living cells. We are therefore exploring random RNA expression
      libraries in Escherichia coli to search for small RNAs with novel functions. Here
      we describe selections that identified a small RNA (approximately 260
      nucleotides) capable of altering the copy-number control circuitry of IncFII
      plasmids. The novel RNA appears to function by annealing to a region of the mRNA
      encoding the plasmid replicator protein. The resulting RNA-RNA hybrid permits
      translation of the replicator protein, but blocks base-pairing with a natural
      negative regulatory RNA. Implications of this in vivo selection strategy are
      discussed.

PMID- 9641979
TI  - A nickel complex cleaves uridine in folded RNA structures: application to E. coli
      tmRNA and related engineered molecules.
AB  - To gain more insight about Escherichia coli tmRNA structure, NiCR, a square
      planar macrocyclic nickel (II) complex, was used to probe guanine N7 exposure. On
      the basis of this additional structural information, a refined secondary
      structure of the molecule is proposed. In addition to its known specificity for
      guanine N7, we show here that the chemical probe can also cleave at specific
      uridine residues. In contrast to the alkaline-labile modification of guanine, the
      reactivity of NiCR at these uridine residues results in direct strand scission.
      To better characterize the uridine cleavage sites and assess the importance of
      the RNA structure for the reaction to occur, smaller RNA molecules derived from
      one pseudoknot (PK4) of E. coli tmRNA containing two uridine cleavage sites were
      engineered and probed. It is shown that this pseudoknot can fold by itself in
      solution and that the expected uridine residues are also cleaved by the nickel
      complex, suggesting that only a local sequence and/or structural context is
      required for cleavage. In E. coli tmRNA, the five uridine cleavage sites are
      located in double-stranded regions. These sites contain a G-U wobble base-pair
      and a downstream uridine which is cleaved. Using smaller RNAs derived from one
      stem of PK4, systematic changes in the proposed recognition motif indicate that
      the G-U pair is required for cleavage. Furthermore, there is no cleavage if the G
      U pair is reversed. If the recognition motif is moved within the stem, the
      cleavage site moves accordingly. Additionally, if the recognition motif is
      changed such that the G-U pair is flanked by two uridine residues, the reactivity
      occurs only at the 3' uridine. Radical quenching studies have indicated that
      sulfate radical, as in the case of guanine oxidation, is involved in uridine
      oxidation. Although additional studies are required to better characterize the
      reaction, this paper reports a novel specificity for a chemical probe which may
      be useful for investigating structural motifs involving G-U pairs in folded RNAs.

PMID- 9641980
TI  - Epitopes fused to F-pilin are incorporated into functional recombinant pili.
AB  - In order to develop a system which allows infection by an epitope-specific phage
      antibody via an F-pilus expressing that epitope, a study on the expression of
      foreign sequences on F-pilin was undertaken. Initially, a plasmid library was
      constructed with random sequences encoding one to five amino acid residues fused
      to the C terminus of F-pilin (traA) which was used to complement an F-plasmid
      with an amber mutation in traA. Functional F-pilin fusions were detected using
      the filamentous phage, fUSE2, which transduces tetracycline resistance, as well
      as immunoblots using a monoclonal antiserum specific for the acetylated N
      terminus of pilin. All the clones selected expressed the pilin-fusions and
      displayed full sensitivity towards fUSE2 infection, which was indistinguishable
      from the wild-type F-pilin. The sequences of fUSE2-sensitive clones when compared
      to randomly selected clones which were not fUSE2-sensitive, revealed no obvious
      pattern in the amino acid residues fused to the C terminus, except for a
      preference for a hydrophilic amino acid at position +1. Mutating the C-terminal
      Leu in wt (wild-type) pilin to Ser blocked pilus assembly and fUSE2 infection;
      the pilin was correctly processed but the level of acetylation at the N terminus
      appeared to decrease. Fusing a known epitope (myc) directly to the C terminus
      blocked processing of F-pilin leading to loss of F-pilus assembly and function.
      The introduction of random sequences between traA and this epitope yielded fully
      recombinant, functional F-pili but this appeared to be due to processing of the
      extension by an unidentified protease leading to loss of the epitope. Surface
      expression of another epitope (G2-10) was clearly demonstrated by immuno-electron
      microscopy of pili with a G2-10 monoclonal antibody. A different five amino acid
      residue spacer between the F-pilin C terminus and the G2-10 epitope produced a
      system that was transfer-proficient and fUSE2-sensitive, but the pili were barely
      detectable by immunoblots or by electron microscopy. While the underlying rules
      that govern successful epitope expression at the C terminus of F-pilin remain
      elusive, many types of foreign sequences can be displayed with varying degrees of
      success. Our results also suggest that pilin sequence determines a number of
      steps in the complex pathway for pilus assembly.

PMID- 9641981
TI  - Identification of protein-protein interactions of the major sperm protein (MSP)
      of Caenorhabditis elegans.
AB  - In nematodes, sperm are amoeboid cells that crawl via an extended pseudopod.
      Unlike those in other crawling cells, this pseudopod contains little or no actin;
      instead, it utilizes the major sperm protein (MSP). In vivo and in vitro studies
      of Ascaris suum MSP have demonstrated that motility occurs via the regulated
      assembly and disassembly of MSP filaments. Filaments composed of MSP dimers are
      thought to provide the motive force. We have employed the yeast two-hybrid system
      to investigate MSP-MSP interactions and provide insights into the process of MSP
      filament formation. Fusions of the Caenorhabditis elegans msp-142 gene to both
      the lexA DNA binding domain (LEXA-MSP) and a transcriptional activation domain
      (AD-MSP) interact to drive expression of a lacZ reporter construct. A library of
      AD-MSP mutants was generated via mutagenic PCR and screened for clones that fail
      to interact with LEXA-MSP. Single missense mutations were identified and mapped
      to the crystal structure of A. suum MSP. Two classes of mutations predicted from
      the structure were recovered: changes in residues critical for the overall fold
      of the protein, and changes in residues in the dimerization interface. Multiple
      additional mutations were obtained in the two carboxy-terminal beta strands, a
      region not predicted to be involved in protein folding or dimer formation. Size
      fractionation of bacterially expressed MSPs indicates that mutations in this
      region do not abolish dimer formation. A number of compensating mutations that
      restore the interaction also map to this region. The data suggest that the
      carboxy-terminal beta strands are directly involved in interactions required for
      MSP filament assembly.

PMID- 9641982
TI  - A general module for RNA crystallization.
AB  - Crystallization of RNA molecules other than simple oligonucleotide duplexes
      remains a challenging step in structure determination by X-ray crystallography.
      Subjecting biochemically, covalently and conformationally homogeneous target
      molecules to an exhaustive array of crystallization conditions is often
      insufficient to yield crystals large enough for X-ray data collection. Even when
      large RNA crystals are obtained, they often do not diffract X-rays to resolutions
      that would lead to biochemically informative structures. We reasoned that a well
      folded RNA molecule would typically present a largely undifferentiated molecular
      surface dominated by the phosphate backbone. During crystal nucleation and
      growth, this might result in neighboring molecules packing subtly out of
      register, leading to premature crystal growth cessation and disorder. To overcome
      this problem, we have developed a crystallization module consisting of a normally
      intramolecular RNA-RNA interaction that is recruited to make an intermolecular
      crystal contact. The target RNA molecule is engineered to contain this module at
      sites that do not affect biochemical activity. The presence of the
      crystallization module appears to drive crystal growth, in the course of which
      other, non-designed contacts are made. We have employed the GAAA
      tetraloop/tetraloop receptor interaction successfully to crystallize numerous
      group II intron domain 5-domain 6, and hepatitis delta virus (HDV) ribozyme RNA
      constructs. The use of the module allows facile growth of large crystals, making
      it practical to screen a large number of crystal forms for favorable diffraction
      properties. The method has led to group II intron domain crystals that diffract X
      radiation to 3.5 A resolution.

PMID- 9641983
TI  - Dynamical behavior of the HIV-1 nucleocapsid protein.
AB  - The HIV-1 nucleocapsid protein (NC) contains two CCHC-type zinc knuckle domains
      that are essential for genome recognition, packaging and infectivity. The
      solution structure of the protein has been determined independently by three
      groups. Although the structures of the individual zinc knuckle domains are
      similar, two of the studies indicated that the knuckles behave as independently
      folded, non-interacting domains connected by a flexible tether, whereas one study
      revealed the presence of interknuckle NOE cross-peaks, which were interpreted in
      terms of a more compact structure in which the knuckles are in close proximity.
      We have collected multidimensional NMR data for the recombinant, isotopically
      labeled HIV-1 NC protein, and confirmed the presence of weak interknuckle NOEs.
      However, the NOE data are not consistent with a single protein conformation. 15N
      NMR relaxation studies reveal that the two zinc knuckle domains possess different
      effective rotational correlation times, indicating that the knuckles are not
      tumbling as a single globular domain. In addition, the 1H NMR chemical shifts of
      isolated zinc knuckle peptides are very similar to those of the intact protein.
      The combined results indicate that the interknuckle interactions, which involve
      the close approach of the side-chains of Phe16 and Trp37, are transitory. The
      solution behavior of NC may be best considered as a rapid equilibrium between
      conformations with weakly interacting and non-interacting knuckle domains. This
      inherent conformational flexibility may be functionally important, enabling
      adaptive binding of NC to different recognition elements within the HIV-1 psi-RNA
      packaging signal.

PMID- 9641984
TI  - Multiple open forms of ribose-binding protein trace the path of its
      conformational change.
AB  - Conformational changes are necessary for the function of bacterial periplasmic
      receptors in chemotaxis and transport. Such changes allow entry and exit of
      ligand, and enable the correct interaction of the ligand-bound proteins with the
      membrane components of each system. Three open, ligand-free forms of the
      Escherichia coli ribose-binding protein were observed here by X-ray
      crystallographic studies. They are opened by 43 degrees, 50 degrees and 64
      degrees with respect to the ligand-bound protein reported previously. The three
      open forms are not distinct, but show a clear relationship to each other. All are
      the product of a similar opening motion, and are stabilized by a new, almost
      identical packing interface between the domains. The changes are generated by
      similar bond rotations, although some differences in the three hinge segments are
      needed to accommodate the various structural scenarios. Some local repacking also
      occurs as interdomain contacts are lost. The least open (43 degrees) form is
      probably the dominant one in solution under normal conditions, although a mixture
      of species seems likely. The open and closed forms have distinct surfaces in the
      regions known to be important in chemotaxis and transport, which will
      differentiate their interactions with the membrane components. It seems certain
      that the conformational path that links the forms described here is that followed
      during ligand retrieval, and in ligand release into the membrane-bound permease
      system.

PMID- 9641985
TI  - Role of main-chain electrostatics, hydrophobic effect and side-chain
      conformational entropy in determining the secondary structure of proteins.
AB  - The physiochemical bases of amino acid preferences for alpha-helical, beta
      strand, and other main-chain conformational states in proteins is controversial.
      Hydrophobic effect, side-chain conformational entropy, steric factors, and main
      chain electrostatic interactions have all been advanced as the dominant physical
      factors which determine these preferences. Many attempts to resolve the
      controversy have focused on small model systems. The disadvantage of such systems
      is that the amino acids in small molecules are largely exposed to the solvent. In
      proteins, however, the amino acids are in contact with the solvent to a different
      degree, causing a large variability of strengths of all interactions. The
      estimates of mean strengths of interactions in the actual protein environment are
      therefore essential to resolve the controversy. In this work the experimental
      protein structures are used to estimate the mean strengths of various
      interactions in proteins. The free energy contributions of the interactions are
      implemented into the Lifson-Roig theory to calculate the helix and strand free
      energy profiles. From the profiles the secondary structures of proteins and
      peptides are predicted using simple rules. The role of hydrophobic effect, side
      chain conformational entropy, and main-chain electrostatic interactions in
      determining the secondary structure of proteins is assessed from the abilities of
      different models, describing stability of secondary structures, to correctly
      predict alpha-helices, beta-strands and coil in 130 proteins. The three-state
      accuracy of the model, which contains only the free energy terms due to the main
      chain electrostatics with 40 coefficients, is 68.7%. This accuracy is approaching
      to the accuracy of currently the best secondary structure prediction algorithm
      based on neural networks (72%); however, many thousands of parameters have to be
      optimized during the training of the neural networks to reach this level of
      accuracy. The correlation coefficient between the calculated and the experimental
      helix contents of 37 alanine based peptides is 0.91. If the hydrophobic and the
      side-chain conformational entropy terms are included into the helix-coil
      transition parameters, the accuracy of the algorithm does not improve
      significantly. However, if the main-chain electrostatic interactions are excluded
      from the helix-coil and strand-coil transition parameters, the accuracy of the
      algorithm reaches only 59.5%. These results support the dominant role of the
      short-range main-chain electrostatics in determining the secondary structure of
      proteins and peptides. The role of the hydrophobic effect and the side-chain
      conformational entropy is small.

PMID- 9641986
TI  - Behavioural and hormonal responses of the pied flycatcher to environmental
      stressors.
AB  - I investigated the effects of high plasma levels of corticosterone in male pied
      flycatchers, Ficedula hypoleuca, during the period of territorial establishment
      and the nestling period. In a second experiment males were exposed to a
      territorial intruder, a great spotted woodpecker model and a weasel model during
      the nest-building and nestling periods and their behavioural and hormonal
      reactions studied. Males were also exposed to handling stress (hormonal study)
      during these periods. During the period of territorial establishment,
      corticosterone-treated males, as well as control males, abandoned the territory
      in which they were captured; however, males in both groups very soon established
      new territories. During the nestling period, corticosterone-treated males, but
      not control males, abandoned their nests. During the nest-building period, intact
      males frequently attacked the territorial intruder but corticosterone-treated
      males never did; the woodpecker was only rarely attacked by intact males, and the
      weasel never. During the nestling period, the weasel was not attacked and
      territorial intruders only rarely; but woodpeckers were frequently attacked. With
      the progress of the breeding season, male flycatchers significantly reduced their
      sensitivity, in terms of the adrenocortical response, to all stressors tested.
      During the nest-building period, corticosterone levels were significantly higher
      in males exposed to handling, a weasel and a territorial intruder than in
      unmanipulated males; corticosterone levels in males exposed to a woodpecker did
      not differ from those in unmanipulated males; and testosterone levels were
      significantly elevated in males exposed to a woodpecker and to an intruder, but
      were reduced in males exposed to a weasel. Handling did not affect the
      testosterone level. During the nestling period, all groups showed low
      testosterone levels, and only exposure to a weasel and to handling increased
      corticosterone levels significantly. The results indicate that environmentally
      induced changes in testosterone and corticosterone secretion can be affected
      independently from one another, and that there are ecological bases for the
      differentiated hormonal responses to stress. Copyright 1998 The Association for
      the Study of Animal Behaviour. Copyright 1998 The Association for the Study of
      Animal Behaviour.

PMID- 9641987
TI  - Mate guarding and risk assessment by male mountain baboons during inter-troop
      encounters.
AB  - Aggressive herding of females is a frequent but not invariant response by male
      savannah baboons, Papio cynocephalus, to encounters with other troops. While
      males in some troops are consistently more likely to herd than those in others,
      not all inter-troop encounters result in herding, even within particular troops.
      This suggests that males assess the risk of male invasion posed by each encounter
      and respond accordingly. We used data from baboon troops in the Drakensberg
      mountains to determine the rules males follow in deciding whether to herd.
      Consistent differences between troops were explained only by the adult sex ratio.
      Males were more likely to herd if the sex ratio of their own troop was female
      biased, a finding that is concordant with the observation that males are more
      likely to immigrate into troops where the sex ratio is more female biased than
      the population average. Differences within troops were a consequence only of
      encounter distance, with herding being more likely at closer distances. We found
      a negative correlation between the angle of approach to the other troop and the
      subsequent angle of deflection. We interpret this to mean that herding functions
      to increase the distance between the interacting troops, thereby curtailing
      opportunities for strange males to inspect the troop and determine its sex ratio.
      In this way, possibly unlike those in other populations, the decision rules of
      these male baboons are geared to protecting longer-term reproductive prospects.
      Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1997
      The Association for the Study of Animal Behaviour.

PMID- 9641988
TI  - Interactions between cleaning gobies and territorial damselfish on coral reefs.
AB  - We studied the interactions between cleaning gobies, Elacatinus spp., at cleaning
      stations and territorial dusky damselfish, Stegastes fuscus, on a Barbadian
      fringing reef to enhance our understanding of the behavioural impact of cleaning
      stations on members of a coral reef community. Cleaning stations within
      damselfish territories were visited by significantly fewer species and fewer
      individuals than those outside damselfish territories. At cleaning stations
      within damselfish territories, the main client was the territory holder itself.
      Client behaviour did not differ between the two types of cleaning station;
      however, cleaning gobies at stations within damselfish territories spent less
      time cleaning clients, their cleaning bouts were shorter, and their feeding rate
      on clients was slower. These effects appear to be due to the repeated aggression
      of territorial damselfish towards fish intruding on to their territories to visit
      cleaning stations. The overlap between a territorial damselfish and a cleaning
      station therefore appears to have detrimental impacts on cleaning goby foraging.
      The presence of cleaning stations within damselfish territories exerted some
      effects on the territory owners. Although the rates of intrusions were similar on
      territories with and without cleaning stations, damselfish with cleaning stations
      tended to chase intruders more often, had a lower foraging rate, and were at
      higher risk of egg predation because of increased intrusions by egg predators. A
      potential benefit to territorial damselfish is regular access to a cleaning
      station; however, the magnitude of this benefit is unknown. This study reveals
      that damselfish, which are ubiquitous on coral reefs, can generate significant
      variation in levels of use of cleaning stations, which leads to new questions
      relating to the settlement behaviour of both cleaning gobies and damselfish.
      Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998
      The Association for the Study of Animal Behaviour.

PMID- 9641989
TI  - Direct homing behaviour in the ant Tetramorium caespitum (Formicidae,
      Myrmicinae).
AB  - Direct homing refers to the behaviour whereby an ant with food runs in an almost
      straight line to the nest. We determined whether non-polarized light acts as a
      directional cue in the direct homing behaviour of the grass ant, Tetramorium
      caespitum. We carried out tests (1) under a blue sky or in total overcast
      conditions in the field, and (2) with a view of the sun or with a non-polarized
      light within a box in the laboratory. The ants' paths were recorded, and then
      analysed by means of circular and linear statistics. Ant workers with food were
      able to home directly under a blue sky, under totally overcast skies, and even
      under non-polarized lighting. In a fifth test we displaced the ants at the
      beginning of the homing trip; they returned to the presumed nest location along a
      path that ran parallel to the true homing vector, as if they had not been
      displaced. The results suggest that the ants home by dead reckoning, that is,
      they can measure directional changes and distances travelled during the outward
      trip, and integrate them into a mean home vector for direct homing depending on
      an external light-based reference system, that is, either the polarized skylight
      pattern or non-polarized lighting. Copyright 1998 The Association for the Study
      of Animal Behaviour. Copyright 1998 The Association for the Study of Animal
      Behaviour.

PMID- 9641990
TI  - Adopting adoption.
AB  - The common occurrence of adoption among birds and mammals presents evolutionary
      biologists with an explanatory challenge. The benefits to adoptees are self
      evident, but the benefits to the adopter(s), the origin of the set of behaviours
      that constitute 'adoptive' behaviour, and the conditions for its spread in
      populations are not always clear. Explanations in terms of direct and indirect
      benefits to adopters and adoptees, and in terms of conflict between them have
      been suggested to account for the current functions and the evolutionary origin
      of 'adoptive' behaviour. In this paper we emphasize one aspect of the parenting
      behaviour associated with adoption that has been neglected: we suggest that
      adoption in birds and mammals is a route for the transfer of learnt information
      through social learning of patterns of behaviour, including styles of parenting.
      By using simple models we show that learning parenting from non-parents may
      provide additional opportunities for the spread of the 'adoptive' behaviour
      itself, even when it has no selective advantage. We also offer an additional
      explanation for the adaptive significance of adoption for both adopters and
      adoptees. Our 'match-making' hypothesis suggests that in some cases, by adopting
      foreign young, parents provide their genetic young with future ecologically
      compatible, but genetically unrelated, mates. Copyright 1998 The Association for
      the Study of Animal Behaviour. Copyright 1998 The Association for the Study of
      Animal Behaviour.

PMID- 9641991
TI  - How mixed-species foraging flocks develop in response to benefits from
      observational learning.
AB  - We created experimental situations where observers (great tit, Parus major and
      marsh tit, P. palustris) acquired one of five types of experience near
      conspecific and non-conspecific demonstrators: (1) neither demonstrator was
      feeding; (2) only the conspecific was feeding; (3) only the non-conspecific was
      feeding; (4) both were feeding and the observer received a reinforcement (food)
      near the conspecific; and (5) as (4), but the reinforcement was given near the
      non-conspecific. After each treatment, we recorded whether the observer
      approached a caged conspecific or a caged non-conspecific. There was a baseline
      preference for approaching conspecifics but this could be overcome by learnt
      associations so that the birds would then approach non-conspecifics. When there
      was an opportunity to distinguish between successful and unsuccessful foragers
      (demonstrators), and the successful forager was not conspecific, observers of the
      dominant species approached the successful subordinate non-conspecifics.
      Observers of the subordinate species approached the dominant species only if they
      had received a food reinforcement near them. Observers followed non-conspecific
      individuals more often at temperatures below than above 0 degreesC and chose a
      conspecific individual more often above than below 0 degreesC. Copyright 1998 The
      Association for the Study of Animal Behaviour. Copyright 1998 The Association for
      the Study of Animal Behaviour.

PMID- 9641992
TI  - Singing and mating success in water pipits: one specific song element makes all
      the difference.
AB  - Positive correlations between male vocalization and reproductive success have
      been documented for many animal species. They are usually based on differences
      between males in vocalization rate, duration or repertoire size. Here, we present
      probably the first field study linking differences in territorial overlap and
      mating status to differences in a single, clearly definable song element, the
      'Snarr'. Male water pipits, Anthus spinoletta, with high Snarr scores were mated
      more often than males with low scores, and their territories overlapped less with
      those of neighbours. Although correlating positively with male body condition,
      the frequency of the Snarr did not reflect male age, territory size, territory
      quality in terms of food and paternal performance. Therefore, it seems unlikely
      that the higher mating success of males with high Snarr scores results from
      active female choice of high-quality males; rather, high Snarr scores seem to
      signal dominance in males. Likely mechanisms that produce the link between
      vocalization and mating success, and potential costs that prevent some males from
      producing the Snarr at a higher rate, are discussed. Copyright 1998 The
      Association for the Study of Animal Behaviour. Copyright 1998 The Association for
      the Study of Animal Behaviour.

PMID- 9641993
TI  - High population density in bank voles stimulates food hoarding after breeding.
AB  - The effects of conspecific density (i.e. risk of intraspecific competition) on
      hoarding behaviour were studied in breeding pairs of bank voles, Clethrionomys
      glareolus. I simulated high population density by using odours of conspecifics,
      to exclude the direct effects of exploitation or interference competition for
      food. The pairs of bank voles hoarded only at the end of their breeding season.
      Hoarding was not correlated with whether the voles had a litter during the
      experiment or their litter size, but was more likely at the high population
      density and for pairs with small females. This may indicate that smaller females
      especially make caches in the autumn, possibly to ensure better winter survival
      under high population density. I discuss the hoarding behaviour of bank voles in
      relation to their territorial behaviour and food resources during the breeding
      season and predictable population changes during winter. Copyright 1998 The
      Association for the Study of Animal Behaviour. Copyright 1998 The Association for
      the Study of Animal Behaviour.

PMID- 9641994
TI  - Statistical models of transitive and intransitive dominance structures.
AB  - We present an approach based on generalized linear models for analysing dominance
      data. First, dominance is defined as a parameter characterizing the relationship
      between two individuals, determining the expected number of successes of the
      first individual in disputes with the other. Second, models known from the
      literature of two different forms of transitivity are defined in terms of these
      parameters, and examples of different tests of these models are given. Third, a
      new model is developed where the traits of individuals involved in the dominance
      interactions are included as covariates. Finally, we show how two forms of
      intransitive models of dominance structures can be constructed by including a
      certain interaction term between the trait variables, and terms taking into
      account the effect of relatedness between the individuals in the group. We
      reanalyse several data sets in the literature, and also discuss Appleby's method
      (1983, Anim. Behav., 31, 600-608), which is frequently used in analysis of
      dominance data. Copyright 1998 The Association for the Study of Animal Behaviour.
      Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9641995
TI  - Male potential reproductive rate influences mate choice in a bushcricket.
AB  - Male bushcrickets, Requena verticalis, provide their mates with a proteinaceous
      nuptial gift, which functions both as paternal investment in offspring and to
      ensure sperm transfer. When nutrients are limited, males have a lower potential
      reproductive rate than females, so the operational sex ratio becomes female
      biased. Males are then expected to discriminate more in their choice of mate for
      two reasons: (1) the relatively higher female potential reproductive rate should
      reduce the costs of rejecting a female; (2) multiple mating by females should
      increase variance in female mate quality, because of first male sperm precedence.
      Males are known to discriminate against old females, which are more likely to
      have mated previously. Our objective in this study was to partition
      experimentally the influences of male potential reproductive rate (manipulated by
      diet) and variance in female quality (estimated by age) and to assess their
      relative influence on the level of mate choice of male bushcrickets. The
      potential reproductive rate of males had a great impact on their choosiness,
      whereas variance in female age had no effect. These results support recent
      theoretical models that predict costs, rather than benefits, will primarily
      influence the level of mate choice. Copyright 1998 The Association for the Study
      of Animal Behaviour. Copyright 1998 The Association for the Study of Animal
      Behaviour.

PMID- 9641996
TI  - Male parental care, differential parental investment by females and sexual
      selection.
AB  - Males play a variable parental role in reproduction, ranging from no male
      parental care to extensive male care. Females may acquire either direct or
      indirect fitness benefits from their mate choice, and direct fitness benefits
      include male parental care. Theoreticians have traditionally emphasized direct
      fitness benefits to females in species with extensive male parental care. We
      review the literature and show extensive variation in the patterns of male care,
      related to the attractiveness of males to females. At one extreme of this
      continuum, females invest differentially in parental care, investing more when
      paired with attractive males. The costs of female parental care and other aspects
      of parental investment may be balanced by benefits in terms of more attractive
      sons and/or more viable offspring. At the other extreme, in species with
      extensive direct fitness benefits, males with preferred sexual phenotypes provide
      the largest relative share of parental care. A comparative study of birds
      revealed that the extent of the differential female parental investment was
      directly related to the frequency of extra-pair paternity. Since extra-pair
      paternity may arise mainly as a consequence of female choice for indirect fitness
      benefits, this result supports our prediction that differential parental
      investment is prevalent in species where females benefit indirectly from their
      mate choice. The consequences for sexual selection theory of these patterns of
      male care in relation to male attractiveness are emphasized. Copyright 1998 The
      Association for the Study of Animal Behaviour. Copyright 1998 The Association for
      the Study of Animal Behaviour.

PMID- 9641997
TI  - Tibial coloration, fluctuating asymmetry and female choice behaviour in the
      damselfly Platycypha caligata.
AB  - The territorial damselfly Platycypha caligata (Odontata: Chlorocyphidae) has a
      courtship behaviour where males wave the white anterior surface of all six
      laterally enlarged tibiae at females. I experimentally altered this white tibial
      surface using black paint to determine the effect on male behaviour of a 25%
      reduction in area, or an increase in asymmetry between the left and right side of
      the body. I collected behavioural data on courtship, mating and fighting for
      males already holding territories. Neither a reduction in the area nor an
      increase in asymmetry of tibial whiteness affected male mating rate, courtship
      rate or fighting behaviour. These manipulations also had no significant effect on
      the daily presence at the study site. Males whose tibial whiteness was
      experimentally removed also showed no decrease in mating rate or change in
      fighting behaviour while territorial. The complete removal of tibial whiteness
      did, however, lead to a significant reduction in daily presence, possibly due to
      a reduced ability to acquire or hold a territory. There was no relationship
      between natural levels of asymmetry in tibial whiteness and mating rate, courting
      rate or fighting behaviour for males with territories. However, the natural area
      of tibial whiteness was significantly positively related to both mean male mating
      rate and copulation duration for territorial males. This result suggests that a
      phenotypic correlate of area of tibial whiteness, probably body size, is sexually
      selected through female choice among males that already hold
      territories.Copyright 1998 The Association for the Study of Animal Behaviour.
      Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9641998
TI  - Beaver response to recurrent alien scents: scent fence or scent match?
AB  - By repeatedly presenting an alien scent to territory-owning beavers, Castor
      canadensis, we tested two competing hypotheses about the function of scent
      marking: scent fence and scent matching. The scent-fence hypothesis predicts that
      territory owners should respond increasingly strongly over time towards a
      recurrent alien scent because of the ineffectiveness of previous responses. The
      scent-matching hypothesis predicts that the intensity of response should be the
      same or decrease because, without the presence of the intruding signaller coupled
      with the chemical signal, the presence of the scent itself does not advertise the
      ownership of a territory. The response level of resident beaver families was
      stable to strangers' anal gland secretions (AGSs) and decreased to strangers'
      castoreum during a period of 6 days. These results support the scent-matching
      hypothesis but not the scent-fence hypothesis. Copyright 1998 The Association for
      the Study of Animal Behaviour. Copyright 1998 The Association for the Study of
      Animal Behaviour.

PMID- 9641999
TI  - Song learning in brood-parasitic indigobirds Vidua chalybeata: song mimicry of
      the host species.
AB  - Brood-parasitic village indigobirds, Vidua chalybeata, were bred in captivity and
      foster-reared by their normal host, red-billed firefinch, Lagonosticta senegala,
      or by an experimental foster species, Bengalese finch, Lonchura striata. Male
      indigobirds reared by Bengalese finches developed the songs of Bengalese finches,
      and males reared by firefinches developed songs of firefinches. Males copied
      their foster father only when they had lived with him long after independence (45
      days post-fledging), while males separated normally at independence (22-24 days
      post-fledging) copied songs of other individuals and not songs of their foster
      father. Males reared by Bengalese finches showed no preference to learn firefinch
      song over songs of the experimental foster species or other control finch species
      even when they had lived with firefinches as companions from the time of fledging
      to independence. Males copied several song themes, acquired the same number of
      mimicry songs, and acquired their songs at the same age, whether reared by
      Bengalese finches or by firefinches. When they lived with other indigobirds, the
      male indigobirds copied mimicry songs of male indigobirds that mimicked the same
      foster species. We predicted mimicry-song specificity and repertoire size in
      experimental indigobirds from a hypothesis of an early developmental period when
      young indigobirds focus their attention on their foster parents, and a later
      period when they direct their attention to other birds with similar songs. The
      predictions, based on field observations of wild birds, were that (1) males
      reared by a novel foster species other than the normal host would learn the song
      of that foster species, and (2) males that left their foster parents at the
      normal time of independence would copy the songs of other individuals, including
      other adult indigobirds that mimicked the same foster species. Begging calls of
      young indigobirds did not mimic the calls of young firefinches. Indigobirds
      reared alone, or with young of the normal host or of the experimental foster
      species, all developed begging calls in adult song that resembled their own
      begging as nestlings and fledglings, and only males that heard other adult
      indigobirds with firefinch-mimicry begging developed firefinch begging in their
      song. The incorporation of the innate begging calls as well as the learned
      begging calls into adult song, and the modification of the song themes of their
      individual song models, suggest that song development involves processes in
      addition to copying the songs of their own foster species and of older adult male
      indigobirds with songs like their own foster parents. Copyright 1998 The
      Association for the Study of Animal Behaviour. Copyright 1998 The Association for
      the Study of Animal Behaviour.

PMID- 9642000
TI  - How mothers influence the development of litter-mate preferences in Belding's
      ground squirrels.
AB  - We performed three experiments to examine the role of mothers in the development
      of litter-mate preferences in captive juvenile Belding's ground squirrels,
      Spermophilus beldingi. First, when observed in the absence of mothers, juveniles
      did not play preferentially with litter-mates, which suggests that mothers
      somehow influence the ontogeny of litter-mate preferences. Second, when mothers
      were present but unable to intervene in social interactions, juveniles displayed
      litter-mate preferences, which suggests that mothers do not influence their
      offsprings' social development by directly intervening in social interactions. In
      another group, mothers were removed daily, a few hours before nocturnal
      immergence, and returned the following morning. Juveniles in this group did not
      display litter-mate preferences and at night they occupied burrows with many more
      non-litter-mates than litter-mates. These results suggest that associating with
      non-litter-mates can compromise the development of litter-mate preferences, and
      implies that mothers indirectly influence social development by affecting the
      identities of sleeping partners. Third, newly emergent juveniles that interacted
      only with litter-mates for 3 days in the absence of mothers subsequently
      preferred litter-mates over non-litter-mates as play partners. This result
      demonstrates that once litter-mate preferences are instilled, due in part to
      social experiences during juveniles' initial days above-ground, the preferences
      are expressed even in the absence of mothers. Collectively, the results
      demonstrate that the presence of S. beldingi mothers is important to juvenile
      social development, but that mothers do not actively direct the ontogeny of their
      offsprings' social relationships. Copyright 1998 The Association for the Study of
      Animal Behaviour. Copyright 1998 The Association for the Study of Animal
      Behaviour.

PMID- 9642001
TI  - Future value and patch choice in least chipmunks.
AB  - Animals subsisting on non-renewing patches confront a unique valuation problem,
      in which the objective value of a patch is inversely related to the amount
      already harvested. We investigated whether the subjective patch valuations of
      captive least chipmunks, Tamias minimus, reflected this environmental constraint
      as they foraged for buried patches of seeds. On the day following partial
      depletion of two patches, chipmunks spontaneously selected the least depleted
      patch, despite having no direct information about its former or present value.
      These findings held across experiments in which the order and extent of patch
      depletion were under the forager's control or experimental control. The animals
      consistently chose sites from which they had taken the fewest items, despite
      experiencing no difference in relative capture rate, suggesting that they
      discounted patch value on the basis of amount harvested or harvest time.
      Furthermore, the animals refused to return to patches they had completely
      depleted, and when induced to re-dig depleted patches by placing seeds above
      them, the animals chose randomly despite a three-fold difference in the number of
      items previously taken from each, suggesting that they disregarded rewards taken,
      attending only to the amount remaining. Subsequent experiments showed that
      chipmunks can take past reward history into account. When we refilled previously
      depleted patches and induced chipmunks to re-dig and deplete them again, they
      treated the patches as renewable types and represented their value in terms of
      the amount removed, not the amount left. Thus, the assessment mechanism of least
      chipmunks is facultative: they expect that patches will not replenish, but are
      prepared for exceptions. Copyright 1998 The Association for the Study of Animal
      Behaviour. Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9642002
TI  - An abrupt transition in colony founding behaviour in the ant Messor pergandei.
AB  - Transitions in behaviour across a continuous distribution of organisms can
      provide valuable information on how variation in behaviour is maintained. We used
      analyses developed for interspecific hybrid zones to examine geographic variation
      in colony founding strategy in the desert seed-harvester ant, Messor pergandei.
      Newly mated females initiate new colonies either alone (haplometrosis) or
      cooperatively with other foundresses (pleometrosis). The incidence of these
      founding strategies were surveyed across the species' range and found to occur in
      geographically distinct regions joined by a narrow transition zone. Foundresses
      collected from haplometrotic sites were more likely to display aggression and
      found solitary nests than foundresses from pleometrotic sites, suggesting that
      geographical variation in metrosis is due to genotypic divergence. Foundresses
      from transitional sites were generally not aggressive and tended to co-found
      nests in the laboratory, yet rarely formed associations in the field. Such an
      abrupt shift in behaviour indicates that variation in colony founding strategy is
      maintained by selection rather than the result of secondary contact of neutral
      characters. Level of aggression displays a wider cline than founding strategy and
      is likely under selection only when accompanied by active strategy preference.
      Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998
      The Association for the Study of Animal Behaviour.

PMID- 9642003
TI  - Geographical variation in agonistic behaviour in a ring species of salamander,
      Ensatina eschscholtzii.
AB  - Ensatina eschscholtzii is a plethodontid salamander with several geographical
      races distributed in a ring-like series throughout the coastal mountains and
      inland Sierra Nevada mountains of California. Populations of these salamanders
      show genetic and morphological divergence, and in this study, we examined
      divergence in overt aggressive, passive aggressive/exploratory, avoidance and
      sensory behaviours in four populations. Two of the populations represent a zone
      of secondary contact between coastal and inland lineages of Ensatina. We recorded
      behaviour of resident salamanders paired with same-sex intruders during the non
      courtship season. The residents' behaviour was affected independently by the
      population of the resident and the population of the intruder but not by the
      interaction between the resident population and the intruder population. Levels
      of agonistic and sensory behaviour showed a high degree of constraint among the
      populations. These behaviours also showed divergence among coastal and inland
      populations, and the geographical variation in behaviour is consistent with the
      phylogenetic history of Ensatina. Convergent evolution of behaviour appears to
      have occurred at the zone of secondary contact between the coastal and inland
      lineages. Variation in agonistic and sensory behaviour among the populations
      observed and between the sexes suggests that there may be geographical and sexual
      variation in territoriality or competition. Copyright 1998 The Association for
      the Study of Animal Behaviour. Copyright 1999 The Association for the Study of
      Animal Behaviour.

PMID- 9642004
TI  - The energetic cost of begging behaviour in nestling house wrens.
AB  - This study presents data relevant to the hypothesis that the energy expenditure
      associated with begging influences the signalling of need by nestling birds. We
      used open-circuit respirometry to measure the energy costs of resting, begging
      and non-begging activities in nestling house wrens, Troglodytes aedon, ranging in
      age from 1 to 11 days post-hatching. Across all ages, begging caused a 27%
      increase in metabolism above resting rates. The metabolic rate during begging was
      not related to begging vigour. However, more vigorous begs were longer and so
      required a greater total energy expenditure. We analysed videotapes of broods for
      nestling behavioural time budgets which were combined with the metabolic data and
      data on growth at different ages to generate daily energy budgets. Over a 24-h
      period, the cumulative energy allocated to begging was slight, ranging from 0.02%
      of the energy budget in younger nestlings (3 days old) to 0.22% in older ones (10
      days old). In contrast, non-begging movements accounted for 2 and 9% of the daily
      energy budget of younger and older nestlings, respectively. Relative to daily
      growth, the energy allocated to begging was equivalent to 0.05% (younger
      nestlings) and 2.3% (older nestlings) of the energy sequestered in new tissue,
      whereas the values for non-begging activities were 5.1 and 96.8%, respectively.
      These results suggest that the energetic cost of begging is not likely to have a
      substantial role in influencing communication of need by nestlings. Copyright
      1998 The Association for the Study of Animal Behaviour. Copyright 1998 The
      Association for the Study of Animal Behaviour.

PMID- 9642005
TI  - Stabilizing and directional preferences of female Hyla ebraccata for calls
      differing in static properties.
AB  - Female frogs of many species show preferences for calls with particular
      properties. This study focuses on female preferences in Hyla ebraccata for
      computer-synthesized calls that differ in pulse-repetition rate or dominant
      frequency. Both of these call properties are static acoustic properties of
      advertisement calls of H. ebraccata (within-male coefficient of variation <5%).
      Females exerted directional selection on dominant frequency, preferring low
      frequency calls (2960 Hz) to calls with the dominant frequency of the population
      mean (3240 Hz). Because size is negatively correlated with dominant frequency,
      female choice could explain size-biased mating success observed in natural
      populations. Females also exerted stabilizing selection on pulse-repetition rate,
      preferring calls with a pulse-repetition rate of the population mean (99 Hz) to
      calls with a pulse-repetition rate that was twice as fast (200 Hz). The results
      of this study show that female choice creates either directional or stabilizing
      selection on static properties of calls. Copyright 1998 The Association for the
      Study of Animal Behaviour. Copyright 1998 The Association for the Study of Animal
      Behaviour.

PMID- 9642006
TI  - Sex recognition and mate choice by male western toads, Bufo boreas.
AB  - In field-based choice experiments, we examined sex recognition and mate choice in
      male western toads, Bufo boreas. When given a simultaneous choice between a male
      and a female of equal size, males did not discriminate between the sexes and
      attempted to amplex a male or a female with equal frequency. When a test male
      clasped a stimulus male, the stimulus male uttered a release call that caused the
      test male to release the stimulus male. Male-male amplexus never lasted more than
      3 s, but male-female amplexus was tenacious and prolonged. Furthermore, males
      discriminated between gravid females that differed in body size, choosing larger
      gravid females over smaller ones, but they did not discriminate between gravid
      females or non-gravid females of equal size. In choice tests that excluded
      chemical cues, males jumped more frequently towards large females than small
      ones. Given that females are significantly larger than males, selecting larger
      individuals as potential mates increases the probability that males amplex with a
      female. Copyright 1998 The Association for the Study of Animal Behaviour.
      Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9642007
TI  - Temporal manipulation of ejaculate components by newly fertilized Drosophila
      melanogaster females.
AB  - Observations of newly mated Drosophila melanogaster females suggest that females
      control the times at which components of the ejaculate cause behavioural and
      physiological changes characteristic of fertilized females. Females that were
      assayed immediately after they mated elicited as much courtship as they did when
      they were virgins, but were unreceptive to copulation. Within a few minutes of
      when they disengaged from copulation, most females performed ovipositor
      extrusion, which has been classified as a rejection behaviour, in response to
      courting males or males that had previously performed courtship. Most females
      that were assayed immediately after mating had already ovulated. The females,
      however, do not begin to lay eggs until 4-6 h after mating, at which time they
      elicit very little courtship (Scott & Richmond 1985, Anim. Behav., 33, 817-824).
      Our observations suggest that neither ovipositor extrusion nor male-synthesized
      pheromones that are transferred to females' cuticles during copulation inhibit
      males' courtship of newly fertilized females. Thus, males cannot determine that
      newly fertilized females are unreceptive to copulation. These observations also
      indicate that the failure of newly fertilized females to mate with males is not a
      consequence of the females' inability to elicit vigorous courtship. Copyright
      1998 The Association for the Study of Animal Behaviour. Copyright 1998 The
      Association for the Study of Animal Behaviour.

PMID- 9642008
TI  - Functional referents and acoustic similarity: field playback experiments with
      rhesus monkeys.
AB  - Rhesus monkeys, Macaca mulatta, on the island of Cayo Santiago, Puerto Rico
      produce one or more of five acoustically distinctive calls when they find food.
      Three of these calls ('warbles', 'harmonic arches' and 'chirps') are produced by
      individuals finding high-quality, rare food items, whereas the other two calls
      ('coos' and 'grunts') are produced upon encountering lower-quality, common food
      items, and in non-food contexts as well. To determine how rhesus classify such
      acoustic variation, I conducted habituation experiments using a subset of the
      five call types. I designed experiments to reveal whether classification is based
      primarily on acoustic features or on the basis of a call's functional referent;
      caller identity was held constant within sessions. Habituation to 'warbles'
      transferred to 'harmonic arches', and vice versa. Thus, although these two calls
      are acoustically distinctive, they appeared to be perceptually clustered into one
      category based on referential similarities. In contrast, habituation to 'grunts'
      was followed by dishabituation to 'warbles' or 'harmonic arches', and habituation
      to 'warbles' or 'harmonic arches' was followed by dishabituation to 'grunts'.
      Dishabituation could be due to acoustic or referential differences.
      Significantly, the magnitude of the dishabituating response was asymmetric and
      depended upon the call type used in the habituation series. Thus, when subjects
      were habituated to 'grunts', they responded significantly more to tests of
      'warbles' or 'harmonic arches' than when the sequence was reversed. These results
      suggest that for rhesus monkey food-associated calls, referential differences
      carry more weight during perceptual classification than do acoustical
      differences. Copyright 1998 The Association for the Study of Animal Behaviour.
      Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9642009
TI  - Prey availability and selective foraging in shorebirds.
AB  - Accurate measurements of prey availability are vital to our understanding of
      foraging behaviour, particularly prey selectivity. In the present study,
      observations of shorebirds foraging for fiddler crabs on intertidal mudflats
      demonstrate that prey availability depends both on the temporal variation in crab
      activity and on the crabs' responses to the presence of foraging shorebirds. Our
      results suggest that measurements of prey availability that do not specifically
      account for prey activity patterns and their responses to predators are
      neccessarily inaccurate. Furthermore, our results also show that tests for
      foraging selectivity are extremely sensitive to the way in which prey
      availability is measured and can even indicate active prey selectivity when more
      accurate measures of prey availability show predators to be non-selective.
      Because inaccurate measures of food resources greatly reduce our ability to
      detect food preferences, greater care must be taken to account for prey activity
      patterns and their responses to predators in measurements of prey availability.
      Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998
      The Association for the Study of Animal Behaviour.

PMID- 9642010
TI  - Dominance between booby nestlings involves winner and loser effects.
AB  - Two-chick broods of the blue-footed booby, Sula nebouxii, ordinarily exhibit
      stable dominance-subordinance, with the senior (first-hatched) chick habitually
      aggressive and the junior one habitually submissive (Nelson 1978, The Sulidae:
      Gannets and Boobies. London: Oxford University Press). But are both the
      subordinate and the dominant chick affected in their agonistic tendencies by
      early social experience? To answer this, we permanently paired subordinate and
      dominant chicks, 2-3 weeks old, with singletons (chicks lacking experience with a
      nestmate) by cross-fostering. During the first 4 h after pairing, subordinate
      chicks were seven times less aggressive than singletons and twice as likely to be
      submissive; dominant chicks were six times as aggressive as singletons. Although
      most subordinates consistently lost agonistic encounters during the first 10 days
      after pairing, the proportion of dominants that won decreased progressively
      until, by day 6, only about half of dominant chicks were winning. Early social
      experience has a strong but reversable training effect on both subordinates and
      dominants. Training as a subordinate showed more persistent effects than training
      as a dominant, possibly in part because our testing situation perpetuated
      subordinate training and counteracted dominant training. Copyright 1998 The
      Association for the Study of Animal Behaviour. Copyright 1998 The Association for
      the Study of Animal Behaviour.

PMID- 9642011
TI  - Moult speed predicts pairing success in male harlequin ducks.
AB  - The bright plumage of male ducks in sexually dichromatic species is thought to
      have evolved through intense sexual selection. This study examined the
      relationship between the timing and speed of moult into this bright plumage and
      subsequent mating success of male harlequin ducks, Histrionicus histrionicus.
      Males that moulted relatively slowly had a lower chance of establishing a pair
      bond than others. The timing of moult was unrelated to whether a male obtained a
      mate. Moult speed and timing were not correlated within individual males, but
      were significantly repeatable in individual males over 2 years. Moult speed
      probably reflects the condition of males, whereas timing of moult is more likely
      to be related to the distance to an individual's breeding area, which determines
      the timing of arrival to the moulting grounds. In waterfowl species that have
      been studied, males usually form dominance hierarchies before pairing and females
      tend to choose dominant males. We suggest that male harlequin ducks that moult
      slowly are poor-quality individuals, which are relegated to subordinate status
      and are unlikely to attract a mate the following autumn. Copyright 1998 The
      Association for the Study of Animal Behaviour. Copyright 1998 The Association for
      the Study of Animal Behaviour.

PMID- 9642012
TI  - Estimating ancestral states of a communicative display: a comparative study of
      Cyclura rock iguanas.
AB  - In this study we describe the signature headbob displays of seven of the eight
      extant species of Cyclura iguanas using data collected from the field and from
      captive animals. We used phylogenetic comparative methods to estimate the
      ancestral states of several measures of the headbob displays, including number of
      headbobs and the duration of headbobs and inter-bob pauses. Divergence in the
      headbob display among species has been substantial, with some major changes
      occurring within only a few (about six) generations. Otherwise, results are
      consistent with those obtained previously for other lizards which suggest that
      there is an evolutionary limit on the total duration of headbob displays.
      Differences in the results obtained using different phylogenetic methods suggest
      that although estimates of ancestral states are reasonably robust to violations
      of evolutionary assumptions, we cannot determine the standard errors of those
      ancestral phenotypes accurately without more detailed information about the types
      of forces (e.g. selection, drift) underlying evolutionary change in these traits.
      In particular, within-species variation had a substantial impact on the standard
      errors of estimated ancestral states, and should be included in such estimations
      whenever possible. Finally, our results emphasize the importance of conserving
      behavioural as well as genetic diversity in trying to preserve endangered species
      for possible reintroduction into the wild. Copyright 1998 The Association for the
      Study of Animal Behaviour. Copyright 1998 The Association for the Study of Animal
      Behaviour.

PMID- 9642013
TI  - The influence of tail autotomy on agonistic behaviour in a territorial
      salamander.
AB  - Assessment of potentially asymmetrical characters (such as fighting ability and
      resident advantage) is often important in determining the outcome of agonistic
      interactions. Loss of body parts, a predator defence mechanism used by many
      animals, may lead to a reduction in fighting ability and may be easily assessed
      by competitors. We investigated the influence of tail loss on the expression of
      agonistic behaviour in the territorial red-backed salamander, Plethodon cinereus.
      Residents and intruders were matched for body size, and pairs were tested in all
      combinations of tailed or tailless residents with tailed or tailless intruders.
      Neither residents nor intruders altered their behaviour based on their own tail
      condition, but they did alter their behaviour based on the tail condition of
      their opponents. Intruders showed more aggression or less submission towards
      tailless residents than towards tailed residents. When contests were between
      residents and intruders of the same tail condition (both tailed or tailless),
      intruders were more aggressive towards residents when both were tailless than
      when both were tailed, indicating that tail loss does not directly hamper
      aggressive displays. In contests where the asymmetry between residents and
      intruders was small (based on tail condition and residency status), intruders
      showed more aggression and less submission than in contests where the asymmetry
      was large. Residents did not differ in their behaviour for most comparisons.
      Thus, for intruders, the tail condition of residents is an important determinant
      of agonistic behaviour displayed in territorial contests. For residents, factors
      other than tail condition (such as resource value) may be more likely to
      influence their behaviour. Copyright 1998 The Association for the Study of Animal
      Behaviour. Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9642014
TI  - Greater spear-nosed bats discriminate group mates by vocalizations.
AB  - Individuals often benefit from identifying their prospective social partners.
      Some species that live in stable social groups discriminate between their group
      mates and others, basing this distinction on calls that differ among individuals.
      Vocalizations that differ between social groups are much less common, and few
      studies have demonstrated that animals use group-distinctive calls to identify
      group mates. Female greater spear-nosed bats, Phyllostomus hastatus, live in
      stable groups of unrelated bats and give audible frequency, broadband calls
      termed screech calls when departing from the roost and at foraging sites.
      Previous field observations suggested that bats give screech calls to coordinate
      movements among group members. Prior acoustic analyses of 12 acoustic variables
      found group differences but not individual differences. Here, we use the same
      acoustic variables to compare calls from three cave colonies, and find that calls
      differ between caves. We also report results from field and laboratory playback
      experiments designed to test whether bats use acoustic differences to
      discriminate calls from different colonies, groups or individuals. Results from
      field playbacks indicate that response depends on the cave of origin, indicating
      that bats can discriminate among calls from different caves. This discrimination
      ability may be based, in part, on whether calls are familiar or unfamiliar to the
      listening bats. Laboratory playbacks demonstrate that bats discriminate calls
      given by their group mates from calls given by other bats from the same cave
      irrespective of familiarity. However, these experiments provide no evidence that
      bats discriminate among individuals. Previous field work indicates that females
      that forage with social group mates may benefit from shared information about
      food or mutual defence of feeding sites. Indicating group membership is
      essential, since these benefits appear to be restricted to group mates. Copyright
      1998 The Association for the Study of Animal Behaviour. Copyright 1998 The
      Association for the Study of Animal Behaviour.

PMID- 9642017
TI  - Contents of Volume 55
AB  - No Abstract Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9642018
TI  - Semantic factors in verb retrieval: an effect of complexity.
AB  - Aphasic patients often have more difficulty retrieving verbs than nouns. We
      present data from eight aphasics demonstrating that they have a selective
      impairment for verb retrieval. We then explore the role of semantic complexity
      (i.e., the number of semantic features) in verb retrieval using a delayed
      repetition/story completion task. The results indicate that six of the patients
      are better at retrieving semantically complex verbs (e.g., run) than semantically
      simpler verbs (e.g., go). The results have implications for accounts of the
      noun/verb dissociation in aphasia, as well as for theories of verb
      representation.

PMID- 9642019
TI  - Cognitive mechanisms for processing nonwords: evidence from Alzheimer's disease.
AB  - Repetition and reading of various types of pronounceable nonwords (pseudowords)
      was examined in patients with probable Alzheimer's disease (AD) and healthy
      elderly controls. Overall accuracy of performance was lower in AD patients
      compared to controls, but the two groups showed qualitatively similar response
      patterns when reading different kinds of pseudowords aloud and when repeating
      pseudowords composed of familiar phonological forms, analogous to those in real
      English words. AD patients diverged in performance from controls, however, when
      repeating pseudowords composed of phonologically unusual forms. These results
      support two conclusions: (1) Aspects of phonological processing may become
      disrupted in AD patients in association with increasing dementia severity, while
      orthographic processing remains comparatively less impaired. (2) The results are
      consistent with the view that the processing of pseudowords is achieved through
      the same system as real words, and further show that the influence of prior
      language experience on the processing of novel linguistic forms occurs primarily
      at the level of phonological, rather than orthographic processing.

PMID- 9642020
TI  - Selective kana jargonagraphia following right hemispheric infarction.
AB  - A strongly right-handed Japanese man showed an unusual writing disorder
      associated with Broca-type aphasia after suffering a right hemispheric
      infarction. Writing with his right hand produced a fluent output in contrast to
      his nonfluent speech. The patient's agraphia disproportionately affected the
      writing of kana (Japanese syllabograms), leaving relatively intact the writing of
      kanji (Japanese ideograms). His kana agraphia, consisting of substitutions,
      intrusions, transpositions, and deletions, became apparent as the number of
      syllables in target words increased. Quantitative analysis of the substitutions
      in terms of their phonological similarity to the target revealed that most of the
      substitutions were phonologically dissimilar. Those errors were distributed
      almost identically for familiar and novel words. Moreover, the errors were
      observed asymmetrically across the target: more errors occurred near the end than
      at the beginning of a word. The kana agraphia in association with fluent writing
      output resulted in kana jargonagraphia. These observations suggest that our
      patient's selective kana jargonagraphia is best explained by selective damage to
      the hypothesized kana graphemic buffer and by disinhibition of the motor engrams
      of writing behavior, both of which resulted from right hemispheric damage.

PMID- 9642021
TI  - The contribution of attentional mechanisms to an irregularity effect at the
      graphemic buffer level.
AB  - This study analyzes acquired dysgraphia observed in a French-speaking woman. The
      results point to an impairment of the graphemic buffer, i.e., the processing
      stage where abstract orthographic representations are temporarily stored while
      planning the written production. However, the spelling errors were more frequent
      in the irregular than in the regular words. A qualitative analysis of the errors
      in the irregular misspelled words showed that, in general, these were not
      "regularization" errors, but rather the same characteristics as the
      phonologically implausible errors found in the regular words, such as letters
      substitutions, deletions, additions, and transpositions. Furthermore, in a list
      of regular and irregular words of same length and graphemic structure, the errors
      not only tended to concentrate on the irregularity itself but also tended to be
      more frequent elsewhere in the irregular words compared to the regular words.
      These finding are discussed in terms of a post-lexical sensitivity to irregular
      spelling. It is also shown that when focusing attention on the irregularity
      becomes necessary, this can cause a detriment to the surrounding graphemic
      constituents. Interaction between attentional resources and processing of
      orthographic representations at the graphemic buffer level is considered.

PMID- 9642022
TI  - Why does monitoring fail in jargon aphasia? comprehension, judgment, and therapy
      evidence.
AB  - Many people with jargon aphasia seem unaware of their speech disorder. The first
      section of this paper reports data from four subjects which indicate that self
      monitoring can fail even when subjects' input skills are apparently adequate to
      detect their errors. Explanations for this dissociation have attributed
      monitoring failure to a deficit in auditory feedback, or to a resource limitation
      which prevents concurrent speaking and monitoring. Section 2 reports a series of
      naming and judging experiments with one of the subjects which rule out these
      explanations. These show that the subject can detect his neologisms when he is
      repeating, but not when he is naming. These results suggest that his monitoring
      difficulties arise when he is accessing phonology from semantics. Section 3
      presents a study which supports this inference, since it shows that semantically
      focused intervention yields improvements in self-monitoring. It is concluded (1)
      that monitoring failure can arise from deficits within the production process
      which preclude comparison of actual with intended output, and (2) that this
      deficit is best explained within a connectionist model in which monitoring is
      performed by feedback mechanisms in the word production process.

PMID- 9642023
TI  - Cerebral networks and functional brain asymmetry: evidence from regional
      metabolic changes during word repetition.
AB  - Word repetition causes a significant bilateral metabolic increase in both
      superior temporal cortices. Frontal speech areas are less activated despite their
      presumable speech competence. We investigated in this study the relationship
      between frontal and temporal cortical areas during word repetition. We measured
      regional cerebral metabolic rates of glucose (CMRGI) in 15 normal subjects with
      positron emission tomography (PET) at rest and during word repetition.
      Significant correlations connected frontal and temporal areas of both
      hemispheres, notwithstanding their different levels of mean metabolic activation.
      The left planum temporale was a hub of significant interregional correlations, in
      contrast to its contralateral mate. This study indicates that an asymmetric
      network of significant connections orchestrates the speech-relevant cortical
      areas according to the actual needs of speech processing.

PMID- 9642024
TI  - Visual half-field Stroop effects with spatial separation of words and color
      targets.
AB  - Past inconsistencies in the occurrence of differential visual half-field Stroop
      effects were addressed in two experiments using a visual half-field presentation
      technique incorporating brief displays (100 ms) and a fixation task designed to
      ensure proper eye fixation at display onset. Experiment 1 used displays in which
      distractor words and color targets were presented in contralateral visual fields.
      Experiment 2 compared contralateral with ipsilateral displays where words and
      color targets appeared one above the other in the same visual field. Stroop
      effects were larger whenever a word occupied the right as opposed to the left
      visual field, regardless of whether the color target was left or right. Results
      are consistent with the idea that words are processed more efficiently or
      automatically in right visual field/left hemisphere presentations.

PMID- 9642025
TI  - Intact higher-level constraints on the pronunciation of new written words by
      nonfluent dysphasics.
AB  - Nonfluent, Broca-type dysphasics are characterized by impaired syntactic
      processing. However, grammaticality judgements and certain on-line tasks have
      shown some preservation of this processing in such subjects. We report an
      experiment with nonfluent dysphasics in which they read aloud th-initial nonwords
      (e.g., thuz) in sentential contexts that predicted a function word or a content
      word. This paradigm was first used by Campbell and Besner (1981) to demonstrate
      syntactic effects on pronunciation: normal subjects pronounce word-initial th- as
      voiced in function word contexts and unvoiced in content word contexts,
      reflecting a regularity in the English lexicon. Poorer performance by the
      dysphasic subjects on this task is the default prediction of most "syntactic"
      accounts of agrammatism, including an account based on the impairment of
      functional projections, which we discuss. We replicate Campbell and Besner's
      effect in our normal control group and in the dysphasic group, with no
      significant difference between the two groups. We conclude that syntactic
      influences on pronunciation may be unimpaired in nonfluent dysphasia, and that
      the task used resembles the class of online tasks, in its capacity to elicit
      unimpaired processing. We argue that this result is compatible with the account
      of agrammatism discussed if the latter is grounded in a distributed, constraint
      based processing device allowing graceful degradation of functioning.

PMID- 9642027
TI  - The 'drug value' in the European pharmaceutical system.
AB  - European regulatory authorities (EMEA, European Commission) and/or national
      pharmacological and medical decision-makers can utilise the drug value to help
      themselves to decide which drugs to define as really innovative instead of new,
      which regulations to implement, which drugs to include on formularies, or which
      restrictions to enforce. As economic research becomes widely accepted for
      pharmaceutical evaluation, it needs to utilise prospective rather than
      retrospective study design. Analyses conducted at the time of therapy have better
      access to patients and can obtain both more accurate information on consumption
      of resources and the impact of pharmacotherapy on non-monetary quality of life
      for patients, survival, comparative clinical effectiveness and economic outcomes
      within social health service or in wider economy.

PMID- 9642028
TI  - Evidence-based medicine criteria applied to hypolipidemic and antihypertensive
      drug trials: is drug efficacy always the same?

PMID- 9642029
TI  - Captopril in the management of patients after acute myocardial infarctions. A
      cost effectiveness analysis in Italy.
AB  - The prevalence of acute myocardial infarction (AMI) is found in approximately
      500,000 individuals in Italy. The annual incidence can be crudely estimated to be
      100,000 events. This represents a major health care problem and generates
      questions about the rational allocation of public resources devoted to health
      care, specially since Italy has a National Health Service. We focused on the
      economics of adding captopril administration to standard care in Italy in AMI
      patients matching the entry criteria of the SAVE study. The cost effectiveness
      ratio(s) was explored under different assumptions on the effectiveness and on the
      cost of the intervention. In our base case, administering captopril has an
      incremental Cost Effectiveness Ratio of 14.708 million lira (1 US $ = 1529 lira
      in December 1996) per life year saved (LYS) (maximum range 7.171-21.003). This
      means that a net investment to the NHS of approximately 12 billion lira over 4
      years to treat 10,000 patients matching the entry criteria of the SAVE trial will
      prevent 410 cardiovascular deaths (i.e. 33.229 million lira per cardiovascular
      death prevented) and save approximately 928 (discounted) to 1027 (not discounted)
      LYS over the same time period. Results are sensitive to the cost of captopril and
      of revascularisation procedures.

PMID- 9642030
TI  - Antiallergic/antiasthmatic activity of oligopeptide related to IgE.
AB  - In spite of continuous research in the field of bronchial asthma, still no
      satisfactory drug is available. Recently a new class of oligopeptide exhibited
      antiallergic activity by inhibiting the synthesis of IgE antibody. The analogue
      of ADSDGK (94-335) has shown antiallergic activity in experimental models. The 94
      335 inhibited the passive cutaneous anaphylaxis (PCA) reactions in rats in a dose
      dependent manner (0.5-10 mg kg-1 p.o.) by 47-90%. There was a 70-87% protection
      of mast cell degranulation induced by compound 48/80 with peptide 94-335 at 0.5
      1.5 mg kg-1 p.o. in rats. This peptide also inhibited antigen- induced
      contraction in sensitised guinea pig ileum. There was 18 and 72% protection to
      bronchoconstriction induced by histamine and egg albumin, respectively, in an
      aerosol test in guinea pigs. These effects of compound 94-335 were comparable
      with that of the clinically-used antiallergic drug disodium cromoglycate (DSCG).
      The results suggest that peptide 94-335 possesses potent antiallergic activity.

PMID- 9642031
TI  - The localisations in liposomal membranes of the tetrahydrofuran ring moieties of
      the annonaceous acetogenins, annonacin and sylvaticin, as determined by 1H NMR
      spectroscopy.
AB  - The positions of the tetrahydrofuran (THF) ring moieties of annonacin (a mono-THF
      ring Annonaceous acetogenin) and sylvaticin (a non-adjacent bis-THF ring
      Annonaceous acetogenin) within liposomal membranes made of
      dimyristoylphosphatidylcholine (DMPC) were determined by proton (1H) nuclear
      magnetic resonance (NMR) spectroscopy. Based on 1H intermolecular nuclear
      Overhauser effects (NOEs), the THF rings of both acetogenins studied reside near
      the polar interfacial head group region of the DMPC. Recently, we have reported
      that the THF rings of a series of asimicin type of Annonaceous acetogenins (with
      adjacent bis-THF rings) also reside near the interfacial head group of DMPC. We
      can now conclude that the Annonaceous acetogenins, containing either mono-,
      adjacent bis-, or non-adjacent bis-THF ring moieties, have their THF ring
      moieties at the interfacial region of membranes, i.e., the THF ring moiety seems
      to serve a role as an anchor in the lipid membranes. This may be related to the
      uniquely potent bioactivities that Annonaceous acetogenins exhibit at their
      enzyme-inhibitory sites within mitochondrial and plasma membranes.

PMID- 9642032
TI  - Evidence for the stabilisation of the high-affinity state of beta-adrenoceptors
      by an endogenous factor in rat brain.
AB  - Inhibition of binding of the labelled antagonist (-)[3H]CGP 12177 by the full
      agonist (-)isoproterenol results in shallow competition curves, characteristic of
      the presence of both high- and low-affinity states of beta-adrenoceptors
      (betaAR). When in excess, the GTP analog 5'-guanylylimidodiphosphate (GppNHp) is
      expected to convert all receptors in the high-affinity state to the low-affinity
      state. However, in the rat cortex and cerebellum synaptosomes, a proportion of
      the betaAR in the high-affinity state was GppNHp-insensitive. This apparent
      GppNHp-insensitivity decreased with decreasing temperature of incubation.
      Moreover, it was totally abolished by the gentle treatment of membranes with 3
      [(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS). We propose that
      a protein factor interacts with the betaAR/Gs protein complex and that it induces
      the GppNHp-insensitivity. This factor would be released by CHAPS in a functional
      form because it may regenerate the GppNHp-insensitivity after concentration and
      reconstitution with CHAPS-treated membranes. It is likely that the factor acts as
      a stabiliser of betaAR in the high-affinity state.

PMID- 9642033
TI  - Effect of non-steroidal anti-inflammatory drugs on the anticonvulsive activity of
      valproate and diphenylhydantoin against maximal electroshock-induced seizures in
      mice.
AB  - Prostaglandins and their inhibitors may affect convulsive phenomena. Thus, the
      aim of this study was to examine possible interactions between non-steroidal anti
      inflammatory drugs and two conventional antiepileptic drugs in terms of their
      anticonvulsive activity and side-effects. Also, the plasma levels of
      antiepileptics were measured in order to delineate possible pharmacokinetic
      interactions. The following non-steroidal anti-inflammatory drugs (NSAIDs) were
      studied: acetylsalicylic acid, ibuprofen, indomethacin, metamizole, paracetamol
      and piroxicam. None of these drugs affected the threshold for electroconvulsions.
      However, all NSAIDs studied enhanced the protective activity of valproate
      magnesium against maximal electroshock-induced seizures. Only ibuprofen and
      piroxicam enhanced the anticonvulsive activity of diphenylhydantoin. Ibuprofen
      decreased the ED50 value of valproate (for the induction of motor impairment) in
      the rotorod test, whilst piroxicam reduced the ED50 value of valproate in rotorod
      and chimney tests. Diphenylhydantoin combined with either ibuprofen or piroxicam
      did not cause any motor impairment in these tests. The total plasma level of
      valproate and free plasma level of diphenylhydantoin remained unchanged in the
      presence of all studied NSAIDs. These data demonstrate that NSAIDs could enhance
      the protective activity of antiepileptics. However, in case of valproate it may
      be associated with the severe side effects.

PMID- 9642034
TI  - Differences in the effects of vasopressin and oxytocin on feline gastric corpus
      motility: selective action of vasopressin on longitudinal muscle.
AB  - The effect of vasopressin and oxytocin on the contractile activity of
      preparations isolated from the feline gastric corpus wall was investigated.
      Vasopressin (1.5 x 10(-9)-2.1 x 10(-7) M), but not oxytocin, evoked concentration
      dependent tonic contractions only of longitudinal muscle strips. At the same
      time, vasopressin (1.5 x 10(-9)-2.1 x 10(-7) M) potentiated the magnitude of
      amplitudes, but not the frequency, of spontaneous contractions. Both the
      vasopressin V1 receptor antagonist d(CH2)5-(Me)2-Tyr-AVP and the predominantly
      vasopressin V2 receptor antagonist d(CH2)5, D-Ile2, Ile4-AVP, the non-selective
      muscarinic receptor antagonist, atropine, the predominantly selective muscarinic
      M1 receptor antagonist, pirenzepine, the predominantly selective muscarinic M2
      antagonist, methoctramine, the predominantly selective muscarinic M3 receptor
      antagonist, para-fluoro-hexahydro-siladifenidol, and the calcium channel blocker,
      nifedipine, but not the ganglion blocking agent, mecamylamine, depressed or
      blocked the tonic contractions induced by vasopressin. Among the antagonists,
      only atropine and nifedipine inhibited the spontaneous contractions. On the other
      hand, the anticholinesterase, physostigmine, potentiated both the vasopressin
      induced tonic and spontaneous contractions. With regard to the receptors, the
      vasopressin-induced tonic contractions are mediated at least in part through
      vasopressin V1 and V2 receptors, non-selective muscarinic and selective
      muscarinic M1, M2 and M3 receptors. The increase in amplitudes of spontaneous
      contractions is mediated only via-nonselective muscarinic receptors. Vasopressin
      receptors appear to be located mostly pre-synaptically, although the direct
      effect of vasopressin on post-synaptic receptors cannot be excluded. The pA2
      values suggests rather V1a than V1b vasopressin receptor subtype involvement in
      tonic contractions vasopressin had produced. The tonic as well as spontaneous
      contractions are calcium-dependent. In addition, these results point to the
      existence of non-selective muscarinic receptors, which participate in the
      regulation of both tonic and spontaneous contractions, while muscarinic M1, M2
      and M3 receptors subserve only the tonic contractions.

PMID- 9642035
TI  - Response to isoproterenol of rabbit detrusor strips following exposure to NSAIDs.
AB  - To ascertain whether NSAIDs affect the physiological mechanisms involved in
      bladder detrusor muscle motility we investigated the influence of indomethacin,
      ibuprofen and acetyl salicylic acid on the beta-adrenergic-evoked response in
      isolated male-rabbit detrusor strips. Incubation with indomethacin for 60 min
      significantly reduced the tissue response to isoproterenol (up to 10.8+/-4.9%),
      entirely abolished spontaneous contractions and caused a fall in basal tone.
      Ibuprofen significantly inhibited the tissue response to isoproterenol (up to
      25.5+/-5.8%), abolished spontaneous contractions and caused a fall in basal tone.
      After the spasmogen KCl had been added to restore basal tone, the highest
      indomethacin and ibuprofen concentrations still significantly inhibited the
      isoproterenol-evoked response, indomethacin being the most active compound.
      Acetyl salicylic acid, at the doses used, neither inhibited spontaneous
      contractions nor changed basal tone whereas it significantly inhibited tissue
      response to isoproterenol (up to 69. 6+/-4.6%). Our findings in rabbit detrusor
      strips show that NSAIDs affect the beta-adrenergic-evoked response. They probably
      do so mainly through mechanisms other then inhibition of prostaglandin
      production.

PMID- 9642036
TI  - Changes in the nitric oxide system of rat myometrium during midgestation and
      delivery at term.
AB  - The aims of this study were to investigate whether a nitric oxide (NO) system is
      present in the pregnant rat myometrium and whether it differentially inhibits
      myometrial contractility during midgestation and delivery at term. Myometrial
      strips were obtained from eight rats at midgestation (day 16) and eight rats
      during delivery at term, and mounted in an organ bath for assessment of isometric
      tension. There were scarce spontaneous contractions with gradually increased
      amplitude that ceased after short periods at midgestation, whereas the frequency
      of spontaneous contractions increased and were regular, and the amplitude of
      contractions became stable and long lasting during delivery. Spontaneous and
      carbachol- induced contractions were decreased by L-arginine and increased by NG
      nitro-L-arginine methyl ester (L-NAME) at midgestation and delivery, but much
      higher concentrations of L-arginine and L-NAME were required to obtain this
      effect at delivery. These results show: (1) that there is basal and carbachol
      stimulated production of NO in pregnant rat myometrium; (2) that the L-arginine
      NO system inhibits myometrial contractility; (3) that the effect of the L
      arginine-NO system is elevated at midgestation and decreased during delivery; and
      (4) that the L-arginine-NO system may contribute to uterine quiescence during
      gestation and the initiation of labour at term.

PMID- 9642037
TI  - The site of action of furosemide.
AB  - To establish whether furosemide (F) acts on the proximal tubule beside the thick
      ascending limb of Henle's loop, we reviewed the data from 55 rats studied before
      and during the i.v. infusion of 10 mg kg-1 of furosemide. These animals were the
      object of previously published studies. SNGFR was 42.6+/-1.1 nl min-1 during
      baseline conditions (B), 42.7 nl min-1 during F (P>0.9). In 151 paired last
      proximal tubular samples, percentage reabsorption was 71.72 before and 71.72%
      after F (P=1.0). In 64 paired early distal tubular samples, percent reabsorption
      fell from 86% in B to 78% during F (P<0.0001). During F, the urine flow rate
      expressed as a percentage of GFR (24+/-2%) was significantly correlated (R=0.52,
      P<0.0001) with the percent delivery of filtrate out of the proximal tubule (26+/
      3%). These data demonstrate that, even at this very high dosage, F does not act
      on the proximal tubule. It inhibits transport on the ascending limb of Henle's
      loop. By allowing the delivery of isotonic tubular fluid to the distal tubule, it
      causes a fall in volume absorption along the early distal convolution in
      proportion to its baseline water permeability. It increases urine flow by
      abolishing the interstitial hypertonicity and, consequently, the osmotically
      driven solvent flow across the distal epithelium and collecting ducts. Therefore
      the urine flow rate during F closely approximates volume delivery out of the
      proximal tubule.

PMID- 9642038
TI  - Pattern of antimicrobial drug prescribing and prescriptive behaviour for acute
      otitis media among physicians in Sicily.
AB  - Acute otitis media (AOM) is one of the most common diseases of childhood, but it
      is less common in adults. Usually, in clinical practice therapy cannot wait until
      the laboratory report and the choice of an antibiotic prescription is initiated
      on an empirical basis. Moreover, several studies have shown great variability in
      antibiotic prescription for AOM. The study was carried out in order to describe
      the antibiotic prescribing pattern and the prescriptive behaviour among Sicilian
      general practitioners (GPs) in choosing an empirical antibiotic regimen for
      treatment of AOM. Each GP completed a questionnaire for each therapeutic
      intervention which ended with an antibiotic prescription. Diagnoses and drugs
      were classified according to the International Classification of Diseases (ICD
      10) and to the Anatomical Therapeutic Chemical (ATC) classification system,
      respectively. Antibiotics, issued for AOM, accounted for 11.1% of total
      antimicrobial therapy in paediatrics and 3.4% in adults. The commonest
      therapeutic groups were: cephalosporins (44.1%), macrolides (26.1%), extended
      spectrum penicillins (16.1%), combination of penicillins and beta-lactamase
      inhibitors (11.4%). The route of administration appeared to be influenced by age
      of the patients, by a subjective clinical assessment of disease severity and by
      the presence of concurrent diseases. The diagnostic criteria and the marked
      variation in antibiotic prescribing pattern for AOM among Sicilian GPs reflects a
      lack of knowledge of any local or national guidelines.

PMID- 9642039
TI  - Announcements 
AB  - Copyright 1998 The Italian Pharmacological Society .

PMID- 9642040
TI  - Identification of a phosphodiesterase I/nucleotide pyrophosphatase-related gene
      mRNA in rat vascular smooth muscle cells by the differential display approach.
AB  - Vascular smooth muscle cell hypertrophy and proliferation may participate in the
      pathophysiology of cardiovascular disease. The analysis of changes in gene
      expression in vascular smooth muscle cells is crucial to the understanding of the
      molecular biology of cardiovascular disease. An effective method for analysis of
      gene expression is the differential display approach. Applying the differential
      display approach, we identified a gp130RB13-6-related gene in vascular smooth
      muscle cells following stimulation with platelet-derived growth factor-BB and
      angiotensin II. It is well known that gp130RB13-6 is a
      phosphodiesterase/nucleotide pyrophosphatase. Northern blotting and reverse
      transcriptase-polymerase chain reaction analysis revealed a dramatic down
      regulation of the gp130RB13-6-related mRNA after six hours of stimulation of the
      cells with both agonists. Recently, gp130RB13-6 was identified as a rat neural
      differentiation and tumor cell surface plasma membrane glycoprotein. These
      findings demonstrate that the expression of gp130RB13-6 mRNA in vascular smooth
      muscle cells is remarkably regulated by growth factors and therefore may play an
      important role in the regulation of vascular smooth muscle cell growth.

PMID- 9642041
TI  - RNA polymerase mutants that destabilize RNA polymerase-promoter complexes alter
      NTP-sensing by rrn P1 promoters.
AB  - Mutations in Escherichia coli rpoB or rpoC, selected for the ability to confer
      prototrophy on relA spoT strains, were found to affect transcription from rrn P1
      promoters. Two mutant strains (beta RH454 and beta' delta 215-220) reduced
      transcription of rrn P1 core promoter-lacZ fusions but not of control promoter
      lacZ fusions. Purified mutant RNAPs formed complexes with rrn P1 promoters that
      were much less stable than those formed by wild-type RNAP and required high
      concentrations of the initiating NTP for efficient rrn P1 transcription. The
      instability of the rrn P1 core promoter complexes with the mutant RNAPs and their
      altered regulatory properties support a recently proposed model for the control
      of rRNA transcription by changing concentrations of the initiating NTPs. We
      further suggest that destabilization of promoter complexes by the mutant RNAPs
      mimics effects of ppGpp, decreasing or increasing transcription depending on the
      kinetic properties of the specific promoter.

PMID- 9642042
TI  - Structure and NTPase activity of the RNA-translocating protein (P4) of
      bacteriophage phi 6.
AB  - The RNA polymerase complex of bacteriophage phi 6 comprises four proteins, P1,
      P2, P4 and P7, and forms the core of the virion. Protein P4 is a non-specific
      NTPase that provides the energy required for RNA translocation (packaging).
      Characterization of purified recombinant P4 shows that the protein assembles into
      stable hexamers in the presence of ADP and divalent cations. Image averaging of
      electron micrographs reveals this hexamer as a slightly skewed ring with outer
      and inner diameters of 12 and 2 nm, respectively. NTPase activity of P4 is
      associated only with the hexameric form. Ca2+ and Zn2+ and non-specific single
      stranded RNA stimulate the NTPase activity, while Mg2+ acts as a non-competitive
      inhibitor, presumably via a separate Mg2+ binding site. Binding affinities of
      different nucleotide mono-, di- and triphosphates and non-hydrolyzable analogs
      indicate that the beta-phosphate moiety is required for substrate binding. A
      slight preference for binding of purine nucleotides is also observed. Analysis of
      P4 by CD and Raman spectroscopy indicates an alpha/beta subunit fold that is
      altered only slightly by hexamer assembly. Raman markers of P4 secondary and
      tertiary structures are also largely invariant to nucleotide exchange and
      hydrolysis, suggesting that the mechanisms of RNA translocation involves movement
      of subunits relative to one another rather than large scale changes in the
      alpha/beta subunit fold. The stoichiometry of P4 in the mature phi 6 virion is
      estimated as 120 copies. Because the recombinant P4 hexamers exhibit hydrodynamic
      and enzymatic properties that are identical to those of P4 oligomers released
      from native phi 6, we propose that P4 occurs as hexamers in the native viral core
      particle.

PMID- 9642043
TI  - A toggle duplex in hepatitis delta virus self-cleaving RNA that stabilizes an
      inactive and a salt-dependent pro-active ribozyme conformation.
AB  - The antigenomic RNA of hepatitis delta virus (HDV) can form a short duplex, P2a,
      in which a four-nucleotide sequence within the self-cleaving domain pairs with a
      sequence just outside the previously defined 3'-boundary of the ribozyme. Both
      sequences that would participate in forming P2a were previously determined to be
      non-essential for self-cleavage activity. Ribozymes able to form P2a were less
      active than those lacking the 3' P2a sequence when preincubated under the
      standard low-Na+ conditions. Chemical probing of the RNA correlated base-pairing
      in P2a with this inhibition. Furthermore, mutagenesis and 3' truncation
      experiments mapped the inhibitory sequence to P2a. However, raising the NaCl
      concentration in the preincubation prior to adding Mg2+ reversed the inhibitory
      effect. Moreover, with NaCl preincubation, the P2a-containing ribozyme was more
      active than an otherwise identical ribozyme lacking the 3' P2a sequence. Non
      denaturing gels provided evidence for alternative conformations of the P2a
      containing precursor with only the faster-migrating species correlating with the
      active form. A difference in the temperature-dependence for the rate of cleavage
      of the P2a-containing ribozyme with and without NaCl, together with a difference
      in the melting behavior of the RNA in NaCl with and without P2a, suggested that
      P2a favors the native structure in NaCl. Many derivatives of the HDV ribozymes
      form inactive conformers; however, this study reveals details of a specific
      structure that stabilizes both inactive and active conformations of the HDV
      ribozyme.

PMID- 9642044
TI  - Fanconi anemia C gene product plays a role in the fidelity of blunt DNA end
      joining.
AB  - Mutations in genes controlling the correct functioning of the replicative, repair
      and recombination machineries may lead to genomic instability. A high level of
      spontaneous chromosomal aberrations amplified by treatment with DNA cross-linking
      agents is the hallmark of Fanconi anemia (FA), an inherited chromosomal
      instability syndrome associated with cancer proneness. Two of the eight FA genes
      have been cloned (FAA and FAC), but their function has not yet been defined. The
      lack of homology with known genes suggests the involvement of FA genes in a novel
      pathway specific to vertebrates. Using a DNA end-joining assay in cultured cells,
      we studied the processing of both blunt and cohesive-ended double strand breaks
      (DSB) in normal and FA cells. The results show that: (i) the overall ligation
      efficiency is normal in FA lymphoblasts; (ii) in FA-C, error-free processing of
      blunt-ended DSB is markedly decreased, resulting in a higher deletion frequency
      and larger deletion size; (iii) the fidelity of processing of blunt-DSB is
      completely restored in FACC cells (complemented with wild-type FAC gene) and the
      deletion size shifted to values similar to that observed in normal cells; (iv)
      the fidelity of cohesive end-joining is not affected in FA cells; (v) activities
      and/or expression of known factors involved in DSB processing, such as the
      components of the DNA-PK complex and XRCC4, are normal in FA cells. Our results
      provide strong evidence that the lack of a functional FAC gene results in loss of
      fidelity of end-joining, which likely accounts for the FA-C phenotype of
      chromosome instability. We conclude that FAC, and perhaps all FA gene products,
      are likely to play a role in the fidelity of end-joining of specific DSB.

PMID- 9642045
TI  - Orientation changes of fluorescent probes at five sites on the myosin regulatory
      light chain during contraction of single skeletal muscle fibres.
AB  - Changes in the orientation of the myosin regulatory light chain (RLC) in single
      muscle fibres were measured using polarised fluorescence from
      acetamidotetramethylrhodamine (ATR). Mutants of chicken skeletal RLC containing
      single cysteine residues at positions 2, 73, 94, 126 and 155 were labelled with
      either the 5 or 6-isomer of iodo-ATR, giving ten different probes. The labelled
      RLCs were exchanged into demembranated fibres from rabbit psoas muscle without
      significant effect on active force generation. Fluorescence polarisation
      measurements showed that nine out of the ten probe dipoles were more
      perpendicular to the fibre axis in the absence of ATP (in rigor) than in either
      relaxation or active contraction. The orientational distribution of the RLC
      region of the myosin head in active contraction is closer to the relaxed than to
      the rigor orientation, and is not equivalent to a linear combination of the
      relaxed and rigor orientations. Rapid length steps were applied to the fibres to
      synchronise the motions of myosin heads attached to actin. In active contraction
      the fluorescence polarisation changed both during the step, indicating elastic
      distortion of the RLC region of the myosin head, and during the subsequent rapid
      force recovery that is thought to signal the working stroke. The peak change in
      fluorescence polarisation produced by an active release of 5 nm per half
      sarcomere indicates an axial tilt of less than 5 degrees for all ten probes, if
      all the myosin heads in the fibre respond to the length step. This tilting was
      towards the rigor orientation for all ten probes, and could be explained by 14%
      of the heads moving to the rigor orientation. An active stretch tilted the heads
      away from the rigor conformation by a similar extent.

PMID- 9642046
TI  - Correlation of the expansion segments in mammalian rRNA with the fine structure
      of the 80 S ribosome; a cryoelectron microscopic reconstruction of the rabbit
      reticulocyte ribosome at 21 A resolution.
AB  - Samples of 80 S ribosomes from rabbit reticulocytes were subjected to electron
      cryomicroscopy combined with angular reconstitution. A three-dimensional
      reconstruction at 21 A resolution was obtained, which was compared with the
      corresponding (previously published) reconstruction of Escherichia coli 70 S
      ribosomes carrying tRNAs at the A and P sites. In the region of the intersubunit
      cavity, the principal features observed in the 70 S ribosome (such as the L1
      protuberance, the central protuberance and A site finger in the large subunit)
      could all be clearly identified in the 80 S particle. On the other hand,
      significant additional features were observed in the 80 S ribosomes on the
      solvent sides and lower regions of both subunits. In the case of the small (40 S)
      subunit, the most prominent additions are two extensions at the base of the
      particle. By comparing the secondary structure of the rabbit 18 S rRNA with our
      model for the three-dimensional arrangement of E. coli 16 S rRNA, these two
      extensions could be correlated with the rabbit expansion segments (each totalling
      ca 170 bases) in the regions of helix 21, and of helices 8, 9 and 44,
      respectively. A similar comparison of the secondary structures of mammalian 28 S
      rRNA and E. coli 23 S rRNA, combined with preliminary modelling studies on the 23
      S rRNA within the 50 S subunit, enabled the additional features in the 60 S
      subunit to be sub-divided into five groups. The first (corresponding to a total
      of ca 335 extra bases in helices 45, 98 and 101) is located on the solvent side
      of the 60 S subunit, close to the L7/L12 area. The second (820 bases in helices
      25 and 38) is centrally placed on the solvent side of the subunit, whereas the
      third group (totaling 225 bases in helices 18/19, 27/29, 52 and 54) lies towards
      the L1 side of the subunit. The fourth feature (80 bases in helices 78 and 79)
      lies within or close to the L1 protuberance itself, and the fifth (560 bases in
      helix 63) is located underneath the L1 protuberance on the interface side of the
      60 S subunit.

PMID- 9642047
TI  - Analysis of striated fiber formation by recombinant SF-assemblin in vitro.
AB  - The basal bodies of green flagellates are often connected to striated microtubule
      associated fibers (SMAFs), which are highly ordered bundles of 2 nm filaments. SF
      assemblin (33 kDa) is the principal structural subunit of the SMAFs and consists
      of a non-helical head domain of approximately 32 residues and an alpha-helical
      rod domain that shows a pronounced coiled-coil forming ability. To investigate
      the functional role of the head domain we expressed N-terminally truncated
      molecules using a cDNA coding for SF-assemblin from Chlamydomonas reinhardtii.
      Recombinant wild-type SF-assemblin or molecules with an N-terminal deletion of
      ten residues formed striated fibers with an axial repeat of 28 nm. N-terminal
      truncations of 19 and 29 residues yielded assembly-incompetent molecules,
      revealing that the head domain is necessary for the constitution of striated
      fibers. Further, molecules with an internal deletion of 24 residues or with
      duplicated segments corresponding to insertions of 29 and 58 residues were
      constructed. The resulting fibers had altered cross-striation patterns and axial
      repeats. The observed shifts in the axial repeat corresponded well to the number
      of inserted or deleted residues, indicating a linear coherence between molecule
      length and axial repeat. The heptad pattern of the rod domain of SF-assemblin is
      regularly interrupted by skip residues. The removal of one or two skip residues
      had no significant effect on the ultrastructure of the striated fibers.
      Substitution of skip no. 2 with alanine resulted in a modified, asymmetric cross
      striation pattern, indicating a polar architecture of the striated fibers. In
      summary, various mutations of SF-assemblin effected the solubility of the
      molecules, and the axial repeat, cross-striation pattern, or overall appearance
      of the fibers. Thus, analysis of SF-assemblin may represent a valuable system to
      study the interactions involved in the polymerization of fibrous coiled-coil
      proteins. A model of the SMAFs based on staggered protofilaments consisting of
      overlapping 36 nm subunits is presented.

PMID- 9642048
TI  - Conformational changes of the Tet repressor induced by tetracycline trapping.
AB  - The X-ray crystal structure analysis of inducer-free Tet repressor, TetR, at 2.4
      A resolution identifies one of two openings of the tunnel-like binding site as
      the entrance for the inducer tetracycline-Mg2+, [Mg Tc]+. Recognition and binding
      of the inducer unleashes conformational changes leading to the induced state of
      TetR. In the first step, the C-terminal turn of alpha-helix 6 unwinds, thereby
      altering the orientation of alpha-helix 4. This different orientation of alpha
      helix 4 is stabilized by a series of hydrogen bonds mediated through a chain of
      eight water molecules. The alpha-helix 4 connects the DNA-binding domain (alpha
      helices 1 to 3) to the rigid TetR core, and thus regulates gene expression
      through its respective orientations.

PMID- 9642049
TI  - Side-chain effects on peptidyl-prolyl cis/trans isomerisation.
AB  - Peptidyl-prolyl cis/trans isomerisation has been frequently found as a rate
      limiting step in the folding of proteins. In order to determine whether the
      nature of the amino acid preceding proline controls the probability of cis prolyl
      bonds in native proteins, systematic studies on the thermodynamics and kinetics
      of the prolyl isomerisation in the pentapeptide series Ac-Ala-Xaa-Pro-Ala-Lys-NH2
      were performed. All proteinogenic amino acids were substituted in the position
      preceding proline. When measured by 1H-NMR and CD spectroscopy both isomers
      proved to be devoid of ordered structure in the whole series of the oligopeptides
      in aqueous solution. Thus, isomerization rates and cis/trans ratios calculated
      from solvent jump and 1H-NMR magnetisation transfer experiments exclusively
      reflect the side-chain effects of the Xaa position in the peptide series. There
      is a rough correlation between the cis content in the oligopeptides and the
      propensity of Xaa-Pro cis prolyl bonds in proteins. This correlation suggests
      that the prolyl bond conformation is mainly determined by local effects in
      proteins. The rate constants kc-->t of pentapeptides containing unionised amino
      acids preceding proline range from 3.2 x 10(-3) s-1 (Xaa = Ala) to 0.5 x 10(-3) s
      1 (Xaa = Trp) at 4 degrees C. Proline clustering led to an isomerisation cycle
      indicating considerable influence on the isomerisation rates of the peptide bond
      conformations flanking the rotating bond. Both tyrosine and histidine
      specifically reduce isomerisation rates severalfold by deprotonation of their
      respective side-chains.

PMID- 9642050
TI  - The nature of ligand-induced conformational change in transferrin in solution. An
      investigation using X-ray scattering, XAFS and site-directed mutants.
AB  - Ligand-induced conformational change in transferrins has been studied by site
      directed mutagenesis of human serum half molecule (N-lobe), X-ray absorption fine
      structure (XAFS) spectroscopy and X-ray solution scattering. Use of recent
      advances in data analysis has been made for extracting model-independent
      molecular shapes from X-ray solution scattering data for the intact, the half
      molecule and its mutants. Clear evidence is provided that the transferrin
      molecule (intact as well as N-lobe), in its apo and holo forms, exists for the
      majority of the time in well-defined specific conformations representing the
      "fully opened" and "closed" states of the molecule, respectively. Evidence is
      also provided for the existence of an additional conformation, referred to here
      as the "intermediate" conformation for simplicity, which is trapped in the case
      of some of the mutants in the iron-bound form. We suggest that domain closure in
      the transferrin molecule is a two-step process, with the intermediate
      conformation representing the first stage of domain closure (approximately 20
      degrees hinge-twist of domain II). Our data are not inconsistent with the ligand
      free molecule sampling the closed states occasionally (< or = 10%) but are not in
      support of a continuous conformational search between the fully opened and closed
      states in the absence of iron.

PMID- 9642051
TI  - Structure-based redesign of the catalytic/metal binding site of Cfr10I
      restriction endonuclease reveals importance of spatial rather than sequence
      conservation of active centre residues.
AB  - According to the crystal structure of Cfr10I restriction endonuclease the acidic
      residues D134, E71 and E204 are clustered together and presumably chelate metal
      ion(s) at the active site. Indeed, investigation of the DNA cleavage properties
      of substitutional mutants of Cfr10I D134A, E71Q, E71A and E204Q reveals that
      D134, E71 and E204 residues are essential for cleavage activity, supporting their
      active site function. Structural comparison indicates that the D134 residue of
      Cfr10I spatially overlaps with aspartate residues D91 and D74, from the invariant
      active site motifs 90PDX19EAK and 73PDX15DIK of EcoRI and EcoRV, respectively.
      However, structural studies in conjunction with mutational analyses suggest that
      the sequence motif 133PDX55KX13E corresponds to the active site of Cfr10I, but
      differs from canonical active site motifs of EcoRI and EcoRV. According to the
      crystal structure of Cfr10I the serine S188 residue from the 188SVK sequence
      motif is a spatial equivalent of the acidic residue from the (E/D)XK-part of the
      active site motif, which is conserved between EcoRI and EcoRV. Site-directed
      mutagenesis experiments of Cfr10I, however, revealed that the S188 was not so
      important for catalysis while the E204 residue located 2.8 A away indeed was
      essential for cleavage, suggesting that the glutamate E204 rather than the S188
      residue contributes to the metal binding site in Cfr10I. In addition, model
      building studies suggest that mutual interchange of the E204 and S188 residues
      should lead only to minor positional differences of the carboxylate residues of
      glutamate side-chains. The double mutant S188E/E204S was therefore prepared by
      site-directed mutagenesis where the active site motif 133PDX55KX13E of Cfr10I was
      changed to a canonical motif 133PDX53EVK, which is similar to that of EcoRI and
      EcoRV. Interestingly, the double mutant S188E/E204S of Cfr10I with redesigned
      active site structure, exhibited 10% of Wt cleavage activity in a gamma DNA
      cleavage assay. Thus, structure guided redesign of the catalytic/metal binding
      site of Cfr10I, provides novel experimental evidence to suggest that spatial
      rather than sequence conservation plays the dominant role in the formation of
      restriction enzyme active sites.

PMID- 9642052
TI  - A partial hprt gene duplication generated by non-homologous recombination in V79
      Chinese hamster cells is eliminated by homologous recombination.
AB  - Here, the sequence in the hprt gene of the duplication mutant SPD8 originating
      from V79 Chinese hamster cells was determined. The duplication arose after non
      homologous recombination between exon 6 and intron 7, resulting in an extra copy
      of the 3' portion of exon 6, of exon 7 and of flanking intron regions. Only a
      duplication of exon 7 is present in the mRNA, since the duplicated exon 6 lacks
      its 5' splice site and is removed during RNA processing. The findings in this
      study suggest that the non-homologous recombination mechanism which occurred here
      may have been initiated by endonucleases, rather than by a spontaneous double
      strand break. Subsequently, 14 spontaneous SPD8 revertants with a functional hprt
      gene were isolated and characterized using PCR and sequencing. The data revealed
      that although the SPD8 cell line arose by non-homologous recombination, it
      reverts spontaneously by homologous recombination. Interestingly, the downstream
      copy of exon 7 was restored by this process. This was indicated by the presence
      of a specific mutation, a T-to-G transversion, close to the breakpoint, a
      characteristic unique to the SPD8 clone. Our results suggest that the spontaneous
      reversion of this cell line by homologous recombination may involve an exchange,
      rather than a conversion mechanism.

PMID- 9642053
TI  - New insights for dinucleotide backbone binding in conserved C5'-H . . . O
      hydrogen bonds.
AB  - Most enzymes that utilize dinucleotide NAD or NADP are known to comprise a
      glycine-rich loop segment (e.g. the GXGXXG signature motif of Rossman fold) which
      binds the cofactor's diphosphate moiety. Through analysis of a set of diverse
      NAD(P)-bound protein structures, we show here that with few exceptions this
      diphosphate binding is complemented by a second loop segment interacting from a
      different angle with unconventional yet apparently ubiquitous C-HellipsisO
      hydrogen bonds formed between C5' methylene of dinucleotide and, primarily,
      carbonyl oxygen of protein. This finding implicates an important role of C5' in
      protein-nucleotide recognition.

PMID- 9642054
TI  - Two large subunits of the fission yeast RNA polymerase II provide platforms for
      the assembly of small subunits.
AB  - The subunit-subunit contact network was analyzed for the Schizosaccharomyces
      pombe RNA polymerase II consisting of ten putative subunits. Previously we
      carried out far-Western blot analysis of bimolecular interaction with radio
      labeled subunit 3 and 5 probes. Here we extended the analysis using another six
      small-sized subunits as probes. Taking the results together the subunit-subunit
      interaction was observed for a total 18 (or 19) combinations. All eight small
      sized subunits exhibited binding activities to two large subunits, Rpb1 and Rpb2.
      In addition, bimolecular interaction was observed for the combinations of Rpb3
      Rpb5, Rpb3-Rpb11 (and Rpb5-Rpb8/11). The subunit-subunit contact within the
      assembled RNA polymerase was then analyzed by protein-protein cross-linking using
      five species of bifunctional cross-linkers with different length and specificity.
      Cross-linking was observed for a total of 19 combinations, including five
      combinations between small subunits, Rpb3-Rpb10, Rpb3-Rpb11, Rpb5-Rpb6, Rpb6-Rpb7
      and Rpb6-Rpb8. The results altogether indicate that two large subunits Rpb1 and
      Rpb2 provide the platform for assembly of small subunits and also small subunits
      interact with each other for limited combinations. Direct contact of the two
      large subunits, Rpb1 and Rpb2, was also demonstrated by cross-linking.

PMID- 9642055
TI  - Effects of reaction conditions on RNA secondary structure and on the helicase
      activity of Escherichia coli transcription termination factor Rho.
AB  - The ATPase and helicase activities of the Escherichia coli transcription
      termination protein rho have been studied under a variety of reaction conditions
      that alter its transcription termination activity. These conditions include KCl,
      KOAc, or KGlu concentrations from 50 to 150 mM and Mg(OAc)2 concentrations from 1
      to 5 mM (in the presence of 1 mM ATP). In higher KCl or higher Mg(OAc)2
      concentrations we found that the translocation of rho hexamers along RNA was
      slower and less processive than the same process measured at 50 mM monovalent
      salt concentrations and 1 mM Mg(OAc)2. The ATPase activity of rho was also
      decreased under reaction conditions that slowed translocation. RNA melting
      experiments showed that the decreased ATPase activity of rho and the slower
      helicase activity at increased KCl or Mg(OAc)2 concentrations are accompanied by
      a concomitant increase in the secondary structure of the RNA portion of the
      helicase substate. In contrast, the ATPase activity of rho in the presence of
      poly(rC), a synthetic RNA that does not form salt-concentration-dependent
      secondary structure, was shown to be the same in each of the three monovalent
      salts. Thus, the salts do not directly affect the structure or conformation of
      the rho protein or the binding of rho to single-stranded RNA. However, the
      translocation of rho along RNA was more processive in 150 mM KOAc or KGlu than in
      150 mM KCl, while the RNA secondary structure was the same in all three
      monovalent salts. Therefore, the monovalent salt present in the reaction may
      directly affect rho-RNA interactions when the RNA substrate can form secondary
      structure. Helicase experiments with an RNA molecule that does not contain a rho
      loading-site showed that rho translocates less processively along this potential
      helicase substrate. These results suggest that the helicase activity of rho may
      be significantly regulated by RNA secondary structure. In addition, one of the
      mechanisms to concentrate the activity of rho on transcripts containing
      unstructured rho loading sites may be that rho translocation along such molecules
      is more processive than it is along more structured RNA molecules in the cell.

PMID- 9642056
TI  - tRNA imbalance promotes -1 frameshifting via near-cognate decoding.
AB  - tRNAGly1 is the Escherichia coli glycine tRNA specific for GGG codons. A genetic
      selection for multicopy suppressors of a frameshift mutation has shown that
      increased levels of wild-type tRNAGly1 causes -1 frameshifting. Analysis of the
      suppression spectrum of this multicopy suppressor and peptide sequencing of the
      suppressed protein product showed that it promoted GG doublet decoding at the
      near-cognate GGA codons. It is proposed that increasing the concentration of the
      GGG-specific tRNAGly1 relative to the cognate GGA-decoding tRNAGly2 allows the
      near-cognate tRNA to read GGA codons. Near-cognate decoding of GGA codons by
      tRNAGly1 can occur by a two-out-of-three reading mechanism, in which only the
      first two bases of the GGA codon are paired with the anticodon, thus permitting
      doublet translocations. In mycoplasmas, a single tRNA typically decodes all four
      triplets of a codon family and introduction of a feature of the Mypoplasma
      mycoides tRNAGly responsible for non-discriminate decoding, a C at position 32,
      into the anticodon E. coli tRNAGly1, enhanced the efficiency of doublet decoding.

PMID- 9642057
TI  - A novel class of supercoil-independent nuclease hypersensitive site is comprised
      of alternative DNA structures that flank eukaryotic genes.
AB  - The cell makes a fundamental distinction between genes and non-gene sequences,
      which mechanistically underlies the process of gene regulation. Here, we describe
      the properties of a novel class of genetic sites that reproducibly flank and
      delineate the coding regions of the eukaryotic genes tested. Defined in vitro
      reaction conditions that include altered solvation and elevated temperature
      rendered the sites hypersensitive to nuclease cleavage. Consequently, the
      complete coding regions of the Drosophila genes tested were quantitatively
      excised from genomic DNA or genomic clones by this treatment. Identical reaction
      products were generated from linear or supercoiled DNA substrates. Chemical
      modification and fine-structure analysis of several cleavage sites flanking
      Drosophila genes showed that the cleavage sites were stable nucleic acid
      structures that contained specific arrangements of paired and unpaired
      nucleotides. The locations and properties of the cleavage sites did not
      correspond to previously known nuclease hypersensitive sites nor to known
      alternative DNA structures. Thus, they appear to represent a new class of genetic
      site. In a deletion analysis, the minimal sequence information necessary to
      direct in vitro nuclease cleavage 3' to the Drosophila GART gene co-localized
      with the signal required for termination of transcription in vivo. The data
      suggest that a novel class of DNA site with distinct structural properties
      encodes biological information by marking the boundaries of at least some gene
      expression units in organisms as diverse as Plasmodium and Drosophila.

PMID- 9642058
TI  - A superrepressor mutant of the arginine repressor with a correctly predicted
      alteration of ligand binding specificity.
AB  - Arginine biosynthesis in Escherichia coli is negatively regulated by the
      hexameric repressor protein ArgR and the corepressor L-arginine. L-Arginine binds
      to ArgR in the C-terminal domain of the repressor. Binding to operator DNA occurs
      in the N-terminal domain. The molecular structures of both domains have recently
      been elucidated. The known stereochemistry of the arginine binding pocket was
      used for the rational design of a mutant ArgR with altered ligand specificity.
      Our prediction was that a replacement of Asp128 by asparagine would
      preferentially lead to the binding of L-citrulline, rather than L-arginine. The
      D128N mutant was constructed and was shown to fulfill our expectation by several
      experimental approaches. By isothermal titration calorimetry it was found to bind
      L-citrulline much more strongly than L-arginine, in contrast to wild-type ArgR.
      Exchange between the mutant trimers of the hexamer was inhibited by L-citrulline,
      as it is by L-arginine in the wild-type. The mutant protein was precipitated by L
      citrulline but not by L-arginine, whereas the reverse is true for the wild-type
      protein. Demonstration of a corepressor action was, however, precluded by the
      superrepressor effect of the D128N mutation by itself. The mutant protein, in the
      absence of L-citrulline or L-arginine is as strong a repressor as the wild-type
      protein in the presence of L-arginine. We discuss two possible mechanisms, in
      terms of the known domain structures that could explain our observations.

PMID- 9642059
TI  - The transcriptional activator GvpE for the halobacterial gas vesicle genes
      resembles a basic region leucine-zipper regulatory protein.
AB  - The GvpE protein involved in the regulation of gas vesicles synthesis in
      halophilic archaea has been identified as the transcriptional activator for the
      promoter located upstream of the gvpA gene encoding the major gas vesicle
      structural protein GvpA. A closer inspection of the GvpE protein sequence
      revealed that GvpE resembles basic leucine-zipper proteins typically involved in
      the gene regulation of eukarya. A molecular modelling study of the C-terminal
      part implied a cluster of basic amino acid residues constituting the DNA-binding
      site (DNAB) followed by an amphiphilic helix, suitable for the formation of a
      leucine-zipper structure within a GvpE dimer. The model of a GvpE dimer docked
      onto DNA indicated that the side-chains of the basic residues could perfectly
      interact with the negatively charged phosphate groups of the DNA backbone.
      Substitution of three basic amino acid residues of this putative DNAB by alanine
      and/or glutamate generated mutated GvpE proteins. None of these was able to
      activate the c-gvpA promoter in vivo, indicating that these basic residues are
      required for GvpE activity. This identification of an archaeal gene regulator
      displaying similarity to eukaryal regulatory proteins implies that the basic
      transcription machinery of eukarya and archaea are closely related, and that the
      regulatory proteins have evolved according to common principles.

PMID- 9642060
TI  - Derivation of the three-dimensional architecture of bacterial ribonuclease P RNAs
      from comparative sequence analysis.
AB  - The secondary structure of bacterial RNase P RNA, a ribozyme responsible for the
      maturation of the 5' end of tRNAs, is well established on the basis of sequence
      comparison analysis. RNase P RNA secondary structures fall into two types, A and
      B, which share a common core formed by the assembly of two main folding domains,
      but differ in their peripheral elements.A revised alignment of 137 available
      sequences reveals new covariations allowing for the refinement of both types of
      secondary structures. Phylogenetic evidence is thus provided for the extension of
      stems P11, P14, P19, P10.1 and P15.1 through further canonical base-pairs or
      GAellipsisGA mismatches. These refinements led in turn to a new organization of
      the catalytic core, with coaxial stackings of helices P2 and P19 as well as P1
      and P4. New inter-domain tertiary interactions involve loop L9 and helix P1 and
      loop L8 with helix P4. These features were incorporated into atomic-scale 3D
      models of RNase P RNA for representatives of each structural type, namely
      Escherichia coli and Bacillus subtilis. In each model, the juxtaposition of the
      core helices creates a cradle onto which the pre-tRNA substrate binds with most
      evolutionarily conserved residues converging towards the cleavage site. The inner
      cores of both types are stabilized similarly, albeit by different peripheral
      elements, emphasizing the modular and hierarchical organisation of the
      architecture of RNase P RNAs. Similarities are thus apparent between the type A
      modules, P16/P17/P6 and P13/P14, and their type B analogs, P5.1/P15.1 and P10.
      1/P10.1a, respectively. Other noteworthy features of these models include
      compactness and good agreement with published crosslinking data.

PMID- 9642061
TI  - Branch migration through DNA sequence heterology.
AB  - Branch migration of a DNA Holliday junction is a key step in genetic
      recombination. Previously, it was shown that a single base-pair heterology
      between two otherwise identical DNA sequences is a substantial barrier to passage
      of a Holliday junction during spontaneous branch migration. Here, we exploit this
      inhibitory effect of sequence heterology to estimate the step size of branch
      migration. We also devise a simulation of branch migration through mismatched
      base-pairs to arrive at the underlying molecular basis for the block to branch
      migration imposed by sequence heterology. Based on the observation that two
      adjacent sequence heterologies exert their effects on branch migration more or
      less independently, we conclude that the step size of branch migration is quite
      small, of the order of one or two base-pairs per migratory step. Comparison of
      branch migration experiments through a single base-pair heterology with
      simulations of a random walk through sequence heterology suggests that the
      inhibition of branch migration is largely attributable to a thermodynamic barrier
      arising from the formation of unpaired or mispaired bases in heteroduplex DNAs.

PMID- 9642062
TI  - Mutational analysis of phi29 DNA polymerase residues acting as ssDNA ligands for
      3'-5' exonucleolysis.
AB  - Here, three highly conserved amino acid residues have been characterized to
      function as ssDNA binding ligands at the 3'-5' exonuclease active site of phi29
      DNA polymerase. One of these residues, Phe65, belongs to motif Exo II, previously
      described to contain an invariant aspartate and an invariant asparagine involved
      in catalysis and ssDNA binding, respectively. The other two residues, Ser122 and
      Leu123, form a newly identified motif "(S/T)Lx2h", and are the homologous
      counterparts of Pol I residues Asp457 and Met458, and of T4 DNA polymerase
      residues Ser286 and Leu287, the latter three residues shown to contact ssDNA at
      their corresponding cocrystal 3D structures. Site-directed mutagenesis and
      biochemical analysis of eight phi29 DNA polymerase mutant proteins at residues
      Phe65, Ser122 and Leu123 indicated their functional importance for: (1) a stable
      interaction with ssDNA; (2) 3'-5' exonucleolysis of ssDNA substrates; (3)
      proofreading of DNA polymerization errors. Extrapolation to the crystal
      structures of Klenow and T4 DNA polymerases indicates that the invariant aromatic
      ring contiguous to the catalytic aspartate of the Exo II motif, corresponding to
      Tyr423 in Klenow, Phe218 in T4, and Phe65 in phi29 DNA polymerase, appears to be
      critical to orient the ssDNA substrate in a stable conformation to allow 3'-5'
      exonucleolytic catalysis. This is the first time that the functional importance
      of this invariant residue, belonging to the Exo II motif, has been demonstrated.

PMID- 9642063
TI  - Analyzing the functional organization of a novel restriction modification system,
      the BcgI system.
AB  - BcgI is a novel, multi-subunit, restriction-modification (R-M) system that
      differs from all the other types of R-M system in its genetic and functional
      organization. The holoenzyme contains two different subunits, BcgI A and BcgI B.
      Both are required for endonuclease and methyltransferase activities. Here, we
      show that the endonuclease activity is mediated by the N-terminal portion of the
      A subunit. We made this assignment by mutational analysis. The analytic strategy
      involved three steps. First, the methyltransferase activity was inactivated by
      site-directed mutagenesis of a conserved methyltransferase motif also found in
      the A subunit. One of the R+M- mutants could not methylate DNA but was still able
      to cleave it, therefore expression of this mutant gene was lethal to the host.
      This lethal phenotype allowed the selective isolation of cleavage-deficient (R-)
      mutations in a second round of random mutagenesis in this mutant background. The
      R- mutations were all located in the N-terminal portion of the A subunit. There
      are five potential endonuclease motifs within this region. Conserved acidic
      residues in each of these motifs were substituted with alanine by site-directed
      mutagenesis of the wild-type A gene. The results identified one motif, P52E53
      (X)12-E66D67K68, as the probable endonuclease active-site. Further support for
      this assignment was obtained by another round of site-directed mutagenesis
      directed to residues surrounding this motif. The results showed that DNA cleavage
      activity was mediated by the predicted, conserved residues, and not any of the
      surrounding non-conserved residues. One mutant protein, BcgI-E53A, with a single
      amino acid substitution decreased the DNA cleavage activity at least 700-fold.
      Our present model for the functional organization of BcgI locates both
      endonuclease and methyltransferase domains in the A subunit, with the target
      recognition domain located in the B subunit.

PMID- 9642064
TI  - Catapult mechanism renders the chaperone action of Hsp70 unidirectional.
AB  - Molecular chaperones of the Hsp70 type promote the folding and membrane
      translocation of proteins. The interaction of Hsp70s with polypeptides is linked
      to ATP binding and hydrolysis. We formed complexes of seven different
      fluorescence-labeled peptides with DnaK, the Hsp70 homolog of Escherichia coli,
      and determined the rate of peptide release under two different sets of
      conditions. (1) Upon addition of ATP to nucleotide-free peptide.DnaK complexes,
      all tested peptides were released with similar rate constants (2.2 s-1 to 6.7 s
      1). (2) In the binding equilibrium of peptide and ATP-liganded DnaK, the
      dissociation followed one or two-step reactions, depending on the amino acid
      sequence of the peptide. For the monophasic reactions, the dissociation rate
      constants diverged by four orders of magnitude from 0.0004 s-1 to 5.7 s-1; for
      the biphasic reactions, the rate constants of the second, slower isomerization
      step were in the range from 0.3 s-1 to 0.0005 s-1. The release of the different
      peptides in case (1) is 1.4 to 14,000 times faster than in case (2). Apparently,
      binding of ATP induces a transient state of the chaperone which ejects target
      peptides before the final state of ATP-liganded DnaK is reached. This "catapult"
      mechanism provides the chaperone cycle with a mode of peptide release that does
      not correspond with the reverse of peptide binding. By allowing the conformation
      of the outgoing polypeptide to differ from that of the incoming polypeptide, a
      futile cycle with respect to conformational work exerted on the target protein is
      obviated.

PMID- 9642065
TI  - Functional properties of the molecular chaperone DnaK from Thermus thermophilus.
AB  - The genes coding for the Thermus thermophilus (Tth) homologues of the molecular
      chaperones DnaK and GrpE (DnaKTth and GrpETth) were cloned and expressed in
      Escherichia coli. The proteins were purified and their functional properties were
      assessed by equilibrium and transient kinetic methods. DnaKTth has an intrinsic
      ATPase activity of 3x10(-4) s-1 at 25 degreesC and 10x10(-4) s-1 at 75 degreesC
      under single turnover conditions. It binds the fluorescent nucleotide analogue N8
      (4-N'-methylanthraniloylaminobutyl)-8-aminoadenosine 5'-diphosphate (MABA-ADP)
      with a dissociation constant (Kd) of 3 nM and ADP with a Kd of 47 nM at 25
      degreesC. At 75 degreesC the affinities are decreased fivefold to 15 nM (MABA
      ADP) and 280 nM (ADP). The kinetic constants for two-step binding of MABA-ADP and
      of ADP to DnaKTth were determined at 25 degreesC and 75 degreesC, respectively.
      GrpETth acts as a nucleotide-exchange factor on DnaKTth and accelerates the
      release of bound MABA-ADP significantly. This shows that the nucleotide-binding
      domain is functionally intact, and that the specific interaction of DnaKTth and
      GrpETth is mediating nucleotide exchange.A fluorescently labelled peptide that
      comprises a subsequence of the E. coli transcription factor sigma32 binds to
      nucleotide-free DnaKTth with a Kd of 4.9 microM. Displacement with unlabelled
      peptide yields a Kd of 5.0 microM for the unlabelled peptide. Thus the peptide
      binding domain also appears to be functional.For the cellular chaperone function
      of DnaK, a coupling between nucleotide and peptide-binding domains is required.
      However, with DnaKTth in the ATP as well as in the ADP.Pi-state, peptide is bound
      and released within seconds. No correlation between ATP-binding or hydrolysis by
      DnaKTth and changes in the sigma32 peptide exchange rates could be detected. It
      thus appears that the DnaK system from Th. thermophilus has a different mechanism
      of coupling the nucleotide state to the fast and slow peptide exchange
      properties.

PMID- 9642066
TI  - Purified lens major intrinsic protein (MIP) forms highly ordered tetragonal two
      dimensional arrays by reconstitution.
AB  - Lens major intrinsic protein (MIP) is the founding member of the MIP family of
      membrane channel proteins. Its isolation from ovine lens fibre cell membranes and
      its two-dimensional crystallization are described. Membranes were solubilized
      with N-octyl-beta-D-glucoside and proteins fractionated by sucrose gradient
      centrifugation containing decyl-beta-D-maltoside. MIP was purified by cation
      exchange chromatography, and homogeneity was assessed by mass analysis in the
      scanning transmission electron microscope. Purified MIP reconstituted into a
      lipid bilayer at a low lipid-to-protein ratio formed highly ordered tetragonal
      two-dimensional crystals. The square unit cell had a side length of 6.4 nm, and
      exhibited in negative stain four stain-excluding elongated domains surrounding a
      central stain-filled depression. Projection maps of freeze-dried crystals
      exhibited a resolution of 9 A, and revealed a monomer structure of MIP consisting
      of distinct densities. Despite significant differences in the packing of
      tetramers in the crystals, the projection map of the MIP monomer was similar to
      that of aquaporin-1 (AQP1), the first member of the MIP family which had its
      structure resolved to 6 A. Our protocols for the purification and reconstitution
      of MIP establish the feasibility for future work to visualize structure elements
      which determine the diverse functional properties of the MIP family members.

PMID- 9642067
TI  - Role of the C-terminal tryptophan residue for the structure-function of the
      alphavirus capsid protein.
AB  - The Semliki Forest virus capsid protein is a multifunctional protein which
      packages genomic RNA into nucleocapsid structures and binds to viral spike
      protein during budding. In addition, the capsid protein has an autoproteolytic
      activity whereby the C-terminal tryptophan is used as the substrate for
      cotranslational cleavage of the viral structure polyprotein. The autoproteolytic
      domain of the capsid protein has a chymotrypsin-like fold but has two additional
      short beta-strands which place the tryptophan into the active site. Here, we have
      substituted the C-terminal tryptophan of Semliki Forest virus capsid protein for
      alanine, arginine and phenylalanine and analysed the effects on different
      functions of the C protein such as nucleocapsid formation, spike binding and
      autoproteolytic activity. We found that (i) tryptophan is a better substrate for
      the autoproteolytic activity, (ii) the wild-type tryptophan is the only residue
      that allows efficient viral growth and (iii) an aromatic residue is important for
      correct initial folding and stability of the protein.

PMID- 9642068
TI  - Ribosomal proteins S5 and L6: high-resolution crystal structures and roles in
      protein synthesis and antibiotic resistance.
AB  - Antibiotic resistance is rapidly becoming a major medical problem. Many
      antibiotics are directed against bacterial ribosomes, and mutations within both
      the RNA and protein components can render them ineffective. It is well known that
      the majority of these antibiotics act by binding to the ribosomal RNA, and it is
      of interest to understand how mutations in the ribosomal proteins can produce
      resistance. Translational accuracy is one important target of antibiotics, and a
      number of ribosomal protein mutations in Escherichia coli are known to modulate
      the proofreading mechanism of the ribosome. Here we describe the high-resolution
      structures of two such ribosomal proteins and characterize these mutations. The
      S5 protein, from the small ribosomal unit, is associated with two types of
      mutations: those that reduce translational fidelity and others that produce
      resistance to the antibiotic spectinomycin. The L6 protein, from the large
      subunit, has mutations that cause resistance to several aminoglycoside
      antibiotics, notably gentamicin. In both proteins, the mutations occur within
      their putative RNA-binding sites. The L6 mutations are particularly drastic
      because they result in large deletions of an RNA-binding region. These results
      support the hypothesis that the mutations create local distortions of the
      catalytic RNA component.When combined with a variety of structural and
      biochemical data, these mutations also become important probes of the
      architecture and function of the translational machinery. We propose that the C
      terminal half of S5, which contains the accuracy mutations, organizes RNA
      structures associated with the decoding region, and the N-terminal half, which
      contains the spectinomycin-resistance mutations, directly interacts with an RNA
      helix that binds this antibiotic. As regards L6, we suggest that the mutations
      indirectly affect proofreading by locally distorting the EF-Tu.GTP.aminoacyl tRNA
      binding site on the large subunit.

PMID- 9642069
TI  - Structural investigation of the cofactor-free chloroperoxidases.
AB  - The structures of cofactor-free haloperoxidases from Streptomyces aureofaciens,
      Streptomyces lividans, and Pseudomonas fluorescens have been determined at
      resolutions between 1.9 A and 1.5 A. The structures of two enzymes complexed with
      benzoate or propionate identify the binding site for the organic acids which are
      required for the haloperoxidase activity. Based on these complexes and on the
      structure of an inactive variant, a reaction mechanism is proposed for the
      halogenation reaction with peroxoacid and hypohalous acid as reaction
      intermediates. Comparison of the structures suggests that a specific halide
      binding site is absent in the enzymes but that hydrophobic organic compounds may
      fit into the active site pocket for halogenation at preferential sites.

PMID- 9642070
TI  - Three-dimensional structures of single-chain Fv-neuraminidase complexes.
AB  - The structure of the complex between a recombinant single-chain Fv construct of
      antibody NC10 with a five-residue peptide linker between VH and VL (termed
      scFv(5)), and its antigen, tetrameric neuraminidase from influenza virus (NA),
      has been determined and refined at 2.5 A resolution. The antibody-antigen binding
      interface is very similar to that of a similar NC10 scFv-NA complex in which the
      scFv has a 15-residue peptide linker (scFv(15)), and the NC10 Fab-NA complex.
      However, scFv(5) and scFv(15) have different stoichiometries in solution. While
      scFv(15) is predominantly monomeric in solution, scFv(5) forms dimers
      exclusively, because the five-residue linker is not long enough to permit VH and
      VL domains from the same polypeptide associating and forming an antigen-binding
      site. Upon forming a complex with NA, scFv(15) forms a approximately 300 kDa
      complex corresponding to one NA tetramer binding four scFv(15) monomers, while
      scFv(5) forms a approximately 590 kDa complex, corresponding to two NA tetramers
      crosslinked by four bivalent scFv(5) dimers. However, the dimeric scFv(5) in the
      scFv(5)-NA crystals does not crosslink NA tetramers, and modelling studies
      indicate that it is not possible to pack four dimeric and simultaneously bivalent
      scFvs between the NA tetramers with only a five-residue linker between VH and VL.
      The inability arises from the exacting requirement to orient the two antigen
      binding surfaces to bind the tetrameric NA antigen while avoiding steric clashes
      with NC10 scFv(5) dimers bound to other sites on the NA tetramer. The utility of
      bivalent or bifunctional scFvs with short linkers may therefore be restricted by
      the steric constraints imposed by binding multivalent antigens.

PMID- 9642071
TI  - Solution structure and dynamics of the bioactive retroviral M domain from Rous
      sarcoma virus.
AB  - A biologically active construct of the retroviral M domain from the avian Rous
      sarcoma virus is defined and its solution structure described. This M domain is
      fully active in budding and infectivity without myristylation. In spite of a
      sequence homology level that suggests no relationship among M domains and the
      family of matrix proteins in mammalian retroviruses, the conserved structural
      elements of a central core allow an M domain sequence motif to be described for
      all retroviruses. The surface of the M domain has a highly clustered positive
      patch comprised of sequentially distant residues. An analysis of the backbone
      dynamics, incorporating rotational anisotropy, is used to estimate the
      thermodynamics of proposed domain oligomerization.

PMID- 9642072
TI  - A disorder-to-order transition coupled to DNA binding in the essential zinc
      finger DNA-binding domain of yeast ADR1.
AB  - The motional dynamics and solvent-exchange behavior of free and DNA-bound forms
      of the minimal zinc-finger DNA-binding domain of the yeast transcription factor
      ADR1 (ADR1-DBD) are investigated using NMR. The parameters measured include the
      1H-15N heteronuclear NOE, 15N and 1H T1 relaxation rates, 15N T2 relaxation
      rates, and solvent-exchange rates. The spin relaxation parameters, spectral
      density maps, and solvent-exchange behavior show that, exclusive of the N and C
      termini, three distinct regions of free ADR1-DBD exhibit different motions on
      multiple timescales. The N-terminal proximal, or accessory, region appears to be
      unstructured and highly flexible: it exhibits large amplitude motions on a
      picosecond timescale, little or no protection from solvent exchange, and random
      coil proton chemical shifts. The two zinc fingers tumble anisotropically as
      folded domains, with the tumbling of the individual fingers being only partly
      correlated to each other, and are modestly protected from solvent exchange except
      near the tips of the fingers and in the linker joining them. Free ADR1-DBD
      exhibits exchange broadening around P97 in the proximal region, at the tip of
      finger 1, and throughout finger 2. Upon binding, most of the proximal region and
      both zinc fingers tumble as a single domain and exhibit significantly reduced
      picosecond timescale motions. This region becomes more protected from solvent
      exchange. The bound portion of the proximal region is proposed to lie exposed on
      the surface of the DNA. Exchange broadening remains around P97 but also becomes
      evident for residues in direct contact with the DNA and in the linker. We
      conclude that the region of ADR1-DBD essential for high-affinity binding
      undergoes a disorder-to-order transition upon binding to its cognate DNA and,
      together with the zinc fingers, forms a cohesive molecular complex with the
      nucleic acid.

PMID- 9642073
TI  - Ecotin: a serine protease inhibitor with two distinct and interacting binding
      sites.
AB  - The interaction between ecotin and target proteases with trypsin-like specificity
      has been systematically dissected to understand the structural basis of ecotin's
      broad inhibitory specificity and the role of the secondary binding site. Site
      directed and region-specific mutagenesis were preformed at ecotin's primary site
      P1 residue (84), the C-terminal dimer interface (133 to 142), and two surface
      loops of the secondary binding site (67 to 70, 108 to 113). Substitutions at the
      P1 position resulted in less than fivefold difference in the potency of ecotin
      binding to rat trypsin, suggesting that the extended binding site is important in
      binding. A ten amino acid C-terminal truncation variant showed threefold weaker
      self-association but remained a dimer. The interactions of the secondary binding
      site of ecotin with bovine trypsin, rat trypsin and human urokinase-type
      plasminogen activator (uPA) were investigated with alanine substitutions in
      ecotin at Trp67, Gly68, Tyr69, Asp70, Arg108, Asn110, Lys112 and Leu113, which
      formed contacts between the inhibitor and protease. By combining these mutations
      at the secondary binding site with mutations in the primary binding site the
      molecular recognition between ecotin and its target serine proteases was probed.
      The contrast in the Ki values of the various ecotin variants towards bovine
      trypsin, rat trypsin and human uPA established the role of ecotin's secondary
      binding site in recognizing these homologous serine proteases. Ecotin binds to
      proteases with a chymotrypsin fold through a combination of primary and secondary
      site surface loops and is amenable to redesign of its potency and specificity for
      this class of enzymes.

PMID- 9642074
TI  - Inter-helical interactions in the leucine zipper coiled coil dimer: pH and salt
      dependence of coupling energy between charged amino acids.
AB  - We have investigated the physical nature of the observed coupling energy (Delta
      Delta DeltaGint) between the charged side-chains of the three inter-helical g<-
      >e' (i, i'+5) pairs (E<-->R, E<-->K, and E<-->E) in the leucine zipper coiled
      coil dimer. Circular dichroism (CD) spectroscopy measured the thermal stability
      of eight proteins derived from the basic region leucine zipper domain of chicken
      VBP, the mammalian TEF at seven pHs and three KCl concentrations. Data from these
      proteins were used to construct double mutant alanine thermodynamic cycles and
      determine coupling energies (Delta Delta DeltaGint) for the three g<-->e' pairs.
      The attractive E<-->R coupling energy of -0.6 kcal mol-1 at low salt decreases to
      -0.2 kcal mol-1 at high salt. The E<-->K coupling energy of -0.5 kcal mol-1 at
      low salt decreases to -0.1 kcal mol-1 at high salt. The repulsive E<-->E coupling
      energy of +0.8 kcal mol-1 at low salt drops to +0.4 at high salt. Reducing the pH
      to 2.2 halved the attractive coupling energy for the E<-->R and E<-->K pairs
      while abolishing the repulsion of the E<-->E pair. 13C NMR of a protein
      selectively labeled with [13Cdelta]glutamate that contained three E<-->R and one
      R<-->E pair identified four glutamates shifted upfield. We suggest that this is
      due to electronic perturbation of glutamates in inter-helical E<-->R
      interactions. Taken together, these data indicate that the E<-->R coupling energy
      of -0.5 kcal mol-1 at pH 7.4 and 150 mM KCl has an electrostatic component.

PMID- 9642075
TI  - Design, synthesis and structure of a zinc finger with an artificial beta-turn.
AB  - We have incorporated a bicyclic beta-turn mimetic (BTD; beta-turn dipeptide) into
      a zinc finger, creating a zinc finger with an artificial beta-turn. The designed
      peptide chelates zinc and has the same fold as the unmodified native zinc finger
      (finger 3 of the human YY1 protein). A combination of 1H NMR and structure
      calculations reveals that, in solution, this zinc finger has a fold similar to
      the known wild-type crystal structure and to other zinc fingers containing the
      consensus sequence X3-Cys-X4-Cys-X12-His-X3-His-X. The peptide was designed with
      BTD between the chelating cysteine residues, with BTD forming a type II' beta
      turn linking the two strands of a distorted anti-parallel beta-sheet. The C
      terminal portion of the peptide forms a helix with zinc co-ordinating histidine
      residues on successive turns of the helix. This work represents a step towards
      developing methods by which parts of a target protein may be replaced by peptide
      mimetics.

PMID- 9642076
TI  - Dimer-to-tetramer transformation: loop excision dramatically alters structure and
      stability of the ROP four alpha-helix bundle protein.
AB  - The ROP loop excision mutant RM6 shows dramatic changes in structure and
      stability in comparison to the wild-type protein. Removal of the five amino acids
      (Asp30, Ala31, Asp32, Glu33, Gln34) from the loop results in a complete
      reorganization of the protein as evidenced by single crystal X-ray analysis and
      thermodynamic unfolding studies. The homodimeric four-alpha-helix motif of the
      wild-type structure is given up. Instead a homotetrameric four-alpha-helix
      structure with extended, loop-free helical monomers is formed. This intriguing
      structural change is associated with the acquisition of hyperthermophilic
      stability. This is evident in the shift in transition temperature from 71
      degreesC characteristic of the wild-type protein to 101 degreesC for RM6.
      Accordingly the Gibbs energy of unfolding is increased from 71.7 kJ (mol of
      dimer)-1 to 195.1 kJ (mol of tetramer)-1. The tetramer-to-monomer transition
      proceeds highly cooperatively involving an enthalpy change of DeltaH=1073+/-30 kJ
      (mol of tetramer)-1 and a heat capacity change at the transition temperature of
      DeltaDNCp=14.9(+/-)3% kJ (mol of tetramerxK)-1. The two-state nature of the
      unfolding reaction is reflected in coinciding calorimetric and van't Hoff
      enthalpy values.

PMID- 9642077
TI  - Engineering bidentate macromolecular inhibitors for trypsin and urokinase-type
      plasminogen activator.
AB  - Ecotin, a dimeric serine protease inhibitor from Escherichia coli, is a novel
      platform for inhibitor design. An approach using the three-dimensional structure
      of the ecotin-trypsin complex to guide combinatiorial design efforts was taken to
      create potent bidentate ecotin inhibitors for trypsin and human urokinase-type
      plasminogen activator (uPA). The ecotin surface loop that was redesigned is
      composed of residues 67 to 70 (60 s loop), and binds to the target protease at a
      region 25 A from the enzyme active site. Two ecotin phage display libraries were
      constructed to exploit the binding interactions at the 60 s loop. The ecotin 60X4
      library, in which residues 67 to 70 of ecotin were randomized, was panned against
      rat and bovine trypsin in parallel for four rounds. Panning against bovine
      trypsin resulted in enrichment of ecotin phage but did not yield a consensus
      sequence. Panning against rat trypsin resulted in enrichment as well as the
      ecotin consensus sequence WGFP at positions 67 to 70. The variant ecotin encoded
      by this sequence inhibited rat trypsin at 80 pM, a 12-fold improvement over
      ecotin wild-type (WT). A second generation library, ecotin M84R+60X4 including an
      additional methionine to arginine substitution at position 84 in the primary
      binding site of ecotin, was generated for panning against uPA and rat trypsin.
      Panning against rat trypsin resulted in enrichment but no consensus sequence.
      Panning against uPA resulted in enrichment as well as the different ecotin
      consensus sequence WGYR at positions 67 to 70. Ecotin M84R+D70R bound to uPA at
      50 pM, a 56,000-fold increase in binding compared to ecotin WT. Furthermore,
      ecotin M84R+D70R achieved a 13,680-fold preference of specificity towards uPA
      versus rat trypsin. The fact that the 60 s loop of ecotin plays different roles
      in binding to trypsin and uPA suggests this site can be used to introduce
      specificity and potency for other members of the serine proteases with a
      chymotrypsin fold.

PMID- 9642079
TI  - Apologia 

PMID- 9642078
TI  - Structural basis for the high affinity of amino-aromatic SH2 phosphopeptide
      ligands.
AB  - An anthranyl moiety placed at the N terminus of a phosphotyrosine peptide
      potentiates the inhibitory effect of this small peptide on the binding of the
      Grb2 SH2 domain to the EGF receptor. Using molecular modeling procedures based on
      the Lck SH2 domain structure, this observation was rationalized in terms of a
      suitably favorable pi-pi stacking interaction between the anthranyl moiety and
      the arginine alphaA2 (ArgalphaA2) residue side-chain of Grb2 SH2. The crystal
      structure of the Grb2 SH2 domain in complex with the inhibitor 2-Abz-EpYINQ-NH2
      (IC50 26 nM) has been solved in two different crystal forms at 2.1 and 1.8 A
      resolution. This structure confirms the modeling based on the Lck SH2 domain. The
      ArgalphaA2 residue is conserved in most SH2 domains. Thus, as expected, the
      anthranyl group also confers high affinity to small peptide ligands of other SH2
      domains such as Lck-, PLC-gamma-amino-terminal and p85 amino-terminal SH2 domains
      as demonstrated by structure affinity relationships (SAR) data. These potent
      peptides with an amino-terminal surrogate group and the structure of Grb2 SH2
      domain in complex with one such peptide represent good starting points for the
      design and optimization of new inhibitors of many SH2 domains.

PMID- 9642080
TI  - Corrigendum 

PMID- 9642081
TI  - DNA microloops and microdomains: a general mechanism for transcription activation
      by torsional transmission.
AB  - Prokaryotic transcriptional activation often involves the formation of DNA
      microloops upstream of the polymerase binding site. There is substantial evidence
      that these microloops function to bring activator and polymerase into close
      spatial proximity. However additional functions are suggested by the ability of
      certain activators, of which FIS is the best characterised example, to facilitate
      polymerase binding, promoter opening and polymerase escape. We review here the
      evidence for the concept that the topology of the microloop formed by such
      activators is tightly coupled to the structural transitions in DNA mediated by
      RNA polymerase. In this process, which we term torsional transmission, a major
      function of the activator is to act as a local topological homeostat. We argue
      that the same mechanism may also be employed in site-specific DNA inversion.

PMID- 9642082
TI  - Tyrosine phosphorylation in Escherichia coli.
AB  - The phosphorylation on tyrosine of a protein in Escherichia coli both in vivo and
      in vitro was revealed by recognition by anti-phosphotyrosine antibodies,
      labelling with [gamma-32P]ATP, and phosphoamino acid analysis. This protein,
      which we name TypA, is the product of the o591 reading frame as revealed by N
      terminal sequencing and antibody cross-reactivity. Inactivation of typA altered
      the patterns of protein synthesis during both exponential growth and carbon
      starvation. These alterations included the disappearance of an acidic isoform of
      both the universal stress protein UspA and carbon starvation protein Csp15, and
      increased synthesis of the histone-like protein H-NS. The sequence of TypA from
      strain K-12 differs from that of an enteropathogenic strain in six amino acid
      residues and the protein is three residues shorter. We propose that TypA
      interacts with global regulatory networks and that its phosphorylation may be
      relevant to pathogenesis.

PMID- 9642083
TI  - Unusual domain pairing in a mutant of bovine lens gammaB-crystallin.
AB  - beta gamma-Crystallins from the eye lens are proteins consisting of two domains
      joined by a short linker. All 3D structures solved so far reveal a similar pseudo
      2-fold pairing of the domains, reflecting their presumed ancient origin from a
      single-domain homodimer. Here we report the 2.2 A X-ray structure of the N
      terminal domain of gammaB-crystallin, bearing a mutation of a residue involved in
      domain contacts in the native molecule (Phe56Ala). It forms a crystallographic
      homodimer, yet the domain orientation is different from native beta gamma
      crystallins. It is considered that the new orientation derives from two
      structural features. (1) The replacement of the bulky phenylalanine 56 by an
      alanine results in a different optimal hydrophobic packing of interface residues
      between identical domains. (2) The paired domains have extensions derived from
      the domain linker, each containing a proline conserved in gamma-crystallins, and
      the resulting steric constraints preclude a native-like pairing but support the
      new arrangement. These data highlight the pivotal role of interface residues and
      sequence extensions in overall domain assembly.

PMID- 9642084
TI  - Reconstitution of the degradation of the mRNA for ribosomal protein S20 with
      purified enzymes.
AB  - Previous work has implicated poly(A) polymerase I (PAP I), encoded by the pcnB
      gene, in the decay of a number of RNAs from Escherichia coli. We show here that
      PAP I does not promote the initiation of decay of the rpsT mRNA encoding
      ribosomal protein S20 in vivo; however, it does facilitate the degradation of
      highly folded degradative intermediates by polynucleotide phosphorylase. As
      expected, purified degradosomes, a multi-protein complex containing, among
      others, RNase E, PNPase, and RhlB, generate an authentic 147-residue RNase E
      cleavage product from the rpsT mRNA in vitro. However, degradosomes are unable to
      degrade the 147-residue fragment in the presence of ATP even when it is
      oligoadenylated. Rather, both continuous cycles of polyadenylation and PNPase
      activity are necessary and sufficient for the complete decay of the 147-residue
      fragment in a process which can be antagonized by the action of RNase II.
      Moreover, both ATP and a non-hydrolyzable analog, ATPgammaS, support the PAP I
      and PNPase-dependent degradation of the 147-residue intermediate implying that
      ATPase activity, such as that which may reside in RhlB, a putative RNA helicase,
      is not necessarily required. Alternatively, the rpsT mRNA can be degraded in
      vitro by a second 3'-decay pathway which is dependent on PAP I, PNPase and ATP
      alone. Our results demonstrate that a hierarchy of RNA secondary structures
      controls access to exonucleolytic attack on 3' termini. Moreover, decay of a
      model mRNA can be reconstituted in vitro by a small number of purified components
      in a process which is more dynamic and ATP-dependent than previously imagined.

PMID- 9642085
TI  - Cooperative interaction between the DNA-binding domains of PU.1 and IRF4.
AB  - The two lymphoid-specific transcription factors PU.1 and IRF4 form a cooperative
      ternary complex at immunoglobulin enhancer elements such as the lambdaB and
      kappaE3' sites. We report here that the synergy of this interaction can be
      reconstituted in part with the DNA-binding domains of the two proteins. The
      minimal DNA binding-domain of IRF4 was mapped to residues 20 to 137,
      corresponding to the conserved DNA-binding region of other interferon regulatory
      factors (IRFs). This domain can bind weakly to a synthetic murine lambdaB
      element, while IRF4 constructs that contain residues 1 to 19 require the presence
      of PU.1 for DNA-binding at similar concentrations. Fluorescence polarization of
      fluorescein-labelled DNA was used to show that the presence of residues 1 to 19
      decreases the binding affinity of IRF4 N-terminal constructs from two- to
      fivefold. However, all constructs bound better to the lambdaB element in the
      presence of the DNA-binding domain of PU.1. This cooperative interaction was not
      dependent on phosphorylation of the PEST domain of PU.1, but was dependent on the
      proper spacing of the binding sites for PU.1 and IRF4. These data suggest that at
      least part of the cooperative interaction between full-length PU.1 and IRF4
      involves the DNA-binding domains of the two proteins. NMR spectroscopy of 15N
      labelled PU.1 and IRF4 constructs indicates that the PEST domain of PU.1 and
      residues 1 to 19 of IRF4 may be unstructured in the isolated proteins.

PMID- 9642086
TI  - An Arg/Lys-rich core peptide mimics TRBP binding to the HIV-1 TAR RNA upper
      stem/loop.
AB  - TRBP is a cellular protein that binds to the HIV-1 leader RNA, TAR. Circular
      dichroism experiments have shown that a 24 amino acid peptide (TR1), located
      within a dsRNA binding domain (dsRBD) of TRBP, binds TAR with a 3:1
      stoichiometry, eliciting a conformational change involving base unstacking. The
      binding characteristics of synthetic structural variants of TAR indicate that
      guanine residues play a key role in the TR1-RNA interaction and that binding
      sites exist in the upper-stem/loop and lower stem region of TAR. Deletion
      analysis of TR1 has led to the identification of a 15 amino acid subpeptide
      (TR13) which is necessary and sufficient to bind to the high affinity upper
      stem/loop binding site of TAR. Alanine scanning of TR13 has revealed that
      mutations in either Lys or Arg residues result in altered TAR-binding, and
      molecular modelling/docking experiments have shown that the two Arg residues of
      TR13 can interact with two appropriately spaced guanine residues in the upper
      stem/loop of TAR. The TR13 lysine residues appear to be essential for maintaining
      structural integrity and the correct positioning of the Arg side-chains. We
      propose that TRBP binds TAR by means of a "2-G hook" motif and that the binding
      specificity of this particular member of the family of double-stranded RNA
      binding proteins lies within the highly conserved dsRBD core motif. Finally, our
      results also suggest that TRBP may function in vivo by modifying the tertiary
      structure of TAR RNA.

PMID- 9642087
TI  - Expansion of CTG repeats from human disease genes is dependent upon replication
      mechanisms in Escherichia coli: the effect of long patch mismatch repair
      revisited.
AB  - Many human hereditary disease genes have been recently associated with the
      expansion of CTG/GAC repeats. We have used a plasmid-based assay in Escherichia
      coli to investigate the instability of a (CTG/GAC) insert containing 64 repeats.
      Using this assay, expansions were biochemically detected and subsequently
      quantified. We show that the occurence of expansions within these trinucleotide
      repeats is dependent upon replicative mechanisms. Expansions of up to 30 repeats
      and deletions of almost all possible sizes occured regardless of the orientation
      of the insert relative to the replication origin. In contradiction to a previous
      report, the mismatch repair pathway was found to strongly stabilize these repeat
      stretches.

PMID- 9642088
TI  - Hepatitis B virus capsid: localization of the putative immunodominant loop
      (residues 78 to 83) on the capsid surface, and implications for the distinction
      between c and e-antigens.
AB  - Hepatitis B virus capsid protein comprises a 149 residue "assembly" domain that
      polymerizes into icosahedral particles, and a 34 residue RNA-binding "protamine"
      domain. Recently, the capsid structure has been studied to resolutions below 10 A
      by cryo-electron microscopy, revealing much of its alpha-helical substructure and
      that it appears to have a novel fold for a capsid protein; however, the
      resolution is still too low for chain-tracing by conventional criteria. Aiming to
      establish a fiducial marker to aid in the process of chain-tracing, we have used
      cryo-microscopy to pinpoint the binding site of a monoclonal antibody that
      recognizes the peptide from residues 78 to 83. This epitope resides on the outer
      rim of the 30 A long spikes that protrude from the capsid shell. These spikes are
      four-helix bundles formed by the pairing of helix-turn-helix motifs from two
      subunits; by means of a tilting experiment, we have determined that this bundle
      is right-handed. Variants of the same protein present two clinically important
      and non-crossreactive antigens: core antigen (HBcAg), which appears early in
      infection as assembled capsids; and the sentinel e-antigen (HBeAg), a non
      particulate form. Knowledge of the binding site of our anti-HBcAg antibody bears
      on the molecular basis of the distinction between the two antigens, which appears
      to reflect conformational differences between the assembled and unassembled
      states of the capsid protein dimer, in addition to epitope masking in capsids.

PMID- 9642089
TI  - On the potential role of the amino nitrogen atom as a hydrogen bond acceptor in
      macromolecules.
AB  - Crystallographic studies of duplex DNA have indicated that opposing exocyclic
      amino groups may form close NH&ctdot;:N contacts. To study the nature of such
      interactions, we have examined the database of small molecule, high-resolution
      crystal structures for more accurate examples of this type of unconventional
      interaction. We have found cases where the amino groups in guanine and adenine
      bases accept hydrogen bonds from conventional donors, such as amino or hydroxyl
      groups. More frequently, the purine amino group was found to contact closely
      electropositive C-H groups. Searches of the nucleic acid structural databases
      also yielded several examples where the purine amino group is contacted by
      hydrogen bond donors in macromolecules. Ab initio calculations indicate that the
      hydrogen-amino contact is improved energetically when the amino group moves from
      the conventional geometry, where all atoms are co-planar with the base, to one in
      which the hydrogen atoms lie out of the plane and the nitrogen is at the apex of
      a pyramid, resulting in polarization of the amino group. The combined structural
      and theoretical data suggest that the amino group is flexible, and can
      accommodate close contacts, because the resulting polarization permits
      electropositive atoms to approach the amino group nitrogen more closely than
      expected for their conventional van der Waals radii. The flexibility of the amino
      group may permit particular DNA conformations that enforce hydrogen-amino
      contacts to optimize favorable stacking interactions, and it may play a role in
      the recognition of nucleosides. We speculate that the amino group can accept
      hydrogen bonds under special circumstances in macromolecules, and that this
      ability might play a mechanistic role in catalytic processes such as deamination
      or amino transfer.

PMID- 9642090
TI  - A bisubstrate analog induces unexpected conformational changes in
      phosphoglycerate kinase from Trypanosoma brucei.
AB  - The glycolytic enzyme phosphoglycerate kinase (PGK) catalyzes phosphoryl transfer
      between 1,3-bis-phosphoglycerate and ADP to form 3-phosphoglycerate and ATP.
      During catalysis, a major hinge bending motion occurs which brings the N and C
      terminal enzyme domains and their bound substrates together and in-line for
      phosphoryl transfer. We have crystallized Trypanosoma brucei PGK in the presence
      of the bisubstrate analog, adenylyl 1,1,5,5-tetrafluoropentane-1, 5
      bisphosphonate, and solved the structure of this complex in two different crystal
      forms at 1.6 and 2.0 A resolution, obtained from PEG 8000 and ammonium phosphate
      solutions, respectively. These high resolution structures of PGK:inhibitor
      complexes are of particular interest for drug design since Trypanosoma brucei,
      the causative agent of African sleeping sickness, relies on glycolysis as its
      sole energy source. In both structures, the inhibitor is bound in a fully
      extended conformation with its adenosine moiety assuming exactly the same
      position as in ADP:PGK complexes and with its 5' phosphonate group occupying part
      of the 1,3-bis-phosphoglycerate binding site. The bisubstrate analog forces PGK
      to assume a novel, "inhibited" conformation, intermediate in hinge angle between
      the native structures of open and closed form PGK. These structures of enzyme
      inhibitor complexes demonstrate that PGK has two distinct hinge points that can
      each be independently activated. In the "PEG" structure, the C-terminal hinge is
      partially activated while the N-terminal hinge point remains in an open state. In
      the "phosphate" structure, closure of the N-terminal hinge point is also evident.
      Finally and most unexpectedly, both complex structures also contain a 3 A shift
      of a helix that lies outside the flexible hinge region. We propose that a
      transient shift of this helix is a required element of PGK hinge closure during
      catalysis.

PMID- 9642091
TI  - Backbone dynamics of the EGF-like domain of heregulin-alpha.
AB  - The backbone dynamics of the 63 residue epidermal growth factor (EGF)-like domain
      of heregulin-alpha (HRG-alpha) have been characterized by measurement of
      longitudinal relaxation rate constants (R1), transverse relaxation rate constants
      (R2), and steady-state ?1H?-15N nuclear Overhauser effects for the 15N nuclear
      spins using proton-detected heteronuclear NMR spectroscopy. Analysis of the R2/R1
      ratios in conjunction with the known structure of the HRG-alpha EGF-like domain
      yields a rotational correlation time of approximately 8.4 ns, suggesting that the
      protein aggregates under the solution conditions used (3.8 mM protein, 50 mM
      sodium acetate, pH 4.5, 20 degreesC), and that it tumbles with an axially
      symmetric diffusion tensor (D parallel/D perpendicular=1.4). Sedimentation
      equilibrium experiments confirm that the EGF-like domain of HRG-alpha undergoes
      weak self-association under these conditions and are consistent with a simple
      monomer-dimer equilibrium with a dimer-dissociation constant Kd=1.6(+/-0.4) mM.
      The relaxation data were analyzed using a reduced spectral density mapping
      approach to avoid systematic effects of aggregation on the usual model-free
      formalism. The reduced spectral densities show that residues near the N terminus
      (residues 3 to 5 and 7 to 12), in the Omega-loop between beta-strands 2 and 3
      (residues 24 to 31), and in particular the C-terminal 13 residues (residues 51 to
      63), have significant mobility on a picosecond/nanosecond time-scale. In
      addition, conformational exchange on a microsecond time-scale was identified for
      residues 44 to 46 on the basis of observed differences in R2 at 11.7 and 14.1 T.
      The mobility identified near the N terminus and in the vicinity of residues 44 to
      46 may be important in allowing the interactions of heregulin with multiple
      receptors.

PMID- 9642092
TI  - Exploring the folding pathways of annexin I, a multidomain protein. I. non-native
      structures stabilize the partially folded state of the isolated domain 2 of
      annexin I.
AB  - Proteins of the annexin family constitute very attractive models because of their
      four approximately 70 residue domains, D1 to D4, exhibiting an identical topology
      comprising five helix segments with only a limited sequence homology of
      approximately 30%. We focus on the isolated D2 domain, which is only partially
      folded. A detailed analysis of this equilibrium partially folded state in aqueous
      solution and micellar solution using 15N-1H multidimensional NMR is presented.
      Comparison of the residual structure of the entire domain with that of shorter
      fragments indicates the presence of long-range transient hydrophobic interactions
      that slightly stabilize the secondary structure elements. The unfolded domain
      tends to behave as a four-helix, rather than as a five-helix domain. The ensemble
      of residual structures comprises: (i) a set of native structures consisting of
      three regions with large helix populations, in rather sharp correspondence with
      A, B and E helices, and a small helix population in the second part of the C
      helix; (ii) a set of non-native local structures corresponding to turn-like
      structures stabilized by several side-chain to side-chain interactions and helix
      disruptive side-chains to backbone interactions. Remarkably, residues involved in
      these local non-native interactions are also involved, in the native structure,
      in structurally important non-local interactions. During the folding process of
      annexin I, the local non-native interactions have to switch to native long-range
      interactions. This structural switch reveals the existence of a sequence-encoded
      regulation of the folding pathways and kinetics, and emphasizes the key role of
      the non-native local structures in this regulation.

PMID- 9642093
TI  - Exploring the folding pathways of annexin I, a multidomain protein. II. Hierarchy
      in domain folding propensities may govern the folding process.
AB  - In the context of exploring the relationship between sequence and folding
      pathways, the multi-domain proteins of the annexin family constitute very
      attractive models. They are constituted of four approximately 70-residue domains,
      named D1 to D4, with identical topologies but only limited sequence homology of
      approximately 30%. The domains are organized in a pseudochiral circular
      arrangement. Here, we report on the folding propensity of the D1 domain of
      annexin I obtained from overexpression in Escherichia coli. Unlike the D2 domain,
      which is only partially folded, the isolated D1 domain exhibits autonomous
      refolding in pure aqueous solution. Similarly, the D3 domain and D2-D3 module
      were obtained from expression in E. coli but were found to be largely unfolded.
      No conclusion could be drawn for the D4 domain because it was not possible to
      extract it from the bacterial inclusion bodies. The data allow us to propose a
      plausible scenario for the annexin I folding. This working model states that
      firstly the D1 domain folds, and the D2 and D3 domains remain partly unfolded,
      facilitating the docking of the D4 domain to the D1 domain. In a second step, the
      D1 and D4 domains dock, and D4 may fold if already not folded. The final step
      starts with the stabilization of the D1-D4 module. This stabilization is crucial
      for allowing the non-native local interactions inside the still partially
      unfolded D2 domain to switch to the native long-range interactions involving D4.
      This switch allows the complete folding of D2 and D3. The model proposes a
      sequential and hierarchical process for the folding of annexin I and emphasizes
      the role of both native framework and non-native structures in the process.

PMID- 9642094
TI  - Conformational constraints for protein self-cleavage in the proteasome.
AB  - The proteasome is the central enzyme of protein degradation in the cytosol and
      the nucleus. It is involved in the removal of abnormal, misfolded or incorrectly
      assembled proteins, in the processing or degradation of transcriptional
      regulators in stress response, in degradation of cyclins in cell-cycle control,
      in the destruction of transcription factors or metabolic enzymes in cell
      differentiation and metabolic response, and in MHC class I mediated cellular
      immune response. By the analysis of the crystal and molecular structures of the
      20 S proteasomes from the archaeon Thermoplasma acidophilum and from yeast it was
      shown that the beta-type subunits in which the proteolytic activities reside are
      members of the N-terminal nucleophile (Ntn) protein family. They are synthesized
      as proproteins and become active by autoprocessing at a Gly-1-Thr1 bond. The
      Thr1Ala mutant of subunit beta1/Pre3 of the 20 S proteasome from yeast is unable
      to autolyse. Its crystal and molecular structure at 2.2 A resolution described
      here shows that the pro-segment adopts a well-defined gamma-turn conformation at
      Gly-1 and provides a first view at an autolysis site in Ntn hydrolases. The Gly-1
      carbonyl oxygen displays two hydrogen bonds. The modelled Thr1 side-chain is
      located above the gamma-turn bulge such that addition of its nucleophilic
      hydroxyl group to the electrophilic Gly-1 carbonyl carbon atom may proceed by
      very small motions. The pro-segment binding site and the catalytic site provide a
      rigid structural framework and appropriate hydrogen bond donors for this
      reaction. The same structure also supports addition of the Thr1 hydroxyl group to
      the carbonyl carbon atom of Leu-2 as a model for the first step in substrate
      hydrolysis by the proteasome.

PMID- 9642095
TI  - Automated classification of antibody complementarity determining region 3 of the
      heavy chain (H3) loops into canonical forms and its application to protein
      structure prediction.
AB  - A computer-based algorithm was used to cluster the loops forming the
      complementarity determining region (CDR) 3 of the heavy chain (H3) into canonical
      classes. Previous analyses of the three-dimensional structures of CDR loops (also
      known as the hypervariable regions) within antibody immunoglobulin variable
      domains have shown that for five of the six CDRs there are only a few main-chain
      conformations (known as canonical forms) that show clear relationships between
      sequence and structure. However, the larger variation in length and conformation
      of loops within H3 has limited the classification of these loops into canonical
      forms. The clustering procedure presented here is based on aligning the
      Ramachandran-coded main-chain conformation of the residues using a dynamic
      algorithm that allows the insertion of gaps to obtain an optimum alignment. A
      total of 41 H3 loops out of 62 non-identical loops, extracted from the Brookhaven
      Protein Data Bank, have been automatically grouped into 22 clusters. Inspection
      of the clusters for consensus sequences or intra-loop interactions or invariant
      conformation led to the proposal of 13 canonical forms representing 31 loops.
      These canonical forms include a consideration of the geometry of both the take
      off region adjacent to the bracing beta-strands and the remaining loop apex.
      Subsequently a new set of 15 H3 loops not included in the initial analysis was
      considered. The clustering procedure was repeated and nine of these 15 loops
      could be assigned to original clusters, including seven to canonical forms. A
      sequence profile was generated for each canonical form from the original set of
      loops and matched against the sequences of the new H3 loops. For five out of the
      seven new H3 loops that were in a canonical form, the correct form was identified
      at first rank by this predictive scheme.

PMID- 9642096
TI  - Detection of protein three-dimensional side-chain patterns: new examples of
      convergent evolution.
AB  - Detection of recurring three-dimensional side-chain patterns is a potential means
      of inferring protein function. This paper presents a new method for detecting
      such patterns and discusses various implications. The method allows detection of
      side-chain patterns without any prior knowledge of function, requiring only
      protein structure data and associated multiple sequence alignments. A recursive,
      depth-first search algorithm finds all possible groups of identical amino acids
      common to two protein structures independent of sequence order. The search is
      highly constrained by distance constraints, and by ignoring amino acids unlikely
      to be involved in protein function. A weighted root-mean-square deviation (RMSD)
      between equivalenced groups of amino acids is used as a measure of similarity.
      The statistical significance of any RMSD is assigned by reference to a
      distribution fitted to simulated data. Searches with the Ser/His/Asp catalytic
      triad, a His/His porphyrin binding pattern, and the zinc-finger Cys/Cys/His/His
      pattern are performed to test the method on known examples. An all-against-all
      comparison of representatives from the structural classification of proteins
      (SCOP) is performed, revealing several new examples of evolutionary convergence
      to common patterns of side-chains within different tertiary folds and in
      different orders along the sequence. These include a di-zinc binding
      Asp/Asp/His/His/Ser pattern common to alkaline phosphatase/bacterial
      aminopeptidase, and an Asp/Glu/His/His/Asn/Asn pattern common to the active sites
      of DNase I and endocellulase E1. Implications for protein evolution, function
      prediction and the rational design of functional regulators are discussed.

PMID- 9642097
TI  - Frequency of the C282Y mutation of hemochromatosis in five French populations.
AB  - Hereditary hemochromatosis mutation 845A (C282Y) in the HFE gene was recently
      described, and the C282Y frequencies were reported for various world populations.
      The aim of this study was to determine the Y allele frequencies of the C282Y
      mutation for five French populations. The most elevated value (= 5.6%) was
      obtained for Bretons, in accordance to the hypothesis indicating a Celtic origin
      of the hereditary hemochromatosis mutation.

PMID- 9642098
TI  - An improved method for generating retroviral producer clones for vectors lacking
      a selectable marker gene.
AB  - Most retroviral vectors used in preclinical and clinical studies contain a
      selectable marker gene to facilitate the generation of producer clones. However,
      the expression of such genes in target cells is often undesirable since this may
      modify cellular phenotype and invoke a host immune response. Unfortunately, the
      efficient identification of high-titer producer clones for vectors lacking a
      selectable marker gene continues to be problematic and lacking for a standard
      methodology. Despite recent improvements in the screening techniques for
      identifying high-titer producer clones without the aid of a selectable marker, a
      solution to the fundamental problem of the very low frequency occurrence of high
      titer clones within the starting cell population has not emerged. We have
      developed a strategy which greatly increases the frequency of virus-producing
      clones, including those with high-titer, within the population of transduced
      cells to be screened. This approach relies on the use of high-titer vector
      preparations generated in 293T cells by co-transfection of retroviral packaging
      and vector plasmids. Viral preparations of a vector lacking a selectable marker
      were used to repeatedly transduce exponentially growing packaging cells at a high
      multiplicity of infection (MOI). Each cell in the resulting polyclonal population
      of producer cells contained multiple copies of the unrearranged vector genome.
      Greater than 95% of the clones derived from this population produced vector
      particles as judged by slot blot analysis of viral RNA from conditioned media.
      Numerous clones with estimated titers of 10(5)-10(6) were identified. These
      titers were confirmed using a standard vector genome transmission assay. This
      approach significantly enhances the ability, without large scale screening, to
      easily identify high-titer clones lacking a selectable marker and should
      facilitate the routine use of simplified gene marking and therapeutic vectors.

PMID- 9642099
TI  - DNA-protein interactions in the proximal zeta-globin promoter: identification of
      novel CCACCC- and CCAAT-binding proteins.
AB  - The human zeta-globin gene is expressed in a tissue- and developmental-specific
      pattern, with expression confined to primitive erythroid cells of the embryonic
      yolk sac blood islands. Transgenic mouse studies have shown that the proximal
      zeta-globin promoter contains sequences that contribute to the stage-specificity
      of expression, but no systematic functional studies of the cis elements in the
      proximal zeta-globin promoter have been reported. In this paper, we show that a
      number of conserved sequence elements in the zeta-globin promoter are important
      for promoter activity in transiently transfected K562 erythroleukemia cells,
      which constitutively express zeta-globin. These include a GATA site at -105, a
      CCACC site at -93, a CCAAT box at -65, and a TATA box at -29. A highly conserved
      CCTCC sequence at -78 is not important for zeta-globin promoter activity in this
      system. Mutations at these sites do not result in increased promoter activity in
      OCIM1 cells, an erythroid line that does not express zeta-globin, suggesting none
      of these sites is a developmental silencer. Electrophoretic mobility shift assays
      show that K562 and OCIM1 nuclear extracts contain DNA-binding activities that
      interact with the -105 GATA, -65 CCAAT, and -29 TATA sites. In addition K562
      cells, but not OCIM1 cells, have an activity that binds the -93 CCACC site. GATA
      1 interacts with the GATA site. The K562 CCACC-binding protein is distinct from
      Sp1, Sp2, Sp3, Sp4, EKLF, and BKLF. A specific -65 CCAAT-binding activity is
      present in K562 and OCIM1 nuclear extracts that is distinct from other CCAAT
      binding proteins including CBF/NF-Y, C/EBP, NF-1, and CP2. Thus, we have
      identified two novel factors that may contribute to the tissue or developmental
      stage-specific expression of zeta-globin.

PMID- 9642100
TI  - The human Nramp2 gene: characterization of the gene structure, alternative
      splicing, promoter region and polymorphisms.
AB  - Nramp2 is a gene encoding a transmembrane protein that is important in metal
      transport, in particular iron. Mutations in nramp2 have been shown to be
      associated with microcytic anemia in mk/mk mice and defective iron transport in
      Belgrade rats. Nramp2 contains a classical iron responsive element in the 3'
      untranslated region that confers iron dependent mRNA stabilization. In this
      report, we describe a splice variant form of human nramp2 that has the carboxyl
      terminal 18 amino acids substituted with 25 novel amino acids and has a new 3'
      untranslated region lacking a classical iron-responsive element. This splice form
      of nramp2, nramp2 non-IRE, was found to be derived from splicing of an additional
      exon into the terminal coding exon. The nramp2 gene is comprised of 17 exons and
      spans more than 36 kb. It contains an additional 5' exon and intron (exon and
      intron 1) and an additional 3' exon (exon 17) and intron (intron 16) as compared
      to nramp1, a homologous gene. The additional exons and introns account for much
      of the difference in length between nramp2 (> 36 kb) and nramp1 (12 kb). The exon
      intron borders of nramp2 exons 3-15 are homologous to nramp1 exons 2-14. The
      nramp2 5' regulatory region contains two CCAAT boxes but lacks a TATA box. The 5'
      regulatory region of nramp2 also contains five potential metal response elements
      (MRE's) that are similar to the MRE's found in the metallothionein-IIA gene,
      three potential SP1 binding sites and a single gamma-interferon regulatory
      element. Five single nucleotide mutations or polymorphisms were identified within
      the nramp2 gene. One of these, 1303C-->A, occurs in the coding region of nramp2
      and results in an amino acid change from leucine to isolecine. A polymorphism,
      1254T/C, also occurs in the coding region of nramp2 but does not cause an amino
      acid change. The other 3 polymorphisms are within introns (IVS2 + 11A/G, IVS4 +
      44C/A, and IVS6 + 538G/Gdel). In addition, a polymorphic microsatellite
      TATATCTATATATC (TA)6-7 (CA)10-11 CCCCCTATA (TATC)3 (TCTG)5 TCCG (TCTA)6 was
      identified in intron 3. Analysis of cDNA derived by direct amplification of
      reversed transcribed RNA or cDNA clones isolated from a library provide evidence
      of skipping of exons 10 and 12 of nramp2. Deletion of either of these exons would
      result in a sequence that remains in frame yet would generate a protein that
      would lack transmembrane spanning region 7 or 8 respectively. The deletion of a
      single transmembrane domain would have severe topological consequences. The
      coding region of the nramp2 gene of hemochromatosis patients with or without
      mutations in the hemochromatosis gene, HFE, were examined and found to be normal.
      One hemochromatosis patient, with a normal HFE genotype, was heterozygous for the
      1303C-->A mutation. Furthermore, in an examination of hemochromatosis patients
      with mutant HFE and normal HFE genes, we did not observe a linkage disequilibrium
      of either group with a particular nramp2 haplotype. These data suggest that
      mutations in nramp2 are not commonly associated with hemochromatosis.

PMID- 9642102
TI  - Calpain: a protease in search of a function?

PMID- 9642103
TI  - A second-step splicing activity is conserved from yeast to human.
AB  - We describe a defective HeLa nuclear extract which is particularly deficient in
      step 2 of splicing reaction. With this extract we have studied the conservation
      of a second-step activity from yeast to human cells. We detected a S. cerevisiae
      second-step splicing activity that allows restoration of step 2 of the defective
      HeLa nuclear extract, which indicates that yeast purified fraction has a second
      step activity that is conserved from yeast to human cells. The activity is a
      yeast UsnRNP protein(s) since it is purified with anti-trimethylguanosine by
      immunoaffinity columns.

PMID- 9642104
TI  - Differential regulation of expression of hyaluronan-binding proteoglycans in
      developing brain: aggrecan, versican, neurocan, and brevican.
AB  - We have used a slot-blot radioimmunoassay to quantitate the levels of hyaluronan
      binding chondroitin sulfate proteoglycans in developing rat brain from embryonic
      day 14 (E 14) to eight months postnatal. Recombinant nonhomologous regions of the
      core proteins were used for immunization to obtain polyclonal antibodies specific
      for aggrecan, the alpha and beta domains of versican mRNA splice variants, and N-
      and C-terminal portions of neurocan, while brevican was quantitated using a
      specific monoclonal antibody. The concentration of aggrecan increased steadily
      during brain development up to 5 months of age, when it reached a level that was
      18-fold higher than at E14. Alternatively spliced versican isoforms containing
      the alpha domain of the glycosaminoglycan attachment region were present at a
      relatively low level during the late embryonic and early postnatal period,
      decreased by approximately 50% between 1 and 2 weeks postnatal, and then
      increased steadily in concentration to reach a maximum at 100 days that was 7
      fold that present at 10 days postnatal. In contrast to these results, versican
      isoforms containing the beta domain more than doubled in concentration between
      E14 and birth, after which they decreased by greater than 90% to reach a low
      "mature" level that remained unchanged between 2 and 8 months. The N- and C
      terminal portions of neurocan (produced by a developmentally-regulated
      proteolytic cleavage in the middle of its chondroitin sulfate attachment region)
      both increased in embryonic brain during development, reached a peak in the early
      postnatal period, and then declined thereafter. As in the case of aggrecan, only
      traces of brevican were detected in embryonic brain and its concentration
      increased steadily after birth to reach an adult level that was approximately 14
      fold higher than that present in neonatal brain. These striking and distinctive
      changes in the concentrations of the different members of this family of
      structurally related proteoglycans in developing brain, including changes in
      opposite directions for versican mRNA splice variants, indicate that the
      individual proteoglycans and their isoforms probably serve unique functions
      during nervous tissue histogenesis.

PMID- 9642105
TI  - Effect of mRNA cap structure on eIF-4E phosphorylation and cap binding analyses
      using Ser209-mutated eIF-4Es.
AB  - The in vitro phosphorylation of human recombinant eIF-4E by protein kinase C was
      most effective in the absence of m7GTP, supporting a 'performed complex model' as
      the mRNA binding step of initiation, i. e., eIF-4E first forms an initiation
      complex eIF-4F and is phosphorylated before interacting with mRNA. On the other
      hand, the comparison of m7GTP-binding ability of wild-type eIF-4E with those of
      four Ser209-mutated ones (S209A, S209D, S209E and S209K) showed that the addition
      of anionic charge on Ser209 increases the cap affinity of eIF-4E by repressing
      the release of the cap from the complex, not by increasing the complex formation,
      suggesting the importance of a retractable ionic bridge between Ser209 and Lys159
      in controlling the cap binding by eIF-4E phosphorylation.

PMID- 9642106
TI  - Isolation and characterization of LMC, a novel lymphocyte and monocyte
      chemoattractant human CC chemokine, with myelosuppressive activity.
AB  - By searching the Expressed Sequence Tag (EST) data base, we identified a partial
      cDNA sequence encoding a novel human CC chemokine. The entire cDNA sequence was
      determined and revealed a CC chemokine whose mature protein consisted of 100
      amino acids with predicted molecular weight of 11 kd. The chemokine
      preferantially chemoattracted lymphocytes and monocytes but not neutrophils. It
      was, therefore, named LMC (Lymphocyte and Monocyte Chemoattractant). LMC
      exhibited potent myelosuppressive activity, which was comparable to that of MIP
      1alpha. We identified several bacterial artificial clones (BAC) containing the
      LMC gene along with two human CC chemokine subfamily members; leukotactin-1 (Lkn
      1) and CKbeta8-1/CKbeta8. This data suggests that the LMC gene is located at
      human chromosome 17q which encompasses a human CC chemokine gene cluster.

PMID- 9642107
TI  - A positively charged alpha-lipoic acid analogue with increased cellular uptake
      and more potent immunomodulatory activity.
AB  - alpha-Lipoic acid (LA) is taken up by cells and reduced to its potent dithiol
      form, dihydrolipoate(DHLA), much of which is rapidly effluxed out from cells. To
      improve retention in cells, the LA molecule was modified to confer a positive
      charge at physiological pH. N,N-dimethyl,N'-2-amidoethyl-lipoate was synthesized.
      The protonated form of the new molecule is referred to as LA-Plus. The uptake of
      LA-Plus by human Wurzburg T cells was higher compared to that of LA. Several-fold
      higher amounts of DHLA-Plus, the corresponding reduced form of LA-Plus, were
      detected in LA-Plus treated cells compared to the amount of DHLA found in cells
      treated with LA. At 100 microM, LA did not but LA-Plus inhibited H2O2 induced NF
      kappaB activation and NF-kappaB directed IL-2 receptor expression. Both LA and LA
      Plus synergised with selenium in inhibiting H2O2 induced NF-kappaB activation. At
      150 microM LA-Plus, but not LA, inhibited TNFalpha induced NF-kappaB activation.
      At 5 microM LA-Plus, but not LA, protected against both spontaneous and etoposide
      induced apoptosis in rat thymocytes. LA-Plus is thus an improved form of LA with
      increased therapeutic potential.

PMID- 9642109
TI  - Characterization of human mitochondrial RNase P: novel aspects in tRNA
      processing.
AB  - Human mitochondrial RNase P does not distinguish itself from other RNase P
      enzymes by most of its basic properties. 5' phosphates on tRNA products, strict
      dependence on a divalent cation, independence of ATP or other cofactors, and
      sensitivity to puromycin are generally characteristic for RNase P. Slow
      sedimentation of human mitochondrial RNase P in glycerol gradients suggests a
      molecular weight considerably lower than that of bacterial or nuclear RNase P. In
      contrast to fungi, all putative components of mammalian mitochondrial RNase P are
      encoded by the nucleus. Intriguingly, no indication of the involvement of a trans
      acting RNA was found in mammalian mitochondrial tRNA processing. Mitochondrial
      RNase P is resistant to rigorous treatments with nucleases and exhibits a protein
      like density in Cs2SO4 gradients. Moreover, an analysis of copurifying RNAs
      revealed no putative RNase P RNA candidates. These data suggest that mammalian
      mitochondrial RNase P, unlike its nuclear counterpart or its bacterial relatives,
      is not a ribonucleoprotein but a protein enzyme.

PMID- 9642108
TI  - Glutathione levels determine apoptosis in macrophages.
AB  - Spermine NONOate (SpNO, a nitric oxide donor) induced apoptosis and caspase-3
      activity in the macrophage cell line RAW 267.4. RES cells that have been derived
      from RAW 267.4 cells by repeated exposure to lipopolysaccharide and interferon
      gamma (LPS/INF-gamma), followed by outgrowth of viable cells, are resistant to
      apoptosis and caspase-3 activation upon exposure to SpNO. In this study we have
      determined that RES cells have lower levels of glutathione (GSH) and a higher
      oxidative state than RAW cells. Subsequently, RAW and RES cells were depleted of
      GSH by using l-buthionine-[S,R]-sulfoximine (BSO), a specific inhibitor of GSH
      synthesis. GSH depleted cells did not undergo apoptosis nor demonstrate caspase-3
      activity when they were exposed to SpNO. These results suggest that the redox
      status of the cell is one of the key factors mediating the apoptotic pathway in
      which glutathione plays a critical role in mediating apoptosis via NO* and
      reactive oxygen species (ROS).

PMID- 9642110
TI  - A role of calcineurin in coreceptor regulation during differentiation of Cd4+Cd8+
      T cells.
AB  - The immunosuppressant FK506 inhibits thymocyte positive selection. Calcineurin, a
      FK506-sensitive Ca2+/calmodulin-dependent protein phosphatase, is presumed to be
      involved in this event without direct evidence. We have previously shown that
      moderate stimulation of CD4(+)CD8(+) thymocytes with a combination of the calcium
      ionophore ionomycin and phorbol myristate acetate mimics positive selection
      events including downregulation of CD8 expression. Moderate stimulation of a
      CD4(+)CD8(+) T cell line with the same combination of drugs also induced specific
      downregulation of CD8 expression. FK506 inhibited the CD8 downregulation in both
      cell types. The T cell line was transfected with an expression vector encoding an
      active form of calcineurin. The transfectans remained CD4(+)CD8(+), but became
      CD4(+)CD8(-) or CD4(+)CD8(low) upon stimulation with phorbol myristate acetate
      alone. The extent of the CD8 downregulation was correlated with the expression
      level of the mutant calcineurin. These results suggest that the calcium signal
      for the CD8 downregulation is mainly delivered through calcineurin activation.

PMID- 9642111
TI  - Molecular cloning and expression of human cGMP-binding cGMP-specific
      phosphodiesterase (PDE5).
AB  - A human PDE5 cDNA has been isolated which contains an open reading frame encoding
      an 875 amino acid, 100,012 Da polypeptide, the expression of which yields a
      protein of the predicted size and is capable of hydrolyzing cGMP. The deduced
      amino acid sequence is very similar (95%) to that of bovine PDE5, and comprises a
      conserved cGMP-binding domain and catalytic domain. Northern analysis reveals a
      major and minor transcript of approximately 9 kb and approximately 8 kb
      respectively, thus indicating the existence of at least two splice variants, the
      major form being readily detected in bladder, colon, lung, pancreas, placenta,
      prostate, small intestine, and stomach.

PMID- 9642112
TI  - A novel relative of the very-long-chain acyl-CoA synthetase and fatty acid
      transporter protein genes with a distinct expression pattern.
AB  - Based on its relationship to very-long-chain acyl-CoA synthetase (VLACS), we have
      cloned and identified a novel, VLACS-related (VLACSR) cDNA from mouse liver. The
      2067-bp open reading frame encodes a 689-amino-acid protein with a predicted
      molecular mass of 76.2 kDa. The carboxy-terminal 500 amino acids of VLACSR show
      48% identity and 70% similarity to mouse VLACS and 43% identity and 60%
      similarity to mouse fatty acid transporter (FATP), respectively. In addition, a
      partial cDNA of the human VLACSR ortholog was identified. By Northern blot
      analysis, a 2.6-kb VLACS mRNA was highly abundant only in mouse liver. Low levels
      of shorter mRNAs were present in brain, lung, testes, and spleen (2.5 kb) and in
      skeletal muscle (2.2 kb). In heart, but not in kidney, transcripts undetectable
      by Northern blot analysis could be demonstrated by RT PCR. Southern blot analysis
      indicated single-copy VLACSR genes in the mouse and human genomes.

PMID- 9642113
TI  - Rapid enhancement of high affinity glutamate uptake by glucocorticoids in rat
      cerebral cortex synaptosomes and human neuroblastoma clone SK-N-SH: possible
      involvement of G-protein.
AB  - The rapid effects of glucocorticoids(GCs) on the Na+dependent, high affinity
      uptake of 3[H]-L-glutamate(Glu) in rat cerebral cortex synaptosomes(4 min
      incubation) and human neuroblastoma clone SK-N-SH (10min preincubation and 5 min
      incubation) were investigated. GCs, including corticosterone, corticosterone
      sulfate, hydrocortisone-hemisuccinate and dexamethasone 21-phosphate(DEX) were
      found stimulating Glu uptake. The uptakes in synaptosomes and SK-N-SH cells were
      increased to 117-126% and 121-137% respectively of the control by 10(-6)mol/L
      GCs. The stimulation of GCs was dose-dependent. The maximal effect of DEX in SK-N
      SH cells appeared at10(-7)mol/L, and the least effective dose of DEX was at 10(
      9)mol/L. Guanosine 5-O-(2-thiodiphosphate), an inhibitor of G-protein activation,
      could block the stimulation of GCs. The results indicated that GCs rapidly
      enhance the Na+-dependent high affinity Glu uptake in nerve endings and SK-N-SH
      cells, even at the concentration of physiological conditions, and the G-protein
      on synaptic membranes or SK-N-SH cell membranes might be involved in the effect
      of GCs.

PMID- 9642114
TI  - Identification and cloning of an orphan G protein-coupled receptor of the
      glycoprotein hormone receptor subfamily.
AB  - Mining of the EST database identified a human EST that was predicted to encode a
      novel member of the glycoprotein hormone receptor subfamily. Based on the
      sequence information, the full-length coding region of this gene was isolated and
      sequenced. This gene, designated HG38, is predicted to encode a polypeptide of
      907 amino acid residues with a putative signal peptide sequence at its very N
      terminus. HG38 is most closely related to members of the glycoprotein hormone
      receptor subfamily with approximately 35% overall identity at the protein
      sequence level. As with the glycoprotein hormone receptors, HG38 contains a long
      extracellular domain with a total of 16 leucine-rich repeats. Northern blot
      analysis showed that HG38 was expressed in skeletal muscle, placenta, spinal
      cord, and various regions of the brain. Radiation hybrid mapping placed HG38 into
      human chromosome 12q22-23. HG38 is most likely to be a receptor for a novel class
      of glycoprotein ligands.

PMID- 9642115
TI  - Phagocyte NADPH oxidase p67-phox possesses a novel carboxylterminal binding site
      for the GTPases Rac2 and Cdc42.
AB  - Rac GTPases regulate activation of the phagocyte NADPH oxidase, a multi-component
      enzyme complex that produces superoxide in response to host infection. GTP-bound
      Rac binds to the cytosol protein p67-phox enabling it to participate in oxidase
      assembly. Details of this interaction are poorly understood. Previous studies
      showed that Rac/p67-phox binding is GTP-dependent and that several Rac1 mutants
      lost the ability to activate the oxidase even though they still bound p67-phox.
      Using two hybrid and blot overlay binding methods, we identified a novel binding
      site in the p67-phox C-terminus that binds Rac1, Rac2, and Cdc42, a related
      GTPase which does not activate the oxidase. Binding was independent of the
      GDP/GTP state. We also showed that GTP-Cdc42 binds p67-phox N-terminus similar to
      GTP-Rac. Therefore, Rac binding to p67-phox is not synonymous with NADPH oxidase
      activation, and Rac probably participates in other steps of oxidase activation in
      addition to binding p67-phox.

PMID- 9642116
TI  - Male-associated hypertension in LDL-R deficient mice.
AB  - Hypertension is more common among African Americans than Americans of European
      descent. However, the genetic etiology has not been defined. Similarly,
      lipoprotein (Lp) (a), an independent risk factor for cardiovascular disease, is
      higher among African Americans. To explore the relationship between Lp (a) and
      hypertension, we measured the blood pressure of transgenic mice expressing
      apolipoprotein(a), the unique protein moiety of lipoprotein(a). As controls, we
      also determined blood pressure for apoE deficient mice, low density lipoprotein
      receptor (LDL-R) deficient mice, and wild type C57Bl/6 mice. Apo(a) expression
      was not associated with hypertension. Surprisingly, LDL-R deficient mice
      exhibited male-associated hypertension. This observation could explain the higher
      incidence of atherosclerosis in male LDL-R deficient mice and human familial
      hypercholesterolemia (FH) patients. LDL-R deficient mice were more sensitive to
      photochemically induced cerebral stroke. However, this hypersensitivity was only
      modestly associated with sexual dimorphism. The presented data suggest that LDL-R
      deficiency results in hitherto unrecognized changes in the vascular tone.

PMID- 9642117
TI  - Characterization of a novel liver-specific protein/DNA binding site in the human
      HMG CoA reductase promoter.
AB  - These studies define a novel binding element (site C) within the human HMG CoA
      reductase promoter using a combination of in vitro DNase I footprinting and gel
      mobility shift assays. The factor interacting with site C appears to be
      restricted to the liver, indicating a possible role for this protein in
      regulating hepatic expression of the gene. Studies based on competitive gel
      mobility shift assays and transient co-transfection experiments performed using a
      reporter construct harbouring the promoter of HMG CoA reductase suggest that the
      protein binding to site C may belong to the C/EBP family of transcription
      factors. A factor interacting with this binding element was also identified in
      human liver nuclear protein extracts.

PMID- 9642118
TI  - Tissue restricted expression of two human Frzbs in preadipocytes and pancreas.
AB  - Frzb is a newly discovered family of secreted glycoproteins that function to
      modulate signaling activity of Wnt. Frzb proteins share sequence homology with
      the extracellular domain of the Wnt receptor (frizzled) and are capable of
      binding to Wnt. Thus, Frzb functions to antagonize Wnt activity by sequestering
      Wnt and preventing its binding to the frizzled receptor. Since the initial
      identification of bovine and human Frzb, several related members of this family
      have been isolated from rodent and human. In this paper, we describe the cloning
      and expression of two human frzb homologues termed hFRP-1b and hFRP-2. These
      human FRPs share significant homology to mouse sFRP-1 and sFRP-2 (55 and 98%
      identity at amino acid level, respectively). Northern blot experiments revealed
      that these Frzb homologues have highly restricted tissue distribution. hFRP-1b is
      exclusively expressed in pancreatic tissue while high levels of hFRP-2 were found
      in adipose tissue. In addition, low levels of hFRP-2 were also observed in other
      tissues including heart, pancreas and muscle. Remarkably, FRP-2 is predominantly
      expressed in un-differentiated preadipocytes in both rodent and man. The
      expression of FRP-2 is also significantly reduced in fat pads from obese mice.
      Taken together, these data indicate that distinctive members of the Frzb family
      exhibit different expression patterns in vivo, suggesting their ability to
      modulate diverse aspects of Wnt signaling. The expression and dysregulation of
      sFRP-2 in fat and obesity also suggest a potential roles on the Wnt signaling
      pathway in the pathology of obesity and related metabolic diseases. Molecular
      cloning and expression of these Frzbs will allow detailed molecular and
      biochemical analysis of Wnt-Frzb interaction and their impact on Wnt-Frizzled
      receptor signal transduction.

PMID- 9642119
TI  - Skin cancer chemopreventive effects of a flavonoid antioxidant silymarin are
      mediated via impairment of receptor tyrosine kinase signaling and perturbation in
      cell cycle progression.
AB  - Enhanced tyrosine kinase activity due to aberrant or overexpression of receptor
      and/or non-receptor tyrosine kinases has been implicated in a variety of human
      malignancies including cutaneous neoplasms. Epidermal growth factor receptor
      (EGFR)-mediated tyrosine phosphorylation may be a primary indicator of signal
      transduction regulating cell growth and proliferation. Recent studies have shown
      that skin tumor promoters such as phorbol ester and ultraviolet B radiation
      activate EGFR in mouse skin as well as in cell culture. Similarly, oxidative
      stress, which is implicated in skin tumor promotion, also activates EGFR-mediated
      cell signaling. Since this signaling pathway has been suggested to be involved in
      skin tumor promotion, its impairment by antioxidants may lead to an efficient way
      for skin cancer prevention and therapy. Recently, we showed that silymarin, a
      flavonoid antioxidant, affords exceptionally high to complete protection against
      several skin tumor promoters caused tumor promotion in mouse skin. Employing
      human epidermoid carcinoma cells A431 that contain overexpressed EGFR, in this
      study, we assessed whether the anti-skin tumor promoting effects of silymarin are
      due to its inhibitory effect on EGFR activation and down stream signaling pathway
      leading to perturbations in cell cycle progression. Treatment of cells with
      silymarin resulted in a significant inhibition of ligand-induced activation of
      EGFR with no change in its protein levels. Silymarin treatment also resulted in a
      significant decrease in tyrosine phosphorylation of Shc, an immediate downstream
      target of EGFR, but no change in the protein levels of Shc. The inhibition of
      EGFR activation by silymarin was associated with a highly significant to complete
      inhibition of EGFR intrinsic kinase activity. Cells treated with silymarin also
      showed a significant G2-M arrest in cell cycle progression, and a highly
      significant inhibition of DNA synthesis and cell growth in a dose-dependent
      manner. Taken together, these results suggest that skin cancer chemopreventive
      effects of silymarin are mediated via impairment of EGFR signaling which
      ultimately leads to perturbation in cell cycle progression resulting in the
      inhibition of proliferation and induction of growth arrest.

PMID- 9642120
TI  - Identification and characterization of a new human gene encoding a small protein
      with high homology to the proline-rich region of the SH3BGR gene.
AB  - As part of an effort to identify genes potentially involved in the Down Syndrome
      pathogenesis, in this paper we report the identification and characterization of
      a new human gene (named SH3BGRL), which shows a high homology to the SH3BGR gene,
      previously mapped to the Down Syndrome region of chromosome 21. The SH3BGRL gene
      encodes for a small protein of 114 amino acids, sharing 60% identity and 84%
      conservation on the amino acid level with the middle, proline-rich region of the
      SH3BGR gene and containing a similar SH3 (Scr homology 3) binding motif. The
      SH3BGRL and the proline-rich region of SH3BGR proteins appear to be highly
      conserved, sharing 95 and 98% identity, respectively, with the mouse homologues.
      A 1.9 kb transcript of the SH3BGRL gene has been found in all the tissues
      examined, in contrast with the expression pattern of the SH3BGR gene which is
      transcribed only in heart and skeletal muscle. The SH3BGR gene and its homologue,
      SH3BGRL, could be members of a new family of genes containing a highly conserved
      proline-rich functional domain. The SH3BGRL gene has been mapped by fluorescent
      in situ hybridization to Chromosome Xq13.3.

PMID- 9642121
TI  - Differential expression of alpha3 fucosyltransferases in Th1 and Th2 cells
      correlates with their ability to bind P-selectin.
AB  - One of the key control points in the trafficking of the T cell effector subsets,
      Th1 and Th2, to sites of inflammation is their migration out of the bloodstream.
      The mechanism by which the cells initially adhere to the endothelium is dependent
      on the selectin family of adhesion molecules. Only polarised Th1 cells are
      capable of binding P-selectin despite both Th1 and Th2 cells expressing PSGL-1,
      the P-selectin ligand. This may be due to a secondary modification of PSGL-1 that
      is present on Th1 but not Th2 cells. One key modification of PSGL-1 is the alpha3
      fucosylation of the O-glycans. To address whether the binding of Th1 and Th2
      cells may be regulated by fucosylation, we have studied the expression of the
      alpha3 fucosyltransferases, FucT-IV and VII, using in vitro differentiated mouse
      T cells. Messenger RNA levels for both FucT-IV and VII were found to be higher in
      Th1 than Th2 cells. alpha3 fucosyltransferase enzyme activities were also
      elevated in Th1 cells. The increased expression of the alpha3 fucosyltransferases
      in Th1 cells correlated with the ability of Th1, but not Th2, cells to bind to P
      selectin. Thus, the regulation of the binding of effector T cells to the
      endothelium, and subsequent trafficking to inflammatory sites, may be controlled
      by the fucosylation state of PSGL-1 mediated by the selective expression of the
      alpha3 fucosyltransferases.

PMID- 9642122
TI  - Detection of endogenous biotin-containing proteins in bone and cartilage cells
      with streptavidin systems.
AB  - When utilizing streptavidin systems with Western blots of chondrocyte, osteoblast
      and osteoclast lysates, proteins of the molecular weights 116 kDa, 75 kDa and 67
      kDa were observed to be bound by streptavidin alone. Streptavidin binding could
      not be blocked by pre-incubation with an RGD containing peptide. The same
      proteins were bound by ExtrAvidin which lacks the RGD sequence present in
      streptavidin. Pre-incubation with free biotin completely abolished the binding of
      both streptavidin and ExtrAvidin. The three proteins observed are believed to be
      the biotin containing carboxylases: pyruvate carboxylase, 3-methylcrotonyl
      carboxylase, and propionyl carboxylase. The findings of this study underscore the
      need to apply vigorous controls to distinguish between endogenous biotinylated
      proteins and biotin used as a means to amplify avidin detection systems since a
      wide variety of proteins with relevance to bone and cartilage biology have
      molecular weights similar to the biotin carboxylases.

PMID- 9642123
TI  - Epitope-specific focusing of the immune response to a minimized human chorionic
      gonadotropin analog.
AB  - Minimized proteins have long been used to elicit an immune response to particular
      regions of a protein antigen. Most efforts to derive minimized proteins have
      employed synthetic peptide fragments. This approach works well for linear
      epitopes but poorly for conformational epitopes. Here we describe a homodimeric
      human chorionic gonadotropin (hCG) analog that retains the conformation of
      related parts of hCG and elicits high affinity specific antibodies. This novel
      immunogen displays the tertiary structure of selected loops of the protein but
      lacks structures that could elicit potentially undesirable antibodies.

PMID- 9642124
TI  - Differential expression of alternatively spliced c-erbB-2 mRNA in primary tumors,
      lymph node metastases, and bone marrow micrometastases from breast cancer
      patients.
AB  - We established an RT-PCR method to measure the amount of a 2.3-kb alternatively
      spliced mRNA of the human c-erbB-2/HER-2 proto-oncogene relative to the 4.6-kb
      full-length transcript. For the first time, we demonstrated production of c-erbB
      2 extracellular domains via alternative splicing in breast cancer tissues, lymph
      node and bone marrow micrometastases. In 15 c-erbB-2-positive primary breast
      tumor samples, we found two significantly distinct subgroups: 6/15 had a low
      level of the extracellular fragment, and 9/15 showed an average 4.4-fold higher
      amount of the alternatively spliced mRNA. Additionally, six lymph nodes and six
      bone marrow aspirates from metastatic breast cancer patients were analyzed: 5/6
      lymph nodes and 6/6 bone marrow aspirates were found to produce elevated relative
      amounts of the truncated fragment. The results demonstrate that our method is
      suitable for sensitive detection of c-erbB-2-positive micrometastasis and
      strongly suggest that the alternatively spliced c-erbB-2 variant is involved in
      the development of micrometastasis in breast cancer.

PMID- 9642126
TI  - A functional eukaryotic promoter is contained within the first intron of the hGH
      N coding region.
AB  - Human growth hormone is frequently used as a reporter gene in studies addressing
      the regulation of eukaryotic promoters. Here we present evidence that the first
      intron of the hGH-N coding region contains a novel eukaryotic promoter which is
      able to direct the expression of hGH-N and luciferase reporter genes. The
      corresponding transcriptional initiation site is located downstream of the splice
      acceptor site of exon 2. This internal hGH-N promoter can interfere with the
      transcriptional control elements of a promoter linked to the hGH-N coding region
      and thereby complicate the interpretation of data obtained with hGH-N as a
      reporter gene.

PMID- 9642125
TI  - A matrix metalloproteinase proenzyme activator produced by articular cartilage.
AB  - Matrix metalloproteinases (MMPs) are involved in connective tissue turnover under
      physiological and pathological conditions. MMP activity is regulated by the
      requirement for zymogen activation. This report describes a proMMP-3 activator
      produced by articular cartilage. The activator initiates a step-wise processing
      of proMMP-3 to generate an array of active species. Sequencing of activation
      intermediates demonstrated cleavage on the NH2-terminal side of certain basic
      residues in the MMP-3 propeptide. Metal ion chelators inhibited activator
      dependent proteolysis, and activity was restored by low levels of ZnCl2. These
      catalytic properties suggest similarity to members of the insulinase superfamily
      of metalloendopeptidases with in vitro specificity for single arginine or paired
      basic processing sites in a variety of prohormones. Dibasic sites also exist in
      the propeptides of several MMPs including proMMP-3. This is the first report that
      cartilage produces a potent MMP proenzyme activator, opening the possibility of a
      novel intrinsic activation pathway for catabolic processes in this avascular
      tissue.

PMID- 9642127
TI  - Regulation of osteoprotegerin mRNA levels by prostaglandin E2 in human bone
      marrow stroma cells.
AB  - The recently cloned osteoclastogenesis inhibitory factor, or osteoprotegerin
      (OPG), has been shown to be a potent inhibitor of osteoclast formation. The
      inhibition is believed to be mediated through specific binding of OPG to a cell
      surface ligand on osteoblastic stromal cells. In this report we have studied the
      effect of the bone resorbing agent prostaglandin E2 (PGE2) on OPG mRNA levels in
      primary cultures of human bone marrow stroma cells (hBMSC). PGE2 dose- and time
      dependently down-regulated the mRNA levels of OPG, as measured by RNAse
      protection assay. After 4 hours of stimulation with 1 microM PGE2, OPG mRNA
      levels were significantly decreased. The inhibitory effect was seen at and above
      1 nM of PGE2. To elucidate whether the OPG mRNA levels are regulated via the
      proteinkinase A and/or the proteinkinase C pathways we stimulated cells with
      either forskolin (FSK) or phorbolic ester (PDbu) respectively. FSK (10 microM)
      decreased OPG mRNA levels to 50 % of control, whereas PE (10 nM) upregulated the
      mRNA levels to 250 % of control. These data show that PGE2 down-regulates the
      expression of OPG mRNA in hBMSC, probably via an increase in cAMP. This mechanism
      might be involved in PGE2-induced bone resorption.

PMID- 9642128
TI  - Suppression of type I collagenase expression by antisense RNA in melanoma cells
      results in reduced synthesis of the urokinase-type plasminogen activator
      receptor.
AB  - Previously we reported that suppression of type I collagenase synthesis in human
      melanoma cells with antisense RNA significantly reduced proteolysis of type I and
      type IV collagen matrices (Durko et al., 1997, Biochim. Biophys. Acta 1356, 271).
      Because plasmin is a major activator of the type I collagenase, we assessed the
      impact of type I collagenase suppression on the urokinase/plasmin system of
      proteolysis. Gel zymography revealed the appearance of two new caseinolytic bands
      of Mr 81-83000 in conditioned media of type I collagenase-depleted, but not of
      wild-type cells and these were identified as plasmin bands. This increased
      extracellular plasmin activity coincided with reduced membrane-associated
      plasminogen levels and decreased expression of the urokinase-type plasminogen
      activator receptor at both the mRNA (up to 83% reduction) and cell-surface (up to
      48% reduction) levels, while urokinase mRNA levels remained unchanged. The
      results indicate that in these cells the urokinase/plasmin system is regulated by
      type I collagenase levels.

PMID- 9642129
TI  - The potential of various HIV-1 mutants to inhibit the replication of wild-type
      virus.
AB  - We have previously demonstrated that many of gag mutants of human
      immunodeficiency virus type 1 (HIV-1) inhibited the replication of wild-type (wt)
      HIV-1. In this study, various HIV-1 mutants were systematically analyzed with
      respect to their ability to suppress the replication of wt HIV-1. Sixteen mutants
      of all eight HIV-1 genes other than gag were evaluated for their inhibitory
      effects. Only an env mutant designated NL-Hi efficiently interfered with the
      replication of wt HIV-1 in a single round of infection. The NL-Hi did not affect
      the late replication processes of wt virus, including transcription, translation,
      and assembly/release. Virions produced in the presence of the mutant Env were
      defective for the viral entry process in the early phase of HIV-1 replication
      cycle.

PMID- 9642130
TI  - Expression of peroxisome proliferator-activated receptor gamma (PPARgamma) in rat
      aortic smooth muscle cells.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma), a member of nuclear
      receptors, is expressed at a high level in adipose tissue and plays an important
      role in adipocyte differentiation. In the present study, we identified the
      expression of PPARgamma in rat aortic smooth muscle cells (RASMC) using reverse
      transcription-polymerase chain reaction and gel mobility shift assay. In
      addition, to investigate whether PPARgamma in RASMC is functional or not, we
      examined the effect of two specific ligands for PPARgamma, a thiazolidinedione
      anti-diabetic agent, troglitazone, and 15-deoxy-Delta12,14-prostaglandin J2, on
      the transcriptional activity of PPAR responsive element (PPRE). A significant
      increase in the activity of PPRE by addition of these ligands was found. These
      results suggest that in RASMC, target genes for PPARgamma may be activated by
      specific ligands for PPARgamma through PPRE in their promoters. In conclusion,
      PPARgamma is expressed and functional in vascular smooth muscle cells.

PMID- 9642131
TI  - Expression of the BCL6 gene in the pre- and postnatal mouse.
AB  - Human BCL6, also called LAZ3, is a protein involved in gene regulation and
      abnormal expression of BCL6 and has been implicated in the tumorigenesis of non
      Hodgkin lymphoma. We have analyzed the expression of murin bcl6 in pre- and
      postnatal mouse using in situ hybridization histochemistry and Northern blotting.
      The developing olfactory epithelium in the nasal cavity was the only tissue
      displaying a positive bcl6 mRNA signal in the day 14 embryo. At gestational day
      17, expression was primarily seen in skeletal muscle, olfactory epithelium, and
      thymus, and also in the epithelium lining the upper airways and esophagus. In
      selected tissues from postnatal mouse, bcl6 expression was detected in brain,
      renal cortex, spleen, and thymus. The expression in brain was restricted to the
      pyramidal cell layer of the cerebral cortex and the hippocampus regions CA1 and
      CA2, and the dentate gyrus. Our results show that bcl6 expression is not confined
      only to organs of the lymphatic system, such as spleen and thymus. Thus, bcl6 may
      be active as a regulator of gene transcription in many different cell types,
      including epithelial and nerve cells.

PMID- 9642132
TI  - Effects of oxygen on vascular patterning in Tie1/LacZ metanephric kidneys in
      vitro.
AB  - Tie1 is an endothelial lineage-specific receptor. Using Tie1/LacZ mice we
      previously demonstrated in situ differentiation of glomerular capillaries after
      transplantation of renal precursors into the neonatal nephrogenic kidney cortex.
      We now report studies with Tie1/LacZ metanephric kidneys explanted in vitro at a
      stage when Tie1/LacZ-expressing cells surround nephron precursors but glomeruli
      are unformed. After 4 days of serum-free organ culture in 21% O2, transgene
      expressing vessels regressed. In contrast, in 3% O2, transgene was expressed
      between epithelial tubules by cellular masses containing poorly defined lumens.
      The normal branching of Tie1/LacZ-expressing vessels which occurred in vivo was
      absent in vitro and glomeruli forming in culture lacked capillaries. Similar
      observations were made in wild-type metanephroi using vascular endothelial growth
      factor receptor 2 (Flk1) as an endothelial marker. We speculate that the
      metanephros is hypoxic in vivo to permit endothelial growth but other cues must
      be required for construction of the microcirculation since hypoxia failed to
      elicit normal patterning in vitro.

PMID- 9642133
TI  - Primary structure and molecular modeling of mistletoe lectin I from Viscum album.
AB  - The first three-dimensional structure of the ribosome inactivating protein
      mistletoe lectin I (ML-I) from Viscum album has been modeled on the basis of the
      X-ray structure of castor bean ricin from Ricinus communis. The relative high
      sequence homology and conserved secondary structure enabled accurate modeling.
      The 196 sequence changes between ML-I and ricin could be accomodated with only
      little pertubation in the main chain folding. A close comparison of the primary
      structures of ML-I and ricin is given and the effects of the sequence changes are
      elucidated on the basis of the modeled three-dimensional structure. Differences
      have been identified in the vicinity of the active site, in the high affinity
      galactose binding site and in the interface between the A and B chains, which
      might account for the reduced cytotoxicity of ML-I.

PMID- 9642134
TI  - TNFalpha disrupts mitotic clonal expansion and regulation of retinoblastoma
      proteins p130 and p107 during 3T3-L1 adipocyte differentiation.
AB  - The inhibitory effects of TNFalpha on adipocyte differentiation are well
      described, however, the mechanisms are poorly understood. Early during hormonally
      induced 3T3-L1 preadipocyte differentiation there is a requisite mitotic clonal
      expansion phase that is associated with significant regulation in p130 and p107
      protein levels, two members of the retinoblastoma protein family that regulate
      cell cycle events through interactions with the E2F transcription factors. This
      regulation occurs within the first 24 hours of differentiation (Day 1) and is
      characterized by a transient increase in p107 protein and mRNA levels as well as
      a transient decrease in p130 protein levels. Here we describe that TNFalpha
      disrupts the normal pattern of expression of both p130 and p107 proteins, leading
      to a complete block in mitotic clonal expansion. Interestingly, TNFalpha-treated
      cells enter S-phase as determined by 5-bromo-2'-deoxyuridine uptake experiments,
      but rather than completing cell cycle, they are stimulated to undergo apoptosis.

PMID- 9642135
TI  - p202 prevents apoptosis in murine AKR-2B fibroblasts.
AB  - p202 is an interferon (IFN)-inducible, primarily nuclear, phosphoprotein (52-kDa)
      whose overexpression in transfected cells inhibits colony formation. p202 binds
      to the retinoblastoma tumor suppressor protein and two other members of the
      pocket family proteins (p107 and p130). Moreover, overexpression of p202 in
      transfected cells inhibits the transcriptional activity of E2Fs (E2F-1/DP-1 and
      E2F-4/DP-1), p53, AP-1 c-Fos and c-Jun, NF-kappaB p50 and p65. Here we
      demonstrate that inhibition of endogenous p202 production in murine AKR-2B
      fibroblasts did not result in an increase in cell proliferation. Instead, these
      cells exhibited increased susceptibility to apoptosis in response to decrease in
      serum concentrations in the growth medium. These observations are consistent with
      the notion that normal levels of p202 may be needed for the regulation of cell
      proliferation.

PMID- 9642136
TI  - Silencing of CYP1A1 expression in rabbits by DNA methylation.
AB  - Unlike most experimental animals, treatment of adult rabbits with 3
      methylcholanthrene (MC) does not induce the expression of the CYP1A1 gene. In
      this study, we show that DNA methylation plays one of the key roles in the
      suppression of CYP1A1 gene expression. S1 nuclease protection assay showed that
      the induction of CYP1A1 mRNA by MC occurred in rabbit kidney RK13 cells but not
      in rabbit lung R9ab cells, while aryl hydrocarbon receptor (AhR) and AhR nuclear
      translocator (Arnt) mRNAs were expressed in both cells at similar levels.
      Interestingly, the treatment of R9ab cells with a DNA demethylating agent, 5-aza
      2'-deoxycitidine, resulted in the induction of the expression of the CYP1A1 gene
      by MC. The results indicate that DNA methylation is one of the factors involved
      in the loss of the MC-induced expression of the CYP1A1 gene. Thus, it seemed that
      the binding of the AhR/Arnt complex to the xenobiotic-responsive element (XRE)
      was inhibited by the hypermethylation of CpG dinucleotides within an XRE core
      sequence (5'-CGTG-3'). To explore this possibility, we compared the methylation
      status of XRE in R9ab cells with that in RK13 cells. A bisulfite sequence
      analysis using genomic DNAs from R9ab cells showed that the CpG site within XRE
      was highly methylated on both coding and non-coding strands. In contrast to this
      result, the hypomethylation of XRE was seen in RK13 cells. To examine whether or
      not the binding of the AhR/Arnt heterodimer to XRE is affected by the methylation
      status of XRE, a gel shift assay using a methylated XRE as a probe was carried
      out. As expected, the AhR/Arnt complex could not bind to the methylated XRE. From
      these results, we conclude that the cell type-specific transcription of the
      rabbit CYP1A1 gene is caused by DNA methylation.

PMID- 9642137
TI  - Different effect of diastereoisomers of L-cystathionine sulfoxide on the stimulus
      coupled responses of human neutrophils.
AB  - The priming effect of L-cystathionine sulfoxide, which is one of the unusual
      cystathionine metabolites found in the urine of patients with cystathioninuria,
      on the stimulus-induced superoxide generation by human neutrophils was examined.
      The synthetic L-cystathionine sulfoxide significantly enhanced the superoxide
      generations induced by N-formyl-methionyl-leucyl-phenylalanine [fMLP], opsonized
      zymosan [OZ], arachidonic acid [AA], and phorbol 12-myristate 13-acetate [PMA].
      Then the synthetic L-cystathionine sulfoxide was separated into two
      diastereoisomers, CS-I and CS-II, which showed a peak at 76 and 83 min on
      chromatogram by amino acid analyzer, respectively. CS-I enhanced the superoxide
      generations induced by AA and PMA but not those induced by fMLP and OZ. On the
      contrary, CS-II enhanced the superoxide generations induced by fMLP and OZ but
      not those induced by AA and PMA. The superoxide generation induced by PMA with CS
      I was suppressed by H-7 and was enhanced by genistein, while that by fMLP with CS
      II was suppressed by genistein and was enhanced by H-7.

PMID- 9642138
TI  - Transcriptional activity of RBCK1 protein (RBCC protein interacting with PKC 1):
      requirement of RING-finger and B-Box motifs and regulation by protein kinases.
AB  - The RBCK1 protein was recently identified as a protein kinase C-interacting
      protein with a new type of RBCC (RING-B-Box-Coiled-coil) region, possessing both
      DNA-binding and transcriptional activities unlike other proteins in the RBCC
      protein family (Tokunaga et al. Biochem. Biophys. Res. Commun. 244, 353-359,
      1998). To identify protein motifs in the RBCC region of RBCK1 essential for the
      transcriptional activity, RBCK1 mutant proteins have been constructed and
      analyzed by using the GAL4 chimeric transcription regulator system. We have found
      that both of the RING-finger and the B-Box motifs are indispensable for the
      transcriptional activity of RBCK1. This is the first observation that these
      protein motifs of the RBCC protein family play a crucial role in transcriptional
      activation. In addition, we have examined the effect of co-expression of several
      protein kinases on the transcriptional activity of RBCK1. Protein kinase A (PKA)
      was found to enhance the activity by about eightfold, whereas both ERK
      (extracellular signal-regulated kinase) activator kinase 1 (MEK1) and MEK kinase
      1 (MEKK1) significantly repressed the activity. Because RBCC proteins are
      presumed to act as a proto-oncoprotein, these results suggest that the RBCK1
      protein is involved in the intracellular signaling cascades along with PKA, MEK1,
      and MEKK1 and mediates cell growth and differentiation.

PMID- 9642139
TI  - Artificial imitation of glutathione peroxidase with 6-selenium-bridged beta
      cyclodextrin.
AB  - On the basis of cyclodextrin, 6-selenium bridged beta-cyclodextrin (6-beta-CD-Se
      Se-beta-CD, known as 6-SeCD) was synthesized by the selective tosylation of beta
      cyclodextrin and nucleophilic displacement by sodium hydroselenide to imitate
      glutathione peroxidase (GPX). The GPX activity of diselenide 6-SeCD is 4.3 times
      that of PZ51. The structure of the mimic 6-SeCD was characterized by means of
      laser mass spectroscopy, elemental analysis, IR and 1H NMR. The selenium content
      and its valence in 6-SeCD were determined by means of X-ray photoelectron
      spectra. Kinetics of the mimic showed that its enzymatic behavior was similar to
      that of native GPX.

PMID- 9642140
TI  - Rapid fragmentation of vimentin in human skin fibroblasts exposed to tamoxifen: a
      possible involvement of caspase-3.
AB  - Tamoxifen (TAM), an anti-estrogen compound, is widely used for chemotherapy of
      breast cancer, although the molecular mechanisms underlying TAM cytotoxicity are
      obscure. Here, we show that TAM dramatically caused degradation of vimentin (VIM)
      in human skin fibroblasts, in a time and dose dependent manner. Addition of
      caspase-3 inhibitor, Z-DEVD-FMK, inhibited formation of some fragments of VIM,
      and caspase-3 was proteolytically activated by TAM treatment. Expression of
      functional estrogen receptors were negative in these cells, and neither
      transcription nor protein synthesis was required for TAM-induced degradation of
      VIM. Moreover, quinestrol, an ethinyl estradiol derivative, weakly degraded VIM,
      whereas neither estradiols nor estriol had any effects. Taken together, TAM may
      induce fragmentation of VIM associated with an activation of caspase-3, which may
      be attributed to non-genomic actions of TAM.

PMID- 9642141
TI  - Retinoic acid induction of calcium channel expression in human NT2N neurons.
AB  - Ca2+ channel expression and regulation of intracellular Ca2+ homeostasis were
      studied during retinoic acid (RA)-induced differentiation of the human
      teratocarcinoma cell line Ntera 2/C1.D1 (NT2- cells) into NT2N neurons, a unique
      model of human neurons in culture. The cytosolic Ca2+ level of undifferentiated
      NT2- cells was low (75 +/- 5 nM) and stable under basal conditions, and it was
      only marginally decreased (by 9%) upon removal of extracellular Ca2+. After 10
      microM RA treatment, NT2- cells were irreversibly differentiated into a phenotype
      of neuron-like NT2N cells. Cytosolic Ca2+ level of NT2N neurons was higher (106
      +/- 14 nM) than that of NT2- cells and spontaneously fluctuated (0.208 +/- 0.038
      transients/min) under basal conditions. Although K+ increased 86Rb fluxes in both
      NT2- cells and NT2N neurons, it only increased cytosolic Ca2+ level in NT2N
      neurons. The K+-induced increase in cytosolic Ca2+ in NT2N neurons was
      antagonized by 0.1-10 microM nifedipine or verapamil, 5 microM omega-CgTx GVIA,
      but not by 1 microM omega-agatoxin IVA, 1 microM omega-agatoxin TK, 1 microM FTX
      3.3, or 100 microM Ni+ implicating L- and N-type voltage-dependent Ca2+ channels.
      In L- and N-type channels, but not in P- and Q-types, mRNAs were expressed in
      NT2N neurons as well as NT2- cells. Quantitative analysis of L- and N-type Ca2+
      protein levels showed major differences between NT2- cells and NT2N neurons. In
      NT2- cells, N-type Ca2+ channels were undetectable while L-type channels levels
      were fivefold lower compared to NT2N neurons. Our findings show that L- and N
      type channels are expressed during differentiation of NT2- cells into neurons,
      and that these voltage-dependent Ca2+ channels have a major role in regulating
      intracellular Ca2+ homeostasis and neuronal excitability.

PMID- 9642142
TI  - Selective inhibition by kringle 5 of human plasminogen on endothelial cell
      migration, an important process in angiogenesis.
AB  - Angiogenesis is a multi-step process that includes endothelial cell
      proliferation, migration, basement membrane degradation, and new lumen
      organization. Angiostatin, an internal fragment of plasminogen comprising the
      first four triple disulfide-linked kringle structures, is one of the most potent
      endogenous angiogenesis inhibitors described to date. The kringle 5 domain of
      plasminogen, which shares high sequence homology with the four kringles of
      angiostatin, was previously shown to antagonize endothelial cell growth. We now
      describe that the recombinant kringle 5 of human plasminogen inhibits endothelial
      cell migration with an IC50 (concentration for half maximal inhibition) of
      approximately 500 nM. We demonstrate that the lysine-binding sites of kringle 5
      may not be involved in its anti-migratory activities. The anti-migratory activity
      of kringle 5 is similar to that of angiostatin. Kringle 5 also shows selective
      inhibition on endothelial cells as opposed to other cell types. Relative to its
      native form, reduced kringle 5 displays a significant increase in anti-migratory
      activity, implying that the kringle conformation may shield kringle 5 from
      effectively interacting with endothelial cells. This report thus constitutes the
      first demonstration that kringle 5 of plasminogen is a selective inhibitor for
      endothelial cell migration.

PMID- 9642143
TI  - A critical role for tyrosine residues in His6Ni-mediated protein cross-linking.
AB  - A new type of affinity cross-linking strategy has been developed in which His6
      tagged proteins can be cross-linked to their binding partners in the presence of
      unmodified proteins (D. Fancy, K. Melcher, S. A. Johnston, and T. Kodadek, 1996,
      Chem. Biol. 3, 551-559). The chemistry involves the addition of Ni(II) to the
      His6 tag, followed by oxidation of the metal with a peracid. It is shown here
      that, in addition to the His6 tag, a tyrosine residue placed in close proximity
      to the metal-binding site can strongly stimulate the yield of cross-linked
      product. This finding has important practical implications in the use of the His6
      Ni-based cross-linking reaction for the analysis of multiprotein complexes.

PMID- 9642144
TI  - Identification of the hydrophobic amino acid residues required for heme assembly
      in the rhizobial oxygen sensor protein FixL.
AB  - Rhizobial FixL is a novel heme protein, which senses environmental oxygen tension
      and directs signal transduction via protein phosphotransfer. To identify the
      essential residues for heme assembly in Rhizobium meliloti FixL, we individually
      replaced the 18 invariant hydrophobic amino acid residues (F, I, L, and V) in the
      heme-containing domain with alanine and histidine. Spectroscopic measurements of
      the soluble fractions from fixL recombinant Escherichia coli revealed that V152,
      F162, F170, I172, L185, F226, L230, and F243 as well as the proximal ligand H194
      were indispensable for heme assembly. Autoxidation rates of purified I209H,
      I210A, and I210H were 65-fold, 15-fold, and 15-fold, respectively, faster than
      that of the wild type, although they retained heme in the protein. The absorption
      peak in the Soret region of the ferric I209H or I210H was red-shifted, suggesting
      that the ferric heme is a hexa-coordinate form in these mutants.

PMID- 9642145
TI  - Long-term postmortem survival of mitochondrial genomes in mouse synaptosomes and
      their rescue in a mitochondrial DNA-less mouse cell line.
AB  - Mitochondrial DNA (mtDNA) transfer was carried out from postmortem mouse tissues
      to mouse mtDNA-less (rho0) cells to determine how long it takes for autolysis of
      mtDNA after death and whether mtDNA in postmortem tissues can recover its
      function in rho0 cells. The results showed that mtDNA was stable in postmitotic
      tissues stored at 4 degreesC. Moreover, mtDNA in postmortem brain tissues stored
      for up to 1 month still retained functional properties, causing complete recovery
      of mitochondrial respiratory function, when it was transferred to rho0 cells.
      These observations suggest that mtDNA in brain tissue can survive for 1 month
      after death and can start replication and gene expression in rho0 cells without
      showing any functional defects. This procedure might be applied to human autopsy
      brain tissues for examination of the influence of accumulated somatic mutations
      in mtDNA from aged subjects.

PMID- 9642146
TI  - Induction of apoptosis in murine macrophages by Mycobacterium tuberculosis is
      reactive oxygen intermediates-independent.
AB  - Infection with Mycobacterium tuberculosis induces apoptosis in murine macrophage
      lines. Resistant macrophages B10R (Bcgr) are more prone to undergo apoptosis than
      susceptible B10S (Bcgs) macrophages. Apoptosis and inhibition of intracellular
      growth of the mycobacteria seem to be dependent on the production of nitric
      oxide, since both can be reverted by aminoguanidine (AMG). Although B10R
      macrophages produce more superoxide anion than B10S macrophages after infection
      with M. tuberculosis, reactive oxygen intermediate (ROIs) scavengers did not
      affect uptake of 3H-uracil incorporation by the mycobacteria nor the induction of
      apoptosis. These results further suggest that both phenomena are dependent on the
      production of nitric oxide by the infected macrophages.

PMID- 9642147
TI  - Lack of protection against oxidative modification of LDL by avian HDL.
AB  - Human and murine high density lipoprotein (HDL) has previously been shown to
      decrease the accumulation of lipid peroxides on low density lipoprotein (LDL)
      under oxidising conditions. Several lines of evidence, including the
      ineffectiveness of HDL from paraoxonase knockout mice, suggest that paraoxonase
      (PON1) located on HDL is responsible for its protective effect against lipid
      peroxidation. In this report we compare the effect of HDL from chicken, turkey
      and ostrich with human HDL on lipid peroxidation of LDL. Avian serum lacked PON1
      activity and PON1 immunoactivity was also absent by ELISA and Western blotting
      whereas all three techniques detected PON1 in a variety of non-avian species
      (cow, guinea-pig, rat, sheep, mouse, hamster, monkey and rabbit). Platelet
      activating factor acetyl hydrolase (PAFAH) activity was also absent from avian
      serum. Avian HDL isolated from plasma when incubated with human LDL was
      ineffective in preventing the Cu2+-induced accumulation of lipid peroxides on
      this lipoprotein whereas human HDL under the same conditions was highly effective
      in this respect. Avian LDL was much more resistant to oxidation than human LDL,
      perhaps explaining the lack of HDL-PON1 and PAFAH. We conclude that these
      findings provide further evidence than PON1 has an important role in the
      antiatherogenic/anti-inflammatory effects of HDL and that avian HDL can provide a
      valuable model which complements the use of HDL from paraoxonase knockout mice in
      the investigation of PON1 and PAFAH.

PMID- 9642148
TI  - KDEL motif interacts with a specific sequence in mammalian erd2 receptor.
AB  - The ER retention of lumenal proteins is achieved by a process which involves
      binding of escaped proteins via the C-terminal KDEL-tags to a KDEL receptor (erd2
      receptor) in a post-ER compartment and return of the protein-receptor complex
      back to the ER. The transmembrane topology of the human KDEL receptor, which is
      an integral membrane protein, has been proposed. We have synthesised sets of
      cellulose-bound overlapping peptides covering the complete se quence of the
      receptor to study the interaction of the erd2 receptor with lumenal ER proteins,
      CaBP1 and CaBP2. At the next stage, the proposed lumenal loops of the receptor
      were more closely mapped. A short sequence, essential for the protein binding to
      the most efficient binding site of the receptor, was identified as 22KIWK25,
      which is in accordance with one of the proposed structural models of the
      receptor. The binding was of high specificity and was almost completely inhibited
      by KDEL-containing soluble peptides. The phosphorylation state of CaBP1/CaBP2 did
      not affect their binding to the KDEL receptor.

PMID- 9642149
TI  - Detection and analysis of four polymorphic markers at the human monoamine oxidase
      (MAO) gene in Japanese controls and patients with Parkinson's disease.
AB  - Monoamine oxidase (MAO), which exists in two forms (MAOA and MAOB), plays an
      important role in the oxidative metabolism of neurotransmitters such as dopamine,
      and has been implicated in the etiology of Parkinson's disease (PD). Individual
      variations in the activity of these enzymes appear to be genetically determined,
      and these genetic variations appear to be predominantly mediated by the MAO
      locus. Here, we detected and analyzed four polymorphic markers in the MAO gene
      using a polymerase chain reaction method in 228 Japanese controls (102 males and
      126 females) and 68 patients with PD (30 males and 38 females). Although the
      analysis of the MAOA marker demonstrated no overall association between its
      alleles and PD, a significant difference in the frequency of one particular MAOA
      allele between controls and patients with PD was found. Moreover, in a comparison
      of the distribution of the full haplotypes at the MAOA locus, there was a
      significant difference in the frequency of one particular haplotype between male
      controls and patients with PD. In the MAOB polymorphism, there was no difference
      in the distribution of alleles between them. These findings support the
      hypothesis that the MAOA gene may affect the susceptibility of individuals to PD
      among MAOA polymorphic loci.

PMID- 9642150
TI  - pp120, a substrate of the insulin receptor tyrosine kinase, is associated with
      phosphatase activity.
AB  - pp120, a plasma membrane glycoprotein, is phosphorylated on Tyr488 by the insulin
      receptor tyrosine kinase. This requires basal phosphorylation on Ser503 by cAMP
      dependent serine kinase. Phe513, the other tyrosine residue in the intracellular
      domain, does not undergo insulin-stimulated phosphorylation. Phe488 mutation
      abolished basal and insulin-stimulated phosphorylation, whereas, Phe513 plus
      Phe488 mutation markedly decreased the effect of insulin on pp120 phosphorylation
      without altering basal phosphorylation in intact cells. To investigate whether
      basal phosphorylation of pp120 is regulated by a phosphatase activity that
      requires Tyr513, in vitro phosphorylation assays using partially purified
      glycoproteins from stably transfected NIH 3T3 cells were performed in the absence
      of phosphatase inhibitors. Wild-type pp120 was promptly dephosphorylated,
      whereas, Y513F pp120 was not. Decreasing pp120 expression by antisense cDNA
      transfection proportionally decreased phosphatase activity in H4-II-E hepatoma
      cells measured by the p-nitrophenyl phosphate assay. This suggests that pp120 is
      associated with phosphatase activity that requires an intact Tyr513 residue.

PMID- 9642151
TI  - Calcium-independent activation of extracellular signal-regulated kinases 1 and 2
      by cyclic strain.
AB  - We have previously demonstrated that cyclic strain induces extracellular signal
      regulated kinases 1 and 2 (ERK1/2) activation in endothelial cells (EC). The aim
      of this study was to investigate the effect of Ca2+ on the activation of ERK1/2.
      Bovine aortic EC were pretreated with a chelator of extracellular Ca2+,
      ethylaneglycol-bis(aminoethylether)-tetra-acetate (EGTA), a depleter of Ca2+
      pools, 2,5-Di-(tert-butyl)-1,4-benzohydroquinone (BHQ), or a Ca2+ channel
      blocker, GdCl3, and subjected to an average 10 % strain at a rate of 60
      cycles/min for 10 min. BHQ and GdCl3 did not inhibit the strain-induced ERK1/2
      activation. Chelation of normal extracellular Ca2+ (1.8 mM) medium with EGTA (3
      mM) acutely stimulated baseline phosphorylation and activation of ERK1/2, thereby
      obscuring any strain-induced activation of ERK1/2. However, in EC preincubated
      for 24 hours in Ca2+-free medium, elevated baseline phosphorylation was minimally
      activated by EGTA (200 microM) such that cyclic strain stimulated ERK1/2 in the
      presence or absence of BHQ. These results suggest a Ca2+ independence of the
      ERK1/2 signaling pathway by cyclic strain.

PMID- 9642152
TI  - Alternative splicing of the mRNA coding for the human endothelial angiotensin
      converting enzyme: a new mechanism for solubilization.
AB  - Angiotensin converting enzyme (ACE) is a zinc metalloprotease anchored in the
      plasma membrane with a carboxy-terminal hydrophobic domain. In addition, the
      existence of a soluble form of ACE lacking the transmembrane domain has been
      reported. We show evidence for the existence of an mRNA specific for this isoform
      produced by alternative splicing. In human umbilical vein endothelial cells, two
      ACE mRNAs of different length (4.3 and 3.5 kb) were detected by Northern blot.
      Ribonuclease protection assays and the sequence of a PCR-amplified cDNA fragment
      show that the shortened ACE mRNA lacks the exons coding for the transmembrane
      domain of the protein. As this mRNA could be the source of soluble ACE, plasma
      ACE activity may be regulated on the level of mRNA processing.

PMID- 9642153
TI  - Effect of eicosapentaenoic acid on glucose-induced diacylglycerol synthesis in
      cultured bovine aortic endothelial cells.
AB  - Hyperglycemia has been postulated to increase diacylglycerol (DAG) level through
      de novo synthesis pathway and subsequently activate protein kinase C (PKC) in
      vascular cells, possibly leading to vascular dysfunction associated with
      diabetes. In this study, we examined the effect of eicosapentaenoic acid (EPA) on
      high glucose-induced increase in DAG level in cultured aortic endothelial cells
      (ECs). In ECs, total DAG level was significantly increased in the cells cultured
      with high glucose levels (400 mg/dl) compared with the cells with normal glucose
      levels (100 mg/dl). The addition of EPA completely prevented high glucose-induced
      increase in total DAG level. In contrast, other common fatty acids such as
      palmitate and oleate significantly stimulated DAG syntheisis, although
      arachidonate did not affect it. High glucose level significantly stimulated the
      incorporation of 3H-palmitate into DAG, while it did not affect the incorporation
      of 3H-arachidonate into DAG. The addition of EPA completely prevented the high
      glucose-induced increase in 3H-palmitate incorporation into DAG, while it did not
      affect the 3H-arachidonate incorporation. These findings suggest that EPA can
      prevent high glucose induced-increase in DAG level in ECs, probably by
      specifically inhibiting de novo synthesis at the step of acylation. EPA may be
      one of the candidates for clinical agents normalizing activation of DAG-PKC
      pathway in diabetic vascular tissues and preventing vascular complications
      associated with diabetes.

PMID- 9642154
TI  - Nonylphenol ethoxylates, but not nonylphenol, are substrates of the human
      multidrug resistance P-glycoprotein.
AB  - Alkylphenol ethoxylates are surfactants that are commonly used in industry and in
      home care products. They are broken down by anaerobes to yield toxic
      environmental pollutants such as nonylphenol. In this study, we tested whether
      nonylphenol ethoxylates and their most common biodegradation product,
      nonylphenol, were substrates of human P-glycoprotein. In vivo and in vitro assays
      showed that the enzyme interacts with a wide variety of nonylphenol ethoxylate
      compounds, but not with nonylphenol. These results suggest that P-glycoprotein
      can protect organisms from the toxic and estrogenic effects of nonylphenol
      ethoxylates, but not from the major biodegradation product, nonylphenol.

PMID- 9642155
TI  - Studies on the mechanism of oxidative modification of human glyceraldehyde-3
      phosphate dehydrogenase by glutathione: catalysis by glutaredoxin.
AB  - In this report the protein human glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
      has been examined to clarify the roles of (a) direct oxidation and (b) thiol
      disulphide exchange (with glutathione disulphide) on the modification of its
      catalytic activity. An in vitro system using purified human GAPDH and [35S]-GSSG
      (glutathione disulphide), has permitted clarification of these possibilities by
      showing that S-glutathionylation of GAPDH does not result in an inactivation of
      the enzyme. Rather, the direct oxidation of GAPDH with hydrogen peroxide is
      responsible for inhibition of the catalytic activity of the protein. Furthermore,
      pre-treatment of the enzyme with hydrogen peroxide enhances the formation of
      glutathione-GAPDH mixed disulphides in the presence of glutathione disulphide.
      This may serve as a molecular "switch" directing the protein to other reported
      functions in the cell. It is also shown that the efficiency of S
      glutathionylation of either native or oxidised GAPDH is enhanced by the presence
      of recombinant glutaredoxin (thiol transferase) of either bacterial or human
      origin. Under the conditions of analysis the glutaredoxin itself is also shown to
      readily undergo S-glutathionylation external to its active site. Taken together,
      the data indicate the complexity of mechanisms likely to be involved in
      regulating cellular proteins during oxidative stress and implicate controlled
      enzyme-catalysed S-glutathionylation as a potential selectivity factor in the
      redox modification of protein function by glutathione.

PMID- 9642156
TI  - Association of insulin receptor substrate 3 with SH2 domain-containing proteins
      in rat adipocytes.
AB  - We have recently purified and cloned a new member of the insulin receptor
      substrate family, designated insulin receptor substrate 3 (IRS-3), from rat
      adipocytes. The amino acid sequence of IRS-3 shows multiple potential sites for
      tyrosine phosphorylation in motifs which engage specific SH2 domain-containing
      proteins. In order to determine which SH2 domain proteins complex with IRS-3, we
      have searched for coimmunoprecipitation from lysates of untreated and insulin
      stimulated adipocytes. Phosphatidylinositol 3-kinase and the tyrosine phosphatase
      SHP-2 complexed with the tyrosine phosphorylated form of IRS-3, whereas the
      phospholipase Cgamma did not, and the adaptor Grb2 did so to a much lesser
      extent. These findings complete the survey of SH2 domain proteins associated with
      each of the four known members of the IRS family and provide the framework for
      further analysis of the role of IRS-3 in insulin signaling.

PMID- 9642157
TI  - Cyclic glucans produced by the intramolecular transglycosylation activity of
      potato D-enzyme on amylopectin.
AB  - Potato D-enzyme catalyses an intramolecular transglycosylation reaction on
      amylose to produce cycloamylose, a novel cyclic alpha-1, 4 glucan. To determine
      if a similar activity could be observed with a high molecular weight branched
      substrate, recombinant potato D-enzyme was incubated with amylopectin. The
      substrate was converted into two fractions of lower molecular mass. Fraction I
      comprised 15% cyclic molecules of which the majority contained both alpha-1,4 and
      alpha-1,6 links. These were shown to be branched molecules with branches shorter
      than those in amylopectin. Fraction II comprised 80% cyclic molecules of which
      the majority contained only alpha-1,4 links (cycloamylose). Since fraction II
      appeared before fraction I, we propose that D-enzyme first catalysed the
      cyclisation of the outer side chains of amylopectin and then the cyclisation of
      inner chains to produce branched clusters. These results demonstrate that D
      enzyme can catalyse the transfer of branched glucans, and suggest novel ways in
      which it may participate in starch metabolism in plants.

PMID- 9642159
TI  - Inter-organ leptin exchange in humans.
AB  - To assess the individual role of splanchnic organs, kidney, and peripheral
      tissues on leptin metabolism, leptin exchange across the splanchnic bed, kidney,
      and leg has been evaluated by the arterio-venous technique in post-absorptive non
      obese subjects. Leptin levels in the hepatic and renal veins were significantly
      lower (p < 0.001), while femoral vein levels were consistently greater (p < 0.05)
      than in the artery. The fractional extraction of leptin, namely the percentage of
      arterial leptin extracted, was greater in splanchnic organs (16%) than in the
      kidney (9.5%). Urinary excretion of leptin was undetectable in most subjects,
      indicating that leptin is degraded within the kidney. There was no correlation
      between fractional extraction of leptin and glomerular filtration rate, whereas
      leptin fractional extraction was directly related to renal plasma flow (p =
      0.017). Renal leptin clearance was about 50% of the glomerular filtration rate.
      Our data demonstrate that both splanchnic organs and the kidney cooperate in the
      disposal of leptin, while peripheral tissues add significant amounts of leptin to
      the circulation. In non-obese subjects the contribution of the kidney to whole
      body clearance is no more than 50%. The removal of leptin by the kidney depends
      on renal plasma flow but not on glomerular filtration rate or filtered leptin.

PMID- 9642158
TI  - Up-regulation of uncoupling protein 3 (UCP3) mRNA by exercise training and down
      regulation of UCP3 by denervation in skeletal muscles.
AB  - In skeletal muscles, increased utilization of lipids and carbohydrates
      accompanied with increased energy expenditure has been observed during and after
      exercise. UCP3, mitochondrial uncoupling protein, is expressed in skeletal
      muscles. We investigated UCP3 mRNA levels in exercise training mice which
      increased energy expenditure and in sciatic nerve-denervated mice which decreased
      energy expenditure. Mice exercised by 2 wk swimming had 14- to 18-fold increases
      of UCP3 mRNA in skeletal muscles 3 h after the last swimming, but no increases of
      UCP1 mRNA in BAT and of UCP2 mRNA in WAT. However, 22 h after exercise, UCP3 mRNA
      increases observed in skeletal muscles 3 h after exercise returned to sedentary
      levels. Similar transient increases of UCP3 mRNA were observed in 1 wk treadmill
      running training or a single exercise bout. In denerved gastrocnemius, GLUT4 and
      UCP3 mRNA decreased by 58 and 45%, respectively. These data indicate that UCP3
      may have a role for fine adjustments of energy expenditure and that up-regulation
      of UCP3 mRNA may be a defense mechanism against extra energy supply to consume
      extra energy in skeletal muscles.

PMID- 9642161
TI  - Specific detection of sialyl Lewis X determinant carried on the mucin GlcNAcbeta1
      ->6GalNAcalpha core structure as a tumor-associated antigen.
AB  - Sialyl Lewis X serves as a ligand for selectins and is proposed to be implicated
      in hematogenous metastasis of cancers. When a cultured human breast cancer cell
      line, MCF-7, which does not express sialyl Lewis X, was transfected with human
      fucosyltransferase VI cDNA, a strong expression of sialyl Lewis X was induced on
      transfectant cells. The transfectant cells were found to be also reactive to the
      antibody NCC-ST-439, which was initially raised against human gastric cancer
      cells and later was shown to recognize a tumor-associated carbohydrate antigen in
      breast, gastric, and colon cancers. This suggested that the antigen recognized by
      NCC-ST-439 is closely related to sialyl Lewis X. Subsequent studies indicated
      that NCC-ST-439 specifically reacts to NeuAcalpha2-->3Galbeta1-->4(Fucalpha1-
      >3)GlcNAcbet a1-->6GalNAcalpha1 -->R, the sialyl Lewis X on the mucin GlcNAcbeta1
      ->6 GalNAcalpha structure. The antibody was not reactive to the conventional
      sialyl Lewis X determinants on straight and/or branched polylactosamine
      structures including NeuAcalpha2-->3Galbeta1-->4(Fucalpha1-->3)GlcNAcbet a1-
      >3Galbeta1-->4 Glcbeta1-->R and NeuAcalpha2-->3Galbeta1-->4(Fucalpha1-
      >3)GlcNAcbet a1-->6Galbeta1-->4 Glcbeta1-->R. This was in clear contrast to most
      of the known anti-sialyl Lewis X antibodies, which do not discriminate internal
      structures carrying the sialyl Lewis X determinant. On the other hand, the newly
      generated monoclonal antibody GSC154-27 had a specificity completely the reverse
      of the specificity of NCC-ST-439 in that it was strongly reactive to the
      conventional sialyl Lewis X determinants in straight and branched polylactosamine
      structures, while far less reactive to the sialyl Lewis X determinant on the
      mucin GlcNAcbeta1-->6GalNAcalpha core structure. A set of these two antibodies
      would be useful in discriminating the molecular species of sialyl Lewis X
      expressed by malignant cells and in studying their functional significance.

PMID- 9642160
TI  - Expression of 5-lipoxygenase and 5-lipoxygenase-activating protein mRNAs in the
      peripheral blood leukocytes of asthmatics.
AB  - Leukotrienes are a family of arachidonic acid metabolites with potent biological
      activities such as bronchoconstriction and leukocyte chemotaxis. Recent evidence
      has demonstrated that the 5-lipoxygenase (5-LO) and 5-lipoxygenase-activating
      protein (FALP) products of arachidonic acid metabolism, leukotriene C4, D4 and
      E4, were increased in the serum and the urine of asthmatic patients. Therefore,
      we examined the expression of 5-LO and FLAP mRNAs in the peripheral blood
      leukocytes (PBL) of 10 asthmatics and 10 controls. Both 5-LO and FLAP mRNAs of
      PBL in the asthmatic group were found to be significantly increased compared with
      those in the control group. These data suggest that up-regulation of 5-LO and
      FLAP mRNAs might be involved in the increased leukotriene synthesis and play an
      important role in the pathogenesis of asthma.

PMID- 9642162
TI  - Phosphorylation of alphaB-crystallin and HSP27 is induced by similar stressors in
      HeLa cells.
AB  - Three members of the small heat shock protein family, alphaA-, alphaB-crystallin,
      and HSP27, confer thermoresistance upon their overexpression in mammalian cells.
      Phosphorylation, in conjunction with the molecular chaperone-like activity of
      these small HSPs, is believed to be important for this in situ functional
      property. We here report the influence of heat shock and other kinds of stress on
      the phosphorylation of alphaA-, alphaB-crystallin, and HSP27 in stably
      transfected HeLa cells. It is observed that alphaB-crystallin becomes
      phosphorylated upon exposure to the same inducers as is HSP27, although to a
      lesser extent. In contrast, phosphorylation of alphaA-crystallin is very low upon
      heat stress and even absent when other stressors are used. This indicates that
      phosphorylation is not in all instances essential for the stress protective
      functioning of the various small HSPs.

PMID- 9642163
TI  - Interleukin-2 induces N-glycosylation in T-cells: characterization of human
      lymphocyte oligosaccharyltransferase.
AB  - We have investigated the enzyme mediating N-glycosylation in "resting" and
      activated lymphocytes. Normal peripheral blood lymphocytes (PBLs) were found to
      have low activity for glycosylation of a synthetic glycan acceptor peptide. N
      glycosylation activity increased 10-fold after mitogen activation of PBLs. N
      glycosylation activity remained elevated during long-term culture and expansion
      of human lymphocytes when growth was supported by interleukin-2. To our
      knowledge, this is the first biochemical evidence for induction of endoplasmic
      reticulum functions during T-cell activation. The enzyme mediating N
      glycosylation in lymphocytes was localized predominantly but not entirely to a
      microsomal organelle by subcellular fractionation. After solubilization and 85
      fold purification from salt-washed microsomes, the enzyme preparation contained
      four predominant proteins. N-terminal sequence analysis identified the proteins
      as ribophorin I, ribophorin II (doublet), and a 50-kDa homologue of Wbp1, a yeast
      protein essential for N-glycosylation.

PMID- 9642166
TI  - Introduction: Processing eukaryotic mRNAs.

PMID- 9642164
TI  - Synergistic activation of transcription by physiologically unrelated
      transcription factors through cooperative DNA-binding.
AB  - Most eukaryotic promoters contain binding sites for several different
      transcription factors, which often act synergistically. Mechanistically, synergy
      is ascribed either to cooperative DNA-binding of the factors to the promoter or
      to some type of "multiple contact" mechanism in which each activator performs a
      different task in stimulating the transcription machinery. Here, it is shown that
      the yeast activators Gal4 and Put3 bind to DNA cooperatively in vivo and can
      activate transcription synergistically from certain synthetic promoters.
      Normally, Gal4 and Put3 bind to completely different promoters and activate
      physiologically unrelated sets of genes and it is extremely unlikely that they
      have evolved direct protein-protein contacts. These studies add to a growing body
      of evidence that binding of proteins to nearby sites in chromatin is
      intrinsically cooperative and suggest that many examples of synergy ascribed to
      multiple contact mechanisms may instead involve non-traditional cooperative DNA
      binding.

PMID- 9642167
TI  - RNA localization in Xenopus oocytes.
AB  - The transport and localization of mRNAs within Xenopus oocytes contributes to an
      asymmetry that determines axis formation in the embryo. Several mRNAs become
      localized along the animal-vegetal axis. The mitochondrial cloud, a specialized
      cytoplasmic compartment which contributes to the formation of germ plasm, and the
      endoplasmic reticulum play important roles in sorting and localizing these RNAs.
      As in other species and cell types, the localization of RNAs in Xenopus oocytes
      is directed by signals in the 3' untranslated regions of the transcripts.
      Cytoplasmic proteins that interact with these signals are being identified, as
      are the links between RNA localization, intracellular organelles and early
      embryonic development.Copyright 1997 Academic Press Limited.

PMID- 9642168
TI  - Control of mRNA stability and translation during Drosophila development.
AB  - Translational control of mRNAs regulates the spatio- temporal production of the
      proteins they encode. Further refinement of mRNA and protein distribution
      patterns is brought about by regulation of transcript stability. Genetic and
      molecular analyses in Drosophila can provide unparalleled insight into the
      developmental functions of the modulation of mRNA translation and stability.
      These mechanisms play a key role in regulating the production of cell fate
      determinants, cell cycle regulators and molecular chaperones.Copyright 1997
      Academic Press

PMID- 9642169
TI  - Translational control of development in C. elegans.
AB  - Translational control by the 3'untranslated regions (3'UTRs) of mRNAs contributes
      to important events throughout the development of C. elegans. In oocytes and
      early embryos, maternal mRNAs are controlled by 3'UTR elements to restrict
      translation of their protein products to specific blastomeres. Localized
      translation is probably critical for specifying blastomere identity. In both
      germline and somatic cells, mRNAs from sex determining genes are translationally
      repressed by 3'UTR controls. These controls balance the activities that specify
      male and female cell fates. During larval development, the temporal sequence of
      cell lineages requires 3'UTR-mediated regulation of heterochronic genes by a
      small non-protein coding RNA. We review what is known about these translational
      control mechanisms in C. elegans. This overview illustrates that translational
      control by 3'UTR elements is a powerful mechanism for regulating the expression
      of multiple gene products in diverse cell types during development of a multi
      cellular animal.Copyright 1997 Academic Press Limited.

PMID- 9642170
TI  - Novel functions for 'nuclear factors' in the cytoplasm: the Sex-lethal paradigm.
AB  - In recent years, novel functions for a number of nuclear factors have been
      uncovered in the cytoplasm, mainly at the level of translation. These factors
      behave as multifunctional regulators of gene expression and many play key roles
      in cell differentiation and development. One of the best characterized examples
      is that of Sex-lethal (SXL), an RNA-binding protein that is expressed in female
      Drosophila flies and controls sex determination and dosage compensation. Recent
      findings indicate that SXL, a paradigmatic regulator of splicing, also controls
      translation of target mRNAs. This review attempts to summarize this evidence and
      provide an overview of 'nuclear factors' with roles in translation.Copyright 1998
      Academic Press Limited

PMID- 9642171
TI  - The U7 snRNP and the hairpin binding protein: Key players in histone mRNA
      metabolism.
AB  - Animal replication-dependent histone mRNAs are subject to several post
      transcriptional regulatory processes. Their non-polyadenylated 3' ends are formed
      preferentially during S phase by a unique nuclear cleavage event. This requires
      the base pairing between U7 snRNA and a histone spacer element 3' of the cleavage
      site. Cleavage occurs preferentially after adenosine, at a fixed distance from
      the hybrid region. A conserved RNA hairpin just upstream of the cleavage site is
      recognised by the hairpin binding protein (HBP) that acts as an auxiliary
      processing factor, stabilising the interaction of the histone pre-mRNA with the
      U7 snRNP. The interaction between HBP and the RNA hairpin is very stable and HBP
      is also found associated with histone mRNAs on polysomes. The hairpin and
      presumably, HBP are also required for nuclear export and translation of histone
      mRNA. Furthermore, histone mRNAs are selectively destabilised in the G2 phase or
      upon inhibition of DNA synthesis and this regulation is also associated with the
      hairpin. Recently, HBP-encoding cDNAs were isolated from various organisms.
      Human, mouse and Xenopus laevis HBPs are similar, while the Caenorhabditis
      elegans protein has significant homology to the others only in a central RNA
      binding domain.Copyright 1997 Academic Press Limited

PMID- 9642172
TI  - The role of elav-like genes, a conserved family encoding RNA-binding proteins, in
      growth and development.
AB  - The elav gene is the prototype for a developmental regulator encoding a tissue
      specific RNA-binding protein. The family of elav-like genes includes multiple
      members that are expressed in the nervous system at different times during
      development and also one that is expressed in all tissues. The elav-like proteins
      are proposed to function by binding to specific mRNAs and regulating their
      expression to control a developmental program. Consistent with this model, the
      overexpression of some elav-like genes results in an alteration in the
      developmental fates of some cells. Potential mRNA targets for these proteins have
      been identified along with functions in alternative RNA processing, cytoplasmic
      polyadenylation, and mRNA stability. This diversity of post-transcriptional
      regulatory events may be due to combinatorial interactions with other RNA-binding
      proteins and multiple effectors of RNA regulation.Copyright 1997 Academic Press
      Limited

PMID- 9642173
TI  - Introduction: Proteolytic maturation of secretory proteins.

PMID- 9642174
TI  - Introduction: Adaptation mechanisms.

PMID- 9642175
TI  - Introduction: The green signal for plant pattern formation.

PMID- 9642176
TI  - Information processing by RNA polymerase: recognition of regulatory signals
      during RNA chain elongation.

PMID- 9642177
TI  - Establishment of prespore-specific gene expression in Bacillus subtilis:
      localization of SpoIIE phosphatase and initiation of compartment-specific
      proteolysis.
AB  - Immunofluorescence microscopy was used to study the establishment of compartment
      specific transcription during sporulation in Bacillus subtilis. Analysis of the
      distribution of the anti-anti-sigma factor, SpoIIAA, in a variety of mutant
      backgrounds supports a model in which the SpoIIE phosphatase, which activates
      SpoIIAA by dephosphorylation, is sequestered onto the prespore face of the
      asymmetric septum. Thus, prespore-specific gene expression apparently arises as a
      result of the compartmentalization of SpoIIE protein. The results also suggest
      the existence of at least two compartment-specific programs of proteolysis, one
      dependent on the mother cell-specific sigma factor sigma E and the other
      dependent on the prespore-specific sigma factor sigma F.

PMID- 9642178
TI  - A complex pattern of traveling stripes is produced by swimming cells of Bacillus
      subtilis.
AB  - Motile cells of Bacillus subtilis inadvertently escaped from the surface of an
      agar disk that was surrounded by a fluid growth medium and formed a migrating
      population in the fluid. When viewed from above, the population appeared as a
      cloud advancing unidirectionally into the fresh medium. The cell population
      became spontaneously organized into a series of stripes in a region behind the
      advancing cloud front. The number of stripes increased progressively until a
      saturation value of stripe density per unit area was reached. New stripes arose
      at a fixed distance behind the cloud front and also between stripes. The spacing
      between stripes underwent changes with time as stripes migrated towards and away
      from the cloud front. The global pattern appeared to be stretched by the
      advancing cloud front. At a time corresponding to approximately two cell
      doublings after pattern formation, the pattern decayed, suggesting that there is
      a maximum number of cells that can be maintained within the pattern. Stripes
      appear to consist of high concentrations of cells organized in sinking columns
      that are part of a bioconvection system. Their behavior reveals an interplay
      between bacterial swimming, bioconvection-driven fluid motion, and cell
      concentration. A mathematical model that reproduces the development and dynamics
      of the stripe pattern has been developed.

PMID- 9642179
TI  - Transcriptional analysis of essential genes of the Escherichia coli fatty acid
      biosynthesis gene cluster by functional replacement with the analogous Salmonella
      typhimurium gene cluster.
AB  - The genes encoding several key fatty acid biosynthetic enzymes (called the fab
      cluster) are clustered in the order plsX-fabH-fabD-fabG-acpP-fabF at min 24 of
      the Escherichia coli chromosome. A difficulty in analysis of the fab cluster by
      the polar allele duplication approach (Y. Zhang and J. E. Cronan, Jr., J.
      Bacteriol. 178:3614-3620, 1996) is that several of these genes are essential for
      the growth of E. coli. We overcame this complication by use of the fab gene
      cluster of Salmonella typhimurium, a close relative of E. coli, to provide
      functions necessary for growth. The S. typhimurium fab cluster was isolated by
      complementation of an E. coli fabD mutant and was found to encode proteins with >
      94% homology to those of E. coli. However, the S. typhimurium sequences cannot
      recombine with the E. coli sequences required to direct polar allele duplication
      via homologous recombination. Using this approach, we found that although
      approximately 60% of the plsX transcripts initiate at promoters located far
      upstream and include the upstream rpmF ribosomal protein gene, a promoter located
      upstream of the plsX coding sequence (probably within the upstream gene, rpmF) is
      sufficient for normal growth. We have also found that the fabG gene is
      obligatorily cotranscribed with upstream genes. Insertion of a transcription
      terminator cassette (omega-Cm cassette) between the fabD and fabG genes of the E.
      coli chromosome abolished fabG transcription and blocked cell growth, thus
      providing the first indication that fabG is an essential gene. Insertion of the
      omega-Cm cassette between fabH and fabD caused greatly decreased transcription of
      the fabD and fabG genes and slower cellular growth, indicating that fabD has only
      a weak promoter(s).

PMID- 9642180
TI  - Anaerobic regulation of Bacillus subtilis Krebs cycle genes.
AB  - Krebs cycle enzyme activity in Bacillus subtilis was examined under aerobic and
      anaerobic conditions. Citrate synthase and aconitase activities in cells grown
      anaerobically in the presence of nitrate were reduced by as much as 10- and 30
      fold, respectively, from levels observed under aerobic culture conditions. The
      maximum level of isocitrate dehydrogenase activity during anaerobic growth was
      only twofold lower than that in aerobic cultures. These reductions in activity
      under conditions of anaerobiosis were found to be primarily the result of reduced
      Krebs cycle gene transcription. This repression was not dependent on either the
      fnr or resDE gene products, which have been shown to regulate expression of other
      B. subtilis genes in response to anaerobic conditions. Additionally, catabolite
      control proteins CcpA and CcpB were not responsible for the repression. A dyad
      symmetry element located between positions -73 and -59 relative to the
      transcription start site of the aconitase gene (citB) promoter was previously
      shown to be a target of catabolite repression and the binding site for a putative
      negative regulator during aerobic growth. The deletion of the upstream arm of the
      dyad symmetry region abolished the citB repression observed during anaerobic
      growth. Furthermore, neither citZ or citB was repressed in an anaerobically grown
      citB mutant, an effect that was very likely the result of citrate accumulation.
      These results suggest that catabolite repression and anaerobic repression of citZ
      and citB are regulated by a common mechanism that does not involve CcpA, CcpB,
      Fnr, or ResDE.

PMID- 9642181
TI  - Purification and properties of the F1F0 ATPase of Ilyobacter tartaricus, a sodium
      ion pump.
AB  - The ATPase of Ilyobacter tartaricus was solubilized from the bacterial membranes
      and purified. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the
      purified enzyme revealed the usual subunit pattern of a bacterial F1F0 ATPase.
      The polypeptides with apparent molecular masses of 56, 52, 35, 16.5, and 6.5 kDa
      were identified as the alpha, beta, gamma, epsilon, and c subunits, respectively,
      by N-terminal protein sequencing and comparison with the sequences of the
      corresponding subunits from the Na(+)-translocating ATPase of Propionigenium
      modestum. Two overlapping sequences were obtained for the polypeptides moving
      with an apparent molecular mass of 22 kDa (tentatively assigned as b and delta
      subunits). No sequence could be determined for the putative a subunit (apparent
      molecular mass, 25 kDa). The c subunits formed a strong aggregate with the
      apparent molecular mass of 50 kDa which required treatment with trichloroacetic
      acid for dissociation. The ATPase was inhibited by dicyclohexyl carbodiimide, and
      Na+ ions protected the enzyme from this inhibition. The ATPase was specifically
      activated by Na+ or Li+ ions, markedly at high pH. After reconstitution into
      proteoliposomes, the enzyme catalyzed the ATP-dependent transport of Na+, Li+, or
      Hi+. Proton transport was specifically inhibited by Na+ or Li+ ions, indicating a
      competition between these alkali ions and protons for binding and translocation
      across the membrane. These experiments characterize the I. tartaricus ATPase as a
      new member of the family of FS-ATPases, which use Na+ as the physiological
      coupling ion for ATP synthesis.

PMID- 9642182
TI  - Gene replacement analysis of the Streptomyces virginiae barA gene encoding the
      butyrolactone autoregulator receptor reveals that BarA acts as a repressor in
      virginiamycin biosynthesis.
AB  - Virginiae butanolides (VBs), which are among the butyrolactone autoregulators of
      Streptomyces species, act as a primary signal in Streptomyces virginiae to
      trigger virginiamycin biosynthesis and possess a specific binding protein, BarA.
      To clarify the in vivo function of BarA in the VB-mediated signal pathway that
      leads to virginiamycin biosynthesis, two barA mutant strains (strains NH1 and
      NH2) were created by homologous recombination. In strain NH1, an internal 99-bp
      EcoT14I fragment of barA was deleted, resulting in an in-frame deletion of 33
      amino acid residues, including the second helix of the probable helix-turn-helix
      DNA-binding motif. With the same growth rate as wild-type S. virginiae on both
      solid and liquid media, strain NH1 showed no apparent changes in its
      morphological behavior, indicating that the VB-BarA pathway does not participate
      in morphological control in S. virginiae. In contrast, virginiamycin production
      started 6 h earlier in strain NH1 than in the wild-type strain, demonstrating for
      the first time that BarA is actively engaged in the control of virginiamycin
      production and implying that BarA acts as a repressor in virginiamycin
      biosynthesis. In strain NH2, an internal EcoNI-SmaI fragment of barA was replaced
      with a divergently oriented neomycin resistance gene cassette, resulting in the C
      terminally truncated BarA retaining the intact helix-turn-helix motif. In strain
      NH2 and in a plasmid-integrated strain containing both intact and mutated barA
      genes, virginiamycin production was abolished irrespective of the presence of VB,
      suggesting that the mutated BarA retaining the intact DNA-binding motif was
      dominant over the wild-type BarA. These results further support the hypothesis
      that BarA works as a repressor in virginiamycin production and suggests that the
      helix-turn-helix motif is essential to its function. In strain NH1, VB production
      was also abolished, thus indicating that BarA is a pleiotropic regulatory protein
      controlling not only virginiamycin production but also autoregulator
      biosynthesis.

PMID- 9642183
TI  - Efflux pumps involved in toluene tolerance in Pseudomonas putida DOT-T1E.
AB  - The basic mechanisms underlying solvent tolerance in Pseudomonas putida DOT-T1E
      are efflux pumps that remove the solvent from bacterial cell membranes. The
      solvent-tolerant P. putida DOT-T1E grows in the presence of high concentrations
      (e.g., 1% [vol/vol]) of toluene and octanol. Growth of P. putida DOT-T1E cells in
      LB in the presence of toluene supplied via the gas phase has a clear effect on
      cell survival: the sudden addition of 0.3% (vol/vol) toluene to P. putida DOT-T1E
      pregrown with toluene in the gas phase resulted in survival of almost 100% of the
      initial cell number, whereas only 0.01% of cells pregrown in the absence of
      toluene tolerated exposure to this aromatic hydrocarbon. One class of toluene
      sensitive octanol-tolerant mutant was isolated after Tn5-'phoA mutagenesis of
      wild-type P. putida DOT-T1E cells. The mutant, called P. putida DOT-T1E-18, was
      extremely sensitive to 0.3% (vol/vol) toluene added when cells were pregrown in
      the absence of toluene, whereas pregrowth on toluene supplied via the gas phase
      resulted in survival of about 0.0001% of the initial number. Solvent exclusion
      was tested with 1,2,4-[14C]trichlorobenzene. The levels of radiochemical
      accumulated in wild-type cells grown in the absence and in the presence of
      toluene were not significantly different. In contrast, the mutant was unable to
      remove 1,2,4-[14C]trichlorobenzene from the cell membranes when grown on Luria
      Bertani (LB) medium but was able to remove the aromatic compound when pregrown on
      LB medium with toluene supplied via the gas phase. The amount of 14C-labeled
      substrate in whole cells increased in competition assays in which toluene-and
      xylenes were the unlabeled competitors, whereas this was not the case when
      benzene was the competitor. This finding suggests that the exclusion system works
      specifically with certain aromatic substrates. The mutation in P. putida DOT-T1E
      18 was cloned, and the knockedout gene was sequenced and found to be homologous
      to the drug exclusion gene mexB, which belongs to the efflux pump family of the
      resistant nodulator division type.

PMID- 9642184
TI  - Analysis of genes involved in biosynthesis of coronafacic acid, the polyketide
      component of the phytotoxin coronatine.
AB  - Coronafacic acid (CFA) is the polyketide component of coronatine (COR), a
      phytotoxin produced by the plant-pathogenic bacterium Pseudomonas syringae. The
      genes involved in CFA biosynthesis are encoded by a single transcript which
      encompasses 19 kb of the COR gene cluster. In the present study, the nucleotide
      sequence was determined for a 4-kb region located at the 3' end of the CFA
      biosynthetic gene cluster. Three open reading frames were identified and
      designated cfa8, cfa9, and tnp1; the predicted translation products of these
      genes showed relatedness to oxidoreductases, thioesterases, and transposases,
      respectively. The translational products of cfa8 and cfa9 were overproduced in
      Escherichia coli BL21; however, tnp1 was not translated in these experiments.
      Mutagenesis and complementation analysis indicated that cfa8 is required for the
      production of CFA and COR. Analysis of a cfa9 mutant indicated that this gene is
      dispensable for CFA and COR production but may increase the release of enzyme
      bound products from the COR pathway; tnp1, however, had no obvious function in
      CFA or COR biosynthesis. A genetic strategy was used to produce CFA in a P.
      syringae strain which lacks the COR gene cluster; this approach will be useful in
      future studies designed to investigate biosynthetic products of the CFA gene
      cluster.

PMID- 9642185
TI  - Aeromonas hydrophila adenylyl cyclase 2: a new class of adenylyl cyclases with
      thermophilic properties and sequence similarities to proteins from
      hyperthermophilic archaebacteria.
AB  - Complementation of an Escherichia coli cya mutant with a genomic library from
      Aeromonas hydrophila allowed isolation of clones containing two different cya
      genes. Whereas one of these genes (cyaA) coded for an adenylyl cyclase (AC1)
      belonging to the previously described class I adenylyl cyclases (ACs), the second
      one (cyaB) coded for a protein (AC2) that did not match any previously
      characterized protein when compared to protein sequence databases. In particular,
      it did not align with any of members of the three known classes of ACs. The
      purified AC2 enzyme exhibited remarkable biochemical characteristics, namely, an
      optimum activity at a high temperature (65 degrees C) and at an alkalinic pH
      (9.5). In order to investigate the functions of both cyclases in A. hydrophila,
      each gene was inactivated in the chromosome and the resulting mutant strains were
      examined for physiological alterations. It was shown that, in contrast to cyaA,
      the cyaB gene was not expressed under usual laboratory growth conditions.
      However, introduction of a plasmid harboring the cyaB gene in a cyaA mutant, as
      well as in a cyaA cyaB mutant, allowed cyclic AMP production. AC2 is the first
      member of a new class of previously unrecognized ACs, and to date, no functional
      counterpart has been demonstrated in other organisms. However, scanning databases
      revealed a significant similarity between AC2 and the gene product of three
      hyperthermophilic archaebacteria: Methanobacterium thermoautotrophicum,
      Archaeglobus fulgidus, and Methanococcus jannaschii. The possibility of a gene
      transfer between such phylogenetically divergent bacteria is discussed.

PMID- 9642186
TI  - Induction of the SOS response increases the efficiency of global nucleotide
      excision repair of cyclobutane pyrimidine dimers, but not 6-4 photoproducts, in
      UV-irradiated Escherichia coli.
AB  - Nucleotide excision repair (NER) is responsible for the removal of a variety of
      lesions from damaged DNA and proceeds through two subpathways, global repair and
      transcription-coupled repair. In Escherichia coli, both subpathways require UvrA
      and UvrB, which are induced following DNA damage as part of the SOS response. We
      found that elimination of the SOS response either genetically or by treatment
      with the transcription inhibitor rifampin reduced the efficiency of global repair
      of the major UV-induced lesion, the cyclobutane pyrimidine dimer (CPD), but had
      no effect on the global repair of 6-4 photoproducts. Mutants in which the SOS
      response was constitutively derepressed repaired CPDs more rapidly than did wild
      type cells, and this rate was not affected by rifampin. Transcription-coupled
      repair of CPDs occurred in the absence of SOS induction but was undetectable when
      the response was expressed constitutively. These results suggest that damage
      inducible synthesis of UvrA and UvrB is necessary for efficient repair of CPDs
      and that the levels of these proteins determine the rate of NER of UV
      photoproducts. We compare our findings with recent data from eukaryotic systems
      and suggest that damage-inducible stress responses are generally critical for
      efficient global repair of certain types of genomic damage.

PMID- 9642187
TI  - Mutagenesis and expression of amo, which codes for ammonia monooxygenase in
      Nitrosomonas europaea.
AB  - Nitrosomonas europaea has two copies of the operon encoding ammonia monooxygenase
      (AMO). The nucleotide sequences of the two copies of amoA were obtained, and they
      were found to differ by one nucleotide. To determine if both copies of amoA were
      functional, insertional mutagenesis was performed to inactivate either copy of
      amoA alone. A DNA cassette containing the lacZ and kan genes inserted into amoA
      was constructed. Mutagenesis was done by using transformation and homologous
      recombination to mobilize the cassette into the chromosomal copies of amoA.
      Mutations were obtained in both copies of amoA. Either copy of amoA was
      sufficient to support growth when the other copy was disrupted. However,
      inactivation of one copy of amoA, but not the other, resulted in slower growth.
      Measurements of ammonia-dependent O2 consumption, which depends on AMO, confirmed
      that the slower-growing mutant had lower activity while the faster-growing mutant
      had near wild-type levels of activity. Similarly, as measured by [14C]acetylene
      label incorporation, there was less active AMO present in the slower-growing
      mutant than in the faster-growing mutant or in the wild type. Northern blot
      analysis of transcription likewise showed that the slower-growing mutant had less
      full-sized AMO mRNA.

PMID- 9642188
TI  - Replication terminator protein-based replication fork-arrest systems in various
      Bacillus species.
AB  - The replication terminator protein (RTP) of Bacillus subtilis interacts with its
      cognate DNA terminators to cause replication fork arrest, thereby ensuring that
      the forks approaching one another at the conclusion of a round of replication
      meet within a restricted terminus region. A similar situation exists in
      Escherichia coli, but it appears that the fork-arrest systems in these two
      organisms have evolved independently of one another. In the present work, RTP
      homologs in four species closely related to B. subtilis (B. atrophaeus, B.
      amyloliquefaciens, B. mojavensis, and B. vallismortis) have been identified and
      characterized. An RTP homolog could not be identified in another closely related
      species, B. licheniformis. The nucleotide and amino acid changes from B. subtilis
      among the four homologs are consistent with the recently established phylogenetic
      tree for these species. The GC contents of the rtp genes raise the possibility
      that these organisms arose within this branch of the tree by horizontal transfer
      into a common ancestor after their divergence from B. licheniformis. Only 5 amino
      acid residue positions were changed among the four homologs, despite an up to
      17.2% change in the nucleotide sequence, a finding that highlights the importance
      of the precise folded structure to the functioning of RTP. The absence of any
      significant change in the proposed DNA-binding region of RTP emphasizes the
      importance of its high affinity for the DNA terminator in its functioning. By
      coincidence, the single change (E30K) found in the B. mojavensis RTP corresponds
      exactly to that purposefully introduced by others into B. subtilis RTP to
      implicate a crucial role for E30 in the fork-arrest mechanism. The natural
      occurrence of this variant is difficult to reconcile with such an implication,
      and it was shown directly that RTP.E30K functions normally in fork arrest in B.
      subtilis in vivo. Additional DNA terminators were identified in the new RTP
      homolog-containing strains, allowing the definition of a Bacillus terminator
      consensus and identification of two more terminators in the B. subtilis 168
      genome sequence to bring the total to nine.

PMID- 9642189
TI  - Enantioselective uptake and degradation of the chiral herbicide dichlorprop [(RS)
      2-(2,4-dichlorophenoxy)propanoic acid] by Sphingomonas herbicidovorans MH.
AB  - Sphingomonas herbicidovorans MH was able to completely degrade both enantiomers
      of the chiral herbicide dichlorprop [(RS)-2-(2,4-dichlorophenoxy)propanoic acid],
      with preferential degradation of the (S) enantiomer over the (R) enantiomer.
      These results are in agreement with the recently reported enantioselective
      degradation of mecoprop [(RS)-2-(4-chloro-2-methylphenoxy)propanoic acid] by this
      bacterium (C. Zipper, K. Nickel, W. Angst, and H.-P. E. Kohler, Appl. Environ.
      Microbiol. 62:4318-4322, 1996). Uptake of (R)-dichlorprop, (S)-dichlorporp, and
      2,4-D (2,4-dichlorophenoxyacetic acid) was inducible. Initial uptake rates of
      cells grown on the respective substrate showed substrate saturation kinetics with
      apparent affinity constants (Kt) of 108, 93, and 117 microM and maximal
      velocities (Vmax) of 19, 10, and 21 nmol min-1 mg of protein-1 for (R)
      dichlorprop, (S)-dichlorprop, and 2,4-D, respectively. Transport of (R)
      dichlorprop, (S)-dichlorprop, and 2,4-D was completely inhibited by various
      uncouplers and by nigericin but was only marginally inhibited by valinomycin and
      by the ATPase inhibitor N,N'-dicyclohexylcarbodiimine. Experiments on the
      substrate specificity of the putative transport systems revealed that (R)
      dichlorprop uptake was inhibited by (R)-mecoprop but not by (S)-mecoprop, (S)
      dichlorprop, or 2,4-D. On the other hand, the (S)-dichlorprop transport was
      inhibited by (S)-mecoprop but not by (R)-mecoprop, (R)-dichlorprop, or 2,4-D.
      These results provide evidence that the first step in the degradation of
      dichlorprop, mecoprop, and 2,4-D by S. herbicidovorans is active transport and
      that three inducible, proton gradient-driven uptake systems exist: one for (R)
      dichlorprop and (R)-mecoprop, another for (S)-dichlorprop and (S)-mecoprop, and a
      third for 2,4-D.

PMID- 9642190
TI  - Regulation of switching frequency and bias of the bacterial flagellar motor by
      CheY and fumarate.
AB  - The effect of CheY and fumarate on switching frequency and rotational bias of the
      bacterial flagellar motor was analyzed by computer-aided tracking of tethered
      Escherichia coli. Plots of cells overexpressing CheY in a gutted background
      showed a bell-shaped correlation curve of Switching frequency and bias centering
      at about 50% clockwise rotation. Gutted cells (i.e., with cheA to cheZ deleted)
      with a low CheY level but a high cytoplasmic fumarate concentration displayed the
      same correlation of switching frequency and bias as cells overexpressing CheY at
      the wild-type fumarate level. Hence, a high fumarate level can phenotypically
      mimic CheY overexpression by simultaneously changing the switching frequency and
      the bias. A linear correlation of cytoplasmic fumarate concentration and
      clockwise rotation bias was found and predicts exclusively counter-clockwise
      rotation without switching when fumarate is absent. This suggests that (i)
      fumarate is essential for clockwise rotation in vivo and (ii) any metabolically
      induced fluctuation of its cytoplasmic concentration will result in a transient
      change in bias and switching probability. A high fumarate level resulted in a
      dose-response curve linking bias and cytoplasmic CheY concentration that was
      offset but with a slope similar to that for a low fumarate level. It is concluded
      that fumarate and CheY act additively presumably at different reaction steps in
      the conformational transition of the switch complex from counterclockwise to
      clockwise motor rotation.

PMID- 9642191
TI  - Sed1p is a major cell wall protein of Saccharomyces cerevisiae in the stationary
      phase and is involved in lytic enzyme resistance.
AB  - A 260-kDa structural cell wall protein was purified from sodium dodecyl sulfate
      treated cell walls of Saccharomyces cerevisiae by incubation with Rarobacter
      faecitabidus protease I, which is a yeast-lytic enzyme. Amino acid sequence
      analysis revealed that this protein is the product of the SED1 gene. SED1 was
      formerly identified as a multicopy suppressor of erd2, which encodes a protein
      involved in retrieval of luminal endoplasmic reticulum proteins from the
      secretory pathway. Sed1p is very rich in threonine and serine and, like other
      structural cell wall proteins, contains a putative signal sequence for the
      addition of a glycosylphosphatidylinositol anchor. However, the fact that Sed1p,
      unlike other cell wall proteins, has six cysteines and seven putative N
      glycosylation sites suggests that Sed1p belongs to a new family of cell wall
      proteins. Epitope-tagged Sed1p was detected in a beta-1,3-glucanase extract of
      cell walls by immunoblot analysis, suggesting that Sed1p is a glucanase
      extractable cell wall protein. The expression of Sed1p mRNa increased in the
      stationary phase and was accompanied by an increase in the Sed1p content of cell
      walls. Disruption of SED1 had no effect on exponentially growing cells but made
      stationary-phase cells sensitive to Zymolyase. These results indicate that Sed1p
      is a major structural cell wall protein in stationary-phase cells and is required
      for lytic enzyme resistance.

PMID- 9642192
TI  - Identification and characterization of two quiescent porin genes, nmpC and ompN,
      in Escherichia coli BE.
AB  - The genomic DNA of the BE strain of Escherichia coli has been scrutinized to
      detect porin genes that have not been identified so far. Southern blot analysis
      yielded two DNA segments which proved highly homologous to, yet distinct from,
      the ompC, ompF, and phoE porin genes. The two genes were cloned and sequenced.
      One of them, designated ompN, encodes a porin which, due to low levels of
      expression, has eluded prior identification. The functional properties (single
      channel conductance) of the OmpN porin, purified to homogeneity, closely resemble
      those of the OmpC porin from E. coli K-12. The second DNA fragment detected
      corresponds to the nmpC gene, which, due to an insertion of an IS1 element in its
      coding region, is not expressed in E. coli BE.

PMID- 9642193
TI  - Identification of a specific chaperone for SptP, a substrate of the centisome 63
      type III secretion system of Salmonella typhimurium.
AB  - Salmonella typhimurium uses of a type III protein secretion system encoded at
      centisome 63 of its chromosome to deliver effector molecule into the host cell.
      These proteins stimulate host cell responses such as reorganization of the actin
      cytoskeleton and activation of transcription factors. One of these effector
      proteins is SptP, a tyrosine phosphatase that causes disruption of the host cell
      actin cytoskeleton. A characteristic feature of many substrates of type III
      secretion systems is their association with specific cytoplasmic chaperones which
      appears to be required for secretion and/or translocation of these proteins into
      the host cell. We report here the identification of SicP, a 13-kDa acidic
      polypeptide that is encoded immediately upstream of sptP. A loss-of-function
      mutation in sicP resulted in drastically reduced levels of SptP but did not
      affect sptP expression, indicating that SicP exerts its effect
      posttranscriptionally. Pulse-chase experiments demonstrated that the loss of SicP
      leads to increased degradation of SptP. In addition, we show that SicP binds to
      SptP directly and that the binding site is located between residues 15 and 100 of
      the tyrosine phosphatase. Taken together, these results indicate that SicP acts
      as a specific chaperone for SptP.

PMID- 9642194
TI  - Expression of the bglH gene of Lactobacillus plantarum is controlled by carbon
      catabolite repression.
AB  - A newly identified bglH gene coding for a phospho-beta-glucosidase of
      Lactobacillus plantarum was isolated and expressed in Escherichia coli. The
      sequence analysis of the cloned DNA fragment showed an open reading frame
      encoding a 480-amino-acid protein with a calculated molecular mass of 53 kDa. The
      bglH gene was shown to be expressed on a monocistronic transcriptional unit. Its
      transcription was repressed 10-fold in L. plantarum cells grown on glucose
      compared to the beta-glucoside salicin as a sole carbon source. A catabolite
      responsive element (CRE) spanning from -3 to +11 with respect to the
      transcriptional start point was found, and its functionality was assessed by
      mutational analysis. In vitro and in vivo DNA binding experiments suggested the
      occurrence of a DNA-protein complex at the CRE site, which would mediate glucose
      repression of bglH expression.

PMID- 9642195
TI  - Genetic recombination in Bacillus subtilis 168: effects of recU and recS
      mutations on DNA repair and homologous recombination.
AB  - Bacillus subtilis recombination-deficient mutants were constructed by inserting a
      selectable marker (cat gene) into the yppB and ypbC coding regions. The yppB:cat
      and ypbC:cat null alleles rendered cells sensitive to DNA-damaging agents,
      impaired plasmid transformation (25- and 100-fold), and moderately affected
      chromosomal transformation when present in an otherwise Rec+ B. subtilis strain.
      The yppB gene complemented the defect of the recG40 strain. yppB and ypbC and
      their respective null alleles were termed "recU" and "recU1" (recU:cat) and
      "recS" and "recS1" (recS:cat), respectively. The recU and recS mutations were
      introduced into rec-deficient strains representative of the alpha (recF), beta
      (addA5 addB72), gamma (recH342), and epsilon (recG40) epistatic groups. The recU
      mutation did not modify the sensitivity of recH cells to DNA-damaging agents, but
      it did affect inter- and intramolecular recombination in recH cells. The recS
      mutation did not modify the sensitivity of addAB cells to DNA-damaging agents,
      and it marginally affected recF, recH, and recU cells. The recS mutation markedly
      reduced (about 250-fold) intermolecular recombination in recH cells, and there
      were reductions of 10- to 20-fold in recF, addAB, and recU cells. Intramolecular
      recombination was blocked in recS recF, recS addAB, and recS recU cells. RecU and
      RecS have no functional counterparts in Escherichia coli. Altogether, these data
      indicate that the recU and recS proteins are required for DNA repair and
      intramolecular recombination and that the recF (alpha epistatic group), addAB
      (beta), recH (gamma), recU (epsilon), and recS genes provide overlapping
      activities that compensate for the effects of single mutation. We tentatively
      placed recS within a new group, termed "zeta".

PMID- 9642196
TI  - The V antigen of Yersinia pestis regulates Yop vectorial targeting as well as Yop
      secretion through effects on YopB and LcrG.
AB  - Yersinia pestis expresses a set of secreted proteins called Yops and the
      bifunctional LcrV, which has both regulatory and antihost functions. Yops and
      LcrV expression and the activity of the type III mechanism for their secretion
      are coordinately regulated by environmental signals such as Ca2+ concentration
      and eukaryotic cell contact. In vitro, Yops and LcrV are secreted into the
      culture medium in the absence of Ca2+ as part of the low-Ca2+ response (LCR). The
      LCR is induced in a tissue culture model by contact with eukaryotic cells that
      results in Yop translocation into cells and subsequent cytotoxicity. The
      secretion mechanism is believed to indirectly regulate expression of lcrV and yop
      operons by controlling the intracellular concentration of a secreted negative
      regulator. LcrG, a secretion-regulatory protein, is thought to block secretion of
      Yops and LcrV, possibly at the inner face of the inner membrane. A recent model
      proposes that when the LCR is induced, the increased expression of LcrV yields an
      excess of LcrV relative to LcrG, and this is sufficient for LcrV to bind LcrG and
      unblock secretion. To test this LcrG titration model, LcrG and LcrV were
      expressed alone or together in a newly constructed lcrG deletion strain, a delta
      lcrG2 mutant, of Y. pestis that produces low levels of LcrV and constitutively
      expresses and secretes Yops. Overexpression of LcrG in this mutant background was
      able to block secretion and depress expression of Yops in the presence of Ca2+
      and to dramatically decrease Yop expression and secretion in growth medium
      lacking Ca2+. Overexpression of both LcrG and LcrV in the delta lcrG2 strain
      restored wild-type levels of Yop expression and Ca2+ control of Yop secretion.
      Surprisingly, when HeLa cells were infected with the delta lcrG2 strain, no
      cytotoxicity was apparent and translocation of Yops was abolished. This
      correlated with an altered distribution of YopB as measured by accessibility to
      trypsin. These effects were not due to the absence of LcrG, because they were
      alleviated by restoration of LcrV expression and secretion alone. LcrV itself was
      found to enter HeLa cells in a nonpolarized manner. These studies supported the
      LcrG titration model of LcrV's regulatory effect at the level of Yop secretion
      and revealed a further role of LcrV in the deployment of YopB, which in turn is
      essential for the vectorial translocation of Yops into eukaryotic cells.

PMID- 9642197
TI  - Cloning, sequencing, and phenotypic characterization of the rpoS gene from
      Pseudomonas putida KT2440.
AB  - A gene homologous to the rpoS gene of Escherichia coli was cloned from a
      Pseudomonas putida KT2440 gene bank by complementation of the rpoS-deficient
      strain E. coli ZK918. The rpoS gene of P. putida complemented the acid
      sensitivity and catalase deficiency of the rpoS mutant of E. coli and stimulated
      expression of the RpoS-controlled promoter, bolAp1. The gene was sequenced and
      found to be highly similar to the rpoS genes of other gram-negative bacteria.
      Like in other gram-negative bacteria, a homolog of the nlpD gene was found
      upstream to the rpoS gene. A transcriptional fusion of the promoter of the P.
      putida rpoS gene to the luxAB genes from Vibrio harveyi was constructed and used
      as an inactivated allele of rpoS for gene replacement of the wild-type copy in
      the chromosome of P. putida. The resultant rpoS mutant of P.putida, C1R1, showed
      reduced survival of carbon starvation and reduced cross-protection against other
      types of stress in cells starved for carbon, in particular after a challenge with
      ethanol. Survival in soil amended with m-methylbenzoate was also reduced in the
      mutant strain P. putida C1R1. The RpoS protein of P. putida controls the
      expression of more than 50 peptides, which are normally expressed in cells after
      a short period of carbon starvation.

PMID- 9642198
TI  - Clustered genes encoding the methyltransferases of methanogenesis from
      monomethylamine.
AB  - Coenzyme M (CoM) is methylated during methanogenesis from monomethyamine in a
      reaction catalyzed by three proteins. Using monomethylamine, a 52-kDa polypeptide
      termed monomethylamine methyltransferase (MMAMT) methylates the corrinoid
      cofactor bound to a second polypeptide, monomethylamine corrinoid protein (MMCP).
      Methylated MMCP then serves as a substrate for MT2-A, which methylates CoM. The
      genes for these proteins are clustered on 6.8 kb of DNA in Methanosarcina barkeri
      MS. The gene encoding MMCP (mtmC) is located directly upstream of the gene
      encoding MMAMT (mtmB). The gene encoding MT2-A (mtbA) was found 1.1 kb upstream
      of mtmC, but no obvious open reading frame was found in the intergenic region
      between mtbA and mtmC. A single monocistronic transcript was found for mtbA that
      initiated 76 bp from the translational start. Separate transcripts of 2.4 and 4.7
      kb were detected, both of which carried mtmCB. The larger transcript also encoded
      mtmP, which is homologous to the APC family of cationic amine permeases and may
      therefore encode a methylamine permease. A single transcriptional start site was
      found 447 bp upstream of the translational start of mtmC. MtmC possesses the
      corrinoid binding motif found in corrinoid proteins involved in dimethylsulfide-
      and methanol-dependent methanogenesis, as well as in methionine synthase. The
      open reading frame of mtmB was interrupted by a single in-frame, midframe, UAG
      codon which was also found in mtmB from M. barkeri NIH. A mechanism that
      circumvents UAG-directed termination of translation must operate during
      expression of mtmB in this methanogen.

PMID- 9642199
TI  - Membrane-bound lytic endotransglycosylase in Escherichia coli.
AB  - The gene for a novel endotype membrane-bound lytic transglycosylase, emtA, was
      mapped at 26.7 min of the E. coli chromosome. EmtA is a lipoprotein with an
      apparent molecular mass of 22kDa. Overexpression of the emtA gene did not result
      in bacteriolysis in vivo, but the enzyme was shown to hydrolyze glycan strands
      isolated from murein by amidase treatment. The formation of tetra- and
      hexasaccharides, but no disaccharides, reflects the endospecificity of the
      enzyme. The products are characterized by the presence of 1,6-anhydromuramic
      acid, indicating a lytic transglycosylase reaction mechanism. EmtA may function
      as a formatting enzyme that trims the nascent murein strands produced by the
      murein synthesis machinery into proper sizes, or it may be involved in the
      formation of tightly controlled minor holes in the murein sacculus to facilitate
      the export of bulky compounds across the murein barrier.

PMID- 9642200
TI  - The A1A0 ATPase from Methanosarcina mazei: cloning of the 5' end of the aha
      operon encoding the membrane domain and expression of the proteolipid in a
      membrane-bound form in Escherichia coli.
AB  - Three additional ATPase genes, clustered in the order ahaH, ahaI, and ahaK, were
      found upstream of the previously characterized genes ahaECFABDG coding for the
      archaeal A1A0 ATPase from Methanosarcina mazei. ahaH, the first gene in the
      cluster, is preceded by a conserved promoter sequence. Northern blot analysis
      revealed that the clusters ahaHIK and ahaECFABDG are transcribed as one message.
      AhaH is a hydrophilic polypeptide and is similar to peptides of previously
      unassigned function encoded by genes preceding postulated ATPase genes in
      Methanobacterium thermoautotrophicum and Methanococcus jannaschii. AhaI has a two
      domain structure with a hydrophilic domain of 39 kDa and a hydrophobic domain
      with seven predicted transmembrane alpha helices. It is similar to the 100-kDa
      polypeptide of V1V0 ATPases and is therefore suggested to participate in proton
      transport. AhaK is a hydrophobic polypeptide with two predicted transmembrane
      alpha helices and, on the basis of sequence comparisons and immunological
      studies, is identified as the proteolipid, a polypeptide which is essential for
      proton translocation. However, it is only one-half and one-third the size of the
      proteolipids from M. thermoautotrophicum and M. jannaschii, respectively. ahaK is
      expressed in Escherichia coli, and it is incorporated into the cytoplasmic
      membrane despite the different chemical natures of lipids from archaea and
      bacteria. This is the first report on the expression and incorporation into E.
      coli lipids of a membrane integral enzyme from a methanogens, which will
      facilitate analysis of the structure and function of the membrane domain of the
      methanoarchaeal ATPase.

PMID- 9642201
TI  - Evolution of cyanobacteria by exchange of genetic material among phyletically
      related strains.
AB  - The cyanobacterial radiation consists of several lineages of phyletically
      (morphologically and genetically) related organisms. Several of these organisms
      show a striking resemblance to fossil counterparts. To investigate the molecular
      mechanisms responsible for stabilizing or homogenizing cyanobacterial characters,
      we compared the evolutionary rates and phylogenetic origins of the small-subunit
      rRNA-encoding DNA (16S rDNA), the conserved gene rbcL (encoding D-ribulose 1,5
      bisphosphate carboxylase-oxygenase large subunit), and the less conserved gene
      rbcX. This survey includes four categories of phyletically related organisms: 16
      strains of Microcystis, 6 strains of Tychonema, 10 strains of Planktothrix, and
      12 strains of Nostoc. Both rbcL and rbcX can be regarded as neutrally evolving
      genes, with 95 to 100% and 50 to 80% synonymous nucleotide substitutions,
      respectively. There is generally low sequence divergence within the Microcystis,
      Tychonema, and Planktothrix categories both for rbcLX and 16S rDNA. The Nostoc
      category, on the other hand, consists of three genetically clustered lineages for
      these loci. The 16S rDNA and rbcLX phylogenies are not congruent for strains
      within the clustered groups. Furthermore, analysis of the phyletic structure for
      rbcLX indicates recombinational events between the informative sites within this
      locus. Thus, our results are best explained by a model involving both intergenic
      and intragenic recombinations. This evolutionary model explains the DNA sequence
      clustering for the modern species as a result of sequence homogenization
      (concerted evolution) caused by exchange of genetic material for neutrally
      evolving genes. The morphological clustering, on the other hand, is explained by
      structural and functional stability of these characters. We also suggest that
      exchange of genetic material for neutrally evolving genes may explain the
      apparent stability of cyanobacterial morphological characters, perhaps over
      billions of years.

PMID- 9642202
TI  - Does disparate occurrence of autoregulatory programmed frameshifting in decoding
      the release factor 2 gene reflect an ancient origin with loss in independent
      lineages?
AB  - In Escherichia coli an autoregulatory mechanism of programmed ribosomal
      frameshifting governs the level of polypeptide chain release factor 2. From an
      analysis of 20 sequences of genes encoding release factor 2, we infer that this
      frameshift mechanism was present in a common ancestor of a large group of
      bacteria and has subsequently been lost in three independent lineages.

PMID- 9642203
TI  - Secretion of elastinolytic enzymes and their propeptides by Pseudomonas
      aeruginosa.
AB  - Elastase of Pseudomonas aeruginosa is synthesized as a preproenzyme. The signal
      sequence is cleaved off during transport across the inner membrane and, in the
      periplasm, proelastase is further processed. We demonstrate that the propeptide
      and the mature elastase are both secreted but that the propeptide is degraded
      extracellularly. In addition, reduction of the extracellular proteolytic activity
      led to the accumulation of unprocessed forms of LasA and LasD in the
      extracellular medium, which shows that these enzymes are secreted in association
      with their propeptides. Furthermore, a hitherto undefined protein with homology
      to a Streptomyces griseus aminopeptidase accumulated under these conditions.

PMID- 9642204
TI  - tetA(L) mutants of a tetracycline-sensitive strain of Bacillus subtilis with the
      polynucleotide phosphorylase gene deleted.
AB  - A Bacillus subtilis strain with the polynucleotide phosphorylase gene deleted was
      sensitive for growth in the presence of tetracycline. This strain was used to
      select for tetracycline-resistant mutants. A point mutation in the tetA(L)
      promoter and a spontaneously occurring tetA(L) gene copy number mutant were
      characterized.

PMID- 9642205
TI  - Identification of the repressor-encoding gene of the Lactobacillus bacteriophage
      A2.
AB  - The repressor gene of the Lactobacillus phage A2 has the following properties: it
      (i) encodes a 224-residue polypeptide with DNA binding and RecA cleavage motifs,
      (ii) is expressed in lysogenic cultures, and (iii) confers superinfection
      immunity on the host. Adjacent, but divergently transcribed, lies another open
      reading frame whose product resembles the lambda Cro protein. In the 161-bp
      intergenic segment, putative promoters and operators have been detected.

PMID- 9642206
TI  - Characterization of the earliest known Staphylococcus aureus plasmid encoding a
      multidrug efflux system.
AB  - The staphylococcal qacB-encoding multidrug resistance plasmid pSK156, isolated
      from a clinical strain dating from 1951, was characterized. Comparison of the
      regions flanking qacB with other qacA- and qacB-encoding plasmids provided
      insights into the evolution and dissemination of these multidrug efflux genes and
      led to the detection of the earliest known copy of the insertion sequence IS257.

PMID- 9642207
TI  - Mutants of Citrobacter freundii that transport and utilize melibiose.
AB  - We have isolated mutants of Citrobacter freundii that can grow on melibiose.
      Inducible alpha-galactosidase activity and melibiose transport activity were
      detected in the mutant cells but not in the wild-type cells. We detected a DNA
      region which hybridized with melB (the gene for the melibiose transporter) DNA of
      Escherichia coli in the chromosomal DNA of wild-type C. freundii. Protons, but
      not sodium ions, were found to be the coupling cations for melibiose (and methyl
      beta-D-thiogalactoside) transport in the mutant cells.

PMID- 9642208
TI  - The fnr gene of Bacillus licheniformis and the cysteine ligands of the C-terminal
      FeS cluster.
AB  - In the facultatively anaerobic bacterium Bacillus licheniformis a gene encoding a
      protein of the fumarate nitrate reductase family of transcriptional regulators
      (Fnr) was isolated. Unlike Fnr proteins from gram-negative bacteria, but like Fnr
      from Bacillus subtilis, the protein contained a C-terminal cluster of cysteine
      residues. Unlike in Fnr from B. subtilis, this cluster (Cys226-X2-Cys229-X4
      Cys234) is composed of only three Cys residues, which are supposed to serve
      together with an internal residue (Cys71) as the ligands for an FeS center.
      Transfer of the B. licheniformis gene to an fnr mutant of B. subtilis
      complemented the ability for synthesis of nitrate reductase during anaerobic
      growth.

PMID- 9642210
TI  - KtrAB, a new type of bacterial K(+)-uptake system from Vibrio alginolyticus.
AB  - Vibrio alginolyticus contained two adjacent genes, ktrA and ktrB, which encode a
      new type of bacterial K(+)-uptake system. KtrA and KtrB are peripheral and
      integral membrane proteins, respectively. Six of the nine sequenced bacterial
      genomes contain homologs to both ktrA and ktrB, suggesting that KtrAB is
      widespread.

PMID- 9642209
TI  - Aberrant cell division and random FtsZ ring positioning in Escherichia coli cpxA*
      mutants.
AB  - In Escherichia coli, certain mutations in the cpxA gene (encoding a sensor kinase
      of a two-component signal transduction system) randomize the location of FtsZ
      ring assembly and dramatically affect cell division. However, deletion of the
      cpxRA operon, encoding the sensor kinase and its cognate regulator CpxR, has no
      effect on division site biogenesis. It appears that certain mutant sensor kinases
      (CpxA*) either exhibit hyperactivity on CpxR or extend their signalling activity
      to one or more noncognate response regulators involved in cell division.

PMID- 9642211
TI  - Mechanism of action of human P-glycoprotein ATPase activity. Photochemical
      cleavage during a catalytic transition state using orthovanadate reveals cross
      talk between the two ATP sites.
AB  - Human P-glycoprotein (P-gp), an ATP-dependent efflux pump responsible for cross
      resistance of human cancers to a variety of lipophilic compounds, is composed of
      two homologous halves, each containing six transmembrane domains and an ATP
      binding/utilization domain. To determine whether each site can hydrolyze ATP
      simultaneously, we used an orthovanadate (Vi)-induced ADP-trapping technique (P
      gp.MgADP.Vi). In analogy with other ATPases, a photochemical peptide bond
      cleavage reaction occurs within the Walker A nucleotide binding domain consensus
      sequence (GX4GK(T/S)) when the molecule is trapped with Vi in an inhibited
      catalytic transition state (P-gp.MgADP.Vi) and incubated in the presence of
      ultraviolet light. Upon reconstitution into proteoliposomes, histidine-tagged
      purified P-gp from baculovirus-infected insect cells had drug-stimulated ATPase
      activity. Reconstituted P-gp was incubated with either ATP or 8-azido-ATP in the
      presence or absence of Vi under ultraviolet (365 nm) light on ice for 60 min. The
      resultant products were separated by SDS-polyacrylamide gel electrophoresis and
      subjected to immunoblotting with seven different human P-gp-specific antibodies
      covering the entire length of the molecule. Little to no degradation of P-gp was
      observed in the absence of Vi. In the presence of Vi, products of approximately
      28, 47, 94, and 110 kDa were obtained, consistent with predicted molecular
      weights from cleavage at either of the ATP sites but not both sites. An
      additional Vi-dependent cleavage site was detected at or near the trypsin site in
      the linker region of P-gp. These results suggest that both the amino- and
      carboxyl-terminal ATP sites can hydrolyze ATP. However, there is no evidence that
      ATP can be hydrolyzed simultaneously by both sites.

PMID- 9642212
TI  - A role for phospholipase D (Pld1p) in growth, secretion, and regulation of
      membrane lipid synthesis in yeast.
AB  - The SEC14 gene encodes a phosphatidylinositol/phosphatidylcholine transfer
      protein essential for secretion and growth in yeast (1). Mutations (cki1, cct1,
      and cpt1) in the CDP-choline pathway for phosphatidylcholine synthesis suppress
      the sec14 growth defect (2), permitting sec14(ts) cki1, sec14(ts) cct1, and
      sec14(ts) cpt1 strains to grow at the sec14(ts) restrictive temperature.
      Previously, we reported that these double mutant strains also excrete the
      phospholipid metabolites, choline and inositol (3). We now report that these
      choline and inositol excretion phenotypes are eliminated when the SPO14 (PLD1)
      gene encoding phospholipase D1 is deleted. In contrast to sec14(ts) cki1 strains,
      sec14(ts) cki1 pld1 strains are not viable at the sec14(ts) restrictive
      temperature and exhibit a pattern of invertase secretion comparable with
      sec14(ts) strains. Thus, the PLD1 gene product appears to play an essential role
      in the suppression of the sec14(ts) defect by CDP-choline pathway mutations,
      indicating a role for phospholipase D1 in growth and secretion. Furthermore,
      sec14(ts) strains exhibit elevated Ca2+-independent, phophatidylinositol 4,5
      bisphosphate-stimulated phospholipase D activity. We also propose that
      phospholipase D1-mediated phosphatidylcholine turnover generates a signal that
      activates transcription of INO1, the structural gene for inositol 1-phosphate
      synthase.

PMID- 9642213
TI  - High-affinity binding of epidermal growth factor (EGF) to EGF receptor is
      disrupted by overexpression of mutant dynamin (K44A).
AB  - Activation of the epidermal growth factor receptor (EGFR) kinase was analyzed in
      cells conditionally defective for clathrin-dependent endocytosis by
      overexpression of mutant dynamin (K44A). EGF-induced autophosphorylation of the
      EGFR on ice was strongly reduced in cells overexpressing mutant dynamin, and
      consistently, binding analyses showed that high-affinity EGFRs were lost. In the
      absence of mutant dynamin the cells displayed both high- and low-affinity EGFR.
      At 4 degreesC EGF-EGFR localized mainly outside coated pits regardless of
      expression of mutant dynamin. However, also low-affinity EGFR efficiently moved
      to coated pits upon incubating cells at 37 degreesC. Thus, expression of mutant
      dynamin disrupts high-affinity binding of EGF, but not ligand-induced recruitment
      of EGFR to clathrin-coated pits.

PMID- 9642214
TI  - A common requirement for the catalytic activity and both SH2 domains of SHP-2 in
      mitogen-activated protein (MAP) kinase activation by the ErbB family of
      receptors. A specific role for SHP-2 in map, but not c-Jun amino-terminal kinase
      activation.
AB  - The ErbB family of receptors, which include the epidermal growth factor receptor
      (EGFR), ErbB2, ErbB3, and ErbB4 mediate the actions of a family of bioactive
      polypeptides. EGF signals through EGFR, whereas heregulin (HRG) signaling is
      initiated through binding to either ErbB3 or ErbB4. In this report we studied the
      role of protein-tyrosine phosphatase SHP-2 in ErbB-mediated activation of mitogen
      activated protein kinase (MAPK) by overexpressing SHP-2 mutants in COS-7 cells.
      We demonstrate that enzymatic activity and both NH2- and COOH-terminal SH2
      domains of SHP-2 are required for EGF-induced MAPK activation, but not for c-Jun
      amino-terminal kinase stimulation or MAPK activation which occurred in response
      to myristoylated son of sevenless, activated Ras, or phorbol ester. Dominant
      negative forms of SHP-2 had no effect on EGF-stimulated interaction of GRB2 with
      EGFR or SHC, nor did they influence phosphorylation of SHC and SHC/EGFR
      association. The same mutant SHP-2 structures that inhibited EGF-mediated
      stimulation of MAPK also blocked HRG alpha/beta-induced MAPK activation. EGF or
      HRG beta caused SHP-2 SH2 domains to engage multiple phosphotyrosine proteins,
      and mutation of either domain disrupted these associations. These results
      demonstrate that SHP-2 performs a common and essential function(s) in ligand
      stimulated MAPK activation by the ErbB family of receptors.

PMID- 9642215
TI  - Abrogation of mitochondrial cytochrome c release and caspase-3 activation in
      acquired multidrug resistance.
AB  - Acquired multidrug resistance to anti-cancer agents has been associated with
      overexpression of the P-glycoprotein and other members of the ATP-binding
      cassette superfamily. The present studies demonstrate that SCC-25 cells selected
      for resistance to the alkylating agent cisplatin (CDDP) overexpress the anti
      apoptotic Bcl-xL protein. In contrast to parental cells, the SCC-25/CDDP
      resistant variant failed to exhibit activation of caspase-3, cleavage of protein
      kinase C delta, and other characteristics of apoptosis in response to CDDP.
      Similar results were obtained when SCC-25/CDDP cells were exposed to the
      structurally and functionally unrelated antimetabolite 1-beta-D-arabinofuranosyl
      cytosine (ara-C). Other cells selected for resistance to doxorubicin or
      vincristine also exhibited overexpression of Bcl-xL and failed to respond to CDDP
      and ara-C with activation of caspase-3. The results further demonstrate that
      multidrug-resistant cells exhibit a block in the release of mitochondrial
      cytochrome c into the cytosol and that this effect is dependent on overexpression
      of Bcl-xL. The demonstration that lysates from the resistant cells respond to the
      addition of cytochrome c with activation of caspase-3 confirms that the block in
      apoptosis is because of inhibition of mitochondrial cytochrome c release. These
      findings demonstrate that cells respond to diverse classes of anti-cancer drugs
      with overexpression of Bcl-xL and that this response represents another mechanism
      of acquired multidrug resistance.

PMID- 9642216
TI  - Steroid receptor coactivator-1 coactivates activating protein-1-mediated
      transactivations through interaction with the c-Jun and c-Fos subunits.
AB  - Steroid receptor coactivator-1 (SRC-1) specifically bound to the transcription
      factor AP-1 subunits c-Jun and c-Fos, as demonstrated by the yeast two-hybrid
      tests and glutathione S-transferase pull down assays. The c-Jun and c-Fos binding
      sites were localized to the C-terminal subregion of SRC-1 (amino acids 1101-1441)
      that encompasses the previously described histone acetyltransferase and receptor
      binding domains. In mammalian cells, SRC-1, similar to the previous results with
      CBP-p300 (Arias, J., Alberts, A. S., Brindle, P., Claret, F. X., Smeal, T.,
      Karin, M., Feramisco, J., and Montminy, M. (1994) Nature 370, 226-229; Bannister,
      A. J., and Kouzarides, T. (1995) EMBO J. 14, 4758-4762), potentiated the AP-1
      mediated transactivations in a dose-dependent manner and derepressed the mutual
      inhibitions between nuclear receptors and AP-1. Furthermore, coexpression of p300
      further enhanced this SRC-1-potentiated level of transactivations. Thus, we
      concluded that at least two distinct coactivator molecules may cooperate to
      regulate AP-1-dependent transactivations and mediate transrepression between AP-1
      and nuclear receptors in vivo.

PMID- 9642217
TI  - Transformation activity of Cdc42 requires a region unique to Rho-related
      proteins.
AB  - The Rho subfamily GTP-binding protein Cdc42 mediates actin cytoskeletal
      rearrangements and cell cycle progression and is essential for Ras
      transformation. Expression of a Cdc42 mutant (Cdc42(F28L)) that undergoes
      spontaneous activation (guanine nucleotide exchange) results in transformation of
      NIH3T3 fibroblasts. In this report, we show that deletion of residues 120-139
      from Cdc42(F28L), which comprise an insert region unique to Rho subfamily
      proteins but is missing in other GTP-binding proteins, yields a Cdc42 molecule
      that still undergoes spontaneous GTP-GDP exchange and stimulates both actin
      cytoskeletal changes and the activation of the cellular targets p21-activated
      kinase and the c-Jun kinase (JNK1). However, this Cdc42 mutant is unable to
      transform cells. These findings indicate that the Rho subfamily insert region is
      dispensable for many of the known signaling pathways initiated by activated Cdc42
      but is essential for its regulation of cell growth.

PMID- 9642218
TI  - Nerve growth factor is mitogenic for cancerous but not normal human breast
      epithelial cells.
AB  - We show here that nerve growth factor (NGF), the archetypal neurotrophic factor,
      is able to stimulate the proliferation of breast cancer cells (MCF-7 and MDA-MB
      231 cell lines), although it is unable to stimulate growth of normal breast
      epithelial cells (NBEC). This stimulation induced cells in the G0 phase to
      reenter the cell cycle, as well as shortening cell cycle duration. Immunoblotting
      experiments revealed that both the two cancer cell lines and the NBEC express
      high affinity (p140(trk)) and low affinity (p75) NGF receptors. Inhibition of the
      NGF growth-promoting effect by the drugs K-252a and PD98059 indicated that
      activation of Trk-tyrosine kinase activity and the mitogen-activated protein
      kinase cascade are necessary to obtain the mitogenic effect. Activation of
      mitogen-activated protein kinase can be detected in breast cancer cells after 10
      min of NGF stimulation, whereas no change was detected in NBEC. These results
      demonstrate that NGF is a mitogenic factor for human breast cancer cells and that
      it might constitute a new regulator of breast tumor growth.

PMID- 9642219
TI  - Regulation of the neutrophil respiratory burst oxidase. Identification of an
      activation domain in p67(phox).
AB  - Superoxide generation by the neutrophil respiratory burst oxidase (NADPH oxidase)
      can be reconstituted in a cell-free system using flavocytochrome b558 and the
      cytosolic proteins p47(phox), p67(phox), and Rac. p47(phox) functions as an
      adaptor protein; it increases the affinity of p67(phox) and Rac in the NADPH
      oxidase complex, but is not essential when high concentrations of these proteins
      are used (Freeman, J. L., and Lambeth, J. D. (1996) J. Biol. Chem. 271, 22578
      22582), implying that p67(phox) and/or Rac directly regulates enzyme activity.
      Herein, we describe an activation domain in p67(phox) that is essential for NADPH
      oxidase activity. A series of C-terminal truncation mutants of p67(phox) showed
      that residues 211 to the C terminus (residue 526) are not needed for cell-free
      activity. However, shorter truncations were inactive, pointing to an activation
      domain within the region spanning residues 199-210. p67(phox) mutated at single
      amino acid residues within this region showed diminished activity, and p67(phox)
      V204A was completely inactive. The effects of mutations on activity were
      independent of p47(phox), and mutations did not affect the binding of p67(phox)
      to Rac. In the presence of wild-type p67(phox), the V204A mutant was a potent
      inhibitor of superoxide generation, and inhibition was partially reversed by high
      concentrations of p67(phox), but not by p47(phox) or Rac. The V204A mutant
      competed with native p67(phox) for translocation to neutrophil plasma membrane,
      indicating that p67(phox) V204A assembles to form an inactive complex. The data
      imply a direct activation of flavocytochrome b558 by an activation domain in
      p67(phox).

PMID- 9642220
TI  - Odorants selectively activate distinct G protein subtypes in olfactory cilia.
AB  - Chemoelectrical signal transduction in olfactory neurons appears to involve
      intracellular reaction cascades mediated by heterotrimeric GTP-binding proteins.
      In this study attempts were made to identify the G protein subtype(s) in
      olfactory cilia that are activated by the primary (odorant) signal. Antibodies
      directed against the alpha subunits of distinct G protein subtypes interfered
      specifically with second messenger reponses elicited by defined subsets of
      odorants; odor-induced cAMP-formation was attenuated by Galphas antibodies,
      whereas Galphao antibodies blocked odor-induced inositol 1,4, 5-trisphosphate
      (IP3) formation. Activation-dependent photolabeling of Galpha subunits with
      [alpha-32P]GTP azidoanilide followed by immunoprecipitation using subtype
      specific antibodies enabled identification of particular individual G protein
      subtypes that were activated upon stimulation of isolated olfactory cilia by
      chemically distinct odorants. For example odorants that elicited a cAMP response
      resulted in labeling of a Galphas-like protein, whereas odorants that elicited an
      IP3 response led to the labeling of a Galphao-like protein. Since odorant-induced
      IP3 formation was also blocked by Gbeta antibodies, activation of olfactory
      phospholipase C might be mediated by betagamma subunits of a Go-like G protein.
      These results indicate that different subsets of odorants selectively trigger
      distinct reaction cascades and provide evidence for dual transduction pathways in
      olfactory signaling.

PMID- 9642221
TI  - A novel metal-activated pyridoxal enzyme with a unique primary structure, low
      specificity D-threonine aldolase from Arthrobacter sp. Strain DK-38. Molecular
      cloning and cofactor characterization.
AB  - The gene encoding low specificity D-threonine aldolase, catalyzing the
      interconversion of D-threonine/D-allo-threonine and glycine plus acetaldehyde,
      was cloned from the chromosomal DNA of Arthrobacter sp. strain DK-38. The gene
      contains an open reading frame consisting of 1,140 nucleotides corresponding to
      379 amino acid residues. The enzyme was overproduced in recombinant Escherichia
      coli cells and purified to homogeneity by ammonium sulfate fractionation and
      three-column chromatography steps. The recombinant aldolase was identified as a
      pyridoxal enzyme with the capacity of binding 1 mol of pyridoxal 5'-phosphate per
      mol of subunit, and Lys59 of the enzyme was determined to be the cofactor binding
      site by chemical modification with NaBH4. In addition, Mn2+ ion was demonstrated
      to be an activator of the enzyme, although the purified enzyme contained no
      detectable metal ions. Equilibrium dialysis and atomic absorption studies
      revealed that the recombinant enzyme could bind 1 mol of Mn2+ ion per mol of
      subunit. Remarkably, the predicted amino acid sequence of the enzyme showed no
      significant similarity to those of the currently known pyridoxal 5'-phosphate
      dependent enzymes, indicating that low specificity D-threonine aldolase is a new
      pyridoxal enzyme with a unique primary structure. Taken together, low specificity
      D-threonine aldolase from Arthrobacter sp. strain DK-38, with a unique primary
      structure, is a novel metal-activated pyridoxal enzyme.

PMID- 9642222
TI  - The Lutheran blood group glycoproteins, the erythroid receptors for laminin, are
      adhesion molecules.
AB  - The Lutheran antigens are recently characterized glycoproteins in which the
      extracellular region contains five immunoglobulin like domains, suggesting some
      recognition function. A recent abstract suggests that the Lutheran glycoproteins
      (Lu gps) act as erythrocyte receptors for soluble laminin (Udani, M., Jefferson,
      S., Daymont, C., Zen, Q., and Telen, M. J. (1996) Blood 88, Suppl. 1, 6
      (abstr.)). In the present report, we provided the definitive proof of the laminin
      receptor function of the Lu gps by demonstrating that stably transfected cells
      (murine L929 and human K562 cell lines) expressing the Lu gps bound laminin in
      solution and acquired adhesive properties to laminin-coated plastic dishes but
      not to fibronectin, vitronectin, transferrin, fibrinogen, or fibrin. Furthermore,
      expression of either the long-tail (85 kDa) or the short-tail (78 kDa) Lu gps,
      which differ by the presence or the absence of the last 40 amino acids of the
      cytoplasmic domain, respectively, conferred to transfected cells the same laminin
      binding capacity. We also confirmed by flow cytometry analysis that the level of
      laminin binding to red cells is correlated with the level of Lu antigen
      expression. Indeed, Lunull cells did not bind to laminin, whereas sickle cells
      from most patients homozygous for hemoglobin S overexpressed Lu antigens and
      exhibited an increased binding to laminin, as compared with normal red cells.
      Laminin binding to normal and sickle red cells as well as to Lu transfected cells
      was totally inhibited by a soluble Lu-Fc chimeric fragment containing the
      extracellular domain of the Lu gps. During in vitro erythropoiesis performed by
      two-phase liquid cultures of human peripheral blood, the appearance of Lu
      antigens in late erythroid differentiation was concomitant with the laminin
      binding capacity of the cultured erythroblasts. Altogether, our results
      demonstrated that long-tail and short-tail Lu gps are adhesion molecules that
      bind equally well laminin and strongly suggested that these glycoproteins are the
      unique receptors for laminin in normal and sickle mature red cells as well as in
      erythroid progenitors.

PMID- 9642223
TI  - Mitochondrial creatine kinase is a prime target of peroxynitrite-induced
      modification and inactivation.
AB  - The reaction of peroxynitrite (PN) with sarcomeric mitochondrial creatine kinase
      (Mib-CK; EC 2.7.3.2) was observed at different stages of complexity (i) with
      purified Mi-CK, (ii) with enzyme bound on isolated mitoplasts, and (iii) within
      intact respiring mitochondria. Creatine-stimulated respiration was abolished by
      PN concentrations likely to be physiological and far before the respiratory chain
      itself was affected, thus demonstrating that Mi-CK is a prime target for
      inactivation by PN in intact mitochondria. The inactivation by PN of Mi-CK was
      reversed by 22% with 2-mercaptoethanol. More remarkable protective effects were
      noticed with the full set of CK substrates, e.g. 30 and 50% protection with MgATP
      plus creatine and MgADP plus phosphocreatine, respectively, but not with each
      substrate alone. These data indicate an involvement of the active-site Cys-278
      residue of Mi-CK in this process. Furthermore, changes in endogenous tryptophan
      fluorescence intensity and spectral changes after reaction of Mi-CK with PN
      suggest additional modifications of Trp and Tyr residues. PN-inactivated Mi-CK
      can no longer be efficiently converted into dimers by incubation with reagents
      inducing a transition state analog complex at the active site. Thus, obviously,
      upon reaction of octameric Mi-CK with PN, the octamer-dimer equilibrium of Mi-CK
      is also affected. The consequences for cellular energy homeostasis and calcium
      handling are discussed.

PMID- 9642224
TI  - Differential regulation of discrete apoptotic pathways by Ras.
AB  - The products of the ras genes are known to regulate cell proliferation and
      differentiation; recently, they have been found to play a role in apoptosis. The
      expression of oncogenic p21(ras) in a number of cell types, including Jurkat (a
      human T lymphoblastoid cell line) and murine fibroblasts, makes the cells
      susceptible to apoptosis following suppression of protein kinase C (PKC) activity
      (PKC/Ras-mediated apoptosis). Engagement of Fas antigen, a potent effector of
      apoptosis, activates cellular p21(ras), which may be required for completion of
      the cell death program. To further investigate the role of p21(ras) in the
      regulation of apoptosis, the cellular mechanisms employed in these two apoptotic
      processes in which Ras activity is involved (PKC/Ras-related and Fas-triggered
      apoptosis), was explored. Increasing p21(ras) activity by expressing v-ras or by
      treatment with an antisense oligonucleotide to the GTPase-activating protein was
      found to accelerate the Fas-mediated apoptotic process in Jurkat and mouse LF
      cells. PKC/Ras-related apoptosis was associated with, and required, cell cycle
      progression, accompanied by the expression of the G1/S cyclins. In contrast, Fas
      engagement, although inducing a vigorous and PKC-independent activation of
      endogenous p21(ras), did not alter cell cycle progression, nor did it require
      such progression for apoptosis. Both the protein synthesis inhibitor
      cycloheximide and cyclin E antisense oligonucleotides partially abolished PKC/Ras
      mediated apoptosis but had only a moderate effect on Fas-induced apoptosis. In
      contrast, the CED-3/interleukin-1beta-converting enzyme (ICE) protease inhibitor
      Z-VADfmk efficiently suppressed Fas-induced apoptosis and only marginally
      inhibited PKC/Ras-mediated apoptosis. Induction of both pathways resulted in
      activation of the Jun NH2-terminal kinase/JUN signaling system. These results
      suggest that different cell death programs, such as PKC/Ras-mediated and Fas
      mediated apoptosis, may be interconnected via p21(ras) and perhaps Jun NH2
      terminal kinase/JUN. In response to various death stimuli, p21(ras) may act as a
      common intermediate regulator in the transduction of apoptotic signals.

PMID- 9642225
TI  - Expression of putative fatty acid transporter genes are regulated by peroxisome
      proliferator-activated receptor alpha and gamma activators in a tissue- and
      inducer-specific manner.
AB  - Regulation of gene expression of three putative long-chain fatty acid transport
      proteins, fatty acid translocase (FAT), mitochondrial aspartate aminotransferase
      (mAspAT), and fatty acid transport protein (FATP), by drugs that activate
      peroxisome proliferator-activated receptor (PPAR) alpha and gamma were studied
      using normal and obese mice and rat hepatoma cells. FAT mRNA was induced in liver
      and intestine of normal mice and in hepatoma cells to various extents only by
      PPARalpha-activating drugs. FATP mRNA was similarly induced in liver, but to a
      lesser extent in intestine. The induction time course in the liver was slower for
      FAT and FATP mRNA than that of an mRNA encoding a peroxisomal enzyme. An
      obligatory role of PPARalpha in hepatic FAT and FATP induction was demonstrated,
      since an increase in these mRNAs was not observed in PPARalpha-null mice. Levels
      of mAspAT mRNA were higher in liver and intestine of mice treated with peroxisome
      proliferators, while levels in hepatoma cells were similar regardless of
      treatment. In white adipose tissue of KKAy obese mice, thiazolidinedione
      PPARgamma activators (pioglitazone and troglitazone) induced FAT and FATP more
      efficiently than the PPARalpha activator, clofibrate. This effect was absent in
      brown adipose tissue. Under the same conditions, levels of mAspAT mRNA did not
      change significantly in these tissues. In conclusion, tissue-specific expression
      of FAT and FATP genes involves both PPARalpha and -gamma. Our data suggest that
      among the three putative long-chain fatty acid transporters, FAT and FATP appear
      to have physiological roles. Thus, peroxisome proliferators not only influence
      the metabolism of intracellular fatty acids but also cellular uptake, which is
      likely to be an important regulatory step in lipid homeostasis.

PMID- 9642226
TI  - Bcl-2 transcription from the proximal P2 promoter is activated in neuronal cells
      by the Brn-3a POU family transcription factor.
AB  - The BCL-2 protein is able to protect neuronal and other cell types from apoptotic
      programmed cell death and plays a key role in regulating the rate of apoptosis
      during development of the nervous system. We have previously demonstrated that
      the Brn-3a POU domain transcription factor protects sensory neurons from
      apoptotic programmed cell death induced by nerve growth factor withdrawal. We
      report here that Bcl-2 transcription is predominantly initiated from the Bcl-2 P2
      promoter in both the ND7 neuronal cell line and primary dorsal root ganglion
      neurons, in contrast to the predominant use of the Bcl-2 P1 promoter in other
      cell types. Moreover, Bcl-2 transcription initiated from the P2 region increases
      in ND7 cells stably overexpressing Brn-3a, resulting in enhanced BCL-2 protein
      levels. Similarly, the Bcl-2 P2 promoter is directly activated by Brn-3a in co
      transfection assays in both ND7 cells and dorsal root ganglion neurons. Analysis
      of the Bcl-2 regulatory sequence revealed a binding site for Brn-3a that is
      required for maximal activation by Brn-3a both in transfected cells and during
      differentiation of ND7 cells. Together these data identify Brn-3a as the first
      transcription factor regulating Bcl-2 activity specifically in neuronal cells and
      indicate that the anti-apoptotic effect of Brn-3a is likely to be mediated, at
      least in part, via the up-regulation of Bcl-2 expression.

PMID- 9642227
TI  - Osteoadherin, a cell-binding keratan sulfate proteoglycan in bone, belongs to the
      family of leucine-rich repeat proteins of the extracellular matrix.
AB  - Osteoadherin is a recently described bone proteoglycan containing keratan
      sulfate. It promotes integrin (alphav beta3)-mediated cell binding (Wendel, M.,
      Sommarin, Y., and Heinegard, D. (1998) J. Cell Biol. 141, 839-847). The primary
      structure of bovine osteoadherin has now been determined by nucleotide sequencing
      of a cDNA clone from a primary bovine osteoblast expression library. The entire
      translated primary sequence corresponds to a 49,116-Da protein with a calculated
      isoelectric point for the mature protein of 5.2. The dominating feature is a
      central region consisting of 11 B-type, leucine-rich repeats ranging in length
      from 20 to 30 residues. The full, primary sequence contains four putative sites
      for tyrosine sulfation, three of which are at the N-terminal end of the molecule.
      There are six potential sites for N-linked glycosylation present. Osteoadherin
      shows highest sequence identity, 42%, to bovine keratocan and 37-38% identity to
      bovine fibromodulin, lumican, and human PRELP. Unique to osteoadherin is the
      presence of a large and very acidic C-terminal domain. The distribution of
      cysteine residues resembles that of other leucine-rich repeat proteins except for
      two centrally located cysteines. Northern blot analysis of RNA samples from
      various bovine tissues showed a 4.5-kilobase pair message for osteoadherin to be
      expressed in bone only. Osteoadherin mRNA was detected by in situ hybridization
      in mature osteoblasts located superficially on trabecular bone.

PMID- 9642228
TI  - Production of adrenomedullin in macrophage cell line and peritoneal macrophage.
AB  - We demonstrate that adrenomedullin (AM) is produced and secreted from cultured
      murine monocyte/macrophage cell line (RAW 264.7) as well as mouse peritoneal
      macrophage. Immunoreactive (IR) AM secreted from RAW 264.7 cells was
      chromatographically identified to be native AM. To elucidate the regulation
      mechanism of AM production in macrophage, we examined the effects of various
      substances inducing differentiation or activation of monocyte/macrophage. Phorbol
      ester (TPA), retinoic acid (RA), lipopolysaccharide (LPS), and interferon-gamma
      (IFN-gamma) increased AM production 1.5-7-fold in RAW 264.7 cells in a dose- as
      well as time-dependent manner. By LPS stimulation, the AM mRNA level in RAW 264.7
      cells was augmented up to 7-fold after 14 h incubation. RA exerted a synergistic
      effect when administered with TPA, LPS, or IFN-gamma, whereas IFN-gamma
      completely suppressed AM production in RAW 264.7 cells stimulated with LPS.
      Dexamethasone, hydrocortisone, estradiol, and transforming growth factor-beta
      dose-dependently suppressed AM production in RAW 264.7 cells. AM production was
      also investigated in mouse peritoneal macrophage. Primary mouse macrophage
      secreted IR-AM at a rate similar to that of RAW 264.7 cells, and its production
      was enhanced 9-fold by LPS stimulation. AM was found to increase basal secretion
      of tumor necrosis factor alpha (TNF-alpha) from RAW 264.7 cells, whereas AM
      suppressed the secretion of TNF-alpha and interleukin-6 from that stimulated with
      LPS. Thus, macrophage should be recognized as one of the major sources of AM
      circulating in the blood. Especially in cases of sepsis and inflammation, AM
      production in macrophage is augmented, and the secreted AM is deduced to function
      as a modulator of cytokine production.

PMID- 9642229
TI  - Transforming potential of Dbl family proteins correlates with transcription from
      the cyclin D1 promoter but not with activation of Jun NH2-terminal kinase,
      p38/Mpk2, serum response factor, or c-Jun.
AB  - The dbl family of oncogenes encodes a large, structurally related, family of
      growth-regulatory molecules that possess guanine nucleotide exchange factor
      activity for specific members of the Rho family of Ras-related GTPases. We have
      evaluated matched sets of weakly and strongly transforming versions of five Dbl
      family proteins (Lfc, Lsc, Ect2, Dbl, and Dbs) to determine their ability to
      stimulate signaling pathways that are activated by Rho family proteins. We found
      that the transforming potential of this panel did not correlate directly with
      their ability to activate Jun NH2-terminal kinase, p38/Mpk2, serum response
      factor, or c-Jun. In contrast, transient stimulation of transcription from the
      cyclin D1 promoter provided a strong correlation with transforming potential, and
      we found constitutive up-regulation of cyclin D1 protein in Dbl family protein
      transformed cells. In addition, we observed that at least two Dbl family members
      (Lfc and Ect2) induced changes in the actin cytoskeleton and exhibited nuclear
      signaling profiles that are consistent with a broader range of in vivo substrate
      utilization than is predicted from their in vitro exchange specificities. In
      summary, although Dbl family proteins exhibit signaling profiles that are
      consistent with their in vivo activation of Rho proteins, stimulation of cyclin
      D1 transcription is the only activity that correlates with transforming
      potential, thus suggesting that deregulated cell cycle progression may be
      important for Dbl family protein transformation.

PMID- 9642230
TI  - Membrane fusion is induced by a distinct peptide sequence of the sea urchin
      fertilization protein bindin.
AB  - Fertilization in the sea urchin is mediated by the membrane-associated acrosomal
      protein bindin, which plays a key role in the adhesion and fusion between sperm
      and egg. We have investigated the structure/function relationship of an 18-amino
      acid peptide fragment "B18," which represents the minimal membrane binding motif
      of the protein and resembles a putative fusion peptide. The peptide was found to
      mimic the behavior of its parent protein bindin with respect to (a) its high
      affinity for lipid bilayers, (b) the ability to aggregate and fuse vesicles, (c)
      the binding of Zn2+ by a histidine-rich motif, (d) the tendency to self-assemble,
      and (e), as indicated earlier, the adhesion to cell surface polysaccharides.
      Fluorescence and light scattering assays were used here to monitor peptide
      induced lipid mixing, leakage, and aggregation of large unilamellar
      sphingomyelin/cholesterol vesicles. For these activities, B18 requires the
      presence of Zn2+ ions, with which it forms oligomeric complexes and assumes a
      partially alpha-helical conformation, as observed by circular dichroism. We
      conclude that aggregation and fusion involves a "trans-complex" between peptides
      on apposing vesicles that are connected by Zn2+ bridges.

PMID- 9642231
TI  - Common in vitro substrate specificity and differential Src homology 2 domain
      accessibility displayed by two members of the Src family of protein-tyrosine
      kinases, c-Src and Hck.
AB  - Hck and Src are members of the Src family of protein- tyrosine kinases that carry
      out distinct and overlapping functions in vivo (Lowell, C. A., Niwa, M., Soriano,
      P., and Varmus, H. E. (1996) Blood 87, 1780-1792). In an attempt to understand
      how Hck and Src can function both independently and in concert, we have compared
      1) their in vitro substrate specificity and 2) the accessibility of their Src
      homology 2 (SH2) domain. Using several synthetic peptides, we have demonstrated
      that Hck and Src recognize similar structural features in the substrate peptides,
      suggesting that both kinases have the intrinsic ability to carry out overlapping
      cellular functions by phosphorylating similar cellular proteins in vivo. Using a
      phosphotyrosine-containing peptide that has previously been shown to bind the SH2
      domain of Src family kinases with high affinity, we found that although Src could
      bind to the phosphopeptide, Hck showed no interaction. The inability of Hck to
      bind the phosphopeptide was not a result of a stable intramolecular interaction
      between its SH2 domain and C-terminal regulatory phosphotyrosine residue (Tyr
      520), as most Hck molecules in the purified Hck preparation were not tyrosine
      phosphorylated. In contrast to intact Hck, a recombinant truncation analog of Hck
      was able to bind the phosphopeptide with an affinity similar to that of the Src
      SH2 domain, suggesting that conformational constraints are imposed on intact Hck
      that limit accessibility of its SH2 domain to the phosphopeptide. Furthermore,
      the difference in SH2 domain accessibility is a potential mechanism that enables
      Src and Hck to perform their respective unique functions by 1) targeting them to
      different subcellular compartments, whereupon they phosphorylate different
      cellular proteins, and/or 2) facilitating direct binding to their cellular
      substrates.

PMID- 9642232
TI  - Altered properties of the branched chain amino acid-preferring activity
      contribute to increased cleavages after branched chain residues by the
      "immunoproteasome".
AB  - The multicatalytic proteinase complex (MPC, proteasome) is assembled from 14
      nonidentical protein subunits. It expresses five distinct proteolytic activities,
      including a chymotrypsin-like activity, cleaving after hydrophobic residues, and
      a branched chain amino acid-preferring component (BrAAP), cleaving preferentially
      after branched chain residues. Exposure of cells to interferons leads to
      replacement of the X, Y, and Z subunits by the LMP2, LMP7, and MECL1 subunits.
      This "immunoproteasome" is critical to processing of certain antigens. The
      enzymatic basis for enhanced antigen processing has not been determined. To gain
      insight into this question, we examined sites and relative rates of cleavage of
      bonds in denatured, reduced, carboxyamidomethylated lysozyme, a 129-amino acid
      protein, by MPC from bovine spleen, in which the X, Y, and Z subunits are
      replaced by LMP2, LMP7, and MECL1. We compared cleavages to those catalyzed by
      MPC from bovine pituitary, which contains only the X, Y, and Z subunits. We found
      marked increases in the rates and number of cleavages after branched chain
      residues in reduced, carboxyamidomethylated lysozyme by the spleen MPC. This was
      largely due to accelerated cleavages of bonds after a Phi-X-Br motif, where Phi
      is a hydrophobic residue, X is a small neutral or polar residue, and Br is a
      branched chain residue. Inhibitors with these structural properties were
      selective and potent inhibitors of the BrAAP activity of the spleen MPC. The
      above findings indicate that alterations in activity and substrate specificity of
      the BrAAP activity are important factors underlying the altered cleavages after
      hydrophobic residues associated with incorporation of interferon-inducible
      subunits. The potential relevance of the findings to antigen processing functions
      of MPC is discussed.

PMID- 9642233
TI  - Purification and characterization of a novel peptidase (IImes) from mesquite
      (Prosopis velutina) pollen.
AB  - Although the mesquite plant (Prosopis velutina) is not as widely distributed as
      some other allergenic species, its pollen can induce serious pollinosis in areas
      where it is localized. We previously isolated and characterized a peptidase from
      mesquite pollen with trypsin-like specificity (peptidase Imes) (Matheson, N.,
      Schmidt, J., and Travis, J. (1995) Am. J. Respir. Cell Mol. Biol. 12, 441-448).
      Now we have characterized a second enzyme with specificity for hydrophobic
      residues (mesquite pollen peptidase IImes). This enzyme has a molecular mass near
      92 kDa and activity that was not affected by reducing or chelating agents but was
      inhibited by specific synthetic serine proteinase inhibitors and the
      aminopeptidase inhibitor bestatin. However, it was not inhibited by human plasma
      proteinase inhibitors, nor did it inactivate any of those tested. The enzyme
      possessed amidolytic activity against p-nitroanilide substrates most effectively
      after alanine residues and also displayed aminopeptidase activity against non-p
      nitroanilide peptides with a preference for phenylalanine. This specificity for
      hydrophobic amino acid residues was corroborated by inhibition studies with
      chloromethyl ketone and organophosphonate inhibitors. More interesting from a
      physiological point of view is that the bioactive peptides, angiotensins I and II
      and vasoactive intestinal peptide, were also hydrolyzed rapidly, indicating an
      ability of peptidase IImes to act also as an oligopeptidase. Because these
      bioactive peptides play a role in the inflammatory responses in allergic asthma,
      our data suggest that the purified mesquite pollen peptidase IImes may be
      involved in the degradation of neuro- and vasoactive peptides during pollen
      initiated allergic reactions.

PMID- 9642234
TI  - Localization of the functional domains of human tissue inhibitor of
      metalloproteinases-3 and the effects of a Sorsby's fundus dystrophy mutation.
AB  - A transient COS-7 cell expression system was used to investigate the functional
      domain arrangement of tissue inhibitor of metalloproteinases-3 (TIMP-3),
      specifically to assess the contribution of the amino- and carboxyl-terminal
      domains of the molecule to its matrix metalloproteinase (MMP) inhibitory and
      extracellular matrix (ECM) binding properties. Wild type TIMP-3 was entirely
      localized to the ECM in both its glycosylated (27 kDa) and unglycosylated (24
      kDa) forms. A COOH-terminally truncated TIMP-3 molecule was found to be a non-ECM
      bound MMP inhibitor, whereas a chimeric TIMP molecule, consisting of the NH2
      terminal domain of TIMP-2 fused to the COOH-terminal domain of TIMP-3, displayed
      ECM binding, albeit with a lower affinity than the wild type TIMP-3 molecule.
      Thus the functional domain arrangement of TIMP-3 is analogous to that seen in
      TIMP-1 and -2, namely that the NH2-terminal domain is responsible for MMP
      inhibition whereas the COOH-terminal domain is most important in mediating the
      specific functions of the molecule. A mutant TIMP-3 in which serine 181 was
      changed to a cysteine, found in Sorsby's fundus dystrophy, a hereditary macular
      degenerative disease, was also expressed in COS-7 cells. This gave rise to an
      additional 48-kDa species (possibly a TIMP-3 dimer) that retained its ability to
      inhibit MMPs and localize to the ECM. These data favor the hypothesis that the
      TIMP-3 mutations seen in Sorsby's fundus dystrophy contribute to disease
      progression by accumulation of mutant protein rather than by the loss of
      functional TIMP-3.

PMID- 9642235
TI  - Guanine nucleotide exchange factors regulate specificity of downstream signaling
      from Rac and Cdc42.
AB  - The Rac and Cdc42 GTPases regulate diverse cellular behaviors involving the actin
      cytoskeleton, gene transcription, and the activity of multiple protein and lipid
      kinases. All of these pathways can potentially become activated when GTP-Rac or
      GTP-Cdc42 is formed in response to external cell signals, yet it is evident that
      each activity must also be able to be controlled individually. The mechanisms by
      which such specificity of GTPase signaling in response to upstream stimuli is
      achieved remains unclear. We investigated the action of several well
      characterized guanine nucleotide exchange factors (GEFRho) to activate Rac-
      and/or Cdc42-dependent kinase pathways. Coexpression studies in COS-7 cells
      revealed that the ability of individual guanine nucleotide exchange factors
      (GEFs) to activate the p21-activated kinase PAK1 could be dissociated from
      activation of c-Jun amino-terminal kinase, even though activation of both
      pathways requires the action of the GEFs on Rac and/or Cdc42. In contrast,
      expression of constitutively active forms of Rac or Cdc42 effectively stimulated
      both downstream kinases. We conclude that GEFs can be important determinants of
      downstream signaling specificity for members of the Rho GTPase family.

PMID- 9642236
TI  - Involvement of Ras in Bruton's tyrosine kinase-mediated JNK activation.
AB  - Defects in Bruton's tyrosine kinase (Btk) result in B cell immunodeficiencies in
      humans and mice. Recent studies showed that Btk is required for maximal
      activation of JNK, a family of stress-activated protein kinases, induced by
      several extracellular stimuli including interleukin (IL)-3. On the other hand, IL
      3-induced JNK activation is dependent on Ras. In the present study we have
      investigated whether Ras is involved in Btk-mediated JNK activation in BaF3 mouse
      pro-B cells. Overexpression of wild-type Btk protein in these cells enhanced JNK
      activation upon IL-3 stimulation, whereas expression of kinase-dead Btk partially
      suppressed JNK activation. Induced expression of the dominant negative Ras(N17)
      in the cells overexpressing wild-type Btk suppressed JNK activation. Importantly,
      overexpression of Btk enhanced the level of the GTP-bound, active form of Ras in
      response to IL-3 stimulation. Btk overexpression also increased the Shc-Grb2
      association induced by IL-3 stimulation. Expression of either N17Ras or V12Ras
      did not impose any effects on Btk kinase activity. These data collectively
      indicate that Ras plays a role of an intermediary signaling protein in Btk
      mediated JNK activation induced by the IL-3 signaling pathway.

PMID- 9642237
TI  - Protease IV, a unique extracellular protease and virulence factor from
      Pseudomonas aeruginosa.
AB  - Comparisons of virulence between a Pseudomonas parent strain and an isogenic
      mutant devoid of protease IV have demonstrated a significant role for this enzyme
      during infection. We have characterized purified Pseudomonas aeruginosa protease
      IV in terms of its biochemical and enzymatic properties, and found it to be a
      unique extracellular protease. The N-terminal decapeptide sequence of protease IV
      is not homologous with any published protein sequence. Protease IV has a
      molecular mass of 26 kDa, an isoelectric point of 8.70, and optimum enzymatic
      activity at pH 10.0 and 45 degreesC. Purified protease IV demonstrates activity
      for the carboxyl side of lysine-containing peptides and can digest a number of
      biologically important proteins, including immunoglobulin, complement components,
      fibrinogen, and plasminogen. Protease IV is not inhibited by thiol-, carboxyl-,
      or metalloproteinase inhibitors. The total loss of enzyme activity in the
      presence of N-p-tosyl-L-chloromethyl ketone and the partial inhibition of enzyme
      activity by diisopropyl fluorophosphate or phenylmethylsulfonyl fluoride imply
      that protease IV is a serine protease. Inhibition by dithiothreitol and beta
      mercaptoethanol suggests that intramolecular disulfide bonds are essential for
      enzyme activity. The characteristics of this enzyme suggest that inhibitors of
      serine proteases could be developed into a medication designed to arrest tissue
      damage during Pseudomonas infection.

PMID- 9642238
TI  - Identification and characterization of a conserved erythroid-specific enhancer
      located in intron 8 of the human 5-aminolevulinate synthase 2 gene.
AB  - Thirty five kilobases of sequence encompassing the human erythroid 5
      aminolevulinate synthase (ALAS2) gene have been determined. Analysis revealed a
      very low GC content, few repetitive elements, and evidence for the insertion of a
      reverse-transcribed mRNA sequence and a neighboring gene. We have investigated
      whether introns 1, 3, and 8, which correspond to DNase I-hypersensitivity sites
      in the structurally related mouse ALAS2 gene, affect expression of the human
      ALAS2 promoter in transient expression assays. Whereas intron 3 was marginally
      inhibitory, introns 1 and 8 of the human gene stimulated promoter activity.
      Intron 8 harbored a strong erythroid-specific enhancer activity which was
      orientation-dependent. Deletion analysis of this region localized enhancer
      activity to a fragment of 239 base pairs. Transcription factor binding sites
      clustered within this region include GATA motifs and CACCC boxes, critical
      regulatory sequences of many erythroid cell-expressed genes. These sites were
      also identified in the corresponding intron of both the murine and canine ALAS2
      genes. Mutagenesis of these conserved sites in the human intron 8 sequence and
      transient expression analysis in erythroid cells established the functional
      importance of one GATA motif and two CACCC boxes. The GATA motif bound GATA-1 in
      vitro. The two functional CACCC boxes each bound Sp1 or a related protein in
      vitro, but binding of the erythroid Kruppel-like factor and the basic Kruppel
      like factor could not be detected. The intron 8 enhancer region was not activated
      by GATA-1 together with Sp1 in transactivation experiments in COS-1 cells
      indicating the involvement of a related Sp1 protein or of another unidentified
      erythroid factor. Overall, these results demonstrate that a GATA-1-binding site
      and CACCC boxes located within the human ALAS2 intron 8 are critical for the
      erythroid-specific enhancer activity in transfected erythroid cells, and due to
      the conserved nature of these binding sites across species, it seems likely that
      these sites play a functional role in the tissue-restricted expression of the
      gene in vivo.

PMID- 9642239
TI  - Functional characterization of a cloned human kidney Na+:HCO3- cotransporter.
AB  - Functional properties of a cloned human kidney Na+:HCO3- cotransporter (NBC-1)
      were studied in cultured HEK-293 cells that were transiently transfected with NBC
      1 cDNA. The Na+:HCO3- cotransporter activity was assayed as the Na+ and HCO3
      dependent pHi recovery from intracellular acidosis with the use of the pH
      sensitive dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. In acid-loaded
      cells and in the presence of amiloride (to block Na+/H+ exchange), switching to a
      Na+-containing solution (115 mM) resulted in rapid pHi recovery only in the
      presence of HCO3-. This recovery was completely abolished by 300 microM 4, 4'
      diisothiocyanostilbene-2,2'-disulfonic acid. Replacing the Na+ with Li+ (115 mM)
      caused significant HCO3--dependent, DIDS-sensitive pHi recovery from
      intracellular acidosis, with Li+ showing lower affinity than Na+. Potassium (K+)
      had no affinity for the Na+:HCO3- cotransporter. The Na+-dependent HCO3-
      cotransport was abolished in the presence of 0.2 mM harmaline. The Na+:HCO3-
      cotransporter could also function in Na+:OH- cotransport mode, although only at
      high external pH (7.8). Based on functional similarities with the mammalian
      kidney experiments, we propose that NBC-1 is the proximal tubule Na+:HCO3-
      cotransporter.

PMID- 9642240
TI  - Cathepsin Z, a novel human cysteine proteinase with a short propeptide domain and
      a unique chromosomal location.
AB  - We have identified and characterized a novel human cysteine proteinase of the
      papain family. A full-length cDNA for this enzyme was cloned from a human brain
      cDNA library. Nucleotide sequence analysis revealed that the isolated cDNA codes
      for a polypeptide of 303 amino acids, tentatively called cathepsin Z, that
      exhibits structural features characteristic of cysteine proteinases. Fluorescent
      in situ hybridization experiments revealed that the human cathepsin Z gene maps
      to chromosome 20q13, a location that differs from all cysteine proteinase genes
      mapped to date. The cDNA encoding cathepsin Z was expressed in Escherichia coli
      as a fusion protein with glutathione S-transferase, and after purification, the
      recombinant protein was able to degrade the synthetic peptide benzyloxycarbonyl
      Phe-Arg-7-amido-4-methylcoumarin, used as a substrate for cysteine proteinases.
      Northern blot analysis demonstrated that cathepsin Z is widely expressed in human
      tissues, suggesting that this enzyme could be involved in the normal
      intracellular protein degradation taking place in all cell types. Cathepsin Z is
      also ubiquitously distributed in cancer cell lines and in primary tumors from
      different sources, suggesting that this enzyme may participate in tumor
      progression as reported for other cathepsins. Finally, on the basis of a series
      of distinctive structural features, including diverse peptide insertions and an
      unusual short propeptide, together with its unique chromosomal location among
      cysteine proteinases, we propose that cathepsin Z may be the first representative
      of a novel subfamily of this class of proteolytic enzymes.

PMID- 9642241
TI  - Calcium enhances heparin catalysis of the antithrombin-factor Xa reaction by a
      template mechanism. Evidence that calcium alleviates Gla domain antagonism of
      heparin binding to factor Xa.
AB  - It is believed that heparin accelerates factor Xa (FXa) inactivation by
      antithrombin (AT) by conformationally activating the inhibitor rather than by
      bridging AT and FXa in a ternary complex (template effect). This is derived from
      kinetic studies done in the absence of Ca2+ or in the presence of EDTA. To test
      the possibility that the anionic Gla domain of FXa, when not neutralized by Ca2+
      ions, prevents heparin binding to FXa, the heparin and pentasaccharide dependence
      of FXa inactivation by AT in both the absence (100 microM EDTA) and presence of
      Ca2+ (2.5 mM) was studied using wild-type FXa and a FXa derivative that lacks the
      Gla domain (GDFXa). AT inactivated both FXa derivatives similarly in both the
      absence and presence of Ca2+ (k2 = 1.7-2.5 x 10(3) M-1 s-1). The active AT
      binding pentasaccharide also accelerated the inactivation rates of both
      derivatives similarly in both the absence and presence of Ca2+ (k2 = 5.7-8.0 x
      10(5) M-1 s-1). However, in the presence of an optimum concentration of heparin (
      approximately 50 nM) the inactivation rate constant of FXa in the presence of
      Ca2+ (k2 = 4.4 x 10(7) M-1 s-1) was 13-fold higher than the rate constant in the
      absence of Ca2+ (k2 = 3.5 x 10(6) M-1 s-1). Heparin acceleration of GDFXa
      inactivation by AT was rapid and insensitive to the presence or absence of Ca2+
      (k2 = 5.1-5.9 x 10(7) M-1 s-1). The additional cofactor effect of heparin with
      all FXa derivatives was a bell-shaped curve, which disappeared if the ionic
      strength of the reaction was increased to approximately 0.4. These results
      suggest that although the major effect of heparin in acceleration of FXa
      inactivation is through a heparin-induced conformational change in the reactive
      site loop of AT, the template effect of heparin, nevertheless, contributes
      significantly to rapid FXa inactivation at physiological Ca2+.

PMID- 9642242
TI  - C5 convertase of the alternative pathway of complement. Kinetic analysis of the
      free and surface-bound forms of the enzyme.
AB  - Although proteolytic activation of the complement protein C5 initiates important
      defensive and occasionally pathological inflammatory reactions, the enzymatic
      properties of the enzymes responsible for this cleavage have never been examined.
      We have studied the kinetic parameters of the C5 convertase of the alternative
      pathway of complement, either bound to a zymosan surface or in its monomeric
      soluble form. C5 convertase enzymatic activity was measured as a function of C5
      concentration by quantitating production of C5b,6 under physiological conditions
      of temperature, pH, and ionic strength. The C5 convertases appeared to follow
      Michaelis-Menten kinetics and exhibited similar catalytic rate constants (kcat).
      However, the surface-bound enzyme, ZymC3b,Bb had a Km (1.4 microM) that was 17
      times lower than that of the soluble monomeric form of the enzyme, C3b,Bb (Km =
      24 microM). The kcat for the cell-bound enzyme, ZymC3b,Bb was 0.0048 s-1 and that
      for soluble C3b,Bb was 0.0110 s-1. Both forms of the enzyme had a low turnover
      number at Vmax (0.23 to 0.68 C5/min/enzyme). Substituting Mg2+ for Ni2+ did not
      alter the kinetic parameters but lowered the half-life of the enzyme by 5-7-fold.
      The kinetic data presented demonstrate that the fluid phase C5 convertase,
      C3b,Bb, can cleave C5 without the aid of a second C3b molecule. The results also
      show that the greater enzymatic activity previously observed for the surface
      bound C5 convertases is not due to higher catalytic efficiency but is solely due
      to higher affinity for the substrate C5. In blood, C5 concentrations are 3-4-fold
      below the Km determined for the surface-bound C5 convertase suggesting a direct
      correlation between the local C5 concentration and production of the
      anaphylatoxin C5a and the cytolytic C5b-9 complex.

PMID- 9642243
TI  - Differential expression and biological effects of insulin-like growth factor
      binding protein-4 and -5 in vascular smooth muscle cells.
AB  - Insulin-like growth factor-I (IGF-I) plays an important role in regulating
      vascular smooth muscle cell (VSMC) proliferation, migration, and apoptosis. The
      bioactivity of IGF-I is modulated by a group of high affinity, specific binding
      proteins (IGF-binding proteins; IGFBPs) that are present in the interstitial
      fluid. Previously, we have reported that porcine VSMCs synthesize and secrete IGF
      I and several forms of IGFBPs, including IGFBP-2, IGFBP-4, and IGFBP-5. In this
      study, we examined the role of autocrine/paracrine secreted IGF-I in controlling
      the expression of IGFBP-4 and IGFBP-5 as well as the effects of these IGFBPs in
      modulating the cellular replication response to IGF-I. The concentrations of
      IGFBP-4 in the conditioned medium increased significantly from <50 ng/ml to 742
      +/- 105 ng/ml. This increase was associated with a decrease in the activity of an
      IGF-I-regulated IGFBP-4 protease. In contrast, the synthesis of IGFBP-5 was
      inversely correlated with culture density, and its concentration decreased from
      792 +/- 91 to 44 +/- 14 ng/ml. IGFBP-5 mRNA in sparse cultures was 3-fold higher
      compared with those in confluent cultures. This culture density-dependent change
      in IGFBP-5 mRNA correlated closely with endogenous IGF-I levels. Since treatment
      of VSMC with exogenous IGF-I increased IGFBP-5 mRNA levels, we neutralized the
      effect of endogenously secreted IGF-I with an anti-IGF-I antibody to determine if
      it would alter IGFBP-5 mRNA abundance. This resulted in a 4.4-fold decrease in
      IGFBP-5 mRNA levels. When added together with IGF-I, exogenous IGFBP-4 inhibited
      IGF-I-induced DNA synthesis in a concentration-dependent manner. IGFBP-5, on the
      other hand, potentiated the effect of IGF-I. Therefore, IGFBP-4 and IGFBP-5
      appear to be differentially regulated by autocrine/paracrine IGF-I through
      distinct mechanisms. These two proteins, in turn, play opposing roles in
      modulating IGF-I action in stimulating VSMC proliferation.

PMID- 9642244
TI  - Recognition of a human arrest site is conserved between RNA polymerase II and
      prokaryotic RNA polymerases.
AB  - DNA sequences that arrest transcription by either eukaryotic RNA polymerase II or
      Escherichia coli RNA polymerase have been identified previously. Elongation
      factors SII and GreB are RNA polymerase-binding proteins that enable readthrough
      of arrest sites by these enzymes, respectively. This functional similarity has
      led to general models of elongation applicable to both eukaryotic and prokaryotic
      enzymes. Here we have transcribed with phage and bacterial RNA polymerases, a
      human DNA sequence previously defined as an arrest site for RNA polymerase II.
      The phage and bacterial enzymes both respond efficiently to the arrest signal in
      vitro at limiting levels of nucleoside triphosphates. The E. coli polymerase
      remains in a template-engaged complex for many hours, can be isolated, and is
      potentially active. The enzyme displays a relatively slow first-order loss of
      elongation competence as it dwells at the arrest site. Bacterial RNA polymerase
      arrested at the human site is reactivated by GreB in the same way that RNA
      polymerase II arrested at this site is stimulated by SII. Very efficient
      readthrough can be achieved by phage, bacterial, and eukaryotic RNA polymerases
      in the absence of elongation factors if 5-Br-UTP is substituted for UTP. These
      findings provide additional and direct evidence for functional similarity between
      prokaryotic and eukaryotic transcription elongation and readthrough mechanisms.

PMID- 9642245
TI  - Limitations of the mass isotopomer distribution analysis of glucose to study
      gluconeogenesis. Heterogeneity of glucose labeling in incubated hepatocytes.
AB  - We previously reported (Previs, S. F., Fernandez, C. A., Yang, D., Soloviev, M.
      V., David, F., and Brunengraber, H. (1995) J. Biol. Chem. 270, 19806-19815) that
      glucose made in isolated livers from starved rats perfused with physiological
      concentrations of lactate, pyruvate, and either [2-13C]- or [U-13C3]glycerol had
      a mass isotopomer distribution incompatible with glucose being made from a
      homogeneously labeled pool of triose phosphates. Similar data were obtained in
      live rats infused with [U-13C3]glycerol. We ascribed the labeling heterogeneity
      to major decreases in glycerol concentration and enrichment across the liver. We
      concluded that [13C]glycerol is unsuitable for tracing the contribution of
      gluconeogenesis to total glucose production. We now report isotopic heterogeneity
      of gluconeogenesis in hepatocytes, even when all cells are in contact with
      identical concentrations and enrichments of gluconeogenic substrates. Total rat
      hepatocytes were incubated with concentrations of glycerol, lactate, and pyruvate
      that were kept constant by substrate infusions. To modulate competition between
      substrates, the (glycerol)/(lactate + pyruvate) infusion ratio ranged from 0.23
      to 3. 60. Metabolic and isotopic steady states were achieved in all cases. The
      apparent contribution of gluconeogenesis to glucose production (f) was calculated
      from the mass isotopomer distribution of glucose. When all substrates were 13C
      labeled, f was 97%, as expected in glycogen-deprived hepatocytes. As the infusion
      ratio ([13C]glycerol)/(lactate + pyruvate) increased, f increased from 73% to
      94%. In contrast, as the infusion ratio (glycerol)/([13C]lactate + [13C]pyruvate)
      increased, f decreased from 93% to 76%. In all cases, f increased with the rate
      of supply of the substrate that was labeled. Variations in f show that the 13C
      labeling of triose phosphates was not equal in all hepatocytes, even when exposed
      to the same substrate concentrations and enrichments. We also showed that
      zonation of glycerol kinase activity is minor in rat liver. We conclude that
      zonation of other processes than glycerol phosphorylation contributes to the
      heterogeneity of triose phosphate labeling from glycerol in rat liver.

PMID- 9642246
TI  - Conversion of temperature-sensitive to -resistant gene expression due to
      mutations in the promoter region of the melibiose operon in Escherichia coli.
AB  - The melibiose utilization system of Escherichia coli W3133, a derivative of K12,
      is nonfunctional between 37 and 42 degreesC. The reason for this temperature
      sensitivity was thought to be that the melibiose transporter (MelB) of W3133
      cells was temperature-sensitive. A mutant W3133-2 has been isolated as a
      temperature-resistant strain that can utilize melibiose between 37 and 42
      degreesC. However, we found that the melibiose transporter of the W3133-2 was
      still temperature-sensitive. Half-life activities of the melibiose transporter at
      37 degreesC (or 40 degreesC) in both E. coli W3133 and W3133-2 were exactly the
      same. Furthermore, we found that the nucleotide sequence of coding region of the
      melB structural gene (the second gene of the melibiose operon) of W3133-2 was
      exactly the same as that of W3133. Activity of alpha-galactosidase (product of
      the first gene, melA, of the melibiose operon) of W3133 cells grown at 40
      degreesC was very low, although that of W3133-2 cells grown at 40 degreesC was
      high. These observations suggested that expression of the melibiose operon in
      W3133 is also temperature-sensitive. In fact, we found that the expression in
      W3133 cells was temperature-sensitive, while that in W3133-2 cells was
      temperature-resistant, by analyzing mRNA levels using the Northern blot method.
      Furthermore, we identified mutations in the promoter region of the melibiose
      operon of W3133-2 that resulted in the elongation of an 18 nucleotide inverted
      repeat sequence to a 28-nucleotide repeat sequence present immediately upstream
      of the -35 region. This may stabilize a possible stem structure due to the
      inverted repeat at 37-42 degreesC.

PMID- 9642247
TI  - Cannabinoid receptor agonist efficacy for stimulating [35S]GTPgammaS binding to
      rat cerebellar membranes correlates with agonist-induced decreases in GDP
      affinity.
AB  - The relationship between GDP and cannabinoid-stimulated [35S]guanosine-5'-O-(3
      thiotriphosphate) ([35S]GTPgammaS) binding was investigated in rat cerebellar
      membranes. Kinetic analyses showed that [35S]GTPgammaS binding reached steady
      state levels and that the association rate was increased by the agonist WIN 55212
      2 proportional to the concentration of GDP. Dissociation of [35S]GTPgammaS
      occurred with two rates (t1/2 = 7 and 170 min), and WIN 55212-2 increased the
      proportion of sites exhibiting the faster rate. Without GDP, [35S]GTPgammaS bound
      to membranes with high and low affinity, and WIN 55212-2 had no effect. With 30
      microM GDP, [35S]GTPgammaS bound to low and intermediate affinity sites, and WIN
      55212-2 induced high affinity [35S]GTPgammaS binding without affecting low
      affinity sites. GDP competed for high affinity [35S]GTPgammaS binding with high
      and intermediate affinity in the absence of WIN 55212-2 and with high and low
      affinity in the presence of WIN 55212-2. Cannabinoid ligands displayed
      differential abilities to maximally stimulate [35S]GTPgammaS binding in the
      presence of GDP. Efficacy differences among ligands increased with increasing GDP
      concentrations. GDP competition curves revealed that agonists induced low
      affinity GDP Ki values that were proportional to agonist Emax values, indicating
      that agonist efficacy is determined by displacement of GDP from G-proteins.

PMID- 9642248
TI  - Inhibition of activating transcription factor 1- and cAMP-responsive element
      binding protein-activated transcription by an intracellular single chain Fv
      fragment.
AB  - Activating transcription factor 1 (ATF1) and cAMP-responsive element (CRE)
      binding protein (CREB) activate transcription through CREs located in the
      promoters of cellular and viral genes. We previously described a monoclonal
      antibody (mAb41.4) that prevents ATF1 binding to DNA and reduces CRE-driven
      promoter activity in vitro (Orten, D. J., Strawhecker, J. M., Sanderson, S. D.,
      Huang, D., Prytowsky, M. B. , and Hinrichs, S. H. (1994) J. Biol. Chem. 269,
      32254-32263). A single chain Fv (scFv) fragment from the mAb41.4-expressing
      hybridoma was generated to provide a means to investigate transcription factor
      function via intracellular expression of the scFv fragment. The affinity of scFv4
      (subgroup: VL kappa-III, VH miscellaneous) for ATF1 was similar to that of the
      parental mAb and the Fab fragment, but it demonstrated greater inhibitory
      activity and reacted with CREB. scFv4 disrupted the binding of both ATF1 and CREB
      in electrophoretic mobility shift assays and reduced expression of CRE-driven
      expression in vitro. Transient expression of scFv had no effect on the non-CRE
      containing adenovirus major late promoter. The proliferating cell nuclear antigen
      promoter, containing two CREs, was significantly more sensitive to inhibition by
      scFv than the cytomegalovirus immediate-early promoter, containing five CREs.
      Cotransfection of either ATF1 or CREB in the presence of scFv restored basal
      levels of expression. The intracellular expression of scFv provides a unique
      means to investigate the roles of the transcription factors ATF1 and CREB.

PMID- 9642249
TI  - NF-Y organizes the gamma-globin CCAAT boxes region.
AB  - The CCAAT-binding activator NF-Y is formed by three evolutionary conserved
      subunits, two of which contain putative histone-like domains. We investigated NF
      Y binding to all CCAAT boxes of globin promoters in direct binding, competition,
      and supershift electrophoretic mobility shift assay; we found that the alpha,
      zeta, and proximal gamma CCAAT boxes of human and the prosimian Galago bind
      avidly, and distal gamma CCAAT boxes have intermediate affinity, whereas the
      epsilon and beta sequences bind NF-Y very poorly. We developed an efficient in
      vitro transcription system from erythroid K562 cells and established that both
      the distal and the proximal CCAAT boxes are important for optimal gamma-globin
      promoter activity. Surprisingly, NF-Y binding to a mutated distal CCAAT box (a C
      to T at position -114) is remarkably increased upon occupancy of the high
      affinity proximal element, located 27 base pairs away. Shortening the distance
      between the two CCAAT boxes progressively prevents simultaneous CCAAT binding,
      indicating that NF-Y interacts in a mutually exclusive way with CCAAT boxes
      closer than 24 base pairs apart. A combination of circular permutation and
      phasing analysis proved that (i) NF-Y-induced angles of the two gamma-globin
      CCAAT boxes have similar amplitudes; (ii) occupancy of the two CCAAT boxes leads
      to compensatory distortions; (iii) the two NF-Y bends are spatially oriented with
      combined twisting angles of about 100 degrees. Interestingly, such distortions
      are reminiscent of core histone-DNA interactions. We conclude that NF-Y binding
      imposes a high level of functionally important coordinate organization to the
      gamma-globin promoter.

PMID- 9642250
TI  - Evidence for a ligand interaction site at the amino-terminus of the parathyroid
      hormone (PTH)/PTH-related protein receptor from cross-linking and mutational
      studies.
AB  - Low resolution mutational studies have indicated that the amino-terminal
      extracellular domain of the rat parathyroid hormone (PTH)/PTH-related protein
      (PTHrP) receptor (rP1R) interacts with the carboxyl-terminal portion of PTH-(1
      34) or PTHrP-(1-36). To further define ligand-receptor interactions, we prepared
      a fully functional photoreactive analog of PTHrP, [Ile5,Bpa23,Tyr36]PTHrP-(1-36)
      amide ([Bpa23]PTHrP, where Bpa is p-benzoyl-L-phenylalanine). Upon photolysis,
      radioiodinated [Bpa23]PTHrP covalently and specifically bound to the rP1R. CNBr
      cleavage of the broad approximately 80-kDa complex yielded a radiolabeled
      approximately 9-kDa non-glycosylated protein band that could potentially be
      assigned to rP1R residues 23-63, Tyr23 being the presumed amino-terminus of the
      receptor. This assignment was confirmed using a mutant rP1R (rP1R-M63I) that
      yielded, upon photoligand binding and CNBr digestion, a broad protein band of
      approximately 46 kDa, which was reduced to a sharp band of approximately 20 kDa
      upon deglycosylation. CNBr digestion of complexes formed with two additional rP1R
      double mutants (rP1R-M63I/L40M and rP1R-M63I/L41M) yielded non-glycosylated
      protein bands that were approximately 6 kDa in size, indicating that [Bpa23]PTHrP
      cross-links to amino acids 23-40 of the rP1R. This segment overlaps a receptor
      region previously identified by deletion mapping to be important for ligand
      binding. Alanine scanning of this region revealed two residues, Thr33 and Gln37,
      as being functionally involved in ligand binding. Thus, the convergence of
      photoaffinity cross-linking and mutational data demonstrates that the extreme
      amino-terminus of the rP1R participates in ligand binding.

PMID- 9642251
TI  - Patch clamp studies on ion pumps of the cytoplasmic membrane of Escherichia coli.
      Formation, preparation, and utilization of giant vacuole-like structures
      consisting of everted cytoplasmic membrane.
AB  - Formation of giant protoplasts from normal Escherichia coli cells resulted in the
      formation of giant vacuole-type structures (which we designate as provacuoles) in
      the protoplasts. Electron microscopic observation revealed that these provacuoles
      were surrounded by a single membrane. We detected inner (cytoplasmic) membrane
      proteins in the provacuolar membrane but not outer membrane proteins. Biochemical
      analyses revealed that the provacuoles consist of everted cytoplasmic membranes.
      We applied the patch clamp method to the giant provacuoles. We have succeeded in
      measuring current that represents inward movement of H+ because of respiration
      and to ATP hydrolysis by the FoF1-ATPase. Such current was inhibited by
      inhibitors of the respiratory chain or FoF1-ATPase. This method is applicable for
      analyses of ion channels, ion pumps, or ion transporters in E. coli or other
      microorganisms.

PMID- 9642252
TI  - Applied pressure enhances cell proliferation through mitogen-activated protein
      kinase activation in mesangial cells.
AB  - Progressive renal diseases lead to prolonged glomerular hypertension, which
      induces the proliferation of mesangial cells. This proliferation is thought to be
      involved in the development of renal injury. Here we investigate mitogen
      activated protein kinase (MAPK) activation and cell proliferation in mesangial
      cells under conditions of high pressure. After pressure-load, the phosphorylation
      level of MAPK (at Tyr-204) increases rapidly with a peak at 1 min, although the
      amount of MAPK remains almost constant during pressure-load. To confirm the
      activation of MAPK, we carried out an immunoprecipitation-kinase assay. MAPK
      activity during pressure-load shows kinetics similar to that of the tyrosine
      phosphorylation. In contrast, c-Jun N-terminal kinase 1 (JNK1) phosphorylation
      falls below basal levels in response to high pressure. Immunocytochemical
      observations show phosphorylated MAPK in the nucleus at 10 min. The expression of
      c-Fos, a nuclear transcription factor, is induced by high pressure, and the
      induction is significantly inhibited by PD98059 (50 microM), an upstream
      MAPK/extracellular signal-regulated kinase kinase (MEK) inhibitor of MAPK. The
      expression of the c-Jun that is induced by JNK1 activation remains unchanged
      during pressure-load. MAPK phosphorylation and cell proliferation by applied
      pressure are significantly inhibited by genistein, a tyrosine kinase inhibitor in
      a dose-dependent manner, but not by protein kinase C inhibitors, chelerythrine
      and GF109203X. Genistein also blocks pressure-induced tyrosine phosphorylation of
      proteins with molecular masses of 35, 53, and 180 kDa. To clarify the
      physiological role in MAPK activation under high pressure conditions, we
      transfected antisense MAPK DNA into mesangial cells. The antisense DNA (2 microM)
      inhibited MAPK expression by 80% compared with expression in the presence of
      sense or scrambled DNA, and significantly blocked pressure-induced cell
      proliferation. Treatment of cells with MEK inhibitor also produced a similar
      result. MEK inhibitor strongly suppresses DNA synthesis induced by pressure-load.
      Cyclin D1 expression is significantly increased under high pressure conditions,
      and the increase is blocked by treatment with MEK inhibitor. These findings show
      that pressure-load, a novel activator of MAPK, induces the activation of tyrosine
      kinases, and enhances the proliferation of mesangial cells, probably through
      cyclin D1 expression.

PMID- 9642253
TI  - Identification of a potential effector pathway for the trimeric Go protein
      associated with secretory granules. Go stimulates a granule-bound
      phosphatidylinositol 4-kinase by activating RhoA in chromaffin cells.
AB  - Besides having a role in signal transduction, heterotrimeric G proteins may be
      involved in membrane trafficking events. In chromaffin cells, Go is associated
      with secretory organelles, and its activation inhibits the ATP-dependent priming
      of exocytosis. By using permeabilized cells, we previously described that the
      control exerted by the granule-bound Go on exocytosis may be related to effects
      on the cortical actin network through a sequence possibly involving Rho. To
      provide further insight into the function of Rho in exocytosis, we focus here on
      its intracellular localization in chromaffin cells. By immunoreplica analysis,
      immunoprecipitation, and confocal immunofluorescence, we found that RhoA is
      specifically associated with the membrane of secretory chromaffin granules.
      Parallel subcellular fractionation experiments revealed the occurrence of a
      mastoparan-stimulated phosphatidylinositol 4-kinase activity in purified
      chromaffin granule membranes. This stimulatory effect of mastoparan was mimicked
      by GAP-43, an activator of the granule-associated Go, and specifically inhibited
      by antibodies against Galphao. In addition, Clostridium botulinum C3 exoenzyme
      completely blocked the activation of phosphatidylinositol 4-kinase by mastoparan.
      We propose that the control exerted by Go on peripheral actin and exocytosis is
      related to the activation of a downstream RhoA-dependent phosphatidylinositol 4
      kinase associated with the membrane of secretory granules.

PMID- 9642254
TI  - Induction of the erythropoietin receptor gene and acquisition of responsiveness
      to erythropoietin by stem cell factor in HML/SE, a human leukemic cell line.
AB  - HML/SE is a cytokine-dependent cell line established from childhood acute
      megakaryoblastic leukemia. Granulocyte-macrophage colony-stimulating factor or
      stem cell factor (SCF) alone could stimulate proliferation of HML/SE cells,
      however interleukin-3, interleukin-6, granulocyte colony-stimulating factor and
      thrombopoietin could not. Although erythropoietin (EPO) alone stimulated neither
      proliferation nor differentiation of HML/SE cells, it did stimulate proliferation
      of HML/SE cells and production of hemoglobin in the presence of SCF. SCF
      activated the human EPO receptor promoter and induced EPO receptor gene
      expression. Given these results, we speculate that HML/SE cells acquired
      responsiveness to EPO via the EPO receptor induced by SCF. Mutation analysis of
      putative transcription factor binding sites in the human EPO receptor promoter
      suggested that Sp1, rather than the GATA-1 binding site, contributed to the
      induction of the hEPOR gene. Although it is well documented that hematopoietic
      stem cells and primitive progenitors require both an early-acting cytokine and a
      lineage-specific cytokine to differentiate to a certain lineage, related
      mechanisms are not well understood. HML/SE may serve as an excellent model system
      to analyze functions of early-acting cytokine SCF and lineage-specific cytokine
      EPO related to proliferation and differentiation of hematopoietic stem cells.

PMID- 9642255
TI  - Characterization of a variant iron protein of nitrogenase that is impaired in its
      ability to adopt the MgATP-induced conformational change.
AB  - An Azotobacter vinelandii nitrogenase iron protein mutant has been created which
      contains an alanine to glycine substitution at amino acid 157. The strain
      expressing this mutant Fe protein is able to grow under nitrogen-fixing
      conditions. This contrasts with an A. vinelandii strain described previously
      which is unable to grow under nitrogen-fixing conditions and which expresses an
      Fe protein variant that has an alanine to serine mutation at position 157. The
      A157S Fe protein was unable to support substrate reduction by nitrogenase because
      of an inability to undergo a required MgATP-induced conformational change.
      Although the A157G strain grows at 55% of the rate of the wild-type strain,
      purified A157G Fe protein is only able to support substrate reduction in in vitro
      assays at a rate that is approximately 20% of the rate supported by the wild-type
      Fe protein. Electron paramagnetic resonance, circular dichroism spectroscopies,
      and enzymatic activity data indicate that the A157G Fe protein adopts the correct
      conformation upon the binding of MgATP. However, kinetic studies using chelation
      show that this protein undergoes the conformational change more slowly than the
      wild-type protein. Thus, this mutant has lower activity because of an impaired
      ability to undergo this conformational change. Comparison of two available x-ray
      crystal structures of the native Fe protein alone and complexed with the MoFe
      protein has provided us with a model to explain the change in activity in alanine
      157 mutants. Steric interactions with the side chain of residue 157 influence the
      protein's ability to undergo the initial MgATP-induced conformational change. In
      the case of the A157G mutant, however, once the correct conformation is attained,
      the protein can participate in all subsequent reactions including complex
      formation, electron transfer, and MgATP hydrolysis. Thus, the role of alanine 157
      is to stabilize the proper initial conformation upon MgATP binding.

PMID- 9642256
TI  - PRMT 3, a type I protein arginine N-methyltransferase that differs from PRMT1 in
      its oligomerization, subcellular localization, substrate specificity, and
      regulation.
AB  - Methylation is one of the many post-translational modifications that modulate
      protein function. Although asymmetric NG,NG-dimethylation of arginine residues in
      glycine-arginine-rich domains of eucaryotic proteins, catalyzed by type I protein
      arginine N-methyltransferases (PRMT), has been known for some time, members of
      this enzyme class have only recently been cloned. The first example of this type
      of enzyme, designated PRMT1, cloned because of its ability to interact with the
      mammalian TIS21 immediate-early protein, was then shown to have protein arginine
      methyltransferase activity. We have now isolated rat and human cDNA orthologues
      that encode proteins with substantial sequence similarity to PRMT1. A recombinant
      glutathione S-transferase (GST) fusion product of this new rat protein, named
      PRMT3, asymmetrically dimethylates arginine residues present both in the designed
      substrate GST-GAR and in substrate proteins present in hypomethylated extracts of
      a yeast rmt1 mutant that lacks type I arginine methyltransferase activity; PRMT3
      is thus a functional type I protein arginine N-methyltransferase. However, rat
      PRMT1 and PRMT3 glutathione S-transferase fusion proteins have distinct enzyme
      specificities for substrates present in both hypomethylated rmt1 yeast extract
      and hypomethylated RAT1 embryo cell extract. TIS21 protein modulates the
      enzymatic activity of recombinant GST-PRMT1 fusion protein but not the activity
      of GST-PRMT3. Western blot analysis of gel filtration fractions suggests that
      PRMT3 is present as a monomer in RAT1 cell extracts. In contrast, PRMT1 is
      present in an oligomeric complex. Immunofluorescence analysis localized PRMT1
      predominantly to the nucleus of RAT1 cells. In contrast, PRMT3 is predominantly
      cytoplasmic.

PMID- 9642257
TI  - Gbeta binding to GIRK4 subunit is critical for G protein-gated K+ channel
      activation.
AB  - The cardiac G protein-gated K+ channel, IKACh, is directly activated by G protein
      beta gamma subunits (Gbeta gamma). IKAChis composed of two inward rectifier K+
      channel subunits, GIRK1 and GIRK4. Gbeta gamma binds to both GIRK1 and GIRK4
      subunits of the heteromultimeric IKACh. Here we delineate the Gbeta gamma binding
      regions of IKACh by studying direct Gbeta gamma interaction with native purified
      IKACh, competition of this interaction with peptides derived from GIRK1 or GIRK4
      amino acid sequences, mutational analysis of regions implicated in Gbeta gamma
      binding, and functional expression of mutated subunits in mammalian cells. Only
      two GIRK4 peptides, containing amino acids 209-225 or 226-245, effectively
      competed for Gbeta gamma binding. A single point mutation introduced into GIRK4
      at position 216 (C216T) dramatically reduced the potency of the peptide in
      inhibiting Gbeta gamma binding and Gbeta gamma activation of expressed
      GIRK1/GIRK4(C216T) channels. Conversion of 5 amino acids in GIRK4 (226-245) to
      the corresponding amino acids found in the G protein-insensitive IRK1 channel,
      completely abolished peptide inhibition of Gbeta gamma binding to IKACh and Gbeta
      gamma activation of GIRK1/mutant GIRK4 channels. We conclude from this data that
      Gbeta gamma binding to GIRK4 is critical for IKACh activation.

PMID- 9642258
TI  - E-cadherin regulates anchorage-independent growth and survival in oral squamous
      cell carcinoma cells.
AB  - Integrin-basement membrane interactions provide essential signals that promote
      survival and growth of epithelial cells, whereas loss of such adhesions triggers
      programmed cell death. We found that HSC-3 human squamous carcinoma cells
      survived and grew readily as monolayers, but when they were suspended as single
      cells, they ceased proliferating and entered into the apoptotic death pathway,
      characterized by DNA fragmentation. In contrast, if the suspended carcinoma cells
      were permitted to form E-cadherin-mediated multicellular aggregates, they not
      only survived but proliferated. However, aggregated normal keratinocytes were
      unable to survive in suspension culture and rapidly became apoptotic. Anchorage
      independence and resistance to apoptosis of HSC-3 cell aggregates required high
      levels of extracellular Ca2+ and was inhibited with function-perturbing anti-E
      cadherin antibody. Resistance to suspension-induced apoptosis in cell aggregates
      paralleled the up-regulation of Bcl-2 but occurred in the absence of focal
      adhesion kinase activation. Analysis of suspension-induced death in a set of
      cloned squamous epithelial cell lines with different levels of E-cadherin
      expression revealed that receptor-positive cell clones evaded apoptosis and
      proliferated in three-dimensional aggregate culture, whereas cadherin-negative
      clones failed to survive. Collectively, these observations indicate that cadherin
      mediated intercellular adhesions generate a compensatory mechanism that promotes
      anchorage-independent growth and suppresses apoptosis.

PMID- 9642259
TI  - Structure of tetrameric human phenylalanine hydroxylase and its implications for
      phenylketonuria.
AB  - Phenylalanine hydroxylase (PheOH) catalyzes the conversion of L-phenylalanine to
      L-tyrosine, the rate-limiting step in the oxidative degradation of phenylalanine.
      Mutations in the human PheOH gene cause phenylketonuria, a common autosomal
      recessive metabolic disorder that in untreated patients often results in varying
      degrees of mental retardation. We have determined the crystal structure of human
      PheOH (residues 118-452). The enzyme crystallizes as a tetramer with each monomer
      consisting of a catalytic and a tetramerization domain. The tetramerization
      domain is characterized by the presence of a domain swapping arm that interacts
      with the other monomers forming an antiparallel coiled-coil. The structure is the
      first report of a tetrameric PheOH and displays an overall architecture similar
      to that of the functionally related tyrosine hydroxylase. In contrast to the
      tyrosine hydroxylase tetramer structure, a very pronounced asymmetry is observed
      in the phenylalanine hydroxylase, caused by the occurrence of two alternate
      conformations in the hinge region that leads to the coiled-coil helix.
      Examination of the mutations causing PKU shows that some of the most frequent
      mutations are located at the interface of the catalytic and tetramerization
      domains. Their effects on the structural and cellular stability of the enzyme are
      discussed.

PMID- 9642260
TI  - RIP2 is a novel NF-kappaB-activating and cell death-inducing kinase.
AB  - Through specific interactions with members of the tumor necrosis receptor (TNFR)
      family, adapter molecules such as the serine/threonine (Ser/Thr) kinase RIP
      mediate divergent signaling pathways including NF-kappaB activation and cell
      death. In this study, we have identified and characterized a novel 61-kDa protein
      kinase related to RIP that is a component of both the TNFR-1 and the CD40
      signaling complexes. Receptor interacting protein-2 (RIP2) contains an N-terminal
      domain with homology to Ser/Thr kinases and a C-terminal caspase activation and
      recruitment domain (CARD), a homophilic interaction motif that mediates the
      recruitment of caspase death proteases. Overexpression of RIP2 signaled both NF
      kappaB activation and cell death. Mutational analysis revealed the pro-apoptotic
      function of RIP2 to be restricted to its C-terminal CARD domain, whereas the
      intact molecule was necessary for NF-kappaB activation. RIP2 interacted with
      other members of the TNFR-1 signaling complex, including inhibitor of apoptosis
      protein cIAP1 and with members of the TNFR-associated factor (TRAF) family,
      specifically TRAF1, TRAF5, and TRAF6, but not with TRAF2, TRAF3, or TRAF4. These
      TRAF interactions mediate the recruitment of RIP2 to receptor signaling
      complexes.

PMID- 9642261
TI  - Human ecalectin, a variant of human galectin-9, is a novel eosinophil
      chemoattractant produced by T lymphocytes.
AB  - A 1.6-kilobase pair cDNA was isolated from a human T-cell-derived expression
      library that encodes a novel eosinophil chemoattractant (designated ecalectin)
      expressed during allergic and parasitic responses. Based on its deduced amino
      acid sequence, ecalectin is a 36-kDa protein consisting of 323 amino acids.
      Although ecalectin lacks a hydrophobic signal peptide, it is secreted from
      mammalian cells. Ecalectin is not related to any known cytokine or chemokine but
      rather is a variant of human galectin-9, a member of the large family of animal
      lectins that have affinity for beta-galactosides. Recombinant ecalectin,
      expressed in COS cells and insect cells, exhibited potent eosinophil
      chemoattractant activity and attracted eosinophils in vitro and in vivo in a dose
      dependent manner but not neutrophils, lymphocytes, or monocytes. The finding that
      the ecalectin transcript is present in abundance in various lymphatic tissues and
      that its expression increases substantially in antigen-activated peripheral blood
      mononuclear cells suggests that ecalectin is an important T-cell-derived
      regulator of eosinophil recruitment in tissues during inflammatory reactions. We
      believe that this is the first report of the expression of an immunoregulatory
      galectin expressed by a T-cell line that is selective for eosinophils.

PMID- 9642262
TI  - Interaction of BAG-1 with retinoic acid receptor and its inhibition of retinoic
      acid-induced apoptosis in cancer cells.
AB  - BAG-1 (also known as RAP46) is an anti-apoptotic protein, which has been shown
      previously to interact with a number of nuclear hormone receptors, including
      receptors for glucocorticoid, estrogen, and thyroid hormone. We show here that
      BAG-1 also interacts with retinoic acid receptor (RAR). Gel retardation assays
      demonstrated that in vitro translated BAG-1 protein could effectively inhibit the
      binding of RAR but not retinoid X receptor (RXR) to a number of retinoic acid
      (RA) response elements (RAREs). A glutathione S-transferase-BAG-1 fusion protein
      also specifically bound RAR but not RXR. Interaction of BAG-1 and RAR could also
      be demonstrated by yeast two-hybrid assays. In transient transfection assays, co
      transfection of BAG-1 expression plasmid inhibited the transactivation activity
      of RAR/RXR heterodimers but not RXR/RXR homodimers. When stably expressed in
      breast cancer cell lines, BAG-1 inhibited binding of RAR/RXR heterodimer to a
      number of RAREs and suppressed RA-induced growth inhibition and apoptosis. In
      addition, RA-induced suppression of Bcl-2 expression was abrogated by
      overexpression of BAG-1. These results demonstrate that BAG-1 can regulate
      retinoid activities through its interaction with RAR and suggest that elevated
      levels of BAG-1 protein could potentially contribute to retinoid resistance in
      cancer cells.

PMID- 9642263
TI  - Human ADAM 12 (meltrin alpha) is an active metalloprotease.
AB  - The ADAMs (a disintegrin and metalloprotease) are a family of multidomain
      proteins with structural homology to snake venom metalloproteases. We recently
      described the cloning and sequencing of human ADAM 12 (meltrin alpha). In this
      report we provide evidence that the metalloprotease domain of ADAM 12 is
      catalytically active. We used the trapping mechanism of alpha2-macroglobulin to
      assay for protease activity of wild-type and mutant ADAM 12 proteins produced in
      a COS cell transfection system. We found that ADAM 12 is synthesized as a
      zymogen, with the prodomain maintaining the metalloprotease in a latent form,
      probably by means of a cysteine switch. The zymogen could be activated chemically
      by alkylation with N-ethylmaleimide. Cleavage of the prodomain at a site for a
      furin-like endopeptidase resulted in an ADAM 12 protein with proteolytic
      activity. The protease activity was sensitive to inhibition by 1,10
      phenanthroline and could be eliminated by mutation of the critical glutamate
      residue at the active site. The demonstration that the ADAM 12 metalloprotease
      domain is functional may have important implications for future studies that
      explore the role of ADAM 12 protein in development and disease.

PMID- 9642264
TI  - The mini-hemoglobins in neural and body wall tissue of the nemertean worm,
      Cerebratulus lacteus.
AB  - Hemoglobin (Hb) occurs in circulating red blood cells, neural tissue, and body
      wall muscle tissue of the nemertean worm, Cerebratulus lacteus. The neural and
      body wall tissue each express single major Hb components for which the amino acid
      sequences have been deduced from cDNA and genomic DNA. These 109-residue globins
      form the smallest stable Hbs known. The globin genes have three exons and two
      introns with splice sites in the highly conserved positions of most globin genes.
      Alignment of the sequences with those of other globins indicates that the A, B,
      and H helices are about one-half the typical length. Phylogenetic analysis
      indicates that shortening results in a small tendency of globins to group
      together regardless of their actual relationships. The neural and body wall Hbs
      in situ are half-saturated with O2 at 2.9 and 4.1 torr, respectively. The Hill
      coefficient for the neural Hb in situ, approximately 2.9, suggests that the
      neural Hb self-associates in the deoxy state at least to tetramers at the 2-3 mM
      (heme) concentration estimated in the cells. The Hb must dissociate upon
      oxygenation and dilution because the weight-average molecular mass of the HbO2 in
      vitro is only about 18 kDa at 2-3 microM heme concentration. Calculations suggest
      that the Hb can function as an O2 store capable of extending neuronal activity in
      an anoxic environment for 5-30 min.

PMID- 9642265
TI  - Tyrosine and tryptophan act through the same binding site at the dimer interface
      of yeast chorismate mutase.
AB  - Tyrosine and tryptophan are the regulators of the dimeric yeast chorismate
      mutase. Biochemical studies reveal two binding sites per molecule for both
      effectors, tyrosine or tryptophan. A single binding site is built up by helix 8
      and helices 4 and 5 of two different subunits. The binding sites have been
      analyzed in the active enzyme by site directed mutagenesis of critical codons of
      the coding gene, ARO7. Gly-141 and Ser-142, which both reside on helix 8, are
      involved in the binding of tyrosine or tryptophan presumably by interacting
      specifically with the amino- and carboxylate-groups of these amino acid
      effectors. Interaction with Thr-145 of helix 8 is required for a strong tyrosine
      binding to the allosteric site. Replacement of Arg-75, which connects helices 4
      and 5 or of Arg-76, which is part of helix 5 by alanine residues, resulted in
      unregulated enzymes. These two residues are bonded to the carboxylate group and
      phenolic hydroxyl group of tyrosine, respectively, but do not interact with
      tryptophan by hydrogen bonding in the crystal structures. Phenylalanine, which
      has low binding affinity slightly activated the chorismate mutase. A T145V mutant
      chorismate mutase, however, showed increased activation by phenylalanine. Our
      results support a mechanism by which tyrosine contracts the allosteric site by
      interacting with its phenolic hydroxyl group. Tryptophan works in an inverse way
      by opening the allosteric site through the steric size of its side chain.

PMID- 9642266
TI  - Mutations at nonliganding residues Tyr-85 and Glu-83 in the N-lobe of human serum
      transferrin. Functional second shell effects.
AB  - The x-ray crystal structure of the N-lobe of human serum transferrin has shown
      that there is a hydrogen bond network, the so-called "second shell," around the
      transferrin iron binding site. Tyrosine at position 85 and glutamic acid at
      position 83 are two nonliganding residues in this network in the human serum
      transferrin N-lobe (hTF/2N). Mutation of each of these two amino acids has a
      profound effect on the metal binding properties of hTF/2N. When Tyr-85 is mutated
      to phenylalanine, iron release from the resulting mutant Y85F is much more facile
      than from the parent protein. Elimination of the hydrogen bond between Tyr-85 and
      Lys-296 appears to interfere with the "di-lysine (Lys-206-Lys-296) trigger,"
      which affects the iron binding stability of the protein. Surprisingly, mutation
      of Glu-83 to alanine leads to the absence of one of the normal iron binding
      ligands; introduction of a monovalent anion is able to restore the normal first
      coordination sphere. The missing ligand appears to be His-249, as revealed by
      comparison of the metal binding behaviors of mutants H249Q and E83A and
      structural analysis. Glu-83 has a strong H bond linkage with His-249 in apo
      hTF/2N, which helps to hold the His-249 in the proper position for iron binding.
      Disabling Glu-83 by mutation to an alanine seriously disturbs the H bond network,
      allowing His-249 to move away. A monovalent anion can help reestablish the normal
      network by providing a negative charge near the position of Glu-83 to reach
      charge balance, so that ligand His-249 is available again for iron binding.

PMID- 9642267
TI  - A B-cell-specific DNA recombination complex.
AB  - We have purified and biochemically characterized a multiprotein complex
      designated SWAP. In a DNA transfer assay, SWAP preferentially recombines
      ("swaps") sequences derived from Ig heavy chain switch regions. We identified
      four of the proteins in the SWAP complex: B23 (nucleophosmin), C23 (nucleolin),
      poly(ADP-ribose) polymerase (PARP), and SWAP-70. The first three are proteins
      known to be present in most cells. B23 promotes single-strand DNA reannealing and
      the formation of joint molecules in a D-loop assay between homologous, but also
      between Smu and Sgamma sequences. SWAP-70 is a novel protein of 70 kDa. Its cDNA
      was cloned and sequenced, and the protein was overexpressed in Escherichia coli.
      SWAP-70 protein expression was found only in B lymphocytes that had been induced
      to switch to various Ig isotypes and in switching B-cell lines. SWAP-70 is a
      nuclear protein, has a weak affinity for DNA, binds ATP, and forms specific, high
      affinity complexes with B23, C23, and poly(ADP-ribose) polymerase. These findings
      are consistent with SWAP being the long elusive "switch recombinase" and with
      SWAP-70 being the specific recruiting element that assembles the switch
      recombinase from universal components.

PMID- 9642268
TI  - Identification of the binding site on cytochrome P450 2B4 for cytochrome b5 and
      cytochrome P450 reductase.
AB  - A model of cytochrome P450 2B4, which was constructed by homology modeling with
      the four known crystal structures of the cytochromes P450 (Chang, T.-T.,
      Stiffelman, O. B., Vakser, I. A., Loew, G. H., Bridges, A., and Waskell, L.
      (1997) Protein Eng. 10, 119-129), was used to select amino acids predicted, by
      computer docking studies and numerous previous biochemical and site-directed
      mutagenesis studies, to be involved in binding the heme domain of cytochrome b5.
      Twenty-four amino acid residues located on both the distal and the proximal
      surface of the molecule were chosen for mutagenesis. These 24 mutant proteins
      were expressed in Escherichia coli, purified, and characterized with respect to
      their ability to bind cytochrome b5 and support substrate oxidation. Seven
      mutants, R122A, R126A, R133A, F135A, M137A, K139A, and K433A, all on the proximal
      surface of cytochrome P450 2B4 near the heme ligand, were identified that
      exhibited decreased ability to bind cytochrome b5. All of the mutants except
      K433A are located in either the C or C* helices or their termini. In addition,
      these seven mutants and two additional mutants on the proximal surface of
      cytochrome P450, R422A and R443A, were shown to exhibit decreased binding to
      cytochrome P450 reductase. These studies indicate that the binding sites for
      cytochrome b5 and cytochrome P450 reductase are, as predicted, located on the
      proximal surface of cytochrome P450 2B4 and are partially overlapping but not
      identical.

PMID- 9642269
TI  - Full activation of the platelet-derived growth factor beta-receptor kinase
      involves multiple events.
AB  - Activation of receptor tyrosine kinases is thought to involve ligand-induced
      dimerization, which promotes receptor transphosphorylation and thereby increases
      the receptor's phosphotransferase activity. We used two platelet-derived growth
      factor beta-receptor (beta-PDGFR) mutants to identify events that are required
      for full engagement (autophosphorylation and activation of the kinase activity)
      of the beta-PDGFR kinase. The F79/81 receptor (Tyr to Phe substitution at 579 and
      581 in the juxtamembrane domain of the receptor) was capable of only very modest
      ligand-dependent autophosphorylation and also failed to associate with numerous
      SH2 domain-containing proteins. Furthermore, stimulation with platelet-derived
      growth factor (PDGF) did not increase the kinase activity of the F79/81 mutant
      toward exogenous substrates. However, the F79/81 receptor had basal kinase
      activity and could be artificially stimulated by incubation with ATP. Because the
      low kinase activity of the F857 mutant (Tyr to Phe substitution at 857 in the
      putative activation loop) could not be increased by incubation with ATP, failure
      to phosphorylate Tyr-857 may be the reason why the F79/81 mutant has low kinase
      activity. Surprisingly, the F857 mutant underwent efficient PDGF-dependent
      autophosphorylation. Thus the PDGF-dependent increase in the kinase activity of
      the receptor is not required for autophosphorylation. We conclude that full
      activation of the beta-PDGFR kinase requires at least two, apparently distinct
      events.

PMID- 9642270
TI  - Distinct saturable pathways for the endocytosis of different tyrosine motifs.
AB  - Endocytosis of surface proteins through clathrin-coated pits requires an
      internalization signal in the cytoplasmic domain. Two types of internalization
      signal have been described: one requiring a tyrosine as the critical residue
      (tyrosine-based motif), and the other consisting of either two consecutive
      leucines or an isoleucine and leucine (dileucine motif). Although it seems that
      these signals are necessary and sufficient for endocytic targeting, the mechanism
      of recognition is not well understood. To examine this question, tetracycline
      repressible cell lines were used to overexpress one of several receptors bearing
      a tyrosine-based internalization signal. By measuring the rates of endocytosis
      for either the overexpressed receptor, or that of other endogenous receptors, we
      were able to show that the endocytosis of identical receptors could be saturated,
      but a complete lack of competition exists between the transferrin receptor (TfR),
      the low-density lipoprotein receptor, and the epidermal growth factor receptor.
      Overexpression of any one of these receptors resulted in its redistribution
      toward the cell surface, implying that entry into coated pits is limited. During
      high levels of TfR expression, however, a significant increase in the amount of
      surface Lamp1, but not low-density lipoprotein receptor, epidermal growth factor
      receptor, or Lamp2, is detected. This suggests that Lamp1 and TfR compete for the
      same endocytic sites. Together, these results support the idea that there are at
      least three distinct saturable components involved in clathrin-mediated
      endocytosis.

PMID- 9642271
TI  - Inhibition of glucose trimming with castanospermine reduces calnexin association
      and promotes proteasome degradation of the alpha-subunit of the nicotinic
      acetylcholine receptor.
AB  - To identify factors involved in the expression of ligand-gated ion channels, we
      expressed nicotinic acetylcholine receptors in HEK cells to characterize roles
      for oligosaccharide trimming, calnexin association, and targeting to the
      proteasome. The homologous subunits of the acetylcholine receptor traverse the
      membrane four times, contain at least one oligosaccharide, and are retained in
      the endoplasmic reticulum until completely assembled into the circular
      arrangement of subunits of delta-alpha-gamma-alpha-beta to enclose the ion
      channel. We previously demonstrated that calnexin is associated with unassembled
      subunits of the receptor, but appears to dissociate when subunits are assembled
      in various combinations. We used the glucosidase inhibitor castanospermine to
      block oligosaccharide processing, and thereby inhibit calnexin's interaction with
      the oligosaccharides in the receptor subunits. Castanospermine treatment reduces
      the association of calnexin with the alpha-subunit of the receptor, and
      diminishes the intracellular accumulation of unassembled receptor subunit
      protein. However, treatment with castanospermine does not appear to alter subunit
      folding or assembly. In contrast, co-treatment with proteasome inhibitors and
      castanospermine enhances the accumulation of polyubiquitin-conjugated alpha
      subunits, and generally reverses the castanospermine induced loss of alpha
      subunit protein. Co-transfection of cDNAs encoding the alpha- and delta-subunits,
      which leads to the expression of assembled alpha- and delta- subunits, also
      inhibits the loss of alpha-subunits expressed in the presence of castanospermine.
      Taken together, these observations indicate that calnexin association reduces the
      degradation of unassembled receptor subunits in the ubiquitin-proteasome pathway.

PMID- 9642272
TI  - Functional defects of a muscle-specific calpain, p94, caused by mutations
      associated with limb-girdle muscular dystrophy type 2A.
AB  - p94 (calpain3), a muscle-specific member of the calpain family, has been shown to
      be responsible for limb-girdle muscular dystrophy type 2A (LGMD2A), a form of
      autosomal recessive and progressive neuromuscular disorder. To elucidate the
      molecular mechanism of LGMD2A, we constructed nine p94 missense point mutants
      found in LGMD2A and analyzed their p94 unique properties. All mutants completely
      or almost completely lose the proteolytic activity against a potential substrate,
      fodrin. However, some of the mutants still possess autolytic activity and/or
      connectin/titin binding ability, indicating these properties are not necessary
      for the LGMD2A phenotypes. These results provide strong evidence that LGMD2A
      results from the loss of proteolysis of substrates by p94, suggesting a novel
      molecular mechanism leading to muscular dystrophies.

PMID- 9642273
TI  - Identification of a novel bone morphogenetic protein-responsive gene that may
      function as a noncoding RNA.
AB  - Bone morphogenetic proteins (BMPs)/osteogenic proteins (OPs), members of the
      transforming growth factor-beta superfamily, have a wide variety of effects on
      many cell types including osteoblasts and chondroblasts, and play critical roles
      in embryonic development. BMPs transduce their effects through binding to two
      different types of serine/threonine kinase receptors, type I and type II.
      Signaling by these receptors is mediated by the recently identified Smad
      proteins. Despite the rapid progress in understanding of the signaling mechanism
      downstream of BMP receptors, the target genes of BMPs are poorly understood in
      mammals. Here we identified a novel gene, termed BMP/OP-responsive gene (BORG),
      in C2C12 mouse myoblast cell line which trans-differentiates into osteoblastic
      cells in response to BMPs. Expression of BORG was dramatically induced in C2C12
      cells by the treatment with BMP-2 or OP-1 within 2 h and peaked at 12-24 h,
      whereas transforming growth factor-beta had a minimal effect. BMP-dependent
      expression of BORG was also detected in other cell types which are known to
      respond to BMPs, suggesting that BORG is a common target gene of BMPs. Cloning
      and sequence analysis of BORG cDNA and the genomic clones revealed that,
      unexpectedly, the transcript of BORG lacks any extensive open reading frames and
      contains a cluster of multiple interspersed repetitive sequences in its middle
      part. The unusual structural features suggested that BORG may function as a
      noncoding RNA, although it is spliced and polyadenylated as authentic protein
      coding mRNAs. Together with the observation that transfection of antisense
      oligonucleotides of BORG partially inhibited BMP-induced differentiation in C2C12
      cells, it is possible that a new class of RNA molecules may have certain roles in
      the differentiation process induced by BMPs.

PMID- 9642274
TI  - Five discrete cis-active domains direct cell type-specific transcription of the
      vasoactive intestinal peptide (VIP) gene.
AB  - Vasoactive intestinal peptide (VIP) is a neuromodulator expressed with great
      anatomical specificity throughout the nervous system. Cell-specific expression of
      the VIP gene is mediated by a tissue specifier element (TSE) located within a 2.7
      kilobase (kb) region between -5.2 and -2.5 kb upstream from the transcription
      start site, and requires an intact promoter proximal VIP-CRE (cyclic AMP
      responsive element) (Hahm, S. H., and Eiden, L. E. (1997) J. Neurochem. 67, 1872
      1881). We now report that the TSE comprises a 425-base pair domain located
      between -4.7 and -4.2 kb containing two AT-rich octamer-like sequences. The 425
      base pair TSE is sufficient to provide full cell-specific regulation of the VIP
      gene, when fused to the 5' proximal 1.55 kb of the VIP gene. Mutational analysis
      and gel shift assays of these octamer-like sequences indicate that the binding of
      proteins related to the ubiquitously expressed POU-homeodomain proteins Oct-1
      and/or Oct-2 to these octamer-like sequences plays a central role for the
      function of the TSE. The TSE interacts with three additional discrete domains
      besides the cAMP response element, which are located within the proximal 1.55 kb
      of the VIP gene, to provide cell-specific expression. An upstream domain from 
      1.55 to -1.37 kb contains E-boxes and MEF2-like motifs, and deletion of this
      domain results in complete abrogation of cell-specific transcriptional activity.
      The region from -1.37 to -1. 28 kb contains a STAT motif, and further removal of
      this domain allows the upstream TSE to act as an enhancer in both SH-EP and HeLa
      cells. The sequence from -1.28 to -0.9 kb containing a non-canonical AP-1 binding
      sequence (Symes, A., Gearan, T., Eby, J., and Fink, J. S. (1997) J. Biol. Chem.
      272, 9648-9654), is absolutely required for TSE-dependent cellspecific expression
      of the VIP gene. Thus, five discrete domains of the VIP gene provide a
      combination of enhancer and repressor activities, each completely contingent on
      VIP gene context, that together result in cell-specific transcription of the VIP
      gene.

PMID- 9642275
TI  - Cell cycle- and chromatin binding state-dependent phosphorylation of human MCM
      heterohexameric complexes. A role for cdc2 kinase.
AB  - The mammalian MCM protein family, presently with six members, exists in the
      nuclei in two forms, chromatin-bound and unbound. The former dissociates from
      chromatin with progression through the S phase. Recently, we have established a
      procedure to isolate chromatin-bound and unbound complexes containing all six
      human MCM (hMCM) proteins by immunoprecipitation. In the present study, we
      applied this procedure to HeLa cells synchronized in each of the G1, S, and G2/M
      phases and could detect hMCM heterohexameric complexes in all three. In addition,
      depending on the cell cycle and the state of chromatin association, hMCM2 and 4
      in the complexes were found to variously change their phosphorylation states.
      Concentrating attention on G2/M phase hyperphosphorylation, we found hMCM2 and 4
      in the complexes to be good substrates for cdc2/cyclin B in vitro. Furthermore,
      when cdc2 kinase was inactivated in temperature-sensitive mutant murine FT210
      cells, the G2/M hyperphosphorylation of the murine MCM2 and MCM4 and release of
      the MCMs from chromatin in the G2 phase were severely impaired. Taken together,
      the data suggest that the six mammalian MCM proteins function and undergo cell
      cycle-dependent regulation as heterohexameric complexes and that phosphorylation
      of the complexes by cdc2 kinase may be one of mechanisms negatively regulating
      the MCM complex-chromatin association.

PMID- 9642276
TI  - Caspases cleave focal adhesion kinase during apoptosis to generate a FRNK-like
      polypeptide.
AB  - Focal adhesion kinase (Fak) is a non-receptor protein-tyrosine kinase that
      stimulates cell spreading and motility by promoting the formation of contact
      sites between the cell and the extracellular matrix (focal adhesions). It
      suppresses apoptosis by transducing survival signals that emanate from focal
      adhesions via the clustering of transmembrane integrins by components of the
      extracellular matrix. We demonstrate that Fak is cleaved by caspases at two
      distinct sites during apoptosis. The sites were mapped to DQTD772, which was
      preferentially cleaved by caspase-3, and VSWD704, which was preferentially
      cleaved by caspase-6 and cytotoxic T lymphocyte-derived granzyme B. The cleavage
      of Fak during apoptosis separates the tyrosine kinase domain from the focal
      adhesion targeting (FAT) domain. The carboxyl-terminal fragments that are
      generated suppress phosphorylation of endogenous Fak and thus resemble a natural
      variant of Fak, FRNK, that inhibits Fak activity by preventing the localization
      of Fak to focal adhesions. The cleavage of Fak by caspases may thus play an
      important role in the execution of the suicide program by disabling the anti
      apoptotic function of Fak. Interestingly, rodent Fak lacks an optimal caspase-3
      consensus cleavage site although it is cleaved in murine cells undergoing
      apoptosis at an upstream site. This appears to be the first example of a caspase
      substrate where the cleavage sites are not conserved between species.

PMID- 9642277
TI  - The amino-terminal domain of human STAT4. Overproduction, purification, and
      biophysical characterization.
AB  - The multifunctional signal transducer and activator of transcription (STAT)
      proteins relay signals from the cell membrane to the nucleus in response to
      cytokines and growth factors. STAT4 becomes activated when cells are treated with
      interleukin-12, a key cytokine regulator of cell-mediated immunity. Upon
      activation, dimers of STAT4 bind cooperatively to tandem interferon-gamma
      activation sequences (GAS elements) near the interferon-gamma gene and stimulate
      its transcription. The amino-terminal domain of STAT4 (STAT4(1-124)) is required
      for cooperative binding interactions between STAT4 dimers and activation of
      interferon-gamma transcription in response to interleukin-12. We have
      overproduced this domain of human STAT4 (hSTAT4(1-124)) in Escherichia coli and
      purified it to homogeneity for structural studies. The circular dichroism
      spectrum of hSTAT4(1-124) indicates that it has a well ordered conformation in
      solution. The translational diffusion constant of hSTAT4(1-124) was determined by
      nuclear magnetic resonance methods and found to be consistent with that of a
      dimer. The rotational correlation time (tauc) of hSTAT4(1-124) was estimated from
      15N relaxation to be 16 ns; this value is consistent with a 29-kDa dimeric
      protein. These results, together with the number of signals observed in the two
      dimensional 1H-15N heteronuclear single quantum coherence spectrum of uniformly
      15N-labeled protein, indicate that hSTAT4(1-124) forms a stable, symmetric
      homodimer in solution. Cooperativity in native STAT4 probably results from a
      similar or identical interaction between the amino-terminal domains of adjacent
      dimers bound to DNA.

PMID- 9642278
TI  - Phosphatidylinositol 4-phosphate synthesis in immunoisolated caveolae-like
      vesicles and low buoyant density non-caveolar membranes.
AB  - This study examined phosphatidylinositol 4-phosphate (PtdIns4P) synthesis in
      caveolae that have been suggested to be discrete signaling microdomains of the
      plasma membrane and are enriched in the marker protein caveolin. Caveolin-rich
      light membranes (CLMs) were isolated from A431 cells by detergent-free,
      discontinuous density-gradient centrifugation method. The CLM fraction was
      separated from the bulk of the cellular protein and was greatly enriched in
      PtdIns, PtdIns4P, and phosphatidylinositol 4, 5-bisphosphate (PtdIns(4,5)P2) and
      an adenosine-sensitive type II PtdIns 4-kinase activity. Preparation of CLMs by
      an OptiPrep-based cell fractionation procedure confirmed the co-localization of
      PtdIns 4-kinase and caveolin. Electron microscopy confirmed that an anti-caveolin
      antiserum immunopurified vesicles from CLMs that were within the size range
      described for caveolae in other systems. Co-immunoprecipitated PtdIns 4-kinase
      activity could utilize endogenous PtdIns, present within the caveolae-like
      vesicles, to produce PtdIns4P. The addition of recombinant phosphatidylinositol
      transfer protein increased PtdIns 4-kinase activity both in immunoisolated
      caveolae and CLMs. However, less than 1% of the total cellular PtdIns and PtdIns
      4-kinase activity was present in caveolae-like vesicles, indicating that non
      caveolar light membrane rafts are the main site for cellular PtdIns4P production.

PMID- 9642279
TI  - The fragile-X-related gene FXR1 is a human autoantigen processed during
      apoptosis.
AB  - We describe a new human autoimmune antigen in a patient suffering from
      scleroderma with high levels of antibodies to nucleolus and cytoplasmic antigens.
      Using a Chinese hamster ovary cell expression library, we have shown that this
      antigen corresponds to the autosomal Fragile-X-related gene FXR1. The deduced
      amino acid sequence from the hamster cDNA is 97, 98, and 58% homologous to the
      human, mouse, and Xenopus laevis FXR1 genes, respectively. Expression of the
      hamster cDNA clone in Escherichia coli and antibody production indicates
      unequivocally the location of the FXR1 protein in the cytoplasm of hamster cells.
      Affinity chromatography followed by immunofluorescence microscopy analysis and
      immunoblots demonstrated the presence of autoimmune IgGs to FXR1 in the
      scleroderma patient. Immunolabeling studies in Jurkat cells, induced to apoptosis
      by anti-Fas/APO1 serum, indicated that the FXR1 antigens were clearly displaced
      from their original cytoplasmic location to several punctuated foci, resembling
      the bleb-like membranous structures characteristic of cells at certain stages of
      apoptosis. This phenomenon could be part of a putative mechanism in which the
      FXR1 protein is presented as a target for the autoimmune response in humans.

PMID- 9642280
TI  - Colony-stimulating factor-1 stimulates the formation of multimeric cytosolic
      complexes of signaling proteins and cytoskeletal components in macrophages.
AB  - Stimulation of macrophages with colony-stimulating factor-1 (CSF-1) results in
      the protein tyrosine phosphorylation of the CSF-1 receptor (CSF-1R) and many
      other, primarily cytosolic, proteins. Stimulation by CSF-1 at 4 degreesC was used
      to facilitate the purification and identification of the proteins of the
      cytosolic anti-phosphotyrosine (PY)-reactive fraction (alphaPY-RF) involved in
      downstream signaling pathways. Confocal microscopy revealed that the PY proteins
      are in close proximity to the CSF-1R at the plasma membrane. The alphaPY-RF
      contained pre-existing complexes of PY proteins and non-PY proteins which
      generally increased in size and PY protein content following CSF-1 stimulation.
      PY proteins identified by microsequencing and Western blotting include Cbl,
      STAT3, STAT5a, STAT5b, SHP-1, Shc, and two novel proteins pp57 and pp37. Other
      proteins included cytoskeletal/contractile proteins (paxillin, vimentin,
      elongation factor-1alpha, F-actin, tropomyosin, and myosin regulatory light
      chain), Ras family signaling proteins (p85 (phosphoinositide 3-kinase), Vav, Ras
      GTPase-activating protein SH3 domain-binding protein, and Grb2), DnaJ-like
      protein, and glyceraldehyde-3-phosphate dehydrogenase. CSF-1 induced the de novo
      recruitment of Cbl, STAT3, STAT5a, STAT5b, p85, SHP-1, Shc, vimentin, and Grb2 to
      complexes and caused pre-existing complexes involving Vav, elongation factor
      1alpha, and F-actin to increase in size. These studies indicate that CSF-1
      induced protein tyrosine phosphorylation is associated with the reorganization of
      complexes of cytoskeletal, signaling, and other proteins that mediate CSF-1
      regulated motility and growth.

PMID- 9642281
TI  - Estrogen response elements can mediate agonist activity of anti-estrogens in
      human endometrial Ishikawa cells.
AB  - Anti-estrogens like hydroxytamoxifen (OHT) have mixed agonist/antagonist
      activities, leading to tissue-specific stimulation of cellular proliferation.
      Partial agonist activity of OHT can be observed in vitro in endometrial carcinoma
      cells like Ishikawa. Here, we have compared several anti-estrogens (including
      extensively characterized OHT and pure anti-estrogens such as ICI164, 384 and
      RU58,668, which are devoid of uterotrophic activity) for their capacity to
      stimulate promoters containing estrogen response elements (EREs) or AP1-binding
      sites (12-O-tetradecanoylphorbol-13-acetate response elements, TREs), the two
      types of DNA motifs known to mediate transcriptional stimulation by estrogen
      receptors. Assays were performed in Ishikawa cells either by transient
      transfection or by using cell lines with stably propagated reporter vectors. In
      transient transfection experiments, none of the anti-estrogens displayed agonist
      activity on the promoters tested. In contrast, significant transcriptional
      stimulation was observed with low concentrations of OHT and RU39,411 in Ishikawa
      cells stably propagating reporter constructs containing a minimal ERE3-TATA
      promoter. In addition, micromolar concentrations of OHT, but not of RU39,411,
      stimulated stably propagated AP1-responsive reporter constructs. No
      transcriptional stimulation of ERE- or TRE-containing promoters was observed with
      the pure anti-estrogens ICI164,384 and RU58,668. These results indicate that the
      presence of estrogen response elements in promoters is sufficient to mediate cell
      specific agonism of anti-estrogens at the transcriptional level, and that
      stimulation of AP1 activity may be restricted to a subset of anti-estrogens
      possessing agonist activity on EREs. In addition, our results suggest that
      transient transfections do not fully recapitulate in vivo conditions required to
      observe agonist activity of anti-estrogens.

PMID- 9642282
TI  - Heat shock protein 72 modulates pathways of stress-induced apoptosis.
AB  - The resistance to stress-induced apoptosis conferred by the thermotolerant state
      or by exogenous expression of HSP72 was measured in mouse embryo fibroblasts. The
      induction of thermotolerance protects cells from heat, tumor necrosis factor
      alpha (TNFalpha), and ceramide-induced apoptosis but not from ionizing radiation.
      Because the development of thermotolerance is associated with increased levels of
      heat shock proteins, we determined whether constitutive expression of one of the
      major inducible heat shock proteins, HSP72, could also protect cells from stress
      induced apoptosis. Cells expressing constitutive HSP72 were shown to have
      significantly reduced levels of apoptosis after heat, TNFalpha, and ceramide but
      not after ionizing radiation. Activation of stress-activated protein kinase/c-Jun
      N-terminal kinase (SAPK/JNK) was found to be strongly inhibited in thermotolerant
      cells after heat shock but not after other stresses. Cells that constitutively
      express HSP72 did not demonstrate decreased SAPK/JNK activation after any of
      these stresses. Thus, factors other than HSP72 that are induced in the
      thermotolerant state are able to reduce activation of SAPK/JNK after heat stress.
      Notably, the level of activation of SAPK/JNK did not correlate with the amount of
      apoptosis detected after different stresses. Constitutive HSP72 expression
      inhibited poly(ADP-ribose) polymerase cleavage in cells after heat shock and
      TNFalpha but not after ceramide or ionizing radiation. The results suggest either
      that SAPK/JNK activation is not required for apoptosis in mouse embryo
      fibroblasts or that HSP72 acts downstream of SAPK/JNK. Furthermore, the data
      support the concept that caspase activity, which can be down-regulated by HSP72,
      is a crucial step in stress-induced apoptosis. Based on data presented here and
      elsewhere, we propose that the heat shock protein family can be classified as a
      class of anti-apoptotic genes, in addition to the Bcl-2 and inhibitor of
      apoptosis protein families of genes.

PMID- 9642283
TI  - In vitro reconstitution of the recombinant photosystem II light-harvesting
      complex CP24 and its spectroscopic characterization.
AB  - The light-harvesting chlorophyll a/b protein CP24, a minor subunit of the
      photosystem II antenna system, is a major violaxanthin-binding protein involved
      in the regulation of excited state concentration of chlorophyll a. This subunit
      is poorly characterized due to the difficulty in isolation and instability during
      purification procedures. We have used an alternative approach in order to gain
      information on the properties of this protein; the Lhcb6 cDNA has been
      overexpressed in bacteria in order to obtain the CP24 apoprotein, which was then
      reconstituted in vitro with xanthophylls, chlorophyll a, and chlorophyll b,
      yielding a pigment-protein complex with properties essentially identical to the
      native protein extracted from maize thylakoids. Although all carotenoids were
      supplied during refolding, the recombinant holoprotein exhibited high selectivity
      in xanthophyll binding by coordinating violaxanthin and lutein but not neoxanthin
      or beta-carotene. Each monomer bound a total of 10 chlorophyll a plus chlorophyll
      b and two xanthophyll molecules. Moreover, the protein could be refolded in the
      presence of different chlorophyll a to chlorophyll b ratios for yielding a family
      of recombinant proteins with different chlorophyll a/b ratios but still binding
      the same total number of porphyrins. A peculiar feature of CP24 was its refolding
      capability in the absence of lutein, contrary to the case of other homologous
      proteins, thus showing higher plasticity in xanthophyll binding. These
      characteristics of CP24 are discussed with respect to its role in binding
      zeaxanthin in high light stress conditions. The spectroscopic analysis of a
      recombinant CP24 complex binding eight chlorophyll b molecules and a single
      chlorophyll a molecule by Gaussian deconvolution allowed the identification of
      four subbands peaking at wavelengths of 638, 645, 653, and 659 nm, which have an
      increased amplitude with respect to the native complex and therefore identify the
      chlorophyll b absorption in the antenna protein environment. Gaussian subbands at
      wavelengths 666, 673, 679, and 686 nm are depleted in the high chlorophyll b
      complex, thus suggesting they derive from chlorophyll a.

PMID- 9642284
TI  - Regulation of a TATA-binding protein-associated factor during cellular
      differentiation.
AB  - RNA polymerase III transcription is down-regulated when F9 embryonal carcinoma
      cells differentiate into parietal endoderm. This reflects a decrease in the
      activity of TFIIIB, a multisubunit complex that is required for all class III
      gene expression. Two essential components of TFIIIB are the TATA-binding protein
      (TBP) and an associated polypeptide called BRF that is specific to this complex.
      The abundance of both TBP and BRF decreases during F9 cell differentiation.
      Whereas the amount of TBP assembled into TFIIIB is down-regulated, this is not
      the case for all TBP-containing complexes. BRF levels show a more dramatic
      decline that appears sufficient to account for the overall change in
      transcriptional activity. Developmental regulation of a specific class of genes
      may therefore be achieved through changes in the availability of a TBP-associated
      factor.

PMID- 9642285
TI  - The human interferon-inducible protein, IFI 16, is a repressor of transcription.
AB  - IFI 16 is a member of a family of interferon-inducible proteins, including the
      human MNDA (myeloid nuclear differentiation antigen), the recently identified AIM
      2 (absent in melanoma), and the homologous murine molecules, p202, p204, and D3.
      IFI 16 contains a domain at the amino terminus capable of binding double-stranded
      DNA and a bipartite nuclear localization signal. No molecular or biological
      function has been assigned to any of the human family members, although a role in
      transcription regulation has been proposed. In the present study, we show IFI 16
      fused to the GAL4 DNA binding domain can function as a transcriptional repressor.
      IFI 16-mediated repression is not dependent on the position or distance of IFI 16
      binding, relative to the site of transcription initiation, and it can
      significantly repress when only one GAL4 DNA element is present in the promoter.
      We mapped the transcriptional repression domains to the 200 amino acid repeat
      regions common to all human and mouse family members. We also demonstrate that
      wild type IFI 16 can repress transcription of a reporter gene containing the
      minimal promoter region of the human cytomegalovirus UL54 gene. Thus, IFI 16 is a
      transcriptional repressor, with a modular structure typical of many known
      transcription regulators.

PMID- 9642286
TI  - Arrangement of the multicopy H+-translocating subunit c in the membrane sector of
      the Escherichia coli F1F0 ATP synthase.
AB  - The multicopy subunit c of the H+-transporting F1F0 ATP synthase of Escherichia
      coli is thought to fold across the membrane as a hairpin of two hydrophobic alpha
      helices. The conserved Asp61, centered in the second transmembrane helix, is
      essential for H+ transport. In this study, we have made sequential Cys
      substitutions across both transmembrane helices and used disulfide cross-link
      formation to determine the oligomeric arrangement of the c subunits. Cross-link
      formation between single Cys substitutions in helix 1 provided initial
      limitations on how the subunits could be arranged. Double Cys substitutions at
      positions 14/16, 16/18, and 21/23 in helix 1 and 70/72 in helix 2 led to the
      formation of cross-linked multimers upon oxidation. Double Cys substitutions in
      helix 1 and helix 2, at residues 14/72, 21/65, and 20/66, respectively, also
      formed cross-linked multimers. These results indicate that at least 10 and
      probably 12 subunits c interact in a front-to-back fashion to form a ring-like
      arrangement in F0. Helix 1 packs at the interior and helix 2 at the periphery of
      the ring. The model indicates that the Asp61 carboxylate is centered between the
      helical faces of adjacent subunit c at the center of a four-helix bundle.

PMID- 9642287
TI  - Phosphorylation of CrkII adaptor protein at tyrosine 221 by epidermal growth
      factor receptor.
AB  - CrkII adaptor protein becomes tyrosine-phosphorylated upon various types of
      stimulation. We examined whether tyrosine 221, which has been shown to be
      phosphorylated by c-Abl, was phosphorylated also by other tyrosine kinases, such
      as epidermal growth factor (EGF) receptor. For this purpose, we developed an
      antibody that specifically recognizes Tyr221-phosphorylated CrkII, and we
      demonstrated that CrkII was phosphorylated on Tyr221 upon EGF stimulation. When
      NRK cells were stimulated with EGF, the tyrosine-phosphorylated CrkII was
      detected at the periphery of the cells, where ruffling is prominent, suggesting
      that signaling to CrkII may be involved in EGF-dependent cytoskeletal
      reorganization. The EGF-dependent phosphorylation of CrkII was also detected in a
      c-Abl-deficient cell line. Moreover, recombinant CrkII protein was phosphorylated
      in vitro by EGF receptor. These results strongly suggest that EGF receptor
      directly phosphorylates CrkII. Mutational analysis revealed that the src homology
      2 domain was essential for the phosphorylation of CrkII by EGF receptor but not
      by c-Abl, arguing that these kinases phosphorylate CrkII by different
      phosphorylation mechanisms. Finally, we found that the CrkII protein
      phosphorylated upon EGF stimulation did not bind to the phosphotyrosine
      containing peptide and that CrkII initiated dissociation from EGF receptor within
      3 min even with the sustained tyrosine phosphorylation of EGF receptor. This
      result implicated phosphorylation of Tyr221 in the negative regulation of the src
      homology 2-mediated binding of CrkII to EGF receptor.

PMID- 9642288
TI  - Porcine spleen deoxyribonuclease II. Covalent structure, cDNA sequence, molecular
      cloning, and gene expression.
AB  - Porcine spleen DNase II, a lysosomal acid hydrolase, is a noncovalently linked
      alpha.beta heterodimer (Liao, T.-H. (1985) J. Biol. Chem. 260, 10708-10713). The
      alpha subunit, after disulfide cleavage, yields two chains, alpha1 and alpha2.
      The complete amino acid sequences of the alpha1, beta, and alpha2 chains were
      elucidated by protein sequencing, and the pairings of one interchain disulfide
      between alpha1 and alpha2 and of three intrachain disulfides in alpha2 were
      assigned. Six carbohydrate attachment sites, two in beta and four in alpha2, were
      detected by sugar analyses. The cDNA of DNase II was amplified using primers
      synthesized on the basis of the amino acid sequences determined. The amplified
      fragments shown to be a cDNA sequence of 1,292 bases. This cDNA sequence has an
      open reading frame encoding a 364-amino acid polypeptide containing a putative
      transmembrane peptide at the NH2-end, two small connecting peptides in the
      middle, and a peptide at the COOH terminus. These are evidently removed to form
      mature DNase II. Thus, all three chains in the sequence alpha1, beta, and alpha2
      are coded by the same cDNA. When Chinese hamster ovary cells were transfected
      with a cloned plasmid with an inserted cDNA fragment encoding the entire reading
      frame, the expressed protein was released into the growth medium as an active
      form of DNase II.

PMID- 9642289
TI  - Genetic evidence that phosphatidylserine synthase II catalyzes the conversion of
      phosphatidylethanolamine to phosphatidylserine in Chinese hamster ovary cells.
AB  - Phosphatidylserine (PS) in mammalian cells is synthesized through the exchange of
      free L-serine with the base moiety of phosphatidylcholine or
      phosphatidylethanolamine (PE). The serine base exchange in Chinese hamster ovary
      (CHO) cells is catalyzed by at least two enzymes, PS synthase (PSS) I and II. A
      PSS I-lacking mutant of CHO-K1 cells, PSA-3, which exhibits approximately 2-fold
      lower serine base exchange activity than CHO-K1, is defective in the conversion
      of phosphatidylcholine to PS but has the ability to convert PE to PS. The PSA-3
      mutant requires exogenous PS or PE for cell growth. In the present study, from
      PSA-3 mutant cells, we isolated a mutant, named PSB-2, with a further decrease in
      the serine base exchange activity. The activity in the homogenate of PSB-2 mutant
      cells was approximately 10% that of PSA-3 mutant cells and approximately 5% that
      of CHO-K1 cells. The PSB-2 mutant exhibited an approximately 80% reduction in the
      PSS II mRNA level relative to that in PSA-3 mutant and CHO-K1 cells. These
      results showed that the PSB-2 mutant is defective in PSS II. Like the PSA-3
      mutant, the PSB-2 mutant grew well in medium supplemented with PS. However, in
      the medium supplemented with PE, the PSB-2 mutant was incapable of growth, in
      contrast to the PSA-3 mutant. In the medium with exogenous PE, the PSB-2 mutant
      was defective in PS biosynthesis, whereas the PSA-3 mutant synthesized a normal
      amount of PS. A metabolic labeling experiment with exogenous [32P]PE revealed
      that the PSB-2 mutant was defective in the conversion of exogenous PE to PS. This
      defect and the growth and PS biosynthetic defects of the PSB-2 mutant cultivated
      with exogenous PE were complemented by the PSS II cDNA. In addition, the cDNA of
      the other PS synthase, PSS I, was shown not to complement the defect in the
      conversion of exogenous PE to PS of the PSB-2 mutant, implying that PSS I
      negligibly contributes to the conversion of PE to PS in CHO-K1 cells. These
      results indicated that PSS II is critical for the growth and PS biosynthesis of
      PSA-3 mutant cells cultivated with exogenous PE and suggested that most of the PS
      formation from PE in CHO-K1 cells is catalyzed by PSS II.

PMID- 9642290
TI  - Regulation of expression within a gene family. The case of the rat gammaB- and
      gammaD-crystallin promoters.
AB  - The six closely related and clustered rat gamma-crystallin genes, the gammaA- to
      gammaF-crystallin genes, are simultaneously activated in the embryonic lens but
      differentially shut down during postnatal development with the gammaB-crystallin
      gene, the last one to be active. We show here that developmental silencing of the
      gammaD-crystallin promoter correlates with delayed demethylation during lens
      fiber cell differentiation. Methylation silencing of the gammaD-crystallin
      promoter is a general effect and does not require the methylation of a specific
      CpG, nor does methylation interfere with factor binding to the proximal
      activator. In later development, the gammaD-crystallin promoter is also shut down
      earlier by a repressor that footprints to the -91/-78 region. A factor with
      identical properties is present in brain. Hence, a ubiquitous factor has been
      recruited as a developmental regulator by the lens. All gamma-crystallin
      promoters tested contain upstream silencers, but at least the gammaB-crystallin
      silencer is distinct from the gammaD-crystallin silencer. The gamma-crystallin
      promoters were found to share a proximal activator (the gamma-box; around -50),
      which behaves as a MARE. The gammaB-box is recognized with much lower avidity
      than the gammaD-box. By swapping elements between the gammaB- and the gammaD
      crystallin promoter, we show that activation by the gammaB-box requires a
      directly adjacent -46/-38 AP-1 consensus site. These experiments also uncovered
      another positive element in the gammaD-crystallin promoter, around -10. In the
      context of the gammaD-crystallin promoter, this element is redundant; in the
      context of the gammaB-crystallin promoter, it can replace the -46/-38 element.

PMID- 9642291
TI  - A new class of DNA glycosylase/apurinic/apyrimidinic lyases that act on specific
      adenines in single-stranded DNA.
AB  - Although the biological function of DNA glycosylases is to protect the genome by
      removal of potentially cytotoxic or mutagenic bases, this investigation describes
      the existence of natural DNA glycosylases with activity on undamaged,
      nonmispaired bases. Gelonin, pokeweed antiviral protein, and ricin, previously
      described as ribosome-inactivating proteins, are shown to damage single-stranded
      DNA by removal of a protein-specific set of adenines and cleavage at the
      resulting abasic sites. Using an oligonucleotide as the substrate reveals that
      the reaction proceeds via the enzyme-DNA imino intermediate characteristic of DNA
      glycosylase/AP lyases. The adenine glycosylase activity on single-stranded DNA
      reported here challenges the concept that a normal base has to be in a mismatch
      to be specifically removed. By contrast to other glycosylases, these enzymes are
      expected to damage DNA rather than participate in repair processes. The
      significance of this DNase activity to the biological function of these plant
      proteins and to their toxicity to animal cells remains to be determined.

PMID- 9642292
TI  - Oligomeric nature of the integral membrane protein stomatin.
AB  - The 31-kDa integral membrane protein stomatin (protein 7.2b) is not only an
      important component of the red cell membrane but can also be found in abundance
      in different tissues and cell lines. The protein is thought to be anchored to the
      membrane by a hydrophobic domain while both N and C termini are exposed to the
      cytoplasm. We have previously shown in the human cell line UAC that stomatin
      concentrates preferentially in plasma membrane folds and protrusions. There is
      also evidence that stomatin is linked to the cortical actin cytoskeleton,
      suggesting a role in cortical morphogenesis of the cell. In this study, we
      demonstrate that the fundamental structure of stomatin is oligomeric. Whereas
      interaction of stomatin with itself was suggested by cross-linking experiments,
      we show by density gradient centrifugation analysis that soluble homo-oligomeric
      complexes of this protein are present in Triton X-100 extracts of UAC cells. We
      also show the existence of these oligomers by co-immunoprecipitation of the
      endogenous stomatin and a recombinantly expressed myc-tagged stomatin, using an
      anti-myc antibody. The data indicate that these complexes comprise between 9 and
      12 monomers of stomatin. Two C-terminally truncated forms of stomatin do not
      incorporate into these oligomers, suggesting an involvement of the C terminus in
      the homo-oligomeric interaction.

PMID- 9642293
TI  - Conserved in vivo phosphorylation of calnexin at casein kinase II sites as well
      as a protein kinase C/proline-directed kinase site.
AB  - Calnexin is a lectin-like chaperone of the endoplasmic reticulum (ER) that
      couples temporally and spatially N-linked oligosaccharide modifications with the
      productive folding of newly synthesized glycoproteins. Calnexin was originally
      identified as a major type I integral membrane protein substrate of kinase(s)
      associated with the ER. Casein kinase II (CK2) was subsequently identified as an
      ER-associated kinase responsible for the in vitro phosphorylation of calnexin in
      microsomes (Ou, W-J., Thomas, D. Y., Bell, A. W., and Bergeron, J. J. M. (1992)
      J. Biol. Chem. 267, 23789-23796). We now report on the in vivo sites of calnexin
      phosphorylation. After 32PO4 labeling of HepG2 and Madin-Darby canine kidney
      cells, immunoprecipitated calnexin was phosphorylated exclusively on serine
      residues. Using nonradiolabeled cells, we subjected calnexin immunoprecipitates
      to in gel tryptic digestion followed by nanoelectrospray mass spectrometry
      employing selective scans specific for detection of phosphorylated fragments.
      Mass analyses identified three phosphorylated sites in calnexin from either HepG2
      or Madin-Darby canine kidney cells. The three sites were localized to the more
      carboxyl-terminal half of the cytosolic domain: S534DAE (CK2 motif), S544QEE (CK2
      motif), and S563PR. We conclude that CK2 is a kinase that phosphorylates calnexin
      in vivo as well as in microsomes in vitro. Another yet to be identified kinase
      (protein kinase C and/or proline-directed kinase) is directed toward the most
      COOH-terminal serine residue. Elucidation of the signaling cascade responsible
      for calnexin phosphorylation at these sites in vivo may define a novel regulatory
      function for calnexin in cargo folding and transport to the ER exit sites.

PMID- 9642294
TI  - The effects of chaperones and the influence of protein assembly on peroxisomal
      protein import.
AB  - Peroxisomal proteins are synthesized in the cytoplasm and post-translationally
      translocated into the organelle. The role of chaperones and protein folding in
      peroxisomal protein transport is still unclear. Translocation of proteins into
      mitochondria requires that precursor proteins assume an extended conformation;
      cytosolic chaperones are thought to help maintain this conformation. In contrast,
      peroxisomal protein import does not require unfolding of the targeted protein.
      However, the molecular chaperones Hsp70 and Hsp40 may be important for
      translocation. We present several lines of evidence that show that plant
      peroxisomal protein import is enhanced by chaperones. First, peroxisomes isolated
      from heat-shocked pumpkin seedling tissues exhibited increased protein import
      relative to control peroxisomes. Second, antibodies raised against wheat germ
      cytosolic Hsp70 and Escherichia coli Hsp90 inhibited import of the peroxisomal
      protein isocitrate lyase. To our knowledge, this is the first time that Hsp90 has
      been directly implicated in a protein transport event. Third, peroxisomal
      proteins were immunoprecipitated by wheat germ Hsp70 antibodies. We also present
      results that suggest that the efficiency of peroxisomal protein import is
      influenced by the structure of the targeted protein; monomeric isocitrate lyase
      was imported more efficiently than oligomeric isocitrate lyase. Taken together,
      these data demonstrate that the assembly state of peroxisomal proteins and the
      chaperones that may mediate those states are both important for efficient
      peroxisomal protein import.

PMID- 9642295
TI  - Topology of SREBP cleavage-activating protein, a polytopic membrane protein with
      a sterol-sensing domain.
AB  - The NH2-terminal fragments of sterol regulatory element-binding proteins (SREBPs)
      are released from endoplasmic reticulum membranes by proteases whose activities
      depend upon SREBP cleavage-activating protein (SCAP), a polytopic endoplasmic
      reticulum membrane protein. The activity of SCAP is inhibited by sterols, which
      appear to interact with the polytopic membrane domain of SCAP. Here, we use
      protease protection and N-linked glycosylation site-mapping techniques to define
      the topology of the eight membrane-spanning domains of SCAP. The data indicate
      that the NH2 terminus and COOH terminus of SCAP face the cytosol. The long
      intralumenal loops after membrane-spanning segments 1 and 7 are glycosylated,
      confirming their lumenal location. The region comprising membrane-spanning
      segments 2-6 shows sequence resemblance to putative sterol-sensing domains in
      three other proteins: 3-hydroxy-3-methylglutaryl CoA reductase (HMG-CoA
      reductase), the Niemann-Pick C1 protein, and the morphogen receptor Patched. The
      orientation of the eight membrane-spanning segments in SCAP is consistent with
      the model proposed for HMG-CoA reductase (Olender, E. H., and Simoni, R. D.
      (1992) J. Biol. Chem. 267, 4223-4235). The membrane-spanning domains of SCAP and
      HMG-CoA reductase confer sterol sensitivity upon the functional activities of the
      two molecules. The common membrane topology of the two proteins is consistent
      with the notion that sterols regulate both proteins by a common mechanism.

PMID- 9642296
TI  - Unique composition of the preprotein translocase of the outer mitochondrial
      membrane from plants.
AB  - Transport of most nuclear encoded mitochondrial proteins into mitochondria is
      mediated by heteropolymeric translocases in the membranes of the organelles. The
      translocase of the outer mitochondrial membrane (TOM) was characterized in fungi,
      and it was shown that TOM from yeast comprises nine different subunits. This
      publication is the first report on the preparation of the TOM complex from plant
      mitochondria. The protein complex from potato was purified by (a) blue native
      polyacrylamide gel electrophoresis and (b) by immunoaffinity chromatography. On
      blue native gels, the potato TOM complex runs close to cytochrome c oxidase at
      230 kDa and hence only comprises about half of the size of fungal TOM complexes.
      Analysis of the TOM complex from potato by SDS-polyacrylamide gel electrophoresis
      allows separation of seven different subunits of 70, 36, 23, 9, 8, 7, and 6 kDa.
      The 23-kDa protein is identical to the previously characterized potato TOM20
      receptor, as shown by in vitro assembly of this protein into the 230-kDa complex,
      by immunoblotting and by direct protein sequencing. Partial amino acid sequence
      data of the other subunits allowed us to identify sequence similarity between the
      36-kDa protein and fungal TOM40. Sequence analysis of cDNAs encoding the 7-kDa
      protein revealed significant sequence homology of this protein to TOM7 from
      yeast. However, potato TOM7 has a N-terminal extension, which is very rich in
      basic amino acids. Counterparts to the TOM22 and TOM37 proteins from yeast seem
      to be absent in the potato TOM complex, whereas an additional low molecular mass
      subunit occurs. Functional implications of these findings are discussed.

PMID- 9642297
TI  - Cell surface ectodomain cleavage of human amphiregulin precursor is sensitive to
      a metalloprotease inhibitor. Release of a predominant N-glycosylated 43-kDa
      soluble form.
AB  - Biosynthesis and processing of amphiregulin (AR) have been investigated in human
      colorectal (HCA-7, Caco-2) and mammary (MCF-7) cancer cell lines, as well as in
      Madin-Darby canine kidney cells stably expressing various human AR precursor (pro
      AR) forms. Both cells expressing endogenous and transfected AR produce multiple
      cellular and soluble forms of AR with an N-glycosylated 50-kDa pro-AR form being
      predominant. Our results demonstrate that sequential proteolytic cleavage within
      the ectodomain of the 50-kDa pro-AR form leads to release of a predominant N
      glycosylated 43-kDa soluble AR, as well as the appearance of other cellular and
      soluble AR forms. Cell surface biotinylation studies using a C-terminal epitope
      tagged pro-AR indicate that all cell surface forms are membrane-anchored and
      support that AR is released by ectodomain cleavage of pro-AR at the plasma
      membrane. We also show that pro-AR ectodomain cleavage is a regulated process,
      which can be stimulated by phorbol 12-myristate 13-acetate and inhibited by the
      metalloprotease inhibitor, batimastat. In addition, we provide evidence that high
      molecular mass AR forms may retain the full-length N-terminal pro-region, which
      may influence the biological activities of these forms.

PMID- 9642298
TI  - Rab2 protein enhances coatomer recruitment to pre-Golgi intermediates.
AB  - The Rab2 protein is a resident of pre-Golgi intermediates and required for
      vesicular transport in the early secretory pathway. We have previously shown that
      a peptide corresponding to the amino terminus of Rab2 (residues 2-14) arrests
      protein traffic prior to a rate-limiting event in VSV-G movement through pre
      Golgi structures (Tisdale, E. J., and Balch, W. E. (1996) J. Biol. Chem. 271,
      29372-29379). To determine the mechanism by which this peptide inhibits
      transport, we investigated the effect of the Rab2 peptide on the distribution of
      the beta-COP subunit of coatomer because COPI partially localizes to pre-Golgi
      intermediates. We found that the peptide caused a dramatic change in the
      distribution of pre-Golgi intermediates containing beta-COP. A quantitative
      binding assay was employed to measure recruitment of beta-COP to membrane when
      incubated with the Rab2 (13-mer). Peptide-treated microsomes showed a 25-70%
      increase in the level of membrane-associated beta-COP. The enhanced recruitment
      of coatomer to membrane was specific to the Rab2 (13-mer) and required guanosine
      5'-3-O-(thio)triphosphate, ADP ribosylation factor, and protein kinase C-like
      activity. The ability to enhance beta-COP membrane binding was not limited to the
      peptide. Similarly, the addition of recombinant Rab2 protein to the assay
      promoted beta-COP membrane association. Our results suggest that the Rab2 peptide
      causes the persistent recruitment of COPI to pre-Golgi intermediates which
      ultimately arrests protein transport due to the inability of membranes to uncoat.

PMID- 9642299
TI  - Ribosome binding to mitochondria is regulated by GTP and the transit peptide.
AB  - The association between ribosomes and the pore proteins at the endoplasmic
      reticulum membrane is important to co-translational translocation. To determine
      if a similar association occurs between the ribosome and mitochondrial membrane
      protein(s) during protein import in higher eukaryotes, we examined ribosome
      mitochondria binding. By using spectral measurements, analysis of mitochondrial
      associated RNA, and electron microscopy, we demonstrated that ribosomes stably
      bind to purified rat liver mitochondria in vitro. Binding of ribosomes to
      mitochondria was markedly reduced by GTP and nearly abolished by the non
      hydrolyzable GTP analogue, guanosine-5'-[thio]-triphosphate (GTPgammaS), but was
      only modestly reduced by GDP or ATP and unaffected by CTP. The initial rate of
      GTP hydrolysis by mitochondria was increased by ribosomes, whereas the rate of
      ATP hydrolysis by mitochondria was not affected. Ribosomes programmed with mRNA
      for 92 amino acids of the N terminus of mitochondrial malate dehydrogenase bound
      to mitochondria, but unlike unprogrammed rat liver ribosomes, neither GTP nor GDP
      disrupted binding; however, GTPgammaS did. These data show that receptors
      specific for ribosomes are present on the mitochondrial membrane, and a GTP
      dependent process mediates this binding. The presence of a nascent chain alters
      these binding characteristics. These findings support the hypothesis that a co
      translational translocation pathway exists for import of proteins into
      mitochondria.

PMID- 9642300
TI  - The gene encoding human nuclear protein tyrosine phosphatase, PRL-1. Cloning,
      chromosomal localization, and identification of an intron enhancer.
AB  - Expression of the rat PRL-1 gene, which encodes a unique nuclear protein tyrosine
      phosphatase, is positively associated with cellular growth during liver
      development, regeneration, and oncogenesis but with differentiation in intestine
      and other tissues. Here, we analyzed the structure of the human PRL-1 gene and
      localized it to chromosome 6 within band q12. Human, rat, and mouse PRL-1 are
      100% conserved at the amino acid level and 55% identical to a newly identified
      Caenorhabditis elegans PRL-1. The presence of two promoter activities, P1 and P2,
      in the human PRL-1 gene were identified by primer extension and RNase protection
      assays. A functional TATA box was identified in promoter P1 upstream of the non
      coding first exon. A non-canonical internal promoter, P2, was found in the first
      intron that results in PRL-1 transcripts beginning 8 base pairs downstream of the
      5'-end of exon 2 and causes no alteration in the encoded protein. The first 200
      base pair region of either promoter P1 or P2 conferred high basal transcriptional
      activity. An enhancer that bound a developmentally regulated factor, PRL-1 intron
      enhancer complex (PIEC), was localized to the first intron of the human PRL-1
      gene. The presence of PIEC correlated with the ability of the intron enhancer to
      confer transcriptional activation in HepG2 and F9 cells. The intron enhancer
      contributed significantly to PRL-1 promoter activity in HepG2 cells which contain
      PIEC but not to NIH 3T3 cells which do not.

PMID- 9642301
TI  - New frontiers in physiology of presby-cardia.

PMID- 9642302
TI  - The use of gonadotrophin-releasing hormone analogues in gynaecology.

PMID- 9642303
TI  - Comparative study of effects of three kinds of herbal mixture decoctions on
      improving immune senescence and free radical metabolism.
AB  - OBJECTIVE: To verify from the aspects of immune senescence and free radical
      metabolism that "removing blood stasis as well as tonifying kidney is an ideal
      way to delay aging" and further investigate the anti-aging mechanism of this
      therapy. METHODS: In the first period, the old mice were separately fed with the
      herbal decoction of the recipe of tonifying kidney, or of removing blood stasis,
      or of tonifying kidney and removing blood stasis for four weeks, and then IL-2
      production of splenic lymphocytes, IL-1 production of peritoneal macrophages,
      SOD, CAT and GSH-Px activity in erythrocytes, and LPO contents in liver and brain
      were compared between the young control group and the old control group, or the
      old control group and each of the old medication groups. In the second period,
      the adult mice inhaled ozone or the splenic lymphocytes from adult mice were
      cultured in the medium containing peroxide hydrogen. The effects of free radicals
      on immune system and the reversion of the herbal decoction of the recipe of
      removing blood stasis as well as tonifying kidney were observed. RESULTS: The
      activities of IL-1, IL-2, SOD, CAT and GSH-PX in old mice were significantly
      lower than those in young mice, and LPO contents were higher. The three herbal
      decoctions all have reversing effects on each of these parameters except that the
      decoction of removing blood stasis has inhibitory effects on IL-1 and IL-2
      production. The effect of the decoction of removing blood stasis as well as
      tonifying kidney was the best among the three decoctions, and it can also reverse
      the impaired production of IL-2 by ozone in vivo and peroxide hydrogen in vitro.
      CONCLUSIONS: The therapeutic method of removing blood stasis as well as tonifying
      kidney is an ideal way to delay aging, and its effects to improve immune
      senescence is correlated with the decrease of free radical damages.

PMID- 9642304
TI  - Induction of c-fos/c-myc expression by epidermal growth factor decreases with
      alteration of their gene binding proteins in senescent fibroblasts.
AB  - OBJECTIVE: To observe the changes of proto-oncogene c-fos/c-myc expression and
      its relation to specific transcription factors in human senescent fibroblast
      after epidermal growth factor (EGF) addition. METHODS: The c-fos/c-myc expression
      were analysed by Northern blot. Transcription factors were analysed by
      Southwestern blot. RESULTS: (1) The expression of c-fos/c-myc was less
      susceptible to induction by EGF as the cells aged. (2) EGF increased the binding
      of protein P91 to c-fos with regulatory sequence and P80 to c-myc with regulatory
      sequence, but the increased levels of both proteins were significantly reduced in
      senescent cells. CONCLUSIONS: Inability of c-fos/c-myc gene induction by EGF in
      senescent cells might be correlated with some DNA-binding proteins.

PMID- 9642305
TI  - A study on rIL-4 and IFN-gamma regulating IgE synthesis in bronchial asthma
      patients.
AB  - OBJECTIVE: To investigate the cytokines responsible for pathophysiology of
      asthma. METHODS: In vitro effects of recombinant interleukin-4 (rIL-4) and
      interferon-gamma (IFN-gamma) on synthesis of immunoglobulin E (IgE) by peripheral
      blood mononuclear cells (PBMC) were studied in 30 asthmatic patients and 25
      normal controls. RESULTS: Spontaneous IgE synthesis by PBMC significantly
      increased in patients with asthma compared with the controls (t = 4.471, P <
      0.001). Although the maximum amounts of IgE synthesis using PBMC after
      stimulation with rIL-4 were almost the same in the patients with asthma and in
      the controls (P > 0.05), the enhancement rate of rIL-4-induced IgE synthesis was
      lower in the asthma patients than in the controls (t = 4.6719, P > 0.005). IFN
      gamma suppressed both spontaneous and rIL-4-induced IgE synthesis by PBMC in the
      asthma patients. The suppressive effect on IgE synthesis was more prominent in
      the patients with asthma than in the controls (t = 7.1833, P < 0.001).
      CONCLUSIONS: Asthma attacks are related to IgE-dependent trigger mechanism. The
      imbalance of IL-4 and IFN-gamma in vivo is the cause of elevated IgE than can
      produce mediators release and asthma attacks. IFN-gamma can inhibit IgE
      synthesis, so IFN-gamma may be a new approach to the treatment of asthma.

PMID- 9642306
TI  - Primary structure and variability of partial nonstructural gene 5 region of
      hepatitis G virus.
AB  - OBJECTIVE: To sequence partial nonstructural 5 (NS5) gene of hepatitis G virus
      (HGV) in the sera of Chinese patients with chronic non-A-E hepatitis or hepatitis
      B virus (HBV) infection. METHODS: Total nucleic acid was extracted from the sera
      of 35 patients with chronic non-A-E hepatitis and 20 patients with HBV infection,
      then it was subjected to reverse transcriptase-nested-polymerase chain reaction
      (RT-nested-PCR) with primers derived from the putative nonstructural gene 5 (NS5)
      region of HGV. The positive PCR products (994 bp in length) were directly
      sequenced using the Sang's method after purification. RESULTS: HGV RNA was
      detected in 1 of the 35 patients (2.9%) with chronic non-A-E hepatitis and 5 of
      the 20 patients (25%) with HBV infection. All the 6 positive samples were
      sequenced. These 6 Chinese isolates exhibited 87.21% to 93.92% nucleotide
      sequence identities with 3 reported isolates (GBV-C, PNF2161, R10292) over the
      994 nucleotides examined, while the nucleotide homologies among the 6 isolates
      were 90.09% to 93.82%. And 93.61% to 98.72% homologies were found at the deduced
      amino acid level in comparing the 6 isolates with 3 reported ones, while 93.61%
      to 98.40% amino acid identities were found among the 6 isolates. In the region
      sequenced, there existed 16 conserved proline residues and 8 conserved cysteine
      residues. CONCLUSIONS: Six isolates of HGV were obtained from different Chinese
      patients in this study. The partial nucleotide sequences, as well as amino acid
      sequences, of the putative NS5 region of HGV in Chinese patients are relatively
      conserved. The overall degree of nucleotide conservation (90.09% to 93.82%) among
      Chinese isolates may make this region of the genome suitable for the development
      of diagnosis reagents.

PMID- 9642307
TI  - Autoantibodies and anti-interferon antibody in patients with chronic viral
      hepatitis and its clinical significance: a preliminary investigation.
AB  - OBJECTIVE: To determine the antoantibodies and anti-interferon antibody in
      chronic viral hepatitis patients treated with interferon and the relation of the
      antibodies to the curative effect of interferon. METHODS: Forty chronic viral
      hepatitis patients (twenty cases for hepatitis B; twenty patients for hepatitis
      C) were studied. Indirect immunofluorescence assay (IFA) was used to measure the
      autoantibodies. Enzyme immunoassay (EIA) was used to measure the anti-interferon
      total antibody. RESULTS: Compared with normal groups, the autoantibodies in
      patients increased significantly (P < 0.01), and the anti-interferon antibody in
      chronic hepatitis B and hepatitis C patients had an obvious difference (P <
      0.05). As for the curative effect, the presence or absence of autoantibodies did
      not have a distinct significance in patients treated with alpha-interferon, but
      the patients with anti-interferon antibody before or after therapy might have a
      different response to alpha-interferon. CONCLUSIONS: It was suggested that the
      presence of autoantibodies was not a contraindication to the use of interferon in
      patients with chronic viral hepatitis; the clinical significance of anti
      interferon antibody should be further studied.

PMID- 9642308
TI  - Bridging nerve defects with differently treated muscle grafts: assessment of
      microsphere technique for measurement of blood flow in rats.
AB  - OBJECTIVE: To select advanced points from differently treated muscle grafts and
      explore a new conduit to bridge nerve defects. METHODS: A total of 70 Sprague
      Dawley rats were employed in this experiment. We applied a frozen probe to freeze
      the muscle in situ to disrupt any cellular elements of the local muscle grafts,
      but blood vessels to the muscle were carefully preserved. Radioactive microsphere
      technique was employed to visualize the blood supply to the muscle grafts.
      Immunohistochemical staining and ultrastructural observation were also carried
      out to assess the results of nerve regeneration. RESULTS: The in-situ frozen
      muscle grafts were revascularized within the first 3 days, which led to fast
      migration of macrophages and Schwann cells. That was really reflected in the
      final results: the early incursion of regenerating axons, more regenerating axons
      at the early stage both in the grafts and distal stumps, and thicker myelin
      sheath of regenerating axons. CONCLUSIONS: The in-situ frozen autogenous muscle
      graft is useful in the repair of sciatic nerve of rats. In the thicker and longer
      grafts the benefits will be more remarkable. It will be the most useful technique
      for nerve repair, especially in the repair of a large nerve gap in a poor
      recipient bed.

PMID- 9642309
TI  - A new method for computerized tomography diagnosis of early transtentorial
      hernia.
AB  - OBJECTIVE: To evaluate a new scanning method designed for the diagnosis of early
      transtentorial hernia as compared with the routine scanning method (parallel to
      orbitomeatal line). METHODS: 102 patients with unilateral high intracranial
      pressure and 100 volunteers without any cranial symptoms and signs were scanned
      on (1) the plane perpendicular to the plane of clivus and (2) the plane parallel
      to orbitomeatal line, a line joining the apex of the dorsum sellae and the lowest
      point of the clivus. RESULTS: Vertical-to-clivus scanning method directly
      demonstrated the temporal transtentorial hernia in 48 of 102 patients with
      unilateral high intracranial pressure, but the orbitomeatal line scanning method
      was not able to show this direct finding. The projected tissue of the temporal
      lobe could be obviously shown and the degree of the hernia could be judged
      directly on the CT imaging with the vertical-to-clivus scanning method.
      Therefore, the CT diagnosis criterion of the hernia was suggested as follows: the
      hernia would be determined if the downward shift of the temporal lobe was more
      than 3 mm and suspected if less than 3 mm with ipsilateral high intracranial
      pressure. CONCLUSION: This new method presented a superiority in showing the
      temporal transtentorial hernia for the patients with a cranial emergency.

PMID- 9642310
TI  - Effects of prostaglandin E2 and all-trans retinoic acid combination on induced
      differentiation of human acute promyelocytic leukemia NB4 cells.
AB  - OBJECTIVE: A human promyelocytic leukemia (APL) cell line NB4 was used to
      demonstrate the synergistic effects between all-trans retinoic acid (ATRA) and
      prostaglandin E2 (PGE2) on growth inhibition and cytodifferentiation induction.
      METHODS: NB4 cells were cultured in the presence of either ATRA or PGE2 as a
      single agent or in combinations at various ratio. Cell growth was measured and
      myeloid differentiation was tested on consecutive days over the whole course of
      culture. RESULTS: PGE2 and ATRA synergistically induced the myeloid
      differentiation of NB4 cells. In comparison with ATRA alone, the combination of
      PGE2 with ATRA caused an almost 20-fold decrease of effective concentration of
      ATRA. CONCLUSION: The combination of ATRA and PGE2 at an appropriate ratio may
      provide a convenient oral regimen of combined differentiation therapy for a
      better clinical outcome in APL patients.

PMID- 9642311
TI  - Clinical features of 201 cases with Duane's retraction syndrome.
AB  - OBJECTIVE: To summarize the clinical features of 201 cases with Duane's
      retraction syndrome (DRS) and discuss its differential diagnosis. METHODS: We
      retrospectively summarized the 201 cases from 1979 to 1996. The clinical features
      including chief complaints, sexual distribution, age at first visit, laterality,
      type of presentation, ocular deviation in the primary position, refractive
      errors, amblyopia, globe retraction, change of the palpebral fissure, upshoot and
      downshoot in adduction, binocular single vision, and its associated ocular and
      non-ocular anomalies were analysed. RESULTS: There were 99 males and 102 females
      with a female-to-male ratio 1:1. The 65.88% of DRS cases had left eye involvement
      with two-to-one predilection for the left eye. The most common form of the
      syndrome was type I (184 patients, 91.54%). Exotropia was the most common
      deviation in the primary gaze (72 patients, 35.8%). Among 118 patients, most had
      abduction deficits, globe retraction in adduction, and faceturn as to maintaining
      single binocular vision. Crocodial tears (26 patients, 11.93%) was the most
      frequently encounted ocular abnormalities. CONCLUSIONS: Diagnosis of DRS in a
      typical case is not difficult, however, children with bilateral abduction
      deficits which may mimic DRS must be differentiated from the following four
      motility disorders, namely, abducens nerve palsy, Moebius syndrome, congenital
      oculomotor apraxia, and congenital or infantile esotropia.

PMID- 9642312
TI  - A survey of antipsychotic treatment for schizophrenia in Hong Kong.
AB  - OBJECTIVE: To obtain information on prescription pattern of antipsychotic drugs
      for schizophrenic in-patients treated in public hospitals in Hong Kong. Four main
      areas of antipsychotic treatment are reported in this paper: (1) doses of
      antipsychotic drugs, (2) the practice of giving multiple antipsychotic agents
      simultaneously, (3) use of antipsychotics in divided daily doses and (4) co
      administration of antipsychotic and antiparkinson drugs. METHODS: A cross
      sectional survey of prescriptions of antipsychotic medication for a
      representative sample of 957 schizophrenic in-patients was conducted on a
      randomly chosen census day. Questionnaire items included basic demographic and
      clinical data, as well as inventory for all medications received by patients on
      census day. RESULTS: The mean antipsychotic dose was 854 +/- 759 (median: 600;
      range) 0-4450) mg CPZeq. Over two-third of the patients were given more than drug
      concurrently while less than 20% received the medication in multiple divided
      doses. Antiparkinson drugs were prescribed with antipsychotic medication in
      69.61%, of the subjects. There were few differences between acute and chronic
      patients with respect to their respective prescription patterns. CONCLUSIONS:
      Antipsychotic treatment of schizophrenic inpatients in Hong Kong is largely in
      accord with international standards. Problematic areas identified for closer
      scrutiny include the concurrent use of more than one antipsychotic drug for both
      acute and chronic patients, and the higher than recommended doses for
      antipsychotic drugs and frequent use of antiparkinson medication for chronic
      patients. Dissemination of these results, accompanied by continuing medical
      education about psychopharmacology, are planned to further improve the quality of
      treatment for schizophrenic patients.

PMID- 9642313
TI  - Changes of ultrasonography and two serum biochemical indices for hepatic fibrosis
      in schistosomiasis japonica patients one year after praziquantel treatment.
AB  - OBJECTIVE: To observe the changes of abdominal sonography and 2 biochemical
      indicators for hepatic fibrosis before and after treatment with praziquantel in
      schistosomiasis japonica patients. METHODS: Fifty-five persons infected with
      Schistosoma japonicum and treated with praziquantel were examined with
      ultrasonography and serum hyaluronic acid (HA) and type III procollagen (PC III)
      before and 1 year after treatment, and their data were compared with those in 55
      normal controls. RESULTS: With comparison of the data before praziquantel
      treatment, the length of the left liver lobe and the spleen in 55 patients all
      decreased (P < 0.01) 1 year after treatment. No significant change was seen in
      interior diameter (d) of the portal vein, while a decrease in the ratio of the
      exterior diameter (D) and interior diameter of the second branch of the portal
      vein was very significant (P < 0.01). Compared with the data in normal control,
      significantly higher levels in the thickness of the left lobe, the maximum
      oblique diameter of the right lobe, the length of the spleen, spleen index, the
      interior diameter of the portal vein and D/d ratio were seen in the patients both
      before and after treatment. The abnormal rate of the 2 serum parameters for
      hepatic fibrosis decreased significantly after treatment. CONCLUSIONS: Parameters
      of hepatic fibrosis either by ultrasonography or by the 2 biochemical tests
      showed a significant improvement in 55 patients 1 year after treatment, although
      some of the indices did not yet return to normal levels.

PMID- 9642314
TI  - Observation of developing cercaria of Schistosoma japonicum on ultrastructural
      level and remarks at its morphology of mature stage.
AB  - OBJECTIVE: To study the developing cercaria of Schistosoma Japonicum (S.
      japonicum) on ultrastructural level by transmission electron microscope (TEM) for
      analyzing the morphological dynamic changes of the tegument, glands and
      musculature. METHODS: Artificial infected Oncomelania hupensis were dissected
      under dissecting microscope and the daughter sporocysts picked up for studying
      the germinal cells stage (S1). The other embryonic cercaria were selected
      according to the modified parameter of Chen and Bier (1972). The specimens were
      prepared by conventional procedure of the laboratory of TEM and were observed by
      Hitachi H600. RESULTS: Beside the germinal cell stage (S1), this is the first
      chronological study on the morphological development of S. japonicum cercaria
      from S2-S5 concerning the tegument and its elements (glycocalyx, sensory papilla,
      basal lamina and spine), head and acetabular gland and musculature of the body
      and tail. This article discusses the ultrastructural morphological differences
      from prior authors and emphasizes on the postacetalar gland and the pattern of
      tail musculature of the matured stage cercaria. CONCLUSIONS: According to the
      cell division and differentiation, the process of development may be divided into
      5 stages: S1, the single germinal cell stage; S2, the germinal ball stages: major
      multiplication and minor differentiation; S3, tail budding embryonic stage, both
      active in multiplying and differentiating; S4, the pre-matured stage, major
      differentiation and minor multiplication; and S5, the fully matured stage
      (completing the differentiation).

PMID- 9642315
TI  - Studies on the transmission potential of filariasis in controlled areas of Henan
      Province.
AB  - OBJECTIVE: To study the regular pattern of growth and declination or the
      transmission potential of filariasis after the disease was basically (the
      microfilarial rate was lower than 1%) in Henan Province in 1987. METHODS:
      According to the distribution of filaria species and original microfilarial rate,
      in 7 surveillance sites in 7 counties (cities) the etiology and mosquito vector
      surveys were carried out continuously during 1988-1995 and no control measurement
      for pathogen was taken. RESULTS: Ten residual microfilaremias became negative
      gradually in the first 6 years and no new microfilaremias occurred during 1988
      1995. During 1993 to 1995, the microfilaremias rate of population in the sites
      was 0. The natural infection rates of filarial larvae in vector mosquito were
      0.1%-0. During the 8 years, 15 vector mosquitos were positive with a total of 18
      filarial larvae which were all of first or second-stage larvae. The C. pipiens
      pallens was the main vector, the second was A. sinensis, with a small number of
      C. fatigans and A. anthropophagus. The man-biting rates of mosquitoes for outdoor
      sleepers fluctuated greatly, the highest one was 360.6 mosquitoes/person per
      night and the lowest, 7.2. The man-biting rates of mosquitoes for sleepers inside
      mosquito-net was about 1 mosquito/person per night. The proportion of multiparous
      mosquitoes also fluctuated more greatly, the highest one was 88.1% and the lowest
      27. 2% According to the data described above, the man-biting rate of vector
      mosquito which contained filarial L3 was 0. CONCLUSIONS: The results suggested
      that after the microfilarial rate was lower than 1%, the residual microfilaremias
      became negative gradually in 3-6 years, and the transmission of the disease was
      blocked. Therefore, in the areas where filariasis was basically controlled,
      elimination of the disease was attainable within sight.

PMID- 9642316
TI  - Study on stress distribution of the condyle.
AB  - OBJECTIVE: To investigate the internal state of stress distribution in healthy
      human condyles and to offer some references for application of the
      temporomandibular joint (TMJ) biomechanics. METHODS: Six male volunteers were
      selected to perform CT examination of the TMJ with 1.5 mm-thick sections at 1.5
      mm intervals. Three dimensional image reconstruction of the joint was performed
      in the SUN workstation and the CT data were converted into the decimal system.
      The three dimensional finite element model mesh generation resulted from 1188
      elements and 264 nodes in each condyle. Stress calculation was performed with SAP
      V program, and the results were converted into mechanical density scalar. During
      the study, the internal state of stress distribution on each side condyle in
      every subject was analysed on the basis of loading on the anterior articular
      surface of the condyle. RESULTS: Stress was concentrated in the anterior
      articular surface of the condyle and was highest at the loading point. The
      condylar cortical bone was the main load-bearing area. The level of stress
      distribution in the cancellous bone of the condyle was very low. Near condylar
      neck stress was well-distributed on the cortical. The internal state of stress
      was essentially symmetrical on the same cuts of both side condyles. CONCLUSIONS:
      The results showed that three dimensional finite element analysis may indicate
      the internal state of stress distribution in the condyle, suggesting that a
      combination of the three dimensional finite element methods and the three
      dimensional imaging technique may be a useful means for diagnosis and treatment
      of TMJ diseases.

PMID- 9642317
TI  - Eosinophilic granuloma of the cervical spine.

PMID- 9642318
TI  - Retinal capillary pericyte apoptosis in early human diabetic retinopathy.
AB  - OBJECTIVE: To investigate the nature of retinal capillary pericyte dropout in
      early human diabetic retinopathy. METHODS: In the present study, neural retinas
      of 12 postmortem eyes from 6 patients (3 diabetic and 3 nondiabetic) were first
      fixed in buffered formaldehyde and then digested with trypsin. The preparations
      of trypsin-digested retinal blood vessels were stained with terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) technique
      and then with perdiodic acid-Schiff technique (PAS), and counter-stained with
      hematoxylin to evaluate DNA fragmentation of cell nuclei and diabetic changes of
      retinal capillaries. RESULTS: TUNEL-positive apoptotic pericytes were observed in
      retinal capillaries in all three diabetic patients in this study. The TUNEL
      positive pericytes were presented as darker stained cells with PAS-hematoxylin
      staining. A few TUNEL-positive retinal capillary endothelial cells were
      discovered in both eyes of one of the three diabetic patients. Neither TUNEL
      positive pericytes nor positive endothelial cells were found in the three
      nondiabetic patients. A variety of typical diabetic microvascular changes were
      noticeable with PAS-hematoxylin staining in trypsin-digested retinal preparations
      from diabetic patients. These changes included thickened capillary walls,
      microaneurysms, "ghost-cell"-appearance of pericytes, acellular segments of
      capillaries, and a decreased ratio of retinal capillary pericytes to endothelial
      cells. All of these changes are characteristics of diabetic retinal
      microangiopathy. CONCLUSIONS: Retinal capillary pericyte apoptosis is a specific
      form of cell death which occurs during the early development of diabetic
      retinopathy. The significant decrease in the ratio of pericytes to endothelial
      cells and the predominant TUNEL-positive pericytes over endothelial cells suggest
      that a greater impact of apoptosis-related mechanisms occurs in pericytes than in
      endothelial cells and, thereby, a greater loss of pericytes takes place in early
      diabetic retinopathy. Apoptosis, therefore, is an important mechanism of pericyte
      dropout in the early diabetic retinopathy.

PMID- 9642319
TI  - Color Doppler imaging diagnosis of intra-ocular tumor.
AB  - OBJECTIVE: To demonstrate the color Doppler imaging (CDI) of intra-ocular tumors
      and its importance in the diagnosis of these tumors. METHODS: Ninety-two patients
      with intra-ocular tumors (105 eyes) were examined by using CDI to observe the
      vasculature of these tumors, and using SAS soft ware to analyze the results.
      RESULTS: Blood flow signal was found in retinoblastoma, melanoma of choroid,
      angioma of choroid, angioma of optic disc, Coats' disease, persistent
      hyperplastic primary vitreous (PHPV) and metastatic tumors of choroid, but not
      found in choroid osteoma and melanocytoma of optic disc. The blood flow decreases
      in central retinal artery in choroidal melanoma and also in ophthalmic artery,
      central retinal artery and posterior ciliary artery in angioma of choroid (P <
      0.01). It was found that blood velocity is much faster in choroidal melanoma than
      in choroidal angioma (P < 0.05). CONCLUSIONS: CDI is very important and helpful
      in the diagnosis of intra-ocular tumors.

PMID- 9642320
TI  - Correlation between retinal fluorescein angiography and blood viscosity and other
      factors in patients with primary open angle glaucoma.
AB  - OBJECTIVE: To investigate the correlation among retinal fluorescein angiography,
      blood viscosity, and other factors in patients with open angle glaucoma (POAG).
      METHODS: Multiple step regression analysis was made to investigate the
      correlation between each of the following blood vessel filling times: the arm
      choroid (A-CT), arm-retinal artery (A-AT), and retinal artery-venous (A-VT) of
      the fundus fluorescein angiography (FFA) in 122 eyes with POAG and each of the
      following related factors in hemorrheology: whole blood apparent viscosity at
      low, medium and high shear rates, plasma viscosity and hematocrit. Also, the same
      analysis was applied to investigate the correlation between each of the A-AT, A
      VT of the FFA in 70 eyes with POAG and the following factors: systolic blood
      pressure, diastolic blood pressure, age and whole blood apparent viscosity at low
      shear rate. RESULTS: The whole blood apparent viscosity at low shear rate was
      closely related to A-CT and A-AT, while hematocrit was closely related to A-VT of
      the FFA. The whole blood apparent viscosity at low shear rate and age, especially
      the whole blood apparent viscosity, was closely related to A-AT, A-VT of the FFA.
      CONCLUSION: Blood viscosity can affect the filling times of the FFA in POAG.

PMID- 9642321
TI  - A corneal topographic analysis of astigmatism after excimer laser photorefractive
      keratectomy.
AB  - OBJECTIVE: To identify the astigmatism changes after excimer laser
      photorefractive keratectomy (PRK) and the visual influence of astigmatism.
      METHODS: 109 myopic eyes followed up for more than 1 year were analyzed by
      videokeratography, and their visual acuities were examined. Before the operation,
      the astigmatic errors with cycloplegic refractive examination were -1.00
      approximately -2.00 D. RESULTS: The position of astigmatism axis was basically
      consistent with that in corneal topography, but in astigmatism diopter there were
      some differences between the cycloplegic examination and topographic analysis. A
      stigmatism was found in 62% of the eyes, asymmetrical in 33% and against-the-rule
      in 5% by using topographic analysis. There was little change observed in the
      position of astigmatism axis after PRK observed. Some changes of postoperative
      astigmatism diopter were seen in different periods. It increased in the
      postoperative 10 days or 1 month, and afterwards gradually decreased and became
      stable in 6 months to 1 year. The postoperative residual astigmatism was low in
      degree, and did not affect the visual acuity. The actually corrected diopter was
      within the anticipated corrected diopter range of +/- 1.00 D. accounting for
      97.4%. CONCLUSION: By using spherical equivalent method of calculation in PRK,
      the refractive correction of the operation cases with myopia and low degree of
      astigmatism (< -2.00 D) was satisfactory.

PMID- 9642322
TI  - Stent thrombosis with different types of intracoronary stents: is it still a
      problem?
AB  - OBJECTIVE: The reported results of intracoronary stenting with Palmaz-Schatz
      stents using the low dose anticoagulation protocol have been encouraging and no
      stent thrombosis was observed. The effectiveness of such method extending to the
      use of other types of stents was therefore evaluated in this study. METHODS: All
      patients followed the anticoagulation protocol (heparin and warfarin) using non
      heparin-coated stents. From September 1995, 92 patients received intracoronary
      stenting (69 men, 23 women, mean age 60.9 years). Altogether 117 stents were
      implanted in 99 target arteries and 106 lesions. RESULTS: A total of 50.4% of the
      stents were bare stents (stents without protective sheaths). Both coil stents and
      slotted tubular stents were used. Stenting was performed without the guidance of
      intravascular ultrasonography and high-pressure poststenting inflation was used
      in only 24.0% of patients with less than optimal angiographic results. The mean
      (+/- SD) coronary minimum luminal diameter changed from 0.63 +/- 0.39 mm to 3.12
      +/- 0.48 mm immediately after stenting. Both stent thrombosis rate and femoral
      bleeding complication rate remained at 0%. Four bare stents could not be deployed
      in the first instance but without sequels. No morbidity nor mortality was
      recorded. The mean hospital stay remained at a mean of 4.5 days. All patients
      (100%) were followed up regularly. The mean (+/- SD) clinical follow-up period
      was 229 +/- 173 days. Clinical symptoms improved in all patients. CONCLUSIONS:
      These findings further support that the method is safe and stent thrombosis was
      not observed. Post-stenting recoil was more with coil stents. Dislodgment and
      potential risk of embolization could not be underestimated with bare stents. The
      restenosis rate between different types of stents remains to be determined.

PMID- 9642323
TI  - Some changes of receptor and postreceptor signal transduction regulated by
      somatostatin in pituitary hGH-secreting adenomas.
AB  - OBJECTIVE: To investigate the disturbance in the function of SRIF receptor, Gi
      protein and Ca2+ channel in hGH adenoma cells and to evaluate their significance
      in the pathogenesis of pituitary hGH adenomas. METHODS: All 25 patients with
      pituitary hGH adenoma who were involved in this study had typical acromegalic
      manifestation and high fasting serum hGH levels of > 5.0 micrograms/L which were
      not suppressed to < 3.0 micrograms/L by oral glucose tolerance test. The
      pituitary hGH adenoma tissue obtained from transphenoidal operation was digested
      by collagenase and the dispersed adenoma cells were cultured in the monolayer.
      The effects of octreotide (SMS), a long-acting agonist of somatostatin, on hGH
      secretion and intracellular cAMP level were observed and the influences of
      pertussis toxin (PT), an inhibitor of Gi protein, and Ca2+ ionophore A23187 or
      KCl on the inhibitory action of octreotide on hGH secretion were also
      investigated in the cultured pituitary hGH adenoma cells. RESULTS: A total of
      16.0% (4/25) of cultured pituitary hGH adenomas did not respond to octreotide
      (100 nmol). The inhibitory effect of octreotide on hGH secretion was not blocked
      by PT (50 ng/ml) and A23187 (10 mumol) or KCl (22.5 nmol) in 31.6% (6/19) and 35%
      (7/20) of hGH adenomas, respectively. The effects of octreotide on hGH secretion
      and intracellular cAMP levels were studied in 10 cultured hGH adenomas.
      Octreotide suppressed both hGH secretion and cAMP levels in 5 cases; inhibited
      only hGH secretion or the cAMP level in 3 cases and 1 case respectively; and
      affected neither hGH secretion nor cAMP level in the last case. CONCLUSION: There
      were abnormalities in the SRIF receptor and/or postreceptor signal transduction
      in 16.0% of hGH adenomas which did not respond to octreotide. The defects in Gi
      and/or Ca2+ channels were found in 52.4% (11/21) of hGH adenomas which had
      responded to octreotide. These defects might induce diminution of the inhibitory
      action of SRIF on hGH secretion and might be the causes of hypersecretion in some
      pituitary hGH adenomas.

PMID- 9642324
TI  - Analysis of tumor specific immunoglobulin gene rearrangement in peripheral blood
      B-cells of multiple myeloma patients by a PCR-SSCP method.
AB  - OBJECTIVE: To analyze the clonal relationship between lymphocytes in peripheral
      blood (PB) and myeloma cell in bone marrow (BM) for proving the existence of
      circulating tumor cells in multiple myeloma (MM) patients. METHODS: Eighteen
      patients with MM who have no cytomorphologic plasma cells and CyIg+ cells in PB
      demonstrated by anti-kappa and anti delta MoAbs using ABC method were involved in
      the present study, including 3 cases in phases I-II and 15 cases in phase III.
      The complementary determining region 3 (CDR3) of immunoglobulin heavy chain (IgH)
      gene was amplified by polymerase chain reaction (PCR). We further analysed the
      single strand conformation of the PCR products by single strand conformation
      polymorphism (SSCP) analysis to detect the mononuclear cells in PB and BM of the
      patients simultaneously. RESULTS: The same PCR products of IgH-CDR3 gene with BM
      samples were found in PB of 11 MM patients. The same PCR products and single
      strand conformation in both PB and BM were found in 9 cases. CONCLUSIONS: This
      study has proved the presence of identical clonal malignant cells in PB and BM of
      MM patients. B cells are involved in the pathogenesis of MM.

PMID- 9642325
TI  - Effects of cyclosporine A on serum and urinary soluble interleukin-2 receptor in
      patients with lupus nephritis.
AB  - OBJECTIVE: To evaluate the association of the level of urine and serum soluble
      interleukin-2 receptor (sIL-2R) with disease activity and response to
      cyclosporine A (CsA) therapy in patients with lupus nephritis (LN). METHODS:
      Sixteen hospitalized patients with LN were studied. At admission, fifteen
      patients had type IV-LN and one had type V-LN. All patients received CsA 6 mg/kg
      per day for 6-8 weeks, then tapered off gradually to 2 mg/kg per day. The levels
      of urinary and serum sIL-2R were determined by enzyme-linked immunosorbent assay
      (ELISA). Serum antinuclear antibody (ANA), anti-dsDNA antibody (A-ds-DNA),
      complement C3 and C4, total IgG, creatinine, urinary red blood cells and protein
      excretion, and lymphocyte subpopulations in the peripheral blood were also
      measured before and after CsA treatment. RESULTS: In LN patients, both urinary
      (534 +/- 101 U/ml) and serum SIL-2R levels (326 +/- 148 U/ml) were higher than
      those in normal controls. These findings were associated with higher levels of
      peripheral blood CD4 + and CD8 + lymphocytes (29.3 +/- 4.24 and 28.6 +/- 9.12%),
      higher titer of serum anti-ds-DNA, lower levels of serum complement C2 and C4
      (0.98 +/- 0.23 and 0.24 +/- 0.12 g/L), as well as more proteinuria (Upro 2.99 +/-
      0.76 g/24 hrs) and hematuria (URBC 83.9 +/- 95.2 10(4)/ml). These abnormalities
      were gradually ameliorated by CSA therapy. The changes in the levels of both
      serum (116 +/- 58.6 U/ml) and urine (136 +/- 43.2 U/ml) SIL-2R induced by CsA (at
      8 weeks) were correlated with the changes in the levels of CD4 + and CD8 + cells
      (23.2 +/- 3.30 and 26.7 +/- 3.54%), degrees of immune abnormalities (serum C3 and
      C4 1.28 +/- 0.14 and 0.42 +/- 0.06 g/L), and renal injuries (Upro 1.07 +/- 0.46
      g/24 hrs, URBC 5.82 +/- 3.15 10(4)/ml). CONCLUSIONS: These results suggest that
      serum and urinary sIL-2R are sensitive markers for the disease activity in
      patients with LN. CsA, a powerful immunosuppressive agent, significantly improves
      both immunologic disorders and renal functional impairments, the mechanism of
      which on patients with LN appears to inhibit the lymphocyte activation in the
      peripheral blood and renal tissues as indicated by the decrease in sIL-2R levels.

PMID- 9642326
TI  - Guillain-Barre syndrome: clinical analysis and pathological study on sural nerve
      biopsy of forty cases.
AB  - OBJECTIVE: To make clinical analysis and pathological study on 40-case Gullain
      Barre syndrome with sural nerve biopsy. METHODS: A total of 90 cases of GBS were
      retrospectively analyzed of which sural nerve biopsies were performed in 40
      cases. The type of GBS was determined according to Asbury and Ropper criteria,
      and its correlation with pathological findings was studied. RESULTS: In the 40
      biopsy cases, demyelination was the predominant pathological change in 38 cases.
      Mild axonal degeneration was also seen in 13 of the 38 cases. Prominent axonal
      degeneration was seen in only 2 of 13 cases. The increased monocyte infiltration
      and varied capillary permeability were observed in 19 of 25 cases. Onion-bulb
      like changes were seen in 6 cases. CONCLUSION: We studied the correlation between
      paresthesia and the pathological findings of sural nerve biopsy and concluded
      that sural nerve biopsy is very useful in the diagnosis of GBS and its variant.

PMID- 9642327
TI  - Clinical curative effects of dimercaptosuccinic acid on hepatolenticular
      degeneration and the impact of DMSA on biliary trace elements.
AB  - OBJECTIVE: To observe the biliary copper content of nonhepatolenticular
      degeneration (HLD) controls and changes in the trace elements in the bile,
      cerebrospinal fluid, blood and urine of hepatolenticular degeneration patients
      before and after dimercaptosuccinic acid (DMSA) treatment in order to further
      explore the etiological mechanism of HLD and prove the therapeutic effect of DMSA
      on HLD patients. METHODS: A consecutive series of 20 patients with HLD were given
      DMSA orally for 4 weeks. Adult dosage was 1.5 g/day and child dosage 1.0 g/day.
      Their bile, cerebrospinal fluid, blood and urine samples were obtained before and
      after treatment with DMSA through duodenal drainage and lumbar puncture. Biliary
      samples of 22 non-HLD controls were taken by drainage tube after surgical
      operation. Hitachi-208 atom absorption spectrophotometer was used to assay the
      content of copper, zinc and iron of each sample. RESULTS: DMSA could effectively
      improve the symptoms such as dysphasia, salivation, dysphagia and darkening of
      the skin; limb trembling and myotonia came second; but it showed no obvious
      effect on dysstasia, limb contracture and deformity, and hepatosplenomegaly. It
      was effective for the patients who were younger and had no obvious hepatic
      damage. No serious side effects were seen through the course of treatment.
      Laboratory study showed that biliary copper content of HLD patients was evidently
      lower than that of non-HLD controls (P < 0.01); DMSA could evidently improve
      biliary copper excretion besides clearly increase urinary copper excretion (P <
      0.01) and had nothing to do with biliary zinc excretion (P > 0.05). CONCLUSIONS:
      Biliary copper excretion disturbance participates directly in the pathophysiology
      of copper retention of HLD patients. DMSA is a favorable cupruretic drug for
      patients with HLD.

PMID- 9642328
TI  - Anti-acetylcholinesterase antibody in myasthenic syndrome.
AB  - OBJECTIVE: To examine the relationship between antibodies to acetylcholinesterase
      and myasthenic syndrome. METHODS: Serum class specific antibodies to
      acetylcholinesterase and acetylcholine receptor were prepared with solid phase
      enzyme-linked immunosorbent assay in 51 patients with myasthenic syndrome, 31
      controls with other neurological diseases (diseased controls) and 44 normal
      controls. RESULTS: The positive rate of anti-acetylcholinesterase antibody in
      patients with myasthenic syndrome was 25%, while the results of the other two
      control groups were negative. Furthermore, the positive rate in patients without
      myasthenia gravis was 45%, which was much higher than that (13%) in those with
      myasthenic gravis. CONCLUSION: Anti-acetylcholinesterase antibody may play a role
      in the pathogenesis of myasthenic syndrome.

PMID- 9642329
TI  - Diagnosis of intrathoracic masses by transesophageal color Doppler
      echocardiography.
AB  - OBJECTIVE: To evaluate the value of transesophageal color Doppler
      echocardiography in the diagnosis of intrathoracic masses. METHODS: Twenty
      patients with intrathoracic masses were examined by transesophageal
      echocardiography (TEE), including 12 patients with central lung masses and 8 with
      mediastinal masses. The neoplasms were explored by two-dimensional realtime
      ultrasonography, Doppler color flow imaging (DCFI) and pulsed Doppler (PD). The
      results were compared with computed tomography (CT), operative and pathological
      examination findings. RESULTS: We were able to identify the size, structure
      (solid or cystic), anatomic relationship, metastatic lymph nodes and venous
      carcinoembolus of the masses. Furthermore, the hemodynamic data in the
      vasculature inside the masses were detected. CONCLUSIONS: As a new method, TEE
      with Doppler technique is not only valuable in differentiating malignant and
      benign neoplasms but also useful for preoperative evaluation of the mass
      resectability in patients with intrathoracic neoplasms.

PMID- 9642330
TI  - Complications of laparoscopic cholecystectomy in China: an analysis of 39,238
      cases.
AB  - OBJECTIVE: To investigate the complications of laparoscopic cholecystectomy in
      China. METHODS: All Chinese articles about laparoscopic cholecystectomy published
      between April 1994 and November 1995 were identified through CMCC (Chinese
      Medical Computerized Contents). From more than 600 titles, 105 articles were
      screened for analysis. Another 21 articles from the 6th Biliary Surgical Congress
      and 300 cases from the General Hospital of PLA were added. A total of 39,238
      cases of laparoscopic cholecystectomy from 91 hospitals were studied. RESULTS:
      Severe complications of laparoscopic cholecystectomy were identified in 409
      (1.04%) patients, including bile duct injury (in 0.32% of patients),
      postoperative cystic duct leak (0.11%), postoperative bile leak (0.20%),
      peritoneal abscess (0.07%), bowel injury (0.06%) and postoperative hemorrhage
      (0.1%). Fourteen postoperative deaths (0.04%) resulted from operative injury.
      CONCLUSIONS: The data demonstrate that laparoscopic cholecystectomy is an
      operation associated with low morbidity and mortality rate, but bile duct injury
      is still a major problem. Complications of laparoscopic cholecystectomy can be
      minimized by improving operative procedure.

PMID- 9642331
TI  - Clinical study of desflurane on low flow anesthesia compared with sevoflurane and
      enflurane.
AB  - OBJECTIVE: To compare the hemodynamic change, course of recovery and adverse
      reaction in desflurane, sevoflurane and enflurane inhalation under low flow for
      patients undergoing selective abdominal surgery. METHODS: Following thiopental
      induction, 42 patients were divided into three groups: the first group received
      desflurane, the second sevoflurane and the third enflurane. During surgery, one
      of the agents around 1 minimum alveolar concentration (MAC) was used for
      maintenance, with fresh gas flow of 0.3-0.5 L/min for either desflurane or
      enflurane, and (0.8-1.0) L/min for sevoflurane. Heart rate (HR), blood pressure
      and end-tidal anesthetic concentration were monitored continuously. Time
      intervals from cutting off anesthetic to patient opening eyes, following
      commands, stating the time and location and recalling date of birth were all
      recorded. In addition, postoperative nausea or vomiting was traced. RESULTS:
      Desflurane caused the least cardiovascular depression. with mean arterial
      pressure (MAP) maintained significantly better at 10, 30 and 60 minutes of
      surgery and with HR stabilized right after incision as well. Its emergence was 2
      times faster than sevoflurane, and 5-6 times quicker than enflurane. However,
      nausea or vomiting was found the lowest in patients receiving sevoflurane, though
      no distinct difference was shown between desflurane and enflurane. Nevertheless,
      patients under desflurane suffered less. CONCLUSIONS: Desflurane offers
      significant advantages for clinical anesthesia maintenance over sevoflurane and
      enflurane. It provides minimal cardiovascular depression, much quicker recovery,
      yet still causes some nausea during emergence.

PMID- 9642332
TI  - Preliminary observation on the metabolism in spontaneous hereditary diabetic
      Chinese hamster (Shanyi colony).
AB  - OBJECTIVE: To observe the changes of tissue lithium content and its relationship
      with glucose metabolism in spontaneous hereditary diabetic Chinese hamsters
      (SHDCH). METHODS: Twenty diabetic and ten normal Chinese hamsters were paired and
      separated randomly into four groups: controls (C), diabetics (D), controls
      treated with lithium carbonate (CT) and diabetics treated with lithium carbonate
      (DT). The lithium carbonate treatment was administrated with drinking water
      containing lithium carbonate (0.2 mg/ml). Blood glucose levels were determined at
      0, 1, 3, 5, 6th month, and insulin levels at 1, 3, 6th month. The lithium
      contents in liver, kidney and muscles were determined at the end of 6th month,
      using wet digestion assay and ICP-AES. Concentrations of fructosamine, lactic
      acid, GPT, BUN were also evaluated. RESULTS: The data showed that in Group D the
      lithium levels in hepatic tissue were lower than in Group C (P < 0.05), and
      lithium contents in kidney and muscle also decreased. In Group DT, the lithium
      contents in tissues were higher than in Group D (P < 0.05) and similar to Group
      C. Blood glucose levels and fructosamine concentrations decreased while insulin
      and lactic acid levels did not alter significantly. GPT and BUN levels did not
      change in both Group CT and Group DT. CONCLUSIONS: There is lithium deficiency in
      hepatic, renal and muscular tissues from diabetic Chinese hamsters. Low-dose and
      six-month-treatments of lithium carbonate can improve tissue lithium deficiency
      and glucose metabolism, and do not damage liver and kidney functions.

PMID- 9642333
TI  - Effects of peroxovanadate complexes on reducing glycemia in diabetic rats and
      translocation of glucose transporter.
AB  - OBJECTIVE: To demonstrate the hypoglycemic effects and translocation of glucose
      transporter (Glut 1 and Glut 4) promoted by peroxovanadate and nicotinic acid
      complexes (nicotinic chelated bitriperoxovanadate, POR; N-O nicotinic chelated
      peroxovanadate, POV) in streptozotozin-induced diabetic rats. METHODS:
      Peroxovanadate complexes of nicotinic acid (POR and POV) were prepared and
      characterized in laboratory. POR, POV and vanadate were administrated in drink
      water. The muscles from diabetic rats were subjected to prepare plasma membrane
      and microsome membrane. Antibodies to COOH-terminal of glucose transporter were
      used in Western Blot to evaluate the translocation. RESULTS: POR and POV showed
      markedly hypoglycemic effects in streptozotocin (STZ)-induced diabetic rats. POV,
      which may be a N-oxide compound of peroxovanadate, have high potency of acute
      effects comparing to carboxylate-complexes of peroxovanadate (POR). In chronic
      tests, 1 mg/kg oral pathway POR could significantly reduce the plasma glucose
      levels over four week's treatment, whereas the same dose of single sodium
      vanadate or nicotinic acid did not have hypoglycemic effects. The net vanadium
      intake is about 1/90 of single effectively vanadate treatment. The Western Blot
      showed that POR increased the translocation of Glut 4 and Glut 1 from
      intracellular site of membrane. CONCLUSIONS: Peroxovanadate-nicotinic acid
      complexes (POR and POV) are the novel vanadyl that acutely and markedly reduce
      plasma glucose in a lower dose comparing to vanadate in STZ-DM rats by oral
      administration. Translocation of glucose transportor may take a part in their
      hypoglycemic effects.

PMID- 9642334
TI  - Collecting duct carcinoma of the kidney.
AB  - OBJECTIVE: To describe the clinical, pathologic and immunohistochemical
      characteristics of collecting duct carcinoma (CDC) of the kidney. METHODS: Five
      cases of CDC (3 males and 2 females, aged 41 to 67 years) were identified between
      January, 1990 and December, 1994. Routine histopathologic study and
      immunohistochemical examinations of the surgical specimens were performed.
      RESULTS: Four patients underwent radical nephrectomy; 3 have been alive without
      evidence of recurrence for 3 months, 2 years and 2.5 years, respectively after
      the operation. Bone metastasis was noted 2 months after the operation in 1 case.
      One patient was submitted to simple nephrectomy because of extensive regional
      node involvement and died of lung metastasis 14 months after the surgery.
      Grossly, the tumors were usually grey-whitish in color and located in the renal
      medulla. Microscopically, the characteristic structure of tubulo-papillary
      pattern could be identified. Marked desmoplastic reaction was noted and atypical
      hyperplastic changes were found in the adjacent collecting ducts.
      Immunohistochemical studies revealed positive results to epithelial membrane
      antigen, high molecular weight cytokeratin and peanut agglutinin. CONCLUSION: CDC
      of the kidney is a rare disease with a poor prognosis. Radical nephrectomy is
      recommended even if the tumor is small.

PMID- 9642335
TI  - Preliminary study of the effects of metoprolol and propafenone on ventricular
      arrhythmia with positive ventricular late potential.
AB  - OBJECTIVE: To compare the effects of metoprolol and propafenone in patients with
      ventricular arrhythmia (VA) of positive ventricular late potential (VLP) and to
      discuss the effect of medicine on high risk VA. METHODS: 30 A total of 128
      patients (78 males and 50 females) with VA of positive VLP were randomly divided
      into 3 groups. Groups A and B were given metoprolol and propafenone respectively,
      group C was given vitamin C as placebo. Twenty-four hours dynamic
      electrocardiogram and VLP were examined before treatment and 4 weeks after
      treatment. RESULTS: Propafenone could effectively control VA but could not
      reverse positive VLP to negative meanwhile it had proarrhythmia effect (2/40),
      metoprolol could effectively control VA (38/46) and reverse positive VLP to
      negative (39/46) with no obvious side effects. The dosage from 50 to 100 mg/day
      made no difference. VA and VLP had no significant changes in group C.
      CONCLUSIONS: Metoprolol is superior to other medicine for VA of positive VLP when
      the patients have no contraindication of preceptor blocking agents.

PMID- 9642336
TI  - Koshevnikov syndrome in a patient with MELAS plus syndrome: electron microscopic
      and neuroimage studies.

PMID- 9642337
TI  - Primary nasal ectopic pituitary adenoma: a case report.

PMID- 9642338
TI  - Aspergillosis of the larynx: a report of 8 cases.

PMID- 9642339
TI  - [Salvage surgery for cervical metastasis from nasopharyngeal carcinoma after
      radiotherapy].
AB  - One hundred and forty patients who had residual or recurrent lymph node
      metastasis from nasopharyngeal carcinoma after radiotherapy underwent salvage
      surgery. The overall 3 and 5 year survival rates were 50.1% and 27.3%, the 3 and
      5 year local control rates were 48.3% and 27.3%, the 3 and 5 years distant
      metastasis-free rates were 44.5% and 25.6% respectively. The most significant
      factors influencing survival and local control rates were the size and the
      involvement of the capsule of the lymph nodes. The size of the lymph node was the
      only influencing fastor for distant-metastasis-free survival. Distant metastasis
      was the most frequent factor of treatment failure (48.9%) followed by recurrence
      of neck mass (14.4%). The authors considered that the salvage surgery is an
      effective method in improving the survival rate. The reradiotherapy after surgery
      or/ and adjuvant chemotherapy is a new area for further investigation.

PMID- 9642340
TI  - [Study on expression of nm23-H1 gene in laryngeal cancer tissues].
AB  - The nm23 gene is a metastasis suppressor gene. There are now two known isotypes
      of human nm23, namely nm23-H1 and nm23-H2. Several investigators have reported
      that reduced expression of nm23-H1 is associated with metastasis or disease
      progression in some of the tumor cases. In this study, the expression of nm23-H1
      mRNA in the human laryngeal squamous cell carcinoma was investigated by Northern
      blot analysis. The levels of nm23-H1 mRNA were higher in cancers (n = 31) than in
      the adjacent normal tissues (n = 7), but the difference was not significant (P >
      0.05). There was a significant decrease of nm23-H1 mRNA levels in tumors with
      lymph node metastasis (n = 11) as compared with those without (n = 20) (P <
      0.01). Cancer tissues in clinical stages III-IV. (n = 23) also exhibited lower
      levels of nm23-H1 mRNA expression than those in stages I-II (n = 8) (P < 0.05).
      These results suggest that the nm23-H1 gene may play a role in the suppression of
      lymph node metastasis or disease progression in laryngeal cancer.

PMID- 9642342
TI  - [Speech restoration via a tracheo-esophageal tegmental valve fistula following
      total laryngectomy].
AB  - In order to restore the patients' speech function after total laryngectomy, the
      speech restoration operation has been done successfully in 12 patients with
      laryngocarcinomas by making tegmental valve fistula from esophageal flap and
      tracheal tissue after total laryngectomy. First, the trachea and the esophagus
      were separated, and a tissue flap 20mm in length from posttracheal wall was made.
      Its upper end was 10mm in width, lower end 8 mm, laterally 5 mm x 6 mm, the
      tracheal mucosa and cartilage were sewn up to from a tegmental valve, then, a
      tissue flap 20 mm in length from the preesophageal wall was done with its upper
      end 15 mm in width, lower end 10 mm. Then a tegmental valve fistula (speech-tube)
      was made by sewing up two flaps crisscross and a 12F catheter was inserted into
      the tegmental valve fistula as a supporter for 10 days. Finally, a tracheostomy
      was performed by sewing up the trachea to the neck skin. All patients could speak
      fluently and clearly after surgery and kept their sex and dialect characteristics
      whereas without misswallowing. The operation is a perfect way for total
      laryngectomy with speech restoration in patients with upper glottal or glottal
      laryngocarcinomas.

PMID- 9642341
TI  - [Prognosis of laryngeal carcinoma in youth].
AB  - The prognosis of 55 cases of laryngeal carcinoma in young people had been
      studied. The major factors mainly related to prognosis were smoking and
      misdiagnosis, while the tumour differentiation might be not so important. There
      was a high recurrence rate of 25.5% in the young patients and low 3- and 5-year
      survival rates of 47.4% and 34.5% respectively. The mortality of 1-year after
      surgery was 21.8%. The 3-and 5-year survival rates between total and partial
      laryngectomy made no difference. The survival rate of patients with positive node
      was lower. Early diagnosis is most important for young patients. Partial
      laryngectomy and neck dissection must be performed as far as possible.

PMID- 9642343
TI  - [Clinicopathological study on patterns of cervical lymph node metastases from
      squamous cell carcinomas (SCC) of the head and neck].
AB  - In order to investigate the patterns of cervical lymph node metastases from head
      and neck SCC, serial sections were performed on 384 radical neck dissection (RND)
      specimens. Positive lymph node was found in 60.4% RNDs. The cervical lymph node
      spread from SCC in the head and neck regions including oral cavity, oropharynx,
      hypopharynx and larynx has some predictable patterns, i.e., for primary SCC of
      the oral cavity, the majority of cervical lymph node metastases were clustered at
      levels I, II and III; and for primary carcinoma of the oropharynx, hypopharynx
      and larynx, a majority of node metastases were located at levels II, III and IV.
      The positive lymph nodes mainly distributed at only one level or consecutive
      levels. The rates of pathologically positive lymph node and extranodal spread
      grew with the increase of the clinical N-staging. It is suggested that
      supraomohyoid neck dissection (levels I, II and III) is particularly applicable
      to carcinomas of the oral cavity, and lateral neck dissction (levels II, III and
      IV) is applicable to carcinomas of the oropharynx, hypopharynx and larynx in
      patients with limited (N0 and N1) neck nodules, but for patients with N2 and N3
      nodules, RND is neccessary to eradicate the nodal metastases. Moreover, the
      postoperative radiotherapy is indispensable for ruling out the occult cervical
      lymph node metastaese in selective neck dissection.

PMID- 9642344
TI  - [Chemosensitivity test for head and neck cancers].
AB  - The chemosensitivities of 27 fresh specimens of head and neck cancers were tested
      with MTT assay to study the practicability and accuracy of the assay for the
      examination of chemosensitivity in head and neck cancer patients. The
      chemosensitivities among cancers of different primary sites, pathologic types,
      histological differentiations, DNA ploidies and estrogen receptors were compared
      in an attempt to evaluate the choice of anticancer drugs for individual
      chemotherapy. Eight anticancer drugs: Methotroxate (MTX), Mitomycin C (MMC),
      fluorouracil (5-Fu), Carboplatin (CBDCA), Pingyangmycin (PYM), Homoharringtonine
      (HHA), Etoposid (VP16) and Vincristine (VCR) were included. The success rate of
      MTT assay in the present study was 92.6% and the accuracy was relatively high.
      The sensitivity sequence was PYM > HHA > MTX > CBDCA > MMC > 5-Fu > VCR > VP16,
      which suggested HHA should be recommended first to the chemotherapy of head and
      neck cancer. No chemosensitivity differences were found among different primary
      sites histological differentiations and estrogen receptors. The chemosensitivity
      of squamous cell carcinoma was significantly higher than that of adenoid cystic
      carcinoma. The chemosensitivity of aneuploid tumor was significantly higher than
      that of diploid.

PMID- 9642345
TI  - [Impulsive angular acceleration evoked middle and long latency potentials in
      guinea pigs].
AB  - Middle and long latency evoked potentials have been successfully recorded in
      guinea pigs with impulsive angular acceleration delivered by a specially
      developed motor. The middle latency responses elicited by impulsive angular
      acceleration had peaks at about 9 ms, 15 ms and 24 ms with a mean peak to peak
      amplitude of about 28muV and the long latency responses after the delivering of
      impulsive angular acceleration in guinea pigs composed of a triphasic wave with a
      mean peak to peak amplitude of about 50 muV occurring during 32 ms to 130 ms with
      respect to the start of head stimuli. A series of experiments lead to the
      conclusion that the middle latency responses to impulsive angular acceleration
      are middle latency vestibular evoked potentials. The long latency response
      elicited by impulsive angular acceleration is not a specific response of auditory
      or vestibular pathway.

PMID- 9642346
TI  - [Studies on the fine structures of inner ear vessels in guinea pigs].
AB  - In order to investigate the characters of inner ear vessels using the
      microvascular corrosion casting technique and scanning electron microscope the
      three-dimensional spatial picture of the vessels in cochlear basilar membrane,
      utriculus, sacculus and three ampullae of guinea pig were observed. It was found
      that arteriole coils were present in the modiolus ampullae, utriculus and
      sacculus. The length of arterioles was therefore prolonged and could keep the
      blood supply in inner ear stable. The possibility of blood coagulation in these
      segments increased because the blood flow became slower here. Another character
      was that the capillary networks appeared denser in stria vascularis and central
      part of the crista, whereas the vessel meshes in basilar membrane of cochlea and
      in planum semiculatum of ampullae were looser. These findings suggested that the
      metabolism in stria vascularis and central part of the crista would be more
      prosperous than that in the basilar membrane and planum semiculatum of ampullae.

PMID- 9642347
TI  - [Application of laser scanning confocal microscopy in inner ear morphological
      studies].
AB  - Laser scanning confocal microscope (LSCM) enables one to observe both the surface
      structure and the inner configuration in the same specimen, by its possibility of
      direct, non-invasive serial optical sectioning of whole mounted specimens. The
      potential value of LSCM in the field of inner ear morphological study was
      evaluated. The configuration of upper parts of organ of Corti was observed with
      the LSCM combined with double-stained fluorescence immunohistochemistry
      technique. The actin filament of hair cells by phalloidin, and the cytokeratin of
      supporting cells by monoclonal pan-anticytokeratin antibody. The stereocilia,
      cuticular plate, and the cuticle-free area of hair cells were well demonstrated.
      In the same specimen, the head plate of outer pillar cell, the phalangeal apical
      plate and the phalangeal process of Deiter cells were clearly showed as well.
      LSCM provide a new tool to the morphological study of organ of Corti.

PMID- 9642348
TI  - [Immunohistochemical study on three peptidergic terminals in nasal mucosa in a
      rat AR model].
AB  - To study the density alterations of three peptidergic terminals in nasal mucosa
      of allergic rhinitis (AR), an exhaustive immunohistochemical sutdy on the changes
      of substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) in nasal mucosa
      was carried out in a toluene-2, 4-isocyanate (TDI)-induced rat AR model. The
      densities of all three tachykininergic terminals in nasal mucosa were
      significantly increased (P < 0.01) in experimental group as compared with control
      group. Increased staining, thickening of peptidergic terminals as well as
      enlargement of varicosities were observed. The increased densities of three
      tachykininergic terminals (SP, NKA and NKB) in nasal mucosa in rat AR model
      indicates that tachykinins play an important role in the pathogenesis of AR.

PMID- 9642349
TI  - [Furosemide test for diagnosis of endolymphatic hydrops: a clinical exploration].
AB  - Furosemide test (FT) is a clinical method for the diagnosis of endolymphatic
      hydrops (EH). Immediately preceding i.v. injection of 20 mg furosemide, a caloric
      test was performed with 50 micromilligrams of water at 30 degrees C.
      Nystagmography was employed to measure the maximum slow velocity of caloric
      nystagmus. The test was repeated one hour after the injection. The two sets of
      data were then compared. An increase beyond 22.97% was defined as positive. The
      first group was composed of 54 patients of EH as the experimental group, and the
      second group 54 patients with vertigo of non-EH as control. The positive rates of
      the two groups were 70.4% and 25.9% respectively. It showed that FT was useful
      for detecting EH. The percentage of directional preponderance (DP) was obviously
      descended in the two groups after i.v. furosemide. Descending rate was 77.8%
      (21/27) in the first group, which had reached the normal value in 9 cases. It was
      showed that DP was important also for criticizing FT. The hearing of all subjects
      was not damaged. When the renal function of the subject was normal and not
      combined with the use of aminoglycoside antibiotics, the dose of FT was not
      dangerous to the hearing and had few side reactions. The mechanism of dehydration
      in hydropic labyrinth was presumed to be acute systemic diuresis, but the effect
      in inner ear was unknown.

PMID- 9642350
TI  - [Otoacoustic emissions and tinnitus].
AB  - Methods of objective tinnitus testing exploration causes of tinnitus and the
      relationship between OAE and tinnitus are reported. In 306 ears with tinnitus
      (with or without hearing loss), Distortion Products Otoacoustic Emission (DPOAE),
      Spontaneous OAE (SOAE) and Transiently Evoked OAE (TEOAE) were tested by ILO92
      Otodynamics Analyzer. Results indicated that 1. In these cases there was no
      correlation between the frequency of tinnitus and SOAE. 2. In 94.8% of
      sensorineural hearing loss with tinnitus the DPOAE-gram presented lower amplitude
      or was absent within the frequency range of elevated pure-tone-thresthold; In 59%
      of cases with normal hearing and tinnitus the amplitude of DPOAE at nearby
      frequencies of tinnitus was decreased and there was no SOAE detectable. At
      frequencies other than that of tinnitus, the amplitude of DPOAE was normal and
      SOAE could be recorded. So OAE could reflect cochlear lesion in early stage.

PMID- 9642351
TI  - [Further comment on surgical approach for hemifacial spasm].
AB  - A new surgical approach for the treatment of hemifacial spasm was carried out in
      110 cases from 1991-1994. The novelty of this new procedure lies in splitting of
      facial nerve by making multiple cuts along the long axis of the nerve-
      descriptively a type of "combing". Among these cases, arachnoid thickening and
      adhesion occurred in 35 cases throughout the vascular course, 66 cases showed
      vascular compression (60%). A segment of vessel could be seen lying between VII
      and VIII cranial nerves in 16 cases. Under the latter circumstance steps taken
      for decompression would be either too risky or impossible. Postoperatively all
      cases got marked improvement or total disappearance of symptoms & signs. Follow
      up varying 1-4 years showed recurrence of symptoms in 6 cases (5.4%). This was
      explaned in light of insufficient splitting. It might be due to lack of
      experience or on account of vascular enclosures. It was suggested that at least
      20 cuts should be made and tested with a minimum of 10mA electric stimulation to
      achieve good result.

PMID- 9642352
TI  - [Endoscopic sinus surgery for the treatment of inverted papilloma of nasal cavity
      and paranasal sinuses].
AB  - Fourteen patients suffering from inverted papilloma of the nasal cavity and sinus
      were operated by the intranasal endoscopic approach. The period of follow-up were
      24-60 months. Only one case had recurrence after three months and was then cured
      by a combined treatment of external nasal approach and radiotherapy. The other 13
      cases had no recurrence in the follow up period. The intranasal endoscopic
      surgical technique was proved a better method for treating inverted papilloma of
      nasal cavity and sinus even when the lesions had affected the posterior ethmoid
      and spenoidal sinuses. It seems that this approrch would be a new way for
      removing inverted papilloma completely and the major advantage of which is an
      incision of the face can be avoided, while the curative rate might be the same or
      even better than that of the external approach.

PMID- 9642353
TI  - [Computed tomography of the ethmoid labyrinth and adjacent structures].
AB  - In order to study the relation of ethmoid labyrinth to the adjacent structures,
      continuous axial CT scan of the ethmoid labyrinth was performed on 9 normal
      subjects. Meanwhile, coronal and axial CT scans of ethmoid labyrinth were
      obtained in 20 normal subjects. On an average, 22 scan sections were done on each
      subject. The relation of ethmoid labyrinth to adjacent structures was observed
      and the remarkable intersubject variations in this anatomic area were noted. The
      relation of posterior ethmoid cells or sphenoid sinus to the optic canal, and the
      relation of internal carotid artery to the sphenoid sinus were clearly
      demonstrated on axial scans. The detailed anatomic structure of the ostiomeatal
      complex and the anatomic relation of ethmoid labyrinth to orbit and anterior
      skull base were revealed by coronal CT scans. CT scan of the paranasal sinuses
      was of great importance in clinical practice for the purpose of etiological
      analysis of sinusitis, design of endoscopic sinus surgery and prevention of
      complication.

PMID- 9642354
TI  - [Current status and prospect of transnasal pituitary tumor operation and cranial
      base surgery].

PMID- 9642355
TI  - [Transseptal re-operation for recurrent pituitary adenoma].
AB  - To summarize the suitable approach for recurrent pituitary adenoma, fifteen
      patients with recurrent pituitary adenoma were re-operated via the transseptal
      sphenoid approach for the second time. During the operation, some degree of
      adhesion was noted in septal mucous membrane. The sphenoid cavity was filled with
      fibrous tissue which has correlated to the methods of reconstructing sellar floor
      during the previous operation. Follow-up study showed satisfactory results. It
      showed that transseptal sphenoid re-operation is still the best approach for
      treating recurrent pituitary adenoma in spite of some degree of operative
      difficulties.

PMID- 9642356
TI  - [Application of nasal endoscopy and cryosurgery in transsphenoidal removal of
      pituitary tumors].
AB  - In order to sum up the experience of transsphenoidal resection of pituitary
      tumors, 60 cases operated between 1984 and 1995 were reviewed. The operation was
      performed via a columella nasi "V" incision and transseptal-sphenoidal approach.
      0 degree and 30 degrees endoscopes were used in 16 cases and the cryotherapy was
      used to destroy the remnant tumor cells in 51 cases. The duration of freezing was
      only one minute each time and it was repeated once again after thawing. The
      advantages of this method were as follows: (1) wider operative field and better
      illumination; (2) magnified operative pictures and TV monitoring; (3) wide and
      changeable visual angle; (4) lack of complications such as hemorrhage, optic
      nerve injury, permanent diabetes insipidus. The proper applications of endoscopy
      and cryosurgery were recommended for transsphenoidal removal of pituitary tumors.

PMID- 9642358
TI  - [Resection of cranial base tumors].
AB  - This article reports 10 cases of cranial base tumors resected by pre-or retro
      auricular intratemporal approach. Among them four were neuronomas, two
      meningiomas, one malignant giant cell tumor of bone, one osteochondnoma, one
      parotid mixed neoplasm and one poorly-differentiated squamors cell carcinoma.
      Total resection in 9 cases and one subtotal resection were performed without
      operative mortality and serious surgical complications. The surgical management
      of cranial base tumor and indications for selecting operative approaches were
      discussed.

PMID- 9642357
TI  - [Transsphenoidal microsurgery for pituitary adenoma: analysis of 3 fatal cases].
AB  - To prevent severe postoperative complications and increase the survival rate of
      patients with pituitary adenoma after transsphenoidal microsurgery, 3 fatal cases
      were analysed in terms of clinical features and caused of death. They included
      (1) the too deeply inserted suction apparatus with resultant midbrain damage; (2)
      bleeding from residual tumor into aphragma sellae and dura mater, entering the
      subarachnoid, causing spasm of the brain vessels. In order to avoid complication,
      it is necessary to follow strictly the rules for transsphenoidal microsurgery and
      improve surgical skills.

PMID- 9642359
TI  - [Effects of growth factors on the survival status and the neurite regeneration of
      auditory neurons in vitro].
AB  - To confirm the biological effects of peptide growth factors on auditory neuron
      (AN) in vitro, the influence of NFG and bFGF on the survival status and the
      neurite regrowth of dissociated primary AN in postnatal chicks was studied with
      serum-free culture technique and cytologic quantitative method. The results
      demonstrated that the growth of non-neuron elements such as Schwann's cell was
      predominant in the earlier stage of culture. The neurite regrowth (bipolarity or
      unipolarity) of AN was observed at 24 hours after seeding. The growth rate
      increase during 48-72 hours in the surviving AN. These findings indicated that
      both growth factors exerted direct neuronotrophic effect on dissociated AN in
      vitro. NGF and bFGF acted in cooperation to promote the axon regeneration of AN.
      The concentration-dependent effect of NGF on neurite regrowth and neurone
      survival was found in the present study. The biological mechanism of NGF and bFGF
      on AN in vitro has been discussed.

PMID- 9642360
TI  - [Effects of ATP on intracellular free [Ca2+]i in isolated cochlear OHC].
AB  - The effect of adenosine triphosphate (ATP) upon intracellular free calcium
      concentration ([Ca2+]i) of cochlear outer hair cell (OHC) isolated from guinea
      pigs was studied. Stained with fluorescence, [CA2+]i was measured using ACAS 570.
      ATP significantly increased the [Ca2+]i level, which then dropped rapidly from
      the peak value it rose again reaction after readdtion of ATP. This result
      indicates that ATP is a nerve transmitter acting on the outer hair cells.

PMID- 9642361
TI  - [Experimental study of streptomycin on 45Ca intake of otolithic membranes].
AB  - 45CaCO3 was injected into guinea pigs, and the radioactivity in otolithic
      membranes of utriculi and sacculi, auditory ossicles and femora was determined by
      liquid scintillation spectrometry, to study the dynamic effect of streptomycin on
      calcium content of otolithic membranes, as a means to explore the mechanism of
      streptomycin ototoxicity. The results showed that otoconium was a dynamic
      structure which took up 45Ca in a time course generally comparable to that of
      bone. Saccular otolithic membranes showed greater intake than utricular
      membranes. The calcium ion concentration of saccular endolymph was greater than
      that of the utriculus and the two maculas were not identical. Streptomycin may
      influence 45Ca uptake in the two macular otolithic membranes, causes calcium
      metabolic disorder and a fall of otolithic calcium content. It is possible that
      the fluid environments of the endolymph have changed, therefore dysfunction of
      otolithic organ may occur. This hypothesis may be one of the explanation of the
      mechanism of streptomycin ototoxicity.

PMID- 9642362
TI  - [The effect of MPS on LAK cell growth and its cytotoxic activity against
      laryngeal cancer (HEP-2)].
AB  - IL-2/LAK adoptive immunotherapy is one of new complementary treatments for
      advanced malignant tumors. This therapy has two main problems: high dose of IL-2
      often causes serious side effects and it is difficult to gain enough amount of
      LAK cells. MPS is a new immunomodulator in cancer immunotherapy. The present
      study showed that, comparing with IL-2 10(6)U/L only, IL-2 2 x 10(5)U/L plus MPS
      0.4mg/L was significantly more effective in activating both the growth of LAK
      cells and its cytotoxicity against HEP-2 cells. And the ratio of CD25 positive
      LAK cells cultured in this condition was also higher. This result suggests that
      MPS plays a role in creasing the membrane receptors of IL-2.

PMID- 9642363
TI  - [Histopathology of the temporal bone in adhesive otitis media].
AB  - To understand the histopathological changes of adhesive otitis media (AOM) in
      human, temporal bone sections processed with the celloidin-embedding technique
      were reviewed. In the 338 pairs of temporal bone specimens, 20 cases (26 ears)
      showed characteristics of AOM. The results showed that the lesions of AOM were
      extensive, involving all middle ear structures including tympanic muscles, round
      and oval windows. There were various pathological changes, in every stage of
      inflammation and tissue repair. According to the main pathological
      characteristics, histopathological changes of the 26 ears were staged as
      exudation, inflammatory grannlation formation, histocyte response and collegen
      proliferation. As the process progressed, the amount of inflammatory cells and
      exudate decreased with the increase of fibroblasts. Certain factors were
      speculated to play an important role in the process of fibrosis. The authors
      analysed the difficulties in the management of AOM and causes of the
      unsatisfactory therapeutic results. Possible measures to improve treatment
      results were proposed.

PMID- 9642364
TI  - [Clinical application of enzyme linked immunosorbent assay in testing antibodies
      against cochlear tissues and nerve tissues].
AB  - Fifty-two patients with idiopathic sensorineural hearing loss and 20 controls
      were examined by enzyme linked immunosorbent assay (ELISA) with cow cochlear
      antigen (CCAg) and cow cochlear nerve antigen (CCNAg). The antibody level against
      CCAg was 0.3811 +/- 0.743 in the control group and 0.9241 +/- 0.2408 in the
      experimental group (OD, x +/- 2s, P < 0.01). Compared with the x +/- 2s antibody
      level of the control group, the antibody level of 24 of 52 (46%) patients of the
      experimental group was positive. The antibody level against CCNAg was 0.2254 +/-
      0.382 in the control group and 0.2331 +/- 0.656 in the experimental group (P >
      0.05). Compared with the x +/- 2s antibody level of the control group, the
      antibody level of 6 of 52 patients (11.5%) of the experimental group was
      elevated. It is suggested that ELISA method can be used as quantitatively in the
      diagnosis of autoimmune inner ear diseases. Moreover, the serum antibodies
      against CCNAg detected in this experiment suggest that some of autoimmune inner
      diseases might be retrocochlear.

PMID- 9642365
TI  - [CT study of the ostiomeatal complex in patients with deviated nasal septum].
AB  - This study was designed to evaluate the influence of nasal septal deviation on
      ostiomeatal complex (OMC). From April 1994 to February 1995, 32 patients with
      deviated nasal septum were investigated by high-resolution CT scan. The results
      showed that (1) 15 patients (15/32) were found to have ipsilateral or bilateral
      ostiomeatal complex disease (OMCD). The incidence of OMCD was related to the
      severity of the septal deviation; (2) measurement of uncinate process angulation
      and ethmoid infundibulum width in patients with OMCD was of limited value; (3)
      the relationship between septal deviation and OMC variation needed further study.
      It has been indicated that for patients with septal deviation coronal CT study is
      necessary to evaluate the degree of OMCD.

PMID- 9642366
TI  - [Outpatient treatment of obstructive sleep apnea syndrome with CO2 laser: laser
      assisted uvulopalatoplasty].
AB  - To find a safe and convenient method for the treatment of obstructive sleep apnea
      syndrome, 89 outpatient cases were treated with CO2 laser-assisted
      uvulopalatoplasty. All cases had been diagnosed and observed with
      polysomnographic monitoring. The result of 89 cases of OSAS was judged as good in
      67 cases (75.7%). Only 6 cases had a little bleeding during operation, no other
      complication has been encountered.

PMID- 9642367
TI  - [Longitudinal evaluation of vocal function following thyroplasty type I for the
      treatment of unilateral vocal paralysis].
AB  - Longitudinal changes of vocal efficiency and stability following thyroplasty type
      I were analysed. Fifty-three patients with unilateral vocal fold paralysis
      underwent vocal function evaluation preoperatively and 1, 3 and 6 months
      postoperatively. Vocal function assessment included videostrobolaryngoscopic
      examination, acoustical and aerodynamic analyses, and perceptual ratings of
      voice. Parameters including glottic gag size, maximum phonation time, glottic
      flow rate, jitter, harmonic to noise ratio, breathness, hoarseness, loudness and
      phrasing showed significant improvement after thyroplasty and remained stable
      within 1 month with only slight fluctuations over a 6 month period. Postoperative
      voice outcome was not affected by age, sex, duration of vocal symptoms, etiology
      of paralysis, or preoperative pulmonary function.

PMID- 9642368
TI  - [A study of LOH on chromosome 9p21 region D9S319 locus of laryngeal carcinoma].
AB  - Loss of Heterozygosity (LOH) on chromosome 9p21 (D9S319) from fifty-four
      laryngeal cancer patients has been examined by using the PCR technique of DNA
      microsatellite markers in this study. The results showed that the LOH on 9p21 was
      100% present (2/2) in in situ carcinomas and 66% (29/44) in invasive carcinomas.
      Therefore, these results suggest that there is a tumor suppressor gene located on
      9p21 region. Its inactivation was related to laryngeal carcinoma and it was an
      early event.

PMID- 9642369
TI  - [Treatment and results of N1 supraglottic laryngeal carcinoma].
AB  - One hundred and eleven cases of supraglottic squamous cell cancer (T1-4N1) were
      retrospectively analysed. The result showed that: 1. the 3 years survival rate
      was 72% (80/111); 2, the rate of contralateral neck node metastasis after
      ipsilateral RND was 17.9%, and the cases of T3-4 with positive histologic
      findings of neck dissection samples had a higher rate contralateral neck node
      metastasis (38.6%); 3, the contralateral neck node metastasis rate (26.1%) in the
      group with surgery alone was significantly higher than that (7.1%) in the group
      with preoperative radiation (P < 0.05). The authors draw the conclusion that
      contralateral neck node metastasis is a high risk factor for recurrence of N1
      supraglottic laryngeal cancer and that preoperative radiation may be be useful in
      controlling subclinical metastasis.

PMID- 9642370
TI  - [Current status and prospects of the study on autocrine and paracrine regulation
      of ovarian function].

PMID- 9642371
TI  - [The secretion and receptor gene of insulin-like growth factor-I quantitative
      expression in ovarian stroma in polycystic ovarian syndrome patients].
AB  - OBJECTIVE: To explore varying different degrees of the action of insulin-like
      growth factor-I (IGF-I) and its receptor gene quantitative expression in the
      ovarian stroma of women with obese and nonobese polycystic ovarian syndrome
      (PCOS). METHOD: The expression of IGF-I receptor gene in the ovarian stroma from
      35 cases of PCOS (obese: 15 cases; nonobese: 20 cases) and 20 cases of control
      were quantitatively determined by reverse transcript polymerase chain reaction
      (RT-PCR) combined with beta(2) micro globlin (beta(2) MG) gene as inner-control
      to amplificate sychronously. The grey value ratio of them were determined. The
      PCR-amplified cDNA fragments were put in restriction analysis (DdeI). RESULTS:
      The expression of IGF-I receptor in PCOS ovary stroma was significantly greater
      than in the control group (P < 0.001). The nonobese group presents more
      enhancement than obese group in IGF-I receptor gene expression. The restrictive
      fragments were same between the PCOS and the control group. CONCLUSIONS: The
      expression of IGF-I receptor in PCOS ovarian stroma is abnormally excessive and
      the nonobese PCOS have more potential action of IGF-I system in ovary stroma.

PMID- 9642372
TI  - [Experimental study on the effect of insulin-like growth factor-I on maturation
      fertilization and cleavage of murine oocytes in vitro].
AB  - OBJECTIVES: To evaluate the effects of insulin-like growth factor-I (IGF-I) on
      the maturation, fertilization, and cleavage of murine oocytes. METHODS: Immature
      and mature murine oocytes were cultured alone or together with murine spermatozoa
      in vitro. Various concentrations of IGF-I were added to the media as experimental
      groups, and was not added as controls. Then the rates of maturation,
      fertilization and cleavage of murine oocytes were observed, and compared between
      the 2 groups. RESULTS: The rates of maturation, fertilization and cleavage of
      murine oocytes in experimental groups were significantly higher than those in the
      controls (P < 0.01 or P < 0.05). Unequal blastomeres and cell fragments were
      observed in both groups, but the differences during the same cultured period were
      not statistically significant (P > 0.05). CONCLUSIONS: IGF-I could induce murine
      oocyte maturation, promote its fertilization and cleavage in vitro, and do no
      harm to the fertilized oocytes and embryos.

PMID- 9642373
TI  - [Application of ultra-short gonadotropin-releasing hormone agonist protocol in
      controlled ovarian hyperstimulation].
AB  - OBJECTIVE: To study the effect of the ultra-short protocol of gonadotropin
      releasing hormone agonist (GnRH-a) combined with human menopausal gonadotropin
      (hMG) regimen for ovarian hyperstimulation. METHODS: Setting clomiphene
      (CC)/human chronic gonadotropin (hCG) (50 cycles, 31 patients) and CC/hmg/hCG
      regimens (16 cycles, 16 patients who had failed in CC/hCG) as control groups, the
      ultra-short GnRH-a/hMG/hCG regimen (15 cycles, 15 patients who had failed in CC
      alone or CC/hMG regimens) as study group, the number of leading follicles,
      endometrial thickness, cervical mucus scores and hormone levels on the day of hCG
      administration, and the pregnancy rates were compared among of these three
      groups. RESULTS: There was no premature luteotropic hormone (LH) surge in the
      ultra-short GnRH-a/hMG/hCG regimen group while there were three cycles in the
      CC/hMg/hCG group. The LH and progesterone (P) levels of ultra-short GnRH-a/hMG
      group on the day of hCG administration were lower than those of CC alone and
      CC/hMG groups. There were more leading follicles, greater endometrial thickness
      and cervical mucus score in the ultra-short GnRH-a/hMG group than those in CC
      alone and CC/hMG groups. The pregnancy rates per cycles in the three groups were
      similar. CONCLUSION: The ultra-short GnRH-a/hMG regimen is a fairly good ovarian
      hyperstimulation regimen, especially for poor responders in CC alone or CC/hMG
      regimens.

PMID- 9642374
TI  - [Expression of transforming growth factor-alpha and myc oncoprotein in the human
      ovary during follicular growth, atresia and corpus luteum formation regression].
AB  - OBJECTIVE: To investigate the expression of transforming growth factor (TGF)
      alpha and myc oncoprotein on human follicular development and atresia in vitro.
      METHODS: Ovarian tissues were obtained from 36 women with regular menstrual
      cycles who underwent abdominal hysterectomy for a variety of gynecological
      conditions. Expression of TGF-alpha and myc protein in the ovarian tissues was
      examined by immunohistochemical technique. RESULTS: In primordial follicale only
      the oocyte showed intense immunostaining for both TGF-alpha and myc oncoprotein.
      Immunostaining for TGF-alpha in granulosa cells and theca interna cells became
      apparent in the follicles of preantral stage. With the increase in the size of
      follicles the intensity of immunostaining in the oocyte decreased, whereas the
      staining intensity of the granulosa and theca cells increased, and persisted in
      the corpus luteum and further intensifying during the midluteal phase. myc
      protein expression in granulosa cells was apparent only in the preantral follicle
      stage. In the regressing corpus luteum, expression of both TGF-alpha and myc
      oncoprotein was restricted only in the peripheral theca lutein cells adjacent to
      the central core of scar issue. In atretic follicles theca interna cells
      exhibited prominent immunostaining for TGF-alpha and myc protein. CONCLUSION: TGF
      alpha and myc oncoprotein combination play a role as intraovarian regulators
      through autocrine and paracrine mechanism and may participate in remodelling the
      initial growth of the oocyte, follicular growth, differentiate and apoptosis.

PMID- 9642375
TI  - [The comparison of clinical and surgical-pathological staging for endometrial
      carcinoma].
AB  - OBJECTIVE: To compare the differences between clinical (FIGO 1971) and surgical
      pathological (FIGO 1989) stagings of endometrial carcinoma and to investigate the
      advantage and the feasibility of the surgical-pathological staging. METHODS:
      Clinical and pathological data of 290 patients with endometrial carcinoma
      surgically treated from 1989 to 1995 were retrospectively reviewed. The clinical
      and surgical-pathologic staging of these patients were compared. The stagings
      were analyzed with regards to the prognostic factors of endometrial cancer.
      RESULTS: The differences between clinical and surgical-pathologic staging in
      stage I and II were 19.7% and 80.5% respectively. 4.2% with metastases to the
      lymph node, 10.6% with positive peritoneal cytology and 60.5% with myometrial
      invasion were found in clinical stage I. 51.4% with metastases to the lymph
      nodes, 46.9% with positive peritoneal cytology and 100.0% of myometrial invasion
      were observed in clinical stage II. The causes of the differences between these
      two staging systems are: (1) it was impossible before operation to accurately
      detect metastases of the lymph nodes and malignant cells in the pelvic-peritoneal
      cavity; (2) when the dilation and curettage was done before operation, the
      lesions of an involved cervix might be missed or an uninvolved cervix
      misdiagnosed as metastatic lesion; (3) there were already cancer cells
      disseminated in the peritoneal cavity. CONCLUSIONS: The surgical-pathologic
      staging defines the real extent of endometrial carcinoma. It is advised that at
      the initial operation attention should be paid to areas beyond the extent of the
      intended surgery itself. During the initial operation, peritoneal cytology and
      pelvic and para-aortic lymph node samplings should be done for the purpose of
      surgical-pathologic staging of the selection of postoperative adjuvant therapy
      and of providing a clinico-pathological basis for the prediction of prognosis.
      Since there is a high percentage of misdiagnosis in clinical stage II endometrial
      carcinoma, special attention is needed in diagnosing and treating such patients.

PMID- 9642376
TI  - [Therapeutic modalities of endometrial carcinoma in stage I and II].
AB  - OBJECTIVE: To evaluate the effectiveness of different therapeutic modalities of
      endometrial carcinoma in stage I and stage II. METHODS: From 1984 to 1992, 205
      patients with endometrial carcinoma in stage I and stage II were treated in our
      hospital. The clinical and pathological data were analyzed retrospectively. There
      were 122 cases in stage I and 83 in stage II. According to therapeutic methods,
      patients could be divided into 4 groups. Group 1 (surgery group): 81 cases; Group
      2 (full dose preoperative intracavitary afterloading irradiation, A point 45G y
      +/- 10%, F point 50 Gy +/- 10%): 62 cases; Group 3 (non-full dose preoperative
      intracavitary afterloading irradiation, doses at both point A and point F less
      than 1/2 of full dose mentioned above): 36 cases; Group 4 (radiotherapy alone):
      26 cases. There were no significant differences in pathological type,
      differential grade, median age and operative methods among the 4 groups. RESULTS:
      The 5-year survival rate of group 1 to group 4 was 83.1%, 96.5%, 84.8% and 62.5%
      respectively in stage I, and 82.0%, 90.9%, 51.4% and 62.7% respectively in stage
      II. The 5-year survival rate was significantly higher in group 2 (P < 0.05).
      CONCLUSIONS: The results suggested that operation combined with full dose
      preoperative intracavitary afterloading irradiation provided the best therapeutic
      effect, whereas non-full dose preoperative intracavitary afterloading irradiation
      showed none of benefit.

PMID- 9642377
TI  - [The relationship between the pathologic features of the uninvolved endometrium
      and prognosis in postmenopausal endometrial carcinoma].
AB  - OBJECTIVE: To investigate the relationship between the pathologic features of the
      uninvolved endometrium and prognosis in postmenopausal endometrial carcinoma.
      METHOD: The clinicopathologic features of 204 cases of endometrial carcinoma were
      analyzed retrospectively, according to the proliferative and atrophic uninvolved
      endometrium, a long term follow-up was done. RESULTS: The patients with
      proliferative uninvolved endometrium (PUE) were more much related with the
      clinical risk factors than those of atrophic uninvolved endometrium (AUE) (P <
      0.001). AUE cases had more virulent types of nonendometrial carcinoma than those
      of PUE (27% vs 5.5%, P < 0.001), and had much worse grade, much deeper myometrial
      invasion and much vascular invasion (P < 0.001). The overall 5-year survival rate
      was 96.7% in the PUE cases and 86.2% in the AUE cases (P < 0.001). CONCLUSION:
      The histopathologic types of the uninvolved endometrium were related to the
      prognosis of the patients with endometrial carcinoma. The patients with
      proliferative uninvolved endometrium had better prognosis than those with
      atrophic uninvolved endometrium.

PMID- 9642378
TI  - [Human leucocyte antigen-DQA1, -DQB1 polymorphism distribution in Shanghai
      Chinese women with pregnancy induced hypertension].
AB  - OBJECTIVE: To explore the mechanism of correlation between human leucocyte
      antigen (HLA) and pregnancy induced hypertension (PIH). METHODS: Oligotyped HLA
      DQA1, -DQB1 locus in 30 Shanghai Chinese PIH families and 14 control families
      were analysed by polymerase chain reaction-sequence specific oligonucleotide (PCR
      SSO) hybridization method (probes labelled by nonradioactive technique). RESULTS:
      Compared with the control group, the allelic frequency of HLA-DQB1 * 0502 was
      significantly higher in PIH couples, and their sharing of HLA-DQA1 increased. No
      difference was found in HLA-DQA1 allelic frequency or HLA-DQB1 sharing in couples
      of the two groups. Analysis of HLA-DQA1 and DQB1 allelic frequency in PIH
      patients and their neonates showed no positive results. CONCLUSION: HLA-DQB1 *
      0502 may be the marker of susceptibility to PIH. The increase of compatibility in
      HLA-D region resulted in decrease of producting blocking antibody. The unbalance
      of maternal-fetal immunity will induce PIH.

PMID- 9642379
TI  - [Oral low-dose magnesium gluconate preventing pregnancy induced hypertension].
AB  - OBJECTIVE: To study the effects of oral low-dose magnesium gluconate in
      prevention of pregnancy induced hypertension (PIH) and its mechanism. METHODS: A
      prospective randomized double-blind study was carried out in 51 pregnant women as
      treatment group (including 22 cases as treatment group 1 and 29 cases as
      treatment group 2) and 51 pregnant women as controls (including 28 cases as
      controls group 1 and 23 cases as control group 2). Low-dose magnesium gluconate
      (3 g/day) or placebo was given from the 28th week of gestation to delivery
      consecutively. RESULTS: 4% of the pregnant women developed PIH after magnesium
      gluconate treatment, which was substantially lower than that in the control group
      (16%) (P < 0.05). In the treatment group 2, women showed higher concentration of
      6-keto-prostaglandin F1 alpha (PGF1a) and 6-keto-/thromboxane B2(TXB2) (P/T)
      ratio than that of the control group 2. Moreover, TXB2 level was lower than that
      in the control group 2. In the treatment group 1 women showed higher ratio of P/T
      than that of the control group 1. There were no significant differences of serum
      magnesium concentration among all groups. CONCLUSION: Low-dose magnesium
      gluconate may efficiently prevent PIH in high risk women. The mechanism of action
      of magnesium gluconate probably involves to keep the balance of PGI2 and TXA2,
      but not associates with serum magnesium level.

PMID- 9642380
TI  - [Glycosylated high density lipoprotein in diabetes related to pregnancy induced
      hypertension].
AB  - OBJECTIVE: To investigate the glycosylation of high density lipoprotein (glc-HDL)
      and its specific binding to human lung fibroblasts (HLF) receptors in gestational
      diabetes woman and to study its relationship with pregnancy induced hypertension
      (PIH). METHODS: The glc-HDL was measured by fluorimetry and the specific binding
      of HDL to HLF receptors was measured with enzyme linked immunoreceptor assay in
      32 gestational diabetic woman group 1, 34 group II, 36 normal pregnant (NP) and
      32 normal non-pregnant (NNP) women. RESULTS: The levels of glc-HDL and the
      intracellular total cholesterol in diabetic pregnant woman group I and II were
      significantly higher than those in the NP and the NNP (P < 0.01). The cell
      binding, internalization and degradation of glc-HDL were higher than that in the
      NP and the NNP. CONCLUSION: The change of HDL level and lipid deposition during
      the process may be one of the causes for arteriole spasm in PIH.

PMID- 9642381
TI  - [The characteristics of labour course and perinatal prognosis in cases of fetal
      persistent occiput-transverse position and persistent occiput-posterior
      position].
AB  - OBJECTIVES: To study the characteristics of the labour course and perinatal
      prognosis in cases of fetal persistent occiput-transverse position (POTP) and
      persistent occiput-posterior position (POPP). METHODS: All the cases, delivered
      with POTP and POPP in or hospital from Nov, 1995 to July 1996 were analyzed
      retrospectively. RESULTS: In abnormal fetal occipital position group, the
      following indices were significantly higher than those of normal group: fetal
      macrosomia, uterine inertia, and duration of each labour course. The speed of
      descending of presentation was obviously slower. The incidence of abnormal labour
      course was markedly increased. The rate of operative delivery was significantly
      higher. The total rate of operative delivery was 82.81% in the POTP group, and
      92.31% in the POPP group. The incidence fetal hypoxia and neonatal asphyxia was
      markedly high in the abnormal occiput group. CONCLUSIONS: The POTP and POPP are
      major cases of dystocia. If management is unsuitable, perinatal prognosis will be
      poor.

PMID- 9642382
TI  - [Relation between fetal intrauterine growth retardation and anticardiolipin
      antibodies].
AB  - OBJECTIVE: To investigate the relationship between fetal intrauterine growth
      retardation and anticardiolipin antibodies. METHODS: Serum anticardiolipin
      antibodies were detected with ELISA method in 5,330 cases of normal gravidas.
      Meanwhile, the observation of immunocomplex depositions in placentas in cases of
      positive anticardiolipin antibodies (ACA) were observed by immunofluorescence
      examination. RESULTS: The positive ACA rate in normal gravidas was 2.70%. The
      incidence of intrauterine growth retardation (IUGR) was 15.28% in cases of
      positive ACA, whereas was 1.77% in cases of negative ACA. There were significant
      differences between two groups (P < 0.001). Among children born in mothers with
      positive ACA, there were 5 cases of positive ACA. Immunocomplex depositions
      (Immunoglobulins & Complements) were all found in placenta of IUGR. CONCLUSIONS:
      ACA could be one of causes of IUGR. Determination of serum ACA would offer a new
      clue to diagnosis and treatment of IUGR.

PMID- 9642383
TI  - [Gonadotropin and autocrone mediated regulation of the ovary].

PMID- 9642384
TI  - [Application of computer in obstetrics].

PMID- 9642385
TI  - [On the conservation and regeneration of Taxus resources].
AB  - In recent years, the taxol isolated from the stem bark of some plants of Taxus
      has been widely as an antitumor agent. But the development of taxol is limited by
      the scarcity of wild Taxus resources. This paper seeks to discuss the ways to
      conserve and promote the regeneration of these resources.

PMID- 9642386
TI  - [Application of adaptive resonance theory network to the quality evaluation of
      radix Sophorae flavescentis].
AB  - ART1 and ART2 models of adaptive resonance theory network have been employed in
      quality evaluation of 40 Radix Sophorae Flavescentis samples collected from
      different regions of China. Based on the UV data of MeOH extract and IR data of
      CHCL3 extract, Shannon information theory has been used for feature selection.
      The results consist with those of traditional appraisal.

PMID- 9642387
TI  - [Analysis and identification of calculus equi components].
AB  - Components of the genuine calculus Equi and false Mabao were analyzed by X-ray
      diffraction. The results indicate that the main components of the genuine Mabo
      are NH4MgPO4.6H2O, NH4MgPO4.H2O and MgHPO4.3H2O, whereas the main components of
      the false Mabao is CaCO3.

PMID- 9642388
TI  - [Influence of processing on quercetin content in flos Sophorae immaturus].
AB  - The HPLC method was applied to determine the quercetin content in Flos Sophorae
      Immaturus. The technology for processing Flos Sophorae Immaturus was selected
      based on orthogonal experiment design. The result has shown that the better
      technology is to bake Flos Sophorae Immaturus for 11 min at the temperature of
      180 degrees C.

PMID- 9642389
TI  - [Effect of processing of the contents of pinoresinol diglucoside in cortex
      Eucommiae].
AB  - The contents of pinoresinol diglucoside in different processed products of Cortex
      Eucommiae were determined by HPLC. The result has shown that the contents of
      pinoresinol diglucoside in post-processed drugs are higher than those in pre
      processed ones.

PMID- 9642390
TI  - [Changes of chemical constituents of radix Sophorae flavescentis in complex
      formulas of traditional Chinese medicine].
AB  - Experiments have been made on the changes of chemical constituents in complex
      formulas of traditional Chinese medicine. The results show that in the complex
      formula containing Radix Sophorae Flavescentis, as affected by various conditions
      of processing such as water, temperature and coexisting reductive substances, the
      content of oxymatrine tends to decrease gradually to disappear while that of
      matrine increase gradually.

PMID- 9642391
TI  - [Water soluble contents of Chinese drug beimu, the bulbs of Fritillaria plants].
AB  - Based on platelet aggregation induced by platelet activating factor (PAF), the
      active fraction with inhibiting effect was screened from four species of Chinese
      drung Beimu, the bulbs of Fritillaria przewalskii, F. ussurienis, F. anhuiensis
      and F. thunbergii. According to the experimental results, the active water
      soluble fraction of F. ussuriensis was further studied. Two nucleosides,
      thymidine and adenosine were isolated. Platelet aggregation assay shows that
      adenosine is the chief aggregation inhibitor with 1% = 42 at 5 microns. It is
      suggested that nucleosides may be the other type of active constituent besides
      alkaloids in the Fritillaria plants.

PMID- 9642392
TI  - [Chemical composition of Craibiodendron henryi W. W. Smith].
AB  - Two components were isolated from the dried leaves of Craibiodendron henryi and
      identified as rhodojaponin II and III by means of IR, MS, 1HNMR and 13CNMR
      spectra. These two compounds are obtained from the herb for the first time.

PMID- 9642393
TI  - [Chemical studies on the root of Salvia trijuga Diels].
AB  - From the root of Salvia trijuga three triterpenoids were isolated. Based on the
      analysis of their spectra, they were identified as coleonolic acid with a
      contracted A-ring, euscaphic acid and 2 alpha-hydroxyursolic acid.

PMID- 9642394
TI  - [Chemical constituents of Ligusticum brachylobum Franch].
AB  - From the roots of Ligusticum brachylobum, which is used as a substitute for
      traditional Chinese medicine Radix Peucedani in the southwest of China, 5
      compounds were isolated and identified as umbelliferone, selinidin, anomalin,
      nodakenin and ferulic acid.

PMID- 9642395
TI  - [Chemical constituents of the root of Boehmeira nivea (L.) Gaud].
AB  - Three compounds were isolated from the root of Boehmeria nivea and elucidated
      according to their spectroscopic data as beta-sitosterol, daucosterol and 19
      alpha-hydroxyursolic acid. They are obtained from the herb for the first time.

PMID- 9642396
TI  - [Determination of loganin in the fruit of Cornus officinalis Sieb. et Zucc].
AB  - A high performance liquid chromatographic method has been developed for the
      determination of loganin in the fruit of Cornus of ficinalis. The method is
      rapid, accurate and sensitive.

PMID- 9642397
TI  - [Effects of ginsenosides from stems and leaves on hyperlipemia induced by
      prednisone acetate in rabbits].
AB  - Rise of total lipid, total cholesterol and triglyceride in rabbits were markedly
      inhibited by oral administration of ginsenosides from stems and leaves at a daily
      dose of 60mg/kg. The inhibitory rates were 66.2%, 92.8% and 58.1% respectively.

PMID- 9642398
TI  - [Effects of saponins from stems and leaves of Panax quinquefolium L. on the
      contraction of rabbit aortic strips].
AB  - It has been found out that the saponins from stems and leaves of Panax
      quinquefolium (PQS) can non-competitively antagonize the dose-response curves of
      norepinephrine (NE), potassium chloride and calcium chloride on the isolated
      aortic strips of rabbits, and obviously inhibit intracellular and extracellular
      Ca2(+)-dependent contraction of the aortic strips induced by NE. These effects of
      PQS are similar to verapamil.

PMID- 9642399
TI  - [Spasmolytic effects of crebanine on isolated gallbladder and Oddi's sphincter in
      vitro].
AB  - The study has shown that the contraction induced by histamine, Ca2+ and K+ in the
      biliary system of guinea-pigs is antagonized by crebanine in vitro. The
      antagonism presents a depression of the maximal response of the dose-response
      curve for the agonists in a non-competitive manner. Crebanine blocks the release
      of calcium from intracellular storage on isolated gall-bladder. The spontaneous
      activity of the oddi's sphincter in vitro is inhibited by crebanine. The initial
      phasic and the ionic contraction induced by K+ (40 mmol/L) in the isolated oddi's
      sphincters of guinea-pigs are inhibited by crebanine.

PMID- 9642400
TI  - [Comparison between Cistanche deserticola Y. C. Ma and C, tubulosa (Shenk) Wight
      on some pharmacological actions].
AB  - The weights of seminal vesicle and prostate gland of castrated young rats were
      significantly increased by administration of alcohol soluble extract from the
      decoction of Cintanche deserticola, C. tubulosa and soaked C. deserticola. The
      phagocytic function of intra-abdominal macrophage in mice was activated by the
      decoction of C. deserticola and C. tubulosa.

PMID- 9642401
TI  - [Compatibility of toxic Chinese medicines].
AB  - This article expounds the suitable compatibility and incompatibility in using
      toxic Chinese medicines in respects of reducing toxicity, raising curative
      effect, enhancing toxicity and reducing curative effect. Meanwhile it discusses
      the compatibility mechanism of toxic Chinese medicines in combination with the
      studies of clinical and modern experiments.

PMID- 9642402
TI  - [Folk medicine of the Qiang nationality].
AB  - Based on a two-year investigation of folk medicine of the Qiang Nationality,
      systematic studies have been made on its formation and development, specific
      methods of physical therapy and experiences and features of clinical application.

PMID- 9642403
TI  - [Detection of konjac glucomannan in seven Amorphophallus Blume species].
AB  - Seven Amorphophallus species were detected for konjac glucomananam (KGM). It has
      been found out that A. albus, A. konjac, A. yuloensis, A. xemengensis and A.
      dunnii are of higher contents of KGM (30%), but A. sinensis and A. yunnanensis
      are not as further comfirmed by TLC analysis. It follows that A. albus, A.
      konjac, A. yuloensis, A. xemengensis and A. dunnii are high quality resources of
      KGM, but A. sinensis and A. yunanensis cannot be used as substitutes for the
      above-cited five species.

PMID- 9642404
TI  - [Rules of the absorption, distribution and translocation of nitrogen, phosphorus
      and potassium in turmeric plant].
AB  - It has been found out that the percentages of nitrogen (N), phosphorus (P) and
      potassium (K) in turmeric plant (Curcuma longa) are higher in young organs.
      Varying with the growth stages, the nutrient contents of the plant, whose amount
      order is K > N > P are the highest in the seedling stage. Nutrient absorption
      occurs mainly in the young turmeric forming stage and enriching stage. Nutrient
      translocation takes place mainly from leaves and leaf stalks to young and old
      turmeric, the rate of P being the highest.

PMID- 9642405
TI  - [Callus induction of Coptis species and generation of alkaloids].
AB  - Callus induction and tissue culture of six medicinal Coptis species have been
      carried out and a comparative analysis of berberine, jatrorrhizine, coptisine,
      palmatine and epiberberine in calli and crude drugs have been made by TLC and
      HPLC.

PMID- 9642406
TI  - [HPLC analysis of mimic vinegar-processed yuanhuacine].
AB  - In this paper, the variation of yuanhuacine samples after vinegar-processing and
      hydrolysis has been analyzed by HPLC. The result has shown that the content of
      yuanhuacine decreases hearly 22% after mimic vinegar-processing. Also this
      procedure has brought a new compound-hydrolytic product of yuanhuacine, whose UV
      lambda max is 264nm. The research work is to be continued.

PMID- 9642407
TI  - [Selection of technology for processing steamed Garcinia hunburyi with high
      pressure].
AB  - The technology for processing steamed Garcinia hunburyi with high pressure was
      synthetically selected by using orthogonal experiment design, based on the
      indexes of anti-inflammatory, bacteriocidal, anti-tumour effects and gambagic
      acid content. The result shows that the best way is to steam for 0.5 h at 126
      degrees C.

PMID- 9642408
TI  - [Comparison of 4 extraction methods for antidotal granules of Coptis].
AB  - Four extraction methods for Antidotal Cranules of coptis were compared, with
      berberine, barcalin and gardenoside taken as the indexes. The result shows that
      the total contents of three components appear in the following order: semi-bionic
      extraction > semi-bionic extraction with precipitation with alcohol > extraction
      with water > extraction with water plus precipitation with alcohol.

PMID- 9642409
TI  - [Chemical constituents of Eclipta alba (L.) Hassk].
AB  - Ecliptasaponin C (1), a new triterpenoid glucoside, was isolated together with
      daucosterol (2) and stigmasterol-3-O-glucoside (3) from Eclipta alba. Based on
      spectral analysis, chemical evidence and hydrolytic results, it's structure was
      deduced as 3-beta-O-beta-D-glucopyranosyl-19beta-hydroxy olean-12-ene-28-oic acid
      28-O-beta-D-glucopyranoside, Compounds 2 and 3 were obtained from Eclipta for the
      fist time.

PMID- 9642410
TI  - [Chemical constituents of Aralia fargesii Franch].
AB  - From the EtOH extract of Aralia fargesii, 8 compounds were isolated and
      identified as umbelliferone, esculetin, scopoletin, scoparone, oleanic acid,
      falcarindiol, mellissic acid and beta-sitosterol.

PMID- 9642411
TI  - [Chemical constituents of Aster albscens Hand.-Mazz].
AB  - Four compounds, stigmasterol, D-hurulon-14-en-3-ol, stigma-delta7.22-dien-3beta
      palmitate and friedelin were isolated from the root of Aster albscens for the
      first time. Their structures were elucidated by spectral methods.

PMID- 9642412
TI  - [Determination of paeonol in the root of Cynanchum paniculatum (Bge.) Kitag. by
      gas chromatography].
AB  - A method for the determination of paeonol in the root of Cynanchum paniculatum by
      macro-reticular resin-GC has been established. The experimental result shows that
      the standard curve is linear in the detection range and the recovery is 99.42%
      (RSD = 2.28%, n = 5).

PMID- 9642413
TI  - [Determination of nodakenin in the rhizome or root of Notopterygium incisum Ting
      by TLC-scanning].
AB  - TLC-scanning was applied to the determination of nodakenin in the rhizome or root
      of Notopterygium incisum from three different producing areas. The correlation
      coefficient was 0.9997, recovery 97.5% and relative standard deviation 1.96%.

PMID- 9642414
TI  - [Immunological regulation of rhizoma Imperatae on IL-2 and T-lymphocyte
      subpopulation].
AB  - The present study has proved that rhizoma imperatae can significantly raise the
      phagocytic rate and index in experimental mice, as well as the number of T(H)
      cells, and in the meantime facilitates the generation of interleukin-2. This
      indicates that rhizoma imperatae is markedly conducive to the enhancement of
      immunologic function of mice.

PMID- 9642415
TI  - [Effects of ding zhi pills on the scopolamine-induced impairment of passive
      avoidance in rats].
AB  - The Ding Zhi Pills described in "Thousand-Golden-Prescriptions" have better
      memory improving effect than those described in "Prescriptions People's Welfare
      Pharmacy". A combination of Poria, Radix Polygalae and Rhizoma Acori Graminei
      could enhance the pharmacologic effect of Radix Ginseng. Cinnabaris, described in
      "Prescriptions People's welfare Pharmacy", as one of the compositions in Ding Zhi
      Pills, does not improve the impairment of learning and memory, and therefore
      seems to have no meaning in the Ding Zhi Pills.

PMID- 9642416
TI  - [The Selaginella tamariscina (Beauv.) Spring complex in the treatment of
      experimental diabetes and its effect on blood rheology].
AB  - Experiments have revealed that in treating rats for diabetes induced by alloxan,
      the Selaginella tamariscina complex injection given intraperitoneally (25g/kg)
      for 12 days helps lower the levels of blood sugar and serum lipid peroxide, as
      well as increase the concentration of serum insulin. Histologic observation has
      shown that this injection could repair the structure of pancreatic inlet B cells
      injured by alloxan.

PMID- 9642417
TI  - [Protective effects of radix Salviae miltiorrhizae on azathioprine hepatotoxicity
      in rats].
AB  - The changes of liver function and malondialdehyde (MDA) and glutathione (GSH)
      were studied in rats intoxicated with azathioprine (Aza) 15mg/(kg.d) and in rats
      treated with Aza mixed Salviae 8g/(kg.d). The results showed that in the Aza
      group, the levels of ALT, AKP, MDA increased and GSH decreased significantly in
      week 1 and week 2. But in the Salviae group the levels of ALT, AKP, MDA decreased
      and GSH increased significantly, approaching the normal levels, It follows that
      Salviae has protective effects on Aza hepatotoxicity in rats.

PMID- 9642418
TI  - [Anti-inflammatory and analgesic effects of scolopendra from different habitats].
AB  - The water extracts of several species of the Chinese drug scolopendra from
      different habitats can inhibit obviously the increased permeability of abdominal
      blood capillaries and ear inflammation in mice. They can also raise the pain
      thresholds in mice during hot-plate and writhing tests. Their toxicity is very
      low.

PMID- 9642419
TI  - Clinical psychology students' self-reported willingness to interact with persons
      living with HIV.
AB  - Previous research has indicated that health care workers, including those in
      mental health, have negative attitudes toward people living with HIV and AIDS and
      may be unwilling to work with them in a professional capacity. Ajzen's theory of
      planned behavior (1985) was used as a model for better understanding the specific
      components of these attitudes. In this project doctoral students in clinical
      psychology read a vignette describing a person who is HIV positive and then
      completed a set of measures regarding willingness to interact professionally,
      level of knowledge and attitudes toward HIV and AIDS, and attitudes regarding
      drug abusers and promiscuity. Results indicated that participants were generally
      willing to provide therapy for an HIV positive client, although some participants
      indicated that they would experience some anxiety in doing so. Level of anxiety
      could be predicted by attitudes toward AIDS and whether the participants believed
      that accepting an infected client would have negative effects for them personally
      or professionally.

PMID- 9642420
TI  - Evaluation of the effectiveness of AIDS health education interventions in the
      Muslim community in Uganda.
AB  - In 1992 the Islamic Medical Association of Uganda designed an AIDS prevention
      project and conducted a baseline survey prior to community level activities.
      Results of that baseline were previously reported in this journal. During 2 years
      of prevention activities in local Muslim communities, 23 trainers educated over
      3,000 religious leaders and their assistants, who in turn educated their
      communities on AIDS during home visits and at religious gatherings. After 2
      years, there was a significant increase in correct knowledge of HIV transmission,
      methods of preventing HIV infection and the risk associated with ablution of the
      dead and unsterile circumcision (p < 0.001). There was a significant reduction in
      self-reported sexual partners among the young respondents less than 45 years. In
      addition there was a significant increase in self-reported condom use among males
      in urban areas (p < 0.001). Collaboration between health professionals and
      religious leaders can be achieved and can contribute to the success of AIDS
      prevention efforts.

PMID- 9642421
TI  - Erotized, AIDS-HIV information on public-access television: a study of obscenity,
      state censorship and cultural resistance.
AB  - This study analyzes court records of a county-level obscenity trial in Austin,
      Texas, and the appeal of the guilty verdict beginning with a Texas appellate
      court up to the U.S. Supreme Court of two individuals who broadcast erotized AIDS
      and HIV safer sex information on a public-access cable television. The trial and
      appellate court decisions are reviewed in terms of argument themes, and the
      nature of sexual value controversy is outlined. Erotic materials often conflict
      with broad-based sexual and community values, and providing erotized HIV and AIDS
      information products can be a form of radical political action designed to force
      societal change. This study raises question as to how this trial and this type of
      informational product might affect the programs and activities of information
      resource centers, community-based organizations, libraries, and the overall
      mission of public health education.

PMID- 9642422
TI  - "Extramarital" sex: is there an increased risk for HIV transmission? A study of
      male couples of mixed HIV status.
AB  - This report describes the sexual behavior with "extramarital" partners of men who
      are in committed relationships with men of opposite HIV status. We examined the
      rates of unprotected anal sex with outside partners and compared these rates with
      the prevalence of such activity within the couple, during the year prior to the
      assessment. Seventy-five couples were interviewed, of whom 50 (67%) reported sex
      outside of the primary relationship by one or both members of the couple. Rates
      of unprotected anal sex with one-night stands and "other" partners were 25% and
      33%, respectively among men who engaged in anal sex with such partners. In
      contrast, 54% of the men who engaged in anal sex with their primary partner did
      not always use condoms. Data from men who engaged in anal sex with both their
      primary partner and one-night stand(s) revealed that condoms were used less
      frequently within the primary relationship when the HIV negative men were the
      insertive partner; otherwise the rates of unprotected anal sex were similar.
      Approximately 75% of HIV negative men who engaged in receptive anal sex always
      used condoms, and a similar proportion of HIV positive men always used condoms
      during insertive anal sex, regardless of partner type. The vast majority of
      unprotected anal sex occurred without ejaculation inside the rectum. Unprotected
      oral sex was highly prevalent regardless of partner type. Implications for public
      health policy and primary prevention research are discussed.

PMID- 9642423
TI  - Gender differences in injection-related behaviors among injection drug users in
      Baltimore, Maryland.
AB  - Baseline data from 640 injection drug users in the Stop AIDS for Everyone study,
      an HIV preventive intervention were used to examine gender differences in self
      reports of injection behaviors. In both the bivariate and multivariate analyses
      men reported injecting alone, in semipublic areas, and at their mother's
      residence more often than women. In the bivariate analyses, women reported denser
      personal networks, and in the multivariate analyses, women reported significantly
      greater overlap between their drug and sex networks. These data suggest that this
      overlap of sex and drug networks may reduce women drug injectors' ability to
      adopt and maintain HIV protective behaviors. The data also suggest that
      interventions need to address gender differences in the social context of risk
      behaviors.

PMID- 9642424
TI  - Gender and AIDS-related psychosocial processes: a study of perceived
      susceptibility, social distance, and homophobia.
AB  - Over the past decade, researchers have accumulated evidence that suggests six
      main factors are associated with AIDS-related risk reduction behavior: (a)
      perceived susceptibility (Dolcini et al., 1995; van der Plight & Richard, 1994);
      (b) attitudes toward condoms (Catania et al., 1994; Maticka-Tynadale, 1991); (c)
      personally knowing someone with HIV/AIDS (Joseph et al., 1987); (d) perceived
      peer norms about risk-reduction (Maticka-Tyndale, 1991); (e) previous sexual
      activity (Joseph et al., 1987); and (f) self-efficacy (Aspinwall, Kemeny, Taylor,
      & Schneider, 1991; van der Plight & Richard, 1994). Furthermore, there is some
      suggestion that the epidemiology and sociocultural constructions of the disease
      has led to considerable gender, racial, and class differences in awareness of
      AIDS, perception of HIV threat, and HIV-relevant behavior (Cohan & Atwood, 1994;
      Dolcini et al., 1995; Gillies, 1994).

PMID- 9642425
TI  - Homophobia, self-esteem, and risk for HIV among African American men who have sex
      with men.
AB  - Qualitative data from individual interviews with 18-29 year old African American
      men, who have sex with men (n = 76) were used to examine the relationship of
      negative attitudes toward homosexuality, self-esteem, and risk for HIV.
      Respondents perceived members of their communities as holding negative attitudes
      toward homosexuality, and many thought the African American community was less
      accepting of homosexuality than the white community. There was evidence that
      these negative attitudes are internalized by some of the young African American
      men themselves. Respondents mentioned several ways that negative attitudes toward
      homosexuality could lead to lower self-esteem and psychological distress in young
      gay and bisexual men. In addition, respondents articulated several mechanisms by
      which low self-esteem and psychological distress might be associated with sexual
      behaviors that put one at risk for HIV. We concluded that addressing and changing
      society's negative views of homosexuality are important components of a
      comprehensive approach to reducing the transmission of HIV, especially among
      young people in communities of color.

PMID- 9642426
TI  - HIV prevention among Asian and Pacific Islander American men who have sex with
      men: theories, research, applications, and policies. Introduction.

PMID- 9642427
TI  - Epidemiology of HIV and AIDS among Asian and Pacific Islander Americans.
AB  - As of June 1997 the Centers for Disease Control and Prevention reported 4,370
      AIDS cases among Asian and Pacific Islander Americans (APIs) in the U.S. It also
      reported that the rate of new AIDS cases among APIs men who have sex with men
      (MSM) per 100,000 population increased by 55% from 1989 (4.0) to 1995 (6.2).
      Focusing on the relatively low numbers of APIs with AIDS in the U.S. has resulted
      in complacency among API communities and government officials, despite reports of
      increased seroprevalence and exponential growth in diagnosed AIDS cases. However,
      because of the geographic and social isolation of many Asian and Pacific Islander
      American communities, the effect of HIV is magnified once it takes hold. The low
      numbers of reported AIDS cases among API and the perception of them as the "model
      minority" has reinforced their denial of AIDS as a threat. Data collection and
      surveillance tools must be modified to accurately capture the range of HIV
      related and social issues that affect Asian/Pacific Islander communities in the
      United States. Notwithstanding sample limitations, ethnic-specific data are
      needed to identify HIV trends in each of the Asian Pacific Islander American
      communities, which can inform prevention and intervention programs.

PMID- 9642428
TI  - HIV prevention among Asian and Pacific Islander American men who have sex with
      men: a critical review of theoretical models and directions for future research.
AB  - Nationally, the incidence of AIDS is increasing at a higher rate among Asian and
      Pacific Islander American men who have sex with men (API MSM) than among white
      MSM. Furthermore, current HIV prevention efforts are inadequate to slow the
      rapidly rising HIV epidemic in the gay API community, and little attention has
      been paid to the applicability of existing behavior change models to APIMSM. This
      paper reviews the five major models of health behavior change used in HIV
      prevention for the MSM population: the health belief model, theory of reasoned
      action, social learning theory, diffusion theory, and the AIDS risk reduction
      model. Although some of these models have been useful in designing risk reduction
      programs for API MSM, recent empirical data suggest that the models do not
      adequately address environmental influences affecting API MSM and limit our
      choices in prevention strategies to the level of the individual. We propose an
      ecological model for health promotion as a potentially useful theoretical
      framework, and suggest prevention strategies directed at the individual, the
      family, the general API community, and the mainstream gay community to reduce HIV
      risk among API MSM.

PMID- 9642429
TI  - HIV seroprevalence, risk behaviors, and cognitive factors among Asian and Pacific
      Islander American men who have sex with men: a summary and critique of empirical
      studies and methodological issues.
AB  - The goals of this article are to (a) summarize and discuss published empirical
      studies addressing HIV seroprevalence rates and HIV-related behaviors and
      cognitive factors among Asian and Pacific Islander American (API) men who have
      sex with men (MSM) in the United States, (b) examine existing population-based
      research methodologies for studying HIV and AIDS prevention, (c) describe a
      conceptual framework to facilitate the identification of ecologically sound or
      culturally appropriate and competent methodologies for studying HIV prevention
      among API MSM, and (d) discuss methodological issues and recommend alternative
      methodologies to better understand this population in HIV prevention. A total of
      eight published empirical studies reported the HIV seroprevalence rates, HIV-risk
      behaviors, and attitudes toward HIV and AIDS among API MSM. Specifically, seven
      studies reported HIV seroprevalence rates that were based on either self
      disclosure of HIV status or HIV test results among the study participants. Four
      studies also reported findings about the relationships between HIV-related
      behaviors and cognitive factors. There are five population-based databases on HIV
      and AIDS epidemiology and surveillance which have been managed by the Centers for
      Disease Control and Prevention. Findings from the seven studies indicate that API
      MSM are as likely to engage in HIV-risk behaviors as other groups. The present
      analysis reveals that conventional surveillance or epidemiological techniques
      (e.g., random digit telephone dialing), based on a singular model of populations,
      are not appropriate to address culturally, linguistically and racially/ethnically
      diverse groups of API MSM. To address the diversity of this group, ecologically
      sound or culturally appropriate and competent research methodologies are needed.
      Thus, a conceptual framework for such methodologies with examples was reviewed.
      Two alternative methodologies, network analysis and venue-based sampling, were
      briefly discussed.

PMID- 9642430
TI  - Asian and Pacific Islander American HIV community-based organizations: a
      nationwide survey.
AB  - A national survey was conducted to (a) ascertain the status of HIV prevention
      among community-based organizations targeting APIs in the United States, (b)
      define technical assistance needs among these organizations, and (c) determine
      their involvement in the HIV community planning process. Of the 80 surveys sent
      out, 49 (61%) completed responses were received. Filipinos, Chinese, Vietnamese,
      Cambodians, and multiracials were the subpopulations targeted the most often,
      and, not surprising, Tagalog, Cantonese, Mandarin, Vietnamese, Cambodian, Korean
      and Japanese were the Asian languages most widely in use. Gay men, bisexual men,
      and youth were targeted most frequently by HIV prevention efforts. Of all the
      largest ethnic subpopulations, Asian Indian is the only group with no community
      based organization that exclusively targets them for HIV prevention. More than
      95% of respondents reported conducting some type of evaluation; the size of the
      budget and organization often determined the evaluation strategies used. Program
      development, staff development, and program evaluation were the most frequently
      reported areas of technical assistance requested. A majority of the respondents
      (79%) reported being involved with the HIV prevention community planning process
      where APIs were represented on state/local community planning groups, they did
      not rate the performance of the community planning process highly. We recommend
      providing technical assistance in fund-raising, program evaluation, and
      participation in the HIV community planning process.

PMID- 9642431
TI  - A profile of six community-based HIV prevention programs targeting Asian and
      Pacific Islander Americans.
AB  - Based on a framework (i.e., research and evaluation, prevention and services, and
      advocacy and policy), the goal of this article is to profile six community-based
      HIV prevention programs targeting Asian and Pacific Islander (API) Americans,
      especially among men who have sex with men. These six programs were chosen based
      on one or more of the following three criteria: (a) epidemiological profiles of
      AIDS cases among Asian and Pacific Islander Americans, (b) ethnic diversity, and
      (b) community development among Asian and Pacific Islander Americans in the fight
      against HIV. The six programs are (a) the Kokua Kalih Valley Health Center,
      Honolulu; (b) the Asian and Pacific Islander Wellness Center, San Francisco; (c)
      the Asian Pacific AIDS Intervention Team, Los Angeles; (d) the Asian and Pacific
      Islander Coalition on HIV and AIDS, New York City; (e) the AIDS Services in Asian
      Communities, Philadelphia; and (f) the Massachusetts Asian AIDS Prevention
      Project, Boston. The present analysis reveals that five programs have their roots
      in the gay or bisexual communities. Two programs have existed for about 3 years
      (the epidemic is going into its 17th year). Major financial support for the six
      programs are federal, state, or county sources; private support is generally
      minimal. All six programs offer a wide range of culturally competent and
      linguistically appropriate prevention activities and services (including two
      national projects) targeting a diverse API population. However, gaps in services
      exist in the younger programs. In addition to a paucity of epidemiological,
      surveillance, and empirical data, most reported that barriers fall into one or
      two interrelated categories: (a) structural (e.g., lack of governmental or
      private funding) or (b) cultural (e.g., denial of risk, homophobia, fear of
      confidentiality). These findings suggest that HIV prevention activities and
      services for Asian and Pacific Islander Americans should be based on empirical
      and cultural data, and that API Americans should become more actively involved in
      social and political activities. Asian and Pacific Islander American agencies are
      challenged to integrate HIV with other health and social issues pertinent to the
      communities.

PMID- 9642432
TI  - Asians and Pacific Islanders and HIV prevention community planning.
AB  - Since 1993, the Centers for Disease Control and Prevention (CDC) has required
      state and local health departments to engage in a community planning process and
      to develop HIV prevention plans to spend federal HIV prevention funds. This
      analysis reviews the HIV prevention plans from 29 states, 5 local governments,
      and 6 Pacific Island jurisdictions (61.5% percent response rate). The plans from
      these 40 jurisdictions reflect the uneven implementation of HIV prevention
      community planning efforts and the uneven progress is achieving CDC's core
      objectives for HIV prevention community planning. Specifically, Asians and
      Pacific Islanders (APIs) often are not represented in state and local HIV
      prevention community planning groups. There also are significant gaps in the
      manner in which HIV and AIDS surveillance data are collected and reported for
      APIs. Finally, API populations are rarely included in HIV prevention priorities.

PMID- 9642433
TI  - Will MCP-1 and RANTES take center stage in inflammatory diseases including
      asthma?

PMID- 9642434
TI  - Mediastinal fibrosis presenting as asthma.
AB  - Asthma is one of the most common chronic medical conditions affecting children.
      The usual presenting symptoms of asthma include wheezing, shortness of breath,
      and dyspnea on exertion. Occasionally, children who present with one of these
      respiratory complaints have a less common disorder. Mediastinal fibrosis is a
      rare and incurable condition in which an excessive fibrotic reaction in the
      mediastinum causes progressive cardiopulmonary compromise. The presentation is
      variable: many patients present with respiratory symptoms such as cough,
      wheezing, dyspnea, and/or hemoptysis, while others are asymptomatic and present
      with a mediastinal mass discovered incidentally on a radiograph. With such a
      broad array of presenting complaints, and a clinical course characterized by slow
      progression of symptoms, the early stages of mediastinal fibrosis can mimic other
      diseases such as asthma, chronic bronchitis, or the superior vena cava syndrome.
      In this report we describe two patients with mediastinal fibrosis who were
      initially thought to have asthma.

PMID- 9642435
TI  - Postmortem serum levels of tryptase and total and specific IgE in fatal asthma.
AB  - Sera were obtained postmortem from 55 subjects classified into three groups;
      death due to asthma (FA, n = 21), asthmatic but death not due to asthma (NFA, n =
      24) and a nonasthmatic control group (NAC, n = 10). A full autopsy was performed
      on all cases and a medical history, including details of allergies, was obtained
      by questionnaire from the next of kin. Grading of asthma severity by either
      questionnaire or autopsy was comparable (tP = 0.435, p > 0.05) and the mean
      pathology-grade was significantly higher for the FA group (3.375) compared to the
      NFA group (2.375), p < 0.05. Tryptase was elevated (> 2.0 micrograms/L) in 21/55
      sera (38%) and there was no significant difference between the groups. ROC plots
      showed that tryptase levels did not discriminate between the FA and NFA groups,
      even if specimens were collected within 24 hours after death. Total IgE was
      significantly elevated in the FA group (geometric mean 140.3 kU/L) compared to
      the other two groups (NFA 30.2 kU/L, NAC 9.4 kU/L), p = 0.05. Fatal asthmatics
      also had a greater positivity (67%) to a screen for common inhalant allergens
      than did the other groups (NFA 30%, NAC 20%). Sera with a positive screen were
      tested against a panel of 10 common aero-allergens. Each sample was then assigned
      a number (N) and a score (S), dependent on either the number of allergens
      positive (N) or the total sum of pluses for all allergens (S). Both the N and S
      values were higher for the FA group (N = 98, S = 264) than the NFA group (N = 52,
      S = 151) and NAC group (N = 4, S = 8). The ratio (S/N) which gives an index (I)
      was 2.69, 2.90, and 2.00, respectively. Tryptase was poorly correlated to the
      total IgE level (r = 0.036); however, mean values for N and S were significantly
      different (N 6.81, S 4.50, and N 19.25, S 11.5, p < 0.05) for sera with tryptase
      levels < 2.0 or > or = 2.0 micrograms/L, respectively. We conclude that total and
      specific IgE may be useful predictors of asthma severity but that postmortem
      tryptase is not useful in the diagnosis of a fatal asthmatic attack.

PMID- 9642436
TI  - Effectiveness and safety of fexofenadine, a new nonsedating H1-receptor
      antagonist, in the treatment of fall allergies.
AB  - Fexofenadine HCl is a new, nonsedating H1-receptor antagonist approved for
      treatment of seasonal allergic rhinitis (SAR). In a double-blind, randomized,
      placebo-controlled, multicenter trial, 588 patients with fall SAR rated the
      severity of their symptoms using a scoring system at a screening visit and during
      a 3-day placebo lead-in period. Patients who did not respond to placebo and met
      symptom severity criteria were randomized to receive placebo or fexofenadine HCl
      at 40, 60, or 120 mg bid at 7:00 a.m. and 7:00 p.m. for 14 days. Patients
      continued to rate the severity of their symptoms immediately before receiving
      each dose (at trough). A total of 545 patients were included in an intent-to
      treat analysis. The change from baseline in the primary efficacy variable
      (average daily 7:00 p.m. reflective symptom scores) was significantly greater in
      patients receiving all dosages of fexofenadine HCl than placebo (p < 0.01). All
      active dosages produced significant decreases (p < 0.05) in secondary end points:
      7:00 a.m. reflective symptom scoring; 7:00 a.m. and 7:00 p.m. scoring 1-hour
      before dose; and bedtime scoring 1-3 hours after the 7:00 p.m. dose. All dosages
      of fexofenadine HCl were well tolerated, and no effect on QTc was observed. In
      conclusion, fexofenadine HCl is safe and effective in the treatment of fall SAR,
      with 60 mg bid being the optimal therapeutic dosage.

PMID- 9642437
TI  - Asthma among the famous. Erwin Schrodinger (1887-1964), Austrian physicist.

PMID- 9642438
TI  - Asthma among the famous. Padre Pio (1887-1968), Italian Roman Catholic Cleric.

PMID- 9642439
TI  - Asthma among the famous. Edmund C. Blunden (1896-1974), British poet, biographer,
      and literary critic.

PMID- 9642440
TI  - Asthma among the famous. Howard Thurman (1900-1981), American minister, educator,
      and author.

PMID- 9642441
TI  - Static DNA cytometry as a diagnostic aid in effusion cytology: I. DNA aneuploidy
      for identification and differentiation of primary and secondary tumors of the
      serous membranes.
AB  - OBJECTIVE: To determine whether DNA aneuploidy is a sensitive and specific marker
      for the identification of tumor cells in effusions and whether the pattern of DNA
      aneuploidy can provide important information for the differential diagnosis of
      primary and secondary tumors of the serous membranes. STUDY DESIGN: One hundred
      eight malignant mesotheliomas as well as 102 metastatic carcinomas of the serous
      membranes were obtained from routine cytologic and histologic material. One
      hundred reactive effusions were investigated as controls. Nuclear DNA contents
      were measured after Feulgen staining using a TV image analysis system. RESULTS:
      DNA aneuploidy was assumed if abnormal DNA stemlines, a coefficient of variation
      of the first DNA stemline > or = 10%, or cells > 9c were observed. On this basis
      the prevalence of DNA aneuploidy in mesotheliomas was 83% for cytologic and 84%
      for histologic material. In effusions of metastatic carcinomas it was 100%. None
      of the 100 reactive effusions revealed DNA aneuploidy (prevalence, 0%). Positive
      predictive value for mesotheliomas was 100%; negative predictive value was 88%
      for cytologic and 82% for histologic material. Positive predictive value for
      metastatic carcinomas was 100%; negative predictive value was 100%. Seventy-two
      percent of the mesotheliomas revealed their greatest stemline within the range
      1.80c-2.20c, whereas none of the metastatic carcinomas showed this stemline
      position. CONCLUSION: DNA image cytometry might be a very sensitive and highly
      specific, additional tool for identification of neoplastic cells in effusions as
      well as for the differential diagnosis of mesothelioma vs. metastatic carcinoma
      of the serous membranes.

PMID- 9642442
TI  - Static DNA cytometry as a diagnostic aid in effusion cytology: II. DNA aneuploidy
      for identification of neoplastic cells in equivocal effusions.
AB  - OBJECTIVE: The sensitivity of conventional cytology for identification of
      neoplastic cells in effusions is unsatisfactory, about 58%. The rate of
      diagnostically equivocal effusions in routine cytology is about 6%. DNA
      aneuploidy has previously been proven to be a sensitive and specific marker for
      the identification of tumor cells in effusions. In the present study we
      determined if malignancy can be identified in cytologically equivocal cells in
      effusions using DNA aneuploidy as a marker, thus decreasing the rate of
      cytologically equivocal diagnoses in effusions. STUDY DESIGN: One hundred
      cytologically equivocal effusions of the serous cavities were obtained from
      routine diagnostic material. Nuclear DNA content was measured after Feulgen
      staining using a TV image analysis system. Data were correlated with patient
      follow-up. RESULTS: DNA aneuploidy was assumed if abnormal DNA stemlines, a
      coefficient of variation of the first DNA stemline > or = 10% or cells > 9c were
      observed. The sensitivity of DNA aneuploidy for the identification of malignancy
      was 55.9%. Specificity of DNA nonaneuploidy for benignity was 94.1%. The positive
      predictive value of the marker DNA aneuploidy for the occurrence of malignant
      cells was 97.9% since all but one DNA aneuploid case showed malignancy in follow
      up. CONCLUSION: Image cytometry applying DNA aneuploidy as a parameter is able to
      detect the occurrence of malignant cells in cytologically equivocal effusions in
      about every second case. Thus, this method is able to increase diagnostic
      accuracy of conventional effusion cytology by decreasing the rate of
      diagnostically equivocal effusions.

PMID- 9642443
TI  - Characteristics of perisinusoidal collagenization in liver cirrhosis: computer
      assisted quantitative analysis.
AB  - OBJECTIVE: To determine the respective roles of septal fibrosis,
      necroinflammatory activity, iron deposition, steatosis, and patterns of nodular
      and septal remodeling in the collagenization of the perisinusoidal space in
      livers from patients undergoing transplantation for alcoholic or posthepatitis C
      cirrhosis and to ascertain whether perisinusoidal collagenization has clinical
      implications added to those of septal fibrosis. STUDY DESIGN: Sixty-six
      hepatectomy specimens from patients undergoing liver transplantation for
      cirrhosis were analyzed. Thirty-two alcoholic and 34 posthepatitis C cirrhoses
      were included. Picro Sirius-stained slides were examined with polarized light and
      the amount of perisinusoidal collagenization measured by computerized image
      analysis. Size distributions of septa and nodules were assessed by mathematical
      morphology methods. RESULTS: The septal and perisinusoidal fibrosis indices and
      Knodell and Pugh-Child scores showed significant differences between alcoholic
      and posthepatitis cirrhoses. Correlation between septal fibrosis and
      perisinusoidal collagenization was weak, though significant. Both variables
      correlated significantly with the clinical score. The correlation was negative
      between septal fibrosis or perisinusoidal collagenization and the Knodell score.
      CONCLUSION: Perisinusoidal collagenization was not a feature of all cases of
      cirrhosis, although it was more prominent in alcoholics. For the whole series, it
      significantly correlated with the clinical score, which increased significantly
      when high perisinusoidal collagenization was added to high septal fibrosis. No
      absolute dependence was found between perisinusoidal collagenization and septal
      fibrosis; percentage of slender fibrous septa and amount of iron deposition were
      other factors entered in the regression equation.

PMID- 9642444
TI  - Image cytometry of breast carcinomas that are DNA diploid by flow cytometry: time
      to revise the concept of DNA diploidy?
AB  - OBJECTIVE: To investigate whether breast carcinomas found to be DNA diploid by
      flow cytometry (FCM) are still diploid if reassessed by image cytometry (ICM).
      STUDY DESIGN: In a series of 286 breast cancers analyzed by FCM there were 100
      (35%) cancers that were classified as DNA diploid. Fourteen of the 100 diploid
      cases were selected for further analysis with ICM because the patient had died of
      breast cancer within 11-84 months after the diagnosis (a group with unfavorable
      outcomes), and 19 cases were selected at random from the cases who had no
      recurrence of cancer during follow-up of six or more years (a favorable group).
      RESULTS: Eleven (33%) of the 33 cases turned out to be DNA nondiploid, with a DNA
      index > or = 1.2 when analyzed by ICM. Nine of the 11 DNA aneuploid samples by
      ICM were found among the 14 patients with unfavorable prognoses and only 2 among
      the 19 patients with favorable outcomes (P = .002). The five-year survival rate
      of the women with DNA diploid cancer by both methods was 86%, whereas that of
      patients with DNA aneuploid cancer by ICM was 36% (P = .002). CONCLUSION: The
      results show that some breast carcinomas classified as DNA diploid based on FCM
      are not DNA diploid by ICM and that such carcinomas are associated with poorer
      outcomes than the ones that are DNA diploid also by ICM. The prognostic
      significance of DNA ploidy in breast cancer may need to be reexamined in studies
      where both FCM and ICM are used.

PMID- 9642445
TI  - Diagnostic value of AgNOR staining in thyroid cytology.
AB  - OBJECTIVE: To determine the value of the argyrophil nucleolar organizer region
      (AgNOR) technique on scrape cytology of thyroid lesions. STUDY DESIGN: AgNOR
      counts were evaluated in smears of 70 thyroid lesions that were sent for frozen
      section and included 15 cases of follicular adenoma, 10 cases of follicular
      carcinoma, 13 cases of papillary carcinoma, 23 cases of nodular goiter and 9
      cases of Hashimoto's thyroiditis. Forty-one slides out of 70 were freshly
      prepared, and 29 slides had been previously stained with hematoxylin and eosin
      and then destained with alcohol. The number of AgNOR dots was recorded for 50
      cells, and the mean number was calculated. RESULTS: The mean AgNOR counts were
      statistically significantly higher in malignant lesions in comparison to benign
      lesions. CONCLUSION: AgNOR staining could be of use in cytologic material from
      thyroid lesions.

PMID- 9642446
TI  - Role of planimetric analysis in diagnosing thyroid follicular lesions on fine
      needle aspiration biopsies: a study with histologic correlation.
AB  - BACKGROUND: Follicular lesions represent a gray area of interpretation in fine
      needle aspiration biopsy (FNAB) of the thyroid, with as much as 25% inconclusive
      reports. We identified "predominantly follicular lesions" (PFLs) as the cytologic
      category most apt to take advantage of planimetric analysis to reach a more
      definitive diagnosis. STUDY DESIGN: Sixty-eight cases of FNAB were diagnosed as
      PFL among the 1,296 FNABs submitted to our institution between January 1994 and
      June 1995. These cases underwent planimetric analysis with a Leica semiautomatic
      image analyzer. A smear from a colloid nodule was used as a reference slide.
      Nuclear areas, perimeters, form factors and maximum diameters were evaluated.
      Cases in which nuclear areas and maximum nuclear diameters values were found to
      be > or = 30% higher than the corresponding values found in the reference slide
      were reported to the clinician as suspicious for malignancy ("flagged" by the
      computer). These cases required closer follow-up with repeat FNAB within a month,
      ultrasound and nuclear imaging studies. Nineteen of these cases underwent
      surgical resection. RESULTS: Histologic reports diagnosed 9 cases of follicular
      carcinomas, 4 cases of follicular adenomas and 6 cases of nodular hyperplasia.
      When nuclear areas, perimeters and maximum diameters were all utilized, all the
      malignant lesions were reported correctly by the computer analysis as flagged,
      and all the benign lesions were reported as "not flagged." The sensitivity and
      specificity were 100%, and statistically significant correlations were proven.
      CONCLUSION: Although the above data provide strong evidence for the value of
      planimetric analysis in differentiating between follicular lesions, we cannot
      reach definitive conclusions on the basis of such a limited number of cases.
      However, the results stimulated our current efforts in applying planimetry along
      with the evaluation of other biologic markers to a larger set of cases.

PMID- 9642447
TI  - Computer-assisted histometric analysis of tissue-engineered ovine bone.
AB  - OBJECTIVE: To develop a computer-assisted histometric technique that
      quantitatively determines the amount of regenerating bone, while excluding
      fibrovascular tissue and void spaces, in tissue-engineered bone constructs. To
      this end, a histometric technique was developed that couples digital tiling with
      adaptive, multiband color thresholding (AMBCT). STUDY DESIGN: To test the
      technique, a previously described model bone tissue-engineered construct filled
      with morcellized bone graft was employed. Histometric techniques were applied to
      quantify the amount of bone formed following eight weeks of implantation.
      RESULTS: The histometric technique was able to yield quantitative information
      regarding the amount of bone despite intrahistologic and interhistologic
      differences in staining. The technique is user friendly and highly automated. In
      addition to area fractions, the technique can provide bone ingrowth profiles as a
      function of geometry and implantation time. CONCLUSION: Digital tiling coupled
      with AMBCT offers an easy, fast and reproducible technique that aids in
      quantification of bone within histologic sections. In addition, the technique can
      be adapted to quantification of other tissues. Further studies are under way to
      investigate the potential of correlating the histometric technique with
      mechanical strength analyses of tissue-engineered bone specimens.

PMID- 9642448
TI  - Prognostic value of stem cell line identification for renal cell carcinomas.
AB  - OBJECTIVE: To investigate the prognostic value of nuclear DNA content (DNA ploidy
      level) in a series of 95 renal cell carcinomas (RCCs). STUDY DESIGN: Eight
      variables were used to characterize DNA ploidy levels. They included DNA index
      and seven others characterizing the presence of specific stem cell lines in each
      of the 95 RCCs under study. All these variables were determined by means of
      computer-assisted microscopy applied to Feulgen-stained nuclei. The actual
      information contributed by each of the eight variables was determined by means of
      univariate statistical analyses. RESULTS: The results showed that in the DNA
      ploidy-related eight variables, the presence of at least 4% aneuploid nuclei with
      > 5C DNA content was associated with the most significant prognostic value in
      RCCs with intermediate (T2, T3) invasion levels. CONCLUSION: The present study
      clearly showed that stem cell line characterization, and particularly the
      presence of highly aneuploid cells (with > 5C DNA content), is associated in RCCs
      with significant prognostic value. This kind of marker may help the
      identification of patients who will develop metastases after surgery and for whom
      adjuvant therapy might thus be indicated.

PMID- 9642449
TI  - Prognostic significance of DNA ploidy and S-phase fraction in malignant serous
      cystadenocarcinoma of the ovary.
AB  - OBJECTIVE: To determine the prognostic value of DNA ploidy and S-phase fraction
      in malignant serous cystadenocarcinoma of the ovary. STUDY DESIGN: Flow
      cytometric analysis of nuclear DNA content was performed on paraffin-embedded
      tissues of 31 serous cystadenocarcinomas of the ovary. DNA ploidy, DNA index and
      S-phase fraction were determined without knowing the final outcome in the
      patients. RESULTS: Histograms in 14 (46%) cases were aneuploid, whereas 17 (54%)
      were diploid. Aneuploidy was more frequent at the advanced stages of the disease
      as well as in the poorly differentiated histologic types. However, ploidy had a
      prognostic influence: both the disease-free survival and overall survival were
      better in diploid than aneuploid tumors at early and advanced stages. S-phase
      fraction (SPF) could be correctly assessed in 19 cases (62%) and was > 15% in 21%
      (4 cases). The survival of those patients, however, was not significantly
      different from that of those with SPF < 15%. CONCLUSION: If used as an adjunct,
      DNA ploidy is of value in predicting tumor behavior, response to chemotherapy and
      disease recurrence.

PMID- 9642450
TI  - DNA quantification as a prognostic factor in gastric adenocarcinoma.
AB  - OBJECTIVE: To determine if DNA quantification, studied in cytologic samples
      obtained by fiberendoscopy, has predictive value in gastric adenocarcinoma. The
      survival times of patients in whom the tumor was the cause of death were
      considered variables of interest. STUDY DESIGN: Twenty-nine patients with gastric
      cancer, diagnosed by cytology, endoscopy and microbiopsy, were selected. The
      study was done over more than 10 years. Smears were stained with progressive
      hematoxylin and processed by computer for DNA evaluation by image cytometry.
      RESULTS: Four different types of histograms that directly relate to tumoral
      malignancy were obtained. These histograms were characterized by the value of
      entropy. We established four grades of aggressiveness. Then we obtained two large
      groups: high and low grade of malignancy. We studied the survival times in both
      groups and constructed a Kaplan-Meier survival curve for the high grade of
      malignancy group. We confirmed the results statistically and found that there was
      a significant relationship, with P < .05. CONCLUSION: The use of DNA
      quantification by image cytometry is strongly advised in daily surgery as a
      prognostic indicator of survival time in gastric adenocarcinoma patients.

PMID- 9642451
TI  - Sialadenosis of parotid gland: a cytomorphologic and morphometric study of four
      cases.
AB  - BACKGROUND: Sialadenosis is recurrent, noninflammatory, nonneoplastic enlargement
      of salivary glands usually associated with an underlying systemic disorder.
      CASES: Fine needle aspiration was performed on four patients with bilateral,
      painless parotid swellings. The cytologic picture was distinctive and identical
      in all the cases. Smears revealed clusters of swollen acini and numerous naked
      nuclei of acinar origin in the background. There was absence of inflammatory
      cells. Diagnosis of sialadenosis was made in each case. Morphometric measurements
      were performed using an ocular micrometer. Results indicated a significant
      increase in mean acinar diameter in a sialadenotic gland as compared to a normal
      gland (76.03 microns vs. 53.79 microns). CONCLUSION: Cytomorphologic features of
      sialadenosis are distinctive enough to enable its diagnosis on fine needle
      aspiration. It is important to be aware of this entity as most cases do not
      require surgical intervention.

PMID- 9642452
TI  - Antisperm antibodies in men with psychogenic anejaculation.
AB  - Antisperm autoantibodies were determined in 16 men suffering from psychogenic
      anejaculation who underwent assisted reproduction treatments. Blood and semen
      samples were collected after transrectal electroejaculation and antisperm
      antibodies in serum and on the surface of motile spermatozoa were measured using
      the direct and indirect immunobead binding test. Five men (31%) were found
      positive for antisperm antibodies. The majority of antibodies were directed
      against the sperm heads. Surface antibodies were mainly IgA isotype whereas serum
      antibodies were IgG isotype. These results suggest that psychogenic anejaculation
      might be associated with increased incidence of antisperm autoimmunity.

PMID- 9642453
TI  - Birth after electroejaculation coupled to intracytoplasmic sperm injection in a
      gun-shot spinal cord-injured man.
AB  - We describe the case of a man who, after a gun-shot wound, has become paraplegic.
      As a consequence of his spinal cord injury he developed infertility due to
      incomplete erection and anejaculation. After several unsuccessful penile
      vibratory stimulation attempts, it was possible to achieve ejaculation by means
      of transrectal electrostimulation. However, the total sperm motility count, the
      percentage of normal sperm morphology, and the vitality and hypo-osmotic swelling
      test scores were rather low, and in particular viability was strikingly decreased
      during sperm preparation. These parameters further decreased following
      electroejaculate, forcing us to use intracytoplasmic sperm injection instead of
      conventional in vitro fertilization for the treatment cycle. A normal pregnancy
      was achieved which resulted in birth of a healthy girl on 1st January 1997.

PMID- 9642454
TI  - Effects of cigarette smoking on semen characteristics of a population in Mexico.
AB  - A study of semen quality was conducted in 197 smoking and 161 non-smoking men
      undergoing initial infertility investigation. The men were allocated into groups
      according the number of cigarettes smoked per day < 10 (n = 57), 11-20 (n = 115),
      and > 20 cigarettes (n = 25). Smokers had significantly poorer sperm density (P <
      .005), a lower percentage of viability (P < .007), a lower percentage of normal
      sperm morphology (P < .005), and the percentage of motile sperm was lower (P <
      .005). These parameters were worse in the heavy smoking groups. Thus the present
      study corroborates reports of detrimental effects of cigarette smoking on sperm
      characteristics. Further studies are needed to explain the mechanism by which
      smoking affects spermatogenesis.

PMID- 9642455
TI  - A neuropeptide in human semen: oxytocin.
AB  - The neuropeptide oxytocin (OT) has been detected in testis and epididymis of
      several mammals. The peptide affects steroidogenesis and sperm transport in vivo.
      Effects of OT on sperm motility in vitro seems to be contradictory. As no data
      are available on the presence of OT in human semen and on the relationship of OT
      with sperm characteristics, we assessed OT level in semen samples in 3 groups of
      patients: (I) normozoospermic, (II) astheno-/oligo-/teratozoospermic, and (III)
      azoospermic subjects. Furthermore, we studied the relationship between the
      concentration of OT in semen and the sperm characteristics. OT was measured in
      seminal plasma by radioimmunoassay after extraction. OT semen levels did not
      differ in control patients (I: 1.72 +/- 0.78 pg/mL; n = 10), patients with poor
      semen quality (II: 1.66 +/- 0.91 pg/mL; n = 11), or in vasectomized patients
      (III: 1.28 +/- 0.65 pg/mL; n = 11). No statistically significant relationships
      between the OT levels and sperm characteristics (density: 0.0693; total sperm
      count: 0.0845; percentage of motility: 0.1341; morphology: 0.3478) have been
      found. The neurosecretory peptide oxytocin is present in human seminal plasma of
      normal as well as of vasectomized subjects. OT is not only derived from the
      testis; OT levels in poor semen samples are not different from controls. No
      relationship was found between OT seminal plasma levels and sperm
      characteristics.

PMID- 9642456
TI  - Thyroid gland and epididymal sperm motility in rats.
AB  - The purpose of this research was to investigate the effect of hypofunction of the
      thyroid gland, caused by radioactive suppression of the gland, on the pattern of
      spermatozoa motility in different segments of the rat epididymis. Thyroidectomy
      was obtained by i.p. infection of 270 microCi of I-131. After about 30 days, the
      animal reached hypothyroidism as determined by serum level of T4. When the
      motility pattern of the sperm obtained from the epididymis of normal rats was
      compared to that of hypothyroid animals, a drop in the parameter of path velocity
      (VAP), progressive velocity (VSL), and track speed (VCL) were detected.
      Hypofunction was associated with decreasing sperm motility in the epididymis. In
      thyroidectomized rats injected with T4, no sperm motility changes were observed.

PMID- 9642457
TI  - Declining sperm count and fertility in males: an epidemiological controversy.
AB  - There have been several suggestions from different populations that sperm count
      has decreased in the past 20 years. Concerns have, however, been raised in the
      interpretation of these findings, particularly with regards to subject selection
      mechanisms and data-analysis. Furthermore, these findings are inconsistent with
      the reports that male infertility rates have remained constant during the past 3
      decades. The increased number of men seeking consultation on infertility may only
      be the result of the tendency of couples to delay pregnancy and the increased
      availability of treatment. Moreover, sperm concentration is not always in itself
      the determinant of male fertility, so the use of sperm count as an indicator of
      male infertility in epidemiological studies should be considered with caution.

PMID- 9642458
TI  - Unaltered protein pattern/genital tract secretion marker levels in seminal plasma
      of highly viscous human ejaculates.
AB  - SDS-PAGE (12.5%) analysis and neutral alpha-glucosidase, fructose, and zinc level
      assessment were carried out in seminal plasma of 20 patients with highly viscous
      ejaculates and of 20 control subjects, with the aim to investigate the relations
      between high consistency of semen and epididymal, vesicular, and prostatic
      secretions. Very low sperm motility was observed in all the patients' ejaculates,
      both normo- and oligozoospermics. Protein patterns obtained in control and highly
      viscous semina showed similar protein bands, in the range of 10-100 kD.
      Furthermore, unaltered seminal neutral alpha-glucosidase, zinc, and fructose
      level were measured in the same specimens. These results indicated no impairment
      of epididymal, vesicular, and prostatic function in patients with hyperviscous
      semina, while their normal electrophoretic seminal protein profile suggested
      unaltered genital fluid interactions during the semen coagulation-liquefaction
      process.

PMID- 9642459
TI  - Loss of left testicular volume in men with clinical left varicocele: correlation
      with grade of varicocele.
AB  - It is reported that a clinical left varicocele is associated with loss of
      ipsilateral testicular volume. We have examined the loss of left testicular
      volume in infertile men with clinical left varicocele using ultrasound-derived
      measurements of testicular volume. We have reviewed the testicular volumes,
      maximum internal spermatic vein diameters, and the clinical reports of 404 men
      presenting for infertility evaluation at our institution between 1992 and 1996.
      Men with bilateral or subclinical varicoceles were excluded from the study.
      Subclinical varicoceles were diagnosed by the ultrasonographic demonstration of
      one or more veins having a maximal diameter of more than 3 mm. In men with
      clinical left varicocele, mean left testicular volume was less than right
      testicular volume (12.7 vs. 13.8 mL, P < .001). This finding was not observed in
      men without varicocele (12.3 vs. 12.6 mL, P > .05). In men with left varicocele,
      the difference between right and left testicular volume (right minus left)
      increased with increasing varicocele grade. Our data demonstrate that a left
      varicocele is associated with loss of left testicular volume. The results also
      show that the degree of left testicular hypotrophy is proportional to the
      clinical grade of the varicocele.

PMID- 9642460
TI  - Interleukin-6 in seminal plasma of fertile and infertile men.
AB  - Cytokines released by various cell subsets in the male urogenital tract are
      capable of markedly influencing sperm function and fertility. Interleukin-6 (IL
      6) levels were determined by "sandwich" enzyme immunoassay in the seminal plasma
      of 77 men divided as follow: (1) into 7 groups according to the etiological
      diagnosis of fertility, and (2) into 2 groups on the basis of normal or abnormal
      spermiogram. There was a statistically significant association between IL-6 and
      the patients' status (P < 0.0014). These results are due to statistically
      significant differences between the groups with infection of the accessory
      genital glands and normal controls, as well as between the groups with infection
      of the accessory genital glands and that with varicocele, indicated by the
      Honestly Significant Differences (HSD) test for multiple comparisons. There was
      no significant difference of IL-6 levels between men with normal and those with
      abnormal spermiograms. Furthermore, there was no correlation between IL-6 levels
      and the variables of the spermiogram. The prostate seems to be the main site of
      origin of IL-6 in the seminal plasma. Our data suggest that urogenital infections
      may lead to elevated levels of IL-6 in the seminal plasma. This measurement of IL
      6 in semen may provide clinically useful information for the diagnosis of male
      accessory gland infection.

PMID- 9642461
TI  - Testicular histology in experimental uremic rats.
AB  - Testicular histology in chronic renal failure was studied using stepwise
      nephrectomized and adenine-treated rats. Serum levels of urea nitrogen and
      creatinine were significantly higher than those in sham-operated and control rats
      (P < .001). However, the mean tubular diameter was not different among the 4
      groups. Numbers of A-spermatogonia, preleptotene and pachytene spermatocytes, and
      spermatids per 100 Sertoli cells were not different among the 4 groups. It would
      appear that testicular histology is not influenced by chronic renal failure in
      rats.

PMID- 9642462
TI  - Germ cell apoptosis and endothelial nitric oxide synthase (eNOS) expression
      following ischemia-reperfusion injury to testis.
AB  - There is evidence to suggest that reactive oxygen species (ROS) are involved in
      ischemia-reperfusion injury to the testis. Nitric oxide (NO), a ubiquitous free
      radical produced by the nitric oxide synthases (NOS), has been implicated in
      physiologic and pathologic interactions with ROS. We examined the effect of
      testicular ischemia on germ cell apoptosis and endothelial NOS (eNOS) expression.
      Adult rats were subjected to unilateral 720 degrees testicular torsion for 1 or 3
      hours and 24 hours later, testes were harvested for immunohistochemical studies.
      Apoptosis was detected by in situ 3' end-labeling of DNA with digoxigenin-ddUTP
      and eNOS protein was detected using an eNOS monoclonal antibody. Tests subjected
      to 3 hours of torsion had a threefold increase in apoptotic germ cells per cross
      sectional area compared to sham testes (P < .05). In addition to its known
      expression in Leydig, Sertoli, and vascular endothelial cells, eNOS was detected
      in the cytoplasm of degenerating germ cells. Consecutive testis sections stained
      for eNOS and cellular DNA fragmentation demonstrated co-localization of eNOS
      protein and germ cell apoptosis. The detection of strong immunostaining in
      apoptotic germ cells supports a role of eNOS in germ cell degeneration after
      testicular ischemia-reperfusion and suggests that NO is associated with germ cell
      apoptosis.

PMID- 9642463
TI  - [Surveillance and prevention of animal rabies in the world].
AB  - The author examines in turn methods and results for surveillance and control of
      rabies in animals. Surveillance is essentially carried out by collecting
      laboratory results from diagnoses of rabies in animals through direct
      immunofluorescence in the sample or after mouse inoculation or inoculation in
      cell cultures. Due to technical and financial constraints, the results collected
      are usually insufficient in number, particularly in developing countries.
      Surveillance of rabies is thus often based on data obtained from a non-target
      species (human beings). Disease prophylaxis varies according to whether rabies is
      found in wildlife or domestic animals. In both cases, there is at present a
      tendency to abandon methods of sanitary prophylaxis by reducing the number of
      vector-animals (fox, stray dogs, cats, bats, etc.), and instead to introduce
      medical prophylaxis by preventive vaccination. As a result, oral vaccination has
      already given spectacular results in the fight against rabies in foxes, and could
      also be used for dogs. The author specifies the conditions for applying this
      vaccination.

PMID- 9642464
TI  - [Human African trypanosomiasis, contributions of experimental models].
AB  - Melarsoprol has remained the chosen drug for the late-stage treatment of human
      African trypanosomiasis (HAT) due both to Trypanosoma brucei (T.b.) gambiense and
      T.b. rhodesiense; however, arsenical encephalopathies, which are often fatal,
      occur in 5-10% of the treated cases. To date, two major problems have not been
      solved. The first one is the precise diagnosis of early involvement of the
      central nervous system (CNS) which determines the therapeutics to be
      administered. The second one is linked to the lack of data on in vivo efficacy of
      products which are effective in vitro against trypanosomes. Answers have to be
      provided by experimental animal models of HAT. Such models would allow for better
      studies of the pathology and pathogenesis of the disease, as well as therapeutic
      trials of potentially effective new drugs or combinations. We have developed
      acute and chronic murine and sheep experimental animal models of HAT infected by
      T. b. brucei. Meningoencephalitis and neurological signs are relatively difficult
      to obtain in murine models and require artificial means, such as suramin
      treatment on day 21 after-infection. The chronic murine model has demonstrated
      CNS involvement with meningitis, followed by meningoencephalitis with progressive
      astrocytosis. The sheep model develops a disease with CNS complications and
      cerebrospinal fluid can be collected. In the sheep model, we have described anti
      galactocerebrosides antibodies, which represent major components of myelin, which
      may indicate an autoimmune process in the CNS. We then described these antibodies
      in the cerebrospinal fluids and sera from patients at a late-stage of the
      disease. From a therapeutic point of view, we have cured mice or sheep with low
      doses of melarsoprol, or with the nitroimidazole derivatives Ro 15-0216 and
      megazol, alone or combined with suramin. Further studies of these nitroimidazole
      compounds, which could be proposed for human use, have to be carried out on a
      primate model infected by T.b. gambiense. To our knowledge, this primate model is
      not available. This is why we have recently developed a T. b. gambiense primate
      model of HAT on Cercopithecus aethiops.

PMID- 9642465
TI  - [Fluctuations of serotonin and its metabolites in the lung and intestinal mucosa
      in the rat infected with Nippostrongylus brasiliensis].
AB  - The influence of parasitism on host biogenic amine levels was investigated in
      Nippostrongylus brasiliensis infected rats. Amine levels were estimated in
      tissues surrounding Nematods in their biological environment: the lung and
      intestinal mucus. D0 being the day of infestation, tissues were obtained at 24,
      30 and 45 hrs, and every day between D4 and D14 (when the rat was completely
      deparasited by the self-cure phenomenon). Biogenic amines belonging to the
      serotoninergic pathway were quantified by HPLC with electrochemical detection. In
      the lungs and mucus, parasitism resulted in an important decrease in serotonine
      (5-HT) and 5-hydroxyindolacetic acid (5-HIAA) levels, as opposed to the immediate
      5-HT precursor, the 5-hydroxy-tryptophane (5-HTP). Host response to parasitism is
      translated by serotoninergic pathway levels. This leads to two hypotheses: 5-HT
      turn-over may be accelerated, but the inhibition of 5-HT synthetic enzyme, 5
      hydroxytryptophane hydroxylase, by the parasite present in the host seems more
      probable.

PMID- 9642466
TI  - [Optimization of parasitological diagnosis of human intestinal microsporidiosis].
AB  - The diagnosis of microsporidiosis by staining stools is known to be fast and
      cheap. To obtain a specific and sensitive result, two colorimetric methods must
      be used: staining by the fluorochrome Uvitex 2 B (VAN GOOL) and trichrome. Among
      the four staining methods of trichrome currently studied, the WEBER coloration
      could be considered as the most efficient. The density of microsporidia spores
      could be semi-quantitatively evaluated, because their distribution is
      homogeneous.

PMID- 9642467
TI  - [Dynamics of Plasmodium falciparum gametocytemia as a function of therapeutic
      response to chloroquine in a mesoendemic malaria zone].
AB  - Patients with Plasmodium falciparum infections were selected with an in vivo
      chloroquine sensitivity assay in a mesoendemic area of Senegal. Gametocytemia was
      studied in relation to asexual parasite responses classified as drug-sensitive or
      showing RI or RII resistance. Gametocyte prevalence and density appeared
      significantly higher in resistant infections than in sensitive ones. These
      observations were made on children as well as on adults. The period between first
      clinical symptom appearance and treatment, varying from 0 to 5 days, was not
      linked to asexual parasite responses, but was significantly and positively
      correlated to gametocyte prevalence and density observed seven days after
      beginning the treatment. The comparison between these results and those
      previously observed in a hypoendemic area suggests that the dynamic of
      gametocytemia is independent of the endemic level. These observations illustrate
      that the dissemination of chimioresistant malaria can be reinforced--via the
      gametocyte stage--by selective chloroquine pressure.

PMID- 9642468
TI  - [Localized cutaneous leishmaniasis due to Leishmania infantum MON-1 contracted in
      northern Algeria].
AB  - Classically, the agent of the sporadic skin leishmaniasis in Northern Algeria is
      Leishmania infantum MON-24. This paper reports the first documented observation
      of localized cutaneous leishmaniasis due to Leishmania infantum zymodeme MON-1 in
      Northern Algeria. The interest of using the Western blot serological analysis to
      guide the diagnosis and the usefulness of the hamster inoculation to isolate
      Leishmania from pauciparasitized lesion is demonstrated.

PMID- 9642469
TI  - [Apropos of 1 case of hepatogastric fascioliasis in Cape Verde].
AB  - The authors report a case of Fascioliasis sp. distomiasis with a double hepatic
      and gastric location primitively associated with a gastric cancer metastazed to
      the liver. The parasitic origin of the lesions suspected from the histological
      specimen of the gastric biopsy (the presence of eggs) was confirmed by serology
      with the presence of the arc 2 specific to immunoelectrophoretic analysis, while
      the parasitological examination of the stools was always negative. The patient
      grew well after a day's cure of triclabendazole (375 mg x 2). Although the
      ectopic locations of Fascioliasis are classic, they are usually in the abdominal
      wall, less frequently in the gastric or colic wall. The fact that the
      contamination originated on the Cape Verde is indiscutable, since the patient had
      never left the island. It is the 5th case described in medical literature, thus
      confirming the presence of Fasciola hepatica (or gigantica) on the islands of the
      Cape Verde, whose population is of both Portuguese and African origin and has
      kept the eating habits of the former colonial power (Portugal is a zone of high
      endemicity for human fascioliasis). It would be interesting to look for Limnaea
      and contaminated bovine on the Cape Verde islands.

PMID- 9642470
TI  - [Apropos of 1 Ivoirian case of osseus and cutaneous histoplasmosis by Histoplasma
      capsulatum var. duboisii].
AB  - Humeral, tibial and cutaneous localizations of Histoplasma capsulatum var.
      duboisii were observed on a 6 year old boy. The diagnosis was made possible by
      anatomo-pathological and mycological examinations. Treatment with terbinafine was
      administrated for 4 months. The boy recovered without after-effects in the tibial
      localization, but did suffer after-effects in the humeral localization.

PMID- 9642471
TI  - [Primitive psoas abscess in children; diagnostic difficulties and non surgical
      treatment: apropos of 2 cases].
AB  - From an analysis of two files of children carriers of primitive psoas abscess,
      the authors report the difficulties of diagnosis due to the rarity of this
      affection and the similarities of its symptomatology with ostearthritis of the
      hip which is a common pathology at the pediatric surgery unit of C.H.U. Yopougon
      (Republic of Cote d'Ivoire). A non surgical treatment made of antibiotherapy and
      traction fixed in the axis of the limb is proposed, since it helped the two
      patients who had presented an echographical stage II of psoas abcess to recover
      without after-effects.

PMID- 9642472
TI  - [A case of asplenia in a sickle cell homozygote SS patient].
AB  - One case of total splenic atrophy is reported in a patient with SS homozygous
      sickle-cell disease presenting no related malformation, thus recalling the
      IVEMARK syndrome. An abdominal echography and computed tomography are
      indispensable in order to confirm the absence of the anatomic spleen; this makes
      for a better follow-up of sickle-cell disease.

PMID- 9642473
TI  - [Histoplasma capsulatum histoplasmosis: apropos of 1 case observed in the
      internal medicine department of the CHU of Treichville (Abidjan)].
AB  - The advent of AIDS has resulted in an increase in diseases which were previously
      rare. In HIV-infected subjects, histoplasmosis takes a disseminated and
      particularly severe form, with a fatal outcome in our country, the more so
      because the clinical presentation resembles tuberculosis and is generally treated
      as such. The authors report a case of disseminated histoplasmosis in a patient
      dually-reactive to HIV-1 and HIV-2, in whom the clinical presentation was fever,
      mediastinal lymphadenopathy and pulmonary infiltrates. The diagnosis of
      histoplasmosis was made at autopsy.

PMID- 9642474
TI  - [Cutaneous lesions, viral risk and marine bird ticks, a world wide problem;
      apropos of 1 case with pseudo-zoster lesions].
AB  - Dermatological injuries provoked by tick bites deserve more attention. The
      authors present the clinical observation of a young woman bitten in Brittany by
      the marine bird associated tick Ornithodoros (A.) maritimus and presenting pseudo
      zoster skin lesions. Two other individuals working together with the patient and
      also bitten by this tick showed symptoms of prurigo, fever and vomiting. Marine
      bird associated ticks bites may also be responsible for the inoculation of a
      number of arboviruses along all the coasts of the world including those of
      islands of Indian Ocean. Pathogenesis of the skin lesions is discussed according
      to the authors' histo-pathological findings.

PMID- 9642475
TI  - [No variation in chloroquine resistance (Plasmodium falciparum) from 1986 to 1996
      in semi-immune children in Brazzaville (Congo)].
AB  - A simplified Plasmodium falciparum in vivo test was carried out in Brazzaville
      (Congo) in April 1996. Chloroquine was prescribed at 25 mg/kg for 3 days in
      asymptomatic Brazzavillian school children who presented parasitemia > 800 P.
      falciparum trophozoites and lived in a highly endemic district. A massive
      decrease of parasitemia was observed on day 2. The percentage of resistance
      (presence of P. falciparum trophozoite on day 7 in a thick blood film) was 43.5,
      28 and 21 respectively (IC: 95%: 29-57, 15-41 & 10-34) at the threshold of 6, 50
      and 100 parasites/microliter. In positive children on day 7 the reduction of
      parasitemia was > 95% and no case of R3 resistance was detected. A comparison
      with previous studies carried out in 1985, 1986, 1990 and 1993 in the same school
      using the same methodology proves the long-lasting stabilization of chloroquino
      resistance for this semi-immune indigenous population.

PMID- 9642476
TI  - [Potability of drinking water sold in bags to public primary school children in
      Abidjan].
AB  - This study was carried out in order to determine the potability of drinking water
      sold in bags near 26 primary schools in Abidjan. Samples of this water revealed
      its poor microbiological and chemical quality. This exposes consumers to health
      risks. Consumers should be informed of the danger involved while vendors should
      be educated and their activities monitored by the Municipal Health services.

PMID- 9642477
TI  - [Intestinal parasites in the vendors and consumers of street food. A study
      conducted in the Dakar area].
AB  - In order to assess the parasitic risk for street-food consumers, the authors
      conducted two studies from September to August 1996, one on street-food sellers
      (305) and the other on consumers (235). Among the consumers, 127 were considered
      as not exposed to risk, since they did not frequent the sector being surveyed,
      and 108 were exposed because they consumed at least one meal per day cooked by
      the sellers of this area. Both groups filled out a questionnaire and had their
      stools analysed according to the RITCHIE method. The infection rate was 60% among
      sellers and 45.5% among consumers. Protozoans were predominant in both groups.
      Among the consumers, those exposed were significantly more infected. Even though
      the sellers represent a parasitic risk due to their level of infection and the
      typology of parasites they shelter, one cannot assume that consumers are
      contaminated only by the sellers of street food. However, appropriate measures
      must be implemented in order to minimize risks for street-food consumers.

PMID- 9642478
TI  - [Occurrence of onchocerciasis in subjects coming from non-endemic areas and
      migrating to a hyperendemic area].
AB  - The incidence of Onchocerca volvulus infection was measured from 1992-93 to 1995
      in six villages of initially uninfected migrants who settled in 1991 in the Vina
      Valley (Cameroon), an area of ongoing transmission of onchocerciasis. The mean
      annual incidence (MAI) exceeded 20% in the three communities located in the first
      line, and fewer than 15 km from the hyperendemic areas of the Central African
      Republic. The MAI was lower than 16% in the second line communities. As these
      populations are particularly at risk of developing ocular complications from
      onchocerciasis, it is recommended that repeated ivermectin distributions be
      organized in the migrant villages of the Vina Valley.

PMID- 9642479
TI  - [Is onchocerciasis endemic to Nyanza Lac (Burundi)?].
AB  - Several cases of onchocerciasis have been detected among suspected patients at
      the Nyanza Lac health centre, in southern Burundi. Surveys in three 'collines'
      (administrative units) of the commune of Nyanza Lac confirmed the presence of the
      disease (5.5% in the sample). However, all the onchocerciasis patients were
      adults and had immigrated from the near-by province of Bururi, where
      onchocerciasis is endemic. Furthermore, no aquatic forms of simuliid flies have
      been found in the prospected watercourses and the environment is not
      characteristic of an endemic region. Thus, one can conclude that onchocerciasis
      is imported, and not endemic, in the commune of Nyanza Lac, but that the
      proximity of other endemic areas could entail a risk of transmission.

PMID- 9642480
TI  - [Detection of hepatitis C virus in the general population of Tunisia].
AB  - We searched for antibodies to hepatitis C in a sample of 3079 Tunisians in the
      suburban area of Tunis. 30 people were positive by ELISA and 22 were confirmed by
      immunoblotting. This result represents a prevalence of 0.71% which is close to
      the values reported in European countries of the Mediterranean area.

PMID- 9642481
TI  - [Entomologic study on the transmission of onchocerciasis in a forest-savanna
      transition area of Cameroon].
AB  - An entomological study was conducted in the basin area of middle Sanaga
      (Cameroon) in order to document the pattern of onchocerciasis transmission in a
      region where a high prevalence of infection had been recorded in villages located
      30 km from the main rivers. The main vector of O. volvulus was found to be S.
      squamosum s.s. No breeding site was found in the small tributaries of the Sanaga
      and Mbam Rivers, and the dispersal of S. damnosum s.l. in the area thus appeared
      to be particularly high. The highest blackfly population densities were recorded
      during the long rainy season, and a second peak of density occurred along the
      Mbam River during the short rainy season. A seasonal variation in dispersal
      patterns was found at three of the four transects studied. The transmission of
      Onchocerca volvulus in the area occurred principally between January and May
      (i.e. at the end of the long dry season and the beginning of the short rainy
      season). Vector control operations might well reinforce the effect of ivermectin
      distributions in this onchocerciasis focus.

PMID- 9642482
TI  - [Anthropologic research and understanding pediatric visceral leishmaniasis in
      Tunisia].
AB  - In order to determine the social and cultural factors which delay hospitalization
      of children suffering from visceral leishmaniasis (VL), a study was carried out
      in the rural area of Kairouan (Tunisia). Qualitative techniques were used to
      investigate beliefs and behaviours associated with the symptoms of VL. The study
      has demonstrated that the folk interpretation of the disease interferes largely
      with the choice of the therapy. Regarding VL, the subdivision of the disease into
      two groups of symptoms, fever and splenomegaly, incites parents to consult
      doctors in the presence of fever and use traditional healers when splenomegaly
      appears. This is responsible for long delays before the patients can have access
      to official health care. This investigation clearly demonstrated that a health
      education programme is needed in VL endemic areas in Tunisia in order to shorten
      delays between the appearance of symptoms and their diagnosis. For this objective
      to be achieved, it would also seem necessary to implement simple serodiagnostic
      techniques at the periphery level.

PMID- 9642483
TI  - Optimum treatment of stable angina pectoris.
AB  - From a therapeutic point of view, angina pectoris is best thought of as an
      imbalance between oxygen supply and demand. Oxygen supply to the heart can be
      increased by improving endothelial function to increase vasodilation. Non
      endothelial-mediated vasodilation will also help increase coronary flow. Coronary
      vasodilators, such as the calcium blockers and nitrates, are effective agents in
      relieving vasoconstriction and improving coronary blood flow. Reduction of oxygen
      demand is accomplished by decreasing heart rate, blood pressure, heart size, and
      left ventricular mass. Beta-blockers and heart rate-lowering calcium entry
      blockers are effective in reducing oxygen demand. Additive effects occur by
      combining a beta-blocker and a dihydropyridine calcium entry blocker. Together
      with reduction of risk factors, this combination therapy plus aspirin provides
      optimal management of patients with angina pectoris.

PMID- 9642484
TI  - Proposed synergistic effect of calcium channel blockers with lipid-lowering
      therapy in retarding progression of coronary atherosclerosis.
AB  - Lipid-lowering therapy now has undoubtedly proven to be an effective therapeutic
      modality to retard the progression of coronary atherosclerosis. An additional
      approach for prevention of the progression of atherosclerosis is calcium channel
      blocker (CCB) treatment. Evidence indicating that CCBs inhibit atherosclerosis is
      less unequivocal than the clear evidence for lipid-lowering therapy. Many
      investigations support the view that a number of key processes in atherosclerosis
      may be influenced by CCBs. From the "negative" and "positive" studies with CCBs
      performed in animals and humans we must conclude that apparently some, but not
      all, types or stages of the atherosclerotic process are inhibited by CCBs. To
      assess whether lipid-lowering therapy and CCB treatment may have an additive or
      synergistic beneficial effect on human atherosclerosis, which is conceivable
      because their anti-atherosclerotic properties differ, data from the angiographic
      lipid-lowering trial REGRESS (pravastatin vs. placebo) were reviewed. In REGRESS,
      patients in the pravastatin group had significantly less progression if cotreated
      with CCBs as compared with those with no CCB cotreatment, whereas in the placebo
      (no pravastatin) group no effect of CCB treatment was observed. With respect to
      angiographic new lesion formation, in the pravastatin group there were 50% less
      patients with new angiographic lesions if cotreated with CCBs as compared with no
      CCB cotreatment, whereas in the placebo (no pravastatin) group, again, no
      significant effect of CCB treatment was observed. No beneficial effects of CCB
      treatment on clinical events were observed during the 2-year study follow-up. In
      view of the correlation between angiographic progression and subsequent clinical
      events as demonstrated in several large trials, it is not unrealistic to also
      anticipate in this population, a beneficial effect on clinical events with longer
      follow-up. Although the REGRESS trial was not designed to evaluate combination
      therapy, the results suggest that addition of CCBs to HMG-CoA reductase inhibitor
      therapy (pravastatin) acts synergistically in retarding the progression of
      established coronary atherosclerosis. These results appear to warrant prospective
      randomized trials to determine in a more definitive manner the merits of this
      combination in the prevention of progression of coronary atherosclerosis.
      Currently a number of studies in these fields are being designed or are already
      underway.

PMID- 9642485
TI  - Treatment of angina pectoris with calcium antagonists: long-term follow-up.
AB  - This study was designed to investigate the association of calcium channel blocker
      (CCB) use with subsequent mortality in a group of patients with chronic stable
      angina. CCBs have been proven effective in the treatment of angina pectoris.
      Recently, the safety of CCBs in hypertensive and coronary artery disease patients
      has been challenged. New prospective controlled studies with nifedipine are under
      way that may help define the long-term safety of CCBs in the treatment of these
      patients. Until these studies are concluded, long-term data on mortality among
      CCB users may be informative. From 1990 to 1992, 11,575 patients with coronary
      heart disease were screened but not included in a secondary prevention study with
      bezafibrate conducted in 18 cardiac departments in Israel. Of these patients,
      2390 had chronic angina without a history of myocardial infarction and were
      followed for subsequent mortality over 4-6 years (mean 5.2 years). From this
      patient population, 1366 (57%) reported receiving a CCB. They included more women
      and hypertensives, and a greater proportion of them exhibited a higher severity
      of anginal class than counterparts not treated with a CCB (n = 1024). The
      mortality in patients treated with CCBs was similar to those not treated with
      CCBs (11.5% vs. 11.6%; P = 0.53). A multivariate analysis accounting for
      differences in age, sex, and other clinical parameters associated with increased
      risk evaluated the estimated hazard ratio (HR) of death of patients treated with
      CCBs compared with those not treated with CCBs (HR = 0.89; 95% CI = 0.68-1.16).
      In Cox regression analysis, the adjusted HR of death of patients treated with
      nifedipine or diltiazem, together with a beta-blocker, was 0.85 (95% CI = 0.47
      1.54) and 0.47 (95% CI = 0.24-0.90), respectively. After a follow-up of 4-6 years
      (mean 5.2) there was no evidence of increased mortality risk associated with CCB
      use among coronary heart disease patients with chronic stable angina. However,
      due to wide confidence intervals and possible confounding factors, randomized
      control studies are required to provide definitive information.

PMID- 9642486
TI  - Endothelial function: strategies for early intervention.
AB  - Assessment of endothelial function appears to be a valuable additional tool for
      diagnosing and therapeutic monitoring of coronary artery disease. The first part
      of this review discusses the biosynthesis, degradation, and antiatherosclerotic
      properties of nitric oxide, a major determinant of endothelial function. In the
      second part methods for assessing endothelial function and strategies for
      reversal of endothelial dysfunction are reviewed. Improvement of endothelial
      function may be obtained by lifestyle modifications, such as cessation of
      smoking, better blood glucose regulation, exercise, dietary measures, and
      pharmacological interventions, such as lipid lowering, antioxidant therapy,
      angiotensin-converting enzyme inhibition, and calcium channel blockers.

PMID- 9642487
TI  - Effect of lipid-lowering therapy on myocardial ischemia.
AB  - Myocardial blood flow in patients with coronary artery disease depends on the
      severity of the coronary narrowings and the functional status of the coronary
      vessels. Coronary atherosclerotic plaques, which contain high concentrations of
      lipids, are more sensitive to change in coronary tone. The increased tendency of
      these active plaques for vasoconstriction is caused by abnormal endothelial
      function. Because regression of significant coronary plaques is highly unlikely,
      effort is made to improve endothelial function, thereby improving myocardial
      blood flow. Reduction of the cholesterol level by lipid-lowering drugs is
      associated with restoration of the vasodilatory response of the coronary
      arteries, thereby reducing the likelihood of plaque rupture and its consequences:
      myocardial infarction and death. Myocardial ischemia during daily life is induced
      by increased demand and increased coronary tone; therefore, it was not surprising
      that recent studies have indicated that cholesterol lowering reduced the
      frequency of daily ischemic episodes. Because improvement in endothelial function
      is already observed within a few weeks/months of lipid lowering, it is hoped that
      this therapy will rapidly reduce the frequency and severity of myocardial
      ischemia and its clinical expression, angina pectoris. At a later phase (1-2
      years), cholesterol lowering will also reduce major cardiac events.

PMID- 9642488
TI  - Cerebral dura mater and cephalalgia.

PMID- 9642489
TI  - Return to the headache in systemic lupus erythematosus using modern technology.

PMID- 9642490
TI  - Is cluster headache due to indolent inflammation in the cavernous sinus?

PMID- 9642491
TI  - Dopamine and migraine: a review of pharmacological, biochemical,
      neurophysiological, and therapeutic data.
AB  - The dopamine theory of migraine pathogenesis, first proposed by F. Sicuteri in
      1977, has attracted renewed interest after an increased frequency of the dopamine
      D2 receptor (DRD2) gene allele NcoI C was found in patients with migraine with
      aura. Therefore we reviewed the relevant literature. The most compelling argument
      favoring an interictal hypersensitivity of dopamine receptors in migraineurs
      stems from pharmacologic studies of the gastric and autonomic effects of
      dopaminergic agents such as apomorphine, but none of these studies was blinded
      and placebo-controlled. Various DRD2 antagonists abort migraine attacks after
      parenteral administration, while there is circumstantial evidence that dopamine
      agonists may be useful for prophylaxis. Most drugs used in these trials, however,
      lack selectivity for dopamine receptors. Both in pharmacological and therapeutic
      studies most patients had migraine without aura. We conclude that data suggesting
      a primary role for the dopaminergic system in migraine pathogenesis are
      unconvincing. Based on well established interactions between central amines, a
      reduced release of serotonin between attacks could lower dopamine release which
      would lead to receptor hypersensitivity.

PMID- 9642492
TI  - Cerebral dura mater and cephalalgia: relationships between mast cells and
      catecholaminergic nerve fibers in the rat.
AB  - The aim of the present study was to examine whether mast cells have the same
      variations as the related catecholaminergic nerve fibers. Chemical sympathectomy
      or surgical removal of right superior cervical ganglion induced a rapid decrease
      of fluorescence in both nerve fibers and mast cells, as confirmed by quantitative
      analysis (nerve fibers 19 +/- 1.1 vs 1.3 +/- 0.6; mast cell 10.8 +/- 1.9 vs 2.1
      +/- 0.3). The results of quantitative analysis after nerve fiber stimulation
      (electrical), however, showed an increase of the fluorescence in both the nerve
      fibers and the mast cells (nerve fibers 43.4 +/- 2.4; mast cells 18.6 +/- 1.6).
      Moreover, we found that the basal zone is more innervated (regarding
      catecholaminergic nerve fibers) than the apical one, and that the fluorescence
      level decreases passing from the vasal zone to the perivasal and intervasal
      zones. Further studies are needed in order to clarify the role of fluorescent
      nerve fibers and mast cells of cerebral dura mater in cephalalgia.

PMID- 9642494
TI  - Flow cytometric analysis of lymphocyte subsets in migraine patients during and
      outside of an acute headache attack.
AB  - We have conducted flow cytometric studies of two subsets of lymphocyte markers in
      groups of migraineurs during (n = 12; group B) and outside (n = 10; group C) of a
      migraine without aura attack (total n = 22; group A), including a group of
      patients tested in both of these phases (n = 5; group D), and compared these
      results with those obtained from a population of age-comparable, sex- and race
      matched healthy volunteers (n = 12; group E). Comparison of the first set of
      lymphocytes (CD3+CD16 + 56+, CD3-CD16 + 56+, CD3-CD19+, CD3+CD19+, and CD3+HLA -
      DR+) between the patients in group A and the controls (group E) showed
      differences, reflecting greater group A percentages of CD3+CD16 + CD56+ and CD3
      CD19+ lymphocytes. Furthermore, these differences reached statistical
      significance only for the CD3+CD16 + CD56+ lymphocytes, and then solely for the
      patients in group C (Scheffe's test, p < 0.05). Paired analysis of the above
      lymphocyte markers for subjects in group D failed to show significant differences
      between patients when they were having and not having a migraine attack, raising
      the possibility that results from a larger study could show meaningful increases
      in percentages of CD3+CD16 + CD56+ lymphocytes as one of the immune parameters
      useful for differentiating migraineurs from controls. Comparison of a second set
      of lymphocyte markers (CD19+CD5+, CD20+CD72-, CD20-CD72+, CD20+CD72+) among
      either the different groups of patients or between the patients and controls
      failed, however, to show statistically significant differences, emphasizing the
      apparent specificity of the findings described above for CD3+CD16 + CD56+
      lymphocytes. Our results, albeit of a preliminary nature, suggest the occurrence
      of significant, differential changes in lymphocyte subset immunophenotyping
      between groups of pain-free migraineurs and patients during an acute migraine
      episode or controls. Corroboration of these findings may prove useful in clinical
      laboratory practice to identify changes in immunological parameters specifically
      associated with migraineurs, and help towards a better understanding of the
      etiology and pathophysiology of this condition.

PMID- 9642493
TI  - A study of adaptive responses in cell signaling in migraine and cluster headache:
      correlations between headache type and changes in gene expression.
AB  - The project was an investigation into whether changes in the expression of G
      proteins underlie altered cell signaling in migraine and cluster headache. The
      basis for this assumption is that altered physiological responses are seen in
      migraineurs and that differences in cell signaling are detected biochemically in
      various cell types isolated from peripheral blood. Levels of three G-protein
      mRNAs--Gs alpha, Gi alpha, and Gq alpha, were quantified in lymphocytes from
      clinically well-defined migraine and cluster headache patients and correlated
      with headache type and influence of drug treatment. Gi alpha mRNA was reduced by
      50% in all migraine patients compared with control subjects; similarly in
      patients with or without aura, in patients with a migraine headache at the time
      of sampling, and patients in a quiescent state. No reduction in the levels of Gs
      alpha of Gq alpha mRNA were seen in migraine patients. A smaller reduction was
      seen in cluster headache patients, most marked in those without medication.
      Levels of Gs alpha mRNA were significantly reduced in cluster headache patients
      compared with migraine patients. The marked down-regulation of Gi alpha mRNA in
      migraine, whether quiescent or acute, indicates either an adaptive response to
      headache in this group of patients or that low levels of Gi alpha mRNA make
      individuals more susceptible to migraine.

PMID- 9642495
TI  - Age-related cerebrovascular disease alters the symptomatic course of migraine.
AB  - Migraine headaches usually decrease in frequency and severity and often cease
      during advancing age. Occasionally, migraineurs report late-life migrainous
      accompaniments, i.e., auras without headache, particularly when typical migraine
      attacks terminate or diminish following major or minor strokes, at which time the
      auras may become atypical. Clinical observations such as these suggest that
      degenerative cerebrovascular changes accompanying aging may modify the course of
      migraine headaches particularly those with aura. To test this hypothesis, we
      quantitated age-related changes in cerebral vasodilator capacitance by measuring
      local cerebral blood flow utilizing xenon contrast computed tomography (CT)
      scanning before and after oral administration of the pharmacological cerebral
      vasodilator, acetazolamide (Diamox). Measurements were compared among 27 normal
      volunteers without headache (aged 24-94 years; mean age 61.1 +/- 17.6) and 37
      carefully categorized groups of migraine patients (aged 27-83 years; mean age
      59.4 +/- 12.4). The normals comprised Group A. Migraineurs were divided into two
      subgroups: Group B consisted of 27 migraineurs with and without aura who
      continued to suffer from incapacitating and frequent headaches and Group C
      consisted of 10 migraineurs who no longer suffered from severe and frequent
      headaches, two of whom still complained of atypical auras of the "late-life
      migrainous accompaniments" type. Cerebral vasodilator capacitance significantly
      declined with advancing age among normals and the two groups of migraineurs,
      confirming the development of age-related cerebrovascular diseases. Global CBF
      increases after Diamox in Group B (with persistent and severe migraine), were
      significantly greater compared with normals without headache, and with Group C
      consisting of migraineurs whose headaches had decreased, subsided, or become
      replaced by late-life migrainous accompaniments (Group C). Results establish that
      cerebrovasodilator capacitance declines with advancing age, probably due to
      progressive cerebral atherosclerosis, since these declines were accentuated by
      risk factors for stroke, particularly TIAs or documented lacunar infarcts by CT.
      Progressive impairments of cerebral vasodilator capacitance among migraineurs
      were associated with: (i) reductions in frequency and severity of migrainous
      cephalalgia and (ii) appearance of late-life migrainous accompaniments.

PMID- 9642496
TI  - Structural and neurochemical markers of brain injury in the migraine diathesis of
      systemic lupus erythematosus.
AB  - OBJECTIVE: To determine whether migraine in systemic lupus erythematosus (SLE) is
      associated with accentuated brain injury and disease activity. METHODS: Forty SLE
      patients (11 without headache, 11 with non-migraine headache, and 18 with
      migraine) underwent clinical evaluation, magnetic resonance imaging (MRI), and
      spectroscopy (MRS). RESULTS: Recurrent headache occurred in 75% of SLE patients.
      MRI abnormalities and reduced N-acetylaspartate were common. However, migraine in
      SLE was not associated with increased disease activity or severity,
      neuropsychiatric manifestations, or end-organ involvement compared to patients
      without migraine (p > 0.05). There were no differences in the prevalence or
      severity of MRI or MRS abnormalities between SLE patients with migraine, with non
      migraine headache, or without headache (p > 0.05). CONCLUSIONS: Headache does not
      identify SLE patients at risk for brain injury, increased disease activity, or
      increased end-organ involvement. Aggressive immunosuppressive therapy for
      headache alone is not indicated in SLE.

PMID- 9642497
TI  - Peripheral autonomic potentials in primary headache and drug-induced headache.
AB  - Autonomic functions of different primary headache types have been investigated in
      several studies, most of them analyzing cardiovascular reflex mechanisms or
      biochemical changes. The results are contradictory; only in tension-type headache
      and in cluster headache has a sympathetic hypofunction been shown in a
      preponderance of studies. We analyzed the peripheral autonomous potentials (PAPs)
      in different primary headache types and in drug-induced headache and compared the
      results with those of healthy subjects and of patients with low back pain.
      Latencies of PAPs were significantly increased in all headache types but not in
      low back pain; amplitudes of PAPs did not show significant differences compared
      to healthy subjects. Patients with a long duration of drug abuse had increased
      PAP latencies, whereas patients with a high number of migraine attacks per year
      had decreased latencies. Our data suggest that sympathetic hypofunction as
      measured by PAP latencies is a general phenomenon in headache but not in all pain
      syndromes. Drug abuse leads to an increase of this hypofunction. While measuring
      PAPs is not an appropriate method by which to differentiate between headache
      disorders, it allows assessment of autonomic disturbances in primary and drug
      induced headache.

PMID- 9642498
TI  - Orbital pain as an isolated sign of internal carotid artery dissection. A
      diagnostic pitfall.
AB  - Head pain is one of the main presenting symptoms of internal carotid artery (ICA)
      dissection, usually in association with ischemic and/or local signs such as
      Horner's syndrome, lower cranial nerve palsies, or tinnitus. In rare cases, head
      pain remains isolated and mimics other conditions. We report a patient who
      suffered isolated prolonged orbital pain as the only sign of intrapetrous ICA
      dissection. Early recognition of such unusual facial pain may be crucial in
      decreasing the risk of secondary cerebral or retinal ischemia.

PMID- 9642499
TI  - Hypnic headache syndrome: a case with good response to indomethacin.
AB  - Hypnic headache syndrome is a rare benign disorder which occurs in the elderly.
      It presents as a holocephalic or, less frequently, hemicranial headache during
      night sleep, lasting between 20 and 180 min; it is not associated with autonomic
      signs and responds well to lithium carbonate. We report a new case which
      responded well to indomethacin, and suggest that indomethacin may be used as an
      alternative treatment in this rare headache syndrome of the elderly.

PMID- 9642500
TI  - Please don't hi-jack "quality of life".

PMID- 9642501
TI  - Hormone-related headaches.

PMID- 9642502
TI  - The transition G to A at position 20210 in the 3'-untranslated region of the
      prothrombin gene is not associated with migrainous infarction.

PMID- 9642503
TI  - Human cytomegalovirus: a viral complication in transplantation.

PMID- 9642504
TI  - Renal transplantation in secondary systemic amyloidosis.
AB  - When renal amyloidosis has progressed to end-stage renal failure, most patients
      are severely affected by systemic amyloidosis and nephropathy. An alternative to
      chronic dialysis is renal transplantation. We present a patient with amyloid
      nephropathy who developed recurrent transplant amyloidosis. Renal transplantation
      was performed in 1985 with a living related donor. In 1990 the patient developed
      amyloidosis of the graft with membranous nephropathy and tubular acidosis due to
      hyporeninemic hypoaldosteronism. Secondary amyloidosis has been reported to
      involve glandular organs inducing hypothyroidism, hypocortisolism and
      hypoaldosteronism. Cyclosporine has been reported to induce hyporeninemic
      hypoaldosteronism and tubular acidosis, but not hypocortisolism and
      hypothyroidism. Progression of the amyloidosis of the graft was confirmed by a
      renal biopsy in 1993. Data published in the literature indicate that the survival
      rate of amyloidotic graft recipients is worse than those of non-amyloidotic graft
      recipients. This was confirmed in an analysis of the current CTS data which
      showed an impaired survival rate at 5-yr of 66 +/- 4% (+/- SE) for patients with
      amyloidosis (n = 413) as compared with 86 +/- 1% (p < 0.0001) for patients with
      glomerulonephritis and 84 +/- 1 (p < 0.01) for patients with polycystic kidney
      disease. Graft survival after 5 years was 55 +/- 4% in patients with amyloidosis
      as compared with 63 +/- 1% (p = 0.02) in patients with glomerulonephritis and 68
      +/- 1% in patients with polycystic kidney disease. Graft survival was improved in
      amyloidotic patients treated with cylosporine as compared with patients on
      steroids and azathioprine (55 +/- 4% vs. 38 +/- 8%, p < 0.05). It is concluded
      that renal transplantation is the renal replacement therapy of choice for
      patients with AA-type amyloidosis although the overall patient survival is
      impaired in comparison with patients with other diseases.

PMID- 9642505
TI  - Use of a donor aortic cross for arterial reconstruction of the
      pancreaticoduodenal allograft.
AB  - Combined liver-pancreas procurement generally requires back bench reconstruction
      of the arterial blood supply with a donor Y-iliac graft to the pancreas graft. A
      modified vascular reconstruction that uses donor aortic cross including the
      brachiocephalic trunk and the left carotid artery as a single arterial patch is
      presented. This is useful when iliac grafts are unavailable or are being used as
      an alternative technique.

PMID- 9642506
TI  - Post kidney transplant quality of life prediction models.
AB  - Quality of life (QoL) is generally found to improve for renal transplant
      recipients, although some patients continue to experience health-related
      problems. It was within this context that we undertook our investigation which
      focused on identifying the factors predictive of QoL following kidney
      transplantation. METHODS: The sample included 91 non-diabetic patients of which
      69 provided 6-month data and 68 provided 12-month data. Three QoL questionnaires
      were administered to capture as many QoL dimensions as possible. Repeated measure
      analyses of variance with multiple post hoc comparisons of LS means was conducted
      to determine how QoL outcomes differed over time. Correlational analyses were
      performed on the 12-month dataset to determine which variables to include in the
      modeling process. Multiple stepwise regression with forward and backward entry
      were used in the prediction modeling. RESULTS: Essentially all patients
      experienced a significant improvement in QoL and the improvement occurred early
      and appeared to be sustained. Five separate prediction models were constructed,
      each including number of hospital days in first 6 months, employment, and social
      support. CONCLUSIONS: The similarity of the five models is of note. It is not
      necessarily these specific variables per se that predict QoL outcomes, but rather
      what they conceptually represent. These findings provide direction for
      interventions designed to enhance post-transplant QoL.

PMID- 9642507
TI  - Patterns of acute rejection in portal-enteric versus systemic-bladder pancreas
      kidney transplantation.
AB  - Portal-enteric (PE) transplantation of the pancreas allograft provides maintained
      physiologic drainage, and theoretically the portal delivery of transplantation
      antigens may have beneficial effects on the graft acceptance leading to improved
      graft survival. To determine whether the technique of pancreas placement affects
      the incidence of acute rejection we reviewed our experience in technically
      successful PE and systemic-bladder (SB) drained simultaneous pancreas and kidney
      (SPK) transplants performed between 1989 and 1994. Forty-seven recipients were
      included (SB = 30, PE = 17). All patients received cyclosporine based quadruple
      immunosuppression and survived at least 1 month. The two groups were comparable
      in HLA mismatches, cold ischemia time and level of immunosuppression at time of
      rejection. In the SB group the incidence of rejection was 1.04 kidney
      rejection/patient and 0.90 pancreas rejection/patient whereas the PE group
      experienced 0.53 kidney rejection/patient and 0.47 pancreas rejection/patient.
      The two groups were compared using incidence density statistics due to great
      variation in follow-up time. The SB group had a significant higher density of
      both kidney and pancreas rejections (p < or = 0.037 for kidney rejection and
      0.058 for pancreas rejection). In addition, while 6 of 30 (20%) pancreas grafts
      and 4 of 30 (13%) kidney grafts were lost to irreversible rejection in the SB
      group, only 1 of 17 (6%) pancreas graft and 1 of 17 (6%) kidney graft were lost
      in the PE group. These data demonstrate, that the PE placement of pancreas
      allograft affects the rates of acute rejection and graft loss, and imply that
      there exist some important immunological advantages when the pancreas graft is
      drained into the portal circulation.

PMID- 9642508
TI  - Usefulness of surveillance endomyocardial biopsy after pediatric cardiac
      transplantation.
AB  - Endomyocardial biopsy remains the 'gold standard' for the diagnosis of acute
      rejection after cardiac transplantation, but few guidelines exist to determine
      the indications for its use in pediatric cardiac transplant recipients. To
      determine the usefulness of surveillance endomyocardial biopsy, 176 biopsies were
      reviewed from 12 patients, aged 0.5-16 (average 9.7) yr, maintained on
      cyclosporine, azathioprine and prednisone immunosuppression, and followed 2.8
      45.5 (average 26.3) months after cardiac transplantation. Children old enough to
      cooperate (n = 6) underwent biopsy on nine occasions in the first 6 months after
      transplantation and quarterly thereafter. Children too young to cooperate (n = 6)
      underwent biopsy with general anesthesia on four occasions in the first 6 months
      after transplantation and every 6 months thereafter. Additional biopsies were
      performed as warranted by symptoms or noninvasive tests. A new episode of acute
      rejection was present in 13 biopsies (7%); continuing or resolving rejection in
      19 others (11%). Remaining biopsies had no evidence of rejection (82 biopsies,
      47%), had lymphocytic infiltrates insufficient for diagnosis (47 biopsies, 27%),
      were inadequate for diagnosis (14 biopsies, 8%), or were consistent with ischemia
      (1 biopsy, 0.5%). During the first 6 postoperative months, eight of 101 biopsies
      were positive for rejection, three occurring on routine surveillance biopsy.
      After 6 months, five of 75 biopsies showed a new episode of rejection, only one
      occurring on routine surveillance biopsy. Based on this data, it is concluded
      that: 1) episodes of rejection are relatively uncommon with triple drug
      immunosuppression; 2) surveillance biopsies in the first 6 months after cardiac
      transplantation may show unsuspected rejection; and 3) routine surveillance
      biopsies more than 6 months after cardiac transplantation are unlikely to show
      rejection in the absence of symptoms or other tests.

PMID- 9642509
TI  - Infection and associated risk factors in the immediate postoperative period of
      pediatric liver transplantation: a study of 176 transplants.
AB  - OBJECTIVE: To describe the characteristics of infections occurring in the
      immediate postoperative period of orthotopic liver transplantation (OLT) in
      children in a pediatric intensive care unit (PICU) and the associated risk
      factors. DESIGN: Retrospective cohort study. SETTING: Multidisciplinary 16-bed
      pediatric intensive care unit in a tertiary university hospital. PATIENTS: One
      hundred and thirty-three pediatric patients (range 6M to 22 yr) who underwent 176
      liver transplantations and were admitted to the pediatric intensive care unit for
      at least 48 h. RESULTS: A total of 180 infectious episodes (IE) occurred in 78
      (59%) patients who underwent 96 (54.5%) liver transplantations (1.35 IE/patient;
      1.02 IE/transplantation). The mean stay was 15.4 +/- 1.1 d (mean +/- SD) and 22
      patients died in the pediatric intensive care unit. One hundred and thirty-one IE
      (72.8%) were bacterial, 31 (17.2%) fungal, and 14 (7.8%) mixed bacterial and
      fungal. 39% of the IE appeared in the first postoperative week and 27% in the
      second postoperative week. The most common sites of infection were abdomen
      (48.3%) and blood stream (26.1%). Bacteria, alone or with fungi, were present in
      145 IE (1.1 IE/patient). Gram-positive aerobic bacteria (63%) predominated over
      gram-negative bacteria (54%) and fungi. Fungi were present in 45 IE; 53.4% of the
      infections occurred in lung (73% yeasts). The risk factors for infection that
      were identified were related with younger age, lower body weight, longer cold
      ischemia time, partial graft, and the volume of packed red blood cell
      transfusions. Infected patients had more postoperative complications and longer
      stay in the PICU (21 +/- 16 vs. 8 +/- 6 d), but no increase in mortality. The
      risk of infection increased 2.38 times with partial grafts and 1.1 times with
      each intraoperative transfusion of 20 ml/kg of packed red blood cells (RBC).
      CONCLUSIONS: Infection in the immediate postoperative period of pediatric OLT was
      related with a high morbidity but was not related significantly with increased
      mortality. The main risk factors for infection in the postoperative period of OLT
      were related essentially with small recipient size and the inherent complexity of
      the operation. Routine oropharyngeal decontamination is recommended, as well as
      early administration of oral nystatin in preoperative intestinal decontamination.
      The risk of infection increased 2.38 times with partial grafts and 1.1 times with
      the transfusion of every 20 ml of packed RBC.

PMID- 9642510
TI  - Incidence of leukopenia and cytomegalovirus disease in kidney transplants treated
      with mycophenolate mofetil combined with low cyclosporine and steroid doses.
AB  - Mycophenolate mofetil (MMF) combined with conventional cyclosporine and steroids
      doses efficiently prevents acute rejection in kidney transplants. However, this
      regimen has been associated with an increased incidence of cytomegalovirus (CMV)
      disease and leukopenia, specially in patients receiving MMF at 3 g/d, suggesting
      that the combination of two powerful immunosuppressants carries the risk of
      overimmunosuppression. For this reason, we treated a group of patients with MMF 3
      g/d combined with low cyclosporine and steroids doses. Eighty-two kidney
      transplants performed at two centers and enrolled in the European Mycophenolate
      Mofetil Cooperative Study were randomized to receive: A) placebo (n = 27); B) MMF
      2 g/d (n = 27); and C) MMF 3 g/d (n = 28). In this double blind study all
      patients received cyclosporine and steroids at conventional doses. Fifteen kidney
      transplants enrolled in an MMF open pharmacokinetic study were treated with MMF 3
      g/day combined with low cyclosporine and steroid doses (group D). Efficacy was
      evaluated as the incidence of biopsy proven acute rejection, and safety focused
      on CMV disease and leukopenia. Patients receiving MMF showed a low incidence of
      biopsy proven rejection (B) 18.5%; C) 10.7%; and D) 13.3%). Patients of group C
      had a high incidence of CMV disease (35.7%) when compared with the other groups
      (lower than 8%). Incidence of leukopenia was higher in patients treated with MMF
      (B) 25.9%; C) 39.3%; and D) 40%) than in placebo treated patients (7.4%).
      Patients in group (C) displayed leukopenia mainly in the context of CMV disease,
      while patients of group (D) had leukopenia not related to CMV infection. All
      patients of group (D) who presented leukopenia recovered after MMF reduction
      dose, while in group (C) there were 5 out of 28 patients who required MMF
      withdrawal. We propose that a reasonable approach to take advantage of a powerful
      non-nephrotoxic immunosuppressant such as MMF, could be the administration of
      this drug at 3 g/d from the time of transplantation combined with low CsA and
      steroid doses.

PMID- 9642511
TI  - Procalcitonin in the early phase after renal transplantation--will it add to
      diagnostic accuracy?
AB  - The determination of serum procalcitonin (PCT) was tested for its utility in
      detecting invasive bacterial infection and acute rejection during the first 6 wk
      after kidney transplantation. Fifty-seven kidney graft recipients were
      prospectively included in the study. In 13/57 patients, 16 episodes of acute
      biopsy-proven rejection occurred and were treated with high-dose steroids (n =
      14) or with OKT3 (n = 2). Seventeen out of 57 patients experienced 19 invasive
      bacterial infections; 2/57 had partial graft necrosis due to malperfusion. Twenty
      five out of 57 graft recipients experienced an uncomplicated postoperative
      course. A total of 116 samples were analyzed and the following data obtained:
      PCT, C-reactive protein (CRP), white blood cell (WBC) count, corresponding body
      temperature and serum creatinine. Procalcitonin values for patients with
      rejection did not differ significantly from those of the healthy transplant
      recipients (p = 0.47). In contrast, PCT was clearly elevated with invasive
      bacterial infection or partial graft necrosis (p < 0.01). OKT3 treatment of
      rejection led to a more than 10-fold increase in PCT. C-reactive protein, unlike
      PCT, was elevated to a variable extent in patients with graft rejection, though
      CRP values were significantly more elevated in patients with infection than in
      those with rejection (p < 0.01). The specifity for detection of invasive
      bacterial infection was 0.7 for PCT and 0.43 for CRP, whereas sensitivity was
      0.87 for PCT and 1.0 for CRP. There was no correlation between PCT and serum
      creatinine (r = 0.06). Haemodialysis did not lower PCT serum concentrations.
      Procalcitonin values rose postoperatively to peak levels on the first and second
      days and mostly declined to normals within 1 wk. In conclusion PCT, not being
      influenced by acute kidney graft rejection but serving as a specific indicator of
      systemic bacterial infection, could help to discriminate between both types of
      inflammation.

PMID- 9642512
TI  - Increased intragraft IL-15 mRNA expression after liver transplantation.
AB  - To study T-cell/macrophage interactions at the molecular level in clinical
      allograft rejection, we measured intragraft mRNA expression of the T-cell derived
      cytokine IL-2 and the macrophage derived chemokine IL-15, a novel cytokine
      associated with T-cell activation, in post-transplant liver biopsies (n = 33) and
      in non-transplanted control liver tissue by reverse transcriptase-polymerase
      chain reaction (RT-PCR). We analyzed biopsies without evidence of rejection (n =
      12), with spontaneously resolving histological rejection (n = 10), or with
      histological rejection accompanied with clinical rejection (n = 11) defined by
      rising serum bilirubin and aspartate amino transaminase levels. IL-15 mRNA
      expression was present in the majority of post-transplant liver biopsies (91%,
      30/33) and was significantly upregulated as compared with non-transplanted liver
      tissue (p = 0.005). However, the increased intragraft IL-15 mRNA level was not
      indicative for rejection. In contrast to intragraft IL-15 mRNA expression, IL-2
      mRNA transcription was measured in the minority of the post-transplant liver
      biopsies (15%, 5/33) and not detectable in control specimens. In addition, IL-2
      mRNA was almost specifically measured in rejection biopsies concurrent with graft
      dysfunction (36%, 4/11 versus 1/22 without clinical rejection; p = 0.03). No
      relation between intragraft IL-2 and IL-15 mRNA expression was found. The IL-15
      mRNA expression levels were not higher in the IL-2 negative rejections compared
      with those in IL-2 positive rejections. To conclude, in contrast to IL-2, the
      function of IL-15 in T-cell mediated rejection remains unclear. The overall high
      IL-15 mRNA levels in sites of immune responses suggests that the macrophage
      derived mediator IL-15 is involved in a constant flow of T-cells from the
      circulation into the graft.

PMID- 9642513
TI  - Apoptosis and hepatic allograft reperfusion injury.
AB  - Necrosis and apoptosis are distinct, but nonexclusive mechanisms of cell death.
      Until recently, investigators have focused upon necrosis as the sine qua non of
      lethal cell injury. Specifically, within the realm of liver transplantation,
      preservation strategies dealing with ischemia/reperfusion injury have
      concentrated upon minimizing the biochemical and histologic correlates associated
      with necrosis. Little is known of the role of apoptosis in reperfusion injury in
      human liver transplantation. Post-reperfusion liver biopsies from 35 patients
      were retrospectively analyzed for histologic evidence of necrosis. Apoptosis was
      identified histologically and using a chromogenic technique of in situ labeling
      of fragmented DNA. The number of apoptotic cells increased in parallel with the
      necrosis reperfusion score in a significant fashion (p = 0.003 by ANOVA). There
      was not a Zone 1, 2 or 3 predominance to the histologic distribution of apoptotic
      cells. The recipient peak serum transaminase values were also noted to increase
      with the reperfusion score (p = 0.001 by ANOVA). These results suggest that: 1)
      apoptosis occurs in the setting of reperfusion injury during human orthotopic
      liver transplantation (OLT); and 2) the extent of apoptosis increases in parallel
      with pathologic and biochemical parameters of reperfusion injury. Given the
      distinct nature of apoptosis and the highly regulated and conserved pathway for
      its initiation, inhibition of apoptosis with specific molecular targets, may
      serve to decrease allograft reperfusion injury.

PMID- 9642514
TI  - Serum lipase as a marker for pancreatic allograft rejection.
AB  - In patients with enteric drainage of pancreas transplants, urinary amylase cannot
      be used as a marker of rejection. Since most of the patients in our center have
      enteric drainage, the aim of this study was to evaluate serum lipase as a
      potential marker for rejection. From July 1994 to March 1997, 100 patients
      underwent pancreas transplantation with enteric (78) or bladder (22) drainage.
      Forty-two of the 100 patients had both daily serum lipase (sLip) values and
      either kidney core or fine needle aspiration biopsies of the pancreas and/or
      kidney. Thirty-one of the 42 had biopsy proven rejection and were treated on day
      0 (D0). From day -7 (D -7) to day +7 (D +7), sLip, serum amylase (sAmy), fasting
      blood sugar (FBS) and serum creatinine (sCr) were measured daily. Serum lipase
      values rose from 322 +/- 107 IU/L on D -2 to 634 +/- 247 IU/L on D -1 (p =
      0.0203) in 22 of the 31 patients with biopsy proven rejection (sensitivity 71%).
      The rise in sCr in combined kidney pancreas transplants with biopsy proven
      rejection was a better marker than sLip (sensitivity 86%). The sensitivity of
      sAmy and FBS was 50 and 33%, respectively. Other than sCr, sLip appeared to be
      the best marker for acute rejection in enterically drained pancreas transplants
      which should be useful as a non-invasive indicator of rejection in solitary
      pancreas transplants where sCr cannot be used.

PMID- 9642515
TI  - Orthotopic liver transplantation for hepatic associated metabolic disorders.
AB  - Hepatic associated metabolic disorders represent 5% of the indications for
      orthotopic liver transplantation (OLTX) according to the European Liver
      Transplant Registry. We studied the outcome of this group at our institution
      after OLTX and combined liver/kidney transplantation. Between September 1988 and
      January 1997, 837 OLTXs were performed in 735 patients. Patient survival and
      graft function at 1 yr were 91.3 and 86%, respectively. Thirty-nine OLTXs were
      performed in 38 patients (15 female/23 male, median age +/- SD: 35 +/- 14 yr,
      range 4-60 yr) due to liver associated metabolic disorders (4.7%). Indications
      included Wilson's disease (n = 14), alpha-1-anti-trypsin-deficiency (n = 7),
      hemochromatosis (n = 4), erythropoetic protoporphyria (n = 4), cystic fibrosis (n
      = 2), Crigler-Najjar syndrome type I (n = 1), glycogenosis type I (n = 1),
      ornithine-transcarbomylase-deficiency (n = 1). In addition 4 patients suffering
      from primary hyperoxaluria type I received combined liver/kidney grafts. Survival
      rate the 1 yr after OLTX and combined OLTX/NTX was 91.8%. Twenty patients
      received cyclosporin A (55%) and 17 patients tacrolimus (45%) as primary
      immunosuppression. The mean follow-up was 28.6 months (range 4-73 months). Two
      patients with hemochromatosis died 1 and 3 months after OLTX, respectively, from
      Aspergillus sepsis followed by multiorgan-failure. One patient died of malignant
      lymphoma 5 months after transplantation. One patient required retransplantation 2
      months after OLTX following arterial thrombosis and ischemic type biliary lesion.
      One year after OLTX, all patients demonstrated good graft function, liver grafts
      (ALT 17.9 +/- 13.6 IU/L, bilirubin 0.8 +/- 0.3.mg/dl, thromboplastin time 94 +/-
      15%), and combined liver/kidney grafts (creatinine 2.4 +/- 1.4 mg/dl). OLTX,
      respectively combined OLTX/NTX, represent a successful therapy for hepatic
      associated metabolic disorders. Survival rates and graft function are similar to
      those in liver graft recipients for established indications at our institution.
      OLTX seems to be an excellent treatment for hepatic based therapy resistant
      neurological disorders.

PMID- 9642516
TI  - Long-term quality of life after kidney and simultaneous pancreas-kidney
      transplantation.
AB  - We are using a validated questionnaire (SF-36) to annually assess health-related
      quality of life (QOL) in kidney and pancreas-kidney transplant recipients. The SF
      36 consists of eight scales to assess physical functioning, general health, and
      mental functioning. Norms and 95% confidence intervals (C.I.) have been developed
      for the US population. At present, 1138 recipients with functioning grafts (520
      Type I diabetic; 618 nondiabetic) 1-10 yr post-transplant have completed the
      questionnaire. Of the recipients, 446 completed the questionnaire once; 632
      twice; and 53 three times (305 after 1 yr; 266 after 2 yr; 256 after 3 yr; 206
      after 4 yr; 192 after 5 yr; 150 after 6 yr; 130 after 7 yr; 138 after 8 yr; 125
      after 9 yr; 92 after 10 yr). For both diabetic and nondiabetic recipients, there
      was little change in average scores for each scale between years (p = NS). In
      relation to the US population, average scores for nondiabetics were below the
      50th percentile on all 8 scales; for diabetics < 25th percentile on the physical
      functioning and vitality scales, < 50th percentile on all others. For both
      diabetic and nondiabetic recipients, average scores were higher than reported
      norms for patients with CHF, COPD, or depression but were similar to those with
      Htn or recent MI. Individual scores were then compared with age-matched means (+/
      2 SEMs) (95% C.I.) for the US population. At each year post-transplant, up to
      40% of nondiabetic and up to 65% of diabetic recipients had scores below the 95%
      C.I. on individual scales (particularly the physical functioning and general
      health scales)--e.g. over 30% nondiabetic and up to 60% diabetic recipients had
      scores on the physical functioning scales below the 95% C.I. More diabetic
      recipients (vs. nondiabetics) reported poor QOL on the physical functioning,
      general health and social functioning scales. There was little difference in the
      mental health scales. For those with Type I diabetes, a similar percentage of
      kidney and K/P recipients reported QOL below the 95% C.I. for the age-matched
      population, except on the GH scale (better QOL for K/P recipients). We conclude
      that successful transplant recipients report health-related QOL below that of the
      age-matched general population but similar to those with other chronic diseases.
      Diabetic and nondiabetic recipients have similar scores on the mental health
      scales; nondiabetic recipients score better on the general health and physical
      functioning scales.

PMID- 9642517
TI  - Two-hour cyclosporine level determination is the appropriate tool to monitor
      Neoral therapy.
AB  - To assess the safety profile of Neoral dose adjustment using cyclosporine (CsA)
      trough levels (C0) compared with levels obtained 2 h after the morning dose (C2),
      30 stable adult heart transplant patients 1 yr or more after surgery were
      converted from Sandimmune to Neoral. After a baseline visit (before conversion),
      initial follow-up included two visits (2 and 4-6 wk after conversion). After the
      first visit, patients were randomized to Group I (C0: 100-200 ng/ml) or Group II
      (C2: 200-400 ng/ml). Abbreviated pharmacokinetics were obtained for the
      estimation of the AUC0-4 h. Renal function was assessed by serum creatinine and
      the cimetidine-modified creatinine clearance. C2 correlated better than C0 with
      the AUC0-4 h (r = 0.91 vs. 0.63). Initial Neoral dose (mg/kg/d) was similar in
      both groups (2.8 +/- 0.5 and 2.8 +/- 0.8), and was lower in Group II at the
      second visit (2.0 +/- 0.7 vs. 3.0 +/- 0.6, p = 0.0001). C2 levels decreased in
      Group II from 912 +/- 438 to 555 +/- 271 ng/ml (p = 0.01), without evidence of
      acute rejection on endomyocardial biopsies. After the second visit,-both groups
      were monitored with C2, and the range was increased to 300-600 ng/ml. At the last
      visit (additional follow-up of 5 +/- 1 months), Neoral dose (mg/kg/d) was reduced
      to 2.0 +/- 0.3 in Group I (p < 0.001) and 1.8 +/- 0.4 in Group II. Serum
      creatinine was lower in Group II at the second visit (138 +/- 59 vs. 168 +/- 37
      mumol/L, p = 0.01) and was similar in both groups at the last visit. Neoral dose
      reduction based on C2 levels was not associated with acute rejection. The better
      correlation with the AUC0-4 h suggests that C2 may be more reliable than C0 for
      Neoral dose adjustment.

PMID- 9642518
TI  - Making sense of kidney transplantation: a view from African recipients.
AB  - This study investigated the experiences of African patients who have undergone a
      kidney transplant within the past 10 yr, either from a live donor or from a
      cadaver. Little is known about kidney transplantation among African patients, in
      particular about psychological and social responses to the process. The study
      examined how these patients made (and still make) sense of the transplant
      experience, and hence attribute a particular subjective meaning to the factors
      and variables which have been at play during the course of the transplant. Semi
      structured interviews were conducted with 14 African patients (8 women and 6
      men), from the Renal Unit of Groote Schuur Hospital, Cape Town. The interviewees
      were selected from the records of the Unit. Several themes accounted for the
      frameworks of meaning that patients attributed to the transplant process. These
      are: religion and indigenous belief systems; the role of the extended family;
      patients' respective routes to the hospital; feelings about the transplant; and
      experiences in the hospital.

PMID- 9642519
TI  - Effects of low-dose dopamine on urine output in oliguric, critically ill, renal
      transplant patients.
AB  - Low-dose dopamine (LD-DA) has been used extensively to increase urine output (UO)
      in critically ill patients. These effects have recently been documented in
      patients with normal and mildly abnormal renal function. The purpose of this
      study was to quantitate the effects of LD-DA on UO and urineNa (UNa) excretion in
      renal transplant (RT) patients, and thereby evaluate the effects of LD-DA on the
      denervated kidney. METHODS: Five RT patients and 7 non-transplant controls,
      hospitalized in the surgical intensive care unit (SICU), with serum creatinine
      (serum Cr) < 2 mg/dL who were oliguric (UO < 0.5 mL/kg/h), received LD-DA (2.5
      micrograms/kg/min). None received other diuretics within 12 h, and all had
      pulmonary artery occlusion pressure (PAOP) > 10 mmHg and CI > 3.0 L/min/m2. UO
      was measured hourly and averaged for 2 h pre and 6 h during LD-DA. All data are
      mean +/- SD. RESULTS: APACHE II (14 +/- 4), CI (4.1 +/- 1.2 L/min/m2), PAOP (15
      +/- 4 mmHg), HR (98 +/- 16/min), and MAP (83 +/- 10 mmHg) were similar between
      groups and did not change during LD-DA therapy. Initial serum Cr in the RT group
      (1.6 +/- 0.4 mg/dL) was greater than that in controls (0.9 +/- 0.24 mg/dL), p <
      0.05. Initial UO [0.26 +/- 0.10 mL/kg/h (RT) and 0.31 +/- 0.12 mL/kg/h
      (controls)] and initial UNa [8 +/- 62 meq/L (RT) and 54 +/- 28 meq/L (controls)]
      were not different. Urine output increased significantly compared with baseline
      in both groups [final UO 0.55 +/- 0.14 mL/kg/h (RT) and 0.96 +/- 0.41 mL/kg/h
      (controls)]. Final UNa [72 +/- 37 meq/L (RT) and 99 +/- 56 meq/L (controls)] were
      not different from each other or from baseline. CONCLUSIONS: LD-DA increases UO,
      but not UNa excretion, in RT patients with oliguria, comparably to controls.
      These data suggest that this effect is predominantly mediated by dopaminergic
      receptors, since the transplanted kidney is denervated and there were no
      significant associated changes in hemodynamic parameters during the study.

PMID- 9642520
TI  - Suggested guidelines for the use of tacrolimus in pancreas/kidney
      transplantation.
AB  - As experience with tacrolimus (FK506, Prograf) accumulates and reduced rejection
      rates are increasingly demonstrated, some transplant centers are adopting
      tacrolimus-based primary immunosuppressive regimens for their patients undergoing
      pancreas/kidney transplantation. The guidelines provided in this article based on
      the experience of four major US transplant centers, cover issues related to
      dosing, blood levels, concomitant use of mycophenolate mofetil (MMF), antifungal
      and antiviral prophylaxis, and drug interactions. For post-transplant
      immunosuppression some centers initiate oral tacrolimus administration on
      postoperative day 1, 2, or 3, while others wait until day 6 or 7, when renal or
      gastrointestinal function has resumed. Most centers endeavor to achieve higher
      target trough levels (approximately 10-20 ng/mL, but not higher) in the first 3
      months post-transplant, reducing levels thereafter. Several centers are now using
      MMF instead of azathioprine as an adjunct to tacrolimus. Conversion from
      cyclosporine to tacrolimus during maintenance therapy is often considered in the
      event of rejection or when adverse events do not respond to dosage reduction.

PMID- 9642521
TI  - Liver transplantation in hyponatremic patients with emphasis on central pontine
      myelinolysis.
AB  - Patients awaiting liver transplantation may suffer from severe hyponatremia. It
      has been suggested that hyponatremia or its treatment might be associated with
      central pontine myelinolysis (CPM), a serious complication that can be seen after
      orthotopic liver transplantation (OLT). We undertook this study to assess the
      outcome of hyponatremic patients after OLT and to evaluate the risk factors in
      the development of CPM. A total of 379 adult OLT performed in 347 patients
      between March 1993 and December 1995 was studied using a prospectively-collected
      data base and retrospective chart review. The following risk factors for the
      development of CPM were analyzed: primary liver disease, nutritional status,
      alcoholism, diuretic use, hepatic encephalopathy, United Network for Organ
      Sharing (UNOS) status, preoperative serum sodium, magnesium and cholesterol
      levels, increase in serum sodium concentration during surgery, and
      immunosuppressive treatment. Overall 12 patients (3.5%) underwent OLT in a
      hyponatremic state (serum sodium < or = 127 meq/L). At a median follow-up of 14
      months, 8 patients were alive without any neurological sequel. Six of the 12
      patients developed neurological complications in the early post-operative period
      including CPM in 3, confusion in 2, and seizure in 1. The 3 patients who
      developed CPM expired within 3 months of OLT. The changes in serum sodium
      concentration during OLT in patients with and without CPM were 20.7 +/- 8.1 and
      7.0 +/- 5.1 meq/L, respectively (p = 0.005). No other risk factor could be
      identified in the development of CPM. It is concluded that prognosis of
      hyponatremic patients after OLT is poor if they develop CPM. Slow correction of
      hyponatremia perioperatively may be critical in preventing this devastating
      complication.

PMID- 9642522
TI  - Maintenance therapy with oral ganciclovir after treatment of cytomegalovirus
      infection.
AB  - While oral ganciclovir (OGCV) has been used as primary prophylaxis in patients at
      high risk for cytomegalovirus (CMV) infection after solid organ transplantation,
      its value in secondary prophylaxis is unknown. We have examined the use of OGCV
      as maintenance therapy following confirmed CMV infection on 16 occasions in 15
      patients, in kidney (n = 4), kidney-pancreas (n = 3) lung (n = 6) and heart-lung
      (n = 1) recipients. OGCV was used in two distinct clinical situations. One group
      (n = 7) received OGCV as consolidation therapy (mean duration of 21 +/- 5 d)
      following i.v. ganciclovir induction therapy (mean duration of 16 +/- 5 d) for
      acute CMV infection, and sustained remission was achieved in 6/7 patients for a
      median follow-up of 300 d. In the second scenario, OGCV suppressed clinical
      disease in all patients with relapsing CMV infection (n = 9), with minimal or
      absent toxicity with a median follow-up of 152 d. OGCV reduced morbidity by
      allowing removal of central lines used for long-term i.v. therapy in patients
      with poor peripheral access. Hence, this study demonstrates the safe and
      effective use of OGCV as consolidation therapy after standard induction treatment
      with i.v. ganciclovir, and as long-term suppressive therapy in transplant
      recipients with recurrent CMV infection.

PMID- 9642523
TI  - Disseminated histoplasmosis in a patient after orthotopic liver transplantation.

PMID- 9642524
TI  - Acute acalculous cholecystitis (AAC) resulting in gallbladder perforation in a
      solid organ transplant recipient: a case report.
AB  - Gallbladder perforation is a frequent complication of acute acalculous
      cholecystitis (AAC), resulting in substantially increased morbidity and
      mortality. Two groups of patients are at increased risk for perforation: those
      with systemic diseases (especially peripheral vascular disease, intrinsic heart
      disease, or diabetes) and those who are chronically immunosuppressed. The current
      population of solid organ transplant recipients meets both criteria. We describe
      an unusual case of gallbladder perforation as a complication of AAC in an
      otherwise healthy kidney transplant recipient. Because transplant recipients are
      at increased risk for gallbladder perforation, maintaining a high index of
      suspicion for this complication will help avoid the increased morbidity and
      mortality associated with this diagnosis.

PMID- 9642526
TI  - History of iatrogenic disease.

PMID- 9642525
TI  - A liver with polycystic liver disease as graft for orthotopic liver
      transplantation.
AB  - Donor organ shortage calls for widening of criteria for organ transplantation. In
      exceptional cases, even livers with macroscopic alterations may be accepted for
      transplantation. The case of a patient who received a liver graft from a donor
      with previously unknown adult polycystic degeneration is reported. The liver
      showed only small bilobar cysts with less than 10% of hepatic replacement and was
      successfully used for orthotopic liver transplantation. Two years after
      transplantation the patient is in good clinical condition and has returned to
      work.

PMID- 9642527
TI  - Drug-induced lichen planus.

PMID- 9642528
TI  - Drugs in exacerbation and provocation of psoriasis.

PMID- 9642529
TI  - Drug-induced scleroderma and sclerodermiform conditions.

PMID- 9642530
TI  - Drug-induced lupus erythematosus.

PMID- 9642531
TI  - Drug-induced pemphigoid: bullous and cicatricial.

PMID- 9642532
TI  - Drug-induced linear immunoglobulin-A bullous dermatosis.

PMID- 9642533
TI  - Drug-induced pemphigus.

PMID- 9642534
TI  - Drug-induced toxic epidermal necrolysis.

PMID- 9642535
TI  - Current opinions in headache pathogenesis: introduction and synthesis.

PMID- 9642536
TI  - Cluster headache: imaging and other developments.
AB  - Cluster headache, one of the most severe pain syndromes in humans, is usually
      described as a vascular headache. However, the striking circadian rhythmicity of
      this strictly unilateral pain syndrome cannot readily be explained by the
      vascular hypothesis. Recent studies using positron emission tomography suggest
      that a central nervous system dysfunction in the region of the hypothalamus is
      the primum movens in the pathophysiology of cluster headache. From a
      physiological viewpoint, therefore, cluster headache should be described as a
      neurovascular headache, thus placing equal emphasis on its fundamental
      pathophysiology and clinical expression.

PMID- 9642537
TI  - Brain excitability in migraine: evidence from transcranial magnetic stimulation
      studies.
AB  - Central neuronal hyperexcitability is proposed to be the putative basis for the
      physiologic disturbances in migraine. Because there are no structural
      disturbances in migraine, only physiologic studies can provide insight into the
      underlying mechanisms. Recently, transcranial magnetic stimulation has been
      developed as a valuable research tool and can be used to study brain function
      noninvasively. This article is a review of the studies done in migraine using
      transcranial magnetic stimulation.

PMID- 9642538
TI  - Current status of genetic discoveries in migraine: familial hemiplegic migraine
      and beyond.
AB  - Familial hemiplegic migraine (FHM) has been related to mutations in a brain
      calcium channel gene among Chr19p linked FHM families. Subsequent genetic Studies
      in different FHM families showed that additional causative genes must reside in
      other regions of the genome, including the long arm of Chromosome 1. Parallel
      discoveries in mouse mutants involving ion channel genes have also accelerated
      our understanding of the spectrum and functional significance of the CNS-related
      ion channel disorders. These studies have clear implications for migraine,
      epilepsy, and ataxia. An association study was suggested that other
      'susceptibility' genes like the dopamine DRD2 receptor will be important in
      characterizing the genetic components of the larger, heterogeneous group of
      migraine disorders.

PMID- 9642539
TI  - The place of migraine as a channelopathy.
AB  - Over the past 8 years an increasing awareness of the role of mutant ion channels
      in episodic diseases of humans has emerged. The importance of these discoveries
      is now being extended to a growing list of membrane excitability disorders of the
      nervous system. Molecular characterization of episodic diseases that are rare and
      monogenic will ultimately shed light on more common and complex disorders, such
      as epilepsy and migraine.

PMID- 9642540
TI  - Recent advances in mechanisms of spreading depression.
AB  - Although spreading depression has been known for over 50 years, recent research
      into this interesting experimental phenomenon provides evidence for an
      integrative role of spreading depression in brain pathophysiology. Spreading
      depression activates neurophysiological pathways that may have widespread
      consequences on brain function, but depends on the basal energy state of the
      brain.

PMID- 9642541
TI  - Inflammatory myopathy in myasthenia gravis.

PMID- 9642542
TI  - Chronic inflammatory diseases of the nervous system.
AB  - In many neurologic diseases, activated leukocytes enter the nervous system and
      initiate a chronic inflammatory process. Understanding how the cellular and
      humoral responses are associated with pathogenesis is essential for the
      formulation of a unifying model of central and peripheral nervous system
      inflammation. Based on such a model, immunotherapeutic strategies and protocols
      can be designed.

PMID- 9642543
TI  - Central nervous system vasculitis.
AB  - Central nervous system vasculitis occurs in a variety of clinical settings. Some
      exhibit a distinct age preference; others a tissue tropism. Most frequently
      encountered are giant cell arteritis (temporal arteritis) and vasculitis
      secondary to infections. The central nervous system may be involved in the
      antineutrophil cytoplasmic antibody-associated systemic vasculitides and
      occasionally neurologic abnormalities appear as a presenting manifestation of
      disease. Isolated angiitis of the central nervous system, a rare form of
      vasculitis that is restricted to the central nervous system, must be
      distinguished from other causes of central nervous system inflammation and from
      noninflammatory vascular disease. We are learning a great deal about the cellular
      mechanisms of vascular inflammation in general. Some manifestations of the
      clinical disease result from histologic features of the infiltrate and the size
      of affected vessel. However, the local consequences of inflammation, such as
      increased coagulation and altered vasomotor tone, as well as the systemic
      consequences, such as activation of the central noradrenergic systems,
      trigeminovascular system, and hypothalamic pituitary adrenal axis, contribute
      both to pathogenesis of disease and to recovery.

PMID- 9642544
TI  - Neurological involvement in systemic lupus erythematosus.
AB  - The aetiology of neurological involvement in systemic lupus erythematosus (SLE)
      still remains largely uncertain, but there are some recent reports of retrovirus
      activity linked to human and mouse models of SLE. Antiribosomal P antibodies
      appear specific to SLE and tend to be associated with psychiatric disease, but
      not exclusively so. The role of antiphospholipid antibodies in the pathogenesis
      of SLE may not be solely to cause thrombotic events, but also to act directly on
      neuronal tissue. The importance of another group of antibodies, those against
      Beta 2 glycoprotein I, a phospholipid binding protein, is now being recognized.
      Amongst the many neurological manifestations of SLE, cognitive impairment is
      becoming increasingly recognized and appears not to be simply a response to
      chronic disease or its treatment. Of the newer imaging techniques applied to SLE,
      positron emission tomography has proved inconsistent and somewhat disappointing
      but single photon emission computed tomography in active disease appears more
      sensitive compared to MRI, although it still remains a nonspecific technique. The
      treatment of SLE remains disappointing and no controlled trials for neurological
      disease have been published to date but a number of experimental approaches do
      offer hope for the future.

PMID- 9642545
TI  - Lyme neuroborreliosis.
AB  - A broad variability in the clinical manifestations is observed in the European
      and North American borrelioses. This is dependent on bacterial strain differences
      in virulence and organotropism, and on different immune responses to Borrelia
      burgdorferi of the host in these areas. Experimental neuroborreliosis has given
      insights into mediators and molecular mechanisms of inflammation induced by B.
      burgdorferi. Histopathological investigations have described the different
      patterns of injury in the peripheral and central nervous systems. The classic
      symptoms of neuroborreliosis have been supplemented by new clinical syndromes and
      neuropsychological investigations. In clinical trials, the efficacy and cost
      effectiveness of recommended oral and intravenous antibiotic therapies have been
      compared in early Lyme disease, arthritis and acute disseminated Lyme disease.

PMID- 9642547
TI  - Headache.

PMID- 9642548
TI  - Inflammatory diseases.

PMID- 9642546
TI  - New variant Creutzfeldt-Jakob disease.
AB  - New variant Creutzfeldt-Jakob disease is a novel human prion disorder with
      characteristic clinical and neuropathological features, which results from
      exposure to the bovine spongiform encephalopathy agent. The probably lengthy
      incubation period makes it difficult to predict future new variant Creutzfeldt
      Jakob disease case numbers; further studies are required to clarify risk factors
      and the potential for human spread.

PMID- 9642549
TI  - Age degradation in top-down processing: identifying objects from canonical and
      noncanonical viewpoints.
AB  - Twenty-four young (mean age 21.8 years) and 24 old (mean age 65.2 years)
      participants were asked to determine whether spoken words correctly named
      pictures of objects. Half of the objects were portrayed from noncanonical
      (unusual) viewpoints, and half were portrayed from canonical viewpoints. The
      older participants required more time and made more errors when they evaluated
      the noncanonical pictures (relative to the canonical pictures) than the younger
      participants. This finding is consistent with previous evidence that frontal lobe
      function degrades with aging and with results from a positron emission tomography
      study (S. M. Kosslyn et al., 1994) that showed that the frontal lobes (among
      other areas) are activated more in the noncanonical condition than in the
      canonical condition.

PMID- 9642550
TI  - The relationship of cortisol to practice-related gains in intelligence among
      older persons.
AB  - Based on data collected from two separate samples of older adults, the present
      study explored the role of cortisol in mediating practice-related gains in fluid
      intelligence (Gf) among older adults. Analyses across samples involved treatment
      group participants who received stress inoculation training in order to reduce
      anxiety concerning intellectual performance; waiting list control group
      participants did not receive training until the experiment(s) were completed.
      Practice effects were examined for both groups. In Study 1, the sample consisted
      of a heterogeneous (re: concerns about intellectual performance) group of older
      adults, and Study 2 participants were older adults who self-reported as being at
      least moderately anxious or concerned about intellectual performance declines.
      The two samples differed on health (p < .01), with Study 2 participants being
      healthier (as determined via self-report). Results indicated that practice, but
      not training, effects were evident for measures of crystallized ability (Gc) and
      Gf across both studies. The data also suggested that cortisol mediation was
      different for the two samples in that it was negatively correlated with Gf in the
      first sample, and, though not significant, positively correlated with Gf in the
      second. The same directional relationships were evident for the measure of Gc.
      Comparisons between studies regarding correlations between cortisol and practice
      related gains in performance were significant for Gf (p < .01) and approached
      significance for Gc (p < .07). These data seem to suggest that for some older
      persons, higher levels of cortisol interfere with the effects of practice on Gf
      performance, while for others, higher cortisol facilitates such gains in
      performance.

PMID- 9642551
TI  - The influence of list format and category headers on age differences in
      understanding medication instructions.
AB  - We examined whether instructions are better understood and remembered when they
      contain organizational cues. Our previous research found that older and younger
      adults organize medication information in similar ways, suggesting that they have
      a schema for taking medication. In the present study, list formats (vs.
      paragraphs) emphasized the order of information and category headers emphasized
      the grouping of information specified by this schema. Experiment 1 examined
      whether list and header cues improve comprehension (answer time and accuracy) and
      recall for adults varying in age and working memory capacity (measured by a
      sentence span task). List instructions were better understood and recalled than
      paragraphs, and reduced age differences in answer time and span differences in
      accuracy. Headers reduced paragraph comprehension for participants with lower
      levels of working memory capacity, presumably because they were not salient cues
      in the paragraphs. Experiment 2 investigated if headers were more effective when
      more saliently placed in paragraphs and lists, and if list and header cues helped
      readers draw inferences from the instructions. List formats again reduced age
      differences in comprehension, especially reducing the time needed to draw
      inferences about the medication. While headers did not impair comprehension,
      these cues did impair recall. The present study suggests that list-organized
      instructions provide an environmental support that improves both older and
      younger adult comprehension and recall of medication information.

PMID- 9642552
TI  - Visual and Haptic influences on memory: age differences in recall.
AB  - Older (age 60-75) and younger adults (age 20-35) participated in a within-subject
      experiment. All participants were given four lists of 17 items, a recall test
      followed each list. Each participant was given a separate list under each of the
      following conditions, at the rate of 1 item every 10 s. (1) control: list of
      nouns; (2) visual-only: visually shown objects; (3) visual-and-haptic: given
      objects to hold and visually examine; (4) haptic-only: blindfolded, given objects
      to hold. A final surprise recall test was given of all items presented in the
      study. Data indicated that younger adults recalled more than older adults under
      all conditions. However, both age groups had the highest recall under the haptic
      conditions.

PMID- 9642553
TI  - The effect of age on the learning of a nondeclarative category classification
      task.
AB  - A category classification task was administered to participants in their twenties
      through their eighties. Participants studied a set of high distortions of a
      prototype dot pattern and were then asked to choose whether or not a new set of
      dot patterns (random patterns, high distortions, low distortions, and the
      prototype) belonged to the same category of dot patterns as studied. Participants
      were also administered a recognition test after studying a second set of dot
      patterns. There were no significant differences for age groups on the pattern
      recognition test. In 2 of the 3 analyses of the category classification task,
      there were no significant age effects. However, there was a small age effect in
      one analysis with the young making more accurate classifications on two aspects
      of the task. The results are consistent with the view that small age-related
      effects may exist for some tests of nondeclarative memory.

PMID- 9642554
TI  - The influence of aging and target motion on the control of prehension.
AB  - The purpose of this study was to examine age-related differences in reaching
      behavior when younger (mean age = 26.0 years) and older (mean age = 70.1 years)
      individuals were required to reach toward and grasp both small and large targets
      that were either stationary or moving. The older subjects had shorter movement
      times, and smaller within-subject movement time variability than younger
      subjects. Also, the deceleration of the reach was shorter for older subjects,
      indicating that they were not making extensive use of on-line feedback, and were
      instead utilizing anticipatory control strategies. There were no age differences
      in the size of the maximum grasp around the target, but the timing of the grasp
      was influenced by target motion for the younger subjects, suggesting on-line
      control for the younger subjects only.

PMID- 9642555
TI  - [Tumescence local anesthesia. Improvement of local anesthesia methods for
      surgical dermatology].
AB  - The tumescent technique of local anesthesia was developed by J. Klein ten years
      ago to facilitate liposuction surgery. Tumescent anesthesia not only became the
      standard technique for liposuction, but proved to be of great value for other
      surgical problems in dermatology. Meanwhile, several noncosmetic uses for
      tumescent anesthesia were pioneered by dermatologic surgeons. This first review
      of the tumescent technique in German literature will focus on its specific
      advantages and disadvantages when applied in different fields of dermatologic
      surgery. Our own experience will be discussed, as well as future developments.

PMID- 9642556
TI  - [Coincidence of scleroderma and primary biliary cirrhosis. Results of a
      systematic study of a dermatologic patient sample].
AB  - We present for the first time in the German dermatologic literature results of
      systematic investigations on the relationship between scleroderma,
      antimitochondrial autoantibodies and primary biliary cirrhosis (PBC). 40 patients
      with different clinical pictures of systemic and localized scleroderma were
      examined. By means of indirect immunofluorescence technique, in the sera of 5
      cases (12.5%) antimitochondrial autoantibodies (AMA) could be detected. The
      target autoantigens for the AMA were identified as pyruvate dehydrogenase,
      branched-chain alpha-ketoacid dehydrogenase, alpha-ketoglutarate dehydrogenase,
      protein x and pyruvate dehydrogenase E-1 alpha in all 5 cases, PBC was confirmed
      by means a liver biopsy and endoscopic retrograde cholangioscopy. Considering the
      occurrence in the normal population, the prevalence of the PBC in our scleroderma
      collective was 8.3 x 10(2) to 2.5 x 10(3) x higher. In respect to the clinical
      picture of the scleroderma, we found a M2-antibody-positive PBC in 2 woman with
      CREST syndrome and in 1 woman with a acral-type of the progressive systemic
      scleroderma. CREST syndrome and coexistently M2-antibodies in the serum are a
      risk constellation for the development of PBC. In 2 female patients older than 50
      years we observed the coincidence of disseminated plaque-like localized
      scleroderma and a M2-antibody-positive PBC. In our opinion this latter
      constellation is a specific entity. The administration of ursodeoxycholic acid
      (daily 15 mg/kg BW) in 3 cases led not only to dramatic improvement of the
      clinical symptoms of PBC as expected, but also to pronounced improvement of skin
      lesions of 2 patients with disseminated circumscribed and 1 patient with
      progressive systemic sclerosis. Thus PBC should be searched for in patients with
      scleroderma, especially those with CREST syndrome or widespread localized
      disease; it may have practical therapeutic value as well as immunological
      significance.

PMID- 9642557
TI  - [Laser skin resurfacing. Er:YAG laser and cw-CO2 laser with scanner system in
      direct comparison].
AB  - We compared a cw carbon dioxide flash-scanning laser system to an Er:YAG laser in
      laser skin resurfacing of facial rhytides. In all patients, CO2 laser treatment
      showed a better cosmetic result whereas erythema and postinflammatory
      hyperpigmentation were less marked in Er:YAG laser therapy.

PMID- 9642558
TI  - [Quality of life in chronic venous insufficiency (CVI). Results of a study with
      the newly developed Tubingen Questionnaire for measuring quality of life of
      patients with chronic venous insufficiency].
AB  - Across the boundaries of the medical specialties we have realized how important
      the concepts of quality of life and disease-related coping behavior are to
      understand the patients' subjective perception of the medical condition and its
      treatment. Although standardized instruments are already available for different
      medical indications and even in the related fields of peripheral vascular and
      cardiac diseases, phlebology still lacks standardized concepts for evaluating
      quality of life and/or disease-related coping behavior in patients with chronic
      venous insufficiency (CVI). We report on a newly developed instrument
      specifically designed for recording quality of life in patients with CVI. It not
      only meets the requirements of psychometric standards, but has also proven its
      applicability in clinical use. The "Tubingen Questionnaire for measuring Quality
      of Life in patients with CVI (TLQ-CVI)" and the results of a study on quality of
      life in 142 patients with various stages of chronic venous insufficiency are
      presented. It was possible to distinguish between Stage I/II and Stage III CVI
      patients with respect to parameters such as "leg complaints" and "day-to-day
      fears and worries". These convey clinically relevant insights into the patient's
      subjective perception of the disease and how they cope. The information gathered
      provides a set of reasonable target scores for clinical studies presently being
      carried out at various study centers in Germany incorporating the TLQ-CVI.

PMID- 9642559
TI  - [Incidence of gynecomastia in dermatology patients].
AB  - Gynecomastia is an enlargement of the male breast. We studied a group of 115 men
      attending a dermatological clinic to evaluate the frequency of possible risk
      factors and hormonal findings. Gynecomastia was diagnosed, if a horizontal
      skinfold exceeded 2-3 cm, and if the diameter of the areola wa greater than 3 cm.
      In 32 patients (27.8%) the criteria for gynecomastia were fulfilled. The
      frequency increased significantly with the body mass index. 18 different
      medications were identified, but only two were take by more than two patients
      (allopurinol, coronary dilators). None of the 15 underlying diseases was
      associated with a significant increase or decrease in the risk of gynecomastia.
      Serum cortisol was the only endocrine study which was associated with an
      increased incidence of gynecomastia. As gynecomastia appears frequently as a
      phenomenon unrelated to other diseases or medications, it may be a condition per
      se.

PMID- 9642560
TI  - [Lichen planopilaris simulating postmenopausal frontal fibrosing alopecia
      (Kossard)].
AB  - A 68-year old woman presented with a frontal fibrosing alopecia and lesions of
      the buccal mucous membranes typical for lichen planus. Postmenopausal frontal
      fibrosing alopecia (PFFA) has recently been described by Kossard as a distinct
      entity characterized by progressive recession of the frontotemporal and parietal
      hair margins leading to permanent alopecia in the form of a symmetrical band-like
      area of scanning in postmenopausal women. The histology (perifollicular
      lymphocytic infiltration and fibrosis, increase of apoptosis of hair follicle
      keratinocytes) is indistinguishable from that of lichen planopilaris. The
      localization and age- and sex-related characteristics of PFFA are not sufficient
      to delineate it as a discrete entity from lichen planopilaris. Our observation of
      oral lichen planus in a postmenopausal woman with frontal fibrosing alopecia
      points to the possibility that PFFA actually may represent a variant of lichen
      planopilaris with a predilection for the frontotemporal hairline. Other variants
      of lichen planopilaris include multifocal lichen planopilaris, disseminated
      lichen planopilaris (Lassueur-Graham-Little syndrome), lichenoid pseudopelade,
      and any combination of these ("mixed type"). An effective therapy of PFFA is not
      known. Also, treatment of lichen planopilaris forms in which fibrosis
      predominates over inflammation is similarly problematic, but the natural course
      of these diseases seems to be self-limited.

PMID- 9642561
TI  - [Cutaneous sinus histiocytosis (Rosai-Dorfman disease)].
AB  - Sinus histiocytosis is as a rule a benign disease of lymph nodes, infiltrated by
      large histiocytes. These cells show typical cytophagocytosis, particularly
      lymphophagocytosis. Other organs may be also involved by this disease, often
      including the skin. Exclusive cutaneous sinus histiocytosis without infiltration
      of lymph nodes seems to be very rare. To exclude other non-X histiocytoses or
      histiocytosis-X, it is advisable to use immunohistochemistry. We report on a
      patient with sinus histiocytosis and discuss the problems of differential
      diagnosis.

PMID- 9642562
TI  - [Tinea caused by Trichophyton equinum].
AB  - We report on the first human infection with Trichophyton equinum in Germany,
      which was transmitted from an infected pony to a 12-year old girl. Trichophyton
      equinum was identified by its morphology, dependency on nicotinic acid, hair
      perforation, and enzyme production. A noteworthy new observation was the
      development of white pleomorphic tufts on the surface of thalli grown on potatoe
      dextrose agar. The girl's tinea was non-inflammatory and responded promptly to
      topical treatment, whereas the pony's strongly inflammatory lesions persisted for
      months. In supernatants of cultures supplemented with different nutrients, enzyme
      patterns were measured for Trichophyton equinum that correspond to other species
      of dermatophytes more pathogenic for humans. Therefore, a lack of enzymes is
      apparently not the explanation for the rarity of human infections with
      Trichophyton equinum. More likely, predisposing factors of the host are necessary
      in combination with a close contact to infected horses. Treatment of infected
      humans appears to be no major problem.

PMID- 9642563
TI  - [ANCA-positive lupus erythematodes profundus. Successful therapy with low dosage
      dapsone].
AB  - A 44-year-old male patient with lupus erythematosus profundus (lupus
      panniculitis) (LEP) of the right cheek/infraorbital region presented as a
      recurrent swelling. He had only anti-neutrophil-cytoplasmic antibodies (ANCA),
      which have not been previously described in association with LEP. There was no
      indication of systemic lupus erythematosus. While chloroquine produced no
      benefits, the skin lesions promptly cleared with dapsone. Step by step we reduced
      dapsone to a final dose of 50-75 mg per week. The ANCA titer decreased in
      parallel to the clinical improvement.

PMID- 9642564
TI  - [Linear and whorled nevoid hypermelanosis. Case report and review of the
      literature].
AB  - A 7 year old boy presented with linear and whorled nevoid hypermelanosis (LWNH).
      This entity, delineated in 1988, is characterized by streaked or whorled,
      frequently reticulate hyperpigmented lesions following the lines of Blaschko
      without preceding inflammation and without atrophy. The age of onset is usually
      within the first 2 years of life. Histologically, there is a mild basal cell
      hyperpigmentation with prominent melanocytes. In contrast to earlier reports, we
      observed some melanophages in the upper dermis. Associated abnormalities have
      been reported in a few patients, but were absent in our case. We present the
      clinical features, diagnostic criteria and differential diagnosis of this rare
      entity. Apparently, our patient represents the first case of LWNH in the German
      literature.

PMID- 9642565
TI  - [From the "knight stronghold" into the 21st century. Chronology of the
      dermatology department of the Spandau Hospital].

PMID- 9642566
TI  - [MELISA--in vitro test for detection of contact allergy? A comment by the German
      Contact Allergy Group].

PMID- 9642567
TI  - [What is the relevance of "individual cases" for the legislator--here with
      reference to the new communicable disease control law?].

PMID- 9642568
TI  - [Tropical dermatology, travel medicine, vaccination. I].

PMID- 9642569
TI  - To eat or not to eat: affective and physiological mechanisms in the stress-eating
      relationship.
AB  - The current study aggregated methods from the cardiovascular reactivity and
      dietary restraint paradigms in an attempt to advance our understanding of stress
      induced eating behavior. Seventy-seven female subjects completed a protocol
      consisting of distinct baseline, stress-induction, and recovery phases during
      which we monitored blood pressure, heart rate, and self-reported affect. Food was
      inconspicuously made available to participants during the recovery phase. Our
      results replicated the restraint x affect level interaction observed in the
      restraint literature, while showing that physiological measures could further
      explain distressed eating behavior. Physiological arousal was found reliably to
      predict reduced food consumption, but only among unrestrained eaters. Analysis of
      the recovery data showed that food consumption was associated with impaired
      physiological recovery rates for restrained but not for unrestrained
      participants. We believe that our results help to reconcile findings in the
      stress, eating, and dietary restraint fields and offer support for recently
      developed theories of stress-induced overeating.

PMID- 9642570
TI  - Measuring stage of change for fruit and vegetable consumption in 9- to 12-year
      old girls.
AB  - This paper presents results of the pilot-testing of a stage of change measure for
      eating fruit and vegetables (F & V) in 9- to 12-year-old girls. During troop
      meetings, 259 girls from 22 troops completed a 1-day food recognition form, a
      brief stage of change algorithm for fruit and for vegetables, and a questionnaire
      measuring psychosocial variables associated with F & V consumption. Stages for F
      & V consumption were different and MANOVAs revealed overall significant
      differences across stages for each variable. F & V intake increased with higher
      stages, as did preferences, self-efficacy for selecting, preparing, and eating F
      & V, subjective norms, and F & V preparation skills; reported barriers decreased.
      Stepwise discriminant analyses between Precontemplation and Contemplation stages
      identified fruit preferences and barriers differentiating the two stages for
      fruit consumption and subjective norms and self-efficacy differentiating the two
      stages for vegetable consumption. Barriers and F & V preparation
      responsibilities/skills were significant between the Contemplation and the Action
      stages for both fruit and vegetable consumption, with the additional variable of
      subjective norms for fruit stage and vegetable preferences for vegetable stage.
      Findings support the use of this measure to identify stage for children's
      adoption of F & V consumption behavior and as a guide for intervention
      development.

PMID- 9642571
TI  - Claustrophobia and the magnetic resonance imaging procedure.
AB  - We examined fear induced by the magnetic resonance imaging (MRI) procedure in 80
      adult patients who were undergoing the procedure for the first time. Participants
      completed self-report measures of claustrophobia, anxiety sensitivity, thoughts
      about the scan, and pain. Participants were assessed pre- and postscan, and at 1
      month follow-up. Twenty-five percent of the participants experienced moderate to
      severe anxiety during the MRI scan. Prescan scores on the Claustrophobia
      Questionnaire (CLQ: Rachman and Taylor, 1993) significantly predicted
      participants' distress during the scan: pain and anxeity sensitivity did not.
      Furthermore, CLQ scores discriminated between participants who reported panic
      during the scan and participants who did not report panic. A brief screening
      instrument consisting of six items from the 29-item CLQ is suggested. This brief
      screening instrument administered prior to the scan may help identify in advance
      those people who are most likely to experience claustrophobic fear and, in
      particular, those who panic during the MRI procedure.

PMID- 9642572
TI  - Doctors, patients, and perceived job image: an empirical study of stress and
      nurses in Singapore.
AB  - This study examined the relationships among three potential sources of stress,
      namely, demands from patients/relatives, demands from doctors, and perceived job
      image, and several work-related outcomes, namely, job satisfaction,
      organizational commitment, intention to quit, and job-induced tension.
      Respondents consist of nurses from two tertiary-care hospitals in Singapore.
      Findings of this study suggest that demands from patients/relatives, doctors, and
      perceived job image were significantly associated with nurses' job satisfaction,
      organizational commitment and job-induced tension. While demands from
      patients/relatives and perceived job image were significantly associated with
      intention to quit, the relationship between demands from doctors and nurses'
      intention to quit failed to reach statistical significance. Implications of the
      findings are discussed.

PMID- 9642573
TI  - Patients' expectations of outcome of hysterectomy and alternative treatments for
      menstrual problems.
AB  - Patients can influence treatment to the extent of securing surgery in the absence
      of medical need, but their expectations of effects of surgery are poorly
      understood. Interviews with 26 patients presenting menstrual problems without
      confirmed pathology were used to construct a questionnaire to measure
      expectations of effects of treatment. Principal-components analysis of responses
      of 200 similar patients identified six discrete areas in which improvement was
      expected, including general well-being, menstrual function, and physical
      symptoms. Expectations of harm were nonspecific and unidimensional. Component
      based scale scores showed that patients who anticipated hysterectomy expected
      more benefit, but also more harm, than those anticipating conservative
      procedures. In study 2, these different expectations were largely replicated in
      patients who were randomly allocated to provide their expectations of specific
      procedures. Patients' uniquely positive expectations of hysterectomy may help to
      explain its frequent use in the absence of pathology.

PMID- 9642574
TI  - Examination of cognitive variables relevant to sunbathing.
AB  - This study examined cognitions relevant to sunbathing decision-making in college
      aged subjects. Using Jaccard's (1981) theory of alternative behavior as a guiding
      model, 263 subjects were recruited from psychology classes and administered
      questionnaires assessing their sunbathing behavioural tendencies, attitudes
      toward sunbathing, attitudes toward reasonable behavioral alternatives to
      sunbathing, and cognitive variables underlying these attitudinal variables. The
      fits of models predicting sunbathing attitudes and sunbathing behavioural
      tendencies (evaluated using covariate structural equations modeling techniques;
      LIS-REL VIII) were good for all models tested. In contrast to previous work, the
      results of this study support the notion that young people will make their
      decisions regarding sunbathing based on the behavioral alternatives available to
      them (i.e., generally the one that they prefer most). Furthermore, the
      multivariate approach used clearly delineates the specific cognitive beliefs and
      orientations that might be targeted to change these attitudes. The relevance of
      these findings to skin cancer prevention interventions is discussed.

PMID- 9642575
TI  - Preventing, diagnosing, and treating endophthalmitis.

PMID- 9642576
TI  - Revising a myth.

PMID- 9642577
TI  - Cataract surgery training of residents in an urban and virtual environment.

PMID- 9642578
TI  - Inadvertent use of chlorhexidine as intraocular irrigation solution.

PMID- 9642579
TI  - Consultation section. Cataract surgical problem.

PMID- 9642580
TI  - Price graft-over-host technique to manage positive pressure during penetrating
      keratoplasty.
AB  - Intraoperative positive pressure with resulting iris and lens prolapse can pose a
      difficult scenario during penetrating keratoplasty. In the Price graft-over-host
      technique, the graft is sutured across the trephinated host cornea, which
      maintains a formed anterior chamber and thus avoids intraoperative complications.
      The technique was used in 33 eyes, and no primary or secondary graft failures
      occurred. Eleven episodes of acute rejection in 11 eyes were treated successfully
      with steroids.

PMID- 9642581
TI  - Intracapsular foldable posterior chamber lens implantation in eyes with posterior
      capsule tears or zonular fiber instability.
AB  - A surgical technique is described for foldable posterior chamber intraocular lens
      implantation in the capsular bag in the presence of a posterior capsule tear or
      weakened zonular fiber support. Haptics are compressed by suturing before
      endocapsular insertion, minimizing capsular and zonular fiber stress.

PMID- 9642582
TI  - Comparative study of the elevation topography of complex shapes.
AB  - PURPOSE: To compare the accuracy and precision of the elevation topography from
      two commercially available instruments using videokeratoscopy or
      rasterstereography. SETTING: University of Ottawa Eye Institute, Ottawa General
      Hospital, Ontario, Canada. METHODS: Repeated measurements of elevation topography
      of six calibrated surfaces were done with the PAR Corneal Topography System (CTS)
      and the Tomey Topographic Modeling System (TMS-1). The shapes simulated normal
      (A: aspheric, B: spherocylindric) and postsurgical corneas (C: hyperopic, D:
      myopic, E: central island, F: phototherapeutic keratectomy). Surface shapes were
      described by parametric equations. Equation parameters associated with each
      elevation measurement were determined by best-fit analysis. Measurement precision
      was assessed by the standard deviation of the difference between the fitted and
      the measured data. Fitted parameters were compared with nominal values obtained
      from an independent calibration of each surface. The root mean square error
      (RMSE) of the deviation of the fitted from the nominal surfaces was used to
      evaluate the accuracy of each instrument. RESULTS: The accuracy of the CTS
      exceeded that of the TMS-1 for all surfaces measured. The RMSE values (micron)
      were (A: 0.1, 6.5), (B: 0.3, 3.8), (C: 1.1, 11.8), (D: 5.0, 43.0), (E: 1.2, 3.2)
      and (F: 2.2, 17.5) for the CTS and TMS-1, respectively. The differences in the
      measured data from the fit surface were generally smaller with the TMS-1.
      CONCLUSION: Quantitative analysis of elevation measurements showed that the CTS
      represented surface topography more accurately than the TMS-1.

PMID- 9642583
TI  - Noncontact holmium:YAG laser thermal keratoplasty for hyperopia.
AB  - PURPOSE: To describe our experience with noncontact holmium:YAG laser thermal
      keratoplasty (Ho:YAG LTK). SETTING: Refractive Surgery and Cornea Department,
      Clinica de Ojos Dr. Nano, Buenos Aires, Argentina. METHODS: In this retrospective
      study, 182 hyperopic eyes from 116 patients were treated with noncontact Ho:YAG
      LTK. Mean age was 50 years +/- 7 (SD), and the spherical equivalent (SE) of the
      subjective mean refraction (SMR) was +2.50 +/- 0.87 diopters (D). Eyes with
      corneal power of more than 45 D, corneal pachymetry thicker than 550 microns, and
      previous corneal surgery or disease were excluded. Holmium:YAG laser parameters
      include one to three rings of eight spots arranged in a radial and symmetrical
      array. Pulse energy was 240 mJ, with five pulses per spot. Patients were followed
      for 12 months. RESULTS: The mean uncorrected visual acuity from 3 to 12 months
      was 20/40 (20/200 to 20/25), improving an average of three Snellen lines. Mean
      best spectacle-corrected visual acuity was 20/25 at all postoperative
      examinations, the same as preoperatively. Mean SE of the SMR was +1.50 +/- 0.98 D
      (range -0.75 to +4.50 D) at 6 months and +1.25 +/- 0.96 D (+0.25 to +3.25 D) at 1
      year. After 9 months, 17% of operated eyes were retreated. CONCLUSION: In this
      study, Ho:YAG LTK was safe and effective, provided satisfactory correction of low
      hyperopia, and had a low complication rate. Good patient selection is the key to
      obtaining good results.

PMID- 9642584
TI  - Laser in situ keratomileusis for myopia and astigmatism: 6 month results.
AB  - PURPOSE: To evaluate the visual and refractive results of laser in situ
      keratomileusis (LASIK) for mild to moderate myopia with or without astigmatism.
      SETTING: Barnet-Dulaney Eye Center, Phoenix, Arizona, USA. METHODS: Data were
      prospectively collected on 124 consecutive eyes having LASIK over 12 weeks. Eyes
      with a preoperative spherical equivalent (SE) from -1.35 to -10.00 diopters (D)
      (mean -4.81 D +/- 2.21 [SD]) and cylinder from 0 to 5.00 D (mean 1.12 +/- 1.12 D)
      were entered in the study. Thirty-one eyes had spherical corrections. Ninety
      three eyes had spherocylinder corrections; preoperative astigmatism in these eyes
      ranged from 0.50 to 5.00 D (mean 1.47 +/- 1.09 D). Surgery included creation of a
      corneal flap using an automated microkeratome with a 160 microns plate followed
      by photoablation on the exposed stromal bed. Photoablation was performed using
      five zones varying from 5.0 to 6.6 mm in eyes with 6.25 D of myopia or less and
      with five passes at a 5.0 mm zone in eyes with 6.50 D of myopia or more.
      Astigmatism was corrected using a single-pass ablation through a 6.0 mm slit of
      varying diameter. RESULTS: Six month follow-up was obtained in 89 eyes (72%). All
      eyes were completely re-epithelialized by the first postoperative day.
      Uncorrected visual acuity was 20/40 or better in 81% of eyes at 1 day and in 91%
      at 6 months. At 6 months, the mean SE was -0.35 +/- 0.77 D; 83% were within +/-
      1.00 D of plano. Postoperative astigmatism in the 93 eyes having cylinder
      correction ranged from 0 to 1.22 D (mean 0.38 +/- 0.42 D). No eye lost more than
      two lines of best spectacle-corrected visual acuity. Three eyes (2%) required
      surgical intervention for cap problems. Visually significant corneal haze was not
      observed. CONCLUSION: In eyes with myopia with or without astigmatism, LASIK
      provided rapid visual recovery with satisfactory visual and refractive outcomes.
      The effect of LASIK on visual function (night glare, contrast sensitivity) awaits
      further study.

PMID- 9642585
TI  - Astigmatic keratotomy effect of single-hinge, clear corneal incisions using
      various preincision lengths.
AB  - PURPOSE: To investigate the astigmatic keratotomy effect of a modified single
      hinge cataract incision. SETTING: Department of Ophthalmology, San Juan de Dios
      Hospital, Tenerife, Spain. METHODS: This prospective study evaluated the
      astigmatic changes resulting from preincision grooves of less than 40, 45, and 55
      degrees in arc length used with a single-hinge, self-sealing cataract incision in
      144 eyes that had against-the-rule corneal astigmatism preoperatively. The
      intended 90% depth preincision was centered on the steep meridian and lengthened
      according to the amount of preoperative astigmatism. Outcome measurements were
      obtained by calculating the surgically induced astigmatism vectors and the
      postoperative keratometry changes 1 day, 1 week, and 1, 3, and 6 months after
      surgery. RESULTS: Three months postoperatively, astigmatism decreased by 0.03,
      0.30, and 0.68 diopter in the less than 40, 45, and 55 degree incision length
      groups, respectively. The differences between the 45 and 55 degree groups and the
      less than 40 degree group was statistically significant (P < .05). Similar
      results were observed 6 months after surgery. CONCLUSION: The astigmatic
      preincision modification produced statistically significant increasing reductions
      in preoperative astigmatism according to preincision length.

PMID- 9642586
TI  - Retinal detachment after cataract extraction in myopic eyes.
AB  - PURPOSE: To determine the incidence of retinal detachment (RD) after cataract
      extraction in people 40 years of age or older with axial myopia (i.e., axial
      length > or = 25.5 mm). SETTING: Fifteen Danish eye clinics. METHODS: Two hundred
      forty-five eyes had cataract extraction performed at 15 eye clinics; 237 eyes had
      extracapsular cataract extraction (ECCE) and 8 eyes, intracapsular cataract
      extraction (ICCE). Postoperative data were reported by the practicing
      ophthalmologists. Mean follow-up was 27 months (range 14 to 32 months). RESULTS:
      Five RDs occurred in the 245 eyes (2.0%). Excluding the ICCE cases and the two
      cases of combined cornea transplantation and ECCE, RD occurred in 4 of the 235
      eyes that had ECCE (1.7%). The incidence after ECCE with posterior chamber lens
      implantation was 1.4%. Complete postoperative status was reported on 158 eyes.
      Forty-eight eyes (30.4%) had a neodymium:YAG capsulotomy and 3 (6.0%) developed
      an RD 1, 3.5, and 21 months after the capsulotomy. CONCLUSION: The RD incidence
      after ECCE with posterior chamber lens implantation was low but higher than that
      in unselected populations. The incidence increased after laser capsulotomy.

PMID- 9642587
TI  - Retinal detachment following phacoemulsification in highly myopic cataract
      patients.
AB  - PURPOSE: To assess whether modern, small incision phacoemulsification techniques
      significantly reduce the retinal detachment (RD) risk in highly myopic patients
      who have visually significant cataracts. SETTING: University-associated
      ophthalmology practice. METHODS: This retrospective study included 80 eyes in 61
      patients with preoperative myopia of 7.00 diopters (D) or more. Sixty-four eyes
      had an axial length of 25.0 mm or greater. All surgery was performed superiorly
      using a frown-shaped, self-sealing, scleral tunnel. The incision size ranged from
      3.0 to 5.0 mm. Capsulorhexis was performed and then four-quadrant cracking
      phacoemulsification. The posterior capsule was routinely polished. A posterior
      chamber intraocular lens (IOL) was implanted in the capsular bag in all cases.
      RESULTS: No RDs occurred during the mean follow-up of 43 months (range 9 to 77
      months) or the mean follow-up after neodymium:YAG capsulotomy of 20 months. No
      intraoperative complications occurred. Seventy-one of 80 eyes (89%) achieved best
      spectacle-corrected visual acuity of 20/25 or better. CONCLUSIONS: Retinal
      detachments following modern cataract surgery in high myopia are much less common
      than previously reported. We attribute this to small incision size, continued
      maintenance of the anterior chamber, posterior chamber IOL implantation, and lack
      of intraoperative complications.

PMID- 9642588
TI  - Phacoemulsification, intraocular lens implantation, and trabeculotomy to treat
      pseudoexfoliation syndrome.
AB  - PURPOSES: To determine the long-term risk/benefit ratio of phacoemulsification
      and intraocular lens (IOL) implantation combined with trabeculotomy to manage
      eyes with pseudoexfoliation syndrome and co-existing cataract. SETTING:
      Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School
      of Medicine; Kurihara Eye Clinic; Departments of Ophthalmology, Tenri Hospital,
      Kumamoto University, and Matsue Red Hospital; Nagata Eye Clinic, Japan. METHODS:
      This multicenter retrospective study comprised 49 eyes of 36 patients with
      pseudoexfoliation syndrome and co-existing cataract who had the combined
      procedure for uncontrolled intraocular pressure (IOP) (> 21 mm Hg) even on
      antiglaucoma medication. RESULTS: After a mean follow-up of 20.0 months +/- 13.2
      (SD), IOP in all 49 eyes was well controlled (< or = 21 mm Hg). Mean IOP at the
      final examination was 14.6 +/- 2.6 mm Hg on a mean of 0.9 +/- 0.8 glaucoma
      medications. Complications included an IOP spike in 11 eyes and fibrin exudation
      in 1 eye. CONCLUSION: Phacoemulsification and IOL implantation combined with
      trabeculotomy was an effective treatment for patients with pseudoexfoliation
      syndrome and cataract.

PMID- 9642589
TI  - Phacoemulsification in eyes with pseudoexfoliation.
AB  - PURPOSE: To compare intraoperative and postoperative complications in eyes with
      and without pseudoexfoliation having cataract surgery by phacoemulsification.
      SETTING: Department of Ophthalmology, National Hospital, Oslo, Norway. METHODS:
      Of 1152 consecutive phacoemulsification procedures, 164 cases with
      pseudoexfoliation (Group 1) and 916 cases without (Group 2) were followed for 4
      months after cataract surgery in a prospective study. Of all cataract operations
      performed during that time, 96.2% were phacoemulsification procedures; 90.4 and
      97.4% in eyes with and without pseudoexfoliation, respectively (P < .0005).
      RESULTS: The frequency of capsular/zonular tear or vitreous loss was 9.6 and 3.7%
      in Groups 1 and 2, respectively (P = .0002). A visual acuity of 0.5 or better was
      achieved in 86.5% of eyes in Group 1 and 92.4% in Group 2 (P = .02). There were
      no statistically significant between-group differences in the frequency of a
      postoperative inflammatory response 1 day (6.7 versus 4.4%), 1 week (2.4 versus
      1.6%), or 4 months (1.8 versus 0.9%) postoperatively. CONCLUSION:
      Phacoemulsification was safe in most eyes with pseudoexfoliation even though
      significantly more complications occurred intraoperatively in these eyes. The low
      frequency of an inflammatory response indicates that the presence of
      pseudoexfoliation does not significantly increase the risk of inflammation.

PMID- 9642590
TI  - Risk of acute suprachoroidal hemorrhage with phacoemulsification.
AB  - PURPOSE: To establish whether small incision cataract surgery with
      phacoemulsification decreases the risk of acute suprachoroidal hemorrhage (ASCH)
      compared with traditional nucleus expression by extracapsular cataract extraction
      (ECCE). SETTING: St. Erik Eye Hospital, Stockholm, Sweden. METHODS: A
      retrospective study was done on the incidence of ASCH in cataract surgery between
      July 1990 and July 1996. During this period, 37,565 cataract extractions
      (phacoemulsification and ECCE) were performed at St. Erik Eye Hospital, combined
      procedures excluded. The criteria for diagnosis were the suspicion of ASCH during
      surgery and a verified diagnosis via an expulsive hemorrhage into the wound (4
      cases), postoperative ultrasonic examination (20 cases), or a choroidal mass on
      performing ophthalmoscopy together with a postoperative history alluding to the
      diagnosis (2 cases). RESULTS: Twenty-six eyes were identified with ASCH,
      including 7 during phacoemulsification and 19 during ECCE. The incidence of ASCH
      was 0.03% in the 23,213 phacoemulsification cases and 0.13% in the 14,352 ECCE
      cases. The difference was statistically significant (P = .0003; chi-square test).
      CONCLUSION: Small incision surgery with phacoemulsification decreased the risk of
      ASCH in cataract surgery compared with the traditional nucleus expression
      technique.

PMID- 9642591
TI  - Vitreous loss during conversion from conventional extracapsular cataract
      extraction to phacoemulsification.
AB  - PURPOSE: To study the outcome of vitreous loss among senior surgeons converting
      from conventional extracapsular cataract extraction (ECCE) to
      phacoemulsification. SETTING: A university teaching hospital in the United
      Kingdom. METHODS: A retrospective analysis of 87 planned cataract extractions
      performed from January 1992 to December 1996 and complicated by vitreous loss was
      done. Outcome measures included postoperative complication rates and visual
      acuity. RESULTS: During the study, vitreous loss occurred in 39 patients having
      ECCE and in 48 having phacoemulsification; the latter group included 8 patients
      with dropped nucleus. Postoperative complications included cystoid macular edema
      (18.7% of phaco patients, 30.8% of ECCE patients), retinal detachment (2.1% of
      phaco patients, 5.1% of ECCE patients), and expulsive hemorrhage (5.1% of ECCE
      patients). Phaco patients had higher rates of postoperative corneal edema (27.1%)
      than ECCE patients (12.8%) and transient intraocular pressure elevation (33.3%)
      versus 20.5%) but were more likely to receive posterior chamber intraocular
      lenses (70.8% versus 35.9%; P = .0024, chi-square test). After excluding pre
      existing diseases, 83.3% of phaco patients and 67.6% of ECCE patients achieved a
      visual acuity of 6/12 or better. CONCLUSIONS: With careful patient selection,
      experienced extracapsular surgeons converting to phacoemulsification can achieve
      favorable results even in the presence of complications such as vitreous loss or
      dropped nucleus.

PMID- 9642592
TI  - Phacoemulsification cataract surgery in vitrectomized eyes.
AB  - PURPOSE: To determine the problems, safety, and results of phacoemulsification
      cataract surgery in previously vitrectomized eyes. SETTING: Department of
      Ophthalmology of Galdacano Hospital, Galdacano, Spain. METHODS: In this
      prospective study, phacoemulsification was performed in 23 eyes that had had
      vitrectomy between February 1992 and May 1994. Surgical and postsurgical
      difficulties and complications and visual acuity results were analyzed. Follow-up
      ranged from 12 to 24 months. RESULTS: The incidence of surgical problems and
      complications was higher than usual: 7 eyes presented small pupil size (< 3.0
      mm); sudden changes in anterior chamber depth and pupil size during surgery
      occurred in 6 eyes; unusual mobility and flaccidity of the posterior capsule was
      observed in 6 cases, which was associated with posterior subcapsular cataract and
      young age (< 50 years); posterior capsule tear occurred in 2 eyes, 1 of which
      required anterior vitrectomy. Postoperatively, best visual acuity improved two
      Snellen lines or more in 17 eyes (73.91%), did not change in 3 (13.04%), and
      worsened in 3. CONCLUSION: Phacoemulsification in vitrectomized eyes presented
      more problems and complications than usual. However, it seems to be safer than
      manual extracapsular surgery because it minimized the risk of intraoperative eye
      hypotony or collapse.

PMID- 9642593
TI  - Anterior chamber metal fragments after phacoemulsification surgery.
AB  - PURPOSE: To determine whether metal fragments can be shaken loose from phaco
      needles during surgery and embed in the iris. SETTING: Private practice, Vernon,
      British Columbia, Canada, and scanning electron microscope laboratory, Mastel
      Precision, Rapid City, South Dakota, USA. METHODS: The surfaces and rims of new
      and used phaco needles and the lumens of halved new needles were examined by
      scanning electron microscopy (SEM). To determine whether the fragments on the
      phaco needles were approximately the same size as those seen in the iris, a
      photograph of an eye with metal fragments imbedded in the iris was projected and
      the image size of the metal fragments approximated by using their magnification
      value. The magnification scale of the SEM images was used to determine the size
      of the metal fragments photographed on the phaco needles. RESULTS: The SEM
      studies of new phaco needles revealed tiny fragments of metal firmly adherent to
      the interior, exterior, and rim surfaces. No fragments were detected on the
      surfaces of the used phaco needles. Two metal fragments in the eye photograph
      were calculated to be 0.20 x 0.20 mm and 0.15 x 0.20 mm. Those in the SEM photos
      were calculated to be 0.03 to 0.10 mm. CONCLUSION: Althogh SEM of new titanium
      phaco needles revealed adherent metal fragments on their lathed surfaces, no
      fragments were found on used phaco needles. The iris fragments calculated from a
      projected photograph were slightly larger than those from the SEM micrographs,
      supporting the conclusion that annealed metal fragments shook loose from the
      phaco needles. This indicates that ultrasonic activation of a new phaco needle
      with metal fragments annealed to its surface causes fragments to release and
      embed in the iris.

PMID- 9642594
TI  - Prospective, randomized trial comparing Micro Visc Plus and Healon GV in routine
      phacoemulsification.
AB  - PURPOSE: To compare the safety and efficacy of two sodium hyaluronate
      viscoelastics--MicroVisc Plus and Healon GV--in routine phacoemulsification and
      evaluate whether these more viscous and cohesive agents offer benefits compared
      to viscoelastics of standard viscosity and cohesion. SETTING: York Finch Eye
      Associates and York Finch General Hospital, Toronto, Canada. METHODS: An
      unmasked, randomized, prospective clinical trial of 100 eyes of 100 patients
      having routine phacoemulsification with intraocular lens implantation was
      conducted comparing the safety and efficacy of MicroVisc Plus with those of
      Healon GV. Preoperative and 6 hour, 1 and 5 days, and 1 and 6 month postoperative
      assessments included acuity, corneal thickness, intraocular pressure, and surgeon
      assessment of the task-facilitating efficacy of the viscoelastics. Results were
      compared with those of a similar trial of MicroVisc and Healon. RESULTS: There
      were no statistically significant differences between the two treatment groups at
      any follow-up. The surgeon judged the two viscoelastics to be equivalent,
      although somewhat different in facilitating surgery. There was significantly less
      transient postoperative corneal thickening in the Healon GV/MicroVisc Plus group
      than in the Healon/MicroVisc group. CONCLUSIONS: Healon GV and MicroVisc Plus
      were safe and provided equal outcomes based on the parameters assessed. MicroVisc
      Plus' higher zero-shear viscosity caused it to behave slightly differently than
      Healon GV during surgery. More viscous, cohesive viscoelastics may increase
      surgical safety.

PMID- 9642595
TI  - Diagnosis of infectious endophthalmitis after cataract surgery by polymerase
      chain reaction.
AB  - PURPOSE: To ascertain whether the use of the polymerase chain reaction (PCR)
      technique leads to more rapid diagnosis of infectious endophthalmitis after
      cataract surgery. SETTING: University Eye Clinic Regensburg, Germany. METHODS:
      The aqueous humor and vitreous of 16 eyes with infectious endophthalmitis (10
      acute, 6 delayed) were evaluated by microscopy, diagnostic culture, and PCR to
      detect the infectious agent. RESULTS: Microscopy of the vitreous was positive in
      3 eyes and the culture media results were positive in 7 eyes, all with acute
      endophthalmitis. Significantly fewer positive results were obtained in the
      aqueous humor. Using PCR, an infectious agent was detected in the aqueous humor
      of all 16 eyes and in the vitreous of 14. The vitreous sample was negative in 2
      eyes with delayed endophthalmitis. CONCLUSIONS: Detection of the infectious agent
      was more successful using PCR than using conventional microbiological tests,
      especially in the diagnosis of delayed endophthalmitis where the pathogen was
      detected in the aqueous humor in all eyes.

PMID- 9642596
TI  - Detachment of Descemet's membrane.
AB  - PURPOSE: To determine predisposing factors, best method of treatment, and the
      final outcome in cases of Descemet's membrane detachment. SETTING: A tertiary
      care teaching eye hospital. METHODS: All cases of Descemet's detachment from
      January 1986 to May 1994 were retrospectively reviewed. Twelve eyes of 11
      patients with partial or total detachment of Descemet's membrane were identified.
      Patients with small localized detachments at the incision area were excluded.
      RESULTS: All but one patient had surgical repair. Ten eyes had successful
      reattachment after up to four attempts at repair. Methods of repair included
      intracameral air or sulfur hexafluoride (SF6) 20% gas, with or without corneal
      sutures. After a followup of 3 to 79 months, eight eyes retained clear corneas,
      four eyes developed corneal edema and scarring, and two required penetrating
      keratoplasty. No definite predisposing factor could be identified, although four
      eyes had preoperative diagnoses of glaucoma and recent corneal edema. CONCLUSION:
      Surgical repair with injection of intracameral air or SF6 20% was successful in
      most cases of Descemet's membrane detachment. A preoperative diagnosis of
      glaucoma and a recent episode of corneal edema may increase the risk of
      detachment.

PMID- 9642597
TI  - Analysis of preoperative factors predictive of visual acuity in axial myopia.
AB  - PURPOSE: To identify the factors predicting visual acuity after cataract surgery
      in patients with high myopia. SETTING: Departments of Ophthalmology, Showa
      University School of Medicine and Showa University Fujigaoka Hospital, Kanagawa,
      Japan. METHODS: Stepwise regression analysis was used to identify the factors
      determining the visual acuity in 940 eyes with an axial length of 27.0 mm or
      longer having cataract surgery. Using a formula derived from the stepwise
      regression analysis, the predicted postoperative visual acuity was compared with
      the actual value measured in another group of 104 eyes. RESULTS: Five factors
      were identified to significantly determine postoperative visual acuity: axial
      length, age, corneal opacity, refractive power of the cornea, and history of
      retinal detachment surgery. There was a significant relationship between
      predicted and actual postoperative visual acuities (r = .51, P < .001).
      Postoperative visual acuity was similar in 63% of cases. CONCLUSION: The results
      showed that at least five factors determine visual acuity after cataract surgery
      in patients with high myopia.

PMID- 9642598
TI  - Comparison of ciliary sulcus fixation techniques for posterior chamber
      intraocular lenses.
AB  - OBJECTIVE: To anatomically and histologically evaluate suturing techniques for
      sulcus fixation of posterior chamber intraocular lenses. SETTING: Kitano
      Hospital, Osaka, Japan. METHODS: The reproducibility of three suturing techniques
      (perpendicular to the eye wall; parallel to the iris; midway between
      perpendicular to the eye wall and parallel to the iris) were evaluated in a
      postmortem eye. Histologic sections of another eye and ultrasound biomicroscopy
      (UBM) images of 21 normal eyes were evaluated to determine the safety zone for
      the needle to avoid damaging adjacent structures. RESULTS: The ciliary sulcus was
      completely penetrated in the three techniques in 100, 40, and 70% of cases,
      respectively. The histologic sections and the UBM images showed that when sutures
      were placed perpendicular to the eye wall, there was the possibility of
      postoperative angle closure and suturing parallel to the iris might damage
      adjacent structures because of a narrow safety zone. CONCLUSIONS: The needle
      should penetrate obliquely, as in the technique in which the suturing is midway
      between perpendicular to the eye wall and parallel to the iris. This technique
      provides better reproducibility and causes less damage to adjacent tissue.

PMID- 9642599
TI  - Outcomes and ocular growth rates after intraocular lens implantation in the first
      2 years of life.
AB  - PURPOSE: To evaluate the outcomes and ocular growth after intraocular lens (IOL)
      implantation in the first 2 years of life. SETTING: University-affiliated eye
      institute. METHODS: The medical records of consecutive children under 24 months
      of age who had cataract extraction with IOL implantation were reviewed. Change in
      axial length over time, postoperative complications, need for additional surgery,
      predicted versus actual postoperative refraction, and visual outcomes were
      recorded. Complication rates were compared with those in a similar group of age
      matched patients who were left aphakic at the time of surgery. RESULTS: Twenty
      two eyes of 17 patients aged 12 days to 22 months had IOL implantation. Length of
      follow-up ranged from 2 to 36 months (mean 14 months). Visual acuity measurement,
      limited to fixation-preference testing in most patients, revealed amblyopia in
      the operated eye in the majority of cases. Postoperative refractive error,
      predicted using the Holladay formula, showed a mean error in prediction of 1.5
      diopters (D) (range -1.8 to 4.1 D). Serial axial lengths in 11 patients with a
      mean follow-up of 20 months showed no significant difference in growth in the
      fellow versus the operated eye. There was no significant difference in
      complication rates between pseudophakic patients and the age-matched aphakic
      group. However, in 14 of 32 aphakic eyes (44%), a notation in the chart indicated
      that the patient had stopped wearing glasses or contact lenses for at least 2
      months. CONCLUSION: Intraocular lens implantation appeared to be a safe and
      effective alternative to contact lens or spectacle correction of aphakia in
      children younger than 2 years of age. It may aid amblyopia treatment by
      eliminating periods of uncorrected aphakia.

PMID- 9642600
TI  - Prospective evaluation of topical versus retrobulbar anesthesia: a converting
      surgeon's experience.
AB  - PURPOSE: To evaluate and compare the efficacy of topical versus retrobulbar
      anesthesia for cataract surgery performed by a surgeon newly converting to the
      topical technique. SETTING: Department of Ophthalmology, Moran Eye Center,
      University of Utah, Salt Lake City, Utah, USA. METHODS: Ninety patients were
      prospectively assigned by permuted block restricted randomization to receive
      topical (Group 1; n = 45) or retrobulbar (Group 2; n = 45) anesthesia. Group 1
      received topical bupivacaine 0.75% and intravenous midazolam and fentanyl for
      anesthesia. Group 2 received intravenous methohexital followed by retrobulbar
      block with an equal mixture of lidocaine 2% and bupivacaine 0.75% plus
      hyaluronidase 150 units. A visual pain analog scale was used to assess the degree
      of pain during anesthesia administration and surgery and postoperatively. The
      degree to which eye movement, touch, and light caused patient discomfort was
      assessed. Intraoperative conditions and complications were recorded. RESULTS:
      Intraoperative operating conditions were significantly better in Group 2 (P <
      .05). There was a small but statistically significant difference in the degree of
      discomfort during anesthesia administration and surgery (P < .05). There was no
      difference in postoperative discomfort. Chemosis, subconjunctival hemorrhage, and
      eyelid hemorrhage occurred only in Group 2, in which there was one retrobulbar
      hemorrhage. Although eyelid squeezing and ocular motility were present more
      frequently in Group 1, neither was a problem to the surgeon. CONCLUSION: Cataract
      surgery was safely performed by a surgeon converting to topical anesthesia. After
      a distinct learning curve, the procedure was performed with minimal patient
      discomfort. Surgical training and patient preparation are the key to safe use of
      topical anesthesia.

PMID- 9642601
TI  - Paradoxical response to photorefractive treatment for postkeratoplasty
      astigmatism.
AB  - A 42-year-old woman with functionally disabling postkeratoplasty astigmatism in
      her right eye 3 years after corneal transplantation for keratoconus received
      photorefractive keratectomy for high astigmatism in that eye. This did not reduce
      her astigmatism. The procedure was repeated and corneal astigmatism paradoxically
      increased. The forces within the pseudo-optical ring that cause and maintain
      astigmatism in corneal transplants may be a significant factor in the
      unpredictable response of some corneal transplants to excimer photorefractive
      astigmatism correction.

PMID- 9642602
TI  - Delayed-onset Pseudomonas stutzeri endophthalmitis after uncomplicated cataract
      surgery.
AB  - An 88-year-old woman had uneventful extracapsular cataract extraction with
      posterior chamber intraocular lens (IOL) implantation in her right eye. Seven
      weeks later, an anterior vitrectomy with removal of the IOL was performed because
      of endophthalmitis resistant to topical and systemic amoxicillin, cephalosporin,
      aminoglycoside, and steroids. Microbiological examination of the vitreous biopsy,
      capsule, and anterior chamber fluid disclosed Pseudomonas stutzeri, gram-negative
      nonfermentative bacteria sensitive to tetracycline, ceftazidime, gentamicin,
      ofloxacin, and piperacillin. Pseudomonas stutzeri should be considered in the
      treatment of delayed-onset endophthalmitis.

PMID- 9642603
TI  - Traumatic cataract with a ruptured posterior capsule from a nonpenetrating ocular
      injury.
AB  - An 11-year-old boy had posterior lens capsule rupture resulting from a
      nonpenetrating (blunt trauma) injury to the eye. A rapidly developing cataract
      required pars plana lensectomy. This report suggests that posterior capsule
      rupture may occur secondary to blunt trauma and progressive cataract formation
      after posterior capsule rupture may require surgery soon after the injury.

PMID- 9642604
TI  - Anterior capsulotomy created by radiofrequency endodiathermy and continuous
      curvilinear posterior capsulorhexis in a patient with intumescent cataract and
      primary capsular fibrosis.
AB  - A 62-year-old woman with intumescent cataract and primary posterior capsular
      fibrosis was operated on using two different techniques to create continuous
      curvilinear capsule openings in the same eye. The biomicroscopic appearance of
      the edge after continuous tear and radiofrequency endodiathermy capsulotomy were
      compared.

PMID- 9642605
TI  - Antibiotic treatment in preterm labor and intact membranes: a randomized, double
      blinded, placebo-controlled trial.
AB  - Although an association between microbial invasion of amniotic cavity and preterm
      birth has been extensively demonstrated, there is conflicting evidence regarding
      the benefits of antibiotic therapy in patients with preterm labor and intact
      membranes. We attempted to assess the efficacy of amoxicillin and erythromycin on
      pregnancy outcome in those patients. A randomized, double-blinded, placebo
      controlled trial was designed and implemented. A total of 196 patients with
      singleton pregnancies and preterm labor with intact membranes (22-36 weeks) were
      randomly allocated to receive either antibiotics or placebo, plus adjunctive
      parenteral tocolysis, and 173 patients (antibiotics group n = 83 vs. placebo
      group n = 90) completed the treatment. The overall prevalence of microbial
      invasion of the amniotic cavity was 5.2% (9/173). No significant difference
      between both groups was found in maternal outcomes, including duration of
      randomization-to-delivery interval, frequency of preterm delivery, and frequency
      of clinical chorioamnionitis and endometritis. Rate of cesarean section was
      significantly higher in the placebo group (28% vs. 12%). Regarding neonatal
      outcome, no significant difference was detected between both groups in neonatal
      death, respiratory distress syndrome, proven sepsis, and birthweight. Suspected
      sepsis was significantly more frequent in the placebo group (6/90 vs. 0/78). The
      results of this trial indicate that amoxicillin and erythromycin do not prolong
      pregnancy in patients with preterm labor and intact membranes. A significant
      reduction in the rate of cesarean section was observed in patients receiving
      antibiotics. A significant reduction in the rate of neonatal suspected sepsis was
      also demonstrated.

PMID- 9642606
TI  - New triple screen test for Down syndrome: combined urine analytes and serum AFP.
AB  - In this study we report a new triple test that combines serum AFP, urine beta
      core fragment of hCG, total urine estriol, and maternal age for calculating
      individual Down syndrome odds in the second trimester. The urine beta-core
      fragment/estriol ratio was used as a single screening variable. Analyte levels
      were measured prospectively in 10 Down syndrome cases and 346 normals. Individual
      Down syndrome odds were calculated by multiplying the product of the Down
      syndrome likelihood ratios of serum AFP and urine beta-core/estriol levels by the
      age-related midtrimester risk. The screening efficiency of an algorithm that
      combines urine beta-core/estriol with maternal age was compared to one that
      included serum AFP data. A 90% detection rate for Down syndrome was obtained at a
      4.65% false positive rate. This was superior to the 75% sensitivity at 5% false
      positive rate observed when beta-core/estriol and age alone were used. This new
      triple test has a higher screening efficiency than that generally reported for
      the traditional serum triple screen and other urine tests, and it also provides
      information on the risk of neural tube defects. If confirmed in larger trials,
      the new algorithm could be used as an alternative to the traditional serum triple
      screen.

PMID- 9642607
TI  - Efficacy of intravaginal misoprostol in second-trimester pregnancy termination: a
      randomized controlled trial.
AB  - A prospective randomized, double-blind, controlled clinical trial to compare the
      clinical efficacy and side effects of intravaginal misoprostol with the
      traditional prostaglandin, gemeprost, in second-trimester pregnancy interruption
      was conducted. A sample size of 100 women was calculated to demonstrate that
      misoprostol was as effective as gemeprost in achieving delivery within 24 hours
      (alpha = 0.1, 80% power). Women were recruited with fetal death in utero, severe
      fetal anomaly, or psychosocial pregnancy termination between 14 and 28 weeks
      gestation and randomized to receive either 1 mg gemeprost 3 hourly for 5 doses,
      or 200 mcg misoprostol 6 hourly for 4 doses, intravaginally. The therapeutic
      regimens were repeated if undelivered by 24 hours. Those undelivered after 48
      hours received an extra-amniotic PGF2 alpha infusion. The median gestation at
      recruitment was identical: gemeprost 19 weeks (IQ 17-22 weeks) vs. misoprostol 19
      weeks (IQ 17-21 weeks), P = 0.887. Delivery within 24 hours occurred in 75.1% of
      women receiving gemeprost and 74.9% receiving misoprostol (P = 1.0). The median
      time from prostaglandin commencement to delivery was similar: gemeprost 13.7
      hours (IQ 9.0-23.5 hours) vs. misoprostol 16.9 hours (IQ 10.3-23.5 hours), P =
      0.769. A significant reduction in the incidence of vomiting in women randomized
      to misoprostol occurred (34% vs. 13.2%, P = 0.017). There was no significant
      difference in the incidence of maternal fever > 37.5 degrees C, nausea, diarrhea,
      or placental retention. A 200-fold pharmaceutical cost advantage was observed
      with the use of misoprostol compared with gemeprost. Intravaginal misoprostol
      performs as effectively as gemeprost in achieving delivery in the second
      trimester without increase in adverse effects and displaying a significant cost
      advantage.

PMID- 9642608
TI  - Superior mesenteric artery flow velocity waveforms in small for gestational age
      fetuses.
AB  - The objective of this study was to analyze the superior mesenteric artery flow
      velocity waveforms in small-for-gestational-age fetuses and to compare its
      contribution in their management with that already provided by the middle
      cerebral artery and umbilical artery flow velocity waveforms. Middle cerebral
      artery, umbilical artery, and superior mesenteric artery flow velocity waveforms
      were prospectively obtained in 41 small-for-gestational-age fetuses with color
      Doppler ultrasonography. The pulsatility index was used to quantify the
      waveforms. Poor perinatal outcome was defined by cesarean section for fetal
      distress, perinatal death, need for assisted ventilation, and necrotizing
      enterocolitis. In the small-for-gestational age fetuses, the middle cerebral
      artery pulsatility index was abnormal in 22/41, the umbilical artery in 26/41,
      and the superior mesenteric artery in 17/41. Coincident with abnormal umbilical
      and middle cerebral artery flow velocity waveforms were greater occurrences of
      poor perinatal outcome. The abnormality of an increased pulsatility index in the
      superior mesenteric artery velocity waveforms of small-for-gestational-age
      fetuses suggests greater vascular resistance and an overall reduction in visceral
      perfusion. However, the study of the superior mesenteric artery only seemed to
      support the information already provided for by the middle cerebral and umbilical
      arteries.

PMID- 9642609
TI  - Statistical models of outcome in malpractice lawsuits involving death or
      neurologically impaired infants.
AB  - The objective was to determine whether factors could be identified in medical and
      legal records that are associated with the successful defense of obstetrical
      malpractice cases involving the death or neurological impairment of infants.
      Obstetrical claims (169) closed by PROMUTUAL between January 1, 1990, and
      December 31, 1994, were retrospectively abstracted and analyzed to identify
      associations between medical and legal factors, and the medicolegal outcome.
      Multivariable analysis identifies that the use of pitocin, diagnosis of asphyxia,
      a delay in delivery, and the use of multiple defense expert witnesses decreased
      the chances of a successful defense. Two statistical models explaining indemnity
      payment were developed. The first, based on medical outcome, showed an increased
      indemnity payment when a case involved major neurological deficits, diagnosis of
      asphyxia, newborn seizures, later year of delivery, and participation of a
      particular defense firm. Perinatal or childhood death and the use of pitocin were
      indicators of a decrease in payment. The second model was based on long-term care
      requirements. In this model, indicators of increased indemnity payment were:
      nonreassuring intrapartum fetal heart rate tracing, later year of delivery,
      intensity of long-term care required, and participation of a particular defense
      law firm. Perinatal or childhood death, the use of pitocin, and settlement date
      increasingly removed from the occurrence date were the determinants of decreased
      payments in this model. Finally, the presence of major neurological deficits, the
      prolongation of a case, and the involvement of multiple law firms and defense
      witnesses increased the expense charged to and paid by the insurance company.
      Using the medical, legal, and financial data relevant to 169 obstetrical cases
      closed by one malpractice insurance carrier between 1990 and 1994, statistical
      models with potential predictive values for future malpractice claims involving
      neurologically impaired infants were constructed. These models may help determine
      in advance the chance a future case has for successful defense and the likely
      amount of expense and indemnity dollars that will be paid out to settle and
      defend it.

PMID- 9642610
TI  - Subgaleal hemorrhage in a premature infant with congenital diaphragmatic hernia
      following vacuum-assisted delivery.
AB  - An infant with congenital diaphragmatic hernia was delivered by vacuum
      extraction, with a resultant subgaleal hemorrhage that excluded him from ECMO.
      The literature regarding vacuum-assisted delivery and birth trauma is reviewed in
      the context of congenital anomalies that may require ECMO support, and
      recommendations for perinatal management are suggested.

PMID- 9642611
TI  - Variation in use of corticosteroids among infants < or = 1,500 grams across
      hospitals in three states.
AB  - We identified factors associated with no antenatal corticosteroid treatment among
      1,369 women who delivered infants < or = 1,500 g and < 34 weeks gestation, 1991
      1993. At four hospitals, infants weighing 500-1,500 g were enrolled. Information
      regarding corticosteroid use, maternal characteristics, and perinatal events were
      obtained. Factors associated with no corticosteroid treatment were examined in
      unadjusted and adjusted logistic regression models. Overall, 693 (50.6%) women
      did not receive corticosteroids. Two hospitals had higher rates of no
      corticosteroid usage (89% and 75%) as compared with the other two (32% and 50%).
      Black, Hispanic, and poor women were more likely to receive care at the hospitals
      where the rates of corticosteroid utilization were lower. Factors in the
      multivariate model included: < 1 or 1 day of hospitalization, vs. delivery on >
      or = 2 days of hospitalization (21.4: 14.5, 97.2; 4.7: 3.2, 6.9); gestational age
      < 26 weeks (2.7: 1.8, 4.1) or > 28 weeks (1.8: 1.3, 2.6) vs. 26-28 weeks; < 12
      hours of labor vs. > 12 hours (1.7: 1.2, 2.4); delivering at hospital 2, 3, 4 vs.
      hospital 1 (1.6: 1.1, 2.5; 24.3: 13.6, 43.4; 10.2: 6.8, 15.3). We conclude that
      variations in hospital practice limit widespread use of this important antenatal
      treatment.

PMID- 9642612
TI  - Does labetalol predispose to pulmonary edema in severe pregnancy-induced
      hypertensive disease?
AB  - We investigated whether use of labetalol, a beta adrenoreceptor blocking
      antihypertensive agent commonly employed as an alternative to hydralazine, is
      independently associated with pulmonary edema in women with severe preeclampsia.
      We retrospectively evaluated women with severe preeclampsia who were given
      labetalol by intravenous bolus for MAP > 120 mm Hg. Outcome variables included:
      achieving MAP < 120 mm Hg with < 300 mg of labetalol, incidence of adverse
      effects of the drug, including pulmonary edema, hypotension, and maternal
      bradycardia. Total intravenous fluid intake exceeding output (+ delta I/O) and
      presence or absence of preeclamptic liver involvement were noted. Statistical
      analysis included unpaired t-tests and Fisher's exact test. Fifty-one women were
      studied, 7 (13.7%) of whom developed pulmonary edema. Demographic and pregnancy
      characteristics were not different between patients who did or did not develop
      pulmonary edema. No patient had detectable underlying heart disease. Patients
      with or without pulmonary edema did not differ as regards entry MAP (130 +/- 14
      vs. 129 +/- 18 mm Hg), total dose of labetalol (209 +/- 83 vs. 193 +/- 39 mg/24
      hours), incidence of bradycardia or hypotension (0/7 vs. 8/44), or presence of
      hepatic involvement (1/7 vs. 9/44). However, there was a significant difference
      in degree of positive fluid balance. Patients developing pulmonary edema had a
      net gain of 1,466 +/- 429 mL of fluid in the 24 hours in which they received
      labetalol than those who did not (659 +/- 1152 mL, P = .003). Initial central
      hemodynamic monitoring data revealed no impairment of cardiac performance (mean
      cardiac output 7.7 +/- 1.8 L/min, cardiac index 4.0 +/- 0.8 L/min/m2, left
      ventricular stroke work index 73 +/- 9 g.m.m-2) despite high pulmonary capillary
      wedge pressures (22 +/- 4 mm Hg). We conclude that the incidence of pulmonary
      edema in patients with severe preeclampsia who are treated with labetalol appears
      to be a result of an increase in third space fluid accumulation as a
      manifestation of the severity of their disease, not a direct effect of the drug
      on cardiac performance.

PMID- 9642613
TI  - Delayed appearance of pulmonary maturation markers is associated with poor
      glucose control in diabetic pregnancies.
AB  - Fetuses born after pregnancies complicated by diabetes display delayed pulmonary
      maturation as measured by the delayed appearance of biochemical indicators of
      pulmonary maturity (phosphatidylglycerol, lecithin/sphingomyelin ratio) and by
      the occurrence of hyaline membrane disease even in term gestations. We tested the
      hypothesis that poor maternal glycemic control is associated with delayed
      appearance of the biochemical markers of fetal pulmonary maturation. Consecutive
      diabetic pregnancies with documentation of maternal glycemic control and amniotic
      fluid analysis for PG were analyzed. Maternal glycemic control was defined as
      good if the mean blood glucose was < or = 5.8 mmol/L (105 mg/dl) and poor if >
      5.8 mmol/L. The presence of amniotic fluid phosphatidylglycerol was considered an
      indicator of lung maturity. Hyaline membrane disease was defined by the criteria
      of Corbet et al. [J Pediatr 118:277-284, 1991]. A total of 621 diabetic
      pregnancies were analyzed (261 good glycemic control, 360 poor glycemic control).
      Phosphatidylglycerol was absent in 21% of good glycemic control vs. 31% of poor
      glycemic control pregnancies (P < 0.05). When stratified by gestational age, the
      risk of absence of phosphatidylglycerol was significantly higher in the poor
      glycemic control group (O.R. 1.83, 1.19-2.84). At 36-37.9 weeks, poor glycemic
      control pregnancies had significantly higher rates of absent phosphatidylglycerol
      (37% vs. 22%, O.R. 2.04, 1.1-3.9). All cases of hyaline membrane disease beyond
      32 weeks gestation occurred in poor glycemic control pregnancies. There were no
      cases of hyaline membrane disease beyond 37.0 weeks gestation. We conclude that
      poorly controlled maternal glucose levels are associated with delayed appearance
      of phosphatidylglycerol in diabetic pregnancies. However, after 37.0 weeks of
      gestation, no significant neonatal pulmonary disease occurred.

PMID- 9642615
TI  - Effects of smoking, alcohol, and drugs of abuse on the outcome of "expectantly"
      managed cases of preterm premature rupture of membranes.
AB  - We evaluated the outcome of pregnancies complicated by preterm premature rupture
      of membrane (PROM) in order to determine if tobacco, alcohol, or illicit drug
      usage were associated with alterations in pregnancy or neonatal outcome.
      Comparisons in outcome were made with respect to tobacco, alcohol, and/or illicit
      drug usage. Comparisons were made with gestational age (GA) of PROM, GA of
      delivery, latency period (LP), maternal age, initial cervical exam (by speculum),
      age, race, tocolytic use, chorioamnionitis, and birthweight. Student's t-test,
      Mann-Whitney test, and Chi-square analysis were used to evaluate for significant
      differences (significance set at P < 0.05). A total of 119 charts were evaluated.
      Differences were noted with respect to smokers vs. nonsmokers for latency period
      (6.0 days vs. 9.4 days, P < 0.03), age (29.1 years vs. 24.8, P < 0.001), and
      gravidity (4.2 vs. 2.8, P < 0.005). Differences were noted for use of alcohol and
      age (29.9 vs. 25.2, P < 0.006). Differences were also noted for the use of
      illicit drugs and the following variables: age (30.0 vs. 24.9, P < 0.001),
      gravidity (4.7 vs. 2.5, P < 0.006), latency (6.2 vs. 9.0, P < 0.009), and parity
      (2.6 vs. 1.2, P < 0.01). A difference was noted with respect to cocaine and
      latency period (5.8 vs. 9.0, P < 0.01), age (31.2 vs. 24.8, P < 0.001), gravidity
      (4.8 vs. 2.9, P < 0.01), and parity (2.6 vs. 1.2, P < 0.03), and the use of
      tocolytics (22% vs. 55.4%, P < 0.02). These relationships held after multivariate
      analysis was performed. There were no associations among use of tobacco, alcohol,
      drugs of abuse, or cocaine and respiratory distress syndrome, intraventricular
      hemorrhage, or necrotizing enterocolitis. The use of tobacco during pregnancy
      appears to shorten the latency period in pregnancies complicated by PROM. Cocaine
      abuse also appears to shorten the latency period. These shortened latency periods
      could potentially contribute to increased neonatal morbidity. Larger studies
      evaluating this are needed.

PMID- 9642614
TI  - Pregnancy complicated by autoimmune polyglandular syndrome type II: a case
      report.
AB  - Autoimmune polyglandular syndrome may complicate pregnancy and be confused with
      hyperemesis gravidarum as a cause of hypoglycemia and electrolyte imbalance in
      the first trimester of pregnancy. Autoimmune polyglandular syndromes are uncommon
      disorders characterized by the development and presentation of multiple endocrine
      and organ dysfunction. To our knowledge, we present the first case of an
      autoimmune polyglandular syndrome complicating pregnancy. A 26-year-old woman,
      gravida 5 para 3 at 12 weeks gestation, presented with hyperemesis and signs and
      symptoms consistent with adrenal insufficiency and hypothyroidism. Evaluation
      revealed autoimmune polyglandular syndrome type II. Autoimmune polyglandular
      syndromes are a myriad group of diseases characterized by polyglandular
      dysfunction. These syndromes should be kept in mind when dealing with pregnant
      patients presenting with hyperemesis and an electrolyte imbalance who do not
      improve with the usual treatment for hyperemesis. An endocrine dysfunction such
      as polyglandular syndrome may exist.

PMID- 9642616
TI  - Blood-brain barrier disruption for the treatment of malignant brain tumors: The
      National Program.
AB  - Chemotherapy delivery for the treatment of malignant brain tumors is markedly
      enhanced when given in conjunction with osmotic opening of the blood-brain
      barrier. Osmotic opening or disruption of the blood-brain barrier is achieved
      while the patient is under general anesthesia, by the infusion of mannitol into
      the internal carotid or vertebral artery circulation. The mannitol infusion is
      followed by administration of intraarterial chemotherapy. A National Blood-Brain
      Barrier Program now exists and includes six universities. Within the National
      Program over 4200 blood-brain barrier disruption procedures have been performed
      in over 400 patients. Patients with primary central nervous system (CNS)
      lymphoma, glioma, primitive neuroectodermal tumor (PNET), germ cell and
      metastatic cancer are eligible for treatment. Results in patients with primary
      CNS lymphoma, recently reported in the Cancer Journal, include the first example
      of a durable response in a primary brain tumor without loss of cognitive function
      and without use of radiotherapy. Results with PNET and germ cell tumors are also
      very encouraging. Advanced practice nurses coordinate the care of blood-brain
      barrier disruption patients. Care includes patients selection, education, close
      neurological observation, maintenance of fluid and electrolyte balance and
      managing effects of high-dose chemotherapy. Both acute and long-term medical and
      psychological follow-up are an essential component of the program, as well as
      patient and family support.

PMID- 9642617
TI  - Pulmonary management following acute SCI.
AB  - Pulmonary complications are the major contributor to mortality and morbidity
      following spinal cord injury (SCI), especially during the first year. Patients
      who are at increased risk of pulmonary complications include SCI individuals with
      cervical and high thoracic injuries, patients with unstable injuries who must be
      immobilized, patients with multiple injuries and individuals over the age of 65
      years. Although research exists on many of the elements of pulmonary hygiene,
      there is a paucity of systematic research linking therapeutic interventions with
      patients outcomes during the acute phase following SCI. This area is rich for the
      development of collaborative empirical studies which contribute to the science of
      preventing pulmonary complications following acute SCI. Research is needed which
      tests specific pulmonary hygiene protocols in relation to patient outcomes during
      the acute phase of SCI and in the early months after the patient returns home.

PMID- 9642618
TI  - Spinal cervical infection: a case report and current update.
AB  - Cervical spine infection is a term used to encompass osteomyelitis, discitis and
      epidural abscess. Most cases are caused by Staphylococcus aureus but other
      organisms have been isolated. The most frequent source is hematogenous spread
      from a nearby or distant source. Diagnosis is often confusing. The most common
      symptom is worsening back or neck pain that increases with movement. Patients may
      have motor or sensory changes if there is compression of the nerve roots or
      spinal cord. If the condition is not treated promptly, it may progress to
      irreversible neurologic deficit. Positive blood cultures and an elevated
      erythrocyte sedimentation rate (ESR) may be seen. Radiologic findings may include
      a paravertebral swelling, a destruction of the vertebral end plates and adjacent
      portions of the bodies and disc space and the presence of an epidural mass.
      Treatment includes radical surgical intervention for debridement and
      decompression to stabilize the spine in conjunction with 8-12 weeks of
      intravenous antibiotics. Closed continuous local antibiotic irrigation with a
      gravity control outflow system has been used.

PMID- 9642619
TI  - Elements of empowerment and MS patients.
AB  - Elements of empowerment are: cognitive, experiential, ethical, social,
      biophysiological, functional and economic. Empirical data from 64 Finnish
      multiple sclerosis patients were collected. Based on the data, the social element
      is the most dominating element of empowerment. Patient-center research in nursing
      care of MS patients should be done to facilitate MS patients abilities toward
      empowerment.

PMID- 9642620
TI  - Issues related to caring for infants to adults on an integrated epilepsy unit.
AB  - We integrated the care of patients of all ages (ranging thus far from 4 weeks to
      73 years) in our dedicated 8-bed Epilepsy Unit. Administrative issues pertaining
      to admission and discharge criteria, unit policies and procedures and an
      interdisciplinary quality assurance plan were examined in relation to the impact
      of combining both pediatric and adult patients. Clinical considerations included
      the diversified abilities needed to care for pediatric and adult patients both in
      relation to the technical skills as well as psychosocial skills required. The
      advantages of integrating patients of all ages on one unit include having a staff
      highly trained in assessment and intervention skills for a particular disorder.
      The psychosocial issues that arise in these patients, regardless of age, tend to
      encompass the entire family; therefore a holistic approach is appropriate for
      both children and adults. An autonomous nursing practice was established with the
      development of critical pathways and patient care protocols. Our experience
      suggests that integrated specialized units can enhance the care of patients with
      intractable seizures.

PMID- 9642621
TI  - Postcomatose unawareness in a brain-injured population.
AB  - Different states of unawareness are present following a coma in the brain-injured
      population. An attempt to answer three questions is made based on a review of the
      literature and multiple case studies: Which type of sensory and motor stimulation
      can be suggested? Which instruments can be used to measure behaviors and what are
      their benefits and limitation? Does learning theory help explain the postcomatose
      unawareness experience? The theoretical paradigm strongly suggests employing
      learning theory to target a precise behavior to unmask learning potential and to
      use known remediation mechanisms such as errorless learning or implicit learning.
      Speculations in the area of unmasking potential are available; these require
      intervention to target specific function that could be lost with nonuse.

PMID- 9642622
TI  - Copolymer-1 in the treatment of multiple sclerosis.
AB  - Recent research in the treatment of multiple sclerosis (MS) has yielded new
      therapies. Specifically, copolymer-1, a mixture of synthetic polypeptides
      composed of four amino acids has been effective in reducing relapse rates and
      disability in patients with relapsing-remitting MS. In a two-year multicenter,
      randomized, double-blind, placebo-controlled trial of 251 patients, copolymer-1
      was shown to reduce relapses by an average of 29% when compared with placebo.
      Sustained disability was also slightly reduced in the copolymer-1-treated group.
      The results of the clinical trial indicate that copolymer-1 positively alters the
      course of relapsing-remitting MS. With the present availability of copolymer-1,
      nurses are challenged to maintain current knowledge of nursing implications,
      interventions, patient education and goals for treatment.

PMID- 9642623
TI  - Androgen insensitivity syndrome in the era of molecular genetics and the
      Internet: a point of view.
AB  - The era of molecular genetics has seen the discovery of a great deal of
      scientific information about the androgen receptor (AR) and about the many AR
      mutations that have been identified in patients with Androgen Insensitivity
      Syndrome (AIS). In families with well-characterised mutations, carriers can now
      be identified and prenatal testing can be offered. An unexpected finding is that
      an AR mutation also causes X-linked spinobulbar muscular atrophy. The intersex
      community has established two influential support groups, the AIS Support Group
      (which has branches in the UK, North America and Australia) and the Intersex
      Society of North America (ISNA). It is ironic that at a time when advances in
      biomedical science regarding AIS are a source of pride, these support groups are
      accusing the medical profession of having ignored the real needs of patients with
      AIS. Since the support groups are willing to assist the medical profession to
      develop better approaches to the management of intersex disorders, a
      collaborative approach is likely to be mutually beneficial for patients and
      physicians. ISNA has alienated many doctors by advocating a radical approach,
      namely that surgery should not be performed to 'correct' ambiguous genitalia
      until the individual is old enough to express a gender preference. Many children
      born in developing countries have either no genital surgery to correct ambiguity,
      or surgery is carried out very late. Long term outcome studies, carried out in
      developing countries and sensitive to the cultural background, would provide
      information on how non-Western societies can accept genital abnormalities that
      would be considered unacceptable in the West.

PMID- 9642624
TI  - Animal models of type I (insulin-dependent) diabetes mellitus.
AB  - Much of our present knowledge concerning the etiopathogenesis, treatment and
      prevention of human diabetes would never have been acquired without the study of
      animal models of diabetes. The main models of IDDM may be divided into two
      groups: induced (through pancreatectomy, chemicals such as alloxan and
      streptozotocin, viruses and others) and spontaneous (mainly using BB rats and NOD
      mice). The latter, at different ages, develop a diabetic syndrome, with clinical
      characteristics, genetics and immunology that are very similar to the human
      disease. Among the more significant differences are lymphopenia (in BB rats) and
      the predominance of diabetes in females (in NOD mice). Studies aimed at
      preventing IDDM have advanced by leaps and bounds by using the two spontaneous
      models. These include various methods such as genomic modification, an influence
      over some environmental agents, immunosuppression, immunotherapy,
      immunomodulation and tolerance induction as well as protection of the beta-cell
      from autoimmune attack. The conclusions drawn from animal experiments have
      allowed some human trials to be carried out with encouraging results.

PMID- 9642625
TI  - Anticardiolipin antibodies in first-degree relatives of type 1, insulin
      dependent, diabetic patients.
AB  - First-degree relatives (FDRs) of diabetic patients are at risk of IDDM, and
      frequently present several autoantibodies. We detected anticardiolipin antibodies
      (aCL) in 42 FDRs, aged 12.4 +/- 4.2 years and in 52 controls. aCL (IgG and IgM)
      were measured by ELISA and their results expressed in arbitrary units. All FDRs
      underwent islet cell antibodies (ICA) measurement, intravenous glucose tolerance
      test and HbA1c levels. HLA typing and HLA-DQ molecular analysis were performed in
      all FDRs. Positive levels of aCL-IgG were observed in 8/42 FDRs and no control
      subject (p = 0.04); aCL-IgM values were similar in FDRs and controls. No
      correlation was found between aCL levels and chronologic age or HbA1c levels. No
      association was observed between aCL frequency and immunologic (ICA), metabolic
      or genetic (HLA) parameters. No FDR showed any feature of antiphospholipid
      syndrome. aCL-IgG presence in FDRs is suggestive of a need to carry out a follow
      up study to establish the significance of these antibodies.

PMID- 9642626
TI  - Insulin secretion and insulin resistance determined by euglycemic clamp.
AB  - Obesity among children is increasingly recognized and linked to several metabolic
      problems. In this study, 47 children, aged 5-14 yr, with exogenous obesity were
      compared to 20 normal (non-obese) children to show alterations in glucose
      metabolism. All the obese children had body mass index > 95th percentile and
      weight for age > 120%. Basal and stimulated insulin and C-peptide levels were
      obtained during oral glucose tolerance test (OGTT). Seven children from the obese
      group had impaired OGTT according to WHO criteria. Mean fasting insulin levels
      were 26.7 +/- 14.6 microIU/ml in obese and 10.99 +/- 4.36 microIU/ml in controls;
      postprandial insulin levels were 70.4 +/- 56.4 microIU/ml and 22.23 +/- 6.55
      microIU/ml, respectively (p < 0.001). The euglycemic glucose clamp technique was
      applied to 8 normal and 22 obese children. The amount of metabolized glucose (M)
      during clamp test is measured to identify glucose sensitivity. Mean M values were
      3.24 +/- 1.35 mg/kg/min in obese and 6.525 +/- 0.770 mg/kg/min in control
      children (p < 0.001). As a result of this study, it seems reasonable to consider
      all obese children and adults as being at risk for hyperinsulinism and insulin
      resistance.

PMID- 9642627
TI  - Unusual magnetic resonance imaging findings of the sellar region in subjects with
      hypopituitarism: report of 4 cases.
AB  - Out of 323 consecutive growth hormone deficient patients who underwent magnetic
      resonance imaging (MRI), we describe the clinical and neuroradiological
      characteristics of four patients in whom MRI revealed unusual pictures of the
      sellar area. They were selected as unique in their morphological picture and
      representative of rare conditions. At presentation all subjects had short
      stature, growth hormone (GH) deficiency and complex phenotypical abnormalities.
      Patient 1. Female affected by vaginal atresia and sinus urogenitalis, polydactyly
      and syndactyly with Y-shaped metacarpals. MRI at age 11.2 years revealed normal
      pituitary, but hypothalamic mass occupying the suprasellar and interpeduncular
      cistern. The diagnosis of Hall-Pallister syndrome was made. Patients 2 and 3. Two
      sisters with a history of epilepsy both showing mild intellectual deficiency,
      midface hypoplasia and ectodermal dysplasia. MRI at age 8 and 12 years
      respectively displayed in both cases a round hypointensity protruding from the
      dorsum sellae into a normal pituitary. The diagnosis was sellar spine. Patient 4.
      Male with a history of postnatal hypoglycemia showing microphallus and clinical
      features of severe hypopituitarism. Hormonal evaluation at age 8 months confirmed
      multiple pituitary hormone deficiencies and MRI at age 6 years showed absent
      anterior lobe, rudimentary stalk and posterior lobe ectopia. The diagnosis was
      pituitary aplasia. The patients described show that MRI in pituitary dwarfs can
      reveal unusual intrasellar findings and allow the correct diagnosis of rare
      syndromes. Our patients also demonstrate the wide variability in the association
      of hypopituitarism with midline congenital abnormalities and the possible
      combination with complex syndromes.

PMID- 9642628
TI  - Growth hormone deficient children treated from before two years old fail to catch
      up completely within five years of therapy.
AB  - We retrospectively investigated growth response to therapy of 12 patients with
      idiopathic growth hormone deficiency (GHD), who received GH (0.6-0.7 IU/kg/week)
      in daily subcutaneous injections from before 2 years of age and for a period of
      60 months, in order to ascertain whether very early treatment can enable GHD
      children to catch-up quickly and completely their initial height deficiency. The
      onset of therapy was followed in all patients during the 1st year by a
      significant growth spurt, which persisted, even though attenuated, during the
      following 4 years. Height deficiency for chronological age (CA) significantly and
      progressively decreased during the entire study period (from -3.7 +/- 1.9 to -1.0
      +/- 1.0 SDS, p < 0.0025), with a cumulative height gain of 2.7 +/- 1.6 SDS. In
      spite of this catch-up growth no patient attained the target percentile by the
      5th year of therapy and their average height (CA) was still lower with respect to
      the average target height (TH) at the last check-up. Because of the significant
      bone age (BA) delay still persisting in most patients, a further and complete
      catch-up growth is likely to occur during the next years of treatment, as
      suggested by the finding that average height (BA) at the last examination was
      higher than average TH. It is concluded that: a) in spite of modern therapeutical
      schedules with daily GH injections and frequent adjustments of doses, GHD
      children, even though treated from before two years of age, fail to catch-up
      completely their initial height deficiency, at least by the 5th year of therapy;
      b) a more prolonged treatment is probably needed to allow them to attain their
      target percentile. This emphasizes the importance of both early diagnosis and
      long-lasting treatment.

PMID- 9642629
TI  - Final height in long-term primary hypothyroid children.
AB  - OBJECTIVE: We studied retrospectively the statural growth and bone maturation of
      32 children with primary hypothyroidism in order to relate their final heights to
      their chronological ages, height deficits and bone ages at the beginning of
      treatment. Patients were grouped according to age when treatment was started:
      Group 1 (G1) (n = 17): (15 girls, 1 boy) 3.09 +/- 0.8 yr; Group 2 (G2) (n = 9):
      (7 girls, 2 boys) 9.1 +/- 1.2 yr, and Group 3 (G3) (n = 6): (5 girls, 1 boy)
      13.58 +/- 1.13 yr. At diagnosis G1 and G2 were prepubertal and G3 children were
      in puberty. In 10 patients of G1, 7 of G2 and 6 (all) of G3 final height was
      compared with target height. RESULTS: (SDS) Initial height: G1: -3.74 +/- 1.2;
      G2: -3.94 +/- 1.32; G3 -3.65 +/- 1. Height at onset of puberty: G1: -1.06 +/-
      1.1; G2: -2.5 +/- 1.4. Height menarche stage 5: G1: -0.63 +/- 1.1; G2: -1.76 +/-
      1.2; G3: -2.6 +/- 1.7. Final height: (whole group) G1: -0.85 +/- 0.91; G2: -1.6
      +/- 1.3; G3: -2 +/- 1.5. Final height G1 (n = 10): -1.05 +/- 0.89; G2 (n = 7) 1.2
      +/- 1. Target height G1 (n = 10): -1.22 +/- 0.78; G2 (n = 7): -0.8 +/- 1.2; G3 (n
      = 6): -1.07 +/- 1.5. Initial bone age: G1: -4.9 +/- 0.85; G2: -7.2 +/- 2.6; G3: 
      4.5 +/- 1.9. Bone age (onset of puberty) G1: -0.26 +/- 1.74; G2: -2 +/- 1.7; Bone
      age (menarche) G1: 0.09 +/- 0.6; G2: -0.5 +/- 0.6; G3: -0.76 +/- 0.82.
      CONCLUSION: G1 and G2, prepubertal at diagnosis, reached a normal adult height
      with respect to target height; G3 did not, the difference being statistically
      significant (p < 0.04). Puberty plays a decisive role in the incomplete catch-up
      growth of longstanding hypothyroid patients.

PMID- 9642630
TI  - Patients with Hashimoto's disease treated with L-thyroxine and followed for three
      years.
AB  - This study investigated the effectiveness of L-thyroxine management in 32
      patients (mean age 11 years and 2 months; M:F = 1:5) with Hashimoto's disease
      followed annually for 3 years. One (8%) of the 12 patients, euthyroid at the
      onset, never required treatment; of the four (33%) who began treatment
      immediately, two were able to stop at the 1st or 2nd follow-up, whereas two had
      to continue. The other seven (59%) who did not begin treatment immediately had to
      start at the 1st, 2nd or 3rd follow-up. The findings in this small series suggest
      that hormone management may prove effective to a certain extent in euthyroid
      Hashimoto patients, primarily as a means of prevention.

PMID- 9642631
TI  - Onset of obesity in children through the recall of parents: relationship to
      parental obesity and life events.
AB  - Obesity is a multifactorial disease due to the influence of both genetic and
      environmental factors. Parents of 886 obese patients (427 boys and 459 girls,
      aged 1-18 years) were investigated by means of a questionnaire in order to study
      the factors associated with the onset of obesity in children and the relationship
      to genetic background. At presentation obese patients had a very high mean ideal
      body weight percent (IBW%) (154 +/- 19%, median 152%, range 120-246). A
      significantly higher mean IBW% was found in children of obese parents (one obese
      parent: 158 +/- 21%, median 156%, range 120-246; two obese parents 160 +/- 18%,
      median 158%, range 123-226) in comparison to children of normal weight parents
      (150 +/- 18%; median 147%, range 120-235; p = 0.0001 for children of one or two
      obese parents versus children of normal weight parents). Parents of 414 subjects
      (46.7%) (Group A) answered that obesity had always been present. The remaining
      472 parents (53.3%) (Group B) stated that obesity had had a beginning at a mean
      age of 5.3 +/- 2.6 years (median 5.0 years, range 1.0-17.0). No difference was
      found in age at presentation, sex distribution, birth weight and number of obese
      parents between the two groups. Parents in Group B recalled an event associated
      with obesity onset in 197 cases (health event: 119 answers, psycho-social event:
      78 answers). Genetic background did not influence this pattern of feedback. In
      conclusion, parents of obese subjects seek medical advice when obesity is severe.
      Pediatricians should exert strict surveillance on weight from a very young age.
      The recall in 22% patients of health or psychosocial events at the onset of
      obesity emphasizes that medical counselling is important when the occurrence of
      particular events in life may cause erroneous eating habits.

PMID- 9642632
TI  - Normal growth in a patient with septo-optic dysplasia despite both growth hormone
      and IGF-I deficiency.
AB  - A 17 year-old female with septo-optic dysplasia (SOD) and hypopituitarism who has
      grown normally despite GH deficiency is presented. Her serum was examined to test
      current hypotheses to explain the phenomenon of growth without GH. The patient's
      serum possessed potent in vitro growth-promoting activity (GPA) in an erythroid
      progenitor-cell clonal proliferation assay consistent with the patient's normal
      growth performance. In contrast to previously reported cases of growth without
      GH, total IGF-I concentrations were very low in this patient, precluding IGF-I
      being responsible for the observed GPA and normal growth pattern. Furthermore,
      circulating free IGF-I was also low which is reported for the first time in such
      a case. A detailed picture of IGF-binding proteins is also presented. To test the
      hypothesis that hyperinsulinemia might be responsible for the observed GPA, in
      vitro GPA experiments were performed before and after removal of insulin by
      immunodepletion. Neither partial nor complete removal of insulin abolished the in
      vitro cell proliferation response. These data demonstrate that neither IGF-I nor
      insulin is the factor responsible for GPA in at least this patient with SOD and
      growth without GH.

PMID- 9642633
TI  - Secondary central precocious puberty in a girl with McCune-Albright syndrome
      responds to treatment with GnRH analogue.
AB  - GnRH analogues have been used with variable success for the treatment of
      precocious puberty in children with McCune-Albright syndrome (MAS). In general,
      children with a bone age of less than 13.5 yr have been reported not to have
      benefitted from GnRH therapy. In contrast, we have successfully treated a young
      girl with MAS and--probably secondary--central precocious puberty using
      Decapeptyl, a long acting GnRH analogue. The girl with MAS presented at the age
      of six years with cafe au lait spots, osseous lesions and precocious puberty. At
      initial presentation height was 130.7 cm (> 97 percentile), weight 27.5 kg (> 97
      percentile), Tanner stage B3, PH3. Bone age was 11 yr. Magnetic resonance imaging
      of the brain was normal. Endocrine function tests were normal with the exception
      of biochemical evidence of central precocious puberty: LHRH test: LH 0.9/20.3,
      FSH 4.3/12.7 (mU/ml), E2 15.6 pg/ml. Therapy was started with 3.75 mg GnRH
      analogue i.m. every four weeks and was intensified two years after the beginning
      of therapy to 3.75 mg i.m. every three weeks. Three years after the start of
      treatment bone age was 12 yr and growth velocity was 2.5 cm/year. Tanner stage
      was B3, PH3 and LHRH testing revealed biochemical evidence for suppression of
      gonadotropins: LH < 0.5/1.0, FSH 1.9/2.5 (mU/ml). We hypothesize that a subgroup
      of patients with MAS might present with a central form of precocious puberty.
      This may be particularly so in children with a bone age greater than or equal to
      11 yr. Central precocious puberty in these children might follow extensive sex
      steroid exposure due to the peripheral precocious puberty induced by the
      activating mutation of the Gs protein gene. This central form of precocious
      puberty responds to therapy with GnRH analogues.

PMID- 9642635
TI  - Re: Growth hormone treatment without a needle.

PMID- 9642634
TI  - Primary hyperparathyroidism in children: patient report and review of the
      literature.
AB  - Although primary hyperparathyroidism has rarely been described in pediatric
      patients, prompt diagnosis can avoid severe CNS and metabolic consequences. The
      aim of this paper is to report a 6 year-old girl whose first symptoms began at
      eight days of age with cyanosis, hypotonia, and upward gaze deviation. At 4
      months, she was admitted due to neurologic disorders and recurrent infection, but
      the definite diagnosis was made only six years later. Her serum calcium levels
      are among the highest ever reported in the medical literature, reaching 25.5
      mg/dl (6.36 mmol/l). Hypercalcemia, very high levels of parathormone (1550 ng/l-
      normal range 10-65) and bone deformities posed no problem to diagnosis when she
      first came to our attention. Nephrocalcinosis and impaired renal function were
      detected and this child had to be treated with diuretics (furosemide) and
      hydration that were able to lower her serum calcium levels. Imaging studies
      including 99mTc-sestamibi scan were not diagnostic. At surgery, the four
      parathyroid glands were mildly enlarged, with primary hyperplasia. The four
      glands were removed, cryopreserved, and 14 fragments (1 mm each) were
      autotransplanted to the braquioradial muscle of the left forearm. After a first
      phase of hypocalcemia (hungry-bone syndrome), treated with calcium and
      calcitriol, the calcium levels stabilized. The question is whether she will
      experience some degree of recovery from her neurological problems, since her
      severely high calcium levels have been maintained for such a long time.

PMID- 9642636
TI  - The molecular genetics of endocrine tumours.
AB  - The molecular genetics of endocrine tumours is an area of great interest, due to
      the heterogeneity of endocrine tumour types, the association of hormone over
      production in some cases, and the wide variation in tumour behaviour. Genes
      implicated fall into functional categories such as oncogenes, in which mutations
      tend to cause activation, and tumour suppressor genes, in which mutations lead to
      loss of function. Oncogenes include the receptor tyrosine kinases such as RET,
      signal transduction proteins and other molecules such as cell cycle regulators
      and nuclear proteins. Tumour suppressor genes include cell cycle regulators such
      as p53 and other molecules such as the MEN 1 gene. Loss of heterozygosity studies
      help in the initial localisation of the latter. Endocrine tumours, as with other
      tumours, develop as a result of a combination of genetic events, and in the
      paediatric age group they often occur in the setting of familial cancer
      syndromes. In this review we analyse the main genetic lesions which have been
      described in endocrine tumours. There has been an explosion of knowledge in the
      last 5 years including the identification of the causative genes for MEN 2 and
      most recently for MEN 1. Characterisation of such genes also aids in the study of
      somatic mutations in sporadic versions of the same tumour types as occur in the
      familial syndromes. Identification of a genetic predisposition to a certain
      tumour has management implications that are still to be clarified in most cases,
      although in the case of MEN 2 the guidelines for prophylactic thyroidectomy are
      generally well accepted.

PMID- 9642637
TI  - Frequency and characteristics of lingual thyroid not detected by screening.
AB  - Four patients with lingual thyroid glands presenting beyond the neonatal period
      have been evaluated at the Hospital for Sick Children, Toronto since the advent
      of neonatal TSH screening. All were female, clinically euthyroid at diagnosis and
      presented with symptoms of a lingual mass. We estimate that 1.6% of lingual
      thyroids are missed by this TSH based thyroid screening program and approximately
      1/600,000 live births present in childhood or adolescence with a lingual thyroid.
      Physicians should still include lingual thyroid in the differential diagnosis of
      a mass at the base of the tongue.

PMID- 9642638
TI  - Thyroxine screening values in premature infants.
AB  - OBJECTIVES: Premature infants often have low thyroxine levels when compared to
      fullterm infants. We sought to determine gestational age specific normal ranges
      for thyroxine screening results for premature infants in neonatal intensive care
      units. METHODS: Thyroid screening results for infants less than 38 weeks
      gestation admitted to two NICUs were examined. For each sample the thyroxine Z
      score was computed using parameters from fullterm infants. The mean thyroxine Z
      score was calculated for each gestational age for days of life 1, 2, 3-7, 8-14,
      15-21, 22-28, and 29-60. RESULTS: There were 1144 specimens obtained from 543
      premature infants. The mean thyroxine Z-score was below 0 for almost every
      gestational age and days-of-life category. The mean thyroxine Z-score increased
      with gestational age, but did not rise with increasing postpartum age.
      CONCLUSION: The data show that normal thyroxine Z-scores for premature infants
      are lower than for fullterm infants and remain low at least as long as the
      infants remain ill.

PMID- 9642639
TI  - The association of congenital hypothyroidism and congenital gastrointestinal
      anomalies in Down's syndrome infants.
AB  - OBJECTIVE: To study the prevalence of congenital hypothyroidism in infants with
      Down's syndrome and to verify whether there is an association with other
      congenital defects. METHODS: This is a prospective study of 112 Down patients,
      less than 1 year of age, who attended Songklanagarind Hospital from January 1991
      to December 1996. Free T4 and TSH determinations were performed in all Down
      infants. Information on karyotype, sex, maternal age and other congenital
      anomalies was collected. RESULTS: Congenital hypothyroidism was detected in 17
      patients (15.2%); 3 overt congenital hypothyroidism; 6 persistent compensated
      hypothyroidism; and 8 transient compensated hypothyroidism. Nine of the 20
      patients (45%) with congenital gastrointestinal anomalies had congenital
      hypothyroidism, while 8 out of 92 patients (8.7%) without congenital
      gastrointestinal anomalies had congenital hypothyroidism. The odds ratio was 8.59
      (95% confidence interval 2.4-31.6; p = 0.0001). CONCLUSION: Congenital
      hypothyroidism has a relatively high prevalence rate in Down infants and tends to
      occur in Down patients with gastrointestinal anomalies.

PMID- 9642640
TI  - Growth stunting in early life in relation to the onset of the childhood component
      of growth.
AB  - AIMS: Growth stunting is prevalent in developing countries. The prevalence of
      stunting ranges from 10-80% or more. The critical period for growth faltering in
      length is between six and 18 months. The aims of this study were 1) to
      investigate the association between the age at onset of the childhood component
      and growth stunting in early life; 2) to develop a screening method for
      identifying any individual infant subject to stunting in early life. MATERIALS &
      METHODS: This community-based longitudinal study was carried out in Lahore,
      Pakistan. Three studied areas and one local control group were included in the
      study. There were 425 subjects for whom data were available for determining the
      age at onset of the childhood component. The onset was defined as an abrupt
      increase in length velocity. It was determined individually using the infancy
      childhood-puberty growth model. RESULTS: The medians of the age at onset of
      childhood component were 15, 13, 10 and 9 months in the periurban, village, urban
      and control groups, respectively. The onset was significantly related to both
      length and length velocity during the critical period of stunting. Based on the
      distribution of individual length increment from 12 to 15 months, 2.0 and 3.0 cm
      were chosen as the cut-off points to identify a stunting infant. In the normal
      onset group, 84% of the children were identified as growing normally; in the
      delayed onset group, 61% were identified as stunting. Using this screening
      method, 97% of children have a delayed onset if their length increase is below 2
      cm from 12 to 15 months; 99% of them have a normal onset if the increase is above
      3 cm over the same period. CONCLUSIONS: The age at onset of the childhood
      component can significantly explain the variations in both length and length
      velocity in early life. The stunting screening method reported here is simple. It
      can be used in almost any situation, such as a pediatric clinic or community
      based survey.

PMID- 9642641
TI  - Pseudopapilledema and congenital disc anomalies in growth hormone deficiency.
AB  - Optic nerve hypoplasia is a congenital disc anomaly associated with growth
      hormone deficiency (GHD). Pseudotumor cerebri is an adverse event associated with
      growth hormone treatment (hGH) and manifested by increased intracranial pressure
      and papilledema. Pseudopapilledema is a generic ophthalmologic term encompassing
      several conditions, including congenital disc anomalies. It is benign and can be
      distinguished from papilledema by physical examination. The objective of this
      report is to document that congenital disc abnormalities, which can be confused
      with papilledema, occur in children with GHD. Three patients with GHD had
      fundoscopic examinations suggestive of papilledema and possibly pseudotumor
      cerebri. The abnormal optic nerves were characteristic of pseudo-papilledema, and
      appear to be a variant of optic nerve hypoplasia. The finding of optic disc
      abnormality during hGH may reflect pseudo-papilledema and not pseudotumor
      cerebri. Of equal importance, the reported patients indicate that the finding of
      pseudopapilledema in short children should suggest the possibility of GHD.

PMID- 9642642
TI  - Prevention of diabetes in non-obese diabetic (NOD) mice by short-term and high
      dose IGF-I treatment.
AB  - This report describes the results of IGF-I treatment in a NOD mouse colony with a
      high incidence of overt diabetes. The animals were treated with IGF-I 17.9
      nmol/day at 28-41 days of age and 35.9 nmol/day at 42-69 days of age and observed
      up to 280 days of age. Three of 12 (25%) IGF-I-treated animals developed diabetes
      compared with 8 of 11 (73%) controls (P < 0.05). The severity of insulitis at the
      conclusion of the follow-up was less pronounced in non-diabetic treated animals
      than in non-diabetic controls. These data support previous findings that IGF-I
      treatment protects the pancreatic beta-cells from destruction by diabetic
      autoimmunity in NOD mice.

PMID- 9642643
TI  - Thyroid abnormalities as a feature of DiGeorge syndrome: a patient report and
      review of the literature.
AB  - DiGeorge syndrome or anomaly consists of a developmental field defect which is
      characterized by congenital absence or hypoplasia of the thymus and parathyroids,
      as well as facial dysmorphism and congenital heart defects. Other congenital
      malformations may coexist, in particular, thyroid abnormalities. A case of
      congenital hypothyroidism and DiGeorge syndrome is reviewed. Necropsy, clinical,
      and experimental studies also show that thyroid abnormalities may be a feature of
      DiGeorge syndrome. Although this could be purely coincidental, our case suggests
      that thyroid gland dysgenesis may be more common than previously thought. Thus,
      children with the DiGeorge syndrome may be at higher risk for hypothyroidism.
      Because of this potential association, patients who are considered to have this
      anomaly should have early newborn thyroid screening.

PMID- 9642644
TI  - Persistent neonatal hypoglycemia: an unusual finding of congenital
      hypothyroidism.
AB  - We report a newborn infant who has congenital hypothyroidism associated with
      profound and persistent neonatal hypoglycemia. Persistent and marked hypoglycemia
      has not been previously reported in congenital hypothyroidism to our knowledge.
      The cause of this condition may be reduced glyconeogenesis or insulin clearance.

PMID- 9642645
TI  - Non-insulin dependent diabetes mellitus in a prepubertal child with Prader-Willi
      syndrome.
AB  - Diabetes mellitus has only rarely been reported in prepubertal children with
      Prader-Willi syndrome. All reported children have required insulin therapy. We
      report the development of a previously unrecognized association of non-insulin
      dependent diabetes mellitus in an obese 6 year-old child with Prader-Willi
      syndrome. She has never developed ketosis or acidosis, and she has been treated
      with oral hypoglycemic medication.

PMID- 9642646
TI  - Growth and developmental follow-up forms.

PMID- 9642647
TI  - Carbohydrates as a cerebral metabolic fuel.
AB  - The human brain is an extremely active metabolic organ with little endogenous
      stores of energy. It is thus dependent on circulating glucose to fuel metabolism
      and support cognitive functioning. However there is growing evidence that the
      human brain is able to utilise other non-glucose fuels during times of glucose
      lack. We review the evidence for the potential of the human brain to use the
      alternate fuels lactate and beta-hydroxybutyrate, and some recent studies
      examining the ability of regions of brain to use non-glucose lipid fuels. The
      human brain does not seem to have the ability to use the gluconeogenic precursor
      alanine to any significant degree. Regionality within the brain can be examined
      in vivo by the use of positron emission tomography, which offers the exciting
      prospect of studying human brain metabolism in vivo using a simple and non
      interventional technique. Increased understanding of the brain's metabolism, the
      way in which hypoglycaemia is recognised and the manner in which this can be
      altered in the syndrome of hypoglycaemia unawareness and deficient
      counterregulation will help develop further strategies to prevent the clinical
      problems associated with hypoglycaemia in insulin-dependent diabetic adults and
      children.

PMID- 9642648
TI  - Counterregulatory mechanisms to insulin-induced hypoglycemia in humans: relevance
      to the problem of intensive treatment of IDDM.
AB  - Hypoglycemia unawareness is a condition of decreased/absent perception of
      specific symptoms which normally inform the subject that plasma glucose is
      decreasing to dangerous levels resulting in neuroglycopenia. This syndrome is
      frequent in IDDM. In the absence of warning symptoms, IDDM patients cannot take
      any measure (e.g. eating) to prevent severe neuroglycopenia (unconsciousness).
      Because hypoglycemia unawareness is associated with impaired glucose
      counterregulation, especially reduced adrenaline responses, hypoglycemia
      unawareness is a risky condition for severe hypoglycemia. A number of studies in
      animals and humans indicate that hypoglycemia unawareness is largely, if not
      fully, secondary to recurrent or chronic hypoglycemia. Meticulous prevention of
      hypoglycemia in IDDM largely recovers the symptoms of hypoglycemia and the
      responses of adrenaline. It is important that diabetologists and IDDM patients
      are familiar with the syndrome of hypoglycemia unawareness and learn how to
      prevent/treat it in programs of intensive therapy. Intensive therapy aiming
      strictly at normoglycemia may increase the frequency of hypoglycemia and
      hypoglycemia unawareness. On the other hand, if intensive therapy is combined
      with a program of prevention of hypoglycemia, the percentage of HbA1c can be
      maintained long-term below 7.0% (i.e. below values risky for onset/progression of
      complications), and at the same time the frequency of hypoglycemia is very low.
      Under these conditions, IDDM patients maintain the awareness of warning symptoms
      and adrenaline response to hypoglycemia, a vital back-up system for the safety of
      intensive therapy of IDDM.

PMID- 9642649
TI  - Hypoglycemia due to hormone deficiencies.

PMID- 9642650
TI  - Ions and genes in persistent hyperinsulinaemic hypoglycaemia in infancy: a
      commentary on the implications for tailoring treatment to disease pathogenesis.

PMID- 9642651
TI  - Persistent hyperinsulinemic hypoglycemia of infancy: long-term results.
AB  - Data from 15 infants with persistent hyperinsulinemic hypoglycemia of infancy
      (PHHI), presented to our hospital from 1976 to 1995, were retrospectively
      analyzed. Nine patients were successfully managed with prolonged (1.25-13 yr)
      diazoxide therapy and frequent, low protein feeds. Three of them are still being
      treated with diazoxide, 7.75, 9.25 and 13 yr post diagnosis. Four patients were
      managed only with frequent, low protein feeds. One patient had 2/3
      pancreatectomy, and another had excision of a focal lesion which proved to be
      focal nesidioblastosis. Two patients were lost to follow up. No patient has shown
      neurological damage. One girl developed seizures at age 11.5 yr without
      hypoglycemia. The patient with 2/3 pancreatectomy developed diabetes mellitus at
      the age of 20 years. Although conservative management of PHHI is very laborious
      for the family and the physician, it should be applied as long as euglycemia is
      accomplished. Definition of the anatomical lesion (focal or diffuse) prior to
      pancreatectomy is recommended.

PMID- 9642652
TI  - Preoperative use of octreotide in a newborn with persistent hyperinsulinemic
      hypoglycemia of infancy.
AB  - In this paper, we describe a newborn diagnosed with persistent hyperinsulinemic
      hypoglycemia of infancy (PHHI) at two days of age. She presented with severe
      asymptomatic hypoglycemia and required both a high rate of glucose infusion and
      diazoxide treatment. On the 9th hospital day, due to persistent and intractable
      hypoglycemia, subcutaneous octreotide treatment was initiated. This treatment
      reduced the rate and concentration of glucose needed to be infused but the
      hypoglycemia did not subside totally. On the 18th hospital day near-total
      pancreatectomy was performed. Tachyphylaxis resulting from continuous use of
      octreotide limited its effect but enabled us to keep the patient euglycemic
      preoperatively.

PMID- 9642653
TI  - Hypoglycemia in childhood: a clinical approach.
AB  - A child with hypoglycemia presents very frequently an urgent diagnostic and
      therapeutic challenge. The main causes of hypoglycemia and the clinical approach
      and laboratory investigations are reviewed underlining that the relationship
      between the hypoglycemic event and the last meal can aid in diagnosis, in
      particular for metabolic diseases. Only a correct and precise diagnosis can allow
      adequate and appropriate treatment and prevention of future hypoglycemic events.

PMID- 9642654
TI  - Hypoglycemia during intensified insulin therapy of young children.

PMID- 9642655
TI  - Hypoglycaemia during intensified insulin therapy of children and adolescents.
AB  - Good metabolic control prevents or at least postpones late vascular
      complications, but several studies indicate that such good metabolic control
      cannot be reached without simultaneous increase in the incidence of severe
      hypoglycaemia. We have been able to reduce late complications through multiple
      insulin therapy adjusted on the basis of active self control combined with active
      psychosocial support and education. A prospective regular registration of all
      hypoglycaemic incidents in about 130 diabetic children and adolescents shows that
      in spite of reasonably good HbA1c values (mean and median 6.9%, corresponding to
      7.9% with the DCCT method), we have less incidence of severe hypoglycaemia (13-17
      per 100 patient years) than reported in other recent studies (20-25 per 100
      patient years). We saw no correlation between HbA1c and severe hypoglycaemia, but
      most hypoglycaemia was caused by mistake or reasons not related to degree of
      metabolic control. Our conclusion is that there is no inevitable relation-ship
      between low HbA1c and hypoglycaemia. Instead hypoglycaemia should be prevented
      parallel to and in the same way as we try to reach good metabolic control.

PMID- 9642656
TI  - Problems of hypoglycemia arising in children and adolescents with insulin
      dependent diabetes mellitus. The Diabetes Study Group of The Italian Society of
      Pediatric Endocrinology & Diabetes.
AB  - Hypoglycemic episodes were studied in two large populations of prepubertal (332
      subjects, aged 6-11 years) and adolescent (200 subjects, aged 12-18 years)
      diabetic children. We confirmed the majority of published data on incidence and
      causes of hypoglycemia and added some new information on the complex
      symptomatology and fear of hypoglycemia. Longer duration of IDDM induced a change
      in the symptomatology of hypoglycemia, consisting of a reduced occurrence of
      autonomic symptoms, namely tremor, and a parallel increased experience of
      neuroglycopenic symptoms, particularly drowsiness, difficulty in concentrating,
      and lack of coordination. The latter symptoms were found more frequently in
      patients with partial unawareness, more severe episodes and higher fear of
      hypoglycemia. These observations draw attention to the neuroglycopenic symptoms
      as important warning cues of hypoglycemia. We emphasized the necessity of
      observing the change in the frequency of symptoms experienced by patients, in
      particular autonomic and neuroglycopenic symptoms, in order to educate patients
      to preserve a normal awareness of hypoglycemia and prevent severe episodes.

PMID- 9642657
TI  - Hypoglycemia in children with diabetes: incidence, counterregulation and
      cognitive dysfunction.
AB  - Hypoglycemia remains a critical problem in the treatment of IDDM and often limits
      our ability to consistently achieve excellent glycemic control. Ongoing studies
      will be important to increase our understanding of the factors responsible for
      its occurrence and the impact that hypoglycemia may have, particularly for the
      brain. Significant differences have been documented between adults and children
      in the incidence of this complication of insulin therapy as well as in the
      counterregulatory hormone responses to hypoglycemia and its effects on the CNS.
      While children with diabetes still need insulin treatment, the prevention of
      hypoglycemia will be a central aim of management. This will depend on effective
      and expert diabetes education and support for the patient and his or her family
      along with better efforts to achieve more physiological insulin replacement.

PMID- 9642658
TI  - High incidence of hypoglycemic episodes with neurologic manifestations in
      children with insulin dependent diabetes mellitus.
AB  - Hypoglycemia is a serious frequent complication of insulin therapy in type 1
      diabetes. PATIENTS AND METHODS: We surveyed 139 IDDM patients. RESULTS: Forty
      four patients (32%) reported at least one severe hypoglycemic episode. All
      patients with severe hypoglycemia experienced neurological manifestations.
      Symptoms included confusion and abnormal behavior, convulsions, coma, transient
      hemiparesis and one case of permanent hemiparesis. Most episodes occurred at
      night or during morning hours. 44% of episodes were related to delayed meal or
      snack, 11% to excess insulin administration and 13% to extra physical activity.
      HbA1c was significantly lower in patients with severe hypoglycemia compared with
      diabetic controls (7.33 +/- 1.09% and 9.45 +/- 4.32%, respectively).

PMID- 9642659
TI  - Maternal fear of hypoglycemia in their children with insulin dependent diabetes
      mellitus.
AB  - A modified version of the Hypoglycemia Fear Survey (HFS) was used to measure fear
      of hypoglycemia among mothers of 46 pre-adolescent children with IDDM.
      Glycosylated hemoglobin (HbA1) levels were measured, and episodes of severe
      hypoglycemia over the previous year were recorded. The relationships between the
      child's age, disease duration, HbA1, history of hypoglycemia, and maternal
      distress concerning hypoglycemia and HFS-P scores were explored. Maternal HFS-P
      scores were also compared to those of 78 IDDM adults. There was no relationship
      between children's age, disease duration, number of severe hypoglycemic episodes
      and maternal HFS-P scores. However, mothers whose children had passed out with
      hypoglycemia had higher HFS-P scores. Correlations between mothers' responses
      concerning their children's history of hypoglycemia and HFS-P scores suggested
      that their degree of distress associated with events which occurred when their
      child was asleep, or in a social situation was related to their total HFS-P, and
      Behavior and Worry subscores. Mothers demonstrated significantly greater fear
      than did adult patients themselves. The HFS-P may be an appropriate instrument
      for examining the psychological impact of differing treatment regimens on
      families of children with IDDM.

PMID- 9642660
TI  - Advances and controversies in etiopathogenesis of type 1 (insulin-dependent)
      diabetes mellitus.
AB  - The present state of knowledge and controversies about the etiopathogenesis of
      tyep 1 diabetes can be summarized as follows: GENETICS: MHC class II genes
      (IDDM1) confer the strongest susceptibility with a hierachy DQ > DR; more than
      ten other chromosome regions (IDDM2 to IDDM13) have been identified as candidates
      for linkage with type 1 diabetes: currently, there is consensus for insulin
      (IDDM2) and a few other loci, while the remainder await confirmation.
      ENVIRONMENT: The role of milk as a trigger is debated. In fact, the protective
      effect of breast feeding is marginal, while the immune response to milk proteins
      in type 1 diabetics is very heterogeneous; moreover, the putative autoantigens
      showing sequence homology with milk proteins have been questioned. With regard to
      viruses, seasonal variations of incidence have been confirmed, although not
      uniform across countries; serological studies are controversial, while isolation
      of viruses from diabetic pancreases remains anecdotal; very interesting is the
      demonstration of enteroviral infection in pregnant mothers of future diabetic
      children, although this does not prove a causal role; a new frontier of
      investigation could be that of endogenous retroviruses acting either as
      autoimmune genes or infectious agents. AUTOIMMUNITY: GAD65, IA2 and insulin are
      at present the only established autoantigens; autoantibodies to these molecules,
      used in combination with ICA, can accurately predict type 1 diabetes; B
      lymphocytes and autoantibodies might play a pathogenetic role; autoantigen
      targets of T-lymphocytes are yet to be characterized; assays for measuring
      autoreactive T-lymphocytes require standardization; antigen-specific Th1/Th2
      relationship in type 1 diabetes remains controversial.

PMID- 9642661
TI  - Controversies on humoral immune markers of insulin-dependent diabetes mellitus.

PMID- 9642662
TI  - Epidemiology of IDDM: recent advances.

PMID- 9642663
TI  - Controversies on the prevention of insulin-dependent diabetes mellitus by
      immunomodulation: lessons from NOD mice treated with beta-1,6;1,3-D-glucan and
      rhIGF-I.

PMID- 9642664
TI  - Recommended dietary allowances (RDA) in the dietary management of children and
      adolescents with IDDM: an unfeasible target or an achievable cornerstone?
AB  - A diet in line with RDAs is seldom achieved by IDDM patients. High post-prandial
      glucose levels are often attributed to food excess rather than to inadequate
      insulin doses. Lower dietary CHO with greater fat (in particular SFA) and protein
      are progressively scheduled instead of increasing insulin units. We studied 194
      IDDM patients (1-23 yr) on a diet conforming to RDAs with a restriction of
      sucrose and without a quantitative approach and exchange lists of food for one
      year. The diet consisted of a high intake of starchy foods and vegetables and a
      restricted amount of animal products. HbA1c mean values of the year were used as
      an indicator of metabolic control. The mean daily insulin dose was 0.53 U/kg in
      patients with diabetes duration (DD) < 2 yr and 0.81 U/kg in those with DD > 2
      yr. Mean annual HbA1c was 7.1 +/- 0.9%. The prevalence of obesity was low (5.7%).
      Adolescent females were more obese than males. A dietary approach in line with
      RDA requirements, that may help prevent any complications related to an
      inappropriate diet pattern, coupled with a dynamic insulin adjustment, is the
      first-line intervention to prevent complications in IDDM patients.

PMID- 9642665
TI  - Controversies on the pathogenesis of diabetic angiopathy: which treatment for
      normotensive adolescents with microalbuminuria and type 1 diabetes?
AB  - Between 5 and 20% of children with type 1 diabetes may develop microalbuminuria
      as a sign of incipient nephropathy starting in early puberty. Permanent
      microalbuminuria has to be distinguished from intermittent and transient
      microalbuminuria with unknown prognostic relevance. A review of clinical risk
      factors, retinal examination and an ambulatory 24-h blood pressure profile are
      recommended. Non-pharmacological interventions such as the improvement of
      glycemic control, the cessation of smoking or the feasibility of a low protein
      diet should always be considered. Concerning pharmacological intervention, in
      particular ACE-inhibitors have been shown to be beneficial in adolescents with
      hypertension but may also be renoprotective in normotensive patients with
      microalbuminuria. However, long-term studies with ACE-inhibitors in normotensive
      patients have shown negligible changes in the glomerular filtration rate, which
      better reflects the renal status during treatment than changes in the albumin
      excretion rate. Nevertheless, such treatment is currently recommended also for
      normotensive adolescents if other interventions are not successful.

PMID- 9642666
TI  - Controversies on the prevention of diabetic nephropathy.
AB  - Renal function declines progressively in patients with diabetic nephropathy and
      the decline may be slowed by some preventive interventions. Optimized and
      intensive insulin therapy delays the onset and slows the progression of diabetic
      nephropathy. Moreover, dietary restriction, avoiding a high protein intake, could
      be effective in reducing glomerular hyperfiltration. Finally, there is evidence
      that angiotensin-converting enzyme inhibitors reduce renal damage by one or more
      mechanisms independent of their antihypertensive effects. Some controversial
      aspects of the prevention of diabetic kidney disease are presented and discussed.

PMID- 9642667
TI  - IDDM prevention trials in progress--a critical assessment.

PMID- 9642668
TI  - It's "all in the family": responsibility for diabetes care.
AB  - Despite its importance, diabetes management it is an area of great difficulty for
      children and adolescents. As children reach the teenage years, satisfactory
      levels of treatment adherence and glycemic control become increasingly difficult
      to obtain. In order to promote better diabetes care, the present paper emphasizes
      the need for families to remain actively involved in their youngster's diabetes
      care, regardless of the child's age. Recent studies of children and adolescents
      with diabetes are described that support the view that, even as responsibility
      for diabetes care shifts from a parent-managed to an adolescent-managed system,
      family members should remain actively involved in day to day management. Based on
      current research efforts, the specific ways that family members can remain active
      and involved are discussed.

PMID- 9642669
TI  - GYKI 52466 [1-(4-aminophenyl)-4-methoxy-7,8-methylenedioxy-5H-2,3-benzodiazepine
      hydrochloride] and the anticonvulsive activity of conventional antiepileptics
      against pentetrazol in mice.
AB  - Excitatory amino acids participate in the generation of seizure activity.
      Consequently, the effects of GYKI 52466 [1-(4-aminophenyl)-4-methoxy-7,8
      methylenedioxy-5H-2,3-benzodiazepine hydrochloride], an antagonist of glutamate
      mediated events, on the protective activity of conventional antiepileptic drugs
      against pentetrazol were studied. GYKI 52466 (up to 10 mg/kg, i.p.) did not
      affect the clonic phase of pentetrazol (injected s.c. at its CD97 of 90 mg/kg)
      convulsions. Only the antipentetrazol activity of valproate (100 mg/kg) was
      enhanced by GYKI 52466 (10 mg/kg)--the percentage of mice protected was
      significantly increased from 20 to 90%. The anticonvulsive activity of clonazepam
      (at 0.01), ethosuximide (at 50), and phenobarbital (at 2.5 mg/kg) was not
      modified by GYKI 52466 (up to 10 mg/kg). The combination of valproate (100 mg/kg)
      with GYKI 52466 (10 mg/kg) did not affect the performance of mice evaluated in
      the chimney test. However, this combination resulted in significant memory
      deficits, measured in the passive avoidance task. In no case did GYKI 52466 (10
      mg/kg) affect either total or free plasma levels of antiepileptic drugs (as
      measured by immunofluorescence), so a pharmacokinetic interaction is not
      probable. Finally, the interaction of the non-NMDA receptor antagonist with
      antiepileptic drugs does not seem promising in the pentetrazol test, recognized
      as a model of human myoclonic epilepsy.

PMID- 9642670
TI  - The effect of glutamate and inhibitors of NMDA receptors on postdenervation
      decrease of membrane potential in rat diaphragm.
AB  - The early postdenervation depolarization of rat diaphragm muscle fibers (8-10 mV
      within 3 h in vitro) is substantially smaller (3 mV) when muscles are bathed with
      1 x 10(-3) M L-glutamate (Glu) or 1 x 10(-3) M N-methyl-D-aspartate (NMDA). The
      effects of Glu and NMDA are inhibited in a dose-dependent manner by competitive
      inhibitor 2-amino-5-phosphonovaleric acid (APV) with Ki 6.3 x 10(-4) M, by 2 x
      10(-7) M MK-801, which acts as an open channel inhibitor, by 2-3 x 10(-4) Zn2+,
      which reacts with surface-located sites of the NMDA subtype of the glutamate
      receptor, and also by glycine-free solutions and 7-Cl-kynurenic acid, which
      inhibits the glycine binding sites on NMDA receptors. It follows that the effect
      of glutamate on early post-denervation depolarization is mediated by the NMDA
      subtype of glutamate receptor with similar pharmacological properties to those
      found in neurons. The only exception found was the glutamate-like action of 1 x
      10(-7) M MK-801, which partially prevented the early postdenervation
      depolarization when present in the muscle bath during the first 3 h after nerve
      section.

PMID- 9642671
TI  - Changes of acetylcholinesterase activity in various parts of brain following
      nontreated and treated soman poisoning in rats.
AB  - Changes of acetylcholinesterase (AChE) activity in various parts of the brain
      (frontal cortex, medulla oblongata, pons Varoli, cerebellum, hypothalamus, and
      hippocampus), following im sublethal non-treated and treated soman poisoning were
      studied. As a treatment, two antidotal mixtures containing atropine and either
      obidoxime or oxime HI-6 were used. This antidotal treatment was administered im
      for 30 s following soman intoxication. The AChE activities in the various brain
      tissues were evaluated at 1 and 3 h following soman administration. As expected,
      the highly toxic organophosphorus compound, soman, markedly inhibited AChE
      activity in all the brain sections at both time intervals. Both oximes had little
      influence on soman-induced AChE inhibition, but only the HI-6 mixture was able to
      reactivate soman-inhibited AChE significantly in some of the brain parts (frontal
      cortex, pons Varoli, hypothalamus). In the brain, the effect of HI-6 against
      soman-induced AChE inhibition is higher in comparison with obidoxime, but not
      quite satisfactory. Despite its limited effectiveness in the brain, HI-6 seems to
      be the most effective oxime yet found against soman poisoning because of its high
      reactivating effect in the peripheral compartment and other beneficial effects.

PMID- 9642672
TI  - Dual response of calpain to rat brain postdecapitative ischemia.
AB  - Calpains, Ca(2+)-dependent neutral proteinases (microM and mM Ca(2+)-sensitive),
      and their endogenous inhibitor calpastatin were examined in rat brain. Specific
      activity of m-calpain exceeded almost 10 times that of mu-calpain, and the both
      isoforms of calpain together with calpastatin were mainly located in the soluble
      fraction of homogenate. Acute postdecapitative ischemia of 15 min duration
      resulted in a gradual, time-dependent decrease of total mu-calpain activity (to
      60% of control values) and in the moderate elevation of calpastatin activity (by
      28%). The decrease of total mu-calpain activity coincided with its remarkable
      increase (above 300% of control values) in particulate fraction. In the case of m
      calpain, the only observed effect of ischemia was its redistribution and, as a
      consequence, the elevation of activity in particulate fraction. The accumulation
      of breakdown products, resulting from calpain-catalyzed proteolysis of fodrin (as
      revealed by Western blotting) indicated activation of calpain under ischemia. The
      findings suggest that this rapid activation involves partial enzyme translocation
      toward membranes, and is followed (at least in acute phase) by mu-calpain
      downregulation and increased calpastatin activity.

PMID- 9642673
TI  - Distribution and isoform diversity of the organellar Ca2+ pumps in the brain.
AB  - The gene family of organellar-type Ca2+ transport ATPases consists of three
      members. SERCA1 is expressed exclusively in fast skeletal muscle; SERCA2 is
      ubiquitously expressed, whereas SERCA3 is considered to be mainly expressed in
      cells of the hematopoietic lineage and in some epithelial cells. In the brain,
      the organellar-type Ca2+ transport ATPases are almost exclusively transcribed
      from the SERCA2 gene. Four different SERCA2 mRNAs have been described (classes 1
      4). However, unlike in nonneuronal cells, which express the class 1, 2, and 3
      splice variants, the main SERCA2 mRNA in the brain is the class 4 messenger.
      Similar to classes 2 and 3, the class 4 codes for the ubiquitously expressed
      SERCA2b protein. Recently, we have reported the distribution of the SERCA
      isoforms in the brain (Baba-Aissa et al., 1996a,b). SERCA2b was present in most
      neurons of all investigated brain regions. The highest levels were found in the
      Purkinje neurons of the cerebellum and in the pyramidal cells of the hippocampus.
      Interestingly, SERCA3 and SERCA2a are coexpressed along with SERCA2b in the
      Purkinje neurons, but are weakly expressed in the other brain regions if present
      at all. Since these three protein isoforms have a different affinity for Ca2+,
      their possible roles in relation to Ca2+ stores in neurons are discussed.

PMID- 9642674
TI  - Decreased expression of natriuretic peptide A receptors and decreased cGMP
      production in the choroid plexus of spontaneously hypertensive rats.
AB  - Atrial natriuretic peptide receptor (ANP) subtypes and their signal transduction
      response were characterized in choroid plexus of spontaneously hypertensive (SHR)
      and normotensive (WKY) rats. We found two ANP receptor subtypes, guanylate
      cyclase coupled and uncoupled, in both rat strains. Binding of ANP was lower in
      SHR choroid plexus when compared to WKY. The lower ANP binding in SHR was the
      result of a decrease of binding to the guanylate cyclase-coupled receptor subtype
      A, a decrease that correlated well with the decreased ANP-induced cGMP formation
      in SHR. Forskolin stimulated cGMP production to the same extent in both strains.
      In WKY rats, ANP increased basal and forskolin-stimulated cAMP production;
      conversely, in SHR, ANP did not affect the basal level of cAMP and inhibited the
      forskolin-stimulated cAMP production. These results demonstrate differences in
      ANP receptor subtype expression, and ANP signal transduction in choroid plexus of
      hypertensive and normotensive rats, which is of possible significance to the
      central mechanisms of blood pressure control.

PMID- 9642675
TI  - Mechanisms of hippocampal reoxygenation injury.
AB  - Mechanisms of 12 min of hypoxia and subsequent reoxygenation were studied in rat
      hippocampal slices. General cell injury in reoxygenation was indicated by
      increased lactate dehydrogenase (LDH). Increase in conjugated dienes (CD) showed
      that oxygen radical burst induced lipid peroxidation (LPO). ATP increase was also
      involved in reoxygenation injury, since cyanide, an inhibitor of ATP synthesis,
      decreased this damage. The results obtained on using inhibitors of oxygen
      radicals generation, i.e., allopurinol, indomethacin, rotenone, and antimycin A,
      strongly suggest that the sources of oxygen radicals were the xanthine/xanthine
      oxidase system, prostaglandin synthesis, and mitochondrial respiratory chain. The
      involvement of oxygen radicals in oxidative stress was confirmed also by using
      chain-breaking antioxidants, trolox alpha-tocopherol and stobadine, [(-)-cis-2,8
      dimethyl-2,3,4,4a,5,9b-hexahydro-1H-pyrido (4,3b)indole]. Stobadine added at the
      onset of reoxygenation was most effective, acting in a dose-dependent manner and
      found to be without effect when applied in hypoxia. Cytochrome-c oxidase was
      decreased in reoxygenated hippocampal slices treated with stobadine.

PMID- 9642676
TI  - Neurochemical changes in the spinal cord in degenerative motor neuron diseases.
AB  - Human amyotrophic lateral sclerosis (ALS), a typical motor neuron disease, is
      characterized pathologically by selective degenerative loss of motoneurons in the
      CNS. We have demonstrated significant reductions of neurotransmitter-related
      factors, such as acetylcholine-(ACh)-synthesizing enzyme activity and glutamate
      and aspartate contents in the ALS, compared to the non-ALS spinal cord obtained
      at autopsy. We have also shown considerable reductions in activities of
      cytochrome-c oxidase (CO), an enzyme contributing to aerobic energy production,
      and transglutaminase (TG), a Ca(2+)-dependent marker enzyme for tissue
      degeneration, in the ALS spinal cord. We found marked increases in fragmented
      glial fibrillary acidic protein (GFAP), a filamentous protein specifically
      associated with reactive astrocytes, in the ALS spinal cord relative to non-ALS
      tissue. These biochemical results corresponded well to pathomor-phological
      neuronal degenerative loss and reactive proliferation of astroglial components in
      the ALS spinal cord tissue. However, these results only indicate the final
      pathological and biochemical outcomes of ALS, and it is difficult to follow up
      cause and process in the ALS spinal cord during progression of the disease.
      Therefore, we used an animal model closely resembling human ALS, motor neuron
      degeneration (Mnd) mutant mice, a subline of C57BL/6 that shows late-onset
      progressive degeneration of lower motor neurons with paralytic gait beginning
      around 6.5 mo of age, to follow the biochemical and pathological alterations
      during postnatal development. We detected significant decreases in CO activity
      during early development and in activity of superoxide dismutase (SOD), an
      antioxidant enzyme, in later stages in Mnd mutant spinal cord tissue. TG activity
      in the Mnd spinal cord showed gradual increases during early development reaching
      a maximum at 5 mo, and then tending to decrease thereafter. Amounts of fragmented
      GFAPs increased continuously during postnatal development in Mnd spinal cord.
      These biochemical changes were observed prior to the appearance of clinical motor
      dysfunctions in the Mnd mutant mice. Such biochemical analyses using appropriate
      animal models will be useful for inferring the origin and progression of human
      ALS.

PMID- 9642677
TI  - Tyrosine hydroxylase mRNA levels in locus ceruleus of rats during adaptation to
      long-term immobilization stress exposure.
AB  - The major central norepinephrinergic nucleus, locus ceruleus (LC), is thought to
      participate in modulation of such brain areas as cerebral cortex, septum,
      hippocampus, thalamus, hypothalamus, and cerebellum in animals facing various
      physiological challenges, including stress. Exposure of experimental animals to
      different stressors causes an increase in LC activity and gene expression of
      tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine
      biosynthesis. The aim of this work was to investigate the effect of a single and
      repeated (7 times) or long-term repeated (42 times) daily immobilization stress
      (IMMO) on TH mRNA levels in LC of laboratory rats by in situ hybridization
      method. A single IMMO caused significant elevation of LC TH mRNA levels in
      comparison to unstressed controls. This was found immediately and at 3 and 6 h
      after IMMO, and progressively increased up to 24 h after the first IMMO
      terminated. Further exposure to IMMO did not cause additional increases in LC TH
      mRNA levels, which stayed significantly elevated in comparison to unstressed
      rats. In animals that underwent IMMO for 42 times, the LC TH gene expression, 24
      h after the last stress exposure, was significantly lower when compared to that
      of singly or seven times stressed rats. Thus, our results indicate a possible
      adaptation of catecholamine-synthesizing system at the level of TH gene
      expression in LC of rats exposed to long-term repeated IMMO.

PMID- 9642678
TI  - Effect of phenol on the ion currents of frog nerve ending.
AB  - The effect of phenol on the transmitter release was studied at the neuromuscular
      junction of a frog cutaneous pectoris muscle using the extracellular
      microelectrode technique. It was shown that phenol (0.5 mM) enlarged the quantal
      content of the end-plate currents (EPCs), and it caused the increase of duration
      of the second negative and third positive phases of the triphasic response
      observed experimentally. The amplitude of the third phase (outward K+ current)
      decreased, and one of the second phase was unchanged. The effect of phenol
      remained in the presence of the Ca(2+)-channel blockers (Co2+, Mn2+), and
      disappeared in the presence of the tetraethylammonium (TEA) and 4-aminopyridine
      (4-AP). The results suggest that phenol changes the kinetics of the voltage
      dependent K+ current, which is one of the mechanisms of the phenol facilitating
      effect at the synaptic transmission.

PMID- 9642679
TI  - Eleanor Roosevelt Institute.

PMID- 9642680
TI  - Establishing a link between oncogenes and tumor angiogenesis.
AB  - We have tried to stress that mutant oncogenes or overexpressed, nonmutated proto
      oncogenes, in addition to their direct affect on promoting aberrant tumor cell
      proliferation (and survival), may possess a crucial indirect means of stimulating
      tumor cell growth through regulation of angiogenesis. This effect would never be
      observed in tissue culture studies of oncogene function using pure cultures of
      tumor cells, which probably helps explain why the pro-angiogenic function of
      oncogenes has not been appreciated until only relatively recently. Indeed, the
      very first indication of a possible contributory role of oncogenes, such as ras
      and myc, to tumor angiogenesis was first reported by Thompson et al. in 1989, who
      used reconstituted organ cultures of the mouse prostate gland for their studies
      (69). This potentially important contribution of oncogenes to tumor growth and
      development may prove to have an impact on how various signal transduction
      inhibitors that are now in early phase clinical trials, e.g., monoclonal
      neutralizing antibodies to the human EGF receptor (70), function in vivo as anti
      tumor agents.

PMID- 9642681
TI  - Convergence and divergence of the signaling pathways for insulin and
      phosphoinositolglycans.
AB  - Phosphoinositolglycan molecules isolated from insulin-sensitive mammalian tissues
      have been demonstrated in numerous in vitro studies to exert partial insulin
      mimetic activity on glucose and lipid metabolism in insulin-sensitive cells.
      However, their ill-defined structures, heterogeneous nature, and limited
      availability have prohibited the analysis of the underlying molecular mechanism.
      Phosphoinositolglycan-peptide (PIG-P) of defined and homogeneous structure
      prepared in large scale from the core glycan of a glycosyl-phosphatidylinositol
      anchored membrane protein from Saccharomyces cerevisiae has recently been shown
      to stimulate glucose transport as well as a number of glucose-metabolizing
      enzymes and pathways to up to 90% (at 2 to 10 microns) of the maximal insulin
      effect in isolated rat adipocytes, cardiomyocytes, and diaphragms (G. Muller et
      al., 1997, Endocrinology 138: 3459-3476). Consequently, we used this PIG-P for
      the present study in which we compare its intracellular signaling with that of
      insulin. The activation of glucose transport by both PIG-P and insulin in
      isolated rat adipocytes and diaphragms was found to require stimulation of
      phosphatidylinositol (PI) 3-kinase but to be independent of functional
      p70S6kinase and mitogen-activated protein kinase. The increase in glycerol-3
      phosphate acyltransferase activity in rat adipocytes in response to PIG-P and
      insulin was dependent on both PI 3-kinase and p70S6kinase. This suggest that the
      signaling pathways for PIG-P and insulin to glucose transport and metabolism
      converage at the level of PI 3-kinase. A component of the PIG-P signaling pathway
      located up-stream of PI 3-kinase was identified by desensitization of isolated
      rat adipocytes for PIG-P action by combined treatment with trypsin and NaCl under
      conditions that preserved cell viability and the insulin-mimetic activity of
      sodium vanadate but completely blunted the insulin response. Incubation of the
      cells with either trypsin or NaCl alone was ineffective. The desensitized
      adipocytes were reconstituted for stimulation of lipogenesis by PIG-P by addition
      of the concentrated trypsin/salt extract. The reconstituted adipocytes exhibited
      65-75% of the maximal PIG-P response and similar EC50 values for PIG-P (2 to 5
      microns) compared with control cells. A proteinaceous N-ethylmaleimide (NEM)
      sensitive component contained in the trypsin/salt extract was demonstrated to
      bind in a functional manner to the adipocyte plasma membrane of desensitized
      adipocytes via bipolar interactions. An excess of trypsin/salt extract inhibited
      PIG-P action in untreated adipocytes in a competitive fashion compatible with a
      receptor function for PIG-P of this protein. The presence of the putative PIG-P
      receptor protein in detergent-insoluble complexes prepared from isolated rat
      adipocytes suggests that caveolae/detergent-insoluble complexes of the plasma
      membrane may play a role in insulin-mimetic signaling by PIG-P. Furthermore,
      treatment of isolated rat diaphragms and adipocytes with PIG-P as well as with
      other agents exerting partially insulin-mimetic activity, such as PI-specific
      phospholipase C (PLC) and the sulfonylurea glimepiride, triggered tyrosine
      phosphorylation of the caveolar marker protein caveolin, which was apparently
      correlated with stimulation of lipogenesis. Strikingly, in adipocytes subjected
      to combined trypsin/salt treatment, PIG-P, PI-specific PLC, and glimepiride
      failed completely to provoke insulin-mimetic effects. A working model is
      presented for a signaling pathway in insulin-sensitive cells used by PIG(-P)
      molecules which involves GPI structures, the trypsin/salt- and NEM-sensitive
      receptor protein for PIG-P, and additional proteins located in caveolae/detergent
      insoluble complexes.

PMID- 9642682
TI  - Advanced glycation endproducts in neurofilament conglomeration of motoneurons in
      familial and sporadic amyotrophic lateral sclerosis.
AB  - BACKGROUND: Massive neurofilament conglomeration in motor neurons has been
      described to occur in the early stages of both familial and sporadic amyotrophic
      lateral sclerosis (ALS). Previously, neurofilament conglomerates were
      immunolabeled for both superoxide dismutase (SOD1) and nitrotyrosine, suggesting
      the potential for oxidative nitration damage to neurofilament protein by
      peroxynitrite. Long-lived neurofilaments may also undergo modification by
      advanced glycation endproducts (AGEs) with concomitant generation of free
      radicals, including superoxide. This radical species may then react with nitric
      oxide to form the potent oxidant, peroxynitrite, which in turn can nitrate
      neurofilament protein. Such a glycated and nitrated neurofilament protein may
      become resistant to proteolytic systems, forming high-molecular-weight protein
      complexes and cytotoxic, neuronal inclusions. MATERIALS AND METHODS: Paraffin
      sections containing both neurofilament conglomerates and neuronal inclusions were
      obtained from patients with sporadic (n = 5) and familial (n = 2) ALS and were
      probed with specific antibodies directed against the AGEs cypentodine/piperidine
      enolone, arginine-lysine imidazole, pentosidine, and pyrraline. RESULTS:
      Neurofilament conglomerates, but not neuronal inclusions, were intensely
      immunolabeled with each of the anti-AGE antibodies tested. The immunoreactivity
      was selective for neurofilament conglomerates and suggested that AGEs may form
      inter- or intramolecular cross-links in neurofilament proteins. CONCLUSIONS:
      These data support the hypothesis that AGE formation affects neurofilament
      proteins in vivo and is associated with the concomitant induction of SODI and
      protein nitration in neurofilament conglomerates. AGE formation in neurofilament
      protein may not only cause covalent cross-linking but also generate superoxide
      and block nitric oxide-mediated responses, thereby perpetuating neuronal toxicity
      in patients with ALS.

PMID- 9642683
TI  - Multiparameter analysis of clastogenic factors, pro-oxidant cytokines, and
      inflammatory markers in HIV-1-infected patients with asymptomatic disease,
      opportunistic infections, and malignancies.
AB  - HIV-1-infected patients are in chronic oxidative stress and clastogenic factors
      (CFs) are present in their plasma. CFs from patients with HIV are formed via
      superoxide anion radical and stimulate further superoxide production. The
      pathophysiolgic significance and the exact composition of the circulating
      clastogenic material in patients with HIV is unknown. Cytokines, such as tumor
      necrosis factor-alpha (TNF-alpha), are increased in the plasma of patients with
      HIV and TNF-alpha shows clastogenic activity in vitro. The aim of this clinical
      study was to compare levels of CF in HIV-1-positive patients with asymptomatic
      disease, opportunistic infections, and malignancies with those in HIV-1-negative
      control groups and to correlate CF activity with CD4+ T cell numbers, the
      cytokines (TNF-alpha, interleukin-2 [IL-2], IL-6), and the inflammatory markers
      (C-reactive protein [CRP], neopterin, granulocyte elastase). CFs were
      significantly increased in all HIV-1-positive patients and in HIV-1-negative
      patients with malignant tumors. HIV-1-positive patients with Kaposi's sarcoma
      showed the highest CF activity in their plasma (p < 0.08). CFs appear very early
      in HIV infection, and they correlate negatively with CD4+ T cells, which are an
      indicator of disease activity. The presence of CF in the plasma of HIV-infected
      patients is not a general response to a viral infection because these factors are
      not increased in HIV-1-negative patients with viral infection (zoster). CFs are
      not specific for the HIV-1 infection; they also occur in HIV-1-negative patients
      with malignant tumors. There was a tendency towards a positive correlation (p <
      0.14) between CF and TNF-alpha but there was no positive correlation of CF with
      IL-2, IL-6, CRP, elastase, and neopterin levels. This indicates that TNF-alpha
      may be among the components of CF in HIV-1-infected patients. In addition, other
      unidentified components may contribute to the clastogenic activity of the plasma
      or the composition of CF may vary from patient to patient. Further clinical
      studies with larger sample populations are necessary to analyze the composition
      of CF in HIV-1-positive patients.

PMID- 9642684
TI  - Requirements for allergen-induced airway hyperreactivity in T and B cell
      deficient mice.
AB  - BACKGROUND: The pathogenesis of asthma is believed to reflect antigen-induced
      airway inflammation leading to the recruitment of eosinophils and activation of
      mast cells through cell-associated IgE. Controversies persist however, regarding
      the relative importance of different pathogenic cells and effector molecules.
      MATERIALS AND METHODS: A variety of gene-targeted mice were examined for the
      induction of cholinergic airway hyperresponsiveness (AH), allergic airway
      inflammation, mucus production, and serum IgE reactivity following intratracheal
      challenge with a potent allergen. AH was determined using whole-body
      plethysmography following acetylcholine challenge. Where possible, results were
      confirmed using neutralizing antibodies and cell-specific reconstitution of
      immune deficient mice. RESULTS: T and B cell-deficient, recombinase-activating
      gene-deficient mice (RAG -/-) failed to develop significant allergic inflammation
      and AH following allergen challenge. Reconstitution of RAG -/- mice with CD4+ T
      cells alone was sufficient to restore allergen-induced AH, allergic inflammation,
      and goblet cell hyperplasia, but not IgE reactivity. Sensitized B cell-deficient
      mice also developed airway hyperreactivity and lung inflammation comparable to
      that of wild-type animals, confirming that antibodies were dispensable. Treatment
      with neutralizing anti-IL-4 antibody or sensitization of IL-4-deficient mice
      resulted in loss of airway hyperreactivity, whereas treatment with anti-IL-5
      antibody or sensitization of IL-5-deficient mice had no effect. CONCLUSIONS: In
      mice, CD4+ T cells are alone sufficient to mediate many of the pathognomonic
      changes that occur in human asthma by a mechanism dependent upon IL-4, but
      independent of IL-5, IgE, or both. Clarification of the role played by CD4+ T
      cells is likely to stimulate important therapeutic advances in treatment of
      asthma.

PMID- 9642685
TI  - Effect of targeted mutation in collagen V alpha 2 gene on development of
      cutaneous hyperplasia in tight skin mice.
AB  - Collagen V plays a major regulatory role in the formation of heterotypic fibers
      of the dermis and cartilaginous tissues as well as in the assembly of
      extracellular matrix. The pN/pN mouse, which is defective in collagen V alpha 2
      gene, exhibits skeletal abnormalities, skin fragility, and alterations in the
      collagen fiber organization, whereas the TSK/+ mouse, which is defective in
      fibrillin-1, the major component of microfibrils present in the extracellular
      matrix, develops cutaneous hyperplasia and autoimmunity. We have studied the role
      of collagen V in the formation of heterotypic collagen fibers in F1 mice, which
      are obtained by breeding pN/pN with TSK/+ mice. Our results show that F1 progeny
      neither develop cutaneous hyperplasia nor produce anti-topoisomerase I
      autoantibodies, unlike TSK/+ mice. The diameter of the collagen fibrils in the
      skin is also comparable to that found in control mice. Thus, the phenotypic
      changes observed in the TSK mouse could be reversed by genetic complementation
      with a collagen V-defective mouse.

PMID- 9642686
TI  - [Clinical application of three-dimensional ultrasound imaging as intraoperative
      navigation for liver surgery].
AB  - Intraoperative hepatic ultrasonography provides a great deal of information about
      tumor location and vascular anatomy in the liver, and is an indispensable
      procedure for hepatic resection. However, an accurate three-dimensional
      understanding of ultrasound (US) images depends on the operator's skill and
      experience, as the original display is two dimensional. We developed a new three
      dimensional US (3D-US) image processing method by application of the intensity
      projection method to US. The minimum and maximum intensity projection can display
      the arrangement of blood vessels (hepatic veins and portal veins) and hyperechoic
      regions, respectively. The intensity projection from several points of view can
      reconstruct 3D imaging by cine-display. Moving a probe manually, images are taken
      and processed on a real-time basis (in about 10 seconds). 3D-US was used in 24
      patients undergoing hepatic resection, and allowed easy visualization of the
      tumors and vascular anatomy. It is considered to be an efficient and safe
      navigation system in liver surgery.

PMID- 9642687
TI  - [Surgical treatment for hepatocellular carcinoma: liver resection using
      transplantation techniques].
AB  - Ex situ partial liver resection was performed in 2 patients with hepatocellular
      carcinoma (HCC) with Child A-liver cirrhosis that was untreatable by conventional
      liver resection techniques. In both cases, an extended left lobectomy was first
      performed, and then the autologous lateral segment was transplanted after
      removing segment 4 (or + a part of segment 5, 8) together with the tumor by the
      bench procedure. Although there might have been no difference in preoperative
      liver function in these cases, the postoperative course was quite different. The
      first case was successful with an uneventful postoperative course, but, the
      second case went into postoperative liver failure and the patient died of
      multiple organ failure on the 20th postoperative day. The cause of liver failure
      in the second case might be attributable to: 1) prolongation of cold preservation
      time for the bench procedure (196 min); or 2) over reduction of the native
      remnant liver (right lobe) due to resection of the huge tumor. In conclusion, the
      technique using ex situ partial liver resection and transplantation of the
      remnant section of the liver might be a useful method to extend surgical
      treatment for some cases of HCC untreatable by conventional liver resection.
      However, the indications should be carefully considered in each case, since graft
      damage can occur rapidly during the bench procedure due to combined liver
      cirrhosis.

PMID- 9642688
TI  - [Treatment of hepatocellular carcinoma: application of vascular surgery].
AB  - The present status of hepatic resection for hepatocellular carcinoma (HCC) is
      reviewed with special reference to the vascular aspects. Hepatic resection
      combined with portal tumor thrombectomy has been attempted in Japan. This
      procedure may be effective in the prevention of rupture of esophageal varices and
      making transcatheter arterial embolization possible. According to the report of
      Yamaoka and his associates, the 1- and 3-year survival rates of 29 patients
      treated with this combined procedure were 53% and 12%, respectively. This
      surgical strategy may thus yield survival benefits. In patients with a tumor near
      the confluence of the major hepatic vein and inferior vena cava, resection of
      segments 4b, 7, and 8 combined with hepatic vein reconstruction has been
      performed, which allows functional preservation of the residual liver. The
      historical development of hepatic vascular exclusion (HVE) is also reviewed. HVE
      can be performed safely using a centrifugal active pump, even in patients with
      cirrhosis. Hepatic resection combined with removal of tumor thrombus in the right
      atrium has been carried out using extracorporeal circulation. There are reports
      that at least two patients undergoing this operation survived more than 2 years
      after surgery. The hepatic warm ischemic time should be less than 60 min.
      Vascular surgery techniques are being increasingly applied in Japan for the
      treatment of HCC. Such surgery can be performed safely even in patients with
      cirrhosis. Improvement of long-term survival in patients undergoing such
      procedures remains an unresolved problem, however.

PMID- 9642689
TI  - [Long-term results after hepatectomy for hepatocellular carcinoma according to
      cancer stage].
AB  - The survival rates after hepatectomy for hepatocellular carcinoma (HCC) according
      to cancer stage were reported. The 5-year survival rates of Stage 1, 2, 3 and 4
      were 69.6%, 54.2%, 35.9% and 30.2%, respectively. A significant difference was
      observed between any neighboring two stages. But more than 5 years till 20 years,
      the survival curves cross at some times. That means after 5 years the influence
      of the anatomic condition of the initial cancer has been weak. Probably another
      factor which controls multi-centric carcinogenesis of HCC may work. When the
      survival rate was calculated dividing the stage group into two sub-groups
      according to liver function, with good function or poor function, the survival of
      the poor liver function group of any stage group was worse than that of the good
      liver function group of the nearest worse stage group. The survival after
      hepatectomy of HCC depends not only upon anatomic condition of the cancer but
      also upon the liver function.

PMID- 9642690
TI  - [Topical cooling as an adjunct for hepatectomy with inflow occlusion].
AB  - Hypothermia of the liver was developed to alleviate the ischemic insult induced
      by prolonged hepatic inflow occlusion. The use of hypothermia in liver surgery
      dates back to an experiment in 1953, which showed that the safe normothermic
      ischemic time of 20 minutes could be prolonged to 60 minutes with generalized
      cooling. Generalized cooling was first used clinically as an adjunct to
      hepatectomy with inflow occlusion in 1961. This method has not been widely used
      due to its adverse effect on systemic hemodynamics. Subsequently, methods of
      inducing hypothermia evolved to encompass in situ isolated hypothermic perfusion
      under total vascular exclusion, and then to hemihepatic hypothermic perfusion
      without the need for total vascular exclusion but with topical surface cooling.
      These technically feasible modifications were newly devised by our group. Our
      series of 39 hepatectomized patients, who underwent right-sided hepatectomy under
      hemihepatic inflow occlusion combined with topical surface cooling (October 1990
      to April 1997), demonstrated that even in livers associated with chronic liver
      disease, if surface topical cooling was interposed, a consecutive hemihepatic
      inflow occlusion time of as long as 60 +/- 23 minutes was acceptable without
      cyclic recirculation. In addition, no further ischemic insult occurred compared
      with a normothermic patient series with a significantly shorter occlusion time.
      Our data lead to the conclusion that the topical surface cooling method can be a
      useful and feasible adjunct to complicated hepatectomy in which inflow occlusion
      time is anticipated to prolong.

PMID- 9642691
TI  - [Pre- and/or postoperative adjuvant therapy for hepatocellular carcinoma].
AB  - Pre- and/or postoperative adjuvant therapy for hepatocellular carcinoma (HCC) is
      discussed. There is a high recurrence rate of HCC of up to 50% or more within
      three years after hepatectomy. More than 80% of those recurrences are in the form
      of intrahepatic metastases. Therefore it is extremely important to administer
      successful adjuvant therapy to prevent intrahepatic recurrence. There are two
      types of intrahepatic recurrence: simple dissemination from the primary focus of
      HCC; and newly developed HCC in the remnant liver. TAE is one option for
      preoperative adjuvant therapy to prevent intrahepatic recurrence. Postoperative
      adjuvant chemotherapy via the hepatic artery has occasionally been administered,
      but it is not yet established as an effective adjuvant therapy. However, a report
      by Muto et al showed that retinoid administration can prevent intrahepatic
      recurrence of newly developed HCC after hepatectomy. On the other hand, adjuvant
      therapy must not be tooaggressive, because: 1) HCC develops mainly in cirrhotic
      liver (with poor liver function); and 2) locoregional therapy for intrahepatic
      recurrence results in good survival rats even after detection of an established
      recurrence.

PMID- 9642692
TI  - [Percutaneous transhepatic portal vein embolization for hepatocellular
      carcinoma].
AB  - We report on the significance of percutaneous transhepatic portal vein
      embolization (PTPE) for hepatocellular carcinoma based on the results in 111
      patients who underwent PTPE in our hospital. All patients tolerated the procedure
      without major complications, although transient elevations in serum transaminase
      levels were noted. Immediately after PTPE, the portal pressure increased. Portal
      venous flow at the main portal trunk decreased, but the flow in the nonembolized
      part of the liver increased. PTPE produced regenerative hypertrophy in the
      nonembolized part of the liver, which was mainly predicted by the volume of the
      embolized area and the morphological score of the hepatitis or cirrhosis. PTPE
      increased the safety of subsequent hepatectomy and expanded the indications for
      hepatectomy. PTPE is also useful as a type of multiplicative therapy for
      hepatocellular carcinoma.

PMID- 9642693
TI  - [Systematic resection for hepatocellular carcinoma].
AB  - We have performed systematic subsegmentectomy in patients with hepatocellular
      carcinoma complicated mainly by cirrhosis. Such small anatomical resections have
      become possible due to the introduction of intraoperative ultrasonography and of
      vascular occlusion techniques. As a result of our clinical experience involving
      163 cases, it has been clarified that subsegmentectomy is a safe procedure
      (operative mortality rate, 0.6%) and results in a favorable long-term outcome (5
      year survival rate, 51%). In the resected specimens, microscopic cancer spread
      was recognized frequently (portal venous invasion, 41%; intrahepatic metastasis,
      31%). Subsegmentectomy is therefore the first procedure of choice in patients who
      have small hepatocellular carcinoma and chronic hepatitis or cirrhosis.

PMID- 9642694
TI  - [Hepatic resection using glissonean pedicle transection].
AB  - The basics of hepatic resection using the glissonean pedicle transection method
      are presented. The portal triad continues from the hepatoduodenal ligament to the
      intrahepatic portion in the from of the glissonean pedicle, i.e., the artery,
      portal vein, and bile duct are Combined with connective tissue and sheathed by
      the peritoneum in the form of a fibroid bundle. The full length of the primary
      branches and the origin of secondary branches are located extrahepatically, and
      the trunk of the secondary and more peripheral branches have an intrahepatic
      course. The ramification pattern of the tertiary branches of each secondary
      branch varies by individual. The liver is nourished by the 3 secondary branches
      of the glissonean pedicle. Each secondary branch supplies one segment, and
      therefore the liver can be divided into 3 segments and the additional caudate
      area. The area supplied by each of the tertiary branches is cone shaped ("cone
      unit"). Each segment is composed of from 6 to 8 cone units. The standard method
      for hepatic resection is the segmental resection method, in which one secondary
      branch is transected. In cases of limited resection, the number of cone units to
      be resected is adjusted, and the tertiary branches which supply them must also be
      transected selectively through the hilar or parenchymal approach. The author has
      performed hepatic resection using the glissonean pedicle transection method in
      834 consecutive patients with hepatocellular carcinoma with no trouble.

PMID- 9642695
TI  - [Xenotransplantation research for clinical practice].
AB  - In Japan a very strict brain death transplant bill has been effective since
      October 1997. However, the number of potential heart donors will be very few. In
      the United States and Europe, where most organ transplants are carried out, the
      chronic donor organ shortage has increased interest in the possible use of
      xenogeneic organs for transplantation in humans. Pigs, which are possible donors,
      now appear to be incompatible with humans and their organs will be hyperacutely
      rejected. The mechanism of hyperacute rejection is now well elucidated with
      clarification of the roles of complement and xenogeneic antigen. The strategies
      for overcoming hyperacute rejection involve creating transgenic pigs with
      insertion of human anti-complement genes and modification of their xenoantigens.
      The Japanese Society for Xenotransplantation has recently been established, ant
      the 5th International Congress for Xenotransplantation will be held in Nagoya in
      October 1999.

PMID- 9642696
TI  - [N-3 polyunsaturated fatty acids in surgical nutrition].
AB  - Recent surgical nutrition includes the management of mediator to induce the
      stress response and immune function. N-3 polyunsaturated fatty acid (n-3 PUFA)
      were reported to increase the survival rate, and to improve the nutritional and
      immune status of septic or burned animals. N-3 PUFA also inhibited the
      proliferation and metastasis of cancer, and improved the cancer cachexia. N-3
      PUFA decreased the production of cytokine and eicosanoid originated from n-6
      PUFA, and reduced the inflammatory and stress response. Cell-mediated immunity
      was suppressed with the reduction of cytokine. But in the stressed state, N-3
      PUFA ameliorated the stress induced immunosuppression. Alteration of
      transcription of cytokine mRNA, changes of membrane fluidity, and reduced
      expression of adhesion molecule were proposed to interpret these effects. In
      conclusion, n-3 PUFA can be applied for the surgical patients, especially for the
      critically ill patients.

PMID- 9642697
TI  - [A case of primary squamous cell lung cancer invading the wall of the distal
      aortic arch and the left subclavian artery: successful surgical management using
      ECC with selective cerebral perfusion].
AB  - A 37-year-old male was referred to our hospital with symptoms suggesting
      pneumonia. The preoperative diagnosis was primary lung cancer of the left upper
      lobe invading the distal aortic arch (DAA) (T4, stage IIIB). Complete resection
      was performed with associated resection of the pneumonectomy, DAA, and left
      subclavian artery. Dacron graft replacement was performed using ECC with
      selective cerebral perfusion. Histological examination revealed squamous cell
      carcinoma, n1 and negative surgical margins. We expect this patient to achieve
      long-term survival. We conclude that ECC with selective cerebral perfusion is
      both safe and effective for pulmonary surgery in cases with combined resection of
      the DAA.

PMID- 9642698
TI  - [A resected case of so-called carcinosarcoma of the lung which was diagnosed as
      diaphragmatic tumor].
AB  - A 64-year-old male complained of right hypochondralgia and was admitted to our
      hospital. A large tumor (10 x 15 x 10 cm) of the right diaphragm was detected
      involving the middle and lower lobe of the lung. Microscopic and
      immunohistochemical examinations showed that bronchiolo-alveolar cell carcinoma
      was interposed in the sarcoma-like lesion, and this tumor was diagnosed as a so
      called carcinosarcoma of the lung.

PMID- 9642699
TI  - Can we have it both ways?

PMID- 9642700
TI  - Capitated reimbursement for medical services returns control of the patient to
      the surgeon.
AB  - Limiting the spending on healthcare services is a societal necessity, whether
      externally budget-driven with reduced fee for service or salary, or internally
      controlled through prospective payment capitation. No reimbursement system is
      inherently good or bad. Ethical physicians will place patient well-being first
      and focus on the delivery of quality care, regardless of the payment method.
      There are several methods for the distribution of capitation payments to
      physicians, each with different levels of financial incentive to provide
      services. In one fully evolved embodiment of capitation, a payer carves out the
      entire orthopedic disease segment and contracts with an orthopedic organization
      for all musculoskeletal services within a defined geographic region. This form of
      capitation offers the advantage of returning control of patient care to the
      orthopedic surgeon.

PMID- 9642701
TI  - Capitation of specialty care is complex.

PMID- 9642702
TI  - Treatment of humeral fractures by closed reduction and retrograde intramedullary
      Ender nails.
AB  - A retrospective review of 94 humeral shaft fractures stabilized with retrograde
      Ender nails was performed to determine the safety and efficacy of this technique.
      Follow-up averaged 71 weeks. Eighty-six (91.5%) healed with no additional
      intervention (average: 14 weeks). There were eight (8.5%) nonunions. The
      functional results were good in 74 (81%), fair in 12 (13%), and poor in 5 (6%).
      There was one radial nerve palsy secondary to the operative procedure. The
      reoperation rate, including the repair of nonunions, was 19%. We conclude that
      intramedullary Ender nail fixation is a relatively simple and quick procedure,
      especially for the multiply injured patient, that adequately stabilizes most
      humeral fractures, yielding overall good results.

PMID- 9642703
TI  - Follow-up of intertrochanteric osteotomy of the hip during a 25-year period.
AB  - In 1984, in reporting follow-up on 67 hips in 61 patients who underwent
      intertrochanteric osteotomies for osteoarthritis of the hip, we found that
      between 12 and 15 years after osteotomy, 34% (23) of the 67 hips remained
      functional and the remainder had been converted to an arthroplasty. We now report
      on the fate of those osteotomies over a 25-year period. Ten patients with 10
      osteotomies did not require an arthroplasty, having died without requiring
      conversion to total hip arthroplasty at an average of 18.3 years after osteotomy
      (range: 11 to 24.1 years). Two others were living at an average of 25.2 years
      after osteotomy without requiring conversion. Thus, for 18% of the hips, no
      further hip surgery was performed. For the remaining 55 hips in 49 patients, the
      osteotomy had served for an average of 9.8 years (range: 1.3 to 26.1 years)
      before requiring arthroplasty. The cumulative probability of osteotomy survival
      was 57.8% (standard error: 6.0%) at 10 years, 20.0% (standard error: 4.9%) at 20
      years, and 5.7% (standard error: 2.9%) at 25 years by Kaplan-Meier survivorship
      analysis.

PMID- 9642704
TI  - ACL reconstruction in children with open physes.
AB  - Nine male patients with wide open physes who underwent intra-articular anterior
      cruciate ligament (ACL) reconstruction using semitendinosus and gracilis tendon
      grafts passed through the tibial physis and over the top of the femoral condyles
      were retrospectively reviewed at an average follow-up of 39 months (range: 24 to
      72 months). Five patients underwent reconstruction < 6 weeks following injury
      (range: 11 days to 41 days); the other four underwent reconstruction 2, 3, 5, and
      24 months following injury. Seven patients had excellent results and fully
      returned to their sport. Mean Lysholm score in these patients was 99 (range: 95
      to 100), and the mean maximum KT-1000 difference (available for six patients) was
      2.8 mm (range: 0 to 5.5 mm). Four of six intact grafts had a mean maximum KT-1000
      difference < or = 3.5 mm. Two grafts ruptured and were considered failures (one
      complete rupture at 10 months and one partial rupture at 3 years). Postoperative
      height increase averaged 10.7 cm (range: 4 to 22.9 cm). No patient had a
      clinically significant leg-length discrepancy, angular deformity, or radiographic
      evidence of physeal injury.

PMID- 9642705
TI  - Long-term results of the operative treatment of clubfoot: a representative study.
AB  - This study reports the long-term results of operative treatment of clubfoot. Of
      the patients who underwent posteromedial release for congenital clubfoot between
      1972 and 1975 at the Medical University in Pecs, Hungary, 41 feet of 30 patients
      have been under control examination. Control consisted of the distribution of
      questionnaires, physical examination, and in some cases, radiologic analysis. At
      an average of 20 years postsurgery, good clinical results were observed in 31
      (75%) feet. In these patients, satisfying foot form and good function were
      achieved, yet the characteristic atrophy of the calf and shortening of the foot
      were visible. Abnormal conditions were found in 10 feet, consisting of
      overcorrection in 6 and undercorrection in 4 cases. Subjective judgment of the
      patients was considerably better; only 5 (12%) feet had no satisfying results.
      Data of feet in an incorrect position were analyzed and compared with other
      cases. In cases of feet operated on in patients aged > or = 1 year and in
      patients who underwent multiple operations, abnormalities were found in a
      significantly higher percentage.

PMID- 9642706
TI  - A simple outpatient test for proprioception in the anterior cruciate ligament
      deficient knee.
AB  - Proprioception was quantified in 32 patients who had an arthroscopically
      documented complete anterior cruciate ligament tear using a simple single-limb
      standing test. An age-matched control group underwent identical testing. Control
      subjects demonstrated identical values between their two limbs, with the mean
      variation being 4.8%. The test group, however, showed significantly higher mean
      values for the injured compared with the noninjured limb, the mean variation
      being 43.8%. Patients who have a complete tear of the anterior cruciate ligament
      may experience a decline in proprioceptive function of their knees. This can be
      tested clinically using a simple single-limb standing test in an outpatient
      setting.

PMID- 9642707
TI  - C-reactive protein in orthopedics.

PMID- 9642708
TI  - Polymethylmethacrylate removal from the femur using a crescentic window
      technique.
AB  - This article describes a technique to aid in removal of polymethylmethacrylate
      during total hip arthroplasty revision. The technique is a modification of prior
      windowing techniques and requires no specialized instruments, offers substantial
      flexibility regarding cement removal and femoral prosthetic choice, and minimizes
      the amount and duration of stress on the femur. The technique involves making an
      oblong window in the anterior or anterolateral femur. Proximal and distal
      osteotomies are made with a crescentic oscillating saw and connected by straight
      beveled anterior and posterior longitudinal osteotomies using a straight
      oscillating saw. Once the intramedullary canal is prepared, either a nonecmented
      or cemented femoral prosthesis can be placed. The cortical window is replaced
      with a single cable used for fixation.

PMID- 9642709
TI  - Location of the sacral pedicle, foramina, and ala on the lateral aspect of the
      sacrum: a radiographic study.
AB  - Twenty-one adult dry-bone sacral specimens were used to quantitatively determine
      the location of the sacral pedicle, foramina, and ala on the lateral radiographic
      view of the sacrum. The anterior and posterior sacral foramina from S1 to S3, the
      midlines of the anterior sacrum and cephalad border of the S1 vertebral body, and
      the lateral limit of the lateral sacral mass were outlined with wires. A lateral
      radiograph was taken, and measurements were made directly from the radiograph.
      The average sacral pedicle height for both male and female specimens was
      approximately 20 mm for S1, 12 mm for S2, and 7 mm for S3. The sacral foramina
      height averaged approximately 13 mm for S1 and S2, and 10 mm for S3. The average
      ala and S1 body-ala angles were 88 degrees and 35 degrees. The distance from the
      ala tip to the anterior aspect of the sacrum averaged 12 mm, and the average
      anterior height of the S1 vertebral body above the ala was 11 mm. These
      measurements, in conjunction with inlet and outlet radiographs, may aid in the
      recognition of the vital structures of the sacrum on the lateral radiographic
      view and enhance the safety of dorsal sacral screw placement.

PMID- 9642710
TI  - Total hip arthroplasty in patients with low-lumbar-level myelomeningocele.

PMID- 9642711
TI  - Fracture of the fabella: a case of posterolateral knee pain.

PMID- 9642712
TI  - Diskitis caused by Actinobacillus actinomycetemcomitans.

PMID- 9642713
TI  - Bilateral osteochondritis dissecans of the knee and elbow.

PMID- 9642714
TI  - Radiologic case study. Reflex sympathetic dystrophy.

PMID- 9642715
TI  - [Women and health].

PMID- 9642716
TI  - [Women and health in numbers. Puerto Rico, 1994].
AB  - The purpose of this study was to explore the health situation of women in Puerto
      Rico through the analysis of the causes of deaths in medical certification
      contained in death certificates. The data source used was the computer tape
      containing the data on deaths occurred in Puerto Rico during 1994. This tape was
      produced by the Puerto Rico Department of Health. The analysis of the main causes
      of deaths in women showed a trend associated with chronic and degenerative
      diseases. This trend is compatible with the one found in women over 65 years old.
      In women under 65 years of age, this trend was also observed, although other
      causes were also relevant, like deaths by external causes and AIDS. For the age
      groups of under 15, 15 to 44, 45 to 64 and 65 and over, the principal causes of
      deaths were: conditions related to the perinatal period, AIDS, cancer and heart
      and heart related diseases respectively. The degree of vulnerability to death
      from certain causes of mortality which changes in importance from one age range
      to another in the female population of Puerto Rico is shown by the results of
      this research project.

PMID- 9642717
TI  - [Legal secrecy: abortion in Puerto Rico from 1937 to 1970].
AB  - The essay discusses abortion in Puerto Rico from 1937 to 1970, concentrating in
      its legal status as well as its social practice. The research documents the
      contradictions between the legality of the procedure and a social practice
      characterized by secrecy. The essay discusses the role of the Clergy Consultation
      Service on Abortion in promoting the legal practice of absortion in Puerto Rico.
      It also discusses the ambivalent role of medical doctors who, despite being
      legally authorized to perform abortions to protect the life and health of women,
      refused to perform the procedure arguing abortion was illegal. The essay
      concludes with a brief discussion on perceptions of illegality regarding
      abortion, emphasizing the contradictions between the practice of abortion and
      that of sterilization in Puerto Rico.

PMID- 9642718
TI  - Abortion in Puerto Rico: the limits of a colonial legality.
AB  - This paper situates the current abortion practice and policy in Puerto Rico
      within the historical, political, and economic context of the colonial domination
      of the United States (US) over Puerto Rico. In particular, we pay attention to
      the hurdles that women face to obtain abortion services in Puerto Rico as a
      result of its colonial legality. Of particular significance is the overall low
      abortion ratio, and differential abortion ratio and access issues faced by women
      when grouped by an age-ethnicity category: unmarried teenagers, adult Puerto
      Rican women and, adult immigrant women from the Dominican Republic. The present
      hurdles to abortion access--related to information, abortion providers, economic
      situation, and government policies--are discussed within the colonial legality of
      abortion based on the US Supreme Court decision Roe v. Wade. Puerto Rico's case
      is situated within its broader history of population policies developed by the
      State since the 1930's. Of particular relevance is the antagonism that State
      managers have had towards abortion in spite of its legality. In this sense,
      abortion in Puerto Rico continues to be an unfinished business, in spite of its
      legality.

PMID- 9642719
TI  - [Women and health professions in Puerto Rico: 1990].
AB  - The main aim of the present study was to analyse the sex distribucion for the
      health related professions in Puerto Rico. This was a descriptive investigation.
      The data was obtained from the Census of Population and Housing of Puerto Rico,
      1990 and the fifth register of health professionals, 1989-92 from the Health
      Department of Puerto Rico. It was observed that women in the 90's are still
      participating, in the health professions, in occupations traditionally of their
      gender. Nevertheless, it has been observed an increased in the women's
      participation in those occupations usually performed by men such as: veterinary
      and podiatry. Women tend to be employed more frequently by the government. Men,
      on the other hand, are concentrated on those occupations with the highest
      prestige and status, in the health professions. In addition, a high proportion of
      men are employed on their own. In terms of income, women earn less income than
      men for almost all the health occupations taken into account.

PMID- 9642720
TI  - [To the northernmost part of the airlift bridge: the Puerto Ricans in the United
      States].
AB  - This article examines the available data on the health status of Puerto Rican
      women in the United States. Statistics on reproductive health, cancer and AIDS
      indicate that the health status of these women is lower than that of both their
      U.S. and island counterparts. Usually, the health of immigrants lies somewhere
      between that of the population of the country of origin, and that of the 'host'
      country. Puerto Rican women, however, deviate from this pattern. The health lag
      which U.S. Puerto Rican women are experiencing suggests that the social
      dislocation which accompanies migration has not diminished over time. Puerto
      Rican women in the U.S., on the contrary, seem to have lost protective factors
      that shielded them from certain risks without acquiring the monetary,
      psycological, and information resources which would allow them to adopt
      preventive measures and make a more effective use of the existing health
      services.

PMID- 9642721
TI  - [Feminization of old age in Puerto Rico].
AB  - As a result of the inequality of gender in life expectancy, there is a higher
      proportion of women than men in old age. The problems and changes that take place
      in this stage of life are basically women' problems so it can be stated that
      aging is a women's issue. Women face prejudices nor only for being women but also
      for being old, sexist and ageist prejudices. This article discusses areas in
      which women are affected as they aged such as: discrimination and ageism, poverty
      and loneliness, physical and social losses and changes. It will also present the
      positive aspects of being old and female.

PMID- 9642722
TI  - [Medical negligence in Puerto Rico: 1990-1996].
AB  - The purpose of this communication is to present the statistical information of
      the medical and hospital professional liability situation in Puerto Rico from
      1990 to 1996. The Medical Institutional liability is a topic of great relevancy
      and importance to the people of Puerto Rico and the leaders responsible for
      establishing policies for the health care services. The Reports on Medical and
      Hospital Professional Liability from 1991 to the 1996 produced by the Examining
      Physicians Board were reviewed. The liability claims from 1991 to the 1996
      totaled 4054. During the seven years analyzed, 3506 cases were closed against
      physicians and institutions, a payment was issued in 1272 cases (36.3%), for a
      total compensation of $56,268,053. The risk of a legal claim is greater for the
      group of Plastic Surgeons and Emergency Medicine. The probability of a plaintiff
      receiving a compensation payment in a case of medical malpractice is
      approximately 36%, usually receiving a third of the total of the award as
      suggested by the medical literature. A thoughtful analysis of the current medical
      liability situation and defensive medicine should be done with the purpose of
      protecting the fiduciary function of the physicians with respect to the health of
      their patients, this is the function that guarantees a physician-patient
      relationship that is healthy, righteous and empathic.

PMID- 9642723
TI  - [Analysis of survival of patients with end-stage renal disease in Puerto Rico,
      1970-1994].
AB  - To assess the survival probabilities of patients with end stage renal disease in
      Puerto Rico, the data from the United States Renal Data System from 1970 through
      1994 was analyzed. The Kaplan Meier method was used to determine the survival
      rate for the following variables: diagnosis, gender, age groups, treatment
      modality and health regions. The analysis included 7,527 patients reported to the
      United States Renal Disease System of which 4,295 (57%) patients were reported
      dead. The median time of survival rate (50%) was 47.7 months. There was
      significantly lower survival rate (p = 0.0001) for diabetics compared with all
      the other diagnosis. Age was also a strong predictor of survival (p = 0.0001) and
      modality treatment (p = 0.0001). We concluded that diabetes, the elderly and the
      hemodialysis modality, had the lower survival rate in the puerto rican
      population.

PMID- 9642724
TI  - [Use of health education services for persons living with HIV/AIDS patients in
      Puerto Rico: 1994-1995].

PMID- 9642725
TI  - A short history of electrophysiology and its techniques. Section III.
      Electrophysiological instruments and techniques.

PMID- 9642726
TI  - [Health-related quality of life: important result of cancer treatments].
AB  - Health related quality of life is an integral part of the outcomes of cancer
      treatment. The purpose of this manuscript is to describe the concept of quality
      of life of cancer patients, and to summarize the validation studies of the
      "Functional Assessment Cancer Therapy Scales" (FACT) in Hispanics. Results of the
      studies support the validity of the scale which has the following dimensions:
      physical well-being, social/family well-being, relationship with doctor,
      emotional well-being, and functional well-being. The validation work makes
      possible the assessment of quality of life in Hispanics. Clinical trials which
      assess health related quality of life as a treatment outcome provide baseline
      information for decision making in the financing of oncology treatments.

PMID- 9642727
TI  - [Medical humanities. Health communication contribution to clinical bioethics].

PMID- 9642728
TI  - [Lyme disease in Tunisia, results of a clinical and serological study (1992
      1996)].
AB  - Lyme disease was suspected in 271 patients seeking hospital care between 1992 and
      1996. The sera of all these patients were tested by ELISA for antibodies against
      Borrelia burgdorferi. Twenty-nine cases of Lyme disease were identified, each
      involving neurological and articular problems. These results demonstrate that
      Lyme disease occurs in Tunisia and suggest that this diagnosis should be
      considered more frequently in patients presenting with the characteristic
      symptoms.

PMID- 9642729
TI  - [Food habits outside the home by school children in Cotonou (Benin)].
AB  - Urban growth leads to the consumption of food outside the home, with the demand
      for street food coming particularly from school children. A survey of 240 primary
      school children aged 8 to 13 was carried out, by means of personal interviews.
      More than 90% were regularly given pocket money by their parents, and this money
      was used mainly for buying food from vendors inside or near their schools. Less
      than 20% of children ate breakfast at home before going to school. Food purchases
      occurred mostly before the end of school morning break and an average of 38 CFA
      Francs were spent on each purchase (7.6 US cents). A wide variety of foods were
      bought, mostly including cereals. This buying of food seems to be part of a
      family food strategy to reduce the preparation of breakfast at home. The
      combination of this demand, and the supply of food in schools provides a useful
      means for campaigns aimed at improving the quality of children's diets in the
      short and long term.

PMID- 9642730
TI  - [Cardiovascular risk factors: smoking in the context of recent events in
      Lebanon].
AB  - Epidemiological studies have demonstrated that cigarette smoking increases the
      incidence of myocardial infarction and sudden death. Psychological and physical
      stress, like smoking, activates the sympathetic adrenal medullary and pituitary
      adrenal cortical systems. We therefore thought that the effects of stress and
      smoking together might increase the risk of cardiovascular disease. The seventeen
      year Lebanese war was a source of real psychological stress. It was a very
      traumatic time for many citizens, forced to cope with the situation and its
      tragic consequences. We evaluated the effects of smoking and traumatic
      experiences during war using a study population of 46 Lebanese men aged between
      28 and 45. We determined hemodynamic characteristics, such as heart rate and
      arterial blood pressure, and plasma indicators (cortisol and thromboxane
      concentrations). We found that smoking itself significantly increased all of
      these variables. The increase was larger, but not significantly so, in smokers
      who had experienced traumatic events during the war. This study suggests that
      preventive efforts should be directed at those groups with combinations of risk
      factors (e.g. smoking and stress) rather than at groups with one risk factor
      only. Accurate assessment of risk factors, their predictive value and their
      interactions are vital for any program of preventive measures.

PMID- 9642731
TI  - [Viral hepatitis A: when a changing epidemiology implies a different
      prophylaxis].
AB  - Major progress has been made in the epidemiology and prophylaxis of hepatitis A
      virus (HAV) since it was first discovered in stool samples by MacCallum in 1973.
      Seven types of the virus have been described. Types 1, 2, 3 and 7 occur in humans
      and types 4, 5 and 6 in monkeys, but genotype is not correlated with antigenic
      response. Immunization with the HM175 viral strain or natural infection by any of
      the virus types gives protection against all types of HAV affecting humans.
      Serological tests detect all types of the virus and make it possible to carry out
      epidemiological studies anywhere in the world. HAV is common in very young
      children in developing countries. Most ten-year-old children are immune and have
      no clinical signs of the illness. HAV infection has become less common in
      developed countries due to improvements in hygiene. Less than 40% of people under
      the age of 30 have been immunized. Non-immune individuals have a high risk of
      developing clinical hepatitis if they become infected and the older the patient
      at the time of infection, the more severe the disease is likely to be. The
      introduction of HAV into groups in which the majority of individuals have not
      been immunized may result in major local outbreaks. Prophylaxis schemes are
      developed on the basis of epidemiology. Vaccination is not routinely recommended
      in developing countries, except for visitors to those countries. Vaccination is
      recommended for individuals in high-risk groups, such as health workers, cooks,
      sewer maintenance engineers and tourists, in developed countries. In countries
      with an intermediate level of risk (East Europe, the Middle East and Southeast
      Asia), there is a high level of HAV infection and a low level of immunization.
      Vaccination programs are likely to be of value in these countries.

PMID- 9642732
TI  - [Validation of an evaluation guide for healthcare training programs in the field
      of humanitarian efforts].
AB  - The training of healthcare professionals working in the field of humanitarian
      action is of fundamental importance but there have been few procedures for
      assessing the training programs. A specific guide was produced for the evaluation
      of healthcare training programs. It uses a three-pronged approach to improve the
      training of healthcare personnel, encouraging educators to take a fresh look at
      the way in which they work. The guide seeks to improve the efficiency of training
      by evaluating programs. The guide was tested on four training programs conducted
      by three non-governmental organizations in three countries: Handicap
      International in Cambodia and Mozambique, Medecins Sans Frontieres in Cambodia
      and Action Nord Sud in Brazil. Questionnaires, guides and appraisals were
      analyzed, and the results suggested that the guide was valid, reproducible and
      easy to use. However, it is vital to provide external educational assistance
      during evaluation, to promote the implementation of decisions, thereby improving
      training practices.

PMID- 9642733
TI  - [Activities of the African Institute of Tropical Ophthalmology, 1990-1997].
AB  - The African Institute of Tropical Ophthalmology (AITO) was founded in Bamako in
      1953. It is part of a regional structure, The Organization for Cooperation and
      Coordination in the Control of Major Endemic Diseases (OCCCMED). AITO is a WHO
      collaborating center for the prevention of blindness and has four aims: the
      provision of eye care, training (ophthalmologists, cataract surgeons, specialist
      nurses, spectacle manufacturers), research (epidemiology, clinical and surgical)
      and assessment of public eye care as a function of the needs of the member states
      of OCCCMED. The European Regional Program for the Prevention of Blindness and an
      International Sight First Program Center are located at AITO. AITO is at the
      heart of a network dedicated to fighting blindness, and its activities extend
      beyond the borders of the OCCCMED.

PMID- 9642734
TI  - [Health care activities at the African Institute of Tropical Ophthalmology].

PMID- 9642735
TI  - [Training at the African Institute of Tropical Ophthalmology in Bamako].
AB  - The African Institute of Tropical Ophthalmology (AITO) is an OCCCMED institute,
      founded in Bamako in 1953. The OCCCMED itself is based at Bobo Dioulasso (Burkina
      Faso). AITO is a WHO collaborating center for the prevention of blindness.
      Training is one of the main activities of the institute, along with eye care,
      research and assessment. The prevalence of blindness in sub-Saharan countries is
      about 1.2%, with blindness mostly caused by cataracts, trachoma, glaucoma and
      onchocercosis. The demand for eye care is high but there are currently too few
      trained personnel to satisfy that demand. Therefore, AITO's role in training eye
      care professionals is particularly important. The institute trains
      ophthalmologists, specialist nurses, eye surgeons (who remove cataracts) and
      spectacle manufacturers. Training is carried out within the framework of the
      community and apprenticeship in the workplace. The student must attain specific
      targets, listed in a "competency passport" issued at the start of training.
      Clinical and surgical ophthalmology and general eye care are taught. Training
      costs and grants are mostly paid by the Lions Club International Sight First
      Program or by the French Overseas Development Ministry. Since 1991, AITO has
      trained to graduation: 18 ophthalmologists; 24 eye surgeons; 83 specialist
      nurses; 16 spectacle manufacturers.

PMID- 9642736
TI  - [Future of ophthalmology nurses and physicians trained at the African Institute
      of Tropical Ophthalmology].
AB  - Six ophthalmologists and 24 specialist ophthalmology nurses from French-speaking
      African countries graduate from AITO each year. Their training focuses on the
      skills they will need to participate in the national programs to combat
      blindness. All the ophthalmologists (10) and specialist ophthalmology nurses (42)
      from Mali, Niger, Burkina Faso and Senegal, who graduated from AITO within the
      last ten years were interviewed. Eight of the ten ophthalmologists and all of the
      specialist nurses are currently working in national programs to combat blindness.
      The specialist nurses knew more about public eye health issues than about optics.
      The training given is appropriate for ophthalmology professionals working in
      these countries. The chief demand of both ophthalmologists and specialist nurses
      was that they should have continuous training and supervision.

PMID- 9642737
TI  - [Research at the African Institute of Tropical Ophthalmology].
AB  - Research is one of the four main activities of AITO. It is vital for the
      determination of health care priorities, and for the design, implementation, and
      evaluation of programs and projects in OCCCMED countries. Most of the research is
      surgical and focused on the diseases which cause blindness. Cataracts are the
      principal cause of blindness and have been the focus of many studies aimed at
      making surgery more accessible in terms of both geographical availability and
      cost. Trachoma is a major public health priority in the countries of the Sahel
      and a survey of its prevalence is underway in several countries. This study
      should lead to the development of preventive and curative treatments aimed at
      controlling blindness caused by trachoma by the year, 2020. Vitamin A deficiency,
      the cause of xerophthalmia and high mortality rates in infants, has been surveyed
      in several countries. A survey of glaucoma, another major cause of blindness
      which is often not recognized or treated, will be carried out in Bamako. Other
      studies focus on leprosy, malaria and the effects of visual disability on the
      quality of everyday life. It will be a major challenge over the next five years
      to develop the capacity within local populations to identify, design and
      implement research programs in community health aspects of ophthalmology that
      will take into account the needs and constraints of sub-Saharan Africa.

PMID- 9642738
TI  - [Synthesis of the blindness situation in the countries of the Organization for
      Cooperation and Coordination in the Control of Major Endemic Diseases].
AB  - The major causes of blindness in the OCCCMED states are cataracts, trachoma,
      glaucoma and oncocercosis. The prevalence of blindness is about 1.2% and there
      are about 880,000 blind individuals and 2,500,000 people with impaired vision.
      Cataracts were the cause of blindness in 440,000 people and the cause of visual
      impairment in 1,320,000 individuals. About 1,500,000 people were found to have
      oncocercosis, and about 24,000 were blind. The true rate of trachoma is unknown.
      Thirteen thousand cataracts are surgically removed in the region each year, the
      CSR (cataract surgery rate) being 210. In the last few years, national programs
      have been set up to combat blindness and equipment and training have been
      established. With a ratio of 1 ophthalmologist per 523,000 people, the WHO's
      objectives are becoming attainable.

PMID- 9642739
TI  - [Progress in the control of world blindness and future perspectives].
AB  - Worldwide, there are approximately 180 million severely visually impaired people,
      of whom some 45 million are blind. Cataract remains the major cause of blindness,
      especially in the less developed countries. Substantial improvements have been
      achieved in the control of blinding diseases, mainly in respect of onchocerciasis
      and xerophthalmia. More recently, a WHO alliance for the eradicating of trachoma
      by the year 2020 has been set up. In Africa, the situation remains critical in
      spite of significant improvements in the training of eye care personnel and the
      implementation of new eye care facilities. If no additional action is taken, the
      number of blind from cataract will steadily increase, mainly because of
      population growth and aging. Substantial further efforts should be made to make
      appropriate eye care accessible and affordable to all those in need.

PMID- 9642740
TI  - [Strategies to control cataracts].
AB  - Cataracts, often associated with aging (80%), are a major cause of blindness
      (more than 50% of cases of blindness in Africa), and for this reason, up to 80%
      of cases could be predicted or prevented. The socio-economic costs (care and loss
      of productivity) are increased by morbidity (blindness, impaired vision,
      congenital, complicated or infected cataracts). The biological determinants of
      cataracts account for the difficulties in developing and implementing effective
      preventive action. These epidemiological determinants (prevalence, incidence,
      increase in life expectancy) account for the size of the public health problem.
      The surgical removal of cataracts in Africa currently only deals with about 1% of
      the prevalence rate or 10% of the incidence. Cataracts are, however, easy to
      cure, resulting in great benefits to public health. The waiting list for cataract
      operations is very short because of social and cultural barriers which limit the
      acceptability and accessibility of treatment. Rather than formalizing the
      dogmatic choices of surgical techniques and structures (fixed, mobile,
      advanced?), we should promote all phases of treatment from active screening and
      the selection of cases for surgery to the follow-up of interventions and their
      impact. We should also increase public awareness, develop a system for the
      transfer of information that is effective and improve the cost-effectiveness and
      capacity of the region to provide high quality services on a large scale. We must
      promote patient satisfaction at all stages of treatment: its quality, its
      delivery and its low cost.

PMID- 9642741
TI  - [Cataracts, a way into the national health system of Mali?].
AB  - Cataracts are common in Mali, where there are 60,000 people awaiting surgery for
      blindness caused by cataracts. This major cause of disability in adults could be
      used as an effective entry point into the national health system. The development
      of an effective referral system should increase the recruitment from districts
      and increase the standing of the highest level health centers. Surgery should be
      decentralized and carried out at the district level. A specialist surgical team,
      based at the regional hospital, would operate with portable equipment in the
      district health centers, with patients being referred by peripheral health
      centers. The success of this approach depends on the development of strong
      functional relationships between peripheral and district health centers and of
      interpersonal relationships between the staff members involved. This new approach
      should lead to a major reduction in the level of disability whilst strengthening
      and promoting the district health system as a whole.

PMID- 9642742
TI  - [Strategies to control trachoma].
AB  - Epidemiological data for trachoma in Mali have suggested a number of ways in
      which blindness caused by trachoma could be prevented or cured: improvements in
      domestic and urban environments (e.g. sanitation), the provision of household
      water supplies, improvements in personal hygiene (through health education to
      promote the washing of children's faces), mass administration of local
      (tetracycline) or general (azithromycin) antibiotics and eyelid surgery using the
      method of Trabut. A cost-benefit analysis was performed for antibiotic
      distribution and eyelid surgery. Such a study is required to assess the value of
      environmental improvements and the provision of water supplies. Improvements in
      personal hygiene and environment are the only effective ways to reduce the
      incidence of trachoma, but eyelid surgery should be developed to prevent the
      blindness caused by trachoma.

PMID- 9642743
TI  - [Strategies to control glaucoma].

PMID- 9642744
TI  - [Strategies to control vitamin A deficiency].
AB  - Vitamin A deficiency is a major public health problem in the countries of the
      Sahel. It causes xerophthalmia and high rates of child mortality and it occurs
      mostly in underdeveloped regions. People of all ages may suffer from vitamin A
      deficiency but it is a particular problem in pre-school-age children. Each year,
      about 250,000 children throughout the world become blind due to vitamin A
      deficiency. Measles, pneumonia and diarrhea reduce the child's reserves of
      retinol and increase the dietary requirement for vitamin A. Improvement of social
      conditions is a radical approach to preventing vitamin A deficiency. Three
      strategies are currently in use: horticultural activities and health education;
      fortification of food products; distribution of high-dose vitamin A capsules.

PMID- 9642745
TI  - [Contamination of a drinking water distribution network originating in a
      toxoplasmosis epidemic].

PMID- 9642746
TI  - [Neurosarcoidosis].
AB  - Signs and symptoms of neurosarcoidosis are variable and depend on location and
      size of granulomas. Clinical studies suggest a rate of 5% and autopsy results a
      rate of more than 25% of central nervous system (CNS) involvement in sarcoidosis.
      Statistical analysis of 57,789 patients admitted to the Department of Medicine in
      Lucerne over an 11-year period revealed 51 patients (0.9/1000) with the diagnosis
      of sarcoidosis. Six of these (12%) had sarcoidosis affecting the CNS.
      Neurosarcoidosis presented as: leptomeningeal granulomas, cranial nerve palsy,
      hypothalamic-pituitary syndrome, diabetes insipidus, pareses, paresthesia,
      pyramidal signs, dementia, urine retention, and asymptomatic granulomas.
      Neurosarcoidosis has predilections for the base of the brain, cranial nerves
      (facial nerve palsy is the most common) and meninges, but any part of the CNS may
      be affected. Therefore, the diagnosis of neurosarcoidosis may be extremely
      difficult, especially when it occurs as an isolated finding. Positive findings in
      transbronchial biopsy and lavage may demonstrate asymptomatic pulmonary
      involvement in as many as 50% of patients with neurosarcoidosis. Angiotensin
      converting enzyme levels may be raised in the blood or cerebrospinal fluid in
      some 50% of cases. Kveim test has a low sensitivity in neurosarcoidosis and thus
      is of little use. Gallium uptake may demonstrate extracranial granuloma available
      for biopsy. All these tests, and also computed tomography and magnetic resonance
      imaging, may be helpful. However, when in selected cases with isolated CNS
      disease standard investigations are not conclusive, meningeal or cerebral biopsy
      may be required in order to exclude other causes such as other granulomatous
      disorders, tumor metastasis, lymphoma, vasculitis, Sjogren syndrome, infection,
      neurologic disease such as multiple sclerosis, or systemic diseases such as
      Whipple's disease. CNS involvement in the acute phase of the disease has a
      favorable prognosis, while chronic courses respond less well to therapy.
      Treatment is initiated most frequently with corticosteroids (0.5-1 mg/kg body
      weight/day or pulses of 1 g/day of methylprednisolone in severe cases).
      Improvement is seen within 1-2 months. Side effects of corticosteroids,
      aggressive disease or frequent recurrences may require other immunosuppressive
      drugs (methotrexate, azathioprine, chlorambucil, cyclosporine A). Cerebral
      irradiation may be successful in some cases when other treatments fail.

PMID- 9642747
TI  - [The Advanced Breast Biopsy Instrumentation (ABBI), a system for stereotactic
      excision of mammographically suspect nonpalpable findings in the breast].
AB  - Advanced Breast Biopsy Instrumentation (ABBI) allows radiologically guided
      stereotactic excision of non-palpable radiodense lesions with high accuracy.
      Tissue cylinders of 5, 10, 15 or 20 mm diameter and of variable lengths can be
      removed very accurately under local anaesthesia and on an outpatient basis.
      Thirty-six patients with suspicious clusters of microcalcifications (n = 29) and
      with round lesions (n = 7) of the breast were qualified for ABBI. We were able to
      perform the excisional biopsy in a total of 34 patients. The breast of one woman
      was too small to safely fit into the system and in another woman the lesion could
      not be visualized by the system. In 2/34 cases (6%), the excision was imprecise
      due to slight dislocation of the breast parenchyma by the advancing cylinder
      knife. In one case (3%), ABBI missed the target within a dense mastopathic
      breast. In all cases the excisions were well tolerated. No wound complications
      occurred and the cosmetic result was excellent. Histology revealed 28 benign
      (82%) and 6 malignant (18%) lesions. Among the 27 small microcalcifications there
      were 3 invasive carcinomas, 3 ductal carcinomas in situ (DCIS), 1 lobular
      hyperplasia, 14 mastopathies, 1 fibroadenoma, 1 duct papilloma and 4
      calcifications in scars. Four of the 7 round-shaped lesions were found to be
      fibroadenomas, 1 lobular hyperplasia, and 2 mastopathies. With the ABBI system,
      non-palpable breast lesions can be precisely localized and excised.

PMID- 9642748
TI  - [X-chromosomal bulbospinal muscular atrophy (Kennedy syndrome)].
AB  - Two brothers with slowly progressive weakness and congenital nystagmus are
      presented. DNA analysis confirmed X-linked recessive bulbospinal muscular atrophy
      (XBSMA, Kennedy's disease) by demonstration of increased size of a CAG-triplet
      repeat on the androgen receptor gene on the X-chromosome. XBSMA is characterized
      by almost symmetrical muscular atrophy, weakness and fasciculations predominantly
      of bulbar, facial and proximal muscles of the extremities, with onset in the
      third to fifth decade. Tendon reflexes are depressed and pyramidal signs are
      absent. Sensory symptoms are clinically rare, but sensory nerve action potentials
      are frequently abnormal. Additional symptoms are important for differential
      diagnosis, and include postural tremor, gynecomastia, diabetes mellitus,
      testicular atrophy and impotence. Differentiation of this hereditary disorder
      from treatable conditions such as multifocal motor neuropathy or amyotrophic
      lateral sclerosis is essential. Though life expectancy is normal, patients become
      disabled in the course of the disease and need supportive care. Periodic testing
      for diabetes is recommended, and genetic counseling should be provided for
      patients and their relatives.

PMID- 9642749
TI  - [From chondrocyte culture to joint cartilage replacement. Development of de novo
      cartilage in vitro].
AB  - Local repair of acute or chronic cartilage lesions has not been successful so
      far. An attempt has been made to use synthetic materials to improve the quality
      of the repair tissue, but no method has achieved reliable regrowth of normal
      hyaline cartilage with adequate biomechanical properties and bonding to
      surrounding tissue. After publication of the first short-term results of
      chondrocyte transplantation in patients with localized cartilage lesions of the
      knee joints by a Swedish group in 1994 [1], the situation seems to have changed.
      Even though the advantages of this method of chondrocyte transplantation is a
      matter of controversy, the interest in the so-called "Carticel" approach has
      grown steadily. Indeed, the technique was recently approved by the FDA, on
      condition of a randomized, "placebo"-controlled trial. In view of this rapid
      development, we feel that independent experimental studies are urgently needed.
      In this article we present our own results in synthesizing de novo cartilage from
      cultured and phenotypically stable chondrocytes in a truly three-dimensional
      cartilage-like polyanionic matrix. With the experience gained in animals, we
      expect to set the stage for future experimental therapy in young human patients
      with early cartilage lesions.

PMID- 9642750
TI  - [Painful discoloration of the forearm].

PMID- 9642751
TI  - [Adjuvant therapy of colorectal carcinoma--1998 status].
AB  - Colorectal cancer is the second leading cause of cancer death in western
      countries. The prognosis is strongly correlated to the TNM-staging system and
      patients with stage T3-4 and/or node positive disease are at high risk for
      locoregional or distant relapse. It is now widely accepted that patients with
      node positive colon cancer should be offered postoperative adjuvant chemotherapy.
      Evidence is accumulating that six months' adjuvant fluorouracil plus leucovorin
      is equivalent to twelve months' fluorouracil and levamisole, which reduces cancer
      related deaths by more than 30%. Other adjuvant treatment approaches are
      perioperative regional chemotherapy or monoclonal antibody treatment, and the
      results of trials comparing these different treatment options alone or in
      combination are eagerly awaited. In rectal cancer, the risk of locoregional
      recurrence can be more than 50% and this event is associated with a deterimental
      effect on quality of life. The technique of mesorectal excision and the use of
      radiotherapy, alone or in combination with chemotherapy, have evolved as the most
      important measures for prevention of locoregional recurrence. In addition,
      chemotherapy has proven to be effective in reducing metastatic relapse and
      prolonging survival. The timing of radiotherapy (pre- versus postoperative) and
      the optimal combination of chemotherapy with radiation are presently important
      research issues in resected rectal cancer. In both colon and rectal cancer, a
      common theme emerging from the experience of the last few decades is that
      administration of dose-intensive fluorouracil is key for the success of adjuvant
      treatment.

PMID- 9642752
TI  - Urinary iodine concentrations in swiss schoolchildren from the Zurich area and
      the Engadine valley.
AB  - To prevent iodine deficiency disorders in Switzerland, table salt is currently
      fortified at 15 mg iodide/kg salt. However, several recent reports have suggested
      that urinary iodine excretion is marginal or inadequate among segments of the
      Swiss population, including schoolchildren. There is concern that iodine intake
      in Switzerland may be approaching levels associated with signs of clinical
      deficiency. Previous studies measuring urinary iodine in Swiss children have
      encompassed only a limited geographic area in central Switzerland. We have now
      evaluated urinary iodine concentrations in 243 schoolchildren aged 5 to 13 years
      from the Zurich area and the Engadine valley. The mean urinary iodine for all
      children was 11.3 +/- 8.7 micrograms/dl. There was no significant difference
      between iodine levels in urine from children in the Engadine and those from
      around Zurich. There were also no significant gender differences in urinary
      iodine concentrations. The median urinary iodine concentration for all children
      was 9.6 micrograms/dl, below the threshold suggested by the World Health
      Organization (< 10 micrograms/dl) as indicative of mild iodine deficiency. 54.3%
      of the children had urinary iodine concentrations < 10 micrograms/dl and 11.5%
      had levels < 5 micrograms/dl. The results of this study suggest that the iodine
      status of some Swiss schoolchildren may no longer be adequate. They indicate the
      importance of intermittent monitoring of iodine status in Switzerland, where
      dietary habits and food supply patterns are changing. They also support the
      recent decision (February 1998) by the Swiss Federal Department of the Interior
      to increase the concentration of iodide in Swiss table salt, based on the
      recommendations of the Fluoride-Iodine Commission of the Swiss Academy of Medical
      Sciences.

PMID- 9642753
TI  - [What thrombolytic rate can be realized in acute myocardial infarct? Results of
      the Oltner Heart Emergency Study].
AB  - BACKGROUND: Despite the benefits of thrombolytic therapy, there is evidence that
      not all suitable patients are receiving it. Early and accurate recognition of the
      ECG changes of myocardial infarction is a prerequisite for effective thrombolytic
      treatment. METHODS: During the Olten Heart Emergency Study we prospectively
      evaluated 951 consecutive patients with symptoms suggestive of myocardial
      infarction who were cared for by the emergency networks connected with Olten
      Cantonal Hospital. MAIN OUTCOME MEASURES: The final diagnosis was myocardial
      infarction in 173 patients (18.2%). Diagnostic ST-segment elevation was found in
      48.6% and complete left bundle branch block in 13.9% of these patients,
      representing a total of 62.5% acute myocardial infarction patients eligible for
      thrombolysis based on the ECG findings. Using a time limit of 6 hours between
      onset of symptoms and hospital entry for small and medium-size myocardial
      infarctions and 12 hours for large infarctions, plus an age limit of 70 years for
      inferior and 75 years for anterior infarctions as exclusion criteria for
      thrombolysis, we found one or more contraindications for the use of thrombolytic
      therapy in 50.9% of these patients. The most prevalent contraindication was time
      delay in the prehospital phase in 38.2%, followed by advanced age in 34.5%.
      Medical contraindications to thrombolytic treatment were found to be present in
      only 10.9%. Extension of the prehospital time delay to 24 hours would have
      increased the candidates for thrombolytic treatment to 39.3%, and raising the
      upper age limit by 5 years would have increased them to 46.8%. CONCLUSIONS: Our
      figures for a theoretically adequate thrombolysis rate contrast with many
      previous studies and the clinical reality in different hospitals both in
      Switzerland and around the world. In view of the importance and socioeconomic
      consequences of thrombolytic treatment in myocardial infarction, studies focusing
      on possible reasons for discrepancies between guidelines for thrombolytic therapy
      and their implementation in hospital practice would appear to be a necessity in
      providing measures to improve patient care in this clinical setting.

PMID- 9642754
TI  - [National Research Program NFP 38: "Diseases of the nervous system"].
AB  - The aim of Programme 38 of the Swiss National Research Foundation is to enhance
      collaboration between basic science and clinical application, as related to
      diseases of the nervous system, over a 5-year period. The 15 ongoing projects are
      described. They are mainly concerned with mechanisms of pathogenesis and recovery
      of function, and ways of modifying them therapeutically after traumatic lesions
      or various diseases of the nervous system such as stroke, Parkinson's disease,
      Alzheimer's dementia, depression, meningitis, HMSN etc.

PMID- 9642755
TI  - [Acute abdomen in established multiple myeloma].

PMID- 9642756
TI  - [Electroencephalography in the human].

PMID- 9642757
TI  - [Prolonged video EEG monitoring in differential diagnosis of seizures and in
      presurgical epilepsy diagnosis].
AB  - Prolonged video-EEG-monitoring facilitates a correlation of clinical seizure
      semiology and corresponding EEG changes. Indications for prolonged video-EEG
      monitoring comprise differential diagnosis of epileptic and psychogenic seizures,
      correct classification of epileptic syndromes and presurgical evaluation of
      patients with medically refractory focal epilepsies. 6000 patients in Austria
      would benefit from epilepsy surgery with an additional 150 bis 200 new patients
      appearing each year. Presurgical evaluation consists of a non-invasive Phase I
      and an invasive Phase II. During Phase I each patient is evaluated with a
      prolonged video-EEG-monitoring with scalp-EEG, a MRI-scan, a SPECT- and/or PET
      scan, a neuropsychological evaluation and a Wada-test. If the epileptogenic zone
      cannot be localized adequately with these methods, invasive electrophysiological
      techniques with intracranial (epidural peg-electrodes, foramen-ovale electrodes,
      subdural strip or grid electrodes) or intracerebral electrodes (stereotaxically
      implanted depth electrodes) have to be applied. Epilepsy surgery renders 70 to
      80% of patients seizure free and thus can regarded an effective and safe
      treatment option for patients with medically refractory focal epilepsies.

PMID- 9642758
TI  - [Evoked potentials--indications and clinical value].
AB  - This paper deals with studies of evoked potentials in diseases of the peripheral
      and central nervous system. Indications and clinical value of visual evoked
      potentials, brain stem auditory evoked potentials, somatosensory evoked
      potentials and motor evoked potentials are evaluated for frequent neurological
      diseases.

PMID- 9642759
TI  - [Electrodiagnosis of focal neuropathies].
AB  - Electrodiagnostic techniques used in an EMG-Laboratory and the diagnostic value
      in focal mononeuropathies are presented. The electrodiagnostic techniques include
      nerve conduction studies and needle electrode examination. Measurement of distal
      latency, amplitude, conduction velocity and the finding of focal conduction block
      may localize the focal character of the mononeuropathy. The needle electrode
      examination gives further information about distribution, extent, activity, or
      chronicity of the disease, especially in cases with axonal injuries. Some normal
      electrodiagnostic patterns are presented, accompanied by some illustrative
      pathological cases.

PMID- 9642760
TI  - [Role of electrophysiology in diagnosis of polyneuropathies].
AB  - Most for polyneuropathies present in a uniform, distally accentuated, rather
      symmetrical pattern, although asymmetric or multifocal distributions occur. The
      main feature of diagnosis is the history of development and the neurological
      clinical examination. Neurophysiologic studies, mainly nerve conduction studies
      (motor and sensory), reflex studies and electromyography are very accurate, but
      unspecific tools in order to establish the diagnosis of polyneuropathies, define
      special electrophysiologic features and can also reveal undetected (subclinical)
      lesions. For clinical purposes most neuropathies can be divided according the
      nerve conduction studies in axonal, demyelinating and mixed types. In recent
      years additional electrophysiological features as conduction block have appeared
      and are still under discussion. The etiology of polyneuropathy has to be
      determined in each patient with scrutinity. Additionally to general diseases
      (e.g. diabetes), common toxins (e.g. alcohol), concurrent medication (e.g. some
      cytostatic drugs) also immunologic (e.g. vasculitis) and hereditary factors have
      to be considered. A nerve biopsy is only indicated after a thorough consideration
      of electrophysiology and ancilliary findings. This applies in particular to
      hereditary neuropathies, where genetic testing has become a highly reliable test
      replacing biopsy.

PMID- 9642762
TI  - [Statistics--lying, but properly].

PMID- 9642761
TI  - [Electromyography in myopathies].
AB  - Despite increasing importance of molecular genetics, electromyography has
      preserved its place as a valuable tool in the diagnostic procedure of myopathies.
      Conventional electromyography allows the assessment of spontaneous activity,
      motor unit action potentials and interference patterns. In myopathies,
      fibrillations and positive sharp waves can be found in the majority of the cases.
      Motor unit action potentials are of short duration, low amplitude and may show
      increased polyphasia and number of satellite potentials. The interference pattern
      may be of low amplitude and compact already at submaximal contraction. Compared
      to conventional electromyography, automatic interference pattern analysis
      provides quantitative results and has the higher sensitivity and specificity.
      Normal conventional or automatic electromyography does not exclude a myopathy.
      For diagnostic purposes, electromyography will be followed by muscle biopsy and
      DNA analysis in most of the cases.

PMID- 9642763
TI  - [Important results of about 45 years balneo-medical research in Bad Hall].
AB  - It was tried to show the most essential results of a approximately 45 years'
      research activity on the field of iodine balneology from the Paracelsus Institute
      and--since 1993--from the Paracelsus-Gesellschaft Bad Hall. The papers were
      concerned with: basical studies about the chemistry of the iodine waters,
      generation of special analytic methods and techniques for iodine determinations
      and for investigations of the iodine metabolism, generation of new therapeutical
      iodine applications (for example: eye iontophoresis, electro-aerosol; preparation
      of the iodine water for a mineral water indoor swimming-bath and for special
      therapy solutions), investigation of the (favourable) iodine effects on the
      cardiac and circulation system, on blood rheology, thyroid function, lipid
      metabolism and on the antioxidant defence mechanisms (with special consequences
      for arteriosclerosis, diabetes mellitus and cataract), also on visual function
      and eye diseases (retina, color perception, contrast sensitiveness, cataract, dry
      eye) and respiratory diseases. Comparative studies on patients and on
      experimental animals as well as model experiments (e.g. on connective tissue: in
      vitro studies; tissue cultures) have been used to objectify many empirically
      observed cure effects. Possible side-effects of a cure with iodine brine (e.g.
      iodism) were mentioned.

PMID- 9642764
TI  - Validation of antibody-based recognition by piezoelectric transducers through
      electroacoustic admittance analysis.
AB  - The development of immunosensors based on piezoelectric transducers is widely
      investigated due to their attractive potentialities. The quartz crystal
      microbalance (QCM) may give a direct response signal which characterizes the
      binding event between a sensitive layer, immobilized onto the surface transducer,
      and the analysis to be detected. However, for small biomolecules, such as some
      antigens, it is quite difficult to obtain an observable signal. This is mainly
      due to the lack of sensitivity of the commonly used QCM (5 to 10 MHz quartz
      crystal). Moreover, the mass estimated with the QCM response through the
      Sauerbrey equation and the mass which can be measured thanks to other analytical
      techniques, in our case an enzymatic assay, are different: the deposited mass is
      generally overestimated by the QCM. To validate QCM mass measurements and,
      therefore antigens recognition, the interactions of acoustic shear waves with a
      biolayer were investigated during enzyme adsorption onto the microbalance gold
      electrode or during the antibody/antigen binding. Electroacoustic admittance was
      measured around the resonance frequency of a 27 MHz quartz resonator in parallel
      with microbalance measurements. The parameters which characterize the quartz
      microbalance equivalent circuit were compared with the classical microbalance
      frequency. The mass overestimation, given by the microbalance, could be explained
      either by modification of the rheological properties of the sensitive layers
      and/or by an inadequacy of the assay performed.

PMID- 9642765
TI  - Visual detection of protein adsorption onto electrochemically oxidized aluminum
      surfaces.
AB  - Adsorption of proteins onto electrochemically oxidized aluminum surfaces by a
      simple visual observation was investigated. For this purpose, Ta and then A1 were
      sputtered onto glass slides (Al/Ta/glass slides). Al/Ta/glass slides were
      electrochemically oxidized in 0.4 M H3PO4 under the potentiostatic conditions.
      After the application of aqueous solutions of bovine, rabbit or human
      immunoglobulin onto the solid Al2O3 surfaces, a change in colour was monitored
      visually. It was found that all investigated proteins could successfully be
      adsorbed onto oxidized Al surfaces. This was manifested by a change in colour of
      the surface from tan to a purple or blue, depending on the concentration of
      proteins, coating time and degree of oxidation of the Al layer. Most importantly,
      when an aqueous solution of human IgG was applied on an anti-human IgG coated
      surface, a change in colour was also observed indicating that the adsorption
      process did not denature the molecular recognition sites. This type of antibody
      antigen reaction was confirmed on the example of anti-human prothrombin--human
      prothrombin. It is believed that this technology may be useful in developing
      immunosensors for a variety of applications.

PMID- 9642766
TI  - Sensing biological effectors through the response of bridged nucleic acids and
      polynucleotides fixed in liquid-crystalline dispersions.
AB  - The formation of three-dimensional structures of double-stranded nucleic acid and
      polynucleotide molecules, fixed in the structure of liquid-crystalline
      dispersions and bridged by polymeric chelate complexes is described. The bridging
      elements consist of alternating daunomycin molecules and copper ions. It is shown
      that these bridges between nucleic acid molecules stabilize cholesteric
      structures of the DNA liquid-crystalline dispersion. The formation of polymeric
      chelate bridges is accompanied by a remarkable increase of the intense circular
      dichroism (CD) band characteristic of the DNA-daunomycin cholesterics. These
      bridges are destabilized by a number of biologically relevant compounds and
      macromolecules, such as ascorbic acid, homocarnosine, bovine serum albumin and
      lysozyme. The dramatic change in the optical activity of the liquid-crystalline
      dispersions upon addition of these compounds makes them easily detectable. The
      sensitivity of the method, in the range of analytic concentration 10(-4)-10(-8)
      M, depends on the nature of the compound being tested. The response of bridged
      DNA structures to biological effectors observed here foresees their further
      development as biosensor devices for detecting the presence of biologically and
      pharmacologically relevant compounds.

PMID- 9642767
TI  - Genetic engineering of a single-chain antibody fragment for surface
      immobilization in an optical biosensor.
AB  - The development of a biosensor based on a genetically engineered biomolecule
      offers many potential advantages to sensors that rely on natural proteins only.
      Here we present how protein engineering techniques can be used to introduce a
      functional unit for surface immobilization into a single-chain antibody fragment
      (scFv). A peptide known to mimic the binding properties of biotin was fused to
      the carboxyterminus of the phosphorylcholine-binding scFv fragment of IgA
      McPC603. This fusion protein could be immobilized on a streptavidin monolayer.
      The resulting scFv monolayer was capable of binding a fluorescently labeled
      phosphorylcholine analog, as detected by total internal reflection fluorescence.
      In contrast, an scFv monolayer formed by introducing biotin through chemical
      modification was not capable of binding phosphorylcholine. These results
      demonstrate the utility of site-specific, oriented attachment strategies in the
      formation of protein monolayers in optical sensors, made possible by the use of
      protein engineering techniques.

PMID- 9642768
TI  - Analytical strategies for amperometric biosensors based on chemically modified
      electrodes.
AB  - Various strategies based on the use of chemically modified electrodes for the
      development of amperometric biosensors are described. Particular emphasis is
      placed on materials capable of catalyzing the oxidation of NADH and coupling
      these with enzymatic activities for biosensor construction. In terms of
      electrocatalysts, the discussion will centre on electrodeposited films of 3,4
      dihydroxy benzaldehyde (3,4-DHB) and related analogs as well as on
      electrodeposited films of transition metal complexes of 1,10-phenanthroline-5,6
      dione (phen-dione). Electrodeposited films of these materials have been coupled
      to the enzymatic activity of aldehyde dehydrogenase and alcohol dehydrogenase for
      the development of biosensors for aldehydes and ethanol, respectively.

PMID- 9642769
TI  - Simultaneous determination of maltose and glucose using a screen-printed
      electrode system.
AB  - A screen-printed sensor system consisting of a glucose oxidase (GOD) electrode
      and an amyloglucosidase/glucose oxidase (A/G) electrode was constructed to
      determine maltose and glucose simultaneously in a mixture. Sensor construction
      was optimised so that it contained 20 units of GOD/40 units of amyloglucosidase
      and 0.2 mM 1,1'-ferrocenedimethanol. These components were deposited onto a
      screen-printed carbon electrode and an outer membrane was printed from 3.5%
      hydroxyethyl cellulose (HEC) solution. The optimum pH was 4.8. The linear range
      of the system was up to 40 mM glucose or 20 mmol/L maltose with coefficients of
      variation (CVs) ranging from 3.5% to 5.29%. The results obtained by using the
      enzyme electrode system agreed well with those obtained by the Fehling titration
      method. When stored dry, especially at 4 degrees C, the enzyme electrodes showed
      good stability over four months.

PMID- 9642770
TI  - Surface modifications for the development of piezoimmunosensors.
AB  - Four different techniques for the immobilisation of proteins onto the gold
      electrode of a piezoelectric quartz crystal were investigated. The examined
      techniques were adsorption, avidin-biotin binding and two different types of
      covalent binding on self-assembled monolayers (SAM),
      dithiobis(succinimidylpropionate) (DSP) and a dextran modified thiol monolayer.
      The reaction of the immobilised proteins (bovine serum albumin (BSA) and anti
      human IgG) with their specific antibodies, anti-BSA and hIgG (50 and 200
      micrograms/ml) were studied using a quartz crystal microbalance and then
      compared. Many cycles of measurements were performed on the same crystal
      regenerating the gold surface with a solution of glycine.HCl, 100 mM, pH 2.1. The
      interactions of the immobilised reagents with non-specific antibodies were also
      studied. The adsorption protocol was the quickest, but did not allow regeneration
      with glycine.HCl. Thiol-dextran coated surfaces did not show any detectable
      response to non-specific reagents, but needed a very long and complicated
      protocol. DSP and avidin-biotin coating procedures were easy and not too long.
      They seemed to have the best characteristics of reproducibility among different
      crystals and possibility of regeneration of the coated surface, but the
      percentage of non-specific binding was high.

PMID- 9642771
TI  - An approach to conductometric immunosensor based on phthalocyanine thin film.
AB  - A new approach to conductometric biosensors utilizing iodine-sensitive
      phthalocyanine thin films has been proposed. The excellent sensitivity of the
      tetra-tert-butyl copper phthalocyanine (ttb-CuPc) to free iodine was used for the
      first time to detect a peroxidase-initiated reaction in an aqueous medium. To
      minimize the interfering effect of aqueous electrolytes on the impedance
      responses of the ttb-CuPc film itself, Au/Cr interdigitated planar electrodes
      bearing ttb-CuPc thin films were protected with hydrophobic gas-permeable
      membranes, namely thermally evaporated calixarene or plasma polymerized
      hexamethyldisiloxane films. Impedance spectroscopy data were analyzed in order to
      define the optimal operating frequency. An enzyme sensor with peroxidase
      immobilized in a cross-linked albumin matrix was tested. Its impedance responses
      were studied under variation of the substrate concentration, pH, ionic strength
      and buffer capacity. These results were used to define conditions for peroxidase
      linked immunoassay in subsequent tests. With the developed sensor, concentrations
      of IgG in 0.2-2 micrograms/ml range were measured in a competitive mode with
      satisfactory accuracy. The detection of IgG in both test solutions and blood
      serum samples has been demonstrated.

PMID- 9642772
TI  - Electropolymerization of pyrrole and immobilization of glucose oxidase in a flow
      system: influence of the operating conditions on analytical performance.
AB  - The in situ potentiostatic electropolymerization of pyrrole (Py) on a Pt
      electrode in a thin-layer amperometric cell and the entrapment of the enzyme
      glucose oxidase (GOx) for the determination of glucose are reported. Polypyrrole
      (PPy) is directly formed by continuous passage of a buffered solution of the
      monomer (0.4 M) and enzyme (250 U mL-1) at pH 7 at a flow rate of 0.05-0.1 mL min
      1 under a constant applied potential of +0.85 V vs Ag/AgCl decreases. The
      electrosynthesis of PPy by injection of 500 microL of a Py + GOx solution in a
      carrier electrolyte consisting of 0.05 M phosphate buffer and 0.1 M KCl at pH 7.0
      was also assayed. The influence of the electropolymerization conditions on the
      analytical response of the sensor to glucose was investigated. The analytical
      performance of the PPy/GOx sensor was also studied in terms of durability and
      storage life, as well as selectivity against electroactive species such as
      ascorbic acid and uric acid as a function of the thickness of the polymer film
      formed.

PMID- 9642773
TI  - Covalent coupling of immunoglobulin G to a poly(vinyl)alcohol-poly(acrylic acid)
      graft polymer as a method for fabricating the interfacial-recognition layer of a
      surface plasmon resonance immunosensor.
AB  - The synthesis of a terminally thiolated poly(vinyl)alcohol (PVA) grafted with
      Poly (acrylic acid) (PAA) side chains is described. The PVA-PAA graft polymer
      (PVAg) was end-tethered to silver surfaces via the terminal thiol functionality
      and the resultant mobile, hydrophilic polymer matrix exploited for the covalent
      immobilization of large quantities of polyclonal goat (anti-hIgG) antibody (IgG)
      with low levels of non-specific adsorption. An SPR immunosensor, fabricated with
      an IgG-PVA-silver interfacial layer proved capable of performing a sensitive
      label-free assay of human IgG antigen (hIgG) with minimal non-specific binding
      interference. A detection limit (DL) for hIgG from serum of 0.8 microgram/ml (5
      nM) and an assay sensitivity of 0.66 ng hIgG/mm2/nM are reported.

PMID- 9642774
TI  - Detection of multiple toxic agents using a planar array immunosensor.
AB  - A planar array immunosensor, equipped with a charge-coupled device (CCD) as a
      detector, was used to simultaneously detect 3 toxic analytes. Wells approximately
      2 mm in diameter were formed on glass slides using a photoactivated optical
      adhesive. Antibodies against staphylococcal enterotoxin B (SEB), ricin, and
      Yersinia pestis were covalently attached to the bottoms of the circular wells to
      form the sensing surface. Rectangular wells containing chicken immunoglobulin
      were used as alignment markers and to generate control signals. After removing
      the optical adhesive, the slides were mounted over a scientific grade CCD
      operating at ambient temperature in inverted (multipin phasing) mode. A two
      dimensional graded index of refraction lens array was used to focus the sensing
      surface onto the CCD. Solutions of toxins were then placed on the slide. After
      rinsing, Cy5-labeled antibodies were introduced. The identity and amount of toxin
      bound at each location on the slide were determined by quantitative image
      analysis. Concentrations as low as 25 ng/mL of ricin, 15 ng/mL of pestis F1
      antigen, and 5 ng/mL of SEB could be routinely measured.

PMID- 9642775
TI  - Monitoring specific interaction of low molecular weight biomolecules on oxidized
      porous silicon using ellipsometry.
AB  - Porous silicon dioxide surfaces have been used for monitoring the specific
      affinity binding of low molecular weight molecules to streptavidin. Streptavidin
      was immobilized to the porous silicon dioxide surface by spontaneous adsorption
      at pH 7.4. Binding of biotin and an oligopeptide synthesized by means of
      combinatorial chemistry were monitored with an in situ null ellipsometer.
      Measurements were also done with hydroxy-azobenzene-2-carboxylic acid and DL-6-8
      thioctic acid amide. The performance of porous silicon dioxide as a potential
      surface in biosensor applications was compared with a planar silicon dioxide
      surface. Porous silicon dioxide showed a 10-fold amplification of the response
      compared to planar silicon dioxide. It was possible to monitor the binding of
      biotin and the oligopeptide in the concentration range 2-40 microM. A response
      time as low as 30 s was obtained for the oligopeptide at 40 microM.

PMID- 9642776
TI  - DNA optical sensor: a rapid method for the detection of DNA hybridization.
AB  - A DNA optical sensor system is proposed based on the combination of sandwich
      solution hybridization, magnetic bead capture, flow injection and
      chemiluminescence for rapid detection of DNA hybridization. Bacterial alkaline
      phosphatase (phoA) gene and Hepatitis B virus (HBV) DNA were used as target DNA.
      A biotinylated DNA probe was used to capture the target gene onto the
      streptavidin-coated magnetic beads and a calf intestine alkaline phosphatase
      (CAP)-labelled DNA probe was used for subsequent enzymatic chemiluminescence
      detection. The detection cycle was less than 30 min, excluding the DNA
      hybridization time, which was about 100 min. Both the phoA gene and HBV DNA could
      be detected at picogramme or femtomole level. No response signal was obtained
      when target DNA did not exist in the sample. Successive sample detection could be
      made by removing the magnetic field and a washing step.

PMID- 9642777
TI  - Functional characterization of a conducting polymer-based immunoassay system.
AB  - Experiments have been performed to characterize the electrical properties and
      functionality of a poly(3-hexylthiophene)-coated platinum electrode developed as
      a sensor for immunoassay read-out. Admittance measurements were performed on the
      coated electrodes as a function of frequency. The admittance spectra obtained
      show that the sensor is capacitive in nature. A circuit model is presented for
      comparison to other conducting polymer systems. Dynamic sensor response is
      characterized by oxidizing the polymer via a hydrogen peroxide-iodide pathway.
      Hydrogen peroxide is introduced either by direct injection or through a glucose
      glucose oxidase reaction to determine electrode functionality and sensitivity.
      Sensor response to chemical oxidation is measured as a function of frequency and
      applied signal amplitude. System response is linear in frequency from 1 Hz to 70
      Hz and in excitation amplitude up to approximately 600 mV. System sensitivity is
      analyzed based on oxidant generation from the enzyme-initiated pathway, sensor
      baseline drift, and the noise band on the quiescent sensor current.

PMID- 9642778
TI  - Influence of anions on glucose electrode response: application to extending
      concentration range.
AB  - Nitrate anions are shown to be very effective inhibitors of glucose oxidase at
      acidic pH, much more so than halide anions. The inhibition is fully reversible.
      This effect could be used to extend the concentration range of glucose electrodes
      up to 0.556 M (100 g/l) at pH 4 in 0.5 M KNO3 and glucose could be assayed in
      undiluted fruit juices. The disadvantages of this method are: prolonged time of
      one measurement; and the loss of accuracy owing to very low response of the
      electrode.

PMID- 9642780
TI  - Current awareness in biosensors & bioelectronics.

PMID- 9642779
TI  - Bioelectronic noses: a status report. Part I.
AB  - The present state of the art to record or mimic electronically the human senses
      of olfaction and taste is characterized. In this part I, an introduction to our
      present understanding in the development of electronic and bioelectronic noses is
      given. Finally the natural olfactory system is described in detail.

PMID- 9642781
TI  - Personality dimensions in spotted hyenas (Crocuta crocuta).
AB  - Personality ratings of 34 spotted hyenas (Crocuta crocuta) were made by 4
      observers who knew the animals well. Analyses suggest that (a) hyena personality
      traits were rated with generally high reliability; (b) 5 broad dimensions
      (Assertiveness, Excitability, Human-Directed Agreeableness, Sociability, and
      Curiosity) captured about 75% of the total variance; (c) this dimensional
      structure could not be explained in terms of dominance status, sex, age, or
      appearance; and (d) as expected, female hyenas were more assertive than male
      hyenas. Comparisons with previous research provide evidence for the cross-species
      generality of Excitability, Sociability, and especially Assertiveness. Discussion
      focuses on methodological issues in research on animal personality and on the
      potential contributions this research can make for understanding the biological
      and environmental bases of personality.

PMID- 9642782
TI  - Use of experimenter-given cues during object-choice tasks by chimpanzees (Pan
      troglodytes), an orangutan (Pongo pygmaeus), and human infants (Homo sapiens).
AB  - In a series of experiments, chimpanzees (Pan troglodytes), an orangutan (Pongo
      pygmaeus), and human infants (Homo sapiens) were investigated as to whether they
      used experimenter-given cues when responding to object-choice tasks. Five
      conditions were used in different phases: the experimenter tapping on the correct
      object, gazing plus pointing, gazing closely, gazing alone, and glancing without
      head orientation. The 3 subject species were able to use all of the experimenter
      given cues, in contrast to previous reports of limited use of such cues by
      monkeys.

PMID- 9642783
TI  - Object permanence in orangutans (Pongo pygmaeus) and squirrel monkeys (Saimiri
      sciureus).
AB  - The authors tested orangutans (Pongo pygmaeus) and squirrel monkeys (Saimiri
      sciureus) on object permanence tasks. In Experiment 1, orangutans solved all
      visible displacements and most invisible displacements except those involving
      movements into 2 boxes successively. In Experiment 2, performance of orangutans
      on double invisible displacements and control displacements (assessing simple
      strategies) was compared. Orangutans did not use the simple strategy of selecting
      the box visited last by the experimenter. Instead, poorer performance on double
      invisible displacements may have been related to increased memory requirements.
      In Experiment 3, squirrel monkeys were tested using the procedure of Experiment
      1. Squirrel monkeys solved visible but did not comprehend invisible
      displacements. Results suggest that orangutans but not squirrel monkeys possess
      Stage 6 object permanence capabilities.

PMID- 9642784
TI  - Timing of presentation of prenatal auditory stimulation alters auditory and
      visual responsiveness in bobwhite quail chicks (Colinus virginianus).
AB  - One group of bobwhite quail embryos (Colinus virginianus) was exposed to 10
      min/hr of bobwhite chick contentment calls immediately followed by 10 min/hr of
      bobwhite chick distress calls. A 2nd group of embryos was exposed to the same
      auditory stimulation but in the opposite order of presentation. Postnatal testing
      revealed that chicks exposed prenatally to the bobwhite chick contentment call
      and distress call (in either order of presentation) continued to respond to
      maternal auditory cues into later stages of postnatal development compared with
      unmanipulated chicks. Chicks exposed prenatally to the contentment call followed
      by the distress call showed an accelerated pattern of visual responsiveness to
      maternal cues, whereas chicks exposed prenatally to the distress call followed by
      the contentment call showed deficits in the normal pattern of perceptual visual
      responsiveness, suggesting that the auditory stimulation precocial avian embryos
      encounter 1st is influential in directing early intersensory development.

PMID- 9642785
TI  - Modified sensory features of social stimulation alter the perceptual
      responsiveness of bobwhite quail chicks (Colinus virginianus).
AB  - This study examined the sensory features of postnatal social experience that
      bobwhite quail chicks (Colinus virginianus) require to maintain species-typical
      responding to maternal auditory-visual cues. Chicks were reared in 1 of 3
      conditions after hatching: altered tactile, auditory, or visual experience with
      siblings. Findings revealed that altered tactile, auditory, or visual experience
      during the first 36 or the first 72 hr following hatching modified chicks'
      preferential responding to species-specific maternal cues. During the second 36
      hr, altered tactile or auditory experience disrupted chicks' perceptual
      development, whereas altered visual experience did not affect species-typical
      responsiveness. Results indicate that (a) timing of early postnatal visual
      experience can affect early filial responsiveness to maternal cues and (b) normal
      sensory experience derived from early social interaction affects species-typical
      perceptual development.

PMID- 9642786
TI  - Status, age, and sex effects on performance of discrimination tasks in group
      tested rhesus monkeys (Macaca mulatta).
AB  - To assess the relation between performance and social or demographic variables,
      this study group tested a captive monkey colony on visual and manual
      discrimination problems. Animals could choose between differently colored, sand
      filled boxes, where hue signaled the initial probability of finding buried food
      items. Dominant animals and subadults were most successful in locating and
      retrieving incentives, but sex did not affect performance. Rank effects occurred
      without overt aggression, suggesting deference by subordinates as a mediating
      mechanism. Age effects may reflect changing attention patterns only evident in
      complex arenas where cue salience becomes diluted. Because these findings differ
      from studies of singly tested animals, they show that, in a social context, an
      individual's rank and age may define opportunities to gain or efficiently use
      information.

PMID- 9642787
TI  - Distinguishing intentional from accidental actions in orangutans (Pongo
      pygmaeus), chimpanzees (Pan troglodytes), and human children (Homo sapiens).
AB  - This study investigates the understanding of others' intentions in 2- and 3-year
      old children, chimpanzees (Pan troglodytes), and orangutans (Pongo pygmaeus).
      During training, subjects learned to use a discriminative cue to select a baited
      box. During testing, the experimenter placed a marker on top of the baited box to
      inform the subject of the reward's location. However, the experimenter also
      accidentally dropped the marker on top of an unbaited box, so that during any
      given trial the experimenter marked 2 boxes, 1 intentionally and 1 accidentally.
      All 3 species preferentially selected the box the experimenter had marked
      intentionally (especially during the initial trials), with 3-year-old children
      presenting the most robust results. These findings suggest that subjects
      understood something about the experimenter's intentions. The authors speculate
      that understanding of others' intentions may precede the understanding of others'
      beliefs both at the ontogenetic and phylogenetic levels.

PMID- 9642788
TI  - Why some capuchin monkeys (Cebus apella) use probing tools (and others do not).
AB  - Tufted capuchins (Cebus apella) were provided with a task that facilitated the
      use and modification of sticks as probing tools. It was found that subjects aged
      10 years or older at initial task exposure were less likely to use tools than
      were younger subjects. Furthermore, juveniles whose mothers died before the
      subjects were aged 3 years were less likely to use tools than were juveniles
      whose mothers survived through this period. The ability to use tools was not
      related to subject sex or to access to the tool site or raw tool materials.
      Subjects modified tools both before and during their use, and the relative
      percentage of tools modified increased with subject age. Thus, it appears that
      capuchins most readily acquire tool use before the age of 10 years and that early
      disruption of the mother-infant relationship has deleterious effects on the
      emergence of instrumental behavior.

PMID- 9642789
TI  - Serous gland dimorphism in the skin of Melanophryniscus stelzneri (Anura:
      Bufonidae).
AB  - Two serous gland types (I and II) in the skin of the Argentine toad
      Melanophryniscus stelzneri were discovered using light and electron microscopy.
      Glands of the two types differ in several traits: features of the products (both
      mature and immature), organelles involved in biosynthesis, and paths of serous
      maturation. No consistent differences, however, were detected between the
      myoepithelial sheaths encircling the secretory units. Type I glands manufacture
      vesicles containing a single dense body with a repeating substructure and conform
      to the fundamental secretory line of bufonid skin, a secretory line involved in
      biosynthesis of steroids. Type II glands synthesize granules of varying densities
      and seem to belong to a line of glands that secrete proteinaceous products. The
      occurrence of the two serous gland types in Melanophryniscus stelzneri is
      discussed in a comparison with current literature on the morphofunctional
      characteristics of anuran poison glands, which perform both regulative and
      defensive roles. It is suggested that di- or polymorphism in serous glands is an
      adaptive trait that allows differential release of active molecules on the body
      surface.

PMID- 9642790
TI  - Ovarian growth and folliculogenesis in breeding and nonbreeding females of a
      social rodent, the Zambian common mole-rat, Cryptomys sp.
AB  - Zambian common mole-rats are subterranean rodents that live in families with only
      one female breeding. Her offspring remain in the parental nest and do not
      reproduce. Behavioral experiments (Burda, '95) demonstrated that their apparent
      "sterility" is based on incest avoidance and individual recognition of family
      members. To elucidate whether some kind of morphologically apparent ovarian
      suppression still takes place in daughters, ovaries of females of known age,
      weight, and reproductive histories were examined histologically and
      morphometrically. The body mass of old females (more than 3 years of age) begins
      to decrease, and the ovaries seem to begin to atrophy at the age of about 3-6
      years. Ovaries in neonates exhibited primordial and primary follicles, sometimes
      clustered in nests. Ovaries of adult nonbreeding females expressed all stages of
      the follicular development up to tertiary follicles. Many unruptured luteinized
      follicles were present, but true corpora lutea as a morphological sign of
      ovulation were missing. Unruptured luteinized follicles also could be found
      (additionally to true corpora lutea) in ovaries of breeding females. The number
      of primordial follicles dropped rapidly during the first 2 years of age; the
      number of primary, secondary, and tertiary follicles was subject to individual
      variation; and there was no clear correlation with age or reproductive status.
      While a tendency to form accessory unruptured luteinized follicles may just
      reflect taxonomic affinities of bathyergids to hystricomorphs, the otherwise
      complete folliculogenesis in "sterile" daughters and the presence of unruptured
      luteinized follicles even in breeding females are further evidence that there is
      no hormonal suppression of the ovarial cycle. We suggest that ovulation in
      nonbreeding females is not actively suppressed by the breeding female, but
      instead that it is not released because the triggering mechanisms, most probably
      repeated copulation, are missing.

PMID- 9642791
TI  - Ultrastructure of the foregut and associated glands in the lung fluke,
      Paragonimus miyazakii (Digenea: Troglotrematidae), with particular reference to
      their functional roles.
AB  - The foregut and associated glands of a digenetic trematode, Paragonimus
      miyazakii, were examined in the forebody by transmission and scanning electron
      microscopy as well as by light microscopy, and their functional roles were
      discussed. The foregut is lined with a general tegument without spines and
      sensory receptors throughout its length, although it consists of the mouth,
      pharynx, and esophagus. This foregut tegument is regionally and intraregionally
      modified in appearance, suggesting the performance of auxiliary functions in
      digestion. This appearance is characterized by long, frequent cytoplasmic
      extensions of the apical tegument around the middle portion of the mouth and the
      anterior esophagus. Electron-dense granules and multimembranous and multilamellar
      bodies are developed in the tegument to various degrees, and elaborately in the
      apical layer of the prepharynx. A single type of unicellular gland is embedded in
      the antero-middle part of the worm in small groups. The gland cells synthesize
      clear secretory granules as a chief product, each granule with a pleomorphic,
      dense, core-like inclusion. Mature granules are elliptical in shape,
      approximately 500 nm in diameter, and are subsequently discharged into the
      prepharyngeal foregut lumen after passing through the elongated cytoplasm of the
      gland cell. In the prepharynx and pharynx, host blood cells are apparently
      processed for digestion. In the wide lumen of the esophagus, foodstuff could
      undergo sufficient digestion prior to absorption by the cecal epithelium.

PMID- 9642792
TI  - Experimental analysis of character coupling across a complex life cycle: pigment
      pattern metamorphosis in the tiger salamander, Ambystoma tigrinum tigrinum.
AB  - Developmental relationships among characters are expected to bias patterns of
      morphological variation at the population level. Studies of character development
      thus can provide insights into processes of adaptation and the evolutionary
      diversification of morphologies. Here I use experimental manipulations to test
      whether larval and adult pigment patterns are coupled across metamorphosis in the
      tiger salamander, Ambystoma tigrinum tigrinum (Ambystomatidae). Previous
      investigations showed that the early larval pigment pattern depends on
      interactions between pigment cells and the lateral line sensory system. In
      contrast, the results of this study demonstrate that the major features of the
      adult pigment pattern develop largely independently of both the early larval
      pattern and the lateral lines. These results suggest that ontogenetic changes
      that occur across metamorphosis decouple larval and adult pigment patterns and
      could thereby facilitate independent evolutionary modifications to the patterns
      during different stages of the life cycle.

PMID- 9642794
TI  - [Progress in the development of safer surgical procedures on the trachea and
      bronchi].

PMID- 9642793
TI  - Ontogeny of postcanine tooth form in the ferret, Mustela putorius (Carnivora:
      Mammalia), and the evolution of dental diversity within the Mustelidae.
AB  - This study describes dental development within the ferret, Mustela putorius,
      through study of the form of the carnassial teeth and the upper first molar at
      progressive growth stages. Primordial teeth were serially sectioned in sagittal
      and transverse planes and three-dimensional reconstructions of tooth primordia
      were generated using MacReco software. Regional growth of the crown and
      asynchronous maturation of the dental tissues were observed in each tooth. The
      upper carnassial blade develops early and the tooth increases in length rapidly.
      Lingual growth of the upper carnassial is less pronounced and the protocone and
      its surrounding region mature late. The lower carnassial blade develops early and
      the talonid is late to mature. Development of the upper first molar differs from
      carnassial development in the early emphasis upon transverse growth and reduced
      lengthwise expansion. The early development of the carnassial blades in the
      ferret is shared with other carnivores, and may reflect the functional
      significance of this feature. Later stages of tooth ontogeny differ among
      carnivoran taxa and the specialized morphology of ferret teeth results from an
      apparently truncated period of late tooth ontogeny. This suggests that carnivoran
      species may share a common path of early development that specifies the ontogeny
      of homologous tooth features and that in later stages developmental differences
      result in species-specific tooth forms.

PMID- 9642795
TI  - [Bronchoplasty for the complete cure and preservation of pulmonary function].

PMID- 9642796
TI  - [Tracheo-bronchoplasty--with special reference to the treatment outcome and
      postoperative complications at anastomosis sites].

PMID- 9642797
TI  - [Clinical significance of tracheo-bronchoplasty for patients with lung neoplasm-
      distance from the edge of the tumor to the resection line].

PMID- 9642798
TI  - [Progress on tracheo-bronchoplasty--study on minimal bronchoplasty and prevention
      of surgical wound dehiscence].

PMID- 9642799
TI  - [Progress on bronchoplasty--prognostic significance of bronchial artery
      preservation].

PMID- 9642800
TI  - [Laparoscopic surgery and treatment outcome in esophageal achalasia].

PMID- 9642801
TI  - [Laparoscopic surgical procedure using the Jekler and Lhotka method in esophageal
      achalasia].

PMID- 9642802
TI  - [Changes in surgical procedures for patients with reflux esophagitis due to
      recent introduction of laparoscopic surgery and proton pump inhibitors].

PMID- 9642803
TI  - [New laparoscopic surgical procedure using surgical mesh for patients with
      esophageal hernia].

PMID- 9642804
TI  - [Different therapeutic approaches for patients with bronchogenic cysts within the
      esophageal wall].

PMID- 9642805
TI  - [Evaluation of new therapeutic procedures in benign esophageal diseases].

PMID- 9642806
TI  - [Surgical therapy and follow-up on Stanford-A type dissecting aortic aneurysm].

PMID- 9642807
TI  - [Operative outcome on Debakey-I type aortic dissection].

PMID- 9642808
TI  - [Applicability of complete replacement of aorta viewed from early and remote
      operative results].

PMID- 9642809
TI  - [Strategy for improvement of operative results of broad aortic replacement for
      DeBakey-I type aortic dissection].

PMID- 9642810
TI  - [Surgical treatment of DeBakey-I type aortic dissection--with special reference
      to patients receiving complete aortic replacement].

PMID- 9642811
TI  - [Suitability of limited resection in lung cancer].

PMID- 9642812
TI  - Intentional limited resection for primary lung cancer.

PMID- 9642813
TI  - [Limited resection in primary lung cancer of peripheral origin].

PMID- 9642814
TI  - [Combination of broad segmentectomy and lymph node excision for early stage lung
      cancer as a standard operative method].

PMID- 9642815
TI  - [Recurrence of lung cancer in the residual lobe following anatomic
      segmentectomy].

PMID- 9642816
TI  - [Thoracoscopic limited resection for lung cancer].

PMID- 9642817
TI  - [Strategy for univentricular repair for complication of atrioventricular valve
      regurgitation, total anomalous pulmonary venous connection, and ventricular
      outflow obstruction].

PMID- 9642818
TI  - [Therapeutic strategy in Fontan procedure].

PMID- 9642819
TI  - [Surgical repair for single ventricle complicated with anomalous pulmonary venous
      drainage or atrioventricular valve insufficiency].

PMID- 9642820
TI  - [Strategy for univentricular repair for complication of atrioventricular
      insufficiency or pulmonary venous obstruction].

PMID- 9642821
TI  - [Strategy for Fontan procedure in asplenia syndrome associated with total
      anomalous pulmonary venous connection].

PMID- 9642822
TI  - [Surgical strategy for aortic valve stenosis associated with single ventricle who
      will be objects of Fontan procedure].

PMID- 9642823
TI  - [Strategy in annuloplasty for a juvenile patient with asymptomatic mitral valve
      prolapse].

PMID- 9642824
TI  - [Surgical treatment of mitral valve prolapse using the mitral apparatus to adjust
      proper length of artificial chordae].

PMID- 9642825
TI  - [Minimally invasive mitral valve plasty operations].

PMID- 9642826
TI  - [Aortic valve-sparing operation--determination of proper graft size and
      prevention of regurgitation ].

PMID- 9642827
TI  - [Aortic valve-sparing operation and selection of operative technique].

PMID- 9642828
TI  - [Annuloaortic repair for aortic regurgitation].

PMID- 9642829
TI  - [Thoracoscopic excision of right upper mediastinal lymph node for bulky N3 left
      lobe lung cancer].

PMID- 9642830
TI  - [Endoscopic mediastinal lymph node excision for bulky N2 lung cancer].

PMID- 9642831
TI  - [Combination of mediastinal lymph node excision and thoracoscopic pneumonectomy
      for a case of N2 lung cancer confirmed by mediastinoscopy].

PMID- 9642832
TI  - [Mediastinal and cervical lymph node excision for a case of stage-IV esophageal
      cancer].

PMID- 9642833
TI  - [Upper mediastinal lymph node excision for a case of stage-IV esophageal cancer].

PMID- 9642834
TI  - [Lymph node excision for a case of stage-IV esophageal cancer].

PMID- 9642835
TI  - [The Annals, which way does it go: the last two years (1996-1997)].

PMID- 9642836
TI  - [AIDS-related cryptococcosis: diagnostic aspects, prognostic and therapeutic
      implications].
AB  - Diagnostic techniques of AIDS-related cryptococcosis were assessed in a series of
      43 HIV-infected patients, and microbiological features were correlated to the
      clinical course and outcome of disease. Polysaccharide antigen detection was the
      most sensitive method for central nervous system infection, followed by direct
      microscopy and culture: in 4 patients this visceral mycosis was initially
      diagnosed by the detection of isolated cerebrospinal fluid antigen. Thirty-one
      patients out of 43 suffered from disseminated infection (with positive blood
      cultures and/or antigenemia). The occurrence of clinical relapses, a lethal
      outcome, and time to relapses or to death, did not differ significantly between
      patients with isolated central nervous system and those with disseminated
      cryptococcosis.

PMID- 9642837
TI  - [Modifications in diagnosis and therapy of osteoporosis after bone densitometry].
AB  - The cost-benefit ratio of diagnostic procedures has become a major problem: in
      particular, the expense of computerized bone mineral densitometry for
      osteoporosis diagnosis has brought this issue to public attention. To avoid a
      procedure considered costly, non-specialists often rely on standard radiography
      alone for diagnosis. In this study, we evaluated the percent of cases in which
      densitometry modified diagnosis and therapy based solely on radiographic
      findings. Over a 10-month period, we recruited 133 consecutive post-menopausal
      patients (average age 58.3 years, average time since menopause 12 years) who had
      never undergone densitometry. Bone density at the lumbar (L1-L4) or femoral (non
      dominant) level was measured with dual energy X-ray absorptiometry. The average
      time between densitometry and the last radiographic examination was 13.6 months.
      Ninety-one patients (68.4%) had a change in diagnosis following densitometry. In
      42 cases (31.6%), the previous diagnosis remained unchanged (prevalence ratio
      2.2; 95% confidence interval 1.6 to 2.7). Therapy was changed in 75.2% of the
      cases (100 patients) and remained the same in 24.8% (33 patients; prevalence
      ratio 3.0; 95% confidence interval 2.3 to 3.7). Our data underscore the
      importance of densitometry in yielding quantitative data that are utilizable
      during follow-up and able to support osteoporosis diagnosis and therapy.

PMID- 9642838
TI  - [Effectiveness of long-term ACE-inhibition on pulmonary diffusion and ventilation
      perfusion ratio in chronic heart failure: correlation with physical performance].
AB  - Pulmonary dysfunction contributes to exercise intolerance in patients with
      chronic heart failure, and ACE-inhibition improves the functional capacity of
      these subjects. In this study, we investigated whether and how ACE-inhibitors
      affect pulmonary function and ventilatory response during exercise in chronic
      heart failure. Twenty patients with idiopathic dilated cardiomyopathy and left
      ventricular ejection fraction < 35% underwent pulmonary function tests and
      exercise evaluation with analysis of expired gases before and after 1 year of
      treatment with enalapril (10 mg bid). To explore whether or not the respiratory
      influence of ACE-inhibitors is peculiar to the syndrome of cardiac failure, we
      also studied 19 subjects with mild, untreated primary hypertension who followed
      the same protocol. In this group, enalapril exerted a neutral effect on pulmonary
      function. In chronic heart failure patients, lung volumes were abnormal and did
      not improve after enalapril treatment; on the contrary, alveolar diffusing
      capacity for carbon monoxide increased towards normal values. Exercise tolerance
      time, peak exercise oxygen consumption, ventilation, and tidal volume also
      improved and the dead space to tidal volume ratio was reduced at the peak
      exercise and intermediate exercise phases (20, 60 W). Changes in carbon monoxide
      diffusion were positively correlated to those occurring during peak exercise
      oxygen consumption. A negative correlation was found between the variations in
      oxygen consumption and those in dead space to tidal volume ratio at peak
      exercise. We conclude that in patients with chronic heart failure, ACE-inhibition
      restores diffusing lung properties and improves ventilation-perfusion matching
      during exercise. In this syndrome, sustained reduction in gas exchange resistance
      is a fundamental therapeutic property of this class of drugs.

PMID- 9642839
TI  - [Leukotriene antagonists in the treatment of asthma].
AB  - Bronchial asthma is a chronic inflammatory disease of the airways. Several
      mediators are involved in the inflammatory process, including leukotrienes B4,
      C4, D4 and E4. These compounds promote bronchoconstriction, mucus hypersecretion,
      eosinophil infiltration, monocyte/macrophage activation, and smooth muscle
      proliferation. Two different approaches have been taken to interfere with
      activity: 1) blocking of the specific cysteinyl leukotriene receptor, and 2)
      inhibition of leukotriene biosynthesis (either by inhibition of the primary
      enzyme, 5-lipoxygenase, or its required cofactor 5-lipoxygenase-activating
      protein). Available data suggest that leukotriene modifier therapy is effective
      in several experimental models of bronchial asthma. These agents also have
      demonstrable efficacy in aspirin-induced asthma and against exercise and cold-air
      induced bronchoconstriction. The recent 1997 NHLBI Expert Panel Report II
      Guidelines suggest that leukotriene modifiers may be used as an alternative to
      low dose inhaled corticosteroids in mild persistent asthma. They may also be
      useful in more severe asthma, as supplements to inhaled corticosteroids and long
      acting bronchodilators. The clinical benefit of leukotriene modifier therapy
      occurs early in treatment. However, the response rate for leukotriene modifiers
      approximates 70 to 80% suggesting that there are "responders" as well as "non
      responders" for whom leukotrienes, as inflammatory mediators, may be less
      important. A 2 to 4-week therapeutic trial, with objective monitoring of
      response, may be a reasonable approach to initiating leukotriene modifier
      therapy. Additional controlled trials will be required to define more fully the
      role of these new drugs for long-term control and treatment of asthma.

PMID- 9642840
TI  - [Clinical approach to the hypertensive patient. New guidelines].
AB  - Prospective observational studies clearly show that the risks of stroke, coronary
      artery disease, and premature death are directly related to blood pressure
      levels. Yet as the results of prospective randomized intervention studies have
      indicated, these risks are reduced by effective blood pressure control. Over a 5
      year period, an average reduction of 5-6 mmHg in diastolic blood pressure and of
      10-12 mmHg in systolic blood pressure is associated with a 38% decrease in risk
      of stroke and a 16% decrease in risk of coronary heart disease. Although
      awareness of hypertension has increased markedly, and the number of patients
      treated for this condition has approximately doubled over the last 20 years,
      premature morbidity and mortality remain higher than in the normotensive
      population. This situation may arise from the inadequate level of blood pressure
      control achieved in many patients. Thus, although delineating theoretical rules
      to treat hypertension seems relatively easy, in real life it is not always
      possible to adhere to them. This difficulty highlights the need for appropriate
      guidelines in clinical practice. A number of national groups as well as the World
      Health Organization and the International Society of Hypertension have recently
      published recommendations for the diagnosis and treatment of hypertension.
      Physicians must strive to improve the management of hypertension and remember
      that a thorough clinical evaluation, treatment of associated cardiovascular risk
      factors, prevention of target organ damage, and good patient compliance are key
      elements affecting the success of therapy.

PMID- 9642841
TI  - [Hormone replacement therapy and cardiovascular pathology in menopause].
AB  - Although the incidence of vascular disease increases progressively with age, the
      increment observed in women between 50 and 60 years old does not seem to be
      directly correlated to the menopause. On the other hand, significant
      modifications of some risk factors, particularly those related to lipid
      metabolism and the hemostatic system have been observed in postmenopausal women.
      It should be stressed that the results of these studies, although generally
      concordant, cannot be applied directly to the entire population: the majority of
      women studied were well-educated and from the upper-middle social and economic
      classes and thus more prone to comply with behavioral and therapeutic precepts.
      Moreover, non-white women were excluded from these studies. At present, numerous
      data attest to the beneficial effect of hormone replacement therapy on
      cardiovascular disease in postmenopausal women. The presently running National
      Institutes of Health 9-year randomized primary prevention study (Women's Health
      Initiative) and the secondary prevention "Heart Estrogen/Progestin Replacement
      Study" should, within a few years, provide further and, it is hoped, definitive
      information concerning the utility of hormone replacement therapy for the primary
      and secondary prevention of cardiovascular disease.

PMID- 9642842
TI  - Anaphylactic reaction to oral prednisone: a case report and review of the
      literature.
AB  - Reports of corticosteroid anaphylactic reactions are rare in the medical
      literature. We describe the case of a nonatopic 17-year-old girl with bronchial
      asthma and aspirin intolerance who developed a dramatic anaphylactic reaction to
      oral prednisone. She recovered with shock therapy and intravenous administration
      of diphenhydramine and hydrocortisone. Intradermal testing with a wide range of
      steroid preparations gave positive results to prednisone. No reactions occurred
      to methylprednisolone and hydrocortisone. This case and the brief review of the
      literature which follows emphasize the danger of prednisone administration in
      patients who have asthma and a history of drug intolerance.

PMID- 9642844
TI  - [Patient-centered medicine].
AB  - The dominant model in medical practice today has been defined as the "disease
      centered" model. In the past few years, it has been attacked for oversimplifying
      the problems of illness because it assumes disease to be fully accounted for by
      deviations from the norm of measurable biological variables. This article
      describes a patient-centered model that integrates the traditional understanding
      of disease with each patient's experience of illness. The transformed clinical
      method involves three major changes: 1) new tasks for the consultation: the
      patient-centered method focuses on disease and on four principal dimensions of
      the patients, i.e., their ideas about the illness, their feelings and fears, the
      impact of their problems on their lives, their expectations about what should be
      done; 2) new strategies to obtain these objectives: new interviewing skills and
      communication techniques, e.g., attentive listening; open questions; 3) new modes
      of teaching and learning, e.g., the use of role-playing and videotaping. Research
      has shown that patient-centered medicine enables better clinical results to be
      obtained and is associated with increased patient and physician satisfaction.

PMID- 9642843
TI  - Venous thromboembolism after laparoscopic surgery: two case reports and review of
      the literature.
AB  - Two cases of deep vein thrombosis and pulmonary embolism in patients who had
      undergone laparoscopic surgery (cholecystectomy and inguinal hernioplasty in the
      first and crural hernioplasty in the second) are described. These cases suggest
      that prophylaxis for venous thromboembolism should also be given to patients who
      undergo relatively noninvasive surgery such as laparoscopic intervention. The
      presentation concludes with a review of the last 7 years' literature on this
      topic.

PMID- 9642845
TI  - HIV infection of CD8 lymphocytes: a critical step for the disease?

PMID- 9642846
TI  - A learning model of binge eating: cue reactivity and cue exposure.
AB  - In the present article, a learning model of binge eating is presented. It has
      been hypothesized that, parallel to drug intake, the craving and excessive food
      intake of binge eaters is cue controlled. Research in support of the model is
      reviewed and a series of predictions about clinical and non-clinical issues is
      derived from the model. Amongst other things, the model predicts that binge
      eating might be successfully treated with cue exposure and response prevention.
      Practical issues are discussed and preliminary pilot studies on cue exposure for
      bingers are reviewed.

PMID- 9642847
TI  - The relevance of associative learning pathways in the development of obsessive
      compulsive washing.
AB  - The relevance of associative learning in the development of Obsessive-Compulsive
      Disorder (OCD) was investigated in a group of 23 OCD patients whose main concern
      was washing and 23 age and sex matched control subjects who did not have OCD. OC
      washers completed an origins instrument based on Menzies and Clarke's (1993,
      Behaviour Research and Therapy, 31, 355-365) Origins Questionnaire (OQ) for the
      phobic disorders. Control subjects completed a modified version of this measure
      designed to give a comprehensive picture of their experiences with relevant
      contamination-related stimuli. In general, the results question the relevance of
      associative-learning per se in the development of OC washing. Direct and indirect
      conditioning events were very rare in the OCD group, accounting for less than 13%
      of cases. No significant differences between groups were found in the proportion
      of subjects who knew other OC washers, or had experienced direct associative
      learning events prior to onset. Contrary to expectation, significantly more non
      OCD subjects had experienced vicarious learning events related to dirt and
      washing than OCD subjects. However, of note, associative-learning events that
      took place during episodes of depression were significantly more frequently
      reported in the OCD group than in the control group. Depression appeared to play
      a facilitating role in the associative-learning of OC washing. The implications
      of these findings for theoretical accounts of OCD are discussed.

PMID- 9642848
TI  - No superior perception of hyperventilatory sensations in panic disorder.
AB  - It has been argued that panic disorder patients may be more skilled at detecting
      changes in actual physiology than others. The present study investigated if panic
      patients are better than controls in perceiving sensations produced by light
      hyperventilation. Twelve panic patients and 28 control subjects underwent a
      procedure in which they were exposed 12 times to 1 min of light hyperventilation
      or 1 min of 'placebo' hyperventilation (isocapnia). Differences in sensations
      reported during real hyperventilation were compared to sensations reported during
      'placebo' hyperventilation. Results demonstrated an absence of superior
      perception of hyperventilatory sensations in panic patients.

PMID- 9642849
TI  - Etiology of childhood phobias: current status of Rachman's three pathways theory.
AB  - Despite advances in the assessment and treatment of childhood phobias, little is
      known about their etiology. Rachman has proposed that phobias are acquired
      through three different pathways: direct conditioning, modeling or
      instructions/information. We evaluate the empirical support for Rachman's theory
      in relation to the origins of childhood phobias. Although we find support for
      Rachman's theory, a number of methodological and theoretical issues are
      emphasized. For example, insufficient attention has been given to the reliability
      and validity of retrospective subject reports on the acquisition of childhood
      phobias. Also some findings on the origins of childhood fears and phobias are
      more consistent with a nonassociative account of phobia onset, thus providing an
      interesting challenge to Rachman's theory.

PMID- 9642850
TI  - Detection of negative and positive audience behaviours by socially anxious
      subjects.
AB  - Nineteen subjects high in social anxiety and 20 subjects low in social anxiety
      were asked to give a 5-min speech in front of three audience members. Audience
      members were trained to provide indicators of positive evaluation (e.g., smiles)
      and negative evaluation (e.g. frowns) at irregular intervals during the speech.
      Subjects were instructed to indicate, by depressing one of two buttons, when they
      detected either positive or negative behaviours. Results indicated that subjects
      high in social anxiety were both more accurate at, and had a more liberal
      criterion for, detecting negative audience behaviours while subjects low in
      social anxiety were more accurate at detecting positive audience behaviours.

PMID- 9642851
TI  - Recognition bias for safe faces in panic disorder with agoraphobia.
AB  - Panic patients with agoraphobia were compared with normal controls on tasks of
      face recognition. The subjects were presented with 20 photos, and were required
      to make a judgement of the persons on the photos; shortly afterwards they were
      unexpectedly presented with a recognition task. In the first study, one task was
      to judge whether the persons on the photos were critical or accepting: unlike
      social phobics (Lundh and Ost, 1996b, Behaviour Research and Therapy, 34, 787
      794), panic patients showed no bias for critical vs accepting faces on the
      recognition task. In a secondary study, the task was to judge whether the persons
      on the photos were 'safe' or 'unsafe', i.e. whether they could be relied on if
      the subject would need help in some situation. The results showed a recognition
      bias for safe vs neutral faces in panic patients. The index of recognition bias
      for safe faces correlated with avoidance of feared situations when accompanied by
      others, as measured by the Mobility Inventory. The possibility that memory bias
      in emotional disorders is a function of basic concern, or functional importance,
      rather than positive/negative valence is discussed. The results are also
      discussed in terms of degree of elaboration, exposure duration of the stimuli,
      and the generality of the findings.

PMID- 9642852
TI  - Confirmatory factor analysis of the General Self-Efficacy Scale.
AB  - A confirmatory factor analysis of the factor structure of the adapted General
      Self-Efficacy Scale, created by Sherer et al. (1982) [Psychological Reports, 51,
      663-671], was conducted to assess whether the scale's purported 3 factors
      emerged. The results generally supported the 3-factor model, but a model with 3
      correlated factors and one higher-order factor (general self-efficacy) proved to
      fit the data even better.

PMID- 9642853
TI  - Test of Stice's dual pathway model: dietary restraint and negative affect as
      mediators of bulimic behavior.
AB  - The present study was designed to test whether dietary restraint and negative
      affect mediate the relationship between body dissatisfaction and bulimic
      behavior. Four hundred and twelve female students completed questionnaires which
      measured body dissatisfaction, restrained eating, negative affect and bulimic
      behavior. The results indicated that dietary restraint and negative affect
      partially mediated the relationship between body dissatisfaction and bulimic
      behaviors. The findings are discussed in light of previous research which
      suggests that restraint needs to be viewed as a multidimensional construct.
      Longitudinal studies are now needed to investigate the causal and possible
      bidirectional nature of the interrelationships in the model tested here.

PMID- 9642854
TI  - Glove powder--the call for a ban.

PMID- 9642855
TI  - Research problems in primary care.

PMID- 9642856
TI  - A static diagnosis.

PMID- 9642857
TI  - Amalgam tattoo.

PMID- 9642858
TI  - Scaling the peaks of private practice.

PMID- 9642859
TI  - Anxiety and trauma in the chair.

PMID- 9642860
TI  - Short course to an education plan.

PMID- 9642861
TI  - Toward a standardised information system for dentistry.
AB  - Information technology is growing rapidly in both its capability and capacity to
      support the delivery of health care. This paper describes the work of the Dental
      Interspec project, commissioned by the Department of Health. The aim of the
      project is to provide a framework for the development of information management
      and technology in dentistry. It is hoped that the work of this project can be
      built on to eventually produce integrated information systems which would have
      the potential to improve primary dental care delivery for both patients and
      dentists.

PMID- 9642862
TI  - Anti-retroviral drugs--implications for dental prescribing.
AB  - Many patients with HIV/AIDS are now being treated with two or more drugs to
      reduce HIV viraemia and boost CD4 T-cell counts. Patients are using these drugs
      earlier in the course of their disease and so GDPs are likely to encounter them
      in practice. The drugs have dramatically altered short term prognosis but are
      potent and have potentially serious drug interactions. Some of these drugs have
      interactions with drugs used in the dental care setting and this paper sets out
      to summarise those that are relevant in this area.

PMID- 9642863
TI  - The hollow box maxillary obturator.
AB  - A case is reported assessing the problems encountered after surgical resection of
      the maxilla. The use of a hollow box obturator and details of its construction
      are described. The importance of skin grafting of the maxillary defect and use of
      available anatomical undercuts to optimise support and retention of the obturator
      is stressed. By provision of a lightweight hollow obturator, the weight of the
      prosthesis is kept to a minimum, helping retention, and allowing good resonance
      during speech. Initially the patient was to be assessed for an implant retained
      prosthesis, however, a satisfactory conventional prosthesis met the functional
      and aesthetic needs of the patient and avoided the need for further surgery for
      placement of implants.

PMID- 9642864
TI  - Advances in periodontal diagnosis. 10. Potential markers of bone resorption.
AB  - This paper describes the markers of bone resorption which might serve as
      potential markers for periodontal disease activity. It firstly describes the bone
      specific proteins which are involved in bone mineralisation and the role they
      play in this process. It then explains how they may pass into GCF and reviews
      those studies which have attempted to relate these factors to periodontal disease
      severity and activity. It next discusses the difficulties in isolating and
      detecting these factors in GCF and their possible use as markers for periodontal
      disease activity. As the final part in the series it lastly discusses the
      possible uses of predictive diagnostic tests of periodontal disease activity in
      dental practice.

PMID- 9642865
TI  - Factors related to time management are major job stressors for GDPs.

PMID- 9642866
TI  - Dental treatment for chronically sick children is affected by their medical
      disorder.

PMID- 9642867
TI  - Allergy to local anaesthetic drugs is rare but does occur.

PMID- 9642868
TI  - Perceived sources of occupational stress in general dental practitioners.
AB  - AIM: To evaluate levels of occupational stress in general dental practitioners
      (GDPs) and compare them with those reported by Cooper et al. (1987).
      DESIGN/SETTING: Postal questionnaire in England and Wales. SUBJECTS: A sample of
      1007 GDPs was chosen from the Dental Register. MAIN OUTCOME MEASURES: 30 separate
      stressors were scored on a 5-point scale. Summated scores within time-, job-,
      income-, staff- and patient-related categories were submitted to analysis of
      variance by sex, type of practice, years since qualification and geographic
      location. RESULTS: 823 questionnaires were returned (82%) of which 667 were from
      practising GDPs (63% male, 26% female, 1% undetermined) working full- (87%) or
      part- (13%) time in NHS (61%), private (8%), mixed (26%), or community (5%)
      practice. In general, problems associated with time management were the most
      stressful. The highest ranked individual stressors were 'running behind schedule'
      (percentage responding with scores 4 or 5 = 61.9, 95% confidence intervals = 58.2
      65.6), followed by 'coping with difficult or uncooperative patients' (58.2, 54.5
      61.9) and the 'working constraints set by the NHS' (57.5, 53.8-61.2). Differences
      in levels of reported stress (P < 0.05) were observed for at least one group
      category of stressor between practitioners with different types of practice,
      between males and females, by geographical area (north against south) and by the
      length of time since qualification. CONCLUSIONS: The results indicate that GDPs
      now rank factors related to time management as major job stressors, with an
      apparently dramatic elevation of 'NHS working constraints' to a top-ranking
      stressor since 1986.

PMID- 9642869
TI  - Comprehensive dental treatment of healthy and chronically sick children under
      intubation general anaesthesia during a 5-year period.
AB  - OBJECTIVE: To quantify the number of extractions and/or restorations placed in
      chronically sick children under intubation general anaesthesia and compare these
      findings with healthy children. SETTING: Two large paediatric dentistry units in
      Central London: a tertiary referral centre dealing with severe chronic sickness
      in children and an undergraduate dental school with a large commitment to special
      needs dentistry in children. DESIGN: Prospective comparison of treatment received
      for (a) chronically sick children and (b) dentally anxious (otherwise fit)
      children receiving intubation general anaesthesia during July 1991 to June 1996
      inclusive. The statistical tests used were the Shapiro-Wilks test for normality
      and the Mann Whitney U test for non-parametric comparison of independent groups.
      MAIN OUTCOME MEASURES: Mean total treatment tally (TTT)--the sum of extractions
      and restorations for each child presented as summary data. RESULTS: Different
      patterns of dental care were found between the healthy and chronically sick
      groups. For similar levels of disease, a significantly greater number of
      extractions were carried out for chronically sick children (P < 0.0001), and
      significantly fewer restorations (P < 0.0001). The number of pulpotomies and
      stainless steel crowns provided to sick children was significantly smaller than
      to healthy children (P < 0.0001). This paper discusses the influences of chronic
      ill health on dental treatment provided under general anaesthesia. CONCLUSION:
      The underlying medical disorder in chronically sick children significantly
      influences the pattern of treatment when this is provided under general
      anaesthesia.

PMID- 9642870
TI  - Alleged allergy to local anaesthetic drugs.
AB  - OBJECTIVE: To identify the true nature of an acute reaction in 25 patients
      initially diagnosed as allergic to local anaesthetic drugs. SETTING: University
      General and Dental Hospitals. INTERVENTIONS: Detailed review of each patient's
      previous exposure to local anaesthetic drugs and of the history of the acute
      event was followed up with challenge testing by intradermal injection. RESULTS:
      One patient was subsequently found to be genuinely allergic to a local
      anaesthetic drug of the amide type. A wide range of conditions had actually
      precipitated the other adverse reactions, but all could be classified under three
      major headings: an immunological condition to a different antigen; a
      manifestation of anxiety; or an iatrogenic problem. CONCLUSION: Local anaesthetic
      allergy is rare, but does occur. All reactions to local anaesthetic drugs must be
      assessed carefully and specialist referral may be appropriate.

PMID- 9642871
TI  - The end of the dentist's drill.

PMID- 9642872
TI  - [Campylobacter jejuni colitis and Guillain-Barre syndrome].

PMID- 9642873
TI  - Doppler velocimetry in the umbilical and middle cerebral arteries in fetuses with
      intrauterine growth retardation or fetal distress.
AB  - To clarify the usefulness of Doppler velocimetry in high-risk fetuses, i.e. with
      intrauterine growth retardation (IUGR) or with fetal distress, nomograms of the
      age-related changes in resistance and pulsatility indices in the fetal umbilical
      and middle cerebral arteries were made, and the best cut-off values for each
      parameter were determined. Included were 505 and 684 fetuses as the control and
      subject groups, respectively, between 22 and 41 weeks' gestation. Using the color
      coded pulsed Doppler method, the resistance index in the umbilical and middle
      cerebral artery (RIUA, RIMCA), the pulsatility index in both these arteries
      (PIUA, PIMCA), and the RI and PI ratios between these arteries (RIUA/MCA,
      PIUA/MCA) were measured. In normal fetuses, RIUA and PIUA showed a gradual
      decrease with advance in gestational age. RIMCA and PIMCA showed a parabolic
      fashion with a peak around 30-31 weeks' gestation. RIUA/MCA and PIUA/MCA ratios
      decreased until 30-31 weeks' gestation and then increased to term. Analyses with
      receiver-operating-characteristic (ROC) curves revealed that PIUA is the most
      appropriate parameter in identifying IUGR under the cut-off point of 1.5 S.D.,
      with a sensitivity, specificity, positive and negative predictive value, and
      accuracy of 60.6%, 93.3%, 75.2%, 87.6%, and 85.0%, respectively. As for fetal
      distress, the PIUA/MCA ratio was the most efficacious parameter under the cut-off
      point of 2.0 S.D., with a sensitivity, specificity, positive and negative
      predictive value, and accuracy of 67.3%, 97.4%, 72.9%, 96.7% and 94.6%,
      respectively. The findings obtained indicate that the measurement of PI value in
      the umbilical artery is enough to detect IUGR per se, probably due to the
      reflection of the decrease in the placental vascular bed, and that the ratio of
      indices between the umbilical artery and middle cerebral artery is more accurate
      than independent evaluations in identifying fetuses developing fetal distress,
      reflecting a brain sparing effect as well as fetoplacental insufficiency.

PMID- 9642874
TI  - Indirect measurement of end-diastolic pressure-volume relation in the in situ
      canine heart.
AB  - We developed a new method to estimate the end-diastolic pressure-volume relation
      (EDPVR) of the ejecting ventricle without directly measuring the ventricular
      volume. The following equation is derived from the ventricular elastance concept;
      Pes = Ees (Ved-Vo-Vj), where Pes is end-systolic pressure; Ees, end-systolic
      elastance; Ved, end-diastolic volume; Vo, an empirical constant; and Vj, ejected
      volume at end-systole. Therefore, under a constant preload and contractility; two
      sets of Pes and Vj, i.e, (Pes 1, Vj 1) and (Pes 2, Vj 2), yield an equation of Ve
      = (Pes 1 Vj 2-Pes 2 Vj 1)/(Pes 1-Pes 2), where Ve is effective end-diastolic
      volume, Ved-Vo. Repeated measurements of Ve under various levels of end-diastolic
      pressure (Ped) allow us to determine the EDPVR. In 8 anesthetized dogs with the
      chest open, we obtained two sets of Pes and Vj under a given Ped as mentioned
      above, one in a normally ejecting condition and the other in a clamping condition
      of the descending aorta to increase afterload of the left ventricle. We then
      calculated the Ve from the equation mentioned above. We repeatedly determined the
      Ve varying preload levels to obtain the EDPVR. We compared the EDPVR estimated by
      the present method with that directly measured by the balloon method in the
      arrested ventricle. These two EDPVRs were correlated very well. To compare more
      quantitatively, the chamber stiffness constant was obtained. The chamber
      stiffness constant derived from the estimated EDPVR was linearily related to that
      derived from the directly measured EDPVR (y = 1.043x + 0.003, r = 0.987).
      Furthermore, in order to test whether the EDPVR derived from our present method
      can detect changes in left ventricular compliance in the in situ ventricle, we
      obtained the EDPVRs under the three different (intact, opened, and closed)
      conditions of the pericardium in six dogs. The EDPVR was shifted upward in the
      closed condition compared with that in the intact condition, while it was shifted
      downward in the opened condition. Thus, the changes of the left ventricular
      diastolic compliance were correctly evaluated by the developed method. Therefore,
      we conclude that the EDPVR obtained using our indirect method is reliable to
      estimate the ventricular diastolic properties of the in situ heart.

PMID- 9642875
TI  - The canine alkaline phosphatases: a review of the isoenzymes in serum, analytical
      methods and their diagnostic application.
AB  - This paper reviews the alkaline phosphatases in canine serum, the analytical
      methods used for qualitative and/or quantitative detection of these isoenzymes,
      and the diagnostic significancy of each of these isoenzymes. The paper further
      describes some of the latest advances in our knowledge of the canine alkaline
      phosphatases and possible areas of future research.

PMID- 9642876
TI  - In vitro viability of mouse oocytes vitrified in an ethylene glycol-based
      solution.
AB  - Ovulated mouse oocytes denuded of their cumulus cells, were vitrified in a
      solution containing 7 M ethylene glycol as the sole cryoprotectant using one or
      two steps of exposure before vitrification and were diluted in 1 M sucrose
      solution in 5 or 10 min after warming. The results proved that the viability of
      oocytes are detrimentally affected by exposure to the vitrification solution even
      without vitrification. At 5 min dilution time, the two-step exposure was superior
      to the one-step in terms of the post-warming recovery rate of vitrified oocytes
      with normal morphology and their subsequent development to the blastocyst stage
      (p < 0.01) after fertilization in vitro. At 10 min dilution time, no significant
      difference between one- or two-step exposure was found. The effect of the
      addition of 0.5 M sucrose to the vitrification solution was also determined and
      did not result in a significant improvement in the viability of oocytes vitrified
      in one-step and diluted for 10 min. In conclusion, the results in this study
      indicate that oocytes can be vitrified with 7 M ethylene glycol as the sole
      cryoprotectant in the vitrification solution, and that the recovery of normal
      oocytes after one-step exposure in the vitrification solution can be improved by
      10 min dilution time. However, the improvement in the recovery rate of oocytes
      with normal morphology and their subsequent developmental in vitro was not
      improved by the addition of 0.5 M sucrose to the vitrification solution.

PMID- 9642877
TI  - Differentiative potential of a mouse parthenogenetic embryonic stem cell line
      revealed by embryoid body formation in vitro.
AB  - The in vitro differentiative potential of mouse parthenogenetic (PG) embryonic
      stem (PGES) cells were investigated in the formation of embryoid bodies (EBs).
      EBs derived from PGES cells retarded in growth and showed restricted
      differentiation compared to their fertilized counterpart. In chimeric EBs from
      the aggregation of PGES and fertilized ES cells, morphological examination
      revealed that PGES cells were reduced in their population and distributed in
      endodermal layer as culture periods proceeded. These findings were comparable to
      those in aggregation chimeras of fertilized and PG embryos, and suggest that the
      differentiation of PGES cells in vitro is restricted in the formation of EBs.

PMID- 9642878
TI  - Trisomy 8 does not affect differentiative potential in a murine parthenogenetic
      embryonic stem cell line.
AB  - Murine parthenogenetic embryonic stem (ES) cell lines expressing lac Z reporter
      gene were isolated after co-transfection with lac Z reporter gene (pENL) and neo
      gene (pSTneo) to TMA-48P cell line of 129/Sv origin. Karyotype analyses showed
      that all of four transfected cell lines examined contained 41 chromosomes with
      trisomy 8. Bacterial neo transgene required for G418 selection were integrated
      into several chromosomes including chromosome 8. Histological studies of
      teratomas formed in syngenic mice and embryoid bodies grown in vitro showed that
      the differentiative potential remained almost identical in chromosomally normal
      parental cell line and its derivative cell lines trisomic for chromosome 8.

PMID- 9642880
TI  - Publications by the staff of the Graduate School of Veterinary Medicine.

PMID- 9642879
TI  - An introduction of the four departments composing the Graduate School of
      Veterinary Medicine, Hokkaido University.

PMID- 9642883
TI  - A longitudinal look at the relation between depression and anxiety in children
      and adolescents.
AB  - Elementary school students (n = 330) and their parents (n = 228) participated in
      a 3-year longitudinal study of the temporal relation between anxiety and
      depressive symptoms in children. Every 6 months, children and parents completed
      depression and anxiety questionnaires for a total of 6 waves. Structural equation
      modeling revealed that individual differences on all measures were remarkably
      stable over time. Nevertheless, high levels of anxiety symptoms at 1 point in
      time predicted high levels of depressive symptoms at subsequent points in time
      even after controlling for prior levels of depression symptoms. These findings
      were consistent across self- and parent reports. Results support the temporal
      hypothesis that anxiety leads to depression in children and adolescents.

PMID- 9642884
TI  - Why are depression and anxiety correlated? A test of the tripartite model.
AB  - L. A. Clark and D. Watson's (1991) tripartite model groups the symptoms of
      depression and anxiety into 3 components: nonspecific symptoms of general
      distress, which do not distinguish depression and anxiety; physiologic arousal,
      which is relatively unique to anxiety; and anhedonia (or low positive affect),
      which is unique to depression. Structural equation modeling was used to test this
      model with self-report data from 3 different samples: outpatients seeking
      treatment for mood disorder, anxiety disorder, or both (n = 483) outpatients
      seeking treatment for substance abuse (n = 453), and college students (n = 516).
      The tripartite model did not fit any of the sample covariance matrices, because
      the nonspecific symptoms of depression and anxiety could not be adequately
      represented by a single General Distress factor. An alternative model, in which
      the Anhedonia and Nonspecific Depression factors loaded on a second-order
      Depression factor, while the Somatic Arousal and Nonspecific Anxiety factors
      loaded on a second-order Anxiety factor, produced an excellent fit in all the
      groups. The Nonspecific Depression and Nonspecific Anxiety factors were the most
      valid and specific indicators of depression and anxiety, respectively. Anhedonia
      and Somatic Arousal were significantly less valid measures of depression and
      anxiety. The implications of these findings are discussed.

PMID- 9642885
TI  - Temporal progression of alcohol dependence symptoms in the U.S. household
      population: results from the National Comorbidity Survey.
AB  - General population data are presented on patterns and predictors of temporal
      progression of alcohol dependence symptoms in the general population. The data
      come from the National Comorbidity Survey, a nationally representative general
      population survey of respondents ages 15-54. Lifetime symptom classes were
      estimated with latent class analysis (LCA). A 4-class LCA solution, including a
      1st asymptomatic class and 3 progressively more serious symptomatic classes, was
      found to fit the data. Probability of initial symptom onset among drinkers was
      found to be highest in the 10-24 age range, to be higher among men than women,
      and to have increased dramatically in the past 4 decades. Age, gender, and cohort
      effects were less powerful in predicting symptom progression. A narrowing of the
      gender difference over time was due largely to a convergence in initial symptom
      onset among men and women ages 10-24. These results suggest that a rise in
      initial problems was more important than an increase in the transition from
      problems to dependence in accounting for the growing prevalence of alcohol
      dependence during the post-World War II years in the United States.

PMID- 9642886
TI  - Training in cognitive, supportive-expressive, and drug counseling therapies for
      cocaine dependence.
AB  - This study assessed the effects of training on the performance of 65 therapists
      in delivering manual-guided therapies to 202 cocaine-dependent patients. Changes
      in ratings of therapists' adherence and competence was assessed in 3 treatment
      modalities: supportive-expressive dynamic therapy (SE), cognitive therapy (CT),
      and individual drug counseling. Effects of manual-guided training on the
      therapeutic alliance were also assessed. Training effects were examined through a
      hierarchical linear modeling approach that examined changes both within cases and
      across training cases. A large effect across cases was detected for training in
      CT. Supportive-expressive therapists and individual drug counselors demonstrated
      statistically significant learning trends over sessions but not over training
      cases. Training in SE and CT did not have a negative impact on the therapeutic
      alliance, although alliance scores for trainees in drug counseling initially
      decreased but then rebounded to initial levels.

PMID- 9642887
TI  - Trauma and posttraumatic stress disorder in severe mental illness.
AB  - This research assessed the lifetime prevalence of traumatic events and current
      posttraumatic stress disorder (PTSD) in 275 patients with severe mental illness
      (e.g., schizophrenia and bipolar disorder) receiving public mental health
      services in Concord and Manchester, New Hampshire, and Baltimore, Maryland.
      Lifetime exposure to traumatic events was high, with 98% of the sample reporting
      exposure to at least 1 traumatic event. The rate of PTSD in our sample was 43%,
      but only 3 of 119 patients with PTSD (2%) had this diagnosis in their charts.
      PTSD was predicted most strongly by the number of different types of trauma,
      followed by childhood sexual abuse. The findings suggest that PTSD is a common
      comorbid disorder in severe mental illness that is frequently overlooked in
      mental health settings.

PMID- 9642888
TI  - Autobiographical memory in acute stress disorder.
AB  - Survivors of motor vehicle accidents with acute stress disorder (ASD) or with no
      ASD participated in a study on autobiographical memory within a week of their
      trauma. In Experiment 1, participants were provided cue words to elicit
      autobiographical memories of both an unconstrained time period and their trauma.
      Participants with ASD reported fewer specific memories to positive cue words than
      did non-ASD participants, even when the influence of depression was controlled.
      In Experiment 2, the same participants were assessed for posttraumatic stress
      disorder (PTSD) 6 months posttrauma. Poor recall of specific memories of the
      trauma in Experiment 1 accounted for 25% of the variance of PTSD severity.
      Accessibility of trauma memories in the acute posttrauma phase may have
      significant implications for longer term adjustment.

PMID- 9642889
TI  - The relationship between acute stress disorder and posttraumatic stress disorder:
      a prospective evaluation of motor vehicle accident survivors.
AB  - Motor vehicle accident survivors (n = 92) were assessed for acute stress disorder
      (ASD) within 1 month of the trauma and reassessed (n = 71) for posttraumatic
      stress disorder (PTSD) 6 months posttrauma. ASD was diagnosed in 13% of
      participants, and a further 21% had subclinical levels of ASD. At follow-up, 78%
      of ASD participants and 60% of subclinical ASD participants met criteria for
      PTSD. The strong predictive power of acute numbing, depersonalization, a sense of
      relieving the trauma, and motor restlessness, in contrast to the low to moderate
      predictive power of other symptoms, indicates that only a subset of ASD symptoms
      is strongly related to the development of chronic PTSD. Although these findings
      support the use of the ASD diagnosis, they suggest that the dissociative and
      arousal clusters may require revision.

PMID- 9642890
TI  - The Family Health Project: psychosocial adjustment of children whose mothers are
      HIV infected.
AB  - The psychosocial adjustment of 87 inner-city African American children 6-11 years
      old whose mothers were HIV infected was compared with that of 149 children from a
      similar sociodemographic background whose mothers did not report being HIV
      infected. Children were not identified as being HIV infected. Mother reports,
      child reports, and standardized reading achievement scores were used to assess 4
      domains of adjustment: externalizing problems, internalizing problems, cognitive
      competence, and prosocial competence. The results indicated that, on average,
      children from both groups had elevated levels of behavior problem scores and low
      reading achievement scores when compared with national averages. Relative to
      children whose mothers were not infected, those whose mothers were HIV infected
      were reported to have more difficulties in all domains of psychosocial
      adjustment. Potential family processes that may explain the findings are
      discussed.

PMID- 9642891
TI  - Trajectories of adaptation in pediatric chronic illness: the importance of the
      individual.
AB  - This study used individual growth modeling to examine individual difference and
      group difference models of adaptation. The adaptation of 27 children with
      juvenile rheumatoid arthritis (JRA) and 40 children with insulin-dependent
      diabetes mellitus (IDDM) was tracked for 18 months from diagnosis. A control
      group of 62 healthy children was followed over the same time period. Clustering
      procedures indicated that child and family adaptation could be described by a
      number of distinct adaptation trajectories, independent of diagnostic group
      membership. In contrast, parental adaptation trajectory was associated with
      diagnostic group membership and control over disease activity for the JRA group
      and with diagnostic group membership for healthy controls. The observation of
      common patterns across trajectory sets, as well as the finding that trajectories
      were differentially related to a number of variables of interest, support the use
      of trajectories to represent adaptation to chronic disease.

PMID- 9642892
TI  - Factors that mediate and moderate the link between partner abuse and suicidal
      behavior in African American women.
AB  - Findings from a study comparing partner abuse in African American women suicide
      attempters (n = 148) and nonattempters (n = 137) revealed higher rates of
      physical and nonphysical partner abuse among attempters than their
      demographically similar nonsuicidal counterparts. The partner abuse--suicidal
      behavior link was mediated by psychological distress, hopelessness, and drug use
      and moderated by social support. Results also revealed that nonphysical partner
      abuse accounted for unique variance in the prediction of suicide attempt status
      beyond that attributable to childhood maltreatment. Implications of the findings
      for assessing both suicidal and abused women are discussed, and recommendations
      for preventive interventions for women at risk for suicidal behavior are
      provided.

PMID- 9642893
TI  - The community reinforcement approach with homeless alcohol-dependent individuals.
AB  - Homeless alcohol-dependent individuals were randomly assigned to receive either a
      behavioral intervention (i.e., the Community Reinforcement Approach [CRA]) or the
      standard treatment (STD) at a large day shelter. Ninety-one men and 15 women
      participated. The majority of participants were White (64%), but both Hispanic
      (19%) and Native American (13%) individuals were represented as well. Overall,
      the decline in drinking levels from intake through follow-ups was significant. As
      predicted, CRA participants significantly outperformed STD group members on
      drinking measures across the 5 follow-ups, which ranged from 2 months to 1 year
      after intake. Both conditions showed marked improvement in employment and housing
      stability.

PMID- 9642894
TI  - Tailored interventions to communicate stage-matched information to smokers in
      different motivational stages.
AB  - Smokers in stages of low readiness to quit (immotives and precontemplators) and
      smokers in stages of high readiness to quit (contemplators and preparers) were
      randomly allocated to 1 of 4 tailored intervention conditions offering outcome
      information, self-efficacy-enhancing information, both sorts of information, or
      no information. Data on 1,540 smokers, stratified by stage, were analyzed. The
      primary outcome measure was stage transition. The hypotheses with regard to stage
      matched information for immotives and precontemplators were not verified. With
      regard to contemplators and preparers, the following was found: Compared with the
      control group, contemplators benefited the most from both sorts of information,
      whereas preparers benefited the most from self-efficacy-enhancing information
      only. Comparisons between contemplators and preparers who were assigned to the
      matched treatment and contemplators and preparers who were assigned to the
      mismatched treatment supported these findings.

PMID- 9642895
TI  - Interpretive and supportive forms of psychotherapy and patient personality
      variables.
AB  - A randomized clinical trial investigated the efficacy of interpretive and
      supportive forms of short-term individual psychotherapy and the interaction of
      each form with the patient's quality of object relations (QOR) and psychological
      mindedness (PM). The psychiatric outpatient sample included 144 therapy
      completers and 27 dropouts. Eight experienced therapists provided distinct forms
      of manual-guided therapy. Outcome was assessed by a comprehensive battery. The
      dropout rate was higher for interpretive therapy than for supportive therapy.
      Patients in both forms improved, but they did not differ on outcome from each
      other. A multivariate interaction effect indicated a direct relation between QOR
      and outcome for interpretive therapy and almost no relation for supportive
      therapy. A multivariate main effect indicated a direct relation between PM and
      outcome for both forms. The relevance of patient personality to outcome in
      different forms of therapy is addressed.

PMID- 9642896
TI  - Psychopathology associated with sexual abuse: the importance of complementary
      designs and common ground.
AB  - In their recent longitudinal study of youth victimization and consequent
      traumatization, S. Boney-McCoy and D. Finkelhor (1996) contrast their position
      with previous retrospective research (S. Harter, P. Alexander, & R. A. Neimeyer,
      1988; M. R. Nash, T. C. Hulsey, M. C. Sexton, T. L. Harralson, & W. Lambert,
      1993a), arguing that their data support the impact of victimization per se,
      independent of the moderating effect of family environment. Because Boney-McCoy
      and Finkelhor's argument may misrepresent the results of such studies, this
      article (a) clarifies the actual findings of previous retrospective studies of
      abuse, (b) suggests methodological limitations both in Boney-McCoy and
      Finkelhor's research and in that of S. Harter et al., 1998, and M. R. Nash et
      al., 1993a, that should be remedied by future investigators, and (c) argues that
      both retrospective clinical research and prospective community surveys converge
      on a common ground, namely, that specific abuse experiences can best be
      understood and investigated in the context of the prior, contemporaneous, and
      subsequent family environments in which they occur.

PMID- 9642898
TI  - Brief motivational interviewing in a hospital setting for adolescent smoking: a
      preliminary study.
AB  - This study tested the feasibility and efficacy of a brief smoking intervention
      for adolescents in a hospital setting. Forty adolescent patients were randomized
      to receive either brief advice or a motivational interview, a nonconfrontational
      therapeutic intervention. Feasibility of brief smoking interventions with teen
      patients was supported by high rates of recruitment, retention, and quit
      attempts, and long periods of continuous abstinence. Although between-groups
      differences on smoking measures were not significant at 3-month follow-up, an
      effect size of h = .28 was noted. The sample showed significant decreases in
      smoking dependence and number of days smoked. Baseline stage of change, smoking
      rate, and depression were significant prospective predictors of smoking outcome.
      Implications for smoking intervention research with adolescents are discussed.

PMID- 9642899
TI  - Age and drinking-related differences in the memory organization of alcohol
      expectancies in 3rd-, 6th-, 9th-, and 12th-grade children.
AB  - To advance the theoretical modeling of the development of alcohol expectancies as
      a parallel processing memory network, this study assessed expectancies and
      alcohol consumption of 2,324 children in Grades 3, 6, 9, and 12 from a large
      suburban-rural school district. Individual-differences scaling (INDSCAL), a
      variant of multidimensional scaling, mapped expectancies into a hypothetical
      memory network format, and preference mapping (PREFMAP) modeled hypothetical
      paths of association within this network. Throughout this age range, older and
      higher drinking youth appeared to associate positive and arousing effects with
      alcohol cues, in contrast to lower drinking children, who appeared to mainly
      associate undesirable effects. These drinking-related differences in the
      organization of expectancy information are discernible well before onset of
      regular drinking habits and may influence the development of drinking in
      adolescence.

PMID- 9642900
TI  - Posttraumatic stress disorder after treatment for breast cancer: prevalence of
      diagnosis and use of the PTSD Checklist-Civilian Version (PCL-C) as a screening
      instrument.
AB  - The presence of a posttraumatic stress disorder (PTSD) diagnosis in women (n =
      82) diagnosed with Stage 0-IIIA breast cancer was assessed 6 to 72 months after
      cancer therapy. The PTSD Checklist-Civilian Version (PCL-C) and the PTSD module
      for the Structured Clinical Interview for DSM-IV, Nonpatient Version, PTSD module
      (SCID-NP-PTSD) were administered in a telephone interview. SCID-NP-PTSD results
      indicated prevalence rates of 6% and 4% for current and lifetime PTSD,
      respectively. Use of the recommended cutoff score of 50 on the PCL-C to determine
      diagnosis of current cancer-related PTSD resulted in a sensitivity of .60 and a
      specificity of .99 with 2 false-negative diagnoses. In conclusion, PTSD can be
      precipitated by diagnosis and treatment of breast cancer, and the PCL-C can be a
      cost-effective screening tool for this disorder.

PMID- 9642901
TI  - Neighborhood social context and racial differences in women's heart disease
      mortality.
AB  - Compared to white women, black women experience similar rates of heart disease
      morbidity, but higher rates of heart disease mortality. This puzzling
      relationship may be due to several factors working at varied levels to affect
      each race. For example, the high heart disease mortality rate may be due to
      individual health or socioeconomic risk factors or to social structural factors.
      We conduct a multi-level analysis to address these issues, using data from a
      newly released data file that links the National Health Interview Survey with
      death certificate information from the National Death Index, and with additional
      community level data from the 1990 Census STF-3A files. We are primarily
      interested in the effects of female-headship rates in the census tracts on
      coronary heart disease mortality (CHD) among black and white women. We find that
      women who live in communities with high concentrations of female-headed families
      are more likely to die of heart disease, net of other characteristics. For
      younger women, the effect appears to be routed primarily through poverty whereas
      for older women the effect of female-headship rates remains, net of other census
      tract characteristics. This study, then, highlights the importance of examining
      the effect of neighborhoods and their social content on mortality.

PMID- 9642902
TI  - Athletic participation and sexual behavior in adolescents: the different worlds
      of boys and girls.
AB  - Using multivariate analysis of covariance to test hypotheses about the effects of
      sports and sexual behavior on a sample of 611 Western New York adolescents, this
      study concludes that athletic participation and gender interact to influence
      adolescent sexual outcomes. Female athletes report significantly lower rates of
      sexual activity than female nonathletes; male athletes report slightly (though
      not significantly) higher rates than male nonathletes. The gender-specific effect
      of sports on sexual behavior remains, net of the impacts of race, age,
      socioeconomic status, quality of family relations, and participation in other
      extracurricular activities. This paper introduces cultural resource theory to
      explain how athletic participation influences both traditional cultural scripts
      and exchange resources, which, in turn, condition the sexual bargaining process
      and its outcomes for adolescents.

PMID- 9642903
TI  - How the negative and positive aspects of partner relationships affect the mental
      health of young married people.
AB  - The relationship between marriage and positive mental health is one of the most
      established findings in the stress literature. Few studies, however, examine the
      problematic as well as the supportive impacts of marriage on mental health. This
      paper uses a cohort of young adults who were sampled at 18, 21, or 24 years of
      age and resampled seven years later when they were married at 25, 28, or 31. It
      examines what factors are associated with the quality of marital relationships,
      the relative impact of and balance between negative and positive partner
      relationships on mental health, and sex differences in the determinants and
      outcomes of marital quality. The results indicate that the structural strains of
      parenthood and financial need and their interaction predict problematic and
      supportive spousal relationships and the difference in the levels of these two
      relationships. Problematic relationships with spouses have considerably stronger
      impacts than supportive relationships on depression. However, the difference
      between the amounts of supportive and problematic relationships with spouses has
      a greater impact on mental health than levels of either considered separately.
      Finally, relational quality has a greater impact on the mental health of wives
      than husbands. These findings indicate the importance of considering how marriage
      affects mental health in complex, rather than in straightforward, ways.

PMID- 9642904
TI  - Sources and determinants of social support for caregivers of persons with AIDS.
AB  - This study examines the determinants of social support among a sample of 642
      caregivers of persons with AIDS living in San Francisco and Los Angeles.
      Respondents include both traditional family caregivers (mothers, spouses, other
      relatives) and non-traditional caregivers (friends, homosexual partners).
      Multiple regression analyses are conducted to assess the independent effects of
      six sets of variables on emotional and instrumental support: social-structural
      factors (age, education, employment status), caregiver's relationship to the
      person with AIDS, situational variables (caregiver's HIV status, patient's
      functional disability, interpersonal conflict), social network factors (contact
      with family, contact with friends, community integration), personal resources
      (mastery, caregiving competence), and use of formal community services (patient
      directed services, caregiver-directed services). A number of factors and
      conditions appear to be relevant for caregiver support. For example, results
      indicate that network factors, including frequency of contact, conflict, and
      community integration, are importantly related to caregivers' perceptions of
      emotional support. There is also a trend suggesting lower emotional support among
      traditional family caregivers, relative to nonfamily caregivers, within gender
      categories. With respect to instrumental assistance with caregiving, factors that
      place greater demands and time constraints on caregivers, such as being employed
      and caring for an AIDS patient with greater functional limitations, appear to
      increase the level of informal instrumental support the caregiver receives.
      Partners and spouses, however, receive significantly lower instrumental
      assistance, independent of other factors. Implications of the findings are
      discussed.

PMID- 9642905
TI  - Relative income expectations, expected malpractice premium costs, and other
      determinants of physician specialty choice.
AB  - We analyze the effects of relative income expectations, expected malpractice
      premium cost, and other economic and noneconomic factors on physician specialty
      choice. The data for this paper are taken from responses of medical students who
      completed the Association of American Medical Colleges' Medical School
      Questionnaire and graduated from medical school in 1995. A random utility model
      is used to guide our thinking; the econometric technique is multinomial logit
      regression. Selection of a surgical or support specialty is found to be
      positively income motivated, while the influence of expected relative income is
      negatively related to the choice of primary-care and medical practices. Concern
      over malpractice premium cost is negatively related to surgical and positively
      related to primary-care selection. Other important determinants of choice are
      planned location of practice, length of residency, type of medical school
      attended, score on the science problems section of the Medical College Admission
      Test, predictable working hours and perceived prestige of the specialty. Policies
      that alter expected relative income, length of residency, desired location of
      practice, medical school attended, predictable working hours, and prestige of
      practice, rather than financial aid, may be appropriate for correcting a
      perceived maldistribution of physicians among specialties.

PMID- 9642906
TI  - Variability of the center of pressure pattern integral during walking.
AB  - The objective of this study was to measure the between-trial variability of the
      center of pressure pattern integral (COPPI) at the shoe-floor interface and
      within the shoe. Ten trials of the COPPI were recorded simultaneously at the shoe
      floor interface and within the shoe as ten subjects walked over ground in
      standardized footwear and with two types of foot orthoses. While the results
      showed that the within-shoe shoe-only and soft orthoses conditions caused the
      greatest decrease in the COPPI, it was extremely inconsistent-between trials,
      whether measured at the shoe-floor interface or within the shoe. This suggests
      that the COPPI is not an acceptable method of assessing the effectiveness of foot
      orthoses.

PMID- 9642907
TI  - Foot and ankle injuries among martial artists. Results of a survey.
AB  - The practice of the martial arts is associated with a variety of lower-extremity
      injuries. Previous studies of the martial arts have examined injuries to the
      entire body, while providing only limited information on trauma to the foot and
      ankle. After a comprehensive review of the literature on martial arts injuries,
      the authors report the results of a survey on foot and ankle injuries sustained
      by martial arts practitioners.

PMID- 9642908
TI  - Review of the Dockery procedure for lateral ankle instability. A seven-year
      retrospective analysis.
AB  - This article presents a critical review of the Dockery procedure (autogenous
      peroneus longus free graft technique) for the treatment of lateral ankle
      instability. Those patients with gastrocnemius equinus were treated with
      gastrocnemius recession during surgery. The authors reviewed 33 stabilizations
      performed over a period of 7 years to analyze the effectiveness of the procedure
      with and without the addition of the gastrocnemius recession. Assessed were the
      type and length of conservative therapy, the time to return to regular activity,
      complications experienced, and the recurrence rate. The results show a reinjury
      rate of 3%. The complications included infection, prolonged healing, and
      occasional screw irritation requiring screw removal. In light of the low
      incidence of reinjury, this technique is a valid procedure for treating lateral
      ankle instability.

PMID- 9642909
TI  - Biomechanics of the foot in diabetes mellitus. Some theoretical considerations.
AB  - Although diabetes mellitus is a biochemical disease, it has biomechanical
      consequences for the lower extremity. Numerous alterations occur in the function
      of the foot and lower extremity in people with diabetes. This article evaluates
      biomechanical alterations of the foot in the presence of neuropathy in patients
      with diabetes in the context of several theoretical concepts. Further study of
      these hypotheses will result in a better understanding of how diabetes causes
      elevated plantar pressures and the potential of strategies to prevent these
      changes so that the burden of diabetic foot disease can be reduced.

PMID- 9642910
TI  - Review of radiographic measurements following Austin bunionectomy.
AB  - This study compared preoperative and postoperative results for selected
      radiographic measurements of 30 patients undergoing the modified Austin
      bunionectomy procedure for the correction of hallux abducto valgus. Significant
      reductions in all postoperative radiographic values were demonstrated, including
      hallux abductus angle, metatarsus primus adductus angle, tibial sesamoid
      position, and first metatarsal protrusion distance.

PMID- 9642911
TI  - Tarsal coalition in an adult with cavovarus feet.
AB  - Symptomatic tarsal coalition is often considered to be synonymous with peroneal
      spastic flatfoot. The association of the cavovarus foot type with tarsal
      coalition is less well established and has been described only in children. This
      article describes a case of an adult female with symptomatic cavovarus feet with
      talocalcaneal coalition. The authors theorize about the pathology of muscle spasm
      and pain in patients with this condition.

PMID- 9642912
TI  - The Ogden Anchor.
AB  - Many procedures performed by podiatric surgeons today require the use of a soft
      tissue anchoring device. In recent years, many new anchoring devices have become
      available for use in the foot and ankle. The authors introduce a new soft-tissue
      anchoring device that has yet to be described in the podiatric literature and
      present two cases in which the new anchor was used.

PMID- 9642913
TI  - Emergence of non-group A streptococcal necrotizing diabetic foot infections.
AB  - Recently the authors have noted a disturbing trend toward an increased incidence
      of necrotizing infections caused by non-group A streptococcal species. This
      article describes the typical clinical course of such an infection. Prompt
      surgical intervention, coupled with an antibiotic regimen aimed at mitigating
      exotoxin release, may be both limb- and life-preserving.

PMID- 9642914
TI  - Vietnamese military shoes then and now.

PMID- 9642915
TI  - Complication encountered with self-monitoring of blood glucose levels.

PMID- 9642916
TI  - Tibial nerve entrapment and heel pain caused by a Baker's cyst.

PMID- 9642917
TI  - The lateral chest radiograph in the detection of pericardial effusion: a
      reevaluation.
AB  - The purpose of this study was to evaluate the usefulness of 10 previously
      published plain film signs for diagnosing pericardial effusion and to determine
      whether the posteroanterior (PA) or lateral chest radiograph was the better view
      for detecting pericardial effusion. A retrospective study of 100 consecutive
      adult patients with pericardial effusions confirmed by echocardiography and/or
      computed tomography was undertaken. Five signs were found to be useful in
      detecting pericardial effusion on plain films, and the lateral chest radiograph
      was found to be better than the PA view in detecting pericardial effusion. The
      water-bottle configuration, widening of the carinal angle, and the differential
      density sign were helpful in diagnosing pericardial effusion on the PA view.
      However, these signs were only seen in moderate-to-large effusions. The displaced
      epicardial fat pad sign and the posteroinferior bulge sign on the lateral view
      improved the detection of moderate-to-large pericardial effusions, and were also
      present in many of the cases with small pericardial effusions. Recognition of
      specific signs of pericardial effusion on the lateral chest radiograph may
      significantly improve the plain film detection of pericardial effusion.

PMID- 9642918
TI  - Bronchial foreign bodies simulating endobronchial malignancy.
AB  - Reported are two cases of benign endobronchial lesions with granulomatous
      reactions that led to complete airway obstruction. Combined with a long history
      of cigarette smoking and the appearance of a hilar mass, these lesions appeared
      clinically to be bronchogenic carcinomas. Both cases went to thoracotomy, but in
      each case the requirement that malignant tissue be identified, allowed
      recognition of a foreign body in one case, and broncholith in the second,
      avoiding pneumonectomy in both cases.

PMID- 9642919
TI  - Health care for Kentucky's uninsured indigents: the perspective of providers in
      the Kentucky Physicians Care program.
AB  - The pressing issue of providing care for the uninsured indigent has been
      addressed in Kentucky by a unique private sector program that depends on
      physician donation of services. The Kentucky Physicians Care (KPC) program which
      provides health care to uninsured indigent patients in Kentucky was evaluated
      from the perspective of the participating physicians through in-depth interviews
      with 22 randomly selected physicians. The results of the interviews suggested
      that the KPC program is generally viewed by participating providers as a
      successful and personally rewarding enterprise. Suggestions for improving
      services included strategies to increase awareness of the program for both
      patients and providers. As state and federal policy continues to focus on the
      uninsured as a vulnerable population, integration of this private sector program
      into a partnership with the public sector may be a worthwhile strategy.

PMID- 9642920
TI  - ECG of the month. Plants, catsup.... Artifacts.

PMID- 9642921
TI  - Sudden sensorineural hearing loss: etiologies and treatments.
AB  - Sudden sensorineural hearing loss of 30 decibels in three contiguous frequencies,
      occurring in less than three days, is called sudden hearing loss. Although a
      number of disease processes can cause a similar hearing loss, true sudden hearing
      loss is idiopathic in nature. This review of sudden hearing loss will focus on
      the three main etiologic theories and numerous treatments studied in recent years
      in order to better enable clinicians to understand, diagnose, and treat the
      disorder.

PMID- 9642922
TI  - Radiology case of the month. Painful left hip relieved by salicylates. Osteoid
      osteoma.

PMID- 9642923
TI  - The journal 150 & 100 years ago. May 1848 and 1898.

PMID- 9642924
TI  - Comparison of pediatric hospitalization using the pediatric appropriateness
      evaluation protocol at three diverse hospitals in Louisiana.
AB  - The purpose of this study was to compare the number of inappropriate pediatric
      admissions and hospital days in three hospitals in Louisiana using Pediatric
      Appropriateness Evaluation Protocol (PAEP) criteria. The hospitals studied
      included an urban, nontertiary care, teaching hospital with 20 inpatient,
      pediatric beds (A); a private, tertiary care hospital with 30 beds (B); and a
      tertiary care, regional referral center with 133 pediatric beds (C). The study
      prospectively observed all nonintensive care pediatric admissions (> six months
      of age) between May 1 and June 30, 1993. Admissions and subsequent hospital days
      were labeled as appropriate or inappropriate based on PAEP criteria. A
      significantly shorter hospital stay (days) was demonstrated at hospital C (4.41
      +/- 1.01, p < .05) compared to A (5.98 +/- 4.95) or B (5.78 +/- 1.21). Similarly,
      hospital B had significantly more patients admitted electively (19%, p < .05)
      compared to A (4%) or C (15%). The percentage of inappropriate admissions for
      hospitals A, B, and C were 11.0, 10.0, and 2.0 (p < .05) and hospital days 18.0,
      22.0, and 12.0 (p < .05), respectively. A significant proportion of inappropriate
      hospital days came from trauma admissions in hospital A (18%, p < .05) and
      elective admissions in hospital B (36%, p < .05). Hospital A had 99% of patients
      with either Medicaid or uninsured payor status compared to 35% and 84% at
      hospital B and C, respectively. Significant differences in the rate of
      inappropriate admission or subsequent hospital days were demonstrated in the
      three hospitals studied. Finally, the rates of inappropriate hospitalization
      demonstrated in this study of Louisiana hospitals were similar to previous
      studies using the PAEP in other regions.

PMID- 9642925
TI  - A close look at family practice in Louisiana: manpower '97. Louisiana family
      practice residency program needs.
AB  - There is a shortage of family physicians in Louisiana. This manuscript reports on
      the current status of primary care in Louisiana. It compares these data with
      national averages and assesses current needs. Finally, it proposes necessary
      steps by which this shortage can be decreased. Medical schools, residency
      programs, and practicing physicians will need to be involved in the solution to
      this problem. Louisiana can have a bright future in family medicine if the
      recommendations in this paper are thoroughly addressed. With ever increasing
      costs of quality medical care, well-placed funding and emphasis on family
      practice appear to be the right direction.

PMID- 9642926
TI  - Prolymphocytic transformation of a low-grade lymphocytic neoplasia: chronic
      lymphocytic leukemia/lymphoma [corrected].
AB  - The clinical case of a patient with a low-grade lymphocytic neoplasia is
      presented. The autopsy findings revealing the transformation of the process into
      a prolymphocytic dyscrasia are also illustrated. The differential diagnosis is
      discussed.

PMID- 9642927
TI  - Utility and cost-savings of diagnostic laparoscopy in low-probability gunshot
      wounds of the abdomen.
AB  - Gunshot wounds of the abdomen are associated with a 90% or greater incidence of
      intra-abdominal injury, prompting many trauma centers to routinely explore these
      patients via laparotomy. Increasingly, diagnostic laparoscopy has been used to
      evaluated the abdomen to exclude peritoneal violation by the missile.
      Retrospective analysis of the experience at a Level I Trauma Center with 20
      isolated abdominal gunshot wound patients who did not have obvious indications
      for laparotomy such as peritonitis or shock is detailed. Outcome and cost
      analysis were compared in patients who had diagnostic laparoscopy or laparotomy.
      Patients who underwent diagnostic laparoscopy instead of laparotomy had a 42%
      reduction in operative time, a 33% reduction in hospital charges, and a reduction
      in hospital length of stay from an average of 3.5 days to less than one day. The
      only operative complication noted was in a patient who underwent laparotomy.
      Diagnostic laparoscopy may be used in select patients to exclude significant
      intra-abdominal injuries following gunshot wounds of the abdomen with reduction
      in health care costs and morbidity.

PMID- 9642928
TI  - [The review of myocardial positron emission computed tomography and positron
      imaging by gamma camera].
AB  - To measure myocardial blood flow, Nitrogen-13 ammonia. Oxygen-15 water, Rubidium
      82 and et al. are used. Each has merit and demerit. By measuring myocardial
      coronary flow reserve, the decrease of flow reserve during dipyridamole in
      patients with hypercholesterolemia or diabetes mellitus without significant
      coronary stenosis was observed. The possibility of early detection of
      atherosclerosis was showed. As to myocardial metabolism, glucose metabolism is
      measured by Fluorine-18 fluorodexyglucose (FDG), and it is considered as useful
      for the evaluation of myocardial viability. We are using FDG to evaluate insulin
      resistance during insulin clamp in patients with diabetes mellitus by measuring
      glucose utilization rate of myocardium and skeletal muscle. FFA metabolism has
      been measured by 11C-palmitate, but absolute quantification has not been
      performed. Recently the method for absolute quantification was reported, and new
      radiopharmaceutical 18F-FTHA was reported. Oxygen metabolism has been estimated
      by 11C-acetate. Myocardial viability, cardiac efficiency was evaluated by oxygen
      metabolism. As to receptor or sympathetic nerve end, cardiac insufficiency or
      cardiac transplantation was evaluated. Imaging of positron emitting
      radiopharmaceutical by gamma camera has been performed. Collimator method is
      clinically useful for cardiac imaging of viability study.

PMID- 9642930
TI  - [Frameless registration for chest SPECT and X-ray CT image by volume matching].
AB  - Image registration of functional (SPECT) and morphological (X-ray CT/MRI) images
      has been studied in order to improve the accuracy and the quality of the image
      diagnosis. This paper describes a new registration method for chest SPECT and X
      ray CT images. Presented method is a frameless and automatic registration method
      which calculates a transformation matrix between two coordinate systems of image
      data by an optimization method. This registration method uses similar physical
      characteristics of X-ray CT and transmission CT image. The three-dimensional
      overlap of the body region is used for image matching. Precision evaluation and
      visual image evaluation were conducted. The result of the precision evaluation
      with a phantom and clinical data suggested the clinically acceptable robustness
      in registration procedure. Visual evaluation of registered images confirmed the
      usefulness of this method in clinical applications.

PMID- 9642929
TI  - [Clinical utility of pulmonary 99mTc-Tetrofosmin uptake measurement by the
      exercise myocardial scintigraphy in patients with ischemic heart disease].
AB  - Increased pulmonary 201TlCl (Tl) uptake during exercise has been used as a marker
      of multivessel critical stenosis. We studied whether pulmonary 99mTc-Tetrofosmin
      (TF) uptake measurement during exercise is useful as an additional indicator for
      the detection of coronary artery disease. Pulmonary to myocardial uptake ratio
      (P/M) measured by TF scintigraphy during exercise were compared with findings of
      coronary angiography in eighty one patients with ischemic heart disease and also
      P/M measured with Tl in twenty one cases. TF P/M level in the patients with
      triple vessel disease was higher than that in the patients with no coronary
      stenosis, single vessel disease and double vessel disease. However, there was no
      significant correlation between TF P/M and the severity of coronary artery
      stenosis. Inverse correlation was observed between TF P/M and left ventricular
      ejection fraction (LVEF) (r = 0.29, p < 0.01). TF P/M in the patients less than
      50% of LVEF was significantly higher than that in the patients over 50% of LVEF
      (p = 0.05). TF P/M was well correlated with Tl P/M (r = 0.86). In conclusion,
      quantitative TF P/M during exercise was thought to be useful indicator for the
      evaluation of coronary artery disease.

PMID- 9642931
TI  - [Regional cerebral blood flow measurements by a noninvasive microsphere method
      using 123I-IMP: comparison with the modified fractional uptake method and the
      continuous arterial blood sampling method].
AB  - A noninvasive microsphere method using N-isopropyl-p-[123I]iodoamphetamine (123I
      IMP), developed by Yonekura et al., was performed in 10 patients with
      neurological diseases to quantify regional cerebral blood flow (rCBF). Regional
      CBF values by this method were compared with rCBF values simultaneously estimated
      from both the modified fractional uptake (FU) method using cardiac output
      developed by Miyazaki et al. and the conventional method with continuous arterial
      blood sampling. In comparison, we designated the factor which converted raw SPECT
      voxel counts to rCBF values as a CBF factor. A highly significant correlation (r
      = 0.962, p < 0.001) was obtained in the CBF factors between the present method
      and the continuous arterial blood sampling method. The CBF factors by the present
      method were only 2.7% higher on the average than those by the continuous arterial
      blood sampling method. There were significant correlation (r = 0.811 and r =
      0.798, p < 0.001) in the CBF factor between modified FU method (threshold for
      estimating total brain SPECT counts; 10% and 30% respectively) and the continuous
      arterial blood sampling method. However, the CBF factors of the modified FU
      method showed 31.4% and 62.3% higher on the average (threshold; 10% and 30%
      respectively) than those by the continuous arterial blood sampling method. In
      conclusion, this newly developed method for rCBF measurements was considered to
      be useful for routine clinical studies without any blood sampling.

PMID- 9642932
TI  - [Usefulness of ECG-gated 99mTc-MIBI myocardial SPECT in the follow-up study of
      patients with acute myocardial infarction].
AB  - To clarify the background of the scintigraphic improvement in non-gated
      myocardial perfusion imaging for patients with acute myocardial infarction, we
      performed serial ECG-gated 99mTc-MIBI myocardial SPECT in 17 patients with acute
      myocardial infarction (AMI) receiving successful reperfusion therapy. ECG-gated
      myocardial SPECT and left ventriculography were performed at 1 week (acute phase)
      and 1 month (subacute phase) after the onset of AMI. Regional %uptake (regional
      count x 100/maximal count) was determined for each of 8 myocardial segments of
      the Bull's eye map. We analyzed the data in 53 AMI segments out of total 136
      myocardial segments, on the non-gated (NG), end-diastolic (ED), and end-systolic
      (ES) images. In addition, the delta %uptake (%uptake in subacute phase--%uptake
      in acute phase) was also determined as an index representing the improvement of
      myocardial tracer uptake on each image. In 17 segments (group A) with wall motion
      recovery assessed by serial left ventriculography, the %uptake on the NG image
      was significantly improved (61.6 +/- 10.0 to 75.7 +/- 10.1, p < 0.0001). However,
      in 36 segments (group B) without wall motion recovery, the change of %uptake on
      the NG image was small. There was no significant change in the %uptake on the ED
      image in groups A and B. On the contrary, the %uptake on the ES image showed a
      significant increase in group A (58.4 +/- 11.8 to 68.9 +/- 11.8, p < 0.001), but
      did not in group B. Thus, this change on the ES image reflects the wall motion
      recovery. Furthermore, in group A, there was a significant correlation between
      the delta %uptake on the NG image and those on the ES image (p < 0.02), but was
      not between those on the NG and the ED images. Thus, the change in the %uptake on
      the NG image was more related to those on the ES image which is more affected by
      the change in regional wall motion than those on the ED image which reflects
      improved myocardial perfusion. These results suggest that ECG-gated myocardial
      99mTc-MIBI SPECT is more useful to assess the serial change in myocardial
      perfusion and contraction than the conventional non-gated SPECT in the follow-up
      study of patients with AMI.

PMID- 9642933
TI  - [Prognostic value of myocardial 123I-BMIPP imaging in patients with congestive
      heart failure without coronary artery disease].
AB  - We performed 123I-BMIPP (BMIPP) imaging in order to clarify the characteristics
      of fatty acid metabolism and its effect on prognosis in patients with congestive
      heart failure (CHF) without coronary artery disease. We studied 15 normal
      subjects and 42 patients with CHF (idiopathic dilated cardiomyopathy; 24,
      hypertensive heart disease; 12, valvular heart disease; 6). We obtained cardiac
      imaging with BMIPP and 201Tl at rest on separate days before discharge. Using
      whole body imaging, the ratio of cardiac uptake of the isotope to total injected
      dose was calculated (%Uptake). We calculated the cardiac uptake ratio of BMIPP
      (%Uptake of BMIPP divided by %Uptake of 201Tl), percent washout of BMIPP from the
      heart over 3 hours and unhomogeneity of myocardial distribution of BMIPP
      (coefficient of variation of BMIPP, CV) as scintigraphic parameters. Cardiac
      events were defined as cardiac death or deterioration of CHF which requiring
      readmission. Uptake ratio (CHF: 0.91 +/- 0.17, normal; 1.10 +/- 0.09, p = 0.0000)
      and CV (CHF; 20 +/- 5, normal; 16 +/- 5, p = 0.0385) were different significantly
      between CHF and normal subjects. During the follow-up period of 27.2 +/- 14.4
      months (4.5-53.5 months) cardiac events developed in 15 patients (cardiac death;
      8, deterioration of CHF; 7). In univariate analysis, %uptake of 201Tl, uptake
      ratio, % FS, serum norepinephrine level and serum renin activity were different
      significantly between event and event-free groups. Cox proportional hazard
      analysis showed that the uptake ratio (p = 0.0000) and age (p = 0.018) were
      independent predictors of cardiac events. In patients with uptake ratio less than
      0.88, relative risks of cardiac events was 23.7 times greater than in patients
      with uptake ratio more than 0.89. These data suggested that in patients with CHF
      fatty acid metabolism was deteriorated and cardiac uptake of BMIPP was a strong
      and independent predictor of long-term prognosis in patients with heart failure.

PMID- 9642934
TI  - [Some considerations on the avoidance of excess body burden in case of high dose
      131I treatment: with special reference to the urination frequency].
AB  - In case of the treatment of metastatic thyroid cancer with radioiodine (131I),
      3.7 GBq (100 mCi) or more is often repeatedly administered to the patient.
      Therefore, we must be aware of avoiding unnecessary exposure to the radioiodine
      except for the lesions to be treated. The administered radioiodine is excreted
      mainly through urinary system, resulting in an accumulation of the urine in the
      bladder for a certain period, which is highly concentrated with it. Based on this
      fact, we set one case having a particular pattern of the whole body retention
      curve. Then, two different modes of urination were considered; mode A indicates
      every 2 hour-urination x 6 times followed by every 6 hour-urination x 2 times,
      and mode B indicates every 6 hour-urination x 4 times. Focusing on the different
      amounts of urine in the bladder upon the different modes of urination, the
      radiation exposures from the urine to the neighboring organs, such as bladder
      wall, uterus, ovary and testis, and also to the whole body were calculated. As
      the results, it was found that the urination mode B would cause radiation
      exposure from the urine in the bladder twice as much as the urination mode A to
      the neighboring organs as well as to the whole body. This study will supply
      arguments for the necessity of frequent urination in the cases receiving
      radioiodine treatment for metastatic thyroid cancer.

PMID- 9642935
TI  - [Epidemiological study on penicillin-resistant Streptococcus pneumoniae].
AB  - We studied the differences among clinical isolates of Penicillin-resistant
      Streptococcus pneumoniae by polymerase chain reaction (PCR) of pbp2b gene,
      followed by serotyping and pulsed field gel electrophoresis (PFGE) analysis.
      Clinical isolates were recovered from sputum samples from patients with
      respiratory infection in Tottori University Hospital between June 1986 and May
      1996. By PCR, altered pbp2b genes of the resistant isolates were detected in
      76.5%. The percentages of the isolates that had altered pbp2b genes increased
      concomitantly with the minimum inhibitory concentration (MIC). By serotyping the
      percentage of 19F, 23F, 6B and 14 was 54.5%, 18.2%, 9.1% and 9.1% respectively.
      The frequency of isolates resistant to penicillin increased rapidly from 1991 in
      this hospital and most isolates belonged to serotype 19F. The resistant isolates
      in this hospital and 4 clinical resistant isolates of S. pneumoniae 19F in a
      second hospital were studied by PFGE. 14 of 18 resistant 19F isolates in this
      hospital and all 19F isolates from the second hospital presented an identical
      pattern. The remaining 4 samples were similar though not completely identical.
      These results indicate that the penicillin resistant 19F isolates have a common
      clonal origin and have spread rapidly from 1991 in this hospital.

PMID- 9642937
TI  - [The role of heat shock protein 60 (HSP60) of Helicobacter pylori in adhesion of
      H. pylori to human gastric epithelial cell].
AB  - Adhesion of Helicobacter pylori to both human gastric carcinoma cell lines
      (MKN45, MKN28 and KATO III) and prepared primary human gastric epithelial cells
      were analyzed with flow-cytometry. All strains adhered to human gastric carcinoma
      cells. Especially, these strains strongly adhered to MKN45 cells. Adhesion of H.
      pylori strains to prepared primary human gastric epithelial cells was also
      observed. However, the adherence rates of H. pylori to these cells were different
      among the cells used. These results suggested that the host factor might be
      important for adhesion of the bacteria to human gasgric cells. In addition, H20
      monoclonal antibody directed to H. pylori HSP60 inhibited the adhesion of H.
      pylori to both cells. These results indicate that H. pylori HSP60 might be
      associated with the adhesion of the bacteria to human gastric epithelial cells.

PMID- 9642936
TI  - [Immunization with one dose of inactivated influenza vaccine].
AB  - In the winter of 1996, a total of 71 working adults from 20 to 60 (m = 37.3)
      years of age were immunized with one or two doses of inactivated influenza
      vaccine formulated in Japan. The reciprocal geometric mean hemagglutination
      inhibition antibody titers [mean HI] and the percentage with a hemagglutination
      inhibition titer of > or = x 128 [percent > or = x 128], against A/
      Yamagata/32/89 (H1N1), A/Uhan/359/95 (H3N2), and B/Mie/1/93 were significantly
      elevated by either doses. The pre-/post-vaccination mean HI of H1N1 were
      61.5/668.4 with one dose, and 85.7/637.3 with two doses. The percent > x 128 were
      36.5/96.2 with one dose, and 47.4/94.7 with two doses. No significant differences
      were apparent between one and two doses. Similarly, nonsignificant differences
      were observed for the other two antigens contained in the vaccine. We observed
      the sufficient immune response to only one dose of inactivated influenza vaccine,
      which emphasizes the merit of one dose method of influenza immunization.

PMID- 9642938
TI  - [Febrile episodes in elderly inpatients--a one year survey to determine the
      causes of fever in hospital].
AB  - To determine the cause of nosocomial infections, all febrile episodes of
      hospitalized elderly patients aged 65 and older at a hospital in Fukuoka City
      were categorized between April 15 1994 and April 14 1995. A febrile episode was a
      temperature above 37.5 degrees C after 7 consecutive days of normal body
      temperature (below 37.5 degrees C). Various clinical tests including blood
      examination, urinalysis, chest radiography and bacterial culture were done on the
      first and 7th day of the fever. A total of 1105 episodes in 443 patients (male
      136, female 307) fulfilled this criteria for fever. The fevers were mainly due to
      respiratory tract (381 cases, 34.5%) and urinary tract infections (263 cases,
      23.8%). There were 135 infections (12.2%) of other kinds and 297 cases (26.9%)
      that were classified as unknown. Approximately 70% of the febrile episodes were
      caused nosocomial infections, suggesting increased risk of infection in the
      hospitalized elderly and the importance of early detection of febrile changes in
      elderly inpatients.

PMID- 9642939
TI  - [Shigella dysenteriae strains possessing a new serovar (204/96) isolated from
      imported diarrheal cases in Japan].
AB  - Five Shigella strains isolated from stool cultures of imported diarrheal cases in
      Japan, did not react to any antisera of the established Shigella serovars. These
      strains had the typical biochemical characteristics of Shigella dysenteriae, and
      were biochemically identical. All strains were positive in the Sereny test and
      other tests for invasivness; these indicate that they can cause shigellosis in
      humans. The results of antigenic analysis revealed that they did not belong to
      any of the recognized or provisional serovars, and were serologically
      indistinguishable. They had the same drug-resistance pattern (CP.TC.SM.ABPC.ST)
      and plasmid-profile. Strain 96-204 is designated as the test strain for this new
      serovar.

PMID- 9642940
TI  - Evaluation of two commercial diagnostic kits for Mycobacterium tuberculosis
      completely based on bacterial DNA and rRNA amplification for direct detection of
      tubercle bacilli in sputum specimens.
AB  - The Roche Amplicor Mycobacterium Tuberculosis Kit (Amplicor PCR) and Gen-Probe
      Amplified Mycobacterium Tuberculosis Direct Test (MTD) were compared for
      efficiency in the direct detection of tubercle bacilli in sputum specimens. In
      total, 72 sputum specimens obtained from patients with active tuberculosis were
      examined with the Amplicor PCR and MTD kits. Of the 72 test specimens, 45 and 41
      samples were positive by the Amplicor PCR and MTD methods, respectively. These
      values were larger than those obtained by the culture method (Septi-Chek) and
      acid-fast bacilli-smear test, yielding 37 and 20 positive results, respectively,
      and the sensitivities were as follows: smear, 39.2%; culture, 72.5%; Amplicor
      PCR, 88.2%; MTD, 80.4%. Amplicor PCR was similarly or somewhat more sensitive in
      direct detection of M. tuberculosis in sputum samples from patients with
      clinically active tuberculosis than was MTD.

PMID- 9642941
TI  - [Prevention of Lyme borreliosis infection after tick bites].
AB  - Lyme borreliosis is one of the zoonotic and vectorial diseases in the world.
      Female of Taiga tick, Ixodes persulcatus play an important role being the main
      vector of the agents, Borrelia burgdorferi sensu lato, of the disease in the Far
      East including Japan. The number of patients who contacted Lyme borreliosis have
      been estimated to be around 100 cases in all of Japan. We also detected the
      spirochetes from the skin tissues of 27 cases involving erythema and 3 cases
      without erythema after tick bites in Hokkaido. We noticed that in those cases
      when the victims removed ticks by themselves using their fingers within several
      days later, almost all of them developed erythema. On the other hand, an infected
      tick from 8 cases which were removed by surgical procedure, the spirochetes were
      not transmitted in these cases (No. 31-38). Therefore, we supposed that the
      transmission of agents takes place by regurgitation of the spirochestes from the
      midgut diverticula due to the pressure by fingers (calling Syringe phenomenon).
      Then, the authors recommended that fine tweezers has a firm grip around the mouth
      part of infested tick and pull out within 24 hours and/or trials to surgical
      operation for tick removal on passing over 24 hours after infestation.

PMID- 9642942
TI  - [Respiratory failure in polymyositis and dermatomyositis: differential diagnosis
      between pulmonary infection and interstitial pneumonitis].
AB  - Pulmonary diseases are important cause of morbidity and mortality in patients
      with PM/DM. Thirteen (27%) out of 49 PM/DM patients in the study had developed
      respiratory failure. Respiratory failure resulted form interstitial pneumonitis
      (i.p.) in 6, pulmonary infection in 2 and both in 5 patients with PM/DM.
      Respiratory failure was fatal in PM/DM patients with pulmonary diseases and
      eleven of the 13 patients expired. More importantly, 2 PM/DM patients with
      respiratory failure had responded to chemotherapy, if it was due to pulmonary
      infection. Accordingly, it is almost important to distinguish i.p. and infection
      for the cause of respiratory failure. However, plain chest X-ray as well as
      standard laboratory tests failed to differentiate i.p. and pulmonary infection.
      On the other hand, high resolution CT of the lungs, serum endotoxin and serum
      beta-D-glucan were found to be useful for the differentiation of these conditions
      associated with respiratory failure in PM/DM patients. And additionally low serum
      level of IgG and lymphopenia at the onset of respiratory failure may suggest that
      the patients may have pulmonary infection rather than i.p.

PMID- 9642943
TI  - [Experimental studies of polymorphonuclear leukocyte on mandibular bone infection
      model in rabbit].
AB  - Polymorphonuclear leukocytes (PMN) play important roles in the prevention of
      infection at an early stage. We studied the function of these leukocytes using
      rabbit models of mandibular bone infection to evaluate the conditions which could
      not be reproduced in human beings Streptococcus milleri NCTC7331 and Bacteroides
      fragillis NCTC9343 were inoculated into the mandibular bone of rabbits using the
      Satoh-Heimdahl method, to produce supposed multiple infection models. Rabbits
      inoculated with these bacteria were used as a test group, and animals with
      surgically induced inflammation were used as a control group. We compared the
      number of leukocytes, the function of PMN, and histopathologic findings. 1) The
      number of leukocytes increased after treatment, reached a perk on day 3,
      gradually diminished later, but remained slightly higher than the baseline level
      on day 7, with persistence of inflammation in both groups. 2) Adhesiveness,
      ability to migrate and NBT reduction, were accelerated in both groups. 3) These
      functions of PMN accelerated more in the test group because the bacteria
      inoculated induced stronger inflammatory reactions and activated a series of
      infection defense mechanisms in the hosts. 4) Histopathologic examination after
      treatment showed invasion of inflammatory cells, predominantly leukocytes, in
      both groups, but heavier and more extensive infiltration in the group treated
      with the bacteria. All measurements were higher in the test group than the
      control group. These results showed that in the test group, causative or
      accompanied microorganisms activated the host's infection defense mechanisms and
      accelerated the functioning of PMN at an acute stage of infection.

PMID- 9642944
TI  - [Difference of host response in identical toxin-produced Staphylococcus aureus
      injected mice].
AB  - Biological activities of two strains of Staphylococcus aureus (S. aureus), KU-1
      06-37 and KU-1-12-44, which produce enterotoxin type C, TSST-1 and alpha-toxin
      were examined using Std:ddY strain mice. These two strains were found to be
      different in lethality, ratio of weight loss, induction of leukopenia, adhesion
      to surrounding organs and clearance period of bacterial cells from the liver,
      kidney and spleen within 24 hrs after intraperitoneal injection in the mice. All
      of them were weak or fast in KU-1-12-44 injected mice. Serum amyloid A on all the
      KU-1-06-37 and KU-1-12-44 injected mice rose within 5 hr to 18 hr. However, this
      concentration of KU-1-12-44 injected mice was about 40% lower compared with that
      of KU-1-06-37 injected mice at 21 hr. On the other hand, ability of bacterial
      adhesion to established cell lines, Vero and HeLa cells, was tested in vitro.
      Percentage adhesion of KU-1-06-37 was high to both cells, but that of KU-1-12-44
      was high to Vero cells and was low to HeLa cells. Adhesion of KU-1-06-37 to HeLa
      cells that were treated with lipoteichoic acid was about 40% inhibition compared
      with untreated cells, although that of KU-1-12-44 to them was inhibited only 9%.
      As the results, identical toxin-produced KU-1-06-37 and KU-1-12-44 showed
      different biological activities in vivo and in vitro. Not only toxin production
      but also adhesion to cells or organs in mice may contribute to S. aureus
      virulence to the host.

PMID- 9642945
TI  - [Two cases of hematological malignancies diagnosed before death as aspergillosis
      with skin lesion].
AB  - We report two cases of aspergillosis with skin lesions. The first involved a 63
      year-old female with acute lymphocytic leukemia. In 1992, she received
      chemotherapy for acute leukemia. Subsequently, she noted swelling of her leg, a
      skin biopsy was performed and Aspergillus flavus was isolated. The second patient
      was a 71-year-old male with myelodysplastic syndrome. In 1996, he developed a
      massive inguinal abscess from which Aspergillus fumigatus was isolated. The
      prognosis of aspergillosis was poorer in the case with skin swelling than in the
      one with a massive abscess.

PMID- 9642946
TI  - [A case of Listeria monocytogenes sepsis in an elderly who survived].
AB  - A 81-year-old man who complained of fever and disturbance of consciousness was
      admitted to our hospital. Listeria monocytogenes type 1/2aA was cultured from
      only the blood. He was treated with gamma-globrine and sensitive antibiotics
      (PAPM/BP, EM) immediately after admission, and recovered in spite of multiple
      organ failure due to septic shock. He was not an immunocompromised host and did
      not have complication of meningitis, but had rhabdomyolysis and liver
      dysfunction.

PMID- 9642947
TI  - [A case of Kartagener's syndrome associated with pulmonary tuberculosis,
      pneumothorax and pulmonary aspergilloma].
AB  - A case of Kartagener's syndrome associated with multiple pulmonary complication
      was presented. A 19-year-old man was admitted to our hospital because of
      pulmonary tuberculosis in May 1972. He had been diagnosed as Kartagener's
      syndrome because of the presence of chronic parasinusitis, bronchiectasis and
      complete situs inversus. His chest radiographs in Dec 1972 revealed left
      pneumothorax. Chest radiographs in Aug 1975 appeared aspergilloma in the right
      middle lung field. He was administrated intravenous and oral anti-fungal agent
      and transbronchial installation of Amphotericin-B because of hemoptysis. Chest
      radiographs in July 1980 resolved the aspergilloma and his symptom were also
      resolved. In 1996, he had no pulmonary symptoms and respiratory failure. We
      consider that the Kartagener's syndrome was good prognosis with adequate
      pulmonary therapy.

PMID- 9642948
TI  - [Human parvovirus B19-induced aplastic crisis in a case with spherocytosis].
AB  - A 43-year-old female with spherocytosis was admitted to the hospital because of
      fever, headache, and rapidly progressive anemia. On admission, she had severe
      anemia (Hb 3.9 g/dl) with marked decrease in reticulocytes (0.3%). Some premature
      leukocytes, such as promyerocyte, were observed in the peripheral blood. Bone
      marrow smear revealed normocellular marrow with normal presence of erythroid
      cells. Anti-human parvovirus B19 IgM and IgG antibody was positive in the serum
      on admission. The DNA of the virus was also detected in the peripheral blood by
      PCR assay. Thus, this case was diagnosed as acute aplastic crisis caused by human
      parvovirus B19 infection. Blood transfusion was performed on day 1 and day 2. The
      symptoms gradually disappeared and increase in reticulocyte (11.5%) was observed
      on day 5. Premature leukocytes in the peripheral blood disappeared on day 2. She
      recovered from anemia and was discharged on day 7.

PMID- 9642949
TI  - [Pulmonary tuberculosis with diabetes mellitus, presenting multiple nodular
      shadows].
AB  - An asymptomatic 52-year-old male, who was diagnosed as poorly controlled diabetes
      mellitus (DM), was referred to our hospital because of abnormal shadows on chest
      X-rays. Physical examinations and laboratory data showed no abnormal findings
      except increased values of blood sugar and HbA1c (12.1%). Chest X-ray and CT scan
      revealed multiple nodular shadows in both lung fields. The specimens from
      transbronchial biopsy showed epithelioid granuloma, and Mycobacterium
      tuberculosis was confirmed with bronchial wash fluid. The patient was then
      treated with antimycobacterial drugs and sulfonylurea along with diet therapy.
      The multiple nodular shadows gradually disappeared. It seemed that impaired host
      defense mechanisms caused by poorly controlled DM is responsible for the
      bronchogenic dissemination of M. tuberculosis, resulting in the extension into
      the multiple nodular shadows. Thus, a good control of DM is important for the
      prevention of an onset and excerbation of tuberculosis in patients with DM.

PMID- 9642950
TI  - [Surgical treatment of reflux esophagitis and peptic stricture of esophagus].
AB  - Reflux-esophagitis is wide-spread and frequently diagnosed disease, which is
      found in persons of young and adult age. The main kind of treatment is
      conservative one, however sometimes reflux-esophagitis is accompanied by
      complications, dangerous for life, which require surgical treatment. Experience
      of surgical treatment of 720 patients is available. Fundoplication procedure in
      RCS modification combined with SPV is main and optimal operation. This operation
      is possible in more than 2/3 cases of surgical treatment of reflux-esophagitis
      and peptic stricture of the esophagus. If it is found to be impossible to carry
      out organ saving procedure in severe reflux-esophagitis and irreversible peptic
      stricture of the esophagus the operation of choice should be extirpation of the
      esophagus and gastroplasty with gastric tube or large bowel and simultaneous
      creation of anastomosis in the neck. This was carried out in 38 patients with
      favourable outcomes.

PMID- 9642951
TI  - [Spiral computer tomography in diagnosis of hepatic diseases].
AB  - Spiral computer tomography (SCT) is a new method of computer tomography by which,
      in contrast to conventional CT, the information about absorptional capacity of
      tissues is obtained without omission of images which makes it possible to build
      MPR and 3D of a very high quality. 205 patients with diseases of
      hepatopancreatoduodenal area were examined, in 189 patients the diagnosis being
      verified. Optimal technique of intravenous bolus contrasting in SCT was
      developed. Using various time interval between the start of the scanning and the
      beginning of infusion of contrast media, it is possible to obtain primary image
      of the arteries (arterial phase of contrasting, time of delay 18-25 sec.), the
      picture of veins and the image of saturation of hepatic parenchyma--(venous
      return phase, time of delay 60-80 sec.), to reveal characteristics of contrasting
      of the liver masses during delay (8-15 min) phase. The largest quantity of masses
      are revealed in arterial phase of contrasting. Specific features of contrasting
      in hemangiomas and malignant tumors of the liver has been revealed. Hemangiomas
      absorb contrast medium already at the early phase as hypercontrasted lacunas in
      an outlying areas, at a late phase they are hyperdenced in relation to hepatic
      parenchyma. Primary and metastatic tumors of the liver accumulate contrast medium
      in an early phase along the whole area and quickly lose contrast medium during
      parenchymal phase. The method of contrast intensification enables evaluation of
      interrelation between tumor and vessels, to determine passage of hepatic arteries
      and branches of portal and hepatic veins, to visualise choledochal duct, to
      determine the distance between hepatic and tumor surface, and to produce these
      data as a view of multiplanar and three-dimensional image (reconstruction). The
      effectiveness of obtained reconstructions in planning of the extent of surgical
      intervention is demonstrated.

PMID- 9642952
TI  - [Diagnosis and treatment of liver echinococcosis complicated by cysto-biliary
      fistula].
AB  - 890 patients with echinococcosis of the liver were operated during 1976-1992.
      Complicated forms of the disease were li detected in 222 (24.9%) patients, among
      them 141 (15.8%) patients with cysto-biliary fistulas. Ultrasonography
      examination and endoscopic retrograde cholangiography were regarded as the most
      informative methods of preoperative diagnosis of cysto-biliary fistulas. Three
      stage management was worked out. The usage of laser, plasmatic scalpel and
      ultrasound of low frequency substantially contributed to improvement of the
      results of treatment of these patients.

PMID- 9642953
TI  - [Pre- and postoperative correction of hyposiderosis in surgical treatment of
      portal hypertension].
AB  - In order to study iron metabolism disorders in patients with portal hypertension
      syndrome, to determine clinical significance of hyposiderosis and to work out
      effective method of its correction, 94 patients with cirrhosis of the liver
      complicated by portal hypertension were examined. As a result of determination of
      these disorders of iron metabolism methods for treatment of hypochromal anemia
      and hyposiderosis have been worked out. Hemotransfusions, administration of iron
      containing preparation Ferrum-lec and combination of these methods were used for
      treatment. It was established that administration of large doses of iron
      containing preparation Ferrum-lec substantially contributed to improvement of
      iron metabolism in patients with cirrhosis of the liver and extrahepatic portal
      hypertension, to reduction of postoperative complications rate and to upgrading
      the results of surgical treatment.

PMID- 9642954
TI  - [Ultrasound diagnosis of acute cholecystitis].
AB  - The results of ultrasonographic examination of the gall-bladder in its acute
      inflammation in 1070 patients are presented. Parallels between the anatomic
      changes and ultrasound visual picture of the inflamed wall of the gall-bladder
      were drawn. The analysis of the results of the examination revealed the most
      typical symptoms of acute cholecystitis and permitted to differentiate it from
      similar ultrasonographic symptoms in other diseases of the gall-bladder. From all
      patients who underwent surgical treatment or diagnostic laparoscopy, the
      diagnosis was confirmed in 97%. The possibilities of the method in a series of
      patients after the operation and patients with concomitant diseases are limited,
      in such cases the punction or drainage of the gall-bladder under the ultrasound
      scan control for diagnostics and treatment is advisable.

PMID- 9642955
TI  - [Roentgenological examination of stomach after pancreatoduodenectomy].
AB  - High frequency of complications after pancreatoduodenal resections dictates the
      necessity to study causes of their origin. This paper provides the results of
      roentgenologic examinations in early and late postoperative periods in 24
      patients who underwent classic pancreatoduodenal resection by Whipple and in 23
      patients after pylorus saving pancreatoduodenal resection--operation by Traverzo
      Longmire. Conventional method of roentgenologic examination of the operated
      stomach was used. In early postoperative period disturbances of motor-evacuatory
      function of upper parts of gastrointestinal tract were revealed in 50% of
      patients in any modification of pancreatoduodenal resection. In most cases
      slowering down of the evacuation up to complete gastrostasis was observed. But in
      long-term follow-up functional results after pancreatoduodenal resection
      according to x-ray examination data were much better after operation by Traverzo
      Longmire (75% patients) than after classic version by Whipple (37% patients).
      Thus, the results of roentgenologic examination showed that pylorus saving
      version of pancreatoduodenal resection provides optimal conditions for normal
      activities of the saved organ.

PMID- 9642956
TI  - [Lumbar sympathectomy].
AB  - Indications for application of lumbar sympathectomy (LS) in chronic arterial
      insufficiency of the lower extermities are analyzed. The results of the use of
      lumbar chemical desympathisation under computer tomography (CT) control in 10
      patients are represented. Prevalences of chemical desympathisation and LS were
      revealed which allow us to recommend it for clinical practice.

PMID- 9642957
TI  - [Postoperative treatment of retroperitoneal fat suppuration in patients with
      gastrointestinal injuries].
AB  - Early diagnosis of retroperitoneal festering is possible if methodologically
      strictly carrying out of succession of radiation methods (US, computed
      tomography, roentgenological examination) is applied and used in complex.
      Extraperitoneal approach to phlegmon of retroperitoneal cellular tissue provides
      good visualization and is less traumatic. Infusional and enteral therapy in
      postoperative period promote effective elimination of volemic disturbances,
      stabilization of hemodynamic indices, and provides stable curative effect.

PMID- 9642958
TI  - [Early reconstructive-restorative operations in vast traumatic injuries of shin
      complicated by purulent infection].
AB  - The experience in treatment of 278 patients with extensive traumatic injuries of
      the shin complicated by purulent infection is represented. Multistage treatment
      typical for such category of patients in which reconstructive-restorative stage
      is performed late after elimination of inflammatory process is not optimal. Owing
      to the complex of treatment measures based on the principles of active surgical
      treatment of festering wounds primary operations were a success in 24.6% of
      patients. In 75.4% of patients early dermoplastic and osteoplastic operations
      were carried out to 1 month after primary surgical treatment. Good and favourable
      results obtained in 98.6% of patients demonstrate effectiveness of the above
      policy of treatment.

PMID- 9642959
TI  - [Intravascular laser irradiation of blood in treatment of traumatic abdominal
      organs injuries].
AB  - The application of intravascular laser irradiation of the blood (ILIB) in
      combined postoperative intensive care in 28 patients with traumatic injuries of
      parenchymal organs and severe intraabdominal bleeding (more than 20% CBV)
      contributed to substantial improvement of the results of treatment and reduction
      of complications rate. ILIB boosts functional activity of leucocytes, normalizes
      the system of hemostasis and antioxidant defence.

PMID- 9642960
TI  - [Diagnosis and therapeutic punctures of abdominal organs under ultrasound
      control].
AB  - Data on 32 diagnostic punctures of the liver, pancreas and spleen under
      ultrasonographic US control are available. False diagnosis was registered in 1
      case. 16 curative procedures under US control were carried out in patients with
      hepatic abscesses (7), suppurative pseudocysts of the pancreas (4), abscesses of
      the abdominal cavity (5); in 4 patients external drainage extrahepatic bile ducts
      was carried out. This method, being not much traumatic, produces good results in
      definite group of surgical patients.

PMID- 9642961
TI  - [Wound healing process differences in type I and type II diabetes mellitus].
AB  - In 88 patients with purulent wounds in diabetes mellitus the course of wound
      healing was studied depending on the type of the disease. Clinical and
      morphological distinctions of the wound process in type 1 and type 2 diabetes
      mellitus were revealed.

PMID- 9642962
TI  - [Liposuction].
AB  - Hemostasis was studied in 38 women aged from 24 to 40 years before the
      liposuction procedure and 2-3 days after it. The results obtained evidence for
      substantial postoperative hypercoagulation changes with simultaneous inhibition
      of antithrombine and fibrinolytic activities. Signs of thrombophilic inclination
      as a result of hematocrite lowering due to hypervolemic hemodilution. It is
      necessary to control hemostasis before the liposuction procedure. The advantage
      of hypervolemic hemodilution in prophylaxics of thromboembolic complications is
      shown. The category of persons of risk has been determined.

PMID- 9642963
TI  - [Psychological, moral-ethic and deontologic aspects of relaparotomy].
AB  - Analysis of the results of relaparotomy in 208 patients is presented.
      Psychological, moral, ethic and deontologic aspects of repeated laparotomy have
      been studied. In indications for relaparotomy the choice of the surgeon is
      advisable to make as a collective decision, on individual basis, after careful
      analysis of the causes of postoperative complications and with regard for the
      wish of the surgeon who performed the first operation. In 137 patients of 208
      relaparotomy was carried out by the surgeon by whom the first operation was
      performed, with the assistance of more experienced surgeons. Lethality made up
      35% (48 patients died after the operation). 60 patients were reoperated by the
      other surgeons with the assistance of the surgeon who had carried out primary
      operation. In 11 cases relaporotomy was carried out without participation of the
      surgeon who had performed the initial laparotomy. 24 (33.8%) patients died after
      relaparotomy performed by the other surgeons. "Radical" relaparotomies were
      carried out in 141 patients, in 94 (66.7%) of them being performed by the surgeon
      who had done the initial operation and in 47 (33.3%)--by the other surgeons. 25
      (17.7%) patients died after "radical" relaparotomies and after "palliative"--47
      (70.1%) patients. Total lethality after relaparotomy made up 34.6%.

PMID- 9642964
TI  - [Saphenoextractor].
AB  - New saphenoextractor, including flexible volute-shaped conductor and string
      stylet, is proposed and successfully fried. The instrument contains mobile
      removable handle with collect as well as a set of olives with collect grip. The
      conductor is leaded through the vein's lumen, than the string is introduced into
      its lumen and the conductor is withdrawn. The handle is fixed at one end of the
      string and the olive--at the other one after which the vein is extracted.
      Clinical experience of surgical treatment of varicose veins disease in 105
      patients has shown the advantages of the proposed device over other well-known
      veinextractors.

PMID- 9642965
TI  - [Blood flow measurement in palmar arterial arch of hand and digital arteries].
AB  - As a result of examination of 20 healthy people by the method of ultrasound
      dopplerography normal values of blood flow in palmar arterial arch of the hand
      and digital arteries were established. In the course of examination by this
      method of 50 patients with various diseases of arteries of upper extremities
      hemodynamically responsible areas for lowering of blood flow were revealed. These
      were axileary artery, bifurcation of the brachial artery, both arteries of the
      forearm and arterial arch of the hand. Blood flow intensity in the arteries of
      the hand and fingers refleds the condition of collateral blood flow in the upper
      extremity.

PMID- 9642966
TI  - [Management of linea Spigellii hernia in outpatient clinics].

PMID- 9642967
TI  - [Cyst of pancreatic head with rupture and profuse bleeding into the lumen of
      duodenum].

PMID- 9642968
TI  - [Vascular isolation of liver in its vast resections].

PMID- 9642969
TI  - [Ernst Bergman (1836-1907)].

PMID- 9642970
TI  - Autoimmune causes of recurrent pregnancy loss.
AB  - Recurrent pregnancy loss (RPL) is the loss of 3 or more spontaneous and
      consecutive pregnancies. There are many causes, such as genetic, anatomic,
      hormonal, medical and immunologic causes. Two theories, the alloimmune and the
      autoimmune theories, explain the immunologic cause. The Antiphospholipid Antibody
      (APA) Syndrome is considered as the autoimmune cause of RPL. It involves two
      antibodies, Lupus anticoagulant (LAC) and the anti-cardiolipin antibody (ACA).
      The rate of LAC is 7% and of ACA is 15%, among pregnant women. These two
      antibodies are believed to cause thrombosis in the maternal circulation, leading
      to the events that lead to the fetal losses. Women with these antibodies, along
      with other factors, are believed to be at high risk for RPL. The diagnostic
      criteria for the APA syndrome include elevated LAC or ACA serum levels and
      clinical findings of thrombosis, thrombocytopenia and RPL. Presently, the medical
      treatment of the APA syndrome includes heparin, low-dose aspirin, and
      immunoglobulins. There must also be an active attempt to search for other causes
      of RPL among patients with APA syndrome, such as anatomic, endocrinologic,
      anatomic and medical problems. Management of RPL should also include extensive
      counseling for the patient and her family.

PMID- 9642971
TI  - Prevalence of antibody to Toxoplasma gondii in Hyogo Prefecture, Japan:
      comparison at a 10-year interval.
AB  - We have previously surveyed antibody to Toxoplasma gondii among Japanese
      populations. In this report, we studied the current situation of antibody
      prevalence and compared it with the situation approximately 10 years before. A
      total of 1,800 human serum samples were collected at the Central Laboratory of
      Kobe University Hospital from June through September, 1995, and were examined for
      Toxoplasma antibody using enzyme-linked immunosorbent assay. The overall
      prevalence was found to be 16.4% with similar seropositivities in males (16.8%)
      and females (15.9%). Prevalence of antibody increased with age, reaching 41.0% in
      males and 59.0% in females at 80 years or more. Comparison with data obtained at
      the same hospital in 1981 to 1982 indicated that seropositivities at 30-39 years
      significantly decreased in both males and females. A positivity currently
      obtained at a certain age group was similar to a positivity previously obtained
      at the corresponding age group (10 years younger), indicating that the previous
      age prevalence curve shifted to the current position. A serological survey among
      stray cats collected in Hyogo Prefecture in 1990-1991 indicated that 44 (19.0%)
      of 231 cats were positive for Toxoplasma antibody as determined by the latex
      agglutination test. These results suggested less transmission of Toxoplasma to
      humans in Hyogo Prefecture at least for the last 10 years comparing with the
      situation in the past, although the transmission cycle among cats was still
      active in nature.

PMID- 9642972
TI  - Periodic limb movement disorder in neuroleptic-induced akathisia.
AB  - We recorded all-night polysomnograms of four schizophrenic patients with
      neuroleptic-induced akathisia (NIA) before and during treatment with clonazepam.
      Also, four non-akathitic schizophrenic patients were recorded all-night
      polysomnograms as control subjects. Daily treatment with 1.5 to 3 mg clonazepam
      improved subjective complaints of all the 4 patients with NIA. Three of 4
      patients with NIA exhibited periodic limb movements (PLM) on bilateral legs, but
      none of 4 control subjects showed PLM. Total number of PLM and PLM per hour
      decreased during clonazepam treatment. Moreover, mean inter-movement intervals of
      PLM of 3 patients were prolonged on bilateral legs. NIA might change its feature
      as PLM during night sleep.

PMID- 9642973
TI  - Non-selective cation conductance in a Xenopus renal epithelial line.
AB  - The currents activated in single cells of an epithelial cell line from renal
      tubules of Xenopus laevis, were studied, using a whole-cell voltage-clamp
      technique. After the patched membrane was broken for the whole-cell recording,
      the currents developed transiently, reaching a peak in 20 min, in cells held
      under voltage-clamp. The currents did not show voltage- and time-dependent gating
      behavior at membrane potentials between -100 and +100 mV. The current-voltage
      relationships showed strong outward rectification. The ratio of the absolute
      amplitude of the current at a potential of +60 mV to that at -60 mV was 24.4 +/-
      3.6. The reversal potentials of the currents under various ionic conditions imply
      that the membrane conductance was preferentially permeable to cations but that it
      had a finite permeability to anions. The cation conductance was non-selective for
      monovalent cations and also permeable to Ca2+, with a permeability sequence
      (relative to Na+); Na+: K+: Cs+: Li+: Ca2+ = 1.0: 1.3: 1.4: 1.0: 0.7. These
      results suggest that in A6 cells, the non-selective cation conductance activated
      after the rupture of the patch membrane, may play an important role in epithelial
      transport of fluid and electrolyte and that its Ca2+ permeability could be
      involved in some physiological signal transduction.

PMID- 9642974
TI  - Airway lesions and superoxide dismutase (SOD) distribution in bronchopulmonary
      dysplasia (BPD).
AB  - We examined 71 cases of bronchopulmonary dysplasia (BPD) at autopsy and divided
      them into five groups on the basis of the patients' survival time, studying on
      the histological changes in the airways for the purpose of clarifying the
      pathogenesis of BPD from hyaline membrane disease (HMD). Furthermore, bronchiolar
      occlusion was classified into four types: secretion, obliterative bronchiolitis,
      intraluminal plug, and hyperplasia of bronchiolar components. The same occlusive
      findings as in bronchioli and hyaline membrane were observed from respiratory
      bronchioles to alveolar ducts. However, there was no obvious correlation between
      airway lesions and accompanying alveolar lesions excepts three cases of
      obliterative bronchiolitis. Furthermore, immunohistochemical studies with anti
      human SOD antibodies were performed. Mn-SOD was positive for alveolar macrophages
      in longer surviving infants without significant correlation with histological
      variation, whereas slightly positive or negative in infants who died within 1
      week; CuZn-SOD was rarely positive in any cases. These results is highly
      correlated to the pathogenesis of BPD and to its pathological advancement with
      its clinical course.

PMID- 9642975
TI  - The legal/ethical mix.

PMID- 9642976
TI  - Risk management and the Dental Practice Act.

PMID- 9642977
TI  - Get rid of the dental garbage.

PMID- 9642978
TI  - Survival of the profession.

PMID- 9642979
TI  - Valuable information.

PMID- 9642980
TI  - Certified dental assistants. Dentistry's newest professional category.

PMID- 9642981
TI  - Dentistry and malpractice. Looking back on 13 years.

PMID- 9642982
TI  - DSSNY course bolsters dentists' defenses.
AB  - The DSSNY risk management course was born of crisis. Now in its fifth version,
      the course is credited with increasing competition among malpractice carriers and
      lowering premium prices.

PMID- 9642983
TI  - Risk management and the claims process.
AB  - This article explores certain risk management techniques and the role these
      techniques play in the investigation and evaluation of claims. The claims
      experience of one carrier, Medical Liability Mutual Insurance Co., is provided. A
      general overview of the elements involved in a claims investigation is provided.

PMID- 9642984
TI  - For the record. Understanding patient recordkeeping.

PMID- 9642985
TI  - [Extracellular matrix and hepatobiliary surgery].

PMID- 9642986
TI  - A clinical study of elderly patients with acute cholecystitis.
AB  - In recent years, an increase in average life expectancy has led to a rapid rise
      in the number of elderly patients undergoing surgery for acute cholecystitis. We
      studied the clinical characteristics of elderly patients (aged 75 years of more)
      undergoing surgery for acute cholecystitis, as compared with those of non-elderly
      patients (aged less than 75 years) undergoing similar procedures. Twenty-four of
      the patients were elderly, and 44 were non-elderly. RESULTS: Echography and
      abdominal computed tomography (CT) revealed no characteristic findings specific
      to elderly patients, but a smaller proportion of elderly patients showed a three
      layered structure of the gallbladder wall. The leukocyte count on admission was
      significantly lower in elderly patients than in non-elderly patients. As for
      therapy, a significantly higher proportion of elderly patients underwent
      percutaneous transhepatic gallbladder drainage (PTGBD) + cholecystectomy +
      choledochotomy/choledocholithotomy, as compared with non-elderly patients. In
      contrast, cholecystectomy alone was performed more frequently in non-elderly
      patients than in elderly patients. The main postoperative complications were
      psychic symptoms and respiratory tract infections. The postoperative hospital
      stay was significantly longer for elderly patients, in part because they
      requested to remain in the hospital until they were able to perform activities of
      daily living.

PMID- 9642987
TI  - A case of early gastric carcinoma with acute gastric mucosal lesions presenting
      difficulty in differentiating advanced gastric carcinoma.
AB  - An 87-year-old man diagnosed as having advanced gastric carcinoma was admitted to
      our hospital. In a barium X-ray examination of the stomach taken at another
      hospital, filling defects were obseved in the greater and lesser curvatures of
      the antrum, while the entire pyloric region was rigid and stenotic. The
      gastroscopic findings showed pronounced curvature and stenosis of the pylorus and
      the pyloric mucosa was edematous and sclerotic. Histopathological examination of
      a biopsy specimen from the pylorus indicated a group V. The gastroscopic findings
      subsequent to admission displayed pronounced improvement with only sporadic
      shallow ulceration and erosion. The histopathological findings of the excised
      specimen showed that several depressed lesions in the antrum were active ulcers
      or their scars and the depressed lesions extending from the antrum to the pyloric
      ring were early gastric carcinoma. The findings of filling defects of the antrum
      and stenosis with ridigity of the pyloric region in the radiographic examination,
      and pronounced curvature and stenosis of the pylorus and sclerosis with edema of
      the pyloric mucosa in the gastroscopic examination were very similar to typical
      findings of advanced gastric carcinoma with pyloric stenosis. In addition,
      histopathological examination of a biopsy specimen from the pylorus indicating a
      group V made differentiation from advanced gastric carcinoma extremely difficult.

PMID- 9642988
TI  - [Pathologic features of acute allograft rejection in ABO-incompatible renal
      transplantation].
AB  - BACKGROUND: In order to examine the difference in histological findings during
      acute rejection between ABO-incompatible renal transplantation and compatible, we
      studied biopsy specimens from renal allografts histopathologically. METHODS:
      Twenty one ABO-incompatible cases (ICBG) and fifteen compatible cases (CBG) who
      were transplanted at Tokyo Women's Medical College and considered to have acute
      rejection clinically were selected. Lightmicroscopic findings classified Banff
      schema, deposition of globulins and complements, expression of HLA class II
      antigen (DR) and adhesion molecules (ICAM-1, VCAM-1), subset of infiltrating
      cells, blood type antigen and specific antigen for endothelium (Thrombomoduline:
      TM, Factor VIII) were compared between CBG and ICBG on biopsy specimens. RESULTS:
      Tubulitis was observed in 71.4% of ICBG and all cases of CBG. Severe interstitial
      infiltration of CD8 positive cells and polymorphonuclear leucocyte (PMN)
      glomerular infiltration was showed in 52%, 85.7% of ICBG and 100%, 0% of CBG. The
      incidence of fibrinogen deposits was 47.6% in ICBG and 26.7% in CBG. Tubular
      expression of DR, ICAM-1 and VCAM-1 were positive in 25%, 40%, 45% of ICBG and
      91.7%, 100%, 100% of CBG. Monoclonal antibody for TM was demonstrated more
      strongly positive in CBG (73.3%) than in ICBG (28.6%). These findings had
      significant differences in ICBG from CBG. CONCLUSIONS: Acute rejection of ABO
      compatible renal transplantation was characterized by tubulitis accompanied by
      high expression of DR, ICAM-1 and VCAM-1, which subsequently injure tubulo
      interstitium. On the other hand, ABO-incompatible acute rejection showed
      endothelial injury characterized by fibrinogen deposition and severe PMN
      infiltration in glomeruli (glomerulitis).

PMID- 9642989
TI  - [Regional lymph node metastasis in renal pelvic or ureteral cancer].
AB  - BACKGROUND: The objective of this study is to evaluate the frequency of regional
      lymph node metastasis, clinical outcomes and histopathological findings of renal
      pelvic or ureteral cancer with regional lymph node metastasis. PATIENTS AND
      METHODS: One hundred and sixty three patients with renal pelvic or ureteral
      cancer were treated in our hospital between 1961 and 1995. Eighty nine in 155
      patients underwent lymph node dissection. Frequency of regional lymph node
      metastasis, clinical outcomes and histopathological findings of these 89 patients
      were investigated. Patient survival rates were determined by actuarial
      calculation using Kaplan-Meier method with log-rank test. RESULTS: The status of
      lymph node involvement was pN0 in 61 (68.5%), pN1 in 5 (5.6%), pN2 in 15(16.9%)
      and pN3 in 8 patients (9.0%). The 5-year survival rate was 78.8%, 12.5%, 20.0%
      and 0% for pN0 pN(+), pN1, pN2 and pN3 respectively. In 28 patients with regional
      lymph node metastasis, patients with distant metastasis were all dead within 1.2
      years and the 3- or 5-yer survival rates of patients without distant metastasis
      were 31.4% and 15.7%. The difference between two groups were obvious (p < 0.01).
      The 3-year survival rate was 100%, 66.7%, 33.3% and 0% for pT1, pT2, pT3 and pT4
      patients with M0 and pN(+) respectively. CONCLUSION: Our data suggested that
      conventional treatments were not effective for almost patients with regional
      lymph node metastasis. However in the patients with low grade, under pT3 and M0,
      pN1-2, the possibility of long time survival was shown.

PMID- 9642990
TI  - [Immunohistochemical analysis of expression of angiogenic factors and tumor
      angiogenesis in superficial bladder cancer].
AB  - PURPOSE: We evaluated expression of angiogenic factors, tumor vessel density and
      recurrence in superficial bladder cancer by immunohistochemistry. METHODS: Fourty
      tumor specimens from bladder preserving operation and 11 normal epithelia were
      stained for factor VIII-related antigen, vascular endothelial growth factor
      (VEGF), basic fibroblast growth factor (bFGF) and acidic fibroblast growth factor
      (aFGF). Maximum vessel density (MVD) was counted in a 200x field in the highest
      vascularized area stained for factor VIII. Superimposing a 4 x 4 square ocular
      grid on the boundary between epithelium and interstitium, average vessel density
      (AVD) and vascular surface density (VSD) were calculated by dividing the vessel
      number in the grid and the intersection number of vessel walls on the lattice
      lines by the area of interstitium calculated from the number of the gird cross
      points, respectively. RESULTS: Positive rates of VEGF, bFGF and aFGF by
      immunohistochemistry were 50%, 23% and 43% in the superficial bladder cancer,
      respectively. The positive rate of VEGF staining was higher in G2-3 tumors than
      in G1 tumors. All normal epithelia, except one which was positive for aFGF, was
      negative for those three factors. T1 tumors had a higher MVD than that of Ta. AVD
      and VSD of the tumor were higher than those of normal epithelium, but negative
      correlation between the number of positive angiogenic factors and the vessel
      density was revealed. The recurrence group had a lower vessel density and a
      higher ratio of VSD/AVD than those of the non-recurrence group. CONCLUSION: These
      findings suggest that the expression of VEGF, bFGF and aFGF was not reflected by
      the tumor angiogenesis, the angiogenesis is required topically at the invasive
      front of the superficial bladder cancer, and the tumor which had fewer and
      broader tumor vessels has a high tendency to recur.

PMID- 9642991
TI  - [A study of the differences between the sexes in epidemiology of urolithiasis].
AB  - PURPOSE: Uroithiasis seems to be the dominant disease for male. In the recent
      Japanese epidemiological report, the sexual ratio was reported 2.3:1. This sexual
      ratio is almost stable from 1960. We studied epidemiologically based on age and
      stone components the differences between the sexes. PATIENTS AND METHOD: From
      1977 to 1996 the upper urinary tract stones which spontaneous excretion or
      surgical removal in our hospital were the subjects of study, Stone analysis was
      carried out infrared spectrometer. The statistical analyses were performed by the
      chi-square test and Mann-Whitney's U test. Significance was declared for a
      probability value of less than 0.05. RESULTS: In the epidemiology of our treated
      patients sexual ratio was 1.83:1. We studied sexual ration in age and stone
      components. The sexual ratio of the patients, 60 years and over was decreased
      compared with that of the patients under 60 years of age. We found the tendency
      that the sexual ratio was decreased at 60 years old and over. In the female
      urolithiasis patients less than 60 years old the frequency of calcium oxalate
      contained stone patients was predominantly smaller than male. In the female
      urolithiasis patients of 60 years and over the stone component ratio was similar
      to male urolithiasis patients. CONCLUSION: In point of frequency sexual ratio was
      decreased at 60 years old and over. In the female patients less than 60 years old
      the frequency of calcium oxalate contained stone was predominantly small. This
      low frequency of calcium oxalate contained stone in the female less than 60 years
      old seemed to be a factor of the sex differences of frequency.

PMID- 9642992
TI  - [Tumor volume and percent of gland involvement with tumor as predictors of
      pathological stage in prostate cancer].
AB  - BACKGROUND: It is well recognized that tumor volume correlates with pathological
      stage, histological grade and progression in prostate cancer. We analyzed the
      tumor volume and the percent of gland involvement with tumor (%TV/PV) to
      determine if either or both of these morphometric factors would be good
      predictors of pathological stage. METHODS: The pathological reviews were
      retrospectively performed on the basis of the 22 step sectioned prostate
      specimens removed by radical retropublic prostatectomy for clinical T1c-T2-T3
      prostate cancer. The percent of gland involvement with tumor was calculated using
      the following formula [100 x (tumor volume cc/prostate volume cc)]. When the
      patients had organ confined disease (OCD) or specimen confined disease (SCD) they
      were defined as surgically cured patients, whereas the patients with positive
      surgical margin, seminal vesicle involvement or positive lymph node were defined
      as not surgically cured patients. RESULTS: The likelihood of OCD was 25% in
      patients with clinical T1c-T2 disease. No patients with clinical T3 had OCD.
      Patients with SCD was not observed. The mean tumor volume was 1.3 cc in the
      surgically cured patients and 6.2 cc in the not surgically cured patients. The
      tumor volume correlated with pathological stage (r = 0.607, p = 0.0054). The mean
      %TV/PV was 3.23% in the surgically cured patients and 18.2% in the not surgically
      cured patients. The %TV/PV also correlated with pathological stage (r = 0.543, p
      = 0.0129). Both the tumor volume and the %TV/PV in surgically cured patients were
      less than those in the not surgically cured patients. A correlation between tumor
      grade and both the tumor volume and the %TV/PV were not observed. CONCLUSION: The
      tumor volume and the %TV/PV correlated well with the final pathological stage.
      Multiple regression analysis showed that the tumor volume was the best predictor
      of pthological stage.

PMID- 9642993
TI  - [Hyperbaric oxygen therapy for radiation-induced hemorrhagic cystitis].
AB  - BACKGROUND: Radiation therapy has widely been used for cancers in the pelvis.
      Radiation cystitis, one of the late complications, presents often as hemorrhagic
      cystitis, which is refractory to the conventional therapy and may threaten the
      patient's life. We used hyperbaric oxygen therapy on patients with radiation
      cystitis to test its potential benifit. METHODS: Ten patients aged from 46 to 81
      years with a mean of 62 years underwent one or more courses of hyperbaric oxygen
      therapy according to their symptoms, consisting of 20 sessions (3 to 5 sessions a
      week) at the Department of Hyperbaric Medicine, the University of the Ryukyus
      Hospital in the 9-year period from 1985 to 1994. They included 8 patients having
      a history of cervical cancer, one with external genital cancer and one with
      vaginal cancer. During the 75 min hyperbaric oxygen therapy patients received
      100% oxygen at 2 absolute atmosphere pressure in the Multiplace Hyperbaric
      Chamber. RESULTS: Hematuria subsided and subjective symptoms including urinary
      frequency improved in seven patients. Cystoscopic findings including mucosal
      edema, redness, and capillary dilation were partially improved. The procedure
      subjectively and objectively palliated the 10 patients in a favorable manner.
      CONCLUSIONS: To date we have not armed any active procedure to control radiation
      induced refractory hemorrhagic cystitis in terms of efficacy, invasiveness, and
      adverse effects. Therefore, in consideration of our clinical results, hyperbaric
      oxygen therapy appears to be useful for radiation cystitis.

PMID- 9642994
TI  - [Renal malignant lymphoma: report of a patient surviving 17 months without
      recurrence and review of 43 Japanese cases].
AB  - A case of renal malignant lymphoma is reported. A 74-year-old man was admitted to
      our hospital on September 8, 1995, complainning of right flank pain, abdominal
      mass, and anorexia for two months. Physical examination revealed an enlarged
      right axillary lymph node and abdominal mass of child's head size. Computerized
      tomography showed a tumor (11 x 7 cm) encompassing the right kidney parenchym,
      and enlarged paraaprtoc lymph nodes with invasion of the left iliac creat.
      Transcutaneous echo-guided needle biopsy revealed that the tumor was non
      Hodgkin's malignant lymphoma, diffuse large cell type, positive for B cell
      marker. The patient was treated with full dose of CHOP regimen. However,
      adriamycin was replaced with pirarubicin and the dose of the other drugs were
      reduced for the subsequent 4 courses because of severe leukocytopenia,
      thrombocytopenia, hepatotoxicity, and alopecia after the first course of the
      treatment. The patient showed complete remission and discharged on March 12,
      1996. He, after 17 months, has no signs of recurrence. We reviewed 43 Japanese
      cases previously reported as renal malignant lymphoma. It is increasing in Japan
      especially in elderly. The 2-year survival is 26.6%.

PMID- 9642995
TI  - [A case of metastasis to the seminal vesicle of renal cell carcinoma].
AB  - A case of metastasis to the seminal vesicle of renal cell carcinoma is reported.
      A 60-year-old man was referred to our department for evaluation of intermittent
      hematospermia and asymptomatic macrohematuria for about 2 years. He had a left
      radical nephrectomy for localized renal cell carcinoma 5 years ago. Panendscopy
      showed a little bleeding of posterior urethra, but there were no abnormal images
      of upper urinary tracts. Two years later he had asymptomatic macrohematuria again
      and panendscopy showed swelling and bleeding of verumontanum. Transurethral
      resection of verumontanum revealed clear cell carcinoma histopathologically and
      CT revealed seminal vesicle or prostate tumor, then total cystectomy was
      performed. Pathological examination indicated metastasis to siminal vesicle of
      renal cell ccarcinoma. There has been no report of metastasis to seminal vesicle
      of renal cell carcinoma in literature. This is the first case in the world.

PMID- 9642996
TI  - [Primary adrenal schwannoma].
AB  - We report a rare case of retroperitoneal schwannoma arising from left adrenal
      gland. A 45-year-old man with upper abdominal discomfort was found to have a
      tumor in the left adrenal gland by abdominal ultrasonographic scan. The
      laboratory findings were all normal but angiogram indicated slightly
      hypervascular adrenal tumor. Eventually, he was underwent left adrenalectomy. The
      removed mass was measured 6.5 x 5.7 x 5.0 cm and weighed 75.5 g. Pathological
      study revealed benign schwannoma arising from the adrenal gland, consisting
      mainly of the Antoni A type. A review of the literature on adrenal schwannoma is
      included.

PMID- 9642997
TI  - [Retropharyngeal node metastasis in cancer of the oropharynx and hypopharynx:
      analysis of retropharyngeal node dissection regarding preoperative radiographic
      diagnosis].
AB  - In our department, all patients with advanced carcinoma of the oropharynx and
      hypopharynx are treated by retropharyngeal (RP) node dissection in addition to
      primary resection and standard neck dissection. Records of 42 patients (11
      oropharynx, 29 hypopharynx and 2 retromandibula) who received RP node dissection
      from 1992 to 1996 in our department were examined for metastasis to RP nodes and
      for preoperative radiographic diagnosis (MRI or CT). The criteria for
      radiographic involvement of RP nodes are as follows: a diameter greater than 10mm
      on axial images or central necrosis within the nodal substance. Of the 42
      patients, 6 (14.3%) had pathologically positive RP nodes and of those 6 patients,
      5 were able to be diagnosed preoperatively by either CT scan or MRI. Results of
      radiographic diagnosis (MRI or CT) were as follows: by CT scan the sensitivity,
      specificity and accuracy were all 100% and by MRI the sensitivity, specificity
      and accuracy were 83.3%, 100% and 97.0% respectively. It is our conclusion that
      preoperative radiographic diagnosis (MRI or CT) is very useful and effective for
      diagnosis of metastasis to RP nodes.

PMID- 9642998
TI  - [Clarion 16 cochlear implant (System introduction and use experience in Japan].
AB  - The Clarion cochlear implant was developed in the USA and received FDA approval
      in August 1996. It consists of an implantable cochlear stimulator (ICS), speech
      processor with headpiece, and in addition, a clinician's programming system and
      portable cochlear implant tester. One of the features of the device is its
      stimulation-coding process for which two methods of continuous interleaved
      sampling (CIS) and compressed analogue (CA) are applicable. Regardless of which
      is used, stimulation can be provided over 8 channels. The device was used in 2
      cases. Both patients were operated on in October 1996, and 16 electrodes in 8
      pairs were mounted in the cochlea. Mapping, performed 3 weeks after the
      operation, showed good speech perception in both patients with only a cochlear
      implant in the "open-set" status. CIS was used as the stimulation-coding method.
      CA has yet to be applied.

PMID- 9642999
TI  - [Result of treatment of squamous cell carcinoma of the tongue and floor of the
      mouth].
AB  - A statistical analysis was performed on 40 patients with squamous cell carcinoma
      of the tongue and mouth floor, which could be followed for 6 months or more after
      initial treatment in the Department of Otorhinolaryngology, School of Medicine,
      Keio University during the 14 years from 1983 to 1996. The 5-year survival rate
      determined by the Kaplan-Meier method for each stage was 100% for Stage I, 77.8%
      for Stage II, 60.0% for Stage III and 44.4% for Stage IV. Thirteen suffered a
      relapse after initial treatment and patients with relapses among them have all
      survived after the subsequent salvage surgery. In contrast, in nine patients with
      cervical relapse, however, the 5-year survival rate was 11.1% with an unfavorable
      prognosis. This confirmed that suppressing cervical relapses is important for
      treating tongue and floor mouth cancers. The treatment strategy in our department
      is characteristic of positive enforcement of prophylactic neck dissection in the
      surgery and introduction of neoadjuvant chemotherapy (NAC) in the chemotherapy.
      Prophylactic neck dissection was performed in the 17 patients and no relapse was
      observed on the side of prophylactic neck dissection. NAC was performed on 26
      patients in consideration of suppressed minute metastases and preserved function
      and 24 determinable cases were statistically analyzed. Among patients who had
      received NAC, the oral function was successfully preserved without surgical
      intervention in six patients both patients who showed complete response (CR) and
      four out of 14 patients who had a partial response (PR) following NAC. This may
      indicate that the oral function could be preserved in those patients who
      exhibited CR following NAC, but that preservation could be difficult in patients
      who exhibited PR. In addition, concerning the accumulated 5-year survival rate in
      relation to the effect of NAC, responders (CR + PR) accounted for 90.9% and non
      responders (no change + progressive disease following NAC) for 15.0% with a very
      good outcome noted in the responder group. These figures suggest that responders
      may have a significantly good prognosis in the multivariant analysis including
      additional background factors before treatment as well. Accordingly, the present
      therapeutic measures for non-responders must be reexamined and performed more
      carefully and accurately as compared with those for responders.

PMID- 9643000
TI  - [An immunohistochemical study of RB tumor suppressor gene protein and bcl-2 gene
      protein in carcinomas of the thyroid gland].
AB  - The expression of RB and bcl-2 proteins was investigated in 135 thyroid
      carcinomas (130 papillary carcinomas and five follicular carcinomas) by the
      immunohistochemical technique with RB and bcl-2 monoclonal antibodies. The
      results were as follows: 1) RB protein nuclear staining was shown in 117 of the
      135 thyroid carcinomas (87%). Bcl-2 protein staining was shown in 82 of the
      carcinomas (61%). 2) There was a higher incidence of recurrence in RB-negative
      cases than in RB-positive cases (chi 2 test p = 0.001). But there is no
      significant relationship between the incidence of recurrence and the results of
      bcl-2 staining (chi 2 test p = 0.287). 3) The expression of RB protein was
      related to age and clinical N and M categories. Bcl-2 protein expression was
      related to clinical T categories. 4) The 10-year overall survival rate for RB
      positive patients was higher than that for negative patients (long-rank test p <
      0.0001). But the survival rate was not associated with bcl-2 expression (log-rank
      test p = 0.3). Our results suggest that assessment of RB protein expression by
      the immunohistochemical technique may be useful to determine the possibility of
      recurrence and to predict the outcome of thyroid carcinomas. We think that
      assessment of RB protein expression by the immunohistochemical technique can be
      applied as a more sensitive prognostic factor.

PMID- 9643001
TI  - [Statistical analysis of oropharyngeal squamous cell carcinoma--multivariate
      analysis of prognostic factors and evaluation of therapeutic modalities].
AB  - Ninety-one cases of oropharyngeal squamous cell carcinoma initially treated at
      Keio University Hospital between July 1981 and June 1996 were reviewed
      retrospectively. There were 83 males and 8 females, aged from 29 to 83 years old,
      with an average age of 62.7. The primary lesion was located in the lateral wall
      in 52 patients (57.1%), the superior wall in 23 (25.3%), the anterior wall in 14
      (15.4%) and the posterior wall in 2 (2.2%). Double cancer was detected in 21
      patients (23.1%). The patients were divided into two groups according to the
      initial main treatment of the primary lesion without regard to chemotherapy: 72
      patients (79.1%) who received curative radiotherapy with or without salvage
      surgery, and 14 patients (15.4%) who underwent curative surgery with or without
      preoperative and/or postoperative radiation. The remaining 5 patients were
      treated by chemotherapy alone. Prior to the above treatments 50 patients (54.9%)
      received neoadjuvant chemotherapy (NAC). Survival distributions were estimated by
      the Kaplan-Meier method as univariate analysis, and compared by the generalized
      Wilcoxon test. The overall five-year cumulative survival rate was 55.6%. The five
      year survival rates according to stage (UICC classification, 1987) were as
      follows: stage I (11 cases), 70.7%; stage II (12 cases), 63. 6%; stage III (30
      cases), 52.3%; and stage IV (38 cases), 52.5%. Significant clinicopathological
      variables that influenced survival were: (1) T stage (p = 0.0075); (2) age (p =
      0.0274); and (3) location of primary lesion (p = 0.0400). The results of
      multivariate analysis by Cox's proportional hazards model identified T stage as a
      significant independent prognostic factor. Evaluation of the therapeutic
      modalities led to the following conclusions. (1) Differences in the initial
      treatments of the primary lesion were not reflected in the outcome. (2) Salvage
      surgery for residual or recurrent tumor contributed to improving the survival.
      The superior wall type, in particular, seemed to be a good indication for salvage
      surgery. (3) Although the limitations of radiotherapy are not defined clearly, we
      have to determine the indications for radical resection of tumors resistant to
      radiotherapy with reconstruction. (4) The response rate of NAC reached 85.4%, but
      there were no significant differences in survival between the group that
      underwent NAC and the other group in any other subset analyses. (5) Among the
      patients who underwent NAC, the responder (CR + PR) group showed a better five
      year survival rate (61.3%) than the non-responder (NC + PD) group (42.9%), but
      the difference was not significant.

PMID- 9643002
TI  - [The mechanism of positive scintigraphy with 99mTc-pertechnetate in
      adenolymphomas of the parotid grand].
AB  - In order to clarify the mechanism of positive scintigraphy with Tc pertechnetate
      in adenolymphomas of the parotid gland, 10 cases of adenolymphoma were studied
      morphologically and from a functional view point. Salivary tissue obtained from
      normal parotid glands were also investigated for comparison with the tumor. In
      morphological studies, rapid tissue fixation by microwave irradiation produced
      very good results for examining mitochondria by high resolution light microscopy.
      A number of mitochondria were found both in the epithelial cells of adenolymphoma
      and in the striated duct cells of the parotid gland. In functional studies, the
      one-step method of enzymatic histochemistry was used for detecting Na-K ATPase.
      Na-K ATPase was found on the baso-lateral side of the epithelial cells of
      adenolymphoma and the striated duct cells of the parotid gland, and this activity
      of Na-K ATPase may enhance the accumulation of Tc pertechnetate in these cells.
      These observations may provide evidence for the bi-cellular theory which
      indicates that adenolymphoma originated from immature intercalated duct reserve
      cells.

PMID- 9643004
TI  - [The latest design method of the dwellings for the elderly persons].

PMID- 9643003
TI  - [Calretinin immunoreactivity in olfactory bulb and mucosa in mice].
AB  - The vertebrate olfactory system is capable of recognizing and discriminating
      thousands of different odorant molecules. In vitro biochemical studies have shown
      that some odorants elicit an increase in the intercellular second messenger
      cyclic AMP, whereas other odorants cause an increase in the second messenger
      inositol triphosphate (IP3). If IP3 plays an important role in the signal
      transduction, calcium-binding protein will be needed. We investigated the
      expression of calretinin, which belongs to the E-F hand family, in the neonatal
      and adult olfactory mucosa and olfactory bulb. Mice were sacrificed on postnatal
      day 1 (P1), day 3 (P3), day 10 (P10) and 12 weeks as adults. The olfactory mucosa
      of the nasal septum and the olfactory bulb were stained with anti-calretinin
      antibody at a 1:1000 dilution for 48 hours. The results were as follows. 1)
      Olfactory mucosa: In the P1 mouse, the olfactory nerves running in the submucosal
      layer and olfactory cells in the epithelium were positive. In the epithelium,
      immunopositive spots were seen exclusively in the upper half of the epithelium.
      In the P3, P10 and adult mice, these spots were seen throughout the olfactory
      cell layer. However, the basal cell layer and supporting cells were negative. 2)
      Olfactory bulb: In all stages, the olfactory nerve layer and the glomerular layer
      were strongly stained. In the external plexiform layer, many cells were positive.
      Their shape was bipolar and the size of the cell body was thought to be about 20
      microns. They were thought to be tufted cells. However, there is a possibility
      that these cells are short axon cells in the external plexiform layer. In the
      granule layer, some granule cells were positive. In the P1 mouse, the
      immunopositive spots were exclusively seen in the upper half of the epithelium.
      In contrast, in the P3 mouse, these spots were seen throughout the olfactory cell
      layer. Judging from our results, it is suspected that the important change in
      neurogenesis of olfactory cells occurred between P1 and P3. In the olfactory
      bulb, from P1 to adult mice, calretinin was positive in the olfactory nerve
      layer, the glomerulus and periglomerular cells. In contrast, mitral cells were
      negative. Most reports state that calcium binding protein appears in
      periglomerular cells. However, in the external plexiform layer, many cells were
      positive. As their shape was bipolar and the cell body was a little larger than
      the periglomerular cells, these cells were thought to be tufted cells.

PMID- 9643005
TI  - [Biological function of AGE].

PMID- 9643006
TI  - [Molecular mechanism of neuronal cell death in Alzheimer's disease].

PMID- 9643007
TI  - [Effect of inflammatory cytokines and oxidized low density lipoprotein on
      vascular endothelial growth factor expression in macrophage].
AB  - Vascular endothelial growth factor (VEGF), also known as vascular permeability
      factor, is a specific mitogen for vascular endothelial cells and causes
      neovascularization and capillary hyperpermeability. We previously found large
      amounts of VEGF peptide in areas with many macrophage-derived foam cells adjacent
      to the lipid core of human atherosclerotic plaques and in basal regions of plaque
      consisting predominantly of smooth muscle cells. In the present study, we
      examined the role of inflammatory cytokines and oxidative modified low density
      lipoprotein (OX-LDL) in the expression of macrophage VEGF. Interleukin 1 beta and
      tumor necrosis factor alpha upregulated the expression of VEGF mRNA in a
      macrophage cell line (RAW264). In addition, OX-LDL also upregulated the
      expression of VEGF mRNA in these cells in a time-dependent and a dose-dependent
      dependent manner, and there was an increase in the levels of VEGF protein in the
      conditioned medium. These results suggest that VEGF expression may be upregulated
      in atherosclerotic lesions and that VEGF may play a role in the development of
      atherosclerosis.

PMID- 9643008
TI  - [Characterization of amyloid beta protein species in the plasma, cerebrospinal
      fluid and brains of patients with Alzheimer's disease].
AB  - Extracellular deposition of amyloid beta protein (A beta) as senile plaques and
      cerebral amyloid angiopathy (CAA) is one of the essential pathological
      characteristics of Alzheimer's disease (AD). Several A beta species with
      different carboxyl termini, including A beta 42 (43) and A beta 40 ending at
      residue 42 (43) and 40, respectively, have been identified in CAA and in senile
      plaque cores. Because A beta 42 (43), the major component of diffuse plaque which
      is the earliest pathological change in AD brains, forms insoluble amyloid fibrils
      more rapidly than does A beta 40, it has been hypothesized that A beta 42 (43)
      plays a role in amyloid seeding and A beta 40, in the elongation of amyloid
      fibrils on a seed of A beta 42 (43). We used enzyme-linked immunosorbent assay
      (ELISA) with site-specific monoclonal antibodies to differentiate A beta 42 (43)
      from A beta 40. First, we measured the amounts of different A beta species in
      plasma from patients with sporadic probable AD, age-matched patients with
      neurologic diseases but without dementia, and age-matched normal controls.
      Concentrations of A beta 1-40 and A beta 1-42 (43) in plasma did not differ
      significantly among the three groups. Second, CSF levels of A beta species (CSF-A
      beta) with different carboxy termini, i.e., A beta X-40 and A beta X-42 (43) as
      well as A beta 1-40 and A beta 1-42 (43), were measured in patients with AD and
      in age-matched controls without dementia using ELISA. Levels of both CSF-A beta X
      42 (43) and A beta 1-42 (43) were significantly lower in the patients with AD
      that in the controls, but neither the levels of CSF-A beta X-40 nor those of CSF
      A beta 1-40 differed between the two groups, which suggest that increased
      adsorption of A beta 42 (43) to A beta deposition in AD brains, decreased
      secretion of A beta 42 (43) in CSF, or increased clearance of A beta 42 (43) from
      CSF might explain the low levels of A beta 42 (43) in the CSF of patients with
      AD. Third, we measured the concentrations of various A beta species post-mortem
      in the cerebral cortex of patients with PS-1 mutations and beta amyloid precursor
      protein (APP) 717 mutation linked to familial AD or Down syndrome. The results
      indicate that one effect of PS-1 mutations, APP717 mutation and Down syndrome is
      to cause dramatic and accelerated accumulation of A beta 42 (43) in the brain as
      compared with sporadic AD. In particular, the increases in A beta 1-42 (43)
      showed a crude inverse correlation with the age of onset in each subtype of AD.
      Thus, quantitative studies differentiating A beta 42 (43) from A beta 40 have
      established the fundamental importance of A beta 42 (43) in AD.

PMID- 9643009
TI  - [DNA analysis for prevention and treatment of osteoporosis].

PMID- 9643010
TI  - [A new approach to pneumonia in the elderly: pathophysiology and therapy].
AB  - Pneumonia is a major cause of death in the elderly. Swallowing disorders caused
      by cerebrovascular diseases can cause frequent aspiration during sleep, which can
      result in pneumonia. Patients with aspiration pneumonia may have abnormalities in
      systems involving dopamine-substance P in the central and peripheral nervous
      system. Activation of these systems may benefit elderly people with swallowing
      disorders.

PMID- 9643011
TI  - [Mutation analysis of S182 (presenilin-I) in patients with familial Alzheimer's
      disease and its biological function].
AB  - We report the clinical and neuropathologic phenotypes associated with two
      missence mutations in the presenilin I (PS I) gene in Japanese patients with
      early-onset familial Alzheimer's disease. The AM/JPN1 family showed a missense
      mutation (C-->T) which is predicted to cause an Alanine to Valine missense
      substitution at codon 260 (A260V). The disease in the members of this family had
      a mean age-of-onset of 40.3 years old (the range of disease is 8-19 years).
      Neuropathologic studies of two members of AM/JPN1 pedigree showed wide-spread
      senile plaques, neurofibrillary tangles, and neuronal loss, as well abundant
      perivascular subpial amyloid deposits in the Virchow-Robin spaces and Pick-like
      intraneuronal inclusions in the dentate gyrus. In the second pedigree
      transmitting a C-->T nucleotide substitution leading to the missense mutation of
      Alanine to Valine at codon 285 (A285V), the disease had a later age of onset
      (mean, 51 years) but a more rapid course. Comparison of the disease phenotypes
      associated with other missense mutations in exon 9 of PSI reveals no obvious
      clinical or pathological phenotype that uniquely distinguishes Alzheimer's
      disease associated with PS I mutations from other early-onset familial
      Alzheimer's disease. This implies that the variable phenotypes of familial
      Alzheimer's, disease might be attributable to factors other than the PS gene.

PMID- 9643012
TI  - [Positional cloning of susceptibility genes for non-insulin-dependent diabetes
      mellitus].
AB  - Although studies of families and twin studies have demonstrated that non-insulin
      dependent diabetes mellitus (NIDDM) has a strong genetic component, the genes
      responsible for the common forms of NIDDM are largely unknown, due to the complex
      and heterogeneous nature of the disease. To study the genetics of NIDDM, we used
      an inbred animal model of NIDDM, the NSY mouse, in which NIDDM spontaneously
      develops in an age-dependent manner. The inheritance pattern of glucose
      tolerance, fasting insulin levels, insulin response to glucose, body mass index,
      and epididymal fat pad weight in F 1 hybrids of NSY with control C3H/He mice
      suggested the different modes of inheritance in these phenotypes. Multipoint
      linkage analysis of glucose tolerance in F2 mice with microsatellite markers
      throughout the genome mapped at least three loci on different chromosomes.
      Positional cloning of susceptibility genes for NIDDM in NSY mice may increase our
      understanding of the genetics and etiology of human NIDDM and may lead to more
      effective methods for prevention and intervention.

PMID- 9643013
TI  - [Okinawa Longevity Study. Molecular genetic analysis of HLA genes in the very
      old].
AB  - We analyzed HLA class II genes of Okinawan centenarians using the polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to
      identify primary genetic factors in the major histo-compatibility complex (MHC)
      region associated with human longevity. Gene frequencies of centenarians were
      compared with those of normal adults of the same ethnicity who were selected in
      the same vicinity as the centenarians. The following differences were identified
      in the HLA-DQB1 and DQA1 genes: the frequencies of DQB1*0503, DQA1*0101 (04) and
      DQA1*05 were increased in the centenarians, whereas those of DQA1*0102, DQA1*0103
      and DQB1*0604 were decreased. Similarly, for the DRB1 gene, the frequencies of
      DRB1*0101, DRB1*1201 and DRB1*1401 were increased in the centenarians, whereas
      those of DRB1*0403 and DRB1*1302 were decreased. These data suggest that several
      alleles of the HLA-DRB1 and/or HLA-DQ genes are involved in human longevity.

PMID- 9643014
TI  - [Effect of warm bathing on blood pressure in bedridden patients].
AB  - The effects of warm bathing on short-term and circadian rhythms for blood
      pressure (BP), pulse rate (PR), and endocrine function were studied in 10 bed
      ridden patients (5 men and 5 women; age 78.9 +/- 10.5 years old) hospitalized in
      Nomura Municipal Hospital. The results indicated a transient elevation of BP with
      bathing and its rapid fall after bathing. Compared with the days when patients
      did not take bath, systolic BP was significantly lower for 12 to 16 hours (p <
      0.005) after bathing and diastolic BP was also significantly lower during 8 to 12
      hours (p < 0.01), 12 to 16 hours (p < 0.001) and 20 to 24 hours (p < 0.001). The
      PR was significantly higher from 0 to 4 hours after bathing (p < 0.01), but
      became significantly lower during 8 to 12 hours (p < 0.001) and 12 to 16 hours (p
      < 0.001). Plasma renin activity increased significantly after bathing (p < 0.05).
      Thus, the effects of bathing in lowering BP of bedridden patients in stable
      condition may continue for several hours after bathing.

PMID- 9643015
TI  - [An animal model of aspiration and aspiration pneumonia using lacZ gene
      expression in lungs by adenoviral vectors].
AB  - To examine the relationship between disturbed upper airway reflexes and
      aspiration pneumonia, we administered a total volume of 20 microliters of Ad-CMV
      lacZ (Ad vector) or 20 microliters of phosphate buffer solution (PBS) intranasal
      to C57 black mice. In nostrils, the lacZ gene expression was investigated in each
      mouse with or without anesthesia. Under anesthesia, the lacZ gene expression was
      detected by Xgal staining in the lungs of every mouse given the Ad vector.
      However, no gene expression was measured in the lungs of those given the Ad
      vector without anesthesia. In mice treated with PBS, there was no lacZ gene
      expression in the nostrils, trachea, or lungs, irrespective of anesthesia. These
      results suggest that unconsciousness or disturbed upper airway reflexes caused by
      anesthesia caused aspiration, resulting in an intranasal bolus that can reached
      the lower airways. This process can be analyzed in mice tracted with adenovirus
      vectors carrying the E. coli LacZ gene. Mice given Ad-CMV-lacZ transnasally can
      be used to study aspiration pneumonia in relation to unconsciousness.

PMID- 9643016
TI  - [Relationship between cognitive function and discharge place among stroke
      patients after rehabilitation].
AB  - One hundred and ninety-nine elderly stroke patients, who received rehabilitation
      treatment, were examined, to clarify the relationship between cognitive function
      and discharge place. The patients who moved to long-term care facilities showed
      more severe disabilities of basic activities of daily living (ADL), more frequent
      incontinence, and lower functional impairments (Brunnstrom stage), compared with
      those discharged to their home. Multivariate regression analysis was done with
      discharge place as the dependent variable. Independent variables were age, sex,
      kind of stroke, rehabilitation period, level of ADL and IQ on Kohs test, or
      performance IQ on the Wechsler Adult Intelligence Scale. Older age, higher levels
      of ADLs, and higher scores on Kohs test IQ or Wechsler Adult Intelligence Scale
      Performance IQ were all significantly linked with home discharge. These results
      suggest that non-verbal cognitive dysfunction may affect discharge place in
      elderly stroke patients after rehabilitation therapy.

PMID- 9643017
TI  - [Relationships of psychological, physical, blood measurements to EEG findings
      among the aged in nursing home].

PMID- 9643018
TI  - [Sorsby's fundus dystrophy. A genetically homogeneous disease].
AB  - BACKGROUND: The recent identification of the tissue inhibitor of
      metalloproteinases-3 (TIMP3) as the gene underlying SFD pathology has made it
      possible to address the question of genetic heterogeneity in this disorder. In
      addition, it now has become feasible to clarify whether SFD is directly involved
      in other maculopathies and, in particular, may represent a genetic model for age
      related macular degeneration. PATIENTS: Genetic analysis were performed in five
      unrelated and 18 related British SFD pedigrees as well as in 143 patients
      affected with age-related macular degeneration, 28 patients with adult
      vitelliform macular dystrophy, 21 patients with central areolar choroidal
      dystrophy and 25 individuals with other forms of macular dystrophies. RESULTS:
      Molecular genetic analyses confirmed the autosomal dominant mode of inheritance
      in SFD. In all five unrelated SFD pedigrees individual TIMP3 mutations were
      identified introducing an additional cysteine residue into the C-terminal region
      of the mature protein. Affected individuals from 18 SFD families residing in
      Great Britain, Canada, Oregon and South Africa were found to carry a common
      ancestral Ser181Cys mutation. The clinical variability of this Ser181Cys mutation
      was reevaluated. A mutational screen in 217 patients with various maculopathies
      revealed no disease-causing mutations in the TIMP3 gene. CONCLUSION: So far,
      TIMP3 mutations have exclusively been associated with SFD. Therefore, this
      disorder appears to be genetically homogeneous with complete penetrance but
      variable expressivity.

PMID- 9643019
TI  - [Ultrastructural localization of lipid peroxides in the eye. Presentation of a
      new method].
AB  - Lipid peroxidation is considered a prominent feature of age-related retinal
      degeneration. It is known that lipid peroxides can oxidize benzidine. This
      property was used to localize lipid peroxides ultrastructurally in the retina.
      METHODS: (1) Lipid peroxides were formed by incubation of linoleic acid with
      lipoxygenase from soybean, separated by thin layer chromatography and incubated
      with tetramethylbenzidine. (2) Lipid peroxides were formed by incubation of
      porcine retinae with soybean lipoxygenase in an oxygensaturated atmosphere. For
      ultrastructural localization, isolated retinae with and without enzymatically
      synthesized lipid peroxides were fixed with 2% glutaraldehyde, incubated with 0.5
      mg/ml tetramethylbenzidine and embedded for electron microscopy. (3) Eye cups
      from Syrian golden hamsters were treated in the same way except for incubation
      with lipoxygenase. The hamsters were kept under constant illumination (1000 lux)
      for 12 h to enhance lipid peroxidation. RESULTS: (1) Tetramethylbenzidine was
      oxidized by linoleic acid peroxides. (2) In the isolated retinae of pigs lipid
      peroxides became visible as electron-dense structures in the rod outer segments
      (ROS) after treatment with lipoxygenase and were lacking in the other parts of
      the retina. Without treatment with lipoxygenase lipid peroxides were only
      infrequently seen in ROS. (3) In the eyes of light-exposed hamsters, electron
      dense reaction products of lipid peroxides were particularly prominent between
      the basal infoldings of the RPE and within the apical parts of the ROS.
      CONCLUSION: Light or enzymatically induced lipid peroxides can be localized
      ultrastructurally due to their ability to react with tetramethylbenzidine and
      osmium in the absence of H2O2 to an electron-dense reaction product. Lipid
      peroxides seem to be removed from the RPE via Bruch's membrane and blood vessels.
      Disturbance of this pathway may enhance lipofuscin or drusen formation.

PMID- 9643020
TI  - [Choroid neovascularization in age-related macular degeneration. Correlation of
      histological and fluorescence angiography findings].
AB  - BACKGROUND: Recent studies have raised confusion about the fluorescein
      angiographical and histopathological correlation of CNV. MATERIAL AND METHODS:
      The preoperative fluorescein angiograms of four patients with subfoveal CNV due
      to ARMD extracted by pars plana vitrectomy were classified as wellor ill-defined
      CNV and were correlated to the histopathologically (in serial sections) verrified
      CNV-location (subneuroretinal (= type II according to Gass) versus sub-RPE (type
      I according to Gass)). RESULTS: The locations of all four CNV could be classified
      by histopathological landmarks as there were RPE, BLD/drusen, and inner Bruchs
      membrane. Angiographically welldefined membranes were type II membranes according
      to Gass, whereas the ill-defined membrane represented type I. The CNV with well-
      and ill-defined borders consisted of type II and type I parts according to Gass.
      CONCLUSION: We find subneuroretinal locations of the well-defined CNV examined
      (type II membranes according to Gass). Correspondingly, ill-defined CNV or ill
      defined parts of a CNV seem to be beneath the RPE (type I). The correlation of
      fluorescein angiography and histopathology should be studied in greater numbers
      of well- and ill-defined CNV.

PMID- 9643021
TI  - [Adhesion of liquid perfluorocarbon to various intraocular lens materials. A
      light microscopy study].
AB  - INTRODUCTION: Perfluorocarbone liquids (PFCL) enable explantation of intraocular
      lenses (IOL) dislocated into the vitreous. Because of their relatively high
      specific weight, the IOL can be floated off the retina and repositioned in the
      anterior segment. If the IOL surface is affected by contact with PFCL is still
      unknown. We were interested in the extent of PFCL contact with different IOL
      materials, having in mind a repositioning of a dislocated IOL into the posterior
      chamber. We investigated the adherence of PFCL to different IOL surfaces.
      MATERIALS AND METHODS: The following IOL materials were tested: Group I:
      acrylate/methacrylate polymers: (a) PMMA, compression molding; (b) PMMA,
      compression molding, heparin-surface modified; (c) poly-hydroxyethylmethacrylate
      (polyHEMA); (d) phenylethylacrylate, phenylethylmethacrylate; (e)
      methylmethacrylate, HEMA; (f) methylmethacrylate, hydroxyethylmethacrylate,
      ethylene glycol dimethacrylate; (g) hydroxyhexylmethacrylate, HEMA. Group II:
      silicone elastomers: (a) polydimethylsiloxane; (b) polydimethyldiphenylsiloxane.
      A total of 17 types of standard quality IOLs were obtained from several
      manufacturers. Each IOL was immersed in PFCL for 3 h. Then each IOL was rinsed
      with 2 ml balanced salt solution (BSS) and investigated by light microscopy with
      regard to the extent of PFCL adhesion. RESULTS: After rinsing with BSS, no PFCL
      was detectable on any IOL surface. Possible PFCL invasion into an open optic
      haptic junction in three-piece IOLs could not be excluded using this method. All
      IOLs demonstrated optic and haptic surfaces without alterations. The IOL surfaces
      were comparable to those of new IOLs. CONCLUSIONS: With respect to PFCL-IOL
      interaction, all IOLs seem to be inert. After luxation of the IOL into the
      vitreous and IOL elevation by using PFCL, repositioning of the dislocated IOL
      seems to be possible under special conditions (adequate total diameter, IOL
      without damage, no open haptic junction in the optic). After rinsing the
      explanted IOL with BSS prior to reimplantation, the risk of damaging the eye by
      PFCL remnants on the IOL appears neglibile.

PMID- 9643022
TI  - [Intraocular lens implantation in childhood. Functional results and
      complications].
AB  - IOL implantation in childhood is still controversial. INTENTION: The purpose of
      this retrospective study was to evaluate functional results and complications in
      children after IOL implantation. METHODS AND RESULTS: Posterior chamber IOLs were
      implanted in 52 eyes of 45 children. Cataract extraction was necessary because of
      traumatic, congenital/developmental and secondary lens opacities. Nine IOLs were
      implanted in children between the ages of 1.9 and 4 years, 17 IOLs from 4 to 8
      years and 26 IOLs in patients 8 to 14.3 years old. In 38 of the 52 eyes (73%)
      vision improved after the surgery. Fifty-four percent had an acuity of at least
      0.5. The functional results of children more than 8 years old were superior to
      those of younger patients. Children with traumatic cataracts had better visual
      acuities than those with other types of cataract. Except for secondary capsular
      opacities (75%) that could not be prevented by performing a primary posterior
      capsulotomy or capsulectomy and iris capture (31%), postoperative complications
      were rare. CONCLUSION: Favorable functional results can be achieved by IOL
      implantation in children with cataracts. Many patients require secondary surgical
      procedures because of capsular opacities and iris capture.

PMID- 9643023
TI  - [Corneal topography of the partner eye in unilateral keratoconus].
AB  - PURPOSE: To study the incidence and shape of subclinical keratoconus with corneal
      topography in the fellow eye in the case of clinically, slit-lamp
      biomicroscopically and topographically diagnosed unilateral disease. METHODS:
      Eighty patients with keratoconus were fitted with contact lenses. Twelve of them
      revealed clinical features of unilateral disease. In these patients we performed
      a computed topographic analysis in the clinically normal fellow eye. We measured
      quantitative parameters (central corneal power, I-S value) and qualitative
      parameters (localization and shape of corneal steepening). RESULTS: In all 12
      patients we found in the fellow eye no slit-lamp evidence for keratoconus. Nine
      patients were emmetropic in the fellow eye, three patients myopic between -1.5
      and -4.0 D. The myopia in these patients was corrected with contact lenses and
      the investigation was performed 5 days after discontinuance of contact lenses.
      The corneal topography showed the typical keratoconus pattern in 11 patients with
      a steepening of the inferior cornea and in 1 case a superior steepening of the
      cornea; range of I-S values -1.0 to +5.0 D. All patients revealed a configuration
      of oval type cone keratoconus in the corneal topography. CONCLUSION: Keratoconus
      occurs with a high degree of bilaterality, but with onset of the disease at
      different times in the two eyes. Corneal topography seems to be a sufficient
      method to detect early keratoconus.

PMID- 9643024
TI  - [Combined myopia-astigmatism correction. A comparison with pure myopia
      correction].
AB  - BACKGROUND: Myopic PRK up to 6 D is an approved and safe procedure. The efficacy
      and safety of combined treatment of myopia and astigmatism in compound myopic
      astigmatism (PARK) have not yet been demonstrated. PATIENTS AND METHODS: In a
      prospective study in 342 eyes the results of myopic PRK were compared to those of
      correction of compound myopic astigmatism (PARK). RESULTS: Regarding spherical
      refraction achieved there was no significant difference between groups. Best
      corrected visual acuity only improved in the group with high astigmatism; this
      group also showed the least number of Central Islands. Permanent haze and steroid
      induced glaucoma or cataract were not observed after treatment up to 6 D. Average
      astigmatism of 2.24 D was be reduced to 0.53 D 1 year post-operatively.
      CONCLUSIONS: Correction of astigmatism resulted in undercorrection of
      approximately 30%. Our experience with the keracor shows PRK up to 6 D with or
      without additional correction of astigmatism (PARK) to be comparatively safe in
      terms of regression and complications and equally accurate in reaching spherical
      target refraction.

PMID- 9643025
TI  - [Primary orbital implant dislocation. A retrospective study].
AB  - BACKGROUND: To compensate the orbital volume deficit after enucleation orbital
      implants are used. METHOD: Between 1986 and 1996, 449 enucleations were
      performed. One hundred and fifty-five orbital implants were used: 96
      hydroxylapatite-ceramic-silicon (HAK-silicon), 29 hydroxylapatite-ceramic (HAK),
      26 Kiel bone chips, 3 Walser and 1 Bangerter implant. RESULTS: Ten orbital
      implants (6.45%) had to be explanted. Seven of the 96 HAK-silicon implants were
      explanted: four could be changed, two of them with a smaller and two with a same
      diameter. We observed a complication rate of 7.29% and a rate of total loss of
      3.13%. One luxated HAK-implant could be refixated (3.45%), and one implant
      (3.85%) of the Kiel bone chip implants was explanted. CONCLUSION: Using different
      types of orbital implants after enucleation, we observed a complication rate of
      7%. However, to avoid the post-enucleation-syndrome and to achieve better
      motility of the prosthesis, orbital implants should be used.

PMID- 9643026
TI  - [Epidemiology of severe eye injuries. United States Eye Injury Registry (USEIR)
      and Hungarian Eye Injury Registry (HEIR)].
AB  - BACKGROUND: Both in industrialized and in developing nations, the devastating
      impact of ocular trauma on society is increasingly recognized. Lacking
      standardized surveillance systems, however, comparable epidemiological
      information has not been available previously. METHODS: For several years, the
      United States Eye Injury Registry (USEIR) and the Hungarian Eye Injury Registry
      (HEIR) have been collecting data on all types of serious ocular trauma, based on
      identical operating criteria and using standardized reporting forms. We performed
      a retrospective analysis comparing the two datasets, containing over 8,400
      injuries from the U.S. and over 1,200 injuries from Hungary. RESULTS: Sixty
      percent of patients in the U.S. and 52% of patients in Hungary were less than 30
      years of age, with an at least 80% male preponderance in both registries. The
      home was the most frequent place of injury in both countries (USEIR: 41%, HEIR:
      35%); industrial premises represented no more than 14%. Guns were responsible for
      12% of cases in the USEIR (HEIR, 1%). Champagne corks were identified as a unique
      and relatively common source of eye injury in Hungary (1.4%, as opposed to 0.07%
      in the U.S.). In the USEIR, 16% of injuries were caused by assault (HEIR, 24%;
      chi-square value = 36.7, p < 0.0000001). The enucleation rate was 12% in the U.S.
      and 1% in Hungary. CONCLUSIONS: The different findings in the two countries
      identify certain areas for the implementation of preventive measures (supplying
      champagne bottles with warning labels and a coordinated fight against violence in
      Hungary, stricter fireworks legislation in the U.S., public awareness for home
      injuries in both countries, etc.). Based on the encouraging results from this
      study, we plan to continue our efforts using modified reporting forms and an
      upgraded software. We invite additional countries to adopt the USEIR model.

PMID- 9643027
TI  - [Bilateral simultaneous acute amaurosis in neuritis nervi optici. Initial
      manifestation of encephalomyelitis disseminata].
AB  - BACKGROUND: Bilateral simultaneous acute amaurosis as a primary manifestation of
      demyelinating disease is extremely rare. PATIENT: The clinical course of a 24
      year-old patient who initially presented with a bilateral complete loss of vision
      is demonstrated. Morphologically both optic discs appeared slightly blurred and
      prominent. Otherwise there were no anterior and posterior segment abnormalities.
      Examination of the cerebrospinal fluid revealed an increased number of cells and
      protein without oligoclonal bands. On MRI multiple white matter lesions were
      visible. Laboratory tests showed no specific abnormalities, especially with
      respect to infectious or vasculitic diseases. Under intensive steroid therapy
      (initially 1000 mg prednisolone/day), visual acuity recovered almost completely.
      Nine months after onset of the disease visual acuity was 1.0 in both eyes.
      CONCLUSIONS: Even in patients with a fulminant onset of the disease almost
      complete visual recovery is possible. Differential diagnosis should rule out
      vasculitic autoimmune optic neuritis, infections, tumors, processes of the
      paranasal sinuses, toxic, and hereditary causes.

PMID- 9643028
TI  - [Bilateral retinal tumors in a child. Tuberous sclerosis with retinal
      astrocytomas].

PMID- 9643029
TI  - [Development of the filtering bleb after trabeculectomy. Classification,
      histopathology, wound healing process].

PMID- 9643030
TI  - [Orthodontics in the 21st century: a multidisciplinary].

PMID- 9643031
TI  - [An interview with Dr. Vincent Kokich. Interview by Sophie Rozencweig].

PMID- 9643032
TI  - [An interview with Pr. Annika Isberg. Interview by Georges Rozencweig].

PMID- 9643033
TI  - [An interview with Pr. Sandro Palla.. Interview by Gerard Lebre].

PMID- 9643034
TI  - [Occluso-orthodontic course].

PMID- 9643035
TI  - [Articular surgery in the treatment of temporomandibular dysfunction].
AB  - The temporomandibular joint surgery is developing towards less invasive
      procedures. Open surgery provides a lot of complications. Arthroscopy is now
      almost the only common used procedure, especially lysis and lavage.
      Arthrocentesis provides good results too. However, careful preoperative and
      appropriate nonsurgical care are essential. Only 5 and 7% of the patients who are
      treated for TMJ disorders and dentofacial deformity, TMJ surgery precedes
      surgical/orthodontic treatment.

PMID- 9643036
TI  - [Occlusion and dysfunction: the paradox of dentofacial orthopedics].

PMID- 9643037
TI  - [MRI study of temporomandibular joint disk behavior in chilren with
      hyperpropulsion appliances].
AB  - Orthodontic and orthopaedic effects of hyperpropulsors have been studied,
      evaluating the possible adaptation of the temporo mandibular joint. Before the
      event of MR imaging, the positional modification of the disc could not be seen.
      The study has been carried out on 15 subjects, skeletal Class II, with a mean age
      of 11.6 years (SD = 1 year). A bilateral MR investigation has been done before
      and after the wear of an activator (Herbst or Monobloc with Head Gear). All
      patients underwent bilateral imaging in sagittal and modified coronal planes in
      closed and opened mouth. The qualitative analysis of the temporo-mandibular
      joints reveals the appearing of internal derangements, often asymptomatic, in one
      case out of five; the disc being anteriorly displaced on an average of 8.3
      degrees (p = 0.023). These results need to be confirmed on larger samples but may
      modified functional approach of orthopaedic treatments in order to take into
      account the TMJ change.

PMID- 9643038
TI  - [The development of craniomandibular disorders after bilateral sagittal
      osteotomy].
AB  - The aim of this study is to know the repercussions of modified sagittal ramus
      split osteotomy of the mandible on the anamnesic symptoms of cranio-mandibular
      disorders in 89 patients. The sample was divided into different groups according
      to the surgery type: mandibular advancement or mandibular retrusion with or
      without maxillary surgery. The anamnesic approach allows to evaluate the felt
      symptoms. All had a surgery by the same surgeon and with the same technique:
      mandibular sagittal bilateral surgery according to the modificated Obwegeser
      osteotomy. The statistical analysis shows some differences between groups.

PMID- 9643039
TI  - [An interview with Dr. Robert L. Boyd. Interview by Christian Demange].

PMID- 9643040
TI  - [An interview with Dr. Henry Salama. Interview by Gerard Lebre].

PMID- 9643041
TI  - [Clinical attitudes toward periodontal risk].
AB  - After having defined the conditions that will start the loss of attached gingiva,
      the author develops the characteristic of the patient at periodontal risk. He
      then explains the value of the interview as well as that of the clinical and
      microbiological exams, insisting on the therapeutic outcome of those exams, and
      on the effect of the flora.

PMID- 9643042
TI  - [Conditions of the successful outcome of mucogingival surgery during orthodontic
      treatment].
AB  - For the last twenty years the mucogingival surgical technics, particularly
      displaced flaps, have brought gingival tissue when it is missing improving the
      periodontic outcome of orthodontic treatment. The displaced flaps are indicated
      where is a deficient attached gingiva or for uncovering retained cuspids. This
      state of the art is done both for the surgical and orthodontic care that are
      necessary as well as for the possible problems and complications after surgery.

PMID- 9643043
TI  - [The importance of periodontal evaluation in orthodontics].
AB  - The orthodontist is in fact a periodontal-therapist since his aim is to move the
      teeth with and through the periodontal tissues. It is most important for the
      orthodontist to be able to determine at the initial clinical examination what are
      the various periodontal risk factors. When the pathology is obvious with
      inflammation, periodontal pockets, gingival hyperplasia, edema of the papillae,
      gingival recessions, the need for periodontal treatment is manifest. But many
      times, the periodontal evaluation is complicated by the presence of slight
      variations of the quality of the marginal tissue that represent a risk of
      developing periodontal defects during the orthodontic treatment. The aim of this
      presentation is to put forward the importance of the periodontal evaluation
      during the initial examination of the patient so that, if necessary, an adequate
      periodontal therapy can be initiated to stabilize the periodontal tissues and
      thus improves the esthetical outcome.

PMID- 9643044
TI  - [Pre-orthognathic surgery in orthodontics: towards justification].
AB  - This work presents long term results of rhinopharyngeal desobstructions on nine
      years old patients. By using several techniques such as: tonsillectomies,
      adenoidectomy, adenoidotonsillectomies, luxation of inferior turbinates, partial
      turbinectomies or bilateral turbinectomies under endoscopic guidance, and then,
      following carefully the oral and nasal peak flows for a period as long as one or
      two years, it becomes obvious that the most efficient desobstruction procedure is
      accomplished through a combination of E.N.T. rhinopharyngeal procedures, i.e.
      adenoidotonsillectomies and inferior turbinectomies under endoscopic guidance.
      This global E.N.T. procedure is known as "Chimney Sweep". The author demonstrates
      that tongue behavior is severely affected by rhinopharyngeal obstruction and by
      the consecutive dysfunction of the upper airway ventilation pattern. Large
      tongues and normal tongues pushed forward due to enlarged tonsils or adenoids are
      also affected by their necessary participation to oral ventilation (mouth
      breathers). Addition of a selective lingual glossoplasty or a partial glossectomy
      is sometimes necessary to put the morphogenic function in a proper order during
      growth and development. All of the above is part of a new pre-orthognathic
      concept, that helps control growth and development and helps manage orthodontic
      or orthognathic treatments.

PMID- 9643045
TI  - [The role fo function in the growth of form].
AB  - The cranio-facial shape is the outcome of growth, unequally influenced by
      heredity and environment. Even if limited, the influence of function is certain,
      and results essentially from neuromuscular behavior. This relationship imposes
      the taking into account and correction of any functional abnormality by training,
      during the correction of malocclusions.

PMID- 9643046
TI  - [Arguments apropos of surgery of orofacial functions].

PMID- 9643047
TI  - [An interview with the maxillofacial surgeon G. William Arnett. Interview by
      Colette Orival-Demange].

PMID- 9643048
TI  - [An interview with Dr. W.H. Bell and Dr. C. Mannai. Interview by Colette Orival
      Demange].

PMID- 9643049
TI  - [Regarding orthognathic surgery].
AB  - The author scrutinises the evolution of orthognathic surgery for the last twenty
      years through the different parameters that participate to its origin; esthetic
      motivation, orthodontico-surgical collaboration, the limitation of widely used
      technics, a simple surgical solution, the spreading of rigid fixation, the
      interest of primary or secondary genioplasty, the consideration of ethnic
      differences,the usefulness of a maxillo-facial chain, the possible retreatment of
      failures and consideration for the stability of results.

PMID- 9643050
TI  - Mismatch negativity in dichotic listening: evidence for interhemispheric
      differences and multiple generators.
AB  - The characteristics of mismatch negativity (MMN) elicited by dichotic stimulation
      were examined using frequency-deviant stimuli presented to the right, to the
      left, or to both sides. The experiment was run twice, once using earphones and
      once using loudspeakers in free field. With both modes of stimulation, deviants
      presented in the left, right, or both ears, or tones that were switched between
      ears, elicited comparable MMNs, with a peak latency of about 180 ms. With
      earphones, the amplitude of the MMN was bigger at the frontal-lateral right
      hemisphere sites than at the homologous left-hemisphere sites for all deviance
      conditions. Scalp current density analysis revealed that deviance in the right
      side elicited bilaterally equivalent frontal current sinks and a trend towards
      stronger contralateral current sources at the mastoid sites. In contrast, left
      side deviance elicited frontal sinks and temporal current sources stronger over
      the right hemiscalp. These results are compatible with the multiple-generator
      model of MMN. The attention-related role of the MMN is discussed, suggesting
      comparable attention mechanisms for vision and audition.

PMID- 9643051
TI  - On the automaticity of ipsilateral response activation in the Simon effect.
AB  - The effects on performance of unattended stimulus-response spatial relationships
      in choice reaction time tasks (i.e., the Simon effect) have been attributed to
      automatic activation of the response ipsilateral to stimulus location. We tested
      this assumption using the lateralized readiness potential (LRP). The response key
      labels changed randomly from trial to trial and were presented either 400 ms
      before (immediate-reaction trials) or 400 ms after (delayed-reaction trials)
      stimulus. The critical test for the automatic activation hypothesis was on
      delayed-reaction trials, in which LRP deflections were expected in the interval
      between stimulus and response-key labels. Contrary to this prediction, there were
      no LRP signs of response activation within that interval.

PMID- 9643052
TI  - Frontal brain asymmetry and affective style: a conceptual replication.
AB  - Recent studies have demonstrated that positive and negative affective reactivity
      can be predicted by resting electroencephalographic (EEG) asymmetry in frontal
      brain regions. These studies used different methods to assess asymmetry and
      affectivity. The goal of the present study was a conceptual replication of these
      results and to investigate their independence of employed procedures. Resting EEG
      of 37 subjects was recorded and affective slides were presented to obtain ratings
      of subjects' emotional reactions. Different procedures were applied to the data
      to assess the relation between asymmetries and affective reactivity. Depending on
      the particular analysis procedure, there were associations between anterior
      asymmetry and affectivity in line with the published findings, opponent to those
      findings, or no relation between anterior asymmetry and affective reactivity.

PMID- 9643053
TI  - Resting frontal electroencephalographic asymmetry in depression: inconsistencies
      suggest the need to identify mediating factors.
AB  - Two studies of the relationship between depression and resting frontal
      electroencephalographic (EEG) activity are reported. Although considerable
      research supports the theory of left and right hemispheric specialization for
      approach and withdrawal behaviors, only four studies involving clinically
      depressed individuals have been published to date. Despite methodological
      similarities with published research, no significant differences in frontal
      activation emerged between depressed and nondepressed participants with either
      college students having high Beck Depression Inventory scores (Study 1) or with
      individuals diagnosed with DSM-III-R depression (Study 2). Post hoc analyses in
      Study 2 revealed one effect confined to lateral frontal leads during the first 2
      min of EEG data; this finding was significant in only one of three reference
      montages. Results are discussed in light of methodological considerations and
      mediating variables such as temperament and coping styles.

PMID- 9643054
TI  - Effect of feedback signal and psychological characteristics on blood pressure
      self-manipulation capability.
AB  - Blood pressure presentation mode and personality are likely to influence
      biofeedback outcome. Thirty-six normotensive subjects were randomly assigned to
      visual or auditory continuous systolic feedback. "Distracting speech" and "broad
      band noise" were also superimposed and the effect on the biofeedback response was
      investigated. Psychological influence was also investigated. Systolic pressure
      reduction of 4 +/- 4.3 mmHg (visual, p = .04) and 5 +/- 5.5 mmHg (visual +
      auditory, p = .03) were achieved compared with auditory feedback (2 +/- 4.7
      mmHg), which was less effective. The addition of noise or speech had no effect on
      the systolic response, but speech adversely affected diastolic reduction (p =
      .04). Mood (p = .003) was associated with systolic lowering, whereas increased
      trait anxiety (p = .06) and expectation (p = .03) had trends for opposite
      effects. Increased anger-hostility, state-anxiety, and expectation (p = .06) had
      links with systolic raising capability. We conclude that feedback modality and
      psychological characteristics have implications for studies investigating blood
      pressure manipulation capability.

PMID- 9643055
TI  - Automatic change detection: does the auditory system use representations of
      individual stimulus features or gestalts?
AB  - The effects of global and feature-specific probabilities of auditory stimuli were
      manipulated to determine their effects on the mismatch negativity (MMN) of the
      human event-related potential. The question of interest was whether the automatic
      comparison of stimuli indexed by the MMN was performed on representations of
      individual stimulus features or on gestalt representations of their combined
      attributes. The design of the study was such that both feature and gestalt
      representations could have been available to the comparator mechanism generating
      the MMN. The data were consistent with the interpretation that the MMN was
      generated following an analysis of stimulus features.

PMID- 9643056
TI  - Influence of respiratory activity on the cardiac response pattern to mental
      effort.
AB  - A group of 32 healthy adult volunteers completed three blocks of a reaction time
      task that varied in the degree of controlled processing load. A rest period
      preceded each of the task blocks. The task blocks were presented in the order of
      either increasing or decreasing cognitive load. For each of the six periods, mean
      values and spectral measures of heart rate and respiration variability were
      calculated. The spectral measures were obtained for three different frequency
      bands. Differences between the cardiac measures of the task and preceding rest
      periods were compared with respect to differences in task load and the order of
      task presentation. All comparisons were carried out while adjusting for
      respiratory variability in the corresponding frequency band. The frequency band
      in which task load-related changes in heart rate variability became manifest
      appeared to be dependent on the individual's breathing pattern.

PMID- 9643057
TI  - Scaling of movement velocity: a measure of neuromotor retardation in individuals
      with psychopathology.
AB  - The study of motor slowness based on observational methods has limitations.
      Whether motor retardation has a psychomotor or neuromotor basis is unclear
      because psychiatric and motor symptoms overlap. Observational methods lack the
      precision necessary to distinguish cognitive from motor processes. For the
      present study, we used an objective measure of neuromotor dysfunction to quantify
      the extent to which an individual programs movement velocity in anticipation of
      increasing target distance. Persons with Parkinson's disease (PD) or functional
      psychosis were studied with a group of healthy comparison subjects. Results
      indicated that the slope of the linear function relating velocity to distance was
      abnormal in the PD group and in approximately half of the psychosis group.
      Analyses revealed the measure to have high specificity and sensitivity. Weak
      correlations between velocity scaling and psychopathology support the neuromotor
      basis of the measure. We conclude that this measure of velocity scaling is
      relatively uninfluenced by cognitive factors that may underlie psychomotor
      retardation.

PMID- 9643058
TI  - Maternal exposure to influenza in pregnancy and electrodermal activity in
      offspring: a further study from Mauritius.
AB  - This study examined the effect of mothers' exposure to the 1957 A2/Singapore
      influenza virus in the first, second, and third trimesters of pregnancy on the
      electrodermal activity of their 15-year-old offspring. The epidemic occurred
      during cold months of the year. The results show that maternal viral (and cold)
      exposure during all trimesters of pregnancy produced a lower frequency of
      nonspecific electrodermal responses and diminished responsivity to 75-db and 90
      db tones as compared with the offspring of mothers who were not exposed. However,
      there was a critical effect of second trimester exposure as indicated by an
      increase in frequency of nonresponses to orienting tones. The findings are
      compared with those from an earlier study from Mauritius involving 3-year-old
      children in which the effects of exposure to the 1968 A2/Hong Kong virus were
      examined and in which the effect of could exposure could be examined separately
      because viral exposure occurred during the hot months.

PMID- 9643059
TI  - A longitudinal analysis of eye tracking dysfunction and attention in recent-onset
      schizophrenia.
AB  - The effect of an attentional manipulation on eye tracking dysfunction (ETD) in
      the early stages of schizophrenia was examined in 34 recent-onset schizophrenic
      patients and 24 demographically matched normal subjects over a 1-year period. An
      attentional enhancement manipulation improved eye tracking performance of recent
      onset schizophrenic patients more than that of normal subjects. Eye tracking
      level also was moderately stable for both groups over the course of 1 year. The
      possible role of attentional allocation in ETD highlights the need for further
      examination of the interface between attentional and eye tracking measures of
      vulnerability to schizophrenia.

PMID- 9643060
TI  - Effects of stimulus modality and task condition on blink startle modification and
      on electrodermal responses.
AB  - Participants in Experiments 1 and 2 performed a discrimination and counting task
      to assess the effect of lead stimulus modality on attentional modification of the
      acoustic startle reflex. Modality of the discrimination stimuli was changed
      across subjects. Electrodermal responses were larger during task-relevant stimuli
      than during task-irrelevant stimuli in all conditions. Larger blink magnitude
      facilitation was found during auditory and visual task-relevant stimuli, but not
      for tactile stimuli. Experiment 3 used acoustic, visual, and tactile conditioned
      stimuli (CSs) in differential conditioning with an aversive unconditioned
      stimulus (US). Startle magnitude facilitation and electrodermal responses were
      larger during a CS that preceded the US than during a CS that was presented alone
      regardless of lead stimulus modality. Although not unequivocal, the present data
      pose problems for attentional accounts of blink modification that emphasize the
      importance of lead stimulus modality.

PMID- 9643061
TI  - Physiological response to a minimal social encounter: effects of gender,
      ethnicity, and social context.
AB  - This study examined physiological response to an encounter with and touch by an
      unfamiliar person. Fifty-five African American (23 male, 30 female) and 51
      European American (23 male, 28 female) undergraduates participated. A Black or
      White interactor entered the room, introduced himself or herself, checked
      equipment for 30 s, and then took a pulse for 30 s. Entry of the interactor
      resulted in increased corrugator and zygomaticus facial muscle activity (EMG),
      increased skin conductance (SC), and heart rate (HR) acceleration. Corrugator EMG
      was greater among Black subjects; White subjects responded with more zygomatic
      EMG and SC and greater HR acceleration. Women showed a more positive facial
      expression than did men. Being touched reduced EMG and HR but resulted in
      increased SC. White and Black males showed more HR acceleration when encountering
      a Black male interactor.

PMID- 9643062
TI  - Testing treatment effects in repeated measures designs: an update for
      psychophysiological researchers.
AB  - In 1987, Jennings enumerated data analysis procedures that authors must follow
      for analyzing effects in repeated measures designs when submitting papers to
      Psychophysiology. These prescriptions were intended to counteract the effects of
      nonspherical data, a condition know to produce biased tests of significance.
      Since this editorial policy was established, additional refinements to the
      analysis of these designs have appeared in print in a number of sources that are
      not likely to be routinely read by psychophysiological researchers. Accordingly,
      this paper includes additional procedures not previously enumerated in the
      editorial policy that can be used to analyze repeated measurements. Furthermore,
      I indicate how numerical solutions can easily be obtained.

PMID- 9643063
TI  - [Women, human rights and health].

PMID- 9643064
TI  - [Water fluoridation in the Region of Murcia].
AB  - BACKGROUND: The purpose of this study is that of expounding upon the natural
      fluoride ion concentrations in the public water supplies of all of the
      municipalities in the Region of Murcia in 1991, in addition to the trend in said
      concentrations throughout the 1992-1996 period, this being a time during which
      fluoride was added to the water supply as a public health measure. METHODS: The
      methods employed for the findings were those of potentiometer-based gauging by
      means of standard addition and direct findings using a potentiometer equipped
      with an ion-selective electrode. RESULTS: The findings indicate that major
      fluctuations have taken place in the amounts of fluoride in these waters
      throughout the initial years during which fluoride was added to the water supply,
      without it being possible to establish broad-scope geographical patterns, to
      later tend toward stabilization during the final years of the time period in
      question, in which solely the municipalities supplied by the Letur treatment
      plant (which supplies the central and northwestern areas of the Region) showed
      levels nearing 0.8 mg/l, been maintained, which are those stipulated under the
      regulations resolving in favor of the addition of fluoride. CONCLUSIONS: We can
      conclude that only a portion of the municipalities of the Murcia Region has
      reached the optimum value for the concentration of fluoride in drinking water
      proposed by the Autonomous Community (0.8 mg/liter), or values close to it (0.6
      0.7 mg/liter) during the period studied.

PMID- 9643065
TI  - [Readmission rate at a regional hospital].
AB  - BACKGROUND: The purpose of this study is that of describing the frequency of re
      admissions at the "Punta de Europa" Hospital in Algeciras. METHODS: The source of
      information employed was that of the Minimal Basic Hospital Admission Data Set
      (MBHADS) for 1995-1996, a total of 24,613 cases of hospitalization being
      analyzed. Re-admission has been defined as any admission entailing an identical
      major diagnosis within the 30 days following release from the hospital. A
      descriptive analysis has been made of the variables of age, sex, the unit/ward to
      which admitted and major diagnosis involved employing conventional single
      variable techniques. RESULTS: The 30-day re-admissions rate was 5% (IC95% 4.8
      5.2), totaling 3.4% (IC95% 3.2-3.6) if only the emergency re-admissions are taken
      into account. A higher probability of re-admission is related to males, to an
      older age to certain diagnoses and to the units/wards to which admitted. The
      units/wards showing the highest percentage of re-admissions were the Psychiatric
      Ward, Hematology and the Otolaryngology. The Units/Wards showing the lowest
      percentages of re-admissions were Ophthalmology, Traumatology and Obstetrics. The
      most frequent re-admissions diagnoses were: impending childbirth, AIDS and
      complications thereof, neoplasia of the bladder, unstable angina pectoris and
      paranoid schizophrenia. CONCLUSIONS: Hospital re-admissions are a useful
      indicator of the quality of health care which must be continued to be researched
      in our country, particularly after its having been included as an indicator of
      the public hospital program contracts in Andalusia. It is also deemed necessary
      to improve the definition of re-admission in said program contracts.

PMID- 9643066
TI  - [Quality and characteristics of antibiotics prescriptions in an emergency
      hospital service].
AB  - BACKGROUND: To assess the quality of the prescribing of antibiotics to patients
      treated at a hospital emergency department (HED). METHODS: Retrospective study of
      the 8600 patients treated and released from a HED throughout the January-April
      1996 period. Those patients for whom antibiotics were prescribed as stated on the
      release form were included. The parameters employed for assessing the prescribing
      quality were: illness subject to being treated with antibiotics, proper
      antibiotic, dosage, proper frequency and length of time over which the antibiotic
      is to be taken. Each one of these parameters was assigned a mark affording the
      possibility of quantifying quality on a 0-100 point scale. The assessment of the
      extent to which proper treatment was prescribed was made based on the
      recommendations described on four guides to the use of antibiotics. RESULTS:
      Antibiotics were prescribed to 609 (7.1%) of the patients, basically for treating
      urinary tract infections (17.7%), the prevention of wound infection (13.1%) and
      for the treatment of repeated attacks of chronic obstructive pulmonary disease
      (COPD) (10.3%). The antibiotic most often prescribed was cloxacillin (22.5%),
      followed by ciprofloxacin (13.4%) and clarithromycin (13.2%). Of all of the
      patients treated with antibiotics, 10.8% had no illness or any indication subject
      to being treated with these medications, and 32% of those patients who did indeed
      meet these requirements were prescribed an unsuitable antibiotic. Pneumonia was
      the illness for which the best quality of treatment was provided. The average
      mark for the prescriptions did not total 80 points in any of the guides.
      CONCLUSIONS: Antibiotics are medications frequently prescribed in HED's. Major
      errors are found to exist with regard to the indication, selection and length of
      the treatments initiated with these medications, as a result of which it is
      advisable that sustained educational measures be taken.

PMID- 9643067
TI  - [Coverage and immune response to hepatitis B vaccine in adolescents of the
      Guadalajara province].
AB  - BACKGROUND: Hepatitis B comprises one of the major health problems worldwide. One
      of the measures for the prevention thereof is the massive vaccination of
      adolescents. The purpose of our study is that of assessing the degree of coverage
      of the systematic hepatitis B prevention campaign among the 8th-grade population
      in the province of Guadalajara in addition to studying the immune response of
      said population, relating said response to other variables. METHODS: Cross
      sectional study. The degree of coverage of the vaccination campaign was studied
      throughout the entire target population in the province in question. For the
      study of the immune response, a sample of 338 students was taken by systematic
      random sampling. The titres of anti-HB's were quantified 6 months following the
      third dosage, levels of 10 mU/ml or above being considered as being levels
      providing protection. RESULTS: The percentage of students properly vaccinated
      totaled 82.7%. The overall serum protection rate was 97.5%, and 46.7% of the
      sample responded showing titres of over 100 mU/ml. A statistically significant
      inverse relationship (p < 0.001) existed between the level of anti-HB's and the
      Quetelet level, we not having found any significant differences between the two
      sexes on comparing the postvaccination titres of anti-HB's. CONCLUSIONS: We
      consider the degree of coverage provided to be satisfactory and the immunogenic
      aspect of the vaccine to be good. Obesity is a factor providing a prior
      indication of a minor response to the same. This response is not influenced by
      the subject's sex.

PMID- 9643068
TI  - [Occupational accidents at an Acute Care Hospital].
AB  - BACKGROUND: To obtain a better knowledge of the determining factors and
      circumstances giving rise to occupational accidents will foster the
      implementation of corrective measures. The aim of this study is that of
      describing the trend of occupational accidents (OA's) over the course of time and
      of determining the risk factors regarding workers being forced to take time off
      for sick leave at the "Dr. Peset" Hospital in Valencia. METHODS: Description and
      retrospective analysis of the occupational accidents having occurred at the "Dr.
      Peset" Hospital in Valencia throughout the 1992-1995 period. The trend and
      seasonality of the series (seasonal indexes, SI's) were estimated by
      deterministic methods. A logistic regression model was employed to identify the
      factors providing a prior indication workers being off on sick leave and to
      determine the probability of the occurrence thereof. RESULTS: The highest OA
      rates were found among the kitchen and laundry workers (10.00 OA's per 100
      workers/year). The OA's involving sick leave continued to show a trend of around
      zero, February being the months showing the highest SI (SI = 139.8). Those
      processed without sick leave showed an upward trend (r2 = 0.23, p < 0.0001), May
      being the month involving the largest number of casualties (SI = 134.2). The
      probability of an accident resulting in a worker being forced to take time of for
      sick leave increases significantly with age, when the accident in question takes
      place in the afternoon/evening, if it takes place in the kitchen/laundry, and if
      a sprain or tendinitis is involved. CONCLUSIONS: The measures taken involving the
      number of casualties entailing OA's which result in temporary incapacity should
      revolve around the less-skilled positions and the kitchen and laundry
      departments.

PMID- 9643069
TI  - [Analysis of a disease outbreak of brucellosis in slaughterhouse workers].
AB  - BACKGROUND: The appearance of an exceptional number of cases of Brucellosis at
      the end of 1996 in workers at a slaughterhouse led us to suspect an epidemic
      outbreak among this group. This study shows the methodology followed in the
      analysis of this outbreak as well as the results obtained. METHODS: 1.
      Epidemiological description of the outbreak: number of animals with brucellosis
      slaughtered, collection of information from different sources on the number of
      those affected: from the mutual insurance company, the record of working days
      lost, an epidemiological monitoring system and a survey amongst the workers. 2.-A
      case and control study was designed in order to determine, firstly, non
      occupational risks--ingestion of fresh cheese or milk and care of animals--and
      secondly, occupational risks, depending on the job normally undertaken. 3.-To
      verify this a retrospective cohort study was designed. The exposed group was made
      up by workers in the slaughter area and the unexposed group comprised the
      remainder: any worker giving a positive result to the Rose of Bengal test and IgM
      brucellosis antibodies in serum was considered as a case. RESULTS: The
      description of the outbreak enabled us to establish that the cases occurred at
      the moment when most animals were slaughtered, that only occupational risks were
      relevant, that there were more symptomatic cases than notified ones, and that the
      slaughter line operators showed higher rates of attack than the remainder of the
      workers. CONCLUSIONS: This study analyses the possible causal relationship
      between analyzed exposure and the appearance of cases of brucellosis in workers-
      a fact which backs the existing scientific evidence on the importance of the
      respiratory tract as a mechanism of transmission of this disease in the
      workplace.

PMID- 9643070
TI  - [Food habits of school children in a Cordoba health district].

PMID- 9643071
TI  - [Prevalence of anemia in pregnancy, Pucallpa Regional Hospital, Peru].
AB  - Population based health surveys in Peru show that the general fertility rates,
      proportion of pregnant adolescents, and maternal and child morbidity are higher
      in the jungle regions than in other parts of the country. Endemic intestinal
      parasitic diseases increase the risk of anemia in pregnant women already
      suffering from iron, folic acid, and other nutritional deficiencies. This is the
      most common complication of pregnancy in many Latin American countries and is
      often associated with premature labor, low birthweight, and perinatal mortality.
      There are very few studies on this subject based on jungle populations and no
      reliable estimates of the prevalence of anemia in local pregnant women. The
      present study was designed to determine the prevalence of anemia in pregnant
      women attending the Regional Hospital in Pucallpa, located in the Peruvian
      jungle, from January 1993 to June 1995. This cross-sectional study, which was
      based on the registries of prenatal and childbirth services encompassing 1,015
      pregnant women, looked into the potential association between anemia and such
      variables as the mother's chronological age, schooling, previous pregnancies, and
      weight at the beginning of pregnancy. Maternal hemoglobin levels were compared
      with the newborns' weight at birth. The prevalence of anemia in this population
      sample was 70.1%. This value was not modified when adjusted for maternal age,
      schooling, or interval between births. Anemia prevalence was directly related to
      the number of previous pregnancies and inversely related to weight gain during
      pregnancy. The perinatal mortality rate was 37.7 per 1,000 births. Neither this
      rate nor the birthweights were associated with the mother's degree of anemia. A
      multivariate regression analysis showed that maternal body weight at the start of
      pregnancy (P = 0.0001), weight gain during pregnancy (P = 0.0001), and the number
      of pregnancies (P = 0.008) are predictors of birthweight. Results showed that the
      high prevalence of anemia in Pucallpa's pregnant women is not associated with low
      birthweight or a high perinatal mortality rate. Future studies should investigate
      the principal causes of anemia in the pregnant women of Pucallpa and how the
      disease affects the psychomotor development of their offspring.

PMID- 9643072
TI  - [Perceptions regarding leprosy and resulting handicaps prior to diagnosis in
      Recife, Brazil].
AB  - This article reports on a case-control study conducted in Recife, Brazil, between
      November 1993 and July 1994, to determine how leprosy patients' perceptions and
      notions influence disease management and use of health services. The sample was
      composed of 183 residents of Recife between the ages of 20 and 70 years who
      sought diagnostic services in the dermatology clinics of two referral centers
      situated in the third, fourth, and sixth political and administrative regions.
      Sixty-four patients having handicaps or their precursor lesions were classified
      as cases; the remaining 119 were used as controls. All were diagnosed during the
      study period. For the analysis, adjustments were made for sex, age, schooling,
      and a previous history of Hansen's disease among patients. The study revealed the
      simultaneous presence of two types of "invisibility" of the disease in an area
      where endemicity is increasing: 1) for patients in both groups, the low frequency
      of spontaneous explanatory models related to the illness, even in the presence of
      disease, and 2) for health professionals, the limitations of detection methods.
      Since such deficiencies affect decisions bearing on individual and collective
      disease management, they are a risk factor in and of themselves and stand in the
      way of eliminating leprosy as a public health problem.

PMID- 9643073
TI  - The use of capture-recapture methods to monitor diabetes in Dominica, West
      Indies.
AB  - The aim of this project was to evaluate the utility of capture-recapture (CR)
      estimation methodology, together with easily accessible sources of information,
      for monitoring the frequency of diabetes mellitus in a developing country. On the
      Caribbean island of Dominica, from July 1995 through July 1996, the names were
      collected of all individuals who were listed in at least one of three sources as
      having been diagnosed with diabetes during 1995. The sources were the membership
      list of the Dominica Diabetic Association, a register of patients in seven
      regional health centers, and clinic records of the Princess Margaret Hospital,
      which is the main hospital on the island. Capture-recapture techniques were used
      to estimate the number of Dominicans with diagnosed diabetes who were missed by
      all three sources of information and to evaluate dependencies among the sources.
      An ascertainment-corrected prevalence estimate of diagnosed diabetes was then
      calculated. The three sources identified a total of 1,945 different individuals.
      When this number was compared with the ascertainment-corrected estimate obtained
      with CR methodology (2,688), it appeared to represent only 72.3% of the true
      prevalence of diagnosed diabetes. Most of the under-ascertainment by the data
      sources was due to cases that were missed in the urban area of the island. This
      approach to disease monitoring may be useful for other Caribbean countries.
      However, standardized procedures for collecting and reporting prevalence and
      morbidity data are needed to maximize its accuracy and cost-effectiveness.

PMID- 9643074
TI  - [Cytopathological test coverage in the city of Pelotas, Brazil].
AB  - In 1995, cervical cancer was the fourth most important cause of death among women
      in the state of Rio Grande do Sul, Brazil. There are no available studies on Pap
      smear examination coverage in Pelotas, which is the largest city in the southern
      part of Rio Grande do Sul. Accordingly, in 1992 a population-based, cross
      sectional study was carried out among 20 to 69 year-old women residing in urban
      areas of the city. The objectives of the study were to ascertain any Pap smear
      testing in the 3 years prior to the study, to determine the coverage of cervical
      cancer screening, and to identify any factors associated with the performance of
      Pap tests in Pelotas. Social class was chosen as the determining variable. To
      categorize social class, two classifications were used: Bronfman's classification
      and the classification used by the Brazilian Association of Market Research
      Institutes. Among the 934 women interviewed, 606 (65%) had had a Pap smear test
      in the 3 years before the study. The multivariate analysis revealed significant
      differences regarding performance of such tests in terms of social class, age,
      and frequency of medical consultations per year. No significant differences were
      found in terms of education, type of health service used, or hospitalizations
      during the year prior to the study. This study reveals that coverage of cervical
      cancer screening for women between 20 and 69 years of age in Pelotas is higher
      than the coverage found in other parts of the country or even of the world.
      However, for women in lower social classes, coverage was found to be between 52
      and 56%. These data can contribute to the development of measures aimed at
      increasing cervical cancer screening among specific sectors of the population.

PMID- 9643075
TI  - [Risk factors for low birth weight].
AB  - Low birthweight (LBW) is the main known determinant of infant mortality. In spite
      of the sharp decrease in infant mortality rates and of the rise in survival rates
      for children with LBW, no important decrease in LBW rates has been observed in
      Neuquen, Argentina. The purpose of this study was to try to understand the risk
      factors for LBW, the frequency of LBW in the population, and the role of prenatal
      care in its prevention, as well as to develop a risk factor scale that could be
      used to identify women at higher risk of giving birth to a child with LBW. With
      this in mind we performed a cross-sectional study based on 50% of the data
      entered into the Perinatal Information System for 1988-1995 by the 29 hospitals
      in Neuquen province (46,171 births). The distribution of birthweight and the
      frequency of potential risk factors for LBW were examined. The relationship
      between such factors and LBW was studied using a logistic regression model. On
      the basis of the results obtained, an additive scale was drawn up and validated
      with the remaining 50% of the data for registered births. The highest odds ratio
      (OR) was seen in women who had no prenatal care (OR = 8.78; 95%CI: 6.7 to 11.4).
      ORs for inadequate prenatal care, lateness in attending the first prenatal visit,
      preeclampsia or eclampsia, hemorrhage and anomalies of the placenta or placental
      membranes, and a history of a previous child with LBW were greater than 2.0. The
      risk of having children with LBW was also higher in women over the age of 40,
      women under 20, single women, smoking mothers, women with an intergenesic
      interval of less than 18 months, and women with a body mass index of less than
      20. Finally, there was a direct linear relationship between points on the risk
      scale and the risk of having a LBW infant.

PMID- 9643076
TI  - Flit-gun sprayer characteristics.
AB  - Six flit-gun sprayers were tested for possible use in mosquito adulticide
      programs where inexpensive nonmotorized application technology may be required.
      An analysis of variance for differences in droplets < or = 24 microns (mu),
      droplets > or = 48 mu, droplets/cm2, volume median diameters, and mosquito
      mortality is provided. As shown by these data, good results can be achieved with
      this equipment.

PMID- 9643080
TI  - [The Foundations of Bioethics by H. Tristram Engelhardt Jr.: comments on James F.
      Drane's review].

PMID- 9643081
TI  - Public health services: should they respond to demand or necessity?

PMID- 9643084
TI  - [Stress proteins: expression of a universal phenomenon of cell defense].
AB  - Heat shock proteins or stress proteins play a role in adaptative thermotolerance.
      All cells, procaryotic and eucaryotic, are able to respond to different cellular
      aggressions by the synthesis of these stress proteins. In normal physiological
      conditions, they are considered as "molecular chaperones" Their actual role in
      pathology is still unknown; some of these heat shock proteins may be correlated
      with the degree of aggressiveness of some tumors.

PMID- 9643085
TI  - [Re-evaluation of immunomodulator treatments for recurrent abortions].
AB  - Immunotherapy of spontaneous recurrent abortion is still a matter of controversy.
      Since 1985, 117 patients were treated in our center. Transfusions of paternal
      leucocytes (PL) were given to 56 patients and intravenous immunoglobulins
      (i.v.Ig) to 61 patients. The allocation of the two treatments was not randomised.
      Respectively 74% and 71% normal pregnancies were achieved. In two cases treated
      by paternal leucocytes, the appearance of anti-erythrocytes alloantibodies (anti
      c and anti Jkb + C) was noted. Two patients receiving i.v.Ig had a transient
      allergic reaction (urticaria). In the five patients presenting with spontaneous
      abortion in the setting of in vitro fecondation, four normal pregnancies were
      achieved. These encouraging results from a single center are still to be
      considered as preliminary but urge us on continuing this approach. One of the
      drawback of i.v.Ig is their cost. Use of paternal leucocytes constitutes an
      adequate alternative provided that a strict immunological selection of the father
      is performed to avoid lymphocyte or platelet alloimmunisation. Our results are
      discussed in the light of recent controlled studies emphasizing the importance of
      the placebo effect and in the light of the new concepts in pregnancy immunology
      (protective action of trophoblastic HLA-G and Th2 cytokines; antagonistic effect
      of endometrial NK cells.

PMID- 9643086
TI  - [Pneumococcal spondylodiscitis. A case report].
AB  - We report on a case of a 66 years-old patient suffering weight loss and lumbar
      pain, localized at L2-L3. A spondylodiscitis was revealed by CT and MRI;
      intervertebral disc puncture was positive for Pneumococcus Pneumoniae. The
      clinical evolution was good with the anti-bacterial treatment, while the patient
      developed a synostosis L2-L3. Incidence, bacteriology, imaging and therapy of
      spondylodicitis are discussed.

PMID- 9643087
TI  - [Anatomo-clinical conference: pulmonary cancer and cerebral vascular accident].
AB  - A patient with a lung adenocarcinoma died shortly after a first chemotherapy
      course from multifocal neurological lesions and severe cardiopathy. Autopsy has
      revealed the cause of these complications.

PMID- 9643088
TI  - [Transdermal fentanyl].
AB  - Fentanyl is a synthetic pure opioid agonist with a selective activity on mu
      receptors. Its high liposolubility allows a transdermal administration, using a
      Transdermal Therapeutic System (TTS). The clinical efficacy is widely
      demonstrated in the field of cancer pain control. The side effects are those
      observed with morphine but with less frequent constipation. The adjonction of a
      short acting morphine in case of acute pain is recommended.

PMID- 9643089
TI  - [Conductive deafness: anatomo-radiological correlation].

PMID- 9643090
TI  - [The problem of euthanasia legislation].

PMID- 9643091
TI  - [What is your diagnosis? Spontaneous pneumomediastinum (mediastinal emphysema)].

PMID- 9643092
TI  - [Dog, cat and human bites].
AB  - Animal and human bites carry a high risk of infectious complications. Human bites
      and in particular clenched-fist injuries as well as cat bites are highly prone to
      infection as are wounds that involve the hand or deep structures including
      joints, bones and tendons. The management of bite wounds consists of intensive
      irrigation with large volumes of normal saline and a cautions debridement of
      devitalized tissues. Generally, it appears prudent to leave the wounds open,
      however, in cases carrying a low risk of infection, a primary surgical closure
      might be appropriate. If a bite wound is infected, an antibiotic course with
      amoxycillin/clavulanic acid (first choice) or tetracyclines (second choice) for
      10-14 days is recommended. In patients who present early after the injury, an
      antibiotic prophylaxis for 3-5 days is appropriate, particularly when the risk
      for the development of infection is high. Furthermore, a tetanus booster and in
      case of possible transfer of rabies, a rabies vaccination with immunoglobulins
      and inactivated virus preparation is recommended.

PMID- 9643093
TI  - [Acute therapy of ischemic stroke].
AB  - Ischemic stroke is a neurological emergency as transition form reversible to
      irreversible lesions of the brain may be prevented by starting the therapy within
      six hours after the onset of the neurological deficits. Intravenous thrombolysis
      may be administered within the first three hours and intraarterial thrombolysis
      within the first six hours after considering inclusion and exclusion criteria.
      Neuroprotective drugs are under investigation and may enlarge the spectrum of
      acute therapy in the near future. Ischemic strokes that do not qualify for
      thrombolysis may be treated with unfractionated heparin, aspirin or low-molecular
      weight heparin. Indications for the administration of antithrombotic drugs are
      discussed. Blood pressure is frequently elevated in acute ischemic stroke, but
      rarely needs therapy or careful lowering. Fever, hypo- und hyperglycemia,
      epileptic seizures and intracranial hypertension should be treated.

PMID- 9643094
TI  - [Cool, clever, established--variations on anxiety defenses in today's society].
AB  - Anxiety is a psycho-biological phenomenon, psychologically manifested in feelings
      of constrainment, threat, and vulnerability; and physically in evidence of
      increased sympathetic tone. Three phenomenologically different forms of anxiety
      can be distinguished (real anxiety, existential anxiety, neurotic anxiety).
      Existential anxiety is based on four themes: self-development, self-submission,
      change and finality. Anxiety and anxiety defences are a part of human existence.
      Every culture develops its own rituals for defending against anxiety. Three
      variations of anxiety defence are described which typically appear in affluent
      societies: coolness, cleverness and happiness. These strategies are, depending on
      the situation, sensible and advantageous in dealing with, perceiving, overcoming
      and defending against existential anxieties.

PMID- 9643095
TI  - [Diagnosis and assessment of anxiety disorders].
AB  - Anxiety disorders tend to become chronic if untreated and often have considerable
      social consequences. Therefore, early recognition of anxiety disorders at the
      primary health care level is of great importance. This article gives a short
      overview of important aspects of the diagnosis of anxiety disorders in general
      medical practice. Panic disorder, generalised anxiety disorder and phobic
      disorders are describer and phobic disorders are described based on ICD-10
      criteria. Anxiety disorders have important differential diagnostic distinctions
      from somatic disorders and other psychiatric disorders. A diagnosis of panic
      disorder can be easily missed if physical symptoms are predominant. Also, there
      is a high comorbidity with depressive disorders, substance-abuse and -dependence
      and suicidality. Furthermore, during the assessment procedure the topics of
      psychosocial life situations, social effects and earlier treatments should be
      investigated.

PMID- 9643096
TI  - [Therapy of anxiety disorders in family practice].
AB  - A treatment algorithm for anxiety disorders in primary care practice is
      introduced. Anxiety is understood as a complex pattern which consists of
      thoughts, emotions, behaviour and physiologic reactions. Patient education is
      outlined as a crucial factor for the management of anxiety. Some examples of
      patient education are given. The most important pharmacological agents for the
      treatment of anxiety are benzodiazepines, antidepressants and buspirone. The drug
      treatment of some common anxiety disorders is presented. Finally the limits of
      anxiety management in primary care are discussed and some techniques of cognitive
      behaviour therapy are outlined.

PMID- 9643097
TI  - [Progressive decline in athletic performance].
AB  - A 48-year old engineer presented with progressive decline in sports performance.
      A history of latent hypothyroidism was known since 3 years. Adrenocortical
      insufficiency was suggested and confirmed by further investigations. Because of
      additional autoimmune thyroiditis and family history with autoimmune diabetes of
      the son, the diagnosis polyglandular autoimmune syndrome type II was made.

PMID- 9643098
TI  - [Subarachnoid hemorrhage in aneurysm of the left anterior cerebral artery].

PMID- 9643099
TI  - [Mild von type I von Willebrand disease].

PMID- 9643100
TI  - [The effect of the unilateral exclusion of nasal breathing on skull development
      in an experiment].
AB  - Unilateral disturbance of nasal respiration was modeled in albino rats. All
      animals developed deformations of the skull in the sagittal and transversal
      planes. The pathogenesis of deformations is connected with neurotrophic disorders
      and injury to the nasal cartilaginous structures responsible for the skull
      growth.

PMID- 9643102
TI  - [The microhardness of dental tissues as an index of their normal functional
      stability and in pathological states].
AB  - Microhardness of dental tissues was assessed. Hard tissue specimens from 65 teeth
      removed for medical indications were examined. The enamel microhardness is 30-40%
      decreased in caries, whereas dentine is virtually intact. Depulpation decreases
      the enamel microhardness by 23-26%, while the microhardness of dentine is changed
      negligibly (by 1-1.5%).

PMID- 9643101
TI  - [Clinico-laboratory studies of the properties of Aquafresh toothpaste].

PMID- 9643103
TI  - [A comparative analysis of the use of Uzor and Optodan laser apparatus for the
      prevention and combined treatment of pulpitis and periodontitis].
AB  - Clinical research 242 patients for comparison purposes of efficiently of
      employment of semiconductor laser apparatus "Uzor" and "Optodan" as
      physiotherapeutic of the factor for preventive maintenance and treatment of
      complications, arising the ambassador endodontic of treatment is spent. Results
      of application of semi-conductor laser apparatus are resulted at the various
      forms pulpitis and periodontitis. Significant reduction of a pain directly after
      a procedure LSL is marked. The highest efficiency is established by use of the
      apparatus "Optodan", connected with distinction configurations of a impulse.

PMID- 9643104
TI  - [A comparative evaluation of the efficacy of the conservative treatment of
      chronic apical periodontitis in patients with secondary immune deficiency and in
      somatically healthy persons].
AB  - The efficacy of conservative treatment of chronic apical periodontitis is
      compared is somatic patients and somatically healthy subjects. Twenty-seven
      patients with chronic obstructive bronchitis and secondary immune insufficiency
      and 31 patients without underlying diseases were treated. Conservative treatment
      of chronic apical periodontitis was insufficient in the patients with secondary
      immunodeficiency.

PMID- 9643105
TI  - [Cytological indices as criteria for assessing periodontal status].
AB  - The authors define the complex of criteria for analysis of cytograms of gingival
      impressions in health and periodontal diseases. Such criteria are needed for
      objective diagnosis and monitoring of periodontal status over the course of
      treatment. All the cellular elements were taken account of: different types of
      epithelial cells, including those with signs of cytopathology and bacterial
      contamination, connective tissue cells, mononuclears, leukocytes, and
      fibroblasts. The cytological picture correlated with the status of periodontium
      and forms and severity of pathological processes developing in it.

PMID- 9643106
TI  - [The comparative efficacy of nonsteroidal anti-inflammatory agents in the
      combined treatment of periodontal diseases].
AB  - Nonsteroid anti-inflammatory drugs (NAID) are compared in 120 patients with
      periodontitis. The results confirmed clinical efficacy of modern NAID in this
      patient population. The best clinical results were achieved with voltaren. Local
      anti-inflammatory efficacy of dressings with acetylsalicylic and orthophene
      ointments and pyroxiphene was virtually the same.

PMID- 9643107
TI  - [The effect of different concentrations of dimexide and ortofen on the T-cell and
      neutrophil components of immunity].
AB  - Clinical and immunological efficacy of 2.5% orthophene and 50% dimexide used to
      arrest an acute inflammatory process in the periodontium is assessed. Three types
      of salivary neutrophils are distinguished, similar to previously detected types
      of response of blood immunocompetent cells. Both drugs had a favorable impact on
      the functional activity of blood T-lymphocytes, blood and salivary neutrophils
      and are recommended for patients with types I and II reactions of immunocompetent
      cells of the blood.

PMID- 9643108
TI  - [The immune and dental status of women who have given birth to infants with
      intrauterine growth retardation].
AB  - Secondary immunodeficiency was detected in women who gave birth to small-for-date
      newborns. This state was one of the causes of periodontal and hard dental tissue
      involvement. Women with small-for-date fetuses are at risk of dental diseases.

PMID- 9643109
TI  - [The clinico-morphological basis for the combined treatment of lichen ruber
      planus of the oral mucosa using Solcoseryl].

PMID- 9643110
TI  - [A method for the surgical treatment of pericoronitis using a computerized laser
      apparatus].
AB  - Use of pulsed exposure to CO2 laser permits operations on soft tissues of the
      oral cavity with the minimal injury. The choice of optimal parameters of laser
      exposure depends on the stage of the inflammatory process. The proposed ablation
      regimen for the treatment of pericoronitis notably accelerates the treatment and
      decreases the amount of drugs used. The absence of complications after the
      operation and a shorter rehabilitation period recommend the Lancet computer-aided
      laser for dissection of the veil.

PMID- 9643111
TI  - [A comparative evaluation of the efficacy of the isolated and joint use of
      dioksizol and low-frequency ultrasound in the combined treatment of phlegmons of
      the maxillofacial area].
AB  - The effects of dioxycol and low-frequency ultrasound alone and in combinations on
      the microflora of suppurative wounds formed after opening of maxillofacial
      phlegmons are assessed in 142 patients. Clinical and laboratory findings indicate
      a higher efficacy of combined use of these treatment modalities, which are
      recommended for optimal local treatment of purulent maxillofacial wounds.

PMID- 9643112
TI  - [The new potentials for reconstructive restoration in defects of the lower lip
      after cancer operations].
AB  - Eleven patients with cancer of the lower lip were treated in 1995-1996. The first
      stage of treatment consisted of radiotherapy, the second one of resection of the
      lower lip with replacement of the defects with a dermatocutaneomucous flap from
      the cheek, including all anatomical components and hence permitting anatomically
      full-value repair of the lower lip. The method is reliable and effective.

PMID- 9643113
TI  - [The disinfection of impressions to prevent hospital infections. Sodium
      hypochlorite as a disinfecting agent].
AB  - Effect of sodium hypochlorite disinfection of impressions on the size and quality
      of plaster models is studied. Twenty-minute submerging of silicone impressions in
      0.5% sodium hypochlorite solution did not change their size and did not
      deteriorate the quality of surface and hardness of plaster models. Stomalgin
      impressions cannot be disinfected by sodium hypochlorite solution because of
      expressed destructive effect of this disinfectant on the impressions.

PMID- 9643114
TI  - [The characteristics of the muscular activity of the maxillofacial area in
      persons with partial tooth loss depending on the extent of the dentition defect].
AB  - The electromyogram (EMG) amplitude of the masticatory and temporal muscles is
      decreased and EMG amplitude of suprasublingual muscles increased during
      mastication or voluntary occlusion in patients with class I dentition defects in
      comparison with the controls. The changes were the greater, the more antagonist
      pairs were missing. The duration of masticatory period and the number of
      masticatory movements increased. The most notable changes in the muscular
      activity are observed in subjects with 4 antagonist pairs missing.

PMID- 9643115
TI  - [The clinical manifestations of the electrochemical processes due to the
      finishing treatment of dentures made from stainless steel].
AB  - The authors propose to treat stainless steel dentures by grinding on
      organosilicon binding followed by 2 polishing procedures: with diamond paste and
      paste based on ultradispersed aluminum oxide powder. This technology improves the
      corrosion resistance of dentures and eliminates signs of diseases caused by
      electrochemical processes in the oral cavity more effectively than basic
      technology (vulcanite grinding and polishing with GOI paste).

PMID- 9643116
TI  - [Occlusal anomalies in the deciduous and mixed bites].
AB  - In 311 examinees (177 boys and 134 girls) with primary dentition and 535
      examinees (285 boys and 250 girls) with mixed dentition in Istria--Croatia, the
      frequency of orthodontic and occlusal anomalies in regard of space plane and
      premature extraction of c, m1 and m2 are investigated. The orthodontic anomalies
      are fortified in 46.95%, premature loss in 11.25% and occlusal anomalies in
      40.83% of examinees with primary dentition, while in mixed dentition the 58.69%
      of examinees have orthodontic anomaly, the 17.20% premature loss and the 48.97%
      of examinees have occlusal anomaly. In both phases of dentition the most frequent
      are occlusal anomalies: combination of sagittal-vertical plane, and those in
      sagittal and vertical space plane respectively.

PMID- 9643117
TI  - [The use of the Optodan laser physiotherapeutic apparatus for the prevention of
      complications and the acceleration of the time in treating anomalies in the
      position of individual teeth with fixed orthodontic appliances].
AB  - Physiotherapy including laser exposure was used in the treatment of 243 patients
      aged 13-34 years with abnormal occlusion. The results indicate that laser
      exposure effectively relieved pain after fixation and activation of permanent
      orthodontic devices, treated gingivitis before and during orthodontic treatment,
      prevented exacerbations of periodontitis, and accelerated eruption of retained
      teeth.

PMID- 9643118
TI  - [An automated computer system for the differential diagnosis and laser treatment
      of benign neoplasms and tumor-like masses in the oral cavity].
AB  - Automated computer system for differential diagnosis and defining the indications
      for pathogenetic therapy is described, which was used in 2816 patients and was
      effective in 97% of cases. The system includes computer-regulated Lancet surgical
      lasers (wavelength 10.6 microns, power 60 W, frequency 0.05-1.0 Hz) and Optodan
      physiotherapeutic laser (wavelength 0.85 micron, power 4 W, frequency 0.08-3
      kHz).

PMID- 9643119
TI  - [A computerized expert system for the diagnosis and prognosis of the course of
      acute odontogenic inflammatory diseases (DIAPRO)].
AB  - A computer-aided expert system for diagnosis and prediction of the course of
      acute odontogenic inflammatory diseases DIAPRO is created. Based on commonly used
      laboratory and clinical parameters, it permits a long-distance diagnosis of acute
      maxillofacial inflammations and their complications and provides data for 13
      signs of patient's status.

PMID- 9643120
TI  - [The morphological pathology of the "double lip" (a clinical case)].
AB  - Morphological changes of tissues in patients with macrocheilia or so-called
      "double lip" are described. These changes refer this abnormality to teratomas.
      Surgical treatment of the condition is discuss.

PMID- 9643121
TI  - [Experience in organizing an office for functional diagnosis based in an urban
      dental polyclinic].

PMID- 9643122
TI  - Shaken baby syndrome.

PMID- 9643123
TI  - [HIV epidemic].

PMID- 9643124
TI  - [HIV diagnosis 1998].
AB  - Due to considerable technical progress during the last few years the diagnosis of
      HIV-infection has been substantially improved. Third generation antibody
      screening assays, which also detect antibodies of the IgM and IgA type, have
      considerably narrowed the immunological window. The determination of the viral
      load in peripheral blood employing nucleic acid amplification techniques is now
      generally available and used for diagnostic and prognostic purposes as well as
      for the monitoring of antiviral therapy. To detect a HIV-infection the antibody
      screening assay is primarily used and complemented by the HIV-1 p24 antigen assay
      provided an early primary infection is suspected. In the latter case the antibody
      screening assay is often negative or indeterminate, while the p24 antigen assay
      is positive. According to the 1998 guidelines of the Federal Office for Public
      Health, the physician will be informed of the screening assay result without the
      need to await a confirmatory test in case of a reactive screening assay in the
      first sample. Confirmation, e.g. by immunoblot, will be done in a second blood
      sample which should be sent to the laboratory as soon as possible. EDTA-blood is
      recommended for this purpose, because it is best suited for quantification of
      plasma viremia, which has become a prerequisite for the institution and follow-up
      of antiretroviral treatment. The second sample will also serve to exclude false
      positive results due to clerical errors, and to determine the type of HIV, i.e.
      HIV-1 or HIV-2. The concept outlined should accelerate the availability of
      reactive test results to the physician and should reduce the cost of the
      diagnostic procedure.

PMID- 9643125
TI  - [Sexual transmission of HIV: effect of potent antiretroviral therapy].
AB  - The recent progress of our understanding of the pathophysiology of human
      immunodeficiency virus (HIV) infection and the availability of new antiretroviral
      compounds has markedly improved the prognosis of patients infected with HIV. It
      has been postulated as early as 1991 that potent community-wide treatment of HIV
      infection could paradoxically lead to an increased spread of the HIV epidemic if
      treatment is not associated with a reduced infectivity of HIV. In the past few
      years, several groups have demonstrated a good correlation of the quantity of HIV
      present in semen with factors that are known to increase the likelihood of sexual
      transmission of HIV. A similar correlation has recently been demonstrated for the
      presence of HIV in female genital secretions. During the past year, a number of
      studies have demonstrated a marked effect of antiretroviral treatment on the
      shedding of HIV in the male and female genital tract, indicating a potential role
      of antiretroviral treatment for the prevention of HIV infection. Although potent
      antiretroviral therapy is beneficial on a public health basis, patients with no
      detectable virus in their blood or semen under treatment should not be considered
      non-infectious and patients should keep up with safer sex practices.

PMID- 9643126
TI  - [Post-exposure HIV prevention within and outside the hospital].
AB  - There is a low risk of infection with the human immunodeficiency virus (HIV) for
      HCW through exposure in the work place. The mean risk of infection with HIV after
      a percutaneous exposure is 0.3%. This risk can be considerably higher depending
      on various factors: for example, a deep percutaneous injury or the source patient
      being in an end stage of HIV infection. Despite compliance with adequate
      precautions, it is not always possible for HCW to avoid injuries. This fact has
      made intervention desirable after such exposure. Zidovudine (AZT) was available
      as the first effective drug for treatment of HIV infection. Also, animal
      experiments have shown efficacy in prophylactic use of zidovudine. Therefore,
      since the beginning of the 90's, there has been an increased use of postexposure
      prophylaxis with zidovudine for exposed HCW, and during this period of use more
      evidence has come up to show the efficacy of PEP. In fact, a large retrospective
      case-control study showed a 81% reduction of HIV transmission to exposed HCW in
      the zidovudine treated group after percutaneous exposure. Based upon this
      impressive evidence and other data which indicate the efficacy of PEP,
      postexposure prophylaxis has become a standard procedure in the health care
      setting after a significant exposure to HIV. A combination of three
      antiretroviral drugs, usually including a protease inhibitor, is used today.
      Based on our current pathogenetic understanding, PEP should be started as soon as
      possible after exposure to HIV. There are effective tools for preventing HIV
      transmission in the general population. However, these tools do not provide
      universal protection: rupture of condoms, needle sharing and unprotected
      intercourse with a HIV infected person are situations at risk of HIV
      transmission. In spite of a different mode of exposure when compared to the
      health care setting, PEP in timely application is believed to be efficacious. To
      date there is no controlled data to support PEP in such situations; however, PEP
      with a combination of antiretroviral drugs after anal, oral (with ejaculation) or
      vaginal intercourse and needle sharing with a HIV-positive partner is recommended
      for a minimum of two weeks. There are reservations in recommending PEP after
      unprotected sexual intercourse with a partner of unknown serostatus.

PMID- 9643127
TI  - [Emergencies in HIV infection].
AB  - Emergencies in HIV-infected patients are a common complication which may occur at
      any stage of the disease. Opportunistic infections may lead to irreversible
      damages of organs such as the brain, the eye or the lung. With the widely use of
      antiretroviral therapy side effects of reverse transcriptease inhibitors and
      proteinase inhibitors and drug interactions are frequent causes of severe
      symptoms such as nausea and diarrhoea or of complications such as anaemia or
      leucopenia. As with Non-HIV-associated emergencies empiric therapy may be
      necessary to treat patients to prevent severe organ damage.

PMID- 9643128
TI  - [Prevention of opportunistic infections in HIV-infected adults].
AB  - Opportunistic infections have a major influence on morbidity and mortality in HIV
      infected individuals. Prophylactic measures have to be introduced for each
      patient, corresponding to the stage of disease measured by CD4-lymphocyte count.
      They consist of exposure prophylaxis, vaccinations and especially
      chemoprophylaxis with antimicrobials. Some live vaccines are contraindicated in
      HIV infected patients. Pneumococcal vaccine for every patient and specific
      primary prophylaxis against pneumocystis carinii pneumonitis, cerebral
      toxoplasmosis and M. avium infection in patients with manifest immunodeficiency
      improve survival and quality of life of many patients. After most opportunistic
      infections, secondary lifelong antimicrobial prophylaxis is indicated. In future,
      indications of primary and secondary prophylaxis have to be redefined in the
      light of the new antiretroviral combination therapies.

PMID- 9643129
TI  - [Clinically significant drug interactions in HIV-infected patients].
AB  - In recent years the availability of highly active antiretroviral therapies and
      prophylaxis and treatment of opportunistic infections in patients with HIV
      disease have reduced morbidity and mortality. Many different drugs may be
      prescribed in a patient simultaneously. Therefore, the potential for interactions
      between different substances is increased. The possible mechanisms of drug
      interaction concern pharmakokinetics (absorption, metabolism, elimination) and
      pharmakodynamics. They can lead to significant changes in plasma concentrations
      and may affect efficacy and toxicity of a drug. One of the most important
      mechanisms of interaction is the inhibition or induction of the hepatic
      cytochrome P-450 enzyme system. All protease-inhibitors are metabolized by
      CYP450, mostly by the subunit 3A4. Proteinase-inhibitors are themselves very
      potent inhibitors of CYP4503A4 and increase the concentration of drugs
      metabolized this way. This article summarises the most important mechanisms of
      drug interactions and demonstrates the most frequent and clinical significant
      consequences.

PMID- 9643130
TI  - [Decision guides for antiretroviral treatment in pregnancy].
AB  - HIV-infected adults can now be offered highly active antiretroviral combination
      therapies. Major advances in understanding the pathogenesis of HIV-infection have
      led to earlier onset of treatment during the course of HIV infection. Most of the
      new antiretroviral drugs are not approved for use in newborns and infants.
      Zidovudine monotherapy during pregnancy, during labor and for the newborn, has
      been shown to reduce vertical HIV transmission by almost 70%. Zidovudine
      monotherapy is at present considered obsolete for the treatment of HIV-infected
      adults. Thus, during pregnancy, both the interests of the HIV-infected mother and
      the fetus/newborn must be taken into account. Clinical data to solve this dilemma
      are not available. In general, standard antiretroviral treatment should not be
      withheld from pregnant HIV-infected women, but prescription has to be the result
      of careful discussion of the risks and benefits of such treatment during
      pregnancy. The final decision about treatment, whether primarily for the mother,
      to reduce vertical transmission or both, has to be taken by the pregnant women.
      This discussion and information must involve physicians with important experience
      in the treatment of HIV-infected patients.

PMID- 9643131
TI  - [The Swiss HIV Cohort Study--a link between clinical research and medical
      practice].
AB  - The prospective Swiss HIV Cohort Study (SHCS) documents since 1988
      epidemiological, clinical and laboratory data of HIV-infected participants. Until
      the end of 1997, 9447 patients with a total follow-up of 25,584 patient-years
      have been included. The proportion of women is 27.3% and is rising. The
      proportion of heterosexually infected patients has been rising since 1992, this
      group was with 35.6% in 1997 the most frequent transmission category within the
      newly registered participants. The SHCS is representative for Switzerland since
      73% of the 5532 nationwide registered AIDS cases are included in the study.
      Recently, the SHCS data could demonstrate an impressive reduction in morbidity
      and mortality due to the improvement in therapy and prophylaxis. The SHCS also
      serves as a basis for large multicenter studies that aim to evaluate new
      prophylactic treatments or new antiretroviral strategies. By introducing uniform
      guidelines for the diagnosis and the treatment of HIV infection, the SHCS has
      contributed significantly to the high quality of patient care, a goal that must
      be maintained and further improved in the future. Also important is the
      recognition of acute HIV infections because early treatment of such patients
      holds the promise to substantially improve the clinical course.

PMID- 9643132
TI  - [Stress echocardiography--principles, methodology, results and indications].

PMID- 9643133
TI  - [Means for optimizing the parameters of physiotherapeutic exposures].
AB  - The paper deals with the problem of adequacy of electromagnetic exposure of
      biological systems, indicates principal directions of optimization of
      physiotherapeutic actions including necessary hard and software, methodology of
      registration of the body response to these effects.

PMID- 9643134
TI  - [The comparative clinico-physiological characteristics of the action of air
      carbon dioxide-radon baths in patients with ischemic heart disease].

PMID- 9643135
TI  - [Transcerebral exposure to sinusoidal modulated currents in bronchial asthma
      patients].
AB  - Clinical examination of 85 patients with bronchial asthma (BA) revealed thyroid
      affection proved by ultrasonic and/or hormone profile investigation in 42(49%)
      patients. Transcerebral treatment with sinusoidal modulated currents gave rise to
      positive trends in external respiration, clinical and biochemical blood indices,
      immunity status which appeared more pronounced in BA patients without the
      endocrine disorder.

PMID- 9643136
TI  - [The use of an aerosol of natural brine and of sinusoidal modulated currents in
      chronic pneumonias in children].
AB  - Inhalations of 1% natural brine in combination with SMC electrophoresis of 1%
      natural brine above the lesion proved to ensure good correction of the defense of
      respiratory tract mucosa and to prolong remission to 15-18 months. This method
      can be applied in sanatoria, in rehabilitation centers, in pulmonary disease
      departments.

PMID- 9643137
TI  - [The pelotherapy of patients with periodontitis].
AB  - 90 patients with periodontitis have received peloid therapy. Mineral mud from
      Lake Goreloye deposits was applied by means of a specially developed device
      providing good contact of the mud with the gingiva and teeth. A good clinical
      response was achieved.

PMID- 9643138
TI  - [The use of laser puncture in the combined treatment of peptic ulcer patients].

PMID- 9643139
TI  - [The treatment of patients with chronic intestinal diseases at a balneological
      sanatorium].

PMID- 9643140
TI  - [The comparative effect of classic massage of different intensities on patients
      with chronic salpingo-oophoritis].
AB  - Massotherapy in different regimens has been used in 30 patients in remission of
      chronic salpingo-oophoritis (CSO). The massage produced positive changes in blood
      coagulation, immune status, regional hemodynamics of the small pelvis,
      bioelectric activity of the muscles of the anterior abdominal wall and
      lumbosacral region. A strong anesthetic and antiinflammatory effect of intensive
      massage in 78%, recovered reproductive function in 33% of the patients allow to
      recommend intensive massage as possible monotherapy of patients in remission of
      CSO.

PMID- 9643141
TI  - [The sequential use of cryotherapy and the electrophoresis of nicotinic acid by
      sinusoidal modulated currents in the treatment of patients with osteochondrosis
      of the cervical spine].

PMID- 9643142
TI  - [The types of traction in osteochondrosis of the lumbar spine].
AB  - The effects of low-intensive tractions were evaluated clinically and
      electrophysiologically in 148 patients with neurological symptoms of lumbar
      osteochondrosis. The above tractions were combined with vibration, peloid
      electrophoresis and sulphide baths. Indications and contraindications for
      tractions are outlined. The above complexes are recommended for use in the
      programs of rehabilitation of patients with osteochondrosis of the lumbar spine.

PMID- 9643143
TI  - [The use of cardiointervalography for assessing the tolerance for intensified
      courses of physiobalneotherapy in patients with osteoarthritis].

PMID- 9643144
TI  - [The use of transcutaneous electrostimulation in the treatment of diabetic
      angioneuropathy].
AB  - Transcutaneous electrostimulation (Amplipul's-4 unit) was used in 29 patients
      with diabetes mellitus and diabetic angioneuropathy. The impact was directed to
      three fields a session: paravertebral, musculus gastrocnemius, feet.
      Rheographically, a good clinical response with improvement of peripheral
      circulation was achieved.

PMID- 9643145
TI  - [Bioelectrostimulation in the rehabilitation of patients with gunshot wounds of
      the peripheral nervous system (a clinico-immunological study)].
AB  - Immune homeostasis was studied in 35 patients with gunshot injuries of the
      peripheral nerves in the process of rehabilitation using bioelectrostimulation of
      the muscles impaired. Parameters of cellular and humoral immunity were
      determined. Bioelectrostimulation resulted in the regression of preexisting
      motor, sensitive, vegetovascular and trophic disorders. Cellular and humoral
      immunity improved: the number of T-lymphocytes, T-helpers, T-suppressors
      increased, the immunoregulatory index normalized, levels of B-lymphocytes,
      immunoglobulins G, circulating immune complexes reduced. Thus,
      bioelectrostimulation in patients with gunshot injuries of the peripheral nerves
      corrects the disturbed homeostasis and promotes recovery of the functions lost.

PMID- 9643147
TI  - [A comparative evaluation of the effect of different types of sapropel on dynamic
      liver function in intact rats and in the modelling of toxic hepatitis].
AB  - A course of silicic sapropel applications compared to calcareous sapropel induced
      a reversible fall of total lipid concentration in blood serum of intact rats.
      Sapropels of different kinds and of the same kind but obtained from different
      depths of the same deposit varied by their ability to correct hepatic function in
      rats with toxic hepatitis. The highest benefit was registered in application of
      carbonate sapropels taken from the depth of 1.5-2.5 m.

PMID- 9643146
TI  - [The effect of the combined action of applications of sapropel and of a
      nonuniform permanent magnetic field on the dynamics of the recovery processes in
      damage to the liver parenchyma (experimental research)].
AB  - Effectiveness of applications of saprol and nonuniform constant magnetic field
      (NUCMF) used alone and in combination was studied on the model of experimental
      toxic rat hepatitis. NUCMF had no advantages over saprol in correction of hepatic
      tissue function. However, combination of these two modalities was more effective
      than each of them. Possible mechanisms of such effect are discussed.

PMID- 9643148
TI  - [The information value of the cardiorespiratory system indices of rats in
      assessing the dependence between heat inflow from peloid application and the
      body's reaction].
AB  - Informative value of cardiorespiratory parameters of rats in respect to dose
      effect effectiveness was studied in relation to thermal action of therapeutic
      peloid. Systolic blood pressure and respiratory rate are highly informative
      whereas heart rate is not responsive to thermal effect of the peloid. Possible
      explanation of the above facts are discussed.

PMID- 9643149
TI  - [The marketing characteristics of sanatorium-health resort institutions].

PMID- 9643150
TI  - [The organization of a medical rehabilitation service].

PMID- 9643151
TI  - [The problems of radon therapy: its benefits and risks].

PMID- 9643152
TI  - Human resources development for the prevention of blindness in Anglophone West
      Africa.
AB  - As recent as 1986, acute shortage of qualified manpower was one of the major
      difficulties in the prevention of blindness in Africa. Following the WHO sub
      regional workshop on Manpower development for Prevention of Blindness, the West
      African Health Community in collaboration with the National Prevention of
      Blindness programmes in Anglophone West Africa made concerted efforts at
      developing appropriate manpower at all levels of eye care. Eight categories of
      eye care workers were identified and personnel to population ratios adopted for
      each. Curriculum was developed and training begun for two new cadres-Primary Eye
      care Trainers and Diplomate Ophthalmologist. These are expected to boost the
      training of Integrated Eye Care workers for primary eye care and increase
      surgical services, especially cataract surgery rates, at secondary eye care level
      respectively. There are constraints and difficulties but the support provided by
      two non-government organisations (Sight Savers International and Christoffel
      Blindenmission) had been helpful in overcoming some of these. Significant
      progress has been made in the last decade in developing the required manpower but
      large deficits still remain. The political will, commitment and co-operation of
      all stakeholders would be required to achieve the desired targets for the next
      decade.

PMID- 9643153
TI  - [Treatment of early T1 small T2N breast cancers. Our experience at the Yaounde
      General Hospital. 21 cases].
AB  - From February 1989 through February 1993, a group of 23 patients suffering from
      T1 mammary carcinoma small T2 N-MO was treated in the radiotherapy department of
      the Yaounde General Hospital, according to a simplified procedure. A first
      conservative surgery of tumorectomy type (3 cases) and quandrantectomy type (4
      cases) was carried out, followed by a postoperative irradiation. In 14 cases, a
      Patey type radical surgery preceded a local/regional radiotherapy. The general
      treatment was made up of only a hormonotherapy without chemotherapy. After a 4
      year decline, there were 5 cases--i.e. 23.8%--of ganglionic and/or metastatic
      relapse. In the light of research data, we are analysing the reasons for these
      unexpected therapeutic failures in this group of tumor considered as favorable
      prognosis. We raised the problem of the inability of the prognosis factors,
      presently defined by means of histological and biological factors, to detect all
      the especially aggressive cancers. We carried out a general review of the new
      factors defined essentially from molecular and genic bases. We offered an
      approximative solution which makes it possible to by-pass the technological
      difficulties in having access to the new factors.

PMID- 9643154
TI  - Febrile illness a major cause of profound childhood deafness in Nigeria.
AB  - A prospective study of 63 children with profound deafness seen personally at the
      E.N.T. Clinic, University of Nigeria Teaching Hospital, Enugu between January,
      1984 and October, 1987 is the subject of this paper. There were 35 males and 28
      females. Thirty-six (57.1%) were in the age group, 0-3 years, 17 (27%) in the age
      group 4-6 years, 7 (11.1%) in the age group 7-10, and 3 (4.8%) over 11 years.
      Febrile illness 41.3% was the most common cause followed by unknown with about
      20.6%. The various causes were compared with causes from other parts of the
      world. The possible causes of the febrile illness with special emphasis on the
      role of viral infections and malaria are highlighted. Mention is made of possible
      preventive measures.

PMID- 9643155
TI  - Screening of potential semen donors for sexual transmitted diseases.
AB  - BACKGROUND AND OBJECTIVES: The risk of infection with sexually transmitted
      diseases (STDs) is of great concern to couples undergoing therapeutic donor
      insemination. GOAL OF STUDY: We sought to determine the prevalence of STDs in
      potential semen donors and assess the rate of acquisition of new infection during
      the follow-up period. STUDY DESIGN: 29 potential semen donors were screened for
      common STDs. RESULTS: The study population had a prevalence of the following
      STDs: 27.5% ureaplasma, 13.8% mycoplasma, 6.9% cytomegalovirus 6.9% group B
      streptococcus, and 3.4% human papillomavirus infection. No participant tested
      positive for gonoccoccal or HIV infection. Over all, evidence of STD was present
      in 10 of 29 (34.5%) prospective donors. A follow-up infection rate of 22.2% (6 of
      27 enrolled donors) was found and 3 (11.1%) of these were excluded from semen
      donation. CONCLUSION: A high prevalence of sexually transmissible infections is
      present in potential semen donors. New infections are also common during the
      follow-up period.

PMID- 9643156
TI  - Trends in cervical cancer screening in Ibadan, Nigeria: a four-year review.
AB  - A four year retrospective review of cervical cytology services at the University
      College Hospital between 1992 and 1995 was carried out with a view to evaluating
      the trends in attendance, cost, sociodemographic characteristics and pattern of
      abnormal smears. The results were compared to those of an initial 4-year period
      (1988-1991) when the service was initiated. Fifty-three percent (53.8%) of 1,127
      smears taken during the period were routine smears. Majority (45.8%) of the
      smears were non-specific inflammatory changes while 26.8% were negative. Cervical
      intraepithelial Neoplasia (CIN) was diagnosed in 11.8% while 5 patients (0.44%)
      had neoplastic changes. The mean age were 39.8 (+/- 9.5), 40 (+/- 9), 52 (+/- 6)
      years for the entire study population, patients with CIN and patients with
      neoplastic changes respectively. There is a general decline in the number of
      smears taken while the cost of the procedure increased over the study period. In
      10.5% there are inadequate documentation and missing results. In our country
      where cervical cancer is the commonest female malignancy and leading cause of
      death among women, there is an urgent need to reverse this unfavourable trend,
      through use of public education, inducement, staff motivation and training in
      addition to computerisation of data.

PMID- 9643157
TI  - Utilisation differentials in a rural Nigerian health centre.
AB  - The Ala-Idowa health centre was established in 1980 to serve the two contiguous
      communities of Ala and Idowa with population of 3960 and 6580 respectively.
      Situated reasonably between the two communities, there is adequate physical
      accessibility to the health centre from both sides. The population structure of
      the combined community was determined through a household survey involving 125
      households selected systematically from the total of 2500 households. A
      comparison is presented between this structure and that of the population of
      attendees at the outpatient department of the Ala/Idowa health centre as recorded
      in the outpatient register with a view to discerning differentials in utilisation
      among different age groups. The data showed that those under the age of 15 years
      made more use of the health centre services than any other age group. Also, of
      the total of 958 patients for whom a diagnosis was recorded, 565 (56%) presented
      with an infection or infestation alone while another 4% presented with an
      infection together with another condition. Malaria accounted for 358 (63.4%) of
      all reported cases of infection/infestation. It is hoped that the findings of
      this study can be used to further target health centre services at the
      appropriate groups within the community as well as directed to those conditions,
      particularly communicable and preventable, that continue to exert great morbidity
      on the populations of developing communities.

PMID- 9643158
TI  - Seroprevalence of hepatitis markers; HAV, HBV, HCV and HEV amongst primary school
      children in Freetown, Sierra Leone.
AB  - The prevalence of hepatitis markers (Hepatitis A, B, C and E) in primary school
      children in Freetown, Sierra Leone was investigated in a government school,
      representative of the urban middle class. The children were aged between 6-12
      years old. A sub-sample (n = 120) of the 450 pupils were invited to participate.
      Of the 66 volunteers (mean 8.32 years) 12 were positive for HBsAg (males 9,
      females 3) and 11 were confirmed. Six of these were HBeAg positive, anti-HBe
      negative, (male 5, female 1). Whilst 6 were HBeAg negative, anti-HBe positive
      (male 4, female 2). HBcAb was present in 47 children (71%). Hepatitis A, C and E
      antibodies were detected in 64 (97%), 1 (2%) and 5 (8%) of children respectively.

PMID- 9643159
TI  - Evaluating the laboratory techniques used in the diagnosis of sputum-producing
      patients suspected of Mycobacterium infection.
AB  - Because of the susceptibility of HIV-infected persons to Mycobacterial
      infections, more sensitive diagnostic technique are being employed to detect
      Mycobacterium spp from clinical specimens. This study was therefore carried out
      to evaluate the sensitivity of methods used for the diagnosis of mycobacterial
      infections among sputum producing patients. Sputum samples from 160 patients were
      examined for Mycobacterium spp using direct smear microscopy, concentrated smear
      microscopy, and cultural method. The cultural technique detected the highest
      number of positives, 62 (38.8%), followed by concentrated smear technique,, 41
      (25.6%) while direct smear technique detected only 24 (15.0%). The results show
      that cultural technique should be employed for the diagnosis of Mycobacterium in
      order to avoid false negative results. However, concentrated smear technique
      should always be carried out, so that treatment could commence immediately in
      obviously positive cases.

PMID- 9643160
TI  - The effect of lacidipine on patients with mild to moderate hypertension and the
      effect of a combination of lacidipine and hydrochlorothiazide in the treatment of
      hypertension uncontrolled after four weeks of lacidipine treatment: an open
      study.
AB  - In the treatment of hypertension, some patients may go off control while still on
      the drugs. This occurs especially with sympathetic inhibitors and vasodilators.
      Lacidipine, a new calcium antagonist acts principally by vasodilatation. After a
      wash out period, patients with mild to moderate hypertension received 4 mg of
      Lacidipine for two weeks. After evaluation at two weeks, those uncontrolled
      received 6 mg of Lacidipine, while those controlled continued with 4 mg of
      Lacidipine for another two weeks. By the next evaluation, while patients
      continued whatever doses they were on, any one who had gone off control had 25 mg
      of Hydrochlorothiazide added. They were evaluated finally after another two
      weeks. It was found in this study that 91.3% (21/23) were controlled by the end
      with only Lacidipine either in 4 mg or 6 mg doses. Another 8.7% (2/23) initially
      controlled on Lacidipine went off control while still on the drug, and were
      eventually controlled by adding Hydrochlorothiazide. Some transient side effects
      not warranting discontinuation were encountered. It is concluded that Lacidipine
      is effective as monotherapy in mildly to moderately hypertensive Nigerian
      Africans; with good tolerance and safety profile. Where transient control is
      encountered, addition of a diuretic could be beneficial.

PMID- 9643161
TI  - Lysis of left ventricular thrombus with urokinase in a patient with alcohol heart
      disease.
AB  - A dilated cardiomyopathy patient whose congestive cardiac failure was made
      refractory to treatment by a left ventricular thrombus is reported.
      Thrombolectomy is usually the preferred therapeutic approach over anticoagulation
      and thrombolysis, as the latter approaches are said to carry the risk of stroke
      and haermorrhage. Facilities for thrombolectomy may not be available or
      affordable in our setting, and in some patients not practicable. Where 2-D echo
      facilities are available to indicate complete lysis, thrombolysis may be a way
      out.

PMID- 9643162
TI  - Atrial myxoma--a case report and review of the literature.
AB  - Myxomas are the most common primary cardiac tumours. They are usually benign and
      have variable presentation. Although rare, atrial myxomas are the most important
      cardiac tumours to diagnose, as they have an excellent prognosis following
      surgical excision. We report a 56 year old man who presented with features of
      both right and left heart failure. Ausculation of the heart revealed an apical
      mid diastolic murmur. Two-dimensional colour flow Doppler echocardiography
      revealed a pedunculated left atrial myxoma that prolapsed into the mitral valve
      orifice in diastole producing functional mitral valve stenosis. The patient
      underwent a successful surgical excision of the tumour. The diagnosis and
      management of atrial myxomas is reviewed.

PMID- 9643163
TI  - An unusual chest impalement.
AB  - We present the case of a 49-year old farmer, a combatant in communal clash over a
      piece of farmland on the Jos Plateau, who was impaled on his chest by a 13.5 cm
      long metal arrow, 56 hours prior to presentation. The arrow hit him tangentially
      on the left side of the chest and disappeared completely into his chest
      traversing the chest wall and lacerating the superior lingula segment of the lung
      but the tip of the arrow was only about 1.5 cm short of the pericardium. We are
      not aware of any report in literature on a patient in the West African sub-region
      who sustained and survived such serious chest impalement by a rigid object for
      more than two days before hospitalisation. Sustained public education and
      enforced legislature against the use of such lethal weapons will go a long way in
      preventing serious injuries of this nature.

PMID- 9643164
TI  - Correlation of mATPase, parvalbumin, and cytochrome c oxidase in rat skeletal
      muscle fibres.
AB  - Muscle fibre typing is conventionally performed on unfixed frozen sections.
      Within the particular classes of fibre types mATPase correlates well with the
      type of myosin heavy chain (MHC). However, investigation of other properties,
      e.g., parvalbumin (PV) level, cannot be determined on unfixed frozen sections.
      Determination of PV, which correlates with the relaxation time, is performed
      immunohistochemically on fixed tissue. By that method a comparison of mATPase
      activity and the amount of PV within the same muscle fibre is difficult. The
      present method, combining histochemistry of mATPase and cytochrome c oxidase with
      parvalbumin immunohistochemistry on consecutive sections, allows the distinction
      of six fibre types: I, IB, IIA, IIB, IIAB, IIX, and a C fibre population without
      division into IC and IIC fibres. The advantages and disadvantages of the present
      method are discussed.

PMID- 9643165
TI  - Composition of lipids from the glands of the external ear canal of the adult
      chicken.
AB  - Six classes of neutral lipids, i.e. triacylglycerol (TG), free fatty acids (FFA),
      monoester waxes (MW), free- and esterified sterols (FST and SE), and squalene
      (SQ) were identified by thin layer chromatography of the lipid materials
      extracted separately from the secretion as well as from the isolated whole glands
      present in the skin of the floor of the external ear canal of the domestic fowl.
      Secretory lipids contained considerable proportions of MW fractions (17.03%), TG
      (22.23%), and SQ (14.66%), while TG was the major component (41.10%) in the
      lipids from the isolated glands. Polar lipids, which comprised about 16-20% of
      total glandular lipids, were shown to be composed primarily of sphingomyelin.

PMID- 9643166
TI  - Melatonin action on thyroid activity in the soft-shelled turtle, Lissemys
      punctata punctata.
AB  - Adult female turtles (Lissemys punctata punctata) were treated with pineal
      indoleamine melatonin (100 micrograms/100 g) or the antithyroid agent,
      methylthiouracil (100 micrograms/100 g) or melatonin together with
      methylthiouracil (100 micrograms of each drug/100 g) for 12 days. Melatonin alone
      inhibited thyroid activity as evidenced by reduction in the gland weight,
      follicular epithelial cell height, thyroid peroxidase, and plasma thyroxine
      levels. Methylthiouracil caused hyperplasia of the gland, although it inhibited
      thyroid activity and reduced thyroid peroxidase and plasma thyroxine levels.
      Melatonin together with methylthiouracil produced changes similar to those
      obtained with melatonin alone. The results indicate that melatonin probably
      exerts inhibitory effects influences on both thyrotropin release from the
      pituitary and the activity of the thyroid itself in turtles.

PMID- 9643167
TI  - Ultrastructural and cytochemical identification of peroxisomes in Balantidium
      coli, Ciliophora.
AB  - Peroxisomes of the trophozoites of Balantidium coli isolated from pig intestine
      content were investigated, using ultrastructural and cytochemical techniques. The
      peroxisomes of B. coli trophozoites from pigs with subclinical balantidiasis are
      less then 0.8 mm in diameter whereas those from pigs with acute balantidiasis are
      greater than 0.8 micron in diameter. In all the trophozoites peroxisomes are
      round, oval or dumb-bell shaped. Catalase as an indicative enzyme was detected by
      cytochemical techniques in B. coli peroxisomes.

PMID- 9643168
TI  - A comparison of nucleic acid content in Balantidium coli trophozoites from
      different isolates.
AB  - Cytophotometric assays were performed on Balantidium coli trophozoites isolated
      from 30 pigs affected by acute balantidiasis (Group I) and from 30 pigs with
      symptom-free balantidiasis (Group II). Trophozoites from cultures obtained from
      Group I and II pig isolates were assayed for comparison. Comparative
      cytophotometric studies on nucleic acids of B. coli trophozoites isolated from
      acute and symptomless balantidiasis-affected pigs as well as from in vitro
      cultured trophozoites showed differences which could have resulted from
      differences between populations in the trophozoans under investigation.

PMID- 9643169
TI  - The "comet" assay for detection of potential genotoxicity of polluted water.
AB  - The aim of this study was to determine the potential genotoxic activity of
      polluted water samples taken from wastewater from selected industrial plants in
      Krakow: 1. the Thermal-electric Power Station 2. the Institute of Metal Cutting.
      The recently developed single cell gel assay (SCG or comet assay), which is a
      quick and simple technique for the evaluation of DNA damage and repair in
      individual cells, was used. The assay was carried out on human hepatoma cells
      (Hep G2) as target cells. A greater number of cells with comets was observed in
      those treated in vitro with the polluted water samples (70%-88%) than in those in
      the control (22%, 33%). These preliminary results indicate that comet assay can
      have an application in biomonitoring studies for determining the potential
      genotoxicity of water pollutants.

PMID- 9643170
TI  - Haematological changes in buprenorphine-treated mice.
AB  - Studies were carried out in adult male Swiss mice to determine whether different
      haematological parameters like total counts of red and white blood cells,
      differential counts of white blood cells, haematocrit value and blood haemoglobin
      level were affected by the synthetic opioid analgesic, buprenorphine, which has
      currently been known to be abused in several countries by the heroin addicts as a
      cheap substitute for heroin. The mice were daily given an intraperitoneal
      injection of buprenorphine (300 micrograms/kg) for 60 consecutive days. A severe
      leucopenia accompanied by decreases in lymphocyte and monocyte counts, an
      increase in neutrophil count, a decrease in haematocrit value, a rossette-like
      adherence of red blood cells to a few neutrophils and platelet satellitism were
      observed at the advanced stages of treatment. The abnormalities, however,
      reverted to normal within 45 days following withdrawal of the drug. The necessity
      of periodic monitoring of the blood picture in human abusers of the drug is
      suggested.

PMID- 9643171
TI  - Prognosis of conventional root canal treatment reconsidered.
AB  - In endodontic literature, the so-called success rate of conventional root canal
      treatment is reported to range between 70% and 95%. This has been calculated as
      the percentage of successfully treated teeth of all teeth followed up or included
      in the clinical trial. This approach, however, does not allow for valid
      assertions on the prognosis of root canal treatment as the individual observation
      times are not considered. This article discusses some methodological and
      statistical aspects of how to design a prognostic study which focuses on the
      outcome of endodontic therapy and of how to analyse the data appropriately.
      Methodologically, the response variable should preferably be the individual time
      required for the occurrence of an event, e.g., success or failure of endodontic
      therapy, which should clearly be defined on the basis of widely accepted criteria
      in endodontology. Event times can appropriately be analysed by the Kaplan-Meier
      method, which estimates the probability that the event will not occur within a
      fixed time. This probability, together with the approximate 95% confidence
      interval (CI), permits an evaluation of the prognosis of a particular treatment.
      Two data sets were re-analysed to clarify the rationale behind the analysis of
      event times. Accordingly, the probability that an endodontically induced lesion
      will completely heal, e.g., within the first 3 years after root canal therapy
      ranges between 0.87 (CI: 0.74-1.00) and 0.89 (CI: 0.80-0.98). In this situation,
      the simple calculation of success rates would overestimate the chance of complete
      periapical healing within the first years after therapy but underestimate it over
      longer observation periods. Another example was used to analyse the time to
      occurrence of periapical pathosis associated with root canal treated teeth not
      diseased periapically. In this case the chance of recording a successful
      endodontic treatment is initially underestimated by the percentage of successful
      cases of all teeth integrated in the study but is markedly overestimated for
      longer observation periods. Potential risk factors affecting the outcome of the
      endodontic therapy and thereby the event times can adequately be determined by
      applying the Cox's or Aalen's regression model.

PMID- 9643172
TI  - Cutting pattern of nickel-titanium files using two preparation techniques.
AB  - The aim of this study was to examine the cutting patterns of recently introduced
      nickel-titanium endodontic files and compare them with similarly shaped stainless
      steel files using both balanced-force and stepback techniques. Simulated canals
      were constructed in resin blocks with 40 degrees curvature. Fifty blocks were
      prepared by a balanced-force technique: 25 with Nitiflex (Maillefer) and 25 with
      Flexofiles (Maillefer) to master apical file size 40. Fifty blocks were prepared
      by a stepback technique: 25 with Nitiflex and 25 with Flexofiles to a master
      apical file size 30. Composite prints were made of pre- and post-instrumentation
      canals using a computerized imaging system. The amount of material removed from
      the inner and outer canal curvatures was measured at eight levels in the apical
      11 mm of the canal. The results were analysed by Kruskal-Wallis ANOVA. Using the
      balanced-force technique, Nitiflex files removed less material on the outer curve
      apically and less on the inner curve mid-canal (P < 0.05), while Flexofiles
      caused more apical transportation. In the stepback technique, the Nitiflex files
      removed more material from the outer curve apically (P < 0.05); the Flexofiles
      removed more material along the entire inner curve (P < 0.05), and maintained
      canal curvature better than Nitiflex files. It appeared preferable to use
      Nitiflex files in a balanced-force technique, and Flexofiles in a filing
      technique as stainless steel files can be precurved.

PMID- 9643173
TI  - An in vitro evaluation of canal preparation using Profile .04 and .06 taper
      instruments.
AB  - A model system involving a double radiographic exposure technique was developed
      in order to evaluate maintenance of the original canal path of curved root
      canals. The mesiobuccal roots of 30 maxillary molars were prepared using one of
      three techniques (n = 10 in each group). One group was instrumented using rotary
      Profile .04 tapers and a second group was prepared using orifice openers, rotary
      Profile .04 and .06 tapers. The final group was prepared using Profile hand files
      .02 taper and Gates-Glidden drills. Canal transportation was evaluated in the
      apical, middle and coronal regions from the double-exposed radiographs. Canal
      shape was determined by the ease with which a D11T spreader passed to within 1 mm
      of the working length. Time of instrumentation was also recorded. The results
      showed no significant difference between the techniques in canal transportation
      in the apical, middle or coronal regions (P > 0.05). It was significantly easier
      to place the D11T spreader in the .06 taper group (P < 0.05). Canal preparation
      was significantly quicker in the .04 taper group (P < 0.05). In conclusion, the
      use of .06 taper files improved canal shape and did not increase transportation.
      The additional file changes, however, increased the instrumentation time.

PMID- 9643174
TI  - In vitro evaluation of the cytotoxicity of a bleaching agent.
AB  - Cell cultures of L929 and BHK21/C13 cells were used to evaluate the toxicity of a
      newly introduced bleaching agent (Colgate Platinum) compared to hydrogen
      peroxide, an established bleaching agent. The cell reaction was determined by a
      quantitative technique at 24 h and 72 h. Both bleaching materials had a dose
      dependent effect on cell viability. Concentrations of hydrogen peroxide causing a
      50% decrease in cell number (50% inhibition dose-ID50) were calculated as
      0.00034% after 24 h and 0.00001% after 72 h in L929 cells. The ID50 of hydrogen
      peroxide was found to be 0.00016% after 24 h and 0.00007% after 72 h in BHK21/C13
      cells. The ID50 of Colgate Platinum was 0.00074% after 24 h and 0.00045% after 72
      h in L929 cells and 0.00055% after 24 h and 0.00024% after 72 h in BHK21/C13
      cells. The results showed that, in vitro, both bleaching agents were cytotoxic to
      fibroblasts and the new bleaching agent was less toxic than hydrogen peroxide.

PMID- 9643175
TI  - Effect of argon laser irradiation on instrumented root canal walls.
AB  - The objective of the study was to examine whether argon laser has a property to
      remove debris and smear layer from root canal walls. Twelve endodontically
      treated human maxillary molar teeth with three root canals were divided into two
      groups of six teeth. The first group was left unlased as a control; in the second
      group the root canals were irradiated by argon laser (laser parameters were set
      at 1 W and pulse duration and pulse frequency fixed at 0.05 s and 5 Hz). After
      the usual root canal preparation and lasing had been carried out, the teeth were
      decoronated, bisected longitudinally, observed with a scanning electron
      microscope and evaluated as to how clean the surfaces of root canal walls were.
      In most cases control teeth presented surfaces with debris covering the root
      canals, obscuring the dentinal tubules. Only 1 of 18 specimens was free of
      debris. In the lased group, root canal surfaces free of debris and vaporized
      pulpal tissue remnants were observed in 13 of 18 specimens. The results showed
      significant statistical differences between the control group and the lased
      groups (P < 0.001). These results suggested that argon laser irradiation has an
      efficient cleaning effect on instrumented root canal surfaces.

PMID- 9643176
TI  - Sequelae of trauma to primary maxillary incisors. I. Complications in the primary
      dentition.
AB  - Two hundred and eighty-seven children with a total of 545 traumatized primary
      upper incisors were followed using standardized procedures until the age of 10.
      Extraction was the only treatment offered when intervention was necessary. The
      immediate as well as the long-term consequences of trauma were studied on the
      basis of this material. Consequences in the primary dentition comprised: color
      changes (53%), pulp necrosis (25%), pulp canal obliteration (36%), gingival
      retraction (6%), permanent displacement after luxation (5-22%), pathological root
      resorption (1-10%) as well as disturbances in physiological root resorption (4%)
      and, lastly, premature tooth loss (46%). In a multivariate analysis of the
      development of pulp necross in primary teeth after trauma, the following decisive
      factors were found: age of the patient at the time of injury, degree of
      displacement of the tooth as well as the degree of loosening and presence of
      crown fracture. The factors found to influence development of pulp canal
      obliteration were: displacement of the tooth at time of injury as well as
      detectable physiologic root resorption at time of trauma. The presence of crown
      fracture seemed to decrease the risk of obliteration. The need for scientifically
      based treatment strategies for managing and reducting complications after trauma
      in the primary dentition is stressed.

PMID- 9643177
TI  - Forces transmitted through a laminated mouthguard material with a Sorbothane
      insert.
AB  - Sorbothane is a visco-elastic polyurethane that has been used in sports and
      orthopaedic applications because of its shock-absorbing properties. The aim of
      this laboratory study was to evaluate the effect of an intermediate layer of
      Sorbothane on the peak force transmitted through two thermoplastic ethylene vinyl
      acetate (EVA) sheets as used in the construction of a custom-made sports
      mouthguard. The EVA sheets were tested at room temperature after thermal
      lamination under pressure, either without (control) or with a Sorbothane
      intermediate layer of 1.1 or 2.65 mm thickness. A piezo-electric transducer was
      used to measure the peak force transmitted through each sample from a free
      falling steel ram. The peak force recorded was significantly less for laminated
      EVA samples with a Sorbothane intermediate layer than for controls of comparable
      thickness. We conclude that a Sorbothane intermediate layer between heat-cured
      laminated EVA sheets, as used in the fabrication of a custom-made sports
      mouthguard, may dissipate significantly the force of impact resulting from a blow
      to the teeth and jaws.

PMID- 9643178
TI  - Complicated crown fracture of an unerupted permanent tooth--a case report.
AB  - Trauma to primary teeth may result in direct damage to underlying developing
      permanent teeth because of the close relationship that exists between the apices
      of the primary teeth and their permanent successors. Injuries to developing teeth
      have been classified into ten different categories, using a classification that
      is largely based on developmental alterations to the permanent teeth. However,
      this classification does not include other types of trauma that may occur to
      developing teeth, such as crown fractures. Although apparently rare, such
      injuries can occur by direct contact of the impacting object with a developing
      tooth, as illustrated by the following case report.

PMID- 9643179
TI  - Splint therapy for skeletal Class III malocclusion in the primary dentition.
AB  - An orthopedic appliance for the correction of skeletal Class III malocclusion in
      the primary dentition is described. The appliance consists of two resin splints
      with hooks for Class III elastic intraoral traction. Construction features and
      biomechanical aspects of the device are described along with the clinical
      evaluation of treatment effects in two case reports.

PMID- 9643180
TI  - Oral rehabilitation in dentinogenesis imperfecta with overdentures: case report.
AB  - A seventeen-year-old girl demonstrating severely worn permanent dentition and
      multiple retained root stumps with dentinogenesis imperfecta is presented.
      Overdentures were made to preserve bone height, re-establish the lost vertical
      dimension of occlusion, to provide acceptable esthetics, and to establish an
      efficient masticatory system.

PMID- 9643181
TI  - A conservative approach to the pulpotomy in primary teeth.
AB  - This study evaluates the importance of preserving the dentinal roof of the pulp
      chamber, when the pulpotomy technique is performed, thus obtaining an important
      reinforcement of the tooth by employing a very simple technique. Therefore, the
      current vertical fracture of the primary molars is avoided even though a steel
      crown is not adapted.

PMID- 9643182
TI  - Class III cavity preparation in primary anterior teeth: in vitro retention
      comparison of conventional and modified forms.
AB  - Management of mild to moderate caries in primary anterior teeth is still a
      problem. Presently, class III composite restorations in primary teeth have
      inadequate retention. The purpose of this in vitro study was to analyze the
      influence of the design of modified class III cavity preparation on the retention
      of the restoration when compared to that of the conventional class III
      preparation. Thirty extracted human primary maxillary central incisors were
      divided into two groups of 15 teeth each. In one group, the conventional
      (triangular) class III design was prepared. The second group, the modified class
      III design, was prepared by adding to the conventional form, 0.5 mm. labial
      reduction on the labial tooth surface. The dentinal bonding agent, Amalgambond,
      was applied to 30 teeth according to instructions of manufacturer. The composite
      resin, Herculite XRV, was inserted into each preparation. All samples were
      mounted in plastic molds and thermocycled. The samples were tested with Instron
      testing machine until restoration failure. Results showed that the mean failure
      load of modified class III restoration group (92.19 +/- 13.6 N) was significantly
      higher from that of conventional class III preparation group (45.61 +/- 9.8 N) as
      tested by Student's independent t-test (P < 0.001).

PMID- 9643183
TI  - Chamfered margin effects on occlusal microleakage of primary molar Class I
      composite resin restorations in vitro.
AB  - Recent clinical studies have suggested that composite resin may be an effective
      restorative material for the restoration of Class I preparation in primary
      molars. The primary objective of this study was to assess the effects in vitro of
      a chamfered margin on occlusal microleakage of class I posterior composite resin
      restorations in primary molars. Two cavity preparations (conventional and
      modified) were compared by using forty extracted primary molars. The modified
      class I preparation as described in this study showed no occlusal microleakage
      and recommended to be further studied clinically. The difference between these
      two groups was analyzed by using the Fisher Exact Probability Test and was
      statistically significant.

PMID- 9643184
TI  - Loss of space and dental arch length after the loss of the lower first primary
      molar: a longitudinal study.
AB  - The premature loss of primary teeth may harm the normal occlusal development,
      although there are debates relating to the necessity of using space maintainer
      appliances. The aim of the study is to evaluate the changes in the dental arch
      perimeter and the space reduction after the premature loss of the lower first
      primary molar in the mixed dentition stage. The sample consists of 4 lower arch
      plaster models of 31 patients, within the period of pre-extraction, 6, 12 and 18
      months after the lower first primary molar extraction. A reduction of space was
      of noted with the cuspid dislocation and the permanent incisors moving toward the
      space of the extraction site. It was concluded that the lower first molar primary
      premature loss, during the mixed dentition, implicates an immediate placement of
      a space maintainer.

PMID- 9643185
TI  - Estimated skin exposure as an indicator for comparing radiovisiography (RVG)
      versus conventional Ektaspeed Plus dental radiography.
AB  - An Everest 3000 Radiovisiography (RVG) Video system (Trophy USA Inc.,
      Fredericksburg, VA 22402) was compared with conventional radiography using
      Ektaspeed Plus film (Eastman Kodak Co., Rochester, NY 14650). Previous studies of
      the RVG system with a special computer controlled x-ray timer (Trophy USA, Inc.)
      claimed a significant reduction in radiation. Trophy has also claimed that the
      RVG system can provide diagnostic quality images utilizing existing conventional
      x-ray generators. This study used a conventional timer and generator. Since it
      would be logical to assume that many practitioners would use the equipment "in
      place" rather than invest in new, unfamiliar equipment. Estimated Skin Exposure
      (air) was used as the primary criteria for comparative purposes. Exposure has
      been defined as "a measure of radiation quantity, the capacity of ionize air. The
      roentgen (R), is the traditional unit of radiation exposure measured in air"; The
      results indicate that the RVG system when combined with a standard conventional
      timer actually generated greater radiation exposure than does standard, routine
      radiography.

PMID- 9643186
TI  - Orthodontic treatment priority: a comparison of two indices.
AB  - Approval for state sponsored funding of orthodontic treatment is often decided
      using an index of malocclusion. The purpose of this study was to determine
      whether two indices used for prioritizing patients would identify different
      groups of individuals qualifying for orthodontic treatment funding approval. In
      addition, the characteristics of patients approved using different indices were
      compared. The records of 40 patients previously submitted for state medicaid
      funding approval were evaluated by three study examiners using two orthodontic
      treatment priority indices, the Salzmann Handicapping Malocclusion Assessment
      (Salzmann) and the Index of Orthodontic Treatment Need (IOTN). Comparisons were
      made between state medicaid and study examiner Salzmann scores, rankings, and
      funding decisions, and between study examiner Salzmann rankings, IOTN rankings,
      and funding decisions. Correlation and rank correlation coefficients between the
      state and study examiners' Salzman scores were high (r = 0.74; p < 0.001, and R =
      0.77; p < 0.001). Rank correlation analysis of the study examiners' Salzmann and
      IOTN values demonstrated a weaker relationship (R = 0.40; p < 0.02). Agreement on
      funding decisions, evaluated by the Kappa statistic, was greater between the two
      Salzmann evaluations (K = 0.57) than between the study examiners' Salzmann and
      IOTN evaluations (K = 0.14). As expected, depending on the method used to
      determine orthodontic treatment funding priority, different patients were likely
      to be identified for treatment approval. The characteristics of patients whose
      treatment was approved was closely related to the criteria defined by the method
      employed.

PMID- 9643187
TI  - Profile of non-nutritive sucking habits in relation to nursing behavior in pre
      school children.
AB  - Although a number of investigators have studied the prevalence and etiology of
      non-nutritive sucking habits in children, no consensus exists among dental and
      medical experts in respect to the contributing factors and preventing behaviors.
      Furthermore, changes in the rearing practices of children make management of such
      habits even more complicated. The purpose of the present study was to investigate
      finger and pacifier sucking habits among pre-school children, and its possible
      relationship to nursing behavior. Parental attitudes towards sucking habits were
      also registered. Questionnaires were sent to parents of 600 children, three to
      five years old, following an oral examination in a private office. Children
      attended kindergartens that were randomly selected from the area of Athens,
      Greece. Questions regarding the nursing patterns-breast or bottle feeding
      characteristics of finger and pacifier sucking habits, parental attitudes towards
      sucking habits, as well as recommendations of the pediatricians were included.
      Three hundred and sixteen questionnaires were returned by parents. Results
      indicated that pre-school children discontinued a pacifier sucking habit earlier
      compared to a finger habit. Pacifiers showed a preventive effect against finger
      sucking, since only 2% of the sample examined practiced both habits. Breast
      feeding was not clearly associated with sucking habits; however, long bottle
      feeding periods were related with decreased finger sucking and high figures of
      pacifier sucking. The majority of pediatricians were not in favor of an
      intervention in breaking a finger sucking habit of the child.

PMID- 9643188
TI  - Inhaler medicament effects on saliva and plaque pH in asthmatic children.
AB  - The purpose of the present study was to investigate the effect on saliva and
      plaque pH of beta 2 agonist (salbutamol 400 mcg) and inhaler corticosteroid
      (fluticasonepropionate 250 mcg). The interproximal plaque pH responses to these
      medicaments and examine the effect of chewing gum after the usage of these
      inhalers. Thirty children of both sexes, from six to fourteen years old,
      participated in the study. The pH microelectrode was used in the study. The
      interdental sites chosen were those between the premolars in the 4 quadrants. The
      pH measurements were made baseline and 1, 5, 10, 20, 30 minutes after the use of
      medicaments as inhaler and also saliva was stimulated by sugar free chewing gum
      (Vivident). Data analyses were conducted using a statistical package through the
      University's computing center. The resulting pH values decreased in all four
      plaque sites and saliva during 30 minutes after inhaler drugs. After rinsing with
      water, the pH values also decreased (p < 0.001). Decreasing pH increased with
      chewing gum (p < 0.001). The hypothesis is that a decrease in pH in medicated
      asthmatics could be caused by inhaler drugs. Conclusive evidence for the relative
      role of the disease and the drug in saliva secretion and composition seems to
      require a longitudinal study on asthmatics before and after the onset of drug
      administration. We suggest that children with bronchial asthma treated with
      inhaler drugs should receive special preventive attention.

PMID- 9643189
TI  - Neutrophil chemotaxis in Down syndrome and normal children to Actinobacillus
      actinomycetemcomitans.
AB  - During the last decade a lot of attention has been diverted to the study of
      Actinobacillus actinomycetemcomitans (Aa) as the principal micro-organism in the
      pathogenesis of periodontal disease. Because of the defective body defenses,
      there is an increased likelihood of periodontal disease among the Down syndrome
      patients. An attempt has been made herein to correlate the relationship between
      the gingival and periodontal health status to the isolation of Aa from the
      subgingival plaque in Down syndrome cases and to compare it to the neutrophil
      chemotactic activity to the normal subjects. Strong association between the
      occurrence of Aa as well as significant differences between the healthy and Down
      syndrome subjects in neutrophil defense activity were observed.

PMID- 9643190
TI  - Dermatoglyphic findings in dental caries: a preliminary report.
AB  - The dermatoglyphs of caries-free students and the students with dental caries in
      10 or more teeth were compared. The caries-free students had an increased
      frequency of ulnar loops on all fingers. In contrast, the students with dental
      caries had an increased frequency of whorls on all fingers.

PMID- 9643191
TI  - "9-year-molars" aberrantly developing and erupting: report of cases.
AB  - This paper describes delayed development and eruption of the first permanent
      molars, in most cases only in the upper jaw. The development and eruption of the
      teeth are chronologically between that of the first and second molars. The
      anatomy of the aberrant teeth is closest to that of the second molars. The
      aberrant teeth are often laying at a distance during development from the second
      primary molars. The clinical implications of the aberrancy are few, because the
      teeth will normally migrate into close contact with the tooth mesial to them,
      however, often into a crossbite. Most often the teeth are mistaken to be a first
      molar with some eruption disturbance and therefore referred for surgical or
      orthodontic treatment. However, such interception should be avoided because at
      least in the present cases all teeth are observed to erupt by themselves.

PMID- 9643192
TI  - Dentigerous cyst of mandibular second premolar in a five-year-old girl, related
      to a non-vital primary molar removed one year earlier: a case report.
AB  - A dentigerous cyst of the mandibular second premolar in a 5-year-old female was
      radiographically diagnosed. A non-vital primary predecessor molar had been
      removed a year earlier. At that time, the primary molar had been in the mouth for
      approximately two years. Although there was the possibility of the premolar being
      non-vital, as a consequence of the cystic cavity surrounding it, marsupialization
      treatment of the cyst was done, causing a rapid development of the premolar.
      Structural irregularities in the enamel and in the first radicular portion were
      visible, possibly caused by the very early beginning of the cyst formation.

PMID- 9643193
TI  - Oral manifestations of Ellis-van Creveld syndrome: report of two siblings with
      unusual dental anomalies.
AB  - Ellis-van Creveld syndrome (EvC), also called chondroectodermal dysplasia, is a
      rare occurrence inherited as an autosomal recessive disease. Despite the fact
      that oral manifestations play an important role in the diagnosis criteria for
      EvC, few detailed reports have been published in the dental literature. This
      articles presents two siblings with EvC, a boy aged 9 years and a girl aged 7 1/2
      years, a product of unaffected first cousin parents. The patients manifests:
      chondrodysplasia of tubular bones resulting in disproportionate dwarfism,
      polydactyly and syndactyly of hands and feet, severe dystrophic nails, multiple
      broad labial frenula with abnormal attachments, congenital missing incisors,
      anomalous teeth, bilateral partial clefts of the alveolar bone, and malocclusion.
      Other features noted in either cases are: congenital heart defect, median notch
      of the upper lip, shovel-shaped incisors and taurodontism. Of the unusual dental
      findings observed in our patients are talon cusp, reduced crown size,
      supernumerary tooth, and early eruption of teeth. Because half of the cases with
      EvC have cardiac malformation, dental treatment must be performed under
      prophylactic antibiotic coverage. Dentists play an important role in early
      diagnosis and control of dental problem of this condition.

PMID- 9643194
TI  - Formaldehyde in dentistry: a review for the millennium.
AB  - This article reviews the history and use of formaldehyde in dentistry. Research
      from outside the dental field is included, particularly those articles that
      pertain to mutagenicity and carcinogenicity. The controversies over the use of
      formocresol continue, despite overwhelming research citing deleterious effects.

PMID- 9643195
TI  - Treatment of Class III malocclusion with the horseshoe appliance: case reports in
      growing patients.
AB  - The horseshoe appliance was developed by Dr. Schwarz, and is used to correct
      sagittal relationships by elastic force in patients with Class III malocclusion.
      The horseshoe appliances minimize the increment of lower anterior facial height
      and allow the mandible to be repositioned harmoniously with the soft tissue and
      muscle matrix of the jaw. It has the advantages of good patient cooperation, ease
      of construction, and effective modification. In patients who were treated with
      the horseshoe appliance, the following results were observed: 1. Forward growth
      of the maxilla was enhanced, overgrowth of the mandible was restricted, and a
      normal arch relationship was established. 2. Minimum downward and backward
      rotation of the mandible was accepted with the free sliding of the appliance, and
      elastic force and increment of lower anterior facial height were minimized. 3.
      Both labioversion of maxillary incisors and linguoversion of mandibular incisors
      were observed and facial profile was improved.

PMID- 9643196
TI  - Treatment of Class III orthodontic cases in childhood: case report.
AB  - Two Class III cases are described which are treated first during childhood with
      orthopedics and later by a second stage with orthodontics using bonded braces.
      One case was treated solely with a chin cup and the other with a chin cup,
      disjunction and anterior traction. Profile and occlusion changes are analyzed and
      the orthopedic effect of the treatment is discussed.

PMID- 9643197
TI  - The management of premolar supernumeraries in three orthodontic cases.
AB  - This paper reviews the incidence, etiology and location of supernumerary teeth
      with emphasis on premolar supernumeraries and examines the management of
      supernumerary premolars of three patients undergoing orthodontics. These cases
      demonstrate that the management of premolars is assessed individually and
      treatments based on potential complications, which may occur during the
      orthodontic and surgical management of the dentition. Progress and posttreatment
      radiographs are recommended for the assessment of late forming supernumerary
      teeth.

PMID- 9643198
TI  - Suture splint: an alternative for luxation injuries of teeth in pediatric
      patients--a case report.
AB  - Stabilization of replanted tooth "splinting" is done to prevent further damage to
      the pulp and periodontal structure during the healing period. Suture and bonded
      resin splint is passive, semirigid and functional splint. It is easy to fabricate
      directly in mouth without lengthy laboratory procedures. A case is presented in
      which suture and bonded resin splint was performed on laterally luxated maxillary
      central incisor and avulsed lateral incisor. The splint was removed after one
      week and sufficient periodontal and gingival healing was observed.

PMID- 9643199
TI  - Child abuse: attitudes and perceptions of health profession students--a pilot
      study.
AB  - Child abuse and neglect is a serious social problem with global dimensions. The
      purpose of this study was to assess attitudes and perceptions of students of
      medicine, dentistry and public health at three Boston institutions about child
      abuse and neglect issues that they may encounter in their future professional
      lives. Among others, we investigated how participants rank the public health
      importance of child abuse and neglect in comparison with violent acts against
      other social groups, their willingness to report it and their potential interest
      to supplement their knowledge with additional course work. Two hundred and
      fourteen students participated in the study by completing our questionnaire. The
      results of the statistical analyses indicate that child abuse is considered the
      most serious problem, followed by domestic violence, child neglect and abuse of
      the handicapped and the elderly. We also documented that a significant
      educational need exists in this group, regarding diagnostic methods and
      interventions aimed to reduce the incidence and the impact of violence or neglect
      against children.

PMID- 9643200
TI  - Marsupialization of dentigerous cyst associated with foreign body using 3D CT
      images: a case report.
AB  - This paper documents a marsupialized dentigerous cyst associated with an amalgam.
      The surgical challenge was removing the amalgam from the cystic lining with zero
      visibility. To achieve this, the surgical procedure was computer assisted and
      used 3D images. Distances between the amalgam and various anatomical landmarks
      were assessed in order to define a path from the top of the ridge to the amalgam.
      The path was reconstructed at the surgical site and the amalgam removed by
      suction. Orthodontic treatment was associated with surgery. Three dimensional
      imaging is a useful procedure for deciding on the type of surgical technique
      likely to minimize trauma. This report is also a contribution to the literature
      by reporting two dentigerous cysts associated with amalgam.

PMID- 9643201
TI  - Transposition of maxillary permanent left cuspid tooth: a case report.

PMID- 9643202
TI  - Taurodontism in children associated with trisomy 21 syndrome.
AB  - Taurodontism, the dental trait characterized by teeth with elongated pulp
      chambers and apical displacement of the bifurcation or trifurcation of roots, is
      reviewed in children with Trisomy 21 (Down) syndrome. Twenty-two patients were
      studied to determine the frequency of taurodontism. Eruption delay and
      congenitally lost teeth were also evaluated. While no taurodont teeth were found
      in control group in the same age group, the frequency percentage of taurodontism
      in our study was found as 66% (p < 0.01, Mann-Whitney test). Results indicate
      that taurodontism occurs with a greater than expected frequency in these
      patients. This increased frequency may be from a generalized amplified
      instability of development.

PMID- 9643203
TI  - Late development of maxillary supernumerary tooth: a case report.
AB  - A case is presented of a late developing maxillary supernumerary tooth in the
      permanent dentition. The patient had a supernumerary tooth fused to a central
      incisor in the primary dentition. This case emphasizes the importance of careful
      follow-up of patients with a history of supernumerary teeth and, where clinically
      indicated, of further radiographic examination.

PMID- 9643204
TI  - Fluoride release from fissure sealants.
AB  - This 30-day study, compared the amounts and patterns of fluoride release from 5
      commercially available fluoride-containing pit and fissure sealants: FluroShield,
      Helioseal-F, Ultraseal XT, Baritone L3, and Teethmate-F; Delton without fluoride,
      was used as control. Disc-shaped samples of each sealant were immersed in
      distilled water and the fluoride release was measured periodically until day 30.
      All the fluoridated sealants tested released measurable fluoride throughout the
      test period in a similar pattern: the greatest amount of fluoride was released in
      the first 24 hours after mixing, fell sharply on the second day and decreased
      slowly for the last days. On day one, Baritone L3 released significantly more
      fluoride than all other materials. Teethmate-F released the highest amount of
      fluoride during all the other time intervals from day 2, until day 30.

PMID- 9643205
TI  - The marginal seal of various restorative materials in primary molars.
AB  - The use of resin composite restorations in posterior teeth has become an accepted
      clinical procedure. Microleakage at the posterior composite/tooth interface is a
      major problem. The in vitro quality of the marginal seal was tested in eighty
      teeth extracted for orthodontic reasons using a glass-ionomer cement reinforced
      with amalgam, two light self-curing glass-ionomer cements and a compomer. All the
      teeth were subjected to thermocycling to simulate clinical situation. Compomers
      showed the best mechanical and esthetic properties combined with a good marginal
      seal.

PMID- 9643206
TI  - Cuspal fracture resistance and microleakage of glass ionomer cements in primary
      molars.
AB  - The purpose of this study was to comparatively evaluate the fracture strength and
      microleakage among two new glass ionomer cements. One hundred and ten primary
      first and second molars were divided into two main groups, one group comprising
      of fifty teeth for microleakage evaluation and second group of sixty for fracture
      strength. Both the groups were subdivided equally into four based on the
      materials used, consisting of the same number of teeth respectively, in each. Two
      controls were used for cuspal fracture strength and an additional trial group was
      added for microleakage evaluation. Ideal, non retentive class II were prepared
      and restored with amalgam, Fuji IX, Fuji II LC and Vitremer. The statistical
      analysis revealed highly significant differences among all the subgroups except
      between subgroup 3 vs. 4 and 1 for cuspal fracture strength. Similarly
      microleakage values were significantly different statistically among sub groups 4
      and 5 vs 1 and 2. The present study revealed that Fuji IX was the best in terms
      of cuspal fracture strength and Fuji IX with an additional application of light
      cure resin sealant gave the lowest degree of microleakage.

PMID- 9643207
TI  - Progression of interproximal caries in the primary dentition.
AB  - While studies have addressed the diagnosis and progression of interproximal
      carious lesions within a primary tooth, few studies have addressed the
      development of proximal lesions in adjacent primary molars. The purpose of this
      study was to examine retrospectively the long term interproximal caries
      progression in primary molar teeth. Dental records of 150 children were
      retrospectively reviewed, 76 from a university pediatric dentistry clinic and 74
      from a pediatric dentistry private practice. Out of the 387 teeth initially
      diagnosed with proximal caries, the combined university and private practice
      results for timing of the development of proximal lesions on adjacent tooth
      surfaces showed the following: simultaneous development-162 (41.9%); 1 to 24
      months-65 (16.8%); 24 to 60 months-40 (10.3%); never-120 (31.0%). The combined
      results for formation of proximal caries in posterior quadrants showed that out
      of the 150 patients, the timing for development of additional quadrants with
      proximal caries was as follow: simultaneous development: 77 (51.3%); 1 to 24
      months 31, (20.7%); 24 to 60 months 25, (16.7%); never 17 (11.3%). The
      conclusions of the study are that 69% of the primary molar teeth with proximal
      caries developed caries on the adjacent proximal surface and 89% of the patients
      who developed a proximal carious lesion on a primary molar tooth within one
      quadrant developed another primary molar proximal lesion in another quadrant.

PMID- 9643208
TI  - Regressive changes of the dental pulp complex in retained primary molars with
      congenitally missing successor teeth.
AB  - This study was undertaken to investigate the regressive changes occurring in the
      dental pulp complex (pulp, dentin, and cementum) of retained mandibular primary
      second molars with congenitally missing bicuspid teeth. Seventeen retained,
      caries free, primary molars were used. The specimens were fixed in 10% neutral
      buffered formalin. Fixed samples were decalcified, routinely prepared, embedded
      in paraffin, sectioned, and stained with hematoxylin and eosin. The results
      demonstrated a reduction in the pulp size, abnormal odontoblastic pattern,
      declined vascularity, pulp degeneration, pulp stones, accelerated formation of
      secondary dentin, and hypercementosis. This study suggests that these findings
      may be from aging and physiological defensive changes. These normal, age-induced
      changes are of considerable importance in the fields of endodontics,
      orthodontics, and pediatric dentistry.

PMID- 9643209
TI  - Comparison of two dentin adhesives to primary vs. permanent bovine dentin.
AB  - The purpose of this study was to compare the shear bond strengths of two adhesive
      systems to the primary and permanent dentin. Labial surfaces of extracted and
      frozen bovine mandibular primary incisors and permanent incisors were ground with
      #600 grit SiC paper to expose dentin. Bisco Dental Products All Bond 2 (Group
      AB2) or Sunmedical Co. Superbond D Liner (Group SDL) tooth surface conditioner
      and adhesive were applied and bonded with resin composite. A shear bond strength
      (SBS) test was performed and the data were analyzed by an ANOVA (P < 0.05). After
      the SBS test, the test surfaces of the dentin and the resin were observed using
      SEM. SBS on the primary dentin were significantly higher than those on the
      permanent dentin, both in the nonthermal cycled groups and the thermal cycled
      groups with the exception of the thermal cycled group of Group SDL. In the
      thermal cycled group of Group SDL, there was no significant difference between
      SBS on the primary dentin and SBS on the permanent dentin. Bond strengths on the
      primary dentin were found to be significantly higher than those on the permanent
      dentin, when using All Bond 2 or Superbond D Liner adhesive systems.

PMID- 9643210
TI  - The effect of chewing gums on acidogenicity of plaque after a sucrose challenge.
AB  - The aim of this investigation was to study the effect of chewing sugared, sugar
      free or gum with therapeutic agents like urea or fluoride, on pH of dental plaque
      after a sucrose challenge using a microtouch method. The 20 subjects aged 8 to 10
      years refrained from toothbrushing for 2 days. Resting plaque pH was recorded,
      followed by sucrose 10% (w/v) rinse for 3 min. After 5 min chewing gum was given
      and pH recorded at time points of 5, 10, 20, 30 min. Highest plaque pH was found
      with Endekay (urea) at all time points followed by fluoride chewing gum; Trident,
      and Wrigley's (p < 0.0001). Sucrose 10% w/v (control) showed the maximum drop in
      plaque pH when compared to the rest of the groups. The comparative evaluation has
      shown Endekay having maximum pH against the acidogenic challenge. Therefore the
      present study indicates that chewing gum containing therapeutic agents like urea
      may be recommended in high risk caries children.

PMID- 9643211
TI  - Cleidocranial dysostosis: report of a case.
AB  - This case of cleidocranial dysostosis showed nearly 40 accessory teeth and the
      unerupted teeth on radiological examinations. Other diagnostic procedures found
      hypoplasia in maxillary and zygomatic bones, deep palate, open fontanel and open
      sutures, the collapse of sagittal suture, and aplasia of the clavicle. There were
      some abnormalities of the fingers. Under general anesthesia eleven supernumerary
      teeth in the mandible and eight in the maxilla were surgically extracted. Upper
      and lower removable acrylic appliances were fabricated.

PMID- 9643212
TI  - Pediatric malocclusion: early treatment versus late treatment.

PMID- 9643213
TI  - The causes of dental erosion.

PMID- 9643214
TI  - HIV topic update: salivary testing for antibodies.
AB  - Salivary antibody testing for HIV is proving to be a sensitive and specific
      procedure, especially useful for epidemiological studies, and has the advantages
      of being simple and non-invasive. This paper reviews the field and discusses
      antibody testing of dental patients.

PMID- 9643215
TI  - Oral disease in Africa: a challenge to change oral health priorities.
AB  - Colonial and other unsustainable oral health strategies exported to Africa have
      failed to improve oral health in the region. An alternative way of interpreting
      and responding to the problems of oral health in Africa is presented. It begins
      with a systematic interpretation of the health information available, using the
      application of the basic epidemiological principle of defining a specific health
      problem by describing its prevalence, severity (morbidity, mortality) and age
      adjusted distribution in the population. African oral disease priorities
      determined in this way are shown to be fundamentally different from those
      perceived previously. It is recommended that this new approach be used in
      customising a viable set of oral health policies and intervention strategies for
      each individual African community.

PMID- 9643216
TI  - Human genes for dental anomalies.
AB  - The development of the tooth at gene level is beginning to be understood. This
      paper reviews current knowledge and the advances in research on human genes whose
      defect leads to dental anomalies. Amelogenesis imperfecta (AI) is a diverse group
      of hereditary disorders characterized by a variety of developmental enamel
      defects including hypoplasia and hypomineralization, some of which have been
      revealed to be associated with defective amelogenin genes. The human amelogenin
      genes on X and Y chromosomes have been cloned and investigated extensively.
      Although autosomally inherited forms of AI are more common than the X-linked
      forms, most studies on the genes causing AI have been performed on the genes of X
      linked forms. Recently, the gene for the human tuftelin protein (an enamelin) has
      been cloned as a candidate gene for the autosomal forms of AI with another gene
      on chromosome 4 involved in some families. Dentinogenesis imperfecta (DI) may be
      associated with osteogenesis imperfecta (OI), which is an autosomal dominant bone
      disease. Most patients with OI have mutations in either the COLIA1 or COLIA2
      genes, which encode the alpha 1(I) or alpha 2(I) subunits of type I collagen, the
      major organic component of bone and dentin. Gene defects causing isolated DI have
      not been identified. Recently, it was demonstrated that a missense mutation of
      MSXI, a human homeobox gene, causes autosomal dominant agenesis of second
      premolars and third molars. Data indicating an important function for MSXI, the
      mouse counterpart of the human MSXI gene, in mouse tooth development have been
      accumulating since 1991. Knockout mice lacking this gene exhibited multiple
      craniofacial anomalies including complete tooth agenesis. X-linked anhidrotic
      ectodermal dysplasia (EDA), characterized by abnormal hair, teeth, and sweat
      glands, was demonstrated to be caused by a mutation in a novel transmembrane
      protein gene that is expressed in epithelial cells and in other adult and fetal
      tissues. The predicted EDA protein may belong to a novel class of proteins with a
      role in epithelial-mesenchymal signaling. Several mutations have been reported in
      genes causing hypophosphatasia, which is characterized by defective
      mineralization of the skeletal and dental structures.

PMID- 9643217
TI  - Parathyroid hormone-related protein (PTHrP) as a regulating factor of
      endochondral bone formation.
AB  - Parathyroid hormone-related protein (PTHrP) was first identified as a
      pathogenetic factor for the hypercalcemia of malignancy. Recently PTHrP is
      focused as a physiological paracrine factor regulating cell proliferation and
      differentiation in many tissues during fetal and postnatal growth. Evidence for
      the skeletal origin of PTHrP comes from several sources and targeted disruption
      of the PTHrP gene in mice has resulted in a phenotype with accelerated
      endochondral bone formation, suggesting PTHrP as a factor regulating chondrocyte
      differentiation. Indian hedgehog, one of the conserved family of hedgehog
      regulating segmentation of Drosophila, is found to be an upstream factor of PTHrP
      in a regulating pathway of chondrocyte differentiation. Moreover, Bcl-2, a
      protein that controls programmed cell death in several cell types, is suggested
      to lie downstream of PTHrP in this pathway. A point mutation of PTH/PTHrP
      receptor is identified in a patient with Jansen-type metaphyseal chondrodysplasia
      and constitutive, ligand independent activation is indicated in this mutant
      receptor.

PMID- 9643218
TI  - Cancer-promoting effect of Taiwan betel quid in hamster buccal pouch
      carcinogenesis.
AB  - OBJECTIVE: To investigate the cancer-promoting effect of Taiwan betel quid in
      hamster buccal pouch carcinogenesis. MATERIALS AND METHODS: Two hundred and fifty
      two non-inbred male adult Syrian golden hamsters were randomly divided into six
      groups, each containing forty-two animals. A treatment regimen over a 14-week
      experimental period was employed with six animals per group being killed at seven
      different periods (every 2 weeks). The right buccal pouch of each animal was
      painted three times a week with various combinations of 7,12
      dimethylbenz[a]anthracene (DMBA), Taiwan betel quid extract, dimethyl sulfoxide
      (DMSO) and mineral oil. RESULT: Both the number and size of tumors in animals
      concurrently treated with DMBA and betel quid were significantly higher than
      those in animals treated with DMBA alone in each killing period of 8, 10, 12 and
      14 weeks. No visible tumors but hyperkeratosis and acanthosis were observed in
      pouches treated with betel quid alone for all killing periods. CONCLUSION: Our
      results indicate Taiwan betel quid may be a co-carcinogen in human oral
      carcinogenesis, if extrapolation can be made from the current animal study.

PMID- 9643219
TI  - The association of platelet-derived growth factor (PDGF) receptor tyrosine
      phosphorylation to mitogenic response of human osteoblastic cells in vitro.
AB  - OBJECTIVES: The purpose of this study was to make clear the relationship of human
      osteoblastic cell growth, induced by platelet-derived growth factor (PDGF), to
      PDGF receptor tyrosine phosphorylation. MATERIALS AND METHODS: Osteoblastic cells
      derived from human maxilla were cultured with human PDGF. The cell growth was
      evaluated by cell number and DNA synthesis. PDGF receptor tyrosine
      phosphorylation was detected by immunoblot analysis using anti-PDGF receptor
      alpha, beta subunits and anti-phosphotyrosine antibodies. Genistein, a tyrosine
      kinase inhibitor, was added to the culture to investigate the effect on
      osteoblastic cell growth and PDGF receptor tyrosine phosphorylation induced by
      PDGF. RESULTS AND CONCLUSIONS: PDGF stimulated the proliferation of human
      osteoblastic cells and this effect was synergetic with serum stimulation. DNA
      synthesis of osteoblastic cells was elevated by PDGF in a dose dependent manner
      at the minimum concentration of 1 ng ml-1. PDGF also induced PDGF receptor
      tyrosine phosphorylation within 1 min on osteoblastic cells, and tyrosine
      phosphorylation occurred on PDGF receptor subunits alpha and beta. Genistein
      inhibited cell growth and receptor tyrosine phosphorylation, which was induced by
      PDGF on these cells. In conclusion, human osteoblastic cell growth induced by
      PDGF is shown to relate to tyrosine kinase of PDGF receptors.

PMID- 9643220
TI  - The use of tretinoin as oral mucositis prophylaxis in bone marrow transplantation
      patients: a preliminary study.
AB  - OBJECTIVE: The examination of prophylactic efficacy of tretinoin on oral
      mucositis, post bone marrow transplantation (BMT). PATIENTS AND METHODS: The
      study population consisted of 11 patients undergoing BMT. Six tretinoin topically
      treated patients (0.25 mg daily of 0.1% tretinoin cream) were matched with five
      non-treated control patients comparing mucositis severity, duration and analgetic
      (morphine) requirements. Concomitant follow-up included conditioning parameters
      associated with mucositis and engraftment. RESULTS: The mean of oral mucositis
      peak scores was significantly lower in the tretinoin-treated patients vs the non
      treated patients (score 1.5 vs 3.6; P < 0.02). In the majority of cases the
      duration of the most severe phase of oral mucositis was shorter in the tretinoin
      treated group as compared with the control. Only one patient in the experimental
      group required morphine analgesics compared with four patients in the control
      group. CONCLUSIONS: This preliminary study indicates that the severity of oral
      mucositis, both objective and subjective, in BMT patients may be reduced by 0.1%
      topical tretinoin cream, 0.25 mg, administered daily from the beginning of the
      BMT conditioning regimen until marrow engraftment.

PMID- 9643221
TI  - Intranodal injection of anticancer drugs into fixed cervical metastatic lymph
      nodes.
AB  - OBJECTIVE: In patients with head and neck carcinoma, fixed enlarged metastatic
      lymph nodes (LNs) are sometimes inoperable and carry an increased risk of
      mortality. To control metastatic LNs, we attempted intranodal injection of
      anticancer agents. SUBJECTS AND METHODS: Fifteen patients with squamous cell
      carcinoma arising in the gingiva (8), tongue (3), floor of the mouth (1), or
      maxillary sinus (3) were enrolled. These patients consisted of two groups, those
      in the early era in which the fixed LNs of six patients were treated with 60Co
      (RA group) and those in the late era in which both radiation and intranodal
      injection of anticancer agents were administered to nine patients (IN group).
      Intranodal injection consisted of peplomycin, 5-fluorouracil, and cis
      diamminedichloroplatinum. RESULTS: In the IN group, LNs regressed from about 40%
      to nearly 100%, although two patients showed no appreciable response. The LNs
      treated by combination therapy regressed considerably while LNs in the same
      patients treated with 60Co alone showed a minor response or grew gradually. In
      three patients, the LNs regressed sufficiently to be extirpated safely. The good
      clinical response in the locally injected LNs was histologically associated with
      distinct evidence of tumor cell degeneration. In the RA group, none of the LNs
      responded to radiation with 60Co; one LN exhibited slight regression, but the
      others enlarged during and soon after the radiation. Compatible with the clinical
      effects, many patients in the IN group demonstrated a good prognosis; three are
      alive without disease, and four survived for prolonged periods. However, all
      patients in the RA group died due to progression of the positive LNs or pulmonary
      complication within 10 months. CONCLUSION: These results indicate that intranodal
      injection of anticancer drugs is useful for the management of fixed enlarged LNs.

PMID- 9643222
TI  - Characteristics of rheumatoid arthritis patients with self-reported sicca
      symptoms: evaluation of medical, salivary and oral parameters.
AB  - OBJECTIVES: To examine the prevalence of sicca symptoms in rheumatoid arthritis
      (RA)-patients, and to evaluate medical, salivary, and oral parameters in matched
      subgroups of patients with and without sicca symptoms as well as in healthy
      controls. PATIENTS AND METHODS: The prevalence of self-reported sicca symptoms
      was examined by a postal questionnaire in a representative cohort of RA-patients
      (n = 105, aged 52-74 years, disease duration 10-20 years, 77% females, 56% RF
      positive). Patient subgroups and controls (9-10 in each group) underwent
      examinations of disease activity, blood analyses, tests of tear and salivary
      secretion, and examination of oral mucosa and microflora. Analyses of salivary
      acidic proline-rich proteins (PRPs), statherin and histatins were performed.
      RESULTS: One or more sicca symptoms were reported by 65% of RA-patients. Sicca
      patients (having > or = 4 sicca symptoms) had a more active and severe disease
      with higher scores for disability, fatigue and tender joints than patients
      without such symptoms. Other significant findings in the sicca group were lower
      values of unstimulated whole saliva, output of PRPs, statherin and histatins in
      submandibular saliva, and higher counts of oral Candida species. CONCLUSIONS:
      Sicca symptoms were prevalent in RA. Qualitative and quantitative salivary tests
      distinguished between sicca and non-sicca RA-patients, though overlap was
      considerable for some parameters.

PMID- 9643224
TI  - Dental erosions and gastro-oesophageal reflux disease in institutionalized
      intellectually disabled individuals.
AB  - OBJECTIVE: Both exogenous acids, from the diet, and endogenous acids, from
      stomach juice, can dissolve the enamel mineral, resulting in dental erosions.
      Gastric acid may reach the mouth by gastro-oesophageal reflux disease (GERD),
      recurrent vomiting, rumination and regurgitation. These conditions are frequently
      found in the intellectually disabled population. Therefore, we investigated the
      presence of dental erosions in combination with GERD among intellectually
      disabled inhabitants, with an IQ < 50, taken from three Dutch institutes.
      MATERIALS AND METHODS: At random 63 individuals underwent an oesophageal pH test
      and dental screening and possible predisposing and attributable factors were
      determined. An abnormal pH level was defined as a pH < 4, > 4.5% of the measured
      time. Subjects with dental erosions were compared to those without dental
      erosions. RESULTS: In 29 out of 63 (46.0%) cases evidence of dental erosions was
      found. In 19 of these 29 subjects with erosions (65.5%) GERD was diagnosed,
      compared to nine (26.5%) out of 34 subjects without erosions (P = 0.04). In the
      subjects with erosions mean duration of pH < 4 was 15.6% (range: 0.5-90.5)
      compared to 6.3% (range 0-40.4) in subjects without erosions (P = 0.02). An IQ <
      35 was found to be predisposing (P < 0.001). CONCLUSION: In this population of 63
      institutionalised intellectually disabled persons dental erosions were diagnosed
      in 46%. Sixty-five per cent of them had GERD. Individuals with longer duration of
      pH < 4 than 6.3% of the measured time and with an IQ < 35 were at higher risk to
      develop dental erosions. This study shows that dental erosions in the
      intellectually disabled population might be an oral manifestation of GERD.

PMID- 9643223
TI  - Characteristics and responses of EBV immortalized B cells from periodontal
      disease patients.
AB  - OBJECTIVE: This study was designed to examine human B cell responses to
      Actinobacillus actinomycetemcomitans (Aa). The general hypothesis to be tested
      was that Epstein-Barr virus (EBV) immortalized B cells could be used to
      investigate variations in B cell responsiveness of periodontitis patients to
      periodontal pathogens, and that B cells derived from the peripheral blood of
      periodontal disease patients infected with Aa demonstrate differences in in vitro
      activities compared to periodontally healthy subjects. DESIGN: EBV-transformed B
      cell lines were used to analyze immunoglobulin and Aa-specific antibody
      responses, as well as to determine the frequencies of cells producing
      immunoglobulin (Ig) of a specific isotype and detect clones secreting antibodies
      specific for Aa. Lymphoblastoid cells lines (LCL) were derived by clonal
      transformation of peripheral blood lymphocytes from 10 Aa-infected patients with
      adult periodontitis (Aa-AP) and seven normal subjects. METHODS: The B cells were
      incubated in Aa-coated polystyrene plates to separate adherent and non-adherent
      cells, and stimulate the cells with the whole bacteria. In addition, the B cells
      were stimulated with Aa LPS, E. coli LPS, or the polyclonal B cell activators
      (PBAs), pokeweed mitogen (PWM) and Staphylococcus aureus protein A (SpA). Both
      adherent and non-adherent cell populations were cultured for up to 15 days. MAIN
      OUTCOME MEASURE: Total immunoglobulins (Igs) and antibody (IgG, IgA, IgM) levels
      to Aa in the culture supernatants were assessed using an ELISA. The distribution
      of IgG, IgA, IgM and Aa-specific antibody producing cells was analyzed by a
      double immunoenzymatic staining technique. RESULTS: IgM levels produced by the
      LCLs were significantly increased vs IgG and IgA (P < 0.001). Three days after Aa
      stimulation, a marked increase in the level of total Igs and Aa-specific antibody
      was observed in adherent cells from Aa-AP (P < 0.05-0.03). Aa-specific antibody
      levels were significantly higher in the supernatants from Aa-AP vs normals
      throughout the culture interval (P < 0.03). There was also a significant increase
      in Aa-specific antibody levels after stimulation with Aa LPS or E. coli LPS (P <
      0.05), whereas PWM and SpA had no significant effect on antibody to Aa. There was
      a predominance of IgM cells compared to IgG and IgA isotypes (P < 0.04) in LCLs
      from Aa-infected patients. After stimulation with Aa, a significant increase in
      the number of IgA (111%) and IgG (48%) secreting cells was observed, concomitant
      with a 74% decrease in the Ig-negative cell population. Total Aa+ cells increased
      significantly after stimulation (P < 0.001), predominated by Aa-specific IgG and
      IgM antibody producing cells. CONCLUSIONS: These results showed that LCLs from Aa
      infected patients were polyclonal with respect to isotype distribution. Further
      stimulation with Aa revealed a shift to cytoplasmic IgG and IgA expression, as
      well as increases in the Aa-specific B cell population. In contrast, the PBAs
      stimulated the LCLs to synthesize primarily IgM. Additionally, the findings
      indicated that: (1) without T cells, polyclonal activation of B cells may lead to
      elevated Aa-specific B cell populations; and (2) the presence of previously
      sensitized B cells is required to exert an antigen specific antibody response in
      the LCL. We conclude that secondary activation of primed B cells by oral bacteria
      or their products in advanced periodontal lesions may contribute to the local
      accumulation of significant numbers of Ig-producing cells. This report also
      suggested that EBV-mediated transformation can be used to probe B cell-bacterial
      interactions in studies of periodontitis.

PMID- 9643225
TI  - Oral Submucous Fibrosis Experts Symposium held at the 5th International Congress
      on Oral Cancer. London, 26th September 1997. Abstracts.

PMID- 9643226
TI  - Toothpaste, mouthrinse and other topical remedies in periodontics.

PMID- 9643227
TI  - The history of oral hygiene products: how far have we come in 6000 years?
AB  - How far have we come in the past six millennia? Numerous dental epidemiological
      studies indicate that people are keeping their teeth longer than over before in
      this century. Agents and devices have evolved, by custom and by research, to
      enable people, with professional assistance, to maintain good oral health. Our
      diets, our lifestyles and our professional colleagues have "conspired" as
      pathogenic influences on oral health. The profession has met the challenge by
      developing and perfecting a myriad of devices and agents to thwart these
      pathogenic factors. Patient motivation and professional acceptance of preventive
      dentistry procedures still remain challenges. We certainly eat well, speak well,
      look fine and "smell fresh"--but we also have plaque, gingivitis and dental
      caries. The reader can determine how much progress has been made by reflecting on
      his or her personal oral health status!

PMID- 9643228
TI  - Is the chemical prevention of gingivitis necessary to prevent severe
      periodontitis?
AB  - Gingival inflammation seldom causes discomfort, social embarrassment or loss of
      function. As most sites with gingival inflammation do not progress to severe
      periodontal disease, gingivitis should not be considered a public health problem.
      Periodontitis is always preceded by gingivitis. But most gingivitis remains
      stable for years without progressing to periodontitis. The number of gingivitis
      sites that do convert is small. The levels of oral cleanliness achieved by the
      majority of populations in industrialized countries are below the threshold for
      severe destructive periodontal disease of personal and public health concern.
      Because methods of measuring the progression of periodontal disease are
      unreliable, definitive answers regarding conversion of gingivitis to severe
      periodontitis are lacking. Gingival inflammation frequently remains contained;
      most gingivitis remains stable for years without progressing to periodontitis.
      Decreasing gingivitis does reduce shallow pocketing, but the effect on severe
      periodontitis is not clear. Although the underlying justification for the
      reduction of plaque is to reduce gingival inflammation to prevent or reduce
      severe periodontitis and tooth loss, the basis for the approach is equivocal. A
      reasonably high level of plaque appears to be compatible with acceptably low
      levels of periodontal disease. Reducing nonspecific plaque levels to such levels
      is therefore a rational goal. The conventional methods of controlling periodontal
      disease involve mechanical removal of plaque and calculus. A complimentary
      ecological approach, using chemicals, would be to alter the environment of the
      pocket to prevent growth of putative pathogens. Any ecological approach should be
      sensitive to the dangers of disrupting the natural ecology of dental plaque. Some
      antimicrobial and antimetabolic agents such as fluoride, chlorhexidine and
      triclosan and zinc citrate can selectively suppress certain organisms or inhibit
      bacterial proteases implicated in tissue damage. The uncertainties about factors
      that convert gingival inflammation into periodontitis and periodontitis into
      severe periodontitis coupled with insufficient data from controlled clinical
      trials on the effectiveness of chemical reduction of gingivitis to prevent severe
      periodontitis leads one to conclude that more research is required before the
      need for the chemical prevention of gingivitis to prevent severe periodontitis
      can be justified.

PMID- 9643229
TI  - Controlling plaque by disrupting the process of plaque formation.

PMID- 9643230
TI  - Gum health product formulations: what is in them and why?
AB  - Two dominant factors dictate which ingredients are used in formulating toothpaste
      and mouthwashes. The major one is the type of active ingredient chosen,
      especially cationic active ingredients such as chlorhexidine; the other factor is
      the needs of the consumer. Apart from gum health benefits, the consumer expects
      to obtain from gum health toothpaste and mouthwashes other benefits of clean
      teeth (abrasive and detergent), fresh breath (antimicrobial agents and flavor)
      and protection from caries and possibly tartar. Exhaustive testing involving
      experimental design and validated laboratory and clinical tests is essential to
      ensure that all these benefits are delivered. Unless products are developed
      systematically, then products with relatively poor activity can find their way on
      to the market.

PMID- 9643231
TI  - Evaluation of oral hygiene products: science is true; don't be misled by the
      facts.
AB  - Most people in industrialized countries use oral hygiene products. When an oral
      health benefit is expected, it is important that sufficient scientific evidence
      exist to support such claims. Ideally, data should be cumulative derived from
      studies in vitro and in vivo. The data should be available to the profession for
      evaluation by publication in refereed scientific journals. Terms and phrases
      require clarification, and claims made by implication or derived by inference
      must be avoided. Similarity in products is not necessarily proof per se of
      efficacy. Studies in vitro and in vivo should follow the basic principles of
      scientific research. Studies must be ethical, avoid bias and be suitably
      controlled. A choice of controls will vary depending on whether an agent or a
      whole product is evaluated and the development stage of a formulation. Where
      appropriate, new products should be compared with products already available and
      used by the general public. Conformity with the guidelines for good clinical
      practice appears to be a useful way of validating studies and a valuable guide to
      the profession. Studies should be designed with sufficient power to detect
      statistically significant differences if these exist. However, consideration must
      be given to the clinical significance of statistically significant differences
      between formulations since these are not necessarily the same. Studies in vitro
      provide supportive data but extrapolation to clinical effect is difficult and
      even misleading, and such data should not stand alone as proof of efficacy of a
      product. Short-term studies in vivo provide useful information, particularly at
      the development stage. Ideally, however, products should be proved effective when
      used in the circumstances for which they are developed. Nevertheless, a variety
      of variable influence the outcome of home-use studies, and the influence of the
      variable cannot usually be calculated. Although rarely considered, the cost
      benefit ratio of some oral hygiene products needs to be considered.

PMID- 9643232
TI  - Clinical indications for the use of chemical adjuncts to plaque control:
      chlorhexidine formulations.

PMID- 9643233
TI  - Chlorhexidine: is it still the gold standard?
AB  - After 20 years of use by the dental profession, chlorhexidine is recognized as
      the gold standard against which other antiplaque and gingivitis agents are
      measured. Chlorhexidine's antiplaque effect is a result of the dicationic nature
      of the chlorhexidine molecule, which affords the agent the property of
      persistence of antimicrobial effect at the tooth surface, through both
      bactericidal and bacteriostatic effects. Although other antiplaque agents may
      show either purely immediate effect, or limited persistence, the degree of
      chlorhexidine's persistence of effect at the tooth surface is the basis of its
      clinical efficacy. Similarly, the cationic nature of the chlorhexidine molecule
      is the basis of the most common side effect associated with the use of the agent-
      extrinsic tooth staining. Such tooth staining seems to be the result of a local
      precipitation reaction between tooth-bound chlorhexidine and chromogens found
      within foodstuffs and beverages. The cationic nature of the chlorhexidine
      molecule also means that the activity of the agent is rapidly reduced in the
      presence of anionic agents, specifically those found within certain types of
      toothpaste; thus care is required when using normal toothbrushing alongside
      chlorhexidine. By understanding how the chemical properties of the chlorhexidine
      molecule can explain the plethora of clinical efficacy and safety data, the use
      of chlorhexidine can be optimally aimed towards the patient groups who would most
      benefit from the superior therapeutic effect of the agent. Specifically,
      chlorhexidine would seem to be of most value to patients in whom the ability to
      perform adequate oral hygiene procedures has been compromised. In these
      individuals the delivery of the correct dose of chlorhexidine to the tooth
      surface can be optimized through the judicial use of the several different
      chlorhexidine formulations now available. Thus, by understanding the properties
      and limitations of the chlorhexidine molecule, the dental profession can ensure
      that the efficacy of the agent is maximized, and the side effects associated with
      the agent are minimized, allowing chlorhexidine to rightly remain the gold
      standard against which other antiplaque agents are measured.

PMID- 9643234
TI  - Metal salts, essential oils and phenols--old or new?

PMID- 9643235
TI  - Supragingival calculus and periodontal disease.

PMID- 9643236
TI  - Vehicles: how to deliver the goods.

PMID- 9643237
TI  - Strategies and agents in supragingival chemical plaque control.

PMID- 9643238
TI  - Chemical plaque control--prevention for the masses.

PMID- 9643239
TI  - It's all in the sequence: community health.

PMID- 9643240
TI  - Esthetic single-tooth replacement with implants: a team approach.
AB  - The range of indications for implant-borne prostheses in partially edentulous
      patients has expanded in recent years as a consequence of advances in
      regenerative techniques for bone and soft tissues. The esthetic demands of both
      patients and dentists have risen in parallel with these advances. Esthetic
      compromises in prostheses have become increasingly less tolerable, particularly
      in the anterior region of the maxilla. If the presenting situation is less than
      optimal, extensive preprosthetic measures may be required to prepare local
      tissues for acceptance of esthetically and functionally adequate prostheses.
      Particularly in difficult situations, collaboration by a team is recommended. The
      exchange of ideas and experience among specialists should begin as early as the
      treatment planning stage and extend over the entire course of therapy. The
      objective should be defined and the various steps of treatment should be
      coordinated with participation from all team members.

PMID- 9643241
TI  - A retrospective look at esthetic resin composite and glass-ionomer Class III
      restorations: a 2-year clinical evaluation.
AB  - OBJECTIVE: A restorative material for Class III cavities must, besides being
      functional, be esthetically satisfactory, providing good working conditions and
      several shade and color options. A clinical evaluation was initiated to compare
      the suitability of resin composite and glass-ionomer cement materials for such
      restorations. METHOD AND MATERIALS: Forty-two Class III conservative cavities,
      esthetically important because of facial extensions, were selected. Resin
      composite restorations were placed in 21 cavities, and the remaining 21 were
      restored with glass-ionomer cement. The following characteristics were studied:
      color or esthetics, anatomic shape, surface texture, staining, marginal
      infiltration, dental plaque retention, and occurrence of fracture. After 24
      months, the restorations were evaluated. RESULTS: The only statistically
      significant difference between the resin composite and glass-ionomer cement
      restorations in the experimental period involved color or esthetics. CONCLUSION:
      Resin composites and glass-ionomer materials provide excellent functional and
      esthetic results in Class III cavities when properly indicated.

PMID- 9643242
TI  - The effect of amalgam bonding on resistance form of Class II amalgam
      restorations.
AB  - OBJECTIVE: This study evaluated the load required to produce failure in Class II
      bonded amalgam restorations. METHOD AND MATERIALS: Five groups of 12 maxillary
      molars were mounted. Class II mesio-occlusal preparations were cut: group 1,
      extension through central grooves, without retention grooves; group 2, proximal
      slot preparation, without retention grooves; groups 3 and 5, slot preparation
      with long facial and lingual retention grooves; group 4, slot preparation without
      grooves, with unsupported proximal enamel allowed to remain. Groups 1 to 4 were
      restored with an amalgam-bonding system and amalgam; in group 5, no amalgam
      bonding material was used. RESULTS: Mean (SD) failure loads: group 1, 281 (77) N;
      group 2, 246 (101) N; group 3, 238 (84) N; group 4, 254 (100) N; and group 5, 191
      (66) N. CONCLUSION: Although there was a trend toward greater resistance to
      dislodgment or fracture when an amalgam-bonding technique was used, its use did
      not significantly increase the resistance to failure when compared to retention
      grooves alone.

PMID- 9643243
TI  - A retrospective evaluation of a series of dentin-bonded ceramic crowns.
AB  - OBJECTIVE: This study assessed the clinical performance of dentin-bonded crowns,
      in which ceramic crowns are bonded to underlying dentin with a resin composite
      based luting material and a dentin bonding agent. METHOD AND MATERIALS: Twenty
      five patients who had received such restorations more than 1 year previously were
      recalled for evaluation of their crowns. RESULTS: Sixty dentin-bonded complete
      coverage restorations were assessed. Forty-one of the crowns had been placed on
      incisor teeth. The mean time since placement of the restorations was 2.43 years.
      Fifty-seven of the 60 restorations were intact. The three failures had resulted
      from cracks in the restorations, which had not clinically debonded. No secondary
      caries was detected at the crown margins, and anatomic form was assessed as
      excellent for 56 crowns. Root canal treatment had been required in one case.
      Color match was rated very good for 47 crowns. All 25 patients were satisfied
      with their restorations. CONCLUSION: Dentin-bonded crowns may be found to have a
      low rate of failure and to provide a high level of patient satisfaction.

PMID- 9643244
TI  - A comparison of three methods for detecting Candida albicans in patients with
      Sjogren's syndrome.
AB  - OBJECTIVE: An immediate chairside technique (Latex Candida) for the detection of
      Candida albicans was compared with a simple tube culturing technique (Oricult)
      and the traditional laboratory culturing technique in patients with Sjogren's
      syndrome. METHOD AND MATERIALS: Subjects with primary (n = 9) and secondary (n =
      9) Sjogren's syndrome (mean age of 56.7 years; all female) and an age- and sex
      matched group of control subjects (n = 9) were selected. Three different methods
      for culturing Candida albicans were performed for each subject. One culturette
      was plated on a trypticase soy-agar streptomycin-vancomycin medium plate and
      incubated for 48 hours at 37 degrees C. Another swab was plated on a reagent
      paper with the Latex Candida test kit. The third swab was placed in a culture
      media tube using the Oricult kit and incubated for 48 hours at 37 degrees C.
      RESULTS: All three techniques indicated a significant difference in the
      prevalence of Candida between the control group and both Sjogren's groups. The
      Latex Candida technique indicated that 78% of all Sjogren's subjects were
      positive for Candida, while the other two tests indicated that 83% were positive.
      CONCLUSION: The Latex Candida technique was comparable to Oricult and
      streptomycin-vancomycin culturing techniques for negative results and was
      correctly positive for 90% of cases.

PMID- 9643245
TI  - Use of a resin-ionomer in the treatment of mechanical root perforation: report of
      a case.
AB  - A perforated root represents a difficult challenge to the clinician, and
      treatment of such defects often involves surgical and/or advanced restorative
      techniques. This typically requires a series of lengthy, often stressful
      appointments, may compromise esthetics, and invariably involves additional costs
      to the patient. This case report describes the nonsurgical treatment of separate
      mechanical perforations that resulted from the removal of a failed prefabricated
      post. The tooth was restored in a minimum number of visits through the use of a
      novel application of a resin-ionomer material originally designed for routine
      restorative procedures.

PMID- 9643246
TI  - The effectiveness of a modified hydrochloric acid-quartz-pumice abrasion
      technique on fluorosis stains: a case report.
AB  - Endemic dental fluorosis is a form of enamel hypoplasia characterized by moderate
      to-severe staining of the tooth surface. Since 1916, numerous investigators have
      used hydrochloric acid alone on fluorosis stains. More recently, 18% hydrochloric
      acid-pumice microabrasion has been used to achieve color modification. The main
      disadvantage of this procedure is the high concentration and low viscosity of
      hydrochloric acid, which can cause damage to oral and dental tissues. To
      eliminate this problem, quartz particles can be mixed with the hydrochloric acid.
      The quartz particles prevent the hydrochloric acid from flowing uncontrollablely
      by altering it to a gel-like form. A modified 18% hydrochloric acid-quartz-pumice
      abrasion technique was used to remove fluorine stains from vital teeth in a
      teenager.

PMID- 9643247
TI  - The use of an orthodontic thermoplastic retainer as a provisional anterior
      restoration: a case report.
AB  - Children who present with extensive fractures of anterior teeth pose a difficult
      clinical problem. Pulpal and periodontal injuries must be carefully assessed and
      managed. Rapid restoration of the form and contour of the extensively fractured
      tooth is advisable, not only to improve esthetics but also to prevent unwanted
      tipping or tilting of adjacent teeth and overeruption of opposing teeth. A
      modified Essix retainer, simply constructed in the laboratory, can be used to
      provisionally restore the extensively fractured anterior tooth.

PMID- 9643248
TI  - It's all in the sequence: community health, education, and communications.

PMID- 9643249
TI  - Fabrication of an amalgam core using a customized acrylic resin shell.
AB  - This article describes a build-up technique that uses a customized acrylic resin
      shell for restoring endodontically treated molars that are involved in three-unit
      fixed partial denture design. The shell confines the amalgam without impinging on
      the periodontium to ensure a proper core foundation, an ideal tooth preparation,
      and a more predictable final restoration.

PMID- 9643250
TI  - The beginning of the end of the antibiotic era? Part I. The problem: abuse of the
      "miracle drugs".
AB  - The antibiotic era began in the early 1940s with the clinical use of penicillin.
      Subsequent discovery, development, and clinical use of other antibiotics resulted
      in effective therapy against major bacterial pathogens. These drugs were so
      effective that bacterial infectious diseases were considered by many experts to
      be under complete therapeutic control. However, the scientific community grossly
      underestimated the remarkable genetic plasticity of these organisms and their
      ability, through mutations and genetic transfer, to develop resistance to
      antibiotics. Infectious diseases are now the world's major cause of death. The
      cause of bacterial reemergence as a threat to human health and life is the abuse
      of the "miracle drugs." The ubiquitous nature of antibiotics in the human
      ecosystem foments bacterial resistance and threatens to eliminate antibiotics as
      effective drugs for human therapeutic use.

PMID- 9643251
TI  - The immediate provisional restoration: a review of clinical techniques.
AB  - For each patient who requires removal of anterior teeth, there are a multitude of
      treatment considerations. Cosmetic demands, functional needs, treatment
      sequencing, timeliness, and affordability are some primary concerns that must be
      addressed on an individual basis. A patient will generally want a cosmetic and
      functional prosthesis at the earliest possible opportunity. Providing the most
      appropriate interim prosthesis for a given patient is both challenging and
      rewarding. The numerous clinical techniques for immediate interim tooth
      replacement are reviewed, and previously unreported methods are presented to
      assist the clinician in the selection of interim prosthesis design.

PMID- 9643252
TI  - The bonded amalgam restoration: a case report.
AB  - The development of resin cements for use in fixed prostheses has suggested the
      possibility of a new direct restorative technique, the bonded amalgam. This
      restoration technique reportedly reduces microleakage and increases adhesion to
      dental structure compared to conventional amalgam restorative techniques. Factors
      such as tooth conservation, occlusion, patient age, and the time required for the
      execution of this type of restoration should also be considered. An amalgam
      restoration was placed with the adhesive technique in a 13-year-old patient with
      a nonvital mandibular left second molar and limited interocclusal space. After 3
      years of observation, the restoration shows excellent function, suggesting its
      appropriateness for special clinical situations.

PMID- 9643253
TI  - Biocompatibility of Clearfil Liner Bond 2 and Clearfil AP-X system on nonexposed
      and exposed primate teeth.
AB  - OBJECTIVE: Recent studies have demonstrated that acid etching of vital dentin and
      pulpal tissue does not retard pulpal healing, odontoblastoid cell
      differentiation, or dentinal bridge formation when the pulp is capped with
      adhesive resins. The purpose of this study was to evaluate the pulpal response in
      nonexposed and exposed monkey pulps to treatment with the Clearfil Liner Bond 2
      and Clearfil AP-X system. METHOD AND MATERIALS: Class V and Class I cavities in
      nonexposed and exposed pulps were observed at 7 or 8, 27, and 97 days. RESULTS:
      There were no differences in pulpal inflammation between the Clearfil Liner Bond
      2/Clearfil AP-X specimens and calcium hydroxide controls in either Class V or
      Class I cavities at the various time periods. CONCLUSION: Clearfil Liner Bond 2
      and Clearfil AP-X system is not toxic to either nonexposed or exposed pulpal
      tissues when placed according to manufacturer's directions.

PMID- 9643254
TI  - Management of the fractured maxillary tuberosity: an alternative method.
AB  - The maxillary tuberosity can fracture during extraction of a molar tooth. If a
      small bony fragment is affected, the extraction of the tooth and tuberosity
      continues; however, a conservative approach is advised if the bony fragment is
      large. In a modified blind surgical technique, the tooth is removed without the
      fractured bone.

PMID- 9643255
TI  - Oligodontia--a case report.
AB  - Oligodontia is defined as the congenital absence of six or more teeth, excluding
      the third molars. Genetic factors play an important role in oligodontia, which
      can occur as an isolated finding or as part of a syndrome. Characteristic dental
      symptoms are a reduced number of teeth, a reduction in tooth size, anomalies of
      tooth form, and delayed eruption. This article describes treatment of a 6-year
      old girl with congenital absence of 16 permanent teeth. Her malocclusion was
      corrected by orthodontic therapy, and removable partial dentures were made to
      improve esthetics and chewing function.

PMID- 9643256
TI  - Hand, foot, and mouth disease: a case report.
AB  - Hand, foot, and mouth disease is a viral infection related to coxsackieviruses
      A5, A6, A9, and A10, coxsackieviruses B2 and B5, and echovirus 11. It generally
      affects children, but this article presents a clinical case of a young woman with
      hand, foot, and mouth disease. Patients with this disease have oral and skin
      lesions that may be confused with other diseases. The differential diagnosis is
      very important because both dental and medical professionals may misdiagnose the
      disease and sometimes prescribe an inappropriate medication.

PMID- 9643257
TI  - An investigation of the effect of a desensitizing dentifrice on dentinal tubules
      in vitro and in vivo.
AB  - The effect of Sensodyne dentifrice, which contains strontium chloride
      hexahydrate, on the occlusion of dentinal tubules was studied in vivo and in
      vitro. Eight premolar teeth scheduled for extraction for orthodontic purposes
      were used. Four of the teeth were extracted before Sensodyne application (in
      vitro). The other four teeth were treated in vivo and then extracted. A patch of
      enamel was removed from all the teeth to expose the dentinal surfaces, and the
      smear layer over the exposed area was removed. In the in vivo test, the patients
      were instructed to brush their teeth for 1 minute, twice a day, for 2 weeks. The
      teeth were then extracted and kept in distilled water until examined by scanning
      electron microscope. The in vitro teeth were brushed in the same manner and kept
      in distilled water between brushings. Most of the in vitro dentinal tubules were
      found to be open, whereas most of the in vivo dentinal tubules were occluded.

PMID- 9643258
TI  - It's all in the sequence: practice management.

PMID- 9643259
TI  - Five-year clinical performance of porcelain veneers.
AB  - OBJECTIVE: The overall clinical performance of porcelain veneers was evaluated at
      5 years. METHOD AND MATERIALS: Porcelain veneers were placed on 87 maxillary
      anterior teeth in 25 patients (19 to 69 years) by a single operator following a
      standardized clinical procedure. At the 5-year recall, esthetics, marginal
      performance, vitality, fracture rate, and patient satisfaction were recorded.
      RESULTS: At recall, 93% of the veneers were satisfactory without intervention.
      The remaining 7% presented clinically unacceptable problems such as recurrent
      caries, porcelain fracture, severe clinical microleakage, or pulpal reaction. The
      retention rate of the porcelain veneers was 100%, and the maintenance of
      esthetics was perfect. Only 14% of the veneers presented excellent marginal
      adaptation over the entire outline of the restoration; however, the impact of the
      slight marginal defects on the clinical performance was negligible. CONCLUSION:
      Labial porcelain veneers offer a reliable and effective procedure for the
      conservative treatment of discolored, malformed, and malaligned anterior teeth.

PMID- 9643260
TI  - The beginning of the end of the antibiotic era? Part II. Proposed solutions to
      antibiotic abuse.
AB  - The bacteria causing diseases that are now becoming serious public health threats
      are neither strange nor exotic, but rather shockingly familiar. Tuberculosis,
      typhoid fever, meningitis, pneumonia, and septicemias are emerging global
      threats. The infectious agents causing these serious threats are the same
      bacteria identified many decades ago. The only difference is that these and other
      microorganisms are no longer killed by the "miracle drugs" that have kept them at
      bay for the past six decades. Antibiotic resistance has made potential killers
      out of bacteria that previously posed little threat to mankind. The
      indiscriminate and reckless use of antibiotics has led to a fast-approaching
      crisis in which human dominance of the planet is threatened by single, elementary
      cells of the microbial world. Part I of this article detailed the causes of the
      crisis. Part II addresses the solutions that are recommended by national and
      international authorities and organizations.

PMID- 9643261
TI  - Autoclave performance and practitioner knowledge of autoclave use: a survey of
      selected UK practices.
AB  - OBJECTIVE: It is essential that the dental surgery autoclave be tested regularly
      to ensure that it is operating at a temperature and pressure that will kill all
      microorganisms. The aims of this study were to investigate the knowledge of
      general dental practitioners on aspects of autoclave use, to examine their
      autoclaving routines, and to test the effectiveness of the sterilization cycle of
      their practice's autoclave. METHOD AND MATERIALS: A 35-question questionnaire was
      distributed to 840 dental practitioners in the United Kingdom. They were also
      sent three spore test ampules with details of their function and instructions on
      their use. The practitioners were asked to use the spore test ampules in their
      own practice's autoclave and to return these for testing. RESULTS: Four hundred
      one questionnaires and associated spore test ampules were returned for analysis,
      a 47.7% response rate. Eight practice autoclaves (2.0%) failed to sterilize the
      spores. These practices were offered a retest following counseling. A total of
      77.8% of respondents had received formal training in infection control. Of the
      71.3% of respondents who stated that they check the performance of their
      autoclave routinely, 31.5% use a chemical strip every cycle, 17.5% use it once
      per day, and 30.4% use it once per week. However, only five respondents (1.2%)
      use a spore test; two of these respondents use it every cycle, one once per day,
      and two once per week. CONCLUSION: Further education of practitioners may be
      necessary to enhance their awareness of the need for routine checking of
      autoclave effectiveness.

PMID- 9643262
TI  - Fenestration gingival defect in erupting permanent mandibular incisors: a case
      report.
AB  - Bilateral fenestration of the labial gingival tissue of the permanent mandibular
      central incisors is described. The situation was followed over a 2-year period
      with no treatment other than prophylaxis and oral hygiene instruction. The final
      outcome was an apical positioning of the gingival margin, which was lower than
      that of the adjacent uninvolved teeth.

PMID- 9643264
TI  - Tobacco: addiction, oral health, and cessation.

PMID- 9643263
TI  - Incomplete fractures in intact bilateral maxillary first molars: a case report.
AB  - A case of incomplete fractures occurring bilaterally in intact maxillary first
      molars is described. The etiology, diagnosis, and treatment of incomplete tooth
      fractures are discussed. The clinical results in this case showed that early
      diagnosis and treatment can prevent further extension of the crack into the pulp
      and subsequent complete tooth fracture.

PMID- 9643265
TI  - Helping patients quit smoking: lessons learned in the trenches.
AB  - Cigarette smoking is a genuine and complex addiction that involves three
      interconnecting links: the central link, nicotine (physiologic) addiction, is
      joined to two additional links, psychologic (cognitive and affective) dependence
      and sociocultural (environmental) factors. It is precisely this dynamic
      combination of related factors that makes cigarette smoking so incredibly
      resistant to long-term extinction. Successful management of highly dependent
      smokers requires that clinicians use a structured, multifaceted, patient-oriented
      approach that includes the use of nicotine replacement and nicotine withdrawal
      therapy, intensive monitoring, and long-term follow-up. In this article, the
      author offers practical advice gleaned from 30 years of practical experience and
      one-on-one contact with 400 patients who have attempted to quit smoking during
      the past 5 years at the Indiana University Nicotine Dependence Program.

PMID- 9643266
TI  - Smoking cessation.

PMID- 9643267
TI  - Tobacco cessation in the dental office: a brief intervention for spit tobacco
      users.

PMID- 9643268
TI  - Get active about passive smoking in 1998.

PMID- 9643269
TI  - Coxsackievirus genome in myocardium of patients with arrhythmogenic right
      ventricular dysplasia/cardiomyopathy.
AB  - Enteroviruses are known as major infectious agents for inflammatory heart
      diseases such as myocarditis and dilated cardiomyopathy (DCM). Arrhythmogenic
      right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by replacement
      of right ventricular myocardium by fatty and fibrous tissue. In about 65% of
      patients inflammatory infiltrates suggest an inflammatory or infectious
      etiopathogenesis. To test this hypothesis, we investigated endomyocardial
      biopsies of patients with ARVC, with myocarditis or DCM, and from patients with
      non-inflammatory cardiac disorders for the presence of enteroviral genome.
      Enteroviral RNA with homology to coxsackieviruses type B was detected in 3 of 8
      patients with ARVC (37.5%), in 7 of 23 patients with myocarditis or DCM (30.4%),
      but in none of 5 patient with non-infectious myocardial diseases (p < 0.05
      compared to ARVC patients). These results support earlier suggestions that
      coxsackievirus infection of the myocardium is possibly related to the
      pathogenesis of ARVC.

PMID- 9643270
TI  - Disrupted mobile aortic plaques are a major risk factor for systemic embolism in
      the elderly.
AB  - Protruding aortic plaques--especially those with mobile properties--on
      transesophageal echocardiography (TEE) are a potential source of stroke and
      systemic embolism in the elderly. Whether the various morphologies of atheromas
      with mobile components represent potential differences in the risk for embolic
      events has not been thoroughly elucidated. The goal of the present study was to
      determine the association between embolic events and the various types of mobile
      lesions in the thoracic aorta. Our population consisted of 569 consecutive
      patients (age 18-83 years) referred for TEE over 27 months; 108 (19%) of them
      were referred to evaluate recent embolism (cerebral in 97 and peripheral or both
      in 11; group I) and the remaining 461 were admitted for reasons unrelated to
      embolism (group II). In group I, 35 patients (32%) exhibited protruding plaques;
      those were fixed in 10 (9%) and with a mobile component in 25 (23%). In group II,
      plaques were found in only 13 patients (3%); fixed in 9 (2%) and mobile in 4 (1
      %). Twenty-four patients with mobile lesions in group I were > 50 years old, and
      21 of them (88%) were > 60 years old. While the presence of fixed plaques was
      associated with a moderate increase in the risk for systemic embolism (adjusted
      odds ratio 4.1; 95% confidence interval 1.3-56.4), mobile lesions were linked to
      a striking augmentation of this risk (odds ratio 30.1; 95% confidence interval
      7.8-132.6). The majority of mobile lesions (76%) in group I represented disrupted
      atheromas with characteristic ulcerations or echolucency within the plaque
      suggestive of intraatheroma hemorrhage, whereas these TEE features were not
      observed in 89% of the mobile lesions in group II (p = 0.0003). We conclude that
      among the various types of mobile aortic lesions, the disrupted protruding
      plaques are a major risk factor for stroke and embolic events in the elderly.

PMID- 9643271
TI  - Surgical treatment of the coronary artery to pulmonary artery fistulas in adults.
AB  - Coronary artery to pulmonary artery fistula (CA-PAF) is a rare congenital
      anomaly. The purpose of this retrospective study was to analyze 11 adult patients
      with CA-PAFs treated surgically, and to evaluate the surgical management and long
      term results. There were no surgical deaths and all patients survived the follow
      up periods (mean 7.2 years). All symptomatic patients improved their New York
      Heart Association functional class. As surgical correction is safe and effective,
      with good long-term results, all the patients with CA-PAF in adults can be
      candidates for surgery to prevent life-threatening complications.

PMID- 9643272
TI  - Assessment of functional results after percutaneous transluminal coronary
      angioplasty by cardiopulmonary exercise test.
AB  - Twenty-nine patients with documented coronary artery disease underwent
      cardiopulmonary exercise tests before and following a percutaneous transluminal
      coronary angioplasty (PTCA). The patients medication regimen and exercise
      protocols remained the same in both cases. Following PTCA, significant
      improvement (p < 0.001-0.0001) was noted in oxygen consumption (1,526.8 +/- 470.0
      vs. 1,686.2 +/- 390 ml/min), oxygen pulse (12.40 +/- 2.73 vs. 13.44 +/- 2.9
      ml/beat), oxygen pulse score (7.62 +/- 1.29 vs. 8.85 +/- 1.26 points) and in the
      ventilatory anaerobic threshold (993.1 +/- 177.6 vs. 1,089.8 +/- 150.9 ml/min)
      but not (p > 0.05) in maximal heart rate (128.7 +/- 16.9 vs. 132.0 +/- 17.2
      beats/min). Thus, a cardiopulmonary exercise test is an effective method to
      assess functional results following PTCA.

PMID- 9643273
TI  - A comparison of the effects of mibefradil and atenolol on regression of left
      ventricular hypertrophy in hypertensive patients.
AB  - OBJECTIVE: This study was designed to compare the effect of mibefradil, a
      selective T-type calcium channel antagonist, with the beta-blocker atenolol on
      regression of left ventricular (LV) hypertrophy in hypertensive patients.
      METHODS: In this multicenter, double-blind, active-controlled, randomized,
      parallel-group comparison, 66 patients with mild-to-moderate hypertension
      (sitting diastolic blood pressure, SDBP, 95-114 mm Hg) and LV mass index > 102
      g/m2 for males and > 88 g/m2 for females were randomized to an initial treatment
      with 50 mg of either mibefradil or atenolol for 4 weeks. Doses were increased to
      100 mg/day if blood pressure was not normalized to < or = 90 mm Hg, and, if
      needed, 25 mg of hydrochlorothiazide was added. Treatment continued for a total
      of 24 weeks. LV hypertrophy was assessed by echocardiography, and trough SDBP and
      adverse events were recorded. RESULTS: Treatment with mibefradil or atenolol
      resulted in decreases from baseline in LV mass index of 11.1% (p < 0.001) and
      9.1% (p < 0.001), respectively. The treatment difference (mibefradil vs.
      atenolol) was not statistically significant. Reductions in SDBP with mibefradil
      and atenolol were 14.3 and 10.7 mm Hg, respectively, again not statistically
      significant. Both drugs were well tolerated; however, overall there were more
      potentially drug-related adverse events reported with atenolol (48.5%) than with
      mibefradil (24.2%). CONCLUSIONS: The reductions in LV hypertrophy and blood
      pressure achieved with mibefradil were larger but statistically equivalent to
      those with atenolol, but a lower overall incidence of treatment-related adverse
      events was seen in the mibefradil-treated patients.

PMID- 9643274
TI  - Antihypertensive treatment in postmenopausal women: results from a prospective,
      randomized, double-blind, controlled study comparing an ACE inhibitor (moexipril)
      with a diuretic (hydrochlorothiazide).
AB  - The present study was designed to compare the safety and efficacy of the new
      angiotensin-converting enzyme inhibitor moexipril with that of
      hydrochlorothiazide (HCTZ) in postmenopausal women with mild-to-moderate
      hypertension. After a 4-week single-blind placebo period, 97 postmenopausal
      hypertensive women (42-74 years of age) with a sitting diastolic blood pressure
      (SDBP) of 95-114 mm Hg were randomized to receive either once daily moexipril 15
      mg or HCTZ 25 mg for a 12-week double-blind treatment period. At study endpoint,
      HCTZ caused significantly greater increases from baseline in serum uric acid
      levels than did moexipril (0.8 +/- 0.1 vs. 0.1 +/- 0.1 mg/dl, p < 0.01).
      Furthermore, 12-week treatment with HCTZ resulted in significant increases in
      glucose (+11.0 +/- 4.1 mg/dl) and total cholesterol/HDL ratio (+0.3 +/- 0.1
      mg/dl) and a significant decrease in HDL (-3.2 +/- 0.7 mg/dl). In contrast,
      moexipril treatment was not associated with significant changes in any metabolic
      parameter. Both drugs efficiently lowered SDBP with reductions of -10.0 +/- 1.3
      and -11.8 +/- 1.1 mm Hg in the moexipril and HCTZ group, respectively. Clinical
      adverse events were reported by a greater percentage of HCTZ patients (53%) than
      moexipril patients (40%), with headache and rhinitis as the most frequent events.
      The results indicate that moexipril was better tolerated than HCTZ in
      postmenopausal women and did not adversely affect metabolic parameters. Both
      drugs were effective in lowering blood pressure.

PMID- 9643275
TI  - Absence of a seasonal variation in myocardial infarction onset in a region
      without temperature extremes.
AB  - To evaluate whether the incidence of acute myocardial infarction (AMI) attack
      would have circadian, weekly and monthly variations in a subtropical area, 540
      consecutive patients with AMI who were admitted to our coronary care units were
      analyzed. Six-hour intervals over 24 h, daily intervals in a week (7 days) and
      monthly intervals in a year (12 months) were studied, respectively. Results
      showed that there was a circadian variation in the onset of AMI with a morning (6
      a.m. to noon) peak (34%, p < 0.01) but no secondary late evening (18-24 p.m.)
      peak. The incidence of AMI was significantly lower on Sundays (9%) than on the
      other weekdays (Monday through Saturday; p < 0.05). However, no monthly and
      seasonal variations in the incidence of AMI (no winter or summer peaks) were
      observed in this series. This study demonstrated a circadian variation in the
      onset of AMI attack with a predominant morning peak. The fewer AMI cases on
      Sundays compared to the other weekdays suggested that freedom from 'stress' or
      'work-load' on Sundays might have an important impact on this low incidence of
      AMI. Unlike the large ranges in cold or hot weather found in temperate regions,
      the warm climate of a subtropical region does not affect the frequency of AMI.

PMID- 9643276
TI  - Limitation of left ventricular hypertrophy and dysfunction by ACE inhibition
      after anterior Q-wave myocardial infarction.
AB  - To determine whether limitation of left ventricular (LV) hypertrophy with
      angiotensin-converting enzyme inhibition after myocardial infarction (MI) is
      associated with improved systolic and diastolic function, quantitative two
      dimensional echocardiograms and Doppler of 40 patients, who were randomized on
      day 3 after a first Q-wave anterior MI to receive therapy with captopril (12.5 mg
      t.i.d.) or placebo for 6 weeks, were analyzed for LV volumes (Simpson's rule) and
      mass (3D reconstruction), remodeling parameters and peak early (E) and late (A)
      transmitral flow velocities and deceleration times (DT) at 3 days, 6 weeks, 6
      months and 1 year. Compared to placebo over 1 year, captopril limited (p < 0.001)
      the increase in diastolic volume and mass, increased LV ejection fraction and
      diastolic E/A ratio, and decreased DT, the frequency of E and A reversal, infarct
      expansion and aneurysm frequency but volume/ mass ratio was unchanged. Captopril
      over the first 6 weeks after a first Q-wave anterior MI limited LV remodeling and
      hypertrophy and improved both systolic and diastolic function up to 1 year.

PMID- 9643277
TI  - Long-term effects on cardiac output and peripheral resistance in patients treated
      with enalapril after acute myocardial infarction. CONSENSUS II Multi-Echo Study
      Group. Cooperative New Scandinavian Enalapril Survival Study.
AB  - In the Cooperative New Scandinavian Enalapril Survival Study (CONSENSUS II), in
      which enalapril treatment was initiated intravenously within 24 h after acute
      myocardial infarction, there was a neutral effect on 6-month mortality, whereas a
      beneficial effect on the progression of congestive heart failure was noted. We
      studied the effect of enalapril on left ventricular systolic function in terms of
      cardiac output and mean acceleration time measured by pulsed-wave Doppler in the
      left ventricular outflow tract and peripheral resistance. Early angiotensin
      converting enzyme inhibition after acute myocardial infarction did not result in
      a general improvement of cardiac output. However, a small increase in cardiac
      output was observed in a subgroup of enalapril-treated patients with ejection
      fraction > or = 45%, probably due to a reduction in peripheral resistance in
      these patients.

PMID- 9643278
TI  - Accuracy of exercise-induced left axis QRS deviation as a specific marker of left
      anterior descending coronary artery disease.
AB  - In this prospective study, we examined the diagnostic accuracy of exercise
      induced left QRS axis deviation as a marker of LAD coronary artery stenosis. The
      mean frontal QRS axis of 66 consecutive patients with chest pain and exercise
      induced ST segment depression referred for diagnostic coronary angiography was
      analyzed and related to the angiographic findings. An exercise-induced leftward
      QRS axis deviation was found in 9/40 patients with and 0/26 patients without
      obstructive (> or = 70%) LAD disease (sensitivity 23%, specificity 100%, p =
      0.025). In 7 of the 9 patients with left axis deviation, the lesion was proximal
      to and in 2 in the region of the first septal perforator. Inclusion of patients
      with 0 degrees exercise-induced QRS axis deviation provided a more sensitive but
      less specific marker of LAD disease [sensitivity 53% (21/40), specificity 81%
      (21/26), p = 0.015]. The findings were similar in patients with single and with
      multivessel coronary artery disease. Grouping all patients in the present
      prospective and two previous retrospective studies (n = 165), the sensitivity was
      29% and specificity 100% (p < 0.0001). Exercise-induced left QRS axis deviation
      was a highly specific marker of LAD coronary artery stenosis.

PMID- 9643279
TI  - Atrial fibrillation: a delayed presentation of traumatic tricuspid valve
      incompetence.
AB  - Isolated tricuspid valve incompetence resulting from blunt thoracic injury is
      rare. The diagnosis may be challenging. Subsequent clinical course may be
      variable. Early surgical intervention rather than medical therapy has been
      suggested in selected cases. We report a case of blunt chest trauma causing
      delayed chronic tricuspid regurgitation manifesting primarily as atrial
      fibrillation many years after the initial blunt chest trauma. Replacement of
      tricuspid valve restored normal sinus rhythm.

PMID- 9643280
TI  - Behcet's disease ('Silk Route disease') and mitral valve prolapse.

PMID- 9643281
TI  - Medical genetics in the UK and the National Health Service.

PMID- 9643282
TI  - "Code of practice and guidance on human genetic testing services supplied direct
      to the public". Advisory Committee on Genetic Testing.

PMID- 9643283
TI  - A population study of mutations and LOH at breast cancer gene loci in tumours
      from sister pairs: two recurrent mutations seem to account for all BRCA1/BRCA2
      linked breast cancer in Iceland.
AB  - The majority of breast cancer in high risk families is believed to result from a
      mutation in either of two genes named BRCA1 and BRCA2. A germline defect in
      either gene is usually followed by chromosomal deletion of the normal allele in
      the tumour. In Iceland two recurrent mutations have been identified, 999del5
      BRCA2 and G5193A BRCA1. In this study, randomly selected pairs of sisters
      diagnosed with breast cancer at the age of 60 years or younger were analysed to
      evaluate the proportion of breast cancer resulting from BRCA1 and BRCA2.
      Genotypes and allele loss in tumour tissue from 42 sister pairs were compared
      using markers within and around the BRCA1 and BRCA2 genes. Eleven sister pairs
      were highly suggestive of BRCA2 linkage, and no obvious BRCA1 linkage was seen.
      Screening for the G5193A BRCA1 and 999del5 BRCA2 mutations showed the 999del5
      mutation in the 11 BRCA2 suggestive pairs plus three pairs less indicative of
      linkage, and the G5193A BRCA1 mutation in one pair. When known mutation carriers
      are removed from the group, no indication of further linkage to BRCA1 or BRCA2 is
      seen. The results of our studies suggest that a large proportion of familial
      breast cancer in Iceland is the result of the 999del5 BRCA2 mutation, and it is
      unlikely that BRCA1 and BRCA2 germline mutations other than 999del5 and G5193A
      play a significant role in hereditary breast cancer in Iceland. Furthermore it
      can be concluded that most families with BRCA1 or BRCA2 linkage are easily
      identified by studying LOH around the defective gene in as few as two affected
      relatives.

PMID- 9643284
TI  - Genotype/phenotype correlations in type 2 neurofibromatosis (NF2): evidence for
      more severe disease associated with truncating mutations.
AB  - Blood samples from 125 unrelated families with classical type 2 neurofibromatosis
      (NF2) with bilateral vestibular schwannomas have been analysed for mutations in
      the NF2 gene. A further 17 families fulfilling modified criteria for NF2 have
      also been analysed. Causative mutations have been identified in 54 (43%)
      classical families and six (35%) of those fulfilling modified criteria. Forty-two
      cases from 38 families with truncating mutations had an average age at onset of
      symptoms of 19 years and diagnosis at 22.4 years. Fifty-one cases from 16
      families with splice site mutations (15 from six), missense mutations (18 from
      six), and large deletions (18 from five) had an average age of onset of 27.8
      years and at diagnosis of 33.4 years. Subjects with truncating mutations were
      significantly more likely to have symptoms before 20 years of age (p<0.001) and
      to develop at least two symptomatic CNS tumours in addition to vestibular
      schwannoma before 30 years (p<0.001). There were also significantly fewer
      multigenerational families with truncating mutations. Four further truncating
      mutations were in mosaic form and were associated with milder disease than other
      similar mutations. This large study has confirmed the previous impression that
      truncating mutations are associated with severe disease, but caution has to be
      exercised in using mutation type to predict disease course.

PMID- 9643285
TI  - A silent mutation, C924T (G308G), in the L1CAM gene results in X linked
      hydrocephalus (HSAS).
AB  - The L1 cell adhesion molecule (L1CAM) is a neuronal gene involved in the
      development of the nervous system. Mutations in L1CAM are known to cause several
      clinically overlapping X linked mental retardation conditions: X linked
      hydrocephalus (HSAS), MASA syndrome (mental retardation, aphasia, shuffling gait,
      adducted thumbs), spastic paraplegia type I (SPG1), and X linked agenesis of the
      corpus callosum (ACC). In an analysis of a family with HSAS, we identified a C-
      >T transition (C924T) in exon 8 that was initially thought to have no effect on
      the protein sequence as the alteration affected the third base of a codon
      (G308G). Extensive analysis of the other 27 exons showed no other alteration. A
      review of the sequence surrounding position 924 indicated that the C-->T
      transition created a potential 5' splice site consensus sequence, which would
      result in an in frame deletion of 69 bp from exon 8 and 23 amino acids of the
      L1CAM protein. RT-PCR of the RNA from an affected male fetus and subsequent
      sequence analysis confirmed the use of the new splice site. This is the first
      report of a silent nucleotide substitution in L1CAM giving rise to an alteration
      at the protein level. Furthermore, it shows that as mutation analysis plays an
      ever more important role in human genetics, the identification of a synonymous
      base change should not be routinely discounted as a neutral polymorphism.

PMID- 9643286
TI  - A polymorphism of the CC16 gene is associated with an increased risk of asthma.
AB  - Several quantitative traits associated with the asthma phenotype have been linked
      to markers on chromosome 11q13, although the gene responsible has yet to be well
      established. The gene for Clara cell secretory protein (CC16) is an ideal
      candidate for involvement in an inherited predisposition to asthma because of its
      chromosomal location, the role of the CC16 protein in controlling airway
      inflammation, and differences in levels of the protein between asthmatics and
      healthy controls. All three CC16 exons were screened in an unselected population
      of 266 subjects from 76 families and a cohort of 52 severely asthmatic children.
      A combination of single strand conformational polymorphism (SSCP) analysis,
      heteroduplex analysis, DNA sequencing, and restriction digestion was used.
      Mutation detection methods identified an adenine to guanine substitution in the
      CC16 gene at position 38 (A38G) downstream from the transcription initiation site
      within the non-coding region of exon 1. In the unselected population, 43.6% were
      homozygous for the polymorphic sequence (38GG) and 46.2% were heterozygous
      (38AG). All the asthmatic and unaffected children from both populations were
      selected for an unmatched case control analysis consisting of 67 asthmatic and 46
      unaffected subjects. Those homozygous for the published sequence (38AA) had a 6.9
      fold increased risk of developing asthma (p=0.049) and heterozygotes (38AG) a 4.2
      fold increased risk (p=0.028). Modelling of genotype as a continuous covariate
      indicated evidence of a significant linear trend across the three genotypes (odds
      ratio=2.84 per unit increase in genotype code, p=0.018). These associations were
      independent of age, gender, and tobacco smoke exposure. These data and the known
      anti-inflammatory role of CC16 in the respiratory tract suggest that alteration
      to the gene at position 38 may contribute to asthma.

PMID- 9643287
TI  - Constitutional and mosaic large NF1 gene deletions in neurofibromatosis type 1.
AB  - A set of neurofibromatosis type 1 (NF1) patients was screened for large NF1 gene
      deletions by comparing patient and parent genotypes at 10 intragenic polymorphic
      loci. Of 67 patient/parent sets (47 new mutation patients and 20 familial cases),
      five (7.5%) showed loss of heterozygosity (LOH), indicative of NF1 gene deletion.
      These five patients did not have severe NF1 manifestations, mental retardation,
      or dysmorphic features, in contrast to previous reports of large NF1 deletions.
      All five deletions were de novo and occurred on the maternal chromosome. However,
      two patients showed partial LOH, consistent with somatic mosaicism for the
      deletion, suggesting that mosaicism may be more frequent in NF1 than previously
      recognised (and may have bearing on clinical severity). We suggest that large NF1
      deletions (1) are not always associated with unusual clinical features, (2) tend
      to occur more frequently on maternal alleles, and (3) are an important mechanism
      for constitutional and somatic mutations in NF1 patients.

PMID- 9643288
TI  - A rapid, PCR based test for differential molecular diagnosis of Prader-Willi and
      Angelman syndromes.
AB  - Approximately 98% of Prader-Willi syndrome (PWS) and 80% of Angelman syndrome
      (AS) cases have deletions at a common region in chromosome 15q11-13, uniparental
      disomy for chromosomes 15 (UPD15), or mutations affecting gene expression in this
      region. The resulting clinical phenotype (PWS or AS) in each class of mutation
      depends upon the parent of origin. Both disorders are characterised at the
      molecular level by abnormal methylation of imprinted genes at 15q11-q13 including
      the small nuclear ribonucleoprotein N gene (SNRPN). Current diagnostic strategies
      include high resolution cytogenetics, fluorescence in situ hybridisation (FISH),
      Southern blot hybridisation, or microsatellite typing. We have developed a novel
      and rapid diagnostic test for PWS and AS based on differential digestion of
      expressed (paternally imprinted) SNRPN sequences by the methylation sensitive
      endonuclease NotI or repressed (maternally imprinted) SNRPN sequences by the
      methylation requiring nuclease McrBC, followed by PCR amplification of the SNRPN
      promoter. We have evaluated this test by blinded analysis of 60 characterised DNA
      samples (20 PWS, 20 AS, and 20 unaffected controls). SNRPN sequences could not be
      amplified from PWS patient DNA which had been digested with McrBC, nor from AS
      patient DNA which had been digested with NotI. We were able to make a correct
      diagnosis of PWS, AS, or unaffected in all 60 samples tested. This novel test is
      rapid and has a high specificity and sensitivity for deletion and UPD15 cases.
      These features make this new test suitable as the initial step in a molecular
      diagnostic strategy for PWS/AS.

PMID- 9643289
TI  - A survey of phenotypic features in juvenile polyposis.
AB  - Solitary juvenile polyps are quite frequent in children, but juvenile polyposis
      (JP) is a rare autosomal dominant trait characterised by the occurrence of
      numerous polyps in the gastrointestinal tract. Extracolonic phenotypic
      abnormalities are well documented in patients with familial adenomatous polyposis
      and Peutz-Jeghers syndrome and can allow a clinical diagnosis to be made before
      the bowel pathology becomes available. Though described, characteristic
      extracolonic abnormalities have not been clearly defined in juvenile polyposis.
      We sought to determine whether there are consistent extracolonic phenotypic
      abnormalities in JP patients and how frequently this would allow diagnosis of one
      of the genetic syndromes known to be associated with juvenile polyposis. Twenty
      two JP patients underwent clinical examination and data from one patient were
      obtained from case notes. Those consenting to further investigations had x rays
      of the skull, chest, and hands and an echocardiogram if clinically indicated.
      Significant extracolonic phenotypic abnormalities were present in 18 patients (14
      male and four female), and included dermatological (13), skeletal (16),
      neurological (5), cardiopulmonary (4), gastrointestinal (3), genitourinary (4),
      and ocular (1) features. In five patients the diagnosis of a genetic syndrome was
      possible: two had Bannayan-Riley-Ruvalcaba syndrome, two had Gorlin syndrome, and
      one had hereditary haemorrhagic telangiectasia (HHT, also known as Osler-Rendu
      Weber syndrome). Other patients had some features of these conditions and of
      Cowden and Simpson-Golabi-Behmel syndromes, but these were not sufficient to
      allow a definitive diagnosis.

PMID- 9643290
TI  - Maternal age specific risk rate estimates for Down syndrome among live births in
      whites and other races from Ohio and metropolitan Atlanta, 1970-1989.
AB  - Our primary objective was to estimate, by one year and five year intervals,
      maternal age specific risk rates for Down syndrome among whites and among other
      races from two different populations, metropolitan Atlanta and south west Ohio,
      using live birth and prenatally diagnosed cases ascertained during 1970-1989. The
      five year estimates were also calculated separately for each of the five four
      year periods during these 20 years. Additionally, we compared two different
      methods of estimating these risk rates by using a third population of whites, and
      compared two different statistical methods of smoothing the risk rates. The
      results indicate good agreement between the metropolitan Atlanta and south west
      Ohio estimates within races, but show a statistically significant difference
      between the two race categories. Because 86% of live births in the "other races"
      category in the combined population are to blacks, these data may be seen as the
      first estimates of maternal age specific risk rates for Down syndrome among
      blacks calculated by one year intervals. We found excellent agreement in the risk
      rate estimates among the five four year time periods, between the estimates
      obtained by using the two different methods of estimation, and between the
      estimates obtained using the two different methods of statistical smoothing. Our
      estimated risk rates for white women in their 20s strongly reinforce those from
      previous studies currently being used for genetic counselling purposes. While we
      did find somewhat higher rates for women under 20, and increasingly higher rates
      for those over 30 years of age, these differences are not substantial. Thus, this
      study in general supports the risk rates estimated from data collected mostly
      during the 1960s and 1970s.

PMID- 9643291
TI  - Duplication of 8p23.1: a cytogenetic anomaly with no established clinical
      significance.
AB  - We present seven families with a cytogenetic duplication of the short arm of
      chromosome 8 at band 8p23.1. The duplication has been transmitted from parents to
      offspring in four of the seven families. In three families, the source of the
      extra material and its euchromatic origin were established using FISH with a YAC
      which was mapped to 8p23.1 and a whole chromosome paint for chromosome 8. FISH
      signals from this YAC were significantly larger on the duplicated chromosome
      compared with the normal chromosome in all six family members tested. Comparative
      genomic hybridisation (CGH) on a representative subject was consistent with these
      results. The families were ascertained for a variety of mostly incidental reasons
      including prenatal diagnosis for advanced maternal age. The transmission of this
      duplication by multiple phenotypically normal family members with no history of
      reproductive loss suggests the existence of a novel class of 8p23.1 duplications,
      which can be regarded as euchromatic variants or duplications with no phenotypic
      effect.

PMID- 9643292
TI  - Meckel syndrome.
AB  - Meckel syndrome (MKS) is a lethal syndrome with a central nervous system
      malformation, usually occipital meningoencephalocele, bilaterally large
      multicystic kidneys with fibrotic changes of the liver, and polydactyly in most
      cases. Additional anomalies are frequent. A common characteristic of the
      parenchymal changes of many organs is a proliferation of the stromal connective
      tissue and increase and dilatation of the associated epithelial ducts. Autosomal
      recessive inheritance is well confirmed and the gene locus has been mapped to
      chromosome 17q21-24 by genome wide linkage study. The locus was later refined to
      within a less than 1 cM region (17q22), in which most of the Finnish MKS patients
      share a common chromosomal haplotype suggesting one major and relatively old
      mutation. However, in most of the non-Finnish MKS families studied, this linkage
      could not be confirmed. The linkage studies provide evidence that more than one
      locus is involved in bringing about the combination of CNS malformations, cystic
      kidneys, and polydactyly, maybe even in typical cases of MKS. Prenatal diagnosis
      of MKS by vaginal ultrasound scan is possible from 11-12 weeks of pregnancy,
      especially in families where there is a known risk. In those families where
      linkage to 17q22 is established, prenatal diagnosis by DNA analysis is possible.

PMID- 9643293
TI  - Linkage and association of an interleukin 4 gene polymorphism with atopic
      dermatitis in Japanese families.
AB  - We examined linkage between markers at and near the IL4 gene and atopic
      dermatitis (AD) in 88 Japanese nuclear families. Affected sib pair analysis
      suggested linkage between the IL4 gene and AD (SPLINK lod=2.28). Transmission
      disequilibrium testing showed a significantly preferential transmission to AD
      offspring of the T allele of the -590C/T polymorphism of the IL4 gene (p=0.001).
      A case-control comparison suggested a genotypic association of the TT genotype
      with AD (odds ratio=1.88, p=0.01). Since the T allele was reported to be
      associated with increased IL4 gene promoter activity compared with the C allele,
      our data indicate that genetic differences in transcriptional activity of the IL4
      gene influence AD predisposition, particularly in Japanese, because of a high
      frequency of the T allele.

PMID- 9643294
TI  - A lethal skeletal dysplasia with features of chondrodysplasia punctata and
      osteogenesis imperfecta: an example of Astley-Kendall dysplasia. Further
      delineation of a rare genetic disorder.
AB  - An unusual osteochondrodysplasia presenting with lethal neonatal short limbed
      dwarfism, defective ossification, and punctate calcification within cartilage is
      presented. The features resemble four cases previously described with Astley
      Kendall dysplasia.

PMID- 9643295
TI  - Oto-onycho-peroneal syndrome: confirmation of a syndrome.
AB  - We report two sibs with a similar syndrome of abnormal external ears, peculiar
      facial features, nail hypoplasia, a bilateral fibrous fusion of the outer third
      of the clavicle and the scapular spine, and the absence of a normal
      acromioclavicular joint. The present patients represent the fourth and fifth
      cases of the oto-onycho-peroneal syndrome (MIM 259780).

PMID- 9643296
TI  - The diagnosis of Liddle syndrome by identification of a mutation in the beta
      subunit of the epithelial sodium channel.
AB  - Hypertension is a common multifactorial disorder associated with considerable
      morbidity and mortality. The kidney plays a major role in the long term
      regulation of blood pressure. Liddle syndrome (pseudo-hyperaldosteronism) is one
      of a number of monogenic disorders of salt and water transport. In a kindred with
      at least four affected members suffering from Liddle syndrome, we confirmed by
      direct DNA sequencing the identity of a novel heterozygous mutation in h
      betaENaC, the gene encoding the beta subunit of the amiloride sensitive
      epithelial sodium channel which is expressed in the distal nephron. Single
      stranded conformational polymorphism analysis showed cosegregation of the mutant
      allele within the kindred with the Liddle phenotype. An insertion of an
      additional cytosine into a string of six located between codons 593 and 595
      results in a sequence frameshift and is predicted to produce a protein truncated
      by 34 amino acids. The availability of a molecular diagnostic tool has
      implications for the management of hypertension and genetic counselling in
      families with Liddle syndrome.

PMID- 9643297
TI  - New lethal disease involving type I and III collagen defect resembling geroderma
      osteodysplastica, De Barsy syndrome, and Ehlers-Danlos syndrome IV.
AB  - We describe the clinical findings and biochemical features of a male child
      suffering from a so far undescribed lethal connective tissue disorder
      characterised by extreme hypermobility of the joints, lax skin, cataracts, severe
      growth retardation, and insufficient production of type I and type III
      procollagens. His features are compared with Ehlers-Danlos type IV, De Barsy
      syndrome, and geroderma osteodysplastica, as these disorders show some symptoms
      and signs shared with our patient. The child died because of failure of the
      connective tissue structures joining the skull and the spine, leading to
      progressive spinal stenosis. The aortic valve was translucent and insufficient.
      The clinical symptoms and signs, together with histological findings, suggested a
      collagen defect. Studies on both skin fibroblast cultures and the patient's serum
      showed reduced synthesis of collagen types I and III at the protein and RNA
      levels. The sizes of the mRNAs and newly synthesised proteins were normal,
      excluding gross structural abnormalities. These findings are not in accordance
      with any other collagen defect characterised so far.

PMID- 9643299
TI  - Laws regarding insurance companies.

PMID- 9643298
TI  - Three patients with a 45,X/46,X,psu dic(Xp) karyotype.
AB  - Few cases of isochromosomes for the short arm of the X have been reported and all
      are dicentric with variable portions of the long arms interposed between the two
      centromeres. This paper reports three cases of complete short arm duplication of
      one X chromosome in unrelated female patients. All patients also have a 45,X cell
      line and present with some characteristic features of Turner syndrome. We used
      conventional cytogenetics, in situ hybridisation, and molecular genetics to
      describe all three structurally abnormal chromosomes and the parental origin of
      two of them. We briefly discuss the "inactivation enhancement" theory; however,
      any genotype-phenotype correlation is complicated by the presence of the 45,X
      cell line.

PMID- 9643300
TI  - Microsatellite markers for the cone-rod retinal dystrophy gene, CRX, on 19q13.3.

PMID- 9643301
TI  - Neonatal hearing screening: a step towards better services for children and
      families.

PMID- 9643302
TI  - Categories of auditory performance: inter-user reliability.
AB  - Categories of Auditory Performance (CAP) describes a scale used to rate outcomes
      from paediatric cochlear implantation in everyday life. It differs from more
      technical measures by being readily applied and easily understood by non
      specialist professionals and by parents. Being based on subjective assessments,
      there is a need to establish whether ratings by different persons are comparable.
      Therefore, an analysis of inter-user reliability was undertaken using ratings
      from 23 children followed up at various intervals after implantation. Analysis
      relating scores by local teachers of the deaf and the teachers of the deaf at the
      implant centre revealed very high inter-user reliability (correlation coefficient
      0.97). This result establishes the reliability of CAP as an outcome measure for
      use in cochlear implant programmes.

PMID- 9643303
TI  - Otitis media with effusion and size at birth.
AB  - To investigate whether recurrent or persistent otitis media with effusion (OME)
      was associated with particular patterns of fetal growth, we conducted a case
      control study of 129 children admitted for insertion of grommets and 150
      controls. The risk of OME was not statistically significantly related to
      gestational age or individual measures of size at birth, but the ratio of head
      circumference to total length and the ponderal index at birth were statistically
      significantly lower in children with OME, both before and after adjustment for
      the potentially confounding effects of sex, age at current operation, and
      maternal gravidity. Mothers of cases were 2.2 times more likely than those of
      controls to have had one or more previous pregnancies that had not ended in a
      live birth (95% CI 1.3-3.8). We conclude that fetal growth, reflected by
      proportions at birth, may affect later risk of recurrent and persistent OME.

PMID- 9643304
TI  - Avoidable late diagnosis of significant sensorineural hearing loss: implications
      for practice.
AB  - The records for all children from a five-year birth cohort in the geographically
      defined area of Lothian who were referred by their health visitor to a
      centralized second tier audiology service after they failed their 7-9 month
      infant distraction hearing screen were reviewed. The sensitivities,
      specificities, positive predictive values and yield of this screen for the
      detection of significant sensorineural hearing loss > or =40 dBA requiring aiding
      and for a conductive loss persisting beyond one month over 30 dBA were
      determined. In addition, the records were studied for the same five-year birth
      cohort for children presenting to the centralized multidisciplinary third tier
      clinic with a significant sensorineural hearing loss requiring aiding, and the
      reasons for late diagnosis were determined. If high risk neonatal screening had
      been available for this population then potentially 67.5% (27 out of 40) of cases
      could have been identified by an appropriate age. Elimination of health visitor
      distraction screen false negatives for cases with loses over 60 dBA would
      potentially increase the case identification by the appropriate age to 45% (1 8
      out of 40). Thus, there is greater scope for improving our present results with
      the introduction of high risk neonatal screening than by improvements in the
      health visitor screen.

PMID- 9643305
TI  - Maternal anxiety and attitudes to universal neonatal hearing screening.
AB  - Neonatal hearing screening of all babies within the maternity unit is now
      feasible using transient evoked otoacoustic emission (TEOAE) recording. However,
      in many maternity units in the United Kingdom, the majority of babies are
      discharged within the first 48 hours. During the first two days of life, there is
      a higher proportion of babies in whom emissions cannot be recorded. A universal
      TEOAE hearing screen has been implemented in Whipps Cross Hospital. As 70% of the
      babies are discharged from the maternity unit before they are 48 hours old, a two
      stage screen was implemented, with failure at the initial TEOAE test being
      followed by a retest after 4-6 weeks. The maternal anxiety caused by this model
      was investigated in 288 mothers enrolled for the initial TEOAE test. Generally,
      anxiety was low and attitudes towards the screen were positive. Ninety-seven per
      cent of mothers considered the screen to be worthwhile at the initial test with
      15% feeling it had caused some anxiety but less than 1% being very worried. The
      mothers who had some anxieties were not dissatisfied with the screen, and within
      this group there was no increase in the proportion of babies who had failed the
      initial test. At the retest, two of 57 mothers (3.5%) considered they were very
      worried, but there was no significant deterioration in attitude towards the
      screen. Spielberger's State-Trait Anxiety Inventory revealed no significant
      difference in the anxiety state of the retest group when compared with a control
      group whose babies had not received a neonatal hearing test. The results of the
      initial test and the retest did not influence the anxiety state of the mothers.
      Ways of minimizing anxiety caused to a minority of mothers whilst maintaining
      positive attitudes to the screen are discussed.

PMID- 9643306
TI  - Evaluating noise induced hearing loss with distortion product otoacoustic
      emissions.
AB  - This study assessed the clinical efficacy of screening for noise induced hearing
      loss (NIHL) with distortion product otoacoustic emissions (DPOAE). DPOAEs were
      recorded from 76 military personnel (137 ears) aged between 17 and 41 years in
      response to equilevel 70 dB SPL primary stimulating tones. The 2f1-f2 DPOAE
      levels were correlated with audiometric thresholds at frequencies close to f2.
      Ears with normal audiograms, but with a history of military noise exposure, had
      DPOAEs that were significantly decreased in amplitude as compared to the ears of
      normal hearing non-exposed to noise subjects. These ears also had an increased
      absence of DPOAEs as compared with the ears of the normal hearing non-exposed to
      noise subjects. Although, in general, the DPOAE amplitudes and spectral frequency
      ranges reflected the audiometric NIHL configurations, in a number of cases DPOAEs
      were present for hearing losses up to 75 dB HL. As a consequence, DPOAEs
      correlated moderately and negatively with the audiometric thresholds. Applying
      test criteria designed to logically reflect NIHL, DPOAE sensitivity and
      specificity levels ranged between 0.51-0.90 and 0.63-0.25, respectively. These
      findings indicate that DPOAEs, recorded and analysed as described, are not
      sufficiently sensitive to serve as a single test to identify NIHL.

PMID- 9643307
TI  - The effect of gentamicin and furosemide given in combination on cochlear
      potentials in the guinea pig.
AB  - Single doses of gentamicin and furosemide given in combination result in a rapid
      and profound loss of cochlear function. In this study, measurement of three gross
      cochlear potentials (cochlear microphonics, compound action potentials and the
      endocochlear potential) were carried out in order to determine the ototoxic sites
      of action of the drugs given in combination. The rapidity and severity of the
      cochlear deficit is dose dependent and with the doses employed in this study (80
      mg/kg gentamicin i.v. 80 mg/kg furosemide i.v.), complete loss of cochlear
      function is seen after about 72 hours. Twenty-four hours after i.v.
      administration of the drugs, significant increases in compound action potential
      thresholds between 6 and 32 kHz were seen. In contrast, over this frequency range
      the generation of cochlear microphonics in response to stimulus levels of 70 dB
      SPL appeared to be unaffected. The endocochlear potential remained unaffected at
      24 and 72 hours after administration. These findings are taken as evidence that
      the primary site of ototoxic action of the two drugs in combination may be at the
      level of the inner hair cells and/or the afferent synapse.

PMID- 9643308
TI  - Feasibility of otoacoustic emissions as a hearing screen following grommet
      insertion.
AB  - Following grommet insertion, it is important to establish that there is no
      underlying sensorineural hearing impairment. In this hospital, approximately 1000
      grommet insertions are performed each year, thus generating a heavy workload of
      review appointments for ENT and audiology. The present study investigates the
      efficacy of performing evoked otoacoustic emissions screening on 108 children
      when they were ready to leave the hospital following grommet insertion. Bilateral
      normal otoacoustic emissions were recorded in 32% (35 children), although 99%
      (105) of the 106 children attending the outpatient review appointment had normal
      hearing sensitivity. If normal hearing thresholds were established immediately
      following surgery, it can be argued that this obviates the need for an outpatient
      review appointment; however, in this study only one-third of children could be
      discharged after surgery. Otoacoustic emissions therefore does not represent an
      effective screen at this stage.

PMID- 9643309
TI  - Cytokines: clues to the pathogenesis of SLE.

PMID- 9643310
TI  - Interleukin-2 and systemic lupus erythematosus--fifteen years later.
AB  - Systemic lupus erythematosus (SLE) is a highly heterogeneous disorder in which
      multiple immunologic abnormalities have been described. In this review, we
      thoroughly analyse the impaired T cell production of, and response to,
      interleukin-2 (IL-2) characteristic of patients with SLE. Since it was first
      reported, several articles have provided us with enlightening, but somewhat
      confusing, data that reveal the complexity of the subject. The IL-2 production by
      T cells is part of a complex network in which a discrete alteration is capable of
      disrupting the whole system. On the other hand, regulatory mechanisms exist that,
      in an attempt to compensate the primary alteration, provoke secondary defects.
      Evidence indicates that this defect is not intrinsic, but rather, results from
      multiple microenvironmental influences that act on the T cell and modify its
      activation state and its cytokine production. Abnormalities in co-stimulatory
      mechanisms and in cytokines that may be related to the IL-2 production
      deficiency, have been described in patients with SLE. We also consider the
      information derived from murine SLE models, IL-2 knockout models and reports
      concerning the immune dysregulation present in patients with SLE.

PMID- 9643311
TI  - DNAse treatment does not improve the survival of lupus prone (NZB x NZW)F1 mice.
AB  - OBJECTIVE: To examine the efficacy of deoxyribonuclease I (DNAse) therapy in the
      (NZB x NZW)F1 murine model of lupus. METHODS: Lupus-prone female (NZB x NZW)F1
      mice were treated daily with 0-15 microg/g of recombinant DNAse for 1-6 months.
      Parameters including anti-DNA autoantibody production, activation of cytokine
      secreting cells, kidney function and longevity were monitored. RESULTS: DNAse
      treatment selectively reduced the number of B cells secreting anti-dsDNA
      antibodies for approximately one month. However, neither short-term nor long-term
      treatment altered cytokine production, delayed the onset or reduced the severity
      of glomerulonephritis, or prolonged survival. CONCLUSION: DNAse treatment
      initiated before, during, or after the onset of murine lupus did not improve
      clinical outcome.

PMID- 9643312
TI  - Systemic lupus erythematosus VII: frequency and impact of secondary Sjogren's
      syndrome.
AB  - BACKGROUND: The prognosis of patients with systemic lupus erythematosus (SLE)
      largely depends on the severity of cumulative organ damage during the course of
      the disease. While Sjogren's syndrome (SS) predominantly affects exocrine glands,
      a considerable number of patients develop visceral organ damage. Thus, the
      occurrence of a secondary SS (2(o)SS) in SLE patients, may result in more
      extensive organ damage and thereby adversely affect prognosis. PATIENTS/METHODS:
      138 patients meeting the 1982 American College of Rheumatology (ACR)
      classification criteria for SLE were prospectively studied over a mean period of
      ninety months. 2(o)SS was diagnosed according to the 1993 European Study Group
      criteria and complication rates and prognosis were compared between patients with
      and without SS. RESULTS: 27 patients (19%) developed SS after a mean period of 48
      months. There was a gradual increase in SS prevalence over time after SLE-onset.
      2(o)SS patients were older (mean age 41 vs 35 years, P = 0.03), had less renal
      disease (19% vs 38%, P = 0.04), more thrombocytopenia (26% vs 9%, P = 0.05) and
      similar serological profiles (including anti-SSa) as patients without SS. Overall
      mortality was lower in patients with SS (4% vs 13.5%, P = 0.01), while lifetable
      analysis showed improved survival estimates for 2 SS patients with borderline
      statistical significance (P = 0.06). CONCLUSIONS: 2(o)SS develops in about one
      fifth of SLE patients in a time-dependent fashion: these patients are older, have
      less renal involvement and their prognosis is at least as good as for those
      remaining free of SS.

PMID- 9643313
TI  - About systemic lupus erythematosus and thrombotic thrombocytopenic purpura.

PMID- 9643314
TI  - Polyarteritis nodosa, microscopic polyangiitis and Churg-Strauss syndrome.
AB  - Polyarteritis nodosa (PAN), first described by Kussmaul and Maier, is a well
      known form of necrotizing angiitis whose manifestations are weight loss, fever,
      asthenia, peripheral neuropathy, renal involvement, musculoskeletal and cutaneous
      manifestations, hypertension, gastrointestinal tract involvement, and cardiac
      failure. Recently individualized from PAN, microscopic polyangiitis (MPA) is a
      systemic vasculitis of small-size vessels whose clinical manifestations are very
      similar to those of PAN, but it is characterized by the presence of rapidly
      progressive glomerulonephritis (RPGN), which is nearly constant, and pulmonary
      involvement usually absent in PAN. Churg Strauss syndrome (CSS) is a disorder
      characterized by hypereosinophilia and systemic vasculitis similar to that of PAN
      and occurring in individuals with asthma and allergic rhinitis. Considering the
      etiologies of PAN, primary and secondary vasculitides can also be distinguished
      because PAN can be the consequence of hepatitis B virus (HBV) infection and
      sometimes of other etiologic agents. The prognosis of systemic vasculitides has
      been transformed by corticosteroids that are, except in HBV-related PAN, the
      basic treatment. Immunosuppressive drugs, especially cyclophophamide, have also
      contributed to improving the prognosis, but their precise role in the management
      of these vasculitides is still being elucidated.

PMID- 9643315
TI  - Childhood vasculitis.
AB  - Vasculitis can and does occur in childhood. Apart from the relatively common
      vasculitides (Henoch-Schonlein purpura, Kawasaki disease and in world wide terms
      Takayasu disease) there are a number of important but comparatively rare
      disorders affecting children. These include macroscopic and microscopic
      polyarteritis, cutaneous polyarteritis, Wegener's granulomatosis, Churg-Strauss
      syndrome, primary angiitis of the central nervous system, hypersensitivity
      angiitis, hypocomplimentaemic urticarial vasculitis, vasculitis associated with
      various connective tissue disorders and vasculitis associated with conditions
      such as Behcets syndrome, familial Mediterranean fever and Cogan's syndrome.
      Distinguishing these conditions from other disorders is often difficult and
      requires clinical acumen and appropriate investigative procedures. With modern
      therapeutic agents, it is possible to implement appropriate therapy but in spite
      of this, there remains a not inconsequential morbidity and mortality.

PMID- 9643316
TI  - Giant cell arteritis.
AB  - In many populations giant cell arteritis (GCA) is the most common form of
      vasculitis. Genetic markers, ethnic factors, and increasing age over 50 years
      appear to enhance susceptibility and an infection may trigger its onset. Recent
      investigations provide evidence that the vasculitic reaction is part of an immune
      response to an antigen residing in involved artery walls. These studies along
      with the description of an experimental model of the disease have significantly
      increased out understanding of GCA.

PMID- 9643317
TI  - Vasculitis in systemic lupus erythematosus.
AB  - Vasculitis frequently complicates SLE, is associated with significant morbidity
      and mortality, and its pathophysiology is poorly understood. In seriously ill
      lupus patients with vasculitis, immunosuppression should almost always be
      considered.

PMID- 9643318
TI  - Mixed cryoglobulinaemia: a cross-road between autoimmune and lymphoproliferative
      disorders.
AB  - Mixed cryoglobulinaemia (MC) is a systemic vasculitis, secondary to the
      deposition in small and medium-sized blood vessels of circulating immune
      complexes, mainly the cryoglobulins, and complement. MC is characterised by a
      typical clinical triad (purpura, weakness, arthralgias) and by one or more organ
      involvement: chronic hepatitis, glomerulonephritis, peripheral neuropathy, skin
      ulcers and diffuse vasculitis. In a limited number of MC patients, a malignancy,
      that is B-cell non-Hodgkin's lymphoma or hepatocellular carcinoma, may also
      develop. Hepatitis C virus (HCV) infection has been found in the majority of
      patients with MC; the frequency of HCV markers (91%) was significantly higher
      than other rheumatic diseases (6.4%), namely systemic lupus, Sjogren's syndrome,
      rheumatoid arthritis and systemic sclerosis, or healthy controls (1.2%). The HCV
      infection of lymphoid tissues may represent the remote event leading to B
      lymphocyte proliferation responsible for autoantibodies and immune-complex
      production. In a similar way, HCV infection may also be involved in the
      pathogenesis of other autoimmune (glomerulonephritis, thyroiditis, lung fibrosis,
      autoimmune hepatitis, porphyria cutanea tarda) and lymphoproliferative disorders
      (monoclonal gammopathies, B-cell lymphomas). MC shares numerous clinico
      serological and pathological features with the above disorders. HCV seems to be
      their common etiological agent; however, a variable combination of unknown co
      factors (infectious, genetic, environmental) should be determinant for the
      appearance of different clinical patterns.

PMID- 9643319
TI  - Pathogenesis of vasculitis.
AB  - This review discusses current thoughts on the pathogenesis of vasculitis.
      Secondary vasculitides, frequently associated with infections or systemic
      autoimmune diseases, are, in most cases, characterized by immune deposits in the
      vessel wall, which probably underlies the development of lesions. In the primary
      vasculitides, immune deposits are generally absent. A group of primary
      vasculitides is, however, strongly associated with anti-neutrophil cytoplasmic
      autoantibodies (ANCA). Various in vitro and in vivo experimental data suggest
      that those ANCA are involved in the pathogenesis of lesions in the associated
      disorders.

PMID- 9643320
TI  - Wegener's granulomatosis: disease course, assessment of activity and extent and
      treatment.
AB  - Wegener's granulomatosis (WG) belongs to the group of necrotizing primary
      systemic vasculitides of unknown etiology, that are associated with anti
      neutrophil cytoplasmic antibodies. The pathological hallmark of WG is the
      coexistence of vasculitis and granuloma. Due to more sensitive diagnostic
      instruments, especially ANCA testing, the incidence of diagnosis of WG has risen
      in the past ten years. Although the precise pathophysiology is not understood
      yet, there is ample evidence that ANCA, which can lead to cytotoxic reactions in
      the vascular texture, play a major role, possibly promoted by a dysbalance in the
      anti-idiotypic network. The clinical disease course is typically two-phasic,
      beginning with a granulomatous inflammation of the upper respiratory tract, that
      usually is followed by a generalized vasculitic phase, that can range from mild
      organ dysfuntion to life threatening multi-organ failure. Consequently,
      diagnostic procedures, patients' assessment and therapeutic regimens need to be
      individualized, adapted to stage and activity of the disease as well as
      standardized.

PMID- 9643321
TI  - Neuropeptides: role in inflammatory skin diseases.
AB  - The cutaneous nervous system recently has been demonstrated to interact with
      multiple target cells in the skin and to mediate actions important in
      inflammatory conditions. Neuropeptides released by cutaneous neurons such as
      substance P (SP), vasointenstinal peptide (VIP), calcitonine gene regulated
      peptide (CGRP), proopiomelancortin (POMC) peptides and others modulate the
      function of immunocompetent and inflammatory cells as well as epithelial and
      endothelial cells. They have been found to function as mediators of cell
      proliferation, cytokine and growth factor production as well as adhesion molecule
      and cell surface receptor expression. In addition many cells including
      keratinocytes, fibroblasts, endothelial cells and inflammatory cells have been
      shown to release several neuropeptides and they express their corresponding
      receptors. These findings indicate that neuropeptides participate in the complex
      network of mediators that regulate cutaneous inflammation, hyperproliferation and
      wound healing.

PMID- 9643322
TI  - Leishmaniasis and the JEADV.

PMID- 9643323
TI  - American cutaneous leishmaniasis due to Leishmania (Viannia) guyanensis as an
      initial clinical presentation of human immunodeficiency virus infection.
AB  - The authors present the first report of Leishmania (Viannia) guyanensis (L.(V.)
      guyanenesis) associated with human immunodeficiency virus (HIV) in a Brazilian
      heterosexual man. It is also the first case of HIV infection associated with
      American cutaneous leishmaniasis in Brazilian Western Amazonia. The patient had
      cutaneous and mucous lesions with a negative Montenegro skin test. Histopathology
      showed large numbers of amastigotes, even in a lesion which had clinically
      healed. L.(V.) guyanenesis was typed by an immunoenzymatic technique. Various
      therapies were attempted, but the patient relapsed after each episode of
      treatment.

PMID- 9643324
TI  - American cutaneous leishmaniasis associated with HIV infection: report of four
      cases.
AB  - OBJECTIVE: A report of four cases of American cutaneous leishmaniasis associated
      with HIV infection is presented. BACKGROUND: The association of mucocutaneous
      leishmaniasis and HIV infection is rare. Only 15 cases have been reported in the
      literature thus far. SUBJECTS: Four new cases are described and the differences
      between the clinical presentation in immunocompromised and immunocompetent
      patients are emphasized. CONCLUSIONS: Multiple cutaneous lesions plus mucosal
      involvement characterize the clinical presentation of American cutaneous
      leishmaniasis in association with HIV infection in the majority of the cases. A
      serological investigation for HIV infection is recommended for patients
      presenting with this type of clinical picture, especially if the patient is a
      young male.

PMID- 9643325
TI  - Leishmaniasis of glans penis.
AB  - BACKGROUND: Leishmaniasis is an important protozoan disease. In the Americas it
      is produced by several species of the genus Leishmania, transmitted by sand flies
      of the genus Lutzomyia. Disease spectrum ranges from cutaneous ulceration to more
      serious involvement of oronasal mucosa that may progress to destruction of
      central structures of the face and to the life-threatening visceral forms.
      Leishmania Viannia braziliensis is the most widespread species in Brazil and is
      often associated with mucosal involvement. Cutaneous lesions are commonly
      localised in uncovered areas of the body. Genital lesions are rare. MATERIALS AND
      METHODS: A patient with an ulcerated lesion of the glans penis, followed
      subsequently by mucosal lesions of the nasal cavity and palate, is presented.
      Diagnostic procedures were: leishmanin skin test (Montenegro's test) and biopsy
      of the ulcer border processed for histopathological examination and culture in
      NNN medium. RESULTS: Leishmanin skin test was positive. Histopathology showed a
      granulomatous infiltrate containing some parasites. Culture was positive for
      Leishmania sp., and was later identified by zymodeme analysis and monoclonal
      antibodies as L.(V.) braziliensis. The patient was treated with pentavalent
      antimony at the dose of 10 (mg/kg)/day for 30 days and the lesions healed.
      COMMENTS AND CONCLUSIONS: In men, especially over 50 years of age, ulceration of
      the glans penis is highly suggestive of carcinoma. Precise differential diagnosis
      is imperative. A lesion, such as the one reported, may cause diagnostic
      difficulties when it presents in countries different from the source, where the
      condition is very uncommon. This is increasingly frequent in the current era of
      widespread air travel.

PMID- 9643326
TI  - Generalized cutaneous leishmaniasis in acquired immunodeficiency syndrome.
AB  - BACKGROUND: Leishmaniasis associated with HIV/AIDS has been reported in the last
      decade. CASE REPORT: A case of generalized cutaneous leishmaniasis in a patient
      with AIDS is described. The case is paradoxical in that the cutaneous lesions
      resemble anergic leishmaniasis caused by Leishmania (L.) amazonensis and Jorge
      Lobo's disease, but the positive Montenegro test and the clinical improvement
      with antimonial are more commonly observed in leishmaniasis caused by L.(V.)
      braziliensis. COMMENT: The immunosuppression due to HIV/AIDS seen in this patient
      may explain the dissemination of the lesions, but the positive specific response
      to leishmanial antigen may explain the good response to the antimonial treatment.

PMID- 9643327
TI  - Prevalence of bands other than 160 and 130 kDa in pemphigus sera (a multicenter
      immunoblotting study). Gruppo Italiano Studi Epidemiologici in Dermatologia
      (GISED).
AB  - Patients with pemphigus may produce antibodies against molecules other than the
      classical transmembranal ones. Recently, for example antibodies to 230 kDa
      antigens have been found in association with antibodies to intercellular
      substance. To better understand their prevalence, clinical correlates and
      prognostic significance of bands other than 130 and 160 kDa, we studied 67
      pemphigus sera. About one-fourth of patients revealed multiple heterogeneous
      bands and 13% the 230 kDa band. When challenged with the recombinant protein
      rBP55, the carbossiterminal portion of bullous pemphigoid major antigen, all 230
      kDa-positive-sera proved negative. Caution is to be recommended in interpreting
      pemphigus sera with a band migrating at the 230 kDa level.

PMID- 9643328
TI  - Anaerobic bacteria in men with urethritis.
AB  - AIM: Investigation of the urethral flora in men with urethritis, with particular
      reference to anaerobic bacteria. METHODS: Multiple cultures were performed on
      three urethral samples from 110 men attending the STD Clinic of the School of
      Medicine in Seville: 35 with no evidence of urethritis (control group), and 75
      with urethritis (17 gonococcal urethritis (GU) and 58 non-gonococcal urethritis
      (NGU)). In the 58 men with NGU, Chlamydia trachomatis was isolated in 16 (27.5%),
      Ureaplasma urealyticum in 18 (31%), Trichomonas vaginalis in two (3.4%) and no
      pathogens were isolated in the remaining 22 (38%) patients. RESULTS: Aerobic
      flora, mainly Staphylococcus spp., were isolated less frequently (41%) in
      patients with GU than in the control group (80%), and those with NGU (72%).
      Anaerobic flora were isolated in 62% of patients, with similar isolation rates in
      each group. Gram-negative anaerobes were more frequently isolated in men with
      urethritis, especially NGU, compared to controls (P < 0.05). Prevotella spp. and
      Bacteroides spp. were significantly more frequently isolated in patients with
      NGU, including Chlamydia-negative NGU. Fusobacterium spp. were more frequent in
      the Chlamydia-positive NGU than in the controls (P < 0.05). P. magnus was the
      most frequent anaerobic species found in the control group, while P. prevotii was
      most frequently seen in the urethritis group. B. ureolyticus, P. prevotii and P.
      tetradius were more frequent on the NGU group (P < 0.05). B. ureolyticus was
      commoner in patients with Chlamydia-negative NGU, while P. tetradius and P.
      asaccharolytica was commoner in those where C. trachomatis was isolated than in
      the control group. CONCLUSION: Urethral microflora isolated showed ten bacterial
      genus and 25 different species of anaerobes. The spectrum of these microflora
      changed with the presence of urethritis and varied with its aetiology.

PMID- 9643329
TI  - 'Suction split' as a routine method to differentiate epidermolysis bullosa
      acquisita from bullous pemphigoid.
AB  - BACKGROUND AND DESIGN: Epidermolysis bullosa acquisita (EBA) and bullous
      pemphigoid (BP) are diseases with similar clinical, histological, and
      immunofluorescent findings. Diagnosis requires the use of immunoelectron
      microscopy, immunoprecipitation or immunoblotting, but in recent years the
      differential diagnosis has been based on a cheaper technique named salt split
      skin. This study demonstrates that with a suction blister the fracture is at the
      same level as that obtained with the sodium split method and that it is also
      faster and cheaper. Suction blisters on normal skin and autoimmune perilesional
      bullous lesions, obtained with a hand vacuum pump, were studied by direct
      immunofluorescence and electron microscopy to evaluate the level of the split on
      normal suction split skin. Normal human split skin was also used as a substrate
      for an indirect immunofluorescent study using sera of patients with BP (68 sera),
      EBA (10 sera) and cicatricial pemphigoid (CP) (16 sera). Direct immunofluorescent
      examination was also done on perilesional skin after artificial separation
      obtained with a hand-vacuum pump in patients with the same diseases listed above
      (32 BP, 11 CP, 6 EBA). RESULTS: On normal human skin split by suction or sodium
      chloride (NaCl; 1 mol/l) direct immunofluorescence and electron microscopy
      demonstrated that the split is at the lamina lucida level. Indirect
      immunofluorescent study of both normal human skin and perilesional skin split
      using suction as a substrate showed IgG deposits localized on the floor of the
      suction blister in all cases of EBA, whereas in over 88% of cases of BP and in
      over 62% of CP the IgG were localized on the roof. Similar results were obtained
      with direct immunofluorescence in perilesional skin. CONCLUSIONS: 'Suction split'
      represents a simple technique to differentiate EBA from BP. This method provides
      final response in a few hours compared to at least 1-2 days with the sodium split
      method. Furthermore, the suction split method is cheaper and the tissue can be re
      utilized for molecular biology and immunohistochemical studies.

PMID- 9643330
TI  - A case of coumarin necrosis with penile and pedal involvement.
AB  - A 57-year-old male patient with advanced adenocarcinoma of the lung, who was
      administered oral anticoagulant therapy because of pulmonary embolism, developed
      coumarin necrosis confined to the penis and feet. To our knowledge, this patient
      showing acral involvement is the seventh case of coumarin-induced penile necrosis
      reported to date.

PMID- 9643331
TI  - Mycosis fungoides with involvement of the oral cavity.
AB  - Mycosis fungoides rarely involves the oral cavity. To our knowledge only 29 cases
      of oral cutaneous T-cell lymphoma have been described up to 1994. This report
      presents a case of mycosis fungoides with involvement of the oral cavity in a 57
      year-old man who died from septicemia 7 months after the onset of oral
      involvement.

PMID- 9643332
TI  - Idiopathic plantar hidradenitis.
AB  - We describe four cases of idiopathic plantar hidradenitis (IPH), a form of
      neutrophilic eccrine hidradenitis (NEH) localized on the feet of otherwise
      healthy young persons. Our patients were all males, 8-17 years old, in apparently
      good health, but presenting erythematous painful papules, plaques and nodules on
      the soles. They were afebrile and there were no constitutional symptoms. The
      differential diagnoses included erythema nodosum, vasculitis and traumatic
      plantar urticaria. The histological features of IPH are similar to those of NEH,
      except for the absence of syringosquamous metaplasia. The patients were treated
      with topical steroids and oral NSAID, with total resolution of the lesions in 1
      or 2 weeks.

PMID- 9643333
TI  - Palmar spiny keratoderma associated with type IV hyperlipoproteinemia.
AB  - We report the case of a 35-year-old man with acquired palmar spiny keratoderma
      (SK) in association with type IV hyperlipoproteinemia. Cutaneous lesions appeared
      11 years before with no history of any previous skin conditions, topical
      medication or systemic treatment with Vitamin A-derived drugs, x-irradiation,
      arsenic poisoning or prolonged sun exposure. Family aggregation for SK or other
      disorders of keratinization was ruled out. Blood chemistries demonstrated
      hypertriglyceridemia (422 mg/dl) and elevation in plasma concentration of the pre
      beta fraction (VLDL) of lipoproteins pattern compatible with a type IV
      hyperlipoproteinemia. Family aggregation for this metabolic defect was then
      confirmed. The histologic hallmark of the 'spine' lesion was a compact column of
      hyperparakeratotic cells (columnar hyperparakeratosis) continuous with a
      hypogranular layer, without further evidence of dyskeratotic or vacuolated
      keratinocytes and inflammatory cells in the corresponding dermis. SK represents a
      well-definite entity which fulfills precise clinico-histologic criteria. However,
      three main questions are related to SK: differential diagnosis with porokeratosis
      on histologic examination (columnar hyperparakeratosis or hyperorthokeratosis
      alone in SK vs. cornoid lamella accompanied by remarkable dermoepidermal changes
      in porokeratosis); classificative scheme (proper nomenclature to avoid misleading
      and confounding names); and nosological arrangement (probably two subsets exist:
      hereditary or benign; and acquired, or idiopathic, which may be paraneoplastic in
      about 50% of the patients). To the best of our knowledge this is the first case
      reporting the association between SK and a metabolic impairment although the real
      connections linking these conditions are still unclear.

PMID- 9643334
TI  - Fatal cytophagic histiocytic panniculitis after a short response to cyclosporine.
AB  - Cytophagic histiocytic panniculitis (CHP) is a disorder characterized by a
      histiocytic infiltrate in the subcutaneous adipose tissue which often extends to
      involve systemic organs. Fever, pancytopenia, hepatosplenomegaly, mucosal ulcers
      and serositis are common systemic symptoms. Although remissions have been
      reported, the disease tends to follow a chronic course often complicated by
      terminal hemorrhagic diathesis and death. Several reports in the recent
      literature have suggested that cyclosporine is the treatment of choice in CHP. We
      report the first case of cyclosporine treatment failure in CPH. Despite an
      initial response to treatment and persistent resolution of cutaneous lesions, the
      internal disease progressed resulting in the patient's death. Therefore the
      evolution of skin lesions and signs of systemic involvement may not be an
      accurate assessment of disease activity in patients with CHP being treated with
      cyclosporine.

PMID- 9643335
TI  - Verrucoid cutaneous rhinosporidiosis.
AB  - Verruca vulgaris like lesions of cutaneous rhinosporidiosis are reported in a
      middle aged Indian male. He also had nasal rhinosporidiosis. Imprint smears from
      skin lesions showed sporangia with endospores, confirming the diagnosis.

PMID- 9643336
TI  - Cutaneous larva migrans associated with water shoe use.
AB  - It has been long suspected that footwear is protective against cutaneous larva
      migrans. This case report describes a woman who developed cutaneous larva migrans
      despite wearing 'protective' footwear. We forward a hypothesis by which recently
      popular water shoes may actually be conducive to the development of cutaneous
      larva migrans rather than having a protective function.

PMID- 9643337
TI  - Cytarabine-induced acral erythema: a localized form of toxic epidermal
      necrolysis?

PMID- 9643338
TI  - Human papilloma virus infection in the oral cavity--a source of infection.

PMID- 9643339
TI  - Calciphylaxis in chronic renal failure.

PMID- 9643340
TI  - A probable role of an infectious agent in polymyositis associated with antibodies
      against histidyl-tRNA synthetase: antisynthetase syndrome.

PMID- 9643341
TI  - Lymphomatoid papulosis and progression to T-cell immunoblastic lymphoma.

PMID- 9643342
TI  - Acne due to amineptine abuse.

PMID- 9643343
TI  - PUVA therapy in localized scleroderma.

PMID- 9643344
TI  - Reduction of phosphatidylcholine hydroperoxide by apolipoprotein A-I:
      purification of the hydroperoxide-reducing proteins from human blood plasma.
AB  - Plasma glutathione peroxidase (GSHPx) has been suggested to reduce submicromolar
      levels of free fatty acid hydroperoxides and phosphatidylcholine hydroperoxides
      (PC-OOH), and therefore these hydroperoxides are undetectable in human blood
      plasma. The capacity for the reduction should be about 2.5 microM as the level of
      glutathione in human plasma is about 5 microM. However, 2 h of aerobic incubation
      of 58 microM PC-OOH in human plasma at 37 degrees C resulted in the formation of
      36 microM phosphatidylcholine hydroxide (PC-OH). The presence of PC-OOH-reducing
      protein other than plasma GSHPx was suggested by the results. a) The same rates
      of PC-OOH decay and PC-OH formation were observed in both sera from rats with
      selenium-deficient and selenium-supplemented diet; b) the PC-OOH-reducing
      activity was observed only in the high molecular weight fraction but not in the
      low molecular weight fraction; and c) albumin did not work as a reducing
      substrate of plasma GSHPx. We have isolated two hydroperoxide-reducing protein
      fractions from human plasma by a sequential purification scheme, comprising an
      ammonium sulfate precipitation followed by sequential chromatography on anion
      exchange, hydrophobic interaction, and heparin columns. One of the proteins was
      identified as apolipoprotein A-I by N-terminal amino acid sequence analysis.
      Moreover, the hydroperoxide-reducing activity of one of the fractions was
      inhibited almost completely by the addition of anti-apolipoprotein A-I antibody.
      These findings demonstrate that apolipoprotein A-I in high density lipoprotein
      can reduce PC-OOH to PC-OH.

PMID- 9643345
TI  - Effects of heterozygous lipoprotein lipase deficiency on diet-induced
      atherosclerosis in mice.
AB  - Heterozygous lipoprotein lipase deficiency (LPL+/-) is common and has been
      implicated in premature atherosclerosis in epidemiologic studies. However, in
      vitro data suggest that LPL deficiency in the vascular wall may be
      antiatherogenic. To address the role of LPL in atherosclerosis, LPL+/- mice in
      the C57BL/6J background were fed an atherogenic diet for 8 months. LPL+/- mice
      were more dyslipidemic than +/+ animals due to increased concentrations of non
      HDL lipoproteins. There was no difference in aortic origin atherosclerosis
      between LPL+/- (n=56) and +/+ (n=55) mice. LPL+/- mice in the low density
      lipoprotein receptor knockout (LDLR-/-) background were fed the same atherogenic
      diet for 3 months. LPL+/-LDLR-/- mice were more dyslipidemic than LPL+/+LDLR-/-
      animals. There was no difference in atherosclerosis assayed for the entire aorta
      and no difference in aortic sterol content between LPL+/-LDLR-/- (n=28) and
      LPL+/+LDLR-/- (n=15) mice. LPL protein was detected in murine lesions in a
      consistent layered pattern. More luminal, lipid-laden macrophages generally did
      not stain for LPL, but deeper, lipid-poor macrophages as well as necrotic core
      regions contained immunoreactive LPL. LPL protein was more abundant in lesions
      from LPL+/+ LDLR-/- than LPL+/-LDLR-/- mice. After eating an atherogenic diet,
      LPL+/- as compared to LPL+/+ mice have more dyslipidemia, but no more
      atherosclerosis, and less LPL protein in atherosclerotic lesions. These data
      suggest that lipoprotein lipase deficiency in the vascular wall could prevent the
      retention of atherogenic lipoproteins.

PMID- 9643346
TI  - Synthesis and accumulation of a receptor regulatory protein associated with lipid
      droplet accumulation in 3T3-L1 cells.
AB  - Synthesis and accumulation of the recently identified prostaglandin F2alpha
      receptor regulatory protein (FPRP) was found to correlate closely with lipid
      droplet accumulation by 3T3-L1 preadipose cells. FPRP, a transmembrane
      glycoprotein, has been shown to regulate the binding of ligand to certain seven
      transmembrane receptors. Anti-FPRP immunohistochemistry, Western blotting, and
      metabolic labeling/immunoprecipitation experiments demonstrated that FPRP was not
      detectable in undifferentiated 3T3-L1 cells. Interestingly, low levels of FPRP
      mRNA were detected in the undifferentiated 3T3-L1 cells. After induction of
      adipose differentiation, FPRP mRNA increased approximately 3 fold whereas FPRP
      synthesis increased approximately 50 fold. Differentiation induction with either
      dexamethasone/insulin/isobutylmethylxanthine or the thiazolidinedione derivative
      ADD 4743 were both effective at inducing FPRP accumulation and accumulation of
      lipid droplets. By co-immunohistochemical and lipid staining, greater than 99% of
      the cells accumulating lipid droplets possessed FPRP. FPRP mRNA and protein are
      also found in rat adipose tissue. Treatment of 3T3-L1 cells with an FPRP anti
      sense oligonucleotide during differentiation decreased FPRP accumulation and
      resulted in a decrease in lipid droplets without altering the level of induction
      of a late marker of adipocyte differentiation, glycerol-3-phosphate dehydrogenase
      activity. Transient expression of an FPRP cDNA in undifferentiated 3T3-L1 cells
      was insufficient to induce lipid droplet accumulation.

PMID- 9643347
TI  - Analysis of particle size and lipid composition as determinants of the metabolic
      clearance of human high density lipoproteins in a rabbit model.
AB  - Hypertriglyceridemia is commonly associated with triglyceride (TG) enrichment of
      high density lipoprotein (HDL) and reduction in HDL cholesterol and
      apolipoprotein A-I levels. We have recently reported that lipolytic modification
      of TG-rich HDL, which reduces particle size, enhances its clearance from the
      circulation. In the present study, we examined the role of particle size and
      lipid composition in determining the metabolic clearance of human HDL, in the
      absence of substantial in vivo modification of the particle by hepatic lipase.
      The rabbit, which has a very low hepatic lipase activity, was used for this
      purpose. Plasma fractions d < 1.21 g/ml were first isolated by
      ultracentrifugation from fasting humans with normal (NTG, n=6, mean plasma TG
      concentration=1.26+/-0.21 (SEM) mmol/l) or elevated plasma TG levels (HTG, n=5,
      TG=4.49+/-0.65 mmol/l). Small and large HDL particles were separated by gel
      filtration chromatography and were labeled with either 125I or (131)I. Large HDL
      were cleared more rapidly than small HDL in 10 out of 11 studies (P=0.006). There
      was, however, no difference in the fractional catabolic rate (FCR) of large HDL
      isolated from NTG versus from HTG subjects or in the FCR of small HDL from NTG
      versus HTG individuals. There was also no correlation between the TG content of
      HDL and its FCR. In summary, large, lipid-rich human high density lipoproteins
      (HDL) are cleared more rapidly than small human HDL in rabbits. These results,
      combined with our previous observation, also support the hypothesis that
      triglyceride enrichment of HDL, in the absence of substantial lipolytic
      modification, is not sufficient to enhance its clearance from the circulation.

PMID- 9643348
TI  - The carboxyl terminus in apolipoprotein E2 and the seven amino acid repeat in
      apolipoprotein E-Leiden: role in receptor-binding activity.
AB  - Both apolipoprotein (apo) E2 and apoE-Leiden (tandem repeat of amino acids 121
      127) are associated with type III hyperlipoproteinemia and bind defectively to
      low density lipoprotein receptors. Removing the carboxyl terminus of both
      variants (residues 192-299) increases receptor-binding activity, suggesting that
      the carboxyl terminus modulates activity. To identify the region(s) that
      modulated binding activity, we produced carboxyl-terminal truncations in apoE2
      and apoE-Leiden (terminating at positions 191, 223, 244, and 272) and in apoE3
      (terminating at positions 191, 223, and 244) and compared their receptor-binding
      activities as dimyristoylphosphatidylcholine (DMPC) discs. The results suggest
      that the entire carboxyl terminus up to residue 272, not a discrete smaller
      segment, is responsible for the modulation in apoE2. Intact apoE-Leiden and the
      223 and 244 variants displayed similar activities (approximately 25% of apoE3's),
      but the 191 variant's activity was identical to that of intact apoE3. ApoE-Leiden
      and its truncated variants formed larger DMPC discs than did intact or truncated
      apoE3 or apoE2. These discs contained more apoE molecules than apoE3 discs,
      suggesting that the apparently normal binding activity of the apoE-Leiden 191
      variant results from an increased number of apoE molecules and that the binding
      activity is actually defective. Direct comparison in a solid-phase assay revealed
      that the binding activity of the apoE-Leiden fragment was defective (51.4+/
      9.4%). Thus, the defective binding of apoE-Leiden results from a direct effect of
      the seven amino acid repeat on receptor-binding activity rather than from an
      indirect effect operating through the carboxyl terminus as previously believed.

PMID- 9643349
TI  - Effects of dietary fish oil on serum lipids and VLDL kinetics in hyperlipidemic
      apolipoprotein E*3-Leiden transgenic mice.
AB  - Studying the effects of dietary fish oil on VLDL metabolism in humans is subject
      to both large intra- and interindividual variability. In the present study we
      therefore used hyperlipidemic apolipoprotein (APO) E*3-Leiden mice, which have
      impaired chylomicron and very low density lipoprotein (VLDL) remnant metabolism,
      to study the effects of dietary fish oil on serum lipids and VLDL kinetics under
      highly standardized conditions. For this, female APOE*3-Leiden mice were fed a
      fat- and cholesterol-containing diet supplemented with either 0, 3 or 6% w/w
      (i.e. 0, 6, or 12% of total energy) of fish oil. Fish oil-fed mice showed a
      significant dose-dependent decrease in serum cholesterol (up to -43%) and
      triglyceride levels (up to -60%), mainly due to a reduction of VLDL (-80%). LDL
      and HDL cholesterol levels were not affected by fish oil feeding. VLDL-apoB
      kinetic studies showed that fish oil feeding resulted in a significant 2-fold
      increase in VLDL-apoB fractional catabolic rate (FCR). Hepatic VLDL-apoB
      production was, however, not affected by fish oil feeding. VLDL-triglyceride
      turnover studies revealed that fish oil significantly decreased hepatic VLDL
      triglyceride production rate (-60%). A significant increase in VLDL-triglyceride
      FCR was observed (+70%), which was not related to increased lipolytic activity.
      We conclude that APOE*3-Leiden mice are highly responsive to dietary fish oil.
      The observed strong reduction in serum very low density lipoprotein (VLDL) is
      primarily due to an effect of fish oil to decrease hepatic VLDL triglyceride
      production rate and to increase VLDL-apoB fractional catabolic rate.

PMID- 9643350
TI  - LPL promoter -93T/G transition influences fasting and postprandial plasma
      triglycerides response in African-Americans and Hispanics.
AB  - The lipoprotein lipase (LPL) promoter -93T/G transition has previously been
      reported as having a triglyceride (Tg)-lowering effect, whereas the D9N variant
      has been shown to have a Tg-raising effect. These two variants were studied in 66
      healthy subjects of Hispanic and 42 subjects of African-American origin, who had
      participated in a study of postprandial lipemia. While the allele frequency of
      the -93G was significantly different in the Hispanics and African Americans
      (0.09: 95% CI 0.04-0.13 and 0.28: 95% CI 0.19-0.38; P=0.0001, respectively), the
      N9 allele frequency was not different (0.06: 95% CI 0.02-0.1 and 0.05: 95% CI
      0.002-0.093, respectively). Linkage disequilibrium between the -93T/G and D9N was
      highly significant in Hispanics (delta=0.67. P=0.0001), compared to delta=0.09
      (NS) in African-Americans. In the combined group, compared to individuals with
      the common genotype (TT/DD; n=71) with fasting plasma Tg of 1.34 (+/-4.5% SEM)
      mmol/l, carriers of the G/D haplotype (TG/DD + GG/DD; n=25) had significantly
      lower plasma Tg levels of 1.08 (+/-10% SEM) mmol/l (P < 0.02). After the fat
      meal, compared to individuals with neither mutation, TT/DD, the effect of the G/D
      haplotype was to reduce significantly postprandial Tg (P < 0.036). Retinyl
      palmitate concentration at 5 hrs was significantly lower in G/D carriers than
      TT/DD individuals (P < 0.05). The lipid-raising effect of the N9 allele in
      carriers of the -93G (TG/DN + GG/DN) and effect on postprandial Tg clearance was
      not significant in this group. Thus carriers of the G/D haplotype have lower
      fasting plasma Tg and reduced alimentary lipemia. This allele may be associated
      with reduced risk of coronary artery disease.

PMID- 9643351
TI  - Phospholipase A2 relieves phosphatidylcholine inhibition of micellar cholesterol
      absorption and transport by human intestinal cell line Caco-2.
AB  - Cholesterol absorption from bile acid micelles is suppressed by
      phosphatidylcholine (PC) in the micelles. The effects of micellar phospholipid
      composition on absorption, metabolism, and secretion of lipids were examined in
      Caco-2 cells incubated with micelles composed of taurocholic acid, cholesterol,
      oleic acid, monooleoylglycerol, and phospholipid. Significant amounts of all
      micelle lipids were absorbed from micelles lacking phospholipid. Cholesterol
      absorption was accompanied by cholesterol esterification and secretion. Micellar
      oleic acid was also absorbed and reesterified primarily into triacylglycerol
      which was also secreted. Lipid absorption and secretion from micelles containing
      lysophosphatidylcholine (LPC) were similar to that obtained with phospholipid
      free micelles. LPC was also extensively absorbed. In contrast, incubations with
      PC-containing micelles resulted in large reductions in the absorption,
      esterification, and secretion of cholesterol without significant decreases in
      oleic acid absorption, conversion to acylated lipids, or triacylglycerol
      secretion. A relatively small reduction in monoacylglycerol absorption from PC
      containing micelles was detected. Retinol absorption was not affected by micellar
      PC. Substitution of LPC for half or more of the PC reversed the PC-dependent
      decrease in cholesterol absorption. Pancreatic phospholipase A2 (pPLA2) enhanced
      cholesterol absorption from PC-containing micelles. The pPLA2-dependent increase
      in cholesterol absorption was inhibited by the pPLA2 inhibitor FPL 67047XX. The
      results indicate micellized cholesterol absorption by enterocytes is uniquely
      dependent on the elimination of micellar phosphatidylcholine and thus directly
      dependent on the lipolytic action of pancreatic phospholipase A2 (pPLA2).
      Consequently, pPLA2 inhibitors may be a new and novel class of cholesterol
      absorption inhibitors for therapeutic use.

PMID- 9643352
TI  - Involvement of cytochrome P450 2E1 in the (omega-1)-hydroxylation of oleic acid
      in human and rat liver microsomes.
AB  - In vitro techniques have been used to investigate the nature of microsomal
      cytochrome P450 involved in the metabolism of oleic acid, a physiological
      monounsaturated fatty acid. Like lauric acid, which is currently used as a model
      substrate of fatty acid metabolism, the alkyl chain of oleic acid is hydroxylated
      on its omega and (omega-1) carbons. The identity of these hydroxylated
      metabolites was ascertained by GC/MS and LC/MS. The omega/omega-1 ratio of oleic
      acid metabolites (1.22+/-0.01) was found to be similar to that obtained with
      lauric acid in rat liver microsomes (1.10+/-0.02), while in human liver
      microsomes this ratio was 0.75+/-0.5 for lauric acid and 5.2+/-2.6 for oleic
      acid. After treatment of rats with ethanol or clofibrate, inducers of CYP2E1 and
      CYP4A, respectively, the hydroxylations of oleic acid were shown to be less
      inducible than those of lauric acid. Five in vitro approaches were used to
      identify the P450 isoform(s) responsible for the microsomal (omega-1)
      hydroxylation of oleic acid: effect of various inducers in rats, correlation
      studies between specific P450 catalytic activities in a panel of 25 human liver
      microsomes, chemical inhibitions, immuno-inhibitions and metabolism by cDNA
      expressed human P450 enzymes. From the above results, it can be ascertained that
      P450 2E1 is the main enzyme involved in the (omega-1)-hydroxylation of oleic
      acid. Furthermore, the omega-hydroxylation of oleic acid was shown to be mainly
      catalyzed by P450 4A enzymes in human liver microsomes. The turnover number of
      (omega-1)-hydroxylation of lauric and oleic acids decreased from 7.8 to 1.5 min(
      1), respectively, suggesting that the dodecane alkyl chain allows optimal binding
      to the active site of CYP2E1.

PMID- 9643353
TI  - Regulation of microsomal triglyceride transfer protein mRNA expression by
      endotoxin and cytokines.
AB  - We studied the effect of endotoxin (LPS), and cytokines (TNF, IL-1, and IL-6) on
      hepatic microsomal triglyceride transfer protein (MTP) mRNA levels in vivo in
      Syrian hamsters and in vitro in HepG2 cells. LPS, interleukin-1 (IL-1), and to a
      lesser extent tumor necrosis factor (TNF) significantly decreased MTP mRNA levels
      in hamster liver. These effects required several hours. Furthermore, IL-1 and IL
      6 significantly decreased MTP mRNA levels in HepG2 cells. This decrease appeared
      soon after IL-1 administration (8 h) and at very low doses (0.1 ng/ml). MTP
      activity and protein levels of the large subunit of MTP also decreased modestly
      in HepG2 cells with prolonged cytokine treatment. IL-1 reduced the expression of
      an MTP promoter luciferase construct to a similar degree as seen with MTP mRNA,
      indicating that transcriptional regulation plays a major role in the decrease of
      MTP gene expression. Deletional analysis of the MTP promoter identified the
      region -121 to -88 bp upstream to the coding sequence as the site of the negative
      regulation by IL-1. This region contains an insulin response element (IRE),
      activating protein 1 (AP-1), hepatic nuclear factor 1 (HNF-1) and hepatic nuclear
      factor 4 (HNF-4) consensus sequences; mutations of the IRE and HNF-4 sites did
      not affect the response to IL-1. In contrast, mutating AP-1 or HNF-1 sites led to
      a marked decrease in basal expression and the loss of the IL-1 effect, suggesting
      that an intact AP-1 and/or HNF-1 regulatory element are crucial for the IL-1
      regulation of MTP gene expression. However, prolonged incubation with IL-1 did
      not alter HepG2 apolipoprotein B secretion suggesting that MTP mRNA down
      regulation does not contribute significantly to the cytokine-induced effects on
      lipid metabolism.

PMID- 9643354
TI  - Differential rate of cholesterol efflux from the apical and basolateral membranes
      of MDCK cells.
AB  - Epithelial cells contain two distinct membrane surfaces, the apical and
      basolateral plasma membranes, which have different lipid and protein
      compositions. In order to assess the effect of the compositional differences of
      the apical and basolateral membranes on their ability to undergo cholesterol
      efflux, MDCK cells were radiolabeled with [3H]cholesterol and grown as a
      polarized monolayer on filter inserts, that separate the upper apical compartment
      from the lower basolateral compartment. The rate of cholesterol efflux from the
      basolateral membrane into media containing HDL in the basolateral compartment was
      6.3%/h +/-0.7, whereas HDL-mediated efflux from the apical membrane was
      approximately 3-fold slower (1.9%/h +/-0.3). In contrast, Fu5AH cells, which do
      not form distinct polarized membrane domains, had a similar rate of HDL-mediated
      cholesterol efflux into the apical and basolateral compartments. Similar to HDL,
      other cholesterol acceptors, namely LDL, bovine serum albumin, and a lipid
      emulsion, also showed a decreased rate of cholesterol efflux from the apical
      membrane surface versus the basolateral membrane. Compared to the basolateral
      membrane, the apical membrane was also found to be more resistant to cholesterol
      oxidase treatment, to bind less HDL, and to take up less cholesterol from the
      medium. In conclusion, cholesterol efflux occurred less readily from the apical
      membrane than from the basolateral membrane for all types of acceptors tested.
      These results suggest that differences in the composition of the apical and
      basolateral membrane lead to a relative decrease in cholesterol desorption from
      the apical membrane and hence a reduced rate of cholesterol efflux.

PMID- 9643355
TI  - Liposomes enriched in oleic acid are less susceptible to oxidation and have less
      proinflammatory activity when exposed to oxidizing conditions.
AB  - As there is frequently a reciprocal relationship between oleic acid and linoleic
      acid content in LDL after dietary supplementation, it is difficult to determine
      the independent effects of oleic and linoleic acid on LDL oxidation. It is also
      unknown whether monounsaturated fatty acid enrichment might reduce the generation
      of proinflammatory products that occur when the polyunsaturated fatty acid-rich
      phospholipids within lipoproteins undergo mild oxidation. To address these
      issues, we exposed liposomes containing variable amounts of oleic, linoleic, and
      arachidonic acid to oxidizing conditions. Liposomes enriched in oleic acid but
      with constant amounts of linoleic acid were less susceptible to oxidation and had
      significantly greater lag times and time to half maximum conjugated diene
      formation. When mildly oxidized, liposomes containing either linoleic acid or
      arachadonic acid increased monocyte chemotaxis and monocyte adhesion to
      endothelial cells nearly 5-fold, demonstrating that oxidation products of both
      these polyunsaturated fatty acids are bioactive. The addition of a platelet
      activating factor receptor antagonist to endothelial cells inhibited stimulation
      of monocyte adhesion by oxidized liposomes, suggesting that some bioactive
      oxidation products of polyunsaturated fatty acids may resemble platelet
      activating factor in structure. In contrast, when liposomes were enriched in
      oleic acid, monocyte chemotaxis and monocyte adhesion were nearly completely
      inhibited. These results suggest that enriching lipoproteins with oleic acid may
      reduce oxidation both by a direct "antioxidant"-like effect and by reducing the
      amount of linoleic acid available for oxidation as well as reduce the generation
      of bioactive particles that occur during mild oxidation.

PMID- 9643356
TI  - Adenovirus mediated overexpression of human phospholipid transfer protein alters
      plasma HDL levels in mice.
AB  - To study the function of plasma phospholipid transfer protein (PLTP) in vivo, a
      liver directed adenoviral gene transfer system was used to overexpress human PLTP
      in mice. For the experiments, two strains of mice, wild type (C57/B1) and mice
      transgenic for the human apoA-I gene (HuApoA-ITg), were utilized. Five days after
      injection of the recombinant PLTP adenovirus, wild type mice showed a 4-fold
      increase in serum PLTP activity in (12.2+/-1.3 micromol/ml per h to 48.1+/-8.6
      micromol/ml per h (+394%), P < 0.001). The PLTP overexpression induced
      significant reduction of serum cholesterol (2.46+/-0.08 to 0.69+/-0.42 mmol/l (
      72%), P < 0.001), phospholipids (3.10+/-0.06 to 0.90+/-0.24 mmol/l (-71%), P <
      0.01), and triglycerides (0.2+/-0.07 to 0.08+/-0.03 mmol/l (-69%), (P < 0.001).
      ApoA-I was hardly detectable in the serum. These lipid changes were due to a
      dramatic reduction of high density lipoprotein (HDL). The HuApoA-ITg mice
      displayed higher basal HDL level and PLTP activity. Adenovirus mediated PLTP
      overexpression in these mice resulted in a similar decrease of the lipid levels
      as that seen in the C57/B1 mice. However, the lipoprotein profile revealed a
      redistribution of HDL, with the appearance of larger buoyant HDL species. The
      results demonstrate that plasma phospholipid transfer protein in vivo causes high
      density lipoprotein (HDL) conversion and thereby plays a central role in HDL
      metabolism.

PMID- 9643357
TI  - 13-hydroxy octadecadienoic acid (13-HODE) inhibits triacylglycerol-rich
      lipoprotein secretion by CaCo-2 cells.
AB  - Oxidized lipids present in atherogenic lipoproteins are derived, in part, from
      the diet. To address the effects of an oxidized lipid on intestinal lipoprotein
      assembly and secretion, CaCo-2 cells were incubated with 13-HODE or its native
      fatty acid, linoleic acid, and triacylglycerol-rich lipoprotein synthesis and
      secretion were investigated. 13-HODE was readily taken up by cells and esterified
      to lipids. Although both fatty acids were largely esterified to neutral lipids,
      in comparison to neutral lipids containing linoleic acid, a greater proportion of
      cellular neutral lipids containing 13-HODE and/or its metabolites was secreted.
      Compared to linoleic acid, however, 13-HODE caused less triacylglycerol, derived
      from de novo synthesis, and less triacylglycerol mass to be secreted. Cells
      incubated with both linoleic acid and 13-HODE together secreted less
      triacylglycerol mass than did cells incubated with linoleic acid alone. Less
      newly synthesized apoB and apoB mass were secreted by cells incubated with 13
      HODE without altering the abundance of apoB mRNA. The fraction of newly
      synthesized apoB translocated into the secretory pathway of cells exposed to 13
      HODE was significantly less than that observed in cells incubated with linolenic
      acid, suggesting that 13-HODE interfered with the assembly and secretion of
      triacylglycerol-rich lipoprotein particles.

PMID- 9643358
TI  - Small dense low density lipoprotein has increased affinity for LDL receptor
      independent cell surface binding sites: a potential mechanism for increased
      atherogenicity.
AB  - Small dense low density lipoprotein (LDL) particles have altered apolipoprotein
      (apo) B conformation and lowered affinity for the LDL receptor (J. Biol. Chem.
      1994. 269: 511-519). Herein, we examine the interaction of small dense LDL with
      cell LDL receptor-independent binding sites. Compared to normal LDL, at low LDL
      cell media concentrations (<10 microg/ml), small dense LDL had decreased specific
      binding to the LDL receptor on normal fibroblasts at 4 degrees C, but a 2-fold
      increased binding to LDL receptor-independent cell sites. At higher LDL
      concentration (100 microg/ ml), LDL receptor-independent binding of small dense
      LDL was 4.5-fold that of normal LDL in normal fibroblasts, but greater (2- to 14-
      fold) in LDL receptor-negative fibroblasts. In LDL receptor-negative fibroblasts
      at 37 degrees C, small dense LDL had higher (3-fold) cell association than normal
      size LDL but no effective LDL degradation. At high LDL concentrations (> or =100
      microg/ml), LDL binding to normal or LDL receptor-negative fibroblasts was not
      affected by several anti-apoB monoclonal antibodies or by cell pretreatment with
      proteases, chondroitinase, or neuraminidase. In contrast, pretreating normal and
      receptor-negative fibroblasts with heparinase and heparitinase decreased LDL cell
      binding by 35% and 50%, respectively. Similarly, preincubation of receptor
      negative fibroblasts with sodium chlorate, an inhibitor of proteoglycan
      sulfation, decreased LDL binding by about 45%. We hypothesize that small dense
      LDL might be more atherogenic than normal size LDL due to decreased hepatic
      clearance by the LDL receptor, and enhanced anchoring to LDL receptor-independent
      binding sites in extrahepatic tissues (e.g., the arterial wall), a process
      mediated, in part, by cell surface proteoglycans.

PMID- 9643359
TI  - Effect of diet on the rate of depletion of n-3 fatty acids in the retina of the
      guinea pig.
AB  - This study has assessed the influence of maternal n-3 long chain polyunsaturated
      fatty acid supply and dietary manipulation after weaning on the retinal
      polyunsaturated fatty acid profile. Infant guinea pigs born of dams fed one of
      two commercial chow diets (differing in the amount of eicosapentaenoic,
      docosapentaenoic, and docosahexaenoic acids) were raised in two separate
      experiments, and subsequently partitioned into two diet groups, one supplied with
      a high level of alpha-linolenic acid (canola oil supplemented), the other with a
      very low level of alpha-linolenic acid (safflower oil supplemented). Guinea pigs
      born of dams supplied with the longer chain n-3 fatty acids in the commercial
      pellets (experiment 2) showed higher levels of retinal docosahexaenoic acid at
      weaning compared with those born to dams fed chow containing only alpha-linolenic
      acid (experiment 1). The rate of depletion of retinal docosahexaenoic acid after
      weaning onto the safflower oil diet was described by a two-stage exponential
      decay, possibly reflecting systemic and local conservation mechanisms, in
      conditions of dietary n-3 fatty acid deprivation. The rate of docosahexaenoic
      acid depletion in the group with the lower retinal docosahexaenoic acid at
      weaning was more than double the rate of depletion in the group with the higher
      weaning docosahexaenoic acid value. The endpoint retinal docosahexaenoic acid
      level at 16 weeks post-weaning after dietary n-3 fatty acid depletion on the
      safflower oil diet in the group, which started with the lower retinal
      docosahexaenoic acid level, was approximately half that compared with the group
      from the dams fed long chain n-3 fatty acids (experiment 1, 5% (interpolated),
      experiment 2, 9%). These results suggest that an adequately supplied mother is
      capable of providing an infant with enough n-3 fatty acids to withstand a longer
      period of dietary deprivation imposed after weaning.

PMID- 9643360
TI  - Hepatic secretion of VLDL fatty acids during stimulated lipogenesis in men.
AB  - Fatty acids (FA) that are utilized for triglyceride (TG) synthesis in the liver
      and principally from two sources: FA synthesized de novo in the liver and
      preformed FA. We have measured the contribution from the two sources to very low
      density lipoprotein (VLDL) TG synthesis individually for palmitate, oleate,
      stearate, and linoleate (approximately 98% of the total FA of VLDL TG (VLDL
      TGFA)) by isotopomer analysis. Five healthy men were studied in the basal state,
      and 1 (day 1) and 4 days (day 4) after the start of a hypercaloric carbohydrate
      enriched diet (approximately 2.5 times energy expenditure). The secretion of de
      novo palmitate was increased 15- and 43-fold after 1 and 4 days of
      hyperalimentation (2.6+/-1.2 (basal state), 40.8+/-20.0 (day 1), and 113.3+/-42.0
      micromol/kg per d (day 4)). Even though 4 days of hyperalimentation increased the
      secretion of de novo stearate 43-fold and de novo oleate 70-fold (stearate; 0.2+/
      0.2 (basal), 8.6+/-3.3 micromol/kg per d (day 4), oleate; 0.4+/-0.4 (basal),
      28.2+/-12.7 micromol/kg per d (day 4)), palmitate accounted for 75-85% of all the
      de novo VLDL TGFA. One day of carbohydrate hyperalimentation tended to decrease
      the secretion while 4 days increased the secretion of all preformed FA in VLDL
      TG. The rate of secretion of preformed palmitate and oleate were almost identical
      (palmitate; 80.2+/-22.2 (basal), 45.1+/-23.8 (day 1), and 256.2+/-74.1
      micromol/kg per d (day 4), oleate; 95.2+/-22.8 (basal), 46.2+/-24.2 (day 1), and
      356.8+/-74.1 micromol/kg per d (day 4)) and collectively these two FA accounted
      for 80-90% of the secretion from the preformed source. Palmitate is the
      predominant product of acute and prolonged carbohydrate mediated lipogenesis in
      the human liver. The pathway of further elongation and subsequent desaturation of
      de novo synthesized palmitate to generate stearate and oleate is inducible but,
      quantitatively, of minor significance in hepatic lipogenesis.

PMID- 9643361
TI  - Translocational pausing of apolipoprotein B can be regulated by membrane lipid
      composition.
AB  - One potential mechanism by which apolipoprotein (apo) B secretion is regulated is
      via transient pausing during translocation across the endoplasmic reticulum
      membrane. We have previously shown that translocation and secretion of full
      length and truncated variants of apoB 100 are impaired in hepatocytes in which
      microsomal membranes are enriched in the phospholipid
      phosphatidylmonomethylethanolamine (PMME). We have now investigated whether or
      not the decreased translocation of apoB is the result of altered membrane lipid
      composition having an impact on translocational pausing. Our experiments showed
      that less in vitro translated apoB-15 (the N-terminal 15% of human apoB-100) was
      translocated into the lumen of PMME-enriched microsomes than of control
      microsomes. Proteinase K treatment of the translocation products yielded discrete
      N-terminal fragments of apoB indicating that both types of microsomal membranes
      contained translocationally paused nascent chains. Similarly, apoB generated from
      a truncated mRNA lacking a stop codon was also found to be translocationally
      paused. However, restarting of translocation after translocational pausing was
      impaired in PMME-enriched, but not in control, microsomes. These data suggest
      that secretion of apoB-containing lipoproteins can be regulated by membrane lipid
      composition at the level of translocational pausing.

PMID- 9643362
TI  - Metabolic fate of platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero
      3-phosphocholine) and lyso-PAF (1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine) in
      FRTL5 cells.
AB  - The metabolism of platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero
      3-phosphocholine) and lyso-PAF (1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine) was
      investigated in FRTL5 cells, a normal rat thyroid cell line. FRTL5 cells
      incorporated [3H]PAF and deacetylated this compound to the corresponding [3H]lyso
      PAF which was not accumulated or secreted but converted mainly to alkyl-acyl
      phosphocholine indicating that this acylation process was particularly active in
      these cells. Among metabolic products of both [3H]PAF and [3H]lyso-PAF were
      alkylglycerol as well as its mono- and diacyl derivatives. [3H]alkylglycerol
      could be the intermediate compound for the production of [3H]alkyl- and
      [3H]alkenyl-phosphoethanolamine (plasmalogen) which were also metabolic products.
      FRTL5 cells were able to convert lyso-PAF to PAF especially when they were
      stimulated by ionophore A23187 in the presence of [3H]Iyso-PAF and
      phenylmethylsulfonyl fluoride. The amount of PAF increased for the first 30 min
      and declined thereafter. PAF resting levels were found low in the same cells.
      Furthermore, PAF-acetylhydrolase activity was determined in cell homogenates. The
      presence of metabolic products such as alkyl-phosphatidylcholine, alkyl- and
      alkenyl-phosphatidylethanolamine and alkyl-glycerol, as well as, its mono- and
      diacyl derivatives, indicates that FRTL5 cells and probably other thyroid cells,
      are very active in metabolizing PAF and lyso-PAF and suggests the co-operation of
      the corresponding metabolic pathways in these cells.

PMID- 9643363
TI  - Capillary electrophoresis to monitor the oxidative modification of low density
      lipoproteins.
AB  - A procedure has been developed that uses high performance capillary
      electrophoresis to monitor the changes in the electrophoretic mobility of low
      density lipoproteins (LDL) resulting from Cu2+-catalyzed lipid peroxidation.
      Using uncoated fused silica capillaries, methylglucamine-Tricine, pH 9.0, as
      electrophoresis buffer and a field strength of 350 V/cm, separation of native LDL
      and oxidized LDL could be achieved in 8-10 min. The electrophoretic mobility of
      native LDL under these conditions was 1.32 x 10(-4) cm2 x V(-1) x s(-1), and the
      migration time could be measured with a coefficient of variation of 0.44%. The
      increase in the electronegativity of LDLs during incubation with 10 microM Cu2+
      for 0.25-2.0 h resulted in a progressive increase in migration time. Monitoring
      the absorbance of the migrating LDL particles at a wavelength of 234 nm showed a
      progressive increase in peak area, which paralleled that in diene conjugation
      measured spectrophotometrically. Electronegative LDL particles formed by
      modification with malondialdehyde could also be separated from native LDL
      particles under these conditions. This new procedure should be useful in studies
      of factors influencing low density lipoprotein oxidation in vitro and in vivo.

PMID- 9643364
TI  - Identification of a heparin-binding domain in the distal carboxyl-terminal region
      of lipoprotein lipase by site-directed mutagenesis.
AB  - The interaction of lipoprotein lipase (LPL) with heparan sulfate proteoglycans
      plays an important role in the metabolism and catalytic function of the enzyme.
      We have used site-directed mutagenesis to replace the basic residues contained in
      a discontinuous charge cluster (residues Lys 321, Arg 405, Arg 407, Lys 409, Lys
      415, and Lys 416) of avian LPL with asparagine. The mutant proteins were
      expressed in Chinese hamster ovary cells and their affinity for heparin was
      evaluated by heparin-Sepharose chromatography. Mutation of residues Lys 321, Arg
      405, Arg 407, Lys 409, and Lys 416 resulted in a decrease in affinity for
      heparin. The triple mutant LPL(R405N, R407N, K409N) possessed almost no high
      affinity binding. The LPL mutants showed enzymatic activities ranging between 50
      100% of that seen for wild-type LPL demonstrating that the overall structure of
      the enzyme was not significantly altered by the mutations. Mutation of previously
      identified heparin-binding regions of LPL results in a relatively small decrease
      in heparin-binding affinity, as compared with mutations in this carboxyl-terminal
      region, indicating that Lys 321, Arg 405, Arg 407, Lys 409, and Lys 416
      constitute the major heparin-binding domain in LPL.

PMID- 9643365
TI  - Fluoride distribution in sound and carious root tissues of human teeth.
AB  - Proton probe analysis has been used to provide for the first time quantitative F
      concentration data in carious root tissues from subjects consuming water
      containing 1 ppm F. In small lesions at the neck of the tooth with minimal tissue
      loss the F concentration was significantly higher at the outer lesion edge than
      at the outer edge of adjacent sound root tissue. In one sample with high F values
      the lesion edge had 19,000 ppm F and the adjacent sound root surface 5,400 ppm F
      microg F/g apatite). In large lesions with extensive cavitation F was again
      concentrated in the outer edge of the lesion and was significantly higher (1,800
      4,100 ppm) than in adjacent sound inner dentine (190-290 ppm). Fluoride
      concentrations varied markedly along the outer edge of both normal and carious
      root tissues. Fluoride increase at the lesion edge is not an effect of tissue
      shrinkage but probably a result of remineralisation events during caries. This
      additional F may be expected to increase tissue resistance to further acid
      attacks.

PMID- 9643366
TI  - Detection, diagnosing, monitoring and logical treatment of occlusal caries in
      relation to lesion activity and severity: an in vivo examination with
      histological validation.
AB  - The aims of the present study were to investigate the ability of 3 experienced
      clinicians to detect occlusal carious lesions, assess their depth, diagnose their
      activity and define a logical management for each lesion. The material consisted
      of 35 third molars scheduled for extraction or surgical removal making it
      possible to validate the accuracy of the clinical recordings histologically.
      Examinations were carried out at baseline and after 4 months in order to monitor
      lesion progression. At the first visit a radiograph was taken; the number of
      filled surfaces was counted and the oral hygiene assessed generally and by
      disclosing occlusal plaque of the tooth under examination. After cleaning the
      occlusal surface caries was recorded in a selected investigation site using a
      visual ranked caries scoring system, as well as an electrical conductance
      recording (ECM). Apart from counting fillings and taking new radiographs the same
      procedure was performed at the second visit, which then was followed by
      extraction of the tooth. After sectioning the tooth lesion depth was recorded,
      and lesion activity, based on acid production, was assessed using methyl red dye.
      Lesion activity was also judged by means of polarized light microscopic
      examinations of the sections. Results showed strong relationships between the
      visual, ECM and radiographic assessments and both lesion depth and lesion
      activity. In contrast, all other parameters were poorly related to lesion
      activity. Changes in visual assessments and in conductance readings from first to
      second examination were poorly associated with lesion activity. In conclusion,
      clinicians are able to detect lesions, predict activity and severity and define a
      logical management of occlusal caries on the basis of a single examination.

PMID- 9643367
TI  - An in vitro system for the analysis of changes in depth distribution of
      diffusates in bacterial films.
AB  - No suitable technique exists which allows simultaneous analysis of time- and
      depth-dependent concentrations of all components of interest in single samples of
      intercellular fluid from dental plaque biofilms. We have developed an in vitro
      model which allows detailed study of these interactions by analysis of
      intercellular fluid and pH measurement at the film base. Compact, defined-depth
      films of Streptococcus mutans were formed in a micrometer-controlled, variable
      depth well and bathed in synthetic saliva. Films exposed to synthetic saliva
      containing glucose for 2 min followed by clearance with glucose-free synthetic
      saliva gave typical 'Stephan-type' pH profiles. Intercellular fluid isolated from
      successive 200-microm-thick sections of 600-microm-deep films was analysed by ion
      chromatography. A concentration gradient of lactate, falling with depth, was
      measured. The experimental system described here, the first of its type to be
      described, can easily be used to analyse pH changes and the depth-dependent
      distribution of diffusates in a model bacterial film. Although this bacterial
      film is far removed from a natural biofilm, the apparatus has potential for the
      study of grown biofilms and is an important advance towards position-dependence
      analysis of diffusates in biofilms.

PMID- 9643368
TI  - Dental caries susceptibility in mice is closely linked to the H-2 region on
      chromosome 17.
AB  - The generation of dental caries in humans is thought to be regulated by many
      intrinsic and social factors. In this study, we examined the effect of MHC on
      susceptibility to dental caries in mice. The mean carious score of BALB.K/Ola, a
      H-2 congenic strain in which the H-2 region derived from C3H/HeJ (H-2(k/k)) is
      introduced into BALB/cJ (H-2(d/d)), was markedly reduced as compared with that of
      its recipient strain (BALB/cJ). Mating experiments confirmed a strong genetic
      linkage between H-2 haplotype and caries susceptibility. These results
      demonstrate that one of the genetic factors of the susceptibility in the mouse is
      mapped within the H-2 region. This finding of a host genetic factor influencing
      the generation of dental caries will help in developing clinical preventive
      strategies.

PMID- 9643369
TI  - The effect of fluoridation on the occurrence of hidden caries in clinically sound
      occlusal surfaces.

PMID- 9643370
TI  - Programmed cellular response in radiation oncology.

PMID- 9643371
TI  - Effect of curdlan sulfate on the production of beta-chemokines and cytokines.

PMID- 9643372
TI  - Immunization with both T cell-dependent and T cell-independent vaccines augments
      HIV viral load secondarily to stimulation of tumor necrosis factor alpha.
AB  - Vaccination of HIV-infected individuals increases HIV viral load, reduces CD4
      cell counts, and might influence disease progression. Because these deleterious
      effects are postulated to be secondary to a direct activation of T lymphocytes
      induced by the immunogen, we compared immunologic and virologic effects of a T
      cell-dependent and a T cell-independent vaccine. Seventeen HIV-infected children
      were immunized with influenza (FLU) (T cell-dependent) or pneumococcal (PNEUMO)
      (T cell-independent) vaccines. HIV viral load and type 1 (IL-2 and IFN-gamma) and
      type 2 (IL-4 and IL-10) cytokine production were evaluated before and 7, 14, and
      28 days after vaccination. Slopes of CD4 cell counts analyzed 6 months before and
      6 months after vaccination were not significantly different. HIV viral load
      increased in both groups of children despite the fact that type 1 cytokine
      production and the type 1-to-type 2 ratio increased in FLU-vaccinated but not in
      PNEUMO-vaccinated patients. Thus, an increase in HIV viral load in the absence of
      T cell activation (as measured by cytokine production) was observed in PNEUMO
      vaccinated children. Because polysaccharides of the bacterial cell wall stimulate
      TNF-alpha production by monocyte-macrophages and TNF-alpha was shown to stimulate
      HIV replication directly on activation of NF-kappa b after binding the long
      terminal repeat (LTR) sequences of HIV, we measured TNF-alpha production and
      observed a significant increase in both groups of vaccines. These data suggest
      that an increase in HIV viral load can be observed in vaccinated HIV-infected
      children even independent of direct antigen-induced activation of T lymphocytes,
      and that augmented production of TNF-alpha might play a role in this phenomenon.

PMID- 9643373
TI  - Neutralizing antibodies directed against the V3 loop select for different escape
      variants in a virus with mutated reverse transcriptase (M184V) than in wild-type
      human immunodeficiency virus type 1.
AB  - The M184V substitution in human immunodeficiency virus type 1 (HIV-1) reverse
      transcriptase (RT) encodes high-level resistance to the (-)-enantiomer of 2',3'
      dideoxy-3'-thiacytidine (3TC) and low-level resistance to each of 2',3'
      dideoxycytidine (ddC) and 2',3'-dideoxyinosine (ddI). This mutation also results
      in decreased HIV replication fitness in primary cells, diminished RT
      processivity, and increased RT fidelity. To assess the effect of this
      substitution on genetic variation in the HIV env region, we cultured both M184V
      containing and wild-type BH10 in MT-4 cells in the presence of the neutralizing
      monoclonal antibody 447-52D, targeted to the GPGR epitope within the V3 loop of
      gp120. Outgrowth of viruses resistant to neutralization was followed by sequence
      analysis of the V3 loop by standard methodology. Wild-type HIV first showed
      escape after 15-22 days in culture. Sequence analysis revealed an arginine-to
      lysine change within the GPGR epitope in the V3 loop (R20K, AGA --> AAA) in six
      of six clones sequenced after day 36. In contrast, M184V-containing HIV first
      showed escape between days 25 and 32 and sequence analysis revealed an aspartate
      to-tyrosine change at amino acid 5 in V3 (N5Y; AAC --> TAC) in two of six clones
      at day 36 and in five of five clones at day 55. Similar results were obtained in
      two independent antibody selection protocols. The escape mutation in the wild
      type is consistent with the G --> A hypermutation observed in wild-type HIV-1,
      recently shown to cause an initial M184I change (before M184V) in 3TC-treated
      patients. In contrast, the N5Y substitution seen with M184V-containing HIV-1 is
      an A --> T transversion in V3.

PMID- 9643374
TI  - Cross-clade p17 peptide recognition by antisera to HGP-30, a 30-amino acid
      synthetic peptide antigen from HIV type 1 p17.
AB  - HGP-30, a 30-amino acid synthetic peptide analog of HIV-1SF2 p17 (aa 86-115), was
      used to immunize both mice and humans. Since the amino acid sequence of HGP-30 is
      relatively conserved among different HIV-1 strains and clades, experiments were
      carried out to determine if antisera obtained by immunizing animals and humans
      can recognize HGP-30-related peptide consensus sequences belonging to different
      clades. Results show that antisera from mice immunized with HGP-30 can recognize
      clade B and C and to a lesser degree clade A and E consensus sequences of HIV-1,
      in addition to recognizing HGP-30 sequence. The cross-clade recognition was
      higher in mouse sera obtained on day 42 than on day 14 or 28. MPL/SE and
      Novasomes were better adjuvants than alum in inducing antibodies that showed
      cross-clade recognition and IgG2a and IgG2b antibody isotypes. Similar cross
      clade recognition was observed in several sera from humans immunized with an HGP
      30/KLH/alum formulation. The human sera from HGP-30-immunized subjects evaluated
      for cross-clade recognition of HGP-30 peptides were from subjects whose cells
      showed significant protection from HIV infection on virus challenge in the hu-PBL
      SCID mouse model. These studies suggest that HGP-30 may be useful as a candidate
      vaccine antigen for populations in countries with prevalence of different HIV
      clades.

PMID- 9643375
TI  - Hypervariable epitope constructs representing variability in envelope
      glycoprotein of SIV induce a broad humoral immune response in rabbits and rhesus
      macaques.
AB  - Using synthetic peptides, we developed an approach to account for protein epitope
      variability. We have prepared, in a single synthesis, a cocktail of peptides we
      have designated a hypervariable epitope construct (HEC), which collectively
      represents much of the in vivo variability seen in an epitope. Eight HECs
      representing the in vivo variability seen throughout the envelope glycoprotein of
      the simian immunodeficiency virus (SIV) were designed and synthesized. The
      constructs were collectively conjugated to KLH (HEC-KLH) or recombinant gp130
      (HEC-rgp130) and used to immunize rabbits and rhesus macaques, respectively.
      Using sera collected from rabbits immunized with HEC-KLH, we demonstrated that
      individual components of the immunogen were recognized as antigen in ELISAs, and
      that the induced antibodies cross-reacted with several strains of SIV as well as
      with a strain of HIV-2. Following immunization of macaques with HEC-rgp130
      antiviral antibodies were induced. These antibodies were still present 9.5 months
      after the last boost and were also capable of recognizing several different
      strains of SIV, including SIVmac239, SIVmac251, and SIVsmH3, as well as a strain
      of HIV-2 (HIV-2ROD). In addition, the antibodies were also capable of
      neutralizing SIV viral infectivity in vitro. Peripheral blood lymphocytes (PBLs)
      from immunized macaques proliferated in response to whole proteins and virus.
      Finally, sera from monkeys immunized with SIV, rgp130, and HIV-2 as well as sera
      from HIV-2-positive humans recognized HECs in ELISAs, demonstrating the relevance
      of these epitopes in vivo. This approach can be used as an effective method for
      generating a strong, broadly cross-reactive humoral response against HIV and can
      serve as an important component of combination vaccines against HIV and AIDS.

PMID- 9643376
TI  - Administration of 9-[2-(phosphonomethoxy)propyl]adenine (PMPA) for prevention of
      perinatal simian immunodeficiency virus infection in rhesus macaques.
AB  - Simian immunodeficiency virus (SIV) infection of newborn macaques is a useful
      animal model to explore novel strategies to reduce perinatal human
      immunodeficiency virus (HIV) infection. The availability of two easily
      distinguishable virus isolates, SIVmac251 and the simian/human immunodeficiency
      virus chimera SHIV-SF33, allows tracing the source of infection following
      inoculation with both viruses by different routes. In the present study, we
      evaluated the efficacy of pre- and postinoculation treatment regimens with 9-[2
      (phosphonomethoxy)propyl]adenine (PMPA) to protect newborn macaques against
      simultaneous oral SIVmac251 and intravenous SHIV-SF33 inoculation. Untreated
      newborns became persistently infected following virus inoculation. When three
      pregnant macaques were given a single subcutaneous dose of PMPA 2 hr before
      cesarean section, their newborns became SIV-infected following SIV and SHIV
      inoculation shortly after birth. In contrast, when four newborn macaques were
      inoculated simultaneously with SIV and SHIV, and started immediately on PMPA
      treatment for 2 weeks, only one animal became persistently SIV-infected; the
      remaining three PMPA-treated newborns, however, had some evidence of an initial
      transient virus infection but were seronegative and healthy at 8 months of age.
      Our data demonstrate that PMPA treatment can reduce perinatal SIV infection and
      suggest that similar strategies may also be effective against HIV.

PMID- 9643377
TI  - Administration of interleukin 13 to simian immunodeficiency virus-infected
      macaques: induction of intestinal epithelial atrophy.
AB  - Increase Th2 cytokine production may contribute to some clinical manifestations
      of HIV infection, and studies have suggested that IL-13 rather than IL-4 is
      involved in these conditions. We directly tested this hypothesis by
      administrating IL-13 to SIV-infected macaques. SIV-infected rhesus macaques
      received a daily subcutaneous injection for 21 days of either IL-13 (10
      microg/kg/day) or a placebo. The four macaques treated with IL-13 experienced
      body weight loss (9.95 +/- 0.71%) related to intestinal tract damage: they all
      suffered from a complete atrophy of duodenal villi. This was presumably due to
      premature epithelial cell death: proliferating Ki67+ cells in glandular crypts
      were as numerous as in control animals, but many epithelial cells developed
      apoptosis. The duodenal mucosa was infiltrated with cells expressing CD56 and
      PEN5, two markers of NK cells, and there was a deregulation of local cytokine and
      chemokine production characterized by a decrease in IL-10 gene expression (25% of
      controls) and an increase in gene expression for IFN-gamma (4-fold control), MIP
      1alpha (8-fold control), and MIP-1beta (13-fold control). Thus, IL-13 can induce
      digestive epithelial cell injury in vivo in primates infected with a retrovirus.
      Therefore, its role should be considered in digestive manifestations of HIV
      infection as well as in other disorders associated with intestinal epithelial
      atrophy.

PMID- 9643378
TI  - Phylogenetic analysis of SIV and STLV type I in mandrills (Mandrillus sphinx):
      indications that intracolony transmissions are predominantly the result of male
      to-male aggressive contacts.
AB  - Natural SIVmnd and STLVmnd infections of mandrills in a colony at the Centre
      International de Recherches Medicales de Franceville (CIRMF) in Gabon were
      investigated by genetic analysis to determine the extent of intracolony
      transmission. SIVmnd pol sequence analysis indicates that the six strains present
      in the colony belong to the SIVmnd lentivirus subgroup previously defined
      according to the only available prototype sequence (SIVmndGB1), which originated
      from the same colony. The intraanimal nucleotide diversity (1.1-3.1%) was similar
      in range to that reported in individuals infected by other HIV/SIVs. The
      interanimal diversity (0.5-4.3%) was not significantly different from that
      observed in each individual mandrill, indicating an epidemiological link among
      the SIVmnd isolates of distinct animals within the colony. Phylogenetic analysis
      of these isolates, together with seroepidemiological and behavior surveillance
      within the colony, indicates a predominant male-to-male transmission of SIVmnd
      that probably occurred during bouts of interanimal aggression. Moreover, our
      results suggest one case of vertical transmission of SIVmnd from a naturally
      infected founder female to one of her six offspring. The first genetic analysis
      of STLV isolates from mandrills is also reported here. Partial tax/rex sequences
      were used to evaluate the diversity between seven STLVmnd isolates and their
      phylogenetic relationships with other known strains of human and nonhuman primate
      T cell leukemia virus, types I and II (PTLV-I/II). They all belong to the PTLV-I
      subtype, but two genetically distinct STLVmnd groups were evidenced within the
      mandrill colony. The phylogenetic analyses of the STLVmnd isolates, together with
      seroepidemiological and behavior surveillance of the mandrills, indicate that
      intracolony transmissions of STLVmnd are also predominantly the result of male-to
      male aggressive contacts.

PMID- 9643379
TI  - Lessons from the cat: feline immunodeficiency virus as a tool to develop
      intervention strategies against human immunodeficiency virus type 1.

PMID- 9643380
TI  - Variation in HIV type 1 V3 region env sequences from Mozambique.

PMID- 9643381
TI  - HIV type 1 env subtype A variants in Taiwan.

PMID- 9643382
TI  - Genomic sequence of HIV type 1 from four members of the Sydney Blood Bank Cohort
      of long-term nonprogressors.

PMID- 9643384
TI  - Introduction: Legionnaires' disease.

PMID- 9643383
TI  - Genetic and phylogenetic analysis of HIV type 1 strains from southern Ghana.

PMID- 9643385
TI  - Legionnaires' disease: clinical, epidemiological, and public health perspectives.
AB  - Legionnaires' disease is a modern environmental infectious disease. It stems from
      the capacity of the causative agent, Legionella, to multiply within amoebae in
      warm water and the use, during the 20th century, of devices that maintain water
      at warm temperatures and produce aerosols. When contaminated with Legionella,
      aerosols consisting of respirable droplets place the bacteria in juxtaposition
      with alveolar macrophages, which, as with amoebae, they may parasitize, resulting
      in illness in susceptible persons. The disease is much more common than
      previously appreciated with at least 13,000 cases estimated to occur per year in
      the United States, based on prospective studies. Two highly specific tests,
      urinary antigen detection and sputum culture, are available for diagnosis during
      illness. With 60% to 80% sensitivity, urinary antigen tests rapidly detect
      antigens of Legionella pneumophila serogroup 1, which are responsible for 70% of
      the cases of legionnaires' disease; results can be available within a few hours.
      Culture of sputum is 50% to 60% sensitive, but several days are required for
      growth, and many patients do not produce sputum. Serologic testing, although
      useful for epidemiologic studies when convalescent-phase antibody titers can be
      compared with acute-phase titers, is not helpful for clinical decision making
      because of the low positive predictive value of commercially available acute
      phase serologic tests. Erythromycins, intravenous azithromycin, and levofloxacin
      are currently approved by the US Food and Drug Administration for treatment of
      legionnaires' disease. However, clarithromycin and several other fluoroquinolones
      are active against Legionella and may also provide effective therapy. Recent
      recommendations from the Centers for Disease Control and Prevention's Hospital
      Infection Control Practices Advisory Committee should be helpful in reducing
      nosocomial legionnaires' disease. Recommendations are in place or are being
      developed to minimize the risk of disease in a variety of other settings.

PMID- 9643386
TI  - Classification of the genus Legionella.
AB  - There are currently 42 described species of legionellae representing 64
      serogroups in the family Legionellaceae and the genus Legionella. The phenotypic
      characteristics of legionellae are described, including growth requirements, and
      biochemical characteristics. Identification of legionellae by biochemical tests,
      fatty acid analysis, ubiquinones, protein profiles, carbohydrate analysis,
      serology, monoclonal antibodies, and molecular techniques is described. The
      occurrence and description of Legionella-like amebic pathogens are discussed. The
      problems of identification to the species level are discussed, along with the
      need for further evaluations of additional strains from all known species using
      biochemical and molecular techniques.

PMID- 9643387
TI  - Immunologic response and pathophysiology of Legionella infection.
AB  - Legionella pneumophila, the causative agent of legionnaires' disease, is a gram
      negative pleomorphic bacillus and fastidious in its growth in artificial medium.
      These bacteria grow readily intracellularly, including growth in macrophages and
      other phagocytic cells. Humoral antibodies develop readily to these bacteria not
      only in infected patients, but also in persons who have had subclinical exposure.
      High-levels of serum antibodies may also occur in individuals who recover from
      infection. However, cell-mediated immunity based on lymphocytes reacting with the
      organisms and cytokines produced by such lymphocytes are important in resistance.
      Vaccines prepared from killed Legionella or their components readily induce cell
      mediated immunity. Immune resistance to disease depends on lymphocyte-based
      immunity, activating cytokine formation, some of which activate macrophages to
      resist infection. Resistance to Legionella infection by experimental animals such
      as mice correlates with activation of macrophages, which can inhibit replication
      of the bacteria. Much recent experimental work has involved studies using inbred
      animals, including inbred mice genetically resistant to Legionella versus mice
      genetically susceptible. Detailed studies show that regulation of macrophage
      resistance versus susceptibility to infection is mediated by specific genetic
      mechanisms. Induction of cytokines by Legionella can activate immune cells,
      especially helper T cells. Th 1 type helper cells that produce type 1 class
      cytokines, such as interferon gamma and interleukin-2 (IL-2), are known to be
      important in cellular immunity to Legionella as well as to other opportunistic
      intracellular bacteria. In contrast, Th 2 type helper cells, which secrete type 2
      class cytokines such as IL-4, IL-5, and IL-6, activate B lymphocytes to produce
      humoral antibodies important in resistance to extracellular bacteria which
      secrete toxins and extracellular factors as compared to intracellular bacteria
      such as Legionella. Although Legionella, similar to other ubiquitous
      opportunistic pathogens, can cause serious infection in immunocompromised
      individuals, these bacteria have many distinguishing characteristics, such as
      very rapid replication in macrophages from susceptible individuals. However,
      activated macrophages restrict the growth of these bacteria. Infection by
      Legionella, if recognized clinically, can be readily treated with appropriate
      antibiotics. Currently, many studies are in progress concerning the mechanism of
      pathogenicity and assessment of the molecular biologic mechanisms of protective
      immune responses to this bacterium, which causes serious infection in
      immunocompromised individuals.

PMID- 9643388
TI  - Radiological manifestations of Legionella/Legionella-like organisms.
AB  - The chest radiograph of Legionellosis has been described in many reports.
      Although some attempted to describe patterns which are specific for Legionella,
      in fact, the roentgenographic findings in Legionella infection vary widely and
      depend largely on when in the course of illness the radiograph is obtained.
      Certain temporal characteristics, however, can serve to enhance the likelihood of
      the diagnosis of Legionella pneumonitis. Initial focal infiltrates are most
      commonly poorly marginated with 10% presenting with concomitant pleural effusion.
      The infiltrates often spread to contiguous lobes eventually becoming bilateral,
      with incidence of pleural effusions reaching 35%. This progression often occurs
      despite appropriate antimicrobial therapy and often in the face of clinical
      improvement. A similar pattern of progression also occurs in immunocompromised
      individuals; in addition, a high rate of cavitation and hilar adenopathy is seen
      in this subset of patients. A prolonged resolution phase of up to 6 months is
      common with rare development of residual densities. Correlating radiographic
      features with disease severity and mortality have largely been unsuccessful.

PMID- 9643389
TI  - Clinical features of legionnaires' disease.
AB  - Legionnaires' disease is a systemic infectious disease primarily involving the
      lungs, with multisystemic extrapulmonary manifestations. Any species of
      Legionella may cause legionnaires' disease in normal and compromised hosts. The
      clinical diagnosis of legionnaires' disease may be made on the basis of
      associated extrapulmonary clinical and laboratory findings. Although no single
      finding in legionnaires' disease is pathognomonic, the association of key
      extrapulmonary constitutes a typical pattern that is diagnostically
      characteristic. The syndromic approach based on a weighted point evaluation
      system described in the article gives physicians a system to arrive at a rapid
      presumptive clinical diagnosis of legionnaires' disease. Definitive diagnosis of
      legionnaires' disease is by direct fluorescent antibody testing of respiratory
      specimens, serological methods, Legionella urinary antigenuria, or culture.

PMID- 9643390
TI  - Legionella and immunosuppression.
AB  - Patients with defective immune systems are susceptible to Legionella infection,
      especially when the defect involves cell-mediated immunity. Thus, acquired immune
      deficiency syndrome (AIDS), corticosteroid administration, and hairy cell
      leukemia are risk factors for Legionellosis. Patients who have AIDS may be at
      risk for relapsing infections. Corticosteroid administration appears to
      predispose patients to simultaneous infection with multiple strains of
      Legionellae and development of lung abscess. Legionellosis also is found in
      patients who have humoral immune defects, but to a lesser extent. Thus, multiple
      myeloma, chronic lymphocytic leukemia, and chronic granulomatous disease have all
      been complicated by Legionella infection, although the risk seems to be minimal.

PMID- 9643391
TI  - Legionella: a major opportunistic pathogen in transplant recipients.
AB  - Legionella have a predilection for infecting immunocompromised patients, and
      transplant recipients have the highest risk. Legionella spp have been the most
      common cause of nosocomial pneumonia among transplant recipients at selected
      medical centers. Diagnosis is dependent on the ability of the clinical
      microbiology laboratory to isolate the organism by culture; therefore, the
      disease is easily overlooked. The mode of transmission of Legionella pneumophila
      is likely aspiration in transplant recipients. Clinical manifestations are
      similar to that of other bacterial pneumonias, although diarrhea is often
      prominent. The quinolone antibiotics (especially ciprofloxacin) are the
      antibiotics of choice because, unlike the macrolides or rifampin, they do not
      interact with the immunosuppressive agents used to counter rejection. Prevention
      of nosocomial legionellosis involves disinfection of the hospital's potable water
      system. Effective disinfection methods include superheat and flush or copper
      silver ionization; hyperchlorination is no longer recommended. Routine culture
      surveillance directed at the hospital water supply for Legionella is mandatory in
      hospitals caring for transplant patients.

PMID- 9643392
TI  - Treatment of legionnaires' disease.
AB  - Erythromycin has been the most commonly used drug for the treatment of
      legionnaires' disease; however, failures have occurred and adverse effects are
      common. Doxycycline intravenously is preferred and is less expensive. The newer
      macrolides/azalides, clarithromycin and azithromycin, have excellent in vitro
      activity against Legionella and fewer adverse effects than erythromycin. The
      fluoroquinolones, particularly levofloxacin, are the most active anti-Legionella
      antibiotics available. Other agents with activity against Legionella pneumophila
      include minocycline, rifampin, and trimethoprim-sulfamethoxazole. The preferred
      therapy of legionellosis in immunocompromised patients are quinolone/macrolide
      combinations, eg, levofloxacin plus azithromycin.

PMID- 9643393
TI  - Disinfection of water distribution systems for Legionella.
AB  - Hospital-acquired legionnaires' disease arises from the presence of Legionella in
      hospital water systems. Legionella not only persists in hot water tanks but is
      also found in the biofilm throughout the entire water distribution system.
      Conditions within water systems that promote Legionella colonization include
      water temperature, configuration and age of the hot water tank, physicochemical
      constituents of the water, plumbing materials, and commensal microflora. Hospital
      acquired legionnaires' disease has been prevented by instituting control measures
      directed at the water distribution system. These include superheat-and-flush,
      copper/silver ionization, ultraviolet light, instantaneous heating systems, and
      hyperchlorination. Each of the above disinfection methods has been proven to be
      effective in the short-term, but long-term efficacy has been difficult due to
      limitations associated with each method. The complexities of Legionella
      disinfection, including advantages and disadvantages of each method, are
      reviewed. A successful Legionella prevention program requires cooperation and
      communication among hospital administrative personnel, engineers, and infection
      control staff. Routine environmental surveillance cultures for Legionella are the
      critical component for successful long-term disinfection. Culture results
      document the efficacy of the disinfection method and alert the hospital staff to
      consider Legionella in hospitalized patients with pneumonia.

PMID- 9643394
TI  - Diagnostic case study: Rasmussen aneurysm.

PMID- 9643395
TI  - Research in progress.

PMID- 9643396
TI  - Pregnancy and epilepsy.
AB  - Pregnant women with epilepsy are at risk for a variety of complications. This
      article reviews the extensive literature on pregnancy and epilepsy with special
      emphasis on the management of pregnancy. Information is presented concerning
      seizure frequency in pregnancy, effects of epileptic seizures on the fetus,
      occurrence of complications during pregnancy and delivery, the incidence of fetal
      congenital malformations, and infant development. Recommendations are given
      concerning prenatal counseling, antiepileptic drug management, breast feeding,
      vitamin K supplementation and folic acid supplementation.

PMID- 9643397
TI  - Outborn status with a medical neonatal transport service and survival without
      disability at two years. A population-based cohort survey of newborns of less
      than 33 weeks of gestation.
AB  - OBJECTIVE: Prenatal events are thought to play an important role in long-term
      handicap, but the specific role of perinatal factors remains controversial. Our
      study, conducted in the context of this debate, aimed to break down the various
      components of perinatal management and to assess the relationship between these
      components and survival without disability at the age of two years. STUDY DESIGN:
      A prospective geographically-defined study was conducted in 1985 in the Paris
      metropolitan area. It covered 53430 births (stillbirths and live births),
      including 539 that occurred between 25 and 32 weeks gestation. The relationship
      between perinatal management and survival without disability was studied by a
      multivariate analysis (logistic regression). The analysis was restricted to a
      group of 202 infants born at 31 or 32 week's gestation, to avoid indication bias.
      RESULTS: An inborn status (delivery in a tertiary care facility) exerted a
      protective effect on survival without disability at the age of two years
      (Adjusted Odds Ratio (OR)=7.51 [1.51; 37.4]), even though the area we studied
      possessed an excellent Medical Neonatal Transport Service. Multiple pregnancies
      also seemed to have a protective effect (Adjusted OR=2.45 [0.96; 6.27]). No
      statistically significant association was seen between survival without
      disability at two years and the presence of a hospital staff paediatrician in the
      delivery room. CONCLUSION: These results lead us to consider what the concept of
      inborn/outborn represents in the perinatal management of infants at high risk.

PMID- 9643398
TI  - Ante- and intrapartum diagnosis of vasa praevia in singleton pregnancies by
      colour coded Doppler sonography.
AB  - Vasa praevia is a rare complication of pregnancy associated with a high fetal
      morbidity and mortality. As planned caesarean section can circumvent fetal risks,
      early detection of vasa praevia is desirable. Antenatal diagnosis by ultrasound
      by visualisation of vasa praevia may be difficult by transvaginal sonography
      alone due to an unfavourable angle of insonation. Combination of transabdominal
      and transvaginal sonography is superior in imaging the placental type, location,
      insertion of the cord and vasa praevia. We present four cases of antepartum and
      one case of intrapartum diagnosis of vasa praevia in singleton pregnancies using
      transabdominal and transvaginal colour coded Doppler sonography. A bipartite
      placenta with normal cord insertion was found in three cases and with velamentous
      insertion of the cord in one case. One case had a partially membranous placenta
      with velamentous insertion of the cord. From the site of cord insertion fetal
      vessels were coursing over the internal cervical os and then continued in an
      amniotic sheet to the main placental mass on the opposite uterine wall.

PMID- 9643399
TI  - Umbilical blood flow and neonatal morphometry: a multivariate analysis.
AB  - OBJECTIVE: To study the relation between the state of umbilical blood flow and
      neonatal morphometry. STUDY DESIGN: We have recorded data from 460 pregnant
      women. Umbilical systolic to diastolic ratio was measured within the 3 days prior
      to the birth. Weight, height, head and chest circumferences, ponderal and head to
      chest circumferences ratio were considered for the study. RESULTS: In a
      univariate analysis, the best correlated variable to S/D ratio was the weight (r=
      0.35). However, a forward stepwise multiple regression analysis demonstrated that
      the best predictors of S/D ratio were height and ponderal index. Small-for
      gestational-age fetuses with placental insufficiency (n=20) had a significant
      more pronounced decrease of weight, height, head circumference and chest
      circumference than those with normal placental perfusion (n=31). The degree of
      decrease of ponderal index and HC/TC was similar in both groups. CONCLUSIONS:
      Umbilical blood flow is one important factor determining newborn morphometry. If
      only one growth variable is considered, the best correlation with umbilical S/D
      ratio is found to be the weight. The multivariate regression analysis concluded
      that the two most influential factors by umbilical blood flow are height and
      ponderal index and the rest of the morphometric parameters lost their significant
      correlations when adjusted by these variables. The impairment on neonatal
      morphometry in small-for-gestational-age fetuses associated to placental
      insufficiency is more severe than that with normal placental perfusion. However,
      it does not have a more pronounced decrease of ponderal index than the rest of
      causes of small-for-gestational-age fetuses.

PMID- 9643400
TI  - Does increased resistance on umbilical artery Doppler preclude a trial of labour?
AB  - OBJECTIVE: To determine whether patients with increased resistance on umbilical
      artery Doppler velocimetry could be safely allowed a trial of labour. DESIGN: The
      Coombe Womens' Hospital is a university teaching hospital which takes tertiary
      referrals. All singleton pregnancies found to have increased resistance (>2 SD
      above the mean for gestational age) on umbilical artery Doppler ultrasound
      between 1993 and 1995 inclusively were identified from the ultrasound database
      and reviewed, retrospectively. Cases where the umbilical artery waveform reverted
      to normal or deteriorated to absent end diastolic flow on a subsequent scan were
      excluded. The 118 cases identified were divided into two groups, those that were
      delivered by elective caesarean section and those that laboured. RESULTS: Forty
      five patients were delivered by elective caesarean section and 73 were allowed to
      labour. In the group that laboured over 90% delivered vaginally and 9.8% were
      delivered by emergency caesarean section. Three babies had a cord pH less than
      7.20 in the group that laboured. Two babies had an Apgar score of less than 7 at
      5 min in the group that were delivered electively. There were no neonatal
      seizures or perinatal deaths in either of the two groups. CONCLUSIONS: This study
      shows that patients with increased resistance on umbilical artery Doppler can be
      allowed a trial of labour without compromising the fetal outcome. We would
      suggest that consideration be given to induction of labour in selected patients
      as an alternative to elective section.

PMID- 9643401
TI  - Application of guidelines for occupational HIV infection control during delivery
      in Italy.
AB  - OBJECTIVE: We surveyed the attitudes of Italian obstetricians toward the
      application of HIV infection control guidelines during labour and delivery
      proposed by the Italian National Committee for HIV Infection. STUDY DESIGN: We
      identified 66 obstetric centres affiliated to the AOGOI (Association of Italian
      Gynecologists and Obstetricians). A postal questionnaire was sent to 752
      physicians in charge in the centres. RESULTS: A total of 419 clinicians (55.7%)
      completed and returned the form to the coordinating centre. Obstetricians were
      directly asked about the need for routine adoption of the Italian guidelines for
      delivery of women with positive or unknown HIV status (indicating the routine use
      during delivery of protective glasses, impermeable garments, mask and sterile
      latex gloves, the washing of hands with detergent solution after using gloves and
      collection of needles and sharp instruments in suitable containers). A total of
      319 (76.1%) clinicians agreed that all these procedures should be adopted. In
      clinical practice, however, obstetricians declared that the use of latex gloves
      and collecting needles in suitable containers were always adopted, 'washing hands
      after using gloves' less frequently, and other procedures such as protective
      impermeable garments, glasses and mask were infrequently applied.

PMID- 9643402
TI  - Outcome of 88 pregnancies with absent or reversed end-diastolic blood flow (ARED
      flow) in the umbilical arteries.
AB  - OBJECTIVES: To investigate both perinatal and postneonatal morbidity and
      mortality in fetuses with absent or reversed end-diastolic flow (ARED flow) in
      the umbilical artery. STUDY DESIGN: A 5 year prospective follow-up of 88 fetuses
      with ARED flow. RESULTS: Sixteen stillbirths, 16 neonatal deaths, six
      postneonatal deaths and one death at 2 years of age were noted. Out of the 42
      fetuses born alive, 36 showed a normal neurological development whereas six were
      mentally handicapped. Adverse prognosis was more frequently found in the group
      with absent end-diastolic flow at first examination and then reversed flow until
      delivery, compared to the groups of always absent or always reversed end
      diastolic flows. CONCLUSIONS: Prompt delivery is recommended in these high-risk
      pregnancies in order to prevent long-term sequelae, obviously depending on the
      local limits of viability. Further studies appropriately designed for assessing
      long-term neurodevelopment of fetuses with ARED flow, although demanding, are
      mandatory.

PMID- 9643403
TI  - Role of uterine artery Doppler investigation in pregnant women with chronic
      hypertension.
AB  - OBJECTIVE: To evaluate the role of uterine artery Doppler investigation in
      predicting perinatal outcome of patients with chronic hypertension. STUDY DESIGN:
      Uterine artery velocimetry was investigated at 24 weeks gestation in 78 chronic
      hypertensive pregnant women by means of color Doppler. The resistance index (RI)
      and the presence of a diastolic notch were recorded and related to the
      development of superimposed preeclampsia (SPE), pregnancy aggravated hypertension
      (PAH). and intrauterine growth retardation (IUGR). RESULTS: There were more
      pregnancy complications in the 25 patients with abnormal RI, compared with the 53
      women with normal RI (SPE 12% vs. 0%, PAH 36% vs. 7% and IUGR 52% vs. 2%;
      P<0.01), and more in women with a bilateral diastolic notch compared with those
      without (SPE 23% vs. 0, PAH 54% vs. 4%, IUGR 85% vs. 2%; P<0.0001), while no
      differences were detected in those with only a unilateral notch, except for PAH
      (27% vs. 4%; P<0.01). CONCLUSION: Uterine artery Doppler velocimetry identifies a
      subgroup of chronic hypertensive patients with a high frequency of pregnancy
      complications.

PMID- 9643404
TI  - Women attending human immunodeficiency virus counselling and testing site because
      of pregnancy, and prevalence of newly diagnosed infections.
AB  - To evaluate the trend of and the reason for women attending HIV counselling and
      testing (CT) because of pregnancy or pregnancy planning, and the observed human
      immunodeficiency virus (HIV) prevalence rate, systematic data was gathered during
      free pre- and posttest discussion, at a major CT site of Rome, Italy, from July
      1985 to June 1996. A total of 3608 women were enrolled, increasing from 0.9% of
      the total number of female clients in 1986 to 34.6% in 1996. Most women (92.5%)
      were referred by gynaecologists, mostly without reported risk factors for HIV
      infection. In 22.5% of cases the test was performed after the first trimester of
      pregnancy. Prior tested women increased significantly from 6.7% in 1989 to 33.4%
      in the first half of 1996. Two thirds of women reported their current partners
      were not tested for HIV. Thirteen (0.36%) newly diagnosed women were observed;
      four were not aware of being at risk. In Italy HIV testing seems to have been
      included as a part of routine prenatal care. Efforts should be made to optimise
      the period when testing is performed. Universal counselling and testing of the
      couple could be the appropriate way to recognise most cases of newly diagnosed
      HIV infection.

PMID- 9643405
TI  - Confidential enquiry into maternal deaths in The Netherlands 1983-1992.
AB  - OBJECTIVE: To determine the causes of maternal death in The Netherlands. STUDY
      DESIGN: Nationwide Confidential Enquiry into the Causes of Maternal Deaths during
      the period 1983-1992. RESULTS: Of 192 direct and indirect maternal deaths, 154
      (80%) were available for the Enquiry. The most frequent direct causes were (pre
      )eclampsia, thrombo-embolism, obstetrical haemorrhage and sepsis. Cerebro- and
      cardiovascular disorders were the most frequent indirect causes of death. Age
      above 35 years and parity 3 or more are related to higher maternal mortality.
      Women from non-caucasian origin are more prone to death in comparison to
      caucasian women. Autopsy was performed in 88 cases (57%). Of the 24 women where
      labour started at home, the place of birth played a significant role in delay in
      four. CONCLUSIONS: More efforts should be made to have a higher percentage than
      80% available for the Confidential Enquiry as in the UK where only 1-4% of deaths
      are not available for similar purposes. Also, the autopsy rate of 57% is much
      lower than in the UK (82%). Special strategies should be developed to improve
      maternal health of populations at higher risk such as women of high age and
      parity and immigrant populations.

PMID- 9643406
TI  - Thermal balloon endometrial ablation: safety aspects evaluated by serosal
      temperature, light microscopy and electron microscopy.
AB  - OBJECTIVES: Thermal balloon endometrial ablation is a new method for treating
      menorrhagia. The technique appears to be less difficult compared to standard
      hysteroscopic ablation techniques and to be significantly safer. The influence
      into the uterine wall of the thermal balloon ablation procedure was investigated
      with special reference to the ability of total destruction of the endometrium and
      the thermal action on the myometrium and the serosa. STUDY DESIGN: Temperatures
      were measured at the uterine serosal surface during thermal balloon endometrial
      ablation for 8-16 min in eight patients. After subsequent hysterectomy the extent
      of thermal damage into the myometrium was assessed by light and electron
      microscopy. RESULTS: The highest temperature measured on the uterine serosa was
      39.1 degrees C. Coagulation of the myometrium adjacent to the endometrium could
      be demonstrated by light microscopy in all patients, with a maximum depth of 11.5
      mm. By electron microscopy no influence of heat could be demonstrated beyond 15
      mm from the endometrial surface. CONCLUSION: Up to 16 min of thermal balloon
      endometrial ablation therapy can destroy the endometrium and the submucosal
      layers. The myometrium is only coagulated to a depth where full thickness
      necrosis or injury is unlikely.

PMID- 9643407
TI  - Uterine papillary serous carcinoma: study of 19 cases.
AB  - OBJECTIVE: Uterine papillary serous carcinoma (UPSC) is an uncommon highly
      malignant variant of endometrial carcinoma that histologically and clinically
      resembles ovarian papillary serous carcinoma. The purpose of this study was to
      present the conjoined experience of two regional hospitals in the south of Israel
      (Soroka Medical Center, Beer-Sheva and Kaplan Hospital, Rehovot) of handling this
      tumour. STUDY DESIGN: Data from the files of 19 patients with UPSC who were
      managed at these hospitals between July 1991 and June 1997 were evaluated.
      RESULTS: The three-year survival rate was 57.3% overall; 83.3% for Stage I and
      21.2% for Stages II, III, and IV combined (P<0.02). Eighteen patients had primary
      surgery which included total abdominal hysterectomy and bilateral salpingo
      oophorectomy and 15 (83.3%) of them received postoperative adjuvant therapy which
      included radiotherapy and/or systemic chemotherapy. CONCLUSIONS: The prognosis of
      patients with UPSC is worse than that of patients with other forms of endometrial
      carcinoma. Primary surgery comprised of total abdominal hysterectomy, bilateral
      salpingo-oophorectomy and staging is the mainstay of treatment. The type of
      postoperative treatment is not consistent. By and large, adjuvant pelvic
      radiotherapy is usually given in early-stage disease and adjuvant systemic
      chemotherapy is usually prescribed in advanced-stage disease.

PMID- 9643408
TI  - Estrogen and postmenopausal estrogen/progestin therapy: effect on endothelium
      dependent prostacyclin, nitric oxide and endothelin-1 production.
AB  - It is well documented that postmenopausal estrogen/progestin therapy (HRT)
      protects women against cardiovascular disorders. However, the mechanism(s) by
      which this protection is mediated remains largely unresolved, because beneficial
      effects of estrogen on the blood lipid profile account for only 20-30% of the
      overall protection. Growing evidence suggests that estrogen has direct effects on
      the blood vessel wall indicating that vascular endothelium may play a key role in
      mediating these effects by producing vasoactive factors, such as prostacyclin
      (PGI2), nitric oxide (NO) and endothelin-1 (ET-1). In vitro estrogen stimulates
      endothelial PGI2 and NO production, whereas ET-1 production is not affected.
      Moreover, in vivo studies indicate that estrogen and HRT increase PGI2 and NO
      production, whereas ET-1 production decreases. These effects are evidently
      mediated through estrogen receptors in endothelial cells. Thus, estrogen and HRT
      lead to the dominance of vasodilatory and antiaggregatory agents released by the
      endothelial cells. This may be an important new mechanism in the cardiovascular
      protection mediated by estrogen and HRT.

PMID- 9643409
TI  - Conservation of the follicular population in irradiated rats by the
      cryopreservation and orthotopic autografting of ovarian tissue.
AB  - AIM: To preserve the follicular population in rats prior to abdominal irradiation
      by the orthotopic autografting of ovarian cortical slices (frozen/thawed) in one
      of two cryoprotective agents (CPAs). The proportion of follicular survival will
      be quantified at autopsy and a comparison will be made of the two CPAs. METHOD:
      Thirty Wistar rats, aged 38-39 days, were unilaterally ovariectomised. The
      ovaries of twenty animals were slow-cooled in either 1.5 M dimethylsulphoxide
      (DMSO; group B) or 1.5 M ethylene glycol (EG; group C). The ovaries of the
      remaining ten animals (group A) were fixed and histologically examined to
      determine a fresh follicle count. The contralateral ovary was irradiated with a
      single dose of 2.5 Gy. Frozen tissue (from groups B and C) was thawed rapidly and
      autografted into the irradiated ovarian bursa. All animals were mated eighteen
      days after grafting and were sacrificed eighteen days later. At autopsy, the
      number of embryos was counted and the ovarian weights recorded, before the tissue
      was prepared histologically for quantification of follicular survival. RESULTS:
      There was no significant difference in the pregnancy rate in the three groups
      and, although there was a higher number of embryos in the irradiated control
      group A compared with groups B and C, the difference was not significant. The
      follicle count in groups B and C was significantly higher than in group A. In
      group A, the percentage of growing follicles was higher than in groups B and C
      and the fresh ovary. CONCLUSIONS: Autografting frozen/thawed ovarian tissue
      preserved a proportion of the follicular population in irradiated rats. There was
      no significant difference in the numbers of follicles surviving cryopreservation
      in the two CPAs. Since the irradiated rats were not totally sterilised, we cannot
      conclude that cryopreserved grafts can restore fertility.

PMID- 9643410
TI  - Cervical pregnancy managed by suction evacuation and balloon tamponade.
AB  - A woman with a very poor obstetric history with a cervical pregnancy was managed
      without hysterectomy. Diagnosis was made by the transvaginal ultrasound.
      Haemorrhage was controlled by suction evacuation and balloon tamponade. Although
      cervical perforation occurred, the tamponade was able to control haemorrhage
      after repair of the perforation.

PMID- 9643411
TI  - Delayed recognition of major vascular injury during laparoscopy.
AB  - We report an unusual case of left common iliac artery and vein injury during
      laparoscopy. The injury was recognized 3 h after the completion of the
      laparoscopy. The patient was promptly treated by explorative laparotomy and
      repair of the lacerated vessels. Major vascular injury during laparoscopy is
      usually caused by the Verres needle or the first laparoscopic trocar. Failure to
      recognize the injury during the laparoscopic procedure itself can be attributed
      to the intraperitoneal CO2 pressure compressing the bleeding vessels and to the
      decreased venous return caused by the steep Trendelenburg position. Major
      vascular injury should be recognized as early as possible since it is a life
      threatening condition that necessitates immediate and prompt treatment.

PMID- 9643412
TI  - Non-Hodgkin's lymphoma during pregnancy--case report.
AB  - Occurrence of Non Hodgkin's lymphoma (NHL) in pregnancy is very rare. A 24-year
      old woman with NHL stage IVB complicating pregnancy is presented. The diagnosis
      was made by biopsy at 27 weeks. The patient received combination chemotherapy
      which led to remission of the disease. The baby was delivered by an emergency
      caesarean section, due to fetal distress at 31 weeks. Unfortunately after a short
      period of remission a relapse occurred and magnetic resonance imaging (MRI)
      showed cerebral involvement, indicating a poor prognosis. She died seven months
      later from disseminated disease.

PMID- 9643413
TI  - Congenital cystic adenomatoid malformation of the lung and fetal hydrops--a case
      with favourable outcome.
AB  - We present a case of congenital cystic adenomatoid malformation of the lung
      (CCAM) diagnosed at 23 weeks of gestation with concomitant fetal hydrops. The
      sonographical picture of CCAM disappeared in the third trimester of pregnancy and
      fetal hydrops resolved under medication with digitalis to the mother. The neonate
      showed mild dyspnea; the prenatal diagnosis of CCAM was confirmed by chest X-ray
      and computed tomography. The affected lung segments were dissected at 5 days of
      age. The diagnosis of CCAM type III was confirmed histologically.

PMID- 9643414
TI  - Chorioangioma of the placenta in association with early severe polyhydramnios and
      elevated maternal serum HCG: a case report.
AB  - We report a case of a chorioangioma of the placenta which was associated with
      elevated maternal serum HCG in the second trimester, severe early polyhydramnios
      and premature delivery. Chorioangioma should be considered in the differential
      diagnosis of an elevated HCG observed as part of the triple test.

PMID- 9643415
TI  - Discordant prenatal diagnosis of congenital toxoplasmosis in a dizygotic
      pregnancy.
AB  - Prenatal diagnosis of toxoplasmosis gondii in twin pregnancies has been described
      twice. In both cases they were accomplished by prenatal blood sampling of the
      foetuses. We report the first prenatal diagnosis with a discordant result in a
      dizygotic pregnancy. One of the foetuses died in utero and the other was born
      unaffected at term.

PMID- 9643416
TI  - Renal venous thrombosis: an unusual cause of fetal distress.
AB  - Renal venous thrombosis (RVT) is a rare event in neonates and infants. Its
      incidence varies from 0.5 per thousand concerning admissions in neonatal
      intensive care units to 0.5% in autopsic findings. Some cases may occur in the
      antenatal period. Clinical presentation in infants includes a mass in the flank.
      hematuria and thrombocytopenia. We report a case of RVT which was diagnosed at 34
      weeks' gestation by ultrasound in a fetus showing cardiotocographic signs of
      fetal distress. We observed the typical pattern reported by pediatric
      radiologists: renal enlargement, loss of the cortico-medullary boundary, echoic
      streaks following the direction of interlobular veins, lack of definition of
      renal sinus echoes and loss of venous flow in the right kidney by Doppler
      velocimetry. After delivery by caesarean section and transient hyperbilirubinemia
      and moderately impaired renal function the infant weighing 2435 g had a full
      recovery at 1 week and a normal evolution at 1 month of life.

PMID- 9643417
TI  - The identification of myogenic cells in skeletal muscle, with emphasis on the use
      of tritiated thymidine autoradiography and desmin antibodies.
AB  - The identification of myogenic precursor cells (mpc) is a key factor in
      determining the early events in the myogenesis and regeneration of skeletal
      muscle. Although satellite cells have long been established as the providers of
      myoblastic cells, very little is really known (apart from their anatomical
      location in relation to muscle fibres and their ability to migrate) about the
      precise role of satellite cells in myogenesis. Numerous techniques for labelling
      mpc have been devised, but none of these has proven to be completely reliable in
      firmly establishing the origin of myogenic cells. The use of tritiated thymidine
      to label DNA in proliferating mpc (which are not specifically distinguishable at
      the time) and the subsequent location of their labelled progeny in myotube nuclei
      has revealed a great deal of data on the timing of myogenesis, but not about the
      nature of mpc themselves. DNA synthesis can also be detected by antibodies to the
      thymidine analogue, bromodeoxyuridine, and also by antibody staining for
      proliferating nuclear cell antigen. Like tritiated thymidine, these other markers
      are not specific for muscle but are general markers for DNA synthesis. In situ
      hybridisation of various muscle-specific genetic markers and their products has
      been informative, as has immunolabelling of myogenin, MyoD1 and desmin. Desmin
      labelling has been particularly instructive in identifying mpc because it is one
      of the first muscle-specific proteins to be produced in mpc. This review covers
      some of the techniques mentioned above and their usefulness in determining the
      early events in myogenesis.

PMID- 9643418
TI  - Differentiation of the epidermis during scale formation in embryos of lizard.
AB  - The formation of the first epidermal generations and in particular of the
      shedding complex in the developing scales of the lizards Anolis lineatopus and
      Podarcis muralis was studied by electron microscopy. The initially linear and
      bilayered epidermis turned into symmetric papillae, which became asymmetric
      scales. The outer periderm was more electrondense than the following layer,
      provisionally named 'inner periderm' but probably derived from the basal layer.
      Coarse thick filaments progressively filled the cytoplasm of the inner periderm
      or formed reticulate bodies resembling avian peridermal granules. Peridermal
      cells cornified slightly and could be shed in ovo. From the basal layer various
      suprabasal epithelial layers were produced. The first layer contained
      keratohyalin-like granules and was identified as a clear layer. Beneath it a
      spinulated (Anolis) or serrated (Podarcis) oberhautchen differentiated. The clear
      and 'oberhautchen' layers constitute the first shedding complex. The first
      epidermal layers that were shed consisted of flaking periderm or periderm
      together with the clear layer. The differentiation of a mesos layer was under way
      before hatching, when the epidermal morphology resembled a stage 4-5 of the adult
      shedding cycle. Fibroblasts under the inner side of the scale made few contacts
      with the basement membrane and their cytoplasmic elongations were mostly oriented
      parallel to the dense lamina. Instead, fibroblasts under the basal layer of the
      outer scale surface (BLOS) made numerous contacts with the basement membrane,
      suggesting that more dermal-epidermal interactions take place on this side of the
      scale.

PMID- 9643419
TI  - Fibre optic confocal imaging (FOCI) of keratinocytes, blood vessels and nerves in
      hairless mouse skin in vivo.
AB  - Fibre optic confocal imaging (FOCI) enabled subsurface fluorescence microscopy of
      the skin of hairless mice in vivo. Application of acridine orange enabled imaging
      of the layers of the epidermis. The corneocytes of the stratum corneum, the
      keratinocytes in the basal layers and redundant hair follicles were visualised at
      depths greater than 100 microm. Cellular and nuclear membranes of keratinocytes
      of the skin were visualised by the use of acridine orange and DIOC5(3). Imaging
      of the skin after injection of FITC-dextran revealed an extensive network of
      blood vessels with a size range up to 20 microm. Blood cells could be seen moving
      through dermal vessels and the blood circulation through the dermal vascular bed
      was video-taped. The fluorescent dye 4-di-2-ASP showed the presence of nerves
      fibres around the hair follicles and subsurface blood vessels. Comparison was
      made between images obtained in vivo using FOCI and in vitro scanning electron
      microscopy and conventional histology. FOCI offers the potential to study dynamic
      events in vivo, such as blood flow, skin growth, nerve regeneration and many
      pathological processes, in ways which have not previously been possible.

PMID- 9643420
TI  - Pancreatic endocrine cells in Bufo bufo: immunocytochemistry and ultrastructure.
AB  - The endocrine pancreas of the toad consists of rounded islets of various sizes
      embedded in the exocrine tissue. Isolated cells are also present. At least 4
      types of endocrine cell are distinguishable by shape, size and electrondensity of
      the secretory granules as well as by their immunoreactivity with different
      antisera: insulin, somatostatin, pancreatic polypeptide, and glucagon cells.
      Insulin cells can be divided into 2 types according to their cytoplasmic
      electrondensity. Colocalisation of different hormones in the same cell is rarely
      observed. The close contact between endocrine and exocrine cells and the scarcity
      of nerve supply is indicative of a paracrine control of hormone secretion.

PMID- 9643421
TI  - Muscle fibre types and their distribution in the biceps and triceps brachii of
      the rat and rabbit.
AB  - Muscle fibre type composition and distribution in the biceps brachii (long head)
      and triceps brachii (long head) of the rat and rabbit were investigated using the
      following histochemical techniques: myosin ATPase, with preincubation at pH 10.4
      and 4.35; succinate dehydrogenase (SDH) and glycogen phosphorylase. The muscle
      fibres were classified into slow-twitch (SO), fast-twitch glycolytic (FG), fast
      twitch oxidative glycolytic (FOG and FOg) and fast-twitch oxidative fibres (FO).
      Significant differences in the regional distribution of muscle fibre types have
      been observed between the rat and the rabbit. In the rat, SO fibres were
      restricted to the deep regions of both biceps and triceps brachii, whereas FG
      fibres were located in the intermediate and superficial regions (the superficial
      regions contained the highest percentages of FG fibres). In the rabbit, SO and FG
      fibres were spread over the entire muscle, although SO and FG fibres were most
      abundant in the deep and superficial regions respectively. These findings
      indicate that the biceps and triceps brachii are more regionalised in the rat
      than in the rabbit.

PMID- 9643422
TI  - Comparative skeletal muscle fibre morphometry among wild birds with different
      locomotor behaviour.
AB  - Six muscles of the mallard duck (Anas platyrhynchos), the common coot (Fulica
      atra) and the yellow-legged gull (Larus cachinnans) were analysed
      morphometrically, with special emphasis on their functional implications and
      physiological needs. Oxidative fibres always had significantly smaller size than
      anaerobic fibres, although no differences in the number of capillaries per fibre
      were found. This resulted in greater capillary counts per unit of fibre area and
      perimeter in oxidative than anaerobic fibres, which indicates that the greater
      demand for oxygen supply may be achieved by decreasing the size of the muscle
      fibre rather than by increasing the number of associated capillaries. Fast
      oxidative fibres of the pectoralis and the triceps of the gull had greater sizes
      than the fast oxidative fibres of the mallard and the coot, which correlates with
      the difference in energetic demands between flapping and gliding flight. Greater
      fibre cross-sectional areas and perimeters seem suited to afford the long-lasting
      activity with low metabolic demands required during gliding. By contrast,
      mallards and coots attain a high oxidative metabolism, during sustained flapping
      flight, by reducing fibre size at the expense of a diminished ability for force
      generation. Between-species comparisons of the hindlimb muscles only yielded
      differences for the anaerobic fibres of the gastrocnemius, as an important
      adaptive response to force generation during burst locomotion. The need to manage
      sustained swimming abilities effectively may result in similar FOG fibre
      morphometry of the hindlimb muscles studied, indicating that a compromise between
      the oxygen flux to the muscle cell and the development of power is highly
      optimised in oxidative fibres of the bird species studied.

PMID- 9643423
TI  - Immunofluorescent localisation of tumour necrosis factor-alpha receptors on the
      popliteal lymph node and the surrounding adipose tissue following a simulated
      immune challenge.
AB  - We used immunohistochemical techniques to demonstrate the distribution of
      receptors for the cytokine tumour necrosis factor-alpha on the popliteal lymph
      node and the adipose tissue surrounding it for 5 d following a simulated immune
      challenge to one hind leg in the rat. We found different patterns of expression
      of receptors on adipocytes surrounding a lymph node to a distance of about 1 mm,
      and on those more remote from the node. Sites recognised by an antibody to type I
      tumour necrosis factor receptors appeared on the challenged node and the
      adipocytes surrounding it within 30 min of an injection of bacterial
      lipopolysaccharide, but appeared on adipocytes surrounding the unchallenged
      popliteal node only 24 h later. Adipocytes distant from the node, both within the
      same depot and in the contralateral depot, showed no response. Sites recognised
      by an antibody to type II tumour necrosis factor receptors were present at all
      times on lymph nodes and the adipocytes close to them, but appeared on more
      distant adipocytes only 24 h after immune challenge, in both challenged and
      unchallenged legs. These data support the proposal, based on in vitro studies,
      that the adipose tissue surrounding major lymph nodes is specialised to respond
      to cytokines derived from lymphoid cells, and participates in the immune
      responses of the adjacent node.

PMID- 9643424
TI  - Variation in the apparent density of human mandibular bone with age and dental
      status.
AB  - This study examines the variability in the anatomy of mandibles of differing ages
      and different stages of tooth loss. Mandibles from individuals between 19 and 96
      y were sectioned into 2 mm thick vertical plane-parallel slices and cleaned of
      marrow and periosteum. The apparent density (mass per unit volume in g/ml) from
      midline (MID) and mental foramen region (MF) sites was determined by weighing the
      slices and dividing by a volume calculated as the product of section thickness
      and the mean area of the 2 sides of the section. The cortical thickness of the
      inferior border and the basal and alveolar bone heights were measured in
      radiographs of the slices. Mandibular apparent density was negatively correlated
      with the cross sectional area (midline r=-0.48, mental foramen r=-0.45), and at
      the midline was significantly greater in edentulous than in dentate individuals
      (means (+/-S.E.M.) edentulous n=13: 1.43 (+/-0.07) g/ml; dentate n=17: 1.27 (+/
      0.04) g/ml, P < 0.05). Where a large enough age range was available, mandibular
      apparent bone density showed a significant increase with age (midline males:
      r=0.53, n=18) especially for dentate individuals (r=0.91, n=8). There was a
      correlation between the apparent densities at the two sites in the same mandible
      (r=0.64), with the values obtained for the midline being significantly greater
      than for the mental foramen region (midline 1.34 (+/-0.04) g/ml; mental foramen
      1.19 (+/-0.04) g/ml, P < 0.001, paired t test). The mandible shows great
      interindividual variability, but there may be a considerable reduction in cross
      sectional girth of the mandible following tooth loss, and, unlike postcranial
      sites, an increase in apparent density with age.

PMID- 9643425
TI  - Mineralisation density of human mandibular bone: quantitative backscattered
      electron image analysis.
AB  - This study examined the tissue level mineralisation density distribution in
      mandibles from 88 adult humans. Mandibles (19-96 y) were sectioned vertically in
      midline (MID), mental foramen (MF), and third molar (M3) regions. Surgical
      fragments from M3 were obtained from individuals aged 16-38 y. All specimens were
      cleaned, embedded in PMMA, micromilled and examined by digital 20 kV
      backscattered electron (BSE) stereology. Quantitation was based on rescaling
      image histograms to the signal range between a monobrominated (0) and a
      monoiodinated (255) dimethacrylate resin standard. Mineralisation density
      increased with age (r=0.70; P < 0.0001): the mean for 39 individuals aged between
      16 and 50 y was significantly lower (P < 0.0001) than for 35 individuals over 51
      y (mean (+/-S.E.M.): 158.20 (1.63) and 174.71 (1.27) normalised grey level units
      respectively). There was good correlation in mean mineralisation density between
      different sites in the same mandible, but MID was significantly less highly
      mineralised than the other sites: MID 173.90, MF 177.34, M3 177.11 (P < 0.002 and
      0.01 for MF and M3 respectively; paired t test), as was the alveolar bone density
      when compared with the bone of the inferior cortex (e.g. MID: 171.13 (1.53) and
      174.46 (1.14) P < 0.0001). No sex difference was found. Partially dentate
      mandibles generally had regions of higher mineralisation than fully dentate and
      edentulous mandibles. The lowest density bone occurred at the alveolar crest
      anteriorly and superolingually at M3, matching sites of net resorption following
      tooth loss. Highest densities were found inferolingually at MID, inferiorly at MF
      and buccally at M3, matching the sites thought to experience the highest
      functional strains. This stresses the importance that local factors may have in
      the remodelling of the edentulous mandible. Morphology showed that there is a
      preponderance of highly mineralised cement lines, and of packets containing dead,
      mineralised, osteocytes.

PMID- 9643426
TI  - The organisation of the enteric nervous system in the submucous and mucous layers
      of the small intestine of the pig studied by VIP and neurofilament protein
      immunohistochemistry.
AB  - The arrangement of the enteric ganglia and nerve fibre plexuses was examined in
      the submucous and mucous layers and around Peyer's patches of the porcine small
      intestine to clarify their organisation. Immunohistochemistry of vasoactive
      intestinal peptide (VIP) and neurofilament proteins in wholemounts, chopped or
      paraffin sections was used to locate the neural elements. The ganglia of the
      internal and external submucous plexuses were situated at 2 different topographic
      locations, being clearly demarcated by the submucosal vascular arcades and
      differing in neuronal composition. The internal submucous plexus was the only
      contributor to the plexus surrounding the follicles of Peyer's patches as a
      continuous mesh of 3 ganglionated nerve subplexuses. VIP-immunoreactive fibres
      from this mesh innervated the dome. The mucosal plexus, which was subdivided into
      4 subunits--the outer proprial, inner proprial, pericryptal and villous plexuses-
      contained a few solitary neuronal perikarya. Labelling for neurofilament proteins
      revealed Dogiel types II, IV and VI neurons. The observations reveal several new
      features in the enteric nervous system of the pig and clarify its nomenclature.

PMID- 9643427
TI  - Cartilaginous development of the human craniovertebral junction as visualised by
      a new three-dimensional computer reconstruction technique.
AB  - Serial transverse histological sections of the human craniovertebral junction
      (CVJ) of 4 normal human embryos (aged 45 to 58 d) and of a fetus (77 d) were used
      to create 3-dimensional computer models of the CVJ. The main components modelled
      included the chondrified basioccipital, atlas and axis, notochord, the
      vertebrobasilar complex and the spinal cord. Chondrification of the component
      parts of CVJ had already begun at 45 d (Stage 18). The odontoid process appeared
      to develop from a short eminence of the axis forming a third occipital condyle
      with the caudal end of the basioccipital. The cartilaginous anterior arch of C1
      appeared at 50-53 d (Stages 20-21). Neural arches of C1 and C2 showed gradual
      closure, but there was still a wide posterior spina bifida in the oldest
      reconstructed specimen (77 d fetus). The position of the notochord was constant
      throughout. The normal course of the vertebral arteries was already established
      and the chondrified vertebral foramina showed progressive closure. The findings
      confirm that the odontoid process is not derived solely from the centrum of C1
      and that there is a 'natural basilar invagination' of C2 during normal embryonic
      development. On the basis of the observed shape and developmental pattern of
      structures of the cartilaginous human CVJ, we suggest that certain pathologies
      are likely to originate during the chondrification phase of development.

PMID- 9643428
TI  - Patterns of sexual, bilateral and interpopulational variation in human femoral
      neck-shaft angles.
AB  - Data on femoral neck-shaft angles were collected for 30 modern, historic and
      prehistoric human population samples, and analysed with respect to sexual
      dimorphism, bilateral asymmetry, geographical patterning and general economic
      level. Although some samples had modest sexual dimorphism in this angle, and some
      individuals exhibited clear asymmetry, there were no consistent patterns of
      sexual or side differences across human populations. Similarly, there was no
      evidence for geographic differences, since broad regional groups lacked
      significant differences and mean angles were not correlated with latitude.
      However, there is a significant increase in mean neck-shaft angles across
      populations with an increasingly sedentary existence and with mechanisation. The
      last reflects the developmental plasticity of this feature with respect to
      habitual load levels during ontogeny of the hip region.

PMID- 9643429
TI  - Squatting facets on the neck of the talus and extensions of the trochlear surface
      of the talus in late Byzantine males.
AB  - Remodelling of bone occurs in response to physical stress. Habitual squatting is
      associated with modifications of the neck of the talus (squatting facets) and its
      trochlear/malleolar surfaces (trochlear extensions), and individual populations
      exhibit different incidences of these modifications that reflect their lifestyle.
      The occurrence of talar modifications was therefore investigated in a population
      of late Byzantine (13th century AD) adult male skeletons. Lateral squatting
      facets occurred most frequently (37.7%), but medial (0.6%), combined (0.6%) and
      continuous (gutter-like) facets (0.6%) were also observed. Lateral (8.0%), medial
      (10.9%) and continuous (lateral/central/medial) extensions (4.6%) of the
      trochlear surface were all present in the late Byzantine population. There was no
      evidence of side dimorphism. The occurrence of lateral squatting facets in the
      late Byzantine population was greater than that reported for modern Europeans,
      but similar to that reported for some populations of modern Indians. The
      frequency of occurrence of trochlear extensions in the late Byzantine population
      was substantially less than in modern Indian populations, but similar to modern
      Europeans. Therefore, it is unlikely that precisely the same factors determine
      the expression of squatting facets and trochlear extensions.

PMID- 9643430
TI  - Distribution of lymphoid tissue in the caecal mucosa of chickens.
AB  - In order to clarify the fundamental structure of the host defence mechanism in
      chicken caeca, a detailed analysis of the distribution of lymphoid nodules (LNs)
      was carried out on longitudinal sections of both the mesenteric (side of the
      ileocaecal ligament) and the antimesenteric mucosa. An overwhelming majority of
      solitary or aggregated LNs were located in the mesenteric mucosa, although a few
      were also found in the antimesenteric mucosa. Of the total LNs, 45.7% were
      detected at the proximal 7.8% section in the caecal tonsil. LNs (21.4%) were also
      concentrated in the distal 22.0% section corresponding to the apex. A moderate
      concentration of LNs (13.1%) was found at the transitional 20.0% region between
      the base and body. Approximately 80.2% of total LNs were found at the above 3
      regions in the mesenteric mucosa. In many cases, the frequency of LNs in the
      caecal tonsils was opposite to that at the apices. Aggregated LNs were mainly
      found in the caecal tonsils, transitional region and apex. Almost all aggregated
      LNs consisted of fundamental nodular units possessing M cells in their follicle
      associated epithelia. The aggregated LNs in the above 3 regions therefore could
      provide immunological surveillance against caecal luminal contents. In
      particular, the cooperative function between LNs of the caecal tonsil and apex
      might be highly important in maintaining the caecal microenvironment.

PMID- 9643431
TI  - Postscript on possum cartilage and oxygen; what is keratan sulphate? A
      corrigendum to the addendum.

PMID- 9643432
TI  - Two rare anomalies of the brachial plexus.

PMID- 9643433
TI  - Teaching of gross anatomy to medical undergraduates: general practice as a
      guideline? A synopsis.

PMID- 9643434
TI  - An anomalous muscle in the region of the popliteal fossa: case report.

PMID- 9643435
TI  - Morphology of the articular processes of the sixth cervical vertebra in humans.

PMID- 9643436
TI  - Chitosan-EDTA conjugate: a novel polymer for topical gels.
AB  - A recently developed chitosan-EDTA conjugate, neutralized with sodium hydroxide
      (NaChito-EDTA), has been tested for possible topical use. The technical
      properties and microbial stability of NaChito-EDTA have been compared with those
      of carmellose sodium (NaCMC), hydroxypropylmethylcellulose (HPMC), sodium
      polycarbophil (NaPCP) and sodium carbopol 980 (NaC980), well established
      gelatinizing agents. NaChito-EDTA forms stable, colourless, completely
      transparent hydrogels at a polymer concentration of 0.5%. Of the polymers tested
      the novel polymer had the lowest incompatibility with multivalent cations and
      with ethanol, and much the best swelling properties. After 28 days of incubation
      at room temperature the rates of growth of the complete bacterial spectrum
      occurring in demineralized water and of Escherichia coli, serving as model strain
      representative of gram-negative bacteria, were at least 2 log and 5.7 log,
      respectively, lower in NaChito-EDTA gels than in the other hydrogels. This
      antimicrobial activity of NaChito-EDTA can be explained by its highest binding
      affinity towards magnesium, which stabilizes the outer membrane of gram-negative
      bacteria. However, this antimicrobial effect is insufficient to guarantee
      microbial stability. Further results showed that the antimicrobially acting
      polypeptide nisin can be recommended as an alternative novel preservative for
      NaChito-EDTA gels, because its antimicrobial spectrum could also be increased
      towards gram-negative bacteria in combination with chelating excipients. NaChito
      EDTA seems, therefore, to be a promising novel polymer for topically-used gels,
      with advantages over well established gelatinizing agents.

PMID- 9643437
TI  - Polymeric chitosan-based vesicles for drug delivery.
AB  - A simple carbohydrate polymer glycol chitosan (degree of polymerization 800
      approx.) has been investigated for its ability to form polymeric vesicle drug
      carriers. The attachment of hydrophobic groups to glycol chitosan should yield an
      amphiphilic polymer capable of self-assembly into vesicles. Chitosan is used
      because the membrane-penetration enhancement of chitosan polymers offers the
      possibility of fabricating a drug delivery system suitable for the oral and
      intranasal administration of gut-labile molecules. Glycol chitosan modified by
      attachment of a strategic number of fatty acid pendant groups (11-16 mol%)
      assembles into unilamellar polymeric vesicles in the presence of cholesterol.
      These polymeric vesicles are found to be biocompatible and haemocompatible and
      capable of entrapping water-soluble drugs. By use of an ammonium sulphate
      gradient bleomycin (MW 1400), for example, can be efficiently loaded on to these
      polymeric vesicles to yield a bleomycin-to-polymer ratio of 0.5 units mg(-1).
      Previously polymers were thought to assemble into vesicles only if the polymer
      backbone was separated from the membrane-forming amphiphile by a hydrophilic side
      arm spacer. The hydrophilic spacer was thought to be necessary to decouple the
      random motion of the polymer backbone from the ordered amphiphiles that make up
      the vesicle membrane. However, stable polymeric vesicles for use in drug delivery
      have been prepared from a modified carbohydrate polymer, palmitoyl glycol
      chitosan, without this specific architecture. These polymeric vesicles
      efficiently entrap water-soluble drugs.

PMID- 9643438
TI  - N-acetyl-L-gamma-glutamyl derivatives of p-nitroaniline, sulphamethoxazole and
      sulphamethizole for kidney-specific drug delivery in rats.
AB  - Kidney-specific delivery of p-nitroaniline, sulphamethoxazole and sulphamethizole
      after either intravenous administration of the L-gamma-glutamyl or N-acetyl-L
      gamma-glutamyl derivatives or the parent drugs has been examined in a rat model.
      All L-gamma-glutamyl derivatives were converted to the corresponding parent drugs
      within 60 min whereas the N-acetyl-L-gamma-glutamyl derivatives were fairly
      stable in the systemic circulation after parenteral administration.
      Concentrations of p-nitroaniline and sulphamethoxazole 20 min after
      administration of the parent drugs were somewhat higher in the kidney than in the
      liver and lung. The concentration of sulphamethizole in the kidney was
      dramatically higher than those in the hepatic and pulmonary tissue. Kidney
      specific delivery of the drugs of interest was evaluated by determining the
      tissue concentrations of the released parent drug and the total drug levels (i.e.
      drug levels after hydrolysis of all conjugate to the parent drug). For L-gamma
      glutamyl-p-nitroaniline released renal levels of p-nitroaniline and total p
      nitroaniline concentrations were both higher than those obtained after p
      nitroaniline dosing. Use of L-gamma-glutamylsulphamethoxazole resulted in higher
      total sulphamethoxazole concentrations in the kidney, but did not lead to an
      increase in released (unconjugated) sulphamethoxazole levels. In contrast, no
      kidney-selective distribution was observed for L-gamma-glutamylsulphamethizole.
      Markedly increased kidney distribution was observed for both N-acetyl-L-gamma
      glutamyl-p-nitroaniline and N-acetyl-L-gamma-glutamylsulphamethoxazole and the
      liver and lung concentrations were correspondingly reduced in comparison with
      parent drug dosing. Use of the N-acetyl-L-gamma-glutamyl-p-nitroaniline conjugate
      increased the concentration of p-nitroaniline in the kidney to the same extent as
      did L-gamma-glutamyl-p-nitroaniline. In conclusion, N-acetyl-L-gamma-glutamyl
      derivatization of certain compounds seems to be useful for kidney-specific drug
      delivery and preliminary data suggests that lipophilic drugs are better
      substrates than hydrophilic compounds. Results related to the selectivity of
      tissue distribution of the derivatives and species differences are discussed.

PMID- 9643439
TI  - The effect of a drug-delivery system consisting of soybean phosphatidyl choline
      and medium-chain monoacylglycerol on the intestinal permeability of hexarelin in
      the rat.
AB  - The aim of this study was to investigate if the effective in-situ permeability
      (Peff) of a new growth hormone-releasing peptide, hexarelin, along rat intestine
      was enhanced by a lipid matrix drug-delivery system comprising a mixture of
      soybean phosphatidyl choline and medium-chain monoacylglycerol (PC-MG). The study
      was performed with and without a protease inhibitor, Pefabloc SC. To enable
      better understanding of the mechanism of action of this delivery system we also
      studied the uptake of a small hydrophilic molecule, atenolol. PC-MG at a
      concentration of 15 mmol L(-1) increased the jejunal Peff of hexarelin
      approximately 20-fold, both in the presence and absence of Pefabloc SC, whereas
      Peff was not increased in the ileum and colon. PC-MG had no effect on the
      jejunal, ileal and colonic Peff of atenolol. Complete recovery of the non
      absorbable molecule PEG 4000 showed that functional intestinal viability was
      maintained in all experiments. Although the results obtained in this study are
      promising, pharmacokinetic and toxicological studies are required to investigate
      if this delivery system is a suitable and safe candidate for improving the oral
      bioavailability of hexarelin.

PMID- 9643440
TI  - Novel 5,8-diazabenzo[c]phenanthrenes: synthesis and mutagenicity.
AB  - The polycyclic aromatic hydrocarbons have been recognized as carcinogens and
      mutagens since the early part of this century. More recently their aza and
      polyaza derivatives have been shown to have the same biological activity. A major
      source of these compounds is the combustion of fresh or metamorphosed plant
      materials; this contributes to the environmental burden of, and exposure to,
      these carcinogens. We report the synthesis and characterization of a series of
      novel 5,8-diazabenzo[c]phenanthrenes which are isosteric with the known epidermal
      carcinogen benzo[c]phenanthrene but have not yet been reported as components of
      soot or diesel particulate matter. The synthesis of the compounds exploits a
      versatile, double Friedlander reaction between the appropriately substituted 2,2'
      diaminobenzophenone and beta-diketones, with yields of purified product ranging
      from 30-90%. The nucleophilic substitution of these diazabenzophenanthrenes with
      ethanolamine is also described. This strategy will enable further elaboration of
      these heterocyclic nuclei at a later date. Mutagenicity testing of these agents
      was performed using spot tests and in Ames plate-incorporation assays using
      Escherichia coli WP2 and WP2uvrA as test organisms. The plate-incorporation
      assays were performed in the presence or absence of metabolic enzymes contained
      in the S9 liver fraction from Aroclor 1254-induced rats, to investigate whether
      bioactivation of the diazabenzophenanthrenes contributed to their toxicity. No
      differences between these two protocols were observed, with neither test showing
      reversion to prototrophic behaviour. Furthermore, the compounds were not toxic to
      the test organism. These initial results suggest that these compounds are not
      mutagenic in the Ames tests employed.

PMID- 9643441
TI  - Novel aryl-bis-quinolines with antimalarial activity in-vivo.
AB  - Three rationally designed isomeric aryl-bridged bis-quinolines, N1,Nx-bis(7
      chloroquinolin-4-yl)phenylene-1,x-diamines, where x=2, 3 or 4, i.e. o-, m- and p
      substituted analogues respectively, were synthesized and evaluated against
      Plasmodium berghei in-vivo. The compound with x=2 had an ID50 of 30 mg kg(-1),
      whereas the p-substituted analogue (x=4) was not statistically schizonticidal at
      either of the two dose levels tested in olive oil-dimethylsulphoxide (5 and 25 mg
      kg(-1), ID50=60 mg kg(-1) approx.). When the delivery vehicle was changed to
      saline-DMSO, antimalarial potency increased for the p-substituted compound (ID50
      17 mg kg(-1)). In contrast, the m-substituted analogue had marked antimalarial
      activity (ID50 1.2 mg kg(-1)), which compares favourably with that of chloroquine
      diphosphate (ID50 = 4.3 mg kg(-1)). The data presented show that the
      aminomethylene side chain in amodiaquine can be successfully replaced by a 7-halo
      4-aminoquinoline, establishing that carbon bridges containing less than four
      contiguous carbon atoms can be present within highly active aryl-substituted 4
      aminoquinoline antimalarials. These results confirm that the presence of an OH
      group in the aryl bridge is not necessary for antimalarial activity and
      substantiate the view that, despite the appearance of resistant strains, new and
      existing aminoquinolines still have an important role in treating malaria.

PMID- 9643442
TI  - Interspecies scaling: predicting volumes, mean residence time and elimination
      half-life. Some suggestions.
AB  - Extrapolation of animal data to assess pharmacokinetic parameters in man is an
      important tool in drug development. Clearance, volume of distribution and
      elimination half-life are the three most frequently extrapolated pharmacokinetic
      parameters. Extensive work has been done to improve the predictive performance of
      allometric scaling for clearance. In general there is good correlation between
      body weight and volume, hence volume in man can be predicted with reasonable
      accuracy from animal data. Besides the volume of distribution in the central
      compartment (Vc), two other volume terms, the volume of distribution by area
      (Vbeta) and the volume of distribution at steady state (VdSS), are also
      extrapolated from animals to man. This report compares the predictive performance
      of allometric scaling for Vc, Vbeta and VdSS in man from animal data. The
      relationship between elimination half-life (t(1/2)) and body weight across
      species results in poor correlation, most probably because of the hybrid nature
      of this parameter. To predict half-life in man from animal data, an indirect
      method (CL=VK, where CL=clearance, V is volume and K is elimination rate
      constant) has been proposed. This report proposes another indirect method which
      uses the mean residence time (MRT). After establishing that MRT can be predicted
      across species, it was used to predict half-life using the equation MRT=1.44 x
      t(1/2). The results of the study indicate that Vc is predicted more accurately
      than Vbeta and VdSS in man. It should be emphasized that for first-time dosing in
      man, Vc is a more important pharmacokinetic parameter than Vbeta or VdSS.
      Furthermore, MRT can be predicted reasonably well for man and can be used for
      prediction of half-life.

PMID- 9643443
TI  - Effect of cyclosporin on liver antioxidants and the protective role of vitamin E
      in hyperoxaluria in rats.
AB  - This study aimed to evaluate whether administration of cyclosporin to
      hyperoxaluric rats affects liver antioxidant status, and whether pretreatment
      with vitamin E reverses the effect. Male Wistar rats were divided into two major
      groups of 40. One group was given vitamin E. Both major groups were then divided
      into four subgroups which received vehicle (olive oil), cyclosporin in olive oil
      (50 mg kg(-1)), 3% ammonium oxalate or cyclosporin + 3% ammonium oxalate for
      three days. The activities of liver lactate dehydrogenase, glycolic acid oxidase
      and xanthine oxidase, and the level of malondialdehyde, an indicator of lipid
      peroxidation, increased when cyclosporin was administered to hyperoxaluric rats.
      The levels of antioxidants ascorbic acid, vitamin E and reduced glutathione and
      the activities of glutathione-metabolizing enzymes were altered significantly
      when hyperoxaluric rats were treated with cyclosporin. All these enzymes and
      antioxidants showed highly significant correlation values, r. These changes were
      restored to near normal by pretreatment with vitamin E. These findings suggest
      that cyclosporin-induced hepatotoxicity is aggravated in hyperoxaluria. This was
      almost totally prevented by pretreatment with vitamin E.

PMID- 9643444
TI  - Investigation into the presence of insulin-degrading enzyme in cultured type II
      alveolar cells and the effects of enzyme inhibitors on pulmonary bioavailability
      of insulin in rats.
AB  - The purpose of this study was to investigate the role of insulin-degrading enzyme
      (IDE, EC 3.4.22.11) in insulin degradation in alveolar epithelium. The primary
      culture of isolated rat type-II pneumocytes was used for the in-vitro
      characterization of IDE. Insulin was then administered intratracheally with
      various inhibitors to assess the improvement in its pulmonary bioavailability. In
      cultured type-II pneumocytes, the cytosolic insulin-degrading activity
      contributed 81% of total insulin degradation, reached a maximum at pH 7.5 and had
      an apparent Michaelis-Menten constant (Km) of 135 nM. N-Ethylmaleimide, p
      chloromercuribenzoic acid and 1,10-phenanthroline inhibited insulin-degrading
      activity almost completely in both crude homogenate and cytosol. An
      immunoprecipitation study showed that IDE contributed 74% of cytosolic insulin
      degrading activity. Western blot analysis showing a single band of 110 kDa on
      reduced SDS (sodium dodecylsulphate) gels confirmed the presence of IDE in
      cultured type-II cells. When given intratracheally with insulin, inhibitors
      including N-ethylmaleimide, p-chloromercuribenzoic acid, and 1,10-phenanthroline
      significantly enhanced the absolute bioavailability of insulin and the compound's
      hypoglycaemic effects. These results suggest that IDE is present in alveolar
      epithelium and might be involved in limiting insulin absorption in the lung.

PMID- 9643445
TI  - Metabolism of roxithromycin in the isolated perfused rat liver.
AB  - Roxithromycin is a macrolide antibiotic with high clinical potency. N
      Demethylation is considered to be one of the main pathways of roxithromycin
      metabolism in rats. We have studied the hepatic metabolism of roxithromycin in
      the isolated perfused rat liver. After addition of roxithromycin (30 microM) to
      the perfusion medium the parent compound and one major metabolite were detected
      in bile by high-performance liquid chromatography. The metabolite was identified
      as monodesmethylated roxithromycin by mass spectrometric analysis. Onset of
      biliary excretion of native roxithromycin was fast, reaching a maximum (130.52 +/
      43.88 pmol g(-1) min(-1)) after only 10 min, whereas excretion of the metabolite
      was delayed (maximum 75.83 +/- 11.92 pmol g(-1) min(-1) at 30 min). The
      cumulative excretion of roxithromycin and its metabolite into bile during the 60
      min of application amounted to only 1.09 +/- 0.30 and 0.64 +/- 0.22% of the
      roxithromycin cleared from the perfusate during the same time. The liver content
      was 0.48 micromol (g liver)(-1), indicating high retention within the organ. No
      release of the metabolite into the perfusate was detected. In conclusion, this
      study has demonstrated the importance of phase-I metabolism for the biliary
      excretion of roxithromycin in rat liver. These findings might be predictive of
      roxithromycin biotransformation and biliary excretion in man.

PMID- 9643446
TI  - Biochemical and pharmacological characteristics of 3-butyryl-8-methoxy-4-[(2
      thiophenyl)amino]quinoline, a new proton-pump inhibitor, in rabbit gastric
      microsomes and in rats.
AB  - We have investigated the properties of the newly synthesized proton-pump
      inhibitor, 3-butyryl-8-methoxy-4-[(2-thiophenyl)amino]quinoline (YJA20379-6), on
      gastric mucosal proton-pump (H+/K+-ATPase) activity, gastric acid secretion and
      gastroduodenal lesions in experimental rats. YJA20379-6 markedly inhibited H+/K+
      ATPase activity in rabbit isolated gastric mucosal microsomes, confirming its
      classification as a proton-pump inhibitor. The inhibitory efficacy of YJA20379-6
      on the proton pump was approximately 14-times higher than that of omeprazole at
      pH 7.4. YJA20379-6 given intraduodenally had a potent inhibitory effect on
      gastric secretion in pylorus-ligated rats (ED50 22.9 mg kg(-1)) but was less
      active than omeprazole. Pretreatment of rats with YJA20379-6 dose-dependently
      protected the gastric mucosa from damage induced by water-immersion stress,
      indomethacin and absolute ethanol, and the duodenal mucosa from damage induced by
      mepirizole. Repeated administration of YJA20379-6 also dose-dependently
      accelerated the spontaneous healing of acetic acid-induced gastric ulcers. These
      results suggest that YJA20379-6 has potent anti-secretory and anti-ulcer effects
      which are exerted by suppression of H+/K+-ATPase activity in gastric parietal
      cells. YJA20379-6 might be useful for the clinical treatment of peptic ulcer
      diseases.

PMID- 9643447
TI  - Effects of 17beta-oestradiol on rat isolated coronary and mesenteric artery tone:
      involvement of nitric oxide.
AB  - Pre- and post-menopausal women receiving oestrogen replacement therapy have a
      significantly reduced risk of cardiovascular disorders. It has been suggested
      that this protection might be partly a result of a direct relaxant effect of
      oestrogens on coronary arteries. This study examines and directly compares the
      effects of 17beta-oestradiol on rat isolated coronary and mesenteric vessels. The
      influence of nitric oxide on these responses was also investigated. 17Beta
      oestradiol caused similar concentration-dependent relaxation of isolated coronary
      and mesenteric resistance arteries pre-contracted with either KCl (60 mM) or 9,11
      dideoxy-11alpha,9alpha-epoxymethanoprostaglandin (U46619; 1 microM). The
      relaxation responses to 17beta-oestradiol were significantly reduced, but not
      totally inhibited, in the presence of N(omega)-nitro-L-arginine methyl ester (L
      NAME), an inhibitor of nitric oxide synthase; they were not altered by
      indomethacin, an inhibitor of prostaglandin synthesis. The responses to 17beta
      oestradiol in the presence of L-NAME were not dependent on the vessel studied or
      the pre-contracting agent used. These results suggest that nitric oxide might
      contribute to the vasodilatory effects of 17beta-oestradiol in rat isolated
      coronary and mesenteric resistance arteries.

PMID- 9643448
TI  - 5-Hydroxytryptamine-induced secretion by rat jejunum in-vitro involves several 5
      hydroxytryptamine receptor subtypes.
AB  - The receptors contributing to 5-hydroxytryptamine (5-HT)-induced anion secretion
      by rat jejunum have been investigated by testing the effects of selective
      agonists and antagonists in-vitro using both intact and stripped intestinal
      sheets. In both intact and stripped jejunum 5-HT and 5-methoxytryptamine, an
      agonist that lacks affinity for 5-HT3 receptors, induced concentration-dependent
      increases in the short-circuit current (SCC), although 5-methoxytryptamine
      induced a smaller maximum response. In intact sheets 1-phenylbiguanide, a
      selective 5-HT3 agonist, induced a response that was similar in magnitude to that
      of 5-methoxytryptamine, but in stripped preparations it had little effect.
      Tetrodotoxin inhibited the response of intact jejunum to 5-HT (by 86%) and 5
      methoxytryptamine (by 85%) and abolished the response to 1-phenylbiguanide. In
      stripped sheets inhibition of the 5-HT response by tetrodotoxin was reduced to
      27%. Desensitization to 1-phenylbiguanide reduced the response to 5-HT in intact
      but not stripped sheets whereas, in contrast, desensitization to 5
      methoxytryptamine inhibited the 5-HT response in stripped sheets but was without
      effect in intact sheets. Mianserin, a 5-HT1, 5-HT2 and 5-HT3 antagonist, and
      renzapride, a 5-HT1 and 5-HT3 antagonist, both reduced the maximum response to 5
      HT, but 5-HTP-DP, a 5-HT1 antagonist, was without effect. The 5-HT3 antagonist
      granisetron reduced the response to 5-HT in intact, but not in stripped sheets.
      Tropisetron, a 5-HT3 and 5-HT4 antagonist, inhibited the response to 5
      methoxytryptamine in both preparations, but did not alter the response to 5-HT.
      It is concluded that 5-HT-induced jejunal secretion involves more than one 5-HT
      receptor subtype, with both neural and non-neural mechanisms contributing to the
      response.

PMID- 9643449
TI  - Effect of D-002 on the pre-ulcerative phase of carrageenan-induced colonic
      ulceration in the guinea-pig.
AB  - D-002 is a natural mixture of higher aliphatic primary alcohols, isolated and
      purified from beeswax which has anti-inflammatory properties, reduces
      leukotrienes (LTB4) and thromboxane B2 (TXB2) in exudated carrageenan-induced
      pleurisy, and has anti-ulcer activity in different experimental models. This
      study was conducted to determine the effect of D-002 on the pre-ulcerative phase
      of carrageenan-induced colonic ulceration in guinea-pigs. Animals were randomly
      distributed among a negative control, a positive control group treated with the
      vehicle Tween 20 in H2O and two experimental groups receiving D-002 at 25 and 50
      mg kg(-1). All treated animals received degraded carrageenan for three days for
      induction of colonic ulceration. Significant reductions in wet weight, wall
      thickness, counts of infiltrating polymorphonuclear neutrophils and of
      macrophages, and histological index were observed in colonic mucosa of D-002
      treated animals compared with controls. It is concluded that D-002 has a
      protective effect on the pre-ulcerative phase of carrageenan-induced colonic
      ulceration in the guinea-pig.

PMID- 9643450
TI  - Effects of the ginsenosides Rg1 and Rb1 on morphine-induced hyperactivity and
      reinforcement in mice.
AB  - Recent studies have demonstrated that ginseng saponin inhibits the hyperactivity
      and conditioned place-preference response induced by psychostimulants and
      opiates. This seems to occur by direct or indirect modulation of dopaminergic
      activity. However, it is not known which components of ginseng saponin are
      active. These experiments were conducted to determine the effects of the
      ginsenosides Rb1 and Rg1, major components of the protopanaxadiol and
      protopanaxatriol fractions of ginseng saponin, on morphine-induced hyperactivity
      and conditioned place-preference. Morphine-induced hyperactivity, but not
      apomorphine-induced climbing behaviour, was inhibited by both Rb1 and Rg1. These
      findings confirm the hypothesis that ginsenosides modulate catecholaminergic
      activity preferentially at pre-synaptic sites. Morphine-induced conditioned place
      preference was inhibited by Rg1, but not by Rb1. It has previously been shown
      that at low doses Rb1 and Rg1 are equally effective at inhibition of
      catecholamine secretion at the pre-synaptic site, but that at high doses Rg1 is a
      more effective inhibitor. This observation might explain our finding that
      morphine-induced conditioned place-preference was inhibited by Rg1 only. Our
      findings suggest that Rg1, a component of ginseng saponin with appropriate
      activity, might be a useful agent for prevention and treatment of the adverse
      effects of morphine.

PMID- 9643451
TI  - Flavonoids reduce morphine withdrawal in-vitro.
AB  - The effects of quercetin, flavone, catechin and chrysin on the naloxone
      precipitated withdrawal contracture of the acute morphine-dependent guinea-pig
      ileum have been investigated in-vitro. After 4 min in-vitro exposure to morphine
      a strong contracture of guinea-pig isolated ileum was observed after the addition
      of naloxone. All the flavonoids, injected 10 min before morphine at
      concentrations between 10(-7) and 10(-5) M, were capable of blocking naloxone
      induced contracture after exposure to morphine in a concentration-dependent
      fashion. IC50 values calculated for quercetin, flavone, catechin and chrysin were
      2.7 x 10(-6), 7.3 x 10(-7), 8.5 x 10(-7) and 5.3 x 10(-6) M, respectively. These
      results suggest that flavonoids might play an important role in the control of
      morphine withdrawal.

PMID- 9643452
TI  - Plasma salicylate levels in surgical patients during the postoperative period.

PMID- 9643453
TI  - Analysis of the phenotype and phagocytic activity of monocytes/macrophages from
      cattle infected with the bovine leukaemia virus.
AB  - The bovine leukaemia virus (BLV) is a retrovirus that infects mainly B
      lymphocytes of cattle, but proviral DNA can also be isolated from
      monocytes/macrophages. This study investigated the effect of BLV infection on
      surface antigens on freshly isolated peripheral blood monocytes and cultured
      monocyte-derived macrophages, with and without lipopolysaccharide (LPS)
      stimulation. The effect of BLV infection on phagocytic activity of CD14+
      monocytes was also assessed. The percentage of monocytes expressing the surface
      antigens CD11b, CD32 (FcgammaRII), MHC class II and the surface antigen
      recognised by mAb DH59B were increased in BLV-positive cattle. In contrast,
      expression intensity of all markers was low in samples from BLV-positive cattle.
      CD14+ monocytes from BLV-positive cattle showed less Fcgamma-receptor-mediated
      phagocytosis compared to monocytes from BLV-negative cattle. After 7 days in
      culture, there was evidence for shedding/downregulation of surface antigens on
      monocyte-derived macrophages, in particular on cells from BLV-positive cattle.
      LPS stimulation decreased the percentage of cells expressing the measured markers
      in monocyte-derived macrophages taken from BLV-negative cattle, but not in
      cultures derived from BLV-positive cattle. The results provide further evidence
      for an altered function of monocytes and macrophages in BLV-infected cattle.

PMID- 9643454
TI  - Enzymatic amplification and expression of bovine interleukin-1 receptor
      antagonist cDNA.
AB  - cDNA generated from lipopolysaccharide-stimulated bovine peripheral blood
      mononuclear cells was used to amplify and clone the bovine interleukin-1 receptor
      antagonist (IL-1ra) using primers derived from semi-conserved regions between
      human and mouse IL-1ra sequences. 5' and 3' terminal sequences of bovine IL-1ra
      were amplified by 5' and 3' rapid amplification of cDNA ends. The deduced amino
      acid sequence of bovine IL-1ra demonstrated 80%, 78%, 78%, 77% and 76% homology
      with human, mouse, rat, rabbit and equine sequences, respectively. Recombinant
      bovine IL-1ra produced in Escherichia coli suppressed the growth inhibitory
      activity of bovine IL-1beta on A375 cells in a dose-dependent manner, indicating
      that the present bovine IL-1ra cDNA encodes biologically active proteins.

PMID- 9643455
TI  - Characterization of differentially expressed genes in the bovine T lymphoma cell
      line.
AB  - A differential display (D.D.) analysis was made to detect differentially
      expressed genes in a bovine T lymphoma cell line, BTL-26, derived from the calf
      type of sporadic bovine lymphosarcoma. A D.D. analysis comparing BTL-26 with the
      bovine epithelial cell line CKT-1 and healthy bovine thymocytes yielded 24 cDNA
      clones. The DNA sequencing analysis followed by a homology search showed that 20
      of the 24 cDNA clones had no significant homology to any sequences in DNA data
      base. The remaining four genes were homologous to known sequences. Northern blot
      hybridization among BTL-26, CKT-1 and healthy bovine thymocytes showed that a
      cDNA clone, BC8, was differentially expressed in BTL-26. The cloning of full
      length cDNA for the BC8 clone and its DNA sequences showed that the BC8 clone is
      a bovine nuclear domain protein homologous to the human NDP52 gene. Northern blot
      analysis showed that the BC8 clone bovine NDP52 was predominantly expressed in
      tumor cell line BTL-26, compared with the transcripts from several bovine
      tissues.

PMID- 9643456
TI  - The effects of virus-specific antibodies on the replication of bovine respiratory
      syncytial virus in vitro and on clinical disease and immune responses in lambs.
AB  - Low concentrations of antibodies, specific to human respiratory syncytial virus
      (RSV) have been shown to enhance virus replication in human monocytic cell lines
      by several workers. In the present study, replication of bovine RSV in ovine
      peripheral blood monocytes was shown to be enhanced in the presence of low
      concentration of bovine RSV-specific antibodies. Antibodies had no enhancing
      effect on virus replication in secondary lamb testis cells or monocytic cell
      lines derived from peripheral blood monocytes. The possible effects of low titres
      of bovine RSV-specific antibodies on the development of clinical disease were
      examined by inoculating groups of lambs with a mixture of virus and antibodies
      and assessing the severity of clinical disease and by measuring venous oxygen
      (PO2) and carbon dioxide (PCO2) tensions, as hypoxia has been associated with
      respiratory diseases. Inoculation of bovine RSV and virus-specific antibody
      complexes to lambs did not enhance clinical disease and had no effect on the
      clinical chemistry, haematology and PO2 and PCO2 tensions. Groups of lambs
      inoculated with virus alone or virus-antibody complexes developed significant
      humoral and cellular immune responses. There was no significant difference in the
      cellular immune responses of lambs exposed to virus alone and lambs exposed to
      virus-antibody mixture, as measured by virus-specific lymphocyte transformation
      or by cytotoxicity assays but the period of virus shedding was longer in lambs
      inoculated with a mixture of virus and immune serum.

PMID- 9643457
TI  - Flow cytometric measurement of neutrophil alkaline phosphatase before and during
      initiation of an induced Escherichia coli mastitis in cattle.
AB  - In 12 healthy cows, neutrophil alkaline phosphatase (NAP) activity was measured
      by flow cytometer before and during an experimentally induced Escherichia coli
      mastitis, to study the role and increase of NAP in Gram-negative bacterial
      infections. Percentage of neutrophils containing alkaline phosphatase and
      intensity of NAP activity were measured. Preinfection percentage of neutrophils
      with enzyme activity varied between 64.0% and 84.4% and the intensity of enzyme
      activity was low in all cows. After induction of infection, percentage of
      neutrophils with enzyme activity showed a significant decrease on day 1 followed
      by an significant increase on day 3. NAP intensity increased significantly on the
      second and third day after infection. This increase of intensity was
      significantly, positively correlated with the severity of infection. From this
      study we may conclude that variation in susceptibility to E. coli mastitis could
      not be explained by preinfection NAP levels. The post-infection increase of NAP
      activity, that was found following an induced infection was more a result of
      increased enzyme intensity per neutrophil, then from an increase of percentage
      neutrophils with enzyme activity. Furthermore, a strong correlation was found
      between NAP intensity and severity of inflammation. There was evidence that the
      more severely diseased animals showed stronger NAP intensity increase.

PMID- 9643458
TI  - Zinc, thymic endocrine activity and mitogen responsiveness (PHA) in piglets
      exposed to maternal aflatoxicosis B1 and G1.
AB  - Growth retardation, thymic involution and impaired peripheral immune efficiency
      are constant events in piglets exposed to maternal aflatoxicosis. Zinc may play a
      key role because of its requirement for good immune responses, including thymic
      endocrine activity. Zinc is required to activate a thymic hormone, i.e. thymulin
      (ZnFTS), which is responsible for cell-mediated immunity. Zinc deficiency and
      decreased thymic endocrine activity are present in piglets fed from sows exposed
      to aflatoxins (AF) B1 and G1 as compared with healthy control piglets. In
      particular, active ZnFTS is decreased while concentrations of inactive thymulin
      (FTS) are high. The in vitro addition of zinc up to the plasma samples induces a
      reduction of inactive thymulin. The lymphocytes mitogen responsiveness (PHA) is
      decreased and a thymic cortical lymphocyte depletion is also present. These data
      suggest that the thymic defect, followed by impaired peripheral immune
      efficiency, may largely depend by the low peripheral zinc bioavailability to
      saturate all thymulin molecules produced.

PMID- 9643459
TI  - Induction of a local and systemic immune response using cholera toxin as vehicle
      to deliver antigen in the lamina propria of the chicken intestine.
AB  - In this study, the humoral mucosal immune response to a recombinant Eimeria
      antigen (Ea1A) was enhanced using cholera toxin (CT). Chickens were primed intra
      intestinally with Ea1A either conjugated or not to CT. The local and systemic
      antibody responses to both Ea1A and CT were determined to find out whether the
      chickens could respond to CT and whether both antigens had reached the lamina
      propria. In addition the effects of CT on lamina propria leukocytes were
      examined. The results showed that chickens had receptors on the caecal epithelium
      that could bind CT. At day 7 after administration, the number of CD4+ and CD8+ T
      lymphocytes in the lamina propria of the caecum had increased, indicating that CT
      had a specific immunological effect. At this timepoint, anti-CT antibody
      containing cells were detected locally in the lamina propria of the caecum. In
      serum all antigen preparations containing CT induced IgM and IgG antibody titres
      specific for CT within 10 days after priming. In addition, the recombinant Ea1A
      antigen also induced serum responses when administered together with CT or
      conjugated to CT, thus both CT and the antigen had reached the lamina propria.
      Nevertheless, the Ea1A specific response was much higher in the primary response
      and after booster immunization when the antigen was conjugated to CT than when
      only mixed with CT. Therefore, we conclude that CT is a suitable adjuvant for
      intra-intestinal application in chickens, especially when the antigen is
      conjugated to it.

PMID- 9643460
TI  - Expression of surface antigens on blood and mammary leukocytes in lactating and
      dry ewes.
AB  - Flow cytometry was used to study the expression of CD4, CD8, CD14, CD18, WC1,
      MHCII, B-cell and L-selectin on CD45+ leukocytes in ovine blood and mammary
      secretions from lactating and dry ewes. The proportion of CD4+ lymphocytes was
      significantly lower and the proportion of CD8+ lymphocytes significantly higher
      in mammary secretions than in blood. This suggests that a selective migration to
      or retention of CD8+ cells in favour of CD4+ cells occurs in the mammary gland. L
      selectin staining intensity on lymphocytes and neutrophils was lower in mammary
      secretions than in blood. In contrast, CD18 staining intensity was higher on
      leukocytes in milk, but not in dry secretions, than on corresponding cells in
      blood. These changes in adhesion molecules are in accord with shedding of L
      selectin and up-regulation of CD18 during transendothelial migration. Expression
      of leukocyte antigens differed with lactational status mainly in mammary
      secretions. In milk, the staining intensity of CD18+ lymphocytes and neutrophils
      was higher than in dry secretions and more milk neutrophils expressed L-selectin.
      In contrast, greater numbers of IL-2R+ and MHCII+ lymphocytes and CD14+
      leukocytes were observed in dry secretions. An increased proportion of these
      subpopulations could lead to increased immunological responsiveness of the udder
      during the dry period.

PMID- 9643461
TI  - HIV, AIDS, and other health risks: findings from a multisite study--an
      introduction.
AB  - In late 1990 the National Institute on Drug Abuse (NIDA) initiated the
      Cooperative Agreement (CA) for AIDS Community-Based Outreach/Intervention
      Research Program. The goal of this program was to prevent the further spread of
      HIV among out-of-treatment drug users, in particular injection drug users (IDUs)
      and crack cocaine users, their sexual partners, and those at risk for initiating
      injection behavior. To accomplish this goal, the CA set out to monitor drug use
      and HIV risk behaviors, assess the efficacy of various HIV risk reduction
      interventions, and develop and refine outreach and intervention strategies.
      Twenty-three research sites, 21 rural and urban sites in the United States and
      one each in Puerto Rico and Brazil, were included in the CA program. This article
      presents an overview of the CA as well as a synopsis of the studies covered in
      this special issue examining the total CA database.

PMID- 9643462
TI  - A cluster analysis of not-in-treatment drug users at risk for HIV infection.
AB  - The purpose of the analysis described here was to classify not-in-treatment drug
      users participating in the National Institute on Drug Abuse (NIDA)-sponsored
      Cooperative Agreement study into several "homogeneous" HIV risk groups using
      cluster analysis. Data for this analysis (N=17,778) were collected at 19 study
      sites in the United States and Puerto Rico. Measures selected for the cluster
      analysis were limited to (a) current drug use and HIV risk behaviors, (b)
      mutually exclusive behaviors, (c) behaviors directly related to HIV risk, and (d)
      behaviors that were not statistically rare. Eight homogeneous HIV risk clusters
      were produced. Crack cocaine use was the most distinguishing feature of three
      clusters. Another three clusters were distinguishable by drug injection and
      needle use practices. Two additional clusters could not be grouped with either
      the crack- or the injection-dominant clusters. Prostitution was the most
      distinguishing risk behavior of one of these clusters, and extremely high drug
      injection frequencies and relative rates of risky needle use characterized the
      other. Composition of the clusters varied significantly by gender,
      race/ethnicity, educational attainment, and drug use characteristics. In
      addition, perceptions and behaviors initiated to reduce the chances of becoming
      infected with HIV varied by cluster. Subjects in the crack-predominant clusters
      reported low perceptions of the chances of getting AIDS. Perceptions of the
      chances of becoming infected with HIV among subjects in the injection-predominant
      clusters were strongly related to injection frequency. Seroprevalence was also
      related to cluster. Higher rates of HIV infection were evident among the
      injection-predominant clusters, and higher rates were related to frequency of
      injection and the rate of risky needle use. Among the crack-predominant clusters,
      the relationship between drug use and sexual behaviors and HIV infection was less
      clear.

PMID- 9643463
TI  - Needle transfer among injection drug users: a multilevel analysis.
AB  - OBJECTIVE: The purpose of the study described here is to extend our understanding
      of needle transfer behaviors among injection drug users (IDUs) by combining both
      micro and macro variables in a multilevel model. METHODS: A sample of 8,404 IDUs
      interviewed at 18 sites of the National Institute on Drug Abuse (NIDA)
      Cooperative Agreement for AIDS Community-Based Outreach/Intervention Program
      (COOP) was used for the study. A multilevel model was employed to deal with
      intraclass correlation in the sample and to evaluate the impact of micro and
      macro variables on needle transfer among IDUs. RESULTS: A significant intraclass
      correlation was detected in the sample. Needle transfer was associated with both
      the individual characteristics and the features of the social setting in which
      they were embedded. Some of the micro slopes were fixed, while some varied from
      site to site, depending on the values of macro variables. The micro intercept and
      the micro slope of ethnicity vary randomly across social settings, while they are
      partially determined by macro variables. CONCLUSION: Considering the intraclass
      correlation in the data and the effects of contextual features on individual
      behaviors, multilevel analysis of HIV risk behaviors should be considered when
      combining data from micro and macro levels (e.g., individual and project site
      levels).

PMID- 9643464
TI  - Cluster analysis of HIV intervention outcomes among substance-abusing women.
AB  - The study described here presents an innovative approach to analyzing
      intervention outcomes among women substance abusers participating in a national
      HIV prevention research study funded by the National Institute on Drug Abuse. We
      used cluster analysis to divide the women in our sample (N=557) into four
      distinct subgroups predominantly characterized by differences in drug use,
      injecting risk, sexual behaviors, and drug and sexual risk combined. The four
      subgroups resulting from this process were primary crack-using women, primary
      needle-using women, high-frequency needle-using women, and women with multiple
      drug and sex risk behaviors. Our analysis focuses on changes in self-reported
      risk behaviors from baseline to 6-month follow-up. In general, the results
      clearly indicate that the women are heterogeneous; that is, the subgroups exhibit
      varying patterns of drug use, injecting risk, sexual behavior, and HIV
      seropositivity. Significant outcomes were found in many areas, indicating
      positive changes in risk behaviors. The two smaller subgroups of women--high
      frequency needle users and those in the multiple-risk behavior subgroup--reported
      the highest rate of high-risk behaviors and seropositivity but also showed the
      greatest change at follow-up. A particularly important finding resulting from our
      analytical approach is that well over half the women in our sample were primary
      crack users (n=313). This finding is even more significant in light of the fact
      that the Cooperative Agreement specifically tried to include 70% or more
      participants who were injectors. Although the rate of HIV seropositivity is not
      as high for this crack-using subgroup as for the two smaller needle-using
      subgroups, a greater number of "women who are HIV positive" are in this primary
      crack-using subgroup than in all the other subgroups. Most of the crack-using
      women reported that they were not currently injecting drugs and never shared
      needles, but 10% were seropositive for HIV, suggesting that their risk comes
      primarily from sexual behaviors. Behaviors in this larger subgroup of women did
      not change as dramatically as those of women in the smaller subgroups; however,
      the women did show improvement in areas related to indirect risk (e.g., alcohol
      and crack use) and in several areas where change is most needed (e.g., trading
      sex for drugs and using condoms). The results demonstrate a promising alternative
      approach to analyzing substance abuse and HIV risk behaviors, and they suggest
      the need for further research on alternative interventions for women with
      different patterns of risk behaviors.

PMID- 9643465
TI  - The effect of entering drug treatment on involvement in HIV-related risk
      behaviors.
AB  - The research described here is based on a sample of 8,241 out-of-drug-treatment
      users of injected drugs and/or crack, aged 18 or older, recruited from 22 sites
      across the United States and Puerto Rico. The study divided respondents into
      three groups-(a) cocaine or crack users who did not also use heroin or speedball
      (cocaine-only users), (b) heroin injectors who did not also use cocaine or crack
      or speedball (heroin injectors), and (c) users of cocaine or crack and injected
      heroin or speedball (dual users)--and compared the efficacy of entering drug
      treatment for these groups' involvement in HIV-related risk behaviors. The study
      found that entry into treatment corresponded to greater reductions in substance
      abusers' frequency of drug use and involvement in risky injection practices
      compared to those observed in people who did not enter treatment between their
      baseline and 6-month follow-up interviews. Entry into drug treatment was also
      associated with reductions in the practice of risky sexual behaviors, but these
      reductions were less substantial and less consistent than those noted for drug
      use and injection risk behaviors.

PMID- 9643466
TI  - Gonorrhea among drug users: an Alaskan versus a national sample.
AB  - The study described here investigates the replicability of gender-specific risk
      profiles for gonorrhea based on an Alaskan sample compared to a U.S. national
      sample of drug users at risk for HIV infection. The Alaska sample (interviewed at
      a field station in Anchorage, Alaska; N=1,049) and the national sample
      (interviewed at 18 sites other than Alaska; N=17,619) consisted of cocaine
      smokers and injection drug users not in drug treatment. A history of gonorrhea
      infection was self-reported and coded as ever or never. The Anchorage and
      national risk profile for men included the following factors: (a) history of
      intranasal or parenteral cocaine use, (b) being black versus nonblack, (c) being
      older, (d) income from illegal activity, and (e) history of amphetamine use. The
      Anchorage and national risk profiles for women included the following factors:
      (a) trading sex for money, (b) being Native American versus non-Native American,
      and (c) trading sex for drugs. The Anchorage model for women included perceived
      homelessness as a factor, but it was not retained in the national model. The
      extent of the replicability of these models illustrates the generalizability of
      Alaskan findings to other U.S. drug-using populations. The authors also discuss
      the implications of these findings for disease prevention.

PMID- 9643467
TI  - Prevalence of HIV infection and HIV risk behaviors associated with living place:
      on-the-street homeless drug users as a special target population for public
      health intervention.
AB  - The study described here examined the prevalence of HIV infection as a function
      of place of residence and high-risk behaviors in six subpopulations of out-of
      treatment drug injectors and crack cocaine users who participated in the National
      Institute on Drug Abuse (NIDA) Cooperative Agreement project. The subpopulations
      were blacks, Hispanics, and non-Hispanic whites sampled separately by gender. The
      research asked three questions: (a) Is the HIV infection rate higher among the on
      the-street homeless than among those in other places of residence? (b) Do high
      risk drug-related behaviors differ by housing status? and (c) What are the joint
      effects of high-risk drug-related behaviors and housing status on the probability
      of HIV infection? Overall, on-the-street homeless had a significantly higher HIV+
      rate (19.0%) than the study population as a whole (11.2%). Rates differed by
      gender and race, with exceptionally high HIV+ rates for on-the-street homeless
      Hispanic males (29%) and females (32%) and for on-the-street homeless black
      females (38%). Having used drug works previously used by a HIV-infected person
      was a strong predictor of HIV+ status, as was frequency of drug injections and
      crack use. Having multiple sex partners was also a significant risk behavior.
      Findings argue against considering on-the-street homelessness as equivalent to
      shelter dwelling or aggregated homelessness for purposes of the AIDS epidemic. On
      the-street homeless drug users were at strong risk for acquisition and
      transmission of HIV infection and therefore in need of targeted-racially
      relevant, ethnically relevant, and gender-relevant-public health interventions to
      help prevent the spread of AIDS.

PMID- 9643468
TI  - Variation in drug injection frequency among out-of-treatment drug users in a
      national sample.
AB  - This article analyzes data on drug injection frequency in a sample of more than
      13,000 out-of-treatment drug injectors interviewed across 21 U.S. cities and
      Puerto Rico through the National Institute on Drug Abuse (NIDA) Cooperative
      Agreement for AIDS Community-Based Outreach/Intervention Research Program. The
      goals of the article are to present findings on injection frequency and to
      predict variation in terms of a set of variables suggested by previous research,
      including location, ethnicity, gender, age, educational attainment, years since
      first use of alcohol and marijuana, income, living arrangement, homelessness,
      drugs injected, and duration of injection across drugs. Three models were tested.
      Significant intersite differences were identified in injection frequency,
      although most of the other predictor variables we tested accounted for little of
      the variance. Ethnicity and drugs injected, however, were found to be
      significant. Taken together, location, ethnicity, and type of drug injected
      provide a configuration that differentiated and (for the variables available for
      the analysis) best predicted injection frequency. The public health implications
      of these findings are presented.

PMID- 9643469
TI  - ELISA for the detection of venom antigens in experimental and clinical envenoming
      by Loxosceles intermedia spiders.
AB  - Enzyme linked immunosorbent assays (ELISA) were developed to detect antigens from
      Loxosceles intermedia spider venom. Hyperimmune horse anti-Loxosceles intermedia
      IgGs were prepared by immunoaffinity chromatography and used to set up a sandwich
      type ELISA. The specificity of the assay was demonstrated by its capacity to
      correctly discriminate the circulating antigens in mice that were experimentally
      inoculated with L. intermedia venom from those inoculated with L. gaucho, L.
      laeta, and Phoneutria nigriventer spider venoms, Tityus serrulatus scorpion venom
      and Bothrops jararaca, Crotalus durissus terrificus, Lachesis muta muta and
      Micrurus frontalis snake venoms. Measurable absorbance signals were obtained with
      0.8 ng of venom per assay. The ELISA also detected antigens in the sera of
      patients envenomed by L. intermedia. Therefore, after standardization for
      clinical use this ELISA may be a valuable tool for clinicians and
      epidemiologists.

PMID- 9643470
TI  - Recovery from the lethal effects of saxitoxin: a therapeutic window for 4
      aminopyridine (4-AP).
AB  - We have shown that saxitoxin (STX) induced lethality can be reversed by 4-AP when
      it is administered at the time of respiratory arrest [Benton, B. J., Spriggs, D.
      L., Capacio, B. R. and Chang, F.-C. T. (1995) 4-Aminopyridine antagonizes the
      lethal effects of saxitoxin (STX) and tetrodotoxin (TTX). International Society
      of Toxicology, 5th Pan American Symposium on Animal, Plant and Microbial Toxins,
      Frederick, MD. July/August 1995, p. 217]. The purpose of this study was to
      determine whether 4-AP's efficacy could be enhanced further when administered at
      different times relative to STX intoxication. The animals used in this study were
      chronically instrumented for concurrent recordings of diaphragm electromyogram
      (DEMG), neck skeletal muscle electromyogram, Lead II electrocardiogram, and
      electrocorticogram (ECoG). There were five groups of unanesthetized guinea pigs.
      The first group served as 4-AP controls and received a 2 mg/kg i.m. dose of 4-AP.
      The four remaining groups were given a lethal dose of STX (5 microg/kg i.m.); the
      second group, STX controls, received no 4-AP; the third group, the 4-AP treatment
      group, received 4-AP immediately following cardiorespiratory collapse; the fourth
      group was the 4-AP/STX co-administration group and 4-AP was given concurrently
      with STX; and the fifth group was the 4-AP pretreatment group in which 4-AP was
      given 10 min before STX. At the point of STX-induced cardiorespiratory collapse,
      the guinea pigs were ventilated and given an i.p. injection of sodium
      bicarbonate. Results showed that 4-AP prevented cardiorespiratory collapse in 3/7
      animals in the 4-AP pretreatment group. Also, 4-AP in conjunction with artificial
      ventilation and sodium bicarbonate accelerated recovery from STX-induced
      cardiorespiratory collapse in all the treatment groups compared to the STX
      controls.

PMID- 9643471
TI  - Purification and properties of phospholipases A2 from the crown-of-thorns
      starfish (Acanthaster planci) venom.
AB  - Two phospholipases A < inf2 (named AP-PLA2-I and II) were purified from the crown
      of-thorns starfish (Acanthaster planci) venom. Both enzymes were confirmed to be
      PLA2s, based on the results that they showed hemolytic activity only in the
      presence of phosphatidylcholine (PC) and also released fluorescent fatty acids
      from PC with labeled fatty acids at the sn-2 position. The enzyme activity of
      both PLA2s was enhanced by Ca2+ but reduced by Cu2+ and Zn2+. The molecular mass
      of AP-PLA2-I was estimated to be 28 kDa by gel filtration and 15 kDa by SDS-PAGE,
      indicating that AP-PLA2-I is a dimer composed of the same subunit. In contrast,
      AP-PLA2-II was judged to be a monomer with a molecular mass of 12 kDa (gel
      filtration) or 15 kDa (SDS-PAGE). The amino acid compositions of the two enzymes
      were comparable to each other; Asx, Glx and Gly were rich in both molecules,
      while Met, His and Trp were poor. Analyses by a sequencer determined the first 62
      amino acid residues for both PLA2s. In the AP-PLA2-I preparation, minor amino
      acids were additionally found at 17 positions, suggesting the coexistence of
      another PLA2-component. As compared to the N-terminal sequences of the known
      PLA2s, both AP-PLA2-I and II were identified as class I enzymes not only because
      they have Cys-11 and lack Cys-51 but also because they contain the elapid loop in
      the region 53-61.

PMID- 9643472
TI  - Purification of a 5-HT uptake inhibitor from the venom of Cerastes vipera.
AB  - A protein that inhibits the re-uptake of 5-hydroxytryptamine into rat brain
      synaptosomes was isolated from the venom of the Sahara sand viper (Cerastes
      vipera) by gel filtration and reverse phase chromatography. It has a molecular
      weight of 13,739 Da and an IC50 of about 50 nM for blocking uptake of 3H-5-HT
      into rat brain synaptosomes. It also augmented the responses to 5-HT in a smooth
      muscle preparation. It has phospholipase A2 activity, but it has no lytic
      activity as measured by its inability to release lactate dehydrogenase from rat
      brain synaptosomes. Determination of the N-terminal sequence revealed a
      similarity with a phospholipase A2 previously isolated from Cerastes cerastes
      venom.

PMID- 9643473
TI  - Structures and biological activities of new wasp venom peptides isolated from the
      black-bellied hornet (Vespa basalis) venom.
AB  - The black-bellied hornet (Vespa basalis) is the most dangerous species of vespine
      wasps found in Taiwan. The hornet possesses a highly toxic venom which is rich in
      toxin, enzymes and biologically active peptides. Using ultrafiltration to remove
      the high molecular weight toxin and enzymes followed by reverse-phase HPLC, three
      bioactive tridecapeptides, designated "HP-1, HP-2 and HP-3" were isolated from
      the venom. Their amino acid sequences were determined as: HP-1: LFRLIAKTLGSLM, HP
      2: LFRLLANTLGKIL, HP-3: IFGLLAKTLGNLF. The primary structures of these peptides
      appear to be homologous to those of chemotactic peptides isolated from other
      vespid venoms. However, these peptides show little chemotactic activity on human
      neutrophils and have distinct tripeptide sequences at the amino and carboxylic
      terminal sides, as compared with other hornet chemotactic peptides. The lack of
      Pro3 which is a characteristic structure of vespid chemotactic peptides in their
      sequences is most distinctive. Circular dichroism spectra of these peptides
      measured in 20% trifluoroethanol show a high content of alpha-helical
      conformation. All three peptides provoked local edema in rat hind paw, which
      could be inhibited by antihistamine (diphenhydramine) and drug with antiserotonin
      activity (cyproheptadine). These peptides also exhibited a potent hemolytic
      activity which was potentiated by a non-lytic dose of the hornet lethal protein,
      suggesting a supporting role of these peptides in the lethal effect of Vespa
      basalis venom.

PMID- 9643474
TI  - Resistance of eels (Gymnothorax) to the venom of sea kraits (Laticauda
      colubrina): a test of coevolution.
AB  - Eels of the genus Gymnothorax from the Pacific are selectively preyed upon by
      banded sea kraits (Laticauda colubrina) and have been reported to sustain massive
      doses of sea krait venom without ill effect. By contrast, the present study found
      that Gymnothorax moringa from the Caribbean, where no sea snakes occur, are
      sensitive to sea krait venom, with doses as low as 0.01 mg dry wt of venom/kg wet
      wt of eel resulting in signs of envenomation, and doses as small as 0.1 mg/kg
      proving to be lethal. These observations suggest that the resistance of Pacific
      Gymnothorax to sea krait venom results from coevolution of predator and prey,
      rather than from a general hardiness of Gymnothorax. This theory is supported
      further by literature reports of sensitivity to sea snake venom by other taxa of
      non-coevolved eels that either are allopatric with sea snakes (Anguilla), or are
      sympatric with them but occupy different habitats and are not preyed upon by them
      (Heteroconger).

PMID- 9643475
TI  - Occurrence of a methyl derivative of saxitoxin in Bangladeshi freshwater puffers.
AB  - A new component of paralytic shellfish poison was isolated from a Bangladeshi
      freshwater puffer Tetraodon cutcutia. Its structure was deduced to be carbamoyl-N
      methylsaxitoxin based on electrospray ionization mass spectrometry, [1H] NMR, and
      conversion experiments.

PMID- 9643476
TI  - In vitro effects of smokeless tobacco extract on tumor necrosis factor-alpha (TNF
      alpha) and interleukin-1beta (IL-1beta) production, and on lymphocyte
      proliferation.
AB  - The use of smokeless tobacco (moist snuff) products is associated with mucosal
      lesions, gingival recession, attachment loss, and oral cancer. Despite numerous
      reports on the general toxic effects of smokeless tobacco extract, little
      information is available regarding the specific effects of smokeless tobacco on
      immune response. Inflammatory cytokines released as a result of smokeless tobacco
      induced irritation may play a role in the development of oral mucosal lesions at
      habitual tobacco placement sites in smokeless tobacco users. Consequently, the
      purpose of this study was to determine whether an aqueous extract of smokeless
      tobacco (STE) affects the secretion of tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1beta (IL-1beta), and the proliferation of lymphocytes. A macrophage
      cell line (J774-A1) was used to measure the effects of STE on tumor necrosis
      factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) secretion. Mouse
      splenocytes were used to assess the effects of STE on lymphocyte proliferation.
      We found that STE at low concentrations enhanced the production of both TNF-alpha
      and IL-1beta. Furthermore, STE at similar concentrations enhanced mitogen-induced
      murine splenocyte proliferation. Overall, these data suggest that smokeless
      tobacco upregulated two key proinflammatory cytokines and also induces lymphocyte
      proliferation.

PMID- 9643477
TI  - Isolation and characterization of an endogenous inhibitor of phospholipase A2
      from Indian cobra (Naja naja naja) venom.
AB  - A PLA2-inhibitor has been purified from Indian cobra (Naja naja naja) venom by
      the combination of ion-exchange and gel-filtration chromatography. The inhibitor,
      NN-I3 was a peptide with mol.wt 6500 and has a fluorescence emission maxima ca
      340 nm. NN-I3 specifically inhibited the enzyme activity of the three acidic PLA2
      from the same venom. The inhibition of NN-I2d-PLA2 and NN-I2c-PLA2 by NN-I3 was
      of mixed type and NN-I2c-PLA2 was of uncompetitive type. Neither the inhibitor
      nor the individual mixtures of acidic PLA2 with the inhibitor (1:1 w/w or 1:2
      mol:mol) were lethal to mice when injected intraperitoneally in doses up to 10 mg
      kg(-1) body weight.

PMID- 9643478
TI  - Brain neurotoxicity of Penitrem A: electrophysiological, behavioral and
      histopathological study.
AB  - The neurotoxicity of Penitrem A (PA) in rats was assessed against
      neurophysiological, behavioral and histopathological parameters. Animals were
      acutely given intracerebroventricular (22-45 mg) or intraperitoneal injections
      (0.5-1.5 mg/kg) of PA. A typical trembling syndrome associated with PA was always
      noted. Depending on the dose administered, animals may convulse and eventually
      die (1-1.5 mg/kg). PA-induced transient alterations of the EEG involving an
      increase in the frequency and voltage of electrical activity recorded from the
      cerebral cortex. Hippocampal activity was not modified and some pathologic
      activities may be recorded at the thalamus. Generally these EEG alterations
      disappeared at d 3 after the injection and the animals progressively recovered.
      However in the most severe cases, neuromotor disturbances were maintained at d 7
      (rotarod test). Coronal sections of the brain at the striatal, thalamic,
      hippocampal and pons levels mainly revealed that PA was able to induce dose
      related injuries in the cerebellum with massive degeneration of Purkinje cells
      and a significant vacuolization within the molecular layer. The neurotoxic
      mechanism remains unclear. Action of the mycotoxin on the cerebello-thalamo
      cortical tract is discussed.

PMID- 9643479
TI  - Effect of oral supplementation of vitamin E on the hemolysis and erythrocyte
      phospholipid-splitting action of cobra and viper venoms.
AB  - In the present investigation, it was found that oral supplementation of graded
      amounts of vitamin E to volunteers increased the alpha-tocopherol content of the
      erythrocytes and decreased the susceptibility of the latter to the hemolytic
      action of cobra and viper venoms. Further, exogenous addition of graded amounts
      of alpha-tocopherol to the red cells, prior to the addition of either venoms,
      minimizes the venom-induced lysis and erythrocyte phospholipid splitting. It may
      thus be inferred that vitamin E, a fat-soluble antioxidant, plays an important
      role in reducing the hemolytic action of cobra and viper venoms.

PMID- 9643480
TI  - Interactions between bacterial toxins and intestinal cells.
AB  - Bacterial toxins which act on intestinal cells display a great diversity of size,
      structure and mode of action. Some toxins interact with the cell by transducing a
      signal across the membrane leading to stimulation of intracellular second
      messenger (E. coli heat stable enterotoxin), others form pores (C. perfringens
      enterotoxin, ...) permitting the leakage of cellular components and cell lysis.
      The most sophisticated toxins comprise at least two functional domains or
      components, one being a binding domain permitting the internalization into the
      cell of an enzymatic domain which modifies an intracellular target. The enzymatic
      modification (ADP-ribosylation, UDP-glucosylation, glycohydrolysis, proteolysis,
      ...) of a specific target (heterotrimeric G-protein, small G-protein, monomeric
      actin, ribosomal RNA, ...) alters the cell physiology (increase of ions and water
      secretion, cytoskeleton rearrangement, protein synthesis inhibition, apoptosis,
      ...) and tissue organization (modification of barrier permeability, necrosis,
      ...). The study of bacterial toxins leads to the understanding of the
      interactions between pathogenic bacteria and their hosts and constitutes also a
      new approach in cell biology, by facilitating the exploration of certain
      regulatory pathways such as that controlling actin polymerization.

PMID- 9643482
TI  - Bibliography of toxinology.

PMID- 9643481
TI  - Inhibitory effect of habu antivenom on fibrinopeptide A release induced by
      Trimeresurus flavoviridis crude venom.
AB  - The correlation between the clotting activity of crude venom and concentration of
      fibrinopeptide A (FPA) released by the crude venom in rabbit plasma was evaluated
      and expressed as the coefficient of correlation (r = 0.850). The venom-induced
      FPA release was inhibited by habu antivenom. For such inhibition of FPA release,
      the correlation between the concentration of habu antivenom (Y) and that of crude
      venom (X) could be expressed by the equation Y = 7.115 + 0.709X. An absence of
      venom-induced FPA release in rabbit plasma had suggested that the clotting
      activity of crude venom could be neutralized by the habu antivenom. It is
      suggested that determinations of the FPA level in the plasma are effective in
      providing an indication of the reliability for serotherapy using habu antivenom.

PMID- 9643483
TI  - Fat necrosis in surveillance biopsies of heart transplants.
AB  - Fat necrosis was observed in surveillance biopsies of five patients following
      heart transplant. This reaction is poorly documented in the literature, but in
      personal communication, some pathologists working in the field have had
      experience with it. Four of the cases developed two to six days after
      transplantation, but in the fifth case, fat necrosis developed ten months after
      transplantation. Autopsy study of one case showed extensive severe fat necrosis
      involving both donor and recipient tissues. The cause is not known, and the
      changes are independent of rejection. However, the fat necrosis can be found
      within the interstitial tissues of the myocardium and subendocardium and may be
      mistaken for rejection if lymphocytes and polymorphs are part of the inflammatory
      response. The only clinical finding thought to be related to the fat necrosis was
      the development of transient complete heart block in a patient in whom the
      International Society for Heart and Lung Transplantation (ISHLT) standardised
      rejection grading was never greater than IA.

PMID- 9643484
TI  - Public attitudes towards the autopsy in China.
AB  - The autopsy rate in China has fallen within the last few years. The attitudes of
      the public have become an important factor for its decline. Attitudes towards
      autopsy were surveyed from 400 subjects residing in the 27 provinces of China.
      Among the 299 survey forms returned, 284 were completed correctly, the remaining
      15 being incomplete. The response rate was 71%. More than half of the responding
      members considered autopsy beneficial. However their perception of autopsy was
      quite inaccurate and prejudicial, lacking complete information. The two most
      frequent reasons for not accepting an autopsy were the lack of awareness towards
      the practice of autopsy and the wariness of body disfigurement after the autopsy
      was performed. It was suggested that the most appropriate way to change public
      perception of autopsy was through education. The primary tool for reaching the
      public was through the media. In addition, the approach to obtaining consent for
      autopsy should be improved.

PMID- 9643485
TI  - Intracranial epithelioid hemangioendothelioma arising at site of previously
      excised atypical meningioma.
AB  - Epithelioid hemangioendothelioma is an uncommon vascular tumor which, in most
      cases, pursues a clinical course intermediate between hemangioma and
      angiosarcoma. Only four completely documented cases of central nervous system
      involvement by this tumor appear in the literature. We present an additional
      case, which is remarkable in its occurrence at the site of a previously excised
      atypical meningioma and in its unusually aggressive clinical course. To our
      knowledge this is the first report of intracranial epithelioid
      hemangioendothelioma with postmortem documentation. The patient initially
      presented with a 7 cm right post frontal tumor; an atypical meningioma was
      excised and removal appeared complete on immediate post-operative scans. Seven
      months later the patient re-presented with tumor recurrence at the previous
      operative site; a second craniotomy was performed and, on this occasion, the
      excised tumor had the histological features of an epithelioid
      hemangioendothelioma without evidence of meningioma: both morphologically and
      immunohistochemically the two tumors were quite distinctive. Further recurrence
      prompted radiotherapy but the patient continued to deteriorate and died five
      months later. Massive recurrence of intracranial tumor was found at postmortem
      examination.

PMID- 9643486
TI  - The value of histological examination in the audit of hospital autopsies: a
      quantitative approach.
AB  - The aims of this study were to compare the clinical with autopsy diagnoses, to
      evaluate the role of histological examination in the pathological diagnoses and
      to assess the new pathological diagnoses uncovered by autopsy. We aimed to obtain
      quantitative assessment of the sensitivity, specificity and accuracy of clinical
      diagnoses. The guidelines for postmortem reports by the Royal College of
      Pathologists (1993) were implemented for reports used in this study. These
      guidelines are similar in intent to those of the College of American
      Pathologists. Complete macroscopic and histological studies of 108 (53 females)
      autopsies were analysed. The mean age was 78.0+/-9.0 (SD) years (range 54-94
      years). The interquartile range (25%ile 75%ile) was 72-84 years, with a median of
      79.5 years. Seventy per cent of all causes of death were confirmed by
      macroscopical and histological examination. Sixty-one clinical diagnoses were
      inconsistent with the pathological findings. Histological examination contributed
      significantly to the final diagnosis in major (5%) and minor (6%)
      clinicopathological as well as new pathological findings (23%). The most common
      causes of death not suspected clinically were pulmonary embolism (23%),
      bronchopneumonia (22%), ischemic heart disease (13%) and malignancies (10%). The
      clinical sensitivity of antemortem diagnoses was 25% for peritonitis and 24% for
      pulmonary embolism. The overall clinical sensitivity was 54% and specificity 92%.
      The accuracy of positive diagnosis was 69% and accuracy of negative diagnosis
      88%. Unexpected causes of death represented a third of all causes of death
      reported. Histological examination is an important tool in hospital autopsy
      audit. A quantitative approach can be used to assess the accuracy of postmortem
      clinical diagnoses, to identify the possible source of clinical diagnostic
      weakness, and provide data that may be of use for diagnostic precision in the
      more difficult clinical subjects.

PMID- 9643487
TI  - Tumor microvascularity has no independent prognostic significance for breast
      cancer.
AB  - There is a continuing controversy regarding the value of estimating degree of
      intra-tumor vascularity to predict prognosis in breast cancer. In order to
      resolve this controversy, primary tumors from a cohort of 519 women with breast
      cancer were analysed to determine whether association exists between degree of
      vascularity and prognosis. Tumor vascularity was estimated by
      immunohistochemistry using a monoclonal antibody to the antigen CD31. The tumor
      area showing the highest degree of vascularity was chosen to score the number of
      microvessels per unit area. Issues such as the reproducibility of the
      microvascularity score and its association with tumor parameters including size,
      histological grade and hormone receptor levels were investigated. Although
      previously agreed criteria were used, consensus between two pathologists'
      estimations of the degree of vascularity was only moderate. There was no
      statistically significant association between tumor vascularity score and other
      currently established parameters of prognosis. After a median follow up of 71
      months for axillary node negative patients, there was no association between
      tumor vascularity score and increased risk of relapse or death from breast
      cancer. In axillary node positive patients, tumor vascularity score was
      associated with increased risk of relapse and death from breast cancer. This
      association was not however independent of other established parameters of
      prognosis.

PMID- 9643488
TI  - Thymic carcinoma: spectrum of differentiation and histologic types.

PMID- 9643489
TI  - Atypical subcutaneous fatty tumors: a review of 37 referred cases.
AB  - We reviewed 37 referred, atypical, subcutaneous fatty tumors. There was a male
      preponderance (28:9). The median age was 51.5 years (26-83); the median duration
      of symptoms was 18 months (three weeks to 35 years); the median size was 5.5 cm
      (1.5-20) and the posterior cervico-dorsal areas (17 cases) was the commonest
      location. We divided tumors into five histological categories: (1) subcutaneous
      fibrolipomas with slight fibroblastic atypia (five cases); (2) subcutaneous
      spindle cell lipomas with atypia (mixed spindle cell/pleomorphic lipomas) without
      lipoblasts (three cases); (3) subcutaneous atypical well-differentiated fatty
      tumors (pure pleomorphic lipomas) without lipoblasts (nine cases); (4)
      subcutaneous atypical well-differentiated fatty tumors (pleomorphic lipomas) with
      lipoblasts (17 cases); (5) subcutaneous atypical fatty tumors with poorly
      differentiated or de-differentiated areas (three cases). Follow-up information
      was obtained in 25 cases (68%). The follow-up times were from three to 192 months
      (median 31). Five tumors (20%) recurred, two as the same and three as a higher
      histological category. Two were originally referred because of a recurrence. Four
      recurred once and one, initially a category 4 tumor, recurred twice as a category
      5 tumor. Two category 1 and three category 4 tumors recurred. There were no
      recurrences in the other three groups. All recurrent tumors were located outside
      the cervico-dorsal areas. The sizes of two tumors that recurred were 2.8 and 3 cm
      and the time to first recurrence was from one to 85 months. Two recurrent tumors
      of high histological category were controlled by re-excision and either
      radiotherapy or combined chemotherapy and radiotherapy. This series suggests that
      atypical subcutaneous fatty tumors comprise a continuous and potentially
      transforming histological spectrum, which ranges from mildly atypical
      fibrolipomas through various mixed spindle cell and pleomorphic lipoma patterns
      to tumors indistinguishable from de-differentiated liposarcomas. Despite a
      sometimes alarming histological appearance, none in the present series
      metastasized.

PMID- 9643490
TI  - Diagnostic value of p53 immunohistochemistry in Barrett's esophagus: an
      endoscopic study.
AB  - The aim of this study was to establish the diagnostic utility of p53
      immunohistochemistry in Barrett's esophagus. Three pathologists reviewed
      endoscopic biopsy specimens and one surgical specimen derived from 102 subjects
      in a prospective follow-up series. Dysplasia was graded as negative, indefinite,
      low grade and high grade. p53 staining was assessed as negative, weak or patchy
      and strong. Kappa coefficients for interobserver agreement for the three
      combinations of observer pairs were moderate to substantial (0.48, 0.55 and 0.68)
      for dysplasia and substantial to near perfect (0.77, 0.82 and 0.89) for p53
      immunostaining. In the consensus grading achieved for dysplasia, strong p53
      staining was recorded in 0/79 samples that were negative or indefinite for
      dysplasia, 5/15 (33%) examples of low grade dysplasia and 7/8 (87%) examples of
      high grade dysplasia. Non-dysplastic p53 positive glands were seen in specimens
      from two subjects harbouring dysplasia or cancer elsewhere. Two p53 positive
      specimens were, upon review and discussion, re-assigned from low- to high-grade
      dysplasia. It is concluded that p53 immunohistochemistry facilitates the
      interpretation of Barrett's epithelium but need only be employed to confirm a
      suspected diagnosis of dysplasia and assist with the distinction between low- and
      high-grade dysplasia.

PMID- 9643491
TI  - Broadsheet number 43: The role of the laboratory in the investigation and
      management of hyperuricemia.

PMID- 9643492
TI  - Broadsheet number 44: Rickettsial diseases: the Australian story so far.

PMID- 9643493
TI  - Test and teach. Number eighty seven: hepatic angiomyolipoma.

PMID- 9643494
TI  - Test and teach. Number eighty eight: alveolar capillary dysplasia.

PMID- 9643495
TI  - Test and teach. Number eighty nine: gastrointestinal autonomic nerve tumor
      (GANT).

PMID- 9643496
TI  - Aggressive natural killer cell leukemia/lymphoma.
AB  - A 32 year old Caucasian male presented with fever, massive hepatosplenomegaly and
      lymphadenopathy. Peripheral blood and bone marrow findings were consistent, both
      morphologically and immunophenotypically, with a natural killer cell
      leukemia/lymphoma. The disease was rapidly progressive and was fatal within five
      days after presentation.

PMID- 9643497
TI  - The prevalence and age distribution of human thymic B lymphoid follicles.
AB  - The reported prevalence of B lymphoid follicles in the normal human thymus
      differs widely between studies. In this histological study we have estimated the
      prevalence of these follicles, allowing for two factors which we believe may be
      largely responsible for such differences. One is the effect of stress of more
      than 48 hours duration, which has been shown to be associated with a decrease in
      prevalence, and the other is the considerable differences in prevalence found in
      different age groups. The 639 thymuses in this study were selected from
      individuals who died less than 48 hours after the onset of their fatal condition.
      No individuals with autoimmune diseases were included. The study group was
      divided into age groups to demonstrate the age related variations in prevalence.
      The follicles were identified by their morphology and by their reactivity with
      the B lymphoid cell marker L26. No follicles were found in the thymuses of
      infants in the first year of life. However the prevalence rose rapidly thereafter
      to a peak of 93% in individuals the first half of the second decade then
      gradually declined to only 9% in individuals older than 60 years. (The prevalence
      in young adults being approximately equal to that reported in young adults with
      autoimmune diseases.) It seems likely therefore that a considerable amount of the
      variation in prevalence found in previous studies is related to the inclusion in
      those studies of thymuses modified by stress as well as the grouping together of
      different age groups with differing naturally occurring prevalences of B lymphoid
      follicles. We concluded that B lymphoid follicles occur frequently in the
      thymuses of healthy individuals, that their prevalence varies considerably with
      age and that their mere presence should not be accorded any pathological
      significance.

PMID- 9643498
TI  - Detection and characterisation of extended spectrum beta-lactamases in Klebsiella
      pneumoniae causing nosocomial infection.
AB  - One hundred and ninety-five multi-resistant strains of Klebsiella pneumoniae were
      isolated at Princess Alexandra Hospital (PAH) between December 1991 and June
      1995. All these organisms produced extended spectrum beta-lactamases (ESBLs) as
      detected by the double disc synergy test (DDST). Between June 1994 and June 1995,
      a second population of 67 multi-resistant but DDST negative strains was isolated.
      Twenty multi-resistant Klebsiella pneumoniae strains (16 DDST positive and four
      DDST negative) and one susceptible strain were selected for further study. These
      were tested for production of ESBLs by two double disc synergy methods and agar
      dilution minimum inhibitory concentrations (MICs) with and without clavulanic
      acid. Detected ESBLs were further characterised by isoelectric focusing. The
      confirmed DDST positive K. pneumoniae strains all produced ESBLs that focused at
      an isoelectric point (pI) of 7.6, suggesting the presence of SHV-2, SHV-2a, SHV
      6, SHV-7 or SHV-8 enzymes. The multi-resistant DDST negative strains showed no
      clavulanic acid synergy and thus no evidence of the presence of ESBLs.

PMID- 9643499
TI  - Failure to detect Chlamydia pneumoniae in atherosclerotic plaques of Australian
      patients.
AB  - Chlamydia pneumoniae is a recently reported, but common, respiratory tract
      pathogen. The organism has been detected by electron microscopy,
      immunocytochemistry, polymerase chain reaction (PCR) and recently culture within
      atherosclerotic plaques, suggesting a possible association between C. pneumoniae
      infection and atherosclerosis. Interestingly this association has not been found
      by all researchers. We examined 17 carotid endarterectomy specimens, 16 carotid
      arteries and 16 coronary arteries from autopsy specimens. They were examined by
      PCR for the presence of C. pneumoniae. In none of the 49 atherosclerotic samples
      examined was C. pneumoniae detected. The sensitivity of our PCR assay was
      rigorously tested and found to detect consistently fewer than ten elementary
      bodies. The association between C. pneumoniae and atherosclerosis is intriguing
      but has not yet been demonstrated in Australian patients.

PMID- 9643500
TI  - Effect on organism recovery rate from BacT/Alert blood cultures with reduced
      incubation period.
AB  - This retrospective study evaluated 15,377 sets of BacT/Alert blood cultures to
      determine incubation time for blood cultures. Ninety-six per cent (1476) of total
      isolates signalled positive within five days and 56 isolates turned positive in
      five to seven days. Of the 56 organisms recovered between five and seven days, 49
      were considered contaminants and seven were considered clinically significant. On
      assessing the medical records of the patients with the seven clinically
      significant isolates, it was determined that the clinical outcome would not have
      changed if these isolates were missed. We conclude that a five day incubation
      protocol reduces the recovery of skin contaminants while not significantly
      decreasing the recovery of clinically significant organisms. The data suggest
      that the incubation time can be further reduced but this policy will depend on
      the individual institution and their patient population mix.

PMID- 9643501
TI  - An evaluation of the Behring Diagnostics Enzygnost Syphilis enzyme immunoassay.
AB  - The Enzygnost Syphilis (Behring Diagnostics, Marburg, Germany) was evaluated (i)
      using sera already characterised using the rapid plasma reagin test and the
      Treponema pallidum hemagglutination test (TPHA); (ii) prospectively; (iii) using
      sera which are recognised as causing "problems" with enzyme immunoassays. The
      Enzygnost Syphilis was found to have a reproducibility of 98.6% and a sensitivity
      of 99.5% using sera known to be TPHA-reactive. When tested prospectively, the
      false reactive rate was 3.2%. These results show that the assay performs
      sufficiently satisfactorily for its introduction as a screening assay for
      evidence of syphilis infection in our population.

PMID- 9643502
TI  - Evaluation of bacteriological transport swabs.
AB  - Ten commercial transport swabs were evaluated for their ability to preserve
      bacteria for 24 and 48 hours. Microorganisms included ATCC strains of Gram
      positive and Gram-negative aerobes and anaerobes. There was a wide variation in
      performance. Swabs using Amies plus charcoal medium or Stuart's medium had better
      recovery rates than those using Amies medium alone. The nature of the tips of the
      swabs had little influence. Performance was not correlated with cost of the
      swabs. These data will assist institutions to make cost-effective decisions when
      purchasing bacteriological transport systems.

PMID- 9643503
TI  - Comparison of culture, histopathology and urease testing for the diagnosis of
      Helicobacter pylori gastritis and susceptibility to amoxycillin, clarithromycin,
      metronidazole and tetracycline.
AB  - Gastric biopsy specimens were taken from 737 patients undergoing upper
      gastrointestinal endoscopy and assessed for Helicobacter pylori infection. The
      diagnostic utilities of H. pylori culture (733 patients), detection of urease
      production (724 patients) and histopathological examination (469 patients) were
      compared. Since each of these techniques may fail to diagnose patients infected
      with H. pylori, an attempt was made to estimate the true rate of infection using
      a mathematical approach that combined the results of culture, histopathology and
      urease testing; 34% of the 733 patients were thought to be infected. Using this
      figure as a benchmark, the sensitivity, specificity, positive predictive value
      and negative predictive value of H. pylori culture were 73.2%, 100%, 100% and
      86.3%, respectively, compared with 58.7%, 100%, 100% and 89.6%, respectively for
      urease production and 77.0%, 100%, 100% and 82.4%, respectively for
      histopathology. Thus, histopathological examination was the single most reliable
      test. A combination of histopathological examination and H. pylori culture
      diagnosed 99.5% of patients that were estimated to be truly infected. The minimum
      inhibitory concentrations of a number of antibiotics were measured for 135
      isolates of H. pylori. All isolates were susceptible to amoxycillin and
      tetracycline whereas 5.2% were resistant to clarithromycin and 60% were resistant
      to metronidazole.

PMID- 9643504
TI  - Detection of decreased penicillin susceptibility in viridans group streptococci.
AB  - One hundred consecutive clinically significant viridans group streptococcal
      isolates had their susceptibility to penicillin determined by the penicillin E
      test method. The ability of penicillin 2 and 10 unit disks and the oxacillin 1
      microg disk to detect reduced penicillin susceptibility, ie; MIC > or = 0.25
      microg/ml, in viridans group streptococci was determined by comparing the zone
      diameters against the penicillin E-test MICs. The sensitivity, specificity and
      predictive values of previous, existing and proposed interpretative criteria to
      detect decreased penicillin susceptibility were determined. Thirty-seven per cent
      of the isolates had reduced susceptibility to penicillin. The previous 1993 NCCLS
      interpretative criteria for the penicillin 10 unit disk, ie; resistant < or = 27
      mm failed to detect 16 of 37 (43%) isolates with reduced penicillin
      susceptibility. The 1 microg oxacillin disk using existing meningococcal
      interpretative criteria, ie; resistant < or = 10 mm, failed to detect 11 of 37
      (40%) isolates with reduced penicillin susceptibility. When the oxacillin 1
      microg disk pneumococcal interpretative criteria were used, ie; resistant < or =
      19 mm, all the isolates with reduced penicillin susceptibility were detected but
      42 of 63 (67%) susceptible isolates were misclassified as resistant. Based on our
      data, we set new interpretative criteria to detect all isolates with decreased
      penicillin susceptibility for each of the three disks. Using our proposed zone
      diameters to detect decreased penicillin susceptibility of < or = 27 mm for the
      penicillin 2 unit disk, < or = 35 mm for the penicillin 10 unit disk, and < or =
      17 mm for the oxacillin disk, 34 (54%), 44 (70%),and 21 (33%) of the 63
      susceptible isolates, respectively, were misclassified as having decreased
      penicillin susceptibility. Our data show that the oxacillin 1 microg disk is able
      to detect decreased susceptibility to penicillin in viridans group streptococci
      with greater specificity than either penicillin 2 or 10 unit disks.

PMID- 9643505
TI  - Hepatitis C genotyping by direct sequencing of the product from the Roche
      AMPLICOR test: methodology and application to a South Australian population.
AB  - The Roche AMPLICOR RT-PCR amplifies a 244 nucleotide sequence within the 5' non
      coding region (5'NCR) of the viral genome and is a widely used commercial test
      for the qualitative determination of hepatitis C RNA from sera. This paper
      describes a routine procedure for the purification of the PCR product, and its
      use in automated DNA sequencing, for determining the genotype of hepatitis C
      virus (HCV) isolates. Direct sequencing of the purified product was possible for
      86% of samples, whilst 14% required additional amplification using a nested PCR
      method in order to read the resulting electropherogram. This method of genotyping
      is considerably less expensive than currently available commercial kits, and is
      convenient for the increasing number of laboratories that have access to
      automated DNA sequencers. The highly conserved nature of the 5'NCR limited
      differentiation of types and subtypes to an extent comparable to commercial HCV
      typing methods. Using this method on available laboratory samples and on patients
      about to commence interferon therapy, we found a predominance of genotype 1 (59%)
      and 3a (31%). Analysis of data on the interferon patients showed the median
      length of time from first exposure to diagnosis to be significantly longer for
      patients with genotype 1 than genotype 3a.

PMID- 9643506
TI  - The molecular genetics of central nervous system tumors.
AB  - Over the past few years, although much has been learned about the molecular
      genetics of central nervous system (CNS) tumors, researchers and pathologists are
      only beginning to understand the scientific basis of the development of these
      tumors. Data accumulated so far support the division of glioblastoma into two
      clinical and molecular subsets. Primary or de novo glioblastomas occur in older
      patients, are clinically aggressive and exhibit epidermal growth factor receptor
      amplification or overexpression. Secondary glioblastomas develop from pre
      existing low-grade astrocytomas, have a more protracted clinical course, and
      frequently contain p53 mutations. Both types of tumors show deletions of
      chromosome 10 and possibly mutations of the PTEN/MMAC1 gene as an endstage event.
      Oligodendrogliomas have been shown to have genetic abnormalities distinct from
      those of the astrocytic tumors, commonly involving chromosomes 1p and 19q. As
      regards meningiomas, loss of chromosome 22q and mutations of the
      neurofibromatosis type 2 gene are frequent events and loss of chromosome 14q and
      10q may be seen in atypical or malignant transformation. Such genetic findings,
      apart from providing a better understanding of neoplastic transformation in brain
      tumors, are beginning to form the basis of a new approach to neuro-oncology.

PMID- 9643507
TI  - A mucosa-associated lymphoid tissue (MALT) type lymphoma (marginal zone B-cell
      lymphoma) from the palatine tonsil.
AB  - The clinicopathologic and immunologic features of a low-grade B-cell non
      Hodgkin's lymphoma that arose in the palatine tonsil are presented here. The
      histologic findings were similar to the mucosa-associated lymphoid tissue (MALT)
      type lymphoma described in the gastrointestinal tract and glandular tissues. The
      histogenesis, differential diagnoses and classification of these tumors are
      briefly discussed in the light of recent findings and proposals by the
      International Lymphoma Study Group (ILSG). A literature survey revealed that MALT
      lymphomas are exceptionally rare in Waldeyer's ring. Pathologists should be aware
      of the possible occurrence, albeit rare, of this tumor when confronted with a low
      grade B-cell lymphoma from Waldeyer's ring.

PMID- 9643508
TI  - Folliculosebaceous cystic hamartoma.
AB  - Although folliculosebaceous cystic hamartoma (FCH) is an uncommon cutaneous
      entity with distinct classical and variant histopathologic features, it lacks
      distinctive typifying clinical features. Since the original description of five
      cases of FCH by Kimura et al. in 1991, 12 cases have been documented. We report a
      further case of FCH presenting as facial lesion in a 35 year old African male.
      FCH comprises prominent epithelial and mesenchymal components. The epithelial
      component is characterised by folliculosebaceous proliferation with cyst-like
      infundibular dilatation, and the mesenchymal component exhibits variable
      fibroplasia, vascular and neural proliferation and adipocyte metaplasia.
      Awareness of the lesion is important to avoid confusion with other cystic or cyst
      like cutaneous lesions that contain prominent epithelial folliculosebaceous and
      variable mesenchymal components.

PMID- 9643509
TI  - Atypical cervical polyp with intracytoplasmic inclusions.
AB  - Benign polyps containing atypical stromal cells are described at many anatomical
      sites and some such lesions have been shown to contain intracytoplasmic actin
      rich inclusions, believed to represent deranged filament metabolism in
      proliferating myofibroblastic cells. We present a case of an atypical cervical
      polyp with intracytoplasmic inclusions, occurring in a 23 year old female, and
      provide support for the proposal that these inclusions are composed of actin
      filaments, identical to those initially reported in infantile digital
      fibromatosis. This report emphasises the need to recognise the benign nature of
      such stromal proliferations and expands the range of myofibroblastic lesions in
      which actin inclusions may occur. Characterisation of the inclusions will provide
      further insight into the complexities of actin metabolism.

PMID- 9643510
TI  - Intraductal carcinoma of the prostate metastatic to the penile urethra: a rare
      demonstration of two morphologic patterns of tumor growth.
AB  - Penile metastases from prostate cancer are rare and are usually a manifestation
      of wide-spread cancer dissemination. Isolated urethral metastases form a small
      fraction of these cases, have a longer survival rate and may represent spread by
      implantation following instrumentation. We report a case of prostatic carcinoma
      presenting with an isolated metastasis to the penile urethra after
      catheterisation and transurethral prostatectomy. The primary tumor had a
      prominent intraductal component whose architectural features were mimicked in the
      metastasis. The possible mechanisms of spread and the diverse appearances of
      cancer associated with an intraductal component are discussed.

PMID- 9643511
TI  - "Helicobacter pylori in areas of intestinal metaplasia in gastric antral mucosa",
      by Misra et al.

PMID- 9643512
TI  - Menopause, mood and hormone replacement therapy: methodological issues.
AB  - In this paper a number of methodological issues relating to research on the
      relationship between the menopause, mood and hormone replacement therapy (HRT)
      are discussed. These issues relate to problems of design and statistical
      analyses, problems which have prevented the reaching of definite conclusions
      regarding the relationship between menopause, mood and hormones. These problems
      are discussed under three main headings, namely, the assessment of menopausal
      status, statistical modelling and the design and analyses of clinical trials.
      Problems relating to concepts and measurement of dependent variables are the
      subject matter of the papers that follow. Within the three main headings more
      specific issues are detailed. The paper concludes with a list of recommendations
      on how research in this important area might be further advanced.

PMID- 9643513
TI  - The Blatt-Kupperman menopausal index: a critique.
AB  - The Blatt-Kupperman menopausal index has been used widely in studies of
      climacteric symptoms, but it now needs to be reassessed. The original index was
      derived from clinical experience in New York in the 1950s. The index was a
      combination of self report and physician ratings; it omitted measures of vaginal
      dryness and loss of libido; no demographic data of the sample were given;
      weighting was used without statistical justification; terms were ill defined;
      categories included overlapping scores, and most importantly scores were summed
      without being based on independent factors. Modern psychometrics has led to the
      publication of reliable and valid scales. These should be used in climacteric
      research in preference to the Blatt-Kupperman index.

PMID- 9643514
TI  - Constructing a standard climacteric scale.
AB  - Issues relating to the design of scales and their psychometric properties are
      discussed in the context of constructing a standard measure of core climacteric
      symptoms. Seven factor analytic studies of climacteric symptoms are examined to
      determine whether or not there is sufficient consensus across studies to permit
      agreement on the symptom content and the structure of such a scale. It is argued
      that these factor analytic studies do indeed contain sufficient consensus on the
      basis of which a standard climacteric scale can be constructed. Such a scale is
      described.

PMID- 9643515
TI  - The assessment of depression in peri-menopausal women.
AB  - This paper reviews research methods for detecting and assessing depressive
      symptoms in peri-menopausal women. The paper is written from the standpoint of
      clinical psychiatrists and clinical psychologists. Problems of method arise in
      two main areas: (i) the selection of population samples; (ii) the choice of
      methods for defining, detecting and measuring depression. An important
      distinction should be made between depressed mood and depressive disorder.
      Depressed mood is familiar sadness, low spirits, or despondency. Depressive
      disorder is a syndrome which is much more serious. The failure to make this
      distinction can detract from research findings. Standardised measures should
      always be used. These measures may be either self-rated or interviewer-rated. It
      is emphasised that the choice of these measures should be based on four
      characteristics: criterion overlap, sensitivity, test-retest reliability, and
      utility. The scales already available can be valuable provided that they are
      chosen carefully and with particular regard to these four qualities.

PMID- 9643516
TI  - Methods of assessing the impact of climacteric complaints on quality of life.
AB  - Quality of life is an important outcome that reflects the way patients feel and
      function. Assessing the impact of a condition on quality of life is particularly
      relevant in symptomatic conditions such as the menopause. A range of measurement
      tools are available for monitoring how symptoms, typical of the climacteric
      period, affect patients with regard to their well-being, sleep disturbance, other
      somatic symptoms, cognitive function and sexual functioning. However, to gain a
      valid assessment of quality of life and the effects of treatment in the
      menopause, only standard and well-validated measurement tools should be used. The
      appropriateness of relying on the use of psychiatric rating scales to assess mood
      is questionable. Results obtained from an increasing number of controlled
      clinical studies indicate that treatment with oestrogen, in addition to
      alleviating vasomotor symptoms, can substantially improve patients' quality of
      life.

PMID- 9643517
TI  - Methodological problems in the study of sexuality and the menopause.
AB  - Few studies have considered the effects of menopause on sexuality. Large studies
      with representative samples using postal questionnaires have included only a few
      sexual variables. More comprehensive studies have tended to employ non
      representative samples that raise questions concerning generalization of
      findings. Major problems in existing research have been: failure to collect data
      on variables known to affect sexuality and/or failure to utilize such data in
      analyses, studying only one, sometimes two, menopausal phases, gathering
      retrospective data, asking subjects directly about the relationship of menopause
      to sexuality, gathering too few sexual data, not providing a complete description
      of sexual measures, neglecting to report methodology clearly and completely,
      failing to evaluate data statistically, and inferring causation from
      correlations. Evidence from existing research suggests a decline in sexual
      interest, frequency of sexual intercourse, and vaginal lubrication in association
      with the menopause. Findings for variables such as capacity for orgasm,
      satisfaction with sex partner, and vaginal pain or discomfort are few and mixed.

PMID- 9643518
TI  - Aspects of progestin activity on the breast. European Progestin Club.
AB  - On 9-11 May 1997, the second Meeting of the European Progestin Club was held in
      Turin, Italy. Aspects of progestin use on the breast were discussed, based on the
      currently available scientific data. The paper covers topics addressed at the
      meeting and summarizes the recommendations which could be agreed on by the
      participants.

PMID- 9643519
TI  - Hormone replacement therapy usage: a 10 year experience of a solo practitioner.
AB  - The objective of this study was to identify factors affecting hormone replacement
      therapy (HRT) usage among patients of a single physician. All active patients (n
      = 330) given a HRT prescription over the past 10 years (1985-1995) by the
      physician were sent a questionnaire on health knowledge, lifestyle patterns,
      general medical and reproductive histories, responses to HRT usage and decision
      making about HRT use. A total of 214 useful questionnaires were returned giving a
      response rate of 65%. For this cohort, the length of HRT use for those still
      taking HRT was 60 months; and for those no longer taking HRT, it was 32 months;
      and 85% of those ever given an HRT prescription were still using HRT at the time
      of survey. The educational backgrounds, exercise patterns, health knowledge,
      medical and reproductive histories of this group were representative of those
      found among suburban postmenopausal women in central Pennsylvania. Among this
      cohort, the most important reason for them taking HRT was the physicians'
      recommendation.

PMID- 9643520
TI  - Facial wrinkling in postmenopausal women. Effects of smoking status and hormone
      replacement therapy.
AB  - BACKGROUND: There is some evidence that hormone replacement therapy may produce
      significant improvements in fine wrinkling, while aging skin is more frequently
      found in smokers. However, studies of the combined effect of a protective factor,
      such as HRT, and a damaging factor, such as smoking, are rare. OBJECTIVES: To
      determine in postmenopausal women the relationship between smoking status and the
      average number of packets of cigarettes since the subject took up smoking (packs
      years) on the one hand, and facial wrinkling on the other, and to evaluate the
      role of hormone replacement therapy in the prevention of wrinkles in smokers and
      non-smokers. METHODS: All subjects were recruited from our menopause clinic at
      Hospital Clinic i Provincial in Barcelona and were placed into one of three
      groups according to their smoking status: 215 life-long non-smokers, 306 former
      smokers and 209 current smokers. Smoking status, pack-years and hormone
      replacement were assessed by direct questioning. Facial wrinkle scores were
      estimated by standardized visual assessment. RESULTS: The relative risk of
      moderate-severe wrinkling for current smokers compared to that for life-long non
      smokers was 2.57 (confidence interval: 1.83-3.06; P < 0.0005). Pack-years was
      positively related to facial wrinkles. Life-long non-smokers receiving HRT had
      lower facial wrinkle scores than Life-long non-smokers who had never received
      HRT. HRT did not, in general, modify the facial wrinkle score in current smokers.
      CONCLUSION: Our results suggest that the risk of facial wrinkles is greater in
      smokers and that HRT does not diminish this risk.

PMID- 9643521
TI  - Sex-hormone binding globulin as an indicator of the hepatic impacts of continuous
      combined hormone replacement regimens.
AB  - OBJECTIVES: Nonoral administration of hormone replacement therapy avoids the
      first pass metabolism of steroids in the liver. We wanted to determine to what
      extent it has an effect on the serum concentrations of sex-hormone binding
      globulin and the free testosterone index. METHODS: Postmenopausal women received
      50 microg per day transdermal estradiol associated with the use of a
      levonorgestrel-releasing intrauterine device (20 women) or a daily oral dose of 2
      mg of estradiol and 1 mg of norethisterone acetate (20 women) for 1 year. Eight
      women, five in the nonoral and three in the oral therapy group discontinued the
      study. RESULTS: Although serum sex-hormone binding globulin concentrations
      decreased in women receiving transdermal estradiol in combination with a
      levonorgestrel-releasing intrauterine device, the free testosterone index did not
      change significantly. In the continuous oral regimen, no significant changes in
      serum sex-hormone binding globulin or free testosterone index were observed. The
      free testosterone index, however, was significantly higher in the nonoral therapy
      group after 6 and 12 months of treatment than in the oral therapy group.
      CONCLUSIONS: Continuous progestin combined with continuous estrogen in oral and
      nonoral replacement therapy does not lead to a substantial androgenic excess in
      postmenopausal women. The intrauterine administration of levonorgestrel appears
      to have some hepatic effect.

PMID- 9643522
TI  - Reduction of intraocular pressure in a glaucoma patient undergoing hormone
      replacement therapy.
AB  - OBJECTIVES: To show the reducing effect of estrogens and progestins on the
      elevated intraocular pressure (IOP) in the case of a 56-year-old woman showing
      typical climacteric complaints, who was admitted to the menopause outpatient
      unit. She also suffered from a primary open-angle glaucoma treated with
      betaophtiole eye drops with intraocular pressures of 16-20 mmHg under this local
      therapy. METHODS: IOP patterns were monitored by means of standardised daily
      pressure profiles four times a day before as well as 4 and 12 weeks after the
      beginning of hormone replacement therapy (HRT). The local glaucoma therapy
      remained unchanged. RESULTS: During HRT, IOP levels were reduced from 16-20 mmHg
      before therapy to 12-15 mmHg at week 4 and to 13-15 mmHg at week 12 after the
      beginning of HRT. CONCLUSION: The finding of a close chronological relationship
      between the onset of menopause and the development of a glaucoma is a potentially
      new indication for HRT.

PMID- 9643523
TI  - Multiple myeloma: VI International Workshop, June 14-18, 1997, Boston,
      Massachusetts, USA.
AB  - The VI International Workshop on Multiple Myeloma was organised by Professor
      Kenneth C Anderson, Dana Farber Cancer Institute, and held on June 14-18, 1997,
      in Boston, MA, USA. More than 500 participants from all over the world joined
      this workshop. Several subjects were introduced and one of the most exciting
      items of news was the identification of Kaposi's sarcoma-associated herpes virus
      in the bone marrow stromal cells of patients with MM. The aim of this overview is
      to give a glimpse of the subjects discussed and the statements made.

PMID- 9643524
TI  - Primary fallopian tube cancer: a review of the literature.

PMID- 9643525
TI  - Programmed cell death: the influence of CD40, CD95 (Fas or Apo-I) and their
      ligands.
AB  - Programmed cell death (PCD) or apoptosis is a process whereby developmental or
      environmental stimuli activate a specific series of events that culminate in cell
      death. PCD is essential for normal development and abnormality in the process can
      lead to defects ranging from embryonic lethality and tissue-specific perturbation
      of postnatal development to a high susceptibility to malignancy. Therapeutics
      that modulate the regulation of PCD may provide a new opportunity for the
      treatment of the PCD related diseases and cancer. CD40 and CD95 (Fas/Apo-I) are
      transmembrane proteins of the nerve growth factor/tumour necrosis factor alpha
      receptor superfamily. The death signal of PCD occurs when the CD95 receptor on
      the cell surface binds to the CD95 ligand (CD95L) or to the anti-CD95 monoclonal
      antibody (mAb). In contrast, PCD could be inhibited by the survival signal
      mediated from the binding of the CD40 receptor to the CD40 ligand (CD40L) or to
      the anti-CD40 mAb. In this review, the interaction of CD40/CD40L and CD95/CD95L
      on PCD in normal and malignant cells is discussed.

PMID- 9643526
TI  - How do mutated oncogenes and tumor suppressor genes cause cancer?
AB  - In recent decades we have been given insight into the process that transforms a
      normal cell into a malignant cancer cell. It has been recognised that malignant
      transformation occurs through successive mutations in specific cellular genes,
      leading to the activation of oncogenes and inactivation of tumor suppressor
      genes. The further study of these genes has generated much of its excitement from
      the convergence of experiments addressing the genetic basis of cancer, together
      with cellular pathways that normally control important cellular regulatory
      programmes. In the present review the context in which oncogenes and tumor
      suppressor genes normally function as key regulators of physiological processes
      such as proliferation, cell death/apoptosis, differentiation and senescence will
      be described, as well as how these cellular programmes become deregulated in
      cancer due to mutations.

PMID- 9643527
TI  - Treatment of chronic myelogenous leukaemia.

PMID- 9643528
TI  - Cancer morbidity in psychiatric patients: influence of lithium carbonate
      treatment.
AB  - The relationship between mental diseases and cancer development has been examined
      in a number of studies but the findings are still inconclusive and suffer from
      methodological problems. Studies conducted to examine the effect of lithium on
      malignant cells yielded inconsistent results. The study group included 609
      patients treated by lithium carbonate and 2396 controls. A lower but non
      significant risk (RR = 0.79; CI = 0.17-3.60) to develop non-epithelial tumors was
      found among lithium carbonate treated psychiatric patients as compared to
      controls. A significantly (P = 0.05) inverse trend of cancer with lithium dose
      was observed. The risk of cancer development among each group of psychiatric
      patients was significantly lower than in the general population (RR = 0.68 for
      the lithium treated group versus 0.78 for controls). Mental patients have a lower
      cancer prevalence than the general population and lithium may have a protective
      effect.

PMID- 9643529
TI  - Inhibition of systemic TNF-alpha cytotoxicity in cancer patients by D
      peptidoglycan.
AB  - The current study was designed to investigate direct inhibitory effects of N
      acetyl-glucosaminyl-muramyldipeptide (GMDP) over the cytotoxic nature of TNF
      alpha. A lactate dehydrogenase (LDH) assay of the inhibition of TNF-alpha
      cytotoxicity was done in vitro on the following cell lines: A549 (human lung
      carcinoma cells), A431 (human breast cancer cells) and L929 (mouse breast cancer
      cells). In a double-blind placebo-controlled trial, cancer patients with an
      elevated activity of all five LDH isoensymes were randomized to receive either a
      GMDP solution or a placebo; 63 patients were evaluated every third day for the
      mean daily number of episodes of nausea or vomiting, changes in clinical status,
      cell blood count and blood chemistry. A 95% inhibition of LDH release was noticed
      on A549 cells. Other cell lines were less sensitive to GMDP, with an observed 72%
      dose-dependent reduction in LDH activity. In vivo, LDH activity was decreased by
      41% (+/-4%) (mean+/-SD) in all 21 subjects who were given 0.5-1.0 mg of GMDP
      daily. A lowering of LDH activity by 73.4% (+/-4%) was observed in 23 patients
      who received GMDP at a dosage of 1.5mg/kg daily. Correspondingly, a 10% (+/-2%)
      increase in LDH activity was noticed in 19 patients who were given a placebo (P <
      0.01). During the follow-up period, the overall clinical condition of all
      patients treated with GMDP was improved. No side effects were observed. In nine
      patients who experienced nausea from tumor toxicity before treatment, the symptom
      subsided. In parallel, an extremely beneficial effect on lipids metabolism was
      noticed in all patients with elevated cholesterol and trigliceride levels. A
      dietary supplementation of GMDP has been shown to reduce systemic TNF-alpha
      cytotoxicity during tumor shock.

PMID- 9643530
TI  - Impact of histology on the treatment outcome of metastatic or recurrent renal
      cell carcinoma.
AB  - Among 107 renal cell carcinoma (RCC) patients with histopathologic subtype
      diagnosis who were treated at Albert Einstein Cancer Center with cytokines over a
      10-year period, seven patients had sarcomatoid histology, 63 had clear cell
      carcinoma, and 10 patients had mixed histology (sarcomatoid and clear cell).
      Regardless of their histology, patients with a disease free interval of 2 years
      or more had significantly better survival. None of the patients with sarcomatoid
      histology responded to therapy. However, several patients with mixed and clear
      cell histology achieved partial or complete responses following high dose
      Interleukin-2 (IL-2) therapy. The median survival of patients with sarcomatoid
      histology was the shortest (13.8 months), whilst that of patients with mixed and
      clear cell histology was much longer (34.8 months and 39.1 months, respectively).
      This result was statistically significant in both univariate and multivariate
      survival analysis (P < 0.001 and P < 0.01, respectively). Patients with mixed and
      clear cell histology had no significant difference in survival, and their median
      survival combined was significantly longer than that of patients with sarcomatoid
      histology (P < 0.0001 in univariate analysis, P < 0.01 in multivariate analysis).
      This study suggests that survival with a diagnosis of RCC is predicted by tumor
      histology and disease free interval, and this impacts on the ability to respond
      to standard therapy. Patients with mixed and clear cell histology respond to
      cytokine therapy. Other therapies should be sought for patients with sarcomatoid
      RCC.

PMID- 9643531
TI  - Saquinavir enhances the mucosal toxicity of infusional cyclophosphamide,
      doxorubicin, and etoposide in patients with HIV-associated non-Hodgkin's
      lymphoma.
AB  - Protease inhibitors are an important new class of agents for the treatment of
      human immunodeficiency virus (HIV) infection. The purpose of our trial was to
      determine the feasibility of combining the protease inhibitor saquinavir with a
      96-hour continuous intravenous infusion of cyclophosphamide (800 mg/M2),
      doxorubicin (50 mg/M2, and etoposide (240 mg/M2) (CDE) plus filgrastim in
      patients with non-Hodgkin's lymphoma associated with HIV infection. The effect of
      saquinavir on CDE-induced myelosuppression, CD4 lymphopenia, and non-hematologic
      toxicity was also sought. Twelve patients with HIV-related lymphoma received CDE
      every 28 or more days. All patients received saquinavir (600mg PO TID),
      filgrastim and Pneumocystis carinii and fungal prophylaxis. Patients also
      received either stavudine (n = 2) or both stavudine and didanosine (n = 10).
      Toxicity was analyzed using the NCI Common Toxicity Criteria for each cycle and
      the data were compared with the data from our prior study of CDE plus didanosine.
      An interim analysis was performed after accrual of the first 12 patients in order
      to assess toxicity. Severe (grade 3 or 4) mucositis occurred in eight of 12
      patients (67%) treated with CDE plus saquinavir compared with three of 25
      patients (12%) in our prior study treated with CDE without saquinavir (P <
      0.001). In logistic regression analysis, saquinavir use was the only factor
      associated with a significantly greater risk of severe mucositis (relative risk
      7.9; P = 0.03). Saquinavir use was not associated with a significant difference
      in the incidence of febrile neutropenia, prolonged neutropenia, chemotherapy dose
      reduction, or in the degree of myelosuppression. The decrease in CD4 lymphocytes
      for patients treated with saquinavir (absolute decrease of 23/microL, or a 26%
      decrease from baseline) was significantly less than for patients treated without
      saquinavir in the prior study (absolute decrease of 91/microL, or 42% decrease
      from baseline; P = 0.05). Four of 10 patients (40%) treated with saquinavir had
      an increase in CD4 lymphocytes of > or = 10/microL compared with none of 25
      patients (0%) treated without saquinavir (P < 0.001). Combination of the protease
      inhibitor saquinavir with infusional CDE in patients with HIV-associated lymphoma
      was associated with a significant increase in the incidence of severe mucositis.
      This finding suggests that saquinavir may alter the metabolism of one of more of
      the cytotoxic agents in the CDE regimen, and underscores the need for careful
      investigation regarding the use of the protease inhibitors in patients receiving
      chemotherapy.

PMID- 9643532
TI  - Severe hypercalcaemia and extensive osteolytic lesions in an adult patient with T
      cell acute lymphoblastic leukaemia.
AB  - Hypercalcaemia is a rare feature of acute lymphoblastic leukaemia (ALL) in
      adults, particularly of the T cell type. We report on a 24-year-old patient with
      T-ALL, who presented with symptoms of hypercalcaemia (vomitus, acute renal
      failure), bone pain, extensive osteolytic lesions and normal white cell count
      without circulating blasts. An increased serum tumor necrosis factor (TNF-alpha)
      concentration of 35 pg/ml was found; it remained elevated at 52 pg/ml four weeks
      later, after having achieved haematological remission. Serum concentrations of IL
      1beta, IL-6 and IL-2 were within the control range. The pathophysiology of
      hypercalcaemia in malignancy and possible mediators of bone resorption, in
      particular TNF-alpha, are discussed.

PMID- 9643533
TI  - Solitary primary CNS lymphoma: long term survival following total resection.
AB  - Primary non-Hodgkin's CNS lymphoma is rare, constituting 0.3-1.5% of all
      intracranial neoplasms in patients without AIDS. In the past 10 years the
      incidence has tripled in this population. The role of surgery is commonly limited
      to obtaining adequate tissue for diagnosis. This has precluded the evaluation of
      total surgical resection for a surgically accessible solitary lesion. We have
      encountered a 36-year-old healthy white male with primary CNS lymphoma who is HIV
      negative and who has survived over five years disease free after total surgical
      resection of his lymphoma.

PMID- 9643534
TI  - Successful treatment of cranial metastases of extrapulmonary small cell carcinoma
      with chemotherapy alone.
AB  - Extrapulmonary small cell carcinoma (EPSCC) is a distinct clinical and
      pathological entity other than small cell carcinoma of the lung. We present a
      case with EPSCC, with neurologic impairment due to brain metastases at initial
      diagnosis, which showed a complete response to combination chemotherapy. A 55
      year-old male patient was first admitted with a mass of 6 x 6 cm in diameter in
      the right cervical region. The diagnosis of small cell carcinoma was entertained
      with immunohistopathologic and light microscopic findings. During the period of
      investigation the tumor showed rapid progression and the patient had neurologic
      dysfunction with right hemiparesia, and papilla oedema in fundoscopy. Cranial CT
      showed supratentorial multiple cranial metastases and peritumoral oedema. Since
      the patient refused radiotherapy, combination chemotherapy was started (Etoposide
      100 mg/sq m i.v., days 1,3,5 and cisplatin 80 mg/sq m i.v., day 1). A fast
      response to the chemotherapy was observed with rapid disappearance of the
      cervical mass. Following six cycles of the chemotherapy the patient recovered
      fully and all the lesions disappeared with CT.

PMID- 9643535
TI  - Foetal liver infusion in a chronic myeloid leukemia patient with busulphan
      toxicity.
AB  - A 36-year-old man suffering from chronic myeloid leukemia (in chronic phase) was
      initially treated with busulphan. At the end of 6 months of follow-up he
      developed bone marrow aplasia. He was given single foetal liver infusion therapy.
      The patient recovered fully from aplasia. He continued in chronic phase for more
      than 7 years with intermittent busulphan therapy.

PMID- 9643536
TI  - TonB-dependent iron acquisition: mechanisms of siderophore-mediated active
      transport.
AB  - Cells growing in aerobic environments have developed intricate strategies to
      overcome the scarcity of iron, an essential nutrient. In gram-negative bacteria,
      high-affinity iron acquisition requires outer membrane-localized proteins that
      bind iron chelates at the cell surface and promote their uptake. Transport of
      bound chelates across the outer membrane depends upon TonB-ExbB-ExbD, a
      cytoplasmic membrane-localized complex that transduces energy from the proton
      motive force to high-affinity receptors in the outer membrane. Upon ligand
      binding to iron chelate receptors, conformational changes are induced, some of
      which are detected in the periplasm. These structural alterations signal the
      ligand-loaded status of the receptor and, therefore, the requirement for TonB
      dependent energy transduction. Thus, TonB interacts preferentially and directly
      with ligand-loaded receptors. Such a mechanism ensures the productive use of
      cellular energy to drive active transport at the outer membrane.

PMID- 9643537
TI  - In search of higher energy: metabolism-dependent behaviour in bacteria.
AB  - Bacteria use different strategies to navigate to niches where environmental
      factors are favourable for growth. Chemotaxis is a behavioural response mediated
      by specific receptors that sense the concentration of chemicals in the
      environment. Recently, a new type of sensor has been described in Escherichia
      coli that responds to changes in cellular energy (redox) levels. This sensor,
      Aer, guides the bacteria to environments that support maximal energy levels in
      the cells. A variety of stimuli, such as oxygen, alternative electron acceptors,
      light, redox carriers that interact with the electron transport system and
      metabolized carbon sources, effect changes in the cellular energy (redox) levels.
      These changes are detected by Aer and by the serine chemotaxis receptor Tsr and
      are transduced into signals that elicit appropriate behavioural responses.
      Diverse environmental signals from Aer and chemotaxis receptors converge and
      integrate at the level of the CheA histidine kinase. Energy sensing is widespread
      in bacteria, and it is now evident that a variety of signal transduction
      strategies are used for the metabolism-dependent behaviours. The occurrence of
      putative energy-sensing domains in proteins from cells ranging from Archaea to
      humans indicates the importance of this function for all living systems.

PMID- 9643538
TI  - Target specificity of insertion element IS30.
AB  - The Escherichia coli resident mobile element IS30 has pronounced target
      specificity. Upon transposition, the element frequently inserts exactly into the
      same position of a preferred target sequence. Insertion sites in phages, plasmids
      and in the genome of E. coli are characterized by an exceptionally long
      palindromic consensus sequence that provides strong specificity for IS30
      insertions, despite a relatively high level of degeneracy. This 24-bp-long region
      alone determines the attractiveness of the target DNA and the exact position of
      IS30 insertion. The divergence of a target site from the consensus and the
      occurrence of 'non-permitted' bases in certain positions influence the target
      activity. Differences in attractiveness are emphasized if two targets are present
      in the same replicon, as was demonstrated by quantitative analysis. In a system
      of competitive targets, the oligonucleotide sequence representing the consensus
      of genomic IS30 insertion sites proved to be the most efficient target. Having
      compared the known insertion sites, we suppose that IS30-like target specificity,
      which may represent an alternative strategy in target selection among mobile
      elements, is characteristic of the insertion sequences IS3, IS6 and IS21, too.

PMID- 9643539
TI  - The hexA gene of Erwinia carotovora encodes a LysR homologue and regulates
      motility and the expression of multiple virulence determinants.
AB  - We have identified a gene important for the regulation of exoenzyme virulence
      factor synthesis in the plant pathogen Erwinia carotovora ssp. carotovora (Ecc)
      and virulence and motility in Erwinia carotovora ssp. atroseptica (Eca). This
      gene, hexA (hyperproduction of exoenzymes), is a close relative of the Erwinia
      chrysanthemi (Echr) gene pecT and encodes a member of the LysR family of
      transcriptional regulators. hexA mutants in both Ecc and Eca produce abnormally
      high levels of the exoenzyme virulence factors pectate lyase, cellulase and
      protease. In addition, Eca hexA mutants show increased expression of the fliA and
      fliC genes and hypermotility. Consistent with a role as a global regulator,
      expression of hexA from even a low-copy plasmid can suppress exoenzyme production
      in Ecc and Eca and motility in Eca. Production of the quorum-sensing pheromone
      OHHL in Ecc hexA is higher throughout the growth curve compared with the wild
      type strain. Overexpression of Ecc hexA also caused widespread effects in several
      strains of the opportunistic human pathogen, Serratia. Low-copy hexA expression
      resulted in repression of exoenzyme, pigment and antibiotic production and
      repression of the spreading phenotype. Finally, mutations in hexA were shown to
      increase Ecc or Eca virulence in planta.

PMID- 9643540
TI  - Replication strand preference for deletions associated with DNA palindromes.
AB  - We have isolated and sequenced a set of deletions stimulated by DNA palindromes
      in Escherichia coli. All of the deletions are asymmetric with respect to the
      parental sequence and have occurred at short direct repeats. This is consistent
      with deletion by strand slippage during DNA replication. The orientation of the
      asymmetry in such deletion products is diagnostic of the direction of the strand
      slippage event. It is therefore also diagnostic of its occurrence on the leading
      or lagging strand of the replication fork when the direction of replication is
      known. In all cases in which the orientation of the asymmetry could be determined
      with respect to DNA replication, the products were consistent with a preference
      for deletion on the lagging strand of the fork. The data include replication
      slippage in three situations: on the chromosome of E. coli, in bacteriophage
      lambda and in high-copy-number pUC-based plasmids.

PMID- 9643541
TI  - Schizosaccharomyces pombe isp4 encodes a transporter representing a novel family
      of oligopeptide transporters.
AB  - We have recently cloned an oligopeptide transport gene from Candida albicans
      denoted OPT1. This gene showed significant sequence similarity to three open
      reading frames (ORFs) with no previously established function: isp4 from
      Schizosaccharomyces pombe and Saccharomyces cerevisiae YJL212C and YPR194C,
      identified during the genome project. The S. pombe gene isp4 was originally
      identified by Sato et al. as a gene that was upregulated through nitrogen
      starvation induction of meiosis. However, an isp4delta strain exhibited a wild
      type phenotype with respect to sexual differentiation. We have found that the
      same isp4delta strain is deficient in tetrapeptide transport activity as measured
      by its resistance to toxic tetrapeptides, by its inability to accumulate a
      radiolabelled tetrapeptide and by the inability to use tetrapeptides as a sole
      source of an amino acid to satisfy an auxotrophic requirement. Similarly, we
      found that the ORF YPR194C from S. cerevisiae encodes an oligopeptide
      transporter. Sequence analyses as well as physiological evidence has led us to
      propose that the proteins encoded by isp4 and the genes identified from S.
      cerevisiae and C. albicans comprise a new group of transporters specific for
      small oligopeptides, which we have named the OPT family.

PMID- 9643542
TI  - Involvement of two A-factor receptor homologues in Streptomyces coelicolor A3(2)
      in the regulation of secondary metabolism and morphogenesis.
AB  - Nucleotide sequences homologous to arpA encoding the A-factor receptor protein
      (ArpA) of Streptomyces griseus are distributed in a wide variety of
      streptomycetes. Two genes, cprA and cprB, each encoding an ArpA-like protein were
      found and cloned from Streptomyces coelicolor A3(2). CprA and CprB shared 90.7%
      identity in amino acid sequence and both showed about 35% identity to ArpA.
      Disruption of cprA by use of an M13 phage-derived single-stranded vector resulted
      in severe reduction of actinorhodin and undecylprodigiosin production. In
      addition, the timing of sporulation in the cprA disruptants was delayed by 1 day.
      The cprA gene thus appeared to act as a positive regulator or an accelerator for
      secondary metabolite formation and sporulation. Consistent with this idea,
      introduction of cprA on a low-copy-number plasmid into the parental strain led to
      overproduction of these secondary metabolites and accelerated the timing of
      sporulation. On the other hand, cprB disruption resulted in precocious and
      overproduction of actinorhodin. However, almost no effect on undecylprodigiosin
      was detected in the cprB disruptants. Sporulation of the cprB disruptant began 1
      day earlier than the parental strain. The cprB gene thus behaved as a negative
      regulator on actinorhodin production and sporulation. Consistent with this, extra
      copies of cprB in the parental strain caused reduced production of actinorhodin
      and delay in sporulation. It is thus concluded that both cprA and cprB play
      regulatory roles in both secondary metabolism and morphogenesis in S. coelicolor
      A3(2), just as the arpA/A-factor system in Streptomyces griseus.

PMID- 9643543
TI  - Inducer exclusion by glucose 6-phosphate in Escherichia coli.
AB  - The main mechanism causing catabolite repression by glucose and other carbon
      sources transported by the phosphotransferase system (PTS) in Escherichia coli
      involves dephosphorylation of enzyme IIA(Glc) as a result of transport and
      phosphorylation of PTS carbohydrates. Dephosphorylation of enzyme IIA(Glc) leads
      to 'inducer exclusion': inhibition of transport of a number of non-PTS carbon
      sources (e.g. lactose, glycerol), and reduced adenylate cyclase activity. In this
      paper, we show that the non-PTS carbon source glucose 6-phosphate can also cause
      inducer exclusion. Glucose 6-phosphate was shown to cause inhibition of transport
      of lactose and the non-metabolizable lactose analogue methyl-beta-D
      thiogalactoside (TMG). Inhibition was absent in mutants that lacked enzyme
      IIA(Glc) or were insensitive to inducer exclusion because enzyme IIA(Glc) could
      not bind to the lactose carrier. Furthermore, we showed that glucose 6-phosphate
      caused dephosphorylation of enzyme IIA(Glc). In a mutant insensitive to enzyme
      IIA(Glc)-mediated inducer exclusion, catabolite repression by glucose 6-phosphate
      in lactose-induced cells was much weaker than that in the wild-type strain,
      showing that inducer exclusion is the most important mechanism contributing to
      catabolite repression in lactose-induced cells. We discuss an expanded model of
      enzyme IIA(Glc)-mediated catabolite repression which embodies repression by non
      PTS carbon sources.

PMID- 9643544
TI  - Intramolecular synergism in an engineered exo-endo-1,4-beta-glucanase fusion
      protein.
AB  - Exoglucanase CelY and endoglucanase CelZ from the cellulolytic thermophile
      Clostridium stercorarium act in synergism to hydrolyse cellulosic substrates. To
      increase the efficiency of the hydrolytic degradation process, an artificial
      multienzyme carrying both enzymatic activities on one polypeptide chain was
      constructed by gene fusion. A segment of CelZ, CelZdeltaBB'C (designated CelZC'),
      comprising the catalytic domain and the adjacent domain C' homologous to the
      cellulose-binding domain family IIIc, was fused to the C-terminus of CelY,
      yielding the fusion protein CelY-CelZC', designated CelYZ. The large fusion
      protein (170 kDa) could be isolated from a recombinant Escherichia coli strain in
      its intact form retaining the pronounced thermostability of the fusion partners.
      As a true multienzmye, CelYZ exhibited both exoglucanase and endoglucanase
      activities. The cellulolytic activity of the fusion protein was three- to
      fourfold higher than the sum of the individual activities. Dilution experiments
      showed that the enhanced cellulolytic activity of the multienzyme resulted from
      intramolecular synergism of the fusion partners. The product profiles and the
      kinetic constants of cellulose hydrolysis support a new mechanistic model
      proposed for explaining the co-operativity of the two catalytic domains within
      the multienzmye.

PMID- 9643545
TI  - Antisense inhibition of expression of cysteine proteinases does not affect
      Entamoeba histolytica cytopathic or haemolytic activity but inhibits
      phagocytosis.
AB  - Inhibition of most of the expression of the cysteine proteinases of Entamoeba
      histolytica strain HM-1:IMSS was successfully performed by transcription of ehcp5
      antisense RNA using the promoter of ehg34, which encodes a L21 ribosomal protein
      of E. histolytica. We have generated a stable transfectant in which the overall
      level of cysteine proteinase activity is strongly reduced ( 90%). This
      transfectant has a normal growth rate in Diamond's TYI-S-33 medium, a cytopathic
      and haemolytic activity similar to the control HM-1:IMSS pEhAct-Neo transfectant
      but with a significantly lower phagocytic activity.

PMID- 9643546
TI  - Stress induction of the Bacillus subtilis clpP gene encoding a homologue of the
      proteolytic component of the Clp protease and the involvement of ClpP and ClpX in
      stress tolerance.
AB  - The Bacillus subtilis clpP gene, encoding the proteolytic component of the Clp or
      Ti protease, was cloned and sequenced. The amount of clpP-specific mRNA increased
      after heat shock, salt and ethanol stress, as well as after treatment with
      puromycin. Two transcriptional start sites upstream of the clpP structural gene
      were identified, preceded by sequences resembling the consensus sequences of
      promoters recognized by sigmaA and sigmaB transcriptional factors of the B.
      subtilis RNA polymerase respectively. Transcription initiation occurred
      predominantly at the putative sigmaA-dependent promoter in exponentially growing
      cells and was induced under stress conditions. After exposure to stress,
      initiation of transcription also increased at the sigmaB-dependent promoter, but
      to a lesser extent, indicating that clpP belongs to a double promoter-controlled
      subgroup of class III general stress genes in B. subtilis. In a sigB mutant
      strain, clpP remained heat and stress inducible at the sigmaA-dependent promoter.
      BgaB-reporter gene fusions, carrying either the sigmaA- or the sigmaB-dependent
      promoter, showed a higher bgaB induction at the sigmaA-dependent promoter,
      whereas a significantly lower level of induction was measured at the sigmaB
      dependent promoter. The sigmaA-dependent promoter appeared to be crucial for the
      heat-inducible transcription of clpP. A CIRCE (controlling inverted repeat of
      chaperone expression) element, the characteristic regulation target of class I
      heat shock genes such as dnaK and groESL, was not found between the
      transcriptional and translational start sites. Mutants lacking either the
      proteolytic component ClpP or the regulatory ATPase component ClpX were
      phenotypically distinct from the wild type. Both mutants produced chains of
      elongated cells and exhibited severely impaired growth under stress conditions
      and starvation. Comparison of two-dimensional protein gels from wild-type cells
      with those from clpP and clpX mutant cells revealed several changes in the
      protein pattern. Several proteins, such as GroEL, PpiB, PykA, SucD, YhfP, YqkF,
      YugJ and YvyD, which were found preferentially in higher amounts in both clpP and
      clpX mutants, might be potential substrates for the ClpXP protease.

PMID- 9643547
TI  - Polypeptide binding of Escherichia coli FtsH (HflB).
AB  - The Escherichia coli FtsH protein is a membrane-bound and ATP-dependent protease.
      In this study, we describe ATP-dependent conformational changes in FtsH as well
      as a polypeptide binding ability of this protein. A 33 kDa segment of FtsH became
      trypsin resistant in the presence of ATP. ATP and ATPgammaS prevented self
      aggregation of detergent-solubilized FtsH-His6-Myc at 37 degrees C, again
      suggesting that the binding of ATP induces a conformational change in FtsH.
      Affinity chromatography showed that FtsH-His6-Myc can associate with denatured
      alkaline phosphatase (PhoA) but not with the native enzyme. Denatured PhoA also
      prevented the aggregation of FtsH, and these two proteins co-sedimented through a
      sucrose gradient. Binding between FtsH-His6-Myc and detergent-solubilized SecY
      was also demonstrated. Although FtsH-bound SecY was processed further for ATP
      dependent proteolysis, FtsH-bound PhoA was not. Thus, FtsH association with
      denatured PhoA is uncoupled from proteolysis. Overproduction of FtsH
      significantly increased the cytoplasmic localization of the PhoA moiety of a MalF
      PhoA hybrid protein, in which a charged residue had been introduced into a
      transmembrane segment. Thus, denatured PhoA binding of FtsH may also occur in
      vivo.

PMID- 9643548
TI  - Targeted deletion and mutational analysis of the essential (2Fe-2S) plant-like
      ferredoxin in Synechocystis PCC6803 by plasmid shuffling.
AB  - The genes encoding (2Fe-2S) plant-like ferredoxins were studied in the widely
      used cyanobacterium Synechocystis PCC6803. The fedl gene (ssI0020) coding for the
      most abundant ferredoxin product was found to be expressed strongly as a light
      induced monocistronic transcript, whereas the other fed genes appeared to be
      silent (sIr1828) or moderately expressed as polycistronic transcripts regulated
      by either light fluence (sIr0150, negative control) or glucose availability
      (sII1382). fedl was found to be critical to Synechocystis PCC6803 viability in
      spite of sIr0150, sII1382 or flavodoxin induction, even after the addition of
      glucose that compensates for the loss of photosynthesis. Nevertheless, fedl could
      be deleted from all chromosome copies in cells propagating a fedl gene (even of
      heterologous origin) on a replicating plasmid. This strain was used as the host
      for the subsequent introduction of fedl mutant alleles propagated on a second
      vector. Analysis of the fedl mutant strains generated after plasmid exchange
      showed that the C18-C85 disulphide bridge is not central either to the tight
      compaction of ferredoxin I or to its reduction by photosystem I and demonstrated
      that the length of the Fedl carboxy terminus is important for effective PSI/FedI
      interactions. The plasmid-shuffling strategy presently described has general
      applicability for mutational analysis of essential genes in many organisms, as it
      is based on promiscuous plasmids.

PMID- 9643549
TI  - Lactococcus lactis phage operon coding for an endonuclease homologous to RuvC.
AB  - The function of the Lactococcus lactis bacteriophage bIL66 middle time-expressed
      operon (M-operon), involved in sensitivity to the abortive infection mechanism
      AbiD1, was examined. Expression of the M-operon is detrimental to Escherichia
      coli cells, induces the SOS response and is lethal to recA and recBC E. coli
      mutants, which are both deficient in recombinational repair of chromosomal double
      stranded breaks (DSBs). The use of an inducible expression system allowed us to
      demonstrate that the M-operon-encoded proteins generate a limited number of
      randomly distributed chromosomal DSBs that are substrates for ExoV-mediated DNA
      degradation. DSBs were also shown to occur upstream of the replication initiation
      point of unidirectionally theta-replicating plasmids. The characteristics of the
      DSBs lead us to propose that the endonucleolytic activity of the M-operon is not
      specific to DNA sequence, but rather to branched DNA structures. Genetic and
      physical analysis performed with different derivatives of the M-operon indicated
      that two orfs (orf2 and orf3) are needed for nucleolytic activity. The orf3
      product has amino acid homology with the E. coli RuvC Holliday junction
      resolvase. By site-specific mutagenesis, we have shown that one of the amino acid
      residues constituting the active centre of RuvC enzyme (Glu-66) and conserved in
      ORF3 (Glu-67) is essential for the nucleolytic activity of the M-operon gene
      product(s). We therefore propose that orf2 and orf3 of the M-operon code for a
      structure-specific endonuclease (M-nuclease), which might be essential for phage
      multiplication.

PMID- 9643550
TI  - Viral escape from antisense RNA.
AB  - RNA coliphage SP was propagated for several generations on a host expressing an
      inhibitory antisense RNA complementary to bases 31-270 of the positive-stranded
      genome. Phages evolved that escaped inhibition. Typically, these escape mutants
      contained 3-4 base substitutions, but different sequences were observed among
      different isolates. The mutations were located within three different types of
      structural features within the predicted secondary structure of SP genomic RNA:
      (i) hairpin loops; (ii) hairpin stems; and (iii) the 5' region of the phage
      genome complementary to the antisense molecule. Computer modelling of the mutant
      genomic RNAs showed that all of the substitutions within hairpin stems improved
      the Watson-Crick pairing of the stem. No major structural rearrangements were
      predicted for any of the mutant genomes, and most substitutions in coding regions
      did not alter the amino acid sequence. Although the evolved phage populations
      were polymorphic for substitutions, many substitutions appeared independently in
      two selected lines. The creation of a new, perfect, antisense RNA against an
      escape mutant resulted in the inhibition of that mutant but not of other escape
      mutants nor of the ancestral, unevolved phage. Thus, at least in this system, a
      population of viruses that evolved to escape from a single antisense RNA would
      require a cocktail of several antisense RNAs for inhibition.

PMID- 9643551
TI  - Domain structure and RNA annealing activity of the Escherichia coli regulatory
      protein StpA.
AB  - The Escherichia coli regulatory protein StpA bears striking similarity to the
      chromatin-associated protein H-NS. These two proteins have many structural,
      functional and mechanistic parallels. Although H-NS is more abundant in the cell,
      both proteins act as transcriptional regulators, both bind to curved DNA and both
      restrain DNA supercoils. However, StpA is better able to promote RNA annealing
      and trans-splicing in vitro. In this study, phylogenetic analyses and experiments
      to examine the protease sensitivity of StpA and H-NS suggest a similar structure
      for the two proteins. Both proteins consist of two structured domains separated
      by an exposed protease-sensitive linker. The N-terminal (StpA-NterL) and C
      terminal (StpA-CterL) domains of StpA, as well as the full-length StpA and H-NS
      proteins, were cloned, overproduced in E. coli and purified to homogeneity. StpA
      CterL, but not StpA-NterL, promotes strand annealing of complementary RNA
      oligonucleotides and in vitro trans-splicing of a model group I intron. Both StpA
      and StpA-CterL exhibited stronger RNA-modulating activity than H-NS. Phylogenetic
      analyses showed that the N-terminal and C-terminal domains can exist
      autonomously. The phylogenetic and experimental data are compatible with a two
      domain model for StpA and H-NS, with independently functioning modules joined by
      a non-conserved linker, and with the observed RNA-related activities residing
      entirely within the C-terminal domain.

PMID- 9643552
TI  - Supracriticality and the prion.

PMID- 9643553
TI  - Type III secretion in Chlamydia: a case of deja vu?

PMID- 9643554
TI  - Neural mechanisms underlying stereoscopic vision.
AB  - The progressive frontalization of both eyes in mammals causes overlap of the left
      and right visual fields, having as a consequence a region of binocular field with
      single vision and stereopsis. The horizontal separation of the eyes makes the
      retinal images of the objects lying in this binocular field have slight
      horizontal and vertical differences, termed disparities. Horizontal disparities
      are the main cue for stereopsis. In the past decades numerous physiological
      studies made on monkeys, which have in many aspects a similar visual system to
      humans, showed that a population of visual cells are capable of encoding the
      amplitude and sign of horizontal disparity. Such disparity detectors were found
      in cortical visual areas V1, V2, V3, V3A, VP, MT (V5) and MST of monkeys and in
      the superior colliculus of the cat and opossum. According to their disparity
      tuning function, these cells were first grouped into tuned excitatory, tuned
      inhibitory, near and far sub-groups. Subsequent studies added two more
      categories, tuned near and tuned far cells. Asymmetries between left and right
      receptive field position, on and off regions, and intra-receptive field wiring
      are believed to be the neural mechanisms of disparity detection. Because
      horizontal disparity alone is insufficient to compute reliable stereopsis,
      additional information about fixation distance and angle of gaze is required.
      Thus, while there is unequivocal evidence of cells capable of detecting
      horizontal disparities, it is not known how horizontal disparity is calibrated.
      Sensitivity to vertical disparity and information about the vergence angle or eye
      position may be the source of this additional information.

PMID- 9643555
TI  - Head direction cells and the neurophysiological basis for a sense of direction.
AB  - Animals require two types of fundamental information for accurate navigation:
      location and directional heading. Current theories hypothesize that animals
      maintain a neural representation, or cognitive map, of external space in the
      brain. Whereas cells in the rat hippocampus and parahippocampal regions encode
      information about location, a second type of allocentric spatial cell encodes
      information about the animal's directional heading, independent of the animal's
      on-going behaviors. These head direction (HD) cells are found in several areas of
      the classic Papez circuit. This review focuses on experimental studies conducted
      on HD cells and describes their discharge properties, functional significance,
      role in path integration, and responses to different environmental manipulations.
      The anterior dorsal thalamic nucleus appears critical for the generation of the
      directional signal. Both motor and vestibular cues also play important roles in
      the signal's processing. The neural network models proposed to account for HD
      cell firing are compared with known empirical findings. Examples from clinical
      cases of patients with topographical disorientation are also discussed. It is
      concluded that studying the neural mechanisms underlying the HD signal provides
      an excellent opportunity for understanding how the mammalian nervous system
      processes a high level cognitive signal.

PMID- 9643556
TI  - Cortical pathways to the mammalian amygdala.
AB  - The amygdaloid nuclear complex is critical for producing appropriate emotional
      and behavioral responses to biologically relevant sensory stimuli. It constitutes
      an essential link between sensory and limbic areas of the cerebral cortex and
      subcortical brain regions, such as the hypothalamus, brainstem, and striatum,
      that are responsible for eliciting emotional and motivational responses. This
      review summarizes the anatomy and physiology of the cortical pathways to the
      amygdala in the rat, cat and monkey. Although the basic anatomy of these systems
      in the cat and monkey was largely delineated in studies conducted during the
      1970s and 1980s, detailed information regarding the cortico-amygdalar pathways in
      the rat was only obtained in the past several years. The purpose of this review
      is to describe the results of recent studies in the rat and to compare the
      organization of cortico-amygdalar projections in this species with that seen in
      the cat and monkey. In all three species visual, auditory, and somatosensory
      information is transmitted to the amygdala by a series of modality-specific
      cortico-cortical pathways ("cascades") that originate in the primary sensory
      cortices and flow toward higher order association areas. The cortical areas in
      the more distal portions of these cascades have stronger and more extensive
      projections to the amygdala than the more proximal areas. In all three species
      olfactory and gustatory/visceral information has access to the amygdala at an
      earlier stage of cortical processing than visual, auditory and somatosensory
      information. There are also important polysensory cortical inputs to the
      mammalian amygdala from the prefrontal and hippocampal regions. Whereas the
      overall organization of cortical pathways is basically similar in all mammalian
      species, there is anatomical evidence which suggests that there are important
      differences in the extent of convergence of cortical projections in the primate
      versus the nonprimate amygdala.

PMID- 9643557
TI  - The regulation and biological activity of interleukin 12.
AB  - Interleukin 12 (IL-12) is a pleiotropic cytokine and mediates several biological
      activities on human T and natural killer (NK) cells, including induction of IFN
      gamma production, enhancement of cell-mediated cytotoxicity and comitogenic
      effects on resting T-cells. The major cellular sources producing IL-12 are
      antigen-stimulated monocytes, macrophages, and B-cells isolated from peripheral
      blood mononuclear cells (PBMC). Our laboratory has investigated the regulation of
      IL-12 gene expression in both cord blood and adult PBMC, and the effects of IL-12
      on induction of IFN-gamma production, NK, and lymphokine-activated killer (LAK)
      cytotoxicity. IL-12 mRNA expression and protein production in LPS-stimulated cord
      blood MNC were 3-4 fold decreased when compared with adult PBMC. There were no
      differences between cord blood and adult PBMC in both basal levels of
      transcription or the degree of transcriptional activation of the IL-12 gene.
      Additionally, the half-life of IL-12 p40 mRNA was 3-fold lower in activated cord
      blood compared to adult PBMC. Exogenous IL-12 induced a significant increase of
      IFN-gamma from both cord and adult PBMC. Cord MNC has significantly reduced
      levels of NK activity, and IL-12 significantly enhanced cord blood NK
      cytotoxicity up to similar levels in adult PBMC. IL-12 also significantly
      enhanced cord blood NK and LAK activities against a broad range of neuroblastoma,
      leukemia, and lymphoma cell lines. Lower doses of IL-12 and IL-15 concomitantly
      generated either synergistic or additive effects on cord blood NK and LAK
      cytotoxicities. In light of the important biological functions of IL-12, reduced
      expression and production of IL-12 from activated cord blood may contribute to
      the immaturity of cord blood cellular immunity and contribute, in part, to
      decreased severe graft vs. host disease following unrelated cord blood stem cell
      transplantation. IL-12 enhancement of IFN-gamma, NK, and LAK activity in
      activated cord blood MNC up to comparable levels in adult PBMC suggests that
      exogenous IL-12 stimulation can compensate for the immaturity in cord blood
      cellular immunity. These characteristics of IL-12 biological activity strongly
      suggest its potential usefulness in future cancer immunotherapy.

PMID- 9643558
TI  - Enhancement of adenovirus-mediated gene transfer to human bone marrow cells.
AB  - Adenovirus infection of CD34+ hematopoietic stem/progenitor cells is dependent on
      the multiplicity of infection (MOI), time of incubation, the volume in which the
      co-incubation occurs and the presence or absence of growth factors. Studies
      revealed that a brief co-incubation (1-8 hours), resulted in low levels of
      transgene expression, suggesting that adenovirus infection of CD34+ cells occurs
      slowly, and optimal transduction requires a 24 hour exposure to adenovirus.
      Infection by Ad/beta-gal or Ad/p53 at a MOI of 500:1 provided a high transduction
      efficiency but inhibited hematopoietic function. However, treatment at a MOI of
      50-100 resulted in efficient transduction (10.7-15.7% positive) without
      detectable toxicity. Secondary proof of adenovirus transgene expression was
      demonstrated by detection of mRNA for p53 in Ad/p53 infected stem cells. We
      conclude that a 24 hour exposure to recombinant adenovirus encoding p53 or beta
      gal, at a MOI of 50-100 is optimal for in vitro gene transfer to BM cells and has
      no significant effect on hematopoietic function. Adenovirus-mediated transduction
      of BM cells can also be modulated by growth factors (IL-3, GM-CSF and G-CSF) with
      improved gene delivery and maintenance of hematopoietic function. In summary,
      adenovirus vectors can be used to transiently transduce stem cells, and
      conditions have been defined to maximize expression and limit inhibitory effects
      on CD34+ cells. These data support continued investigation of this vector for
      local cytokine delivery and purging of stem cell products.

PMID- 9643559
TI  - Antitumor agent-induced apoptosis in myeloid leukemia cells: a controlled
      suicide.
AB  - Traditional antitumor research has generally believed that the cytotoxicity of
      antitumor agents was directly correlated with the amount of drug-induced cellular
      lesions. Accordingly, oncologists have tried to improve anticancer agent/target
      interactions by increasing the intracellular dose of active effectors. However, a
      growing body of evidence stemming from both clinical and experimental
      observations, strongly suggests that similar anticancer-induced lesions may
      result in different cellular responses, greatly influencing cytotoxicity. For
      example, it has been shown that in some but not all cellular models, antitumor
      agents trigger apoptosis, an irreversible process which leads to a rapid and
      complete elimination of tumor cells. Several of these studies also demonstrated
      that apoptosis induced by antitumor agents is highly regulated by multiple
      signaling pathways which are themselves influenced by oncogenes, protein kinase
      activities, external stimuli and the oxidative balance. Therefore, it appears
      that cell death commitment is controlled by both external and internal factors
      which interfere downstream of drug- or ionizing radiation-target interaction. The
      characterization of these mediators may provide novel strategies for modulating
      intracellular signaling pathways in order to promote apoptosis in drug-resistant
      tumor cells.

PMID- 9643560
TI  - Growth control mechanisms in multiple myeloma.
AB  - Interleukin-6 (IL-6) is the major growth factor for the malignant plasma cell
      clone in patients with multiple myeloma (MM). Although interferon-alpha (IFN
      alpha) has been widely used as maintenance therapy in MM, controversy exists as
      to its clinical utility. This review summarizes data showing that cell growth
      arrest brought about by type I (IFNs-alpha/beta) and type II (IFN-gamma) IFNs
      occurs in part through utilization/modification of various components of the
      otherwise stimulatory Jak-STAT and Ras signaling pathways triggered by IL-6.
      Recent experimental results indicating that IFN-alpha acts as a survival factor
      for certain myeloma cell lines and frequently induces endogenous IL-6 expression
      may help to explain the conflicting clinical findings obtained in this
      heterogeneous disease with this usually potent growth inhibitor. By comparison,
      consistent antiproliferative activity exhibited by IFN-gamma on IL-6-dependent
      myeloma cell lines and primary myeloma cells from patients suggests that further
      investigation of the possible value of this cytokine in the treatment of MM may
      be warranted.

PMID- 9643561
TI  - Developmental aspects of dendritic cells in vitro and in vivo.
AB  - Dendritic cells (DC) are potent antigen presenting cells that possess the unique
      ability to stimulate naive T-cells. By studying DC derived from various tissues
      it has been shown that the morphology, phenotype and function of DC alter as they
      undergo a complex process of maturation. DC are derived from bone marrow
      progenitors and circulate in the blood as immature precursors prior to migration
      into the peripheral tissues. Within tissues DC are specialised in the taking up
      and processing of antigen so that it may be presented on MHC class II molecules.
      Upon appropriate stimulation tissue DC undergo further maturation and migrate to
      secondary lymphoid tissue where they present antigen to T-cells and induce an
      immune response. Studies of DC maturation in vitro have defined the cytokines
      regulating their development from CD34+ myelomonocytic progenitors as well as
      from more mature peripheral blood precursors. An alternative pathway of
      differentiation from thymic precursors has also been described. As a result of
      these studies, DC may now be generated and manipulated ex-vivo for clinical
      applications in oncology, autoimmune disease and transplantation.

PMID- 9643562
TI  - EBV-NK cells interactions and lymphoproliferative disorders.
AB  - Epstein-Barr virus (EBV) usually infects epithelial cells in the oropharynx and B
      lymphocytes asymptomatically. Occasionally, however, EBV infects T-cells and
      natural killer (NK) cells, and infection of these cells has been associated with
      the development of leukemias and lymphomas. EBV-positive lymphoproliferative
      disorders of NK cells have been reported with increasing frequency, but the
      interactions between EBV and NK cells are not fully understood, in part because
      NK cells are not usually infected with EBV in vitro. The lymphoma-derived EBV
      positive NK cell line, YT, has been useful in the study of EBV infection of NK
      cells. YT cells express the EBV-associated nuclear antigen (EBNA)-1, the latent
      membrane protein (LMP)-1, and LMP-2A, but not EBNA-2 and LMP-2B genes. This
      pattern of latent gene expression is compatible with a type II latency program,
      normally associated with nasopharyngeal carcinoma, Hodgkin's disease, and T-cell
      lymphoma. In this report, we summarize recent information on EBV-NK cell
      interactions and EBV-positive lymphoproliferative disorders of NK cells.

PMID- 9643563
TI  - Parathyroid hormone-related protein in hypercalcemia associated with
      hematological malignancy.
AB  - Hypercalcemia is an important complication in multiple myeloma as well as T-cell
      leukemia/lymphoma, and is moderately common in high and intermediate grade non
      Hodgkin's lymphoma. The underlying mechanism has been unclear because the
      neoplastic cells are usually present in the bone marrow, where they are in a
      position to produce short range effects on bone resorption which are difficult to
      identify. This contrasts with the situation in hypercalcemia associated with non
      metastatic carcinoma, where it has been clearly demonstrated that the most common
      cause is release from the tumor of a humoral mediator, Parathyroid Hormone
      related Protein (PTHrP). Roles have been advocated in multiple myeloma for
      release of a number of other cytokines with osteolytic capacity on the basis of
      their enhancement of osteolytic activity in cultured fetal rat bone, although a
      causal relationship in patients has not been established. PTHrP has more recently
      been implicated in the genesis of hypercalcemia in patients with hematological
      malignancies by the demonstration in a proportion of cases of increased
      circulating levels of PTHrP, comparable to those in hypercalcemia due to cancer.
      Immunohistochemical studies indicate neoplastic hemopoietic cells can contain
      PTHrP, and thus have the capacity to act in a paracrine manner to enhance local
      bone resorption and contribute to the development of hypercalcemia.

PMID- 9643564
TI  - Genomic DNA amplification and the detection of t(2;5)(p23;q35) in lymphoid
      neoplasms.
AB  - Anaplastic large cell lymphoma (ALCL) is an intermediate grade Non-Hodgkin's
      lymphoma (NHL) characterized by the frequent presence of the t(2;5)(p23;q35).
      This translocation fuses the nucleophosmin (NPM) gene on chromosome 5q35 to a
      protein kinase gene (Anaplastic Lymphoma Kinase, ALK) on chromosome 2p23. In
      order to determine the frequency of t(2;5) we used a DNA polymerase chain
      reaction (PCR) amplification using genomic DNA, 5'-primers derived from the NPM
      gene, and 3'-primers derived from the ALK gene. The presence of amplifiable DNA
      in the samples was established with PCR and oligonucleotide primers designed to
      amplify a 3,016 bp fragment from the beta-globin locus. The t(2;5) PCR assay was
      established using DNA isolated from three t(2;5)-positive ALCL cell lines. Its
      ability to amplify genomic DNA prepared for routine molecular diagnostic use was
      validated using archival DNA from four ALCL tumors known to be t(2;5)-positive.
      Its sensitivity was established by serially diluting t(2;5)-positive DNA in
      normal DNA: amplicons were generated in 100% of reactions diluted 10(4)-fold (6-8
      cells per tube) and in 30% of those diluted 10(5)-fold (0.6-0.8 cells per tube.)
      We subsequently analyzed archival genomic DNA extracted from 38 ALCL, 77 NHLs, 37
      Hodgkin's lymphomas, and 9 lymphomatoid papuloses. The t(2;5) was detected in 6
      ALCLs (16%, 95% confidence intervals 6%-31%), but not in any other lymphoma, or
      in lymphomatoid papulosis. By using the published sequence of the fourth NPM
      intron that is involved in t(2;5) and by sequencing the individual tumor
      amplicons and also the normal ALK intron that is involved in t(2;5), we
      established that all breakpoints involve the same introns in the ALK and NPM
      loci. Detailed analysis demonstrated that each translocation generates a unique
      breakpoint sequence, and suggested that sequence homology between the ALK and NPM
      intron sequences may be involved in the translocation. We conclude that genomic
      DNA-PCR is useful for the detection of t(2;5) that in our patient population is
      restricted to ALCL and is not detectable in other NHL, Hodgkin's disease, or
      lymphomatoid papulosis. More work is needed to determine the prognostic
      significance of t(2;5), and to establish the utility of the genomic DNA PCR in
      monitoring minimal residual disease.

PMID- 9643565
TI  - Bone marrow involvement in lymphoma: the importance of marrow magnetic resonance
      imaging.
AB  - Detection of bone marrow involvement is important for staging and treatment
      decisions in patients with lymphoma. Although routine bone marrow evaluation is
      based on aspirates and bone marrow biopsies, new diagnostic tools are required to
      improve diagnostic accuracy. Visual and quantitative assessment of the bone
      marrow by magnetic resonance (MR) imaging is useful for the detection of occult
      lymphomatous marrow involvement. MRI is also suitable for the evaluation of
      disease extent in the bone marrow. Furthermore, abnormal images on marrow MRI may
      be associated with a significantly poorer survival in patients with lymphoma,
      regardless of histologic findings in the marrow. Evaluation of the bone marrow by
      MRI is essential to assess disease status in patients with lymphoma.

PMID- 9643566
TI  - Dyshematopoiesis in de novo acute myeloid leukemia: cell biological features and
      prognostic significance.
AB  - Dyshematopoiesis was found in 44 (42.3%) of 104 cases of de novo acute myeloid
      leukemia (AML). Dyshematopoietic AML (dys-AML) and AML without hematopoietic
      dysplasia (non-dys-AML) were compared with regard to biological, hematological,
      immunophenotypic, and cytogenetic parameters as well as prognostic criteria.
      Median age of patients was 55 years in both groups. In dys-AML, the median
      leukocyte count (p = 0.04), peripheral blast (p = 0.02) and medullary blast cell
      count (p < 0.001) were significantly decreased, whereas the median platelet count
      (p - 0.04) was increased. Immunophenotyping demonstrated that leukemic blast
      cells in dys-AML more frequently expressed the adhesion molcules CD54 (p = 0.05)
      and CD58 (p = 0.08) than leukemic cells in non-dys-AML. Cytogenetically, we
      distinguished two karyotypic patterns, one group with a normal karyotype or
      prognostically favorable single chromosome aberrations ("P(0)-karyotype"), and
      another one with unfavorable single aberrations or complex aberrations ("P(1)
      karyotype"). The incidence of these groups was not significantly different
      between dys-AML and non-dys-AML. Complete remission rate (CRR) after induction
      chemotherapy (p = 0.03) and overall survival time (OS; p = 0.03) were
      significantly lower in dys-AML. In addition, median disease free survival (DFS; p
      = n.s.) was inferior compared to non-dys-AML. In the dys-AML as well as in the
      non-dys-AML patient group, CRR, DFS, and OS were decreased in the P(1)-compared
      to the P(0)-subgroup. We conclude that dyshematopoietic AML is characterized by
      specific cell biological features and that hematopoietic and cytogenetic status
      represent complementary prognostic factors in de novo AML.

PMID- 9643567
TI  - Changes in the functional capacity of marrow stromal cells after autologous bone
      marrow transplantation.
AB  - Marrow stromal cells were evaluated several months after autologous BMT for their
      capacity to support both normal hemopoiesis and secrete the main growth factors
      involved in its control, G-CSF, GM-CSF, IL-3 and SCF. Stromal layers (SL) were
      obtained by long-term marrow cultures (LTMC) established from 15 patients (9 with
      hematologic malignancies and 6 with solid tumors) 3 months after autologous BMT
      and were compared to pre-graft patients. After irradiation, both post-graft and
      pre-graft SL were recharged with the same inoculum of normal marrow cells. As
      compared to pre-graft values, CFU-GM production on post-graft SL was
      significantly increased during the first 2 weeks of culture whereas it was
      decreased from week 3 to week 8. These findings were only observed in patients
      with hematologic malignancies and not in patients with solid tumors. Growth
      factor secretion was evaluated by ELISA in the supernatants of unstimulated and
      IL-1-stimulated SL from 10 post-graft patients, 13 pre-graft patients and 5
      normal controls. In any group of patients, IL-3 was undetectable either
      spontaneously or after IL-1-stimulation. As compared to controls, secretion by IL
      1-stimulated SL was not different for GM-CSF in pre- and post-graft patients but
      tended to be decreased for G-CSF in post-graft patients. SCF secretion, which was
      not induced by IL-1, appeared dramatically decreased in both pre- and post-graft
      patients. The capacity of post-graft SL to support CFU-GM growth in LTMC was
      correlated at week 1 with G-CSF secretion and from week 3 to week 8 with SCF
      secretion. These results suggest that microenvironment remains qualitatively
      damaged several months after BMT involving a decreased capacity both to support
      early hemopoiesis and to secrete SCF, particularly in patients grafted for
      hemopoietic malignancies.

PMID- 9643568
TI  - Expression of lung resistance protein and correlation with other drug resistance
      proteins and outcome in myelodysplastic syndromes.
AB  - The major vault lung resistance protein LRP is a cytoplasmic protein involved in
      drug resistance, especially in acute myeloid leukemia. We looked for LRP
      overexpression, using immunocytochemistry with LRP 56 monoclonal antibody, on
      marrow slides from 41 cases of myelodysplastic syndromes (MDS). LRP
      overexpression (LRP+) was defined by expression of LRP 56 in at least 20% of
      marrow blasts. LRP overexpression was seen in 19 (46%) cases. Concordant results
      between LRP overexpression and P-glycoprotein (PGP) expression were seen in 66%
      of the cases (p = 0.03), and discordant results (LRP+ and PGP-, or LRP- and PGP+)
      in 33% of the cases. No correlation was seen between LRP overexpression and FAB
      type, karyotype, CD34, p53 expression and bcl2 overexpression in blasts.
      Furthermore, in the 18 cases treated with anthracycline-AraC intensive
      chemotherapy and the 7 cases treated with low dose AraC, the response rate was
      not significantly different in LRP+ and LRP- patients. Survival was also similar
      in LRP+ and LRP- patients. In conclusion, LRP overexpression is probably more
      frequent in MDS than in de novo AML and, as in AML, is only partially correlated
      with PGP expression. In our experience, however, LRP was not a prognostic factor
      for response to chemotherapy and survival in MDS.

PMID- 9643570
TI  - Segmental jumping translocation in leukemia and lymphoma with a highly complex
      karyotype.
AB  - In order to identify the oncogene associated with malignant transformation 141
      leukemia and malignant lymphoma patients were studied by FISH. Specific
      chromosome regions were translocated onto structurally abnormal chromosomes,
      resulting in partial tri-, tetra-, or pentasomy of these regions. We designated
      this type of chromosomal translocation as a "segmental jumping translocation
      (SJT)". These SJTs were found in several chromosomal regions such as 8q24, 9q34,
      11q13, 11q23, 13q14, 14q24-q32, 21q22 and 22q11. The SJT at 9q34, which involved
      the ABL oncogene, was found in three of nine secondary leukemia patients who were
      treated with anticancer drugs and radiation. Non-Hodgkin's lymphoma and acute
      myeloid leukemia (AML) patients had 3-7 copies of SJT at 11q13 or 11q23. SJT at
      14q32 and 21q22 were predominantly detected in the acute type of adult T-cell
      leukemia (8 of 27 patients) and in AML (5 of 17 patients). The size of the SJT
      regions varied among the patients. The overlapping region within the SJT could
      involve oncogene(s) associated with transformation to the advanced stage in
      leukemia and lymphoma patients. The SJT provides evidence of a new mechanism for
      gene amplification and formation of unidentified marker chromosomes in the
      advanced disease stage.

PMID- 9643569
TI  - Minimal residual disease in acute myelogenous leukemia with PML/RAR alpha or
      AML1/ETO mRNA and phenotypic analysis of possible T and natural killer cells in
      bone marrow.
AB  - Here we studied minimal residual disease (MRD) of patients with acute myeloid
      leukemia (AML) who have PML/RAR alpha or AML1/ETO as well as the phenotypic
      analysis of lymphocyte subsets involved in antitumor immunity. Eight patients in
      long-term (LT; 3 to 15 years) and 15 patients in short-term (ST; up to 3 years)
      remission were studied. Using the reverse transcription-polymerase chain reaction
      (RT) assay, the limit of detection was 10(-5) to 10(-6) for PML/RAR alpha
      transcript and 10(-4) to 10(-5) for the AML1/ETO transcript. Simultaneously, T
      lymphocyte subsets and NK cells from the peripheral blood (PB) and bone marrow
      (BM) were investigated by flow cytometric analysis. Four of the eight patients in
      LT and 7 of the 15 patients in ST remission were MRD-positive. Although all MRD
      positive patients in LT remission are still until now event-free, 3 of the 7 MRD
      positive (MRD+) patients in ST remission soon relapsed. The total populations of
      CD4+, CD8+ and CD56+ [possible T-cell and natural killer (T/NK) populations] in
      the BM of ST patients and MRD+/LT patients were significantly (p < .01) low. The
      CD8+ CD28+ population showed the same tendency (p < .01-.02). The T/NK subsets in
      the BM of MRD-negative (MRD-) LT (MRD-/LT) patients showed similar numbers of
      cells as normal volunteers. Basically, the total percentage of the CD4+, CD8+ and
      CD56+ cell populations in the BM was increased and in the following order: MRD
      /LT patients, normal volunteers, MRD+/LT patients and MRD+ or -/ST patients. The
      percentages of the T/NK-cell subsets in the PB were not significantly different
      among these groups. Thus, the difference of the possible T/NK-cell phenotype in
      the BM may strongly influence clinical and molecular remission. These results
      still remain to be confirmed by further studies of the functional anti-tumor
      immunity of T/NK cells of AML in remission.

PMID- 9643571
TI  - Is multidrug resistance (P-glycoprotein) an intrinsic characteristic of plasma
      cells in patients with monoclonal gammopathy of undetermined significance,
      plasmacytoma, multiple myeloma and amyloidosis?
AB  - Multiple myeloma is not a curable disease, and most patients relapse after
      plateau phase. Drug resistance is a major problem in effective chemotherapy in
      this kind of disease. Current approaches are aimed at reversing or preventing
      drug resistance late in the disease. We studied a drug resistance marker, P
      glycoprotein (P-gp), in a total of 43 patients with monoclonal gammopathy. This
      group included eight with monoclonal gammopathy of undetermined significance
      (MGUS), five with plasmacytoma (PCM), nineteen with multiple myeloma (MM; six
      newly diagnosed, seven plateau, five refractory, one relapse) and eleven
      amyloidosis (seven newly diagnosed, four after treatment). Using 3-color flow
      cytometry, a plasma cell gate was selected on the basis of CD38+/45-(dim)
      staining and the population was examined for the expression of P-gp using two
      monoclonal antibodies (MRK16 and UIC2). P-gp expression was positive on marrow
      plasma cells in 42/43 patients. The resistance index (RI) in these cases (range
      2.0-7.07) is comparable to that in the positive cell line KG-1A (3.05-3.08). In 2
      of 5 patients with refractory MM, the RI for P-gp (5.4, 6.36) was higher than in
      plateau phase. These data suggest that relative resistance due to the P-gp
      mechanism is likely to be an intrinsic property of plasma cells in monoclonal
      gammopathies and may provide a partial explanation as to why these diseases
      always relapse. The results of our study support strategies for MDR reversal
      earlier in the course.

PMID- 9643572
TI  - Intravascular lymphomatosis--an indolent or aggressive entity?
AB  - Intravascular lymphomatosis (IVL) is a rare malignancy characterized by
      neoplastic proliferation of lymphoid cells within the lumens of arteries, small
      veins and capillaries. We report four patients with IVL and review the recent
      world literature, relating to incidence, clinical features and possible therapy.
      In these cases diagnosis was established coincidentally in one patient after
      prostatectomy. This patient eventually had central nervous system involvement. In
      two other patients IVL was diagnosed from skin lesions. In the fourth case the
      diagnosis was established at post-mortem examination, where involvement of most
      organs was evident but particularly kidneys, myocardium, gastrointestinal tract
      and lymph nodes. Therapy was given to three patients, but the disease progressed
      in two and they both died with evidence of central nervous system involvement,
      while the third patient has had a good partial response to combination
      chemotherapy but has relapsed within two months of completing chemotherapy. As
      evident from our patients and the literature review IVL has a variable clinical
      course and currently, there appears to be no effective therapy for this rare
      disorder.

PMID- 9643573
TI  - p53 mutation in a case of blastic transformation of follicular lymphoma with
      double bcl-2 rearrangement (MBR and VCR).
AB  - The bcl-2 gene is rearranged in most cases of follicular lymphoma and the
      breakpoint clusters are found in two specific regions: mbr and mcr.
      Rearrangements of the immunoglobulin heavy chain genes (IgH) result in a
      deregulation of the gene and increased transcription of mRNA for the bcl-2
      protein. In cases of rearrangement of the light chains (variant translocations),
      a third breakpoint has been described at the 5' part of the bcl-2 locus (vcr). In
      the present case, we report the molecular analysis of an FL transformed into a
      blastic phase unresponsive to chemotherapy. Molecular studies revealed a typical
      bcl-2 rearrangement at the major locus (mbr). Vcr rearrangements was also
      observed with only a single restriction enzyme. At the same time, SSCP analysis
      of exon 5 of the p53 locus disclosed an abnormal conformer. Direct sequencing
      revealed a point mutation at codon 163 (A --> G). Immunohistochemical analysis of
      the affected sites disclosed overexpression of p53 and bcl-2. It is concluded
      that p53 mutation can contribute to blastic transformation in cases of follicular
      lymphomas with double rearrangement at the bcl-2 locus (mbr/vcr).

PMID- 9643574
TI  - P53 gene mutation in a T-acute lymphoblastic leukemia cell line (loucy) with
      t(16:20) and 5q- chromosomal aberrations.
AB  - A human T-acute lymphoblastic leukemia (ALL) cell line (Loucy), derived from
      cells from a patient with resistant ALL with a t(16:20) and 5q- chromosomal
      aberrations was evaluated for p53 gene alterations and expression. Western blot
      analysis of p53 showed elevated levels of the protein. Reverse transcriptase
      polymerase chain reaction (RT-PCR) analysis and direct sequencing identified a
      point mutation at codon 272 (GTG --> ATG) of the p53 gene. Possible molecular
      mechanisms underlying these alterations and their role in the establishment of
      this cell line and in leukemogenesis in general are discussed.

PMID- 9643575
TI  - Spontaneous splenic rupture in a patient with acute lymphoblastic leukemia of
      Burkitt type.
AB  - We describe a case of spontaneous splenic rupture occurred in a patient with
      acute lymphoblastic leukemia of Burkitt type before starting cytotoxic
      chemotherapy. Left hypochondrial pain radiating to the homolateral shoulder was
      the only clinical symptom. Emergency computed tomography showed splenic
      laceration and hemoperitoneum. The patient underwent immediate laparatomy with
      splenectomy and experienced an uneventful postoperative recovery. Eight days
      after surgery, chemotherapy could be administered and complete remission was
      achieved. Although spontaneous rupture of the spleen is rare in leukemia and
      related disorders, this diagnosis should be taken in account also when clinical
      symptoms are mild. Following immediate operative management, patients may
      completely recover and receive cytotoxic chemotherapy with substantial
      possibilities of achieving complete remission.

PMID- 9643576
TI  - Dramatic resolution of pleural effusion in children with chronic myelomonocytic
      leukemia following short-course high-dose methylprednisolone.
AB  - High-dose methylprednisolone (HDMP) which can induce--differentiation and 
      apoptosis of myeloid leukemic cells has been shown to be very effective in the
      treatment of extramedullary infiltration (EMI) of children with acute
      myeloblastic leukemia (AML). In the present study 2 children with chronic
      myelomonocytic leukemia (CMML) who had pleural effusions were given a single
      daily dose of oral methylprednisolone (20 mg/kg or 30 mg/kg). In addition to
      dramatic improvement of respiratory symptoms, pleural effusions disappeared in
      four days in both patients possibly due to apoptotic cell death induced by HDMP
      treatment. Further studies are needed to determine whether high-dose
      corticosteroids are also effective on the resolution of pleural effusions
      associated with other malignant disease.

PMID- 9643577
TI  - Spontaneous acute tumor lysis syndrome in acute myeloid leukemia? A single case
      report with discussion of the literature.
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 following the treatment of various malignancies. However,
      only a handful of cases of spontaneous ATLS have been reported in the literature.
      We describe the first reported case of spontaneous ATLS in acute myeloid leukemia
      (AML). A previously healthy 63 year old woman presented with a two month history
      of fatigue and a one week history of easy bruising. On admission she had oliguric
      acute renal failure, with marked elevation in serum uric acid and phosphate. A
      bone marrow biopsy showed AML M7 with fibrosis. The renal failure resolved with
      supportive care and institution of allopurinol therapy. Following this, AML
      induction chemotherapy resulted in complete remission. Her biochemical and
      clinical course were very similar to the classical ATLS seen in patients after
      chemotherapy. Therefore, this case represents a rare instance of acute renal
      failure from spontaneous ATLS, and in our opinion the first reported occurrence
      of spontaneous ATLS associated with AML.

PMID- 9643578
TI  - Induction of apoptosis by bleomycin in resting and cycling human lymphocytes.
AB  - Bleomycin induces DNA and chromosome breakage. The differential sensitivity to
      the drug has been used in vitro to identify individuals at high risk of
      developing tumours. However, there are limited reports on the ability of
      bleomycin to induce apoptosis. In this study we tested induction of apoptosis in
      human peripheral lymphocytes by bleomycin at different concentrations and
      different culture times using various parameters, such as nuclear fragmentation
      and DNA fragmentation, evaluated either in situ with terminal transferase and
      labelled nucleotides (TUNEL) or by flow cytometry analysis. We demonstrate that
      bleomycin induces apoptosis without previous permeabilization of the cell
      membrane. Cell death occurs mainly by apoptosis and not by necrosis, with
      significant alteration of membrane lipoperoxidation (evaluated by luminescence).

PMID- 9643579
TI  - Frequency, distribution and clonality of chromosome damage in human lymphocytes
      by multi-color FISH.
AB  - Whole chromosome painting was used to determine whether the use of different sets
      of paints would influence results obtained from the analysis of human peripheral
      blood lymphocytes from 27 healthy unexposed subjects. Painting was also used to
      determine if aberration frequencies are proportional to the size of selected
      chromosomes in human lymphocytes irradiated in vitro. The in vitro results showed
      that the frequencies of radiation-induced stable aberrations (i.e. translocations
      and insertions) in chromosomes 3, 5 and 6 painted in unique colors are
      proportional to chromosome size. Aberration frequencies in the normal subjects
      were measured using two different sets of paints, one set for chromosomes 3, 5
      and 6 where each chromosome was labeled in a unique color and one set where
      chromosomes 1, 2 and 4 were painted in a single color. The frequency of
      aberrations among chromosomes 1-6 in the population as a whole was also found to
      be proportional to chromosome size. However, some individual subjects had a
      distribution of damage that was not proportional to chromosome size due to the
      presence of clones of abnormal cells. Aberration frequencies measured in
      chromosomes 3, 5 and 6 as a set were highly correlated with those observed in
      chromosomes 1, 2 and 4 as a set, after adjusting for the different amounts of the
      genome that were painted. We also determined whether differences exist in the
      aberration frequencies measured by two scoring systems: the classical method,
      where reciprocal exchanges are scored as single events, and PAINT, where each
      break junction is scored as a single event. The two scoring systems gave highly
      correlated results for translocations and differed by a constant value (PAINT x
      0.58 = classical method). Approximately 27% of translocations were observed to be
      non-reciprocal due to a failure to detect exchanges involving small amounts of
      material or to a non-reciprocal exchange mechanism. Our results support the
      hypothesis that cytogenetic evaluations for biodosimetry can be performed with
      any one or more of the chromosomes studied here and indicate that the aberration
      frequency measurements are independent of the scoring system selected for the
      evaluation. We also present a simple statistical method for identifying subjects
      that may possess clonal aberrations.

PMID- 9643580
TI  - Sodium arsenite-induced chromosomal aberrations in the Xq arm of Chinese hamster
      cell lines.
AB  - Non-cytotoxic concentrations (1.5, 3 and 6 microM) of sodium arsenite (SA) were
      used to study its cytogenetic effects with special reference to the frequency and
      nature of chromosomal aberrations on the X chromosome at Xq21 and at centromeric
      regions in CHO9, EM-C11, V79, V-H4 and CHE cell lines using Giemsa and FISH
      techniques. A high frequency of chromosomal breakpoints was distributed on the X
      chromosome localized at the secondary constriction region of the q arm (Xq21) and
      to a lesser degree at the centromeric region (c band-positive region), showing a
      high degree of fragility of these regions. This phenomenon was observed in all
      cell lines except for V79, where aberrations were localized only in the Xq21
      region, and CHO9, where the observed breakage frequency was lowest in comparison
      with other cell lines and breaks were mostly located in the centromeric region
      rather than at Xq21. Homozygous expression of the breakpoint at Xq21 (fragile
      site) and in the centromeric region was also confirmed using a female Chinese
      hamster embryonic (CHE) cell line, which showed a similar high frequency of
      breakpoints at Xq21 and in the centromeric region of both X chromosomes. Further,
      a detailed cytogenetic study in CHO9 and its ligase-deficient mutant EM-C11 cell
      line showed slightly higher sensitivity to SA in a cell survival assay. No
      difference was found for chromosomal aberrations in Giemsa stained preparations.
      For SCEs a higher spontaneous frequency was evident in EMC-11. SA significantly
      increased the frequency of SCEs in CHO9, but no effect was found in EM-C11.
      Further, we observed an increased number of abnormal cells with pulverised
      chromosomes, decondensed chromatin, isochromosomes and hyperploidy in CHO9 and EM
      C11 cell lines at all doses of SA.

PMID- 9643581
TI  - Frequencies of occurrence of all human chromosomes in micronuclei from normal and
      5-azacytidine-treated lymphocytes as revealed by chromosome painting.
AB  - Chromosome painting with library DNA probes specific for all human chromosomes
      was used to study the chromosomal content of micronuclei (MN) in normal and 5
      azacytidine (5-aza-C)-treated lymphocyte cultures. More than 60,000 normal
      lymphocytes were screened for associated MN after in situ hybridization. At least
      50 MN were scored for each probe. With the exception of chromosomes 12 and 19,
      which did not occur in MN, all other chromosomes were detected in MN at
      frequencies varying from 1 to 11.5%. Treatment of lymphocyte cultures with 5-aza
      C induced preferential exclusion of chromosomes 1 (34%), 9 (32%) and 16 (20%)
      material in MN, whereas chromosome 8, 10, 12-15 and 21 material was not detected
      in MN. The results obtained from normal lymphocytes allow for the first time an
      estimation of the frequency of occurrence of all chromosomes in spontaneously
      occurring MN in human cells. Data derived from 5-aza-C-treated lymphocytes are
      furthermore consistent with the view that undermethylation of heterochromatin may
      be associated with loss of specific chromosomes at metaphase.

PMID- 9643582
TI  - Influence of buthionine sulfoximine and reduced glutathione on arecoline-induced
      chromosomal damage and sister chromatid exchange in mouse bone marrow cells in
      vivo.
AB  - Arecoline (ARC), an alkaloid of the betel nut (Areca catechu), is a major
      ingredient of betel quid. The carcinogenic potentiality as well as its cell
      transformation ability has already been reported. Reduced glutathione (GSH), a
      major non-protein thiol substance plays an important role in protection of cells
      against the toxic effect of exogenous compounds. In order to understand the role
      of factors which affect ARC sensitivity, we have made an attempt to establish a
      relationship between ARC-induced DNA damage and the endogenous GSH status of the
      cells. ARC was administered to untreated and buthionine sulfoximine (BSO) (a GSH
      depleting agent)-treated mice. Exogenous GSH was also added to ARC-administered
      mice. Cells were fixed at 20 h and both chromosome aberrations (CAs) and sister
      chromatid exchanges (SCEs) were scored. Both CAs and SCEs were significantly
      induced by ARC and the frequency of both these parameters were increased further
      when ARC was given to BSO-treated mice. However, GSH reduced the frequency of CAs
      induced by ARC but failed to do so for SCEs. The data indicate that ARC-induced
      DNA damage is influenced by endogenous GSH level. The failure of GSH to reduce
      the frequency of SCEs indicates that the mechanism of induction of CAs and SCEs
      by ARC are different.

PMID- 9643583
TI  - Statistical analysis of lacZ mutant frequency data from MutaMouse mutagenicity
      assays.
AB  - Transgenic mouse assays have provided an unprecedented opportunity to study
      mutagenesis in diverse rodent tissues. In this article data from MutaMouse
      mutagenicity assays based on the Escherichia coli gene lacZ were analyzed
      systematically using liver and bone marrow as potential target tissues. Sources
      of variation, including plates (within packaging reactions), packaging reactions
      (within animals) and animals, were evaluated for extra-binomial variation.
      Although hardly any evidence of overdispersion was detected at the plate level,
      limited evidence of extra-binomial variation was observed at the packaging
      reaction level. There was, however, much stronger evidence of overdispersion at
      the animal level. Statistical tests for increasing trend in mutant frequency with
      increasing dose were also performed at the animal level. A significant increasing
      trend following exposure to N-nitrosodibenzylamine was detected in liver but not
      in bone marrow. A logistical model was used to further describe the dose-response
      relationship observed in N-nitrosodibenzylamine-treated liver tissue.

PMID- 9643584
TI  - Distribution of camptothecin-induced break points in Chinese hamster cells
      treated in late S and G2 phases of the cell cycle.
AB  - The distribution of camptothecin (CPT)-induced break points in late S or G2 phase
      of the cell cycle observed in Chinese hamster chromosomes was analysed in 400
      metaphases. Contrary to expectation, they were not localized in the
      heterochromatic regions, suggesting that these chromatid-type aberrations arise
      by a mechanism which does not involve collision of the CPT-trapped 'cleavable
      complex' with the replication fork. Since many break points mapped more
      frequently to light bands (DAPI negative) than dark bands (DAPI positive) with a
      frequency of 73 and 15% respectively, it could be argued that the presence of the
      CPT-trapped 'cleavable complex' probably interferes with chromatin condensation.
      In fact, the euchromatic regions, which are expected to be more actively
      condensed in G2 phase, were more involved in chromosomal damage. These results do
      not completely confirm the idea that some residual DNA synthesis occurring in G2
      is responsible for the G2 clastogenic effects of CPT as the heterochromatic
      regions should, in this case, be more involved.

PMID- 9643585
TI  - Expression of human cytochrome P450 1A2 in Escherichia coli: a system for
      biotransformation and genotoxicity studies of chemical carcinogens.
AB  - In this study we describe the development of strain BMX100, a new Escherichia
      coli K12 tester strain, derived from MX100, a strain which was constructed for
      detection of mutagens and for mechanistic studies of chemical carcinogens. We
      demonstrate here that strain BMX100 can be used for stable expression of human
      CYP1A2 or human CYP1A2 fused to rat liver NADPH cytochrome P450 reductase.
      Mutagenicity of precarcinogens known to be bioactivated by CYP1A2, namely 2
      aminoanthracene (2-AA), aflatoxin B1 (AFB1) and 2-amino-3-methylimidazo[4,5
      f]quinoline (IQ), could be detected. The mutagenic activity of 2-AA using BMX100
      expressing CYP1A2 alone and in combination with rat CYP reductase was
      respectively 10 and 20 times higher than in BMX100 with the standard metabolic
      activation system, rat liver S9 fraction. Furthermore, the mutagenicity of 2-AA
      could be nullified by alpha-naphthoflavone, a known inhibitor of CYP1A2. IQ
      responded equally in BMX100 expressing the CYP1A2-reductase fusion protein as
      compared with usage of rat liver S9 fraction. Rat liver S9 fraction was much more
      potent in generating a mutagenic response to AFB1 in BMX100 than in the strain
      expressing human CYP1A2 alone or CYP1A2 fused to rat reductase. The results
      described in this study demonstrate that this new E.coli strain can function as a
      human CYP1A2-competent prokaryotic mutagenicity test system and they seem to
      characterize BMX100 as a strain of interest for studies to identify individual
      human CYPs involved in bioactivation and bioinactivation reactions of putative
      genotoxins.

PMID- 9643586
TI  - Structural features of tannic acid important for DNA degradation in the presence
      of Cu(II).
AB  - Tannic acid has numerous food and pharmacological applications. It is an additive
      in medicinal products and is used as a flavouring agent and as an antioxidant in
      various foods and beverages. However, there are reports of its mutagenicity and
      carcinogenicity in bacterial and animal test systems. Tannic acid and its
      structural monomer gallic acid are also capable of inducing apoptosis in animal
      cells. We have earlier shown that tannic acid in the presence of Cu(II) causes
      DNA degradation through generation of reactive oxygen species such as hydroxyl
      radicals. In order to understand the chemical basis of the various biological
      properties of tannic acid we have studied the structure-activity relationship
      between tannic acid and gallic acid using the DNA cleavage assay. Results in the
      present paper indicate that gallic acid is considerably more active than tannic
      acid. However, if two of the three hydroxyl groups of gallic acid are methylated
      (syringic acid) the DNA degrading capacity declines sharply. Further,
      decarboxylation of gallic acid (pyrogallol) leads to enhancement of its activity.
      In conclusion, the results indicate that the DNA cleavage activity of tannic acid
      is due to its digalloyl moeity and that free hydroxyl groups are essential for
      cleavage.

PMID- 9643587
TI  - Structural and numerical chromosomal aberrations in a metabolically competent
      human lymphoblast cell line (MCL-5).
AB  - MCL-5 cells are Epstein Barr virus-transformed human lymphoblasts which have been
      genetically engineered for use in mutagenicity testing. We have examined the
      modal chromosome number, karyotype and spontaneous micronucleus (MN) and sister
      chromatid exchange (SCE) frequencies of the cell line. Replicate experiments were
      conducted on two different shipments purchased from Gentest Corp. Although the
      modal chromosome number was 48 (range 40-54, n = 400 metaphases) for both cell
      shipments, the second stock showed greater variation in chromosome number than
      the first. A total of 60 G-banded metaphase cells was analyzed and seven
      karyotypes were prepared. Consistent structural abnormalities (translocations,
      deletions and isochromosomes) were found involving the X chromosome and seven
      autosomes (1-3, 5, 6, 9 and 11). The karyotype typical of this cell line was:
      48,der(X)t(X;?)(p22.3;?)Y,t(1;2)(q23;p23),del(3)(q12q21), + i(3q),t(5;6)
      (q31;p23),+i(9p),der(11)t(11;13)(q23;q12). The mean MN frequency was 41.8 MN/1000
      binucleate cells (n = 5000). When compared with our historical controls for
      primary lymphocyte cultures this number (41.8) is significantly (8.4-fold)
      higher. The mean SCE frequency was 7.3 per metaphase (n = 100). We observed a
      hyperdiploid chromosome number of 48 in the majority of metaphase spreads,
      indicating a significant deviation from the normal diploid number characteristic
      of the parent cells (RPMI 1788) established in 1969. The variation in chromosome
      number distribution observed between shipments suggests the potential for further
      changes. The elevated MN frequency suggests that evaluating mutagenicity using
      this cytogenetic end-point may require excessive dosing to produce a significant
      response over background. We conclude that careful interpretation of cytogenetic
      end-points is necessary when using MCL-5 cells in the light of the possibility of
      clonal evolution presented here.

PMID- 9643588
TI  - Heterogeneity of the DNA damage provoked by antimony and arsenic.
AB  - Data on the mechanism of antimony genotoxicity is scarce. Arsenic and antimony
      are proposed to share some toxicological features. Thus comparative and combined
      experiments with As(III) and Sb(III) were performed to gain a deeper knowledge of
      the mechanism of antimony genotoxicity. Trivalent arsenic proved to be five times
      more cytotoxic and one order of magnitude more potent in induction of micronuclei
      in human lymphocytes in vitro than was antimony. Significantly increased
      micronucleus frequencies were achieved with As(III) at a dose of 0.5 microM and
      with Sb(III) at a dose of 5 microM. Neither the number of micronuclei induced by
      As(III) nor by Sb(III) could be suppressed by co-incubation with superoxide
      dismutase or catalase. This suggests that induction of oxidative stress may not
      be a crucial step in the mechanism of DNA damage induction by arsenic and
      antimony. The combined genotoxicity in micronucleus test co-incubation
      experiments with arsenic and antimony seemed best described by simple additivity.
      In the single cell gel test with human lymphocytes a significant induction of DNA
      damage was observed with 0.01 microM As(III) and 5 microM Sb(III). In contrast to
      Sb(III), As(III) proved to be a very potent inducer of DNA-protein crosslinks. It
      may be that Sb(III) as well as As(III) causes DNA damage by inhibition of enzymes
      involved in DNA repair. Further investigations will have to identify the relevant
      sites of action.

PMID- 9643589
TI  - Genotoxic lipid peroxidation products: their DNA damaging properties and role in
      formation of endogenous DNA adducts.
AB  - The peroxidation of polyunsaturated lipids generates a range of substances that
      possess DNA damaging potential. This includes lipid hydroperoxides and various
      species that contain unpaired electrons, such as the alkoxyl and peroxyl
      radicals. In addition, a range of genotoxic carbonyl-containing compounds are
      formed, such as malondialdehyde, various 4-hydroxy-2-alkenals such as 4
      hydroxynonenal and a number of 2-alkenals. It has previously been assumed that
      the antioxidants and electrophile scavenging enzymes existing in mammalian cells
      effectively protect the genetic material against these substances. However,
      thanks to recent analytical advances in the detection of low levels of DNA
      adducts, it is now evident that DNA adducts formed from a range of lipid
      peroxidation products are abundant in both rodent and human genomes. This
      suggests that the cellular defence system is not 100% efficient and that a
      proportion of endogenously produced lipid peroxidation products escape
      detoxification and cause DNA damage. This review surveys the genotoxic properties
      of the major classes of lipid peroxidation products, focusing on their chemistry
      of DNA adduction, the mutagenic properties of such damage and the evidence that
      it occurs in intact biological systems. Furthermore, avenues of future research
      that will clarify the significance of such damage to spontaneous mutagenesis and
      carcinogenesis are proposed and discussed.

PMID- 9643590
TI  - Cleft care: life after CSAG. Clinical Standards Advisory Group.

PMID- 9643591
TI  - Human recombinant BMP-2 in osseous reconstruction of simulated cleft palate
      defects.

PMID- 9643592
TI  - Functional treatment of craniosynostoses during childhood.
AB  - The aim of this article was to present a treatment strategy for complex
      craniosynostoses, such as Apert syndrome and Crouzon's disease, based on the
      author's experience of over 16 years. The most favourable results of primary
      decompression have been achieved by the radical osteoclastic procedure described
      by Powiertowski. Subsequent frontal advancement and Le Fort III osteotomy are
      necessary in these patients when they reach 6-10 years of age. Orthopaedic
      treatment with a Delaire mask should be started immediately after the operation
      to achieve optimal growth of the skull base with anterior rotation of the maxilla
      and posterior rotation of the mandible, which leads to a much better result.

PMID- 9643593
TI  - Head and neck cancer services: views of patients, their families and
      professionals.
AB  - OBJECTIVES: To explore views of patients, their families and professionals about
      head and neck cancer services. METHODS: Focus group interviews of 33 patients and
      relatives and 33 professionals from four hospitals and two patient support groups
      in SouthEast England. RESULTS: Although patients and relatives were grateful for
      their care, many thought that some areas could be improved. Many thought that
      their ward facilities were inappropriate. Patients wanted to have more
      information about the impact of their treatment and about different treatment
      options whereas professionals tended to concentrate on giving information about
      the details of operations. Counselling services were often found to be
      inaccessible and inappropriate. Administrative difficulties were a major source
      of frustration for professionals, as were failure of treatment and communication
      difficulties. Professionals valued joint clinics and a team approach in keeping
      up to date, in clinical decision making, and in providing mutual support.
      CONCLUSION: The findings highlight areas that could be improved which would
      benefit both patients and professionals.

PMID- 9643594
TI  - Cross-matched blood for major head and neck surgery: an analysis of requirements.
AB  - We retrospectively analysed our blood ordering practice; the number of units of
      cross-matched blood requested was compared with the number transfused, in 70
      patients undergoing a total of 82 ablative operations for malignant disease.
      Patients undergoing neck dissection alone, or excision of tumour with free
      revascularized flap reconstruction without neck dissection, are unlikely to
      require blood transfusion. Operations that include excision of tumour with
      primary closure and neck dissection, excision of tumour with pedicled flap
      reconstruction and excision of tumour with any form of flap reconstruction and
      neck dissection in continuity, will probably require transfusion. If atypical
      antibodies are present in the patient's serum on screening, cross-matched blood
      should always be available preoperatively. Provided that atypical antibodies are
      not present and that blood is available within 40 minutes from the blood bank,
      our results show that it is safe to adopt a policy of blood grouping and saving
      serum, for patients undergoing neck dissection alone, but cross-matching two or
      more units of blood for patients who are to have more extensive operations.

PMID- 9643595
TI  - Dental extractions in patients on warfarin: is alteration of anticoagulant regime
      necessary?
AB  - Various clinical protocols for the management of warfarinised patients needing
      dental extractions have been suggested. This study was designed to compare two
      approaches in the management of these patients. A control group of 32 patients
      had their warfarin treatment stopped for 2-3 days prior to having dental
      extractions, resulting in a reduction in the average preoperative international
      normalised ratio (INR) from 2.6 to 1.6. The study group of 33 patients did not
      have their anticoagulant treatment altered before extractions, and had an average
      preoperative INR of 2.7. All patients were treated under local analgesia on an
      outpatient basis, and local measures-consisting of Surgicel pack and sutures-were
      used in all cases to control postoperative bleeding from extraction sockets. None
      of the patients had any immediate postoperative bleeding, and only 1 patient from
      each group had mild delayed haemorrhage, which was easily controlled with local
      measures. It is proposed that, provided the INR is within the therapeutic range
      of 2.0 to 4.0 and local measures are used to control postoperative bleeding,
      there is no justification in altering warfarin treatment prior to dental
      extractions in these patients, and thereby exposing them to the risk of
      thromboembolism.

PMID- 9643596
TI  - von Willebrand disease and its management in oral and maxillofacial surgery.
AB  - von Willebrand disease (vWD) is the most common of the hereditary disorders of
      coagulation. We describe the pathophysiology, diagnosis and the new simplified
      classification of the disorder and discuss the management of patients about to
      undergo dental procedures and maxillofacial surgery. Close collaboration between
      oral and maxillofacial surgeons and haematologists in the management of patients
      with vWD is essential.

PMID- 9643597
TI  - Atypical cervico-facial mycobacterial infections in childhood.
AB  - We describe three patients who presented with atypical mycobacterial infection.
      Although antituberculous drugs are ineffective, combination treatment with
      clarithromycin or amikacin and ciprofloxacin (with or without cotrimoxazole)
      leads to eventual resolution of the lesions. The treatment of choice, however,
      remains complete excision of the affected area which obviates the need for
      prolonged chemotherapy and minimizes the scarring which may otherwise develop
      after conservative treatment.

PMID- 9643598
TI  - Five-year results of maxillary intramobile Zylinder implants.
AB  - We retrospectively analysed the time-dependent function of 501 Intramobile
      Zylinder (IMZ) implants inserted between August 1983 and December 1994 to restore
      partially and fully edentulous maxillae. To ensure the independence of implants
      when calculating level of significance, we chose one implant per patient at
      random. This was done 500 times to obtain a representative result. The simplified
      success rate was 473/501 (92%) whereas the time-related survival probability was
      76% after 60 months. In 31% (156/500) of the life-table calculations, implants
      placed in completely edentulous maxillae showed a significantly lower probability
      of survival than did those placed in partially edentulous patients (P mean: 0.17;
      SD: 0.19). Implants, that had been placed in the anterior and premolar regions of
      edentulous maxillae, had a survival probability of 60%, after 60 months. The
      survival probability of implants placed in the molar region was 100%, over the
      same observation period. The patient's age, sex, and the time of placement of the
      implant after tooth extraction had no significant influence on the implant's
      prognosis. The prognosis of implants inserted for partial edentulism meets the
      criteria proposed for a viable implant system. Our findings indicate that in
      complete edentulous maxillae, implants should be placed in the posterior rather
      than in the anterior region, even though this necessitates augmentation
      procedures such as sinus lift.

PMID- 9643599
TI  - Desmoplastic variant of ameloblastoma in Chinese patients.
AB  - Desmoplastic ameloblastoma is a rare tumour, and we know of only 43 previously
      reported cases. We report seven Chinese patients (five men and two women) with
      the desmoplastic variant of ameloblastoma, which makes up 9% of all
      ameloblastomas diagnosed during the years 1981-1995. The age ranged from 18 to 68
      years (mean 43). Five of the tumours were in the maxilla and two were in the
      mandible. Five of them were situated anteriorly, the remaining two cases
      involving both anterior and posterior maxilla. The features of the 42 cases
      previously reported were reviewed and were compared with those in the present
      study. Our results differ in that we found a male predominance, wider age range
      and more tumours in the maxilla. Histologically, this variant of ameloblastoma is
      characterized by abundant collagenous stroma. Because the epithelial clusters may
      show prominent squamous metaplasia or may be compressed into thin strands in most
      areas, the appearance may mimic a squamous odontogenic tumour or odontogenic
      fibroma. The behaviour of this variant of ameloblastoma is likely to be the same
      as that of the classic ameloblastoma.

PMID- 9643600
TI  - Simple X-ray film holder for lateral view of the anterior jaws using dental X-ray
      apparatus.
AB  - A new X-ray apparatus, the occlusal X-ray film holder, was devised so that the
      lateral view of the jaw could be studied. This apparatus could easily be adjusted
      to a dental X-ray cone. In 21 cases of impacted teeth, cysts or foreign body in
      the maxilla and mandible and 6 cases that necessitated examination before or
      after implantation, the efficacy of this apparatus was confirmed. Its advantages
      are: it is applicable to dental X-ray equipment; it is cheap; there is no need
      for image intensifying to get a clear image; and follow-up examination is
      possible. We believe that this film holder would be useful for the diagnosis of
      lesions in the anterior maxilla and mandible as well as in the general dental
      clinic.

PMID- 9643601
TI  - A recessively inherited non-lethal form of popliteal pterygium syndrome.
AB  - Two siblings, a 10-year-old boy and a 6-month-old girl, born in a Palestinian
      family, with manifestations of popliteal pterygium syndrome are presented. This
      rare form of syndrome is usually assumed to be autosomal dominant. Parental
      consanguinity and lack of phenotype manifestation in the ancestry of the present
      family favoured an interpretation of determination by an autosomal recessive
      trait.

PMID- 9643602
TI  - Latex foam and staple fixation of skin grafts.
AB  - Skin grafts are time consuming to secure effectively. We report our experience
      with a simple, versatile and rapid technique utilising staples and a latex foam
      dressing.

PMID- 9643603
TI  - Combined use of titanium mesh and biocompatible osteoconductive polymer in the
      treatment of full thickness calvarial defects.
AB  - Restoration of bony defects is a common problem in craniofacial surgery. This
      article describes a versatile approach using a combination of titanium micromesh
      or midimesh and biocompatible osteoconductive polymer to restore calvarial bone
      loss.

PMID- 9643604
TI  - Prevention of microstomia following facial burns.

PMID- 9643605
TI  - Citation for the Down Surgical Prize 1996 to Richard Haskell.

PMID- 9643606
TI  - Citation for the De Puy Surgical Prize 1996 to Mike Corrigan.

PMID- 9643607
TI  - Isolated incident involving an assault with a bamboo cane.

PMID- 9643608
TI  - Combined radial forearm and pharyngeal flaps for soft palate reconstruction.

PMID- 9643609
TI  - Failed pharyngoplasty.

PMID- 9643610
TI  - Protection of the lingual nerve.

PMID- 9643611
TI  - Pharmacovigilance: towards the next millennium.

PMID- 9643612
TI  - Use of the UK General Practice Research Database for pharmacoepidemiology.
AB  - The last decade has seen a surge in the use of computerized health care data for
      pharmacoepidemiology. Of all European databases, the General Practice Research
      Database (GPRD) in the UK, has been the most widely used for
      pharmacoepidemiological research. Since 1994, this database has belonged to the
      UK Department of Health, and is maintained by the Office of National Statistics
      (ONS). Currently, around 1500 general practitioners with a population coverage in
      excess of 3 million, systematically provide their computerized medical data
      anonymously to ONS. Validation studies of the GPRD have documented the recording
      of medical data into general practitioners' computers to be near to complete. The
      GPRD collects truly population-based data, has a size that makes it possible to
      follow-up large cohorts of users of specific drugs, and includes both outpatient
      and inpatient clinical information. The access to original medical records is
      excellent. Desirable improvements to the GPRD would be additional computerized
      information on certain variables and linkage to other health care databases. Most
      published studies to date have been in the area of drug safety. The General
      Practice Research Database has proved that valuable data can be collected in a
      general practice setting. The full potential of this rich computerized database
      has yet to come. This experience should serve to encourage others to develop
      similar population-based data in other countries.

PMID- 9643613
TI  - Pharmacovigilance in the pharmaceutical industry.

PMID- 9643614
TI  - Nitric oxide in the human cardiovascular system--SKB lecture 1997.

PMID- 9643615
TI  - Endothelin-1 induces vasodilation in human skin by nociceptor fibres and release
      of nitric oxide.
AB  - AIMS: Endothelin is a peptide produced by endothelial cells with many biological
      properties. In the human skin microcirculation endothelin induces neurogenic
      vasodilation associated with burning pruritus. We investigated the mechanisms
      involved in this response. METHODS: The effects of prolonged pretreatment with
      capsaicin, a specific inhibitor of polimodal nociceptor fibres, and of the nitric
      oxide synthase inhibitor L-NMMA on endothelin-1-induced vasodilation were studied
      in 15 human subjects. Furthermore, we investigated the effects of the ET(A)
      selective antagonist PD147953 on bradykinin-induced vasodilation. RESULTS: After
      local injection, endothelin-1 caused vasoconstriction at the injection site and a
      profound vasodilation in the surrounding area (flare reaction, P<0.01). This
      response was specific and not induced by saline, albumin, acetylcholine or an ET
      antagonist. Prolonged capsaicin pretreatment inhibited endothelin-1 induced
      vasodilation in the area surrounding the injection site, but not the central
      vasoconstriction at the injection site. Bradykinin also induced a marked
      vasodilation in the area surrounding the injection site; this was not inhibited
      by an ETA-selective antagonist, while the flare reaction was. L-NMMA applied at
      the site of the flare reaction prevented endothelin-1-induced vasodilation.
      CONCLUSIONS: Endothelin-1 in the human skin microcirculation stimulates polimodal
      nociceptor fibres leading to the release of nitric oxide. This response may play
      a pathophysiological role in inflammatory processes in the human skin.

PMID- 9643616
TI  - The influence of nifedipine and captopril on liver blood flow in healthy
      subjects.
AB  - AIMS: Application of single methods to assess liver blood flow (LBF) yielded
      conflicting results on the magnitude and duration of effect on LBF of oral
      nifedipine and captopril. The aim of this study was to investigate the influence
      of these drugs on LBF by simultaneous use of ICG infusion and echo-Doppler.
      METHODS: The study was performed according to a double-blind, placebo-controlled,
      randomized, cross-over design in nine healthy male volunteers. After an overnight
      fast and an equilibration period, subjects received a continuous i.v. indocyanine
      green (ICG) infusion for 4 h. At presumed ICG steady state (t=45 min), subjects
      were dosed with oral nifedipine (20 mg), captopril (50 mg) or placebo. During the
      experiment, blood sampling for ICG assay and measurement of portal venous blood
      flow (echo-Doppler) took place regularly. Treatments were compared using analysis
      of variance. Differences are reported with 95% confidence intervals (CI).
      RESULTS: The area under the curves (AUC) for ICG over 1 h and over 3 h after
      nifedipine were 15% (difference in AUC: + 0.6, + 7.0 mg l(-1) min) and 22% (+
      7.0, + 28.4 mg l(-1) min) lower compared with placebo. After captopril, the AUC
      values were 8-10% lower compared with placebo but the 95% CIs included zero.
      Portal venous flow was 15% (+ 5, + 86 ml min(-1)) higher compared to placebo
      after nifedipine but not after captopril (-3%; -49, +33 ml min(-1)). The duration
      of effect on liver blood flow lasted approximately 2 h but was variable (range:
      40-160 min). The time to maximal blood flow increase and the duration of effect
      after nifedipine were very similar for both measures of LBF. Changes in ICG
      concentrations could be reasonably well predicted from the changes in portal
      blood flow. CONCLUSIONS: Nifedipine increases LBF for a substantial period of
      time but the effect is variable between subjects. This effect could be detected
      by both the ICG method and echo-Doppler and the findings of both methods were in
      agreement. In this respect it is likely that captopril does not influence LBF in
      healthy volunteers as no effect was detected with either method.

PMID- 9643617
TI  - Distribution and excretion of sertraline and N-desmethylsertraline in human milk.
AB  - AIMS: To characterise milk/plasma (M/P) ratio and infant exposure, for sertraline
      and N-desmethylsertraline, in breast-feeding women taking sertraline for the
      treatment of depression. METHODS: Eight women (mean age 28 years) taking
      sertraline (1.05 mg kg(-1) day(-1)) and their infants (mean age 5.7 months) were
      studied. Sertraline and N-desmethylsertraline in plasma and milk were measured by
      high-performance liquid chromatography over a 24 h dose interval at steady-state.
      M/P values were estimated from area under the plasma and milk concentration-time
      curves. All milk produced was collected over the dose interval. Infant exposure
      was estimated as the product of actual or estimated milk production, and average
      drug concentration in milk, normalized to body weight and expressed as a
      percentage of the weight-adjusted maternal dose. RESULTS: Mean milk production
      was 321 ml day(-1) (range 34-974 ml). Mean M/P values of 1.93 and 1.64 were
      calculated for sertraline and N-desmethylsertraline respectively. Infant exposure
      estimated from actual milk produced was 0.2% and 0.3% of the weight-adjusted
      maternal dose for sertraline and N-desmethylsertraline (as sertraline
      equivalents) respectively. When calculated from estimated milk production (0.15 l
      kg(-1) day(-1)), infant exposure was significantly greater (P<0.0001) at 0.90%
      and 1.32% for sertraline and N-desmethylsertraline respectively. Neither
      sertraline nor its N-desmethyl metabolite could be detected in plasma samples
      from the four infants tested. No adverse effects were observed in any of the
      eight infants and all had achieved normal developmental milestones. CONCLUSIONS:
      Irrespective of the method of calculation of infant exposure, the mean total dose
      of sertraline and its N-desmethyl metabolite transmitted to infants via breast
      feeding is low and unlikely to cause any significant adverse effects.

PMID- 9643618
TI  - Distribution and excretion of venlafaxine and O-desmethylvenlafaxine in human
      milk.
AB  - AIMS: To characterise the transfer of venlafaxine (V) and its O-desmethyl
      metabolite (ODV) into human milk by measuring milk/plasma (M/P) ratio, and to
      estimate the likely dose received by a breast-fed infant. METHODS: Milk and
      plasma samples were collected from three lactating women who were taking
      venlafaxine for depression, and were at steady-state. In two of the patients,
      venous blood and milk samples were collected 0, 1, 2, 3, 4, 6, 8 and 12 h post
      dose, while in the third patient a single pair of blood and milk samples was
      obtained 0.83 h post dose. A plasma sample was obtained from each of their
      infants. V and ODV were measured in plasma and milk by high performance liquid
      chromatography. M/P was calculated and infant dose estimated as drug
      concentration in milk x a milk intake of 0.15 l kg(-1) day(-1), relative to the
      weight-adjusted maternal dose. RESULTS: Mean M/P for V was 4.1 (range 2.8-4.8)
      and 3.1 for ODV (range 2.8-3.8). The mean total infant dose (as V equivalents)
      was 7.6% (range 4.7-9.2%) of the maternal weight-adjusted dose, with
      approximately equal amounts of V (3.5%) and ODV (4.1%) in the dose. ODV (median
      100 microg I(-1)) was detected in the plasma of all three infants. The infants
      were healthy and showed no acute adverse effects. CONCLUSIONS: These preliminary
      data show that the total dose of V and ODV ingested by breast-fed infants can be
      as high as 9.2% of maternal intake. Moreover there were measurable concentrations
      of ODV in the infants' plasma. We recommend that exposed infants should be
      observed closely.

PMID- 9643619
TI  - Assessment of hepatic blood flow using continuous infusion of high clearance
      drugs.
AB  - AIMS: To provide methods for the translation of the concentration-time profile of
      highly cleared marker compounds into the underlying clearance and hepatic blood
      flow profile. METHODS: Continuous infusion of indocyanine green or sorbitol was
      used to assess the effect of the hepatic blood flow modifiers exercise,
      somatostatin and octreotide. Three distinct methods are described for the
      translation of concentration into flow: 1. assuming successive phases of constant
      clearance 2. point to point estimation of clearance using estimates of
      concentration change 3. using a parametric description of the flow profile in
      combination with the differential equations describing the change in marker
      concentrations. RESULTS: The marker compound concentration profiles are
      adequately described using the different methods. Exercise results in a decrease
      in hepatic blood flow of about 80%. Somatostatin and octreotide elicit an
      indistinguishable hepatic blood flow decrease from 1.49 to 1.07 l min(-1). Return
      to baseline takes much longer for octreotide (half-life 126+/-104 min) than for
      somatostatin (half-life 4.29+/-3.55 min). CONCLUSIONS: Translation of
      concentration profiles into clearance profiles is possible making continuous
      assessment of hepatic blood flow feasible.

PMID- 9643620
TI  - Pharmacokinetics of bambuterol in healthy subjects.
AB  - AIMS: To study the pharmacokinetics and bioavailability of the prodrug bambuterol
      and its bronchodilator moiety terbutaline in healthy subjects. METHODS: Eight
      healthy subjects (four women) received intravenous doses of bambuterol and
      terbutaline. On a third occasion, they, plus another four subjects, ingested oral
      bambuterol as a single dose followed by repeated doses once daily for 7 days.
      Plasma concentrations and urinary excretion of bambuterol and terbutaline were
      measured. RESULTS: After intravenous administration, renal clearances of
      bambuterol and terbutaline were similar (about 140 ml min(-1)), but there was a
      five-fold difference in total clearance (bambuterol 1.25 l min(-1), terbutaline
      0.23 l min(-1)). Volume of distribution (Vss) was 1.6 l kg(-1) b.w. for both
      substances. A similar renal clearance of bambuterol was found during oral
      administration but that of terbutaline decreased (to about 120 ml min(-1)). Mean
      terminal half-life of bambuterol was 2.6 h after intravenous and 12 h after oral
      administration, implying that uptake was rate-limiting. Mean residence time of
      terbutaline generated from oral bambuterol was 34 h compared with 8.0 h when
      terbutaline as such was infused. Generated terbutaline had a bioavailability of
      36% (28-46) after intravenous and 10.2% (6.1-13.2) after oral administration of
      the prodrug. Bambuterol was well tolerated. The mean activity of plasma
      cholinesterase, an enzyme catalyzing bambuterol metabolism, was inhibited between
      30-60% during repeated oral dosing. It virtually regained original activity
      within 48 h after the last dose. CONCLUSIONS: The plasma concentration
      ofterbutaline fluctuated little during repeated oral administration (mean peak:
      trough ratio 1.9), as a result of prolonged absorption of bambuterol and slow
      formation of terbutaline. Thus, the pharmacokinetic properties of bambuterol make
      it suitable for oral once-daily dosage.

PMID- 9643621
TI  - Pharmacokinetics of bambuterol in subjects homozygous for the atypical gene for
      plasma cholinesterase.
AB  - AIMS: It has been assumed that both plasma cholinesterase (EC 3.1.1.8) and
      oxidative enzymes are needed for optimum formation of the bronchodilator
      terbutaline from its biscarbamate prodrug bambuterol. The present study aimed at
      investigating the fate of bambuterol in subjects with deficient plasma
      cholinesterase but with normal oxidative (CYP2D6) capability. METHODS: The
      pharmacokinetics of bambuterol and terbutaline were studied in four healthy
      subjects (two men and two women) being homozygous for the atypical gene for
      plasma cholinesterase. Their oxidative metabolism was apparently good as they
      were all rapid metabolizers of debrisoquine. Bambuterol hydrochloride 20 mg was
      given orally once daily for 10 days, and plasma and urine samples were taken for
      1.5 days (plasma) and 4.5 days (urine) after administration of the last dose.
      RESULTS: The pharmacokinetic parameters in the present study were grossly similar
      to those found in a study of bambuterol in subjects with normal plasma
      cholinesterase activity (N). However, subjects with atypical cholinesterase had a
      shorter terminal half-life of bambuterol (a measure of uptake rate), 4.8-12.6 h
      vs 8.3-22.3 h in N, and slightly higher plasma concentrations of bambuterol
      (average concentrations 1.9-3.7 nmol l(-1) vs 1.5-3.1 nmol l(-1) in N).
      Peak/trough terbutaline plasma concentrations ratios (2.1-3.2) were somewhat
      increased, but average plasma concentrations (8.3-14.5 nmol l(-1)) and terminal
      half-life (16.5-21.8 h) of terbutaline did not differ. CONCLUSIONS: In Caucasian
      populations, one subject out of 2500 is homozygous for the atypical gene for
      plasma cholinesterase. The atypical enzyme has a much lower affinity for
      bambuterol than the normal enzyme. Nevertheless, the subjects with atypical
      cholinesterase were able to produce terbutaline as efficiently as normal
      subjects. This might be explained by an altered uptake and metabolism in the
      absence of plasma cholinesterase, or the importance of this enzyme for the
      formation of terbutaline from bambuterol in vivo may have been overestimated.

PMID- 9643622
TI  - Absorption kinetics of oral sotalol combined with cisapride and sublingual
      sotalol in healthy subjects.
AB  - AIMS: To study the absorption kinetics of sotalol following administration of
      different formulations. A formulation which results in fast absorption might be
      useful in the episodic treatment of paroxysmal supraventricular tachycardia
      (SVT), atrial fibrillation (Afib) or atrial flutter (Afl). METHODS: In an open
      randomized crossover study seven healthy male volunteers were given an
      intravenous infusion of 20 mg sotalol, for assessing the absolute
      bioavailability, an oral solution containing 80 mg sotalol, an oral solution
      containing both 80 mg sotalol and 20 mg cisapride and an 80 mg sotalol tablet,
      which was taken sublingually. RESULTS: The addition of cisapride decreased the
      time at which maximum serum concentrations were reached (tmax) from 2.79 (1.85
      4.34) h to 1.16 (0.68-2.30) h (P=0.009) [95% CI: -2.59, -0.55] and increased the
      absorption rate constant (ka) from 0.49 (0.31-0.69) h(-1) to 1.26 (0.52-5.61) h(
      1) (P=0.017). The absolute bioavailability of sotalol was reduced by cisapride
      from 1.00+/-0.15 to 0.70+/-0.26 (P=0.006), while maximum serum concentrations of
      both oral solutions were not significantly different. Compared with the
      sublingually administered tablet with a median tmax of 2.12 (0.89-3.28) h, the
      sotalol/cisapride oral solution gave a smaller tmax (p=0.009) [95% CI: -1.64, 
      0.36]. The ka of the sotalol/cisapride solution was significantly (P=0.010)
      larger than the ka of 0.56 (0.33-0.75) h(-1) found after sublingual
      administration of the tablet. CONCLUSIONS: The sotalol/cisapride oral solution
      might be suitable for the episodic treatment of SVT, Afib or Afl.

PMID- 9643623
TI  - Verapamil SR and trandolapril combination therapy in hypertension--a clinical
      trial of factorial design. German Hypertension Study Group.
AB  - AIMS: To investigate the dose-response relationship and contribution of verapamil
      SR and trandolapril given in combination once a day for the treatment of
      essential hypertension. METHODS: A randomized, double-blind, placebo controlled,
      factorial, 12 arm parallel group comparison with placebo, verapamil SR (120, 180
      mg), trandolapril (0.5, 1.0, 2.0 mg) covering all combinations of both drugs. A 4
      week placebo run-in period followed by 6 weeks of treatment. Four hundred and
      fifty-six patients from office practice (22 centres) with mild to moderate
      hypertension enrolled and 426 with diastolic pressure > or = 100 mm Hg at the end
      of run-in period were randomized. Main outcome measures were reduction in sitting
      systolic (SBP) and sitting diastolic (DBP) blood pressure. RESULTS: The
      combination of verapamil SR and trandolapril, particularly verapamil SR 180 mg
      and trandolapril 0.5 or 1.0 mg was significantly superior to both monocomponents
      at the same dose (P<0.05). For these combinations, the adjusted mean reductions
      in DBP from baseline to last visit were 14.1 and 16.0 mm Hg, respectively.
      Response surface analysis provided further evidence that these combinations were
      optimal for antihypertensive efficacy. All treatments were well tolerated. The
      incidence of adverse events did not differ significantly between treatment
      groups; the profile of adverse events on combination therapy was mild and
      consistent with that of each monocomponent. CONCLUSIONS: All dosage combinations
      of verapamil SR and trandolapril produced significantly greater reduction of
      blood pressure than the monotherapy at the same dosage. However, verapamil SR 180
      mg in combination with trandolapril 1.0 mg was the dosage with the greatest blood
      pressure reduction and had the greatest effects compared with the monocomponents.

PMID- 9643624
TI  - Different standards for reporting ADRs to herbal remedies and conventional OTC
      medicines: face-to-face interviews with 515 users of herbal remedies.
AB  - AIMS: To determine whether adverse drug reactions (ADRs) to herbal remedies would
      be reported differently from similar ADRs to conventional over-the-counter (OTC)
      medicines by herbal-remedy users. METHODS: Face-to-face interviews (using a
      structured questionnaire) with 515 users of herbal remedies were conducted in six
      pharmacy stores and six healthfood stores in the UK. The questionnaire focused on
      the likely course of action taken by herbal-remedy users after experiencing an
      ADR associated with a conventional OTC medicine and a herbal remedy. RESULTS:
      Following a 'serious' suspected ADR, 156 respondents (30.3%) would consult their
      GP irrespective of whether the ADR was associated with the use of a herbal remedy
      or a conventional OTC medicine, whereas 221 respondents (42.9%) would not consult
      their GP for a serious ADR associated with either type of preparation. One
      hundred and thirty-four respondents (26.0%) would consult their GP for a serious
      ADR to a conventional OTC medicine, but not for a similar ADR to a herbal remedy,
      whereas four respondents (0.8%) would consult their GP for a serious ADR to a
      herbal remedy, but not for a similar ADR to a conventional OTC medicine. Similar
      differences were found in attitudes towards reporting 'minor' suspected ADRs.
      CONCLUSIONS: Consumers of herbal remedies would act differently with regard to
      reporting an ADR (serious or minor) to their GP depending on whether it was
      associated with a herbal remedy or a conventional OTC medicine. This has
      implications for herbal pharmacovigilance, particularly given the increasing use
      of OTC herbal remedies. The finding that a high proportion of respondents would
      not consult their GP or pharmacist following ADRs to conventional OTC medicines
      is also of concern.

PMID- 9643625
TI  - Variability in trough plasma saquinavir concentrations in HIV patients--a case
      for therapeutic drug monitoring.

PMID- 9643626
TI  - Peptide siderophores.
AB  - Siderophores are low molecular weight iron chelators, produced by virtually all
      bacteria, fungi and some plants. They serve to deliver the essential element
      iron, barely soluble under aerobic conditions, into microbial cells. Siderophores
      are therefore important secondary metabolites which are very often based on amino
      acids and their derivatives. Biosynthesis, transport, regulation and chemical
      synthesis of natural siderophores and their analogues is of considerable interest
      for the protein and peptide chemist. This review gives an overview of the
      structural classes of peptidic siderophores, along with data on their
      biosynthesis. On a number of representative examples, strategies and schemes of
      their chemical synthesis are described.

PMID- 9643627
TI  - Presentation of antigenic peptides by products of the major histocompatibility
      complex.
AB  - Molecules encoded by the major histocompatibility complex (MHC) are polymorphic
      integral membrane proteins adapted to the presentation of peptide fragments of
      foreign antigens to antigen-specific T-cells. The diversity of infectious agents
      to which an immune response must be mounted poses a unique problem for receptor
      ligand interactions; how can proteins whose polymorphism is necessarily limited
      bind an array of peptides almost infinite in its complexity? Both MHC class I and
      class II determinants have achieved this goal by harnessing a limited number of
      peptide side chains to anchor the epitope in place while exploiting conserved
      features of peptide structure, independent of their primary sequence. While class
      I molecules interact predominantly with the N- and C-termini of peptides, class
      II determinants form an extensive hydrogen bonding network along the length of
      the peptide backbone. Such a strategy ensures high-affinity binding, while
      selectively exposing the unique features of each ligand for recognition by the T
      cell receptor.

PMID- 9643628
TI  - PEGA supports for combinatorial peptide synthesis and solid-phase enzymatic
      library assays.
AB  - Permeable resins cross-linked with long PEG chains were synthesized for use in
      solid-phase enzyme library assays. High molecular weight bis-amino-polyethylene
      glycol (PEG) 4000, 6000, 8000 were synthesized by a three-step reaction starting
      from PEG-bis-OH. Macromonomers were synthesized by partial or di-acryloylation of
      bis-amino-PEG derivatives. Bis/mono-acrylamido-PEG were copolymerized along with
      acrylamide by inverse suspension copolymerization to yield a less cross-linked
      resin (Type I, compounds 6-9). Furthermore, acryloyl-sarcosin ethyl ester was co
      polymerized along with bis-acrylamido PEG to obtain more crosslinked capacity
      resin (Type II, compounds 13-19). N,N-Dimethylacrylamide was used as a co-monomer
      in some cases. The polymer was usually obtained in a well-defined beaded form and
      was easy to handle under both wet and dry conditions. The supports showed good
      mechanical properties and were characterized by studying the swelling properties,
      size distribution of beads, and by estimating the amino group capacity. Depending
      on the PEG chain length, the monomer composition and the degree of cross-linking
      the PEGA supports showed a high degree of swelling in a broad range of solvents,
      including water, dichloromethane, DMF, acetonitril, THF and toluene: no swelling
      was observed in diethyl ether. The PEGA resins (Type I) with an amino acid group
      capacity between 0.07 and 1.0 mmol/g could be obtained by variation of the
      monomer composition in the polymerization mixture. Fluorescent quenched peptide
      libraries were synthesized on the new polymer using a multiple column library
      synthesizer and incubated with the matrix metalloproteinase MMP-9 after it had
      been activated by 4-aminophenyl mercuric acetate resulting in 67/83 kDa active
      enzyme. The bright beads were separated manually under a fluorescence microscope
      and sequenced to obtain peptide substrates for MMP-9. After treatment with
      ethylene diamine, high-loaded resins (Type II) have been employed in continuous
      flow peptide synthesis to yield peptides in excellent yield and purity.

PMID- 9643629
TI  - Peptides from bovine brain: structure and biological role.
AB  - Fractionation of bovine brain extracts followed by automatic Edman sequencing of
      individual components resulted in identification of 107 endogenous peptides
      formed from functional proteins (haemoglobin, myelin basic protein, cytochrome c
      oxidase, etc) or unknown precursors. Several of the newly identified brain
      peptides demonstrate different types of biological activity; some of the
      substances show considerable overlap with the known biologically active peptides.
      It is suggested that these peptides should participate in regulation of
      extracellular and intracellular biochemical processes. A concept of 'tissue
      specific peptide pool' is formulated describing a novel system of peptidergic
      regulation, complementary to the conventional hormonal and neuromodulatory
      systems. According to that description functional proteins provide their
      proteolytically derived fragments for maintaining the tissue homeostasis by
      modulating the availability of peptide receptors to respective 'true' ligands.

PMID- 9643630
TI  - Maternal serum uric acid levels in preeclamptic twin pregnancies.

PMID- 9643631
TI  - Obstetrical factors governing the etiopathogenesis of lambdoid synostosis.
AB  - Lambdoid synostosis results in skull deformities of varying degrees characterized
      by occipital flattening over the involved suture and other compensatory changes
      in skull shape. Such changes include contralateral occipital bossing,
      contralateral frontal flattening, ipsilateral frontal bossing, and ipsilateral
      anteroinferior displacement of the pinna (ear shearing). These deformities tend
      to worsen during the first year of life. The etiology has been attributed to
      genetic factors and primary disorders of bone growth, in addition to secondary
      effects of other diseases and modulators of the in utero environment. To
      determine causal factors in the development of lambdoid synostosis, the authors
      reviewed medical records of the mothers of 13 children with lambdoid synostosis
      who were treated at the University Medical Center of the State University of New
      York at Stony Brook. Pre- and perinatal events, prior obstetrical, gynecological,
      medical, social, and family histories were considered. Births of normal infants
      immediately prior to and just after the affected babies were born were selected
      as controls. There is a significant association between increased duration of the
      first stage of labor and the development of lambdoid synostosis. Furthermore, our
      results indicate that this condition has a predilection toward male infants, and
      may be associated with preterm labor.

PMID- 9643632
TI  - Undetected breech presentation: impact on external version and cesarean rates.
AB  - The objective of this study was to determine the impact of undetected breech
      presentation on an external cephalic version program. We performed a
      retrospective analysis of all external cephalic versions attempted over a 1-year
      interval. We then analyzed all cesarean operations performed for the indication
      of breech presentation over the same interval. Cases involving twin gestations
      and premature births were excluded. We found that 21% of term breech
      presentations were not detected before the onset of labor and an additional 15%
      were not detected until after 38 weeks' gestation. Increased third-trimester
      screening for breech presentation could potentially decrease the need for
      cesarean delivery.

PMID- 9643633
TI  - Significance of sporadic deceleration during antepartum testing in term
      pregnancies.
AB  - We have investigated the significance of single sporadic deceleration during
      reactive nonstress testing in normal pregnancies at term. A prospective study was
      performed during a 1-year period including 4742 nonstress tests performed between
      the 38th and 42nd weeks of pregnancy in patients referred to our department for
      antepartum testing and without any complication or pathology. Nonstress test
      (NST) was carried out with the patient lying on her left side, and was defined as
      reactive if at least two accelerations of 15 beats/min (bpm) or more lasting 15
      sec were observed in a 20-min period. Sporadic deceleration was defined as a
      decrease in the fetal heart rate to less than 90 bpm or a decrease of 40 bpm
      below the baseline, lasting at least 2 min. The sporadic deceleration was
      considered as single when only one appeared in the first 20 min of monitoring and
      repeated when observed again once in at least one subsequent monitoring. Thirty
      four cases of single sporadic deceleration were observed among women with
      reactive NST. In 14 cases there were repeated sporadic decelerations. The
      patients were divided into two groups according to the presence or absence of
      repeated decelerations. Outcomes of patients with repeated sporadic decelerations
      were compared with a group of 34 patients where sporadic decelerations were not
      observed during the antepartum testing. A significantly higher percentage of
      pathological fetal heart rate traces during labor were observed in the group of
      repeated decelerations. In conclusion the presence of repeated sporadic
      decelerations during a reactive NST suggests that the cause of cord compromise is
      persistent and recurrent cord compression is possible. Therefore, in these cases
      an increased fetal risk could be expected.

PMID- 9643634
TI  - Successful fetal outcome after exposure to idarubicin and cytosine-arabinoside
      during the second trimester of pregnancy--a case report.
AB  - Chemotherapeutic agents administered to the mother during pregnancy may severely
      jeopardize the fetus. We describe a newborn girl who had been exposed to
      idarubicin and cytosine-arabinoside during the second and third trimesters of
      pregnancy due to treatment of newly diagnosed acute myeloid leukemia in the
      mother. The child had no structural congenital abnormalities. Adverse effects
      observed were prematurity, growth retardation, mildly disturbed transaminases and
      erythroblastosis, all of which were self-limiting with no permanent sequelae.

PMID- 9643635
TI  - Supernumerary umbilical vein resulting in a four-vessel umbilical cord.
AB  - The birth of an infant with increased number of umbilical veins is a rare event
      and has been previously reported to be associated with a high incidence of major
      congenital anomalies. This report documents a normal infant with two umbilical
      veins resulting in a four vessel cord. A male infant (third of triplet pregnancy
      resulting from multiple zygote implantation) was born at 30 weeks' gestation
      weighing 1320 g.Two umbilical veins and two umbilical arteries were noted on
      cannulation and X ray. Physical examination and cranial, abdominal, and cardiac
      ultrasound exam were normal. One-year follow-up was normal. The birth of infant
      with a four-vessel cord mandates comprehensive workup for associated anomalies
      but this case indicates that such a finding is not always ominous.

PMID- 9643636
TI  - Pregnancy and tuberculosis: influence of treatment on perinatal outcome.
AB  - The objective of this article is to evaluate the impact of tuberculosis (TB) on
      perinatal outcome in a cohort of 25 pregnant women with TB treated at the
      National Institute of Perinatology (Mexico, City) from March 1990 to September
      1995. They were compared with a cohort of normal pregnant women; both cohorts
      were matched by age, gestational age, and socioeconomic status. For purposes of
      analysis, patients with TB were further stratified into two groups: one included
      9 women who started treatment either before or at the beginning of pregnancy, and
      the other constituted 16 women who started treatment in either the second or
      third trimester of gestation. Thirteen women (52%) had pulmonary TB, 7 (28%) had
      renal infection, and the rest of patients had diverse extrapulmonary localization
      of the infection. Obstetrical morbidity and neonatal mortality were significantly
      higher in pregnant women with TB who started treatment late in pregnancy.
      Perinatal morbidity was similar in pregnant women receiving antituberculous drugs
      early during pregnancy to that in uninfected women. We conclude that TB
      represents a risk factor for pregnancy. Early treatment of the disease during
      gestation reverts its negative impact on perinatal outcome.

PMID- 9643637
TI  - Recurrent chlamydial colonization during pregnancy.
AB  - To evaluate the prevalence of and associated factors for recurrent Chlamydia
      trachomatis infection in pregnant women, a retrospective cohort study was
      conducted in an urban prenatal clinic in an underserved area. Women with
      chlamydial carriage in pregnancy between 1992 and 1996 were identified by a
      direct DNA assay. Entrance criteria limited the population to those who were
      positive for chlamydia, were treated, had proof of cure and had at least one
      subsequent test for chlamydia, all in the same pregnancy. Of the 149 women who
      met entrance criteria, 25 (17%) had recurrent chlamydial carriage. The only
      identified risk factor was maternal age <20 years (21 of 98 vs. 4 of 51, odds
      ratio = 3.21). Infection with gonorrhea or other sexually transmitted diseases
      during the same pregnancy were not predictive of reinfection. Initial therapy
      with azithromycin, when compared to erythromycin, did not appear protective for
      recurrent infection. Pregnant adolescents are more likely to have recurrent
      chlamydial infection. Prenatal care programs should consider this when counseling
      and treating these patients.

PMID- 9643638
TI  - Gaucher's disease and pregnancy.
AB  - Gaucher's disease is an autosomal recessive lysosomal storage disease, resulting
      from a deficiency of the enzyme glucocerebrosidase, which is required for the
      lysosomal degradation of glycolipids. The clinical manifestations of the disease
      show a large heterogeneity, including hepatosplenomegaly, "bone crisis" and
      fracture, anemia, thrombocytopenia and, in the rarest types II and III,
      neurological decompensation. Type I, the most common form, usually presents with
      less severe symptoms and at a more advanced age. More than 30 mutations within
      the glucocerebrosidase gene have been recognized, and certain mutations seem to
      be related with a particular phenotype expression of the disease. Modern
      diagnosis of Gaucher's disease is performed by either determining the enzyme
      activity in peripheral blood leukocytes or through DNA-based analysis. Pregnancy
      concurrent with Gaucher's disease has several risks, including an increased
      severity of anemia and thrombocytopenia that can potentiate postpartum bleeding,
      and increased risk of infection and possibly an increased spontaneous abortion
      rate. Nevertheless, the majority of these pregnancies seem to proceed to term
      without significant complications. The effects that pregnancy might have on the
      course of the disease are still unresolved. Enzyme replacement therapy with
      alglucerase is the treatment of choice for patients with Gaucher's disease, but
      it is yet to be shown whether alglucerase reduces the risk of these complications
      during pregnancy and whether its use has any adverse effect on fetal development.
      We present an extensive review of the current literature regarding Gaucher's
      disease with special emphasis on pregnancies coexistent with this disease and, an
      analysis of the genetics, relevant prenatal diagnostic issues, and current
      treatment modalities.

PMID- 9643639
TI  - Prenatal ultrasonographic diagnosis of fetal intracranial tumors: a review.
AB  - Our objective was to review current literature pertaining to prenatal
      ultrasonography of various fetal intracranial neoplastic and non-neoplastic
      tumors. To this goal, all manuscripts published in the English language regarding
      this topic obtained from a MEDLINE search from 1966 through January 1998 were
      selected and reviewed. Additional sources were identified through cross
      referencing. Intracranial fetal tumors are extremely rare and precise diagnosis
      is dependent on histology examination of tissue obtained at subsequent surgery or
      autopsy. Currently, prenatal ultrasonographic findings associated with the
      following fetal intracranial tumors have been described: teratomas;
      neuroepithelial tumors including: glioblastoma, astrocytoma, gangliocytoma,
      medulloblastoma, choroid plexus, and papilloma; and mesenchymal tumors. Non
      neoplastic fetal intracranial tumors are even less frequent and include:
      unilateral megalencephaly, heterotopia, and lipoma of the corpus callosum.
      Cardinal ultrasonographic findings associated with fetal intracranial tumors
      include: echogenic and semicystic space occupying lesions with or without
      distortion of normal symmetrical intracranial (usually midline) structures,
      calcifications, craniomegaly, polyhydramnios, obstructive hydrocephaly, high
      output cardiac failure (hydrops fetalis), the presence of other associated
      structural anomalies, and infrequently abnormal cerebral Doppler flow
      velocimetry.

PMID- 9643640
TI  - Development of pulmonary lipophilic antioxidants and peroxidizable lipids during
      lung maturation.
AB  - The objective of this article is to test whether the concentration of potentially
      oxidizable lipids (polyunsaturated fatty acids [PUFA], total and free
      cholesterol) and lipophilic antioxidants (plasmalogens, vitamin E) in the fetal
      lung correlate with lung maturation (P/S ratio). In amniotic fluid
      palmitic/stearic acid (P/S) ratio, concentrations of PUFA, total and free
      cholesterol, vitamin E, and plasmalogens were measured. Ratio of PUFA to stearic
      acid (PUFA/S ratio) was determined in lung effluent of 15 preterm infants with
      IRDS and compared with values from 15 term healthy infants. Concentrations of
      plasmalogens, PUFA, total and free cholesterol increase significantly with
      increasing P/S ratio. No correlation of vitamin E with lung maturation has been
      found. The PUFA/S ratio is significantly lower in lung effluent of preterm (0.79
      +/- 0.27) when compared with term infants (2.02 +/- 0.38). Our results suggest
      that the higher susceptibility of preterm infants for oxidative lung injury is
      not caused by an unfavorable ratio of oxidizable lipids to lipophilic
      antioxidants in surfactant, but rather by a lower amount of PUFA containing
      surfactant lipids. Our results are in accordance with data from Sosenko et al.
      who have shown that high levels of PUFA in the rat lung have a protective effect
      against oxygen-induced lung damage.

PMID- 9643641
TI  - Uncomplicated baseline fetal tachycardia or bradycardia in postterm pregnancies
      and perinatal outcome.
AB  - OBJECTIVE: to assess perinatal outcome in post-term pregnancies in which fetal
      heart rate (FHR) monitoring revealed either uncomplicated baseline fetal
      tachycardia (> or = 160 bpm) or fetal bradycardia (< or = 120 bpm). STUDY DESIGN:
      We performed a case-control study of patients who underwent fetal assessment
      between July 1989 and June 1995, as part of post-term evaluation. Inclusion
      criteria consisted of nonlaboring afebrile patients with singleton post-term
      pregnancies > or = 41 weeks of gestation by strict dating criteria (last
      menstrual period consistent with ultrasound biometric parameters obtained prior
      to 20 weeks' gestation), normal fetal anatomy, intact membranes, and reactive
      nonstress test with no evidence of chorioamnionitis. Patients with fetal tachy or
      brady arrhythmias, FHR decelerations, or loss of short-term beat-to-beat
      variability were excluded. Baseline FHR was recorded retrospectively by an
      observer blinded to maternal and neonatal clinical outcome. For each case of
      uncomplicated baseline fetal tachycardia (> or = 160 bpm) or bradycardia (< or =
      120 bpm), either two or three control cases (matched for maternal age and
      parity), with FHR > 120 bpm and < 160 bpm, were identified. Outcome variables
      assessed included: incidence of cesarean delivery, nuchal cord at delivery,
      meconium-stained amniotic fluid (AF), 5-min Apgar score < 7, fetal growth
      restriction (< 10th percentile for 41 weeks' gestation), meconium aspiration
      syndrome, and neonatal intensive care unit (NICU) admission. Statistical analysis
      included two-tailed t-test and chi2 test when appropriate, with p < 0.05
      considered significant throughout. RESULTS: During the study period 1390 post
      term patients (6.81% of the general population) were assessed. Of these, 31
      (2.23%) fetuses exhibited baseline FHR > or = 160 bpm, and 76 fetuses (5.46%)
      exhibited baseline FHR < or = 120 bpm. No significant differences were noted in
      the incidence of cesarean delivery, presence of nuchal cord at delivery, meconium
      stained AF, 5-min Apgar scores < 7, fetal growth restriction, meconium aspiration
      syndrome, or the incidence of NICU admissions between the groups of patients with
      fetal tachycardia, bradycardia, and their respective controls. CONCLUSIONS:
      Uncomplicated baseline fetal tachycardia or bradycardia in postterm patients are
      not associated with an increase in the incidence of adverse perinatal outcome.

PMID- 9643642
TI  - Prenatal diagnosis by chorionic villus sampling in multiple pregnancies prior to
      fetal reduction.
AB  - Ovulation induction and assisted-reproduction techniques have dramatically
      increased the incidence of high-risk multiple pregnancies over the past 10 years.
      Perinatal outcome may be improved by the use of multifetal reduction. The fetus
      to be reduced used to be selected only on technical grounds. We report on the
      results of prenatal diagnosis by chorionic villus sampling (CVS) during the first
      trimester in 32 multifetal pregnancies in which fetal reduction was requested.
      The mean gestational age at CVS was 10.5 weeks. Chromosomal analyses were
      available for all sampled fetuses, three of which were chromosomally abnormal. In
      24 couples, fetal reduction to twin pregnancies was successfully carried out
      within 1 week after the CVS. In seven cases, the couples elected not to proceed
      with fetal reduction after receiving information that the chromosomal analysis
      was normal in all fetuses. Mean gestational ages at delivery were, respectively,
      34.6 and 31.8 weeks in the reduced and the nonreduced groups (p = 0.04). No fetal
      losses occurred in either group; one neonatal death was observed after a preterm
      delivery because of preeclampsia in a twin pregnancy. Prenatal cytogenetic
      diagnosis during the first trimester in multiple pregnancies prior to fetal
      reduction appears to be feasible, accurate, and safe. Abnormal chromosomal
      results indicate the fetus(es) to be reduced. The parents' decisions not to
      proceed with the fetal reduction procedure, where chromosomal results in all the
      fetuses were normal, were unexpected.

PMID- 9643643
TI  - Temporal expression of elastic fiber components in bladder development.
AB  - Fetal and postnatal bovine bladders were examined for expression of elastic fiber
      components by immunohistochemistry as well as by measurement of steady state mRNA
      levels. Expression of fibrillin-1, microfibril-associated glycoprotein (MAGP) and
      elastin during the fetal period were compared with that of postnatal two year old
      animals (heifers) and adults. Each bladder was separated into two distinct tissue
      samples: 1) the outer smooth muscle layer (detrusor) and 2) the inner epithelium
      (urothelium) lined lamina propria (urotherial-lamina propria). Each of these
      samples was analyzed separately. Distribution of the elastic fiber components,
      determined by immunohistochemistry with matrix-specific antibodies, was different
      depending upon the region of the bladder wall examined and its developmental
      stage. In particular, MAGP and fibrillin-1 were conspicuously present in the
      urothelium during the later fetal stages. RNA products of elastic fiber genes
      were detectable both in the detrusor smooth muscle and urothelial-lamina propria
      fractions. The highest level of expression occurred in the urothelial-lamina
      propria fraction during the late second-early third trimester. Elastin expression
      was different from that of MAGP and fibrillin-1. The highest levels of steady
      state elastin mRNA occurred at the earliest developmental stages examined and
      then progressively decreased through term. A high level of elastin expression
      occurred within the inner or lamina propria layer of the bladder. Since this
      layer is the functional capacitance layer within the bladder, its flexibility is
      likely related to the structural integration of elastin and associated
      microfibrillar components.

PMID- 9643644
TI  - The modification of alveolar bone proteoglycans by reactive oxygen species in
      vitro.
AB  - Reactive oxygen species (ROS) are being increasingly implicated in the connective
      tissue degradation associated with chronic inflammatory conditions, such as
      periodontal disease. The present study investigated the effects of ROS on the
      proteoglycans (PG) of alveolar bone which are important structural components
      within the periodontium. PG were isolated from ovine alveolar bone and exposed to
      increasing concentrations of hydrogen peroxide (H2O2) or to a hydroxyl radical
      (.OH) flux for 1 h or 24 h, and the degradation products examined for
      depolymerisation and chemical modification of the PG structure. ROS were
      demonstrated to be capable of degrading alveolar bone PG in vitro, the .OH
      species resulting in greater modification than H2O2. The degradative effects
      observed included cleavage of the protein core and depolymerisation of the GAG
      chains. The core proteins were more susceptible to degradation than the GAG
      chains in the presence of H2O2 alone, although both the core proteins and the GAG
      chains were extensively degraded in the presence of a .OH flux for both 1 h and
      24 h. Exposure of the PG to .OH for 24 h resulted in significant modification to
      the amino acid composition with decreases in the proportion of leucine and the
      complete loss of proline, tyrosine and phenylalanine evident. The results
      highlight the potential role of ROS as an important mechanism in considering the
      pathology of periodontal tissue destruction.

PMID- 9643645
TI  - TGF-beta1 binding protein-like modules of fibrillin-1 and -2 mediate integrin
      dependent cell adhesion.
AB  - Human fibrillin, a major component of the extracellular matrix, exists as two
      highly homologous forms (fibrillin-1 and -2). Several modules of fibrillin are
      homologous to TGF-beta1 binding protein. Two of these modules, D25 (the 25th
      module of fibrillin-1 and -2 D segment) and D12 (the 12th module of fibrillin-2 D
      segment) contain the cell adhesion motif arginyl-glycyl-aspartyl (RGD). The
      ability of RGD to mediate adhesion to D25-1 and D12-2 was investigated using
      bacterially expressed fusion proteins. Human skin fibroblasts and murine L-cells
      were used in microassays of cell attachment and cell spreading on fibrillin
      fusion-protein substrata. Dose-dependent experiments and competitive inhibition
      by soluble RGD-containing peptides demonstrated that D25-1 and D12-2 mediate RGD
      dependent cell adhesion. These results provide evidence for a cell adhesion
      function of fibrillin-2. Inhibition with anti-integrin antibodies showed that
      alpha(v) and beta3 integrins mediate adhesion to D25-1, while alpha3, alpha(v)
      and beta1 are involved in adhesion to D12-2. Binding of different receptors may
      elicit distinct cell signalling supporting the hypothesis that fibrillin-1 and
      fibrillin-2 have distinct roles.

PMID- 9643646
TI  - Tubulointerstitial nephritis antigen (TIN-ag) is expressed in distinct segments
      of the developing human nephron.
AB  - Tubulointerstitial nephritis antigen (TIN-ag) is a 58 kDa glycoprotein restricted
      within the kidney to basement membranes underlying the epithelium of Bowman's
      capsule and proximal and distal tubules. Autoantibody formation against this
      component has been described in association with primary immune-mediated
      tubulointerstital nephritis, membranous nephropathy and anti-glomerular basement
      membrane nephritis. In the present report, the ontogeny of this protein was
      studied in human fetal kidney tissue by immunohistochemical analysis of immature
      and developing nephrons using a panel of monoclonal and polyclonal antibodies.
      TIN-ag is first detected in basement membranes underlying the epithelium of
      Bowman's capsule of early capillary loop stage glomeruli and the primitive
      proximal tubule. No detectable expression is observed in the basement membranes
      of the branching ureteric bud, nephrogenic vesicle, or comma shape and s-shape
      stages of nephrogenic development. Increased staining of the proximal tubular
      basement membrane is associated with outgrowth of the primitive tubule from the
      urinary pole of the developing glomerulus. In more mature fetal tubules, TIN-ag
      expression closely resembles that of previously reported observations in mature
      tissue where it is present in high amounts in the basement membranes of proximal
      tubules, and to a lesser extent in Bowman's capsule and distal tubules. Our
      results suggest that TIN-ag expression is developmentally regulated in a precise
      spatial and temporal pattern throughout nephrogenesis.

PMID- 9643647
TI  - Reduction in basic fibroblast growth factor mediated angiogenesis in vivo by
      linomide.
AB  - Linomide (N-phenylmethyl-1,2-dihydro-4-hydroxyl-1-methyl-2-oxoquinoline-3-carboxa
      mide) is a novel immunomodulator with a potent anti-tumoral activity. This study
      was undertaken to test the effect of Linomide on basic fibroblast growth factor
      (bFGF) induced angiogenesis in vivo, which manifests itself in an increased
      number of blood vessels per unit of cell infiltrated area. Subcutaneously
      implanted polyvinyl alcohol sponges (PVS) in guinea pigs were used as a model
      system to quantitate angiogenesis in vivo. Oral treatment with Linomide was able
      to reduce significantly the bFGF induced blood vessel growth and proliferation
      within the implanted PVS, relative to untreated controls. In addition, Linomide
      significantly reduced the bFGF mediated augmentation of protein and collagen
      content in the implanted PVS, indicating an inhibition in the deposition of
      extracellular matrix (ECM). We conclude that the potent inhibition of bFGF
      induced angiogenesis by Linomide in vivo in addition to immunomodulatory effects
      may have potentially important clinical applications.

PMID- 9643648
TI  - The influence of inflammation-mediated osteopenia (IMO) on the structure of
      rabbit bone and skin collagen fibrils.
AB  - The influence of Inflammation Mediated Osteopenia (IMO) on rabbit skin and bone
      (trabecular and cortical) collagen fibrils was studied by electron microscopy.
      Severe abnormalities in collagen fibril structure were detected, at the
      ultrastructural level, in skin and bone specimens from IMO rabbits. In treated
      animals the arrangement of fibrils is anarchic. The overall collagen fibril
      architecture is disturbed compared to normal. IMO collagen fibrils' mean diameter
      values were significantly larger than those from controls, in all examined
      tissues. However, the banding patterns of fibrils were normal in all cases.
      Computer analysis shows no differences in charged amino acid composition between
      IMO and untreated samples. Our results show a correlation between the effects
      induced by osteopenia on skin and bone collagen.

PMID- 9643649
TI  - A contribution to the regulation of proteoglycan production: modulation by TGF
      alpha, TGF beta and IL-1 of glycosaminoglycan biosynthesis on beta-D-xyloside in
      chick embryo fibroblasts.
AB  - In order to elucidate the mechanisms determining the variability in the
      proteoglycan structure and the factors involved in this determination, we treated
      chick embryo skin fibroblasts with beta-D-xyloside to obtain glycosaminoglycan
      chains deprived of core proteins, and with different cytokines (transforming
      growth factor alpha and beta, interleukin-1) to produce variability. The
      different cytokines specifically regulate both cellular and extracellular amount
      and composition of glycosaminoglycans. Beta-D-xyloside treatment does not change
      protein content and protein synthesis, whereas it increases overall extracellular
      sulphated glycosaminoglycan production, heparan sulphate and chondroitin sulphate
      content, and reduces that of dermatan sulphate. This indicates that the core
      protein regulates quantitative proteoglycan production, and probably directs
      (with appropriate signals) the core oligosaccharide bound to it to the right
      synthesizing enzymes. The modulatory action of the different cytokines on
      sulphated glycosaminoglycan production and classes remains, even though the core
      protein is absent. This indicates that the cytokines also act on the
      glycosyltransferases. Our results suggest that the proteoglycan production may be
      subject to a double control, one of which is at the level of the core protein and
      the other, mediated by environmental signals, at the level of glycosaminoglycan
      synthesizing enzymes.

PMID- 9643650
TI  - Heparin sensitive and resistant vascular smooth muscle cells: biology and role in
      restenosis.
AB  - Vascular smooth muscle cells (VSMC)s are characterized by their acute growth
      inhibition by heparin and heparan sulfates; however, recently the isolation of
      VSMCs which display greatly diminished sensitivity to the antiproliferative
      action of heparin have been reported. These heparin resistant (HR) VSMCs have
      been derived through multiple passage of normal rat VSMCs in culture media
      containing high heparin doses, by transformation of VSMCs with oncogene
      containing vectors, or have been isolated from vascular tissues of spontaneously
      hypertensive rats, healthy humans, or humans with restenosis where their presence
      is not limited to sites of injury. Initial characterizations of HR VSMCs are
      reviewed, and here we propose a definition of HR VSMCs. To date the mechanisms
      underlying heparin insensitivity remain elusive. Further study of HR VSMCs may
      expand our understanding of cell growth regulation by heparin, establish whether
      HR VSMCs contribute to the reported failure of heparin to combat restenosis in
      humans, and identify cellular mechanisms driving certain vascular proliferative
      diseases.

PMID- 9643651
TI  - Hsp47 binds to the KDEL receptor and cell surface expression is modulated by
      cytoplasmic and endosomal pH.
AB  - Hsp47 is a novel glycoprotein that binds specifically to procollagen and is
      retained in the ER by its COOH-terminus RDEL peptide sequence (Satoh, M. et al.
      Jol. Cell Biol. 1996; 133: 469-83). In this paper, we report that erd2P, the KDEL
      receptor, is distributed, coprecipitates with, and binds to Hsp47. Also, under
      stress conditions and lowering of pHi, the cytoplasmic epitope of erd2P is not
      recognized by erd2P antibodies unless the cells are pretreated with NEM.
      Coincident with the masking of the cytoplasmic epitope of erd2P, following
      lowering of pHi, Hsp47 is not retained but eludes its retention receptor to be
      expressed on the cell surface. Alkalization of the endosomal compartments by
      treatment with NH4Cl or chloroquine also results in the loss of Hsp47 to the cell
      surface, presumably by inhibiting the retrieval of trans-Golgi network proteins
      from the cell surface. The expression of Hsp47 on the cell surface under
      conditions of stress and alteration of pHi and pHe posture Hsp47 as a serpin
      family protein that may modulate cell migration during development and invasion
      and metastasis in cancer.

PMID- 9643652
TI  - Mechanical role of elastin-associated microfibrils in pig aortic elastic tissue.
AB  - The contribution of microfibrils to the mechanical performance of the meshwork of
      elastic tissue in mature pig aorta was investigated by comparing the properties
      of autoclaved tissue containing elastin and microfibrils with autoclaved tissue
      that had been treated with dithiothreitol (DTT) or hot alkali to remove the
      microfibrils from the elastin. The uniaxial tensile stress-strain curve of the
      autoclaved tissue was linear to a strain of 0.6 or 0.7 and increased nonlinearly
      up to the breaking strain. The nonlinearity at high strains could not be
      accounted for by nonGaussian behavior and was attributed to the progressive
      alignment of the elastic fibers with strain. Removal of the microfibrils with DTT
      or treatment with calcium reduced the modulus at low strains by 12% and 4%
      respectively and increased the modulus at high strains, suggesting that the
      microfibrils have the capacity to change the orientation of the elastin fibers,
      possibly transmitting some of the load from one elastin fiber to another. Our
      findings suggest two possible roles for the microfibrils in vivo: distributing
      the load throughout the elastic fibers of the arterial wall and direct load
      bearing. The modulus and the breaking stress of the rings decreased linearly with
      the duration of alkali treatment starting immediately. By 45 min the modulus had
      dropped by 30% and the breaking stress by 50%, even though the amino acid content
      of the extract gave little evidence of elastin hydrolysis. Alkali treatment
      should not be used on autoclaved pig aortic tissue to be used for mechanical
      testing.

PMID- 9643653
TI  - Identification and localization of type IV collagen chains in the inner ear
      cochlea.
AB  - Mutations in the genes encoding the alpha3(IV), alpha4(IV) and alpha5(IV) chains
      of type IV collagen have been implicated in the pathogenesis of Alport's
      syndrome, a hereditary disorder characterized by progressive nephropathy and
      sensorineural deafness. The known expression of these chains in kidney basement
      membranes supports the contention that they play a crucial role in the
      ultrafiltration function. Whether they play a role in auditory signal
      transduction remains unknown as heretofore, they have not been identified in the
      inner ear. In the present study, the expression of type IV collagen in cochlea of
      the inner ear of guinea pigs was determined. All six alpha-chains of type IV
      collagen were identified by biochemical and immunological methods. By indirect
      immunofluorescence, alpha1(IV) and alpha2(IV) chains were localized to the spiral
      limbus, basilar membrane and tectorial membrane. The alpha3(IV), alpha4(IV),
      alpha5(IV) and alpha6(IV) chains localized exclusively to the tectorial membrane
      and basilar membrane. These results suggest a possible role of type IV collagen
      chains in the active tuning of the basilar and tectorial membrane, an essential
      step in frequency discrimination and amplification of auditory signals.

PMID- 9643654
TI  - Autonomic innervation of the bovine testis.
AB  - The autonomic nerve supply of the bovine testis is investigated in animals of
      different ages by means of immunohistochemistry. Staining with antiserum to
      protein gene product 9.5 gives the most complete results for the study of the
      general innervation pattern. Autonomic nerves reach the testis by three different
      routes: with the blood vessels of the spermatic cord (funicular nervous
      contribution), by the mesorchium (mesorchial nervous contribution) and by the
      ligamentous bridge between epididymal tail and testis (caudal nervous
      contribution). The vessels of the spermatic cord are densely innervated. The
      large vessels of the vascular layer within the tunica albuginea display a
      discontinuous innervation pattern. In the interior of the testis, the caudal half
      of the gonad is completely free of any innervation. Slight differences in
      arrangement and fiber composition of testicular nerves in calves and bulls point
      to a reduction of the innervation with advancing age. The vast majority of bovine
      testicular nerves are dopamine-beta-hydroxylase-positive postganglionic
      sympathetic axons with vasomotor function. There is no evidence for a cholinergic
      innervation of the bovine testis. About half of the bovine testicular nerves are
      neuropeptide Y-immunoreactive. In the adult, solitary calcitonin gene-related
      peptide-immunoreactive fibers are the only ones independent of blood vessels. The
      absence of an innervation in the caudal half of the testis underlines the
      importance of local factors and blood-borne substances for the regulation of
      intratesticular blood flow in the bovine.

PMID- 9643655
TI  - Corticosterone induces hypoactivity of prolactin-immunoreactive cells.
AB  - In order to determine whether corticosterone regulates activity of rat
      lactotrophs by acting directly at the pituitary level, immunohistochemical
      studies were carried out in adrenalectomized rats, subjected or not to treatment
      with corticosterone or colchicine, and in monolayer cultures after incubation
      with corticosterone. Adrenalectomy increased cellular and nuclear areas (p<0.01)
      of prolactin-immunoreactive cells without affecting their cytoplasmic area.
      Similar results were found in adrenalectomized and colchicine-treated animals.
      Corticosterone reversed the effects of adrenalectomy, although normal values were
      partially reversed. In cultured pituitary cells, exposure to corticosterone
      reduced numerical density and cellular, cytoplasmic and nuclear areas with
      respect to control dishes. Morphological differences in shape, arrangement and
      nuclear features were observed after treatment with corticosterone. These results
      demonstrate an inhibitory effect of corticosterone on the activity of rat
      pituitary prolactin cells and suggest that corticosterone induces hypoactivity by
      acting on the pituitary prolactin cells of male rats.

PMID- 9643656
TI  - Organization of the hypobranchial motor column of the clearnose skate, Raja
      eglanteria, with comparisons to tetrapods.
AB  - Motoneurons that supply the clearnose skate's hypobranchial musculature, via the
      occipital nerve and first seven ventral spinal nerve roots, are located within a
      column that extends from a level just caudal to the obex through the
      corresponding rostral spinal cord segments. Individual muscle motoneuron pools
      within the column are considerably intermingled and overlap. Comparisons with
      tetrapods, particularly mammals, where the hypobranchial musculature is greatly
      modified, reveal general conserved features. The motor column's multisegmental
      organization is retained although, in mammals, the column begins rostrally at
      medullary levels, where hypobranchial muscle motoneurons are intimately
      associated with motoneurons to lingual muscles, and it is restricted caudally to
      fewer spinal cord segments. In addition, despite an intermingling of motoneurons
      that supply individual hypobranchial muscles there is a shared rostrocaudal
      sequence of the motor pools. Rostral most hypobranchial motoneurons supply the
      most ventral and anterior muscles (i.e., m. coracomandibularis, and likely m.
      coracohyoideus, of skate and the suprahyoid musculature, m. geniohyoideus, of
      tetrapods). Caudal hypobranchial motoneurons supply the skate's mm.
      coracohyomandibularis, coracoarcualis communis and coracobranchialis and the
      tetrapod's entire infrahyoid muscle complex. The intermingling of multisegmental
      motoneuron populations innervating different hypobranchial muscles might be
      attributed to intermixing of premuscle mesoderm derived from several postotic
      somites but the musculotopic organization along the rostrocaudal axis indicates
      that pre- and posthyoid muscle mesoderm may partially keep its identity during
      its migration to the floor of the pharynx and oral cavity.

PMID- 9643657
TI  - Microvascularization in trigeminal ganglion of the common tree shrew (Tupaia
      glis).
AB  - Since there is only a limited number of studies of the blood supply to the
      trigeminal ganglion (TG) in mammalian species, the TG from 16 common tree shrews
      (Tupaia glis) were investigated by light microscope, transmission electron
      microscope (TEM) and the corrosion cast technique in conjunction with scanning
      electron microscope (SEM). It was found that the TG contained clusters of neurons
      in the peripheral region whereas the bundles of nerve fibers were located more
      centrally. Each ganglionic neuron had a concentric nucleus and was ensheathed by
      satellite cells. It was noted that blood vessels of a continuous type were
      predominantly found in the area where the neurons were densely located and were
      much less frequently observed in the area occupied by nerve fibers. With TEM, the
      TG was shown to be mainly associated with large neurons containing big nuclei and
      prominent nucleoli. The blood supply of the TG is derived from the most rostral
      branch of the pontine artery, from the stapedial artery or sometimes from the
      supraorbital artery, and from the accessory meningeal artery which is a branch of
      the maxillary artery passing through the foramen ovale. These arteries give off
      branches and become capillary networks in the ganglion before draining blood to
      the peripheral region. The veins at the medial border drained into the cavernous
      sinus directly or through the inferior hypophyseal vein, while those at the
      lateral side of the ganglion carried the blood into the pterygoid plexus via an
      accessory meningeal vein. The veins along the trigeminal nerve root joined the
      posterior part of the cavernous sinus. These studies establish a unique
      anatomical distribution of the TG blood supply in the tree shrew and the utility
      of the cast/SEM technique in discerning detailed features of the blood supply in
      the nervous system.

PMID- 9643658
TI  - Morphology of holes in aponeuroses as caused by perforating nerves or vessels at
      the medial epicondyle of the elbow.
AB  - In the present paper the morphology of holes in aponeuroses of origin of muscles
      is generally modelled. These holes result from perforations of the aponeuroses by
      nerves or vessels, or from joints which are crossed by the line of origin of the
      aponeurosis. The concept of aponeurotic holes as morphological entities
      comprehensively explains frequent small-scale anatomic variations in muscles,
      such as muscles with multiple separate origins in parallel. It also contributes
      to a better understanding of nerve compressions and their surgical treatment. The
      model is illustrated by dissection results of the aponeuroses at the medial
      epicondyle of the elbow, which are typically perforated by the n. medianus, the
      a. brachialis, and the n. ulnaris.

PMID- 9643659
TI  - Congenital tibial aplasia with preaxial polydactyly. A case report.
AB  - An anatomical study of a left lower limb with congenital tibial aplasia and
      preaxial polydactyly amputated at 10 months of age was carried out. The tibia was
      replaced by a fibrous band (a band of connective tissue) and there were four
      cuneiforms, six metatarsal bones and seven toes. The second metatarsal bone
      showed characteristics of the hallux. An intermuscular septum which showed an
      orifice for the anterior tibial artery was found on the medial side of the leg
      and foot. All the muscles of the leg and foot were present except for the
      tibialis posterior muscle, which was replaced by two atypical muscles. No
      muscular attachments reached the fibrous band. Several intertendinous connection
      bands were found. Also, an accessory muscular belly split from the tibialis
      anterior tendon and attached to the common flexor tendinous sheet of the foot. An
      unusual motor branch of the deep peroneal nerve ran together with this belly to
      supply the intrinsic muscles of the hallux. We also observed other minor
      anomalies of the nerve pattern. The arterial pattern was complete, except for
      some arteries which showed both an anomalous origin and course. The findings of
      this study suggest that the development of the skeletal elements plays an
      important role in the differentiation of the muscles, tendons, arteries and
      nerves. We postulate that a dysmorphogenic event involving the development of the
      tibial field of the limb could give rise to both defective histodifferentiation
      of the tibia and defective programmed cell death in the pre-hallucial anlage.
      These anomalies would determine secondary adaptations of muscles, tendons,
      vessels and nerves of the limb.

PMID- 9643660
TI  - A generic morphological model of the anatomic variability in the m. flexor
      digitorum profundus, m. flexor pollicis longus and mm. lumbricales complex.
AB  - In the present study a generic model is presented of the anatomic variability in
      the muscle group formed by the m. flexor digitorum profundus, m. flexor pollicis
      longus and mm. lumbricales. This model provides a hypothesis about the structural
      causes of the frequent interdependence of tendons and muscle bellies in this
      muscle group. The model considers the muscle group as composed of two simple
      elementary building blocks: the monogastric contractile units of the FDP-FPL, and
      the digastric contractile elements of the lumbrical, and shows that these units
      can be assembled into complex entities, to which in reality a third structural
      element, the synovial membranes, not discussed in the present paper, adds a
      further complexity. The model allows to generate homologues of the existing
      anatomical variants, which are illustrated by typical dissection results. The
      present study should be of relevance to the morphologist, embryologist, surgeon,
      and musician/pedagogue. To the morphologist, it presents an alternative method of
      description or understanding of anatomic variability, based on (i) the 'atomary'
      concept that the anatomic structure is assembled from simple basic elements, and
      (ii) the local spatial constraints. To the embryologist, it raises the question
      to what degree the 'atomary' anatomical components of this model, which describes
      the macroscopic anatomy of the muscle group in detail, have an embryological
      basis. To the surgeon, the study presents detailed information about the scope of
      the variability in the deep flexor group, and the nature of its intertendinous
      connections. To the musician/pedagogue, it presents a visual illustration of the
      congenital interdependence of the muscles and tendons of an important finger
      motor group, as a possible cause of lack in finger independence which may hamper
      a fluent instrumental technique.

PMID- 9643661
TI  - Diagnosis and management of seminal vesicle cysts associated with ipsilateral
      renal agenesis: a pooled analysis of 52 cases.
AB  - OBJECTIVE: Seminal vesicle cysts combined with ipsilateral renal agenesis
      represent a rare urological anomaly. We searched the literature to review the
      clinical presentation, diagnosis and therapeutic treatment options of this
      anomaly. METHODS: A pooled analysis was performed of 52 cases of seminal vesicle
      cysts combined with ipsilateral renal agenesis, including our own observation.
      The evaluation included: patient age at diagnosis, race, laterality (R/L),
      presence of ureteral remnant in the cyst, presenting symptoms, diagnostic
      examinations, treatment and outcome. RESULTS: The mean age at diagnosis was 30.2
      years. The majority presented in the 2nd, 3rd and 4th decade of their lives. Only
      2 patients (4%) were of African origin, all others were Caucasians. The
      distribution R:L was 2:1. Ureteral remnants were present in 14 patients (27%).
      The most common symptoms were: dysuria (37%), frequency (33%), perineal pain
      (29%), epididymitis (27%), pain following ejaculation (21%) and scrotal pain
      (13%). Infertility was found in 9 patients (17%). The cyst was palpable by
      digital rectal examination in 79%. All patients underwent intravenous urography,
      and 88% underwent cystoscopy. Other frequently performed investigations are:
      ultrasonography (27%), CT scanning (27%), vasovesiculography (46%) and
      urethrocystography (23%). The final treatment was open surgery in 74%, aspiration
      in 6%, transurethral deroofing of the cyst in 6% and spontaneous rupture in 4%.
      In 6% no treatment was given and in 4% the treatment is unknown. All patients
      were free of symptoms after open exploration. The success rates after
      transurethral deroofing and aspiration were 75 and 30% respectively. CONCLUSION:
      Seminal vesicle cysts combined with ipsilateral renal agenesis are a rare
      urological anomaly, occurring in men in the 2nd to 4th decade of their life. They
      present with symptoms of bladder irritation and obstruction and with pain in the
      perineum and scrotum. Epididymitis is frequently found. The diagnostic work-up
      consists of a digital rectal examination, transrectal and abdominal
      ultrasonography, CT scan and a cystoscopy. Open surgery and transurethral
      deroofing of the cyst give excellent results (100 and 75% cure respectively).
      Aspiration of the cyst should only be used for diagnostic purposes.

PMID- 9643662
TI  - Gravity cavernosometry and assessment of complete smooth muscle relaxation:
      helpful in the differential diagnosis of cavernous leakage?
AB  - OBJECTIVE: To establish whether the relationship between cavernosal pressures and
      gravitational pressures of infused liquid during gravity cavernosometry is linear
      when complete smooth muscle relaxation is achieved and whether the determination
      of this relationship could be helpful in the differential diagnosis between
      organic and functional cavernous leakage. METHODS: Gravity cavernosometry was
      performed in 50 impotent patients. The cavernosal pressure was measured at at
      least four different gravitational pressures of the infused liquid. RESULTS: A
      linear relationship was obtained in all patients with normal maximal cavernosal
      pressure at gravity cavernosometry. A flat or nonlinear relationship was found in
      those with abnormal maximal pressure, whatever the cause of cavernous leakage.
      CONCLUSIONS: A linear relationship between cavernosal and gravitational pressures
      characterizes complete smooth muscle relaxation during gravity cavernosometry.
      However, the usefulness of the determination of this relationship is not yet
      established.

PMID- 9643663
TI  - A randomised comparison of 'Casodex' (bicalutamide) 150 mg monotherapy versus
      castration in the treatment of metastatic and locally advanced prostate cancer.
AB  - OBJECTIVES: To evaluate the efficacy and tolerability of 'Casodex' monotherapy
      (150 mg daily) for metastatic and locally advanced prostate cancer. METHODS: A
      total of 1,453 patients with either confirmed metastatic disease (M1), or T3/T4
      non-metastatic disease with elevated prostate-specific antigen (M0) were
      recruited into one of two identical, multicentre, randomised studies to compare
      'Casodex' 150 mg/day with castration. The protocols allowed for combined
      analysis. RESULTS: At a median follow-up period of approximately 100 weeks for
      both studies, 'Casodex' 150 mg was found to be less effective than castration in
      patients with metastatic disease (M1) at entry (hazard ratio of 1.30 for time to
      death) with a difference in median survival of 6 weeks. In symptomatic M1
      patients, 'Casodex' was associated with a statistically significant improvement
      in subjective response (70%) compared with castration (58%). Analysis of a
      validated quality-of-life questionnaire proved an advantage for 'Casodex' in
      sexual interest and physical capacity. 'Casodex' had a substantially lower
      incidence of hot flushes compared to castration (6-13% compared with 39-44%) and
      the most commonly reported adverse events were those expected for a potent
      antiandrogen. However, in patients with M0 disease at entry, the data are still
      immature with only 13% of M0 patients having died. An initial analysis of this
      immature data has suggested that the results in these patients may be different
      to those obtained in patients with M1 disease. A further survival analysis in
      patients with M0 disease is therefore planned when the data are more mature.
      CONCLUSIONS: 'Casodex' 150 mg is less effective than castration in patients with
      M1 disease. However, 'Casodex' has shown a benefit in terms of quality of life
      and subjective response when compared to castration and has an acceptable
      tolerability profile. Thus 'Casodex' 150 mg monotherapy is an option for patients
      with M1 prostate cancer for whom surgical or medical castration is not indicated
      or is not acceptable.

PMID- 9643664
TI  - Primary bladder carcinoma in situ: assessment of early BCG response as a
      prognostic factor.
AB  - OBJECTIVES: To evaluate the prognosis of primary bladder carcinoma in situ (CIS)
      according to the response to bacillus Calmette-Guerin (BCG). PATIENTS AND
      METHODS: Twenty-six cases of primary CIS were treated with BCG. Mean, median and
      minimum follow-up periods were 47, 56 and 24 months. At 6 months, the patients
      were evaluated endoscopically and the response was classified as complete,
      partial or failure. RESULTS: Twenty-one patients (80.8%) showed complete response
      to BCG, 3 did so after a second course; 28.5% relapsed or progressed at a mean of
      44 months. Five patients (19.2%) did not respond initially and all progressed in
      a period of 6 months. Early response to BCG was the only significant prognostic
      factor (p < 0.005). CONCLUSIONS: A high- and a low-risk group of bladder CIS can
      be differentiated according to the response to BCG. CIS of the bladder has a poor
      prognosis, and the number of patients who developed progressive disease is
      significantly higher among the nonresponders.

PMID- 9643665
TI  - Significance of bladder neck involvement on progression in superficial bladder
      cancer.
AB  - OBJECTIVES: To determine the significance of bladder neck involvement in
      predicting disease progression in superficial (stage Ta and T1) transitional cell
      carcinoma (TCC) of the urinary bladder. PATIENTS AND METHODS: A series of 277
      patients with newly diagnosed superficial TCCs of the bladder was reviewed, and
      disease progression (to T2 or worse) was considered. The significance of several
      risk factors including bladder neck involvement was assessed in univariate and
      multivariate analysis. RESULTS: Progression occurred in 28 (10.1%) of 277
      patients during a median follow-up period of 7.7 years. Nineteen died of bladder
      cancer. The following variables were found to be statistically significant at the
      univariate analysis (p < 0.05): irritative symptoms, urine cytology, tumor stage,
      involvement of the bladder neck, and tumor grade. Indeed, only involvement of the
      bladder neck, tumor stage, and grade retained their value as independent factors
      for progression at multivariate analysis. Patients were divided into three groups
      according to the number of independent risk factors they had. Groups having none,
      one, and two or three risk factors included 129, 99, and 49 patients with 5-year
      progression rates of 0.8, 4.6 and 27.5%, and 15-year rates of 4.0, 20.1 and
      42.7%, respectively. CONCLUSION: Involvement of the bladder neck is a significant
      and independent risk factor for progression of superficial TCCs in addition to
      the histologic grade and stage. The combination of these three risk factors
      offers better prediction of progression in an individual patient.

PMID- 9643666
TI  - Implantable microballoons: an attractive alternative in the management of
      intrinsic sphincter deficiency.
AB  - PURPOSE: All current bulking agents employed for treating stress urinary
      incontinence (SUI) have significant limitations due to various side effects,
      technical difficulties and inadequate long-term results. Implantable
      microballoons were therefore tested as a new therapeutic modality for female
      urinary incontinence. MATERIAL AND METHODS: The microballoons are implanted with
      a new system which consists of the self-detachable cross-linked silicone balloon,
      biocompatible filler material and a delivery system. Nineteen female patients
      (mean age 63.3 years) with SUI grade 1 or 2 were studied prospectively. Using the
      Blaivas-Olsson classification, 6 patients had stress incontinence type I, 4 had
      type II and 9 had type III. Three to seven balloons (mean 4.2) were implanted per
      patient. Patients were followed up with pad tests (g) and determination of leak
      point pressure (LPP; cm H2O) and maximal urethral closing pressure (Pura max; cm
      H2O) at 1, 3, 6, 12 and 18 months. RESULTS: The biocompatibility of the
      microballoons was excellent. No significant adverse events were associated with
      the procedure. With a mean follow-up of 14.4 months (range 10-18) 42.1% (8/19) of
      the women are dry. In the latter the pad test improved from a preoperative mean
      of 22.6 g (2-75) to 0 and the LPP increased from a preoperative mean of 38.5 cm
      H2O (25-60) to 80.5 cm H2O (68-106). 36.8% (7/19) of the patients showed
      significant improvement of their incontinence. In this group the pad test
      improved from a preoperative mean of 39.1 g (8-112) to 9.7 g (2-29) and LPP from
      a mean of 37.1 cm H2O (25-50) to 42.0 cm H2O (30-58). In 4 patients (21.05%) the
      technique failed. Seven of the 8 cured patients had type III incontinence; the
      eighth patient had type I incontinence. It failed in all patients with type II
      incontinence. CONCLUSION: The implantation of microballoons is a safe, well
      tolerated and clinically effective modality for the treatment of type III SUI,
      i.e. intrinsic sphincter deficiency.

PMID- 9643667
TI  - Long-term results following transurethral resection of the prostate.
AB  - Two subsets of a single-center study population with benign prostatic hyperplasia
      (n(1) = 232; n(2) = 214) undergoing transurethral resection (TUR) of the prostate
      (TURP 1979 and 1995) entered a retrospective study designed to examine the long
      term follow-up. The actual data were assessed with a patient-addressed
      questionnaire. Preoperative voiding patterns did not differ significantly;
      postoperative micturition revealed comparable results for both groups. Mortality
      and TUR syndrome rates were reduced to very low levels. The most significant
      improvement was found in blood transfusions. The postoperative incidence of
      urethral stricture (1.7 vs. 1.5%) or bladder neck contracture (2.7 vs. 2.4%) were
      low and did not alter significantly. Urinary incontinence changed for both
      collectives (11.4 vs. 3.3%). Urodynamic investigations revealed that all (n = 21)
      but 1 of the patients with TURP 1979 had the incontinence due to different
      bladder dysfunctions, but not because of postoperative stress incontinence. The
      questionnaire about the patient's actual contentment after TURP 1979 showed 79%
      of the patients still satisfied, 12% neutral and 9% dissatisfied with their
      micturition. Overall the patients reported a generally favorable view of TURP
      outcome in the long-term follow-up.

PMID- 9643668
TI  - A double-blind comparison of terazosin and tamsulosin on their differential
      effects on ambulatory blood pressure and nocturnal orthostatic stress testing.
AB  - OBJECTIVES: This single-centre, double-blind, randomized parallel-group study
      compared ambulatory blood pressure (AMBP) and heart rate (HR) profiles and
      responses to orthostatic testing (OT) for recommended regimens of tamsulosin
      (TAM, modified release formulation) and terazosin (TER), two alpha1-adrenoceptor
      antagonists that differ in their selectivity for alpha1-adrenoceptor subtypes,
      pharmacokinetic properties and recommended posology for the treatment of lower
      urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO).
      METHODS: 50 elderly normotensive male volunteers (mean age 68 years, range 61-78;
      27 had LUTS) entered a single-blind 24-hour placebo run-in followed by a 15-day
      double-blind treatment in which the TER group received a 1-week treatment with 1
      mg, then 1 week with 2 mg and finally a last dose of 5 mg, each dose administered
      once daily in the evening, while TAM subjects received 0.4 mg once daily after
      breakfast throughout. Subjects had AMBPs and OT while hospitalized on four
      occasions: during the placebo run-in and subsequent to the first dose of 1, 2 and
      5 mg TER or at corresponding times under TAM. Regular OT (blood pressure after 5
      min supine and after 2 min standing) was carried out between 6:00 and 6:30 a.m.;
      'nocturial' OT took place whenever the subject had to leave the bed at night to
      void. RESULTS: The baseline blood pressure values were slightly higher in the TAM
      group, but under treatment there was little difference between the treatments
      with regard to circadian changes in AMBP and HR. Under TER, there were 10
      incidents of symptomatic hypotensive OT in 9 subjects (2 with syncope);
      furthermore, there were 24 events of asymptomatic exaggerated (> or = 20 mm Hg)
      decrease in systolic blood pressure in 12 subjects. With TAM in contrast, there
      was only 1 subject who experienced symptomatic hypotensive OT on 3 occasions
      (this subject had a previous history of vertigo and ought not to have been
      included); 7 subjects on TAM showed 16 incidents of asymptomatic hypotensive OT.
      The difference between TER and TAM was statistically significant for the number
      of subjects with positive symptomatic OT (p = 0.011). CONCLUSION: Once-daily
      dosing of TAM after breakfast at a fixed dose level (0.4 mg) offers a more
      efficient protection against undesired cardiovascular extension effects in the
      normotensive elderly treated for LUTS suggestive of BPO than the usually
      recommended treatment schedule of TER with step-up doses (1-5 mg) administered at
      night.

PMID- 9643669
TI  - Nephrectomy: A comparative study between the transperitoneal and retroperitoneal
      laparoscopic versus the open approach.
AB  - OBJECTIVES: Different techniques have been introduced to perform laparoscopic
      nephrectomy using either the transperitoneal or the retroperitoneal route.
      However, to date only few data exist comparing the results and morbidity of these
      procedures as well as with the standard technique of open nephrectomy. MATERIAL
      AND METHODS: This paper compares the clinical results of 18 transperitoneal
      laparoscopic nephrectomies (TLN) for benign renal disease with 17 retroperitoneal
      laparoscopic nephrectomies (RLN) and 19 consecutive open nephrectomies (Nx). All
      groups were comparable in terms of indication. The analysis of clinical data
      included operative time, morbidity, length of analgesic use and postoperative
      hospital stay. RESULTS: The mean operative time for benign disease was 206.5 for
      TLN, 211.2 for RLN and 117 min for open nephrectomy. Analgesic medication
      requirement per patient was 2 days for TLN, 1 day for RLN and 4 days for Nx while
      the postoperative hospital stay averaged 7 days for TLN, 6 days for RLN and 10
      days for Nx. The time of convalescence was 21 days after RLN, 24 days after TLN
      versus 40 days after open nephrectomy. CONCLUSIONS: Our results demonstrate an
      overall clear advantage of a laparoscopic approach when compared to open surgery
      and also reveals distinct benefits of a retroperitoneal approach.

PMID- 9643670
TI  - Results of fibrin glue application therapy in testicular hydrocele.
AB  - Nine patients, mean age 55 years, with testicular hydroceles, were treated by
      aspiration and two-component fibrin glue injection. One patient was treated
      twice. The glue contains 70-110 mg fibrinogen and 500 IU human thrombin in 0.5-
      and 2-ml injections, respectively (Tisseel duo quick, Immune AB). The smaller
      glue volume was used in 4 cases and the larger volume in 6 cases. The average
      volume of hydrocele fluid was 77 (range 60-120) ml. Treatment caused no pain or
      discomfort other than puncture of the skin and no pain-relieving medication was
      required afterwards. In this series there were no infections but one
      conservatively treated hematoma. The hydrocele of that patient disappeared.
      Although the hydroceles recurred in 9 cases during the mean follow-up of 3.5
      months, in 2 patients the hydroceles were clinically smaller than the original
      one and symptoms were milder subjectively. Our findings suggest that fibrin
      adhesive glue is not sufficiently effective in treatment of testicular
      hydroceles.

PMID- 9643671
TI  - Bladder washout and stone formation in paediatric enterocystoplasty.
AB  - OBJECTIVE: To review the incidence of stone formation in our patients with
      enterocystoplasty to determine the effect of regular bladder washout. METHODS:
      From 1988 to 1995, a prospective cohort of 30 children underwent enteroplasty
      with continent diversion. Over the same period, a consecutive group of 30
      children had an augmentation alone. All were instructed to wash out their bladder
      on a weekly basis with sterile water. The frequency of the washouts increased if
      there were problems with increasing mucus production. Their incidence of stone
      formation has been compared to a similar group of 30 children performing clean
      intermittent self catheterisation (CISC) on their native bladders. RESULTS: Five
      (17%) children with continent diversions formed bladder stones (mean time to
      formation 35 months, range 13-59 months) were compared with 2 (7%) of children
      with augmentation. No child performing CISC alone formed stones. CONCLUSIONS: A
      regime of regular bladder washout in children with enterocystoplasty did not
      significantly reduce the incidence of stone formation when compared to previously
      published data.

PMID- 9643672
TI  - Culture of human urothelial cells on a cell-free dermis for autotransplantation.
AB  - OBJECTIVE: Techniques for in vitro culturing and autotransplantation have been
      developed for a variety of human cells and are used today in several fields of
      medicine. In reconstructive surgery within the genitourinary tract, autologous
      urothelial cells cultured in vitro could be of considerable value but have not
      yet been used clinically. The aim of this study was to facilitate transplantation
      of cultured urothelium by establishing a reliable method for culturing urothel on
      an immunologically inert and biodegradable structure. METHODS: Normal human
      urothelial cells were cultured in vitro using a feeder-cell system. To achieve an
      optimal carrier structure, cells were removed enzymatically from a split
      thickness skin graft. Human urothelial cells were then seeded on the cell-free
      dermis and incubated in vitro. The seeded dermis samples were investigated
      histologically and with immunohistochemical methods at days 7, 14 and 21.
      RESULTS: The human urothelial cells incubated in vitro reached confluence after 7
      10 days and the cells could be cultured through 9 passages with preserved
      proliferative potential. When the cells were seeded on a cell-free dermis they
      attached, formed colonies and became confluent and stratified up to three cell
      layers after 21 days of incubation. The urothelial origin of the cells was
      confirmed by immunohistochemical staining against cytokeratin. CONCLUSION: The
      advantages of culturing the urothelial cells on a cell-free dermis include a
      short time lag until grafts are available, probably facilitated transplantation
      procedure, transplantation of undifferentiated cells and the formation of a
      vascularised base under the new urothelium. The method described in this study
      may be of great value in providing autologous urothelium for reconstructive
      surgery in the genitourinary tract.

PMID- 9643673
TI  - Optimal parameters for transurethral intravesical electrostimulation determined
      in an experiment in the rat.
AB  - OBJECTIVE: Parameters of current for transurethral intravesical
      electrostimulation (IVES) are studied in the rat to determine the settings which
      elicit optimal detrusor contractions. Action mechanisms related to the induction
      of detrusor contractions upon ives are also investigated. METHODS: In 24 female
      Wistar rats transurethral IVES was performed using 95 combinations of different
      pulse durations and frequencies. The reference electrode was positioned in the
      bladder, in the urethra, or on the abdominal wall. RESULTS AND CONCLUSIONS: The
      optimal detrusor contractions are induced in the rat with a current of 10 Hz
      frequency and 20 ms pulse duration. A mathematical correlation is found between
      frequency and pulse duration which permits to determine the best combination.
      Evidence for the existence of local factors inducing detrusor contractions by
      IVES is given. The detrusor contractions proved independent of the position of
      the reference electrode.

PMID- 9643674
TI  - Neobladder and bladder replacement.

PMID- 9643675
TI  - Human pancreatic secretory trypsin inhibitor. Distribution, actions and possible
      role in mucosal integrity and repair.
AB  - Pancreatic secretory trypsin inhibitor is a potent protease inhibitor which was
      originally identified in the pancreas. It has subsequently been shown to be
      present in mucus-secreting cells throughout the gastrointestinal tract and also
      in the kidney, lung and breast. Its major roles are likely to be to prevent
      premature activation of pancreatic proteases and to decrease the rate of mucus
      digestion by luminal proteases within the stomach and colon. In addition, PSTI
      increases the proliferation of a variety of cell lines and stimulates cell
      migration, possibly acting via the EGF receptor. These findings suggest that PSTI
      may also be involved in both the early and late phases of the healing response
      following injury. Further studies including the production of transgenic
      overexpression and knockout models should help elucidate the physiological
      function of this peptide.

PMID- 9643676
TI  - Increased cytosolic Ca2+ amplifies oxygen radical-induced alterations of the
      ultrastructure and the energy metabolism of isolated rat pancreatic acinar cells.
AB  - BACKGROUND: Oxygen radicals have been implicated as important mediators in the
      early pathogenesis of acute pancreatitis, but the mechanism by which they produce
      pancreatic tissue injury remains unclear. We have, therefore, investigated the
      effects of oxygen radicals on isolated rat pancreatic acinar cells as to the
      ultrastructure, cytosolic Ca2+ concentration and energy metabolism. METHODS:
      Acinar cells were exposed to an oxygen radical-generating system consisting of
      xanthine oxidase, hypoxanthine and chelated iron ions. Cell injury was assessed
      by LDH release and electron microscopy. Cytosolic Ca2+ levels and mitochondrial
      membrane potential were determined by flow cytometry; adenine nucleotide
      concentrations by HPLC. Mitochondrial dehydrogenase activity was measured by
      spectrophotometric assay. RESULTS: Oxygen radicals damaged the plasma membrane as
      shown by a 6-fold LDH increase in the incubation medium within 180 min. At the
      ultrastructural level, mitochondria were the most susceptible to oxidative
      stress. In correlation to the pronounced mitochondrial damage, the mitochondrial
      dehydrogenase activity declined by 70%, whereas the mitochondrial membrane
      potential was enhanced by 27% after 120 min. Together this may cause the 85%
      decrease in the ATP concentration and the corresponding increase in ADP/AMP
      observed in parallel. In addition, an immediate 26% increase in cytosolic Ca2+
      was found, a change which could be inhibited by BAPTA, reducing cellular damage.
      CONCLUSION: Cytosolic Ca2+ synergizes with oxygen radicals causing alterations of
      the ultrastructure and energy metabolism of acinar cells which might contribute
      to the cellular changes found in early stages of acute pancreatitis.

PMID- 9643677
TI  - Pancreatitis-associated protein is upregulated in mouse pancreas during acute
      pancreatitis.
AB  - Pancreatitis-associated protein I (PAP I) is a pancreatic secretory protein
      strongly expressed during acute pancreatitis in the rat and human. We
      hypothesized that its expression was part of a general and coordinated response
      of the organ against aggression. An opposite pattern of PAP I mRNA expression has
      recently been described in the mouse. The murine PAP I mRNA was described to be
      highly expressed in normal pancreas and down-regulated during pancreatitis. The
      important implications of these unexpected findings led us to investigate the
      expression of murine PAP I in cerulein-induced pancreatitis. Northern blot
      analysis demonstrated a very low level of PAP I mRNA in the healthy mouse
      pancreas and strong overexpression during acute pancreatitis. Western blot
      analysis confirmed that changes in pancreatic PAP I levels were parallel to those
      of the mRNA and the protein was localized by immunohistochemistry to the acinar
      cells. It was concluded that, during the course of acute pancreatitis, the
      pattern of PAP I expression in the mouse pancreas was comparable to that already
      observed in the rat and human. Although we have no explanation for the
      discrepancy between our results and those recently reported, the expression
      pattern of PAP I in the mouse exocrine pancreas described in the present study
      suggests that the pancreatic response to aggression might be conserved in
      mammals.

PMID- 9643678
TI  - Immunohistochemical characterization of the pancreatic cellular infiltrate in
      normal pancreas, chronic pancreatitis and pancreatic carcinoma.
AB  - BACKGROUND/AIMS: Chronic pancreatitis is histologically characterized by an
      extended fibrosis and infiltration of leukocytes. We intended to differentiate
      the infiltration to evaluate the inflammatory process. METHODS: Samples of
      tissues of normal pancreas (NP, n = 12), of chronic pancreatitis (CP, n = 7), and
      pancreatic tissues surrounding pancreatic carcinoma (CA, n = 7) were investigated
      by immunohistochemical staining using the APAAP technique. RESULTS: In normal
      pancreas, mononuclear cells (47.1 +/- 26.0 cells/mm2) were observed with a
      predominance of macrophages (56.3%) and T lymphocytes (31.3%) which were
      differentiated in CD8+ lymphocytes (9.3 +/- 7.2 cells/ mm2) and CD4+ lymphocytes
      (6.7 +/- 3.2 cells/mm2). Rarely, plasma cells (5.3%) and B lymphocytes (7.1%)
      could be detected. In pancreatic tissue of patients with CP and in CA there was a
      significant increase of mononuclear cells to 264.4 +/- 120.3 cells/mm2 and 284.3
      +/- 67.8 cells/mm2, respectively. In both diseases percentages of T lymphocytes
      (CP: 50.5%; CA: 48.1%) were higher than in normal controls. CD4+/CD8+ ratio of
      0.77 in CP and 0.82 in CA demonstrated a predominance of CD8+ cells compared to
      the peripheral blood. In NP and CA, nearly all T lymphocytes expressed CD45R0
      identifying memory cells, while only 58% of T lymphocytes were CD45R0 positive in
      CP. CONCLUSION: Our data suggest that the investigated cases of CP were of a
      common inflammatory type rather than due to an autoimmunological reaction. CD8+ T
      lymphocytes were the predominant T cell subset in the inflammatory infiltrates in
      both CP and CA.

PMID- 9643679
TI  - Defending data-monitoring committees.

PMID- 9643680
TI  - Chest pain and normal coronary arteriograms: role of "microvascular spasm".

PMID- 9643681
TI  - BSE: the final resting place.

PMID- 9643682
TI  - Prognostic factors for success of endometrial ablation and resection.

PMID- 9643683
TI  - Health care for seafarers.

PMID- 9643684
TI  - Surgery for congenital dislocation of the hip in the UK as a measure of outcome
      of screening. MRC Working Party on Congenital Dislocation of the Hip. Medical
      Research Council.
AB  - BACKGROUND: Universal clinical screening for congenital dislocation of the hip to
      detect hip instability in neonates was introduced in the UK as a national policy
      in 1969, but its effectiveness is not known. We aimed to assess the extent to
      which surgery for congenital dislocation of the hip is the result of a failure of
      detection through screening or follows non-surgical treatment after detection by
      screening. METHODS: We established a national orthopaedic surveillance scheme and
      used routine hospital data for inpatients for 20% of births in the UK (Scotland
      and the Northern and Wessex regions) to ascertain the number of children aged
      under 5 years per 1000 livebirths who had received at least one operative
      procedure for congenital dislocation of the hip from April, 1993, to April, 1994.
      Estimates of the incidence of operative procedures were adjusted for under
      ascertainment by capture-recapture techniques. FINDINGS: The ascertainment
      adjusted incidence of a first operative procedure for congenital dislocation of
      the hip in the UK was 0.78 per 1000 livebirths (95% CI 0.72-0-84). Congenital
      dislocation of the hip had not been detected by routine screening in 222 (70%) of
      318 children reported to the national orthopaedic surveillance scheme. In 112
      (35%) children the diagnosis was made primarily as a result of parental concern.
      67 (21%) children had previously received non-surgical treatment. In Scotland and
      the Northern and Wessex regions, 81 cases were notified to the national
      orthopaedic surveillance scheme, 62 cases were identified only through routine
      hospital data on inpatients, and an estimated 20 cases were not identified by
      either source, making a total of 163 cases. Thus, 81 (50%) of these 163 cases
      were identified by surveillance, 125 (77%) by routine data, and 143 (88%) by both
      sources. INTERPRETATION: The incidence of a first operative procedure for
      congenital dislocation of the hip in the UK was similar to that reported before
      screening was introduced. In most children who received surgery, congenital
      dislocation of the hip was not detected by screening. Formal evaluation of
      current and alternative screening policies, including universal primary
      ultrasound imaging, is needed.

PMID- 9643685
TI  - Randomised comparison of primary stent placement versus primary angioplasty
      followed by selective stent placement in patients with iliac-artery occlusive
      disease. Dutch Iliac Stent Trial Study Group.
AB  - BACKGROUND: Percutaneous transluminal angioplasty (PTA) is a safe, simple, and
      successful treatment for intermittent claudication caused by iliac-artery
      occlusive disease. Primary stent placement has been proposed as more effective
      than PTA. We compared the technical results and clinical outcomes of two
      treatment strategies-primary placement of a stent across the stenotic segment of
      the iliac artery, or primary PTA followed by selective stent placement when
      haemodynamic results were inadequate. METHODS: We randomly assigned 279 patients
      with intermittent claudication, recruited from departments of vascular surgery,
      either to direct stent placement (group I, n=143) or primary angioplasty (group
      II, n=136), with subsequent stent placement in case of a residual mean pressure
      gradient greater than 10 mm Hg across the treated site. The main inclusion
      criterion was intermittent claudication on the basis of iliac-artery stenosis of
      more than 50%, proven by angiography. All patients had a clinical assessment
      before intervention and at 3, 12, and 24 months. Clinical success was defined as
      improvement of at least one clinical category. Secondary endpoints were initial
      technical results, procedural complications, cumulative patency as assessed by
      duplex ultrasonography, and quality of life. FINDINGS: In group II, selective
      stent placement was done in 59 (43%) of the 136 patients. The mean follow-up was
      9.3 months (range 3-24). Initial haemodynamic success and complication rates were
      119 (81%) of 149 limbs and 6 (4%) of 143 limbs (group I) versus 103 (82%) of 126
      limbs and 10 (7%) of 136 limbs (group II), respectively. Clinical success rates
      at 2 years were 29 (78%) of 37 patients and 26 (77%) of 34 patients in groups I
      and II, respectively (p=0.6); however, 43% and 35% of the patients, respectively,
      still had symptoms. Quality of life improved significantly after intervention
      (p<0.05) but we found no difference between the groups during follow-up. 2-year
      cumulative patency rates were similar at 71% versus 70% (p=0.2), respectively, as
      were reintervention rates at 7% versus 4%, respectively (95% CI -2% to 9%).
      INTERPRETATION: There were no substantial differences in technical results and
      clinical outcomes of the two treatment strategies both at short-term and long
      term follow-up. Since angioplasty followed by selective stent placement is less
      expensive than direct placement of a stent, the former seems to be the treatment
      of choice for lifestyle-limiting intermittent claudication caused by iliac artery
      occlusive disease.

PMID- 9643686
TI  - Role of human-milk lactadherin in protection against symptomatic rotavirus
      infection.
AB  - BACKGROUND: Human milk contains a 46 kDa mucin-associated glycoprotein,
      lactadherin, which binds specifically to rotavirus and inhibits its replication.
      This study tested the hypothesis that lactadherin protects against symptoms of
      rotavirus infection. METHODS: 200 infants in Mexico City were recruited at birth
      and monitored by regular stool EIA for rotavirus, serology, and recording of
      feeding and stool patterns. Milk samples were obtained from the mothers weekly
      until 4 weeks post partum then monthly. The sample taken immediately before an
      infant's episode of rotavirus infection was assayed for lactadherin,
      butyrophilin, mucin, and secretory IgA. An infection was defined as symptomatic
      if diarrhoea occurred in the 5 days before or after detection of the virus.
      FINDINGS: 31 infants developed rotavirus infection; 15 were symptomatic and 16
      had no symptoms. The median concentration of lactadherin in the milk samples
      (obtained 4-41 days [median 13] before the infection) was 48.4 (range 5.6-180)
      microg/mL in the asymptomatic group and 29-2 (6.2-103-4) microg/mL in the
      symptomatic group. Although these medians did not differ significantly, in
      logistic regression analysis adjusted for age at infection and secretory IgA
      concentration there was a significant difference between the groups (p=0O01). No
      association between symptom status and concentrations of butyrophilin, mucin, or
      secretory IgA was found. INTERPRETATION: Protection against rotavirus by human
      milk is associated with the glycoprotein lactadherin. This association is
      independent of products of the secretory immune system.

PMID- 9643687
TI  - Angina pectoris caused by coronary microvascular spasm.
AB  - BACKGROUND: Microvascular angina can occur during exercise and at rest. Reduced
      vasodilator capacity of the coronary microvessels is implicated as a cause of
      angina during exercise, but the mechanism of angina at rest is not known. Our aim
      was to test the hypothesis that primary hyperconstriction (spasm) of coronary
      microvessels causes myocardial ischaemia at rest. METHODS: Acetylcholine induces
      coronary artery spasm in patients with variant angina. We tested the effects of
      intracoronary acetylcholine at graded doses in 117 consecutive patients with
      chest pain (at rest, during exertion, or both) and no flow-limiting (>50%)
      organic stenosis in the large epicardial coronary arteries. We also assessed the
      metabolism of myocardial lactate during acetylcholine administration in 36 of the
      patients by measurement of lactate in paired blood samples from the coronary
      artery and coronary sinus vein. FINDINGS: Of the 117 patients, 63 (54%) had large
      artery spasm, 29 (25%) had microvascular spasm, and 25 (21%) had atypical chest
      pain. The 29 patients with microvascular spasm developed angina-like chest pain,
      ischaemic electrocardiogram (ECG) changes, or both spontaneously (two patients)
      or after administration of acetylcholine (27 patients) without spasm of the large
      epicardial coronary arteries. Testing of paired samples of arterial and coronary
      sinus venous blood showed that lactate was produced during angina attack in nine
      of 11 patients with microvascular spasm. There was more women (p<0.01) and fewer
      coronary risk factors (p<0.01) in patients with microvascular spasm than in those
      with large-artery spasm. INTERPRETATION: Coronary microvascular spasm and
      resultant myocardial ischaemia may be the cause of chest pain in a subgroup of
      patients with microvascular angina.

PMID- 9643689
TI  - A man who lost weight and his sight.

PMID- 9643688
TI  - Expression of genes that contribute to proliferative and metastatic ability in
      breast cancer resected during various menstrual phases.
AB  - BACKGROUND: Retrospective studies show significant improvements in survival among
      women who had breast cancer resected during the luteal phase of their menstrual
      cycle compared with the follicular phase. We hypothesised that tumour tissue
      would show cyclical changes in expression of genes whose products might
      contribute to metastatic potential. METHODS: We studied 32 premenopausal women
      with operable breast cancer. We assayed hormones to define more accurately the
      menstrual phase during which surgery was done. We used northern blot analysis of
      RNA from fresh-frozen tumour specimens to study the patterns of expression of
      genes for proteolytic enzymes (cysteine proteinase cathepsin L and aspartyl
      proteinase cathepsin D; matrix metalloproteinases MMP-9 and MMP-2), tissue
      inhibitors of metalloproteinases TIMP-1 and TIMP-2, and TP53. RESULTS: There was
      a significantly higher level of expression of RNA for cathepsin L, MMP-9, and
      TP53 (p=0.005, 0.03, 0.03, respectively) in tumours that were resected during the
      follicular and periovulatory phases of the menstrual cycle than at other times in
      the cycle. A similar but non-significant trend was seen for MMP-2 and cathepsin
      D. A non-significant trend in the opposite direction was seen for TIMP-1 and TIMP
      2. INTERPRETATION: We found that tumour expression of genes that may contribute
      to proliferative capacity and metastatic potential can change in breast cancer
      during the course of the menstrual cycle. The finding could provide a molecular
      explanation for the reports of improved survival in some breast-cancer patients
      whose tumours were removed during the luteal phase of the menstrual cycle. Larger
      studies are required to extend our study, assess mechanisms of gene regulation,
      and verify any relevant influence in long-term survival.

PMID- 9643690
TI  - Explosive spread of HIV-1 and sexually transmitted diseases in Cambodia.

PMID- 9643691
TI  - Immunosuppressive drugs and HHV-8 in a patient with a renal transplant and
      Kaposi's sarcoma.

PMID- 9643692
TI  - Treatment of cutaneous leishmaniasis with nitric-oxide donor.

PMID- 9643693
TI  - Do doctors have an increased rate of Caesarean section?

PMID- 9643694
TI  - Ooplasmic injections of secondary spermatocytes for non-obstructive azoospermia.

PMID- 9643695
TI  - Pancreatitis after losartan.

PMID- 9643696
TI  - Reporting of attributable and relative risks, 1966-97.

PMID- 9643697
TI  - Avoidable deaths from vehicle accidents in Modena, Italy.

PMID- 9643698
TI  - 3-year follow-up of patients randomised in the metoprolol in dilated
      cardiomyopathy trial. The Metoprolol in Dilated Cardiomyopathy (MDC) Trial Study
      Group.

PMID- 9643699
TI  - Cryptococcosis and starling nests.

PMID- 9643700
TI  - Inhaled nitric oxide and inhibition of platelet aggregation in critically ill
      neonates.

PMID- 9643701
TI  - Endurance training during a twin pregnancy in a marathon runner.

PMID- 9643702
TI  - Adverse drug reactions remain a major cause of death.

PMID- 9643703
TI  - Genetic basis for idiopathic scoliosis brought a step nearer.

PMID- 9643704
TI  - Retinoids promising in Kaposi's sarcoma trials.

PMID- 9643705
TI  - Telomeres: keys to senescence and cancer.

PMID- 9643706
TI  - A happy season for biomedical research.

PMID- 9643707
TI  - Austria investigates illegal blood trade.

PMID- 9643708
TI  - Failed coronary thrombolysis.

PMID- 9643709
TI  - Thalidomide: was the tragedy preventable?

PMID- 9643710
TI  - 150 years of pharmacovigilance.

PMID- 9643711
TI  - A sort of progress.

PMID- 9643712
TI  - Interpretation of Thrombosis Prevention Trial.

PMID- 9643713
TI  - Interpretation of Thrombosis Prevention Trial.

PMID- 9643714
TI  - Interpretation of Thrombosis Prevention Trial.

PMID- 9643715
TI  - Interpretation of Thrombosis Prevention Trial.

PMID- 9643716
TI  - Interpretation of Thrombosis Prevention Trial.

PMID- 9643717
TI  - Interpretation of Thrombosis Prevention Trial.

PMID- 9643718
TI  - Interpretation of Thrombosis Prevention Trial.

PMID- 9643719
TI  - Early amniocentesis for biochemical genetic prenatal diagnosis.

PMID- 9643720
TI  - Disease burden in sub-Saharan Africa.

PMID- 9643721
TI  - Disease burden in sub-Saharan Africa.

PMID- 9643722
TI  - Hepatitis C.

PMID- 9643723
TI  - Hepatitis C.

PMID- 9643724
TI  - Hepatitis C.

PMID- 9643725
TI  - Antiepileptic drugs in developing countries.

PMID- 9643726
TI  - Lack of specificity of procalcitonin for sepsis diagnosis in premature infants.

PMID- 9643727
TI  - First clinical isolate of vancomycin-intermediate Staphylococcus aureus in a
      French hospital.

PMID- 9643728
TI  - Height measurements and stretching.

PMID- 9643729
TI  - Fish consumption and major depression.

PMID- 9643730
TI  - Food rations for refugees.

PMID- 9643731
TI  - HIV-1 infection and prostitutes.

PMID- 9643732
TI  - Need for holistic view of illness.

PMID- 9643733
TI  - Futility and surgeons.

PMID- 9643734
TI  - Misled by moonshine.

PMID- 9643735
TI  - Medical advocacy for the oppressed.

PMID- 9643736
TI  - ISAAC--a hypothesis generator for asthma? International Study of Asthma and
      Allergies in Childhood.

PMID- 9643737
TI  - Catechol-O-methyltransferase inhibitors for treatment of Parkinson's disease.

PMID- 9643738
TI  - What risk of infection with IUD use.

PMID- 9643739
TI  - Torticollis--what is straight ahead?

PMID- 9643740
TI  - Training in orthopaedic spinal surgery.

PMID- 9643741
TI  - Worldwide variation in prevalence of symptoms of asthma, allergic
      rhinoconjunctivitis, and atopic eczema: ISAAC. The International Study of Asthma
      and Allergies in Childhood (ISAAC) Steering Committee.
AB  - BACKGROUND: Systematic international comparisons of the prevalences of asthma and
      other allergic disorders in children are needed for better understanding of their
      global epidemiology, to generate new hypotheses, and to assess existing
      hypotheses of possible causes. We investigated worldwide prevalence of asthma,
      allergic rhinoconjunctivitis, and atopic eczema. METHODS: We studied 463,801
      children aged 13-14 years in 155 collaborating centres in 56 countries. Children
      self-reported, through one-page questionnaires, symptoms of these three atopic
      disorders. In 99 centres in 42 countries, a video asthma questionnaire was also
      used for 304,796 children. FINDINGS: We found differences of between 20-fold and
      60-fold between centres in the prevalence of symptoms of asthma, allergic
      rhinoconjunctivitis, and atopic eczema, with four-fold to 12-fold variations
      between the 10th and 90th percentiles for the different disorders. For asthma
      symptoms, the highest 12-month prevalences were from centres in the UK,
      Australia, New Zealand, and Republic of Ireland, followed by most centres in
      North, Central, and South America; the lowest prevalences were from centres in
      several Eastern European countries, Indonesia, Greece, China, Taiwan, Uzbekistan,
      India, and Ethiopia. For allergic rhinoconjunctivitis, the centres with the
      highest prevalences were scattered across the world. The centres with the lowest
      prevalences were similar to those for asthma symptoms. For atopic eczema, the
      highest prevalences came from scattered centres, including some from Scandinavia
      and Africa that were not among centres with the highest asthma prevalences; the
      lowest prevalence rates of atopic eczema were similar in centres, as for asthma
      symptoms. INTERPRETATION: The variation in the prevalences of asthma, allergic
      rhinoconjunctivitis, and atopic-eczema symptoms is striking between different
      centres throughout the world. These findings will form the basis of further
      studies to investigate factors that potentially lead to these international
      patterns.

PMID- 9643742
TI  - Randomised, double-blind, placebo-controlled trial of human recombinant growth
      hormone in patients with chronic heart failure due to dilated cardiomyopathy.
AB  - BACKGROUND: Some studies have suggested that treatment with recombinant human
      growth hormone (rhGH) increases left-ventricular mass and improves haemodynamic
      and functional status in patients with heart failure due to dilated
      cardiomyopathy. We did a double-blind, randomised, placebo-controlled study of
      rhGH in patients with chronic heart failure due to dilated cardiomyopathy.
      METHODS: 50 patients (43 men) were randomly allocated treatment with subcutaneous
      rhGH (2 IU daily) or placebo for a minimum of 12 weeks. The primary endpoints
      were the effects on left-ventricular mass and systolic wall stress. The secondary
      endpoints were the effects on left-ventricular size and function. Data were
      analysed by intention to treat. FINDINGS: Patients in the rhGH group had an
      increase in left-ventricular mass compared with those in the placebo group (27%,
      p=0.0001). There was no significant difference in left-ventricular systolic wall
      stress, mean blood pressure, or systemic vascular resistance between the two
      groups. New York Heart Association functional class, left-ventricular ejection
      fraction, and distance on the 6 min walking test were unchanged. The change in
      serum insulin-like growth factor (IGF)-I concentrations (rhGH 77 ng/mL; placebo 
      19 ng/mL, GH vs placebo p=0.0001) was significantly related to the change in left
      ventricular mass (r=0.55, p=0.0001). One patient in the rhGH group was withdrawn
      at 6 weeks because of worsening heart failure. INTERPRETATION: There is a
      significant increase in left-ventricular mass in patients with dilated
      cardiomyopathy given rhGH but this is not accompanied by an improvement in
      clinical status. Changes in left-ventricular mass are related to changes in serum
      IGF-I concentrations. Whether a longer treatment period would provide clinical
      benefits and decrease mortality is unknown.

PMID- 9643743
TI  - Complications of use of intrauterine devices among HIV-1-infected women.
AB  - BACKGROUND: A WHO expert group and the International Planned Parenthood
      Federation recommend against use of intrauterine devices (IUDs) in HIV-1-infected
      women based on theoretical concerns about pelvic infection and increased blood
      loss. We investigated whether the risk of complications after IUD insertion is
      higher in HIV-1-infected women than in non-infected women. METHODS: 649 (156 HIV
      1 infected 493 non-infected) women in Nairobi, Kenya, who requested and met local
      eligibility criteria for insertion of an IUD were enrolled. We gathered
      information on IUD-related complications, including pelvic inflammatory disease,
      removals due to infection, pain, or bleeding, expulsions, and pregnancies at 1
      and 4 months after insertion. Patients' HIV-1 status was masked from physicians.
      FINDINGS: Complications were identified in 48 of 615 women (11 [7.6%] HIV-1
      infected women, 37 [7.9%] non-infected). Incident pelvic inflammatory disease
      (two [1.4%] HIV-1 infected, one [0.2%] non-infected) and infection-related
      complications (any tenderness, removal of IUD for infection or pain; ten [6.9%]
      HIV-1 infected, 27 [5.7%] non-infected) were also rare and similar in the two
      groups. Complication rates were similar by CD4 (immune) status. Multivariate
      analyses suggested no association between HIV-1 infection and increased risks for
      overall complications (odds ratio 0.8 [95% CI 0.4-1.7]) or infection-related
      complications (1.0 [0.5-2.3]), adjusted for marital status, study site, previous
      IUD use, ethnic origin, and frequency of sexual intercourse, but a slight
      increase cannot be ruled out. INTERPRETATION: Our data suggest that IUDs may be a
      safe contraceptive method for appropriately selected HIV-1-infected women with
      continuing access to medical services.

PMID- 9643744
TI  - Mass screening for lung cancer with mobile spiral computed tomography scanner.
AB  - BACKGROUND: The incidence of and mortality from lung cancer have increased
      steadily. Most lung cancers are not localised when first detected, but early
      detection is mandatory to improve prognosis. Since curable early cases are hard
      to visualise with conventional chest radiography, a new diagnostic means must be
      found. We assessed whether population-based mass screening with a spiral computed
      tomography scanner could contribute substantially to detection of smaller
      cancers, and decrease mortality. METHODS: In 1996, we screened in a mobile unit
      5483 individuals from the general population of Matsumoto, Japan, aged between 40
      years and 74 years who had undergone annual chest radiography (miniature
      fluorophotography) and cytological assessment of sputum. All participants had a
      low-dose X-ray spiral computed tomography (CT) scan of the thorax; 3967 also
      underwent miniature fluorophotography. We compared smokers and non-smokers.
      Further assessments were done for probably benign but suspicious lesions;
      suspicion of cancer; and indeterminate small nodules by chest radiography and
      conventional CT, with additional transbronchial biopsy when possible. Thoracotomy
      was recommended when it was strongly suspected that the patients had lung cancer.
      FINDINGS: 19 patients were diagnosed as having lung cancer--14 with suspicion of
      lung cancer, three with benign but suspicious lesions, and two with indeterminate
      small nodules. 18 cases were surgically confirmed, and one was clinically
      diagnosed. The mean size of lesions was 17 mm (range 6-47). In four of 19
      patients, lung abnormality was seen on CT and miniature fluorophotography. The
      lung-cancer detection rate with CT was 0.48%, significantly higher than the 0.03
      0.05% for standard mass assessments done previously in the same area. CT missed
      one case that was found solely on a sputum cytology examination. INTERPRETATION:
      Our results show that miniature fluorophotography or conventional chest
      radiography, which have been the main diagnostic techniques for lung cancer,
      showed few small cancers. CT was more accurate in mass screening for lung cancer
      and led to early detection and an accurate diagnosis of lung cancer, and should
      be considered in future health plans.

PMID- 9643745
TI  - Malaria in Maremma, Italy.
AB  - BACKGROUND: In August, 1997, a woman with no history of travel to malarious
      regions developed Plasmodium vivax malaria. She lived in a rural area of Italy
      where indigenous Anophyles labranchiae mosquitoes were present. METHODS AND
      FINDINGS: An environmental investigation was done within a 3 km radius of the
      patient's house. Adult mosquitoes and larvae were collected and examined by PCR
      with the gene for plasmodium circumsporozoite protein as target. About 200 people
      living in the area were interviewed to detect possible carriers of P. vivax.
      FINDINGS: None of the mosquitoes captured were carrying any malarial organisms.
      The house-to-house investigation identified a 7-year-old girl who had had a
      feverish illness a few days after her arrival in Italy from India, and who, 3
      months later, still had P. vivax in her blood; she and her mother had
      antimalarial antibodies. INTERPRETATION: These investigations suggest that the
      index case of malaria was caused by local anopheline mosquitoes infected with
      exogenous P. vivax.

PMID- 9643746
TI  - Teapot myositis.

PMID- 9643747
TI  - Single-surgeon thoracoscopic surgery with a voice-controlled robot.

PMID- 9643748
TI  - Terlipressin-exacerbated hypokalaemia.

PMID- 9643749
TI  - Two subtypes of HIV-1 among injection-drug users in southern China.

PMID- 9643750
TI  - Genotype at codon 129 and susceptibility to Creutzfeldt-Jakob disease.

PMID- 9643751
TI  - Pregnancy in women with observed focal nodular hyperplasia of the liver.

PMID- 9643752
TI  - Renal dysfunction accompanying oral creatine supplements.

PMID- 9643754
TI  - Pro-convulsant effects of oral melatonin in neurologically disabled children.

PMID- 9643753
TI  - PlA2 polymorphism and efficacy of aspirin.

PMID- 9643755
TI  - Chlamydia pneumoniae in vascular tissues from heart-transplant donors.

PMID- 9643756
TI  - Systemic absorption of progesterone from Progest cream in postmenopausal women.

PMID- 9643757
TI  - Lamivudine-induced paronychia.

PMID- 9643758
TI  - Issue of lower limit for LDL cholesterol unresolved.

PMID- 9643759
TI  - Peter Barnes: a breath of fresh air in asthma research.

PMID- 9643760
TI  - North Korea: where children look like old men.

PMID- 9643761
TI  - Antidepressant dependence controversy moves to Internet.

PMID- 9643763
TI  - Country profile: India.

PMID- 9643764
TI  - Altering molecular mechanisms to prevent sudden arrhythmic death.
AB  - Trials of drug treatment for prevention of sudden arrhythmic death have been
      disappointing, perhaps because suppressive therapy with arrhythmic agents fails
      to address the mechanisms leading to electrophysiological failure. We propose
      that preventive treatment should pay more attention to molecular mechanisms
      responsible for the progression of cardiac disease to electrophysiological
      failure. Most sudden cardiac deaths occur in people with atherogenic
      dyslipidaemias. Our hypothesis is that the pathogenic molecular mechanisms of
      dyslipidaemias contribute directly to arrhythmogenesis. Proinflammatory
      prothrombotic lipid-derived mediators that may play a part in arrhythmogenesis
      include phospholipids and leucotrienes acting through the platelet-activating
      factor and peroxisome proliferator-activated-receptor pathways. There are drugs
      available to test the hypothesis of dyslipidaemias-specific prevention of
      electrophysiological failure.

PMID- 9643765
TI  - Setting targets to address inequalities in health.

PMID- 9643766
TI  - Effectiveness of pneumococcal vaccine.

PMID- 9643767
TI  - Effectiveness of pneumococcal vaccine.

PMID- 9643768
TI  - Effectiveness of pneumococcal vaccine.

PMID- 9643769
TI  - Effectiveness of pneumococcal vaccine.

PMID- 9643770
TI  - Lung transplantation.

PMID- 9643771
TI  - Do Asian HBV carriers differ from non-Asian carriers?

PMID- 9643772
TI  - Azithromycin, the multidrug-resistant protein, and cystic fibrosis.

PMID- 9643773
TI  - Iron overload and mitochondrial diseases.

PMID- 9643774
TI  - Minimal residual disease in children with acute lymphoblastic leukaemia.

PMID- 9643775
TI  - Telomere shortening in recipients of bone-marrow transplants.

PMID- 9643776
TI  - Intravenous immunoglobulins and transforming growth factor beta.

PMID- 9643777
TI  - Homocysteine and endothelial vascular function.

PMID- 9643778
TI  - Quinolone-resistant Salmonella typhi in Vietnam.

PMID- 9643779
TI  - New-variant Creutzfeldt-Jakob disease and treatment of haemophilia. Executive
      Committee UK Haemophilia Directors' Organisation.

PMID- 9643780
TI  - Ligase chain reaction assay for Chlamydia trachomatis during the menstrual cycle.

PMID- 9643781
TI  - Laser pointers: the facts, media hype, and hysteria.

PMID- 9643782
TI  - Medicine and modern physics.

PMID- 9643783
TI  - Chronic fatigue syndrome.

PMID- 9643785
TI  - "Let no man name death to me".

PMID- 9643784
TI  - Hard sell on health.

PMID- 9643786
TI  - Defensible secrecy, a very rare bird.

PMID- 9643787
TI  - Action against antibiotic resistance: no time to lose.

PMID- 9643788
TI  - Teaching heart-failure patients how to breathe.

PMID- 9643789
TI  - Biomarkers of asthma.

PMID- 9643790
TI  - Not all fat is alike.

PMID- 9643791
TI  - Use of selective serotonin-reuptake inhibitors or tricyclic antidepressants and
      risk of hip fractures in elderly people.
AB  - BACKGROUND: Tricyclic antidepressants (TCAs) are associated with an increased
      risk of falls and hip fractures in elderly people. Selective serotonin-reuptake
      inhibitors (SSRIs) are reported to be better tolerated than TCAs. We investigated
      the risk of hip fractures associated with SSRIs and TCAs. METHODS: This case
      control study used administrative healthcare data from the province of Ontario,
      Canada. 8239 cases-patients aged 66 years or older, treated in hospital between
      April, 1994, and March, 1995, for hip fracture-were each matched for age and sex
      to five controls. Logistic regression was used to calculate the odds ratio for
      hip fracture with adjustment for potential confounding effects produced by
      concomitant drug use and comorbidity. FINDINGS: With participants who had no
      exposure to antidepressants as the reference category, the adjusted odds ratio
      for hip fracture was 2.4 (95% CI 2.0-2.7) for exposure to SSRIs, 2.2 (1.8-2.8)
      for exposure to secondary-amine TCAs, and 1.5 (1.3-1.7) for exposure to tertiary
      amine TCAs. For all types of antidepressants, current use was associated with a
      higher risk of hip fracture than former use. The odds ratios for hip fracture
      were higher for new current users than for continuous current users in all three
      drug classes. The proportion of current use in the low-dose range was 22% for
      SSRIs, 50% for secondary-amine TCAs, and 58% for tertiary-amine TCAs.
      INTERPRETATION: Exposure to any of the three classes of antidepressants is
      associated with a significant increase in the risk of hip fracture. Despite
      differences in dose distribution, this analysis suggests that SSRIs do not offer
      an advantage over TCAs in terms of risk of hip fracture.

PMID- 9643792
TI  - Effect of breathing rate on oxygen saturation and exercise performance in chronic
      heart failure.
AB  - BACKGROUND: In chronic heart failure (CHF), impaired pulmonary function can
      independently contribute to oxygen desaturation and reduced physical activity. We
      investigated the effect of breathing rate on oxygen saturation and other
      respiratory indices. METHODS: Arterial oxygen saturation (SaO2) and respiratory
      indices were recorded during spontaneous breathing (baseline) and during
      controlled breathing at 15, six, and three breaths per min in 50 patients with
      CHF and in 11 healthy volunteers (controls). 15 patients with CHF were randomly
      allocated 1 month of respiratory training to decrease their respiratory rate to
      six breaths per min. Respiratory indices were recorded before training, at the
      end of training, and 1 month after training. FINDINGS: During spontaneous
      breathing, mean SaO2 was lower in CHF patients than in controls (91-4% [SD 0.4]
      vs 95.4% [0.2], p<0.001). Controlled breathing increased SaO2 at all breathing
      rates in patients with CHF. Compared with baseline, minute ventilation increased
      at 15 breaths per min (+45.9% [9.8], p<0.01), did not change at six breaths per
      min, and decreased at three breaths per min (-40.3% [4.8], p<0.001). In the nine
      CHF patients who had 1 month of respiratory training, resting SaO2 increased from
      92.5% (0.3) at baseline to 93.2% (0.4) (p<0.05), their breathing rate per min
      decreased from 13.4 (1.5) to 7.6 (1.9) (p<0.001), peak oxygen consumption
      increased from 1157 (83) to 1368 (110) L/min (p<0.05), exercise time increased
      from 583 (29) to 615 (23) min/s (p<0.05), and perception of dyspnoea reduced from
      a score of 19.0 (0.4) to 17.3 (0.9) on the Borg scale (p<0.05). There were no
      changes in the respiratory indices in the patients who did not have respiratory
      training. INTERPRETATION: Slowing respiratory rate reduces dyspnoea and improves
      both resting pulmonary gas exchange and exercise performance in patients with
      CHF.

PMID- 9643793
TI  - Is current eye-care-policy focus almost exclusively on cataract adequate to deal
      with blindness in India?
AB  - BACKGROUND: India's National Programme for Control of Blindness focuses almost
      exclusively on cataract, based on a national survey done in the 1980s which
      reported that cataract caused 80% of the blindness in India. No current
      population-based data on the causes of blindness in India are available. We
      assessed the rate and causes of blindness in an urban population in southern
      India. METHODS: We selected 2954 participants by stratified, random, cluster,
      systematic sampling from Hyderabad city. Eligible participants were interviewed
      and given a detailed ocular assessment, including visual acuity, refraction,
      slitlamp biomicroscopy, applanation intraocular pressure, gonioscopy, dilatation,
      grading of cataract, stereoscopic fundus assessment, and automated-threshold
      visual fields. FINDINGS: 2522 participants, including 1399 aged 30 years or more,
      were assessed. 49 participants (all aged > or =30 years) were blind (presenting
      distance visual acuity <6/60 or central visual field <200 in the better eye). The
      rate of blindness among those aged 30 years or more, adjusted for age and sex,
      was 3.08% ([95% CI 1.95-4.21]). Causes included cataract (29.7%), retinal disease
      (17.1%), corneal disease (15.4%), refractive error (12.5%), glaucoma (12.1%), and
      optic atrophy (11.0%). 15.7% of the blindness caused by visual-field constriction
      would have been missed without visual-field examination. Also without visual
      field and detailed dilated-fundus assessments, blindness attributed to cataract
      would have been overestimated by up to 75.8%. If the use of cataract surgery in
      this urban population was half that found in this study, which simulates the
      situation in rural India, cataract would have caused 51.8% (39.4-64.2) of
      blindness, significantly less than the 80% accepted by current policy.
      INTERPRETATION: Much of the blindness in this Indian population was due to non
      cataract causes. The previous national survey did not include detailed dilated
      fundus assessment and visual-field examination which could have led to
      overestimation of cataract as a cause of blindness in India. Policy-makers in
      India should encourage well-designed population-based epidemiological studies
      from which to develop a comprehensive long-term policy on blindness in addition
      to dealing with cataract.

PMID- 9643794
TI  - Bronchodilator S-nitrosothiol deficiency in asthmatic respiratory failure.
AB  - BACKGROUND: Nitric oxide (NO) gas concentrations are high in the expired air of
      individuals with asthma, but not consistently so in the expired air of people
      with pneumonia. S-nitrosothiols are naturally occurring bronchodilators, the
      concentrations of which are raised in the airways of patients with pneumonia.
      Airway S-nitrosothiols have not been studied in asthma. METHODS: Tracheal S
      nitrosothiol concentrations from eight asthmatic children in respiratory failure
      were compared with those of 21 children undergoing elective surgery. RESULTS:
      Mean S-nitrosothiol concentrations in asthmatic children were lower than in
      normal children (65 [SD 45] nmol/L vs 502 [SD 429] nmol/L) and did not vary with
      inspired oxygen concentration or airway thiol concentration. INTERPRETATION:
      Severe asthma is associated with low concentrations of airway S-nitrosothiols.
      This is the first reported deficiency of an endogenous bronchodilator in the
      human asthmatic airway lining fluid. We suggest that S-nitrosothiol metabolism
      may be a target for the development of new asthma therapies.

PMID- 9643795
TI  - Cellular cytotoxic response induced by DNA vaccination in HIV-1-infected
      patients.
AB  - BACKGROUND: DNA vaccination is known to generate immune responses against HIV-1
      in animal models. We aimed to assess the efficacy of DNA vaccination in induction
      of immune responses in HIV-1-infected human beings. METHODS: Nine symptom-free
      HIV-1-infected patients were immunised with DNA constructs encoding the nef, rev,
      or tat regulatory genes of HIV-1. The patients were selected for having no or low
      antibody reactivities to these antigens. HIV-1-specific cytotoxic T-lymphocytes
      (CTLs), precursor frequencies, and antigen-specific proliferative responses were
      measured before, during, and after three immunisations over 6 months. FINDINGS:
      Cellular immune reactivities against the HIV-1 regulatory proteins were absent or
      low before DNA immunisation. DNA vaccination induced detectable memory cells in
      all patients and specific cytotoxicity in eight patients. CTLs were MHC-class-I
      restricted and mainly of CD8+ origin. In three patients the cellular activity was
      transient, decreasing after an initial response. INTERPRETATION: DNA immunisation
      with HIV-1 genes can induce specific cellular responses in human beings with no
      apparent side-effects. It is theoretically possible that HIV-1-specific cytotoxic
      responses to regulatory proteins could lead to infected cells being eliminated
      before they have released new viral particles. However, it is possible that the
      patients we selected responded less than would non-selected or non-infected
      individuals. The small number of patients presented here does not allow
      generalisation of our findings.

PMID- 9643796
TI  - A woman who trembled, then had chorea.

PMID- 9643797
TI  - No evidence for measles, mumps, and rubella vaccine-associated inflammatory bowel
      disease or autism in a 14-year prospective study.

PMID- 9643798
TI  - Severe premature coronary artery disease with protease inhibitors.

PMID- 9643799
TI  - Hormone-receptor status of breast cancer in Papua New Guinea.

PMID- 9643800
TI  - Presence of donor-specific DNA in plasma of kidney and liver-transplant
      recipients.

PMID- 9643801
TI  - A urinary marker for multiple sclerosis.

PMID- 9643803
TI  - Improvement in renal cholesterol emboli syndrome after simvastatin.

PMID- 9643802
TI  - HSV-1 in brain and risk of Alzheimer's disease.

PMID- 9643804
TI  - Health anxiety in medical students.

PMID- 9643805
TI  - UK drug misusers targeted for better clinical care.

PMID- 9643806
TI  - USA continues federal ban on needle-exchange funding.

PMID- 9643807
TI  - Thwarting the dwindling progression of cachexia.

PMID- 9643808
TI  - Labour's disappointing first year for health.

PMID- 9643810
TI  - From mustard gas to biowarfare--Congress tackles military medicine.

PMID- 9643811
TI  - Onchocerciasis.

PMID- 9643812
TI  - Critical ethical issues in clinical trials with xenotransplants.

PMID- 9643813
TI  - Early gastric cancer: disease or pseudo-disease?

PMID- 9643814
TI  - The poetry of genetics: or reading a genetic sequence--a literary model for
      cellular mechanisms.

PMID- 9643815
TI  - Autism, inflammatory bowel disease, and MMR vaccine.

PMID- 9643816
TI  - Autism, inflammatory bowel disease, and MMR vaccine.

PMID- 9643817
TI  - Autism, inflammatory bowel disease, and MMR vaccine.

PMID- 9643818
TI  - Autism, inflammatory bowel disease, and MMR vaccine.

PMID- 9643819
TI  - Autism, inflammatory bowel disease, and MMR vaccine.

PMID- 9643820
TI  - Autism, inflammatory bowel disease, and MMR vaccine.

PMID- 9643821
TI  - Autism, inflammatory bowel disease, and MMR vaccine.

PMID- 9643822
TI  - Autism, inflammatory bowel disease, and MMR vaccine.

PMID- 9643823
TI  - Autism, inflammatory bowel disease, and MMR vaccine.

PMID- 9643824
TI  - Questions on breast-implants study.

PMID- 9643825
TI  - Survival of patients with breast cancer and BRCA1 mutations.

PMID- 9643826
TI  - Prenatal exposure to famine and health in later life.

PMID- 9643827
TI  - Prenatal exposure to famine and health in later life.

PMID- 9643828
TI  - Prenatal exposure to famine and health in later life.

PMID- 9643829
TI  - Magnetic-resonance imaging in breast cancer.

PMID- 9643830
TI  - Aboriginal health.

PMID- 9643832
TI  - Sexual ill-health among blacks in the UK.

PMID- 9643831
TI  - Aboriginal health.

PMID- 9643833
TI  - World health.

PMID- 9643834
TI  - World health.

PMID- 9643835
TI  - Clinical experience of UK medical students.

PMID- 9643836
TI  - Number-needed-to-treat to prevent one death.

PMID- 9643837
TI  - China's trade in human organs.

PMID- 9643838
TI  - Hereditary breast cancer, circa 1750.

PMID- 9643839
TI  - Pyoderma gangrenosum.

PMID- 9643841
TI  - Global public health: targeting inequities.

PMID- 9643842
TI  - Private venture galvanizes public effort on Human Genome Project.

PMID- 9643843
TI  - Cancer experts offer healthy dose of skepticism toward hype over antiangiogenesis
      agents.

PMID- 9643844
TI  - Guarded endorsement for Lyme disease vaccine.

PMID- 9643845
TI  - From the Centers for Disease Control and Prevention. Prevalence and impact of
      chronic joint symptoms--seven states, 1996.

PMID- 9643846
TI  - From the Centers for Disease Control and Prevention. Strategies for providing
      follow-up and treatment services in the National Breast and Cervical Cancer Early
      Detection Program--United States, 1997.

PMID- 9643847
TI  - Patients' views of direct access to specialists: an Israeli experience.
AB  - CONTEXT: Surveys carried out among users of medical services can be a useful tool
      for health care organizations in designing proper services. Specifically,
      patients' views of direct access to specialists can be useful to health
      organizations considering the gatekeeper model. OBJECTIVE: To assess patients'
      opinions about direct access to specialists and referral to specialists through
      their primary care physician. DESIGN: An intercept survey, in which patients were
      interviewed at the randomly selected service provision sites, was carried out in
      3 districts in Israel during 1995. A total of 1445 and 1289 patients were
      interviewed in primary care and specialty clinics, respectively. SETTING: Primary
      care and specialty clinics in 3 regions in Israel serving 750000 members of Kupat
      Holim Clalit, Israel's largest sick fund. PARTICIPANTS: Hebrew-speaking members
      of Kupat Holim Clalit who visited the primary care or specialty clinics in the 3
      regions during the study period. MAIN OUTCOME MEASURES: Rate of preferences for
      direct access to specialists and preferences for referral through primary care
      physician. RESULTS: Fifty-two percent of the respondents preferred direct access
      to specialists, while 48% preferred a referral from their primary care physician.
      Multivariate logistic regression analysis indicated that the preference for
      direct access was significantly lower among patients older than 45 years (odds
      ratio [OR], 0.75; 95% confidence interval [CI], 0.62-0.91); patients whose
      primary care physician was a specialist in family medicine (OR, 0.80; 95% CI,
      0.67-0.97); and patients who were satisfied with their primary care physician
      (OR, 0.34; 95% CI, 0.27-0.44). Preference for direct access was significantly
      higher among more highly educated patients (OR, 1.38; 95% CI, 1.16-1.65) and
      patients residing in Jerusalem (OR, 2.46; 95% CI, 2.05-2.95) and those younger
      than 45 years who were dissatisfied with their family physician or a primary care
      physician who was not board certified. If direct access was not available, 33% of
      respondents would leave the sick fund and 48% would remain; 19% did not know.
      CONCLUSIONS: Informing sick fund members, particularly the younger and more
      educated among them, about the advantages of consulting with the primary care
      physician, as well as providing specialty training in family medicine to primary
      care physicians, may reduce patients' preference for direct access to
      specialists.

PMID- 9643848
TI  - Zafirlukast and Churg-Strauss syndrome.

PMID- 9643849
TI  - Zafirlukast and Churg-Strauss syndrome.

PMID- 9643850
TI  - Zafirlukast and Churg-Strauss syndrome.

PMID- 9643851
TI  - Quality of care for elderly patients with pneumonia.

PMID- 9643852
TI  - Quality of care for elderly patients with pneumonia.

PMID- 9643853
TI  - Quality of care for elderly patients with pneumonia.

PMID- 9643854
TI  - Time lag bias in publishing clinical trials.

PMID- 9643855
TI  - Time lag bias in publishing clinical trials.

PMID- 9643856
TI  - CCR5 genotype and mother-to-child HIV transmission.

PMID- 9643857
TI  - Maternal smoking and inhibition of fetal growth factor.

PMID- 9643858
TI  - Fasting insulin and apolipoprotein B levels and low-density lipoprotein particle
      size as risk factors for ischemic heart disease.
AB  - CONTEXT: Epidemiological studies have established a relationship between
      cholesterol and low-density lipoprotein cholesterol (LDL-C) concentrations and
      the risk of ischemic heart disease (IHD), but up to half of patients with IHD may
      have cholesterol levels in the normal range. OBJECTIVE: To assess the ability to
      predict the risk of IHD using a cluster of nontraditional metabolic risk factors
      that includes elevated fasting insulin and apolipoprotein B levels as well as
      small, dense LDL particles. DESIGN: Nested case-control study. SETTING: Cases and
      controls were identified from the population-based cohort of the Quebec
      Cardiovascular Study, a prospective study conducted in men free of IHD in 1985
      and followed up for 5 years. PARTICIPANTS: Incident IHD cases were matched with
      controls selected from among the sample of men who remained IHD free during
      follow-up. Matching variables were age, smoking habits, body mass index, and
      alcohol consumption. The sample included 85 complete pairs of nondiabetic IHD
      cases and controls. MAIN OUTCOME MEASURES: Ability of fasting insulin level,
      apolipoprotein B level, and LDL particle diameter to predict IHD events, defined
      as angina, coronary insufficiency, nonfatal myocardial infarction, and coronary
      death. RESULTS: The risk of IHD was significantly increased in men who had
      elevated fasting plasma insulin and apolipoprotein B levels and small, dense LDL
      particles, compared with men who had normal levels for 2 of these 3 risk factors
      (odds ratio [OR], 5.9; 95% confidence interval [CI], 2.3-15.4). Multivariate
      adjustment for LDL-C, triglycerides, and high-density lipoprotein cholesterol
      (HDL-C) did not attenuate the relationship between the cluster of nontraditional
      risk factors and IHD (OR, 5.2; 95% CI, 1.7-15.7). On the other hand, the risk of
      IHD in men having a combination of elevated LDL-C and triglyceride levels and
      reduced HDL-C levels was no longer significant (OR, 1.4; 95% CI, 0.5-3.5) after
      multivariate adjustment for fasting plasma insulin level, apolipoprotein B level,
      and LDL particle size. CONCLUSION: Results from this prospective study suggest
      that the measurement of fasting plasma insulin level, apolipoprotein B level, and
      LDL particle size may provide further information on the risk of IHD compared
      with the information provided by conventional lipid variables.

PMID- 9643859
TI  - Zinc gluconate lozenges for treating the common cold in children: a randomized
      controlled trial.
AB  - CONTEXT: The common cold is one of the most frequently occurring illnesses and is
      responsible for substantial morbidity and economic loss. Biochemical evidence
      suggests that zinc may be an effective treatment, and zinc gluconate glycine
      (ZGG) lozenges have been shown to reduce the duration of cold symptoms in adults.
      OBJECTIVE: To determine the efficacy of ZGG treatment of colds in children and
      adolescents. DESIGN: A randomized, double-masked, placebo-controlled study.
      SETTING: Two suburban school districts in Cleveland, Ohio. PATIENTS: A total of
      249 students in grades 1 through 12 were enrolled within the first 24 hours of
      experiencing at least 2 of 9 symptoms of the common cold. INTERVENTION: Zinc
      lozenges, 10 mg, orally dissolved, 5 times a day (in grades 1-6) or 6 times a day
      (in grades 7-12). MAIN OUTCOME MEASURES: Time to resolution of cold symptoms
      based on subjective daily symptom scores for cough, headache, hoarseness, muscle
      ache, nasal congestion, nasal drainage, scratchy throat, sore throat, and
      sneezing. RESULTS: Time to resolution of all cold symptoms did not differ
      significantly between students receiving zinc (n = 124) and those receiving
      placebo (n = 125) (median, 9 days; 95% confidence interval [CI], 8-9 days;
      median, 9 days, 95% CI, 7-10 days, respectively; P=.71). There were no
      significant differences in the time to resolution of any of the 9 symptoms
      studied. Compared with controls, more students in the zinc group reported adverse
      effects (88.6% vs 79.8%; P=.06); bad taste (60.2% vs 37.9%; P=.001); nausea
      (29.3% vs 16.1%; P=.01); mouth, tongue, or throat discomfort (36.6% vs 24.2%;
      P=.03); and diarrhea (10.6% vs 4.0%; P=.05). CONCLUSIONS: In this community
      based, randomized controlled trial, ZGG lozenges were not effective in treating
      cold symptoms in children and adolescents. Further studies with virologic testing
      are needed to clarify what role, if any, zinc may play in treating cold symptoms.

PMID- 9643860
TI  - Impact of risk-adjusting cesarean delivery rates when reporting hospital
      performance.
AB  - CONTEXT: Hospitals and health plans are often ranked on rates of cesarean
      delivery, under the assumption that lower rates reflect more appropriate, more
      efficient care. However, most rankings do not account for patient factors that
      affect the likelihood of cesarean delivery. OBJECTIVE: To compare hospital
      cesarean delivery rates before and after adjusting for clinical risk factors that
      increase the likelihood of cesarean delivery. DESIGN: Retrospective cohort study.
      SETTING: Twenty-one hospitals in northeast Ohio. PATIENTS: A total of 26127 women
      without prior cesarean deliveries admitted for labor and delivery from January
      1993 through June 1995. MAIN OUTCOME MEASURES: Hospital rankings based on
      observed and risk-adjusted cesarean delivery rates. RESULTS: The overall cesarean
      delivery rate was 15.9% and varied (P<.001) from 6.3% to 26.5% in individual
      hospitals. Adjusted rates varied from 8.4% to 22.0%. The correlation between
      unadjusted and adjusted hospital rankings (ie, 1-21) was only modest (R=0.35,
      P=.12). Whereas 7 hospitals were classified as outliers (ie, had rates higher or
      lower [P<.05] than overall rate) on the basis of both unadjusted and adjusted
      rates, outlier status changed for 5 hospitals (24%), including 2 that changed
      from outliers to nonoutliers, 2 that changed from nonoutliers to outliers, and 1
      that changed from a high outlier to a low outlier. CONCLUSIONS: Cesarean delivery
      rates varied across hospitals in a single metropolitan region. However, rankings
      that fail to account for clinical factors that increase the risk of cesarean
      delivery may be methodologically biased and misleading to the public.

PMID- 9643861
TI  - Gastrostomy placement and mortality among hospitalized Medicare beneficiaries.
AB  - CONTEXT: Although the use of feeding tubes among older individuals stirs
      considerable controversy, population-based descriptive data regarding patient
      outcomes are scarce. OBJECTIVE: To describe hospitalized Medicare beneficiaries
      having gastrostomies placed and their associated mortality rates. DESIGN:
      Retrospective cohort study. SETTING AND PATIENTS: Hospitalized Medicare
      beneficiaries aged 65 years or older discharged in 1991 following gastrostomy
      placement (excluding individuals in health maintenance organizations). MAIN
      OUTCOME MEASURES: Mortality at 30 days, 1 year, and 3 years following gastrostomy
      and characteristics of individuals undergoing gastrostomy placement. RESULTS: In
      1991, claims reflecting gastrostomy insertion were submitted for 81105 older
      Medicare beneficiaries following hospital discharge. The in-hospital mortality
      rate was 15.3%. Cerebrovascular disease, neoplasms, fluid and electrolyte
      disorders, and aspiration pneumonia were the most common primary diagnoses. The
      overall mortality rate at 30 days was 23.9% (95% confidence interval [CI], 23.65%
      24.2%), reaching 63.0% (95% CI, 62.7%-63.4%) at 1 year and 81.3% (95% CI, 81.0%
      81.5%) by 3 years. One in 131 white and 1 in 58 black Medicare beneficiaries aged
      85 years or older was discharged alive or deceased from a hospital in 1991
      following gastrostomy placement. CONCLUSIONS: Gastrostomies are frequently placed
      in older individuals and more often in blacks; mortality rates following
      placement are substantial.

PMID- 9643862
TI  - Public health implications of antiretroviral therapy and HIV drug resistance.
AB  - Widespread use of antiretroviral agents and increasing occurrence of human
      immunodeficiency virus (HIV) strains resistant to these drugs have given rise to
      a number of important issues. Some of these concerns are distinct from the
      obvious question of the relationship between drug resistance and treatment
      failure and have potentially widespread public health implications. The relevant
      issues include but are not limited to the following: (1) frequency with which
      drug-resistant virus may be transmitted via sexual, intravenous, or mother-to
      child routes; (2) ability of drug-resistant variants to be transmitted, a
      question that relates, in part, to the relative fitness of such strains; (3)
      effectiveness of antiviral therapy in diminishing viral burden in both blood and
      genital secretions, and whether this may be compromised in persons harboring
      resistant virus; and (4) importance of patient adherence to antiviral therapy and
      its relationship to sustained reduction in viral load to minimize the appearance
      in and transmission of drug-resistant virus from both blood and genital
      secretions. Thus, prevention of both development of HIV drug resistance as well
      as transmission of drug-resistant variants is a central issue of public health
      importance. Unless this topic is appropriately addressed, the likelihood is that
      drug-resistant variants of HIV, if able to successfully replicate, will sustain
      the epidemic and limit the effectiveness of antiviral therapy.

PMID- 9643863
TI  - Antiretroviral drug resistance testing in adults with HIV infection: implications
      for clinical management. International AIDS Society--USA Panel.
AB  - OBJECTIVES: To review current knowledge of the biology and clinical implications
      of human immunodeficiency virus (HIV) resistance to antiretroviral drugs,
      describe assays for measuring resistance, and assess their use in clinical
      practice. PARTICIPANTS: The International AIDS Society-USA assembled a panel of
      13 physicians with expertise in basic science, clinical research, and patient
      care relevant to HIV resistance to antiretroviral drugs. EVIDENCE: We reviewed
      available data from published reports and presented at national and international
      research conferences. Basic science research, clinical trial results, and expert
      opinions were used to form the basis of this report. Data on methods for and
      characteristics of specific genotypic and phenotypic assays were obtained from
      manufacturers and service providers. CONSENSUS PROCESS: The panel met regularly
      between October 1997 and April 1998. Panel subgroups developed and discussed
      different sections of the report before discussing them with the entire panel.
      Conclusions and suggested approaches to the use of resistance testing were
      determined by group consensus. CONCLUSIONS: Plasma HIV RNA level and CD4+ cell
      count are the primary values that should be used to guide the initiation of
      antiretroviral therapy and subsequent changes in therapy. Possible causes of
      treatment failure other than development of drug resistance that should be
      considered are adherence, drug potency, and pharmacokinetic issues. Genotypic and
      phenotypic testing for HIV resistance to antiretroviral drugs may prove useful
      for individual patient management. Assays under development need validation,
      standardization, and a clearer definition of their clinical roles. Possible
      current roles of resistance testing for choosing an initial regimen or changing
      antiretroviral therapy, as well as possible implications of the presence or
      absence of phenotypic resistance and genotypic changes, are discussed.

PMID- 9643864
TI  - A 24-year-old woman with anorexia nervosa.

PMID- 9643865
TI  - A 42-year-old man with hypertension, 1 year later.

PMID- 9643866
TI  - A cure for the common cold? Zinc again.

PMID- 9643867
TI  - Drug-resistant HIV-1: the virus strikes back.

PMID- 9643868
TI  - New treatments for genital warts less than ideal: abstract and commentary.

PMID- 9643869
TI  - JAMA patient page: the common cold.

PMID- 9643870
TI  - Behavior of heavy metals in human urine and blood following calcium disodium
      ethylenediamine tetraacetate injection: observations in metal workers.
AB  - To evaluate the effects of calcium disodium ethylenediamine tetraacetate (CaEDTA)
      on the behavior of 8 heavy metals in human urine and blood, CaEDTA was
      administered for 1 h by intravenous injection to 18 male metal foundry workers,
      whose blood lead concentrations (PbB) were between 16 and 59 (mean 34) microg/dl.
      Significant increases were found in urinary excretion of manganese, chromium,
      lead, zinc, and copper after the start of CaEDTA injection. Urinary chromium
      excretion reached a maximal level within 1 h after the start of injection, while
      urinary manganese, lead, and zinc excretion reached their highest concentrations
      between 1 and 2 h. Urinary copper excretion reached the highest level between 2
      and 4 h. The rapid increases in urinary excretion of five metals were different
      from the "circadian rhythms," which are the normal, daily variations in renal
      glomerular filtration, reabsorption, and excretory mechanisms. Plasma lead
      concentrations were highest 1.5 h after the start of the 1-h injection, while
      plasma zinc concentration became lowest 5 h after the start of CaEDTA injection.
      Data suggest that manganese and chromium absorbed in human tissues might be
      mobilized by CaEDTA.

PMID- 9643871
TI  - Urinary excretion of arsenic metabolites after long-term oral administration of
      various arsenic compounds to rats.
AB  - The metabolism of arsenic compounds in rats was studied by comparing urinary
      metabolites of arsenic compounds administered for 1 wk or 7 mo. Male F344/DuCrj
      rats were given 100 mg As/L as monomethylarsonic acid (MMA), dimethylarsinic acid
      (DMA), trimethylarsine oxide (TMAO), or arsenobetaine (AsBe), or 10 mg As/L as
      arsenite [As(III)] via drinking water for 7 mo. Urine was collected by forced
      urination after 1 wk or 7 mo. Arsenic metabolites in urine were analyzed by ion
      chromatography with inductively coupled plasma mass spectrometry. In the case of
      As(III) ingestion, a small portion of all arsenic excreted in urine (about 6%)
      was excreted in inorganic form, while most arsenic was excreted as methylated
      arsenic metabolites. Following MMA treatments for 1 wk or 7 mo, the predominant
      products excreted were unchanged MMA and DMA accompanied by small amounts of TMAO
      and tetramethylarsonium (TeMA). In the case of DMA treatment the urinary
      compounds found were mainly the parent DMA and TMAO with minute amounts of TeMA.
      TMAO was methylated to TeMA to a slight extent after 1 wk and 7 mo of
      administration, although most TMAO was excreted in the form of unchanged TMAO.
      AsBe was predominantly eliminated in urine without any transformation. Two
      unidentified metabolites were detected in urine after 7 mo of arsenic species
      exposure; the amounts of these metabolites increased in the order DMA > MMA >
      TMAO with only small quantities of these detected in the As(III)-treated group.
      These results suggest that these unidentified metabolites are formed during a
      demethylation process, and not during methylation. Our findings indicate that
      long-term exposure to As(III), MMA, or DMA decreases the proportion of TMAO
      elimination in urine and increases that of DMA, M-1, and M-2, and that further
      methylation to TMAO to TeMA does occur to a slight extent following long-term
      exposure to arsenical compounds in rats.

PMID- 9643872
TI  - Effects of acute inhalation exposure to 1,1,1-trichloroethane on the hypothalamo
      pituitary-adrenal axis in male Sprague-Dawley rats.
AB  - 1,1,1-Trichloroethane (TRI) is a commonly used industrial solvent with a
      considerable potential for inhalation abuse. Previous studies in our laboratory
      and elsewhere have shown that this agent exerts a suppressant effect on operant
      responding, as well as a number of additional neurobehavioral effects that are
      similar to those of central nervous system (CNS) depressant drugs. In an effort
      to provide information relevant to potential mechanisms involved in the
      behavioral effects and abuse potential of TRI, the present study evaluated the
      acute effects of this agent on the activity of the hypothalamo-pituitary-adrenal
      (HPA) axis . Male Sprague-Dawley rats were exposed to 3500 or 5000 ppm TRI by
      inhalation for 10 or 30 min. Following exposure, plasma levels of
      adrenocorticotropic hormone (ACTH) and corticosterone and levels of ACTH and
      corticotropin-releasing factor (CRF) in three brain regions--hypothalamus,
      hippocampus, and frontal cortex--were determined by selective radioimmunoassays.
      Levels of TRI in the three brain regions as well as blood were measured by
      headspace gas chromatography to determine the target tissue concentrations
      responsible for neuroendocrine changes. Uptake of TRI in blood and all brain
      regions was very rapid, with stable concentrations apparently achieved within 10
      min and maintained for 30 min. During this time course, a significant decrease in
      plasma corticosterone was produced at 30 min but no significant change in plasma
      ACTH was observed with 3500 ppm TRI. However, after exposure to 5000 ppm, both
      plasma ACTH and plasma corticosterone were significantly reduced at 10 and 30
      min. ACTH levels in the three brain regions were not significantly changed by
      TRI, while hypothalamic CRF was significantly increased during exposure to 3500
      ppm. However, hypothalamic concentrations of CRF declined following 30 min at
      3500 ppm and were not significantly changed by 5000 ppm. This complexity of
      effects on the regulation of HPA axis activity likely precluded the establishment
      of consistent relationships between changes in hormonal levels and blood or
      regional brain concentrations of the inhalant. However, these actions of TRI were
      strikingly similar to those previously reported for the benzodiazepines.

PMID- 9643873
TI  - Metabolism of chloral hydrate in mice and rats after single and multiple doses.
AB  - Chloral hydrate is a hepatocarcinogen in mice but not rats. To examine this
      species-related difference, male and female B6C3F1 mice and Fischer (F344) rats
      were treated by gavage with 1 or 12 doses of chloral hydrate, and concentrations
      of the drug and its metabolites were determined in plasma at 0.25, 7, 3, 6, and
      24 h and 2, 4, 8, and 16 d after the last treatment. Maximum levels of chloral
      hydrate were observed at the initial sampling time of 0.25 h. By 1 h, levels
      dropped substantially, and by 3 h, chloral hydrate could not be detected.
      Trichloroacetic acid was the major metabolite found in the plasma, with peak
      levels being observed 1-6 h after dosing. The concentrations then slowly
      decreased such that by 2 d this metabolite could no longer be detected.
      Trichloroethanol was assayed as both the free alcohol and its glucuronide.
      Maximum levels of trichoroethanol occurred at 0.25 h, and by 1-3 h approached the
      limits of detection. A pharmacokinetic model was constructed to describe the
      metabolic data. The plasma half-life values of chloral hydrate were similar in
      both species. In mice, the rate of elimination of trichloroacetic acid was
      significantly increased after multiple doses; this difference was not observed
      with rats. The half-life of trichloroethanol and its glucuronide was
      significantly greater in rats as compared to mice. None of the metabolic
      parameters appears to account for the hepatocarcinogenicity of chloral hydrate
      seen in mice but not rats.

PMID- 9643874
TI  - Modulation of 7,12-dimethylbenz[a]anthracene disposition and hepatocarcinogenesis
      by dieldrin and chlordecone in rainbow trout.
AB  - The present study examined whether modified xenobiotic transport, resulting from
      chlordecone (CD) or dieldrin pretreatment, would alter polycyclic aromatic
      hydrocarbon (PAH) or organochlorine (OC) target organ doses and subsequent tumor
      organospecificity or incidence rates in rainbow trout. Additionally, the
      potential for exposure to dieldrin or CD, following PAH exposure, to enhance
      tumor incidence was assessed. Evaluation of CD pretreatment effects on [14C]CD
      disposition in trout was conducted following two i.p. (0-15 mg/kg) and two
      dietary (0-0.4 mg/kg/d) pretreatment regimes. To assess the influence of OC
      pretreatment on cancer induced by the PAH 7,12-dimethylbenz[a]anthracene (DMBA),
      juvenile trout were fed control, CD (0.1, 0.4 mg/kg/d), or dieldrin (0.1, 0.3
      mg/kg/d) diets for 9 wk, received a waterborne [3H]DMBA exposure (1 mg/L, 20 h),
      and resumed control, CD, or dieldrin diets for 33 wk. [3H]DMBA disposition and
      hepatic [3H]DMBA binding were examined immediately and 24 h after exposure.
      Hepatic and stomach tumor incidences were determined 33 wk after DMBA exposure.
      CD pretreatment did not influence [14C]CD or [3H]DMBA hepatic concentrations,
      hepatic [3H]DMBA DNA binding, or hepatic/stomach tumor incidence. It did,
      however, elevate bile [14C]CD and [3H]DMBA concentrations. Postinitiation
      exposure to CD weakly enhanced DMBA-induced hepatic tumor incidence at the low
      but not the high CD dose. Dieldrin pretreatment did not influence stomach
      [3H]DMBA equivalents or stomach tumor incidence but did cause an elevation in
      biliary and hepatic concentrations of [3H]DMBA equivalents. [3H]DMBA binding to
      liver DNA was significantly increased and hepatic tumor incidence was elevated by
      dieldrin pretreatment. Dieldrin treatment following DMBA initiation did not
      enhance hepatic or stomach tumor incidence. Ecoepidemiology studies, to date,
      have reported correlations between the co-occurrence of PAHs and OCs and elevated
      tumor incidence in feral fish, but cause-and-effect relationships have been
      difficult to establish. The results of the present study confirm that OCs, such
      as dieldrin and CD, play a role in modifying PAH-induced carcinogenesis in fish.

PMID- 9643875
TI  - [Reconstruction of the ossicular chain].

PMID- 9643876
TI  - Teaching caring attitudes.

PMID- 9643877
TI  - What makes a good doctor: defining the ideal end-product of medical education.

PMID- 9643878
TI  - A long-term collaborative approach to identifying future physicians.

PMID- 9643879
TI  - Caring for pregnant adolescents.

PMID- 9643880
TI  - Teaching residents about child abuse and neglect.

PMID- 9643881
TI  - Using electronic journal writing to foster reflection and provide feedback in an
      introduction to clinical medicine.

PMID- 9643882
TI  - Reinforcement of self-directed learning and the development of professional
      attitudes through peer- and self-assessment.

PMID- 9643883
TI  - Teaching professionalism through tutorial discussions of literature--stories,
      poems, and essays.

PMID- 9643884
TI  - Developing skills in promoting effective behavioral change.

PMID- 9643885
TI  - Facilitating interns' self-assessment.

PMID- 9643886
TI  - A student-planned memorial service.

PMID- 9643887
TI  - A palliative care survey to measure medical students' and health care
      professionals' knowledge and attitudes.

PMID- 9643888
TI  - Collaborative development of geriatric education modules for resident education.

PMID- 9643889
TI  - Innovation in an undergraduate geriatrics program.

PMID- 9643891
TI  - A fourth-year elective in medical education.

PMID- 9643890
TI  - Use of behavioral descriptors for performance evaluation in first- and second
      year clinical experiences.

PMID- 9643892
TI  - A first-year minicurriculum on TIA/stroke.

PMID- 9643893
TI  - Determination of third-year student exposure to and participation in learning
      objectives.

PMID- 9643894
TI  - Using patients to teach functional assessment of patients with arthritis.

PMID- 9643895
TI  - Focusing attention on critical elements of the pediatrics clerkship.

PMID- 9643896
TI  - Qualitative analysis of student-generated learning issues to assess content
      coverage in problem-based learning.

PMID- 9643897
TI  - A unit-mastery program in an ambulatory care internal medicine clerkship.

PMID- 9643898
TI  - A core anatomy program for the undergraduate medical curriculum.

PMID- 9643899
TI  - Use of structured student-facilitated small groups in a behavioral
      science/psychiatry course.

PMID- 9643900
TI  - A program to create and exchange teaching cases in radiology.

PMID- 9643901
TI  - An introduction to complementary healing practices.

PMID- 9643902
TI  - Improving communication and interviewing skills: a community-based approach.

PMID- 9643903
TI  - Teaching motivational interviewing to first-year students.

PMID- 9643904
TI  - Improving fourth-year students' complex interviewing skills.

PMID- 9643905
TI  - Group review in differential diagnosis.

PMID- 9643906
TI  - Using standardized patients to teach and learn psychotherapy.

PMID- 9643907
TI  - A crisis management program for residents in anesthesia.

PMID- 9643908
TI  - Using simulation to train residents in managing critical events.

PMID- 9643909
TI  - Flexible sigmoidoscopy training program for internal medicine residents.

PMID- 9643911
TI  - PRIME: preparing first-year medical students for an intensive clinical
      experience. The Generalist Coordinating Council.

PMID- 9643910
TI  - Case snapshots: a new tool for morning report.

PMID- 9643912
TI  - The first three days of residency: an efficient introduction to clinical
      medicine.

PMID- 9643913
TI  - The use of a virtual reality haptic device in surgical training.

PMID- 9643914
TI  - An interdisciplinary clinical performance examination for a third-year combined
      medicine-surgery clerkship.

PMID- 9643915
TI  - Global ratings versus checklist scoring in an OSCE.

PMID- 9643916
TI  - A community pediatrics/public health rotation for pediatric residents.

PMID- 9643917
TI  - Using rural training tracks to encourage rural practice careers and enhance
      training in family medicine.

PMID- 9643918
TI  - Integrating public health issues and community health care delivery.

PMID- 9643919
TI  - A fellowship in the population-centered clinical method.

PMID- 9643920
TI  - Using videoconferencing of a live surgery to teach about pelvic anatomy.

PMID- 9643921
TI  - A library-based information skills rotation for internal medicine residents.

PMID- 9643922
TI  - Teaching cross-cultural medicine and international health at home.

PMID- 9643923
TI  - Using palm-top computers to improve students' evidence-based decision making.

PMID- 9643924
TI  - Enhancing medical students' participation in the rural community.

PMID- 9643925
TI  - Shared learning between medical, dental, nursing, and therapy undergraduates.

PMID- 9643926
TI  - Learning medicine in the community.

PMID- 9643927
TI  - VA Women's Health Center as an ambulatory training site.

PMID- 9643928
TI  - Integrating technology into resident and student curricula.

PMID- 9643929
TI  - Inclusion of allied health students in a problem-based learning course.

PMID- 9643930
TI  - A multidisciplinary interclerkship on hunger and malnutrition.

PMID- 9643931
TI  - Interactive instruction technology in graduate medical education.

PMID- 9643932
TI  - Using a combined CME course to improve physicians' skills in eliciting patient
      adherence.

PMID- 9643933
TI  - Skills for internship.

PMID- 9643934
TI  - Integration of self-directed computerized patient simulations into the internal
      medicine ambulatory clerkship.

PMID- 9643935
TI  - Using standardized medical students to improve junior faculty teaching.

PMID- 9643936
TI  - A distance-learning program for telemedicine presenters.

PMID- 9643937
TI  - A certificate in medical management for physicians.

PMID- 9643938
TI  - Using a comprehensive handbook and individualized orientation plan for faculty
      development in a decentralized academic department.

PMID- 9643939
TI  - Validating a global measure of faculty teaching performance.

PMID- 9643940
TI  - Promoting small-group teaching through funding changes.

PMID- 9643941
TI  - General Clinical Research Center Scholars Program.

PMID- 9643942
TI  - Using videoconferencing to train community family medicine preceptors.

PMID- 9643943
TI  - Integrating information technology training into an established faculty
      development program.

PMID- 9643944
TI  - A teaching skills workshop for community preceptors.

PMID- 9643945
TI  - An intramural grants program for developing medical school curricula.

PMID- 9643946
TI  - Challenges in the Study of Encephalomyopathies of Mitochondrial Origin.
      Proceedings of a conference. Philadelphia, Pennsylvania, USA. 4-7 April 1997.

PMID- 9643947
TI  - Methods development for epidemiologic investigations of the health effects of
      prolonged ozone exposure. Part II. An approach to retrospective estimation of
      lifetime ozone exposure using a questionnaire and ambient monitoring data
      (California sites).
AB  - An extensive body of data supports a relation between acute exposures to ambient
      ozone and the occurrence of various acute respiratory symptoms and changes in
      measures of lung function. In contrast, relatively few data are available on the
      human health effects that result from long-term exposure to ambient ozone,
      Current efforts to study long-term ozone-related health effects are limited by
      the methods available for ascertaining lifetime exposures to ozone. The present
      feasibility study was undertaken as part of the Health Effects Institute's
      Environmental Epidemiology Planning Project (Health Effects Institute 1994) to
      (1) determine whether, in the context of an epidemiologic study, reliable
      estimates can be obtained for lifetime exposures to ozone by combining estimates
      from lifetime residential histories, typical activity patterns during life, and
      residence-specific ambient ozone monitoring data; (2) identify the minimum data
      required to produce reliable estimates of lifetime exposure; and (3) analyze the
      relations between various estimates of lifetime ozone exposure and measures of
      lung function. A convenience sample of 175 first-year students at the University
      of California, Berkeley, who lived all of their lives in selected areas of
      California (the Los Angeles Basin or the San Francisco Bay Area), were studied on
      two occasions (test and retest or test sessions 1 and 2), five to seven days
      apart. Residential and lifestyle data were obtained from a questionnaire:
      residence-based ambient ozone exposure values were assigned by interpolation of
      ambient ozone monitoring data to residential locations. Estimated lifetime
      exposure was based on average ozone levels between 10 a.m. and 6 p.m. and hours
      of exposure to ozone concentrations greater than 60 parts per billion (ppb).
      "Effective" lifetime exposure to ozone was based on a weighted average of
      estimated time spent in different ambient ozone environments as determined by
      different combinations of activity data. Pulmonary function was evaluated with
      flows and volumes from maximum expiratory flow-volume curves and slope of phase
      III of the single-breath nitrogen washout (SBNW) curves. Although the test-retest
      reliability of the residential history was acceptably high only for first and
      second residences, most of the unreliability for other residences came from
      residences occupied for relatively short durations. Therefore, the test-retest
      reliability of estimated lifetime exposure to ozone was high, with intraclass
      correlations greater than 0.90 for all approaches evaluated. Multiple, linear
      regression analyses showed a consistently negative relation between estimates of
      lifetime exposure to ozone and flows that reflect the physiology of pulmonary
      small airways. No relation was observed between lifetime ozone exposure and
      forced expiratory volume or the slope of phase III, and the relation between
      lifetime exposure and forced expiratory volume in one second was inconsistent.
      The results of the flow measures were unaffected by the method used to estimate
      lifetime exposure and gave effect estimates that were nearly identical. The data
      from this study indicate that useful and reproducible estimates of lifetime ozone
      exposure can be obtained in epidemiologic studies by using a residential history.
      However, the total burden of ozone to which the subjects were exposed cannot be
      determined accurately from such data. Nonetheless, the estimates so obtained
      appear to be associated with alterations in pulmonary function that are
      consistent with the predicted site of maximum effect of ozone in the human lung.

PMID- 9643948
TI  - Methods development for epidemiologic investigations of the health effects of
      prolonged ozone exposure. Part III. An approach to retrospective estimation of
      lifetime ozone exposure using a questionnaire and ambient monitoring data (U.S.
      sites).
AB  - Methods are needed for retrospective estimation of long-term ozone exposures in
      epidemiologic studies. The overall objective of this study was to evaluate
      whether data from available U.S. ozone monitoring sites are useful for estimating
      lifetime ozone exposures of young adults (for example, college students). Several
      aspects of this question were evaluated. First, we applied and (compared several
      spatial interpolation methods to a set of long-term average ozone data from all
      U.S. monitoring sites in operation from 1981 through 1990. Interpolation methods
      included simple and weighted averages, linear regression, and, in an exploratory
      way, kriging. The comparison of methods was carried out for five different
      metrics of ozone concentration: the daily one-hour maximum (MAX1) and eight-hour
      maximum (MAX8), the average ozone concentrations between 10 a.m. and 6 p.m.
      (MID8) and between 10 a.m. and 10 p.m. (MID12), and the sum of all hourly ozone
      concentrations greater than or equal to 60 parts per billion (ppb) (SUM06). We
      also tested whether interpolations were improved by modeling the influence of
      covariates such as population density, elevation, and weather on ozone
      concentrations. We analyzed the reliability of a set of newly developed questions
      about past activity levels among a group of 52 freshmen students at Yale
      University. This was done by analyzing the agreement between answers to the same
      questionnaire administered two times, one month apart (test and retest), to the
      same students. Finally, we combined the interpolation models with residential
      history information obtained by questionnaire to derive long-term ozone exposure
      estimates for a group of 200 Yale freshmen. Results of our study showed that the
      density of available monitoring sites appears to be adequate for estimating
      spatial patterns of long-term average ambient ozone concentrations. A simple
      regression-based interpolation on the three nearest sites produced consistently
      good results. Including covariates in the interpolation models did not
      substantially improve the estimates. The largest estimation errors occurred for
      areas where ozone concentrations were highest. The newly developed activity
      history questions exhibited fair to moderate reliability, The results of this
      work imply that reasonably precise estimates of long-term ambient ozone
      concentrations for use in large-scale epidemiologic studies can be achieved by
      interpolating ozone concentrations between available U.S. monitoring sites. This
      study did not address the issues of whether and how retrospective data on factors
      that modify exposure or dose (e.g., indoor/outdoor penetration of ozone and time
      outdoors) can be used to derive estimates of long-term personal ozone exposures
      and contribute to the assessment of received dose.

PMID- 9643950
TI  - Sebaceous gland, acne and related disorders--an epilogue.

PMID- 9643951
TI  - Sebaceous gland, acne and related disorders. basic and clinical research,
      clinical entities and treatment. Proceedings of the 4th International Dermatology
      Symposium. Berlin, April 11-13, 1997.

PMID- 9643949
TI  - Wanderlust kinetics and variable Ca(2+)-sensitivity of dSlo [correction of
      Drosophila], a large conductance CA(2+)-activated K+ channel, expressed in
      oocytes.
AB  - Cloned large conductance Ca2+-activated K+ channels (BK or maxi-K+ channels) from
      Drosophila (dSlo) were expressed in Xenopus oocytes and studied in excised
      membrane patches with the patch-clamp technique. Both a natural variant and a
      mutant that eliminated a putative cyclic AMP-dependent protein kinase
      phosphorylation site exhibited large, slow fluctuations in open probability with
      time. These fluctuations, termed "wanderlust kinetics," occurred with a time
      course of tens of seconds to minutes and had kinetic properties inconsistent with
      simple gating models. Wanderlust kinetics was still observed in the presence of
      5mM caffeine or 50 nM thapsigargin, or when the Ca2+ buffering capacity of the
      solution was increased by the addition of 5 mM HEDTA, suggesting that the
      wanderlust kinetics did not arise from Ca2+ release from caffeine and
      thapsigargin sensitive internal stores in the excised patch. The slow changes in
      kinetics associated with wanderlust kinetics could be generated with a discrete
      state Markov model with transitions among three or more kinetic modes with
      different levels of open probability. To average out the wanderlust kinetics,
      large amounts of data were analyzed and demonstrated up to a threefold difference
      in the [Ca2+]i required for an open probability of 0.5 among channels expressed
      from the same injected mRNA. These findings indicate that cloned dSlo channels in
      excised patches from Xenopus oocytes can exhibit large variability in gating
      properties, both within a single channel and among channels.

PMID- 9643952
TI  - Organ transplantation from donor who died of cyanide poisoning: a case report.
AB  - Shortage of donor organs has become on of the most important limiting factors in
      the field of transplantation. Suitability of organs from patients dying from
      poisoning is an unexplored area. This is because of the suspicion that the
      organs, in particular the liver and the kidneys, might have been irreversibly
      damaged by the poison. We report a case of cyanide poisoning in which the kidneys
      and corneas were harvested after the level of poison fell to below lethal
      concentration. These organs were later transplanted without any evidence of
      adverse effects at follow-up.

PMID- 9643953
TI  - Polarity of meiotic recombination in the bronze locus of maize.

PMID- 9643954
TI  - Israel bans import of sildenafil citrate after six deaths in the US.

PMID- 9643955
TI  - Prostate cancer screening reduces deaths.

PMID- 9643956
TI  - Are sex and death related? Study did not treat sexual behaviour with the
      importance it deserves.

PMID- 9643957
TI  - Cancer in the offspring of radiation workers. Exposure to internal radioisotopes
      may be responsible.

PMID- 9643958
TI  - Cancer in the offspring of radiation workers. Combination of antibiotics and non
      fatal infections may be responsible for higher number of deaths from leukemia.

PMID- 9643959
TI  - Cognitive impairment and survival in very elderly people. Decreased survival with
      cognitive impairment seems not be related to comorbidity.

PMID- 9643960
TI  - Effect of moderate alcohol consumption on Lp(a) lipoprotein concentrations. No
      effect seen in Australian drinkers.

PMID- 9643961
TI  - Effect of moderate alcohol consumption on Lp(a) lipoprotein concentrations.
      Reduction is not found in women.

PMID- 9643962
TI  - Interventions to treat shoulder pain. Lack of concordance between rheumatologists
      may render multicentre studies invalid.

PMID- 9643964
TI  - Proceedings of the International Ion Chromatography Symposium 1997. Santa Clara,
      California, USA. 14-17 September 1997.

PMID- 9643963
TI  - IBC Conference on Engineered Animal Models: Advances and Applications,
      Washington, DC, USA, 22-23 September 1997.

PMID- 9643965
TI  - Duplicate publication.

PMID- 9643966
TI  - The effect of suspending solution supplemented with marine cations on the
      oxidation of Biolog GN MicroPlate substrates by Vibrionaceae bacteria.
AB  - Bacteria belonging to the family Vibrionaceae were suspended using saline and a
      solution prepared from a marine-cations supplement. The effect of this on the
      profile of oxidized substrates obtained when using Biolog GN MicroPlates was
      investigated. Thirty-nine species belonging to the genera Aeromonas, Listonella,
      Photobacterium, and Vibrio were studied. Of the strains studied, species of
      Listonella, Photobacterium, and Vibrio could be expected to benefit from a marine
      cations supplement that contained Na+, K+, and Mg2+. Bacteria that are not of
      marine origin are usually suspended in normal saline. Of the 39 species examined,
      9 were not included in the Biolog data base and were not identified. Of the 30
      remaining species, 50% were identified correctly using either of the suspending
      solutions. A further 20% were correctly identified only when suspended in saline.
      Three species, or 10%, were correctly identified only after suspension in the
      marine-cations supplemented solution. The remaining 20% of species were not
      correctly identified by either method. Generally, more substrates were oxidized
      when the bacteria had been suspended in the more complex salts solution. Usually,
      when identifications were incorrect, the use of the marine-cations supplemented
      suspending solution had resulted in many more substrates being oxidized. Based on
      these results, it would be preferable to use saline to suspend the cells when
      using Biolog for identification of species of Vibrionaceae. A salts solution
      containing a marine-cations supplement would be preferable for environmental
      studies where the objective is to determine profiles of substrates that the
      bacteria have the potential to oxidize. If identifications are done using marine
      cations supplemented suspending solution, it would be advisable to include
      reference cultures to determine the effect of the supplement. Of the Vibrio and
      Listonella species associated with human clinical specimens, 8 out of the 11
      studied were identified correctly when either of the suspending solutions was
      used.

PMID- 9643967
TI  - Retraction: An endo-beta-1,4-glucanase gene (celA) from the rumen anaerobe
      Ruminococcus albus 8: cloning, sequencing, and transcriptional analysis.

PMID- 9643968
TI  - Rapid method for the detection of genetically engineered microorganisms by
      polymerase chain reaction from soil and sediments.
AB  - A rapid and sensitive method for the detection of genetically engineered
      microorganisms in soil and sediments has been devised by in vitro amplification
      of the target DNAs by a polymerase chain reaction. A cloned catechol 2,3
      dioxygenase gene located on the recombinant plasmid pOH101 was transferred to
      Pseudomonas putida MMB2442 by triparental crossing and used as a target organism.
      For the polymerase chain reaction from soil and sediment samples, the template
      DNA was released from a 100-mg soil sample. Bacterial seeded soil samples were
      washed with Tris-EDTA buffer (pH 8.0) and treated with a detergent lysis solution
      at 100 degrees C. After addition of 1% polyvinylpolypyrrolidine solution, the
      samples were boiled for 5 min. Supernatant containing nucleic acid was purified
      with a PCR purification kit. The purified DNA was subjected to polymerase chain
      reaction, using two specific primers designed for the amplification of catechol
      2,3-dioxygenase gene sequences. The detection limit was 10(2) cells per gram of
      soil. This method is rapid and obviates the need for lengthy DNA purification
      from soil samples.

PMID- 9643969
TI  - UCSD Mitochondrial Medicine Conference. San Diego, California, USA. February 19
      21, 1998.

PMID- 9643970
TI  - Tumor hypoxia: the role of nuclear medicine.

PMID- 9643971
TI  - Radiation doses deriving from patients undergoing 111In-DTPA-D-Phe-1-octreotide
      scintigraphy.

PMID- 9643972
TI  - Radiation dose to technicians for nuclear medicine procedures.

PMID- 9643973
TI  - Dose contribution from iron-55 as a daughter radionuclide of cobalt-55.

PMID- 9643974
TI  - Cardiac dysfunction in cancer patients receiving paclitaxel.

PMID- 9643975
TI  - Chemotherapy and uptake of technetium-99m sestamibi in breast cancer.

PMID- 9643976
TI  - Modulation of the Immune Response to Vaccine Antigens. Proceedings of a
      conference. Bergen, Norway, June 18-21, 1996.

PMID- 9643977
TI  - Amplification of the translocated c-myc genes in three Burkitt lymphoma cell
      lines.
AB  - Translocations of the coding exons of the human c-myc gene are consistent
      features of human Burkitt lymphomas (BL). In the BL cell lines CA46, JD40, and
      ST486, the second and third c-myc exons have been translocated into the
      immunoglobulin heavy chain locus. In addition to this rearrangement, in all three
      cell lines, we have found that the translocated c-myc exons show low-level
      amplification relative to restriction fragments from the germ-line c-myc gene.
      The patterns of hybridization of an IgM switch region probe suggest that
      immunoglobulin heavy chain sequences have been co-amplified with the translocated
      c-myc sequences. Differential sedimentation was used to determine whether the
      amplified sequences reside in high-molecular-weight chromosomes or low-molecular
      weight extrachromosomal DNA. In JD40 and ST486 cells, the amplified c-myc
      sequences were found on high-molecular-weight chromosomes ST486 cells also
      contained translocated C-myc sequences in low-molecular-weight, extrachromosomal
      DNA, as did CA46 cells. These conclusions were corroborated by fluorescence in
      situ hybridization (FISH) of HeLa, CA46, ST486 and JD40 metaphase chromosomes.
      These results suggest that there is ongoing selection for cells containing
      amplified copies of the expressed c-myc sequences. and that there is continuous
      generation of extrachromosomal copies of the translocated c-myc sequences in
      ST486 and CA46 cells.

PMID- 9643978
TI  - Properties of exgS, a gene for a major subunit of the Clostridium cellulovorans
      cellulosome.
AB  - The nucleotide sequence of P70, one of the three major subunits of the
      Clostridium cellulovorans cellulosome, has been determined. The gene designated
      as exgS (Genbank Accession No. U34793) consists of 2112 bp and encodes a protein
      containing 703 amino acids with a molecular mass of 77.7 kDa. ExgS has a putative
      signal peptide sequence of 32 amino acids. The N-terminal region is separated
      from the C-terminal region by a short-Pro-Thr-Pro linker. The C-terminal region
      of ExgS contains a duplicated sequence (DS), each sequence consisting of 22 amino
      acids. exgS, located 67 bp downstream of cbpA in the chromosome, is immediately
      upstream of a gene encoding a family 9 type endoglucanase that we have designated
      as EngH. This gene cluster to date consists of regA-cbpA-exgS-engH. Recombinant
      ExgS (rExgS) containing no signal peptide was expressed in E. coli. The rExgS
      actively digested several forms of cellulose, including Avicel, Sigmacell101,
      crystalline cellulose, and xylan, but not carboxymethyl cellulose (CMC).
      Cellotetraose was the smallest oligosaccharide substrate for rExgS. The enzymatic
      studies indicated that ExgS was an exoglucanase and had some properties similar
      to that of CelS from C. thermocellum and CelF from C.cellulolyticum. An
      exoglucanase has now been found to be a component of the C. cellulovorans
      cellulosome as well as the previously reported endoglucanases.

PMID- 9643979
TI  - [Retrospective analysis of the relationship between HUS incidence and antibiotics
      among patients with Escherichia coli O157 enterocolitis in the Sakai outbreak].
AB  - An outbreak of Escherichia coli O157:H7 infection occurred in July 1996 in Sakai
      City. About 5000 children were infected, 122 of whom developed hemolytic uremic
      syndrome (HUS). In this outbreak, almost all patients were administrated some
      type of antibiotics. The effects of antibiotics on E. coli O157 associated
      hemorrhagic colitis (HC) have been controversial. In this study, we focused on
      the effects of antibiotics on development of HUS in the HUS in the Sakai
      outbreak. We retrospectively determined the antibiotics administrated within
      three days after the onset of HC, clinical courses, and laboratory data of 301
      patients who were hospitalized and identified as Escherichia coli O157 infection
      by stool culture, from results of questionnaires sent by the Osaka Prefecture
      Medical Association to hospitals in Osaka Prefecture. The antibiotics used could
      be identified for 216 patients. The incidence of HUS among these patients was
      11.6%. They were divided into 19 groups based on the type of antibiotics
      administrated. The incidence of HUS in the new quinolone (3.7%) group was low,
      but was high in the intravenous cephalosporin (18.2%) group. The differences in
      the incidence of HUS among the 19 antibiotic groups was significant (p < 0.05) on
      analysis of covariance which eliminated the contributions of variables including
      age, sex and laboratory data. These findings indicate that the suitable
      antibiotics can prevent the development of E. coli O157-associated HUS.

PMID- 9643980
TI  - [Myelodysplastic syndrome and cancer].

PMID- 9643981
TI  - The Trypanosome Surface. Proceedings of the Francqui Colloquium on the Expression
      and Function of Surface Proteins in Trypanosoma Brucei. Brussels, May 1997.

PMID- 9643983
TI  - "The slow code".

PMID- 9643982
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 20-1998. A 53-year-old man with cardiac amyloidosis and a left
      pulmonary mass.

PMID- 9643984
TI  - "The slow code".

PMID- 9643985
TI  - "The slow code".

PMID- 9643986
TI  - "The slow code".

PMID- 9643987
TI  - "The slow code".

PMID- 9643988
TI  - "The slow code".

PMID- 9643989
TI  - Treatment of paraphilia with an analogue of gonadotropin-releasing hormone.

PMID- 9643990
TI  - Treatment of paraphilia with an analogue of gonadotropin-releasing hormone.

PMID- 9643991
TI  - Preemptive liver transplantation from a living related donor for primary
      hyperoxaluria type I.

PMID- 9643992
TI  - The response of early gastric cancer to proton-pump inhibitors.

PMID- 9643993
TI  - Case 5-1998: bone marrow blasts in chronic myelomonocytic leukemia.

PMID- 9643994
TI  - Clinical problem-solving: a square peg in a round hole.

PMID- 9643995
TI  - Clinical problem-solving: a square peg in a round hole.

PMID- 9643996
TI  - Clinical problem-solving: a square peg in a round hole.

PMID- 9643997
TI  - Clinical problem-solving: a square peg in a round hole.

PMID- 9643998
TI  - Ephedrine is not phenylephrine.

PMID- 9644000
TI  - [AIDS epidemic in Kaliningrad].

PMID- 9643999
TI  - More on varicella immunization.

PMID- 9644001
TI  - [Older women with AIDS].

PMID- 9644002
TI  - [Discontinuation of Act Up!].

PMID- 9644003
TI  - [Placebos as AIDS therapy, continued].

PMID- 9644004
TI  - [Live attenuated AIDS vaccine possibly lethal].

PMID- 9644005
TI  - [Anglo-Saxon guidelines for the treatment of community-acquired pneumonia also
      applicable in The Netherlands].

PMID- 9644006
TI  - Being heard.

PMID- 9644007
TI  - Trading places.

PMID- 9644008
TI  - UV-DNA damage in mouse and human cells induces the expression of tumor necrosis
      factor alpha.
AB  - Ultraviolet light induces the expression of tumor necrosis factor alpha (TNF
      alpha) in many mammalian cells. We have examined the signal for this induction in
      a human DNA repair-deficient cell line carrying a transgene composed of the
      murine TNF regulatory sequences fused to the chloramphenicol acetyltransferase
      (CAT) structural gene. When compared by fluence, UVC was a more efficient inducer
      of CAT than was UVB, but they were equivalent inducers when compared by the
      frequency of cyclobutyl pyrimidine dimers produced by each source. Further,
      treatment of UV-irradiated cells with the prokaryotic DNA repair enzyme T4
      endonuclease V increased the level of repair of dimers and concomitantly reduced
      CAT gene expression. Membrane-bound TNF alpha expression was increased by UV and
      reduced by repair of dimers. Finally, in the TNFcat transgene system, DNA damage
      directly to the cell with the transgene was required as cocultivation of
      unirradiated TNFcat cells with UV-irradiated cells did not increase CAT activity.
      These results show that DNA damage is a signal for the induction of TNF alpha
      gene expression in mouse and human cells.

PMID- 9644009
TI  - Culturing new life.

PMID- 9644010
TI  - The prevention pill.

PMID- 9644011
TI  - Alcohol in the western world.

PMID- 9644012
TI  - It's not rocket science--but it can save lives.

PMID- 9644013
TI  - NIH plans bioengineering initiative.

PMID- 9644014
TI  - New rules on human subjects could end debate in Canada.

PMID- 9644015
TI  - Tau protein mutations confirmed as neuron killers.

PMID- 9644016
TI  - Old, old skull has a new look.

PMID- 9644017
TI  - One-eyed animals implicate cholesterol in development.

PMID- 9644018
TI  - Shotgun sequencing of the human genome.

PMID- 9644019
TI  - Deuteronomy?: a puzzle of deuterium and oxygen on Mars.

PMID- 9644020
TI  - Glutamate receptor activation: a four-step program.

PMID- 9644022
TI  - Proceedings of the University of Colorado Cancer Center Conference: Recent
      Developments and Future Directions in the Research and Management of Anorexia and
      Cachexia. Cancun, Mexico, October 23-25, 1997.

PMID- 9644021
TI  - Circadian rhythms. An end in the beginning.

PMID- 9644023
TI  - Annual Congress of the Neurology Association of South Africa. Rustenburg, North
      West, 11-14 March 1998. Abstracts.

PMID- 9644024
TI  - [Salmonella dublin in cattle].

PMID- 9644025
TI  - [In certain publications, the main author, A. Jendryczko is suspected of
      plagiarism].

PMID- 9644026
TI  - [In response to correspondence from 27.12.1997, the editors are informed that the
      article in question was based on collected material from the Gynecologic Clinic
      II in the years 1990-1991].

PMID- 9644027
TI  - [In this situation, my opinion concerning the identification of an article which
      I co-authored as plagiarism is that it is wrong and groundless].

PMID- 9644028
TI  - [My explanation concerning the situation regarding articles identified as
      plagiarism].

PMID- 9644030
TI  - Fever of unknown origin and anemia with Rhodococcus equi infection in an
      immunocompetent patient.

PMID- 9644029
TI  - Male infertility and the genetics of spermatogenesis.

PMID- 9644031
TI  - Gelatinase B modulates selective opening of the blood-brain barrier during
      inflammation.
AB  - Matrix metalloproteinases (MMPs) are associated with neuroinflammatory diseases,
      and blood-brain barrier damage is a pathophysiological consequence of central
      nervous system inflammation. We examined whether an increase in MMP production is
      coupled with the breakdown of blood-brain barrier integrity in the
      lipopolysaccharide (LPS)-injured brain. Rat brain stimulated with LPS showed a
      significant rise in gelatinase B (MMP-9) production at 24 h compared with either
      tumor necrosis factor-alpha (TNF-alpha) or saline-injected controls. Latent 92
      kDa gelatinase B was detected by 4 h, peaked at 8 h, and persisted for 24 h after
      LPS injection. Production of the active 84-kDa form of gelatinase B was less
      pronounced, but paralleled 92-kDa enzyme expression. Breakdown in blood-brain
      barrier integrity, measured by the infiltration of radiolabeled exogenous markers
      into the brain, was significant to [14C]sucrose (molecular mass 342 Da) and
      injected animals compared with saline-injected controls. The extent of MMP
      involvement in barrier permeability was examined in animals treated with the MMP
      inhibitor BB-1101. A significant drop in gelatinase A and B production was
      detected in LPS-injured animals receiving BB-1101 compared with untreated
      animals. This MMP inhibitor also reduced [14C]sucrose uptake in LPS-injected
      animals, but had no effect on [14C]dextran uptake. MMP production is upregulated
      in LPS-injured brain tissue and is instrumental in regulating the size
      differentiated opening of the blood-brain barrier during acute neuroinflammation.

PMID- 9644032
TI  - Mechanisms of the antidiabetic effects of the beta 3-adrenergic agonist CL-316243
      in obese Zucker-ZDF rats.
AB  - Previous studies have demonstrated that chronic cold exposure activates the
      sympathetic nervous system, increases energy expenditure, improves glucose uptake
      in peripheral tissues [brown and white adipose tissues (BAT and WAT) and muscles]
      of normal rats. The goal of the present studies was to test whether the selective
      beta 3-adrenergic agonist CL-316243 (CL) would mimic the beneficial beneficial
      effects of cold exposure in lean and obese ZDF/Gmi-fa male (ZDF) rats, a new
      model of type II diabetes. In obese ZDF rats, chronic infusion of CL (1 mg.kg
      1.day-1 for 14 days) significantly decreased body weight gain, food intake, and
      WAT weight. It also increased total tissue cytochrome oxidase activity, not only
      in BAT (15 times), but also in WAT (2-4) times, suggesting that it progressively
      enhanced mitochondriogenesis in adipose tissues. CL treatment normalized
      hyperglycemia and reduced hyperinsulinemia and circulating free fatty acid (FFA)
      levels. It also improved glucose tolerance and reduced insulin response during an
      intravenous glucose tolerance test. In general, the beneficial effects of CL were
      more pronounced in obese than in lean rats. Hyperinsulinemic-euglycemic glucose
      clamps combined with the [2-3H]deoxyglucose method revealed that CL markedly
      improved insulin responsiveness in obese rats (3-4 times) and increased glucose
      uptake in BAT (21 times), WAT (3 times), skeletal muscles (2-3 times), and in the
      diaphragm (2.8 times), but not in the heart. It is concluded that chronic CL
      treatment improves glucose tolerance and insulin responsiveness in obese ZDF rats
      by a mechanism similar to that induced by chronic cold exposure, i.e., by
      stimulating facultative thermaogenesis, mitochondriogenesis, and glucose
      utilization in BAT and WAT. In addition to this mechanism, the reduction in
      plasma FFA levels induced by chronic CL treatment may further contribute to
      enhance glucose uptake in skeletal muscles (a tissue that does not express
      typical beta 3-adrenoceptors) via the "glucose-fatty acid" cycle. The antiobesity
      and antidiabetic properties of CL suggest that selective beta 3-adrenergic
      agonists may represent useful agents for the treatment of type II diabetes.

PMID- 9644033
TI  - Rat trehalase: cDNA cloning and mRNA expression in adult rat tissues and during
      intestinal ontogeny.
AB  - A partial rat trehalase cDNA has been cloned and used to examine trehalase mRNA
      expression. Northern blotting with total RNA from 11 adult rat tissues showed a
      trehalase transcript only in small intestine, where it was abundant in proximal
      regions but declined steeply toward the ileum. During development, trehalase mRNA
      was not detectable in jejunum until postnatal day 19 and then increased markedly
      through day 25. Modest levels in trehalase mRNA were induced precociously by
      administration of dexamethasone, with increasing responsiveness evident between
      the first and second postnatal weeks. In contrast, analysis of sucrase-isomaltase
      mRNA on the same blots showed maximal induction at both ages. In adrenalectomized
      animals, the ontogenic increase of trehalase mRNA began as usual but proceeded
      more slowly than in control animals. Overall, trehalase mRNA expression in the
      rat displayed both similarities and differences compared with rabbit. Moreover,
      the differences revealed in glucocorticoid responsiveness of trehalase mRNA and
      sucrase-isomaltase mRNA suggest that the actions of these hormones on the
      developing intestine may be more complex than previously recognized.

PMID- 9644034
TI  - Effect of renal interstitial adenosine infusion on phosphate excretion in
      diabetes mellitus rats.
AB  - We previously demonstrated an increased sensitivity of the renal vasculature to
      adenosine (ADO) mediated via ADO A1 receptors in streptozotocin (STZ) diabetic
      rats. Because ADO stimulates P(i) reabsorption in the proximal tubule, the
      present study was performed to determine whether the sensitivity of the renal
      tubular system to the antiphosphaturic effect of ADO is enhanced in STZ rats.
      Clearance studies were performed, and ADO was infused into the renal interstitium
      via implanted matrices in STZ- and control (Con) rats to mimic the effects of
      endogenous ADO. Renal phosphate excretion was significantly increased in STZ rats
      (0.75 +/- 0.05 mumol/24 h) compared with Con rats (0.35 +/- 0.08 mumol/24 h), and
      fractional phosphate excretion (FEPi) tended to be higher in STZ rats (34.8 +/-
      4.1%) than in Con rats (26.7 +/- 2.2%). Renal interstitial ADO infusion (5
      mumol/h) was significantly more antiphosphaturic in STZ rats (FEPi decreased by
      2.90 +/- 1.6%; P > 0.05), in which ADO only tended to decrease FEPi. To determine
      the role of ADO A1 receptors on P(i) excretion, the selective ADO A1 receptor
      blocker 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) was infused into the renal
      interstitium. DPCPX increased FEPi by 4.3 +/- 1.2% (P < 0.05) in the presence and
      7.1 +/- 3.9% (P < 0.05) in the absence of ADO infusion in Con rats but had no
      effect on FEPi in STZ rats. In conclusion, STZ-diabetes mellitus enhances the
      antiphosphaturic effect of ADO by mechanisms unrelated to ADO A1 receptor
      stimulation.

PMID- 9644035
TI  - Duodenal nutrient exposure elicits nutrient-specific gut motility and vagal
      afferent signals in rat.
AB  - Volume and chemical characteristics of meals in the gut have been proposed to
      generate vagal afferent signals that mediate the negative feedback control of
      ingestion and gastric emptying. Furthermore, duodenal nutrients elicit changes in
      gastrointestinal motility that may stimulate mechanosensitive vagal afferents.
      The degree to which the activity of an individual vagal afferent fiber can be
      modified by moth mechanical and nutrient properties in the gut remains unclear.
      The present studies evaluated the relationships between distal antral and
      proximal duodenal load-sensitive vagal afferent activity and gastroduodenal
      motility in response to duodenal nutrient exposure in ketamine-xylazine
      anesthetized rats. Duodenal carbohydrate (glucose) and amino acid (peptone)
      infusions (0.2 ml/min, 0.2-0.5 kcal/ml) stimulated concentration-dependent
      increases in 1) antroduodenal contractions and 2) antral and duodenal vagal
      afferent activity beyond those attributable to osmolarity alone. In addition,
      duodenal peptone was more effective than equicaloric glucose in eliciting this
      vagal activity. These data demonstrate that the proximal duodenum can
      discriminate its nutrient chemical contents and that gastroduodenal load
      sensitive vagal afferents indirectly transduce nutrient chemical information.

PMID- 9644036
TI  - Splanchnic and vagal denervation attenuate central Fos but not AVP responses to
      intragastric salt in rats.
AB  - We have recently reported that an acute intragastric hypertonic saline load
      increases plasma arginine vasopressin (PAVP) and Fos immunoreactivity in several
      central nuclei, including the supraoptic nucleus (SON), paraventricular nucleus
      (PVN), nucleus of the solitary tract (NTS), area postrema (AP), and lateral
      parabrachial nucleus (LPBN). We hypothesized that these responses are mediated by
      stimulation of peripheral osmoreceptors with splanchnic and/or vagal afferent
      projections. To test this hypothesis, we examined the effect of bilateral
      subdiaphragmatic vagotomy and bilateral splanchnic denervation on the PAVP and
      Fos immunoreactivity responses to intragastric hypertonic saline infusion in
      awake rats. Compared with responses in sham rats, Fos immunoreactivity responses
      were significantly reduced in vagotomized rats in the AP, SON, and PVN, whereas
      normal Fos levels were observed in the LPBN. However, vagotomized rats exhibited
      a normal increase in PAVP. Splanchnic-denervated rats also exhibited similar
      changes in PAVP in response to intragastric hypertonic saline compared with sham
      denervated rats, and no differences were observed in Fos immunoreactivity in the
      LPBN, SON, and PVN compared with sham rats. However, splanchnic-denervated rats
      were observed to have significantly lower Fos staining in the NTS and AP compared
      with sham rats. The inability of splanchnic or vagal denervation alone to block
      the PAVP response to intragastric hypertonic saline suggests that either
      peripheral osmoreceptors project via both splanchnic and vagal afferents to
      mediate AVP release or that the observed response of PAVP is due to the
      activation of central osmoreceptors in the absence of measurable changes in
      plasma osmolality.

PMID- 9644037
TI  - Insulin increases fatty acid synthase gene transcription in human adipocytes.
AB  - The purpose of this study was to investigate the molecular mechanism whereby
      insulin increases expression of a key de novo lipogenic gene, fatty acid synthase
      (FAS), in cultured human adipocytes and hepatoma cells. RNA isolated from
      cultured adipocytes or from Hep G2 cells treated with or without insulin (20 nM)
      was analyzed. In addition, run-on transcription assays and measurements of RNA
      half-life were performed to determine the controlled step in FAS gene regulation
      by insulin. We demonstrated that FAS mRNA was expressed in both Hep G2 cells and
      human adipocytes. Insulin induced an approximately five- and three-fold increase
      in FAS mRNA content in adipocytes and hepatoma cells, respectively. Similar
      regulation of FAS was observed in adipocytes from lean and obese human subjects.
      Furthermore, we demonstrated that the induction of human FAS expression by
      insulin was due to increased transcription rate of the FAS gene in human
      adipocytes, whereas mRNA stabilization accounted for increased FAS mRNA content
      in hepatoma cells. In conclusion, we report here for the first time expression of
      human FAS mRNA and its specific transcriptional induction by insulin in cultured
      human adipocytes.

PMID- 9644038
TI  - Changes in extracellular serotonin in rat hypothalamus affect thermoregulatory
      function.
AB  - Experiments were carried out to determine the effects of altering the serotonin
      (5-HT) levels in the hypothalamus on thermoregulatory function in unanesthetized
      restrained rats. Local perfusion of the hypothalamus with dialysis solution
      containing 5-hydroxytryptophan (a 5-HT precursor), fluoxetine (a 5-HT reuptake
      inhibitor), or high potassium significantly increased both colonic temperature
      (Tco) and the extracellular concentrations of 5-HT in the hypothalamus.
      Reciprocally, both extracellular concentration of 5-HT in the hypothalamus and
      Tco were decreased with a dialysis solution containing tetrodotoxin (which blocks
      the voltage-dependent sodium channel), zero calcium concentration, or systemic
      administration of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT,5-HT1A
      agonist). Intrahypothalamic administration of 8-OH-DPAT and (2,5-dimethoxy-4
      iodophenyl)-2-aminopropane (a 5-HT2 agonist) produced hypothermic and
      hyperthermic effects, respectively. The results indicate that elevating the 5-HT
      levels in the hypothalamus activates postsynaptic 5-HT2 receptors and results in
      hyperthermic effects, whereas stimulation of presynaptic 5-HT1A receptors in the
      hypothalamus reduces the endogenous 5-HT release and results in hypothermic
      effects.

PMID- 9644039
TI  - Delayed vagal withdrawal slows circulatory but not oxygen uptake responses at
      work increase.
AB  - The effect of delayed vagal activity withdrawal on cardiorespiratory responses at
      an increase in workload was examined. Eleven volunteers (21 +/- 3 yr, 66 +/- 4
      kg) performed cycle ergometer exercise at a work rate corresponding to 80% of
      ventilatory threshold after 3 min of unloaded cycling. Facial stimulation was
      given by applying a vinyl bag filled with cold water (3-5 degrees C) to the face
      1 min before to 1 min after the increase in workload (S2 trial) or no stimulation
      was given (Nr trial). Oxygen uptake (VO2), heart rate (HR), and cardiac output
      (Q) were continuously recorded in four transitions for each trial. Data were
      averaged for each subject and trial. Mean response time (MRT, sum of delay and
      time constant) was calculated with monoexponential fitting. Facial stimulation
      induced acute bradycardia (-10 +/- 5 beats/min in S2 trial). The MRT of HR and Q
      was significantly longer in the S2 trials (46 +/- 35 and 37 +/- 23 s) than in the
      Nr trials (26 +/- 18 and 28 +/- 19 s, respectively), but no significant change in
      VO2 MRT was shown (36 +/- vs. 38 +/- 12 s). These findings suggest that increased
      vagal activity delays the central circulatory responses, which does not alter the
      VO2 kinetics at the onset of stepwise increase in workload. The maintenance of
      VO2 kinetics during acute bradycardia may either reflect the fact that some
      intramuscular processes (such as oxidative enzyme inertia) limit VO2 kinetics or
      alternatively that increased sympathetic vasoconstriction at some remote site
      defends exercising muscle blood flow.

PMID- 9644040
TI  - Lateral parabrachial nucleus modulates baroreflex regulation of sympathetic nerve
      activity.
AB  - Previous studies have demonstrated that the lateral parabrachial nucleus (LPBN)
      is an important site for descending modulation of baroreflex control of heart
      rate. In the present study it was hypothesized that the LPBN neurons may also
      modulate baroreflex control of arterial pressure and sympathetic nerve activity.
      In urethan-anesthetized rats, electrical or chemical activation of the LPBN
      produced a significant reduction in the magnitude of the baroreflex inhibition of
      mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) elicited
      by aortic depressor nerve stimulation. Chemical inactivation of the LPBN resulted
      in a small increase in baroreflex control of MAP, but baroreflex control of RSNA
      was not affected. The results suggest that LPBN neurons have little tonic
      influence over baroreflex control of MAP and RSNA in the anesthetized rat. When
      the LPBN is activated, however, LPBN neurons may function to reduce the capacity
      of the baroreflex to regulate sympathetically mediated increases in arterial
      pressure.

PMID- 9644041
TI  - Contribution of renal nerves to renal blood flow variability during hemorrhage.
AB  - We have examined the role of the renal sympathetic nerves in the renal blood flow
      (RBF) response to hemorrhage in seven conscious rabbits. Hemorrhage was produced
      by blood withdrawal at 1.35 ml.min(-1).kg-1 for 20 min while RBF and renal
      sympathetic nerve activity (RSNA) were simultaneously measured. Hemorrhage was
      associated with a gradual increase in RSNA and decrease in RBF from the 4th min.
      In seven denervated animals, the resting RBF before hemorrhage was significantly
      greater (48 +/- 1 vs. 31 +/- 1 ml/min intact), and the decrease in RBF did not
      occur until arterial pressure also began to fall (8th min); however, the overall
      percentage change in RBF by 20 min of blood withdrawal was similar. Spectral
      analysis was used to identify the nature of oscillations in each variable. Before
      hemorrhage, a rhythm at approximately 0.3 Hz was observed in RSNA, although not
      in RBF, whose spectrogram was composed mostly of lower-frequency (< 0.25 Hz)
      components. The denervated group of rabbits had similar frequency spectrums for
      RBF before hemorrhage. RSNA played a role in dampening the effect of oscillations
      in arterial pressure on RBF as the transfer gain between mean arterial pressure
      (MAP) and RBF for frequencies > 0.25 Hz was significantly less in intact than
      denervated rabbits (0.83 +/- 0.12 vs. 1.19 +/- 0.10 ml.min(-1).mmHg-1).
      Furthermore, the coherence between MAP and RBF was also significantly higher in
      denervated rabbits, suggesting tighter coupling between the two variables in the
      absence of RSNA. Before the onset of significant decreases in arterial pressure
      (up to 10 min), there was an increase in the strength of oscillations centered
      around 0.3 Hz in RSNA. These wer accompanied by increases in the spectral power
      of RBF at the same frequency. Arterial pressure fell in both groups of animals,
      the dominant rhythm to emerge in RBF was centered between 0.15 and 0.20 Hz and
      was present in intact and denervated rabbits. It is speculated that this myogenic
      in origin. We conclude that RSNA can induce oscillations in RBF at 0.3 Hz, plays
      a significant role in altering the effect of oscillations in arterial pressure on
      RBF, and mediates a proportion of renal vasoconstriction during hemorrhage in
      conscious rabbits.

PMID- 9644042
TI  - Acclimation to humid heat lowers resting core temperature.
AB  - The purpose of this study was to test the hypothesis that a reduction in resting
      rectal temperature (Tre) is partially responsible for the attenuation in the rise
      of core temperature during the heat exposure following acclimation to humid heat.
      Nine male volunteers completed 7 days of acclimation, performing 2 h of exercise
      per day in a hot, humid environment (35 degrees C, 75% relative humidity). Mean
      (+/- SD) ending Tre significantly (P < 0.05) decreased from 38.9 +/- 0.5 degrees
      C on day 1 to 38.3 +/- 0.4 degrees C on day 7. Likewise, mean (+/- SD) resting
      Tre significantly (P < 0.05) decreased from 37 +/- 0.3 to 36.7 +/- 0.4 degrees C.
      In fact, all nine men showed a decrease in resting Tre from day 1 to day 7,
      ranging from -0.1 to -0.5 degrees C. In addition, resting Tre and ending Tre were
      significantly correlated (r = 0.68). However, the mean increases in Tre (ending
      Tre minus resting Tre) and heat storage that occurred on each of the 7
      acclimation days were not significantly different. These results support the
      hypothesis that a reduction in resting Tre is partially responsible for the
      attenuation in ending Tre during heat exposure following short-term acclimation
      to humid heat.

PMID- 9644043
TI  - Increased oxidative capacity does not protect skeletal muscle fibers from
      eccentric contraction-induced injury.
AB  - Isometric electrical stimulation was delivered to rabbit dorsiflexor muscles at
      10 Hz for 1 s on and 1 s off over 30 min, 5 days/wk for 3 wk to induce an
      increase in muscle oxidative capacity. Stimulation-trained muscles as well as
      untrained muscles were then subjected to a 30-min eccentric exercise bout to test
      whether increased oxidative capacity provided a protective effect against muscle
      injury. Electrical stimulation results in significant training of both the
      extensor digitorum longus (EDL) and tibialis anterior (TA) muscles, with EDL
      citrate synthase (CS) activity increasing an average of 67% (P < 0.0001) and TA
      CS activity increasing by 27% (P < 0.05). For all parameters measured, the
      magnitude of change was much greater for EDL than for TA muscle. Dorsiflexor
      fatigability decreased significantly during the 3-wk training period (P <
      0.0001), whereas the EDL TA individually showed strong decreasing trends in
      fatigability after training. TA and EDL capillary density measured
      histomorphometrically increased from 839 +/- 56 to 1,026 +/- 71 mm-2 (P = 0.07)
      and from 589 +/- 37 to 792 +/- 66 mm-2 (P < 0.05), respectively. TA and EDL
      capillary-to-fiber ratio increased from 1.32 +/- 0.10 to 1.55 +/- 0.16 (P > 0.2)
      and 1.08 +/- 0.07 to 1.36 +/- 0.14 (P > 0.1), respectively. Type 2A fiber type
      percentage increased after stimulation training by 68% (P < 0.0001) for the EDL
      and by 32% (P > 0.1) for the TA at the expense of type 2D fibers. Despite the
      large training effect for the EDL and the modest training effect for the TA, no
      differences were observed between stimulation-trained and untrained groups for
      maximum dorsiflexion torque (P > 0.3) or maximum tetanic tension (P > 0.3) after
      eccentric contraction-induced injury. Additionally, no significant correlation
      was observed between CS activity and maximum tetanic tension after eccentric
      contraction-induced injury for either muscle (P > 0.2). Thus we conclude that
      increasing muscle oxidative capacity by isometric electrical stimulation training
      did not protect muscle against eccentric contraction-induced injury.

PMID- 9644044
TI  - Persistence of metabolic rhythmicity during fasting and its entrainment by
      restricted feeding schedules in rats.
AB  - The presence of a food-entrainable oscillator (FEO) independent from the SCN is
      now well established, but until now its location and characterization have been
      elusive. Because its expression requires priming of the animal's metabolism
      toward a catabolic state, it is possible that metabolic rhythms may be related to
      FEO. The present study was designed to determine whether metabolic rhythms
      persist during fasting and whether such rhythms could be entrained to a
      restricted feeding schedule. The results indicate persistent rhythms of
      triacylglycerides, free fatty acids, glucose, and proteins during fasting,
      whereas ketone bodies and liver glycogen changed their concentration as a
      function of fasting. Daily food pulses of 2 h entrained the rhythms of
      triacylglycerides and free fatty acids and restored ketone bodies and liver
      glycogen to similar levels as controls. Neither glucose nor proteins were
      affected by the food pulse. These results indicate the relevance of lipid
      metabolism as a phenomenon associated with the FEO.

PMID- 9644045
TI  - Effects of daily sodium intake and ANG II on cortical and medullary renal blood
      flow in conscious rats.
AB  - Implanted optical fibers and laser-Doppler flow measurement techniques were used
      for the sequential measurement of regional renal blood flow in conscious rats to
      determine the effects of an increase of daily NaCl intake on the renal cortical
      blood flow and blood flow to the outer and inner medulla. Cortical blood flow was
      increased significantly (32%) by the second day when NaCl intake was increased
      from 1 to 7 meq/day and was increased further (50%) on the second day after a
      further elevation of NaCl intake to 13 meq/day. Blood flow to the outer and inner
      medulla was not changed as NaCl intake was elevated. The increase in renal
      cortical flow was closely associated with significant reductions in circulating
      concentrations of ANG II from 31 to 16 pg/ml. Rats given a continuous infusion of
      nonpressor does of ANG II (5.0 ng.kg(-1).min-1) to maintain constant plasma
      concentrations of ANG II as sodium intake was increased exhibited no increase of
      cortical flow. We conclude that reductions of plasma ANG II associated with
      incremental increases of daily sodium intake result in a rise of renal cortical
      flow. The elevated blood flow to the renal cortex may enhance sodium excretion
      and contribute to long-term sodium homeostasis.

PMID- 9644046
TI  - Enhanced responses of the chorda tympani nerve to nonsugar sweeteners in the
      diabetic db/db mouse.
AB  - Genetically diabetic db/db mice show greater neural and behavioral responses to
      sugars than lean control mice. The present study examined chorda tympani
      responses of db/db mice to nonsugar sweeteners and their inhibition by a sweet
      response inhibitor, gurmarin. The results showed that responses to sucrose,
      saccharin, glycine, L-alanine, and D-tryptophan, but not to D-phenylalanine, were
      approximately 1.5 times greater in db/db mice than in control mice. Treatment of
      the tongue with gurmarin suppressed responses to these sweeteners in db/db and
      control mice, but the extent of suppression was considerably smaller in db/db
      mice. The magnitudes of gurmarin-sensitive components of the response to
      sweeteners in db/db mice were not significantly different from those in control
      mice, whereas the magnitudes of gurmarin-insensitive components in db/db mice
      were about twice as large as those in control mice. These results suggest that
      the enhancement of chorda tympani responses in db/db mice to sucrose and other
      nonsugar sweeteners may occur through gurmarin-insensitive membrane components.

PMID- 9644047
TI  - Leptin depolarizes rat hypothalamic paraventricular nucleus neurons.
AB  - Leptin, the protein product of the ob/ob gene, is thought to have a central site
      of action, presumably within the hypothalamus, through which it regulates feeding
      behavior. THe paraventricular nucleus (PVN) is one structure that has been
      implicated in regulating feeding behavior. Using patch-clamp recording
      techniques, this study examines the direct membrane effects of leptin on neurons
      in a coronal PVN slice. Bath application of the physiologically active leptin
      fragment (amino acids 22-56) elicited dose-related depolarizations in 82% of the
      type I cells tested (n = 17) and 67% of the type II cells tested (n = 9). By
      contrast, the physiologically inactive leptin fragment (amino acids 57-92) had no
      discernible effect on membrane potential (n = 7). The effects of this peptide
      were unaffected following synaptic isolation of the cells by bath application of
      the sodium channel blocker tetrodotoxin (n = 5). Voltage clamp recordings in six
      cells demonstrated that leptin increased a nonspecific cation conductance with a
      reversal potential near -30 mV. These findings suggest that neurons in PVN may
      play an important role in the central neuronal circuitry involved in the
      physiological response to leptin.

PMID- 9644048
TI  - Bioartificial Organs: Science and Technology. Conference proceedings. Nashville,
      Tennessee, USA. July 21-26, 1996.

PMID- 9644049
TI  - Cancer: Genetics and the Environment. Proceedings of a conference. New York, New
      York, USA. November 15-16, 1996.

PMID- 9644050
TI  - Suicide Research Workshop: From the Bench to the Clinic. Proceedings. Washington
      DC, USA. November 14-15, 1996.

PMID- 9644051
TI  - Synthesis and dopamine receptor selectivity of the benzyltetrahydroisoquinoline,
      (R)-(+)-nor-roefractine.
AB  - (R)-(+)-nor-Roefractine (1) was synthesized by the Bischler-Napieralski route,
      using asymmetric reduction of the 1, 2-didehydro precursor imine with sodium (S)
      N-CBZ-prolinyloxyborohydride. Compound 1 was able to displace [3H]-raclopride (a
      D2 dopamine receptor-selective ligand) from its specific binding sites in rat
      striatum with selectivity vs [3H]-SCH23390 (D1 dopamine receptor-selective
      ligand).

PMID- 9644052
TI  - Isolation and structural studies on the chemical constituents of skimmialaureola 
AB  - Studies on the chemical constituents of the aerial parts of Skimmia laureola have
      led to the isolation of four new alkaloids, ptelefoliarine (1),
      acetoxyptelefoliarine (2), acetoxyedulinine (3), and orixiarine (4). Their
      structures were established by spectroscopic studies.

PMID- 9644053
TI  - Novel quinone methides from Salacia kraussii with in vitro antimalarial activity.
AB  - Three novel quinone methides, i.e., 28-nor-isoiguesterin-17-carbaldehyde (1), 17
      (methoxycarbonyl)-28-nor-isoiguesterin (2), and 28-hydroxyisoiguesterin (3),
      together with the known celastrol (5), pristimerin (6), and isoiguesterol (7),
      were isolated from the roots of Salacia kraussii (Celastraceae) by bioassay
      guided fractionation. The structures of the compounds were determined by DEPT and
      2D NMR techniques. The isolates showed antimalarial activity 30-50-fold greater
      than their cytotoxicity (in HT-29 cells) in vitro, and they showed an additive
      effect when combined with each other. In vivo, 2 was found to be inactive against
      blood stages of Plasmodium berghei in mice after oral and parenteral
      administration, and the compound was toxic with increasing concentrations.

PMID- 9644054
TI  - Theonellapeptolide IIIe, a new cyclic peptolide from the New Zealand deep water
      sponge, Lamellomorpha strongylata.
AB  - The structure, stereochemistry, and conformation of theonellapeptolide IIIe (1),
      a new 36-membered ring cyclic peptolide from the New Zealand deep-water sponge
      Lamellomorpha strongylata, is described. The sequence of the cytotoxic peptolide
      was determined through a combination of NMR and MS-MS techniques and confirmed by
      X-ray crystal structure analysis, which, with chiral HPLC, established the
      absolute stereochemistry.

PMID- 9644055
TI  - Enhancement of NO production in activated macrophages in vivo by an antimalarial
      crude drug, Dichroa febrifuga.
AB  - The effect of an antimalarial crude drug, Dichroafebrifuga Lour. on nitric oxide
      (NO) production in bacillus Calmette Guerin-induced mouse peritoneal macrophages
      activated by lipopolysaccharide was investigated. The NO production was
      significantly enhanced by an oral administration of a MeOH extract of D.
      febrifuga. Febrifugine (1) was isolated as the main active compound, and the
      activation was dose-dependent in the dosage range of 0.1-1 mg/kg/day.

PMID- 9644056
TI  - Gmelinosides A-L, twelve acylated iridoid glycosides from Gmelina arborea.
AB  - Besides the known iridoids 6-O-alpha-L-rhamnopyranosylcatalpol (1), 6-O-(3"-O
      trans-feruloyl)-alpha-L-rhamnopyranosylcatalpol (14), 6-O-(2"-O-acetyl-3", 4"-O
      di-trans-cinnamoyl)-alpha-L-rhamnopyranosylcatalpol (15) and the known
      phenylpropanoid glycosides verbascoside (acteoside) and martynoside, 12 new
      acylated iridoid glycosides named gmelinosides A-L (2-13) have been isolated from
      the leaves of Gmelina arborea. These compounds were structurally characterized
      using a variety of spectral methods.

PMID- 9644057
TI  - Certain norditerpenoid alkaloids and their cardiovascular action.
AB  - Thirteen new derivatives of norditerpenoid alkaloids, namely, 8-deacetyl-8-p
      aminobenzoyldelphinine (1), 8-deacetyl-8-anthranoyldelphinine (2), 8-deacetyl-8
      (4-hydroxy-3-methoxycinnamoyl)delphinine (3), 16-demethoxy-15,16-didehydro-8-p
      anisoyl-14-benzoyldelpho nine (4), 6-acetylheteratisine N-oxide (6), 3,8
      diacetylfalconerine (7), 8-stearoylfalconerine (8), 8-linolenylfalconerine (9),
      13-acetylpyrodelphinine (11), 13-acetyldelphinine N-oxide (13), N-deacetyl-8,9
      diacetyllappaconitine (14), 8, 9-(methylenedioxy)lappaconine (15), and 16
      epipyroaconitine N-oxide (17), were prepared, and their structures were
      established by analysis of spectroscopic data (1D and 2D NMR, HRFABMS). The
      preliminary in vivo cardiovascular action (hypotensive, bradycardic, and
      ventricular arrhythmias) of these new compounds was tested in male Sprague-Dawley
      rats. The results are reported herein.

PMID- 9644058
TI  - Macrocyclic diterpenoids from Euphorbia semiperfoliata.
AB  - In addition to known compounds, the aerial parts of E. semiperfoliata afforded an
      abietanolide (3), 13 jatrophane polyesters (4-9, 12, 14-19), two 4-deoxyphorbol
      diesters (23, 24), and a pair of epimeric diterpenes (21, 22) with a novel carbon
      skeleton, which was named euphoperfoliane. Structures were determined by
      spectroscopic analysis, and the main conformational features of jatropha-6(17),11
      dienes are discussed in detail. The obtained isolation yield of several
      jatrophanes was unprecedented within the spurges (Euphorbia spp.), making E.
      semiperfoliata a unique source of macrocyclic diterpenoids.

PMID- 9644059
TI  - Complement-inhibiting cucurbitacin glycosides from Picria fel-terrae.
AB  - Four cucurbitacin glycosides were isolated from Picriafel-terrae and identified
      by MS and NMR spectroscopy as picfeltarraenin IA (1), picfeltarraenin IB (2),
      picfeltarraenin IV (4), and a new compound picfeltarraenin VI (3)
      (picfeltarraegenin I 3-O-beta-D-xylopyranoside). All four compounds acted as
      inhibitors on both the classical and alternative pathways of the complement
      system, with compound 3 exhibiting the highest inhibitory activity (IC50 29 +/- 2
      microM and 21 +/- 1 microM, respectively). Compounds 1-4 showed no antiviral,
      antibacterial, or antifungal activities. Picfeltarraenin IA and IB were tested in
      an in vitro human tumor cell line panel, but displayed no cytotoxic activity.

PMID- 9644060
TI  - Vanicosides C-F, new phenylpropanoid glycosides from Polygonum pensylvanicum.
AB  - The isolation of the protein kinase C inhibitors, vanicoside A (1) and vanicoside
      B (2), from Polygonum pensylvanicum prompted continued interest in the active
      principles of this plant. A new, more efficient isolation procedure has been
      developed to facilitate separation of homologues of vanicosides A and B from the
      complex extract. Several new phenylpropanoid glycosides have since been isolated.
      The structures of these principles were determined to be 2'-O
      acetylhydropiperoside (4), 6'-O-p-coumarylhydropiperoside (5), 4'-O
      acetylvanicoside A (6), and 3'-O-acetylvanicoside B (7) using negative ion FABMS,
      1H NMR, and 2D NMR techniques.

PMID- 9644061
TI  - Cytotoxic isoflavans from Eysenhardtia polystachya.
AB  - Two new cytotoxic isoflavans, (3S)-7-hydroxy-2',3',4',5', 8-pentamethoxyisoflavan
      (1) and (3S)-3',7-dihydroxy-2',4',5', 8-tetramethoxyisoflavan (2), were isolated
      from the bark and trunks of Eysenhardtia polystachya (Leguminosae), together with
      the known constituents stigmasterol, isoduartin, cuneatin, 7-hydroxy-2',4', 5'
      trimethoxyisoflavone, and 3,4-dimethoxy-8, 9-(methylenedioxy)pterocarpan. The
      structures of 1 and 2 were elucidated on the basis of spectroscopic methods. The
      antimicrobial, cytotoxic, and insecticidal potential of some of these compounds
      were evaluated. The isoflavans 1, 2, and isoduartin (2', 7-dihydroxy-3',4',8
      trimethoxyisoflavan) displayed moderate cytotoxic activity against KB cell lines.

PMID- 9644062
TI  - Lignans from Chilean propolis.
AB  - Three new (1, 3, 4) and two known lignans (2 and 5) were isolated from Chilean
      propolis. Compound 1 was identified as a trimeric coniferyl alcohol acetate and 3
      as the diastereomer of the dimeric coniferyl alcohol acetate 2. Compound 4 was
      identified as a dihydrobenzofuran lignan aldehyde, which was isolated together
      with the related known acetate 5.

PMID- 9644063
TI  - Cytotoxic quassinoids from Simaba cedron.
AB  - Four new quassinoids, cedronolactones A-D (1-4), together with nine known
      compounds, simalikalactone D (5), chaparrinone (6), chaparrin (7), glaucarubolone
      (8), glaucarubol (9), samaderine Z (10), guanepolide (11), ailanquassin A (12),
      and polyandrol (13), were isolated from the wood of Simaba cedron. The chemical
      structures of 1-4 were elucidated on the basis of their chemical and spectral
      properties. Cedronolactone A (1) was shown to exhibit a significant in vitro
      cytotoxicity (IC50 0.0074 microg/mL) against P-388 cells.

PMID- 9644064
TI  - Cytotoxic and insecticidal constituents of the unripe fruit of Persea americana.
AB  - Unripe avocado fruit (Persea americana) was subjected to a bioactivity-directed
      fractionation, as monitored via the brine shrimp lethality assay, to isolate
      three major bioactive constituents (1-3). Compounds 1-3 all have a 1,2,4-triol
      moiety and a long aliphatic chain that terminates as either an alkane, alkene, or
      alkyne, respectively; 1 is new, while 2 and 3 have been described previously but
      not as cytotoxic or pesticidal agents. All have activity against six human tumor
      cell lines in culture and show selectivity for human prostate adenocarcinoma (PC
      3) cells with 3 being nearly as potent as adriamycin. Also, when tested against
      yellow fever mosquito larva, 3 was more effective than rotenone, a natural
      botanical insecticide and positive control.

PMID- 9644065
TI  - Hovetrichosides C-G, five new glycosides of two auronols, two neolignans, and a
      phenylpropanoid from the bark of Hovenia trichocarea.
AB  - Two 2-hydroxy-2-benzylcoumaranone glycosides, 2,4, 6-trihydroxy-2-[(4'
      hydroxyphenyl) methyl]-3(2H)-benzofuranone-4-yl-beta-D-glucopyranoside (maesopsin
      4-O-glucoside) (1) and 2,4,6-trihydroxy-2-[(4'-hydroxyphenyl) methyl]-3(2H)
      benzofuranone-4-yl-beta-D-glucopyranosido-4'-y l-alpha-L -rhamnopyranoside
      (maesopsin 4-O-glucosido 4'-O-rhamnoside) (2), two neolignan glycosides, 2R-(E)
      2, 3-dihydro-2-(4'-hydroxy-3'-methoxylphenyl)-5-(3"-hydroxy-1"-pro pen yl) -7
      methoxy-3-benzofuranmethanol-4'-yl-beta-D-glucopyranosyl-(1-->3 )-[ beta-D
      glucopyranosyl-(l-->2)]-beta-d-glucopyranoside (3) and (threo) 1-(4'-hydroxy-3'
      methoxy)-2-(4"-hydroxymethyl-2", 6"-dimethoxyphenoxy)-propane-1,3-diol-4'-yl-beta
      d-glucopynosid e (4), and a phenylpropanoid glycoside, 3-methoxy-5-(2'-propenyl)
      1, 2-benzenediol-1-yl-beta-D-apiofuranosyl-(1-->6)-beta-D- glucopyransodie (5)
      were isolated from the bark of Hovenia trichocarea. Compounds 1-5 were named
      hovetricosides C-G, respectively, and their structures were established by
      extensive NMR experiments and chemical methods. Also obtained in this
      investigation were the known compounds acanthoside B, kelampayoside A,
      shashenoside I, and 3,4, 5-trimethoxyphenol-1-O-beta-D-xylopyranosyl-(1-->6)-beta
      D- glucopyranoside.

PMID- 9644066
TI  - Epolones: novel sesquiterpene-tropolones from fungus OS-F69284 that induce
      erythropoietin in human cells.
AB  - In the course of our screening for small molecule modulators of erythropoietin
      gene expression, two novel sesquiterpene tropolones and pycnidone were isolated
      from a culture of OS-F69284 (ATCC 74390). Their structures were elucidated by
      extensive 1H and 13C NMR spectroscopic studies and chemical reactions. These
      compounds induced erythropoietin gene expression 5-fold at a concentration of 1
      1.6 microM.

PMID- 9644067
TI  - 5-Methoxyjusticidin A, a new arylnaphthalene lignan from Protium unifoliolatum.
AB  - A new arylnaphthalene lignan, 9-(1,3-benzodioxol-5-yl)-4,5,6, 7
      tetramethoxynaphtho[2,3-C]furan-1(3H)-one (5-methoxyjusticidin A, 1), was
      isolated from a Et2O extract of the wood of Protium unifoliolatum. The structure
      of 1 was determined by both spectroscopic and X-ray crystallographic methods.

PMID- 9644068
TI  - New sesquiterpenoids from the jordanian medicinal plant inula viscosa 
AB  - Four new and 14 known compounds have been isolated from Inula viscosa of
      Jordanian origin. The new isolates are 11(13)-eudesmen-12-oic acids, 3beta
      hydroxyilicic acid (1), 3alpha-hydroxy-epi-ilicic acid (2), 2alpha-hydroxyilicic
      acid (3) and 9beta-hydroxy-2-oxoisocostic acid (4).

PMID- 9644069
TI  - A new benzoylglucoside and a new prenylated isoflavone from lophira lanceolata 
AB  - A new benzoylglucoside, lanceoloside A (1), and a new prenylated isoflavone,
      lanceolone (2), have been isolated from the air-dried leaves of Lophira
      lanceolata. Both structures were established from spectroscopic and chemical
      evidence.

PMID- 9644070
TI  - Mollenines A and B: new dioxomorpholines from the ascostromata of Eupenicillium
      molle.
AB  - Two new dioxomorpholines (1 and 2) have been isolated from the sclerotioid
      ascostromata of Eupenicillium molle (NRRL 13062). Their structures were
      determined by analysis of NMR data. Mollenine A (1) exhibited moderate
      cytotoxicity and antibacterial activity, but neither compound displayed
      significant antiinsectan activity.

PMID- 9644071
TI  - Magnone A and B, novel anti-PAF tetrahydrofuran lignans from the flower buds of
      Magnolia fargesii.
AB  - In a search for platelet-activating-factor (PAF) antagonists, two new lignan
      compounds were isolated from the Chinese crude drug shin-i, the flower buds of
      Magnolia fargesii. Their structures were elucidated as (2S,3R,4R)-tetrahydro-2
      (3,4-dimethoxyphenyl)-4-(3, 4-dimethoxybenzoyl)-3-(hydroxymethyl)furan (magnone
      A, 1) and (2S,3R, 4R)-tetrahydro-2-(3,4,5-trimethoxyphenyl)-4-(3, 4
      dimethoxybenzoyl)-3-(hydroxymethyl)furan (magnone B, 2). Magnones A and B showed
      antagonistic activity against PAF in the [3H]PAF receptor binding assay with the
      IC50 values of 3.8 x 10(-5) M and 2.7 x 10(-5) M, respectively.

PMID- 9644072
TI  - Two new ergostane-type steroidal lactones from Withania coagulans.
AB  - Two new withanolides (steroidal lactones) named coagulin F [27-hydroxy-14,20
      epoxy-1-oxo-(22R)-witha-3,5,24-trienolide] (1) and coagulin G [17beta,27
      dihydroxy-14,20-epoxy-1-oxo-(22R)-witha-2,5, 24-trienolide] (2) were isolated
      from the whole plant of Withania coagulans, and their structures were deduced by
      spectral analysis.

PMID- 9644073
TI  - Two 6-substituted 5,6-dihydropyran-2-ones from piper reticulatum 
AB  - The Me2CO extract of the aerial parts of Piper reticulatum yielded two 6
      substituted 5,6-dihydropyran-2-ones 1 and 2 and dihydrowisanidine. The structures
      of 1 and 2 were elucidated by spectroscopic methods.

PMID- 9644074
TI  - Binaphthalenone glycosides from African chewing sticks, Diospyros lycioides.
AB  - Our laboratory has engaged in the exploration of active antimicrobial principles
      present in chewing sticks commonly used by the African and Middle Eastern
      countries as a mechanical oral hygiene aid in place of tooth brushing. During
      this investigation, a methanol extract from the twigs of Diospyros lycioides, a
      Namibia tooth cleaning stick, demonstrated antimicrobial activity against common
      oral pathogens including Streptococcus mutans and Porphyromonas gingivalis (MICs
      2.5 and 0.156 mg/mL). Subsequent fractionation and purification of this extract
      led to the identification of two novel binaphathalenone glycosides: 1', 2
      binaphthalen-4-one-2',3-dimethyl-1,8'-epoxy-1,4',5,5',8, 8'-hexahydroxy-8-O-beta
      glucopyranosyl-5'-O-beta-xylopyranosyl(1-- >6) -beta-glucopyranoside (1) and 1',2
      binaphthalen-4-one-2', 3-dimethyl-1,8'-epoxy-1,4',5,5',8,8'-hexahydroxy-5', 8-di
      O-beta-xylopyranosyl(1-->6)-beta-glucopyranoside (2). Their structures were
      established using spectroscopic techniques. Examination of the antimicrobial
      activity of these two compounds revealed positive but only marginal growth
      inhibition against the test cariogenic pathogens, S. sanguis and Streptococcus
      mutans.

PMID- 9644075
TI  - Synthesis of 4-acetylbenzoxazolin-2(3H)-one reported from zea mays 
AB  - A three-step alternative synthesis of 4-acetylbenzoxazolin-2(3H)-one (4) is
      reported. Starting from inexpensive 3-hydroxyacetophenone (1) 3-hydroxy-2
      nitroacetophenone (2) is prepared by nitration followed by catalytic
      hydrogenation to yield 2-amino-3-hydroxyacetophenone (3) in which a C=O unit is
      inserted by means of bis(trichloromethyl)carbonate (triphosgene) in the presence
      of triethylamine to afford 4 in 35% overall yield.

PMID- 9644076
TI  - New ceramide from marine sponge Haliclona koremella and related compounds as
      antifouling substances against macroalgae.
AB  - A new ceramide N-docosanoyl-d-erythro-(2S, 3R)-16-methyl-heptadecasphing-4(E)
      enine (C22 ceramide) was isolated from the marine sponge Haliclona koremella as
      an antifouling substance against macroalgae. The structure of this substance was
      elucidated by spectral means. Antifouling activity of several related compounds
      was also examined.

PMID- 9644077
TI  - Sesquiterpenes from the leaves of Tithonia diversifolia.
AB  - Two new compounds, a germacrane sesquiterpene, 1-acetyltagitinin A (1), and a
      guaianane sesquiterpene, 8beta-isobutyryloxycumambranolide (2), were isolated
      from leaves of Tithonia diversifolia, together with two known compounds, methyl
      3alpha-acetoxy-4alpha-hydroxy-11(13)-eudesmen-12-oa te and tagitinin A. The
      structures of compounds 1 and 2 were elucidated on the basis of spectral and
      chemical evidence.

PMID- 9644078
TI  - New diterpenes from the heartwood of Chamaecyparis obtusa var. formosana.
AB  - An abietane diterpene, 11,14-dihydroxy-8,11,13-abietatrien-7-one (1); a seco
      abietane diterpene, obtuanhydride (2); and an isopimarane diterpene, 18,19-O
      isopropylidene-18, 19-dihydroxyisopimara-8(14),15-diene (3) were isolated from
      the heartwood of Chamaecyparis obtusa var. formosana. The structures of these new
      compounds were elucidated by spectroscopic methods.

PMID- 9644079
TI  - Studies on the secondary metabolites from the Indian gorgonian Subergorgia
      suberosa: isolation and characterization of four analogues of the cardiotoxin
      subergorgic acid.
AB  - Chemical investigation of the methanol extract of the Indian ocean gorgonian
      coral Subergorgia suberosa resulted in isolation and identification of four novel
      compounds 2-5. Structural investigation revealed compound 1 to be subergorgic
      acid and the others its analogues.

PMID- 9644080
TI  - Isolation of a novel diterpene triacetate from two soft corals of the order
      alcyonacea 
AB  - Alcyonolide 5 (5), a novel diterpene triacetate, has been isolated from two soft
      corals of the order Alcyonacea.

PMID- 9644081
TI  - A new taxane diterpenoid from Taxus mairei.
AB  - A new 11(15-->1)-abeotaxane diterpene, taxumairol K (1), has been isolated from
      the ethanolic extract of the roots of Formosan Taxus mairei (Lemee & Levl.) S. Y.
      Hu. The structure of 1 was determined as 9alpha-(benzoyloxy)-2alpha,4alpha-
      diacetoxy-5beta ,20-epoxy-1beta, 7beta,10beta,13alpha-tetrahydroxy-11(15-->1)
      abeota xane on the basis of spectral analysis. Taxumairol K (1) exhibited mild
      cytotoxicity against HeLa tumor cells.

PMID- 9644082
TI  - Biosynthesis of phytol in the cyanobacterium synechocystis sp. UTEX 2470:
      utilization of the non-mevalonate pathway 
AB  - The biosynthesis of phytol in the cyanobacterium Synechocystis sp. UTEX 2470 has
      been examined using 6,6-2H2-d-glucose, 2-13C-d-glucose, and U-13C6-d-glucose as
      precursors. Analysis of the isolated phytol using deuterium or 13C NMR showed
      labeling patterns consistent with incorporation of labeled glucose via the non
      mevalonate pathway to terpenes.

PMID- 9644083
TI  - Novel cytotoxic cembranoids from the soft coral Sinularia flexibilis.
AB  - Three new cytotoxic cembranoid diterpenes, sinuflexolide (1),
      dihydrosinuflexolide (2), and sinuflexibilin (3), have been isolated from the
      soft coral Sinularia flexibilis. The structures of compounds 1-3 were determined
      by spectral and X-ray crystallographic analysis.

PMID- 9644084
TI  - New pyrrole alkaloids from Solanum sodomaeum.
AB  - Two new pyrrole alkaloids, solsodomine A and B, were isolated from the fresh
      berries of Solanum sodomaeum L., collected from the Libyan desert. The structures
      of these compounds were established by 2D-NMR, including 15N NMR spectroscopy and
      chemical degradation. Solsodomine A (1) shows activity against Mycobacterium
      intracellulare. This is the first report of pyrrole alkaloids from the genus
      Solanum.

PMID- 9644085
TI  - Two (Z)-dehydrobutyrine-containing microcystins from a hepatotoxic bloom of
      Oscillatoria agardhii from Soulseat Loch, Scotland.
AB  - Two (Z)-dehydrobutyrine(Dhb)-containing microcystins, [d-Asp3, (Z)
      Dhb7]microcystin-HtyR (1) and [d-Asp3, (Z)-Dhb7]microcystin-LR (2), were isolated
      from a hepatotoxic bloom of the cyanobacterium Oscillatoria agardhii from a
      freshwater lake in Scotland. The geometrical structure of the Dhb units in the
      microcystins was determined as Z on the basis of NOE and ROESY experiments.

PMID- 9644086
TI  - Dehydroradiosumin, a trypsin inhibitor from the cyanobacterium Anabaena
      cylindrica.
AB  - Dehydroradiosumin, a novel potent trypsin inhibitory dipeptide, was isolated from
      the freshwater cyanobacterium Anabaena cylindrica (NIES-19). Its structure was
      elucidated as 1 on the basis of 2D NMR data and chemical degradation. The IC50 of
      1 against trypsin was 0.1 microg/mL.

PMID- 9644087
TI  - Isolation of 2-(3'-bromo-4'-hydroxyphenol)ethanamine from the New Zealand
      ascidian Cnemidocarpa bicornuta.
AB  - From the ascidian Cnemidocarpa bicornuta, 2-(3'-bromo-4'-hydroxyphenol)ethanamine
      (3'-bromotyramine) (1) has been isolated along with the previously reported
      sponge metabolite, 1,3-dimethylisoguanine. The structure of 1 was confirmed by
      synthesis.

PMID- 9644088
TI  - Dihydrotubastrines: phenethylguanidine analogues from the Indo-Pacific marine
      sponge Petrosia cf. contignata.
AB  - Two phenethylguanidine derivatives, 7,8-dihydrotubastrine (1) and 4-deoxy-7,8
      dihydrotubastrine (2), along with the sterol xestobergsterol A (3), were isolated
      from the marine sponge Petrosia cf. contignata. The structures of the new natural
      products 1 and 2 were based on spectroscopic data and comparison to the
      literature properties for semisynthetic 1. This is the first example from this
      compound class with a saturated acyclic C2 unit.

PMID- 9644091
TI  - From the Editors.

PMID- 9644092
TI  - Zinc, iron, and magnesium status in athletes--influence on the regulation of
      exercise-induced stress and immune function.
AB  - Intense physical exercise has been shown to be associated with immunosuppression
      and increased rate of infection. The immunosuppressive effect of exhaustive
      exercise has been attributed to a reduced helper/suppressor T-cell ratio, low
      salivary levels of immunoglobulin-A, decreased lymphocyte proliferative response
      and natural killer cell activity, and elevation of stress hormones. Yet some
      athletes can withstand intense training periods without health problems while
      others are prone to infections. Thus it has been postulated that other factors
      may interfere with immunoregulation. The notion that macro- and micronutrients
      are involved in the regulation of immunological processes and the ability to cope
      with muscular and systemic exercise stress has been gaining attention.
      Particularly trace elements have been shown to be related to cell mediated and
      humoral immunity such as NK-cell activity, T- and B-cell functions, and cytokine
      release. Many investigations have reported decreased concentrations of trace
      elements in blood and tissues after training and competition. However, the
      magnitude of losses is highly dependent on the type and intensity of exercise,
      the individual regulatory state, and most important, nutrition. This paper
      reviews the data on zinc, iron, and magnesium status in athletes and summarizes
      the consequences of deficiencies in these trace elements regarding exercise
      tolerance and immune function. These elements were chosen since there is evidence
      they are related to exercise-induced stress and immune function.

PMID- 9644093
TI  - Immunological hazards from nutritional imbalance in athletes.
AB  - This review examines the influences of nutritional imbalance on immune function
      of competitive athletes, who may adopt an unusual diet in an attempt to enhance
      performance. A major increase in body fat can have adverse effects on immune
      response. In contrast, a negative energy balance and reduction of body mass are
      likely to impair immune function in an already thin athlete. A moderate increase
      in polyunsaturated fat enhances immune function, but excessive consumption can be
      detrimental. Since endurance exercise leads to protein catabolism, an athlete may
      need 2.0 g/kg protein rather than the 0.7-1.0 g/kg recommended for a sedentary
      individual. Both sustained exercise and overtraining reduce plasma glutamine
      levels, which may contribute to suppressed immune function postexercise. A large
      intake of carbohydrate counters glutamine depletion but may also modify immune
      responses by altering the secretion of glucose-regulating hormones. Vitamins are
      important to immune function because of their antioxidant role. However, the
      clinical benefits of vitamin C supplementation are not enhanced by the use of
      more complex vitamin mixtures, and excessive vitamin E can have negative effects.
      Iron, selenium, zinc, calcium, and magnesium ion all influence immune function.
      Supplements may be required after heavy sweating, but an excessive intake of iron
      facilitates bacterial growth. In making dietary recommendations to athletes, it
      is important to recognize that immune response can be jeopardized not only by
      deficiencies but also by excessive intake of certain nutrients. The goal should
      be a well-balanced diet.

PMID- 9644094
TI  - Glutamine, exercise, and the immune system--is there a link?
AB  - Glutamine is known to be important for cells replicating in culture. It has been
      proposed that the decrease in plasma glutamine concentration in relation to
      catabolic conditions, including strenuous exercise, resulting in a lack of
      glutamine for cells of the immune system, is responsible for the transient
      postexercise immunosuppression. This review discusses the potential role of
      glutamine on the postexercise in-vitro changes in immune parameters. Furthermore,
      the value of glutamine as a nutritional supplement to athletes and the possible
      influence on these parameters is reviewed.

PMID- 9644095
TI  - Influence of carbohydrate on the immune response to intensive, prolonged
      exercise.
AB  - Many components of the immune system exhibit change after prolonged, heavy
      exertion, indicating that the immune system is suppressed and stressed, albeit
      transiently, following prolonged endurance exercise. Whether these immune changes
      compromise host protection against viruses is still undetermined. Various
      attempts have been made to alter the changes in immunity following heavy exertion
      through nutritional or chemical means, with the most impressive results reported
      thus far in the carbohydrate supplementation studies. Earlier research had
      established that a reduction in blood glucose levels is linked to hypothalamic
      pituitary-adrenal activation, an increased release of adrenocorticotrophic
      hormone and cortisol, increased plasma growth hormone, decreased insulin, and a
      variable effect on blood epinephrine levels. Data from two studies of 30 marathon
      runners and 10 triathletes suggest that carbohydrate compared to placebo
      ingestion is associated with higher plasma glucose levels, an attenuated cortisol
      and growth hormone response, fewer perturbations in blood immune cell counts,
      lower granulocyte and monocyte phagocytosis and oxidative burst activity, and a
      diminished pro- and anti-inflammatory cytokine response. Overall, the hormonal
      and immune responses to carbohydrate compared to placebo ingestion suggest that
      physiologic stress is diminished, although clinical significance awaits further
      research.

PMID- 9644096
TI  - Importance of TNF-alpha and leptin in obesity and insulin resistance: a
      hypothesis on the impact of physical exercise.
AB  - Obesity is associated with an increased incidence of insulin resistance,
      dyslipoproteinemia, and hypercoagulability. In a more recently established
      hypothesis of body weight control and regulation of metabolism, the adipocyte
      secretes leptin and locally expresses TNF-alpha, the latter being responsible for
      the expression of metabolic cardiovascular risk factors. TNF-a mRNA expression
      and TNF-alpha protein are greatly increased in adipose tissue from obese animals
      and humans. Elevated TNF-alpha expression induces insulin resistance by
      downregulating the tyrosine kinase activity of the insulin receptor and
      decreasing the expression of GLUT-4 glucose transporters. TNF-alpha also reduces
      lipoprotein lipase activity in white adipocytes, stimulates hepatic lipolysis,
      and increases plasminogen activator inhibitor-1 content in adipocytes. Moreover,
      adipocytes secrete leptin, a molecule with a secondary cytokine structure whose
      concentrations correlate with the amount of fat tissue. Increased leptin levels
      downregulate appetite and increase sympathetic activity and thermogenesis in the
      hypothalamus. Diet-induced weight loss reduces adipose TNF-alpha expression and
      serum leptin levels and is associated with improved insulin sensitivity and lipid
      metabolism. Although exercise has also been shown to reduce leptin levels, an
      influence on TNF-a expression in adipocytes or muscle cells has not yet been
      demonstrated.

PMID- 9644111
TI  - Diacylglycerol molecular species in plasma membrane and microsomes change
      transiently with endothelin-1 treatment of glioma cells.
AB  - Agonist-induced intracellular signal transduction often involves activation of
      protein kinase C by diacylglycerol (DAG) released from membrane phospholipids by
      phospholipases. Using either DAG kinase or HPLC assays to quantitatively
      determine DAG mass, we observed a time-dependent increase in DAG accumulation
      upon incubation of rat C6 glioma cells with 200 nM endothelin-1 (ET-1). Total
      cell DAG rapidly increased by 25-35% from a basal level of 4.5 +/- 0.3 nmol/mg
      protein during one min of ET-1 treatment and remained constant or slightly
      decreased between 1 and 2 min. Thereafter, DAG increased to a maximum (1.6-fold
      above basal) by 5-10 min. and remained elevated to 30 min. Resolution of DAG
      molecular species by HPLC after incubation of cells with ET-1 revealed that
      accumulation of DAG species differed in total cell lysate and subcellular
      compartments. In plasma membrane, major DAG species increased at 1 min. followed
      by a decrease at 10 min. whereas in microsomes DAG species did not change at 1
      min. and decreased at 10 min. Although phospholipid sources of DAG species were
      not identified specifically, there was preferential hydrolysis of molecular
      species of phospholipid for DAG production. We propose that molecular species of
      DAG produced at the plasma membrane may be transferred to the endoplasmic
      reticulum so that phospholipid resynthesis can replenish molecular species
      initially utilized in signal transduction.

PMID- 9644112
TI  - Effects of systemic prostaglandin E1 on splanchnic and peripheral haemodynamics
      in control subjects and in patients with cirrhosis.
AB  - Prostaglandins of the E series showed metabolic and clinical effects in patients
      with liver disease; changes in splanchnic haemodynamics might be involved. Blood
      flow in femoral and mesenteric artery and in the portal vein was measured by echo
      Doppler in 10 controls and 14 cirrhotic patients, in response to the systemic
      infusion of a PGE1 analogue (30 micrograms/h for 2-6 h) or saline, performed in
      random order. Intraparenchymal resistive and pulsatility indices in the liver,
      spleen and kidney were also measured. In both groups PGE1 increased femoral
      artery flow by 40%, irrespective of infusion time. Heart rate increased slightly,
      whereas mean arterial pressure decreased. There were no changes in mesenteric
      artery and portal vein flow, as well as in resistance indices. Saline infusion
      increased femoral artery flow by 4%. PGE1 infusion does not produces significant
      effects on Doppler-assessed splanchnic hemodynamics in controls and in cirrhotic
      patients, in spite of significant effects on peripheral circulation.

PMID- 9644114
TI  - Effects of Lorenzo's Oil on peroxisomes in healthy mice.
AB  - We investigated peroxisomal alterations in mice treated with different doses of
      Lorenzo's Oil (a therapy for X-linked adrenoleukodystrophy patients) for up to
      100 days. Hepatic erucic acid levels were already significantly increased 2.2
      fold and 2.6-fold in mice treated with 10% and 20% Lorenzo's Oil for 21 days,
      respectively. No lipidosis was found in liver, myocardium and kidney of any of
      the treated mice. While hepatic catalase, lauroyl-CoA oxidase and glycolate
      oxidase, and renal catalase activities were not induced by either diet,
      myocardial catalase activity was increased in most groups. This suggests that the
      mechanism of the effect of Lorenzo's Oil in X-linked adrenoleukodystrophy
      patients may not be a direct effect on the peroxisomes.

PMID- 9644113
TI  - Effects of oxysterols upon macrophage and lymphocyte functions in vitro.
AB  - Oxygenated derivatives of cholesterol (oxysterols), found in high concentrations
      in atherosclerotic lesions, are potent immunosuppressive agents inhibiting T-cell
      responses to different stimuli. The action of oxysterols on macrophage functions
      and macrophage-lymphocyte interaction has been poorly investigated. In this work,
      the effects of 25-hydroxycholesterol (25-OHCh) and 7-ketocholesterol (7-KCh) upon
      some functions of murine peritoneal macrophage (PM), such as generation of
      reactive oxygen intermediates (ROI), secretion of neopterin and interleukin-1 (IL
      1)-like activity, Fc-receptor (FcR) activity, and murine and human lymphocyte
      functions, participating in lymphocyte-macrophage interactions, such as
      macrophage-activating factor (MAF) and Ia-inducing factor (IaIF) secretion, were
      studied in vitro. 7-KCh in concentration of 5 micrograms/mL culture medium only,
      but not 25-OHCh, significantly inhibited ROI generation by zymosan-stimulated PM.
      Pretreatment of PM for 22 h with 25-OHCh and 7-KCh led to the decrease of IL-1
      like activity secretion. 25-OHCh and 7-KCh inhibited both FcR-dependent binding
      and phagocytosis of sheep red blood cells (SRBC). Oxysterols did not change both
      spontaneous and lipopolysaccharide-stimulated secretion of neopterin by PM. 25
      OHCh dose-dependently and more efficiently than 7-KCh inhibited murine splenocyte
      secretion of MAF, which activity was determined by the ability of splenocyte
      conditioned medium to stimulate ROI generation in PM. Both 25-OHCh and 7-KCh
      inhibited significantly proliferative activity of human mixed lymphocyte culture
      (MLC), as well as lymphocyte secretion of IaIF, which stimulates the expression
      of HLA antigens in cultured human monocytes. Purified Ch did not alter these
      parameters. These data showed, that some inflammatory functions of macrophages
      and lymphocytes may be modified by such environmental conditions as the presence
      of oxysterols.

PMID- 9644115
TI  - Polyphosphoinositide synthesis in human neutrophils. Effects of a low metabolic
      energy state.
AB  - Phosphatidylinositol (PtdIns) synthesis and polyphosphoinositide (PPI) formation
      were measured as the incorporation of [32P]orthophosphate ([32P]Pi) or
      [3H]inositol into non-stimulated intact human neutrophil membrane phospholipids.
      The rate of PtdIns "de novo" synthesis appeared to be a slow mechanism when
      compared to the rapid incorporation of [32P]Pi into PPIs. Of the "de novo"
      synthesized [3H]PtdIns, 70% was further phosphorylated to PPI. Nevertheless, this
      PPI pool represented less than 0.01% of the total nmols of PPIs formed evaluated
      as [32P]Pi labeling, indicating that PPI formation mainly involves a no "de novo"
      synthesized phosphatidylinositol pool. When evaluated at short incubation times,
      oscillations in the formation of PPIs were detected. A rapid phase was
      characterized after 30 s of incubation with [32P]Pi Phosphorylation levels
      returned to an equilibrium state within a minute, and the second phase peaked at
      5 min., returning to equilibrium at 15 min. The fluctuant kinetics though not the
      equilibrium level of PPI formation, could be abolished by neomycin. On the other
      hand, a selective inhibition of the rapid phase of PPI synthesis occurred in the
      presence of the tyrosine kinase inhibitor genistein. When the incorporations of
      [gamma-32P]-adenosine triphosphate (ATP) or [32P]Pi into human neutrophil
      particulate fraction membranes were evaluated, PPIs synthesis showed fluctuations
      independently of the precursor used. Noticeably, [32P]from [32P]Pi was
      incorporated more efficiently into PPIs than that from [gamma-32P]ATP, when
      evaluated in parallel using equal specific activities for both radiolabeled
      precursors and under non-ATP synthesizing conditions. Moreover, the incorporation
      of [32P]Pi into particulate fraction PPIs was not abolished by high
      concentrations of non-radiolabeled ATP, and metabolically inhibited PMNs showed
      high rates of PPI synthesis. These data suggest that PPI formation is not
      necessarily a futile cycle in PMNs.

PMID- 9644116
TI  - Multiresistance and 'superbugs'.

PMID- 9644117
TI  - Keeping the customer satisfied.

PMID- 9644118
TI  - The United Kingdom's hepatitis B immunisation strategy--where now?
AB  - The World Health Organization recommended in 1992 that all countries should
      introduce universal hepatitis B vaccination into their immunisation schedules by
      December 1997. Over 80 countries, many of them in western Europe, have complied
      with the recommendation, but, in the United Kingdom (UK), hepatitis B vaccine is
      offered to selected high risk population groups only. Vaccination uptake in many
      of these groups is poor and transmission of hepatitis B remains a problem. The
      current incidence of hepatitis B is lower in the UK than in countries that have
      adopted a universal approach. It is impossible, however, to predict the number of
      acute infections that might occur in an unvaccinated teenage population in the
      year 2015 if the UK's current strategy remains unaltered. Universal immunisation
      would guarantee that hundreds, if not thousands, of acute illnesses and an
      appreciable number of severe outcomes would be prevented each year. The authors
      believe that funding this intervention would be money well spent.

PMID- 9644119
TI  - Complications of bacille Calmette-Guerin (BCG) vaccination and immunotherapy and
      their management.
AB  - Complications of bacille Calmette-Guerin (BCG) vaccination are uncommon. Fewer
      than one in 1000 people vaccinated develop significant local reactions, and
      serious disseminated disease develops in fewer than one in a million. Localised
      complications--which include hypersensitivity reactions, abscesses at the
      injection site, and localised lymphadenopathy--are usually self limiting. They
      usually result from faulty technique, including the accidental intracutaneous
      injection of the stronger percutaneous vaccine, or poor selection of subjects for
      vaccination. Abscesses at the injection site usually respond to drainage and
      chemotherapy with isoniazid or erythromycin. Lymphadenopathy responds poorly to
      antimicrobial treatment and surgery may be needed for suppurating or discharging
      lesions to hasten recovery and give a good cosmetic result. Disseminated disease
      usually occurs in people with impaired immunity, in whom it is often fatal. BCG
      should never be given to people who are known to be infected with HIV, but the
      risk of complications in children born to HIV infected mothers is low.
      Disseminated disease can also result from intravesical instillation of BCG to
      treat bladder cancer, but this responds to antituberculosis chemotherapy.

PMID- 9644120
TI  - Laboratory surveillance of hepatitis C virus infection in England and Wales: 1992
      to 1996.
AB  - Screening assay for antibody to hepatitis C virus (HCV) became available late in
      1990 and their use has subsequently become widespread. Laboratories in England
      and Wales reported 5232 confirmed HCV infections to the PHLS Communicable Disease
      Surveillance Centre (CDSC) between 1992 and 1996. Fifty-seven per cent (2976) of
      reports included risk factor information, 80% of which (2382) identified
      injecting drug use as the main route of transmission. Thirty-one per cent of
      reports (1640) included clinical information: 41% (665) were asymptomatic, 57%
      (938) had symptoms, signs, or biochemical abnormalities of hepatic origin, and
      2.2% (37) had non-hepatic conditions. To enhance these data two additional
      surveys have been undertaken to collect data on all anti-HCV tests performed in
      public health laboratories. In 1993, a retrospective survey of people tested
      between 1990 and 1993 revealed that the prevalence of antibody was highest
      (222/331 [67%]) among injecting drug users and recipients of blood or blood
      products (189/548 [34%]) and lower among other groups. In a prospective survey of
      HCV tests performed in transfusion recipients in early 1995, the prevalence of
      antibody was higher in those transfused before 1985 (11/418 [2.6%]) than in those
      transfused after 1985 (14/1441 [1.0%]). Reports of confirmed infections are a
      useful method of monitoring hepatitis C infection but additional data on testing
      are needed to interpret trends overall and in specific risk groups.

PMID- 9644121
TI  - Hepatitis C virus antibody prevalence among injecting drug users in Glasgow has
      fallen but remains high.
AB  - Few data have been published on the prevalence of hepatitis C virus (HCV) among
      injecting drug users (IDUs) in the United Kingdom. This study compares the
      prevalence of antibody against HCV (anti-HCV) among IDUs in Glasgow in 1990 (when
      Glasgow's needle/syringe exchange programme had become established) with that in
      1995. Serum left over from specimens taken for named HIV antibody testing was
      tested anonymously for anti-HCV. The prevalence of anti-HCV fell significantly
      between 1990 and 1995 among IDUs of all ages (90% to 77%), IDUs aged 15 to 19
      years (92% to 29%), and IDUs aged 20 to 24 years (91% to 65%). This study
      suggests that the incidence of HCV infection among young IDUs fell in the early
      to mid 1990s, after the establishment of Glasgow's needle/syringe exchange scheme
      between 1988 and 1990. Since almost a third of injectors under 20 years of age
      when tested in 1995 had been infected with HCV, however, other interventions may
      be needed to prevent the spread of HCV in this high risk group.

PMID- 9644122
TI  - Occupationally acquired infectious disease in the United Kingdom: 1996 to 1997.
AB  - The incidence of occupationally acquired infectious diseases, has, up to now,
      been unknown. A reporting scheme for consultants in communicable disease control
      (CCDCs) (and their equivalents) throughout the United Kingdom was set up in
      October 1996 to estimate its extent. Monthly reporting cards were sent to CCDCs
      asking for brief details of all new cases of occupationally acquired infectious
      disease seen by them. Between October 1996 and September 1997, 1037 new cases
      were notified by CCDCs. The highest rates were among employees in food production
      and catering, farming, and among care workers, particularly in residential homes.
      During the same period an estimated 257 cases were reported in comparable
      surveillance schemes by chest physicians, occupational physicians and
      dermatologists. These figures probably underestimate the number of infections
      acquired in association with work substantially, and highlight diarrhoeal disease
      as the commonest problem.

PMID- 9644123
TI  - Occupational acquisition of HIV infection among health care workers in the United
      Kingdom: data to June 1997. Local Collaborators, PHLS AIDS and STD Centre,
      Scottish Centre for Infection and Environmental Health.
AB  - Transmission of HIV infection to health care workers in the work place through
      percutaneous or mucocutaneous exposure to blood or blood stained fluid remains
      rare, but it is important for countries to publish updates of cases of HIV
      infection thought to be occupationally acquired. The last update for the United
      Kingdom (UK) summarised data to the end of 1992; this paper summarises cases
      reported to have occurred by June 1997. Four HIV infections classified as
      'definite' occupational acquisitions had been reported in the UK by 1993. No
      further cases in this category have been reported since, but the number of
      "possible" occupationally acquired cases has risen from six to eight. Seven of
      the 12 definite and possible cases reported worked as nurses, four were doctors
      (of whom two were surgeons), and one was a phlebotomist. Seven of the
      transmissions were thought to have occurred in sub-Saharan Africa. Passive
      reporting of exposures to HIV was replaced by a more active reporting system in
      July 1997 in which occupational health departments are contacted regularly.

PMID- 9644124
TI  - Unusual HIV transmissions through blood contact: analysis of cases reported in
      the United Kingdom to December 1997.
AB  - It is important to establish the likely route of infection for all reported HIV
      infected individuals if the HIV epidemic is to be understood. Investigating
      routes of infection may bring unusual infection routes to light. Steps have been
      taken in the United Kingdom (UK) to establish the likely mode of HIV acquisition
      for everyone reported as infected. If an initial report is incomplete the
      clinician caring for the patient is asked for relevant information. If further
      information is needed, and an interview is feasible and acceptable to both the
      clinician and the patient, information is collected from the patient through face
      to-face semistructured interview. Such follow up has identified 19 cases (among
      34,000 records of individuals with HIV and/or AIDS for which probable routes of
      infection have established) who seem to have acquired HIV infection in unusual
      circumstances. Seven of the 19 cases described in this paper are thought to have
      acquired HIV infection in the UK, two in Spain, and ten in countries with a high
      prevalence of HIV infection. This paper describes the circumstances in which HIV
      transmission is believed to have occurred.

PMID- 9644126
TI  - Whooping cough surveillance in the north west of England.
AB  - The number of whooping cough notifications has declined in recent years, as
      vaccine coverage has recovered from the low levels seen in the 1970s and 1980s.
      Notification of infectious disease is often incomplete, and this study aimed to
      estimate the extent to which whooping cough is undernotified. We included all
      cases of whooping cough occurring in the North West Region between 1 April 1994
      and 31 December 1996, identified by notification, hospital admission data, or
      laboratory reports. By combining the three sources, 1239 cases were identified,
      69.6% of which were notified. The notification rate was 29.6% (131/442) for cases
      admitted to hospital and 45.6% (78/170) for laboratory reported cases.
      Completeness of notification was estimated to be 35.7% (863/2420; 95% confidence
      interval 30.3-43.4%) using the capture-recapture method. The study confirms that
      notification of whooping cough is incomplete and suggests that two thirds of
      cases are not notified.

PMID- 9644125
TI  - Enhanced surveillance of acute symptomatic hepatitis B in England and Wales.
AB  - A prospective incidence study was used to estimate the effect on transmission of
      hepatitis B virus (HBV) in England and Wales of maximising uptake of HBV
      vaccination in patients at risk attending genitourinary medicine (GUM) clinics or
      any medical services. Laboratory based surveillance in 1993 gave an incidence of
      acute symptomatic hepatitis B of 1 case per 100,000 population. Transmission
      through sexual intercourse was twice as common as through injecting drug use.
      Less than 20% of patients with acute HBV infection had attended a GUM clinic
      before their illness, but 42% had had access to other medical services where
      vaccination could have been offered routinely. Sixty per cent of patients' sexual
      partners and 37% of other members of their household had been offered
      vaccination. Compared with universal infant or pre-adolescent vaccination,
      extending the current selective policy to all who attend GUM clinics or any
      medical services would have a limited impact on the incidence of HBV,
      particularly as uptake of three doses of vaccine in adults is likely to be low.

PMID- 9644127
TI  - Molecular characterisation of methicillin resistant Staphylococcus aureus.
AB  - Finer discrimination between strains of methicillin resistant Staphylococcus
      aureus (MRSA) than phage typing can provide is needed to identify and
      characterise spread of infection in outbreaks. This study compares three
      molecular methods with each other and with phage typing. Pulsed field gel
      electrophoresis provides the greatest discrimination, but finer discrimination is
      obtainable by combining methods.

PMID- 9644128
TI  - How well do viruses survive during transport?
AB  - Centralisation of viral diagnostic services offers the potential for cost saving
      in laboratories, but incurs costs for transporting specimens. In a trial of 326
      paired specimens, isolation rates of viruses sent by overnight post and a more
      expensive same-day courier service were similar.

PMID- 9644129
TI  - Progress in the development of Helicobacter pylori strain typing methods.
AB  - Helicobacter pylori is very different from other Gram negative bacteria that
      inhabit the human gastroduodenal tract. Its success in adapting to colonise and
      persist in the stomach is reflected in key features such as unique chemical
      structure and architecture of lipopolysaccharide, sheathed flagella, genomic
      diversity, and potent urease activity. Strain diversity within the species is
      well established and so the challenge is to exploit variations in these features
      for developing relevant epidemiological typing methods.

PMID- 9644130
TI  - A user's guide to producing and interpreting tree diagrams in taxonomy and
      phylogenetics. Part 2. The multiple alignment of DNA and protein sequences to
      determine their relationships.

PMID- 9644131
TI  - Noise at work.
AB  - The word noise implies sound that is loud, disturbing, and unwanted. This article
      reviews what can be done about noisy working environments within the context of
      the established legal framework, as well as on a local practical level.

PMID- 9644133
TI  - [A fast iterative algorithm for adaptive histogram equalization].
AB  - In this paper, we propose an iterative algorthm called FAHE., which is based on
      the relativity between the current local histogram and the one before the sliding
      window moving. Comparing with the basic AHE, the computing time of FAHE is
      decreased from 5 hours to 4 minutes on a 486dx/33 compatible computer, when using
      a 65 x 65 sliding window for a 512 x 512 with 8 bits gray-level range.

PMID- 9644132
TI  - [The development of CTTM-1000 distant electrocardiogram central ambulatory
      monitoring system].
AB  - This article introduces a new electrocardiogam telephone transmitting and central
      ambulatory monitoring (receiving) system, and a device used for monitoring and
      transmitting the user's electrocardiogram. We also give some detailed discussion
      about the real time the flow display of ECG, and the signal preprocessing method
      based on the design of optimum FIR linear phase digital filter for the detection
      of QRS complexes.

PMID- 9644134
TI  - [Research of system reliability on Model NXS X-ray image medical machine].
AB  - In the paper, according to theoretic reliability analysis and experiment
      research, the System Reliability of NXS X-ray image medical machine is studied by
      a new computer digital simulation method. The practical method is mainly
      suggested on its FTA model simulated by algorithm on a computer, then the
      Reliability Probability, MTBF and Structure Importance on the machine are
      obtained. The System Reliability results are discussed in detail finally.

PMID- 9644135
TI  - [The development and efficacy tests for the autoclave indicator tape].
AB  - The paper describes the development and efficacy teats for the autoclave
      indicator tape which has specially effects on temperature of pressure steam, time
      of persistence and air of remainder in the autoclave, and quick, simple and
      advanced charater for indirectly testing the quality of autoclave sterilization.

PMID- 9644136
TI  - [The development of a microcomputerized fetal electrocardiograph].
AB  - A new microcomputerized Fetal Electrocardiograph (FECG) is presented in this
      paper. A two-grade configuration (front-end & back-end) is designed for the
      instrument. The front-end processor is based on a Digital Signal Processor (DSP)
      TMS32010 and the Adaptive Noise Cancelling (ANC) algorithm to extract FECG with
      non-invasive method. The processed results are sent to the back-end personal
      computer for real time display, analysis and record. Clinical tests show the
      instrument is designed smartly and operated easily, and can be applied widely to
      many medical situations.

PMID- 9644137
TI  - [The measurement of eye axial length by ultrasound].
AB  - Ultrasonic biometer is the best method of eye axial length measurement now. In
      this paper, our biometric method is introduced. It can measure the anterior
      chamber depth, lens thickness, vitreous length and axial length automatically,
      which are important to intraocular implant (IOL).

PMID- 9644138
TI  - [A new method and instrument for brainlocal hypothermia].
AB  - A new method and instrument for brainlocal hypothermia have been introduced in
      this paper. The instrument provides hypothermia to cerebral blood circulation by
      using cold probe hyperthemia to body venors blood by using electric heater. So it
      reduces the temperature only local in brain. This therapy system provides a safe
      and successful method for brain protection in wide clinical application, such as
      brain injure emergency, cerebrovascular disease therapy, heart operation etc.

PMID- 9644139
TI  - [The development of hematomanometer auto test instrument].
AB  - This paper introduces the development of hematomanometer auto test instrument of
      a news measurement standard. The hard-ware and soft-ware and the circuit
      structure of it are described in detail.

PMID- 9644140
TI  - [The development of model MI-921A automatic clinical electrotyte analyzer].
AB  - A automatic clinical electrolyte analyzer, which based on ion selective
      electrode, has been developed for the measurement of potassium, sodeum, chloride
      and calcium in serum. In this paper, the analyzer's measuring principle is
      described, its structure and the design of hardware and software are also given.
      The analyzer has features of fast analysis, less sample consumption, high
      accurancy and convenience in operation. Good results has been achieved.

PMID- 9644141
TI  - [The data acquisition and handling system controlled by computer for static
      charge along meridians in human].
AB  - The change of static charge along meridian in human is relation to disease. A
      computer controlled data acquisition used for acpoint static charge detection is
      presented in this paper. This system supplied a practical method for researching
      the relation between disease and static charge along meridians in human.

PMID- 9644142
TI  - [The research and design of a constant flow pump for clinical ultrasonic
      emulsification].
AB  - A constant flow pump for clinical ultrasonic emulsification is developed,
      According to request, its output rotational speed can be continuously changed
      from 0 to 40 revolutions per minute. It can stably infuses emulsion to operating
      area.

PMID- 9644143
TI  - [Design of an digital electrical impedance plethysmograph].
AB  - The design of an digital impedance plethysmograph capable of measuring tissue
      impedance and volume change of the ateries during endsystole is reported, The
      50KHz frequency impedance signal is sampled at its peaks and the envelope is used
      to follow the volume change without phase sensitive demodulator. It makes
      frequency and amplitude of the signal more stable and an improved signal to noise
      ratio.

PMID- 9644144
TI  - [Micro-particle image processing based on an artificial neuron network with fluid
      properties].
AB  - The form of macro-particle is a close successive region in two-valued micro
      particle image, and the detection of microparticles is actually that of close
      successive regions. Accordign to this theory, this paper present a new technique
      for micro-particles detecting based on an artificial neuron network modeled on
      the diffusing behaviour of real visual system, which has fluid properties. The
      results of simulation on computer shew that this method is very effect.

PMID- 9644145
TI  - [The study of DSX-I type microcomputer autometic control injector system].
AB  - This paper studies the propulsive force of injector system controlled by 8031
      single-chip microcomputer for Medical use By using one 8031 single-chip
      microcomputer as a microprocessor, the minimal autometic control system is
      constructed, which turns real-time control into reality. This product is a modern
      appliance used in diagnostic imaging medicine, in design of which the advanced
      instrument and electrical machinery are integrated into a unified structure. The
      clinic data demonstrate that the contrast medium can be injected to patients with
      rapidly and evenly. Dynamic CT Scanning can be intensified at any site of the
      body. x-ray dose exposed and lobour intensity to the operator can be decreased
      greatly, raise working efficiency.

PMID- 9644146
TI  - [The development of x-ray machine mAs tester].
AB  - The numeric readout mAs tester described in this paper has the advantage of
      simple and practical structure. It is suitable for regulations and repairs of x
      ray machine for clinical units.

PMID- 9644147
TI  - [Immunohistochemical study of myoglobin deletion from myocardium in hemorrhagic
      shock].
AB  - Myoglobin (MB) deletion from myocardium in the case of hemorrhagic shock was
      firstly studied by immunohistochemical and morphometry technique. The results
      showed that there were different degrees of segmental deletion of MB from
      myocardium in each case of hemorrhagic shock which has continued over an hour.
      The significance of these changes in forensic medicine are discussed.

PMID- 9644148
TI  - [Analysis and assessment of meperidine and normeperidine concentrations in
      urine].
AB  - In this study, urine concentrations of meperidine and normeperidine after a
      single therapeutic dose of meperidine in 5 healthy volunteers have been measured
      and compared the results to those in meperidine addicts. The results showed that
      there was a significant difference between two groups in the ratio of metabolite
      to parent drug. If can be concluded that the ratio should be aid in making a
      cause of meperidine injection.

PMID- 9644149
TI  - [Traumatic testis injuries in clinical forensic medicine: analysis of 5 cases].
AB  - Five cases of traumatic testis injuries are reported. The effect of the testis
      injuries on penile erectile ability and male fertility is reviewed. The problems
      about the appraisal of the traumatic testis injuries in clinical forensic
      medicine are discussed.

PMID- 9644150
TI  - [Trauma and tumor: a report of 14 cases].
AB  - In the present article, we report 14 cases of patients with different tumors,
      injured or died after a traumatic episode. The relation between trauma and tumor,
      and the associated problems in forensic medicine are discussed.

PMID- 9644151
TI  - [Immunohistochemical study on myoglobin in electrocution].
AB  - We have studied the changes of myoglobin (MB) IN heart muscle cells from eight
      corpses died of electrocution. The changes were compared with that of the heart
      muscle cells died of fall. The results indicated that the immunohistochemical
      changes of Mb were as follows: (1) blocky separate from heart muscle cell; (2)
      drift away into the interval of the heart muscle. The Mb changes were small parts
      of an area separate from heart muscle cells in control. The authors emphasized
      these changes were the characteristics of oxygen deficiency of the heart by
      electrocution.

PMID- 9644152
TI  - [Distribution of clozapine in poisoned rabbits].
AB  - The distribution of clozapine in the body of rabbits died of poison was studied
      by the method of TLC. The concentration of clozapine in blood, urine, bile,
      livers, kidneys, spleen, lungs, hearts and brains were 19.4 +/- 6.9, 50.2 +/-
      12.6, 75.9 +/- 12.5, 25.9 +/- 4.0, 34.0 +/- 4.7, 13.3 +/- 2.2, 20.0 +/- 4.3, 5.0
      +/- 2.3 and 43.6 +/- 43.4 ug/ml or ug/g.respectively. It is concluded that the
      Clozapine be not well-distributed in poisoned rabbits, Blood, bile, urine, liver
      and spleen are better samples for the analysis of clozapine than others.

PMID- 9644153
TI  - [Simultaneous detecting of C3 phenotypes and C3 cleavage by immunofixation].
AB  - The C3 phenotypes and C3 cleavage were simultaneously detected using cellulose
      acetate electrophoris followed by immunofixation and desitometry. Compared to
      crossed-immunoelectro-phoresis, this method has some advantages in resolution
      between different bands and was much more rapid, less expensive and more
      sensitive.

PMID- 9644154
TI  - [Usage of double immuno-enzyme labeled staining method in forensic pathology].
AB  - In this paper we report a kind of double immunoenzyme labelled staining method
      (single enzyme method). The principle of the method is that HPR will show blue
      black color when it meet DAB-CoCL2/H2O2, while it will show brown color as it
      meet DAB/H2O2, two colors constract very remarkably. This method was used to
      detect the antigens of hearts and brains which obtained from forensic autopsy.
      The results showed that the method was sensitive, simple and economical. One of
      the advantages is that the stained sections can keep for a long time. Thus, is
      very practical for forensic pathology.

PMID- 9644155
TI  - [Pathological study in sudden death of primary cardiomyopathy: a report of 19
      cases].
AB  - A series of 19 cases of sudden death caused by primary cardiomyopathy were
      investigated. The problems of diagnosing primary cardiomyopathy were discussed.

PMID- 9644156
TI  - [Analysis of poisoned substances in hair].

PMID- 9644157
TI  - [Ageing changes of the cardiac conduct system].
AB  - This paper reviews the ageing changes of the human cardiac conduction system
      according to the ever published literature. In ageing process, the cardiac
      conduction system shows typical physiological changes: (1) differentiation,
      development and maturation in fetal and postnatal period, (2) reduction of the
      specific conduction cells and the changes of the whole node volumes. (3) fibrosis
      and fat infiltration. It is stressed that while explaining the causes of sudden
      death with the knowledge of cardiac conduction system diseases, the forensic
      pathologist should be able to distinguish the pathological changes from that of
      the normal ageing.

PMID- 9644158
TI  - [A quantitative study on the cells of cochlear nucleus in rats at different
      ages].
AB  - The volume of cochlear nucleus and nucleolus, neural populations were determined
      in rats of three groups aged (1, 2-3, 22-28 months). The study data indicated
      that there is no difference between the volume of cochlear nucleus in the aged
      and adult animals (P > 0.05). Compared with the other two groups, the aged
      animals show a reduction of volume of necleolus of cochlear nucleus neurons (P <
      0.01), a loss of neurons (spherical cell and multipolar cell) (P < 0.01). On the
      other hand, it shows an increase in number for the glial cells in the aged
      animals (48.48%, P < 0.01). Quantitative results of the cell of cochlear nucleus
      were analysed. We suggest that central changes also play an important role in
      presbycusis.

PMID- 9644159
TI  - [Dissociation and culture of primary auditory neurons in postnatal chicken].
AB  - In the present study, a primary culture of auditory neurons in 10-16-day old
      chickens was carried out. We observed the morphologic features of auditory
      neurons at different culturing stages by using phased-contrast and scanning
      electron microscope, and particularly described their growth and developmental
      process. The results indicated that a steady and reliable culturing method
      established here would contribute to the biological research of inner ear in
      vitro.

PMID- 9644160
TI  - [Computed tomography of the anterior ethmoid sinuses and its adjacent structures
      for endoscopic sinus surgery].
AB  - Forty adult cadavers were examined by computed tomography (CT) imaging with
      special attention to the pneumatization of the anterior ethmoid sinus for
      endoscopic sinus surgery. The study of the specimen was done using coronal
      section and axial section, sagittal reconstructed images were obtained from the
      data acquired in the axial plane. The cells of anterior ethmoid sinus were
      classified into four sub-groups, namely, the pre-infundibular cell (appearance
      rate 87.5%), the lateral infundibular cell (82.7%), the post-infundibular cell
      (86.3%) and the bulla cell (100.0%), and the anterior ethmoid sinus was
      classified into two types, namely, intraethmoid type (71.2%) and extraethmoid
      type (28.8%). The results shows that CT can display the sub-group and the type of
      the anterior ethmoid sinus and its adjacent structures clearly. The significance
      of endoscopic sinus surgery was discussed.

PMID- 9644161
TI  - [Carotid body tumor (report of 4 cases)].
AB  - Four cases of carotid body tumor are reported, and the diagnosis and treatment
      are also discussed. We consider that color Doppler flow image and carotid
      angiography, especially digital subtraction angiography, are of great value to
      the diagnosis of carotid body tumor. In addition, the collateral cerebral cross
      flow was promoted preoperatively with the use of compressing exercises of the
      carotid artery, and controlled by transcranial Doppler. This means to provide the
      basis for choosing the operative opportunity and for managing the carotid artery.
      The operative method was dependent on preoperative color Doppler flow image,
      carotid angiography, and relationship between the tumor and the carotid artery
      during operation.

PMID- 9644162
TI  - [Infective factors of adult secretory otitis media].
AB  - There were histories of the upper expiratory tract infection in 49 out of 86
      cases in adult secretory otitis media (SOM). Among them, thirty two cases were
      administrated antibiotics a week ago when the effusions were collected. The
      patient's Eustachian tubes in twenty nine cases were clinically ventilated. The
      endotoxins were positive in 39 out of 86 specimen tested with limulus assay,
      among these specimen, bacteria were cultured from 11 specimen. The data exibited
      that the appearance of the SOM is related to the existence of the infective
      factors in the middle ear cavity. The upper expiratory tract infection before the
      onset of the middle ear effusions is one of the important causes inducing the
      disease. The lower rate of bacteria culture than that of endotoxins is related
      with the administration of antibiotics before the onset of the disease. The
      administration of antibiotics in the treatment of the middle ear effusions will
      help to elimilate bacteria in the cavity of the middle ear effusions, improve the
      ventilating function of the Eustachian tube and make the effusions turn to
      disappearance.

PMID- 9644163
TI  - [Digital subtraction angiography and selective arterial embolization in the
      treatment of vascular tumors in nasopharynx and nasal sinuses].
AB  - The paper presents the treatment of vascular tumors in nasopharynx and nasal
      sinuses with digital subtraction angiography (DSA) and selective arterial
      embolization. By using preoperative embolization of blood supply arteries, the
      intraoperative bleeding was reduced significantly, the tumors were shrank and the
      tumor limits were clear. We recommend that DSA and selective arterial
      embolization should be used as a routine preoperative method adjunct to surgery
      for the treatment of vascular tumors of nasopharynx and nasal sinuses.

PMID- 9644164
TI  - [Study of the expression of the epidermal growth factor-receptor in the laryngeal
      squamous cell carcinoma and the correlation with clinical pathology
      characteristics].
AB  - OBJECTIVE: The expression of the epidermal growth factor-receptor (EGF-R) in the
      laryngeal squamous cell carcinoma and the correlation with clinical
      characteristics of the tumor, difference of tissues. METHOD: Immunohistochemical
      detection. RESULTS: The EGF-R expression was evaluated in 36 laryngeal squamous
      cell carcinoma and 25 normal laryngeal tissues specimens. The EGF-R expression
      showed only in one specimen of normal laryngeal tissues, whereas twenty-four of
      thirty-six carcinomas showed positive staining reaction with the anti EGF-R
      antibodies. The EGF-R expression did not correlate with age, whereas it was
      higher in poorly differentiated tumors than in moderately and well differentiated
      tumors (P < 0.05) and it was higher in T3, 4 of TNM classification than in T1, 2
      (P < 0.05). Four patients being the recurrence cancers after the operation had an
      enhanced expression of EGF-R. Six of seven patients with the metastatic
      cervicallymph-node involvement showed an enhanced expression of EGF-R.
      CONCLUSIONS: The uncontrolled cell growth and proliferation of the laryngeal
      squamous cell carcinomas may be related to the abnormal EGF-R expression. The
      enhanced expression of EGF-R can be identified as a poorly prognostic parameter.

PMID- 9644165
TI  - [The treatment of nasopharyngeal carcinoma by using thermoradiotherapy].
AB  - The treatment effect of radiotherapy combined with local hyperthermia for
      nasopharyngeal carcinoma was studied in 23 patients. In 24 cases of the control
      group (radiotherapy), conventionally dynamic fractionation of dose was used. At
      40 Gy, the regression of tumor was observed 83% in the study group and 54% in the
      controls group. No severe complications in patients treated by thermotherapy were
      noted. This paper discusses the role and the mechanism of local hyperthermia as a
      rediomodifying factor.

PMID- 9644166
TI  - [Study of optimal parameters and normal values for auditory P300].
AB  - Study of optimum seeking method with orthogonal test for auditory P300 measuring
      was carried out in healthy adolescents. The result showed that the optimal
      conbination of parameters was as follows: stimulus sound was Logon, recording
      electrode site Cz, analysis time 750 ms, average 100, stimulus rate 1 c/s, target
      stimulus (TS) probability 10%, bandpass filter 1-50 Hz, non-target stimulus (NTS)
      freqency 1 kHz, target stimulus (TS) frequency 2 kHz, stimuli intensities 110 dB
      peSPL. The normal values of auditory P300, obtained from 30 healthy adolescents,
      including latencies and amplitudes, were measured under optimal parameters. P300
      latency was about 310 ms, RT about 258 ms, these two values present a significant
      linear correlation.

PMID- 9644167
TI  - [Study on the relation between HPV and tumors of the throat and larynx].
AB  - HPV structural antigens and HPV 6, 11, 16, 18 DNA sequences were detected with
      immunohistochemical staining and DNA dot blot hybridization in papillomas and
      squamous cell carcinomas of the throat and larynx. The positive rates of HPV
      antigens and HPV DNA sequences in 11 cases of papillomas were 45.5%,
      respectively, while the positive rates of HPV in 22 cases of squamous cell
      carcinomas were 22.7% and 27.3% respectively. The positive rates of HPV were in
      accord with those by histologic study in papilloma. The results indicate that the
      papillomas and squamous cell carcinomas of the throat and larynx may be related
      with HPV infection.

PMID- 9644168
TI  - [The relationship between histologic grading of malignancy and regional lymph
      node metastasis in squamous cell carcinoma of larynx].
AB  - Forty cases of squamous cell carcinoma of larynx have been studied by using five
      factors scale in order to investigate the relation between histologic grading of
      malignancy and regional lymph node metastasis. The results show that high degree
      malignancy tumor (which gets more than ten points) and diffusly invased tumor
      have a significantly higher proportion of regional lymph node metastasis than
      others. There was no relation between histologic grading of malignancy and T
      categories. It indicated that histologic grading of malignancy may be a good help
      in predicting patient evolution.

PMID- 9644169
TI  - [Hyaluronic acid-streptomycin perfusion of the labyrinth through the round
      window].

PMID- 9644170
TI  - [Distortion product otoacoustic emissions on neonates].
AB  - Distortion product otoacoustic emissions (DPOAE) is evoked by two pure-tones (f1,
      f2). It is a kind of reflex of cochlea. In order to know the effect of different
      elements on DPOAE of neonates, we used GSI 60 DPOAE to detect the DPOAE of 40
      ears of 20 neonates. The results showed that when f1 was below 1,000 Hz, the
      incidence of DPOAE was very low. When the f1 was between 1,400 and 4,000 Hz, the
      incidence of detectability was more than 90%. The amplitude of DPOAE was low
      within lower frequency area, while f1 was between 1,000 and 4,000 Hz, the
      amplitude was higher. We consider that the DPOAE of neonates were easily affected
      by noise, stimulus intensity, the function of middle ear, etc. We must pay
      attention to these elements when we use DPOAE to test hearing function of
      neonates.

PMID- 9644171
TI  - [Mondini's deafness].
AB  - Mondini's deafness was the congenital malformation of inner ear. We studied 199
      ears of 106 cases. Most of them were found deaf when they were babies. High
      resolution computed tomography of temperal bone was described: cochlea
      malformation 4 ears; malformation of cochlea, vestibule and semicircular canal 90
      ears; vestibular of semicircular malformation without cochlea malformation 105
      ears, this type was called the vestibule malformation or untypically Mondini's.
      Of all the 199 ears there were 81 ears with enlargement of the vestibule
      aqueducts. The pathogeny, clinical manifestation and treatment were discussed.

PMID- 9644172
TI  - [Cross susceptibility of ototoxicity about aminoglycoside antibiotics].
AB  - A familial investigation was made in three families with deafness patients caused
      by aminoglycoside (AMI). The results showed that there was cross susceptibility
      among a few AMI antibiotics. The people with familial history of deafness caused
      by AMI were easier to be toxic than those without familial history, even though
      little dose of AMI for the former, especially for children. The cross
      susceptibility is dominated by inheritance of matriarchal heredity and by general
      chromosome. The data suggest that medical history should be inquired before
      treatment with AMI, and patients with matriarchal heredity must be prohibited
      from using AMI.

PMID- 9644173
TI  - [Application of otoadmittance to measure eustachian tube tympanometry].
AB  - This paper studied a simplified and quantified valsalva and reverse valsalva
      maneuver eustachian tube tympanometry with otoadmittance meter. In normal groups,
      the compliance changes were 0.57 +/- 0.23 ml with valsalva maneuver and 0.26 +/-
      0.12 ml with reverse valsalva maneuver. Otherwise, the recordings were performed
      in various tympanic functions induced by various eustachian tube functions, and
      the results showed that this method was significant for the diagnosis of
      eustachian tube structure, obstruction or patency. The recording curves helped to
      determine the types and degrees of eustachian tube abnormality.

PMID- 9644174
TI  - [Intranasal endoscopic ethmoidectomy and the analysis of curative effect].
AB  - Forty cases of intranasal endoscopic ethmoidectomy were analyzed. In this series,
      28 males and 12 females were included. Hard endoscopes with diameter of 4 mm,
      visual angle 30 and 70 were used. All patients were followed-up for 3 to 12
      months. The surgical results were that twenty percent of patients were completely
      relieved of symptoms, 10% symptom-free with additional therapy, 40% improved
      without additional therapy, 20% improved with additional therapy, 10% no
      improvement and the total effective rate was 90%. No operative complications
      happened. Some factors affecting operative effects were discussed.

PMID- 9644175
TI  - [Endoscopic sinus surgery through the front wall of maxillary sinus: report on 30
      cases].
AB  - By drilling the front wall of maxillary sinus, endoscopic sinus surgery was
      performed in 30 cases. Using this method, the focus was easily observed and
      cleaned, the natural hole was rapidly and reliably reamed with less bleeding and
      no serious reaction, and the rate of recurrence was lower.

PMID- 9644176
TI  - [Tumours of the nose and sinuses presented as nasal polyp].
AB  - Twelve cases of tumours of the nose and sinuses misdiagnosed at the first time as
      nasal polyp are reported. Of them, 4 were benign and 8 malignant. The endoscopic
      technique is helpful to differential diagnosis of benign or malignant lesions and
      polyps in these areas.

PMID- 9644177
TI  - [Embryogenesis and functional development of the chick's basilar papilla].

PMID- 9644178
TI  - [The application of transmeatal exploratory tympanotomy].
AB  - Transmeatal exploratory tympanotomy has been used traditionally for the surgical
      treatment of conductive deafness. With 8 cases of the middle and inner ear
      diseases diagnosed and surgical managed successfully with this approach, the
      extended applications of this procedure were illustrated, which included: 1.
      conductive deafness with cause undetermined, 2. post traumatic conductive
      deafness with intact tympanic membrane, 3. suspected primary space occupying
      lesion of tympanum. 4. perilymphatic fistula, and 5. cerebrospinal fluid
      otorrhea. The key consideration and advantage of this approach were also
      discussed in this paper.

PMID- 9644179
TI  - [Malignant changes in laryngeal papilloma with 13 case reports].
AB  - The 13 cases of malignant changes in 43 cases of laryngeal papilloma are
      reported. The rate of malignant change was 30. 2%. Laryngeal papilloma with
      epithelial atypia has proclaimed the onset of carcinoma. Therefore, high
      attention should be paid on its treatment. The safe margin on the operation of
      the malignant change case should be kept above 0.5 cm and radiation should be
      followed after the operation. It was invalid by using only radiation treatment.
      The pathogenesis and diagnosis of malignant change in laryngeal papillomas were
      also discussed in this article.

PMID- 9644180
TI  - [The use of platysmal myocutaneous flaps in laryngeal reconstruction].
AB  - Vertical frontal subtotal laryngectomy, a procedure that can remove as much as
      90% of the larynx, was used to produce a functionally acceptable neolarynx with
      platysmal myocutaneous flaps. Thirty-two patients with laryngeal carcinoma
      underwent this operation. All flaps survived and there was no necrosis after
      operation. With the exception of one patient who require nasal feeding because of
      an irritating cough when swallowing food, all the other patients regain
      breathing, swallowing and phonating of laryngeal function. The operative methods,
      advantages and experiences are discussed in this paper.

PMID- 9644181
TI  - [Determination of complements in serum and middle ear effusion of the patients
      with secretory otitis media].
AB  - Complements in serum and middle ear effusion were determined in 20 patients with
      secretory otitis media, and compared with those in the normal controls. The C5
      and C1-INH in serum of the patients were significantly higher. On the contrary,
      C9 and B factor (Bf) were significantly lower, and the circulatory immunocomplex
      was also higher. In patients with secretory otitis media, the middle ear effusion
      levels of C3, C4 and C5 were significantly lower, and Bf and immunocomplex were
      significantly higher than those in serum. The results suggest that the ability of
      complements in clearing immunocomplex is low. Therefore, the immunocomplex may
      deposit in the mucosa of the middle ear. Thus the permeability of capillary will
      be increased, and the middle ear effusion occurs.

PMID- 9644182
TI  - [Ultrastructural study of tumor infiltrating lymphocyte in tissues of laryngeal
      squamous cell carcinoma].
AB  - By transmission electron microscopy tumor infiltrating lymphocyte (TIL) in
      laryngeal squamous cell carcinoma tissues of 14 cases was studied. The results
      showed that the infiltrating lymphocyte in varying degrees eristed in laryngeal
      squamous cell carcinoma tissues. Most of them were present in a motionless state,
      and the others showed the feature of activated metrocyte and closely contracted
      with cancer cells and resulted in distinct morphological changes both the cancer
      cells and themselves. Therefore, this study provided an important morphological
      evidence for TIL as killer and inhibiter to the growth of cancer cells.

PMID- 9644183
TI  - [Kaposi's sarcoma associated with HIV in otorhinolaryngology: report of 21
      cases].
AB  - Twenty one cases of kaposi's sarcoma (KS) with manifestation in the field of
      otolaryngology are reported. The incidence of KS is increasing following epidemic
      of AIDS all over the world. Epistaxis, nasal obstruction, sore-throat, dry of
      foreign body filling in throat and nodal mass are most frequent manifestation.
      The relationship of KS with HIV, it's pathology and diagnosis are discussed.

PMID- 9644184
TI  - [Effect of human recombinant gamma-interferon on proliferative activity of human
      laryngeal cancer cell lines].
AB  - The effect of human on PCNA expressions of HEP-2 lines was investigated using
      LSAB (Labelled streptacidin biotin method) with monoclonal antibody Ki-67 (anti
      PCNA). The results showed that the PCNA expression which reflects the
      proliferative activity of cells was dependent on dose of rhu-IFN-gamma in HEP-2
      cell lines. Thus, our data suggest that rhu-IFN-gamma might be useful in the
      treatment of laryngeal cancer because it provides effective cytostatic.

PMID- 9644185
TI  - [Study on the immune state of patients with laryngeal carcinoma].
AB  - The authors have carried out the immunoassay on 68 patients with laryngeal
      carcinoma in order to investigate the relationship between the occurrence and
      development of the tumour and the body immune state by using the methods of R1D,
      APAAP and LDH. The results showed that, in comparison with the normal group,
      CD3+, CD4+ cell and NK cell activity were much lower (P < 0.01), CD8+ cell
      slightly increased (P > 0.05). IgG, IgA and IgM were also lower (P < 0.05). It
      indicates that the lower level of cellular immunity, the descent of the ratio of
      CD4+/CD8+ and the condition which suppresses the body immune system are the
      interior factors which make the laryngeal carcinoma happening and developing
      easily. With the development of tumor, the increase of various suppressor factors
      and the immune system suppressed further the tumor can spread and shift much more
      easily.

PMID- 9644186
TI  - [Suppressor gene p16 and head and neck tumors].

PMID- 9644187
TI  - A creeping suspicion about radon.

PMID- 9644188
TI  - Radio-free America: what to do with the waste.

PMID- 9644189
TI  - Two steps forward on environmental justice.

PMID- 9644190
TI  - Alternatives to Incineration: There's More Than One Way to Remediate.

PMID- 9644191
TI  - Transgenic approaches for modifying the mammary gland to produce therapeutic
      proteins.
AB  - Bioengineering of the mammary gland to produce proteins of therapeutic and
      industrial value is the result of extensive investigation of the physiology of
      the mammary gland and the ability to generate transgenic animals. Targeting the
      expression of heterologous proteins to mammary tissue requires a thorough
      understanding of the biochemical events that coordinate growth and
      differentiation of the mammary gland and of the hormonal and developmental
      regulation of expression of milk protein genes. The characterization of mammary
      specific promoter regions in milk protein genes and knowledge of the mechanisms
      that confer integration site-independent expression of transgenes have
      significantly contributed to modifying the mammary gland to produce heterologous
      proteins of therapeutic interest. The generation of large transgenic farm animals
      provides the opportunity for large-scale production of proteins in milk that have
      a therapeutic value but are naturally present at low concentrations in biological
      fluids. Transgenic mammary epithelial cells offer a versatile research model in
      biomedical, environmental health, and neonatal toxicology research.

PMID- 9644192
TI  - The cytochromes P450 and mechanisms of chemical carcinogenesis.
AB  - This article reviews mechanisms of chemical carcinogenesis, from metabolic
      activation and generation of reactive oxygen species by cytochromes P4511 and
      P4502E to DNA damage, activation of protein kinase C and ocogenes, hyperplasia,
      and proteoglycan changes in the cell glycocalyx and lysosomal enzymes which
      mediate invasion and metastasis.

PMID- 9644193
TI  - Health concepts, issues, and experience in the Abakaliki area, Nigeria.
AB  - Environmental health problems are increasingly receiving global attention. The
      health of entire nations may not only be affected by adverse environmental
      conditions, but by nutritional deficiencies that lead to morbidity and mortality.
      The type and extent of adverse health effects in a population depend on the
      potential for exposure to some environmental factors and pathogens as well as
      other environmental variables like industrialization, sanitation conditions, and
      urbanization. National and international comparisons between health status
      indicators can reveal the extent of any differences that exist, including dynamic
      changes in prevailing environmental conditions which may be helpful in
      characterizing the role of specific risk factors. Improvements in collection of
      environmental data related to health can help to identify, control, and eliminate
      many of the factors that are associated with environmental risk in the Abakaliki
      area of eastern Nigeria.

PMID- 9644194
TI  - Nitrite inhalants: history, epidemiology, and possible links to AIDS.
AB  - Nitrite inhalants have been commonly abused substances in the United States.
      Nitrite inhalants and AIDS was a popular topic in the early 1980s, when the cause
      of AIDS was not known. With the discovery of HIV, concern about nitrite use in
      the USA waned. However, nitrite inhalant use is associated with behavioral
      relapse and HIV transmission among gay men, with decreased lymphocyte counts and
      natural killer cell activity in a few laboratory studies, and it remains a
      candidate cofactor in the pathogenesis of AIDS-related Kaposi's sarcoma.
      Discouraging nitrite use continues to be a worthwhile public health goal.

PMID- 9644195
TI  - Characterization by scanning transmission electron microscopy of silica particles
      from alveolar macrophages of coal miners.
AB  - The structure and composition of silica-rich particles recovered by lavage from
      the lungs of three active miners with different medical histories were studied
      using high-resolution electron microscopy and chemical microanalysis. The results
      are compared to the similarly determined structure and composition of respirable
      size mineral particles obtained from roof-bolter dust-box samples from two coal
      mines of widely different bulk quartz concentrations. The results show that the
      lungs of the miners contain silica-based particles with structures not found in
      the mine samples. Also, the particle structures and compositions found in the
      macrophages were different in each of the miners. The results suggest that
      possibility that intracellular processes may affect the susceptibility of
      individuals to silica-induced pneumoconioses.

PMID- 9644196
TI  - Environmental tobacco smoke is just as damaging to DNA as mainstream smoke.
AB  - This study demonstrates the ability of tar isolated from environmental tobacco
      smoke (ETS) to nick DNA in mammalian cells. Solutions of ETS tar behave similarly
      to aqueous solutions of cigarette tar from mainstream smoke. Both solutions
      contain the tar semiquinone radical, and this radical associates with the DNA in
      viable rat alveolar macrophages. Solutions of tar from ETS cause single-strand
      DNA breaks in rat thymocytes in proportion to the amount of tar present, until a
      plateau is reached. ETS tar solutions, like mainstream tar solutions, produce
      hydrogen peroxide. Hydrogen peroxide appears to be an essential component of the
      mechanism by which both ETS tar and mainstream tar cause DNA damage in rat
      thymocytes, as catalase substantially protects against DNA damage. Glutathione
      also protects against DNA nicking by both ETS and mainstream tar solutions by
      scavenging radicals and/or oxidants. The chelator diethylenetriamine pentaacetic
      acid also provides partial (40%) protection. The studies demonstrate that the
      water-soluble components of ETS tar can enter cells, associate with, and then
      nick DNA.

PMID- 9644197
TI  - Changes in serial blood lead levels during pregnancy.
AB  - The first step in modeling lead kinetics during pregnancy includes a description
      of sequential maternal blood lead (PbB) during pregnancy and the factors
      controlling it. We analyzed PbB of 105 women living in the Valley of Mexico from
      week 12 to week 36 of pregnancy and again at parturition. We also used data from
      all women contributing blood at any stage of pregnancy to determine antecedents
      of PbB. Pregnancies were uneventful, and offspring were normal. Although
      geometric mean PbB level averaged around 7.0 micrograms/dl (0.34 mumol/l), with a
      range of 1.0-35.5 micrograms/dl throughout pregnancy, analysis of variance
      revealed a significant decrease in mean PbB from week 12 to week 20 (1.1
      micrograms/dl) and various significant increases in mean PbB from week 20 to
      parturition (1.6 micrograms/dl). Regression analyses confirmed the positive
      linear PbB trend from 20 weeks to parturition and additional contributions of
      dietary calcium, reproductive history, lifetime residence of Mexico City, coffee
      drinking, and use of indigenous lead-glazed pottery. Although decreasing
      hematocrit has been suggested to explain first-half pregnancy PbB decrease, the
      time course of hematocrit decrease in the present study did not match the
      sequential changes in PbB. While hemodilution and organ growth in the first half
      of pregnancy may account for much of the PbB decrease seen between 12 and 20
      weeks, the remaining hemodilution and accelerated organ growth of the last half
      of pregnancy do not predict the trend toward increasing maternal PbB
      concentration from 20 weeks to delivery. Mobilization of bone lead, increased gut
      absorption, and increased retention of lead may explain part of the upward PbB
      trend in the second half of pregnancy. Reduction of lifetime lead exposure may be
      required to decrease risk of fetal exposure.

PMID- 9644201
TI  - The manganese superoxide dismutase from the penicillin producer Penicillium
      chrysogenum.
AB  - The antioxidant enzyme superoxide dismutase has been studied in order to define
      mechanisms for the influence of oxygen on penicillin production. Manganese
      containing SOD activity was purified from penicillin-producing cultures of the
      filamentous fungus Penicillium chrysogenum and reverse genetics was used to
      identify full-length cDNA and genomic clones. Sequence analysis revealed a 630-bp
      ORF containing three exons and two introns with fungal consensus splice-site
      junctions. The deduced amino-acid sequence (210 amino acids; 23.13 kDa) includes
      conserved residues required for enzymatic activity and metal binding, and shares
      significant similarity with Mn- and Fe-containing superoxide dismutases. The sod
      gene is present as a single copy in the genome of different P. chrysogenum
      strains and its expression level is not correlated with penicillin-G
      productivity.

PMID- 9644202
TI  - Functional analysis of different regions of the positive-acting CYS3 regulatory
      protein of Neurospora crassa.
AB  - In the filamentous fungus Neurospora crassa during conditions of sulfur
      limitation, CYS3, a major positive-acting regulatory protein, turns on the
      expression of an entire set of genes which encode permeases and enzymes involved
      in the acquisition of sulfur from environmental sources. CYS3 functions as a
      homodimeric protein and possesses a b-Zip domain that confers sequence-specific
      DNA binding. Expression of various hybrid GAL4-CYS3 fusion proteins in yeast was
      used to detect regions involved in gene activation. An amino-terminal
      serine/threonine-rich domain of CYS3 alone strongly activated expression of beta
      galactosidase, the yeast reporter. Moreover, mutant CYS3 proteins with amino-acid
      substitutions in this region that showed increased expression in Neurospora also
      displayed an enhanced activation potential in yeast. The cys-3 gene of the exotic
      N. crassa Mauriceville strain and of N. intermedia were cloned and demonstrated
      to be functional for gene activation and for sulfur-mediated regulation by
      complementation of a loss-of-function cys-3 mutation. The amino-terminal
      serine/threonine-rich region is highly conserved in these two CYS3 proteins, in
      agreement with the possibility that it serves as the activation domain.
      Surprisingly, an extended promoter region of the cys-3 gene in the Mauriceville
      strain and in N. intermedia was very well conserved with that of the standard N.
      crassa gene, including the presence of three CYS3-binding sites possibly involved
      in autogenous control. Results are presented which indicate that synthesis of the
      CYS3 regulatory protein is highly regulated and can be detected in the nucleus of
      cells subjected to sulfur de-repression, but is not found in the nucleus or the
      cytoplasm of S-repressed cells. The amino-acid substitutions of the CYS3 protein
      present in a temperature-sensitive cys-3 mutant and in a second-site revertant of
      a cys-3 null mutation are presented and are shown to affect their DNA-binding
      activities.

PMID- 9644203
TI  - Functional analysis of upstream activating elements in the promoter of the FBP1
      gene from Saccharomyces cerevisiae.
AB  - We have investigated the effect of different carbon sources and of different
      mutations on the capacity of two elements, UAS1 and UAS2, from the promoter of
      the FBP1 gene to form specific DNA-protein complexes and to activate expression
      of a reporter gene. The complexes are observed with nuclear extracts from yeast
      derepressed on glycerol or ethanol. When hxk2 mutants are grown on glucose the
      nuclear extracts are able to complex UAS1 but not UAS2, while for wild-type cells
      grown on galactose only the complex with UAS2 is formed. In contrast, in vivo the
      operation of both UASs is high in ethanol, moderate to low in glycerol, and
      negligible in galactose; no expression is observed in glucose even in a hxk2
      background. There is no effect of a MIG1 deletion, either in the formation of DNA
      protein complexes or on the expression of reporter genes.

PMID- 9644204
TI  - Isolation of UBP3, encoding a de-ubiquitinating enzyme, as a multicopy suppressor
      of a heat-shock mutant strain of S. cerevisiae.
AB  - Yeast strains lacking functional copies of the two genes SSA1 and SSA2, which
      encode cytosolic molecular chaperones, are temperature-sensitive. In this report,
      we describe the isolation of a high-copy suppressor of this temperature
      sensitivity, UBP3, which encodes a de-ubiquitinating enzyme. We show that ubp3
      mutant yeast strains have a mild slow-growth phenotype and accumulate ubiquitin
      protein conjugates. We propose a model in which Ubp3p acts in vivo to reverse the
      ubiquitination of substrate proteins, allowing temporarily misfolded proteins an
      opportunity to fold correctly.

PMID- 9644205
TI  - Editing status of mat-r transcripts in mitochondria from two plant species: C-to
      U changes occur in putative functional RT and maturase domains.
AB  - The intronic mat-r ORF encodes a protein with significant homology to retroviral
      reverse transcriptases. Here, we describe the nucleotide sequence of potato mat-r
      and study the editing status of mat-r transcripts in two systems, potato and
      wheat, where the mat-r ORF is part of the trans-introns but in two different
      configurations relative to nad1 exons d and e. In potato and wheat, 13 and 15 C
      to-U transitions respectively were observed. Most transcripts were partially
      edited, but potato transcripts were edited more efficiently than wheat
      transcripts. As in functional mitochondrial genes, RNA editing increased the
      similarity between plant mat-r proteins and their homologous non-plant
      counterparts. Interestingly, editing of mat-r was clustered in the reverse
      transcriptase (RT) and the maturase (X) domains, two well defined regions having
      known functions in other systems. These results, together with the integrity and
      sequence conservation of mat-r, strongly suggest that the encoded protein plays a
      functional role in plant mitochondria.

PMID- 9644206
TI  - Interaction of mitochondrial RNA editing and nucleolytic processing in the
      restoration of male fertility in sorghum.
AB  - Nucleolytic processing of transcripts within mitochondrial orf107, associated
      with male sterility in sorghum, is regulated by the fertility restoration gene
      Rf3, conferring 75% cleavage of whole-length transcripts. Two transcript editing
      sites are 81% and 61% edited in rf3rf3 lines, while these sites are 41% and 10%
      edited in the remaining whole-length transcripts in an Rf3Rf3 line. RNA editing
      and processing efficiency in F1 progeny were similar to the Rf3Rf3 parent, and
      analyses of backcross progeny indicated that all rf3rf3 lines were characterized
      by high editing efficiency. We postulate that highly edited transcripts within
      the population are quickly processed in lines carrying Rf3, generating a residual
      population of poorly edited transcripts. Thus, action of Rf3 may have no direct
      affect on RNA editing, and may be dependent on a substrate of highly edited
      transcripts. These data indicate a potentially novel role of RNA editing in gene
      expression through an influence on the efficiency of transcript processing.

PMID- 9644207
TI  - Differential changes in copy numbers of rice mitochondrial plasmid-like DNAs and
      main mitochondrial genomic DNAs that depend on temperature.
AB  - The mitochondria of rice contain four kinds of circular plasmid-like DNAs,
      namely, B1, B2, B3 and B4, in addition to the main mitochondrial genomic DNAs. In
      order to examine the genetic stability of mitochondrial plasmid-like DNAs,
      changes in the amounts of plasmid-like DNAs and main mitochondrial genomic DNAs
      were analyzed in calli that had been cultured at various temperatures. The
      observed effect of temperature on the levels of plasmid-like DNAs was larger than
      that on the main mitochondrial genomic DNAs. A significant reduction in the copy
      number of plasmid-like DNAs was detected in calli cultured at 35 degrees C, as
      compared to 20 degrees C, 25 degrees C and 30 degrees C. The effect of
      temperature on DNA synthesis in isolated mitochondria was also analyzed.
      Synthesis of the main mitochondrial genomic DNAs occurred at all the temperatures
      examined, whereas synthesis of plasmid-like DNAs occurred only over a limited
      range of temperatures. The results of both in vivo and in vitro analyses suggest
      that plasmid-like DNAs are less stably maintained than the main mitochondrial
      genomic DNAs, which is consistent with the notion that the transmission of
      mitochondrial plasmid-like DNAs from one generation to the next may be unstable
      under unusual conditions.

PMID- 9644208
TI  - Isolation of a Trichoderma reesei cDNA encoding GTP: a-D-mannose-1-phosphate
      guanyltransferase involved in early steps of protein glycosylation.
AB  - A cDNA coding for GTP: alpha-d-mannose-1-phosphate guanyltransferase (MPG1
      transferase) (EC 2.7.7.13) was isolated from a cDNA library of the Trichoderma
      reesei RutC-30 strain by suppression of the yeast Saccharomyces cerevisiae
      mutation in the DPM1gene encoding mannosylphosphodolichol (MPD) synthase. The
      nucleotide sequence of the 1.6 kb-long cDNA revealed an ORF which encodes a
      protein of 364 amino acids. Sequence comparisons demonstrate 70% identity with
      the S. cerevisiae guanyl transferase gene (MPG1) and 75% identity with the
      Schizosaccharomyces pombe homologue. No similarity was found with the MPD
      synthase encoded by the S. cerevisiae DPM1 gene. The possibility that cloned cDNA
      encodes a product with a MPD synthase activity was also excluded by transforming
      a heterozygous S. cerevisiae dpm1::LEU2/DPM1 diploid, which did not lead to the
      restoration of viability of the dpm1 spores. Simultaneously, a significant
      increase in MPG transferase activity, as compared with the wild-type yeast, was
      observed in cellular extracts when the mpg1 cDNA from Trichoderma was expressed
      in the S. cerevisiae dpm1-6 mutant.

PMID- 9644209
TI  - Candida albicans ALS3 and insights into the nature of the ALS gene family.
AB  - The ALS1 (agglutinin-like sequence) gene of Candida albicans encodes a protein
      similar to alpha-agglutinin, a cell-surface adhesion glycoprotein of
      Saccharomyces cerevisiae (Hoyer et al. 1995). A central domain of a tandemly
      repeated 108-bp sequence is found in the ALS1 coding region. This tandem-repeat
      motif hybridizes to multiple C. albicans genomic DNA fragments, indicating the
      possibility of other ALS1-like genes in C. albicans (Hoyer et al. 1995). To
      determine if these fragments constitute a gene family, tandem-repeat-hybridizing
      genomic fragments were isolated from a fosmid library by PCR screening using
      primers based on the consensus tandem-repeat sequence of ALS1 (Hoyer et al.
      1995). One group of fosmids, designated ALS3, encodes a gene with 81% identity to
      ALS1. The sequences of ALS1 and ALS3 are most conserved in the tandem-repeat
      domain and in the region 5' of the tandem repeats. Northern-blot analysis using
      unique probes from the 3' end of each gene demonstrated that ALS1 expression
      varies, depending on which C. albicans strain is examined, and that ALS3 is
      hyphal-specific. Both genes are found in a variety of C. albicans and C.
      stellatoidea strains examined. The predicted Als1p and Als3p exhibit features
      suggesting that both are cell-surface glycoproteins. Southern blots probed with
      conserved sequences from the region 5' of the tandem repeats suggest that other
      ALS-like sequences are present in the C. albicans genome and that the ALS family
      may be larger than originally estimated.

PMID- 9644210
TI  - Dihydropyridine receptor isoform expression in adult rat skeletal muscle.
AB  - The expression of isoform-specific dihydropyridine receptor Ca2+ channel (DHPR)
      alpha1-subunit genes in rat diaphragm, soleus and extensor digitorum longus
      muscles was investigated using RNase protection assays. As expected, mRNA
      expression levels for the DHPR skeletal muscle isoform were highest in extensor
      digitorum longus. Unexpectedly, both diaphragm and soleus expressed mRNA for the
      cardiac isoform at a significant level. Moreover, immunohistochemical experiments
      provided evidence of the cardiac DHPR isoform at the protein level in muscle
      fibres. The presence of the cardiac DHPR in the soleus and diaphragm is
      consistent with a degree of reported cardiac-like excitation-contraction coupling
      in these muscles, and may be an explanation for some of the therapeutic effects
      of theophylline in asthmatics, but is likely to serve some other role(s) as well.

PMID- 9644211
TI  - Involvement of deoxygenation-induced increase in tyrosine kinase activity in
      sickle cell dehydration.
AB  - Deoxygenation of sickle (SS) cells causes cationic alterations leading to cell
      dehydration by various mechanisms, including activation of Ca2+-sensitive K
      channels and possibly of K-Cl cotransport. Since an abnormal tyrosine kinase (TK)
      activity exists in SS cells we investigated the possible role of tyrosine
      phosphorylation in SS cell dehydration. In density-fractionated SS reticulocytes
      and discocytes, but not in normal red cells, deoxygenation increased membrane and
      cytosolic TK activities and tyrosine phosphorylation of band 3, independently of
      external Ca2+. These effects were abolished by the TK inhibitors methyl 2, 5
      dihydroxycinnamate (DiOH) or tyrphostin 47 (T47). Deoxygenation-induced Ca2+
      uptake was not affected by the inhibitors and Na+ gain was reduced by T47 and not
      by DiOH. Both inhibitors decreased the loss of K+ and cellular dehydration. The
      effect of the inhibitors on K+ efflux was still observed in the absence of
      external Ca2+. These data indicate that the TK inhibitors do not interfere with
      deoxygenation-induced membrane permeabilization, but affect Ca2+-independent K+
      efflux. It cannot be excluded, however, that the TK inhibitors also attenuate
      Ca2+-sensitive K+ efflux. Based on recent evidence from the literature, it is
      suggested that the diminution of K+ efflux results in part from inhibition of K
      Cl cotransport activity.

PMID- 9644212
TI  - Positive feedback regulation of angiotensin II-AT1B receptor gene expression in
      rat adrenal glands.
AB  - This study aimed to investigate the role of endogenous angiotensin II (ANGII) in
      the upregulation of ANG-II AT1 receptors in adrenal glands during a low-salt
      intake. To this end male Sprague-Dawley rats were fed a low-salt diet (0.2 mg/g)
      for 10 days and were treated with the ANGII-AT1 receptor antagonist losartan (40
      mg/kg per day) for 2 days, and adrenal mRNA levels for ANGII AT1A and AT1B
      receptors were determined by RNase protection. The low-salt diet increased AT1A
      and AT1B receptor mRNA levels by 90% and 220%, respectively. Losartan treatment
      did not change the basal AT1A mRNA level, but decreased AT1B mRNA by 50%.
      Treatment of rats on a low-salt diet with losartan did not change the increase of
      AT1A mRNA but significantly attenuated the increase of AT1B mRNA to 90% of the
      control value. Stimulation of endogenous ANGII levels by unilateral renal artery
      clipping for 2 days lowered AT1A mRNA by 25% and increased AT1B mRNA by 30%.
      Additional treatment with losartan did not affect the decreased AT1A mRNA levels
      in rats with a unilateral renal artery clip, but significantly attenuated the
      increase of AT1B mRNA. These findings suggest that sodium deficiency stimulates
      adrenal AT1A and AT1B receptor mRNA levels primarily via an ANGII-AT1-independent
      mechanism. The preferential increase of adrenal AT1B mRNA during a low-salt
      intake could be explained by the elevation of endogenous ANGII levels during
      sodium deficiency, suggesting that endogenous ANGII acts as an enhancer for
      adrenal AT1B but not for AT1A receptor gene expression via ANGII-AT1 receptors.

PMID- 9644213
TI  - Maitotoxin (MTX) activates a nonselective cation channel in Xenopus laevis
      oocytes.
AB  - Maitotoxin (MTX) may exert its toxic effect by activating ion conductances and
      has been shown to elicit a fertilization-like response in Xenopus laevis oocytes.
      In the present study we investigated the electrophysiological response of stage V
      VI Xenopus oocytes to MTX using the two-microelectrode voltage-clamp technique.
      Membrane voltage (Vm) measurements demonstrated that MTX (50 pM to 1 nM)
      depolarized the oocytes from -49+/-7 to -14+/-1 mV. Subsequent replacement of
      bath Na+ by the impermeant cation NMDG (N-methyl-d-glucamine) shifted Vm from 
      14+/-1 to -53+/-5 mV (n=29). This indicates that MTX activates a cation
      conductance. Indeed, current measurements at a holding potential of -60 or -100
      mV showed that within 10 s of MTX application an inward current component
      developed which was largely abolished by extracellular Na+ removal. After a 1-min
      application of 1 nM MTX the NMDG-sensitive current increased more than 100-fold
      from 0.14+/-0.03 microA to a peak value of 21+/-3 microA (n=11). The effect of
      MTX was concentration dependent with an EC50 of about 250 pM but only slowly
      reversible. Ion substitution experiments indicated that the stimulated
      conductance was nonselective for monovalent cations with a slight preference for
      NH4+ (2.1) > K+ (1.5) > Na+ (1.0) > Li+ (0.7). Regarding divalent cations, a
      complex biphasic response to extracellular Na+ replacement by Ca2+ was observed,
      which suggests that the stimulated channels may have a small Ca2+ permeability
      but that exposure to high extracellular Ca2+ enhances recovery from MTX
      stimulation. No significant conductance for Mn2+ was observed. Application of 1
      mM benzamil, 1 mM amiloride, or 100 microM 1-(beta-[3-(4-Methoxyphenyl)-propoxy]
      4-methoxyphenethyl)-1H-imidazol e hydrochloride (SK&F 96365) reduced the MTX
      stimulated inward current by 81%, 62%, or 65%, respectively. Gd3+ had an
      inhibitory effect of 29% and 38% at concentrations of 10 microM or 100 microM,
      respectively. Flufenamic acid, niflumic acid, (RS)-(3,4-dihydro-6, 7
      dimethoxyisoquinoline-1-gamma1)-2-phenyl-N,N-di-[2-(2,3, 4-trimethoxyphenyl)
      ethyl]-acetamide (LOE908), and 3', 5'-dichlorodiphenylamine-2-carboxylic acid
      (DCDPC), known blockers of other nonselective cation channels, had no significant
      effect. We conclude that MTX activates a nonselective cation conductance in
      Xenopus oocytes. The underlying channels may be involved in changes in Vm that
      occur during the early stages of fertilization.

PMID- 9644214
TI  - Ruthenium red reduces the Ca2+ sensitivity of Ca2+ uptake into cardiac
      sarcoplasmic reticulum.
AB  - Ruthenium red inhibits mitochondrial Ca2+ uptake and is widely used as an
      inhibitor of ryanodine-sensitive Ca2+ channels that function to release Ca2+ from
      the sarcoplasmic reticulum (SR) of muscle cells. It also has effects on other
      Ca2+ channels and ion transporters. To study the effects of ruthenium red on Ca2+
      transport into the SR of cardiac muscle cells, fluorescence measurements of Ca2+
      uptake into cardiac SR vesicles were made. Ruthenium red significantly decreased
      the Ca2+ sensitivity of SR uptake in a dose-dependent manner at concentrations
      ranging from 5 microM to 20 microM. There were no significant effects of
      ruthenium red on the maximum velocity or the Hill coefficient of SR Ca2+ uptake.

PMID- 9644215
TI  - Individual characteristics of human walking mechanics.
AB  - Twenty-four subjects walked at different speeds (V) from 0.4 to 2.6 m s-1, while
      motion and ground reaction forces were recorded in 3-D space. The total
      mechanical energy of each body segment was computed as the sum of the
      gravitational potential, translation and rotation kinetic energies. Energy
      profiles reveal that there are inter-individual differences, particularly at
      moderate and fast V. In some subjects, the energy excursions are less pronounced,
      and tend to evolve out of phase at the lower limbs and trunk. As a consequence,
      there is a better transfer of energy between the trunk and the leg segments,
      resulting in smaller oscillations of the net energy of the whole body. There is a
      threefold variation of the rate of increment of lnPu (the mass-specific mean
      absolute power) with lnV across subjects. We show that this variability cannot be
      simply explained on the basis of the different biomechanical characteristics of
      the subjects, but that it depends on the different kinematic strategies. Subjects
      differ in their ability to minimize energy oscillations of their body segments
      and to transfer mechanical energy between the trunk and the limbs. Individual
      characteristics of the mechanical energy expenditure were correlated with the
      corresponding kinematic characteristics. The changes of the elevation angles of
      the lower limb segments covary along a plane in all subjects. Plane orientation
      (quantified by the direction cosine of the normal with the thigh axis, u3t) at
      any V is not the same in all subjects, but correlates with the net power output:
      smaller values of u3t tend to be associated with smaller values of Pu, and vice
      versa.

PMID- 9644216
TI  - Role of physiological HCO3-buffer on intracellular pH and histamine release in
      rat peritoneal mast cells.
AB  - The purpose of this study was to examine how intracellular pH (pHi) regulation
      and histamine release are affected by HCO3- in rat peritoneal mast cells. The pHi
      was measured using the pH-sensitive dye 2', 7'-bis(2-carboxyethyl)-5(6)
      carboxyfluorescein (BCECF). We observed a pHi of 6.88+/-0.012 (n=24) in resting
      mast cells exposed to a HEPES buffer (pH 7.4), but a sustained drop of 0.21 pH
      units to 6.67+/-0.015 (n=23) when we exposed the mast cells to a HEPES/HCO3-
      buffer equilibrated at all time with 5% CO2 (pH 7.4). This fall in pHi is
      inhibited by the carbonic anhydrase inhibitor dichlorphenamide and is Na+
      independent, indicating the involvement of Na+-independent Cl-/HCO3- exchange
      activity. Furthermore removal of external Cl- in the presence but not in the
      absence of HCO3- reversed the Cl-/HCO3- exchange and induced an alkaline load.
      The recovery from this alkaline load was dependent on external Cl- but
      independent of Na+. Both the alkalinization and the recovery were inhibited by
      the anion transport inhibitor 4, 4'-diisothiocyanatostilbene-2,2'-disulphonic
      acid (DIDS). In addition, 36Cl- uptake measurements confirm the presence of a Cl
      /HCO3- exchanger. Histamine release stimulated by antigen and compound 48/80 was
      substantially reduced in the presence of HEPES/ HCO3- buffer (pHo 7.4, pHi 6.66).
      Histamine release was increased, however, when pHi was clamped to 6.66 in HCO3-
      free media (pHo 6.9). We conclude that: (1) Na+-independent Cl-/HCO3- exchange
      determines steady-state pHi in rat peritoneal mast cells; and (2) the reduction
      in histamine release observed in the presence of HCO3- is not due to its effect
      on pHi per se, but rather on other changes in ion transport.

PMID- 9644217
TI  - The cation selectivity of the sarcoball Ca2+ channel in frog muscle fibres.
AB  - We have measured single-channel currents from sarcoplasmic reticulum (SR) blebs
      (sarcoballs) of frog skeletal muscle fibres using conventional patch-clamp
      electrodes with excised patches. With both the pipette and bath solutions
      containing 50 mM Ca(gluconate)2 the slope conductance of the single channels was
      39.2 pS for the most commonly seen state, with a reversal potential of -0.4 mV.
      The cation selectivity of this channel was investigated by replacing the bathing
      solution with either gluconate or HEPES salts of selected cations. The Goldman
      permeability ratios, calculated from the reversal potentials, were found to be
      P(Ca2+)/P(K+)=2.4, P(Ca2+)/ P(Na+)=2.7, P(Ca2+)/P(Tris+)=3.1, P(Ca2+)/P(Mg2+)=1.0
      and P(Ca2+)/P(Ba2+)=1.1. Each value for the monovalent ions was found to be less
      than the corresponding value reported for the SR ryanodine receptor channel from
      skeletal and cardiac muscle. Single-channel activity could be recorded when the
      preparation was bathed in symmetrical 50 mM Mg(gluconate)2 solutions, and these
      channels had a similar conductance and open probability to that measured when the
      preparation was bathed in symmetrical Ca(gluconate)2 solution. The channel
      activity in symmetrical 50 mM Ca(gluconate)2 solution was insensitive to bath
      applied caffeine (5 mM) and ryanodine (10 microM). The results are in agreement
      with the conclusion that the sarcoball Ca2+ channel is not the ryanodine receptor
      release channel, but possibly a form of the SR Ca2+-ATPase which is uncoupled
      from the catalytic events of the pump and acts as a passive ion channel.

PMID- 9644218
TI  - The rise of nuclear and cytosolic Ca2+ can be uncoupled in HeLa cells.
AB  - It has long been assumed that ionized Ca2+ is transmitted from the cytosol to the
      cell nucleus through the nuclear pore complexes to trigger many nuclear functions
      such as gene transcription after agonist stimulation. However, this hypothesis
      has been challenged recently. In the present study, we have investigated the
      interplay of Ca2+ in the cytosol and nucleus of HeLa cells upon histamine
      stimulation by using confocal microscopy. In resting cells, addition of histamine
      (50 microM) produced synchronous Ca2+ signals in the cytosol and nucleus with a
      stronger fluo-3 emission in the nucleus. Our results also demonstrate that the
      rise of cytosolic and nuclear free Ca2+ can be uncoupled after histamine
      stimulation. This assertion is supported by the following observations: (1) when
      heparin was injected into the cytosol, the increase in fluo-3 fluorescence in the
      cytosol mediated by histamine was almost eliminated while that in the nucleus
      still occurred; (2) when heparin was in the nucleus, the increase in the free
      nucleoplasmic Ca2+ concentration ([Ca2+]n) elicited by histamine was abolished
      while the rise of cytosolic Ca2+ level ([Ca2+]c) was seen; (3) when we injected
      inositol 1,4,5-trisphosphate (IP3) directly into the nucleus, [Ca2+]n increased;
      and (4) in the cells given cytosolic injections of BAPTA-dextran (70 kDa),
      histamine evoked additional Ca2+ transients in the nucleus. These results suggest
      that the nucleus of the HeLa cell has its own IP3-sensitive Ca2+ store and that
      the Ca2+ signals in the nucleus and cytosol can be uncoupled.

PMID- 9644219
TI  - Cellular taurine release triggered by stimulation of the Fas(CD95) receptor in
      Jurkat lymphocytes.
AB  - One of the hallmarks of apoptosis is cell shrinkage which appears to be important
      for cell death. The mechanisms mediating cell volume decrease have, however, not
      been addressed. Mechanisms employed by swollen cells to decrease their cell
      volume include activation of ion transport pathways, such as ion channels and KCl
      cotransport, and release of cellular osmolytes, such as taurine, sorbitol,
      betaine and inositol. The present study has been performed to test for release of
      taurine. To this end Jurkat human T-lymphocytes were loaded with [3H]taurine and
      apoptotic cell death induced by triggering the Fas(CD95) receptor with monoclonal
      crosslinking antibody. Triggering the Fas(CD95) receptor led to a release of 60+/
      5% of cellular taurine within 90 min. The release did not occur prior to 45 min.
      The release coincided with cell shrinkage as evidenced from forward scatter in
      FACS analysis and preceeded DNA fragmentation according to propidium iodide
      staining. The delay of taurine release was not influenced by exchange of medium
      and thus was not due to extracellular accumulation of a stimulator. The Fas(CD95)
      induced taurine release, cell shrinkage and DNA fragmentation were blunted by
      lowering of ambient temperature to 23 degreesC. Following pretreatment of cells
      with Fas(CD95) antibody at 23 degreesC rewarming led to rapid taurine release,
      cell shrinkage and DNA fragmentation, indicating that the temperature-sensitive
      step is distal to the mechanisms accounting for the delay. Osmotic cell swelling
      led to an immediate release of taurine. In conclusion, Fas(CD95) triggering leads
      to delayed taurine release through a temperature-sensitive mechanism.

PMID- 9644220
TI  - Characteristics of L-alanine transport in cardiac sarcolemmal vesicles and into
      isolated cardiac myocytes.
AB  - During cardiac insults, heart cells synthesise and accumulate alanine as a part
      of the anaerobic energy production pathway. The transport of alanine presumably
      influences this pathway, making it important to characterise the L-alanine
      transporter in the heart. In this study, we have investigated the transport of L
      alanine across the sarcolemma using a novel approach, namely utilisation of two
      preparations: cardiac sarcolemmal vesicles and cardiac myocytes. Both
      preparations were isolated from the heart of the same mammalian species. L
      Alanine uptake in both preparations was sodium dependent. In the sarcolemmal
      vesicles, the sodium dependent component was electrogenic and saturated with an
      estimated Michaelis-Menten constant (Km) and maximal reaction velocity (Vmax) of
      0.48+/-0.18 mM and 279.97+/-64.17 pmol/mg per min respectively at room
      temperature. In the isolated myocytes, L-alanine uptake was linear in sodium
      containing media, with an estimated Km and Vmax of 9.65+/-0. 76 mM and 169.81+/
      13.22 pmol/ microl per min respectively at 10 degreesC for the sodium-dependent
      component. Inhibition of cotransport by a variety of substrates indicated that L
      alanine uptake in the heart is mediated by an A- or ASC-like system. These
      characteristics of L-alanine transport suggest that under ischaemic conditions, L
      alanine efflux will be activated, thus allowing for the continuous utilisation of
      other amino acids for energy production.

PMID- 9644221
TI  - Skeletal muscle adaptations to prolonged training, overtraining and detraining in
      horses.
AB  - Thirteen standard-bred horses were trained intensively for 34 weeks and detrained
      for 6 weeks to study skeletal muscle adaptations to prolonged training,
      overtraining and detraining. Training included endurance (phase 1, 7 weeks), high
      intensity (phase 2, 9 weeks) and overload training (OLT) (phase 3, 18 weeks).
      During phase 3, horses were divided into two groups, OLT and control (C), with
      OLT horses performing greater intensities and durations of exercise than C
      horses. Overtraining was evident in OLT horses after week 31 and was defined as a
      significant reduction in treadmill run time in response to a standardised
      exercise test (P<0.05). Relationships between peripheral (skeletal muscle) and
      whole body (maximum O2 uptake, V.O2, max, treadmill run time) adaptations to
      training were determined. Prolonged training resulted in significant adaptations
      in morphological characteristics of skeletal muscle but the adaptations were
      limited and largely completed by 16 weeks of training. Fibre area increased in
      all fibres while the number of capillaries per fibre increased and the
      diffusional index (area per capillary) decreased. Mitochondrial volume density
      continued to increase throughout 34 weeks of training and paralleled increases in
      V.O2,max and treadmill run time. Significant correlations were noted between
      mitochondrial volume and V.O2,max (R=0.71), run time and V.O2,max (R=0.83) and
      mitochondrial volume and run time (R=0.57). We conclude that many of adaptive
      responses of muscle fibre area and capillarity occur in the initial training
      period but that markers of oxidative capacity of muscle indicate progressive
      increases in aerobic capacity with increases in training load. The lack of
      differences between C and OLT groups indicated that there may be an upper limit
      to the ability of training stimulus to evoke skeletal muscle adaptive responses.
      There was no effect of overtraining or detraining on any of the adaptive
      responses measured.

PMID- 9644222
TI  - Replacement of troponin-I in slow-twitch skeletal muscle alters the effects of
      the calcium sensitizer EMD 53998.
AB  - We extracted troponin-I (TnI) from skinned rat and rabbit soleus muscle fibres
      using a modification of the method described by Strauss et al. (FEBS Lett 310:229
      234, 1992) for replacement of TnI in cardiac preparations. Incubation of soleus
      muscle fibres with 10 mmol/l vanadate virtually completely abolished the
      Ca2+dependence of force. Immunoblot analysis revealed that more than 80% of TnI
      had been extracted from the preparations. The Ca2+dependence of force was
      restored by incubation with a complex of cardiac TnI (cTnI) and troponin-C
      (cTnC). We examined the effects of the Ca2+-sensitizing compound EMD 53998 on
      isometric tension in native porcine cardiac and rabbit soleus skinned fibres as
      well as soleus in which the endogenous slow skeletal TnI (ssTnI) had been
      replaced by cTnI (soleus-cTnI). It was found that 10 micromol/l EMD 53998 in
      native soleus increased maximum Ca2+-activated force to 120+/-1.4% of control. In
      soleus-cTnI fibres, maximum force was increased to only 105+/-0.9%, which was
      similar to the effect observed in cardiac muscle (108+/-0.6%). In cardiac muscle,
      10 micromol/l EMD 53998 induced a leftward shift of the pCa-tension relation by
      0.65 log units. In native soleus, DeltapCa was only 0.40. Again, the effect of
      EMD 53998 on soleus-cTnI (DeltapCa=0.56) more closely resembled the response
      found in cardiac muscle than that observed in native soleus muscle. The apparent
      TnI-isoform dependence of the effects elicited by EMD 53998 suggests that its
      actions are modulated by the regulatory proteins of the thin filament.

PMID- 9644223
TI  - 3,5-Diiodo-L-thyronine and 3,5,3'-triiodo-L-thyronine both improve the cold
      tolerance of hypothyroid rats, but possibly via different mechanisms.
AB  - The effects of 3,5-diiodo-L-thyronine (3,5-T2, 2.5-10 microg/100 g BW) on cold
      tolerance, energy expenditure and oxidative capacity of four metabolically very
      active tissues (brown adipose tissue, skeletal muscle, liver and heart) were
      determined in hypothyroid, cold-exposed rats. Hypothyroid rats survived cold for
      only 3-4 days. 3,5-T2 improved survival dose dependently; with 10 microg/100 g BW
      the rats survived 3 weeks (limit of observation). This effect was paralleled by
      an increased energy expenditure of the whole animal for the entire 3 weeks.
      Similar effects were observed in hypothyroid rats treated with 3,3',5-triiodo-L
      thyronine (T3). 3,5-T2 stimulated the specific oxidative capacity (expressed as
      cytochrome oxidase activity per milligram protein) of all four tissues dose
      dependently. When the oxidative capacity was expressed as total activity
      (cytochrome oxidase activity times organ weight), the percentage increases were
      of the same order. T3 exerted similar effects, but the changes in total activity
      were much greater than in specific activity, indicating an effect on the tissue
      trophism. The effect of 3,5-T2 on cold tolerance thus mimics the effect of T3,
      but via different cellular mechanisms. T3 seems to act primarily on the trophism
      of the tissues, while 3,5-T2 may act directly on mitochondria without an effect
      on tissue trophism.

PMID- 9644224
TI  - Hypotonicity stimulates translocation of ICln in neonatal rat cardiac myocytes.
AB  - Cell volume expansion stimulates the efflux of solutes, including the amino acid
      taurine, to accomplish a regulatory volume decrease (RVD). One protein that may
      play a role in taurine efflux is the cytosolic protein ICln. In rat neonatal
      cardiac myocytes under isotonic conditions, ICln is found predominantly (greater
      than 90%) in the cytosol. However, after cell volume expansion by exposure to
      hypotonic medium, ICln rapidly translocates to the particulate fraction (the
      Triton X-114-insoluble fraction). After 2 min in hypotonic medium the percentage
      of ICln in the particulate fraction increases to 30%, 46% at 5 min, 40% at 10
      min, and 25% at 30 min. The time course of this response is similar to that of
      hypotonicity-stimulated taurine efflux. Hypotonicity-stimulated taurine efflux as
      well as ICln translocation parallel the reduction in medium osmolarity. As
      osmolarity decreases, taurine efflux and ICln movement increase. The movement of
      ICln from the particulate back to the cytosolic fraction is accelerated when
      volume-expanded cells are returned to isotonic medium. When ICln is analyzed
      under non-denaturing conditions, a dimer is detected in the particulate fraction
      of volume-expanded cells, along with the monomer. This dimer is not detected in
      the cytosol. Treatment of the particulate fraction from volume-expanded cells
      with the lyotropic agent KSCN caused release of ICln but not Na-K-ATPase into the
      soluble fraction, indicating that translocated ICln associates with membranes in
      the particulate fraction rather than inserting into them.

PMID- 9644225
TI  - Basolateral transport of glutarate in proximal S2 segments of rabbit kidney:
      kinetics of the uptake process and effect of activators of protein kinase A and
      C.
AB  - The kinetics of tubular glutarate uptake, the coupling of glutarate to p
      aminohippurate (PAH) transport and the effect of activators of protein kinase A
      and C on glutarate uptake were studied using isolated S2 segments of proximal
      tubules microdissected from rabbit kidneys without the use of enzymatic agents.
      Because the tubules were not perfused, and hence were collapsed, the tubular
      uptake of [14C]glutarate reflects transport across the basolateral cell membrane.
      To obtain uptake rates most closely related to initial transport rates, 30 s
      glutarate uptake measurements were performed. In a first set of experiments it
      could be shown that preloading proximal S2 segments with glutarate (10(-3 )M)
      stimulated [3H]PAH uptake indicating that glutarate may be a substrate of the PAH
      /dicarboxylate exchanger. The kinetic data revealed a Km value of 0. 62 mM and a
      Vmax value of 84.1 pmol nl-1min-1 for tubular [14C]glutarate uptake across the
      basolateral cell membrane. In contrast to basolateral PAH transport (previous
      studies from this laboratory), tubular 30 s [14C]glutarate uptake was not
      affected by either the phorbol ester phorbol 12-myristate 13-acetate (PMA, 10(-7
      )M), an activator of protein kinase C, or by the membrane-permeant analogues of
      cAMP, dibutyryl cyclic AMP (db-cAMP, 10(-4 )M) and 8-bromoadenosine 3',5'-cyclic
      monophosphate (Br-cAMP, 10(-4 )M). The results indicate that the protein kinases
      A and C have no function in the regulation of the renal basolateral dicarboxylate
      transporter. This finding agrees well with the structural feature of the recently
      cloned rabbit renal dicarboxylate transporter which does not contain any putative
      phosphorylation sites for protein kinase C or cAMP-dependent kinase.

PMID- 9644226
TI  - A hyperpolarization-activated cation current (Ih) contributes to resting membrane
      potential in rat superior cervical sympathetic neurones.
AB  - Using perforated-patch voltage-clamp recording, a prominent hyperpolarization
      activated inward cation current (Ih) has been identified in dissociated, cultured
      and replated, superior cervical sympathetic (SCG) neurones from 17-day-old rats.
      Ih was identified as a slowly activated inward current on hyperpolarizing from 
      60 mV, with an extrapolated null potential (in 3 mM [K+]out) of -42 mV. The
      activation range for Ih was -40 to -100 mV, with a half-activation voltage (V0.5)
      of -63 mV. The current was suppressed by 1 mM Cs+ but not by 1 mM Ba2+. The
      reversal potential for the current change induced by Cs+ agreed with the null
      potential for Ih. Ih conferred strong inward rectification to the current-voltage
      curve negative to -55 mV in both voltage-clamp and current-clamp recording. This
      inward rectification was reduced by 1 mM Cs+. In a sample of eight cells with
      initial resting membrane potentials between -51 and -64 mV, Cs+ increased the
      resting potential of all cells by between 2.5 and 21 mV. These results indicate
      that Ih contributes a tonic inward (depolarizing) component to the maintenance of
      the resting membrane potential in SCG neurones.

PMID- 9644227
TI  - Sarcoplasmic reticulum Ca2+ loading in rabbits 8 and 15 weeks after coronary
      artery ligation.
AB  - Calcium uptake by cardiac sarcoplasmic reticulum (SR) is reported to be reduced
      in heart failure in the human and in a number of animal models. However, the
      majority of studies have examined end-stage heart failure in the human and few
      animal studies have taken account of the duration and severity of left
      ventricular dysfunction. In this study we have compared SR Ca2+ loading in a
      haemodynamically assessed, coronary artery ligation model of heart failure at 8
      and 15 weeks after ligation. Trabeculae were isolated from the right ventricle
      and mounted for isometric tension measurement. They were treated with saponin to
      permeabilize the sarcolemma but retain SR function and bathed in a mock
      intracellular solution including adenosine triphosphate (ATP) and buffered Ca2+.
      Caffeine was used to release Ca2+ from the SR. The amplitude of the caffeine
      induced contracture was used as a quantitative gauge of the Ca2+ content of the
      SR. Eight weeks after ligation, trabeculae demonstrated enhanced SR Ca2+ uptake
      as manifest by larger caffeine-induced contractures (e.g. 200 nM [Ca2+], 120 s
      loading - 38.2+/-9.2 versus 67.3+/-10.1% of maximum Ca2+-activated force, FCa,
      max, P=0.03). At 15 weeks, trabeculae from ligated hearts were not significantly
      different from controls with SR Ca2+ loading returning to control levels (e.g.
      200 nM [Ca2+], 120 s loading - 47.3+/-9.6 versus 30.2+/-12.8% FCa, max, P=0.12).
      These data suggest that SR Ca2+ loading may increase in the early stages of heart
      failure and fall back to normal with an increasing duration of left ventricular
      dysfunction. Increased incidence of spontaneous Ca2+ release observed from the SR
      at 8 weeks and not at 15 weeks may represent an arrhythmogenic mechanism specific
      to the early phase of heart failure.

PMID- 9644228
TI  - Developmental and species differences in the response of the ureter to metabolic
      inhibition.
AB  - The effect of inhibiting oxidative phosphorylation on electrically stimulated
      phasic and high-K+ depolarization-induced tonic contractions in ureteric smooth
      muscle has been investigated. Intracellular [Ca2+] and pH were monitored
      fluorimetrically with simultaneous tension measurement, in adult and neonatal rat
      and guinea-pig ureter. Little difference was found in the response of adult or
      neonatal rat ureters; cyanide abolished phasic contractions and intracellular
      Ca2+ transients. The contractions of the adult guinea-pig ureter were also
      reduced by cyanide, but not as much as those of the adult rat. Neonatal guinea
      pig was, however, remarkably resistant to the effects of cyanide, with force and
      Ca2+ transients remaining at control levels after an initial transient dip. These
      differences between tissues were not apparent when a high K+ concentration was
      used to depolarize tissues and produce maintained [Ca2+]i and force changes;
      cyanide reduced force but not [Ca2+]i in all preparations. Intracellular pH
      decreased in all preparations with inhibition of oxidative phosphorylation, but
      this did not correlate with changes in contraction. It is concluded that there
      are both species and developmental differences in the response to metabolic
      inhibition of the ureter which lead to differing changes in contractile activity.

PMID- 9644229
TI  - The effect of beta-blockade on plasma potassium concentrations and muscle
      excitability following static exercise.
AB  - The effects of beta-blockade on plasma [K+], muscle excitability and force during
      fatiguing exercise were examined. Nine healthy males (mean age 22.3+/-1.7 yr)
      performed a 3-min fatigue protocol that consisted of a sustained submaximal
      contraction (30% of the maximal voluntary contraction, MVC) of the right
      quadriceps muscle. Subjects performed the exercise after treatment with either
      placebo, beta1-selective (metoprolol, 100 mg) or an equipotent dose of non
      selective beta1,2-blockade (propranolol, 80 mg, n=6; 100 mg, n=2; 120 mg, n=1)
      twice daily for 3 days before testing according to a randomized double-blind
      design. Brachial arterial and femoral venous blood samples were drawn before,
      during, and for 15 min following the contraction, together with maximal
      stimulation of the right femoral nerve to evoke a twitch and a compound muscle
      action potential (M-wave); the M-wave amplitude being used as an index of
      sarcolemmal excitability. The exercise-induced rise in plasma [K+] did not differ
      between treatments, but K+ re-uptake during recovery was slower following
      propranolol. The recovery of the twitch was significantly related to the recovery
      of plasma [K+] in all trials, but the evoked M-waves were unaffected by either
      the contraction or the drug treatment. Propranolol resulted in a significantly
      (P<0.05) greater reduction (51.9+/-7.3%) in MVC following the 3-min contraction
      compared with metoprolol (40.7+/-3.6%) or placebo (38. 9+/-3.6%). These results
      suggest that while beta1,2-blockade may significantly affect the recovery of
      muscle force and K+ homeostasis after fatiguing exercise (presumably through an
      inhibition of the Na+,K+-ATPase), it does not appear to affect surface membrane
      excitability.

PMID- 9644230
TI  - Estimation of outward currents in isolated human atrial myocytes using
      inactivation time course analysis.
AB  - The aim was to investigate outward currents in single, isolated, human, atrial
      myocytes and to determine the relative contribution of individual current
      components to the total outward current. Currents were recorded using the whole
      cell patch-clamp technique at 36-37 degreesC. Individual outward current
      components were estimated from recordings of total outward current using a
      mathematical procedure based on the inactivation time course of the respective
      currents. This method allows estimation of outward currents without the use of
      drugs or conditioning voltage-clamp protocols to suppress individual current
      components. A rapidly activating and partially inactivating total outward current
      was recorded when myocytes were voltage clamped at potentials positive to -20 mV
      (peak current density 24. 0+/-0.97 pA/pF at +40 mV; n=107 cells, 33 patients).
      This total outward current comprised three overlapping currents: a rapidly
      inactivating, transient, outward current (Ito1) a slowly and partially
      inactivating current (ultrarapid delayed rectifier, IKur) and a third current
      component which most probably reflects a non selective cation current (not
      characterized). The average current densities at +40 mV were 8.92+/-0.44 pA/pF
      for Ito1 and 15.1+/-0.72 pA/pF for IKur (n=107 cells). Recovery from inactivation
      was bi-exponential for both currents and was faster for Ito1. A slowly activating
      delayed rectifier current (IK) was not found. The current densities of peak Ito1
      and IKur varied strongly between individual myocytes, even in those from the same
      patient. The ratio IKur/Ito1 was 0.5-6.9 with a mean of 1.98+/-0.11 (n=107
      cells), suggesting that IKur is the main repolarizing current. The amplitudes of
      the total outward current, Ito1 and IKur, and the ratio of the latter two were
      independent of patient age (16-87 years).

PMID- 9644231
TI  - Influence of substrate structure on turnover of the organic cation/H+ exchanger
      of the renal luminal membrane.
AB  - We examined the influence of organic cation (OC) structure on the rate of
      turnover of the OC/H+ exchanger in rabbit renal brush-border membrane vesicles
      (BBMV). The rate of efflux of [14C]tetraethylammonium ([14C]TEA) from BBMV,
      measured in the presence of an inwardly directed chemical gradient for test
      agent, provided an indirect measure of activity of the OC/H+(OC) exchanger. The
      trans-stimulation of [14C]TEA efflux from BBMV was a saturable function of
      increasing extravesicular concentration of both unlabeled TEA and
      tetramethylammonium (TMA), with an apparent Michaelis constant (Kt) for the
      interaction of these compounds with the OC/H+(OC) exchanger of 25 microM and 1
      mM, respectively. The effect on [14C]TEA efflux of saturating extravesicular
      concentrations of a series of n-tetraalkylammonium compounds was examined.
      Whereas the short-chain compounds TMA and TEA markedly stimulated [14C]TEA efflux
      (by 830% and 690%, respectively), the long-chain compounds tetrapropylammonium
      and tetrabutylammonium were less effective, increasing efflux by only 40% and
      120%, respectively. When the exchanger was saturated with tetrapentylammonium,
      mediated efflux of [14C]TEA was reduced. Increasing alkyl chain length was also
      correlated with an increase in the inhibitory effect (as measured by the apparent
      inhibition constant, Ki, or the IC50 value) that these compounds had against
      transport of [14C]TEA by the OC/H+(OC) exchanger; i.e., there was a correlation
      between decreasing IC50 and decreasing turnover of the OC/H+(OC) exchanger. This
      same correlation was observed for a broader set of test agents of diverse
      molecular structure, including a series of n-tetraalkylammonium and -phosphonium
      compounds and the OCs, choline, N1-methyl nicotinamide, 1-methyl-4
      phenylpyridinium, and amiloride. Because high affinity of substrates for the
      OC/H+(OC) exchanger is correlated with increasing substrate hydrophobicity, we
      conclude that the interaction of hydrophobic OCs with the renal OC/H+(OC)
      exchanger results in the formation of a substrate-exchanger complex that has a
      comparatively low rate of turnover.

PMID- 9644232
TI  - Endosomes: another extra-mitochondrial location of type-1 porin/voltage-dependent
      anion-selective channels.
AB  - Endocytotic vesicles (EV) isolated from rat renal cortex were subjected to SDS
      polyacrylamide gel electrophoresis and Western blotting. A monoclonal antibody
      against human type-1 porin (31 kDa) detected a strong band of 31 kDa. The same
      antibody has been used as the primary antibody in indirect immunocytochemistry.
      Light microscopy of cryostat sections of rat renal cortex showed a heavy staining
      of EV underneath the brush-border membrane. Electron microscopy was performed by
      "preembedding immunogold staining" of rat renal cortex, the sections of which
      showed an extensive labelling of EV with gold particles. These results
      demonstrate that the expression of type-1 porin is not restricted to outer
      mitochondrial membranes. The biological function of endosomal type-1 porin has as
      yet to be ascertained.

PMID- 9644233
TI  - Transport-mediated release of endogenous glutamate in the vertebrate retina.
AB  - In the present study we measured calcium-dependent, vesicular glutamate release,
      and calcium-independent, transport-mediated glutamate release patterns in the
      vertebrate retina to better understand the sources of elevated glutamate in
      neural tissue under ischemic conditions. A potassium concentration of 40 mM,
      which mimics the extracellular potassium concentration in the central nervous
      system during ischemia, was applied to the bathing medium of a retinal slice
      prepared from zebrafish. High external potassium evoked release of endogenous
      glutamate that was measured using a glutamate-specific fluorometric assay applied
      to the bath. The slice was visualized under 668 nm light using Normarski optics
      and fluorescent images were captured using a cooled charge-coupled device (CCD)
      camera. Following the elevation of external potassium to 40 mM several bands of
      glutamate fluorescence, reflecting the spatial distribution of glutamate release,
      were observed. A calcium-dependent cloud of glutamate was observed in the inner
      plexiform layer, that was antagonized by bath-applied nifedipine. A relatively
      dense glutamate cloud (1-10 microM) was observed over the ganglion cell layer,
      which was blocked by dihydrokainate, a glutamate transport antagonist. In
      contrast, nifedipine, an inhibitor of calcium-dependent neurotransmitter release
      in the retina, failed to block the cloud of released glutamate in the ganglion
      cell layer. These data suggest that under pathological conditions in the eye
      where glutamate levels are elevated surrounding retinal ganglion cells, such as
      observed in some forms of glaucoma, a possible source of the elevated glutamate
      is through a glutamate transporter operating in a reversed direction. A likely
      candidate for mediating this reversed transport of glutamate is the retinal
      Muller cell.

PMID- 9644234
TI  - Single-channel properties of the sarcoplasmic reticulum calcium-release channel
      in slow- and fast-twitch muscles of Rhesus monkeys.
AB  - RyR1 is the main isoform of ryanodine receptor expressed in fast- and slow-twitch
      mammalian skeletal muscles although differences in Ca2+-release kinetics and
      properties have been reported. Single-channel measurements reveal that a large
      proportion (82%) of Ca2+-release channels measured in slow-twitch muscle
      preparations have properties similar to those of the Ca2+-release channels of
      fast-twitch preparations, i.e. the same conductance, an identical sensitivity to
      caffeine and a bell-shaped Ca2+ activation curve for pCa (-log10[Ca2+]) 7 to 3. A
      low proportion (18%) of Ca2+-release channels observed in preparations from slow
      twitch muscles were characterized by a very high activity level. These channels
      were not inhibited at a millimolar concentration of Ca2+. Our data suggest that
      the different properties of Ca2+ release in slow- and fast-twitch muscles might
      not be related to intrinsic properties of the Ca2+-release channels of each type
      of muscle but rather to the co-expression of two isoforms of ryanodine receptor
      and the lower amount of Ca2+-release channels expressed in slow- than in fast
      twitch muscles.

PMID- 9644235
TI  - Real-time measurements of calcium dynamics in neurons developing in situ within
      zebrafish embryos.
AB  - We have developed a non-invasive technique to measure intracellular calcium
      ([Ca2+]i) in neurons growing within intact embryos of the zebrafish (Danio
      rerio). A single blastomere was injected with a calcium-sensitive fluorescent dye
      (Calcium Green dextran) between the 32- and 128-cell stage and the embryo imaged
      between 16 h and 20 h postfertilisation using laser scanning confocal microscopy.
      Labelled nerve cells from embryos preinjected with dye and dissociated at 16 h
      showed a fluorescence increase (66+/-22%; n=11) in response to depolarisation
      with KCl confirming that the dye remained intracellular and was sensitive to
      calcium. In addition, fluorescence changes in activated muscle cells of intact
      embryos showed that the dye was capable of responding to [Ca2+]i changes in vivo.
      Imaging of dye loaded cells over 30-min periods in embryos between 16 and 20 h
      revealed that the majority of neurons within the brain and spinal cord did not
      show spontaneous fluorescence changes distinguishable from noise. However, a
      subset of neurons within the ventral spinal cord exhibited spontaneous,
      repetitive [Ca2+]i oscillations which may have a functional significance during
      neuronal development.

PMID- 9644236
TI  - Suppression of the carbachol-activated nonselective cationic current by antibody
      against alpha subunit of Go protein in guinea-pig gastric myocytes.
AB  - In this study, we investigated which subtype of GTP-binding protein (G protein)
      is related to muscarinic activation of nonselective cation (NSC) channels in
      gastric smooth muscle. Inward cationic current was activated by the application
      of 50 microM carbachol (ICCh) at a holding potential of -60 mV with the same CsCl
      rich solution in both pipette and bath. The same cationic current as ICCh was
      slowly activated by the dialysis of guanosine 5'-O-(3-thiotriphosphate)
      (GTP[gamma-S]) through the pipette. Since it is known that pertussis toxin
      pretreatment can block ICCh, antibodies (Abs) against Galpha,i (anti-Galpha,i) or
      Galpha,o (anti-Galpha,o) were tested. Activation of ICCh was blocked by the
      addition of anti-Galpha,o. However, anti-Galpha,i Abs had no significant effect
      on ICCh. The expression of Galpha,o in guinea-pig gastric smooth muscle was
      confirmed by Western immunoblot analysis. These results suggest that Go-type
      protein may mediate signals from the muscarinic receptor to NSC channel in guinea
      pig gastric myocytes.

PMID- 9644237
TI  - Downstream of phosphatidylinositol-3 kinase, a multifunctional signaling
      molecule, and its regulation in cell responses.
AB  - Phosphatidylinositol (PI)-3 kinase is an enzyme that phosphorylates the D-3
      position of PI and its derivatives. It is activated immediately after growth
      factor or differentiation factor stimulation, suggesting that PI-3 kinase is
      involved in signal transduction of the stimulation. PI-3 kinase appears to play
      various important roles including signaling to the nucleus, vesicle transport,
      and rearrangement of the cytoskeleton since many cell responses which require
      these events are affected by inhibition or activation of PI-3 kinase. To
      understand how PI-3 kinase can act in such multiple ways, it is important to
      identify the factors downstream of PI-3 kinase. In this review, we discuss the
      factors downstream of PI-3 kinase and the methods used to identify them. Recent
      studies revealed that some proteins involved in vesicle transport or in
      rearrangement of the cytoskeleton are regulated by the phospholipids generated by
      PI-3 kinase, implying the mechanism by which PI-3 kinase regulates these cell
      responses.

PMID- 9644238
TI  - Induced mouse models of abnormal sphingolipid metabolism.
AB  - Only a limited number of genetic mouse models of abnormal sphingolipid metabolism
      are known to occur spontaneously. However, recent progress in the combined
      homologous recombination and embryonic stem cell technology allows inactivation
      of any genes of choice once they are cloned. Not only is it possible to generate
      mutant mouse lines that are equivalent to known human genetic disorders but
      genetic conditions unknown or highly unlikely to occur in humans, such as
      simultaneous inactivation of more than one gene, can also be created. Most of the
      human disorders due to genetic defects in sphingolipid catabolism have been
      duplicated in the mouse. With increasing activity in cloning of the enzymes
      involved in sphingolipid biosynthesis, genetic mouse models of abnormal
      sphingolipid biosynthesis are beginning to appear. These models have already
      provided invaluable insight into the metabolism and physiological functions of
      sphingolipids and are expected to be utilized extensively for evaluation of the
      pathogenesis and of treatment approaches of these genetic disorders.

PMID- 9644239
TI  - X-ray structure of a reaction intermediate of L-2-haloacid dehalogenase with L-2
      chloropropionamide.
AB  - The crystal structure of a complex prepared by soaking a single crystal of the
      S175A mutant of L-2-haloacid dehalogenase from Pseudomonas sp. YL in a solution
      containing a poor substrate, L-2-chloropropionamide, has been determined by X-ray
      analysis at 2. 15 A resolution with a crystallographic R factor of 19.8%. The
      present analysis has revealed the structure of the reaction intermediate trapped
      in the crystal. In the intermediate, the substrate moiety lacking chlorine is
      covalently bound to the carboxyl group of D10, and adopts the pro-D-configuration
      at the C2 atom. The amide group of the substrate is hydrogen-bonded with the
      hydroxy group of S118. The methyl group bound to the C2 atom exists in a
      hydrophobic pocket which is important for recognition of the alkyl group of the
      substrate. The guanidino group of R41 has reasonable orientation for halogen
      abstraction.

PMID- 9644240
TI  - The human PTFgamma/SNAP43 gene: structure, chromosomal location, and
      identification of a VNTR in 5'-UTR.
AB  - PTF/SNAPc is a multisubunit complex which specifically recognizes the PSEs of
      small nuclear RNA genes and activates transcription by RNA polymerase II or III.
      Here we describe the isolation and characterization of genomic clones encoding
      the human PTFgamma/SNAP43 gene. The gene spans approximately 29 kilobases, and is
      composed of 9 exons and 8 introns. A major transcription initiation site was
      identified at the position 58 base pairs upstream of the AUG translation
      initiator codon on primer extension analysis with HeLa mRNA. The 5' flanking
      region lacks a typical TATA box but contains many putative binding sites for
      various transcription factors, such as Sp1, Oct1, NF1, AP1, E2F, and USF.
      Immediately downstream of the transcription start site, we found a VNTR of a 17
      bp sequence rich in (G+C). Four different alleles with two to five copies of the
      tandem repeat were identified in 10 individuals examined, indicating a high
      degree of variation at the PTFgamma/SNAP43 locus. In addition, the
      PTFgamma/SNAP43 gene was mapped to human chromosome 14q22 by fluorescence in situ
      hybridization.

PMID- 9644241
TI  - Stable isotope-edited NMR analysis of Ascaris suum mitochondrial tRNAMet having a
      TV-replacement loop.
AB  - Most nematode mitochondrial (mt) tRNAs have a TV-replacement loop (TV loop) which
      replaces the normal T arm and the variable loop in standard tRNAs with a less
      structured loop. The tertiary structure of such tRNAs has been discussed
      theoretically with reference to the crystal structure of yeast tRNAPhe
      [Wolstenholme et al. (1994) Nucleic Acids Res. 22, 4300-4306] and examined
      experimentally by chemical and enzymatic probing [Watanabe et al. (1994) J. Biol.
      Chem. 269, 22902-22906]. The results suggest that most regions of the tRNA other
      than the TV loop are folded in a similar manner to yeast tRNAPhe. To confirm this
      notion more clearly, the tertiary structure of Ascaris suum mt tRNAMet was
      analyzed by NMR using various synthetic tRNAs site-specifically labeled with
      stable isotopes, which were prepared by a combination of chemical synthesis and
      enzymatic ligation. Tertiary interactions involving G(L2), G(L3), U(L4), and U8
      were observed in the NMR spectra of the labeled tRNAs, but those relating to
      G(L5) were not. On the basis of these results, a possible tertiary structural
      model of nematode mitochondrial tRNAMet was constructed.

PMID- 9644242
TI  - Cloning of human polyubiquitin cDNAs and a ubiquitin-binding assay involving its
      in vitro translation product.
AB  - During large-scale in vitro translation analysis of a human full-length cDNA
      bank, we found a clone producing a remarkably smaller translation product than
      that expected from the open reading frame. The cDNA encodes a polyubiquitin, UbC,
      composed of nine tandem repeats of the ubiquitin unit. The bank contained twelve
      UbC cDNAs including four full-length ones. Sequencing analysis of these clones
      showed that UbC cDNAs can be classified into two types, UbC1 and UbC2, in each of
      which there are six polymorphic nucleotide variations. The present UbC cDNA was
      in vitro translated in a rabbit reticulocyte or wheat germ extract to produce a
      free ubiquitin labeled with [35S]methionine. The labeled ubiquitin could be used
      as a substrate for thiol ester formation with ubiquitin-activating enzyme E1 or
      ubiquitin-conjugating enzyme E2.

PMID- 9644243
TI  - Lower mevalonate pyrophosphate decarboxylase activity is caused by the reduced
      amount of enzyme in stroke-prone spontaneously hypertensive rat.
AB  - Spontaneously hypertensive rat (stroke-prone) (SHRSP) has a low serum cholesterol
      level as compared with the normotensive Wistar Kyoto rat (WKY). We previously
      indicated that the lower activity of mevalonate pyrophosphate decarboxylase (MPD)
      was responsible for the reduced cholesterol biosynthesis in the liver of SHRSP
      [Sawamura et al. (1992) J. Biol. Chem. 267, 6051-6055]. To elucidate the
      mechanism of the reduced activity, we purified liver MPD from SHRSP treated with
      cholestyramine and pravastatin in this study. We compared its enzymatic
      properties with those of the enzyme from WKY, and also measured the amounts of
      MPD in the crude extract of various tissues in WKY and SHRSP by Western blot
      analysis. Results indicated that (i) MPD of SHRSP has essentially the same
      properties as MPD of WKY, except for a difference in the dependency on divalent
      cations. (ii) The amount, as well as the activity, of MPD in the crude extract of
      brain and liver was reduced in SHRSP. (iii) There was no difference between SHRSP
      and WKY, in the ratio of the enzyme activity to the amount of MPD in the crude
      extract. These data led us to conclude that the lower activity of MPD was caused
      by the reduced amount of this enzyme in SHRSP.

PMID- 9644244
TI  - Lysyl-tRNA synthetase from Bacillus stearothermophilus. Stopped-flow kinetic
      analysis of enzyme.lysyladenylate formation.
AB  - Amino acid activation reaction of the lysyl-tRNA synthetase [L-lysine:tRNALys
      ligase (AMP forming); EC 6.1.1.6] from Bacillus stearothermophilus was studied
      fluorometrically by the stopped-flow method. The addition of L-lysine to the
      enzyme solution caused quenching of the protein fluorescence and the subsequent
      addition of ATP restored the quenched fluorescence [Takita et al. (1996) J.
      Biochem. 119, 680-689; Takita et al. (1997) 121, 244-250]. In the stopped-flow
      analysis, however, the former fluorescence change (quenching) could not be
      detected, while the latter change (restoration) was detectable. The L-lysine
      binding process was suggested to be much faster than the ATP binding process,
      being completed within the dead-time of the apparatus, ca. 3 ms. The hyperbolic
      dependence of kapp on the initial ATP concentration suggested that the ATP
      binding to the enzyme.L-lysine complex followed a two-step mechanism. Two L
      lysine analogues that exhibit the qualitatively similar behavior to L-lysine in
      the fluorometric titration, L-lysine hydroxamate and L-lysine amide, were
      examined similarly. The two-step process was also suggested for these analogues,
      and the forward rate constant in the rate-determining step for L-lysine amide
      (221+/-7 s-1) was significantly larger than those for L-lysine (45.7+/-4.6 s-1)
      and L-lysine hydroxamate (14. 5+/-1.7 s-1) at pH 8.0, 30 degrees C.

PMID- 9644245
TI  - Characterization of a multi-copper enzyme, nitrous oxide reductase, from
      Rhodobacter sphaeroides f. sp. denitrificans.
AB  - The nitrous oxide reductase from the photodenitrifier, Rhodobacter sphaeroides f.
      sp. denitrificans, has been purified. The enzyme is composed of two identical
      subunits of 66 kDa, and contains four copper atoms per subunit. Copper
      supplementation of the medium resulted in a 3.5-fold increase in the enzyme yield
      with doubly enhanced specific activity. The activity of the purified nitrous
      oxide reductase was completely inhibited by 100 microM zinc ions.

PMID- 9644246
TI  - Molecular cloning, expression, and characterization of a novel mouse liver
      SULT1B1 sulfotransferase.
AB  - A mouse liver homogenate was shown to contain enzymatic activities catalyzing the
      sulfation of 3,4-dihydroxyphenylalanine (Dopa) and tyrosine isomers with a pH
      optimum of 8.25. Western blot analysis revealed a 34 kDa protein exhibiting
      immunologic cross-reactivity to antiserum against rat liver SULT1B1
      sulfotransferase. By employing the reverse transcriptase-polymerase chain
      reaction (RT-PCR) technique, a 910-base pair product encoding the putative mouse
      liver SULT1B1 sulfotransferase was obtained. Using this PCR product as a probe, a
      cDNA containing the entire open reading frame of the mouse liver SULT1B1
      sulfotransferase was cloned from a mouse liver Lambda ZAP cDNA library. The
      nucleotide sequence indicated it is a new enzyme. The deduced amino acid sequence
      exhibited 87.6, 72.3, 55.9, 54.2, 52.8, 51.1, and 49.4% identity to the amino
      acid sequences of the rat liver SULT1B1 sulfotransferase, human thyroid hormone
      sulfotransferase, mouse phenol sulfotransferase, rat liver phenol
      sulfotransferase, rat liver hydroxyarylamine sulfotransferase, mouse estrogen
      sulfotransferase, and rat estrogen sulfotransferase. Upon transfection of COS-7
      cells with an expression vector (pcDNA3) harboring the cDNA encoding this new
      enzyme, a 34 kDa protein exhibiting immunologic cross-reactivity to antiserum
      against the rat liver SULT1B1 sulfotransferase was expressed. The recombinant
      sulfotransferase exhibited enzymatic activities toward Dopa and tyrosine isomers,
      as well as dopamine and 3,3',5-triiodo-L-thyronine. Northern blot analyses
      indicated the SULT1B1 sulfotransferase was predominantly expressed in liver, but
      not in the other ten mouse organs examined. Furthermore, the enzyme was found to
      be expressed in a developmental stage-dependent manner, being at a very low level
      in liver samples from 1-day-old mice and then gradually increasing to the maximum
      level in liver samples from 4-week-old mice.

PMID- 9644247
TI  - Induction of metallothionein isoforms in rat hepatoma cells by various anticancer
      drugs.
AB  - The induction of metallothionein (MT) isoforms (MT-1, -2) by anticancer drugs was
      investigated in cultured rat hepatoma H4 II E C3 cells. The steady-state
      expression of MT-1 mRNAs was higher than that of MT-2 mRNAs. During incubation of
      the cells with various anticancer drugs, namely, adriamycin, epirubicin, cis
      diamminedichloroplatinum(II) (CDDP), and cis-diammine(1, 1
      cyclobutyldicarboxylato)platinum(II), both MT-1 and MT-2 mRNAs were coordinately
      inducible: the levels of isoMT mRNA reached a maxim of approximate by 6-fold at 3
      h. Immunofluorescent studies revealed that the cytosolic fluorescence in the
      cells exposed to 1 microM CDDP for 48 h was more intensified than that in the
      untreated cells. Transfer of antisense oligonucleotides resulted in marked
      reduction of isoMT mRNA, and upon exposure to 5 microM CDDP for 48 h, the
      viabilities of these cells dropped to 25.8% of the controls. These results
      indicate that anticancer drugs are potent inducers of MT isoforms in hepatoma
      cells and that a decrease in cellular MTs enhances the susceptibility of hepatoma
      cells to CDDP. Thus, we conclude that endogenous MTs play a role in determining
      the sensitivity or resistance of cancer cells to clinically important anticancer
      agents.

PMID- 9644248
TI  - Effects of nitration and amination of tyrosyl residues in thermolysin on its
      hydrolytic activity and its remarkable activation by salts.
AB  - Thermolysin is remarkably activated in the presence of high concentrations (1-5
      M) of neutral salts and its activity is enhanced 15 times by 4 M NaCl at pH 7.0
      and 25 degrees C [Inouye, K. (1992) J. Biochem. 112, 335-340]. In this study, the
      effects of nitration and amination of tyrosyl residues in thermolysin on its
      halophilic properties were examined. Nitration and successive amination
      inactivate thermolysin progressively as the degree of modification increases.
      When 16 tyrosyl residues were nitrated, the activity decreased to 10% of that of
      the native enzyme, whereas it recovered to 30% when they were aminated. The
      decrease in the activity by the nitration and amination was shown to be brought
      about only by a decrease in the molecular activity, kcat; the Michaelis constant,
      Km, was unaltered. When 14 tyrosyl residues of thermolysin were nitrated, the
      degree of activation by 4 M NaCl at pH 7.0 decreased from 15 to 10, and this
      decreased further to 5 when the pH of the reaction medium was raised to 8.5.
      However, when the nitrated tyrosyl residues were reduced to aminotyrosyl
      residues, the degree of activation was restored to that of the native enzyme. The
      change in the degree of activation by nitration and amination of thermolysin
      could be due to the change in the ionization of tyrosyl residues, and it was
      suggested that removing negative charges from tyrosyl residues of thermolysin
      enhances its halophilicity.

PMID- 9644249
TI  - Molecular cloning, expression, and site-directed mutagenesis of inorganic
      pyrophosphatase from Thermus thermophilus HB8.
AB  - The genomic DNA encoding the inorganic pyrophosphatase from an extremely
      thermophilic bacterium, Thermus thermophilus HB8 (ATCC27634), was isolated by
      colony hybridization with a probe designed as a part of gene amplified by the PCR
      method, which was derived from the partial amino acid sequence of the enzyme. The
      DNA was cloned into a plasmid vector, pUC118, after digestion with BamHI. The
      inserted nucleotide fragment was about 1.8 kbp in length and the nucleotide
      sequence included a 525 bp open reading frame. The deduced amino acid sequence
      was completely identical with that of the enzyme determined by automated Edman
      analysis of peptide fragments isolated from digests obtained with Staphylococcus
      aureus V8 protease and Achromobacter protease I, and also from products obtained
      on chemical cleavage with cyanogen bromide and 70% formic acid. The subunit of
      this enzyme is composed of 174 amino acid residues with a calculated molecular
      weight of 19,084. Then, the gene was overexpressed in Escherichia coli BL21 (DE3)
      using a plasmid vector, pET15b, system. The recombinant enzyme was fully active,
      and exhibited higher thermostability than the E. coli enzyme. Amino acid residues
      located on the surface of the recombinant enzyme were determined by means of
      limited proteolysis, and the results revealed that the environment of Lys
      residues is almost the same as the crystal structure reported previously
      [Teplyakov, A. et al. (1994) Protein Sci. 3, 1098-1107]. Furthermore, the roles
      of two tryptophan residues were investigated by site-directed mutagenesis, which
      indicated that they may be responsible for the structural integrity and
      thermostability.

PMID- 9644250
TI  - Promoter selectivity of the Bacillus subtilis RNA polymerase sigmaA and sigmaH
      holoenzymes.
AB  - The sigmaH of Bacillus subtilis directs transcription of a large number of early
      sporulation genes, whereas the principal sigma factor, sigmaA, is essential for
      the transcription of the genes for vegetative growth and early sporulation. We
      have purified sigmaA and sigmaH proteins, and characterized their properties. The
      genes encoding sigmaA or sigmaH were separately cloned into an expression vector
      under the control of T7 promoter. Both proteins were overproduced in Escherichia
      coli BL21(DE3) and purified from inclusion bodies after solubilization with
      guanidine hydrochloride. Antigenicities and N-terminal amino acid sequences of
      the overproduced proteins were used to identify both proteins. Unlike sigmaA
      protein, sigmaH protein showed a DNA-binding ability. To compare the promoter
      selectivity of the sigmaA protein with that of the sigmaH protein, transcription
      in vitro of 16 promoters was performed using RNA polymerase holoenzymes
      reconstituted from a purified core enzyme with either sigmaH or sigmaA. These
      holoenzymes correctly recognized each of the cognate promoters; sigmaH-RNA
      polymerase recognized sigmaH promoters but not sigmaA promoters, and vice versa.
      A competition experiment for core RNA polymerase using sigmaA and sigmaH revealed
      that sigmaA had a stronger affinity. We propose that the predicted replacement of
      a sigma subunit in a holoenzyme from sigmaA to sigmaH in vivo at late logarithmic
      growth phase may require an additional factor, or the modification of a core
      enzyme or sigma factor.

PMID- 9644251
TI  - Feedback loops involving Spo0A and AbrB in in vitro transcription of the genes
      involved in the initiation of sporulation in Bacillus subtilis.
AB  - Through mainly in vivo studies, the initiation of sporulation in Bacillus
      subtilis has been shown to depend on the phosphorylation of the Spo0A
      transcription factor mediated by the multicomponent phosphorelay via KinAB (C),
      Spo0F, Spo0B, and Spo0A in this order. RNA polymerase containing sigmaA (EsigmaA)
      or sigmaH (EsigmaH) transcribes the genes of the phosphorelay components.
      Phosphorylated Spo0A is also involved in their expression and is required for the
      induction of sigmaH by repressing its repressor gene abrB. We have examined the
      effects of phosphorylated Spo0A (Spo0A-P) and AbrB on in vitro transcription of
      the genes involved in the Spo0A phosphorylation and initiation of sporulation.
      Spo0A-P repressed EsigmaA-dependent transcription of the kinC and EsigmaH
      dependent transcription of spo0A and kinA. EsigmaH-dependent transcription of
      spo0F was stimulated by Spo0A-P at low concentrations but was repressed by higher
      amounts of Spo0A-P. On the other hand, AbrB repressed EsigmaA-dependent
      transcription of spo0H (sigmaH gene), kinC, and abrB, although its effect was not
      strong. With the present results providing in vitro evidence for the roles of
      Spo0A-P and AbrB as transcriptional regulators, and other results described in
      the literature, the positive and negative feedback loops controlling the temporal
      expression of early sporulation genes are discussed.

PMID- 9644252
TI  - Further characterization of hydrogen peroxide-dependent fatty acid alpha
      hydroxylase from Sphingomonas paucimobilis.
AB  - Although fatty acid alpha-hydroxylase (FAAH) activity has been detected in
      various species, FAAH has not been sufficiently characterized. In this report, we
      describe the properties of FAAH highly purified from Sphingomonas paucimobilis.
      The FAAH was purified by about 5,200-fold. Blotting analysis with a specific
      antibody against the FAAH showed that its apparent molecular mass was
      approximately 43 kDa. FAAH showed alpha-hydroxylation activity in the presence of
      H2O2, but little if any activity with cumene hydroperoxide, t-butyl
      hydroperoxide, or t-butyl peroxybenzonate. The Km value for H2O2 was 72 microM.
      Highly purified FAAH oxidized various non-esterified saturated and unsaturated
      fatty acids including myristic acid, but not myristoyl-CoA. Potassium cyanide and
      sodium azide inhibited the FAAH activity in a concentration-dependent manner.
      Other respiratory chain inhibitors such as rotenone and antimycin A did not
      inhibit the activity. Among cytochrome P450 inhibitors, SKF-525A markedly
      inhibited the activity at the concentration of 2 mM, but CO did not. Imidazole,
      an inhibitor of plant alpha-oxidation, showed no inhibitory effect at 1 mM.

PMID- 9644253
TI  - Characterization of the enzymatic 7-O-acetylation of sialic acids and evidence
      for enzymatic O-acetyl migration from C-7 to C-9 in bovine submandibular gland.
AB  - Microsomes prepared from bovine submandibular glands incubated with radioactive
      AcCoA incorporated acid-insoluble radioactivity, which was dependent on time, and
      the concentrations of AcCoA and proteins, and was inhibited by CoA in a
      concentration-dependent manner. Under the conditions used, the apparent Km for
      AcCoA was 1.63 microM with a Vmax of 21.9 pmol/mg protein.min. The radioactivity
      incorporated was mainly due to the O-acetylation of glycosidically bound Neu5Ac.
      The primary attachment site of O-acetyl groups was exclusively the hydroxyl at C
      7 of Neu5Ac, the presence of an AcCoA:Neu5Ac 7-O-acetyltransferase thus being
      demonstrated. After longer incubation 9-O-acetylated Neu5Ac also appeared,
      suggesting the migration of an ester group from C-7 to C-9. This isomerisation
      was inhibited by heat-inactivation of the microsomal protein, enzymatic
      isomerisation by a "migrase" thus being suggested. Data are presented which lead
      to the assumption that this 7-O-acetylation involves at least two reactions: the
      transport by a translocase of acetyl groups from AcCoA from the cytosol across
      the Golgi membrane, followed by the enzymatic transfer of these acetyl groups
      onto sialic acids in the Golgi lumen.

PMID- 9644254
TI  - Amino-terminal region of SecA is involved in the function of SecG for protein
      translocation into Escherichia coli membrane vesicles.
AB  - Protein translocation across the cytoplasmic membrane of Escherichia coli is
      accomplished by concerted actions of the translocation ATPase SecA and the
      membrane-embedded SecE/Y/G complex. SecA interacts with preproteins and undergoes
      ATP-driven cycles of membrane insertion-deinsertion. To address how SecA
      interacts functionally with other components in the translocation machinery, we
      characterized a SecA mutant lacking amino-terminal 8 amino acid residues (SecA N
      8). Although the absence of the 8 residues did not grossly affect the interaction
      of SecA with a preprotein, ATP, or phospholipids, nor did it affect the intrinsic
      ATPase activity, it gave differential effects on the translocation of different
      preproteins. It also affected the translocation ATPase activity, the ability of
      membrane insertion, and the topology inversion of SecG coupled with the membrane
      insertion-deinsertion of SecA. Most noteworthy, SecA N-8 was pronouncedly
      defective in the translocation of proton motive force-dependent preproteins, in
      which SecG might have a role. We propose that the amino-terminal region of SecA
      is important for the functional interaction with SecG.

PMID- 9644255
TI  - Inhibition of endogenous expression of connective tissue growth factor by its
      antisense oligonucleotide and antisense RNA suppresses proliferation and
      migration of vascular endothelial cells.
AB  - Previously, we cloned an mRNA predominantly expressed in hypertrophic
      chondrocytes by differential display-PCR from a human chondrosarcoma-derived
      chondrocytic cell line (HCS-2/8) that is identical to that of connective tissue
      growth factor (CTGF). In the present study, we investigated the roles of CTGF in
      the proliferation and migration of vascular endothelial cells using its antisense
      oligonucleotide and antisense RNA, because angiogenesis into the hypertrophic
      zone of cartilage occurs at the final step of endochondral ossification.
      Immunohistochemical and immunofluorescence techniques revealed that not only
      hypertrophic chondrocytes but also endothelial cells in the cost-chondral
      junctions of mouse ribs were stained with an anti-CTGF antibody in vivo. Northern
      blot analysis revealed that CTGF was strongly expressed in chondrocytic cells as
      well as bovine aorta endothelial (BAE) cells in culture, but not in other types
      of cells such as osteoblastic cells. Its expression in BAE cells was greater in
      the growing phase than in the confluent phase. When one-half of a monolayer of a
      confluent culture of BAE cells had been peeled off, only the cells proliferating
      and extending into the vacant area were stained with the anti-CTGF antibody. The
      addition of an antisense oligonucleotide inhibited the proliferation and
      extension of the BAE cells into the vacant area. The antisense oligonucleotide
      also inhibited the proliferation of BAE cells in the rapidly proliferating phase.
      In a Boyden chamber assay, pretreatment with the antisense oligonucleotide
      markedly inhibited the migration of BAE cells. Furthermore, the abilities to
      proliferate and migrate of BAE cells, which were stably transfected with
      expression vectors that generate the antisense RNA of CTGF cDNA, were markedly
      lower than those of the control. These findings suggest that endogenous CTGF
      expression is involved in the proliferation and migration of BAE cells.

PMID- 9644256
TI  - Substrate specificities and kinetic properties of proteinase A from the yeast
      Saccharomyces cerevisiae and the development of a novel substrate.
AB  - The substrate specificities and kinetic properties of proteinase A, an
      intracellular aspartic proteinase from the yeast Saccharomyces cerevisiae, were
      determined using a series of synthetic chromogenic peptides with the general
      structure P5-P4-P3-P2-Phe-(NO2)Phe-P2'-P3' [P5, P4, P3, P2, P2', P3' are various
      amino acids; (NO2)Phe is p-nitro-L-phenylalanine]. The nature of the residues
      occupying the NH2-terminal region of the substrate had a strong influence on the
      kinetic constants. Among those tested, Ala-Pro-Ala-Lys-Phe-(NO2)-Phe-Arg-Leu had
      the best kinetic constants (Km = 0.012 mM, kcat = 14.4 s-1, kcat/Km = 1,200 M-1.s
      1). Compared with such aspartic proteinases as pepsin, cathepsin D, and renin,
      the substrate specificity of proteinase A was unique. Based on these results, a
      novel fluorescent substrate, MOCAc-Ala-Pro-Ala-Lys-Phe-Phe-Arg-Leu-Lys(Dnp)-NH2,
      was developed for the sensitive measurement of proteinase A.

PMID- 9644257
TI  - Glycosylation of amphipathic lactoside primers with consequent inhibition of
      endogenous glycosphingolipid synthesis.
AB  - The incubation of amphipathic lactosides with cultured cells was found to prime
      the glycosylation of lactosides whose oligosaccharide structures were exactly the
      same as those of glycosphingolipids produced by cells: B16 melanoma cells
      produced alpha2-3 sialylated lactosides; and PC12 cells, Galalpha1-4- and
      Galalpha1-3Galalpha1-4lactosides. Analysis of the cell-associated glycosylated
      products indicated that C16 series lactoside primers function 5-6 times more
      efficiently as acceptors than C12 series primers. The glycosylated lactosides
      were also secreted into the culture medium. Lactoside primers with longer
      hydrophobic chains hampered the release of glycosylated products from cells. The
      presence of an N-acyl chain in the lipophilic moiety of primers suppressed the
      secretion of glycosylated products. Owing to its overall availability, lactosides
      with the C12 alkyl chain were glycosylated 2-3 times more than C16 series
      lactosides and 1.4 times more than lactosides with the C12 acyl chain. C8
      lactosides did not function as primers under the conditions of this study, but
      they were found to be the best acceptors for sialic acid transfer with the
      soluble enzyme fraction. The incubation of cells with 10 microM N
      hexadecanoylaminoethyl-beta-O-lactoside caused a 30% decrease in endogenous GM3
      of B16 cells and a 34% decrease in Gb3Cer synthesis of PC12 cells. The results of
      the present study demonstrate that lactoside primers serve as an efficient means
      to inhibit endogenous glycosphingolipids in studies to clarify glycosphingolipid
      functions.

PMID- 9644258
TI  - Kinetic characterization of lysine-specific metalloendopeptidases from Grifola
      frondosa and Pleurotus ostreatus fruiting bodies.
AB  - Two zinc-metalloendopeptidases, GFMEP (accession number P81054) and POMEP
      (accession number P81055), from the fruiting bodies of two edible mushrooms,
      Grifola frondosa and Pleurotus ostreatus, respectively, specifically hydrolyze
      peptidyl-lysine bonds (-X-Lys-) in polypeptides. To understand detailed substrate
      specificities and kinetic characters of these enzymes, we have synthesized
      various intramolecularly quenched fluorescent peptide substrates and determined
      their kinetic constants with these substrates. Each synthesized fluorogenic
      peptide has a fluorescent residue, tryptophan, at its carboxyl terminus and a
      quenching group, dinitrophenyl (Dnp), at its amino terminus. Quenching of the Trp
      fluorescence in an intact substrate is relieved on hydrolysis of the -X-Lys-
      bond, giving rise to a continuous increase in fluorescence. The octapeptide
      substrate, Dnp-Ser-Thr-Ala-Thr-Lys-Leu-Ser-Trp, was an efficient substrate for
      both enzymes, the kcat/Km values being 9.8 x 10(6) and 7.0 x 10(5) M-1.s-1 for GF
      and POMEP, respectively. Peptides with aspartic acid adjacent to the Lys residue
      were found to be poor substrates for both enzymes. Neither the shortest peptide,
      Dnp-Thr-Lys-Trp, nor peptides with substitution of L-Arg, L-ornithine, or D-Lys
      for Lys were hydrolyzed by either enzyme. These results confirmed the strict
      specificities of GF- and POMEP toward the peptide bond, -X-Lys-. Substitution of
      Co2+ for Zn2+ enhanced the activity, while the Km values were comparable. All
      peptides not hydrolyzed by either enzyme had inhibitory effects on GFMEP
      activity. The active site structure is discussed in relation to these
      observations.

PMID- 9644259
TI  - Conformation, filament assembly, and activity of single-headed smooth muscle
      myosin.
AB  - Single-headed myosin was prepared by digestion of porcine aorta smooth muscle
      myosin with Staphylococcus aureus V8 protease in the presence of actin. The
      single-headed myosin preparation contained intact light chains, a rod fragment of
      a heavy chain, and a heavy chain of which only a minor fraction contained a nick
      in the head segment. Below 0.2 M NaCl, the single-headed myosin showed a decrease
      in Ca2+-ATPase activity and an increase in the elution time on gel filtration
      HPLC in a phosphorylation-dependent manner, indicating a phosphorylation
      dependent conformational transition between the extended and folded forms. These
      conformations were confirmed by electron microscopic observation of rotary
      shadowed samples of single-headed myosin. However, the conformational transition
      of single-headed myosin occurred in a narrower range with lower salt
      concentrations than that of double-headed myosin. The filament assembly of single
      headed myosin was thus facilitated and phosphorylation-independent. The single
      headed myosin also showed high actin-activated ATPase activity independent of
      phosphorylation. These results indicate that the two-headed structure of smooth
      muscle myosin is not essential for the conformational transition, but is required
      for the phosphorylation-dependent regulation of enzymatic activity and filament
      assembly.

PMID- 9644260
TI  - Functional expression of human golgi CMP-sialic acid transporter in the Golgi
      complex of a transporter-deficient Chinese hamster ovary cell mutant.
AB  - We recently described the cloning of putative human CMP-sialic acid transporter
      (hCST) cDNA [Ishida, N. et al. (1996) J. Biochem. 120, 1074-1078]. The hCST cDNA
      coded for a hydrophobic protein with an amino acid sequence showing a high degree
      of similarity (92% identity) to that of murine CMP-sialic acid transporter. In
      this report, we demonstrate that hCST corrects the CMP-sialic acid transporter
      deficient phenotype of CHO-derived Lec2 cells, as judged from the recovery of WGA
      sensitivity by transformants, and the recovery of CMP-sialic acid transporting
      ability by microsomal vesicles prepared from them. A peptide antibody against the
      C-terminus of the hCST protein detected the cDNA products expressed in the
      microsomes of the transformants. The subcellular localization of the hCST protein
      in the Golgi membrane was demonstrated by immunofluorescence microscopy, using
      the hCST-specific antibody. These results clearly indicate that hCST cDNA encodes
      the human CMP-sialic acid transporter protein. Plasma membrane-selective
      permeabilization combined with immunofluorescence microscopy provided strong
      evidence that the C-terminus of the human CMP-Sia transporter is exposed to the
      cytosol on the outer surface of the Golgi membrane.

PMID- 9644261
TI  - Changes with age of the rat fetuin concentration in serum and its mRNA
      expression.
AB  - Rat fetuin, a counterpart of human alpha2-HS glycoprotein and bovine fetuin,
      shows strong intermolecular binding and association with other serum proteins.
      Therefore, to measure its concentration in rat serum, we pretreated serum samples
      with 1% SDS plus 5% (ca. 0.7 M) 2-mercaptoethanol at 100 degrees C for 3 min, and
      then subjected them to SDS-PAGE under reducing conditions followed by Western
      blotting. We found that the fetuin concentrations in normal rat serum determined
      by Western blotting were 2.5-4.5 mg/ml. These concentrations were three orders of
      magnitude higher than the previously reported concentrations. We also tried to
      measure the fetuin concentration in rat serum by means of an enzyme-linked
      immunosorbent assay after treatment of the samples with 0.1% sodium dodecyl
      sulfate (SDS) plus 10 mM 2-mercaptoethylamine at 100 degrees C for 3 min, but it
      gave a value of about 1/4 of that on Western blotting. Rat fetuin is expressed
      mainly in the liver, with a peak 2-4 weeks after birth, as determined by Northern
      blot analysis. The fetuin mRNA level in the liver changes almost in parallel with
      its serum concentration. The tibia also expresses fetuin, but much less than the
      liver.

PMID- 9644262
TI  - Evidence for chloramphenicol/H+ antiport in Cmr (MdfA) system of Escherichia coli
      and properties of the antiporter.
AB  - We detected chloramphenicol/H+ antiport activity in membrane vesicles of
      Escherichia coli and cloned a gene for the antiporter from chromosomal DNA of E.
      coli. Introduction of the gene into E. coli cells conferred resistance to
      chloramphenicol and ethidium. A slight increase in resistance to acridine orange
      was also observed. Elevated chloramphenicol efflux and ethidium efflux were
      observed in cells harboring a plasmid carrying the gene. Addition of
      chloramphenicol to the assay mixture reduced the efflux of ethidium. Elevated
      chloramphenicol/H+ antiport activity was observed in membrane vesicles prepared
      from cells harboring the plasmid. The pH optimum for the activity was 6.5. We
      sequenced the gene and deduced the amino acid sequence of its product. A sequence
      homology search revealed that it was same as that of Cmr (or MdfA). Thus, it
      became clear that Cmr (MdfA) is the chloramphenicol(and ethidium)/H+ antiporter.

PMID- 9644263
TI  - Antibody against ganglioside GD1c containing NeuGcalpha2-8NeuGc cooperates with
      CD3 and CD4 in rat T cell activation.
AB  - Gangliosides have long been implicated in T cell activation. GD1c with two N
      glycolylneuraminic acids [GD1c(NeuGc,NeuGc)] is the predominant ganglioside in
      rat T cells. In the present study, the anti-GD1c(NeuGc,NeuGc) mAb, AC1, which
      binds to the NeuGcalpha2-8NeuGcalpha2- sequence, was found to enhance Con A
      activated cellular proliferation at a concentration at which AC1 alone did not
      activate the cells. The potentiation by AC1 was observed more consistently and
      effectively in the cellular activation elicited by cross-linking of anti-CD3 and
      anti-CD4, rather than in the cell growth induced by immobilized anti-CD3 alone.
      Moreover, the combination of immobilized anti-CD4 and soluble AC1 had a
      remarkable mitogenic effect. In addition, we have demonstrated the existence of a
      100 kDa protein in rat T cell lysates which reacts with AC1 on Western blots, and
      this interaction is abolished by sialidase-treatment of the membrane. Pronase
      treatment of the T cells, which rendered the 100 kDa protein undetectable on
      Western-blotting, reduced the number of AC1-positive cells by 40-50% on flow
      cytometry. On the other hand, all cells became AC1-negative after sialidase
      treatment. These findings indicated that AC1 reacts with both GD1c(NeuGc,NeuGc)
      and the 100 kDa glycoprotein on rat T cells. Taken together, these results
      predict the presence of a novel regulatory mechanism of T cell activation
      involving CD4 and the NeuGcalpha2-8NeuGcalpha2- sequence.

PMID- 9644264
TI  - Resonance Raman study on reduced flavin in purple intermediate of flavoenzyme:
      use of [4-carbonyl-18O]-enriched flavin.
AB  - 4-Carbonyl-18O]-enriched lumiflavin, riboflavin, and FMN were prepared by
      incubating each corresponding non-labeled flavin in 1 M Na18OH (H218O) at 25
      degrees C. [4-Carbonyl-18O]FAD was prepared from the corresponding riboflavin by
      using FAD synthetase. Isotope effects by [4-carbonyl-18O]-labeling confirmed that
      the 1,709-cm-1 band in the IR spectrum of lumiflavin and the 1,711-cm-1 band in
      the Raman spectrum of FAD are mainly derived from C(4)=O stretching vibrational
      mode. The 1,605-cm-1 Raman band of the anionic reduced flavin in the purple
      intermediate of D-amino acid oxidase (DAO) with D-proline or D-alanine does not
      shift in DAO reconstituted with [4-carbonyl-18O]FAD, although it shifts with
      [4,10a-13C2]- or [4a-13C]FAD. Thus the band is mainly due to the C(4a)=C(10a)
      stretching vibrational mode and includes no contribution from C(4)=O stretching
      vibration. The band frequencies cover a fairly wide range (1,602-1,620 cm-1)
      depending on the enzymes. The frequencies of the reduced flavin in the purple
      intermediates of the dehydrogenases (medium-chain acyl-CoA, short-chain acyl-CoA,
      and isovaleryl-CoA dehydrogenases) are higher than those of the oxidases (DAO and
      L-phenylalanine oxidase). This indicates that the C(4a)=C(10a) bond order of
      reduced flavin in the dehydrogenases with the low reactivity for molecular oxygen
      is stronger than that in the oxidases with high reactivity. Therefore, the band
      frequency of C(4a)=C(10a) stretching may serve as an indicator of the reactivity
      of flavoprotein with molecular oxygen. Furthermore, strong hydrogen bonding of
      flavin at the N(1) moiety with the hydroxyl group of Thr136 in MCAD is probably
      responsible for the strong bond of the C(4a)=C(10a) of reduced flavin in the
      dehydrogenase.

PMID- 9644265
TI  - Involvement of stromal membrane-associated protein (SMAP-1) in erythropoietic
      microenvironment.
AB  - Erythropoiesis is regulated by the hematopoietic microenvironment of the spleen
      and fetal liver in mice. We showed that established stromal cells of these organs
      selectively support erythropoiesis in vitro. To identify the cell surface
      molecule(s) on the stromal cells involved in erythropoiesis, we raised monoclonal
      antibodies against the stromal cells. Using one of these antibodies (11D), we
      cloned a new gene named smap-1 (stroma membrane-associated protein-1). The SMAP-1
      protein deduced from the nucleotide sequence of the cDNA was a newly identified
      membrane protein with direct repeats of the KKD/E units found in MAP1A and MAP1B,
      which is involved in the association with microtubules. By transfection of the
      anti-sense smap-1 cDNA into the stromal cells, we showed that SMAP-1 may have a
      stimulatory effect on stroma-supported erythropoiesis. Its expression was
      detected in the yolk sac, fetal liver, spleen, and bone marrow, and was
      correlated with their erythropoietic activity.

PMID- 9644266
TI  - Adrenocortical and gonadal expression of the mammalian Ftz-F1 gene encoding
      Ad4BP/SF-1 is independent of pituitary control.
AB  - Ad4BP/SF-1 is a transcription factor essential for the development of the adrenal
      gland and the gonads as well as for the maintenance of their functions through
      regulating tissue-specific gene transcription. In the whole body, hypothalamo
      pituitary-gonadal and -adrenal axes are known to play prominent roles in
      mediating the function of the gonads and adrenal. In this study, the effects of
      the tropic peptide hormones secreted by the pituitary on the regulation of the
      rat Ftz-F1 (rFtz-F1) gene encoding Ad4BP/SF-1 were investigated. Immunochemical
      studies revealed that Ad4BP/SF-1 was expressed even in the adrenal cortex of
      hypophysectomized rats. Such persistent expression of Ad4BP/SF-1 was also
      observed in the testes and ovaries of the hypophysectomized animals. In contrast
      to Ad4BP/SF-1, the expressions of steroidogenic P450s were reduced significantly.
      The transcriptional activities of the endogenous and transfected rFtz-F1 genes
      were examined with Y-1 and I-10 cells derived from mouse adrenocortical and
      testicular Leydig cell tumors, respectively. Neither gene appeared to be
      activated significantly by cAMP, whereas both endogenous and exogenous CYP11A
      genes encoding P450(SCC) were activated. Taken together, these observations
      indicate that the expression of the rFtz-F1 gene is mainly regulated by a
      mechanism independent of the neuroendocrine axes.

PMID- 9644267
TI  - Activation of protein phosphatase 2A by the Fe2+/ascorbate system.
AB  - Freshly isolated protein phosphatase 2A (PP2A) was highly active as to the
      dephosphorylation of protein substrates, but lost most of its spontaneous
      activity on prolonged storage, and was converted to a latent form requiring Mn2+
      or Co2+ ions for activity. In this report, we show that the latent form of PP2A
      can be activated by the Fe2+/ascorbate system. Activation of the phosphatase
      required both Fe2+ ions and ascorbate, and the level of activation was dependent
      on the concentrations of both Fe2+ ions and ascorbate. Both the holoenzyme and
      catalytic subunit of phosphatase 2A could be activated by the Fe2+/ascorbate
      system, indicating that direct modulation of the catalytic subunit of the
      phosphatase by the Fe2+/ascorbate system may cause this activation. Several
      common divalent metal ions, including Ca2+, Mg2+, Cu2+, Zn2+, and Ni2+ ions,
      cannot cooperate with ascorbate to activate the phosphatase. Dithiothreitol, a SH
      containing reducing agent, could replace ascorbate in the Fe2+/ascorbate system
      to activate the phosphatase, whereas H2O2, a strong oxidizer, significantly
      diminished the phosphatase activation by the Fe2+/ascorbate system. The results
      indicate that iron ions stabilized in the +2 state by reducing agents can
      activate the phosphatase. Overall, the present study provides initial biochemical
      evidence suggesting that Fe2+ could be a biologically important metal ion
      cofactor responsible for PP2A activation.

PMID- 9644268
TI  - Development of a sensitive and accurate enzyme-linked immunosorbent assay (ELISA)
      system that can replace HPLC analysis for the determination of N1,N12
      diacetylspermine in human urine.
AB  - N1,N12-Diacetylspermine (DiAcSpm)-specific antibodies were raised in rabbits,
      using N-acetylspermine coupled to mercaptosuccinylated BSA via N-(4
      maleimidobutyryloxy)-succinimide as an antigen. Highly DiAcSpm-specific
      antibodies were enriched from crude sera through a series of affinity-based
      fractionations. A competitive ELISA system, intended for measuring DiAcSpm in
      solution, was constructed using this antibody preparation, with N-acetylspermine
      coupled to a synthetic peptide via N-(8-maleimidocapryloxy)-succinimide as a
      solid phase antigen. The Ki value for DiAcSpm with this competitive ELISA system
      was 33 nM, and the cross-reactivity with DiAcSpm, AcSpm, DiAcSpd, N1-AcSpd, and
      N8-AcSpd was 100, 0.29, 0.20, 0.033, and 0.055%, respectively. This procedure can
      be applied to the determination of DiAcSpm in human urine samples, giving highly
      reproducible results. The coefficients of variation obtained were 6.7 and 4.2%
      for within-run and between-run precision, respectively. The correlation
      coefficient between DiAcSpm concentrations in urine estimated by ELISA and those
      by HPLC analysis was calculated to be 0. 99, and the regression equation was
      expressed as y = 1.04x + 0.026 microM.

PMID- 9644269
TI  - Cholesteryl ester transfer protein reaction between plasma lipoproteins.
AB  - The rate of the non-directional transfer of cholesteryl ester and triglyceride by
      human cholesteryl ester transfer protein (CETP) was measured between human plasma
      lipoproteins by monitoring fluorescence spectrum of pyrene-labeled lipid. The
      transfer rates between high density lipoproteins (HDLs) and between low density
      lipoproteins (LDLs) were both directly proportional to the substrate lipid
      concentration within the physiological range of the lipoprotein concentration.
      Higher preference of cholesteryl ester transfer to triglyceride was demonstrated
      with HDL than LDL. Although the highly selective binding of CETP to HDL was
      observed in the electrophoretic analysis, the transfer rate was only moderately
      higher with HDL for cholesteryl ester and not so at all for triglyceride. In
      addition, the rate of cholesteryl ester transfer between LDLs was uninfluenced by
      the presence of a small amount of HDL that is just sufficient to absorb all the
      CETP in the reaction mixture. The results indicated the preferential transfer of
      cholesteryl ester over triglyceride by CETP in the interaction with HDL in non
      directional lipid transfer reaction among lipoproteins. However, the apparent
      binding of CETP to HDL does not seem to play an essential role in this type of
      lipid transfer by CETP.

PMID- 9644271
TI  - Bernstein's papers in motor control 

PMID- 9644270
TI  - Preparation of monoclonal antibodies against N-(gamma
      maleimidobutyryloxy)succinimide (GMBS)-conjugated acetylspermine, and development
      of an enzyme-linked immunosorbent assay (ELISA) for N1,N12-diacetylspermine.
AB  - We have developed three mouse monoclonal antibodies (mAb) of types IgG1 and
      IgG2b, i.e. anti-acetylspermine (Ac-Spm)-1 and 2 (ACSPM-1 and 2), and anti
      acetylspermine (Ac-Spm)-3 (ACSPM-3), respectively, against Ac-Spm conjugated to
      bovine serum albumin via a heterobifunctional cross-linker, N-(gamma
      maleimidobutyryloxy)succinimide (GMBS). Among these mAbs, ACSPM-2 was the most
      useful for the development of an enzyme-linked immunosorbent assay (ELISA) for
      acetylpolyamines (Ac-PAs) with glutaraldehyde (GA)-conjugated N1,N12
      diacetylspermine (2Ac-Spm) or acetylspermine (Ac-Spm) as the solid phase antigen.
      However, GMBS-conjugated Ac-Spm did not behave as a solid phase antigen in the
      competitive ELISA. The ELISA is based on the principle of competition between an
      analyte and the conjugated antigen for the mAb, followed by immunoreaction with
      biotinylated anti-mouse immunoglobulin and horseradish peroxidase-streptavidin.
      The ACSPM-2 mAb reacted with 2Ac-Spm to the highest degree, followed by Ac-Spm,
      N1-acetylspermidine (N1-Ac-Spd), N8,N8-diacetylspermidine (2Ac-Spd), and spermine
      (Spm), the EC50 values being 0.06, 0.25, 7.0, 10, and 60 microM, respectively,
      but exhibited almost no cross-reaction with other polyamine-related compounds or
      amino acids. The method was used to determine the urinary Ac-PA levels in healthy
      subjects, the average value of 0.36 microg of 2Ac-Spm/g creatinine (n = 16) being
      obtained. The ACSPM-2 ELISA for 2Ac-Spm, which was the PA most relevant to the
      analysis of human urine among the five PA analogs mentioned above, might have
      potential for elucidation of the correlation of urinary 2Ac-Spm levels in
      cancers.

PMID- 9644272
TI  - Bernstein's last paper: the immediate tasks of neurophysiology in the light of
      the modern theory of biological activity.

PMID- 9644273
TI  - Rejecting the equilibrium-point hypothesis.
AB  - The lambda version of the equilibrium-point (EP) hypothesis as developed by
      Feldman and colleagues has been widely used and cited with insufficient critical
      understanding. This article offers a small antidote to that lack. First, the
      hypothesis implicitly, unrealistically assumes identical transformations of
      lambda into muscle tension for antagonist muscles. Without that assumption, its
      definitions of command variables R, C, and lambda are incompatible and an EP is
      not defined exclusively by R nor is it unaffected by C. Second, the model assumes
      unrealistic and unphysiological parameters for the damping properties of the
      muscles and reflexes. Finally, the theory lacks rules for two of its three
      command variables. A theory of movement should offer insight into why we make
      movements the way we do and why we activate muscles in particular patterns. The
      EP hypothesis offers no unique ideas that are helpful in addressing either of
      these questions.

PMID- 9644274
TI  - The structure of somatosensory information for human postural control.
AB  - The goal of the present study was to determine the properties of the
      somatosensory stimulus that alter its temporal coupling to body sway. Six
      standing subjects were tested while touching a metal plate positioned either
      directly in front of or lateral to the subject. In each condition, the plate
      moved 4 mm at 0.2 Hz in either the medial-lateral (ML) or anterior-posterior
      direction (AP). The results showed that coupling between body sway and touch
      plate movement was strongest when the touch plate moved in a direction along the
      longitudinal axis of the arm. Coupling strength was weaker when the touch plate
      moved perpendicular to the longitudinal axis of the arm. The results consistently
      show that a radial expansion stimulus was more effective than a lamellar-type
      stimulus at the fingertip. Moreover, somatosensory information from a surface is
      interpreted in terms of the orientation of the contact limb and the potential
      degrees of freedom available through its movement.

PMID- 9644276
TI  - The control of sequential goal-directed movement: learning to use feedback or
      central planning?
AB  - Fifteen participants practiced a two-target sequential aiming movement with
      either full vision of the movement environment, vision during flight, or vision
      while in contact with the first target. After 100 acquisition trials,
      participants performed a retention test in their own condition and then were
      transferred to each of the other two vision conditions. Both performance and
      kinematic data indicated that rather than becoming less dependent on visual
      information with practice, subjects learned to adjust their movement trajectories
      to use the visual information available in their particular vision condition.
      Although transfer to a degraded vision condition disrupted performance, when
      vision was augmented participants quickly adjusted their aiming trajectories to
      use the added information. The findings suggest that at least part of learning
      involves the development of rapid and efficient procedures for processing
      afferent information, including visual response-produced feedback.

PMID- 9644275
TI  - Stability of rhythmic finger movement in children with a developmental
      coordination disorder.
AB  - The stability of single and bimanual (i.e., in-phase and antiphase) rhythmic
      finger movements was studied in 24 children with a developmental coordination
      disorder (DCD) and 24 matched controls from a dynamic pattern perspective.
      Stability was assessed by applying perturbations and measuring the time the
      system needed to return to its initial stability (i.e., the relaxation time). In
      addition, fluctuations of the patterns were measured. For antiphase coordination
      patterns, the frequency at which loss of stability occurred was also determined.
      Children with DCD displayed less stable single and bimanual rhythmic coordination
      patterns than control children. Further, within the DCD group, 9 children were
      identified as having particularly poor bimanual coordination stability.
      Individual differences suggested that variability of individual limb oscillations
      might have contributed to this poorer interlimb coordination stability. Findings
      were discussed in relation to a previous study on DCD in which the Wing
      Kristofferson timekeeper model was applied.

PMID- 9644277
TI  - Considering handedness in studies involving manual control.
AB  - With studies of motor behavior that feature manual control, it is suggested that
      the methodology used to select subjects in reference to handedness be reviewed.
      This suggestion is in view of the recommendation that simply asking subjects to
      identify their writing hand is inadequate to define handedness. Complementing
      this are recent findings in neuroscience indicating differences, at times
      significant, in information-processing behavior based on handedness
      classification. A brief review of recently published studies in two prominent
      outlets for motor behavior research confirms that most reports provide minimal
      (and sometimes no) information regarding handedness and the method used for
      assessment. Recommendations for addressing the problem include using an
      acceptable preference inventory, selecting only those subjects with strong
      lateral characteristics, and briefly describing the methodology used for the
      reviewing audience.

PMID- 9644278
TI  - Bernstein's rejection of Braune and fischer: studies on the physiology and
      pathology of movements (1936).

PMID- 9644280
TI  - Introduction to a special selection of research papers 

PMID- 9644279
TI  - Is dynamical systems modeling just curve fitting?
AB  - The development of mathematical tools for describing dynamical systems has made
      it possible to characterize forms of behavior that could not be characterized
      before. This represents progress, but the enterprise runs the risk of being
      nothing more than curve fitting if investigators fail to identify the physical,
      biological, or psychological mechanisms which are common to systems that follow
      the same dynamical regime and which are not common to systems that do not follow
      the same dynamical regime.

PMID- 9644281
TI  - Bimanual circle drawing during secondary task loading.
AB  - Seven right-handed participants performed bimanual circling movements in either a
      symmetrical or an asymmetrical coordination mode. Movements were paced with an
      auditory metronome at predetermined frequencies corresponding to transition
      frequency, where asymmetrical patterns became unstable, or at two-thirds
      transition frequency where both symmetrical and asymmetrical patterns were
      stable. The pacing tones were presented in either a high (1000 Hz) or low (500
      Hz) pitch, and the percentage of high-pitched tones during a 20 s trial varied
      between 0% and 70%. Participants were instructed to count the number of high
      pitched pacing tones that occurred during a trial of bimanual circling. Overall,
      the symmetrical pattern was more stable than the asymmetrical pattern at both
      frequencies. Errors on the tone-counting task were significantly higher during
      asymmetrical circling than symmetrical circling but only at the transition
      movement frequency. The results suggest that cognitive processes play a role in
      maintaining coordination patterns within regions of instability.

PMID- 9644282
TI  - Fractioned reflex and reaction time in children with developmental coordination
      disorder.
AB  - The patellar tendon reflex (PTR) and simple visual reaction time (RT) were
      fractionated and compared in 40 subjects with developmental coordination disorder
      (DCD) and normal coordination (NC) in two age groups. Four equal groups of
      subjects, 6 years DCD (6DCD), 6 years NC (6NC), 9 years DCD (9DCD), and 9 years
      NC (9NC) were compared using ANOVA for the main effects of coordination and age.
      PTR and its components of reflex latency and motor time were not significantly
      affected by the level of coordination; however, a significant coordination by age
      interaction (p < .05) revealed an increased motor time in the 6DCD group. RT,
      premotor time, and motor time were all significantly (p < .05) increased in
      children with DCD; the increased RT and premotor time support earlier findings,
      whereas the increased motor time has not previously been found. These findings
      suggest that the processing of reflexive and volitional responses by children
      with DCD differs from that of their NC peers.

PMID- 9644283
TI  - Provision of external cues and movement sequencing in Parkinson's disease.
AB  - The basal ganglia (BG) may play a part in motor sequencing. Individuals with
      Parkinson's disease (PD) may exhibit progressive slowing (sequence effect) during
      motor sequences such as writing (micrographia) and gait. In the present study, a
      serial two-way choice reaction time (CRT) task was employed, in which advance
      information about each next movement was not provided until the participant began
      moving, thereby assessing the participant's ability to utilize advance
      information. Participants were 13 individuals with idiopathic PD and 13 age
      matched controls. Both PD subjects and controls showed a significant sequence
      effect in the absence of advance information, possibly reflecting difficulty in
      initiating and maintaining movement without external cues. PD subjects and
      controls both exhibited a sequence effect at moderate levels of advance
      information. At high levels of advance information, PD subjects showed the effect
      but controls did not, suggesting that controls, unlike PD subjects, were able to
      use the extra information to facilitate performance, perhaps reflecting more
      frontal aspects of impairment in PD.

PMID- 9644284
TI  - Foreperiod length, but not memory, affects human reaction time in a precued,
      delayed response.
AB  - The effect of foreperiod length on reaction time in memorized (MM) and
      nonmemorized (NM), precued, delayed responses was investigated. Six subjects
      participated in one long and one short foreperiod schedule testing session. An
      aiming task, using elbow supination/pronation, in response to a visual stimulus
      was employed. In the MM condition, target spatial information was available for a
      fraction of the foreperiod duration. In the NM condition, target information was
      available continuously until the subject attained the target position. Subjects
      responded with a significantly longer latency in the long foreperiod schedule.
      Within each foreperiod schedule, the shortest foreperiod resulted in
      significantly longer reaction time. However, the absolute value of foreperiod did
      not have a major effect on reaction time latency. Memorization and
      nonmemorization conditions did not affect reaction time.

PMID- 9644285
TI  - Does having to remember the position of a target improve reaction time?
AB  - In the monkey, reaction time in a precued delayed response task was found to be
      faster when the animals had to remember the precue than when it was continually
      available (Smyrnis, Taira, Ashe, & Georgopoulos, 1992). We investigated whether
      this reflects a general principle that applies to all types of precued tasks.
      However, we found the opposite result in a simpler task in humans. Our findings
      suggest that the beneficial effect of a memory requirement on reaction time in
      the monkey may reflect an effect of task difficulty, rather than a fundamental
      process involved in all precued movement tasks.

PMID- 9644286
TI  - Lip and tongue function in multiple sclerosis: A physiological analysis.
AB  - A physiological analysis of the articulatory function of 16 adults with multiple
      sclerosis (MS) was performed using lip and tongue transduction systems. Sixteen
      nonneurologically impaired adults, matched for age, gender, and education, served
      as controls. The MS speakers demonstrated patterns of tongue function that were
      significantly different from those of the control speakers. Specifically, the MS
      speakers were found to have significantly reduced tongue strength, endurance, and
      rate of repetitive movements. In addition, preclinical signs of lingual
      dysfunction were evident in nondysarthric MS speakers on endurance and rate tasks
      when compared to control subjects. These physiological findings could account for
      the perceptual findings of impaired articulation and reduced intelligibility. No
      lip dysfunction was found on either the physiological or perceptual assessments.

PMID- 9644287
TI  - Effect of oral levodopa treatment on articulatory function in Parkinson's
      disease: preliminary results.
AB  - To quantify lip function in 16 patients with Parkinson's disease, a computerized
      semiconductor lip pressure transducer system was used prior to subjects being
      administered oral levodopa and at approximately 0.5 hr, 1.5 hr, and 3.0 hr
      postmedication. Two blood samples were taken from each subject at varying times
      during the levodopa dosage interval, and the exact time and dosage of levodopa
      were noted. Lip function measurements were expressed as percentage changes from
      baseline and were plotted for each subject against time and levodopa
      concentrations to determine the effects of levodopa therapy on articulatory
      function. The results supported the effectiveness of levodopa therapy in
      improving lip function. In particular, lip pressures recorded during both speech
      and nonspeech tasks tended to improve after levodopa administration, the lip
      measures improving somewhat in parallel with the rise and fall of blood plasma
      levodopa concentrations. Evidence of a hysteresis effect was noted.

PMID- 9644288
TI  - Bernstein's revolution in movement medicine: coordination disorders and the
      recovery of walking biodynamics after cerebrovascular injuries (1954).

PMID- 9644289
TI  - Recent tests of the equilibrium-point hypothesis (lambda model).
AB  - The lambda model of the equilibrium-point hypothesis (Feldman & Levin, 1995) is
      an approach to motor control which, like physics, is based on a logical system
      coordinating empirical data. The model has gone through an interesting period. On
      one hand, several nontrivial predictions of the model have been successfully
      verified in recent studies. In addition, the explanatory and predictive capacity
      of the model has been enhanced by its extension to multimuscle and multijoint
      systems. On the other hand, claims have recently appeared suggesting that the
      model should be abandoned. The present paper focuses on these claims and
      concludes that they are unfounded. Much of the experimental data that have been
      used to reject the model are actually consistent with it.

PMID- 9644290
TI  - Intrinsic muscle properties facilitate locomotor control - a computer simulation
      study.
AB  - The purpose of this study was to investigate, theoretically, to what extent
      muscle properties could contribute to recovery from perturbations during
      locomotion. Four models with different actuator properties were created: the FLVT
      model, which encompassed force-length (FL) and force-velocity (FV)
      characteristics of human muscles as well as muscle stimulation inputs as
      functions of time (T); the FLT model, which had muscles without force-velocity
      characteristics; the FVT model, which had muscles without specific force-length
      characteristics; and the MT model, which had no muscles but was driven by joint
      moments (M) as a function of time. Each model was exposed to static and dynamic
      perturbations and its response was examined. FLVT showed good resistance to both
      static can dynamic perturbations. FLT was resistant to static perturbation but
      could not counteract dynamic perturbation, whereas the opposite was found for
      FVT. MT could not counteract either of the perturbations. Based on the results of
      the simulations, skeletal muscle force-length-velocity properties, although
      interactively complex, contribute substantially to the dynamic stability of the
      musculoskeletal system.

PMID- 9644291
TI  - Learning transfer from flexion to extension movements: importance of the final
      position.
AB  - Nine subjects (experimental group) were tested on rapid elbow flexion and
      extension movements performed in the same final position, prior to and after
      extensive practice of the movements. Nine additional subjects (control group)
      were also tested, but without any practice between the tests. Comparison of the
      pretest and posttest results suggested that the experimental group decreased
      their variable error (i.e., standard deviation of the final movement position) in
      both practiced (elbow flexion) and nonpracticed (elbow extension) movement. The
      control group, however, did not improve in either of tested movements. The
      experimental group demonstrated lower variable error in the nonpracticed elbow
      extensions than the control group, while the same difference for practiced elbow
      flexion movements was slightly below the significant level. The results support
      the importance of the final position in programming of rapid, self-terminated
      movements; however, they do not rule out the role of other kinetic and kinematic
      variables (such as movement distance).

PMID- 9644292
TI  - Relative coordination reconsidered: a stochastic account.
AB  - Von Holst (1939/1973) parsed intersegmental coordination into relative and
      absolute to distinguish moderate and extreme forms. Kelso and DeGuzman (1992)
      discussed an interpretation of relative coordination in terms of the chaotic
      phenomenon of intermittency. The data of concern (DeGuzman &amp Kelso, 1991) do
      not, however, exclude a stochastic interpretation, which is detailed here
      following earlier suggestions. The key difference is modeling relative
      coordination by stochastic variability about weak attractors rather than by
      deterministic variability about remnants of attractors ("ghost attractors"). The
      intermittency interpretation is not robust in the presence of noise and,
      therefore, is not well disposed to account for uncertainty in detailing a model
      of behavioral data or its parameters. In contrast, the stochastic interpretation
      is based upon an approximation of unknown underlying processes in the form of
      Gaussian white noise. A stochastic method for estimating model parameters from a
      stationary probability distribution and a mean first passage time is illustrated
      using experimental and simulated data.

PMID- 9644293
TI  - Facilitation of a hand muscle response to stimulation of the motor cortex
      preceding a simple reaction task.
AB  - Transcranial magnetic stimulation (TMS) of the motor cortex was used to produce
      compound motor evoked potentials (cMEPs) in the first dorsal interosseus (FDI)
      muscle. The size of cMEPs was measured as an index of corticospinal excitability
      before and after initiation of a simple reaction task (SRT). The SRT, consisting
      of an abduction of the right index finger against a vertical support in response
      to a 1 kHz cueing tone, was performed in 6 healthy male subjects. cMEPs were
      facilitated when timed to occur just before the fastest simple reaction time
      (fSRT). When the cMEP was placed 15.5 +/- 1.5 ms before the fSRT, its amplitude
      increased to 176 +/- 36% of the control response seen in the relaxed state (no
      SRTs). Facilitation of the cMEP increased to 382 +/- 43% of the control when it
      was placed 11.9 +/- 1.5 ms after the fSRT. The facilitation of cMEP responses
      prior to the SRT is discussed with particular reference to the premovement
      potential that may be recorded over the cortex prior to a voluntary movement.

PMID- 9644294
TI  - Pointing to remembered targets in 3-D space in Parkinson's disease.
AB  - A three-dimensional tracking system was used to examine whether subjects with
      Parkinson's disease (PD) would show characteristic performance deficits in an
      unconstrained pointing task. Five targets were presented in a pyramidal array in
      space to 11 individuals with mild to moderate PD and 8 age-matched controls.
      After the target was indicated, subjects closed their eyes and pointed to the
      remembered target locations without vision. Despite the absence of visual
      feedback during movement, PD subjects were as accurate overall as controls.
      However, PD subjects showed greater variable errors, more irregular trajectories,
      and a vertical endpoint bias in which their endpoints were significantly lower
      than controls. They also showed deficiencies in the compensatory organization of
      joint rotations to ensure consistency in azimuthal (horizontal) positioning of
      the arm endpoint. We concluded that, under appropriate task conditions, PD
      subjects may not show overall deficits in accuracy even when making targeting
      movements at normal speed without visual feedback. Nevertheless, our findings
      indicate that there are certain dimensions of performance which are selectively
      altered in Parkinson's disease even when overall performance is normal.

PMID- 9644295
TI  - Rare alteration of genomic structure or expression of the DPC4 gene in
      myelogenous leukemias.
AB  - We examined homozygous deletion, point mutation and expression of DPC4 gene, a
      recently isolated candidate pancreatic tumor suppressor gene, in 53 patients with
      myelogenous leukemias and 5 cell lines. The patients consisted of 34 cases of
      chronic myelogenous leukemia including 22 in the chronic phase, 3 in the
      accelerated phase, and 9 in blastic crisis, and 19 with acute myelogenous
      leukemia including 9 at the initial presentation and 10 at relapse. Polymerase
      chain reaction (PCR)-based deletion analysis for DPC4 exon 8 and PCR-single
      strand conformation polymorphism study for the entire coding region were carried
      out. Homozygous deletion or subtle mutation was not detected in any of the
      samples examined. However, 3 patients with various clinical phases showed a
      decrease of DPC4 expression. These results suggest that DPC4 alteration is not a
      crucial event in the development or the progression of myelogenous leukemias.

PMID- 9644296
TI  - Pentoxifylline synergizes with all-trans retinoic acid to induce differentiation
      of HL-60 myelocytic cells, but suppresses tRA-augmented clonal growth of normal
      CFU-GM.
AB  - All-trans retinoic acid (tRA) has been shown to promote terminal differentiation
      of promyelocytic leukemia cells, but frequently induce hyperleukocytosis and
      pulmonary leakage syndrome. Employing pentoxifylline (PTX), a phosphodiesterase
      inhibitor which could raise intracellular cAMP and modulate leukocyte activation,
      we sought to investigate if PTX could enhance tRA-induced promyelocytic leukemic
      cell differentiation but suppress tRA-augmented growth and activation of human
      granulocytes. tRA could significantly suppress clonal growth of U937 and HL-60
      leukemic cells but enhanced the CFU-GM formation of normal bone marrow cells (22
      +/- 6 vs. 90 +/- 16 CFU/well). PTX significantly augmented tRA suppression of
      clonal growth of U937 and HL-60 leukemic cells but suppressed tRA-augmented CFU
      GM formation of normal bone marrow cells (90 +/- 16 vs. 25 +/- 9 CFU/well). In
      addition, PTX enhanced tRA-induced growth inhibition and differentiation of
      promyelocytic HL-60 leukemic cells, but suppressed respiratory burst activation
      by the immature granulocytic HL-60 cells and suppressed CD11b adhesion molecule
      expression by mature granulocytes. PTX similar to dibutyric cAMP promoted HL-60
      myelocytic leukemic cell differentiation and growth inhibition, whereas PTX, in
      contrast to dibutyric cAMP which could augment phorbol myristate acetate (PMA)
      elicited respiratory burst activity by immature granulocytes, suppressed the PMA
      elicited respiratory burst activity by immature and mature granulocytes. PTX did
      not raise the intracellular cAMP level of HL-60 cells, but partly suppressed the
      dibutyric cAMP-elicited elevation of intracellular cAMP level. Results from these
      studies suggest that PTX might act through different signaling pathways to
      enhance tRA-induced myelocytic leukemic cell differentiation but prevent from
      hyperreactive normal granulopoiesis and granulocyte activation.

PMID- 9644297
TI  - Haematological effects of oral cobalamin preparations on patients with
      megaloblastic anaemia.
AB  - We investigated the haematological effects of a massive dose of oral cobalamin
      (vitamin B12) on patients with cobalamin deficiency anaemia who had severe
      anaemia with a few neurological impairments and found that oral treatment was
      almost as effective as conventional injection therapy. The recovery of
      haematological indices with oral cobalamin preparations was slightly slower than
      with parenteral preparations, although the subjective symptoms disappeared soon
      after the start of therapy. The results of this study indicate that oral
      treatment keeps the cobalamin body stores satisfactorily filled and might be
      useful for older patients in whom injecting might be difficult.

PMID- 9644298
TI  - Effect of discontinuing prophylaxis with norfloxacin in patients with hematologic
      malignancies and severe neutropenia. A matched case-control study of the effect
      on infectious morbidity.
AB  - The use of fluorinated quinolones for prophylaxis of infections in neutropenic
      cancer patients has led to a reduction of infections with gram-negative enteric
      bacilli, but there is concern about the emergence of antibiotic-resistant entero
      bacterial infections and a rise of gram-positive bacteremias. Due to these
      concerns, in mid-1995 the use of prophylactic norfloxacin was discontinued in our
      unit. In order to evaluate the impact of this measure on the infectious morbidity
      in our unit, 91 severe neutropenic episodes in 58 patients with hematologic
      malignancies who did not receive norfloxacin prophylaxis (NO group) were closely
      matched to 91 episodes in 60 patients who received norfloxacin prophylaxis
      (NORFLO group). There were no differences in the incidence of febrile
      neutropenia, fever of unknown origin or bacteremia during the first febrile
      episode. There was a trend for a higher rate of coagulase-negative staphylococcal
      bacteremia in the NORFLO group (5 vs. 11 cases in the NO and NORFLO groups,
      respectively, p = NS). Enterobacterial bloodstream infections were more frequent
      in the NO group (13 vs. 2 cases, respectively, p = 0.01), especially Escherichia
      coli (9 vs. 1 case, respectively, p = 0.01). Twelve of 13 enterobacterial
      isolates in the NO group were sensitive to the fluoroquinolones vs. 0/2 in the
      NORFLO group (p = 0.07). We conclude that the abrupt discontinuation of
      norfloxacin prophylaxis in our ward led to a rapid increase in the rate of
      fluoroquinolone-susceptible enterobacterial infections, with a scarce impact on
      infectious morbidity. This suggests that the selection of resistant flora in an
      inpatient ward by prophylactic antimicrobials may be reversible following the
      discontinuation of the prophylactic agent(s).

PMID- 9644299
TI  - Serum hyaluronan as a marker of liver fibrosis in hemophiliacs with hepatitis C
      virus-associated chronic liver disease.
AB  - We measured serum type III procollagen peptide, type IV collagen (IV-C), and
      hyaluronan (HA) in 36 hemophiliacs with hepatitis C virus (HCV)-related chronic
      liver disease. We also measured these markers in 19 interferon (IFN)-treated
      patients before and after a 6-month course of IFN-alpha. The serum concentrations
      of IV-C and HA were correlated with the stage of fibrosis (IV-C r = 0.38; HA r =
      0.78). These markers fell only in complete responders showing sustained clearance
      of serum HCV RNA by IFN. These results suggest that, in hemophiliacs with chronic
      liver disease, serum HA measurement might be an alternative to liver biopsy and
      reflect the response to IFN.

PMID- 9644300
TI  - Autoimmune thrombocytopenia associated with hepatitis C virus infection.
AB  - We have retrospectively analyzed a series of 19 patients with hepatitis C virus
      (HCV) infection and chronic thrombocytopenia not attributable to hypersplenism or
      to other causes. Antiplatelet antibodies were present in 81% of cases. Response
      to prednisone was observed in 6 of 7 patients and 1 of 3 patients responded to
      intravenous immunoglobulins. No case of reactivation of liver disease was
      observed during or after therapy. We consider that the possibility of an
      underlying mechanism should be evaluated in thrombocytopenic patients with HCV
      infection who do not present hypersplenism. These patients could benefit from
      steroid treatment.

PMID- 9644301
TI  - Coexistence of chronic myelogenous leukemia and multiple myeloma. Case report and
      review of the literature.
AB  - A case report of simultaneous presentation of chronic myelogenous leukemia (CML)
      and multiple myeloma (MM) in a 72-year-old female is described. Our case was
      typical of Ph1-positive and chimeric bcr-abl messenger RNA-positive CML.
      Furthermore, a marked IgG (kappa-type) paraproteinemia was present. Fluorescence
      in situ hybridization showed that 97% of marrow nucleated cells were positive for
      bcr-abl fusion signal, when myeloma cells in the bone marrow amounted to 19.0%.
      In the literature survey, 4 similar cases with coexistence of CML and MM have
      been identified.

PMID- 9644302
TI  - Remission induction by granulocyte colony-stimulating factor in hypoplastic acute
      myelogenous leukemia complicated by infection. A case report and review of the
      literature.
AB  - A patient with hypoplastic acute myelogenous leukemia (AML) who achieved
      remission with granulocyte colony-stimulating factor (G-CSF) alone is reported.
      The 59-year-old male patient received antibiotics and G-CSF but not any
      antileukemic drugs because of ongoing pneumonia. After 2-week administration of G
      CSF, he achieved complete remission and his pneumonia improved. Since leukemia
      relapsed after 3 months, he received G-CSF again for 5 weeks, but failed to be in
      remission this time. He underwent antileukemic chemotherapy and achieved second
      remission. When he suffered from a second relapse after 7 months, intensive
      chemotherapy was commenced but was stopped on the 2nd day since his general
      condition became very poor due to septicemia. He began to receive G-CSF again and
      achieved third complete remission after 3 weeks. In vitro studies showed that G
      CSF did not stimulate proliferation of the patient's blast cells although they
      expressed G-CSF receptor on their surface. Moreover, G-CSF induced
      differentiation of the blast cells into segmented neutrophils in vitro. According
      to the literature, in all of the 12 patients with AML who were reported to
      achieve remission by G-CSF the course was complicated by infection, and 7 of the
      patients were diagnosed as hypoplastic acute leukemia. It is suggested that not G
      CSF alone but G-CSF with infection could induce remission, which might be related
      to a differentiation effect of G-CSF in this case. G-CSF is not only safe but
      also useful for remission induction therapy in hypoplastic acute leukemia.

PMID- 9644303
TI  - Accelerated phase of chronic myeloid leukemia presenting with hypercalcemia and a
      mediastinal mass.
AB  - A patient with chronic myeloid leukemia developed hypercalcemia as a presenting
      sign of the accelerated phase of the disease. Ultrasound of the neck showed a
      large hypodense mass connected to the thyroid gland, which was thought to be a
      parathyroid tumor and the cause of the hypercalcemia. Histology of the surgically
      removed mass revealed a chloroma. The patient's course was complicated by
      respiratory failure and metastatic calcinosis of the lung, an unusual finding in
      hypercalcemia of short duration.

PMID- 9644304
TI  - Reference values for bisphosphoglycerate mutase protein content and specific
      activity in human erythrocytes.

PMID- 9644305
TI  - Haemostasis, thrombosis, and endothelium in Behcet's disease.

PMID- 9644306
TI  - [Recent progress of matrix metalloproteinase (MMP) research and its clinical
      application for cancer therapy].
AB  - The matrix metalloproteinases (MMPs) are a family of secreted and membrane-bound
      zinc-endopeptidases. These enzymes are capable of degrading the extracellular
      matrix, including collagens, laminin, proteoglycan and fibronectin. In some human
      cancers, a positive correlation has been demonstrated between MMP expression and
      the likelihood of developing metastasis. An imbalance between MMPs and the
      tissues inhibitor of metalloproteinases (TIMPs) may play a significant role in
      the invasive phenotype of cancers. Although TIMPs have been shown to inhibit
      tumor metastasis in some in vivo models, they are not suitable for pharmacologic
      applications due to their short half-life in vivo and large molecular size. In
      this paper, recent advances in MMP research and reports of clinical applications
      of synthetic MMP inhibitors for cancer patients are reviewed.

PMID- 9644308
TI  - [Risk factors in aged patients undergoing gastrointestinal cancer operations].
AB  - With the rapid increase in the elderly population in Japan and the continued
      advances in perioperative management and operative techniques, more surgical
      procedures will be performed in the geriatric patients. The loss of reserve
      capacity and associated disease in the elderly patients may lead to an
      inappropriate response to surgical stress, resulting in high morbidity and
      mortality. Therefore, the identification of surgical risk is imperative in the
      surgical care of aged patients. The risk factors in the aged include
      malnutrition, anemia, cerebrovascular disease, hepatic disorders and
      immunosuppressive therapy. This review focuses on the risk factors and simple
      method to estimate the surgical risk in aged patients undergoing gastrointestinal
      cancer surgery.

PMID- 9644309
TI  - [Cancer chemotherapy in patients of advanced age (over 75)].
AB  - Generally, elderly patients are excluded from therapeutic trials because of
      decreased tolerance to chemotherapy. We discussed chemotherapy cancer patients of
      an advanced age based on our experience of malignant lymphoma and advanced
      gastric cancer patients over 75 years of age. We found the tendencies for
      diagnosis at more advanced stages involved many complications, especially 10% of
      cases have double cancer, and not good performance status in these patients. Some
      53 cases of malignant lymphoma were treated with combination chemotherapy
      including anthracycline, obtained prolongation of survival in responder. On the
      other hand, 64 cases of advanced gastric cancer were treated with palliative
      chemotherapy. Some clinical trials have showed that older and younger patients
      were no different in terms of response, toxicity and overall survival. But these
      selected elderly patients could be entered in clinical trials, seemed to have to
      have surprisingly good health, no historical complications and good performance
      status, in spite of suffering from cancer. Not only chronological age but also
      the kinds of cancer and performance status are important justification for
      decisions to limit or withhold treatment.

PMID- 9644310
TI  - [Radiotherapy for elderly patients].
AB  - Radiotherapy is of particular benefit to elderly patients as alternative surgery,
      and it is widely used with curative and palliative intent. Patients aged 75 and
      older accounted for 5-10% of all cases, and half of them had some complications.
      Radical radiotherapy was performed in 63-73% of the elderly patients and 88-100%
      were able to complete the planned course. Several authors reported that the
      elderly patients adequately staged, can tolerate radical radiotherapy and have
      survival comparable to that of younger patients. But careful management is
      needed.

PMID- 9644311
TI  - [Treatment of prostate cancer in patients aged 75 or older].
AB  - In view of the increasing incidence and mortality rate of prostate cancer in
      Japan, the management of elderly patients with prostate cancer is an important
      issue now. We therefore analyzed the clinicopathological features and long-term
      outcomes of 182 patients with prostate cancer, aged 75 or older, in order to
      establish the treatment strategy for this age group of patients. There were more
      patients with advanced disease (stage C-D) than those with localized disease
      (stage A2-B), and the patients with moderate to poorly differentiated tumors were
      more numerous than those with well-differentiated tumors. The overall survival
      curve of the patients with localized prostate cancer was in line with the age
      matched expected survival curve, while that with advanced prostate cancer was far
      below the expected survival curve. These results demonstrated that advanced
      prostate cancer in elderly patients is as harmful as in younger patients,
      indicating the necessity for early detection and treatment of prostate cancer
      among the younger generation. On the other hand, localized prostate cancer in
      elderly patients should be treated less invasively to maintain their quality of
      life.

PMID- 9644312
TI  - [Treatment of gynecologic cancer in elderly patients].
AB  - Due to the increasingly elderly population and prolonged life span of women in
      Japan, population of women older than 75 years of age has become 7.3% of all
      female population in 1995. According to this change, elderly patients with
      gynecologic malignancies, such as cervical cancer, endometrial cancer and ovarian
      cancer have increased markedly. Those patients tend to have progressed disease
      and therefore treatments should be less invasive and tailored based upon
      individual conditions to maintain their quality of life.

PMID- 9644313
TI  - [Cancer chemotherapy in patients older than 75 years old--from the aspect of
      clinical pharmacology].
AB  - A review concerning cancer chemotherapy in older patients from the aspect of
      clinical pharmacology was performed. Age-related physiological changes, comorbid
      disease, polypharmacy, and social issues are major problems in older patients
      with cancer. Pharmacokinetics of anticancer agents change according to
      physiological changes, and distribution, metabolism and excretion may change.
      Resistance to anticancer agents is more common. Side effects are more severe and
      frequent because of age-related physiological changes and comorbid disease. Since
      the interindividual difference is large in the elderly, the individual dose of
      anticancer agents must be determined especially for patients older than 75 years
      old.

PMID- 9644314
TI  - [Phase II study of KRN8602 (MX2) for malignant lymphoma].
AB  - We performed a clinical phase II study of KRN8602, a new anthracycline
      derivative, for relapsed or recurrent malignant lymphoma. KRN8602 was given at
      doses of 12-15 mg/m2 for 3 consecutive days, repeating every 3-4 weeks. Among 44
      patients entered into the study, 36 were evaluable for safety, and 35 were
      evaluable for efficacy. The response rate was 18.2% (6PR/33) for non-Hodgkin's
      lymphoma and 0% (0/2) for Hodgkin's disease. Major toxicities were bone marrow
      suppression and gastrointestinal toxicity. Leukopenia was observed in 77.8%,
      thrombocytopenia in 44.4%, hemoglobin decrease in 44.4%, nausea and vomiting in
      94.4% and anorexia in 80.6%. However, all toxicities were clinically manageable.

PMID- 9644315
TI  - [Thymidylate synthase expression in patients with hypopharyngeal carcinoma].
AB  - We analyzed the relationship between clinical response to neo-adjuvant
      chemotherapy including 5-fluorouracil (5-FU) in patients with hypopharyngeal
      carcinoma (HPC) and thymidylate synthase (TS) expression in their tumors. TS
      expression was evaluated with immunohistochemical staining techniques on biopsy
      specimens from HPC patients. TS immunostaining was divided into four levels (TS0
      TS3) according to its level and pattern. The relationship between prognosis,
      tumor size, nodal status, differentiation of tumor cells and TS expression were
      also investigated. There was a statistically significant association between the
      level of TS expression and tumor size (p < 0.01). In terms of the effectiveness
      of chemotherapy, tumor differentiation, nodal status and prognosis, a statistical
      difference was not found in TS expression. These results suggest that the level
      of TS expression may show the degree of tumor proliferation, but may not
      necessarily be useful to obtain a response to chemotherapy including other drugs,
      e.g., cisplatin and other derivatives of platinum.

PMID- 9644316
TI  - [Comparative study on quality of life between weekly and monthly chemotherapy
      with cisplatin, vindesine and mitomycin C in patients with non-small cell lung
      cancer].
AB  - A comparative study between weekly and monthly chemotherapy with CDDP, VDS and
      MMC was performed on the basis of QOL in patients (stage III A/III B/IV) with non
      small lung cancer from September 1993 to August 1996. Arm A received CDDP (80
      mg/m2) monthly on day 1, VDS (3 mg/m2) on days 1 and 8, MMC (8 mg/m2) on day 1.
      Arm B received CDDP (40 mg/m2), VDS (3 mg/m2) and MMC (4 mg/m2) on day 1, and
      followed by CDDP (20 mg/m2), VDS (1.5 mg/m2) and MMC (2 mg/m2) weekly. A diary
      type QOL self-rating questionnaire was devised for this study, consisting of 5
      scales including 13-item questionnaires and a face scale as the global scale.
      Chronological QOL data from 20 days during chemotherapy (total dose of CDDP was
      80 mg/m2 in both A and B arm) were analyzed using summary measures. In the 78
      eligible subjects of the study, 34 were QOL subjects of the 27 eligible subjects,
      13 were in arm A and 14 in arm B. 1. The questionnaire was confirmed to be
      satisfactory with regard to reliability and validity as a questionnaire for the
      evaluation of this study by factor and correlation analysis. 2. Although each
      scale changed to the worth level after chemotherapy, there was no significant
      difference between arm A and B. 3. Summary statistics were assessed using indices
      of the area under the curve (AUC) and the maximum fluctuations of QOL scores (Dif
      max) arm B showed a tendency to smaller changes than arm A in AUC and Dif max.
      There was a significant difference in the physical well-being scale of Dif max.
      4. Three items, including the physical well-being in arm B, revealed a better
      score than those of arm A. Abdominal condition showed a significant difference
      between the two arms. 5. No obvious difference in anti-cancer effectiveness was
      found between arm A and B. Arm B showed a longer median survival, less nausea and
      vomiting, leukopenia and thrombocytopenia compared with arm A. The above results
      suggested that weekly chemotherapy is as effective, less toxic and shows less
      influence against patients QOL than the conventional monthly chemotherapy in this
      study.

PMID- 9644317
TI  - [A cooperative study on concomitant with low-dose divided administration of
      cisplatin (CDDP) and sustained drip infusion of 5-fluorouracil (5-FU) for
      unresectable advanced gastric cancer. Osaka Cisplatin Gastric Cancer Study
      Group].
AB  - For patients with unresectable gastric cancer registered between July 1994 and
      September 1995, the following dosage regimen was examined: a drip infusion of
      cisplatin (CDDP) at 7 mg/m2/day for 5 consecutive days and 2-day withdrawal a
      week for 3 weeks with concomitant sustained drip infusion of 5-FU at 300
      mg/m2/day for 21 days. The whole cycle was repeated again after 2-week
      withdrawal. The antitumor effect was seen in 39.4% among 33 cases. With respect
      to histological classification, there was no difference in appearance of the
      effect between the moderately differentiated type at 62.5% and the low
      differentiated type at 42.9%. The cases which became resectable after the
      administration included those in which the tumor disappeared completely in the
      resected specimens. As adverse reactions encountered in the cases above Grade 3,
      anorexia, nausea and vomiting and diarrhea were seen as clinical symptoms in 10,
      5.3 and 11.8%, respectively. As laboratory test values, decrease in hemoglobin,
      leukocytopenia and thrombocytopenia were seen in 16.7, 15.8 and 5%, respectively,
      while renal or liver dysfunction did not occur. This dosage regimen was
      considered useful for unresectable advanced gastric cancer, although
      myelosuppression should be watched carefully.

PMID- 9644318
TI  - [Anticancer drug intraperitoneal chemotherapy using T-type reservoir sheet for
      unresectable gastric cancer].
AB  - T-type reservoir sheets (anti-adhesion sheets developed to prevent adhesions +
      reservoir) were intraperitoneally implanted in 16 patients with unresectable
      gastric cancer and postoperatively used to suction off ascitic fluid, to prevent
      cancerous adhesions of the intestines, and to intraperitoneally infuse anticancer
      drugs with a view to improving QOL and prolonging survival time. The results
      showed that whereas all of the patients had been class V according to
      intraoperative cytodiagnosis, postoperatively they were all class I-II and their
      ascites had either completely or temporarily resolved. Performance status (PS)
      improved in 14 patients (87.5%), and 14 patients (87.5%) were discharged.
      According to the Cancer Body Cavity Efficacy Rating Criteria (Japan Society for
      Cancer Therapy), CR was achieved in 10 cases, PR in 3 cases, NR in 3 cases, and
      the mean home care rate was 45.4%. Mean survival time to date, February 1997, is
      7.8 months, two patients are alive, and the longest survival time has been 22
      months. This method facilitates suctioning of ascitic fluid. It prevents
      irregular adhesions of the intestine, and protects against the development of
      ileus. It enables repeated intraperitoneal administration of high concentrations
      of anticancer drugs, uniformly, extensively, safely and easily. It facilitates
      intraperitoneal cytodiagnosis, ascitic fluid sampling, and monitoring of the
      efficacy of anticancer agents. The special features of this method are the high
      percentage of patients residing at home and the ability to administer
      intraperitoneal infusions of anticancer agents continually and repeatedly on an
      outpatient basis.

PMID- 9644319
TI  - [An early phase II clinical study of S-1 in patients with breast cancer. S-1
      Cooperative Study Group (Breast Cancer Working Group)].
AB  - An early phase II clinical study of S-1 in patients with advanced or recurrent
      breast cancer was undertaken by a cooperative study group (Breast Cancer Working
      Group) of 14 institutes in Japan. S-1 was administered twice daily at 75 or 50 mg
      (dose FT)/body for 28 consecutive days with 14 days rest (one course). Twenty
      eight patients were enrolled, 27 were eligible for the study, and 25 were
      evaluable for efficacy. Four complete responses and seven partial responses were
      obtained, and the response rate was 40.7% (11/27) [ninety percent confidence
      interval for this response was 26.7-56.4%]. The major adverse reactions observed
      were myelosuppression represented by leukopenia 44.4% (12/27), neutropenia 40.7%
      (11/27), RBC decreased 37.0% (10/27), hemoglobin decreased 29.6% (8/27), anorexia
      55.6% (15/27), nausea/vomiting 48.1% (13/27), and fatigue 33.3% (13/27). The
      results suggested that the efficacy and safety of S-1 were effective against
      advanced or recurrent breast cancer. The objective of study judged should be
      investigated in a late phase II clinical study.

PMID- 9644320
TI  - [Late phase II study of TAT-59 (miproxifene phospate) in advanced or recurrent
      breast cancer patients (a double-blind comparative study with tamoxifen
      citrate)].
AB  - The efficacy and safety of TAT-59 (miproxifene phospate) were compared with
      tamoxifen citrate (TAM) in ER-positive or ER-unknown patients with advanced or
      recurrent breast cancer, using the double-blind method. TAT-59 and TAM were both
      given 20 mg/body orally for over 12 weeks in daily doses. Eligible cases were 93
      in the TAT-59 group and 102 patients in the TAM group. The response rate was
      shown to be 30.1% (28/93) in the TAT-59 group and 26.5% (27/102) in the TAM
      group. Statistical equivalence between both treatments was proven at 90%
      confidence interval (-8.5% < or =, < or = 12.8%). Adverse reactions observed in
      the patients receiving TAT-59 were hot flush, nausea and vomiting, sweating,
      anorexia, abnormal values in liver function tests, and anemia, showing no
      differences from the TAM group. Leukopenia (4.9%) and thrombopenia (2.9%)
      reactions were found only in the TAM group. Two patients in the TAT-59 group and
      three in the TAM group discontinued treatment due to adverse reactions. However,
      these adverse reactions were reversible in both groups. In conclusion, TAT-59 was
      showed comparable efficacy and safety with TAM in ER-positive or ER-unknown
      patients with advanced or recurrent breast cancer.

PMID- 9644321
TI  - [A case of adenoid cystic carcinoma in epipharynx which responded to radiation
      and chemotherapy].
AB  - A 45-year-old man visited our hospital complaining of a right hearing loss. The
      head and neck examination was unremarkable except for right secretory otitis
      media. Fiberoptic examination of the nose and the epipharynx revealed a mass.
      Transnasal biopsy was performed and histologic analysis revealed adenoid cystic
      carcinoma. Invasion of the sphenoid sinus was identified by MRI. He was treated
      with FAR therapy (5-FU, Vit A, Radiation) and chemotherapy (intra-arterial
      infusion of ADM). Severe side effects were not seen during treatment. After
      treatment, the majority of the tumor mass disappeared on fiberoptic examination
      and MRI. On repeat biopsy specimens, no cancer cells were found. The patient was
      alive with no evidence of disease as of August 1997.

PMID- 9644322
TI  - [A case of hepatocellular carcinoma with reduction of primary tumor and
      disappearance of multiple lung metastasis].
AB  - A 56-year-old male had suffered from hepatocellular carcinoma treated by
      operation, PHoT and TAE since 1994. In December 1995, he had multiple metastases
      of lung in addition to recurrence of primary hepatic lesions. We discontinued
      treatment of TAE and decided to administer UFT (400 mg/day) orally as an
      outpatient. After seven months, the primary hepatic lesions were decreased in
      size, and metastatic lesions of lung were completely eliminated with reduction of
      AFP level. Generally, hepatocellular carcinoma with metastasis is refractory to
      treatment. However, this result suggests that UFT is one of the effective
      treatments for such advanced cases as having lung metastasis.

PMID- 9644323
TI  - [Complete disappearance of metastatic pulmonary tumors in a case of
      hepatocellular carcinoma treated with UFT].
AB  - The disappearance of multiple pulmonary metastatic lesions in hepatocellular
      carcinoma patient following the oral administration of UFT is reported. Pulmonary
      and pelvic metastases were detected in a 71-year-old female hepatocellular
      carcinoma patient treated by TAE (Trans-Arterial Embolization with epirubicin,
      mitomycin C, lipiodol and Gelform) three times in one year. Four months after
      beginning oral administration of UFT-E granule 1.5 g/day (tegafur 300 mg/day,
      uracil 672 mg/day), three pulmonary metastatic lesions markedly reduced in size,
      and disappeared completely 6 months after beginning UFT. A pelvic metastatic
      tumor markedly reduced in size by the combined effect of radiation, TAE
      (epirubicin, mitomycin C, lipiodol, Gelform) and oral UFT. We consider UFT was
      effective in the disappearance of multiple pulmonary metastatic lesions, because
      three TAE administrations of epirubicin and mitomycin C could not prevent
      systemic spreading of hepatocellular carcinoma.

PMID- 9644324
TI  - [A case of renal pelvic cancer with recurrence of liver metastasis showing
      partial response by injection of methotrexate and intraarterial infusion of
      cisplatin and pirarubicin].
AB  - The patient was a 71-year-old man who had been diagnosed as having a left renal
      pelvic cancer with liver metastasis. We performed total left nephroureterectomy
      with lymphnode cleaning and partial resection of the liver. Because abdominal CT
      5 months after the operation revealed multiple metastasis of the liver, we
      performed chemotherapy with a regimen consisting of methotrexate 50 mg
      (intravenous injection), cisplatin 30 mg and pirarubicin 20 mg (intraarterial
      infusion), and leucovorin 3 mg (intramuscular injection), three times at
      intervals of 6 hours. Ten days after chemotherapy, CT revealed the disappearance
      of most of the liver metastatic lesions, and a partial response was obtained. We
      are now performing the regimen at an interval of a month to a month and one-half
      to control the metastatic lesions.

PMID- 9644325
TI  - [Experimental study of intraperitoneal hyperthermic chemotherapy].

PMID- 9644326
TI  - [Proposals for revisions of UICC TNM system (1997)--breast cancer].
AB  - The TNM system for classification and staging approved by Union Internationale
      contro le Cancer (UICC)/TNM Committee is designed primarily for patient care and,
      in this context, is equally applicable to patients in clinical research,
      community hospitals, and developing countries. It is clearly evident to all who
      have been involved that international agreement on the classification of cancer
      at all anatomical sites is exhilarating, since data from around the world can
      finally be compared with validity. The UICC believes that the TNM system can
      fulfil the following five objectives: (1) aid in the planning of treatment; (2)
      give an indication of prognosis; (3) assist in evaluation of the results of
      treatment; (4) facilitate the exchange of information between centres; and (5)
      contribute to the continuing investigation of human cancer. The important
      questions for planning of treatment (1), however, can not be answered by the
      information of the clinical TNM stage as the concept in the Japanese Joint
      Committee. The knowledge of the TNM stage does not yield information of
      prognostic importance (2). More accurate indices of prognosis can be calculated
      from multivariate analysis to examine many clinicopathological variables, and
      biological markers along with patient age and nodal status. The analysis makes
      the difficulties for the results of treatment due to the large number of
      combinations with T and N subgroups (3) (4). According to the fifth objective (5)
      of TNM classification, we would like to propose a more simple and pragmatic
      classification by classifying patients into those requiring surgical approach and
      adjuvant therapy.

PMID- 9644327
TI  - Reactive oxygen species and silica-induced carcinogenesis.
AB  - Although silica has recently been designated as a carcinogen, its mechanism of
      carcinogenesis is not fully understood. Recent studies suggest that free-radical
      reactions may play an important role in the initiation and progression of cancer.
      This article summarizes literature on the generation of reactive oxygen species
      (ROS) directly from silica and from silica-stimulated cells. It also summarizes
      information concerning the role of ROS in silica-induced DNA damage as well as in
      silica-induced cell proliferation, including the effects of silica on the
      activation of nuclear transcription factors, induction of growth factors and
      oncogene expression, redox regulation of the p53 tumor suppressor gene, induction
      of apoptosis, and division of damaged cells. Understanding the role of ROS in
      silica-mediated reactions may help develop therapeutic agents to block silica
      induced free radical reactions and thus prevent or attenuate silica-induced
      carcinogenesis.

PMID- 9644328
TI  - Developmental and reproductive toxicity of inorganic arsenic: animal studies and
      human concerns.
AB  - Information on the reproductive and developmental toxicity of inorganic arsenic
      is available primarily from studies in animals using arsenite and arsenate salts
      and arsenic trioxide. Inorganic arsenic has been extensively studied as a
      teratogen in animals. Data from animal studies demonstrate that arsenic can
      produce developmental toxicity, including malformation, death, and growth
      retardation, in four species (hamsters, mice, rats, rabbits). A characteristic
      pattern of malformations is produced, and the developmental toxicity effects are
      dependent on dose, route, and the day of gestation when exposure occurs. Studies
      with gavage and diet administration indicate that death and growth retardation
      are produced by oral arsenic exposure. Arsenic is readily transferred to the
      fetus and produces developmental toxicity in embryo culture. Animal studies have
      not identified an effect of arsenic on fertility in males or females. When
      females were dosed chronically for periods that included pregnancy, the primary
      effect of arsenic on reproduction was a dose-dependent increase in conceptus
      mortality and in postnatal growth retardation. Human data are limited to a few
      studies of populations exposed to arsenic from drinking water or from working at
      or living near smelters. Associations with spontaneous abortion and stillbirth
      have been reported in more than one of these studies, but interpretation of these
      studies is complicated because study populations were exposed to multiple
      chemicals. Thus, animal studies suggest that environmental arsenic exposures are
      primarily a risk to the developing fetus. In order to understand the implications
      for humans, attention must be given to comparative pharmacokinetics and
      metabolism, likely exposure scenarios, possible mechanisms of action, and the
      potential role of arsenic as an essential nutrient.

PMID- 9644329
TI  - Influence of caloric intake on aging and on the response to stressors.
AB  - Reducing the food intake of rodents to well below that of ad libitum fed animals
      increases the life span. This action, which gerontologists often refer to as the
      antiaging action of dietary restriction (DR), is due to the slowing of the aging
      processes. DR also maintains most physiological processes in a youthful state and
      delays the occurrence and/or slows the progression of age-associated disease
      processes. This antiaging action of DR results from the reduced intake of
      calories. Reduction of the body fat content does not play a causal role in the
      antiaging action of DR, nor does reduction in the metabolic rate. Alterations in
      the characteristics of carbohydrate metabolism and of oxidative metabolism in
      response to DR have been found that are of such a nature that they could, at
      least in part, underlie the antiaging action. Several theories have recently been
      proposed in regard to the mechanisms responsible for the antiaging action of DR,
      but none has been tested by rigorously designed studies. Of these theories, the
      one that seems most promising is based on the fact that DR protects rats and mice
      of all ages against the damaging actions of acute stressors. This protective
      action against stressors may play a major role in the antiaging action of DR.

PMID- 9644330
TI  - Improving the U.S. EPA Toxic Release Inventory database for environmental health
      research.
AB  - In 1986, Congress passed the Emergency Planning and Community Right-to-Know Act
      (EPCRA) in response to the tragic death of thousands of people in Bhopal, India,
      following the accidental release of the toxic gas methyl isocyanate (MIC) from a
      Union Carbide facility. As a component of EPCRA, certain manufacturers are
      required to report annually the total mass (pounds per year, lb/yr) of toxic
      chemicals released into the environment (air, water, land, or underground
      injection), treated on-site, or shipped off-site for further waste treatment.
      This information is compiled by the U.S. Environmental Protection Agency (EPA)
      into a publicly accessible database known as the Toxic Release Inventory (TRI).
      The TRI database is designed to encourage pollution prevention and waste
      reduction by increasing public access to and knowledge of environmental chemical
      releases. EPCRA has been generally considered by industry, government, and
      community representatives as one of the most successful environmental laws in
      U.S. history. Over the past few years, EPA has initiated a three-phased expansion
      to EPCRA reporting requirements that will enhance the overall usefulness of the
      TRI database. The focus of this article is to discuss these changes and highlight
      several current uses of the TRI database in environmental health research.

PMID- 9644331
TI  - Nurse practitioners.

PMID- 9644332
TI  - Chemoprophylaxis.

PMID- 9644333
TI  - To have and to hold: nursing information in the 1990s and beyond.
AB  - Within contemporary nursing a tension exists between the need to develop nursing
      related databases, and the philosophical underpinning of current nursing care.
      The arguments 'for' include the need to counteract the substitution of nurses by
      care attendants, the move towards evidence-based practice, and an increasing use
      of information technology in health care. Arguments against include the
      philosophies of holism, the reliance of nurse clinicians on verbal communication,
      the complexity of nursing data, and cumbersome nature of contemporary information
      systems. In a healthcare context where the value of nursing must be demonstrated,
      nurses will need to explore avenues that capitalise on the benefits offered by
      the establishment of nursing specific data bases, without compromising the
      preferred standard of nursing care. It is timely that contemporary activities
      designed to establish common nursing data sets be reviewed. Nursing minimum data
      sets, unified nursing languages, and more recent approaches including natural
      language systems, conceptual graphs, multi-axial taxonomies and multi media
      interfaces, make up an often confusing potpourri of approaches. The intention of
      this paper is to provide explanations and examples of each approach in an effort
      to reduce confusion and stimulate further debate.

PMID- 9644334
TI  - "I want my mummy". Changes in the care of children in hospital.
AB  - The Welfare of Sick Children in Hospital' was the formal title of a report
      published in Britain in 1959 which came to be known as the Platt Report, after
      Sir Harry Platt, the chairman of the parliamentary committee which investigated
      the care of children in hospital. The committee found the hospitals were
      miserable places for children, where they were expected to conform to ward
      routines, not allowed to play; where to lie quietly was the accepted norm, and
      where, under no circumstances, were the parents allowed to visit outside the
      declared visiting hours. Subsequent to the publication of the Platt Report a
      revolution occurred in children's hospitals in Britain and other western
      countries, including Australia. This paper explores these changes, and discusses
      implications for paediatric care in hospitals and paediatric nursing education
      today.

PMID- 9644335
TI  - Tracing the tax maze.

PMID- 9644336
TI  - The female factory at Parramatta 1804-1850s.
AB  - In the first few decades following the arrival of the First Fleet in 1788 there
      came to be established three institutions in the young colony referred to as
      female factories. The first was established at Parramatta in 1804 (Schultz, 1991:
      4, 11-13) and the other two in 1827, one in Hobart (Schultz, 1991:32, 69) and the
      other in Moreton Bay (Schultz, 1991:41). This is a brief account of the salient
      features in the development of the first female factory which highlights the
      status of women in that early society. In preparing the account I have drawn
      heavily on Schultz's 'A Tapestry of Service' and Salt's 'These Outcast Women.'

PMID- 9644337
TI  - Changing technology in health: product liability.
AB  - Greater health consumer awareness and increasing levels of concern for the rights
      of patients have led to patient care technology being more strictly regulated.
      This article analyses both the general law issues and the particular statutes
      that will be of relevance to those involved in evaluating and implementing such
      technologies. There are three main elements to this analysis. Firstly, there is
      the issue of liability for a product fault, which will in many cases be directed
      by legislation back to the manufacturer of the goods. Secondly, those involved in
      placement of patient care technology should be aware of anti-discrimination
      legislation when making placement decisions. Finally, occupational health and
      safety legislation sets minimum standards for technology used in healthcare
      facilities. The author suggests ways of complying with the laws for each
      regulatory regime.

PMID- 9644338
TI  - Theoretical perspectives on narrative inquiry.
AB  - Narrative inquiry is gaining momentum in the field of nursing. As a research
      approach it does not have any single heritage of methodology and its
      practitioners draw upon diverse sources of influence. Central to all narrative
      inquiry however, is attention to the potential of stories to give meaning to
      people's lives, and the treatment of data as stories. This is the first of two
      papers on the topic and addresses the theoretical influences upon a particular
      narrative inquiry into nursing scholars and scholarship. The second paper,
      Conducting a narrative analysis, describes the actual narrative analysis as it
      was conducted in this same study. Together, the papers provide sufficient detail
      for others wishing to pursue a similar approach to do so, or to develop the ideas
      and procedures according to their own way of thinking. Within this first
      theoretical paper, perspectives from Jerome Bruner (1987) and Wade Roof (1993)
      are outlined. These relate especially to the notion of stories as 'imaginative
      constructions' and as 'cultural narratives' and as such, highlight the profound
      importance of stories as being individually and culturally meaningful. As well,
      perspectives on narrative inquiry from nursing literature are highlighted.
      Narrative inquiry in this instance lies within the broader context of
      phenomenology.

PMID- 9644339
TI  - The art of poster presentation.
AB  - Need to attract attention with a captivating poster? This article provides
      helpful suggestions for the design and production of a poster. Layout, colour,
      balance, lettering and the use of pictures are considered. Details are also
      provided of the Research-poster Appraisal Tool (R-PAT) developed by Bushy (1991).
      The authors recommend that poster presenters use the tool to self-assess
      effectiveness prior to presentation. The tool can also be used by conference
      organisers for rating displayed posters.

PMID- 9644341
TI  - Web-site review: rural health.

PMID- 9644340
TI  - Legionellae.
AB  - Legionellae cannot be eradicated from the water supply, since they are naturally
      occurring and ubiquitous. Routine bacteriologic culturing of man made aquatic
      environments is not recommended (Soule et al 1995). Therefore any water use that
      results in production of aerosols should be regularly evaluated to ensure the
      source has not been contaminated with the bacteria. Any aerosolised water
      entering a sterile area such as the lungs should be sterile. Tap water should not
      be used to rinse any respiratory therapy equipment. Routine maintenance of water
      supplies to eliminate sediment and scale from tanks and trays is essential
      (Benenson 1995, Lowry & Tompkins 1993). Australian & New Zealand Standard AS/NZ
      3666-1995 Parts 1 and 2 outline these requirements.

PMID- 9644342
TI  - Megan Jane Johnstone.

PMID- 9644343
TI  - Historical development of outcomes-based care delivery.
AB  - Outcomes-based care delivery is both a subtle and profound change in practice. It
      is proactive, patient-centered, data-generating, and establishes clear
      accountability. Most importantly, outcomes defined and managed at the patient
      provider level will be the quality conscience as health care enters a new
      millennium.

PMID- 9644344
TI  - The Vanderbilt model of outcomes management.

PMID- 9644345
TI  - The clinical resource management model.
AB  - The clinical resource management model is a highly successful method of
      redesigning operations to focus on reducing costs while improving quality. In
      these dynamic days in our medical centers it is important to maintain quality
      standards while implementing cost reductions. Through careful analysis of our
      practice we can learn from our best practicing providers and build systems to
      replicate their example. By improving our processes of care we meet the
      expectation of the public and our regulators through process improvement in a
      collaborative, multidisciplinary manner.

PMID- 9644346
TI  - Longitudinal outcomes measurement and management. Standardized practices across
      the continuum of care.
AB  - Longitudinal outcomes measurement involves collection of outcomes data across a
      continuum of care services in a patient cohort. Measurement and management of
      intermediate outcomes, within the varied care settings represented by the
      continuum, must precede measurement of long-term outcomes to provide meaningful
      information to providers. Once connected across a continuum of services,
      longitudinal outcomes measures produce powerful findings that may be used to
      successfully optimize the health care experience for patients and their families.
      The postacute continuum is ripe with research opportunities and should be pursued
      with vigor by outcomes researchers interested in understanding the contributions
      of this segment of the continuum to the production of patient outcomes.

PMID- 9644347
TI  - The concept and the development of chest pain emergency departments as a strategy
      in the war against heart attack.
AB  - Critical nurses in the CPED can have a very fulfilling role in expanding their
      influence within the hospital setting, as well as within the community to become
      part of the needed change to significantly reduce deaths from MI in the United
      States. The mission impossible becomes possible when critical care nurses are
      part of this challenging process. Nowhere can these efforts be better started
      than in emergency department committed to continuous quality improvement changes
      under this new paradigm. The person who can best help make this strategy work the
      best is the critical care nurse in charge.

PMID- 9644348
TI  - Outcomes management for interventional cardiology.
AB  - In the evolution of quality assessment activities in interventional cardiology,
      outcomes management has become the benchmark for demonstrating optimal care. The
      high volume of interventional cardiology procedures performed each year mandates
      that efficient, high-quality and cost-effective patient care be delivered to all
      patients with cardiovascular disease. Although the interventional cardiology
      procedures represent only a snap shot of the patient's management of coronary
      artery disease, a long-term plan for positive outcomes is required. A
      multidisciplinary approach to outcomes management facilitates institutions to be
      competitive in today's health care market.

PMID- 9644349
TI  - Port-access cardiac surgery protocols and early outcomes.
AB  - As a new cardiac surgical procedure, port-access holds promise to significantly
      impact the surgical approaches for treatment of CAD. Supporting collaborative
      practice protocols contributes to early extubation, rapid in-hospital recovery,
      and shortened LOS. Discharge protocols address postoperative concerns. Early
      results suggest that patient recovery is shorter than the time for conventional
      procedures; patients are able to return to an active lifestyle that is beneficial
      to families, patients, and employers.

PMID- 9644350
TI  - Impact of a critical care pathway for unstable mechanically ventilated patients.

PMID- 9644351
TI  - The long-term mechanically ventilated patient. An outcomes management approach.
AB  - As noted previously, prior to permanently instituting an outcomes approach, we
      compared the effects of such a model to a nonoutcomes-managed approach. The
      positive trend noted during the study interval has been sustained 2 years later,
      and the variables of cost, LOS, and ventilator duration (median = 9 days for DRG
      475, 483 combined) for these patients continue to be favorably affected (see
      Figure 2). In addition, the outcomes-management model has been well accepted by
      all members of the health care team. The outcomes manager is a respected and
      valued member of the team and is central to the ongoing success of the approach.
      Although the clinical pathway is an essential tool for focusing and delineating
      multidisciplinary best-practice, the pathway (and processes of care contained
      within) must be continually evaluated and changed as needed. The pathway cannot
      be static if care is to be progressive. Essential to the process is a method of
      collecting and processing data in a timely way. Further, it is important that
      data collection, while important, not be the focus of the role of outcomes
      manager. Instead, the focus is the delivery of timely and effective care. Our
      current outcomes model applies to management of patients beyond the boundaries of
      the MICU or pulmonary suite. In other words, once weaned and transferred to a
      regular floor the outcomes manager no longer manages the patients (although she
      does track selected outcomes). Management of patients throughout hospitalization
      is a future goal, but we are convinced that this cannot be accomplished by a
      single outcomes manager. Although we are aware that other outcomes models do
      follow patients throughout the continuum of hospitalization and beyond, our
      highly clinically interactive model precludes that possibility. We are currently
      considering other similar unit-based positions to provide the desired continuity
      following discharge from the MICU or pulmonary suite. Despite our enthusiasm for
      the outcomes-management model, we recognize that other models may also result in
      comparable, favorable outcomes. It is important that those who adopt similar
      models of care delivery for managing patients requiring prolonged ventilation be
      scientific in their approach. Long-term studies of the efficacy of these models
      are essential if we are to truly provide quality care for our patients in the
      future. Unfortunately, as noted earlier, bias will be hard to overcome. Hospitals
      vested in rapidly establishing a stable financial bottom-line are likely to
      embrace quick applications. Projects with a true experimental design to evaluate
      efficacy, such as this one, will be rare in these organizations. Finally, it is
      critical that variables of interest be inclusive of specific quality indicators
      such as ventilator duration and complications rather than global institutional
      markers such as LOS. Standardization of variables of interest is imperative if
      outcomes are to be compared. For example, patients requiring long-term mechanical
      ventilation are identified by the AACN's Third National Study Group on weaning as
      those who require mechanical ventilation for more than 3 days. If we are to
      compare other variables of interest such as total ventilator duration, such as
      definition is essential or we will be comparing apples and oranges in the future.
      Provision of quality, cost-effective care for patients requiring prolonged
      ventilation is a true clinical challenge. Outcomes management is a
      multidisciplinary method of care delivery that is systematic and comprehensive in
      approach. Although little science exists related to the application of the model
      for patients requiring prolonged ventilation, preliminary reports are promising
      and warrant future applications and evaluation of the same.

PMID- 9644352
TI  - Outcomes management for stroke patients using thrombolytics.
AB  - In the current health care market, there is a sharp awareness by both consumers
      and managed care providers that hospitals are only as good as the outcomes they
      can produce. Collaboration among disciplines that provide services, in this case
      treatment for stroke has enhanced patient outcomes. The synergy that has
      developed among those involved has thus far created a win-win situation. The key
      to successful outcomes is to have all those involved possessing a clear picture
      of their role, accepting it, and taking ownership of it.

PMID- 9644353
TI  - Impact of technology on costs and patient outcome.
AB  - Technology is only as effective as the clinicians who employ the technology and
      the system in which they function. For any technology to change patient outcome,
      or be cost effective, clinicians must be educated and incented to change their
      practice. At this point in American health care, technology appears to vary
      widely in the effectiveness in which it is employed. Research consistently
      decries the lack of effective use of technology. Some authors have claimed this
      lack of consistent use of technology is near a crisis proportion, both in terms
      of the costs and impact on patient outcome. The wide variability in technology
      application is understandable owing to the lack of a unifying approach to the
      application, education, and evaluation of technology. Only when we have an
      organized system, lead by professional societies, will technology usage achieve
      standardization. Until that time, individual hospitals need to follow guidelines
      like the ones presented in this article to ensure patients are receiving optimal
      and cost-effective care.

PMID- 9644354
TI  - Integration of acute care CNS and case manager roles.
AB  - To be effective in the new environment of managed health care, APNs must have a
      transformed outlook on providing nursing care. Accountability for day to day care
      that leads to shorter hospital stays and at the same time improves the quality of
      care is essential. The nurse's focus can no longer be on each small piece of
      care, but rather on a broad perspective of the entire continuum of care. The
      expert skills of the critical care CNS are still needed to manage the complex
      care required of patients in this setting. However, their focus needs to be
      broadened so that the larger picture remains in sight. Coordination of the
      activities of multiple care providers to achieve the ultimate goal of providing
      cost effective, quality care will be a primary responsibility of the CNS-NCM.
      This transition requires new thinking. Educational programs that include
      perspective transformation are needed for CNS role transition to become expert in
      the NCM role.

PMID- 9644355
TI  - Patient advocacy through outcomes management. A cardiac surgery example.
AB  - As we attempt to survive market forces that dominate the health care environment
      today, nurses must be active participants in finding solutions that improve
      patient care in a cost-effective manner. In our quest to reduce costs, however,
      health care providers know first-hand that good patient care is cheaper than bad,
      with its accompanying complications and readmissions. At our workplace, through
      our professional organizations, and from our political activities, nurses must
      offer a loud and unified voice towards the pursuit of patient-focused care.
      Practices such as early extubation and blood conservation are not only cost
      effective, they are clearly "the right thing to do."

PMID- 9644356
TI  - Volume lung reduction surgery: a review.
AB  - Emphysema, along with other chronic obstructive lung diseases, affects 13.5
      million Americans and is the fastest-growing cause of morbidity and mortality in
      the United States. Despite excellent medical management, there are many patients
      who become unresponsive to therapy. The current surgical options include lung
      transplantation and lung volume reduction surgery. It is important for nurses to
      be current with these new surgical techniques. This article reviews the current
      surgical procedure, postoperative complications, and patient outcomes.

PMID- 9644357
TI  - Managing latex allergy in the cardiac surgical patient.
AB  - Latex allergy affects about 1% of the general population and between 10% and 17%
      of health care workers. The severity of a latex allergic reaction can range from
      contact dermatitis to anaphylaxis and death. Critical care personnel must be able
      to identify cardiac surgical patients at risk for a latex allergy and supply
      alternative equipment, and medication. In addition, knowledge and provision of
      emergency treatment of a Type I latex reaction is paramount. Critical care staff
      need to educate both the patient and the family about latex allergy, including
      latex allergy testing and community resources.

PMID- 9644358
TI  - Minimally invasive cardiac surgery: a new frontier.
AB  - Modern cardiac surgery has been based on cardiopulmonary bypass, myocardial
      protection, aortic cross-clamping, and median sternotomy. Coronary artery bypass
      graft (CABG) has proven to be an effective treatment for patients who require
      surgical revascularization of the myocardium. Reports regarding the systemic
      effects of cardiopulmonary bypass abound in the literature. Such effects include
      hematologic, metabolic, pulmonary, cardiac, and cognitive dysfunction. Less
      invasive procedures have initiated a dramatic shift in treatment paradigms as
      well as reducing the cost of treatment. This article will discuss the MIDCAB--its
      history, a description of the surgical procedure, indications for use and patient
      selection, advantages and a perioperative plan including patient education and
      physical assessment.

PMID- 9644359
TI  - Technology utilization in the cardiac surgical patient: SvO2 and capnography
      monitoring.
AB  - Technology utilization in the cardiac surgical patient has proliferated, despite
      a lack of evidence that the technology has a positive impact on patient outcomes.
      Hospitals are left to their own efforts in deciding how and what technology to
      use. The result is an inconsistent use of technology. The use of structured
      guidelines can help hospitals improve the use of technology. Two controversial
      technologies, capnography and mixed venous oxygen saturation monitoring, are
      analyzed using this approach. It is essential for hospitals to support clinicians
      as they use methods in the evaluation and implementation of technology.
      Technology alone will not improve patient outcome or control costs.

PMID- 9644360
TI  - Minimally invasive cardiac valve surgery.
AB  - With the recent advancement and experience in minimally invasive coronary artery
      bypass surgery in selected patients, minimally invasive valve surgery using
      similar techniques is promising. Coupled with the movement in cardiac surgery to
      decrease costs, hospital lengths of stay and recovery time, minimally invasive
      techniques for both mitral and aortic valve surgery are promptly being pursued.
      This article reviews various minimally invasive surgical techniques for mitral
      and aortic valve surgery. Mitral valve surgery by means of port-access technology
      is detailed. Techniques for minimally invasive aortic valve surgery via a
      ministernotomy and a parasternal incision are described.

PMID- 9644361
TI  - Transmyocardial revascularization surgery.
AB  - Transmyocardial revascularization (TMR) surgery is a palliative and investigative
      surgical procedure with the goal of increasing the quality of life for patients
      with intractable angina pectoris who are unsuitable for percutaneous transluminal
      coronary angioplasty or coronary artery bypass graft surgery. It improves
      myocardial perfusion and oxygen supply to the left ventricle, thus decreasing the
      frequency and intensity of anginal episodes. Many patients continue to have
      episodes of angina post-operatively but the frequency of those episodes should
      decrease. TMR may be a good treatment option for otherwise untreatable patients
      who live with severe, debilitating angina.

PMID- 9644362
TI  - Perceived and unmet needs of critical care family members.
AB  - Family members of patients in the intensive care unit (ICU) may experience
      stress, disorganization, and helplessness which may ultimately result in
      difficulty in mobilizing appropriate coping resources, thus leading to anxiety.
      The needs of family members are varied, and critical care nurses must become
      attuned to these needs and acquire the skills to direct their interventions more
      appropriately. This article presents the findings from a study that assessed the
      perceived level of importance of the needs of family members during the first 18
      to 24 hours after admission to the ICU using the Critical care Family Needs
      Inventory. The study identified which needs were perceived as being met or unmet
      by the family members using the Needs Met Inventory after 36 to 48 hours had
      elapsed.

PMID- 9644363
TI  - Reducing costs and improving processes for the interventional cardiology patient.
AB  - The cardiology unit at the University of Chicago Hospitals developed a cost
      saving mechanism in the care of postinterventional cardiology patients, reducing
      time spent in the coronary care unit. Increased nursing education and training
      and better identification of patient outcomes made this collaborative effort a
      cost-saving and effective pilot.

PMID- 9644364
TI  - Aggressive implementation of advance directives.
AB  - Economic, social, and technical factors are an impetus for expressing end-of-life
      decisions as advance directives. Despite opportunities, nurses do not appear to
      be widely involved in practice and research regarding advance directives. Through
      an extensive literature review, this article will discuss a historical
      background, definitions of advance directives, positive outcomes, and several
      barriers to completion. Critical care nurses and advance practice nurses play a
      key role in educating nurses, their patients, and physicians about advance
      directives. The use of advance directives will likely increase if nurses can
      aggressively implement a plan on their unit. Specific methods of implementation
      are explored.

PMID- 9644365
TI  - Home care and the elderly.

PMID- 9644366
TI  - Autonomy and the cognitively impaired elder.

PMID- 9644367
TI  - Sleep disorders.
AB  - Many clients have trouble battling afternoon fatigue, falling asleep, staying
      asleep, or having a restful night's sleep. Approximately 33% of the adult U.S.
      population--about 65 million people--suffer from sleep disorders. One of two
      people have experienced insomnia. At least 10 million people have sleep apnea,
      hundreds of thousands have experienced narcolepsy, and approximately 12 million
      suffer from restless legs syndrome or periodic limb movements during sleep.
      However, most people with sleep disorders remain undiagnosed and untreated.

PMID- 9644368
TI  - Principles of disinfection.
AB  - For more than 150 years, we have known that medical and surgical devices may
      serve as vehicles for the transmission of infectious agents to a susceptible
      host. During that time, our knowledge and experience involving microbial
      inactivation through disinfection have become quite sophisticated. As a result,
      infectious complications associated with patient care are now the exception
      rather than the rule.

PMID- 9644369
TI  - Risk factors for drug-related problems in elderly ambulatory patients.
AB  - Medication use among elderly patients in ambulatory care, home health care, and
      long-term care settings has become increasingly complicated during the past
      decade. Home intravenous therapy, multiple drug regimens to treat multiple
      chronic diseases, increased acuity of nonhospitalized patients, and increased
      longevity have placed elderly patients at increased risk for drug-related
      problems.

PMID- 9644370
TI  - Home health industry feels impact of new Medicare changes.

PMID- 9644371
TI  - The most appropriate health care in the right place, and the right time. The
      importance of clinical decision support criteria in home health care.

PMID- 9644372
TI  - Evaluating support services to seniors. A discussion of collaborative research.
AB  - The difficulties involved in attempting to turn collaboration into partnership
      are revealed in this article about the relationship between research funders and
      researchers, specifically government funders and university researchers. Some
      discussion revolves around the relationships between researchers and among the
      researchers, practitioners, and consumers. This article also discusses
      collaborative research relationships by using the evaluation of a support program
      to seniors as an illustration. Also addressed are how the research revealed the
      success of the program and the frustrations encountered when government would not
      act on the findings.

PMID- 9644373
TI  - Diversity and aging. Cultural understanding as a powerful force in patient
      centered healing.
AB  - Culture describes a group whose members share common beliefs, values, traditions,
      symbols, language, and socialization styles. As an individual moves through the
      stages of life, he or she experiences a variety of cultures through membership in
      families, jobs, communities, and churches. Each culture contributes to the unique
      composition of a given individual. It comes as no surprise that elders older than
      60 present the most diversity of any age group. This article discusses that
      diversity and assumptions that challenge the health care provider working in the
      community.

PMID- 9644374
TI  - Exercise, immunity, acute respiratory infections, and homebound older adults.
AB  - Appropriate exercise may enhance immune function and lessen acute upper and lower
      respiratory tract infection (ULRI) symptoms in older adults. Home health care
      professionals need to know about this potential exercise effect because increased
      disease resistance and well-being can have a direct impact on activities of daily
      living (ADL) and independence. This article discusses recent exercise immunology
      research results, briefly explains the pathways by which exercise might affect
      immunity and ULRI, and provides guidance for home health care personnel regarding
      the delivery of an exercise program for their clients.

PMID- 9644375
TI  - American Subacute Care Association. Comparing OASIS, FIM, and MDS in assessing
      disability.

PMID- 9644376
TI  - How much is too much?

PMID- 9644377
TI  - Home healthcare nursing in the managed care environment. Part II. The impact on
      clients and professional nurses.
AB  - Part I, published in last month's issue of Home Healthcare Nurse, provided
      information about managed care and health maintenance organizations (HMOs). This
      article, Part II, presents an overview of the history of home healthcare nursing,
      the results of a purposeful sample, and interviews of home care nurses.
      Interviews were conducted to determine how nurses perceived the impact of managed
      care on their clients and nursing practice. Conclusions are presented in terms of
      emergent categories gleaned from the interviews. Recommendations for the
      continued growth and advancement of professional nursing in the context of
      managed care are given.

PMID- 9644378
TI  - Volunteers as members of the home healthcare and hospice teams.
AB  - A volunteer program has multiple advantages to the patients, their families,
      their nurses, the hospice, and the volunteers themselves (Harris, 1990). Home
      care volunteerism make good sense. If properly administered, it is cost-efficient
      and delivers a quality of care that can be acquired in no other way (Sodano,
      1997;764). Given the many changes that continue to take place in home healthcare
      and hospice regulations and financing, volunteers are a vital component of both
      programs so that patients and families continue to receive high-quality care.
      Volunteers are important members of the home healthcare and hospice teams.

PMID- 9644379
TI  - Postpartum home visits: extending the continuum of care from hospital to home.
AB  - Crucial maternal, newborn, and family healthcare needs arise during the early
      postpartum period, providing the opportunity for home care nurses to extend the
      continuum of care from hospital to home. This study identifies common early
      postpartum problems discovered on home health visits and describes the related
      interventions of home health nurses. Correlational analysis revealed that young
      mothers, first-time mothers, breastfeeding mothers, and single mothers are
      priority candidates for follow-up home care.

PMID- 9644380
TI  - Using community resources effectively to plan care.

PMID- 9644381
TI  - Developing collaborative multisite research in home care.
AB  - This article present the collaborative process for conducting research among a
      state home care foundation, its associated membership, and a university. Research
      collaboration allowed the merging of talents and resources from persons, home
      care agencies, and a university. The history and development of the project,
      sampling procedure, and data collection and analysis are discussed. The project
      increased the appreciation for research, allowed an opportunity for scholarly
      exchange, and accented the positive use of resources in all settings.

PMID- 9644382
TI  - Exaggerating the capability to provide care in the home: more than just
      "puffing"?

PMID- 9644383
TI  - Urinary tract infections in the homebound elderly.
AB  - The incidence of bacteriuria is widespread in the elderly. Because home care
      nurses serve elderly clients with multiple problems, bacteriuria is often
      encountered in the home care setting. The elderly may present with typical signs
      and symptoms of infection. However, the indications are often vague and
      nonspecific. Bacteria in the urine often presents with no symptoms and is best
      left untreated. The responsibilities of the nurse include evaluating signs and
      symptoms presented by their clients and overseeing therapeutic plans, specimen
      collection, infection control practices, catheter care, education, and
      prevention. It is important that prevention always receive top priority.

PMID- 9644384
TI  - Frequently asked questions about warfarin sodium.

PMID- 9644385
TI  - Preparing for the home health nurse certification examination.
AB  - Becoming certified in an area of nursing practice is one way of demonstrating
      expertise and competency in that area. Proper preparation is the key to
      successfully become certified. Study hints and test-taking strategies are
      discussed in detail. Specific information is provided on preparation to take the
      American Nurses Credentialing Center (ANCC) Generalist Home Health Nurse
      certification examination.

PMID- 9644386
TI  - Home care nursing: satisfaction.

PMID- 9644387
TI  - Ars Moriendi: illuminations on 'the good death' from the arts and humanities.

PMID- 9644388
TI  - Hospice: current practice, future possibilities.

PMID- 9644389
TI  - Managed, capitated care: opportunities for good and evil.

PMID- 9644390
TI  - Pain, symptoms, and suffering: possibilities and barriers.

PMID- 9644391
TI  - Visions and strategies: what participants and others might do.

PMID- 9644392
TI  - Demography and epidemiology of dying in the U.S. with emphasis on deaths of older
      persons.
AB  - As chronic disease continues to be the major cause of death and as the elderly
      population grows, it is important to evaluate the adequacy and completeness of
      health care strategies for the elderly. Two studies, the National Mortality
      Followback Survey and the National Institute on Aging Survey of the Last Days of
      Life, were designed to examine the circumstances of death for representative
      samples of decedents. Four areas of focus are location of death, transitions
      among health care settings, circumstances at the time of death, and changes in
      physical and cognitive function in the last year of life. Although the data are
      helpful for family planning, they are limited by a lack of data on costs.

PMID- 9644393
TI  - A history of the Medicare hospice benefit.
AB  - Since the inception of the Medicare hospice benefit, hospice has marked a new
      approach to managed care. Its focus on cost-effectiveness has made it one of
      Medicare's most successful managed care options. Various restrictions were placed
      on the hospice program; but, in return for these limitations, advocates of the
      program received an opportunity to create a program entirely different from other
      Medicare providers. The challenges of operating a hospice include electing
      hospice care, candid communication, and the relationship with other providers.
      These challenges will continue to burden hospices until discussions of death can
      be direct, clear, and knowledgeable.

PMID- 9644394
TI  - Predicting patient survival before and after hospice enrollment.
AB  - Despite the apparent advantages of hospice care, several barriers exist in terms
      of patient referral. Physicians' prognoses play a large role in determining when
      hospice care should begin. Predicting patient survival is a subjective decision
      dependent on several factors that vary before and after hospice enrollment.
      Currently, the stay of patients in hospice is very short; this can be attributed
      to late referral by physicians. Additional research on physician behavior and
      prognostication could help optimize the use of hospice as a valuable health care
      resource, thereby improving end of life care for terminally ill patients.

PMID- 9644395
TI  - Pain and the barriers to its relief at the end of life: a lesson for improving
      end of life health care.
AB  - Pain among cancer patients is a common distressing symptom that frequently
      affects physical functioning, social interaction, psychological status, and
      quality of life. Despite the extensive body of knowledge available regarding
      cancer pain assessment and management, it often remains untreated, thereby
      diminishing the quality of patient care at the end of life. Recommendations on
      how to remove these barriers, as well as to improve care of the dying in general,
      need to be implemented by the U.S. government.

PMID- 9644396
TI  - Why not the best for the chronically ill?
AB  - Premium adjustors to neutralize risk selection among health plans are the weakest
      component in the technology for assuring competitive markets. It will be many
      years before we have adjustors adequate to free health plans to invest in and
      market improved managed care to predictably high-cost chronically ill persons.
      For want of a fair premium, health plans are driven by risk selection to
      underinvest in and otherwise "demarket" care to these very employees and
      beneficiaries whose costs and care most need to be managed. To achieve best value
      for the chronically ill, large employer coalitions, Medicare, and Medicaid should
      consider radical new approaches, such as establishing separate prices for care to
      people with specific chronic conditions and purchasing such care both from health
      plans and directly from provider systems.

PMID- 9644397
TI  - The importance of measuring quality of care at the end of life.
AB  - Although designed to respond to acute illness, the current health care system
      must increasingly provide care for people living longer with chronic diseases.
      Evaluation of the quality of this care must utilize appropriate measurements,
      study populations, and outcomes. Current quality measures and major studies of
      quality of care are highlighted. A framework for measuring quality of care is
      outlined.

PMID- 9644398
TI  - An update on efforts by the hospice community and the National Hospice
      Organization to improve access to quality hospice care.
AB  - More than a year has passed since the Center to Improve Care of the Dying and the
      Corcoran Gallery of Art sponsored the symposium entitled: A Good Dying: Shaping
      Health Care for the Last Months of Life. Using the National Hospice Foundation
      sponsored exhibition, Hospice: A Photographic Inquiry, as a backdrop, the
      symposium included presentations on the current state of hospice care as well as
      the obstacles that limit access to hospice care. This article represents an
      update on many of the activities of the National Hospice Organization and the
      greater hospice community as we continue to improve access to quality hospice
      care.

PMID- 9644399
TI  - Overview on ABIM End-of-Life Patient Care Project: caring for the dying:
      identification and promotion of physician competency.
AB  - The American Board of Internal Medicine's project to improve end-of-life care was
      initiated in response to lack of attention given to death and dying in the United
      States. The project focuses mainly on physician competency in residency and
      fellowship training. With this data, recommendations can be made to improve
      physician training in end-of-life care treatment.

PMID- 9644400
TI  - Quality end of life care: the case for a MediCaring demonstration.
AB  - People in the last phase of life often need a very different care system than the
      one currently available. MediCaring extends the hospice model to a larger
      population with a wider array of services over a longer period of time with an
      emphasis on symptom management, maintenance of function, comfort and family
      counseling. This model requires simultaneous efforts to secure longer life and to
      make the patient and family ready for dying. Services range from psychological
      and spiritual counseling for the patient and family, to emergency care access, to
      inpatient respite care. MediCaring would accomplish these goals without
      increasing costs, primarily by diminishing the use of acute care interventions
      that may no longer serve the patient.

PMID- 9644401
TI  - New endeavors and innovative programs in end of life care.
AB  - This paper presents summaries of initiatives and demonstration programs developed
      by professional and patient care organizations to improve care at the end of
      life.

PMID- 9644402
TI  - Case management in a rural context.

PMID- 9644403
TI  - Managed care, health care reform, and the role of providers of aging services.
      Devolution threatens the safety-net role played by the federal government.
AB  - Managed care which emphasizes the rationalization of the way health care is
      financed, the devolution movement which shifts greater program responsibility to
      the state and local levels, and the restructuring of Medicaid along the lines of
      a block grant program, are issues presenting providers of aging services with a
      daunting set of challenges and opportunities. Providers of aging services will
      need to build on existing strengths, while developing new strategies, to succeed
      under an environment of managed care and state and local funding control.

PMID- 9644404
TI  - Barriers to providing case management to older rural persons.
AB  - This article analyzes data from a national sample of 356 agencies on barriers to
      providing case management to rural older persons. Although considerable variation
      is found regarding the degree of difficulty attributed to various barriers,
      several areas are reported by respondents as problematic, such as a lack of
      resources to pay for case management and services, a lack of services, and a lack
      of transportation. On the other hand, a lack of rural case management standards,
      qualified persons to conduct case management, and opportunities for staff
      training, as well as staff turnover and professional isolation, are generally not
      seen as particularly troublesome. More support from families and personal
      knowledge of clients and service providers are most likely to be seen as
      advantages in providing case management to rural elders. These findings both
      support and contradict the current gerontological literature on the types of
      barriers that impede the development and provision of services to rural older
      persons. Additional research is needed on the barriers to providing case
      management to rural older persons before policies directing scarce resources are
      put into place.

PMID- 9644405
TI  - Interactive televideo and the Internet in rural case management.
AB  - The purpose of this article is to stir the imagination and incite the creative
      energies of case managers in finding ways to capitalize on communication and
      information technologies to improve access to care as well as the quality of care
      in rural communities. Today, the general dearth of services and logistics of
      providing services in rural areas challenges even the most seasoned case
      managers. Given the current economic and political climate, it is unlikely that
      these challenges will lessen, particularly if we continue to pursue our more
      traditional approaches to case management and service delivery.
      Telecommunications technologies are opening exciting opportunities for changing
      this trajectory and expanding the role and reach of case managers, while
      improving access to many services. This article highlights the new and the
      potential applications of interactive televideo in health and human services, as
      well as the vast opportunities offered by the Internet. There are, however, also
      pitfalls we must overcome to realize the full potential of these technologies.
      Case managers, in their roles as advocates, coordinators, and facilitators, are
      ideally positioned to be on the cutting edge of these technological applications
      and play a catalytic role in moving rural communities into the "information age."

PMID- 9644406
TI  - Rural mental health and aging: implication for case management.
AB  - Older adults are underrepresented as recipients of mental health services,
      despite evidence that preventive interventions are effective and complement
      physical health interventions. Barriers to using these services include the
      stigma associated with mental health problems, lack of trained professionals and
      general barriers of availability and accessibility in rural service delivery.
      Case managers can play an important role in breaking down some of these barriers
      and assisting older adults to access t-ese services. Several outreach and
      educational models have been developed that are replicable and available to case
      managers.

PMID- 9644407
TI  - Formal home care services: examining the long-term care needs of rural older
      women.
AB  - Little data or current research exists regarding the specific long-term care
      needs of rural older women. This article examines the variables that appear to
      influence the availability of formal home care services. Utilization is discussed
      within the context of the specific social, cultural, and demographic factors that
      are applicable to this group of individuals. A description of the unique health
      care considerations of older women is also presented, along with recommendations
      for future research efforts and programming initiatives.

PMID- 9644408
TI  - Decision making by high functional status elders regarding nursing home
      placement.
AB  - An analysis of the Minimum Data Set Plus (MDS+) from one midwestern state
      revealed a group of "high functional elders" entering nursing homes, who
      potentially could be served in the community at a lower cost. The purpose of this
      qualitative study was to identify and better understand the reasons why these
      apparently high functioning elder adults entered nursing homes. Data from the
      1995 MDS+ were used to identify "high functional" elders recently admitted to the
      nursing home from two urban and seven rural counties. Data were collected through
      in-depth, face-to-face, semi-structured interviews and analyzed using qualitative
      content analysis. Of the 33 persons judged to be high functional, only 36%
      remained in the nursing home 3 to 6 months later. Most elders were using a wide
      array of community-based services and extensive informal support networks prior
      to entering the nursing home. Most described specific events that forced them
      into the nursing home environment. Health needs, specifically the need for 24
      hour care or supervision, emerged as the dominant factor for remaining in the
      nursing home. Of the 12 elders interviewed, all demonstrated some evidence of
      cognitive impairment. This study suggests that there are persons in nursing
      facilities today for whom community-based services, such as affordable assisted
      living, would be reasonable and appropriate. Case managers may be the most
      qualified not only to assess for and coordinate services, but also to advocate
      for affordable services that preserve elders' functional status.

PMID- 9644409
TI  - I want to live here for rest of my life. The challenge of case management for
      rural seniors.
AB  - The research on long-term care for seniors clearly demonstrates that efforts to
      integrate urban case management services with elderly people living in rural
      settings have not been successful. Presenting findings of the Rural Seniors
      Assisted Living Study conducted in northwestern Ontario, Canada, this article
      demonstrates the complexity of providing health and social services for seniors
      living in small rural communities, services that are often vastly different from
      those provided in urban communities. The article proposes a specialized Rural
      Case Management approach with rural elderly clients and identifies four
      intervention roles: providing direct service, consulting extensively with
      specialists of other disciplines, constructing and supporting natural helping
      networks, and resource management. The approach also requires that the rural case
      manager assume a leadership role at the community level in the development of
      services for seniors. Having a locally based case manager rather that a case
      manager who travels out to rural areas from an urban center is essential to the
      success of this rural case management approach. Finally, the article contends
      that rural case management differs from urban case management by requiring
      specialized knowledge, skills and educational programs.

PMID- 9644410
TI  - Outcomes associated with advanced nursing practice prescriptive authority.
AB  - Thirty-three advanced practice nurses (APNs) in 25 different primary care sites
      in one state participated in a study of the safety and effectiveness of APN
      prescriptive authority. Data were analyzed on 1,708 patients seen during a 2
      month period. Outcomes of care were studied using three different measures as
      well as patient satisfaction. Evaluation of patient outcome by APN and physician
      indicated that in 76% of the cases, the patient's condition stabilized or
      improved. Patients evaluated their own outcomes positively. Participating
      physicians were unanimous in their evaluation of APN prescriptive authority as
      beneficial to their patients.

PMID- 9644412
TI  - Cardiac information on the Internet.

PMID- 9644413
TI  - Vulvodynia: diagnosis and management.

PMID- 9644411
TI  - A preliminary study of the use of peer support in smoking cessation programs for
      pregnant adolescents.
AB  - This article describes preliminary findings of an experimental, randomized, three
      group, controlled design examining the effectiveness of a smoking cessation
      intervention for pregnant teens. The three groups are: Teen FreshStart with a
      buddy program (TFSB), a Teen FreshStart program (TFS) without peer support, and
      the Usual Care (UC) control group. Forty-six subjects completed the post
      intervention assessment of smoking status. The TFSB group consistently achieved
      greater smoking cessation across all measures when compared to the subjects in
      the other two groups. These results indicate that the use of peer support may be
      an effective adjunct in smoking cessation programs for pregnant adolescents.

PMID- 9644414
TI  - Pulmonary contusions: management and implications for trauma nurses.
AB  - TOPIC: Pathophysiology of pulmonary contusions, current methods for assessing
      blunt chest trauma patients, pulmonary parameters and diagnostic methodology, and
      innovative ventilatory treatment. PURPOSE: To heighten awareness of pulmonary
      contusion, the treatment and potential sequelae. SOURCES: Published information
      and clinical experience. CONCLUSION: A pulmonary contusion is a common
      potentially lethal chest injury seen in this country. Trauma clinicians should
      have heightened awareness about this injury because the injury is often
      overlooked and the clinicians frequently do not comprehend the mechanisms causing
      pulmonary contusions.

PMID- 9644415
TI  - Case study: trauma care in a nontrauma center.

PMID- 9644416
TI  - Trauma service quality assurance and improvement summary form.

PMID- 9644417
TI  - Supreme Court issues decisions in assisted suicide cases.

PMID- 9644418
TI  - From cacophony to symphony: healthcare needs a conductor.

PMID- 9644419
TI  - Clinical management protocols: the bedside answer to clinical practice
      guidelines.
AB  - TOPIC: Clinical Management Protocols for trauma patients. PURPOSE: The goals and
      process for developing and implementing Clinical Management Protocols are
      presented. Protocol development and the differences between clinical practice
      guidelines, critical pathways, and clinical management protocols are discussed.
      SOURCES: Published literature, experience, and clinical expertise. CONCLUSIONS:
      Utilizing annotated algorithms, the protocols are designed for and driven by
      patient care based on patient need and require the collaboration of experts and
      trauma team members.

PMID- 9644420
TI  - Trauma prevention: an evaluation tool for youth and alcohol trauma-prevention
      programs.
AB  - PURPOSE: To evaluate the Student Alcohol Questionnaire (SAQ) for use
      drinking/driving prevention programs in college-age students. METHODS: A pilot
      study of 39 students was conducted, which included a pre-test covering
      demographics and using the SAQ. A post-test was given as a program evaluation.
      The SAQ was repeated one month later. FINDINGS: At program completion, 40% of
      students stated that they would change behavior. The SAQ findings revealed no
      statistically significant changes in the pre- and post-tests. CONCLUSIONS: The
      SAQ may be an effective tool for measuring prevention programs.

PMID- 9644421
TI  - The top ten things to know and recognize when caring for adult victims of
      domestic violence.

PMID- 9644422
TI  - The Trauma Center Survival Questionnaire.

PMID- 9644423
TI  - Making education relevant to clinical practice.

PMID- 9644424
TI  - Wound management in staged abdominal repair.

PMID- 9644425
TI  - Measuring interface pressures in mattresses.
AB  - This evaluation compared the pressure support qualities of three mattresses by
      measuring the interface pressures using 20 subjects. The results indicate that
      the Pegasus Airwave mattress had significantly higher readings than Quattro
      DC2000 (p = 0.021, 95% confidence level) and the Nimbus II (p = 0.009, 99%
      confidence level) but that there is no significant difference between interface
      pressures for the Quattro DC2000 and the Nimbus II.

PMID- 9644426
TI  - Evaluating pressure-relieving mattresses.
AB  - In this study, three mattresses were evaluated to assess their effectiveness in
      relation to the pain and discomfort experienced by 40 patients with neurological
      disorders who had Waterlow scores > or = 15 and required pressure support. The
      results indicate that one mattress (the Quattro DC2000) performed significantly
      better than the other two (Nimbus II and Pegasus Airwave).

PMID- 9644427
TI  - An in vitro investigation of multi-layer bandages.
AB  - This study compares the elastic properties of a number of different bandages both
      in the non-sterile condition and after sterilisation by autoclaving at 134-138
      degrees C. Results suggest that, although some products can withstand
      sterilisation, the performance of some elasticated and coated bandages is
      adversely affected by excessive heat.

PMID- 9644428
TI  - The importance of secondary dressings in wound care.

PMID- 9644429
TI  - The fatal wounding of Emperor John II Comnenus.

PMID- 9644430
TI  - 1. Management practice at leg ulcer clinics. Patient examination and wound
      assessment.

PMID- 9644431
TI  - Management practice at leg ulcer clinics. 2. Challenges in diagnosis.

PMID- 9644432
TI  - Management practice at leg ulcer clinics. 3. Factors affecting healing.

PMID- 9644433
TI  - Lower limb amputation: planning surgery.

PMID- 9644434
TI  - Wound assessment methods.

PMID- 9644435
TI  - Epidemiological issues in monitoring pressure damage.

PMID- 9644436
TI  - Women's health care: roots to recommendations.

PMID- 9644437
TI  - Differential diagnosis of lower abdominal pain in women of childbearing age.

PMID- 9644438
TI  - Prescribing medication in pregnancy.
AB  - When prescribing medication in pregnancy, the clinician must follow some
      principles of prescribing. These include timing of exposure, dosage, duration of
      use, and fetal susceptibility. The health care provider must weigh the risk of
      exposure to the fetus with the benefit of treatment. This article summarizes the
      effect of selected medications used to treat common primary care disorders. These
      disorders include gastrointestinal complaints, asthma and allergies, infections,
      diabetes, epilepsy, headache, thyroid disorders, depression, and anxiety. The use
      and risks associated with common medications are discussed. Although no drug can
      be proven completely safe, prescribing medication with a long safety record,
      avoiding exposure in the first trimester, avoiding multidrug regimens, and
      prescribing the lowest dose for the shortest duration will minimize the fetal
      risk.

PMID- 9644439
TI  - Ovarian cancer screening: a primary care guide.
AB  - Ovarian cancer is a deadly disease, rarely diagnosed in early stages when the
      possibility for cure exists. A reliable screening technique would reduce the
      number of late-stage diagnoses and increase the long-term survival of ovarian
      cancer patients. Unfortunately, the absence of an identified premalignant phase
      of the disease makes it virtually impossible to develop an effective routine
      screening technique. This article reviews the risk factors related to the
      increased incidence of ovarian cancer. Advanced age and factors related to
      incessant ovulation, such as early menarche, late menopause, nulliparity, or few
      pregnancies, have been shown to increase a woman's chance of developing ovarian
      cancer. Also, a family history of endometrial, colon, breast, or ovarian cancers
      may increase the likelihood of developing the disease. The role of the primary
      care provider in the identification of high-risk individuals is reviewed, and
      currently available early detection test such as pelvic examination, CA-125,
      abdominal or pelvic ultrasound, and color-flow Doppler technique are summarized.

PMID- 9644440
TI  - Telephone triage in women's health care.
AB  - This article describes the importance of sound telephone triage strategies in
      women's health care. A brief description of the history of telephone triage is
      provided as well as basic considerations in establishing a telephone triage
      system. A sample telephone report sheet is also provided.

PMID- 9644441
TI  - Menopause: providing comprehensive care for women in transition.
AB  - Knowledge and research on the physiological changes associated with menopause is
      steadily expanding. A partnership between women and health care providers can
      contribute to the quality of women's life expectancy which is estimated to be
      79.1 years (United States Bureau of Census, 1993). Menopause is a normal
      phenomena of aging and women experiencing menopause must have access to
      comprehensive care, including a complete history, thorough physical exam, risk
      factor and age-appropriate screening, and patient education. Studies confirm
      women's lack of knowledge concerning menopause and the need for education on
      bodily changes and approaches to self-care during transition. Decline in the
      ovarian production of estrogen and the feedback effect of gondatropins leads to
      an increased follicle-stimulating hormone (FSH) of 40 mlU/mL. Vasomotor flushing,
      night sweats, vaginal dryness, shortening of the menstrual cycle with heavy flow
      progressing to longer cycles and scant flow and eventual cessation of menses for
      a period of 12 consecutive months confirms menopause. A program of screening and
      education for self-care can enhance women's quality of life.

PMID- 9644442
TI  - Breast cancer and gene testing: risk, rationale, and responsibilities of primary
      care providers.
AB  - Family history is one of the known risk factors for breast cancer. Breast cancer
      susceptibility genes, BRCA-1 and BRCA-2, have been identified as accountable for
      less than 10% of all cases of breast cancer. Certain populations however,
      including native Icelanders and Ashkenazi Jews have a higher incidence of BRCA
      mutations than the general population. Genetic testing for these mutations is now
      available. Many ethical issues remain regarding who should be tested and what
      interventions should be carried out with positive test results. This article
      describes the patient assessment and counseling process for breast cancer testing
      to improve the knowledge base and confidence of the primary care provider.

PMID- 9644443
TI  - Shortened lengths of stay: ensuring continuity of care for mothers and babies.
AB  - Hospital discharge on the day after an uncomplicated vaginal delivery may be
      appropriate if clinical criteria are used for the selection of patients and post
      discharge follow-up plans are in place. To ensure safety for these patients,
      Advocate Health Care developed a mother/baby philosophy statement, guidelines for
      maternal and infant discharge in less than 48 hours, and an algorithm to assure
      that appropriate follow-up care takes place after discharge. To evaluate the
      Mother/Baby Home Transition Program, home health follow up, readmission rates,
      and sentinel events were tracked. Most home health visits occurred within 48
      hours. Infant readmission rates ranged from 1.1-2.6%, whereas maternal
      readmission rates ranged from 0-0.52%. Three sentinel events in 1996 and three in
      1997 required readmissions to an ICU. Data continue to be monitored and shared
      monthly with clinical leaders.

PMID- 9644444
TI  - "Natural" hormone replacement therapy and dietary supplements used in the
      treatment of menopausal symptoms.

PMID- 9644445
TI  - Herpes genitalis.

PMID- 9644447
TI  - Preventing and recognizing STDs.

PMID- 9644446
TI  - Pelvic inflammatory disease.

PMID- 9644448
TI  - Understanding the abnormal Pap smear.

PMID- 9644449
TI  - Preparing for colposcopy.

PMID- 9644450
TI  - Unraveling the mystery of chronic amenorrhea.

PMID- 9644451
TI  - Hepatitis in the ESRD setting: defining the risks.
AB  - Although hepatitis can be a significant problem for dialysis patients and staff,
      the risk of contracting hepatitis can be reduced. Next month, part two will
      address preventive strategies that may be utilized to reduce the risk of
      transmission of hepatitis between patients and staff.

PMID- 9644452
TI  - After 10 years, the OPTN regulations arrive--what's next?

PMID- 9644453
TI  - Improving communication between patients and staff.

PMID- 9644454
TI  - Mediation: one method of resolving patient/staff differences.

PMID- 9644455
TI  - Monitoring quality of care.

PMID- 9644456
TI  - Patients' rights and responsibilities: a physician's view.

PMID- 9644457
TI  - Bringing advanced technologies of the Internet into the dialysis unit.

PMID- 9644458
TI  - Renal transplantation in Canada.

PMID- 9644459
TI  - DOQI guidelines and the vascular access puzzle: finding the pieces that fit.

PMID- 9644460
TI  - Specialist practice: the transitional arrangements.

PMID- 9644461
TI  - The minute paper: a quick guide to assessing student learning.

PMID- 9644462
TI  - Learning from the experiences of mental health nurses.

PMID- 9644463
TI  - The psychology of health promotion.

PMID- 9644464
TI  - Making sense of data.

PMID- 9644465
TI  - Becoming a manager and making a difference to patient care.

PMID- 9644466
TI  - Keep bad news about NHS out of the press.

PMID- 9644467
TI  - Working with nursing agencies.

PMID- 9644468
TI  - Strategic management for elderly care.

PMID- 9644469
TI  - An initiative in mental health nursing.

PMID- 9644470
TI  - Staff attitudes to clinical placements.

PMID- 9644471
TI  - Education for the future.

PMID- 9644472
TI  - Wilma McPherson -- the interview. Interview by Tom Keighley.

PMID- 9644473
TI  - Providing effective clinical supervision.

PMID- 9644474
TI  - Promoting change through peer review.

PMID- 9644475
TI  - The lobbying power of nurses.

PMID- 9644476
TI  - Relationships among HIV risk beliefs, attitudes, and behaviors in sexually
      active, seronegative gay men.
AB  - Safer-sex guidelines established during the early days of the HIV/AIDS epidemic
      have undergone very little revision despite some controversy. Although these
      guidelines have been widely disseminated in the gay community, many gay men
      continue to engage in behaviors that are believed to put them at high risk for
      transmission of HIV. This suggests either that they have not accepted safer-sex
      guidelines as accurate or that other factors override personal implementation of
      the guidelines. The study examined seronegative gay men's beliefs about the
      accuracy of safer sex guidelines and the men's participation in behaviors risky
      for transmitting HIV. The greatest disagreement between the men's beliefs and
      behaviors centered on the risk of oral intercourse; this suggests a need for
      clarification of the safer sex message about this behavior. The findings of this
      study support the need to reformulate safer-sex guidelines. When unprotected oral
      and anal sex are classified at the same level of risk, those who engage in
      unprotected oral sex may proceed to unprotected anal sex with less reservation.

PMID- 9644477
TI  - Does mandating continuing education mandate competence?

PMID- 9644478
TI  - Nursing education accepts new challenges.
AB  - This paper describes an innovative experience in which nursing students made home
      visits to postoperative patients. It was planned in cooperation with surgeons and
      nurses in the outpatient surgery department. Objectives for this experience were
      defined and students evaluated the effectiveness of their preoperative teaching
      and monitored the patients for potential complications.

PMID- 9644479
TI  - Advocacy and allocation.

PMID- 9644480
TI  - Role-modeling experience improves nursing students' attitudes toward people
      living with AIDS.
AB  - Two groups of student nurses were given on AIDS Knowledge/Attitudes survey before
      different clinical experiences. Group One worked with nurses experienced in the
      care of persons living with AIDS (PLWA) on a high-acuity unit with many AIDS
      patients. The other group were precepted on a acute-care unit with no AIDS
      patients. Outcomes measures revealed significantly better student attitude scores
      for Group One on scales measuring (1) avoidance intentions to working with PLWA
      and (2) attitude toward homosexuals.

PMID- 9644481
TI  - Multistate licensure: to support or not to support.

PMID- 9644482
TI  - Self-efficacy: an essential component of advanced-practice nursing.
AB  - The concept of self-efficacy has been used widely as a model for examining health
      promoting education in such areas as cardiac rehabilitation, smoking cessation,
      dietary modifications, pulmonary rehabilitation, and compliance with prescribed
      regimens. Consequently, self-efficacy has emerged as an essential concept in
      developing and implementing health promotion programs in advanced practice. Self
      efficacy refers to an individual's perceived ability to perform a specific
      behavior. It is the mediator between knowledge and action, and it influences the
      selection of behavior, the environment in which the behavior occurs, and the
      amount of effort and perseverance expended on performing the behavior. This paper
      analyzes the concept of self-efficacy and suggests applications of self-efficacy
      in advanced-practice nursing.

PMID- 9644484
TI  - Taking care with language.

PMID- 9644483
TI  - The effectiveness of guided design on ethical decision making and moral reasoning
      among community nursing students.
AB  - This study evaluated the effectiveness of guided design as an instructional
      method in ethical decision making and moral reasoning among 145 community health
      nursing students. Changes in the process of ethical decision making and moral
      reasoning were measured using Ketefian's judgment About Nursing Decisions (JAND)
      one week after the intervention. Results indicated a significant difference in
      ethical decision-making scores after instruction, but no difference in moral
      reasoning. The one specific component--Taking professional initiatives--increased
      on both subscales.

PMID- 9644485
TI  - Canadian contrasts.

PMID- 9644486
TI  - Reflections on the process of play interaction.

PMID- 9644487
TI  - Practical pathways: a multidisciplinary approach to asthma.

PMID- 9644488
TI  - Prolonged contact with topical anaesthetic cream: a case report.

PMID- 9644489
TI  - Psychological stress in critical care.

PMID- 9644490
TI  - 'How d'you know it's me'?

PMID- 9644491
TI  - Childhood diabetes: dietary aspects.

PMID- 9644492
TI  - Old habits. Will you pay for your past as a smokers?

PMID- 9644493
TI  - Impotence. Putting the pill (for men) in perspective.

PMID- 9644494
TI  - My doctor told me I tend to get dehydrated. Can I substitute other liquids for
      water?

PMID- 9644495
TI  - Temporal arteritis. A serious, mysterious headache.

PMID- 9644497
TI  - Folic acid and diet.

PMID- 9644496
TI  - Herbal insurance. Does an allium a day keep the doctor away?

PMID- 9644498
TI  - Exercise prevents gallstones.

PMID- 9644499
TI  - Sildenafil (Viagra): the new pill for impotence.

PMID- 9644500
TI  - Walking to health.

PMID- 9644501
TI  - The crucial, controversial carotid artery. Part II: Treatment.

PMID- 9644502
TI  - Prostate cancer: a new clue.

PMID- 9644503
TI  - My question, our 12-year-old son. Almost every time he eats ice cream he gets a
      terrible headache. I don't think he is allergic to milk, since he drinks it by
      the quart. What's wrong?

PMID- 9644504
TI  - The trauma of serious illness.

PMID- 9644505
TI  - Do you need cholesterol-lowering drugs?

PMID- 9644506
TI  - A new alternative to estrogen: raloxifene.

PMID- 9644507
TI  - Senior drivers.

PMID- 9644508
TI  - Prostate cancer test becomes more accurate.

PMID- 9644509
TI  - Allergic shock reaction.

PMID- 9644510
TI  - Calming ulcerative colitis.

PMID- 9644511
TI  - Exercise improves swallowing.

PMID- 9644512
TI  - Pain killers and diverticulitis.

PMID- 9644513
TI  - Are multiple health problems undertreated?

PMID- 9644514
TI  - Lyme disease vaccine.

PMID- 9644515
TI  - [Scientific heritage of Z.V. Ermol'eva and present].

PMID- 9644516
TI  - [On the history of penicillin preparation by Z.V. Ermol'eva].

PMID- 9644517
TI  - [Z.V.Ermol'eva: cholera control and prevention--her life commitment].

PMID- 9644518
TI  - [Contribution of Z.V.Ermol'eva to the research in the field of highly dangerous
      infections].

PMID- 9644519
TI  - [Studies of Z.V.Ermol'eva and her school in the field of isolation and
      characterization of lysozyme].

PMID- 9644520
TI  - [Biologically active compounds and scientific heritage of Z.V.Ermol'eva].

PMID- 9644521
TI  - [Interferons in cascade of cytokines: historic and modern aspects].

PMID- 9644522
TI  - [Studies of Z.V.Ermol'eva on antitumor effect of biologically active substances
      of animal origin].

PMID- 9644523
TI  - [Combined antibiotic therapy--one of the ways of increasing antibiotic efficacy].

PMID- 9644524
TI  - [Z.V.Ermol'eva--scientist and teacher].

PMID- 9644525
TI  - [Amoxycillin/clavulanic acid--beginning of new era in antibiotic therapy of
      bacterial infections].

PMID- 9644526
TI  - [Antibiotics: new mechanisms of resistance transfer].

PMID- 9644527
TI  - [Stepwise therapy of community-acquired pneumonia. Results of cefuroxime and
      cefuroxime axetil study].
AB  - The efficacy of a 7-day switch therapy with parenteral cefuroxime in a dose of
      750 mg for 3-5 days followed by the use of oral cefuroxime axetil in a dose of
      500 mg every 12 hours was compared with that of a 7-day therapy with parenteral
      cefuroxime in a dose of 750 mg every 8 hours in hospitalized patients with
      community-acquired pneumonia. The clinical and bacteriological efficacies and
      pharmacokinetic properties of both the dosage forms were estimated. It was shown
      that the clinical and bacteriological effects did not significantly differ in the
      patients under the parenteral regimen with cefuroxime and under the parenteral-to
      oral regimen with cefuroxime and cefuroxime axetil: the cure in 75 and 83 per
      cent of the patients and the bacteriological response in 100 and 86 per cent of
      the cases respectively. The results indicated that the cost of the switch therapy
      was much lower while the efficacy did not decrease.

PMID- 9644528
TI  - [Ceftriaxone in the treatment of staphylococcal endocarditis].
AB  - Efficacy and safety of ceftriaxone (Oframax, Ranbaxy, India) in the treatment of
      25 patients with Staphylococcus endocarditis (SE) were studied. The drug was
      administered intravenously in a dose of 2-4 g a day for 4 weeks and
      simultaneously gentamicin was used intramuscularly in a dose of 2-3 mg/kg body
      weight a day every 8 hours for 2 weeks. The treatment was followed by observation
      of the patients for up to 2 years under the hospital or dyspensary conditions.
      The disease was due to S. epidermidis (17 patients) or S.aureus (8 patients). The
      efficacy was controlled in the dynamics. The criteria of the therapy efficacy
      were disappearance of the disease clinical signs, normalization of the blood
      count and urinalysis and the pathogen eradication by the results of the control
      bacteriological blood analysis. The cure without any surgical correction was
      observed in 68 per cent of the patients and that with the valve replacement was
      stated in 24 per cent of the patients. The lethal outcome due to bacteriotoxic
      shock was recorded in 8 per cent of the patients. The SE relapsing was stated in
      28 per cent of the patients 3 or more months after the ceftriaxone therapy
      completion. 10 patients (40 per cent) with evident clinicolaboratory improvement
      were discharged from the hospital 2 (4 patients) and 3 (6 patients) weeks after
      the therapy start for the treatment with ceftriaxone as outpatients. In 2
      patients nausea as the adverse reaction was observed. Therefore, the complex
      clinicolaboratory investigation showed that the combined use of ceftriaxone and
      gentamicin was efficient and safe in the treatment of SE. Ceftriaxone may be
      considered as a basic drug for the therapy of SE. In some patients with SE the
      treatment with ceftriaxone may be completed under outpatient conditions.

PMID- 9644529
TI  - [Clinical and laboratory study of cefodizime (Modivid) in prophylaxis and
      treatment of surgical patients].
AB  - The results of the clinical and laboratory study of the efficacy of the
      prophylactic and therapeutic use of cefodizime (modivid) in patients with chronic
      calculous cholecystitis and burns are presented. Expediency of the preoperative
      prophylactic use of the drug and its significance in the treatment of infectious
      complications of the burn disease were verified. The immunological investigation
      gave evidence of an increase of the phagocytosis functional activity when
      cefodizime (modivid) was used prophylactically in cholecystectomy.

PMID- 9644530
TI  - [Isolation and identification of Mycobacterium cultures antagonistic to
      phytopathogenic microflora].
AB  - A number of saprophytic bacteria were isolated from natural substrates. Their
      identification showed that the majority of the isolates belonged to the genus
      Mycobacterium. The previously developed test-system including treatment of soil
      substrates by alkali and the use of optimal nutrient media provided preferencial
      isolation of saprophytic mycobacteria. The primary studies demonstrated that the
      cultures belonging to the genus Mycobacterium had antifungal properties and might
      be promising for screening antagonists of phytopathogens.

PMID- 9644531
TI  - [Differential use of cephalosporins in treatment of upper and lower respiratory
      tract infections].

PMID- 9644532
TI  - [Methicillin resistant staphylococci].

PMID- 9644533
TI  - [Mechanisms of macrolide resistance in organisms producing them and in
      eubacteria].

PMID- 9644534
TI  - [In the commission on antibiotic policy].

PMID- 9644535
TI  - Regenerated hair cells become functional during continuous administration of
      kanamycin.
AB  - The compound action potential (CAP) was used to assess the functional status of
      regenerated hair cells in the chick cochlea during prolonged administration of
      kanamycin (KM). Immediately after 10 days of KM treatment, the CAP thresholds
      were elevated by 6-54 dB above those from age-matched control animals. The
      frequencies with the greatest threshold shifts (> 1 kHz) corresponded to the hair
      cell lesion in the basal 40% of the basilar papilla. After 20 days of KM, the CAP
      thresholds at 3 and 4 kHz were significantly lower than those after 10 days of KM
      treatment, but virtually the same as those after 10 days of KM plus 10 days of
      recovery. Similarly, the CAP amplitudes at frequencies higher than 1.5 kHz were
      significantly greater in animals that received KM for 20 days than in animals
      that received KM for 10 days. The threshold as well as amplitude improvement
      between 10 days and 20 days of KM treatment was associated with the morphological
      maturation of the regenerated hair cells in the basal 25% of the cochlea. In
      addition, the rapid functional recovery seen at high frequencies coincided with
      the base-to-apex gradient of morphological recovery in the basilar papilla. These
      results suggest that the process of hair cell maturation is not suppressed by the
      presence of aminoglycosides in the extracellular environment.

PMID- 9644536
TI  - Psychopathological profile of tinnitus sufferers: evidence concerning the
      relationship between tinnitus features and impact on life.
AB  - This study involving 281 French tinnitus sufferers sought to investigate possible
      correlations between psychopathological profile and scores obtained from three
      tinnitus questionnaires. The patients all completed a French version of the Mini
      Mult--a shortened Minnesota Multiphasic Personality Inventory--and French
      translations of three questionnaires designed especially for the clinical
      assessment of tinnitus: Tinnitus Reaction Questionnaire (TRQ), Subjective
      Tinnitus Severity Scale (STSS) and Tinnitus Handicap Questionnaire (THQ).
      Significant correlations were found (p < 0.0001) between scores on various Mini
      Mult scales and total or factor 1 THQ and total TRQ scores. No significant
      correlation was found between the STSS and any Mini-Mult score.

PMID- 9644537
TI  - A 'neural' response with 3-ms latency evoked by loud sound in profoundly deaf
      patients.
AB  - A large negative deflection with a latency of 3 ms was observed in the auditory
      brainstem response (ABR) waveforms of some patients with peripheral profound
      deafness. This deflection was termed the N3 potential. In this paper, we review
      patients with the N3 potential and discuss the characteristics of abnormal ABR
      waveforms. The origin of the N3 potential was also discussed, especially with
      respect to vestibular evoked potentials. In most of the patients, audiograms
      showed no response to the maximum output of an audiometer in the high-frequency
      range and a residual response in the low-frequency range. The N3 potentials were
      noted at intensities of 80 dB nHL or greater. As the stimulus intensity
      increased, the amplitude of the potential increased and the latency decreased. A
      high repetition rate (83.3/s) of the click stimulus influenced the latency and
      amplitude of the N3 potential. The potential was replicated on retest within less
      than a month, and had a consistent latency and amplitude over the scalp. The
      results indicate that the N3 potential is not an electrical artifact but a
      physiological neural response evoked by a loud sound. The N3 potential is most
      likely not an auditory evoked response from cochlear or a response from a
      semicircular canal, because it has a 3-ms latency, a sharp waveform, and is
      unassociated with vertigo. The results suggest that the N3 potential may be a
      saccular acoustic response.

PMID- 9644538
TI  - Three-dimensional reconstruction of the auditory cortical areas from magnetic
      resonance images.
AB  - The future of neuromagnetic research will be highly dependent on the development
      of analysis procedures utilizing morphological information derived from magnetic
      resonance (MR) images. However, constraining the biomagnetic inverse problem by
      using such information may lead to serious misinterpretations if the
      reconstruction algorithm for the cortical surface overlooks boundaries between
      grey matter and cerebrospinal fluid (CSF) or artificially generates them. The
      purpose of this study was to check as to what extent an advanced automatic three
      dimensional reconstruction procedure is able to segment the cortical structures
      located hidden in the Sylvian fissure (especially Heschl's gyrus and planum
      temporale). The procedure consisted of four processes: a coarse segmentation, a
      refined segmentation of the white matter, a skeletonization of the sulci and a
      segmentation of the cortical surface by concurrent region growing for brain and
      CSF. The reconstruction result for single slices basically agrees with the
      impression obtained upon visual inspection of the original MR data.
      Photorealistic visualizations, showing a good qualitative agreement with
      anatomical images, suggest that the reconstructed surfaces are realistic and
      detailed enough to be applicable in source analyses of auditory evoked fields.

PMID- 9644539
TI  - [Perftoran--blood substitute with oxygen transport function].

PMID- 9644540
TI  - [Resistance and capacitance of sural veins during electrical stimulation of
      ventral regions of the medulla oblongata].

PMID- 9644541
TI  - [Effect of simple proline-containing peptides on the functional activity of the
      anticoagulant system and primary homeostasis].

PMID- 9644542
TI  - [Peptide correction of disturbed relations in the central nervous system].

PMID- 9644543
TI  - [The role of endogenous neuromodulator peptides in enhancement of the functional
      tolerance of brain neurons to anoxia].

PMID- 9644544
TI  - [Effect of human apolipoprotein A-I gene on vasoactive properties of high density
      lipoproteins in rats of different age].

PMID- 9644545
TI  - [The role of Thy 1.2(+)-cells in regulation of hematopoiesis during cytostatic
      depression].

PMID- 9644546
TI  - [Characteristics of peptide vagotropic effects during subtotal blockade of heart
      M-cholinoreceptors].

PMID- 9644547
TI  - [Effect of lamotrigine on development of neurogenic pain syndrome in rats].

PMID- 9644548
TI  - [Comparative characteristics of cholinergic systems of the neocortex and
      hippocampus of rats with low and high resistance to hypoxia].

PMID- 9644549
TI  - [Effect of the intraperitoneal administration of spermine on oxidative processes
      in isolated liver mitochondria of rats during hypothermia].

PMID- 9644550
TI  - [Participation of oxygen free radicals in disturbance of restoration of the
      aerobic metabolism of the transplanted heart with different periods of
      conservation].

PMID- 9644551
TI  - [Interaction of 16alpha,17alpha-cyclopropanoprogesterone with progesterone
      receptor of the rat uterus].

PMID- 9644552
TI  - [Contribution of genetic and individually acquired factors in morphine
      sensitivity in WAG/G and Fischer-344 rats].

PMID- 9644554
TI  - [Potentiation of the efficacy of anticonvulsant diazepam by electrostimulation of
      the cerebellar cortex].

PMID- 9644553
TI  - [Effect of calcium channel blocker nifedipine on anxiety and seizure
      manifestations of abstinence syndrome in rats after withdrawal of long-term
      diazepam administration].

PMID- 9644555
TI  - [Anti-arrhythmia activity of befol, sufan, mexidol, and T3-146 in combination
      with other anti-arrhythmia agents].

PMID- 9644556
TI  - [Changes in parameters of nonspecific resistance of the body, humoral and
      cellular immunity after acute acetonitrile intoxication].

PMID- 9644557
TI  - [Characteristics of effects of mu-, delta-, and kappa-opioid agonists and
      enkephalinase inhibitor RB101 in rats of two inbred strains].

PMID- 9644558
TI  - [Differences in the composition of cellular elements of blood and lymphocyte
      dehydrogenase activity in rats with genetic variability in neuroendocrine
      status].

PMID- 9644559
TI  - [Determination of steroid hormone receptors in different tissues and neoplasms].

PMID- 9644560
TI  - [The role of glutathione and glutathione-S-transferase in neoplasm drug
      resistance].

PMID- 9644561
TI  - [Anticarcinogenic effect of palustran on development of tumors induced by 3-(1
      alpha-L-arabinopyranosyl)-1-methyl-1-nitrosourea (AMNU) in rats].

PMID- 9644562
TI  - [Effect of micronized fenofibrate (lipantyl-200M) on synthesis of cholesterol in
      peripheral blood lymphocytes of patients with ischemic heart disease and
      hyperlipidemia].

PMID- 9644563
TI  - [The level of sex steroid receptors in the myometrium during cesarean section].

PMID- 9644564
TI  - [Circadian and seasonal variations of the activity of blood lymphocyte
      dehydrogenases during secondary immunodeficiency in women with acute inflammatory
      gynecologic diseases of nonspecific etiology].

PMID- 9644565
TI  - [Production of cultured human placental macrophages].

PMID- 9644566
TI  - [Ultrastructure and proliferation of stomach epitheliocytes during ultraviolet
      laser irradiation].

PMID- 9644567
TI  - [Macrophages of the subcutaneous connective tissue during alpha-tocopherol
      administration and dehydration].

PMID- 9644568
TI  - [Effect of dextran infusions on destructive processes in the liver parenchyma
      during long-term crush syndrome].

PMID- 9644569
TI  - [Determination of antigens of anti-thrombocyte antibodies in patients with
      different forms of thrombocytopenia].

PMID- 9644570
TI  - A system for postoperative visualization and analysis of left ventricular
      pressure-volume loops.
AB  - A patient monitoring system for continuous real-time monitoring of left
      ventricular (LV) function in the postoperative setting was developed. Common
      hemodynamic parameters and LV functional indices are all calculated from left
      ventricular pressure-volume loops (PV-loops). Visualization of the PV-loops,
      along with the hemodynamic parameter derived from them, provides valuable insight
      into ventricular function and patient recovery. The pressure component is
      obtained via a pressure sensing catheter placed during surgery. Volume is
      measured via non-imaging radionuclide techniques using a modified Capintec-VEST.
      Following surgery and transfer to the recovery unit, the patient's blood is
      labeled with Tc-99m. A portable gamma camera is used to measure baseline ejection
      fraction (EF) and to aid in placing the VEST. The specific radioactivity of the
      blood is calibrated using the baseline EF and thermodilution cardiac output. To
      confirm the volume measurement accuracy of this technique six patients undergoing
      bilateral heart catheterization were studied. Single-plane cineventriculographic
      LV volumes were compared to those calculated from the VEST's time activity curve.

PMID- 9644571
TI  - Performance evaluation of filtered backprojection reconstruction and iterative
      reconstruction methods for PET images.
AB  - The filtered backprojection (FBP) algorithm and statistical model based iterative
      algorithms such as the maximum likelihood (ML) reconstruction or the maximum a
      posteriori (MAP) reconstruction are the two major classes of tomographic
      reconstruction methods. The FBP method is widely used in clinical setting while
      iterative methods have attracted research interests in the past decade. In this
      paper we studied the performance of the FBP, the ML and the MAP methods using
      simulated projection data. The experiment showed that the MAP algorithm generated
      superior image quality in terms of the bias, the variance, and the average mean
      squared error (MSE) measures.

PMID- 9644572
TI  - Regional cerebral blood flow determination using 133Xe and a standard rotating
      gamma-camera.
AB  - While most of the methods for quantitative regional cerebral blood flow (rCBF)
      determination in man requires expensive fast devices, a method is proposed using
      single photon emission computed tomography with a conventional rotating gamma
      camera and 133Xe inhalation. It is tested using a computer simulation of a
      cerebral exam and a simplified CBF map as a model. The results obtained show that
      this method is relevant and can be tested in clinical studies.

PMID- 9644573
TI  - A cluster computer system for the analysis and classification of massively large
      biomedical image data.
AB  - The current trend in medical image acquisition is towards the generation of image
      datasets which are massively large, either because they exhibit fine x, y, or z
      resolution, are volumetric, are multispectral, or a combination of all of the
      preceding. Such images pose a significant computational challenge in their
      analysis, not only in terms of data throughput, but also in terms of platform
      costs and simplicity. In this paper we describe the role of a cluster of
      workstations together with two quite different application programming interfaces
      (APIs) in the quantitative analysis of anatomic image data from the visible human
      project using an MRF-Gibbs classification algorithm. We describe the typical
      architecture of a cluster computer, two API options and the parallelization of
      the MRF-Gibbs procedure for the cluster. Finally, we show speedup results
      obtained on the cluster and sample classifications of visible human data.

PMID- 9644574
TI  - Detection of negative allosteric effects between monoclonal antibodies by using
      an antigenic model-builder computer program.
AB  - The ability of monoclonal antibodies (MAb) to bind or not simultaneously to the
      antigen (Ag) is used to establish antigenic maps considering that two different
      MAb do not bind to the Ag when the corresponding epitopes are overlapped (steric
      effect). Nevertheless, MAb inducing negative allosteric effect on the Ag could
      prevent the binding of the second MAb even if it is directed to a separate
      epitope. We report here that a knowledge-based expert module included in our
      previously described antigenic model-builder program (MAPAG) was able to
      differentiate between steric and negative allosteric effects between some MAb.

PMID- 9644575
TI  - An algorithm for the automatic differentiation between the speech of normals and
      patients with Friedreich's ataxia based on the short-time fractal dimension.
AB  - In this paper, we describe an algorithm, based on acoustic pattern matching
      techniques, for providing an automatic, highly reliable distinction between
      normal and some kind of pathological speech (Friedreich's ataxia disease). For
      each utterance, the short-time fractal dimension parameter and, for comparison,
      the zero-crossing and energy ratio parameters are evaluated and used in the
      classification task by means of a dynamic programming procedure. Although all the
      parameters are able to differentiate the two groups, the fractal dimension
      parameter seems to provide a more reliable pattern classification than zero
      crossing and energy ratio. Finally, we point out that, to the discrimination
      purpose, an accurate choice of the utterances to be pronounced by the subjects is
      to be considered.

PMID- 9644576
TI  - [Possible modeling of neural networks in the framework of thermodynamics of
      genetically disordered systems (glasses)].

PMID- 9644578
TI  - [Immediate and long-term functional and morphological changes in the neuronal
      structures of cerebral cortex of cats subjected to callosotomy].

PMID- 9644577
TI  - [Interchangeability of growth factors in early G(0)-G(1) period of cell cycle].

PMID- 9644579
TI  - [Nonmonotonous changes in erythrocyte sedimentation rate in whole blood].

PMID- 9644580
TI  - [Conformation aspects of stereospecificity of acetylcholinesterase hydrolysis of
      beta-methylcholine substrates].

PMID- 9644581
TI  - [Cytogenetic changes in thymus and bone marrow cells after exposure to pulsed
      infrared laser irradiation of locally irradiated mechanically damaged skeletal
      muscle of rats].

PMID- 9644582
TI  - [Response of rat skeletal muscle fibers and neuromuscular junction on strength
      exercise training].

PMID- 9644583
TI  - [Structural state of cell membranes in animal brain during development of
      hyperbaric hyperkinesias].

PMID- 9644584
TI  - [Topography and resolution of the retina in the dolphin Sotalia fluviatilus].

PMID- 9644585
TI  - [Karyotype of siberian roe-deer (Capreolus pygargus Pall.) from the northern
      border of the areal].

PMID- 9644586
TI  - [Phylogenetic analysis of ORF1-containing mobile elements: identification of
      evolutionary related groups].

PMID- 9644587
TI  - [Alkaline phosphatase in the Drosophila melanogaster strain characterized by
      differences in sexual behavior of males in normal and stressful conditions].

PMID- 9644588
TI  - [Radioadaptive response and antimutagenic effect of interferon have common
      pathways of cell protection against gamma radiation].

PMID- 9644589
TI  - [Increased frequency of recombination exchanges controlled by RecA protein from
      Pseudomonas aeruginosa].

PMID- 9644590
TI  - Hydrodynamic properties of gelatin in dilute solutions.
AB  - Aggregation properties of Gelatin chains in neutral aqueous solutions, are
      reported in the temperature range T = 35-60 degrees C, from the measured
      intrinsic viscosity [eta], diffusion coefficient, D(o), molecular weight Mw, and
      radius of gyration (Rg) data. Gelatin chains doubled their size as the solution
      was cooled to 35 degrees C from 60 degrees C. The intermolecular interaction was
      found to be repulsive which showed significant decrease as the temperature was
      reduced. The data provides excellent fitting to the scaling relations Mw[eta] =
      (1.96 +/- 0.06) x 10(-26)(Re,eta/Re,D)3(D(o) eta o/T)-3 and (D(o)n1/2)-1
      approximately equal to (6 1/2 pie eta o chi beta/kB/T)[1 + 0.201(v/beta 3)n1/2]
      where n is the number of segments in the chain. The ratio of the hydrodynamic
      radius (Re,D) (deduced from D(o)) and Rg, (Re,D/Rg = zeta) was found to be 0.555.
      From the known solvent viscosity eta o, the segment length beta, was deduced to
      be (15 +/- 2) A. The deduced excluded volume was v approximately equal to (4.1
      A)3. The Flory-Huggins interaction parameter (zeta) did not show observable
      temperature dependence.

PMID- 9644591
TI  - Interactions of DNA with fluorescent dyes: by scanning tunneling microscopy.
AB  - Genomic DNA was obtained from peripheral blood samples of healthy volunteers and
      interacted with two fluorescent dyes (i.e. Hoechst 33,258 and ethidium bromide)
      in aqueous media. These media containing DNA-dye complexes deposited on the gold
      coated mica surfaces. Then, STM images were obtained in which the STM was
      operated in air at atmospheric pressure with a tip-to-substrate bias voltage of
      250-1000 mV (sample positive) and the tunneling currents in the range of 10-20 pA
      by using etched tips of Pt/Ir, in constant current mode. Both dyes from molecular
      clusters on DNA. While, the Hoechst molecules were observed on the DNA chains at
      regular distances, the ethidium bromide molecular clusters did not.

PMID- 9644592
TI  - Structural organisations of hemoglobin and myoglobin influence their binding
      behaviour with phenothiazines.
AB  - Binding modalities of chlorpromazine and trifluoperazine, two widely used
      antipsychotic phenothiazine drugs with hemoglobin and myoglobin have been studied
      to understand how the quaternary, tertiary and secondary structural organisations
      of the proteins regulate the binding process. NaCl-induced alteration in the
      quaternary structure of hemoglobin influences its binding modality with
      phenothiazines. Minor alterations in the tertiary structure of thermally
      denatured myoglobin (denaturation temperature ranging between 30-70 degrees C) do
      not affect its affinity and the modality of binding with the drugs, but
      alterations in the secondary structure of the protein denatured at temperatures
      between 70-80 degrees C influence its binding.

PMID- 9644593
TI  - Protein stability function relations: beta-lactoglobulin-A sulphydryl group
      reactivity and its relationship to protein unfolding stability.
AB  - The effect of protein stability on the reactivity of the free sulphydryl (SH)
      group in beta-lactoglobulin-A (beta-LgA) provides a model for the study of
      protein stability-function relations (PSFR). The free energy change for protein
      unfolding (delta G(o)) and SH group exposure (delta GSH) were determined from (i)
      the urea unfolding curve for beta-LgA and (ii) the kinetics of beta-LgA
      SH/disulphide exchange with 2-pyridine disulphide (2-PDS) in 0-8 M urea (pH 3).
      Protein unfolding profiles determined from extrinsic fluorescence and SH-group
      reactivity measurements were not coincident. beta-LgA formed a stable
      intermediate (X) state in the presence of 4 M urea with delta G(o) = 20 (+/-
      0.03) kJ/mol. From the low rate of SH/disulphide exchange in 4 M urea, the SH
      group within beta-LgA was efficiently masked within the X-state. SH reactivity
      increased after beta-LgA was unfolded in 6-8 M urea with, delta GSH = 43(+/- 6.4)
      kJ/mol. Such results are discussed in terms of possible interrelationships
      between protein unfolding stability and SH reactivity in beta-LgA.

PMID- 9644594
TI  - The phage lambda terminase enzyme: 1. Reconstitution of the holoenzyme from the
      individual subunits enhances the thermal stability of the small subunit.
AB  - The terminase enzyme from bacteriophage lambda is a hetero-trimeric complex
      composed of the viral gpA and gpNu1 proteins (gpA1.gpNu1(2)) and is responsible
      for packaging a single genome within the viral capsid. Current expression systems
      for these proteins require thermal induction which may be responsible for the
      formation of insoluble aggregates observed in E. coli. We report the re-cloning
      of the terminase subunits into vectors which allow low temperature induction.
      While this has resulted in increased solubility of the large gpA subunit of the
      enzyme, the small gpNu1 subunit remains insoluble under all conditions examined.
      This paper describes the solublization of gpNu1 with guanidinium hydrochloride
      and purification of the protein to homogeneity. Reconstitution of the enzyme from
      the individually purified subunits yields a catalytically-competent complex which
      exhibits activity identical to wild-type enzyme. Thermal denaturation of the
      proteins was monitored by circular dichroism (CD) spectroscopy and demonstrates
      that while unfolding of gpA is irreversible, the gpNu1 subunit refolds into a
      conformation which is essentially identical to the pre-heated protein. Moreover,
      while denaturation of gpA is highly cooperative, the small subunit unfolds over a
      wide temperature range and with thermodynamic parameters lower than expected for
      a small globular protein. Thermally-induced denaturation of the enzyme
      reconstituted from the individual subunits is highly cooperative with no evidence
      of multiple transitions. Our data demonstrate that the terminase subunits
      directly interact in solution, and that this interaction alters the thermal
      stability of the smaller gpNu1 subunit. The implication of these results with
      respect to assembly of a catalytically competent enzyme complex are discussed.

PMID- 9644595
TI  - The phage lambda terminase enzyme: 2. Refolding of the gpNu1 subunit from the
      detergent-denatured and guanidinium hydrochloride-denatured state yields
      different oligomerization states and altered protein stabilities.
AB  - The terminase enzyme from bacteriophage lambda is responsible for packaging a
      single genome within the viral capsid. Gold and co-workers have developed a
      scheme for the solubilization of the small terminase subunit (gpNu1) from
      inclusion bodies using the strong detergent sarkosyl and purification of the
      protein to homogeneity (gpNu1SRK) (Parris et al., J Biol Chem 1994;269:13564
      13574). We have developed a similar purification scheme except that guanidinium
      hydrochloride was used to denature the insoluble protein (gpNu1GDN). The circular
      dichroism (CD) spectra of both protein preparations suggest that they are
      predominantly alpha-helical when purified and stored in Tris buffers. Moreover,
      thermal denaturation of the proteins thus purified yielded similar thermodynamic
      parameters for unfolding (T(m), delta Hm and delta Sm of unfolding of
      approximately 306 K, approximately 22 kcal/mol and approximately 70 cal/mol.K,
      respectively). Interestingly, however, when the proteins were purified and stored
      in imidazole buffers, the gpNu1SRK preparation lost a significant amount of
      secondary structure and was more stable to both thermally-induced and guanidinium
      HCl-induced denaturation than was gpNu1GDN. The purified gpNu1 monomers
      oligomerize into apparent tetramers and hexamers in solution and the distribution
      between these two oligomeric states and into higher order aggregates depends upon
      buffer composition, salt concentration and protein concentration. Moreover,
      differences in the oligomerization state of gpNu1SRK and gpNu1GDN under identical
      buffer conditions were observed. The significance of these results with respect
      to the biological role of the phage lambda gpNu1 protein are discussed.

PMID- 9644596
TI  - Laser-Raman and FT-IR spectroscopic studies of peptide-analogues of silkmoth
      chorion protein segments.
AB  - Silkmoth chorion, the proteinaceous major component of the eggshell, with
      extraordinary mechanical and physiological properties, consists of a complex set
      of proteins, which have a tripartite structure: a central, evolutionarily
      conserved, domain and two more variable 'arms'. Peptide-analogues of silkmoth
      chorion protein central domain segments have been synthesized. Laser-Raman and
      infrared spectroscopic studies suggest the preponderance of antiparallel beta
      pleated sheet structure for these peptides, both in solution and in the solid
      state.

PMID- 9644597
TI  - Radiation crosslinking of a bacterial medium-chain-length poly(hydroxyalkanoate)
      elastomer from tallow.
AB  - Pseudomonas resinovorans produces a medium-chain-length poly(hydroxyalkanoate)
      (MCL-PHA) copolymer when grown on tallow (PHA-tal). This polymer had a repeat
      unit composition ranging from C4 to C14 with some mono-unsaturation in the C12
      and C14 alkyl side chains. Thermal analysis indicated that the polymer was semi
      crystalline with a melting temperature (T(m)) of 43.5 +/- 0.2 degrees C and a
      glass transition temperature (Tg) of -43.4 +/- 2.0 degrees C. The presence of
      unsaturated side chains allowed crosslinking by gamma-irradiation. Irradiated
      polymer films had decreased solubility in organic solvents that indicated an
      increase in the crosslinking density within the film matrix. The addition of
      linseed oil to the gamma-irradiated film matrix enhanced polymer recovery while
      minimizing chain scission. Linseed oil also caused a decrease in the enthalpy of
      fusion (delta Hm) of the films (by an average of 60%) as well as enhanced
      mineralization. The effects of crosslinking on the mechanical properties and
      biodegradability of the polymer were determined. Radiation had no effect on the
      storage modulus (E') of the polymer. However, radiation doses of 25 and 50 kGy
      did increase the Young modulus of the polymer by 129 and 114%, and the tensile
      strength of the polymer by 76 and 35%, respectively. Finally, the formation of a
      higher crosslink density within the polymer matrix decreased the biodegradability
      of the PHA films.

PMID- 9644598
TI  - A structural study of beta-casein adsorbed layers at the air-water interface
      using X-ray and neutron reflectivity.
AB  - New details on the structure of beta-casein adsorbed layers, at the air-water
      interface, have been obtained using X-ray and neutron reflectivity. The
      experimental data are fitted well by a power law model and the results discussed
      in terms of the distribution of amino-acid sequences between trains, loops and
      tails. This distribution seems to be consistent with statistical theories
      established for flexible polymers. The trains are present in close proximity to
      the surface as a dense layer 8-9 A thick. At low surface coverage, the tail
      effect is negligible and the adsorbed layer is composed of nearly 60% amino-acid
      sequences in trains and the remaining in loops. When the bulk concentration is
      increased, a substantial part of the amino-acid residues has to be accommodated
      in loops and long tails; the adsorbed layer becomes more extended (80-100 A). A
      striking feature is observed for a high bulk concentration (10(-1) wt.%): trains
      are forced to eject out of the interface.

PMID- 9644599
TI  - [Antimicrobial activity of macrolides against clinical isolates].
AB  - Antimicrobial activity of 6 macrolides was determined using a micro-broth
      dilution method, against 535 clinical isolates of 22 species, which were isolated
      in 1996 from 325 facilities in Japan. Results were as follows. 1. In general,
      antimicrobial activities of 14-membered macrolides were higher than those of 16
      membered macrolides. The antimicrobial activities of 14-membered macrolides were
      in the order of clarithromycin (CAM), erythromycin (EM), roxithromycin (RXM).
      Among 16-membered macrolides, rokitamycin (RKM) was the most potent, josamycin
      (JM) was next potent followed by midecamycin (MDM). More numbers of highly
      resistant strain of > 100 micrograms/ml were recognized in 14-membered macrolides
      than in 16-membered macrorides. 2. Most of S. pyogenes (group A) strains were
      distributed in the susceptible range and almost none was found in the resistant
      range. 3. S. pneumoniae strains were distributed widely from the susceptible
      range to the highly resistant range, and as high as 37.1% fell into the high
      resistance of > 100 micrograms/ml range. 4. Against Peptostreptococcus spp. and
      MRSA, 16-membered macrolides were more effective than 14-membered macrorlides,
      and their antibacterial activities were in the order of RKM, JM, MDM. Ratio of
      high-resistant strains of > 100 micrograms/ml against 14-membered macrolides was
      much higher than that against 16-membered macrolies. 5. Most of M. (B.)
      catarrhalis strains were distributed in the susceptible range of < or = 1.56
      micrograms/ml, and most of H. influenzae strains were distributed within the
      moderately resistant and the resistant ranges. 6. In M. (B.) catarrhalis and H.
      influenzae, no correlation between macrolide resistance and beta-lactamase
      production was recognized. 7. Most of C. jejuni strains were susceptible to all
      macrolides used in this study.

PMID- 9644600
TI  - [Increase of non-amidated muropeptides in the cell wall of vancomycin-resistant
      Staphylococcus aureus (VRSA) strain Mu50].
AB  - The mechanism of resistance was studied with vancomycin-resistant Staphylococcus
      aureus (VRSA) strain Mu50. It was demonstrated that the incorporation of 14C-N
      acetylglucosamine into the cell wall of Mu50 was not suppressed in the presence
      of 8 microliters/ml of vacomycin, whereas it was completely suppressed in
      vancomycin-susceptible strains FDA209P and H-1. Increased binding of vancomycin
      to the wall of Mu50 was observed compared to the control strains: 1.7 x 10(16)
      (Mu50), 6.1 x 10(15) (209P), and 6.7 x 10(15) (H-1) vancomycin molecules/mg cell
      wall, respectively. Remarkable proportion of the cell-wall component muropeptides
      were non-amidated in the cell wall of Mu50. In concordance with this phenomena,
      peptidoglycan cross-linkage decreased strikingly in the Mu50 strain. Free D-Ala-D
      Ala residues at the end of muropeptides in the pre-existing cell wall generated
      by decreased cross-linkage seems to account for increased vancomycin binding. The
      increase of vancomycin-resistance level is presumably caused by sequestration of
      vancomycin molecules from primary target point on cell membrane. It was
      considered that at least two phenotypic changes are required for the vancomycin
      resistance in the Mu50 strain. First, as we have described previously, is the
      activated cell wall synthesis, and second, the reduction of cross-linkage of
      peptidoglycan by production of non-amidated muropeptide precursors.

PMID- 9644601
TI  - [Drug susceptibility of clinically isolated Helicobacter pylori].
AB  - Between January 1995 and March 1997, 78 Helicobacter pylori strains were isolated
      from patients with gastritis and gastric ulcer and their drug-susceptibilities to
      8 antimicrobial agents and 3 anti-ulcer drugs were determined. Imipenem was the
      most active agent and its MICs to all the strains tested were lower than 0.013
      microgram/ml. Amoxicillin, cefaclor and minocycline were active against H. pylori
      with MIC90s of 0.05 microgram/ml, 0.78 microgram/ml and 0.39 microgram/ml,
      respectively, and no resistant strains against these drugs were isolated.
      However, resistant strains to clarithromycin (isolation frequency: 9%),
      erythromycin (13%), ofloxacin (8%) and metronidazole (13%) were isolated. Triple,
      double and single resistant strains to above 4 antimicrobial agents were noted.
      No quadruple resistant strain was isolated. Frequencies of those resistance
      patterns were 14.3% (triple), 28.6% (double), and 57.1% (single), respectively.
      Seven erythromycin-resistant strains were shown to be cross-resistant to
      clarithromycin but 3 erythromycin-resistant strains were susceptible to
      clarithromycin. It seems likely that this phenomenon is caused by the fact that
      clarithromycin is more active to H. pylori than erythromycin. The MIC90 value of
      lansoprazole was lower than those of omeprazole and famotidine.

PMID- 9644602
TI  - [Clinical and bacteriological studies on panipenem/betamipron in pediatrics.
      Kanagawa Research Group for Infectious Diseases of Children].
AB  - Following its introduction into the market, PAPM/BP (panipenem/betamipron) was
      clinically studied in 188 evaluable cases out of 207 cases primarily of
      respiratory infectious diseases treated at the pediatric departments of 15
      hospitals. In the clinical evaluation, the drug proved effective in three of
      three cases of sepsis; three of three cases of suppurative meningitis; nine of
      ten cases of laryngopharyngitis, six of seven cases of tonsillitis, 56 of 63
      cases of acute bronchitis, 90 of 98 cases of pneumonia, and one of one case of
      phyothorax, all of which are respiratory infectious diseases; one of one case of
      secondary infection of a chronic respiratory disease; and two of two cases of
      lymphadenitis, which is a disease of the soft dermal structure. The overall
      efficacy rate was 91.0% (171/188 cases). In the bacteriological study, Gram
      positive bacteria were eliminated in five of five strains of S. aureus, 30 of 31
      strains of S. pneumoniae (96.8%), and three of three strains of S. pyogenes.
      Gramnegative bacteria were eliminated in 15 of 17 strains of H. influenzae
      (88.2%), three of four strains of M. catarrhalis, and two of two strains of K.
      pneumoniae. The overall elimination rate was 92.1% (70/76 strains). In the 23
      strains of S. pneumoniae that were examined, penicillin-resistant strains
      accounted for 56.5%, showing an elimination rate of 100%. No serious adverse
      effects were observed, and the incidence of adverse effects was 1.45%. As for
      abnormalities in laboratory tests, levels of GOT and GPT increased in eight cases
      (3.88%), LDH increased in one case (0.48%), and neutropenia occurred in one case
      (0.51%). These results suggest that PAMP/BP could be considered the first choice
      in the treatment of infectious diseases in pediatrics, due to its effectiveness
      and high level of safety.

PMID- 9644603
TI  - [Clinical evaluation of combination therapy with cefpirome and amikacin for
      infections associated with hematological disorders].
AB  - Cefpirome (CPR) and amikacin (AMK) were used concomitantly to treat infections
      complicated by hematological diseases. A total of 100 subjects were evaluated,
      and the allover efficacy rate was 72.0%. Acute leukemia was found in the largest
      number of patient, 55, followed by 12 cases of malignant lymphoma and 6 cases of
      chronic myelogenous leukemia. By type of infection, patients having suspected
      sepsis were the largest in number, being 50, and the efficacy rate was 68.0%. The
      efficacy rates for sepsis and pneumonia were 57.1% (7 cases) and 61.1% (18
      cases), respectively. The efficacy rates by neutrophil counts before
      administration of CPR and AMK and at 7 days after administration were both 71.9%
      in the group of less than 500/microliter, both 60.0% in the group of less than
      100/microliter. The efficacy rate was 75.0% in the group of granulocyte colony
      stimulating factor (G-CSF) concomitant usage, and 70.0% in the non-concomitant
      usage group. Concomitant treatment with CPR and AMK exhibited a high level of
      safety and efficacy rates in infections complicated by hematological diseases and
      high.

PMID- 9644604
TI  - Native American adolescents' views of fetal alcohol syndrome prevention in
      schools.
AB  - Alcohol is the most commonly abused substance among adolescents in the United
      States. Adolescent females are recognized as one group at risk for giving birth
      to babies with fetal alcohol syndrome (FAS). Sixth through eighth grade Native
      Americans were surveyed about their attitudes toward and knowledge of FAS risk
      factors and prevention strategies. Data revealed that 52% of students drank
      alcohol prior to the survey. Though sexually active, students lacked knowledge
      about the relationship between alcohol and FAS. The study revealed 1) limited
      prevention programs in middle schools and 2) the most influential factor in
      determining attitudes and decisions about alcohol use was the immediate family.
      Students felt FAS prevention is an important topic in school health education,
      noting the important role peers play in teaching and role modeling. Various
      strategies incorporating music and communication technology such as videotape and
      computer-assisted interactive tools into prevention materials are discussed.

PMID- 9644605
TI  - Trends in tobacco use among high school students in the United States, 1991-1995.
AB  - This study examined demographic characteristics of tobacco-using high school
      students in the United States from 1991 through 1995. Data about cigarette
      smoking and smokeless tobacco use among adolescent were collected in 1991, 1993,
      and 1995 using the Youth Risk Behavior Survey, part of the Youth Risk Behavior
      Surveillance System implemented by the Centers for Disease Control and
      Prevention. Data indicated current smoking increased 26.5% from 1991 to 1995 with
      one-third [31.2% (+/- 1.7)] of ninth grade students and 38.2% (+/- 3.5) of 12th
      grade students reporting current smoking in 1995. Smokeless tobacco use remained
      stable with 11.4% (+/- 1.7) of all students and one-fourth [25.1% (+/- 3.0)] of
      White male students reporting smokeless tobacco use in 1995. Many students
      already have begun using tobacco before reaching high school. Thus, interventions
      should begin well before high school to prevent adolescents from using and
      becoming addicted to tobacco.

PMID- 9644606
TI  - AIDS risk among students attending Seventh-day Adventist school, in North
      America.
AB  - In 1995, a survey was conducted among students attending 69 Seventh-day Adventist
      (SDA) high schools within the United States and Canada. The survey assessed the
      extent that these students practiced sexual and drug-use behaviors which place
      them at risk for contracting or transmitting the human immunodeficiency virus
      (HIV). A total of 1,748 respondents enrolled in grades 9 through 12 completed
      questionnaires similar to the instrument used in the 1993 Youth Risk Behavior
      Survey (YRBS). Data were collected and compared to results from the 1993 YRBS.
      Students who attended SDA parochial schools reported lower rates of sexual
      intercourse compared to YRBS school counterparts (16.3% vs. 53.1%) and lower
      rates of all substances measured. Furthermore, respondents were more likely to
      engage in substance use and sexual intercourse if they had at least one parent
      who used tobacco, alcohol, or marijuana, as reported by the students.

PMID- 9644607
TI  - From eradication to resistance: five continuing concerns about pediculosis.
AB  - A school nurse, serving in the capacity of infection control officer, is
      responsible for managing head lice infestations. The nurse's concerns on the
      student and parent levels include dispelling misconceptions about lice,
      screening, motivating correct treatment, and providing follow-up. The nurse's
      responsibility to the community as a whole also involves putting into practice
      policies that prevent the spread of infestations without promoting pediculicide
      resistance.

PMID- 9644608
TI  - Cumulative effects of prevention education on substance use among 11th grade
      students in Ohio.
AB  - This article examines participation in school-based prevention activities from a
      statewide sample of 11th grade students in Ohio. About 42% of subjects indicated
      they had never been involved in a prevention education activity. Differences
      existed in mean number of activities by both gender and White/nonWhite status.
      Popular prevention education activities included participation in D.A.R.E. (Drug
      Abuse Resistance Education) at elementary, junior high, and senior high levels,
      "Just Say No Clubs"; Quest; and Red Ribbon Week. Only a small proportion of youth
      participated exclusively in any one of these activities. An association existed
      between student participation in prevention education and level of drug
      involvement. Students in each activity had lower mean scores for drug involvement
      when compared to students who had never participated in a prevention education
      activity. Also, the lowest mean scores occurred among students who had
      participated in multiple prevention activities.

PMID- 9644609
TI  - Identifying sources of social support.

PMID- 9644610
TI  - The PREPARE approach to training clinicians in school mental health programs.

PMID- 9644612
TI  - How asthma friendly is your school? National Heart, Lung, and Blood Institute.
      National Asthma Education and Prevention Program. School Asthma Education
      Subcommittee.

PMID- 9644611
TI  - Technology and the gender gap.

PMID- 9644613
TI  - Long-term versus short-term hearing aid benefit.
AB  - This study compared hearing aid benefit obtained 6 weeks and a minimum of 1 year
      after fitting to determine if changes occurred over time. Fifteen individuals
      with mild-to-moderate sensorineural hearing losses, who were successful users of
      linear amplification, were fitted binaurally with the Resound BT2 Personal
      Hearing System. These hearing aids are programmable in two frequency bands that
      provide wide dynamic range compression (WDRC) amplification. The manufacturer's
      recommended loudness growth in octave bands (LGOB) and audiogram programming
      algorithm and fitting procedures were used. Following an initial 6-week period
      and again following a minimum of 1 year of use, the Profile of Hearing Aid
      Benefit (PHAB) was administered. Similarly, speech recognition performance was
      tested using the Connected Speech Test (CST) in a six-talker speech babble at 50
      dBA, +10 signal-to-noise (S/N); 60 dBA, +5 SNR; and 70 dBA, +2 SNR; and in quiet
      with a reverberation time of 0.78 seconds. Significant aided benefit was shown.
      These short-term benefit scores for the PHAB and CST were compared with those
      obtained after 1 year of full-time use. Results revealed no significant change in
      hearing aid benefit with long-term use, suggesting that a 6-week acclimatization
      period is sufficiently long for clinical trials of this type of WDRC
      amplification.

PMID- 9644614
TI  - Contralateral suppression of distortion product otoacoustic emissions in children
      with cystic fibrosis: effects of tobramycin.
AB  - The role of the medial efferent system in altering and/or regulating outer hair
      cell function in the mammalian cochlea has been proposed by a number of
      investigators. This study measured contralateral suppression of distortion
      product otoacoustic emissions (DPOAEs) in cystic fibrosis (CF) patients, treated
      for lung infections with low to moderate cumulative doses of tobramycin, to
      ascertain the contributions of the efferent-based mechanisms in the development
      of ototoxicity. The results showed significant suppression of DPOAEs in
      tobramycin-treated children compared to both nondrug-treated CF and normal
      children of similar ages. Since DPOAE amplitudes were comparable across the drug
      treated and control groups of subjects, pronounced DPOAE suppression in the drug
      treated group may be attributed to the instability of the cochlear amplifier
      induced by the tobramycin treatment. These findings also suggest that enhanced
      contralateral suppression may be the first sign of a developing ototoxicity.

PMID- 9644615
TI  - Vowel perception in prelingually deafened children with multichannel cochlear
      implants.
AB  - Vowel perception ability for 16 prelingually deafened children using Nucleus 22
      channel cochlear implants was studied at 12, 24, and 36 months postimplantation.
      Information transmission analysis was used to evaluate the effectiveness of the
      implants in conveying the essential cues required for accurate vowel
      identification and whether the cues used varied with experience or device use.
      Individual vowel identification varied widely with mean scores significantly
      improving between 12 and 24 months but not between 24 and 36 months. Information
      transmission scores for all vowel features (fronting, height, duration, and
      diphthongization) increased dramatically between 12 and 36 months. Results
      indicated that vowel height and vowel fronting were the most salient features for
      the subject group. There were no differences in the pattern of confusions made
      across test sessions or across groups when divided into "poor" and "good" users.
      However, there was evidence that the "good" users made better use of higher
      frequency formant information than the "poor" users. The results of the present
      study add to the accumulation of evidence pointing to the great benefit that
      cochlear implantation can provide to prelingually deafened children. Overall
      performance for the vowel recognition test used in this study was quite high and
      analysis of the childrens' errors suggested that their cochlear implants were
      reasonably effective at conveying the most essential spectral information
      required for vowel discrimination.

PMID- 9644616
TI  - Aging and word recognition in competing message.
AB  - As part of an epidemiologic study of hearing disorders in older adults, word
      recognition performance (NU-6 word lists in quiet and in competing message) was
      evaluated for 3189 adults grouped by age (48-59 years, n = 1176; 60-69 years, n =
      979; 70-79 years, n = 794; 80-92 years, n = 240). Overall, scores for all
      measures were worse for older age groups and worse for men than for women. Word
      recognition scores in competing message were poorer than word recognition scores
      in quiet for all subjects and age groups. Further, differences in scores across
      age groups and gender were greater for the word recognition test in competing
      message than for the word recognition test in quiet. Although degree of hearing
      loss accounted for the largest portion of variation in word recognition scores,
      the observed age and gender differences remained significant after adjusting for
      the degree of sensorineural hearing loss.

PMID- 9644617
TI  - Recognition of temporally distorted words by listeners with and without a
      simulated hearing loss.
AB  - In separate experiments, word recognition performance of two groups of 12 normal
      hearing young adults was investigated as a function of temporal distortion (i.e.,
      time compression ratio or reverberation time) with and without a simulated high
      frequency hearing loss (i.e., low-pass filtered at 2000 Hz). Performance
      decreased significantly as a function of increasing time compression,
      reverberation, and with the simulated hearing loss (p < .05). A statistically
      significant interaction between each of time compression ratio and reverberation
      time with the filtered listening condition was found (p < .05). This finding of
      an interactive, as opposed to a simple additive, effect of multiple distortions
      of the speech on word recognition performance suggests that loss of audibility
      alone cannot account for decrements in word recognition performance with time
      altered speech. It is suggested that this multiplicative effect for combined
      acoustic distortions is a consequence of the functional loss of the high
      frequency region of the cochlea. Not only is there a loss of audibility, but
      there is also a loss in temporal resolution capacity since it is perception
      mediated through the population of high-frequency auditory channels that has the
      best temporal resolution.

PMID- 9644618
TI  - Reliability of the Contour Test in a population of adults with hearing loss.
AB  - With the increasing popularity of hearing aids with wide dynamic range
      compression, where the goal may be to restore normal perception of loudness,
      there has been renewed interest in obtaining individual loudness judgments in a
      clinically feasible, reliable manner as part of the hearing aid evaluation. The
      purpose of the current investigation was to evaluate the test-retest reliability
      of the Contour Test of Loudness Perception. Twenty-seven adults with hearing loss
      participated in the experiment. They produced loudness judgments on two separate
      occasions. Results as assessed by the intraclass correlation statistic revealed
      that the Contour Test has adequate consistency and absolute agreement across
      frequency and loudness categories over two test sessions separated in time.
      Results are discussed in relation to previous reliability findings from other
      loudness judgment methods and other subject populations.

PMID- 9644619
TI  - Procedural considerations in the real-ear measurement of completely-in-the-canal
      instruments.
AB  - Conventional procedures for measurement of the real-ear aided response (REAR) of
      hearing aids are performed by placing the probe tube 5 mm beyond the medial tip
      of the canal portion of the earmold or shell and within 5 mm of the tympanic
      membrane. Completely-in-the-canal (CIC) instruments insert more deeply into the
      ear canal, and thus may make adherence to conventional probe-microphone
      procedures impossible. The REAR was measured at several probe tube insertion
      depths, using two insertion methods: through a probe vent and alongside the CIC
      shell. Results indicated that conventional probe insertion depth is not necessary
      for CIC instruments and may place some clients at risk for discomfort due to
      contact of the probe tube with the tympanic membrane. Placement of the probe tube
      along-side the CIC shell rather than through a probe vent resulted in slit leak
      venting effects that were highly variable across subjects. A probe tube placement
      protocol for use with CIC instruments is suggested.

PMID- 9644620
TI  - A FIT solution.
AB  - The Fusion at Inferred Threshold (FIT) test is a clinically useful procedure for
      assessing air-conduction pure-tone thresholds in any ear that may not be tested
      by conventional procedures with masking. It has not been widely reported in the
      literature. This article describes the FIT test procedure and provides four case
      studies where the FIT was used successfully to determine appropriate management
      strategies.

PMID- 9644621
TI  - Reliability issues with the Synthetic Sentence Identification test.
AB  - This investigation examined the reliability of the Synthetic Sentence
      Identification (SSI) test. An adaptive procedure was used to assess speech
      recognition thresholds (SRTs) for the SSI lists over two separate test sessions.
      The commercially available Davy Crockett passage and a multitalker babble were
      used as competition. Subjects consisted of 20 adults with normal hearing
      sensitivity. Results indicated (1) significantly higher SRTs with the multitalker
      babble, (2) significant differences in SRTs among SSI lists when using the Davy
      Crockett competition, (3) no significant learning/practice or fatigue effects
      across trials in either noise condition, and (4) high test-retest reliability
      across test sessions. Clinical implications of these data are considered.

PMID- 9644622
TI  - Auditory and auditory-visual recognition of clear and conversational speech by
      older adults.
AB  - Research has shown that speech articulated in a clear manner is easier to
      understand than conversationally spoken speech in both the auditory-only (A-only)
      and auditory-visual (AV) domains. Because this research has been conducted using
      younger adults, it is unknown whether age-related changes in auditory and/or
      visual processing affect older adults' ability to benefit when a talker speaks
      clearly. The present study examined how speaking mode (clear vs conversational)
      and presentation mode (A-only vs AV) influenced nonsense sentence recognition by
      older listeners. Results showed that neither age nor hearing loss limited the
      amount of benefit that older adults obtained from a talker speaking clearly.
      However, age was inversely correlated with identification of AV (but not A-only)
      conversational speech, even when pure-tone thresholds were controlled
      statistically.

PMID- 9644623
TI  - Effects of two repair strategies on speechreading of words and sentences.
AB  - The effectiveness of two repair strategies, repetition and paraphrasing, in
      enhancing speechreading performance was evaluated on 20 young adults with normal
      hearing using both word and sentence test stimuli. Both strategy types produced
      significant improvement, and the repeat strategy yielded the greatest gains
      overall. Paraphrasing resulted in the most enhancement for words, while
      repetition was the most effective of the two strategies with sentences. The
      inclusion of both repair strategies is recommended in communication therapy with
      the hearing impaired.

PMID- 9644624
TI  - Effect of volume expansion on the paracellular flux of lanthanum in the proximal
      tubule.
AB  - Although studies of volume expansion (VE) in the Necturus suggest a major role
      for paracellular flux in reabsorption by the proximal tubule, results from
      morphologic or electrophysiologic studies of the effect of VE on the rat proximal
      tubule suggest only a minor role for paracellular transport. In the present
      study, during in vivo microperfusion, lanthanum was used as an extracellular
      marker to determine bidirectional paracellular flux in the rat proximal tubule
      before and during 10% VE. Lanthanum itself did not affect proximal tubule
      reabsorption (delta 0.7 +/- 3.3 nl/min, LaCl3 versus saline infusion, n = 7).
      When lanthanum was added to the luminal perfusate, paracellular lanthanum efflux
      from the lumen to the interstitium was 28.9 +/- 6.6 pg/min per mm, n = 7.
      Subsequent VE significantly decreased the paracellular lumen-to-interstitium
      efflux to 12.8 +/- 8.3 pg/min per mm concomitant with a 49% decrease in proximal
      fluid reabsorption (delta -2.6 +/- 0.9 nl/min per mm, P < 0.05). When lanthanum
      was infused interstitially, by means of a chronically implanted matrix, there was
      significant paracellular lanthanum influx from the interstitium into the lumen
      (143.9 +/- 18.6 pg/min per mm, n = 4). Subsequent VE significantly increased this
      interstitium-to-lumen influx to 212.1 +/- 29.2 pg/min per mm as proximal
      reabsorption was significantly decreased by 58% (delta -2.8 +/- 0.8 nl/min per
      mm, P < 0.05). Thus, VE affects bidirectional paracellular flux in a manner that
      would decrease proximal reabsorption; paracellular efflux from the lumen to the
      interstitium was decreased, whereas paracellular influx from the interstitium to
      the lumen was increased.

PMID- 9644625
TI  - Biochemical and ultrastructural characterization of fluid transporting LLC-PK1
      microspheres.
AB  - The established renal epithelial cell line LLC-PK1 (proximal tubule) started to
      form multicellular spheroids within 24 h when grown in agar overlay culture. The
      spheroids, average diameter 100 to 350 microns, were free-floating with a
      butterfly-like structure due to the formation of several hollow microspheres. The
      microspheres were lined with polarized epithelial cells that had an abundance of
      microvilli protruding into the external medium and a well developed vacuolar
      apparatus, including coated pits, endocytotic vacuoles, and lysosomes. The
      microspheres were sealed between lumen and the surrounding medium by tight
      junctions and fluctuated in size due to fluid being transported in an apical-to
      basal direction. Vasopressin was found to stimulate this transport, whereas the
      addition of ouabain or HgCl2 inhibited both spheroid growth and fluctuation in
      size with time. Biochemical assays of brush-border and lysosomal marker enzymes
      demonstrated an increase in enzyme activity during spheroid formation and growth.
      The most dramatic changes were observed for dipeptidyl peptidase IV (two- to
      threefold after 1 d and 53.5-fold after 15 d), reflecting the cellular
      polarization and brush-border formation during spheroid formation. When the
      typical lysosomal enzymes were compared, the activity of peptide bond splitting
      enzymes increased earlier than others. In conclusion, LLC-PK1 spheroids capable
      of forming microspheres represent an in vitro manifestation of specialized
      epithelial properties maintained in cell culture, thus providing a tool for
      studying renal physiologic mechanisms at a cellular level.

PMID- 9644626
TI  - Renal endothelin system in polycystic kidney disease.
AB  - Polycystic kidney disease (PKD) is characterized by interstitial fibrosis and
      formation of renal cysts. Interestingly, interstitial fibrosis and renal cyst
      formation were also seen in human endothelin-1 (ET-1) transgenic mice. This
      study, therefore, analyzes the tissue distribution of ET-1, the tissue
      concentrations of ET-1, as well as the expression of ET receptor subtypes in the
      kidneys of a rat model of PKD: Han:SPRD rats. Six-week-old heterozygous (cy/+)
      and homozygous (cy/cy), as well as 6-mo-old heterozygous (cy/+) Han:SPRD rats and
      the corresponding age-matched Sprague Dawley littermates (SD) (+/+) were
      analyzed. Furthermore, the acute effects of the mixed (A/B) endothelin receptor
      antagonist bosentan on hemodynamic and renal function were investigated in 6-mo
      old, conscious, chronically instrumented (cy/+) rats. The kidneys of affected
      rats showed significantly elevated tissue levels of ET-1 compared with age
      matched controls (3.5 +/- 0.3-fold in young cy/cy rats, P < 0.01; 1.4 +/- 0.2
      fold in young cy/+ rats, P < 0.01; 6.2 +/- 0.4-fold in old cy/+ rats, P < 0.001)
      due to a highly increased ET-1 synthesis within the epithelial cells of the
      cysts. Analyzing tissue sections from patients with typical autosomal dominant
      PKD demonstrated a high ET-1 expression within the epithelial cells of the cysts
      as well. Scatchard analysis revealed a markedly decreased ETA and ETB receptor
      density in all groups of affected rats. The acute blockade of both endothelin
      receptor subtypes using bosentan in 6-mo-old heterozygous PKD rats led to a
      significant decrease in mean arterial BP (MAP) (-19.7 +/- 2.1 mmHg, P < 0.05) and
      GFR (-41 +/- 5%, P < 0.005). Renal blood flow (RBF) was significantly increased
      (+2.1 +/- 0.5 ml/min, P < 0.05) after bosentan, whereas bosentan had no effect on
      MAP, GFR, and RBF in age-matched controls. These data show that the paracrine
      renal endothelin system is activated in PKD and participates in the regulation of
      MAP, GFR, RBF, and possibly contributes to renal cyst formation and fibrosis.

PMID- 9644627
TI  - cDNA cloning and expression of a novel family of enzymes with calcium-independent
      phospholipase A2 and lysophospholipase activities.
AB  - Previous studies have suggested that activation of calcium-independent PLA2
      (CaIPLA2) is an early event in cell death after hypoxic injury in proximal tubule
      cells. An approximately 28-kD CaIPLA2 with preferential activity toward
      plasmalogen phospholipids has been recently purified from rabbit kidney cortex
      (D. Portilla and G. Dai, J Biol Chem 271, 15,451-15,457, 1996). Their report
      describes the cloning of a full-length rat cDNA encoding CaIPLA2, using sequences
      derived from the purified rabbit kidney cortex enzyme. In addition, cDNA from
      rabbit kidney that encode the rabbit homologue of the enzyme and a closely
      related isoform were isolated. The rat cDNA is predicted to encode an
      approximately 24-kD protein, and each cDNA contains the sequence G-F-S-Q-G, which
      fits the active site consensus sequence G-X-S-X-G of carboxylesterases. Several
      lines of evidence (DNA sequence comparison, Southern blot analysis, and
      examination of the expressed sequence tag database) show that CaIPLA2 enzymes are
      encoded by a multigene family in rats, mice, rabbits, and humans. Northern
      analysis of various tissues from the rat indicated that the CaIPLA2 gene is
      ubiquitously expressed, with highest mRNA abundance observed in the kidney and
      small intestine. The rat CaIPLA2 cDNA, when expressed in a baculovirus expression
      system, and the purified rabbit kidney cortex protein exhibit both CaIPLA2 and
      lysophospholipase activities. The cloned CaIPLA2 cDNA are expected to aid in
      understanding the role of CaIPLA2 in cell death after hypoxic/ischemic cell
      injury.

PMID- 9644628
TI  - IL-4 and IL-13 augment cytokine- and CD40-induced RANTES production by human
      renal tubular epithelial cells in vitro.
AB  - Local production of cytokines by infiltrating monocytes/macrophages and Th1 and
      Th2 cells is of importance in renal allograft rejection. Activated Th1 cells can
      produce interleukin-2 (IL-2), interferon-gamma (IFN-gamma), and tumor necrosis
      factor (TNF), whereas Th2 cells produce IL-4 and IL-13, which inhibit Th1 cells.
      Furthermore, activated T cells express the costimulatory molecule CD40-ligand.
      During renal allograft rejection, the chemokine RANTES is detected in both
      infiltrating mononuclear cells and tubular epithelium. It has been shown
      previously that stimulation of proximal tubular epithelial cells (PTEC) with
      cytokines or CD40-ligand results in production of RANTES. The present study
      investigates the influence of Th1 and Th2 cytokines on RANTES production by
      activated PTEC. RANTES was not detectable in supernatants of human PTEC
      stimulated with IL-2, IL-4, IL-10, or IL-13 alone. Likewise, combination of these
      cytokines with IL-1 alpha, IFN-gamma, or TNF-alpha, respectively, did not result
      in detectable RANTES production. IL-2 and IL-10 had no significant effect on
      RANTES production by activated PTEC. IL-4 or IL-13 in combination with IL-1 alpha
      + IFN-gamma or IFN-gamma + TNF-alpha resulted in a two- to fourfold augmentation
      of RANTES production, ranging from 2.2 +/- 0.2 to 35 +/- 2 ng/ml in different
      cell lines. CD40-activated PTEC stimulated with IL-4 or IL-13 produced six to ten
      times more RANTES (ranging from 7.9 +/- 1.9 to 62 +/- 3.5 ng/ml in different cell
      lines) compared with CD40-activated cells alone. Because RANTES production is
      augmented by IL-4 and IL-13, this study suggests that during rejection, direct
      cellular contact between activated Th2 cells and tubular epithelial cells
      amplifies the local inflammatory reaction in the kidney.

PMID- 9644629
TI  - Interleukin-15, a leukocyte activator and growth factor, is produced by cortical
      tubular epithelial cells.
AB  - Many renal diseases, including transplant rejection, are mediated by mononuclear
      cells. Interleukin-15 (IL-15) has been recently described as a cytokine with IL-2
      like activity. IL-15 is an effective leukocyte growth factor, activator, and
      chemoattractant. In rejected human kidney allografts, elevated IL-15, but not IL
      2, mRNA is expressed, suggesting a role for IL-15 in the rejection process. The
      aim of this study was to investigate whether human cortical tubular epithelial
      cells (HTC) are able to produce IL-15 and whether IL-15 expression is regulated
      by inflammatory mediators. HTC were isolated and characterized, and IL-15
      expression was analyzed by reverse transcription-PCR, enzyme-linked immunosorbent
      assay, and bioactivity. It was found that HTC constitutively express IL-15. Upon
      stimulation of HTC with interferon-gamma (IFN gamma), the levels of both mRNA and
      protein increased up to twofold. In contrast, lipopolysaccharide, IL-1, IL-2, and
      tumor necrosis factor-alpha had no detectable effect. IFN gamma action on HTC was
      dose-dependent from concentrations of 5 U/ml, reaching a plateau at 50 U/ml. HTC
      supernatants induced proliferation of the T cell line CTLD, which could be
      partially blocked (50%) by specific IL-15 antibodies. This study shows that IL-15
      is secreted by HTC and that the Th1-cytokine IFN gamma upregulates IL-15
      expression. This suggests that HTC play a role in cell-mediated renal diseases by
      releasing IL-15.

PMID- 9644630
TI  - Upregulation of renal and systemic cyclooxygenase-2 in patients with active lupus
      nephritis.
AB  - In lupus nephritis (LN), renal thromboxane A2 (TXA2) production is increased, and
      inhibition of TXA2 activity improves renal function. In patients with LN, renal
      function depends very much on vasodilatory prostaglandins, and indeed inhibiting
      the prostaglandin-forming enzyme cyclooxygenase (COX) with aspirin or related
      compounds was detrimental on renal hemodynamics in these patients. There are no
      data so far on whether the excessive TXA2 production in LN derives from
      upregulation of type I or type II isoforms of COX. It was found that TXB2
      synthesis and COX-2 gene expression were higher in peripheral blood mononuclear
      cells from patients with active LN compared to patients in the inactive form of
      the disease and to healthy subjects. Unlike COX-2, levels of COX-1 mRNA were
      comparable in lupus patients and control subjects and were not influenced by the
      disease activity. Immunoperoxidase studies on kidney biopsies showed COX-1
      staining in glomerular arterioles and other renal vessels, with no evident
      difference between lupus biopsies and control specimens taken from either
      individuals who were free of renal disease or patients with non-lupus
      nephropathies. In contrast, COX-2 staining was definitely stronger in specimens
      from patients with active LN than control specimens. In active LN, COX-2-specific
      staining was localized mainly in the glomeruli, with a weaker signal on tubuli
      and in the interstitium. Double-staining studies with an antibody against the
      macrophage marker CD68 and an anti-COX-2 antibody definitely showed that COX-2
      and CD68 often colocalized on the same cell, with only occasional glomerular COX
      2-stained mesangial areas. Patients with non-lupus nephropathies had no increase
      in renal COX-2 expression. These results indicate that COX-2 upregulation is a
      specific finding of active LN and that monocytes infiltrating the glomeruli
      contribute to the exaggerated local synthesis of TXA2. If this is correct, COX-2
      may soon become a target for therapeutic intervention in this disease.

PMID- 9644631
TI  - In progressive nephropathies, overload of tubular cells with filtered proteins
      translates glomerular permeability dysfunction into cellular signals of
      interstitial inflammation.
AB  - Progression to end-stage renal failure is the final common pathway of many forms
      of glomerular disease, independent of the type of initial insult. Progressive
      glomerulopathies have in common persistently high levels of urinary protein
      excretion and tubulointerstitial lesions at biopsy. Among the cellular mechanisms
      that may determine progression regardless of etiology, the traffic of excess
      proteins filtered from glomerulus in renal tubule may have functional importance
      by initiating interstitial inflammation in the early phase of parenchymal injury.
      This study analyzes the time course and sites of protein accumulation and
      interstitial cellular infiltration in two different models of proteinuric
      nephropathies. In remnant kidneys after 5/6 renal mass ablation, albumin and IgG
      accumulation by proximal tubular cells was visualized in the early stage,
      preceding interstitial infiltration of MHC-II-positive cells and macrophages. By
      double-staining, infiltrates developed at or near tubules containing
      intracellular IgG or luminal casts. This relationship persisted thereafter
      despite more irregular distribution of infiltrate. Similar patterns were found in
      an immune model (passive Heymann nephritis), indicating that the interstitial
      inflammatory reaction develops at the sites of protein overload, regardless of
      the type of glomerular injury. Osteopontin was detectable in cells of proximal
      tubules congested with protein in both models at sites of interstitial
      infiltration, and by virtue of its chemoattractive action this is likely mediator
      of a proximal tubule-dependent inflammatory pathway in response to protein load.
      Protein overload of tubules is a key candidate process translating glomerular
      protein leakage into cellular signals of interstitial inflammation. Mechanisms
      underlying the proinflammatory response of tubular cells to protein challenge in
      diseased kidney should be explored, as well as ways of limiting protein
      reabsorption/deposition to prevent consequent inflammation and progressive
      disease.

PMID- 9644632
TI  - Mineralized bone loss at different sites in dialysis patients: implications for
      prevention.
AB  - To characterize the magnitude and location of mineralized bone loss, 40 patients
      (20 men, 20 women, 29 white, 11 black) with clinically significant renal
      osteodystrophy who could be unambiguously classified based on histologic criteria
      as having osteitis fibrosa (OF; 20 cases) or osteomalacia (OM; 20 cases) were
      studied; they had been on maintenance hemodialysis for 4.6 +/- 3.0 yr. One
      hundred forty-two healthy women of similar age and ethnic composition served as
      control subjects. In all subjects, the proportions of mineralized bone, osteoid,
      and porosity (nonbone soft tissue) were measured separately in cortical and
      cancellous bone tissue, from intact full-thickness biopsies of the ilium,
      representative of the axial skeleton. The results were related to the volumes of
      cortical and cancellous bone tissue separately and to the volume of the entire
      biopsy core. Approximately three-quarters of the patients had measurements in the
      appendicular skeleton by single photon absorptiometry of the radius and
      morphometry of the metacarpal. Disease effects did not differ significantly
      between ethnic groups. Mineralized cortical bone volume (per unit of core volume)
      was reduced by approximately 45% in both patient groups. Mineralized cancellous
      bone volume was significantly increased by 36% in the patients with OF and
      nonsignificantly reduced by 9% in the patients with OM; however, the reduction in
      the latter patients was significant in relation to tissue volume. The combined
      total deficit for both types of iliac bone was approximately 20% in the patients
      with OF and approximately 40% in the patients with OM. Significant reductions in
      appendicular cortical bone were demonstrated in both patient groups at both
      measurement sites. Regardless of the current histologic classification, the major
      structural abnormality in the skeleton is generalized thinning of cortical bone
      due to increased net endocortical resorption, the most characteristic effect on
      bone of hyperparathyroidism. Protection of the skeleton from the adverse
      consequences of renal failure will require therapeutic intervention in patients
      with no symptoms of either renal or bone disease.

PMID- 9644633
TI  - Involvement of R-cadherin in the early stage of glomerulogenesis.
AB  - The earliest commitment to the formation of glomeruli is recognizable in S-shaped
      bodies. Although cell-cell adhesion seems likely to play a crucial role in this
      process, how glomerular epithelial cells segregate from the other parts of the
      nephron is unknown. In this study, immunofluorescence microscopy and monoclonal
      antibodies specific for mouse R-, E-, P- and N-cadherins were used to examine
      which of these adhesion molecules are involved in glomerulogenesis of the mouse
      kidney. Weak R-cadherin staining was first found in the vesicle stage, becoming
      restricted to glomerular visceral epithelial cells (VEC) during the S-shaped body
      stage. The intensity of this staining became stronger in the capillary loop
      stage, whereas parietal epithelial cells (PEC) and tubular cells did not stain.
      In the maturing stage, VEC gradually lost their staining for R-cadherin. E
      cadherin was detected in ureteric buds and the upper limb of S-shaped bodies.
      From the capillary loop to the maturing stage, anti-E-cadherin stained epithelial
      cells in all tubule segments, but no label was seen in VEC or PEC. P-cadherin was
      also stained in the ureteric buds and in the upper limb of S-shaped bodies. N
      Cadherin was weakly stained in cells at the vesicle stage, but thereafter
      staining of N-cadherin was not detected at any stage of glomerular formation.
      Immunoelectron microscopy of differentiating VEC was performed using antibodies
      specific to alpha-catenin, which is associated with cadherin. Subsequently,
      immunogold particles identifying alpha-catenin were localized on junctions
      between primary processes of VEC. These findings indicate that R-cadherin is
      uniquely expressed in differentiating VEC, suggesting an important role in the
      early stages of glomerulogenesis.

PMID- 9644634
TI  - Potassium citrate/citric acid intake improves renal function in rats with
      polycystic kidney disease.
AB  - Polycystic kidney disease (PKD) has been shown to be exacerbated by acidosis or a
      low potassium intake, and there is evidence that administration of alkali might
      have a beneficial effect. This study determined whether ingestion of potassium
      citrate and citric acid would ameliorate PKD. Healthy normal and heterozygous
      littermate Han:SPRD rats with autosomal dominant PKD were provided with either
      tap water or 55 mM K3citrate/67 mM citric acid solution (KCitr) to drink starting
      at the age of 1 mo. Renal clearance measurements and histologic assessments were
      performed when the rats were 3 mo old. KCitr intake did not affect body weight or
      urine flow, but completely prevented the decline in GFR found in untreated rats
      with PKD. In rats that drank tap water, left kidney GFR averaged (in
      microliter/min per 100 g body wt) 503 +/- 78 (n = 9) in normal animals and 242 +/
      56 (n = 6) in rats with PKD. In rats that drank KCitr, GFR averaged 562 +/- 123
      (n = 7) in normal animals and 534 +/- 103 (n = 7) in rats with PKD. Kidneys of
      rats with PKD were approximately double normal size. KCitr treatment did not
      affect kidney size, but led to fewer interstitial abnormalities and smaller cysts
      in cystic kidneys. KCitr ingestion led to a significantly lower (P < 0.001)
      plasma [K+] in rats with PKD (3.3 +/- 0.2 versus 4.1 +/- 0.2 mEq/L in rats on tap
      water). Chronic KCitr intake in the young heterozygous Han:SPRD rat with PKD
      yields a modest improvement of kidney histology and a dramatic improvement in
      GFR. The mechanism of action of KCitr and the long-term effects of this treatment
      on renal structure and function in PKD deserve further study.

PMID- 9644635
TI  - Characterization of dimethylguanosine, phenylethylamine, and phenylacetic acid as
      inhibitors of Ca2+ ATPase in end-stage renal failure.
AB  - The activity of the plasma membrane Ca2+ ATPase of chronic renal failure patients
      is decreased by circulating inhibitors yet to be characterized. In this study,
      inhibitors of Ca2+ ATPase were isolated from ultrafiltrate of patients with end
      stage renal failure. They were identified as dimethylguanosine, phenylethylamine,
      and phenylacetic acid by chromatography and mass spectrometry. Ca2+ ATPase
      activity was measured spectrophotometrically as the difference in hydrolysis of
      ATP in the presence and absence of Ca2+ with different concentrations of ATP and
      the isolated substances. All of the identified compounds are sufficiently
      lipophilic to penetrate the blood-brain barrier and to accumulate in cerebral
      tissue. The inhibitory effects of these agents were additive. The apparent K(m)
      values for ATP and Ca2+ were not altered by these substances, suggesting a
      noncompetitive mechanism of inhibition. In plasma of healthy subjects, the
      substances were not detectable. The Ca2+ ATPase inhibitors identified may play a
      role in the pathophysiology of end-stage renal failure and, potentially, in
      monitoring toxic effects on cellular Ca2+ metabolism in renal failure.

PMID- 9644636
TI  - Outcome of renal replacement therapy in antineutrophil cytoplasmic antibody
      associated systemic vasculitis.
AB  - Antineutrophil cytoplasmic antibody-associated systemic vasculitis (AASV)
      frequently leads to end-stage renal disease (ESRD). Potentially fatal disease
      activity can continue after the onset of ESRD in both dialysis and transplant
      patients, despite the immunosuppressive effects of uremia and rejection
      prophylaxis, leading to concerns that such patients have greater morbidity and
      mortality. To assess the outcome of AASV patients receiving renal replacement
      therapy, a retrospective analysis of 59 patients from our unit who received
      chronic dialysis, renal transplantation, or both, was performed. The survival of
      AASV patients with ESRD was comparable to national registry controls, as were
      both graft and patient survival after renal transplantation. Ther is no evidence
      that standard immunosuppressive protocols should be altered for AASV patients
      receiving renal transplants. The rate of relapse of vasculitis for patients on
      chronic dialysis and after transplantation was 0.09 and 0.02 per patient per
      year, respectively. These rates are lower than those of other series and support
      the contention that continued immunosuppression after ESRD, as practiced in our
      unit, is warranted. Relapses usually responded to cyclophosphamide and high-dose
      prednisolone treatment. Significantly, vasculitic flare-ups in dialysis patients
      were sometimes initially misdiagnosed as dialysis complications, leading to fatal
      delays in effective treatment. Follow-up by physicians experienced in the
      diagnosis and treatment of vasculitis activity should continue in these patients.

PMID- 9644637
TI  - Dipyridamole decreases renal phosphate leak and augments serum phosphorus in
      patients with low renal phosphate threshold.
AB  - It has been shown that an acute infusion of dipyridamole increased renal
      phosphate reabsorption in rats and humans. A prospective study was performed to
      determine whether chronic treatment by dipyridamole given orally could decrease
      renal phosphate leak and increase serum phosphorus in patients with idiopathic
      low renal phosphate threshold (TmPO4/GFR < 0.77 mM). Sixty-four patients with low
      TmPO4/GFR were included and treated with dipyridamole (75 mg, 4 times daily) for
      more than 12 mo. Serum phosphorus, TmPO4/GFR, parathyroid hormone, serum calcium,
      and 1,25-dihydroxyvitamin D were measured sequentially before treatment, and
      after 3, 6 to 9, and 12 mo of treatment. Under chronic treatment with
      dipyridamole, TmPO4/GFR and serum phosphorus significantly increased in 80% of
      patients within 3 mo, with maximal values reached within 9 mo. This improvement
      persisted after 12 mo of treatment. In 28 patients, 1,25-dihydroxyvitamin D
      concentrations were above the normal range (> 42 pg/ml) and normalized in
      parallel with the increase of serum phosphorus. The 24-h calcium excretion (which
      was initially increased in patients with high vitamin D concentrations) and
      urolithiasis decreased under treatment. Ionized serum calcium and parathyroid
      hormone remained unchanged. After 2 yr, treatment was discontinued in three
      patients; serum phosphorus and TmPO4/GFR decreased within 1 mo after
      discontinuation. Dipyridamole at a dose of 75 mg 4 times daily increases low
      TmPO4/GFR and improves hypophosphatemia in patients with renal phosphate losses
      and can be used to treat these patients.

PMID- 9644638
TI  - Familial aggregation of renal disease in a population-based case-control study.
AB  - Family history of renal disease has been associated with an increased risk of end
      stage renal disease (ESRD). It is uncertain whether this risk is mediated by
      familial aggregation of risk factors for ESRD, such as diabetes and hypertension.
      The association of ESRD with familial aggregation of renal disease was examined
      in a large, population-based case-control study conducted in Maryland, Virginia,
      West Virginia, and Washington, DC. The number of first-degree relatives who were
      affected with any type of renal disease was compared between 689 newly treated
      ESRD patients registered in the Medicare ESRD program (92% of all eligible
      incident cases presenting between January and July of 1991) and 361 control
      subjects without ESRD who were selected by random-digit dialing (90% response
      rate). Patients and control subjects were frequency matched by age; patients with
      ESRD caused by polycystic kidney disease and other known hereditary kidney
      diseases were excluded. Analysis was conducted using multiple logistic
      regression. After controlling for the proband's age, gender, race, family size,
      socioeconomic status, and personal and family histories of diabetes and
      hypertension, having one first-degree relative with renal disease increased the
      odds of ESRD by 1.3 (95% confidence interval, 0.7 to 2.6) and having two or more
      affected first-degree relatives increased the odds of ESRD by 10.4 (95%
      confidence interval, 2.7 to 40.2). These data support familial aggregation of
      renal disease in excess of that predicted by clustering of diabetes and
      hypertension within families, suggesting that either genetic susceptibility or
      environmental exposures shared within families increase the risk of developing
      ESRD. This risk is also much higher when two or more first-degree relatives have
      renal disease. Unraveling the molecular basis of this increase in risk may
      provide new avenues for treatment and prevention of ESRD.

PMID- 9644639
TI  - Intermediate-density lipoprotein as an independent risk factor for aortic
      atherosclerosis in hemodialysis patients.
AB  - Patients with chronic renal failure often show accumulation of intermediate
      density lipoprotein (IDL). Because recent studies have emphasized the
      atherogenicity of IDL in the general population, we evaluated the relationship
      between this lipoprotein and aortic atherosclerosis in uremic patients treated
      with hemodialysis. Aortic pulse wave velocity (PWV) was measured as a noninvasive
      index of sclerotic change of aorta in 205 hemodialysis patients and 184 age- and
      gender-matched healthy subjects. Fasting plasma lipoproteins were fractionated by
      ultracentrifugation into very low-density lipoprotein (VLDL), IDL, LDL, and HDL.
      Plasma lipoprotein (a) (Lp(a)) was measured by a latex immunoturbidimetric assay.
      Aortic PWV was significantly higher in the hemodialysis patients than in the
      control subjects. The hemodialysis group showed a significant increase in VLDL
      and IDL cholesterol, whereas their LDL and HDL cholesterol were lower than the
      control levels. Lp(a) levels did not differ between the two groups. In the
      hemodialysis population, VLDL, IDL, and LDL cholesterol correlated positively
      with aortic PWV adjusted for age, gender, smoking, and BP, whereas Lp(a) did not.
      Multiple regression analyses indicated that plasma triglycerides, independent of
      HDL cholesterol, had a significant association with aortic PWV in the
      hemodialysis patients but not in the control subjects. Further analyses revealed
      that aortic PWV in the hemodialysis patients had a significant and independent
      association with IDL cholesterol, whereas aortic PWV in the control subjects had
      significant and independent associations with HDL cholesterol and Lp(a). These
      results demonstrate that IDL is the lipoprotein fraction most closely associated
      with aortic PWV in the hemodialysis patients.

PMID- 9644640
TI  - Increased peritoneal membrane transport is associated with decreased patient and
      technique survival for continuous peritoneal dialysis patients. The Canada-USA
      (CANUSA) Peritoneal Dialysis Study Group.
AB  - The objective of this study was to evaluate the association of peritoneal
      membrane transport with technique and patient survival. In the Canada-USA
      prospective cohort study of adequacy of continuous ambulatory peritoneal dialysis
      (CAPD), a peritoneal equilibrium test (PET) was performed approximately 1 mo
      after initiation of dialysis; patients were defined as high (H), high average
      (HA), low average (LA), and low (L) transporters. The Cox proportional hazards
      method evaluated the association of technique and patient survival with
      independent variables (demographic and clinical variables, nutrition, adequacy,
      and transport status). Among 606 patients evaluated by PET, there were 41 L, 192
      LA, 280 HA, and 93 H. The 2-yr technique survival probabilities were 94, 76, 72,
      and 68% for L, LA, HA, and H, respectively (P = 0.04). The 2-yr patient survival
      probabilities were 91, 80, 72, and 71% for L, LA, HA, and H, respectively (P =
      0.11). The 2-yr probabilities of both patient and technique survival were 86, 61,
      52, and 48% for L, LA, HA, and H, respectively (P = 0.006). The relative risk of
      either technique failure or death, compared to L, was 2.54 for LA, 3.39 for HA,
      and 4.00 for H. The mean drain volumes (liters) in the PET were 2.53, 2.45, 2.33,
      and 2.16 for L, LA, HA, and H, respectively (P < 0.001). After 1 mo CAPD
      treatment, the mean 24-h drain volumes (liters) were 9.38, 8.93, 8.59, and 8.22
      for L, LA, HA, and H, respectively (P < 0.001); the mean 24-h peritoneal albumin
      losses (g) were 3.1, 3.9, 4.3, and 5.6 for L, LA, HA, and H, respectively (P <
      0.001). The mean serum albumin values (g/L) were 37.8, 36.2, 33.8, and 32.8 for
      L, LA, HA, and H, respectively (P < 0.001). Among CAPD patients, higher
      peritoneal transport is associated with increased risk of either technique
      failure or death. The decreased drain volume, increased albumin loss, and
      decreased serum albumin concentration suggest volume overload and malnutrition as
      mechanisms. Use of nocturnal cycling peritoneal dialysis should be considered in
      H and HA transporters.

PMID- 9644641
TI  - Neoral conversion from Sandimmune in maintenance renal transplant patients: an
      individualized approach.
AB  - When converting maintenance renal allograft recipients from Sandimmune
      (cyclosporin A [CsA]) to Neoral (CsA-microemulsion [CsA-ME]), a dose conversion
      ratio of 1:1 may not be optimal, in part because of the variability in absorption
      of the CsA formulation of cyclosporine. After conversion using a 1:1 dose ratio,
      an individualized approach to the management of dosing was applied. In this
      article, close monitoring, which began at the time of conversion, and rapid
      response to potentially meaningful changes in cyclosporine trough levels early in
      the postconversion course were used to maintain patients' cyclosporine troughs at
      preconversion levels. The results of cyclosporine dose changes after converting
      stable, maintenance renal transplant patients from CsA (once daily and twice
      daily) to CsA-ME (twice daily) during 52 wk of follow-up are reported. Most
      patients (87.2%) required CsA-ME dose reduction to maintain preconversion trough
      levels, and 64% of the patients attained their CsA-ME maintenance dose by study
      week 4. Logistic regression analysis identified one significant predictor
      concerning the week 52 CsA-ME dose: patients converted from CsA doses > or = 4.0
      mg/kg per d were more likely to require dose reduction (P < 0.0001). Although
      firm guidelines for dose modification after conversion from CsA to CsA-ME cannot
      be provided because of the individual nature of cyclosporine absorption, an
      individualized approach to patient management is recommended. Patients with
      higher CsA doses before conversion are particularly likely to require dose
      reduction early in the postconversion course. With CsA-ME, good absorbers of
      cyclosporine remain good absorbers, or become better absorbers, whereas poor
      absorbers become good absorbers.

PMID- 9644642
TI  - The prognostic significance of specific arterial lesions in acute renal allograft
      rejection.
AB  - Diagnosis of allograft dysfunction relies on the assessment of arterial lesions.
      This study was designed to evaluate the prognostic significance of common
      specific vascular lesions in acute allograft rejection. Renal allograft biopsies
      (n = 111) with acute cellular rejection were scored for endarteritis, mononuclear
      cell adherence to endothelial cells, endothelial activation, fibrinoid necrosis,
      foam cells, and intimal fibrosis. These vascular lesions and other classic
      histologic features were correlated with outcome. Rejection with endarteritis
      (found in 54% of biopsies) was less responsive to steroid treatment than
      rejection without endarteritis, as judged by recovery of creatinine in 3 wk (P =
      0.03). Larger numbers of sampled arteries improved the predictive accuracy.
      Sticking of mononuclear cells to endothelial cells also correlated with steroid
      resistance (P < 0.05). Rejection with or without endarteritis responded to
      OKT3/antithymocyte globulin treatment equally well (61% versus 65%,
      respectively). Rejection with fibrinoid arterial necrosis (4% of biopsies) did
      not respond to either steroids or antibodies (0%). One-year graft failure was 21%
      without endarteritis, 28% with endarteritis, and 100% with fibrinoid necrosis.
      Activated endothelial cells and interstitial hemorrhage were associated with
      endarteritis and graft failure (all P < 0.05). None of the other scored features
      had any statistically significant correlation with outcome. Thus, specific
      arterial lesions (endarteritis, fibrinoid necrosis, activated endothelial cells,
      mononuclear cell margination) and interstitial hemorrhage, but not the extent of
      the interstitial infiltrate or tubulitis, are correlated with response to
      antirejection therapy and/or 1-yr clinical outcome. Grading systems for
      therapeutic trials and clinical management should emphasize scoring of specific
      vascular lesions.

PMID- 9644643
TI  - High rate of acute rejections in renal allograft recipients with thrombophilic
      risk factors.
AB  - Inherited and acquired thrombophilic disorders predispose patients for
      thromboembolic and probably other occlusive vascular events that occur when
      additional risk factors play in concert. Because acute rejections in renal
      transplant recipients may reflect vascular events, and an impairment of the
      fibrinolytic system in immunosuppressed patients has been previously described,
      the implications of genetic or acquired risk factors of thrombophilia for the
      occurrence of early acute rejections after kidney transplantation were evaluated.
      The following risk factors of thrombophilia were determined in 97 patients after
      cadaveric kidney transplantation: factor V Leiden mutation, protein S, protein C,
      and antithrombin deficiency. In a retrospective analysis, the prevalence of acute
      rejections, the histologic classification when rejection episodes had been
      confirmed by biopsy, and other vascular complications were evaluated. In 21 of
      the 97 patients, an inherited or acquired risk factor of thrombophilia was
      detected. Prevalence of acute rejections was 71% in the first 6 mo after
      transplantation in patients with a thrombophilic disorder and significantly
      higher compared with patients without thrombophilia (41%; P = 0.017). The
      distribution of classic risk factors associated with acute rejections, such as
      number of human leukocyte antigen mismatches or percentage of panel-reactive
      antibodies, was similar in patients with and without thrombophilia. In the eight
      patients with thrombophilia and histologically proven acute rejection, four
      patients had an acute vascular rejection, and in two patients a vascular
      involvement was suspected. Furthermore, prevalence of cerebral or coronary
      vascular disease, or venous thromboembolic complications, was significantly
      higher in patients with a thrombophilic clotting defect (67%) compared with
      patients with normal hemostasis parameters (28%; P < 0.002). It is concluded that
      renal allograft recipients with thrombophilia are at risk of developing an acute
      rejection or other vascular event. Although the determination of thrombotic risk
      factors was performed at least 3 mo after an acute rejection episode, it can be
      presumed that acute rejection episodes are associated with subsequent coagulatory
      abnormalities with further consequences for transplant survival. Thus,
      pretransplant evaluation of genetic and acquired risk factors of thrombophilia is
      recommended.

PMID- 9644644
TI  - Silent infection in clotted hemodialysis access grafts.
AB  - Thrombotic and infectious complications are frequent causes of hemodialysis
      vascular access failure and contribute considerably to the cost of care for
      chronic hemodialysis patients. Although there is clear indication for removal of
      patent grafts in unresolved bacteremia, there are no guidelines for the
      management of clotted nonfunctioning grafts. To evaluate for the existence and
      clinical relevance of silent infection in clotted nonfunctioning hemodialysis
      grafts, a study was conducted with a series of 20 hemodialysis patients who
      presented with fever (15 patients), or fever and clinical signs of sepsis (five
      patients), in whom the source of infection was not immediately localized to any
      organ system. Comparison was made with 21 asymptomatic patients with clotted
      grafts who served as control subjects. All patients and control subjects came
      from a pool of 115 chronic hemodialysis patients in an outpatient hemodialysis
      unit in the Houston metropolitan area, who were on hemodialysis for a period of
      time ranging from 3 to 15 yr. Indium scans were performed, followed by removal of
      the clotted grafts in all patients and control subjects. Bacterial cultures of
      the recovered surgical material and blood were done concomitantly in all study
      participants. Indium scans showed positive uptake in or around the clotted grafts
      in all of the patients and in 15 of the control subjects. Purulent material was
      found in the grafts in all patients and in 13 of 15 indium scan-positive control
      subjects. When positive, blood culture pathogens were identical to those cultured
      from the graft material in all instances. The predominant pathogens were
      Staphylococcus aureus, followed by Staphylococcus epidermidis. There was no
      evidence of graft infection in the control subjects if indium scan was negative.
      Chart review dating back to the start of dialysis revealed five past infectious
      episodes in the patient group, compared with four in the control group. These
      findings suggest that clotted nonfunctioning grafts are frequent harbingers of
      infection. They should be suspected as the source of infection in every
      hemodialysis patient that presents with fever, even in the absence of clinical
      signs of graft site infection.

PMID- 9644645
TI  - Beta-adrenoceptor-stimulated renin release is blunted in old rats.
AB  - Plasma renin activity (PRA) was similar in young versus old male Sprague Dawley
      rats under unstressed conditions (1.3 +/- 0.2 versus 1.8 +/- 0.3 ng angiotensin
      I/ml per min). Airjet stress increases PRA in young but not old rats (13.9 +/-
      3.8 versus 2.9 +/- 0.8 ng angiotensin I/ml per min), respectively. This response
      is ablated in young rats by beta-adrenoceptor blockade, suggesting that the
      increased PRA is mediated by beta-adrenoceptors, and this response was blunted in
      old rats.

PMID- 9644646
TI  - Protecting single-kidney allografts from long-term functional deterioration.

PMID- 9644647
TI  - Primary focal segmental glomerulosclerosis.

PMID- 9644648
TI  - Renal tubular secretion of potassium in the normal dog.

PMID- 9644649
TI  - Statistical science and quantitative understanding.
AB  - Authors of papers in biological journals need to make their uses of statistical
      methods and software explicit and maximally comprehensible. Editors and referees
      have important responsibilities for this. Inexact use of technical terminology
      causes confusion. Computer software is invaluable but not infallible. Graphical
      presentation should not conceal numerical results. Tests of statistical
      significance should be reserved for specific needs, which will rarely include
      multiple comparison procedures. Experiments that involve repeated measurements
      need special care in statistical analysis. Full attention should be given to
      principles of statistical estimation as well as to choice of appropriate
      statistical technique. At all times, ethical standards of scientific integrity
      must contribute to precision and clarity. Clinical research that neglects well
      established statistical principles may be intrinsically unethical.

PMID- 9644650
TI  - Comparison of sex differences in guinea-pig maximization test for detection of
      skin-sensitizing potential using OECD recommended positive control sensitizers.
AB  - Both male and female guinea pigs are widely used in tests to detect the skin
      sensitizing potential of new chemicals. The aim of the present study was to
      investigate the influence of the animal gender on sensitization rates, with the
      guinea-pig maximization test (GPMT) using OECD recommended positive control
      sensitizers, and the differences of the density of Langerhans cells in male and
      female guinea pigs. The sensitization rates of males and females challenged with
      HCA, MBT or benzocaine gave almost the same results. There were no statistical
      differences between the mean responses of males and females. These results were
      confirmed by rechallenge with the OECD recommended positive controls.
      Furthermore, the density of Langerhans cells in abdominal epidermis in males
      (1229 +/- 45 cells/mm2) was the same as that in females (1242 +/- 89 cells/mm2).
      These results indicate that there is no significant influence of guinea-pig
      gender in the assessment of skin-sensitizing potential using the GPMT.

PMID- 9644651
TI  - Formation of 8-oxodeoxyguanosine in liver DNA and hepatic injury by peroxisome
      proliferator clofibrate and perfluorodecanoic acid in rats.
AB  - In this study, we examined whether the production of hydrogen peroxide by
      peroxisome proliferators causes oxidative DNA damage in the form of 8
      oxodeoxyguanosine (8-oxodG) and hepatic injury, and whether it is related to
      their tumor-promoting or carcinogenic activities in female rats treated with the
      peroxisome proliferators clofibrate and perfluorodecanoic acid (PFDA). Clofibrate
      has tumor-promoting and carcinogenic activities, whereas PFDA does not. We also
      tested whether peroxisome proliferators directly induce mutagenic events in
      Salmonella typhimurium strains TA 98 and TA 1537. Rats were treated either by 5%
      clofibrate in diet or by an i.p. injection of corn oil containing 10 mg/kg body
      weight of PFDA every week for 2 or 8 weeks. 8-OxodG in liver DNA was analyzed by
      HPLC coupled with an electrochemical detector. Hepatic injury was evidenced by
      liver enlargement and by levels of serum enzymes, aspartate aminotransferase
      (AST) and alanine aminotransferase (ALT), and hepatic gamma-glutamylpeptidase
      (gamma-GT) activity. Clofibrate and PFDA increased the activity of catalase about
      or less than 2-fold, whereas FAO activity was increased about 6 to 7-fold by
      clofibrate and about 3 to 4-fold by PFDA. Neither clofibrate nor PFDA induced
      mutation at any dose tested. Clofibrate significantly increased the formation of
      8-oxodG, but PFDA only slightly increased. Serum AST and ALT levels, and hepatic
      gamma-GT activity were not significantly changed at both time points, whereas the
      ratio of liver/body weight was significantly increased by clofibrate and PFDA at
      8 weeks. These data imply that the magnitude of the production of hydrogen
      peroxide-generated FAO is related to the induction of oxidative DNA damage by
      peroxisome proliferators, and their tumor-promoting or carcinogenic activities.
      However, the effect of hydrogen peroxide in hepatic injury is not clear.

PMID- 9644652
TI  - Involvement of vitamin D in lead-induced cutaneous calcification in rodents.
AB  - Experimental cutaneous calcification was induced by a subcutaneous injection of
      lead acetate in parathyroidectomized (PTX) rats and vitamin D-deficient rats
      whose plasma calcium concentrations were controlled by diets containing various
      amounts of calcium. Although, in PTX rats, the calcium content of the calcified
      plaque induced by lead acetate was correlated with their plasma calcium
      concentration, calcium content of the calcified plaque in vitamin D-deficient
      rats with normocalcemia was significantly lower than those in control and PTX
      rats with normocalcemia. A subcutaneous administration of 1 alpha,25
      dihydroxyvitamin D3 (1 alpha,25(OH)2D3) following the lead acetate injection
      increased calcium content of the calcified plaque in vitamin D-deficient mice,
      suggesting the involvement of vitamin D in the cutaneous calcification. As the
      synthesis of osteocalcin, osteopontin and interleukin-1 (IL-1) receptor is well
      known to be increased by 1 alpha,25(OH)2D3, gene expressions of mRNAs of these
      proteins were examined in the skin with calcified plaque by reverse transcription
      polymerase chain reaction (RT-PCR) analysis. These mRNA expressions in the skin
      with calcified plaque were increased by a subcutaneous administration of 1
      alpha,25(OH)2D3 following the lead acetate injection. On the contrary, they
      decreased in vitamin D-deficient mice. These findings suggest that vitamin D is
      directly involved in the process of experimental calcification.

PMID- 9644653
TI  - Effect of 4-phenyl-1,3-dithia-2-thioxo-cyclopent-4-ene on liver injury induced by
      repeated exposure to galactosamine plus carbon tetrachloride in rats.
AB  - The protective effects of 1,3-dithia-2-thioxo-cyclopent-4-ene (DT827A),4-phenyl
      1,3-dithia-2-thioxo-cyclopent- 4-ene (DT827B) and 4-(4-fluorophenyl)-1,3-dithia-2
      thioxo-cyclopent-4-ene (DT827C) on liver injury induced by D-galactosamine plus
      carbon tetrachloride (D-GalN + CCl4) and that of DT827B on liver injury induced
      by thioacetamide were studied using male rats. Out of the three DT827 series of
      compounds, DT827B was more effective on liver injury induced by the combination
      exposure to D-GalN + CCl4 for 4 weeks, and accordingly the following two
      experiments were carried out using DT827B only. Twelve-week administration of
      DT827B at dose levels of 5, 10 and 20 mg/kg/day revealed a therapeutic effect
      against liver injury induced by D-GalN + CCl4 dose-dependently, and another
      twelve-week administration of DT827B at the same three dose levels also revealed
      a therapeutic effect against liver injury induced by thioacetamide dose
      dependently. A hepatoprotective potential of DT827B was suggested under the
      conditions of these studies.

PMID- 9644654
TI  - Prolongation of PT and APTT under excessive anticoagulant in plasma from rats and
      dogs.
AB  - Prothrombin time (PT) and activated partial thromboplastin time (APTT) were
      studied under excessive sodium citrate using the plasma from rats and beagle
      dogs. Addition of sodium citrate into the plasma caused a prolongation of PT and
      APTT. The prolongation was dependent on the concentration of sodium citrate or
      calculated hematocrit. The degree of prolongation was more severe in rats than in
      dogs, and in APTT than in PT. These results suggest that an artificial
      prolongation of PT and APTT occurs under excessive sodium citrate (e.g., elevated
      hematocrit), and that the degree differs between species and between parameters.

PMID- 9644655
TI  - [New role of stress protein heme oxygenase--its relationship with
      physiopathology].

PMID- 9644656
TI  - [Application of new technology to toxicology: dynamic analysis of hematopoietic
      stem cells-BUUV method].

PMID- 9644657
TI  - [Risk evaluation of neurotoxicity].

PMID- 9644658
TI  - [Endocrine disrupters and toxicology--tests for detection and evaluation of
      endocrine disrutptive actions].

PMID- 9644659
TI  - [International coordination of guidelines for genetic toxicity tests-- trends in
      ICH and OECD (second report)].

PMID- 9644661
TI  - [Angle heterophoria: fiction or reality].

PMID- 9644660
TI  - [Everything depends on gold].

PMID- 9644663
TI  - [Determining visual acuity using European normal values: scientific principles
      and possibilities for automatic measurement].
AB  - PSYCHOMETRIC FUNCTION: According to the European standard EN ISO 8596 the Landolt
      C in 8 different orientations has to be used to measure visual acuity. With
      decreasing size of the Landolt-C the hit rate declines from 100% to the chance
      level of 12.5%. This gradual transition is described by the "psychometric
      function". The steepest point of the psychometric function is in the middle
      between 100 and 12.5, i.e., at 56.25%. This point of the psychometric function
      (approximated by 5 of 8 Landolt-Cs) has been selected as the threshold for visual
      acuity, because it is there that the visual acuity is influenced least by
      (incidental) fluctuations. The subject has to answer by forced choice; a response
      like "I cannot detect anything" is not acceptable. "NORMAL" VISUAL ACUITY: Cannot
      be assigned to a certain value, like 1.0 or 6/6. With the standard test
      procedure, visually healthy, young subjects achieve a visual acuity of about 2.0
      or 12/6, while in senior subjects 0.5 (3/6) may be "normal". AVERAGING VISUAL
      ACUITY: Logarithmic, not arithmetic, scaling of visual acuity approximates the
      perceptual metric. Consequently, visual acuity values may not be averaged
      arithmetically. Instead, three steps are required: all values have to be
      converted to logarithms, then averaged, and finally the average can be
      reconverted. Geometric averaging is equivalent. "MINIMUM ANGLE OF RESOLUTION" NOT
      NECESSARY: MAR is the reciprocal of visual acuity. In many studies, clinical
      outcome has been assessed using log(MAR). Though statistically correct, this term
      is unnecessary, as log(acuity) has identical statistical properties. Furthermore,
      log(MAR) is contra-intuitive as its value becomes smaller when vision improves.
      COMPUTER-ASSISTED INSTRUMENTATION: Facilitates complying with the EN ISO 8596.
      For instance, the Freiburg Visual Acuity Test relieves the examiner from
      observing whether 5 responses have been correct, and that not more than 8 tests
      are given per level.

PMID- 9644664
TI  - [Objective assessment of minimum visual acuity by suppression of optokinetic
      nystagmus].
AB  - PURPOSE: To develop and to validate an objective method which allows an
      estimation of the visual acuity (VA) of adults. METHODS: A horizontal optokinetic
      nystagmus (OKN) was elicited by a vertical rectangular grating presented on a PC
      screen and was recorded by an infrared reflection method. Superimposition of
      three stationary black detection stimuli was used to suppress the OKN. The size
      of these stimuli was increased every two seconds, in ten steps. Suppression of
      the OKN was taken as an indication that the stimuli were detected. The relation
      between the smallest effective stimulus and logVA was evaluated in 65 healthy
      volunteers (130 eyes) with artificially reduced VA and 425 cooperative patients
      (842 eyes) whose VA was reduced due to different etiologies. The tolerance
      intervals of logVA related to the discrete detection stimuli were calculated.
      RESULTS: The method allows an estimation of the least expectable VA in steps of
      0.8, 0.32, 0.25, 0.12, 0.1, 0.06, 0.03 und 0.025 due to the smallest value of
      three trials. The least VA of strabismic amblyopic eyes can only be estimated in
      steps of 0.16, 0.06, and 0.02. A VA > 0.02 can be proven with high reliability.
      CONCLUSION: The method allows a clinically useful, objective estimation of the
      least VA without observer bias in non-amblyopic eyes.

PMID- 9644665
TI  - [Improved fixation of unilateral suture operation of the rectus medialis muscle
      of the amblyopic eye].
AB  - BACKGROUND: Strabismus surgery influences the retinal fixation positively, as
      described by Bohme, Ehrich and Cuppers. Fadenoperation (Posterior Fixation) of
      the medial rectus muscle allows a more specific approach. It reduces the
      influence of overadduction and latent-type nystagmus on the retinal fixation,
      which becomes more central and more controlled after such an operation. PATIENTS:
      This effect is very marked in infants up to 2 years of age, but still significant
      in older children with intolerance for occlusion, and motility-dependent
      excentric fixation. About half of the 70 cases observed reached a useful fixation
      and acuity by "surgical pleoptics". With respect to the otherwise poor prognosis
      of these cases, this result can be regarded as favourable.

PMID- 9644666
TI  - [Changes in subjective cyclodeviation and objective cycloposition after modified
      Harada-Ito operation in acquired trochlear paralysis].
AB  - BACKGROUND: After recently published own investigations on subjective and
      objective cyclorotatory changes following inferior oblique recession for inferior
      oblique overaction, it was our aim to determine and to compare subjective and
      objective cyclorotatory changes following a modified Harada-Ito procedure for
      acquired trochlear palsy. PATIENTS AND METHODS: Eight patients suffering from
      acquired uni-(n = 3) or bilateral (n = 5) trochlear palsy were investigated
      before surgery and 1 day, 3 days and 4 months after surgery. Subjective
      cyclodeviation was assessed by Harms' tangent scale. Objective cycloposition was
      measured by means of fundus cyclometry using an infrared Scanning Laser
      Ophthalmoscope. RESULTS: The immediate postoperative incyclorotatory effect was
      12 degrees in the unilateral group and 18 degrees in the bilateral group.
      Subjective and objective changes were nearly equal in both groups, with a
      subjective over-effect of 1 degree. After two days of binocular stimulation a
      marked regression of the surgical effect was found which still increased after
      four months. The long term incyclorotatory effect was subjectively and
      objectively nearly equal in the unilateral group which showed a relaps of
      subjective excyclodeviation of 5 degrees: in the bilateral group, the subjective
      effect was more pronounced than the objective effect, the immediate postoperative
      over-effect being disappeared. CONCLUSIONS: In contrast to our results concerning
      inferior oblique muscle recession for strabismus sursoadductorius, subjective and
      objective cyclorotatory changes did not differ grossly following a modified
      Harada-Ito procedure. Subjective and objective short and long term regression was
      confirmed which objectively exceeded the amount of over-correction. As the
      underlying cause mechanical and sensory mechanisms are discussed.

PMID- 9644667
TI  - [Orthoptic problems after macular rotation with and without muscle surgery].
AB  - BACKGROUND: In spite of new therapeutic approaches the treatment of age related
      macular degeneration remains unsatisfying. Macular rotation is so far only a
      rarely employed surgical procedure, where the macula is translocated to an area
      with intact retinal pigment epithelium. The aim of this study was to elucidate
      the orthoptic problems of macular rotation and describe possible treatment
      modalities. PATIENTS AND METHOD: Between February and July of 1997 a macular
      rotation was performed in 8 patients with exsudative macular degeneration,
      followed by silicone oil removal and implantation of an intraocular lens. In 3
      out of 8 patients the oblique muscles were transposed at the beginning of the
      surgery to produce an excylotropia. In all patients visual acuity for distance
      and near was determined pre- and postoperatively along with a complete orthoptic
      status including measuring of cyclotropia. Mean postoperative follow-up was 5.5
      months. RESULTS: Due to the unilateral ectopia of the macula all patients
      presented with a postoperative strabismus with vertical deviation of 2 degrees to
      10 degrees. The change of the visual axis resulted in a displacement of the
      pupillary reflex. The patients described a cyclotropia of 12 degrees to 45
      degrees corresponding to the ophthalmoscopically estimated angle of retinal
      rotation. Patients after surgery of the oblique muscles showed less cyclotropia
      with an angle of 12 degrees to 20 degrees. They were less disturbed by diplopia
      and tilted visual impression than those without muscle surgery. All patients
      exhibited an abnormal head position with chin up and tilt to the side of the
      operated eye. CONCLUSION: Macular rotation always causes diplopia because of the
      unilateral ectopia with cyclotropia and vertical deviation. These problems can be
      considerably reduced by combining macular rotation surgery with oblique muscles
      surgery. It may well be that in the future these problems can be completely
      resolved by additional surgery on the rectus muscles.

PMID- 9644668
TI  - [Normal accommodative convergence excess--long-term follow-up of conservative
      therapy with bifocal eyeglasses].
AB  - BACKGROUND: In patients with normaccommodative convergence excess it is possible
      to reduce or eliminate the excess of accommodative convergence by adding plus
      lenses. The resulting reduction of near deviation can lead to an improvement in
      the quality of binocular vision at near, and also to a better compensation of an
      esophoria at near. The aim of the paper was to study long term results in
      patients with small angle esotropia and esophoria and accommodative convergence
      excess treated by bifocals. METHODS: Clinical data of 91 patients were analysed
      retrospectively. Among them were 13 patients with esophoria, 32 patients with
      microesotropia and 46 with microesotropia and a phoric component. An orthoptic
      status was performed every three months and at every examination it was tried to
      reduce the added plus lenses. The mean follow up was 5.6 +/- 2.4 years (range:
      1.1-13.2). RESULTS: The mean onset of strabismus was similar in all groups: i.e.
      2.5 (+/- 1.7) years. The patients received their first bifocals on average 3.4
      (+/- 1.9) years later. In 40 of the 91 patients the near addition could be
      stopped because of sufficient decrease of accommodative convergence excess during
      the follow-up period. The convergence excess decreased continuously in all
      patients with esophoria and microesotropia and the additional plus lenses could
      be stopped on average after 6.4 (3.5-8.4) years (esophoria) and 5.0 (2.6-8.1)
      years (microesotropia) respectively. In patients with microesotropia and an
      additional phoric deviation bifocals were only partly successful to reduce the
      convergence excess. The basic angle decompensated in more than half of the
      patients (27 out of 46) and was operated in 14 cases by unilateral
      resection/recession procedure. After the operation the convergence excess
      decreased rapidly and the bifocals could be stopped after 4.4 (3.4-7.4) years. In
      the remaining 19 cases it was possible to reduced the convergence excess with
      bifocals in 8 patients after about 8.1 (4.1-9.3) years and in some of the
      remaining 11 cases a Fadenoperation has been suggested. CONCLUSION: While wearing
      bifocals the accommodative convergence excess decreased completely in patients
      with esophoria and microesotropia. In the condition with markedly reduced
      binocular vision and a large phoric component at far and near, the convergence
      excess decreased only in some of the patients while wearing bifocals.
      Conventional strabismus surgery to reduce the basic angle has a positive
      influence. A Fadenoperation is only necessary in a few cases.

PMID- 9644669
TI  - [Fixation disparity with the Pola pointing test: not representative for eye
      position under natural viewing conditions].
AB  - BACKGROUND: According to certain findings obtained with the Zeiss Polatest, H.J.
      Haase defined a "Fixation Disparity Type One". In this diagnosis, the
      "Zeigertest" is particularly important. The Zeigertest consists of a central ring
      presented to both eyes for fixation, a vertical clock hand presented to the right
      eye and two markings at the six and twelve o'clock positions presented to the
      left eye. All parts are surrounded by a binocularly visible frame. Subjects with
      a "Fixation Disparity Type One" see a misalignment between the clock hand and the
      peripheral markings. We investigated (1) whether the perceived misalignment
      correlated with an objective deviation of the eyes from orthovergence and (2)
      whether subjects with a "Fixation Disparity Type One" had a deviation of the eyes
      from orthovergence when looking at a natural, i.e., fully fusionable object.
      SUBJECTS AND METHODS: Out of 303 medical students, 10 subjects with a "Fixation
      Disparity Type One" were selected and asked to indicate the perceived alignment
      or misalignment in the Zeigertest with a laser pointer. Two subjects without
      fixation disparity served as controls. The position of both eyes was recorded
      using the search coil technique. One of the 10 subjects with "Fixation Disparity
      Type One" had to be excluded due to excessive blinking. Experiment 1: In the
      beginning all parts of the Zeigertest were presented to both eyes (natural
      viewing condition). Then, the object for one of the eyes was switched off leaving
      the frame as the only fusional stimulus. The outcome variable was a refixation
      movement of the other eye. This experiment is similar to the unilateral cover
      test. Experiment 2: In the beginning all parts of the Zeigertest were presented
      to both eyes (natural viewing condition). Then, the original Zeigertest was
      switched on (clock hand presented only to the right eye, peripheral markings only
      to the left eye). The outcome variable was a change of vergence. RESULTS:
      Experiment 1: A significant refixation movement did not occur in any of the
      subjects. Experiment 2. In all 9 subjects with "Fixation Disparity Type One" the
      vergence changed significantly between 2.4 and 14.9 arcmin. The change of
      vergence correlated significantly with the angle of the perceived misalignment
      between clock hand and peripheral markings. CONCLUSION: A fixation disparity
      ascertained at the Zeigertest does not indicate a fixation disparity under
      natural viewing conditions.

PMID- 9644670
TI  - [Measuring the effect of eyeglasses on determination of squint angle with
      Purkinje reflexes and the prism cover test].
AB  - BACKGROUND: The alternating prism and cover test is the conventional test for the
      measurement of the angle of strabismus. The error induced by the prismatic effect
      of glasses is typically about 27-30%/10 D. Alternatively, the angle of strabismus
      can be measured with methods based on Purkinje reflex positions. This study
      examines the differences between three such options, taking into account the
      influence of glasses. MATERIALS AND METHODS: The studied system comprised the
      eyes with or without glasses, a fixation object and a device for recording the
      eye position: in the case of the alternate prism and cover test, a prism bar was
      required; in the case of a Purkinje reflex based device, light sources for
      generation of reflexes and a camera for the documentation of the reflex positions
      were used. Measurements performed on model eyes and computer ray traces were used
      to analyze and compare the options. RESULTS: When a single corneal reflex is
      used, the misalignment of the corneal axis can be measured; the error in this
      measurement due to the prismatic effect of glasses was 7.6%/10 D, the smallest
      found in this study. The individual Hirschberg ratio can be determined by
      monocular measurements in three gaze directions. CONCLUSIONS: The angle of
      strabismus can be measured with Purkinje reflex based methods if the fundamental
      differences between these methods and the alternate prism and cover test, and if
      the influence of glasses and other sources of error are accounted for.

PMID- 9644672
TI  - [Experiences with hemangiopericytoma in cranial base surgery].
AB  - BACKGROUND: Haemangiopericytomas are rare vascular neoplasms which show either
      slow local tumour growth or aggressive progression in size with a high tendency
      of recurrence and metastasis. Manifestations of haemangiopericytomas in the area
      of the nose and sinuses are supposed to have a relatively benign course. To date
      clinical and histological parameters for prognosis are uncertain. Therefore in a
      quite large number of cases only the clinical course allows to evaluate the
      dignity of a haemangiopericytoma. PATIENTS AND RESULTS: We present our experience
      with five haemanglopericytomas in contact with the skull base out of a total
      number of 457 skull base tumours. The site of origin of these five
      haemangiopericytomas were: nasal septum, pterygopalatine fossa, oronasopharynx,
      temporal bone, and parotid gland. All neoplasms showed primary or recurrent tumor
      in contact with the skull base and an intracranial extension was observed twice.
      One patient died postoperatively of a cerebral infarction. Three patients showed
      one or more recurrences which were treated surgically. In one case 5 recurrences
      occurred. Despite of 4 surgical procedures within a period of 15 months, the
      tumour could be controlled only for a short period of time, and the patient died
      16 months after the first operation. CONCLUSION: One has to consider that
      haemangiopericytomas of the head and neck show a potential malignant course. The
      vascular tumor may recur decades later. Adequate therapy and life-long follow-up
      are therefore mandatory in haemangiopericytomas. Complete surgical resection of
      the tumour is usually the treatment of choice, in spite of the high degree of
      surgical skill required, especially in advanced tumour and in case of recurrence.

PMID- 9644671
TI  - [The Vibrant Soundbridge System: a new kind of hearing aid for sensorineural
      hearing loss. 1: Function and initial clinical experiences].
AB  - INTRODUCTION: Patients suffering from moderate to severe cochlear hearing
      impairment can not be considered for cochlear implantation on account of their
      relatively good residual hearing. Conventional hearing aids, on the other hand,
      have considerable disadvantages which clearly limit the benefit for these
      patients, e.g. feedback, sound distortion, unfavorable conditions for frequency
      transfer, occlusion, and recurrent infections of the auditory canal. In addition,
      many patients complain about a poor speech intelligibility in noise. VIBRANT
      SOUNDBRIDGE HEARING PROSTHESIS: Implantable hearing aids offer a new approach for
      improved auditory rehabilitation. The Vibrant Soundbridge system is based on an
      electromagnetic system, which is linked directly to the intact ossicular chain.
      Due to the high sound quality and the high frequency characteristic this system
      is ideally suited for the above-mentioned patient group. The usual disadvantages
      of conventional hearing aids can be avoided. Externally visible is merely the
      audio processor, which is worn in the retroauricular area and covered by hair.
      This processor transfers data and power via magnetic attachment transcutaneously.
      PATIENT POOL: During a European multicenter clinical study, 19 patients were
      implanted at MHH since February 1997. No significant complications occurred.
      RESULTS: In all patients, postoperative unaided pure tone threshold was unaltered
      in comparison with the preoperative recordings. The use of the audio processor
      leads to a significant functional gain, particularly in the high frequencies. The
      patients report about undistorted hearing resulting in a better speech
      understanding even in situations with loud background noise. CONCLUSION: The
      preliminary results show a promising new approach to the use of hearing
      prostheses for patients suffering from moderate to severe sensorineural hearing
      loss.

PMID- 9644673
TI  - [Rhinosurgical concept in management of fronto-basal defects with cerebrospinal
      rhinorrhea].
AB  - BACKGROUND: Cerebrospinal fluid (CSF) leak, with its potential infectious
      complications remains today a challenge in diagnosis and surgical treatment. With
      the introduction of endonasal microsurgery, new minimally invasive techniques for
      the repair of these defects have been pioneered. Nasal approaches to the anterior
      skull base include external-transfacial as well as endonasal approaches for
      reconstruction. It is important to have multiple possible approaches for the
      correction so that the optimal method for the individual pathology may be
      selected. The purpose of this paper is to clarify the decision process for
      selecting the safest procedure with the least possible morbidity and functional
      compromise. METHOD: In a retrospective study we assessed a group of 69 patients
      treated from 1988 to 1996. Patient records, CT scans, postoperative clinical
      follow-up and a questionnaire, sent to the patients, were evaluated. The various
      external and endonasal approaches are presented and the closure techniques are
      discussed in detail. RESULTS: Of the 69 operations, 40 (58%) were external and 29
      (42%) were endonasal. There were three failures in the external approach group
      (4.4%) and no failures in the endonasal group. No major complications in the
      intraoperative or postoperative course occurred. Of importance, olfaction was
      retained in 94% of patients in at least one side. The average duration of
      hospitalization was 6 days. CONCLUSIONS: Nasal approaches to the anterior skull
      base for treatment of CSF leaks are highly effective, safe, and cause minimal
      morbidity. The optimal surgical approach is chosen according to the precise
      location and extent of the defect. We are now increasing using endonasal
      microsurgical approaches. The open, transfacial approaches are still indicated
      for fractures of the posterior wall of the frontal sinus as well as larger multi
      fragmented fractures of the anterior skull base.

PMID- 9644674
TI  - [Effect of adenoid hyperplasia on nasal airflow].
AB  - BACKGROUND: Adenoid hyperplasia is one of the most common reasons for nasal
      obstruction in childhood. The consequences of a nasopharyngeal obstruction on the
      airflow in the nasal cavity and the epipharynx were investigated. MATERIALS AND
      METHODS: In a model of a nose we conducted experiments with adenoids of different
      size, documenting their influence on inspiratory and expiratory nasal flow.
      Rhinoresistometry was performed to obtain further information concerning
      resistance and turbulence. RESULTS: The flow experiments showed no alterations of
      the inspiratory nasal flow regardless of adenoid size. Instead the adenoid had a
      significant influence on the direction of the expiratory nasal flow in the
      cavity. Depending on the extension of the hyperplasia, parts of the nasal cavity
      were excluded from the flow. Rhinoresistometry showed that relation between
      nasopharyngeal obstruction and nasal resistance was nonlinear. CONCLUSION:
      Adenoid hyperplasia affects only expiratory nasal flow. In our model a critical
      mass seemed to be reached in case of more than 60% nasopharyngeal obstruction. A
      narrowing of the epipharynx up to 50% of its volume has no significant effects on
      nasal resistance.

PMID- 9644675
TI  - [Computer-assisted surgery in the ENT specialty. Developments and experiences
      from the first decade].
AB  - BACKGROUND: Computer-Assisted-Surgery (CAS) names a method that allows
      intraoperative navigation in the surgical field based on digital image data like
      CT, MRT, MRA, DSA and others. A computer processes the image data in real time
      and is intraoperatively connected to a measuring system for coordinate
      determination. CAS is used in ENT surgery since 1986. The authors developed
      several generations of CAS systems. METHODS: In a first approach, a passive robot
      arm was applied. Self-developed electromechanical and infrared optical coordinate
      measuring devices followed. RESULTS: CAS was applied to several fields of
      otorhinolaryngologic surgery including the paranasal sinuses, the orbit, the
      rhinobasis and otobasis and other. CAS was found to be useful for surgery of
      acoustic neuromas, the paranasal sinuses in cases of massive disease or revision
      surgery, decompression of orbit or optiv nerve, extraction of deep seated foreign
      bodies, stereotaxy-like biopsies, for educational purposes and others.
      CONCLUSIONS: CAS in its current state of development is a useful tool that can be
      routinely applied. However, further technical development is necessary.

PMID- 9644676
TI  - [Surgery in benign parotid tumors: individually adapted or standardized radical
      interventions?].
AB  - BACKGROUND: Several authors demand emphatically that the minimal operative
      procedure in benign parotid gland tumors has to be a superficial parotidectomy.
      MATERIAL: Of a consecutive series of 372 patients with benign parotid tumors
      treated in our department between 1973-1996 81% of the patients could be followed
      up 1-24 years. in 10.9% a total parotidectomy was performed, in 16% a lateral
      parotidectomy and in 73.1% a simple extirpation of the tumor (often taking away a
      small margin of surrounding parotid parenchyma). The operating microscope and
      microsurgical techniques were used in all of these operations. RESULTS: Of all
      the followed-up patients 2.3% developed a recurrence. There were no recurrences
      of cystadenolymphomas or of rare types of adenomas. Recurrences of primary
      treated pleomorphic adenomas occurred in 3.0%. In recurrent pleomorphic adenomas
      a further recurrence could be seen in 7.4% of the cases. The over-all incidence
      of permanent facial nerve weakness was 2.1%: 0.7% after extirpation, 3.3% after
      lateral parotidectomy and 9.7% after total parotidectomy. we observed in 6.3% a
      gustatory sweating. CONCLUSION: Our data prove that with simple extirpation
      similar results compared to lateral parotidectomy can be achieved concerning
      recurrence, function of the facial nerve and the Frey's syndrome. We suggest a
      surgical management adapted to the extent, the size and the location of the
      parotid gland tumors. In our opinion lateral or total parotidectomy should be
      reserved for tumors of larger amount or deep located tumors.

PMID- 9644677
TI  - [Possible application of a signal enhancer for duplex ultrasound in
      otorhinolaryngology].
AB  - BACKGROUND: Vascularization is a characteristic of malignant tumor growth. It is
      possible to distinguish between benign and malignant tumors and lymph nodes of
      the head and the neck by their pattern of blood vessels which can be detected by
      color image ultrasonography. Unfortunately this detection is often unsuccessful
      because the vessels are too small. METHOD: Four cases (lymph node metastasis,
      chronic lymph node inflammation, Morbus Hodgkin, cancer of the floor of the
      mouth) are demonstrated. The vascularization of the masses was detected before
      and after the injection of Levovist, a contrast agent which is known to amplify
      the duplex signal up to 25 dB. RESULTS: In all of the demonstrated cases, a
      similar pattern of intranodal vessels was detected before the application of
      Levovist. After the injection an enhancement of the duplex signal could always be
      detected within the first minute and differences of the intratumoral pattern of
      the blood vessels between the cases could be identified. DISCUSSION: Levovist
      results in an increased detection of intratumoral blood vessels detected by color
      image ultrasonography. Further studies are necessary to check whether its
      application results in an increase of the specificity of the examination.

PMID- 9644678
TI  - [Interesting case no. 12. Rhabdomyosarcoma of the petrous bone with infiltration
      of the facial nerve].

PMID- 9644679
TI  - [History of diaphanoscopy. Pictures from the history of otorhinolaryngology,
      illustrated by instruments from the collection of the Ingolstadt German Medical
      History Museum].
AB  - BACKGROUND: In 1854 the Spanish singing teacher Manuel Garcia succeeded in
      inspecting his own larynx. In 1857 the neurologist Ludwig Turck in Vienna,
      without knowledge of Garcia's achievement, had been experimenting on laryngoscopy
      with his patients using a small mirror and sunlight. When in the winter of 1857
      1858 he had to suspend his experiments for lack of sunlight, he lent his mirror
      to physiologist Johann Czermak in Budapest. Czermak, using artificial light
      reflected by a perforated mirror, developed modern laryngoscopy within a few
      weeks and made it a clinically valuable method. He described it in March 1858 as
      his own invention. This was the beginning of a an embittered fight with Turck
      about whose development had priority. DIAPHANOSCOPY OF THE LARYNX: During his
      very first studies on laryngoscopy Czermak noticed that the interior of the
      larynx could be inspected very well when the neck was illuminated by a strong
      light from without and the mirror was held in the dark pharynx. The tissue would
      then appear transilluminated in a glowing deep red. When sufficiently bright
      electric lamps became available in 1889, Rudolph Voltolini in Breslau, Germany,
      took up the transillumination of the larynx and even carried out some minor
      intralaryngeal operations using this method. Although suitable diaphanoscopes
      were soon on the market this technique was not widely adopted. It was ony used
      once in 1954 (Pellnitz et al.) for diagnosing early stages of laryngeal cancer.
      DIAPHANOSCOPY OF THE PARANASAL SINUSES: Voltolini in Breslau and Cozzolino in
      Naples experimented independently of each other with small electric lamps with
      the aim of finding new techniques of rhinoscopy. Both of them placed their lamp
      in the nasopharynx and performed anterior rhinoscopy using an ordinary speculum.
      However, it was only Voltolini who noticed the transillumination of the maxillary
      sinuses when the lamp was placed in the oral cavity. On October 29, 1888, in
      Breslau he demonstrated diaphanoscopy of the maxillary sinus for the first time.
      Cozzolino claimed that he had introduced this technique prior to Voltolini.
      Voltolini had died in 1889 and could not comment on this. A careful study of the
      original publications, however, shows that Cozzolino had only inspected the nasal
      cavity with retronasal illumination, but had not demonstrated the maxillary sinus
      by transillumination. The diaphanoscopy of the paranal sinuses was very soon
      elaborated to perfection: Vohse in 1890 applied it to the frontal sinuses, Gerber
      in 1900 invented a double diaphanoscope for examining both frontal sinuses
      simultaneously. Although the shortcomings of diaphanoscopy soon became apparent,
      the method was widely used for about half a century, but in the end could not
      compete with modern techniques of radiography and ultrasound. The history is
      related in detail and illustrated with numerous figures.

PMID- 9644680
TI  - [Restorative interventions of the tympanic membrane and mastoid. II].

PMID- 9644681
TI  - M. D. Anderson initiates aggressive ovarian cancer screening program.

PMID- 9644682
TI  - Chemotherapy may improve quality of life of patients with incurable cancer.

PMID- 9644683
TI  - Extraovarian primary peritoneal carcinoma.
AB  - Extraovarian primary peritoneal carcinoma (EOPPC), a relatively newly defined
      disease that develops only in women, accounts for approximately 10% of cases with
      a presumed diagnosis of ovarian cancer. Characterized by abdominal
      carcinomatosis, uninvolved or minimally involved ovaries, and no identifiable
      primary, EOPPC has been reported following bilateral oophorectomy performed for
      benign disease or prophylaxis. Most cases are of serous histology; however,
      nonserous tumors have been observed. Although EOPPC is similar to serous ovarian
      carcinoma with respect to clinical presentation, histologic appearance, and
      response to chemotherapy, molecular and epidemiologic studies have indicated that
      it may be a separate entity. This review explores the clinical presentation,
      management, prognosis, and survival of EOPPC.

PMID- 9644684
TI  - Salvage therapy for ovarian cancer.
AB  - Patients with epithelial ovarian cancer must receive optimal surgical care and
      state-of-the-art chemotherapy in the primary treatment setting. The salvage
      treatment of women with recurrent or persistent ovarian cancer remains a
      difficult task. A very small percentage of patients with platinum-sensitive,
      small-volume disease appear to achieve prolonged disease-free survival. The
      treatment of patients with larger-volume disease (> 0.5 cm) or platinum-resistant
      disease remains largely palliative. The plethora of available new agents has
      provided the physician with multiple options for salvage chemotherapy. Although
      cure in the salvage setting is not often achieved currently, palliative treatment
      allows many patients to live painfree, productive lives. Candidates for salvage
      therapy may be grouped into one of several categories, which reflect different
      prognoses for response. These categories include refractory disease (defined as
      progressive tumor during primary treatment), persistent disease (a partial
      response to primary therapy followed by elevated tumor markers or clinically
      evident persistent disease), and recurrent disease (initial complete response to
      primary therapy with subsequent relapse). Categorizing patients into these
      categories provides a systematic method for organizing the administration of
      salvage chemotherapy.

PMID- 9644685
TI  - Clinical trials referral resource. Clinical trials of multimodality approaches
      for advanced esophageal cancer.

PMID- 9644686
TI  - The challenge of designing clinical trials for AIDS-related Kaposi's sarcoma.
AB  - Kaposi's sarcoma (KS) is a frequent cause of morbidity and mortality in patients
      with human immunodeficiency virus (HIV) infection. Several characteristics of KS
      pose challenges for the conduct of clinical trials. Kaposi's sarcoma patients
      often have multiple, irregularly shaped lesions, making accurate assessment of
      tumor size difficult. The lesions may have varying degrees of nodularity.
      Involvement of the lung or other visceral organs often consists of multiple
      irregular lesions. Conventional oncology staging systems cannot be applied
      effectively to KS because there is no clear primary lesion. Kaposi's sarcoma is
      affected by the status of the underlying HIV infection, and there are reports of
      KS lesions regressing in response to effective antiretroviral therapy. A system
      for staging and response assessment in KS, developed by the AIDS Clinical Trials
      Group (ACTG), has proven to be a useful tool for the conduct of trials in KS. A
      newer system that also attempts to assess patient benefit in response to therapy
      is now being developed by the National Cancer Institute, FDA, and AIDS Malignancy
      Consortium. These tools, as well as careful methodology in the conduct of
      clinical trials, should help optimize the clinical development and evaluation of
      new therapies for KS.

PMID- 9644687
TI  - Variations in charges for two major breast cancer surgeries, U.S., 1996.
AB  - In 1996, the total in-hospital charges for the primary treatment of women with
      breast cancer with a modified radical mastectomy averaged $10,000 throughout the
      United States. The total charge (hospital plus physician's fees) varied by 95%
      between the high charge reported in New York ($12,690) and the low charge in
      Michigan ($6,510). The hospital portion of the bill averaged 65% of the total and
      ranged from 51% in New York to 74% in Virginia. The average length of stay for
      these women was 2.39 days and ranged from 3.18 days in New York to 1.69 and 1.66
      days in Washington and Arizona, respectively. The average charge for a partial
      mastectomy was $8,760, with notable variations between states. The Texas total
      charge was the highest ($12,890, some 47% above the US norm) and more than twice
      the low charge in Ohio ($6,080, 31% below the US average). The physicians'
      charges averaged $3,330 for the country as a whole and accounted for 38% of the
      bill. This proportion ranged from 46% of the total in New York to 70% in Indiana
      and Colorado. The average length of hospitalization for a partial mastectomy was
      1.84 days. On average, women remained in the hospital for the longest time in New
      Jersey (2.78 days) and for the shortest time in Oregon and Massachusetts (1.40
      days and 1.45 days, respectively).

PMID- 9644688
TI  - Stereotactic breast biopsy: indications and results.
AB  - Imaging-guided breast biopsy performed with large-core needles can accurately
      diagnose most breast pathologies, often allowing a diagnosis to be made more
      quickly and less expensively than with surgical biopsy. Major complications, such
      as hemorrhage and infection, are extremely rare, although post-biopsy ecchymosis
      and tenderness are not unusual. Because less tissue is removed, post-biopsy
      cosmetic deformity does not occur. Stereotactic biopsy is performed by
      triangulating the position of a breast lesion and by obtaining views angled
      equally off a central axis. This can be done using dedicated tables or add-on
      equipment. Stereotactic core biopsy has a reported accuracy of at least 90%. All
      lesions for which biopsy would ordinarily be recommended are amenable to
      stereotactic techniques, but those near the chest wall or in the axilla may be
      more difficult to biopsy with some equipment. Lesions characterized by
      calcifications are sometimes more difficult to sample. A biopsy diagnosis of
      ductal atypia, because of its histologic heterogeneity, requires surgical
      excision to exclude coexistent carcinoma, which has been found in half of women
      at subsequent surgical excision. A core biopsy diagnosis of ductal carcinoma in
      situ does not preclude the discovery of invasive carcinoma at surgery. In rare
      instances, the small tissue volume removed at stereotactic biopsy does not permit
      a final diagnosis to be made; this occurs most commonly when differentiating
      phyllodes tumor from fibroadenoma.

PMID- 9644689
TI  - Local excision for rectal cancer: an uncertain future.
AB  - Adenocarcinoma of the rectum remains a significant public health challenge, with
      39,000 new cases and 8,500 deaths predicted for 1998. Radical surgery, the
      current standard therapy, frequently necessitates the formation of a permanent
      colostomy and is associated with significant morbidity. For these reasons,
      alternatives to radical surgery have been sought. This review focuses on
      sphincter-sparing surgical modalities for distal rectal cancer. An extensive
      review of the literature on local excision alone, local excision plus
      postoperative radiation therapy (with or without chemotherapy), and local
      excision following preoperative chemoradiotherapy is presented. The design and
      interim results of the sole prospective multi-institution trial of local
      excision, Cancer and Leukemia Group B trial 8984, are also summarized. The
      literature on this subject, which is dominated by single-institution,
      retrospective reports, fails to support local excision as a superior or equal
      therapy to radical surgical excision for invasive distal rectal adenocarcinoma.
      The crucial question regarding the efficacy of radical surgical salvage for local
      recurrence following local excision also remains unanswered. We conclude that the
      role of local excision for invasive distal rectal adenocarcinoma remains
      undefined. If there is a future for this therapeutic modality, it will depend
      significantly on rigorous patient selection, provided that the efficacy of
      radical surgical salvage for local recurrence can be established.

PMID- 9644690
TI  - Remembering not to forget.

PMID- 9644691
TI  - Cancer pain management.

PMID- 9644692
TI  - Medical oncology services in the nonacute setting.

PMID- 9644693
TI  - Developing an oncology internship program.

PMID- 9644694
TI  - Use of scopolamine to improve care of patients who are terminally ill.

PMID- 9644695
TI  - Hospital-wide education on venous access devices.

PMID- 9644696
TI  - Elimination of frequent vital sign monitoring in patients receiving paclitaxel.

PMID- 9644697
TI  - Bereavement program helps to meet families' needs.

PMID- 9644698
TI  - Success in starting peripheral lines.

PMID- 9644699
TI  - Beyond body image: the experience of breast cancer.
AB  - PURPOSE/OBJECTIVES: To describe the mental and emotional impact of treatment for
      breast cancer with a focus on the ways the body is experienced. DESIGN:
      Phenomenologic, descriptive, and interpretive. SETTING: An outpatient treatment
      area of a comprehensive cancer center in the southwestern United States. SAMPLE:
      20 women, ages 20-68 (mean = 50 years), who had mastectomies (including both
      modified radical mastectomies and lumpectomies, with some having reconstruction)
      for breast cancer. METHODS: Content analysis of verbatim transcriptions of open
      ended interviews using hermeneutic phenomenology and descriptive and interpretive
      presentation of a paradigm case. MAIN RESEARCH VARIABLES: Reaction to breast
      cancer and its treatment. FINDINGS: Informants' descriptions demonstrate that the
      body can be viewed as having three aspects: (a) the body as symbol or social
      expression (i.e., how bodies make a social statement and tell others who you
      are); (b) the body as a way of being in the world, including sensations and
      symptoms such as nausea, fatigue, and pain; and (c) the existential sense that
      one needs a body to be in the world (i.e., the body expresses existence), which
      led to more awareness of the possibility of death. CONCLUSIONS: Women treated for
      breast cancer view their bodies in ways that go beyond what is suggested by the
      literature on body image and breast cancer, encompassing a wide range of
      responses. IMPLICATIONS FOR NURSING PRACTICE: The contribution of this study is
      the documentation of the complexity of the meaning of "body" for women with
      breast cancer. Appropriate interventions differ for each aspect of the body: for
      the body as social symbol, programs such as Look Good ... Feel Better or image
      centers; for the body's sensations and symptoms, information about what to expect
      and about symptom prevention and management; for the existential body, active
      listening to fears and concerns and providing assistance as needed.

PMID- 9644700
TI  - Osteoporosis: a concern for cancer survivors.
AB  - PURPOSE/OBJECTIVES: To describe the risk factors, prevention, diagnosis,
      management, and impact of osteoporosis on the lives of women who have survived
      breast and endometrial cancer. DATA SOURCES: Journal articles, selected
      textbooks, prescribing information, and conference proceedings. DATA SYNTHESIS:
      Women who have not been able to have estrogen-replacement therapy (including
      women who have survived breast and endometrial cancer) are at higher risk for
      developing osteoporosis. Osteoporosis is associated with significant medical
      costs and can have a detrimental effect on long-term quality of life (QOL) as
      well as increased mortality. Recently, significant advances have been made in the
      ability to detect and manage osteoporosis. CONCLUSIONS: Thorough assessment,
      appropriate evaluation, and treatment of osteoporosis can reduce the
      complications of this condition and ultimately improve the QOL for women
      surviving cancer. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses should
      include assessment of risk for osteoporosis into their practice. Education about
      the prevention of osteoporosis should be included with other wellness education.
      Women at higher risk for the development of osteoporosis should be referred for a
      diagnostic evaluation. Oncology nurses can provide women with osteoporosis with
      education about treatment as well as psychosocial support.

PMID- 9644701
TI  - Cancer-related diarrhea: a neglected cause of cancer-related symptom distress.

PMID- 9644702
TI  - Cancer-related diarrhea: selected findings of a national survey of oncology nurse
      experiences.
AB  - PURPOSE/OBJECTIVES: To describe oncology nurse experiences with disease- and
      treatment-related diarrhea in patients with cancer, including assessment methods
      and pharmacologic/supportive care. DESIGN: Descriptive. SAMPLE/SETTING: 1,288
      (26%) of 5,000 randomly selected Oncology Nursing Society members employed full
      time in adult clinical settings in the United States. METHODS: Mailed survey with
      scannable booklets. MAIN RESEARCH VARIABLES: Nurse perceptions of disease and
      treatment-related issues associated with diarrhea in patients with cancer, along
      with currently used assessment criteria and nursing care. FINDINGS: Nurses in
      this sample routinely encounter diarrhea in their patients with cancer. They
      commonly assess/document diarrhea by noting its presence or absence, with a
      minority of nurses using a rating tool. When indicated, most nurses prepare
      patients for probable diarrhea. This preparation includes both verbal and written
      instructions about diet, skin care, drug therapy, and treatment of severe
      diarrhea. Nurses report that primary drug therapy for diarrhea consists of over
      the-counter agents. Supportive care consists of fluid/electrolyte replacement,
      skin care and diet modifications, and also bowel rest and parenteral nutrition
      for severe diarrhea. For these nurses, the most important factors influencing
      choice of management strategies are symptom relief and physician and patient
      preference. CONCLUSIONS: Although the majority of nurses in this study report
      providing anticipatory guidance, patient education, and supportive diarrhea
      management, they are not assessing diarrhea systematically. They report common
      use of nonprescription medications, with pharmacologic interventions varying with
      severity of diarrhea. IMPLICATIONS FOR NURSING PRACTICE: Targeted education is
      needed to help nurses implement systematic assessment and documentation. Efficacy
      of diarrhea-management strategies and protocols must be tested-specifically,
      optimal timing and types of skin care, dietary changes, and bowel rest.

PMID- 9644703
TI  - Octreotide in the management of diarrhea induced by graft versus host disease.
AB  - PURPOSE/OBJECTIVES: To evaluate the potential benefit of the somatostatin
      analogue, octreotide, for the management of diarrhea induced by graft versus host
      disease (GVHD). DATA SOURCE: Pilot clinical trial involving 21 patients
      undergoing allogeneic transplant with positive histologic or radiographic
      evidence of GVHD of the gastrointestinal tract who failed antidiarrheal therapy
      with loperamide. DATA SYNTHESIS: A complete response, defined as resolution of
      diarrhea, was seen in 71% of trial participants (15 of 21 patients). At the dose
      and scheduling used (500 mcg i.v. three times daily for a median of seven
      consecutive days), octreotide was extremely well tolerated in all patients.
      CONCLUSIONS: In this pilot study, octreotide treatment was effective in reducing
      the amount of diarrhea in patients with acute GVHD. The data suggest that
      patients receiving octreotide early in the course of the diarrhea experienced
      more benefit than patients with persistent diarrhea prior to receiving
      octreotide. The demonstrated safety and efficacy of octreotide in this patient
      population support further investigation of this therapeutic strategy for GVHD
      induced diarrhea. A randomized, controlled, clinical trial of octreotide versus
      loperamide for the initial treatment of GVHD-induced diarrhea is warranted.
      IMPLICATIONS FOR NURSING PRACTICE: Octreotide should be administered early in the
      course of GVHD as soon as onset of diarrhea is noted and should be discontinued
      as soon as diarrhea resolves to avoid constipation and the potential development
      of an ileus. Because response to the drug usually occurs quickly, maintaining
      treatment for additional days or weeks is unnecessary. If a benefit is not seen
      in four to seven days, continuing octreotide therapy is neither cost-effective
      nor prudent.

PMID- 9644704
TI  - The nurse's role in diarrhea management.
AB  - PURPOSE/OBJECTIVES: To discuss the causes, clinical manifestations, and
      consequences of diarrhea in the patient with cancer; to describe the oncology
      nurse's role in the assessment, management, and treatment of cancer-related
      diarrhea. DATA SOURCES: Synthesis of published peer-reviewed data, professional
      experience. DATA SYNTHESIS: The many causes of cancer-related diarrhea include
      specific types of cancer and specific anticancer treatment regimens (e.g.,
      chemotherapy, radiotherapy). Poorly controlled diarrhea may result in a range of
      physiologic and psychological effects that extend beyond the patient to
      significant others and caregivers. Comprehensive assessment of diarrhea is the
      foundation for the appropriate use of pharmacologic and supportive therapies.
      CONCLUSIONS: Diarrhea, much like fatigue, is a symptom that only recently has
      become a focus of oncology nursing research and focused intervention.
      IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses can significantly influence
      the quality of care given to patients who develop diarrhea as a symptom of cancer
      or as a sequela of cancer therapy. As such, oncology nurses are challenged to
      maintain current knowledge of the causes and available treatment strategies for
      cancer-related diarrhea. Nurses need to rely on their experiential skill and a
      working knowledge of published research to identify patients at risk. They also
      must communicate effectively with patients and caregivers in every practice
      setting about the nature of diarrhea and its causes, as well as develop
      appropriate interventions for each individual.

PMID- 9644705
TI  - Quality of life in breast cancer survivors: implications for developing support
      services.
AB  - PURPOSE/OBJECTIVES: Quality of life (QOL) is becoming more important in regard to
      breast cancer as treatment advances extend the period of survivorship. The
      purpose of this article is to share the results of a cancer center's attempt to
      evaluate the QOL needs of breast cancer survivors in order to provide improved
      supportive-care services. DESIGN: Descriptive mailed survey. SETTING: A medical
      center in southern California. SAMPLE: A random sample of breast cancer survivors
      (N = 298). METHODS: Breast cancer survivors completed a mailed survey that
      included major outcome variables of QOL and pain. Subjects were stratified by
      three age groups: younger than 40 years, 40-60 years, and older than 60 years.
      MAIN RESEARCH VARIABLES: QOL subscales (physical, psychological, social, and
      spiritual well-being) and overall QOL score and pain as assessed by the Brief
      Pain Inventory. FINDINGS: Results indicated continued physical demands of breast
      cancer, including fatigue and pain, as well as psychological burdens related to
      fear of breast cancer recurrence and anxiety. The social well-being domain
      indicated some unique aspects of QOL when applied to breast cancer survivorship
      such as the fear of breast cancer in female relatives. The spiritual well-being
      domain illustrated the unique QOL aspects of life-threatening illness such as
      living with uncertainty and maintaining hope. Breast cancer survivors also
      reported positive aspects and life changes after successfully facing breast
      cancer. CONCLUSIONS: Breast cancer survivors experience many demands of illness
      across the physical, psychological, social, and spiritual domains. IMPLICATIONS
      FOR NURSING PRACTICE: The study's findings can be useful in directing cancer
      centers' efforts to provide comprehensive care for breast cancer survivors.
      Nurses play a critical role in leading these efforts for supportive-care services
      intended to improve the QOL of breast cancer survivors.

PMID- 9644706
TI  - The effectiveness of a nurse-managed minimal smoking-cessation intervention among
      hospitalized patients with cancer.
AB  - PURPOSE/OBJECTIVES: To determine the effectiveness of a nurse-managed minimal
      smoking-cessation intervention among hospitalized patients with cancer. DESIGN:
      Prospective, two-group, randomized clinical trial. SETTING: Urban, academic,
      tertiary-care setting. SAMPLE: 28 adult male and female smokers with a diagnosis
      of cancer who are hospitalized for a surgical procedure. METHODS: During
      hospitalization, subjects were assigned to a minimal smoking-cessation
      intervention group (n = 14) or a usual care group (n = 14). Verification of
      smoking status was performed at a clinic visit six weeks postintervention.
      Nonsmoking status was defined as self-report of zero cigarettes/day during the
      prior week and confirmed by saliva cotinine analysis. MAIN RESEARCH VARIABLES:
      One-time, Inpatient, nurse-managed, minimal smoking-cessation intervention, self
      reported smoking status, and saliva cotinine level of < or = 14 ng/ml. FINDINGS:
      Upon hospital admission, 64% of the intervention group and 71% of the usual care
      group reported their intention to quit smoking. At six weeks postintervention,
      only 21% and 14% of the intervention and usual care group, respectively, were
      classified as abstinent from smoking. More than 90% of the intervention group
      members who resumed smoking did so within first week of discharge. IMPLICATIONS
      FOR NURSING PRACTICE: A more intensive intervention may be necessary to assist
      hospitalized surgical patients in achieving smoking cessation. Additional contact
      prior to discharge or within the first few days postdischarge may be necessary to
      reinforce strategies for remaining abstinent.

PMID- 9644707
TI  - Changing i.v. administration sets: is 48 versus 24 hours safe for neutropenic
      patients with cancer?
AB  - PURPOSE/OBJECTIVES: To examine the effects of changing i.v. administration sets
      at 48 versus 24 hours on the incidence of infusion-related septicemia in
      neutropenic patients with cancer. DESIGN: Prospective, randomized clinical trial
      with repeated measures. SETTING: Large urban cancer center. SAMPLE: 50 adult
      inpatients with a primary diagnosis of hematologic malignancy, breast cancer, or
      testicular cancer or who were receiving a stem cell transplant. METHOD: Subjects
      were assigned randomly to have their i.v. sets changed every 48 or 24 hours.
      Subjects continued in the study for a maximum of five measurements, until they
      were no longer neutropenic, or until transferred or discharged from the hospital.
      MAIN RESEARCH VARIABLES: Rates of infusate colonization, microorganisms
      identified, incidence of infusion-related septicemia. FINDINGS: Colonized
      infusate was detected in 18 (5%) of 413 i.v. sets; 9 (5%) of 177 sets were
      changed at 48 hours, and 9 (4%) of 236 sets were changed at 24 hours (p > 0.05).
      A trend toward increased colonization of i.v. sets used to administer parenteral
      nutrition (19%) and, to a lesser extent, electrolytes (9%) was identified in the
      48-hour group. Coagulase-negative staphylococci were the most frequently isolated
      microorganisms in the i.v. infusate. Similar organisms were isolated from blood
      cultures and administration sets, however, no subject had identical organisms
      isolated from both i.v. infusate and blood cultures. No subject with colonized
      infusate developed infusion-related septicemia. CONCLUSIONS: No difference
      existed in the incidence of colonization or infusion-related septicemia between
      subjects whose i.v. administration sets were changed at 48 versus 24 hours.
      IMPLICATIONS FOR NURSING PRACTICE: Changing i.v. administration sets every 48
      hours is recommended. Exceptions to this include i.v. administration sets used to
      administer blood products and total parenteral nutrition.

PMID- 9644708
TI  - Differences in fatigue by treatment methods in women with breast cancer.
AB  - PURPOSE/OBJECTIVES: To investigate the differences between various cancer
      therapies (radiation, hormonal, chemotherapy, and their combinations) and the
      specific dimensions of fatigue (affective meaning, behavioral/severity,
      cognitive/mood, and sensory). DESIGN: Descriptive, cross-sectional, mailed survey
      design. SAMPLE AND SETTING: Data were collected from women who were breast cancer
      survivors and members of a nonprofit educational organization in the North-east.
      Criteria for this study included no self-reported disease recurrence, and
      treatment was within 18 months prior to the mailed survey (N = 322). The typical
      participant was middle-aged (mean = 52.2; SD = 10.3), Caucasian (93%),
      postmenopausal (55%), and diagnosed with cancer 2.42 (SD = 2.6) years prior to
      the study. METHODS: Secondary data analysis from a study using the Piper Fatigue
      Scale. VARIABLES: Level of fatigue. FINDINGS: Significant differences were found
      by treatment in total fatigue scores (p < 0.03) and cognitive/mood scores (p <
      0.05). Women who received combination therapy had the highest fatigue scores
      (mean = 4.8; SD = 2.0); those who received only radiation therapy had the lowest
      fatigue scores (mean = 2.7; SD = 2.0). CONCLUSIONS: Fatigue in breast cancer
      survivors varies by type of cancer therapy. Future studies are needed to
      investigate the relationships between fatigue and hormonal therapy, and they need
      to be designed to examine changes over time. IMPLICATIONS FOR NURSING PRACTICE:
      Study findings advance knowledge about fatigue in women with breast cancer and
      aid nurses in providing anticipatory guidance for women undergoing different
      treatment regimens.

PMID- 9644709
TI  - Patient management strategies for interferon alfa-2b as adjuvant therapy of high
      risk melanoma.
AB  - PURPOSE/OBJECTIVES: To review results of Eastern Cooperative Oncology Group
      (ECOG) trial E1684 in the context of nursing issues concerning interferon alfa-2b
      (IFN alpha-2b) as adjuvant therapy for high-risk melanoma. DATA SOURCES:
      Published results of ECOG trial E1684 and additional safety data provided by the
      trial sponsor. Selection of material was based on information that would expand
      on published safety results and present patient-management strategies relevant to
      oncology nurses. DATA SYNTHESIS: High-dose IFN alpha-2b significantly prolonged
      median relapse-free survival (< 0.01) and overall survival (p = 0.047), but side
      effects required extensive nursing interventions. With appropriate patient
      management, including dose modifications, 74% of patients who did not relapse
      received a full course of therapy. CONCLUSIONS: Adjuvant, high-dose IFN alpha-2b
      can significantly prolong relapse-free and overall survival in patients with high
      risk melanoma, but nursing interventions are required to ensure patient
      compliance. IMPLICATIONS FOR NURSING PRACTICE: Accurate nursing assessment and
      appropriate interventions can help patients safely complete this effective
      adjuvant therapy.

PMID- 9644710
TI  - [Effect of immobilization on yeast metabolism].
AB  - Respiratory quotients and enzyme activity were determined in yeast cultures of
      Saccharomyces cerevisiae and Kluyveromyces sp., both suspended and immobilized on
      acrylonitrile fibers. Immobilization induced changes in the cell metabolism
      resulting in activation of the basic metabolic pathway of the given type of yeast
      cells.

PMID- 9644711
TI  - [Biosynthesis and isolation of a recombinant protein for producing genetically
      engineered human proinsulin].
AB  - Isolation of the recombinant protein from a genetically engineered Escherichia
      coli 1854 producer for further chemical enzymatic transformation into human
      insulin through proinsulin was studied. Under optimal conditions, the recombinant
      protein formation was more than 35% of the total cell proteins. Structures of the
      polypeptides obtained and purified chromatographically were confirmed by amino
      acid analysis. Human proinsulin was derived from the recombinant protein
      isolated.

PMID- 9644712
TI  - [Stimulating effect of triphenylmethane series dyes on growth of Escherichia coli
      bacteria].
AB  - The stimulating effect of a dye of the triphenylmethane group (fast green)
      applied at low concentrations (10(-4)%) in the presence of toluene on the
      specific growth rate of bacteria was found. The cell size did not change during
      batch cultivation. However, the cell dry weight and zeta-potential increased
      sharply.

PMID- 9644713
TI  - [Potentiometric electrodes for determining choline, butyrylcholine and
      cholinesterase inhibitors].
AB  - Potentiometric choline electrodes were developed on the basis of the mediator
      free bioelectrocatalysis. The electrodes made of a composite carbon-polymer
      material contain choline oxidase and peroxidase coimmobilized on the surface of
      the electrode. The rate of the potential increase was shown to be proportional to
      the choline concentration within a broad range of variation. Coupling of choline
      sensitive electrodes with butyrylcholinesterase makes possible both the direct
      detection of butyrylcholine and analysis of butyrylcholinesterase inhibitors.

PMID- 9644714
TI  - In vitro effect of bacterial lipopolysaccharide on the cytotoxicity of human
      natural killer cells.
AB  - Preincubation with a number of mediators of infection, such as Gram negative
      bacteria (S. typhi), bacterial lipopolysaccharide (LPS), tumor necrotic factor
      alpha (TNF-alpha), and interleukin-2 (IL-2), significantly increases natural
      killer (NK) cell activity in samples of human peripheral blood mononuclear cells
      (PBMC), without changing the levels of either the phenotypic CD16/56 or
      stimulatory CD25 marker. We now report similar results after preincubation of
      highly purified NK cell preparations (CD16 + 56 > 95%; the rest corresponding to
      CD3+ T-cells) with either S. typhi, TNF-alpha or IL-2. However, in similar
      experiments, LPS inhibits, in a dose-dependent manner (final conc. 2.5, 5.0 or
      10.0 micrograms/mL), NK cell cytotoxicity against K-562 tumor cells.
      Preincubation of purified NK cells with LPS (25 micrograms/mL; 10 and 30 min)
      produced significant alterations in the tyrosine
      phosphorylation/dephosphorylation pattern of several intracellular proteins,
      including a significant increase (10 min) in the phosphorylation of the 120; 100;
      72 and 59 kDa proteins, followed (30 min) by the essentially complete
      desphosphorylation of the p59 protein. Qualitatively similar results were
      obtained at lower LPS concentrations e.g., range 2.5 to 20 micrograms/mL. The
      absence of phosphoproteins in the 40-44 kDa range, known to be present after
      incubation of monocytes with LPS, raises the possibility that these "class" of
      proteins may be critical in explaining the LPS inhibitory effect on NK lytic
      function. Our finding may contribute to a better understanding of the mechanisms
      involved in the complex in vivo interaction between LPS, monocytes and NK cells.

PMID- 9644715
TI  - Steroid hydroxylation by human fetal CYP3A7 and human NADPH-cytochrome P450
      reductase coexpressed in insect cells using baculovirus.
AB  - Human fetal CYP3A7 and human NADPH-cytochrome P450 reductase were coexpressed in
      insect cells, TN-5, infected with a recombinant baculovirus carrying both cDNAs.
      The expression of reductase in TN-5 cells was shown to be sufficient for the
      CYP3A7 dependent 16 alpha-hydroxylation of dehydroepiandrosterone. However, the
      extra addition of cytochrome b5 and phospholipid was necessary to obtain a
      maximal activity of CYP3A7 catalyzing the reaction. CYP3A7 expressed in TN-5
      cells was capable of metabolizing testosterone, cortisol and
      dehydroepiandrosterone 3-sulfate as well as dehydroepiandrosterone. The apparent
      Vmax for 6 beta-hydroxylations of testosterone was similar to that obtained for 6
      beta-hydroxylation of cortisol (2.9 versus 2.5 nmol/nmolP450/min). In contrast,
      the apparent Vmax for 16 alpha-hydroxylation of dehydroepiandrosterone and its 3
      sulfate were 20 and 2 times greater than those observed for steroid 6 beta
      hydroxylations, respectively (67.5 and 5.8 versus 2.5-2.9 nmol/nmol P450/min). On
      the other hand, the apparent K(m) for 6 beta-hydroxylations of testosterone and
      cortisol were greater than those for 16 alpha-hydroxylations (120 and 860 versus
      46-58 microM). Thus, CYP3A7 was active for steroid 6 beta-hydroxylations and 16
      alpha-hydroxylations, but there were greater differences in Vmax/K(m) ratios
      between these reactions.

PMID- 9644716
TI  - Pharmacokinetics of a chemoprotective agent, 2-(allylthio)pyrazine, after
      intravenous administration to rabbits.
AB  - The pharmacokinetics of 2-(allylthio)pyrazine (2-AP) were evaluated after
      intravenous administrations of the drug to rabbits. The reason for the multiple
      peaks in the plasma concentration of 2-AP after intravenous administration of the
      drug to rabbits were also investigated. After intravenous administration of 2-AP,
      10, 20, and 50 mg/kg, to rabbits, the pharmacokinetic parameters of 2-AP, such as
      the total area under the plasma concentration-time curve from time 0 to 12 h
      (261, 672, and 1190 micrograms min/ml), the total body clearance (38.3, 42.0,
      44.6 ml/min/kg), and the percentages of intravenous dose of 2-AP excreted in 24 h
      as unchanged drug (0.0306, 0.0252, and 0.0492%), were independent of the dose
      ranges studied. Since the amount of 2-AP excreted in 12-h bile as unchanged drug
      after intravenous administration of 2-AP, 20 mg/kg, was only 0.0241 +/- 0.00156%,
      and some of 2-AP excreted in gastrointestinal tract as unchanged drug was
      reabsorbed, the reason for the appearance of multiple peaks after intravenous
      administration of 2-AP could be at least partly due to gastrointestinal excretion
      of the drug.

PMID- 9644717
TI  - Bioavailability of timolol and aceclidine after ocular instillation in the
      rabbit.
AB  - The bioavailability of timolol and aceclidine after the ocular instillation of
      each drug (timolol 0.5% or aceclidine 2%) or both combined (timolol 0.5% +
      aceclidine 2%) has been evaluated in rabbits. 15 male albino rabbits were treated
      by the instillation of timolol and aceclidine alone or combined in the
      conjunctival sac of the right eye. Timolol concentrations in humor aqueous were
      assayed at 10 min, 30 min, 1 hr, 2 hr, 4 hr and 6 hr after instillation by high
      performance liquid chromatography (HPLC). Aceclidine was assayed by a
      pharmacodynamic method: pupillary diameter at the following time intervals 0
      (basal value), 1 min, 5 min, 30 min, 1 hr, 2 hr, 4 hr, 6 hr after treatment. Our
      results demonstrated that no differences in timolol and aceclidine
      bioavailability were found between simple-drug preparations and their
      combination.

PMID- 9644718
TI  - Intestinal metabolism and transport of alpha-disaccharide conjugates: the role of
      disaccharidase in the Na+/glucose cotransporter-mediated transport.
AB  - Intestinal transport and metabolism of p-nitrophenyl alpha-disaccharides were
      studied. In the absorption of p-nitrophenyl alpha-melibioside, no compounds other
      than p-nitrophenyl alpha-melibioside were detected on either the mucosal or the
      serosal side. In the absorption of p-nitrophenyl alpha-maltoside, on the other
      hand, p-nitrophenyl alpha-glucoside was formed on the mucosal side to appear on
      the serosal side. p-Nitrophenol and p-nitrophenyl beta-glucuronide also appeared
      on the serosal side in the absorption of p-nitrophenyl alpha-maltoside, and the
      total amount transported to the serosal side was significantly decreased in the
      absence of Na+ (a cosubstrate of Na+/glucose cotransporter (SGLT1)). Furthermore,
      the total transport clearance of p-nitrophenyl alpha-glucoside formed from p
      nitrophenyl alpha-maltoside on the mucosal side in the p-nitrophenyl alpha
      maltoside absorption, was similar to that of the absorption of p-nitrophenyl
      alpha-glucoside itself. These results led to the conclusion that the intestinal
      absorption of disaccharide conjugate depended on disaccharidase, and the
      absorption of the alpha-maltose conjugate occurred sequentially by the maltase
      catalyzed hydrolysis of the disaccharide conjugate and SGLT1-mediated transport
      of the glucose conjugate.

PMID- 9644719
TI  - Ameliorative effects of docosahexaenoic acid on serum lipid changes in stroke
      prone spontaneously hypertensive rats.
AB  - It has been shown that docosahexaenoic acid (DHA) has numerous physiological
      actions. However, the precise mechanism of these actions is still obscure, and
      DHA is not yet regarded as a drug. The present study was undertaken to elucidate
      the effects of long-term administration of DHA on the serum lipid concentrations
      in stroke-prone spontaneously hypertensive rats (SPSHR). SPSHR was selected
      because serum lipid derangement is one of the primary risk factors in the
      development and maintenance of hypertension. DHA-treated SPSHR showed
      significantly lower blood pressure when compared with that of non-treated SPSHR;
      total cholesterol, triglyceride, low density lipoprotein and lipid peroxide
      levels were significantly decreased in DHA-treated SPSHR. On the other hand, the
      high density lipoprotein concentrations tended to increase in DHA-treated SPSHR
      when compared with those in non-treated SPSHR. These findings suggest that long
      term administration of DHA has a protective effect against serum lipid
      derangement in SPSHR. This DHA-induced amelioration of serum lipid changes in
      SPSHR might be associated with mechanisms involving the antihypertensive action
      induced by DHA.

PMID- 9644720
TI  - Gastric vascular network in stroke-prone spontaneously hypertensive rats.
AB  - The gastric vascular architecture in stroke-prone spontaneously hypertensive rats
      (SHRSP) was studied three-dimensionally by vascular casting; controls were Wistar
      Kyoto rats (WKY). The vascular network of the gastric mucosa of WKY showed a
      cylindrical shape with regular morphology (honeycomb-like capillary network)
      along the vascular course. In contrast, in SHRSP, an irregular vascular network
      was formed, and arterioles in the gastric mucosa and serous membrane were
      difficult to detect. Aneurysms were also detected in some capillaries in SHRSP.
      We concluded that the development of hypertension may have caused the irregular
      capillary networks in the rat stomach.

PMID- 9644721
TI  - Effect of running training on brown adipose tissue activity in rats: a
      reevaluation.
AB  - The effect was investigated of running training on the thermogenic activity of
      brown adipose tissue (BAT) in rats. The exercised rats were trained on a rodent
      treadmill for 5 days per week and a total of 9 weeks. After the training, a
      significantly lower rate of increase in body weight was found, suggesting some
      training effect, whereas the training failed to induce a decrease in BAT mass. As
      previously reported (Yamashita, Yamamoto et al., 1993), there was also a markedly
      lower expression of uncoupling protein (UCP) mRNA in BAT from trained rats;
      nevertheless, no definite effect of the running training was noted on either UCP
      content or guanosine 5'-diphosphate binding in the mitochondria recovered from
      BAT. The results obtained suggest that running training has no overt effect on
      the thermogenic activity of BAT in rats.

PMID- 9644722
TI  - The effect of gold on zinc in liver and in metallothionein.
AB  - The question as to the increase in Zn and Cu in metallothionein (MT) in response
      to gold (Au) was examined. Each rat was injected intraperitoneally once with 0.9%
      NaCl or Au (5, 10 or 20 mg Au/kg b.w.). The Zn content in livers increased in
      response to Au injection, while the Cu content remained unchanged. After Au
      injection, 40.0-46.3% of the Au contents and 55.0-60.4% of the Zn contents in
      livers were detected in cytosol, respectively. The distribution profiles of the
      hepatic cytosol of Au-injected rats on a Sephadex G-75 column showed that the
      amount of the increased Zn was ascribable to high molecular weight proteins and
      MT. The Zn contents in the MT increased in response to Au injection. There was a
      close relationship between the Zn contents in cytosol and MT. These data
      demonstrated that 68% of the increased Zn in the hepatic cytosol of Au-injected
      rats was bound to MT. These results suggest that the role of MT in Zn
      accumulation in the liver of Au-injected rats was similar to that of MT in Zn
      accumulation in liver of Zn-injected rats.

PMID- 9644723
TI  - Nuclear matrix protein, tumor necrosis factor-alpha, and nitrite/nitrate levels
      in patients with multiple organ dysfunction syndrome.
AB  - Nuclear matrix protein (NMP), an indicator of apoptosis, was analyzed in patients
      with multiple organ dysfunction syndrome (MODS). Blood levels of tumor necrosis
      factor-alpha (TNF-alpha) and nitrite/nitrate (NOx) were also measured in these
      patients to determine the involvement of these factors in the production of NMP.
      Forty-six patients with MODS were studied, 21 (45.7%) of whom died. NMP and TNF
      alpha were measured by enzyme-linked immunosorbent assay (ELISA). NOx was
      measured by the Griess's method. Marshall's multiple organ dysfunction score (MOD
      score) was used as an indicator of organ failure. The severity of organ failure
      was assessed by use of the acute physiology and chronic health evaluation II
      score (APACHE II score). The number of organs that failed was found to be
      significantly correlated with the NMP level. The NMP level was also correlated
      significantly with MOD score and APACHE II score, as well as with TNF-alpha and
      NOx levels. NMP and NOx levels in the group that died significantly exceeded
      those in the surviving group. Results suggest that apoptosis can occur in the
      presence of MODS, and that its extent increases as the number of failing organs
      increases. The results also suggest that TNF-alpha and NO are involved in the
      induction of apoptosis.

PMID- 9644724
TI  - Genistein metabolism in liver microsomes of Wistar and mutant TR(-)-rats.
AB  - In mutant TR(-)-rats lack of the canalicular multispecific organic anion
      transporter prevents the biliary excretion of various phase II conjugates. In
      order to investigate whether this rat strain expresses high amounts of phase-I
      metabolic enzymes to compensate for the deficiency an in vitro study using liver
      microsomes of control and TR(-)-rats was conducted. While liver microsomes of non
      mutant Wistar rats (control) have a higher total cytochrome P450 content, no
      difference is found for NADPH-reductase. Expression of cytochrome P450 (CYP)
      isoforms CYP1A2, 2D, and 2E1 is equal in both rat strains. CYP2B1/2 and 3A1/2,
      however, are significantly impaired in livers of TR(-)-rats. The CYP dependent
      metabolism of genistein (GEN), a widely used inhibitor of the tyrosinekinase, was
      studied in TR(-)- and control rat liver microsomes. Three metabolites (M1-M3)
      were quantified by HPLC, revealing a lower amount of M2 and M3 in TR(-)-rats.
      Phenobarbital-pretreatment increased the formation of M1-M3 in both rat strains
      (2-4 fold). Dexamethasone, a specific inducer of CYP 3A1/A2 in male rats caused
      an even higher induction of M1-M3 (up to 20 fold) particularly in TR(-)-rats
      indicating the involvement of CYP3A isozymes in genistein metabolism. Phase I
      metabolism may compensate for the lack of genistein-glucuronide elimination in
      TR(-)-rats.

PMID- 9644725
TI  - Temperature-dependent lipid peroxidation of rat brain homogenate.
AB  - When rat brain homogenate was incubated without adding iron, lipid peroxidation
      occurred temperature dependently between 27 degrees C and 42 degrees C. When
      homogenates of liver and heart were incubated under the same conditions, lipid
      peroxidation did not occur. The brain, compared with other organs, seems to be
      very vulnerable to oxidative damage with fever. Catalase promoted lipid
      peroxidation. The ability of dihydrolipoic acid and alpha-tocopherol to inhibit
      lipid peroxidation was very weak. In contrast, iron chelators, such as
      bathophenanthroline, desferrioxamine and EDTA, strongly inhibited lipid
      peroxidation, indicating that endogenous iron is involved in lipid peroxidation.
      Dialysis of brain homogenate depressed the temperature-dependent lipid
      peroxidation by about 30%. Then, the iron content of the homogenate decreased by
      about 35%. On the other hand, dialysis of EDTA-treated homogenate completely
      depressed the lipid peroxidation and the iron content of the homogenate decreased
      by about 87%. Adding iron to the homogenate dialyzed after EDTA treatment
      remarkably increased the lipid peroxidation, but the peroxidation reaction
      proceeded temperature independently. Our results suggest that endogenous iron,
      which may bind to cell components, causes temperature dependent lipid
      peroxidation by a site-specific mechanism.

PMID- 9644726
TI  - Nuclear pore changes and absence of apoptosis in lumbar dorsal root ganglion
      neurons of doxorubicin-intoxicated rats.
AB  - Doxorubicin (DXR) produces degeneration of neurons in the lumbar dorsal root
      ganglion (DRG) in rats. Light microscopic studies, which included the terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end
      labeling method, and electron microscopic observation revealed that the moderate
      nuclear and remarkable cytoplasmic degeneration of DRG neurons of Sprague-Dawley
      rats after intravenous administration of 8 mg/kg of DXR was cell necrosis, not
      apoptosis. In some neurons, mostly dark and usually with moderate degrees of
      nuclear degenerative changes, the nuclear pores were decreased in number and
      obscure 14 and 20 days after DXR administration. DXR enters presumably the
      nucleus and is partly removed through the nuclear pores. However, the diameters
      of nuclear pores were similar in DXR-intoxicated and control rats. The changes in
      nuclear pores of neurons in DXR intoxication, which to our knowledge has not been
      previously studied, are considered to be part of the degenerative or necrotic
      changes of DRG neurons.

PMID- 9644727
TI  - Psychological stress and educational effect during bedside practice on
      psychiatric nursing.
AB  - The aim of this study is to analyze the educational effect and the factors of
      psychological stress of bedside practice on psychiatric nursing. The subjects
      studied were 76 nursing students in a nursing college. They answered a
      questionnaire and underwent the STAI-test before and after the periods of their
      bedside practice during psychiatric nursing. The results obtained were as
      follows; 1. The awareness structure of the nursing students was composed of 6
      factors, that is, anxiety and detestation factor, understanding and acceptance
      factor, social alienation factor, denial factor, affirmation factor and closed
      society factor. 2. The changes in their awareness were observed before and after
      the periods of bedside practice. 3. The STAI-test showed that the nursing
      students frequently complained of anxiety before the bedside practice because
      they had only studied about the psychoses. 4. The nursing students who had strong
      anxiety also showed a deep fear and detestation. 5. Some nursing students who had
      had a deep anxiety before the bedside practice found their anxiety reduced
      because of the direct contact with psychotic patients. 6. Although the nursing
      students had psychological stress, they were also interested in the psychiatric
      nursing.

PMID- 9644728
TI  - [Basic life support skills of the first aid course II/standard first aid course
      ambulance personnel].
AB  - This study was undertaken to evaluate thirteen elements of basic life support
      skills of the First Aid Course II/Standard First Aid Course (FAC II/SFAC)
      ambulance personnel and to determine the effects of FAC II/SFAC education and
      basic life support instructor courses. Ninety-eight FAC II/SFAC ambulance
      personnel were enrolled in this study. It was found that only half of the
      personnel possessed the skills required for assessing respiration, mask holding
      and producing adequate tidal volume by the bag-valve-mask devices at the
      acceptable levels. Regarding the effect of the time that had passed following FAC
      II/SFAC education, we did not find any correlation between the time and the
      levels of skills. However, there was a tendency in which the skills for assessing
      mental status/respiration and for manual airway control were less adequately
      possessed by FAC II/SFAC personnel who did not take basic life support instructor
      courses, particularly those who had completed FAC II/SFAC education more than
      four years prior to this study. Since airway control and respiratory management
      play a key role in saving patients in life-threatening conditions, we need to
      critically reevaluate how the initial FAC II/SFAC education and continuing
      education programs can best be implemented.

PMID- 9644729
TI  - A case of pulmonary reaction with skin eruption showing a positive peripheral
      lymphocyte stimulation test result for ethambutol.
AB  - We report a case of an elderly male whose pulmonary reaction with skin eruption
      occurred in the initial phase of chemotherapy composed of isoniazid, rifampicin,
      and ethambutol (EB). A peripheral lymphocyte stimulation test (LST) showed a
      positive reaction only to EB. The blood serum analysis of the patient when this
      reaction occurred revealed an elevated titer of antinuclear antibody. Computed
      tomography (CT) scan films of the chest when the pulmonary reaction occurred
      showed multifocal subpleural consolidations. There has been only one reported
      case of EB-induced pulmonary reaction and its clinical course was very similar to
      ours. However, LST results and computed tomography (CT) scan findings of the
      chest were not documented in that case.

PMID- 9644730
TI  - [Antigen-recognition mechanism of T cells].
AB  - The antigen-recognition mechanism of T cells was reviewed from the standpoint of
      MHC-restriction. T cells recognize antigens presented by antigen-presenting cells
      in a MHC-restricted manner. CD4+ helper T cells recognize antigens with the
      context of MHC class II molecules, and CD8+ cytotoxic T cells recognize antigens
      with MHC class I molecules. The MHC class I molecule is composed of alpha-chain
      and beta 2-microglobulin, and MHC class II molecule is composed of alpha-chain
      and beta-chain. The T cell antigen receptor is composed of alpha-chain and beta
      chain, or gamma-chain and delta-chain, and CD3 complex. Antigens are processed
      and presented by antigen-presenting cells to T cells in the context of MHC
      molecules. Furthermore, costimulatory factors such as adhesion molecules and
      cytokines are required for the full activation of T cells. The biological
      significance of the T cell antigen recognition mechanism is discussed from the
      standpoint of clinical application.

PMID- 9644731
TI  - Physico-chemical characterization of grain dust in storage air of Bangalore.
AB  - An Anderson personal cascade impactor was used to study the particle mass size
      distribution in the storage air of two major grain storage centers in Bangalore.
      Dust levels in storage air as well as the personal exposures of workers were
      determined along with a detailed study on the particle size distribution. Protein
      and carbohydrate content of the dust were also determined respectively in the
      phosphate buffer saline (PBS) and water extracts by using the standard analytical
      techniques. Personal exposures in both of the grain storage centers have been
      found to be much above the limit prescribed by ACGIH (1995-96). But the results
      of particle size analysis showed a higher particle mass distribution in the non
      respirable size range. The mass median diameters (MMD) of the storage air
      particulate of both the centers were found to be beyond the respirable range.
      Presence of protein and carbohydrate in the storage air dust is indicative of the
      existence of glyco-proteins, mostly of membrane origin.

PMID- 9644732
TI  - [Research on the contents of material safety data sheets].
AB  - The Material Safety Data Sheet (MSDS) system for the safe management of chemical
      substances was officially promulgated in 1993 and has been gradually put into
      practice through administrative guidance in Japan. However, little research has
      been done on the quality of such data sheets provided from various sectors of
      industries. We examined two sets of MSDSs obtained from a refractory ceramic
      plant. In the first survey in 1995, the set of MSDSs was from July, 1992 to
      March, 1994; and in the second survey in 1997, the set was from April, 1994 to
      November, 1996. The number of MSDSs examined in these two surveys was 159 and 81,
      respectively. The number of MSDSs in which "Hazard Identification" was indicated
      was 100 (63%) in the 1995 survey and 75 (93%) in the 1997 survey. The number of
      those in which "Toxicological Information (Stability and Reactivity)" was
      indicated was 81 (51%) and 80 (99%), respectively. The description rates for the
      essential items, including the above two, were found to be improving.

PMID- 9644733
TI  - [Rheumatic diseases in the light of international statistic classification of
      diseases and health problems (10th revision)].

PMID- 9644734
TI  - [Selective inhibitors of cyclooxygenase-2: new perspectives of human diseases
      management].

PMID- 9644735
TI  - [Common variable immunodeficiency in adults and problems of its immunotherapy].
AB  - AIM: Clinicoimmunological study of adult patients with prevailing defect of
      humoral immunity, development of diagnostic criteria and treatment of this
      disease. MATERIALS AND METHODS: Clinical, immunological and microbiological
      examinations were made in 68 patients with defects of antibody formation.
      RESULTS: Total variable immunodeficiency (TVID), selective deficiency of IgA,
      congenital agammaglobulinemia, hyper-IgM-syndrome were detected in 74, 13, 10 and
      3% of patients, respectively. TVID was frequently associated with respiratory,
      chronic ENT and gastrointestinal diseases, low CD4+ and high CD8+ levels. The
      response was achieved with combined therapy: antibacterial treatment +
      immunocorrection + differentiated replacement with plasma or immunoglobulins.
      CONCLUSION: In choice of immunotherapy of TVID patients it is necessary to
      consider parameters of immunogram. Intravenous administration of immunoglobulin
      preparations provided the highest effect in good safety.

PMID- 9644736
TI  - [HLA-antigens and some pathogenetic aspects of reactive arthritis].
AB  - AIM: Investigation of associations of reactive arthritis (ReA) with
      histocompatibility antigens class I and II and determination of new approaches to
      assessment of association ReA with antigen HLA B27. MATERIALS AND METHODS: 118
      ReA patients with associated intestinal and 82 ReA patients with associated
      urogenital infection were studied. The infection was identified
      bacteriologically, with agglutination reaction, enzyme immunoassay, direct and
      indirect immunofluorescence, culturing. HLA-antigens were studied in
      lymphocytotoxic test: locus A, B and C in all the patients, DR in 65 patients.
      RESULTS: ReA triggers were intracellularly parasite bacteria: facultative
      parasites in the enterocolitic variant (Yersinia, as a rule), obligate parasite
      in the urogenital (Chlamidia, as a rule). HLA B27 antigen was discovered in 77.5%
      of patients (RR 45.8), HLA DR1--in 48.4% of patients (RR 3.3). In urogenital
      variant HLA B27 antigen occurred more frequently than in enterocolitic: 87.8% (RR
      95.6) versus 70.3% (RR 31.5); p < 0.01). In HLA-B27-positive patients compared to
      HLA-B27-negative ones there were higher ESR (p < 0.001), leukocyte count (p <
      0.05), concentrations of CRP and alpha-2-globulins (p < 0.001). CONCLUSION: In
      HLA-B27-subjects optimal conditions exist for generalization of obligate
      parasites and favorable for production of facultative ones. The degree of
      association of ReA with HLA B27 antigens is dependent on adaptive features of
      microorganisms appearing in the process of evolution--obligaty and
      facultativeness of their internal parasitivity.

PMID- 9644737
TI  - [Conception of direct participation of intestine in pathogenesis of rheumatoid
      arthritis].

PMID- 9644738
TI  - [Neopterin: laboratory marker of cellular immunity activation in rheumatoid
      arthritis].
AB  - AIM: Measurement of neopterin in the serum of patients with rheumatoid arthritis
      (RA). MATERIALS AND METHODS: 59 patients with verified RA diagnosis (22 cases of
      joint lesion stage I-IIa, 27 of stage IIb-IIIa, 10 of stage IIIb-IV established
      roentgenologically, 48 patients were seropositive by IgM-rheumatoid factor) were
      examined for concentrations of serum neopterin and C-reactive protein (CRP). The
      activity and prognostic factors were characterized by modified Wilke method, the
      severity index was calculated. 100 healthy donors served controls. RESULTS:
      Immune inflammation in RA develops with growing neopterin concentration in the
      serum. This concentration well correlates with inflammation activity and
      intensification of systemic symptoms. CONCLUSION: Neopterin measurements may be
      important for determination of inflammation activity in RA. Further efforts
      should be made to ascertain relationships between neopterin hyperproduction and
      disturbances of cellular immunity in RA, clinical value of neopterin assays
      compared to the other laboratory evidence, feasibility of using neopterin levels
      to define prognosis and efficacy of on-going therapy.

PMID- 9644739
TI  - [New approaches to biological immunomodulation therapy of rheumatoid arthritis:
      neutralization of basic cytokines].
AB  - AIM: Investigation of efficacy of antibodies ot interferons in rheumatoid
      arthritis (RA) versus relevant efficacy of the tumor necrosis factor (TNF),
      comparison of the above cytokines in monotherapy and combined treatment.
      MATERIALS AND METHODS: An open controlled randomized trial of clinical benefit
      and tolerance of anticytokine antibodies was performed in a group of RA patients
      at stage II, III and IV (1, 20 and 4 patients, respectively). The activity degree
      II and III was in 10 and 15 patients, respectively. All the patients had
      articular functional insufficiency of the second degree. 21 patients failed
      previous therapy with basic drugs including immunodepressants. RESULTS: The
      anticytokine antibodies proved to be highly effective in RA. Positive changes in
      teh disease activity were achieved early after the end of the 5-day course in 88%
      of patients. The most definite immediate therapeutic effect was noted in usage of
      TNF antibodies both in monotherapy and in combination with other anticytokines.
      Long-term effect was the best in patients given antibodies to interferon gamma.
      Interferon-alpha antibodies produced weaker effect. The combined treatment had no
      advantages over the monotherapy. CONCLUSION: A significant therapeutic effect of
      antibodies to interferon-gamma is indicative of an important role of this
      cytokine in RA pathogenesis. Anticytokine antibodies are promising as a component
      of combined therapy of patients with resistant RA.

PMID- 9644740
TI  - [Criteria of aggressive rheumatoid arthritis course in children].
AB  - AIM: To ascertain criteria of aggressive course of juvenile rheumatoid arthritis
      (JRA) during 6-12 months since the disease onset, to measure the rate of
      destruction progression, to formulate indications for conduction of early
      immunosuppressive therapy. MATERIALS AND METHODS: The study included 30 patients
      (21 girls and 9 boys) aged 4-15 years with classic JRA. 25 children (76.2%) had
      systemic, 5 children--articular disease (23.8%). RESULTS: 50% and 20% of the
      examinees got the disease before they reached the age of 5 years and in puberty,
      respectively. Severe systemic disease in the debute was registered in 83.3% of
      patients, 16.7% developed primarily articular JRA. For 1 year the disease
      transformed into generalized and polyarticular in 43.3% and 56.7% of patients,
      respectively. Its activity reached the third degree in all the patients. IgG
      levels exceeded the age standards 1.5 times. Articular dysfunction occurred in
      100% of the cases. Destruction in the joints was recorded in 37% and 92.5% of
      patients after 1 and 2 years of the disease, respectively. CONCLUSION: Early or
      in prepuberty, puberty onset of JRA, systemic variants of the debute, debute by
      classical seropositive RA without systemic symptoms, fast appearance of
      symmetric, generalized joint lesions, recurrent course with high ESR, C-reactive
      protein, IgG, growing joint functional insufficiency within the first year of the
      disease may severe criteria of aggressive course of RA in children. RESULTS: The
      presence of the above markers in RA patients is indication for administration of
      the disease-controlling drugs within the first 12 months before development of
      anatomic destruction and the patients' invalidation.

PMID- 9644741
TI  - [Significance of antibodies to herpesviridae viruses detectable in rheumatic
      diseases].
AB  - AIM: To assay antibodies to cytomegalovirus (CMV), herpes simplex virus type 1
      and 2 (HSV-1, HSV-2) and Epstein-Barr virus (EBV) in rheumatic patients and to
      clarify clinical correlations. MATERIALS AND METHODS: A total of 66 patients were
      examined: 7, 19, 6, 3, 5, 2 and 24 with rheumatoid arthritis (RA), systemic lupus
      erythematosus (SLE), reactive arthritis (ReA), scleroderma systematica (SS),
      erythema nodosum (EN), hemorrhagic vasculitis (HV), active or chronic viral
      infection (A/CVI), respectively. Clinical, laboratory tests, tests for specific
      IgM- and IgG-antibodies to CMV, HSV-1, HSV-2, EBV, x-ray examinations were
      performed. RESULTS: IgG-antibodies to CMV were detected in 79%, VCA-IgG
      antibodies to EBV in 70.3%, EA-IgG-antibodies to EBV in 56.6%, IgG-antibodies to
      HSV-1 in 42.1% of patients. Active CMV infection was diagnosed in 27.8%, active
      EBV infection in 56.6%, combination of CMV and EBV infection in 46.9% of cases.
      High titers of antibodies to CMV and EBV correlated with such symptoms as fever,
      arthritis, myalgia, carditis, hepatomegalia, migrating erythematous eruption.
      Acute-phase indices were related to high titers of antibodies to CMV and EBV.
      Elevated titers of antibodies to CMV and EBV were registered both in untreated
      patients and in patients treated with corticosteroids, nonsteroid
      antiinflammatory drugs and aminoquinoline drugs. CONCLUSION: In differential
      diagnosis of rheumatic diseases it is necessary to consider possibility of CMV
      and EBV infections. If these are detected, antiviral measures should be taken.

PMID- 9644742
TI  - [Pathogenetic aspects of chlamydia-associated urogenic arthritis: feasibility of
      microorganism reproduction in cells of articular cartilage].
AB  - AIM: The study of feasibility of Chlamydia trachomatis infection and
      reproduction. This microorganism is an essential etiologic factor in urogenic
      arthritis, in chondrocytes and fibroblasts of human skin. MATERIALS AND METHODS:
      Infection of human skin chondrocytes and fibroblasts was made with chlamydia CP-1
      strain isolated from joint fluid of the patient and serially passaged in the
      hen's embryo yolksacs. The inoculation results were assessed by direct staining
      with the use of monoclonal and fluorescent antibodies and hematoxiline. RESULTS:
      Chlamydial infection of human skin connective tissue, chondrocytes of the
      auricular cartilage and fibroblasts in particular, is possible. CONCLUSION: The
      findings confirm the ability of Chlamydia trachomatis to reproduce in the
      cartilage tissue.

PMID- 9644743
TI  - [Antibodies to low density oxidated lipoprotein and ischemic cerebrovascular
      disorders in young patients].
AB  - AIM: The study of the detection rate and potential pathogenetic significance of
      antibodies to low density oxidated lipoprotein (LDOL) in patients who had
      ischemic cerebral circulation disorder (ICCD) at young age. MATERIALS AND
      METHODS: The examination (enzyme immunoassay, general and neurological
      investigations, laboratory and instrumental tests) covered 148 patients who
      survived ICCD at young age (mean age 37.2 years). RESULTS: 48 of 108 (44%)
      patients had LDOL antibodies. Antibodies to cardiolipin, lupus anticoagulant were
      recorded in 33 (31%) patients. LDOL antibodies were higher and occurred more
      frequently in patients with Sneddon's syndrome (35% of patients, mean LDOL
      antibodies-44 units) and primary antiphospholipid syndrome (17% of patients, 45
      units) than in atherosclerotic affection of the major head arteries (4%, 29
      units) or occlusion of cerebral arteries of unclear genesis (8% of patients, 29
      units). CONCLUSION: ICCD were not related to fast development of cerebral
      atherosclerosis or periaortitis due to production of LDOL antibodies as no
      relationships were found between their rise and atherosclerotic lesions of
      cerebral major arteries or periaortitis as shown by ultrasonic dopplerography or
      cerebral angiography. Feasibility of LDOL antibodies participation in the
      coagulation cascade and induction of hypercoagulatory condition causing ICCD
      needs special investigation.

PMID- 9644744
TI  - [Neurovascular syndrome in some rheumatic diseases].
AB  - AIM: Assessment of neuromotor system and suprasegmentary vegetative structures in
      patients with systemic vasculitis (SV), systemic lupus erythematosus (SLE),
      scleroderma systematica (SS) for determination of the vegetative profile and
      pathogenetic links underlying vegetative disorders. MATERIALS AND METHODS: The
      examination of 125 rheumatic patients included clinical, laboratory,
      instrumental, neurological, neuropsychic, electroneuromyographic, vegetologic,
      pathomorphologic and biochemical investigations. RESULTS: Rheumatic patients
      presented affections of the peripheral and central venous systems, vegetative
      dysfunction, disturbed higher nervous activity manifesting as polyneuropathy,
      mononeuropathy, pyramid syndrome, dystonia, hypothalamic syndrome, reduced
      adaptive ability, low tonicity of the sympathetic nervous system, terminal
      branches of the motor axons, etc. CONCLUSION: Therapy of nervous disorders in
      rheumatic patients comprises treatment of cerebral circulation (vascular,
      nootropic drugs, cerebrolysin), asthenic, neurotic and vegetative disorders
      (sedative and vegetotropic drugs, etimisol, adaptogens), abnormalities of
      peripheral nervous system (amiridin, anticholinesterase preparations, vitamins B
      and others). Follow-up and correction of the on-going therapy contribute to a
      decrease in the number of invalidating and lethal neurological complications.

PMID- 9644745
TI  - [Clinical and laboratory characteristics of patients with Sjogren's disease
      lasting from young age].
AB  - AIM: Characterization of Sjogren's disease (SD) with onset at early age basing on
      the comparison of two patient groups--with the disease onset at the age under 30
      and over 50. MATERIALS AND METHODS: Clinical, ophthalmological and stomatological
      examinations were performed in 31 SD patients who developed the disease at the
      age under 30 (group 1) and over 50 (group 2). RESULTS: In group 1 the disease
      started with parotitis in 42.8% of cases, dysfunction of secreting epithelial
      glands was rare, functional activity of exocrine glands was normal,
      dysproteinemia (high total protein levels, hypergammaglobulinemia,
      hypoalbuminemia) and immunological defects (high levels of circulating immune
      complexes, rheumatoid factor, antinuclear factor) were more pronounced. At
      retrospective analysis not only a decline of functional activity of the salivary
      and lacrimal glands but also appearance of systemic symptoms were registered.
      CONCLUSION: Development of systemic SD symptoms at young age necessitates early
      pathogenetic therapy employing corticosteroid, cytostatic and other drugs.

PMID- 9644746
TI  - [Madecassol treatment of systemic and localized scleroderma].
AB  - AIM: The trial of efficacy of 6-month therapy with madecassol (tablets, ointment,
      powder) of patients with systemic and focal scleroderma (SS and FS). MATERIALS
      AND METHODS: 54 patients (49 females and 5 males) aged 15 to 70 years with
      scleroderma running from 3 months to 15 years entered the study. 30 patients had
      typical SS, 24 patients had FS. Tablets were given to 18 patients, ointment was
      applied in 42 patients, powder in 3 and tablets + ointment in 9 patients.
      Madecassol 10 mg tablets were taken 3 times a day by patients with SS and
      advanced FS. The ointment was preferred in ulcers and scars on fingers and toes
      in SS and vascular trophic lesions in FS. In active focal scleroderma the
      ointment was applied to the skin lesions. The ointment was used 2 times a day (in
      the morning and evening) for 1-6 months. Madecassol powder was employed rarely,
      primarily of anal and vulval lesions. RESULTS: 6-month oral course (30 mg/day) in
      12 SS patients brought about a decrease of indurative lesions, hyperpigmentation
      (8), vascular trophic disorders (6) and improvement of general condition (5).
      Subjective response was good in 10 patients and corresponded to absence of
      progression. In progressive disease and diffuse skin lesions the drug was
      ineffective. The best response was obtained in local application of madecassol
      ointment on digital ulcers in SS. CONCLUSION: Madecassol is effective and well
      tolerated and therefore recommended for oral and local use in combined treatment
      of SS adn FS. Indications for per os utelization are: chronic or subchronic SS
      with limited skin involvement, advanced and/or prone to progression FS in which
      combined administration of the tablets and ointment is proposed.

PMID- 9644747
TI  - [Outpatient care of young invalids with locomotor defects].
AB  - AIM: The study of somatic health in patients with locomotor defects (infantile
      cerebral paralysis, meningoencephalocele, myodystrophy) to reveal abnormalities
      in function of the principal systems and organs of these patients. MATERIALS AND
      METHODS: The examination covered 93 students of Moscow institute for invalids
      suffering from locomotor defects (mean age 18.2 +/- 0.1 years). Clinical,
      laboratory, instrumental tests, ultrasound investigation of the viscera and
      heart, gynecological functional tests were made. RESULTS: Defects were found
      almost in all the essential systems of the body in the majority of the invalids.
      The changes revealed were both functional and organic. Relevant correction was
      needed. Affection of the somatic organs impaired adaptation, resulted in still
      worse conditions for learning. Attendant somatic diseases aggravated the
      underlying disease. CONCLUSION: Visceral affections in patients with locomotor
      defects aggravate the underlying disease and provoke more severe disability. Poor
      rehabilitation results lead to defective social adaptation. The authors propose
      introduction of special therapeutic programs for primary and secondary
      prophylaxis of somatic lesions in invalids with locomotor affections. Further
      study of somatic status of invalids is thought valid.

PMID- 9644748
TI  - [Cerebral pathology in inactive rheumatism].
AB  - AIM: Characterization of cerebral pathology in inactive phase of rheumatism.
      MATERIALS AND METHODS: Clinical, experimental psychological examinations were
      performed in 110 rheumatic patients with inactive disease. Computer tomography of
      the head was carried out in 45 patients. RESULTS: Psychic defects were absent
      only in 2.73% of the examinees. The rest had different neurotic symptoms manifest
      as panic attacks (> 50% of cases) or mildpsychoorganic shifts (60.91% of cases).
      Computer tomography of the brain has revealed hypodensive foci, deformed
      subarachnoid spaces and cerebral ventricles, hydrocephalia in 66.67% of the
      patients. These occurred more frequently in patients with psychoorganic syndrome
      or valvular heart diseases. CONCLUSION: Treatment and rehabilitation of rheumatic
      patients should also include measures to correct psychic and cerebral
      abnormalities frequently present in such patients.

PMID- 9644749
TI  - [Changes of lipid metabolism in cardiac failure patients with rheumatic heart
      disease].
AB  - AIM: The study of lipid metabolism parameters involved in lipid mechanisms of
      damage and elucidation of their role in disorders of central hemodynamics (CH),
      microcirculation (MC) and oxygenation (OG) of peripheral tissues in cardiac
      failures (CF) in rheumatic patients. MATERIALS AND METHODS: In 55 patients with
      rheumatic heart disease (RHD) with CF measurements were made of serum
      characteristics of peroxidation-antioxidant balance, activity of phospholipase
      A2, concentration of nonesterifized fatty acids, total lipids, total
      phospholipids, total, ether-bound and free cholesterol, skin OG and MC.
      Tetrapolar chest rheography was followed by calculation CH parameters. RESULTS:
      CF aggravation occurred in parallel with progression of generalized activation of
      lipid peroxidation (LPO) and phospholipase A2. LPO activation contributes to
      inhibition of antioxidant activity and to decline of hypercholetsrolemia.
      Negative correlation exists between primary LPO products, dienic conjugates and
      CH. CONCLUSION: LPO and phospholipase A2 activation are essential in the onset
      and progression of CF in RHD patients. This should be considered in therapy of
      such patients.

PMID- 9644750
TI  - [Comparative efficacy, safety, cardio-hemodynamic effects of isosorbide dinitrate
      (ID) aerosol and sublingual tablets of nitroglycerin].
AB  - AIM: To study efficacy, safety, cardiohemodynamic effects of ID aerosol--isoket-
      for relief of anginal attacks and their prevention in long-term treatment.
      MATERIALS AND METHODS: 15 patients with ischemic heart disease suffering from
      stable angina class II-III. Isoket was tried for efficacy, tolerance, hemodynamic
      parameters, morphofunctional status of the heart, exercise tolerance. RESULTS:
      Isoket aerosol in a dose 1.25 mg as a single oral spray arrested anginal attacks
      in all the patients. In long-term regimens good antianginal effect was achieved
      in 60% of cases. The ID aerosol produces a fast antianginal effect, improves
      morphofunctional cardiac parameters and exercise tolerance. CONCLUSION: Isoket
      spray is effective and safe antianginal drug.

PMID- 9644751
TI  - [Comparative trial of 3-day azithromycin versus 10-day coamoxilav course efficacy
      in acute sinusitis].
AB  - AIM: To investigate the validity of a short-term course of azitromycin in acute
      sinusitis (AS). Comparison of clinical and bacteriological effects, tolerance of
      azitromycin and co-amoxiclav. MATERIALS AND METHODS: 50 AS patients were given a
      single 500 mg daily dose of axitromycin for 3 days and 50 such patients received
      co-amoxiclav 625 mg 3 times a day for 10 days. The examination performed before
      the treatment, 72 hours, 10-12 and 26-30 days after its beginning assessed the
      presence of fever, head ache, pain at palpation at the site of the sinuses
      projection, nasal breathing and discharge. X-ray examination and microbiological
      analysis of the puncture biopsy from the nasal sinuses were conducted before
      treatment and on its day 10-12. RESULTS: On the treatment hour 72 and day 10-12
      azitromycin efficiency was significantly higher than that of co-amoxiclav.
      Recovery on the treatment day 10-12 was registered in 41(82%) and 26(52%)
      patients, improvement--in 6(12%) and 21(42%), no effect--in 3(6%) and 2(4%)
      patients, respectively, for azitromycin and co-amoxiklav. On the treatment days
      26-30, 45 and 43 patients recovered, respectively. The causative agents were
      mainly S.aureus and Str.pyogenes. Eradication of the pathogens in response to
      azitromycin occurred in 29, to co-amoxiclav in 18 patients. The latter caused
      side effects more frequently. CONCLUSION: Azitromycin vs. co-amoxiclav provides
      cure in acute sinusitis for a shorter time, is better tolerated and less toxic.

PMID- 9644752
TI  - [Antibacterial therapy in rheumatology. Current problem status].

PMID- 9644753
TI  - [Wide-field capillaroscopy in diagnosis and differential diagnosis of rheumatic
      diseases].

PMID- 9644754
TI  - [Therapeutic principles in systemic lupus erythematosis with phospholipid
      syndrome].

PMID- 9644755
TI  - [Ataxia and paralysis in meat chickens, as a result of an infection with avian
      encephalomyelitis virus in the breeding flock].
AB  - An outbreak of avian encephalomyelitis (AE) in 7 broiler flocks, with signs of
      ataxia and paralysis is reported. The diagnosis was made by immunofluorescence,
      histopathology and virus isolation. The breeding flock had a temporary drop in
      egg production and reduced hatchability caused by late embryonic mortality. The
      breeding flock had not been vaccinated against AE. The problems were probably
      caused by vertical transmission of AE virus.

PMID- 9644756
TI  - [Risk factors for Salmonella dublin infections on dairy farms].
AB  - A case-control investigation of the risk factors for Salmonella dublin infections
      on 126 dairy farms identified the following variables as being significantly
      associated with infection: standardized farm size and presence of water courses.
      Contrary to expectations, contact with cattle from other farms when the animals
      were turned out to grass was negatively associated with S. dublin infection. The
      purchase of cattle from other farms was a risk factor. There were more infections
      when feed consisted of grass alone than when grass was supplemented with maize or
      grass silage. S. dublin infections were strongly correlated with liver fluke
      infections.

PMID- 9644757
TI  - [Food panel and diet for domestic animals].

PMID- 9644758
TI  - [Splicing factors in oocyte nuclei from human antral follicles].
AB  - Three groups of oocytes in the human antral follicules were previously
      distinguished on the basis of nuclear structures arrangement and 3H-uridine
      incorporation in the oocyte nuclei revealed by ultrastructural and
      autoradiographic research (Parfenov et al., 1984, 1989). These groups can be
      regarded as consecutive states of oocyte development, i. e. active, intermediate
      and inactive ones. The latter is characterized by compactization of nuclear
      structures arranged within a limited nuclear volume. The present study concerns
      the distribution of splicing factors (snRNP and SC35) and p80 coilin in the
      nuclei of oocytes being at either of the three states. Along with transcription
      decreasing in oocyte nuclei, reduction of snRNP and SC35 amounts in the
      karyoplasm was detected. Simultaneously, accumulation of these splicing factors
      occurred in clusters of interchromatin granules (CIG). snRNP and SC35 are
      spatially segregated in CIG. snRNP are located within the fibrillar zones of CIG,
      while SC35 corresponds to the granular component of CIG. CIG are the only
      structures containing splicing factors in the nuclei of oocytes from the human
      antral follicules. These nuclei lack typical coiled bodies (CB). Considerable
      amounts of the marker protein of CB--p80 coilin are revealed in the nucleolus
      like bodies (NLB) of human oocyte nuclei. Contrary to the data obtained on the
      oocytes from the antral follicules of other mammals (Kopecny et al., 1996a,
      1996b) NLB in human oocytes do not contain snRNPs and SC35. The present study
      allows to make the following conclusions: a) splicing factors recruted to the
      sites of transcription in karyoplasm of oocytes are assembled in CIG when
      inactivation of transcription takes place; b) CIG in preovulated human oocytes
      play substantial role in the storage and preservation of splicing factors.

PMID- 9644759
TI  - [Nucleolar apparatus of neurosecretory cells in the hypothalamus of rats of
      different age during acute immobilization stress].
AB  - To determine condition and adaptive capacity of cell nucleoli at ageing, the
      effect of acute immobilization on the hypothalamic neurosecretory cells was
      investigated in young and old male Wistar rats. Using immunohistochemical methods
      and nucleolometry we have shown that: 1) the nuclear volume in all neurosecretory
      cells is increased; 2) the share of cells, containing nucleoli with marginal
      position or multiple nucleoli in the nuclei, displays opposite changes in young
      and in old rats under stress condition. We suppose that adaptive mechanisms are
      different in young and old animals. Although, both kinds of morphological
      reorganization result in the increase in functional activity.

PMID- 9644760
TI  - [Changes in the structure of the nucleus of neocortical neurons during deficiency
      of serotonin and catecholamines].
AB  - The study was taken on Wistar rats using selective neurotoxins 5,7
      dihydroxytriptamine and 6-hydroxydopamine. The reaction of neocortical neurons to
      monoamine depletion was examined. Alterations in chromatin distribution and
      partial nucleolar segregation were detected in cell nuclei of some neurons.
      Peculiar intranuclear inclusions, persisting for a long period, are also found
      out. We propose that detected changes in the nuclear structure are due to
      intracellular adaptive reactions associated with alterations in nuclear
      cytoplasmic transport and protein synthesis.

PMID- 9644761
TI  - [The effect of calcium precipitate of double-stranded RNA on erythropoiesis in
      rats with acute anemia].
AB  - On the model of experimental acute anaemia of rats, induced by injection of
      phenilhydrazine, the influence of calcium precipitate of double-stranded RNA (Ca
      ds-RNA), introduced during the crise of anaemia, on the process of erythron
      restoration, was studied. In the presence of Ca-ds-RNA the number of pro- and
      erythroblasts in fission increases by 1.5 times, compared with "pure" anaemia
      situation, and accordingly there is a marked decrease in the share of microcytes,
      which play an important role in the restoration of cell number, and in the
      erythron recovery after the crise of anaemia. Less pronounced is the influence of
      Ca-ds-RNA on the macrocytosis, which keeps its value in spite of the increase in
      the speed of development and of the number of normocytes after Ca-ds-RNA
      introduction. The mechanism of Ca-ds-RNA inclusion in the system, which controls
      the process of erythropoiesis during anaemia, is discussed. A conclusion is drawn
      that Ca-ds-RNA may directly affect the inductive stage of erythropoiesis,
      stimulating the formation of competent erythroid cells in population of stem
      haemopoiethic cells and their proliferation. Further development of bone marrow
      cells takes place according to the known programme of erythropoiesis whose
      variations are stimulated by the current conditions of its realization, but not
      by the presence of Ca-ds-RNA.

PMID- 9644762
TI  - [Spontaneous reversion of tumor cells as a source of dormant metastases].
AB  - In the present paper we have shown that JB6 and PDV murine skin carcinoma cells,
      as well as previously described sarcoma B6-4 cells, can revert to a nontumor
      phenotype. Revertant carcinoma clones could not grow in soft agar conditions and
      like sarcoma revertants acquired dependence on peptide growth factors, and
      exhibited a reduced expression of c-jun. Spontaneous revertants were shown to be
      instable. They could revert back to a transformed phenotype in 1-5 months of in
      vitro passaging. Being inoculated in syngeneic animals, these transformed cells
      show a recurrence in 2-5 months, similar to that of a dormant metastasis. Thus,
      dormant revertant cells are believed to be included in many tumors of different
      origin. So, spontaneous reversions of tumor cells may play an important role in
      the dormant metastatic process. The cause of these frequent spontaneous transient
      reversions and revertant instability appears to be of epigenetic nature. Causes
      and mechanisms of cell transformations and reversions remain to be clarified.

PMID- 9644763
TI  - [Expression of intermediate filament proteins in MDCK cells cultured in the three
      dimensional gel in the presence of cytokine HGF/SF].
AB  - An immunomorphologic study was made of expression of intermediate filament
      proteins--keratin and vimentin--in the structures formed in branching
      tubulogenesis of Madin-Darby Canine Kidney epithelial cells (MDCK, clone 20),
      cultured in three-dimensional collagen gel in the presence of the "scatter
      factor" (HGF/SF). An improved method of parallel immunostaining of the whole
      branching structures and of their cryostat cross-sections was used. It was shown
      that both the discoid epithelial cells, forming walls of tubules with inner clear
      spaces, and the fibroblast-like cells invading the collagenic gel coexpressed
      keratin and vimentin. Thus, in the studied system of simplified morphogenesis in
      vitro, some conservatism of intermediate filament protein expression was revealed
      which does not respond to changes in cell shape or cell localization.

PMID- 9644764
TI  - [Activity of various energy metabolism enzymes in the rat placenta after
      treatment with acetone].
AB  - In the rat placenta symplastotrophoblast the activity of glucose-6-phosphatase
      increased and that of Mg-adenosine-thriphosphatase and succinate dehydrogenase
      decreased under the influence of joint and separate action of acetone vapour and
      high air humidity. The activity of alkaline phosphatase is oppressed only at high
      humidity or in combination of high humidity and acetone.

PMID- 9644765
TI  - [Karyotypic instability of peripheral blood lymphocytes in cows Bos taurus L.
      infected with bovine leukemia virus].
AB  - Chromosomal aberrations (CAs), sister-chromatid exchanges (SCEs), aneuploidy and
      proliferative potential (PP) were investigated in peripheral blood lymphocytes of
      healthy cows (control group-C), BLV-(bovine leucosis virus)-infected cattle
      without hematological abnormalities (RID--seropositive group (I) and affected
      with leucaemia (lymphocytosis (LC), lymphoma (L)). Nonrandom chromosomal (marker)
      aberrations were not found in the cow group at stage LC. The levels of aneuploidy
      and SCEs increased in the cow group at stage L compared to the cow group at stage
      I. Polyploidy: C--1.9 +/- 0.28, I--3.5 +/- 0.22, LC--6.1 +/- 0.82, L--10.5 +/-
      0.51 (P < 0.01). Hypoploidy (2n = 58): C--3.0 +/- 0.17, I--54 +/- 0.71, LC--12.1
      +/- 0.72, L--14.0 +/- 0.65 (P < 0.01). SCEs: C--3.8 +/- 0.26, I--5.4 +/- 0.15, LC
      -7.2 +/- 0.16, L--9.7 +/- 0.26 (P < 0.01). There are no differences in CAs rates
      and PP between groups of cows at all the observed stages of leucaemic process.
      The obtained results are discussed in terms of cytogenetic aspects of leucaemic
      process in cows.

PMID- 9644766
TI  - [Stabilization by visible light of macromolecular chromatin complexes in the
      presence of ethidium bromide].
AB  - A method of induction of multiple DNA-protein and protein-protein cross-links in
      chromatin of isolated nuclei has been developed. The cross-linking is brought
      about by mutual effect of fluorochrome ethidium bromide (EtBr) and irradiation
      with blue light. Electron microscopic analysis of nuclei isolated in solutions
      with various concentrations of divalent cations, stained with EtBr and irradiated
      with blue light, has demonstrated that the method leads to a selective
      stabilization of macromolecular complexes of chromatin against various treatments
      causing decompactization of native chromatin. Besides that, the stabilization of
      nucleoli and clusters of interchromatin granules takes place. On the other hand,
      the same treatment does not stabilize elementary chromatin fibers (about 30 nm
      thick), and the transition to the nucleosomal fiber occurs after extraction of
      histone H1 with 0.6 M NaCl. Electrophoretic analysis of proteins from control and
      irradiated nuclei shows the basic role of non-histone proteins in the
      stabilization. The data are discussed based on the assumption on the availability
      of some "intermediate" levels of chromatin compaction between 30 nm chromatin
      fiber and mitotic chromosome.

PMID- 9644767
TI  - Ultrasonographer's wrist--an occupational hazard.

PMID- 9644768
TI  - Microcephaly--no small deal.
AB  - Anatomic shortening of the fetal frontal lobe seems to precede microcephaly.
      Brain size determines the size of the calvarium. The report by Pilu and
      colleagues provides a physiological basis for recent anatomical observations made
      regarding microcephaly. Biometry of the frontal lobe of the fetal brain may be a
      valuable tool for the identification of the fetus at risk for microcephaly. A
      thorough investigation of the subtle brain anatomy of the developing fetus is
      necessary in suspicious cases. Prenatal studies have suggested that abnormalities
      of neurocranial architecture occur in approximately two-thirds of cases. Steinlin
      and colleagues found a much higher incidence in children (90%) affected by
      microcephaly. Either the progressive nature of the condition or the improved
      sensitivity of childhood magnetic resonance imaging (used in their study) over
      prenatal ultrasonography for the detection of subtle brain abnormalities may
      account for this difference. However, high-resolution ultrasonographic
      instruments should allow for the detection of many accompanying neuroanatomic
      abnormalities, possibly before the markedly small calvarium is seen. Finally,
      Pilu and colleagues have shown that the underlying conditions that may predispose
      to brain atrophy may be recognizable with Doppler ultrasonography.

PMID- 9644770
TI  - Inter-twin membrane folding in monochorionic pregnancies.
AB  - This study examines the value of assessing inter-twin membrane folding in
      monochorionic twin pregnancies in the prediction of twin-to-twin transfusion
      syndrome. In 83 monochorionic twin pregnancies ultrasound scans were carried out
      at 10-14, 15-17 and 19-21 weeks to investigate folding of the inter-twin membrane
      as an early sonographic feature of inter-twin discrepancy in amniotic fluid
      volume. There were 23 (28%) cases of membrane folding, which was first observed
      in one case at 10-14 weeks, in 21 cases at 15-17 weeks and in another case at 24
      weeks. In 12 (52%) of the 23 cases the pregnancy progressed to severe twin-to
      twin transfusion syndrome and 10 of these were treated by endoscopic laser
      coagulation of the placental vascular anastomoses. In the other 11 cases there
      was a moderate syndrome with large discrepancies in amniotic fluid volume and
      fetal size, persisting throughout pregnancy. In the severe group, five
      pregnancies resulted in live birth of both babies, three in live birth of one and
      intrauterine death of the other twin and in four cases there were no survivors.
      In the moderate group, all babies survived and the inter-twin disparity in birth
      weight was more than 20%. Similarly, all 60 pregnancies with no membrane folding
      resulted in live births. In all three groups there was an increase in inter-twin
      disparity in fetal size with gestation and the greatest inter-twin disparities
      were in those with moderate twin-to-twin transfusion syndrome from as early as
      the 10-14 week scan. These findings demonstrate that folding of the inter-twin
      membrane occurs in about one-quarter of monochorionic twins and in about half of
      these there is subsequent development of severe twin-to-twin transfusion
      syndrome.

PMID- 9644769
TI  - Prenatal diagnosis and outcome of subamniotic hematomas.
AB  - Subamniotic hematomas are classical placental pathological lesions resulting from
      the rupture of chorionic vessels near the cord insertion. Most subamniotic
      hematomas are found after birth and result from excessive traction on the
      umbilical cord at delivery. The development of these lesions has been rarely
      reported in utero. We report here five cases of subamniotic hematomas diagnosed
      by ultrasound between 18 and 30 weeks of gestation. The sonographic features were
      those of a poorly reflective oval-shaped cystic mass overlying the fetal plate of
      the placenta and covered in a thin membrane. In all the cases, a cystic structure
      containing a thrombotic mass arising from the amniotic membrane, which was
      attached to the fetal placental surface, was found after delivery. A high
      maternal serum alpha-fetoprotein level was found retrospectively in the four
      cases for which this information was available. Two pregnancies were complicated
      by slow fetal growth, one by vaginal bleeding and one by polyhydramnios. These
      findings demonstrated that subamniotic hematoma can be accurately diagnosed in
      utero by ultrasound and differentiated from other lesions of the placental
      chorionic plate. The findings also show that, although the lesion is located
      between the chorion and the amnion, it can be associated with fetomaternal
      hemorrhage and with fetal growth restriction.

PMID- 9644771
TI  - Maternal ophthalmic artery Doppler velocimetry in normotensive pregnancies with
      small-for-gestational-age infants.
AB  - Our purpose was to evaluate whether the maternal ophthalmic artery pulsatility
      index in normotensive pregnancies with small-for-gestational-age (SGA) fetuses is
      different from that in normotensive pregnancies with appropriate-for-gestational
      age (AGA) fetuses. The cross-sectional study involved a group of normotensive
      pregnant women at > 34 weeks' gestation; 16 had fetuses that were AGA and 13 had
      fetuses that were SGA. Color and pulsed Doppler ultrasonography was performed in
      the ophthalmic arteries in each case and the pulsatility index and mean velocity
      were calculated. The heart rate and mean arterial blood pressure were also
      recorded. The pulsatility index of the ophthalmic artery (2.04 +/- 0.39) in
      normotensive pregnant women with SGA fetuses was significantly lower than that
      (2.87 +/- 0.64) in normotensive pregnant women with AGA fetuses (p < 0.05). The
      mean velocity (15.0 +/- 2.7 cm/s) in the women with SGA fetuses was significantly
      higher than that (10.2 +/- 2.7 cm/s) in the women with AGA fetuses (p < 0.05).
      There was no significant difference in maternal heart rate or mean arterial blood
      pressure between the groups. These results suggest that vascular resistance in
      the maternal orbital circulation is reduced in pregnancies that are normotensive
      but which are associated with SGA fetuses.

PMID- 9644772
TI  - Ultrasonographic patterns of polycystic ovaries: color Doppler and hormonal
      correlations.
AB  - Ultrasound has been used in the identification of two different morphological
      patterns of polycystic ovaries, namely a peripheral cystic pattern and a general
      cystic pattern. The aim of this study was to evaluate whether patients with the
      peripheral form of polycystic ovaries showed different ovarian and uterine blood
      flow from those with the general form, and to investigate whether there was a
      correlation between the forms and different hormonal parameters. Eighteen
      patients with the general form and 16 patients with the peripheral form of
      polycystic ovary underwent clinical, biochemical, gray-scale and color Doppler
      ultrasonographic evaluation. The parameters analyzed confirmed polycystic ovarian
      syndrome (PCOS) in all patients. Individual levels of plasma luteinizing hormone
      (LH), follicle stimulating hormone (FSH), testosterone, androstenedione and
      estradiol did not differ between the groups. However, there was a significantly
      higher LH/FSH ratio and a greater stromal echodensity in the peripheral cystic
      group than in the general cystic group. Doppler ultrasonography demonstrated
      significantly lower pulsatility index values in the intraovarian arteries of the
      peripheral cystic group and a higher rate of visualization of these arteries than
      in the general cystic group. These findings suggest that, apart from the LH/FSH
      ratio, the different morphological types of polycystic ovary do not reflect
      differences in endocrine profile. The differences in blood flow demonstrated by
      Doppler assessment in each case, however, showed that PCOS does not predetermine
      a single intraovarian blood flow pattern.

PMID- 9644773
TI  - An evaluation of sonohysterography and diagnostic hysteroscopy for the assessment
      of intrauterine pathology.
AB  - The availability of advanced hysteroscopic surgical techniques has changed the
      management of abnormal uterine bleeding. The aim of this study was to evaluate
      the use of transvaginal sonography (TVS), sonohysterography (SH) and diagnostic
      hysteroscopy (DH) for the preoperative assessment of the uterine cavity. The plan
      was to investigate 100 patients with abnormal uterine bleeding despite
      conventional medical treatment. The endpoints were uterine abnormalities detected
      by operative hysteroscopy and histology, and subjective estimates of discomfort
      during TVS and SH. A total of 104 patients (aged 26-79 years) were recruited and
      98 (94%) underwent all three diagnostic procedures. Uterine abnormalities were
      present in 52 patients (53%). There were 25 cases with at least one endometrial
      polyp, 17 with submucous fibroids, seven with endometrial hyperplasia and three
      with an adenocarcinoma. The overall sensitivity of TVS improved after SH from 67
      to 87% and the specificity from 89 to 91%. The positive predictive value
      increased from 88 to 92% and the negative predictive value from 71 to 86%. The
      use of SH also improved the quality of information about the location and size of
      polyps and submucous fibroids. Increased endometrial thickness associated with
      adenocarcinoma was detected in all cases (three of three) by TVS and in four of
      seven cases of hyperplasia (five of seven cases after SH). Most patients reported
      minor discomfort during TVS or SH and no side-effects were apparent. The
      sensitivity of DH was 90% (92% for polyps, 88% for fibroids); two cases with a
      polyp, two with a submucous fibroid and one with endometrial hyperplasia were not
      detected. The use of saline infusion to enhance visualization of the endometrium
      increases the diagnostic accuracy of transvaginal sonography to approach that of
      diagnostic hysteroscopy and also provides some additional information. This
      development has implications for the management of uterine bleeding disorders.

PMID- 9644774
TI  - Ultrasonographic measurement of endometrial thickness during hormonal replacement
      therapy in postmenopausal women.
AB  - The objective of this study was to measure endometrial thickness by transvaginal
      ultrasonography during two regimens of hormonal replacement therapy (HRT) in
      postmenopausal women and to compare these data with endometrial histology.
      Transvaginal ultrasonographic evaluation of endometrial thickness and endometrial
      biopsy were performed in 80 postmenopausal women before and after 6 months of HRT
      (between the 24th and the 28th day of the cycle). The group was randomized so
      that 40 women (Group A) were treated with a continuous sequential regimen
      consisting of 5 micrograms/day of estradiol continuously and 5 mg/day of
      medrogestone from the 17th to the 28th day of the cycle; and 40 women (Group B)
      were given continuous administration of 50 micrograms/day estradiol and 5 mg/day
      medrogestone. Prior to therapy, there was no significant difference in mean
      endometrial thickness between the groups. After 6 months of therapy, endometrial
      thickness was significantly increased in comparison with basal values in both
      groups. The mean value was significantly higher (p < 0.001) in Group A (8.5 +/-
      3.7 mm) than in Group B (3.6 +/- 1.3 mm). In Group A, endometrial thickness was <
      or = 4 mm in 16.7% of patients and < or = 8 mm in 69.5% of patients. In Group B,
      91% of patients had an endometrium of < or = 4 mm. In both groups, the thickness
      of the atrophic endometrium was less than that of the other histological types of
      endometrium (4.1 +/- 0.3 mm for Group A and 3.5 +/- 1.2 mm for Group B). In Group
      A, the difference in mean endometrial thickness between the proliferative and
      secretory endometrium was not statistically significant. In both groups, the
      transvaginal ultrasonographic measurement of endometrial thickness of < or = 4 mm
      had a high sensitivity for detecting atrophic endometrium (83.3% for Group A and
      93.7% for Group B).

PMID- 9644775
TI  - Alternative technique for Nd: YAG laser coagulation in twin-to-twin transfusion
      syndrome with anterior placenta.
AB  - Nd: YAG laser coagulation is used to treat severe twin-to-twin transfusion
      syndrome (TTS). Success of the technique depends on visualization of the
      placenta, the fetal membranes and the targeted vessels, as well as obtaining an
      optimal inclination angle for laser coagulation. In the rare case of an extensive
      anterior placenta, it may be difficult to achieve these conditions using the
      percutaneous approach. Here, we propose an alternative to the percutaneous
      procedure. Modifications involve an open access and the use of a flexible cannula
      and bent scope. An extraplacental area, usually at the fundus, is identified by B
      mode and color Doppler imaging. A mini-laparotomy is made under general
      anesthesia. The viscera are retracted and the cannula is inserted under direct
      view and ultrasound control by the Seldinger technique. The curved fiberscope is
      passed through the flexible cannula, allowing adequate inspection of the
      placenta, and target vessels can be coagulated at an angle close to 90 degrees.
      After the procedure, the uterus is closed primarily to prevent postoperative
      leakage of amniotic fluid or hemorrhage. This technique has been successfully
      used in six patients with TTS and a completely anterior placenta, with a
      gestational age between 18.5 and 22.0 weeks. In all patients, the amniotic cavity
      was accessed without hemorrhage. The outcomes are similar to those published
      previously for laser coagulation. The mean interval from intervention until
      delivery was 10.5 weeks. All 12 fetuses were live born but four died from
      complications of extreme prematurity. No maternal complications occurred.

PMID- 9644776
TI  - The instantaneous measurement of multiple Doppler spectra in the investigation of
      ovarian masses.
AB  - The use of Doppler indices of tumor vascularity as markers for malignancy has
      been a subject of debate, with inconsistencies in specificity and sensitivity as
      well as in the diagnostic cut-off values. Part of the discrepancy might be
      explained by the limited number of vessels selected within the tumor for Doppler
      evaluation. A typical sample of three or four vessels may not be sufficiently
      large for correct representation of the vasculature of the tumor, which may
      contain many vessels. The existing conventional Doppler (color and spectral)
      techniques clearly have limitations. We present here a novel Doppler modality,
      namely two-dimensional spectral Doppler imaging (SDI), which allows the
      acquisition of many Doppler spectra within a few seconds. The operator selects a
      region of interest within a color Doppler image. The Doppler sequence is
      initiated and the entire selected region is automatically scanned for about 20 s
      until all spectral Doppler data have been acquired and processed. The system
      computer generates a color-coded map of the desired Doppler indices overlaid on
      the gray-scale image. The system also displays a cumulative histogram or a table
      of the requested Doppler index from all the sections in the tissue. The whole
      process is automatically performed by the system computer, without any need for
      operator intervention. The system provides the examiner with a 'fishing net' for
      Doppler indices, instead of the 'fishing hook' used in current techniques.

PMID- 9644777
TI  - Prenatal diagnosis of microcephaly assisted by vaginal sonography and power
      Doppler.
AB  - In two mid-trimester fetuses with microcephaly, transvaginal sonography revealed
      aberrant findings, including large subarachnoid spaces and a rudimentary shape of
      the lateral ventricles. In one of these fetuses, power Doppler ultrasound
      demonstrated a discrepancy in the size of the signals generated by the
      intracranial arteries branching from the internal carotids and those branching
      from the vertebral arteries, and this was interpreted as the consequence of a
      reduced blood supply to the undersized cerebral hemispheres. We suggest that
      evaluation of intracranial anatomy by transvaginal sonography and power Doppler
      examination of the cerebral vessels may be of value in the diagnosis of fetal
      microcephaly.

PMID- 9644778
TI  - Prenatal diagnosis of otocephaly using two-dimensional and three-dimensional
      ultrasonography.
AB  - We report a case of the prenatal diagnosis of a very rare anomaly, namely
      isolated otocephaly, using two-dimensional and three-dimensional ultrasound at 24
      weeks of gestation. Two-dimensional ultrasound revealed polyhydramnios, absence
      of a stomach shadow, hypotelorism and a proboscis-like mass. Three-dimensional
      ultrasound gave a precise demonstration of the striking craniofacial features of
      otocephaly including agnathia, synotia, microstomia and protuberance of the nose
      mouth fusion. The use of three-dimensional ultrasound provided a whole view of
      the very rare lethal malformation in utero and contributed significantly to
      prenatal diagnosis.

PMID- 9644779
TI  - Prenatal ultrasound diagnosis of massive subchorionic thrombohematoma.
AB  - Massive subchorionic thrombohematoma is a rare condition in which a large
      maternal blood clot separates the chorionic plate from the villous chorion. This
      condition is usually complicated by intrauterine growth restriction, and is often
      associated with fetal distress and perinatal death. We present a case in which
      the diagnosis of massive subchorionic thrombohematoma was made at 24 weeks'
      gestation. Doppler ultrasound helped to confirm the diagnosis and demonstrated
      severely abnormal umbilical blood flow. Two days after the diagnosis, fetal
      distress prompted emergency Cesarean delivery of a growth-restricted infant.

PMID- 9644780
TI  - Ultrasound diagnosis and follow-up of gestational trophoblastic disease.

PMID- 9644781
TI  - Endometrial pathology in hypertensive women.

PMID- 9644782
TI  - A critical review of penile revascularization procedures.

PMID- 9644783
TI  - Prognostic significance of p53 protein overexpression in transitional cell
      carcinoma of the renal pelvis and ureter.
AB  - Fifty-three patients with invasive transitional cell carcinoma of the renal
      pelvis and ureter were studied for p53 protein overexpression by
      immunohistochemistry. Overexpression of p53 protein was observed in 19 patients
      (35.8%). There was a significant correlation between overexpression of p53
      protein and histologic grade (p < 0.01). However, there was no correlation found
      between p53 immunoreactivity and pathologic stage. By univariate survival
      analysis, a significant difference in cumulative survival was observed between
      stage pT2 and stage pT3 or pT4 tumors (p < 0.05). The difference in survival
      between patients with p53-positive and negative tumors did not reach statistical
      significance (0.05 < p < 0.01). Multivariate analysis revealed that pathologic
      stage had an independent prognostic value (p < 0.05). The independent prognostic
      value of p53 protein overexpression did not quite reach statistical significance
      (p = 0.07). p53 protein nuclear overexpression appears to be a relatively weak
      prognostic indicator for patients with invasive transitional cell carcinoma of
      the renal pelvis and ureter.

PMID- 9644784
TI  - Cytokeratin 8/18 levels in patients with prostate cancer and benign prostatic
      hyperplasia.
AB  - OBJECTIVES: Recently, tissue polypeptide-specific antigen (TPS), a cytokeratin 18
      marker, was described to be discriminative between cancer of the prostate (CaP)
      and benign prostatic hyperplasia (BPH). Cyfra 8/18, a marker which recognizes
      both cytokeratin 8 and 18 fragments, is discussed to improve sensitivity and
      specificity of TPS. We investigated whether Cyfra 8/18 serum concentration
      discriminates between patients with clinically localized CaP and BPH. METHODS:
      Serum Cyfra 8/18 levels were determined in patients with untreated CaP before
      radical prostatectomy (pT1-3pNoMo; n = 11) and with histologically confirmed BPH
      (n = 22). Cyfra 8/18 concentration was correlated to the prostate-specific
      antigen (PSA) concentration. RESULTS: Median Cyfra 8/18 level was 0.64 ng/ml in
      CaP patients and 0.57 ng/ml in BPH patients. This difference is statistically not
      significant (p = 0.91). Furthermore, no correlation to PSA levels could be
      established (CaP: r = 0.036; BPH: r = 0.09). CONCLUSION: In contrast to a recent
      report we found the Cyfra 8/18 serum concentration to be a nondiscriminative
      parameter between CaP and BPH.

PMID- 9644785
TI  - Biphasic action of phenylephrine on the Ca(2+)-activated K+ channel of human
      prostatic smooth muscle cells.
AB  - The elevation of cytosolic Ca2+ ([Ca2+]i) is known to regulate smooth muscle
      contractility. A physiological concentration of phenylephrine induced the
      elevation in [Ca2+]i of human prostatic smooth muscle cells; however, contraction
      of prostatic tissues in vitro needs a higher concentration of phenylephrine than
      the physiological level. To investigate this discrepancy, we investigated the
      functional importance of the Ca(2+)-activated K+ channel (KCa channel) of human
      prostatic smooth muscle cells in phenylephrine-induced contraction. Using the
      patch-clamp technique, the KCa channel of human prostatic smooth muscle cells was
      activated by phenylephrine at a physiological concentration (10(-7)-10(-5) M) but
      was inhibited at a higher concentration (10(-4)-10(-3) M). Phenylephrine (10(-3)
      M) also inhibited the KCa channel which was activated by 10 microM A23187, a
      calcium ionophore. Similar inhibition was obtained with 1 microM phorbol 12
      myristate 13-acetate, an activator of protein kinase C (C-kinase). Both
      inhibitions were reversed by subsequent application of 1 nM staurosporine, a
      protein kinase inhibitor. These results suggested that C-kinase mediated the
      phenylephrine-induced inhibition of the KCa channel. In this study, a
      physiological concentration of phenylephrine induced activation of the KCa
      channel of human prostatic smooth muscle cells, which brought about membrane
      hyperpolarization and relaxation of human prostatic smooth muscle cells. The
      regulation of the KCa channel by phenylephrine may explain the need of a high
      concentration of phenylephrine for the contraction of prostatic tissue.

PMID- 9644786
TI  - Absorption of epirubicin instilled intravesically immediately after transurethral
      resection of superficial bladder cancer.
AB  - As postoperative adjuvant therapy for superficial bladder cancer, intravesical
      instillation therapy is commonly conducted. In this case, from the view point of
      prevention of intraoperative dissemination, commencement of instillation therapy
      at an early postoperative period is preferred. However, increased drug
      permeability is suspected because of damage to the bladder mucosa during
      operation. Therefore, this study was conducted to investigate the plasma level of
      epirubicin (EPI) instilled immediately after transurethral operation. EPI (20
      mg/40 ml or 50 mg/100 ml) was instilled immediately after a transurethral
      operation, and retained in the bladder for 1 h. Blood samples were obtained
      before instillation, as well as 30, 60, 120 and 240 min after instillation, and
      EPI levels were assayed. The mean EPI concentrations (ng/ml) among the 20-mg/40
      ml group (n = 5) were < 2.5 and < 2.0 at 30 and 60 min, respectively, after which
      they were undetectable. The 50-mg/100 ml group (n = 5) recorded 5.0, 4.4 and <
      3.0 after 30, 60 and 120 min, respectively, and after 240 min it was
      undetectable. Intravesical instillation of EPI immediately after a transurethral
      operation causes a small increase in the plasma level and it is thought to cause
      small systemic side effects.

PMID- 9644787
TI  - Renal needle biopsy along the retrograde puncture line of the renal calyx: a new
      promising technique.
AB  - The Biopty-gun is a useful tool in conducting percutaneous renal biopsies, but
      bleeding is still a significant complication. To reduce the rate of severe
      bleeding complications, we attempted a new method of renal needle biopsy using a
      retrograde access technique. Retrograde puncture of the renal calyx was performed
      using the Lawson nephrostomy kit. The 18-gauge needle of the Bioptygun was
      inserted along the puncture wire and fired. A 7-french pigtail catheter was
      retained in the renal pelvis for a few days following the procedure. This biopsy
      is a promising and safe technique.

PMID- 9644788
TI  - Operative course of transurethral resection of the prostate and progression of
      prostate cancer.
AB  - Surgery has the potential to disseminate cancer cells, and we therefore
      hypothesized that extensive transurethral resections of the prostate (TURP) would
      be followed by a worse prognosis than minor ones. For this purpose, the
      association between the extent of surgery, disease progression, and mortality was
      studied in 138 patients with prostatic cancer who had undergone TURP. The results
      show that a large bleed (> or = 275 ml) indicated a slightly increased relative
      risk of general progression of the cancer (relative risk (RR) = 1.9, 95%
      confidence interval (CI) = 0.9-4.1) and death (RR = 1.5, CI = 0.6-3.3). Other
      parameters of extensive surgery, such as the operating time and fluid absorption,
      were not associated with increased risk. Patients with a medical disease,
      however, such as hypertension and congestive heart failure, had a significantly
      higher relative risk of general progression (RR = 2.7, CI = 1.2-6.1) and death
      from prostatic cancer (RR = 4.6, CI = 2.0-10.7) in addition to an increased
      relative risk of death from other causes (RR = 3.7, CI = 1.3-10.5). We conclude
      that concurrent medical disease, but not an extensive TURP, worsened the
      prognosis of patients with prostatic cancer who underwent TURP.

PMID- 9644789
TI  - Primary erectile dysfunction in combination with congenital malformation of the
      cavernous bodies.
AB  - Primary erectile dysfunction in combination with congenital malformation of the
      cavernous bodies has only rarely been reported. We report on 2 young patients
      with different congenital malformations. To our knowledge this is the first time
      partial aplasia of the distal part of the cavernous bodies is described, whilst
      complete isolation of the cavernous bodies in combination with veno-occlusive
      dysfunction has yet been described in 3 cases. After complete examination,
      including penile angiography and cavernosometry, a surgical correction with a
      fully satisfying result was achieved in the patient with distal aplasia. In case
      of isolated cavernous bodies with severe veno-occlusive dysfunction, the
      implantation of a penile prosthesis remains the treatment of choice.

PMID- 9644790
TI  - Idiopathic partial thrombosis of the corpus cavernosum.
AB  - A case of spontaneous, partial, unilateral thrombosis of the corpus cavernosum is
      described. A 35-year-old white male presented with a painful mass in the perineum
      without priapism. Diagnostic evaluation with sonography and magnetic resonance
      imaging revealed a thrombosis in the left posterior corporal body. Treatment
      consisted of intravenous heparin followed by prophylactic acetylsalicylic acid.
      The thrombosis resolved spontaneously over several months without sequelae.
      Conservative management of this rare disease appears to be possible and safe.

PMID- 9644791
TI  - Erectile dysfunction due to single vessel failure: diagnosis and surgical
      treatment.
AB  - We report on the successful surgical treatment of venous single vessel disease in
      a patient presenting with erectile dysfunction. We stress the necessity of
      accurate diagnostic workup which enables the identification of rare cases that
      can be cured surgically.

PMID- 9644792
TI  - Isolated fibrinoid vasculitis in renal angiomyolipoma.
AB  - Renal angiomyolipoma is a tumor composed of a mixture of thick-walled blood
      vessels, smooth muscle, and mature adipose tissue. It may present as a single
      unilateral lesion or as a multifocal uni- or bilateral neoplasm. The histologic
      spectrum of angiomyolipoma is wide but as far as we know intratumoral fibrinoid
      vasculitis has not been described in the tumor. This is the first report of
      isolated intratumoral fibrinoid vasculitis observed in two nodules of a
      unilateral multifocal renal angiomyolipoma. The vasculitis arose in a
      hypertensive 62-year-old woman who presented with a history of dull right flank
      and low back pain of 3 months' duration. There were no signs of generalized
      disease. Immunophenotyping of the vascular cellular infiltrate disclosed abundant
      T lymphocytes, significant numbers of histiocytes, and absence of B lymphocytes.
      The diagnosis of isolated intratumoral arteritis depends on the exclusion of
      systemic disease. It is important to distinguish cases like this one to avoid
      misdiagnosis and to prevent unnecessary treatment.

PMID- 9644793
TI  - Pyelovenous fistula: an uncommon cause of 'essential haematuria'.
AB  - Haematuria from obscure lesions of the kidney sometimes pose both diagnostic and
      therapeutic challenge. Recently, we managed a patient in whom a confident
      diagnosis of pyelovenous fistula was made.

PMID- 9644794
TI  - Pelvic arteriovenous aneurysm caused by transurethral resection of the prostate:
      successful management by intra-arterial embolization.
AB  - We report a case of pelvic arteriovenous aneurysm caused by transurethral
      resection of the prostate. An abnormal vascular system was successfully managed
      by intra-arterial embolization using N-butyl cyanoacrylate in combination with
      platinum coil.

PMID- 9644795
TI  - A mullerian prostatic cyst protruding into the base of the urinary bladder.
AB  - The unique appearance of a midline prostatic cyst is reported. The cyst presented
      as a round-shaped filling defect at the base of the urinary bladder during an
      intravenous pyelography study. Transabdominal sonography showed the mass to be a
      midline prostatic cyst. The sonographic features of the mass and its location are
      the hallmark of a mullerian duct prostatic cyst. Midline prostatic cysts are
      discussed and the features differentiating mullerian duct cysts from utricle
      cysts are emphasized.

PMID- 9644796
TI  - Prostatic adenocarcinoma diagnosed by prostate-specific antigen analysis of
      pleural fluid.
AB  - Adenocarcinoma of the prostate may result in a malignant pleural effusion.
      However, most of these cases involve patients with either a known primary
      prostate cancer or radiographic evidence of pulmonary metastases. Occasionally,
      the initial diagnosis of prostate cancer is made because of prostate-specific
      antigen (PSA) staining cells in the pleural fluid. We report a case of
      adenocarcinoma of the prostate that was suspected only because of an elevated PSA
      in the pleural fluid in a patient who lacked malignant cytology, a history of
      prostate cancer, and radiographic evidence of pulmonary disease.

PMID- 9644797
TI  - Treatment of a recurrent bulbar urethral stricture after Urolume wallstent
      implantation with a second inner Urethrospiral-2 urethral stent.
AB  - Although the Urolume wallstent has been proven to be effective in the treatment
      of bulbar urethral strictures, in some instances obstruction may recur. We
      present a patient in whom recurrent stricture after wallstent implantation was
      managed by insertion of a second inner Porges Urethrospiral-2 stent inside the
      first one.

PMID- 9644798
TI  - Long-term outcome of a patient with intrascrotal extratesticular malignant
      schwannoma.
AB  - We have the opportunity to present a rare case of late local recurrence after
      treatment of intrascrotal extratesticular malignant schwannoma with
      rhabdomyoblastic features in an adult man. As our case is the first in the
      literature, we want to inform the reader about the long-term follow-up of our
      patient and suggest that these tumors may have a long survival and late
      recurrences may occur even after 5 years postoperatively.

PMID- 9644799
TI  - [The characteristics of the spatial organization of the human EEG in ketamine
      altered consciousness].
AB  - Spatial organization of human EEG was studied by means of topographic mapping
      methods with the multiparametric data estimations in the state altered by
      ketamine in terms of the concept of coherent structures of brain electrical
      activity. Two main features of the altered state of consciousness were reflected
      in the opposite shifts: an increase in the spatial synchronization in the left
      hemisphere (especially, in the posterior area) and its decrease in the left
      frontal and right temporal one. The obtained data are discussed from the
      viewpoint of dissociative effects of ketamine at the neurochemical and
      neurophysiological levels.

PMID- 9644801
TI  - [The human electroencephalogram during the mental recall of emotionally colored
      events].
AB  - The role of the left and right brain hemispheres in mental reproduction of
      emotional states by human subjects was analyzed using a new technique of EEG
      power spectral analysis in narrow frequency bands. At the maximal emotional
      tension joy was shown to be characterized by an increase in the alpha peak
      frequency. On the contrary, sorrow accompanied by a decrease in this value. We
      think that the left hemisphere (as well as the right one) participate in the
      development of emotional reactions.

PMID- 9644800
TI  - [The effect of a lesion of the subcortical conducting pathways on the electrical
      activity of the human cerebral cortex].
AB  - Simultaneous consideration of EEG, neurological, and imaging data obtained with
      sequelae of ischemic stroke during rehabilitation allowed us to verify the
      organic nature of some EEG phenomena. It was shown that stroke-induced impaired
      circulation in the area of the middle brain artery gave rise to deviant local
      cortical electrical activity (EA) in the form of polymorphic theta and delta
      waves or groups of theta waves. The character of such activity depended on the
      lesion size and extent of blood supply deficit in the damaged area. Decrease in
      the lesion size and restoration of blood supply during rehabilitation were
      accompanied by changes in the local deviant EA: the polymorphic slow-wave
      activity was replaced by single alpha and theta sharp waves. The restoration of
      motor functions was less successful in cases with the local deviant EA localized
      in the caudal part of the cortex.

PMID- 9644802
TI  - [The effect of vasopressin on hippocampal slices from trained rats].
AB  - Vasopressin effects were compared in hippocampal slices of control and
      conditioned rats. Continuous presentation both of paired and unpaired conditioned
      and unconditioned stimuli induced an increase in sensitivity of hippocampal
      neurons to vasopressin. This effect consisted in a complex biphasic reaction
      (excitatory-inhibitory modulation of population spike amplitude) to peptide
      application similar to the reaction of the control slices to the increased
      peptide concentration. The excitatory increased with the number of stimuli
      presentations and did not depend on the factor of learning. The inhibitory phase
      increased to a greater extent with the number of paired stimulations. It is
      suggested that the enhancement of depression by vasopressin in the trained
      animals in comparison with the active control most probably results from
      intracellular Ca2+ accumulation during conditioning.

PMID- 9644803
TI  - [The dependence of learning an active avoidance reaction on overcoming a problem
      solving situation in a shuttle box].
AB  - The two-way avoidance procedure dramatically differs from the one-way procedure
      in rate of learning. The present study was conducted to prove that retardation of
      the two-way avoidance acquisition resulted from development of the behavioral
      conflict tendency not to reenter the previous shock compartment. Cluster analysis
      of avoidance response indices divided rats into three distinctive classes. The
      occurrence of avoidance, escape, and freezing responses in the first session was
      analyzed in these three groups. Freezing during the shock action reflected the
      conflict tendency and showed a negative correlation with avoidance response
      indices. Only the rats which overcame the conflict and performed at least one
      avoidance reaction toward the end of the first session significantly improved
      their avoidance score in the following session. Discriminant analysis of indices
      of the three reaction types in the first session revealed sufficiency of these
      indices for prediction of the success in avoidance learning in subsequent
      sessions. Our results proved the hypothesis formulated previously that the
      conflict situation inherent to the two-way shuttle box procedure retarded the
      active avoidance acquisition. A number of trials have to be reserved in the first
      session for solving the conflict situation (direct effect on the rate of
      learning). The conflict intensity which directly effects the avoidance
      performance in the first session, presumably, influences learning in subsequent
      sessions (secondary effect on learning).

PMID- 9644804
TI  - [The study of individual differences as a method for dividing into stages the
      acquisition of a complex reflex].
AB  - Two-way active avoidance learning is a complex task characterized by a high level
      of interindividual variability. We have demonstrated in our previous paper that
      rats with different rate of learning vary in expression of freezing responses,
      which reflects a conflict tendency not to re-enter the previous chock compartment
      [4]. In the present work we analyzed as main indices the proportions of
      avoidance, rapid escape, and freezing responses and their distribution within a
      session. Sequences of occurrence of these three types of responses were examined
      in groups of rats with different success of avoidance learning. The obtained
      results confirmed a hypothesis that overcoming the conflict tendency was a
      separate stage of learning which preceded avoidance response appearance and
      subsequent stabilization. Only in rats which failed to learn and develop
      avoidance responses within the first session, freezing responses were observed in
      successive session being indicative of reappearance of the conflict tendency. The
      intensity of the conflict tendency did not depend on the type of the first
      response of an animal (fleeing or freezing) to an unexpected aversive stimulus.

PMID- 9644805
TI  - [The effect of serotonin antibodies on the behavior of C57Bl/6 mice in an open
      field and on the level of monoamines in the brain structures].
AB  - Mice of C57BL/6 strain were singly injected intraperitoneally with antibodies
      (AB) to serotonin (5-HT). The "open-field" testing in different periods after the
      AB injection revealed a depression of behavior within 1.5 h which changed for
      activation within 1 day and, again, depression within 5 days after the injection.
      The analysis of neurotransmitter content in the sensorimotor cortex and
      hypothalamus revealed increased levels of serotonin and, especially, dopamine in
      the cortex within 1 day. The cortex serotonin level within 5 days was also
      increased. The possible mechanisms are discussed of neurotropic action of AB to 5
      HT.

PMID- 9644806
TI  - [The effect of piracetam on the behavior of Nauphoeta cinerea cockroaches in an
      open field].
AB  - For 30 min the behaviour of 164 male cockroaches was studied in an "open field"
      analog. At the 31st min the electrical light was switched on and the examination
      was continued for 10 min. It was found out that the insects placed in the "open
      field" and subjected to a sudden illumination behaved in a similar way. After the
      initial freezing a sharp increase in the motor activity was observed with
      subsequent habituation. Per os administration of 200-400 mg/kg of piracetam (a
      solution of 5 mg of the drug and 500 mg of honey in 5 ml of water) did not change
      the freezing period but accelerated habituation and decreased the locomotion
      augmentation caused by the light. The obtained data suggest that piracetam
      improves memory and non-associative learning and exerts a stress-protective
      effect on cockroaches.

PMID- 9644807
TI  - [Posttetanic changes in the background gamma oscillations in interhemispheric
      interactions].
AB  - The influence of high-frequency microstimulation (HFMS) of one of the hemispheres
      on the parameters of spontaneous gamma-oscillations in the neural network
      containing callosal cells of the motor cortex of both hemispheres. There were
      three modes in the background oscillation periods distribution, which
      corresponded to the frequencies 40-60, 70-100, and 100-200 Hz. These oscillation
      frequencies were also revealed after the HFMS in neural interactions of the
      cells, which were active before the HFMS; the frequency 40-60 Hz, which dominated
      before the HFMS, became even more pronounced. The same three groups of
      oscillation frequencies were found in the activity of cells which became active
      after the HFMS. The expression of oscillations, the number of oscillatory
      interactions, as well as the number of neuronal pairs with additional
      synchronization decreased after the HFMS, which suggests a decrease in
      synchronization. Taking into account the results of simulation experiments that
      the frequency of gamma-oscillations is determined by the strength of inhibitory
      and excitatory input, we suggest that the long-term posttetanic modifications in
      the efficacy of synaptic inputs of the neurons of both hemispheres underlie the
      observed posttetanic changes.

PMID- 9644808
TI  - [The hypercolumns of the guinea pig visual cortex. The heterogeneity and
      multilevel topical organization of the projections].
AB  - Spatial distribution of neural responses to spots, slits, and bars in the guinea
      pig visual cortex reveals hypercolumns like those in the brain of higher mammals.
      The regular heterogeneities of topic projections within and between hypercolumns
      (reflected in a distribution of focal potentials in different cortical areas)
      suggest that the described columns are discrete cortical zones (or macromodules)
      about 0.6 mm in size. They consist of 7-10 on/off polar orientation micromodules
      about 0.2 mm in size. In turn, the latter also have the inner topical
      organization of their projections. Consequently, the described topical
      projections have a multilevel hierarchical organization of accordance with
      different complicity of neural structures. Taking into account the known polar
      structure of hypercolumns we think that it provides a possibility of comparison
      between the vectors of signals and polar structures. There are reasons to believe
      that this is a principle condition for signal recognition.

PMID- 9644809
TI  - [The initial level of motor activity determines the directivity of the motor
      effect of apomorphine].
AB  - In male mice of BALB/c and SHR strains with the highest base level of locomotion
      and rearings apomorphine (5 mg/kg) decreased these forms of motor activity while
      in C57BL/6 mice with the lowest base level of motor activity apomorphine
      increased it. In mice of C57BR and C3H/A strains with intermediate base level
      there was a tendency for an increase in activity. Extinction of exploratory motor
      activity in BALB/c as a result of four consecutive testings in the same
      experimental chamber with hourly intervals induced a decrease in activity of the
      animals by half. Being injected against this background the same dose of
      apomorphine (5 mg/kg) twice increased locomotion and rearings in these mice.

PMID- 9644810
TI  - [The striatum in the system of the central mechanisms of biorhythm control].
AB  - Striatum as a primary oscillatory brain structure participates in organization of
      the short-period pharmacogenous rhythms (amphetamine-induced stereotypy and
      haloperidol catalepsy) and time course of forced swimming. This form of activity
      can be controlled by the functional connections of the striatum with
      suprachiasmatic hypothalamic nuclei and pineal gland.

PMID- 9644811
TI  - [The properties of the benzodiazepine receptors of the rat cerebellum 6 months
      after korazol-induced kindling and recurrent seizures].
AB  - It was shown that the increased brain seizure readiness persisted within 6 months
      after termination of corazol kindling. Seizures of the same severity as during
      kindling (corazol injection in a dose of 20 mg/kg) were reproduced by corazol
      injection in a dose of 30 mg/kg. In contrast to the control rats, in this
      situation an autoenhancement of seizures was observed in the kindled animals.
      Acute corazol seizures induced a decrease in Bmax and Kd of 3H-diazepam binding
      with benzodiazepine receptors (BDR) in the cerebellum of the 10-months-old
      control rats white the young animals demonstrated only a decrease in Bmax of
      binding. In 6 months after kindling termination the BDR activity (Bmax) was
      reduced by one half. However, we think that the increase in Bmax is not
      responsible for persistence of the increased seizure readiness. It seems possible
      that down regulation of receptor activity develops independently of kindling but
      in response to long-lasting corazol application. Probably, Bmax spontaneously
      decreases after the termination of the long-term corazol application. The single
      dose of corazol (30 mg/kg) restores the changes in BDR density to the level when
      seizure readiness has been just fixed (6 months after kindling termination),
      independently of the primary receptor density.

PMID- 9644812
TI  - [The electrical activity of the brain structures in an experimental depressive
      syndrome induced by the systemic administration of 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine to rats].
AB  - In rats injected with neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP) the development of experimental depressive syndrome was accompanied by
      local epileptiform activity in the caudate-putamen complex and by reorganization
      of electrical processes in the brain. The spectral power density in the caudate
      putamen in the delta range was increased in the formative stage of depressive
      syndrome (day 3-4 from the beginning of MPTP administration) and in the stage of
      behaviour recovery (a week after the withdrawal) as compared to control rats. On
      the contrary, the spectral power in the alpha range was decreased at the peak of
      depression (day 11-12 from the beginning of neurotoxin administration) and a week
      after the withdrawal as compared to the initial value. In the formative stage of
      depressive syndrome the spectral power in the delta range was increased in
      hippocampus whereas in sensorimotor cortex it was decreased at the frequency 6 Hz
      compared to control. It is suggested that a new pathodynamical organization is
      formed in the CNS of animals in response to MPTP administration, which is thought
      to be a neuropathophysiological basis of depressive syndrome.

PMID- 9644813
TI  - [Brain monoamine oxidases in rats selected for their predisposition to pendular
      like movements of the head and shoulder girdle].
AB  - Brain MAO activity was studied in male rats from the strains bred from Wistar
      stock for predisposition to pendulum movements (PM+) and for the absence of such
      predisposition (PM-). By 16.00 o'clock, in PM+ rats MAO A activity significantly
      increased in the brain hemispheres and decreased in the brainstem. By this time,
      MAO B/MAO A ratio decreased in the hemispheres and increased in the brainstem.
      Emotional (immobilization) stress induced an increase in activity both of MAO A
      and MAO B in the brainstem of PM+ rats and increase only in MAO A activity in the
      hemispheres of PM- rats. Actinomycin D abolished the effect of stress on MAO A
      and MAO B in PM+ rats but increased MAO A activity in the hemispheres of PM-
      rats. Possible molecular modifications are discussed in regulation of MAO
      activity in PM+ rats.

PMID- 9644814
TI  - [The characteristics of the functional activity of the brain serotoninergic
      system in the manifestation of natural and pathological anxiety in mice: the
      effect of the genotype].
AB  - Anxiety was estimated in intact male mice of C57BL/6J (C57) and (CBA) and CBA/Lac
      (CBA) strains and in males of both strains after the repeated experience of
      social defeats (losers) in 10 daily aggressive confrontations. A plus-maze test
      for behavior in a novel situation and a partition test for communicative activity
      were applied. Tryptophan hydroxylase (TPH) activity, 5-hydroxytryptamine (5-HT)
      and 5-hydroxyindoleacetic acid (5-HIAA) levels were measured in the midbrain,
      hypothalamus, amygdala, hippocampus, and striatum in losers and controls (5 days
      of individual housing of intact animals). Intact C57 mice which demonstrated
      active avoidance in the maze had reduced TPH activity in the all studied brain
      regions compared to the intact CBA mice with passive behavior. The 5-HT
      catabolism in intact C57 was lower in the midbrain and hypothalamus and higher in
      amygdala, hippocampus, and striatum than in CBA mice. Chronic social stress led
      to expressed anxiety revealed by both tests in C57 losers in contrast to CBA
      ones. This anxiety was accompanied by an increase in 5-HIAA level and 5-HIAA/5-HT
      ratio in the midbrain as well as by an increase in 5-HT level and decrease in 5
      HIAA level and 5-HIAA/5-HT ratio in the hippocampus of C57 losers in comparison
      with the controls. Flesinoxan (0.5 mg/kg, i.p.), 5-HT1A receptor agonist, changed
      the communicative behavior of controls but was ineffective in losers. Thus, a
      decrease in sensitivity of 5-HT1A receptors was suggested in stress-induced
      anxiety of C57 losers. The less expressed anxiety in CBA losers was associated
      with less expressed changes in serotonergic metabolism. It is concluded that
      serotonergic mechanisms of pathological anxiety induced by the long-term social
      stress and those of natural anxiety in intact mice are different.

PMID- 9644815
TI  - [A quantitative morphological study of the effect of partial visual deprivation
      on the formation of 2 types of Wulst neurons in pied flycatcher nestlings].
AB  - Neurons of the Wulst area (analogous to mammalian visual cortex) were studied
      with the method of computerized morphometry (6 parameters) in frontal Golgi
      stained sections of pied flycatcher nestlings which were binocularly deprived
      since the age of 1-1.5 days post-hatching. The current study was focused on two
      types of neurons: spiny stellate and small spineless stellate-like cells. It was
      found that the visual deprivation not only slowed down the morphogenesis of these
      neurons but also caused the constructive changes--increase in the number of foci
      of maximal dendrite branching--in spiny stellate neurons which we had earlier
      defined as projective cells. Changes in small spineless stellate-like neurons
      (earlier defined as intercalate cells) were of, mostly, opposite direction. In
      the latter neurons we observed a reduction of the number of dendrites and
      dendrite branches. Opposite changes in different cell groups caused by the
      limitation of sensory input may, on the one hand, point to a difference in
      functional connections of ascending afferent fibers with different types of
      neurons, and, on the other hand, indicate a different degree of the influence of
      visual experience on the development of these neurons.

PMID- 9644816
TI  - [The place of the action of the serotoninergic system in the 2-stage process of
      the formation of latent inhibition in rats].
AB  - Activation of rat brain serotonergic system (injections of a selective serotonin
      reuptake blocker sertralin) at the stage of pre-exposition of the situation
      stimulus (placing into the illuminated compartment of the dark-light shuttle-box)
      intensified subsequent development of the latent inhibition at the stage of
      conditioning, which was measured by the latent period of transition to the dark
      compartment during the first testing after reinforcement of such transition with
      electrical shock.

PMID- 9644817
TI  - [The staining of the central neurons in the pteropod mollusk Clione limacina with
      fluorescein-labelled alpha-bungarotoxin].
AB  - FITC-labelled alpha-bungarotoxin (alpha BT[FITC]) was used to identify
      acetylcholine (ACh)-sensitive neurons in the central nervous system of pteropod
      mollusc Clione limacina. Two small symmetrical neurons were stained with alpha
      BT[FITC] on the dorsal surface of the cerebral ganglia. The staining was highly
      specific as it was completely blocked by preincubation in alpha-bungarotoxin
      [alpha BT] at very low concentration (10(-9) M). Nicotinic agonists and
      antagonists efficiently prevented alpha BT[FITC] staining while muscarinic
      agonists and antagonists had no effect. These findings confirm the suggestion
      that alpha BT[FITC] binds to nicotinic ACh receptors. The possible role is
      discussed of alpha BT[FITC]-stained cells in the complex of hunting behavior of
      Clione.

PMID- 9644818
TI  - [The problem of the origin of intellect and evolutionary biocybernetics].
AB  - The discussion proposed by L. M. Chailakhian in developed concerning the problem
      of the origin of the natural intelligence. It is stressed that studying the
      origin of logical thinking is very important. It is argued that the problem of
      the intelligence origin should be analyzed within the framework of general
      investigations of the evolution of biocybernetical system. This approach can
      constitute the powerful branch of science named evolutionary biocybernetics. The
      main lines of inquiry are characterized. The strategy is outlined of development
      of evolutionary biocybernetics: creation and development of basic mathematical
      models which characterize the key "intellectual inventions" of biological
      evolution. The examples are given of the models (the model of dominanta origin
      and the model of functional system in correspondence with P. K. Anokhin's ideas),
      which can be developed in the immediate future. The approaches are outlined to
      development of these models.

PMID- 9644819
TI  - [The orienting reaction and the conditioned reflex--a reaction to a predictable
      situation].

PMID- 9644820
TI  - [The functional asymmetry of the emotions].
AB  - A considerable body of neuropsychological and psychophysiological evidence
      suggests that the left hemisphere of the human brain is related to positive
      emotions, whereas the right hemisphere is related to negative emotions. R.
      Davidson and W. Heller (1993) suggested that it is determined by the ratio
      between the activities of the left and right regions of the frontal cortex.
      Comparison of these premises with those proposed by need-informational theory of
      emotions suggests that the right frontal cortex preferentially deals with
      pragmatic information (earlier experience stored in memory) required for
      satisfaction of the actual need, whereas the left frontal cortex processes most
      recent and currently available information. Unit activity of the prefrontal
      cortex was investigated in rats during stimulation of the emotionally positive
      (lateral hypothalamic area) and negative (dorsomedial tegmentum) structures. The
      asymmetry was revealed in neuronal responses: the prevalence of the left
      hemisphere during emotionally positive stimulation and of the right hemisphere
      during negative stimulation. Further research should provide more knowledge on
      the features of information processing by the left and right frontal cortical
      regions in humans and animals and elucidate the nature of interaction of these
      areas with need--and information-related cortico-limbic structures of the brain.

PMID- 9644821
TI  - Discrepantly poor verbal skills in poor readers: a failure of learning or
      ability?
AB  - Poor verbal skills in poor readers have long been reported in the literature.
      There have been many attempts to understand the interaction between poor verbal
      ability and poor verbal achievement. The methodological problems are
      considerable, including the measurement of verbal ability, which has been
      confounded by previous learning. A new reasoning test, the VESPAR, has been
      designed to measure novel problem solving and thus to be less reliant on acquired
      verbal skills. One hundred and seventy 14-year-olds completed the VESPAR, the
      Cognitive Abilities Test (CAT) and a single-word reading test. Overall, verbal
      scores were weaker than spatial scores. A subgroup of 38 pupils with particularly
      marked discrepancies between verbal and non-verbal CAT was identified. The
      especially discrepant pupils were matched with other non-discrepant pupils from
      the year group for either verbal or non-verbal CAT. The discrepant group's
      reading was at the same level as the matched verbal CAT group. However, the
      primary verbal ability of the discrepancy group, as measured on the VESPAR, was
      greater than the matched verbal CAT group. This raises the possibility that CAT-
      but not VESPAR-discrepant pupils may be at particular risk of under-achievement
      in the verbal domain.

PMID- 9644822
TI  - Derivation of a homesickness scale.
AB  - A 33-item measure of homesickness (the Homesickness Questionnaire, HQ) was
      derived from features of grief modified for the circumstance of separation from
      home. In three samples of year 1 students (N = 264) during their first year at
      university, total HQ scores were highly correlated with a single-item measure of
      homesickness used in previous studies, and 28 items showed significant
      differences between subgroups divided on the basis of the single-item scores.
      Previous findings that homesick students show more health and psychological
      symptoms, and cognitive failures, were supported by further comparisons between
      the two groups, and a meta-analysis of four studies. Factor analysis of the HQ
      indicated two factors, disliking the university, and attachment to the home,
      which are consistent with both the separation and strain models of homesickness.
      Correlations with other variables, and sex differences in the factor scores,
      further supported the distinction between these two aspects of homesickness.
      Women showed higher levels of intrusive thinking about the homesickness, but this
      was mediated by their higher scores on the attachment factor of the HQ. There was
      no sex difference in avoidant responses to homesickness.

PMID- 9644823
TI  - Differences between implicit and explicit acquisition of a complex motor skill
      under pressure: an examination of some evidence.
AB  - Masters (1992) argued that an implicitly acquired motor skill is less likely to
      fail under pressure than an explicitly acquired skill. He demonstrated this by
      showing that induced anxiety led to differences in the golf putting performance
      of groups who had acquired the skill implicitly and explicitly. We replicated
      Masters' basic findings but our results suggest that the difference in
      performance under pressure is more readily explained in terms of differences
      between the learning and testing conditions. Our results are consistent with an
      explicit learning account of the putting task and we found no support for the
      claim that implicit and explicit learning of motor skills are differentially
      affected by anxiety.

PMID- 9644824
TI  - Serial report and item recognition of novel visual patterns.
AB  - Previous studies of memory for novel visual patterns have reported how item
      recognition varies across serial positions, but have neglected serial order
      memory. In Expts 1 and 2 participants reported the order in which short series of
      novel patterns had been presented. The results showed markedly bowed serial
      position curves similar to those reported for sequences of verbal items or
      spatial locations. Concurrent articulation reduced performance in the serial
      report task relative to the memory task alone (Expt 2) or concurrent tapping
      (Expt 3) suggesting that a verbal component was involved. When two-alternative
      forced choice tests were used to test memory for the configuration of each
      pattern in the series, no primacy or recency was found (Expt 4). In Expt 5 the
      presentation of a series of five items was followed at random by either a serial
      report or the two-choice item recognition task. The serial position curves for
      the two tasks remained different, suggesting that encoding strategies were not
      responsible. The results show that bowed serial position curves are found when
      judgments of serial order are required, even when phonological coding is
      discouraged, whereas memory for item descriptions is independent of serial
      position. The implications for current conceptualizations of short-term memory
      are discussed.

PMID- 9644825
TI  - A species-specific satellite DNA from the entomopathogenic nematode
      Heterorhabditis indicus.
AB  - An AluI satellite DNA family has been cloned from the entomopathogenic nematode
      Heterorhabditis indicus. This repeated sequence appears to be an unusually
      abundant satellite DNA, since it constitutes about 45% of the H. indicus genome.
      The consensus sequence is 174 nucleotides long and has an A + T content of 56%,
      with the presence of direct and inverted repeat clusters. DNA sequence data
      reveal that monomers are quite homogeneous. Such homogeneity suggests that some
      mechanism is acting to maintain the homogeneity of this satellite DNA, despite
      its abundance, or that this repeated sequence could have appeared recently in the
      genome of H. indicus. Hybridization analysis of genomic DNAs from different
      Heterorhabditis species shows that this satellite DNA sequence is specific to the
      H. indicus genome. Considering the species specificity and the high copy number
      of this AluI satellite DNA sequence, it could provide a rapid and powerful tool
      for identifying H. indicus strains.

PMID- 9644826
TI  - Polymorphic microsatellites in Simulium damnosum s.l. and their use for
      differentiating two savannah populations: implications for epidemiological
      studies.
AB  - In West Africa, Onchocerca volvulus, the cause of human onchocerciasis, is
      transmitted by sibling species of the Simulium damnosum complex. Little is known
      about blackfly intraspecific variability and its consequences on vectorial
      capacity. This study reports the use of microsatellite markers for
      differentiating populations of S. damnosum s.l. Five microsatellite loci were
      characterized and used to analyze individuals from two savannah populations in
      Mali, 120 km apart. Four loci were highly polymorphic, having 8-12 alleles per
      locus and gene diversities ranging from 77.9 to 88.2%. A significant heterozygote
      deficiency was observed in the two populations. This may arise from inbreeding,
      population structure (the Walhund effect), or the presence of null alleles. To
      test this last hypothesis, new primers were designed for two loci and used to
      analyze homozygous individuals. After correcting for null alleles, heterozygote
      deficit persisted. Population subdivision in the two foci remains the most likely
      explanation. Our results indicate that microsatellite markers could differentiate
      fly populations, making them valuable tools for the study of population genetic
      structure.

PMID- 9644827
TI  - The nuclear ribosomal DNA intergenic spacers of wild and cultivated soybean have
      low variation and cryptic subrepeats.
AB  - The intergenic ribosomal DNA spacers (IGSs) from cultivated soybean (Glycine max)
      and wild soybean (Glycine soja) were sequenced and compared with six other
      legumes. These IGS sequences were 1821 bp in length in G. soja and G. max
      cultivars Arksoy, Ransom, and Tokyo, and 1823 bp long in the G. max cultivar
      Columbus. These represent the smallest published plant IGS sequences to data. Two
      clones from each of the above five cultivars were sequenced and only 22 sites
      (1.2%) were polymorphic, thereby supporting previous work that showed low genetic
      variation in cultivated soybean. The amount of variation observed between
      different clones derived from the same individual was equal to the amount seen
      between different cultivars. The soybean IGS sequence was aligned with six other
      published legume sequences and two homologous regions were identified. The first
      spans positions 706-1017 in the soybean IGS sequence and ends at a putative
      promoter site that appears conserved among all legumes. The second is located
      within the 5' external transcribed spacer, spans positions 1251-1823 in soybean,
      and includes sequences first identified as subrepeats IV-1 and IV-2 in Vicia
      angustifolia. Sequences homologous to these two subrepeats were identified among
      all legume species examined and are here designated "cryptic subrepeats" (CS-1,
      CS-2) given the range in similarity value (79-96% for CS-1 and 60-95% for CS-2).
      Comparisons of CS-1 and CS-2 sequences within individual species show that
      divergence (substitutional mutations, insertions, and deletions) is sufficiently
      high to obscure recognition of the repeat nature of these sequences by routine
      dot plot analytical methods. The lack of subrepeats in the 5' half of the soybean
      IGSs raises questions regarding the role they play in transcription termination
      or enhancement.

PMID- 9644832
TI  - The light gene of Drosophila melanogaster encodes a homologue of VPS41, a yeast
      gene involved in cellular-protein trafficking.
AB  - Mutations in a number of genes affect eye colour in Drosophila melanogaster; some
      of these "eye-colour" genes have been shown to be involved in various aspects of
      cellular transport processes. In addition, combinations of viable mutant alleles
      of some of these genes, such as carnation (car) combined with either light (lt)
      or deep-orange (dor) mutants, show lethal interactions. Recently, dor was shown
      to be homologous to the yeast gene PEP3 (VPS18), which is known to be involved in
      intracellular trafficking. We have undertaken to extend our earlier work on the
      lt gene, in order to examine in more detail its expression pattern and to
      characterize its gene product via sequencing of a cloned cDNA. The gene appears
      to be expressed at relatively high levels in all stages and tissues examined, and
      shows strong homology to VPS41, a gene involved in cellular-protein trafficking
      in yeast and higher eukaryotes. Further genetic experiments also point to a role
      for lt in transport processes: we describe lethal interactions between viable
      alleles of lt and dor, as well as phenotypic interactions (reductions in eye
      pigment) between allels of lt and another eye-colour gene, garnet (g), whose gene
      product has close homology to a subunit of the human adaptor complex, AP-3.

PMID- 9644833
TI  - Orthologous DNA sequence variation among 5S ribosomal RNA gene spacer sequences
      on homoeologous chromosomes 1B, 1D, and 1R of wheat and rye.
AB  - 5S ribosomal gene spacer sequences from the short-spacer arrays of wheat and rye
      were isolated by PCR. The 29 new DNA sequences displayed noticeable heterogeneity
      at scattered positions. Nevertheless, based on shared DNA sequence polymorphisms,
      sequence alignment clearly classified the sequences into three groups. Group
      specific primer sets were designed to allow chromosomal assignment by PCR on
      nullitetrasomic wheat stocks, as well as on wheat-rye translocation and addition
      lines. The three groups were assigned to orthologous loci 5S-Rrna-B1, 5S-Rrna-D1,
      and 5S-Rrna-R1 on homoeologous chromosomes 1B, 1D, and 1R, respectively. Hence,
      group-specific DNA sequence variation could be related to fixed orthologous DNA
      sequence variation between 5S rRNA multigene families on the homoeologous group 1
      chromosomes. In addition, members of the three groups showed fixed orthologous
      length polymorphism. Four sequenced 5S-Rrna-B1 units, however, had a duplication
      in the gene encoding region and are probably representatives of a nontranscribed
      subfamily of 5S rDNA repeating units. The observed chromosome-specific
      polymorphisms among sequences belonging to a multigene family with thousands of
      copies suggests that this type of polymorphism may exist in many genes and gene
      families in polyploid wheats. The implication of this finding in relation to the
      construction of molecular tools for wheat-genome analysis and manipulation is
      discussed.

PMID- 9644834
TI  - Recovery of a marked translocation strain that will facilitate the isolation of
      balancer chromosomes in the Mediterranean fruit fly, Ceratitis capitata.
AB  - The results of two screens for mutations and chromosomal aberrations in Ceratitis
      capitata are presented. Three dominant mutations were recovered, including Sb,
      which is associated with a homozygous lethal translocation between the third and
      fifth chromosomes, T(3;5)Sb, with the fifth chromosome breakpoint adjacent to y.
      The T(3;5)Sb chromosome is maintained by selecting for Sb in a T(3;5)Sb, w2 Sb y2
      wp/w2 y2 wp stock and can be used to distinguish between other chromosomes
      carrying differential combinations of the recessive markers w2 y2 wp. The ability
      to isolate particular marked chromosomes is essential in order to recover an
      inversion-based balancer chromosome. In addition to the recovery of dominant
      mutations, gamma-ray induced somatic mosaics of w2 and y2 and zygotic w mosaics
      were found. The generation of zygotic mosaics following mutagenesis can give
      mutants with a mosaic germ line that fail to breed true in the first generation.
      A screen of 22,830 irradiated chromosomes failed to recover variegating alleles
      of w, although such alleles might be recovered in a larger screen. The high
      frequency of dominant mutations and the instability at the w locus in our stocks
      implies a background level of dysgenic activity. These results have implications
      for the construction and long-term maintenance of genetically modified strains.

PMID- 9644837
TI  - An X/Y DNA segment from an early stage of sex chromosome differentiation in the
      fly Megaselia scalaris.
AB  - The sex chromosomes of the Megaselia scalaris wild-type strain Wien are
      homomorphic. We studied a roughly 1.8 kb X/Y DNA segment of this strain. It
      includes, at one end, the first part of a coding sequence for a protein of the
      vespid antigen 5 family. Molecular differentiation between the X and Y
      chromosomes has commenced, but homology, even of short DNA stretches, is still
      assessable beyond doubt. The most conspicuous differences between the X and the
      homologous Y segment were insertions/deletions in the noncoding region: among
      them, deletions, a duplication, and an insertion of a mobile element. These
      structural changes grossly disrupted homology. In comparison, base substitutions,
      though more numerous, contributed little to the differentiation of the X/Y DNA
      segment.

PMID- 9644838
TI  - The Drosophila gene asteroid encodes a novel protein and displays dosage
      sensitive interactions with Star and Egfr.
AB  - The asteroid gene of Drosophila was found to lie within 189 bp of Star. Asteroid
      cDNA clones were isolated and sequenced and a single putative open reading frame
      was identified that encodes a novel protein of 815 amino acids with a calculated
      molecular mass of 93 kilodaltons. Using cDNA probes, asteroid transcripts were
      localized to the proliferative tissues of embryos and to the mitotically active
      tissue anterior to the morphogenetic furrow in eye imaginal discs. Ribonuclease
      protection assays identified a mutation of asteroid that acts as a dominant
      enhancer of Star mutations and also enhances the Ellipse mutation, EgfrE1. Based
      on these data, a model for asteroid gene function in EGF receptor signaling is
      presented.

PMID- 9644840
TI  - [Prevalence of respiratory diseases in the textile industry. Relation with dust
      levels].
AB  - Many workers in the textile industry have respiratory symptoms that are related
      to their work environment. In this study we observed the dust level conditions of
      eleven textile industries of the North of Portugal. The dust levels determined
      were between 0.1 mg/m3 and 1.25 mg/m3, in many cases above the Portuguese
      standard levels of exposure (VLE). For these dust levels we found a prevalence of
      23% of workers with respiratory symptoms with occupational characteristics in
      10.8%, and 5.7% presenting byssinosis. Workers exposed to cotton fibres in
      spinning areas have the highest prevalence of symptoms, and reduction of the
      FEV1. These characteristics were related to dust levels and were higher in the
      initial phases of the spinning processes. We found no cases of byssinosis in
      workers exposed to synthetic fibres, or in workers from weaving areas. Smoking
      habits were related to the reduction of the FEV1, and severity of respiratory
      illness but not to the presence of byssinosis.

PMID- 9644841
TI  - [Diet and risk of myocardial infarction. A case-control community-based study].
AB  - OBJECTIVE: To evaluate diet as a risk factor for myocardial infarction. DESIGN:
      Community based case-control study. SETTING: University Hospital, Oporto.
      PARTICIPANTS: First time consecutive cases of acute myocardial infarction (n =
      100) and 198 community controls, older than 39 years and living in Oporto, were
      compared. METHODS: Data were collected by trained interviewers using a structured
      questionnaire designed to obtain information on socio-demographic, medical and
      behavioural aspects, emphasising the description of diet and food habits (using a
      semi-quantitative food frequency questionnaire). Controls were selected by random
      digit dialing with a participation rate of 70%. Odds ratios and 95% confidence
      intervals (CI) according to quartiles of nutrient ingestion were calculated using
      unconditional logistic regression. RESULTS: Female controls presented
      significantly higher mean intakes of protein, omega-3 fatty acids, fiber,
      cholesterol and vitamin C. Male controls had a significantly higher mean daily
      intake of fiber, vitamin C, vitamin E, and carotenes. After adjusting for age,
      sex, education, body mass index, ethanol, smoking and total energy intake, there
      was a protective effect of vitamin C (OR = 0.2, 95% CI: 0.1-0.6, for the 4th
      quartile), vitamin E (OR = 0.3, 95% CI: 0.1-0.9 for the 4th quartile) and total
      fiber (OR = 0.3, 95% CI: 0.1-0.9) for the 4th quartile). No significant effect
      was found for trans-fatty acids, but there was a higher risk with increased
      energy intake. CONCLUSIONS: This study showed that diet has an important
      independent effect on myocardial infarction, a protective independent role for
      anti-oxidant vitamin C and E was verified.

PMID- 9644842
TI  - [Acute complications of diabetes mellitus].
AB  - A retrospective study was made of 83 diabetic patients admitted to the Department
      of Internal Medicine between January 1986 and December 1993, with acute
      intercurrence of the disease. The authors considered some clinical features (age,
      type and frequency of complication, form of presentation, causal aetiology,
      laboratory findings and therapeutic options). Statistical relationships between
      different populations were made using the unpaired Student's T. method. Results
      were compared with those in the literature, leading to some significant
      conclusions.

PMID- 9644843
TI  - [Economic impact of a health care program on antibiotics].
AB  - The increased use of more expensive broad-spectrum antibiotics has had an impact
      on health care costs and the potential emergence of antimicrobial resistance.
      Antimicrobial drug prescription programs resulted in a significant reduction in
      the inappropriate use of certain antibiotics and in the pharmacy budget. The
      authors present the economic impact of an antimicrobial drug prescription program
      in a small community hospital.

PMID- 9644844
TI  - [The use of endoprosthesis in superior vena cava syndrome caused by lung
      neoplasms].
AB  - We present six cases of superior vena cava syndrome caused by a malignant tumor
      that were treated by percutaneous endoprostheses. The technique is described and
      the results evaluated. In one case there was acute thrombosis of the
      endoprosthesis that was treated by urokinase. No other complications were
      observed. A patient died one month later due to progression of the tumor. The
      remaining cases were asymptomatic for longer than 6 months. It was concluded that
      endoprostheses for superior vena cava syndrome are efficient, with quick
      improvement of the symptomatology.

PMID- 9644845
TI  - [Monoclonal antibodies. General approach and radioimmunotherapy].
AB  - Two major obstacles to systemic cancer therapy are the lack of specificity of
      therapeutic modalities and the intrapatient and interpatient heterogeneity of
      cancer cells. Because of their natural specificity, antibodies directed against
      tumor specific or tumor associated antigens have been raising interest in
      oncology. This article makes an overview of the basic principles of monoclonal
      antibodies, their limitations and perspectives, with particular attention to
      Immunoradioconjugates. The most important Immunoradiotherapy clinical studies are
      also reviewed.

PMID- 9644846
TI  - [Lupus anticoagulants versus antiphospholipid antibodies].
AB  - The antiphospholipid antibodies (aPL) present in "antiphospholipid-protein
      syndrome and autoimmune disorders" are associated with thromboembolic episodes,
      such as venous and/or arterial thrombosis and fetal loss. Patients with
      antiphospholipid antibodies have, by definition, laboratory abnormalities in
      either coagulation assays or various solid phase immunoassays ELISA or
      radioimmunoassays (RIA). These assay systems were initially thought to detect
      antibodies against phospholipids. The problem was complicated when it was
      reported that phospholipid is not the sole antigen but only a part of it, the
      other contribution being due to b2-glycoprotein I (b2-GP I). More findings,
      demonstrate that the aPL are in fact anti-b2-GP I antibodies directed against a
      epitope which is expressed when b2-GP I is bound to anionic phospholipid or
      another suitable surface. Recent studies have demonstrated that antibodies
      related to lupus anticoagulant (LA) induce an anticoagulant activity in b2-GP I.
      Some of these LA require binding to phospholipid. However, not all LA require b2
      GP I as a cofactor. Human prothrombin is an antigen for some LA IgG's. Finally, a
      subclassification of phospholipid-dependent coagulation test anticoagulants is
      described, there appear to be several subclasses of LA, and the clinical and
      laboratory criteria required to establish the diagnosis of antiphospholipid
      protein syndrome is emphasised.

PMID- 9644847
TI  - [Bioartificial liver].
AB  - Fulminant hepatic failure remains without satisfactory medical treatment and with
      a mortality rate of nearly 90%. Liver transplantation is the only chance to save
      these patients. However, there is a shortage of donors and many patients die
      before transplantation. It is thus necessary to develop a liver support system to
      help maintain patients alive, neurologically intact until an organ becomes
      available for transplantation, or ideally until hepatic regeneration. Early
      systems had only a depuration function, but now these systems include hepatocytes
      to replace most hepatic functions.

PMID- 9644848
TI  - [Y chromosome and male infertility].
AB  - Spermatogenesis is a complex physiological process characterized by an orderly
      proliferation and differentiation of germ cell types, from diploid spermatogonial
      stem cells to haploid spermatids, and after spermiogenesis to spermatozoa. It is
      known that male reproductive capacity is deficient in about one half of infertile
      couples. Effective treatment is available only for a small fraction of these
      infertile men. In most cases, the cause of male infertility is unknown.
      Aetiologically, male infertility may result from genetic and non-genetic causes.
      Among the genetic factors known to disturb spermatogenesis, chromosomal
      aberrations, involving autosomes and/or sex chromosomes, are well known. However,
      molecular genetic causes of idiopathic male infertility have been accumulating in
      the last years, predominantly for the Y chromosome. Localization of genes that
      control spermatogenesis on Yq11 was first proposed, on cytogenetic evidence, by
      Tiepolo and Zuffardi in 1976. Since then, many subsequent reports using molecular
      genetics methods have supported the initial proposal by detecting submicroscopic
      interstitial deletions on Yq11, present in patients with idiophatic azoospermia
      and a cytogenetically normal Y chromosome. Recently, four spermatogenesis
      candidate Y-linked genes (or gene families), RBM, DAZ, SPGY and TSPY have been
      cloned and characterized. In the euchromatic Y chromosome long arm three
      intervals--AZFa, AZFb and AZFc--were also defined. All of them may contain genes
      necessary for normal spermatogenesis. All the four genes have a testis-specific
      expression and three of them (RBM, DAZ and SPGY) code for ribonucleoproteins with
      a single RNA recognition motif. Candidate genes with in AZFb are some members of
      the RBM gene family and within AZFc are the DAZ and SPGY gene family. While AZFc
      deletions are associated with azoospermia or with severe
      oligoteratoasthenozoospermia, microdeletions involving AZFa or AZFb cause
      azoospermia only.

PMID- 9644849
TI  - [Modern ethics. Various considerations, particularly based on hospital
      experience].
AB  - The four basic principles of modern medical ethics are presented and discussed.
      The historic evolution of the hospital is analysed concerning the organisation
      and the social function of the hospital. The author presents some considerations
      about the relation between the patient and the hospital, clinical investigation
      and informed consent, confidentiality and technological progress. The problems of
      the end-of-life of the hospitalised patient is discussed, with an overview of the
      do-not-resuscitate orders.

PMID- 9644850
TI  - [Aneurysms of the interatrial septum].
AB  - Atrial septum aneurysms are an uncommon condition, underestimated before the
      routine use of echocardiography. Their clinical importance has increased after
      being associated with thromboembolic events. The authors made a review of
      clinical, diagnostic and therapeutic features of this entity after reporting six
      clinical cases.

PMID- 9644851
TI  - [Refractory severe ulcerative colitis. Experience with cyclosporine].
AB  - A case of severe ulcerative colitis refractory to steroid therapy is reported.
      The authors look at cyclosporine use in this clinical setting and make a short
      review of cyclosporine usefulness and major side effects.

PMID- 9644853
TI  - [Therapeutic recommendations].

PMID- 9644852
TI  - [Atypical radiologic features of pulmonary tuberculosis. Nodular images in
      strings of balloons].
AB  - Chest radiographs are an important tool for the diagnosis and follow-up. Yet the
      radiographic findings can vary significantly, ranging from the so-called usual to
      unusual patterns. In this paper the authors report three cases of pulmonary
      tuberculosis in which the chest radiographs showed a nodular, pseudo-tumoral
      pattern. Based on literature and on their own experience, the authors discuss the
      frequency of this radiologic presentation in this setting and its correlation
      with the immunological status of the patient, the pathogenicity of Mycobacterium
      tuberculosis and the clinical presentation of the disease.

PMID- 9644854
TI  - [Paragangliomas of the head and neck. Our experience].
AB  - Paragangliomas of the head and neck are rare tumors of neuroectodermal origin.
      However, jugulotympanic paragangliomas are the second most common tumor of the
      temporal bone. Paragangliomas are recognized as benign tumors, but some show a
      biological behavior similar to that of malignant lesions, such as the development
      of recurrence or invasive growth patterns. We report 31 patients with a total of
      35 paragangliomas who were seen in our department. Multiple paragangliomas were
      found in 2 patients. Twenty-two patients had jugulotympanic paragangliomas, 11
      carotid and 2 vagal paragangliomas. None of the patients had prior treatment and
      the minimum follow-up was 1 year. Surgery was performed in 28 (90%), primary
      irradiation in 1 (3%), and 2 (7%) refused treatment. We describe our results, the
      clinical course, diagnostic methods and treatment options.

PMID- 9644855
TI  - [The sensorineural component of hearing loss associated with cholesteatoma].
AB  - Patients with cholesteatoma often suffer neurosensorial hearing loss with
      variable bone conduction thresholds. Its origin is debated and has been
      attributed to the ototoxicity of topical drugs, immune reactions, effects of
      ototoxic antibiotics applied to the ear, etc. A selected series of 50 patients
      who underwent surgery for chronic ear disease due to cholesteatoma in our ENT
      department were studied to evaluate the possible origin of the bone conduction
      component of hearing loss. Different clinical, audiological, and surgical aspects
      were analyzed, including cholesteatoma site and extension, age, sex, evolution of
      the symptoms, pure tone audiometry data, middle ear involvement, the operation
      performed, and the occurrence of complications. Bone conduction thresholds were
      reported as pure tone differential thresholds (affected vs non-affected ear). A
      specific cholesteatoma-related neurosensorial hearing loss was observed that
      might lead to irreversible hearing loss. Neurosensorial involvement seems to be
      related mainly to the duration of symptoms, type of surgery, certain specific
      clinical aspects, and complications.

PMID- 9644856
TI  - [Sudden deafness. Experience at our hospital].
AB  - A retrospective study was made of 60 patients (61 ears) who were hospitalized for
      the study and treatment of sudden hearing loss. Data were compiled on the hearing
      loss and hearing gain after treatment. Hearing loss was unrelated with age or the
      appearance of vestibular symptoms. After hemodilution, steroid, and vasodilator
      treatment, 47.6% showed a hearing gain of up to 20 dB. The gain was significantly
      less (p < 0.05) in patients suffering vertigo. It also was less in patients who
      delayed treatment and in those with severe hearing loss in the high-tone
      frequencies, but these differences did not reach significance. The recovery
      period ranged from 2 days to 2 months, with 48% showing improvement in the first
      week.

PMID- 9644857
TI  - [Epidermoid carcinoma of the nasal septum].
AB  - Squamous-cell carcinoma of the nasal septum occurs infrequently and only a few
      cases have been reported. Because of the small number of cases, comparisons
      between treatment groups have been inadequate. Five patients with this type of
      tumor are presented. All of them underwent surgery (4 as primary treatment and 1
      for recurrence after radiation therapy). One patient had a local recurrence, 2
      had cervical metastases, and 2 (40%) died as a consequence of the tumor. In the
      squamous cell carcinoma of the nasal septum our study supports surgical resection
      with wide margins combined with postoperative irradiation as the preferred
      treatment with prophylactic neck dissection for tumors over 2 cm or extended to
      adjacent areas.

PMID- 9644858
TI  - [Laryngo-tracheoplasty in the management of infantile laryngeal stenosis].
AB  - We present the results obtained in our center with laryngo-tracheoplasty for the
      management of laryngeal stenosis in infants and children. Nineteen patients were
      treated between 1989 and 1995. Their weights ranged from 1,200 g to 36 kg. Twenty
      five operations were performed, not including endoscopic maneuvers. Fifteen
      patients have been decannulated (79%). Complications were infrequent and resolved
      satisfactorily. We consider that these surgical procedures should occupy a
      prominent place in the management of pediatric patients with laryngeal stenosis.

PMID- 9644859
TI  - [Mortality in laryngeal cancer surgery].
AB  - The causes of death were studied in a series of 171 patients who died in a 5-year
      follow-up period, out of a total of 631 patients who underwent different surgical
      techniques for cancer of the larynx. MATERIAL AND METHODS: The case histories of
      631 patients who had undergone surgery between 1974 and 1990 were reviewed; 83
      did not have a 5-year follow-up and were excluded from the study. A descriptive
      and inferential statistical study was made of the remaining cases to determine
      the relation between cause of death and tumoral extension, primary location,
      degree of tumoral differentiation, surgical technique and other data. RESULTS:
      Ninety-one patients died from local or regional recurrence, 50 from distant
      metastases, 20 from diseases other than the tumor, and 10 from postoperative
      complications. These findings were studied with regard to factors such as tumor
      extension, location, surgical technique, etc. CONCLUSIONS: The main cause of
      death in surgery for cancer of the larynx was recurrence, either local, on the
      tumor bed (62 patients) or regional (29 patients). The mortality rate was higher
      in older patients, patients with lymph-node involvement in the postoperative
      histological study, and patients with less differentiated histological forms.

PMID- 9644860
TI  - [The study of postoperative infection in patients after laryngeal cancer
      surgery].
AB  - We evaluated wound infections in major oncological surgery for laryngeal neoplasm
      and functional neck dissection. Our objective was to determine the incidence and
      prevalence of infection in a group of laryngectomized patients; we evaluated the
      temperature, duration of fever, and analytical findings in the postoperative
      period, antibiotic prophylaxis, and the treatment of infectious complications. A
      retrospective study was designed to examine the infectious complications that
      appeared in 97 patients who underwent laryngectomy and neck dissection for
      laryngeal carcinoma from 1994 to 1996 in an ENT department. Factors that
      influence wound infection were examined: fever, granulocytopenia, preoperative
      assessment, bacteriological culture, therapy and prophylaxis, and treatment. The
      data were analyzed statistically and compared with findings by other authors.

PMID- 9644861
TI  - [Head and neck symptoms of gastroesophageal reflux].
AB  - In otorhinolaryngology, the relationship between gastroesophageal reflux (GER)
      and pharyngolaryngeal disorders is well-known. In fact, many patients with GER
      debut with head and neck symptoms or are first seen by an otolaryngologist. We
      proposed to identify the ENT symptoms most frequently associated with GER, to
      differentiate between physiological and pathological GER, and to confirm the
      effectiveness of antacid treatment. Our study included 20 ambulatory patients who
      presented pharygolaryngeal symptoms and clinical manifestations of GER (heartburn
      and regurgitation). The patients underwent a complete ENT examination and were
      referred to a gastroenterologist for esophagoscopy, manometry, and 24-hour pH
      monitoring. All patients received antireflux therapy for one month (ranitidine
      150 mg given twice daily). We conclude that GER produces a variety of
      manifestations, but the most frequent pharyngolaryngeal symptoms and physical
      findings were globus pharyngeus and erythema of the arytenoids, respectively.
      Pathological GER was found in only one third of our patients and 90% responded
      well to treatment.

PMID- 9644862
TI  - [Risk factors in surgical wound infection in oncological surgery of the head and
      neck].
AB  - Although the use of antibiotic prophylaxis has significantly reduced the
      frequency of postoperative wound infections, they continue to be a critical issue
      in head and neck cancer surgery. A study was made of possible risk factors for
      the development of these infections. A prospective study was made of 159 patients
      with pharyngo-laryngeal squamous-cell carcinoma who underwent open-pharynx
      surgery in order to analyze the factors associated with wound infections.
      Postoperative wound infection was defined as purulent drainage or mucocutaneous
      fistula formation, or both, in the first 10 days after surgery. Potential risk
      factors examined were age, medical illnesses, prior surgery and radiotherapy, TNM
      stage, type of operative procedure, method of reconstruction, and operative time.
      The overall wound infection rate was 23%. Although the incidence of wound
      infection was higher in patients who received preoperative radiotherapy, in
      patients with advanced stage disease, and in those who required flap
      reconstruction, the only preoperative factor that significantly increased the
      rate of wound infection was the concurrence of medical illnesses (chronic
      obstructive pulmonary disease and diabetes mellitus; p = 0.018). In conclusion,
      the presence of prior medical diseases was the main risk factor in the
      development of postoperative wound infections.

PMID- 9644863
TI  - [Specialized care in pediatric otorhinolaryngological emergencies].
AB  - Emergency care for pediatric patients represents a large proportion of total ENT
      emergencies so we thought that it might be interesting to know the statistical
      data from a tertiary hospital. These findings are the basis for planning work and
      training for future specialists in different fields.

PMID- 9644864
TI  - [Primary health care in otorhinolaryngology. Descriptive study].
AB  - We present a one-year study describing the ENT pathology seen in a rural ENT
      clinic. The study included 1,516 patients whose characteristics are described
      (age, sex, diagnosis, and others).

PMID- 9644865
TI  - [Middle ear carcinoma].
AB  - Middle-ear cancer represents 5 to 10% of all ear neoplasms. Risk factors include
      chronic suppurative pathology of the middle ear and prior irradiation. Most
      malignant tumors are squamous-cell carcinomas. We report the case of a 51-year
      old woman with this process. The ideal treatment is mastoidectomy or pterosectomy
      followed by radiotherapy. We made a bibliographic review of the clinical
      manifestations, diagnosis, treatment, and prognosis of middle-ear cancer. Five
      year survival rates range from 25 to 50% in patients who undergo surgery and
      radiotherapy.

PMID- 9644866
TI  - [Langerhans cell histiocytosis. Report of four cases].
AB  - Langerhans cell histiocytosis implies the proliferation and accumulation of
      anomalous, cytologically benign tissue macrophages in a given site. In the
      Hospital General y Universitario of Alicante, Spain, from 1975 to 1996 four
      patients presented with granulomatosis and otorhinolaryngological signs and
      symptoms: a 7-year-old girl with a right mastoid eosinophil granuloma, a 2-month
      old boy with Letterer-Siwe syndrome whose illness started as acute mastoiditis, a
      23-month-old boy who developed eosinophil granulomas of both mastoids and one
      ischium, and an 8-month-old girl with a right zygomatico-temporal eosinophil
      granuloma. The treatment and clinical course of each case is described and
      compared with the results of other authors.

PMID- 9644867
TI  - [Fungal sinusitis. Report of four cases].
AB  - Fungal sinusitis has a nonspecific clinical presentation, is refractory to
      standard medical treatment and may produce expansion and erosion of the sinus
      wall. Various factors have been implicated in the development of fungal
      sinusitis: anatomical factors in the osteomeatal complex, tissular hypoxia,
      traumatic factors, massive exposure to fungal spores, allergy and
      immunosuppression. Our study of four cases diagnosed in the department included
      the clinical, pathological, and radiological features of fungal sinusitis. Five
      forms are described. Bacterial infection often occurs. The diagnosis of fungal
      sinusitis requires a high level of clinical and pathological suspicion. Before
      surgery, fungal sinusitis is suggested by the clinical and radiological features,
      and is confirmed by histological study. Culture of the tissue sometimes leads to
      identification of the fungus. Surgical removal of the infection is the main
      treatment for every form of fungal sinusitis.

PMID- 9644868
TI  - [Paranasal sinus chondrosarcoma. A case report].
AB  - We report a case of chondrosarcoma of the nasal cavity and paranasal sinuses.
      These cartilaginous tumors are rare in the head and neck. The treatment of choice
      is surgery.

PMID- 9644869
TI  - [Electromyographic study of pharyngeal soft palate paralysis or Vernet syndrome].

PMID- 9644870
TI  - [Cervical cutaneous leishmaniasis].
AB  - A case of cutaneous leishmaniasis that presented as a large cervical ulceration
      is reported. The etiopathogenesis, clinical manifestations, diagnosis, and
      treatment are reviewed. The visceral and mucocutaneous forms of the disease were
      excluded from this study.

PMID- 9644871
TI  - [Simplified videonystagmoscopy].
AB  - Videonystagmoscopy visualizes nystagmus on a television monitor and records it on
      video tape for later study, records, and reproduction. Early attempts date from
      long ago, but the technique only recently has spread, since the development of
      complex computerized equipment which, however, confines it to certain vestibular
      exploration laboratories. In order for this technique to become more widely used,
      simple equipment is needed, such as that described in this article. Our system
      consists of a single infrared light minivideo camera that is attached to the left
      eye using an eyeglass-mounting system that also occludes the right eye. The
      examination method is routine. Our results show the following advantages over
      electronystagmography: visualization of the rotary component, non-interference of
      visual stimuli, mechanical and electronic stability, speed, and low cost. If
      necessary, it can be complemented by electronystagmography and computer analysis.

PMID- 9644872
TI  - [Chronic elevation of enzymes of pancreatic origin in asymptomatic patients].
AB  - Chronic asymptomatic elevation of pancreatic enzymes is a well known entity
      although little has been reported. In most cases chronic asymptomatic elevation
      of amylase is due to a salival isoamylase increase or macroamylasemia. However,
      we have studied 10 cases with an increase in amylases due to pancreatic
      isoamylase and an increase in the remaining pancreatic enzymes which remained
      elevated during the follow up period ranging from 2 to 60 months. The amylase
      values ranged from 186 to 1,600; the lipase from 176 to 3,989, trypsin from 476
      to 2,430 and pancreatic isoamylase from 122 to 1,263. In all patients CT and
      echography were carried out, which discarded structural damage. Nonetheless, an
      indirect test of pancreatic function presented unexplained pathologic values in 4
      out of 10 patients. In conclusion, we suggest that chronic asymptomatic elevation
      of pancreatic enzymes is of unknown etiology with no associated structural
      pancreatic pathology demonstrable by the usual study methods.

PMID- 9644873
TI  - [Endoscopic, histologic and morphometric evaluation of the gastric mucosa in
      patients with osteoarthritis treated with piroxicam and zinc acexamate].
AB  - Zinc acexamate (ZAM) is an antiulcer agent with antisecretory and
      gastroprotective properties. The aim of this study was to evaluate endoscopically
      and morphometrically the efficacy of ZAM in the prophylaxis of gastroduodenal
      lesions induced by pyroxicam. Thirty nine patients from 30 to 70 years of age
      diagnosed with osteoarthritis without lesions in the upper digestive tract on
      basal endoscopy were studied. A randomized, double blind study was designed in
      which the patients received 20 mg/day of pyroxicam together with 300 mg/day of
      ZAM or placebo for 4 weeks. Clinical controls were undertaken on days 0, 14, 28
      and endoscopic and histologic controls performed on days 0 and 28. The two groups
      were homogeneous regarding basal parameters. Endoscopic grading of the
      gastroduodenal lesions at the end of the study was lower in the group treated
      with ZAM (p < 0.001). Ulcers were found in only 2 patients (one antral and one
      duodenal) both of whom were in the placebo group (10.5%). Histologic scoring
      following treatment demonstrated higher values in the placebo group (p < 0.001)
      and scarce alterations with respect to base values in the group treated with ZAM.
      Morphometric quantification showed lower cell densities in both groups at the
      body level (p < 0.001). However, these did not vary in the antrum in the group
      treated with ZAM but increased in the placebo group (p < 0.001) as an expression
      of proliferative cell response to mucosal damage. At a single nightly dosis of
      300 mg ZAM is effective in the prophylaxis of gastric and duodenal lesions
      induced by pyroxicam.

PMID- 9644874
TI  - [Resection as elective treatment of hilar cholangiocarcinoma (Klatskin tumor)].
AB  - A retrospective analysis of our experience in the treatment of hiliary
      cholangiocarcinoma or Klatskin tumor was performed with the aim of evaluating the
      morbi-mortality and prognosis of its treatment to thereby determine the
      usefulness of the different therapeutic options. From 1989 to 1997, 51 patients
      diagnosed with hiliary cholangiocarcinoma were treated in our hospital. Surgery
      was indicated in 16 with curative aims (group I) while palliative treatment with
      percutaneous biliary drainage was indicated in 35 (group II). Biliary resection
      was carried out in 8 patients being associated with hepatic resection in 4 (group
      IA) and in 8 patients undergoing liver transplantation (group IB). Clinico
      epidemiologic data and hospital stay were similar in all the groups. The
      frequency of complications was similar in groups I and II although the frequency
      of cholangitis (49%) in group II was noticeable. The percentage of readmissions
      was also greater in group II (12 vs 46%, respectively; p = 0.03) with prosthesis
      obstruction being the most frequent cause. Accumulated survival at 1, 2, and 3
      years in group I was 84, 64 and 48% with a median survival of 33 months, while in
      group II the median survival was of 6 months with no patient surviving more than
      2 years (p = 0.0001). When groups IA and IB were compared, greater frequency of
      complications in groups IA (100 vs 37%; p = 0.002), similar frequency of
      readmissions (87 vs 75%; p = NS), median survival greater in group IB (12.5
      months vs 48 months) and significantly higher actuarial survival in group IB (48%
      in 2 years vs 83% to 2 years; p = 0.02) was observed. In conclusion, surgery is
      the treatment of choice in hiliary cholangiocarcinoma whenever possible, given
      the greater survival without a significant increase in morbimortality. Likewise,
      we consider that liver transplantation is a useful option in the treatment of
      patients with cholangiocarcinoma type IV of Bismuth.

PMID- 9644875
TI  - [Endometriosis: an infrequent cause of colonic obstruction].
AB  - Endometriosis localized in the intestinal wall is not an infrequent finding.
      Diagnosis is difficult given the diverse symptomatology presented with unspecific
      abdominal pain being the most common. Implantation of endometrial tissue in the
      intestinal wall may involve the mucosa and present as rectorhagia, with
      colonscopic exploration providing diagnosis by biopsy of the affected area. In
      other cases this may only involve the intestinal wall producing very varied
      symptomatology. Presentation as a picture of colon obstruction is little
      reported. The main problem is its difficult differential diagnosis with neoplasm
      which, in most cases, leads to surgery. A case of colon obstruction provoked by
      implantation of endometrial tissue in the wall of the sigma which was surgically
      resolved is herein presented.

PMID- 9644876
TI  - [Hydatid cyst in the hepatic hilum causing a cavernous transformation in the
      portal vein].
AB  - Portal cavernomatosis consists in the substitution of the portal vein by many
      fine, twisting venules leading to the liver. This phenomenon is produced as a
      consequence of anterior thrombosis of the portal vein and is associated with
      chronic pancreatitis, cancer of the pancreas, intraabdominal sepsis and
      cholelithiasis. The symptomatology may be nul or present as obstructive jaundice
      or portal hypertension. Diagnosis is made by Doppler echography. The treatment is
      portal shunt when symptomatology is produced. In patients with cholelithiasis
      requiring surgery, the shunt is advised prior to biliary surgery since
      perioperative hemorrhage, if present, may be incoercible as in the case herein
      described. We present a 84-year-old woman with portal cavernomatosis the etiology
      of which was a hydatidic cyst located in the hepatic bifurcation and treated with
      mebendazol 10 years previously. This etiology has not been previously reported.

PMID- 9644877
TI  - [Abdominal pain and ascites as manifestations of hereditary angioneurotic edema].
AB  - Hereditary angioneurotic edema (HAE) is an infrequent autosomal dominant disorder
      characterized by a decrease in the levels or a dysfunction of the complement C1
      inhibitor factor (C1 inh). The clinical presentation varies widely and involves
      any area of the organism. Gastrointestinal involvement is usually as abdominal
      pain and may be accompanied by ascites. De novo diagnosis of HAE with abdominal
      pain and ascites as a form of presentation is difficult with differential
      diagnosis with abdominal pain of unknown origin. The appearance of ascites is
      rare with few cases reported in the literature. Both abdominal pain and ascites
      disappear a few days after initiation of medical treatment. Occasionally
      exploratory laparotomy has been required. A new case of abdominal pain and
      ascites as manifestations of HAE is herein reported.

PMID- 9644878
TI  - [A case of non Hodgkin Lymphoma in a patient with hepatic cirrhosis by the
      hepatitis C virus].
AB  - We present a case of non-Hodgkin's lymphoma of B cells in a patient with
      cirrhosis by hepatitis C virus. Our patient presented scarce symptomatology
      related with non-Hodgkin's lymphoma. A notable hyperbilirrubinaemia with
      hypoalbuminaemia were the only features that allowed us to suspect the diagnosis.
      The diagnostic was proved by necroscopic study. There are several factors
      involved in the etiology of non-Hodgkin's lymphoma, including infectious agents.
      Recent Italian studies have suggested an association between C virus infection
      and non-Hodgkin's lymphoma. We have carried out a bibliographical revision of
      this association to conclude that important geographical differencies must be
      pointed out.

PMID- 9644879
TI  - [Pregnancy and intestinal inflammatory disease].

PMID- 9644881
TI  - [Enteral nutrition in gastrointestinal disease].

PMID- 9644880
TI  - [Collagenous colitis].

PMID- 9644882
TI  - [Topical nitroglycerin in the treatment of anal fissure].

PMID- 9644883
TI  - [Gastric adenocarcinoma and kidney transplantation].

PMID- 9644884
TI  - [The prevalence of hepatitis C virus infection].

PMID- 9644885
TI  - [Symptomatic recurrent or episodic fever of unknown origin in adenocarcinoma of
      the colon].

PMID- 9644886
TI  - [Gastric carcinoma with squamous differentiation].

PMID- 9644887
TI  - [Differences in pharmaceutical products of omeprazole].

PMID- 9644888
TI  - [Differences in pharmaceutical products of omeprazole].

PMID- 9644889
TI  - An adaptive backpropagation neural network for real-time ischemia episodes
      detection: development and performance analysis using the European ST-T database.
AB  - A supervised neural network (NN)-based algorithm was used for automated detection
      of ischemic episodes resulting from ST segment elevation or depression. The
      performance of the method was measured using the European ST-T database. In
      particular, the performance was measured in terms of beat-by-beat ischemia
      detection and in terms of the detection of ischemic episodes. The algorithm used
      to train the NN was an adaptive backpropagation (BP) algorithm. This algorithm
      drastically reduces training time (tenfold decrease in our case) when compared to
      the classical BP algorithm. The recall phase of the NN is then extremely fast, a
      fact that makes it appropriate for real-time detection of ischemic episodes. The
      resulting NN is capable of detecting ischemia independent of the lead used. It
      was found that the average ischemia episode detection sensitivity is 88.62% while
      the ischemia duration sensitivity is 72.22%. The results show that NN can be used
      in electrocardiogram (ECG) processing in cases where fast and reliable detection
      of ischemic episodes is desired as in the case of critical care units (CCU's).

PMID- 9644890
TI  - Spatial filtering and neocortical dynamics: estimates of EEG coherence.
AB  - The spatial statistics of scalp electroencephalogram (EEG) are usually presented
      as coherence in individual frequency bands. These coherences result both from
      correlations among neocortical sources and volume conduction through the tissues
      of the head. The scalp EEG is spatially low-pass filtered by the poorly
      conducting skull, introducing artificial correlation between the electrodes. A
      four concentric spheres (brain, CSF, skull, and scalp) model of the head and
      stochastic field theory are used here to derive an analytic estimate of the
      coherence at scalp electrodes due to volume conduction of uncorrelated source
      activity, predicting that electrodes within 10-12 cm can appear correlated. The
      surface Laplacian estimate of cortical surface potentials spatially bandpass
      filters the scalp potentials reducing this artificial coherence due to volume
      conduction. Examination of EEG data confirms that the coherence estimates from
      raw scalp potentials and Laplacians are sensitive to different spatial bandwidths
      and should be used in parallel in studies of neocortical dynamic function.

PMID- 9644891
TI  - Differential characterization of neural sources with the bimodal truncated SVD
      pseudo-inverse for EEG and MEG measurements.
AB  - A method for obtaining a practical inverse for the distribution of neural
      activity in the human cerebral cortex is developed for electric, magnetic, and
      bimodal data to exploit their complementary aspects. Intracellular current is
      represented by current dipoles uniformly distributed on two parallel sulci joined
      by a gyrus. Linear systems of equations relate electric, magnetic, and bimodal
      data to unknown dipole moments. The corresponding lead-field matrices are
      characterized by singular value decomposition (SVD). The optimal reference
      electrode location for electric data is chosen on the basis of the decay behavior
      of the singular values. The singular values of these matrices show better decay
      behavior with increasing number of measurements, however, that property is useful
      depending on the noise in the measurements. The truncated SVD pseudo-inverse is
      used to control noise artifacts in the reconstructed images. Simulations for
      single-dipole sources at different depths reveal the relative contributions of
      electric and magnetic measures. For realistic noise levels the performance of
      both unimodal and bimodal systems do not improve with an increase in the number
      of measurements beyond approximately 100. Bimodal image reconstructions are
      generally superior to unimodal ones in finding the center of activity.

PMID- 9644892
TI  - Adaptive canceling of physiological tremor for improved precision in
      microsurgery.
AB  - Physiological hand tremor impedes microsurgery. We present both a novel adaptive
      algorithm for tremor estimation and a new technique for active real-time
      canceling of physiological tremor. Tremor is modeled online using the weighted
      frequency Fourier linear combiner (WFLC). This adaptive algorithm models tremor
      as a modulating sinusoid, and tracks its frequency, amplitude, and phase.
      Piezoelectric actuators move the surgical instrument tip in opposition to the
      motion of tremor, effectively subtracting the tremor from the total motion. We
      demonstrate the technique in one dimension using a cantilever apparatus as a
      benchtop simulation of the surgical instrument. Actual hand motion, prerecorded
      during simulated surgery, is used as input. In 25 tests, WFLC tremor compensation
      reduces the rms tip motion in the 6-16 Hz tremor band by 67%, and reduces the rms
      error with respect to an a posteriori estimate of voluntary motion by 30%. The
      technique can be implemented in a hand-held microsurgical instrument.

PMID- 9644893
TI  - Simulation of depolarization in a membrane-equations-based model of the
      anisotropic ventricle.
AB  - The results of a simulation study of the propagation of depolarization in
      inhomogeneous anisotropic (monodomain) myocardial tissue are presented.
      Simulations are based on modified Beeler-Reuter membrane equations, and performed
      on a block of anisotropic myocardium with rotating fiber geometry, measuring 1 cm
      x 1 cm x 0.3 cm, at various levels of spatial discretization (0.15 mm, 0.30 mm,
      0.60 mm). At a discretization level of 0.6 mm the algorithm allowed the
      simulation in a realistically shaped model of the ventricle, including rotational
      anisotropy, as well. For this simulation results are justified by comparing
      results for the block at various levels of discretization, for which the surface
      to volume ratio has been adjusted. By placing the model ventricle in a
      realistically shaped (human) volume conductor model, realistic body surface
      potentials (QRST waveforms) are simulated.

PMID- 9644894
TI  - Biological cells with gap junctions in low-frequency electric fields.
AB  - Biological effects have been observed from weak, low-frequency magnetic fields.
      It has been suggested that the observed effects are due to the induced currents
      and electric fields. The behavior of cells exposed to an electric field is
      investigated in this paper. The induced transmembrane potential (TMP) is examined
      in geometrically complex models of various cell configurations. The TMP is
      evaluated using the finite element method (FEM), a numerical technique that is
      well suited to complicated geometries. Because displacement currents can be
      neglected at very low frequencies, a FEM solver that considers only material
      conductivity is used. Therefore, our results apply only well below the relaxation
      frequency. Chains and clusters of gap-connected cells of various sizes are
      modeled. The conductivity and size of the gap junctions in the cell
      configurations are also varied. The results for small configurations are compared
      to models of ellipsoidal cells with shapes similar to those of the
      configurations. FEM estimates of TMP's in long, cylindrical cell chains are
      compared to the predictions of the leaky cable model. The FEM approach confirms
      that gap-junction-connected cells can be treated as a single similarly shaped
      cell. Gaps influence the potential in the interior of cell configurations, and
      these effects increase with gap size and conductivity. For configurations to
      which approximations such as the leaky cable model do not apply, the FEM approach
      can be used to estimate the TMP, if the model is adapted to fit within
      computational memory limits.

PMID- 9644895
TI  - A study of printed spiral coils for neuroprosthetic transcranial telemetry
      applications.
AB  - We have explored the use of printed spiral coils (PSC's) for neuroprosthetic
      transcranial telemetry applications. We fabricated two-dimensional PSC's on a
      thin (25 microns) polyimide substrate using copper (35 microns) as a conducting
      material. All the coils had a fixed inner diameter of 1.0 cm. We fabricated two
      sets of coils. One set of coils consisted of 2- to 5-turn circular and square
      spiral coils and had different trace widths (W), different spacings (S) between
      adjacent traces, and different outer diameters. The other set of coils consisted
      of 5-turn circular spiral coils and had fixed inner and outer diameters but
      different W to S ratios. We measured loss resistances (Rs and Rp) and quality
      factors (Q) of these coils at different resonating frequencies in the range of 5
      40 MHz. Over this frequency range, we observed that for fixed inner and outer
      diameters, the coil with the largest W achieved the lowest Rs and the highest Rp
      and Q. These electrical properties and the fact that these coils can conform to
      the complex convoluted cortical surface suggest that a PSC [15] can provide a
      viable alternative to a conventional wire-wound coil for neuroprosthetic
      transcranial telemetry applications.

PMID- 9644896
TI  - Geometric effects on resistivity measurements with four-electrode probes in
      isotropic and anisotropic tissues.
AB  - We studied via computer simulation the effects of electrode diameter, electrode
      length, interelectrode spacing, and tissue size on the accuracy of measured
      tissue resistivities and anisotropy ratios obtained with the widely used four
      electrode technique. Such measurements commonly assume an ideal situation in
      which the four electrodes are infinitesimally small and the tissue is semi
      infinite. Our study shows that these geometric factors can significantly affect
      measured resistivities, particularly for anisotropic tissues. The measured
      anisotropy ratio is decreased by either 1) increasing the electrode diameter or
      length relative to the interelectrode spacing of the probe or 2) decreasing
      tissue size. We have provided an equation for estimating errors in the measured
      anisotropy ratio from the parameters of electrode and tissue geometries. The
      simulation findings are supported by our in vitro experimental results.

PMID- 9644897
TI  - Microwave catheter design.
AB  - A microwave antenna system for transcatheter ablation of cardiac tissue is
      investigated. A numerical model based on the finite-difference time-domain method
      incorporating a Gaussian pulse excitation has been constructed and frequency
      domain electric and magnetic fields are obtained through Fourier transformation.
      Results are presented for a coaxial line fed monopole catheter which is modified
      by the successive inclusion of a Teflon sheath outer coating, a terminating disk
      at the tip of the antenna, a sleeve choke, and a high dielectric constant
      cylinder surrounding the monopole antenna. The effects of these design features
      are characterized in terms of specific absorption rate (SAR) and return loss
      (RL). Numerical calculations are confirmed by comparing with the RL measurement
      of a Teflon-coated monopole containing a disk and choke.

PMID- 9644898
TI  - Microfabricated cantilevers for measurement of subcellular and molecular forces.
AB  - We present two new microfabricated cantilever-beam force transducers. The
      transducers were fabricated from thin silicon-nitride films, and were used
      respectively to measure forces generated by two small-muscle preparations: the
      single myofibril, and the single actin filament in contact with a myosin-coated
      surface. A simple resonance method was developed to characterize the transducers.
      Because of the high reproducibility of lever dimensions and the consistency of
      the modulus of elasticity, few calibration measurements sufficed to characterize
      the stiffness of all the levers on a single wafer.

PMID- 9644899
TI  - An iterative Newton-Raphson method to solve the inverse admittivity problem.
AB  - By applying electrical currents to the exterior of a body using electrodes and
      measuring the voltages developed on these electrodes, it is possible to
      reconstruct the electrical properties inside the body. This technique is known as
      electrical impedance tomography. The problem is nonlinear and ill conditioned
      meaning that a large perturbation in the electrical properties far away from the
      electrodes produces a small voltage change on the boundary of the body. This
      paper describes an iterative reconstruction algorithm that yields approximate
      solutions of the inverse admittivity problem in two dimensions. By performing
      multiple iterations, errors in the conductivity and permittivity reconstructions
      that result from a linearized solution to the problem are decreased. A finite
      element forward-solver, which predicts voltages on the boundary of the body given
      knowledge of the applied current on the boundary and the electrical properties
      within the body, is required at each step of the reconstruction algorithm.
      Reconstructions generated from numerical data are presented that demonstrate the
      capabilities of this algorithm.

PMID- 9644900
TI  - Optimization of the deposited power distribution inside a layered lossy medium
      irradiated by a coupled system of concentrically placed waveguide applicators.
AB  - A method is proposed for controlling the deposited power distribution in a
      layered cylindrical lossy model, irradiated by a phased-array hyperthermia system
      consisting of four waveguide applicators. A rigorous electromagnetic model of the
      heated tissue, which takes into account coupling phenomena between system
      elements, is used for predicting the electric field at any point inside tissue.
      The relative amplitudes and relative phases of the array elements are optimized
      in order to attain desired specific absorption rate (SAR) distributions inside
      and outside malignant tissues. A constrained nonlinear optimization problem is
      solved by using the penalty function method and the resulting unconstrained
      minimization of the penalty function is carried out by the downhill simplex
      method. Two practical phased-array hyperthermia systems have been studied and
      numerical results are presented.

PMID- 9644902
TI  - Multipolar laminated electromagnet for low-field magnetic resonance imaging and
      electron paramagnetic resonance imaging.
AB  - A cylindrical 16-pole electromagnet (EM) for electron paramagnetic resonance
      imaging (EPRI) and low-field magnetic resonance imaging (MRI) has been designed
      by means of two-dimensional and three-dimensional (3-D) finite element analysis
      (FEA). The use of an automatic procedure that combines FEA with a minimization
      routine allowed the optimization of the design, in order to improve the
      homogeneity along the axis of the EM. A prototype has been built by using
      electrical steel sheets that were cut by laser; this solution reduced
      significantly the manufacturing cost. The EM operates with a maximum flux
      density, in the bore, of 0.08 T and has a homogeneity along the axis of about 40
      parts per million (ppm) in a spherical region 10 cm in diameter. It generates the
      main field and two of the three field gradients required in the 3-D image
      reconstruction. Good agreement was found between the results of simulation and
      the measured values.

PMID- 9644901
TI  - Measuring the progression of foreign-body reaction to silicone implants using in
      vivo MR microscopy.
AB  - We used in vivo magnetic resonance (MR) microscopy to follow the growth of
      fibrous capsule as a foreign body reaction to silicone implants in rats.
      Anesthetized rats were imaged 1, 7, 14, and 28 days after silicone-coated MR
      imaging coils were sutured to their neck muscles. On the twenty-eighth day, rats
      were sacrificed and coils and adjacent tissues were removed en bloc and fixed in
      formalin, reimaged with MR, and sectioned for conventional histology. Three
      dimensional (3-D) spin-echo [3DFT] acquisition gave in-plane resolution of 32 x
      32 microns in vivo and 16 x 16 microns ex vivo. All MR images showed a diffuse
      band of elevated signal intensity between the silicone of the coil and adjacent
      tissue. The border of the hyperintense band was thin and not well defined at
      seven days post-implantation. From 7-28 days, the band showed relatively
      homogeneous signal intensity and its thickness increased 44% on the rectus muscle
      side and 78% on the subcutaneous side. The capsule thickness determined either by
      MR in vivo and ex vivo microscopy or conventional histology was not significantly
      different, and there was a significant correlation between thickness measurements
      among those methods. MR in vivo microscopy provides sufficient resolution and
      spatial information to serially evaluate the growth of the foreign body fibrous
      capsule over time, thus achieving greater accuracy and consistency in
      measurements.

PMID- 9644903
TI  - A comparative study of human skin thermal response to sapphire contact and
      cryogen spray cooling.
AB  - Surface cooling, in conjunction with various thermally mediated therapeutic
      procedures, can provide a means to protect superficial tissues from injury while
      achieving destruction of deeper targeted structures. We have investigated the
      thermal response of in-vivo human skin to: 1) contact cooling with a sapphire
      window (6-12 degrees C); and 2) spray cooling with a freon substitute cryogen
      [tetrafluoroethane; boiling point approximately -26 degrees C at 1 atmospheric
      pressure (atm)]. Measurements utilizing infrared radiometry show surface
      temperature reductions from 30 degrees C to 14-19 degrees C are obtained within
      approximately 1 s in response to sapphire contact cooling. Surface temperature
      reductions to values between 5 degrees C and -9 degrees C are obtained in
      response to 20-100-ms cryogen spurts. Computational results, based on fitting the
      measured radiometric surface temperature to estimate heat transfer parameters,
      show: 1) temperature reductions remain localized to approximately 200 microns of
      superficial tissue; and 2) values of heat flux and total energy removed per unit
      skin surface area at least doubled when using cryogen spray cooling.

PMID- 9644904
TI  - KLT-based quality controlled compression of single-lead ECG.
AB  - An electrocardiogram (ECG) compression algorithm based on a combination of the
      Karhunen-Loeve transform (KLT) and multirate sampling is introduced. The use of
      multirate sampling reduces KLT computational times to those reported for wavelet
      packet-based compression techniques. A beat-by-beat quality controlled
      compression criterion is shown to be necessary to ensure clinically adequate
      reconstruction of each beat. The resulting quality controlled algorithm
      efficiently achieves compression rates of approximately 30-40:1 for the MIT-BIH
      database.

PMID- 9644905
TI  - A simple design methodology for elliptical cross-section, transverse, asymmetric,
      head gradient coils for MRI.
AB  - A simple design process for the design of elliptical cross-section, transverse
      gradient coils for use in magnetic resonance imaging (MRI) is presented. This
      process is based on a flexible stochastic optimization method and results in
      designs of high linearity and efficiency with low switching times. A design study
      of a shielded, transverse asymmetric elliptical coil set for use in neural
      imaging is presented and includes the minimization of the torques experienced by
      the gradient set.

PMID- 9644906
TI  - [Heat barriers in progressive evolution of animals and humans].
AB  - The principle of fastest descent in thermodynamics of nonequilbrium processes is
      a physical foundation of progressive evolution of animals and humans. We present
      a curve of bioenergetic progress of animals and demonstrate that movement along
      this curve form a certain moment is only possible if "the first heat barrier" is
      overcome, which corresponds to the intensity of animal respiration (coefficient a
      5-6 mWt/g). Overcoming this barrier is related to the development of
      thermoregulation and appearance of homoiothermic animals. "The second heat
      barrier" (coefficient a about 45-50 mWt/g) is related to heating of the animal
      body up to the damaging temperatures and this barrier is overcome as a result of
      conscious activity and the appearance of human civilization. The possibility of
      "the third heat barrier" is discussed as a result of energy production by
      industry. Overcoming of "the third heat barrier" is possible through assimilation
      of the space and transfer in the space of energy-producing industry.

PMID- 9644907
TI  - [The nature of the circahoralian (ultradian) intracellular rhythms. Similarity to
      fractals].
AB  - The properties and possible origin of circahoralian intracellular rhythms are
      discussed. Irregularity of these oscillations, as expressed in different time
      scales, determination, and resistance to external influences, including changes
      in the environmental temperature, are noted. No pacemaker of circahoralian
      rhythms was found. These specific features and analysis of the structure of
      circahoralian rhythms (Herst equation) suggest their similarity to fractals,
      chaotic but determined forms with a certain internal structure. Determination of
      circahoralian rhythms in a cell-free system and their possible fractal nature
      characterizes the rhythms as an imminent property of the cytoplasm, that does not
      require special regulation. Modulations of the frequency and amplitude of
      oscillation under the influence of external influences are described. It is
      proposed that the circahoralian rhythms are a protective factor for the cell and
      organ functions and a mechanism of adaptations under varying life conditions.

PMID- 9644908
TI  - [Regulation of myogenesis].
AB  - Molecular-biological and molecular-genetic mechanisms underlying regulation of
      muscle formation were analyzed from the earliest stages of commitment and
      determination of myogenic precursors to the terminal stages of muscle
      differentiation. It was shown how inductive influences of the neural tube and
      notochord on the somites leading to formation of myotomes are related to
      expression of genes of the Shh and Wnt families. Differentiation of proliferating
      myoblasts and myotubes is related to expression of the genes encoding synthesis
      of bHLH proteins: MyoD and Myf5 in the myoblasts and myogenin and MRF4 in the
      myotubes. The products of these genes are transcription factors and control the
      subsequent stages of myogenesis, specifically, myogenin controls expression of
      the genes of contractile proteins. Changes in the spectra of contractile proteins
      during ontogenesis and diversity of their isoforms are related both to the
      expression of various genes and to their alternative splicing. The mechanisms
      underlying the assembly of myofibrils in ontogenesis, which involve, in addition
      to myosin and actin, proteins of Z-bands and A-discs, were analyzed.

PMID- 9644909
TI  - [Flocculation of bacterial cells in culture with protozoa].
AB  - The initial phase of formation of the biogenic suspension was studied in
      experimental communities of bacteria and protozoans that simulate degradation of
      the phenol technogenic flows. Protozoans were shown to initiate formation of
      bacterial aggregates and increase the size of bacterial flocules several hundred
      times. Factors were found by the methods of mathematical planning, which markedly
      affect the size and amount of flocules. Unlike natural water bodies, in the
      sample communities, the presence of abiogenic substrate was not essential for
      aggregation of the bacteria. The aggregated bacterial cells make an important
      contribution to degradation of organic compounds.

PMID- 9644910
TI  - [Response of adult djungarian hamsters (Phodopus sungorus) to odor signals of
      species of their own and opposite sex during different seasons with the reference
      to reproduction process].
AB  - Studies were carried out on adult Djungarian hamster (Phodopus sungorus) males
      living in familial pairs under natural thermal and light regimes year-round. The
      response of hamsters to the odors of urine, secretory substances of the
      midabdominal gland and additional saccules in the ostium of cheek pouches, and
      faeces from conspecific males and females were studied. The results obtained
      suggest that the odors of urine and also feces play an important role in sexual
      recognition of individuals. These odors are especially attractive for the males
      in summer, during the period of active breeding. The tested males examined the
      odor of the midabdominal gland from individuals of the same sex reliably longer
      throughout the year, but in winter the interest in this odor was higher than in
      summer. These secretory substances appear to be important in organization of
      territorial interactions between individuals. The results of observations on
      breeding and the data on sex ratio in the broods from pairs with the tested males
      were compared to similar data obtained earlier for Roborovskii hamsters (Sokolov
      and Feoktistova, 1996). Similarities and differences were found in the course of
      breeding in the studied species.

PMID- 9644911
TI  - [Strategy of small rodent populations from Kanev national park under habitat
      changes caused by technogenic pollutions and an accident at the Chernobyl nuclear
      power station].
AB  - The results of a long-term investigation are provided, which permit us to
      evaluate the problem of population adaptation to qualitative habitat changes due
      to the accident at the Chernobyl nuclear power station from a new standpoint. We
      note the specific response of various species, the disturbed ecological balance,
      and a slowing of the "population clock" and biotic cycle.

PMID- 9644912
TI  - [Anticoagulant and fibrinolytic effects of proline-containing peptides].
AB  - Anticoagulant, fibrinolytic, and fibrin-depolymerization effects were revealed
      during in vitro study of five proline-containing peptides (Gly-Pro, Trp-Pro, Pro
      Gly, Gly-Pro-Gly-Gly, and Pro-Gly-Pro) in the concentration range 10(-9) to 10(
      1) mg/ml. Intravenous injection of Trp-Pro and Pro-Gly into white rats at 250
      micrograms/kg body weight significantly increased recalcification time and
      activated partial thromboplastin time of serum coagulation, increased
      fibrinolytic activity, decreased the level of serum factor XIII/(/)a and
      fibrinogen, and reduced thrombocyte aggregation. We propose inhibition of
      thromboplastin and thrombin formation in the serum by the studied proline
      containing peptides both in vitro and in vivo.

PMID- 9644913
TI  - [Response of the isolated muscle tissue of frog species to the successive effects
      of subtoxic and toxic chloral hydrate solutions].
AB  - Time-related changes in the mean resistance of sartorius muscle from individual
      common frogs to the toxic effect of chloral hydrate (0.05 and 0.08 M) were
      observed. The correlation coefficient between the initial muscle resistance and
      the value and direction of its changes as well as between the resistance of the
      paired muscle under the influence of subtoxic chloral hydrate solution (0.005 M)
      was calculated. A biphase pattern of change of almost all the above indices
      depending on the dose of pretreatment was observed. Time-related changes in the
      correlation coefficient between muscle resistance and its changes and between the
      resistance of the paired muscle and variability of the resistance proved to be
      much more informative than the mean resistance concerning both the muscle
      response to the stimulus and functional state of the muscle cells.

PMID- 9644914
TI  - [Study of amphibian brain asymmetry during normal embryonic and larval
      development].
AB  - Amphibian embryos (Triturus vulgaris, Pleurodeles waltl, Hynobius keyserlingii,
      Ambystoma mexicanum, Rana temporaria, Bufo bufo, and Xenopus laevis) were
      investigated. We ascertained the morphological right-side asymmetry of the brain,
      which appears at the neurula stage and is preserved during the postembryonic
      (larval) development. In T. vulgaris, P. waltl, H. keyserlingii, and X. laevis,
      we observed right-side asymmetry of peripheral analyzers, such as the retina,
      ganglia of nerve VIII, and olfactory placodes. Structural analysis of the
      forebrain in A. mexicanum has shown that in the larvae, the pallium prevails on
      the left side of the cerebral hemisphere. During metamorphosis, left-side
      asymmetry is replaced by right-side, which is then preserved. We propose that the
      brain asymmetry arose at the early stages of evolution as a result of embryonic
      formation of the nervous system.

PMID- 9644915
TI  - [Pathogenesis and laboratory diagnosis of diabetic nephropathy (literature
      review)].

PMID- 9644916
TI  - [Evaluation of the reserve potential of the blood kallikrein-kinin system in
      healthy subjects].
AB  - The reserve potential of the blood kinin-producing activity and kallikrein
      inhibitors were assessed under conditions of a functional test (double local
      hypoxia of the upper limb) in 68 healthy volunteers aged 17-45 years. Three types
      of reactions of the studied components of the kallikrein-kinin system (KKS) were
      distinguished: concomitant (79.4%), kininase (5.9%), and kininogenesis (14.7%).
      The concomitant type was characterized by increased activity of all components of
      the system during the test, indicating its sufficient reserve potential. A drop
      of kinin production and increased activity of the inhibitory component of KKS in
      response to hypoxia reflect a low reserve potential of kininogenesis in subjects
      with the kininase type of KKS. An appreciable decrease of kallikrein inhibitor
      activity during the test in the presence of increased kininogenesis demonstrates
      the limited reserves of the inhibitory component of the kinin cascade in normal
      subjects with the kininogenesis type of KKS.

PMID- 9644917
TI  - [Laboratory criteria of ejaculate fertility (literature review)].

PMID- 9644918
TI  - [The effect of laser radiation on the seminal fluid in man].
AB  - The effect of low-intensive laser with a wavelength of 0.63 micron on human
      seminal fluid is studied. Seminal fluids of different groups distinguished
      according to spermogram values differently react to laser exposure. Experimental
      studies demonstrated both stimulating and destructive effects of laser on human
      seminal fluid.

PMID- 9644919
TI  - [Differential diagnosis of hematuria on the basis of morphology of stained
      erythrocytes].
AB  - Glomerular and nonglomerular hematuria was differentiated in 40 patients by the
      morphology of erythrocytes stained with floxin in buffer solution. Glomerular
      hematuria was correctly diagnosed in 91.0%, nonglomerular in 88.9% of patients.
      The results of diagnosis of hematuria by floxin staining and by phase-contrast
      microscopy coincided; both methods are superior to the Right staining technique.
      The proposed method is easily available for any laboratory and is suggested for
      tentative diagnosis, in order to improve the diagnostic process.

PMID- 9644920
TI  - [Detection of chlamydial infection by indirect cytological signs].
AB  - The author compares the efficacy of detecting chlamydial infection by the
      following methods: morphocytological analysis of urogenital smears under light
      microscope by indirect signs, such as 1) neutrophil histiocyte macrophagal
      reaction; 2) lymphoid infiltration with the presence of young forms; 3) basal
      cell hyperactivity with dysplasia; 4) proliferation of the cylindrical epithelium
      with dysplasia, and 5) dystrophic changes in the epithelium; detection of
      chlamydial antigen by immunofluorescence and enzyme immunoassay; and detection of
      specific antibodies. A total of 240 patients were examined at the Regional Family
      Planning Center (163 women and 43 men of fertile age and 34 children and
      adolescents). Chlamydial origin of inflammation suspected from the above
      cytomorphological signs in 208 (87%) patients was confirmed by virological
      studies: chlamydial antigen was detected in 67% and specific antibodies in
      diagnostic titers in 20% of patients. This latter group was administered a course
      of specific antichlamydial therapy after detection of chlamydial antigen. The
      author concludes that patients with morphocytological signs of chronic
      inflammation listed above detected in the urogenital smears should be referred to
      a group at risk of chlamydiasis. The proposed method of screening is rapid,
      economic, and easily available.

PMID- 9644921
TI  - [Adhesiveness of peripheral blood neutrophils in normal subjects and in cancer
      patients].
AB  - A spectrophotometric method for assessing the capacity of phagocytes to adhere to
      the plastic is proposed. The method consists in staining a cell monolayer after
      Romanovsky-Giemsa in the wells of a 96-well flat-bottom plate, extraction of the
      stain, and assessment of the optic density of this solution at 650 nm. Methods
      for obtaining the cells in leukocyte concentrate (LC) and neutrophil suspension
      (NS) obtained in the density gradient are described. Two calibration curves for
      LC and NS are plotted for assessing the correspondence between optic density and
      a certain number of adhesive neutrophils. There were no statistical differences
      between the two curves. Neutrophil adhesion parameters of 38 donors are
      presented. The adhesive capacity of blood neutrophils is decreased in cancer
      patients (in 25 out of 27).

PMID- 9644922
TI  - [Cytological diagnosis of thyroid cancer in a child using puncture biopsy of the
      cervical lymph node].

PMID- 9644923
TI  - [Osteoporosis: diagnosis of disorders of bone tissue and calcium-phosphorus
      metabolism (lecture)].
AB  - Tentative diagnoses of lymphadenitis or Hodgkin's disease were not confirmed in a
      12-year-old child by cytological investigations. Along with lymphoid cells,
      individual leukocytes, histiocytes, macrophages, and glandular cancer cells, the
      cytological preparation of the cervical lymph node biopsy specimen contained
      uncommon multinuclear cells looking like interfollicular thyroid islets. This
      indicated cancer metastasis and the site of primary involvement: the thyroid. The
      diagnosis was confirmed by the histological and radionuclide methods.

PMID- 9644924
TI  - [Statistical estimation of the precision of clinico-laboratory measurements].
AB  - Traditionally, the term "precision" denotes the quality of work, uniting the
      correctness and reproducibility of results. However, it can have another sense:
      the minimal difference between the specimens, detectable by this or that device
      or method. In order to rule out misunderstanding, we propose to use the term
      "measuring precision", if the term is used in its second meaning. It is easy to
      assess the measuring precision by statistical processing of large scope of data:
      if the histogram shows waves which disappear after the histogram step is
      increased, this means that the device and method used in this study permit
      biochemical analysis only at measuring precision corresponding to the histogram
      step at which the waves disappear. A table of measuring precision values is
      offered for 19 methods realized using the Labsystems FP-900 device (Finland) In
      many cases it is obviously low.

PMID- 9644925
TI  - [Characteristics of the organization of clinical laboratory using modern
      hematological analyzers].
AB  - Large treatment and prophylaxis multiprofile centers should be equipped with
      several devices with different potentials. Rational use of the potentials of
      modern hematological analyzers requires use of venous blood samples. Complete
      hematological analyzers, such as Cobas Vega, can minimize visual assessment of
      the leukocytic formula. Effective clinical application of the entire complex of
      parameters offered by the analyzers and introduction of these devices in practice
      involve upgrading of all laboratory workers.

PMID- 9644926
TI  - [MEDLAB-97 (12th European Congress on Clinical Chemistry. Basel, Switzerland)].

PMID- 9644927
TI  - [Prions and neurodegenerative human diseases].

PMID- 9644928
TI  - [Role of molecular mechanisms regulating functions of glucocorticoid hormone
      receptors in pathogenesis and treatment of cardiovascular diseases].

PMID- 9644929
TI  - [New opportunities in diagnosis and treatment of gastroesophageal reflux and
      cardial achalasia (dedicated to 65th anniversary of professor A.L. Grebnev)].

PMID- 9644930
TI  - [Problems of osteoporosis: study of biochemical markers of bone metabolism].

PMID- 9644931
TI  - [Efficacy of ursodeoxycholic acid (UDCA) in the treatment of chronic alcoholic
      hepatitis].
AB  - Treatment for chronic alcoholic hepatitis with UDCA drug was performed in 76
      patients. In development of this kind of hepatitis an essential role belongs to
      defects in the systems of lipid peroxidation and antioxidant defense. The UDCA
      drug produced stabilization of cell membranes, changed bile composition by
      effects on bile acids pool and micellar complex. Clinicomorphological remission
      was available in 88% of cases.

PMID- 9644932
TI  - [Pericarditis: 5 year records of general hospital].
AB  - Among patients admitted to the therapeutic department of the general hospital for
      5 years, diagnosis of pericarditis was made in 110 patients (0.44%). Among the
      most common causes of secondary pericarditis were: chronic renal failure (31.8%),
      diffuse lesion of the connective tissue (17.7%), tumor metastases to the
      pericardium (15.5%). Primary pericarditis was, as a rule, of tuberculous
      etiology. Morphologically, it was adhesive or adhesive-exudative, constrictive,
      exudative in 13, 4.5 and 76% of patients, respectively. Half of the patients with
      exudative pericarditis had 300 to 800 ml of fluid in the pericardial cavity.
      Typical clinical manifestations were dyspnea and tachycardia. X-ray was
      diagnostically valuable in pericardial exudate 300 ml and more. ECG voltage fell
      in exudate more than 400-500 ml. Echocardiography remains an effective tool in
      diagnosis of pericarditis. The treatment consisted of antibiotics,
      antiinflammatory therapy, evacuation of the liquid from the pericardial cavity.

PMID- 9644933
TI  - [Differential diagnosis of neurocirculatory asthenia (NCA)].
AB  - 170 patients with primary diagnosis of NCA underwent detailed examination by the
      therapist, neuropathologist, endocrinologist, urologist, gynecologist and
      psychiatrist. Primary diagnosis was confirmed only in 47 patients, the other 123
      patients had different somatic, neurological or psychic disorders. These 47 and
      123 patients were considered as having NCA as a syndrome and as an independent
      nosological entity, respectively. NCA as a syndrome was associated with blood
      hypertension, nervous asthenia, ischemic heart disease, spinal osteochondrosis.
      One third of the patients had neuropsychic disorders. The conclusion is made that
      all the NCA patients require detailed therapeutic, neurological and psychic
      examinations to exclude hypertension, asthenoneurotic states, ischemic heart
      disease and spinal osteochondrosis.

PMID- 9644934
TI  - [Seasonal changes of secondary immunodeficiency in patients with vascular
      dystonia].
AB  - The examination of 60 patients with vascular dystonia (VD) and immunological
      disorders shows that secondary immunodeficiency is not a stable condition. It is
      associated with seasons of the year and VD variants. Secondary immunodeficiency
      is more pronounced in winter. A correlation exists between mixed vegetative
      vascular dystonia and combined T-lymphocyte secondary immunodeficiency in winter.
      The findings may help in planning immunotherapy in "critical seasons" for
      patients with vegetative disorders.

PMID- 9644935
TI  - [Nimotop: clinical spectrum].
AB  - This literature review concerns both well known facts on mechanisms of action of
      calcium channels blockers and less known effects on different systems of the
      body. In addition to vascular dilatation, the blockers produce neuroprotective
      action, promote dysaggregation. Detailed information is given on usage of soluble
      calcium antagonist-nimotop.

PMID- 9644937
TI  - [Noninvasive monitoring of arterial pressure in diagnosis and treatment of
      arterial hypertension].

PMID- 9644939
TI  - [Problem of heart insufficiency in the XIX European Cardiology Congress
      (Stockholm, August 1997)].

PMID- 9644938
TI  - [Crohn's disease of stomach].

PMID- 9644940
TI  - [International Chronobiology Congress].

PMID- 9644941
TI  - [The art of lecturing clinical medicine. Communication 1. Role of clinical
      lecture in physician's training].

PMID- 9644942
TI  - [Classification of chronic gastritis designed in Huston and its differences from
      sydney system].

PMID- 9644943
TI  - [Austrian reforms of university medical education in the second half of XVIII
      century. Communication 1. H.Van-Sviten's reforms of education at Vien university
      medical department].

PMID- 9644944
TI  - [Pharmacological modulation of the appetite].
AB  - The hypothalamus plays an essential role in the regulation of the body weight of
      all living creatures. In it there is a convergence of signals from the nervous
      system and signals from the peripheral tissues, through a complex system of
      neurotransmitters and neuropeptides. The ever increasing understanding of this
      field, opens up new therapeutic possibilities, both current and future, in the
      treatment of eating disorders.

PMID- 9644945
TI  - [L-carnitine levels in critical septic patients receiving parenteral nutrition].
AB  - Septicemia causes multiple and often not very well understood metabolic
      alterations. In this sense it is controversial whether or not carnitine is
      decreased, which may have several implications. Our objective is to measure the
      plasma carnitine levels in septicemic patients, and to find out whether this is
      modified if there is a multi-organ dysfunction syndrome (MODS), or if it is
      dependent on the lipid source. For this we carried out a prospective study in
      septicemic patients with MODS. These were given exclusively parenteral nutrition
      (PN) without any carnitine supplementation. The PN of 16 patients contained long
      chain triglycerides (LCT's), while that of another 12 contained a 1:1 mixture of
      long and medium chain triglycerides (LCT's and MCT's). We measured the plasma
      carnitine level at the baseline, after 5 days and after 10 days, using an
      enzymatic method that measures the total carnitine level (free and esterified).
      The normal values lie between 35 and 70 mumol/l. We included 28 septicemic
      patients whose ages were 53.41 +/- 16.51 years, and whose APACHE II on admission
      was 17 +/- 4. The carnitine levels were: baseline: 60.4 +/- 23.7; 5th day 57.7 +/
      22.9; 10th day 55.7 +/- 21.2 (p = n.s.). Of these patients, 10 had an MODS of
      septic origins with their baseline levels being: 65.3 +/- 30.9; 5th day 60.3 +/-
      23.2; 10th day 61.5 +/- 15.5; while the levels of the 18 septicemic patients
      without MODS, the baseline levels were 61.9 +/- 13.8; 5th day 58.6 +/- 19.1; 10th
      day 56.6 +/- 19.3 (p = n.s.). In the patients who were given LCT's the baseline
      carnitine level was 60.7 +/- 23.1, 5th day 60.1 +/- 23.8; 10th day 58.6 +/- 12.8;
      while those patients who were given LCT/MCT showed baseline levels of 64.3 +/-
      19.5; 5th day 58.6 +/- 19.1; 10th day 57.8 +/- 10.7 (p = n.s.). In our septicemic
      patients the serum carnitine levels we found were within the normal range, and
      these remained unchanged during the ten days in those patients with MODS or with
      the lipid mixture used.

PMID- 9644946
TI  - [Nutritional state of iron in the institutionalized aged: study of intake and
      hematological indices].
AB  - In this study we determined the nutritional state of iron in 93 elderly people
      who were institutionalized in Granada, by means of a determination of their
      ingested iron, as well as the determination of the serum iron, hematologic
      parameters (hemoglobin and hematocrit), and the corpuscular indexes (mean
      corpuscular volume and mean corpuscular hemoglobin). The elderly people had an
      iron intake that was considered to be adequate (10.2 +/- 2.1 mg/day), and this is
      not related to the hematological parameters studied. 4% of the men, and 22% of
      the women showed hemoglobin values that were considered to be low.

PMID- 9644947
TI  - [Weight and height of school children from the L'Horta region (Valencia)].
AB  - The growth and development of Valencian children from 6 to 14 years of age was
      studied using the weight and height of a representative sample (n = 2011) of
      school children in L'Horta de Valencia area. They represent 62% and 32.5% of the
      school population of the Valencia province and of the Comunidad Valenciana,
      respectively. The sample was proportional to the whole population in the
      geographical area and to sex and age. The measured children came from 10 schools,
      some of which were public and some private, drawn at random. After obtaining the
      permission from the school administrative board the measurements were taken,
      always by the same trained anthropometrist and with the same instruments, which
      were calibrated daily. The application of the Lilliefors test showed that the
      distribution of weight and height according to age was normal in the majority of
      the groups of age. Therefore, the Student t-test was applied to compare girls and
      boys, and given the fact that the symmetry was not complete in all age ranges,
      the results are expressed as percentiles. From 6 to 14 years girls and boys in
      Valencia show a similar weight evolution. Only in children in the highest
      percentiles, can be observed sex-related differences from the age of 12 on. In
      general, up to 13-14 years of age boys were slightly taller than girls of the
      same age. From this age on boys follow continue growing while girls stop their
      longitudinal growth.

PMID- 9644948
TI  - [Changes in feeding behavior of patients who had received enteral nutrition
      during the 1st year of life].
AB  - Enteral feedings delivered by either gastrostomy or a nasogastric tube are often
      used in infants and toddlers to ensure adequate caloric and nutrient intake. If
      we are not aware of a rapid introduction of oral feedings they may develop poor
      feeding skills. PATIENTS: Seven infants (mean age: 6.7 months; SD: 3.6) presented
      this problem during the 1993-96 period. Six of them were using a nasogastric
      tube, another one a gastrostomy (PEG). At the beginning of the enteral feeding
      regimen their weight was -3.32 z-score (SD: -1.2) and for height: -2.11 z-score
      (SD: -0.51). The underlying disease was gastroesophageal reflux (n = 4),
      esophageal atresia (n = 1), short bowel syndrome (n = 1) and unexplained anorexia
      (n = 1). RESULTS: The mean length of artificial nutrition was 20 months (SD:
      11.5), although two of the patients still receive nocturnal enteral drip. Six
      patients resumed a normal feeding pattern within 3 months to 2 years after
      behavior modification program was started. CONCLUSION: According to our
      experience, there is a critical period involved with oral feeding during the
      first year of life. If not aware, children in transition for tube to oral feeding
      may display oral-motor, sensory and developmental feeding problems.

PMID- 9644949
TI  - [Characteristics of fats of some foods of the meats group and their relations
      with health].
AB  - The fatty acids and cholesterol contents of ten fresh protein foods were
      determined, 6 meats (pork, rabbit, lamb, turkey, chicken and beef) and 4 fishes
      (tuna, sea bream, hake and sardine); the fat quality by different chemical index
      of the foods (saturated fat/polyunsaturated fat ratio, index of atherogenicity
      and index of thrombogenicity) and the effect of their intakes on the health were
      also determined. The study shows that the fat content was lower in meat pork than
      lamb, rabbit, tuna, sea bream and sardine; and it was similar to chicken beef and
      hake. Pork, chicken and turkey meat had the lowest content of myristic acid.
      Fishes showed lower index of thrombogenicity than the other analyzed food and
      pork, chicken and turkey showed the lowest atherogenicity index.

PMID- 9644950
TI  - [Use of enteral nutrition products in a general hospital].
AB  - The present work aims to study the use of enteral nutrition (EN) products during
      the period between October 1996 and January 1997, in a general hospital with a
      nutrition unit. The EN expenditure ascended to 3,343,475 Pesetas, with the
      supplements representing the greatest cost percentage (39.1%). An indication
      prescription study was carried out by reviewing 120 clinical histories of
      patients who had received EN during that period. The patients originated in
      different departments of the hospital, excluding the ICU, chronic patients,
      pediatrics, and palliative care. Data regarding sex, age, diagnosis, diet used,
      calories/day given, route of administration, and selection criterion for the diet
      were analysed. The average age of the patients was 64.59 years. The most common
      diagnoses were solid tumors (32.5% of the cases), followed by cerebrovascular
      accidents (16.7% of the cases). The most commonly used EN preparation was the
      Pentadrink hypercaloric diet (36.7% of the cases), followed by the standard diet
      (25.8%). The route of administration used most frequently was the oral route in
      63.3% of the cases. The calories/day given varied per diet, with this being 886
      cal for the hypercaloric diet, and 1,839 cal for the standard diet. Among the
      criteria for selecting an EN diet 50% of the patients had abnormal protein
      metabolism and a normal digestive capacity with slight or moderate stress, 12.5%
      were diabetic; and the remainder presented other criteria that influenced the
      choice for a specific type of EN diet. From the analysis of the results it is
      clear that Pentadrink is used as a supplement, and that there are patients with a
      sometimes insufficient caloric supply.

PMID- 9644951
TI  - [Some current questions concerning occupational diseases in Hungary].
AB  - The author reviews the management of the professional diseases in Hungary from
      the beginning till now. It can be stated that the number of the registered
      professional diseases in Hungary has decreasing steadily. He thinks that this
      tendency can be explained not only by the improvement of the labour higienic
      conditions and systematic screening tests with biologic monitoring but also by
      the increase of unemployment and the threatening of the latter of the workers as
      well as the lack of the discipline of the registration. The change of the
      economical structure resulted in the change of the problems concerning the
      professional diseases too. The liquidation of the old large factories and the
      development of many small economic plants represents a big problem of the labour
      hygienic control of the latters and make difficult the prophylactic examinations
      of all employees. This is a factor counteracting the further decrease of number
      of professional diseases. The change of the spectrum of the professional diseases
      is to be expected too. The criteria of the diagnosing, the therapy and the
      prognosis of the professional diseases are described. The most effective method
      of the medical prevention of the professional diseases in the precise fulfillment
      of the prophylactic medical examinations.

PMID- 9644952
TI  - [Examination of the sentinel lymph node in malignant melanoma].
AB  - The authors report about a new "lymphatic-mapping" method (by means of patent
      blue staining) by which it is able to detect regional (sentinel) lymph node, into
      which the first metastasis is occurred. Experiences were made known with 15
      patients. The by "lymphatic mapping" detected and removed sentinel lymph node has
      an, important role not only in determination of staging, but also in indication
      of prophylactic block-dissection, too.

PMID- 9644953
TI  - ["Open abdomen" in the treatment of necrosis in acute pancreatitis].
AB  - Eleven cases of acute necrotic pancreatitis had been treated by "open abdomen" at
      the author's departments. Nine patients survived, but 2 patients had been lost in
      MOF. Indication, technics and complications are discussed. The author's opinion
      is, that--on the basis of a suitable indication--"open abdomen" is a good method
      in the treatment of the necrosis in acute pancreatitis.

PMID- 9644954
TI  - [Oral rehydration therapy in the management of diarrhea].
AB  - Importance of oral rehydration solution in the treatment of diarrhoeal diseases
      in well-known. It can be applied in all types of diarrhoea, practically, without
      any side effects, complications, such hypernatraemia is avoidable. It has proved
      to be effective for the dehydration, caused by diarrhoea, and for the diarrhoea,
      too. The authors review the position of oralis rehydration liquid in the therapy
      of diarrhoea, the pathophysiology and epidemiology of diarrhoeal diseases. The
      therapeutic practices, suitable composition of oral rehydration solution, cost
      benefit considerations, further possible indications of solution are discussed as
      well. The authors give background information about the modification of the
      composition of oral rehydration solution, recommended by the World Health
      Organization, and call the attention to the importance of the alteration of
      health officer's view about the oral rehydration therapy.

PMID- 9644955
TI  - [Angina pectoris induced by pacemaker syndrome].
AB  - Pacemaker syndrome is caused primarily by the lack of atrial kick and by
      neurocardiogenic reflex mechanisms due to simultaneous atrial and ventricular
      contractions. The most common clinical symptoms are dyspnoe, hypotension,
      dizziness and syncopal attacks. A case report of a patient with pacemaker
      syndrome is presented, in which the main clinical manifestation was a recurrent
      chest pain. A VVI demand pacemaker was implanted because of sick sinus syndrome
      ten years ago and shortly afterwards anginal attacks of rest developed. Coronary
      angiography revealed a non-significant (25%) narrowing of the right coronary
      artery (RCA). Casual and long-term ambulatory blood pressure (ABPM) measurements
      elucidated that the patient occasionally has extremely low diastolic blood
      pressure. This later phenomenon was confirmed and refined by a "beat-to-beat"
      blood pressure measuring technique. The elimination of the pronounced "beat-to
      beat" variability of arterial blood pressure and transient coronary hypoperfusion
      due to implantation of an AV sequential bifocal pacemaker resulted in a full
      disappearance of angina pectoris.

PMID- 9644956
TI  - [Geza Farkas (1872-19340), professor of physiology].

PMID- 9644957
TI  - [History of the stethoscope (Rene Theophile Hyacinthe Laennec)].

PMID- 9644958
TI  - [National Registry of Automatic Implantable Defibrillators in 1996].
AB  - The results of the Spanish Registry of Automatic Defibrillators implanted between
      February 1996 and January 1997 are reported. A questionnaire per patient was
      completed by every implanting physician, in every center. The questionnaire was
      designed by the Section of Electrophysiology and Arrhythmias of the Spanish
      Society of Cardiology. The data from 306 automatic defibrillators implanted were
      reported. The percentage of defibrillators per inhabitant in Spain is close to 1
      per 100,000. Eighty-five percent were first implants, while a 13% were
      replacements. Most of the electrodes used were endocardial. Chronic ischemic
      heart disease was found in 54% of the patients. Forty-six percent of the patients
      had syncopal ventricular tachycardia, 31% ventricular fibrillation and 23%
      sustained monomorphic ventricular tachycardia. The generator pocket was pectoral
      in 87% of the patients and abdominal in 13%. The implant of the defibrillator was
      associated with other cardiac surgery in only 3% of the patients.

PMID- 9644959
TI  - ["The athlete's heart": most common electrocardiographic findings].
AB  - The morphological and functional cardiac adaptations induced by physical training
      may be reflected in several athlete's electrocardiographic variants. Rhythm and
      heart rate disturbances are the most common findings, and sinus bradycardia is
      the most frequent adaptation. Non-specific intraventricular conduction delay and
      incomplete right bundle branch block are also frequent, but other bundle branch
      and fascicular blocks are extremely rare. While the atrioventricular conduction
      may be prolonged, the occurrence of first degree and type I second degree
      atrioventricular blocks depends on the individual's susceptibility. Advanced
      second and third degree atrioventricular blocks are exceptional, and when
      present, the possibility of underlying heart disease must be excluded. High QRS
      voltage is more frequent in male athletes, but its correlation with left
      ventricular hypertrophy is low. The ST segment elevation in the so called "early
      repolarization" pattern is typical of the athlete's electrocardiogram. Vagotonic
      or high T wave voltages and U waves are also frequent when sinus bradycardia is
      present. Tachyarrhythmias and increased automatism arrhythmias are rare and
      usually benign. The increased vagal tone is responsible for the suppression of
      the physiological and ectopic pacemakers. While Wolff-Parkinson-White syndrome
      per se does not exclude an athlete from sports activity, the risk of a sudden
      death makes it mandatory to perform an exhaustive cardiac evaluation. We may
      conclude that no sport can be considered arrhythmogenic or as a predisposing
      factor for malignant ventricular arrhythmias.

PMID- 9644960
TI  - [Sympathetic reinnervation of the transplanted heart. Study using iodine-123
      labeled meta-iodobenzylguanidine].
AB  - INTRODUCTION AND OBJECTIVES: Metaiodobenzylguanidine (MIBG) is an analogue of
      norepinephrine and its cardiac uptake shows sympathetic innervation. During the
      heart transplantation the allograft becomes completely denervated. The present
      study was conducted to assess the evolution of sympathetic re-innervation after
      transplantation, and to related re-innervation with functional status. PATIENTS
      AND METHODS: We studied 31 patients from 6 months to 12 years after
      transplantation by 123I-MIBG studies to evaluate re-innervation and by
      rest/exercise radionuclide ventriculography to evaluate cardiac function.
      Myocardial MIBG uptake was quantified by calculating a heart-to-mediastinum ratio
      (HMR). An HMR > 1.8 was considered normal, moderate between 1.8 and 1.6, mild
      between 1.6 and 1.3, and absent < 1.3. RESULTS: HMR correlated with time after
      transplantation (r = 0.607; p < 0.001). HMR of patients studied after 2 years of
      transplantation was significantly higher (1.62 +/- 0.2 vs 1.34 +/- 0.2; p <
      0.05). MIBG uptake was in the anterior region in 3 patients, in the antero
      lateral region in 25, and in the antero-lateral and septal regions in 3. From a
      functional point of view, peak filling rate at exercise was higher in patients
      studied 2 years after the transplantation (2.7 +/- 0.8 edv/s vs 2.16 +/- 0.5
      edv/s; p = 0.02). These patients also showed a higher increase of heart rate with
      exercise (p < 0.005 vs p < 0.01). CONCLUSIONS: Sympathetic re-innervation
      increase with time after heart transplantation, and is more frequently seen 2
      years after transplantation. Sympathetic re-innervation first appears in the
      anterior or the antero-lateral regions. A complete re-innervation of the
      transplanted heart does not occur 12 years after transplantation.

PMID- 9644961
TI  - [Electromagnetic interference between automatic defibrillators and digital and
      analog cellular telephones].
AB  - BACKGROUND AND OBJECTIVES: Functional pacemaker interference by mobile telephones
      has been described with analogical systems and with possible greater influence,
      digital systems, including inhibition and inadequate pacing. The influence of
      both system has not been extensively studied in patients with implantable
      cardioverter defibrillators (ICD). PATIENTS AND METHODS: We studied the influence
      of mobile phones, both digital and analogic network, on the performance of
      several models of defibrillators, in a standardised test set up designed to
      provide high sensitivity. The purpose of our study was to establish whether there
      are any influences on ICD functions, both in in vivo and in in vitro models.
      Several mobile phones, with different transmission powers, were moved towards the
      defibrillator and the electrode, under continuous documentation of defibrillator
      sensing and interrogation afterwards. The experimental model was performed with
      the aid of an arrhythmia simulator (Intersim) and demo-defibrillators. The tests
      were repeated both in and out of a solution of saline water with an impedance
      within normal human limits. RESULTS: Partial loss of telemetry was found in 14
      patients, 8 with analogical phones and 6 with digital phones. Fourteen patients
      showed alterations only on the surface electrocardiogram channel and five on the
      intracavitary channel. The same results were reproduced in the in vitro model.
      However, the in vitro test allowed us to simulate multiple ventricular
      arrhythmias, and demonstrate the normal sensing and functioning of the
      defibrillator during a "spontaneous" arrhythmia. After testing, we demonstrate
      that no real oversensing/undersensing was documented in any device. There was no
      evidence of ICD reprogramming or pacing inhibition. In particular, no inadequate
      therapies were delivered. CONCLUSIONS: a) in our series, we have not demonstrated
      clinically significant electromagnetic interferences with mobile phones of
      digital or analogical networks: b) the in vitro model allowed us to conclude that
      even if a spontaneous arrhythmia appears, the function of the defibrillator is
      not altered; c) the use of mobile phones seems to be safe for defibrillator
      patients, and d) however, some basic rules, such as to maintain the phone at
      least 15 cm away from the defibrillator, are advised.

PMID- 9644962
TI  - [Long-term follow up of patients with nodal reentry tachycardia who had undergone
      radiofrequency ablation].
AB  - INTRODUCTION: The aim of this study was to assess the long term results (minimum
      of 3 years) of radiofrequency catheter ablation in patients with common (slow
      fast) atrioventricular nodal reentrant tachycardia. PATIENTS AND METHODS: Sixty
      consecutive patients (mean age 56 +/- 16 years, range 14 to 83, 16 men and 44
      women) underwent slow pathway (n = 51, Group A) or fast pathway (n = 9, Group B)
      radiofrequency catheter ablation between January 1992 and March 1994. All
      patients were followed at 1, 3, 6 and 12 months after ablation with serial
      examinations and electrocardiograms and the last follow-up was made on April
      1997. RESULTS: During a mean follow-up period of 48 +/- 7 months (range 38 to 63)
      all evaluated patients remained asymptomatic. Eight recurrences were observed at
      a mean of 1 +/- 2 months (range, 0.5 to 7) after a successful ablation procedure.
      A second procedure was effective in eliminating the dual atrioventricular nodal
      pathway in each of them. In Group A patients, the pre-ablation PR interval, at 12
      months after ablation and at last follow-up were 122 +/- 11, 124 +/- 13 and 124
      +/- 15 ms, respectively. In Group B patients, the pre-ablation PR interval, at 12
      months after ablation and at last follow-up were 130 +/- 24, 200 +/- 12, 200 +/-
      24 ms, respectively. No significant atrioventricular conduction disturbances in
      any patient were observed. One patient developed a new onset left bundle branch
      block and 4 patients died of noncardiac causes. CONCLUSIONS: In patients with
      atrioventricular nodal reentrant tachycardia, radiofrequency catheter ablation is
      a safe and effective therapy, with substantial good results that persist during
      long term follow-up, with a low recurrence rate and without complications during
      short and long term outcome.

PMID- 9644963
TI  - [Quantification of myocardial ischemia in regions dependent on occluded coronary
      arteries in patients without previous infarction].
AB  - INTRODUCTION AND OBJECTIVES: The aim of this study is to assess myocardial
      ischemia in regions with no infarction dependent occluded coronary arteries.
      PATIENTS AND METHODS: 149 patients with proved coronary artery disease and
      without previous myocardial infarction were studied by 99mTc-MIBI SPECT (long
      protocol) and coronary angiography. The extent of the uptake reversibility was
      quantified in 3 regions (antero-septal, inferior and lateral) of the polar maps,
      assessing the percentage of each region that had a > 10% difference resulting
      from the rest uptake minus the stress uptake. The regions dependent on one
      occluded artery were compared to those dependent on non-occluded arteries. In the
      regions dependent on one occluded artery a comparison was also made between those
      which had a good collateral circulation and those which did not. RESULTS: Fifty
      four out of 149 patients (36%) had at least one occluded coronary artery (20
      anterior descending, 22 right and 27 circumflex coronary arteries). In the visual
      analysis, reversible defects were observed in all patients with occlusion of the
      anterior descending and the right coronary artery, but only in half of the
      occlusions of the circumflex coronary artery. The extent of this reversibility
      was significantly higher in the regions dependent on occluded arteries and was
      highly variable, though lower when good collateral circulation was present.
      CONCLUSIONS: Reversible defects were always observed in the occlusions of the
      left anterior descending and right coronary arteries, but only in half of those
      of the circumflex artery. The extent of the ischemia was higher in the regions
      dependent on one occluded coronary artery, mainly when there was an absence of
      good collateral circulation.

PMID- 9644964
TI  - [Pathology of the heart of noncardiac origin. VIII. Cocaine and the heart].
AB  - The marked increase in cocaine consumption observed in recent decades, has led to
      the identification of previously unknown multiple medical problems.
      Cardiovascular complications related to cocaine abuse include myocardial ischemia
      and infarction, myocarditis, cardiomyopathy, rhythm disturbances and sudden
      death, endocarditis, pneumopericardium and left ventricular hypertrophy. Although
      the mechanisms involved in cocaine-related cardiac diseases are multiple, many
      cardiac complications in these patients are caused in part or totally by an
      increase in adrenergic activity due to the blockade of catecholamine reuptake
      induced by the drug.

PMID- 9644965
TI  - [Left atrial dissection and infective endocarditis].
AB  - A rare case of left atrial dissection as a consequence of infectious endocarditis
      is reported. We present a patient with infectious endocarditis with involvement
      of mitral and aortic valves; in whom the trans-esophageal echocardiography was
      able to visualise the left atrial dissection. This complication has been reported
      after surgical repair of the mitral valve, but never in infectious endocarditis.

PMID- 9644966
TI  - [Electrocardiographic changes in hypoglycemia].
AB  - Several electrocardiographic anomalies have been described in association with
      hypoglycaemia. We report the case of a 70-year-old woman with hypoglycaemic coma
      whose electrocardiogram showed significant conduction anomalies, including
      atrioventricular block and intraventricular conduction disturbances, and
      repolarization abnormalities. These electrocardiographic changes disappeared
      after intravenous glucose administration.

PMID- 9644967
TI  - [Ellis-van Creveld syndrome: an easy early diagnosis?].
AB  - Ellis-Van Creveld syndrome is a rare chondroectodermal dysplasia. Congenital
      heart disease is present in more than one-half of cases. The majority are partial
      atrioventricular septal defects and affect the atrial septum. Although isolated
      cases of the syndrome are uncommon, an early diagnosis is made in most of the
      patients because of their cardinal manifestations. The cases of two gypsy
      brothers with Ellis-Van Creveld syndrome and congenital heart disease (ostium
      primum atrial septal defect and single atrium), diagnosed during adulthood, are
      presented.

PMID- 9644968
TI  - [Coronary spasm and heart arrest caused by ventricular fibrillation].
AB  - We report the cases of three young men, heavy smokers, without previous heart
      disease and who were resuscitated after cardiac arrest due to ventricular
      fibrillation attributed to coronary spasm. All of them complained of atypical
      chest pain and the exercise testing, echocardiogram and coronary angiography were
      normal. The first case was diagnosed by Holter monitoring and by provocative
      testing with intracoronary ergonovine; the second by provocative testing with
      intracoronary acetylcholine and the third by Holter monitoring. The patients were
      treated with a calcium antagonist and/or nitrates and in the follow up they
      remained asymptomatic.

PMID- 9644969
TI  - Prions are copper-binding proteins.

PMID- 9644970
TI  - A rule for termination-codon position within intron-containing genes: when
      nonsense affects RNA abundance.

PMID- 9644971
TI  - Diacylglycerols and phosphatidates: which molecular species are intracellular
      messengers?
AB  - In eukaryotes, many receptor agonists use phospholipase-generated lipids as
      intracellular messengers. Receptor occupation stimulates the production of
      polyunsaturated 1,2-diacylglycerols by phosphatidylinositol-4,5-bisphosphate
      specific phospholipases C and/or of mono-unsaturated and saturated phosphatidates
      by phospholipase-D-catalysed phosphatidylcholine breakdown. The primary
      phospholipase products are rapidly metabolized: polyunsaturated 1,2
      diacylglycerols are converted to polyunsaturated phosphatidates by diacylglycerol
      kinase; mono-unsaturated and saturated phosphatidates are dephosphorylated to
      give mono-unsaturated and saturated 1,2-diacylglycerols by phosphatidate
      phosphohydrolase. The phospholipase-generated polyunsaturated 1,2-diacylglycerols
      and mono-unsaturated and saturated phosphatidates appear to be intracellular
      messengers, whereas their immediate metabolites probably do not have signalling
      functions.

PMID- 9644972
TI  - The PCI domain: a common theme in three multiprotein complexes.

PMID- 9644973
TI  - A novel oxidoreductase family sharing a conserved FAD-binding domain.

PMID- 9644974
TI  - Ribosomal protein structures: insights into the architecture, machinery and
      evolution of the ribosome.
AB  - Models of the bacterial ribosome based on recent structural analyses are
      beginning to provide new insights into the protein synthetic machinery. Central
      to evolving models are the high-resolution structures of individual ribosomal
      proteins, which represent detailed probes of their local RNA and protein
      environments. Ribosomal proteins are extremely ancient molecules; the structures
      therefore also provide a unique window into early protein evolution. Many of the
      proteins contain domains that are present in more recently evolved families of
      RNA- and DNA-binding proteins. Such structural homology can be used to predict
      mechanisms by which proteins interact with RNA in the ribosome.

PMID- 9644975
TI  - Ets transcription factors: nuclear effectors of the Ras-MAP-kinase signaling
      pathway.
AB  - The Ets family of transcription factors includes nuclear phosphoproteins that are
      involved in cell proliferation, differentiation and oncogenic transformation. The
      family is defined by a conserved DNA-binding domain (the ETS-DBD), which forms a
      highly conserved, winged, helix-turn-helix structural motif. As targets of the
      Ras-MAPK signaling pathway, Ets proteins function as critical nuclear integrators
      of ubiquitous signaling cascades. To direct signals to specific target genes, Ets
      proteins interact with (other) transcription factors that promote the binding of
      Ets proteins to composite Ras-responsive elements.

PMID- 9644976
TI  - Lead poisoning, haem synthesis and 5-aminolaevulinic acid dehydratase.
AB  - In mammals and yeast, 5-aminolaevulinic acid dehydratase is a zinc-dependent
      enzyme that catalyses the synthesis of porphobilinogen-the pyrrole building block
      that is incorporated into all modified tetrapyrroles, including haem, chlorophyll
      and vitamin B12. The X-ray structure of this enzyme reveals how substitution of
      the catalytically important zinc ion by lead inactivates the enzyme and causes a
      form of pseudo-porphyria.

PMID- 9644977
TI  - The J-domain family and the recruitment of chaperone power.
AB  - The defining feature of the Hsp40 chaperone family is a approximately 70-amino
      acid-residue signature, termed the J domain, that is necessary for orchestrating
      interactions with its Hsp70 chaperone partner(s). J-domain proteins play
      important regulatory roles as co-chaperones, recruiting Hsp70 partners and
      accelerating the ATP-hydrolysis step of the chaperone cycle. Certain proteins
      could have acquired a J domain in order to present a specific substrate(s) to an
      Hsp70 partner and thus capitalize upon chaperone activities when carrying out
      cellular functions. J-domain proteins participate in complex biological
      processes, such as cell-cycle control by DNA tumor viruses, regulation of protein
      kinases and exocytosis.

PMID- 9644978
TI  - [Experience in the use of doxazosin in patients with benign hyperplasia of the
      prostate].
AB  - Selective alpha-1-adrenoblockers are thought promising in current conservative
      treatment of benign prostatic hyperplasia (BPH). The trial of doxazosin (cardura)
      -a selective alpha-blocker--included 78 BPH patients with obstructive urination.
      All the patients received a single daily dose of doxazosin 4-8 mg (mean 5.7 mg).
      60 patients on placebo served as control. The comparison of the effects observed
      in the study vs control group has demonstrated that doxazosin has a favourable
      effect on BPH: it improved quality of life, relieved obstructive symptoms,
      reduced amount of residual urine. There is objective urodynamic evidence on
      decreased infravesical obstruction.

PMID- 9644979
TI  - [Combined use of 5 alpha-reductase inhibitors and alpha-l adrenergic receptor
      blockers in patients with benign prostatic hyperplasia].
AB  - 88 patients with benign prostatic hyperplasia (BPH) were given the inhibitor of 5
      alpha-reductase proscar (finasteride, Merck and Co. Inc., USA) for 12-14 months
      and uroselective blocker of alpha-adrenoreceptors alfuzosin (dalfas, Synthelabo
      Group, France) for 4-5 months. The patients were examined before the combined
      treatment and on the treatment month 1, 3, 6 and 12. The proscar plus alfuzosin
      combination produced a response after 2-3-week treatment due to alpha-blocker
      Further, the effect was enhanced by the action of inhibitor of 5 alpha-reductase.
      Combination of alfuzosin with proscar meets three principal requirements demanded
      of BPH chemotherapy: improves urination, inhibits the growth of adenomatous
      tissue, diminishes the size of the enlarged prostate.

PMID- 9644980
TI  - [Diagnosis of the "valve effect" of the middle lobe of prostate in benign
      prostatic hyperplasia and choice of the treatment method].
AB  - As there are still no accurate criteria of assessing middle-lobe prostatic benign
      hyperplasia contribution through the "valve effect" to development of
      infravesical obstruction, the authors propose to introduce "miction" transrectal
      ultrasonic study. This study provides evidence allowing to divide patients with
      middle-lobe prostatic benign hyperplasia into three groups by the degree of the
      "valve effect". This enables differential approach to choice of the scope of the
      operative intervention.

PMID- 9644981
TI  - [Changes in central hemodynamics in transurethral prostate resection under
      epidural anesthesia].
AB  - Central hemodynamics was studied in 53 patients divided into 3 groups who had
      transurethral resection of the prostate under epidural anesthesia. Patients with
      uneventful course of surgery (group 1) had favourable rearrangement of
      hemodynamic parameters in response to epidural anesthesia. In patients of group 2
      hemodynamics was characterized by addition of negative effects of relative
      hypovolemia. A significant fall of central venous pressure was found in group 3.
      This low venous pressure resulted from the epidural block and contributed much to
      development of hyponatremia in these patients.

PMID- 9644982
TI  - [Long-term results of plastic surgery in hydronephrosis in children].
AB  - 94 children (109 kidneys) with congenital hydronephrosis were treated in 1989
      1997. 67 of them underwent 76 plastic operations: Andersen-Hynes operation on the
      ureteropelvic segment without pelvic resection (n = 53), antevasal pyelopyelo-
      and ureteropyeloanastomosis (n = 18), ureteropyelolysis (n = 5). Excellent, good
      and satisfactory results were obtained in 16.5, 50.6 and 30.4% of cases,
      respectively. The analysis of changes in the renal-cortical index before and
      after plastic operation with reference to hydronephrosis stage and form, type of
      the pelvis evidenced that the best treatment outcomes were achieved in children
      with open hydronephrosis stage II having extrarenal pelvis. Poor outcomes
      occurred in closed hydronephrosis stage III and intrarenal pelvis. Renal
      planimetry, as one of highly informative diagnostic techniques, can be used in
      assessing results obtained in hydronephrosis treatment.

PMID- 9644983
TI  - [Diagnosis and surgical treatment of tumors of the upper urinary tract].
AB  - The author believes that in diagnosis of tumors of the upper urinary tracts more
      information can be obtained at ureteropyeloscopy with retrograde contrasting of
      the urinary tracts and, if necessary, biopsy of abnormal urothelium regions. 19
      patients with pelvic and 4 patients with ureteral tumor were operated on. 2(8.7%)
      patients with tumor in the lower third of the ureter underwent resection with
      Boari operation, classic nephroureterectomy with bladder resection was made in
      15(65.2%) patients, transurethral resection of the wall of the bladder, ostium
      and distal ureter followed by nephroureterectomy was performed in 6(26.1%)
      patients. The latter operative procedure is radical but less traumatic. Five-year
      survival made up 73.9%.

PMID- 9644984
TI  - [Variants of dysfunction of the upper urinary tract in urolithiasis].
AB  - Registration of contractility of the upper urinary tracts (UUT) at multichannel
      impedance ureterography was conducted in 30 patients with concrements in the
      kidneys and ureters before extracorporeal lithotripsy. By defects in urodynamics,
      the patients were divided into 4 groups. The most severe affection of urodynamics
      (low amplitude of the peristalsis, high tonicity of UUT wall) occurred in group
      4. From group 1 to 4 contraction arrhythmia, deformity of contraction complexes,
      retrograde contraction waves were increasing. The index has been calculated for
      estimation of UUT performance in transporting urine.

PMID- 9644985
TI  - [Effects of indirect electrochemical blood oxidation by sodium hypochlorite
      solution on the course on inflammatory process in the kidneys and urinary tract].
AB  - The action of indirect electrochemical blood oxidation with 0.06% solution of
      sodium hypochlorite on kidney and urinary inflammation was studied in experiments
      on 60 non-inbred rat females of 200-250 g body weight. The animals were
      intravesically infected through the catheter with E. coli and Ps. aeruginosa. 3
      days later, after histological verification of acute pyelonephritis, ureteritis,
      cystitis, the animals were injected intraperitoneally 1.0 and 2.0 ml daily of
      sodium hypochlorite solution (control animals) or 0.89% solution of sodium
      chloride. Though no reliable decrease of the bacterial contamination was
      achieved, histologically, there was a marked reduction in morphological signs of
      the inflammation in the kidneys, ureter and urinary bladder on the first day
      after beginning of electrochemical blood oxidation with solution of sodium
      hypochlorite in experimental groups. In experimental group rats morphological
      signs of urinary and renal inflammation for both infections disappeared on days 7
      and 10, respectively. In the control animals morphological signs of the
      inflammation remained after 10 days. Moreover, purulent inflammation was
      registered in the controls infected with Ps. aeruginosa.

PMID- 9644986
TI  - [Effects of antihypertensive therapy on renal function in nephrogenic
      hypertension].
AB  - Radionuclide tracing was performed to study renal function before and after
      hypotensive therapy in 95 patients suffering from nephrogenic hypertension with
      renal failure. It is shown that if hypotensive therapy in such patients brings
      about a blood pressure fall more than 25% of the initial blood pressure, renal
      function declines, the suppression being especially evident in severe renal
      insufficiency.

PMID- 9644987
TI  - [Vascular complications of kidney transplantation].
AB  - 584 kidney transplantations (208 from cadaveric donors, 376 from living relative
      donors) were performed in Medical Faculties of the Istambul University in 1986
      1997. Thrombosis of the renal artery was observed in 2 patients (0.35%). One of
      them had diffused arterial atherosclerosis 4 months after the kidney
      transplantation. In spite of two successful thrombectomies, the patient died 3
      months after the last surgical procedure from cerebral thrombosis. The other
      patient underwent nephrectomy. Hypertension was observed in 63 patients. In 5 of
      them about 50% stenosis of the anastomotic area was detected by doppler duplex
      scan and selective angiogram. Transluminal angioplasty was performed in one
      patient, open surgical correction in one case. Renal vein thrombosis took place
      in 1 (0.2%) patient. In 2 cases (0.35%) 5 and 12 years after the transplantation
      aortic aneurysmal dissection was observed.

PMID- 9644988
TI  - [Comprehensive assessment of the gastroduodenal mucosa before and after
      methylprednisolone pulse-therapy in children with chronic glomerulonephritis].

PMID- 9644989
TI  - [Beta 2-microglobulin as a criterion of dysfunction in the regulation of proximal
      tubular activity in mercuric chloride-induced nephropathy].
AB  - Sublimate nephropathy--modelled pathology of proximal nephron--serves as
      illustration of a pathogenetic role in development of proximal tubular
      dysfunction of enhanced vasoconstrictive potential of angiotensin II in plasma,
      angiotensin II and thromboxane B2 in renal cortex. The multiple regression
      equation has been calculated. The proportional contribution of plasma angiotensin
      II, atrial natriuretic peptide of plasma, cortical angiotensin II, cortical
      thromboxane B2 to regulation of proximal nephron function was the following:
      26.85, 32.72, 10.51 and 10.56%, respectively.

PMID- 9644990
TI  - [Diagnosis and treatment of erectile dysfunction].
AB  - Pathogenesis of erectile dysfunction is well studied now. So another problem
      arises: how to choose individual methods of diagnosis and treatment as well as
      sequence of diagnostic and therapeutic measures. Our method of purposeful
      approach to diagnosis and treatment of erectile dysfunction is based on the
      choice of the patient who decides himself the scope and invasiveness of the
      diagnosis and treatment. The patient makes his choice after he is informed about
      all available diagnostic techniques and treatment methods.

PMID- 9644991
TI  - [Use of lysozyme in the treatment of male infertility].
AB  - The results of the study of the influence of lysozyme on fertile characteristics
      of ejaculate obtained from sterile patients are presented. Improvement of
      functional activity of spermatozoa in vitro due to lysozyme has been determined.
      The method of the treatment of infertile couples by homologous insemination is
      proposed.

PMID- 9644992
TI  - [Foreign body in the bladder].

PMID- 9644993
TI  - [Bacteriotoxic shock as complication of urolithiasis].

PMID- 9644994
TI  - [Overview of lipoprotein and lipids].

PMID- 9644995
TI  - [Apo A-I deficiency].

PMID- 9644996
TI  - [Apo A-I variant].

PMID- 9644997
TI  - [Tangier disease].

PMID- 9644998
TI  - [Apolipoprotein A-II abnormality].

PMID- 9644999
TI  - [Abnormal apolipoprotein B].

PMID- 9645000
TI  - [Familial hypo beta-lipoproteinemia].

PMID- 9645001
TI  - [Apolipoprotein B-100 variants].

PMID- 9645002
TI  - [Normotriglyceridemic abetalipoproteinemia].

PMID- 9645003
TI  - [Hypo beta-lipoproteinemia with selective deletion of apo B-48].

PMID- 9645004
TI  - [Familial defective apolipoprotein B-100].

PMID- 9645005
TI  - [Abnormalities of apolipoprotein E (type III hyperlipoproteinemia)].

PMID- 9645006
TI  - [Apolipoprotein C-II deficiency].

PMID- 9645007
TI  - [Congenital hypoalphalipoproteinemia].

PMID- 9645008
TI  - [Hyperalphalipoproteinemia].

PMID- 9645009
TI  - [Primary type V hyperlipidemia].

PMID- 9645011
TI  - [Primary hypertriglyceridemia].

PMID- 9645010
TI  - [Familial hypercholesterolemia].

PMID- 9645012
TI  - [Familial combined hyperlipidemia].

PMID- 9645013
TI  - [Abetalipoproteinemia].

PMID- 9645014
TI  - [Familial lipoprotein lipase deficiency].

PMID- 9645015
TI  - [Lipoprotein lipase inhibitory factor].

PMID- 9645016
TI  - [Hepatic triglyceride lipase deficiency, hepatic lipase deficiency].

PMID- 9645017
TI  - [High Lp (a) concentrations].

PMID- 9645018
TI  - [Lecithin-cholesterol acyltransferase deficiency and fish eye disease].

PMID- 9645019
TI  - [Polygenic hypercholesterolemia].

PMID- 9645020
TI  - [Sitosterolemia].

PMID- 9645021
TI  - [Cerebrotendinous xanthomatosis (CTX)].

PMID- 9645022
TI  - [Membranous lipodystrophy].

PMID- 9645023
TI  - [Introduction to porphyrin and heme].

PMID- 9645024
TI  - [Acute intermittent porphyria (AIP)].

PMID- 9645025
TI  - [ALAD deficiency porphyria (ADP)].

PMID- 9645026
TI  - [Variegate porphyria (VP)].

PMID- 9645027
TI  - [Hereditary coproporphyria (HCP)].

PMID- 9645028
TI  - [Porphyria cutanea tarda].

PMID- 9645029
TI  - [Hepatoerythropoietic porphyria].

PMID- 9645030
TI  - [Congenital erythropoietic porphyria].

PMID- 9645031
TI  - [Erythropoietic protoporphyria].

PMID- 9645032
TI  - [Sideroblastic anemia].

PMID- 9645033
TI  - [Inborn errors of trace metals].

PMID- 9645034
TI  - [Wilson disease].

PMID- 9645035
TI  - [Menkes disease].

PMID- 9645036
TI  - [Ceruloplasmin deficiency or aceruloplasminemia].

PMID- 9645037
TI  - [Hemochromatosis].

PMID- 9645038
TI  - [Atransferrinemia].

PMID- 9645039
TI  - [Molybdenum cofactor deficiency].

PMID- 9645040
TI  - [Isolated sulfite oxidase deficiency].

PMID- 9645041
TI  - [Introduction to vitamin].

PMID- 9645042
TI  - [Congenital folate malabsorption].

PMID- 9645043
TI  - [Glutamate-formiminotransferase deficiency].

PMID- 9645044
TI  - [Methylenetetrahydrofolate reductase deficiency].

PMID- 9645045
TI  - [Transcobalamin II deficiency].

PMID- 9645046
TI  - [Inherited disorders of cobalamin metabolism].

PMID- 9645047
TI  - [Holocarboxylase synthetase deficiency (early-onset multiple carboxylase
      deficiency)].

PMID- 9645048
TI  - [Biotinidase deficiency (late-onset multiple carboxylase deficiency)].

PMID- 9645049
TI  - [Vitamin B1 dependency].

PMID- 9645050
TI  - [Vitamin B6 dependency syndrome (vitamin B6 dependent seizures, convulsions)].

PMID- 9645051
TI  - [Vitamin D dependency (type I, type II)].

PMID- 9645052
TI  - [Vitamin E deficiency (alpha-tocopherol transfer protein deficiency)].

PMID- 9645053
TI  - [Bilirubin and bile acid: introduction].

PMID- 9645054
TI  - [Neonatal jaundice, hereditary hemolytic anemia].

PMID- 9645055
TI  - [Crigler-Najjar syndrome].

PMID- 9645056
TI  - [Gilbert's syndrome].

PMID- 9645057
TI  - [Dubin-Johnson syndrome].

PMID- 9645058
TI  - [Rotor syndrome].

PMID- 9645059
TI  - [Benign recurrent intrahepatic cholestasis (Summerskill disease)].

PMID- 9645060
TI  - [Fasting hyperbilirubinemia].

PMID- 9645061
TI  - [3 beta-hydroxy-delta 5-C27-steroid-oxidoreductase/isomerase deficiency].

PMID- 9645062
TI  - [Delta 4-3-oxosteroid 5 beta-reductase deficiency].

PMID- 9645063
TI  - [27-Hydroxylase deficiency (cerebrotendinous xanthomatosis)].

PMID- 9645064
TI  - [Peroxisomal disorders].

PMID- 9645065
TI  - [Introduction to peroxisomal disorders].

PMID- 9645066
TI  - [Zellweger syndrome].

PMID- 9645067
TI  - [Neonatal adrenoleukodystrophy].

PMID- 9645068
TI  - [Infantile Refsum disease].

PMID- 9645069
TI  - [Rhizomelic chondrodysplasia punctata (RCDP)].

PMID- 9645070
TI  - [Dihydroxyacetonephosphate acyltransferase (DHAP-AT) deficiency and alkyl-DHAP
      synthase deficiency].

PMID- 9645071
TI  - [X-linked adrenoleukodystrophy (ALD)].

PMID- 9645072
TI  - [Peroxisomal acyl-CoA oxidase deficiency].

PMID- 9645073
TI  - [Bifunctional enzyme deficiency].

PMID- 9645074
TI  - [Peroxisomal 3-ketoacyl-CoA thiolase deficiency].

PMID- 9645075
TI  - [Acatalasemia, Takahara disease].

PMID- 9645076
TI  - [Refsum disease].

PMID- 9645077
TI  - [Primary hyperoxaluria type 1 (PH1)].

PMID- 9645078
TI  - [Other peroxisomal diseases].

PMID- 9645079
TI  - [Lysosomal diseases: an overview].

PMID- 9645080
TI  - [Glycogen storage disease type II].

PMID- 9645081
TI  - [Lysosomal glycogen storage disease without acid maltase deficiency (Danon's
      disease)].

PMID- 9645082
TI  - [Gaucher disease].

PMID- 9645083
TI  - [Niemann-Pick disease [type A and B] (acid sphingomyelinase deficiencies)].

PMID- 9645084
TI  - [Fabry disease (alpha-galactosidase deficiency)].

PMID- 9645085
TI  - [Schindler disease/Kanzaki disease [alpha-N-acetylgalactosaminidase deficiency]].

PMID- 9645086
TI  - [Krabbe disease (globoid cell leukodystrophy)].

PMID- 9645087
TI  - [Metachromatic leukodystrophy].

PMID- 9645088
TI  - [Multiple sulfatase deficiency].

PMID- 9645089
TI  - [Farber disease [Farber lipogranulomatosis], acid ceramidase deficiency].

PMID- 9645090
TI  - [Tay-Sachs disease (beta-hexosaminidase alpha-chain deficiency)].

PMID- 9645091
TI  - [Sandhoff disease (beta-hexosaminidase alpha-chain deficiency)].

PMID- 9645092
TI  - [GM2 ganglioside activator protein deficiency].

PMID- 9645093
TI  - [beta-Galactosidosis (acid beta-galactosidase deficiency: GM1 gangliosidosis,
      Morquio B disease)].

PMID- 9645094
TI  - [Galactosialidosis].

PMID- 9645095
TI  - [GM2 activator protein deficiency (AB variant form of GM2 gangliosidosis)].

PMID- 9645096
TI  - [Prosaposin deficiency].

PMID- 9645097
TI  - [Saposin B deficiency].

PMID- 9645098
TI  - [Saposin C deficiency].

PMID- 9645099
TI  - [Batten disease].

PMID- 9645100
TI  - [Acid lipase deficiency (Wolman disease and cholesteryl ester storage disease:
      CESD)].

PMID- 9645101
TI  - [Mucopolysaccharidosis type I (Hurler syndrome, Scheie syndrome)].

PMID- 9645102
TI  - [Mucopolysaccharidosis type II (Hunter syndrome)].

PMID- 9645103
TI  - [Mucopolysaccharidosis type III (Sanfilippo syndrome)].

PMID- 9645104
TI  - [Mucopolysaccharidosis type IV (Morquio syndrome, beta-galactosidase
      deficiency)].

PMID- 9645105
TI  - [Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome)].

PMID- 9645106
TI  - [Mucopolysaccharidosis type VII (Sly disease)].

PMID- 9645107
TI  - [Congenital hyaluronidase deficiency].

PMID- 9645108
TI  - [Alpha-mannosidosis].

PMID- 9645109
TI  - [Beta-mannosidosis].

PMID- 9645110
TI  - [Fucosidosis].

PMID- 9645111
TI  - [Sialidosis].

PMID- 9645112
TI  - [Aspartylglucosaminuria].

PMID- 9645113
TI  - [Disorders of phosphorylation system of lysosomal enzymes [mucolipidosis II,
      III]].

PMID- 9645114
TI  - [Carbohydrate-deficient glycoprotein (CDG) syndrome (Jaeken syndrome)].

PMID- 9645115
TI  - [Mitochondria: an overview].

PMID- 9645116
TI  - [Electron transfer complex I deficiency].

PMID- 9645117
TI  - [Electron transfer complex II deficiency].

PMID- 9645118
TI  - [Electron transfer complex III deficiency].

PMID- 9645119
TI  - [Electron transfer complex IV (cytochrome c oxidase) deficiency].

PMID- 9645120
TI  - [Mitochondrial DNA depletion].

PMID- 9645121
TI  - [Introduction to connective tissue].

PMID- 9645122
TI  - [Osteogenesis imperfecta].

PMID- 9645123
TI  - [Ehlers-Danlos syndrome].

PMID- 9645124
TI  - [Chondrodysplasia].

PMID- 9645125
TI  - [Alport syndrome].

PMID- 9645126
TI  - [Epidermolysis bullosa hereditaria].

PMID- 9645127
TI  - [Marfan syndrome].

PMID- 9645128
TI  - [Marfan-related conditions].

PMID- 9645129
TI  - [Pseudoxanthoma elasticum].

PMID- 9645130
TI  - [Membrane transport system].

PMID- 9645131
TI  - [Selective congenital glucose, galactose malabsorption in the small intestine].

PMID- 9645132
TI  - [Familial renal glycosuria].

PMID- 9645133
TI  - [Cystinuria].

PMID- 9645134
TI  - [Lysinuric protein intolerance and other cationic aminoacidurias].

PMID- 9645135
TI  - [Hartnup disease].

PMID- 9645136
TI  - [Familial iminoglycinuria].

PMID- 9645137
TI  - [Histidinuria due to a renal tubular defect].

PMID- 9645138
TI  - [Blue diaper syndrome].

PMID- 9645140
TI  - [Renal tubular acidosis].

PMID- 9645139
TI  - [Methionine malabsorption syndrome].

PMID- 9645141
TI  - [Fanconi syndrome].

PMID- 9645142
TI  - [Oculocerebrorenal syndrome of Lowe].

PMID- 9645143
TI  - [Hypophosphatemic vitamin D resistant rickets].

PMID- 9645144
TI  - [Hereditary renal hypouricemia].

PMID- 9645145
TI  - [Lysosomal transport disorders: cystinosis and sialic acid storage disorders].

PMID- 9645146
TI  - [Cystic fibrosis].

PMID- 9645147
TI  - [Alstrom syndrome].

PMID- 9645148
TI  - [Ataxia-telangiectasia].

PMID- 9645149
TI  - [Carbonic anhydrase II deficiency].

PMID- 9645150
TI  - [Lipodystrophy].

PMID- 9645151
TI  - [Norrie disease].

PMID- 9645152
TI  - [Alpha 1-antitrypsin deficiency].

PMID- 9645153
TI  - [Hereditary amyloidosis].

PMID- 9645154
TI  - [Inborn errors of catecholamine metabolism].

PMID- 9645155
TI  - [Primary hypomagnesemia].

PMID- 9645156
TI  - [Cholinesterase deficiency].

PMID- 9645157
TI  - [Dipeptidase deficiency].

PMID- 9645158
TI  - [Alloalbuminemia and analbuminemia].

PMID- 9645159
TI  - [Congenital enterokinase deficiency].

PMID- 9645160
TI  - [Congenital chloride diarrhea].

PMID- 9645161
TI  - [Congenital trypsinogen deficiency].

PMID- 9645162
TI  - [Congenital lipase deficiency].

PMID- 9645163
TI  - [Hypophosphatasia].

PMID- 9645164
TI  - [Trimethylaminuria].

PMID- 9645165
TI  - [Anhaptoglobinemia and hypohaptoglobinemia].

PMID- 9645166
TI  - [Albinism].

PMID- 9645168
TI  - Prenatal ultrasonography in rural hospitals.

PMID- 9645167
TI  - Computed tomography, magnetic resonance imaging and positron emission tomography
      in non-Hodgkin's lymphoma.
AB  - Certain aspects of the use of CT, MR imaging and PET were evaluated in patients
      with non-Hodgkin's lymphoma (NHL) with the aim of determining whether these
      methods may provide practical guidance for improving the management of these
      patients. Subjective evaluation of the tumor pattern on CT images, and
      quantification of tracer uptake using 11C methionine (11C Met) and [18F]
      fluorodeoxyglucose (18FDG) PET in patients with NHL, were performed to determine
      their relations to malignancy grade. An inhomogeneous tumor pattern (I) was found
      on CT in 75% of high-grade tumors, whereas 68% of low-grade tumors were
      homogeneous (H). Sixteen (94%) of the 17 tumors with a severely inhomogeneous
      pattern (I) were high-grade NHL, while 22 (72%) of the 29 homogeneous tumors (H)
      were low-grade. All tumors were clearly visualized with both 11C Met and 18FDG
      PET. The uptake values for 18FDG were significantly-higher in high- than in low
      grade tumors, while no significant differences between the prognostic groups were
      found for 11C Met. A subjective evaluation of the tumor pattern on CT and on MR
      images was performed. An inhomogeneity index (IH8) was also used in MR images to
      make a quantitative assessment of the degree of inhomogeneity to determine their
      relation to prognosis. Patients with localized NHL, treated with radiotherapy,
      had an excellent prognosis irrespective of the degree of inhomogeneity, while
      patients with generalized disease, treated with chemotherapy, had a poor
      prognosis if the tumors were heterogeneous. Among chemotherapy-treated patients,
      all 9 patients with high IH8 values (> 2.56) on MR images and 9 out of 11
      patients with severe inhomogeneities on CT images died. All patients with gastric
      NHL except for one patient with low-grade NHL of the MALT type displayed high
      18FDG uptake at PET corresponding to the pathological findings at endoscopy
      and/or CT. 18FDG correctly excluded gastric NHL in a patient with benign gastric
      ulcer, but was unable to discriminate between gastric NHL and gastric carcinoma.
      The results suggest that 18FDG PET may demonstrate the extension of NHL in the
      gastric wall more accurately than CT and endoscopy. The prognostic importance of
      the size of a residual mass after completion of chemotherapy, and of tumor
      regression rates during chemotherapy, was evaluated in patients with high-grade
      NHL. Neither a large tumor size before treatment nor a large residual tumor after
      treatment correlated with relapse. It appears, however, as if the response rate
      halfway through the therapy may predict the recurrence rate, although statistical
      significance was not reached.

PMID- 9645169
TI  - Prenatal ultrasonography in rural hospitals.

PMID- 9645170
TI  - Answering the hard questions about thrombolysis.

PMID- 9645171
TI  - Answering the hard questions about thrombosis.

PMID- 9645172
TI  - Answering the hard questions about thrombolysis.

PMID- 9645173
TI  - Unexpected death related to restraint for excited delirium: a retrospective study
      of deaths in police custody and in the community.
AB  - BACKGROUND: Some people in states of excited delirium die while in police
      custody. Emerging evidence suggests that physical restraint in certain positions
      may contribute to such deaths. In this study the authors determined the frequency
      of physical restraint among people in a state of excited delirium who died
      unexpectedly. METHODS: The authors reviewed the records of 21 cases of unexpected
      death in people with excited delirium, which were investigated by the Office of
      the Chief Coroner for Ontario between 1988 and 1995. Eyewitness testimony,
      findings during postmortem examinations, clinical history, toxicological data and
      other official documents describing the events surrounding the deaths were
      analyzed. Specific reference was made to documented eyewitness testimony of
      restraint method, body position and use of capsicum oleoresin (pepper) spray.
      Because cocaine was detected in the blood of some of these people during the
      postmortem examination, the role of cocaine in excited delirium was examined by
      comparing the cocaine levels in these cases with levels in 2 control groups: 19
      people who died from acute cocaine intoxication and 21 people who had used
      cocaine shortly before they died but who had died from other causes. RESULTS: In
      all 21 cases of unexpected death associated with excited delirium, the deaths
      were associated with restraint (for violent agitation and hyperactivity), with
      the person either in a prone position (18 people [86%]) or subjected to pressure
      on the neck (3 [14%]). All of those who died had suddenly lapsed into
      tranquillity shortly after being restrained. The excited delirium was caused by a
      psychiatric disorder in 12 people (57%) and by cocaine-induced psychosis in 8
      (38%). Eighteen people (86%) were in police custody when they died. Four (19%)
      had been sprayed with capsicum oleoresin, and heart disease was found in another
      4 at autopsy. The blood level of cocaine in those whose excited delirium was
      cocaine induced was similar to levels found in recreational cocaine users and
      lower than levels found in people who died from cocaine intoxication.
      INTERPRETATION: Restraint may contribute to the death of people in states of
      excited delirium, and further studies to test this hypothesis are recommended.
      Meanwhile, law enforcement authorities and others should bear in mind the
      potential for the unexpected death of people in states of excited delirium who
      are restrained in the prone position or with a neck hold.

PMID- 9645174
TI  - Death by restraint.

PMID- 9645175
TI  - How do we interpret the results of the Breast Cancer Prevention trial?

PMID- 9645176
TI  - Tamoxifen and breast cancer prevention: what should you tell your patients?

PMID- 9645177
TI  - Unconventional therapies for cancer: 6. 714-X. Task Force on Alternative
      Therapeutic of the Canadian Breast Cancer Research Initiative.

PMID- 9645178
TI  - Preventing disability from work-related low-back pain. New evidence gives new
      hope--if we can just get all the players onside.
AB  - Despite the publication in the mid-1990s of comprehensive practice guidelines for
      the management of acute low-back pain, both in the United States and elsewhere,
      this ubiquitous health problem continues to be the main cause of workers'
      compensation claims in much of the Western world. This paper represents a
      synthesis of the intervention studies published in the last 4 years and is based
      on a new approach to categorizing these studies that emphasizes the stage or
      phase of back pain at the time of intervention and the site or agent of the
      intervention. Current thinking suggests that medical management in the first 3-4
      weeks after the onset of pain should be generally conservative. Several studies
      of rather heterogeneous interventions focusing on return to work and implemented
      in the subacute stage (3-4 to 12 weeks after the onset of pain) have shown
      important reductions in time lost from work (by 30% to 50%). There is substantial
      evidence indicating that employers who promptly offer appropriately modified
      duties can reduce time lost per episode of back pain by at least 30%, with
      frequent spin-off effects on the incidence of new back-pain claims as well.
      Finally, newer studies of guidelines-based approaches to back pain in the
      workplace suggest that a combination of all these approaches, in a coordinated
      workplace-linked care system, can achieve a reduction of 50% in time lost due to
      back pain, at no extra cost and, in some settings, with significant savings.

PMID- 9645179
TI  - The days that will still be mine.

PMID- 9645180
TI  - Just when you thought it was safe to eat a burger....

PMID- 9645181
TI  - Does Canada face a crisis? US considers ending plasma exports.
AB  - A shortage of intravenous immunoglobulin has caused the US to question its
      exports of plasma. Since Canada relies on these exports to provide 60% of its
      plasma, closing the borders could have serious consequences.

PMID- 9645182
TI  - "I won't do surgery if you don't try to do my job," head of new blood agency
      tells MDs. Interview by Anne Mullens.
AB  - Ken Fyke is known as a tough administrator, and he is going to need all of his
      administrative tricks as first chair of Canadian Blood Services, the new national
      organization that is taking over responsibility for the nation's blood supply
      from the Red Cross come September. Fyke says he hopes to work closely with
      physicians, but they will have to realize where their responsibilities end and
      his begin.

PMID- 9645183
TI  - MDs who need psychiatric help afraid to seek it, conference told.

PMID- 9645184
TI  - [Individually dosed levothyroxine with 150 micrograms iodide versus 100
      micrograms levothyroxine combined with 100 micrograms iodide. A randomized double
      blind trial].
AB  - BASIC PROBLEM AND OBJECTIVE: Intrathyroid deficiency and the influence of thyroid
      stimulating hormone (TSH) are the main pathogenetic factors in the development of
      endemic euthyroid goitre. Goitre reduction is achieved with either administration
      of levothyroxine, which diminishes hypophyseal TSG production, or of iodide. Aim
      of this study was to compare the efficacy of treatment with a dose-fixed
      combination of levothyroxine plus iodide with that of an individualized dosage of
      levothyroxine plus iodide. PATIENTS AND METHODS: After randomization 49 patients
      with euthyroid goitre (24 women, 25 men, aged 20-43 years) were treated for 12
      weeks in a double-blind trial. Patients in group A received levothyroxine in a
      weight-adapted dosage (75,100 or 150 micrograms) plus 150 micrograms iodide,
      while those in group B were given a fixed dosage of 100 micrograms levothyroxine
      plus 100 micrograms iodide. Basal TSH, thyroid hormones, iodide excretion,
      hyperthyroid score and sonographic volume of the thyroid were determined before
      treatment and after 12 weeks. RESULTS: Basal TSH levels were reduced in both
      groups (P < 0.0001), without significant difference between the two groups
      (median relative change: group A 78.1%, group B 52.8%). Thyroid volume was
      decreased independently of the form of treatment (P < 0.0001) (median relative
      reduction: group A 37.6%, group B 30.9%; difference not significant). Iodide
      excretion rose in both groups, without significant difference (group A 107%,
      group B 49%). There was hardly any change of the hyperthyroid score in both
      groups. There were no side effects. CONCLUSION: Both forms of medication were
      equally efficacious and well tolerated in the treatment of euthyroid goitre.

PMID- 9645185
TI  - [Fatal pulmonary embolism after endoscopic embolization of downhill esophageal
      varix].
AB  - HISTORY AND CLINICAL FINDINGS: A 79-year-old man was admitted with a history of
      recent haematemesis and tarry stools. 4 years before he had undergone a subtotal
      thyroidectomy for hyperthyroidism. INVESTIGATIONS: He was anaemic (haemoglobin
      7.2 g/dl, haematocrit 23%). At the transition between the upper and middle third
      of the oesophagus gastroscopy revealed a bleeding oesophageal varix. TREATMENT
      AND COURSE: The bleeding varix was sclerosed with polidocanol. 3 erythrocyte
      concentrates were administered. Massive bleeding 2 days later was controlled with
      intravaricose injection of cyanoacrylate (Histoacryl). The patient died 6 weeks
      later from progressive cardiovascular failure. Autopsy revealed the cause of
      death as right heart failure with extensive foreign-body pulmonary emboli
      identified as thrombotic material containing polymerized cyanoacrylate found in
      the previously injected oesophageal varix. Also discovered was a retrosternal
      goitre which had compressed the brachiocephalic vein. Cause of the "washing-out"
      of the cyanoacrylate embolus from the varix into the systemic circulation was an
      oesophago-varicose collateral circulation in a cranio-caudal direction; this had
      been formed by the pressure of the retrosternal goitre on the brachiocephalic
      vein. CONCLUSION: Cyanoacrylate injection into a varix above the lower third of
      the oesophagus should only be done under strict indication. A similar risk as
      that described in this case potentially exists in the treatment of acute bleeding
      from a portosystemic varicose circulation.

PMID- 9645186
TI  - [Erroneous intravenous injection of adrenaline].
AB  - HISTORY AND CLINICAL FINDINGS: Since a car accident a 29-year-old man had been
      suffering from chronic pain treated with injections of morphine and tilidine.
      Because of renewed worsening of pain he went to the emergency doctor who by
      mistake intravenously injected 1 mg of undiluted adrenaline. The patients
      immediately collapsed and pulmonary oedema developed. INVESTIGATIONS: On
      admission he was hypotensive (85/45 mmHg) and tachycardic (135/min), respiratory
      rate 36/min. Moist rales were heard throughout the lung. The white cell count was
      elevated and serum potassium low (3.5 mmol/l). but other routine laboratory tests
      were unremarkable. TREATMENT AND COURSE: Furosemide, nitroglycerin and morphine
      were injected at once and his general state improved over the subsequent few
      hours. Chest radiogram on the next day demonstrated marked reduction of the
      pulmonary oedema. CONCLUSION: To prevent similar, potentially lethal, accidents,
      before every i.v. injection two persons should check the name of the drug on the
      label of the vial or bottle, both on drawing up and before injecting the drug.

PMID- 9645187
TI  - [Catheter ablation of atrial flutter. A dependable therapeutic procedure].

PMID- 9645188
TI  - [Help for patients with multiple sclerosis: current diagnostic and treatment
      possibilities in neurogenic disorders of bladder emptying].

PMID- 9645189
TI  - [Fluoride treatment of osteoporosis. What is its current status?].

PMID- 9645190
TI  - Early events in human myelopoiesis.

PMID- 9645191
TI  - Objective malignancy grading: a review emphasizing unbiased stereology applied to
      breast tumors.
AB  - Low reproducibility reduces the clinical value of morphologic grading of
      malignant tumors, and the replacement of subjective classification by objective
      quantification has been suggested. Simple mitosis counting has been employed for
      objective malignancy grading most frequently and has proved its prognostic
      significance in, e.g., sarcomas and carcinomas of the breast and ovary. These and
      other measurements of morphometry are, however, obtained in two dimensions only,
      introducing bias due to ignorance of the fact that biologic structures are three
      dimensional. Stereologic estimators are, to that end, well-suited, because they
      enable the assessment of spatial structure from sections. Studies addressing the
      impact of stereology in tumor pathology are the subject of the current review.
      Details of estimation are provided of stereologic variables of tumor size,
      numbers and densities of cancer cell nuclei and mitoses, mean size and size
      variability of cancer cell nuclei and variables of tissue architecture. Besides a
      description of their practical estimation the influence on variables of sampling
      method, tissue processing and observer variability is assessed, and estimator
      efficiency and measuring equipment is evaluated. Exemplifying the clinical
      importance of objective grading, results are summarized of prognostic studies of
      quantitative histopathology in women with breast cancer. It has been shown that
      many stereologic estimators are applicable to ordinary histologic sections
      processed under routine conditions. If a systematic random scheme of sampling is
      employed then the efficiency of estimation is usually high, and reproducible,
      accurate and representative results are ensured. For objective malignancy grading
      of breast cancer especially the volume-weighted mean nuclear size, vv (nuc),
      seems valuable, and the variable usually provides independent information to that
      of staging parameters. The prognostic value of vv (nuc) seems greatest in lymph
      node positive subsets, whereas the importance in lymph node negative patients
      should be further investigated. The clinical significance of some stereologic
      variables may be restricted due to relatively time consuming measurement
      procedures. However, the unbiased technique may provide precise measures of basic
      parameters like "tumor burden" and tumor growth pattern, and thereby be highly
      useful in experimental oncology. In conclusion, stereology is of great value for
      quantifying tumor elements. For objective malignancy grading especially
      assessment of the three-dimensional mean nuclear size seems useful. Prognostic
      significance of this variable has been demonstrated in, e.g., malignant melanoma
      and carcinomas of the breast, lung, bladder, prostate and uterine cervix. To
      determine the real clinical value of the measurements, further evaluation in a
      routine setting is necessary. In case such prospective studies confirm previous
      findings, the future replacement of subjective grading techniques by
      reproducible, objective variables seems feasible.

PMID- 9645192
TI  - Differences in virus receptor for type I and type II feline infectious
      peritonitis virus.
AB  - Feline infectious peritonitis viruses (FIPVs) are classified into type I and type
      II serogroups. Here, we report that feline aminopeptidase N (APN), a cell-surface
      metalloprotease on the intestinal, lung and kidney epithelial cells, is a
      receptor for type II FIPV but not for type I FIPV. A monoclonal antibody (MAb) R
      G-4, which blocks infection of Felis catus whole fetus (fcwf-4) cells by type II
      FIPV, was obtained by immunizing mice with fcwf-4 cells which are highly
      susceptible to FIPV. This MAb also blocked infection of fcwf-4 cells by type II
      feline enteric coronavirus (FECV), canine coronavirus (CCV), and transmissible
      gastroenteritis virus (TGEV). On the other hand, it did not block infection by
      type I FIPVs. MAb R-G-4 recognized a polypeptide of relative molecular mass 120
      130 kDa in feline intestinal brush-border membrane (BBM) proteins. The
      polypeptide possessed aminopeptidase activity, and the first 15 N-terminal amino
      acid sequence was identical to that of the feline APN. Feline intestinal BBM
      proteins and the polypeptide reacted with MAb R-G-4 (feline APN) inhibited the
      infectivity of type II FIPV, type II FECV, CCV and TGEV to fcwf-4 cells, but did
      not inhibit the infectivity of type I FIPVs.

PMID- 9645193
TI  - Dissociation of ligand-induced internalization of CXCR-4 from its co-receptor
      activity for HIV-1 Env-mediated membrane fusion.
AB  - The C-terminal cytoplasmic tail of chemokine receptors is important for their
      internalization upon ligand binding. We generated several deletion mutants of the
      C-terminal cytoplasmic tail of CXCR-4, a co-receptor for T cell line tropic
      strains of human immunodeficiency virus type 1 (HIV-1), to know whether or not co
      receptor internalization is associated with HIV-1 entry. Our data showed that the
      removal of C-terminal 15 amino acid residues of the cytoplasmic tail from CXCR-4
      completely abolished its internalization, but did not affect the co-receptor
      activity at all. Co-receptor activity was fully retained even when all 45 amino
      acid residues in the C-terminal cytoplasmic tail had been deleted. These data
      indicated that no cytoplasmic tail nor internalization of CXCR-4 is required for
      its co-receptor activity for HIV-1 entry.

PMID- 9645194
TI  - Characterization of the UL16 gene product of herpes simplex virus type 2.
AB  - We have raised rabbit polyclonal antisera against a His-tagged herpes simplex
      virus type 1 (HSV-1) UL16 fusion protein, one of which very specifically reacted
      with 40 kDa and 41 kDa proteins in the lysates of HSV-1 and HSV-2-infected cells,
      respectively. Since its reactivity to the 41 kDa protein was clearly eliminated
      by pre-adsorption with E. coli lysates expressing the UL16 fusion protein, the
      antiserum was used to characterize the UL16 products of HSV-2. The HSV-2 UL16
      protein was produced at the late phase of infection in a manner highly dependent
      on viral DNA synthesis and was distributed in both the nuclei and the cytoplasma
      of infected cells. In immunofluorescence studies, the UL16-specific fluorescence
      in the nuclei was shown to be detected as small discrete granules. On the other
      hand, the cytoplasmic fluorescence was diffusely distributed around the nucleus
      at 8 h postinfection but, at later times of infection, it was mainly detected as
      a mass at a perinuclear region. The analysis on its association with capsids has
      revealed that the UL16 protein copurified with C capsids but not B and A capsids,
      and that the association with C capsids was not tight. Moreover, our experiments
      have shown that a detectable level of the UL16 protein was not associated with
      extracellular virions, and that the partially purified UL16 proteins had a DNA
      binding activity. These observations are consistent with the hypothesis that the
      UL16 protein plays a role in capsid maturation including DNA packaging/cleavage.
      We have also determined the complete nucleotide sequence of the HSV-2 UL16 gene
      and found that a nonstandard initiation codon may be used for its translation.

PMID- 9645195
TI  - Slight difference in primary amino acid sequence of p17 matrix protein of HIV-1
      exerts profound influence on its antigenicity.
AB  - HIV-1 p17 antigen has been studied for its biological significance in vitro as
      well as its immunological roles in vivo. By immunological approach of antibody
      binding to HIV-1 p17 antigens of several subtypes in combination with
      computerized analysis of those tertial structures, it became evident that,
      irrelevant of similarity of linear amino acid sequence of different HIV-1
      subtypes, a few amino acid substitutions close to or distant from specified
      epitope(s) affected their tertial structure resulting in change in ability of its
      binding to selected antibody. ELISA employing two monoclonal antibodies, A144 and
      C415, could detect p17 of subtypes A and B, but not of subtypes C, D, and E.
      Since the epitope site corresponding to A144 has been reported to be important
      for biological activity of p17 of HIV-1, change in tertial structure around this
      epitope may explain some difference in biology of HIV-1, such as infectivity of
      subtypes B and E.

PMID- 9645196
TI  - Direct sequencing of the HA gene of clinical equine H3N8 influenza virus and
      comparison with laboratory derived viruses.
AB  - Equine influenza viruses propagated in the laboratory in alternate hosts such as
      embryonated hens' eggs or mammalian cell culture have been analysed by HA
      sequencing and antigenically and their sequence compared to the original virus
      present in clinical material. In contrast to clinically derived human influenza
      virus which generally grows in MDCK cells without change, the data for equine
      influenza virus were less clear in that variants of equine virus were derived in
      both eggs and cells. The study indicated that the current use of eggs for equine
      influenza virus surveillance and vaccine production is entirely appropriate, but
      that care should be exercised when equine influenza vaccines are produced in eggs
      or on mammalian cell cultures.

PMID- 9645197
TI  - Ceratobium mosaic potyvirus: another virus from orchids.
AB  - A potyvirus, which we call ceratobium mosaic virus, has been detected in about
      one third of more than 100 plants representing c. 33 orchid genera in two
      collections in Australia. It was detected using RT-PCR with redundant primers
      that are Potyviridae-specific and have additional sequences corresponding to
      either the SP6 or T7 bacteriophage promoters at their 5'-termini. Thus the
      nucleotide sequence of the resulting PCR fragments, consisting of about 1.7 kb of
      the 3' portion of the viral genome, could be determined directly. Viral sequences
      obtained from five infected orchids indicate that they contained different
      isolates of a single potyvirus species most closely related to the bean common
      mosaic group of potyviruses, but clearly distinct from all whose virion protein
      genes have been reported to the international gene sequence databases.

PMID- 9645198
TI  - Fowl adenovirus recombinant expressing VP2 of infectious bursal disease virus
      induces protective immunity against bursal disease.
AB  - The right hand end Nde I fragment 3 (90.8-100 map units) of the fowl adenovirus
      serotype 10 (FAV-10) was characterised so as to allow the location of an
      insertion site for recombinant vector construction. Infectious bursal disease
      virus (IBDV) VP2 gene from the Australian classical strain 002/73, under the
      control of the FAV-10 major late promoter/leader sequence (MLP/LS) was inserted
      into a unique Not I site that was generated at 99.5 map units. This recombinant
      virus was produced without deletion of any portion of the FAV-10 genome. When
      administered to specific pathogen free (SPF) chickens intravenously,
      intraperitoneally, subcutaneously or intramuscularly, it was shown that the FAV
      10/VP2 recombinant induced a serum VP2 antibody response and protected chickens
      against challenge with IBDV V877, an intermediate virulent classical strain.
      Birds were not protected when the recombinant was delivered via the conjunctival
      sac.

PMID- 9645199
TI  - Membrane association and RNA binding of recombinant hepatitis A virus protein 2C.
AB  - The direct function of hepatitis A virus (HAV) protein 2C, a putative NTPase, is
      not known, yet genetic evidence obtained from chimeric viruses carrying the 2C
      genomic region of different HAV variants indicates that it plays a pivotal role
      in viral replication. In a first assessment of its potential function(s),
      membrane and RNA binding properties of HAV 2C were studied after expressing the
      protein in various recombinant systems. In contrast to poliovirus 2C, expression
      of HAV 2C was inhibitory to the growth and protein synthesis of bacteria.
      Deletion of the N-terminal amphipathic helix of 2C abrogated this effect and the
      ability of 2C to associate with eukaryotic membranes. Both, purified 2C and the N
      terminally truncated protein were shown to bind RNA in vitro. Our data taken
      together suggest that HAV 2C is a multifunctional protein.

PMID- 9645200
TI  - Cassava vein mosaic virus (CsVMV), type species for a new genus of plant double
      stranded DNA viruses?
AB  - The complete sequence of 8159 nucleotides of the double stranded DNA genome of
      cassava vein mosaic virus (CsVMV) was determined (# U59751) and revealed a
      significant difference in genome organization when compared with a previous
      report (# U20341). When transferred to cassava plants by microbombardment, the
      full length CsVMV clone was infectious, confirming the genome organization here
      described. Sequence comparisons between CsVMV and members of the genera
      Caulimovirus and Badnavirus revealed high homologies between consensus sequences
      of several proteins that are indispensable for virus replication, including a
      potential transactivator factor not reported previously. The presence of a
      sequence complementary to a plant Met tRNA confirms that CsVMV is a plant
      pararetrovirus and is most closely related to members of the genus Caulimovirus
      as previously assessed. However, differences in genome organization, number and
      size of the ORFs, in addition to sequence comparisons with other plant
      pararetroviruses, shows that either the genetic variability of caulimoviruses is
      much greater than previously thought, or that CsVMV is the unique representative
      of a new genus within the Caulimoviridae family. On the basis of this study, it
      is proposed to upgrade the floating genus Caulimovirus to the family level and to
      divide the Caulimoviridae family into at least three genera with CsVMV being the
      type member of a new genus.

PMID- 9645201
TI  - Characterization of Trichomonas vaginalis virus proteins in the pathogenic
      protozoan T. vaginalis.
AB  - The 4.6-kb double-stranded (ds) RNA of Trichomonas vaginalis virus (TVV)-T1 has
      been shown to encode two overlapping genes, cap and pol. In this study, a serum
      for specifically detecting viral cap gene product was raised against a
      recombinant protein, and sera for specifically detecting pol gene product were
      raised against synthetic oligopeptides. A 75-kDa major protein and a 160-kDa
      minor protein were detected by anti-CAP serum in a TVV-T1 sample, indicating that
      the 75-kDa protein is the viral capsid protein. The 160-kDa protein alone was
      also detected by two distinct anti-POL sera, indicating that the pol gene is
      expressed as a CAP-POL fusion protein. These results suggest that the TVV-T1
      genome is arranged into a cap-pol organization in a manner similar to that of
      viruses in family Totiviridae.

PMID- 9645202
TI  - Citrus viroid Ia is a derivative of citrus bent leaf viroid (CVd-Ib) by partial
      sequence duplications in the right terminal region.
AB  - Nucleotide sequences of group I citrus viroids Ia (CVd-Ia) and citrus bent leaf
      viroid (CBLVd, formerly designated CVd-Ib) isolated from citrus plants in Japan,
      the Philippines and China have been determined. Citrus samples in Japan and the
      Philippines contained CVd-Ia, which consists of 328 nucleotides(nt). Although 10
      nt longer than the type CBLVd-225A in Israel they share 94% identity in overall
      nucleotide sequence. The Philippines sample also contained a 329-nt long CVd-Ia
      sequence variant, in which one base insertion and three substitutions were
      observed. A citrus in China contained CBLVd, which consists of 318 nt and shares
      98% identity to CBLVd-225A. CVd-Ia was clearly separated from CBLVd by two 5-nt
      insertions located in upper (5'-AGCUG-3') and the lower (5'-CUUCU-3') strand of
      the right terminal region (which is also designated T2 domain) in rod-like
      secondary structure. Since both of the additional 5-nt sequences are similar to
      the adjacent sequences (5'-AGUUG-3' and 5'-CUUCU-3'), we hypothesize that CVd-Ia
      is a derivative of CBLVd caused by partial sequence duplications and
      substitutions taking place in the right terminal region.

PMID- 9645203
TI  - In vivo interactions among rotavirus nonstructural proteins.
AB  - The rotavirus genome encodes six nonstructural (NS) proteins, five of which
      (NSP1, NSP2, NSP3, NSP5, and NSP6) have been suggested to be involved in a
      variety of events, such as genome replication, regulation of gene expression, and
      gene assortment. These NS proteins have been found to be associated with
      replication complexes that are precursors of the viral core, however, little
      information is available about the intermolecular interactions that may exist
      among them. Using the yeast two-hybrid system, which allows the detection of
      protein-protein interactions in vivo, all possible combinations among the
      rotavirus NS proteins were tested, and several interactions were observed. NSP1
      interacted with the other four proteins tested; NSP3 associated with itself; and
      NSP5 was found to form homodimers and to interact with NSP6. Co
      immunoprecipitation of proteins from rotavirus-infected cells, using hyperimmune
      sera monospecific for the NS proteins, showed the same interactions for NSP1 as
      those observed in yeast. Immunofluorescence co-localization analysis of virus
      infected epithelial cells revealed that the intracellular distribution of
      proteins that were seen to interact in yeast had patterns of distribution that
      would allow such intermolecular interactions to occur. These findings should
      contribute to the understanding of the role these proteins play in different
      aspects of the virus replication cycle.

PMID- 9645204
TI  - Protective efficacy of a dengue 2 DNA vaccine in mice and the effect of CpG
      immuno-stimulatory motifs on antibody responses.
AB  - A recently described DNA vaccine for dengue (DEN) type 2 was shown to elicit high
      levels of neutralizing antibodies in mice. The vaccine candidate consists of the
      PreM and 92% of the envelope genes of DEN 2 New Guinea C strain. We further
      evaluated this DNA vaccine candidate by examining the effect of immuno
      stimulatory CpG DNA motifs on antibody response and by studying the protective
      efficacy of the vaccine. The results showed that CpG motifs present in pUC 19
      significantly improved the antibody response to a suboptimal dose of 3.1
      micrograms of the DEN DNA vaccine. In a lethal mouse intracerebral challenge
      model, the vaccine provided a significant level of protection. Sixty percent of
      the mice immunized with the DEN DNA vaccine plus pUC 19 survived the challenge
      compared to only 10% in the control group that received vector plus pUC. These
      studies illustrate that nucleic acid immunization is a viable approach to
      developing a DEN vaccine and that immuno-stimulatory CpG DNA motifs can be used
      to lower the minimum dose required to produce an antibody response.

PMID- 9645205
TI  - Comparison of the coat protein, movement protein and RNA polymerase gene
      sequences of Australian, Chinese, and American isolates of barely yellow dwarf
      virus transmitted by Rhopalosiphum padi.
AB  - Barely yellow dwarf luteovirus-GPV (BYDV-GPV) is a common problem in Chinese
      wheat crops but is unrecorded elsewhere. A defining characteristic of GPV is its
      capacity to be transmitted efficiently by both Schizaphis graminum and
      Rhopaloshiphum padi. This dual aphid species transmission contrasts with those of
      BYDV-RPV and BYDV-SGV, globally distributed viruses, which are efficiently
      transmitted only by Rhopaloshiphum padi and Schizaphis graminum respectively. The
      viral RNA sequences encoding the coat protein (22K) gene, the movement protein
      (17K) gene, the region surrounding the conserved GDD motif of the polymerase gene
      and the intergenic sequences between these genes were determined for GPV and an
      Australian isolate of BYDV-RPV (RPVa). In all three genes, the sequences of GPV
      and RPVa were more similar to those of an American isolate of BYDV-RPV (RPVu)
      than to any other luteovirus for which there is data available. RPVa and RPVu
      were very similar, especially their coat proteins which had 97% identity at the
      amino acid level. The coat protein of GPV had 76% and 78% amino acid identity
      with RPVa and RPVu respectively. The data suggest that RPVu and RPVa are
      correctly named as strains of the same serotype and that GPV is sufficiently
      different from either RPV strain to be considered a distinct BYDV type. The coat
      protein and movement protein genes of GPV are very dissimilar to SGV. The
      polymerase sequences of RPVu, RPVa and GPV show close affinities with those of
      the sobemo-like luteoviruses and little similarity with those of the carmo-like
      luteoviruses. The sequences of the coat proteins, movement proteins and the
      polymerase segments of BYDV serotypes, other than RPV and GPV, form a cluster
      that is separate from their counterpart sequences from dicot-infecting
      luteoviruses. The RPV and GPV isolates consistently fall within a dicot-infecting
      cluster. This suggests that RPV and GPV evolved from within this group of
      viruses. Since these other viruses all infect dicots it seems likely that their
      common ancestor infected a dicot and that RPV and GPV evolved from a virus that
      switched hosts from a dicot to a monocot.

PMID- 9645206
TI  - Coat protein sequence of Krish-infecting strain of Johnsongrass mosaic potyvirus.
AB  - The morphology of an Australian strain of Johnsongrass mosaic potyvirus (JGMV
      Krish-infecting strain), capable of infecting sorghums carrying the Krish
      potyvirus resistance gene, was investigated and the base sequence of the coat
      protein region determined. Under the electron microscope the virus was
      indistinguishable from the wild type prevalent in Australia, JGMV-Jg. However,
      there were some significant changes in the inferred amino acid sequence in both
      the N-terminus and the core regions of the coat protein. Some of these amino acid
      changes may be responsible for breaking the resistance of sorghums carrying the
      Krish virus resistance gene. In the discussion mention is made of a preliminary
      result with a mutated in vitro transcript which supports this suggestion.

PMID- 9645207
TI  - Molecular and immunologic characterization of group A bovine rotavirus field
      isolates with P8[11] spike protein.
AB  - Bovine rotavirus strain B223 is the North American prototype for group A P8[11]
      serotype/genotype rotaviruses. Rotaviruses with this serotype/genotype are a
      prevalent cause of neonatal calf diarrhea and have also been isolated from
      asymptomatic human infants. On the basis of deduced amino acid sequence of the
      outer capsid viral protein 4 (VP4), strain B223 lacks a cysteine at position 318
      that is conserved among all other rotavirus strains. It has been speculated that
      this may result in the loss of disulfide bond and a change in the structure of
      the VP4 that may affect the infectivity and antigenicity of the virus. This paper
      describes partial sequences of the VP4 gene (nucleotides 613 to 1016 coding for
      amino acid positions 202 to 335) of 16 bovine rotavirus field isolates with
      P8[11] that were obtained from calves in Nebraska and Indiana. All the isolates
      lack a cystein at position 203 and had a conserved valine residue at position
      318, thus indicating that the prototype strain B223 is representative of group A
      rotaviruses with P8[11] serotype/genotype.

PMID- 9645208
TI  - HTLV-1 in mouthwash cells from a TSP/HAM patient and asymptomatic carriers.
AB  - Using in situ hybridization, the presence of T-cell lymphotrophic virus type I
      (HTLV-I) was shown in blood lymphocytes of one tropical spastic paraparesis
      (TSP/HAM) patient and in two asymptomatic carriers. HTLV-I was also detected in
      epithelial cells derived from mouthwash of the TSP/HAM patient. Mouthwash of one
      of the carriers showed an infected lymphocyte while mouthwash of the other
      carrier was negative. The infected epithelial cells stained both in the nucleus
      and in the cytoplasm, which indicated the presence of the virus in both
      subcellular compartments. Our observations suggest that saliva cells, lymphocytes
      and epithelial cells, may potentially participate in oral transmission of HTLV-I.

PMID- 9645209
TI  - [Proliferation and apoptosis before and after preoperative simultaneous
      radiochemotherapy of rectal carcinomas].
AB  - PURPOSE: To investigate the relationship between apoptotic cell death,
      proliferative activity, and the status of the tumor suppressor gene p53 in rectal
      cancer before and after radiochemotherapy. MATERIALS AND METHODS: Thirty-two
      patients dispositioned to receive preoperative radiochemotherapy for locally
      advanced rectal carcinoma prior to radical surgical tumor resection were
      analysed. In all cases, pretherapy biopsies and the final resected specimens
      after radiochemotherapy were available for analyses. Apoptotic cells were
      identified and quantified using in situ end labeling (ISEL) technique. The
      proliferative activity was determined by immunohistochemical assessment of the
      Ki67 (MIB-1) antigen. p53 expression was analysed immunohistochemically as well.
      A clinical-to-pathologic downstaging after radiochemotherapy was achieved in
      25/32 patients (78%). In one case, no residual tumor was detected after
      radiochemotherapy. RESULTS: After radiochemotherapy, the apoptotic index
      increased significantly in almost every case examined. In contrast, the
      proliferative activity was significantly decreased when comparing biopsies and
      resected specimens. Tumors that were immunohistochemically negative for p53
      generally exhibited a higher apoptotic index than p53 positive tumors. However,
      we did not find any correlation between the (pre- and post-therapeutic) rate of
      apoptosis and the degree of clinical-to-pathologic downstaging. CONCLUSION: Our
      results indicate, that radiochemotherapy induces an increase in apoptotic cell
      death. The observation of higher rates of apoptosis in p53 negative tumors
      suggests that p53 might be a regular of apoptosis in rectal cancer.

PMID- 9645211
TI  - [Predictive significance of reflex otalgia in local radical radiotherapy of
      oropharyngeal carcinomas].
AB  - BACKGROUND: Patients with carcinomas of the upper aero-digestive tract often
      suffer from ear pain as a tumor associated syndrome. This prospective study
      examines the predictive and prognostic value of this symptom. PATIENTS AND
      METHODS: Ninety-six consecutive patients who completed a locally radiotherapy of
      a carcinoma of the oropharynx were prospectively evaluated and followed. Forty
      nine out of 96 patients stated the symptom, either spontaneously or after
      questioning. The 2 groups showed no difference regarding TNM-classification,
      histology and total dose. Overall survival, local control and disease specific
      survival were calculated according to Kaplan-Meier and compared by the log-rank
      test. RESULTS: A clinically complete remission was obtained in significantly
      fewer patients with reflex-otalgia as compared to patients without reflex
      otalgia, 61.2% versus 89.3%, p < 0.002. Local control of patients with reflex
      otalgia was significantly less with 49%, mean follow-up 564 days, in comparison
      to local control in patients without reflex-otalgia, mean follow-up 613 days, p =
      0.01. Disease specific survival was significantly worse for patients with reflex
      otalgia, p < 0.012. The probability of local control of T1/T2 tumors with reflex
      otalgia was similar to T3/T4 tumors without reflex-otalgia. Local control for all
      tumor categories combined is 74% for patients without reflex-otalgia versus 49%
      for patients with reflex-otalgia. CONCLUSION: In our patients, reflex-otalgia is
      a new and statistically significant parameter for the probability of local
      control and disease specific survival.

PMID- 9645210
TI  - [Treatment of stage IIIB loco-regionally advanced non-small-cell bronchial
      carcinomas with radiation and interferon-beta. Preliminary results of a phase II
      study].
AB  - BACKGROUND: In-vitro and in-vivo studies demonstrated the radiosensitizing effect
      of interferon beta on malignant tumor tissue as well as simultaneously a
      radioprotective effect on normal lung tissue. In this phase II study the outcome
      of combining radiotherapy with interferon beta in patients with advanced non
      small cell lung cancer was evaluated. PATIENTS AND METHOD: From February 1994
      until November 1996 14 patients with non-small cell lung cancer, stage IIIB were
      treated with locoregional radiation up to 59.4 Gy, with daily doses of 1.8 Gy and
      5 fractions per week. Five million units of interferon beta (Fiblaferon) were
      given intravenously immediately preceding radiotherapy on the first 3 days of
      week 1, 3 and 5. RESULTS: Four of 14 patients (28.6%) showed complete response
      and 7 patients (50%) partial response, resulting in an overall response rate of
      78.6%. After a mean follow-up time of 23.3 months the 1-, 2- and 3-year survival
      rates were 56.3%, 37.5% and 37.5%, respectively. The median survival time was 13
      months. Three of 14 patients (21.4%) suffered from 7 Grade-3 acute side effects
      and 2 patients (14.3%) from 1 Grade-3 late toxicity in each case. One further
      patient, whose right lung was resected 3 months after completion of radiotherapy,
      developed as a consequence of this operation 2 Grade-4 complications. CONCLUSION:
      Considering the toxicity and the preliminary results of combining irradiation and
      interferon beta in the treatment of locally advanced non-small cell lung cancer
      it seems, that this procedure is worth to be tested in a phase III study.

PMID- 9645212
TI  - [Primary radiotherapy of recurrent Merkel cell carcinoma of the eyelid. Case
      report and review of the literature].
AB  - BACKGROUND: Despite an increasing number of reports Merkel-cell-carcinoma still
      is a rare neoplasm. Reports on radical radiotherapy are sparse. PATIENT AND
      METHOD: We report on a successful radical radiotherapy of a recurrent Merkel-cell
      carcinoma of the eyelid in an 84-year old woman, using a hypofractionated
      treatment of 50 Gy with 70 kV-X-rays, 10 fractions of 5 Gy within 5 weeks.
      RESULT: Rapid and complete remission was achieved, with no signs of local or
      distant failure 24 months after the end of therapy. CONCLUSION: The case reported
      on highlights the radiosensitivity of this tumor and the role of radiotherapy not
      merely as salvage procedure.

PMID- 9645213
TI  - Comparison of the response of human FaDu squamous cell carcinoma in nude mice
      after hypofractionated-accelerated regimens and "curative" fractionation
      schedules.
AB  - BACKGROUND: It has been suggested that tumors respond differently after
      irradiation with 10 or more fractions than with less fractionated regimens and
      that extrapolation from experiments with only a few fractions to "curative"
      regimens may be invalid. To test this hypothesis, we compared hypofractionated
      accelerated treatments with "curative" fractionation schedules in human squamous
      cell carcinoma in nude mice. MATERIAL AND METHODS: FaDu tumors were transplanted
      subcutaneously into the hindleg of NMRI nu/nu mice. TCD50 values, i.e., the dose
      necessary to control 50% of the tumors locally, were determined after irradiation
      under ambient blood flow conditions with 5 and 10 fractions in 5 days, 10
      fractions in 10 days, and 30 fractions in 15 days, 6 weeks or 10 weeks. RESULTS:
      TCD50 values of the hypofractionated regimens were not significantly different
      and varied from 41 to 46 Gy. The number of fractions given in the same overall
      time had no measurable effect on local tumor control. The TCD50 after 30
      fractions in 6 weeks was 30 Gy higher than after the hypofractionated regimens.
      This effect was caused by a substantial increase of TCD50 with overall treatment
      time, the dose recovered per day was 0.82 Gy (95% CI 0.66; 0.96). alpha/beta eff
      determined from all data was 58 Gy (13; infinite). CONCLUSIONS: The results of
      the present study compare well with our previous findings after different
      "curative" fractionation schedules in the same tumor. Thus, our study does not
      support that tumors respond differently after application of 10 or more fractions
      compared to less fractionated regimens. The biological mechanisms that govern the
      radiation response of FaDu tumors appear to be the same for hypofractionated
      accelerated and "curative" regimens. Since only one tumor was investigated, these
      results cannot be generalized at the present time.

PMID- 9645214
TI  - [Analysis of different application systems and CT-controlled planning variants in
      treatment of primary endometrial carcinomas. Is brachytherapy treatment of the
      entire uterus technically possible?].
AB  - BACKGROUND: Intracorporal brachytherapy is regarded as the definitive component
      of treatment for inoperable patients with endometrial carcinoma. Until now the
      whole uterus has been claimed to represent the target volume independent of
      individual tumor spread. The purpose of this work is to analyse the correlation
      between target volume and treated volume using different application- and
      planning procedures. PATIENTS AND METHODS: In a consecutive series of 10 patients
      with primary irradiated endometrial carcinoma we analyzed the correlation between
      target volume and treated volume using either standard 1-channel applicators or
      individual Heyman-applicators. Application of the ovoids was followed by a
      planning CT scan for all patients. Based on this, target volume (uterus volume)
      was estimated on a 3D-planning system. According to the measurable length of the
      uterus cavity we determined the corresponding standard 1-channel applicator and
      calculated the respectively treated volume. Estimating the advantages of an
      optimized treatment planning strategy for individual Heyman-applications were
      compared the treated volumes, which result from a standardized and optimized
      treatment planning procedure. RESULTS: The mean uterus volume was 180 cm3 (range
      57 to 316 cm3). Asymmetric uterus configurations with longitudinal or sagittal
      side differences exceeding 1 cm were found in 40% of the cases. Using standard 1
      channel applicators on average 47% (range 25 to 89%) of the uterus volume were
      enclosed by the treated volume compared to 70% for Heyman-applications.
      Differentiating these individual applications according to the variable treatment
      modality values of mean 66% (range 36 to 110%) for the standardized and 73%
      (range 48 to 95%) for the optimized treatment planning strategy were found.
      Moreover optimized planning modalities led to an improved coverage of the target
      volume in 5 out of 10 cases with an increase in volume of 20% on average (range
      11 to 32%). In 3 cases changes of less than 5% were noticed (no improvement). In
      order to protect organs at risk treated volume had to be decreased in 2 cases for
      19% and 40% respectively. CONCLUSIONS: Intracavitary brachytherapy of primary
      endometrial carcinoma was improved by individualized application- and planning
      procedures, which led to better adaptations of the treated volumes to the target
      volumes. Nevertheless a complete coverage--corresponding to the primary intent-
      was not possible. Individualized and optimized brachy-therapy must be performed
      according to the individual tumor spread and uterus configuration. Therefore,
      different applicators are required.

PMID- 9645215
TI  - [Dose-volume histograms and 3-D planning in breast-saving therapy of breast
      carcinoma].
AB  - AIM: Improvement of the dose homogeneity in radiation treatment of the intact
      breast using 3D-planning and dose volume histograms. PATIENTS AND METHOD: 3D
      planning, including the calculation of dose volume histograms of the planning
      target volume, was performed on 15 patients, who underwent radiation therapy with
      tangential photon beams. A standard plan and 2 modified or optimized plans were
      evaluated. Different dosimetric parameters like maximum dose, mean dose, standard
      deviation and the fractional volume which receives doses from 95 to 105% of the
      reference dose were compared and correlated with breast size. RESULTS: With
      increasing breast size standard planning leads to increased overdosage, both in
      magnitude and volume. Individual optimization by modifying weights and wedges
      gives no improvement in dose homogeneity, whereas a photon energy of 10 MV
      results in a more homogeneous dose distribution. The drawback of the higher
      energy is the increased underdosage of the skin. CONCLUSION: Using the standard
      geometry of tangential fields the dose homogeneity cannot be improved
      significantly by 3D-planning, compared to our standard technique.

PMID- 9645216
TI  - [Oral sucralfate administration for therapy and prevention of radiation-induced
      esophagitis: results of a placebo-controlled double-blind study].

PMID- 9645217
TI  - [Late toxicity after allogeneic bone marrow transplantation in children in
      relation to conditioning regimen: whole body irradiation versus busulfan].

PMID- 9645218
TI  - [Alternating radiochemotherapy in bladder carcinomas].

PMID- 9645219
TI  - [Anti-angiogenetic therapy of tumors in the animal experiment].

PMID- 9645220
TI  - Retrotransposable elements in the Dictyostelium discoideum genome.
AB  - Repetitive DNA is a major component of any living cell. In eukaryotes
      retrotransposable elements make up several percent of the genome size, and
      consequently, retroelements are often identified in experiments aimed at
      establishing physical maps and whole genome sequences. In this review, recent
      progress in the characterization of retrotransposable elements in the genome of
      the eukaryotic microorganism Dictyostelium discoideum is summarized with a focus
      on retroelements which integrate near transfer RNA genes with intriguing position
      specificity.

PMID- 9645221
TI  - Screening of conformationally constrained random polypeptide libraries displayed
      on a protein scaffold.
AB  - The selection of novel proteins or enzymes from random protein libraries has come
      to be a major objective in current biology, and these enzymes should prove useful
      in various biological and biomedical fields. New technologies such as in vitro
      selection of proteins in cell-free systems have high potential to realize
      evolutionary molecular engineering of proteins. This review highlights an
      application of insertional mutagenesis of proteins to evolutionary molecular
      engineering. Random sequence proteins are inserted into the surface of a host
      enzyme which serves as a scaffold to display random protein libraries.
      Constraints on random polypeptide conformations owing to the proximity of N- and
      C-termini on the scaffold would result in greater screening efficiency of
      libraries. The scaffold enzyme is also used as a probe for monitoring the hill
      climbing of random sequence proteins on a fitness landscape and navigating rapid
      protein folding in the sequence space.

PMID- 9645222
TI  - Mechanisms of resistance to xenobiotics in human therapy.
AB  - Xenobiotic resistance is the major cause of failure in human therapies. Because
      of their serious clinical and economical consequences, resistance phenomena have
      been intensively studied in the case of antibacterial, anticancer, antipaludic
      and anti-human immunodeficiency virus-1 therapies. Beside pharmacological factors
      that can impede the action of the drugs, several cellular mechanisms of
      resistance have been described. Surprisingly, these mechanisms are conserved
      among bacteria, eucaryotic cells, parasites and viruses. The efficiency of drugs
      can be circumvented by alteration of the drug cellular concentration (altered
      influx, enhanced efflux or sequestration), detoxification, alteration of the drug
      target, nonactivation or inactivation of the drug, or by enhanced DNA repair.

PMID- 9645223
TI  - Mechanisms controlling cellular suicide: role of Bcl-2 and caspases.
AB  - Apoptosis is an essential and highly conserved mode of cell death that is
      important for normal development, host defense and suppression of oncogenesis.
      Faulty regulation of apoptosis has been implicated in degenerative conditions,
      vascular diseases, AIDS and cancer. Among the numerous proteins and genes
      involved, members of the Bcl-2 family play a central role to inhibit or promote
      apoptosis. In this article, we present up-to-date information and recent
      discoveries regarding biochemical functions of Bcl-2 family proteins, positive
      and negative interactions between these proteins, and their modification and
      regulation by either proteolytic cleavage or by cytosolic kinases, such as Raf-1
      and stress-activated protein kinases. We have critically reviewed the functional
      role of caspases and the consequences of cleaving key substrates, including
      lamins, poly(ADP ribose) polymerase and the Rb protein. In addition, we have
      presented the latest Fas-induced signalling mechanism as a model for receptor
      linked caspase regulation. Finally, the structural and functional interactions of
      Ced-4 and its partial mammalian homologue, apoptosis protease activating factor-1
      (Apaf-1), are presented in a model which includes other Apafs. This model
      culminates in a caspase/Apaf regulatory cascade to activate the executioners of
      programmed cell death following cytochrome c release from the mitochondria of
      mammalian cells. The importance of these pathways in the treatment of disease is
      highly dependent on further characterization of genes and other regulatory
      molecules in mammals.

PMID- 9645224
TI  - The structure and function of platelet-activating factor acetylhydrolases.
AB  - Platelet-activating factor acetylhydrolases (PAF-AHs, EC 3.1.1.47) constitute a
      unique and biologically important family of phospholipase A2s. They are related
      to neither the well-characterized secretory nor cytosolic PLA2s, and unlike them
      do not require Ca2+ for catalytic activity. The distinguishing property of PAF
      AHs is their unique substrate specificity: they act on the phospholipid platelet
      activating factor (PAF), and in some cases on proinflammatory polar
      phospholipids, from which they remove a short acyl moiety--acetyl in the case of
      PAF--located at the sn-2 position. Because PAF is found both in the plasma and in
      the cytosol of many tissues, PAF-acetylhydrolases are equally widely distributed
      in an animal organism. Recent crystallographic studies shed new light on the
      complex structure-function relationships in PAF-AHs.

PMID- 9645225
TI  - Drug susceptibility of PCA in WBB6F1-W/Wv mice.
AB  - Our previous study revealed that passive cutaneous anaphylaxis (PCA) can be
      produced in congenitally mast cell-deficient WBB6F1-W/Wv (abbreviated as W/Wv)
      mice on sensitization with undiluted or slightly diluted allogeneic and
      xenogeneic antisera but not on sensitization with allogeneic monoclonal
      immunoglobulin (Ig)E and IgG1 antibodies regardless of the antibody concentration
      [1]. In view of these findings, the present study was conducted to characterize
      PCA in this strain from its drug susceptibilities using mast cell-bearing WBB6F1
      (+)/+ (abbreviated as +/+) and B6D2F1 mice as references. PCA in W/Wv mice
      mediated by a low dilution (1:4) of hyperimmune serum to bovine serum albumin of
      the B6D2F1 mouse origin was markedly suppressed by CV-6209, an antagonist of
      platelet-activating factor (PAF), but not by antihistamines such as
      cyproheptadine and oxatomide. In contrast, PCA in +/+ and B6D2F1 mice mediated by
      a high dilution (1:128) of the anti-serum (virtually by IgG1 antibody) was nearly
      completely suppressed by antihistamines but not by CV-6209. A remarkable
      difference between PCA in W/Wv and reference mice was also observed in the
      susceptibility to monoclonal anti-mouse granulocyte (Gr-1) antibody: PCA in W/Wv
      mice was potently suppressed by the 1- to 3-day pretreatment with this antibody
      but that in references was not at all. Putting these present results together
      with the previous finding that anti-granulocyte antibody greatly reduces
      circulatory Gr-1+ leukocytes, 1 to 3 days after the treatment [2], it is highly
      probable that PCA in W/Wv mice mediated by some antibody isotypes other than IgE
      and IgG1 is produced by PAF mainly released from Gr-1+ cells, while IgG1 antibody
      mediated PCA in mast cell-bearing reference mice is evoked by histamine derived
      from mast cells. PCA homologous to that in W/Wv mice could also be produced in
      the reference mice on sensitization with undiluted or slightly diluted antiserum,
      when generalized blueing due to excess IgG1 antibody was removed by the oxatomide
      treatment before the antigen challenge.

PMID- 9645226
TI  - Regulation of rhythmic melatonin production in pineal cells of chick embryo by
      cyclic AMP.
AB  - The pineal cells of chick embryos incubated in vitro exhibited a daily rhythm of
      melatonin synthesis under a 12:12 light:dark (LD) cycle at the embryonic days 16
      and 19. In order to elucidate whether cyclic adenosine monophosphate (cAMP)--a
      component of the melatonin generating system--is already at work in the embryonic
      period, we measured the effects of forskolin and isobuthylmethylxantine (IBMX) on
      melatonin production, cAMP efflux and accumulation. Forskolin (after 10, 20, 30,
      45, 60 and 90 min of administration) and IBMX (6 h), when applied during the
      light phase of LD cycle, stimulated melatonin production and cAMP efflux and
      accumulation during the embryonic period (at days 16 and 19 fo development). Our
      results suggest that the biochemical pathway involving cAMP, which controls
      melatonin production in the postnatal period, is developed before hatching and
      already on embryonic day 19 works in a way similar to that in post-hatched
      chicks. Differences in response to cAMP stimulation between 16- and 19-day-old
      pinealocytes seem to be mostly quantitative.

PMID- 9645227
TI  - Antimicrobial activity in the skin of the channel catfish Ictalurus punctatus:
      characterization of broad-spectrum histone-like antimicrobial proteins.
AB  - Three antibacterial proteins were isolated from acid extracts of channel catfish
      (Ictalurus punctatus) skin by cation exchange chromatography and reverse-phase
      high-pressure liquid chromatography. The molecular masses of the proteins were
      15.5, 15.5 and 30 kD as determined by SDS-polyacrylamide gel electrophoresis.
      Mass spectrometry, amino acid composition and amino acid sequence data suggest
      that the most abundant protein is closely related to histone H2B. The H2B-like
      protein was inhibitory to Aeromonas hydrophila and Saprolegnia spp., which are
      important bacterial and fungal pathogens of fish. These findings suggest that
      histones may be important defensive molecules in fish.

PMID- 9645228
TI  - Dictyostelium discoideum cells shed vesicles with associated DNA and vital stain
      Hoechst 33342.
AB  - Dictyostelium discoideum cells are highly resistant to xenobiotics. We previously
      observed that these primitive eukaryotic cells contain a 170-kDa P-glycoprotein,
      mediating multidrug resistance in mammalian cells, but nonfunctional in
      Dictyostelium cells. We show here that D. discoideum cells vitally stained with
      the DNA-specific dye, Hoechst 33342, release fluorescent material in their
      culture medium. Electron microscopy and lipid analysis demonstrate the vesicular
      nature of this material. Moreover, nucleic acids associate with these
      extracellular vesicles independently of Hoechst vital staining. The main
      vesicular DNA component exhibits a size > 21 kb. Shedding of microvesicles during
      cell growth is not concomitant with programmed cell death. We propose that these
      extracellular vesicles are involved in a new cellular resistance mechanism
      against xenobiotics. Furthermore, since the association of DNA with vesicles
      occurs in physiological growth conditions and independently of vital staining,
      the new shedding process might be involved in a more general intercellular
      mechanism.

PMID- 9645229
TI  - [Establishment of the Mendel Institute].

PMID- 9645230
TI  - Bioethical considerations on cloning and twinning.

PMID- 9645231
TI  - From genetic research into clinical practice.
AB  - The present genome era is characterized by speedy progress and prompt transfer of
      results into clinical practice. This creates the need for rapid disclosure of
      results and renewal of laboratory's protocols. Molecular cytogenetics has
      provided and increased ability to identify chromosomes, correlate chromosome
      structure with gene location, find out cryptic aberrations, and detect specific
      DNA sequences. These advances have allowed the confident discovery of a number of
      contiguous gene syndromes. The positional cloning and positional candidate
      strategies have greatly expedited the search process of disease genes, and become
      relevant methods for genes' discovery. Understanding the molecular basis of
      diseases has shown an unpredicted wide genetic heterogeneity, which has splitted
      single disorders into many clinically similar conditions, and added complexity to
      the nosology of human diseases. The opposite process, allelism, where clinical
      diversity results from allelic mutations, has lumped together many distinct
      disorders, by showing that different clinical entities are not necessarily due to
      mutations in different genes. Dynamic mutations have provided the molecular
      understanding of interindividual and intrafamilial variability including
      anticipation, in a number of diseases. The discovery of distinct correlations
      between the molecular pattern and disease severity is providing a unique
      opportunity for using molecular results to assess the clinical outcome.
      Diagnostic, presymptomatic and predictive molecular testing are becoming widely
      used and provide enormous opportunities for improving the lot of our patients.

PMID- 9645232
TI  - Twin zygosity diagnosis by mailed questionnaire below age twelve months. Le
      Groupe Romulus.
AB  - Parents of a sample of 76 same sexed pairs of twins aged 3 to 9 months completed
      a mailed similarity questionnaire. It included the Bonnelykke et al.'s
      questionnaire and a four anthropological variable scale. To improve each of these
      two methods, three other combined methods were carried out and results were
      compared with the biological zygosity diagnosis. The Bonnelykke et al.'s
      classification combined with anthropological scale (method 4) gave only 1.2%
      misclassified in the whole sample. It is concluded that zygosity diagnosis using
      this type of procedure to distinguish MZ and DZ pairs would be important not only
      for epidemiological study but also for pediatricians and parents.

PMID- 9645233
TI  - Maternal nutrition in twin gestations: weight gain, cravings and aversions, and
      sources of nutrition advice.
AB  - BACKGROUND: Maternal nutrition has a strong influence on singleton and twin
      birthweight. This study evaluated the association between twin birthweight and
      maternal pregravid body mass index (BMI), weight gain, and cravings and
      aversions. Information was also obtained regarding sources of nutrition advice
      and advised versus actual weight gain. METHODS: This study is based on data from
      interviews with 928 mothers of twins. Univariate analysis included comparisons by
      source of nutritional advice, birthweight categories, and categories of cravings
      and aversions. Multiple logistic regression was used to formulate models for mean
      twin birthweights > 1,500 g and > 2,500 g. RESULTS: Mothers who received their
      nutrition advice from a registered dietitian had the highest weight gains and the
      lowest proportion of birthweights < 1,500 g. For mean twin birthweight > 2,500 g,
      the final model included prematurity, pregravid BMI, and weight gain; for
      birthweights > 1,500 g, the model additionally included maternal age and
      aversions. CONCLUSIONS: Maternal pregravid BMI and gestational weight gain were
      shown to be important factors influencing twin birthweight. Nutrition advice,
      particularly from a registered dietitian, may be vital in assuring adequate
      weight gain, and therefore better birthweights, for these high-risk pregnancies.

PMID- 9645234
TI  - Very early and simple determination of chorionic and amniotic type in twin
      gestations by high-frequency transvaginal ultrasonography.
AB  - OBJECTIVE: The aim was to determine the chorionic and amniotic types in
      multifetal pregnancies with transvaginal ultrasonography at very early stage of
      gestation. STUDY DESIGN: Twenty-one spontaneous multifetal pregnancies were
      scanned transvaginally before 8 weeks' gestation (four of them from 4th week).
      The chorionic and amniotic type was determined ultrasonographically. All twin
      gestations had postpartum pathologic evaluation of the placenta and histologic
      determination of the chorionic and amniotic type. RESULTS: Ultrasonographic
      evaluation of the 21 pregnancies demonstrated 20 twin and 1 triplet gestation.
      Four of the twin pregnancies were monochorionic-diamniotic. Triplet was
      monochorionic-triamniotic (spontaneously aborted in 8th week of gestation). In
      all 20 twin pregnancies, transvaginal ultrasonography correctly predicted the
      chorionic and amniotic type before 8 weeks of gestation. CONCLUSION: Transvaginal
      ultrasonography allows a reliable, simple and rapid determination; the
      dichorionic twin pregnancy in 4 weeks, monochorionic in 5 weeks, and
      differentiation of mono- or diamniotic in 7 weeks of gestation.

PMID- 9645235
TI  - Perinatal outcome after leave of absence from work for twin-pregnant women.
AB  - AIM: To evaluate the association between the incidence of leave of absence from
      work and perinatal outcome for the twin-pregnant woman. MATERIAL AND METHODS: A
      20.2% sample of all twin-pregnant women between 1982 and 1988 (1,331/6,602) was
      taken at random from the entire material of twin deliveries in Sweden, archived
      at the Medical Birth Registry (MBR), National Board of Health and Welfare. For
      each woman in the sample, information on period(s) and reasons for leave of
      absence from work during pregnancy was obtained by inquiry to all Regional Health
      Insurance Offices throughout Sweden. A comparison of perinatal outcome was also
      made with information from the Danish Fertility Database and the Norwegian
      Medical Birth Registry. RESULTS: Duration of leave from work increased from 58
      days in 1982 to 97 days in 1988 (trend analysis; t = 7.9, p < 0.001). No
      association was seen between perinatal mortality for twins weighing < 1,500 g and
      changes in the incidence of leave of absence. The incidence of twins with a
      birthweight < 1,500 g varied among the three countries, increasing significantly
      only in Sweden (trend analysis chi 2 = 20.3, p < 0.0001). CONCLUSION: Although
      the number of days of leave of absence increased by 60%, there was no obvious
      association with perinatal mortality for twins weighing < 1,500 g. The incidence
      of Swedish twins with a birthweight < 1,500 g increased significantly, indicating
      that the effect of leave of absence from work on perinatal outcome may be less
      effective than previously thought.

PMID- 9645236
TI  - Laurence-Moon-Bardet-Biedl syndrome. Clinical, electrophysiological and genetic
      aspects.

PMID- 9645237
TI  - Detection of Japanese encephalitis virus by reverse transcription/polymerase
      chain reaction.
AB  - A simple and rapid reverse transcription/polymerase chain reaction (RT-PCR) assay
      for detection of Japanese encephalitis virus (JEV) envelope (E) gene sequences in
      various biological samples is described. The assay successfully amplified JEV E
      gene sequences from infected cell cultures, Aedes aegypti larvae, mosquitoes and
      mouse blood. The sensitivity of the assay was currently 1 ng of JEV RNA and could
      be increased up to 1 pg on the background of 1 microgram of cellular RNA by
      biotinylation of the PCR product, Southern blot analysis and
      streptavidin/alkaline phosphatase detection.

PMID- 9645238
TI  - Genetic heterogeneity of Phthorimaea operculella granulovirus: restriction
      analysis of wild-type isolates and clones obtained in vitro.
AB  - Genetic heterogeneity of a wild-type granulovirus (Tunisia isolate) of the potato
      tuber moth Phthorimaea operculella (Phthorimaea operculella granulovirus, Phop
      GV) has been studied. The heterogeneity was indicated by the presence of several
      submolar fragments in the profiles obtained by use of several restriction
      endonucleases. It was also demonstrated by variations in the restriction profile
      of the wild-type Tunisia isolate that had underwent since 1991 in our laboratory
      numerous passages in vivo. A comparison of the Tunisia isolate used in Egypt in
      the biological control programme with other PhopGV isolates indicated that it
      could not be related to any of the 3 genotypes previously defined. Five clones
      obtained from the Tunisia isolate in vitro were further grown both in vitro and
      in vivo. The restriction analysis of these clones demonstrated that none of them
      was identical to the parental wild type virus and to any other PhopGV geographic
      isolates. Genotypic differences between the clones were also shown. A 19 kbp
      BamHI fragment absent in the original Tunisia isolate but present in its passages
      since 1995 at a submolar concentration, was always present at a molar
      concentration in its clones. The presence of this fragment reflects probably a
      selection of one or more variants present in the original isolate and its
      possible adaptation to the growth in our laboratory conditions.

PMID- 9645239
TI  - Prevalence of mutant CCR5 allele in Slovenian HIV-1-infected and non-infected
      individuals.
AB  - A 32 bp deletion in the CCR5 gene designated CCR5 delta 32 has been identified
      recently as the cellular basis for resistance to human immunodeficiency virus
      type 1 (HIV-1) in some individuals which remained non-infected despite a repeated
      exposure to this virus. The prevalence of this deletion was examined by
      polymerase chain reaction (PCR) on 51 HIV-1-infected and 385 non-infected
      individuals from all parts of Slovenia. 84.4% of the the HIV-1-infected and 83.2%
      of the non-infected individuals were homozygous for wild type CCR5, and 19.6% and
      16.3%, respectively, were heterozygous. No homozygous mutant genotype was
      observed among the HIV-1-infected patients. Of the non-infected individuals, 2
      women (0.5%) were found to harbour the CCR5 delta 32/CCR5 delta 32 genotype only,
      which is, to the best of our knowledge, the lowest prevalence of this particular
      genotype found among Caucasians to date.

PMID- 9645240
TI  - Genomic variations of hepatitis B virus strains in patients chronically
      coinfected with hepatitis B and human immunodeficiency viruses.
AB  - Serum samples from 56 human immunodeficiency virus type 1 (HIV-1)-infected adult
      men were analysed for the presence of hepatitis B virus (HBV) serological
      markers. Two or more samples from each patient, collected over an interval of 1-6
      years, were tested. The antibody against HBV core antigen (anti-HBc) prevalence
      was 79%. Three (5%) patients No. 5, 7, and 9 were chronic carriers of HBV surface
      antigen (HBsAg). HBV DNAs from serial samples of these three patients and from
      two HIV-seronegative control patients were characterised after amplification of
      different genome regions by polymerase chain reaction (PCR). Size and restriction
      analyses of the PCR products showed that samples from patients No. 7 (with
      chronic active hepatitis) and 9 (asymptomatic) contained heterogeneous HBV DNA
      populations. In patient No. 7, HBV DNA contained a precore gene stop codon
      mutation at nucleotide (nt) 1896. In addition, a deletion in the core gene was
      found in a sample collected two years after the onset of acquired
      immunodeficiency syndrome (AIDS). PCR products from serial samples of patient No.
      9 indicated a mixture of HBV DNA molecules that were cloned. Sequencing of the
      pre-S region of the clones and phylogenetic analysis showed that patient No. 9
      was superinfected with three HBV populations of distinct origin, all belonging to
      genotype A. HBV DNA of patient No. 5 (with AIDS) did not present any variability
      during a 6-year follow-up. Although two of three HIV/HBV coinfected patients
      harboured heterogeneous HBV DNA populations during the follow-up, no common event
      with respect to HBV DNA evolution was observed among the coinfected patients.

PMID- 9645241
TI  - Electron microscopic examination of Aedes albopictus clone C6/36 cells infected
      with dengue virus 2 at elevated incubation temperature.
AB  - Morphological changes such as loss of cytoplasm, membrane destruction and
      vacuolar swelling in Aedes albopictus clone C6/36 cells infected with dengue
      virus 2 (DV-2) New Guinea B strain and incubated at 28 degrees C and 37 degrees
      C, were observed under electron microscope. Both infected and uninfected cells
      showed significant damage at 37 degrees C in contrast to normal appearance at 28
      degrees C. A higher number of virus particles were observed in the cytoplasm at
      37 degrees C than at 28 degrees C.

PMID- 9645242
TI  - Syn strains HSZP and ANGpath [correction of ANG] of herpes simplex virus type 1
      do not contain mutations in the regions of UL53 gene relevant to syncytium
      formation.
AB  - Parallel sequencing of UL53 gene of four strains of herpes simplex virus type 1
      (HSV-1), two of which (HSZP and ANGpath) were of the syn phenotype while another
      two (KOS and 17) were of the non-syn phenotype, showed in three strains amino
      acid mutations unrelated to the already described syn1 glycoprotein K (gK)
      mutations (Dolter et al., 1994). The only mutations which altered encoded amino
      acids were found in strains HSZP (Gln to Arg at position 198) and ANGpath (Val to
      Ile at position 137). Both mutations were localised outside of the two mutation
      clusters suspected for affecting syncytium formation. In addition, a CG/GC
      variation was found at positions 245-246 and 669-670. These compressions affected
      three codons altering amino acids (aa) 82 (Cys or Ser), 223 (Me or Ile) and 224
      (Leu or Val), respectively.

PMID- 9645243
TI  - Interleukin-9 receptor alpha chain mRNA formation in CD8+ T cells producing anti
      human immunodeficiency virus type 1 substance(s).
AB  - A search for gene(s) associated with anti-human immunodeficiency virus type 1
      (HIV-1) activity of CD8+ T cells was attempted using molecular cloning and the
      relation between the anti-HIV activity of CD8+ T cells and the interleukin-9
      receptor alpha chain (IL-9R-alpha) mRNA expression from the cDNA clones obtained
      was examined. The anti-HIV-1 activity of CD8+ T cell culture supernatants was
      assessed by measuring the level of HIV-1 replication of a CD4+ T cell line
      transfected with an infectious HIV-1 DNA clone. IL-9R-alpha mRNA was assayed by
      reverse transcriptase-polymerase chain reaction (RT-PCR). Of 5 cases showing high
      level of anti-HIV-1 activity (more than 80% suppression of HIV-1 replication),
      the mRNA was detected in 4 cases. Of 10 cases showing low level of anti-HIV-1
      activity (less than 80% suppression of HIV-1 replication), the mRNA was detected
      in one case. Soluble recombinant human IL-9 receptor (rhIL-9sR) did not suppress
      HIV-1 replication at a concentration of 1 microgram/ml. These data suggest that
      the IL-9R-alpha mRNA formation in CD8+ T cells may correlate with and play some
      role in the anti-HIV-1 activity of CD8+ T cells from HIV-1-infected individuals.

PMID- 9645244
TI  - Characterisation of rearranged NSP5 gene of a human rotavirus.
AB  - An atypical human rotavirus strain Z10262, isolated from a chronically infected
      immunodeficient child, displayed an unusual genomic RNA electrophoretic pattern.
      Besides, Northern blot analysis indicated that this strain contained an
      abnormally migrating gene 11 equivalent. Sequencing of this gene showed that it
      was derived from a genetic rearrangement which involved a partial duplication of
      the open reading frame (ORF) encoding the non-structural protein NSP5. However,
      the duplicated region contained a deletion and several point mutations relative
      to the first copy of the ORF. Phylogenetic analysis of human and animal NSP5
      amino acid sequences including Z10262 revealed two groups of human proteins
      related to different animal proteins. The isolation and analysis of Z10262 strain
      provides further evidence for the genetic complexity of naturally occurring human
      rotaviruses.

PMID- 9645245
TI  - Detection of Rickettsia sibirica in ticks and small mammals collected in three
      different regions of China.
AB  - The primers Rr 190.70p and Rr 190.602n were used to detect spotted fever group
      (SFG) rickettsiae by polymerase chain reaction (PCR) in ticks and small mammals
      collected in three different regions of China. The obtained results indicated
      that specific DNA fragments of SFG rickettsiae were amplified from Dermacentor
      silvarum, D. sinicus, D. auratus, Haemaphysalis concinna, H. wellingtoni, H.
      yeni, Apodemus agrarius, Microtus fortis. Clethrionomys rufocanus, Ondatra
      zibethica, Rattus flavipectus and hedgehog. The PCR product were digested with
      restriction endonucleases PstI and RsaI and the obtained electrophoretic profiles
      were compared with those of the prototype strains of SFG rickettsiae by the
      restriction fragment length polymorphism (RFLP) technique. The comparisons showed
      that the profiles were identical to those of Rickettsia sibirica. In addition,
      three new isolates of R. sibirica were obtained from H. yeni, D. sinicus and
      hedgehog, and designated NH-95, BJ-95 and BHJ-95, respectively. These results not
      only demonstrated a horizontal transmission of the rickettsiae between ticks and
      hosts but also suggested that R. sibirica is widely distributed in China and its
      hosts and vectors are various, all that indicating the existence of natural foci
      of North Asia tick-borne spotted fever specific to China.

PMID- 9645246
TI  - [Liver tumors in children: spiral CT findings and differential diagnostic
      classification].
AB  - Liver tumors in childhood are rare. They can be subdivided in benign or primary
      and secondary malignant liver tumors. The prognosis of malignant liver disease
      has improved due to extended therapy in the past few years. Thus, diagnosis of
      liver tumors in childhood gains in significance. After a suspect ultrasound
      diagnosis, usually computed tomography (CT) is used as a radiologic sectioning
      method. Guided by a retrospective analysis of 15 cases, the importance of the
      Helical-CT is presented. Helical-CT is a good diagnostic method for pediatric
      cases due to reduced scan times. By the basis of clinical data, distribution, and
      density, various differential diagnoses can be made. Benign liver tumors,
      especially cysts and frequently haemangioma, can easily be diagnosed and
      controlled because of their typical echogenicity and contrast visualisation. In
      cases of hamartoma, focal nodal hyperplasia, and adenoma computed tomography
      diagnosis is often necessary. Primary malignant liver tumors can prove to be
      unilocular hepatoblastomas or hepatocellular carcinomas, while disseminated liver
      invasions usually are considered as metastatic liver tumors of kidney or adrenal
      cancer.

PMID- 9645247
TI  - [Cavitating lung lesions in the course of ANCA-associated vasculitis:
      differential diagnostic aspects].
AB  - Antineutrophil cytoplasmatic antibodies (ANCA)-associated vasculitides (Wegener's
      granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome) show quite
      variable courses. Clinical features of the full blown generalized systemic
      vasculitis are usually found in the respiratory tract and the kidney. Pulmonary
      involvement of Wegener's granulomatosis shows commonly nodules and cavitations
      but also diffuse alveolar hemorrhage. We report the case of a 57 year-old man
      suffering from dyspnea, thoracal pain, arthralgia, purpura, scleritis and
      tinitus. Specimen of the kidney showed segmental glomerulosclerosis and
      tubulointerstitial nephritis. Because of the presence of cANCA Wegener's disease
      was assumed. Pulmonary infiltrates developed under immunosuppressive treatment
      with cyclophosphamid. As differential diagnosis of the pulmonary infiltrates, we
      considered invasive pulmonary aspergillosis as well as infiltrates due to
      Wegener's granulomatosis. In spite of maximal therapeutic management of patient
      died of respiratory and cardiovascular failure. The findings at autopsy showed
      distinct invasive pulmonary aspergillosis and perifocal hemorrhage.

PMID- 9645248
TI  - [Imaging tumor extension of renal cell carcinomas with magnetic resonance
      tomography. Improved tumor-tissue contrast with Gd-DTPA-assisted spin-echo
      sequences and simultaneous fat suppression].
AB  - PURPOSE: To evaluate the use of contrast-enhanced T1-weighted images with fat
      suppression (T1FS) to improve the contrast-to-noise ratio of renal cancer and
      renal parenchyma as well as perirenal fat. METHODS: 25 patients with
      histologically proven unilateral renal cancer after nephrectomy were examined
      before surgery. In addition to plane and contrast-enhanced T1-weighted as well as
      T2-weighted spin-echo images, all patients had T1 FS immediately after
      administration of Gd-DTPA in two planes. The contrast-to-noise ratio was
      calculated using circular regions-of-interest which outlined the tumor, the renal
      parenchyma, pyelon, and the perirenal fat. RESULTS: T1 FS significantly improved
      the contrast-to-noise ratio of renal cancer and renal parenchyma compared to all
      conventional spinecho sequences (p < 0.001; Wilcoxon-Test). Compared to contrast
      enhanced T1-weighted images without fat-suppression T1 FS yielded a higher CNR of
      the tumor, the perirenal fat and the pyelon. Another advantage was the absence of
      the chemical-shift artifact which is mostly pronounced in T2-weighted images and
      a reduced number of observed artifacts due to breathing. CONCLUSION: T1 FS should
      replace conventional contrast-enhanced T1-weighted spin-echo images in the work
      up of renal cancer using MRI.

PMID- 9645249
TI  - [Calculating the effective dose of occupationally exposed persons in roentgen
      diagnosis].
AB  - The radiation exposure of occupationally exposed staff was measured at tube
      voltages of 50, 80 and 100 kV. A typical arrangement for fluoroscopic
      examinations was chosen: the (standing) physician is exposed by the scattered
      radiation from a (lying) patient. The physician is represented by an Alderson
      Rando-Phantom and a spherical phantom similar to an ICRU sphere. Measurements of
      the partial body dose were performed by film dosimetry in the Alderson-Rando
      Phantom in a.p. and in lateral direction of the scattered radiation respectively.
      From these measurements the effective dose was calculated. The ambient equivalent
      dose H* (10) in the sphere phantom was determined by the same method. The latter
      results yield the conversion factor g, which describes the ratio effective dose E
      to ambient equivalent dose H* (10). A conversion factor of g = 0.3 was
      established by averaging over the tube voltage and the direction of the scattered
      radiation. Based on the guidelines 96/29/Euratom and the transition from old to
      new dose quantities a reduction of the dose limits for occupationally exposed
      persons by a factor of up to 3.75 will be necessary. Applying the conversion
      factors can almost compensate that reduction.

PMID- 9645250
TI  - [Heavy metal incorporation as an unusual self-injury].
AB  - A 19-year-old man was admitted to hospital because of uncharacteristic neurologic
      symptoms. During the first examination morphologic alterations due to an
      injection of mercury into the left arm and the left side of the trunk were found.
      The dose and the manner of application were doubtful and suspected to be a case
      of self-infliction. The man informed the police only 7 months later because his
      relatives had finally persuaded him to do so. The description of the infliction
      by unknown perpetrators was full of contradictions. Initially the patient gave
      only an indistinct description. But later on, the number of details increased. At
      the same time there was a change in the characteristics of the perpetrator(s).
      Other differences existed concerning a loss of consciousness which should have
      been caused by a single stroke on an arm. Furthermore, the patient told about a
      swelling as big as an egg, provoked by an injection of liquid mercury. It could
      be shown by experiments that mercury can be injected into soft-tissue very simply
      and that it spreaded widely. Arguments for a self-injection were e.g. the
      technical possibility, the topography of the injection marks, and an easy
      handling of the syringe. A psychiatric examination furthermore revealed, that the
      patient had had periods of restriction of thinking, sometimes combined with a
      lack of appreciation.

PMID- 9645251
TI  - [Symptomatic heterotopic splenic tissue in the adrenal gland area].
AB  - We report on a 33-year-old man with symptomatic heterotopic suprarenal splenic
      tissue. Heterotopic splenic tissue can often be found after posttraumatic
      splenectomy. It is a result of autotransplantation induced by trauma (splenosis).
      Additionally it can grow during embryogenic development. Such an accessory spleen
      is found in 10-44% of all autopsies. In this case report the patient was treated
      by resection due to increasing flank pain and suspected neoplasm.

PMID- 9645252
TI  - [Emphysematous pyelonephritis].
AB  - Emphysematous pyelonephritisis a relatively rare, gas-producing, destructive and
      usually unilateral renal infection. Often the patients are female diabetics and
      mostly the left kidney is affected. The pathological gas formation is either
      limited to the kidney or extends to the perirenal space. Two cases are reported,
      which-in clinical presentation, extension of pathological gas, and treatment
      present two possible ends of the spectrum of this disease.

PMID- 9645253
TI  - [Endosteal hyperostosis--differential diagnosis and possible therapeutic
      outlook].
AB  - A case report on a 42-year old man with an osteosclerotic bone disorder is
      presented. Physical examination and radiological findings are in favour of
      endosteal hyperostosis. Differential diagnoses are discussed.

PMID- 9645254
TI  - [Primary non-Hodgkin lymphoma of the ovary].
AB  - A young female patient was admitted for clarification of a space-occupying
      ovarian situation. Histological analysis gave the finding of a highly malignant
      NHL of the Burkitt type. In the further course of the disease bicytopenia
      developed. Bone mark analysis revealed a B-AII. FAB L3 which can be considered as
      the leukemic equivalent of the Burkitt lymphoma. In spite of chemotherapy the
      patient died as a consequence of a sepsis.

PMID- 9645255
TI  - [Right-sided double inferior vena cava and common iliac vein: imaging with spiral
      computerized tomography].
AB  - Duplications of the inferior vena cava (IVC) are rare variants of the abdominal
      vessels and are normally located on both sides of the abdominal aorta. The rare
      case of a rightsided infrarenal duplication of the IVC with involvement of the
      common iliac vein is reported. Details of the embryology are presented for the
      understanding of this IVC variant. The spiral CT with multiplanar reconstructions
      makes it possible to define the vascular morphology and to differentiate it from
      lymphoma.

PMID- 9645256
TI  - [Comparison of film-screen combinations in contrast-detail diagram and with
      interactive image analysis. 3: Trimodal histograms of gray scale distribution in
      bar groups of lead pattern images].
AB  - The following four screen film combinations were compared: a) a combination of
      anticrossover film and UV-light emitting screens, b) a combination of blue-light
      emitting screens and film and c) two conventional green fluorescing screen film
      combinations. Radiographs of a specially designed plexiglass phantom (0.2 x 0.2 x
      0.12 m3) with bar patterns of lead and plaster and of air, respectively were
      obtained using the following parameters: 12 pulse generator, 0.6 mm focus size,
      4.7 mm aluminum prefilter, a grid with 40 lines/cm (12:1) and a focus-detector
      distance of 1.15 m. Image analysis was performed using an Ibas system and a Zeiss
      Kontron computer. Display conditions were the following: display distance 0.12 m,
      a vario film objective 35/70 (Zeiss), a video camera tube with a PbO
      photocathode, 625 lines (Siemens Heimann), an Ibas image matrix of 512 x 512
      pixels with a spatial resolution of ca. 7 cycles/mm, the projected matrix area
      was 5000 micron 2. Maxima in the histograms of a grouped bar pattern were
      estimated as mean values from the bar and gap regions ("mean value method"). They
      were used to calculate signal contrast, standard deviations of the means and
      scatter fraction. Comparing the histograms with respect to spatial resolution and
      kV setting a clear advantage of the UVR system becomes obvious. The quantitative
      analysis yielded a maximum spatial resolution of approx. 3 cycles/mm for the UVR
      system at 60 kV which decreased to half of this value at 117 kV caused by the
      increasing influence of scattered radiation. A ranking of screen-film systems
      with respect to image quality and dose requirement is presented. For its
      evaluation an interactive image analysis using the mean value method was found to
      be superior to signal/noise ratio measurements and visual analysis in respect to
      diagnostic relevance and saving of time.

PMID- 9645257
TI  - [Roentgen diagnosis without medical indications and physical injury. Verdict of
      the federal court 3 December 1997--2 StR 397/97].
AB  - An orthopedist had been sentenced for different offenses to two years and six
      months imprisonment by the Landgericht Frankfurt (superior court). One point of
      the ruling had been the evaluation of the use of X-ray methods without medical
      indication, which the Landgericht Frankfurt/Main (superior court) finally did not
      evaluate as bodily harm. The Bundesgerichtshof (supreme court) of Germany
      overruled this interpretation and referred the case back for new trial and
      ruling.

PMID- 9645258
TI  - Usefulness and limitations of PEF.

PMID- 9645259
TI  - A study of allergy to penicillin antibiotics in 1995 in the Child Allergy
      Department of the Gregorio Maranon University hospital.
AB  - We present 219 cases of adverse reactions to penicillin and related antibiotics
      during 1995 in the Child Allergy Department of Gregorio Maranon University
      Hospital. Amoxicillin was the most frequent cause of the reaction. The most
      common clinical symptom was urticaria followed by angio-edema and other
      characteristic exanthemas. A diagnosis of allergy to penicillin and related drugs
      was only made in 20 cases in which the predominant symptomatology was urticaria
      and the antibiotic most commonly involved was again amoxicillin. Diagnosis was
      confirmed by a skin test, specific IgE determination and controlled provocation.
      In 3 of the 20 cases diagnosis was made in the reassessment or second study,
      which was carried out in all cases in which more than one year had passed between
      the reaction and the initial allergological study.

PMID- 9645260
TI  - Assessment of the inhalation technique in asthmatic patients: a comparative study
      of three aerosol devices.
AB  - Local administration of drugs by means of aerosol device is widely used in the
      treatment of asthma. Nevertheless, the effectiveness of this method depends on an
      adequate inhalation technique (IT), which available evidence has shown to be
      rather problematic. The aim of this study was to assess IT in out-patients with
      bronchial asthma who frequently use aerosol therapy with Pressurized Metered dose
      inhalers (MDI), pressurized inhalers with spacer (MDI-S) and the Astra-Draco
      Turbuhaler system (TH). A sample of 150 adults with asthma were evaluated. These
      patients had been followed up for than two years and they often used one of the
      devices mentioned above. The IT has broken down into several steps for each
      procedure. Percentages of patients with one error in the IT were 50%, 44% and 42%
      for MDI, MDI-S and TH procedures, respectively. 18%, 20% and 14% of patients
      committed three errors in the IT, respectively. Differences detected were not
      significant. Seven patients committed errors in every step of the IT. In
      conclusion, the level of errors found in our study is high, similar to that cited
      in the existing literature. It is also roughly equivalent for the three devices
      tested. We believe that the proper teaching monitoring of IT skills is highly
      important in the treatment of bronchial asthma.

PMID- 9645261
TI  - Serum immunoglobulin E levels in relation to adenoid surgery.
AB  - The adenoid tissue is an immunecompetent lymphoid organ, which has the capacity
      of reacting against numerous antigens. We have studied the influence that the
      elimination of the said tissue would have on the total IgE serum levels in 33
      patients of an average age of 5 and criteria of adenoidectomy and in whom these
      levels were measured before and after surgery. We have not noticed any
      statistically significant differences in the IgE values after adenoidectomy with
      respect to those prior to surgery, which were normal. Adenoidectomy, like other
      authors have observed after tonsillectomy, does not alter the IgE serum values.

PMID- 9645262
TI  - Stevens-Johnson syndrome from tetrazepam.
AB  - We present a case of a patient showing a cutaneous and systemic affectation
      compatible with the Stevens-Johnson syndrome due to the intake of tetrazepam as a
      muscular relaxant. The symptoms remitted after the suspension of the involved
      medicines and after treatment with systemic corticoids. Months later, a study
      with patch tests, with the standard battery and the medicines that she took
      (indapamide, tetrazepam, acetyl salicylic acid, botriozolam and levomepromazine)
      was carried out. She presented positivity to tetrazepam at 48 and 96 hours. The
      oral provocations with the other medicines, which she consumed, were negative.
      The study of cross reactivity with other benzodiazepines was negative. In the
      medical literature, different cutaneous affectations regarding benzodiazepine use
      (generalised drug eruptions, contact dermatitis, erythema multiforme, ...) have
      been described byt non Stevens-Johnson syndrome. The patch tests are useful in
      the diagnosis of this type of cutaneous reactions, avoiding in this way the
      achievement of oral provocations, with the potential risk for the patient that
      they imply. The absence of cross-reactions with other substances of the same
      group has to be pointed out, even with those with which keeps great structural
      similarity as the diazepam. In spite of the absence of cross reactions with the
      rest of benzodiazepines, faced with the seriousness of the case presented, it is
      advised to the patient to avoid this type of medicines.

PMID- 9645263
TI  - [Biological and genetic basis of atopy and asthma].
AB  - Atopy is triggered by allergens and enhanced by environmental factors, but it has
      a clear genetic basis, as it is confirmed by the high incidence in siblings and
      twins. In the last few years, many authors have published genetic studies on
      asthmatic and atopic patients, generally with very controversial results. In the
      present article, IgE regulation and other immunological mechanisms which are
      assumed to be involved in the atopic reaction are reviewed. In the second part,
      the coding genes of factors, cytokines and receptors that take part in the atopy
      are commented, as well as review of the recent articles published about genetic
      markers or polymorphisms associated to these genes. The unveilling of the genetic
      background of atopy and asthma is a very difficult task, and it will need the
      definition of a specific atopic phenotype and a clear knowledge of the
      immunologic basis of atopy. Finally, due to racial and geographical variations a
      wide collaborative study of many research groups distributed all over the world
      will be needed.

PMID- 9645264
TI  - Early recognition of pregnancy by the maternal immune system.
AB  - PROBLEM: Immunologic recognition of pregnancy is important for normal gestation.
      Successful pregnancy is characterized by a Th2 dominance, whereas there is a Th1
      dominance in failed pregnancies. We assume that a signal given by the fertilized
      ovum induces a Th2 shift, necessary for a normal outcome. In vitro fertilization
      provides a tool for testing this possibility. METHOD OF STUDY: Phytohemagglutinin
      stimulated lymphocytes were incubated for 48 hr in the presence of culture media
      from in vitro fertilized eggs, as well as in follicular fluid (FF) and control
      supernatants. Total RNA was isolated from the lymphocytes by the guanidine
      isothiocyanate method and interleukin (IL)-10 mRNA expression was detected by
      reverse transcription-polymerase chain reaction. RESULTS: Ten percent of the
      activated lymphocytes incubated with FF expressed IL-10 mRNA, whereas 88% of the
      lymphocytes activated with supernatants of sperm + oocytes gave a positive
      signal. Significantly (P < 0.05) fewer (50%) lymphocytes stimulated in the
      presence of control supernatants also expressed mRNA for IL-10. In supernatants
      of activated lymphocytes incubated with the culture medium of spermia + oocytes,
      the concentration of IL-10 was significantly higher than in the lymphocytes
      incubated with FF. CONCLUSION: These data suggest that the presence of the
      fertilized ovum induces a Th2 shift, which enables pregnancy to proceed to term.

PMID- 9645265
TI  - Supplementation effect of early pregnancy factor-positive serum into bovine in
      vitro fertilization culture medium.
AB  - PROBLEM: Early pregnancy factor (EPF) has been detected in pregnant bovine serum,
      and its activity appeared from 24 to 48 hr after insemination. However, in bovine
      in vitro fertilization (IVF), an EPF-like substance(s) had been detected in the
      culture medium of fertilized ovum. Therefore, we think that EPF and EPF-like
      substance(s) are very important materials for the development of the embryo. In
      this study, we examined the development of the embryo when fertilized bovine ova
      were cultured with IVF culture medium supplemented with EPF-positive or -negative
      serum. METHOD OF STUDY: EPF activity of each serum (fetal calf serum [FCS], calf
      serum [CS], estrus bovine serum, and pregnant bovine serum) was assessed by the
      bovine-rosette inhibition test. The sera were supplemented in TCM-199 culture
      medium, and IVF bovine ova were cultured with the media for 6 or 7 days,
      respectively. The culture media of each group were evaluated for EPF activity by
      the bovine-rosette inhibition test 48 hr after IVF. The cleavage rate of each
      group was calculated at 48 hr, and 6 or 7 days after IVF. The culture medium of
      cumulus cells was also tested for EPF activity. RESULTS: Only the pregnant bovine
      sera were EPF positive. All the culture media 48 hr after IVF became EPF
      positive. Additionally, the culture medium of cumulus cells did not have EPF
      activity. There was no significant difference in the cleavage rate of the EPF
      positive and -negative sera 48 hr after IVF. However, the cleavage rate of EPF
      positive sera tended to be higher than the negative sera. In contrast, the
      blastocyst development rates of EPF-positive sera were significantly higher than
      those of the negative sera 6 to 7 days after IVF (P < 0.05). CONCLUSIONS: The
      data suggest that an EPF-like substance(s) may be secreted from the in vitro
      fertilized bovine ovum but not from the cumulus cell, and that the EPF in the
      pregnant serum may accelerate the development of the bovine embryo in IVF.

PMID- 9645266
TI  - Increased numbers of circulating interferon-gamma- and interleukin-4-secreting
      cells during normal pregnancy.
AB  - PROBLEM: Systemic immune responses during normal pregnancy are suggested to
      deviate toward secretion of T helper (Th)2-like cytokines. METHOD OF STUDY: Blood
      samples from 11 healthy primigravidae in their first, second, and third
      trimesters, and 8 weeks postpartum were examined. Peripheral blood mononuclear
      cells were separated and the numbers of interferon (IFN)-gamma- and interleukin
      (IL)-4-secreting cells were identified by using the enzyme-linked immunospot
      test. RESULTS: In all three trimesters of pregnancy, and also postpartum, the
      numbers of IFN-gamma- and IL-4-secreting cells were significantly higher compared
      with nonpregnant controls (Mann-Whitney; P < 0.001). The numbers of IFN-gamma-
      and IL-4-secreting cells gradually increased as the pregnancy progressed compared
      with postpartum (Kruskas-Wallis; P < 0.01 and P < 0.05, for IFN-gamma and IL-4,
      respectively). The ratios of IFN-gamma/IL-4 during pregnancy and postpartum were
      unchanged, and also when compared with nonpregnant controls. CONCLUSION: The
      results indicate a systemic up-regulation of both Th1- and Th2-like immune
      responses during normal pregnancy.

PMID- 9645267
TI  - Identification of a unique form of p53 in human cord blood associated with the
      development of maternal autoantibodies.
AB  - PROBLEM: The possible link between p53-reactive antibodies in multiparous women
      and exposure to a unique p53 protein during pregnancy was examined. METHOD OF
      STUDY: p53-reactive antibodies were evaluated in sera from nulligravid and
      multiparous women and patients with ovarian cancer by Western immunoblot.
      Furthermore, the presence of p53 protein was assayed in cord blood by enzyme
      linked immunosorbent assay. Cord blood-derived p53 was compared structurally by
      protein fingerprinting and functionally by gel mobility shift assay to other
      isolates of p53. RESULTS: Antibodies reactive with wild-type p53 were observed in
      92% of multiparous women and 42% were reactive with one tumor-derived p53
      protein. p53 protein was detected in 27 of 154 samples of cord blood. Structural
      analysis indicated that the fetal p53 resembled the UL-1 p53. Functionally, the
      fetal and UL-1 protein failed to bind DNA. CONCLUSIONS: Fetal p53 protein seems
      to be distinct from wild-type p53, characterized by enhanced stability,
      structural differences and inability to bind DNA, analogous to alternatively
      spliced variants. Exposure to fetal p53 protein may form the basis for
      immunologic protection against cancer induced by multiparity.

PMID- 9645268
TI  - Plasma interleukin-12 is elevated in patients with preeclampsia.
AB  - PROBLEM: Abnormal immune activation has been suggested as a contributor to the
      development of preeclampsia. We hypothesized that intact interleukin (IL)-12
      directly, or through its main mediator, interferon (IFN)-gamma, contributes to
      the altered immune response observed in preeclampsia. METHOD OF STUDY: Plasma
      samples were collected from 20 patients with preeclampsia and 20 normotensive
      patients with uncomplicated pregnancies who were matched with the preeclamptic
      patients by age, gestational age, and parity. Samples were collected before the
      onset of labor, induction, or medical intervention. The samples were assayed for
      IL-12 and IFN-gamma by specific enzyme-linked immunoassays. RESULTS: IL-12 was
      detected in 35% of the preeclamptic patients and in 5% of the patients with
      normal pregnancies (P < 0.01). The detection rate and mean concentration of IFN
      gamma were comparable in both groups. CONCLUSION: Intact plasma IL-12 is detected
      more frequently in preeclamptic patients, suggesting the involvement of this
      cytokine in the enhanced immune response observed in preeclampsia.

PMID- 9645269
TI  - Neutralizing antibodies and complement-mediated, antibody-dependent enhancement
      (C'-ADE) of human immunodeficiency virus infection in its vertical transmission.
AB  - PROBLEM: Mother-to-child transmission is a major route for the spread of human
      immunodeficiency virus (HIV) worldwide. Our understanding of its mechanisms and
      parameters is still limited. Among the factors possibly involved in virus passage
      determination are the level and quality of antiviral humoral response. METHOD OF
      STUDY: Anti-HIV-1/Lai neutralizing activity in sera from 35 mother-infant pairs
      (in which 13 transmission cases occurred) was investigated, as was the complement
      mediated antibody-dependent enhancement capacity of the same sera. RESULTS:
      Neutralization titers of 640 or more were found only in four mothers of
      uninfected children, but this result was not significant. No significant link was
      obtained with the occurrence of complement-mediated, antibody-dependent
      enhancement. CONCLUSIONS: As suggested by a synthesis of the literature, vertical
      transmission of HIV is probably the result of multiple active and/or stochastic
      parameters in the mother, the fetal structures, and the viral population. The
      precise definition of cellular mechanisms involved in in utero infection would
      help to better define which immune activity in the mother should be more
      carefully considered.

PMID- 9645270
TI  - Gonadotropins induce the release of interleukin-1 beta, interleukin-6 and tumor
      necrosis factor-alpha from the human preovulatory follicle.
AB  - PROBLEM: The effects of exogenous gonadotropin administration and steroid levels
      on the release of various cytokines into the human follicular fluid (FF) were
      studied. METHOD OF STUDY: Forty patients were included in two groups, those
      undergoing controlled ovarian hyperstimulation (COH) (n = 33) and natural cycles
      (n = 7). FF transvaginal aspirations were performed 36 hr after administration of
      human chorionic gonadotropin or a spontaneous surge of luteinizing hormone,
      respectively. FF cytokine measurements were performed with sensitive
      immunoassays. RESULTS: FF cytokine levels were higher after COH [interleukin (IL)
      1 beta, 6.6 +/- 0.32 pg/ml; IL-6, 18.7 +/- 2.1 pg/ml; and tumor necrosis factor
      (TNF)-alpha, 32.5 +/- 4.9 pg/ml] than in natural unstimulated cycles (0.52 +/-
      0.1 pg/ml, P < 0.001; 8.9 +/- 1.2 pg/ml, P < 0.01; and 13.2 +/- 2.6 pg/ml, P <
      0.001, respectively). FF estradiol (E2) and progesterone levels were not
      statistically different between groups, despite the higher serum E2 levels
      observed in patients after COH. CONCLUSIONS: Gonadotropins might regulate ovarian
      secretion of cytokines, because FF IL-1 beta, IL-6, and TNF-alpha levels after
      COH were higher than during natural cycles.

PMID- 9645271
TI  - A rational basis for the use of combined heparin/aspirin and IVIG immunotherapy
      in the treatment of recurrent IVF failure associated with antiphospholipid
      antibodies.
AB  - PROBLEMS: 1) Does the administration of heparin and aspirin (H/A) in combination
      with intravenous immunoglobulin G (IVIG) improve in vitro fertilization (IVF)
      implantation and birth rates in patients with recurrent IVF failure? 2) Is the
      effect of such treatment related to the antiphospholipid antibody (APA) status of
      the patients concerned? METHOD OF STUDY: Subjects consisted of 89 women younger
      than 36 years of age whose infertility was a result of causes other than male
      infertility and who had experienced four or more failed IVF/embryo transfer
      procedures. Fifty-two women were APA+ (group A), and 37 were APA- (group B). All
      patients, regardless of their APA status, received H/A (5000 U sq bid), aspirin
      (81 mg po qd) from the inception of menotropin therapy along with IVIG (20 g)
      through a single infusion 3 to 10 days before egg retrieval. RESULTS: Twenty-two
      (42%) of group A and 7 (19%) of group B patients achieved live births (P =
      0.020). CONCLUSIONS: IVF outcome is significantly improved when H/A and IVIG are
      administered to APA+ women with repeat IVF failures. APA- women do not seem to
      benefit from such treatment.

PMID- 9645272
TI  - Regain of fertility and normality of progeny born during below protective
      threshold antibody titers in women immunized with the HSD-hCG vaccine.
AB  - PROBLEM: Phase II clinical trials with the heterospecies dimer of beta hCG and
      alpha-subunit of ovine luteinizing hormone (HSD)-human chorionic gonadotrophin
      (hCG) vaccine showed that pregnancy was prevented at and above 50 ng/ml titers,
      whereas conceptions occurred below 35 ng/ml of hCG bioneutralization capacity.
      The effect of below-protective threshold anti-hCG antibodies on the progression
      of pregnancy and the normality of progeny was studied. METHOD OF STUDY: Four
      women enrolled by informed consent in the Phase II trials. The women studied were
      immunized with the HCG vaccine and did not receive booster injections in
      consideration of their desire to have another child. They were examined
      clinically at least once every month until delivery. The babies were followed up
      from 2 to 3.5 years, and their anthropometric indices were compared with elder
      siblings. RESULTS: The pregnancies progressed to 35 to 38 weeks with the usual
      obstetric problems, and the children developed normally. CONCLUSIONS: The anti
      fertility effect of the HSD-hCG vaccine is reversible and low titers of
      antibodies below the protective threshold have no apparent side effects on the
      progression of pregnancy and on the early development of the progeny.

PMID- 9645274
TI  - [Problems and tendencies in monitoring].

PMID- 9645273
TI  - Immunodetection of cell adhesion molecules in rat Sertoli cell cultures.
AB  - PROBLEM: The presence of cell adhesion molecules (CAMs) in Sertoli cells has not
      been explored extensively. The expression of CAMs involved in cell-matrix and
      cell-to-cell interactions in Sertoli cell cultures was examined. METHOD OF STUDY:
      Immunohistochemical and Western blot techniques were applied to rat Sertoli cell
      cultures using specific antibodies to alpha 3, alpha 5, and alpha 6 integrin
      subunits; NCAM; and cadherins. RESULTS: Expression of alpha 3 and alpha 6
      integrin subunits (mainly laminin receptors) and lack of expression of alpha 5
      integrin subunit (fibronectin receptor) was observed in Sertoli cells by
      immunohistochemistry. These cells also expressed neural CAM (NCAM) and N
      cadherin. By Western blot analysis, Sertoli cell extracts reacted with antibodies
      to alpha 3 integrin subunit revealed a band approximately 130 kDa, whereas no
      expression of alpha 5 integrin subunit was detected. Cell extracts incubated with
      antibodies to pan cadherin exhibited a band approximately 120 kDa, whereas bands
      of 180, 140, and 120 kDa were observed with antibodies to NCAM. CONCLUSION: New
      data about the expression of receptors for extracellular matrix proteins (alpha 3
      and alpha 6 integrin subunits) as well as cell-to-cell adhesion molecules (NCAM
      and cadherins) are reported in rat Sertoli cell cultures.

PMID- 9645275
TI  - [Monitoring in anesthesiologic practice].
AB  - Monitoring has made great strides in the last half century. It enables us to
      titrate drugs to the desired effect, warns us of impending danger, and helps with
      the diagnosis of problems confronting our patients. Beyond that it has enormously
      increased our understanding of anesthetic pathophysiology. Modern monitors,
      however, are still focused on single variables; they do not provide the panoramic
      view offered by our senses. They do not give data on the patient's appearance,
      movement, or position. The clinician incorporates that type of information with
      the data provided by the monitors and melds that with a much richer information
      about the system in which the operates, the colleagues with whom he works and the
      circumstances that affect his patient. Even though we appreciate the importance
      of that wealth of information, we lack scientific tools to measure its value.

PMID- 9645276
TI  - [Preoperative ECG in routine preoperative assessment of children].
AB  - OBJECTIVE: The aim of this study is to examine whether a routine preoperative ECG
      is necessary in children to assess the risks in anaesthesia and surgery. METHODS:
      We examined the records of 3030 children anaesthetized in our hospital in 1990
      and compared records of complications with preoperative ECGs. We also evaluated
      questionnaires on this subject which we had sent to 51 large pediatric hospitals
      in Germany in 1991. RESULTS: During 3030 anaesthetic procedures there were 93
      complications, 67 of which were not of cardiac origin. Of the 26 cardiac
      complications only 4 needed therapy (AV-Block 2 degrees, fall in blood pressure).
      Preoperative ECGs were recorded in 180 cases: 152 were normal, 8 showed harmless
      deviations from normal and 16 were recorded because of known cardiac defects.
      None of the 180 children developed complications during anaesthesia. Our
      questionnaire was returned completed carefully by 36 of the 51 hospitals. In most
      hospitals a preoperative ECG is only recorded when heart disease is known or
      suspected. CONCLUSION: Routine preoperative ECGs are unnecessary in children
      unless there are clinical symptoms of heart diseases or heart disease is
      suspected.

PMID- 9645277
TI  - [Cytokine release and changes in mononuclear cells in peripheral blood under the
      influence of general anesthesia].
AB  - OBJECTIVE: Anaesthetic agents are believed to have an adverse effect on human
      immune defense mechanisms. We investigated changes in peripheral immune cell
      numbers such as natural killer (NK) cells, B cells and T lymphocyte
      subpopulations (CD4+ and CD8+ cells) and differences in cytokine production after
      stimulation with different mitogens before and during narcosis. METHODS: We
      studied 30 patients undergoing elective orthopedic surgery. Stimulatory
      experiments were performed with the mitogens lipopolysaccharide (LPS),
      phytohemagglutinin (PHA) and inactivated Newcastle Disease Virus (NDV). RESULTS:
      During general anaesthesia with fentanyl, thiopental, isoflurane and nitrous
      oxide there was a significant decrease of circulating NK cells in the peripheral
      blood accompanied by a significant increase of B cells and CD8+ T lymphocytes. We
      detected a significant anesthesia-associated increase of interferon (IFN)-gamma,
      INF-alpha, tumor necrosis factor (TNF)-alpha and soluble interleukin-2 receptor
      (sIL-2R) synthesis after stimulation with different mitogens while interleukin
      (IL)-1 beta and IL-6 protein did not change significantly. After the beginning of
      surgery CD8-positive cells showed a return to control values and NK cell number
      increased slightly. CONCLUSION: These findings suggest that general anaesthesia
      interferes with immune cell number and immune cell response. This may explain the
      clinically well-recognized disturbance of human immunity after surgery and
      general anaesthesia.

PMID- 9645278
TI  - [Are tramadol enantiomers for postoperative pain therapy better suited than the
      racemate? A randomized, placebo- and morphine-controlled double blind study].
AB  - The goal of this prospective, randomised and double-blind pilot-study was to
      investigate the analgesic potency and the side-effects of tramadol enantiomers in
      clinical practice. One hundred patients recovering from orthopaedic surgery with
      a postoperative pain intensity of more than 50 on a visual analogue scale 0-100
      mm (Table 1) were recruited for the study. They were treated in a randomised,
      double-blind way with a maximal dose of 150 mg i.v.(+)-,(-)-tramadol, racemate,
      or 15 mg i.v. morphine or saline in the placebo group (5 groups, 20 patients
      each). The primary criterium of efficacy was the number of responders defined as
      patients with a pain reduction of at least 20 on VAS after 40 min. In case of
      pain, responders were allowed to continue with the double-blind drug up to six
      hours. The non-responders were treated with morphine as the rescue analgesic. The
      secondary criterium was the incidence and severity of side-effects. Six patients
      terminated the study prematurely. One patient was excluded because of an allergic
      reaction to morphine, one patient could not be treated sufficiently with
      morphine, four were excluded because of protocol violations. There were 8
      responders in the (+)-tramadol-,6 in the (-)-tramadol- and 6 in the racemate
      group, 16* (P < 0.05) in the morphine group, and 5 in the placebo group. Pain
      intensity after 40 min was reduced by 20 (p < 0.05), 17 (p < 0.05), 17 (p <
      0.05), 36 (p < 0.01 vs placebo, p < 0.05 vs (+)-,(-)-tramadol, and racemate
      group) and 5 mm on the VAS in the (+)-, (-)-, (+/-)-tramadol-, morphine- and
      placebo-group, respectively. Thirty eight adverse events like nausea, vomiting,
      PCO2-increase, and urinary retention occurred in 20 patients, most frequently in
      the (+)-tramadol- and morphine group. Sedation was significantly less profound in
      the (-)-tramadol group 1-4 h postoperatively. There were no side-effect in the
      tramadol racemate group. The enantiomers were equal to the racemate in analgesic
      potency, but inferior by far to morphine. They showed more adverse events and,
      hence, can not be preferred to the racemate in postoperative pain therapy.

PMID- 9645279
TI  - [Is there a means for cost reduction in intensive care fluid therapy without a
      loss of quality?].
AB  - Cost reduction in fluid therapy may be possible without a loss in quality of
      medical therapy if the following principles are adhered to. 1: Compare the prices
      of different manufacturers. 2: The greater the product unit, the cheaper the
      milliliter. Adherence to this principle is limited by hygienic and logistic
      considerations. 3: 0.9% NaCl-solution is cheaper than Ringer's lactate-solution.
      Lactated Ringer's solution should be used, only, if there are contraindications
      against the higher solute concentrations and tonicity of 0.9% NaCl. 4:
      Crystalloids are cheaper than colloids. When choosing between these two options
      intravasal duration of action and specific adverse events must be considered. 5:
      Cost reduction by differential indication of artificial colloids. Comparing
      prices, one must consider risk of anaphylactoid/anaphylactic reactions, duration
      of action, limitation of dosage and possible hemostasis disorders. 6: Restrictive
      use of albumin. Albumin is the most expensive colloid. There are no reasons for
      routine use.

PMID- 9645280
TI  - [Preclinical blood gas analysis. 1. The value of preclinical blood gas analysis].
AB  - Prehospital blood gas analysis is a new method in out-of-hospital emergency care.
      In a prospective pilot study we evaluated the feasibility of prehospital
      compensation of severe acidosis relying on different monitoring systems to
      evaluate patients oxygen, carbon dioxide or acid-base status, respectively.
      METHODS: With the help of arterial blood gas checks taken at the site of the
      emergency, the acid base status of patients undergoing out of hospital
      cardiopulmonary resuscitation was analysed. The values derived from the first
      arterial puncture were used to determine the presence and the type of acidosis.
      The data of the arterial blood gas checks were set into relation with the time
      elapsed since the beginning of resuscitation and they were compared with end
      tidal CO2. RESULTS: During the observation period 26 blood gas analyses from
      patients who had out-of-hospital resuscitation because of cardiac arrest were
      done. Twenty three patients had severe acidosis (pH range < 6.9 to 7.31), one had
      alkalosis (pH 7.51). Only two had an arterial pH within normal range. The pCO2
      was variable (range: 24 to 97 mm Hg). The correlation of pH with time from the
      beginning of resuscitation to arterial puncture was poor (r = 0.407, p < 0.05).
      There was no correlation between pH and BE (r = 0.267) or pH and pCO2, (r =
      0.016) respectively. Prehospital capnometry had a poor correlation with arterial
      pCO2 in most emergency patients. Only patients with respiratory disturbances of
      extrapulmonary origin showed a good correlation between end-tidal CO2 and the
      arterial pCO2. In severely ill patients the arterio-alveolar CO2-difference was
      unexpectedly high (> 15 mm Hg). In four patients resuscitation was not successful
      until compensation of an unexpectedly severe acidosis based upon the findings
      from blood-gas analysis had been performed. CONCLUSIONS: Arterial blood gas
      analysis proved to be helpful in the optimal management of out of hospital
      cardiac arrest. The incidence of severe acidosis in patients undergoing
      cardiopulmonary resuscitation was 80%. The probability of developing acidosis was
      found to increase slightly depending on the time elapsed since the beginning of
      CPR. The application of a calculated buffering of acidosis with sodium
      bicarbonate showed a good outcome in selected cases. In emergency patients
      alternative methods fail to detect severe disturbances of the patients oxygen
      and/or carbon dioxide status and the acid-base balance. Management of prehospital
      cardiac arrest could be optimized by the routine use of blood gas analysis.

PMID- 9645281
TI  - Validating of a transoesophageal ultrasonic-Doppler-probe to the detection of air
      in the venous blood.
AB  - OBJECTIVES: The aim of this study was to compare the sensitivity of a newly
      applied transoesophageal ultrasonic Doppler sensor for detection of air with the
      traditional precordial ultrasonic Doppler sensor in clinical use. METHODS: We
      studied 16 patients undergoing neurosurgical procedures in a sitting position.
      Two ultrasonic Doppler devices were compared as to their ability to detect venous
      air embolisms (VAE): transoesophageal (ODM II, co. Abbott) versus a precordial
      ultrasonic Doppler sensor (Parks Medical Electronics Inc.). After establishing
      general anaesthesia and endotracheal intubation, we applied an ultrasonic Doppler
      sensor to the right sternal border of the patient's chest and inserted an
      ultrasonic Doppler probe into the oesophagus. With the patient in the sitting
      position, microparticularly d-galactose was injected to verify the efficacy of
      both ultrasonic Doppler devices. RESULTS: Using ODM II by positioning the probe
      toward the azygos vein, a dosage of 1 ml microparticularly d-galactose was
      detected in every patient. When adjusting the ODM II-probe on the right
      myocardial wall or using the precordial ultrasonic Doppler sensor, the
      administration of microparticularly d-galactose was detected by the devices in
      only 11 patients. CONCLUSIONS: This study demonstrates that a transoesophageal
      ultrasonic Doppler sensor (ODM II) is more efficient than the precordial
      ultrasonic Doppler sensor for monitoring patients who are at risk of VAE by
      sonification of the azygos vein.

PMID- 9645282
TI  - [New results in the visualization of the spinal dura mater with scanning electron
      microscopy].
AB  - Although there are various published descriptions of the dura mater spinalis [4,
      7, 9, 11, 16], some points relating to the texture of the collagen fibres in the
      dura have still not been adequately explained. In this study the orientation of
      the collagen fibril bundles was revealed with the aid of scanning electron
      microscopy, and our observations have yielded new insights into the three
      dimensional structure of the human dura mater spinalis. MATERIALS AND METHODS:
      The preparations used were taken from the bodies of four persons who had died of
      acute cardiac infarct at the ages of 70-78 years. The histories of these patients
      gave no indications of earlier neurological, endocrine or septic illnesses. The
      tissue examined was taken 8-12 h after death in all cases; it was immediately
      fixed in glutaraldehyde and then processed for scanning electron microscopy in
      the usual way. RESULTS: In the outermost (epidural) layer of the dura mater
      spinalis the collagen fibres are bunched together in bands that run in all
      directions. Elastic fibres 2 mm thick are woven into this three-dimensional
      network of collagen systems. On the inside (the arachnoid side) thin collagen
      fibres are fused into layers in such a way that the innermost layer resting on
      the arachnoid has a smooth, shiny appearance comparable to that of a serosa. It
      is attached to the actual dura with a supporting band of connective tissue. Rests
      of the subdural neuroepithelium could contribute to the smooth appearance of the
      superficial aspect. CONCLUSIONS: The outermost layer of the dura is made up
      mainly of collagen fibres, which run in all three directions--longitudinal,
      horizontal and transverse--both singly and in groups. These findings are at odds
      with "classic" descriptions, according to which the fibres in the dura mater
      spinalis all have a parallel course with a longitudinal orientation in tangential
      sections.

PMID- 9645283
TI  - [Polytrauma. Preclinical early support and shock management].

PMID- 9645284
TI  - [Small-volume resuscitation in hypovolemic shock. Remarks on the work of U.
      Kreimeier et al. Anaesthesist (1997) 46:309-328].

PMID- 9645285
TI  - [Syringe- or lead change for TCI?].

PMID- 9645286
TI  - [Post-spinal headache].

PMID- 9645287
TI  - [A medium of the third kind: sensible use of the internet in anesthesia].

PMID- 9645288
TI  - [Arterial hypertension: its impact on perioperative morbidity and mortality].
AB  - Chronic hypertension is associated with structural as well as functional changes
      of the vasculature, in particular of the coronary, cerebral and renal
      circulation. It is important to realise that [1] functional changes are often the
      result of structural changes, [2] the longer lasting the hypertension, the slower
      and less complete the regression of structural changes, and [3] acute
      "normalisation" of arterial pressure in long-standing hypertension may initially
      induce functionally subnormal smooth muscle and/or cardiac activity because the
      structure of the cardiovascular system is adapted to function at elevated
      pressures. Despite a multitude of studies, the impact of hypertension on peri
      operative morbidity and mortality remains controversial. There are as many
      studies seeming to suggest that preoperative hypertension correlates with adverse
      outcome as there are studies that fail to establish such a relationship. When
      looking at the combined evidence, one is inclined to conclude that hypertension
      is a predictor of "soft" outcomes (e.g. peri-operative myocardial ischaemia and
      transient post-operative neurologic deficit) rather than an independent predictor
      of "hard" outcomes (e.g. unstable angina, myocardial infarction and cardiac
      death). In view of lack of convincing outcome data, it is impossible to recommend
      a generally acceptable management strategy for the hypertensive patient.
      Although, in general, a gradual reduction of blood pressure over a period of
      weeks to months is the optimal therapeutic approach, we will be hard-pressed
      delaying surgery for the sole purpose of "better blood pressure control". With
      full appreciation and detailed knowledge of the pathophysiology of hypertension,
      combined with sophisticated haemodynamic monitoring and interventions in the peri
      operative period, acutely anaesthetising an inadequately treated hypertensive
      patient will probably not adversely affect his outcome. Delaying surgery for
      additional work-up may possibly improve outcome in patients with target organ
      disease, evidence of secondary hypertension, in the most severe forms of
      hypertension or sudden-onset hypertension.

PMID- 9645289
TI  - [Measurement of the humidity of inspired air in ventilated patients with various
      humidifer systems].
AB  - INTRODUCTION: Humidification of inspired gas in artificially ventilated patients
      positively influences mucociliary function and secretolysis. We performed this
      study to examine the properties of heat and moisture exchangers in comparison
      with hot water humidifiers and dry artificial ventilation. METHODS: We measured
      inspired humidity with a special sensor in 41 patients after coronary artery
      bypass grafting with cardiopulmonary bypass. Three Heat and Moisture Exchangers
      (HME) and a hot water humidifier were used to humidity the inspired gas of
      artificially ventilated patients. Humidity measurements were compared. RESULTS:
      Hot water humidifiers produced the highest humidification (average of 38.4 mg/l,
      37-43 mg/l); lowest humidification was produced by dry artificial ventilation
      (average of 8.7 mg/l, 6-11 mg/l). Heat and moisture exchangers (HME) produced
      humidity between 24 and 36 mg/l. Highest humidification was produced by HME
      hygrobac s (average of 32.2 mg/l, 31-36 mg/l) and hygrovent s (average of 31.4
      mg/l, 29-35 mg/l); lowest humidification was produced by HME hygroster (average
      of 28.6 mg/l, 24-31 mg/l). Multifactorial analysis shows a significant impact of
      the humidification method on the humidity of inspired gas. The multiple
      comparison procedure (Tukey) shows significant differences (alpha = 0.05) between
      all humidification techniques on inspired gas except the heat and moisture
      exchangers hygrobac s and hygrovent s. CONCLUSIONS: Hygrobac s and hygrovent s
      may be an alternative to hot water humidifiers. Further clinical studies of HMEs
      and hot water humidifiers will be necessary to evaluate the influence of inspired
      gas humidity on the outcome of artificially ventilated patients.

PMID- 9645290
TI  - [Early and long-term results of percutaneous dilatation tracheostomy (PDT
      Ciaglia) in 195 intensive care patients].
AB  - PURPOSE: Tracheostomy is frequently required in the treatment of critically ill
      patients to prevent the complications associated with prolonged translaryngeal
      intubation. Tracheostomy may facilitate airway suctioning and improve patient
      comfort in the process of weaning. The purpose of the study was to assess our
      experience with PDT and to evaluate the complications in comparison with open
      surgical tracheostomy which is associated with complication rates ranging up to
      50%. METHODS: PDT was performed using the serial dilational technique described
      by Ciaglia (percutaneous tracheostomy introducer set, Cook Critical Care) by
      careful fibreoptic monitoring of the tracheal puncture and the tracheostomy tube
      insertion. Complications related to the procedure and late effects were recorded.
      RESULTS: 195 PDT were performed in adult intensive-care patients on prolonged
      mechanical ventilation. In 182 cases (93.4%) placement of the tube was successful
      without complications. Intraoperative complications occurred in 13 patients
      (6.6%) including bleeding (5), superficial lesion of the tracheal mucosa (3),
      pneumothorax (1) and others (4). After decannulation in 132 patients the
      tracheostoma closed spontaneously and the cosmetic and functional results were
      good. In 131 cases there was no clinical, radiographic and endoscopic evidence of
      symptomatic tracheal stenosis. Only in one patient 6 weeks after decannulation a
      relevant stenosis was seen. In 72 patients after median sternotomy no stomal
      wound infection and no mediastinitis was observed. CONCLUSIONS: PDT is a safe and
      practicable alternative technique which can be performed in the intensive-care
      unit with a lower risk of complications than open surgical tracheostomy.
      Endoscopic guidance prevents serious complications and apparently increases the
      safety of this procedure.

PMID- 9645291
TI  - [Desflurane versus isoflurane in geriatric patients. A comparison of psychomotor
      and postoperative well-being following abdominal surgical procedures].
AB  - PURPOSE: The new volatile anaesthetic agent desflurane has a significantly lower
      blood-gas partition coefficient (0.42) than isoflurane (1.4), suggesting
      excellent intraoperative control of anaesthesia and rapid emergence and recovery
      from anaesthesia. However, only limited experience is available in geriatric
      patients undergoing major abdominal surgery. METHODS: After approval by the local
      ethics committee and with written informed consent, 52 patients (> or = 65 years
      old, ASA class II or III) scheduled for major abdominal surgery were randomised
      to receive either desflurane (DES) or isoflurane (ISO) for maintenance of
      anaesthesia. After oral premedication with midazolam 3.75-7.5 mg, anaesthesia was
      induced with etomidate 0.2-0.3 mg/kg and fentanyl 3 micrograms/kg. Vecuronium 0.1
      mg/kg provided muscle relaxation for endotracheal intubation. All patients were
      mechanically ventilated to maintain normocapnia. For maintenance of anaesthesia,
      DES or ISO was administered in 60% N2O and additional boluses of fentanyl and
      vecuronium were given as required. At the end of surgery, the neuromuscular
      blockade was reversed with neostigmine 0.02 mg/kg and DES or ISO was discontinued
      at the end of skin closure. Episodes of bradycardia and tachycardia and hypo- and
      hypertension, the time from the end of anaesthesia to extubation, opening eyes,
      squeezing hand, stating name and birthdate and to discharge from the recovery
      room were recorded. Until 360 minutes after the end of anaesthesia, the recovery
      of psychomotor functions was measured by means of simple reaction time tests,
      critical flicker fusion test, labyrinth test, ball bearing test, short and long
      term memory test and digit symbol substitution test. The patient's well-being was
      documented with scores for pain, sedation and postoperative nausea and vomiting.
      RESULTS: Demographic data in both groups was similar (Tab. 1). Anaesthesia was
      significantly prolonged in the ISO group. No significant differences between
      groups were found for MAC hours and the total dose of fentanyl and vecuronium
      administered (Tab. 3). Intraoperative haemodynamics were comparable between both
      groups (Tab. 4). No episodes of increases in heart rate or blood pressure
      associated with rapid increases in DES concentration were seen. Early emergence
      parameters were faster in the DES group (Tab. 5). When compared to ISO, the
      overall test performance and testing ability was superior following DES.
      Psychomotor tests showed significantly better results up to 240 minutes after the
      end of DES anaesthesia (Tab. 7, Fig. 4). Comparing the postoperative well-being,
      there were mild advantages for DES (Tab. 6, Fig. 1, 2, 3). However, time to
      discharge of geriatric patients from the recovery room was significantly shorter
      in the DES group (median 171 vs. 215 min., p < 0.05). CONCLUSION: Using a
      balanced anaesthesia technique, we found desflurane as suitable as isoflurane for
      geriatric patients. Additionally, due to the fast emergence from anaesthesia, an
      improved cooperativity was found. In the DES group overall better postoperative
      psychomotor performance resulted in a shortening of discharge times from the
      recovery room. Hence, desflurane anaesthesia may be advantageous in geriatric
      patients.

PMID- 9645292
TI  - [Therapy with blood and blood components. 2. Perioperative management of
      hemostatic disturbances with blood components].

PMID- 9645293
TI  - [Early extubation following intracranial procedures: pro].

PMID- 9645294
TI  - [Early extubation following intracranial procedures: contra].

PMID- 9645295
TI  - [Effect of starvation on the ultrastructure of hepatocytes of Hemidactylus
      frenatus (Lacertilia: Gekkonidae) with special emphasis on peroxisomes].
AB  - The influence of starvation on hepatocyte ultrastructure of Hemidactylus frenatus
      (Lacertilia: Gekkonidae) was investigated with special emphasis on peroxisomes.
      Wall lizards (Hemidactylus frenatus) were sacrificed after different periods of
      starvation and their livers were processed for standard transmission electron
      microscopy. Peroxisomes were demonstrated by means of the 3,3'-diaminobenzidine
      (DAB) cytochemical technique. A control group consisted of individuals which were
      fed "ad libitum" with Tenebrio molitor larvae. After a 7-day period of starvation
      the ultrastructural observation of hepatocytes disclosed a marked reduction of
      glycogen and lipid inclusions associated with fragmentation of the endoplasmic
      reticulum (ER). In later stages of starvation (14 and 25 days) ER proliferation
      and partial reconstruction of glycogen aggregations were observed. Increasing
      numbers of peroxisomes were arranged either in clusters (14 days) or in close
      association with mitochondria, lipid droplets and elongated crystalloid
      structures (25 days). Particularly noteworthy is the increasing cytochemical
      response of these organelles to the DAB reaction, suggesting greater metabolic
      activity of catalase. These data suggest that morphological and functional
      plasticity of hepatocytes may contribute to adaptation of Hemidactylus frenatus
      to prolonged starvation.

PMID- 9645296
TI  - [Genesis and importance so-called inflammatory infiltration of the placenta. II.
      Immunohistochemical findings].
AB  - We investigated the morphologically distinct forms of inflammatory infiltration
      of the placenta both histologically and immunohistologically (n = 24). Our
      material included cases of membraneous inflammation (chorioamnionitis),
      inflammatory infiltration of arteries in the chorionic membrane, basal and
      intervillous placentitis. NACE staining was used to detect myeloid cells and
      monoclonal antibodies (LCA, CD3, CD8, CD20, CD68). To detect lymphoid and
      macrophageal cells we also measured the proliferation activity with MiB 1. In
      cases of chorioamnionitis and subchorial demarcation and in the arteries of the
      chorionic membranes the main inflammatory cell is the myeloid cell (most often
      the mature neutrophil granulocyte). T-lymphocytes were only occasionally found.
      In cases of intervillous placentitis, on the other hand, lymphocytic infiltration
      predominates, consisting of T-lymphocytes which are mostly CD8 negative, and some
      monocytes and macrophages. Basal inflammation in the demarcation zone was
      characterized by T-lymphocytes. We interpret this as indicating basal
      demarcation. According to our histological and immunohistological observations,
      "asphyxial infiltrates" are abortive forms of a placental (bacteriological)
      inflammation, possibly infective in origin. We do not consider asphyxial
      infiltration to be a separate entity with its own causal pathogenesis.

PMID- 9645297
TI  - Dentition and dentigerous bones in juveniles and adults of Polypterus senegalus
      (Cladistia, Actinopterygii).
AB  - Tooth types, their arrangement and the mode of tooth replacement were studied in
      juvenile and adult specimens of Polypterus senegalus by means of scanning
      electron microscopy of cleared and stained specimens as well as sections. All the
      dermal bones of the oropharynx are almost completely covered with teeth except
      for the angulare. The same is true for the branchial apparatus where only the
      hyoid skeleton is toothless. The teeth are uniformly monocuspid and conical, but
      can be classified according to shape and size into three types. These types and
      the mode of tooth replacement are characteristic for each dermal bone. In some of
      the jaw bones each tooth possesses a lingually situated replacement tooth. This
      is true for the teeth of the premaxillary, the maxillary, and the dentary which
      are arranged in a single line, and those of the dermopalatine, the coronoids, and
      the vomer which are in several lines and graded in size. Replacement teeth of all
      the other dentigerous elements develop on top of existing pulpal openings,
      forming an anastomosing common pulpal complex only after resorption of the
      previous tooth. The tooth plates of the dermal bones of the branchial apparatus
      are connected by syndesmosis only to the perichondrally ossified and to the
      cartilaginous or connective tissue material of the elements of the gill-arches.
      The dentition and its association with the bones of the head in Polypterus
      senegalus bear resemblances to advanced actinopterygians on the one hand (e.g.
      differentiation of tooth-types, arrangement), but also some similarities to
      living Amphibia (anchoring material and mode of replacement) on the other. The
      accentuation of a single marginal line of large teeth in both, the outer and the
      inner dental arcade of the jaws is a peculiarity of Polypterus that in a way
      parallels the derived state of similar monolinear tooth arrangements in
      Actinopterygii and Tetrapoda.

PMID- 9645298
TI  - The electron microscopic morphology of the common carotid artery in rats.
AB  - The common carotid arteries of normal adult rats were investigated electron
      microscopically after tannic acid fixation. This fixation technique yields a
      better demonstrability of the structures of the connective tissue, the basal
      laminae and the surface coat of the cell membrane. The common carotid artery
      represents a vessel of the elastic type. The intima consists of an endothelium
      and a narrow gap of connective tissue (0.1-1 micron) which contains single
      collagenous fibrils and small elastic structures. This space is only occasionally
      as wide as 3 microns, especially beneath gaps of the internal elastic membrane.
      In these areas, single cells and structures of densely packed filaments are
      additionally observed which can neither be attributed to collagenous fibrils nor
      to elastic fibres. The intima is demarcated from the outside by an internal
      elastic membrane (1 micron) which shows a number of gaps. The media exhibits 3 to
      4 elastic membranes without gaps. Smooth muscle cells of the contractile type
      stretch in an oblique direction between these membranes, i.e. they are not
      arranged in a circular or spiral manner. Most of their process-rich ends are
      inserted directly into the elastic material and not via a basal lamina. Processes
      from these smooth muscle cells, collagenous fibrils and elastic fibres are seen
      in the intercellular spaces. The muscle cells are occasionally interlinked by gap
      junctions. The basal lamina does not surround the muscle cells continuously. The
      adventitia contains bundles of collagenous fibrils, fibrocytes, a few small
      vessels and nerves with a perineuronal envelope. Nerves could not be demonstrated
      in the media. The oblique course of the smooth muscle cells and the insertion
      into the elastic membranes indicate that these cells do not predominantly
      contribute to changes in the width of the lumen but also serve the stabilisation
      and resetting of the elastic membranes. Contraction is probably induced by an
      opening of stretch-dependent Ca2+ channels. Due to the interlinkage with gap
      junctions, the muscle cells of one layer respond as a functional unit. Our
      findings provide a morphological basis for elucidating commonly encountered
      changes, such as smooth muscle migration through a normally interrupted inner
      elastic lamina.

PMID- 9645299
TI  - The structure of the skin of the tree frog (Hyla arborea arborea L.).
AB  - The aim of the study was to investigate the structure of the skin of the adult
      tree frog Hyla arborea arborea L. by scanning electron microscopy (SEM) and light
      microscopy (LM). SEM observation shows that the skin from the dorsal part of body
      is smooth whereas the ventral part has regular ridges and grooves. The
      superficial layer of the skin consists of irregular shaped epidermal cells
      covered with microridges differing on the dorsal and ventral skin. Two types of
      gland outlets, funnel-type and collar-type, are seen on the surface of the
      epithelium. The dorsal and ventral skin observed in LM contained three kinds of
      glands: mucous glands, and two different types of serous glands, type I and II.
      The mucous glands are small and located in the upper layer of the stratum
      spongiosum of the connective tissue. The serous glands are large. Type I glands
      with small secretory granules (1-3 microns) appear sporadically in both the
      dorsal and ventral skin. Type II glands with large secretory granules (5-15
      microns) are very numerous, particularly in the dorsal skin. Many capillaries
      invaginate to the epidermis of the ventral skin facilitating absorption of water
      in these sites. The lipid glands occurring in the skin of phyllomedusine frogs
      are not observed in the skin of the tree frog.

PMID- 9645300
TI  - Two types of three-dimensional structures formed by epithelial cell aggregates
      from the rat ventral prostate in collagen gel culture. The amount of activated
      charcoal for absorbing serum.
AB  - Cells taken from the rat ventral prostate and cultured formed a tubular structure
      inside the collagen gel in a medium containing activated charcoal-absorbed serum
      after a 14-day incubation. This might suggest that the active substances of serum
      could induce isolated epithelial cells to form such a spherical or tubular
      structure, depending on the amount of activated charcoal used for the absorption
      of serum.

PMID- 9645301
TI  - Effects of a combined thermochemotherapy on the xenotransplanted human mammary
      carcinoma MX-1. A light and transmission electron microscopic study.
AB  - A thermochemotherapy (TCT), consisting of the administration of the alkylating
      agent ifosfamide combined with whole body hyperthermia at 41 degrees C for one
      hour applied to the xenotransplanted human mammary carcinoma MX-1, leads to a
      complete remission within one week. This light and transmission electron
      microscopical study concentrates upon the mechanisms of cell death and upon
      therapy-induced changes in vasculature. These showed that TCT produces necrotic
      rather than apoptotic cell death in xenotransplanted MX-1 tumors, whereas
      apoptosis of endothelial cells was often found. We therefore conclude from our
      experiments that TCT is a very powerful stimulus which directly impels MX-1 cells
      towards coagulative necrosis, while endothelial cells, being probably more
      resistant, often die by apoptosis.

PMID- 9645302
TI  - Morphology and development of the postdiaphragmatic part of the sympathetic trunk
      in the pig (Sus scrofa L.) during its prenatal period.
AB  - The experiment was conducted on 36 swine fetuses divided into the three
      developmental groups described by Marrable (1971). In the postdiaphragmatic part,
      10 to 20 primary ganglia were found in the sympathetic trunk. They had fused with
      the secondary structures, and hence the sympathetic trunks studied finally
      consisted of 6-16 ganglia. It is remarkable that the higher number of primary
      ganglia did not correspond with the higher number of secondary ones. The
      variation in the number of secondary ganglia was mainly connected with the
      interganglionic fusion occurring in the section studied. The standard variation
      in the length of the sympathetic ganglia increased considerably with the age of
      the fetuses as well as the analogous coefficient of variation. The analysis of
      the statistical parameters referring to the ganglia of the investigated section
      of the sympathetic trunk investigated indicated the growth of its developmental
      dynamics, which did not occur until the terminal period of gestation.

PMID- 9645303
TI  - A quantitative assessment of the jugular foramen.
AB  - While it is generally accepted that the right jugular foramen is larger than the
      left, little quantitative evidence exists on the exocranial and endocranial
      openings of this foramen. The present study set out to clarify and quantify
      measurements of the two openings. The dimensions of the exocranial and
      endocranial openings of the jugular foramen and the volume and height of the
      jugular fossa were examined in a total sample of 93 skulls from white and black,
      male and female South Africans. The volume of the jugular fossa was determined
      with the use of a dental impression material. The exocranial area of the right
      jugular foramen was significantly larger (p < 0.05) than the left in the black
      group, while the endocranial area of the right foramen was significantly larger
      (p < 0.05) than the left only in black males. The height of the jugular fossa was
      significantly larger (p < 0.05) on the right side only in the black group. The
      volume of the jugular foramen was significantly larger (p < 0.05) on the right
      side only in females of both groups. Although the jugular foramen is generally
      larger on the right side than on the left, its size as well as the volume and
      height of the jugular fossa is variable in different groups and sexes.

PMID- 9645304
TI  - [Topographic and anatomic study of lateral upper arm transplants].
AB  - An anatomic and topographic study of the lateral upper arm free flap for the
      clinical use in reconstruction. Defects of the laryngopharynx and the oral cavity
      after cancer ablation are increasingly reconstructed by free microvascular
      anastomosed tissue transfer. Besides the jejunum transplant we use the free
      radial forearm flap frequently. This flap is suitable for restoring intraoral and
      pharyngeal integrity. Major disadvantages are the requirement of a skin graft to
      obtain wound closure and the cosmetic deformity. The lateral upper arm free flap
      is intended as alternative method for the fasciocutaneus tissue transfer. Based
      on our dissection of ten cadavers we demonstrate the anatomy of the flap, the
      harvesting technique, and present data of vascular pedicle length, vessel
      calibers, and flap size. The vessel calibers of the profound brachial artery (X =
      2.5 mm) and its terminal branch, the posterior radial collateral artery (X = 1.8
      mm), are comparable to the radial artery. The pedicle length can be extended up
      to 13 cm by using a lateral approach. The subcutaneous tissue volume was 1.3 cm
      in average, and compared to the radial flap rather thick. Because of his bulky
      and strong fascia the lateral arm flap seems to be useful as a fascia-fat flap in
      facial augmentation or as a fascia flap in soft tissue reconstruction.
      Disadvantageous are the difficult dissection technique and the loss of
      sensitivity on the lateral aspect of the forearm. Where a fasciocutaneous flap is
      indicated, we prefer the radial forearm flap.

PMID- 9645305
TI  - [Neurovascular infrahyoidal myofascial flap. Anatomic and topographic study of
      the innervation and blood supply].
AB  - The neurovascular infrahyoidal myofascial flap: An anatomical and topographical
      study of the innervation and blood supply. 15 cadavers had bilaterally been
      examined for the topography of the upper thyroid artery and vein and of the lower
      cervical ansa, as an axial bundle of vessels and nerves for the infrahyoidal
      myofascial flap. With the injection of methylene blue the vascular territories of
      the upper thyroid artery had been demonstrated. The upper thyroid artery and vein
      could be found in all cases. This artery was deriving in 47% from the external
      carotid artery, in 30% from the bifurcation and in 23% from the common carotid
      artery. The vein flowed in 43% into the facial vein and in 37% into the internal
      jugular vein. In the remaining 20% several segmental veins were found, which
      flowed into the jugular vein separately. In case of a far caudally situated
      vascular bundle the radius of rotation can be limited in cranial direction. The
      voluntary innervation of the muscles of this flap is derived from the lower
      cervical ansa. The upper radix of the ansa can be found 1 cm in latero-cranial
      direction of the greater horn of the hyoid bone, where it is separating from the
      hypoglossal nerve. The upper thyroid artery is supplying the infrahyoidal
      musculature in the whole extension from the hyoid bone to the sternum. Therefore
      it is possible to develop a myofascial flap of 3.5 cm x 11.5 cm in size, which is
      pedicled at an upper vascular and nerval bundle. Depending on the radius of
      rotation defects of the floor of mouth, of the tongue and of the oro- and
      hypopharynx can well be covered with this new neurovascular myofascial flap.

PMID- 9645306
TI  - Neuronal pathways from foot pad afferents to hindlimb motoneurons in the low
      spinalized cats.
AB  - Experiments were performed on 16 adult spinalized (L2) cats. Postsynaptic
      potentials (PSPs) produced by electrical stimulation of afferent nerves
      innervating foot pads were recorded from hindlimb motoneurons innervating the
      following hindlimb muscles: the posterior biceps and semitendinosus (PBSt),
      anterior biceps and semimembranosus (ABSm), lateral gastrocnemius and soleus
      (LGS), medial gastrocnemius (MG), plantaris (P1), tibialis anterior (TA),
      popliteus (Pop), flexor digitorum longus and flexor hallucis longus (FDHL) and
      peroneus longus (Per.l). The rate of occurrence of different types of PSPs
      (EPSPs, IPSPs and mixed PSPs), the size of the PSPs and their central latencies
      were analyzed for each group of motoneurons to identify the neural pathways from
      the afferents innervating foot pads to hindlimb motoneurons. The rates of
      occurrence of different types of PSPs did not depend on the foot pad stimulated
      in PBSt, ABSm and LGS motoneurons, but for other groups of motoneurons their
      rates of occurrence depended on the foot pad stimulated. It was often noted that
      the size of PSPs in the same motoneurons differed according to the foot pad
      stimulated. Measurements of the central latencies of the PSPs indicated that the
      shortest neural pathways for EPSPs and IPSPs were disynaptic (central latencies <
      1.8 ms). The functional role of neuronal pathways from afferent nerves
      innervating foot pads to hindlimb motoneurons could be to maintain stability of
      the foot during different postural and motor activities.

PMID- 9645307
TI  - Lipid peroxidation and phospholipid composition in rat brain regions after
      ischemia and in early perfusion periods.
AB  - Lipid peroxidation products (LPPs) and phospholipid composition were studied in a
      model of four-vessel occlusion in rats in homogenates of cortex, striatum and
      hippocampus after 30 min forebrain ischemia and following 1, 5, 10, 15, 30 and
      180 min of recirculation. Major modification of LPPs was found after shorter
      reperfusion time, 5 min in hippocampus and 15 min in cortex and striatum when
      compared to control, while a slight decrease in the level of LPPs in the striatum
      and hippocampus was detected after longer (30 and 180 min) intervals. However,
      significant decrease was found in the homogenates of cortex. The results obtained
      from enhanced iron-dependent peroxidation in homogenates of frontal and occipital
      cortex indicated marked susceptibility to lipid peroxidation in the tissue
      subjected to 30 min ischemia and after 15 min of recirculation. The level of DG +
      PA was significantly higher during ischemia in the striatum, while increased
      hydrolysis of PI and DG + PA concentrations in the cortex, PI and PE levels in
      the striatum and PE and PS in the hippocampus after 30 min of ischemia were
      found. After 15 min of reperfusion considerably higher degradation of almost all
      phospholipids was found within all brain regions studied. The irreversibility of
      changes in PS, PE and SM was noted in the hippocampus after longer reperfusion
      periods. Our results indicate that the correlation between the lipid peroxidat
      ion product formation and phospholipid hydrolysis does exist, and, moreover,
      early reperfusion period seems to be highly critical in the development of
      ischemia-reperfusion induced neuronal damage.

PMID- 9645308
TI  - Cervical and cerebellar projections of lamina VII and VIII neurones of the S2
      segment in the cat's spinal cord.
AB  - Dual projections to the sixth cervical segment and to the cerebellum were
      electrophysiologically investigated in neurones from the second sacral segment of
      the spinal cord in cats under chloralose anaesthesia. 49 neurones were
      antidromically identified following stimulation of the ipsilateral and
      contralateral spinal gray matter of the C6 segment and the contralateral inferior
      cerebellar peduncle (coRB), 28 of the total sample projected to the C6
      bilaterally, 17 contralaterally and 4 ipsilaterally. 24 neurones of bilateral or
      contralateral projection to the C6 could be additionally activated from the coRB.
      The cells were distributed in Rexed's laminae VII and VIII with neurones
      projecting to the cerebellum located more medially. Conduction velocities of
      axons ascending in lateral funiculi were comprised in the range 42-96 m/s and the
      decrease was observed in some cases when compared distal and proximal parts of
      axons. No differences were found when compared values for neurones with or
      without cerebellar projection. It is suggested that both propriospinal and
      supraspinal projections of the investigated neurones take part in hindlimb
      forelimb coordination.

PMID- 9645309
TI  - Relation between fibre composition and daily duration of spontaneous activity in
      ankle muscles of the cat.
AB  - This study concerns the relation between use and fibre type composition among
      limb muscles. The histochemical properties were investigated for ankle muscles
      from cats that had previously been studied in 24 hr electromyographic (EMG)
      recordings of daily spontaneous activity. We then reported average daily "duty
      times" (i.e. the percentage of total sampling time filled with EMG activity) of
      1.9% for extensor digitorum longus (EDL), 2.1 and 4.0% for anterior and posterior
      sites of tibialis anterior (TA), 6.6 and 9.5% for anterior and posterior sites of
      peroneus longus (PL), and 13.9% for soleus (SOL). In the present experiments,
      muscles from which these data had been obtained were sectioned in a cryostat and
      stained for myofibrillar ATPase. Fibres were classified as type I (presumably
      slow) or II (presumably fast), the latter fibres being further categorized as
      IIA, IIB and a minor portion of transitional IIAB fibres. As expected, SOL was
      100% type I. Among the muscles of mixed fibre-type composition ("mixed muscles"),
      a statistically significant difference in the mean percentages of type I fibres
      was found between TA or EDL (2.9-6.0%) vs. PL (11.8-14.6%). For TA the percentage
      of type I fibres was higher in posterior (deep) than in anterior (superficial)
      sampling regions; for PL no clear antero-posterior difference was found. A
      significant correlation was obtained between the percentage of type I fibres and
      the total duration of daily activity recorded from corresponding mixed muscle
      sites (5 different recording sites in 4 cats, totally 15 cases of successfully
      combined physiological and histochemical measurements, r = 0.76, P < 0.001).
      Similarly, within TA the total duration of daily activity was higher for sites
      with high (posteriorly) than for those with low (anteriorly) percentages of type
      I fibres. IN CONCLUSION: a "coarse-grain" relationship was found between fibre
      type composition and the duration of daily activity among mixed muscles. Possible
      mechanisms underlying this relationship are discussed.

PMID- 9645310
TI  - Microinjections into the pedunculopontine tegmentum: effects of the GABAA
      antagonist, bicuculline, on sleep, PGO waves and behavior.
AB  - Neurons in the peribrachial region (PB) at the pontine border are implicated in
      the generation of ponto-geniculo-occipital (PGO) waves, which appear
      spontaneously during rapid eye movement sleep (REM) and in association with
      alerting behaviors during waking, as well as in the regulation of REM itself. It
      has been hypothesized that PGO-related bursting in a subpopulation of these
      neurons results from low threshold spikes triggered by phasic hyperpolarizations
      or by excitatory inputs reaching a steadily hyperpolarized neuron. The
      hyperpolarization necessary for triggering the low threshold spikes may come from
      local GABA neurons or from GABAergic input into PB. To test the hypothesis that
      antagonizing GABA would alter PGO wave generation and/or behavioral state, we
      microinfused, in cats, the GABAA antagonist, bicuculline, locally into PB and
      monitored behavior, behavioral state and PGO waves recorded in the lateral
      geniculate bodies. Bicuculline produced no significant alteration in PGO wave
      activity. In 3 cats, bicuculline produced behaviors ranging from spontaneous
      orienting and startle (4 cats) to flight behaviors (2 cats) and aggressiveness (2
      cats), an effect probably due to diffusion into the central gray region. Thus,
      the results do not support a GABAA-ergic role in PB in the generation of PGO
      waves.

PMID- 9645311
TI  - Excitatory amino acids as neurotransmitters of corticostriatal projections:
      immunocytochemical evidence in the rat.
AB  - The retrograde transport of a tracer has been combined with peroxidase
      immunocytochemistry to verify whether corticostriatal (CS) neurons contain in
      their cell bodies high levels of glutamate (Glu) and aspartate (Asp). Injections
      of WGAapoHRP-Au in the caudate/putamen of adult rats produced retrograde labeling
      of a large number of layer V neurons of wide regions of the ipsilateral cerebral
      cortex; fewer labeled neurons were also found on the contralateral side. In all
      experiments, most CS neurons were seen in the agranular frontal cortex, in both
      the medial and the lateral subdivisions. Moreover, numerous retrogradely labeled
      neurons were observed in the cingulate cortex and in the granular parietal
      cortex, depending on the location of the injection site in the various
      experiments. The majority of CS neurons examined were immunostained using
      antibodies against glutaraldehyde-conjugates of Glu or Asp. Glu immunopositive
      neurons resulted 52-61% of CS neurons. Asp immunopositive neurons ranged between
      53% and 62%. In the cortical tissue where Glu and Asp antisera were visualized
      simultaneously, up to 96% of the CS neurons were immunostained. The latter
      finding indicates that the populations of Glu and Asp immunopositive neurons are
      largely segregated and that virtually all cortical neurons projecting to the
      striatum contain high concentrations of Glu and/or Asp, thus corroborating the
      hypothesis that CS projections use excitatory amino acids as neurotransmitters.

PMID- 9645312
TI  - Inflammation of the bronchi in broiler chickens, associated with barn dust and
      the influence of barn temperature.
AB  - Broiler chickens were raised in separate rooms kept at temperatures of either 27
      C or 16 C from 28 through 39 days of age. At the high temperature mouth breathing
      was recorded, but it was absent at the lower temperature. The number of dust
      particles in the air was greater in the warm rooms. More than 50% of the chickens
      in warm rooms had microscopic lesions in the bronchi of their lungs, whereas
      fewer than 5% of chickens in cold rooms had such lesions. Large dust particles
      were visible in some of the lesions. It was postulated that the increased
      incidence of lung lesions in chickens from warm rooms was due to mouth breathing
      rather than the higher dust levels in the air of these rooms.

PMID- 9645313
TI  - Experimental infection and transmissibility of Mycoplasma synoviae with delayed
      serologic response in chickens.
AB  - Fifteen mycoplasma-free chickens were contact exposed to five chickens that had
      been experimentally infected with one of three different strains (two field
      strains and one laboratory strain) of Mycoplasma synoviae (MS). Culture and
      polymerase chain reaction (PCR) were positive by 3 days postinoculation (PI) in
      the experimentally infected birds. Lateral transmission was found by 7-14 days
      postexposure. Positive serum plate agglutination (SPA) results were detected 3-4
      wk after positive culture and/or PCR in individual birds. By 42 days PI, all the
      birds in the groups exposed to field strain K1858 or K3344 had become infected as
      determined by culture and PCR, whereas only half of the birds in the group
      exposed to laboratory strain WUV1853 had become infected. Because of the
      unanticipated lack of seroconversion to hemagglutination inhibition (HI) and
      enzyme-linked immunosorbent assay (ELISA) in infected chickens, the study was
      extended. Each group was split into two groups of 10 birds each, one of which was
      vaccinated with a live B1/LaSota Newcastle disease (ND) vaccine virus to
      determine if a viral respiratory challenge might incite a stronger antibody
      response to the mycoplasma infection. All the birds were tested for
      seroconversion 14 and 21 days later. Of the birds vaccinated for ND, a slightly
      greater number were MS positive by SPA than the nonvaccinated birds. This effect
      was not present 21 days after vaccination, and there was no significant
      difference in the MS HI results from these groups, suggesting that the viral
      respiratory infection had little direct impact on seroconversion. The virulent
      field strain (K3344) elicited a stronger MS antibody response than the other
      strains. All results from the MS ELISA were negative in all groups through 9 wk.
      Positive results from PCR analysis correlated well with culture results, whereas
      serologic tests did not detect MS infection for several weeks. Monitoring
      programs solely dependent on seroconversion may be inadequate for diagnosis and
      control of mycoplasma infections.

PMID- 9645314
TI  - Inhibition of Eimeria tenella development in vitro mediated by chicken
      macrophages and fibroblasts treated with chicken cell supernatants with IFN-gamma
      activity.
AB  - Pretreatment of chicken macrophages or fibroblasts with supernatants from
      concanavalin A-stimulated spleen cells or from the virus-transformed cell line
      reticuloendotheliovirus as source of interferon gamma (IFN-gamma) slows down
      subsequent sporozoite replication in the cells. To identify the presence of IFN
      gamma, we combined four typical activities of IFN-gamma: inhibition of cytopathic
      effect of vesicular stomatitis virus on IFN-gamma-treated fibroblasts, cytostatic
      activity of IFN-gamma-activated macrophages, induction of major
      histocompatibility complex II antigen expression on IFN-gamma-activated
      fibroblasts and macrophages, and induction of nitrite production in macrophages.
      We have shown that chicken fibroblasts and macrophages possess a microbiostatic
      capacity once they are able to prevent the otherwise unchecked intracellular
      replication of Eimeria tenella following activation with culture supernatants
      identified as containing a strong IFN-gamma activity.

PMID- 9645315
TI  - Efficacy of inactivated H5N2 influenza vaccines against lethal
      A/Chicken/Queretaro/19/95 infection.
AB  - The control and eventual eradication of H5N2 influenza virus from domestic
      poultry in Mexico is dependent on the use of avian influenza (AI) vaccine
      strategies. This study was performed to determine the amount of hemagglutinin
      (HA) antigen required to control the signs of disease from a highly pathogenic
      H5N2 influenza virus (A/Chicken/ Queretaro/19/95) and the amount of antigen
      required to prevent shedding of virus from vaccinated birds. Six commercial
      inactivated water in oil H5N2 vaccines available in Mexico were compared with
      standardized vaccines to assess their efficacy. The amount of HA required to
      prevent the signs of disease from A/Chicken/Queretaro/19/95 influenza virus was
      approximately 0.4 microgram per dose. Each of the six commercially available
      vaccines prevented disease signs, and half of the vaccines significantly reduced
      viral shedding from vaccinated birds. There is a need for standardization of AI
      virus vaccine, and the antigen content should be increased in some of the
      commercially available AI vaccines in Mexico.

PMID- 9645316
TI  - Comparison of Salmonella typhimurium challenge models in chickens.
AB  - Experimental infection of chickens with controlled quantities of Salmonella
      typhimurium is often achieved by administration of a single oral inoculum of live
      bacteria to caged chickens. However, this method is a poor simulation of the
      natural process of S. typhimurium infection in the field, making the practical
      application of results obtained under such conditions tenuous. This experiment
      was designed to evaluate the use of horizontal transmission for the
      challenge/infection of chickens with S. typhimurium with the expectation that it
      may more closely resemble the natural situation and, therefore, the in-field
      physiological response of chickens. Further, the experiment allowed for
      comparison of both the kinetics and magnitude of the mucosal immune response
      following each mode of challenge by exposing the chickens to challenge by placing
      them on litter with S. typhimurium-infected seeder birds. Overall, birds
      challenged via seeded litter exhibited a slower rate of infection and a more
      gradual increase in serum antibody production compared with birds receiving a
      single oral inoculum.

PMID- 9645317
TI  - Differentiating turkey postvaccination isolants of Pasteurella multocida using
      arbitrarily primed polymerase chain reaction.
AB  - The chromosomal DNA of 29 field isolants of Pasteurella multocida from commercial
      turkey farms in Missouri and the avirulent Clemson University (CU) and M-9
      vaccine strains of P. multocida were tested using the arbitrarily primed
      polymerase chain reaction (AP-PCR) in combination with 32P-labeled deoxycytidine
      triphosphate (dCTP) and high-resolution gel electrophoresis. The 29 field
      isolants of P. multocida were isolated from outbreaks of fowl cholera in turkey
      flocks in which vaccination with the CU vaccine had been performed within 2 weeks
      of the isolation, and it was suspected that the outbreak could have been due to
      the use of the live CU vaccine. The results of this study showed that: 1) the use
      of the live CU vaccine can lead to the isolation of the vaccine strain if the
      outbreak occurs within 2 weeks of vaccination; 2) a higher proportion of field
      isolants collected during 1983 and 1984, when the usage of the CU vaccine strain
      was highest on Missouri turkey farms, had PCR-amplified product profiles similar
      or identical to those of the CU vaccine strain compared with the period between
      1987 and 1992, when its use was less; and 3) there was no relationship between
      the PCR-amplified product profiles and the serotype.

PMID- 9645318
TI  - Serotype identification of avian infectious bronchitis virus by RT-PCR of the
      peplomer (S-1) gene.
AB  - The S-1 peplomer gene sequences of 31 strains of avian coronavirus infectious
      bronchitis virus (IBV) from North America, Europe, and Australia were compared to
      identify common and unique regions for possible diagnostic applications. S-1
      sequences that were conserved among serotypes and sequences that were variable
      between serotypes were identified. Based on conserved S-1 gene sequences,
      "general" degenerate oligonucleotide primers were designed that amplified IBV
      genomic RNA by the reverse transcriptase polymerase chain reaction (RT-PCR)
      procedure regardless of serotype. Primers specific for IBV serotypes
      Massachusetts, Connecticut, Arkansas, JMK, Delaware (DE/072/92), and California
      (CA/633/85) were designed from regions of the S-1 gene exhibiting extensive
      sequence hypervariability. The ability to identify these six serotypes of IBV by
      RT-PCR was demonstrated by testing the serotype-specific primers on a panel of
      unknown samples that included 30 reference strains and field isolates previously
      characterized by virus neutralization (VN). The use of serotype-specific primers
      in RT-PCR provides a rapid and accurate means of identifying IBV.

PMID- 9645319
TI  - Cellulitis in broiler chickens: epidemiological trends, meat hygiene, and
      possible human health implications.
AB  - The present work evaluates trends in the incidence of cellulitis during the last
      decade using Canadian National Poultry Condemnation Records. In 1986, only 0.048%
      of the total slaughter broilers were condemned as a result of cellulitis lesions.
      Over the next 10 yr, steady increments in cellulitis condemnations were observed,
      and between 1986 and 1996, the percentage of cellulitis condemnation increased
      11.8-fold. In 1996, more than 2.6 million broilers (0.568% of total slaughter)
      were condemned due to cellulitis; this constituted 30.1% of total condemnations,
      making it the number one condemnation category in 1996. In the context of dynamic
      increase in cellulitis, the problems concerning meat hygiene and possible health
      risk to the consumer are deliberated.

PMID- 9645320
TI  - Latent turkey herpesvirus infection in lymphoid, nervous, and feather tissues of
      chickens.
AB  - In earlier studies, we found that a late gene product, glycoprotein B (gB) was
      highly expressed in lymphoid tissues of chickens inoculated with turkey
      herpesvirus (HVT). The objectives of the present study were twofold. First, we
      wanted to expand on our previous research and determine if gB expression declines
      or disappears during later time periods of HVT infection. Second, we wanted to
      correlate gB expression with presence of HVT, i.e. if gB expression is absent,
      can HVT still be detected? Fifteen 1-day-old chicks were inoculated by
      intraperitoneal inoculation with 2000 plaque forming units of strain FC126 HVT.
      Thymus, spleen, bursa, brachial plexus, sciatic plexus, and feather tips were
      harvested at 21, 28, 35, 70, and 105 days postinoculation (PI). Brachial plexus
      and sciatic plexus were examined at 21, 28, and 35 days PI, and feather tips were
      examined at 21 and 28 days PI. An indirect immunofluorescence assay was used to
      detect HVT gB expression, and an in situ hybridization assay was used to detect
      HVT. At 21 days PI, gB expression was present in the thymus, spleen, and bursa.
      At 28 and 35 days PI, gB expression was detected in the thymus and spleen. At 70
      days PI, gB expression was detected only in the spleen, and at 105 days PI, gB
      expression was not detected in any of the lymphoid tissue (thymus, spleen, or
      bursa). gB expression was not detected in the brachial plexus, sciatic plexus, or
      feather tips at any of the five time points. The bursa contained HVT only at 21
      and 28 days PI. However, HVT was demonstrated in all other tissues from 21 to 105
      days PI. Progression from a productive HVT infection to a latent HVT infection
      results in the loss of gB expression. Throughout this progression, a region of
      the HVT genome can be detected by appropriate methods.

PMID- 9645321
TI  - Pen trial studies on the use of live vaccines to displace virulent Mycoplasma
      gallisepticum in chickens.
AB  - Groups of 10 8-wk-old chickens that had been vaccinated 4 wk previously with the
      F strain, ts-11, or 6/85 strain of Mycoplasma gallisepticum (MG) were challenged
      by placing them in contact with 20 chickens that had been previously infected
      with the virulent R strain of MG. Each month, the 10 oldest chickens were removed
      from each pen and replaced with 10 vaccinated chickens to return the total number
      of chickens in each pen to 30. Chickens were bled and cultured for MG prior to
      contact challenge and at the time of removal from the challenge pen. The strain
      of all MG isolates was determined by rapid amplified polymorphic DNA. All vaccine
      strains were isolated from tracheas prior to contact challenge, but colonization
      by the 6/85 vaccine strain was inconsistent. Beginning with the group placed in
      contact 3 mo after the initiation of the study, F strain had begun to displace
      the R challenge strain. By the eight month, F strain had completely displaced the
      R strain in that pen. However, neither strain ts-11 nor 6/85 was able to displace
      the R strain under the conditions of this study.

PMID- 9645322
TI  - Recombinant chicken interferon-gamma-mediated inhibition of Eimeria tenella
      development in vitro and reduction of oocyst production and body weight loss
      following Eimeria acervulina challenge infection.
AB  - Recombinant chicken interferon-gamma (chIFN-gamma) was produced in CHO-K1 or
      Spodoptera frugiperda (SF9) insect cells by transfection with a pcDNA vector or
      recombinant baculovirus (SF9-interferon-gamma [IFN-gamma] carrying the chIFN
      gamma gene. A rabbit antibody against a synthetic peptide corresponding to an
      immunogenic portion of chIFN-gamma recognized a 22-23-kDa band in SF9-IFN-gamma
      cell extracts by western blot analysis. Biological activity of recombinant chIFN
      gamma was shown by its inhibition of vesicular stomatitis virus-induced
      cytotoxicity of chicken embryonic fibroblast cells in vitro. To investigate the
      role of chIFN-gamma during Eimeria infection, CHCC-OU2 chicken cells either
      pretreated with chIFN-gamma or stably transfected with the chIFN-gamma gene were
      infected with Eimeria tenella sporozoites. IFN-gamma demonstrated significant
      reductions in intracellular sporozoite development without affecting sporozoite
      invasion of host cells. Furthermore, chickens treated with recombinant chIFN
      gamma showed decreased oocyst production and significant improvement in body
      weight gain following Eimeria acervulina challenge infection. These results
      provide the first direct evidence that chIFN-gamma exerts an inhibitory effect
      against Eimeria and provides a rational basis for use of this cytokine as a
      vaccine adjuvant against coccidiosis.

PMID- 9645323
TI  - Airborne transmission of Salmonella enteritidis infection between groups of
      chicks in controlled-environment isolation cabinets.
AB  - Although direct contact with infected birds and indirect contact with
      contaminated environmental surfaces are known to be important factors in the
      dissemination of Salmonella enteritidis in poultry flocks, the potential role of
      airborne transmission is less clearly defined. This study considered the
      mechanism by which S. enteritidis might spread between groups of chicks housed in
      controlled-environment disease transmission cabinets, separated by an unoccupied
      space that prevented any direct or indirect contact. Airflow in these cabinets
      was directed across the unoccupied area from one ("upstream") group of chicks to
      the other ("downstream") group. In each of four replicate trials, two groups of
      25 chicks were placed in the upstream ends of transmission cabinets and orally
      inoculated with S. enteritidis at 1 week of age. One day later, 25 1-day-old
      chicks were placed in the downstream end of each cabinet. When chicks were
      removed and sampled at 3 and 7 days postinoculation, S. enteritidis was found on
      the feathers of 77% of the downstream chicks. Moreover, 33% of the downstream
      chicks became infected with S. interitidis. The comparative frequencies of
      recovery of S. enteritidis from various downstream sampling sites suggested that
      infection was apparently transmitted principally by oral ingestion, perhaps from
      environmental surfaces contaminated by airborne movement of the pathogen.
      Reducing the airborne movement of S. enteritidis in poultry houses should thus
      help limit the spread of infection within flocks and thereby diminish the
      incidence of production of contaminated eggs.

PMID- 9645324
TI  - Genetic heterogeneity in the VP2 gene of infectious bursal disease viruses
      detected in commercially reared chickens.
AB  - The genetic heterogeneity of infectious bursal disease virus (IBDV) vaccine
      strains was compared with IBDV detected in bursa tissue of commercially reared
      chickens. The vaccine strains tested represented classic viruses from the United
      States, South Africa, England, and France plus variant viruses from the United
      States. Bursa tissue samples used for the detection of IBDV from commercially
      reared chickens were from the United States. Genetic heterogeneity was examined
      using restriction fragment length polymorphisms (RFLP) of a 743-bp fragment of
      the VP2 gene that was amplified using reverse transcriptase/polymerase chain
      reaction (RT/PCR). The RT/PCR products were digested using restriction enzymes
      BstNI and MboI. On the basis of RFLP profiles, viruses were placed into molecular
      groups. Thirty-eight vaccine and laboratory strains of IBDV were placed into five
      molecular groups. Groups 1 and 2 contained variant viruses, groups 3 and 4
      contained classic viruses, and group 5 contained Lukert/Edgar strain classic
      viruses. In contrast to these five molecular groups, 22 molecular groups were
      observed for 70 IBDV-positive samples from U.S. chicken flocks. Twenty-two of the
      70 IBDV-positive samples were placed into molecular groups 1 (2 samples), 2 (18
      samples), and 5 (2 samples). Nineteen new RFLP profiles that did not match the
      five molecular groups observed for vaccine strains were detected. No viruses were
      observed to have RFLP profiles like molecular groups 3 and 4 observed in the
      vaccine strains. The genetic heterogeneity was greater among IBDV strains
      circulating in commercially reared poultry compared with vaccine strains of the
      virus.

PMID- 9645326
TI  - Potential for transmission of the finch strain of Mycoplasma gallisepticum
      between house finches and chickens.
AB  - Although Mycoplasma gallisepticum (MG) is established in house finch (Carpodacus
      mexicanus) populations in at least 33 states, the potential risk of MG
      introduction to domestic poultry by infected finches currently is unknown. The
      objectives of this study were to determine if chickens could be infected with the
      finch strain of MG via direct, across-wire, and proximity (across-room) contact
      with naturally infected house finches and to determine if house finches could be
      infected through direct contact with experimentally infected chickens. Chickens
      were infected with the finch strain of MG through direct contact with naturally
      infected house finches, a determined by seroconversion (80%), polymerase chain
      reaction (PCR) (20%), and culture of MG (30%). Clinical disease was not observed
      in infected chickens. Isolates from chickens were identified as the original
      finch strain by arbitrary primed PCR. Transmission required an extended period of
      direct contact (10 wk) with infected finches, and no evidence of MG infection was
      detected in chickens exposed to infected finches across wire or across the room.
      Evidence of contact transmission of MG from infected chickens to house finches
      was limited to positive serum plate agglutination results, and infection could
      not be confirmed by PCR or culture. Results suggest that minimal biosecurity
      measures that restrict direct contact between chickens and house finches should
      significantly reduce the potential for MG transmission between these species.

PMID- 9645325
TI  - Molecular characterization of seven Chinese isolates of infectious bursal disease
      virus: classical, very virulent, and variant strains.
AB  - Seven infectious bursal disease virus (IBDV) strains isolated from China have
      been characterized in this study, including a classical strain CJ801, an
      attenuated strain GZ911, a variant strain GZ902, and four very virulent strains
      G9201, G9302, F9502, and HK46. With the use of reverse transcription-polymerase
      chain reaction, the full-length VP2 genes were amplified and the hypervariable
      regions were sequenced. Protein sequences of the hypervariable region (a.a. 143
      382) of the field isolates confirmed their identities. CJ801 has the highest
      identity to the classical strains STC and 52/70. GZ902 has the highest identity
      to the American variant strains A, E, and GLS, and they share unique amino acid
      residue at positions 249K and 254S, which are not present in standard serotype 1
      strains. Attenuated strain GZ911, like other cell culture-adapted strains, has
      substitutions at positions 279(D to N) and 284 (A to T) as well as in the serine
      rich heptapeptide region. Hence, these substitutions may take an important role
      in the reduced virulence of these strains. The four very virulent strains have
      the highest identity to the European very virulent strain UK661 and Japanese
      strain OKYM. These strains share unique amino acid residues at positions 222A,
      256I, and 294I, which are not present in other less virulent strains. The very
      virulent strains isolated in Guangdong (G9201, G9303) and Fujian (F9502)
      Provinces have one to five amino acid substitutions at the two hydrophilic
      domains of VP2 comparing with UK661 and OKYM, indicating that new very virulent
      strains are evolving. Phylogenetic analysis suggests that Chinese very virulent
      IBDVs and European very virulent strains are derived from similar origin.

PMID- 9645327
TI  - The effect of inoculating Enterococcus faecalis into the yolk sac on chick
      quality and maternal antibody absorption.
AB  - Four hundred thirty-two 1-day-old specific-pathogen-free chicks were randomly
      divided into 36 groups of 12. All chicks were given 0.2 ml of Newcastle disease
      antiserum (hemagglutination-inhibition [HI] titer 1:5120) by injection into the
      yolk sac at hatch. Half of the groups received 0.2 ml of Enterococcus faecalis
      (4.0 x 10(8) colony-forming units/ml) by injection into the yolk sac at hatch
      (treatment). The remaining 18 groups received no bacteria (control). Two
      treatment groups and two control groups were weighed, bled, killed, and yolk sac
      weighed daily for the first 9 days of life. Feed was weighed at placement and at
      the end of the trial. Blood was tested for packed cell volume (PCV), total plasma
      protein, and Newcastle disease HI titer. No significant difference was observed
      between treatment and control groups for chick body weight, PCV, and feed
      consumption. Total plasma protein and retained yolk weight were significantly
      higher for treatment groups over control (P < 0.01 and P < 0.0001, respectively).
      Also, the geometric mean serum HI titer (log2) for Newcastle disease antibody was
      significantly higher in the control chicks vs. the treatment chicks (P < 0.01).

PMID- 9645328
TI  - Infectious bronchitis virus antibodies in tears and their relationship to
      immunity.
AB  - Antibodies to infectious bronchitis virus (IBV) in chicken tears were
      investigated to determine if they could be used as an indicator of protective
      immunity. Antibody production in tears and serum was measured by enzyme-linked
      immunosorbent assay (ELISA) in specific-pathogen-free (SPF) white leghorn and
      broiler chickens vaccinated with a live attenuated vaccine containing the
      Massachusetts (Mass) Connaught strain of IBV. The effect of virulent infectious
      bursal disease virus (IBDV) infection on antibody production in tears was also
      evaluated. Immunity was assessed by challenging the chickens with Mass 41 and
      performing tracheal swabbings 5 days later. In addition, tears were also
      evaluated for virus-neutralizing (VN) antibodies to IBV. Following eyedrop
      vaccination, anti-IBV antibodies were consistently detected by ELISA in tears
      prior to and in higher concentrations than in the sera of SPF white leghorn and
      broiler chickens. Maternal IBV antibodies were present in the tear secretions of
      broiler chickens but in lower concentrations than in sera. Infection of SPF
      chicks with a virulent and immunosuppressive strain of IBDV at 1 day of age
      greatly reduced IBV ELISA antibody production in tears as well as serum compared
      with infection of chickens with IBDV at 14 days of age. IBV ELISA and VN antibody
      levels in tears were not accurate indicators of IBV immunity as determined by
      challenge with Mass 41. High tear IBV antibody titers were observed in some
      chickens determined to be susceptible to IBV challenge and low tear titers were
      detected in some protected chickens. This finding suggests that mechanisms other
      than antibody-mediated immunity in tears are important in viral clearance
      following challenge.

PMID- 9645329
TI  - Detection of avian leukosis virus subgroup J using the polymerase chain reaction.
AB  - A polymerase chain reaction (PCR) assay was developed for the detection of avian
      leukosis virus strain J (ALV-J) in chickens. Primers were based in the E element
      and the 3' terminus of the long terminal repeat of proviral ALV-J. PCR products
      were amplified from genomic DNA extracted from chicken embryo fibroblasts (CEF)
      infected with either strain HPRS-103, the prototype of ALV-J, or field isolates
      of ALV-J obtained from broiler breeder flocks in the United States that exhibited
      myeloid leukosis. The newly developed PCR detected ALV-J in DNA prepared from CEF
      inoculated with ALV-J but not from CEF inoculated with subgroup A, B, C, D, or E.
      The PCR also detected ALV-J in DNA prepared from blood, combs, and toes obtained
      from chickens experimentally infected with ALV-J and in DNA obtained from
      peripheral blood monocytes from naturally infected broiler breeder chickens. The
      PCR described here offers a specific and sensitive alternative to conventional
      virus isolation tests for ALV-J.

PMID- 9645330
TI  - Frequency of isolation of Salmonella from protective foot covers worn in broiler
      houses as compared to drag-swab sampling.
AB  - In this study we tested the hypothesis that the frequency of Salmonella isolation
      from protective foot covers worn in individual broiler production houses would
      compare favorably to isolation rates obtained from conventional drag-swab
      methods. Salmonella was detected with equal frequency from protective foot covers
      and drag-swab assemblies on nine individual broiler farms over three separate
      sampling periods. Salmonella was detected in 13 of a total 27 individual
      samplings by culturing the protective foot covers, whereas positive detections
      occurred in 16 of a total 27 samplings when using the drag-swab method. Of the
      total number of houses identified as positive, these frequencies were unaltered
      when evaluated against the flock status of each farm at the time of sampling.
      Both methods were equally as likely to detect Salmonella when houses were either
      vacant (awaiting the placement of the next flock) or occupied (currently housing
      chickens of any age). In addition to highlighting the development of a potential
      new Salmonella monitoring technique, this study reinforces our current
      understanding regarding the importance of stringent biosecurity practices on
      poultry farms.

PMID- 9645331
TI  - Effect of Poultry Litter Treatment (PLT) on death due to ascites in broilers.
AB  - The purposes of this study were to determine the effect of Poultry Litter
      Treatment (PLT) on levels of litter moisture, litter nitrogen, atmospheric
      ammonia, and death due to ascites. Data were collected from chicks raised in
      containment conditions that resembled commercial settings. The ascites death rate
      (5.9%) in broiler chicks on PLT-treated litter was significantly (chi 2 = 15.5,
      df = 1, P = 0.0001) lower than that (31.5%) in broiler chicks raised on untreated
      litter. Likewise, atmospheric ammonia levels in pens that had been treated with
      PLT were significantly (P < 0.05) lower than those in pens that received no
      treatment. Under the conditions of the present study, litter moisture and litter
      nitrogen levels were not different (P > 0.05) among treatments at any sample
      interval.

PMID- 9645332
TI  - Immunorheophoresis for the diagnosis of infectious bursal disease.
AB  - The immunorheophoresis (IR) technique was used for the detection of infectious
      bursal disease antigen from bursae collected from field cases and experimentally
      infected chickens. When these results were compared with that of the agar gel
      immunodiffusion (AGID) test, they showed excellent agreement as determined by
      kappa value. However, the time taken for the appearance of the precipitin lines
      was reduced from 14-24 hr in the AGID test to 3-5 hr in the IR technique.

PMID- 9645333
TI  - Serologic incidence of some diseases in Kansas wild turkeys.
AB  - Wild turkeys (Meleagris gallopavo, n = 1164) were tested for Mycoplasma
      gallisepticum, Mycoplasma meleagridis, Mycoplasma synoviae, and Salmonella
      pullorum from 1990 to 1997. Although 3.3% of the turkeys were suspect for one or
      more diseases, only 0.9% were serologically positive for M. gallisepticum. These
      11 positives were all from one country in south-central Kansas.

PMID- 9645334
TI  - Genetic influence on nitric oxide production during Eimeria tenella infections in
      chickens.
AB  - Studies were carried out to assess the importance of nitric oxide (NO) production
      in vivo in resistance to Eimeria tenella infections through treatment of
      resistant SC and susceptible TK strains of chickens with compounds proven to be
      effective inhibitors of induced nitric oxide synthase. The SC strain produced
      higher levels of plasma NO2- + NO3- in response to primary infection than did the
      TK strain. SC chickens were also more responsive in reduction of NO2- + NO3-
      levels and increased oocyst output in response to treatments with S
      methylisothiourea or NG-methyl-L-arginine (LNMA) during primary infection.
      However, the SC strain, regardless of drug treatment, consistently yielded higher
      oocyst output during primary infection, indicating it could be susceptible to a
      higher parasite burden. On the other hand, the SC strain seemed to develop
      immunity more rapidly than the TK strain, in that oocyst output was decreased in
      both untreated and LNMA-treated chicks upon challenge infection compared with
      that of the TK strain. Oocyst output from both SC and TK strains was further
      decreased by LNMA treatment during challenge infection rather than increased,
      suggesting minimal involvement of NO production in the immune response to
      challenge. These results indicate that NO production during primary E. tenella
      infection may be only one of several immune responses and may not be the main
      anticoccidial effector.

PMID- 9645335
TI  - Eradication of live F strain mycoplasma gallisepticum vaccine using live ts-11 on
      a multiage commercial layer farm.
AB  - Subsequent to use of a live Mycoplasma gallisepticum (MG) vaccination program,
      the F strain of MG had been circulating on a commercial layer farm since 1981. In
      1994, the ts-11 strain was introduced on the farm; each new placement flock was
      vaccinated by eyedrop with ts-11 for one production cycle, and then all
      subsequent placement flocks were left unvaccinated. Birds were monitored by
      culture and serology before and after vaccination. MG isolates were characterized
      by random amplified polymorphic DNA (RAPD). MG was isolated from ts-11-vaccinated
      flocks up to 100 wk of age; all such isolates tested by RAPD were ts-11 type.
      After ts-11 vaccination was discontinued, no MG was detected in nonvaccinated
      birds. After the last vaccinated flock was marketed, no MG was detected on the
      farm. These results indicate a potential use for ts-11 in an MG eradication
      program.

PMID- 9645336
TI  - Axillary cystadenocarcinoma in a Moluccan cockatoo (Cacatua moluccensis).
AB  - An adult Moluccan cockatoo (Cacatua moluccensis) was diagnosed with a
      cystadenocarcinoma in the right axillary region that was treated symptomatically
      with surgical debulking and periodic drainage. The bird eventually died and a
      necropsy was performed. The neoplasm extended through the humerus, and small
      neoplastic foci were seen within the ipsilateral lung parenchyma. Rare groupings
      of microvilli were observed lining intercellular canalicular lumens on electron
      microscopy within the axillary tumor. These findings suggest a respiratory
      neoplasm, although the tissue of origin remained undetermined.

PMID- 9645337
TI  - Pasteurella multocida infection involving cranial air spaces in White Leghorn
      chickens.
AB  - Seven 18-wk-old pullets from a commercial layer flock experiencing increased
      mortality associated with neurologic and respiratory symptoms were submitted to
      the California Veterinary Diagnostic Laboratory System at the Turlock Branch for
      necropsy. Clinical signs included depression, torticollis, swollen eyelids,
      conjunctivitis, and sinusitis. Meningoencephalitis and suppurative inflammation
      of the cranial air spaces were found on histopathology. The brain, sinuses, and
      air spaces of the cranium were infected with Pasteurella multocida. Complicating
      the condition was Mycoplasma gallisepticum infecting the sinus and paramyxovirus
      I affecting the trachea.

PMID- 9645338
TI  - Avian paramyxoviruses serotype 3 isolated from captive birds in Israel: clinical
      signs, pathology, and antigenic characterization.
AB  - Thirteen HA agents were isolated in Israel from captive flamingoes
      (Phoenicopterus ruber), Egyptian geese (Alopochen aegyptiacus) belonging to order
      Anseriformes, and ibis (Guara rubra) belonging to order Ciconiiformes. The
      isolation was done from postmortem materials in three cases of severe respiratory
      disease with high mortality. The isolates were examined serologically and
      identified as belonging to the serotype 3 of avian paramyxoviruses (APMV-3). The
      isolates were more close antigenically to the APMV-3b variety (prototype strain-
      APMV-3/Parakeet/Netherlands/449/75) than to the APMV-3a variety (prototype strain
      -APMV-3/Turkey/Wisconsin/68). This is the first isolation of APMV-3 from birds
      belonging to the orders Anseriformes and Ciconiiformes.

PMID- 9645339
TI  - Intravascular cartilaginous emboli in the spinal cord of turkeys.
AB  - A flock of 15-wk-old tom turkeys experienced an acute onset of paresis and ataxia
      in 75% of the birds after handling. Cartilaginous emboli were found in the spinal
      cord vasculature from one of five turkeys at this initial presentation. Most of
      the flock recovered within 6 days, but 3% remained paretic. Myelomalacia was
      present in three turkeys that failed to recover. Two of these turkeys had
      cartilaginous and osseous emboli within the medullary spaces of the vertebral
      bodies, internal vertebral venous sinuses, and spinal cord. The third turkey had
      vascular and spinal cord necrosis consistent with thrombosis and resultant
      ischemia. These changes suggest that turkeys may be susceptible to a syndrome
      analogous to fibrocartilaginous embolism of the spinal cord in mammals. The
      articular cartilage of the vertebral body endplate may be the source of the
      emboli. The turkeys with emboli had articular cartilage defects consisting of
      matrix eosinophilia, chondrocyte loss, multicellular cluster formation, cartilage
      detachment, and cartilage clefts. Cartilaginous emboli in the spinal cord should
      be considered as a potential cause for acute paresis and ataxia, especially in
      flocks with preexisting abnormalities of the vertebral articular cartilage
      surfaces.

PMID- 9645340
TI  - Correlation between methylation status of the p16/CDKN2 gene and the expression
      of p16 and Rb proteins in primary non-small cell lung cancers.
AB  - In order to clarify the frequency of p16 gene inactivation and its relationship
      with Rb expression, immunohistochemical analysis of p16 and Rb proteins was
      carried out on 82 paraffin-embedded sections of primary non-small cell lung
      cancers (NSCLCs). From immunohistochemical results, abnormal p16 expression was
      observed in 66% of NSCLCs, 80% in squamous cell carcinomas and 46% in
      adenocarcinomas. An inverse correlation between p16 and Rb expressions was noted.
      Moreover, the methylation status of the p16 gene was investigated by the
      methylation-specific polymerase chain reaction (MS-PCR) using 29 frozen samples
      of NSCLCs. MS-PCR revealed the methylation of the p16 gene in 10(34%)of 29
      NSCLCs. All NSCLCs exhibiting methylation exhibited abnormal p16 expression and
      were positive for Rb. In NSCLCs, no difference in methylation status was observed
      with respect to clinico-pathological characteristics including histological
      subtype and tumor stage. Our results demonstrate that abnormality of p16
      expression is frequent in primary NSCLCs and methylation of the promoter of the
      p16 gene occurs in 34% of primary NSCLCs, which might play a significant role in
      the inactivation of the p16 gene.

PMID- 9645341
TI  - Clinical significance of circulating CD44 in non-Hodgkin's lymphoma.
AB  - Soluble isoforms of various adhesion molecules have recently been observed in the
      blood circulation, but the physiological effects of such molecules remain
      unsettled. Our earlier results indicate that soluble CD44 can be detected in sera
      of healthy individuals and that significantly higher levels of serum CD44 (s
      CD44) can be found in lymphoma patients. The serum level of the standard form of
      CD44 parallels the clinical treatment response in patients with lymphoma. In the
      present study, we have investigated the clinical significance of s-CD44 in non
      Hodgkin's lymphoma measured at the time of the diagnosis. S-CD44 was measured
      from the sera of 123 patients with non-Hodgkin's lymphoma by dot blotting high
      levels of s-CD44 were associated with high serum levels of lactate dehydrogenase
      and thymidine kinase, high histological grade of malignancy and poor overall
      survival. However, s-CD44 level did not have independent prognostic value in a
      multivariate analysis. In conclusion, a high s-CD44 level at the time of
      diagnosis was associated with poor survival and several other adverse prognostic
      factors. Our previous and present studies taken together suggest that measurement
      of s-CD44 is a valuable tool to monitor treatment response in lymphoma patients.
      However, it may not be an improved prognostic marker.

PMID- 9645342
TI  - Neuronal src and trk a protooncogene expression in neuroblastomas and patient
      prognosis.
AB  - Neuroblastomas present a wide variety of clinical and biological behaviors, which
      are reflected by the heterogeneous expressions of protooncogenes related to the
      neuronal differentiation and amplification of the N-myc gene. High expression of
      trk A and Ha-ras in neuroblastomas has been shown to be associated with an
      excellent patient outcome. We have previously reported that neuron-specific src
      mRNA was increased in chemically differentiated neuroblastoma cell lines and in
      clinically observed neuroblastomas without N-myc amplification. In the present
      study, to clarify both the value of neuronal c-srcN2 expression as a prognostic
      indicator and the significance of the coexpression of these protooncogenes, we
      examined the expression of 3 alternatively spliced src, trk A and Ha-ras in
      neuroblastoma tissues from 60 patients by competitive RNA-polymerase chain
      reaction (PCR). The results indicate that protooncogene expression in
      neuroblastomas correlated with a favorable outcome for c-srcN2 and trk A. N-myc
      gene was amplified exclusively in tumors with low levels of trk A. Low expression
      of c-srcN2 and trk A might thus characterize different aggressive phenotypes due
      to different signal transduction pathways of neural differentiation in
      neuroblastoma. The combined analyses for c-srcN2 and trk A expression by RNA-PCR
      should provide information about the biological phenotype of a neuroblastoma
      within a short period of time after obtaining tumor material.

PMID- 9645343
TI  - Differential expression of key enzymes of energy metabolism in preneoplastic and
      neoplastic rat liver lesions induced by N-nitrosomorpholine and
      dehydroepiandrosterone.
AB  - Preneoplastic liver foci and neoplasms of different morphological phenotypes were
      induced in rats with N-nitrosomorpholine (NNM; 120 mg/l in drinking water for 7
      weeks) and the peroxisome proliferator dehydroepiandrosterone (DHEA; 0.6% in the
      diet for up to 84 weeks). Preneoplastic glycogen storage foci (GSF) occurred
      mainly upon treatment with NNM, and amphophilic cell foci (APF) were mainly
      observed in rats treated with DHEA alone or in combination with NNM. The 2 types
      of lesions belong to 2 different cellular lineages, the glycogenotic/basophilic
      lineage and the amphophilic lineage, which are characterized by distinct patterns
      of alterations in key enzymes of energy metabolism. Whereas in GSF enzymes of
      glucose metabolizing pathways were modified (increase in glucose-6-phosphate
      dehydrogenase and pyruvate kinase, decrease in glucose-6-phosphatase), APF mainly
      demonstrated alterations in mitochondrial enzymes (increase in cytochrome c
      oxidase, succinate dehydrogenase and glycerol-3-phosphate dehydrogenase) and, to
      a lower extent, in peroxisomal enzymes (increase in peroxisomal hydratase and
      acyl-CoA oxidase). The alterations in enzyme expression reflect an
      insulinomimetic effect in GSF and a thyromimetic effect in APF. Neoplasms
      resulting from APF show a more differentiated phenotype than those arising from
      GSF. We suggest that the different and in many aspects opposite effects of the 2
      carcinogens on key enzymes of distinct pathways of energy metabolism modulate the
      process of neoplastic liver cell transformation and result in phenotypically
      different preneoplasias and neoplasias reflecting different cellular lineages.

PMID- 9645344
TI  - Tissue polypeptide specific antigen in the follow-up of ovarian and cervical
      cancer patients.
AB  - This retrospective study includes 425 serological examinations of 40 patients
      with epithelial ovarian cancer and 356 serological examinations of 33 patients
      with squamous cell cervical cancer. The serum levels of the tumor markers tissue
      polypeptide specific antigen (TPS), carbohydrate antigen 125 (CA 125) and
      squamous cell carcinoma antigen (SCC) were determined. Cutoff values of 93 U/l
      for TPS, 3 microg/l for SCC and 37 U/ml for CA 125 were selected according to the
      95th percentile of serum concentrations measured in healthy control patients. For
      ovarian cancer sensitivity, specificity, positive predictive value (PPV) and
      negative predictive value (NPV) of TPS were 67%, 84%, 59% and 90%, respectively.
      In 27 patients with recurrent ovarian cancer, CA 125 and TPS showed lead time
      effects in 8 and 11 cases, respectively. The combination of CA 125 and TPS
      provided lead time in 14 cases of recurrent disease with a time range from I to
      23 months (median 3.9 months). In cervical cancer, TPS showed a sensitivity,
      specificity, PPV and NPV of 64%, 90%, 85% and 68%, respectively. In 16 patients
      with recurrent cervical cancer, SCC and TPS showed lead time effects in 7 and 8
      cases, respectively. The combination of SCC and TPS provided lead time effects in
      12 cases with a time range from 0.5 to 6 months (median 3.5 months). Our data
      indicate that TPS is a valuable tool in the follow-up of patients with ovarian or
      cervical cancer. However, TPS does not appear to be adequate to replace tumor
      markers CA 125 and SCC.

PMID- 9645345
TI  - Expression of the smooth muscle calponin gene in human osteosarcoma and its
      possible association with prognosis.
AB  - The basic calponin gene is a smooth muscle differentiation-specific gene that
      encodes an actin-binding protein involved in the regulation of smooth muscle
      contractility. We studied the expression of the calponin gene in 8 human
      osteosarcoma cell lines and 17 primary human osteosarcoma tissues by RT-PCR
      analysis. We also analyzed mRNA expression of smooth muscle-specific genes
      including SM22alpha, caldesmon and alpha-actin, and for neutral and acidic
      calponin isoforms. The genes were expressed at various levels by osteosarcoma
      cell lines and tissues of diverse histological subtypes. The basic calponin
      protein of an expected size was detected in osteosarcoma cell lines by immunoblot
      analysis and was localized by immunohistochemistry in the cytoplasm of the tumor
      cells in osteosarcoma tissues. Survival was found to be significantly increased
      in patients whose tumors exhibited basic calponin expression, compared with those
      with no expression. Alterations in the expression of other markers examined were
      not correlated with prognosis. Our results suggest that the basic calponin gene
      product may be a novel prognostic variable in patients with osteosarcoma.

PMID- 9645346
TI  - Expression of hyaluronan in normal and dysplastic bronchial epithelium and in
      squamous cell carcinoma of the lung.
AB  - A series of 85 lung/bronchial tissue samples from 76 patients consisting of
      normal, metaplastic and dysplastic epithelium and different types of lung
      carcinomas were analyzed for the distribution of hyaluronan (HA), using a
      biotinylated hyaluronan binding complex as an HA-specific probe. The normal
      pseudo-stratified columnar bronchial epithelium was either negative for HA or
      displayed a weak staining around the basal cells. The epithelia of serous and
      mucous bronchial glands were HA negative whereas the submucosal connective tissue
      was strongly positive. In metaplastic, dysplastic and carcinoma in situ lesions
      the whole epithelium from basal to uppermost cells expressed HA on plasma
      membranes. Epithelial HA was also found in squamous cell carcinomas, but not in
      adenocarcinomas, carcinoid tumors or small cell carcinomas of the lung. Whereas
      epithelial HA was present in all lesions of the squamous cell type, the staining
      intensity displayed great local variability in 50% of the cases with severe
      dysplasia, carcinoma in situ and squamous cell carcinomas. In squamous cell
      carcinomas, such an irregular staining pattern was significantly associated with
      poor differentiation. Our results indicate that the expression of HA in different
      bronchial lesions and lung tumors is restricted to those showing squamous cell
      differentiation, being absent from other types of lung carcinomas. The increase
      of HA depleted areas in poorly differentiated squamous cell carcinomas emphasizes
      the important role of HA in tumor differentiation. HA on carcinoma cell surface
      may influence tumor growth and metastatic behavior.

PMID- 9645347
TI  - Increased expression of CD44v6 mRNA significantly correlates with distant
      metastasis and poor prognosis in gastric cancer.
AB  - Expression of CD44 and its variants is associated with clinically aggressive
      behavior of some human cancers. The present study was undertaken to determine the
      expression level of these CD44 mRNAs in relation to the clinicopathologic
      features and prognosis of gastric cancer. Using reverse transcription polymerase
      chain reaction followed by Southern blotting, we examined the expression of the
      standard and variant (v6 and v9) forms of CD44 mRNA in 73 cases of gastric
      cancer. We determined the ratio of mRNA expression in cancer tissue to normal
      tissue (T/N ratio) and evaluated the correlations of the ratio with clinico
      pathologic features, tumor progression and prognosis. The expression level of the
      standard form of CD44 (CD44s) mRNA correlated with peritoneal dissemination only,
      and that of CD44v9 mRNA did not significantly correlate with any
      clinicopathologic factor. The expression level of CD44v6 mRNA was significantly
      higher in patients with lymph node metastasis and liver metastasis. In 48
      curatively resected patients, the expression level of CD44v6 mRNA correlated with
      the site of recurrence. Furthermore, there was a significant survival advantage
      in patients with low expression of CD44v6 mRNA compared with those with high
      expression. The level of CD44v6 mRNA expression may be a potential prognostic
      indicator and may be useful as a predictor for distant metastasis and recurrence
      in patients with gastric cancer.

PMID- 9645348
TI  - Clinical relevance of p53 and bcl-2 protein over-expression in laryngeal squamous
      cell carcinoma.
AB  - We investigated immunohistochemically the clinical relevance of the over
      expression of the apoptosis-regulating proteins p53 and bcl-2 in a homogeneous
      series of 149 laryngeal squamous-cell carcinomas. p53 was over-expressed in 75
      cases and bcl-2 in 39 cases. p53 and bcl-2 co-expression was found in 21 cases.
      p53 and bcl-2 immunoreactivity was significantly associated with poor
      histological differentiation and lymph-node metastases. Moreover, a significant
      statistical correlation was found between bcl-2 expression, supraglottic tumor
      site and advanced disease stage. p53/bcl-2 co-expression was significantly
      associated with poor differentiation, tumor extension, the presence of lymph-node
      metastases and advanced clinical stage. Univariate analysis showed that a lower
      probability of survival was significantly associated with supraglottic site,
      tumor extension, advanced clinical stage and p53/bcl-2 co-expression, but not
      with p53 or bcl-2 considered separately. In multivariate analysis, only tumor
      extension and supraglottic site retained their prognostic value. Our data suggest
      that clinical staging remains the most reliable predictive indicator of survival
      in patients with laryngeal carcinoma.

PMID- 9645349
TI  - Prognostic value of loss of heterozygosity and KRAS2 mutations in lung
      adenocarcinoma.
AB  - The prognostic values of loss of heterozygosity (LOH) at loci frequently involved
      in non-small cell lung cancer and of KRAS2 gene mutations were studied in lung
      adenocarcinoma patients. LOHs were relatively common, ranging from 24% at
      chromosome 10p to 55% at chromosome 17p13. KRAS2 mutations at codon 12 were
      present in 26% of cases, were more common in male than in female patients and
      were associated with a smoking habit. No association between LOH at any site and
      clinical stage or survival rate was found. On the other hand, we observed a trend
      between the presence of any type of KRAS2 mutations and poor survival. Analysis
      of specific KRAS2 mutations showed a strong effect of Asp (GAT) and Val (GTT)
      mutations, resulting in a very poor survival compared with wild type group,
      whereas the most common mutation (Cys, TGT) was not associated with prognosis.
      Our results indicate the importance of specific activating mutations of the KRAS2
      gene as genetic markers of clinical outcome for patients with lung
      adenocarcinoma.

PMID- 9645350
TI  - Mutational analysis of Bax and Bcl-2 in childhood acute lymphoblastic leukaemia.
AB  - In childhood acute lymphoblastic leukaemia there are large interpatient
      variations in levels of the apoptosis-regulating proteins Bax and Bcl-2, but the
      molecular basis for this variation is unknown. Point-mutations in bax have been
      reported in cell lines derived from haematological malignancies. Frameshift
      mutations, which result in reduced Bax levels, have also been found in colon
      cancer of the microsatellite mutator phenotype. Bcl-2 overexpression, or gain of
      function mutations in the open reading frame (ORF) or in the translational
      repressor, the upstream ORF(uORF) of bcl-2, might also be important in
      deregulating its function or expression. We have therefore analyzed 21 bone
      marrow aspirates from untreated childhood acute lymphoblastic leukaemia and 2
      from myeloid leukaemia for mutations in box and bcl-2. DNA sequence analysis of
      the ORFs of bax and bcl-2 and of the uORF of bcl-2 revealed no mutations, despite
      the large range in expression levels. Thus, mutations within the (u)ORFs of bax
      and bcl-2 that (in)activate or deregulate Bax and Bcl-2 are infrequent in primary
      childhood acute leukaemia and do not play a major role in regulation of the
      encoded proteins in this disease.

PMID- 9645351
TI  - Impact of menopausal hormone-replacement therapy on clinical and laboratory
      characteristics of breast cancer.
AB  - Hormone-replacement therapy (HRT) is widely used by post-menopausal women.
      Although this treatment may slightly increase the incidence of breast cancer,
      more and more cases are diagnosed while women are taking HRT. The purpose of this
      study was to ascertain the influence of HRT on prognostic factors and outcome of
      breast cancer. Data on all breast-cancer patients, including precise information
      on HRT, was prospectively and systematically recorded in a data base. From 1985
      to 1995, 1379 post-menopausal women fulfilled the eligibility criteria for this
      study. All were treated by us (P.B. and L.P.) in our ward of a large public
      hospital of Marseilles, France. The clinical features, laboratory findings and
      survival rates in 142 HRT users who developed breast cancer while being treated
      were compared with those of 284 matched never user breast-cancer patients.
      Patients who developed breast cancer during HRT had fewer locally advanced
      cancers and smaller and better-differentiated cancers. Lymph-node involvement was
      significantly less frequent in the user group than in the non-user group (non
      significant). Estradiol receptivity was both qualitatively and quantitatively
      lower in users. There was no significant difference with regard to recurrence and
      metastasis-free survival and overall survival. We conclude that HRT does not
      affect the prognosis of breast cancer. Regular surveillance during HRT allows
      early detection of smaller lesions. The higher number of well-differentiated
      cancers and the distribution of hormone receptivity may reflect interaction
      between neoplastic tissue and exogenous hormones.

PMID- 9645352
TI  - Flow cytometric investigation of immune-response-related surface molecules on
      human colorectal cancers.
AB  - Our purpose was to clarify whether human colorectal cancer cells are equipped to
      present tumour-associated-antigens to the immune system, and whether this ability
      correlates with lymphoid infiltration, the Dukes' stage and Jass classification.
      Enzymatically dissociated tumour cells from 70 different colorectal cancers were
      monitored by multiparameter flow cytometry. Gating on EP4+ cells, the expression
      of the surface molecules HLA class I, HLA class II, CD80 (B7-1), CD54 (ICAM-I)
      and CD58 (LFA-3) was evaluated. In 60 of 70 tumours, all tumour cells expressed
      HLA class I, in 10 tumours 15-96% of the tumour cells expressed HLA class I. In 1
      tumour, all tumour cells expressed HLA class II, in 67 tumours some expressed HLA
      class II, in 2 tumours none expressed HLA class II. Expression of CD58 was
      heterogeneous, and there was no or only sparse expression of CD80 and CD54.
      Expression of the HLA class I molecules, but not the class II, was correlated
      with lymphoid infiltration and the Jass classification. Expression of these
      surface molecules was not correlated with the Dukes' stage. The tumour cells were
      generally equipped to present antigens to the effector arm of the immune system
      since HLA class I is expressed, but the tumour cells were not optimal in
      stimulating an immune response, since HLA class II and CD58 were only marginally
      expressed and CD80 and CD54 were absent.

PMID- 9645353
TI  - Detection of colorectal cancer cells in peripheral blood by reverse-transcriptase
      polymerase chain reaction for cytokeratin 20.
AB  - The staging of colorectal cancer currently depends on pathological examination of
      the surgical specimen and regional lymph nodes, accompanied by imaging tests such
      as computed tomography (CT) scanning. However, alternative molecular methods to
      detect circulating tumour cells in blood or bone marrow may provide additional
      information about the extent of disease and prognosis. We have previously
      reported the development of a reverse-transcriptase polymerase chain reaction (RT
      PCR) for cytokeratin 20 (CK 20) mRNA to detect circulating epithelial tumour
      cells. In this study, we report on the application of this method for detecting
      circulating tumour cells in patients with colorectal cancer. Using this method,
      CK 20 mRNA was detected in 8/8 human colorectal cancer cell lines, in 8/9
      biopsies from primary colorectal tumours and in 9/10 biopsies of liver metastasis
      in patients with metastatic colorectal cancer, suggesting that CK 20 may be a
      useful target for the detection of circulating tumour cells in this patient
      group. In spiking experiments, 10 cells were consistently identified in 2 ml of
      whole blood (1 x 10(6)-1 x 10(7) mononuclear cells). In 12/25 (48%) peripheral
      blood samples from patients with known metastatic colorectal cancer, CK 20 mRNA
      was detected. However, there was no correlation between the detection of CK 20
      mRNA in the peripheral blood and disease progression and survival in this group
      of patients. CK 20 mRNA was detected in 1/12 normal blood samples, which raises
      questions about the absolute specificity of CK 20 expression.

PMID- 9645354
TI  - Clinical implications of cyclins, cyclin-dependent kinases, RB and E2F1 in
      squamous-cell lung carcinoma.
AB  - In the search for new risk factors at the molecular and cellular levels, clinical
      data [lymph-node involvement(LN)and stage] were used and 104 squamous-cell lung
      carcinomas were analyzed by immuno-histochemistry for expression of cyclin D1,
      cyclin A, cdk2, cdk4, RB, and E2F1. The results of the univariate analysis of all
      8 factors showed that cyclin A and cdk2 gave the best prognostic information,
      while no prognostic value could be found associated with cyclin D1, cdk4, RB and
      E2F1. The subsequent multivariate analysis of all possible combinations of the
      important factors showed that the pairs LN/cyclin A, LN/cdk2 and cyclin A/cdk2,
      and the triplet LN/cyclin A/cdk2 yielded the best prognostic information. It was
      essentially better than the information given by a single factor.

PMID- 9645355
TI  - Chimeric CD4/CD44 molecules associate with CD44 via the transmembrane region and
      reduce hyaluronan binding in T cell lines.
AB  - Cells of the immune system tightly regulate the binding ability of cell adhesion
      molecules. The binding of the extracellular matrix component hyaluronan to CD44
      is no exception, yet the mechanisms that regulate its binding are poorly
      understood. In this study a chimeric CD4/CD44 molecule, containing the
      extracellular domain of CD4 and the transmembrane and cytoplasmic domains of
      CD44, was expressed in two CD44+ mouse T lymphoma cell lines, BW5147 and T28.
      This resulted in the reduced ability of endogenous CD44 to constitutively bind
      hyaluronan. Immunoprecipitation of the chimeric protein in 1 % Brij-96 indicated
      an association between the chimera and endogenous CD44. Using various chimeric
      CD4/CD44 molecules, the transmembrane region of CD44 was found to mediate this
      association. In addition, the association of chimeric CD4/CD44 molecules with
      endogenous CD44 correlated with reduced hyaluronan binding. Thus, the
      transmembrane region of CD44 is required for the association with CD44 molecules
      in the cell membrane and we propose that the self-association of CD44 molecules
      occurs on the T cell surface to promote hyaluronan binding. Cellular events
      altering the interactions of the transmembrane region of CD44 thus have the
      potential to regulate the hyaluronan binding ability of CD44.

PMID- 9645356
TI  - Two models of murine B lymphopoiesis: a correlation.
AB  - During B cell genesis in mouse bone marrow (BM), precursor B cells pass through a
      series of developmental stages that have been defined by changes in expression of
      various marker molecules. The use of dissimilar phenotypic criteria in different
      laboratories, however, has led to the formulation of disparate models of B
      lymphopoiesis not fully reconciled with one another. We have directly compared
      two such models, one based on expression of intracellular mu heavy chain of IgM
      (c mu) and terminal deoxynucleotidyl transferase (TdT), the other monitoring cell
      surface leukosialin (CD43), heat-stable antigen (HSA; CD24) and the ectopeptidase
      BP-1. Each model uses cell surface B220 glycoprotein (CD45RA) to denote the B
      cell lineage. We have examined the cellular composition of four sorted BM
      fractions by immunofluorescent labeling of CD43, HSA and BP-1, using
      immunofluorescence microscopy of cytocentrifuged fractions to quantitate
      precursor B cell populations expressing either c mu or TdT. The results reveal a
      range of B cell differentiation stages within individual sorted BM fractions,
      providing a cross-reference between these two analytical methods and contributing
      to a unified model of B cell development in mouse BM.

PMID- 9645357
TI  - Failure of P strain mice to respond to vaccination against schistosomiasis
      correlates with impaired production of IL-12 and up-regulation of Th2 cytokines
      that inhibit macrophage activation.
AB  - In contrast to most inbred strains, P mice fail to develop significant resistance
      to Schistosoma mansoni infection as a result of vaccination with either radiation
      attenuated cercariae or schistosome antigens plus Bacillus Calmette Guerin, and
      this failure correlates with defects in macrophage larvicidal activity.
      Supernatant fluids from antigen-treated in vitro cultures of splenocytes from
      vaccinated P mice demonstrate less macrophage stimulatory activity than do
      supernatants from cells of vaccine-responsive strains such as C57BL/6. This is
      not due either to diminished production of the macrophage-activating cytokine IFN
      gamma by P mice, or to a lesser responsiveness of macrophages from P mice to
      activation by IFN-gamma. Rather, P splenocytes produce two-to threefold higher
      amounts of IL-4 and IL-10, cytokines which down-regulate the cytotoxic potential
      of IFN-gamma-treated macrophages. Thus, the macrophage-activating potential of
      cytokine preparations from vaccinated P mice can be completely recovered by in
      vitro treatment with antibodies to IL-4 or IL-10. Moreover, lower levels of IL
      12, a cytokine involved in promoting development of Th1 responses, are produced
      by splenocytes from P mice as compared to C57BL/6 counterparts. These studies
      indicate that a genetic predisposition toward an impaired production of IL-12 and
      an increased production of down-regulatory Th2 cytokines correlate with low
      response to vaccination against S. mansoni.

PMID- 9645358
TI  - Expression of matrix metalloproteinases by human plasma cells and B lymphocytes.
AB  - Matrix metalloproteinases (MMP) are proteolytic enzymes that play a key role in
      tissue remodelling during physiological and pathological processes, by initiating
      the degradation of extracellular matrix. MMP overexpression can lead to tissue
      destruction which is characteristic of chronic inflammatory diseases such as
      rheumatoid arthritis and scleritis. Plasma cells are often abundant at such sites
      of chronic inflammation. In the present study we investigated whether plasma
      cells could contribute to matrix degradation by their expression of MMP In situ
      hybridization and immunohistochemical analyses on diseased synovial and scleral
      tissue demonstrated the expression of stromelysin-1 (MMP-3) and gelatinase B (MMP
      9), but little or no tissue inhibitor of matrix metalloproteinase 1 (TIMP-1)
      mRNA, by IgG-positive plasma cells. Northern blot analysis of RNA extracted from
      a human plasma cell line (ARH-77), Epstein-Barr virus-transformed B cells, and
      purified peripheral blood B cells, demonstrated expression of stromelysin mRNA.
      TIMP-1 mRNA was only detected by the more sensitive reverse transcription PCR
      method in these cell types. Plasma cells and B lymphocytes cultured in the
      presence of monensin demonstrated cytoplasmic gelatinase B. Gelatin and casein
      zymography on conditioned media (CM) derived from cytokine treated plasma cells
      revealed the induction of secreted gelatinase and stromelysin activity. Western
      blotting confirmed the presence of stromelysin-1 and TIMP-1 proteins in plasma
      cell CM. These data suggest that plasma cells are not only capable of modulating
      an inflammatory response by antibody and cytokine production, but also by their
      ability to produce MMP. Secretion of MMP from focal aggregates of plasma cells
      may play a critical role in tissue destructive diseases such as rheumatoid
      synovitis and scleritis.

PMID- 9645359
TI  - Expression of selectin-binding epitopes and cytokines by CD4+ T cells
      repopulating scid mice with colitis.
AB  - Recruitment into the gut of CD4+ T cells and their activation in the colonic
      lamina propria (LP) are key events in the development of colitis in scid mice
      reconstituted with CD4+ T cells from immunocompetent, congenic donor mice. This
      study investigated the expression of cytokines and selectin-binding epitopes by
      CD4+ T cells repopulating different tissues of the adoptive scid host. Cells from
      the inflamed colonic LP of transplanted scid mice produced high amounts of IL-12,
      IFN-gamma and TNF-alpha but only low amounts IL-4 and IL-10. Intracellular
      cytokine staining confirmed the presence of large numbers of IFN-gamma- and TNF
      alpha-producing effector CD4+ T cells in the colonic LP of scid mice with colitis
      but also in non-inflamed tissues [spleen (S), peritoneal cavity (PC) and
      mesenteric lymph nodes (mLN)] of the adoptive host. Cells from these tissues
      furthermore produced large amounts of IL-12. Ligands for endothelial selectins
      are involved in recruiting T cells into inflamed tissues. We have analyzed the
      expression of selectin-binding epitopes on CD4+ T cells repopulating different
      tissues of the adoptive scid host. We found that a large fraction of CD4+ T cells
      from inflamed colonic LP and from non-inflamed PC, mLN and S expressed high
      levels of P- and E-selectin-binding epitopes (P-Lhi) in transplanted scid mice,
      but not in congenic, immunocompetent control mice. Although P-Lhi CD4+ T cells
      were enriched in IFN-gamma-producing subsets from most (but not all) tissues, we
      also found large numbers of in vivo generated P-Llo CD4+ T cells producing pro
      inflammatory cytokines. This was in contrast to in vitro generated Th1 CD4+ T
      blasts that were almost exclusively P-Lhi. In this mouse model, production of Th1
      type pro-inflammatory cytokines and expression of surface epitopes binding
      endothelial selectins are hence strikingly up-regulated in CD4+ T cells residing
      in inflamed and non-inflamed tissues during the development of colitis.

PMID- 9645360
TI  - Mycobacterium tuberculosis exploits the CD95/CD95 ligand system of gammadelta T
      cells to cause apoptosis.
AB  - Vgamma9/Vdelta2+ T cells specifically recognize Mycobacterium tuberculosis in
      vitro and are precociously recruited in early mycobacterial lesions. Even if
      gammadelta T cells are only fortuitously detected in granulomas or
      bronchoalveolar lavages of patients with active pulmonary tuberculosis, a role in
      shaping the mature alphabeta T cell response against M. tuberculosis is
      substantiated. Here we provide a molecular explanation for this paradox: the
      engagement of the gammadelta TCR by mycobacterial antigens induced the expression
      of CD95 ligand (CD95L) by chronically activated CD95+/CD95L- gammadelta T
      lymphocytes. The receptor was functional, as CD95/CD95L interaction triggered the
      bystander death of CD95+ cells by apoptosis. Cell death was abolished by CD95
      blocking antibodies. The transient accumulation at the site of infection of
      CD95L+ gammadelta lymphocytes, capable of interacting with CD95+ leukocytes
      attracted by the response towards the pathogen, may determine the characteristics
      of the ensuing granulomatous disease.

PMID- 9645361
TI  - Attenuated Listeria monocytogenes carrier strains can deliver an HIV-1 gp120 T
      helper epitope to MHC class II-restricted human CD4+ T cells.
AB  - Listeria monocytogenes is a facultative intracellular pathogen which, following
      uptake by macrophages, escapes from the phagosome and replicates in the
      cytoplasm. This property has been exploited using recombinant L. monocytogenes as
      a carrier for the intracytoplasmic expression of antigens when MHC class I
      restricted cytotoxic T lymphocyte responses are required. Much less is known of
      the ability of these bacteria to trigger MHC class II-restricted responses. Here,
      we demonstrate that after ingestion of L. monocytogenes expressing a T helper
      epitope from the gp120 envelope glycoprotein of HIV, human adherent macrophages
      and dendritic cells can process and present the epitope to a specific CD4+ T cell
      line in the context of MHC class II molecules. No significant differences were
      observed when the attenuated strains were trapped in the phagolysosome or
      impaired in the capacity to spread intracellularly or from cell to cell. Similar
      results were obtained using carrier proteins that were either secreted,
      associated with the bacterial surface, or restricted to the bacterial cytoplasm.
      A dominant expression of the TCR Vbeta 22 gene subfamily was observed in specific
      T cell lines generated after stimulation with the recombinant strains or with
      soluble gp120. Our data show that in this in vitro system L. monocytogenes can
      efficiently deliver antigens to the MHC class II pathway, in addition to the well
      established MHC class I pathway. The eukaryotic cell compartment in which the
      antigen is synthesized, and the mode of display seem to play a minor role in the
      overall efficiency of epitope processing and presentation.

PMID- 9645362
TI  - Alpha-1 antitrypsin up-regulates human B cell differentiation selectively into
      IgE- and IgG4- secreting cells.
AB  - Numerous allergens have proteolytic activities. It has been speculated that this
      property may contribute to their allergenicity. Therefore, we have evaluated the
      effect of different physiological protease inhibitors (PI) on the regulation of
      human IgE synthesis. Unexpectedly, the serine PI, alpha-1 antitrypsin, also
      called alpha-1 protease inhibitor (alpha1PI), induced a potent and selective dose
      dependent increase of IgE and IgG4 production by human tonsillar B cells
      stimulated with the IgE and IgG4 switch factors, IL-4 and anti-CD40 mAb. The
      other serine PI tested were inefficient. Furthermore, this effect of alpha1PI was
      accompanied by an increase in (1) germ-line and mature sigma mRNA transcription,
      (2) proliferation and (3) membrane CD23 and CD21 expression, while the expression
      of other molecules involved in the regulation of IgE synthesis was unchanged.
      Since CD23-CD21 pairing plays a crucial role in the up-regulation of IgE
      synthesis, we have tested whether blocking this interaction affected alpha1PI
      increased IgE production. The neutralizing anti-CD23 mAb, Mab 25, partly reversed
      the IgE increase caused by alpha1PI. Moreover, alpha1PI potentiation of IgE
      synthesis was prevented by elastase, a natural substrate of alpha1PI, thereby
      suggesting that alpha1PI may inhibit endogenous B cell enzyme(s) involved in the
      down-regulation of IgE synthesis. Alpha1PI also potentiated IgE and IgG4
      production by IL-4-stimulated peripheral blood mononuclear cells but was not a
      switch factor for IgE and IgG4 as it was unable to replace IL-4 or anti-CD40 mAb
      in inducing IgE and IgG4 production. In conclusion, this study shows that
      alpha1PI acts as a potent co-stimulus for IgE and IgG4 synthesis and suggests
      that the equilibrium between protease/ protease inhibitor participates in the
      control of human IgE and IgG4 synthesis.

PMID- 9645363
TI  - Normal immunoglobulin G protects against experimental allergic encephalomyelitis
      by inducing transferable T cell unresponsiveness to myelin basic protein.
AB  - Normal human IgG for intravenous use (IVIg), administered intraperitoneally,
      protected Lewis rats against experimental allergic encephalomyelitis (EAE)
      induced by immunization with myelin basic protein (MBP). We demonstrate that
      protection was associated with an acquired unresponsiveness of lymphocytes to MBP
      and a decreased ability of the cells to produce IL-2, IFN-gamma and TNF-alpha
      and, to a lesser degree, IL-4 and IL-10, in the presence of the antigen. Lymph
      node (LN) cells of protected rats failed to passively transfer EAE to naive
      syngeneic animals. Our observations indicate that, rather than inducing selective
      immune deviation, IVIg induces preferential MBP unresponsiveness of Th1 cells.
      Whereas LN and splenic cells of IVIg-treated rats did not proliferate nor secrete
      IL-2 in the presence of the antigen, proliferation was restored by adding
      exogeneous recombinant IL-2. In contrast, LN cells of IVIg-treated rats
      proliferated normally and produced IL-2 in the presence of concanavalin A,
      indicating the selectivity for MBP of the anergy induced by IVIg when given at
      the time of immunization with the antigen. Treatment with IVIg also allowed a
      resistance to the secondary induction of EAE, indicating that IVIg protects from
      EAE but does not interfere with the processes that eventually lead to resistance
      to re-challenge. These data document the immunomodulatory effects of IVIg in T
      cell-dependent experimental autoimmune disease and further suggest a role for
      normal Ig in the selection of functional T cell repertoires.

PMID- 9645364
TI  - Immunological memory after somatic transgene immunization is positively affected
      by priming with GM-CSF and does not require bone marrow-derived dendritic cells.
AB  - Inoculation of plasmid DNA is a promising vaccination approach but optimal
      regimes and ways to enhance immunogenicity remain to be established. Among
      natural immunological adjuvants, granulocyte-macrophage colony-stimulating factor
      (GM-CSF) was shown to increase the potency of immunization against tumor cells
      and protein antigens. Here we studied the effect of GM-CSF on memory responses
      against a 12-mer B cell epitope in mice primed with a single DNA inoculation. The
      results show that GM-CSF given at priming as a DNA/GM-CSF chimeric vaccine
      enhances the magnitude of the anamnestic response irrespective of the form of
      antigen used subsequently in the booster immunization. Using mice lacking bone
      marrow-derived dendritic cells we also determined that the enhancing effect is
      not strictly dependent on these cells. These results expand our understanding of
      the activity of GM-CSF in vivo as a modulator of the immune response including
      immunological memory.

PMID- 9645365
TI  - Identification of a human member of the Ly-49 multigene family.
AB  - Three classes of multigene family-encoded receptors enable NK cells to
      discriminate between polymorphic MHC class I molecules: Ly-49 homodimers,
      CD94/NKG2 heterodimers and the killer cell inhibitory receptors (KIR). Of these,
      CD94/NKG2 has been characterized in both rodents and humans. In contrast, Ly-49
      family members have hitherto been found only in rodents, and KIR molecules only
      in the human. In this report, we describe a human cDNA, termed Ly-49L, that
      constitutes the first human member of the Ly-49 multi-gene family. Compared with
      rodent Ly-49 molecules, the Ly-49L sequence contains a premature stop codon and
      predicts a truncated protein that lacks the distal part of a C-terminal lectin
      domain. Evidence is presented that the premature stop codon results from
      incomplete excision of the intron between the first two lectin domain exons.
      Splice variants predicting a full-size Ly-49L protein were not detected. As
      demonstrated by Northern blot analysis, Ly-49L was transcribed by IL-2-activated
      NK cells, but not by freshly isolated B or T cells. PCR screening of a 22-clone
      yeast artificial chromosome contig localized the LY49L locus to the human NK gene
      complex on chromosome 12p12-p13. Southern blot analysis of genomic DNA showed a
      simple pattern with a full-length Ly-49L probe at low stringency hybridization
      conditions, suggesting that Ly-49L may be the only human member of the Ly-49
      multigene family.

PMID- 9645366
TI  - Functional heterogeneity of Thy-1 membrane microdomains in rat basophilic
      leukemia cells.
AB  - Antibody-mediated cross-linking of Thy-1 glycoprotein on the surface of rat mast
      cells and rat basophilic leukemia (RBL) cells initiates biochemical events which
      culminate in secretion of allergy mediators. Thy-1, like some other
      glycosylphosphatidylinositol (GPI)-anchored proteins, forms detergent-insoluble
      complexes containing protein tyrosine kinases (PTK) and some other molecules
      which are implicated in the signaling pathway. On the surface of a rat mast cell
      there are more than 10(6) Thy-1 molecules; however, it is not known which
      fraction of them is involved in transmembrane signaling, and what exactly is the
      heterogeneity of Thy-1 complexes. Using sucrose density gradient
      ultracentrifugation of detergent-lysed RBL cells we found that the density of Thy
      1 complexes depended on the detergent used and the lysis conditions employed.
      Sepharose 4B gel chromatography fractionation followed by density gradient
      ultracentrifugation revealed both size and density heterogeneity of Thy-1 and Lyn
      PTK complexes. Cross-linking of surface Thy-1 caused significant changes in the
      density of these complexes, and an increase in Lyn kinase activity in low/medium
      density fractions. Thy-1 in low-density fractions was relatively resistant to
      cleavage with phosphatidylinositol-specific phospholipase C (PI-PLC).
      Interestingly, removal of only a small fraction of surface Thy-1 by PI-PLC
      abolished the cell activation as determined by tyrosine phosphorylation of
      certain proteins. When Triton X-100 lysates were fractionated at 12000 x g, about
      50 % of Thy-1 remained associated with the nuclear/cytoskeleton pellet; this
      fraction of Thy-1 exhibited an increased sensitivity to PI-PLC. Confocal laser
      scanning microscopy on fixed cells revealed that the total Thy-1 was relatively
      homogeneously distributed over the plasma membrane, whereas the PI-PLC-resistant
      Thy-1 was found mostly in small clusters. The combined data suggest that
      specialized membrane microdomains enriched in Thy-1 with increased sensitivity to
      PI-PLC are directly involved in coupling Thy-1 aggregation to transmembrane
      signaling.

PMID- 9645367
TI  - Distinct roles of the interleukin-7 receptor alpha chain in fetal and adult
      thymocyte development revealed by analysis of interleukin-7 receptor alpha
      deficient mice.
AB  - Mouse mutants lacking expression of the IL-7 receptor (IL-7R) alpha chain are
      defective in thymopoiesis. The adult thymus has multiple defects, including
      reduced cell numbers and proportions of the more mature thymocyte subsets, a
      complete absence of CD25+ cells and a reduced level of RAG1 and RAG2 expression.
      We show here that, in contrast to the profound developmental arrest observed in
      the adult thymus, fetal thymocytes from IL-7Ralpha-/- mice have normal
      proportions of all of the major thymocyte subpopulations, including CD25+
      thymocytes and the most mature single-positive subsets. Moreover, normal levels
      of RAG1 and RAG2 were observed. Total thymocyte numbers, however, remained
      reduced. These data suggest that the IL-7Ralpha chain is a key regulator of both
      survival and proliferation during thymocyte development but that it is not
      essential for the production of T cells during fetal thymopoiesis.

PMID- 9645368
TI  - The antigen presentation pathway in medullary thymic epithelial cells, but not
      that in cortical thymic epithelial cells, conforms to the endocytic pathway.
AB  - Murine medullary thymic epithelial cells (mTEC), but not cortical thymic
      epithelial cells (cTEC), are able to present a soluble antigen, ovalbumin, to
      helper T cells (Mizuochi, T. et al., J. Exp. Med. 1992. 175: 1601-1605). This
      functional difference between the mTEC and the cTEC is particularly important
      when we consider the thymic selection of the T cell repertoire. In the previous
      report, we proposed that mTEC and cTEC utilize two distinct antigen
      processing/presenting pathways (Kasai, M. et al., Eur. J. Immunol. 1996. 26: 2101
      2107). In this report, we further confirmed this difference by analyzing (a)
      localization of MHC class II, H2-DM, and invariant chain (li) molecules, (b) the
      biochemical nature of MHC class II molecules, (c) the sensitivity of MHC class II
      alphabeta heterodimer formation to concanamycin A, a vacuolar H+-ATPase
      inhibitor, and (d) the subcellular distribution of MHC class II, H2-DM, and li
      molecules, in both TEC. Our results demonstrated that, in the mTEC, MHC class II,
      H2-DM and li molecules gain access to the endocytic pathway, where the luminal
      condition is acidic and thus li molecules are efficiently degraded and H2-DM
      molecules function well. In the cTEC, however, such molecules seemed to gain
      access to an alternative transport pathway, e.g. a secretory pathway, where the
      luminal condition is not fully acidic. These two distinct antigen processing
      pathways may account for the functional difference between mTEC and cTEC.

PMID- 9645369
TI  - Involvement of phosphoinositide 3-kinase and Rac in membrane ruffling induced by
      IL-2 in T cells.
AB  - IL-2 is known to play a critical role in regulating T lymphocyte proliferation.
      We show here that IL-2 also provokes an instantaneous and sustained membrane
      ruffling in cloned human or murine T cells as well as in lectin-activated
      peripheral blood lymphocytes. In the IL-2-induced lamellipodia, tubulin is
      depolymerized whereas actin is strongly polymerized, forming caps. IL-2-induced
      membrane ruffling is protein kinase C (PKC) independent, as judged by the absence
      of effects of bisindolylmaleimide, an efficient inhibitor of all PKC isoforms.
      The formation of lamellipodia by IL-2 is blocked by wortmannin and LY294002, two
      inhibitors of phosphoinositide 3-kinase (PI3-kinase). Moreover, expression in
      murine T cells of an inactive form of P13-kinase inhibits IL-2-induced membrane
      ruffling, whereas expression of a constitutively active p110 increases the basal
      membrane ruffling. Rac is also involved in IL-2-induced membrane ruffling since
      an inactive form of Rac (N17rac) blocks the IL-2-induced lamellipodia, whereas
      the constitutive form of Rac (Val12rac) can also lead to membrane ruffling. In
      the signaling cascade, Rac is downstream of PI3-kinase since constitutive
      membrane ruffling in Val12rac cells is insensitive to wortmannin. Thus, through a
      signaling cascade involving PI3-kinase and Rac, IL-2 can induce profound
      alterations of the T cell cytoskeleton, a phenomenon which might be of importance
      for T cell physiology.

PMID- 9645370
TI  - Thymic function in young/old chimeras: substantial thymic T cell regenerative
      capacity despite irreversible age-associated thymic involution.
AB  - Age-associated thymic involution results in a diminished capacity to regenerate T
      cell populations, although the magnitude of this effect is unknown. In this
      report, thymic function was studied in aged vs. young adult mice after lethal
      irradiation and administration of T cell-depleted bone marrow (BM) from young
      mice. Abnormalities observed in aged thymi (reduced thymocyte numbers, histologic
      abnormalities) were not reversed by administration of young BM via bone marrow
      transplantation (BMT), but aged thymi displayed a normal thymocyte subset
      distribution and appropriately deleted MIs-reactive T cells after BMT. Aged BMT
      recipients regenerated significantly reduced numbers of splenic T cells compared
      to young recipients and showed increased peripheral expansion of thymic emigrants
      since a higher proportion of BM-derived T cells expressed a memory phenotype in
      aged vs. young BMT recipients. Because peripheral expansion of thymic emigrants
      could substantially increase the number of thymic progeny present in the spleen,
      we sought to measure thymic T cell regenerative capacity after BMT in a setting
      devoid of peripheral expansion. To do this, TCR-transgenic (Tg+) T cell-depleted
      BM was administered to aged and young recipients lacking antigen specific for the
      Tg+ TCR. Aged recipients regenerated approximately 50 % of the TCR Tg+ cells
      regenerated in young BMT recipients, providing evidence that even very aged thymi
      retain the capacity to regenerate significant numbers of mature T cell progeny.
      Therefore, thymic function is reduced with aged but it is not lost, suggesting
      that therapeutic approaches to enhance thymic function may be successful even in
      very aged hosts.

PMID- 9645371
TI  - T cell recognition motifs of an immunodominant peptide of myelin basic protein in
      patients with multiple sclerosis: structural requirements and clinical
      implications.
AB  - Myelin basic protein (MBP)-reactive T cells may play an important role in the
      pathogenesis of multiple sclerosis (MS). The T cell response to the 83-99 region
      of MBP represents a dominant autoreactive response to MBP in MS patients of DR2
      haplotype. In this study, a large panel of DR2- and DR4-restricted T cell clones
      specific for the MBP83-99 peptide were examined for the recognition motifs and
      structural requirements for antigen recognition using alanine-substituted
      peptides. Our study revealed that although the recognition motifs of the T cell
      clones were diverse, the TCR contact residues within the 83-99 region of MBP were
      highly conserved. Two central residues (Phe90 and Lys91) served as the critical
      TCR contact points for both DR2- and DR4-restricted T cell clones. Single alanine
      substitution at residue 90 or residue 91 abolished the responses of 81-95 % of
      the T cell clones while a double alanine substitution rendered all T cell clones
      unresponsive. It was also demonstrated in this study that the substituted
      peptides altered the cytokine profile of some, but not all, T cell clones. Some
      MBP83-99-specific T cell clones were able to sustain alanine substitutions and
      were susceptible to activation by microbial antigens. The study has an important
      implication in designing a peptide-based therapy for MS.

PMID- 9645372
TI  - Identification of mimicry peptides based on sequential motifs of epitopes derived
      from 65-kDa glutamic acid decarboxylase.
AB  - Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease with a
      predominantly non-hereditary etiology that results in a destruction of pancreatic
      beta cells by autoaggressive T lymphocytes. Neither the mechanism of initial
      stimulation of these T cells nor the nature of the environmental factors
      implicated in the disease have so far been identified. However, both issues are
      taken into account by the hypothesis of initial T cell activation by viral or
      bacterial mimicry peptides with sequence similarities to pancreatic self
      antigens. We determined sequential epitope motifs to search for mimicry peptides
      stimulating T cell lines specific for two epitopes derived from the IDDM
      autoantigen 65-kDa glutamic acid decarboxylase (GAD65). These were GAD65 (88-99),
      presented by HLA-DRB1*0101, and GAD65 (248-257), presented by HLA-DRB5*0101. T
      cell stimulation by peptides with substitutions in HLA anchor or T cell contact
      positions was analyzed to establish degenerate epitope motifs for database
      searching. Out of 28 tested candidate mimicry peptides derived from bacterial,
      viral and human proteins, 3 stimulated T cell lines and a T cell clone specific
      for epitope GAD65 (248-257). Our results demonstrate that mono- and polyclonal
      GAD65-specific T cells from IDDM patients can be stimulated by viral and
      bacterial peptides with little apparent sequence homology with autoantigenic
      epitopes. Moreover, in a synopsis with related published studies, our findings
      suggest that simple degenerate search motifs comprising principal T cell contacts
      plus HLA class II binding motifs may suffice to identify most mimicry peptides.

PMID- 9645373
TI  - Self-veto mechanism of CD8+ cytotoxic effector T cells. Peptide-induced paralysis
      affects the peptide-MHC-recognizing cytotoxic T lymphocytes and is independent of
      Fas/Fas ligand interactions.
AB  - The lytic activity of CD8+ cytotoxic T lymphocyte (CTL) cell lines or clones can
      be inhibited by addition of the peptide recognized by these cells. The mechanisms
      underlying this phenomenon are not fully understood. Here we have analyzed
      peptide-induced CTL paralysis using in vivo generated ovalbumin (OVA)-specific
      CTL. Lytic activity of OVA-specific CTL was inhibited by addition of the
      immunodominant OVA-peptide SIINFEKL in a dose-dependent manner. Paralysis was
      induced rapidly and binding of the peptide to MHC class I molecules was required.
      Using mixing experiments with CTL populations of different peptide specificities
      restricted to the same MHC class I molecule we identified a veto-like mechanism:
      the cytotoxic activity of the peptide-recognizing CTL was inhibited while the
      lytic activity of the peptide-presenting CTL was unaltered. Only CD8+ CTL but not
      CD4+ T cells or B+ cells induced paralysis. After removal of the peptide
      presenting CTL by magnetic cell sorting, paralysis was maintained and paralyzed
      CTL showed no signs of apoptosis. Loss of cytotoxicity could be induced in CTL
      populations from Fas-deficient (lpr+/lpr+) or Fas ligand-deficient (gld+/gld+)
      mice and mixtures thereof, implying that Fas/Fas ligand interactions are not
      involved during induction of paralysis. Hence, peptide-induced paralysis of CTL
      is due to a self-veto mechanism rather than to mutual killing of CTL. These
      findings may have implications for in vivo immunization with peptides, viral
      escape and peripheral tolerance mechanisms.

PMID- 9645374
TI  - Dendritic cell/macrophage precursors capture exogenous antigen for MHC class I
      presentation by dendritic cells.
AB  - Presentation of MHC class I antigens by professional antigen-presenting cells
      (APC) is an important pathway in priming cytotoxic T lymphocyte responses in
      vivo. This study sought to identify the nature of the professional APC
      responsible for indirect class I presentation by examining a special feature of
      professional APC, namely their ability to process exogenous forms of antigen for
      class I presentation. Incubation of highly purified bone marrow-derived precursor
      cells with chicken ovalbumin (OVA) led to the efficient presentation of the major
      class I-restricted OVA determinant by mature dendritic cells (DC), but not by
      macrophages (Mphi) derived from the precursor population. DC as well as
      macrophages were, however, able to mediate class II presentation of OVA,
      suggesting that macrophages were deficient in class I processing but not in
      capturing exogenous OVA. The majority of mature DC, i.e. over 80 %, generated
      from the precursor cells pulsed with OVA, presented the class I OVA epitope. Upon
      maturation, class I presentation of OVA by DC was greatly reduced, suggesting
      that class I processing of exogenous antigen is modulated during DC maturation in
      a manner similar to class II antigen processing. This study shows that bone
      marrow-derived DC/ME progenitors capture exogenous antigen for class I
      presentation, and that cells of the DC lineage can be functionally distinguished
      from cells of the macrophage lineage based on their ability to process exogenous
      antigen for class I presentation.

PMID- 9645375
TI  - Naturally activated CD4+ T cells are highly enriched for cytokine-producing
      cells.
AB  - Most T cells in a normal non-immunized individual are in a resting state.
      However, a small proportion of splenic T cells are large activated cells both in
      specific pathogen-free and antigen-free mice. To further elucidate the effector
      functions associated with these "naturally" activated CD4+ T cells, we have
      characterized the expression of various membrane markers, cytokine production and
      T helper activity by these cells. We show that naturally activated CD4+ T cells
      express activation markers and contain tenfold higher proportions of cells
      producing IL-4, IL-10 and IFN-gamma as compared to small CD4+ T cells. Despite
      the high proportion of IFN-gamma producers, naturally activated CD4+ T cells
      still induce B cell proliferation and differentiation. These results are
      discussed in the context of normal physiological autoreactivity.

PMID- 9645376
TI  - T cell cross-reactivity to heavy metals: identical cryptic peptides may be
      presented from protein exposed to different metals.
AB  - The mechanisms by which metals induce activation of T cells and thus produce
      allergic and/ or autoimmune reactions are still obscure, and the same is true for
      the mechanisms that underly T cell cross-reactivity to different heavy metal
      ions. In the present study, we investigated induction by metals of T cell
      reactions to cryptic peptides of bovine RNase A. Murine CD4+ T cell hybridomas
      specific for cryptic RNase peptides presented from Au(III)-treated RNase were
      used as detection probes. We showed that in vitro treatment of RNase with Pd(II),
      Pd(IV), Ni(IV), and partially Pt(IV), but not Au(I), Ni(II), or Pt(II), induced
      presentation of the same cryptic peptides as those presented from Au(III)-treated
      RNase. That the former heavy metal ions, but not the latter, were able to alter
      the antigenicity of RNase was reflected by their ability to induce conformational
      changes of RNase, as detected by circular dichroism spectroscopy. Furthermore,
      upon immunization against RNase pretreated with these metals, CD4+ T cell
      hybridomas specific for unidentified cryptic peptides were obtained. In
      conclusion, "metal-specific" T cell reactions may be directed against cryptic
      peptides, and metal cross-reactivity in allergic individuals might be due to
      metal-induced presentation of overlapping, but not identical, panels of cryptic
      peptides.

PMID- 9645377
TI  - Ligation of CD31/PECAM-1 modulates the function of lymphocytes, monocytes and
      neutrophils.
AB  - CD31 or platelet/endothelial cell adhesion molecule (PECAM-1) is a 130-kDa
      glycoprotein expressed on endothelial cells, granulocytes, a subset of
      lymphocytes and platelets. In this study, we examined the ability of four
      monoclonal antibodies (mAb) against different domains of CD31 to modulate the
      function of T lymphocytes, monocytes and neutrophils. Engagement of CD31 on T
      lymphocytes results in co-stimulation of T lymphocyte proliferation to suboptimal
      doses of anti-CD31 mAb. This proliferation is accompanied by secretion of
      numerous cytokines and chemokines, up-regulation of CD25 and an increase in cell
      size. Purification of T lymphocytes into CD45RO and CD45RA subsets showed that
      only naive CD45RA T lymphocytes are co-stimulated by anti-CD31 mAb. Further
      studies on neutrophils show that engagement of CD31 results in down-regulation of
      CD62L and up-regulation of CD11b/CD18 as well as oxidative burst, as assessed by
      superoxide release. In addition, ligation of CD31 on monocytes results in TNF
      alpha secretion, and studies with various cell signaling inhibitors indicate that
      tyrosine kinases and cAMP-dependent kinases are involved in monocyte activation
      via CD31. Of the four mAb used in this study, only two activated human
      leukocytes. These mAb were PECAM-1.3 and hec7, which bind to domains 1 and 2 of
      CD31. We conclude that engagement of domains 1 and 2 of CD31 results in outside
      in signaling in leukocytes.

PMID- 9645378
TI  - Transendothelial migration and trafficking of leukocytes in LFA-1-deficient mice.
AB  - The leukocyte integrin LFA-1 plays an important role in leukocyte trafficking and
      the immune response. Using LFA-1-deficient mice, we demonstrate that LFA-1
      regulates the trafficking of lymphocytes to peripheral lymph nodes, and, to a
      lesser degree, to mesenteric lymph nodes and acute inflammatory sites. LFA-1,
      either because of its role in initial adhesion and/ or the passage of leukocytes
      across endothelial cells, plays a vital role in T lymphocyte and neutrophil
      transendothelial migration. Neutrophils and activated T lymphocytes from LFA-1
      deficient mice were unable to cross endothelial cell monolayers in response to a
      chemokine gradient, whereas wild-type (WT) T lymphocytes and neutrophils were
      capable of migration. By contrast, LFA-1-deficient T lymphocytes displayed normal
      chemotaxis to the same chemokine. Our studies with LFA-1-deficient monocytes
      indicate that LFA-1 acts in concert with complement receptor 3 to mediate
      transendothelial migration of these cells, as anti-CD18 monoclonal antibodies
      (mAb) blocked both WT and LFA-1-deficient monocyte transendothelial migration,
      whereas anti-CD11 b mAb preferentially blocked transendothelial migration of LFA
      1-deficient monocytes. Finally, whereas anti-CD31 mAb blocked WT monocyte and
      neutrophil transendothelial cell migration they did not block LFA-1-deficient
      monocyte and neutrophil transendothelial migration.

PMID- 9645379
TI  - Contribution of CD11a/CD18, CD11b/CD18, ICAM-1 (CD54) and -2 (CD102) to human
      monocyte migration through endothelium and connective tissue fibroblast barriers.
AB  - Recently we reported that monocyte migration through a barrier of human synovial
      fibroblasts (HSF) is mediated by the CD11/CD18 (beta2) integrins, and the beta1
      integrins VLA-4 and VLA-5 on monocytes. Here we investigated in parallel the role
      of beta2 integrin family members, LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) on
      monocytes, and the immunoglobulin supergene family members, ICAM-1 and ICAM-2 on
      HSF and on human umbilical vein endothelial cells (HUVEC), in monocyte migration
      through HSF and HUVEC monolayers. Using function blocking monoclonal antibodies
      (mAb), when both VLA-4 and VLA-5 on monocytes were blocked, treatment of
      monocytes with mAb to both LFA-1 and to Mac-1 completely inhibited monocyte
      migration across HSF barriers, although blocking either of these beta2 integrins
      alone had no effect on migration, even when VLA-4 and VLA-5 were blocked. This
      indicates that optimal beta2 integrin-dependent monocyte migration in synovial
      connective tissue may be mediated by either LFA-1 or Mac-1. Both ICAM-1 and ICAM
      2 were constitutively expressed on HSF and on HUVEC, although ICAM-2 was only
      minimally expressed on HSF. Based on results of mAb blockade, ICAM-1 appeared to
      be the major ligand for LFA-1-dependent migration through the HSF. In contrast,
      both ICAM-1 and ICAM-2 mediated LFA-1-dependent monocyte migration through HUVEC.
      However, neither ICAM-1 nor ICAM-2 was required for Mac-1 -dependent monocyte
      migration through either cell barrier, indicating that Mac-1 can utilize ligands
      distinct from ICAM-1 and ICAM-2 on HSF and on HUVEC during monocyte
      transmigration.

PMID- 9645380
TI  - p49, a putative HLA class I-specific inhibitory NK receptor belonging to the
      immunoglobulin superfamily.
AB  - NK cells display several killer inhibitory receptors (KIR) specific for different
      alleles of MHC class I molecules. A family of KIR are represented by type I
      transmembrane proteins belonging to the immunoglobulin superfamily (Ig-SF).
      Besides cDNA encoding for these KIR, additional cDNA have been identified which
      encode for Ig-SF receptors with still undefined specificity. Here we analyze one
      of these cDNA, termed cl.15.212, which encodes a type I transmembrane protein
      characterized by two extracellular Ig-like domains and a 115-amino acid
      cytoplasmic tail containing a single immuno-receptor tyrosine-based inhibitory
      motif (ITIM) which is typical of KIR. cl.15.212 cDNA displays approximately 50 %
      sequence homology with other Ig-SF members. Different from the other KIR,
      cl.15.212 mRNA is expressed by all NK cells and by a fraction of KIR+ T cell
      clones. cl.15.212 cDNA codes for a membrane-bound receptor displaying an apparent
      molecular mass of 49 kDa, thus termed p49. To determine the specificity of the
      cl.15.212-encoded receptor, we generated soluble fusion proteins consisting of
      the ectodomain of p49 and the Fc portion of human IgG1. Soluble molecules bound
      efficiently to 221 cells transfected with HLA-G1, -A3, -B46 alleles and weakly to
      -B7 allele. On the other hand, they did not bind to 221 cells either
      untransfected or transfected with HLA-A2, -B51, -Cw3 or -Cw4. The binding
      specificity of soluble p49-Fc was confirmed by competition experiments using an
      anti-HLA class I-specific monoclonal antibody. Finally, different cDNA encoding
      for molecules homologous to cl.15.212 cDNA have been isolated, two of which lack
      the sequence encoding the transmembrane portion, thus suggesting they may encode
      soluble molecules.

PMID- 9645381
TI  - NK cells differentiated from bone marrow, cord blood and peripheral blood stem
      cells exhibit similar phenotype and functions.
AB  - In the present study, we investigated the differentiation of human NK cells from
      bone marrow, cord blood and mobilized peripheral blood purified CD34+ stem cells
      using a potent culture system. Elutriated CD34+ stem cells were grown for several
      weeks in medium supplemented with stem cell factor (SCF) and IL-15 in the
      presence or absence of a murine stromal cell line (MS-5). Our data indicate that
      IL-15 induced the proliferation and maturation of highly positive CD56+ NK cells
      in both types of culture, although murine stromal cells slightly increased the
      proliferation of NK cells. NK cells differentiated in the presence of MS-5 were
      mostly CD56+ CD7 and a small subset expressed CD16. These in vitro differentiated
      CD56+ NK cells displayed cytolytic activity against the HLA class I- target K562.
      The CD56+ CD16+ subset also lysed NK-resistant Daudi cells. Neither of these NK
      subsets were shown to express Fas ligand. Total CD56+ cells expressed high
      amounts of transforming growth factor-beta and granulocyte-macrophage colony
      stimulating factor, but no IFN-gamma. Investigation of NK receptor expression
      showed that most CD56+ cells expressed membrane CD94 and NKG2-A mRNA. PCR
      analysis revealed that p58 was also expressed in these cells. The role of CD94 in
      NK cell-mediated cytotoxicity was assessed on human HLA-B7-transfected murine L
      cells. While a low cytotoxic activity towards HLA-B7 cells was observed, the HLA
      DR4 control cells were killed with high efficiency. These studies demonstrate
      that cytolytic and cytokine-producing NK cells may be derived from adult and
      fetal precursors by IL-15 and that these cells express a CD94 receptor which may
      influence their lytic potential.

PMID- 9645382
TI  - Th1 cells induce and Th2 inhibit antigen-dependent IL-12 secretion by dendritic
      cells.
AB  - Dendritic cells are the most relevant antigen-presenting cells (APC) for
      presentation of antigens administered in adjuvant to CD4+ T cells. Upon
      interaction with antigen-specific T cells, dendritic cells (DC) expressing
      appropriate peptide-MHC class II complexes secrete IL-12, a cytokine that drives
      Th1 cell development. To analyze the T cell-mediated regulation of IL-12
      secretion by DC, we have examined their capacity to secrete IL-12 in response to
      stimulation by antigen-specific Th1 and Th2 DO11.10 TCR-transgenic cells. These
      cells do not differ either in TCR clonotype or CD40 ligand (CD40L) expression.
      Interaction with antigen-specific Th1, but not Th2 cells, induces IL-12 p40 and
      p75 secretion by DC. The induction of IL-12 production by Th1 cells does not
      depend on their IFN-gamma secretion, but requires direct cell-cell contact
      mediated by peptide/MHC class II-TCR and CD40-CD40L interactions. Th2 cells not
      only fail to induce IL-12 secretion, but they inhibit its induction by Th1 cells.
      Unlike stimulation by Th1, inhibition of IL-12 production by Th2 cells is
      mediated by soluble molecules, as demonstrated by transwell cultures. Among Th2
      derived cytokines, IL-10, but not IL-4 inhibit Th1-driven IL-12 secretion. IL-10
      produced by Th2 cells appears to be solely responsible for the inhibition of Th1 
      induced IL-12 secretion, but it does not account for the failure of Th2 cells to
      induce IL-12 production by DC. Collectively, these results demonstrate that Th1
      cells up-regulate IL-12 production by DC via IFN-gamma-independent cognate
      interaction, whereas this is inhibited by Th2-derived IL-10. The inhibition of
      Th1 -induced IL-12 production by Th2 cells with the same antigen specificity
      represents a novel mechanism driving the polarization of CD4+ T cell responses.

PMID- 9645383
TI  - Inhibition of in vitro immunoglobulin production by IL-12 in murine chronic graft
      vs.-host disease: synergism with IL-18.
AB  - We investigated the effects of IL-12 on immunoglobulin (Ig) production in vitro
      in murine chronic graft-vs. -host disease (cGVHD), a lupus-like model of overt B
      cell activation induced by allogeneic stimulation. Addition of IL-12 to cGVHD
      splenocytes strongly inhibited total Ig (Igkappa), IgM and IgG1 production.
      Although IL-12 down-regulated IL-4, IL-5, IL-9 and IL-10 production, its
      inhibitory activity on Ig production could not be ascribed to down-regulation of
      these cytokines, as addition of saturating doses of IL-4, IL-5 and/or IL-9 did
      not reverse the inhibitory activity of IL-12. Interestingly, IL-12 was also found
      to suppress the stimulating effect of IL-4 and IL-5 on Ig synthesis by cGVHD
      splenocytes. Several lines of evidence indicated that the inhibitory activity
      exerted by IL-12 on Ig production was mediated by IFN-gamma. First, IFN-gamma was
      produced in large amounts upon IL-12 stimulation. Secondly, it displayed a potent
      inhibitory activity on Ig production. Thirdly, Ig production was also inhibited
      by IL-18, a recently cloned IFN-gamma-inducing cytokine. Finally, the inhibitory
      activity of IL-12 was blocked by anti-IFN-gamma monoclonal antibody. We also
      investigated whether IL-12 down-regulated Ig production by purified cGVHD B
      cells. We found that IL-12 had only a marginal inhibitory activity on highly
      purified B cell populations isolated from cGVHD splenocytes and stimulated with
      IL-4 and IL-5, and that IL-18 was inactive in this respect. However, when the two
      cytokines were combined, a striking synergy was unmasked not only for IgG1
      inhibition but also for IFN-gamma production by these B cell populations. Taken
      together, our results demonstrate that IL-12 inhibits in vitro Ig production by
      activated splenocytes through IFN-gamma production and that it synergizes with IL
      18 on activated B cells to inhibit Ig production, through up-regulation of IFN
      gamma production by B cells.

PMID- 9645384
TI  - The chemokine SLC is expressed in T cell areas of lymph nodes and mucosal
      lymphoid tissues and attracts activated T cells via CCR7.
AB  - Secondary lymphoid-tissue chemokine, SLC, also known as exodus-2 and 6Ckine, is a
      novel CC chemokine with selectivity for T lymphocytes and preferential expression
      in lymphoid tissues. We have studied its production, receptor usage and
      biological activities. High levels of SLC mRNA were detected in lymph nodes, the
      gastrointestinal tract and several gland tissues, but no expression was found by
      Northern blot analysis in freshly isolated or stimulated blood monocytes and
      lymphocytes, or neutrophils and eosinophils. In situ hybridization revealed
      constitutive expression of SLC in the T cell areas and the marginal zone of
      follicles in lymph nodes and the mucosa-associated lymphoid tissue, but not in B
      cell areas or sinuses. Comparison with immunocytochemical staining showed
      similarity between the in situ expression of SLC and the distribution of
      interdigitating dendritic cells but not with sinus-lining dendritic cells,
      macrophages or T lymphocytes. SLC induced chemotaxis of T lymphocytes and its
      activity increased considerably when the cells were conditioned with IL-2 or
      phytohemagglutinin (PHA). Under optimal conditions SLC had unusually high
      efficacy and induced the migration of up to 50 % of input T lymphocytes. SLC also
      induced Ca2+ mobilization in these cells. Similar responses were obtained with
      EBI1 ligand chemokine (ELC), and sequential stimulation with both chemokines led
      to cross-desensitization, suggesting that SLC acts via the ELC receptor, CCR7.
      This was confirmed using murine pre-B cells stably transfected with CCR7 which
      bound SLC with high affinity and showed chemotaxis and Ca2+ mobilization in
      response to both SLC and ELC. In T lymphocytes PHA and IL-2, which enhanced
      chemotactic responsiveness, also markedly enhanced CCR7 expression. In contrast
      to all known chemokine receptors, up-regulation of CCR7 by IL-2 was transient. A
      maximum was reached in 2-3 days and expression returned to initial levels within
      8-10 days. The present study shows that SLC is constitutively produced within the
      T cell areas of secondary lymphoid organs and attracts T lymphocytes via CCR7.

PMID- 9645385
TI  - Suppression of experimental autoimmune encephalomyelitis with a TNF binding
      protein (TNFbp) correlates with down-regulation of VCAM-1/VLA-4.
AB  - The effect of a novel TNF binding protein (TNFbp), a polyethylene glycol-linked
      form of the type I soluble receptor of TNF, on the expression of adhesion
      molecules has been investigated with a passive transfer model of experimental
      autoimmune encephalomyelitis (EAE) in SJL/J mice. The expression of L-selectin,
      VLA-4 and LFA-1 on spleen cells of EAE animals treated with TNFbp or saline was
      examined by FACS analysis. The expression of VCAM-1 and ICAM-1 was investigated
      by immunochemistry in spinal cord tissue of SJL/J mice with EAE. In animals
      sensitized for EAE and treated with TNFbp, the expression of VCAM-1 in the
      central nervous system as well as VLA-4 on spleen cells was clearly diminished.
      Reduction in VCAM-1 staining and VLA-4 expression corresponded to inhibition of
      inflammation in the spinal cord and to prevention of clinical signs of EAE. The
      results have also shown that myelin basic protein responses as well as non
      antigen-specific responses were not diminished in animals treated with TNFbp. The
      findings suggest that TNFbp might prevent EAE development by modulating the
      expression of VCAM-1 and VLA-4.

PMID- 9645386
TI  - Bacterial DNA and immunostimulatory CpG oligonucleotides trigger maturation and
      activation of murine dendritic cells.
AB  - Bacterial DNA and immunostimulatory (i.s.) synthetic CpG-oligodeoxynucleotides
      (ODN) act as adjuvants for Th1 responses and cytotoxic T cell responses to
      proteinaceous antigens. Dendritic cells (DC) can be referred to as "nature's
      adjuvant" since they display the unique capacity to sensitize naive T cells.
      Here, we demonstrate that bacterial DNA or i.s. CpG-ODN cause simultaneous
      maturation of immature DC and activation of mature DC to produce cytokines. These
      events are associated with the acquisition of professional antigen-presenting
      cell (APC) function. Unfractionated murine bone marrow-derived DC and FACS
      fractionated MHC class IIlow (termed immature DC) or MHC class IIhigh populations
      (termed mature DC) were stimulated with bacterial DNA or i.s. CpG-ODN. Similar to
      lipopolysaccharide, i.s. CpG-ODN caused up-regulation of MHC class II, CD40 and
      CD86, but not CD80 on immature and mature DC. In parallel both DC subsets were
      activated to produce large amounts of IL-12, IL-6 and TNF-alpha. CpG-ODN
      activated DC displayed professional APC function in allogeneic mixed lymphocyte
      reaction and in staphylococcal enterotoxin B-driven naive T cell responses. We
      interpret these findings to mean that bacterial DNA and i.s. CpG-ODN cause
      maturation (first step) and activation (second step) of DC to bring about
      conversion of immature DC into professional APC.

PMID- 9645387
TI  - Hypothesis: are fatty acid patterns characteristic of essential fatty acid
      deficiency indicative of oxidative stress?
AB  - Several unrelated diseases show plasma and tissue fatty acid patterns
      characteristic of those seen in Essential Fatty Acid Deficiency Disease (EFADD).
      A common feature occurring in all these diseases is oxidative stress. We
      hypothesize that reactive oxygen species or products of oxidative damage,
      particularly those derived from lipids, act as signal molecules to alter
      desaturase enzymes and induce the fatty acid patterns characteristic of EFADD.

PMID- 9645388
TI  - The oxidative inactivation of tissue inhibitor of metalloproteinase-1 (TIMP-1) by
      hypochlorous acid (HOCI) is suppressed by anti-rheumatic drugs.
AB  - Tissue inhibitors of metalloproteinases (TIMPs) prevent uncontrolled connective
      tissue destruction by limiting the activity of matrix metalloproteinases (MMPs).
      That TIMPs should be susceptible to oxidative inactivation is suggested by their
      complex tertiary structure which is dependent upon 6 disulphide bonds. We
      examined the oxidative inactivation of human recombinant TIMP-1 (hr TIMP-1) by
      HOCl and the inhibition of this process by anti-rheumatic agents. TIMP-1 was
      exposed to HOCl in the presence of a variety of disease modifying anti-rheumatic
      drugs. TIMP-1 activity was measured by its ability to inhibit BC1 collagenase
      activity as measured by a fluorimetric assay using the synthetic peptide
      substrate (DNP-Pro-Leu-Ala-Leu-Trp-Ala-Arg), best cleaved by MMP-1. The
      neutrophil derived oxidant HOCl, but not the derived oxidant N-chlorotaurine, can
      inactivate TIMP-1 at concentrations achieved at sites of inflammation. Anti
      rheumatic drugs have the ability to protect hrTIMP-1 from inactivation by HOCl.
      For D-penicillamine, this effect occurs at plasma levels achieved with patients
      taking the drug but for other anti-rheumatic drugs tested this occurs at
      relatively high concentrations that are unlikely to be achieved in vivo, except
      possibly in a microenvironment. These results are in keeping with the concept
      that biologically derived oxidants can potentiate tissue damage by inactivating
      key but susceptible protein inhibitors such as TIMP-1 which form the major local
      defence against MMP induced tissue breakdown.

PMID- 9645389
TI  - Studies of the cellular distribution of superoxide dismutases in adult and fetal
      rat tissues.
AB  - Activities of three types of superoxide dismutase in tissue fractions were
      significantly lower in fetal and adult brain and fetal limb preparations than in
      fetal and adult heart preparations. An exception was the cytoplasmic fraction of
      adult brain that had levels of Cu, Zn-superoxide dismutase activity comparable to
      those in cytoplasmic fractions of heart. In addition, Mn superoxide dismutase
      activity appeared to be very low in all fetal mitochondrial matrix fractions and
      cytoplasmic fractions as well as in adult brain. Finally, the results of these
      studies emphasize the importance of two antioxidant defense systems in the
      tissues studied, one associated with the mitochondrial electron transport system
      and the other, the cytosolic Cu, Zn enzyme.

PMID- 9645390
TI  - Prevention of intracellular oxidative stress to lens by pyruvate and its ester.
AB  - Pyruvate is a well-known scavenger of hydrogen peroxide (H2O2). In addition, it
      scavenges superoxide radical (O2.-). However, evidence on its intracellular
      antioxidant function is meager at present. Hence, we have examined the
      effectiveness of this metabolite and its ethyl ester against intracellular
      oxidative damage to the lens under organ culture. Menadione, a redoxcycling
      quinone, was used to generate the reactive oxygen species (ROS). It was found to
      inhibit lens metabolism as evidenced by a decrease of ATP. Additionally, tissue
      oxidation was apparent by loss of glutathione (GSH), and increase in the level of
      oxidized glutathione (GSSG), coupled with increase of the urea soluble proteins
      (water insoluble). The overall physiological damage was apparent by the
      inhibition of the Na+-K+-ATPase dependent cation pump, as evidenced by a
      decreased rubidium transport. These deleterious effects were attenuated by
      pyruvate and ethyl-pyruvate. The later was found to be more effective.

PMID- 9645391
TI  - Evidence against the involvement of multiple radical generating sites in the
      expression of the vascular cell adhesion molecule-1.
AB  - The present study was undertaken to investigate the hypothesis that multiple
      oxygen radical generating systems contribute to the tumor necrosis factor (TNF)
      alpha-stimulated transcriptional activation of the vascular cell adhesion
      molecule (VCAM)-1 in endothelial cells. Experimental evidence has implicated the
      cytochrome P450 monooxygenase and a phagocyte type NADPH-oxidase as a source of
      oxygen radicals in these cells. We show here that endothelial cells exhibit
      cytochrome P450 activity by measuring the O-dealkylation of the exogenous
      substrate 7-ethoxyresorufin, but components of the phagocyte-type NADPH oxidase
      could not be demonstrated in endothelial cells. In that latter respect it was
      surprising that the NADPH oxidase inhibitor apocynin completely prevented the
      accumulation of VCAM-1 mRNA. However, we found that apocynin also acts as an
      inhibitor of cytochrome P450 activity in endothelial cells. Therefore the
      inhibitory effect of apocynin on the induction of VCAM-1 may no longer be used to
      demonstrate a role for the NADPH oxidase in this process. Furthermore, different
      cytochrome P450 inhibitors Co2+, metyrapone, SKF525a decreased the endothelial
      VCAM-1 expression stimulated by TNFalpha. Also under hypoxic conditions the
      expression of VCAM-1 was reduced. On this basis we assume that the oxygen
      dependent step in the intracellular signalling cascade underlying the TNFalpha
      stimulated transcriptional activation of VCAM-1 resides in the activity of a
      cytochrome P450 dependent monooxygenase. The finding that the phospholipase A2
      inhibitor bromophenacylbromide inhibited the expression of VCAM-1 may indicate
      that arachidonic acid serves as a substrate for the cytochrome P450 monooxygenase
      reaction, but further research is needed to elucidate the particular cytochrome
      P450 family member mediating the expression of VCAM-1.

PMID- 9645392
TI  - A reappraisal of xanthine dehydrogenase and oxidase in hypoxic reperfusion
      injury: the role of NADH as an electron donor.
AB  - Xanthine oxidase (XO) is conventionally known as a generator of reactive oxygen
      species (ROS) which contribute to hypoxic-reperfusion injury in tissues. However,
      this role for human XO is disputed due to its distinctive lack of activity
      towards xanthine, and the failure of allopurinol to suppress reperfusion injury.
      In this paper, we have employed native gel electrophoresis together with activity
      staining to investigate the role human xanthine dehydrogenase (XD) and XO in
      hypoxic reperfusion injury. This approach has provided information which cannot
      be obtained by conventional spectrophotometric assays. We found that both XD and
      XO of human umbilical vein endothelial cells (HUVECs) and lymphoblastic leukaemic
      cells (CEMs) catalysed ROS generation by oxidising NADH, but not hypoxanthine.
      The conversion of XD to XO was observed in both HUVECs and CEMs in response to
      hypoxia, although the level of conversion varied. Purified human milk XD
      generated ROS more efficiently in the presence of NADH than in the presence of
      hypoxanthine. This NADH oxidising activity was blocked by the FAD site inhibitor,
      diphenyleneiodonium (DPI), but was not suppressible by the molybdenum site
      inhibitor, allopurinol. However, in the presence of both DPI and allopurinol the
      activities of XD/XO were completely blocked with either NADH or hypoxanthine as
      substrates. We conclude that both human XD and XO can oxidise NADH to generate
      ROS. Therefore, the conversion of XD to XO is not necessary for post-ischaemic
      ROS generation. The hypoxic-reperfusion injury hypothesis should be reappraised
      to take into account the important role played by XD and XO in oxidising NADH to
      yield ROS.

PMID- 9645393
TI  - In vitro inhibition by N-acetylcysteine of oxidative DNA modifications detected
      by 32P postlabeling.
AB  - Reactive oxygen species are involved in the pathogenesis of cancer and other
      chronic degenerative diseases through a variety of mechanisms, including DNA
      damage. We investigated by 32p and 33P postlabeling analyses the nucleotidic
      modifications induced in vitro by treating calf thymus DNA with H2O2 and CuSO4,
      interacting in a Fenton type reaction. Six different enrichment procedures and
      three chromatographic systems were comparatively assayed. The chromatographic
      system using phosphate/urea, which is more suitable for detecting bulky DNA
      adducts, was rather insensitive. In contrast, the system using acetic
      acid/ammonium formate revealed high levels of mononucleotidic modifications. In
      terms of ratio of adduct levels in treated and untreated DNA, the enrichment
      procedures ranked as follows: nuclease P1 (19.6), no enrichment (18.3), digestion
      to trinucleotides (17.6), digestion to monophosphate mononucleotides (8.4),
      digestion to dinucleotides (3.4), and extraction with butanol (<1.0). The system
      using formic acid/ammonium formate was quite efficient in detecting 8-hydroxy-2'
      deoxyguanosine. Labeling with 33p further enhanced the sensitivity of the method.
      The oxidative damage was so intense to produce a strong DNA fragmentation
      detectable by agarose gel electrophoresis, and nucleotidic modifications were
      more intense when DNA fragmentation was greater. The DNA alterations produced by
      H2O2 alone were significantly lower than those produced following reaction of
      H2O2 with CuSO4. The thiol N-acetylcysteine (NAC) was quite efficient in
      inhibiting both nucleotidic modifications and DNA fragmentation produced in vitro
      by either H2O2 or the .OH generating system. These results support at a molecular
      level the findings of previous studies showing the ability of NAC to inhibit the
      genotoxicity of peroxides and of reactive oxygen species generated by electron
      transfer reactions.

PMID- 9645394
TI  - Nitric oxide production in human macrophagic cells phagocytizing opsonized
      zymosan: direct characterization by measurement of the luminol dependent
      chemiluminescence.
AB  - When differentiated into mature macrophages by the combination of all-trans
      retinoic acid and 1,25-dihydroxyvitamin D3, the human promonocytic cell lines
      U937 and THP-1 expressed inducible nitric oxide synthase (iNOS) transcripts.
      During their differentiation, the cells acquired the capacity to produce not only
      superoxide anion (O2.-) but also nitric oxide (.NO) in response to IgG (or IgE)
      opsonized zymosan. The inhibitors of the iNOS pathway, aminoguanidine and NG
      monomethyl-L-arginine (L-NMMA), suppressed the production of .NO and enhanced the
      steady-state concentration of O2.- determined. Conversely, superoxide dismutase
      (SOD) scavenged the O2.- released and increased the .NO-derived nitrite
      concentration detected. These data suggested a possible interaction between O2.-
      and .NO. In differentiated U937 (or THP-1) cells, IgG or IgE-opsonized zymosan
      induced a strong time-dependent luminol-dependent chemiluminescence (LDCL), which
      was abrogated by SOD and partially inhibited by aminoguanidine or L-NMMA. Since
      the iNOS inhibitors did not directly scavenge O2.-, LDCL determination in the
      presence or absence of SOD and/or iNOS inhibitors demonstrated a concomitant
      production of O2.- and .NO. These radicals induced the formation of a .NO-derived
      product(s), probably peroxynitrite (ONOO-), which was required to elicit maximal
      LDCL. Finally, LDCL measurement provided a convenient tool to characterize iNOS
      triggering and demonstrated an interaction between NADPH oxidase and iNOS
      products in human macrophagic cells phagocytizing opsonized-zymosan. These
      findings show that in activated macrophages, iNOS activity can be involved in
      LDCL and support the debated hypothesis of iNOS participation to the microbicidal
      activity of human macrophages.

PMID- 9645395
TI  - Peroxynitrite causes aspartate release from dissociated rat cerebellar granule
      neurones.
AB  - Peroxynitrite (ONOO-) is a powerful oxidant which is formed from the reaction
      between nitric oxide (NO) and superoxide anion. It has therefore been proposed to
      mediate the toxic actions caused by NO. Since ONOO- may be formed in the central
      nervous system (CNS) in pathological conditions such as brain ischaemia, we
      decided to investigate whether this molecule induces the release of the
      endogenous excitatory amino acids glutamate and aspartate from neurones. We
      selected as biological model acutely dissociated rat cerebellar granule neurones
      in suspension to allow a direct interaction between ONOO- and target cells.
      Peroxynitrite caused a concentration-dependent release of aspartate but not of
      glutamate from dissociated cerebellar granule neurones. Peroxynitrite-induced
      aspartate release was inhibited by dithiothreitol, tetrodotoxin, and in Na+
      deprived solutions and not affected by EGTA or pre-incubation with the cytosolic
      Ca2+ chelator BAPTA/AM. Peroxynitrite also induced an increase in intracellular
      Ca2+ concentration which was not affected in the presence of EGTA. These data
      show that ONOO- causes release of aspartate from cerebellar granule neurones and
      that this effect might arise from an alteration of Na+ membrane permeability
      leading subsequently to reversal of a Na+-dependent plasma membrane transporter
      of this excitatory amino acid. In addition, ONOO- alters Ca2+ homeostasis likely
      due to Na+ overload. Taken together, these findings may help and elucidate some
      of the intimate mechanisms of NO-induced neuronal damage in pathological
      circumstances.

PMID- 9645396
TI  - Chain-breaking antioxidants and ferriheme-bound drugs are synergistic inhibitors
      of erythrocyte membrane peroxidation.
AB  - Induced erythrocyte membrane peroxidation (EMP) is considered as an accurate
      model of reperfusion injuries and as such was used to investigate protective
      effects of various drugs. EMP was induced by an azo initiator and monitored by
      oxygen uptake. Both hydrophilic (ascorbic acid) and lipophilic (alpha-tocopherol,
      probucol, nicanartine) chain-breaking antioxidants as well as ferriheme-bound
      drugs (deferoxamine, chloroquine) inhibited EMP. When antioxidants and ferriheme
      bound drugs were combined, synergistic effects were observed. It is proposed that
      ferriheme compounds which catalyse peroxide induced lipid peroxidation were
      blocked by deferoxamine and/or chloroquine. So these drugs inhibited at least
      partly the membrane peroxidation process and added their effects to the ones of
      chain-breaking antioxidants.

PMID- 9645397
TI  - Reactivity of cartilage and selected carbohydrates with hydroxyl radicals: an NMR
      study to detect degradation products.
AB  - It was investigated to what extent isolated, monomeric and polymeric
      carbohydrates as well as cartilage specimens are affected by hydroxyl radicals
      generated by gamma-irradiation or Fenton reaction and what products can be
      detected by means of NMR spectroscopy. Resonances of all protons in glucose and
      other monosaccharides as well as carbon resonances in 13C-enriched glucose were
      continuously diminished upon gamma-irradiation. Formate and malondialdehyde were
      found as NMR detectable products in irradiated glucose solutions under
      physiologically relevant (aerated) conditions. In polysaccharide solutions (e.g.
      hyaluronic acid) gamma-irradiation and also treatment with the Fenton reagent
      caused first an enhancement of resonances according to mobile N-acetyl groups at
      2.02 ppm. This indicates a breakdown of glycosidic bonds in polysaccharides.
      Using higher radiation doses or higher concentrations of the Fenton reagent
      formate was also detected. The same sequence of events was observed upon
      treatment of bovine nasal cartilage with the Fenton reagent. First, glycosidic
      linkages in cartilage polysaccharides were cleaved and subsequently formate was
      formed. In contrast, collagen of cartilage was affected only to a very low
      extent. Thus, HO-radicals caused the same action on cartilage as on isolated
      polymer solutions, inducing a fragmentation of polysaccharides and the formation
      of formate.

PMID- 9645398
TI  - Redox properties of iron in the binding site(s) of F1ATPase from mammalian
      mitochondria and thermophilic bacterium PS3: a comparative study.
AB  - Iron ions in the two iron centers of beef heart mitochondrial F1ATPase, which we
      have been recently characterized (FEBS Letters 1996, 379, 231-235), exhibit
      different redox properties. In fact, the ATP-dependent site is able to maintain
      iron in the redox state of Fe(II) even in the absence of reducing agents, whereas
      in the nucleotide-independent site iron is oxidized to Fe(III) upon removal of
      the reductant. Fe(III) ions in the two sites display different reactivity towards
      H2O2, because only Fe(III) bound in the nucleotide-independent site rapidly
      reacts with H2O2 thus mediating a 30% enzyme inactivation. Thermophilic bacterium
      PS3 bears one Fe(III) binding site, which takes up Fe(III) either in the absence
      or presence of nucleotides and is unable to maintain iron in the redox state of
      Fe(II) in the absence of ascorbate. Fe(III) bound in thermophilic F1ATPase in a
      molar ratio 1:1 rapidly reacts with H2O2 mediating a 30% enzyme inactivation.
      These results support the presence in mitochondrial and thermophilic F1ATPase of
      a conserved site involved in iron binding and in oxidative inactivation, in which
      iron exhibits similar redox properties. On the other hand, at variance with
      thermophilic F1ATPase, the mitochondrial enzyme has the possibility of
      maintaining one equivalent of Fe(II) in its peculiar ATP-dependent site, besides
      one equivalent of Fe(III) in the conserved nucleotide-independent site. In this
      case mitochondrial F1ATPase undergoes a higher inactivation (75%) upon exposure
      to H2O2. Under all conditions the inactivation is significantly prevented by PBN
      and DMSO but not by Cu, Zn superoxide dismutase, thus suggesting the formation of
      OH radicals as mediators of the oxidative damage. No dityrosines, carbonyls or
      oxidized thiols are formed. In addition, in any cases no protein fragmentation or
      aggregation is observed upon the treatment with H2O2.

PMID- 9645399
TI  - Comments on a commentary: statistical evaluation of split mouth caries trials.
AB  - When results of split mouth caries trials are reported, the most frequently used
      outcome measures are "effectiveness" and "net gain". In a recent review by
      Riordan & FitzGerald (Community Dent Oral Epidemiol 1994;22:192-7) of the
      statistical analysis of data from such trials, the close connection between
      effectiveness and the traditional epidemiological outcome measure, relative risk,
      was pointed out and the latter measure was recommended. The confidence intervals
      for these parameters were, however, incorrect. This note provides valid
      confidence intervals for net gain, effectiveness and relative risk based on data
      from split mouth trials and presents examples of the calculations.

PMID- 9645400
TI  - Design and analysis issues in split mouth clinical trials.

PMID- 9645401
TI  - Impact of diagnostic criteria on the prevalence of dental caries in Norwegian
      children aged 5, 12 and 18 years.
AB  - The study aimed to investigate caries prevalence in children using a severity
      grading diagnostic system, and to evaluate the influence of different diagnostic
      thresholds on the caries data. A group of 513 children, aged 5, 12 and 18 years,
      were examined clinically, and with available bitewing radiographs, by four
      calibrated examiners. The inter- and intra-examiner reliability, assessed by a
      weighted kappa, varied between 0.80 and 0.95. The mean dmft/DMFT values were 3.8,
      5.8 and 11.0 for the three age groups respectively, and the corresponding
      dmfs/DMFS values were 5.4, 9.9 and 22.6. The d/D-component constituted the major
      part of the dmf/DMF index in all age groups, and enamel lesions accounted for
      59%, 89% and 86% of the d/D-component in the three age groups respectively. It is
      concluded that enamel or initial caries lesions contributed substantially to the
      total caries prevalence, illustrating the importance of using diagnostic criteria
      that include all stages of clinical caries if a total picture of the caries
      situation is needed.

PMID- 9645402
TI  - Satisfaction with dental care among elderly Finnish men.
AB  - To study satisfaction with dental care among elderly Finnish men and to estimate
      the role of different factors affecting it, a questionnaire was sent to a
      systematic sample of 2043 elderly Finnish men (mean age 73 years). Acceptably
      filled-out questionnaires were returned by 1561, a participation rate of 76.4%.
      The questionnaire included 44 questions concerning dental and denture services
      and a modified 14-item Dental Satisfaction Questionnaire. The subjects were asked
      to express how strongly they agreed or disagreed with each of the 14 statements.
      These were later transformed and recoded to indicate level of satisfaction from
      +2 (very satisfied) to -2 (very dissatisfied). Overall satisfaction was estimated
      by summing up all the 14 scores. Dentate subjects were significantly (P<0.01)
      more satisfied than the edentulous. Subjects were least satisfied with dental
      care fees and most satisfied with accessibility and availability of services.
      Dentate subjects viewed almost all 14 items significantly more favorably than did
      the edentulous. Economics was seen to have a strong influence on dissatisfaction
      with dental care fees, which was related to income level. Maintaining the
      remaining dentition and supporting the dentition with fixed or removable dentures
      seem to be the means to increase satisfaction among the dentate. The benefits of
      belonging to a clinic's recall system should be explained thoroughly to the
      elderly.

PMID- 9645403
TI  - Tooth and tooth surface survival rates in birth cohorts from 1965, 1970, 1975,
      and 1980 in Lahti, Finland.
AB  - Differences in the tooth and tooth surface survival rates between four cohorts
      born in 1965, 1970, 1975, and 1980 were analysed in a historical cohort study
      including data on the permanent teeth of children aged 5-7 years at baseline and
      19 years at the end of the study. A statistically significant reduction in caries
      occurrence in fissured surfaces in the three oldest cohorts was seen during the 3
      years after the eruption of the teeth. Caries occurrence in the cohorts born in
      1975 and 1980 did not differ from each other. The occurrence of caries in smooth
      surfaces was low in all age cohorts. Therefore, despite a systematic decrease in
      caries occurrence towards the younger cohorts, no significant differences were
      found between the cohorts in smooth surface decay. After the 3 first posteruptive
      years, practically no differences in survival rates between the cohorts were
      observed. In the two youngest cohorts, the figures during the 3 first years after
      eruption did not differ from the figures for the later years. Throughout the
      study, caries occurrence was symmetric and no gender differences were observed.
      No postponement of decay was found by the end of the follow-up time.

PMID- 9645404
TI  - Does dental service utilization drop during economic recession? The example of
      Finland, 1991-94.
AB  - After enjoying rapid economic growth in the 1980s, Finland suffered a deep
      economic recession that began in 1990. It has been claimed that recession and
      uneven subsidies influence the use of dental services negatively. Finnish adults
      born after 1956 and world war veterans are entitled to subsidized dental care
      either in the Public Dental Service (PDS) or in the private sector. Other adults
      pay their treatment costs. OBJECTIVES: The purpose of this paper is to determine
      whether the economic recession in Finland during the early 1990s affected the use
      of dental services. METHODS: The data were collected by the National Research and
      Development Centre for Welfare and Health using a method called CATI (Computer
      Assisted Telephone Interview). The target population was non-institutionalized
      persons aged 25-79 years. RESULTS: About one-third of those interviewed had
      visited a dentist during the previous 6 months and this proportion was stable
      during the years studied. Number of teeth, length of education, income and sex
      had the highest predictive values for use of dental services as analyzed by
      multiple logistic regression. Two-thirds had visited a private practitioner, one
      third a PDS clinic and a small percentage some other dentist or denturist.
      CONCLUSIONS: The results showed that the dental service utilization by Finns was
      stable during this period of economic downturn and only minor changes occurred in
      the mean number of visits. The most prominent change was seen in the youngest age
      group, among whom dental utilization decreased by almost 10%. The study indicated
      that subsidies do not strongly affect dental utilization today.

PMID- 9645405
TI  - Approximal caries and sugar consumption in Icelandic teenagers.
AB  - The aim of this study, conducted in 1994, was to examine the association between
      approximal caries and sugar consumption in teenagers residing in three fluoride
      deficient areas in Iceland while controlling for a number of behavioral,
      residential and microbiological factors. One hundred and fifty subjects (mean age
      14 years) selected from the Icelandic Nutritional Survey (INS) were examined
      radiographically and they completed questionnaires about sugar consumption
      frequency. Total grams of sugar intake were obtained from the INS for each
      subject. Caries experience on approximal surfaces, diagnosed from radiographs,
      was used as the dependent variable in the analyses. Altogether 45.2% of subjects
      were caries free on approximal surfaces. The overall sample was found to have a
      mean DFS on approximal surfaces of 2.73 (s=4.36) per subject. Average daily total
      sugar intake was 170 g per subject and the mean number of sugar-eating occasions
      between meals was 5.32 (s=6.29) per subject. The regression model indicated that
      the frequency of between-meal sugar consumption was associated with approximal
      caries, with frequency of candy consumption being the most important of the sugar
      variables. In multivariate analysis, no relationship was found between dental
      caries and total daily intake of sugar, although a significant relationship
      between total sugar consumption and presence of caries was seen in bivariate
      analysis. Between-meal consumption of sugar remains a risk factor for the
      occurrence of dental caries, especially in populations with moderate-to-high
      levels of dental caries experience.

PMID- 9645406
TI  - A practice-based study on stepwise excavation of deep carious lesions in
      permanent teeth: a 1-year follow-up study.
AB  - This study reports results from a practice-based study in which deep carious
      lesions were treated by general dental practitioners using stepwise excavation.
      The material comprised 94 teeth with deep carious lesions which the clinicians
      considered would result in pulp perforation if treated by a single and terminal
      excavation. At the first visit excavation of the peripheral dentine was
      completed. The outermost part of the central and necrotic dentine was gently
      removed with a sharp excavator. Standardized assessments of the dentine colour
      and consistency were made before application of a calcium hydroxide-containing
      base material and temporary filling. The final excavation was completed after a
      treatment interval ranging from 2 to 19 months, with a median of 6 months.
      Reassessments of the dentine colour and consistency were made before complete
      removal of demineralized dentine. The central dentine was significantly browner
      and less softened after the sealing period. After removal of the dark-brownish
      dentine during the final excavation, the colour and consistency of the exposed
      central dentine was found to resemble that of the completely excavated peripheral
      dentine. Only five cases resulted in pulp perforation during the final
      excavation. The high success rate of teeth surviving the final treatment without
      pulp exposure after 1 year of observation shows that it was possible for dentists
      in general practice to administer and manage the treatment of deep carious
      lesions, a process which may prolong tooth survival compared with conventional
      endodontic techniques.

PMID- 9645407
TI  - Stability of dental health behavior: a 3-year prospective cohort study of 15-, 16
      and 18-year-old Norwegian adolescents.
AB  - There is a need for a descriptive epidemiology of patterns of dental health
      behavior through adolescence. OBJECTIVES: The purpose of this study was to assess
      the tracking (degree of stability) of several categories of self-reported dental
      health behavior in adolescence over a 3-year period. METHODS: In 1992, a
      representative sample of 970 15-year-old adolescents of Hordaland county, Norway,
      completed questionnaires under supervision at school. Postal follow-up studies 1
      and 3 years later provided 709 and 781 answers, respectively. The present
      analyses included 581 adolescents who participated on all three occasions and 670
      adolescents who replied in 1992 and 1995. Paired sample t-tests, cross
      tabulations and Pearson's correlation coefficients were used to assess stability.
      For use in the cross-tabulations all variables were transformed into binary
      categories (active and inactive). RESULTS: A substantial proportion of
      adolescents remained consistently in the same behavioral category for all 3
      survey years. Toothbrushing (80%) and use of dental floss (64%) were the most
      stable activities, while consumption of sugared mineral water (53%), intake of
      chocolate/sweets (52%) and use of F-rinse (54%) were less stable. However,
      Pearson's correlations between corresponding behaviors assessed in 1992 and 1995
      were moderate and varied from 0.59 (toothbrushing) to 0.22 (F-rinse) (P<0.001).
      CONCLUSION: The results do not conclusively indicate a pattern of tracking. The
      tendency is, however, clear enough to support the assumption that dental health
      behavior continues during adolescence into adulthood.

PMID- 9645408
TI  - Satisfaction as a determinant of compliance.
AB  - In this study the relation between satisfaction and compliance is examined in
      terms of specificity and predictive value. Satisfaction is assumed to be a
      determinant of compliance, especially if both concepts are measured at the same
      level of specificity (i.e., a dental level). A total of 176 subjects reported
      their satisfaction with dental visits and the dental practice, their dental
      compliance and their general tendency to comply. The results show a relation
      between satisfaction and compliance and that compliance can be predicted by
      satisfaction. Surprisingly, the relation between dental satisfaction and general
      compliance is stronger than the relation between dental satisfaction and dental
      compliance. This finding can be explained by the possible relation between
      different levels of compliance and the complexity of the concept dental
      compliance.

PMID- 9645409
TI  - Treatment of amyloidosis and the rheumatologist. State of the art and
      perspectives for the future.
AB  - The rheumatologist must be prepared to face diagnostic and therapeutic problems
      related to different categories of amyloidosis. This applies to the systemic AA
      amyloidosis that complicates chronic inflammatory arthropathies like adult and
      juvenile rheumatoid arthritis, causing nephropathy and various internal
      manifestations. Other types of amyloidosis are essential because they may
      localize to structures of the locomotor system and cause rheumatic complaints. At
      present, there is no cure for amyloidosis. But adequate and especially early
      therapeutic intervention is helpful in many cases. This review focuses on
      treatment of the categories of amyloidosis which are most relevant to the
      rheumatologist. In addition to treatments that are available today, more
      effective therapeutic modalities which hopefully will be available in the near
      future are also reviewed.

PMID- 9645410
TI  - Allergic disorders in primary Sjogren's syndrome.
AB  - Allergic disorders have been described in a variety of connective tissue
      disorders. Although an association between allergy and primary Sjogren's syndrome
      has been suggested, it has not been well documented. The purpose of this study
      was to analyze the prevalence of several types of allergic disorders in a cohort
      of primary Sjogren's syndrome patients. The presence of an allergic disorder was
      evaluated by a specific questionnaire in 65 randomly selected primary Sjogren's
      syndrome patients and was compared to control groups of 67 rheumatoid arthritis
      patients, 53 patients with rheumatoid arthritis and sicca symptoms, and 31
      patients with osteoarthritis. At least one type of allergic manifestation was
      reported by 42 of the 65 Sjogren's syndrome patients (65%). This rate was
      significantly higher than each of the three control groups (p < 0.01). Only drug
      allergy and skin contact allergy were found to be more prevalent in Sjogren's
      syndrome patients than in the control groups (p< 0.05). Allergic reactions were
      more common in Sjogren's syndrome patients who were anti-Ro positive (p < 0.05).
      As drug and skin contact allergies are a frequent finding in Sjogren's syndrome
      patients, obtaining a careful history is needed before prescribing drugs in these
      patients.

PMID- 9645411
TI  - Laboratory screening for side effects of disease modifying antirheumatic drugs in
      daily rheumatological practice.
AB  - To observe the actual laboratory screening for side effects of disease modifying
      antirheumatic drugs (DMARDs) in daily rheumatological practice, a retrospective
      multi-center cohort study was performed on the laboratory tests in DMARD treated
      rheumatoid arthritis (RA) patients. RA patients were investigated by chart review
      if they started with a DMARD (cohort 1) or were treated with a DMARD for at least
      one year (cohort 2). Hematological, hepatic, and renal tests were collected. In
      cohort 1 and 2, 513 and 1209 patients were included, respectively. A fairly
      outlined screening profile was observed for each DMARD studied. Except for
      antimalarials, the testing frequency decreased with time in cohort 1. For all
      DMARDs the testing frequency in cohort 1 was higher than in cohort 2. In general,
      rheumatologists requested laboratory tests less frequently than is
      internationally recommended. This discrepancy raises questions about the relation
      between the efficacy and costs of laboratory screening for side effects of DMARDs
      in patients with RA.

PMID- 9645412
TI  - Zopiclone as night medication in rheumatoid arthritis.
AB  - Sleep disturbances and related daytime complaints are frequent in rheumatoid
      arthritis (RA). The aim of the current study was therefore to evaluate the effect
      of a newer hypnotic on sleep structure and clinical parameters in RA. Forty
      outpatients were randomized to a two week treatment regimen with either 7.5 mg
      zopiclone or placebo at bedtime. Clinical examinations were performed before and
      after treatment and the degree of pain, fatigue, sleepiness, morning stiffness,
      and activities of daily living were assessed. Two sleep questionnaires were also
      completed weekly. Polysomnography was performed before the study and after 14
      days of treatment. Recordings were evaluated using conventional sleep scoring as
      well as frequency analysis of the electroencephalography (EEG). Patients in the
      zopiclone group had subjective improvement of sleep, but otherwise no differences
      in pain score or the other clinical parameters were found. Conventional sleep
      assessments showed only minor changes during treatment, but frequency analysis
      demonstrated a shift from the lower towards the higher EEG frequencies in the
      active treatment group. Although the modulation of the EEG can represent a non
      specific pharmacologic epiphenomenon, it might also reflect a disturbance of
      sleep microstructure. In conclusion, treatment with zopiclone may be of value for
      subjective sleep complaints in selected patients with RA, but it is doubtful
      whether hypnotics improve daytime symptoms in this patient group.

PMID- 9645413
TI  - Low incidence of osteoporosis in a two year follow-up of early community based
      patients with rheumatoid arthritis.
AB  - 52 patients with early rheumatoid arthritis (RA) were followed with regular
      measurements of bone mineral density (BMD) and serum markers of type I collagen
      metabolism in order to determine whether they develop osteoporosis during the
      first two years of the disease course and if the changes in type I collagen
      metabolites reflect the alterations in BMD. The mean percentage BMD change over
      the first year of follow-up was -0.91 for lumbar spine (LS) and -0.76 for femoral
      neck (FN); the corresponding figures from 0 to 24 months was -1.3 and -0.8,
      respectively. During the follow-up, only five patients developed osteoporosis by
      the Z-score definition (<-1). If defined by T-score (<-2.5) none of the patients
      developed osteoporosis. The BMD change correlated neither with the clinical
      parameters of disease activity nor with the markers of collagen metabolism.
      However, the BMD change in FN was associated with the cumulative corticosteroid
      dose (r=-0.31, p <0.05, 95% CI -0.54 to -0.04). Reasons for the lack of
      accelerated bone loss in our series are open to various interpretations. This
      series was community based and most of the patients had mild RA. The patients
      were also actively treated and their physical function did not deteriorate.

PMID- 9645414
TI  - Destruction and arthroplasties of the metatarsophalangeal joints in seropositive
      rheumatoid arthritis. A 20-year follow-up study.
AB  - Destruction and arthroplasties of the metatarsophalangeal (MTP)joints and
      interphalangeal (IP) joint of the big toe were evaluated in 103 seropositive
      rheumatoid arthritis (RA) patients in a prospective follow-up study at onset and
      at 1, 3, 8, 15, and 20 years from entry. A total of 83 patients attended the 15
      year follow-up and 68 attended the 20-year follow-up. Data on the forefoot
      synovectomies and reconstructions performed were obtained from patient documents
      and radiographs. The radiographs were assigned by the Larsen method; in the end
      point analysis the last or preoperative radiograph was used. Erosions of Larsen
      grade > or =2 were present in 6%/ of the investigated 1236 joints at onset and
      after 20 years in 62%, respectively. At the end point, 24% of the joints were
      severely damaged (Larsen grade 4-5). The MTP I and IP joints showed the lowest
      grade of destruction during follow-up, and MTP V the worst destruction.
      Synovectomies were performed in 24 MTP joints; a total of 75% of these joints
      were later resected. MTP II-V head resections were performed in 21% and the
      Keller procedure in 12% of the MTP I joints. Erosive changes occur early in the
      MTP joints, and their grade of destruction is high; therefore they should be
      included in radiographic criteria and scores. MTP synovectomies are insufficient
      treatments for RA without concomitant immunosuppression of the disease.

PMID- 9645415
TI  - Bone metabolism in patients with systemic lupus erythematosus. Effect of disease
      activity and glucocorticoid treatment.
AB  - The bone metabolism in patients with systemic lupus erythematosus (SLE) has
      previously been examined, but the results are conflicting. In the present study
      the bone mineral density (BMD) of the axial and the appendicular skeleton was
      examined by means of dual energy x-ray absorptiometry. The bone turnover was
      evaluated by means of biochemical markers in serum and urine in a prospective
      cohort consisting of 36 female and male SLE patients. Repeated measurements of
      BMD were performed for up to two years. The BMD was decreased in the hand and in
      the femoral neck but normal in the spine and in the distal forearm. A weak
      correlation was found between the BMD of the femoral neck and the total
      consumption of glucocorticoids. Apart from this finding the BMD was uninfluenced
      by treatment with glucocorticoids and cyclophosphamide. No significant changes of
      BMD were found during the follow-up period. The serum concentration of the
      carboxyterminal cross-linked telopeptide of type I collagen was increased in
      almost all patients, but no other biochemical markers of bone metabolism were
      abnormal.

PMID- 9645416
TI  - Skeletal muscle immune deposits in systemic lupus erythematosus. Correlation with
      histologic changes, autoantibodies, and clinical involvement.
AB  - Skeletal muscle biopsy and autopsy samples of 132 SLE patients were studied by
      immunofluorescence and light microscopic techniques. Immune deposits were
      compared to histologic abnormalities and clinical and serologic findings. Immune
      deposits with a mainly granular pattern were observed at different locations in
      49 patients (37%). They correlated significantly (p<0.001) with inflammatory
      myopathy, demonstrated in 33(25%), with noninflammatory myopathy which occurred
      in 38 (29%) vasculitis, observed in 13(10%), and with noninflammatory
      vasculopathy which was noted in 10 patients (8%). The correlation of muscle
      immune deposits with anti-DNA antibodies was significant at p= 0.016. Anti-Sm and
      anti-U1 RNP antibodies were associated significantly with the intensity of immune
      deposits. Furthermore, a correlation of immune deposits with increased creatine
      phosphokinase and myopathic electromyogram, but not with evidence of clinical
      involvement, was shown. A key pathogenetic role of immune deposits in the
      development of skeletal muscle histologic abnormalities in SLE was demonstrated.

PMID- 9645417
TI  - Expression of the mucosal lymphocyte integrin alphaEbeta7 and its ligand E
      cadherin in salivary glands of patients with Sjogren's syndrome.
AB  - The expression of the mucosal lymphocyte integrin alphaEbeta7 and its ligand E
      cadherin was analyzed in sialadenitic lesions of patients with Sjogren's syndrome
      in order to assess the potential interactions between the mucosal and the
      systemic immunological compartments. Immunohistochemical evaluation of the
      inflammatory infiltrates in the salivary gland tissues in Sjogren's syndrome
      patients revealed presence of alphaEbeta7-integrin-expressing lymphocytes, in 18
      of 20 biopsies examined. The ligand for alphaEbeta7, E-cadherin was also found in
      18 of 20 salivary gland biopsies analysed. These results suggest homing of
      lymphocytes derived from the gut epithelium through the blood stream to inflamed
      salivary gland tissue followed by in situ interaction with E-cadherin expressing
      cells, the ligand for alphaEbeta7 expressing T lymphocytes.

PMID- 9645418
TI  - Decreased Th1-like and increased Th2-like cells in systemic lupus erythematosus.
AB  - The proportion of the lymphocytes which produce the cytokines corresponding to
      murine T helper- (Th1) or Th2 cells was studied using flow cytometry in systemic
      lupus erythematosus (SLE). When the peripheral mononuclear cells were stimulated
      with phorbol myristate acetate and ionomycin in the presence of monensin, which
      blocks the secretion of cytokines, the positive rates for the cytoplasmic IL-2
      and IFN-gamma were lower and those for the cytoplasmic IL-4 and IL-10 were higher
      in SLE than in normal subjects. When the cells were cultured with monensin alone,
      the positive rates for these 4 cytokines were slightly increased in SLE. These
      data suggest that the mononuclear cells are already activated in vivo and a
      deviation of the proportion of the Th cells to the Th2-like ones might be
      associated with the polyclonal B cell activation seen in SLE.

PMID- 9645419
TI  - TAP2 alleles in inflammatory arthritis.
AB  - Sixty patients with reactive arthritis (ReA) and 40 with rheumatoid arthritis
      (RA), were typed for H LA-B27 and class II antigens DR and DQ, and studied for
      TAP2 gene polymorphism in comparison with 60 healthy controls. TAP2 polymorphisms
      at positions 379, 565, 665, and 687 were analyzed using amplification refractory
      system-based PCR and polymorphisms at positions 386 and 651 using oligonucleotide
      hybridization. The frequency of the TAP2A/A genotype was 30%(12/40) in RA, in
      contrast to 13% (8/60) in the controls. This genotype was further associated with
      DRB1*04 positive RA (10/24, 42%, P=0.01), as well as the TAP2A allele (31/48,
      65%, P =0.012). Thr/Thr dimorphism at TAP2 position 665 (24/40, 60%, P=0.024) and
      Stop/Stop dimorphism at TAP2 position 687 (24/40, 60%, P=0.024) were found to be
      increased in RA patients as compared to controls. When TAP2I/J polymorphism was
      studied, TAP2J positivity was found associated with the HLA-B27DR4-DQB1*0301
      haplotype in ReA patients. 9/12 of these were positive as compared to 20/60 in
      random controls (P=0.010). Polymorphisms of the TAP2 gene were found to be
      associated with subgroups of RA and ReA patients with disease associated markers
      (e.g. TAP2A in DRB1*04 positive RA, or TAP2J in HLA-B27-DRB1*04-DQB1*0301
      positive ReA). These may thus serve as additional markers of specific haplotypes
      associated with susceptibility to inflammatory arthritis.

PMID- 9645420
TI  - Churg-Strauss syndrome presenting with pulmonary capillaritis and diffuse
      alveolar hemorrhage.
AB  - Churg-Strauss syndrome (CSS) is a rare disorder characterized by the
      histopathological triad of systemic necrotizing vasculitis, extravascular
      granuloma, and eosinophilic infiltrate, occurring in individuals with asthma or a
      history of allergy. We report a case of CSS with rare presentation of diffuse
      pulmonary hemorrhage. A transbronchial lung biopsy showed necrotizing vasculitis,
      pulmonary capillaritis, and prominent eosinophilic infiltrate. At autopsy,
      necrotizing granuloma and diffuse alveolar hemorrhage were found in the lungs.
      Laboratory data showed hypereosinophilia, disseminated intravascular
      coagulopathy, and positive anti-proteinase 3 antineutrophil cytoplasmic antibody
      (ANCA). This case emphasize that CSS should be considered in the differential
      diagnosis of ANCA-positive vasculitis with diffuse alveolar hemorrhage.

PMID- 9645421
TI  - Henoch-Schoenlein purpura and acute interstitial nephritis after intravenous
      vancomycin administration in a patient with a staphylococcal infection.
AB  - We describe a case of Henoch-Schoenlein purpura, associated with oliguric acute
      renal failure due to acute interstitial nephritis histologically proven, in a
      patient with a staphylococcal chest infection. The clinical syndrome appeared
      twice after vancomycin administration and yielded on the withdrawal of the drug.
      As pathogenetic mechanism we propose an anaphylactoid reaction either to
      vancomycin or to a staphylococcal glycoprotein released after breakdown of the
      microbial cells caused by vancomycin.

PMID- 9645422
TI  - Peripheral beta-endorphin in rheumatoid arthritis.

PMID- 9645423
TI  - Cricoarytenoiditis in systemic lupus erythematosus.

PMID- 9645424
TI  - Cyclin-specific START events and the G1-phase specificity of arrest by mating
      factor in budding yeast.
AB  - The START cell cycle transition in the budding yeast Saccharomyces cerevisiae is
      catalyzed by the Cdc28 cyclin-dependent kinase associated with Cln-type cyclins.
      Since ectopic expression of the B-type cyclin CLB5 can efficiently rescue the
      inviability that results from CLN depletion, we tested the specificity of the CLN
      and CLB classes of cyclins for promoting START-associated events. Several aspects
      of the regulation of the mating factor response were compared for cells in which
      START activity was provided by either Cln-cyclins or Clb5. Unlike Cln1 and Cln2,
      high level expression of Clb5 was unable to repress the activity of the mating
      factor response pathway at START. Downregulation of Far1 protein at START is
      normal in cln- GAL1::CLB5 cells. Even though the Clb5-Cdc28 kinase activity in
      cln- GAL1::CLB5 cells is not downregulated in response to mating factor, cells
      arrest in the first cycle after addition of mating factor with a similar
      sensitivity as wild-type cells. However, whereas wild-type cells treated with
      mating factor arrest specifically in G1 phase as unbudded cells with unreplicated
      DNA (pre-START), most cln- GAL1::CLB5 cells arrest as budded post-START cells
      with replicated DNA. Our findings demonstrate the ability of post-START cells to
      arrest in response to mating factor and provide novel evidence for mechanisms
      that contribute to restrict mating factor-induced arrest in wild-type cells to
      the G1 phase of the cell cycle.

PMID- 9645425
TI  - Genes for the ribosomal S4 protein encoded in higher plant mitochondria are
      transcribed, edited, and translated.
AB  - Here we describe the structure and expression of the mitochondrial gene that
      encodes the S4 subunit of the mitochondrial ribosome (rps4) in two higher plants,
      rapeseed and rice. The ORFs of rapeseed and rice rps4 genes are 362 and 352
      codons long, respectively, and their corresponding transcripts are edited (C-to-U
      conversions) in 19 and 15 positions, respectively. The amino acid sequences
      deduced from the sequences of the two rps4 genes are 78.1% identical to each
      other and show about 50% identity to the liverwort (Marchantia polymorpha)
      mitochondrial RPS4 polypeptide. Both higher plant mitochondrial genes have an
      inserted sequence (of 137 and 141 codons for rapeseed and rice, respectively)
      relative to the liverwort rps4 gene. In rice rps4, the 3' portion of the inserted
      sequence can potentially form two stem-loop structures that resemble two domains
      characteristic of group II introns, i.e., domains V and VI. However, RT-PCR
      analysis showed that these sequences were not spliced out during maturation of
      the rps4 transcripts. Antibodies specific for the plant RPS4 proteins were
      prepared. Protein blot analysis revealed that RPS4 polypeptides are present in
      both rapeseed and rice mitochondria, whose sizes are in agreement with the
      molecular weights calculated from the non-spliced sequences. The rps4 genes and
      RPS4 polypeptides have been also identified in the mitochondria of wheat, maize,
      soybean, and turnip by Southern and Western analyses, respectively.

PMID- 9645426
TI  - Characterization of a 7S globulin-deficient mutant of soybean (Glycine max (L.)
      Merrill).
AB  - We attempted to characterize a soybean mutant lacking the 7S globulin (beta
      conglycinin) subunits, alpha, alpha' and beta. The results of Southern and
      northern blot analyses indicated that the deficiency is not caused by a lack of,
      or structural defects in, the 7S globulin subunit genes, but rather arises at the
      mRNA level. Despite the independent inheritance of the two loci containing the
      alpha-and alpha'-subunit genes and the organization of the multi-gene families
      encoding these subunits and the beta-subunit, a single recessive gene controls
      the null trait of the mutant. This, taken together with the above results, leads
      to the assumption that the mutant gene encodes a common factor that regulates the
      7S globulin subunit genes. Transient expression of glucuronidase from the
      promoters of the alpha'- and beta-subunit genes was detected in the mutant
      cotyledons. The results of gel mobility shift assays using the 5'-flanking
      regions of the alpha'- and beta-subunit genes failed to detect a deficiency of
      nuclear factors interacting with these regions. We propose that a seed-specific
      mechanism of expression of 7S globulin genes might be involved in chromatin
      organization, and that such an organization might not work normally in the
      mutant. The possibility that transcript stability is lowered in the mutant is not
      excluded.

PMID- 9645427
TI  - Expression of the yeast BFR2 gene is regulated at the transcriptional level and
      through degradation of its product.
AB  - The essential Saccharomyces cerevisiae gene BFR2 has been isolated as a high-copy
      suppressor of the growth defects induced by Brefeldin A, a drug that disrupts the
      Golgi apparatus and its protein influx. Furthermore, BFR2 has been found to
      display genetic interactions with four mutations affecting protein transport to
      the Golgi apparatus. Here we show that the level of BFR2 mRNA rapidly increased
      over fivefold in response to cold shock, and over threefold following nutrient
      replenishment by dilution of cells from exhausted to fresh minimal medium. During
      subsequent growth, the transcript level returned to its basal values, except for
      a transient drop toward the end of the exponential phase. The early burst of
      transcription was not caused by toxic compounds in the fresh medium, or by
      synchrony among cells that had simultaneously entered their first cell cycle. The
      BFR2 gene product (Bfr2p) was synthesized following the early burst of mRNA, and
      was no longer produced when the mRNA was back to basal level. Bfr2p was finally
      degraded after growth became limited, and reached undetectable levels in
      exhausted medium. Under steady-state conditions of lengthened exponential phase,
      the intracellular level of Bfr2p remained constant. This peculiar pattern of gene
      expression suggests that Bfr2p is essential for mass growth or cell
      proliferation, whereas it is either toxic or not required during nutrient-limited
      growth.

PMID- 9645428
TI  - Genetic rearrangements in the pathogenicity locus of Clostridium difficile strain
      8864--implications for transcription, expression and enzymatic activity of toxins
      A and B.
AB  - The pathogenicity locus (PaLoc) of Clostridium difficile isolate 8864 was
      investigated to locate genetic rearrangements that would explain the exceptional
      pathogenicity of this particular isolate. Two major changes were defined: an
      insertion of 1.1 kb between the two genes tcdA and tcdE, coding for the
      enterotoxin and an accessory protein of unknown function, respectively, and a
      deletion of 5.9 kb encompassing the 3' ends of tcdA and tcdC. Transcription of
      the tcdA-E genes is severely affected by both rearrangements, explaining the
      demonstrated complete lack of TcdA polypeptide. We present a model of coordinate,
      growth-related transcription of the tcdA-E genes that confirms our previous
      findings in strain 10463. Recombinant TcdA-8864 had UDP-glucose
      glucosyltransferase activity, proving that the N-terminal 698 amino acids of the
      polypeptide represent the catalytic domain. However, this truncated TcdA molecule
      lacks a ligand and translocation domain. To assess the catalytic domain of TcdB
      8864, the sequence of the 5' end of its gene was determined. TcdB-8864 shows high
      homology to TcdB-1470 but lower homology to TcdB-10463 within this domain. This
      fits well with the altered glucosylation specificity of TcdB-8864 (Rac1, Rap2 and
      Ra1). Having defined the variations of transcription, expression and enzymatic
      activity of toxins A and B, implications for the pathogenic potential of strain
      8864 are discussed.

PMID- 9645429
TI  - A single human cell expresses all messenger ribonucleic acids: the arrow of time
      in a cell.
AB  - Expression of 25 mRNAs in a single human lymphocyte was investigated using the
      reverse transcription nested polymerase chain reaction (RT nested PCR) method.
      Proteins corresponding to the mRNA investigated were mucin antigen, melanoma
      antigen, pregnancy-specific beta-1 glycoprotein 4, phenylethanolamine-N-methyl
      transferase, beta B3-crystallin, homeobox 4A, interleukin 2, cluster of
      differentiation 8, progesterone receptor, parathyroid hormone, gastrin,
      cholecystokinin/pancreozymin, glucagon, insulin, enkephalin, thyroid stimulating
      hormone, adrenocorticotropic hormone, synapsin I, immunoglobulin (Ig)M, IgD,
      IgG1, IgG3, IgE, IgA, and T cell receptor alpha. All mRNAs were detected in
      single lymphocytes of two individuals, without exception. In addition,
      transcripts of IgM, IgD, IgG1, IgG3, IgE, IgA, and the T cell receptor a gene
      were detected in single sperms. The results strongly suggest the possibility that
      all mRNAs may be expressed in a single human cell, of both somatic and germ
      lineage. Thus, cells can consume energy in vain to produce functionally
      meaningless gene transcripts. However, this basal or illegitimate transcription
      may be essential for the birth of living matter: the arrow of time in a cell.
      Moreover, the phenomenon implies the potential of using lymphocytes in place of
      inaccessible tissue for the diagnosis of genetic diseases.

PMID- 9645430
TI  - Genetic analysis of an essential cytoplasmic domain of Escherichia coli SecY
      based on resistance to Syd, a SecY-interacting protein.
AB  - We previously described a dominant negative secY-d1 allele in Escherichia coli,
      whose product interferes with protein export, presumably by sequestering SecE,
      the stabilizing partner of SecY. Syd is the product of a multicopy suppressor of
      the secY-d1 phenotype, and its overproduction preferentially stabilizes the wild
      type SecY protein. In contrast, overproduction of Syd is toxic to the secY24
      mutant, which shows a partial defect in SecY-SecE interaction. We isolated Syd
      resistant revertants from the secY24 mutant. Pseudo-reversions mapped to sites at
      or near the secY24 mutation site (Gly240-->Asp). The secY249 mutation (Ala249-
      >Val) intragenically suppressed Syd sensitivity, but not the temperature
      sensitive Sec phenotype of the secY24 mutation. The SecY249 mutant protein shows
      a reduced capacity to be stabilized by Syd, suggesting that the mutation weakens
      the SecY-Syd interaction. The other two mutations changed residue 240 (the site
      of the secY24 alteration) to Asn (secY245) or Ala (secY241) and restored the
      ability of the cell to export protein. Although the secY245 mutant retained some
      sensitivity to Syd overproduction, the secY241 mutant was completely Syd
      resistant. Furthermore, the secY241 mutation seemed to represent a "hyper
      reversion" with respect to the SecY-SecE interaction. Protein export in this
      mutant was no longer sensitive to SecY-d1. When the secY-d1 mutation was combined
      intragenically with secY241, the resulting double mutant gene (secY-d1-241)
      showed an increased ability to interfere with protein export. On the basis of our
      model for SecY-d1, these results suggest that the secY241 alteration enhances
      SecY-SecE interaction. These results indicate that residue 240 of SecY is crucial
      for the interaction between the cytosolic domains of SecY and SecE required for
      the establishment of the translocase complex.

PMID- 9645431
TI  - Characterization of ptxS, a Pseudomonas aeruginosa gene which interferes with the
      effect of the exotoxin A positive regulatory gene, ptxR.
AB  - The complicated process of exotoxin A production by Pseudomonas aeruginosa is
      controlled by several genes. We have recently described a toxA positive
      regulatory gene, ptxR. We also proposed the presence of another gene which is
      adjacent to ptxR and interferes with ptxR function on exotoxin A production. In
      the presence of a fragment that carries the putative gene, the enhancement in
      exotoxin A production by ptxR was reduced threefold. In this study, we describe
      the characterization of this gene. Nucleotide sequence analysis of the 2.1-kbp
      fragment at the 5' end of ptxR revealed the presence of an open reading frame
      designated ptxS (the gene next to ptxR) which encodes a 37.4-kDa protein. The
      gene ptxS is transcribed in the opposite orientation to ptxR from the other DNA
      strand. The deduced amino acid sequence of ptxS exhibited a strong homology to
      several proteins of the GalR-LacI family of repressors. A putative helix-turn
      helix DNA binding motif was identified at the amino-terminus region of PtxS. When
      PtxS was overexpressed in Escherichia coli using the T7 expression system, a
      single protein of 38-kDa molecular weight was detected. An isogenic mutant
      defective in ptxS was constructed in PAO1 using the gene replacement technique.
      The loss of ptxS resulted in a twofold increase in exotoxin A production compared
      to PAO1. The effect of ptxS on ptxR was examined using a ptxR-lacZ fusion. In the
      presence of ptxS, the level of beta-galactosidase activity produced by the ptxR
      lacZ fusion was significantly reduced. These results suggest that ptxS encodes a
      protein which negatively regulates ptxR expression in P. aeruginosa.

PMID- 9645432
TI  - Inheritance and usefulness of AFLP markers in channel catfish (Ictalurus
      punctatus), blue catfish (I. furcatus), and their F1, F2, and backcross hybrids.
AB  - Eight primer combinations were used to investigate the application of amplified
      fragment length polymorphism (AFLP) markers in catfish for genetic analysis.
      Intraspecific polymorphism was low among channel catfish or blue catfish strains.
      Interspecific AFLP polymorphism was high between the channel catfish and blue
      catfish. Each primer combination generated from 70 to more than 200 bands, of
      which 38.6 75.7% were polymorphic between channel catfish and blue catfish. On
      average, more than 20 polymorphic bands per primer combination were produced as
      quality markers suitable for genetic analysis. All AFLP markers were transmitted
      into channel catfish x blue catfish F1 hybrids, except rare markers that were
      heterozygous in the parents and therefore were segregating in F1 hybrids. The two
      reciprocal channel catfish x blue catfish F1 hybrids (channel catfish female x
      blue catfish male; blue catfish female x channel catfish male) produced identical
      AFLP profiles. The AFLP markers were inherited and segregated in expected
      Mendelian ratios. At two loci, E8-b9 and E8-b2, markers were found at
      significantly lower frequencies than expected with F2 and backcross hybrids which
      had been selected for increased growth rates. The reproducibility of AFLP was
      excellent. These characteristics of the catfish AFLP markers make them highly
      useful for genetic analysis of catfish, especially for construction of genetic
      linkage and quantitative trait loci maps, and for marker-assisted selection.

PMID- 9645433
TI  - HSF3, a new heat shock factor from Arabidopsis thaliana, derepresses the heat
      shock response and confers thermotolerance when overexpressed in transgenic
      plants.
AB  - Organisms synthesize heat shock proteins (HSPs) in response to sublethal heat
      stress and concomitantly acquire increased tolerance against a subsequent,
      otherwise lethal, heat shock. Heat shock factor (HSF) is essential for the
      transcription of many HSP genes. We report the isolation of two HSF genes, HSF3
      and HSF4, from an Arabidopsis cDNA library. Transgenic Arabidopsis plants were
      generated containing constructs that allow expression of HSF3 and HSF4 or the
      respective translational beta-glucuronidase (GUS) fusions. Overexpression of HSF3
      or HSF3-GUS, but not of HSF4 or HSF4-GUS, causes HSP synthesis at the non-heat
      shock temperature of 25 degrees C in transgenic Arabidopsis. In transgenic plants
      bearing HSF3/HSF3-GUS, transcription of several heat shock genes is derepressed.
      Electrophoretic mobility shift assays suggest that derepression of the heat shock
      response is mediated by HSF3/HSF3-GUS functioning as transcription factor.
      HSF3/HSF3-GUS-overexpressing Arabidopsis plants show an increase in basal
      thermotolerance, indicating the importance of HSFs and HSF-regulated genes as
      determinants of thermoprotective processes. Plants transgenic for HSF3/HSF3-GUS
      exhibit no other obvious phenotypic alterations. Derepression of HSF activity
      upon overexpression suggests the titration of a negative regulator of HSF3 or an
      intrinsic constitutive activity of HSF3. We assume that stable overexpression of
      HSFs may be applied to other organisms as a means of derepressing the heat shock
      response.

PMID- 9645434
TI  - Alteration of the largest subunit of RNA polymerase II and its effect on
      chromosome stability in Schizosaccharomyces pombe.
AB  - A mutation in the RNA polymerase II largest subunit (RpII LS) that is related to
      abnormal induction of sister chromatid exchange has previously been described the
      CHO-K1 cell mutant tsTM4. To elucidate the molecular basis of this effect we
      introduced the mutation into the homologous site in the Schizosaccharomyces pombe
      rpbl gene, which encodes RpII LS. Since the tsTM4 mutant exhibited a decrease in
      the rate of DNA synthesis in cells arrested in S phase at the nonpermissive
      temperature, we focussed on the study of growth, the cell cycle, and chromosome
      stability at various temperatures. First, we examined the effects of the mutation
      on haploid yeast cells. The mutant showed slower growth than the wild type, but
      cell growth was not arrested at the nonpermissive temperature. When growing cells
      were shifted to the nonpermissive temperature, an accumulation of cells in G1
      and/or G0 was observed. Tetrad analysis suggested that these phenotypes were
      associated with the mutation. In diploid cells, chromosome instability was
      detected by loss of intragenic complementation between two alleles of the ade6
      gene. An abnormal fraction of cells containing an intermediate DNA content was
      also observed by FACS analysis. The accumulation of this fraction may reflect the
      fact that a large number of cells are in S phase or have an abnormal DNA content
      as a result of chromosome instability. These observations demonstrate that the S.
      pombe rpb1 mutant exhibits a phenotype very similar to that of the CHO-K1 cell
      mutant tsTM4.

PMID- 9645435
TI  - Identification and characterisation of an RPD3 homologue from maize (Zea mays L.)
      that is able to complement an rpd3 null mutant of Saccharomyces cerevisiae.
AB  - In mammals, yeast and Drosophila, the histone deacetylase RPD3 proteins can alter
      the expression of genes involved in fundamental biological processes by affecting
      the degree of acetylation of histones and changing chromatin structure. Here we
      report the isolation of a cDNA sequence encoding an RPD3 homologue from maize,
      which is able to complement the phenotype of an rpd3 null mutant of the yeast
      Saccharomyces cerevisiae. The expression of the corresponding gene(s) was
      assessed in different maize tissues. The number of homologous loci was estimated
      by Southern hybridisation to be in the range of two to three, and the chromosomal
      location of one of these loci was determined. Phylogenetic analysis and tests for
      relative divergence rates, using related RPD3 sequences from different species,
      were performed, and suggest that different polymorphic forms of RPD3-like
      proteins that evolve at distinct rates are present in the species considered.

PMID- 9645436
TI  - Integration host factor affects the oxygen-regulated expression of photosynthesis
      genes in Rhodobacter capsulatus.
AB  - The puf and puc operons of Rhodobacter capsulatus, which encode pigment binding
      proteins, are regulated by oxygen tension. Strain IR4 which carries a point
      mutation in the himA gene for integration host factor (IHF) shows a delayed
      increase in the amount of photosynthetic complexes after reduction of oxygen
      tension when compared to the isogenic wild-type strain. This delay in the
      formation of photosynthetic complexes correlates with a delay in increasing the
      level of transcription of the puf and puc operons, whereas the transcription of
      the bchD genes is not affected by IHF. Several IHF binding sites can be
      identified upstream of the puf and puc transcriptional starts by in vitro
      footprint analysis. Our results suggest that IHF facilitates the binding of other
      trans-acting factors, e.g. RegA, which in turn stimulate transcription of the puf
      and puc genes under low oxygen tension.

PMID- 9645437
TI  - Analysis of the Ac promoter: structure and regulation.
AB  - The Ac-encoded transposase, a factor that is essential for the mobility of the Ac
      element, is expressed under the control of a promoter that lacks a conventional
      TATA box. The regulation of this promoter is poorly understood. We have analyzed
      Ac promoter structure and activity, both in vitro and in vivo, using transgenic
      tobacco plants and cell suspensions. A deletion analysis of the Ac 5' region
      showed that the minimal promoter is located within 70 bp of the major
      transcription initiation site (at position 334). The minimal promoter includes
      the sequence TAAGAAATA at position 294 303, i.e., about 30 nucleotides upstream
      from the transcription start site. This sequence binds specifically to the TATA
      binding protein (TBP), suggesting that it is functional as a TATA box. The
      regulation of the Ac promoter was studied throughout plant development. Levels of
      Ac mRNA were low in all tissues studied, with higher expression being observed in
      dividing cells. In order to test whether Ac promoter is regulated during the cell
      cycle, a tobacco cell suspension transformed with Ac, was grown synchronously. No
      differences were found in Ac mRNA levels between cells in S, G2, M, or G1 phases;
      however, expression was lower in the stationary phase. We conclude that Ac
      promoter is not cell-cycle regulated but is expressed at a higher level in
      dividing cells. The possible relationship between promoter features and the
      regulation of Ac element transposition is discussed.

PMID- 9645438
TI  - Genetic aspects of prostate cancer.
AB  - Despite its high incidence and mortality rate, the molecular mechanisms
      underlying the oncogenesis and progression of prostate cancer are still unclear.
      This review, based on recently published data, surveys the current state of
      knowledge of human prostate oncogenesis, dealing with genetic predisposition in
      familial clusters of prostate cancer, providing new information on the somatic
      genetic alterations, which have been approached in four ways (measurement of DNA
      content, cytogenetic analysis, in situ hybridization, and molecular analysis),
      and investigating the problems of androgen independence and intratumour
      heterogeneity in prostate tumours. Lastly, the potential clinical applications of
      the genetic alterations, which may become important in the near future, are
      addressed.

PMID- 9645439
TI  - Mitogen-activated protein kinases and apoptosis in PIN.
AB  - Mitogen-activated protein (MAP) kinases are key elements of the signalling
      systems needed to transduce different extracellular messages into cellular
      responses. At least three parallel MAP kinase pathways have been identified: one,
      stimulated by serum and growth factors to activate extracellular signal-regulated
      protein kinases (ERKs) by dual tyrosine and threonine phosphorylation, triggers
      cell proliferation or differentiation; the other two, induced by a variety of
      cellular stresses to activate c-jun N-terminal kinases (JNKs) and reactivating
      kinase (p38/RK), result in growth arrest and induction of apoptosis. Mitogen
      activated protein kinase phosphatases (MKPs) inactivate MAP kinases through
      dephosphorylation and, thus, can modulate the MAP kinase pathways. Expression of
      JNK-1, ERK-1, p38/RK and MKP-1 proteins was investigated by immunohistochemistry
      and expression of MKP-1 mRNA by in situ hybridisation in 50 cases of high-grade
      prostatic intraepithelial neoplasia (PIN), thought to represent the precursor of
      prostate cancer. The frequency of apoptotic cells was also determined in these
      cases. Overexpression of the three MAP kinases and MKP-1 mRNA was found in all
      cases of high-grade PIN compared with normal prostate. Immunoreactivity for MKP-1
      protein was found to be as intense as in normal glands in 30% and weaker in 56%
      of the PIN cases. Fourteen per cent of PIN cases did not stain with MKP-1
      antibody. The proportion of apoptosis was significantly higher (P < 0.008) in PIN
      lesions that did not express MKP-1 protein than in those that did. These results
      are consistent with our previous demonstration of preferential inhibition of the
      apoptosis-related kinases by MKP-1 and further support the contention that MKP-1,
      even in PIN, may shift the balance existing between cell proliferation and death.
      When expressed, it may inhibiting those pathways that lead to apoptosis.

PMID- 9645440
TI  - Apoptosis in human colorectal tumours: ultrastructure and quantitative studies on
      tissue localization and association with bak expression.
AB  - Apoptotic cell death in human tumours has been demonstrated by electron and light
      microscopy. In adenomas, fragmented and apoptotic nuclei and signs of
      phagocytosis have been observed close to the basement membrane. In carcinomas the
      characteristic structures were apoptotic bodies with small fragments of
      chromatin. DNA fragmentation was shown by in situ end-labelling. Quantitative
      assessment of apoptosis and proliferation revealed a high apoptotic index (AI) in
      all types of adenoma (tubular: 1.77+/-0.35%, tubulovillous: 2.38+/-0.41%;
      villous: 3.3+/-0.39%) as well as loss of compartmentalization of proliferating
      and dying cells. In carcinomas a shift towards proliferation was evident, as
      shown by lower AIs than in adenomas (0.9+/-0.68% and 1.1+/-0.12% for moderately
      and poorly differentiated tumours), higher Ki67 indices (38.32+/-2.23% and 57+/
      3.89%, respectively) and higher mitosis (0.9+/-0.56% and 1.21+/-0.17%,
      respectively). However, apoptosis was observed in all tumours and is available as
      a target for therapeutic intervention. Expression of the apoptosis related
      proteins bcl-2 and bak also reflected loss of compartmentalization. While bcl-2
      did not show a consistent relationship to AI in tumour specimens, bak was
      positively correlated with apoptosis in 4 of 8 adenomas and 4 of 7 carcinomas,
      suggesting a role for this protein in the induction of apoptosis in a subset of
      tumours.

PMID- 9645441
TI  - CD57 (Leu-7) expression is helpful in diagnosis of the follicular variant of
      papillary thyroid carcinoma.
AB  - CD57 (HNK-1) is a oligosaccharide antigen that is expressed by cells of several
      lineages. It is present on multipotential neuroepithelial cells during
      embryogenesis, and tumours of epithelial, neuroectodermal and nerve sheath origin
      also express CD57. Its role in the diagnosis of thyroid tumours is controversial.
      We have studied CD57 expression by immunohistochemistry to determine its utility
      in the classification of thyroid follicular lesions. Study material included 114
      normal thyroid sections, 77 benign thyroid lesions (29 colloid nodules, 22
      follicular adenomas, 20 cases of Hashimoto's thyroiditis and 6 of Grave's
      disease) and 83 thyroid carcinomas, including 31 follicular variants of papillary
      carcinoma. We observed CD57 positivity in 95% of thyroid carcinomas, 27% of
      follicular adenomas and 10% of colloid nodules. It was not expressed in the
      normal thyroid. CD57 expression in thyroid carcinomas was significantly different
      from that in normal and benign thyroid lesions (P < 0.0001). The follicular
      variant of papillary thyroid carcinoma also showed significantly higher CD57
      expression than colloid nodules (P < 0.0009) or follicular adenomas (P < 0.0009).
      No significant difference was seen between colloid nodules and follicular
      adenomas. We conclude that CD57 immunohistochemistry is valuable in the
      classification of thyroid follicular lesions into benign and malignant groups and
      is also helpful in the diagnosis of the follicular variant of papillary thyroid
      carcinoma.

PMID- 9645442
TI  - Mammary foam cells. Characterization by immunohistochemistry and in situ
      hybridization.
AB  - Cells showing abundant, finely vacuolized cytoplasm (foam cells) are found
      frequently in most benign lesions of the breast and in certain malignant breast
      tumours. The origin of mammary foam cells (FCs) has not been clarified, and we
      therefore studied the morphological features of mammary FCs in a series of 50
      benign lesions. The FCs were subdivided, on the basis of their distribution into
      FCs lining the glandular lumina, intraluminal FCs, intraepithelial-pagetoid FCs,
      and stromal FCs. The lesions were tested with a panel of antibodies against
      macrophage (MAC 387, CD68) and epithelial (epithelial membrane antigen [EMA],
      gross cystic disease fluid protein 15 [GCDFP15] and cytokeratin) markers. The
      lesions were examined for the presence of PIP/GCDFP15-specific mRNA by an in situ
      hybridization technique. Three different types of FCs were identified. Type A FCs
      are epithelial cells (positivity with EMA and cytokeratin) and show apocrine
      differentiation (positivity with GCDFP15 antiserum and expression of PIP/GCDFP15
      mRNA). Type B FCs are of macrophage origin, as they are positive with the
      macrophage markers and lack cytokeratin and PIP/GCDFP15 mRNA. Finally, type C FCs
      show an intermediate profile between an epithelial cell and a macrophage: they
      are both CD68 and GCDFP15 positive and show a thin peripheral rim of positivity
      with anti-cytokeratin antibody. They lack PIP/GCDFP15 mRNA. Our results indicate
      the possibility of a spectrum of phenotypes in mammary FCs, from epithelial
      apocrine cells to macrophage-derived phagocytic cells.

PMID- 9645443
TI  - Bcl-2 protein and prognosis in patients with potentially curable non-small-cell
      lung cancer.
AB  - The bcl-2 proto-oncogene functions as a cell death suppressor, and its expression
      prolongs cell survival by blocking apoptosis. Data available on the clinical
      relevance of bcl-2 protein expression in patients with non-small-cell lung cancer
      (NSCLC) are controversial. We analysed the role of bcl-2 protein expression on 6
      year relapse-free survival in 229 patients with stage I-IIIa NSCLC (101 squamous
      cell carcinomas and 128 adenocarcinomas) subjected to surgery, with curative
      intent. Immunohistochemical analysis was performed on archival material by using
      a monoclonal antibody anti-bcl-2 (clone 124). Bcl-2 protein expression, which was
      detected in 22% of the cases, was significantly related to stage, histology and
      grading, and was an indicator of clinical outcome. The probability of relapse
      free survival at 6 years was longer for patients with bcl-2-positive tumours
      (74%) than for those with bcl-2-negative tumours (57%) (P=0.02). This finding was
      mainly evident for the subgroups of patients with stage IIIa tumours (P=0.05),
      squamous cell carcinoma (P=0.03) or moderately/poorly differentiated tumours
      (P=0.02). However, multivariate analysis by Weibull's regression model indicated
      that bcl-2 protein expression was not an independent prognostic risk factor in
      patients with curable NSCLC when the information provided by stage was available.

PMID- 9645444
TI  - Expression of bcl-2 oncoprotein in transitional cell carcinoma of the upper
      urinary tract.
AB  - We investigated the immunoreactivity for bcl-2 oncoprotein in 154 cases of
      transitional cell carcinoma of the upper urinary tract (TCC-UUT) and its relation
      with the immunoreactivity for p53 oncoprotein and proliferating cell nuclear
      antigen (PCNA) immunoreactivity. Immunohistochemically, bcl-2 oncoprotein was
      recognized as positive in 29.2% of the samples. The immunoreactivity for bcl-2
      oncoprotein was significantly (P < 0.05) correlated only with stage, though there
      was a borderline correlation (P = 0.050) with PCNA immunoreactivity. Furthermore,
      in invasive TCC the immunoreactivity for bcl-2 oncoprotein was associated with
      PCNA immunoreactivity (P < 0.041). The 5-year disease-free and overall survival
      rates were 55.7% and 71.5%, respectively. A univariate analysis of survival
      revealed that stage, grade, pattern of growth, immunoreactivity for p53
      oncoprotein, and PCNA immunoreactivity each had a significant effect on disease
      free and overall survival rates, whereas the immunoreactivity for bcl-2
      oncoprotein had no significant effect on either rate. In the final models of the
      multivariate analysis, stage was found to be the only prognostic factor for
      disease-free survival and for overall survival. Detection of immunoreactivity for
      bcl-2 oncoprotein appears to be of no real value in deciding the prognosis of TCC
      UUT.

PMID- 9645445
TI  - Ovarian-like stroma in an invasive mucinous cystadenocarcinoma of the pancreas
      positive for inhibin. A hint concerning its possible histogenesis.
AB  - A female patient with a mucinous cystadenocarcinoma originating from a mucinous
      cystadenoma of the pancreas is presented. The cystic tumour was diagnosed 3 years
      before and was treated with interventional external and internal surgical
      drainage before radical resection was accomplished by left hemipancreatectomy.
      Histology showed simultaneous occurrence of mildly dysplastic and invasive
      malignant epithelium. Immunohistology revealed inhibin-positive cells in the
      ovarianlike stroma of the tumour. The demonstration of ovarian-like stroma
      positive for inhibin suggests that this could be a hamartoma with dispersed sex
      cord stroma, which would explain the predominance of the female gender in
      mucinous cystic tumours of the pancreas.

PMID- 9645446
TI  - Bleomycin-induced pulmonary fibrosis in rat is associated with increased
      expression of collagen-binding heat shock protein (HSP) 47.
AB  - Increased accumulation of collagens in extracellular matrix (ECM) is mainly
      responsible for bleomycin-induced pulmonary fibrosis in rats. This study was
      designed to assess whether increased collagen accumulation in bleomycin-induced
      pulmonary fibrosis is associated with heat shock protein (HSP) 47, a molecular
      chaperone for collagen biosynthesis. We investigated the expression of type I and
      type III collagens and HSP47 in bleomycin-induced pulmonary fibrosis. Fifteen
      male Wistar rats were divided into two groups; group I: bleomycin-induced
      pulmonary fibrosis; group II: PBS-treated age-matched control rats. Pulmonary
      fibrosis was induced by injecting a single dose of bleomycin sulphate (5 U/kg
      body weight) intratracheally. Three bleomycin-treated rats and two age-matched
      control rats were sacrificed at the end of each of the 1st, 2nd and 4th weeks of
      the experiment. In bleomycin-treated rats, histological examination revealed
      pulmonary fibrosis, which increased with time. Increased type I and type III
      collagen desposition was observed in the lungs of all the bleomycin-treated rats.
      Weak immunostaining of HSP47 was noted in the control lungs. In contrast, strong
      immunostaining for HSP47 was seen in all the bleomycin-treated fibrotic lungs. In
      addition, increased numbers of phenotypically altered myofibroblasts (alpha
      smooth muscle actin immunopositive) and fibroblast (vimentin immunopositive) were
      seen in bleomycin-treated lungs and found to express HSP47. Parallel increase of
      collagens and their molecular chaperone HSP47 expression was found in the
      bleomycin-treated lungs, and their co-localization could be detected by double
      immunostaining. Overexpression of HSP47 may play a significant part in the
      excessive assembly of collagens and could contribute in this way to the fibrosis
      found in bleomycin-treated rat lungs.

PMID- 9645447
TI  - Spontaneous myocarditis in DBA/2 mice. Light microscopic study with transmission
      and X-ray analytical electron microscopic studies.
AB  - DBA/2 inbred mice spontaneously develop myocarditis and a unique form of
      subepicardial inflammation of the right ventricle characterized by a prominent
      eosinophilic infiltrate with calcinosis. We studied this myocarditis using light
      microscopy and both transmission and analytical X-ray electron microscopy, paying
      particular attention to eosinophil-associated cardiocyte injury. At 5 weeks of
      age, many eosinophils and mononuclear cells (MNCs) were seen in the subepicardium
      of the right ventricle. Electron microscopy showed that cardiocytes underwent
      degenerative changes, including myofibrillar lysis, accumulation of Z-band
      material and mitochondrial inclusions, and rupture of plasma membranes. The
      infiltrating eosinophils appeared to be activated, and cells with cytoplasmic
      vacuoles, suggestive of degranulation, were noted. The myocardial injury was most
      severe in the 7th week and healed with myocardial fibrosis and calcinosis by the
      8th week. Analytical X-ray electron microscopy showed that the calcinosis was
      initiated in mitochondrial inclusions of injured cardiocytes. The peripheral
      eosinophil count did not increase during the course of the disease, but there was
      a positive correlation between the ratio of eosinophils to infiltrated white
      blood cells (Eo/WBCs) in the right ventricle and the severity of myocardial
      damage. Eosinophils may play a significant part in subepicardial cardiocyte
      injury seen in DBA/2 mice.

PMID- 9645448
TI  - Pancreatic leiomyosarcoma. Case report with immunohistochemical and flow
      cytometric studies.
AB  - A leiomyosarcoma originating from the pancreas of a 57-year-old man is presented.
      A 6x5x4 cm tumour was located in the head region, and the patient underwent
      surgical palliation. Immunohistochemical studies excluded an epithelial origin; a
      myogenic origin was suggested by strong vimentin and smooth muscle actin
      positivity. Flow cytometric analysis revealed an aneuploid pattern (DNA index:
      1,561). The patient died with widespread metastases 7 month after the operation.

PMID- 9645449
TI  - Coexisting primary early gastric plasmacytoma and sarcoidosis with
      hypercalcaemia.
AB  - We report on a 61-year-old woman with coexisting early stage primary gastric
      plasmacytoma and sarcoidosis with hypercalcaemia. Laboratory data on admission
      showed hypercalcaemia, with 12.8 mg/dl, parathyroid hormone-related peptide
      (PTHrP) 1.2 pmol/l, C-PTHrP 69.5 pmol/l, and 1,25-dihydroxyvitamin D3 46.7 pg/ml.
      Neoplastic plasma cells proliferated in the propria mucosa of the stomach, showed
      a monoclonal immunoglobulin of cytoplasmic IgA (lambda light chain) and were
      positive for leucocyte common antigen and epithelial membrane antigen on paraffin
      section prepared from a stomach biopsy specimen. Russel bodies were present, as
      were crystals. Abundant sarcoid granulomas were observed in many of the regional
      lymph nodes around the stomach and in the dermis of a skin nodule. The patient
      underwent subtotal gastrectomy with administration of antimyeloma chemotherapy.
      We suggest that the hypercalcaemia in this patient was due to PTHrP production by
      neoplastic plasma cells.

PMID- 9645450
TI  - Primary manifestation of Hodgkin's disease in the central nervous system.
AB  - A 62-year-old woman presented with loss of memory and a mild hemiparesis.
      Neuroradiology demonstrated a left frontoparietal tumour. Biopsy specimens of
      this lesion revealed intracerebral Hodgkin's lymphoma, a diagnosis supported by
      immunohistochemical reactions of the tumour cells for the CD30 antigen.
      Additional cell cycle studies revealed a high proliferative activity of the
      tumour cells in association with absence of apoptosis. There was no evidence that
      overexpression of bcl-2 or Epstein-Barr virus infection was involved in the
      pathogenesis of this neoplasm. Lymphomas in the lung were detected 3 months
      later. Following neurosurgical excision, radiotherapy, and chemotherapy, the
      patient had no evidence of Hodgkin's disease after 13 months of follow-up.

PMID- 9645451
TI  - Expression of Lewis antigens in papillary carcinoma of the thyroid gland.

PMID- 9645452
TI  - Microsatellite instability is rare in the clinical course of myelodysplastic
      syndrome studied with DNA from fresh and paraffin-embedded tissues.
AB  - Microsatellite instability (MSI) has been reported to occur in various types of
      malignant neoplasms. We performed a polymerase-chain-reaction-based assay for MSI
      between the initial and the most recently available ("latest") samples from 23
      patients with myelodysplastic syndrome (MDS). Of these patients, 15 were
      informative at more than three microsatellite loci. Seven patients showed an
      increase in leukemic cells while 8 patients did not during the interval between
      the two analyses. Only 1 of the patients, who had refractory anemia with excess
      blasts, which changed to acute myelogenous leukemia, showed microsatellite
      alteration at the analysis times. Among all 23 patients, two alterations were
      detected in the 42 informative paired samples that showed an increase in leukemic
      cells (4.8%), while none was detected in the 59 paired samples without such an
      increase. In total, therefore only two alterations were detected among 101
      informative paired samples (2%). This indicates that MSI is rare in the clinical
      course of MDS irrespective of disease status, and is consequently not a critical
      genetic event for disease progression in most MDS patients.

PMID- 9645453
TI  - Greater antitumor efficacy of paclitaxel administered before epirubicin in a
      mouse mammary carcinoma.
AB  - Combined treatment with paclitaxel and anthracyclines is increasingly being
      tested in clinical practice. Epirubicin is in general administered before
      paclitaxel. We have investigated, using a murine mammary adenocarcinoma, whether
      the efficacy and toxicity of this combination is influenced by treatment
      sequence, different time intervals and dose intensity. The tumor was transplanted
      into the right hind foot of C3D2F1 female mice. Paclitaxel was administered i.p.
      in doses ranging from 15 mg/kg to 75 mg/kg and epirubicin (i.p. or i.v.) in doses
      from 9 mg/kg to 30 mg/kg. The hepatic and peritoneal toxicity observed with
      epirubicin administration increased in combined treatments (stronger with i.p.
      than i.v. epirubicin administrations) and was dose-dependent. When paclitaxel and
      epirubicin were administered simultaneously or paclitaxel was given 24 h before
      epirubicin, the same tumor growth delays were obtained in all groups. A smaller
      effect was observed when paclitaxel was administered 24 h after epirubicin.
      Increasing the epirubicin or paclitaxel dose led to higher tumor growth delays
      but also an increased toxicity. In conclusion, in this experimental model, the
      administration of 45 mg/kg paclitaxel before 15 mg/kg epirubicin was very
      effective and the increased toxicity can be limited by introducing an interval of
      24 h between drug administrations. These results should be considered when
      designing clinical trials.

PMID- 9645454
TI  - Expression of the active form of MMP-2 on the surface of leukemic cells accounts
      for their in vitro invasion.
AB  - The enhanced expression of matrix metalloproteinases (MMP), especially
      gelatinases MMP-2 and MMP-9, has been associated with the invasive behavior of
      tumor cells. Previously we reported that primary acute myelogenous leukemia
      blasts and human leukemic cultured KG-1 cells but not HEL cells penetrate a
      reconstituted basement membrane (Matrigel) in an invasion assay. In this study,
      we investigated the role of MMP-2 and MMP-9 in in vitro invasion by leukemic
      cells. We found that both recombinant human tissue inhibitor of metalloproteinase
      2 (rhTIMP-2) and anti-MMP-2 antibody inhibit the invasiveness of KG-1 cells in
      the Matrigel assay (by 76% and 51% respectively), while anti-MMP-9 antibody does
      not, indicating that MMP-2 but not MMP-9 in involved in the invasive process. KG
      1 cells were found to secrete constitutively the latent (but not the activated)
      forms of both MMP-2 and MMP-9 and, after stimulation with the phorbol ester 12-O
      tetradecanoylphorbol 13-acetate (TPA), higher levels of these pro-MMP. TPA
      stimulation, however, did not increase the in vitro invasiveness of these cells.
      Analysis by Western blot and flow cytometry revealed the presence of the
      activated form of MMP-2 (64 kDa) on the surface of KG-1 cells and primary AML
      blasts, as well as MT-MMP in the homogenates of these cells. This active form of
      MMP-2 was not detected on the surface of HEL cells, which were non-invasive in
      vitro, although these cells secreted pro-MMP-2. In conclusion, leukemic KG-1 and
      primary acute myelogenous leukemia cells, which secrete pro-MMP-2 and pro-MMP-9,
      were also shown to express the activated form of MMP-2 on their cell surface. We
      suggest that this active form is essential to the in vitro invasion of leukemic
      cells.

PMID- 9645455
TI  - The expression of the mdm2 gene may be related to the aberration of the p53 gene
      in human hepatocellular carcinoma.
AB  - The relationship between mdm2 gene expression and p53 gene mutation in
      hepatocellular carcinoma (HCC) and their correlation with the invasiveness of the
      disease were investigated in this study. Either the expression level of the mdm2
      gene or the mutation rate of the p53 gene was higher in HCC than in paratumor
      liver tissues. Studies on the relationship between mdm2 and p53 revealed that
      mdm2 gene expression in HCC without p53 mutation was higher than when there was
      p53 mutation, while the p53 mutation rate in HCC with mdm2 overexpression was
      significantly lower than in HCC without mdm2 overexpression. Among 23 HCC with
      invasion, mdm2 gene overexpression was found in 6 patients while p53 mutation was
      found in the other 11 patients, and only 1 patient was found to have both mdm2
      overexpression and p53 mutation. These results indicated that either mdm2
      overexpression or p53 mutation may be related to the invasiveness of HCC.
      Considering that an autoregulatory feedback loop between the mdm2 and p53 genes
      may exist, wild-type P53 can induce the expression of mdm2 via a p53-binding site
      in the mdm2 gene, while MDM2 protein functions as a negative regulator of P53
      protein. These results also suggest that mdm2 may be related to the high
      invasiveness of HCC through inactivating the tumor-suppressor function of the p53
      gene.

PMID- 9645456
TI  - Evaluation of the tumorigenic and angiogenic potential of human fibroblast growth
      factor FGF3 in nude mice.
AB  - Recently, the expression of fibroblast growth factor 3 (FGF3) was found in 55% of
      human Kaposi's sarcoma (KS) tumor tissues examined, while almost no expression of
      FGF3 was found in normal skin. To further these studies, human FGF3 cDNA were
      constructed by the overlap-extension method. The proteins translated from two
      FGF3 cDNA, which differ only in the sequences preceding the AUG presumed to be
      the initiation codon, were shown to have the same molecular mass. This result
      suggests that translation of human FGF3, which is different from mouse FGF3,
      begins only at the AUG site. The human FGF cDNA was transfected into NIH3T3
      cells. The NIH 3T3 cells transformed by FGF3 were then injected subcutaneously
      into athymic nude mice. Nodular lesions developed at the injection sites in all
      seven mice injected with the F3-1 cell clone, which showed high expression of
      FGF3, and in two out of six mice injected with the F3-2 cell clone, which
      expressed a low level of FGF3. Histopathological features of these tumors
      contained fascicles of spindle-shaped cells surrounding irregular endothelial
      lined vascular clefts, similar to those observed in human KS lesions.
      Immunohistochemical staining for factor V111 antigen revealed reactivity in
      multiple areas, especially in abundant vascular structures of the tumor sections
      examined. The expression of FGF3 together with the FGF receptors FGFR1, FGFR2,
      and FGFR3, was detected in the mouse tumors by Northern blot analysis. Our
      results indicate that tumors induced by FGF3-transformed NIH3T3 cells show some
      similarities to human KS tumors. In conclusion, our results demonstrate the
      potential tumorigenic and angiogenic role of human FGF3.

PMID- 9645457
TI  - Continuous-infusion granisetron compared to ondansetron for the prevention of
      nausea and vomiting after high-dose chemotherapy.
AB  - PURPOSE: The serotonin receptor antagonists effectively prevent emesis with
      little toxicity when employed with standard doses of emetogenic chemotherapy. The
      optimal approach to the prevention of the emesis associated with the high doses
      of chemotherapy used for autologous stem cell transplantation is not known. A
      randomized controlled trial was designed to assess the relative efficacy and
      toxicity of granisetron compared to ondansetron in the setting of autologous stem
      cell transplantation. METHODS: A group of 48 patients with breast cancer were
      randomized in a double-blind fashion to receive either (1) granisetron as a 0.5
      mg i.v. bolus 30 min. before chemotherapy followed by a continuous infusion of
      0.04 mg/h (1 mg/day) for 7 days or (2) ondansetron as an 8-mg i.v. bolus 30 min
      before chemotherapy followed by a continuous infusion of 1 mg/h (24 mg/day) for 7
      days. All patients also received 10 mg dexamethasone/day i.v. for 7 days.
      Chemotherapy consisted of 1500 mg cyclophosphamide per m2/day, 125 mg thiotepa m(
      2) day(-1), and 200 mg carboplatin per m2/day all as a continuous infusion for 4
      consecutive days. The two study arms were then compared for the incidence and
      severity of nausea, incidence of emesis, number of salvage anti-emetics required,
      cost, and toxicity. RESULTS: A total of 46 patients were evaluable. The treatment
      arms were well-balanced for known risk factors for chemotherapy-induced nausea
      and vomiting. Compliance with self-reporting of nausea and vomiting was poor but
      indicated no difference between the two treatment arms. The average number of
      anti-emetics required was 15.8 in both treatment arms and the average time to the
      first dose of a salvage anti-emetic was 2.8 days in the granisetron arm and 2.9
      days in the ondansetron arm. The incidence of headache was 36 % in the
      granisetron arm and 39 % in the ondansetron arm. None of these differences was
      statistically significant. The use of granisetron resulted in a cost saving of
      6.5 %. CONCLUSION: There was no significant difference between granisetron and
      ondansetron in either efficacy or toxicity. At our institution, the use of
      granisetron resulted in a moderate cost saving.

PMID- 9645458
TI  - The operative management of a malignant proximal humerus tumor represented by
      secondary Paget's osteosarcoma.
AB  - PURPOSE: Malignant tumors at the proximal humerus are an operative challenge.
      Radical removal is a principal of tumor surgery but as much functionality as
      possible should be retained. These conditions often conflict so a compromise has
      to be reached. This paper proposes a solution to this dilemma, introducing an
      operative approach, with a new modular prosthesis, to a secondary Paget's
      osteosarcoma in the proximal humerus. METHODS AND RESULTS: A recently developed
      humerus modular prosthesis is described, which has been implanted into a patient
      with Paget's osteosarcoma. In these, mostly elderly, patients, successful
      operative therapy should combine radical removal with early mobilization. Paget's
      osteosarcoma is a recognized complication of the disease, and its prognosis is
      poor. In our patient, the implanted humerus prosthesis allowed a limb-saving
      procedure to be combined with radical removal of the tumor and postoperative
      early mobilization. A 3-month follow-up yielded good results with no recurrence
      of the disease and the patient had satisfactory movement. She was able to resume
      normal daily life shortly after the operation. CONCLUSION: Implantation of a
      modular prosthesis of the humerus may allow radical removal of a malignant tumor
      in that area while achieving early motion. In the literature, amputation is often
      advocated, as radical treatment with chemotherapy is not a successful option in
      this elderly patient group. We think the alternative use of a modular prosthesis
      of the humerus is possible in selected cases. We have encountered no other case
      in the literature where a limb-saving procedure attempts to preserve as much
      functionality as possible in Paget's osteosarcoma.

PMID- 9645459
TI  - Improved long-term survival for unresectable hepatocellular carcinoma (HCC) with
      a combination of surgery and intrahepatic arterial infusion of 131I-anti-HCC mAb.
      Phase I/II clinical trials.
AB  - Resectional therapy has been accepted as the only curative therapy for
      hepatocellular carcinoma (HCC). Unfortunately, it is estimated that only 10% of
      HCC are resectable at the time of diagnosis. Cytoreduction and sequential
      resection offer a new hope for patients with unresectable HCC. Radioimmunotherapy
      (RIT) is an attractive approach for cytoreduction. We have previously shown that
      intrahepatic arterial 131I-labelled anti-HCC monoclonal antibody (131I-Hepama-1
      mAb) could be used safely in combination with hepatic artery ligation for
      treatment of unresectable HCC, and encouraging results have been achieved. In
      this paper, the long-term survival and the prognostic factors in HCC patients
      treated with radioimmunotherapy will be analysed. Sixty-five patients with
      surgically verified unresectable HCC were treated with hepatic artery ligation
      plus hepatic artery cannulation and infusion from 1990 to 1992. Thirty-two
      patients were enrolled in a phase I-II clinical trial with infusion of 131I
      radiolabelled anti-HCC monoclonal antibody (Hepama-1 mAb) via the hepatic artery
      (the RIT group). Another 33 patients formed the group treated with intrahepatic
      arterial chemotherapy (the non-RIT group). T cell subsets were measured in 24
      patients and human anti-(murine Ig) antibody (HAMA) were monitored in the RIT
      group. The 5-year survival rate was significantly higher in the RIT group than in
      the chemotherapy group, being 28.1% compared to 9.1% (P < 0.05); this was mainly
      a result of better cytoreduction and a higher sequential resection rate (53.1%
      compared to 9.1%). Significant prognostic factors in the RIT group included
      tumour capsule status and the number of tumour nodules. HAMA incidence and CD4+ T
      lymphocytes influenced short-term, but not long-term survival. It is suggested
      that intrahepatic-arterial RIT, using 131I-Hepama-1 mAb, combined with hepatic
      artery ligation might be an effective approach to improve long-term survival in
      some patients with unresectable HCC, which may successfully be made resectable by
      intra-arterial infusion of 131I-Hepama-1 mAb.

PMID- 9645460
TI  - Methodological problems of grading tumour regression: responders compared to non
      responders.

PMID- 9645461
TI  - Gene therapy: application to disease. The Seventh International Symposium of the
      Hiroshima Cancer Seminar, November 1997, Hiroshima, Japan.

PMID- 9645462
TI  - Pharmacoeconomic evaluation of high-dose chemotherapy and peripheral blood stem
      cell support in high-risk or poor-prognosis malignancies.
AB  - Discussion of the total costs and cost-effectiveness ratios of patients receiving
      high-dose chemotherapy (HDC) and peripheral blood stem cell support (PBSCS) is
      controversial. In Germany, no reliable data are available, whereas in other
      countries this issue has been extensively studied. We performed a
      pharmacoeconomic evaluation on all patients (n = 37) treated with HDC and PBSCS
      at our institution between July 1994 and June 1997. Patients suffered from high
      risk or poor-prognosis breast cancer (n = 24), Hodgkin's disease (n = 3), high
      grade non-Hodgkin's lymphoma (n = 4), multiple myeloma (n = 2), small-cell
      cervical cancer (n = 1), malignant hystiocytosis (n = 1) and testicular cancer (n
      = 2). For pharmacoeconomic evaluation, the period from initiation of induction
      chemotherapy (IC) until reconstitution after the last course of HDC and PBSCS was
      considered. A total of 18 patients received IC/HDC/PBSCS for locally advanced or
      systemic disease, and 19 patients received adjuvant or consolidation
      IC/HDC/PBSCS. Treatment protocols were heterogeneous. Patients were treated with
      two to five courses (median two) respectively of IC and sequential mono-HDC (n =
      26), tandem-HDC (n = 10) or triple-HDC (n = 1). All patients received
      granulocyte/macrophage-colony-stimulating factor (G-CSF) for stem cell
      mobilisation and for amelioration of neutropenia after HDC. The relative costs
      (based on supplier prices) for the total amount of drugs prescribed during the in
      patient period was 29.8% for G-CSF, 35.8% for blood products 18.5% for
      chemotherapy, 2.4% for antiemetics, 5.9% for antimicrobial drugs and 7.6% for
      other drugs. Contrary to expectations, antimicrobial drugs had only a minor
      pharmacoeconomic impact during IC/HDC/PBSCS in patients with high-risk or poor
      prognosis malignancies, indicating that prolonged septic complications were
      uncommon in our institution. We conclude that pharmacoeconomic evaluations in IC/
      HDC/PBSCS might be integrated into the effort to ensure quality control and
      monitoring.

PMID- 9645463
TI  - Perpetually mobile footprints of ancient infections in human genome.
AB  - Up to 1% of the human genome is represented by human endogenous retroviruses
      (HERVs) and their fragments that are likely footprints of ancient primate germ
      cell infections by retroviruses that occurred 10-60 million years ago. HERV
      solitary long terminal repeats (LTRs) can be often met in close vicinity to
      functional genes. The LTRs comprise a set of regulatory sequences like promoters,
      enhancers, hormone responsive elements and polyadenylation signals that might
      come out as new regulatory signals to resident genes and thus change their
      regulation in evolution. Moreover, the LTRs have a potential for chromatin
      remodeling that can also modulate gene expression. This review describes the
      integration specificity and distribution of the HERVs and LTRs in the human
      genome and discusses possible functional consequences of their integration in the
      vicinity of genes.

PMID- 9645464
TI  - A novel system of peptidergic regulation.
AB  - Systematic analysis of structure and biological activity of peptide components of
      tissue extracts and biological fluids allows us to formulate a novel concept of a
      peptidergic regulatory system, complementary to the conventional regulatory
      systems (i.e. nervous, endocrine and paracrine systems). According to that
      concept, the proteolytic degradation of tissue proteins carried out by a specific
      and regulated system of tissue-specific enzymes and protein substrates gives rise
      to a large group of peptides, which we define as tissue-specific peptide pool. As
      a result, functional proteins provide their proteolytically derived fragments for
      maintaining tissue homeostasis.

PMID- 9645465
TI  - Effects of the amyloid protein precursor of Alzheimer's disease and other ligands
      of the LDL receptor-related protein on neurite outgrowth from sympathetic neurons
      in culture.
AB  - The amyloid protein precursor (APP) of Alzheimer's disease can stimulate neurite
      outgrowth in vitro. The receptor responsible for this effect has not been
      identified. Kunitz protease inhibitor (KPI)-containing forms of APP bind to the
      low-density lipoprotein receptor-related protein (LRP). As LRP may regulate
      neurite outgrowth, we examined whether the effects of APP are mediated by LRP.
      Inhibitors of LRP decreased neurite outgrowth from chick sympathetic neurons.
      Most LRP ligands (alpha2-macroglobulin, lactoferrin, and lipoprotein lipase)
      stimulated outgrowth. However, in soluble form, the KPI-containing APP751 was a
      weak inhibitor of outgrowth. In substrate-bound form, both APP751 and APP695
      (which does not bind to LRP) stimulated outgrowth. Thus the effect of substrate
      bound APP on neurite outgrowth is not mediated by LRP.

PMID- 9645466
TI  - Quantitative analysis of a cysteine351glycine mutation in the G protein Gi1alpha:
      effect on alpha2A-adrenoceptor-Gi1alpha fusion protein activation.
AB  - Fusion proteins were constructed between the porcine alpha2A-adrenoceptor and
      either wild-type (Cys351) or a pertussis toxin-resistant (Gly351) form of the G
      protein Gi1alpha. Addition of adrenaline to membranes expressing the fusion
      proteins resulted in concentration-dependent stimulation of their high affinity
      GTPase activity. The alpha2A-adrenoceptor-wild type Gi1alpha fusion protein
      produced substantially higher maximal stimulation of GTPase activity in response
      to adrenaline than that containing Gly351 Gi1alpha. Treatment of the fusion
      proteins as agonist-regulated enzymes allowed measurement of Vmax and turnover
      number for adrenaline-stimulation of the GTPase activity of each fusion
      construct. The turnover number of the alpha2A-adrenoceptor-Cys351 Gly Gi1alpha
      fusion protein was only 44'S, of that for the alpha2A-adrenoceptor-wild type
      Gi1alpha fusion protein. These data provide the first direct quantitative
      evaluation of the effects of a mutation of a G protein on the capacity of an
      agonist-occupied receptor to activate the mutant.

PMID- 9645467
TI  - Staurosporine-sensitive protein phosphorylation is required for postreplication
      DNA repair in human cells.
AB  - DNA repair is an important factor of stability of pro- and eukaryotic genomes
      which plays a central role in mutagenesis and carcinogenesis. Genetic control of
      nucleotide excision repair (NER) in mammalian cells is well studied, but little
      is known about molecular mechanisms of postreplication repair (PRR) which allows
      bypass of base lesions in template strands after DNA replication. In
      Saccharomyces cerevisiae PRR is controlled by the RAD61RAD18 pathway which
      involves POL30 gene encoding proliferating cell nuclear antigen (PCNA), and in
      human cells PCNA is known to be closely associated with the newly replicated
      chromatin where PRR probably takes place. In UV-irradiated human cells distinct
      PCNA foci may be detected in some cells which accumulate phosphorylated breast
      cancer susceptibility protein BRCA1 and another protein BARD1. Human PCNA is also
      known to be phosphorylated after UV-irradiation. In this study we found that the
      known inhibitor of protein kinases staurosporine supresses PRR in NER-deficient
      cells which is consistent with the view that BRCA1 and PCNA are required for PRR.
      We also have shown that the distinct PCNA foci in UV-irradiated NER-deficient
      cells are actually associated with the newly replicated chromatin. Since RAD18
      protein is not essential for normal DNA replication and directly controls PRR in
      yeast, we analysed whether this protein as well as its human homologs (HR18A and
      HR18B) have common domains with BRCA1 and BARD1. It is found that HR18A has a
      subregion of homology to BARD1 and HR18A-to BRCA1. Taken together the results
      indicate that BRCA1 and BARD1 may be involved in PRR in human cells.

PMID- 9645468
TI  - The murine gap junction gene connexin36 is highly expressed in mouse retina and
      regulated during brain development.
AB  - A new gap junction gene isolated from rat brain cDNA, mouse retina cDNA and mouse
      genomic DNA is called connexin36, since it codes for a connexin protein of 321
      amino acids corresponding to the theoretical molecular mass of 36045 kDa (rat)
      and 36084 kDa (mouse). Only one amino acid residue differs between rat and mouse
      connexin36. In the single murine connexin36 gene, an 1.14-kb intron interrupts
      the coding region, similar as in the homologous skate connexin35 gene. Because of
      this unique feature, mouse connexin36 differs from the other 13 murine connexin
      genes and is suggested to form a new delta subclass of connexins. Connexin36 mRNA
      (2.9 kb) is highly expressed in adult retina and less abundant in brain where it
      gradually increased during fetal development until day 7 post partum, and
      decreased thereafter.

PMID- 9645469
TI  - Metabolism of 8-iso-prostaglandin F2alpha.
AB  - Tritium labelled (x=1.1 MBq/17.7 microg/kg) and unlabelled 8-iso-PGF2alpha (43
      microg/kg) were administered intravenously to female rabbits and frequent blood
      and continuous urinary samples were collected up to 4 h. The total radioactivity
      was lost rapidly from the circulation. About 80% of the total radioactivity was
      found in urine within 4 h. The plasma half-life of 8-iso-PGF2alpha is found to be
      1 min at the distribution phase. The terminal elimination phase half-life was
      about 4 min. At 1.5 min after administration 64%, 19% and 13% of the plasma
      radioactivity represented 8-iso-PGF2alpha, 15-keto-8-iso-PGF2alpha and beta
      oxidised products, respectively. The values for 20-min plasma were 5%, 2%, and
      88%. The radiochromatograms from 10 min-4 h urinary samples were dominated by
      more polar beta-oxidised products. Alpha-Tetranor-15-keto-13,14-dihydro-8-iso
      PGF2alpha was identified as a major urinary metabolite.Thus, 8-iso-PGF2alpha
      metabolises in the rabbit mainly to several degraded polar metabolites through
      dehydrogenation at C-15, reduction of delta13-double bond and beta-oxidation, and
      excretes efficiently into the urine.

PMID- 9645470
TI  - Residues unique to the pro-hormone convertase PC2 modulate its autoactivation,
      binding to 7B2 and enzymatic activity.
AB  - The prohormone convertase PC2 is one of the major subtilisin/kexin-like enzymes
      responsible for the formation of small bioactive peptides in neural and endocrine
      cells. This convertase is unique among the members of the subtilisin/kexin-like
      mammalian serine proteinase family in that it undergoes zymogen processing of its
      inactive precursor proPC2 late along the secretory pathway and requires the help
      of a PC2-specific binding protein known as 7B2. We hypothesized that some of
      these unique properties of PC2 are dictated by the presence of PC2-specific amino
      acids, which in the six other known mammalian convertases are otherwise conserved
      but distinct. Accordingly, six sites were identified within the catalytic segment
      of PC2. Herein we report on the site-directed mutagenesis of Tyr194 and of the
      oxyanion hole Asp309 and the consequences of such mutations on the cellular
      expression and enzyme activity of PC2. The data show that the Y194D mutation
      markedly increases the ex vivo ability of PC2 to process proopiomelanocortin
      (POMC) into beta-endorphin in cells devoid of 7B2, e.g. BSC40 cells. In these
      cells, expression of native PC2 does not result in the secretion of measurable in
      vitro activity against a pentapeptide fluorogenic substrate. In contrast,
      secreted Y194D-PC2 exhibited significant enzymatic activity, even in the absence
      of 7B2. Based on co-immunoprecipitations and Western blots, binding assays
      indicate that Tyr194 participates in the interaction of PC2 with 7B2, and that
      the oxyanion hole Asp309 is critical for the binding of proPC2 with pro7B2.

PMID- 9645471
TI  - Plasma membrane NADH-coenzyme Q0 reductase generates semiquinone radicals and
      recycles vitamin E homologue in a superoxide-dependent reaction.
AB  - We investigated the ability of plasma membrane CoQ reductase (PMQR) purified from
      pig liver to reduce phenoxyl radicals of a vitamin E homologue, Trolox. We report
      that NADH-driven one-electron reduction of CoQ0 catalyzed by PMQR produced CoQ0
      semiquinone radical and CoQoH2. These in turn, recycle vitamin E homologue,
      Trolox, via reducing its phenoxyl radical. A significant part of NADH/PMQR
      catalyzed reduction of CoQ0 (and Trolox recycling) was superoxide-dependent.
      Overall, our results demonstrate that PMQR in the model system used can act as an
      antioxidant enzyme that recycles water-soluble homologues of coenzyme Q and
      vitamin E.

PMID- 9645472
TI  - Inhibition of ascorbate peroxidase under oxidative stress in tobacco having
      bacterial catalase in chloroplasts.
AB  - To analyze the potential of the active oxygen-scavenging system of chloroplasts,
      we introduced Escherichia coli catalase into tobacco chloroplasts. Photosynthesis
      of transgenic plants was tolerant to high irradiance under drought conditions,
      while the wild plants suffered severe damage in photosynthesis under the same
      conditions. Irrespective of responses to the stress, ascorbate peroxidase was
      completely inactivated both in the transgenic and wild-type plants. These
      findings are contrary to the established idea that the ascorbate peroxidase
      mediated antioxidative system protects chloroplasts from oxidative stress.

PMID- 9645473
TI  - The role of keratin filaments during nuclear envelope reassembly in Xenopus egg
      extracts.
AB  - We report here a new structure, named 'strings-of-pearls', which are seen to form
      in Xenopus egg extracts after incubation, as 200 nm membrane vesicles attach to
      10 nm filaments. These membrane vesicles fuse together along the filaments to
      form annulate lamellae (AL) or attach to demembranated sperm chromatin to
      initiate assembly of a nuclear envelope. Immunoassay with anti-keratin antibodies
      AE3 showed that the filaments were mainly composed of a 56 kDa keratin-like
      protein. Addition of AE3 to the extracts resulted in inhibition of AL formation
      and defective assembly of NE. These results suggest a function of keratins in the
      assembly of nuclear envelopes during Xenopus development.

PMID- 9645474
TI  - Contribution of arginine-82 and arginine-86 to catalysis of RNases from Bacillus
      intermedius (binase).
AB  - To elucidate the functional role of Arg82 and Arg86 in the enzyme activity of
      binase, the extracellular ribonuclease of Bacillus intermedius, we used site
      directed mutagenesis. On cleavage of various substrates the catalytic activity of
      binase mutant Arg86 Ala is 2.7 x 10(3) - 7.7 x 10(3) times less than that of the
      native enzyme. The decrease in activity is determined preferentially by the
      decrease in the molecular rate constant kcat with a relatively small change of
      enzyme-substrate affinity, characterized by Km. This is the expected result if
      Arg86 acts to lower the energy of a transition state of the reaction. The
      replacement of Arg82 by Ala causes a 5-19-fold activity decrease, depending on
      the substrate. We propose that this residue does not have a direct catalytic
      function in the molecular mechanism of the binase action and that the activity
      decrease of binase on the replacement of Arg82 by alanine is mediated by the
      effect of Arg82 on the pK of catalytic residues.

PMID- 9645475
TI  - A synthetic human Agouti-related protein-(83-132)-NH2 fragment is a potent
      inhibitor of melanocortin receptor function.
AB  - Chemical synthesis of Agouti proteins - Agouti and Agouti-related proteins - is
      complicated by their large size and by multiple cysteine residues located in the
      carboxyl terminal regions. Three human Agouti-related protein (AGRP) fragments,
      two of which correspond to a proposed endoprotease cleavage site between amino
      acids 82 and 83, were synthesized and tested for anti-melanotropic activity using
      Xenopus laevis dermal melanophores. Amino-terminal fragments AGRP(25-51) and (54
      82) were devoid of significant antagonist activity, whereas the amidated carboxyl
      terminal AGRP fragment (83-132)-NH2 was potently active with an inhibitory
      equilibrium dissociation constant (Ki) of 0.7 nM. The ability to synthesize
      functionally active AGRP should help unravel its role in the central nervous
      system and its unusual properties with respect to interaction with the
      melanocortin family of G-protein coupled receptors.

PMID- 9645476
TI  - Human natural resistance-associated macrophage protein is a new type of
      microtubule-associated protein.
AB  - Natural resistance-associated macrophage protein 1 (NRAMP1) is a putative
      membrane protein that dominates natural resistance to infection. An NRAMP1
      glutathione S-transferase fusion protein was used to test the ability of the
      NRAMP1 NH2-terminal domain to bind to taxol-stabilized microtubules. Co
      sedimentation analysis showed that the fusion protein binds to microtubules.
      Although the NH2-terminal domain of the NRAMP1 molecule has structural homology
      with the Pro-rich region of microtubule-associated protein 4 (MAP4), the presence
      of the MAP4 microtubule-binding domain fragment had little effect on the binding
      of the fusion protein to microtubules.

PMID- 9645477
TI  - Efficient introduction of alkene functionality into proteins in vivo.
AB  - The methionine analogue 2-amino-5-hexenoic acid (homoallylglycine, Hag) can be
      utilized by Escherichia coli in the initiation and elongation steps of protein
      biosynthesis. Use of an E. coli methionine auxotroph and Hag-supplemented medium
      resulted in replacement of ca. 85% of the methionine residues in mouse
      dihydrofolate reductase expressed under control of a bacteriophage T5 promoter. N
      terminal sequencing indicated 92+/-5% occupancy of the initiator site by Hag. The
      vinyl function of Hag remains intact in the purified protein and suggests new
      chemistries for modification of natural and artificial proteins prepared in
      bacterial hosts.

PMID- 9645478
TI  - Mutational analysis of Caenorhabditis elegans CED-4.
AB  - Much of our knowledge concerning the genetics that regulate cell death has come
      from the studies of cell death during the development of the nematode
      Caenorhabditis elegans. Of the 14 genes identified as components of nematode cell
      death pathways, two genes, ced-3 and ced-4, are required to promote cell death
      and a third, ced-9, blocks cell death. Recent studies show CED-4 to be an
      activator of CED-3 and CED-9 to be an inhibitor of CED-4. Two published sequence
      alignments suggest that CED-4 contains a death effector domain (DED), a protein
      sequence motif present in other death signaling proteins like Fadd and Flice; one
      study suggests a DED sequence similarity near the N-terminus while the other
      found sequence similarity near the C-terminus of CED-4. Using mutational analysis
      we have tested the functional significance of the conserved residues found within
      the putative DEDs of CED-4. Mutations in two conserved residues within the
      putative N-terminal DED of CED-4 affected its function, while mutations in the
      conserved residues within the putative C-terminal DED had no effect on CED-4
      function. Our results do not support the presence of a DED in the C-terminus of
      CED-4 and suggest a potential role for the N-terminus in CED-4 function, possibly
      as a DED or as a CARD (caspase recruitment domain). We also found that CED-9
      associated with all the CED-4 mutants and inhibited the activity of all the
      active-CED-4 mutants.

PMID- 9645479
TI  - Constitutive and inducible type 1 ribosome-inactivating proteins (RIPs) in
      elderberry (Sambucus nigra L.).
AB  - Two novel highly basic type 1 (single chain) ribosome-inactivating proteins
      (RIPs) with N-glycosidase activity have been found in elderberries (the fruits of
      Sambucus nigra L.). Mass spectrometry of these RIPs, which we named nigritins f1
      and f2, gave Mr values of 24095 and 23 565, respectively. Both proteins strongly
      inhibited protein synthesis in rabbit reticulocyte lysates but were inactive
      against plant ribosomes. Both nigritins have a similar topological activity on
      pBlueScript SK+ DNA as that displayed by dianthin 30. Nigritin f1 is a
      constitutive RIP since it is present in both green and mature intact elderberries
      at nearly the same proportion with respect to total fruit protein. By contrast,
      nigritin f2 is inducible and only appeared in mature intact elderberries.
      Elderberries also contain two isoforms of a basic nigrin equivalent to the
      recently found basic nigrin b in elder bark (De Benito et al., FEBS Letters 413
      (1997) 85-91). Our results indicate that probably not all plant RIPs exert the
      same biological function and that this may be determined by the physiological
      state of the tissue.

PMID- 9645480
TI  - N-copine: a novel two C2-domain-containing protein with neuronal activity
      regulated expression.
AB  - Neuronal activity is often associated with changes in gene expression. By a two
      dimensional cDNA-display system, restriction landmark cDNA scanning, we
      identified a novel gene whose expression in the hippocampus was up-regulated by
      kainate stimulation. The mRNA expression was detected only in brain and up
      regulated by the stimulation evoking CA3-CA1 long-term potentiation. The encoded
      protein contains two copies of C2-domain, known as the Ca2+-binding domain of PKC
      gamma, and shows 49% identity with human copine I. We designated this protein N
      copine (neuronal-copine). N-copine may have a role in synaptic plasticity.

PMID- 9645481
TI  - Identification of two forms of the gamma subunit of G protein, gamma10 and
      gamma11, in bovine lung and their tissue distribution in the rat.
AB  - Two forms of the gamma subunit of G protein were purified from bovine lung, and
      were identified as gamma10 and gamma11 by analyses of partial amino acid
      sequences and reactivity with specific antibodies. The N-terminal amino acid
      residue of gamma11 was an unmodified Pro2, and the purified gamma11 was freed
      from beta even under non-denaturing conditions. Western blots with specific
      antibodies against gamma10 and gamma11 showed that both gamma subunits are
      present in a variety of tissues in the rat, with a particular abundance of
      gamma11 in the platelets.

PMID- 9645482
TI  - Cationic uncouplers of oxidative phosphorylation are inducers of mitochondrial
      permeability transition.
AB  - To determine whether cationic uncouplers of oxidative phosphorylation induce
      permeability transition in mitochondria, the effects of the divalent cationic
      sulfhydryl cross-linker copper-o-phenanthroline (Cu(OP)2) and the cyanine dye tri
      S-C4(5) on rat liver mitochondria were examined. Like Ca2+, they accelerated
      mitochondrial respiration with succinate and induced mitochondrial swelling when
      inorganic phosphate (Pi) was present in the incubation medium. The acceleration
      of respiration and swelling were inhibited by the SH-reagent N-ethylmaleimide,
      and by the specific permeability transition inhibitor cyclosporin A (CsA). In
      addition, these cations, like Ca2+, induced release of ADP entrapped in the
      mitochondrial matrix space, and the morphological change of mitochondria induced
      by these cations was essentially the same as that induced by Ca2+. It is
      concluded that the uncoupling actions of Cu(OP)2 and tri-S-C4(5) are due to
      induction of permeability transition in the inner mitochondrial membrane.

PMID- 9645483
TI  - Hydroxyl radicals are involved in the oxidation of isolated and cellular DNA
      bases by 5-aminolevulinic acid.
AB  - 5-Aminolevulinic acid (ALA) is a heme precursor, pathological accumulation of
      which is associated with liver cancer. We show that the reactive oxygen species
      produced upon ALA metal-catalyzed oxidation promote the formation of several
      radical-induced base degradation products in isolated DNA. The distribution of
      modified bases is similar to that obtained upon gamma irradiation. This
      observation strongly suggests the involvement of hydroxyl radicals in the ALA
      mediated DNA damage. Increased levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine and
      5-hydroxy-2'-deoxycytidine in organ DNA of rats chronically treated with ALA were
      observed. This is strongly suggestive of the implication of hydroxyl radicals in
      the ALA-induced degradation of cellular DNA.

PMID- 9645484
TI  - Vitamin C attenuates nitrate tolerance independently of its antioxidant effect.
AB  - In LLC-PK1 kidney epithelial cells, a 5-h pretreatment with glyceryl trinitrate
      (GTN) resulted in substantial desensitization of the intracellular cyclic GMP
      response to a subsequent 10-min challenge with GTN (1 microM). GTN-tolerant cells
      were fully sensitive to the spontaneous nitric oxide (NO) donor spermine NONOate,
      which does not require enzymatic bioactivation. Cyclic GMP stimulation by GTN was
      up to 3.1-fold higher when vitamin C (1-10 mM) was present during the
      pretreatment period. In contrast, other oxygen radical scavengers such as tiron
      or dimethylsulfoxide and the NO scavenger PTIO left tolerance induction
      unaltered. Together, our results suggest that reactive oxygen species or NO do
      not contribute to the development of nitrate tolerance. Tolerance reduction by
      vitamin C may be due to a stabilizing effect on enzymes involved in the
      bioconversion of GTN to NO.

PMID- 9645485
TI  - Dipeptidyl peptidase IV (DP IV, CD26) is involved in regulation of DNA synthesis
      in human keratinocytes.
AB  - Various studies have shown that the membrane ectoenzyme dipeptidyl peptidase IV
      (DP IV, CD26), expressed on T, NK, and B cells in the human immune system, is
      involved in the regulation of DNA synthesis and cytokine production. Here, we
      clearly demonstrate that this enzyme is highly expressed also on human epidermal
      foreskin and split-skin keratinocytes and that the specific DP IV inhibitors
      Lys[Z(NO2)]-thiazolidide, Lys[Z(NO2)]-pyrrolidide inhibit the enzymatic activity
      as well as the DNA synthesis of these cells. These data demonstrate that CD26
      plays a role also in regulation of DNA synthesis of epidermal keratinocytes and
      that the enzymatic activity is required for mediating these effects.

PMID- 9645486
TI  - Cloning and expression of the gene for a vanadium-dependent bromoperoxidase from
      a marine macro-alga, Corallina pilulifera.
AB  - The cDNAs for a vanadium-dependent bromoperoxidase were cloned from a marine
      macro-alga, Corallina pilulifera. The open reading frame of one clone (bpo1)
      encoded a protein of 598 amino acids with a calculated molecular mass of 65312 Da
      in good agreement with that of 64 kDa determined for the native enzyme. The
      deduced amino acid sequence coincided well with partial sequences of peptide
      fragments of the enzyme. From the same cDNA library we also isolated another cDNA
      clone (bpo2) encoding a protein of 597 amino acids with an identity of about 90%
      to BPO1, suggesting a genetic diversity of the bromoperoxidase gene of C.
      pilulifera growing in a relatively narrow area. The carboxy-terminal 123 residues
      of the enzyme (BPO1) showed an identity of 45% to that of the marine macro-alga
      Ascophillum nodosum. The homology search of the sequences of bromoperoxidases
      from C. pilulifera (this study) and A. nodostum, and chloroperoxidase from the
      fungus Curvularia inaequalis indicated highly conserved sequences PxYxSGHA and
      LxxxxAxxRxxxGxHxxxD. Furthermore, it was found that the histidine residue
      directly bound to vanadium, other residues building up the metal center and
      catalytic histidine residue forming the active site of the chloroperoxidase from
      C. inaequalis are conserved in the primary structure of the bromoperoxidase from
      C. pilulifera. The cloned hpol was introduced into Escherichia coli, and the
      expressed PO1 was purified from the recombinant strain. The N-terminal amino acid
      sequence of the purified BPO1 was identical to the deduced sequence from the cDNA
      except the N-terminal methionine.

PMID- 9645487
TI  - Two immunoglobulin-like domains of the Z-disc portion of titin interact in a
      conformation-dependent way with telethonin.
AB  - The giant muscle protein titin/connectin plays a crucial role in
      myofibrillogenesis as a molecular ruler for sarcomeric protein sorting. We
      describe here that the N-terminal titin immunoglobulin domains Z1 and Z2 interact
      specifically with telethonin in yeast two-hybrid analysis and protein binding
      assays. Immunofluorescence with antibodies against the N-terminal region of titin
      and telethonin detects both proteins at the Z-disc of human myotubes. Longer
      titin fragments, comprising a serine-proline-rich phosphorylation site and the
      next domain, do not interact. The interaction of telethonin with titin is
      therefore conformation-dependent, reflecting a possible phosphorylation
      regulation during myofibrillogenesis.

PMID- 9645488
TI  - Ganglioside GM2 is substrate for a sialidase in MDCK cells.
AB  - GM1 ganglioside carrying a fluorescent fatty acid in substitution of the natural
      one, has been administered to cultured Madin-Darby canine kidney (MDCK) cells for
      different pulse times (0.5-24 h), and its metabolic fate was followed. The
      fluorescent GM2, asialo-GM2, asialo-GM1 and ceramide were the only detectable
      metabolites. The complete absence of fluorescent GM3 is consistent with the
      presence in these cells of a sialidase working on GM1 and GM2 gangliosides. After
      treatment of the cells with chloroquine the fluorescent GM1 remained essentially
      undegraded, indicating a catabolic processing at lysosomal level.

PMID- 9645489
TI  - A role of neutrophils in the down-regulation of IL-6 and CD14 following
      hemorrhagic shock.
AB  - Hemorrhagic shock (HS) followed by resuscitation has been shown to initiate a
      series of events, including local cytokine production and PMN accumulation. To
      determine whether PMN are involved in the regulation of IL-6 expression in the
      liver or lungs, IL-6 mRNA levels were measured in rats made neutropenic by
      vinblastine pretreatment prior to HS. IL-6 mRNA levels were determined at 4 or 24
      h following resuscitation from shock. Vinblastine alone in normal rats or sham
      treated rats had no effect at 4 or 24 h. Vinblastine pretreatment had no effect
      on the HS-induced increase in IL-6 mRNA at 4 h but dramatically increased levels
      in both liver and lung at 24 h. Peripheral PMN counts were reduced by 95% in all
      vinblastine-treated animals. Similar changes seen in CD14 mRNA expression
      indicate that these effects are not limited to IL-6. These data show that normal
      PMN levels are not needed for induction of IL-6 and CD14 in HS, and suggest that
      PMN accumulation down-regulates the expression of these genes.

PMID- 9645490
TI  - Dithiocarbamates enhance tumor necrosis factor-alpha production by rabbit
      alveolar macrophages, despite inhibition of NF-kappaB.
AB  - The tissue-fixed macrophage (Mphi) plays a key role in coordinating the excessive
      inflammatory response following shock or sepsis. Reactive oxygen intermediates
      have been recently described as second messengers involved in signal transduction
      in these cells, including the activation of the transcription factors NF-kappaB
      and AP-1. The dithiocarbamates are potent antioxidants that inhibit NF-kappaB
      activation. We postulated that dithiocarbamates would inhibit Mphi activation via
      inhibition of NF-kappaB. Rabbit alveolar Mphi were obtained by bronchoalveolar
      lavage and exposed to either pyrrolidine dithiocarbamate (PDTC) or diethyl
      dithiocarbamate (DDTC) followed by stimulation with LPS (10 ng/mL). Supernatants
      were analyzed for TNF and prostaglandin E2, (PGE2) and F2-isoprostane (ISP), a
      marker of membrane lipid peroxidation, production at 18 h. PDTC and DDTC
      significantly enhanced production of TNF while inhibiting PGE2 and ISP production
      compared with LPS alone (p < .05). Northern blots revealed increased mRNA for TNF
      after pretreatment with PDTC, compared with LPS alone. Western blots and
      oligonucleotide gel shifts of nuclear proteins revealed inhibition of NF-kappaB
      activation by both PDTC and DDTC. AP-1 activity was shifted to earlier time
      points by PDTC pretreatment. These results demonstrate transcriptional and
      functional enhancement of TNF production despite inhibition of NF-kappaB
      activation. This may be due in part to a loss of autocrine feedback inhibition by
      PGE2 and enhancement of AP-1 activity. On the basis of these results, we conclude
      NF-kappaB may be necessary but, in contrast to prior analyzes, is not sufficient
      for optimal response of the alveolar Mphi to endotoxin.

PMID- 9645491
TI  - Effect of melatonin on activated macrophage TNF, IL-6, and reactive oxygen
      intermediates.
AB  - Melatonin has recently been investigated as a biological response modifier in
      sepsis and hypovolemic shock. Although melatonin is reported to influence a
      variety of inflammatory and immune responses, evidence supporting its effects on
      important macrophage-derived mediators is incomplete. This study was designed to
      determine whether melatonin alters the release TNF, IL-6, and reactive oxygen
      intermediates by activated macrophages. TNF and IL-6 bioactivity in LPS
      stimulated Wistar rat alveolar macrophage and RAW 264.7 cell culture supernatants
      were unchanged by pretreatment with melatonin. Similarly, macrophage production
      of reactive oxygen intermediates, including H2O2 and superoxide anion, were
      unaffected by melatonin pretreatment. PMA-stimulated H2O2 production was
      determined in rat alveolar macrophages and RAW 264.7 cells. Superoxide anion
      generation was determined in the rat alveolar macrophage NR8383 cell line.
      Melatonin, at concentrations ranging from 10(-7) to 10(-4) M, does not alter LPS
      stimulated TNF and IL-6, or PMA-stimulated H2O2 and superoxide anion production
      by the macrophage populations studied. These observations are in contrast to
      previous reports. Further studies are necessary to determine whether melatonin
      indirectly influences macrophage function by actions on nonmacrophage cell
      populations.

PMID- 9645492
TI  - Platelet-activating factor is a key mediator of pulmonary vasoconstriction and
      bronchoconstriction after antigen challenge in the perfused sensitized rabbit
      lung.
AB  - Exposure of sensitized perfused rabbit lungs to human O-N type erythrocytes leads
      to pulmonary vasoconstriction and bronchoconstriction. To investigate whether
      platelet-activating factor (PAF) is a mediator of pulmonary vasoconstrictive and
      bronchoconstrictive responses after antigen challenge, we administered antigenic
      erythrocytes after the administration of PAF antagonist (.1 mg/kg; CV6209).
      Pulmonary arterial and airway pressures significantly increased after antigen
      challenge in the sensitized rabbit lungs, but not in the nonsensitized rabbit
      lungs. CV6209 significantly inhibited these pulmonary vasoconstrictive and
      bronchoconstrictive responses after antigen challenge. We concluded that PAF, at
      least in part, plays an important role in pulmonary vasoconstriction and
      bronchoconstriction after antigen challenge in rabbits.

PMID- 9645493
TI  - Effect of NG-nitro-L-arginine methyl ester on testicular blood flow and serum
      steroid hormones during sepsis.
AB  - Production of nitric oxide (NO) via NO synthase (NOS) has been implicated in the
      regulation of steroidogenesis in normal physiology and septic pathophysiology.
      The hypothesis that blockade of NOS by NG-nitro-L-arginine methyl ester (L-NAME)
      would affect testicular blood flow and circulating levels of steroid reproductive
      hormones was tested. Male Sprague-Dawley rats (350-450 g) were randomized to
      septic and nonseptic groups. Sepsis was induced with an intraperitoneal (i.p.)
      injection of a cecal slurry (200 mg/kg in 5 mL 5% dextrose in water (D5W)) in
      rats, while nonseptic rats received only sterile D5W. The rats (n = 6 per group)
      were catheterized in the jugular vein, left ventricle (via right carotid artery),
      and tail artery to determine blood flow and systemic hemodynamics and to collect
      blood at 24 h after induction of sepsis/sham sepsis. After baseline (24 h post
      cecal slurry challenge) measurement, L-NAME (.50 mg/ kg x min) was infused
      through the jugular vein for 10 min, blood flow was determined using a
      radioactive microsphere technique, and blood samples were collected. The serum
      concentrations of corticosterone, progesterone, and testosterone were determined
      using radioimmunoassay. Plasma concentrations of NO byproducts (NOx) were
      determined using the Greiss reaction. After 24 h, heart rate, testicular blood
      flow, and NOx levels were significantly increased, whereas the serum
      concentration of testosterone was significantly decreased in the septic group as
      compared with the nonseptic group. However, serum concentrations of progesterone
      and corticosterone at 24 h after induction of sham-sepsis or sepsis were not
      statistically different. Infusion of L-NAME significantly reduced the testicular
      blood flow and serum NOx levels in septic rats as compared with their baseline
      values. The administration of L-NAME significantly increased the concentration of
      testosterone in nonseptic and septic rats as compared with their respective basal
      values. However, testosterone levels in septic rats were still significantly
      lower than in nonseptic rats. The results of this study indicate that the
      synthesis of NO through NO synthase may play a role in the regulation of
      testicular blood flow and the serum levels of testosterone, associated with
      chronic peritoneal sepsis in the rat.

PMID- 9645494
TI  - Paradoxical changes in organ blood flow after arginase infusion in the non
      stressed rat.
AB  - Arginine (ARG) is the precursor of nitric oxide (NO), a potent vasodilator.
      Arginase (ASE) is released following hepatocellular damage, resulting in low
      plasma ARG levels. The effect of ASE infusion on hemodynamics was studied. Rats
      received a 20 min ASE or saline infusion, and systemic hemodynamics and organ
      blood flow were studied, at 30 and 270 min, using radiolabeled microspheres.
      Compared with control, ASE resulted (30 min) in 1) undetectable ARG levels; 2)
      higher mean arterial pressure and total peripheral resistance (both p < .05); 3)
      higher blood flow to the heart, kidneys, stomach, small intestine (all p < .05),
      and spleen (p < .001); and 4) lower vascular resistance in the heart, kidneys,
      stomach, and small intestine (all p < .05) and in the spleen (p < .005). At 270
      min, ASE rats had similar organ blood flow and higher nitrate levels in urine and
      plasma (both p < .05) compared with control. We conclude that ASE reduces ARG
      levels with simultaneous increase in mean arterial pressure and total peripheral
      resistance. Higher nitrate production, suggesting higher NO formation in the
      presence of low ARG plasma levels, is paradoxical but could explain the higher
      blood flow in some organs. The increased total peripheral resistance during
      higher nitrate formation suggests regional differences in dependency of NO
      production on plasma ARG levels.

PMID- 9645495
TI  - Effect of liposome-encapsulated hemoglobin on the development of endotoxin
      induced shock in the rat.
AB  - Liposome-encapsulated hemoglobin (LEH) is an experimental oxygen-carrying
      resuscitation fluid. Because LEH is cleared from the circulation primarily by the
      reticuloendothelial system, its effect on the development of sepsis remains a
      major concern. Thus, the present study aimed to evaluate whether LEH modifies
      consequences of endotoxemia in the conscious normovolemic rat. LEH infusion at
      10% of estimated blood volume (n = 10) did not affect mortality (30%, p < .05)
      and serum tumor necrosis factor-alpha levels (6204 +/- 414, p < .05) induced by
      3.6 mg/kg Escherichia coli endotoxin administered (intravenous bolus) 22 h later.
      In contrast, when a shorter LEH-endotoxin time interval (<12 h, n = 10) or a
      higher dose of endotoxin (14.4 mg/kg, n = 20) was tested, LEH enhanced endotoxin
      induced mortality (90% and 100%, respectively, p < .05) and broadened serum tumor
      necrosis factor-alpha response without modifying its peak levels. LEH (n = 20)
      did not exacerbate the endotoxin-induced tachycardia, leukopenia, and
      thrombocytopenia. Therefore, in this model, the effect of LEH on endotoxin
      induced responses was dependent on the time interval between LEH and endotoxin
      administration as well as the endotoxin dose. The clinical relevance of these
      results should be further investigated.

PMID- 9645496
TI  - Time-dependent cardiovascular and inflammatory changes in acute endotoxemia.
AB  - The pathophysiology of experimental acute endotoxemia is a complex process
      involving both cardiovascular dysfunction and an inflammatory response. We have
      examined the correlation in hemodynamic changes and the pulmonary inflammatory
      response after lipopolysaccharide (LPS) administration with respect to time.
      Importantly, we have measured the lung and plasma levels of nitric oxide (NO)
      over time, as well as rapid generation of lung superoxide after LPS
      administration. In anesthetized rats given a bolus injection of LPS (10 mg/kg
      intravenously, from Salmonella enteritidis), mean arterial blood pressure dropped
      by 63-70% within 15 min, and cardiac output fell by 57-63% within 20 min compared
      with saline controls. Mean arterial blood pressure recovered slightly but was
      still 51, 30, and 25% less than that of saline controls 45, 105, and 165 min
      after LPS administration, respectively. Cardiac output remained depressed
      throughout the experimental period and was 35% lower than in saline controls 165
      min after LPS treatment. There was a small increase in plasma nitrite/nitrate as
      an index of plasma NO production after 45 min and a 10-fold increase 165 min
      after LPS addition compared with controls, strongly suggesting that NO mediates
      the hypotension that occurs 165 min after LPS administration. Lung NO production
      increased twofold 105 min after LPS administration and remained higher than in
      saline controls. Histological sections showed that there was fluid accumulation
      and alveolar collapse in the lung 45 min after LPS, whereas after 165 min, there
      was extensive tissue damage and increased leukocyte accumulation compared with
      controls. These results suggest that there was no correlation between early (1 h)
      tissue damage and NO production. We found an increase in lung superoxide
      generation 15 min after injection of LPS that coincided with the alterations in
      cardiovascular function. These results suggest that early lung tissue damage
      and/or hemodynamic changes may be due to superoxide generation from the lung.

PMID- 9645497
TI  - Trauma-hemorrhage activates signal transduction pathways in mouse splenic T
      cells.
AB  - Severe impairment in the functions of immune-competent cells has been observed
      following trauma and hemorrhage. Inappropriate release of cytokines during trauma
      and hemorrhagic shock disrupt T lymphocyte functions and enable cells to activate
      genes whose products are detrimental for maintaining a much-needed humoral and
      cell-mediated immunity. The intracellular events for gene activation are mediated
      by cytoplasmic transcription factors present as nascent (signal transducer and
      activator of transcription 1 (STAT 1)) or as a complex (nuclear factor kappaB (NF
      kappaB)). Receptor-initiated phosphorylation activates these transcription
      factors prior to their nuclear translocation and binding to cognate DNA
      sequences. Because T cell functions are critical to efficient functioning of the
      immune system, we investigated whether expression of transcription factors, STAT1
      and NF-kappaB, is perturbed in splenic T cells following trauma and hemorrhage.
      To study this, enriched T cells harvested from spleens (pooled from three or four
      mice per group) of sham, trauma (consisting of midline laparotomy), sham+trauma,
      hemorrhage (blood pressure maintained at approximately 30 mmHg for 90 min
      followed by adequate fluid resuscitation), and trauma+hemorrhage groups at 16-18
      h after surgical procedure were probed for signal expressions in the presence and
      absence of interferon-gamma using electrophoretic mobility shift and Western
      immunoblot assay procedures. Hemorrhage with or without trauma induced activation
      of Janus kinase 1, STAT1, and NF-kappaB in T cells. Stimulation of T cells with
      interferon-gamma led to activation of all these signals in all groups including
      experimental controls. STAT1 activation was accompanied by Janus kinase 1
      phosphorylation, whereas NF-kappaB activation was mediated by phosphorylation and
      rapid degradation of IkappaBalpha. These studies demonstrate that hemorrhagic
      shock, with or without laparotomy, is sufficient to induce activation of
      transcription factors in splenic T cells. Thus, attempts to prevent the
      activation of transcription factors following hemorrhage by pharmacologic means
      might be helpful for maintaining cell-mediated immunity under these conditions.

PMID- 9645498
TI  - Pulmonary hypertension and reduced cardiac output during inhibition of nitric
      oxide synthesis in human septic shock.
AB  - It has been suggested that inhibitors of nitric oxide synthesis are of value in
      the treatment of hypotension during sepsis. In this pilot study, we examined the
      effects of inhibition of nitric oxide synthesis by continuous infusion of
      N(omega)-nitro-L-arginine methyl ester (L-NAME) at 1.5 mg/kg/h in a patient with
      severe septic shock. L-NAME produced a rise in mean arterial blood pressure and
      systemic vascular resistance; catecholamine infusion could be reduced. Parallel
      to these findings, there was a 50% reduction in cardiac output and a 5-fold rise
      in pulmonary vascular resistance, which resulted in severe pulmonary hypertension
      after 3 h of L-NAME infusion, for which the infusion had to be stopped. Following
      the termination of L-NAME infusion, pulmonary artery pressure and blood pressure
      returned to baseline values, although pulmonary and systemic vascular resistance
      remained elevated for several hours. We conclude that nitric oxide appears to
      play a role in the cardiovascular derangements during human sepsis. Inhibition of
      nitric oxide synthesis with L-NAME can increase blood pressure and systemic
      vascular resistance. However, reduced cardiac output and pulmonary hypertension
      are possible side effects of continuous NO synthase inhibition. These side
      effects necessitate careful monitoring and may hinder the clinical application of
      NO synthase inhibitors.

PMID- 9645499
TI  - Lipid metabolism: new approaches to old problems.

PMID- 9645500
TI  - Defects of lipoprotein metabolism in familial combined hyperlipidaemia.
AB  - Familial combined hyperlipidaemia is the most common inherited hyperlipidaemia
      and is found in up to 10% of patients with premature myocardial infarction. The
      genetic and metabolic bases of the disorder have not yet been defined. This
      review discusses the important advances in the past year in our understanding of
      the different metabolic pathways contributing to the pathogenesis of familial
      combined hyperlipidaemia.

PMID- 9645501
TI  - Heterogeneity of apolipoprotein B-100-containing lipoproteins: what we have
      learnt from kinetic studies.
AB  - Apolipoprotein B-100-containing lipoprotein assembly is dependent on the
      successive addition of triglyceride by microsomal transfer protein. Assembly may
      end at this point and the lipoprotein secreted or it may continue with the bulk
      addition of triglyceride by an unknown transfer process. These steps are
      independently regulated and result in the secretion of a spectrum of
      apolipoprotein B-100-containing particles. The production of small, dense LDL is
      determined by the type of VLDL secreted by the liver. Large, triglyceride-rich
      VLDL1 results in the formation of small, dense LDL through triglyceride exchange
      and subsequent hydrolysis. Small, dense LDL are cleared from plasma relatively
      slowly and tend to accumulate in the circulation where they exert their
      atherogenic effects.

PMID- 9645502
TI  - Structure and function of the plasma phospholipid transfer protein.
AB  - Recent cloning and sequencing of plasma phospholipid transfer protein
      complementary DNA revealed that phospholipid transfer protein belongs to the
      lipid transfer/lipopolysaccharide binding protein family that includes the
      cholesteryl ester transfer protein, the bactericidal permeability increasing
      protein and the lipopolysaccharide-binding protein. In addition to structural
      similarities, members of the lipid transfer/lipopolysaccharide-binding protein
      family might share some common functional properties, and recent studies
      demonstrated that phospholipid transfer protein can act in several distinct
      metabolic processes. In particular, the molecular transfer of phospholipids,
      unesterified cholesterol, alpha-tocopherol and lipopolysaccharides by
      phospholipid transfer protein suggests that it might be involved both in
      lipoprotein metabolism and in antimicrobial defence, resulting in a growing
      interest in this protein.

PMID- 9645503
TI  - The role of hepatic lipase in lipoprotein metabolism and atherosclerosis.
AB  - In addition to its traditional role in the hydrolysis of lipoprotein
      triglycerides and phospholipids, recent studies have implicated hepatic lipase in
      other aspects of cellular lipid and/or lipoprotein metabolism and
      atherosclerosis. Hepatic lipase may serve as a ligand that mediates the
      interaction of lipoproteins to cell surface receptors and/or proteoglycans as
      well as modulating aortic lesion development in different animal models. Over the
      past several years significant advances have been made in our understanding of
      new, alternative mechanisms by which hepatic lipase may modulate lipoprotein
      metabolism and the development of atherosclerosis in vivo.

PMID- 9645504
TI  - The lipolysis stimulated receptor: a gene at last.
AB  - The lipolysis stimulated receptor is a lipoprotein receptor that was initially
      described in 1992. In the presence of free fatty acids, the lipolysis stimulated
      receptor recognizes either apolipoprotein B or apolipoprotein E, and as a
      consequence, leads to the internalization and degradation of the lipoprotein
      particles. Its affinity is highest for those lipoproteins most susceptible to
      lipolysis, triglyceride-rich lipoproteins. Since the initial biochemical
      identification and description of the lipolysis stimulated receptor, several
      reports have been published by our group that provide circumstantial evidence for
      its role in vivo for the clearance of triglyceride-rich lipid particles. In this
      review, we bring the readers up-to-date on the evidence for the role of the
      lipolysis stimulated receptor in lipoprotein metabolism, as well as the recent
      developments in its molecular characterization.

PMID- 9645505
TI  - New insights into bile acid transport.
AB  - The enterohepatic circulation of bile acids is maintained by a series of membrane
      transport proteins. Recent studies of the cloned sodium bile acid cotransporters
      have provided new insights into their tissue expression, regulation, and their
      relationship to cholesterol homeostasis and human diseases such as primary bile
      acid malabsorption.

PMID- 9645506
TI  - Role of muscle in triglyceride metabolism.
AB  - It has long been recognized that skeletal muscle can contain modest stores of
      triglyceride and that this depot of fuel can make a major contribution to energy
      production during exercise. More recently, an adverse effect of muscle
      triglyceride has begun to be defined within the context of insulin resistance.
      Animal and clinical investigations have revealed a significant relation between
      increased muscle triglyceride and insulin resistance, at least among mostly
      sedentary individuals. These observations have stimulated the development, or at
      least the refinement, of new methodologies to assess this aspect of 'regional'
      fat deposition. In parallel, there has also been important new work designed to
      enable better understanding of the factors that regulate muscle triglyceride and
      to determine whether fatty acids taken up by skeletal muscle are oxidized or
      stored, and how these pathways might be either altered by the presence of insulin
      resistance or, in turn, contribute to the pathogenesis of insulin resistance.

PMID- 9645507
TI  - Cholesterol, endothelial function and cardiovascular disease.
AB  - Hypercholesterolaemia is associated with endothelial dysfunction and increased
      risk of atheromatous disease. Although endothelial dysfunction has been
      demonstrated early in the course of the disease process, it remains difficult to
      establish a causal relationship. Despite this, endothelial function has been used
      as a surrogate marker in small trials to identify and assess the effectiveness of
      therapeutic interventions to reduce cardiovascular mortality, before large scale
      clinical trials are undertaken. Recently, arterial stiffness has emerged as an
      independent risk factor for cardiovascular disease and may provide a link between
      hypercholesterolaemia, endothelial dysfunction, hypertension and stroke.

PMID- 9645508
TI  - Lipid metabolism.

PMID- 9645509
TI  - Nutrition and therapeutics.

PMID- 9645510
TI  - Genetics and molecular biology.

PMID- 9645511
TI  - Lipid metabolism.

PMID- 9645512
TI  - Hyperlipidemia and cardiovascular disease.

PMID- 9645513
TI  - Atherosclerosis: cell biology and lipoproteins.

PMID- 9645514
TI  - Therapy and clinical trials.

PMID- 9645515
TI  - Unicompartmental knee arthroplasty in middle-aged patients: a 2- to 6-year follow
      up evaluation.
AB  - Twenty-eight unicompartmental knee arthroplasties performed as an alternative to
      high tibial osteotomy or tricompartmental knee arthroplasty in patients under 60
      years of age were reviewed after 2 to 6 years of follow-up. The patient's age at
      the time of operation averaged 52 years. Using the Knee Society Score, 90% were
      rated good or excellent results in terms of function and pain relief. The average
      flexion angle obtained was 124 degrees, and the average postoperative alignment
      was 4 degrees of anatomic valgus for varus deformities and 8 degrees for valgus
      deformities. The average activity level according to the Tegner and Lysholm score
      slightly improved (preoperative, 2.3; follow-up, 2.7 points). Of the 28 knees, 9
      (32%) presented radiolucent lines about the tibial component and two had
      incomplete radiolucent lines at the bone-cement interface on the femoral side.
      There was no correlation between activity level and tibial radiolucent lines. Two
      revisions were performed because of loosening of the femoral component at the
      prosthesis-cement interface. One was converted to another unicompartmental
      arthroplasty and the other to a tricompartmental arthroplasty. One tibial
      component exhibited an asymptomatic slowly progressive radiolucency.
      Unicompartmental knee arthroplasty in middle-aged patients yields 2- to 6-year
      results competitive with osteotomy but inferior to tricompartmental arthroplasty
      in terms of revision. The specific prosthetic design used in this series appeared
      to be vulnerable to femoral component loosening possibly because of constrained
      tibial topography and smooth tapered femoral fixation lugs.

PMID- 9645516
TI  - Unicompartmental arthroplasty: a long-term follow-up study.
AB  - Seventy-three consecutive unicompartmental knee arthroplasties (UKAs) using a
      Marmor-style non-metal-backed cemented tibial component were performed from 1975
      to 1990. Sixty-seven knees (58 patients) were evaluated with minimum 5-year
      follow-up (mean, 9.7 years; range, 5-20 years). Knee rating and patient function
      were assessed using the updated Knee Society scoring system. Survivorship was 91%
      at 5 years, 84% at 10 years, and 79% at 15 years. The mean knee rating for
      surviving implants was 91 (range, 48-100), and mean functional score was 77
      (range, 5-100). Survivorship and functional outcome were not affected by body
      habitus, age, gender, or tibial component thickness. UKA offers long-term relief
      of symptoms and excellent knee function in a high percentage of carefully
      selected patients with single compartment gonarthrosis.

PMID- 9645517
TI  - Complex primary and revision total knee arthroplasty using the condylar
      constrained prosthesis: an average 5-year follow-up.
AB  - The condylar constrained total knee arthroplasty was performed on 29 patients
      undergoing 33 procedures and were reviewed clinically and radiographically at an
      average follow-up of 5 years (range, 2-10 years). There were 21 women and 8 men.
      The average age at the time of surgery was 70 years (range, 32-84). Of the 16
      knees that were revision total knee arthroplasties, 8 had a previous infected
      total knee arthroplasty, and 17 knees had severe deformities requiring the use of
      the condylar constrained prosthesis. The patients were rated according to the
      Knee Society clinical and radiological evaluation protocol. Measurements of
      femoral and tibial component position were obtained as well as femoral tibial
      angle, patella position, and cement bone radiolucencies. All clinical
      measurements were made by an independent physical therapist. Clinical results
      revealed an improvement from an average preoperative knee score of 38 points to
      an average postoperative score of 86 points. The clinical results for 19 (58%)
      knees were excellent, 8 (24%) had a good result, 1 (3%) was fair, 2 (6%) were
      poor, and 3 (9%) were failures. The patients' average functional levels increased
      from 24 to 58. The final average flexion was 96 degrees. Three knees have been
      revised (9%). One was revised for recurrent infection, one for periprosthetic
      fracture, and one for mechanical loosening of the tibial component. There were no
      other knees with evidence of radiologic loosening. We conclude that the condylar
      constrained total knee prosthesis provides an acceptable solution for revision
      and complex primary total knee replacements at an intermediate follow-up term of
      5 years.

PMID- 9645518
TI  - Can a total knee replacement prosthesis be made entirely of polymers?
AB  - We have prospectively studied 63 total knee replacements (TKR) in which the
      femoral component was polyacetal, and 138 TKRs in which the femoral component was
      conventional cobalt chrome. The tibial and patellar components were of ultrahigh
      molecular weight polyethylene (UHMWPE). Patients were followed-up for at least 10
      years. In the polyacetal group, a number of patients have died or have been
      revised, for reasons unrelated to the presence of polyacetal. There were no
      instances of femoral component fracture, nor failure by wear. One postmortem
      specimen, retrieved at 9 years after surgery, showed no measurable polyacetal
      wear and negligible HDP wear. The histology of tissue in contact with polyacetal
      was indistinguishable from that adjacent to polymethyl methacrylate and UHMWPE in
      the same knee. We believe that polyacetal could be used for the femoral component
      of a TKR and that a further trial should be undertaken.

PMID- 9645519
TI  - Femoral cement grading in total hip arthroplasty.
AB  - The current gold standard for primary total hip arthroplasty is a cemented
      femoral component combined with a porous-coated acetabular component. Barrack and
      colleagues described a femoral cement mantle grading system which is increasingly
      being used to evaluate surgical technique and to compare arthroplasty results.
      The immediate postoperative radiographs of 100 primary total hip arthroplasty
      cases from five community surgeons were assessed by three observers to evaluate
      the overall quality of cement technique, the interobserver variability in cement
      mantle grading, and specific characteristics of the grading system. All three
      observers agreed on the grading in only 73% of the x-rays (anteroposterior view,
      69%; lateral view, 77%). Compared with reports in the literature from specialized
      hip arthroplasty centers, a very high proportion of the cases had grade C
      mantles. To gain a balanced perspective of the global effectiveness and longevity
      of cemented total hip arthroplasty it is important that follow-up studies be
      reported upon from representative cross sections of the orthopaedic community.

PMID- 9645520
TI  - Problems with the Rotaflex: a 10 year review of a rotating hinge prosthesis.
AB  - The results of the first 10-year review of the Rotaflex total knee prosthesis are
      presented. Loosening, fracture, implant failure, and damage to the extensor
      mechanism have been frequent findings. Of 25 implants reviewed, an arthrodesis
      has been performed in 4 patients and an amputation in 2. Surgery has been
      declined in a further 4 patients. A brace is required by 7 of 19 patients in whom
      the prosthesis has not been removed, and the results of surgery are considered
      poor in 13 of these 19 patients. With an overall complication rate of almost 80%,
      there would appear to be no place for this prosthesis despite its continued
      availability.

PMID- 9645521
TI  - Results of 1,000 Performance knees: cementless versus cemented fixation.
AB  - A total of 893 patients with 1,000 Performance total knee prostheses were
      retrospectively studied. The mean follow-up was 5.2 years. In 584 cases, the
      femoral and tibial components were implanted using cementless techniques, and in
      416 knees the femoral and tibial components were cemented. All patients received
      a cemented all polyethylene patellar replacement. Tibial bone density determined
      fixation type. The average age of patients with cementless fixation was 64.3
      years versus 76.2 years for patients with cemented implants. The average
      subjective and functional Knee Society scores were 91.2 and 90.1 for patients
      with cementless knees and 89.6 and 83.5 for those with cemented replacements. A
      surprising absence of osteolysis around screw fixation was noted, and at 5 years,
      there was 99% implant survival.

PMID- 9645522
TI  - Preoperative physical therapy in primary total knee arthroplasty.
AB  - In order to evaluate the efficacy of preoperative physical therapy for patients
      undergoing elective primary total knee arthroplasty, 10 patients completed 6
      weeks of physical therapy before surgery (PT group). Ten patients served as
      controls (C group). Subjects were tested at baseline (PT only), before surgery, 6
      weeks after surgery, and 3 months after surgery using the Hospital for Special
      Surgery knee rating scale, range of motion, thigh circumference, walking speed,
      Cybex II isokinetic knee flexion, and extension testing, and computed tomography
      scanning for cross-sectional muscle area. Hospital stay and need for physical
      therapy after inpatient rehabilitation were also compared. Physical therapy
      produced modest gains in isokinetic flexion strength in these severely arthritic
      knees but no difference in extension strength. The decrease in isokinetic
      strength after surgery was not affected by preoperative physical therapy. Muscle
      area did not decrease significantly for the PT group, but it did decrease for the
      C group after surgery. While postoperative strength differences could not be
      demonstrated, preoperative physical therapy preserved thigh muscle area after
      surgery. The clinical significance of this finding is uncertain. Consequently,
      this study failed to support the routine use of preoperative physical therapy in
      knee replacement surgery.

PMID- 9645523
TI  - Bone loss around 2 different types of hip prostheses.
AB  - Dual energy x-ray absorptiometry (DXA) allows the measurement of bone mineral
      density (BMD) around an uncemented hip prosthesis. The aims of this study were:
      1) to determine the reproducibility of periprosthetic BMD measurements; 2) to
      delineate the time course of bone loss that occurs after insertion of a hip
      prosthesis; and 3) to compare the bone loss around two different types of hip
      prosthesis. We studied 20 patients: 11 had Bateman and 9 had porous-coated
      anatomic prostheses inserted. The mean bone loss in 20 patients between 6 and 52
      weeks after surgery was 6%. The greatest loss during this period was 18% and
      occurred from the proximal medial cortex. We conclude that measurement of
      periprosthetic bone mass by DXA is a precise technique. Bone loss was rapid in
      the first 6 months following total hip replacement. There was no difference in
      the bone loss occurring around the two prostheses studied.

PMID- 9645524
TI  - The forces in the distal femur and the knee during walking and other activities
      measured by telemetry.
AB  - The forces and moments in the shaft of a distal femoral replacement were measured
      by telemetry for a subject during different activities, and calculations were
      then made of the forces at the knee. The axial force showed a small peak at heel
      strike followed by two main peaks during stance. In level walking, the peak axial
      force was between 1,487 and 1,718 N (2.2-2.5 BW), the peak shear force was 269
      368 N (0.4-0.54 BW) directed anteriorly on the tibia, the peak axial torque was 7
      Nm internal, while the patellofemoral force was 466-571 N. The highest axial
      force was recorded for descending stairs (2.8 BW). Standing on one leg produced
      2.4 BW, while lying supine and raising the leg produced 1.7 BW. The data produced
      may resemble that of a normal subject, and has application to basic joint
      mechanics, to joint reconstruction, and to total knee replacement design and
      evaluation.

PMID- 9645525
TI  - Acetabular reconstruction with impacted morselized cancellous allografts in
      cemented hip arthroplasty: a histological and biomechanical study on the goat.
AB  - Bone defects in total hip arthroplasty revision surgery can be restored with
      different types of bone graft. The use of impacted morselized allograft chips in
      combination with cement is the treatment of our choice. To establish the
      incorporation capacity of the grafts and mechanical stability of the implant, an
      animal model in the goat was developed. An acetabular defect was created and
      restored with morselized grafts and a cemented cup. Postoperative performance of
      the reconstruction was followed both histologically and biomechanically.
      Histology showed that consolidation of the graft with the host bone bed had
      occurred within 3 weeks. In the following period a front of vascular sprouts
      infiltrated the graft. Graft resorption, woven bone deposition, and subsequent
      remodeling resulted in a new trabecular structure. This structure contained only
      scarce remnants of the original dead graft material. At the graft-cement
      interface, graft resorption and new bone formation had resulted in areas of
      direct vital bone-cement contact. Locally, a soft tissue interface was present.
      After longer follow-up periods, progressive interface formation and loosening of
      the cups were found in most animals. Mechanical testing showed that the stability
      of the reconstruction increased during the first 12 postoperative weeks.
      Thereafter, the stability decreased, probably by soft-tissue interface formation
      at the graft cement interface. We conclude that cemented morselized allografts
      have a high capacity to incorporate. Initial cup stability is adequate to provoke
      graft incorporation with decreasing stability after the incorporation process has
      been completed.

PMID- 9645526
TI  - Porous-coated versus grit-blasted surface texture of hydroxyapatite-coated
      implants during controlled micromotion: mechanical and histomorphometric results.
AB  - Hydroxyapatite (HA)-coated implants with porous-coated and grit-blasted surface
      textures were inserted bilaterally in a paired design into the medial femoral
      condyles of eight dogs for 16 weeks. The implants were weight-loaded and
      initially subjected to controlled micromotion of 500 microm during each gait
      cycle. Histology revealed that five implants in each group had bony anchorage,
      and the remaining implants were surrounded by fibrous tissue. Push-out testing
      showed no difference in shear stiffness and strength, while energy absorption for
      porous-coated implants was increased significantly by threefold. The HA coating
      delaminated on grit-blasted implants during push-out testing, whereas porous
      coated implants predominantly failed at the HA-tissue interface. Coverage,
      surface area, volume, and thickness of the HA coating were significantly reduced
      in vivo for porous-coated and grit-blasted implants. In conclusion, a plasma
      sprayed porous-coated implant surface seems to give better fixation not only of
      the HA-coating to the implant surface but also of the implant to the surrounding
      tissues in comparison to a grit-blasted implant surface. The HA coating was
      reduced more on fibrous-anchored than on bony-anchored implants, suggesting that
      micromotion accelerates resorption of HA. Resorbed HA coating was replaced by
      more bone on porous-coated implants than on grit-blasted implants, which suggests
      that fixation of porous-coated implants will be durable.

PMID- 9645527
TI  - Patellofemoral resurfacing. The value of instrumentation and design.

PMID- 9645528
TI  - Misconceptions about patellofemoral resurfacing in total knee replacement.

PMID- 9645529
TI  - Early osteolysis with Hylamer acetabular liners.
AB  - We reviewed 78 patients with Hylamer acetabular liners (DePuy-Dupont Orthopedics,
      Warsaw, IN), with a mean follow-up of 3.8 years (range, 2-6 years), for signs of
      osteolysis secondary to polyethylene wear. Nine patients (11.5%) showed
      osteolysis greater than 1 cm2. One patient had a greater trochanter fracture
      through a lytic area, one patient required a revision at 4 years for severe
      acetabular and femoral lysis with lesser trochanter fracture, and a second
      patient is awaiting revision.

PMID- 9645530
TI  - The use of femoral intramedullary nailing as an interim or salvage technique
      during complicated total hip replacement.
AB  - When performing a revision total hip replacement complicated by infection, severe
      osteolysis, comminuted periprosthetic fracture, and/or extensive bone loss, a
      single-stage procedure may not be feasible. This study reports four cases of
      femoral intramedullary nailing as an interim or salvage technique during
      complicated total hip replacement. This reconstruction provides axial and
      rotational stability of the femur while maintaining femoral alignment.
      Furthermore, this reconstruction facilitates early mobilization and
      rehabilitation of the patient. This interim reconstruction can be converted to a
      revision total hip replacement at a later time. Alternatively, the stabilized
      resection arthroplasty may serve as a salvage technique if further reconstruction
      is not indicated.

PMID- 9645531
TI  - Supracondylar femur fractures above an Insall-Burstein CCK total knee: a new
      method of intramedullary stem fixation.
AB  - Supracondylar femur fracture above a well-fixed posterior cruciate substituting
      prosthesis may not allow the use of standard fixation methods because of the
      closed nature of the femoral box. The Insall-Burstein Constrained Condylar Knee
      femoral prosthesis (Zimmer, Warsaw, IN) possesses a closed box and the capability
      of modular femoral stems. A retrieval device aids the utilization of the modular
      ability of the femoral prosthesis to gain intramedullary fixation of
      supracondylar femur fractures above a well-fixed femoral component allowing
      restoration of alignment, length, preinjury range of motion, and function.

PMID- 9645532
TI  - Prosthetic knee Candida parapsilosis infection.
AB  - We report a 77-year-old man who developed Candida parapsilosis infection
      following total knee arthroplasty. Knee joint effusion was noted 2 weeks after
      surgery, and repeated cultures of aspirated fluid established the diagnosis of
      Candida parapsilosis infection 4 weeks after surgery. Treatment consisted of
      debridement and lavage of the involved joint together with continuous irrigation
      with fluconazole for 4 weeks, followed by oral fluconazole for another 6 months.
      At 3 years follow-up, the patient was doing well and radiological examination of
      the affected knee showed a firm attachment of the prosthesis. We suggest that
      early identification of the causative organism followed by continuous irrigation
      and use of appropriate antifungal medication may prevent joint instability and
      spares the removal of the prosthesis.

PMID- 9645533
TI  - More recent advances in cementing technique...cement centrifugation and vacuum
      mixing have significantly improved the results of cement femoral implants.

PMID- 9645534
TI  - Analysis of inter-fragmentary movement as a function of musculoskeletal loading
      conditions in sheep.
AB  - It is well accepted that inter-fragmentary movement influences the fracture
      healing process. Small axial movement can stimulate callus formation whereas
      larger shear movement delays the healing process. It is, therefore, essential for
      optimal fracture healing to minimize shear and to control axial movement.
      Unfortunately, the complex gap movements are mostly unknown under the large
      variety of clinical as well as experimental conditions of fracture fixation. To
      further understand the complex interactions of musculoskeletal loading and inter
      fragmentary movements in bones and to reduce the need for animal experiments, a
      three-dimensional (3D) musculoskeletal model of the left hind limb of a sheep was
      developed. From 3D ground reaction forces and inverse dynamics, resultant joint
      loading was determined over a gait cycle. Muscle and joint contact forces were
      derived from an optimization routine and internal loads in the tibia and
      metatarsus from beam theory. Finally, inter-fragmentary movements were calculated
      from the bony loading condition and experimentally determined stiffness matrices
      of monolateral AISF external fixator constructs. Both the joint contact forces at
      the hip and gap movement of a mid-shaft tibial fracture agree with in vivo data
      reported in the literature. The bones proved to be mainly axially loaded with
      slightly increasing shear forces toward their ends. The results suggest that
      inter-fragmentary movement of metatarsal fractures is fairly independent of the
      fracture location whereas the movement increases in proximal tibial fractures
      compared to those in the distal and diaphyseal tibia. Considerable shear movement
      was found for all locations and external fixator mountings. However, shear
      movement could be minimized with a cranio-lateral rather than a cranio-medial
      shift from the cranial fixator plane.

PMID- 9645535
TI  - Heat-induced changes in the mechanics of a collagenous tissue: pseudoelastic
      behavior at 37 degrees C.
AB  - The outcome of many clinical heat therapies depends on the post-treatment
      structural integrity of the tissue. Unfortunately, there are few data on heat
      induced changes in the mechanical properties of tissues due to temperature levels
      commonly achieved in laser, microwave, and radio-frequency-based modalities.
      Without such information, one cannot design optimal clinical protocols. Hence, we
      present new findings on the uniaxial stress strain behavior at 37 degrees C of a
      model collagenous tissue (chordae tendineae) both before and after thermal
      damage. This damage was induced via a variety of different thermo-mechanical
      loads: isothermal heatings at temperatures from 65 degrees C to 90 degrees C,
      durations of heating from 120 to 3600 s, and isotonic loads during heating from 0
      to 0.65 MPa. Our data reveal that chordae exhibit pseudoelastic responses both
      before and after heating, but the extensibility, hysteresis, and compliance all
      increase with increased thermal damage. Fortunately, these complex heat-induced
      changes in behavior can be parameterized using a single measure of the prior
      thermal damage. This will clearly simplify the requisite constitutive
      formulations.

PMID- 9645536
TI  - Validated computation of physiologic flow in a realistic coronary artery branch.
AB  - The pulsatile flow field in an anatomically realistic model of the bifurcation of
      the left anterior descending coronary artery (LAD) and its first diagonal branch
      (D1) was simulated numerically and measured by laser Doppler anemometry. The
      inlet velocity profiles used in the computer simulation and in the physical
      experiments were physiologically realistic. The computational geometric model was
      developed on the basis of a digitized arterial cast. The curvature of the LAD
      over the cardiac surface leads to axial velocity profiles which are slightly
      skewed towards the epicardial wall. Downstream of the bifurcation, a strong
      skewing occurs towards the flow divider walls as a result of branching. Locally,
      the wall shear stress component caused by the complex secondary velocity can be
      as high as the axial component. The wall shear stress representation from a cell
      based perspective exhibits low shear stress and large deviation from the time
      averaged shear stress direction during systole. In diastole, the instantaneous
      wall shear stress direction nearly corresponds to the mean direction. The
      comparison of computed and measured axial velocity results shows generally good
      agreement. In contrast to computed flow patterns in simpler geometries
      constructed from cylindrical tubes, the flow field is found to be smoother,
      presumably reflecting the adaptation of the vascular contour to the contained
      flow.

PMID- 9645537
TI  - Compliance mismatch may promote graft-artery intimal hyperplasia by altering
      suture-line stresses.
AB  - The role of graft-artery compliance mismatch in the development of distal
      anastomotic intimal hyperplasia (DAIH) is not yet resolved. Although DAIH
      develops at all surgically created anastomoses, increased compliance mismatch
      does not lead to greater hyperplasia formation in end-to-end anastomoses, but in
      end-to-side anastomoses, it leads to a profound increase in hyperplasia. The
      current study was undertaken to determine whether suture-induced anastomotic
      stresses could explain these findings. A large strain finite element analysis of
      vascular wall mechanics was performed to compare the influence of compliance
      mismatch on intramural stresses in end-to-end versus end-to-side anastomoses. A
      novel modelling approach was implemented which includes suture-induced stress
      concentrations. End-to-end and end-to-side graft-artery simulations were executed
      using (1) artery (compliance = C = 0.44% kPa(-1)), (2) vein (C = 0.33% kPa(-1)),
      and (3) Dacron (C = 0.14% kPa(-1)) grafts. Residual stresses due to axial tension
      were included and the anastomoses were statically inflated to 13.3 kPa (100
      mmHg). Elevated intramural stresses were found to exist at both the end-to-end
      and end-to-side graft-artery junctions; however, in the end-to-end anastomosis,
      the maximum anastomotic stress was not a function of the graft compliance,
      whereas in the end-to-side anastomosis, the maximum stress was a strong function
      of graft compliance. For the 45 degree end-to-side geometry considered in this
      study, the maximum anastomotic stress concentration obtained using a stiff Dacron
      graft was more than 40% greater than that obtained using a compliant artery
      graft. In the end-to-end anastomosis, the Dacron graft led to a less than 5%
      increase in maximum stress over the artery graft. Therefore, increased compliance
      mismatch increases stresses and promotes DAIH in end-to-side junctions, but, it
      has little influence on either stresses or DAIH in end-to-end junctions. Thus,
      the proliferative influence of increased compliance mismatch on suture-line
      hyperplasia in end-to-side anastomoses can be explained by the resulting increase
      in intramural stresses. In addition, since high stresses were found in both
      geometries, elevated suture-line intramural stresses may be an important
      proliferative stimulus for intimal hyperplasia formation in all vascular
      reconstructions.

PMID- 9645538
TI  - Standard mechanical energy analyses do not correlate with muscle work in cycling.
AB  - The goal of this study was to assess the utility of experimental methods to
      quantify mechanical energy expenditure (MEE) in human movement. To achieve this
      goal, a theoretical model of steady-state cycling driven by individual muscle
      actuators was used to produce two distinct pedal simulations. The simulations
      yielded the same pedaling rate and power output, but one reduced the MEE by
      avoiding eccentric muscle contractions. Contractile element force and length
      change in the individual muscles was used to quantify the total positive and
      negative work produced by the muscles. Three methods using external measurements
      were applied to the simulated movement. The three methods to quantify MEE were
      based on: (1) segment kinematic measurements, (2) work done by total joint powers
      and (3) intercompensated joint powers, i.e. negative work from one joint is
      transferred to an adjacent joint where energy is being generated (positive work)
      via biarticular muscles. The results showed that none of the MEE analyses were
      correlated to the MEE of the individual muscles, with errors reaching 40%. Errors
      were mainly attributed to the inability of the MEE methods to account for co
      contractions of antagonistic muscle groups. This phenomenon occurred primarily
      when one muscle generated force during activation while the antagonist generated
      force during deactivation.

PMID- 9645539
TI  - A method to determine the 3-D stiffness of fracture fixation devices and its
      application to predict inter-fragmentary movement.
AB  - Inter-fragmentary movement considerably influences the fracture healing process.
      Large shear movement delays while moderate axial movement stimulates the healing
      process. To be able to control the mechanical situation at a fracture site and to
      achieve optimal bony healing it is essential to understand the relationship
      between inter-fragmentary movement, bony loading and fixation stiffness. A 6 x 6
      stiffness matrix is introduced which completely describes the linear relationship
      between the 6 inter-fragmentary movements and the resulting bony loading (3
      forces and 3 moments). Further, it is illustrated that even in relatively stiff
      external fixateur constructs simple axial loading of the bony fragments leads to
      complex inter-fragmentary movement. When the 3-D stiffness description is
      multiplied by the load state in sheep tibiae, movements similar to those measured
      in vivo are calculated. The relationship between axial compression and medio
      lateral or dorso-ventral shear varies depending on the mounting plane of the
      external fixateur. The authors conclude that a single value is not sufficient to
      describe the mechanical relationship between inter-fragmentary movement and bony
      loading. Only a complete description of fixation stiffness allows prediction of
      inter-fragmentary movement and differentiation between various configurations of
      fixation devices and their potential for mechanically promoting bony healing.

PMID- 9645540
TI  - In vivo knee joint loading and kinematics before and after ACL transection in an
      animal model.
AB  - Osteoarthritis (OA) is typically diagnosed in humans in its final stage when
      joint movement becomes painful. Clinical information about the onset and the
      mechanisms triggering the degenerative responses are virtually non-existent.
      However, research on animal models of experimental OA shows that joint
      adaptations associated with the onset of OA can be detected as early as two to
      four weeks following disruption of the normal joint mechanics. Transection of the
      anterior cruciate ligament (ACL) has been shown to cause OA-like symptoms in
      various animal models including the cat. However. the changes in joint loading
      responsible for the early tissue responses have not been quantified in vivo.
      Consequently, the relationship between abnormal joint loading and the onset of OA
      remains unknown. The purpose of this study was to quantify knee loading before
      and early after ACL transection in the cat. Knee mechanics were assessed by
      measuring patellar tendon forces, gastrocnemius forces, knee flexor and extensor
      EMGs, and hindlimb kinematics before and 5, 7, and 9 days following ACL
      transection in six experimental and two sham-operated animals. The knee mechanics
      were not affected by sham-surgery but the muscular forces. knee extensor EMGs,
      and knee range of motion were reduced following ACL transection compared to
      corresponding pre-intervention values. These results suggest that ACL transection
      causes a general unloading and changed kinematics of the knee. We speculate that
      the decrease in loading and the altered kinematics are responsible for the onset
      of biologic adaptations of the knee. Precise data about the local joint contact
      mechanics before and after ACL transection are now required to further relate the
      detailed changes in the knee mechanics to the early joint changes.

PMID- 9645541
TI  - A kinematic and kinetic analysis of the sit-to-stand transfer using an ejector
      chair: implications for elderly rheumatoid arthritic patients.
AB  - Twelve elderly female rheumatoid arthritis patients (mean age = 65.5 +/- 8.6 yr)
      were assessed rising from an instrumented Eser Ejector chair under four
      conditions: high seat (540 mm), low seat (450 mm), with and without the ejector
      mechanism operating. Sagittal plane motion, ground reaction forces, and vertical
      chair arm rest forces were recorded during each trial with the signals
      synchronised at initial subject head movement. When rising from a high seat,
      subjects displayed significantly (p < 0.05) greater time to seat off; greater
      trunk, knee and ankle angles at seat off; increased ankle angular displacement;
      decreased knee angular displacement; and decreased total net and normalised arm
      rest forces compared to rising from a low seat. When rising using the ejector
      mechanism, time to seat off and trunk and knee angle at seat off significantly
      increased, whereas trunk and knee angular displacement, and total net and
      normalised arm rest forces significantly decreased compared to rising unassisted.
      Regardless of seat height or ejector mechanism use, there were no significant
      differences in the peak, or time to peak horizontal velocity of the subjects'
      total body centre of mass, or net knee and ankle moments. It was concluded that
      increased seat height and use of the ejector mechanism facilitated sit-to-stand
      transfers performed by elderly female rheumatoid arthritic patients. However,
      using the ejector chair may be preferred by these patients compared to merely
      raising seat height because it does not necessitate the use of a footstool, a
      possible obstacle contributing to falls.

PMID- 9645542
TI  - Relation between the structural asymmetry of coronary branch vessels and the
      angle at their origin.
AB  - The relationship between the geometry of branch points on the left anterior
      descending coronary artery, and the morphometry of the proximal portions of the
      daughter vessels, was examined. The geometry at 23 branch points on 15 human
      hearts was derived from multiplane contrast angiograms, and the morphometry at 29
      sites along the daughter vessels was obtained from transverse sections using
      computerized techniques. The angle of the branch at which the daughter originated
      was positively correlated with the maximum thicknesses of the intima and media,
      and with their circumferential asymmetry. The results suggest that large branch
      angles may favor eccentric intimal thickening, a phenomenon which may predispose
      to lipid accumulation and atherosclerosis.

PMID- 9645543
TI  - Instantaneous moment arm determination of the cat knee.
AB  - The moment arm is an important parameter for calculating forces and pressures at
      a joint. Present techniques described in the literature are limited for joint
      studies in animals because of the invasive procedures required which destroy the
      joint integrity. This paper describes a new application of the instantaneous
      helical axis (IHA) for determination of the moment arm of the knee joint without
      compromising its integrity. Measurements based on the IHA technique are compared
      to an established technique using six cadaveric cat hind limbs. One experiment
      using the IHA technique was performed to demonstrate its application in situ. It
      was found that the moment arm determined by both techniques resulted in
      continuous estimations of similar magnitudes over the expected range of motion of
      the knee joint, although the IHA technique is sensitive to smoothing. A trend
      toward increasing moment arm as a function of increasing knee angle was observed
      in four of six specimens. The in situ experiment demonstrated the ability to use
      the IHA technique without compromising the integrity of the knee joint so that
      further histological, morphological, or topological information could be
      investigated.

PMID- 9645544
TI  - En bloc staining of bone under load does not improve dye diffusion into
      microcracks.
AB  - Microdamage accumulation in bone has been implicated in the pathogenesis of some
      bone fractures, and in implant loosening. Standard techniques for staining
      microcracks may not allow all cracks to be stained. We tested the hypothesis that
      crack closure in bone cortices after removal of a bending load may prevent
      diffusion of stain to sites of microcrack nucleation. Following cyclic loading,
      26 canine femurs were divided into a group stained en bloc while applying a four
      point bending load, and another group stained without an applied load. No
      differences in number or length of microcracks were observed, indicating that
      crack closure does not prevent diffusion of stain to the crack location. Staining
      under load is unnecessary.

PMID- 9645545
TI  - Global asymptotic stability of bone remodeling theories: a new approach based on
      non-linear dynamical systems analysis.
AB  - Mathematical tools for the analysis of nonlinear dynamical systems are applied to
      the study of stability of bone remodeling theories. As a practical application,
      the same problem studied by Harrigan and Hamilton (1992) and Cowin et al. (1994b)
      is analysed using these tools, and their findings on the necessary and sufficient
      conditions to ensure local asymptotic stability are easily confirmed. Using a
      general approach based on Lyapunov's method the same condition has been found to
      be necessary and sufficient also for the global asymptotic stability, thus
      confirming a result obtained by Harrigan and Hamilton (1994) by variational
      methods applied to finite-element models. The proof is based on the
      discretization of the spatial domain but the results for the continuum can be
      easily extrapolated.

PMID- 9645546
TI  - Schizophrenia and anteroventral thalamic nucleus: selective decrease of
      parvalbumin-immunoreactive thalamocortical projection neurons.
AB  - This study was designed to examine possible anatomical changes of thalamocortical
      circuits in schizophrenics. Previous immunocytochemical studies have shown that
      parvalbumin, a calcium-binding protein, occurs in thalamocortical projection
      neurons, but not in GABAergic interneurons in the anteroventral thalamic nucleus
      (AN). Using parvalbumin-immunocytochemistry we investigated the densities of
      thalamocortical projection neurons in the AN of schizophrenic cases (n = 12) and
      controls (n = 14). The densities of all neurons in the AN were estimated by Nissl
      staining. The majority of thalamocortical projection neurons in AN were
      identified by parvalbumin-immunoreaction. Significantly reduced densities of
      thalamocortical projection neurons were estimated in the right (P = 0.003) and
      left AN (P = 0.018) in schizophrenic subjects. The densities of all neurons in
      right and left AN were also diminished in schizophrenics; however, these
      decreases did not reach statistical significance. The reductions of parvalbumin
      positive thalamocortical projection neurons were not correlated with the length
      of disease, this finding supporting the neurodevelopmental etiology of structural
      abnormalities in schizophrenia.

PMID- 9645547
TI  - Reliability of medial temporal lobe volume measurements using reformatted 3D
      images.
AB  - The study assessed whether standardizing the angle of image display and
      controlling for head position in three planes affects the scan-rescan reliability
      of medial temporal lobe volume measures when very thin (1.5 mm) slices are used.
      Five volunteers were scanned two times on consecutive days. A three-dimensional
      MRI sequence acquired whole brain data in 1.4 mm thick coronal slices. The data
      were displayed as 1.5 mm thick images and were rated both in the originally
      acquired coronal plane, and after reformatting to correct for head tilt and
      display the brain in the coronal plane perpendicular to the long axis of the left
      anterior hippocampus. One rater measured five brain regions (temporal lobe,
      anterior and posterior hippocampus, amygdala, and temporal horn) on the left and
      right sides of the two non-reformatted and two reformatted scans to obtain inter
      scan variance. Furthermore, most scans were remeasured, to obtain 'reread'
      variances. All data were log-transformed in order to produce comparable
      variability across brain regions of different sizes. For all the regions, except
      the temporal horn, the non-reformatted scans showed significantly larger scan
      rescan variability than the reformatted scans. A typical standard deviation for a
      non-reformatted pair of scans was 0.10, corresponding to 26% error, while a
      typical value for a reformatted pair of scans was 0.04, corresponding to 10%
      error. For all the regions, the reread data (intra-rater reliability) gave
      similar results for both reformatted and non-reformatted images with similar
      standard deviations (typical value for reread standard deviation was 0.020,
      corresponding to 5% error). The data suggest that, even when very thin slices are
      acquired, volume measurement accuracy of gray matter structures in the temporal
      lobe is considerably improved by controlling for image orientation in three
      planes. For these structures, the sample size needed to detect a small (5%)
      within-subject volume change would be halved if reformatted images were used.
      Image contrast is an additional important factor since the reformatted T1
      weighted images used in this study, which have suboptimal CSF/brain contrast,
      worsened measurement accuracy in the temporal horn.

PMID- 9645548
TI  - GABA and brain abnormalities in schizophrenia.
AB  - Some recent autopsy studies indicate that gamma-aminobutyric acid (GABA) function
      is decreased in brain areas that involve some of the well-described structural
      changes observed in schizophrenia. The current study examined the relationship
      between CSF and plasma GABA levels and brain structural measures in
      schizophrenia. Sixty-two drug-free, physically healthy male patients with
      schizophrenia (DSM-IIIR) were evaluated for plasma and CSF GABA, as well as brain
      structural measures on CT scans. Plasma levels of GABA were associated with
      prefrontal sulcal widening and VBRs, but not global sulcal widening in the
      schizophrenic patients. CSF GABA measures were not associated with brain
      structural measures, but were associated with age and age of onset. The
      significant relationship between plasma GABA, but not CSF GABA, and specific
      brain morphology measures in schizophrenic patients suggests that if GABA
      transmission is impaired in schizophrenia, it is a local, but not global,
      phenomenon.

PMID- 9645549
TI  - Evaluation of gender difference in regional brain metabolic responses to
      lorazepam.
AB  - Women are prescribed benzodiazepines twice as frequently as men and there is
      evidence of differences in therapeutic responsiveness to benzodiazepines between
      genders. In this study we compared the regional brain metabolic response to
      benzodiazepines between male and female subjects. Sixteen healthy men and 12
      healthy women were scanned with positron emission tomography (PET) and [F-18]
      fluorodeoxyglucose (FDG) twice: prior to placebo and prior to lorazepam (30
      microg/kg) on separate days. Lorazepam significantly and consistently decreased
      whole brain metabolism and the magnitude as well as the regional pattern of the
      changes was comparable for both genders (M = -4.7+/- 3 and F = -3.9 +/- 3.8
      micromol/100 g/min). Lorazepam effects were largest in thalamus (- 12.5 +/- 6.2
      and -8.6 +/- 7.1 micromol/100 g/min) and occipital cortex (-10.5 +/- 5.5 and 
      10.1 +/- 6.6 micromol/100 g/min). Lorazepam-induced changes in 'relative'
      metabolism were also similar for both genders except for trend differences (0.01
      < P < 0.05) in rectal gyrus, where lorazepam increased relative metabolism in
      women (+4.4 +/- 9.9%) whereas it decreased in men (-3.2 +/- 8.8%, P < 0.04) and
      in cerebellum, where lorazepam-induced decrements were larger in women (-5.9 +/-
      6%) than in men (-1.1% +/- 6.6%, P < 0.05). There were no differences between
      genders for any of the behavioral effects of lorazepam. In summary, this study
      does not show differences in the response to lorazepam between the genders as
      assessed by its behavioral effects and the changes in absolute metabolism; the
      trend toward a difference in the relative changes in rectal gyrus and cerebellum
      merits further investigation.

PMID- 9645550
TI  - SPECT brain blood flow changes with continuous ligand infusion during previously
      learned WCST performance.
AB  - Performance of the Wisconsin Card Sorting Test (WCST) and related brain
      activation patterns reflect both task learning and execution. Normal subjects
      learned the WCST prior to performance during slow SPECT ligand infusion. Blood
      flow increased in bilateral inferior frontal, right middle and inferior parietal
      cortices. Activity decreased in hippocampi, temporal cortex, anterior cingulate
      and caudate.

PMID- 9645551
TI  - SPECT imaging of odor identification in schizophrenia.
AB  - Deficits in olfactory identification, despite normal odor perception, are found
      in some neuropsychiatric disorders, including schizophrenia. We examined if
      regional cerebral blood flow (rCBF) differed between schizophrenia patients and
      controls during odor identification, hypothesizing that these brain regions could
      be relevant to odor identification impairments. Eight schizophrenia and eight
      comparison subjects provided a baseline (picture identity matching) and
      activation (odor identification) SPECT scan, obtained using 99mTc-HMPAO in a low
      dose/high dose design. Six patients and seven controls had analyzable data. MEDX
      data saved in ANALYZE format for SPM 95 generated paired t-test statistical data
      for display in Talairach space, with rCBF changes given as Z-scores. There was no
      schizophrenia vs. control group difference in rCBF for the baseline picture
      matching test. For odor identification, schizophrenia patients had a
      hypometabolic right-sided cortical region that included the frontal lobe Broca's
      area, superior temporal lobe, and supramarginal and angular gyri. Post hoc within
      group contrasts of picture-matching vs. odor identification showed that the
      controls significantly increased rCBF in the right-sided inferior temporal
      fusiform gyrus, and bilateral hippocampi and visual association areas for the
      odor test. The schizophrenia group showed no rCBF differences for picture
      matching compared to odor identification. Patients showed significant
      hypometabolism in right-sided cortical areas for odor identification. They also
      failed to show increased rCBF in the hippocampus and visual association area, as
      seen in controls for odor identification compared to picture-matching. These
      regions may be unique to schizophrenia or have broader implications for olfactory
      memory retrieval.

PMID- 9645552
TI  - Development of glass-ionomer cement systems.
AB  - In the 1960s the idea of positive physico-chemical adhesion with tooth substance
      resulted in the invention of polyacrylic acid-based cements, first the zinc
      polycarboxylate and, subsequently, the glass-ionomer cements. These materials
      were shown to undergo specific adhesion with hydroxyapatite and proved to have
      properties satisfactory for a variety of clinical applications. The key
      properties of the glass-ionomer cements--fluoride release over a prolonged period
      and specific adhesion to enamel and dentine coupled with aesthetic qualities are
      related to their characteristics as aqueous polyelectrolyte systems. In order to
      improve toughness, speed of setting and resistance to dehydration, hybrid
      materials in which some of the water content of the glass-ionomer system was
      replaced by water-soluble polymers or monomer systems capable of ambient
      polymerization were formulated in the late 1980s. These materials, which have
      been termed resin-modified glass-ionomer cements, involve, ideally, the formation
      of an interpenetrating polymer network combining the acid-base cross-linking
      reaction of the metal ion-polyacid with the cross-linking polymerization of the
      monomer system or additive action of the polymers. In the predominantly resin
      materials there is little polyelectrolyte character and it is controversial
      whether such materials should be categorized as glass-ionomer cement systems. The
      specific advantages of these materials over traditional glass-ionomer systems and
      over composite restorative systems remain to be fully documented. Studies of
      adsorption to hydroxyapatite of typical monomers using X-ray photoelectron
      spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (TOF SIMS)
      indicate that resistance to water displacement decreases as hydrophobicity
      increases.

PMID- 9645553
TI  - New trends in glass-ionomer chemistry.
AB  - This paper surveys the different routes to develop glass-ionomer cements (GICs)
      (glass polyalkenoate cements). Using a new commercially available material, Ketac
      Molar, the particular ways of improving conventional GICs are described (mainly
      optimizing the concentration and molecular weight of the polyacid as well as the
      particle size distribution of the glass). High cross-linkage in the GIC matrix is
      the key issue to achieve superior physical properties (three- body wear
      resistance, compressive and flexural strength, surface hardness and solubility).
      This is proven by differential scanning calorimetry and infrared spectroscopy.

PMID- 9645554
TI  - Chemistry of glass-ionomer cements: a review.
AB  - Studies of the setting of glass-ionomer cements have been carried out for over
      twenty years, and there is now a considerable body of information concerning the
      steps that lead to the conversion of a freshly mixed cement paste into a solid,
      durable dental restorative. This paper reviews these studies, paying particular
      attention to more recent work. The conclusion is that glass-ionomers consist of
      interpenetrating networks of inorganic and organic components forming a matrix in
      which particles of unreacted glass are embedded. However, there remain
      uncertainties over aspects of the setting chemistry, for example over the role of
      (+)-tartaric acid in the setting reaction, and over the nature of the fluoride
      species which form during the reaction. The chemistry of resin-modified glass
      ionomers is also discussed and shown to be more complex than that of the simple
      cements. The presence of the resin component slows down the ionic cure reaction
      of the conventional cement, and leads to both a significant exotherm and a set
      material capable of absorbing water reversibly. The paper concludes that the
      microstructure of the set cement depends completely on chemical composition and
      the kinetics of the setting process, and that an understanding of the setting
      chemistry of these materials is thus important for optimal clinical use.

PMID- 9645555
TI  - Influence of alkali metal ions on the fracture properties of glass polyalkenoate
      (ionomer) cements.
AB  - The influence of substituting sodium for calcium on the properties of glass
      polyalkenoate cements was investigated. Two series of glass compositions based on
      PSiO2 x QAl2O3 x 0.75P2O5 x (1 - Z)CaO x XCaF2ZNa2O were studied. The fluorine
      content was fixed at X = 0.50 and 0.75 and the sodium content varied by altering
      Z. The glass polyalkenoate cements formed from these glasses were characterized
      using a linear elastic fracture mechanics (LEFM) approach. In addition,
      compressive strengths of the cements were determined. The properties of the
      cements based on the high fluorine content glasses (X = 0.75) were relatively
      insensitive to sodium content. The Young's modulus, un-notched fracture strength
      and fracture toughness of the cements produced with the lower fluorine content
      glasses (X = 0.5) reduced with sodium content, which was consistent with sodium
      acting to disrupt ionic cross-linking in the polyacrylate matrix. The compressive
      strength was not as dependent on sodium content as the LEFM parameters.

PMID- 9645556
TI  - Fluoride release and uptake by glass-ionomers and related materials and its
      clinical effect.
AB  - The anticariogenic effect of silicate cement is well known and considered a
      result of fluoride release. In several studies a similar fluoride release from
      conventional glass-ionomer cement (GIC) has been established. Therefore, an
      anticariogenic effect may be predicted from the GICs too. In my studies the
      fluoride release was studied by exposing the test specimens to a continuous flow
      of running tap water. At certain time periods the specimens were transferred for
      1 week in a small amount of deionized water (5 ml). The determination of the
      fluoride content of the solution showed the fluoride release of the material at
      that time. There was an initial 'burst' effect of fluoride release and then the
      release gradually decreased, settling at a constant level. The long-term release
      from conventional GICs was shown to remain on the same level for at least 8
      years. The amount of the constant release did not differ much between different
      brands. Resin-modified GICs released fluoride to the same extent and in the
      similar way as conventional GICs whereas polyacid-modified composites
      ('compomers') did not show an initial fluoride 'burst' effect. To study the
      fluoride binding ability of GICs, specimens which had been exposed to running
      water for different periods of time were treated with a 50 ppm fluoride solution.
      After this 'recharging' GIC and resin-modified GIC specimens released more than
      twice the amount of fluoride released before the treatment. The fluoride
      treatment had no effect on polyacid-modified composites or on fluoride-containing
      composites or on the amalgams. To get an impression of the clinical effect of
      GICs a questionnaire was handed out to practitioners attending courses in the
      Nordic countries and in Australia during the period 1991-1992 which resulted in
      954 answers. Among other questions, the dentists were asked if they had observed
      caries and gingival inflammation in association with GIC and composite fillings.
      According to the opinion of most dentists caries and gingival inflammation had
      never or only seldom been observed in association with GIC fillings whereas most
      dentists had observed these complications often in connection with composite
      restorations.

PMID- 9645557
TI  - Fluoride release process of (resin-modified) glass-ionomer cements versus
      (polyacid-modified) composite resins.
AB  - The fluoride release of conventional and resin-modified glass-ionomers is
      reviewed and compared to that of fluoride-releasing (polyacid-modified) composite
      resins. Each formulation displays a typical fluoride release profile. The
      cumulative amount of fluoride released is described by [F]c = [F](I)t/(t + t1/2)
      + beta square root t for glass ionomers whether resin-modified or not, whereas
      for composite resins this quantity is given by [F]c = [F](I)t/(t + t1/2) + alpha
      t. Both equations indicate that two kinetic processes are responsible for the
      fluoride release profiles. The kinetic parameters [F](I), t1/2, beta and alpha
      depend on the formulation. On the basis of the exchange characteristics for
      fluoride, an attempt is made to explain the mechanisms responsible for these
      fluoride release processes.

PMID- 9645558
TI  - Resin-modified glass-ionomers.
AB  - This paper reviews the current status of resin-modified glass-ionomers and
      presents the results of recent findings of research in some key areas. The debate
      on nomenclature pertaining to these products is perceived as being pointless and
      the need for application-based ISO standards is raised. Setting characteristics
      are similar in many respects to those of light-activated composites, although
      some products have limited working time due to the influence of the acid-base
      setting reaction and sensitivity to ambient light. Water absorption and swelling
      are generally very high. The clinical significance of swelling after water
      exposure is unknown. Mechanical properties of most materials lie between those of
      the composites and conventional glass-ionomers depending upon the resin content
      of the matrix phase of the set material. Some products demonstrate an inherent
      adhesion to enamel, although etching may be required in order to make the bond
      clinically effective. Bonding to dentine is probably through a more complex
      mechanism than that involved with conventional glass-ionomers. Conditioning and
      priming of dentine is often advocated. Fluoride release rates and their clinical
      significance is an area which requires clarification and standardization. The key
      factor appears to be the frequency with which the storage water is changed.
      Equilibration is reached within minutes for some materials and their true
      fluoride-releasing potential can only be judged under dynamic test conditions.

PMID- 9645559
TI  - Compomers: between glass-ionomer cements and composites.
AB  - The term 'compomer' was crafted by the producers of the first commercial material
      of this kind: a polyacid-modified composite resin, sold as a filling material for
      some specific applications. This term should recall the composite resins and
      glass-ionomer cements, since some features of these two generic materials are
      found in the compomers. Compomers contain a bifunctional monomer, which should be
      able to react with the pendant methacrylate groups of other monomers, as well as
      with the cations liberated by the glass particles. Several products of this kind
      are now available, and the purpose of this paper is to describe some of their
      specificities and to compare their influence on the mechanical properties, water
      uptake and fluoride release.

PMID- 9645560
TI  - Immediate versus one-month wet storage fatigue of restorative materials.
AB  - Immediate finishing is a highly desirable property of restorative materials. In
      general, the resin composites, the polyacid-modified resin composites and resin
      modified glass-ionomers are finished immediately after light-curing. For the
      conventional glass-ionomers a waiting period of 24 h is recommended. Therefore,
      the objective of this study was to investigate whether immediate finishing and
      application of cyclic loading under water spray on resin-modified glass-ionomers,
      a conventional glass-ionomer, a polyacid-modified resin composite and a resin
      composite are reflected in their Young's modulus and fatigue resistance after 1
      month wet storage compared with a control group that could mature untroubled for
      1 month. From this study, it could be concluded that there is a material
      dependent response on immediate finishing. For the conventional glass-ionomer,
      the waiting period of 24 h is highly advisable. The resin composite suffered more
      than the other test materials. A second statement is that one must be cautious by
      the extrapolation of findings obtained on quasi static tests (Young's modulus)
      towards dynamic properties (flexural fatigue limit).

PMID- 9645561
TI  - Water sorption in resin-modified glass-ionomer cements: an in vitro comparison
      with other materials.
AB  - The pattern of water uptake into a polyacid-modified composite resin (compomer),
      Dyract (D), was assessed using gravimetric analysis and tritiated water
      absorption. The results were compared with a resin composite, Herculite (H), a
      resin-modified glass-ionomer, Fuji II LC (FL), and a conventional glass-ionomer,
      Fuji II (F). Samples were stored in tritiated water for periods varying between 6
      h and 6 months. The resulting change in gravimetric weight and dimensions was
      recorded. The tritiated water content was then assessed using liquid
      scintillation counting and this was compared to the gravimetric changes. The
      inherent water content of each material was also established. D and H showed a
      slow steady net uptake to 3% and 1.3% weight by volume (WV) respectively at 6
      months. FL showed a rapid uptake reaching 8.9% WV at 7 days and 9.3% WV at 6
      months. F showed a steady, less dramatic water uptake reaching 5.3% WV by 6
      months. For the glass-ionomer materials, values for gravimetric water uptake and
      tritium release differed due to the ongoing acid base reaction and an increase in
      firmly bound water. This phenomenon was noted in D suggesting evidence of a
      similar reaction in this material.

PMID- 9645562
TI  - Analysis of reactions in glass-polyalkenoate/resin systems by dielectric
      impedance spectroscopy.
AB  - The principles of impedance spectroscopy are surveyed, with consideration of both
      low and high impedance dielectric biomaterials where the response mechanisms are
      dominated, respectively, by dipolar relaxation and ionic charge migration. The
      situation of dental biomaterials is considered with special reference to glass
      ionomer polyelectrolyte systems and to the impedance changes that may arise in
      consequence of setting mechanisms. Measurements have been conducted using both
      static and frequency-dependent potentials; where appropriate, with a high
      impedance interface and frequency-response analyser. Data are presented for the
      control situation of poly(methyl methacrylate) (PMMA) and for a series of glass
      ionomer and resin-modified glass-ionomer biomaterials. It is observed that in the
      glass-polyalkenoate (G-PA) materials, ionic conduction and polarization are the
      dominant factors contributing to the impedance. This contrasts with the dipolar
      relaxation characteristic of PMMA. It is concluded that a more extended programme
      of data-acquisition is required, where possible from a 'homologous' series of
      formulations, to lay a firm foundation of mechanistic interpretation.

PMID- 9645563
TI  - Biocompatibility of various light-curing and one conventional glass-ionomer
      cement.
AB  - The purpose of this study was to determine and to compare the cellular
      compatibility of modern light-curing (lc) glass-ionomer cements (GICs) to one
      conventional (co) GIC. The following materials were investigated: Ionoseal (IS,
      lc) (VOCO, Germany), Vitrebond (VB, lc) (3M, USA), Compoglass (CG, lc) (Vivadent,
      FL) and Ketac Fil Applicap (KF, co) (ESPE, Germany). From all GICs, equally sized
      specimens (height 2 mm, diameter 5 mm) were polymerized or set according to the
      instructions of the manufacturers. Various extracts of all specimens were
      obtained by subsequent elutions. Human primary fibroblasts of the attached
      gingiva (HGF) and permanent mouse fibroblasts (3T3) were used for the
      experiments. HGF and 3T3 cells were exposed to the extracts of all materials for
      48 h. Growth inhibition due to cytotoxic effects was determined by staining the
      cultures with Hoechst 33342 (determination of DNA and cell vitality). It was
      found that the material CG induced no growth inhibition in any of the assays.
      Proliferation of HGF was not, or only slightly, inhibited by the extracts of the
      materials IS and KF, whereas severe alterations were caused by the extracts of
      the material VB. Growth of 3T3 cells was only moderately or slightly reduced by
      the extracts of materials IS and KF respectively, but was severely or totally
      inhibited by all extracts of VB. From our results we conclude that the GIC VB is
      very cytotoxic and therefore may also induce alterations in vivo. All other
      investigated GICs revealed excellent (CG), or good (IS, KF) cellular
      compatibility.

PMID- 9645564
TI  - Glass-ionomers: bioactive implant materials.
AB  - Glass-ionomer cements (GICs) originally designed for use as dental materials have
      a number of advantages over acrylic bone cements. These include lack of exotherm
      during setting, absence of monomer and improved release of incorporated
      therapeutic agents; this has resulted in the development of GICs for biomedical
      applications. Major landmarks in this history are the formulation of defined
      composition ionomer glasses and an improved understanding of the biological and
      material properties of GICs. Following implantation, GICs can form a stable
      integration with bone, and affect the growth and development of bone, both
      adjacent to their surface and systemically, through an ion release mechanism. The
      'non-inert' nature of this group of materials is also demonstrated by their
      adverse effects on neural tissue. Successful clinical use of GICs, both as bone
      cements and as preformed implants for hard tissue replacement, have been reported
      in the fields of otologic surgery (Cochlear implant fixation, repair of the
      tympanic chain, eustation tube obliteration and as ear ossicles), and oral and
      reconstructive surgery. The use of GICs in situations where they will come into
      contact with nerves or neural tissue is contraindicated.

PMID- 9645565
TI  - Clinical performance of glass-ionomers.
AB  - Glass-ionomers were introduced to the profession 20 years ago and have been shown
      to be a very useful adjunct to restorative dentistry. Their major advantages
      include the ion exchange adhesion to both enamel and dentine and a continuing
      fluoride release throughout the life of the restoration. The chemistry of the
      setting reaction is essentially an acid/base reaction but recent research has
      introduced variations in an effort to improve clinical handling. Small additions
      of resin increase the physical properties to a degree and allow for a light
      initiated setting mechanism. However, it is essential that the acid/base reaction
      remains dominant if the full advantages of the glass-ionomer are to be retained.
      The material has multiple uses in dentistry and it shows a high degree of
      biocompatibility to the pulp and surrounding soft tissues. The main limitation at
      this time is a relatively low fracture resistance but it is possible to protect
      it through lamination with stronger materials if the need arises. This paper
      examines the essential parameters for successful clinical placement and comments
      on its longevity.

PMID- 9645566
TI  - Confocal microscopic observation of structural changes in glass-ionomer cements
      and tooth interfaces.
AB  - This study aimed to develop techniques to allow dynamic imaging of a cavity
      before, during and after placement of glass-ionomer restorative materials.
      Cavities were cut in recently extracted third molars and the teeth longitudinally
      sectioned. Each hemisected tooth surface was placed in green modelling compound
      at 90 to the optical axis of the microscope. The cavity surface was imaged using
      a video rate confocal microscope in conjunction with an internally focusable
      microscope objective. The sample on the stage was pushed up to the objective lens
      which 'clamped' the cover glass onto it. Water, glycerine or oil was placed below
      the coverglass, with oil above. Internal tooth structures were imaged by changing
      the internal focus of the objective. The restorative material was then placed
      into the cavity. Video images were stored either onto video tape or digitally,
      using a frame grabber, computer and mass memory storage. Software controls
      produced time-lapse recordings of the interface over time. Preliminary
      experiments have examined the placement and early maturation of conventional
      glass-ionomer cements and a syringeable resin-modified glass-ionomer cement.
      Initial contact of the cement matrix and glass particles was visible as the
      plastic material rolled past the enamel and dentine, before making a bond.
      Evidence for water movement from the dentine into the cement has also been seen.
      After curing, the early dimensional changes in the cements due to water flux were
      apparent using the time-lapse facility. This new technique enables examination of
      developing tooth/restoration interfaces and the tracking of movement in
      materials.

PMID- 9645567
TI  - Bonding orthodontic brackets with glass-ionomer cement.
AB  - This is a clinical paper outlining the experience of an enthusiastic group of
      seven individuals in different local orthodontic practices who, over a period of
      six years, have bonded some 99% of the metal orthodontic brackets to tooth enamel
      using glass ionomer cement (GIC). Up until recently GIC has been little used
      within the orthodontic world for the cementing of orthodontic brackets, composite
      resin being the conventional adhesive. We use GIC as a bracket adhesive because
      there is a very low incidence of tooth enamel decalcification occurring around
      the brackets with its use compared with the more universally used composite resin
      adhesives. This paper details the perceived clinical advantages and
      disadvantages, and then defines the three critical areas for successful bonding
      with GIC, followed by a description of the chairside technique.

PMID- 9645568
TI  - Busulfan, cyclophosphamide and total body irradiation as conditioning for
      allogeneic bone marrow transplantation for acute and chronic myeloid leukemia.
AB  - Fifty patients with acute myeloid leukemia (AML) or chronic myeloid leukemia
      (CML) underwent allogeneic bone marrow transplantation between October 1988 and
      January 1997. Patients received 8 mg/kg of busulfan (BU) with 120 mg/kg of
      cyclophosphamide (CY) followed by 10 Gy of total body irradiation (TBI). Twenty
      consecutive patients with AML in first remission (n = 9) or CML, in chronic phase
      (n = 11) entered the study (group I). Thirty consecutive patients with advanced
      myeloid malignancies including AML (n = 19) and CML (n = 11) also entered the
      study (group II). The probability of leukemia-free survival at 5 years was 85%
      for group I patients and 50% for group II patients. Severe regimen-related
      toxicities occurred in 16% of patients (two in group I, six in group II). The
      most common sites affected by severe toxicities were lung (n = 6), liver (n = 2)
      and heart (n = 2). The relapse rate was higher for patients allografted in
      advanced stages of disease (O% at 5 years for group I and 28% for group II).
      These results suggest that BU + CY + TBI is a very effective conditioning regimen
      in patients with myeloid malignancies.

PMID- 9645569
TI  - Big BU/CY is associated with a favorable long-term outcome in patients
      allotransplanted for chronic myelogenous leukemia in chronic phase.
AB  - Twenty-six adult patients, median age 36 years (range 21-53) with chronic myeloid
      leukemia in first chronic phase were allotransplanted between October 1989 and
      May 1995. The preparative regimen consisted of busulphan 16 mg/kg and
      cyclophosphamide 200 mg/kg (big BU/CY). Cyclosporin A and methotrexate were used
      for GVHD prophylaxis. Twenty-two donors were HLA-identical siblings and four
      donors were mismatched for one antigen of class I. The global incidence of acute
      GVHD was 50%, that of severe aGVHD (grades 3-4) was 11%; the global incidence of
      chronic GVHD was 30%. No patients developed veno-occlusive disease of the liver
      or interstitial pneumonia. Five patients died, one of relapse, four of transplant
      related causes, mostly related to aGVHD; thus, the transplant-related mortality
      was 16%. Twenty-one patients are alive, in remission, with a median follow-up of
      55 months (range 24-90); actuarial probability of survival is 78% (CI 64-96). Our
      study shows that this conditioning regimen is relatively easy to administer and
      seems to be as effective as, if not superior to, regimens containing TBI, in
      patients with chronic myeloid leukemia in chronic phase and the transplant
      related mortality is not excessive even in older patients.

PMID- 9645570
TI  - G-CSF serum pharmacokinetics during peripheral blood progenitor cell
      mobilization: neutrophil count-adjusted dosage might potentially improve
      mobilization and be more cost-effective.
AB  - The optimal dosing schedule of G-CSF for peripheral blood progenitor cell (PBPC)
      mobilization is still under investigation although many centers use 10
      microg/kg/day in a single subcutaneous dose. However, G-CSF clearance increases
      with increasing absolute neutrophil count (ANC). Hence a G-CSF dosage adjusted to
      ANC might be a reasonable approach. We measured G-CSF trough serum levels by
      sandwich ELISA assay at different ANCs in eight patients undergoing treatment
      with filgrastim at 10 microg/kg/day in a single subcutaneous dose. A total of 26
      samples were analyzed, and a strong correlation between increasing ANC and
      decreasing G-CSF levels was found by linear regression analysis (P < 0.0003, r2 =
      0.4199). For ANC values above 5000/microl the trough serum levels, ie 24 h after
      administration, were consistently below the level that provides maximal
      clonogenic precursor stimulation in vitro (10 ng/ml). Serial serum G-CSF
      measurements performed in three patients at 0, 3, 6, 9 and 24 h after G-CSF
      administration, showed a reduction of the area under the curve (AUC) with
      increasing ANC. For an ANC of 20000/microl or greater, the G-CSF serum level fell
      under the maximal in vitro stimulation threshold of 10 ng/ml within 12 h. This
      preliminary pharmacokinetic data seems to suggest that an ANC-adjusted G-CSF
      dosing schedule might improve the design of PBPC mobilization regimens.

PMID- 9645571
TI  - Detection of maternal DNA in umbilical cord blood by polymerase chain reaction
      amplification of minisatellite sequences.
AB  - One of the concerns about the use of cord blood as a source of hematopoietic stem
      cells for allogeneic transplantation is the possibility of contamination by
      maternal cells which could cause life-threatening GVHD. We have assessed cord
      blood contamination using PCR analysis of several minisatellite regions to detect
      maternal DNA. Eighty mother-cord pairs were obtained for this study. In one case
      there were no specific maternal alleles at any loci and, therefore, cord blood
      could not be evaluated. Thus, there was a total of 79 informative cases for the
      detection of maternal cells in the fetal circulation. In most cases, the level of
      detection was between 0.5 and 1%. We detected maternal DNA in the cord blood
      sample in only one case (1.26%), and the analysis of dilution experiments led to
      an estimate of 0.5-1% maternal cells. In conclusion, using PCR amplification of
      hypervariable regions, maternal DNA is very rarely detected in the cord blood
      collected at birth, although this approach has a relatively low level of
      sensitivity.

PMID- 9645572
TI  - Long-term follow-up after high-dose therapy for high-risk multiple myeloma.
AB  - Between 1985 and 1990, 133 patients with advanced multiple myeloma (MM) (74%
      resistance; 41% resistant relapse, RR) were treated with five high-dose therapy
      (HDT) regimens including: melphalan < or =100 mg/m2 (MEL 100) (46 patients); MEL
      100 plus GM-CSF (24 patients); MEL 140 plus autologous bone marrow
      transplantation (ABMT) (eight patients); MEL 140 plus TBI 850 cGy plus ABMT (37
      patients); and thiotepa 750 mg/m2 (THIO 750) + TBI 850 cGy plus ABMT (18
      patients). The median follow-up of alive patients as of December 1997 was 9
      years. Overall, 17% experienced treatment-related mortality within 60 days (TRM)
      and 12% achieved stringently defined complete remission (CR) with a median
      duration of 16 months; four of 16 patients (25%) remain in CR at 10 years. The
      median durations of event-free survival (EFS)/overall survival (OS) were 6/15
      months. Superior EFS/OS were noted with MEL 100 plus GM-CSF and the two TBI
      containing regimens (9/24 months among 79 patients) compared to the remaining 54
      patients receiving MEL < or =100 or MEL 140 plus ABMT (3/5 months) (P =
      0.0001/0.0001, respectively). Multivariate regression analyses (MVA) were
      performed so that, despite patient heterogeneity among the five treatment groups,
      potentially relevant disease, host, treatment, and supportive care variables
      could be identified that were associated with TRM, CR, EFS and OS. TRM was higher
      with creatinine >2.0 mg/dl, absence of ABMT/GM-CSF support and age >50 years; CR
      was superior with TBI-containing regimens and < or =12 months of prior therapy;
      EFS and OS both were longer with B2M < or =2.5 mg/l, age < or =50 years, absence
      of RR and with ABMT/GM-CSF support. In the presence of >2 favorable variables (32
      % of patients), median EFS/OS durations of 18/48 months were observed which
      progressively declined with 2 and <2 favorable parameters to 6/11 months (28% of
      patients) to 3/5 months (40% of patients) (P = 0.0001/0.0001). At 10 years, 10
      and 20% of patients with >2 favorable variables were event-free and alive, which
      was also true for the 37 patients receiving MEL 140 plus TBI. To appreciate
      possible long-term contributions of supportive care or treatment intensity,
      landmark analyses performed at 1, 2, 4 and 6 months revealed virtually identical
      ranking orders of prognostically favorable variables to those seen pre-HDT; once
      supportive care was accounted for, regimen intensity with added TBI did not
      emerge as an independent favorable feature.

PMID- 9645573
TI  - First and second apheresis in patients with multiple myeloma: no differences in
      tumor load and hematopoietic stem cell yield.
AB  - Autologous peripheral blood stem cells (PBSC) are now widely used to support
      myeloablative therapy in patients with multiple myeloma (MM). The presence of
      malignant cells in these autografts has been demonstrated. Characteristic
      kinetics with differential and concomitant mobilization of CD34+ and malignant
      cells after high-dose (HD) chemotherapy and hematopoietic growth factor
      administration have been reported. We determined the amounts of tumor cells and
      PBSC in leukapheresis products (LP) collected on day 1 (LP1) and 2 (LP2) from 16
      MM patients harvested after HD chemotherapy and G-CSF. Furthermore, LP from six
      patients collected on day 5 (LP5) could be examined. The content of clonotypic
      cells was quantitated by an allele-specific oligonucleotide (ASO)-PCR assay based
      on limiting dilutions. CD34+ PBSC were determined by flow cytometry. The
      percentages of malignant cells in the leukapheresis products were in the range of
      0% to 0.713% (mean 0.047%). CD34+ cells ranged between 0.06% and 5.4% (mean
      1.23%). Comparing LP1 with LP2, no differences in the quantity of tumor cells
      (mean 0.0538% vs 0.0448%; P = 0.96) and CD34+ cells (mean 1.49% vs 1.33%; P=
      0.50) were seen. The calculated number of tumor cells per CD34+ cell did not
      differ significantly (mean 0.0420 vs 0.0249; P = 0.65). Analyzing LP5 revealed no
      changes in the number of tumor cells per CD34+ cell (0.0511 vs 0.1044; P = 0.46)
      indicating a relatively constant ratio of PBSC to tumor cells during the course
      of PBSC harvesting. These results offer the possibility of combining LP harvested
      over several days without increasing the tumor load per CD34+ cell.

PMID- 9645574
TI  - High-dose chemotherapy in patients with breast cancer: evaluation of infusing
      peripheral blood stem cells containing occult tumor cells.
AB  - The purpose of this study was to evaluate the frequency of detecting occult tumor
      cells in peripheral blood stem cell (PBSC) harvests and to determine the impact
      of infusing such cells on relapses after high-dose chemotherapy (HDC). Peripheral
      blood stem cell harvests from 223 patients with breast cancer were examined by an
      immunocytochemistry (ICC) method for detection of occult tumor cells, and infused
      after HDC without consideration of test results. Two hundred and four patients,
      114 with stage II-III and 90 with stage IV disease who received only PBSC, that
      were tested by ICC were evaluated for time to relapse. Five hundred and eighty
      one of 619 PBSC harvests (94%) from 223 patients were tested. Fifty-three of 581
      harvests (9%), 8% from stage II-III and 10% from stage IV patients, were positive
      by ICC (P = 0.68). Forty-one of 223 patients (18%), 17/122 (14%) with stage II
      III and 24/101 (24%) with stage IV disease, had positive harvests (P = 0.06).
      Eleven percent of patients who had 1-2 harvests tested were positive as compared
      to 32% of patients who had > or =3 PBSC harvests tested (P < 0.001). Nineteen
      patients who were infused with a mixture of ICC negative and untested PBSC
      harvests were excluded from analyses of relapse. The probabilities of relapse at
      18 months for the 97 patients with stage II-III disease infused with ICC-negative
      and the 17 with ICC-positive PBSC were 0.19 and 0.13, respectively (P = 0.48).
      The probabilities of relapse at 18 months for patients achieving a CR or a CR in
      non-bone sites and improvement in bone lesions were 0.55 for the ICC-negative
      group (n = 30) and 0.45 for the ICC-positive group (n = 11) (P = 0.60). It was
      concluded that occult tumor cells were detected by ICC in PBSC harvests from a
      relatively small fraction of women with breast cancer, but were not associated
      with a significant increase in the probability of early relapse or progression
      when infused after HDC.

PMID- 9645575
TI  - Association of pulmonary function testing abnormalities and severe veno-occlusive
      disease of the liver after marrow transplantation.
AB  - We investigated an association between pulmonary function testing (PFT) before
      bone marrow transplantation and the development of severe veno-occlusive disease
      (VOD) of the liver. We previously noted that reductions in diffusing capacity of
      the lung for carbon monoxide (corrected for hemoglobin) (D(L)COc) were associated
      with mortality after transplantation, but this was not caused by respiratory
      failure. We performed a case-series review of prospectively collected data from
      307 marrow recipients who underwent PFT within 2 weeks of transplantation. Of
      these, 170 (56%) developed VOD; 39 (13%) mild, 81 (26%) moderate, and 50 (16%)
      severe or fatal. Both total lung capacity (TLC) and D(L)COc were associated with
      severe VOD in univariate analysis (P = 0.006 for each). However, D(L)COc entered
      logistic regression models that contained variables for all known risk factors
      for severe VOD, while TLC did not contribute additional predictive information.
      The odds ratio (OR) associated with a D(L)COc below the lower limits of normal
      (70% of predicted) was 2.4 (95 % CI, 1.0 to 5.4; P = 0.04). We conclude that
      reduced diffusion capacity of the lung measured before marrow transplantation is
      an independent risk for severe hepatic VOD. We speculate that the decreased
      D(l)COc indicates pre-existing systemic endothelial cell damage and a
      susceptibility to severe hepatic injury from chemotherapy.

PMID- 9645576
TI  - Incidence and influence of GB virus C and hepatitis C virus infection in patients
      undergoing bone marrow transplantation.
AB  - Markers of GB virus C (GBV-C) and hepatitis C virus (HCV) were sought in 80
      patients before and after they underwent BMT in a metropolitan hospital in Tokyo
      between 1990 and 1996. RNA of GBV-C was detected in 14 (18%) patients before BMT.
      Of the 55 patients who had been transfused, 14 (25%) possessed GBV-C RNA at a
      frequency significantly higher than in the 25 untransfused patients who were all
      negative (P < 0.01). HCV RNA was detected in three of the 55 (5%) transfused
      patients, but in none of the 25 untransfused patients. Sera at 3 months after BMT
      were available for 57 patients. GBV-C RNA persisted in all 10 patients who were
      infected before BMT, while it was detected in five of the remaining 47 (11%)
      patients who were not. However, persistent and/or ongoing GBV-C infection had no
      appreciable influence on patient morbidity or mortality. Two of the 57 patients
      were positive for HCV RNA before BMT and this persisted after BMT in both. HCV
      RNA became positive in eight of the remaining 55 (15%) patients who were negative
      before BMT. Of the 14 patients who received transfusions screened by the first
      generation test at BMT, seven (50%) became positive for HCV RNA, a rate
      significantly higher than the one of 41 (2%) patients who received transfusions
      screened by the second-generation test (P < 0.001). These results indicate that
      BMT patients are at increased risk of GBV-C infection transmitted by transfusions
      received before and at the time of BMT, and that the risk of HCV infection has
      decreased after the implementation of the second-generation anti-HCV test.

PMID- 9645577
TI  - Unique risk factors for bacteraemia in allogeneic bone marrow transplant
      recipients before and after engraftment.
AB  - A study of the risk factors associated with bacteraemia in 191 allogeneic bone
      marrow transplant (BMT) recipients (1991-1996) was performed. In contrast to risk
      factors commonly cited for cancer chemotherapy, mucositis, degree of conditioning
      toxicity of the gut and lungs, duration of neutropenia, and severity of
      neutropenia and monocytopenia were not associated with bacteraemia in the pre
      engraftment period, during which the only significant risk factor was late stage
      underlying disease (P < 0.05). After engraftment, Hickman catheter infection, and
      severe acute and chronic graft-versus-host disease (GVHD) were found to be
      independently associated with bacteraemia by multivariate analysis (P < 0.001,
      <0.05 and <0.05, respectively). This might be explained by intense antimicrobial
      prophylaxis, early empirical treatment, and non-routine use of haemopoietic
      growth factors. No significant difference in mortality was detected between
      bacteraemic and non-bacteraemic patients in both periods. Allogeneic BMT
      recipients are therefore a group of patients distinct from other cancer patients
      receiving chemotherapy at risk of developing bacteraemia. The study findings
      prompt consideration of a management protocol incorporating early and routine use
      of haemopoietic growth factors before engraftment in high-risk patients with late
      stage underlying malignancies, routine antimicrobial prophylaxis for acute GVHD
      with intense immunosuppression, and intravenous immunoglobulin therapy for
      chronic GVHD. Further cost-benefit analyses are warranted.

PMID- 9645578
TI  - Safety and efficacy of spinal vs general anaesthesia in bone marrow harvesting.
AB  - Bone marrow harvesting (BMH) can be performed with either general (GA) or spinal
      anaesthesia (SPA). Whether SPA is advantageous in BMH and if this technique is
      safe for procedures performed in the prone position is still controversial. To
      evaluate the safety and efficacy of both anaesthetic techniques in BMH, 37
      allogeneic donors (nine female, 28 male; 34.3 +/- 9 years; ASA class 1-2)
      received either spinal (group 1, n =20) or general anaesthesia (group 2, n = 17)
      according to their personal wishes. Under standardised harvesting conditions,
      haematology parameters, cell counts (MNC, CD34+), haemodynamic parameters,
      adverse reactions and patient satisfaction were registered. No differences were
      seen between groups with respect to demographic data, harvesting time (55 +/- 17
      vs 60 +/- 16 min) and bone marrow cell counts (MNC: 6.68 +/- 2.1 vs 5.7 +/- 1.7
      ml/10(6)). The incidence of hypotension was higher in group 1 (45 vs 10.8%; P
      =0.042). Postoperative analgesic requirement and emesis were increased in group 2
      (P < 0.04) in comparison to group 1. In conclusion, the present study failed to
      show superiority of spinal over general anaesthesia with regard to the quality of
      the harvested bone marrow. However, the lower incidence of complaints after
      spinal anaesthesia appears to offer an advantage over GA in healthy allogeneic
      bone marrow donors.

PMID- 9645579
TI  - Routine fluoroscopic guidance is not required for placement of Hickman catheters
      via the supraclavicular route.
AB  - The purpose of this study was to evaluate the efficacy and safety in placement of
      Hickman catheters via the supraclavicular route without fluoroscopic guidance. We
      studied 81 consecutive percutaneous placements of dual lumen Hickman catheters
      via the supraclavicular route without the use of fluoroscopic guidance. Success
      rates, technical problems, complications, infections and reasons for explantation
      were recorded prospectively. Seventy-nine punctures were successful (97.5%). One
      pneumothorax (1.2%) and three accidental arterial punctures (3.7%) occurred.
      Difficulties in introducing the catheter through the peel away sheath or
      misplacement were not observed. The catheters remained in place for a total of
      7657 days (mean 94.5, range 3-392 days). Sixteen blood cultures were positive
      (2.1/1000 catheter days). Five catheters (6.1%) were lost because of mechanical
      complications. Forty-two lines (52%) were removed electively, 23 (28.4%) because
      of suspected infection, and two (2.5%) because of tunnel infection. Nine patients
      died with a functioning catheter. We conclude that the supraclavicular approach
      to the subclavian vein is safe and efficient for introduction of Hickman
      catheters. Using this access, routine fluoroscopic or sonographic guidance is not
      required for proper placement. Implantation of the lines in an intensive care
      unit did not lead to higher infection rates than those reported in the
      literature.

PMID- 9645580
TI  - Pneumoperitoneum without peritonitis after allogeneic peripheral blood stem cell
      transplantation.
AB  - Allogeneic blood stem cell transplantation is associated with multiple
      complications. We report a case of pneumoperitoneum without peritonitis
      associated with colonic pneumatosis in a patient who had undergone an allogeneic
      peripheral blood cell transplant

PMID- 9645581
TI  - Donor lymphocyte transfusion for the treatment of Epstein-Barr virus-associated
      lymphoproliferative disorder of the brain.
AB  - EBV-associated lymphoproliferative disorder (LPD) is a rare but serious
      complication in marrow transplant recipients. A 31-year-old Japanese woman in the
      second chronic phase of CML received an allogeneic BMT from her HLA 2-locus
      incompatible 62-year-old father. Around day +200, she developed EBV-LPD of the
      right parieto-temporal lobe which caused slowly progressive left hemiparesis. Two
      courses of donor lymphocyte transfusions (DLT) of 10(6)CD3+ T cells/kg of body
      weight failed to suppress her central nervous system (CNS) EBV-LPD. The patient
      died of recurrent blastic crisis of CML. This case suggests that DLT may be
      ineffective for the treatment of CNS EBV-LPD.

PMID- 9645582
TI  - Acquired ichthyosis associated with chronic graft-versus-host disease following
      allogeneic peripheral blood stem cell transplantation in a patient with chronic
      myelogenous leukemia.
AB  - Acquired ichthyosis (AI) has rarely been described following bone marrow
      transplantation (BMT). We report a 29-year-old male, who underwent allogeneic
      peripheral blood stem cell transplantation (alloPBSCT) for chronic myelogenous
      leukemia, and who developed AI associated with chronic graft-versus-host disease
      (cGVHD). Both of these disorders were treated successfully with cyclosporin A. We
      conclude that AI may be related to an autoimmune process on the basis of cGVHD,
      and dermathopathologic evaluation must be performed in patients with skin changes
      suggesting AI following allogeneic bone marrow transplantation.

PMID- 9645583
TI  - Graft-versus-myeloma after donor leukocyte infusion: maintenance of marrow
      remission but extramedullary relapse with plasmacytomas.
AB  - Adoptive immunotherapy with donor leukocytes has emerged as a promising strategy
      for the treatment of myeloma recurrence after allogeneic transplantation. 2.9 x
      10(8)/kg donor mononuclear cells containing 1.4% CD34+ and 37% CD3+ cells were
      administered to a 48-year-old patient with non-secretory plasmablastic myeloma
      relapsing 9 months after a blood stem cell transplant from his HLA-identical
      sibling. In view of the extensive marrow infiltration and the aggressive
      behaviour of the disease, the donor cells were preceded by a course of EDAP
      chemotherapy. There was rapid clinical improvement, and CR was achieved on day 30
      post infusion. However, three subcutaneous plasmacytomas showing anaplastic
      features developed within a few days. These failed to respond to interferon-alpha
      and continued to grow for 5 weeks in the absence of marrow plasmacytosis or other
      evidence of systemic disease. Grade 3 acute liver GVHD developed on day 79 which
      was controlled with immunosuppression. Overt systemic relapse occurred on day 90
      as the GVHD came under control. The course of our case suggests highly
      proliferative malignant cells may escape the graft-versus-tumour effect of
      immunocompetent allogeneic cells in extramedullary sites subsequently resulting
      in overt systemic relapse if left untreated. New approaches are needed to deal
      with the problem of extramedullary disease recurrence.

PMID- 9645584
TI  - Flow cytometry comparison of CD34+ subsets in bone marrow and peripheral blood
      after priming with glycosylated or non-glycosylated rhG-CSF.

PMID- 9645585
TI  - Treatment of patients with malignant lymphoma with Mini-BEAM reduces the yield of
      CD34+ peripheral blood stem cells.

PMID- 9645586
TI  - Heat shock proteins in inflammation and asthma: Dr Jekyll or Mr Hyde?

PMID- 9645587
TI  - Epithelial repair in asthma. Do the benefits of house dust mite avoidance result
      from proteinase avoidance?

PMID- 9645588
TI  - What causes airway remodelling in asthma?

PMID- 9645589
TI  - Exposure-response relationships of occupational inhalative allergens.
AB  - Only a few threshold limit values exist at present for allergens in the workplace
      known to cause bronchial asthma. This contrasts with the great number of
      occupational asthma cases observed in industrialized countries. Recently
      published studies provide clear evidence for exposure intensity response
      relationships of occupational allergens of plant, microbiological, animal or man
      made origin. If allergen exposure levels fall short of determined limit values,
      they are not associated with an increased risk of occupational asthma.
      Corresponding data are available for wheat flour (1-2.4 mg/m3), fungal alpha
      amylase (0.25 ng/m3), natural rubber latex (0.6 ng/m3), western red cedar (0.4
      mg/m3) and rat allergens (0.7 microg/m3). It is suggested to stipulate legally
      binding threshold limit values (TLV/TWA) on this basis in order to induce more
      effective primary preventive measures. If no reliable data on the health risk of
      an occupational airborne noxa exist, the lowest reasonably practicable exposure
      level has to be achieved. Appropriate secondary preventive measures have to be
      initiated in all workplaces contaminated with airborne allergens. Verified
      exposure-response relationships provide the basis for risk assessment and for
      targeted interventions to reduce the incidence of occupational asthma also in
      consideration of cost benefit aspects. 'Occupational asthma is a disease
      characterized by variable airflow limitation and/or airway hyperresponsiveness
      due to causes in a working environment. These causes can give rise to asthma
      through immunological or non-immunological mechanisms. Up to 15% of all asthma
      cases are of occupational origin or have at least a significant causal
      occupational factor. According to the New Zealand part of the European
      Respiratory Health Survey, an increased risk of asthma prevalence was found for
      several occupations such as laboratory technicians, food producers, chemical
      workers, plastic and rubber workers. The Spain part of this study comprising 2646
      Spanish subjects showed an asthma risk to be attributed to occupational exposures
      between 5 and 6.7%. Main asthma-inducing agents in the workplace are flour, grain
      and feed dust, animal dander/urinary proteins and isocyanates. Further, several
      inhalative irritants such as chlorine, acid or alkaline aerosols play a pivotal
      role. Many low molecular weight chemicals have irritative as well as allergenic
      effects on the airways, e. g. isocyanates and acid anhydrides. In addition to
      chronic or repetitive exposures, also singular accidental exposure to high
      concentrations of irritative or toxic airborne substances can cause occupational
      asthma. This condition is frequently called reactive airways dysfunction.

PMID- 9645590
TI  - Hypothalamic-pituitary-adrenal function in children with asthma and rhinitis
      treated with topical glucocorticosteroids.
AB  - BACKGROUND: The risk of suppression of hypothalamic-pituitary-adrenal (HPA)
      function in children on topical glucocorticosteroids is currently much debated.
      OBJECTIVE: To review data on HPA function in children with asthma and rhinitis on
      topical glucocorticosteroids, and to discuss the value of HPA function measures
      in clinical practice and research. METHOD: A review of peer refereed data.
      RESULTS/CONCLUSIONS: There is no evidence that insufflated or inhaled
      glucocorticosteroids in recommended doses have ever caused clinically significant
      HPA insufficiency in any child. Using sensitive measures of basal adrenal
      activity, however, several studies have found suppressive effects with specific
      drugs, high doses and application systems. These observations may represent
      homeostatic diminution in endogenous cortisol. Such measures have no place in the
      management of children on topical glucocorticosteroids, but may be useful in
      clinical trials assessing systemic activity of administration regimens and
      application devices. In children growth suppression seems to the most important
      adverse effect of topical glucocorticosteroids.

PMID- 9645591
TI  - Heat shock protein 70 upregulation is related to HLA-DR expression in bronchial
      asthma. Effects of inhaled glucocorticoids.
AB  - BACKGROUND AND OBJECTIVE: Antigen processing determines the production of
      peptides from antigens - including allergens - and their binding to class II
      major histocompatibility complex molecules, that stimulate T-cell responses. Heat
      shock protein (hsp) 70 are recognized to have a role in chaperoning antigenic
      peptides and in facilitating class II peptide assembly. We studied the HLA-DR and
      hsp70 expression on BAL cells and bronchial biopsies from asthmatics, as well as
      the effect of low dose fluticasone propionate treatment. METHODS: Twenty-three
      asthmatics and eight normal subjects were selected. In each subject BAL and
      bronchial biopsies were performed. Eighteen out of 23 asthmatics, underwent the
      second bronchoscopy after 6 weeks of low dose inhaled fluticasone propionate
      treatment (250 microg b.d.) in a placebo-controlled double-blind study. BAL fluid
      and biopsies were processed to evaluate HLA-DR and hsp70 expression by
      immunochemistry methods. RESULTS: Hsp70 and HLA-DR upregulation was present on
      professional and non-professional antigen presenting cells (APCs). In asthmatics,
      the hsp70 and HLA-DR expression was higher in BAL (hsp70 P<0.001, HLA-DR P<0.001)
      and bronchial epithelium (hsp70 P<0.001, HLA-DR P<0.001) when compared with
      controls. We also observed a significant correlation between hsp70 and HLA-DR
      expression in BAL (P<0.005) and epithelium (P<0.001). Fluticasone propionate
      treatment down-regulated the hsp70 and HLA-DR expression in BAL (hsp70 P < 0.001,
      HLA-DR P < 0.05) and bronchial epithelium (hsp70 P < 0.05, HLA-DR P < 0.05). A
      serial section comparison study showed that CD1a+ cells and macrophages were
      positive for both hsp70 and HLA-DR in the submucosa. CONCLUSIONS: Our results
      support the hypothesis that hsp70 over-expression implies a potential role for
      these proteins in antigen processing and/or presentation resulting in an
      increased activity of APCs, which is essential for the initiation and modulation
      of the asthmatic immune response in chronic asthma. Fluticasone propionate
      induces downregulation of HLA-DR and hsp70 molecules thus regulating inflammation
      by affecting key mechanisms of the allergic response.

PMID- 9645592
TI  - Mite-antigen avoidance can reduce bronchial epithelial shedding in allergic
      asthmatic children.
AB  - BACKGROUND: Asthma is characterized by bronchial hyperresponsiveness (BHR),
      bronchial mucosa inflammation and airway epithelial damage. OBJECTIVE: This study
      was designed to evaluate the effect of mite avoidance on bronchial epithelial
      shedding in asthmatic children sensitized to Dermatophagoides. METHODS: The
      percentages of airway epithelial cells and eosinophil have been counted in
      samples obtained by hypertonic saline-induced sputum before and after a period of
      antigen avoidance in an Alpine environment (1756 m). The degree of bronchial
      hyperresponsiveness to methacholine was also evaluated. RESULTS: After avoidance
      the median (lower, Q1, and upper, Q3, quartile) percentage of epithelial cells in
      the sputum decreased significantly from 3.50 [0.50;6.98] to 0 [0;0.5] (P=0.012)
      and eosinophil percentage decreased from 1 [0;5.25] to 0 [0,1.5] (P<0.05). Median
      (Q1,Q3) PC20 increased significantly from 2.75 [1.53;7.5] to 3.25 [1.65;15.25]
      mg/ mL (P=0.038). After 3 weeks of re-exposure to mite the epithelial median
      (Q1,Q3) percentage raised to 3.90 [1.5;6] (P = 0.027), eosinophils to 1.5
      [0;3.00] (NS) and PC20 was 5.25 [1.68;14.50] (NS). CONCLUSION: Exposure to house
      dust mite antigen can induce airway epithelial shedding even in subjects with low
      eosinophil airway infiltration, thus supporting the idea that epithelial damage
      in asthmatics sensitized to Dermatophagoides may be due to a proteolytic activity
      of the mite major antigens.

PMID- 9645593
TI  - Inhaled corticosteroid reduced lamina reticularis of the basement membrane by
      modulation of insulin-like growth factor (IGF)-I expression in bronchial asthma.
AB  - BACKGROUND: Pathological studies of bronchial biopsy specimens have confirmed the
      apparent thickening of lamina reticularis of the epithelial basement membrane.
      Corticosteroids have proven to be most effective in modifying airway
      inflammation. However, there is not much data on the effects of corticosteroid
      treatment on the basement membrane. OBJECTIVE: To investigate the effects of
      inhaled beclomethasone dipropionate (BDP) on the thickness of basement membrane
      and cellular infiltration into the bronchial mucosa, and the expression of growth
      factors in patients with asthma. METHODS: We studied bronchial biopsies from 24
      asthmatic patients before and after treatment with inhaled BDP, 400 microg twice
      a day or placebo, for 6 months in a double-blind manner. Each subject recorded
      daily asthma symptoms and peak expiratory flow (PEF). Lung function and bronchial
      responsiveness to methacholine were measured before and after treatment. The
      thickness of the basement membrane was determined by electron microscopy.
      Inflammatory cells and the expression of growth factors were examined by
      immunohistochemistry in endobronchial biopsy specimens. RESULTS: After 6 months
      of treatment, we observed a significant improvement of asthma symptoms (P<0.01),
      PEF (P<0.01), diurnal variation of PEF (P<0.05), and airway responsiveness (P<
      0.05) in the BDP group compared with the placebo group. This was accompanied by a
      significant decrease in the thickness of the lamina reticularis (P < 0.001), and
      in the number of activated eosinophils (P<0.01), T-lymphocytes (P<0.01), and
      fibroblasts (P < 0.05) in BDP-treated patients. There was also a reduction in the
      expression of insulin-like growth factor (IGF)-I (P < 0.01). Significant
      correlation was found between the IGF-I expression and collagen thickening (rs =
      0.34, P<0.01), and the number of fibroblasts (rs = 0.45, P < 0.01). CONCLUSION:
      These results suggest that corticosteroid treatment in asthma can reduce the
      lamina reticular thickness by modulation of IGF-I expression with consequent
      inhibition of the airway infiltration by inflammatory cells, and therefore may
      help to prevent remodelling of the airways.

PMID- 9645594
TI  - Association of polymorphisms within the tumour necrosis factor (TNF) genes and
      childhood asthma.
AB  - BACKGROUND: Tumour necrosis factor alpha (TNFalpha) is a potent modulator of
      immune and inflammatory responses, and has been implicated in a variety of
      autoimmune diseases, including asthma. Increased levels of TNFalpha have been
      detected in both sputa and bronchoalveolar lavage fluid of asthmatic subjects
      during acute attacks. Interindividual variation in TNFalpha levels may be
      genetically determined and polymorphisms within the TNF genes and nearby HLA
      Class II region have been associated with differences in TNFalpha production.
      OBJECTIVE: To investigate the association of differences in asthma-related
      phenotypes with two biallelic polymorphisms: a G to A substitution at position -
      308 of the TNFalpha gene promoter (TNF1 and TNF2 alleles) and an NcoI
      polymorphism in the first intron of the lymphotoxin alpha gene (LT-alpha*1 and LT
      alpha*2 alleles). METHODS: The regions of interest were amplified from genomic
      DNA using specific primers and PCR. Dot blot analysis was used for genotyping
      individuals for the TNFalpha - 308 polymorphism, while restriction enzyme
      digestion was used for genotyping individuals for the LT-alpha gene NcoI
      polymorphism. A case-control analysis was then performed on 74 asthmatic and 50
      non-asthmatic unrelated children for each polymorphism. RESULTS: The TNFalpha -
      308 TNF1 allele was present at a significantly higher frequency in cases than
      controls (OR= 2.4, P=0.003), and homozygosity for the TNF1 allele was associated
      with a fivefold increased risk of physician diagnosed asthma relative to the
      other genotypes (OR = 5.23, P = 0.004). The LT-alpha*2 allele showed similar
      associations, including an approximately fivefold higher risk of physician
      diagnosed asthma for LT-alpha*2 homozygotes (OR = 4.89, P = 0.019). Evidence of a
      significant linear trend in asthma risk across the three genotypes was found for
      both polymorphisms. CONCLUSION: These results suggest an important role for the
      TNFalpha gene or a linked locus in an inherited asthma diathesis.

PMID- 9645595
TI  - Indoor environment of residential homes in Hong Kong--relevance to asthma and
      allergic disease.
AB  - BACKGROUND: The prevalence of asthma and allergic disease has been increasing in
      Hong Kong and environmental factors are thought to play a major role. AIM: To
      define the distribution of common inhaled allergens and air pollutants inside
      residential homes in Hong Kong. METHODS: Forty randomly selected residential
      homes were visited and surveyed. Dust samples were collected from mattress,
      bedroom floor, lounge room floor and kitchen floor for assays of Der p 1, Fel d
      1, and Bla g 2. Nitrogen dioxide (NO2) levels were measured by stationary
      samplers left in the bedroom, lounge room and kitchen over a 1-week period.
      RESULT: All 40 homes were apartments in high-rise buildings and the mean age of
      the homes was 7.6 +/- 4.8 years. Visible dampness and mould patches were present
      in 27.5% of homes and the main fuel for cooking was gas (97.5%). Der p 1, Fel d 1
      and Bla g 2 were detectable in at least 1 niche in over 85% of homes. In
      particular, all dust samples from mattress and bedroom floor contained Der p 1,
      and over 50% had levels > or = 2 microg/g. The (geometric) mean Der p 1 level in
      mattress dust was 8.8 (0.3-157.8) microg/g. Fel d 1 and Bla g 2 were present in
      low levels throughout the homes with respective (geometric) means of 0.3 (0-3.7)
      microg/g and 0.1 (0-1.1) Unit/g in mattress dust. NO2 was readily detected in all
      niches but the highest level was in the kitchen with mean exposure of 48.7 ppb
      which was 1.5 times higher than that in the bedroom and lounge room. CONCLUSION:
      Major allergens of mite, cat and cockroach, and NO2 are present in varying
      quantities in residential homes in Hong Kong. Exposure to these environmental
      factors could be important in the development of asthma and allergic diseases in
      susceptible individuals.

PMID- 9645596
TI  - Atopy in children with otitis media with effusion.
AB  - BACKGROUND: Contrasting data have been found on the prevalence of atopy in
      children with otitis media with effusion (OME). A major issue would be to
      determine whether screening for atopy should be recommended. Setting Centre for
      Study of Otitis Media with Effusion, Tabiano Terme, Parma, Italy. OBJECTIVE: The
      purpose of this study was to investigate the relation of OME to atopy. METHODS:
      The subjects were 172 children with OME and a control group of 200 children. The
      protocol included a questionnaire survey of diseases associated with atopy, a
      skin-prick test and a clinical evaluation of allergic symptoms and
      hypersensitivity to aeroallergens. RESULTS: No significant difference between
      patients and control group was observed for family history of atopy or positive
      skin-prick test reactions. Symptoms associated with atopy occurred significantly
      more frequently in the group with OME (P<0.001), though only the presence of
      rhinitis or atopic eczema was significantly associated with OME. CONCLUSIONS:
      Prevalence of positive skin-prick tests results is not enhanced in children with
      OME. Nevertheless, the association of OME with symptoms associated with atopy
      suggests that such concomitant diseases may play a part in the pathogenesis of
      the disorder. Children with allergic rhinitis or atopic eczema should be
      investigated by tympanometry for OME.

PMID- 9645597
TI  - Increased nitric oxide in nasal lavage fluid and nitrotyrosine formation in nasal
      mucosa--indices for severe perennial nasal allergy.
AB  - BACKGROUND: The nose contributes the large amount of nitric oxide (NO) to exhaled
      air. NO is a mediator of vasodilation and yields peroxynitrite (ONOO-) by
      reacting with superoxide (O2-). ONOO attacks tyrosine residues to form
      nitrotyrosine. OBJECTIVE: The aim of this study was to examine the
      pathophysiological role of NO in nasal mucosa in patients with perennial nasal
      allergy. METHODS: We measured nitrite and nitrate (NO2-/NO3-) and 3',5'-guanosine
      monophosphate (cyclic GMP) in nasal lavage fluid, and also measured haemoglobin
      concentration in nasal mucosa as an indicator of blood volume in the patients and
      healthy volunteers. The deleterious role of NO was also investigated by measuring
      nitrotyrosine in nasal mucosa. RESULTS: The NO2-/NO3- concentration in the nasal
      lavage fluid was 39.5+/-2.8 microM in healthy volunteers (n=40), 42.4+/-3.0
      microM in patients with mild allergy (mild group, n=32), and 88.7+/-6.6 microM in
      patients with severe allergy (severe group, n=61). In the patients whose symptoms
      were improved with treatment, NO2-/NO3- levels decreased to 45.7+/-10.4 microM.
      The concentration of cyclic GMP in nasal lavage fluid was higher in the severe
      group than in the healthy volunteers. The mucosal haemoglobin index was 88+/-4 in
      the healthy volunteers, 67+/-4 in the mild group, and 53+/-2 in the severe group.
      The formation of nitrotyrosine was expressed 0.58+/-10% to total tyrosine in the
      severe group (n=11), but was not found in non-allergy patients (n=9).
      CONCLUSIONS: The production of NO was increased in patients with perennial nasal
      allergy, but the blood flow in the nasal mucosa of patients was reduced.
      Nitrotyrosine formation suggests that there is a process of ONOO(-)-induced
      damage in mucosa of patients with the perennial nasal allergy and this damage may
      limit the dilatation of blood vessels, despite the presence of excessive NO.

PMID- 9645598
TI  - CD11b and L-selectin expression on eosinophils and neutrophils in blood and
      induced sputum of patients with asthma compared with normal subjects.
AB  - BACKGROUND: Patients with asthma show altered surface expression of the adhesion
      molecules CD11b and L-selectin on airway granulocytes compared with blood
      granulocytes. OBJECTIVE: To investigate whether this modulation is related to
      disease activity or due to transendothelial migration, we compared the CD11b and
      L-selectin expression on blood and induced sputum eosinophils and neutrophils
      between patients with asthma and normal subjects. METHODS: Eleven normal subjects
      (21-43 years), nine patients (21-34 years) with mild atopic asthma and 10
      patients (20-47 years) with moderate to severe atopic asthma on regular treatment
      with inhaled steroids underwent sputum induction by inhalation of nebulized
      hypertonic saline (4.5%). CD11b and L-selectin expression on granulocytes from
      blood and DTT-homogenized sputum were analysed by flow cytometry. Eosinophils
      could be discriminated from neutrophils by using depolarized light scatter.
      Disease activity was assessed by baseline FEV1 and airway responsiveness to
      histamine (PC20). RESULTS: Sputum eosinophils showed higher expression of CD11b
      (P<0.001) and lower expression of L-selectin (P<0.001) compared with peripheral
      blood eosinophils. CD11b and L-selectin expression on eosinophils from blood or
      sputum did not differ between the three groups. Similar results were obtained for
      neutrophils. The PC20 in the patients with moderate-to-severe asthma was related
      to CD11b expression on blood (R=-0.92, P=0.001) and sputum eosinophils (R=0.75,
      P=0.02). CONCLUSIONS: Flow cytometry of induced sputum granulocytes from
      asthmatic as well as normal subjects is feasible. We conclude that the modulated
      expression of CD11b and L-selectin on airway granulocytes is not specific for
      asthmatic airway inflammation, but is probably the result of tissue migration per
      se. This implies that CD11b and L-selectin expression on granulocytes in induced
      sputum cannot be used as marker of disease activity.

PMID- 9645599
TI  - Regulation of interleukin-8 binding and function by heparin and alpha2
      macroglobulin.
AB  - BACKGROUND: Increased expression of interleukin-8 (IL-8), a potent neutrophil
      chemoattractant, is associated with a number of inflammatory diseases.
      Interleukin-8 binds to the glycosaminoglycan (GAG) heparin and the protease
      inhibitor alpha2-macroglobulin, molecules which regulate the function of a number
      of cytokines. Heparan sulphate was previously shown to enhance neutrophil
      chemotactic responses to IL-8. OBJECTIVE: The purpose of this study was to
      investigate the effect of heparin, heparan sulphate and alpha2-macroglobulin on
      IL-8 binding to neutrophils and subsequent functional effects in vitro. METHODS:
      The binding of 125I-IL-8 to normal neutrophils at 4 degrees C was studied and the
      IL-8 induced neutrophil chemotactic response was investigated using micro-Boyden
      chambers. Complexation of IL-8 with alpha2-macroglobulin was confirmed using gel
      filtration chromatography. RESULTS: Heparin, but not heparan sulphate, inhibited
      the binding of 125I-IL-8 to neutrophils (IC50=26 microg/mL) and IL-8 induced
      neutrophil chemotactic responses (IC50=4 microg/mL). The specific inhibitory
      effect of heparin was apparently due to an interaction with IL-8 which was charge
      dependent, since dextran sulphate had a greater inhibitory effect on chemotactic
      responses (IC50=2 microg/mL) and FITC-heparin did not bind to neutrophils. The
      heparin-induced inhibition of IL-8 binding and chemotactic responses was reversed
      in a dose-dependent manner in the presence of alpha2-macroglobulin. The binding
      of 125I-IL-8 to neutrophils in the presence of alpha2-macroglobulin appears to
      be, in part, through the specific IL-8 receptor. CONCLUSION: These results point
      to an anti-inflammatory role for heparin and a novel, potentially, pro
      inflammatory role for alpha2-macroglobulin which together indicate the importance
      of cytokine-binding macromolecules in determining net cytokine function.

PMID- 9645600
TI  - Various immunological phenotypes are associated with increased airway
      responsiveness.
AB  - BACKGROUND: Bronchial asthma is characterized by a TH2 type immune response,
      chronic inflammation of the airways and increased airway responsiveness. The
      relationship between IgE- and inflammatory-dependent mechanisms that contribute
      to bronchial asthma are not well defined. OBJECTIVE: The purpose of this study
      was to compare and analyse the immune pathways that resulted in development of
      allergen-induced and/or inflammatory dependent increased airways responsiveness.
      RESULTS: BALB/c and C57BL/6 mice responded to OVA-sensitization with elevated
      allergen-specific IgE/IgG1 serum antibody-titres and the development of cutaneous
      immediate-type hypersensitivity reactions. Increased airway responsiveness was
      observed following airway allergen challenges. However, the inflammatory
      component of the lung differed between the strains. In OVA-sensitized BALB/c mice
      a marked increase in lymphocytes, eosinophils and neutrophils in BAL fluids was
      parallelled with elevated production of IL-4, IL-5 and TNFalpha in the lung. In
      contrast in OVA-sensitized C57BL/6 mice, the inflammatory immune response in the
      lung was much weaker. We postulate that two pathways can regulate the induction
      of increased airway responsiveness. One depends on the presence of allergen
      specific IgE/IgG1 and allergen, and a second is mediated by allergen-independent
      inflammation of the lung. To test this hypothesis, BALB/c mice were treated
      nasally with low doses of bacterial superantigen (SEB) as a prototypical inducer
      of airway inflammation, following which influx of lymphocytes, eosinophils and
      neutrophils into the airways was parallelled by development of increased airway
      responsiveness in the absence of allergen-specific IgE/IgG1 antibodies and
      allergen. CONCLUSIONS: These results indicate that increased airway
      responsiveness is associated with different immunological phenotypes in BALB/c
      and C57BL/6 mice.

PMID- 9645601
TI  - Inhibitory effect of NPC-17731 on BK-induced and antigen-induced airway reactions
      in guinea-pigs.
AB  - BACKGROUND: Bradykinin (BK) has been suggested to act as a mediator in the
      airways in inflammatory conditions, such as asthma through the activation of B2
      receptors. NPC-17731 (D-Arg0[Hyp3, D-HypE(trans-propyl)7, Oic8]BK) has potent
      antagonistic activity against B2-receptors without agonistic activity. OBJECTIVE:
      We have evaluated the inhibitory effect of NPC-17731 against BK in guinea-pig
      airways. In addition, we have investigated the effects of NPC-17731 on antigen
      induced airway responses. METHODS: Bronchoconstriction was assessed as an
      increase in lung resistance (RL) and a decrease in dynamic compliance (Cdyn).
      Airway plasma leakage was assessed by extravasation of intravenously injected
      Evans blue dye. To estimate the effect of drugs on antigen-induced reactions,
      guinea-pigs were actively sensitized by exposure to aerosol ovalbumin (OA) twice
      and challenged by OA inhalation. Acute bronchoconstriction was measured for 15
      min. Airway vascular leakage was measured at 10 min after the challenge.
      Assessment of airway hyperresponsiveness against acetylcholine and
      bronchoalveolar lavage were conducted at 18-24 h after the antigen-challenge.
      RESULTS: NPC-17731 (0.3-30 microg/kg, i.v.) inhibited intravenously applied BK
      induced bronchoconstriction in a dose-dependent manner. The 50% inhibitory doses
      (ID50) were 1.3 microg/kg for RL and 2.8 microg/kg for Cdyn. NPC-17731 (1-10
      microg/kg, i.v.) inhibited BK-induced microvascular leakage in a dose-dependent
      manner (ID50 = 4.2 microg/kg). In addition, 10 microg/kg of NPC-17731 abolished
      the inhaled BK-induced bronchoconstriction. In the sensitized animals, 100
      microg/kg NPC-17731 significantly reduced the airway microvascular leakage and
      the decrease in Cdyn induced by ovalbumin exposure (P < 0.05), but did not
      influence the increase in RL. NPC-17731 (100 microg/kg) inhibited the antigen
      induced airway hyperresponsiveness and the increase in eosinophils in BAL fluids.
      CONCLUSION: These results indicate that NPC-17731 is a potent BK antagonist in
      vivo and that BK may partially contribute to the antigen-induced airway responses
      in guinea-pigs.

PMID- 9645602
TI  - Inhaled procaterol inhibits histamine-induced airflow obstruction and
      microvascular leakage in guinea-pig airways with allergic inflammation.
AB  - BACKGROUND: Beta2-adrenoceptor agonists (beta2-agonists) are shown to inhibit
      airway microvascular leakage in experimental animals. This effect may change in
      animals with chronic airway inflammation. OBJECTIVE: We examined whether inhaled
      beta2-agonists inhibit microvascular leakage in guinea-pig airways with chronic
      allergic inflammation. METHODS: Three weeks after the sensitization with
      ovalbumin (OA; 6 mg/mL), each guinea pig was challenged with inhaled OA once a
      day for 1 or 3 weeks. Control animals without sensitization with OA also inhaled
      vehicle for OA (saline) for 3 weeks. One day after the last challenge, different
      doses of inhaled procaterol (1, 3 or 10 microg/mL) or vehicle was given to
      animals for 10 min after an anaesthesia. Fifteen minutes after the end of
      inhalation, the animals were given i.v. Evans blue dye (EB dye; 20 mg/kg), a
      marker of microvascular leakage, and then i.v. histamine (3 or 30 microg/kg) or
      vehicle. Lung resistance, a parameter of airflow obstruction, was measured for 6
      min and the lungs were removed to calculate the amount of extravasated EB dye
      into the airways. RESULTS: A significant increase in eosinophil infiltration into
      the airways was seen in sensitized and challenged animals compared with control
      animals without sensitization. Among animals receiving antigenic exposure for
      either 0 (control), 1 or 3 weeks, 10 microg/mL procaterol significantly inhibited
      30 microg/kg histamine-induced increase in EB dye extravasation to a similar
      degree (ranged from 28.7 to 69.8% inhibition) as well as that in lung resistance
      (more than 90% inhibition in all groups). The minimal dose of procaterol to
      inhibit 3 microg/kg histamine-induced microvascular leakage was not different
      between nonsensitized control animals and those sensitized and challenged for 3
      weeks at all airway levels. CONCLUSION: Inhaled beta2-adrenoceptor agonists may
      be also potent in attenuating microvascular leakage even in the airways with
      chronic allergic inflammation.

PMID- 9645603
TI  - Regulation of Vbeta germline transcription in RAG-deficient mice by the
      CD3epsilon-mediated signals: implication of Vbeta transcriptional regulation in
      TCR beta allelic exclusion.
AB  - During the thymic development of alphabeta lineage T cells, maturation of the CD4
      CD8- double-negative (DN) cells into the CD4+ CD8+ double-positive cells is
      accompanied by the induction of TCR beta allelic exclusion. Recent studies have
      shown that these events are regulated by the signals through the pre-TCR complex
      which consists of the TCR beta, pre-TCR alpha and CD3 components. The Vbeta
      germline transcripts are detected prior to the TCR beta chain gene rearrangements
      in the DN thymocytes. To examine the effects of the pre-TCR-mediated signals on
      Vbeta germline transcription, we analyzed thymocytes from RAG-2-deficient mice
      treated with anti-CD3epsilon antibody. The germline transcripts of all Vbeta we
      examined, except for Vbeta14, were down-regulated by the anti-CD3epsilon antibody
      treatment. These data indicate that the regulation of Vbeta germline
      transcription by the signals through the pre-TCR complex may reflect the
      modulation of Vbeta accessibility to the VDJ recombinase, which contributes to
      TCR beta allelic exclusion.

PMID- 9645604
TI  - Prolongation of allograft survival by administration of mAb specific for the
      three subunits of IL-2 receptor.
AB  - The IL-2 receptor (IL-2R) gamma chain, the so-called common gamma (gamma(c))
      chain, which is shared with multiple cytokine receptors, plays important roles in
      the immune system. Here we assessed the immunosuppressive ability of mAb specific
      for the gamma(c) chain in induction of cytotoxic T lymphocytes (CTL) and
      allograft rejection in combination with mAb specific for the alpha and beta
      chains of IL-2R. CBA/N (H-2k) mice were injected i.p. with allogeneic splenocytes
      from BALB/c (H-2d) mice, and then administered with combinations of anti-IL-2R
      alpha, anti-IL-2R beta and anti-gamma(c) mAb or a control mAb. Addition of anti
      gamma(c) mAb together with anti-IL-2R alpha and anti-IL-2R beta mAb induced a
      complete inhibition of CTL response. The numbers and populations of CD4+ CD8- and
      CD4- CD8+ T cells were not significantly affected by administration of the three
      anti-IL-2R mAb, whereas NK cells were completely depleted in spleens of mice
      treated with the anti-IL-2R mAb. Furthermore, skin allograft survival was also
      significantly prolonged by administration of the three anti-IL-2R mAb. These
      results suggest that the anti-gamma(c) mAb in combination with anti-IL-2R alpha
      and anti-IL-2R beta mAb is capable of suppressing induction of CTL and NK cells,
      resulting in prolongation of skin allograft survival.

PMID- 9645605
TI  - In vitro and in vivo selectin-blocking activities of sulfated lipids and sulfated
      sialyl compounds.
AB  - There is accumulating evidence that sulfated lipids, sulfated oligosaccharides
      and other sulfated compounds are reactive with selectins in a manner that
      interferes with selectin interactions with their natural ligands. In the report
      we describe the ability of sulfated lipids (sulfatides and gangliosides) and
      multimeric forms of sulfated sialic acid to block binding of P- and E-selectin-Ig
      to neutrophils. The in vivo ability of these compounds to block lung injury in
      rats following i.v. infusion of purified cobra venom factor (CVF), which induces
      injury that is L- and P-selectin dependent, was also determined as well as
      effects on recruitment of neutrophils, as measured by lung myeloperoxidase. There
      was a significant correlation between the ability of sulfated lipids and sialyl
      compounds to interfere in vitro with P-selectin-Ig binding to neutrophils and to
      protect against P-selectin-dependent acute lung injury induced by CVF. The
      biological effects of these sulfated compounds were also associated with
      diminished accumulation of neutrophils. The protective effects of these compounds
      may be linked to their ability to interfere with P-selectin binding to counter
      receptors on neutrophils.

PMID- 9645606
TI  - Requirement for p56(lck) tyrosine kinase activation in Th subset differentiation.
AB  - The lymphocyte-specific protein tyrosine kinase p56(lck) (Lck) is well documented
      with regard to its role in regulating T cell activation and thymocyte development
      through delivery of signals via the mature alphabeta TCR as well as the pre-TCR.
      Little is known, however, about the role of Lck in Th cell subset differentiation
      in the periphery. Here, we assess the requirement for tyrosine kinase activation
      of Lck in Th1 and Th2 cell differentiation by using a dominant-negative Lck
      (DLGKR) transgenic (Tg) mice under the control of a lck distal promoter that
      directs high expression in mature T cells, in which splenic CD4 T cells developed
      normally. This Tg mouse provides a good experimental model system to investigate
      the roles of Lck in mature T cell function in vivo. We show that the
      catalytically inactive Lck protein at about twice-normal concentrations inhibits
      Th2 subset differentiation in vivo and in vitro, whilst leaving the maturation of
      the other T cell subset, Th1, intact. These data indicate a requirement for Lck
      activity in Th2 cell differentiation, and a differential dependence for Lck
      activity between Th2 and Th1 cell differentiation.

PMID- 9645607
TI  - Dexamethasone enhances macrophage colony stimulating factor- and granulocyte
      macrophage colony stimulating factor-stimulated proliferation of bone marrow
      derived macrophages.
AB  - Glucocorticoids are effective repressors of the immune system. We have examined
      the effect of glucocorticoids on the proliferation of murine macrophages.
      Dexamethasone by itself did not affect proliferation of differentiated or
      undifferentiated bone marrow-derived macrophages (BMM) and elicited peritoneal
      macrophages. However, dexamethasone enhanced the proliferation induced by
      macrophage colony stimulating factor (M-CSF) of these cells. The effect of
      dexamethasone was not restricted to M-CSF-dependent proliferation. Similarly,
      dexamethasone enhanced granulocyte macrophage colony stimulating factor (GM-CSF)
      dependent proliferation of BMM. In agreement, macrophages transfected with the
      glucocorticoid receptor showed an enhancement of M-CSF-dependent proliferation.
      The enhancement of proliferation by dexamethasone or the glucocorticoid receptor
      was abolished by RU 486, an antagonist of the glucocorticoid receptor. Moreover,
      the addition of antibodies against M-CSF inhibits the effect of dexamethasone,
      suggesting that dexamethasone increases the autocrine production of M-CSF. This
      only occurs when M-CSF or GM-CSF, which induce M-CSF, are present in the media.
      In tissues, dexamethasone may enhance macrophage proliferation and contribute to
      the resolution of the inflammatory states.

PMID- 9645608
TI  - Regulation by transforming growth factor-beta1 of class II mRNA and protein
      expression in fibroblast-like synoviocytes from patients with rheumatoid
      arthritis.
AB  - Transforming growth factor (TGF)-beta1 is an immunosuppressive cytokine that
      modulates the expression of class II histocompatibility antigens on human cells.
      Aberrant HLA class II expression on synovial lining cells of rheumatoid arthritis
      synovial membrane has been described, and the extent and intensity of class II
      expression on the cells was claimed to be linked with the severity of the
      disease. In this study, the effects of TGF-beta1 on HLA class II antigen
      expression in fibroblast-like synoviocytes (SFC) from rheumatoid synovectomy
      tissues were determined by flow cytometric analysis and quantitative RT-PCR. We
      found that pre-incubation of cells with TGF-beta1 was able to down-regulate IFN
      gamma-induced DR protein expression in SFC. TGF-beta1, additionally, down
      regulated IFN-gamma-stimulated class II transactivator (CIITA) and DRB mRNA
      expression. The constitutive expression of CIITA mRNA was completely abolished
      and the constitutive expression of DRB mRNA was decreased after treatment of SFC
      with TGF-beta1 for 24 h. Addition of the TGF-beta inhibitor decorin to SFC for 24
      h before TGF-beta1/IFN-gamma treatment was able to reduce the down-regulatory
      effect of TGF-beta1 on DR antigen expression induced by IFN-gamma. Using
      competitive RT-PCR, we found that SFC constitutively expressed decorin mRNA and
      that treatment of cells with TGF-beta1 for 24 h reduced the constitutive
      expression of decorin mRNA by 65%. Our results show that TGF-beta1 is able to
      reduce the expression of HLA class II mRNA and protein, and suggest a tight
      regulation between TGF-beta1 and decorin in SFC of the rheumatoid synovium.

PMID- 9645609
TI  - Hsp72-mediated augmentation of MHC class I surface expression and endogenous
      antigen presentation.
AB  - Efficient recognition of tumor cells by cytolytic T lymphocytes (CTL) is often
      dependent on the presentation of cytosolic peptides in the context of MHC class I
      molecules. This process may be influenced by various molecular chaperones. To
      analyze this influence, we have utilized B16 melanoma cells, which are not
      effectively recognized by MHC class I-restricted CTL. This resistance to CTL is
      apparently due to a very low level of surface MHC expression. We have found that
      stably transfected clones of B16 which constitutively express the human heat
      shock protein 72 (Hsp72) exhibit significantly increased levels of MHC class I
      antigens on their surface. This Hsp72-mediated up-regulation of surface MHC class
      I antigen represents an increase in the amount of functional MHC-peptide
      complexes as measured by conformation-dependent antibodies and recognition by MHC
      class I-restricted CTL. Expression of Hsp72 did not improve the antigen
      presentation defect in cells lacking the activity of the transporter associated
      with antigen presentation (TAP). Moreover, mice immunized with Hsp72-expressing
      B16 cells, but not with control-transfected B16 cells, display significantly
      increased resistance to a subsequent challenge with live, wild-type B16.
      Together, our data demonstrate that the immune recognition of tumor cells can be
      substantially enhanced by the suitable expression of a molecular chaperone.

PMID- 9645610
TI  - Role of co-stimulation in CD8+ T cell activation.
AB  - The two-signal model states that activation of naive T cells requires a signal 1
      stimulus through the TCR and a co-stimulatory signal 2. By contrast, signal 1
      alone is sufficient for pre-activated T cells. Recently, however, it has been
      shown that under certain conditions T cells can bypass the requirement for co
      stimulation. For example, CD28-deficient mice, when immunized with lymphocytic
      choriomeningitis virus, mount a vigorous cytotoxic T lymphocyte response and
      clear the virus. As a continuous effort to unravel the mechanisms of T cell
      activation, we previously reported activation of hybridoma T cells by recombinant
      single-chain MHC molecules in the absence of antigen-presenting cells. In such
      reconstitution experiments, since the signals delivered to the T cells are well
      controlled, the contribution of any known or unknown signals can be ruled out. In
      the present study, we analyzed the requirements for activation of naive T cells
      by using splenocytes from TCR transgenic mice as a source of responding cells. We
      observed that naive CD8+ T cells are fully activated by signal 1 alone, but that
      co-stimulation lowers their activation threshold. Previously activated T cells
      are fully responsive, even when the first stimulation was performed in the
      absence of co-stimulation. They display a low activation threshold and are
      insensitive to co-stimulation. The physiological relevance of this finding and
      its consequences for immunotherapy as well as for our understanding of self
      tolerance are discussed.

PMID- 9645611
TI  - Multiple gene duplication and expression of mouse bcl-2-related genes, A1.
AB  - Here we report the genomic cloning and characterization of the murine A1 genes,
      which belong to the bcl-2 gene family. Southern analysis indicated the existence
      of at least four A1 genes in the murine genome and four different A1 genes,
      designated A1-a, -b, -c and -d, were cloned from the murine genomic library. The
      A1-a, -b and -d genes consisted of two exons, whereas the A1-c gene contained 1
      bp insertion in the coding region which may result in an aberrant and truncated
      protein by frame-shift. With the exception of A1-c, the coding regions among A1
      genes are highly conserved at >97% at the nucleotide level and at >96% at the
      amino acid level. A1-a, -b and -d genes appeared to be expressed specifically in
      organs containing many neutrophils. In neutrophils, A1-a, -b and -d transcripts
      were detected at a comparable level. Our data suggest that the multiple A1 genes
      in mice were generated by gene duplication and each of them may function as anti
      apoptotic molecules in neutrophils.

PMID- 9645612
TI  - A functional epitope on P-selectin that supports binding of P-selectin to P
      selectin glycoprotein ligand-1 but not to sialyl Lewis X oligosaccharides.
AB  - P-selectin mediates the adhesion of leukocytes to activated platelets and
      endothelial cells. To characterize the functional domains of P-selectin for
      ligand recognition, we established nine hybridoma cell lines secreting anti-rat P
      selectin mAb. Among them, the mAb C215 bound both rat and human P-selectins, and
      inhibited binding of rat and human P-selectins to P-selectin glycoprotein ligand
      1 (PSGL-1) from HL-60 cells. In contrast, mAb C215 failed to inhibit the binding
      of rat and human P-selectin-IgG to sialyl Lewis X (sLe(x)) oligosaccharides.
      Epitope mapping of mAb C215 using synthetic decapeptides revealed that mAb C215
      binds specifically to an eight-residue epitope that spans amino acids 76-83 of
      rat P-selectin, a region completely conserved by human P-selectin. Synthetic
      peptides containing the mAb C215 epitope inhibited binding of P-selectin to PSGL
      1, but not to sLe(x) oligosaccharides, suggesting that the C215 epitope on P
      selectin may directly interact with a particular site on the PSGL-1 core protein
      essential for interaction with P-selectin, such as sulfated tyrosine residues.
      Our results suggest the presence of two ligand recognition sites on P-selectin
      necessary for binding to PSGL-1--one recognizes sLe(x), while the other
      recognises the PSGL-1 core protein.

PMID- 9645613
TI  - Pertussis toxin potentiates Th1 and Th2 responses to co-injected antigen:
      adjuvant action is associated with enhanced regulatory cytokine production and
      expression of the co-stimulatory molecules B7-1, B7-2 and CD28.
AB  - Pertussis toxin (PT) is a major virulence factor of Bordetella pertussis which
      exerts a range of effects on the immune system, including the enhancement of IgE,
      IgA and IgG production, delayed-type hypersensitivity reactions, and the
      induction of experimental autoimmune diseases. However, the mechanism by which PT
      mediates adjuvanticity remains to be defined. In this investigation we have shown
      that PT can potentiate antigen-specific T cell proliferation and the secretion of
      IFN-gamma, IL-2, IL-4 and IL-5 when injected with foreign antigens. A chemically
      detoxified PT and a genetic mutant with substitutions/deletions in the S-1 and B
      oligomer components that abrogate enzymatic and binding activity displayed no
      adjuvant properties. In contrast, a non-toxic S-1 mutant devoid of enzymatic
      activity but still capable of receptor binding retained its adjuvanticity,
      augmenting the activation of both Th1 and Th2 subpopulations of T cells. In an
      attempt to address the mechanism of T cell activation, we found that PT
      stimulated the production of IFN-gamma and IL-2 by naive T cells and IL-1 by
      macrophages. Therefore potentiation of distinct T cell subpopulations may have
      resulted in part from the positive influence of IFN-gamma on the development of
      Th1 cells and the co-stimulatory role of IL-1 for Th2 cells. Furthermore, PT
      augmented expression of the co-stimulatory molecules B7-1 and B7-2 on macrophages
      and B cells, and CD28 on T cells, suggesting that the adjuvant effect may also be
      associated with facilitation of the second signal required for maximal T cell
      activation. This study demonstrates that the immunopotentiating properties of PT
      are largely independent of ADP-ribosyltransferase activity, but are dependent on
      receptor binding activity and appear to involve enhanced activation of T cells.

PMID- 9645614
TI  - The reactivity pattern of hemagglutinin-specific clonotypes from mice immunized
      as neonates or adults with naked DNA.
AB  - In contrast to adult mice immunized with influenza A virus strain WSN and plasmid
      expressing WSN hemagglutinin (HA) gene which developed primary and secondary anti
      HA antibody responses, mice immunized as neonates with virus failed to produce
      anti-HA antibodies while those immunized with plasmid developed weak primary but
      strong secondary responses. Analysis of the frequency of HA-specific B clonotypes
      as well as their reactivity pattern (RP) showed that viral or genetic
      immunization of adults increased the frequency of clonotypes which exhibit broad
      RP. The most striking observation of our study is that immunization of neonates
      with plasmid leads to increased synthesis of anti-HA antibodies as well as to an
      increased frequency of clonotypes exhibiting an adult-like RP. In contrast,
      neonatal immunization with virus caused a long-lasting unresponsiveness and the
      few clonotypes stimulated in vitro exhibited only a monoreactive pattern. Isotype
      patterns of mAb are also diversified in the case of mice immunized with plasmid
      as neonates. Rapid replacement of neonatal with adult clonotypes may explain the
      significant survival of the mice immunized with plasmid and challenged 1 or 3
      months later with lethal doses of virus.

PMID- 9645615
TI  - Predominant usage of the proximal poly(A) site in alpha mRNAs is not intrinsic to
      the 3' termini.
AB  - The maturation of IgM-expressing B cells to IgM-secreting plasma cells is
      associated with both an increase in mu mRNA and the ratio of secreted to membrane
      forms of mu mRNA. In contrast, previous studies demonstrated that in vitro the
      secreted form of alpha mRNA (alpha s mRNA) predominates regardless of the stage
      of B cell differentiation. The present study demonstrates that alpha s mRNA
      predominates in both B cells derived from the germinal centers of murine Peyer's
      patches and in the functional IgA memory population, suggesting that in vitro
      events accurately represent the generation of a secretory IgA response in vivo.
      Although the predominant usage of the alpha s poly(A) site is due to RNA
      processing, it does not depend on either the alpha s poly(A) site, the 3' splice
      site associated with the exon encoding the membrane exon of IgA (alphaM) or the
      alphaM poly(A) sites. Analysis of the sequence of the intron between the alpha s
      terminus and alphaM (alpha s-alphaM intron) demonstrates the existence of several
      potential regulatory elements. Furthermore, the effects of deletions within the
      alpha s-alphaM intron on 3' terminus usage demonstrate that the predominant usage
      of the proximal terminus is not strictly dependent on the length of the intron.
      Together with previous work, these observations support the idea that choice of
      3' terminus for all Ig heavy chain genes is regulated by a similar mechanism, but
      specific sequences within a heavy chain gene can impinge upon that mechanism.

PMID- 9645616
TI  - Soluble human lymphocyte activation gene-3 modulates allospecific T cell
      responses.
AB  - Lymphocyte activation gene (LAG)-3, a member of the Ig superfamily, has been
      characterized as an activation antigen of T cells and NK cells. LAG-3 has been
      proposed as an alternate ligand for HLA class II due to some sequence homology
      and similarities in exon-intron organization with CD4. Here, we report the
      functional evaluation of a soluble Ig fusion molecule of human LAG-3 (LAG-3-Ig)
      in T cell activation assays. Cytofluorimetry studies revealed LAG-3-Ig binding
      predominantly to class II-expressing cells. In functional assays, inhibition of
      primary allogeneic mixed lymphocyte response (MLR) and murine-human xenogeneic
      MLR was observed in the presence of LAG-3-Ig. Effects of LAG-3-Ig addition were
      not observed on mitogen-, recall antigen- or superantigen-mediated stimulation.
      Cytotoxic T lymphocyte effector functions were also not affected by LAG-3-Ig.
      Inhibition of alloresponses by LAG-3-Ig occurred within the first 24 h of
      activation, resulting in a strong inhibition of IL-2 production. Unlike blockade
      of the CD28 receptor, however, LAG-3-Ig-mediated inhibition could not be reversed
      by exogenous IL-2 supplementation. Cytofluorimetric analysis of the phenotype of
      cells exposed to LAG-3-Ig in MLR cultures revealed a decrease in IL-2 receptor
      expression (CD25) on CD4+ cells in all donors tested. Based on the results from
      these studies, we conclude that LAG-3-Ig inhibits alloresponses of naive
      peripheral blood lymphocytes, by blocking the activation of a subpopulation of
      allo reactive cells.

PMID- 9645617
TI  - Regulation of in vitro and in vivo T cell activation by CD43.
AB  - Accessory molecule interactions can be critical in determining the outcome of a T
      cell's encounter with antigen. Cell adhesion proteins may augment T cell
      responses by facilitating TCR engagement of the antigen-MHC complex, while co
      stimulatory molecules may deliver distinct signals that modulate T cell
      responsiveness. CD43 (leukosialin, sialophorin) has been suggested to influence
      cell activation by steric hindrance based upon the large size and glycosylation
      of the protein, as well as the relative abundance of the protein on the cell
      surface. In this paper we examine both in vitro and in vivo T cell-dependent
      responses in CD43-deficient mice. We demonstrate that T cells from CD43-deficient
      mice are hyper-responsive following both in vivo and in vitro activation, and
      that this is observed in response to not only TCR-CD3-mediated stimulation, but
      also following receptor-independent activation. This data suggests that
      mechanisms other than non-specific steric hindrance are important in the
      regulation of T cell activation by CD43.

PMID- 9645618
TI  - IL-6-deficient mice are resistant to the induction of experimental autoimmune
      encephalomyelitis provoked by myelin oligodendrocyte glycoprotein.
AB  - The role of IL-6 in experimental autoimmune encephalomyelitis (EAE) provoked by
      myelin oligodendrocyte glycoprotein (MOG) was investigated using IL-6-deficient
      mice. We show here that IL-6-deficient mice were resistant to the MOG-induced EAE
      as compared to wild-type mice (one out of 18 versus 17 out of 20). The delayed
      type hypersensitivity response, lymphocyte proliferation response and antibody
      reactivity to MOG in IL-6-deficient mice were significantly lower than those in
      wild-type mice. Furthermore, the histological examination revealed that no
      infiltration of inflammatory cells was observed in the central nervous system of
      IL-6-deficient mice. These results indicate that IL-6 may play a crucial role in
      the induction phase of EAE. Given the potential relevance of this animal model
      for multiple sclerosis (MS), it is possible that anti-IL-6 therapy may be useful
      in the prevention of relapses of MS.

PMID- 9645619
TI  - Surgical therapy for heart failure: care of the patient with partial left
      ventriculectomy.
AB  - Partial left ventriculectomy (PLV) surgery has gained significant attention
      worldwide as a possible alternative to heart transplantation or as a therapy to
      treat heart failure. This procedure offers an attractive choice to patients and
      physicians because of the lack of need for immunosuppressive medications and a
      decrease in the risk of rejection associated with transplantation. PLV surgery is
      currently under investigation in several centers worldwide, but long-term
      outcomes have yet to be definitively evaluated. The Cleveland Clinic Foundation
      began performing PLV surgery in May 1996. Since that time, 57 patients have
      received the procedure with actuarial survival of 82% at 1 year. The purpose of
      this article is to highlight the clinical management of the postoperative PLV
      patient.

PMID- 9645620
TI  - Cardiac surgery and women.
AB  - Coronary heart disease is just as serious a problem for women as it is for men,
      yet historically women have been significantly underrepresented in research
      studies related to the disease and treatment options, including cardiac surgery.
      Cardiac surgery is a proven therapy for the management of coronary heart disease
      in women. Research addressing the physical, psychosocial, and emotional issues
      women face during the preoperative, postoperative, and recovery phases of surgery
      is limited. Nurses play a pivotal role in the education and management of women
      undergoing cardiac surgery and need to be aware of unique issues related to the
      experience. This article reviews the literature pertaining to women's issues
      during the perioperative and recovery phases of cardiac surgery.

PMID- 9645621
TI  - The delirious cardiac surgical patient: theoretical aspects and principles of
      management.
AB  - Delirium, an etiologically nonspecific disorder of consciousness characterized by
      prominent deficits in attention, cognition, and perception, affects more than one
      third of adult cardiac surgical patients. Despite the frequency of occurrence and
      the increased morbidity and mortality associated with it, the diagnosis is
      commonly late or missed, and management is less than optimal. This article
      addresses the recognition and management of delirium. Nurses who develop an index
      of suspicion for the diagnosis and acquire the diagnostic and interventional
      skills required to address this cerebral complication of cardiac surgery may well
      decrease its incidence and severity.

PMID- 9645622
TI  - Outcomes measurement.
AB  - Patient outcomes have been referred to as the "ultimate definition of
      effectiveness and efficiency," and there is an increasing emphasis on identifying
      and measuring the results of interventions and practice. This new department will
      focus on issues surrounding patient outcomes such as definitions, measurement,
      sources of data, nurse-sensitive versus multidisciplinary outcomes, and
      determining the evidence on which to base practice. The goal of the department is
      to stimulate questions and encourage discussion that will contribute to the
      necessary knowledge for defining, measuring, and ultimately improving
      cardiovascular patient outcomes.

PMID- 9645623
TI  - Factors influencing selected lengths of ICU stay for coronary artery bypass
      patients.
AB  - This study examines factors influencing the length of intensive care unit stay
      for patients after coronary artery bypass surgery. Profiles of patients with
      selected lengths of ICU stay were identified for Group 1 (< or =1 day) and Group
      2 (> or =2 days). Medical records of 175 patients who had undergone this
      procedure at an urban teaching hospital were reviewed. Patients who had a 1-day
      ICU length of stay were younger (mean=62.39, SD=10.88) and had comorbidities such
      as hypertension. Those patients with an ICU length of stay 2 days or longer were
      older (mean=68.18, SD=11.84) and had preoperative comorbidities such as
      congestive heart failure, chronic obstructive pulmonary disease, ejection
      fraction <50%, and need for an intra-aortic balloon pump. Atrial dysrhythmias,
      low cardiac output syndrome, renal insufficiency, and respiratory insufficiency
      were the postoperative complications associated with a prolonged ICU length of
      stay. Knowledge of the factors influencing selected lengths of ICU stay will
      enable nurses to choose patients for critical pathways and to anticipate
      postoperative problems in high-risk patients.

PMID- 9645624
TI  - Patient perceived health status, hospital length of stay, and readmission after
      coronary artery bypass surgery.
AB  - This study evaluates the effect of length of stay and baseline health status on
      health status and readmission rates 3 months after coronary artery bypass graft
      surgery. Baseline health status showed a trend toward worse scores for patients
      who were readmitted. Readmitted patients had longer lengths of stay, and worse 3
      month health status scores, and women and patients with heart failure had higher
      readmission rates. It may be possible to identify patients at risk for
      readmission using clinical variables, length of stay, and health status. If a
      predictive model can be developed, then interventions can be developed and tested
      to decrease the rate of unplanned readmissions.

PMID- 9645625
TI  - Patient education for discharge after coronary bypass surgery in the 1990s: are
      patients adequately prepared?
AB  - Short hospitalizations for patients undergoing coronary artery bypass grafting
      (CABG) require continuous nursing evaluation of patients' discharge education.
      Six institutions collaborated in surveying 300 postoperative patients with CABG
      to identify learning priorities and patients' perceptions of the effectiveness of
      discharge education. Data analysis from the self-administered questionnaire
      demonstrated consistent patient priorities across institutions. Differences in
      teaching methods and content did not affect perceived preparedness or importance
      scores. Regional experience demonstrates that variable teaching efforts meet
      patients' priorities and provide high overall patient preparedness for discharge.
      Patients with the shortest hospitalizations had higher preparedness scores.

PMID- 9645626
TI  - Complementary therapy and cardiac surgery.
AB  - Mind-body techniques and complementary care may assist people who are undergoing
      surgery and those recovering from cardiac surgery to cope with the event, the
      process of recovery, and accompanying lifestyle changes. These approaches can
      provide cardiac patients with nonpharmacologic tools that may prevent further
      coronary artery disease and the development of dysrhythmias. The Complementary
      Care Center at Columbia-Presbyterian Medical Center was developed to clinically
      apply and research the use of nonallopathic, complementary modalities with
      patients receiving care at the medical center, including those undergoing cardiac
      surgery.

PMID- 9645627
TI  - Cellular sequences in stealth viruses.
AB  - Cloned DNA obtained from the culture of an African green monkey simian
      cytomegalovirus-derived stealth virus contains multiple discrete regions of
      significant sequence homology (p values ranging from 4 x 10(-3) to 1 x 10(-20))
      to portions of known human cellular genes. The stealth virus was cultured from a
      patient with chronic fatigue syndrome (CFS). Earlier studies had revealed
      considerable sequence heterogeneity within DNA fragments isolated from virus
      infected cells. A set of polymerase chain reaction (PCR) primers generated
      different PCR products when tested on stealth virus cultures from 4 patients with
      CFS. Several of the PCR products also contain regions of significant partial
      homology to distinct cellular sequences, including sequences repetitively
      expressed throughout the cellular genome. Stealth viruses may play an important
      role in the origins and in the genetic diversity of both viral and cellular
      sequences.

PMID- 9645628
TI  - Fluorescent in situ hybridization detection of HER-2/neu gene amplification in
      rhabdomyosarcoma.
AB  - Embryonal rhabdomyosarcoma is the most common malignant soft-tissue tumor in
      childhood, comprising 45-50% of childhood sarcomas. Cytogenetic studies of this
      tumor are rare. In view of the paucity of cytogenetic data on this cancer and
      based on the finding of HER-2/neu gene amplification in a number of cancers that
      was detected mostly using the traditional technique of immunohistochemistry, we
      decided to conduct a pilot study to investigate whether HER-2/neu gene
      amplification in this tumor can be detected using the newer technique of
      fluorescent in situ hybridization (FISH). Archival tissues of rhabdomyosarcoma
      were retrieved and FISH using an HER-2/neu probe was undertaken on formalin-fixed
      paraffin-embedded tissue sections using a protocol optimized for our laboratory
      at Rhode Island Hospital. Out of 9 cases of rhabdomyosarcoma studied to date, 1
      case clearly showed HER-2/neu gene amplification. Thus, FISH is a sensitive
      technique suitable for the detection of oncogene amplification and the
      delineation of tumor heterogeneity in this tumor. Future experiments utilizing
      additional specimens from our centers as well as from other laboratories will be
      needed to extend the finding in the present pilot study.

PMID- 9645629
TI  - Chemokine expression in endothelial cells and monocytes is differentially
      regulated.
AB  - Endothelial cells play a critical role in the recruitment of immune cells due to
      their position at the interface between circulating cells and the inflamed
      tissue. In this study, human umbilical vein endothelial cells (HUVECs) and human
      monocytes were used to investigate the role of various cytokines in the
      regulation of C-C and C-X-C chemokine production. We have demonstrated that IL-4
      and IL-10 negatively affect certain monocyte-derived chemokines, while not
      suppressing HUVEC-derived chemokines. The differential induction of chemokines by
      selected cytokines may help delineate the type(s) of leukocytes that are
      recruited during certain phases of an inflammatory response.

PMID- 9645630
TI  - Choline deficiency induces apoptosis and decreases the number of eosinophilic
      preneoplastic foci in the liver of OXYS rats.
AB  - Choline deficiency (CD) was previously shown to trigger apoptosis in rat
      hepatocytes in culture and in vivo. In the present study we investigated the
      effects of short-term withdrawal of choline from the diet on the expression of
      putative preneoplastic foci in OXYS rats, an inbred strain with an inherited
      overproduction of free radicals. Animals were fed a defined, choline-sufficient
      (CS, control) or choline-deficient (CD) diet for 6 weeks. Eosinophilic,
      glutathione S-transferase (pi class) (+) preneoplastic foci were found in
      histologic sections of control OXYS rat liver. CD caused a 60% decrease in the
      number of eosinophilic foci per liver section (27.0+/-6.1 vs. 10.6+/-4.6
      foci/section) compared to CS controls. Apoptotic bodies were detected in 0.18+/
      0.03% of hepatocytes in CD livers compared to 0.05+/-0.009% of hepatocytes in
      controls. Cells which exhibited an apoptotic morphology in hematoxylin and eosin
      stained sections were TUNEL-positive, confirming the induction of apoptosis. Also
      in CD animals compared to controls, there was an increased expression of p27Kip1
      protein, and a reduction in PCNA nuclear labeling and the number of mitotic
      figures, consistent with an inhibition of cell proliferation in the livers of CD
      animals. This study shows that the liver of OXYS rats with an inherited
      overgeneration of free radicals retains sensitivity to CD, and that this p53
      independent trigger of apoptosis can decrease the number of eosinophilic foci in
      the livers of these animals.

PMID- 9645631
TI  - Comparison of a pneumococcal common protein (PsaA) antibody ELISA and a PsaA
      immune complex ELISA for detection of pneumococcal serum antibody.
AB  - We examined and compared results from three assays, an enzyme-linked
      immunosorbent assay (ELISA) and two immune complex ELISAs for analysis of the
      serum antibody response to a native pneumococcal 37-kD common cell-wall protein
      by using acute- and convalescent-phase sera from 56 patients with community
      acquired pneumonia. The sensitivities of the ELISA, the undissociated and
      dissociated immune complex assays were 85% (23 of 27), 78% (21 of 27) and 67% (18
      of 27), respectively. To determine specificity, paired sera from patients with
      pneumonia of other bacterial etiologies were tested. The specificities were 83,
      83 and 72% for the ELISA, undissociated immune complex, and dissociated immune
      complex, respectively. Based on this study, the sensitivities of the three assays
      were not statistically different. These tests could be used retrospectively to
      confirm invasive pneumococcal disease.

PMID- 9645632
TI  - Epinephrine augments specific T-cell responses to antigen in C57BL/6 (H-2b) weak
      responder mice by a CD8+ lymphocyte-dependent mechanism.
AB  - Stress has been implicated as a factor in the pathogenesis of autoimmune
      disorders. In order to determine the effect of adrenergic stress on immune
      responses in vivo, C57BL/6 (B6; H-2b) mice, which respond weakly to hen-egg
      lysozyme (HEL), were immunized on day 0 with HEL (50-200 microg s.q.) and
      subsequently injected with epinephrine (EPI; 0.1-0.5 mg/kg s.q.) daily for up to
      10 days. Controls included A/J mice (H-2k) which respond strongly to HEL. In some
      experiments, B6 mice were depleted of CD4+ or CD8+ lymphocytes by monoclonal
      antibody treatment in vivo, prior to immunization with HEL, and injection with
      EPI. On day 10, single cell suspensions of draining lymph nodes (LN) and spleen
      were examined for immune phenotype, proliferative responses to HEL, and
      lymphokine production. Minimal specific proliferative responses were detected in
      B6 mice compared to A/J mice. However, lymphocyte proliferation increased in HEL
      immunized EPI-treated B6 mice but not in the A/J mice. IL-2-mediated
      proliferation and IL-2 secretion were both increased in the HEL-immunized EPI
      treated B6 mice. The depletion of CD8+ but not CD4+ lymphocytes in vivo abrogated
      the effects of EPI, whereas adoptive transfer of naive CD8+ splenocytes to the
      CD8-depleted mice restored specific responses in the HEL-immunized EPI-treated
      animals. We conclude that EPI augments antigen-specific T-cell responses to HEL
      in B6 mice by a CD8+ T-cell-dependent mechanism.

PMID- 9645633
TI  - Comparison of alopecia areata in human and nonhuman mammalian species.
AB  - Alopecia areata (AA) is a nonscarring form of inflammatory hair loss in humans.
      AA-like hair loss has also been observed in other species. In recent years the
      Dundee experimental bald rat and the C3H/HeJ mouse have been put forward as
      models for human AA. AA in all species presents with a wide range of clinical
      features from focal, locally extensive, diffuse hair loss, to near universal
      alopecia. Histologically, all species have dystrophic anagen stage hair follicles
      associated with a peri- and intrafollicular inflammatory cell infiltrate.
      Autoantibodies directed against anagen stage hair follicle structures are a
      consistent finding. Observations on AA pathogenesis suggest nonhuman species can
      provide excellent models for the human disease. Ultimately, animal models will be
      used to determine the genetic basis of AA, potential endogenous and/or
      environmental trigger(s), mechanism(s) of disease initiation and progression, and
      allow rapid evaluation of new and improved disease treatments.

PMID- 9645634
TI  - Erythrasma treated with single-dose clarithromycin.

PMID- 9645635
TI  - Topical metronidazole maintains remissions of rosacea.
AB  - BACKGROUND: Rosacea is a chronic skin disease that requires long-term therapy.
      Oral antibiotics and topical metronidazole successfully treat rosacea. Because
      long-term use of systemic antibiotics carries risks for systemic complications
      and adverse reactions, topical treatments are preferred. OBJECTIVE: To determine
      if the use of topical metronidazole gel (Metrogel) could prevent relapse of
      moderate to severe rosacea. DESIGN: A combination of oral tetracycline and
      topical metronidazole gel was used to treat 113 subjects with rosacea (open
      portion of the study). Successfully treated subjects (n = 88) entered a
      randomized, double-blind, placebo-controlled study applying either 0.75% topical
      metronidazole gel (active agent) or topical metronidazole vehicle gel (placebo)
      twice daily (blinded portion of the study). SETTING: Subjects were enrolled at 6
      separate sites in large cities at sites associated with major medical centers.
      SUBJECTS: One hundred thirteen subjects with at least 6 inflammatory papules and
      pustules, moderate to severe facial erythema and telangiectasia entered the open
      phase of the study. Eighty-eight subjects responded to treatment with systemic
      tetracycline and topical metronidazole gel as measured by at least a 70%
      reduction in the number of inflammatory lesions. These subjects were randomized
      to receive 1 of 2 treatments: either 0.75% metronidazole gel or placebo gel.
      INTERVENTIONS: Subjects were evaluated monthly for up to 6 months to determine
      relapse rates. MAIN OUTCOME MEASURES: Inflammatory papules and pustules were
      counted at each visit. Relapse was determined by the appearance of a clinically
      significant increase in the number of papules and pustules. Prominence of
      telangiectases and dryness (roughness and scaling) were also observed. RESULTS:
      In the open phase, treatment with tetracycline and metronidazole gel eliminated
      all papules and pustules in 67 subjects (59%). The faces of 104 subjects (92%)
      displayed fewer papules and pustules after treatment, and 82 subjects (73%)
      exhibited less erythema. In the randomized double-blind phase, the use of topical
      metronidazole significantly prolonged the disease-free interval and minimized
      recurrence compared with subjects treated with the vehicle. Eighteen (42%) of 43
      subjects applying the vehicle experienced relapse, compared with 9 (23%) of 39
      subjects applying metronidazole gel (P<.05). The metronidazole group had fewer
      papules and/or pustules after 6 months of treatment (P<.01). Relapse of erythema
      also occurred less often in subjects treated with metronidazole (74% vs 55%).
      CONCLUSION: In a majority of subjects studied, continued treatment with
      metronidazole gel alone maintains remission of moderate to severe rosacea induced
      by treatment with oral tetracycline and topical metronidazole gel.

PMID- 9645636
TI  - Intra-incisional prophylactic antibiotics for dermatologic surgery.
AB  - OBJECTIVE: To determine the efficacy of intra-incisional antibiotics in
      decreasing the risk of wound infections in cutaneous surgery. DESIGN:
      Prospective, blinded, randomized, placebo-controlled trial conducted during an 8
      month period. SETTING: A private practice Mohs micrographic surgery referral
      center. PATIENTS: Seven hundred ninety consecutive patients referred for Mohs
      surgery or other dermatologic surgery were randomized to receive anesthesia
      either with study compound or placebo. The 2 groups were equivalent with respect
      to age and sex distribution and the lesions treated were similar in character. No
      patients were withdrawn for adverse effects. INTERVENTIONS: Patients received
      local anesthesia before surgery with either buffered lidocaine hydrochloride or a
      solution consisting of nafcillin sodium in buffered lidocaine. MAIN OUTCOME
      MEASURES: All surgical wounds were evaluated in a blinded fashion at the time of
      suture removal (5-7 days) and scored according to a standardized assessment chart
      based on erythema, edema, and the presence of purulent discharge. RESULTS: Seven
      hundred ninety consecutive patients with 908 surgical wounds were enrolled in
      this study. A total of 12 wound infections were recorded. Eleven (2.5%) of these
      occurred in the control group, while only 1 (0.2%) occurred in the nafcillin
      group. This difference was highly significant (P = .003). Observers were blinded
      to patient groupings particularly for surgical wound scoring. CONCLUSIONS: This
      study offers strong supporting data for the use of a single intra-incisional dose
      of an antibiotic administered immediately before dermatologic surgery. The use of
      nafcillin and buffered lidocaine solution is inexpensive, safe, convenient, and
      effective.

PMID- 9645637
TI  - Human herpesvirus 8 in Italian HIV-seronegative patients with Kaposi sarcoma.
AB  - OBJECTIVE: To evaluate the prevalence of human herpesvirus 8 (HHV-8) DNA
      detection in a large series of human immunodeficiency virus-seronegative patients
      with and without Kaposi sarcoma (KS) from the central and southern regions of
      Italy where classic KS is prevalent. DESIGN: Samples of lesional, peripheral
      unaffected, and distant normal skin and peripheral blood mononuclear cells
      (PBMCs) from 33 patients with KS and PBMCs from 42 control subjects were analyzed
      using single and nested polymerase chain reaction techniques for the presence of
      HHV-8 DNA. PATIENTS: A total of 33 patients with KS not related to acquired
      immunodeficiency syndrome (26 patients with classic KS and 7 patients with
      iatrogenic KS) were studied. Furthermore, 2 control groups were enrolled. The
      first group consisted of 13 healthy volunteers, the second of 29 patients
      affected by different dermatological diseases. RESULTS: Human herpesvirus 8
      sequences were found in 100% of lesional and perilesional specimens, in 33% of
      the distant normal skin samples, and in 69.6% of the PBMCs from patients with KS.
      A possible correlation between HHV-8 DNA in PBMCs and the clinical stage of the
      disease was observed. Moreover, the prevalence of viral DNA in PBMCs from the
      total control group was 23.8%. No viral DNA was detected in tissue biopsy
      specimens taken from the control group. CONCLUSIONS: Our data suggest that HHV-8
      could be a widespread virus, at least in Mediterranean regions where KS is more
      prevalent, such as southern and central Italy. As with other herpesviruses, it
      may be present lifelong in latent form somewhere in the body and may contribute
      to the pathogenesis of KS when other predisposing conditions are present.

PMID- 9645638
TI  - Prevalence of human herpesvirus 8 infection measured by antibodies to a latent
      nuclear antigen in patients with various dermatologic diseases.
AB  - BACKGROUND: Human herpesvirus 8 (HHV-8) has been detected in all epidemiological
      forms of Kaposi sarcoma (KS). The role of HHV-8 in dermatologic diseases other
      than KS is controversial. Some studies based on polymerase chain reaction
      findings suggest an association between HHV-8 and epithelial tumors of the skin,
      lymphoproliferative disorders, or pemphigus. OBJECTIVE: To assess the prevalence
      of antibodies against a latent nuclear antigen of HHV-8 in patients with various
      dermatologic diseases. DESIGN: An indirect immunofluorescence assay was used to
      search for HHV-8 antibodies. SETTING: Ambulatory or hospitalized patients from a
      university hospital associated with a research laboratory. PATIENTS: Eighty-three
      patients with various non-KS dermatologic diseases and 16 patients with KS who
      were seronegative for the human immunodeficiency virus. Controls were 100 healthy
      subjects living in the same area. RESULTS: Antibodies to HHV-8 were found in 100%
      (16/16) of the patients with KS and 3.6% (3/83) of the patients with non-KS
      dermatologic diseases: 1 patient with pemphigus vulgaris, 1 with discoid lupus
      erythematosus, and 1 with bullous pemphigoid. The prevalence of antibodies to HHV
      8 in controls was 2% (2/100) and was not significantly different than the
      prevalence in patients with dermatologic diseases other than KS (P =.28).
      CONCLUSIONS: Our serologic study confirms the higher prevalence of HHV-8
      antibodies in patients with KS and demonstrates that contrary to other human
      herpesviruses, HHV-8 is not a ubiquitous virus in France. We could not determine
      any causal association between HHV-8 and pemphigus or lymphoproliferative
      disorders of the skin.

PMID- 9645639
TI  - Immunoapheresis in paraneoplastic pemphigus.
AB  - BACKGROUND: Paraneoplastic pemphigus was first described in 1990 in 5 patients
      with extensive mucocutaneous erosions, a distinct set of autoantibodies, and
      underlying neoplasia. Since then, patients described have been middle-aged, have
      suffered from prognostically unfavorable malignant neoplasms, and have responded
      poorly to immunosuppressive agents. OBSERVATION: A 16-year-old boy was examined
      with extensive oral erosions, halitosis that interfered with his quality of life,
      and rapid weight loss. The suspected clinical diagnosis of paraneoplastic
      pemphigus was confirmed by histopathological, immunofluorescence, and biochemical
      (eg, immunoblotting and immunoprecipitation) findings as well as by the
      demonstration of an inflammatory myofibroblastic tumor of the left
      retroclavicular region. Despite administration of corticosteroids, followed by
      excision of the neoplasm, clinical symptoms improved only slightly, and
      autoantibody titers decreased only marginally. We therefore initiated an
      immunoapheresis regimen with the use of sheep anti-human-IgG bead-formed agarose
      gel (Sepharose; Pharmacia Biotech Comp, Vienna, Austria), which led to the
      disappearance of circulating autoantibodies and the patient's recovery.
      CONCLUSION: Immunoapheresis may represent a novel therapeutic option for patients
      with paraneoplastic pemphigus who show little improvement after curative
      treatment of their neoplasms.

PMID- 9645640
TI  - Congenital melanocytic nevi with placental infiltration by melanocytes: a benign
      condition that mimics metastatic melanoma.
AB  - BACKGROUND: Placental metastases from cutaneous malignant melanoma from both the
      mother and the fetus have been reported. The finding of benign-appearing
      melanocytes in the placenta in association with congenital melanocytic nevi (CMN)
      is more exceptional, with only 6 reports in the literature. Clinically, the
      finding of melanocytes in the placenta in this setting can be alarming and might
      erroneously lead to the diagnosis of metastatic melanoma. OBSERVATIONS: Herein,
      we describe 3 additional patients with CMN with placental infiltration by
      melanocytes with a benign phenotype. In the results of immunoperoxidase stains,
      the melanocytic cells were positive for S-100 protein and HMB-45 in the 2 lesions
      available for study. Staining of placental vessels with Ulex europaeus agglutinin
      I (Vector Laboratories, Burlingame, Calif) failed to show intravascular
      melanocytes in the 1 lesion available for study. We report for the first time DNA
      diploidy in 2 lesions available for study, which were analyzed by DNA image
      cytometry. We describe the first patient with a relatively small, nongiant CMN.
      CONCLUSIONS: We support the notion of the aberrant migration of melanocytes from
      the neural crest during fetal development as the most likely explanation of this
      phenomenon and note the similarity to the association of CMN and leptomeningeal
      melanocytosis. However, the precise histogenesis of this process remains
      uncertain. Most importantly, our data provide further evidence for the benign
      nature of this condition. Awareness of this entity is of vital importance in
      avoiding overdiagnosis of melanoma in this clinical setting.

PMID- 9645641
TI  - Familial segregation of hemangiomas and vascular malformations as an autosomal
      dominant trait.
AB  - BACKGROUND: The pathogenesis of infantile hemangiomas is not yet understood.
      Growth factors and hormonal and mechanical influences have been thought to affect
      the focal abnormal growth of endothelial cells in these lesions. However, these
      influences may represent secondary responses to an underlying primary molecular
      event leading to the development of hemangiomas. OBSERVATIONS: We report the rare
      familial occurrence of hemangiomas and/or vascular malformations in 6 kindreds,
      suggesting autosomal dominant inheritance. In these families, multiple
      generations (2-4) were affected by hemangiomas or vascular malformations. In
      contrast to the generally accepted female-male ratio of 3:1 to 4:1 associated
      with sporadic hemangiomas, the families with hemangiomas in our study
      demonstrated a 2:1 ratio. Additionally, vascular malformations and hemangiomas
      were present in different members of the same family. The vascular lesions
      appeared to be transmitted in an autosomal dominant fashion with moderate to high
      penetrance. CONCLUSIONS: We have identified 6 families demonstrating autosomal
      dominant segregation of childhood hemangiomas. Additionally, family members with
      vascular malformations were identified in these kindreds. Physicians caring for
      children with hemangiomas and vascular malformations should include in their
      medical histories inquiries about vascular lesions in other family members, even
      when obvious lesions are not present in the parents. The identification of the
      mutation(s) underlying vascular lesions will provide insight into the
      pathogenesis of these familial hemangiomas and, potentially, common sporadic
      hemangiomas. In addition, such research would shed light on the regulation of
      angiogenic processes during development.

PMID- 9645642
TI  - Interactive mechanisms for teaching dermatology to medical students.
AB  - OBJECTIVES: To develop interactive teaching mechanisms for an "Introduction to
      Dermatology" course for medical students and to compare the effectiveness and
      impact of these mechanisms on learning. DESIGN: Survey and before-after trial.
      SETTING: Medical school. PARTICIPANTS: Second-year medical students
      (approximately 200 per year). MAIN OUTCOME MEASURES: The teaching mechanisms were
      evaluated through responses to questionnaire-based course evaluations (survey).
      The impact of the CD-ROM program was assessed by performance in Kodachrome slide
      based multiple choice examinations (before-after trial). RESULTS: Overall the
      course was highly rated and among its components, the live-patient sessions, the
      CD-ROM program, and the poster exhibit were rated most effective. There was no
      difference in the examination performance of students who took the course before
      and after inclusion of the CD-ROM program. High-scoring students attended a
      significantly greater number of lectures in comparison with low-scoring students.
      CONCLUSIONS: The 3 teaching mechanisms judged by students to be most effective
      were also the most visual and interactive, suggesting that these attributes are
      critical to learning dermatology. On the other hand, addition of the CD-ROM
      program failed to produce differential improvement in short-term cognitive
      skills.

PMID- 9645643
TI  - What do medical students need and what do they want?

PMID- 9645644
TI  - Human herpesvirus 8 as the infectious cause of Kaposi sarcoma: evidence and
      involvement of cofactors.

PMID- 9645645
TI  - Evolving knowledge of hemangiomas and vascular malformations: beyond strawberries
      and port wine.

PMID- 9645646
TI  - Chronic unilateral leg inflammation in a young man.

PMID- 9645647
TI  - Multiple chronic lesions with peripheral scale.

PMID- 9645648
TI  - Hypopigmentation of the extremities.

PMID- 9645649
TI  - Multiple asymptomatic papules in the popliteal fossa.

PMID- 9645650
TI  - Human herpesvirus 8 DNA sequences in pemphigus: the role of the virus in
      oncogenic and autoimmune manifestations.

PMID- 9645651
TI  - Therapeutic options for superficial basal cell carcinoma: the role of radiation
      therapy.

PMID- 9645652
TI  - Conservative clinical diagnoses in seborrheic keratosis.

PMID- 9645653
TI  - Further evidence that syringolymphoid hyperplasia with alopecia is a cutaneous T
      cell lymphoma.

PMID- 9645654
TI  - Hypopigmented common blue nevi.

PMID- 9645655
TI  - Oral mucosa is frequently affected in patients with dermatitis herpetiformis.

PMID- 9645656
TI  - Human herpesvirus 6 infection in patients with exanthema after allogeneic bone
      marrow transplantation.

PMID- 9645657
TI  - Clustered angiofibromas on the ear of a patient with neurofibromatosis type 2.

PMID- 9645658
TI  - Public education on-line.

PMID- 9645659
TI  - Gamma ray imaging systems.

PMID- 9645660
TI  - On the discrepancy between epidemiologic studies in individuals of lung cancer
      and residential radon and Cohen's ecologic regression.
AB  - There is still substantial confusion in the radiation effects community about the
      inherent limitations of ecologic analysis. As a result, inordinate attention has
      been given to the discrepant results of Cohen, in which a negative estimate is
      observed for the regression of county mortality rates for lung cancer on
      estimated county radon levels. This paper demonstrates that Cohen's ecologic
      analysis cannot produce valid inference on the exposure-response relationship for
      individuals unless lung cancer risk factors (smoking, age, occupation, etc.) for
      individuals are statistically uncorrelated with indoor radon level within
      counties or unless risk effects for radon and other factors are additive. Both of
      these assumptions are contradicted in the literature. Thus, contrary to common
      assumption, when a linear no-threshold model is the true model for radon risk for
      individuals, higher average radon concentration for a county does not necessarily
      imply a higher lung cancer rate for the county. In addition, valid inference from
      county-level ecologic analysis and the elimination of the ecologic bias cannot be
      achieved with the addition of county-wide summary variables (including
      "stratification" variables) to the regression equation. Using hypothetical data
      for smoking and radon and assuming a true positive association for radon and lung
      cancer for individuals, the analysis demonstrates that a negative county-level
      ecologic regression can be induced when correlation coefficients for smoking and
      radon within county are in the range -0.05 to 0.05. Since adverse effects for
      radon at low exposures are supported by analysis of miner data (all data and data
      restricted only to low cumulative exposures), a meta-analysis of indoor radon
      studies, and molecular and cellular studies, and since ecologic regressions are
      burdened by severe limitations, the negative results from Cohen's analysis are
      most likely due to bias and should be rejected.

PMID- 9645661
TI  - Residential 222Rn exposure and lung cancer: testing the linear no-threshold
      theory with ecologic data.
AB  - In most rigorous epidemiologic studies, such as case-control and cohort studies,
      the basic unit of analysis is the individual. Each individual is classified in
      terms of exposure and disease status. However, in ecologic epidemiologic studies,
      the unit of analysis is some aggregate group of individuals. Summary measures of
      exposure and disease frequency are obtained for each aggregate, and the analyses
      focus on determining whether or not the aggregates with high levels of exposure
      also display high disease rates. The ecologic study design has major limitations,
      including ecologic confounding and cross level bias. Cohen has attempted to
      circumvent these limitations by invoking the linear no-threshold theory of
      radiation carcinogenesis to derive aggregate "exposures" from individual-level
      associations. He asserts that, "while an ecologic study cannot determine whether
      radon causes lung cancer, it can test the validity of a linear-no threshold
      relationship between them." Cohen compares his testing of the linear no-threshold
      relationship between radon exposure and lung cancer to the practice of estimating
      the number of deaths from the person-rem collective dose, dividing the person-rem
      by the number of individuals in the population to derive the individual average
      dose, and then determining individual average risk by dividing the number of
      deaths by the number of individuals in the population. We show that Cohen's
      erroneous assumptions concerning occupancy rates and smoking effects result in
      the use of the wrong model to test the linear no-threshold theory. Because of
      these assumptions, the ecologic confounding and cross level bias associated with
      Cohen's model invalidate his findings. Furthermore, when more recent Iowa county
      lung cancer incidence rates are regressed on Cohen's mean radon levels, the
      reported large negative associations between radon exposure and lung cancer are
      no longer obtained.

PMID- 9645662
TI  - Response to Lubin's proposed explanations of our discrepancy.
AB  - Lubin's proposal that a correlation between radon and smoking among individuals
      might explain the very large discrepancy between our data on U.S. counties and
      the prediction of linear no-threshold theory of radiation induced cancer is
      tested. It is shown that even correlations far beyond the limits of plausibility
      cannot explain an appreciable part of our discrepancy. On the other hand, Lubin
      is commended for proposing a definite potential explanation for our discrepancy
      that can be quantitatively tested for applicability to our analysis, and further
      such proposals are strongly invited. All other explanations of our discrepancy
      and all other reasons for not accepting our conclusions that are proposed in the
      Lubin paper are shown not to be applicable. The role of plausibility in
      epidemiological studies is discussed and shown to be all-important.

PMID- 9645663
TI  - Response to criticisms of Smith et al.
AB  - The various criticisms of our test of the linear no-threshold theory of radiation
      carcinogenesis in the paper by Smith et al. are considered and shown to be
      invalid. It is shown that there is no significant difference between the BEIR IV
      formula and the formula we use, that the uncertainties in effective average radon
      exposures in U.S. counties due to the issues they raise are not very large and
      that even if they were implausibly large, the results of our study would not be
      much affected. I review the seven essentially independent methods we used to
      estimate smoking prevalence, all of which give the same results but most of
      which, including the most important, were ignored by Smith et al.; explaining our
      results by uncertainties in smoking data would require correlations between radon
      and smoking that are grossly implausible. Our use of measurements of radon,
      smoking, and lung cancer rates from different time periods is justified, and it
      is shown that if more recent lung cancer rates are used, the results are not
      changed. Problems in comparing Iowa data with our study are discussed. It is
      shown that many of their criticisms of our study are more applicable to the case
      control and cohort studies that they endorse. Many of their conclusions are
      presented without valid supporting evidence. A simple procedure is suggested that
      can easily settle any questions about the validity of our study; with this
      procedure, I offer to show that any other published ecological study might give
      invalid results. The point here is that our study is very different from all
      other published ecological studies.

PMID- 9645664
TI  - 237Np: oxidation state in vivo and chelation by multidentate catecholate and
      hydroxypyridinonate ligands.
AB  - Chemically, 237Np(V) is as toxic as U(VI), and radiologically, about as toxic as
      239Pu. Depending on redox conditions in vivo, 237Np exists as weakly complexing
      Np(V) (NpO2+) or as Np(IV), which forms complexes as stable as those of Pu(IV).
      Ten multidentate catecholate (CAM) and hydroxypyridinonate (HOPO) ligands with
      great affinity for Pu(IV) were compared with CaNa3-DTPA for in vivo chelation of
      237Np. Mice were injected intravenously with 237NpO2Cl: those in a kinetic study
      were killed 1 to 2880 min; in ligand studies, fed mice were injected
      intraperitoneally with a ligand 5, 60, or 1440 min after 237Np(V) (molar ratio
      5.6 to 73), mice fasted for 16 h were gastrically intubated with a ligand 3 min
      after 237Np(V) (molar ratio 5.6 to 274), and all were killed 24 h after ligand
      administration; tissues and excreta were radioanalyzed. Rapid plasma clearance
      and urinary excretion of 237Np(V) resemble U(VI); deposition and early retention
      in skeleton and liver resemble Pu(IV). The x-ray absorption near edge structure
      spectroscopy (XANES) spectra of femora of 237Np(V)-injected mice, compared with
      spectra of Np(V) and Np(IV) from reference solids, showed predominantly Np(IV).
      Significant in vivo 237Np chelation was obtained with all of the HOPO and CAM
      ligands injected at molar ratio 22; the HOPO ligands reduced 237Np in skeleton,
      liver, and other soft tissue, on average, to 72, 25, and 25% of control,
      respectively, while CaNa3-DTPA was ineffective. Two HOPO ligands injected 60 min
      after 237Np (molar ratio 5.6) significantly reduced body and liver 237Np, and
      three HOPO ligands given orally (molar ratio > or = 73) significantly reduced
      body and liver 237Np, compared with controls. Combined with earlier work, these
      results indicate that: the dominant neptunium species circulating and excreted in
      urine is Np(V), while that in bone and liver deposits is Np(IV); Np(V) must be
      reduced to Np(IV) before it can be stably chelated; efficient decorporation of
      neptunium requires multidentate ligands that form exceptionally stable
      actinide(IV) chelates and facilitate Np(V) reduction.

PMID- 9645665
TI  - Radiofrequency electromagnetic fields (300 Hz-300 GHz) summary of an advisory
      report. Health Council of The Netherlands: Radiofrequency Radiation Committee.
AB  - In a report prepared by an expert committee of the Health Council of the
      Netherlands, health-based exposure limits for radiofrequency electromagnetic
      fields in the frequency range 300 Hz-300 GHz are given. The present paper is a
      summary of the recommendations in the report and of their rationales.

PMID- 9645666
TI  - Tritium concentrations inside the homes of occupationally exposed workers:
      dosimetric implications.
AB  - The average tritiated water concentration in the indoor air of the occupationally
      exposed worker's residence (55 Bq m(-3), range 53-59 Bq m(-3)) was higher than
      the indoor air of control residences (0.7 Bq m(-3), range 0.4-0.8 Bq m(-3)). The
      worker had an average concentration of tritium-in-urine of 30 kBq L(-1) from
      chronic intakes of occupational levels of tritiated water. Higher residential
      concentrations of tritiated water vapor were due to tritium transferred by the
      worker. Urine samples from an adult co-occupant were collected and had tritiated
      water concentrations between 89 and 345 Bq L(-1). These concentrations were
      higher than for individuals (range, 6-32 Bq L(-1)) living in other residences
      having similar outdoor and indoor concentrations of tritiated water in air. The
      range of measured tritiated water in urine was in agreement with the prediction
      of biokinetic models for tritium intakes as recommended by the International
      Commission on Radiological Protection Publication 56. The tritiated water vapor
      in the indoor air of the exposed worker's residence contributed about 96% of the
      daily tritium intakes. The annual average tritium dose to the family member (7
      microSv) was well below the International Commission on Radiological Protection
      Publication 60 recommended annual dose limit (1 mSv) for members of the public.
      We conclude that, for a few members of the public living near a heavy-water
      research reactor facility, daily intakes of tritium will relate to tritiated
      water dispersed by the exposed worker, as well as to tritium transported by the
      atmosphere from the reactor site.

PMID- 9645667
TI  - Comparative studies of indoor radon concentration levels in Jordan using CR-39
      based bag and cup dosimeters.
AB  - Indoor radon concentration levels have been measured in 9 major cities of Jordan
      using CR(-3)9 detectors placed in punched polyethylene bags to measure both radon
      and thoron, and in cups to measure radon only. The average value of indoor radon
      and thoron concentration levels measured with bag dosimeters vary from 32 to 107
      Bq m(-3) and the indoor radon concentration levels measured with cup dosimeters
      vary from 27 to 88 Bq m(-3). The indoor radon concentration levels in Irbid and
      Zaraka are comparable to the world average of 27 Bq m(-3). In Ajloun, Jerash,
      Salt, Tafilah and Amman, the indoor radon levels are greater than the world
      average by a factor of up to 2, and in Madaba and Karak these levels are greater
      than the world average by a factor of more than 3. The large variation in the
      measured radon levels may be attributed to the large variation in the 226Ra
      activity in the soil of the region.

PMID- 9645668
TI  - Estimation of environmental gamma background radiation levels in Pakistan.
AB  - For the purpose of preparing an environmental gamma radiation map of Pakistan,
      the geological materials exposed in the country were divided into eight different
      classes. Using average 238U, 232Th, and 40K content of these materials, total
      absorbed dose rate in these rocks was calculated. The dose rate in the
      environment ranged from 1 nGy h(-1) to 97 nGy h(-1) with a mean value of 59 nGy
      h(-1). These data are presented as a dose rate map of Pakistan. This map provides
      a usable regional picture of environmental gamma background radiation levels
      excluding cosmic radiation in Pakistan.

PMID- 9645669
TI  - Model for estimating population impacts averted through the remediation of
      contaminated soil.
AB  - This is the second in a series of papers that discuss methodologies being
      developed and employed by the U.S. Environmental Protection Agency in support of
      its decisions on cleanup levels for radioactively contaminated sites that are to
      be remediated and released for public use. It describes a model, CU-POP, designed
      by the U.S. Environmental Protection Agency to obtain estimates of the potential
      collective radiological health impacts over specific periods of time (100, 1,000
      and 10,000 y following cleanup), both on and off site, due to residual
      radioactive materials in on-site soil. Collective doses and risks are linear in
      population density for the direct exposure, dust and indoor radon inhalation, and
      soil ingestion pathways; it is assumed that specific fractions of all food grown
      and all groundwater pumped at a site are consumed by on- and off-site
      populations. The model was developed for application to a set of hypothetical
      "reference" sites; its testing on a simple generic site is discussed briefly
      here.

PMID- 9645670
TI  - Effects of intake function shape on internal dose estimations.
AB  - The estimated values of time-integrated dose equivalent are different if one
      assumes continuous intake, such as is the case for longer-term environmental
      exposures, instead of instantaneous intake, which is the assumption made for most
      standardized computational procedures. This paper presents the solutions of the
      first order kinetic equations for the ICRP 30 models of the respiratory system
      (RS) and the gastrointestinal tract (GI) for continuous activity intake. These
      solutions are applied to compute the cumulated number of disintegrations for
      different intake and integration times in order to show the effects of the
      assumptions of instantaneous intake vs. continuous intake on dose. For pulmonary
      clearance class D compounds instantaneous and continuous intake functions result
      in dose estimations agreeing to within 10% (when normalized to total intake) for
      integration times larger than 8 d for both RS and GI, for the case of
      radionuclides with radiological half-lives ranging between 8 d and 10(7) y. For
      141Ce (class W) for both RS and GI the temporal intake function affects the dose
      by less than 10% for integration times greater than 280 d. In this case, the
      results for GI are less sensitive to the type of intake assumed than those for
      RS: the ratio of the number of transformations with the two intake assumptions
      has values of 0.8 or less for intake times of less than 7 d for GI and for intake
      times of less than 153 d for RS. For radionuclides such as 89Sr and 90Sr (class
      Y), the magnitude of the dose is very sensitive to the assumption made regarding
      the intake and has a strong dependence on the radionuclide half-life: for a 10%
      accuracy in dose evaluation for a continuous intake treated as instantaneous, the
      integration time must be greater than 650 d for 89Sr and 18,000 d for 90Sr. For
      all cases studied, the assumption of instantaneous intake overestimates the
      integrated dose for a continuous intake. More accurate internal dose evaluations
      may be made by consideration of the intake function shape when dose integration
      times less than approximately 10 y are of interest and non-instantaneous intakes
      are believed to have occurred.

PMID- 9645671
TI  - Long-term decrease of atmospheric test 137Cs in the soil-prairie plant-milk
      pathway in southern Chile.
AB  - The time dependency of nuclear test 137Cs in soil, prairie plants, and milk was
      observed on pastures of seven dairy farms in the 10th Region, Chile, from 1982 to
      1997, without any appreciable deposition of radioactive fallout after 1983.
      Whereas the 137Cs concentration in the soil decreased at a rate close to that of
      the radionuclide's physical decay during the whole observation period, the rate
      of decrease of the 137Cs concentration in the prairie plants and in the milk,
      having been very rapid between 1982-1990, became slower between 1991-1997. The
      effective half-lives of the concentration in plants were found to be 5.6 y and 12
      y during the first and second observation periods, respectively. Similar half
      lives of 5.5 y and 13 y were found for the concentration decline in milk during
      each period. These data clearly demonstrate a reduction in the long-term decrease
      of the 137Cs plant uptake, and consequently in the decrease of the 137Cs
      concentration in milk, resulting from a decline of 137Cs availability for prairie
      plants in the Hapludand soils over the whole 15-y observation period.

PMID- 9645672
TI  - The domino effect.

PMID- 9645673
TI  - Inhibitory actions of glucocorticoids on skeletal growth. Is local insulin-like
      growth factor I to blame?

PMID- 9645674
TI  - In situ hybridization of high density lipoprotein (scavenger, type 1) receptor
      messenger ribonucleic acid (mRNA) during folliculogenesis and luteinization:
      evidence for mRNA expression and induction by human chorionic gonadotropin
      specifically in cell types that use cholesterol for steroidogenesis.
AB  - The present studies were undertaken to examine the expression of the high density
      lipoprotein (HDL) receptor, SR-B1 messenger RNA (mRNA) in ovarian cell types
      during folliculogenesis and luteinization using in situ hybridization
      histochemistry and to examine its hormonal regulation using Northern blots. For
      the in situ study for HDL receptor mRNA localization, 21-day-old rats were
      treated with 50 IU PMSG, and ovaries were collected 0, 24, and 56 h
      postinjection. At 56 h, animals were treated with a single dose of hCG, and
      ovaries were subsequently collected at 6-, 12-, 24-, and 72-h and 5-day
      intervals. In addition, on day 4 of pseudopregnancy, a second dose of 50 IU hCG
      or saline was administered, and ovaries were collected at 12, 24, and 48 h to
      determine the induction of the expression of HDL receptor mRNA. The results of in
      situ hybridization histochemistry showed that in the immature ovary, HDL receptor
      mRNA is associated with theca interna and interstitial cells (stroma). The mRNA
      expression in these cell types increased with PMSG treatment, but no signal was
      detected in the granulosa cells. Northern blot analysis also showed a marked
      increase in mRNA content in thecal and interstitial cells during follicular
      development. During luteinization, the intensity of the signal began to appear in
      the luteinized granulosa cells. With the completion of luteinization, the signal
      in the corpus luteum tissue became more intense. Further treatment with hCG
      increased the HDL receptor mRNA content compared with that in the saline-treated
      control. These results demonstrate that the cholesterol-using cell types of the
      ovary, namely the interstitial cells, thecal cells, and fully luteinized
      granulosa cells are endowed with the HDL receptor mRNA, which provides credence
      to the functional significance of the role of HDL receptor SR-B1 in cholesterol
      transport and ovarian steroidogenesis.

PMID- 9645675
TI  - Estradiol elevates protein kinase C catalytic activity in the preoptic area of
      female rats.
AB  - Estrogen acts in the brain to regulate female reproductive physiology and
      behavior, and protein kinase C (PKC) is estrogen-regulated in many estrogen
      responsive tissues. We examined whether estrogen regulates PKC in the
      hypothalamus (HYP) and preoptic area (POA), brain regions which mediate
      estrogenic control of female reproductive function. PKC activity in tissue from
      hormone-treated and control female rats was measured, in the presence of phorbol
      ester and calcium, by quantifying 32p incorporation into a substrate peptide. PKC
      catalytic activity increased significantly in POA tissue extracts from estradiol
      treated, ovariectomized (OVX) female rats but not in HYP or cortical extracts.
      Phorbol ester potentiation of cAMP accumulation also was examined to determine
      whether the ability of PKC to potentiate adenylyl cyclase activity was affected
      by estrogen. PKC stimulation potentiated forskolin-induced cAMP accumulation to a
      greater degree in POA, but not HYP, slices from estrogen-treated OVX female rats.
      PKC enzyme levels were examined using phorbol-12,13-dibutyrate binding assays and
      immunoblots. Estrogen treatment did not change phorbol ester binding affinity or
      the density of binding sites in the POA or HYP. Immunoblots for the alpha, beta,
      and gamma PKC isoforms combined, or the gamma PKC isoform alone, did not detect
      differences between hormone-treated and control OVX female rats. Therefore,
      estrogen treatment increased PKC catalytic activity in the POA of OVX female rats
      but not in the HYP. However, the increased PKC catalytic activity was not
      correlated with detectable changes in the level of the alpha, beta, or gamma PKC
      isoforms or in the density of phorbol ester binding sites.

PMID- 9645676
TI  - Obesity and insulin resistance in human growth hormone transgenic rats.
AB  - A line of transgenic rats (heterozygotes) carrying a chimeric gene comprising a
      regulatory portion of murine whey acidic protein and a structural portion of
      human GH (hGH) genes developed severe obesity with age. To characterize
      physiological mechanisms that lead to fat accumulation, an array of parameters
      related to obesity were studied. Blood hGH levels were continuously low,
      endogenous rat GH secretion was suppressed, and the pulsatility in peripheral GH
      levels was absent. Plasma glucose, insulin, triglyceride, and FFA levels in the
      male transgenic rats significantly exceeded those in nontransgenic littermates at
      12 and 17 weeks, but not at 7 weeks, of age. All symptoms except hyperlipidemia
      were restored to normal by treatment with an antidiabetic agent,
      thiazolidinedione (troglitazone), for 1 week from 17 weeks of age. As phenotypic
      expression of obesity was already evident before aberration of physiological
      parameters, it was assumed that animals had a condition in which obesity or
      hyperlipidemia caused hyperinsulinemia. Gene expression and enzymatic activity of
      lipoprotein lipase in the adipose tissue in the transgenic rats were not
      different from those in normal rats. In contrast, the gene expression level of
      glycerol-3-phosphodehydrogenase was markedly elevated, suggesting that glycerol
      synthesis was much enhanced in the adipocytes of the transgenic rats. In an i.p.
      glucose tolerance test, the transgenic rats were not hyperglycemic at 7 weeks of
      age; however, the animal became hyperglycemic at 15-17 weeks of age. Finally,
      treatment with recombinant hGH for 1 week to produce pulsatile secretion reduced
      the size of epididymal and kidney fat pads and restored normal weight gain. These
      observations suggest that continuously low peripheral GH levels with the lack of
      pulsatile secretion resulted in obesity and noninsulin-dependent diabetes
      mellitus.

PMID- 9645677
TI  - Physiological exposure to melatonin supersensitizes the cyclic adenosine 3',5'
      monophosphate-dependent signal transduction cascade in Chinese hamster ovary
      cells expressing the human mt1 melatonin receptor.
AB  - Here, we report the effects of short exposure to melatonin on the human mt1 (h
      mt1) melatonin receptor-mediated signaling in Chinese hamster ovary (CHO) cells,
      and the consequences of an exposure that resembles the physiological pattern of
      melatonin release on cAMP-mediated signal transduction. Short exposure (10 min)
      of h mt1 melatonin receptors to melatonin (400 pM) inhibited forskolin-stimulated
      cAMP formation, cAMP-dependent protein kinase activity, and phosphorylation of
      the cAMP response element-binding protein. However, treatment of mt1-CHO cells
      with melatonin in a manner that closely mimics the in vivo activation of
      melatonin receptors (i.e. 400 pM melatonin for 8 h to mimic darkness) resulted in
      a supersensitization of the cAMP-dependent signal transduction cascade during the
      period of withdrawal (i.e. 16 h without melatonin to mimic the light cycle of a
      diurnal photoperiod). During the period of withdrawal, forskolin induced a time
      dependent (1-16 h) increase in cAMP formation (approximately 200% of control
      cells). This effect of melatonin was dependent on the presence of the h mt1
      melatonin receptor, as no potentiation of forskolin-induced cAMP formation was
      observed in CHO cells transfected only with the neomycin resistance plasmid. The
      time-dependent increase in forskolin-stimulated cAMP levels resulted in a
      potentiation of cAMP-dependent protein kinase activity 1 h after withdrawal
      (approximately 130% of control cells; P < 0.05) and in the number of cells
      containing the phosphorylated form of cAMP response element-binding protein
      (approximately 75% of cells at 1 and 16 h compared with 30% in control cells; P <
      0.05). An increase in the undissociated state (G alphabetagamma) of Gi proteins
      may underlie this phenomenon as demonstrated by the increase in pertussis toxin
      catalyzed ADP-ribosylation of G proteins (217 +/- 48% of control; P < 0.05) after
      melatonin withdrawal. This increase in the ribosylation was not due to an up
      regulation of Galpha(i) protein, as no significant change in Galpha(i) protein
      levels occurred at this time. We demonstrated that activation of the h mt1
      melatonin receptor in a manner that resembles the physiological pattern of
      melatonin exposure alters signaling, as potentiation of cAMP-mediated signal
      transduction events is observed after hormone withdrawal. The CHO cells
      expressing the human melatonin receptor may provide an in vitro cellular model in
      which to investigate the putative signaling mechanisms leading to gene regulation
      by melatonin.

PMID- 9645678
TI  - The effect of cell-matrix interaction on parathyroid hormone (PTH) receptor
      binding and PTH responsiveness in proximal renal tubular cells and osteoblast
      like cells.
AB  - The interaction of cells with the surrounding extracellular matrix (ECM) or
      basement membrane (BM) brings about profound changes in cellular biological
      responses, such as cell differentiation, proliferation, and gene expression. We
      studied the effect of ECM on PTH receptor binding and on biological responses
      mediated by PTH, in two cell preparations: 1) the proximal tubular OK opossum
      kidney cell line; and 2) MC3T3-E1 cells, a clonal line of nontransformed murine
      osteoblasts. Cells were plated on either plastic surfaces or on tissue culture
      dishes coated with specific ECM components. In both cell types plated on collagen
      type IV (Col-IV), PTH receptor binding, on day 4 of culture, was markedly
      diminished, when compared with cells on plastic (approximately 45% inhibition, P
      < 0.01). In addition, Col-IV dose dependently inhibited cAMP generation
      stimulated by PTH (P < 0.001 vs. plastic), whereas cAMP generation by PGE2,
      cholera toxin, and forskolin was not altered. In Northern blot analysis, a
      PTH/PTH-related-protein receptor messenger RNA transcript was detected in both
      the kidney and bone cells. However, only OK cells manifested a decreased
      abundance of receptor messenger RNA when plated on Col-IV, compared with plastic.
      The physiological significance of inhibited cAMP production by Col-IV was
      evaluated by measuring the influence of different matrices on the activity of
      Na+/H+ exchanger (NHE) in OK cells and cell mitogenic activity in MC3T3-E1 cells
      (both responses are negatively modulated by cAMP). OK cells plated on Col-IV
      showed 70% inhibition of NHE, compared with cells plated on plastic (P < 0.01).
      PTH inhibits NHE activity in cells on plastic but stimulates exchanger activity
      by 40% in cells plated on Col-IV. In MC3T3-E1 cells grown on plastic, PTH exerts
      a dose-dependent antiproliferative effect, which is mediated by cAMP. This effect
      is mitigated when cells are grown on Col-IV (40-50% less antiproliferative
      effect). In summary, Col-IV, a maj or BM constituent, has a profound inhibitory
      effect on PTH binding and PTH-mediated biological responses in both kidney
      tubular cells and osteoblasts. Altered cellular function by Col-IV may be of
      physiological relevance in states associated with altered composition of BM or
      expansion of ECM (e.g. diabetes mellitus and interstitial fibrosis).

PMID- 9645679
TI  - Expression of interferons-alpha and -gamma in testicular interstitial tissue and
      spermatogonia of the rat.
AB  - The testis is divided into two compartments: the seminiferous tubules and the
      interstitial tissue. The latter essentially consists of the blood and lymphatic
      vessels, testosterone-producing Leydig cells, and testicular macrophages. In the
      exploration of the testicular antiviral defense system, we initially searched for
      interferon (IFN) production by the seminiferous tubule cells. The site of virus
      entry into the testis is probably the interstitial compartment; thus, it is
      important to know whether and how the cells in this compartment are protected
      against viral infection. In addition, as germ cell precursors (spermatogonia) are
      only partially protected by the blood-testis barrier, it was important to explore
      the antiviral capability of these cells. In this study we searched for IFN
      production by Leydig cells, testicular macrophages, and spermatogonia after
      exposure to Sendai virus. We also investigated the effect of viral exposure on
      testosterone production by Leydig cells. Our results show that spermatogonia do
      not constitutively express IFNs and give a very poor response to the virus. In
      contrast, testicular macrophages constitutively produced type I IFNs, and this
      production was markedly stimulated by Sendai virus. Leydig cells produced twice
      as much type I IFNs as testicular macrophages after viral exposure, and they were
      the only cells producing both IFNalpha and -gamma, with these IFNs being
      dramatically induced/ increased in response to exposure to the virus.
      Furthermore, incubation of Leydig cells with the Sendai virus stimulated
      testosterone production. In conclusion, this study further establishes the
      topography of IFN expression within the testis. This allows us to hypothesize
      that the potential antiviral system represented by Leydig cells and, to a lesser
      extent, by macrophages plays a key role in protecting both androgen production
      and spermatogenesis.

PMID- 9645680
TI  - The intracerebroventricular injection of interleukin-1beta blunts the
      testosterone response to human chorionic gonadotropin: role of prostaglandin- and
      adrenergic-dependent pathways.
AB  - The present work extends our previous report that the intracerebroventricular
      (i.c.v.) injection of interleukin-1beta(IL-1beta, 80 ng) significantly blunted
      the testosterone response to 1 U/kg human CG (hCG), an effect that we attributed
      to the stimulation of inhibitory pathways connecting the hypothalamus to the
      testes. Systemic blockade of prostaglandin-dependent pathways with ibuprofen
      (alpha-methyl-4-[2-methylpropyl]benzeneacetic acid; sodium salt), which did not,
      in itself, alter the stimulatory effect of hCG on testosterone release in control
      rats, modestly, but significantly (P < 0.05) reversed the inhibitory influence of
      IL-1beta. In contrast, blockade of brain receptors for CRF was unable to alter
      the effect of IL-1beta, as were lesions of the ventromedial hypothalamic nucleus,
      a brain area implicated in the control of ovarian function. Blockade of beta
      adrenergic receptors significantly prevented the decrease in testicular
      responsiveness induced by the i.c.v. injection of IL-1beta. Finally, the central
      injection of the beta-adrenergic agonist isoproterenol, as well as that of
      norepinephrine, mimicked the ability of icv IL-1beta to blunt testicular
      secretory activity and produced a marked (P < 0.01) decrease in the response to
      hCG within 5 min of their administration. We propose that the explanation that
      best fits our findings is that the i.c.v. injection of IL-1beta activates a
      neural, catecholamine-dependent pathway that connects the brain and the testes
      independently of the pituitary.

PMID- 9645681
TI  - Inhibition of prostaglandin production by nimesulide is accompanied by changes in
      expression of the cassette of uterine labor-related genes in pregnant sheep.
AB  - The present study was designed to characterize effects of inhibiting PG
      production by infusing nimesulide (CAS 51803-78-2) on PGE2 production and
      expression of uterine labor-related genes in pregnant sheep. Myometrium,
      endometrium, and placenta were collected following 6 h of i.v. nimesulide or
      vehicle infusion. Infusions were commenced 9 h after onset of spontaneous term
      labor. Tissues were also collected from term control ewes not in labor. PGE2 was
      measured in fetal plasma by RIA. ER, OTR, Hsp 70 and 90, cPLA2, and PGHS-2
      messenger RNA (mRNA) abundance in myometrium, endometrium, and PGHS-2 in placenta
      were quantified by Northern blot analysis. Fetal plasma PGE2 decreased during
      nimesulide infusion (P < 0.05). ER, OTR, Hsp 70, and Hsp 90 mRNA increased during
      spontaneous term labor in vehicle infused ewes in both myometrium and
      endometrium. In myometrium after nimesulide infusion, OTR and Hsp 70 mRNA
      decreased significantly (P < 0.05) compared with vehicle infused animals, but the
      decrease in Hsp 90 and ER mRNA fell outside the level of significance. In the
      endometrium, nimesulide produced a decrease in ER and OTR mRNA (P < 0.05)
      compared with vehicle infused animals, but the changes in Hsp 90 and 70 mRNA fell
      outside the level of significance. Nimesulide reversed the up-regulation of PGHS
      2 mRNA that occurred in myometrium, endometrium, and placenta during vehicle
      infusion (P < 0.05). cPLA2 was only elevated in the endometrium in vehicle
      infused ewes and did not change in either endometrium or myometrium after
      nimesulide infusion. CONCLUSIONS: Inhibition of PG production resulted in
      decreased fetal plasma PGE2. The decreased abundance of mRNA for several of the
      well described cassette of utero-placental labor-related genes following
      nimesulide inhibition may result from altered PG production.

PMID- 9645682
TI  - Gonadotropin-releasing hormone pulses are required to maintain activation of
      mitogen-activated protein kinase: role in stimulation of gonadotrope gene
      expression.
AB  - The present study examined the effect of alterations in GnRH signal pattern
      (pulsatile vs. continuous; pulse frequency) on mitogen-activated protein kinase
      (MAPK) activity and whether MAPK plays a role in regulating gonadotrope gene
      expression. Pituitary MAPK activity was measured by immunoblot, using a phospho
      specific MAPK antibody, corrected to the amount of total MAPK per sample. In vivo
      studies were conducted in adult castrate testosterone-replaced male rats (to
      suppress endogenous GnRH). Animals received pulsatile or continuous GnRH (or BSA
      saline for controls) via jugular cannulas. Initial studies revealed that
      pulsatile GnRH stimulated a dose-dependent rise in MAPK activity (30 ng, 2-fold
      increase; 100 ng, 4-fold; 300 ng, 8-fold) 4 min after the pulse. The effect of
      pulsatile vs. continuous GnRH was examined by administering 50-ng pulses (60-min
      interval) or a continuous infusion (25 ng/min) for 1, 2, 4, or 8 h. Pulsatile
      GnRH stimulated a 2- to 4-fold rise in MAPK activity (P < 0.05 vs. controls) that
      was maintained over the 8-h duration. In contrast, continuous GnRH only increased
      MAPK activity (2- to 3-fold; P < 0.05 vs. controls) for 2 h, with MAPK activity
      returning to baseline at later time points. The effect of GnRH pulse frequency on
      MAPK activation was determined by giving GnRH pulses (50 ng) at 30-, 60-, or 120
      min intervals for 8 h. Maximal increases (3-fold vs. controls; P < 0.05) were
      seen after 120-min pulses, with faster (30- to 60-min interval) pulses
      stimulating 2-fold increases in MAPK activity (P < 0.05 vs. controls and 120-min
      GnRH pulse group). The role of MAPK activation on gonadotrope (alpha, LHbeta,
      FSHbeta, and GnRH receptor) gene expression was determined in vitro. Preliminary
      studies demonstrated that the MAPK inhibitor, PD-098059 (50 microM), completely
      blocked GnRH-induced increases in MAPK activity in adult male pituitary cells.
      Further studies revealed that PD-098059 blocked gonadotrope messenger RNA (mRNA)
      responses to pulsatile GnRH (100 pg/ml, 60-min interval, 24-h duration) in a
      selective manner, with alpha, FSHbeta, and GnRH receptor (but not LHbeta) mRNA
      responses being suppressed. These results show that a pulsatile GnRH signal is
      required to maintain MAPK activation for durations of longer than 2 h, and that
      slower frequency pulses are more effective. Further, MAPK plays a crucial role in
      alpha, FSHbeta, and GnRH receptor mRNA responses to pulsatile GnRH. Thus,
      divergent MAPK responses to alterations in GnRH signal pattern may be one
      mechanism involved in differential regulation of gonadotrope gene expression.

PMID- 9645683
TI  - Adrenal steroid regulation of neurotrophic factor expression in the rat
      hippocampus.
AB  - Adrenal steroids and neurotrophic factors are important modulators of neuronal
      plasticity, function, and survival in the rat hippocampus. Adrenal steroids act
      through two receptor subtypes, the glucocorticoid receptor (GR) and the
      mineralocorticoid receptor, and activation of each receptor subtype has distinct
      biochemical and physiological consequences. Adrenal steroids may exert their
      effects on neuronal structure and function through the regulation of expression
      of neurotrophic and growth-associated factors. We have examined adrenal steroid
      regulation of the neurotrophins brain-derived neurotrophic factor, neurotrophin
      3, and basic fibroblast growth factor, as well as the growth associated protein
      GAP-43, through activation of GR or mineralocorticoid receptor with selective
      agonists. Our findings indicated that in CA2 pyramidal cells, adrenalectomy
      resulted in decreases in the levels of basic fibroblast growth factor and
      neurotrophin-3 messenger RNA, which were prevented by activation of
      mineralocorticoid but not glucocorticoid receptors. Adrenalectomy-induced
      increases in GAP-43 and brain-derived neurotrophic factor messenger RNA levels
      could be blocked by activation of glucocorticoid receptors in CA1, but not in
      CA3, pyramidal cells. Thus the extent to which adrenal steroids regulate
      hippocampal neurotrophic and growth-associated factors, appears to be dependent
      both on the adrenal steroid receptor subtype activated and on the hippocampal
      subregion examined.

PMID- 9645684
TI  - Intestinal adaptation after extensive small bowel resection: differential changes
      in growth and insulin-like growth factor system messenger ribonucleic acids in
      jejunum and ileum.
AB  - The distal small bowel exhibits greater adaptive growth than proximal segments
      after partial small intestine resection. To explore this process, we evaluated
      adaptive cellularity, intestinal insulin-like growth factor (IGF) system
      messenger RNA (mRNA) transcripts, and effects of recombinant IGF-I treatment in
      jejunum and ileum of adult rats. Gastrostomy-fed animals underwent 80% jejuno
      ileal resection or intestinal transection and reanastomosis without resection,
      followed by infusion of human recombinant IGF-I (2.4 mg/kgXday) or vehicle. After
      7 days, resected rats demonstrated modest adaptive growth in jejunum and marked
      cell proliferation in ileum. Resection increased IGF-I mRNA in both jejunum
      (183%) and ileum (249%) and up-regulated IGFBP-4 mRNA levels in both tissues.
      IGFBP-3 mRNA fell significantly in ileum after resection. IGF-I infusion modestly
      increased ileal cellularity after resection, but had no effect in jejunum. IGF-I
      markedly increased IGFBP-3 mRNA levels in jejunum after both transection and
      resection. These data confirm that bowel resection induces greater adaptive
      growth in ileum than jejunum. IGF-I administration modestly increases ileal, but
      not jejunal, growth after resection. Increased levels of intestinal IGF-I and
      IGFBP-4 mRNA suggest roles for IGF-I and IGFBP-4 in mediating small bowel
      adaptation. Higher levels of jejunal IGFBP-3 mRNA may be related to limited
      jejunal vs. ileal growth after extensive jejuno-ileal resection.

PMID- 9645685
TI  - Effects of aging and a high fat diet on body weight and glucose tolerance in
      glucagon-like peptide-1 receptor -/- mice.
AB  - Disruption of glucagon-like peptide-1 (GLP-1) receptor signaling in mice results
      in mild glucose intolerance, principally due to elimination of the incretin
      effect of GLP-1. Despite the inhibitory effects of GLP-1 on food intake, 6- to 8
      week-old GLP-1 receptor -/-(GLP-1R-/-) mice were not obese and did not exhibit
      disturbances of feeding behavior. As both diabetes and obesity frequently become
      more phenotypically evident in older rodents, we studied the consequences of
      aging and a high fat diet on glucose control and body weight in GLP-1R-/- mice.
      No evidence of obesity or deterioration in glucose control was detected in 11-
      and 16-month-old GLP-1R-/- mice (mean weight, 34.7 +/- 2.0, 30.5 +/- 1.5, and
      34.6 +/- 2.8 g in male and 25.3 +/-1.6, 28.4 +/-1.2, and 31.9 +/- 2.9 g in female
      GLP-1R+/+, GLP-1R+/-, and GLP-1R-/- mice, respectively; P = NS). After 18 weeks
      of high fat feeding, GLP-1R-/- mice gained similar (males) or less (females)
      weight than age- and sex-matched CD1 controls. No significant deterioration in
      glucose tolerance was observed after high fat feeding in GLP-1R-/- mice. These
      observations demonstrate that long term disruption of GLP-1 signaling in the
      central nervous system and peripheral tissues of older mice is not associated
      with the development of obesity or deterioration in glucose homeostasis.

PMID- 9645686
TI  - Insulin induction of protein kinase C alpha expression is independent of insulin
      receptor Tyr1162/1163 residues and involves mitogen-activated protein kinase
      kinase 1 and sustained activation of nuclear p44MAPK.
AB  - We examined the effect of insulin on protein kinase C alpha (PKCalpha) expression
      and the implication of the mitogen-activated protein kinase kinase 1 mitogen
      activated protein kinase (MAPK) pathway in this effect. PKCalpha expression was
      measured by quantitative RT-PCR and Western blotting using Chinese hamster ovary
      (CHO) cells overexpressing human insulin receptors of the wild type (CHO-R) or
      insulin receptors mutated at Tyr1162/1163 autophosphorylation sites (CHO-Y2). In
      CHO-R cells, insulin caused a time- and concentration-dependent increase in
      PKCalpha messenger RNA, with a maximum at 6 h and 10-(8)M insulin. This increase
      involved a transcriptional mechanism, as it was not due to stabilization of
      PKCalpha messenger RNA and was associated with a similar increase in the
      immunoreactive PKCalpha level. Insulin induction of PKCalpha expression involved
      the MEK1MAPK pathway, as it was 1) almost completely suppressed by the potent
      MEK1 inhibitor PD98059, 2) mimicked by the dominant-active MEK1 (S218D/S222D)
      mutant, and 3) associated with sustained MAPK activation. In CHO-Y2 cells in
      which the early phase of MAPK activation by insulin was lost and only the late
      and sustained phase of activation was observed, insulin signaling of PKCalpha
      expression was preserved and again involved the MEK1-MAPK pathway. Moreover, we
      show that in both CHO-R and CHO-Y2 cells, insulin stimulation of PKCalpha gene
      expression was associated with prolonged activation of nuclear p44MAPK. These
      results indicate that induction of PKCalpha gene expression by insulin is
      independent of Tyr1162/1163 autophosphorylation sites and correlates with
      sustained activation of p44MAPK at the nuclear level.

PMID- 9645687
TI  - Improvement of erectile function in diabetic rats by insulin: possible role of
      the insulin-like growth factor system.
AB  - Erectile dysfunction is commonly experienced in men with diabetes mellitus. We
      report that the intracavernous pressure (ICP) rise in diabetic rats was 55% of
      the control and returned to normal following insulin (I) or insulin plus free
      oxygen scavenger (I + S) treatment. Insulin-like growth factor (IGF) binding
      protein (IGFBP) -3, -4, and -5 messenger RNA (mRNA) levels in the major pelvic
      ganglia (MPG) of diabetic rats were elevated by 2-fold, 2.6-fold, and 2.5-fold,
      respectively. Both I and I + S returned IGFBP-4 and 5 mRNA levels to normal,
      whereas IGFBP-3 gene expression was severely inhibited. IGFBP-2 gene expression
      was greatly inhibited by diabetes and was unresponsive to treatment. In the penis
      of diabetic rats, IGFBP-2 and -4 mRNA levels were low, whereas IGFBP-3 mRNA
      levels were elevated 10-fold. These effects were reversed by I and I + S. I and I
      + S also corrected the IGFBP-3 expression pattern. IGF-I gene expression in the
      penis and MPG was not significantly increased (P < 0.05) by diabetes and returned
      to normal levels following I or I + S treatment. Because IGFs are potent
      regulatory factors in vascular tone, this newly described activity of insulin may
      play an important role in the improvement of erectile function seen clinically
      and in animal models.

PMID- 9645688
TI  - Antigen-presenting dendritic cells as regulators of the growth of thyrocytes: a
      role of interleukin-1beta and interleukin-6.
AB  - An accumulation of antigen-presenting dendritic cells (DC) in the thyroid gland,
      followed by thyroid autoimmune reactivity, occurs in normal Wistar rats during
      iodine deficiency, and spontaneously in diabetic-prone Biobreeding rats. This
      intrathyroidal DC accumulation coincides with an enhanced growth rate and
      metabolism of the thyrocytes, suggesting that both phenomena are related. Because
      DC are known to regulate the hormone synthesis and growth in other endocrine
      systems (i.e. the pituitary, the ovary, and the testis), we tested the hypothesis
      that DC, known for their superb accessory cell function in T cell stimulation,
      act as regulators of thyrocyte proliferation (and hormone secretion). We
      investigated the effect of (Nycodenz density gradient) purified splenic DC from
      Wistar rats on the growth rate of and thyroid hormone secretion by Wistar thyroid
      follicles (collagenase dispersion) in culture. Various numbers of DC and
      follicles were cocultured during 24 h. The proliferative capacity of thyrocytes
      was measured by adding tritiated thymidine (3H-TdR) and bromodeoxyuridine, the
      hormone secretion into the culture fluid was measured by using a conventional T3
      RIA. Furthermore, antibodies directed against interleukin-1beta (IL-1beta), IL-6,
      and tumor necrosis factor-alpha (TNF-alpha) were added to these cocultures to
      determine the role of these cytokines in a possible DC regulation of thyrocyte
      growth. Cocultures were also carried out in the presence of antimajor
      histocompatibility complex-class I (MHC I), anti-MHC II, antiintercellular
      adhesion molecule-1 (ICAM-1), and antilymphocyte function-associated antigen
      1alpha (LFA-1alpha) antibodies to possibly interfere with DC-thyrocyte
      interactions. The addition of DC to thyroid follicles clearly inhibited their 3H
      TdR uptake, particularly at a 10:1 ratio, in comparison to follicle cultures
      alone, both under basal conditions and after TSH stimulation (75 +/- 7% and 49 +/
      11% reduction, respectively, n = 4). The follicle T3 secretion (after TSH
      stimulation) was also suppressed by DC in this system, but to a lesser extent (at
      best at an 1:1 ratio, 25 +/- 7% reduction, n = 4). The DC-induced inhibition of
      thyroid follicle growth was totally abrogated after addition of anti-IL-1beta
      antibodies; anti-IL-6 only had effect on the DC inhibition of non-TSH-stimulated
      thyrocytes, whereas anti-TNF-alpha demonstrated no effect at all. The antibodies
      to MHC and to adhesion molecules had also no effect on this DC-induced growth
      inhibition. The effect of the different anti-cytokine and anti-adhesion
      antibodies on the T3 secretion from thyroid follicles was not investigated. The
      clear inhibition of thyrocyte growth by splenic DC (classical antigen-presenting
      cells) again demonstrates the regulatory role of DC in endocrine systems.
      Proinflammatory cytokines such as IL-1beta and IL-6 are important mediators in
      this regulation. The here shown dual role of DC represents a link between the
      immune and endocrine system, which may form the gateway to the understanding of
      the initiation of thyroid autoimmune reactions and the thyroid autoimmune
      phenomena seen in iodine deficiency.

PMID- 9645689
TI  - Prostaglandin E2, interleukin 1alpha, and tumor necrosis factor-alpha increase
      human osteoclast formation and bone resorption in vitro.
AB  - Prostaglandin E2 (PGE2) and the cytokines interleukin (IL) 1alpha and tumor
      necrosis factor (TNF)alpha increase bone resorption in vivo, but the effect of
      these agents on osteoclastic bone resorption has never been studied in an in
      vitro human system. Our recently described human bone marrow culture system, in
      which osteoclasts are generated (vitronectin and calcitonin receptor-positive
      cells which resorb bone), was used to study the effects of these agents. Addition
      of indomethacin to macrophage colony-stimulating factor (M-CSF)-treated cultures
      nearly abolished osteoclast parameters, indicating that prostaglandins are
      virtually essential for human osteoclast formation. Additionally, PGE2 dose
      responsively increased osteoclast numbers and bone resorption. The effects of M
      CSF and PGE2 are independent, as demonstrated by unaltered PGE2 concentrations in
      culture supernatants in spite of the dose-responsive increase in osteoclast
      parameters in response to M-CSF. The generation of osteoclasts in the presence of
      PGE2 occurred in favor of CD 14-positive macrophage formation. IL 1alpha and
      TNFalpha increased osteoclast parameters in a dose-responsive manner. Maximum
      stimulation yielded culture supernatant levels of PGE2 approximately the same as
      those concentrations of exogenous PGE2 that dramatically induced osteoclast
      formation. This osteoclast-inducing effect was inhibited both by indomethacin and
      by the specific inhibitor of inducible prostaglandin G/H synthase, NS398, and
      this was reversed by addition of exogenous PGE2. These results demonstrate
      unequivocally that IL 1alpha and TNFalpha enhance human osteoclast formation and
      suggest that they mediate their effects through PGE2.

PMID- 9645690
TI  - Alpha, beta, and gamma mineralocorticoid receptor messenger ribonucleic acid
      splice variants: differential expression and rapid regulation in the developing
      hippocampus.
AB  - Two different types of corticoid receptor molecules bind circulating
      corticosterone in brain: mineralocorticoid receptors (MR) and glucocorticoid
      receptors. MR exhibit the highest affinity for the endogenous glucocorticoid in
      the rat, corticosterone. During development, low corticosterone levels influence
      neurogenesis, and these effects are probably MR mediated. Three MR complementary
      DNA clones, alpha, beta, and gamma, have been identified in the rodent. All of
      these MR complementary DNA clones have identical coding regions, but differ
      significantly at the 5'-untranslated end. Although the functional significance of
      these three messenger RNA (mRNA) species remains unknown, one hypothesis is that
      they reflect the ability of the brain to regulate the expression of MR, allowing
      multiple factors to differentially control transcription in a tissue- and time
      specific manner. To investigate this possibility, we examined the presence of
      these distinct mRNA forms in the developing rat hippocampus (HC). In situ
      hybridization with specific alpha, beta, and gamma complementary RNA probes was
      performed in the HC of 3-, 5-, 7-, 12-, 14-, 28-, 35-, and 65-day-old animals. We
      found that there is differential expression of these forms in each of the HC
      subfields from infancy to adulthood. y expression appears to be associated with
      periods of cell birth and increased axonal sprouting. beta expression, on the
      other hand, may be best linked to periods of synaptogenesis, growth of
      commissural and associative terminal fields, and possibly active pruning. To
      explore the possibility that the differential gene expression may be related to
      corticosterone environment, adrenalectomy was performed. A rapid modulation of
      the MR mRNA variants (14 h) in an age- and site-specific fashion was seen. These
      findings suggest that the variation in expression and regulation during
      development of the multiple MR transcripts could reflect a complex pattern of
      developmental regulation that may involve a multitude of factors unique to each
      postnatal age and to the different neuronal populations within the hippocampal
      formation.

PMID- 9645691
TI  - 5-Lipoxygenase metabolites inhibit bone formation in vitro.
AB  - The leukotrienes and peptido-leukotrienes are 5-lipoxygenase (5-LO) metabolites
      of arachidonic acid that appear to have unique effects on bone, distinct from
      those of the prostaglandins. Application of exogenous leukotrienes in vitro and
      in vivo results in increased osteoclast formation and bone resorption. While 5-LO
      metabolites of arachidonic acid clearly stimulate osteoclastic bone resorption,
      little is known concerning their effects on osteoblastic bone formation. We
      examined the effects of the 5-LO metabolites 5-HETE, the leukotriene LTB4 and, as
      representative of the peptido-leukotrienes, LTD4 on the formation of mineralized
      nodules of fetal rat calvarial cells in the presence of dexamethasone and
      recombinant human bone morphogenetic protein-2 (rhBMP-2). We also examined the
      effects of these 5-LO metabolites on alkaline phosphatase activity and cell
      proliferation in these cultures and the effects of 5-HETE and LTB4 on cultured
      explants of neonatal murine calvariae. We found that the bone-forming capacity of
      osteoblasts was impaired when cells were cultured in the presence of 5-LO
      metabolites. These data indicate that metabolites of the 5-LO pathway are
      negative regulators of bone formation. The continued presence of these
      metabolites in the bone environment might account, in part, for the bone loss
      associated with chronic inflammatory conditions.

PMID- 9645692
TI  - The endothelin subtype A receptor undergoes agonist- and antagonist-mediated
      internalization in the absence of signaling.
AB  - The potent vasoconstrictor and mitogen to smooth muscle cells, endothelin-1 (ET
      1), acts via two distinct G protein-coupled receptors, subtype A (ETAR) and
      subtype B, that are coupled primarily to the Gq-phospholipase C signaling
      pathway. It is known that ET-1 binding to ETAR promotes internalization, with
      subsequent degradation of at least a portion of the bound ligand. To investigate
      whether signaling is required for endocytosis, we developed stably transfected
      lines of human embryonic kidney 293 cells expressing wild-type ETAR and a
      receptor chimera (ETARC) in which the C-terminal cytoplasmic tail to ETAR was
      replaced with that of the lutropin receptor, another G protein-coupled receptor,
      but one which signals through the Gs-adenylyl cyclase pathway. ETARC binds ET-1
      like ETAR, but is deficient in signaling. Using a combined concanavalin A/sucrose
      gradient centrifugation technique to separate plasma membranes from other
      cellular membranes, we found that [125I]ET-1 is rapidly internalized into ETAR
      expressing cells at 37 C (t1/2 for internalization = 5 min; endocytic rate
      constant = 0.1 min(-1); ETARC-expressing cells also internalize [125I]ET-1,
      albeit at a somewhat slower rate than wild-type receptor (t1/2 for
      internalization = 15 min; endocytic rate constant = 0.03 min(-1). Using
      immunofluorescence confocal microscopy and an antibody developed to the N
      terminal region of ETAR, qualitatively similar results were obtained. In
      addition, it was found using confocal microscopy that the ETAR-selective
      antagonist, BQ123, also promoted rapid internalization in cells expressing ETAR.
      These results establish that inositol 1,4,5-trisphosphate signaling is not
      required for ligand-mediated internalization of ETAR and suggest that a receptor
      conformational change is necessary. Moreover, the finding that BQ123 promotes
      ETAR internalization is novel and has potentially important implications in its
      clinical use.

PMID- 9645693
TI  - Sexual differentiation of aromatase activity in the rat brain: effects of
      perinatal steroid exposure.
AB  - Androgens regulate aromatase activity in the medial preoptic area and other
      components of the brain circuit that mediates male sexual behavior. The levels of
      aromatase activity within these brain regions are greater in males than in
      females. As the activation of copulation requires aromatization of testosterone
      to estradiol, this quantitative enzymatic difference between sexes could
      contribute to the greater behavioral response displayed by males. The present
      study was designed to test the hypothesis that gender differences in brain
      aromatase activity of adult rats are dependent on the sexual differentiation of
      the brain that occurs during perinatal exposure to gonadal hormones. Aromatase
      activity was measured in vitro in microdissected brain samples using a sensitive
      radiometric assay. We examined the effect of pre- and postnatal treatment with
      testosterone propionate or diethylstilbestrol on basal levels and androgen
      responsiveness of aromatase in adults. In addition, we examined what effect
      prepubertal gonadectomy exerts on enzyme regulation. Our results demonstrate that
      perinatal treatments with gonadal hormones that are known to differentiate sexual
      behavior can completely masculinize the capacity for aromatization in the adult
      female. The process that differentiates aromatase expression appears to depend on
      androgen exposure and, in part, local estrogen synthesis, as diethylstilbestrol
      was able to substitute for testosterone propionate. We also observed that
      prepubertal gonadectomy reduced the levels of aromatase activity measured in
      adult brain, suggesting that gonadal hormones that are secreted during puberty
      may enhance the expression of aromatase activity in adulthood. From this study,
      we conclude that testosterone and/or its estrogenic metabolites act on the
      developing brain to determine the gender-specific capacity for aromatization and
      to regulate androgen responsiveness within components of the neural circuitry
      that mediates male sexual behavior.

PMID- 9645694
TI  - Bidirectional transcription regulation of glial fibrillary acidic protein by
      estradiol in vivo and in vitro.
AB  - Glial fibrillary acidic protein (GFAP) expression shows cyclic variation in the
      rat hypothalamus and hippocampus during the normal estrous cycle. To elucidate
      the role of transcription in the regulation of GFAP, we examined levels of GFAP
      intron 1 by in situ hybridization in the hypothalamus and hippocampus of normal,
      cycling rats. On the afternoon of proestrus, when plasma estradiol levels are
      highest, GFAP transcription and messenger RNA were both increased in the arcuate
      nucleus of the hypothalamus and decreased in the outer molecular layer of the
      dentate gyrus. In the hilus of the hippocampus, neither GFAP transcription nor
      messenger RNA changed during the estrous cycle. In vitro, astrocytes showed
      bidirectional responses, such that estradiol treatment increased GFAP
      transcription in monotypic astrocytic cultures but decreased GFAP transcription
      in astrocytes cocultured with neurons. The functionality of an estrogen response
      element in the 5'-upstream region of the GFAP promoter was established by site
      directed mutagenesis and binding of human recombinant estrogen receptor in gel
      shift assays. We conclude that estrogen may act directly upon astrocytes by
      estrogen receptor binding, and that the direction of the transcriptional response
      is influenced by astrocyte-neuron interactions.

PMID- 9645695
TI  - Hypothalamo-pituitary disconnection of the late-gestation ovine fetus results in
      profound changes in cortisol secretion that are not reflected in commensurate
      changes in adrenocorticotropin secretion.
AB  - A prepartum increase in fetal glucocorticoid concentrations is essential for the
      perinatal transition to extrauterine life for many mammalian species. In the case
      of the sheep, this increase in cortisol is also the trigger for parturition, and
      depends upon an intact hypothalamo-pituitary unit. Fetal sheep that have
      undergone hypothalamo-pituitary disconnection (HPD) fail to have a prepartum
      cortisol surge or initiate labor, despite apparently normal fetal ACTH
      concentrations in late gestation. We have investigated whether a defect exists in
      the regulation of pulsatile neurohormone secretion in the pituitaryadrenal axis
      of the HPD sheep fetus, by comparing immunoreactive (ir) ACTH and cortisol
      secretory dynamics in intact and HPD fetuses at 126 and 145 days of gestation
      (normal gestation length, 147 days). The fetal surgery was conducted at 115 days
      of gestation. Blood samples were collected at 5-min intervals for 2 h on each
      experimental day, and the resulting irACTH and cortisol concentrations were
      analyzed by multiple-parameter deconvolution and cross-correlation analysis.
      Basal irACTH secretion was less (P < 0.01) in HPD fetuses than intact fetuses at
      126 days, but it had recovered by 145 days. There were no differences in irACTH
      half-life or the number or duration of irACTH secretory bursts between the two
      groups of fetuses or the two gestational ages (GAs). The size of the irACTH
      secretory bursts was not affected by the operation, but it increased with GA to a
      similar extent in both groups of fetuses (P < 0.01). In keeping with the
      observations for irACTH secretion, there was no effect of age or the operation on
      cortisol half-life or on the number or duration of cortisol secretory bursts. In
      contrast, there were dramatic age-related increases (P < 0.01) in the basal
      cortisol secretion rate and the size of the cortisol secretory bursts in the
      intact, but not the HPD, fetuses. Cross-correlation analysis revealed a
      significant (P < 0.01) concordance between irACTH and cortisol secretion in only
      the intact fetuses at 126 days; this was not apparent in the intact fetuses at
      145 days, or in the young or old HPD fetuses. These findings confirm a major
      defect in cortisol secretion in the late-gestation HPD fetus but suggest that
      this is not caused by defects in irACTH secretion. Together with other
      observations, these data suggest that ACTH may not be the sole, or primary,
      regulator of adrenal cortisol secretion in the late-gestation ovine fetus.

PMID- 9645696
TI  - Glucocorticoids increase vasopressin V1b receptor coupling to phospholipase C.
AB  - Vasopressin (VP) stimulates pituitary ACTH secretion after binding to V1b VP
      receptors (V1b-R) coupled to phospholipase C (PLC). This effect of VP on ACTH
      secretion, unlike that of CRH, is resistant to glucocorticoid feedback. To
      determine whether changes in V1b-R expression or signaling mediate the
      refractoriness to glucocorticoids, the effects of glucocorticoids on pituitary VP
      binding, V1b-R messenger RNA (mRNA) and VP-stimulated inositol phosphate (IP)
      formation were studied in vivo and in vitro in the rat. Dexamethasone injection
      for 7 days decreased VP binding but increased V1b-R mRNA, indicating that mRNA
      levels do not reflect receptor number. In spite of the binding loss, VP
      stimulated IP formation was enhanced in dexamethasone-treated rats, suggesting
      that glucocorticoids increase the coupling efficiency of the V1b receptor to
      phospholipase C. Pretreatment of pituitary cells in vitro with dexamethasone or
      corticosterone, also potentiated IP formation by low and high doses of VP,
      indicating that glucocorticoids act directly in the pituitary and not through
      changes in hypothalamic factors. The effect is mediated by glucocorticoid
      receptors because it was blocked by glucocorticoid but not mineralocorticoid
      antagonists. Dexamethasone potentiated the stimulation of IP by other PLC
      dependent ligands (GnRH, TRH) but not that by the calcium ionophore, ionomycin,
      suggesting a site of action between the receptor and PLC. After treatment with
      dexamethasone, in vivo or in vitro, Western blot analysis revealed marked
      increases in the GTP binding protein, Galpha(q), which may account for the
      potentiating effect of glucocorticoid on ligand-stimulated IP. The data
      demonstrate that glucocorticoids increase coupling of the V1b-R with PLC thereby
      providing a mechanism by which VP facilitates corticotroph responsiveness in
      spite of elevated levels of plasma glucocorticoids during stress.

PMID- 9645697
TI  - Unmasking of a periodic Na+ entry into glucose-stimulated pancreatic beta-cells
      after partial inhibition of the Na/K pump.
AB  - The cytoplasmic concentration of Na+ ([Na+]i) was measured in individual mouse
      beta-cells using dual wavelength microfluorometry and the indicator sodium
      binding benzofuran isophtalate. Under conditions known to induce large amplitude
      oscillations in cytoplasmic Ca2+ (1.3 mM Ca2+; 11 mM glucose), [Na+]i remained
      low and stable at 10-14 mM. Partial suppression of the Na/K pump with 50 microM
      ouabain resulted in oscillations of [Na+]i in 65% of the cells (frequency, 0.13+/
      O.O1 min(-l); amplitude, 4.4 +/-0.3 mM). The oscillations were unaffected by the
      presence of 3 microM tetrodotoxin, but disappeared when the medium was depleted
      of Ca2+ or supplemented with 10 microM methoxyverapamil. The analysis of the
      ouabain effect was facilitated by replacing extracellular Ca2+ with 5 mM Sr2+. In
      the Sr2+-containing medium, oscillations of [Na+]i were seen in more than 70% of
      the beta-cells exposed to 11 mM glucose. Ouabain (50 microM) modified the [Na+]i
      oscillations by increasing their amplitudes almost 3-fold and reducing the
      frequency from once every 3 min to once every 10 min. A relationship between
      oscillations of cytoplasmic Sr2+ and Na+ was apparent both from observations of
      similar frequencies and for the modifications obtained with ouabain. It is
      concluded that the glucose-induced oscillations of cytoplasmic Ca2+ result in a
      rhythmic entry of Na+, usually balanced by the Na/K pump. A resulting periodic
      consumption of ATP in the Na/K pump might have implications for the release of
      insulin by affecting ATP-dependent processes associated with the plasma membrane.

PMID- 9645698
TI  - Nerve growth factor processing and trafficking events following TrkA-mediated
      endocytosis.
AB  - We expressed the high affinity nerve growth factor receptor TrkA in Chinese
      hamster ovary (CHO) fibroblasts to study nerve growth factor (NGF) trafficking
      and processing events following receptor-mediated ligand internalization in a
      nonneuronal and p75 minus cell line. These stable clonal cell lines express
      approximately 2.5 x 10(5) TrkA receptors and bind 125I-NGF with high affinity (Kd
      = 4 x 10(-10) M). The TrkA receptors are autophosphorylated on tyrosine residues
      upon NGF stimulation and are capable of tyrosine phosphorylating downstream
      signaling molecules. The t1/2 of 125I-NGF internalization is 5 min, and the
      probability of an occupied TrkA receptor internalizing within 1 min at 37 C is
      9.8%. By 2 h following endocytosis, less than 10% of internalized 125I-NGF is
      degraded, as determined by TCA precipitation. Thirty minutes following ligand
      endocytosis, endocytosed 125I-NGF is delivered back to the cell surface and
      released by the cell (retroendocytosis), possibly by remaining associated with
      recycling TrkA receptors. We measured the effect of acidification on 125I-NGF
      TrkA association and found that, at pH 6, 40% of 125I-NGF remains bound. Thus,
      NGF may remain associated with the TrkA receptor at low pH conditions in the
      endosome and can thereby be targeted back to the plasma membrane for release by
      the cell. IN CONCLUSION: 1) TrkA, in the absence of p75, is fully capable of
      mediating 125I-NGF endocytosis; 2) internalized 125I-NGF is slowly and
      inefficiently degraded; 3) following internalization, 125I-NGF is
      retroendocytosed; and 4) the ability of 125I-NGF to remain receptor-associated
      during acidic conditions may provide a mechanism for its retroendocytosis via
      recycling TrkA vesicles.

PMID- 9645699
TI  - Phospholipase D- and protein kinase C isoenzyme-dependent signal transduction
      pathways activated by the calcitonin receptor.
AB  - The calcitonin receptor expressed by the porcine LLC-PK1 renal tubule cells is a
      seven-transmembrane domain, G protein-coupled receptor activating adenylyl
      cyclase and phospholipase C. Salmon calcitonin stimulated dose- and time
      dependent release of the phospholipase D-dependent phosphatidylcholine product
      [3H] choline with an EC50 = 2.5 +/-0.3 x 10(-8) M, similar to that determined for
      phosphoinositide metabolism (EC50 = 4.5 +/-1.0 x 10(-8)M). The hormone failed to
      induce release of [3H]phosphocholine and [3H]glycerophosphocholine, ruling out
      activation of phosphatydilcholine-specific phospholipase C and phospholipase A.
      Calcitonin stimulated phosphatidic acid, a product of phospholipase D-dependent
      phosphatydilcholine hydrolysis. Activation of phospholipase D was confirmed by
      release of [3H]phosphatydilethanol, a specific and stable product in the presence
      of a primary alcohol. Activation of calcitonin receptor induced diacylglycerol
      formation, with a rapid peak followed by a prolonged increase, due to activation
      of phospholipase C and of phospholipase D. Consequently, the protein kinase-C
      alpha, but not the delta isoenzyme, was cytosol-to-membrane translocated by
      approximately 50% after 20 min exposure to calcitonin, whereas protein kinase-C
      zeta, which was approximately 40% membrane-linked in unstimulated cells,
      translocated by approximately 19%. The human calcitonin receptor expressed by BIN
      67 ovary tumor cells, although displaying higher affinity for calcitonin, failed
      to activate phospholipase D and protein kinase-C in response to the hormone. This
      receptor lacks the G protein binding consensus site due to the presence of a 48
      bp cassette encoding for a 16-amino acid insert in the predicted first
      intracellular loop. This modification is likely to prevent the calcitonin
      receptor from associating to phospholipase-coupled signaling.

PMID- 9645700
TI  - Dehydroepiandrosterone decreases serum tumor necrosis factor-alpha and restores
      insulin sensitivity: independent effect from secondary weight reduction in
      genetically obese Zucker fatty rats.
AB  - Dehydroepiandrosterone (DHEA) and its sulfate ester are the most abundant
      circulating adrenal steroids in humans. Administration of DHEA has been reported
      to have beneficial effects on obesity, hyperlipidemia, diabetes, and
      atherosclerosis in obese rodents, although its effects on insulin resistance have
      not been fully elucidated. In this study, the effects of DHEA treatment on
      insulin sensitivity were investigated in genetically obese Zucker rats, an animal
      model of insulin resistance, using the euglycemic clamp technique. After 0.4%
      DHEA was administered for 10 days to female obese Zucker rats aged 16 weeks, body
      weight and plasma insulin decreased and glucose disposal rate (GDR), which was
      normally reduced in obese rats, rose significantly compared with age- and sex
      matched control obese rats. On the other hand, although the pair-fed obese rats
      also showed levels of weight reduction similar to those of DHEA-treated rats, the
      increase in GDR of DHEA-treated rats was significantly greater than in pair-fed
      rats, suggesting a direct ameliorating effect of DHEA on insulin sensitivity of
      obese rats. Serum concentration of tumor necrosis factor (TNF)-alpha, one of
      cytokines causing insulin resistance, was also reduced significantly in DHEA
      treated, but not in pair-fed obese rats. In conclusion, our results suggest that
      DHEA treatment reduces body weight and serum TNF-alpha independently, and that
      both may ameliorate insulin resistance in obese Zucker fatty rats.

PMID- 9645701
TI  - Spontaneous expression of inducible nitric oxide synthase in the hypothalamus and
      other brain regions of aging rats.
AB  - Our laboratory has demonstrated that aging in Brown-Norway rats is associated
      with decreased LH pulse amplitude and reduced GnRH and LH responsiveness to
      excitatory amino acids (EAA), presumably through the NMDA receptor (NMDAR).
      Nitric oxide (NO) is a neurotransmitter postulated to be involved in hypothalamic
      synaptic events required for normal GnRH regulation through the activation of
      neuronal nitric oxide synthase (nNOS). Paradoxically, excessive stimulation of
      nNOS by NMDAR or the expression of inducible nitric oxide synthase (iNOS) can
      lead to supraphysiological levels of NO acting as effector of apoptosis with
      resultant decreased regional neuronal function. The aims of this study were to
      determine: 1) whether aging in the preoptic area/medial basal hypothalamus is
      associated with altered NO synthesis; 2) the possible roles of the NMDAR/nNOS
      cascade and iNOS in this process; and 3) whether alterations in the levels of NOS
      isoforms are specific to this region of the brain. Brown Norway male rats (N = 5)
      at ages 1 (immature), 3 (adult), and 24 (old) months, were used for measuring
      NMDARs in hypothalamic membranes by the binding of a (3H)-NMDAR ligand. Another
      series of the same age groups of rats (N = 9) were used to determine by Western
      blot the contents of NMDAR, nNOS, and iNOS in the hypothalamus, and only iNOS in
      the frontal and parietal cortex, and cerebellum. NOS activity was measured in the
      hypothalamus by the arginine/citrulline assay. A significant decrease of NMDA
      analog binding was found in the hypothalamus from old rats as compared with adult
      (-66%) and immature animals (-57%), accompanied by a reduction in NMDAR content (
      34% and -46%, respectively). NOS activity in the hypothalamus was 67% and 100%
      higher in old rats as compared with the other two groups, although no significant
      differences were observed in nNOS content. However, hypothalamic iNOS increased
      3.8- and 7.6-fold in old rats, as compared with adult and immature, respectively.
      This increase in hypothalamic iNOS was paralleled by a rise of iNOS in other
      brain regions of old rats as compared respectively to adult and immature animals:
      3.9- and 12.8-fold, in the frontal cortex; 2.8- and 2.5-fold, in the parietal
      cortex; and 3.1- and 4.8-fold, in the cerebellum. These results show that aging
      in this rat model is associated with high NO synthesis in the hypothalamus and
      other regions of the brain, which is independent of the NMDAR/nNOS cascade. We
      speculate that increased brain levels of iNOS may lead to neurotoxicity, which
      may be involved in GnRH impaired pulsatile secretion, as well as acting as a
      possible inducer of age associated neuronal loss in cognitive related brain
      areas.

PMID- 9645702
TI  - The arcuate nucleus is the major source for neuropeptide Y-innervation of
      thyrotropin-releasing hormone neurons in the hypothalamic paraventricular
      nucleus.
AB  - Neuropeptide Y (NPY) immunoreactive (-ir) nerve fibers densely innervate
      hypophysiotropic TRH perikarya and dendrites in the hypothalamic paraventricular
      nucleus (PVN). To evaluate the contribution of the arcuate nucleus (Arc) to this
      innervation, the effect of Arc ablation by neonatal monosodium glutamate (MSG)
      treatment on the density of NPY-fibers contacting TRH neurons in the PVN was
      investigated. After the lesioned animals and vehicle-treated controls reached
      adulthood, the number of contacts between NPY-ir boutons and TRH-ir perikarya in
      the PVN was determined in double-immunostained sections. In controls, numerous
      contacts between NPY-ir terminals and TRH perikarya and dendrites were observed,
      confirming earlier findings. MSG treatment resulted in a marked reduction of the
      size of the Arc and also the number of NPY-perikarya with a concomitant reduction
      of 82.4 +/-2.1% in the relative number of NPY terminals contacting TRH perikarya
      and first order dendrites in the medial parvocellular and periventricular
      subdivisions of the PVN. In contrast, lesioning of the ascending adrenergic
      bundle in the brain stem caused no statistically significant change in the number
      of NPY-terminals in close apposition to hypophysiotropic TRH neurons in the PVN.
      These data confirm earlier findings that NPY-containing axon terminals innervate
      TRH neurons in the PVN and further demonstrate a potentially important anatomical
      relationship between NPY-producing neurons in the Arc and hypophysiotropic TRH
      neurons.

PMID- 9645703
TI  - Structure of the rat inhibin and activin betaA-subunit gene and regulation in an
      ovarian granulosa cell line.
AB  - We have isolated the rat inhibin and activin betaA-subunit gene, which is
      composed of three exons, and have characterized a 571-bp region upstream from the
      transcriptional start site that functions as a promoter in transient transfection
      studies in an ovarian granulosa cell line, GRMO2. Deletion analysis of the 571-bp
      promoter region has identified DNA sequences between -362 bp and -110 bp to be
      essential in mediating basal promoter activity and activation by forskolin (FSK)
      and/or 12-O-tetradecanoylphorbol-13-acetate (TPA). Within this region, a variant
      CRE (cAMP response element) has been identified at -120 bp. Point mutations in
      the variant CRE substantially reduce the ability of FSK and/or TPA to induce
      promoter activity in GRMO2 cells. A single nucleotide change in the variant CRE,
      which converts it to a consensus CRE, does not enhance promoter activity in
      response to FSK and/or TPA, but rather reduces promoter activity to the same
      extent as the other inactivating mutation in the variant CRE, suggesting that
      this element does not act as a classical CRE. Consistent with this,
      electrophoretic mobility shift assays performed using antibodies to a variety of
      cAMP and phorbol ester-responsive transcription factors indicate that the AP-1
      family proteins jun-B and fos-B are present in the protein complex binding to the
      variant CRE. Overexpression of jun-B and fos-B in GRMO2 cells resulted in a
      robust activation of the betaA-subunit promoter. Our results suggest that this
      novel variant CRE sequence mediates both cAMP and phorbol ester regulation
      through its interactions with AP-1family proteins.

PMID- 9645704
TI  - Characterization of the testis and epididymis in mouse models of human Tay Sachs
      and Sandhoff diseases and partial determination of accumulated gangliosides.
AB  - Beta-hexosaminidase (Hex) is an essential lysosomal enzyme whose activity is
      higher in the epididymis than in other tissues. The enzyme is also present in
      sperm and has been postulated to be required for fertilization. To better
      understand the role of Hex in reproduction, we have examined the testes and
      epididymides of mouse models of human Tay Sachs and Sandhoff diseases, produced
      by targeted disruption of the Hexa (alpha-subunit) or Hexb (beta-subunit) genes,
      respectively, encoding the enzymes Hex A (structure, alphabeta) and Hex B
      (betabeta). Testis weight, morphology, and sperm counts were unaffected in Hex
      deficient mice. In the epididymis of the Hex A-deficient Hexa-/- mice, there was
      a large increase in the size and number of lysosomes in the initial
      segment/intermediate zone. In Hexb-/- mice (Hex A and B-deficient), the
      epididymal defects were much more extensive and the cytoplasm of all cell types
      throughout the efferent ducts and epididymis was filled with pale, uncondensed,
      enlarged lysosomes. In contrast to the brain where GM2 ganglioside accumulates,
      both mutant mice accumulated two non-GM2 gangliosides in the epididymis. The
      major accumulated species was characterized by electrospray ionization tandem
      mass spectrometry. The Hexa-/- male mice were fertile; however, litter sizes were
      reduced. The Hexb-/- males were able to sire normal sized litters up to nine
      weeks of age and remained healthy until 16-20 weeks of age. The extensive
      abnormalities in the Hexb-/- mice, in contrast to region-specific effects in the
      Hexa-/-mice, indicate an important and novel role for the Hex B isozyme in the
      epididymis and a region-specific role for Hex A in the initial
      segment/intermediate zone. In contrast to other reports, our results indicate
      that Hex is not essential for fertilization in young adult male mice. To explain
      the extensive epididymal abnormalities in the Hexb-/- mice, we propose that
      substrates for Hex, such as testis-derived glycolipids, cannot be catabolized and
      accumulate in lysosomes, leading to epididymal dysfunction and abnormalities in
      the epididymal luminal environment that supports sperm maturation.

PMID- 9645705
TI  - Genetic rescue of follicle-stimulating hormone beta-deficient mice.
AB  - FSH is an alpha:beta heterodimeric pituitary glycoprotein that shares a common
      alpha-subunit with LH and TSH. To study the role of FSH in mammalian
      reproduction, we have previously generated an FSH-deficient mouse model using
      embryonic stem (ES) cell technology by introducing a null mutation in the unique
      FSHbeta gene. Male mice deficient in FSH are fertile despite their small testes
      and reduced sperm number and motility. In contrast, FSH-deficient female mice are
      infertile due to a block in folliculogenesis at the preantral stage. In this set
      of experiments, we have rescued the mutant phenotypes of FSHbeta-deficient mice
      by two genetic strategies. In the type I rescue mice, we introduced into the
      FSHbeta-deficient background a 10-kb human FSHbeta transgene that is selectively
      expressed in pituitary gonadotropes. The presence of this transgene [and thus the
      interspecies hybrid (i.e. mouse alpha:human FSHbeta hormone)] in the background
      of mouse FSHbeta deficiency completely restored the testis size, sperm number,
      and motility defects to levels comparable to those seen in control male mice. All
      of the mouse FSHbeta-deficient female mice carrying this human FSHbeta transgene
      resumed normal folliculogenesis, were fertile and delivered normal size litters.
      In the type II rescue mice, human FSH (human alpha:human FSHbeta) was ectopically
      produced from multiple tissues in the mutant background using a mouse
      metallothionein-I promoter. Whereas ectopic production of human FSH completely
      rescued the mouse FSHbeta-deficient male mice, only 3 out of 10 mouse FSHbeta
      deficient females bearing these human FSH transgenes were fertile and carried
      their pregnancies to term and parturition. We conclude that the resultant
      phenotypes due to a genetic deficiency of mouse FSHbeta can be corrected by
      appropriate expression of human FSH transgenes and that human FSHbeta gene
      regulation and function in the mouse pituitary are indistinguishable from the
      endogenous mouse FSHbeta gene.

PMID- 9645706
TI  - Dexamethasone impairs growth hormone (GH)-stimulated growth by suppression of
      local insulin-like growth factor (IGF)-I production and expression of GH- and IGF
      I-receptor in cultured rat chondrocytes.
AB  - Growth depression as a side effect of glucocorticoid therapy in childhood is
      partially mediated by alterations of the somatotropic hormone axis. The
      mechanisms of interaction between glucocorticoids and somatotropic hormones on
      the cellular and molecular level are poorly understood. In an experimental model
      of primary cultured rat growth plate chondrocytes, basal as well as GH (40 ng/ml)
      or insulin-like growth factor (IGF)-I (60 ng/ml)-stimulated growth was suppressed
      dose dependently (10(-l2)-10(-7)M) by dexamethasone (Dexa). An IGF-I antibody
      specifically and dose dependently inhibited the GH- but not the basic fibroblast
      growth factor (bFGF)-stimulated cell proliferation. GH increased the IGF-I
      concentration in conditioned serum-free culture medium; this was reversed by
      concomitant Dexa. Dexa time dependently suppressed the transcription of GH
      receptor (GHR) messenger RNA (mRNA) and down-regulated the basal and GH
      stimulated expression of GHR. Whereas no suppressive effect on basal type I IGF
      receptor (IGFR) was observed, Dexa blocked the IGF-I induced increase of IGF
      binding. These results were confirmed by GHR and IGFR immunostaining. We conclude
      that Dexa impairs the GH-induced stimulation of local secretion and paracrine
      action of IGF-I and reduces the homologous increase of IGFR and GHR expression.
      The above experiments give further insight on the interaction between GH and
      glucocorticoids on the cellular and molecular level of growth plate chondrocytes.

PMID- 9645707
TI  - Induction of ectopic corticotropic tumor in mouse embryos by exo utero cell
      transplantation and its effects on the fetal adrenal gland.
AB  - To establish an in vivo experimental system for developmental endocrinology
      research, AtT-20 cells, a corticotropic tumor cell line, were transplanted by exo
      utero manipulation into mouse embryos on embryonic day 14. The induced tumor
      secreted ACTH in situ, and the circulating ACTH level was elevated. This was the
      first model for studying the regulation of ACTH in the mouse fetal adrenal in
      vivo and the first continuous ACTH treatment model in rodent fetuses. The changes
      in the adrenal gland from the tumor-induced embryos were analyzed by light
      microscopic morphometry, immunohistochemistry for steroidogenic enzymes, and
      electron microscopy. In the treated adrenal, the volume of the inner cortical
      zone was significantly larger than that in controls. In the inner zone, cell
      density was decreased, and average cell size was increased, whereas
      bromodeoxyuridine-incorporation was not increased. The enlarged inner zone cells
      expressed an enhanced level of cytochrome P45011beta, the corticosterone
      synthesizing enzyme, and the serum corticosterone level was increased. Electron
      microscopy showed an active form of the organelles involved in steroidogenesis.
      These findings indicate that ACTH stimulates both adrenocortical hypertrophy and
      steroidogenesis in fetal mice. Potential perspectives of the novel paradigm in
      this research for molecular developmental endocrine study are discussed.

PMID- 9645708
TI  - Cloning of a membrane-spanning protein with epidermal growth factor-like repeat
      motifs from adrenal glomerulosa cells.
AB  - The three zones of adrenal cortex are thought to arise from a single
      multipotential stem cell, but the mechanisms underlying the zonal differentiation
      during embryonic development of adrenal cortex are poorly understood. Employing
      subtraction cloning strategy, we isolated three distinct clones that were
      specifically expressed in the rat glomerulosa zone. One clone, named zona
      glomerulosa specific clone, encoded a membrane-spanning protein with a signal
      peptide at the N-terminus, six epidermal growth factor-like repeat motifs, and a
      transmembrane domain near the C-terminus. It was identified as a rat homolog of
      preadipocyte factor-1 (Pref-1), a factor involved in maintaining the
      undifferentiated status of preadipocyte. Immunohistochemical studies confirmed
      the presence of Pref-1 protein in the glomerulosa zone. Detailed examination
      revealed that the zone is divided into two layers; the first is a few-cells-thick
      layer present underneath the capsule (expressing both Pref-1 protein and
      aldosterone synthase cytochrome P450), and the second layer is beneath the first
      (containing Pref-1 protein but not aldosterone synthase). Moreover, another cell
      layer was found beneath the second layer and above the fasciculata zone, whose
      cells contained no Pref-1 protein, aldosterone synthase, or 11beta-hydroxylase.
      These findings suggest that a recently reported aldosterone synthase- and 11beta
      hydroxylase-less cell layer between the two zones is composed of two kinds of
      cell: Pref-1 protein-positive and -negative cells. The level of Pref-1 message in
      the adrenal glands of animals having various pituitary-adrenal axis activities,
      as well as various plasma salt concentrations, correlated with the total number
      of glomerulosa cells. However, the specific content of Pref-1 message in a cell
      was fairly constant. When the adrenal gland was surgically enucleated and the
      remaining capsule regenerated, the level of Pref-1 transcript was significantly
      suppressed at the early phase. At this phase, only a minor population of the
      cortical cells expressed Pref-1 protein, most of these cells already expressing a
      fasciculata/reticularis-specific marker, inner zone antigen. These findings
      suggest that the capsular cells, mostly composed of the glomerulosa cells, may
      have potential for differentiating into other zones' cells, and the down
      regulation of Pref-1 expression may be an important step in the adrenal zonal
      differentiation.

PMID- 9645709
TI  - Pregnancy increases soluble and particulate guanylate cyclases and decreases the
      clearance receptor of natriuretic peptides in ovine uterine, but not systemic,
      arteries.
AB  - Pregnancy increases uterine blood flow by 30- to 50-fold and uterine production
      of cGMP by 38-fold. Moreover, cGMP causes potent vasodilatation. We hypothesized
      that pregnancy up-regulates soluble and particulate guanylate cyclases (sGC and
      pGC) in ovine uterine arteries. Activities of sGC and pGC were compared by
      measuring cGMP production (37 C; 10 min) by uterine arteries from nonpregnant (n
      = 5) and pregnant (n = 4, 120 +/- 2 days' gestation; term = 145 +/- 3 days; mean
      +/- SE) ewes after sodium nitroprusside (100 microM), atrial natriuretic peptide
      (1 microM), or C-type natriuretic peptide (CNP; 1 microM) treatment. The protein
      and/or messenger RNA expressions of sGC beta1-subunit, pGC-A, pGC-B, the
      clearance receptor of natriuretic peptide (CR), and CNP were investigated in
      uterine and systemic (renal and/or omental) arteries from nonpregnant (n = 29)
      and pregnant (n = 21; 125 +/- 2 days' gestation) ewes. The potencies of uterine
      arterial GC activities were sGC >> pGC-A > pGC-B. Activities as well as protein
      expression of sGC, pGC-A, and pGC-B in pregnant uterine arteries were increased
      48-128% above those in nonpregnant controls concomitant with a 34% down
      regulation of CR protein expression; systemic arterial protein expressions were
      unaltered. These changes in uterine arterial GC-B and CR were confirmed using RT
      PCR. Immunohistochemical staining of CNP in uterine, but not systemic, arterial
      endothelium from pregnant ewes was much stronger than that from nonpregnant ewes.
      Thus, two distinct GC pathways are present in ovine uterine artery, and both may
      be specifically upregulated during pregnancy and so contribute to the tremendous
      local increase in cGMP production during pregnancy.

PMID- 9645710
TI  - Simian virus 40 T antigen-induced gonadotroph adenomas: a model of human null
      cell adenomas.
AB  - The cell of origin of human null cell pituitary adenomas is disputed. Although
      these tumors, by definition, do not produce any of the anterior pituitary
      hormones in vivo, they have been shown to express gonadotropin subunit genes,
      release gonadotropin hormones in vitro, and express the gonadotroph-associated
      transcription factor steroidogenic factor-1. However, they demonstrate variable
      responses to releasing hormones in vitro, raising questions about their origin
      from differentiated gonadotrophs or pluripotent stem cells. In this set of
      experiments, transgenic mice carrying a temperature-sensitive mutant (TSA58) of
      simian virus 40 T antigen driven by human FSHbeta regulatory elements were
      produced. These animals developed slow growing, multifocal pituitary nodules that
      demonstrated secretion of FSH with serum FSH levels 10-fold higher in male
      transgenic animals and 5-fold higher in female transgenic animals than those in
      nontransgenic controls. Anterior pituitary pathology progressed from diffuse
      gonadotroph hyperplasia to nodular adenomas with persistent, but decreasing,
      immunoreactivity for FSHbeta and LHbeta. Ultrastructural characteristics of the
      tumors were identical to those of human null cell adenomas. These results support
      the hypothesis that human null cell adenomas are derived from gonadotrophs and
      provide an animal model for further study of this disease.

PMID- 9645711
TI  - Follicle stimulating hormone (FSH) activates the p38 mitogen-activated protein
      kinase pathway, inducing small heat shock protein phosphorylation and cell
      rounding in immature rat ovarian granulosa cells.
AB  - This study investigates the possibility that FSH activates the p38 mitogen
      activated protein kinase (MAPK) pathway in immature granulosa cells (GC). FSH
      induced the phosphorylation (activation) of p38 MAPK as evaluated by
      immunoprecipitation and by phosphorylation-specific immunoblotting. FSH-induced
      phosphorylation of p38 MAPK was blocked by pretreatment with the protein kinase A
      (PKA) inhibitor H89 and mimicked by the cAMP generating agonist forskolin,
      indicating that FSH-induced cAMP production and PKA activation are necessary and
      sufficient for the activation of p38 MAPK in GC. The small heat shock protein HSP
      27 comprises a downstream phosphorylation target for the p38 MAPK pathway. FSH
      induced phosphorylation of HSP-27 was blocked by pretreatment with the p38 MAPK
      inhibitor SB 203580, indicating that p38 MAPK activation is necessary for FSH
      induced HSP-27 phosphorylation. FSH-induced GC rounding/aggregation was blocked
      by pretreatment with SB 203580 indicating that p38 MAPK activation is necessary
      for FSH-induced GC cell shape change. The results of these experiments show that
      the p38 MAPK pathway is activated in GC in response to FSH in a cAMP/PKA
      dependent manner, and that p38 MAPK activity is required for FSH-induced HSP-27
      phosphorylation as well as rounding/aggregation in GC.

PMID- 9645712
TI  - A corticotropin-releasing hormone type I receptor antagonist delays parturition
      in sheep.
AB  - In sheep, corticotropin-releasing hormone (CRH) can stimulate the fetal release
      of ACTH to produce a cortisol surge which leads to the onset of parturition. We
      tested the hypothesis that fetal CRH is a primary factor in the onset of
      parturition in sheep by using a Type I CRH receptor antagonist, antalarmin, to
      block the endogenous action of CRH. Pregnant ewes were cannulated at 130-135 days
      of gestation. Five catheters were placed into the amniotic sac, fetal femoral
      artery, fetal tarsal vein, maternal jugular vein and carotid artery. After 5
      days' recovery, blood samples from maternal and fetal vessels were collected at
      the following times: a day before the start of infusion, at [-1, 0, 1, 2, 4, 8
      and 24]h, on the first day of infusion, and thereafter daily throughout a 10-day
      infusion. Animals (n=6 per group) received infusions into a fetal vein of either
      a vehicle comprising 1:1 mixture of ethanol and polyethoxylated castor oil
      (Cremophor EL) or antalarmin (50 g/L) in the vehicle at a rate of 0.3 mL/h. The
      plasma samples were assayed for ACTH and cortisol using commercial RIA kits.
      Fetuses infused with vehicle delivered at a mean gestational age of 141.8 +/- 0.9
      days compared with antalarmin-infused sheep at 148.8 +/- 1.6 days (P = 0.0036,
      unpaired Student's t-test). Fetal ACTH and cortisol did not change in the
      antalarmin-infused sheep after 3 days' infusion compared to significant increases
      in vehicle-infused sheep (P=0.004 and P = 0.016 respectively, ANOVA). These data
      show that CRH receptor antagonism in the fetus can delay the onset of
      parturition. It supports the hypothesis that hypothalamic CRH drives fetal
      production of ACTH and is essential for the onset of parturition triggered by a
      surge in fetal cortisol.

PMID- 9645713
TI  - Interleukin-1beta regulates pituitary follistatin and inhibin/activin betaB mRNA
      levels and attenuates FSH secretion in response to activin-A.
AB  - Activins and follistatins regulate all levels of the reproductive axis, including
      the pituitary where they stimulate and inhibit FSH production, respectively.
      Gonadotropes are known to express inhibin/activin betaB and activin-B
      (betaBbetaB) functions as an autocrine modulator of FSH production. By contrast,
      the mRNA for the activin-binding protein, follistatin, is present in most
      pituitary cells and folliculo-stellate cells may be the major source of the
      protein secreted by the anterior pituitary. Interleukin-1beta (IL-1beta) is one
      of several cytokines known to also influence the reproductive axis. IL-1beta
      inhibits the hypothalamo-pituitary-gonadal (HPG) axis by suppressing GnRH and
      gonadal steroid production. Because several pituitary cell types, including
      follistatin-producing folliculo-stellate cells, are targets of IL-1beta, cytokine
      effects on gonadotrope function were evaluated using cultured rat anterior
      pituitary cells. Activin-A (0.01 to 1 nM; 24h) increased basal FSH secretion
      approximately 2-fold. IL-1beta (0.005 to 0.5 nM) by itself had no effect on basal
      FSH secretion. However, IL-1beta attenuated FSH secretion in response to all
      concentrations of activin-A. These results suggest that the cytokine might
      stimulate the local production of a factor, such as follistatin, that antagonizes
      the action of activin-A. RNase protection analysis indicated that IL-1beta (0.005
      to 5 nM) stimulated follistatin and inhibin/activin betaB mRNA accumulation in a
      time-dependent manner. These in vitro effects of IL-1beta were blocked by the
      specific IL-1 receptor antagonist (IL-lra) and were not mimicked by either rhIL-6
      or lipopolysaccharide (LPS). Treatment of intact male rats with LPS (50 microg,
      i.v.), which increases plasma IL-1beta and induces IL-1beta expression in many
      tissues, including the pituitary, produced similar time-dependent increases in
      pituitary follistatin and inhibin/activin subunit mRNA levels. These results
      suggest that IL-1beta can modulate gonadotrope responses to activins by
      influencing the local balance of activin-B and follistatin within the pituitary.

PMID- 9645714
TI  - Histopathologic characteristics of uveal melanomas in eyes enucleated from the
      Collaborative Ocular Melanoma Study. COMS report no. 6.
AB  - PURPOSE: To describe the principal histopathologic findings in a series of 1,527
      globes with uveal melanoma and the relationship of these findings to each other.
      METHODS: All eyes enucleated in the Collaborative Ocular Melanoma Study (COMS)
      were examined independently by three ophthalmic pathologists and the findings
      recorded on a data form. A composite of findings was obtained after adjudication.
      RESULTS: The diagnosis was choroidal melanoma in 1,527 (99.7%) of 1,532 cases
      examined. Misdiagnoses were metastatic adenocarcinoma (four) and hemangioma
      (one). Spindle cell (9.0%), mixed cell (86.0%), and epithelioid cell (5.0%) types
      were observed. Medium tumors were located more posteriorly than large tumors.
      Considerable local invasion was seen: rupture of Bruch's membrane (87.7%),
      invasion of the retina (49.1%), tumor cells in the vitreous (25.2%), vortex vein
      invasion (8.9%), invasion of tumor vessels by tumor cells (13.8%), and invasion
      into emissary canals (55.0%). Overall, 81.1% demonstrated local invasion,
      excluding rupture of Bruch's membrane. Scleral invasion was present in 55.7% of
      eyes, and extrascleral extension was present in 8.2%. Mitotic activity was
      significantly reduced in eyes that had received preenucleation radiation
      treatment (P < .001). The number of macrophages in the tumor increased with
      increased pigmentation (P < .001) and increased necrosis (P < .01). CONCLUSION:
      The accuracy of diagnosis in the COMS is high, with histopathologic confirmation
      of the diagnosis at 99.7%. Extensive local invasion of the tumor was seen.
      Preenucleation irradiation significantly reduced the number of mitotic figures.
      An association was found regarding the presence of macrophages, the level of
      pigmentation, and degree of necrosis.

PMID- 9645715
TI  - The Collaborative Ocular Melanoma Study (COMS) randomized trial of pre
      enucleation radiation of large choroidal melanoma I: characteristics of patients
      enrolled and not enrolled. COMS report no. 9.
AB  - PURPOSE: To describe the baseline characteristics and status of patients enrolled
      in the Collaborative Ocular Melanoma Study (COMS) randomized clinical trial of
      pre-enucleation radiation of large choroidal melanoma conducted in the United
      States and Canada, and to compare characteristics of patients enrolled with those
      of patients with tumors of eligible size who were not enrolled in order to assess
      the generalizability of findings from the clinical trial. METHODS: For all
      patients evaluated for the clinical trial at COMS centers from November 1986
      through December 15, 1994, selected data were transmitted to the COMS
      Coordinating Center. For patients who enrolled in the clinical trial, ophthalmic
      and medical history, examination findings, and visual acuity measurements were
      recorded prior to enrollment. Standardized A-scan and contact B-scan echographic
      examinations were performed prior to enrollment, and photoechograms were
      submitted for central review for consistency with the diagnosis, independent
      measurement of the apical height of the tumor, and description of tumor
      configuration and internal reflectivity for each patient enrolled. Until January
      1992, wide-angle fundus photographs and fluorescein angiograms taken prior to
      enrollment also were submitted for central review to confirm consistency with the
      diagnosis. All data were integrated and analyzed at the COMS Coordinating Center.
      RESULTS: Of 6,078 patients with choroidal melanoma evaluated in COMS centers,
      1,860 had tumors of eligible size; of these, 1,302 (70%) were eligible for the
      clinical trial, and 1,003 (77% of eligible patients) enrolled. The two principal
      reasons for ineligibility were other primary cancer and predominantly ciliary
      body melanoma. Ineligible patients were older than eligible patients, had larger
      choroidal melanoma, and had poorer visual acuity at the time of evaluation for
      the COMS (P < .01, Wilcoxon rank sum tests). Patients eligible for the clinical
      trial had a mean age of 60 years; 56% were male; almost all (97%) were non
      Hispanic whites. Among eligible patients, mean tumor apical height was 9.5 mm and
      mean longest basal diameter was 17.2 mm. Eligible patients who enrolled in the
      trial were similar to eligible patients who did not enroll with respect to most
      factors considered. Those who enrolled had longer tumor basal diameter and better
      visual acuity in the fellow eye, more often had their primary residence in
      Canada, and less often had education beyond high school than did eligible
      patients who did not enroll (P < .05, Wilcoxon rank sum tests and chi2 tests,
      respectively). CONCLUSIONS: The COMS clinical trial of pre-enucleation radiation
      was designed to yield internally valid treatment comparisons through random
      treatment assignment at time of enrollment. Findings also have high external
      validity because a majority (54%) of all patients with tumors of eligible size,
      and a large majority (77%) of all eligible patients, were enrolled. Furthermore,
      patient characteristics are similar to those of patients included in other
      evaluations of this method of treating large choroidal melanoma. Thus, findings
      from this clinical trial apply to all patients who have large choroidal melanoma
      and satisfy COMS eligibility criteria.

PMID- 9645716
TI  - The Collaborative Ocular Melanoma Study (COMS) randomized trial of pre
      enucleation radiation of large choroidal melanoma II: initial mortality findings.
      COMS report no. 10.
AB  - PURPOSE: To report initial mortality findings from the Collaborative Ocular
      Melanoma Study (COMS) randomized clinical trial of pre-enucleation radiation of
      large choroidal melanoma. METHODS: Patients were evaluated for eligibility at one
      of 43 participating centers in the United States and Canada. Eligible consenting
      patients were assigned randomly at the time of enrollment to standard enucleation
      or to external radiation of the orbit and globe prior to enucleation. Eligibility
      was confirmed at the COMS Coordinating Center, Echography Center, and Photograph
      Reading Center. Adherence to the radiotherapy protocol was monitored at the
      Radiological Physics Center. The diagnosis of choroidal melanoma was confirmed
      following enucleation by a three-member Pathology Review Committee. Patient
      accrual began in November 1986 and was completed in December 1994; 1,003 patients
      enrolled. Patients have been followed at annual clinical examinations. Cause of
      death was coded by a Mortality Coding Committee whose members were not involved
      in the care of COMS patients; the clinical trial was monitored by an independent
      Data and Safety Monitoring Committee. RESULTS: A total of 1,003 patients were
      enrolled; 506 were assigned to enucleation alone and 497 to pre-enucleation
      radiation. Treatment groups were well balanced on baseline characteristics. Only
      nine patients were found to be ineligible after enrollment, seven in the interval
      between randomization and enucleation and two after enucleation based on
      histopathology. All but nine patients were treated as assigned; in only six of
      491 eyes treated with pre-enucleation radiation was there a major deviation from
      the radiotherapy protocol. With 5-year outcome known for 801 patients enrolled
      (80%), the estimated 5-year survival rates and 95% confidence intervals (CIs)
      were 57% (95% CI, 52% to 62%) for enucleation alone and 62% (95% CI, 57% to 66%)
      for pre-enucleation radiation. Among the baseline covariates evaluated, only age
      and longest basal diameter of the melanoma affected the prognosis for survival to
      a statistically significant degree. The risk of death among patients treated with
      pre-enucleation radiation relative to those treated with enucleation alone after
      adjustment for baseline characteristics of patients, eyes, and tumors was 1.03
      (95% CI, 0.85 to 1.25). Of 435 deaths classified by the Mortality Coding
      Committee, 269 patients had histologically confirmed melanoma metastases at the
      time of death. Estimated 5-year survival rates for this secondary outcome were
      72% (95% CI, 68% to 76%) for enucleation alone and 74% (95% CI, 69% to 78%) for
      pre-enucleation radiation. CONCLUSIONS: No survival difference attributable to
      pre-enucleation radiation of large choroidal melanoma, using the COMS
      fractionation schedule, has been demonstrated to date in this randomized trial.
      The trial had statistical power of 90% to detect a relative difference in
      mortality rates between the two treatment arms of 20% or larger. A smaller
      difference is possible, but a clinically meaningful difference in mortality
      rates, whether from all causes or from metastatic melanoma, is unlikely.

PMID- 9645717
TI  - Combined analysis of two studies using the conjunctival allergen challenge model
      to evaluate olopatadine hydrochloride, a new ophthalmic antiallergic agent with
      dual activity.
AB  - PURPOSE: To evaluate the effectiveness and safety of olopatadine hydrochloride
      and to determine its optimal concentration and the onset and duration of action
      for treating allergic conjunctivitis. Olopatadine is a new topical ophthalmic
      antiallergic agent that demonstrates activity as both an antihistamine and a mast
      cell stabilizer. Two double-masked, randomized, placebo-controlled, contralateral
      eye comparison studies were conducted using the conjunctival allergen challenge
      model. METHODS: A total of 169 subjects received 0.05% or 0.1% olopatadine. Study
      subjects were healthy adult men and women with a history of active allergic
      conjunctivitis within the previous two seasons but not receiving current
      treatment. With an allergen dose that produced signs and symptoms of allergic
      conjunctivitis at visits 1 and 2, the conjunctival allergen challenge was
      performed 27 minutes after study drug administration at the third visit (onset-of
      action challenge) and at 8 hours after study drug administration at the fourth
      visit (duration-of-action challenge). Olopatadine was administered in one eye and
      placebo in the opposite eye. Itching and redness were scored for both eyes at 3,
      10, and 20 minutes after the conjunctival allergen challenge. RESULTS: Both 0.05%
      and 0.1% concentrations of olopatadine were significantly (P < .05) more
      effective than placebo in inhibiting itching and redness at all evaluations when
      administered 27 minutes or 8 hours before the conjunctival allergen challenge.
      There were no serious or drug-related ocular or nonocular adverse events in
      either study. CONCLUSION: These findings demonstrate the rapid and prolonged (at
      least 8 hours) ocular antiallergic action of olopatadine.

PMID- 9645718
TI  - Local effects of previous conjunctival incisional surgery and the subsequent
      outcome of filtration surgery.
AB  - PURPOSE: Previous ocular surgery involving conjunctival incision is a risk factor
      for failure of filtration surgery. To determine whether using adjunctive
      antimetabolite therapy may have a rational basis, a study was performed to
      determine whether the conjunctival cellular profile was altered by such surgery.
      METHODS: After a mean follow-up of 5.9 years, filtration surgery outcomes for 35
      patients who had undergone conjunctival incisional surgery were retrospectively
      compared with 29 control and 18 matched patients who had not undergone such
      surgery. At the time of filtration surgery, a conjunctival biopsy specimen was
      obtained from all 82 patients, and these were quantitatively analyzed by light
      microscopy in a prospective manner. RESULTS: Trabeculectomy success for the
      control group (93%) was significantly higher than for the previous surgery group
      (38%) (P < .001). Compared with control tissue, conjunctiva from the patients who
      had undergone previous surgery contained more fibroblasts (P < .001, P < .05),
      macrophages (P < .01, P < .001), and lymphocytes (P = .001, P < .01) in both
      superficial and deep substantia propria (respective P values). Furthermore,
      trabeculectomy failure was associated with an increase in number of conjunctival
      fibroblasts in intraoperative specimens. CONCLUSIONS: Previous ocular surgery
      involving the conjunctiva increases the number of conjunctival fibroblasts and
      inflammatory cells. This may account for the increased risk of trabeculectomy
      failure. Perhaps on this basis, the use of adjunctive medication may be justified
      in patients who have undergone previous ocular surgery involving conjunctival
      incision.

PMID- 9645719
TI  - Identification of glaucoma-related visual field abnormality with the screening
      protocol of frequency doubling technology.
AB  - PURPOSE: To evaluate the predictive power of frequency doubling technology to
      distinguish glaucoma suspects from persons with glaucoma visual field loss.
      METHODS: A consecutive series of 76 subjects referred to a glaucoma service
      underwent perimetry in one eye with frequency doubling technology in a screening
      mode and Humphrey 24-2 threshold testing in random order, and had optic disk and
      clinical nerve fiber layer grading. RESULTS: All subjects performed perimetry
      with both instruments satisfactorily, with an average test time of 1.8 +/- 0.7
      minutes per eye for the frequency doubling technology (instrument time). Of 33
      eyes classified as abnormal by glaucoma hemifield test, 91% (30/33) were abnormal
      on frequency doubling technology (two or more abnormal locations of 17), whereas
      94% (31/33) of glaucoma suspects with normal Humphrey fields had normal results
      with frequency doubling technology. Frequency doubling technology results were
      highly correlated with Humphrey mean deviation by linear regression (r2 = .74, P
      = .047) and with corrected pattern standard deviation probability value. A
      frequency doubling technology error score for each quadrant of the field was
      highly correlated with the number of severely abnormal points per quadrant in
      Humphrey threshold tests (r2 = .63, P = .034). There was close agreement between
      clinical examination of the optic disk and nerve fiber layer and frequency
      doubling technology results. Three-level quantification of abnormality in
      frequency doubling technology results did not add to diagnostic accuracy.
      CONCLUSION: Frequency doubling technology testing shows promise as a screening
      method in glaucoma.

PMID- 9645720
TI  - Clinical classification of glaucomatous visual field loss by frequency doubling
      perimetry.
AB  - PURPOSE: To determine whether the frequency doubling perimeter (FDP) can grade
      glaucomatous visual function loss in a clinically relevant manner. Sinusoidal
      gratings < 1 cpd that undergo counterphase flicker > 15 Hz appear to have twice
      as many bands of light, a phenomenon referred to as the "frequency doubling
      illusion." Evidence suggests that this psychophysical effect is mediated in part
      by large-diameter ganglion cells, which are reported to be lost early in the
      glaucomatous disease process. A portable, commercially available FDP has already
      demonstrated high diagnostic potential for glaucoma screening. METHODS: Sixty
      four eyes of 42 glaucomatous patients and 22 eyes of 14 normal subjects were
      evaluated by means of both frequency doubling perimetry and Humphrey perimetry. A
      clinical scoring algorithm modeled after the Hodapp-Parrish-Anderson criteria for
      scoring Humphrey visual field defects was derived for the FDP at the halfway
      point of the study, and all participants were reassessed with this algorithm upon
      its completion. RESULTS: FDP mean and pattern deviation showed strong linear
      correlations with Humphrey 30-2 mean deviation (R = 0.75; P < .0001) and
      corrected pattern standard deviation values (R = 0.64; P < .0001). Despite this,
      neither global index could consistently categorize the graded glaucomatous visual
      fields in a manner consistent with the Hodapp-Parrish-Anderson criteria. The new
      FDP scoring algorithm did provide good segregation (73% precise parity, 93%
      parity within one Humphrey grade). CONCLUSIONS: Sixteen-zone frequency doubling
      perimetry can segregate glaucomatous visual field loss into pathologic categories
      approximating those obtained with Humphrey 30-2 perimetry by means of a formula
      modeled after the Hodapp-Parrish-Anderson criteria.

PMID- 9645721
TI  - In vivo quantitative measurement of posterior capsule opacification after
      extracapsular cataract surgery.
AB  - PURPOSE: To introduce a new in vivo quantitative measurement of posterior capsule
      opacification (PCO) after extracapsular cataract surgery and also to analyze the
      correlation between opacification density and the patient's visual acuity.
      METHODS: Prospectively, the opacification density value in the central 3-mm
      portion of the posterior capsule was quantitated by means of an area densitometry
      with the Scheimpflug photography system (EAS-1000). The EAS-1000 examination was
      performed on 40 eyes with clinically significant PCO both before and after
      undergoing Nd:YAG laser posterior capsulotomy, and on 10 eyes without PCO. The
      correlation between the opacification density value and the visual acuity was
      analyzed with a linear regression analysis. RESULTS: The mean opacification
      density values +/- SD were 48.8 +/- 29.5 computer-compatible tapes (CCT) steps in
      the PCO group before capsulotomy, 15.5 +/- 7.8 CCT steps in the PCO group after
      capsulotomy, and 12.9 +/- 4.9 CCT steps in the non-PCO group. The mean
      opacification density value in the PCO group before capsulotomy was significantly
      greater than that in the PCO group after capsulotomy or than that of the non-PCO
      group. A linear regression analysis determined that the opacification density
      value also correlated well with the visual acuity (R2 = .808). CONCLUSIONS: We
      have established a new in vivo quantitative measurement of PCO. Because the
      opacification density value obtained by this measurement correlated well with the
      patient's visual acuity, we consider this measurement to be useful in both the
      research and clinical management of PCO.

PMID- 9645722
TI  - Gelatinase B in proliferative vitreoretinal disorders.
AB  - PURPOSE: To investigate whether gelatinases A and B are involved in the
      pathogenesis of proliferative vitreoretinal disorders. METHODS: In a prospective
      study of 101 consecutive patients, vitreous and paired serum samples were
      obtained from 38 patients with rhegmatogenous retinal detachment complicated by
      proliferative vitreoretinopathy, 25 patients with rhegmatogenous retinal
      detachment with no proliferative vitreoretinopathy, and 38 patients with
      proliferative diabetic retinopathy. Gelatinase activities were determined by
      quantitative zymography. RESULTS: All vitreous samples contained comparable
      levels of the constitutive gelatinase A. Inducible gelatinase B was detected in
      eight (32%) of 25 vitreous samples from patients with rhegmatogenous retinal
      detachment with no proliferative vitreoretinopathy (mean +/- SD, 319.5 +/- 521.0
      scanning units), in 17 (44.7%) of 38 vitreous samples from patients with
      proliferative vitreoretinopathy (560.6 +/- 718.9 scanning units), and in 34
      (89.5%) of 38 vitreous samples from patients with proliferative diabetic
      retinopathy (1,707.2 +/- 1,220.3 scanning units). The incidence of detection of
      gelatinase B in proliferative diabetic retinopathy cases was significantly higher
      than it was in rhegmatogenous retinal detachment with no proliferative
      vitreoretinopathy and proliferative vitreoretinopathy cases (P < .001).
      Gelatinase B levels in the vitreous samples of patients with proliferative
      diabetic retinopathy were higher than the levels found in patients with
      rhegmatogenous retinal detachment with no proliferative vitreoretinopathy and in
      patients with proliferative vitreoretinopathy (P = .0152). Gelatinase A was
      detected in all the tested sera, whereas none of the tested paired serum samples
      contained detectable gelatinase B activity. CONCLUSIONS: Gelatinase B may play an
      important role in extracellular matrix degradation associated with
      neovascularization in proliferative diabetic retinopathy.

PMID- 9645723
TI  - Delusions of ocular parasitosis.
AB  - PURPOSE: To describe four cases of delusions of parasitosis in which self
      inflicted ocular trauma occurred. Delusions of parasitosis is a somatic
      delusional disorder in which patients have the irrational belief that their
      bodies are infested by parasites or other infectious organisms. Self-inflicted
      trauma can result from attempts to eliminate the supposed infestation. METHODS:
      We reviewed the case histories of four patients (one male, three females, 35 to
      45 years of age) who presented with complaints of ocular infestation but had no
      evidence of infectious ocular disease. The characteristics of these cases were
      compared with the features of delusions of parasitosis. RESULTS: All patients
      maintained their beliefs regarding infestation, despite extensive clinical and
      laboratory investigations that found no evidence of infectious diseases. Self
      inflicted eye injury, associated with attempts to eliminate the infestation,
      occurred in each case. CONCLUSIONS: The cases presented in this report are
      consistent with a diagnosis of delusions of parasitosis. The eye can be a
      principal focus of attention in this disorder, which may lead to vision loss
      caused by self-inflicted injury.

PMID- 9645724
TI  - Threshold perimetry of each eye with both eyes open in patients with monocular
      functional (nonorganic) and organic vision loss.
AB  - PURPOSE: To report a novel binocular perimetry test to identify monocular
      functional vision loss. METHODS: In a prospective study, 10 patients with
      monocular functional vision loss, 10 patients with monocular organic vision loss,
      and 10 normal subjects were tested using a Humphrey automated perimeter
      attachment that performs central threshold perimetry of both eyes in a single
      test. First, patients were tested after being told their "good" (unaffected) eye
      was being tested; this was followed by a second identical test said to be on the
      "bad" (affected) eye. Two measurements were calculated for each subject: the
      functional component (deltaF), defined as the difference (in dB) between the mean
      threshold of the first and second tests, and the organic component (deltaO), the
      difference (in dB) between the mean threshold of the unaffected and affected
      eyes. RESULTS: Patients with monocular functional vision loss produced lower
      thresholds when they thought their affected eye alone was being tested but little
      intereye difference (mean deltaF +/- SD = 17.35 +/- 7.50 dB; mean deltaO = 0.01
      +/- 1.40 dB). Patients with monocular organic vision loss had little difference
      between tests and lower thresholds in their affected eye (mean deltaF = 0.84 +/-
      1.15 dB; mean deltaO = 9.01 +/- 4.71 dB). Normal subjects demonstrated little
      intertest or intereye differences (mean deltaF = -0.15 +/- 0.78 dB; mean deltaO =
      -0.05 +/- 0.51 dB). CONCLUSION: This perimetry method effectively distinguished
      between normal subjects, patients with monocular functional vision loss, and
      patients with monocular organic vision loss.

PMID- 9645725
TI  - Choroidal melanoma: diagnosis and management.

PMID- 9645726
TI  - Histopathology of the eye in diffuse neonatal hemangiomatosis.
AB  - PURPOSE: To report the ocular presentation and histopathology of a patient with
      diffuse neonatal hemangiomatosis. METHODS: Case report. A 3.7-kg female was born
      at term. Multiple hemangiomas were present, and the patient died 39 days after
      birth. RESULTS: Widespread cutaneous and visceral hemangiomas were present.
      Ophthalmic examination disclosed bilateral eyelid and conjunctival hemangiomas.
      The right eye had multiple iris hemangiomas, hyphema, vitreous hemorrhage, and
      discrete subretinal lesions. Histopathology of the right eye demonstrated
      hemangiomas involving the iris, ciliary body, and ciliary processes. CONCLUSION:
      Diffuse neonatal hemangiomatosis was associated with ophthalmic findings of
      multiple hemangiomas involving eyelid, conjunctiva, iris, ciliary body, and
      ciliary processes.

PMID- 9645727
TI  - Cutaneous angiosarcoma with eyelid involvement.
AB  - PURPOSE: To report a clinicopathologic correlation of angiosarcoma affecting the
      eyelid skin. METHODS: An 82-year-old man developed multiple bruise-like
      maculopapular lesions, subcutaneous nodules, and diffuse edema over his scalp,
      face, and eyelids. Biopsy disclosed angiosarcoma, and the patient was treated
      with wide-field external beam radiotherapy (5,000 cGy). RESULTS: He responded to
      radiotherapy with partial regression of the tumor. Twelve months later, he
      developed extensive lymphedema secondary to the residual tumor. He was also found
      to have parotid gland and bone metastases, treated with radiotherapy. The patient
      died of widespread bone metastases 3 months later. CONCLUSIONS: Angiosarcoma is a
      rare skin tumor that has a poor prognosis despite treatment. It should be
      considered in the differential diagnosis of eyelid tumors and edema because it
      may affect only the central portion of the face.

PMID- 9645728
TI  - Rifabutin-associated uveitis in an immunosuppressed pediatric patient without
      acquired immunodeficiency syndrome.
AB  - PURPOSE: To describe a case of bilateral, symptomatic rifabutin-associated
      uveitis with hypopyon and vitreal opacities in an immunosuppressed pediatric
      patient without acquired immunodeficiency syndrome (AIDS). METHOD: Case report.
      An 8-year-old boy presented with bilateral uveitis 24 months after a bilateral
      lung transplant. RESULTS: Our patient, whose medications included rifabutin,
      clarithromycin, and immunosuppressive agents, responded to discontinuation of the
      rifabutin and initiation of intensive topical corticosteroid therapy with
      complete resolution of the uveitis. CONCLUSION: Rifabutin-associated uveitis may
      occur in a non-AIDS pediatric patient.

PMID- 9645729
TI  - Endogenous Candida endophthalmitis after induced abortion.
AB  - PURPOSE: To report two young healthy women who developed endogenous Candida
      endophthalmitis after undergoing surgically induced abortion. METHOD: Case
      reports. RESULTS: In two eyes of two patients, a diagnosis of Candida
      endophthalmitis was established by typical fundus appearance, positive vaginal
      culture, and, in one case, positive vitreous culture. After vitrectomy and
      intravitreal amphotericin B injection, one eye of one patient had a best
      corrected visual acuity of 20/200, whereas one eye of one patient, who had
      systemic corticosteroid treatment before the correct diagnosis, developed
      recurrent retinal detachment and a best-corrected visual acuity of counting
      fingers. CONCLUSIONS: Induced abortion may cause endogenous Candida
      endophthalmitis in young healthy pregnant women. Systemic corticosteroid
      treatment may increase the risk of endophthalmitis.

PMID- 9645730
TI  - Bilateral multifocal choroidal carcinoid: long-term follow-up without treatment.
AB  - PURPOSE: To report a minimally symptomatic patient with bilateral carcinoid
      tumors metastatic to the choroid who was followed up for 42 months without any
      treatment. METHOD: Case report. RESULTS: A 54-year-old white man with a history
      of bronchial carcinoid tumor had bilateral multiple carcinoid tumors metastatic
      to the choroid. Follow-up for 42 months without treatment demonstrated no growth
      of the choroidal tumors, and corrected visual acuity remained RE, 20/20 and LE,
      20/25. Systemic status also remained stable. CONCLUSIONS: Carcinoid tumors
      metastatic to the choroid may remain stationary for an extended period. Treatment
      may be deferred until tumor growth, exudative retinal detachment, or substantial
      impairment of vision develops.

PMID- 9645731
TI  - Percutaneous treatment of an orbital hydatid cyst: a new therapeutic approach.
AB  - PURPOSE: To describe the percutaneous treatment of an orbital hydatid cyst as an
      alternative approach to conventional surgery. METHODS: In a 21-year-old man with
      diplopia and right proptosis, radiologic studies disclosed a 25 x 25 x 20-mm
      purely cystic mass in the right retrobulbar area. Based on the presumptive
      diagnosis of hydatid cyst, the cyst was treated percutaneously under
      ultrasonographic guidance with aspiration, 15% hypertonic saline injection, and
      reaspiration without any complication. RESULTS: A substantial decrease in the
      size of the cyst was observed in the 3 months after treatment. Nine months after
      treatment, the shrunken cyst had a volume of only 0.5 ml, and the patient was
      asymptomatic. Twenty-one months after the procedure, the findings were consistent
      with those at 9 months of follow-up. CONCLUSION: Percutaneous treatment of
      orbital hydatid cysts, which is more satisfactory to both the patient and the
      physician, may be a safe and effective alternative to surgical extirpation.

PMID- 9645732
TI  - Pneumo-orbital cyst after orbital fracture repair.
AB  - PURPOSE: To report a case of a respiratory epithelial-lined, air-filled orbital
      cyst as a late complication of orbital fracture repair. METHOD: Case report.
      RESULTS: Recurrent episodes of diplopia and hyperophthalmia developed secondary
      to pneumatic inflation of a respiratory epithelial-lined orbital cyst 6 months
      after orbital fracture repair. This cyst remained in communication with an
      ethmoidal air cell and became inflated during pressurization of the ethmoid
      sinus. Removal of the cyst and orbital implant was curative. CONCLUSION: Air
      filled, respiratory epithelial-lined orbital cyst is a rare cause of episodic
      diplopia and globe displacement after orbital trauma.

PMID- 9645733
TI  - Vascular compression of the oculomotor nerve disclosed by thin-slice magnetic
      resonance imaging.
AB  - PURPOSE: To describe the thin-slice magnetic resonance imaging features of
      vascular compressive oculomotor nerve paresis. METHODS: We performed thin-slice
      (2 mm thick) magnetic resonance imaging of the brainstem in a 74-year-old woman
      with right partial oculomotor nerve paresis using spoiled gradient recalled
      acquisition in the steady state. RESULTS: Thin-slice magnetic resonance images
      disclosed that the right oculomotor nerve was compressed and dislocated
      superiorly and laterally by the tortuous basilar artery. No other abnormalities
      were observed. CONCLUSION: This is the first case report of vascular compressive
      oculomotor nerve paresis disclosed by thin-slice magnetic resonance imaging.

PMID- 9645734
TI  - Severe vision loss and neovascular glaucoma complicating superior ophthalmic vein
      approach to carotid-cavernous sinus fistula.

PMID- 9645735
TI  - Bowel permeability is improved in Crohn's disease after ileocolectomy.
AB  - PURPOSE: Numerous investigators have shown increased bowel permeability in
      patients with Crohn's disease. It is unclear whether this is a precondition
      affecting the entire intestine or a consequence of the inflammation and,
      therefore, only affecting the diseased bowel. The present study tested the
      hypothesis that resection of diseased bowel in patients with ileocolonic Crohn's
      disease would correct abnormalities in bowel permeability. METHODS: Ten patients
      (5 females; mean age, 33 +/- 2 years) with ileocolonic Crohn's disease who
      underwent elective ileocolic resections had bowel permeability measured
      preoperatively and postoperatively by the relative urinary clearance of orally
      consumed lactulose and rhamnose. RESULTS: Mean preoperative bowel permeability in
      patients with Crohn's disease was significantly elevated relative to healthy
      volunteers (0.172 +/- 0.04 vs. 0.046 +/- 0.01; P < 0.05, unpaired t-test). After
      ileocolectomy, bowel permeability decreased in patients with Crohn's disease and
      reached a normal range by postoperative day 30. CONCLUSIONS: Bowel permeability
      is increased in patients with ileocolic Crohn's disease because of the presence
      of diseased bowel and decreases to a normal range in these patients after
      resection of gross intestinal disease. This suggests that bowel permeability may
      be a quantitative and clinically effective method with which to assess the
      presence and severity of diseased bowel in patients with Crohn's disease.

PMID- 9645736
TI  - Functional results after perineal complications of ileal pouch-anal anastomosis.
AB  - PURPOSE: This study investigated the functional significance of perineal
      complications after ileal pouch-anal anastomosis. METHODS: Review of a
      prospective registry of 628 patients was undertaken. Bowel function was assessed
      by detailed functional questionnaire. Statistical analyses were performed using
      chi-squared and Fisher's exact probability tests. RESULTS: Of 628 patients, 153
      (24.4 percent) had 171 perineal complications. The 277 control patients had no
      complications. Complications included 66 (10.5 percent) anastomotic strictures,
      28 (4.5 percent) anastomotic separations, 36 (5.7 percent) pouch fistulas, 41
      (6.5 percent) episodes of pelvic sepsis, and 18 (2.9 percent) patients with
      multiple complications. After these complications were addressed, the pouch
      failure rate was low (10 percent); in 90 percent of patients, the pouch could be
      salvaged. Most pouch failures were the result of pouch fistulas, and most
      occurred in patients ultimately diagnosed with Crohn's disease. Functional
      results after cure of these perineal complications revealed no significant
      functional differences between control patients and those cured of anastomotic
      separations, anastomotic strictures, and pouch fistulas. Only a few minor
      differences were demonstrated in function after an episode of pelvic sepsis. The
      major deterioration in function occurred after treatment for multiple perineal
      complications. CONCLUSIONS: An appreciable number of perineal complications occur
      after ileal pouch-anal anastomosis. Pouch-perineal fistulas are associated with
      the highest pouch failure rate. The majority of these fistulas occur in patients
      ultimately diagnosed with Crohn's disease or indeterminate colitis. Although
      there is no substitute for good technique and sound clinical judgment in the
      success of ileal pouch-anal anastomosis, if perineal complications are
      successfully treated, functional outcome is equivalent to that in patients
      without perineal complications.

PMID- 9645737
TI  - Urinary retention after operations for benign anorectal diseases.
AB  - PURPOSE: This study was undertaken to determine the incidence and risk factors
      for urinary retention after operations for benign anorectal diseases. METHODS: We
      reviewed 1,026 consecutive operations for benign anorectal diseases from 1989 to
      1994. Risk factor analysis was done for patients undergoing hemorrhoidectomy
      (Group I) and other procedures (Group II) using logistic regression analysis.
      RESULTS: The number of procedures and urinary retention rate was as follows: 344
      (34 percent) hemorrhoidectomies, 159 (2 percent) fistulotomies, 95 (5 percent)
      incision/drainage, 247 (4 percent) lateral internal sphincterotomy, 181 (17
      percent) combinations of the above four procedures, and overall 1,026 (16
      percent). In Group I, four-quadrant excision (odds ratio, 3.3; P = 0.0004), three
      quadrant excision (odds ratio, 2.4; P = 0.003), morphine equivalents >33 (odds
      ratio, 1.8; P = 0.01), and male gender (odds ratio, 1.7; P = 0.02) were
      independent risk factors. In Group II, more than one operation (odds ratio, 3.0;
      P = 0.004), older age (odds ratio, 3.1; P = 0.005), intraoperative fluids (odds
      ratio, 2.6; P = 0.03), and postoperative fluids (odds ratio, 2.7; P = 0.02) were
      independent risk factors. Urinary obstructive symptoms for both groups and
      perioperative fluids for Group I were NOT independent risk factors. Hospital stay
      was prolonged significantly in patients with urinary retention (P = 0.0001).
      CONCLUSIONS: Urinary retention is a common postoperative complication that
      increases hospital stay. It is most common after hemorrhoidectomy. Disease
      severity (quadrants excised and analgesia requirement for Group I and number of
      operations for Group II) is an important risk factor for both groups studied.
      Older age in Group I and perioperative fluid in Group II may be important risk
      factors.

PMID- 9645738
TI  - Perineal body measurement improves evaluation of anterior sphincter lesions
      during endoanal ultrasonography.
AB  - Endoanal ultrasonography has become an important tool in the evaluation of
      patients with anal incontinence. However, the extent of anterior defects is
      sometimes difficult to quantitate during endoanal ultrasonography. PURPOSE: This
      study was designed to evaluate perineal body measurement during endoanal
      ultrasonography in assessing patients with obstetric anal sphincter injuries.
      METHODS: Forty-two patients with anal incontinence because of obstetric sphincter
      injuries and 13 asymptomatic subjects were investigated with endoanal
      ultrasonography. Sphincter muscle thickness, sphincter defects, and perineal body
      were measured. Perineal body measurement was performed by inserting a finger,
      held gently against the posterior vaginal wall, into the vagina and measuring the
      distance between the inner surface of the internal sphincter and the
      ultrasonographic reflection of the finger. RESULTS: All patients had anterior
      sphincter lesions of varying extent. Mean size of internal sphincter lesions was
      146 degrees, and mean size of external sphincter lesions was 107 degrees (P <
      0.001). Perineal body measurement was performed without difficulty in all
      patients and subjects. Perineal body measurement (mean +/- standard deviation)
      was 6 +/- 2 mm in patients and 12 +/- 3 mm in asymptomatic subjects (P < 0.001).
      Ninety-three percent of patients had perineal body measurement < or = 10 mm, and
      70 percent of asymptomatic subjects had perineal body measurement > 10 mm.
      Digital delineation of the perineal body during endoanal ultrasonography improved
      the visualization of sphincter lesions in 74 percent of patients. CONCLUSIONS:
      Digital delineation of the perineal body during endoanal ultrasonography improved
      the visualization of sphincter lesions in the majority of patients. Perineal body
      measurement is performed without difficulty and is a good predictor of anterior
      sphincter lesions. Use of this technique improves visualization of sphincter
      lesions.

PMID- 9645739
TI  - Value of postoperative surveillance after radical surgery for colorectal cancer:
      results of a cohort study.
AB  - PURPOSE: Early detection of recurrence after curative resection for primary
      colorectal cancer should improve patients' prognosis. However, the usefulness of
      postoperative surveillance programs has not been clarified yet. The present
      cohort study was aimed at assessing the effectiveness of systematic follow-up in
      patients with colorectal cancer who were operated on for cure, regarding both
      rate of tumor recurrence amenable to curative-intent surgery and rate of
      survival. METHODS: One hundred ninety-nine colorectal cancer patients who
      underwent radical primary surgery were followed according a well-defined
      postoperative surveillance program, which consisted of laboratory studies
      (including serum carcinoembryonic antigen assay) every three months, physical
      examination and abdominal ultrasound or computed tomography every six months, and
      chest radiograph and total colonoscopy once per year. Cohorts were defined
      according to patients' compliance with the proposed follow-up program. A
      multivariate regression model was constructed to predict survival. RESULTS: One
      hundred forty patients were considered to be compliant with the surveillance
      program, whereas the remaining 59 patients occasionally attended follow-up
      investigations or did not comply at all. Although there were no differences in
      the overall recurrence rate (38 vs. 41 percent; P = 0.52), curative-intent
      reoperation was possible in 18 patients (34 percent) of those with tumor
      recurrence in the compliant cohort but in only 3 patients (12 percent) in the
      noncompliant cohort (P = 0.05). Similarly, the probability of survival was higher
      in the compliant cohort, both regarding overall (63 vs. 37 percent at 5 years; P
      < 0.001) and cancer-related (69 vs. 49 percent at 5 years; P < 0.02) rates. Cox
      regression analysis disclosed that only a more advanced TNM stage (odds ratio,
      8.17; 95 percent confidence interval, 1.13-59.29) and noncompliance with the
      postoperative surveillance program (odds ratio, 2.32; 95 percent confidence
      interval, 1.50-3.60) had an independent negative impact on survival. CONCLUSION:
      Systematic postoperative surveillance in patients with colorectal cancer who were
      operated on for cure increases both the rate of tumor recurrence amenable to
      curative-intent surgery and rate of survival.

PMID- 9645740
TI  - Cost-effectiveness of dynamic graciloplasty in patients with fecal incontinence.
AB  - PURPOSE: This study evaluates the cost-effectiveness of dynamic graciloplasty for
      intractable fecal incontinence. PATIENTS AND METHODS: The costs and effects of
      dynamic graciloplasty were measured in a prospective, longitudinal study and in a
      clinical trial. Forty-three patients with intractable fecal incontinence were
      evaluated before and after dynamic graciloplasty. Costs were obtained from the
      hospital information system and from patient-oriented questionnaires. We compared
      the costs of a dynamic graciloplasty with the costs of a colostomy. Colostomy
      costs were evaluated using a group of seven patients who had a stoma in place for
      incontinence for several years. Sensitivity analyses were included. RESULTS:
      Total direct costs of lifelong dynamic graciloplasty were $31,733 (United States
      dollars), costs of lifelong conventional treatment were $12,180 (United States),
      and costs of colostomy, including lifelong stoma care, were $71,576 (United
      States). The clinical success rate of dynamic graciloplasty was 74 percent.
      Quality of life after successful dynamic graciloplasty was better than with
      conventional treatment. CONCLUSION: We found that dynamic graciloplasty was more
      expensive than conventional treatment but resulted in a significantly higher
      quality of life. Stoma treatment was the least attractive alternative regarding
      both costs and effects. The Dutch Health Insurance Executive Board recommended
      reimbursement for the dynamic graciloplasty procedure.

PMID- 9645741
TI  - Which physiologic tests are useful in patients with constipation?
AB  - PURPOSE: Physiologic tests such as manometry, colonic transit times, balloon
      compliance, defecography, pudendal nerve latency, and electromyography are used
      to evaluate patients with severe constipation. Patients referred because of
      severe constipation between 1991 and 1996 were studied to examine the role that
      physiologic testing played in making a diagnosis and directing treatment.
      METHODS: Of 139 patients referred for severe idiopathic constipation, physiologic
      testing was recommended in 127, and 104 patients underwent the studies. The
      pretesting impression was noted, and test results were evaluated to determine
      diagnostic accuracy. If a specific initial impression was documented, tests were
      classified as refuting it, confirming it or confirming and adding significant
      information. If there was no clear pretest impression, tests were evaluated for
      their ability to indicate a diagnosis. The patient's history also was evaluated
      to determine what information was most useful in making a diagnosis. Historical
      features including duration of constipation, symptoms consistent with outlet
      obstruction or dysmotility, age, associated urinary incontinence, and prior
      hysterectomy were analyzed. Data were collected prospectively, then reviewed by
      an independent observer. RESULTS: Ninety-eight study patients remained after 29
      were excluded who did not undergo the recommended studies (19) or because no
      initial impression was documented (10). In 43 patients (44 percent), testing did
      not provide additional useful information. In 8 patients, testing confirmed the
      initial impression and added information impacting the treatment plan. Test
      results clearly refuted the initial impression in only one patient. In 46 (47
      percent) patients the initial impression was uncertain, and in 43 (94 percent) of
      these, testing aided in making the diagnosis. In three cases, the diagnosis
      remained uncertain after testing. Prior hysterectomy (P = 0.003), urinary
      incontinence (P < 0.001), and symptoms of pelvic outlet obstruction (P = 0.03)
      were associated with a high incidence of rectocele. Defecography and transit
      times were the most useful tests. Surprisingly, symptoms of outlet obstruction or
      dysmotility did not show an overall correlation with transit times. CONCLUSIONS:
      In one-half of these patients with severe constipation, physiologic testing added
      significant information, leading to a specific diagnosis. Pretesting history and
      symptoms did not predict which patients were most likely to benefit from these
      studies.

PMID- 9645742
TI  - Long-term functional evaluation of straight coloanal anastomosis and colonic J
      pouch: is the functional superiority of colonic J-pouch sustained?
AB  - AIM: This study was designed to analyze the functional and clinical outcomes of
      straight coloanal anastomosis compared with colonic J-pouch performed after low
      anterior resection. MATERIALS AND METHODS: Between September 1989 and June 1996,
      all patients who underwent low anterior resection with anastomosis less than 4 cm
      from the dentate line were classified into two groups based on the restoration of
      intestinal continuity: "straight" coloanal anastomosis (n = 39) or colonic J
      pouch (n = 44). Both groups were assessed according to the level of anastomosis,
      anastomotic complications (stricture, leak, pelvic abscess), age, and gender. For
      comparison of functional outcome, daily bowel movements, tenesmus, urgency,
      incontinence score (range, 0-20), and anorectal manometric findings were
      evaluated preoperatively and at six months, and one and two years after surgery.
      RESULTS: There were no significant differences between the groups relative to
      age: (coloanal anastomosis, 66.3 +/- 10.1 (range, 46-86), vs. colonic J-pouch,
      64.9 +/- 13.2 (range, 39-88) years); gender (females): (coloanal anastomosis,
      46.2 percent vs. colonic J-pouch; 38.6 percent); diagnosis: (rectal carcinoma:
      coloanal anastomosis, 84.6 percent, vs. colonic J-pouch, 77.3 percent);
      preoperative incontinence score (coloanal anastomosis, 1.5 +/- 4.6, vs. colonic J
      pouch, 1.1 +/- 4); bowel movements: (coloanal anastomosis, 2.1 +/- 2.3, vs.
      colonic J-pouch, 2.1 +/- 1.9/day); level of anastomosis: (coloanal anastomosis,
      1.8 +/- 1.3, vs. colonic J-pouch, 1.5 +/- 1.3 cm from the dentate line); history
      of perioperative radiation therapy: (coloanal anastomosis, 15.4 percent, vs.
      colonic J-pouch, 20.5 percent); or manometric findings. There was also no
      significant difference in postoperative mortality: (coloanal anastomosis, 5.1
      percent, vs. colonic J-pouch, 2.3 percent); or anastomotic complications:
      (coloanal anastomosis, 7/39 (17.9 percent), vs. colonic J-pouch, 2/44 (4.5
      percent) P = 0.08); strictures: (10.3 vs. 0 percent); leaks: (5.1 vs. 2.3
      percent); bleeding: (2.6 vs. 0 percent); rectovaginal fistula: (0 vs. 2.3
      percent). Also, in the colonic J-pouch group, two patients developed pouchitis,
      and one patient experienced difficult evacuation one year after surgery. There
      was a statistically significant better function judged by less frequent bowel
      movements (4 +/- 2 vs. 2.4 +/- 1.3/day; P < 0.005) and urgency (36.7 vs. 7.7
      percent; P < 0.05), incontinence score (2.2 +/- 3.7 vs. 0.8 +/- 1.6; P < 0.05) up
      to one year after surgery. At two years, the coloanal anastomosis group did not
      show statistical improvement in functional results compared with one year
      postoperatively. Rectal compliance in manometric findings was significantly
      increased in the coloanal anastomosis group at one year after surgery (12.4 +/-
      12.6 vs. 4.2 +/- 1.5 ml/mmHg; P < 0.05). However, these differences were less
      profound after two years. CONCLUSION: The functional superiority of the colonic J
      pouch was greatest at one year after surgery. By two years, adaptation of the
      "straight" coloanal anastomosis yielded similar functional results. However, the
      almost fourfold reduction in anastomotic complications in the colonic J-pouch
      group reveals a second potential advantage of this technique.

PMID- 9645743
TI  - Selective expression of carcinoembryonic antigen promoter in cancer cell lines:
      targeting strategy for gene therapy in colorectal cancer.
AB  - PURPOSE: This study was designed to characterize the mechanisms regulating the
      expression of the human carcinoembryonic antigen promoter (pCEA), in terms of
      tissue-specific targeting for gene therapy. The promoter was subcloned to a
      luciferase reporter gene (pCEA/Luc) in our laboratory and compared with a virally
      controlled luciferase vector (pSV40/Luc). METHODS: Four human cancer cell lines
      (HeLa, SW480, Caco2, and SW1116) were transfected with either pCEA/Luc or
      pSV40/Luc. Cells were treated with interferon-gamma and assayed at 72 hours after
      treatment. Carcinoembryonic antigen level was measured by enzyme immunoassay.
      Luciferase expression was measured at 48 hours and one week after transfection by
      luminometry. RESULTS: Luciferase activity after transfection with pCEA/Luc was
      higher in CEA-positive cells than in CEA-negative cells (P < 0.0001). pCEA/Luc
      demonstrated higher activity than pSV40/Luc in CEA-positive cells (P < 0.0001),
      but not in CEA-negative cells. In Caco2 cells, which before confluence are CEA
      negative, luciferase expression increased on reaching confluence (P < 0.0001).
      Well to moderately differentiated cells responded to the interferon-gamma
      treatment, but the increase in CEA secretion did not correspond to an increase in
      pCEA/Luc expression. CONCLUSIONS: The expression of pCEA correlates well with the
      CEA production by the specific cell line offering a potential tissue-specific
      targeting strategy for colon cancer gene therapy. Furthermore, the tissue
      specific CEA promoter has a higher and more persistent activity in CEA-positive
      human cancer cells than a viral promoter. The lack of response to interferon
      gamma treatment suggests a different mechanism of action for interferon-gamma
      other than directly interacting with the promoter.

PMID- 9645744
TI  - DCC protein as a predictor of distant metastases after curative surgery for
      rectal cancer.
AB  - PURPOSE: The aim of this study was to determine the value of DCC (deleted in
      colorectal cancer) protein for predicting metachronous distant metastases after
      curative surgery for rectal cancer. The DCC protein--for which a gene has been
      located on chromosome 18q--has recently been reported to have a prognostic value
      in colorectal cancer. This finding might have implications for treatment of
      International Union Against Cancer Stage II rectal carcinoma, in which distant
      metastases will develop in 14 percent of patients despite optimal surgery.
      METHODS: Paraffin-embedded tissues from 85 patients who developed distant
      metastases, but no local recurrence, after curative surgery for rectal cancer
      were matched with 85 samples from patients who remained disease-free. Matching
      criteria were tumor stage, age, gender, and date of surgery. Expression of DCC
      protein was assessed using immunohistochemistry. End points of follow-up were
      recurrence of disease and death. Mean follow-up was 9.6 years. No patient
      received either local or systemic adjuvant therapy. RESULTS: The DCC protein was
      found to be expressed in 64.9 percent of tumor samples. Nonexpression of DCC
      protein had an negative influence on survival (P = 0.03). For all tumor stages
      together, sensitivity of the test for subsequent occurrence of distant metastases
      was 42 percent and specificity was 71 percent. In Stage II cancers, the positive
      predictive value was 19 percent, and the negative predictive value was 88
      percent. CONCLUSIONS: Our results confirm that DCC protein is a useful prognostic
      marker in patients with rectal carcinomas, but the positive predictive value of
      DCC protein for occurrence of metachronous metastases does not appear to be
      sufficient to justify adjuvant therapeutic measures in Stage II rectal cancer.

PMID- 9645745
TI  - Limitation of endorectal ultrasonography: what does a low lesion more than 5 mm
      in size correspond to histologically?
AB  - PURPOSE: The accuracy of diagnosis of metastatic lymph nodes for rectal carcinoma
      has not improved. A low echoic lesion more than 5 mm in size detected by
      endorectal ultrasonography is preoperatively assessed as a metastatic lymph node.
      What does a low echoic lesion more than 5 mm in size correspond to
      histologically? METHODS: Forty-seven patients with lower rectal carcinoma (Term
      I, 1986-1990) and 48 patients with lower rectal carcinoma (Term II, 1991-1995)
      undergoing endorectal ultrasonography were reviewed. Surgically resected rectal
      specimens from 40 patients with rectal carcinoma underwent ultrasonography. Low
      echoic lesions more than 5 mm in size were taken from resected specimens and were
      stained with hematoxylin, followed by histologic examination. RESULTS: The
      accuracy of diagnosis of metastatic lymph nodes of Term II was not higher than
      that of Term I. Twenty-five low echoic lesions were detected by ultrasonography
      using 40 resected specimens. Seventeen of these 25 lesions (68 percent) were
      histologically confirmed to be metastatic lymph nodes. One of 25 (4 percent) was
      found to be lymphadenitis with no metastasis. Among the 25 lesions, 5 (20
      percent) were histologically confirmed to be tumor deposits, 2 (8 percent) fatty
      tissue, and 22 (88 percent) carcinoma. CONCLUSIONS: Low echoic lesions were
      histologically confirmed to be tumor deposits (20 percent) and metastatic lymph
      nodes (68 percent). Although these data show deficiencies and limitations of the
      accuracy of endorectal ultrasonography, they compare favorably with other series,
      and no other current technology can show similar accuracy.

PMID- 9645746
TI  - Incidence of DNA replication errors in patients with multiple primary cancers.
AB  - PURPOSE: Multiple primary cancers are a feature of hereditary nonpolyposis
      colorectal cancer in which defects in DNA repair mechanisms result in
      accumulation of replication errors within tumor DNA. We assessed replication
      error incidence in multiple primary cancer patients who may have similar genetic
      defects. METHODS: DNA was obtained from 69 patients from the Yorkshire region who
      had developed colorectal cancer and one other primary tumor from the hereditary
      nonpolyposis colorectal cancer tumor spectrum (28 colorectal, 12 stomach, 15
      ovary, and 14 uterus). DNA was also obtained from 86 sporadic, single primary
      cancer patients attending a colorectal cancer clinic. Replication error status
      was assessed at five microsatellite loci using fluorescent polymerase chain
      reaction and computer-assisted analysis. RESULTS: The replication error phenotype
      was observed in 7 of 86 (8 percent) of the sporadic single primary patients. This
      compared with 23 of 69 (33 percent) of the multiple primary group (P < 0.001).
      Replication error was also observed more frequently in each subgroup. Even
      excluding patients from families meeting the Amsterdam criteria (likely to be
      hereditary nonpolyposis colorectal cancer and have the replication error
      phenotype), this increased frequency remained in both the multiple primary group
      (P < 0.005) and multiple colorectal and colorectal/uterine subgroups (P < 0.001).
      CONCLUSIONS: Results suggest that genetic instability plays an important role in
      development of multiple primary cancers, particularly from certain cancer
      subsets. Testing for replication errors may be an appropriate way of identifying
      individuals at risk of multiple primary cancers.

PMID- 9645747
TI  - Relationship between serum ELAM-1 and metastasis among patients with colon
      cancer.
AB  - PURPOSE: We studied serum ELAM-1 levels in colon cancer patients. METHODS AND
      RESULTS: Serum ELAM-1 levels were significantly higher in 52 patients with colon
      cancer (mean +/- standard deviation, 69.3 +/- 28.6 U/ml) compared with 32 healthy
      volunteers (36.5 +/- 11.9 U/ml; P < 0.001). The mean serum ELAM-1 level in
      patients with metastatic tumors was significantly greater than that of patients
      with nonmetastatic tumors. Sensitivity and specificity of serum ELAM-1 elevation
      in detecting metastasis was 75 and 87.5 percent, respectively. Those of
      carcinoembryonic antigen and carbohydrate antigen 19-9 elevations were 71.4 and
      62.5 percent and 35.7 and 91.7 percent, respectively. Twenty-five (89.3 percent)
      of 28 metastatic tumors showed either serum ELAM-1 or carcinoembryonic antigen
      elevation. There were weak but significant correlations found between serum ELAM
      1 and carcinoembryonic antigen or carbohydrate antigen 19-9 levels. Moreover,
      serum ELAM-1 increased before detecting the recurrence by imaging in five of
      seven recurrent colon cancer patients. CONCLUSION: These findings suggest that
      serum ELAM-1 could be a useful tumor marker for colon cancer, especially in
      synchronous and metaclonous metastasis.

PMID- 9645748
TI  - Management of pilonidal sinus with the Limberg flap.
AB  - PURPOSE: The aim of this study was to demonstrate the advantages of rhombic
      excision and Limberg flap closure in the treatment of pilonidal sinus disease.
      METHODS: We treated 24 patients who had chronic pilonidal sinus disease with
      rhomboid excision and Limberg flap closure. RESULTS: All patients were followed
      up for a period of 27 months. Mean hospital stay was 4.1 days, and mean time
      until return to work was 17.5 days. There was no surgical wound infection.
      Complication rate was 12.5 percent. During the follow-up period, no recurrence
      was found. CONCLUSION: Because other treatment methods carry a significant
      failure rate, this technique is an effective alternative in the treatment of
      pilonidal sinus disease.

PMID- 9645750
TI  - Rectal sleeve advancement: repair of rectovaginal fistula associated with
      anorectal stricture in Crohn's disease.
AB  - Successful repair of rectovaginal fistula in patients with Crohn's disease has
      been reported when these patients have a normal appearing rectum. We report the
      performance of stricturectomy in conjunction with circumferential rectal sleeve
      advancement for patients who have a rectovaginal fistula arising from an
      anorectal stricture secondary to Crohn's disease. This technique provides for
      repair of rectovaginal fistula and correction of the anal stricture and maintains
      continence.

PMID- 9645749
TI  - Pelvic floor function in patients with clinically complete spinal cord injury and
      its relation to constipation.
AB  - PURPOSE: Constipation is a common problem in patients with spinal cord injury.
      The aim of this study is to analyze the role of pelvic floor dysfunction in the
      development of constipation. METHODS: Twenty-five patients with clinically
      complete supraconal spinal cord injury were studied by means of colonic transit
      time, anal manometry, electrophysiologic testing, and sensory-evoked potentials.
      RESULTS: Sixteen patients had prolonged total and segmental colonic transit times
      (Group C), and nine patients had normal colonic transit times (Group NC). Basal
      pressure and anal pressure during coughing, Valsalva's maneuver, and rectal
      distention were diminished in all patients, but no differences were observed
      between Group C and Group NC. Rectal sensation was preserved in eight patients,
      but this was not related to the absence of constipation. In seven of these eight
      patients, somatosensory-evoked potentials could be recorded, which indicated an
      incomplete cord lesion. Synergic relaxation of the pelvic floor during straining
      was never observed; dyssynergia was seen in ten (7 in Group C and 3 in Group NC;
      P = not significant) patients. Associated peripheral nerve damage was present in
      40 percent of patients but did not predispose these patients to constipation.
      CONCLUSIONS: Loss of rectal sensation, dyssynergic pelvic floor contraction
      during straining, associated peripheral nerve damage, and insufficient rise of
      intraabdominal pressure could not be held responsible for constipation as a
      result of spinal cord injury. A prolongation of the colonic transit time is the
      most important mechanism, and therapy should be directed toward it.

PMID- 9645751
TI  - Double-gracilis anorectal neosphincter: technique of reconstruction after
      necrosis of the distal part of the muscles.
AB  - PURPOSE: The aim of the present study is to demonstrate further reconstruction of
      a double-gracilis anorectal neosphincter that had been destroyed because of a
      severe postoperative perineal infection, with necrosis of the distal part of the
      muscles. METHOD: Each residual gracilis muscle was split longitudinally into two
      branches, which surrounded the neorectum, one posteriorly and the other one
      anteriorly, so as to perform a perineorectal double sling. RESULT: Owing to a
      poor functional result, continence was achieved only by the support of an
      implantable pulse generator. CONCLUSION: This technique seemed to permit the
      optimum use of the contractile potential of the residual gracilis muscles, which
      did not show evidence of defunction-related or ischemia-related fibrosis.

PMID- 9645752
TI  - Passage of a large bowel cast caused by acute ischemia: report of two cases.
AB  - PURPOSE: We report two cases of spontaneous anal passage of a large bowel 'cast'
      caused by acute ischemic injury. METHODS: Clinical, laboratory, endoscopic, and
      pathologic features were reviewed, and the literature was searched for similar
      cases. RESULTS: An 85-year-old male who had undergone aortic surgery recovered
      from rectosigmoid ischemia after undergoing a descending colostomy. A 74-year-old
      male with severe pancreatitis developed a postischemic sigmoid stricture but did
      not have operative treatment before death of pneumonia three months after the
      episode. A literature review revealed six cases of passage of a large bowel cast.
      In the eight total patients, infarcted muscularis propria was found in seven
      specimens, five patients had a diversion procedure, and seven survived.
      CONCLUSION: Passage of a large bowel cast is an extraordinary complication of
      ischemia that often requires diverting surgery, and most patients survive the
      ischemic injury.

PMID- 9645753
TI  - A father and son with Turcot's syndrome: evidence for autosomal dominant
      inheritance: report of two cases.
AB  - Typical Turcot's syndrome is characterized by the association of a brain glioma
      together with multiple colonic polyposis, in which the number of polypoid lesions
      is small and the association of colonic cancer occurs at a younger age than in
      familial adenomatous polyposis. We describe a family in which both the father and
      his son presented with typical Turcot's syndrome without parental consanguinity.
      This is the first report of a family that is considered to follow an autosomal
      dominant inheritance. After reviewing 25 documented cases in which the average
      age of death was 20.3 years old, it was learned that the major cause of death was
      brain tumor (76 percent) and the minor cause was colon cancer (16 percent).
      Patients were very young and, therefore, unlikely to have produced a child before
      their death. These facts seem to support the theory that Turcot's syndrome is an
      autosomal dominant disorder.

PMID- 9645754
TI  - Endosonographic image of a retrorectal bowel duplication: report of a case.
AB  - PURPOSE: Endosonographic image and surgical therapy of a retrorectal bowel
      duplication are described. METHODS, RESULTS, AND CONCLUSIONS: Compared with
      standard investigations, the most accurate information about a retrorectal mass
      in a 35-year-old woman could be obtained by means of endorectal ultrasound.
      Guided by endorectal ultrasound, the mass was excised using a transanal
      transrectal approach, and Kraske's operation could be avoided. Additionally,
      histopathologic analysis of this rare disease is presented.

PMID- 9645755
TI  - Induction of acute inflammation in vivo by staphylococcal superantigens I:
      Leukocyte recruitment occurs independently of T lymphocytes and major
      histocompatibility complex Class II molecules.
AB  - Studies in our laboratory and others have recently shown that staphylococcal
      enterotoxin-derived superantigens stimulate proinflammatory cytokine gene
      expression in vitro. We have therefore investigated the ability of superantigens
      to induce leukocyte accumulation at extravascular sites in vivo using the
      subcutaneous air pouch model. Injection of staphylococcal enterotoxin A (SEA)
      induced a significant accumulation of leukocytes over basal levels in a time- and
      dose-dependent manner. It was also shown that superantigens are capable of
      inducing this response in mice depleted of CD4 T cells, as well as in severe
      combined immune-deficient and nude mice. These observations suggest that
      superantigens are capable of inducing leukocyte accumulation independently of the
      presence of T lymphocytes. Experiments were also conducted using mutant SEAs that
      have a reduced binding affinity for major histocompatibility complex (MHC) Class
      II molecules, as well as using MHC Class II-deficient mice. The results of these
      experiments indicated that MHC Class II molecules are not required for the
      observed effect of superantigens in vivo. Taken together, these results indicate,
      first, that bacterial superantigens promote inflammation in subcutaneous tissue
      in vivo and, second, the potential existence of a novel receptor for
      superantigens that mediates this subcutaneous inflammatory response.

PMID- 9645756
TI  - Development of porous defects in plasma membranes of adenosine triphosphate
      depleted Madin-Darby canine kidney cells and its inhibition by glycine.
AB  - Studies during the past decade have led to the recognition of a fundamental,
      widely expressed mechanism of structural damage in energy-deprived cells, which
      is suppressed by physiologic levels of glycine and is independent of Ca2+
      availability or alterations of cytosolic free Ca2+. To gain insight into this
      process, Madin-Darby canine kidney (MDCK) cells were depleted of adenosine
      triphosphate (ATP) by a mitochondrial uncoupler in glucose-free medium, and
      intracellular free Ca2+ was clamped at 100 nM to avoid calcium cytotoxicity.
      Although the ATP-depleted cells swelled and blebbed and their plasma membranes
      appeared to be under tension, they nevertheless became permeable to
      macromolecules. The plasma membranes of these cells retained structural
      continuity, as determined by morphologic observations, and confocal microscopy of
      a plasma membrane protein label (Biotin: Ultra Avidin-Texas Red) and a lipid
      label (NBD-sphingomyelin). Using fluoresceinated dextrans of graded molecular
      size, membrane permselectivity was examined noninvasively by confocal microscopy.
      Measured as inside/outside ratios of fluorescence intensity, the permeability
      indices showed progressively greater restriction to diffusion of increasingly
      larger dextran molecules across plasma membranes, with sharp break-points between
      70,000 and 145,000 daltons (d). The results indicated that the membranes behaved
      as if they were perforated by water-filled channels or "pores," with size
      exclusion limits of molecular dimensions. The membrane defects evolved from small
      pores permeable only to propidium iodide (668 d) and the smallest dextran (4,000
      d), before enlarging with time to become permeable to larger dextrans. Inclusion
      of glycine during ATP depletion did not affect cell swelling or blebbing but
      completely prevented the development of permeability defects. Treatment of cells
      before ATP depletion with a membrane-impermeant homobifunctional "nearest
      neighbor" cross-linking agent, 3,3' dithiobis(sulfosuccinimidylpropionate),
      suppressed the development of permeability defects, even in the absence of
      glycine. These observations suggest that the cellular abnormality that is
      suppressed by glycine involves rearrangement of plasma membrane proteins to form
      water-filled pores large enough to leak macromolecules.

PMID- 9645757
TI  - Status of deleted in colorectal cancer gene expression correlates with
      neuroblastoma metastasis.
AB  - Neuroblastoma is an embryonal tumor of neural crest origin noted for its
      heterogeneity at the clinical, histologic, and molecular levels. The deleted in
      colorectal cancer (DCC) protein is an adhesion family molecule of unequivocal
      importance in neural development that has also been implicated in several
      malignancies, including neuroblastoma, through its apparent loss of function.
      Immunohistochemical assessment of the DCC protein was performed on a group of 49
      neuroblastoma specimens and examined in relation to important clinical,
      histologic, and molecular parameters. DCC expression was significantly associated
      with neuroblastoma dissemination as primary tumors from Stage 1 to 3 patients
      (15/20, 75%) more frequently exhibited the DCC protein than those from Stage 4
      patients (5/13, 38%; p = 0.0415). Primary tumors were more frequently DCC
      positive (20/33, 61%) as compared with metastatic deposits (3/16, 19%; p =
      0.0063), and a single case of a paired primary and metastatic deposit
      demonstrated the apparent loss of DCC gene expression with tumor progression. The
      remaining five paired specimens were DCC-negative in both the primary tumor and
      metastatic deposit. No significant association was appreciated between DCC
      expression and patient age, the Shimada histologic classification, or N-Myc
      amplification. These results provide evidence that DCC expression may be lost in
      the course of metastatic spread in a subset of neuroblastomas. Moreover, DCC
      function is implicated in neuroblastoma dissemination in a manner independent of
      N-Myc.

PMID- 9645758
TI  - Oligoclonal T-cell proliferation and interferon-gamma production in
      periprosthetic inflammation.
AB  - Total joint arthroplasty has dramatically changed the treatment options for
      patients with destructive joint disease. The materials used to manufacture
      implants are regarded as biologically inert; accordingly, arthroplasty is a very
      successful intervention for most patients. However, a subset of patients develops
      an inflammatory reaction around the prosthesis, causing implant loosening and
      irreversible bone destruction. To identify mechanisms leading to periprosthetic
      inflammation, the function and composition of macrophages and T cells accumulated
      in the pseudosynovia were examined. Tissue-infiltrating macrophages synthesized a
      spectrum of proinflammatory cytokines including IL-1beta, IL-6, and TGF-beta. T
      cells recruited to the periprosthetic inflammatory lesions were characterized by
      restricted diversity of T-cell receptors and the emergence of dominant clonal
      populations. T cells with identical T-cell receptor sequences, and thus with
      identical antigen specificity, were isolated from anatomically distinct and
      independent regions of the tissue. Transcription of IL-2, IFN-gamma, and, in some
      patients, IL-4 genes in the periprosthetic membrane indicated functional
      activation of infiltrating T cells. Correlation of periprosthetic osteolysis with
      the tissue cytokine pattern demonstrated a relationship between IFN-gamma
      transcription and bone loss. We propose that antigen-recognition events are
      critically involved in the development of periprosthetic inflammation and that
      the functional commitment of T cells recruited to the periprosthetic region
      influences whether periprosthetic inflammation is complicated by bone
      destruction.

PMID- 9645759
TI  - Localization of matrix metalloproteinases-1, -2, and -9 and tissue inhibitor of
      metalloproteinase-2 in interstitial lung diseases.
AB  - In interstitial lung diseases, deposition of extracellular matrix (ECM) in
      alveoli and degradation of ECM lead to pulmonary structural remodeling. The
      changes in ECM and the localization of matrix metalloproteinases (MMPs) and a
      tissue inhibitor of metalloproteinases (TIMP) in the lung tissues of patients
      with bronchiolitis obliterans organizing pneumonia (BOOP) and idiopathic
      pulmonary fibrosis (IPF) were investigated. Immunohistochemical analysis for the
      detection of fibronectin, collagen-I, -III, and -IV, smooth muscle actin, MMP-1
      (interstitial collagenase), -2 (gelatinase A), and -9 (gelatinase B), and TIMP-2,
      and in situ hybridization for the detection of MMP-9 mRNA were performed. Western
      blotting of lung tissue homogenates was performed for MMP-2 and MMP-9. The
      gelatinolytic activities of the homogenates were also determined using gelatin
      zymography. Fibronectin and collagen-I, -III, and -IV were detected in the intra
      alveolar fibrosis in addition to the interstitium of these diseases. MMP-1, MMP
      2, MMP-9, and TIMP-2 were detected in the regenerated epithelial cells covering
      intra-alveolar fibrosis. Myofibroblasts in intra-alveolar fibrosis in BOOP showed
      predominant reaction for MMPs, and they ultrastructurally appeared to be
      phagocytosing collagen fibrils, and those of IPF showed a predominant reaction
      for TIMP-2. New vascularization in intra-alveolar fibrosis was exclusively
      observed in cases of BOOP, and the endothelial cells were positive for MMP-2.
      Western blotting showed the existence of a latent form of MMP-9 and latent and
      active forms of MMP-2, and gelatin zymography revealed that the ratio of
      active/latent forms of MMP-2 in BOOP is significantly larger than that in the
      control lungs. Predominant MMPs in BOOP may constitute the mechanism of
      reversibility of fibrotic changes in this disease. TIMP-2 in myofibroblasts in
      IPF may contribute to the stable ECM deposition and the irreversible pulmonary
      structural remodeling.

PMID- 9645760
TI  - Expression of the 150-kd oxygen-regulated protein in human breast cancer.
AB  - Tumor cells subjected to environmental stress, such as oxygen deprivation
      followed by reoxygenation, redirect biosynthetic pathways to express oxygen
      regulated proteins (ORPs) and heat-shock proteins (HSPs). The 150-kd oxygen
      regulated protein (ORP150) is a novel endoplasmic reticulum-associated
      polypeptide in the HSP70 family. In view of links between expression of HSPs/ORPs
      and tumor properties, especially tumor invasiveness and resistance to therapeutic
      regimens, expression of ORP150 in human breast cancers was examined. Western and
      Northern blotting demonstrated elevated expression of ORP150 in breast cancer,
      regardless of estrogen receptor status, compared with normal breast tissue.
      Immunohistochemical and in situ hybridization techniques revealed that
      infiltrating cancer cells in the stroma expressed ORP150 more strongly than large
      nests of cancer cells. Furthermore, pancreatic and thyroid carcinomas also
      displayed greater ORP150 expression. These results suggest that ORP150 is up
      regulated in tumors and, in breast tumors, may be associated with tumor
      invasiveness.

PMID- 9645761
TI  - Chemotherapy of an experimental Trypanosoma cruzi infection with specific
      immunoglobulin-chlorambucil conjugate.
AB  - Hybrid molecules were constructed with either polyclonal antibodies against
      Trypanosoma cruzi antigens or monoclonal antibody against Trypanosoma brucei
      brucei low-density lipoprotein (LDL)-receptor conjugated with chlorambucil.
      Physical-chemical analysis of the hybrid molecule showed four chlorambucil
      coupling sites in each IgG and a binding constant in the order of 10(4).
      Maintenance of IgG integrity was indicated by its circular dichroism pattern.
      Biologic activity of the hybrid molecule was shown by its inhibitory effect on
      the mobility and proliferation of the parasite. An IgG-chlorambucil conjugate,
      produced with monoclonal antibody anti-T. b. brucei LDL-receptor, led to the
      immobilization of the T. cruzi forms, albeit at a much lesser level than that
      obtained with a mouse polyclonal anti-T. cruzi IgG linked to the drug. Targeting
      experimental T. cruzi infection with a specific IgG-chlorambucil conjugate
      resulted in consistent reduction of parasitemia and mortality, thus showing its
      potential usefulness in controlling the acute form of the disease.

PMID- 9645762
TI  - Detection of transcripts initiated from two viral promoters (Cp and Wp) in
      Epstein-Barr virus-infected nasopharyngeal carcinoma cells and biopsies.
AB  - Different activation of Epstein-Barr virus (EBV) promoters results in distinct
      expression patterns of EBV nuclear antigens (EBNAs) and may further decide the
      role of EBV in the cellular pathogenesis. In EBV-associated nasopharyngeal
      carcinoma (NPC) biopsies, it has generally been believed that Q promoter (Qp)
      initiated EBNA1 is the only EBNA gene to be expressed and that the other two
      viral promoters, Cp and Wp, which can lead to expression of EBNA1-6, are
      inactive. However, the failure to demonstrate the activities of Cp and Wp may
      have been due to the limited sensitivities of detection approaches used. In the
      present article, the EBV promoter usage and gene expression were re-examined in
      both EBV-infected NPC cells in vitro and NPC biopsies in vivo. An NPC cell line
      susceptible to EBV infection in vitro was established by transfection with a
      plasmid expressing a well-known EBV receptor, CR2. The presence of viral DNA and
      EBNA proteins was demonstrated in these EBV-infected cells using PCR and
      anticomplement immunofluorescence assay, respectively. As has been identified in
      NPC biopsies, viral transcripts of Qp-initiated EBNA1, latent membrane protein
      (LMP)1, LMP2A, LMP2B, and BamHI A genes, as well as the EBV-encoded small RNA
      (EBER)1 were detected in these in vitro-infected cells using reverse
      transcription-PCR. Notably, viral transcripts initiated from Cp or Wp were also
      found in the infected cells. Furthermore, Cp- or Wp-initiated transcripts and
      EBNA2 mRNA were detected in some NPC biopsies. Taking advantage of this sensitive
      detection approach, our observation that Cp and Wp may be active in NPC cells
      raises the possibility that EBNA2 to 6, in addition to EBNA1, may play roles in
      the pathogenesis of NPC.

PMID- 9645763
TI  - Mutation of the p53 gene in postradiation sarcoma.
AB  - Radiotherapy is known to cause secondary malignancies in the radiation field;
      postradiation sarcomas (PRS) are one example of such malignancies. Little is
      known about the genetic changes, including p53 gene alterations, that are thought
      to play a role in the tumorigenesis of human PRS. In the present study, p53 gene
      mutations were analyzed on paraffin-embedded specimens from 24 patients with PRS
      (4 men and 20 women) by polymerase chain reaction-single-strand conformation
      polymorphism (PCR-SSCP) followed by direct sequencing. The primary tumors of
      these patients were uterine cervical cancers in 14, breast cancers in 3,
      malignant lymphomas in 2, and others in 5. Total radiation doses ranged from 36
      to 300 Gy (median, 60 Gy). The latent period between completion of radiation
      therapy and development of PRS ranged from 3 to 34 years (median, 10 years).
      Malignant fibrous histiocytoma was the most common PRS, accounting for 12 cases.
      PCR-SSCP revealed the aberrant mobility shifts of bands in 24 cases: 21 shifts in
      exon 5, 18 in exon 7, and 12 in exon 8. Direct sequencing of the SSCP product
      revealed a total of 58 mutations in 21 (88%) of 24 cases: 4 cases had a single
      mutation, 5 had 2 mutations, 5 had 3 mutations, 6 had 4 mutations, and 1 had 5
      mutations. Although 31% of the mutations did not change an amino acid, every
      tumor had at least one mutation that did, which may have provided the selection
      pressure for expansion. The frequency of p53 gene mutation in sporadic soft
      tissue sarcomas was 20%. These findings highlighted the extraordinarily high
      frequency of p53 gene mutations in PRS. G:C to A:T transition at dipyrimidine
      sites was found in 14 (58%) of 24 cases. Collectively, these findings indicate
      that radiation is causative for soft tissue sarcomas via p53 gene mutations.

PMID- 9645764
TI  - The membrane-type-matrix metalloproteinase/matrix metalloproteinase-2/tissue
      inhibitor of metalloproteinase-2 system in periprosthetic connective-tissue
      remodeling in loose total-hip prostheses.
AB  - The aim of the present study was to investigate the proteolytic potential and
      localization of matrix metalloproteinase (MMP)-2 in relation to its regulatory
      protein, membrane-type-MMP (MT1-MMP), and tissue inhibitor of metalloproteinase-2
      (TIMP-2), as well as to clarify an important step in the cascade of
      periprosthetic connective-tissue remodeling in loose total-hip prostheses.
      Immunohistochemical analysis revealed increased expression of MT1-MMP, MMP-2, and
      TIMP-2 in fibroblasts, synovial lining-like cells, and endothelial cells, as well
      as, to some extent, in monocyte/macrophage-like cells in both tissues from the
      bone-implant interface and reactive cellular tissues from regenerating capsules
      in loose hip joints, when compared with control fibrous tissues between bone and
      implants retrieved from unloosened hip joints. In loose hip joints, reverse
      transcription-PCR analysis showed the presence of MT1-MMP, MMP-2, and TIMP-2 mRNA
      in both the bone-implant interface and regenerating capsular tissues. Increased
      protein levels of MMP-2 and TIMP-2 were also demonstrated by an ELISA, and those
      of MT1-MMP were shown by immunoblot analysis. Gelatin-zymographic analysis
      confirmed the presence of both pro- and active forms of MMP-2, which suggested
      the in situ activation of MMP-2 by MT1-MMP in the loose hip joints. Collectively,
      these data suggest that the MT1-MMP/MMP-2/TIMP-2 system participates in the
      extracellular matrix degradation and periprosthetic connective-tissue remodeling
      in loose hip joints, and may thus contribute to the periprosthetic weakening,
      loosening, and osteolysis that can occur around implants.

PMID- 9645765
TI  - Abnormal thymocyte development and generation of autoreactive T cells in mixed
      and cortical thymomas.
AB  - To gain insight into the pathogenesis of thymoma-associated myasthenia gravis,
      thymocyte maturation was investigated in mixed and cortical thymomas by three
      color flow cytometry. Although we detected cells at all recognizable stages, we
      noted an unusual increased percentage of early CD4+/CD3- thymocytes--especially
      in mixed thymoma--and a pronounced decreased percentage of mature CD4+/CD3+ cells
      in cortical thymomas as well. The percentage of CD3+/CD69+ cells that arose after
      positive selection was reduced in both thymoma subtypes compared with control
      thymuses, which suggests differences in the rate or efficiency of positive
      selection particularly in mixed thymomas. Mature T cells in 10 of 11 thymomas
      were not activated in situ as shown by the absence of CD25 expression. After
      stimulation with recombinant human acetylcholine receptor alpha-subunit
      fragments, thymocytes from 8 of 11 thymomas of both subtypes proliferated more
      strongly than those from controls, regardless of whether the donors were
      myasthenic. Responses of residual thymus cells to tetanus toxoid correlated well
      with those of autologous blood T cells, whereas those from the thymomas clearly
      did not--implying minimal colonization of thymomas by mature recirculating T
      cells. In conclusion, our results show that cortical and mixed thymomas exhibited
      differences in thymocyte maturation. Nevertheless, both thymoma subtypes seem to
      contribute to the pathogenesis of paraneoplastic myasthenia gravis by generating
      naive but potentially autoaggressive T cells; in some thymomas, these cells may
      then be actively immunized inside the tumor.

PMID- 9645766
TI  - Interleukin-8 production by polymorphonuclear neutrophils in patients with
      rapidly progressive periodontitis: an amplifying loop of polymorphonuclear
      neutrophil activation.
AB  - Polymorphonuclear neutrophils (PMN) are the most abundant immune cells in
      inflammatory gingival sites of patients with early onset periodontitis, localized
      juvenile periodontitis, and rapidly progressive periodontitis (RPP). In the
      latter, the large number of PMN in connective tissue may explain the marked
      gingival destruction. Because interleukin-8 (IL-8) is a potent PMN
      chemoattractant, we evaluated circulating levels and gingival mRNA expression of
      IL-8. We found high IL-8 plasma levels as well as strong IL-8 mRNA expression in
      both epithelial and connective gingival cells from patients with RPP. Moreover,
      the gingival PMN themselves contained IL-8 mRNA, suggesting an autoamplification
      of PMN recruitment and activation in the gingiva. We also measured the expression
      of adhesion molecules at the PMN surface as well as the oxidative burst in whole
      blood from 14 patients with RPP, using flow cytometry to avoid irrelevant
      stimulations and to analyze single cells. In RPP patients, resting PMN showed
      reduced L-selectin, Lewis x, and sialyl Lewis x antigen expression as well as
      increased H2O2 production. These modifications of PMN adhesion molecule
      expression, together with their increased basal oxidative burst and excessive IL
      8 production, may contribute to the noxious inflammatory reaction, which may in
      turn be autopotentiated by PMN production of IL-8. In addition, PMN showed a lack
      of increased response (H2O2 production) to formyl peptides after ex vivo priming
      with IL-8, possibly owing to IL-8 desensitization that may be involved in the
      increased susceptibility of RPP patients to infection. After appropriate
      treatment of RPP, the reduction in inflammation was associated with a return to
      control levels of both plasma IL-8 and PMN functions, suggesting that these
      features are linked.

PMID- 9645767
TI  - Direct detection of premature protease activation in living pancreatic acinar
      cells.

PMID- 9645768
TI  - Development, progression, and androgen-dependence of prostate tumors in probasin
      large T antigen transgenic mice: a model for prostate cancer.
AB  - Probasin (PB) gene product is prostate-specific, epithelial cell in origin, and
      androgen-regulated. A large 12-kb promoter fragment of the PB gene (LPB) was
      linked to the simian virus 40 (SV40) large T antigen (Tag) deletion mutant (that
      removes the expression of the small t antigen) to deliver consistently high
      levels of transgene expression to the transgenic mouse prostate. Seven male
      founders, their male offspring, and all the male offspring from two female
      founders developed at least prostatic epithelial cell hyperplasia by 10 weeks of
      age, indicating that the incidence of transformation was 100%. Tumorigenesis in
      the LPB-Tag animals progressed in a manner similar to that observed in the human
      prostate. Initially, multifocal proliferating lesions were detected in the
      prostatic epithelium, which continued to progress into hyperplasia involving the
      entire epithelium and then low-grade dysplasia. Reactive stromal proliferation
      was induced and continued to develop throughout the progression to high-grade
      dysplasia, carcinoma in situ, and adenocarcinoma. Immunohistochemical studies
      indicated that most stromal cells stained positively for both androgen receptor
      and smooth muscle alpha-actin, suggesting that stromal overgrowth largely
      represented mesenchymal cells that had differentiated into smooth muscle cells.
      Epithelial cell transformation was accompanied by the down-regulation of
      differentiated function, as suggested by the loss of dorsolateral prostate
      specific secretory proteins. Tumor growth was regarded as androgen-dependent
      because tumors regressed in animals castrated at 11 weeks of age, and androgen
      treatment restored both epithelial/stromal cell ratio and tumor growth.
      Furthermore, small populations of prostatic epithelial cells in castrated animals
      continued to proliferate, suggesting the potential for androgen-independent
      growth. Although prostatic metastasis to other organs was not observed, local
      invasion was detected. In summary, the LPB-Tag animal model is unique in that it
      is the only model generated with the Tag alone, thereby eliminating any
      influences of the small t antigen on prostate tumor formation. Moreover, this
      model undergoes molecular changes similar to those found in human prostate
      including: (a) the multi-focal nature of tumorigenesis, (b) the progressive
      histopathologic changes from low- to high-grade dysplasia similar to human
      prostatic intraepithelial neoplasia, (c) stimulation of reactive stromal
      proliferation, and (d) the androgen-dependent growth of the primary tumor. Thus,
      the LPB-Tag prostate tumor model will be useful for studying the sequential
      mechanisms underlying the development of multistep tumorigenesis.

PMID- 9645769
TI  - Superior survival of young women with malignant melanoma.
AB  - BACKGROUND: The Commission on Cancer data from the National Cancer Data Base
      (NCDB) relating to patients with malignant melanoma are used to examine patterns
      of long-term survival by patient gender and age, stage of disease, disease
      morphology, and anatomic subsite. METHODS: Five calls for data have yielded more
      than 3,700,000 cases of cancer for the years 1985 through 1993, including 23,341
      cases of malignant melanoma between 1985 and 1989, from hospital cancer
      registries across the US, representing slightly less than a quarter of all
      melanoma cases diagnosed in the US between 1985 and 1989. RESULTS: Three
      statements can be made from this data: (1) There is little difference in the
      frequency of malignant melanoma between men and women with respect to stage of
      disease or morphology. However, differences between the genders do appear with
      respect to the anatomic subsite of melanotic tumors. (2) Overall, young women (45
      years of age and under) enjoy superior survival rates when compared with older
      women (55 years of age and older) and men of any age. (3) The survival advantage
      held by young women is particularly pronounced among patients diagnosed with
      advanced stage disease. CONCLUSIONS: These data suggest that factors present in
      younger women may be critical in the superior survival rates seen among
      premenopausal women and might be hormonal in nature.

PMID- 9645770
TI  - A single institution's experience with transperitoneal laparoscopic hernia
      repair.
AB  - BACKGROUND: Previous evaluations of endoscopic hernia surgery mostly are based on
      small prospectively documented series or on a few randomized comparative studies.
      In the following, results of a large single-institution experience concerning the
      transabdominal preperitoneal patch (TAPP) technique with regard to the
      development of methods and the routine use are described. METHODS: From April
      1993 to March 1997, 2,700 TAPP procedures were performed at the Department of
      General and Visceral Surgery, Marien-hospital, Stuttgart, Germany. The follow-up
      was documented prospectively in all cases by use of computed data base. RESULTS:
      The majority of patients (83.8%) were operated because of primary hernias. In
      17.2% a first or multiple recurrence of an inguinal hernia was indicated. At a
      median postoperative observation period of presently 20 months and a follow-up
      rate of 86.5%, 28 recurrences have been determined so far (total recurrence rate
      1.03%), 6 of which occurred after a recurrent hernia reparation (1.33%) and 22
      after primary hernia repair (0.97%). The most common cause for recurrence was in
      39.3% a mesh (12 x 8 cm) being too small. The total complication rate was 4.6%;
      as an expression of the learning curve it was reduced from 7.8% (operations 1 to
      500) to 2.8% (operations 2,200 to 2,700). CONCLUSIONS: According to our
      experience, the TAPP technique is sufficiently applicable as a standard method
      for an unselected group of patients in a routine setting. It is especially suited
      to the repair of recurrent and bilateral hernias as well as for patients with a
      high risk for recurrence that can profit from a tension-free endoscopic
      procedure, particularly in case of obesity.

PMID- 9645771
TI  - Intrahepatic biliary enteric bypass provides effective palliation in selected
      patients with malignant obstruction at the hepatic duct confluence.
AB  - BACKGROUND: Palliating the effects of biliary obstruction is a major goal of
      therapy in patients with cancer at the hepatic duct confluence. This study was
      undertaken to evaluate the effectiveness of intrahepatic biliary-enteric bypass
      to either the segment III duct or the right sectoral hepatic ducts in patients
      with unresectable hilar cholangiocarcinoma or gallbladder carcinoma. METHODS:
      From December 1991 to October 1996, 55 consecutive bypass procedures were
      prospectively evaluated in patients with unresectable hilar cholangiocarcinoma or
      gallbladder cancer. Patients were divided into three groups based on the primary
      tumor and the type of bypass performed: group 1A, cholangiocarcinoma/segment III
      bypass (n = 20); group 1B, cholangiocarcinoma/right sectoral hepatic duct bypass
      (n = 14); group 2, gallbladder cancer/segment III bypass (n = 21). RESULTS: Mean
      hospital stay (14+/-2 days) and mean blood loss (629+/-84 mL) were similar among
      the three groups. Perioperative death occurred in 6 patients (11%): 0 in group
      1A, 3 each in groups 1B and 2. All survivors had relief of jaundice and pruritus
      after bypass. Complications occurred in 25 patients (45%). Preoperative
      transhepatic biliary drainage, performed in 14 patients prior to referral, was
      associated with a higher incidence of contaminated bile, greater operative blood
      loss, and postoperative biliary leak that was less likely to resolve
      spontaneously. Median survival in patients with cholangiocarcinoma (groups 1A and
      1B) was 52 weeks and was unaffected by the type of bypass performed. By contrast,
      median survival in patients with gallbladder cancer (group 3) was 20 weeks; all
      but 3 died within 32 weeks of surgery. In patients with cholangiocarcinoma, the 1
      year bypass patency was 80% in group 1A (segment III bypass) and 60% in group 1B
      (right sectoral hepatic duct bypass). Overall, there were 9 late bypass failures
      (18%) requiring reintervention. CONCLUSIONS: Intrahepatic biliary-enteric bypass
      effectively relieves symptoms due to malignant hilar obstruction. In patients
      with cholangiocarcinoma, segment III bypass provides excellent palliation with
      relatively few late complications and can be performed with minimal morbidity and
      mortality. Bypass to the right sectoral hepatic ducts, on the other hand, is
      associated with significant procedure-related morbidity and mortality and more
      late complications. Patients with gallbladder cancer, because of their poor
      survival, are probably better palliated by percutaneous biliary stenting.

PMID- 9645772
TI  - Use of preoperative autologous blood donation in liver resections for colorectal
      metastases.
AB  - BACKGROUND: Transfusion of allogeneic blood is associated with risks of human
      immunodeficiency virus and hepatitis transmission, transfusion reactions, and
      other potential immunologic and infectious complications. To determine if
      predonation of autologous blood impacts upon transfusion practice and clinical
      outcome following liver resection, clinical records of 379 consecutive patients
      undergoing hepatic resection for metastases of colorectal cancer were identified
      from the prospective hepatobiliary database and reviewed. METHODS: Of the 379
      hepatic resections performed for colorectal metastases between January 1991 and
      January 1996, 240 (63%) were hepatic lobectomy or trisegmentectomy. Thirty-two
      percent of patients (123 of 379) agreed to preoperative blood donation (POBD),
      and their clinical characteristics including age, preoperative hemoglobin, and
      operative mortality were comparable with those of patients without POBD. Liver
      resections were carried out using standard vascular inflow and outflow control.
      Parenchymal transections were performed bluntly with maintenance of low central
      venous pressure (0 to 5 cm H2O). No vascular isolation or normovolemic
      hemodilution was used intraoperatively. All erythrocyte transfusions during the
      entire hospital stay were considered and compared between the two groups.
      RESULTS: Forty-five percent of patients (172 of 379) received blood transfusions
      during or after liver resections, of which 61% (105 of 172) required only 1 or 2
      units. Only 17% of the POBD group required allogeneic blood. This was
      significantly less than the group without POBD (43%, P <0.01). There was no
      significant difference in the operative mortality (2.3% versus 4.9%, P = 0.2) and
      the median survival (50 versus 40 months, P = 0.3). CONCLUSIONS: Major hepatic
      resections using current surgical techniques can be performed safely with low
      blood loss and transfusion is required for only a minority of patients. POBD
      further reduces transfusion requirement.

PMID- 9645773
TI  - Management of true aneurysms of the splenic artery.
AB  - BACKGROUND: Splenic artery aneurysms (SAA) are detected with increasing frequency
      but their management still remains controversial. This paper relates our
      experience in the outcome and management of ruptured aneurysms of the splenic
      artery. METHODS: Between 1977 and 1996, 8 patients presented to our institution
      with a ruptured SAA. Their ages ranged from 25 to 72 years (mean 55 ys). RESULTS:
      All patients presented with rupture as the first sign of SAA. One patient was at
      32 weeks of gestation and rupture suggested placental abruption. Three patients
      required cardiopulmonary reanimation prior to surgical procedures.
      Splenopancreatectomy (n = 4), splenectomy (n = 2), and ligation of the splenic
      artery (n = 1) were performed. Seven of the 8 patients survived. Size of
      aneurysms ranged from 2 cm to 3.5 cm (mean 3 cm). CONCLUSIONS: SAA may rupture at
      any age. Diagnosis during pregnancy rests upon a high index of suspicion. The
      mortality rate remains low if immediate resuscitation is performed and an
      aggressive surgical approach is taken.

PMID- 9645775
TI  - Interpretation of postvagotomy endoscopic Congo red test results in relation to
      ulcer recurrence 5 to 12 years after operation.
AB  - BACKGROUND: The aim of the present study was to estimate, after vagotomy, the
      location and extension of residual vagal innervation of the gastric corpus mucosa
      by using the endoscopic Congo red test (ECRT) and its relation to recurrent ulcer
      (RU), as well as the results of quantitative gastric acid tests: basal acid
      output (BAO), maximal acid output (MAO), and nocturnal acid output (NAO).
      METHODS: A total of 271 consecutive vagotomized duodenal ulcer (DU) patients were
      studied 5 to 12 years (mean 8 years) after the operation. In all cases
      gastroscopy and ECRT were performed simultaneously. ECRT was considered positive
      if a red to black-blue (pH <3.0) color change of the gastric corpus mucosa
      occurred within the first 3 minutes, and the cases were classified as having
      small extension (SE), ie, one or more areas with a diameter of 1 to 30 mm, or
      large extension (LE), ie, 20% or more of the gastric corpus showing residual
      vagal innervation. No red to black-blue changes (pH >3.0) were attributed to
      negative ECRT. BAO, MAO, and NAO were determined preoperatively and
      postoperatively in 108 cases out of 271 and correspond with ECRT results.
      RESULTS: Recurrent ulcer occurred in 18 out of 135 ECRT-positive and in 1 out of
      136 ECRT-negative cases. RU occurred 5 times more frequently in LE than SE cases
      (P <0.05). The postoperative mean values of BAO, MAO, and NAO were significantly
      higher in ECRT-positive than in ECRT-negative cases (P <0.001), and higher in LE
      than in SE cases (P <0.01; for NAO, P >0.05). CONCLUSION: ECRT is a practical and
      reliable method in the evaluation of postvagotomy DU patients: Negative ECRT
      practically includes recurrent ulcer risk; positive ECRT of large extension is
      related to fivefold higher recurrent ulcer risk compared with ECRT of small
      extension; and ECRT reflects BAO, MAO, and NAO results and can be used instead of
      them as a less time-consuming procedure, which is more convenient for the
      patient.

PMID- 9645774
TI  - Transfusion of phosphoenolpyruvate-treated blood increases oxygen consumption in
      acute hemorrhage.
AB  - BACKGROUND: Incubating blood with phosphoenolpyruvate decreases hemoglobin oxygen
      affinity (HOA). This study compared transfusion with phosphoenolpyruvate-treated
      blood and conventionally stored blood on oxygen consumption in acutely anemic
      dogs. METHODS: Dogs underwent isovolemic hemodilution (hematocrit = 10%). After 1
      hour they were transfused to a hematocrit of 18% with control or
      phosphoenolpyruvate treated blood. Cardiac output, co-oxymetry, and hemoglobin
      P50 measurements allowed calculation of oxygen consumption during anemia, and
      posttransfusion. RESULTS: Hemodilution doubled cardiac output. Transfusion with
      phosphoenolpyruvate-treated blood allowed greater O2 consumption than control
      (8.31+/-2.1 and 3.73+/-0.11 cc/kg/mm). There were no differences in arterial or
      venous PO2 or pH; there were marked differences in HOA, measured by
      posttransfusion P50 (21+/-3 versus 47+/-4), and mixed venous O2 saturation.
      CONCLUSIONS: Decreased HOA results in increased O2 consumption in dogs subjected
      to anemic hypoxia. Phosphoenolpyruvate-treated blood provides increased oxygen
      consumption at a similar hematocrit when compared with untreated banked blood.

PMID- 9645776
TI  - Intraoperative cytodiagnosis for detecting a minute invasion of the portal vein
      during pancreatoduodenectomy for adenocarcinoma of the pancreatic head.
AB  - During pancreatoduodenectomy for adenocarcinoma of the pancreatic head, we
      frequently encountered cases in which the superior mesenteric-portal venous
      confluence (SMPVC) was involved with cancer. With regard to the indication of the
      concomitant SMPVC resection, as suggested by recent papers, a better long-term
      outcome would be expected if the cancer invasions were limited to the tunica
      adventitia or media of the SMPVC wall. Since this raised fears whether such a
      small SMPVC invasion was always detectable by macroscopic inspection alone, we
      have performed an intraoperative cytology on the touch smear of the exposed SMPVC
      wall for 23 patients with pancreatic head cancer. All of their SMPVCs were
      separated from the pancreatic head and appeared to be intact at a macroscopic
      level. As a result of the cytologic examination, however, 7 patients (30%) were
      newly diagnosed as having cancer cells on the SMPVC wall, and they received an
      additional resection of the SMPVC. Postoperative histology indicated that cancer
      invasion into the SMPVC wall was present in 6 of the 7 patients, and that the
      cancer invasions were limited in the tunica adventitia in 5 patients and to the
      tunica media in 1 patient. Thus, in order not to miss the chance of cure by SMPVC
      resection, our intraoperative cytology on the touch smear of the SMPVC is worth
      performing more actively on the macroscopically intact-looking SMPVC during
      resection of pancreatic cancer.

PMID- 9645777
TI  - Development of a model for training and evaluation of laparoscopic skills.
AB  - BACKGROUND: Interest in the training and evaluation of laparoscopic skills is
      extending beyond the realm of the operating room to the use of laparoscopic
      simulators. The purpose of this study was to develop a series of structured tasks
      to objectively measure laparoscopic skills. This model was then used to test for
      the effects of level of training and practice on performance. METHODS: Forty-two
      subjects (6 each of surgical residents PGY1 to PGY5, 6 surgeons who practice
      laparoscopy and 6 who do not) were evaluated. Each subject viewed a 20-minute
      introductory video, then was tested performing 7 laparoscopic tasks (peg
      transfers, pattern cutting, clip and divide, endolooping, mesh placement and
      fixation, suturing with intracorporeal or extracorporeal knots). Performance was
      measured using a scoring system rewarding precision and speed. Each candidate
      repeated all 7 tasks and was rescored. Data were analyzed by linear regression to
      assess the relationship of performance with level of residency training for each
      task, and by ANOVA with repeated measures to test for effects of level of
      training, of repetition, and of the interaction between level of training and
      repetition on overall performance. Student's t test was used to evaluate
      differences between laparoscopic and nonlaparoscopic surgeons and between each of
      these groups and the PGY 5 level of surgical residents. RESULTS: Significant
      predictors of overall performance were (a) level of training (P = 0.002), (b)
      repetition (P < 0.0001), and (c) interaction between level of training and
      practice (P = 0.001). There was also a significant interaction between level of
      training and the specific task on performance scores (P = 0.006). When each task
      was evaluated individually for the 30 residents, 4 of the 7 tasks (tasks 1, 2, 6,
      7) showed significant correlation between PGY level and score. A significant
      difference in performance scores between laparoscopic and nonlaparoscopic
      surgeons was seen for tasks 1, 2, and 6. CONCLUSIONS: A model was developed to
      evaluate laparoscopic skills. Construct validity was demonstrated by measuring
      significant improvement in performance with increasing residency training, and
      with practice. Further validation will require correlation of performance in the
      model with skill in vivo.

PMID- 9645778
TI  - Posterior or laparoscopic approach for adrenalectomy.
AB  - BACKGROUND: The pathologies and size of adrenal lesions removed through the open
      posterior and laparoscopic routes share remarkable similarities. This study aims
      at comparing the relative merits of these two approaches. METHODS: Patients with
      adrenal tumors operated on by posterior approach (n = 56) and transabdominal
      laparoscopic approach (n = 12) between January 1981 and May 1997 were
      retrospectively reviewed. RESULTS: The two groups were comparable in terms of
      age, and the position, size, and weight of the tumor. The operative time of
      posterior adrenalectomy was significantly shorter than that of laparoscopic
      adrenalectomy (median 120 minutes versus 160 minutes), whereas laparoscopic
      adrenalectomy was associated with less parenteral analgesic requirement (median 0
      mg versus 225 mg), a shorter hospital stay (median 3 days versus 5 days), and a
      shorter duration off work (median 11 days versus 26 days). The estimated blood
      loss was also significantly reduced in the laparoscopic group (median 50 mL
      versus 150 mL). CONCLUSIONS: Laparoscopic adrenalectomy is replacing posterior
      adrenalectomy to become the procedure of choice for the majority of patients
      undergoing adrenalectomy.

PMID- 9645779
TI  - Ultrasonically activated shears in thyroid surgery.
AB  - BACKGROUND: Ultrasonically activated shears (UAS) have been documented to be both
      safe and fast devices in laparoscopic surgery. We studied whether the use of UAS
      would have some advantage in thyroid surgery. METHODS: Thyroidectomies, performed
      by one senior endocrine surgeon between December 1996 and February 1997, were
      retrospectively matched, with patients operated on by the same surgeon using the
      conventional method. RESULTS: Six pairs of total thyroidectomies and one pair of
      lobectomies could be matched. Mean operating time was 100 minutes for the
      patients operated on with the UAS and 154 minutes for the patients operated on
      with the conventional method. The mean operating time with the UAS was thus on
      average 64.6% of the operation time with the conventional method, with a 95%
      confidence interval from 50.1% to 83.5% (t = 4.00, 6 df, P = 0.007). CONCLUSIONS:
      In this material the use of UAS reduced significantly operating time in
      thyroidectomies.

PMID- 9645780
TI  - Rapid arterial anastomosis with titanium clips.
AB  - BACKGROUND: The obvious advantages of rapid arterial anastomoses have prompted
      the continuing search for more rapid anastomotic techniques to complement the
      standard sutured anastomosis. Nonpenetrating, arcuate-legged titanium vascular
      closure staple (VCS) clips were initially developed for microvascular
      anastomoses. The purpose of this study was to compare VCS clips with sutured
      arterial end-to-end anastomosis in larger vessels. METHODS: In 6 pigs, transacted
      iliac arteries were reanastomosed with VCS clips on one side and continuous 6-0
      polypropylene suture on the other. RESULTS: The reconstruction time was 8.4+/-5.2
      minutes for clip closure and 12.0+/-6.6 minutes for suture closure (P = 0.033).
      All vessels were patent half an hour after completing the anastomoses with no
      signs of early thrombosis. CONCLUSIONS: Arterial end-to-end anastomosis can be
      performed more rapidly with VCS clips than continuous sutures, and are
      potentially useful in situations where the clamp time of the vessel is critical.

PMID- 9645781
TI  - Do our current assessments assure competency in clinical breast evaluation
      skills?
AB  - BACKGROUND: The focus of teaching for clinical breast evaluation has been the
      technique of breast examination. This study questions the relationship between
      breast examination technique and the ability to detect physical findings.
      METHODS: This study examines the relationship between breast examination skills
      of 66 graduating primary care physicians as measured during an objective
      structured clinical examination (OSCE) and lump detection sensitivity and
      specificity on breast models. RESULTS: Overall breast examination performance
      revealed 50% of maneuvers performed correctly. Mean breast model sensitivity for
      lump detection was 40% and the mean breast model specificity was 77%. While a
      mild correlation existed between breast examination skills and lump detection
      sensitivity (r = .34, P = 0.01), no relationship was found between lump detection
      specificity and examination skills. CONCLUSIONS: There is a limited relationship
      between correct performance of breast examination maneuvers and the ability to
      detect a breast lump when present. Breast examination skills and palpation skills
      to detect masses may represent independently acquired skills with need for
      separate instructional methodology. These results raise serious concerns about
      the reliance on standardized patients alone for training in physical examination
      skills.

PMID- 9645782
TI  - Unstructured cases in case-based learning benefit students with primary care
      career preferences.
AB  - BACKGROUND: The impact of instructional method on students with opposing surgical
      career orientations was investigated in a prospective study. METHODS: Students
      were randomly assigned to structured or unstructured case-based discussions.
      Clinical reasoning (OSCE and a diagnosis exercise), subject knowledge (multiple
      choice test [MCT]), method preference, and pre-third year career preference were
      compared. RESULTS: Twenty-two students listed a surgical career high (Surgical)
      and 20 low (Primary). Surgical MCT scores were higher than Primary regardless of
      instructional method. Surgical diagnosis exercise scores were higher than Primary
      with the structured method (22.0+/-2.3 versus 15.1+/-3.0, P <0.08). Unstructured
      scores on this exercise were similar (19.7+/-1.8 Surgical versus 20.3+/-3.5
      Primary). Analysis of variance suggested an interaction on the diagnosis exercise
      between method and career (P = 0.16). Students preferred the unstructured method.
      CONCLUSIONS: The improved diagnosis exercise performance implies that
      unstructured cases positively influence surgical domain specific reasoning for
      nonsurgical career students. These method effects increase our understanding of
      case-based methods in surgical education.

PMID- 9645783
TI  - Computer-assisted learning versus a lecture and feedback seminar for teaching a
      basic surgical technical skill.
AB  - BACKGROUND: Rapid improvements in computer technology allow us to consider the
      use of computer-assisted learning (CAL) for teaching technical skills in surgical
      training. The objective of this study was to compare in a prospective, randomized
      fashion, CAL with a lecture and feedback seminar (LFS) for the purpose of
      teaching a basic surgical skill. METHODS: Freshman medical students were randomly
      assigned to spend 1 hour in either a CAL or LFS session. Both sessions were
      designed to teach them to tie a two-handed square knot. Students in both groups
      were given knot tying boards and those in the CAL group were asked to interact
      with the CAL program. Students in the LFS group were given a slide presentation
      and were given individualized feedback as they practiced this skill. At the end
      of the session the students were videotaped tying two complete knots. The tapes
      were independently analyzed, in a blinded fashion, by three surgeons. The total
      time for the task was recorded, the knots were evaluated for squareness, and each
      subject was scored for the quality of performance. RESULTS: Data from 82 subjects
      were available for the final analysis. Comparison of the two groups demonstrated
      no significant difference between the proportion of subjects who were able to tie
      a square knot. There was no difference between the average time required to
      perform the task. The CAL group had significantly lower quality of performance (t
      = 5.37, P <0.0001). CONCLUSIONS: CAL and LFS were equally effective in conveying
      the cognitive information associated with this skill. However, the significantly
      lower performance score demonstrates that the students in the CAL group did not
      attain a proficiency in this skill equal to the students in the LFS group.
      Comments by the students suggest that the lack of feedback in this model of CAL
      was the significant difference between these two educational methods.

PMID- 9645784
TI  - Does volume of patients seen in an outpatient setting impact test scores?
AB  - BACKGROUND: Methods of teaching surgery in the outpatient setting and means to
      measure the effectiveness of these methods have not been defined. This study was
      designed to evaluate the impact of number of outpatient encounters on test scores
      for third-year medical students. METHODS: Students rotating on the required third
      year surgery clerkship between July 1994 and June 1996 kept a log of their
      activities including number of patients seen in clinic, number of cases scrubbed,
      and pages read. At the end of the rotation the students were given an essay
      examination and a multiple-choice examination. The data were analyzed looking for
      correlation between examination scores and volume of patients seen. United States
      Medical Licensing Examination (USMLE) Step 1 scores were used as a baseline
      measure to compare the rotation groups. RESULTS: USMLE scores did not differ
      between groups. Mean essay examination scores varied significantly between some
      rotation groups, but did not follow a pattern. There was no correlation between
      the number of patients seen in clinic and essay examination scores. There was a
      significant correlation between essay score and USMLE Step 1 score (Pearson's r =
      0.398) and between essay and multiple-choice examination scores (Pearson's r =
      0.313). There was a significant negative correlation between number of patients
      seen in clinic and number of cases scrubbed (Pearson's r = -0.347). CONCLUSIONS:
      Participation in outpatient surgery clinics did not result in improved
      performance on written examinations in this surgery clerkship. To achieve the
      most benefit from the outpatient clinic, objectives of the experience need to be
      determined and appropriate tools used to measure their successful achievement.

PMID- 9645785
TI  - Is a mandatory general surgery rotation necessary in the surgical clerkship?
AB  - BACKGROUND: Changes in the spectrum of general surgery and the delivery of
      surgical care have placed the requirement for a mandatory general surgery
      rotation in the surgical clerkship in question. METHODS: We tested the hypothesis
      that equal mastery of surgical clerkship objectives can be obtained in a
      clerkship with and without general surgery. Students chose any two surgical
      rotations and were assessed by written examination, objective structured clinical
      examination (OSCE), ward evaluations, self-assessment objectives questionnaire,
      and satisfaction survey. RESULTS: Data for 54 students showed no differences in
      scores between groups on any parameter. No specific concerns related to the
      absence of general surgery were identified. CONCLUSIONS: Effective undergraduate
      surgical education can be offered in many specialty settings. Removal of the
      requirement for general surgery in clerkship may lead to a more effective use of
      all educational opportunities. A careful analysis of local programs and
      facilities is necessary before suggesting this change to other institutions.

PMID- 9645786
TI  - Can a one-day workshop alter surgeons' teaching practices?
AB  - BACKGROUND: A 1-day workshop, consisting of five sections with small group
      discussions and opportunities for practical application of participants'
      knowledge, was developed to enhance the teaching skills of practicing surgeons.
      Immediate and long-term follow-up surveys were completed by the participants.
      METHODS: Post-workshop evaluations were obtained from all participants who took
      the workshop; follow-up surveys were mailed 4 to 6 months later. RESULTS:
      Workshop quality was rated as good (25%) or excellent (75%) by all participants.
      Follow-up survey results indicated that many participants had rarely/never
      utilized cited references, looked for additional resources on specific topics, or
      referred to the section syllabus/handout materials provided during the workshop.
      However, 100% of the participant respondents reported that they had changed the
      way they teach as a result of their workshop attendance. CONCLUSION: An
      abbreviated course on surgical education can result in long-term changes in the
      participants' perceptions of their teaching practices. Further study is required
      to determine if these perceived changes in teaching practices, which the
      participants have directly attributed to their workshop attendance, have resulted
      in measurable improvement in their effectiveness and efficiency as teachers.

PMID- 9645787
TI  - Analysis of case-control studies of the efficacy of screening for cancer: How
      should we deal with tests done in persons with symptoms?

PMID- 9645788
TI  - Maternal smoking, body mass index, and neural tube defects.
AB  - The Swedish health registries were used to investigate a possible effect on the
      incidence of neural tube defects (NTDs) of maternal smoking and maternal body
      mass index (BMI) (kg/m2). Among 1,199,701 infants born in 1983-1993 with known
      smoking exposure in early pregnancy, 621 infants with NTDs were selected. After
      controlling for year of birth, maternal age, parity, education level, BMI, and
      immigrant status (yes/no), a highly significant, protective effect of maternal
      smoking on the incidence of NTDs was found. The adjusted odds ratios (OR) and
      (95% confidence intervals (CI)) for maternal smoking among infants with NTDs
      (total), anencephaly, and spina bifida were 0.75 (0.61-0.91), 0.49 (0.28-0.85),
      and 0.76 (0.61-0.95), respectively. A protective dose-response effect of smoking
      was indicated but was not statistically significant. The association between NTDs
      and maternal BMI found in earlier studies was supported. Women with BMI >26.0
      were found to be at higher risk of having an infant with NTD compared with women
      in other BMI classes (adjusted OR=1.35, 95% CI 1.00-1.83). For women with BMI >
      or =29, the corresponding odds ratio was 1.29 (0.81-2.05). No obvious explanation
      was found, either for the detected association between NTDs and BMI, or for the
      protective effect of maternal smoking.

PMID- 9645789
TI  - Epidemiologic interpretation of artificial neural networks.
AB  - Multilayer neural networks have been faulted for functioning as "black boxes" and
      for failing to assess the relative importance of the input factors. The aim of
      this paper is to illustrate how neural networks can classify individuals. The
      authors investigated the role of weights in the formation of neural networks'
      decision surfaces and decision regions. The data used were from a case-control
      study. Two strong determinants of case status were used as input "neurons." Zero,
      three, and five hidden neurons were used to explore the effect of the number of
      hidden neurons on the decision surfaces and regions. Mapping of input and output
      spaces revealed that three hidden neurons were insufficient to fully discriminate
      cases from controls. Five hidden neurons may be optimal, but at the cost of
      possible over-fitting. The more complex neural networks were very effective at
      defining regions of uniform risk in the plane of the initial covariates, and at
      assigning risk levels. The authors speculate that neural networks will prove
      useful in epidemiologic problems that require pattern recognition or complicated
      classification techniques, and that they will be unfavorable in problems that
      involve distinct effects of distinguishable predictors.

PMID- 9645790
TI  - Correction for biases in a population-based study of family history and coronary
      heart disease. The Newcastle Family History Study I.
AB  - In this paper, the authors report on the design of a population-based case
      control study of family history as a risk factor for coronary heart disease
      (CHD). They studied the characteristics of subjects who completed a detailed
      family history questionnaire in 1992-1994 as well as the accuracy of recall of
      family history in order to quantify both selection and recall biases. Coronary
      disease cases were enrolled through the Newcastle MONICA Project (Monitoring
      Trends and Determinants in Cardiovascular Disease), which registered all
      suspected heart attacks and sudden cardiac deaths in the Lower Hunter region of
      New South Wales, Australia, between August 1984 and March 1994. Controls were
      selected at random from the New South Wales electoral roll. The response rate was
      76% in cases and 62% in controls; the major factor associated with participation
      in the study was perceived family history of CHD, more so in the control series
      than in the case series. Accuracy was determined by comparing information
      obtained from the proband with that recorded on death certificates. In first
      degree relatives, sensitivity of CHD recall was 85% (95% confidence interval (CI)
      74-92%) in cases and 95% (95% CI 84-99%) in controls, while specificity was 59%
      (95% CI 49-69%) and 74% (95% CI 65-82%), respectively. The net bias in both
      selection and recall is toward the null and hence the comparisons provide a
      conservative estimate of risk of CHD associated with a positive family history.

PMID- 9645791
TI  - Risk associated with various definitions of family history of coronary heart
      disease. The Newcastle Family History Study II.
AB  - The authors carried out a population-based case-control study to estimate the
      risk of an acute coronary disease event associated with various definitions of a
      family history of coronary heart disease (CHD). A detailed family history
      questionnaire was completed by 403 cases and 236 controls in Newcastle, New South
      Wales, Australia from 1992 to 1994. Odds ratios of an acute coronary disease
      event adjusted for proband age and sex ranged from 2.7 (95% confidence interval
      (CI) 1.8-4.1) for the simplest definition (one or more first-degree relatives
      with CHD at any age) to 5.4 (95% CI 1.7-16.8) for the most stringent definition
      (two or more first-degree relatives with CHD before age 55 years). In a series of
      nested models, the authors examined the improvement in model fit as each
      component of the detailed family history was added. Additional information was
      provided by accounting for "don't know" responses, the number of affected
      relatives, the age of the affected relative, and whether the first-degree
      relative was a sibling rather than a parent. The results were similar when the
      data were analyzed as a cohort design with proband disease status as the exposure
      variable. The authors suggest that, to facilitate preventive efforts in a
      population, more detailed family history definitions should be used to better
      target high risk subjects.

PMID- 9645792
TI  - Retrospective analysis of birth weight and prostate cancer in the Health
      Professionals Follow-up Study.
AB  - The authors retrospectively evaluated the relation between birth weight and
      prostate cancer (1986-1994) among 21,140 men of the Health Professionals Follow
      up Study who reported in 1994 their weight at birth. No relation between birth
      weight and prostate cancer (n=545) was observed in multivariate logistic models.
      For high stage/grade tumors (n=213), compared with birth weights <7.0 lbs (<3,175
      g), the relative risks were 1.20 (95% confidence interval (CI) 0.79-1.83) for 8.5
      9.9 lbs (3,855.6-4,490.6 g) and 1.30 (95% CI 0.80-2.10) for > or = 10 lbs (> or =
      4,536 g). These findings do not support an overall association between birth
      weight and prostate cancer incidence, but the possibility of a modest positive
      association between birth weight and high stage/grade prostatic cancer cannot be
      excluded.

PMID- 9645793
TI  - Gender differences in total and allergen-specific immunoglobulin E (IgE)
      concentrations in a population-based cohort from birth to age four years.
AB  - While serum immunoglobulin E (IgE) concentration has been shown to be related to
      allergic disease, there have been few studies of the natural history of IgE
      development in young children. This study compared total and allergen-specific
      serum IgE concentrations, by gender, from birth through 4 years of age using a
      population-based cohort of normal children followed from 1987 to 1993. Subjects
      were enrolled from a geographically defined area through membership in a large
      health maintenance organization, and they resided in the northern suburbs of
      Detroit, Michigan. Total IgE concentrations were measured at birth and at 2 and 4
      years of age. Specific IgE concentrations to selected common inhalant allergens
      (dust mite (Dematophagoides farinae), cat, ragweed (Ambrosia artemisiifolia), and
      timothy grass (Pheleum pratense)) were measured at 2 and 4 years of age. Total
      IgE increased with age from birth to 4 years for boys and girls, and was higher
      in boys at 2 and 4 years of age. Girls demonstrated significant increases in IgE
      to mite and cat and decreases in IgE to ragweed and timothy from 2 to 4 years of
      age, whereas there was little change for boys except an increase in IgE to
      ragweed. Differences in IgE development between young boys and girls may
      partially account for the higher prevalence of asthma in boys than in girls.

PMID- 9645794
TI  - Reliability of self-reported sexual behavior in human immunodeficiency virus
      (HIV) concordant and discordant heterosexual couples in northern Thailand.
AB  - A partner study was conducted in northern Thailand between March 1992 and June
      1996 which included data that allowed an assessment of the reliability of self
      reports of sexual behavior and contraceptive use among heterosexual couples. The
      authors enrolled 529 couples among whom all male subjects were human
      immunodeficiency virus (HIV) seropositive voluntary blood donors and their female
      sexual partners were either HIV infected (n=246) or HIV seronegative (n=283). The
      levels of agreement within couples were assessed for recency of last sexual
      intercourse, sexual activity in the prior year, and contraceptive practices. For
      HIV discordant couples, a prospective study was conducted to examine risk factors
      for HIV transmission, the primary goal of the study. This allowed assessment of
      reliability of inter-partner reports over 6-12 months. Overall, agreement among
      couples was good for common sexual practices, especially vaginal intercourse and
      time since last intercourse, but was lower for condom use. Anal and oral sex were
      infrequently reported by these couples and there was greater disagreement for the
      occurrence of these practices. Partner agreement for contraceptive histories was
      good to excellent. Prospective data showed less frequent intercourse and more
      condom use but reliability remained good. Common sexual practices may be reliable
      for both HIV concordant and discordant couples in studies estimating prevalent
      infection. Estimates of incident heterosexually transmitted HIV may be made with
      greater reliability by studies which include assessment of reports of risk
      behavior by each member of a couple than studies of individuals.

PMID- 9645795
TI  - Relation of nutrition to bone lead and blood lead levels in middle-aged to
      elderly men. The Normative Aging Study.
AB  - The relations of nutritional factors to lead accumulation in the body were
      examined cross-sectionally among 747 men aged 49-93 years (mean 67 years) in the
      Normative Aging Study in 1991-1995. Means (standard deviations) for blood lead,
      tibia lead, and patella lead were 6.2 (4.1) microg/dl, 21.9 (13.3) microg/g, and
      32.0 (19.5) microg/g, respectively. In multiple regression models adjusting for
      age, education level, smoking, and alcohol consumption, men in the lowest
      quintile of total dietary intake levels of vitamin D (including vitamin
      supplements) (<179 i.u./day) had mean tibia and patella lead levels 5.6 microg/g
      and 6.0 microg/g higher than men with intake in the highest quintile (> or =589
      i.u./day). Higher calcium intake was associated with lower bone lead levels, but
      this relation became insignificant when adjustment was made for vitamin D. The
      authors also observed inverse associations of blood lead levels with total
      dietary intake of vitamin C and iron. When analyses were controlled for patella
      lead, age, smoking, and alcohol consumption, men in the lowest vitamin C intake
      quintile (<109 mg/day) had a mean blood lead level 1.7 microg/dl higher than men
      in the highest quintile (> or =339 mg/day), while men in the lowest iron intake
      quintile (<10.9 mg/day) had a mean blood lead level 1.1 microg/dl higher than men
      in the highest quintile (> or =23.5 mg/day). This study suggests that low dietary
      intake of vitamin D may increase lead accumulation in bones, while lower dietary
      intake of vitamin C and iron may increase lead levels in the blood.

PMID- 9645797
TI  - Prevention of primary islet isograft nonfunction in mice with pravastatin.
AB  - BACKGROUND: Nonspecific inflammatory damage in the early stages of
      transplantation is the major cause of primary islet graft nonfunction. Using
      murine isografts, we attempted to prevent this islet graft damage by treating
      recipients with pravastatin (Pravacol), a 3-hydroxy-3-methylglutaryl-coenzyme A
      reductase inhibitor. Nicotinamide was also tested to determine the synergistic
      effect of both agents. METHODS: Unpurified newborn BALB/c islets, ranging in
      number from 1800 to 2500, were transplanted into the left renal subcapsular space
      of a syngeneic adult mouse made diabetic with streptozotocin. Recipient mice were
      divided into the following four groups, based on treatment protocols: treatment
      with 40 mg/kg pravastatin (group 1), 500 mg/kg nicotinamide (group 2), 40 mg/kg
      pravastatin and 500 mg/kg nicotinamide (group 3), and vehicle alone (group 4).
      Pravastatin and nicotinamide were administered orally every day for 14 days,
      starting on the day of transplantation (day 0). Nonfasting blood glucose levels,
      urine glucose levels, and the intravenous glucose tolerance test were used to
      monitor the diabetic state. The reversal of diabetes was defined by normoglycemia
      and negative urine glucose maintained for more than 7 days. RESULTS: After islet
      transplantation, levels of blood and urine glucose were significantly lower in
      groups 1 and 3, compared with those in group 4. K-values of an intravenous
      glucose tolerance test performed on day 14 were significantly higher in groups 1
      and 3 than those of group 4. Reversal of diabetes had occurred in 63% of mice in
      group 1 and 67% in group 3, levels that were higher than those in group 2 (17%)
      and group 4 (0%) (P<0.02, groups 1 and 3 vs. group 4). Histological examination
      of grafts, biopsied on day 21, revealed well preserved islets with little sign of
      inflammation in groups 1 and 3, whereas grafts in groups 2 and 4 contained
      broken, smaller islets surrounded by severe fibrosis and mononuclear cell
      infiltration. CONCLUSION: Our results in mice have shown the effectiveness of
      pravastatin for protecting islets from nonspecific inflammatory damage.
      Nicotinamide did not show a synergistic effect with pravastatin at the dosage
      used in this study. These results indicate that pravastatin may be a useful agent
      for clinical islet transplantation.

PMID- 9645796
TI  - Prolonged acceptance of concordant and discordant xenografts with combined CD40
      and CD28 pathway blockade.
AB  - BACKGROUND: The prompt and vigorous immune response to xenogenic tissue remains a
      significant barrier to clinical xenotransplantation. Simultaneous blockade of the
      CD28 and CD40 costimulatory pathways has been shown to dramatically inhibit the
      immune response to alloantigen. METHODS: . In this study, we investigated the
      ability of simultaneous blockade of the CD28 and CD40 pathways to inhibit the
      immune response to xenoantigen in the rat-to-mouse and pig-to-mouse models.
      RESULTS: Simultaneous blockade of the CD28 and CD40 pathways produced marked
      inhibition of the cellular response to xenoantigen in vivo and produced long-term
      acceptance of xenogeneic cardiac and skin grafts (rat-to-mouse), and markedly
      suppressed an evoked antibody response to xenoantigen. In addition, this strategy
      significantly prolonged the survival of pig skin on recipient mice. CONCLUSIONS:
      Long-term hyporesponsiveness to xenoantigen across both a concordant and
      discordant species barrier, measured by the stringent criterion of skin grafting,
      can be achieved using a noncytoablative treatment regimen.

PMID- 9645798
TI  - A new and simple technique of total hepatic ischemia in the mouse.
AB  - BACKGROUND: A model of total hepatic ischemia is currently not available in mice.
      Models described in rats using portosystemic shunts to achieve total ischemia
      have been notoriously difficult. In mice, the problem is compounded further when
      using this type of technique because of the small size of the animal. A new
      technique is described combining partial hepatectomy with clamping of the remnant
      liver. METHODS: A partial (30%) hepatectomy is performed with resection of the
      caudate, right lateral, and quadrate lobes, and papillary process. Vascular
      microclamps are placed across the pedicles of the median and left lateral lobe at
      the level of the hilum to achieve total ischemia. Spontaneous portocaval shunts
      through caudate branches and collateral vessels prevent mesenteric congestion.
      Animals were studied for survival. RESULTS: The procedure consistently took less
      than 30 min (25+/-2 min), and no bleeding of the resected tissue was observed.
      Evidence for total hepatic ischemia and spontaneous shunts was demonstrated by
      the use of an intraportal dye. All animals survived 60 min of ischemia, whereas
      all died after 90 min of ischemia. CONCLUSION: This is a technically simple and
      rapid procedure to perform. In the current environment of multiple knockout mice
      and bioreagents that are available, a model of this type is essential.

PMID- 9645799
TI  - Mouse parvovirus infection potentiates allogeneic skin graft rejection and
      induces syngeneic graft rejection.
AB  - BACKGROUND: The recently identified autonomous mouse parvovirus designated mouse
      parvovirus-1 (MPV-1) persists in adult BALB/c mice for at least 9 weeks, infects
      lymphoid tissues, interferes with the ability of cloned T cells to proliferate,
      and exhibits immunomodulatory properties. As a consequence of these findings, the
      present studies were undertaken to characterize further the inmunomodulatory
      effects of MPV-1 on T cell-mediated immune responses in vivo and in vitro.
      METHODS: To evaluate the effect of MPV-1 infection on CD8+ T cell-mediated
      responses, BALB/c-H2dm2 mice were infected after transplantation of allogeneic
      BALB/c skin. RESULTS: MPV-1 potentiated the rejection of allogeneic skin grafts.
      This potentiation was not a result of virus infecting the cellular or vascular
      component of the graft as determined by in situ hybridization, but was mediated
      by T cells. However, the proliferative capacity of alloantigen-reactive
      lymphocytes from graft-sensitized infected mice was diminished. MPV-1 also
      induced the rejection of syngeneic skin grafts, and T cells from these infected
      graft-sensitized mice lysed syngeneic P815 target cells. CONCLUSIONS: These
      results suggest that MPV-1 infection of skin-grafted mice may disrupt normal
      mechanisms of peripheral tolerance and provide a unique model to study virus
      induced autoimmunity.

PMID- 9645800
TI  - Inhibitory effect of Multiglycosidorum tripterygii on coronary arteriosclerosis
      after heart transplantation.
AB  - BACKGROUND: Graft coronary arteriosclerosis (GCA) is the major limiting factor
      for long-term survival after heart transplantation. In this study, we
      investigated the effect of Multiglycosidorum tripterygii (MT) on GCA and platelet
      derived growth factor A (PDGF-A) mRNA expression of transplanted hearts. METHODS:
      Two groups of Lewis rats (n=7/group) underwent heterotopic heart transplantation
      from Wistar-King donors and were treated with either cyclosporine (CsA;10
      mg/kg/day) or MT (30 mg/kg/ day). Histological evaluations of rejection and
      coronary arteriosclerosis, as well as Northern blot analysis on graft PDGF-A mRNA
      expression were made 60 days after transplantation. RESULTS: Morphometric results
      indicated no significant difference in rejection between the CsA- and MT-treated
      groups. However, the extent of GCA in the MT-treated group was significantly less
      than that seen in the CsA-treated group (P<0.01). The expression of PDGF-A mRNA
      of cardiac allograft was also significantly suppressed in the MT-treated group
      when compared with the CsA-treated group (P<0.01). CONCLUSION: MT is superior to
      CsA in preventing graft coronary arteriosclerosis, and this efficacy is probably
      associated with the depressed expression of graft PDGF-A mRNA in the MT-treated
      group.

PMID- 9645801
TI  - A blinded, long-term, randomized multicenter study of mycophenolate mofetil in
      cadaveric renal transplantation: results at three years. Tricontinental
      Mycophenolate Mofetil Renal Transplantation Study Group.
AB  - BACKGROUND: Three large-scale clinical trials conducted in North America, Europe,
      and Australia showed that mycophenolate mofetil (MMF) decreases the incidence of
      acute renal allograft rejection in the first 6 months after transplant compared
      with placebo or azathioprine. This study extends the randomized, prospective,
      double-blind trial of MMF conducted by the Tricontinental Mycophenolate Mofetil
      Renal Transplantation Study Group. METHODS: Patients (n=503) were randomized to
      receive 100-150 mg of azathioprine (AZA) (n=166), 2 g of MMF (n=173), or 3 g of
      MMF (n=164) per day, in conjunction with cyclosporine and prednisone from the
      time of transplantation. RESULTS: During the first 6 months, the incidence of
      biopsy-proven acute graft rejection (BPR) was reduced by approximately 50% in the
      MMF 2 g (19.7%) and MMF 3 g (15.9%) groups compared with the AZA group (35.5%).
      The incidence of treatment failure during the first 6 months, including BPR,
      death, graft loss, and early withdrawal without prior BPR, was significantly
      decreased: AZA, 50%, compared with MMF 2 g, 38.2% (P=0.0287), and MMF 3 g, 34.8%
      (P=0.0045). At 3 years after transplant, both intent-to-treat and on-study
      (censoring at 90 days after treatment) analyses of graft and patient survival
      showed a trend toward advantage for MMF 2 g and 3 g vs. AZA (intent-to-treat:
      81.9% and 84.8% vs. 80.2%; on-study: 84.0% and 86.4% vs. 82.7%), although this
      trend did not reach statistical significance. Rejection was the principal cause
      of graft loss in all groups: AZA, 9.9%; MMF 2 g, 5.8%; and MMF 3 g, 3.0%. Graft
      function (intent-to-treat and on-study) was comparable in all three groups at 3
      years. Gastrointestinal toxicity, leukopenia, and tissue-invasive cytomegalovirus
      disease were more common in the MMF 3 g group both during and after the first
      posttransplant year. Lymphoproliferative disorders were diagnosed in one AZA
      (0.6%), two MMF 2 g (1.2%), and three MMF 3 g (1.8%) patients. Other (non
      lymphoproliferative disorders, noncutaneous) malignancies occurred in six AZA
      (3.7%), four MMF 2 g (2.3%), and nine MMF 3 g (5.5%) patients. Mortality was
      comparable in all three groups (AZA, 8.6%; MMF 2 g, 4.7%; MMF 3 g, 9.1%) by 3
      years of follow-up. CONCLUSION: MMF significantly reduced the incidence of
      rejection in the first 6 months, but there was not a significant improvement in
      graft survival throughout the 3 years after cadaver kidney transplantation.

PMID- 9645802
TI  - Randomized, double-blind, one-year study of the safety and tolerability of
      cyclosporine microemulsion compared with conventional cyclosporine in renal
      transplant patients. International Sandimmun Neoral Study Group.
AB  - BACKGROUND: A microemulsion formulation of cyclosporine, Neoral, has been
      developed to overcome the problems associated with the poor and variable
      absorption of the traditional oil-based oral formulation, Sandimmune. The present
      study was conducted to compare the safety and tolerability of Neoral versus
      Sandimmune in maintenance renal transplant recipients over 1 year, and to assess
      the number of dose adjustments necessary to maintain trough cyclosporine
      concentrations within the desired therapeutic range. METHODS. Patients on
      Sandimmune were randomized to be converted to Neoral (n=373) or remain on
      Sandimmune (n=93) for 12 months. RESULTS: The proportion of patients needing dose
      increases to maintain cyclosporine trough levels within the desired range was
      significantly higher in the Sandimmune group during the first 3 months of the
      study, whereas the number of patients needing dose reductions was similar in both
      groups throughout the study period. There were no differences between the groups
      in terms of changes in blood pressure, serum creatinine levels, or other
      laboratory parameters. No significant differences in the incidence of adverse
      events known to be related to cyclosporine were observed between the treatment
      groups. More adverse events were causally related to Neoral than to Sandimmune by
      the investigators. However, overall, there were no clinically relevant
      differences between the treatment groups in the main safety and tolerability
      variables. CONCLUSIONS: The results of this study in maintenance renal transplant
      patients suggest that the improved pharmacokinetic characteristics of the
      microemulsion formulation of cyclosporine, Neoral, may facilitate the clinical
      management of cyclosporine immunosuppression, compared with the traditional
      formulation, Sandimmune. Furthermore, there is no evidence that the average
      improved bioavailability of Neoral has a negative impact on the main safety and
      tolerability variables, as no significant differences in graft function, the
      incidence of rejections, and most adverse events were seen.

PMID- 9645803
TI  - Use of aminophylline and enalapril in posttransplant polycythemia.
AB  - BACKGROUND: Posttransplant polycythemia (PTP) affects 6-30% of renal transplant
      recipients and can result in thromboembolic disease. The pathogenesis of PTP
      remains unknown and may be multifactorial. Although phlebotomy has previously
      been the treatment for PTP, drugs such as adenosine receptor antagonists or
      angiotensin-converting enzyme inhibitors can be used to control PTP. METHODS: The
      authors performed a prospective study of two different drugs to treat PTP:
      aminophylline and enalapril. Twenty-seven patients with PTP lasting more than 6
      months were evaluated. During phase 1, aminophylline was compared with enalapril.
      The patients sequentially received aminophylline and enalapril during 12-week
      periods, intercalated by 12-week periods of no drugs. During phase 2, enalapril
      was administered for 12 weeks. RESULTS: From January 1984 to December 1993, 110
      of 333 patients with PTP lasting more than 6 months (33%) developed polycythemia,
      and 27 patients were included in the present study. In phase 1, aminophylline had
      no effect on PTP. Enalapril promoted an erythropoiesis inhibition, characterized
      by a decrease in hematocrit and an increase in iron stores and ferritin levels.
      After withdrawal of enalapril, the hematocrit increased and the iron stores
      decreased. In phase 2, there was a progressive reduction in hematocrit after the
      4th week of therapy. The lowest hematocrit was observed in the 12th week and then
      enalapril was stopped, leading to a subsequent rise in hematocrit. Erythropoietin
      levels and renal function remained constant during all periods of both phases of
      the study. CONCLUSION: The use of adenosine antagonists was ineffective to treat
      PTP in our series. However, treatment with enalapril promoted an erythropoiesis
      inhibition, demonstrated by a reduction in hematocrit, hemoglobin, red blood cell
      count, and reticulocyte count, associated with an increase in iron stores. This
      response occurred independently from erythropoietin levels or hemodynamic graft
      changes.

PMID- 9645804
TI  - A good alternative to reduce the kidney shortage: kidneys from nonheartbeating
      donors.
AB  - BACKGROUND: Because of the shortage of kidneys available for transplantation, we
      began in 1985 to harvest kidneys from non-heartbeating (NHB) donors. METHODS: We
      compared the results of a group of 66 kidney recipients from NHB donors (NHB
      group) with 122 kidney recipients from heartbeating donors (HB group). We
      analyzed, in the NHB group, the influence of ischemia times in graft survival and
      we tested the best cut-offs by receiver operating characteristic curves. We also
      studied, using a univariate and multivariate Cox hazard model, the capacity of
      different variables to predict graft loss. RESULTS: Patient and graft survival
      were similar in both groups during the follow-up. The percentage of delayed graft
      function was the only significant difference between both groups (NHB group 62%
      vs. HB group 32%; P=0.0001). Delayed graft function, in the NHB group, is
      influenced by the warm ischemia time, which is directly related to the number of
      days to achieve a serum creatinine<300 mmol/L (P=0.0001). The best cut-off times
      in this group were 45 min for warm ischemia time and 22 hr for cold ischemia
      time. Recipients have a greater likelihood of losing the graft beyond those
      limits (P=0.017, relative risk: 7.3). The incidence of acute rejection was
      similar in both groups, and it was the only predictor factor of graft loss in the
      complete series of patients (P=0.0001), in the NHB group (P=0.007), and in the HB
      group (P=0.02). CONCLUSIONS: Reducing the incidence of acute rejection and
      shortening ischemia time are conditions needed to guarantee a long graft survival
      of kidneys from NHB donors.

PMID- 9645806
TI  - Clinical significance of viral load in the diagnosis of cytomegalovirus disease
      after liver transplantation.
AB  - In a cohort of 43 liver transplant recipients who did not receive antiviral
      prophylaxis, qualitative and quantitative polymerase chain reactions (PCRs) from
      peripheral blood were prospectively compared to determine their value in the
      diagnosis of established cytomegalovirus (CMV) disease and for the early
      detection of CMV replication as a marker for preemptive antiviral therapy. Using
      a cutoff of 7000 copies of CMV DNA per sample, the specificity and positive
      predictive values of qualitative PCR for the diagnosis of established CMV disease
      increased from 33% to 89% and from 54% to 82%, respectively, without reducing the
      100% sensitivity and negative predictive value. By contrast, quantification of
      viral load provided no additional advantage to qualitative PCR for the early
      diagnosis of CMV infection before development of disease.

PMID- 9645805
TI  - Long-term results of triple-drug-based immunosuppression in nonneonatal pediatric
      heart transplant recipients.
AB  - BACKGROUND: Few reports document long-term results of pediatric cardiac
      transplantation in which triple therapy (cyclosporine, azathioprine, and
      corticosteroids) was the mainstay of immunosuppression. This report details a
      single center's pediatric transplant experience and analyzes the relative
      contributions of selected pre/posttransplant risk factors on long-term morbidity
      and mortality. METHODS: Retrospective data were collected for all non-neonatal
      pediatric transplant recipients including: presenting diagnosis, cardiac
      hemodynamics (particularly pulmonary vascular resistance index), donor ischemic
      time, occurrence of postoperative infections, episodes of allograft rejection,
      incidence of posttransplant lymphoproliferative disease or coronary artery
      disease (CAD), and overall survival. Analysis of single variables and a Cox
      proportional hazards model were utilized to determine the impact of
      pre/posttransplant risk factors on long-term survival. RESULTS: From 1984 to
      1995, 64 patients (mean age, 8.3 years), 46 of whom had cardiomyopathy and 18 who
      had inoperable complex congenital heart disease, underwent cardiac
      transplantation and received triple-drug immunosuppression. Orthotopic
      transplantation was performed unless the pulmonary vascular resistance index
      remained >6 um2 (despite use of pulmonary vasodilator). One patient required
      heterotopic transplantation. Average donor ischemic time was 217 min. An average
      of 1.2 rejection episodes/patient occurred (average follow-up period: 50 months).
      No patient developed posttransplant lymphoproliferative disease, but 22 patients
      (34%) developed CAD. Overall survival was 80%, 60%, and 57% at 1, 5, and 10
      years, respectively. Of outcome variables analyzed, rejection frequency was
      significantly increased in patients who subsequently developed CAD, but the
      presence of CAD was not significantly correlated with mortality. CONCLUSION:
      Triple-drug-based immunosuppressive maintenance therapy in pediatric heart
      transplant recipients results in good long-term graft survival.

PMID- 9645807
TI  - Partial T-cell activation and anergy induction by polyclonal antithymocyte
      globulin.
AB  - BACKGROUND: Polyclonal antithymocyte globulins have been assumed to deplete or
      sequester immunocompetent T cells. We investigated the hypothesis that anti-human
      thymocyte globulin (ATGAM)-mediated immunosuppression is delivered via
      nondepletive, immunologically specific actions as a consequence of simultaneous
      engagement of multiple T cell receptors. METHODS: Purified T cells obtained from
      healthy volunteers or renal transplant recipients receiving their first dose of
      ATGAM were evaluated for proliferative responses and cell-mediated lympholysis.
      ATGAM binding and receptor expression were determined by flow cytometry.
      Cytokines and ATGAM levels were measured by enzyme-linked immunosorbent assay.
      RESULTS: ATGAM-treated T cells showed significant dose-dependent inhibition of
      proliferation in vitro at concentrations comparable to those measured in
      patients. Effectors raised after ATGAM treatment failed to develop cytotoxicity.
      Supernatant interleukin (IL)-2 levels in ATGAM-treated cultures were
      significantly reduced (P<0.01 vs. control). IL-4 was not significantly altered.
      In vivo studies confirmed significant ATGAM-mediated inhibition of proliferative
      responses. Concanavalin A and OKT3-driven proliferation were reduced 30-60% by
      ATGAM. Flow cytometry showed that ATGAM recognized multiple cell surface
      receptors and resulted in markedly increased IL-2R and CD28 expression in the
      absence of proliferation, demonstrating partial T-cell activation. ATGAM
      synergized with phorbol myristate acetate to produce strong proliferation, which
      suggests that it provides a calcium-based signal resulting in anergy.
      CONCLUSIONS: ATGAM recognizes and cross-links multiple cell surface receptors and
      costimulator molecules on human T cells. Simultaneous engagement by ATGAM in the
      context of allogeneic or mitogenic stimulation leads to partial T-cell activation
      and anergy.

PMID- 9645808
TI  - Contribution of donor-specific antibodies to acute allograft rejection: evidence
      from B cell-deficient mice.
AB  - BACKGROUND: The role of T lymphocytes in acute allograft rejection is well
      established. The involvement of B lymphocytes in this process, however, is more
      controversial. A series of reports showed that mice without a functional B-cell
      compartment rejected allografts with the same kinetics as control animals. In
      rats, however, alloantibodies were found to play a decisive role in allograft
      rejection. To provide an explanation for the discrepant results, we readdressed
      the role of B cells and antibodies in mice with disrupted immunoglobulin mu chain
      genes. The use of cyclosporine (CsA), which strongly suppresses T cells, allowed
      us to focus specifically on the function of B cells. METHODS: C57BL/6 mice
      rendered B cell deficient by targeted disruption of the immunoglobulin mu chain
      gene (referred to as microMT/microMT mice) and microMT/+ control mice with one
      functional mu chain were heterotopically transplanted with fully MHC-disparate
      BALB/c hearts. CsA was administered subcutaneously by Alzet osmotic pumps. Normal
      and immune serum specific for donor hearts was given to assess the role of
      antibodies in the rejection process. RESULTS: Both B cell-deficient
      microMT/microMT and heterozygous microMT/+ mice were found to reject transplanted
      hearts within a similar period of time. In contrast, when T cells were partially
      suppressed with CsA, graft survival was significantly prolonged in
      microMT/microMT mice as compared with heterozygous controls. Passive transfer of
      donor-specific immune serum, obtained from microMT/+ animals rejecting allogeneic
      hearts, to CsA-treated microMT/microMT mice significantly accelerated allograft
      rejection as opposed to recipients treated with normal serum. CONCLUSIONS: B
      lymphocytes and antibodies play an important role in acute allograft rejection
      particularly when the dominant T-cell compartment is partially suppressed.

PMID- 9645809
TI  - Posttransplant liver granulomatosis associated with hepatitis C?
AB  - BACKGROUND: Liver granulomatosis is an occasional finding in posttransplant liver
      biopsies. Its diagnosis is made more difficult by the variety of conditions that
      can lead to it. In the nontransplant setting, the association of liver
      granulomatosis and hepatitis C virus (HCV) infection has occasionally been
      described. METHODS: We describe the case of a patient with a liver
      transplantation for an HCV-associated cirrhosis who developed an alteration of
      liver tests. Granulomatosis was detected on the liver biopsy. RESULTS: Other
      causes of granulomatosis were satisfactorily excluded. The development of the
      lesions coincided with a viral flare-up. CONCLUSION: We think that HCV can be
      listed among the possible causes of liver granulomas in the posttransplant
      setting and that it must be considered in the differential diagnosis of this
      condition.

PMID- 9645810
TI  - Domino hepatic transplantation using the liver from a patient with familial
      amyloid polyneuropathy.
AB  - BACKGROUND: In transplantation, novel methods are required to augment the supply
      of donor organs. We report the first domino liver transplant in which a patient
      with familial amyloid polyneuropathy (FAP) received an orthotopic split liver
      graft, and her explanted liver was donated to another patient. Three successful
      liver transplants were thus achieved from the one cadaver liver. PATIENTS AND
      METHODS: A cadaveric donor liver was split and the left lobe was grafted into a
      child with biliary atresia. The right lobe was transplanted into a woman with FAP
      associated with the transthyretin Met30 variant. Her own otherwise healthy liver
      was donated to a patient with cirrhosis and hepatocellular carcinoma. RESULTS:
      Fifteen months after transplantation, all three recipients are well with normal
      liver function. The domino recipient developed inferior vena cava stricturing at
      the level of anastomosis after surgery with resultant ascites, requiring
      dilatation and LeVeen shunt insertion. Serum amyloid P component scintigraphy
      showed amyloid regression in the domino donor and to date has not identified any
      amyloid deposits in the recipient, who also remains free of tumor recurrence.
      CONCLUSIONS: Domino transplantation using the livers from patients with FAP may
      be justified for patients whose disease condition precludes a long spell on the
      waiting list, including those with hepatic malignancies and those for whom
      palliation rather than long-term cure is the aim.

PMID- 9645811
TI  - Efficacy of lamivudine re-treatment in a patient with hepatitis B virus (HBV)
      recurrence after liver transplantation and HBV-DNA breakthrough during the first
      treatment.
AB  - BACKGROUND: Transplantation for terminal hepatitis B virus (HBV) disease is
      aggravated by a high rate of reinfection and disease recurrence. Lamivudine, a
      new nucleoside analog, is a potent inhibitor of HBV synthesis, but its use may
      lead to the emergence of HBV-DNA polymerase mutants resistant to the drug.
      METHODS AND RESULTS: We describe the case of a patient who developed an HBV
      recurrence after liver transplantation and was treated with lamivudine. An HBV
      DNA breakthrough occurred 7 months after the start of therapy, and the drug was
      stopped after 9 months. The molecular state of HBV-DNA was analyzed, and a
      mutation in the YMDD (tyrosine, methionine, aspartate, aspartate) locus of HBV
      DNA polymerase was identified. Nine months after the suspension of lamivudine the
      patient experienced a new hepatic attack accompanied by high HBV-DNA levels.
      Lamivudine was given again. Serum HBV-DNA levels normalized after 45 days of re
      treatment, but lamivudine-resistant mutants were again the prevalent viral
      population after 3 months. CONCLUSIONS: The case described suggests that
      retherapy with lamivudine after a first emergence of YMDD mutants is temporarily
      effective in recontrolling HBV synthesis but ultimately induces the accelerated
      reemergence of a prevalently mutant population of HBV. This emphasizes the need
      for combined antiviral therapy.

PMID- 9645812
TI  - Pathogenesis of early operative site infections after orthotopic liver
      transplantation.
AB  - BACKGROUND: We hypothesized that operative site infections after orthotopic liver
      transplantation arise from bacteria in bile or jejunum. METHODS: To ascertain the
      validity of this hypothesis and to assess the effect of systemic antibiotic
      prophylaxis, we obtained intraoperative cultures of peritoneum, fascia, explant
      and donor liver bile, and jejunal lumen in 77 liver transplantations, and we
      monitored outcome. RESULTS: Pathogens were recovered from peritoneum, fascia, or
      bile in 11 cases. By univariate analysis, a positive culture was significantly
      associated with choledochojejunostomy (P=0.0002), previous liver transplantation
      (P=0.0002), and previous hepatobiliary surgery (P=0.002). Operative site
      infections during the first 2 weeks after transplantation occurred only in cases
      with positive intraoperative cultures, and three of the four infections were
      caused by the same bacteria detected intraoperatively. Antibiotic susceptibility
      of intraoperative isolates was tested in nine cases; infection occurred in two of
      three cases in which the isolates were resistant to the systemic antibiotic
      prophylaxis and in none of six cases with susceptible isolates. CONCLUSIONS: Our
      findings suggest that systemic antibiotic prophylaxis for more than 2 days may be
      beneficial in cases with bacterial contamination of the operative site but may
      not be necessary in other cases.

PMID- 9645813
TI  - Mycophenolate mofetil in renal transplant recipients with cyclosporine-associated
      nephrotoxicity: a preliminary report.
AB  - BACKGROUND: There is a great concern over cyclosporine (CsA) nephrotoxicity in
      renal transplant recipients, and the effects of conversion from CsA to
      azathioprine (AZA) remain controversial. Large studies have demonstrated that
      mycophenolate mofetil (MMF), the morpholinoethyl ester of mycophenolic acid, is
      superior to AZA as a posttransplant immunosuppressant. METHODS: Six patients with
      isolated biopsy-proven CsA nephrotoxicity were converted from CsA-AZA to MMF.
      RESULTS: Mean follow-up was 12+/-2 months. No patient experienced acute
      rejection. The mean serum creatinine concentration decreased from 225+/-58 to
      159+/-66 micromol/L (P<0.0005). Hyperlipidemia and blood pressure improved after
      CsA withdrawal. CONCLUSION: In a selected transplant population with biopsy
      proven CsA nephrotoxicity, CsA withdrawal with a concomitant switch from AZA to
      MMF seems to be safe and allows a significant improvement of renal function.

PMID- 9645814
TI  - Histologic features of chronic allograft nephropathy revealed by protocol
      biopsies in kidney transplant recipients.
AB  - BACKGROUND: The aim of the present study was to describe the histologic features
      disclosed by protocol kidney transplant biopsies in patients who experienced
      neither acute rejection nor acute renal failure during the 2 years after
      transplantation. METHODS: We studied 10 recipients of HLA-identical kidneys from
      living-related donors and 31 recipients of cadaveric kidneys. They were selected
      because, during the 2 years after transplantation, they did not experience
      clinical acute or chronic rejection, their renal function was normal and stable,
      and they underwent a protocol kidney biopsy at 3 months and at 2 years after
      transplantation. RESULTS: Histologic chronic allograft nephropathy was present in
      25% of patients at 3 months and in 50% at 2 years, but was absent in the
      recipients of HLA-identical kidneys. Histologic worsening was associated with
      increased donor age, the presence of asymptomatic grade I acute rejection at 3
      months, and an increased cyclosporine trough level. CONCLUSIONS: Protocol
      biopsies contribute important information that could be used to improve the
      prophylaxis of chronic allograft nephropathy.

PMID- 9645815
TI  - Successful long-term kidney-pancreas transplants in diabetic patients with high C
      peptide levels.
AB  - BACKGROUND: Pancreas transplants are rarely done in type 2 (noninsulin dependent)
      diabetic patients. Most researchers believe that in type 2 diabetic patients,
      peripheral insulin resistance plays a central role and also is associated with
      relative insulin deficiency or an insulin secretory defect. This suggests that in
      patients receiving transplants, the new beta cells will be overstimulated,
      leading to beta cell "exhaustion" and graft failure. METHODS: Early in our
      experience, simultaneous pancreas-kidney transplant candidates were selected
      using only clinical criteria for type 1 diabetes, i.e., early onset of diabetes
      and rapid onset of insulin use. Pretransplant sera were available for C-peptide
      analysis in 70 of 94 of those patients. Forty-four percent (31/70) were African
      American (AA). RESULTS: Thirteen patients (12 AA) with a nonfasting C-peptide
      level >1.37 ng/ml were identified. In these patients with high C-peptide levels,
      pancreas and kidney survival rates were 10O%. The results did not differ
      statistically from the low C-peptide group (< or =1.37 ng/ ml). There were no
      differences between patient and pancreas-kidney survival rates when the patients
      were separated into AA and non-AA groups. The follow-up was 1-89 months, with a
      mean of 45.5 months. CONCLUSIONS: Long-term pancreas graft function is attainable
      and beta cell "exhaustion" does not occur in patients with high preoperative C
      peptide (>1.37 ng/ ml) levels. AA and non-AA patients have equivalent long-term
      patient, kidney, and pancreas-kidney graft survival rates.

PMID- 9645816
TI  - Increased CD40 ligand gene expression during human renal and murine islet
      allograft rejection.
AB  - BACKGROUND: The interaction between CD40 and its ligand CD40L is essential for
      the development and maintenance of vigorous immunity. We have sought to
      determine: (i) whether a heightened level of CD40L transcripts is evident during
      acute allograft rejection and (ii) the kinetics of CD40L gene expression during
      allograft rejection. METHODS: By using quantitative reverse transcriptase
      assisted polymerase chain reaction techniques, we found that heightened CD40L
      gene expression is a correlate of acute human renal allograft rejection (P<0.01).
      RESULTS: In a murine model of MHC-mismatched islet allografts, our results showed
      that CD40L transcripts were rarely detected at day 2 after transplantation, but
      were remarkably heightened at day 5 after transplantation. The transcript levels
      then steadily increased and peaked at the time of rejection. CONCLUSION: These
      data suggest that therapy aimed at blocking the CD40 to CD40L interaction should
      be applied during the immediate posttransplant period.

PMID- 9645817
TI  - Xenoantibodies to pig endothelium are expressed in germline configuration and
      share a conserved immunoglobulin VH gene structure with antibodies to common
      infectious agents.
AB  - BACKGROUND: The rejection of pig xenografts in humans is initiated by preformed
      antibodies that may be related to the natural antibodies that formulate a first
      line of defense against infectious agents. Immunoglobulin gene variable domains
      encoding the antibodies that react with similar epitopes expressed on
      xenoantigens and bacteria may share structurally similar antigen-binding site
      configurations. METHODS: We sequenced the VH immunoglobulin genes and germline
      progenitors of two rat monoclonal antibodies that recognize pig xenoantigens.
      Nucleic and amino acid sequences of these xenoantibodies were compared with
      immunoglobulin genes encoding antibodies that react with bacteria or viruses.
      RESULTS AND CONCLUSIONS: VH genes encoding rat anti-pig xenoantibodies are
      expressed in germline configuration and share structural similarities, including
      identical amino acids in key antigenic contact sites that define antibody
      canonical structural groups, with antibodies to infectious agents.

PMID- 9645818
TI  - HLA class I and class II antibodies: monitoring before and after kidney
      transplantation and their clinical relevance.
AB  - BACKGROUND: In search of an alternative screening technique, we compared
      complement-dependent cytotoxicity (CDC) with PRA-STAT, a commercially available
      enzyme-linked immunosorbent assay (ELISA). METHODS: A total of 188 pre- and
      posttransplant sera from 50 renal allograft recipients were tested with both
      methods. RESULTS: A significant correlation was found between both methods.
      Discrepant results could be explained by the fact that PRA-STAT detects both HLA
      class I and II antibodies (while CDC with peripheral blood lymphocytes as target
      cell detects mainly HLA class I reactivity), by the presence of IgM antibodies
      (which are not detected by the IgG-specific ELISA test), and by CDC "false
      positive" results due to antibody rejection treatment. The clinical relevance of
      antibodies detected by PRA-STAT is suggested by the following. (a) In eight
      patients, donor-specific HLA antibodies detected by PRA-STAT (but not seen by
      CDC) resulted in severe rejection episodes, which led to graft loss in four
      cases. In all but one patient, antibodies were directed against class II or
      mixtures of class I and H antigens. Six patients with complications were shown to
      have developed de novo antibodies against DQ incompatibilities. (b) Half of the
      patients with a positive ELISA test at the moment of crossmatch experienced
      complications. Such patients are at a threefold higher risk of suffering from
      rejection episodes and/or graft loss than patients who are not sensitized
      (P<0.05, Fisher exact test). CONCLUSIONS: Because PRA-STAT is very reproducible,
      detects both HLA class I and II antibodies, and is not influenced by rejection
      therapy, we consider it an additional tool for pre- and posttransplant monitoring
      of kidney allograft recipients.

PMID- 9645819
TI  - Pulmonary infection caused by Rhodococcus equi in a kidney and pancreas
      transplant recipient: a case report.

PMID- 9645820
TI  - Comment on "Persistent long-term changes in lymphocyte subsets induced by
      polyclonal antibodies" by Muller et al.

PMID- 9645821
TI  - Noninvasive metabolic assessment of human donor livers: metabolite assignment in
      31P magnetic resonance spectroscopy.

PMID- 9645822
TI  - The importance of reaching preconception targets for glycemic control in diabetic
      women.

PMID- 9645823
TI  - Hyperhomocysteinemia and atherosclerotic vascular disease: pathophysiology,
      screening, and treatment. off.
AB  - Hyperhomocysteinemia has recently been identified as an important risk factor for
      atherosclerotic vascular disease. This article reviews homocysteine metabolism,
      causes of hyperhomocysteinemia, the pathophysiological findings of this disorder,
      and epidemiological studies of homocysteine and vascular disease. Screening for
      hyperhomocysteinemia should be considered for patients at high risk for vascular
      disease or abnormalities of homocysteine metabolism. For primary prevention of
      vascular disease, treatment of patients with homocysteine levels of 14 micromol/L
      or higher should be considered. For secondary prevention, treatment of patients
      with homocysteine levels of 11 micromol/L or higher should be considered.
      Treatment is most conveniently administered as a folic acid supplement (400-1000
      microg) and a high-potency multivitamin that contains at least 400 microg of
      folate. Higher doses of folic acid and cyanocobalamin supplements may be required
      in some patients. Until prospective clinical trial data become available, these
      conservative recommendations provide a safe, effective, and evidence-based
      approach to the diagnosis, evaluation, and management of patients with
      hyperhomocysteinemia.

PMID- 9645824
TI  - Klinefelter syndrome.
AB  - Klinefelter syndrome is the most common sex chromosome disorder. Affected males
      carry an additional X chromosome, which results in male hypogonadism, androgen
      deficiency, and impaired spermatogenesis. Some patients may exhibit all of the
      classic signs of this disorder, including gynecomastia, small testes, sparse body
      hair, tallness, and infertility, whereas others, because of the wide variability
      in clinical expression, lack many of these features. Treatment consists of
      testosterone replacement therapy to correct the androgen deficiency and to
      provide patients with appropriate virilization. This therapy also has positive
      effects on mood and self-esteem and has been shown to protect against
      osteoporosis, although it will not reverse infertility. Although the diagnosis of
      Klinefelter syndrome is now made definitively using chromosomal karyotyping,
      revealing in most instances a 47,XXY genotype, the diagnosis also can be made
      using a careful history and results of a physical examination, with the hallmark
      being small, firm testes. As it affects 1 in 500 male patients and presents with
      a variety of clinical features, primary care physicians should be familiar with
      this condition.

PMID- 9645825
TI  - Echocardiographic predictors of stroke in patients with atrial fibrillation: a
      prospective study of 1066 patients from 3 clinical trials.
AB  - BACKGROUND: Clinical features that consistently predict ischemic stroke in
      patients with nonvalvular atrial fibrillation have been identified, while
      echocardiographic risk factors are less well defined. OBJECTIVE: To determine
      whether the results of transthoracic echocardiography add independent information
      to the clinical risk factors for stroke in patients with atrial fibrillation.
      METHODS: Transthoracic echocardiographic findings and clinical features from 1066
      patients with atrial fibrillation assigned to placebo or control in 3 randomized
      trials (Boston Area Anticoagulation Trial for Atrial Fibrillation, Stroke
      Prevention in Atrial Fibrillation I Study, and Veterans Affairs Prevention in
      Atrial Fibrillation Study) were correlated with subsequent ischemic stroke by
      multivariate analysis. RESULTS: The mean + SD age of patients was 67 +/- 10
      years, 78% were men, 55% had a history of hypertension, 19% had a history of
      diabetes, 7% had a previous transient ischemic attack or stroke, and 27% had a
      history of heart failure. During a mean follow-up of 1.6 years, 78 ischemic
      strokes occurred (annual rate, 4.7%). Moderate to severe left ventricular
      systolic dysfunction shown via 2-dimensional echocardiography was a strong
      independent predictor of stroke (relative risk, 2.5; P<.001) in the 1010 patients
      in whom echocardiographic values for left ventricular function were available.
      Left atrial diameter by M-mode echocardiography did not predict stroke (relative
      risk, 1.02/mm; P = .10). Of 163 patients categorized as low risk based on
      clinical features (annual stroke rate, 0.8%; 95% confidence interval, 0.2%-3.0%),
      10 had moderate to severe left ventricular dysfunction shown via 2-dimensional
      echocardiography and a 9.3% per year risk of stroke (95% confidence interval,
      1.3%-66%). Conversely, 728 of the 847 patients at high risk for stroke based on
      clinical criteria had normal or mildly abnormal left ventricular function; their
      stroke rate was 4.4% (95% confidence interval, 3.4%-5.8%). CONCLUSIONS: Left
      ventricular systolic dysfunction shown via 2-dimensional transthoracic
      echocardiography independently predicts risk of stroke in patients with atrial
      fibrillation. Echocardiography may prove most useful in a small group of patients
      who have a low risk of stroke according to clinical factors.

PMID- 9645826
TI  - Factors influencing preconception control of glycemia in diabetic women.
AB  - BACKGROUND: Although periconceptional glycemic control directly impacts perinatal
      outcome for pregestational diabetic women, these women still frequently enter
      pregnancy with suboptimal control of glycemia. OBJECTIVES: To determine how
      frequently diabetic women enter pregnancy with suboptimal glycemic control and to
      identify factors associated with not achieving optimal periconceptual control of
      glycemia. PATIENTS AND METHODS: Pregestational diabetic women (n = 55) who
      attended the Maternal Fetal Medicine Faculty Practice or the Resident Medical
      Complications Obstetric Clinic, Magee Women's Hospital, Pittsburgh, Pa, were
      administered a brief questionnaire pertaining to periconceptional education and
      control of glycemia. Levels of periconceptional hemoglobin A1c, were measured in
      all patients. RESULTS: Sixty-one percent of pregestational diabetic women
      presented for prenatal care with suboptimal control of their blood glucose levels
      (hemoglobin A1c measurement, >0.08). Of the 55 diabetic women who participated in
      the questionnaire, 47 (86%) were under the care of a physician for their
      diabetes, 45 (82%) monitored their glucose level at least 3 times per day, 34
      (60%) stated that they had been advised to plan a pregnancy, and 29 (53%) stated
      that they had planned their pregnancies. Women who had not been advised to
      achieve target hemoglobin A1c levels were more likely to enter pregnancy with
      suboptimal control of their blood glucose levels (P = .02). Women who experienced
      prior complications with pregnancy were significantly more likely to enter
      pregnancy with suboptimal control of their blood glucose levels (P = .02).
      CONCLUSIONS: Diabetic women frequently enter pregnancy with suboptimal control of
      glycemia. Women not advised to achieve target glucose or hemoglobin A1c levels
      were more likely to enter pregnancy with suboptimal control of glycemia.

PMID- 9645827
TI  - Preinfarction blood pressure and smoking are determinants for a fatal outcome of
      myocardial infarction: a prospective analysis from the Finnmark Study.
AB  - BACKGROUND: Serum cholesterol levels, blood pressure, and smoking are the classic
      coronary risk factors, but what determines whether a myocardial infarction will
      be fatal or not? OBJECTIVE: To investigate cardiovascular risk factors that may
      influence survival in subjects with coronary heart disease (myocardial infarction
      and sudden death). SUBJECTS AND METHODS: All inhabitants aged 35 to 52 years in
      Finnmark County, Norway, were invited to a cardiovascular survey in 1974-1975
      and/or 1977-1978. Attendance rate was 90.5%. A total of 6995 men and 6320 women
      were followed up for 14 years with regard to incident myocardial infarction and
      sudden death. Predictors for 28-day case fatality rate after first myocardial
      infarction were analyzed. RESULTS: During 186 643 person-years, 635 events among
      men and 125 events among women were registered. The case fatality rate was 31.6%
      in men and 28.0% in women (P =.50). Among men (women) with baseline systolic
      blood pressure lower than 140 mm Hg, the 28-day case fatality rate was 24.5%
      (22.6%), among those with systolic blood pressure of 140 through 159 mm Hg, the
      case fatality rate was 35.6% (28.2%), and among those with systolic blood
      pressure of 160 mm Hg or higher, the case fatality rate was 48.2% (41.7%). Of the
      760 subjects with myocardial infarction, 348 died during follow-up. In Cox
      regression analysis, systolic blood pressure at baseline was strongly related to
      death (relative risk per 15 mm Hg, 1.22; 95% confidence interval, 1.13-1.31).
      Daily smoking at baseline (relative risk, 1.40; 95% confidence interval, 1.07
      1.85) and age at time of event (relative risk per 5 years, 1.12; 95% confidence
      interval, 1.01-1.24) were additional significant risk factors, while total serum
      and high-density lipoprotein cholesterol levels were unrelated to survival.
      Similar results were obtained with diastolic blood pressure in the model.
      CONCLUSIONS: Preinfarction blood pressure was an important predictor of case
      fatality rate in myocardial infarction. Daily smoking and age were additional
      significant predictors.

PMID- 9645828
TI  - Obesity without sleep apnea is associated with daytime sleepiness.
AB  - BACKGROUND: Daytime sleepiness and fatigue is a frequent complaint of obese
      patients even among those who do not demonstrate sleep apnea. OBJECTIVE: To
      assess in the sleep laboratory whether obese patients without sleep apnea are
      sleepier during the day compared with healthy controls with normal weight.
      METHODS: Our sample consisted of 73 obese patients without sleep apnea, upper
      airway resistance syndrome, or hypoventilation syndrome who were consecutively
      referred for treatment of their obesity and 45 controls matched for age. All
      patients and healthy controls were monitored in the sleep laboratory for 8 hours
      at night and at 2 daytime naps, each for 1 hour the following day. RESULTS: Obese
      patients compared with controls were sleepier during the day and their nighttime
      sleep was disturbed. During both naps, sleep latency, wake time after onset of
      sleep, and total wake time were significantly lower, whereas the percentage of
      sleep time was significantly higher in obese patients compared with controls. In
      contrast, during the nighttime testing, obese patients compared with controls
      demonstrated significantly higher wake time after onset of sleep, total wake
      time, and lower percentage of sleep time. An analysis of the relation between
      nighttime and daytime sleep suggested that daytime sleepiness in obese patients
      is a result of a circadian abnormality rather than just being secondary to
      nighttime sleep disturbance. CONCLUSIONS: Daytime sleepiness is a morbid
      characteristic of obese patients with a potentially significant impact on their
      lives and public safety. Daytime sleepiness in individuals with obesity appears
      to be related to a metabolic and/or circadian abnormality of the disorder.

PMID- 9645829
TI  - Diuretic-based treatment and cardiovascular events in patients with mild renal
      dysfunction enrolled in the systolic hypertension in the elderly program.
AB  - BACKGROUND: It is expected that the treatment of hypertension in patients with
      renal disease decreases the risk of cardiovascular events, but the evidence in
      these patients is lacking. OBJECTIVE: To assess the effect of diuretic-based
      treatment on cardiovascular events in patients with isolated systolic
      hypertension and renal dysfunction. METHODS: A total of 4336 persons aged 60
      years and older with systolic blood pressures of 160 mm Hg and higher and
      diastolic blood pressures of less than 90 mm Hg were randomly assigned to receive
      either placebo or chlorthalidone (12.5-25.0 mg/d), with the addition of atenolol
      (25-50 mg/d) or reserpine (0.05-0.10 mg/d) if needed, and observed for 5 years.
      The risk of first-occurring cardiovascular events, including stroke, transient
      ischemic attack, myocardial infarction, heart failure, coronary artery bypass
      surgery, angioplasty, aneurysm, endarterectomy, sudden death, or rapid death, was
      stratified according to baseline serum creatinine levels (35.4-84.0, 84.1-101.6,
      101.7-119.3, and 119.4-212.2 micromol/L [0.4-0.9, 1.0-1.1, 1.2-1.3, and 1.4-2.4
      mg/dL]). RESULTS: Systolic blood pressure reduction was not affected by baseline
      serum creatinine levels. Active treatment did not affect the risk of serum
      creatinine levels becoming elevated during follow-up. The risk of hypokalemia
      with active treatment decreased significantly with increasing baseline serum
      creatinine levels. In the 4 baseline serum creatinine groups, the relative risk
      (95% confidence interval) of cardiovascular events developing with active
      treatment was 0.73 (0.54-0.97), 0.63 (0.49-0.82), 0.62 (0.44-0.87), and 0.59
      (0.38-0.91). The results were similar for the outcomes of stroke or coronary
      artery events and in analyses stratified by sex or age. CONCLUSION: Diuretic
      based treatment of patients with isolated systolic hypertension prevents the
      development of cardiovascular events in older persons with mild renal
      dysfunction.

PMID- 9645830
TI  - Safely increasing the proportion of patients with community-acquired pneumonia
      treated as outpatients: an interventional trial.
AB  - BACKGROUND: Patients with community-acquired pneumonia who are at low risk for
      short-term mortality can be identified using a validated prediction rule, the
      Pneumonia Severity Index. Such patients should be candidates for outpatient
      treatment, yet many are hospitalized. OBJECTIVE: To assess a program to safely
      increase the proportion of low-risk patients with pneumonia treated at home.
      METHODS: The intervention provided physicians with the Pneumonia Severity Index
      score and corresponding mortality risk for eligible patients and offered enhanced
      visiting nurse services and the antibiotic clarithromycin. Prospectively
      enrolled, consecutive low-risk patients with pneumonia presenting to an emergency
      department during the intervention period (n = 166) were compared with
      consecutive retrospective controls (n = 147) identified during the prior year. A
      second group of 208 patients from the study hospital who participated in the
      Pneumonia Patient Outcomes Research Team cohort study served as controls for
      patient-reported measures of recovery. RESULTS: There were no significant
      baseline differences between patients in the intervention and control groups. The
      percentage initially treated as outpatients increased from 42% in the control
      period to 57% in the intervention period (36% relative increase; 95% confidence
      interval, 8%-72%; P = .01). However, more outpatients during the intervention
      period were subsequently admitted to the study hospital (9% vs 0%). When any
      admission to the study hospital within 4 weeks of presentation was considered,
      there was a trend toward more patients receiving all their care as outpatients in
      the intervention group (42% vs 52%; 25% relative increase; 95% confidence
      interval -2% to 59%; P = .07). No patient in the intervention group died in the 4
      week follow-up period. Symptom resolution and functional status were not
      diminished. Satisfaction with overall care was similar, but patients treated in
      the outpatient setting during the intervention were less frequently satisfied
      with the initial treatment location than comparable control patients (71% vs 90%;
      P = .04). CONCLUSIONS: Use of a risk-based algorithm coupled with enhanced
      outpatient services effectively identified low-risk patients with community
      acquired pneumonia in the emergency department and safely increased the
      proportion initially treated as outpatients. Outpatients in the intervention
      group were more likely to be subsequently admitted than were controls, lessening
      the net impact of the intervention.

PMID- 9645831
TI  - Physical examination and chronic lower-extremity ischemia: a critical review.
AB  - OBJECTIVE: To determine the clinical utility of physical examination in patients
      with suspected chronic ischemia of the lower extremities. DATA SOURCES: MEDLINE
      search (January 1966 to January 1997), personal files, and bibliographies of
      textbooks on physical diagnosis, surgery, and vascular surgery. STUDY SELECTION:
      Both authors independently graded the studies as level 1, 2, or 3, according to
      predetermined criteria. Criteria deemed essential for analysis of sensitivity,
      specificity, and likelihood ratios were (1) clear definition of study population,
      (2) clear definition of physical examination maneuver, and (3) use of an
      acceptable criterion standard test for comparison. RESULTS: The following
      positive findings help clinicians diagnose the presence of peripheral arterial
      disease: abnormal pedal pulses, a unilaterally cool extremity, a prolonged venous
      filling time, and a femoral bruit. Other physical signs help determine the extent
      and distribution of vascular disease, including an abnormal femoral pulse, lower
      extremity bruits, warm knees, and the Buerger test. The capillary refill test and
      the findings of foot discoloration, atrophic skin, and hairless extremities are
      unhelpful in diagnostic decisions. Mathematical formulas, derived from 2 studies
      using multivariate analysis, allow clinicians to estimate the probability of
      peripheral arterial disease in their patients. CONCLUSION: Certain aspects of the
      physical examination help clinicians make accurate judgments about the presence
      of peripheral arterial disease and its distribution.

PMID- 9645832
TI  - Globus sensation: pharyngoesophageal function, psychometric and psychiatric
      findings, and follow-up in 88 patients.
AB  - BACKGROUND: The globus sensation has been widely regarded as psychogenic, but
      organic disorders were found to be etiologically significant. OBJECTIVE: To
      investigate the structural, functional, psychological, and psychiatric factors
      possibly eliciting the globus sensation and influencing its course. METHODS:
      Eighty-eight patients, 67 women and 21 men (aged 22-71 years), referred to 2
      tertiary care centers underwent history taking, otolaryngological examination,
      pharyngoesophageal videofluoroscopy and manometry, psychosocial evaluation,
      psychometric tests, psychiatric interview, and when indicated,
      esophagogastroduodenoscopy, esophageal bolus transport, gastroesophageal reflux,
      and gastric emptying studies. According to revealed disorders, therapy was
      initiated, and the outcome was studied. RESULTS: Only 15 patients had normal
      pharyngoesophageal function; of these 15, 6 had chronic tonsillitis or
      pharyngitis, 3 had thyroid adenomata, 4 had cervical spondylosis, and 1 each had
      dry oropharyngeal mucosa and chronic bronchitis. Of the other 73 patients, 2 had
      pharyngeal dysfunction, 24 had achalasia, 1 had diffuse esophageal spasms, 3 had
      "nutcracker esophagus," 30 had nonspecific esophageal motor disorders, and 13 had
      gastroesophageal reflux. Psychometry revealed no more anxiety and depression than
      in general medical outpatients. Of 58 patients interviewed, 37 met criteria for
      psychiatric disorders. Psychometric scores and psychiatric characteristics were
      unrelated to the sensation's course. Therapy was recommended, but only 26
      patients were treated accordingly; 22 received nonspecific treatment. Follow-up 3
      to 59 months later revealed that the sensation had vanished in 13 patients who
      had received specific treatment, 5 who had received nonspecific treatment, and 6
      who had received no treatment; it was alleviated in 10 who had received specific
      treatment, 13 who had received nonspecific treatment, and 9 who had received no
      treatment; and it was unchanged in 3 who had received specific treatment, 5 who
      had received nonspecific treatment, and 23 patients who had received no
      treatment. CONCLUSIONS: Pharyngoesophageal disorders may be sensed only vaguely,
      inducing the globus sensation. Psychological and psychiatric characteristics
      could be relevant to the discomfort experienced but are unlikely to be
      etiologically significant.

PMID- 9645833
TI  - What appears to be cancer.
AB  - We describe a case of multiple hepatic pyogenic abscesses with an unusual
      presentation. The typical signs and symptoms of fever and pain in the right upper
      quadrant were absent. Instead, the chief complaint was muscle weakness and
      myalgias accompanied by weight loss. Findings from an ultrasonogram of the
      abdomen revealed multiple hepatic lesions consistent with metastases. Hence, the
      initial presumptive diagnosis was metastatic malignancy with unknown primary
      tumor. It was only when purulent material was unexpectedly encountered when a
      needle biopsy was performed that the true diagnosis of pyogenic liver abscess was
      recognized. While liver abscess is rare, it should not be forgotten in the
      differential diagnosis for multiple hepatic lesions seen on imaging studies.

PMID- 9645834
TI  - Pseudo-Meigs syndrome with elevated CA 125 levels.

PMID- 9645835
TI  - Sublingual nifedipine-induced anaphylaxis.

PMID- 9645836
TI  - Proton irradiation for non-small cell lung cancer.

PMID- 9645837
TI  - Antithymocyte globulin-induced adult respiratory distress syndrome.

PMID- 9645838
TI  - Esophageal stenosis and Graves disease in brittle type 1 diabetes mellitus.

PMID- 9645839
TI  - Pseudopheochromocytoma: an unrecognized cancer-associated syndrome?

PMID- 9645840
TI  - A method for the isolation of tegument syncytium mitochondria from Taenia
      crassiceps cysticerci and partial characterization of their aerobic metabolism.
AB  - Heterogeneous populations of mitochondria have been described in helminths.
      Mitochondria from different tissues have been isolated in adult organisms.
      However, in larvae, due to their small size, isolation from tissues has not been
      feasible. A method for the isolation of tegumental mitochondria from the larval
      stage of Taenia crassiceps is described. After solubilization of the plasma
      membrane with saponin, tegumental mitochondria were purified by a simple and
      rapid protocol of differential centrifugation, which allowed the retention of
      suitable quantities of well-preserved mitochondria, as judged by biochemical and
      ultrastructural parameters. Respiratory activity evoked by exogenous NADH was
      negligible, but its oxidation increased several-fold after sonication of intact
      mitochondria. Other substrates, e.g., succinate and malate-glutamate, were
      oxidized at high rate, leading to the formation of a H+ gradient across the inner
      mitochondrial membrane, which, in turn, supported oxidative phosphorylation.
      These results indicate that tegumental mitochondria carry out aerobic metabolism.

PMID- 9645842
TI  - Gastrointestinal helminths of loggerhead turtles (Caretta caretta) from the
      western Mediterranean: constraints on community structure.
AB  - Richness and composition of gastrointestinal helminth communities of 54
      loggerhead turtles, Caretta caretta, from the western Mediterranean were
      interpreted from patterns of helminth exchange at 2 host taxonomic scales:
      exchange between marine turtles and other marine hosts and exchange within
      turtles. We predicted exchange of the former to be unimportant ecologically and
      evolutionarily because of the host phylogenetic distance. The absence of records
      of successful exchange at this host taxonomic scale confirmed that host
      physiological barriers seem to prevent contemporary parasite transfer between
      marine turtles and other sympatric hosts. Marine turtles also seem to exhibit an
      evolutionary association with their parasites largely independent from that of
      other marine hosts. Therefore, the composition of gastrointestinal helminth
      communities of marine turtles is predictably restricted to digeneans, nematodes,
      and aspidogastreans specific to these reptiles. At the scale of host species,
      helminth exchange among marine turtle species was expected to be significant.
      This was suggested by reports indicating a high proportion of parasites common to
      all sea turtle species. Mediterranean C. caretta harbored only 4 digenean species
      typical of marine turtles, and immature individuals of 1 digenean species
      accidentally acquired. Further, no relevant parasite exchange with other marine
      turtles was expected to occur because C. caretta is the only sea turtle species
      abundant in the western Mediterranean. Therefore, a predictable composition
      coupled with low species richness in infracommunities might be accounted for
      partly by constraints on parasite acquisition at both host scales. Host factors
      limiting parasite recruitment (mainly ectothermy and a wandering behavior) may
      also contribute to depauperate and isolationist infracommunities.

PMID- 9645841
TI  - Increased excretion of aromatic amino acid catabolites in animals infected with
      Trypanosoma brucei evansi.
AB  - Aromatic amino acid catabolism by Trypanosoma brucei evansi was investigated in
      vivo using C3HeB/FeJ mice. The major catabolites detected by gas chromatography
      in the urines of infected animals were phenylpyruvic acid, 4-hydroxyphenylpyruvic
      acid, and indole-3-pyruvic acid. Identity of each compound was confirmed by gas
      chromatography-mass spectrometry. Concentrations of catabolites in urine of
      infected mice were correlated with parasitemia and returned to normal following
      suramin treatment. Other aromatic amino acid metabolites, including indole-3
      acetic acid, indole-3-lactic acid, and 4-hydroxyphenyllactic acid, were detected
      in urine from infected animals by gas chromatography mass spectrometry, although
      quantities were too low to be quantified reproducibly. Both phenylpyruvic acid
      and 4-hydroxyphenylpyruvic acid were also detected in urine of dogs and donkeys
      experimentally infected in Egypt with a recent field isolate of T. b. evansi.
      Tryptophan metabolites could not be assayed in dog and urine samples because
      formalin, which degraded the indole acids, had to be added before the samples
      could be imported into the U.S. Finally, concentrations of urinary catabolites
      during infection were correlated with the tyrosine aminotransferase activity in
      infected mouse sera.

PMID- 9645843
TI  - Ascaris lumbricoides intensity in relation to environmental, socioeconomic, and
      behavioral determinants of exposure to infection in children from southeast
      Madagascar.
AB  - Ascaris lumbricoides worm counts were examined as the outcome products of
      exposure proxy variables. A survey of 663 children, 4-10 yr old, living in
      southeastern Madagascar revealed prevalences of 93% for A. lumbricoides, 55% for
      Trichuris trichiura, and 27% for hookworm. Worm expulsions were conducted on 428
      of these children; the data revealed an overdispersed distribution of A.
      lumbricoides, with an arithmetic mean of 19.2 worms per child. A concurrent
      socioeconomic household survey was conducted by visitation and interview.
      Exposure to infection was assessed by environmental, demographic, behavioral, and
      socioeconomic indicators. Ascaris lumbricoides aggregations were associated with
      gender, housing style, ethnicity, and agricultural factors. The results suggest
      that exposure and infection are ubiquitous in this child population, and that A.
      lumbricoides intensity is influenced by gender-related behavioral and
      environmental factors that contribute to exposure.

PMID- 9645844
TI  - Comparison of three estimators of species richness in parasite component
      communities.
AB  - Comparisons of species richness between parasite component communities are often
      confounded by uneven sampling effort and the possibility that rare species have
      been missed from some component communities. The use of nonparametric estimators
      of species richness could potentially alleviate this problem by allowing the
      number of missing species to be extrapolated from the observed data. The
      performance of 3 estimators and their sensitivity to true species richness and
      the frequency of rare species, i.e., species with low prevalence, were tested
      using computer-simulated parasite communities. When the number of hosts examined
      in a sample is large, the observed species richness is an accurate estimate of
      true richness; no extrapolation is necessary even when rare species make up a
      large part of the community. At small sample sizes, observed species richness is
      a poor underestimate of true richness. The jackknife estimator and Chao's
      estimator both improve the estimate of species richness, but they are imprecise
      and can seriously overshoot the true richness value when the community includes
      many rare species. The bootstrap estimator. on the other hand, gives a better
      estimate than observed richness. Bootstrap estimates are also less variable and
      less likely to overestimate true richness, independently of how frequent rare
      species are in the community. This estimator provides a better, but conservative,
      estimate of true richness than observed richness and should be used to correct
      for inadequate host sampling. Data from natural communities suggest that the use
      of richness estimators is often justified, and that many parasite species may
      regularly escape detection.

PMID- 9645845
TI  - Host-mediated site segregation of ectoparasites: an individual-based simulation
      study.
AB  - Site segregation of coexisting ectoparasite species may result either from a
      direct interaction such as resource competition between them or from a host
      mediated interaction. Here we present an individual-based model for the
      coevolution of 1 host and 2 parasite species to study this latter hypothesis.
      Parasite species are generalists at the start of the simulation and develop site
      specificities under the following assumptions. Parasite populations are not
      subject to resource limitations but are limited directly by host defense as
      predation. Hosts have 2 sites that need different defensive abilities to reduce
      their parasite burden. Parasites need to exhibit different evasive abilities to
      survive on different sites. Host grooming selects parasites for an increasing
      capability for evasion, whereas parasites select hosts for an increasing
      efficiency of grooming. Two trade-offs are incorporated into the model: one
      between host defensive abilities on the 2 sites, and another between parasite
      evasive abilities on the 2 sites. We conclude that, under these assumptions, the
      optimization of host defense and parasite evasion strategies may select
      ectoparasites for site segregation and this may stabilize the coexistence of
      parasite species.

PMID- 9645846
TI  - Lyme disease spirochetes in ticks from northeastern China.
AB  - During May 1996, field surveys on Lyme disease spirochetes were conducted in
      Beijing, Shenyang, Fushun, and Inner Mongolia in northeastern China. The ticks
      collected consisted of 3 genera and 12 species. Of these, Ixodes persulcatus was
      dominant in sun-exposed vegetation in forests in Inner Mongolia; 57 Borrelia
      strains (55/123 unfed adults and 2/5 immature stages fed on a rodent) were
      obtained from this tick by BSK culture. Additionally, 2/2 Apodemus peninsulae
      were positive. Ixodes nipponensis, Ixodes pavlovskyi, Haemaphysalis douglasi, and
      Haemaphysalis megaspinosa, newly recorded in China, and other Haemaphysalis spp.
      were all negative for Borrelia. Based on a polymerase chain reaction restriction
      fragment length polymorphism analysis of the 45 strains successfully subcultured,
      these were classified as 29 Borrelia garinii and 16 Borrelia afelii. These
      strains seemed to be more closely related to Japanese strains in genetic features
      than to those from Europe. The result of sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis suggested more diversity in both genospecies, but Borrelia
      burgdorferi sensu stricto was not found.

PMID- 9645847
TI  - Ultrastructure of the oocysts, sporocysts, and sporozoites of Toxoplasma gondii.
AB  - Transmission and scanning electron microscopy were used to study the
      ultrastructure of the oocysts, sporocysts, and sporozoites of the VEG strain of
      Toxoplasma gondii and to compare the ultrastructure of sporozoites with
      tachyzoites (from the peritoneum of mice) and bradyzoites (from brain tissue
      cysts in mice). Oocysts were surrounded by a thin veil of finely reticulate
      material. The oocyst wall consisted of 3 layers and contained a previously
      unknown disc-shaped micropyle that appeared as a depression in the oocyst wall.
      The sporocyst contained 4 sporozoites and a residuum of lipid and amylopectin
      granules. The sporocyst wall was 3-layered with the innermost layer consisting of
      4 curved plates held together at sutures by an interposed strip. Exposure to
      excysting fluid caused the interposed strip to separate from the curved plates,
      which curled inward releasing the sporozoites. Sporozoites had a posteriorly
      located nucleus and all the organelles typical for coccidian zoites. Sporozoites,
      tachyzoites, and bradyzoites had similar numbers of rhoptries but differed in the
      numbers and sizes of micronemes, dense granules, amylopectin granules, and lipid
      bodies.

PMID- 9645848
TI  - Demonstration of Taenia crassiceps cysteine proteinase activity in tegumentary
      lysosome-like vesicles.
AB  - Larval stages of Taenia species survive for prolonged periods in the tissues of
      their intermediate hosts. Other groups have demonstrated that host
      immunoglobulins are taken up by the cysticerci by adsorptive endocytosis,
      degraded, and the amino acids incorporated into parasite proteins. We have shown
      that a 43-kDa cysteine proteinase is the major parasite enzyme that degrades
      immunoglobulin in vitro. To localize this enzyme in situ, Taenia crassiceps
      cysticerci were incubated with the peptide substrate Z-Phe-Arg
      methoxynaphthylamide. Free methoxynaphthylamide was coupled to p-rosanilin and
      osmium and visualized by transmission electron microscopy. Initial studies of
      cysticerci incubated without substrate confirmed the normal microanatomy and
      absence of significant host inflammation. In comparison to controls with no
      substrate, sections of cysticerci incubated with substrate revealed electron
      dense deposits in round vesicles. The vesicles were found primarily within the
      tegumentary cytons and internuncial processes, a location similar to that
      described for vesicles associated with adsorptive endocytosis. There were
      proportionately more endocytotic vesicles and electron-dense vesicles in smaller
      cysticerci than larger ones. Formation of electron-dense deposits was inhibited
      by heat and partially inhibited by the cysteine proteinase inhibitor E-64. These
      data are consistent with localization of the cysteine proteinase activity to
      lysosome-like vesicles.

PMID- 9645849
TI  - Taenia crassiceps cysticercosis: humoral immune response and protection elicited
      by DNA immunization.
AB  - The purpose of this study was to evaluate DNA vaccination in cysticercosis
      prevention by using a Taenia crassiceps cDNA of a recombinant antigen (KETc7)
      that has been reported as protective against murine cysticercosis. The KETc7 cDNA
      was cloned into the pcDNA3 plasmid alone or with the betaglycan signal peptide
      sequence (pTc-7 and pTc-sp7, respectively). Positive expression of the pTc-sp7
      product was confirmed by transfection of C33 cells and immunofluorescence using
      sera of mice infected with T. crassiceps. Immunization of mice with 3 injections
      of pTc-sp7 DNA at the higher dose (200 microg) was the most effective to induce
      antibody with or without bupivacaine. Immunization with pTc-sp7 induced
      protection against challenge with T. crassiceps cysticerci as successfully as
      previously observed with the KETc7 recombinant protein. Antibodies elicited by
      DNA immunization with pTc-sp7 specifically reacted with the native protein of 56
      kDa previously reported, which is immunolocalized in the tegument of T.
      crassiceps cysticerci. The 56-kDa antigen is also present in Taenia solium
      oncospheres, cysticerci, and adult tissue. The protection induced in DNA
      immunized mice and the observation that the injected plasmid remains as an
      episomic form within muscle cells, encouraged us to continue testing this
      procedure to prevent T. solium cysticercosis.

PMID- 9645851
TI  - The specificity of behavioral fever in the cricket Acheta domesticus.
AB  - When infected, some insects can raise their body temperature by moving to warmer
      areas. This behavioral fever response can help the host overcome infection.
      However, not all parasites and pathogens are equally susceptible to increases in
      host temperature. Elevating the temperature of the cricket Acheta domesticus from
      room temperature (22 C) to 33 C did not reduce the survival of parasitoid flies
      or reduce the number of gregarine gut protozoans, and crickets infested with
      these parasites showed no increase in their temperature preference. Warmer
      temperatures (33 C) did not increase the survival of crickets infected with the
      bacterium Serratia marcescens, and infected crickets did not prefer warmer
      temperatures. However crickets infected with the intracellular parasite
      Rickettsiella grylli were more likely to survive when the host was exposed to
      warmer temperatures. Crickets infected with R. grylli increased their preferred
      temperature from 26 C to 32 C. In A. domesticus, behavioral fever may be a
      specific response induced by relatively few pathogens and parasites. Behavioral
      fever in insects may differ in this respect from fever in mammals that can be
      elicited by a wide variety of parasites and pathogens.

PMID- 9645850
TI  - Demonstration of shared carbohydrate epitopes in intestinal proteins of some
      bovine gastrointestinal nematodes.
AB  - The presence of shared carbohydrate intestinal epitopes in bovine
      gastrointestinal nematodes was demonstrated. Proteins were extracted from the
      intestinal tissue of a laboratory strain of adult Haemonchus placei and used to
      produce monoclonal antibodies (mAb). Analysis of this detergent extract by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis revealed 7-9 bands ranging
      from approximately 39 to 298 kDa. The mAbs reacted with periodate-sensitive
      epitopes and, in western blots, recognized high molecular weight protein bands
      (approximately 111-298 kDa). Immunohistochemical studies with the mAbs verified
      the intestinal location of the epitope(s) in the laboratory strain as well as in
      a recent field isolate of H. placei. Epitope(s) were conserved among species
      examined within the Trichostrongyloidea (Ostertagia ostertagi, Cooperia punctata,
      Haemonchus placei, and Haemonchus contortus), semiconserved among species within
      the Strongyloidea (present in Oesophagostomum radiatum, absent in Oesophagostomum
      venulosum), and absent in the only species examined in the Ancylostomatoidea
      (Bunostomum phlebotomum).

PMID- 9645852
TI  - Structure of Leptorhynchoides thecatus and Pomphorhynchus bulbocolli
      (Acanthocephala) eggs in habitat partitioning and transmission.
AB  - The role of egg structure in transmission and habitat use of Leptorhynchoides
      thecatus and Pomphorhynchus bulbocolli (Acanthocephala) was investigated. During
      storage in tap water at 4 C, the outer membrane of L. thecatus eggs was lost,
      releasing ribbonlike filaments of the fibrillar coat. After similar storage, the
      outer membrane and fibrillar coat of P. bulbocolli eggs remained intact. Eggs of
      L. thecatus entangled in algae, whereas those of P. bulbocolli settled to the
      substratum. Leptorhynchoides thecatus infections in amphipod intermediate hosts
      were significantly more prevalent and dense when eggs were allowed to entangle
      than when they were not. Prevalence and relative density of P. bulbocolli
      infections in amphipods were not significantly different between trials in which
      entanglement was possible and those in which it was not. These results indicate
      that although the same species of amphipod, Hyalella azteca, is the intermediate
      host for both acanthocephalan species, mechanisms of transmission differ.
      Differences in fibrillar coats result in segregation of the environment in a
      manner that affects transmission and occurrence in intermediate hosts.

PMID- 9645853
TI  - First record of trypanosomes in Tasmanian bandicoots.
AB  - Trypanosomes were observed in 38% of blood smears from southern brown bandicoots
      (Isoodon obesulus) and in 10% of blood smears from eastern barred bandicoots
      (Perameles gunnii). This is the first record of such hemoparasites in Tasmanian
      marsupials. There appeared to be a statistically significant size difference
      between trypanosomes found in the 2 bandicoot species, suggesting the possibility
      of 2 distinct species of parasite. There appears to be a distinction between the
      trypanosomes found in our temperate Isoodon species and the tropical bandicoot.
      Isoodon macrurus. The use of the microhematocrit method provided an effective
      means for concentrating trypanosomes, whereas image analysis was a more effective
      method than the ocular micrometer for obtaining accurate measurements.

PMID- 9645854
TI  - Vector ability of mosquitoes for isolates of Plasmodium elongatum from raptors in
      Florida.
AB  - Three isolates of Plasmodium elongatum were obtained from 3 species of raptors
      (red-tailed hawk [Buteo jamaicensis], bald eagle [Haliaeetus leucocephalus], and
      eastern screech owl [Otus asio]) from Florida using isodiagnostic techniques in
      Pekin ducks (Anas platyrhynchos). Six to 10 species of mosquitoes were tested for
      susceptibility to these 3 isolates. Complete development of the sporogonic cycle
      of the 3 isolates of P. elongatum occurred in 3 species of mosquitoes, Culex
      nigripalpus, Culex restuans, and Culex salinarius. The pattern of susceptibility
      was similar among the 3 isolates of P. elongatum in Cx. nigripalpus. Culex
      restuans and Cx. salinarius were significantly more susceptible than Cx.
      nigripalpus to the 3 isolates of P. elongatum tested. Culex nigripalpus
      transmitted all 3 isolates of P. elongatum from duck to duck both by bite and
      after intraperitoneal injection of sporozoites. Infections of the 2 isolates
      tested occurred in ducks after intraperitoneal injection of sporozoites from Cx.
      restuans and Cx. salinarius. The results suggest that these 3 Culex species are
      potential vectors of P. elongatum from raptors in Florida.

PMID- 9645855
TI  - Studies on infections with two strains of Plasmodium inui from Taiwan in rhesus
      monkeys and different anopheline mosquitoes.
AB  - Rhesus monkeys infected with the Taiwan strains of Plasmodium inui could be
      appropriate models for understanding host-parasite relationships during long-term
      chronic infection. Two strains of P. inui originally from Taiwan were studied in
      rhesus monkeys and different anopheline mosquitoes. Maximum parasite counts for
      13 intact animals infected with the Taiwan I strain ranged from 22,215 to
      760,000/microl (median maximum parasite count = 242,800/microl). Following
      splenectomy, the maximum parasite count for the 9 animals ranged from 160,000 to
      2,360,000/microl (median = 1,160,000/microl). Sporozoite transmission was
      demonstrated via the bites of infected Anopheles dirus mosquitoes and by the
      intravenous inoculation of sporozoites harvested from the guts of infected
      Anopheles maculatus. Prepatent periods were 12 and 20 days, respectively. With
      monkeys infected with the Taiwan II strain, the parasite counts when intact were
      from 40,882 to 223,686/microl. After splenectomy, maximum parasite counts ranged
      from 96,750 to 1,960,000/microl (median maximum parasite count for 8
      splenectomized animals = 840,000/microl). Two transmissions were obtained via the
      bites of infected An. dirus mosquitoes; prepatent periods were 10 days. Limited
      studies with progressively increasing doses of pyrimethamine resulted in
      parasites more resistant to treatment.

PMID- 9645856
TI  - Respiratory burst assay of head kidney macrophages of ayu, Plecoglossus
      altivelis, stimulated with Glugea plecoglossi (Protozoa: Microspora) spores.
AB  - The respiratory burst assay was conducted using the nitroblue tetrazolium
      reduction method and horseradish peroxidase method to investigate the events when
      ayu head kidney macrophages phagocytize fresh and formalin-killed Glugea
      plecoglossi spores. The production of O2 against G. plecoglossi spores was
      negligible compared to zymosan (P < 0.01). Zymosan-induced O2 production was
      markedly inhibited by adding G. plecoglossi spores simultaneously (P < 0.01).
      This phenomenon was dose dependent, and killed spores were less inhibitory than
      fresh spores. The production of H2O2 was drastically increased when G.
      plecoglossi spores were added (P < 0.01), and most spores were phagocytized. From
      these results, it is suggested that G. plecoglossi spores modulate the host's
      phagocytic response to establish infection.

PMID- 9645857
TI  - Filariasis and erisipela in Santo Domingo.
AB  - This study examined acute-convalescent changes in diagnostic anti-streptococcal
      antibodies by the anti-streptolysin O (ASO) and anti-DNAase B (ADAB) tests among
      patients (n 28) with lymphedema and recurrent erisipela of the lower limb,
      comparing them with endemic normal control residents (n=25). The study was based
      in Villa Francisca, an urban focus of Bancroftian filariasis in eastern Santo
      Domingo, capital of the Dominican Republic. The acute signs and symptoms of
      erisipela were consistent with a diagnosis of bacterial cellulitis. The ASO test
      was especially successful at demonstrating a rise in mean titer during
      convalescence, whereas the ADAB produced about the same frequency of significant
      increases (0.2 log titer) as did the ASO. When subjects were scored as responders
      if mounting a minimal titer increase by either test, patients were found more
      frequently positive than were controls (chi2=5.3, P=0.02). About half (54%) of
      all patients mounted at least a minimal antibody increase. Filaria-specific IgG4
      antibodies were absent from all sera of 20 residents of a nonendemic Dominican
      mountain town but appeared in about two-thirds of the sampled residents of the
      endemic barrio. Notably however, levels did not change between the acute phase
      and convalescence. These findings are consistent with the hypothesis that
      recurrent streptococcal invasion of the lymphatics may be a significant factor
      triggering or amplifying lymphedema and elephantiasis in patients with chronic
      filariasis.

PMID- 9645858
TI  - Three new Sarcocystis species, Sarcocystis giraffae, S. klaseriensis, and S.
      camelopardalis (Protozoa: Sarcocystidae) from the giraffe (Giraffa
      camelopardalis) in South Africa.
AB  - Three new Sarcocystis species recovered from muscle fibers of the skeletal
      musculature of a giraffe in South Africa are described based on light and
      electron microscopy. Sarcocystis giraffae n. sp. formed slim macrocysts with a
      parasite-induced connective tissue encapsulation of the host muscle fiber in
      which the plasma membrane of the latter remained unaltered. The sarcocyst wall
      represented a new ultrastructural type that is characterized by fingerlike villar
      protrusions with a hairlike projection at the tip, containing microtubules
      penetrating the ground substance. Sarcocystis klaseriensis n. sp. formed small
      filiform microcysts with kinked finger-shaped villar protrusions of the wall,
      containing scattered microtubules or filaments, and represented another new
      ultrastructural type. Sarcocystis camelopardalis n. sp. formed small filiform
      microcysts with straplike villar protrusions of the wall, containing chainlike
      osmiophilic structures, and represented again a new ultrastructural type.

PMID- 9645859
TI  - Subulura saloumensis n. sp. (Nematoda, Subuluroidea) from four species of rodents
      in Senegal.
AB  - A new species of the genus Subulura is described from 4 new rodent hosts:
      Arvicanthis niloticus, Mastomys erythroleucus, Mastomys huberti, and Tatera
      gambiana. Subulura saloumensis n. sp. differs from the congeneric species by the
      morphology of its head. the absence of buccal lobes, the length of right and left
      spicules, the absence of caudal alae, and the existence of a caudal papillae with
      a sensorial bristle. The latter, which we observe for the first time in specimens
      gathered from M. huberti, has never previously been described in a species of the
      genus Subulura.

PMID- 9645860
TI  - Echinocephalus janzeni n. sp. (Nematoda: Gnathostomatidae) in Himantura pacifica
      (Chondrichthyes: Myliobatiformes) from the Pacific coast of Costa Rica and
      Mexico, with historical biogeographic analysis of the genus.
AB  - Echinocephalus janzeni n. sp. in the stingray, Himantura pacifica, is described
      from the eastern Pacific Ocean off the coasts of Costa Rica and southern Mexico.
      On the basis of the presence of 6 postanal caudal papillae, and modified annules
      anterior to the caudal alae in males, E. janzeni is most similar to
      Echinocephalus daileyi and Echinocephalus diazi. Specimens of E. janzeni are
      distinguished from those of E. daileyi by bilobed caudal alae and long cervical
      sacs that extend up to 65% of the length of the esophagus; E. janzeni is
      differentiated from E. diazi by the number of rows of cephalic spines (30-38 vs.
      26-27), arrangement of the postanal caudal papillae, 3 rather than 2 preanal
      papillae, relative position and distance between the anus and vulva (395-460
      microm vs. 70 microm), the digitiform female tail with a terminal cuticular fold,
      and the length of the female tail (450-480 microm vs. 270 microm). Cladistic
      analysis of the 10 Echinocephalus spp. resulted in a single most parsimonious
      tree (consistency index=0.893) and placed E. janzeni in a highly derived subclade
      where E. daileyi is the sister species of E. diazi + E. janzeni. Historical
      biogeographic analysis of hosts and parasites provides support for origins in the
      Pacific rather than the Atlantic for the potamotrygonid stingrays.

PMID- 9645861
TI  - Reevaluation of Physaloptera bispiculata (Nematoda: Spiruroidaea) by light and
      scanning electron microscopy.
AB  - This study was undertaken to clarify several aspects of morphological and
      taxonomic characters of Physaloptera bispiculata Vaz and Pereira, 1935, a
      parasite of the water rat, Nectomys squamipes. The cephalic structures (including
      lips, papillae, teeth, amphids, and porous areas) and details of the posterior
      end of male and female adult worms were examined by scanning electron microscopy,
      leading to the addition of new taxonomic characters for this species. We consider
      P. bispiculata a valid species, based on a comparative analysis of the specific
      characters for P. bispiculata and P. getula Seurat, 1917, including the
      morphology and morphometry of body structures as well as number and disposition
      of caudal papillae of the males.

PMID- 9645862
TI  - Two new Huffmanela species, H. japonica n. sp. and H. shikokuensis n. sp.
      (Nematoda: Trichosomoididae), from marine fishes in Japan.
AB  - Two new species of trichuroid nematodes. Huffmanela japonica n. sp. and
      Huffmanela shikokuensis n. sp., are established on the basis of their egg
      morphology and biological characters; the eggs of both species occur in the
      musculature of marine fishes from the Inland Sea of Japan. The dark-shelled eggs
      of H. japonica are found locally in masses ("black spots") in the flesh of
      Upeneus bensasi (Temminck et Schlegel) (Mullidae, Perciformes) and are
      characterized mainly by their shape and size (58-69 x 26-30 microm), an aspinose
      superficial transparent envelope enclosing the egg proper, relatively small polar
      plugs, and by their thick egg wall (4-5 microm). The eggs of H. shikokuensis are
      also dark-colored and are found evenly distributed in the musculature of
      Stephanolepis cirrhifer (Temminck et Schlegel) (Monacanthidae,
      Tetraodontiformes); they are characterized mainly by their shape and size (78-90
      X 36-45 microm), by a very thin and aspinose superficial transparent envelope,
      large polar plugs, and relatively thin egg wall (3 microm). Histological sections
      of the host's infected musculature showed the presence of H. shikokuensis
      nematodes inside the muscle cells and in the intercellular spaces. A key to
      Huffmanela species based on egg morphology is provided.

PMID- 9645863
TI  - Redescription of Hapalotrema mistroides (Monticelli, 1896) and Hapalotrema
      synorchis Luhman, 1935 (Digenea: Spirorchidae), with comments on other species in
      the genus.
AB  - Hapalotrema mistroides (Monticelli, 1896) Stiles and Hassall, 1908 and
      Hapalotrema synorchis Luhman, 1935 are redescribed using specimens from the
      loggerhead turtle. Caretta caretta (L.). The redescription of H. mistroides is
      based on specimens collected by Looss and described as Hapalotrema constrictum
      Leared, 1862 and renamed Hapalotrema loossi Price, 1934, which is now considered
      a junior synonym of H. mistroides. Hapalotrema orientalis Takeuti, 1942 is
      considered a junior synonym of Hapalotrema synorchis. The redescriptions are
      consistent with the originals but provide an unreported range of variation while
      adding new information about the reproductive systems. Reexamination of
      Hapalotrema dorsopora Dailey, Fast, and Balazs, 1993 confirms the presence of a
      reproductive system typical for the genus and the absence of a dorsal genital
      pore; therefore, H. dorsopora is reduced to a junior synonym of Hapalotrema
      mehrai Rao, 1976. Four valid species of Hapalotrema are recognized: H.
      mistroides. H. synorchis, H. postorchis, and H. mehrai, and a key to the species
      is provided.

PMID- 9645864
TI  - Characterization of trypanosomes from the subgenus Schizotrypanum isolated from
      bats, Eptesicus sp. (Chiroptera: Vespertilionidae), captured in Florianopolis,
      Santa Catarina State, Brazil.
AB  - Seven Trypanosoma spp. isolates obtained from bats (Eptesicus sp.) were
      characterized using experimental infection in mice, triatomines, and culicines;
      complement lysis; indirect fluorescence assays; as well as isoenzyme and random
      amplified polymorphic DNA (RAPD) profiles. The Trypanosoma sp. isolates were
      compared with Trypanosoma cruzi, Trypanosoma rangeli. and 2 other bat
      trypanosomes species, Trypanosoma vespertilionis and Trypanosoma hastatus.
      Trypanosoma sp. isolates were different from the other species in all
      experiments, except in complement lysis. Experimental infection of triatomines
      and culicines with Trypanosoma sp. proved to be transitory. These parasites were
      noninfective for both normal and immunosuppressed mice. Isoenzyme and RAPD
      profiles obtained for Trypanosoma sp. were quite distinct from T. cruzi and T.
      rangeli and closely related to T. vespertilionis and T. hastatus. No cross
      reaction was observed between sera from mice infected with Trypanosoma sp. and
      the other trypanosomatids and vice-versa. Trypanosoma sp. induced no protection
      against T. cruzi infection in mice. The very low, or nonsimilarity between
      Trypanosoma sp. isolates and the other species used in this study suggests that
      they might be members of a distinct bat trypanosome species. However, further
      studies should be done to prove their affinities with Trypanosoma cruzi
      marinkellei, another trypanosome species from bats.

PMID- 9645865
TI  - Trypanosoma cruzi tubulin eliminated in the urine of the infected host.
AB  - In previous studies we have identified and characterized an 80-kDa Trypanosoma
      cruzi urinary antigen (UAg) eliminated during acute infection. Polyclonal
      antibodies raised against this antigen revealed by western blotting and
      immunoprecipitation analyses showed the existence of another antigenic component
      of 50-55 kDa in the UAg preparation. The antiserum was also used for screening of
      a T. cruzi expression library. Sequencing of inserts from selected cDNA clones
      showed high homology with the 3' end of the T.cruzi beta-tubulin gene sequence
      encoding for the C-terminus of the protein. The presence of T. cruzi tubulin in
      the UAg was confirmed by immunoprecipitation of a 50-55-kDa protein from 125I
      labeled UAg with monoclonal antibodies (MAbs) to human alpha/beta-tubulin.
      Interestingly, MAbs recognized radiolabeled T. cruzi tubulin eliminated in the
      urine of infected mice 24 hr postinoculation of [35S]methionine-labeled viable
      trypomastigotes. Tubulin found in the urine proved to be of T. cruzi origin
      because this protein could not be identified in urinary specimens from uninfected
      animals or mice acutely infected with Leishmania infantum or Toxoplasma gondii.
      We conclude that tubulin is one of the parasite antigens eliminated in the urine
      of T. cruzi-infected hosts. This finding may be used to develop a noninvasive
      procedure for early diagnosis of Chagas' disease.

PMID- 9645866
TI  - New data on the early development of Hysterothylacium aduncum (Nematoda,
      Anisakidae).
AB  - This note reports on incidental observations of the early development of the
      third-stage larvae of Hysterothylacium aduncum from gadid fishes. Gravid H.
      aduncum females were collected from Pollachius virens, Pollachius pollachius.
      Gadus morhua, and Molva molva in Norwegian waters. The eggs were incubated at 20
      per thousand salinity and 5 C. Spontaneous hatching of third-stage larvae was
      observed 10-25 days after egg deposition. These larvae were long lived and could
      infect Acartia tonsa copepods, the infections being maintained for up to 34 days.
      The morphology of the third-stage larvae in the copepods and some traits of the
      life cycle were similar to those reported in previous studies. However, our
      results disagree with evidence suggesting that H. aduncum eggs rarely hatch, and
      hatched larvae have lower survival and a poorer ability to infect the first
      intermediate host than unhatched ones. It is difficult to account for these
      discrepancies because information on the early development of Hysterothylacium
      species is incomplete. However, we tentatively suggest that differences in the
      early development of H. aduncum may indicate the existence of at least 2
      different taxonomic entities in the North Atlantic, which is consistent with
      previous evidence based on morphological traits.

PMID- 9645867
TI  - Helminths of the Canadian toad, Bufo hemiophrys (Amphibia: Anura), from Alberta,
      Canada.
AB  - Forty adult Bufo hemiophrys from Alberta, Canada, were examined for helminths.
      Four species were found: a trematode, Gorgoderina simplex, and 3 nematodes,
      Cosmocercoides variabilis, Oswaldocruzia pipiens, and Rhabdias americanus.
      Rhabdias americanus had the highest prevalence of helminths (73%); C. variabilis
      had the highest mean intensity (26+/-33 SD). Bufo hemiophrys represents a new
      host record for each species of helminth.

PMID- 9645868
TI  - Adaptation of a strain of Plasmodium vivax from Mauritania to New World monkeys
      and anopheline mosquitoes.
AB  - A strain of Plasmodium vivax from Mauritania was adapted to develop in Aotus
      lemurinus griseimembra, Aotus nancymai, Saimiri boliviensis, and hybrid Aotus
      monkeys. Infections were induced via the inoculation of sporozoites dissected
      from the salivary glands of Anopheles gambiae, Anopheles freeborni, and Anopheles
      stephensi mosquitoes or the intravenous passage of infected erythrocytes.
      Infections in 3 A. lemurinus griseimembra monkeys readily infected mosquitoes.
      Four lines of the Mauritania parasites have been stored frozen for further
      reference.

PMID- 9645869
TI  - Serologic prevalence of Toxoplasma gondii in chickens in Madras, India.
AB  - Serum samples from 185 chickens (Gallus gallus) collected from the various
      slaughter markets in and around Madras City, India were examined for antibodies
      to Toxoplasma gondii using the modified agglutination test incorporating
      mercaptoethanol. Antibodies (> or = 1:25) to T. gondii were found in 39.5% of
      sera. Antibody titers of individual sera (% in parentheses) were 1:25 (8.1%),
      1:50 (10.8%), 1:100 (6.5%), 1:200(2.7%), 1:400 (4.3%), 1:800 (5.9%) 1:1,600
      (0.5%), and 1:3,200 (0.5%).

PMID- 9645871
TI  - Comparative observations on cercariae and metacercariae of Echinostoma trivolvis
      and Echinoparyphium sp.
AB  - Comparative observations were made on cercariae of Echinoparyphium sp. from Physa
      gyrina in Charlie's pond, Stokes County, North Carolina and cercariae of
      Echinostoma trivolvis from Helisoma trivolvis in Northampton County,
      Pennsylvania. The cercaria of Echinoparyphium sp. has 43 collar spines, lacks
      penetration and paraesophageal glands, and has a conical tail without fin folds.
      The cercaria of E. trivolvis has 37 collar spines, penetration and paraesophageal
      glands, a finger-like process at the tip of the tail and fin folds. The length of
      the cercarial body and tail of E. trivolvis was significantly greater than that
      of Echinoparyphium sp. Cercariae of both species encysted in Biomphalaria
      glabrata snails in single and concurrent infections. In concurrent infections
      with a single cercaria of each species, 2 encysted metacercariae were adjacent to
      each other in the saccular kidney of the snail at 24 hr postinfection. The
      diameter of encysted metacercariae of E. trivolvis was significantly greater than
      that of Echinoparyphium sp. Echinoparyphium sp. metacercariae excysted at 39 C in
      an alkaline trypsin-bile salts medium used previously to excyst E. trivolvis. The
      length of excysted metacercariae of E. trivolvis was significantly greater than
      that of Echinoparyphium sp.

PMID- 9645870
TI  - Cryptosporidiosis in a bat (Eptesicus fuscus).
AB  - Cryptosporidial infection was diagnosed histologically in the small intestine of
      a big brown bat (Eptesicus fuscus) from Oregon. This is the first report of
      cryptosporidiosis in a bat.

PMID- 9645872
TI  - Intestinal parasite infections after extended use of chloroquine or primaquine
      for malaria prevention.
AB  - Comparative results of baseline and endpoint screening for intestinal parasites
      are reported from Javanese men enrolled in a year-long, placebo-controlled
      malaria prophylaxis trial in Irian Jaya. The objective was to detect nontarget
      qualitative changes that may have resulted from prolonged chloroquine (300 mg
      base weekly) or primaquine (0.5 mg base/kg daily) prophylaxis. Fresh fecal
      specimens were examined (blinded trial) for parasites and ova using a modified
      Kato-Katz thick smear method. More than 88% (94/106) of the baseline population
      was infected by 1 or more parasite species of which hookworm and Blastocystis
      hominis were dominant. Paired comparison between baseline and endpoint revealed
      no significant changes within the primaquine or chloroquine groups with regard to
      the variety of species found, the mean number of species or ova/subject, the
      relative proportion of infections caused by these species, or the occurrence of
      parasite-free, single, and multiple infections. Relative to placebo, there was a
      significantly greater proportion of infections by Entamoeba histolytica/dispar
      and a lower mean hookworm egg count in the chloroquine group. The endpoint
      proportion of new or increased infections in the primaquine group was
      significantly lower than that of the chloroquine group but comparable to that of
      the placebo. Despite the dosage employed, the frequency and duration of use, and
      excretion primarily through the bowels as the active parent compound, primaquine
      appeared to have little or no significant effect against a variety of common
      intestinal parasites. These largely negative results lend support for the safety
      and acceptability of primaquine as a daily malaria prophylactic in a population
      frequently at risk of intestinal helminth infections.

PMID- 9645873
TI  - First records of Amblyomma americanum, Ixodes (Ixodes) dentatus, and Ixodes
      (Ceratixodes) uriae (Acari: Ixodidae) from Maine.
AB  - The first records of 3 ixodid tick species collected in the state of Maine are
      reported. A total of 23 records of the lone star tick, Amblyomma americanum (L.,
      1758), in 11 counties from hosts with no history of travel outside the state
      demonstrates that this tick is now a resident of Maine. Ixodes dentatus Marx,
      1899 is recorded from Waldo and Lincoln counties, and Ixodes uriae White, 1852 is
      recorded from Matinicus Rock in Knox County. This is the first report of I. uriae
      from the eastern United States. Disease agents such as those causing human
      monocytic ehrlichiosis, Lyme disease, Rocky Mountain spotted fever, and several
      arboviruses have been recorded from 1 or more of these tick species.

PMID- 9645874
TI  - Effects of macrocyclic lactones on ingestion in susceptible and resistant
      Haemonchus contortus larvae.
AB  - The effects of ivermectin and ivermectin aglycone on pharyngeal uptake of a
      carbohydrate substrate (3H-inulin) were measured in larvae of a macrocyclic
      lactone (ML)-susceptible isolate and 2 ML-resistant isolates of Haemonchus
      contortus. The resistant isolates showed a tolerance (in terms of the
      concentration of compound required to reduce feeding to 50%) toward ivermectin of
      approximately 4.5- and 9-fold and toward ivermectin aglycone of approximately 14
      fold, compared to the susceptible isolate. This indicates that susceptible and
      resistant isolates can be readily distinguished on the basis of the sensitivity
      of pharyngeal uptake to MLs. The use of various metabolic inhibitors in this
      assay system did not reveal the nature of the resistance mechanism. Pretreatment
      of resistant larvae with inhibitors of multidrug resistance mechanisms (P
      glycoprotein and multidrug resistance protein) and detoxification enzymes
      (monooxygenases, esterases, and glutathione transferases) did not reduce their
      level of tolerance to the ivermectin aglycone.

PMID- 9645875
TI  - Complete development of the porcine coccidium Isospora suis Biester, 1934 in cell
      cultures.
AB  - Development from inoculated sporozoites to unsporulated oocysts of Isospora suis
      Biester, 1934 is described in a swine testicular (ST) cell line. Sporozoites
      penetrated ST cells within 1 hr postinoculation (PI). Development was initially
      by endodyogeny to produce binucleate type I meronts and type I merozoites.
      Division by endodyogeny continued during the 13-day observation period and type I
      merozoites were the developmental stages most abundant at observation periods >3
      days PI. Mutinucleate type II meronts and type II merozoites were first observed
      7 days PI. Gamonts and oocysts were present 12 days PI. Oocysts did not sporulate
      in vitro. The ultrastructural features of stages were similar to those that occur
      in the pig host.

PMID- 9645876
TI  - Axenic cultivation of Trichomonas vaginalis in a serum-free medium.
AB  - Mammalian serum or bovine serum albumin are essential for Trichomonas vaginalis
      cultivated under axenic conditions. Unfortunately, these components inhibit
      several biological properties of these parasites. PACSR is a serum replacement,
      free of bovine serum albumin. used for axenic cultivation of Entamoeba
      histolytica. We show that PACSR is also useful for axenic cultivation of T.
      vaginalis. Tubes containing 5.5 ml PEHP, or TYI basal media, plus 8% PACSR (v/v),
      were inoculated with 10(3) trichomonads/ml from 3 strains (GT-3, GT-13, and GT
      15) and incubated at 36.5 C for 72 hr. Depending on the strain, cultures grown in
      PEHP plus PACSR reached densities of 50% (GT-13), 63% (GT-3), or 82% (GT-15) as
      compared to controls grown in PEHPS. On the other hand, yields of GT-3, GT-13,
      and GT-15 maintained in TYI plus PACSR were, respectively, 53%, 57%, and 67%
      among those of cultures grown in TYI-S-33. In all experiments, PEHPS and TYI-S-33
      contained 8% bovine serum. Yields reached in PEHPS were 2.07+/-0.275 to 4.83+/
      4.41 x 10(6) trichomonads/ml, whereas in TYI-S-33, densities were 1.68+/-0.315 to
      4.16+/-8.07 x 10(6) trichomonads/ml. In conclusion, PACSR added to PEHP or TYI
      media is useful for axenic cultivation of T. vaginalis in the absence of serum or
      bovine serum albumin. PACSR could be useful in performing analyses of biological
      properties that are inhibited by serum or any of its components.

PMID- 9645877
TI  - Genotypic analysis of Toxoplasma gondii isolates from pigs.
AB  - To determine the prevalence of the 3 primary clonal lineages of Toxoplasma gondii
      (strain types I, II, and III) in a potential food source of infection for humans,
      we analyzed 43 isolates of T. gondii that had been collected from pigs at an
      abattoir in Iowa. Parasites were harvested as in vitro-grown tachyzoites, and
      their genotypes were determined at the SAG1 and SAG2 loci. On the basis of the
      allele identified at the SAG2 locus, isolates were grouped into 1 of the 3
      primary lineages. Type II strains were by far the most prevalent, accounting for
      83.7% of the isolates. The type III genotype was identified in only 16.3% of the
      isolates. These prevalences differ significantly from a previous sampling of
      isolates from animals but are similar to the frequencies with which they occur in
      human disease cases. Similar to the previously characterized strain P89, strains
      P62 and P105 appeared to have recombinant genotypes. The type I genotype was not
      identified in the isolates from pigs although these strains have previously been
      shown to account for approximately 10-25% of toxoplasmosis cases in humans.

PMID- 9645878
TI  - Analysis of anti-Trypanosoma cruzi antibody isotype specificities by western blot
      in sera from patients with different forms of Chagas' disease.
AB  - Infection of humans with Trypanosoma cruzi leads to either a lifelong
      asymptomatic infection or to symptomatic presentations such as cardiomyopathy,
      mega-syndromes, or both. The reasons for the different clinical manifestations
      are not understood. We have previously studied a group of chronically infected
      individuals with different clinical forms of Chagas' disease and found that the
      levels of some anti-T. cruzi antibody isotypes, analyzed by enzyme-linked
      immunosorbent assay, differed among patients with different clinical
      presentations. We have expanded these studies to examine the antigen specificity
      of these patients' IgG1, 2, 3, IgM, and IgA by western blot. We observed that
      binding of particular antigens by some antibody isotypes were more prevalent in
      some clinical groups as compared to others. For example, IgG3 from 13 of 19 (68%)
      individuals with digestive manifestations bound a 68-kDa antigen, but only 3 of
      31 (9%) individuals with cardiac involvement detected this same moiety. We also
      found that, regardless of the clinical group, the profiles of antigens recognized
      by each antibody isotype differs dramatically from the profiles recognized by
      each other isotype. Together with our previous observations demonstrating that
      the levels of anti-parasite antibody isotypes correlates with the clinical form,
      these data suggest that overall anti-T. cruzi antibody reactivities may indeed be
      skewed toward different antigens in individuals with different clinical
      presentations.

PMID- 9645879
TI  - Reduced expression of lipophosphoglycan (LPG) and kinetoplastid membrane protein
      (KMP)-11 in Leishmania donovani promastigotes in axenic culture.
AB  - The expression of surface lipophosphoglycan (LPG) and the lipophosphoglycan
      associated kinetoplastid membrane protein (KMP)-11 was studied in the strain AG83
      of Leishmania donovani in axenic culture. The expression of LPG and KMP-11
      decreased along with parasite virulence as a function of the time of the
      subculture.

PMID- 9645880
TI  - Ancylostoma duodenale is responsible for hookworm infections among pregnant women
      in the rural plains of Nepal.
AB  - Fecal specimens from 292 pregnant women (ages 15-40 yr) and 129 infants (ages 10
      20 wk) were examined for helminth eggs by the Kato-Katz method and cultured for
      helminth larvae identification using a modified Harada Mori method. These
      specimens were collected from June 1995 through July 1996 in Sarlahi District in
      the southern rural plains of Nepal. Among pregnant women, the prevalence of
      helminth infection by the Kato-Katz method was 78.8%, 56.2%, and 7.9% for
      hookworm, Ascaris lumbricoides, and Trichuris trichiura, respectively. Using the
      modified Harada-Mori method, 66.1% and 2.0% of women's fecal cultures were
      positive for hookworm and Strongyloides stercoralis, respectively. All of the
      cultured hookworm larvae were identified as Ancylostoma duodenale. Among infants,
      1 specimen was positive for hookworm and 1 for A. lumbricoides using the Kato
      Katz method. The modified Harada Mori method detected no larvae in specimens from
      infants. There was 81.8% agreement between the 2 methods for the detection of
      hookworm infection. Ancylostoma duodenale is endemic in this study population and
      highly prevalent in pregnant women.

PMID- 9645881
TI  - Antigenic similarity between Hammondia hammondi and Toxoplasma gondii
      tachyzoites.
AB  - Hammondia hammondi is an obligate heteroxenous intestinal coccidian of cats,
      sharing many characteristics with Toxoplasma gondii. The tachyzoite stage
      antigens of T. gondii and H. hammondi were studied by immunofluorescence assays
      (IFA) and western blotting (WB) techniques to demonstrate antigenic similarities.
      Five monoclonal antibodies (MAbs), anti-T. gondii antigens, P22, P23, P30, P35,
      and P43, and mice polyclonal anti-H. hammondi serum were investigated. Antigens
      of H. hammondi were recognized by anti-P30 MAb both in IFA and in WB and by anti
      P22 and anti-P35 MAbs only in IFA. Polyclonal anti-H. hammondi serum revealed
      many common antigens between the 2 parasites (30, 32, 35, 66, and 90 kDa). The
      differences of host parasite relationship between these 2 coccidians lead us to
      suggest that many of these antigens with similar molecular weights are not the
      same, but homologous, molecules or that they are not the only factors involved in
      these differences.

PMID- 9645882
TI  - A chicken anti-conoid monoclonal antibody identifies a common epitope which is
      present on motile stages of Eimeria, Neospora, and Toxoplasma.
AB  - The chicken monoclonal antibody (mAb) 6D12-G10, raised against Eimeria acervulina
      sporozoites, has previously been shown to recognize the conoid of E. acervulina
      sporozoites and inhibit sporozoite invasion of lymphocytes in vitro. In indirect
      immunofluorescent assay, the mAb 6D12-G10 also reacted with merozoites from E.
      acervulina and identified a 21-kDa merozoite protein on western blots. By
      confocal laser scanning microscopy, the conoid of sporozoites from 6 different
      avian Eimeria species (E. brunetti, E. maxima, E. mitis, E. necatrix, E. praecox,
      and E. tenella) were reactive with 6D12-G10 mAb. Furthermore, the 6D12-G10 mAb
      also showed cross-reactivity with motile stages of 2 closely related
      apicomplexans, Neospora, and Toxoplasma. These results indicate that the mAb 6D12
      G10 identifies a conserved epitope on the conoid that is important in host cell
      invasion by the apicomplexan parasites.

PMID- 9645883
TI  - Efficacy of moxidectin 2% oral gel against second- and third-instar Gasterophilus
      intestinalis De Geer.
AB  - In a trial designed to evaluate the efficacy of the recommended dosage of
      moxidectin 2% oral gel against the gastric stages of Gasterophilus spp., 14
      ponies were selected from a herd on the basis of the inclusion criterion of the
      presence of Gasterophilus spp. eggs attached to their hair coats. After random
      allocation, the ponies were treated with 1 of 2 treatments, moxidectin 2% equine
      gel in a single dose at the commercial dosage of 400 microg moxidectin/kg body
      weight or placebo gel. The animals were necropsied 14 days posttreatment.
      Efficacies against second- and third-instar Gasterophilus intestinalis De Geer
      were 100% and 99.5%, respectively.

PMID- 9645884
TI  - Experimental transmission of the nematode Echinomermella matsi to the sea urchin
      Strongylocentrotus droebachiensis in the laboratory.
AB  - Three experiments were conducted to investigate the possibility of maintaining
      the Echinomermella matsi-Strongylocentrotus droebachiensis system in the
      laboratory. The experiments were performed by injecting E. matsi larvae taken
      directly from gravid female nematodes into the mouths of sea urchins. In all
      experiments, this treatment resulted in a higher infection in treated animals
      than in unmanipulated controls. The successful establishment of larvae indicates
      that E. matsi has a monoxenous life cycle. The growth of larvae in experimentally
      infected hosts was slow, indicating that the generation time of the parasite is
      of the same magnitude as the life expectancy of the host, 1-2 yr. This slow
      growth rate suggests that considerable resources will be needed to maintain the
      system in the laboratory.

PMID- 9645885
TI  - Sarcocystis-associated encephalitis and myocarditis in a wild turkey (Meleagris
      gallopavo).
AB  - A Sarcocystis-like organism was associated with encephalitis and myocarditis in
      an ataxic, emaciated adult male turkey (Meleagris gallopavo) from Gilmer County,
      West Virginia. Protozoal schizonts and merozoites were associated with areas of
      inflammation and occasionally necrosis in both the heart and the brain. The
      organisms divided by endopolygeny and stained positively with anti-Sarcocystis
      cruzi serum in an immunohistochemical test.

PMID- 9645886
TI  - Twenty-two-year follow-up in the VA Cooperative Study of Coronary Artery Bypass
      Surgery for Stable Angina.
AB  - We evaluated the 22-year results of initial coronary artery bypass surgery with
      saphenous vein grafts compared with initial medical therapy on survival,
      incidence of myocardial infarction, reoperation, and symptomatic status in 686
      patients (average age 51) with stable angina in the Veterans Affairs Cooperative
      Study of Coronary Artery Bypass Surgery. Between 1972 and 1974, 354 patients were
      assigned to medical treatment and 332 to surgical revascularization. In the
      surgical cohort, 312 patients underwent operation (operative mortality 5.8%) and
      25% subsequently underwent repeat operation (operative mortality 10.3%). In the
      medical cohort, 160 patients crossed over to surgery (operative mortality 4.4%)
      and 21% of these patients had reoperation (operative mortality 9.1%). Neither
      crossover nor reoperation was predictable by angiographic or clinical risk
      factors measured at baseline. The overall 22-year cumulative survival rates were
      25% and 20% in the medical and surgical cohorts (p = 0.24). Corresponding rates
      in low-risk patients who had 1 or 2 vessels diseased, or 3 vessels diseased with
      normal left ventricular function were 31% and 24% (p = 0.024). Although
      significant at 10 years, there was also no long-term survival benefit for high
      risk patients assigned to bypass surgery. The probabilities of remaining free of
      myocardial infarction and of being alive without infarction were significantly
      higher with initial medical therapy, 57% versus 41% (p = 0.02) and 18% versus 11%
      (p = 0.0031), respectively. This trial provides strong evidence that initial
      bypass surgery did not improve survival for low-risk patients, and that it did
      not reduce the overall risk of myocardial infarction. Although there was an early
      survival benefit with surgery in high-risk patients (up to a decade), long-term
      survival rates became comparable in both treatment groups. In total, there were
      twice as many bypass procedures performed in the group assigned to surgery
      without any long-term survival or symptomatic benefit.

PMID- 9645887
TI  - Comparison of results and risk factors of cardiac surgery in two 3-year time
      periods in the 1990s.
AB  - With the increasing number of treatment options for heart disease, decision
      making requires profiles of risk for conventional cardiac surgery. Refinements in
      techniques and clinical practices seem to have reduced surgical risk. This study
      was performed to determine current risk factors. From July 1, 1990, to June 30,
      1996, 1,036 consecutive patients underwent 1,042 heart operations using standard
      incisions and cardiopulmonary bypass with cardioplegia. Univariate and
      multivariate analyses using a logistic regression model were performed to
      determine factors significant for combined 30-day and hospital mortality. To
      determine if there were trends in the results and the risk factors, the last 500
      consecutive cases in the series were analyzed separately. Overall, 30-day
      mortality was 17 of 1,042 (1.6%) and combined 30-day and hospital mortality was
      27 of 1,042 (2.6%). Significant risk factors for combined 30-day and hospital
      mortality by multivariate analyses were: emergent/resuscitative status,
      preoperative dialysis, left ventricular ejection fraction < or = 30%, valve
      operation, and creatinine > or = 1.5 mg/dl. Comparison with baseline
      characteristics of the patients undergoing the last 500 consecutive operations to
      the earlier 542 operations in the study group showed that risk factors had a very
      similar profile for the 2 groups. The overall 30-day mortality for the last 500
      consecutive operations was 5 of 500 (1.0%) and combined 30-day and hospital
      mortality was 8 of 500 (1.6%). The significant risk factors by multivariate
      analyses were reduced to left ventricular ejection fraction < or = 30% and
      creatinine > or = 1.5 mg/dl. These results indicate that modern techniques and
      clinical practices have mitigated well-recognized risk factors in conventional
      cardiac surgery and this trend is ongoing.

PMID- 9645888
TI  - Prognostic role of troponin T versus troponin I in unstable angina pectoris for
      cardiac events with meta-analysis comparing published studies.
AB  - Controversy exists as to the clinical roles and relative specificities of cardiac
      troponin T or I in patients with unstable angina pectoris (UAP). We measured
      troponin T and I levels on admission in 123 patients with UAP. Of the 107
      patients with normal creatine kinase during the first 24 hours, troponin T and I
      were elevated in 14 and 13 patients, respectively. At 30 days, 5 of 14 patients
      (36%) with elevated troponin T and 3 of 93 patients (3.2%) with normal troponin T
      had acute myocardial infarction (odds ratio [OR], 16.7; 95% confidence interval
      [CI] 3.4 to 81.5; p <0.001). Of 13 patients with elevated troponin I, 5 patients
      (39%) and 3 of 94 patients (3.2%) with normal troponin I had acute myocardial
      infarction (odds ratio, 21.7; 95% CI 4.3 to 110; p <0.001). No deaths occurred
      within 30 days. Both markers demonstrated equivalent sensitivity (63%) and
      specificities (troponin T: 91%; troponin I: 92%) for myocardial infarction. Meta
      analysis of 12 published troponin T and 9 troponin I studies in patients with UAP
      produced risk ratios of 4.2 (95% CI 2.7 to 6.4, p <0.001) for troponin I compared
      with 2.7 (95% CI 2.1 to 3.4, p <0.001) for troponin T. Comparison of the
      sensitivities and specificities of both markers using summary receiver operating
      characteristic curves showed no significant difference in their abilities to
      predict acute myocardial infarction and cardiac death. Troponin T and I show
      similar prognostic significance for acute myocardial infarction or death in the
      same patients with UAP. The 2 markers are equally sensitive and specific, as
      confirmed by meta-analysis, and this supports a role in risk stratification.

PMID- 9645889
TI  - Usefulness of pulse-wave Doppler tissue sampling and dobutamine stress
      echocardiography for the diagnosis of right coronary artery narrowing.
AB  - To study the feasibility and diagnostic accuracy of right coronary artery (RCA)
      narrowing by right ventricular (RV) pulse-wave Doppler tissue sampling during
      dobutamine stress echocardiography (DSE), 30 patients (mean age 55 +/- 9.5 years,
      26 men) with suspected coronary artery disease underwent DSE (up to 40
      microg/kg/min with additional atropine during submaximum heart rate responses).
      Pulse-wave Doppler tissue sampling of RV free walls close to the tricuspid
      annulus was performed in the apical 4-chamber view. The maximum velocity during
      the ejection phase, early, and late diastole was measured. Data from 5
      consecutive beats were averaged. The measurements were repeated at rest, at low
      dose (10 microg/kg/min), and at peak dobutamine stress. The results were
      evaluated for the prediction of significant proximal or medium RCA narrowing (>
      or = 50% diameter stenosis, assessed by quantitative coronary angiography within
      the previous 3 months). A progressive increase of the ejection phase velocity (>
      25% between 10 microg/kg/min and peak stress) was predictive of a normal RCA,
      whereas a blunted increase and/or decrease (< 25% of increase) was predictive of
      significant RCA narrowing: sensitivity (95% confidence intervals): 82% (68 to
      96), specificity: 78% (67 to 93), positive predictive value: 69% (52 to 86),
      negative predictive value: 88% (75 to 100), accuracy: 79% (65 to 94). Pulse-wave
      Doppler tissue sampling provided analyzable data in 100%, whereas the visual
      assessment of gray-scale images was possible only in 90%. Thus, in patients with
      suspected RCA narrowing, pulse-wave Doppler tissue sampling during DSE was able
      to diagnose significant RCA narrowing.

PMID- 9645890
TI  - Effects of practice setting on quality of lipid-lowering management in patients
      with coronary artery disease.
AB  - We undertook a study to determine whether there were differences in the quality
      of lipid management in patients with coronary artery disease (CAD) in 2 different
      practice settings (which represent different socioeconomic classes), and to
      determine the level of compliance with the National Cholesterol Education Program
      guidelines by academic physicians in managing patients with CAD. A retrospective
      cross-sectional study was performed using a systematic chart review of 270
      medical records (131 from the cardiology clinic, 139 from the cardiology private
      practice) of patients with known CAD at an academic tertiary care center in New
      York City. The total proportion of patients with CAD having a lipid profile
      ordered in the clinic and private suite was 43%. Of these people, 22% had a low
      density lipoprotein cholesterol (LDL) < or = 100 mg/dl and 54% had an LDL < or =
      130 mg/dl (10% and 23% of the total population, respectively). The total
      proportion of patients taking lipid-lowering medications was 29%. When comparing
      the quality of treatment between the 2 settings, there were no statistically
      significant differences in the percentages of patients who had lipid profiles
      measured (40% clinic vs 47% private suite, p >0.10), in the percentage of
      patients with LDL < or = 130 mg/dl (50% clinic vs 57% private suite, p >0.10) or
      in the weighted percentage of patients taking lipid-lowering medications (29%
      clinic vs 48% private suite, p = 0.099). The performances of individual
      physicians, however, varied widely. The percentages of patients with lipid
      profiles measured by individual physicians ranged from 0% to 83%, while the
      percentages of patients on drug treatment by a physician ranged between 10% and
      88%. These findings indicate that socioeconomic differences, represented by
      different practice settings, do not account for differences in the screening for,
      control of, or use of medications in managing hyperlipidemia. Rather, individual
      physicians are accountable for differences in lipid management.

PMID- 9645891
TI  - Cardiac release and kinetics of endothelin after uncomplicated percutaneous
      transluminal coronary angioplasty.
AB  - This study was designed to assess the release kinetics of endothelin after
      percutaneous transluminal coronary angioplasty (PTCA) and to prove the coronary
      endothelium as the source of the endothelin release. Twenty-seven patients with
      single-vessel coronary artery disease underwent PTCA. Endothelin, troponin T,
      myoglobin, and creatine phosphokinase paired blood samples were withdrawn from
      the coronary sinus and a peripheral vein before the balloon maneuver and at 1, 5,
      10, 30, 45 minute(s), and at 1, 2, 3, 6, 12, and 24 hour(s) after the last
      balloon maneuver. Myocardial ischemia was monitored by means of cardiac lactate
      metabolism and 12-lead electrocardiogram. Thirteen patients who underwent a
      diagnostic cardiac catheterization served as a control group. In the left
      coronary artery, PTCA (n = 19) endothelin concentrations increased from 4.1 pg/ml
      as a common mean baseline level before intervention to 13.9 +/- 2.6 pg/ml (mean
      +/- SD) in the coronary sinus and 7.9 +/- 2.2 pg/ml (mean +/- SD) in the
      peripheral vein at 1 minute after the intervention (p <0.001). The levels
      remained elevated for 3 hours with higher coronary sinus than peripheral venous
      concentrations due to persistent cardiac endothelin release. PTCA of the right
      coronary artery (n = 8) also led to an instantaneous endothelin increase from a
      mean concentration of 4.4 before intervention to 8.3 pg/ml after intervention
      with identical coronary sinus and peripheral venous levels (p <0.001). Endothelin
      levels gradually decreased to normal within 6 hours. No patient developed a
      measurable myocardial ischemia or a myocardial infarction. In the control group
      all parameters remained unchanged. Uncomplicated PTCA was followed by a
      significant cardiac endothelin release that seems to indicate endothelial injury
      and not myocardial ischemia.

PMID- 9645892
TI  - Quantitative angiography of coronary artery dimensions 24 hours after rotational
      atherectomy.
AB  - Rotational atherectomy results in platelet activation and heat generation, which
      may impact artery size immediately after treatment. In addition, arteries treated
      with balloon angioplasty may exhibit recoil within 24 hours. In this study,
      arteries treated with rotational atherectomy, with and without adjunctive balloon
      angioplasty, were analyzed by quantitative coronary angiography to determine the
      effect of rotational atherectomy on the dynamic behavior of the arterial wall
      within 24 hours after the procedure. Quantitative coronary angiography was
      performed at a core laboratory. Coronary angiogram acquisitions were preceded by
      intracoronary nitroglycerin injections and were repeated using identical angles
      of projection. Proximal and distal reference vessel diameters were 2.55 +/- 0.60
      and 2.28 +/- 0.51 mm, respectively, and did not change from pre- to
      postprocedure. Both were larger the following day increasing to 2.72 +/- 0.65 and
      2.52 +/- 0.52 mm, respectively, (p <0.001). Minimum luminal diameter (MLD)
      increased from 0.70 +/- 0.28 mm before to 1.49 +/- 0.34 mm after the procedure
      and to 1.72 +/- 0.37 mm at 24-hour follow-up (p <0.001). Subset analysis of
      patients treated with rotational atherectomy alone or rotational atherectomy with
      adjunctive balloon angioplasty revealed that the increase in luminal diameters
      occurred in both subsets. Patients treated with adjunctive angioplasty had a
      smaller initial MLD, a larger postprocedure MLD, and no difference in MLD at 24
      hour follow-up compared with stand-alone rotational atherectomy. Subset analysis
      of 100 patients who had 6-month follow-up angiography revealed that both a
      calculated acute gain and chronic late loss, based on a 24-hour film, differed
      significantly from values using a film acquired immediately after the procedure.
      However, the slope of the linear regression between acute gain and chronic late
      loss did not differ. Coronary arteries treated with rotational atherectomy with
      or without adjunctive balloon angioplasty increase significantly in size during
      the first 24 hours after the procedure. This phenomenon has implications for the
      calculation of absolute gain and chronic late loss, but not for the linear
      relation between the 2 quantitative outcomes.

PMID- 9645893
TI  - Do physicians modify their prehospital management of patients in response to a
      public campaign on chest pain?
AB  - The goals of this study were to analyze the impact of a public campaign on chest
      pain on physicians involved in the prehospital care of patients with this
      symptom, in terms of physician delay, rates of immediate hospitalization, and of
      transportation by ambulance. Prehospital delays and decisions for all 866
      patients with chest pain managed by the community and generalist physicians or by
      emergency physicians, who presented to the emergency department of a teaching
      hospital during the 12 months of the campaign, were compared with those of all
      749 patients with similar presentations during the 12 months before it. When
      community and generalist physicians were involved, median (110 minutes) physician
      delay did not decrease during the campaign, whereas it decreased from 65 to 56
      minutes (p <0.003) when emergency physicians were involved. Rates of immediate
      hospitalization (73%) and of transportation by ambulance (47%) of patients
      managed by community and generalist physicians were unaffected by the campaign,
      whereas they increased from 96% and 89%, respectively, to 98% (p = 0.09) and 94%
      (p <0.02) when emergency physicians were involved. Similar observations were made
      in patients with confirmed acute myocardial infarction and unstable angina and
      remained highly significant after adjustment for differences in clinical
      characteristics. Thus, community and generalist physicians did not significantly
      modify their prehospital management of patients with chest pain despite a public
      campaign. To be successful, guidelines on the matter have to be developed with
      the active participation of these physicians.

PMID- 9645894
TI  - Frequency analysis of human atrial fibrillation using the surface
      electrocardiogram and its response to ibutilide.
AB  - This study assesses a technique for quantifying the frequency spectrum of atrial
      fibrillation (AF) using the surface electrocardiogram. Electrocardiograhic
      recordings were obtained in 61 patients during AF. After bandpass filtering, the
      QRST complexes were subtracted using a template-matching algorithm. The resulting
      fibrillatory baseline signal was subjected to Fourier transformation and
      displayed as a frequency power spectrum. These frequency spectra were compared to
      direct measurements from the right atrium and coronary sinus in 35 patients
      undergoing electrophysiologic study. The clinical use of this technique was
      explored by correlating fibrillatory frequency with the behavior of the
      arrhythmia in 26 patients referred for cardioversion. The electrocardiographic
      frequency spectrum during AF was characterized by a single peak that varied
      widely between patients (range 228 to 480 beats/min). There was a strong
      correlation between electrocardiographic peak frequency and that measured in the
      right atrium and coronary sinus (r = 0.79 to 0.98, p <0.0001). Episodes of AF
      that terminated in < 5 minutes had a lower frequency than those that persisted >
      5 minutes (324 +/- 36 vs 402 +/- 78 beats/min, p = 0.001). Chronic AF (< 3 months
      in duration) had a lower frequency than chronic AF (present > 3 months) (336 +/-
      48 vs 408 +/- 60 beats/ min, p = 0.012). Fibrillation frequency was an accurate
      predictor of conversion with ibutilide. Success rate was 100% in patients with
      peak frequency < 360 beats/min versus 29% in patients with frequencies > or = 360
      beats/min (p = 0.003). Automatic analysis of the frequency content of the
      fibrillatory baseline on the surface electrocardiogram accurately reflects the
      average rate of AF. This measurement correlates with the clinical pattern of the
      arrhythmia and predicts the response to administration of ibutilide.

PMID- 9645895
TI  - Echocardiographic parameters for predicting maintenance of sinus rhythm after
      internal atrial defibrillation.
AB  - Chronic atrial fibrillation (AF), which is refractory to external electrical
      direct current shock and/or pharmacologic cardioversion, may be successfully
      cardioverted using internal atrial defibrillation. To avoid unnecessary
      procedures, it is important to be able to predict which patients will revert to
      AF. Thirty-eight patients with chronic AF underwent successful internal atrial
      defibrillation and were followed for 6 months after restoration of sinus rhythm.
      Left atrial (LA) diameter, left ventricular ejection fraction, maximum LA
      appendage area, and peak emptying velocities of the LA appendage were analyzed to
      determine which of these factors were associated with recurrence of AF. Forty
      nine percent of patients had a recurrence of AF within 6 months following
      internal atrial defibrillation. The preprocedural ejection fraction (mean +/- SD
      59 + 14% vs 57 + 13%, p = 0.63), LA diameter (4.2 +/- 0.6 cm vs 4.5 +/- 0.6 cm, p
      = 0.16), and LA appendage area (5.0 +/- 1.5 cm2 vs 5.8 +/- 1.5 cm2, p = 0.13) did
      not differ significantly between patients who maintained sinus rhythm and those
      who had recurrence of AF. Peak emptying velocities of the LA appendage before
      cardioversion were significantly lower in patients with recurrence of AF compared
      with patients who maintained sinus rhythm (0.26 +/- 0.1 m/s vs 0.49 +/- 0.17 m/s,
      p = 0.001). A peak emptying velocity <0.36 had a sensitivity of 82% and a
      specificity of 83% for predicting recurrence of AF.

PMID- 9645896
TI  - Prospective comparison of flecainide versus sotalol for immediate cardioversion
      of atrial fibrillation.
AB  - This study sought to compare the efficacy and safety of intravenous flecainide
      and sotalol for immediate cardioversion of atrial fibrillation. We performed a
      prospective, randomized, single-blind, multicenter trial, including 106
      hemodynamically stable patients with atrial fibrillation, stratified according to
      duration of the arrhythmia. Exclusion criteria included severely reduced left
      ventricular systolic function, recent antiarrhythmic therapy, and hypokalemia.
      Patients were randomly assigned to receive either intravenous flecainide or
      intravenous sotalol. Trial medication was given at a dose of 1.5 mg/kg body
      weight (maximum 150 mg). Overall, 28 of 54 patients (52%) given flecainide and 12
      of 52 patients (23%) given sotalol converted to sinus rhythm during the first 2
      hours after start of the infusion (p = 0.003). Multivariate analysis confirmed
      that treatment allocation to flecainide, an arrhythmia duration of < or = 24
      hours, higher plasma magnesium level at baseline, higher age for men, and lower
      age for women independently increases the probability of conversion. The
      frequency of adverse effects was not significantly different in the 2 treatment
      groups.

PMID- 9645897
TI  - Effect of beta-blocker therapy in patients with coronary artery disease in New
      York Heart Association classes II and III. The Bezafibrate Infarction Prevention
      (BIP) Study Group.
AB  - The aim of the study was to investigate the effect of beta-blocker treatment on a
      large cohort of patients with coronary artery disease in functional classes II
      and III according to the New York Heart Association (NYHA) classification. Among
      11,575 patients with coronary artery disease screened for participation, but not
      included in the Bezafibrate Infarction Prevention (BIP) study, 3,225 (28%) were
      in NYHA classes II and III. In the latter group of patients we compared the
      prognosis of 1,109 (34%) treated with beta blockers with 2,116 counterparts not
      receiving beta-blocker therapy. After a mean follow-up of 4 years, all-cause and
      cardiac mortality rates were significantly lower among beta-blocker users, 9% and
      5%, respectively, than among beta-blocker nonusers, 17% and 11%, respectively (p
      <0.01 for both). After multivariate adjustment, treatment with beta blockers was
      associated with a lower all-cause mortality risk (hazards ratio [HR] 0.62, 95%
      confidence interval [CI] 0.49 to 0.78), and a lower cardiac mortality risk (HR =
      0.61, 95% CI 0.45 to 0.83) than was no treatment with a beta blocker. Lower total
      mortality risk was noted among patients in NYHA class II (HR 0.63, 95% CI 0.48 to
      0.82) and in NYHA class III (HR 0.57, 95% CI 0.37 to 0.87) as well as in patients
      with (HR 0.62, 95% CI 0.48 to 0.81) or without (HR 0.70, 95% CI 0.45 to 1.09) a
      previous myocardial infarction. We conclude that beta-blocker therapy in coronary
      patients in NYHA classes II or III is safe and associated with a lower risk for
      all-cause and cardiac mortality.

PMID- 9645898
TI  - Osteitis deformans (Paget's disease) and calcific disease of the heart valves.
AB  - The prevalence of calcific aortic valve stenosis in Paget's disease (osteitis
      deformans) was investigated by reviewing autopsy data of severe cases (> or = 75%
      involvement of > or = 3 major bones, the femur, tibia, skull, and pelvis) and
      moderate cases (> or = 75% involvement of only 1 or 2 major bones) of Paget's
      disease. Comparisons were made with normal age-matched controls. Aortic stenosis
      (AS) was present in 24% of 27 autopsies of severe Paget's disease compared with
      3.5% in 201 controls (p <0.01). Clinical signs of AS were present in 39% of 102
      patients with severe Paget's disease compared with 4% in 417 controls (p <0.101).
      The prevalence of AS in 18 cases of moderate Paget's disease was similar to that
      of controls. Electrocardiograms were reviewed in 45 cases of Paget's disease and
      compared with 80 controls of similar age. Complete atrioventricular (AV) block,
      incomplete AV block, bundle branch block, and left ventricular hypertrophy were
      present in 11%, 11%, 20%, and 13% of the Paget's cases and in only 2.5%, 1.3%,
      2.5%, and 3.8% in the control cases (p <0.05, <0.05, <0.01, and <0.05,
      respectively). It is concluded that in severe Paget's disease there is a high
      prevalence of AS, heart block, and bundle branch block, but these are not present
      in moderate degrees of bone involvement.

PMID- 9645899
TI  - Left ventricular systolic torsion and early diastolic filling by echocardiography
      in normal humans.
AB  - This study describes a novel 2-dimensional echocardiographic technique to measure
      left ventricular (LV) systolic twist in humans and relates this measure to early
      ventricular filling. LV twist is the counterclockwise rotation of the left
      ventricle during systole when viewed from the apex. The effect of ventricular
      twist has been postulated to store potential energy, which ultimately aids in
      diastolic recoil, leading to ventricular suction. The generated negative early
      diastolic pressures may augment early ventricular filling. We measured
      ventricular twist in 40 patients with normal transthoracic echocardiograms. End
      systolic twist was determined by measuring rotation of the anterolateral
      papillary muscle about the center of the ventricle. LV filling was assessed by
      analysis of transmitral Doppler flow velocities. The mean value obtained was 9 +/
      7 degrees of rotation. Twist measurements were highly reproducible with an
      intraobserver correlation coefficient of r = 0.881, p <0.001. The magnitude of
      ventricular twist was strongly correlated positively with acceleration of the
      mitral E-wave (r = 0.75; p <0.0001) and negatively with the mitral E-wave
      acceleration time (r = -0.83; p <0.0001).

PMID- 9645900
TI  - Colles-Stokes contributions to the concept of heart failure.
AB  - "Colles fracture," "Colles law," "Stokes-Adams syndrome," "Cheyne-Stokes
      respiration," and "Corrigan pulse" are some of the contributions of the Irish
      school that are utilized for teaching purposes in medical schools and training
      programs, as well as in daily practice of medicine. We wish to add an important
      description by Drs. Colles and Stokes that personifies the considerable personal
      contributions of these 2 physicians in our understanding of the pathophysiologic
      expression of the syndrome of heart failure. The clinical-pathologic correlation
      of the disease that affected Dr. Colles is well described by Dr. Stokes in his
      treatise Diseases of the Heart and the Aorta. He recognized the cyclical nature
      of frequent decompensations in heart failure, the relation of clinical worsening
      in conjunction with reduced urine output, as well as the importance of
      reestablishing urinary flow to achieve a decrease in dyspnea. Dr. Colles also
      demonstrated a profound clinical insight when he noticed, first, that his
      affliction was "eventually a fatal disease and that remedies that work may lose
      effect over time," illustrating an observation that has stood the test of time
      and, secondly, when he told Dr. Smith "... I would direct particular attention to
      the heart and the lungs ... and the swelling in the right hypochondrium ... I
      suspect that there is some connexion between this swelling of the hypochondrium
      and the diseased state of the heart." We believe that the Colles-Stokes
      contributions, both in the clinical as well as the clinical-pathologic arenas,
      are one of the landmark descriptions that helped to evolve the concept of the
      syndrome of heart failure.

PMID- 9645901
TI  - Robert Ogden Bonow, MD: a conversation with the editor. Interview by William
      Clifford Roberts..

PMID- 9645902
TI  - Impact of exercise single-photon emission computed tomographic imaging on
      appropriateness of coronary revascularization.
AB  - This study examined the predictors of early coronary revascularization in 816
      patients with chest pain syndromes who had coronary artery disease by angiography
      and exercise single-photon emission computed tomography (SPECT) thallium imaging.
      Multivariate analysis of clinical, stress, nuclear, and catheterization variables
      revealed the presence of SPECT reversibility as the most powerful predictor (chi
      square = 43) of early revascularization.

PMID- 9645903
TI  - Usefulness of technetium-99m sestamibi infarct size in predicting posthospital
      mortality following acute myocardial infarction.
AB  - In this multicenter study, 249 patients who underwent tomographic technetium-99m
      sestamibi infarct size measurement at hospital discharge were followed up for a
      median duration of 7 months. Infarct size was significantly associated with
      mortality (chi-square = 5.8, p = 0.02) and could stratify patients into lower and
      higher risk subsets: 1-year mortality 2% for infarct size < 14% versus 8% for
      infarct size > or = 14% of the left ventricle.

PMID- 9645904
TI  - Inhaled nitric oxide improves exercise capacity in patients with severe heart
      failure and right ventricular dysfunction.
AB  - Fourteen cardiac transplant candidates were studied with cardiopulmonary exercise
      testing at baseline and while breathing nitric oxide (40 ppm). Oxygen consumption
      at the anaerobic threshold was improved by breathing nitric oxide in patients
      with pulmonary hypertension and in patients with an elevated left ventricular end
      diastolic volume index.

PMID- 9645905
TI  - Reproducibility of the six-minute walking test in patients with chronic
      congestive heart failure: practical implications.
AB  - This study assesses the reproducibility of the 6-minute walking test in patients
      with chronic heart failure using 2 different measurement protocols. Practical
      suggestions for the clinical setting are given.

PMID- 9645906
TI  - Practices and attitudes concerning oral health in pediatric cardiology clinics to
      prevent infective endocarditis.
AB  - A survey of 121 pediatric cardiology clinics investigated the current practices
      and attitudes toward oral health education and oral screenings in pediatric
      cardiology clinics for patients susceptible to infective endocarditis. Most
      pediatric cardiology clinics do not provide oral health education and oral
      screenings, but believe it would be beneficial.

PMID- 9645907
TI  - Improved clinical effectiveness with a collagen vascular hemostasis device for
      shortened immobilization time following diagnostic angiography and percutaneous
      transluminal coronary angioplasty.
AB  - This study prospectively compared immobilization time followed by use of a
      vascular hemostasis device (VasoSeal) versus manual compression to achieve
      hemostasis at the arterial puncture after angiography and percutaneous
      transluminal coronary angioplasty (PTCA). The trial shows that use of a vascular
      hemostasis device results in earlier mobilization, even in highly anticoagulated
      PTCA patients compared with manual compression, with no statistically significant
      complications.

PMID- 9645908
TI  - PR-segment deviation as the initial electrocardiographic response in acute
      pericarditis.
AB  - PR-segment deviations precede classic ST(J) deviations in acute pericarditis
      because the superficial myocarditis producing electrocardiographic changes is
      more encompassing in the thin atrial muscle. In patients with appropriate
      syndromes, PR-segment deviations should be recognized early after onset, as ST
      changes may be absent.

PMID- 9645909
TI  - Determination of pretest probability for detection of a cardiovascular source of
      emboli by transesophageal echocardiography using clinical and transthoracic
      echocardiographic data.
AB  - Transesophageal echocardiographic findings and their effect on disease management
      were evaluated in 216 patients with suspected cardiovascular source of emboli.
      Clinical and transesophageal echocardiographic findings were useful in defining
      pretest probability for finding a probable cardiovascular source of emboli on
      transesophageal echocardiography.

PMID- 9645910
TI  - A World Wide Web site for low-density lipoprotein receptor gene mutations in
      familial hypercholesterolemia: sequence-based, tabular, and direct submission
      data handling.
AB  - Familial hypercholesterolemia is an autosomal dominant inherited condition
      characterized by a mutation in the low-density lipoprotein receptor (LDLR) gene.
      A database has been set up on the World Wide Web for mutations in the LDLR gene.

PMID- 9645911
TI  - Effect of mitral regurgitation on thromboembolic risk in patients with rheumatic
      mitral valve disease.

PMID- 9645912
TI  - Interrupted inferior vena cava in asplenia syndrome.

PMID- 9645913
TI  - Evaluation of a modified APTT-based method for determination of APC resistance in
      plasma from patients on heparin or oral anticoagulant therapy.
AB  - An APTT-based kit method (Coatest APC Resistance), modified by predilution 1+4 of
      sample plasma in a plasma diluent containing a heparin antagonist (V-DEF plasma),
      has been evaluated on plasmas from patients treated with unfractionated (n = 110)
      or either of three different low molecular heparins (n=44), or with oral
      anticoagulants (n=147). Irrespective of treatment, no difference was observed in
      the APC response as compared to untreated individuals (n=62), and a complete
      discrimination was obtained between individuals with a normal factor V genotype
      and those carrying the FV:Q506 mutation. Furthermore, in contrast to the
      original, APTT-based kit method, where anticoagulant therapy results in a
      prolongation of the APTT, the modified kit provided APTT values within the normal
      range for orally anticoagulated (INR< or =6) and for all heparin treated (< or =1
      IU/mL) patients except for one with a suspected presence of phospholipid
      antibodies. Due to the predilution in V-DEF plasma, contamination with platelets
      up to 1.5 x 10(4)/microL had a negligible effect on analysis of frozen plasmas
      regarding their classification as normal or abnormal. Analyses of fresh plasmas
      show no influence at platelet counts up to 6x10(4)/microL. Consequently,
      negligible differences in APC ratios were obtained between fresh and frozen
      plasmas. In conclusion, the modified kit method is applicable to plasmas from
      anticoagulated patients as well as from untreated individuals, allowing a safe
      assignment regarding the presence or absence of the FV:Q506 genotype.

PMID- 9645914
TI  - The Arg506Gln mutation (FV Leiden) among a cohort of 4188 unselected Danish
      newborns.
AB  - Resistance to activated protein C (APC) is the most prevalent single phenomenon
      associated with thromboembolic disease. It is caused by a single point mutation
      in the factor V gene (Arg506Gln or FV Leiden), replacing an Arg506 with a Gln at
      the APC-cleavage site in factor V. In this study we present a prevalence study of
      the Arg506Gln mutation in a large Danish cohort. By screening 4188 newborns (8376
      alleles) we identified 3.4% alleles (95% CI: 3.0-3.8) of the Arg506Gln mutation,
      corresponding to a heterozygous prevalence of 6.6% (95% CI: 5.9-7.4) in Denmark.
      This is significantly lower than what has been reported from southern Sweden. The
      birth cohort has been selected from the entire country, providing representative
      and accurate estimates of the gene frequencies. Equal gender distribution was
      found, and the Arg506Gln mutation is probably not a considerable risk factor in
      fetal life in the general population.

PMID- 9645916
TI  - Mathematical model for the blood coagulation prothrombin time test.
AB  - A mathematical model for the prothrombin time test is proposed. The time course
      of clotting factor activation during coagulation was calculated, and the
      sensitivity of the test to a decrease in the concentrations of coagulation
      proteins or their activities was studied. The model predicts that only severe
      coagulation disorders connected with a more than five-fold decrease in the
      concentrations or activities of the blood coagulation factors can be revealed by
      the test.

PMID- 9645915
TI  - Oral antiplatelet efficacy of the platelet GPIIb/IIIa antagonist, DMP754 in non
      human primates.
AB  - Binding kinetic studies with XV459, the active form of DMP754, demonstrated
      comparable binding kinetics (Kd and Koff) with platelets obtained from either
      human or baboons which were different from that with platelets obtained from
      dogs. Therefore, the present study was undertaken to evaluate the antiplatelet
      efficacy of DMP754 following oral administration in baboons. The dose levels
      evaluated were 0.1 and 1.0 mg/kg, IV and 0.1, 0.3, 1.0, and 3.0 mg/kg, oral of
      DMP754. Oral doses of DMP754 resulted in dose- and time-related inhibition of
      platelet aggregation along with a modest effect on bleeding time prolongation.
      DMP754 at similar oral doses had 24 hours of antiplatelet effects in baboon as
      compared to 8-12 hours duration of antiplatelet efficacy in dogs. At maximal
      antiplatelet doses DMP754 demonstrated no significant effects on platelet count,
      clinical chemistry or hemodynamic profiles in baboons. These data suggest that
      DMP754 is a potent orally active antiplatelet agent with extended duration after
      once a day oral administration in non-human primate.

PMID- 9645917
TI  - Effects of various doses of antithrombin III on endotoxin-induced endothelial
      cell injury and coagulation abnormalities in rats.
AB  - We previously demonstrated that antithrombin III reduced the injury to
      endothelial cells caused by activated leukocytes in rats administered endotoxin.
      This occurred via the increase of the endothelial release of prostaglandin I2,
      which is a potent inhibitor of leukocyte activation. We evaluated the dose of
      antithrombin III required to prevent such endothelial cell injury in rats
      administered endotoxin, by comparing the effects of various antithrombin II doses
      on the pulmonary vascular injury. The intravenous administration of endotoxin, 5
      mg/kg, produced a transient accumulation of leukocytes in the lung, followed by
      pulmonary vascular injury, as indicated by an increase in the pulmonary vascular
      permeability, and coagulation abnormalities. The dose of 250 U/kg significantly
      inhibited all such effects of endotoxin. While lower doses of antithrombin III
      (50 and 100 U/kg) significantly inhibited such coagulation abnormalities, they
      failed to prevent either the pulmonary accumulation of leukocytes or the
      subsequent pulmonary vascular injury. Rats administered endotoxin exhibited an
      accumulation of neutrophils and edematous changes in the pulmonary interstitial
      space. Although such changes were reduced after 250 U/kg of antithrombin III,
      they were unaffected by lower doses of 50 and 100 U/kg. Plasma levels of 6-keto
      PGF1alpha were markedly increased in rats 90 min after the administration of
      endotoxin, and were significantly decreased in the endotoxin-treated rats
      administered the lower doses of antithrombin III (50 and 100 U/kg), but not
      altered in those endotoxin-treated rats receiving 250 U/kg of antithrombin III.
      These findings suggest that a higher antithrombin III dose is necessary to
      prevent endothelial cell injury than is required to inhibit coagulation
      abnormalities in an animal model of sepsis. These observations support the notion
      that antithrombin III may prevent endotoxin-induced endothelial cell injury by
      promoting endothelial release of prostaglandin I2 and thus inhibiting leukocyte
      activation.

PMID- 9645918
TI  - Postoperative plasma interleukin-6 in patients with renal cancer correlates with
      C-reactive protein but not with total fibrinogen or with high molecular weight
      fibrinogen fraction.
AB  - The concentration of fibrinogen (Fb) and its fractions, the levels of interleukin
      6 (I1-6), C-reactive protein (CRP), and immunoglobulin G (IgG) were determined in
      38 patients operated on because of renal cancer. The increased Fb and I1-6
      concentrations were found in approximately one-half of the patients with
      malignancy. The relations among the high molecular weight (HMW) and two low
      molecular weight (LMW and LMW') fibrinogen fractions in these patients before
      surgery did not differ from the corresponding relations in normal subjects. The
      levels of all (except IgG) compounds studied increased after surgery and the peak
      of I1-6 was observed on the first postoperative day but that of CRP on the third
      day. The concentrations of total Fb and of its HMW fraction were the highest also
      on the third postoperative day and this was in contrast with the decline of low
      molecular weight fractions at the same time. These variations of estimated
      variables can be regarded as being relevant to the acute phase response. We have
      noted a correlation between the maximal concentrations of I1-6 and CRP, but not
      between the corresponding concentrations of Il-6 and total Fb or HMW Fb; this may
      suggest that the concentration of Fb is also under the control of a factor other
      than I1-6.

PMID- 9645919
TI  - Factor II 20210 G-->A polymorphism associated to factor V Leiden: a report of two
      thrombophilic families.

PMID- 9645920
TI  - The Effect of the Simultaneous Addition of Molybdenum and Tungsten to the Culture
      Medium on the Formate Dehydrogenase Activity from Methylobacterium sp. RXM
AB  - Shake flask cultivation of the facultative methylotroph Methylobacterium sp. RXM
      was carried out by using a statistical experimental design to investigate the
      role of metal association on the formate dehydrogenase (FDH) levels. The maximal
      values of FDH activity were obtained for tungsten concentration up to 0.6 uM and
      for molybdenum concentration between 0.6 and 0.9 uM. The negative polynomial
      parameter (beta2) for tungsten compared with the positive polynomial parameter
      (beta1) for molybdenum on the FDH activity suggested that the latter metal exerts
      a stronger influence on the enzyme stimulation than the tungsten metal. A
      negative interaction between both metals was found, suggesting that tungsten and
      molybdenum shared an antagonistic effect on the enzyme activity.

PMID- 9645923
TI  - CO2 Emission in the 4-um Region.
AB  - From spectra recorded at a resolution of 0.020 cm-1 of the flame CH4 + O2 at low
      pressure, six new vibrational transitions in Deltav3 = 1 with 2v1 + v2 = 5 had
      been recently identified [D. Bailly et al., J. Mol. Spectrosc. 182, 10-17 (1996)]
      based on the HITRAN 92 predictions. New calculations have shown good consistency
      with our assignments except for one transition, namely, (21(1)1)3e --> (21(1)0)3e
      for which discrepancies (reaching 0.2 cm-1) were found. It has been possible to
      resolve this issue using new emission spectra of CO2, vibrationally excited by
      active nitrogen and recorded with a Fourier transform spectrometer at a
      resolution of 6.3 x 10(-3) cm-1 in the 4-5 um spectral region. Copyright 1998
      Academic Press.

PMID- 9645922
TI  - TNF, apoptosis and autoimmunity: a common thread?
AB  - A subset of cytokine mediators belonging to the tumor necrosis factor (TNF)
      family cause apoptosis, acting through receptors and signaling pathways that have
      recently come to light. Further, at least one autoimmune disease results from a
      defined defect of apoptosis (mutations of the Fas ligand or its receptor). It is
      offered that many, and perhaps most autoimmune diseases may result from primary
      defects of apoptosis. Such defects may cause reflexive overproduction of TNF and
      other pro-apoptotic cytokines. The collateral damage produced by these mediators
      may be of pathogenetic importance in complex autoimmune disorders such as
      rheumatoid arthritis and Crohn disease, wherein TNF blockade is known to have
      ameliorative effects.

PMID- 9645924
TI  - Nitrogen Broadening of Acetylene Lines in the nu5 Band at Low Temperature.
AB  - N2-broadening coefficients have been measured for 22 lines of C2H2 at 173.4 K in
      the P and R branches of the nu5 band, using a tunable diode-laser spectrometer.
      The lines with J values ranging from 1 to 29 are located in the spectral range of
      661-762 cm-1. The collisional widths obtained by Rautian profiles fitting closely
      the measured spectral shape of the lines are slightly larger than those derived
      from Voigt profiles. Semiclassical calculations of these broadenings have been
      performed by considering, in addition to electrostatic interactions, successively
      the atom-atom model and the Tipping-Herman intermolecular potential. The results
      obtained, which for some of them are in good agreement with the experimental
      data, depend significantly on the isotropic potential used to describe the
      trajectory model. By comparing broadening coefficients at room and low
      temperature, their temperature dependencies have been determined both
      experimentally and theoretically Copyright 1998 Academic Press.

PMID- 9645925
TI  - High-Resolution FTIR Study of the (nu3 + nu4, nu1 + nu4) Interacting System of
      Rovibrational Bands of PF3 Between 1100 and 1300 cm-1
AB  - With a resolution of 4.4 x 10(-3) cm-1, we were able to identify in this range
      the very weak nu2 + 2nu04 (A1) component near 1180 cm-1, the nu3 + nu4 band
      around 1205 cm-1 with its (A1 + A2) and E very intermixed components, and the nu1
      + nu4 (E) band centered at 1238 cm-1. Three thousand six hundred transitions
      belonging to the (nu3 + nu4, nu1 + nu4) interacting system were fitted together
      with a model taking into account l(2, 2) interactions inside nu1 + nu4 and
      between (A1 + A2) and E components of nu3 + nu4, the l-vibrational resonance
      inside nu3 + nu4(A1 + A2), and the Coriolis interactions between nu1 + nu4 and
      nu3 + nu4(A1 + A2) on one hand and between nu1 + nu4 and nu3 + nu4 (E) on the
      other. Four available MW transitions were also included in the fit. A rms of 0.76
      x 10(-3) cm-1 was obtained with 34 free parameters among 38. Normally the Fermi
      resonance, which links nu3 to nu2 + nu4 with a coupling term W234 = 2.86 cm-1,
      must connect each component of nu3 + nu4 with each component of nu2 + 2nu4. But
      since we have only little experimental information about the weak nu2 + 2nu04
      component (120 assigned lines) and none about the dark nu2 + 2nu+/-24 component,
      it was not possible to introduce this resonance in the fit. However, the
      bandcenters' shifts were calculated since the basic coupling term W234 and the
      anharmonic constant x24 are well known. Therefore, according to this
      approximation, the very sensitive anharmonic constants x34 and g34 could be
      deduced. Of course the x14 Fermi-independent constant, derived directly from the
      (nu1 + nu4)0 bandcenter given by the fit, was certainly more accurate. Copyright
      1998 Academic Press.

PMID- 9645926
TI  - Electronic States and Spectra of BiO.
AB  - The electronic spectrum of the BiO radical has been studied by Fourier transform
      emission spectroscopy, laser-induced fluorescence, and excimer laser photolysis
      techniques. Six new electronic states, A1 (Omega = 3/2) (Te = 11 528.8 cm-1,
      omegae = 530.4 cm-1, omegaexe = 2.42 cm-1), G (Omega = 3/2) (Te = 20 273 cm-1,
      omegae = 499 cm-1, omegaexe = 2.6 cm-1), H (Omega = 1/2) (Te = 20 469.76(6) cm-1,
      omegae = 471.63(18) cm-1, omegaexe = 2.153(35) cm-1), I (Omega = 1/2) (Te = 21
      982.50(2) cm-1, omegae = 506.50(11) cm-1, omegaexe = 3.263(34) cm-1), J (Omega =
      3/2) (Te = 25 598.95(42) cm-1, omegae = 489.95(16) cm-1, omegaexe = 2.309(45) cm
      1), and K (Omega = 1/2) (Te = 26 744.7(2) cm-1, omegae = 420.6(4) cm-1, omegaexe
      = 5.25(5) cm-1), and 14 new electronic transitions (A1 <-- X1, G --> X2, H left
      and right arrow X1, H --> A2(A), I left and right arrow X1, I --> A2, J left and
      right arrow X1, J left and right arrow X2, K left and right arrow X1, K left and
      right arrow X2, K --> A2, B left and right arrow X2, B --> A2, C left and right
      arrow X2) have been detected. Time-resolved measurements of the fluorescence
      decays have yielded the radiative lifetimes of the v = 0 levels of most states up
      to <30 500 cm-1 energy (tauX2 = 480 +/- 100 us, tauA2 = 9.3 +/- 1.5 us, tauH = 15
      +/- 3 us, tauI = 16 +/- 3 us, tauJ = 4.9 +/- 0.9 us, tauK = 2.6 +/- 0.3 us, tauB
      = 0.55 +/- 0.08 us, tauC = 0.84 +/- 0.15 us) and rate constants for quenching of
      the states by some rare gas atoms and simple molecules. The new electronic states
      A1, G, H, I, J, and K and the previously known levels X1, X2, A2(A), B, C, and D
      are assigned to spin-orbit states arising from low-energy valence configurations
      of BiO with the help of detailed theoretical data calculated by Alekseyev et al.
      (J. Chem. Phys. 100, 8956-8968 (1994)). Copyright 1998 Academic Press.

PMID- 9645927
TI  - The Torsion-Inversion-Bending Energy Levels in the S1(n, pi*) Electronic State of
      Acetaldehyde.
AB  - The band assignments and analyses of the jet-cooled high-resolution laser-induced
      fluorescence excitation spectrum of acetaldehyde that results from the S1(n, pi*)
      electronic state have been extended to +600 cm-1 from the 0(0)0 system origin.
      The new assignments start at Band #7 and finish at Band #21. Bands #8 and #9,
      originally assigned to 14(2)0, have now been assigned to 15(3)0. The assignments
      of the lower energy bands remain unaltered. The origins of the bands that involve
      the torsional modes nu15 (v = 1 to 4) in combination with the wagging mode nu14
      (v = 1 and 2) and the nu10 (v = 1) were determined by analyses with a rigid
      rotational Hamiltonian. These origins were fitted to a set of levels that were
      derived from a torsion-wagging-bending Hamiltonian that employed flexible large
      amplitude coordinates. The resulting potential surface was found to have barriers
      to torsion and inversion of 712.5 and 638.6 cm-1, respectively, with minima in
      the potential hypersurface at theta = 59.9 degrees and alpha = 33.5 degrees for
      the torsion and wagging coordinates. Copyright 1998 Academic Press.

PMID- 9645928
TI  - Sub-Doppler Heterodyne Frequency Measurements on OCS Near 2900 cm-1 Using a CO
      Overtone Sideband Spectrometer.
AB  - We present sub-Doppler heterodyne frequency measurements on 10 rovibrational
      transitions of carbonyl sulfide (OCS) between 2894 and 2910 cm-1. The
      measurements were made using a CO overtone laser which had limited tuneability
      through the generation of microwave sidebands in a CdTe crystal. With this
      technique the laser frequencies were shifted to the desired OCS transition
      frequencies. The transition frequencies could be measured with uncertainties less
      than 30 kHz (Deltanu/nu = 3 x 10(-10)) by frequency offset-locking the CO
      overtone laser to combination frequencies of two saturation-stabilized CO2 laser
      standards. The measured transition frequencies of OCS were combined with previous
      sub-Doppler, Fourier transform, and microwave measurements to recalculate
      improved calibration tables for the 10(0)1-00(0)0, 11(1e)1-01(1e)0, and 11(1f)1
      01(1f)0 bands. These tables are suitable for the calibration of infrared
      spectrometers in the 87 THz region (near 2900 cm-1). Copyright 1998 Academic
      Press.

PMID- 9645929
TI  - The Far-Infrared Spectrum of ClNO2 Studied by High-Resolution Fourier-Transform
      Spectroscopy.
AB  - The far-infrared spectrum of nitryl chloride was studied using high-resolution
      Fourier-transform spectroscopy in the 300-525 cm-1 region. Vibrational band
      centers of fundamental, hot, and difference bands were determined. Furthermore,
      rotational and centrifugal distortion constants up to fourth order for the nu3
      bands of 35ClNO2 and 37ClNO2 (centered at 370 and 364 cm-1, respectively) were
      obtained. The nu5 fundamental of ClNO2 (predicted around 410 cm-1) is very weak
      and overlapped by difference bands. Copyright 1998 Academic Press.

PMID- 9645930
TI  - Tunable Far-Infrared Spectroscopy of 82KrD+, 84KrD+, 86KrD+, and 82KrH+
AB  - Pure rotational spectra of isotopic species of protonated krypton 82KrD+, 84KrD+,
      86KrD+, and 82KrH+ were observed in the 0.75-3.5 THz region, using a tunable far
      infrared radiation source. Rotational parameters B, D, and H of these molecular
      ions were determined. By analyzing the observed frequencies with the previous
      data on all the isotopic species, the mass independent Dunham parameters Ukl,
      DeltaKrkl, and DeltaHkl have been improved. Copyright 1998 Academic Press.

PMID- 9645931
TI  - Faraday Laser Magnetic Resonance Spectroscopy of Vibrationally Excited C2D.
AB  - We studied the gas phase spectrum of the deuterated ethynyl radical C2D in the
      region between 3196 and 3243 cm-1 using a Faraday LMR spectrometer in combination
      with a CO overtone laser. The C2D radicals were generated in a dc glow discharge
      containing helium, deuterium, and acetylene. We observed a hot band between two
      vibronic 2Pi states with an origin at 3225 cm-1. The lower level is assigned to
      the first excited bending level of the electronic X ground state. The upper level
      corresponds to the first excited electronic state A at 3513 cm-1, which was
      observed previously [J. Mol. Struct. 190, 41-60 (1988)]. This region is subject
      to strong vibronic interaction, caused by mixing of the electronic X ground state
      with the A state at 3513 cm-1. From the analysis of the spectra we could
      determine the orbital g factor of the upper level, which gave important
      information about the mixing ratios. In addition we were able to derive a precise
      term value for the first excited bending level of the electronic X ground state.
      The experimentally derived molecular parameters are compared with theoretically
      calculated values, obtained by ab initio calculations. Copyright 1998 Academic
      Press.

PMID- 9645932
TI  - The High-Resolution Infrared Spectrum of the nu5 Band of Deuterated Formic Acid
      (DCOOH).
AB  - The Fourier transform infrared spectrum of the nu5 band of deuterated formic acid
      (DCOOH) has been measured with a resolution of 0.004 cm-1 in the frequency range
      of 1090-1180 cm-1. Using a Watson's A-reduced Hamiltonian in the Ir
      representation, a total of 1731 assigned unperturbed transitions have been
      analyzed to provide rovibrational constants for the upper state (v5 = 1) with a
      standard deviation of 0.000363 cm-1. The band is A type with an unperturbed band
      center at 1142.31075 +/- 0.00002 cm-1. The band is expected to be perturbed by a
      nearby nu4 band through a Fermi resonance term and possibly a Coriolis term. The
      resonance is particularly noticeable for Ka = 10, and 11, at high J values. About
      215 perturbed lines were identified but they were not included in the final fit.
      Copyright 1998 Academic Press.

PMID- 9645933
TI  - Sub-Millimeter-Wave Spectroscopy of the Ar.H+3 and Ar.D+3 Ionic Complexes.
AB  - An investigation of the sub-millimeter-wave spectra of the ionic complexes Ar.H+3
      and Ar.D+3 is presented. These complexes were produced in a negative glow
      electric discharge, in mixtures of argon with either H2 or D2. About 80 new
      transitions were assigned in the 485-680 GHz frequency range using a sub
      millimeter-wave spectrometer built with Russian made backward wave oscillators
      (BWO) sources. These measurements enabled us to observe the first Ka = 2
      transitions for Ar.H+3 and the first Ka = 3 transitions for Ar.D+3. Analyses of
      the line frequencies were carried out using an IAM-like approach, which accounts
      for the large amplitude internal rotation motion displayed by both species.
      Insights into the geometry of the intermediate configuration for this large
      amplitude motion were gained. Copyright 1998 Academic Press.

PMID- 9645934
TI  - Diode Laser Spectroscopy in the 9.8-um nu14 Band of Benzene.
AB  - High-resolution diode laser spectroscopy was applied to measure broadening
      coefficients in the 9.8-um nu14 band of benzene, C6H6. Self-broadening was
      investigated at 295 and 344 K for 73 lines between 1017.31 and 1045.85 cm-1 with
      9 </= J" </= 66 and 1 </= K" </= 66. The measured self-broadening coefficients at
      room temperature vary from 0.12 to 0.22 cm-1/atm (HWHM), whereas at 344 K the
      self-broadening coefficients are in an interval between 0.07 cm-1/atm to 0.16 cm
      1/atm. The Anderson-Tsao-Curnutte (ATC) theory was used to deduce the benzene
      quadrupole moment and the b0 parameter from mean values of the broadening
      coefficients at room temperature. It could be shown that the ATC theory is able
      to describe the quantum number dependence and the absolute values of the self
      broadening coefficients with sufficient accuracy. The collision partner
      dependence of the broadening coefficients was measured for three Q-branch lines
      in benzene mixtures with air, N2, He, Ne, Ar, Kr, and Xe. The results are
      compared with similar experiments with NO2 and SO2 absorption lines with the
      outcome that the qualitative change of the broadening coefficients with changing
      collision partner is similar for all three molecular gases. Air broadening was
      measured for additional five lines at both temperatures mentioned above. The
      experimental setup and the data treatment are described in Part I of this article
      (J. Mol. Spectrosc., 184, 433). Copyright 1998 Academic Press.

PMID- 9645935
TI  - High-Resolution Laser Excitation Spectra of the A2Pi <-- X2Sigma+ System of SrBr:
      The 0-0 and 1-0 Bands of Sr79Br and Sr81Br.
AB  - Two bands (0-0 and 1-0) of the A2Pi-X2Sigma+ system of 88Sr79Br and 88Sr81Br have
      been analyzed rotationally for the first time. Well-resolved spectra were
      recorded by laser excitation spectroscopy with selective detection of
      fluorescence. For each band of the individual isotopomers, about 130 line
      positions with a measurement accuracy of approximately 0.003 cm-1 were employed
      in a least-squares fit of the excited state molecular parameters. The principal
      results for the A2Pi state are Ae = 302.432(1) cm-1 and Re = 2.7147(1) A.
      Copyright 1998 Academic Press.

PMID- 9645936
TI  - Hyperfine Constants and Nuclear Shieldings from the Microwave Spectra of FBO,
      ClBO, and FBS.
AB  - Rotational spectra of the unstable molecules FBO, ClBO, and FBS have been
      measured in the 8-26 GHz frequency range using a pulsed jet cavity Fourier
      transform microwave spectrometer. The samples were prepared by passing electric
      discharges through mixtures of O2/BF3, O2/BCl3, or OCS/BF3, respectively,
      entrained in Ne. Hyperfine structures in the observed transitions have been
      resolved and analyzed in terms of nuclear quadrupole, spin-rotation, and spin
      spin interactions. The quadrupole and spin-rotation coupling constants have been
      used to show that the electronic environment surrounding the boron nucleus of all
      three species is very similar. The spin-rotation constants have been used to
      determine, for the first time, experimental average shieldings of the Cl, F, and
      B nuclei of these molecules. Ab initio values for the nuclear shielding
      parameters have been calculated for comparison. Copyright 1998 Academic Press.

PMID- 9645938
TI  - EDITOR'S NOTE.
AB  - Copyright

PMID- 9645939
TI  - Characterisation of two articulins, the major epiplasmic proteins comprising the
      membrane skeleton of the ciliate Pseudomicrothorax.
AB  - Most protists possess a unique membrane skeleton, the epiplasm, which is involved
      in pattern forming processes of the cell cortex and functions in maintaining cell
      shape. Articulins, a novel class of cytoskeletal proteins, are major constituents
      of the epiplasm. We have isolated cDNAs encoding the two major articulins of the
      ciliate Pseudomicrothorax dubius. Peptide sequence data confirm the identity of
      the cloned cDNAs encoding articulins 1 and 4. With the data presented here
      sequence information for all major articulins of ciliates as well as the
      distantly related euglenoids is available. Sequence comparison of the two newly
      characterised ciliate articulins with the previously determined sequences of p60,
      a minor articulin of the same species, and the two euglenoid articulins reveals
      general sequence principles and uncovers new features of this protein family. The
      hallmark of articulins is a central core domain of repetitive motifs of
      alternating valine and proline residues, the VPV-motif. These VPV-motif repeats
      are either 12-residues, or in some places, six residues long. Positively and
      negatively charged residues segregate in register with valine and proline
      positions. The VPV-motif is unique to articulins. The terminal domains flanking
      the core are generally hydrophobic and contain a series of hexa- or heptapeptide
      repeats rich in glycine and hydrophobic residues. The sequences of these short
      repeats are very similar in articulins of the same species but are not conserved
      between euglenoids and ciliates.

PMID- 9645940
TI  - Chemotaxis of chinese hamster ovary cells expressing the human neutrophil formyl
      peptide receptor: role of signal transduction molecules and alpha5beta1 integrin.
AB  - Activation of the N-formyl peptide receptor (FPR) of human neutrophils by ligands
      such as N-formyl-methionine-leucine-phenylalanine (fMLP) induces mobilization of
      intracellular calcium, cell adhesion, chemotaxis, superoxide production and
      degranulation. Chinese hamster ovary (CHO) cells are normally devoid of FPR and
      unresponsive to fMLP, but when stably transfected with a human FPR cDNA,
      exhibited some of these same responses. Specifically, stimulation with fMLP
      resulted in release of intracellular calcium and chemotactic migration toward a
      gradient of fMLP. As in neutrophils, both processes were inhibited through
      receptor desensitization by prior exposure to a higher or equal concentration of
      ligand or by treatment with pertussis toxin. Soluble and membrane-bound
      fibronectin greatly increased fMLP-induced chemotaxis of CHO cells expressing
      FPR, but not of wild-type CHO cells, suggesting a role for FPR in activation of
      integrin function. Evidence for this hypothesis was obtained by demonstrating
      that CHO cells expressing FPR rapidly increased their adhesion to a fibronectin
      coated surface after stimulation with fMLP. Both chemotaxis and adhesion were
      largely inhibited by RGDS peptide and a function-blocking antibody against alpha5
      integrin. FPR-mediated chemotaxis of the CHO transfectants was partly inhibited
      by a tyrosine kinase inhibitor, herbimycin A, and blocked by a phosphoinositide 3
      kinase inhibitor, wortmannin. These data suggest that stimulation of CHO FPR
      transfectants with a gradient of fMLP results in phosphoinositide 3-kinase
      dependent chemotactic migration, which is enhanced by binding of activated
      alpha5beta1 to fibronectin. This non-myeloid, non-lymphoid fibroblastic cell line
      will thus serve as a useful model to investigate additional requirements of
      signal transduction molecules, adhesion molecules and cytoskeletal elements in
      FPR-mediated chemotaxis.

PMID- 9645941
TI  - Initiation of skin basement membrane formation at the epidermo-dermal interface
      involves assembly of laminins through binding to cell membrane receptors.
AB  - To study the mechanism of basement membrane formation, we determined by
      immunochemistry temporal and spatial expression of laminin-5 (Ln-5), laminin-1
      (Ln-1) and their integrin receptors during early skin morphogenesis. A 3
      dimensional skin culture was used that allows the study of the sequential
      molecular events of basement membrane formation at the epidermodermal interface.
      During early anchorage of keratinocytes to the extracellular matrix there is
      expression of Ln-5, BP-230 antigen and alpha3, beta1 integrin subunits. During
      epidermal stratification and prior to the formation of the lamina densa there is
      assembly of Ln-5, Ln-1, collagen IV and nidogen accompanied by keratinocyte basal
      clustering of alpha2, alpha3, alpha6, beta1, and beta4+ integrin subunits. The
      assembly pattern of Ln-1 and Ln-5 can be disturbed with functional antibodies
      against the beta1 (AIIB2) and alpha6 (GoH3) integrin subunits. Ln-1 assembly can
      also be disturbed with antibodies against its E8 domain and by competitive
      inhibition with a synthetic peptide (AG-73) derived from its G-4 domain.
      Quantitative RT-PCR showed that the dermis contributes about 80% of the laminin
      gamma)1 chain mRNA while 20% is produced by the epidermis which emphasizes its
      dual tissue origin and the major contribution of the mesenchyma in laminin
      production. The laminin gamma2 chain mRNA, present in Ln-5, was mostly of
      epidermal origin. This study presents evidence that during the initiation of
      basement membrane formation, laminins bind to keratinocyte plasma membrane
      receptors and thus may serve as nucleation sites for further polymerization of
      these compounds by a self-assembly process.

PMID- 9645942
TI  - Molecular organization of the desmoglein-plakoglobin complex.
AB  - Different epithelial intercellular junctions contain distinct complexes
      incorporating plakoglobin. In adherens junctions, plakoglobin interacts with two
      molecules, the transmembrane adhesion protein of the cadherin family (e.g. E
      cadherin) and alpha-catenin. The latter is thought to anchor the cadherin
      plakoglobin complex to the cortical actin cytoskeleton. In desmosomes,
      plakoglobin forms a complex with desmosomal cadherins, either desmoglein (Dsg) or
      desmocollin (Dsc), but not with alpha-catenin. To further understand the
      structure and assembly of the plakoglobin-cadherin complexes we analyzed amino
      acid residues involved in plakoglobin-Dsg interactions using alanine scanning
      mutagenesis. Previously, we have shown that plakoglobin interacts with a 72 amino
      acid-long cytoplasmic domain (C-domain) that is conserved among desmosomal and
      classic cadherins. In this paper, we show that a row of the large hydrophobic
      residues located at the C-terminal portion of the Dsg C-domain is indispensable
      for interaction with plakoglobin. To study a reciprocal site we expressed
      plakoglobin (MPg) or its mutants tagged by 6 myc epitope in epithelial A-431
      cells. Using sucrose gradient centrifugation and subsequent co
      immunoprecipitation, MPg was found to be efficiently incorporated into the same
      type of complexes as endogenous plakoglobin. A major pool of Dsg-plakoglobin
      complexes sedimented at 8S and exhibited a 1:1 stoichiometry. Using alanine
      scanning mutagenesis and the co-immunoprecipitation assay we identified nine
      hydrophobic amino acids within the arm repeats 1-3 of plakoglobin, that are
      required for binding to Dsg and Dsc. Eight of these amino acids also participate
      in the interaction with alpha-catenin. No mutations were found to reduce the
      affinity of plakoglobin binding to E-cadherin. These data provide direct evidence
      that the same hydrophobic plakoglobin surface is essential for mutually exclusive
      interaction with distinct proteins such as alpha-catenin and desmosomal
      cadherins.

PMID- 9645943
TI  - A rod end deletion in the intermediate filament protein nestin alters its
      subcellular localization in neuroepithelial cells of transgenic mice.
AB  - Neuroepithelial and radial glial cells span between the ventricular and the pial
      surfaces of the neural tube and express two intermediate filaments (IFs), nestin
      and vimentin, which form a filamentous network throughout the length of the
      cells. In this report we study the polymerization characteristics of nestin and
      examine how mutations affect the assembly and localization of the nestin protein
      in cultured cells and in the developing CNS of transgenic mice. A wild-type rat
      nestin gene transfected into the IF-free SW13 cell line failed to assemble into a
      filamentous network but was incorporated into the existing IF network of a
      subclone expressing vimentin, demonstrating that nestin requires vimentin for
      proper assembly. In transgenic mice, rat nestin formed a network
      indistinguishable from that formed by endogenous nestin and vimentin, but a
      mutant form lacking five amino acids at the carboxy terminus of the rod domain
      was largely restricted to the pial endfeet. Since nestin mRNA is localized to the
      pial endfoot region we propose that both transgenes are translated there, but
      that the wild-type protein is preferentially incorporated into the IF network.
      These observations provide evidence for hierarchical assembly and a complex
      organization of the IF network along the ventricular-pial axis in the early CNS.

PMID- 9645944
TI  - Functional association of nuclear protein 4.1 with pre-mRNA splicing factors.
AB  - Protein 4.1 is a multifunctional polypeptide that links transmembrane proteins
      with the underlying spectrin/actin cytoskeleton. Recent studies have shown that
      protein 4.1 is also present in the nucleus, localized in domains enriched in
      splicing factors. Here we further analyze the relationship between protein 4. 1
      and components of the splicing machinery. Using HeLa nuclear extracts capable of
      supporting the splicing of pre-mRNAs in vitro, we show that anti-4.1 antibodies
      specifically immunoprecipitate pre-mRNA and splicing intermediates.
      Immunodepletion of protein 4.1 from HeLa nuclear extracts results in inhibition
      of their splicing activity, as assayed with two different pre-mRNA substrates.
      Coprecipitation of protein 4.1 from HeLa nuclear extracts with proteins involved
      in the processing of pre-mRNA further suggests an association between nuclear
      protein 4.1 and components of the splicing apparatus. The molecular cloning of a
      4.1 cDNA encoding the isoform designated 4.1E has allowed us to show that this
      protein is targeted to the nucleus, that it associates with the splicing factor
      U2AF35, and that its overexpression induces the redistribution of the splicing
      factor SC35. Based on our combined biochemical and localization results, we
      propose that 4.1 proteins are part of nuclear structures to which splicing
      factors functionally associate, most likely for storage purposes.

PMID- 9645945
TI  - PDGF induces reorganization of vimentin filaments.
AB  - In this study we demonstrate that stimulation with platelet-derived growth factor
      (PDGF) leads to a marked reorganization of the vimentin filaments in porcine
      aortic endothelial (PAE) cells ectopically expressing the PDGF beta-receptor.
      Within 20 minutes after stimulation, the well-spread fine fibrillar vimentin was
      reorganized as the filaments aggregated into a dense coil around the nucleus. The
      solubility of vimentin upon Nonidet-P40-extraction of cells decreased
      considerably after PDGF stimulation, indicating that PDGF caused a redistribution
      of vimentin to a less soluble compartment. In addition, an increased tyrosine
      phosphorylation of vimentin was observed. The redistribution of vimentin was not
      a direct consequence of its tyrosine phosphorylation, since treatment of cells
      with an inhibitor for the cytoplasmic tyrosine kinase Src, attenuated
      phosphorylation but not redistribution of vimentin. These changes in the
      distribution of vimentin occurred in conjunction with reorganization of actin
      filaments. In PAE cells expressing a Y740/751F mutant receptor that is unable to
      bind and activate phosphatidylinositol 3'-kinase (PI3-kinase), the distribution
      of vimentin was virtually unaffected by PDGF stimulation. Thus, PI3-kinase is
      important for vimentin reorganization, in addition to its previously demonstrated
      role in actin reorganization. The small GTPase Rac has previously been shown to
      be involved downstream of PI3-kinase in the reorganization of actin filaments. In
      PAE cells overexpressing dominant negative Rac1 (N17Rac1), no change in the fine
      fibrillar vimentin network was seen after PDGF-BB stimulation, whereas in PAE
      cells overexpressing constitutively active Rac1 (V12Rac1), there was a dramatic
      change in vimentin filament organization independent of PDGF stimulation. These
      data indicate that PDGF causes a reorganization of microfilaments as well as
      intermediate filaments in its target cells and suggest an important role for Rac
      downstream of PI3-kinase in the PDGF stimulated reorganization of both actin and
      vimentin filaments.

PMID- 9645946
TI  - Expression and characterization of splice variants of PYK2, a focal adhesion
      kinase-related protein.
AB  - Focal adhesion kinase and the recently identified proline-rich tyrosine kinase 2
      (PYK2), also known as cell adhesion kinase &bgr ;, related adhesion focal
      tyrosine kinase or calcium-dependent protein tyrosine kinase, define a new family
      of non-receptor protein tyrosine kinases. Activation of PYK2 has been implicated
      in multiple signaling events, including modulation of ion channels, T- and B-cell
      receptor signaling and cell death. Mechanisms underlying the functional diversity
      of PYK2 are unclear. Here, we provide evidence for two novel alternatively
      expressed isoforms of PYK2. One isoform, designated PYK2s (PYK2 splice form),
      appears to be a splice variant of PYK2 lacking 42 amino acids within the C
      terminal domain. A second isoform, referred to as PRNK (PYK2-related non-kinase),
      appears to be specified by mRNAs that encode only part of the C-terminal domain
      of PYK2. Northern blot analysis indicates that the unspliced PYK2 is expressed at
      high levels in the brain and poorly expressed in the spleen, whereas PYK2s and
      PRNK are expressed in the spleen. In situ hybridization studies of rat brain
      demonstrate that the unspliced PYK2 is selectively expressed at high levels in
      hippocampus, cerebral cortex and olfactory bulb, whereas PYK2s and PRNK are
      expressed at low levels in all regions of rat brain examined. Immunofluorescence
      analysis of ectopically expressed PRNK protein shows that PRNK, in contrast to
      full-length PYK2, is localized to focal adhesions by sequences within the focal
      adhesion targeting domain. In addition, PYK2, but not PRNK, interacts with
      p130(cas )and Graf. These results imply that PRNK may selectively regulate PYK2
      function in certain cells by binding to some but not all PYK2 binding partners,
      and the functional diversity mediated by PYK2 may be due in part to complex
      alternative splicing.

PMID- 9645947
TI  - Human colonic cancer cells synthesize and adhere to laminin-5. Their adhesion to
      laminin-5 involves multiple receptors among which is integrin alpha2beta1.
AB  - In the mature gut, laminin-5 is expressed at the basal aspect of the
      differentiating epithelial cells. In vitro, we show that three more or less
      differentiated human colonic cancer HT29 cell lines produce and deposit laminin
      5; they predominantly synthesize and secrete the 440 kDa form of laminin-5 that
      comprises the unprocessed 155 kDa gamma2 chain, as determined by
      immunoprecipitation analysis. In contrast, the highly differentiated colon
      carcinoma Caco-2 cells produce almost no laminin-5. Using anti-integrin
      antibodies, we show that adhesion of the two colonic cancer cell lines to laminin
      5 is mediated by multiple integrin receptors including those for alpha3beta1,
      alpha6beta1 and alpha6beta4 integrins like in other cell types. In addition, the
      implication of integrin alpha2beta1 in this adhesion process is demonstrated for
      the first time. This has been shown by cell adhesion inhibition experiments,
      solid phase assays and confocal analysis. Together with previous in situ
      observations, these data provide a baseline knowledge for the understanding of
      the regulation of laminin-5 in normal and pathological intestine.

PMID- 9645948
TI  - Radial F-actin arrays precede new hypha formation in Saprolegnia: implications
      for establishing polar growth and regulating tip morphogenesis.
AB  - The roles of cortical F-actin in initiating and regulating polarized cell
      expansion in the form of hyphal tip morphogenesis were investigated by analyzing
      long term effects of F-actin disruption by latrunculin B in the oomycete
      Saprolegnia ferax, and detecting localized changes in the cortical F-actin
      organization preceding hyphal formation. Tubular hyphal morphology was dependent
      on proper F-actin organization, since latrunculin induced dose-dependent actin
      disruption and corresponding changes in hyphal morphology and wall deposition.
      With long incubation times (1 to 3 hours), abundant subapical expansion occurred,
      the polar form of which was increasingly lost with increasing actin disruption,
      culminating in diffuse subapical expansion. These extreme effects were
      accompanied by disorganized cytoplasm, and novel reorganization of microtubules,
      characterized by star-burst asters. Upon removing latrunculin, hyperbranching
      produced abundant polar branches with normal F-actin organization throughout the
      colony. The results are consistent with F-actin regulating polar vesicle delivery
      and controlling vesicle fusion at the plasma membrane, and suggest that F-actin
      participates in establishing polar growth. To test this idea further, we utilized
      the hyperbranching growth form of Saprolegnia. Early during the recovery time,
      prior to multiple branch formation, radial arrays of filamentous F-actin were
      observed in regions with no detectable surface protrusion. Their locations were
      consistent with those of the numerous branches that formed with longer recovery
      times. Similar radial arrays preceded germ tube formation in asexual spores. The
      arrays were important for initiating polar growth since the spores lost their
      ability to polarize when the F-actin was disrupted with latrunculin, and
      increased isometrically in size rather than producing germ tubes. Therefore, F
      actin participates in initiating tip formation in addition to its previously
      demonstrated participation in maintenance of hyphal tip growth. The cortical
      location and radial organization of the arrays suggest that they recruit and
      stabilize membrane-bound and cytosolic factors required to build a new tip.

PMID- 9645949
TI  - cyk-1: a C. elegans FH gene required for a late step in embryonic cytokinesis.
AB  - A maternally expressed Caenorhabditis elegans gene called cyk-1 is required for
      polar body extrusion during meiosis and for a late step in cytokinesis during
      embryonic mitosis. Other microfilament- and microtubule-dependent processes
      appear normal in cyk-1 mutant embryos, indicating that cyk-1 regulates a specific
      subset of cytoskeletal functions. Because cytokinesis initiates normally and
      cleavage furrows ingress extensively in cyk-1 mutant embryos, we propose that the
      wild-type cyk-1 gene is required for a late step in cytokinesis. Cleavage furrows
      regress after completion of mitosis in cyk-1 mutants, leaving multiple nuclei in
      a single cell. Positional cloning and sequence analysis of the cyk-1 gene reveal
      that it encodes an FH protein, a newly defined family of proteins that appear to
      interact with the cytoskeleton during cytokinesis and in the regulation of cell
      polarity. Consistent with cyk-1 function being required for a late step in
      embryonic cytokinesis, we show that the CYK-1 protein co-localizes with actin
      microfilaments as a ring at the leading edge of the cleavage furrow, but only
      after extensive furrow ingression. We discuss our findings in the context of
      other studies suggesting that FH genes in yeast and insects function early in
      cytokinesis to assemble a cleavage furrow.

PMID- 9645950
TI  - Interphase-specific association of intrinsic centromere protein CENP-C with
      HDaxx, a death domain-binding protein implicated in Fas-mediated cell death.
AB  - CENP-C, one of the few known intrinsic proteins of the human centromere, is
      thought to play structural as well as regulatory roles crucial to proper
      chromosome segregation and mitotic progression. To further define the functions
      of CENP-C throughout the cell cycle we have used the yeast interaction trap to
      identify proteins with which it interacts. One specific CENP-C interactor, which
      we have named HDaxx, was characterized in detail and found to be homologous to
      murine Daxx, a protein identified through its ability to bind the death domain of
      Fas (CD95). The interaction between CENP-C and HDaxx is mediated by the amino
      terminal 315 amino acids of CENP-C and the carboxyl-terminal 104 amino acids of
      HDaxx. This region of Daxx is responsible for binding to death domains of several
      apoptosis signalling proteins. The biological significance of the interaction
      between CENP-C and HDaxx was confirmed by immunofluorescence colocalization of
      these two proteins at discrete spots in the nuclei of some interphase HeLa cells.
      We discuss the functional implications of the interphase-restricted association
      of HDaxx with centromeres.

PMID- 9645951
TI  - Distinct subcellular localization of calcium binding S100 proteins in human
      smooth muscle cells and their relocation in response to rises in intracellular
      calcium.
AB  - Changes in cytosolic Ca2+ concentration control a wide range of cellular
      responses, and intracellular Ca2+-binding proteins are the key molecules to
      transduce Ca2+ signaling via interactions with different types of target
      proteins. Among these, S100 Ca2+-binding proteins, characterized by a common
      structural motif, the EF-hand, have recently attracted major interest due to
      their cell- and tissue-specific expression pattern and involvement in various
      pathological processes. The aim of our study was to identify the subcellular
      localization of S100 proteins in vascular smooth muscle cell lines derived from
      human aorta and intestinal smooth muscles, and in primary cell cultures derived
      from arterial smooth muscle tissue under normal conditions and after stimulation
      of the intracellular Ca2+ concentration. Confocal laser scanning microscopy was
      used with a specially designed colocalization software. Distinct intracellular
      localization of S100 proteins was observed: S100A6 was present in the
      sarcoplasmic reticulum as well as in the cell nucleus. S100A1 and S100A4 were
      found predominantly in the cytosol where they were strongly associated with the
      sarcoplasmic reticulum and with actin stress fibers. In contrast, S100A2 was
      located primarily in the cell nucleus. Using a sedimentation assay and subsequent
      electron microscopy after negative staining, we demonstrated that S100A1 directly
      interacts with filamentous actin in a Ca2+-dependent manner. After thapsigargin
      (1 microM) induced increase of the intracellular Ca2+ concentration, specific
      vesicular structures in the sarcoplasmic reticulum region of the cell were formed
      with high S100 protein content. In conclusion, we demonstrated a distinct
      subcellular localization pattern of S100 proteins and their interaction with
      actin filaments and the sarcoplasmic reticulum in human smooth muscle cells. The
      specific translocation of S100 proteins after intracellular Ca2+ increase
      supports the hypothesis that S100 proteins exert several important functions in
      the regulation of Ca2+ homeostasis in smooth muscle cells.

PMID- 9645952
TI  - Vesicle-associated brain myosin-V can be activated to catalyze actin-based
      transport.
AB  - Myosin-V has been linked to actin-based organelle transport by a variety of
      genetic, biochemical and localization studies. However, it has yet to be
      determined whether myosin-V functions as an organelle motor. To further
      investigate this possibility, we conducted a biochemical and functional analysis
      of organelle-associated brain myosin-V. Using the initial fractionation steps of
      an established protocol for the purification of brain myosin-V, we isolated a
      population of brain microsomes that is approx. fivefold enriched for myosin-V,
      and is similarly enriched for synaptic vesicle proteins. As demonstrated by
      immunoelectron microscopy, myosin-V associates with 30-40% of the vesicles in
      this population. Although a majority of myosin-V-associated vesicles also label
      with the synaptic vesicle marker protein, SV2, less than half of the total SV2
      positive vesicles label with myosin-V. The average size of myosin-V/SV2 double
      labeled vesicles (90+/-45 nm) is larger than vesicles that label only with SV2
      antibodies (60+/-30 nm). To determine if these vesicles are capable of actin
      based transport, we used an in vitro actin filament motility assay in which
      vesicles were adsorbed to motility assay substrates. As isolated, the myosin-V
      associated vesicle fraction was nonmotile. However, vesicles pre-treated with ice
      cold 0.1% Triton X-100 supported actin filament motility at rates comparable to
      those on purified myosin-V. This dilute detergent treatment did not disrupt
      vesicle integrity. Furthermore, while this treatment removed over 80% of the
      total vesicle proteins, myosin-V remained tightly vesicle-associated. Finally,
      function-blocking antibodies against the myosin-V motor domain completely
      inhibited motility on these substrates. These studies provide direct evidence
      that vesicle-associated myosin-V is capable of actin transport, and suggest that
      the activity of myosin-V may be regulated by proteins or lipids on the vesicle
      surface.

PMID- 9645953
TI  - Compressive force promotes sox9, type II collagen and aggrecan and inhibits IL
      1beta expression resulting in chondrogenesis in mouse embryonic limb bud
      mesenchymal cells.
AB  - The initial modeling and subsequent development of the skeleton is controlled by
      complex gene-environment interactions. Biomechanical forces may be one of the
      major epigenetic factors that determine the form and differentiation of skeletal
      tissues. In order to test the hypothesis that static compressive forces are
      transduced into molecular signals during early chondrogenesis, we have developed
      a unique three-dimensional collagen gel cell culture system which is permissive
      for the proliferation and differentiation of chondrocytes. Mouse embryonic day 10
      (E10) limb buds were microdissected and dissociated into cells which were then
      cultured within a collagen gel matrix and maintained for up to 10 days. Static
      compressive forces were exerted onto these cultures. The time course for
      expression pattern and level for cartilage specific markers, type II collagen and
      aggrecan, and regulators of chondrogenesis, Sox9 and IL-1beta, were analyzed and
      compared with non-compressed control cultures. Under compressive conditions,
      histological evaluation showed an apparent acceleration in the rate and extent of
      chondrogenesis. Quantitatively, there was a significant 2- to 3-fold increase in
      type II collagen and aggrecan expression beginning at day 5 of culture and the
      difference was maintained through 10 days of cultures. Compressive force also
      causes an elevated level of Sox9, a transcriptional activator of type II
      collagen. In contrast, the expression and accumulation of IL-1beta, a
      transcriptional repressor of type II collagen was down-regulated. We conclude
      that static compressive forces promote chondrogenesis in embryonic limb bud
      mesenchyme, and propose that the signal transduction from a biomechanical stimuli
      can be mediated by a combination of positive and negative effectors of cartilage
      specific extracellular matrix macromolecules.

PMID- 9645954
TI  - Proopiomelanocortin (POMC) mRNA expression: distribution and region-specific down
      regulation by chronic morphine in female guinea pig hypothalamus.
AB  - There is compelling evidence that endogenous opioid peptides are regulated by
      exogenous opiates. Our previous studies have shown that the mu-opioid receptor
      protein and mRNA are down-regulated in the mediobasal hypothalamus of the female
      guinea pig following chronic morphine treatment. In addition,
      electrophysiological studies have shown that hypothalamic beta-endorphin (beta
      EP) neurons express mu-opioid receptors that are uncoupled and down-regulated
      following chronic morphine treatment. Currently, we tested the hypothesis that
      chronic morphine, which produces down-regulation of mu-opioid receptors, causes a
      down-regulation of pro-opiomelanocortin (POMC, the precursor of beta-EP) mRNA
      expression in female guinea pig hypothalamus. Female guinea pigs were
      ovariectomized and implanted subcutaneously (s.c.) with 4 x 75 mg pellets for 2
      days plus six more pellets of either morphine (n = 6) or placebo (n = 6) for
      another 5 days. Animals were sacrificed between 1000 and 1100 h on day 7. The
      expression of POMC mRNA were investigated using in situ hybridization
      histochemistry with a guinea pig specific 35S-labeled cRNA probe in hypothalamic
      tissue sections. POMC mRNA was localized to the arcuate nucleus (Arc) and median
      eminence (ME) of the medial basal hypothalamus. The distribution pattern was the
      same in both morphine and placebo control animals. However, the density of silver
      grains was less in morphine treated animals versus placebo control animals.
      Overall, the level of POMC mRNA was decreased by 22% in the Arc of morphine
      treated guinea pigs as compared with the placebo controls (p < 0.05). This
      decrease in POMC mRNA expression was even greater in the caudal Arc (28%, p <
      0.01) in morphine-treated animals. These results suggested that the biosynthetic
      activity of POMC neurons is down-regulated with chronic exposure to morphine.

PMID- 9645955
TI  - Temporal changes in gene expression following cryogenic rat brain injury.
AB  - Expression of 18 genes was examined at 8 different time points between 1 h and 28
      days following cryogenic rat brain injury. The genes include thymidine kinase
      (TK), p53 tumor suppressor, c-fos, renin, myelin basic protein (MBP), proteolipid
      protein (PLP), transferrin, transferrin receptor, platelet-derived growth factor
      A (PDGF A), platelet-derived growth factor B (PDGF B), platelet-derived growth
      factor receptor alpha (PDGF alpha receptor), platelet-derived growth factor
      receptor beta (PDGF beta receptor), glial fibrillary acidic protein (GFAP),
      transforming growth factor-beta 1 (TGF-beta 1), basic fibroblast growth factor
      (bFGF), fibroblast growth factor receptor-1 (FGF-R1), insulin-like growth factor
      1 (IGF-1), and somatostatin. Time courses of gene expression were determined for
      RNAs derived from hippocampus and cortex. Genes were divided into categories
      based upon those in which statistically significant changes in expression were
      first observed at or before 24 h (early genes) and those in which changes were
      first observed at or after 72 h (late genes). In the present model, many genes
      demonstrate elevated RNA levels in the cortex prior to hippocampus, following
      injury. RNAs transcribed from late genes tend to be elevated concurrently in
      cortex and hippocampus.

PMID- 9645956
TI  - BDNF acutely increases tyrosine phosphorylation of the NMDA receptor subunit 2B
      in cortical and hippocampal postsynaptic densities.
AB  - While neurotrophins are critical for neuronal survival and differentiation,
      recent work suggests that they acutely regulate synaptic transmission as well.
      Brain-derived neurotrophic factor (BDNF) enhances excitatory postsynaptic
      currents in cultured dissociated hippocampal neurons within 2-3 min through
      postsynaptic, phosphorylation-dependent mechanisms. Moreover, BDNF modulates
      hippocampal long-term potentiation, in which postsynaptic NMDA (N-methyl-D
      aspartate) receptors (NRs) play a key role. We now report that BDNF acutely
      increases tyrosine phosphorylation of the specific NMDA receptor subunit NR2B,
      which has recently been shown to play a role in long-term potentiation.
      Incubation of BDNF with cortical or hippocampal postsynaptic densities for 5 min
      increased tyrosine phosphorylation of the NR2B subunits in a dose-dependent
      manner. A maximal increase to 165% of control phosphorylation occurred at a BDNF
      concentration of 2 ng/ml. The BDNF action appeared to be specific, since nerve
      growth factor, another member of the neurotrophin gene family, had no effect on
      NR2B phosphorylation. Further, BDNF action was selective, since it did not alter
      tyrosine phosphorylation of NR2A subunits. Our results suggest that tyrosine
      phosphorylation of NR2B subunits of the NMDA receptor may contribute to
      neurotrophin modulation of postsynaptic responsiveness and long-term
      potentiation.

PMID- 9645957
TI  - Granule cell development in the cerebellum is punctuated by changes in Sox gene
      expression.
AB  - Development of the vertebrate cerebellum is unusual compared to most other
      regions of the brain since it involves two germinal regions. Most cell types
      arise from the luminal, ventricular zone as in other brain regions, but granule
      cells arise from the second germinal layer, the external granular layer (EGL).
      Our analysis of the temporal and positional expression of three members of the
      Sox gene family of transcription factors in the cerebellum shows that granule
      cell development is unusual compared to most other neurons of the central nervous
      system (CNS). We show that granule cell precursors lose expression of cSox2 and
      cSox3 as they migrate to form the EGL. The EGL is the first example of a germinal
      layer in the CNS which does not exhibit expression of these genes. Throughout
      most of the CNS cSox11 expression is very low in the ventricular zone but
      increases dramatically as cells cease proliferation and migrate to form the
      subventricular zone. We also find that cSox11 expression increases when cells of
      the cerebellum migrate to form the EGL, but levels of expression as high as that
      in the subventricular zone are only seen when cells cease proliferation and
      migrate inwards to form the deep EGL. These observations demonstrate that cells
      of the proliferative superficial EGL differ qualitatively from cells of the
      ventricular zone in their expression of Sox genes whereas the post-proliferative
      cells of the deep EGL appear analogous, in their expression of Sox genes, to
      cells of the subventricular zone.

PMID- 9645958
TI  - Enhancement of beta-amyloid precursor protein transcription and expression by the
      soluble interleukin-6 receptor/interleukin-6 complex.
AB  - We investigated a potential role for the soluble interleukin-6 receptor (sIL-6R)
      in modulating interleukin-6 (IL-6) function in the central nervous system by
      assessing IL-6 and sIL-6R effects on beta-amyloid precursor protein (beta-APP)
      transcription and expression in cells of human neuronal origin. Cells transfected
      with a luciferase reporter plasmid containing a 3.8 kb DNA fragment of the beta
      APP promoter were shown to have inducible promoter activity when treated with
      phorbol ester or basic fibroblast growth factor, but not when treated with
      lipopolysaccharide or Il-6. PCR amplification analysis revealed the presence of
      mRNA encoding the signaling subunit of the Il-6 receptor complex, the gp130
      subunit, at levels approximating that found in human cortical tissue. The mRNA
      encoding the IL-6 receptor, however, was poorly expressed and was detectable only
      at high amplification cycles. When purified sIL-6R protein was added together
      with IL-6, there was a rapid induction of promoter activity within 2 h of
      stimulation followed by elevations in protein levels of both cell-associated and
      secreted beta-APP. Analysis of mRNA transcripts from human cortical brain tissue
      and cell cultures derived from fetal human brain demonstrated the presence of an
      alternatively spliced secreted form of the IL-6 receptor mRNA, suggesting that
      cells of the central nervous system may themselves be a source of sIL-6R protein.
      The capacity for sIL-6R to enhance IL-6 function and broaden the IL-6 target cell
      population in the brain has implications for the regulation of beta-APP
      expression in disease states such as Alzheimer's disease where elevations in
      brain IL-6 levels have been reported.

PMID- 9645959
TI  - Complex expression pattern of the SCO-spondin gene in the bovine subcommissural
      organ: toward an explanation for Reissner's fiber complexity?
AB  - Bovine SCO-spondin is a glycoprotein secreted by the subcommissural organ (SCO),
      an ependymal derivative located in the roof of the third ventricle. It shows
      homology with developmental molecules involved in directional axonal growth.
      Using SCO-spondin cDNAs as probes, we analysed the specific expression of the
      corresponding gene in the bovine SCO by Northern blot and in situ hybridization
      (ISH). A strong expression was detected in the secretory ependymal and hypendymal
      cells of the SCO and the main transcripts showed a large size 14 kb. A single
      copy gene was revealed by Southern blot analysis of bovine genomic DNA. The
      presence of additional transcripts suggested a transcriptional regulation of the
      SCO-spondin gene. A comparative analysis of the results obtained by molecular and
      immunological techniques (immunoblotting and immunopurification) pointed to the
      presence of several SCO-spondin related proteins in the SCO encoded by the same
      gene. The presence in the cerebral hemispheres (CH) of a 54-kDa glycoprotein with
      a common epitope is discussed as a putative cleaved SCO-spondin product carried
      by the cerebrospinal fluid, that may act on neuronal development.

PMID- 9645960
TI  - Increased transcription of glutamate-aspartate transporter (GLAST/GluT-1) mRNA
      following kainic acid-induced limbic seizure.
AB  - Expression of mRNA for glutamate-aspartate transporter (GLAST/GluT-1/EAAT1) was
      studied in the brain of the rat which presented recurrent limbic seizure
      following systemic administration of kainic acid (KA) by in situ hybridization
      and Northern blot analysis. The expression of GLAST mRNA was markedly increased
      after 12 h and peaked after 48 h in animals which demonstrated limbic seizure.
      The induction of the mRNA were observed in the small non-neuronal cells in the
      hippocampus, especially around CA3 region and hilus. In contrast, there was no
      change in GLAST mRNA levels in KA injected seizure-free animals. These findings
      suggest that GLAST mRNA is induced by seizure and increased extracellular
      glutamate levels during seizure may be important for induction of GLAST mRNA.

PMID- 9645961
TI  - CBF/NF-Y activates transcription of the human tryptophan hydroxylase gene through
      an inverted CCAAT box.
AB  - The human tryptophan hydroxylase gene (hTPH) encodes the rate-limiting enzyme in
      the biosynthesis of serotonin, a neurotransmitter which has been implicated in a
      number of psychiatric illnesses. This enzyme is expressed in a tissue-specific
      manner. We examined the transcriptional activity of a series of 5' deletion
      promoter-reporter constructs extending from nucleotide (nt) -1954 to +40 and
      found that the region between nt -163 and +40 contains a regulatory element
      important for efficient transcription of the gene, DNase I footprint analyses,
      using P815-HTR and HeLa nuclear protein extracts, revealed a single prominent
      footprint between nt -78 and -44. A cis-acting element in the footprint region
      was identified as an inverted CCAAT box (-67 ATTGG -63) by gel shift assays. Two
      base pair (bp) mutations in the core CCAAT sequence eliminated protein binding in
      gel shift assays and reduced transcriptional activity approximately 50% in
      transient transfection assays. Competitive gel shift assays showed that the
      protein binding to the hTPH CCAAT box was effectively competed by an
      oligonucleotide (oligo) harboring a binding site for CCAAT box binding factor
      (CBF)/nuclear factor-Y (NF-Y). A selective antibody against the B subunit of
      CBF/NF-Y supershifted the protein-DNA complex formed between the -90/-50 oligo
      probe and nuclear protein extracts. Our results indicate that the binding of
      CBF/NF-Y to the inverted CCAAT box is responsible for transcriptional activation
      of the nTPH gene.

PMID- 9645962
TI  - Differential regulation of ciliary neurotrophic factor (CNTF) and CNTF receptor
      alpha (CNTFR alpha) expression following focal cerebral ischemia.
AB  - Ciliary neurotrophic factor (CNTF) is a member of cytokines, with trophic effects
      on ciliary, motor sympathetic, sensory, retinal and hippocampal neurons. In the
      present study, we examined the temporal and spatial expression profiles of CNTF
      and CNTF receptor alpha (CNTFR alpha) mRNAs in a focal cerebral ischemia model
      induced by transient occlusion of the right middle cerebral artery and both
      common carotid arteries. Northern blot analysis showed a slow and sustained
      increase in the 1.2 kb transcript of CNTF mRNA in the ischemic cortex of rats
      subjected to a transient 60 min ischemic insult. A delayed decrease in the 2.1 kb
      transcript of CNTFR alpha mRNA in the ischemic cortex was observed in rats
      subjected to 60 min ischemia followed by 72 h of reperfusion. In situ
      hybridization studies revealed constitutive expression of CNTFR alpha mRNA in the
      majority of neurons in the brain. Following 4 h of reperfusion, increased
      expression of CNTFR alpha mRNA was observed in the ipsilateral dentate gyrus,
      which is opposite to the down-regulation noted in the ischemic cortex. Within the
      infarct area CNTFR alpha mRNA had a marked increase in cortical layer II but a
      decrease in cortical layer V following 1 day of reperfusion. No signal of CNTFR
      alpha mRNA was detected within the infarct region following 3 days of
      reperfusion. Following 1 week of reperfusion, although no marked changes was
      observed in the level of CNTFR alpha mRNA in the area immediately surrounding the
      necrosis region where the reactive astrocytes were noted, a striking increase in
      the CNTF mRNA signal was noted. In summary, differential regulation of CNTF and
      CNTFR alpha mRNAs was noted in the ischemic cortex. Regional differences in CNTF
      receptor expression were noted between the ischemic cortex and ipsilateral
      dentate gyrus as well as between cortical layer II and V within the infarct
      region. CNTF mRNA, but not CNTFR alpha mRNA, had a marked increase in the area
      immediately adjacent to the necrosis. The mechanisms and patho-physiological
      significance for these differential regulation remain to be studied.

PMID- 9645963
TI  - Transcript-specific effects of adrenalectomy on seizure-induced BDNF expression
      in rat hippocampus.
AB  - Activity-induced brain-derived neurotrophic factor (BDNF) expression is
      negatively modulated by circulating adrenal steroids. The rat BDNF gene gives
      rise to four major transcript forms that each contain a unique 5' exon (I-IV) and
      a common 3' exon (V) that codes for BDNF protein. Exon-specific in situ
      hybridization was used to determine if adrenalectomy has differential effects on
      basal and activity-induced BDNF transcript expression in hippocampus.
      Adrenalectomy alone had only modest effects on BDNF mRNA levels with slight
      increases in exon III-containing mRNA with 7-10-day survival and in exon II
      containing mRNA with 30-days survival. In the dentate gyrus granule cells,
      adrenalectomy markedly potentiated increases in exon I and II cRNA labeling, but
      not increases in exon III and IV cRNA labeling, elicited by one hippocampal
      afterdischarge. Similarly, for the granule cells and CA1 pyramidal cells, hilus
      lesion (HL)-induced recurrent limbic seizures elicited greater increases in exon
      I and II cRNA hybridization in adrenalectomized (ADX) as compared to adrenal
      intact rats. In this paradigm, adrenalectomy modestly potentiated the increase in
      exon III-containing mRNA in CA1 but had no effect on exon IV-containing mRNA
      content. These results demonstrate that the negative effects of adrenal hormones
      on activity-induced BDNF expression are by far the greatest for transcripts
      containing exons I and II. Together with evidence for region-specific transcript
      expression, these results suggest that the effects of stress on adaptive changes
      in BDNF signalling will be greatest for neurons that predominantly express
      transcripts I and II.

PMID- 9645964
TI  - Regulation of the sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) 2 gene
      transcript in neuronal cells.
AB  - The sarco/endoplasmic reticulum Ca(2+)-transport ATPase (SERCA2) pre-mRNA is
      alternatively processed in a tissue-specific manner. At its 3' end, two 5' splice
      donor sites compete for the same 3' acceptor splice site (3'A). While the
      upstream 5' donor splice site (5'D1) is used in muscle cells giving rise to the
      class 1 mRNA, the downstream one (5'D2) is exclusively used in neuronal cells
      generating the class 4 mRNA. Using a neuroblastoma cell line and a minigene
      containing the 3' end of the SERCA2 gene, we have investigated the regulation of
      the neuronal-type of splicing. We have shown that a strong 3'A is required for
      splicing because exchanging it for a weaker one abolishes splicing. A second
      region spanning the entire exon 25 downstream of the 3'A is also necessary for
      the repression of the muscle-specific splicing in neuronal cells. In addition the
      tissue-specific (muscle/neuron) selection of the appropriate 5' donor splice site
      seems to be determined by at least two distinct but adjacent negative cis-active
      elements located in the last 237 nt of the optional exon 24. The upstream
      negative element controls the neuronal splicing while the downstream one
      represses the muscle-specific splicing in neuronal cells. It is suggested that
      the cis-active elements in the gene transcript are the target of trans-acting
      factors that are responsible for the repression of neuronal- or muscle-specific
      splicing in a tissue-specific manner.

PMID- 9645965
TI  - AP-1, CREB and CBP transcription factors differentially regulate the tyrosine
      hydroxylase gene.
AB  - The tyrosine hydroxylase (TH) gene encodes the rate-limiting enzyme in the
      biosynthesis of catecholamines. We have investigated the roles of two elements of
      the TH promoter, the TH-'Fat Specific Element' (TH-FSE) which binds the Fos-Jun
      complex, and the cAMP Response Element (CRE), which binds CREB and the co
      activator protein, CREB Binding Protein (CBP) in regulating TH gene
      transcription. In PC12 cells, the TH-FSE was required for induction by NGF while
      the CRE was required for induction by cAMP. We show that both elements can
      function independently and contribute strongly to TH promoter basal activity in
      PC12 cells. We employed transient expression in the F9 teratocarcinoma cell line
      to vary experimentally the levels of the nuclear regulators implicated in TH
      control by the PC12 studies. In F9 cells, the TH promoter was strongly activated
      by Fos and Jun, and by PKA-stimulated CREB protein. In F9 and NIH3T3 cells, CBP,
      a co-activator which targets Fos-Jun and PKA-stimulated CREB, also induced the TH
      promoter. Immunohistochemical studies in rat brain regions enriched in
      dopaminergic neurons, including the midbrain and olfactory bulb (OB), suggest
      that Fos-Jun and CREB make differential contributions to TH gene activity in
      different tissues. Whereas changes in Fos protein levels parallel decreases in TH
      protein upon olfactory deprivation, CBP levels remain unchanged. This suggests
      that CRE-associated factors, including CBP, are not major regulators in the OB.
      In contrast, the presence of CREB and the absence of Fos immunoreactivity in
      midbrain dopaminergic cells suggests that the CRE is the primary regulator in
      this region.

PMID- 9645967
TI  - Chronic administration of cannabinoids regulates proenkephalin mRNA levels in
      selected regions of the rat brain.
AB  - This study was designed to examine the interactions between the cannabinoid and
      enkephalinergic systems in the rat brain. To this aim, we have examined the
      effects of subchronic (5 days) administration (10 mg.kg-1.day-1; i.p.) of delta 9
      -tetrahydrocannabinol (THC) or R-methanandamide (AM356) and chronic (18 days)
      administration with the synthetic cannabinoid receptor agonist CP-55,940 (1 mg.kg
      1.day-1; i.p) on proenkephalin (PENK) mRNA levels in several brain regions of the
      rat. Twenty micrometer brain sections from striatum, nucleus accumbens,
      paraventricular nucleus, ventromedial nucleus, periaqueductal grey matter and
      mammillary nucleus were hybridized with an oligonucleotide probe complementary to
      PENK using in situ hybridization technique. Subchronic administration of THC or
      AM356 increased PENK mRNA levels in the ventromedial nucleus of the hypothalamus,
      (82%) and (39%), in the periaqueductal grey matter, (97%) and (49%), and
      mammillary nucleus, (43%) and (9%), respectively. In contrast, both drugs were
      without effect in the striatum and nucleus accumbens. On the other hand, chronic
      administration of CP-55,940 increased PENK mRNA levels in the striatum (44%),
      nucleus accumbens (25%), paraventricular (31%) and ventromedial nuclei of the
      hypothalamus (41%). These results revealed that chronic cannabinoid
      administration increases opioid gene expression in the rat central nervous system
      and suggest an interaction between the cannabinoid and enkephalinergic systems
      that may be part of a molecular integrative response to behavioral and
      neurochemical alterations that occur in cannabinoid drug abuse.

PMID- 9645966
TI  - Differential regulation of AP-1 DNA binding activity in rat hypothalamus and
      pituitary by estrogen.
AB  - Ap-1 proteins such as Fos and Jun are nuclear transcription factors that have
      been postulated to function as third messengers in signal transduction pathways
      to regulate target gene expression. Using electrophoretic mobility shift assays
      (EMSA), we have studied estrogen (E) effects on regulation of AP-1 DNA binding
      activity in the rat hypothalamus and pituitary. AP-1 binding is defined herein as
      the specific association with a consensus AP-1 site during EMSA. Specific AP-1
      binding activity was observed in nuclear extracts from the hypothalamus and
      pituitary of ovariectomized (OVX) female and castrated (CAS) male rats. Treatment
      with E increased the levels of AP-1 binding activity in the pituitary and uterus,
      whereas E decreased the levels of AP-1 binding in the hypothalamus, of OVX
      females. These effects were observed within 60 min and maintained for at least 72
      h after a single dose of estrogen. Estrogen-induced changes in AP-1 binding were
      much more prominent in OVX females than in CAS males. Treatment with progesterone
      in OVX females had no significant effects on AP-1 binding activity in either
      pituitary or hypothalamus. Analysis of AP-1 binding activity in both hypothalamus
      and pituitary by supershift, immunodepletion and shift-Western blot indicated
      that part of the AP-1 binding was due to the presence of Fos and Jun proteins.
      However, Western blot analysis shows that the levels of Fos and Jun proteins in
      the hypothalamic nuclear extracts were not altered by E treatment. We conclude
      that E produced tissue and sex-differentiated alterations in AP-1 DNA binding
      activity in the hypothalamus and pituitary of female rats, which may be related
      to differential estrogenic actions on gene regulation.

PMID- 9645968
TI  - Reduction of cortical infarction and impairment of apoptosis in NGF-transgenic
      mice subjected to permanent focal ischemia.
AB  - The neuroprotective potential of the nerve growth factor (NGF) against permanent
      ischemic brain damage has been investigated in vivo using NGF-transgenic (tg)
      mice. The expression of the transgene is driven by part of the promoter of the
      proto-oncogene c-fos, which belongs to the first set of genes activated after
      brain ischemic insult. Wild-type (wt) mice and tg mice were subjected to
      permanent focal ischemia induced by electrocoagulation of the middle cerebral
      artery. Twenty four hours (h) after the ischemic shock, when compared to wt, tg
      mice displayed a 40% reduction of the infarcted area, which lasted up to 1 week.
      However, infarcted brain areas were similar in wt and tg mice within the first
      hours post-occlusion, indicating that NGF acted to block the progression of
      neuronal damage. Kinetics of NGF synthesis assessed by ELISA was in good
      agreement with the observed neuroprotective effect, since NGF content peaked 6 h
      post-ischemia. This was further correlated with the time-course of c-Fos
      immunoreactivity, detectable only from 6 h post-ischemia. The neuroprotective
      effect of NGF involved the impairment of apoptotic cell death, as evidenced by a
      marked decrease of the number of apoptotic profiles inside the ischemic zone in
      tg mice. These results underline the potential of c-fos-NGF-tg mice to study in
      vivo the molecular and cellular mechanisms of the NGF-induced neuroprotective
      effect against ischemic damage.

PMID- 9645969
TI  - Regulation of kappa-opioid receptor mRNA level by cyclic AMP and growth factors
      in cultured rat glial cells.
AB  - The mRNA of the kappa-opioid receptor (KOR) has been found recently in cultured
      astrocytes and in microglia. By using RT-PCR and Southern hybridization, we
      confirmed these observations and, in addition, we observed that KOR mRNA was
      expressed in oligodendrocytes and in the precursors of astrocytes and
      oligodendrocytes. KOR mRNA level was the highest in the immature astrocytes and
      decreased with their maturation. Very few data are available on the regulation of
      KOR level by extracellular signals. Therefore, we examined the effect of three
      growth factors known to be present in the adult brain, basic fibroblast growth
      factor (bFGF), platelet-derived growth factor (PDGF-BB) and leukemia inhibitory
      factor (LIF) and of two cyclic AMP (cAMP) generating systems, the cAMP analog, 8
      (4-chlorophenylthio)-cAMP and forskolin, on this level. It was found that in
      astrocytes, KOR mRNA level decreased dramatically under the effect of cAMP and
      less under the effect of bFGF while it did not change significantly after LIF
      treatment. In oligodendrocytes, it also decreased with cAMP, but increased under
      the effect of bFGF and PDGF-BB. In microglia, a decrease was observed with cAMP
      and lipopolysaccharides (LPS), the most used activators of macrophages. These
      results shed new evidence on the expression of opioid receptor mRNA in the glial
      cells of the rat CNS. The regulation of KOR mRNA level under the effect of
      extracellular signals suggests that opioids take part in dynamic processes in
      glial cells, possibly related to glial-neuron communication.

PMID- 9645970
TI  - Antisense oligonucleotides to the GluR2 AMPA receptor subunit modify excitatory
      synaptic transmission in vivo.
AB  - In the brain, fast wxcitatory synaptic transmission is mostly mediated by the
      alpha-amino-3-hydroxy-5-methyl-isoxazole-propionic acid (AMPA) subtype of the
      glutamate receptors. Molecular cloning has revealed that four subunits, GluR1,
      GluR2, GluR3, and GluR4 form heteromeric receptors with high affinity for AMPA.
      Because antagonists and agonists do not discriminate between individual AMPA
      receptor subunits, we decided to use antisense oligonucleotides to block the
      expression of the GluR2 subunit within the receptor complex in adult animals. In
      the present study, we exploited several advantages afforded by the guinea pig
      cochlea to determine whether an antisense oligonucleotide directed to the mRNA of
      the GluR2 subunit could modify primary auditory neurotransmission. While a random
      probe with the same base composition had no effect, a GluR2 antisense
      oligonucleotide, continuously delivered into the cochlea, transiently reduced the
      compound action potential and diminished spontaneous activity of single auditory
      nerve fibers. Although antisense oligonucleotides penetrated a variety of cells,
      their effect could be physiologically localized to a single site of GluR2
      antisense probe action, the primary auditory neuron. Subunit specificity of this
      effect was confirmed by a significant reduction in GluR2/3, but not GluR4
      immunoreactivity in primary auditory neurons. Besides being the first
      demonstration that transient knockout of GluR2 subunit in adult animal modifies
      excitatory synaptic transmission in vivo, these results support the use of the
      antisense strategy as a powerful tool for blocking expression of any gene in the
      cochlea.

PMID- 9645971
TI  - RT-PCR analysis of mRNA expression of natriuretic peptide family and their
      receptors in rat inner ear.
AB  - To assess the possible physiological role of the atrial natriuretic peptide (ANP)
      family, we investigated the expression of mRNA of ANP, brain natriuretic peptide
      (BNP), C-type natriuretic peptide (CNP), and their receptors in rat inner ear
      using the reverse transcription-polymerase chain reaction method. ANP and CNP
      message bands were detected in the inner ear, but the BNP message band was not.
      Amplification products of the expected sizes of ANP-A, ANP-B and ANP-C receptors
      were detected in the inner ear. These results suggest that natriuretic peptide
      family may influence the function of the inner ear through the ANP-A, ANP-B, and
      ANP-C receptors.

PMID- 9645972
TI  - Acute 17 beta-estradiol treatment down-regulates serotonin 5HT1A receptor mRNA
      expression in the limbic system of female rats.
AB  - In situ hybridization histochemistry was used to investigate acute estrogen
      effects on serotonin 5HT1A receptor mRNA levels in limbic-related brain areas in
      the female ovariectomized rat. Acute administration of 17 beta-estradiol (10
      micrograms) decreased 5HT1A receptor mRNA expression levels within the medial
      amygdala (after 2 and 24 h), piriform cortex (after 2 and 24 h), and perirhinal
      cortex (after 24 h). No changes in 5HT1A mRNA levels were observed in hippocampus
      or retrosplenial cortex. The findings suggest specific regional effects of
      estrogen on 5HT functions mediated through regulation of the 5HT1A gene.

PMID- 9645973
TI  - Isolation and characterization of a leech neuropeptide in rat brains: coupling to
      nitric oxide release in leech, rat and human tissues.
AB  - The osmoregulator peptide (leech osmoregulatory factor, LORF; IPEPYVWD) was first
      found in the leech central nervous system (CNS). Given the fact that certain
      peptides can be found in mammals and invertebrates, e.g., opioid, we examined rat
      brains to determine if LORF was present. This peptide was found and isolated by
      successive reversed-phase HPLC purification steps and characterized by
      electrospray mass spectrometry measurement. It was sequenced by Edman degradation
      and quantified in different tissues by ELISA. Our results demonstrate the
      presence of LORF in the hypothalamus, thalamus, and striatum (6 pmol/mg of
      protein extract) and in other brain areas at lower levels. This octapeptide is
      also present in the rat duodenum and liver (10 to 14 pmol/mg) and at lower levels
      in heart, lung, pancreas and caudal spinal cord (< 5 pmol/mg). The testes,
      adrenals and kidneys have the lowest levels of all the tissues examined (ca. 0.5
      pmol/mg of protein). Furthermore, we also demonstrate that LORF is coupled to
      nitric oxide (NO) release in leech CNS, rat hypothalamus and human saphenous vein
      in a manner which is inhibited by a nitric oxide synthase inhibitor as well as an
      antibody directed toward LORF. The study demonstrates that LORF, and its function
      in relation to NO release, has been conserved over more than 400 million years of
      evolution.

PMID- 9645974
TI  - Cerebral cysticercotic arteritis: detection and follow-up by transcranial
      Doppler.
AB  - Intracranial arteritis is a well-known complication of cerebral cysticercosis.
      The aim of this study was to explore the possible role of transcranial Doppler
      (TCD) in the evaluation of cysticercotic arteritis in 9 patients with
      subarachnoid cysticercosis and stroke. Arteritis of main basal vessels was
      detected by TCD in 7 of 10 arterial lesions that were demonstrated by cerebral
      angiography. The Doppler pattern was occlusive in 2 cases and stenotic in 5. In
      the 3 patients with lacunar infarcts, both cerebral angiography and TCD were
      normal. In 6 arterial lesions followed serially with TCD a stenotic pattern
      resolved within 4 and 6 months in 3 cases and remained in the stenotic range at
      12 months in 1 case, whereas an occlusive pattern persisted at 6 and 18 months in
      the other 2 cases. In conclusion, TCD may be useful to detect and follow up
      cerebral vasculitis due to chronic cysticercotic arachnoiditis.

PMID- 9645975
TI  - Predictive clinical factors of in-hospital mortality in 231 consecutive patients
      with cardioembolic cerebral infarction.
AB  - Cardioembolic cerebral infarction is a subtype of stroke with a high mortality.
      The purpose of this study was to determine predictors of in-hospital mortality in
      231 consecutive patients with cardioembolic stroke by means of a multivariate
      analysis. Three predictive models were constructed. A first model was based on
      demographic, anamnestic and clinical variables collected at the bedside
      examination (total 8 variables). A second model was based on clinical and
      neuroimaging variables (total 10 variables). A third model was based on the
      aforementioned clinical and neuroimaging variables and the presence of early
      recurrent embolism (total 11 variables). Deteriorated level of consciousness,
      limb weakness, presence of congestive heart failure, male gender, and age
      appeared to be independent prognostic factors of in-hospital mortality in the
      predictive model based on clinical variables and in the predictive model based on
      clinical and neuroimaging variables. In addition to these variables, early
      recurrent embolization was selected in the third predictive model. In the first
      two models, setting a cut-off point of 0.50 for predicting vital status at
      hospital discharge resulted in a sensitivity of 60%, a specificity of 89% and a
      total correct classification of 81%. The corresponding values of the third model
      were 62, 89 and 81%, respectively. These data may help clinicians to establish an
      early prognosis of this stroke subtype more accurately as well as to allocate
      patients with cardioembolic stroke in clinical trials correctly.

PMID- 9645976
TI  - Different vascular risk factor profiles among cortical infarcts, small deep
      infarcts, and primary intracerebral haemorrhage point to different types of
      underlying vasculopathy. A study from the L'Aquila Stroke Registry.
AB  - The type of small-vessel disease in small deep (lacunar) infarcts (SDIs) remains
      contentious as opposed to that in primary intracerebral haemorrhage (PICH), which
      is lipohyalinosis in most cases. Therefore, we compared risk factor profiles as
      indicators of underlying vessel pathology, between patients with SDI and patients
      with PICH, and those with a non-cardio-embolic infarct involving the cortex
      (CORTI). Multivariate regression analysis showed the diabetes mellitus [odds
      ratio (OR) 0.56; 95% confidence interval (CI) 0.34-0.90] and
      hypercholesterolaemia (OR 0.63; 95% CI 0.40-0.99) were more strongly associated
      with CORTI than with SDI. Carotid stenosis was associated with SDI in comparison
      with PICH (OR 7.5; 95% CI 1.02-54.94). Compared with PICH, CORTI was more
      strongly associated with diabetes mellitus (OR 3.27; 95% CI 1.38-7.76), carotid
      stenosis (OR 24.42; 95% CI 4.99-119.45), and hypercholesterolaemia (OR 3.12; 95%
      CI 1.47-6.65), whereas hypertension was associated with PICH (OR 0.37; 95% CI
      0.18-0.79). These data support the hypothesis that small-vessel atheromatosis
      rather than small-vessel lipohyalinosis underlies lacunar infarcts in most cases.

PMID- 9645977
TI  - Carotid endarterectomy does not affect long-term blood pressure: observations
      from the NASCET. North American Symptomatic Carotid Endarterectomy Trial.
AB  - The aim of the study was to examine how blood pressure is affected by carotid
      endarterectomy over a 2-year period. We analyzed the data from 997 patients who
      received best medical care alone and 999 patients who received best medical care
      plus carotid endarterectomy (CE). All patients were recruited by the North
      American Symptomatic Carotid Endarterectomy Trial and were followed at regular
      clinic visits. The mean blood pressure at baseline was 145.2/81.2 mm Hg for
      medically treated patients and 146.2/81.9 mm Hg for surgically treated patients.
      The mean systolic and diastolic pressures increased by approximately 2.5% in the
      first month following randomization, then decreased over the next year and then
      remained relatively uniform. Throughout follow-up, surgical patients had slightly
      higher blood pressures than medically treated patients. At the end of 2 years,
      the mean systolic pressures in the two treatment groups converged to 147.6 mm Hg.
      The mean diastolic pressure in the medical patients returned to its baseline
      value, whereas the surgical patients' blood pressure remained slightly elevated
      by 0.5 mm Hg. The percentage of patients on antihypertensive medications mirrored
      the rise and fall in blood pressures. A sharp decrease in medication (from 56 to
      43%) was observed in both treatment groups at 1 month. The percentage of patients
      on medication increased subsequently, with approximately 63% taking medication at
      the end of 2 years. CE does not affect long-term blood pressure. The use of
      antihypertensive medications appears to be the key component in blood pressure
      management. As hypertension is related to neurologic morbidity and mortality,
      strict regulation of blood pressure is extremely important in patients with
      cerebrovascular disease.

PMID- 9645978
TI  - Cerebral venous thrombosis complicated by hemorrhagic infarction: factors
      affecting the initiation and safety of anticoagulation.
AB  - BACKGROUND AND PURPOSE: Anticoagulation (AC) may improve outcome in cerebral
      venous thrombosis (CVT), even when complicated by pretreatment hemorrhagic
      infarction (HI). The HI characteristics which affect the decision to initiate AC
      therapy and its outcome are unknown. We reviewed our experience with AC treatment
      for patients with CVT and HI. METHODS: Retrospective study. RESULTS: Two groups
      of patients were compared: those who received AC (n = 6) and those who did not (n
      = 6). Hemorrhage volumes ranged from petechial to large (93 cm3) hematoma with
      mass effect. Anticoagulated patients received treatment a mean of 11.3 days after
      symptom onset. Each had exclusively extratemporal HI without midline shift and
      had stable hemorrhage volumes and clinical status for at least 24 h prior to AC.
      AC did not increase HI volume or worsen clinical outcome. All 6 non-AC patients
      had enlarging hematomas. Four of these 6 patients had temporal HI; and two
      required hematoma resection. CONCLUSIONS: AC therapy was avoided in CVT patients
      with HI that were located in the temporal lobe, caused midline shift or were
      enlarging. AC was safely initiated within several days in clinically stable
      patients with non-temporal-lobe HI of unchanging volume. We suggest that the
      location and unchanged volume on serial CT may be important factors influencing
      the safety of AC therapy in patients with CVT and HI.

PMID- 9645980
TI  - Clinical and ultrasonic long-term results of percutaneous transluminal carotid
      angioplasty. A prospective follow-up of 30 carotid angioplasties.
AB  - Experience of the long-term outcome of patients treated with carotid balloon
      angioplasty is limited. Therefore, we prospectively analyzed the ultrasonic and
      clinical features of 29 patients with complete follow-up data beyond 24 months,
      evaluated from 1989 through 1996 from our carotid angioplasty cohort of 106
      patients. Mean follow-up time was 33 months. For up to 78 months postangioplasty,
      23 patients with 24 angioplasties (77%) had no further neurological sequelae.
      Single ipsilateral amaurosis fugax or TIA events occurred in 3 patients.
      Recurrent ipsilateral amaurosis fugax or TIA events were noted twice in 2
      patients. No patient suffered an ipsilateral stroke. Fifteen angioplasties (50%)
      remained with normal ultrasound (stenosis < 50%), mild restenosis (50-70%)
      occurred in 12 angioplasties (40%), and severe restenosis (> 70%) in 3
      angioplasties (10%). Only in 2 of 15 patients clinical complications were related
      to the occurrence of ipsilateral restenosis above 50%. Until now, rigorous and
      careful evaluation of patients and clinical and ultrasonic follow-up have been
      essential for the estimation of the long-term efficacy of carotid angioplasty. It
      should be noted that carotid angioplasty is a new technique in evolution, with a
      high potential improving the technical results.

PMID- 9645979
TI  - Safety and tolerability of 619C89 after acute stroke.
AB  - BACKGROUND: 619C89 is a use-dependent sodium channel blocker which reduces
      hemispheric infarction volume by up to 60% after permanent middle cerebral artery
      occlusion in rats. Intravenous doses of up to 1 mg/kg have been well tolerated by
      healthy young and elderly volunteers. This study sought to assess safety and
      tolerability of 619C89 in the treatment of acute stroke. METHODS: Patients were
      randomised within 12 h of onset of stroke to receive 619C89 or placebo as an
      intravenous loading dose, followed by maintenance doses given 8 hourly for 64 h
      in a double-blind, ascending-dose tolerance study. Dosing commenced at 0.5 mg/kg
      loading plus 0.25 mg/kg/8 h maintenance for the first group and increased in
      increments of 0.5 mg/kg loading +0.25 mg/kg/8 h maintenance thereafter. Safety
      evaluation was continued for 3 months. RESULTS: 48 patients were recruited. 12
      received placebo and 36 received 619C89 in doses up to 2.5 mg/kg loading plus
      1.25 mg/kg/8 h. Dose escalation was stopped after the occurrence of
      hallucinations in 5 of 18 patients who received 2 mg/kg/8 h or more. Gastro
      intestinal upset and confusion were also possibly drug related. No drug-related
      effects on cardiovascular function were found. CONCLUSIONS: 619C89 was associated
      with significant central nervous system side-effects at doses of 2 mg/kg + 1
      mg/kg/8 h or greater as discrete intravenous infusions within 12 h of stroke
      onset. It may also cause gastro-intestinal side-effects. Doses below this are
      well tolerated in patients. No adverse cardiovascular effects were seen.

PMID- 9645981
TI  - Alpha-1-antitrypsin deficiency in spontaneous intracranial arterial dissections.
AB  - alpha 1-Antitrypsin deficiency has been associated with a variety of vascular
      disorders including arterial aneurysms, spontaneous extracranial arterial
      dissections, and arterial fibromuscular dysplasia. We determined the distribution
      of alpha 1-antitrypsin phenotypes in patients with intracranial arterial
      dissections, a rare cause of subarachnoid hemorrhage. The study population
      consisted of 4 consecutive patients with subarachnoid hemorrhage due to
      spontaneous intracranial arterial dissections. The vertebral artery was involved
      in 3 patients and the posterior inferior cerebellar artery in 1 patient. Three of
      these 4 patients were found to have a heterozygous alpha 1-antitrypsin deficiency
      (PiMZ or PiMS phenotypes). These data support previous studies suggesting that
      patients with alpha 1-antitrypsin deficiency may be at an increased risk of
      developing spontaneous arterial dissections.

PMID- 9645982
TI  - Thrombo-embolic stroke, moya-moya phenomenon and primary oxalosis.
AB  - We present the clinical, radiological and autopsy findings in a 32-year-old woman
      with primary oxalosis, who suffered recurrent bilateral carotid territory
      infarcts. The overall features were those of moya-moya syndrome, with bilateral,
      ultimately thrombotic, occlusion of the distal internal carotid arteries. Vessel
      pathology suggests an underlying intimal vasculopathy, the possible relation of
      which to the patient's metabolic abnormality is discussed.

PMID- 9645983
TI  - Cheiroretroauricular syndrome: a restricted form of pure sensory stroke due to a
      pontine hematoma.

PMID- 9645984
TI  - Severe preeclampsia/eclampsia: hypertensive encephalopathy of pregnancy?

PMID- 9645985
TI  - Neuroprotection as initial therapy in acute stroke. Third Report of an Ad Hoc
      Consensus Group Meeting. The European Ad Hoc Consensus Group.
AB  - Although a considerable body of scientific data is now available on
      neuroprotection in acute ischaemic stroke, this field is not yet established in
      clinical practice. At its third meeting, the European Ad Hoc Consensus Group
      considered the potential for neuroprotection in acute stroke and the practical
      problems attendant on the existence of a very limited therapeutic window before
      irreversible brain damage occurs, and came to the following conclusions.
      NEUROPROTECTANTS IN CLINICAL DEVELOPMENT: Convincing clinical evidence for an
      efficacious neuroprotective treatment in acute stroke is still required. Caution
      should be exercised in interpreting and extrapolating experimental results to
      stroke patients, who are a very heterogeneous group. The limitations of the time
      windows and the outcome measures chosen in trials of acute stroke therapy have an
      important influence on the results. The overall distribution of functional
      outcomes provides more statistical information than the proportion above a
      threshold outcome value. Neurological outcome should also be assessed.
      Neuroprotectants should not be tested clinically in phase II or phase III trials
      in a time window that exceeds those determined in experimental studies. The
      harmful effects of a drug in humans may override its neuroprotective potential
      determined in animals. Agents that act at several different levels in the
      ischaemic cascade may be more effective than those with a single mechanism of
      action. CURRENT IN-HOSPITAL MANAGEMENT OF ACUTE STROKE: The four major
      physiological variables that must be monitored and managed are blood pressure,
      arterial blood gas levels, body temperature, and glycaemia. The effects of
      controlling these physiological variables have not been studied in prospective
      trials, though they may all contribute to the outcome of acute ischaemic stroke
      and affect the duration of the therapeutic window. Optimal physiological
      parameters are inherently neuroprotective. Trials of new agents for the treatment
      of acute stroke should aim to maintain these physiological variables as close to
      normal as possible, and certainly within strictly defined limits. THE PLACE OF
      NEUROPROTECTANTS IN ACUTE STROKE MANAGEMENT: Stroke patients are a very
      heterogeneous group with respect to stroke mechanisms and severity, general
      condition, age and co-morbidities. At the present time, the only firm guideline
      than can be proposed for patient selection is the need for early admission to
      enable neuroprotectant and/or thrombolytic treatment to be started as soon as
      possible within the therapeutic window. The severity of potential side-effects
      will largely determine who should assess a patient with suspected stroke and
      initiate treatment. There is little information on which to base the duration of
      neuroprotectant therapy, and more experimental data are needed. Even if
      prehospital treatment proves to be feasible, it should not replace comprehensive
      stroke management in a specialist hospital unit. Clinical trials of
      neuroprotectants should only be performed in stroke units. The combined approach
      of restoring blood flow and providing neuroprotection may be the most productive
      in human stroke, but current clinical trial design will have to change in order
      to test combination therapy. Important side-effects are those that interfere with
      any possible benefit or increase mortality. PHARMACO-ECONOMIC ASPECTS OF
      NEUROPROTECTANTS: The early increase in hospital cost associated with
      neuroprotectant therapy may be balanced by the shorter length of hospital stay
      and lesser degree of disability of the surviving patients. The overall direct
      financial cost is highly dependent on the number of patients eligible for
      neuroprotectant therapy, which is itself dependent on the length of the
      therapeutic window and the severity of potential side-effects. A treatment that
      achieves a good functional outcome is the most cost-effective approach.

PMID- 9645986
TI  - Type 1 diabetes and enterovirus infections. Proceedings of a meeting. Helsinki,
      Finland.

PMID- 9645987
TI  - Accomplishments and challenges in picornavirology as observed by a medical
      doctor.
AB  - BACKGROUND: The family of picornaviridae has been studied extensively: the
      structure of the virion and its replication strategy are known in molecular
      detail. Nevertheless, infections with the multitude of enteroviruses still cause
      widespread epidemics, serious disease and a diversity of clinical syndromes
      ranging from central nervous system involvement to light febrile illness.
      Infections with more than 100 human rhinovirus types are an important economic
      factor. OBJECTIVE: In order to treat and control picornavirus infections with
      their great diversity of manifestations the pathogenesis of diseases must be
      better understood, e.g. concerning virus spread in the organism or molecular
      detail of the disease processes, such as cell tropism of the virus or cytokine
      and immunologic actions. Elucidation of mechanisms of virus transmission in the
      population is also needed. STUDY DESIGN: This review discusses aspects of our
      present knowledge of the pathogenesis, transmission, prophylaxis and treatment of
      picornavirus infections. CONCLUSIONS: The need for further development of
      selective antiviral substances, safe vaccines and basic research in
      picornavirology is stressed.

PMID- 9645988
TI  - Enterovirus infections and insulin dependent diabetes mellitus--evidence for
      causality.
AB  - BACKGROUND: Insulin-dependent diabetes mellitus (IDDM) has a long subclinical
      period characterised by gradually progressing autoimmune damage of insulin
      producing beta-cells. Clinical IDDM is manifested when 90% of beta-cells have
      been destroyed. Several studies have indicated that enterovirus infections,
      coxsackievirus B (CVB) infections especially, are frequent at the manifestation
      of clinical IDDM suggesting that they can precipitate the symptoms of IDDM in
      individuals who already have an advanced beta-cell damage. Recently, the first
      prospective studies have been published suggesting that enterovirus infections
      can also initiate the process several years before clinical IDDM. This implies
      that enterovirus infections may have a crucial role in the pathogenesis of human
      IDDM. OBJECTIVE: The recent findings have brought up the question whether the
      time has come when a causal association between enterovirus infections and IDDM
      could finally be confirmed. This review focuses on this question summarising the
      current knowledge and the prospects of future research. STUDY DESIGN: Review of
      the recent progress in studies evaluating the role of enterovirus infections in
      human IDDM. CONCLUSIONS: The currently available information supports the
      assumption that the role of enterovirus infections may be more important than
      previously estimated. Enterovirus infections are obviously associated with
      increased risk of IDDM, but whether this association reflects causal relationship
      remains to be confirmed in future studies. Prospective birth-cohort studies will
      be among the most important ones giving important data on the etiologic fraction
      of enterovirus infections, the properties of diabetogenic virus variants and the
      mechanisms of beta-cell damage.

PMID- 9645989
TI  - The pathogenesis of viral-induced diabetes.
AB  - Serologic case-control studies have suggested an association between coxsasckie
      group B viruses and insulin-dependent diabetes mellitus (IDDM). New
      investigations have identified enteroviral nucleic acid in the peripheral blood
      mononuclear cells of newly-diagnosed patients with IDDM. The disease pathogenesis
      is dependent on several factors. including the genetics of the host, strain of
      virus, activation status of autoreactive T-cells, upregulation of pancreatic MHC
      1 antigens, molecular mimicry between viral and beta cell epitopes and direct
      islet cell destruction by viral cytolysis. Epitopes (IDDM-E1 and E2) on glutamate
      decarboxylase 65 (GAD65) are the most common targets for antibody and cellular
      mediated autoimmune beta cell destruction.

PMID- 9645990
TI  - Molecular epidemiology of enteroviruses with special reference to their potential
      role in the etiology of insulin-dependent diabetes mellitus (IDDM). A review.
AB  - BACKGROUND: Several lines of evidence suggest that enterovirus infections may be
      involved in the etiology of the insulin-dependent diabetes mellitus (IDDM). Often
      in the literature, a reference is given to specifically diabetogenic strains of
      enterovirus but there is no systematic assessment about the generation of such
      strains in the course of evolution or about their abundance among the 64
      enterovirus serotypes pathogenic to man. If enteroviruses truly are involved in
      the etiology of IDDM, a possibility to prevent the disease with enterovirus
      vaccines might become feasible. In such a situation it would be important to know
      which serotypes and strains are the most important ones, and whether there would
      be differences between the strains as regards the pathogenetic mechanisms
      involved. OBJECTIVE: To present a brief summary of the basic biology of
      enteroviruses, on existing data of genetic variation of enteroviruses, and on
      molecular epidemiology of human enteroviruses with special reference to the
      different epidemiological modes of their putative involvement in the pathogenesis
      of IDDM. CONCLUSIONS: Like RNA viruses in general, enteroviruses exist as a
      quasispecies, a mixture of genetic microvariants with a vast potential to adapt
      to new environments. This means that specifically beta cell-tropic and
      potentially diabetogenic variants could, in theory, emerge sporadically during
      systemic infection of any individual. The patterns of genetic diversification of
      enteroviruses, cocirculation of separate genetic lineages in the human
      populations, and the assumed geographical restrictions of endemic transmission of
      the lineages, allow one to hypothesize that populations with a high persisting
      IDDM incidence might be endemically infected by some specific strains of
      enteroviruses. However, so far, there is no systematically collected data
      supporting this hypothesis.

PMID- 9645991
TI  - Nucleotide sequence of an attenuated mutant of coxsackievirus B3 compared with
      the cardiovirulent wildtype: assessment of candidate mutations by analysis of a
      revertant to cardiovirulence.
AB  - BACKGROUND: Coxsackievirus B3 (CVB3) causes myocarditis in the SWR (H2q) mouse
      model and persistence of CVB3 in myocardium disposes to the development of
      dilated cardiomyopathy. An attenuated strain of CVB3 has been isolated, sequenced
      and several candidate mutations for attenuation identified. Derivation of a
      revertant to cardiovirulence allows the significance of these mutations to be
      assessed. OBJECTIVES: To ascertain which candidate mutation(s) determine(s) the
      attenuated phenotype. STUDY DESIGN: A revertant to cardiovirulence was isolated
      following passage through severe combined immunodeficient disease (SCID) mouse
      heart. The 5'-non-translated region (NTR) and region coding for capsid proteins
      were sequenced and compared to the wildtype and attenuant. RESULTS: There are
      five candidates for attenuation: (1) A-G at base 580 in the 5'-NTR; (2) A-T at
      base 690 in the 5'-NTR; (3) CG-GC at bases 1401/2 (Thr to Ser at amino acid 151
      in VP2); (4) AA-GT at bases 2691/2 (Lys to Ser at amino acid 80 in VP1); (5) A-G
      at base 2916 (Asp to Gly at amino acid 155 in VP1). It was shown previously that
      mutations at 580, 690 and 2691/2 are not important in attenuation. Additionally,
      there are three novel mutations in the coding region of the revertant and one in
      the 5'-NTR which are unlikely to be relevant for attenuation as they are not
      present in the attenuant. Of nucleotide changes seen at 1401/2 and 2916 in the
      attenuant, only 2916 reverts to the wildtype sequence and so is a strong
      candidate for a determinant of attenuation.

PMID- 9645992
TI  - An approach to understanding the mechanisms of poliovirus persistence in infected
      cells of neural or non-neural origin.
AB  - BACKGROUND: Poliovirus (PV) is the etiologic agent of paralytic poliomyelitis,
      which is sometimes followed, after decades of clinical stability, by new
      symptoms, including progressive muscular atrophy, collectively known as the post
      polio syndrome. This raises the question of possible PV persistence in post polio
      patients. OBJECTIVE: To test the capacity of PV to establish persistent
      infections in human cells, three models were developed. STUDY DESIGN: This review
      focuses on the viral and cellular parameters involved in persistent PV infection.
      RESULTS: Many PV strains, which are generally lytic in primate cell lines, are
      able to establish persistent infections in human neuroblastoma cells. During
      persistent infection, PV mutants (PVpi) are consistently selected, and several of
      their capsid substitutions occur at positions known to be involved in PV-PV
      receptor interactions. PVpi have a particular property: they can establish
      persistent infections in non-neural HEp-2 cells. PV can also persistently infect
      primary cultures of human fetal brain cells and the majority of cells which
      survive infection belong to the neuronal lineage. CONCLUSIONS: The results
      obtained with the three models of persistent PV infection in human cells suggest
      that several mechanisms are used by PV to establish and maintain persistent
      infections in neural and non-neural cells. The interactions of the virus with its
      receptor seem to be a key-step in all cases. In the future, the elucidation of
      the etiology of the post-polio syndrome will require the characterization of PV
      sequences having persisted for decades in post-polio patients.

PMID- 9645993
TI  - Coxsackie B virus and its interaction with permissive host cells.
AB  - BACKGROUND: Observations in humans and the results of experiments on laboratory
      animals have provided evidence that coxsackieviruses of group B (CVB) are major
      etiologic agents of acute and chronic enterovirus myocarditis and various other
      virus-induced diseases. OBJECTIVE: This minireview briefly summarizes the
      investigations to elucidate various molecular mechanisms for the induction and
      maintenance of persistent CVB infections. With regard to the recent findings that
      CVB may use several different receptor proteins, this article focuses on virus
      host cell interactions and the potential impact of these interactions for
      enteroviral replication. STUDY DESIGN: The interaction of CVB with specific cell
      surface proteins was analyzed in cultured cell lines and murine tissues at the
      level of virus attachment and virus internalization. As example for the
      interaction of CVB with intracellular proteins, the state of p21rasGTPase
      activating protein (RasGAP) was investigated in mock-infected and CVB3-infected
      HeLa cells. RESULTS AND CONCLUSIONS: The experiments to elucidate the virus
      receptor interactions revealed the necessity to differentiate between CVB
      attachment proteins and proteins involved in virus internalization. Since more
      than one protein may be required to initiate the uptake of CVB into permissive
      host cells, a model of the putative interaction of these proteins within a
      multimeric receptor complex is proposed. It is further tempting to speculate that
      the presence of multiple attachment proteins may influence the tissue tropism of
      CVB as well as pathogenicity.

PMID- 9645994
TI  - Coxsackie B virus infection and beta cell autoantibodies in newly diagnosed IDDM
      adult patients.
AB  - BACKGROUND: Environmental agents such as viruses have been identified as
      potentially important determinants of insulin-dependent diabetes mellitus (IDDM).
      Enterovirus infections, Coxsackievirus B especially, could be linked to the beta
      cell damaging process and to the onset of clinical IDDM. OBJECTIVES: Enteroviral
      (EV) infection and beta cell autoimmunity were studied in adult patients at the
      onset of IDDM. STUDY DESIGN: A total of 14 newly diagnosed-IDDM patients with
      ketosis or ketoacidosis were compared to, anteriorly diagnosed IDDM patients with
      metabolic decompensation, non-IDDM patients with metabolic decompensation and
      healthy adults. EV infection was studied by genomic RNA detection in whole blood
      using a RT-PCR assay. In order to assess the level of beta cell autoantibodies at
      the time of the initial metabolic decompensation, serum specimens from IDDM
      patients were tested for GAD65 antibodies and islet cell antibodies (ICAs).
      RESULTS: Coxsackie B3 or B4 virus genome was detected and genotyped in five of 14
      (35.7) newly diagnosed IDDM patients and in one of 12 (8%) patients in the course
      of IDDM. By contrast, none of the 12 non-IDDM patients and none of the 15 healthy
      adults was positive for enterovirus RNA detection in whole blood. Positive GAD65
      antibodies and ICAs assays were not significantly correlated to a positive EV-RNA
      detection. CONCLUSION: The present study demonstrates that Coxsackie B virus RNA
      sequences can be detected in the peripheral blood from adult patients at the
      onset or in the course of IDDM and suggests that a Coxsackie B virus infection
      could initiate or accelerate beta cell autoimmune damaging process.

PMID- 9645995
TI  - Development of an enterovirus specific PCR method for the quantification of
      enterovirus genomes in blood of diabetes patients.
AB  - BACKGROUND: Insulin-dependent diabetes mellitus or type 1 diabetes is a disease
      with a diverse aetiology. Epidemiological studies examining newly diagnosed,
      recent onset IDDM patients have suggested a role for viruses in the aetiology of
      IDDM (Yoon, 1995, Diabetes/Metabolism Reviews 11, 83-107). Important candidates
      are the enteroviruses, in particular coxsackieviruses B3 and B4. The latter can
      cause diabetes in animals (Clements et al., 1995, Lancet 346, 221-223).
      OBJECTIVES: We have developed a quantitative PCR method for the detection of
      enterovirus genomes in biological samples. The quantitative PCR will be used to
      screen for enteroviruses in blood of diabetes patients and their relatives by
      testing a Blood Diabetes Register. STUDY DESIGN: A substantial amount of data has
      been collected on enterovirus induced IDDM, our study is original in so far as it
      will be: (1) a quantitative study, not only the presence of viral genome
      sequences in blood will be determined, but also their concentrations (viral
      load); and (2) a longitudinal study, samples are and will be collected as a
      function of time. Positive PCR samples will be quantified using the standard
      addition method. RESULTS: The test is specific for enteroviruses, since all
      enteroviruses were detected with equal sensitivity. Viruses belonging to other
      picornavirus genera scored negative (even up to 3 x 10(6) genome copies). An
      equal detection limit of 10 genome copies was found for all enteroviruses.
      CONCLUSIONS: The developed method will permit us to generate quantitative and
      longitudinal data of enterovirus genomes in blood of diabetes patients and their
      relatives, which might help in the elucidation of the relationship between
      enteroviruses and IDDM.

PMID- 9645996
TI  - Demonstration of persistent enterovirus in the pancreas of diabetic mice by in
      situ polymerase chain reaction.
AB  - BACKGROUND: Although Enterovirus (EV) do not persist in the tissue, which is
      essential to maintain autoimmunity, they have been associated as the cause of
      chronic autoimmunity in some cases of insulin dependent diabetes mellitus (IDDM).
      Convincing reports, demonstrating persistent EV infections in the pancreases, are
      rare. OBJECTIVES: To determine the role of EV in IDDM, a mouse model was tested
      and i situ polymerase chain reaction (ISPCR) developed. The major problem of
      ISPCR are the high amounts of non-specific staining. In the current study we
      developed an ISPCR protocol which minimised non-specific staining and allowed the
      accurate localisation of the viral RNA in the tissue. STUDY DESIGN: Five mice
      were infected with coxsackievirus group B4, sacrificed 7 weeks later and the
      pancreases were harvested. The EV nucleic acid were localised and detected in the
      pancreases by ISPCR. RESULTS: In the current study non-specific staining of
      ISPCR, due to DNA repair and diffuse artefacts, were minimised and the EV nucleic
      acids were localised in the beta cells of the endocrine pancreases in all five
      diabetogenic mice. CONCLUSION: This study demonstrates an association of viral
      RNA with the development of diabetes in mice and the usefulness of ISPCR to
      determine the role of EV in IDDM.

PMID- 9645997
TI  - Diagnosis of cytomegalovirus infection in HIV-infected patients with respiratory
      disease.
AB  - BACKGROUND: The role of the cytomegalovirus (CMV) in the respiratory morbidity
      and mortality of HIV-infected patients remains unclear. This is due in part to
      difficulties in making an accurate and rapid diagnosis. There has been a limited
      number of studies, often with few or no AIDS patients, on the use of DNA-DNA in
      situ hybridization (ISH) and polymerase chain reaction to diagnose CMV
      respiratory infection directly on bronchoalveolar fluid samples. OBJECTIVES: To
      compare the centrifugation culture (CC), ISH, and nested-primer polymerase chain
      reaction (npPCR) techniques (npPCR) techniques on bronchoalveolar fluid for the
      diagnosis of respiratory CMV infection. STUDY DESIGN: Samples were obtained
      prospectively from a group of 35 HIV-infected homosexual men evaluated for
      pneumonia at a university hospital. Sensitivity, specificity, and predictive
      values of the three techniques were measured and compared, using the conventional
      roller tube cell culture (CRTC) as the gold standard. RESULTS: Sensitivity,
      specificity, positive and negative predictive values were as follows: 86%, 86%,
      90%, and 80% for the CC; 5%, 100%, 100%, and 41% for ISH; and 86%, 57%, 75%, and
      73% for npPCR. Of the six false positive samples by npPCR, two were positive by
      CC (none by ISH). If the latter were considered true positives, the specificity
      and positive predictive values of npPCR would increase to 67% and 83%,
      respectively. CONCLUSIONS: CC appeared to be the best of the three techniques
      compared in this study for diagnosis of respiratory CMV infection in HIV-infected
      patients. The sensitivity and predictive values of DNA-DNA ISH were very poor.
      Results with npPCR were acceptable, and this technique may be considered in
      situations when rapid diagnosis of CMV infection is necessary.

PMID- 9645998
TI  - Cell-fusion assay for the detection of rubella virus in Vero cells.
AB  - BACKGROUND AND OBJECTIVES: Rubella virus (RV) produces a subtle and slow
      developing cytopathic effect in Vero cells that is difficult to recognize,
      especially at low multiplicities of infection. In order to facilitate the
      detection of RV in cell culture, we standardized a low-pH virus-mediated cell
      fusion assay. STUDY DESIGN: The incubation periods, temperatures, pH and
      multiplicity of infection were established. The specificity of the method was
      tested by immunofluorescence assay and cell-fusion inhibition by specific sera.
      RESULTS: Six days post infection, Vero cells were treated for 5 min with fusion
      medium. After that, monolayers were incubated with medium at neutral pH for 16 h
      and then stained. Gigantic cells with multiple nuclei were observed. CONCLUSIONS:
      The method allowed the observation of unequivocal images that are easier to
      recognize than the cytopathic effect caused by RV in the same cell line. At the
      same time, the method is simple, accessible and shown to be specific to
      demonstrate the replication of several strains and isolates of RV in Vero cells.

PMID- 9645999
TI  - Acute lower respiratory infections due to respiratory syncytial virus and
      adenovirus among hospitalized children from Argentina.
AB  - BACKGROUND: Acute lower respiratory infection (ALRI) is one of the main causes of
      morbidity and mortality in small children. OBJECTIVE: The aim of this study was
      to determine the frequency, seasonality and association with clinical entities of
      respiratory syncytial virus (RSV) and adenoviruses in children with ALRI. STUDY
      DESIGN: During 2 consecutive years (1991-1992), 168 children under 2 years of age
      hospitalized due to ALRI in a public pediatric hospital of Buenos Aires,
      Argentina, were studied. RSV and adenoviruses were investigated on nasopharyngeal
      aspirates (NPA) by indirect immunofluorescence (IIF). HEp-2 cells were used for
      adenovirus isolation. RESULTS: RSV was detected in 36.3% and adenoviruses in
      14.3% of the cases (P < 0.0001). All adenoviruses detected by IIF were also
      isolated in culture. Out of 61 RSV cases, 57% corresponded to bronchiolitis and
      43% to pneumonia. Ninety-two per cent of children with RSV were less than 1 year
      old and 70% were less than 5 months. The highest number of RSV cases were
      observed during winter, with a clear peak in July. Seventy-one per cent of
      adenovirus cases were associated with pneumonia and only 24% with bronchiolitis
      (P < 0.02), and predominated in children older than 5 months of age (P < 0.0001).
      Adenoviruses were detected in almost all months of the year with a small peak at
      the end of winter and beginning of spring. No significant differences in clinical
      features at admission, breast feeding or malnutrition were observed among
      children with RSV or adenovirus diagnosis versus those with no viral etiology.
      The overall fatality rate was 2.4%. In all fatal cases adenovirus was detected in
      NPA. Thus, fatality rate among patients with adenoviruses reached 16.7%.
      CONCLUSIONS: Our findings show the importance of RSV and adenoviruses associated
      with ALRI in hospitalized children under 2 years of age and the different
      epidemiological patterns of the two viruses in Buenos Aires, Argentina.

PMID- 9646000
TI  - The clinical utility of viral quantitation using molecular methods.
AB  - BACKGROUND: The quantitation of viral nucleic acids in biological fluids has
      become increasingly desirable over the past several years. To this end, a number
      of quantitative molecular procedures have been developed. OBJECTIVES: The
      objective was to review the current literature on the molecular techniques used
      in the quantitation of viral nucleic acids and to assess the appropriateness of
      these methods for clinical use. RESULTS: Assays involving both target and signal
      amplification are now available for the accurate and precise quantitation of
      viral burden in infected patients. These methods include quantitative polymerase
      chain reaction (PCR), branched chain signal amplification (bDNA), nucleic acid
      sequence-based amplification (NASBA) and the SHARP signal and hybrid capture
      systems. Our understanding of the natural history and pathogenesis of viruses
      such as the human immunodeficiency virus (HIV), hepatitis B virus (HBV),
      hepatitis C virus (HCV), cytomegalovirus (CMV) and Epstein-Barr virus (EBV) may
      be greatly facilitated by accurate determinations of viral and infected cell
      burden. Quantitation of viral load in infected individuals may also be useful to
      assess disease progression, monitor the efficacy of therapy and to predict
      treatment failure and the emergence of drug-resistant viruses. CONCLUSION:
      Precise, accurate and reproducible quantitation of viral load is now feasible.
      Molecular assays for viral quantitation should have a considerable impact on
      medical research and clinical care.

PMID- 9646001
TI  - Human papillomavirus detection in cervical intraepithelial neoplasia by the
      second-generation hybrid capture microplate test, comparing two different
      cervical specimen collection methods.
AB  - BACKGROUND: The second generation Hybrid Capture microplate-based human
      papillomavirus (HPV) test (HC II) was examined to determine its sensitivity for
      identification of cervical intraepithelial neoplasia (CIN) by two different
      cervical specimen collection methods. OBJECTIVES: A cohort of 115 women with a
      mean age of 34.6 years (SD 9.1), referred to colposcopy with a history of
      abnormal cytology, was studied to compare HPV prevalence and viral load in low
      grade CIN vs. high grade CIN. STUDY DESIGN: Prior to the application of acetic
      acid, cervical specimens were obtained by either method 1 or 2, as follows:
      method 1: A cotton-tipped swab was applied to the ectocervix and endocervix for a
      Papanicolaou (Pap) smear. Next, a special cone-shaped cervical brush was applied
      to the endocervix, the ectocervix, and to the posterior vaginal vault and
      suspended in 1.0 ml of transport medium for HPV testing. Method 2: a Pap smear
      was taken with a cyto standard cylindrical cytology brush from the endocervix,
      and ectocervix, and the remaining cells were suspended in 3 ml phosphate-buffered
      saline (PBS) for HPV testing. Next, a Dacron-tipped swab was used to take a
      specimen from the ectocervix and posterior fornix and suspended in the same PBS
      solution.

PMID- 9646002
TI  - Serious respiratory illness associated with rhinovirus infection in a pediatric
      population.
AB  - BACKGROUND: Rhinoviruses have long been associated with mild upper respiratory
      illness in both adults and children. However, the role of rhinoviruses as lower
      respiratory tract pathogens has not been fully characterized. Previous data
      suggests that rhinoviruses may cause severe lower respiratory illness in young
      children or infants. OBJECTIVES: The present study describes the clinical
      presentations, severity of illness and outcomes for a large cohort of pediatric
      patients with documented rhinovirus infections. SUBJECTS AND METHODS: A
      retrospective chart review was done on 93 pediatric patients from whom 101
      nasopharyngeal or endotracheal specimens were positive by viral culture for a
      rhinovirus. All patients were hospitalized or seen in the pediatric emergency
      department at The Children's Hospital of Philadelphia between 1 January, 1990 and
      31 May, 1996. RESULTS: Of the 93 patients, 52 were male and 41 female. The age
      range was 0 days to 18 years with 25 (27%) less than 3 months, 42 (45%) between 3
      and 12 months and 26 (28%) over the age of 12 months. Clinical presentations on
      evaluation in the emergency department or admission included 78 (84%) patients
      with acute respiratory illness, 13 (17%) with fever and suspected sepsis and 11
      (12%) with other complaints. Reported physical findings on examination included
      one or more lower respiratory symptoms or signs of acute distress and fever
      greater than or equal to 38.1 degrees C. A total of 64 (69%) children were noted
      to have significant past medical histories, including 28 (44%) with prematurity
      or complicated neonatal courses, 11 (17%) with prior reactive airways, 8 (12%)
      with congenital cardiac disease and 7 (11%) with neurologic disorders. Of the
      patients, 29 (31%) were considered to be otherwise healthy children with no
      underlying dysfunctions. The mean duration of hospitalization for 69 patients
      admitted with respiratory illness who did not develop subsequent unrelated
      complications was 3.7 days. No significant bacterial or fungal pathogens were
      identified in 91% of the cases. CONCLUSIONS: This study shows that rhinoviruses
      were associated with severe lower respiratory illness and hospitalization in a
      large pediatric population and that rhinovirus infection was a complicating
      factor in those patients with underlying or predisposing conditions.

PMID- 9646003
TI  - Rapid detection, culture-amplification and typing of herpes simplex viruses by
      enzyme immunoassay in clinical samples.
AB  - BACKGROUND: The laboratory diagnosis of herpes simplex infection may require
      rapid (direct) tests, as well as cell cultures, for detection of the virus in
      clinical samples. The quantity of virus present in clinical samples is variable
      and this may depend on the period from onset of rash. In addition, not all
      patients may show obvious symptoms with this infection. The successful culture of
      herpes simplex virus requires prompt transportation after collection of the
      specimen as the virus is easily inactivated. Hence, rapid and culture tests would
      enable detection of non-viable and viable viruses. STUDY DESIGN: We describe the
      rapid detection of HSV by EIA directly in various clinical samples using
      commercially available polyclonal sera. In addition specimens were inoculated in
      microwell cell cultures and 4 days post inoculation the culture fluids were
      tested for HSV and subtyped by a similar EIA (culture amplified EIA). RESULTS:
      The direct EIA showed an endpoint detection of 100 TCID50/ml, sensitivity of 92%
      (all specimen types) and specificity of 100%. The direct EIA sensitivity was 97%
      in non-genital specimens and 88% in genital specimens. The culture amplified EIA
      showed a sensitivity of 95% compared to all confirmed HSV positive samples.
      CONCLUSIONS: The results of the HSV rapid tests were available within 24 h from
      receipt of specimens. Specimens which were culture negative/direct EIA positive
      were confirmed by blocking antisera. Culture positive specimens which were direct
      EIA negative were confirmed by subtyping of the virus.

PMID- 9646004
TI  - Evaluation of capture ELISA and rapid immunochromatographic test for the
      determination of IgM and IgG antibodies produced during dengue infection.
AB  - BACKGROUND: Rapid diagnosis of dengue infection is essential to patient
      management and disease control. The development of a rapid (5 min)
      immunochromatographic test and a 2 h commercial capture enzyme linked
      immunosorbent assay (ELISA) for anti-dengue IgM and IgG antibodies may lead to
      more rapid and accurate testing in peripheral health settings and diagnostic
      laboratories. OBJECTIVES: Evaluate two new commercial tests for dengue serology
      (Dengue Rapid test and Dengue Duo ELISA; PanBio, Brisbane, Australia). STUDY
      DESIGN: The sensitivity and specificity of the tests were compared with in-house
      dengue IgM ELISA and hemagglutination-inhibition (HAI) assays using known
      positive and negative dengue specimens, as well as specimens from non-dengue
      cases. RESULTS: Both assays showed excellent sensitivity in the diagnosis of both
      primary and secondary dengue infection (100%). In both assays, IgG levels showed
      excellent correlation with the hemagglutination-inhibition (HAI) assay, and these
      could be used to distinguish between primary and secondary dengue infections (92
      and 97% of patients correctly classified in the rapid test and Duo ELISA,
      respectively). Specificity in both assays was 89% when sera from patients, with
      no apparent dengue infection, typhoid, leptospirosis and malaria, were tested.
      CONCLUSIONS: These tests should be a useful aid in confirming the clinical
      diagnosis of dengue infection. The rapid test will be particularly valuable in
      peripheral health settings, while the ELISA has a place in central testing
      laboratories.

PMID- 9646005
TI  - Evaluation of Puumala virus IgG and IgM enzyme immunoassays based on recombinant
      baculovirus-expressed nucleocapsid protein for early nephropathia epidemica
      diagnosis.
AB  - BACKGROUND: Puumala virus (PUU), a member of Hantavirus genus, is the causative
      agent of nephropathia epidemica (NE), a milder form of hemorrhagic fever with
      renal syndrome (HFRS). Rapid diagnosis is essential for clinical management of
      NE. OBJECTIVES: To evaluate the usefulness of recombinant protein-based IgM
      (direct- and mu-capture) and IgG (direct-and antigen (Ag)-capture) enzyme
      immunoassays (EIA) in early diagnosis of NE in comparison to IgG
      immunofluorescence assay (IF), and to find out the time limit for PUU-specific
      antibody seroconversion. STUDY DESIGN: The specific IgM and IgG antibody
      responses in serum were analyzed in 109 patients (235 serial sera) and 114
      patients (233 serial sera), respectively. The serum panel used was selected from
      a larger material according to the availability of information concerning the
      date after onset of symptoms, the panel also containing NE patients who had been
      IgG-IF negative in their first (early) samples to find out the possible
      differences between sensitivities of the EIAs and IF. RESULTS: All NE patients
      tested became IgM-positive at the latest on the 6th (mu-capture EIA) or 7th
      (direct-IgM EIA) day after onset of symptoms. Out of a panel of very early NE
      patient sera (n = 38) that could not be detected by IgG-IF, 66% were already
      positive with both direct-IgM EIA and mu-capture EIA. When comparing IgG EIAs and
      IgG-IF, 98% of IF-positive sera from NE patients were also positive with direct
      IgG EIA, and 99% with Ag-capture IgG EIA. Out of a panel of very early NE-patient
      sera (n = 37) that could not be detected by IgG-IF, 57% were positive with direct
      IgG EIA, and 27% with Ag-capture IgG EIA. CONCLUSIONS: The baculovirus-expressed
      PUU-N-based IgG and IgM EIAs were found most suitable for NE diagnosis, giving
      the opportunity in some cases for earlier diagnosis as compared with PUU-IgG IF.

PMID- 9646006
TI  - Clinical pharmacokinetics of lornoxicam. A short half-life oxicam.
AB  - Lornoxican (chlorotenoxicam) is a nonsteroidal anti-inflammatory drug (NSAID) of
      the oxicam class. Unlike other oxicams, lornoxicam has a relatively short plasma
      half-life (3 to 5 hours). Lornoxicam is eliminated following biotransformation to
      5'-hydroxy-lornoxicam, which does not undergo enterohepatic recirculation.
      Glucoroconjugated metabolites are excreted in urine and faeces with a half-life
      of about 11 hours. Lornoxicam and its metabolites bind extensively to plasma
      albumin. Substantial concentrations of lornoxicam are attained in synovial fluid,
      the proposed site of action in chronic inflammatory arthropathies. The effects of
      lornoxicam concentration on its therapeutic and toxicological properties have not
      yet been extensively reported. Lornoxicam, like other NSAIDs, appears to interact
      with warfarin, sulphonylureas, digoxin and furosemide.

PMID- 9646007
TI  - Clinical pharmacokinetics of mycophenolate mofetil.
AB  - The pharmacokinetics of the immunosuppressant mycophenolate mofetil have been
      investigated in healthy volunteers and mainly in recipients of renal allografts.
      Following oral administration, mycophenolate mofetil was rapidly and completely
      absorbed, and underwent extensive presystemic de-esterification. Systemic plasma
      clearance of intravenous mycophenolate mofetil was around 10 L/min in healthy
      individuals, and plasma mycophenolate mofetil concentrations fell below the
      quantitation limit (0.4 mg/L) within 10 minutes of the cessation of infusion.
      Similar plasma mycophenolate mofetil concentrations were seen after intravenous
      administration in patients with severe renal or hepatic impairment, implying that
      the de-esterification process had not been substantially affected. Mycophenolic
      acid, the active immunosuppressant species, is glucuronidated to a stable
      phenolic glucuronide (MPAG) which is not pharmacologically active. Over 90% of
      the administered dose is eventually excreted in the urine, mostly as MPAG. The
      magnitude of the MPAG renal clearance indicates that active tubular secretion of
      MPAG must occur. At clinically relevant concentrations, mycophenolic acid and
      MPAG are about 97% and 82% bound to albumin, respectively. MPAG at high (but
      clinically realisable) concentrations reduced the plasma binding of mycophenolic
      acid. The mean maximum plasma mycophenolic acid concentration (Cmax) after a
      mycophenolate mofetil 1 g dose in healthy individuals was around 25 mg/L,
      occurred at 0.8 hours postdose, decayed with a mean apparent half-life (t1/2) of
      around 16 hours, and generated a mean total area under the plasma concentration
      time curve (AUC infinity) of around 64 mg.h/L. Intra- and interindividual
      coefficients of variation for the AUC infinity of the drug were estimated to be
      25% and 10%, respectively. Intravenous and oral administration of mycophenolate
      mofetil showed statistically equivalent MPA AUC infinity values in healthy
      individuals. Compared with mycophenolic acid, MPAG showed a roughly similar Cmax
      about 1 hour after mycophenolic acid Cmax, with a similar t1/2 and an AUC
      infinity about 5-fold larger than that for mycophenolic acid. Secondary
      mycophenolic acid peaks represent a significant enterohepatic cycling process.
      Since MPAG was the sole material excreted in bile, entrohepatic cycling must
      involve colonic bacterial deconjugation of MPAG. An oral cholestyramine
      interaction study showed that the mean contribution of entrohepatic cycling to
      the AUC infinity of mycophenolic acid was around 40% with a range of 10 to 60%.
      The pharmacokinetics of patients with renal transplants (after 3 months or more)
      compared with those of healthy individuals were similar after oral mycophenolate
      mofetil. Immediately post-transplant, the mean Cmax and AUC infinity of
      mycophenolic acid were 30 to 50% of those in the 3-month post-transplant
      patients. These parameters rose slowly over the 3-month interval. Slow metabolic
      changes, rather than poor absorption, seem responsible for this nonstationarity,
      since intravenous and oral administration of mycophenolate mofetil in the
      immediate post-transplant period generated comparable MPA AUC infinity values.
      Renal impairment had no major effect on the pharmacokinetic of mycophenolic acid
      after single doses of mycophenolate mofetil, but there was a progressive decrease
      in MPAG clearance as glomerular filtration rate (GFR) declined. Compared to
      individuals with a normal GFR, patients with severe renal impairment (GFR 1.5
      L/h/1.73m2) showed 3-to 6-fold higher MPAG AUC values. In rental transplant
      recipients during acute renal impairment in the early post-transplant period, the
      plasma MPA concentrations were comparable to those in patients without renal
      failure, whereas plasma MPAG concentrations were 2- to 3-fold higher.
      Haemodialysis had no major effect on plasma mycophenolic acid or MPAG. Dosage
      adjustments appear to not be necessary either in renal impairment or during
      dialysis. (ABSTRACT TRUN

PMID- 9646009
TI  - Clinical pharmacokinetics of neuromuscular relaxants in pregnancy.
AB  - Despite an increased in bodyweight, plasma volume by 45% and blood volume by 35%
      that might influence the volume of distribution of polar drugs, the apparent
      volume of distribution at steady state (Vss), volume of distribution (Vd) and the
      apparent volume of the central compartment (Vc) of atracurium, vecuronium and
      pancuronium are unchanged during pregnancy. With an elimination that is
      independent of renal, hepatic and enzymatic functions, the clearance of
      atracurium is also unchanged. This is corroborated by an unchanged clinical
      duration of atracurium during pregnancy. The clearance of pancuronium is
      increased by 27% during caesarean section. This may be explained by the increased
      glomerular filtration rate reported in pregnant women. The clinical duration of
      vecuronium in term and postpartum women is twice that reported in nonpregnant
      women. On the other hand, an increase in the clearance clearance of vecuronium
      during cesarean sections has been reported. The umbilical/maternal vein
      concentration ratio (UV/MV) of nondepolarising neuromuscular relaxants varies
      from 7 to 26% and clinical doses of these drugs may induce partial residual
      curarisation in neonates. Fetal concentrations of non-depolarising neuromuscular
      relaxants are proportional to the maternal dose injected as demonstrated for
      pancuronium and vecuronium. Increasing UV/MV with longer drug injection to
      delivery intervals have been demonstrated for drugs with a high molecular weight,
      such as atracurium, but not for those with a low molecular weight, such as
      vecuronium, while conflicting results have been reported for pancuronium. Despite
      decreased plasma pseudocholinesterases, the clinical duration of succinylcholine
      1 mg/kg is unchanged in pregnant women, and only is slightly increased in
      postpartum women. On the other hand, larger doses of succinylcholine have induced
      prolonged apnoea and phase II block. The use of a pretreatment dose of a
      nondepolarising neuromuscular relaxant to decrease fasciculations and subsequent
      postoperative muscle pain is not only unnecessary in pregnant women but may be
      hazardous, since it may produce unexpected significant curarisation with
      respiratory distress. At clinical doses, transplacental passage of
      succinylcholine is insufficient to produce curarisation of neonates except in
      those born to mothers with abnormal plasma pseudocholinesterases. Magnesium
      sulfate, used in the treatment of pre-eclampsia, will enhance the blocking
      effects of nondepolarising neuromuscular relaxants but will have no effects on
      the characteristics of paralysis of succinylcholine. Histamine type 2 antagonists
      used to decrease the risk of aspiration during induction of anaesthesia do not
      influence the blocking properties of neuromuscular relaxants, while
      metoclopramide prolongs the block of succinylcholine.

PMID- 9646010
TI  - Therapeutic drug monitoring of clozapine treatment. Therapeutic threshold value
      for serum clozapine concentrations.
AB  - It has been suggested that the minimum effective serum clozapine concentration
      for an acceptable clinical response (threshold value) is about 400 micrograms/L.
      This article argues against the use of therapeutic drug monitoring (TDM) as a
      tool to obtain clozapine concentrations of > or = 400 micrograms/L in the
      individual patient from the start of clozapine treatment. The following arguments
      are presented: (i) because of a great interindividual variability of the
      clozapine concentration to dose ratio (C/D) it can be calculated that extremely
      high daily doses (900 to 1800 mg/day) would be necessary in 15% of patients to
      obtain a clozapine concentration of 400 micrograms/L; (ii) doses of 200 to 300
      mg/day are commonly used in Central Europe. although about 80% of the patients
      can be expected to have clozapine concentration < 400 micrograms/L; (iii) in a
      double-blind study, no difference in clinical response was found between patients
      treated with clozapine in the concentration range of 200 to 300 micrograms/L, and
      a group with higher clozapine concentrations; (iv) positron emission topography
      (PET) studies indicate that maximum receptor occupancy is obtained at clozapine
      concentrations of about 200 micrograms/L and no further receptor occupancy is
      obtained by increasing clozapine concentrations to > or = 400 micrograms/L; (v)
      the frequency of both severe clozapine-induced adverse effects (seizure and
      confusion) and more common adverse effects increases with increasing
      doses/clozapine concentrations. It is concluded that the antipsychotic effects
      and adverse effects of clozapine occur over a very broad range of serum
      concentrations. In most countries the majority of patients are treated with
      clozapine concentrations well below the 400 micrograms/L suggested as threshold
      concentration for optimum response. Therefore clinical judgement should always be
      primarily used for dose adjustments. TDM is useful to follow compliance and to
      adjust for extreme serum concentrations and revealing drug interactions.

PMID- 9646012
TI  - Mikulas Teich: a biographical sketch.

PMID- 9646013
TI  - Business history: Cinderella, prince charming or ugly sister?

PMID- 9646011
TI  - Pharmacokinetic optimisation of the treatment of neurocysticercosis.
AB  - Neurocysticercosis is the most important parasitic infection of the nervous
      system. It is common in communities living in conditions with poor hygiene. Until
      the last 2 decades, there was no specific pharmacological treatment: surgery and
      corticosteroids were the only medical alternatives. The recent introduction of
      anticysticercal drugs, an isoquinoline (praziquantel) and a benzimidazole
      (albendazole), has dramatically changed the medical management of
      neurocysticercosis. Praziquantel is taken orally and undergoes extensive first
      pass hepatic biotransformation. Peak concentration in serum is reached after 1 to
      2 hours and the elimination half-life is between 1 and 3 hours. Praziquantel
      permeates the blood-brain barrier, thus explaining its effectiveness on
      parenchymal brain cysticercosis. Plasma concentrations of the drug are increased
      when a high carbohydrate diet is administered. Cimetidine also increases the
      plasma concentration of praziquantel by inhibition of cytochrome P450.
      Bioavailability of the drug is markedly reduced when given jointly with
      antiepileptics or corticosteroids, specially carbamazepine, phenytoin or
      dexamethasone. The current schedule for neurocysticercosis treatment lasts 2
      weeks at daily doses of 50 mg/kg. Recently, a new therapeutic scheme has been
      proposed that considers the pharmacokinetics of the drug. This regime lasts only
      1 day and includes 3 dosages of 25 mg/kg at 2-hour intervals. This increases the
      time that the parasite is exposed to high drug concentrations. This therapeutic
      scheme has produced similar results to longer schemes, with the additional
      advantages of cost, length of usual treatments and reduction in total dose
      received (being one-tenth of the total dosage). Albendazole is considered by many
      as the drug of choice for treatment of neurocysticercosis. It is given orally and
      is rapidly and extensively metabolised to albendazole sulfoxide (ALBSO), which is
      considered to be the metabolite directly or indirectly responsible for both
      toxicity and efficacy outside the gastrointestinal tract. Concentrations of ALBSO
      are highly variable between individuals and it has a half-life of between 6 and
      15 hours. It also crosses the blood-brain barrier. In patients with extrahepatic
      obstruction, the elimination process is prolonged and plasma concentration is
      increased. Fatty meals improve absorption. Concomitant administration of
      albendazole with dexamethasone or with praziquantel increases plasma
      concentration of ALBSO. Albendazole is administered in an 8 day course of 15
      mg/kg per day in 2 divided doses 12 hours apart. This scheme, based on drug
      pharmacokinetics, has proven to be highly effective. Inflammation is a common
      accompaniment of neurocysticercosis; in many cases it is the aetiopathogen
      responsible for histological damage. Corticosteroid therapy is useful for
      preventing further tissue injury. Long term corticosteroid therapy can be
      accomplished with 50 mg of oral prednisone 3 times a week. Acute corticosteroid
      therapy includes brief courses with high dosages of intramuscular dexamethasone
      or intravenous methylprednisolone. Clinical decisions on cysticidal and anti
      inflammatory treatments must be made with the information gathered by
      neuroimaging studies, either computed tomography or magnetic resonance, and by
      the analysis of cerebrospinal fluid.

PMID- 9646014
TI  - Darwin's revolution.

PMID- 9646008
TI  - Clinical pharmacokinetics of vasodilators. Part I.
AB  - Understanding the mechanism of action and the pharmacokinetic properties of
      vasodilatory drugs facilitates optimal use in clinical practice. It should be
      kept in mind that a drug belongs to a class but is a distinct entity, sometimes
      derived from a prototype to achieve a specific effect. The most common
      pharmacokinetic drug improvement is the development of a drug with a half-life
      sufficiently long to allow an adequate once-daily dosage. Developing a controlled
      release preparation can increase the apparent half-life of a drug. Altering the
      molecular structure may also increase the half-life of a prototype drug. Another
      desirable improvement is increasing the specificity of a drug, which may result
      in fewer adverse effects, or more efficacy at the target site. This is especially
      important for vasodilatory drugs which may be administered over decades for the
      treatment of hypertension, which usually does not interfere with subjective well
      being. Compliance is greatly increased with once-daily dosing. Vasodilatory
      agents cause relaxation by either a decrease in cytoplasmic calcium, an increase
      in nitric oxide (NO) or by inhibiting myosin light chain kinase. They are divided
      into 9 classes: calcium antagonists, potassium channel openers, ACE inhibitors,
      angiotensin-II receptor antagonists, alpha-adrenergic and imidazole receptor
      antagonists, beta 1-adrenergic agonist, phosphodiesterase inhibitors, eicosanoids
      and NO donors. Despite chemical differences, the pharmacokinetic properties of
      calcium antagonists are similar. Absorption from the gastrointestinal tract is
      high, with all substances undergoing considerable first-pass metabolism by the
      liver, resulting in low bioavailability and pronounced individual variation in
      pharmacokinetics. Renal impairment has little effect on pharmacokinetics since
      renal elimination of these agents is minimal. Except for the newer drugs of the
      dihydropyridine type, amlodipine, felodipine, isradipine, nilvadipine,
      nisoldipine and nitrendipine, the half-life of calcium antagonists is short.
      Maintaining an effective drug concentration for the remainder of these agents
      requires multiple daily dosing, in some cases even with controlled release
      formulations. However, a coat-core preparation of nifedipine has been developed
      to allow once-daily administration. Adverse effects are directly correlated to
      the potency of the individual calcium antagonists. Treatment with the potassium
      channel opener minoxidil is reserved for patients with moderately severe to
      severe hypertension which is refractory to other treatment. Diazoxide and
      hydralazine are chiefly used to treat severe hypertensive emergencies, primary
      pulmonary and malignant hypertension and in severe preeclampsia. ACE inhibitors
      prevent conversion of angiotensin-I to angiotensin-II and are most effective when
      renin production is increased. Since ACE is identical to kininase-II, which
      inactivates the potent endogenous vasodilator bradykinin, ACE inhibition causes a
      reduction in bradykinin degradation. ACE inhibitors exert cardioprotective and
      cardioreparative effects by preventing and reversing cardiac fibrosis and
      ventricular hypertrophy in animal models. The predominant elimination pathway of
      most ACE inhibitors is via renal excretion. Therefore, renal impairment is
      associated with reduced elimination and a dosage reduction of 25 to 50% is
      recommended in patients with moderate to severe renal impairment. Separating
      angiotensin-II inhibition from bradykinin potentiation has been the goal in
      developing angiotensin-II receptor antagonists. The incidence of adverse effects
      of such an agent, losartan, is comparable to that encountered with placebo
      treatment, and the troublesome cough associated with ACE inhibitors is absent.

PMID- 9646015
TI  - The different faces of science: is genetics a social construct?

PMID- 9646016
TI  - Bare heads against red hats: a portrait of Paracelsus.

PMID- 9646017
TI  - Science--education and culture. Ideas and concepts of German nineteenth century
      scientists.

PMID- 9646018
TI  - Thomas George Hodgkins (1803-92) and the future of research at the Royal
      Institution (London) and the Smithsonian Institution (Washington).

PMID- 9646019
TI  - Biology as technology.
AB  - In this paper we have emphasised the technological dimension of the biosciences,
      especially the biosciences of our time. As a straight forward fact this dimension
      is less controversial than the question of its relevance is. We have argued that
      the existence of this dimension is a consequence of the empirical character of
      the biosciences (as well as of the sciences in general). Knowledge of nature can
      be achieved only if the subject of knowledge is able to gain access to natural
      phenomena, and technological means have become increasingly necessary for
      achieving this. The more that is already known, the greater the technological
      investment required to produce new knowledge. Therefore there is an
      interrelationship between the advancement of knowledge and the amount and
      complexity of the research technology required. It would be short sighted to
      conclude from this observation that human imagination and inventiveness have
      become superfluous. Nevertheless the growing preponderance of technological means
      for progress in science is undeniable. A particularly important insight is that
      this process not only involves a quantitative increase in technology within
      science. Our main hypothesis is that there is a close relationship between the
      type of means used, the type of subject required for performing research, the
      kinds of objects investigated in science, and the nature of the results that are
      generated. We have tried to illustrate this by distinguishing between three
      different types of bioscience: (a) a descriptive type, (b) an experimental type,
      and (c) and an industrial type. Without pretending this provides a universal key
      to the history of the biosciences and to understanding of the way science works
      today, we hope that such a distinction may open up new avenues of thought. We
      hope that this approach will provide us with a more realistic picture of science.
      The propositional view reduces science to its theoretical results, in particular
      to the theories emanating from basic research. Science is seen as a special kind
      of philosophy; its central aim is to provide us with a 'true' view of the world.
      Thus the social problems which result from scientific inquiry and from the
      application of its results seem to be something external to the very essence of
      science and thus only of secondary importance. We believe, therefore, that this
      picture of science is both theoretically unsatisfactory and socially misleading.
      An appropriate account of science cannot ignore the fact that basic research
      represents only a very small part of the science system of our time. It cannot
      neglect the fact that science today is steeped with technology and to a great
      extent also industrialised. And it cannot treat the social problems of science as
      something merely 'external'. To view science as an activity in the sense outlined
      in this paper permits one to integrate these different aspects into one coherent
      and realistic picture. 1. It is obvious that technology plays a crucial role in
      determining the social reality of science. This is mainly because of the high
      costs of contemporary research technology that science can no longer be performed
      by gentleman scientists like Alexander von Humboldt or Charles Darwin, who not
      only financed their own living but the cost of their own research too. Science
      today is a profession, and in many cases it can be performed only in large groups
      or institutions financed by the state or by private companies. At the same time
      this means that it is more and more dependent upon decisions made outside
      science. Scientific activities have assumed the economic form of wage labour. The
      internal structure of science is characterised by a division of labour and
      hierarchical forms of decision making. 2. From a more traditional point this may
      seem to be a development 'external' to science, without any relevance for its
      'essence'. The aim of science, it may be said, is to discover the truth about the
      external world, and the ways of reaching it a

PMID- 9646020
TI  - From the "originary phenomenon" to the "system of pelagic fishery": Johannes
      Muller (1801-1858) and the relation between physiology and philosophy.

PMID- 9646021
TI  - A male mind in a female body: sexology, homosexuality, and the woman question in
      Germany, 1869-1914.

PMID- 9646022
TI  - The naturalist tradition: a natural history.

PMID- 9646023
TI  - Medicine, the body and the botanical metaphor in erotica.

PMID- 9646024
TI  - Biology of liberation: some historical aspects of "proletarian race hygienics".

PMID- 9646025
TI  - Credit and resistance: Eijkman and the transformation of beri-beri into a vitamin
      deficiency disease.

PMID- 9646026
TI  - Gout and quackery; or Banks and the mountebanks.

PMID- 9646027
TI  - Highlights from the annual meeting of the Association for Molecular Pathology.

PMID- 9646028
TI  - Molecular analysis of the p53 gene in pancreatic adenocarcinoma.
AB  - Mutations in the p53 tumor suppressor gene are the most common genetic
      alterations found in human cancer. Most mutations are accompanied by
      stabilization of the protein, which renders the mutations detectable through
      immunohistochemical techniques. The immunoreactivity of p53, however, might not
      correlate with the result of p53 DNA sequencing. In order to explain the
      discrepancy, we studied the p53 expressions, mutations, and changes of the three
      dimensional protein structure of mutant p53 in a series of 61 pancreatic
      adenocarcinoma specimens using immunohistochemistry, polymerase chain reaction
      single strand conformation polymorphism (PCR-SSCP), DNA sequencing, and
      computerized protein modeling. PCR-SSCP followed by DNA sequencing of the p53
      gene showed mutations in 31.2% (19 of 61) of the pancreatic adenocarcinomas.
      Eight of 19 cases showed p53 immunopositivity. These mutations were located on
      the surface of the three-dimensional structure or formed unfolded proteins, which
      were easily recognized by the antibody. Among other mutations in which p53 was
      immunonegative, five cases with deletions and insertion caused frameshift and
      formation of severely truncated p53 protein structures unreactive with the
      antibody used. In three cases with point mutations, the mutant amino acids were
      located in the core of the tightly packed beta sandwich inaccessible to the
      antibody. Three silent mutations were immunonegative, corresponding with the
      absence of amino acid changes. These results strongly suggest that the analysis
      of a computer-generated p53 three-dimensional model based on DNA sequencing data
      can assist in evaluating the significance of p53 immunostaining and mutations for
      clinical applications.

PMID- 9646029
TI  - Detection of tyrosinase mRNA in formalin-fixed, paraffin-embedded archival
      sections of melanoma, using the reverse transcriptase in situ polymerase chain
      reaction.
AB  - Most studies of the reverse transcriptase in situ polymerase chain reaction
      technique have reported results from assessments of cultured cells, frozen
      sections, and cytospin preparations. For application to routine diagnosis, it
      will be necessary to adapt the technique for use with formalin-fixed, paraffin
      embedded tissues, the materials that are generally available. We have evaluated
      the feasibility of such an approach, using surgical pathology archival material
      from 25 UCLA patients: 15 tissues from primary and metastatic melanoma, 7 from
      nonmelanocytic tumors, including cancer of the lung, colon, kidney and skin and a
      thyroid adenoma, and 3 nontumorous tissues. Seven of 15 melanoma tissues gave a
      strong positive signal, 5 gave a weak signal, and 3 were negative. None of the 10
      nonmelanoma tissues gave a positive signal. The specific reaction product was
      mainly located in the cytoplasm. None of the nonmelanocytic tumors or normal
      tissues demonstrated this pattern of cytoplasmic staining. Some nonspecific
      nuclear staining was observed in melanocytic and nonmelanocytic tumors and must
      not be overread as a true positive result. It is possible to detect tyrosinase
      mRNA in formalin-fixed, paraffin-embedded tissue sections of melanoma, but the
      technique remains too demanding for routine application.

PMID- 9646030
TI  - Translocation (X;18) in a biphasic synovial sarcoma with morphologic features of
      neural differentiation.
AB  - The authors report a recurred neoplasm showing distinctive histologic,
      immunophenotypic, and ultrastructural features characteristic of biphasic
      synovial sarcoma with neural differentiation. The features include areas with a
      growth pattern of densely packed spindle cells in irregularly intersecting, broad
      fascicles, diffuse vimentin and HBA 71 immunoreactivity, expression of S-100
      protein, and other neural markers. Moreover, areas with glandular structures and
      cellular expression of cytokeratin and epithelial membrane antigen were noted.
      Additionally, areas of neural-like growth pattern were positive for neuron
      specific enolase, HNK-1, and protein gene product 9.5. Furthermore, cytogenetic
      analysis, two-color interphase fluorescence in situ hybridization, and reverse
      transcription polymerase chain reaction demonstrated the reciprocal translocation
      between chromosomes X and 18 associated with the different subtypes of tumor
      cells. The establishment and characterization of the tumor cell line are
      detailed. This cell line retains the distinct morphologic and genetic
      characteristics of the original biphasic synovial sarcoma with neural
      differentiation.

PMID- 9646031
TI  - Molecular variants of the EWS-WT1 gene fusion in desmoplastic small round cell
      tumor.
AB  - We report two cases of desmoplastic small round cell tumor (DSRCT) with novel
      molecular variants of the specific EWS-WT1 gene fusion. This fusion usually
      encodes a chimeric RNA with an in-frame junction of exon 7 of EWS to exon 8 of
      WT1. In one variant patient, the EWS-WT1 fusion transcript contained an in-frame
      junction of exon 9 of EWS to exon 8 of WT1. Moreover, in this patient the tumor
      arose in the hand, an extremely unusual site for DSRCT. In the second patient, an
      in-frame junction of exon 10 of EWS to exon 8 of WT1 was present. These two cases
      of DSRCT show that the molecular variability in the EWS breakpoint observed in
      the EWS-FLI1 fusion of Ewing's sarcoma can occur in DSRCT as well. This type of
      heterogeneity is relevant to the interpretation of molecular diagnostic assays
      and could also affect the functional properties of the encoded chimeric
      transcription factors.

PMID- 9646032
TI  - Molecular diagnosis of Ewing tumors: improved detection of EWS-FLI-1 and EWS-ERG
      chimeric transcripts and rapid determination of exon combinations.
AB  - Most Ewing tumors (ET), including Ewing sarcomas, peripheral primitive
      neuroectodermal tumors (PNET), and Askin's tumors, can be defined according to
      the specific chromosomal translocations t(11;22)(q24;q12) (EWS-FLI-1) or
      t(21;22)(q21;q12) (EWS-ERG). Detection of the chimeric RNA transcripts by reverse
      transcriptase-polymerase chain reaction (RT-PCR) has greatly facilitated the
      diagnosis of ET. Because of variable chromosomal breakpoint locations, however,
      the EWS gene fusions with FLI-1 and ERG genes are highly heterogenous, resulting
      in different sizes of the amplification products. To improve the diagnostic
      usefulness of the RT-PCR assay, we have developed an assay to detect chimeric
      mRNA transcripts by nested RT-PCR, followed by digestion of the PCR fragments
      with three different restriction endonucleases. This allows confirmation of the
      specificity of the PCR product and provides a rapid method to determine the
      combination of exons present in a transcript. In the 12 Ewing tumors tested, five
      different exon combinations were detected. In nine repeat biopsies of four
      patients, the case-specific translocation remained unchanged. One additional
      central PNET had no ET-specific translocation. In conclusion, the suggested
      combination of RT-PCR and restriction analysis of the PCR products allows a rapid
      and specific determination of ET-specific translocations.

PMID- 9646033
TI  - Neuroendocrine differentiation in Ewing's sarcomas and primitive neuroectodermal
      tumors revealed by reverse transcriptase-polymerase chain reaction of
      chromogranin mRNA.
AB  - Ewing's sarcomas (ESs), primitive neuroectodermal tumors (PNETs), and
      neuroblastomas (NBs) are closely related neoplasms supposedly derived from the
      neural crest and belonging to the family of the small blue round cell tumors of
      infancy and childhood. We investigated the expression of the neuroendocrine and
      neuroectodermal markers chromogranin A (CgA) and secretogranin II (SgII) in ESs,
      PNETs, and NBs, both in primitive tumors (five, nine, and four cases,
      respectively) and in established cell lines (three ES and two PNET cell lines).
      Different technical approaches, namely immunohistochemistry, Northern blot
      analysis, and reverse transcriptase-polymerase chain reaction (RT-PCR) were used
      in parallel. Chromogranin A and secretogranin II production was constantly
      detectable in NBs by all procedures. CgA mRNA was detectable in most ESs and
      PNETs only by RT-PCR, whereas SgII mRNA was detectable in some ESs and PNETs by
      Northern blot analysis and in all tumors by RT-PCR. CgA and SgII proteins were
      never detectable by immunohistochemistry in ESs and PNETs. We conclude that
      neuroendocrine differentiation is shared by all three tumor entities, being more
      overt in NBs and rudimentary in ESs and PNETs; traces of chromogranin mRNA are
      detectable only by a highly sensitive RT-PCR procedure.

PMID- 9646034
TI  - Expression of macrophage migration inhibitory factor in the human prostate.
AB  - The expression of macrophage migration inhibitory factor (MIF) in prostate tissue
      was investigated by immunohistochemistry (IHC), enzyme-linked immunosorbent assay
      (ELISA), and Northern blot analysis using a prostate tissue bank. MIF expression
      was examined in each of the following established prostate tissue categories:
      prepubertal, pubertal, adult normal, benign hyperplastic (BPH), focal carcinoma
      within the prostate, and metastatic prostate cancer. IHC showed that all samples
      tested were positive for MIF protein, which localized to the glandular epithelial
      cells with no apparent staining of stroma. The most intense staining was observed
      in the metastatic prostatic adenocarcinoma and the human prostatic adenocarcinoma
      cell line LNCaP. Using quantitative ELISA, MIF expression was found to be at
      least three times higher in metastatic adenocarcinoma than in normal, BPH, or
      focal carcinoma in the adult prostate. This study is the first to report that
      prostate glandular epithelial cells express MIF. The exact role of MIF in
      prostate development and disease progression requires further study.

PMID- 9646035
TI  - p53 mutations in chondrosarcoma.
AB  - Chondrosarcoma is a primary bone tumor that has several different grades and
      variants. We evaluated 48 chondrosarcomas for p53 overexpression and p53
      mutations. p53 expression was evaluated with immunohistochemistry using
      monoclonal antibodies PAb421, PAb1801, and PAb240. p53 mutations were identified
      with single-strand conformational polymorphism (SSCP) and DNA sequencing in
      selected cases. Immunohistochemistry revealed nuclear staining with PAb421 and
      PAb1801 in the spindle cell portion of one dedifferentiated chondrosarcoma. SSCP
      analysis was abnormal only in the case with positive immunostaining and localized
      the mutation to exons 7 and 8. DNA sequence analysis identified a point mutation
      of G to C in codon 276, resulting in an amino acid substitution of proline for
      alanine. This point mutation has been reported previously in other tumors but not
      in chondrosarcoma. Assimilation of our results with previous studies suggests
      that p53 mutations are present in a minority of chondrosarcomas but when present,
      are in higher grade chondrosarcomas and their variants.

PMID- 9646036
TI  - Frequent loss of heterozygosity at chromosome 13q12-13 with BRCA2 markers in
      sporadic male breast cancer.
AB  - Molecular genetic analysis indicates that the BRCA2 gene plays an important role
      in familial male breast cancer. To determine a possible involvement of this tumor
      suppressor gene in sporadic male breast cancer, we examined 30 sporadic male
      breast carcinomas for loss of heterozygosity (LOH) at two loci on chromosome
      13q12-13, a region that spans the BRCA2 locus. Sixteen of 24 (67%) informative
      cases showed LOH in at least one marker on chromosome 13q12-13. The affected
      cases included both invasive ductal carcinomas and other types of invasive breast
      carcinoma and were detected preferentially in patients who were 50 years or
      older, in patients with lymph node metastasis, and in progesterone receptor
      negative cases. We report, for the first time, a high frequency of LOH at
      chromosome 13q12-13 in sporadic male breast cancer and its association with
      factors indicating a poor prognosis for this tumor (e.g., lymph node metastasis
      and negative progesterone receptor status). These findings suggest an important
      role for BRCA2 in the development and progression of sporadic male breast cancer.

PMID- 9646037
TI  - Detection of molecular changes in primary intraocular lymphoma by microdissection
      and polymerase chain reaction.

PMID- 9646038
TI  - Children's health and the environment: a new agenda for prevention research.
AB  - Patterns of illness in American children have changed dramatically in this
      century. The ancient infectious diseases have largely been controlled. The major
      diseases confronting children now are chronic and disabling conditions termed the
      "new pediatric morbidity"--asthma mortality has doubled; leukemia and brain
      cancer have increased in incidence; neurodevelopmental dysfunction is widespread;
      hypospadias incidence has doubled. Chemical toxicants in the environment as well
      as poverty, racism, and inequitable access to medical care are factors known and
      suspected to contribute to causation of these pediatric diseases. Children are at
      risk of exposure to over 15,000 high-production-volume synthetic chemicals,
      nearly all of them developed in the past 50 years. These chemicals are used
      widely in consumer products and are dispersed in the environment. More than half
      are untested for toxicity. Children appear uniquely vulnerable to chemical
      toxicants because of their disproportionately heavy exposures and their inherent
      biological susceptibility. To prevent disease of environmental origin in
      America's children, the Children's Environmental Health Network (CEHN) calls for
      a comprehensive, national, child-centered agenda. This agenda must recognize
      children's vulnerabilities to environmental toxicants. It must encompass a) a new
      prevention-oriented research focus; b) a new child-centered paradigm for health
      risk assessment and policy formulation; and c) a campaign to educate the public,
      health professionals, and policy makers that environmental disease is caused by
      preventable exposures and is therefore avoidable. To anchor the agenda, CEHN
      calls for long-term, stable investment and for creation of a national network of
      pediatric environmental health research and prevention centers.

PMID- 9646039
TI  - Programming for responsiveness to environmental antigens that trigger allergic
      respiratory disease in adulthood is initiated during the perinatal period.
AB  - Allergy to airborne environmental antigens (allergens) is a major cause of asthma
      in children and adults. This review argues that the development of allergen
      specific immunologic memory of the type that predisposes to allergy development
      is the end result of a T-cell selection process operative during infancy, which
      is triggered via encounters between the immature immune system and incoming
      airborne allergens from the environment. In normal individuals this process leads
      to the development of allergen-specific T-memory cells that secure the T helper
      (Th)-1 pattern of cytokines, which actively suppress the growth of their allergy
      inducing Th-2 cytokine-secreting counterparts. However, these protective allergen
      reactive Th-1 memory cells fail to develop in some individuals, permitting the
      subsequent proliferation of allergen-specific Th-2 cells that can trigger
      allergic reactions. Recent evidence suggests that genetic predisposition to
      allergy may be due in part to hyperactivity of control mechanisms operative in
      utero and which normally protect the fetoplacental unit against the toxic effect
      of Th-1 cytokines.

PMID- 9646040
TI  - Genetic predispositions and childhood cancer.
AB  - This article provides an overview of the problem of genetic susceptibility to
      childhood cancer with a particular emphasis on problems with ascertaining
      inherited cancer risk and the role of tumor-suppressor gene mutations in cancer
      predispositions. The association between neurofibromatosis type 1 and childhood
      leukemia is used to illustrate some of the issues faced by molecular biologists
      and genetic epidemiologists in identifying and analyzing at-risk individuals. The
      problem of incomplete penetrance in cancer susceptibility is presented and
      potential models are discussed. The article concludes with a number of tentative
      conclusions from existing data and speculations for future studies.

PMID- 9646041
TI  - Developmental neurotoxicology of endocrine disruptors and pesticides:
      identification of information gaps and research needs.
AB  - There is increasing evidence that some environmental chemicals can interrupt
      neurodevelopmental processes during critical periods of development, resulting in
      effects on sensory, motor, and cognitive function. It is now generally accepted
      that developing organisms are differentially sensitive to chemical exposure
      because of toxicokinetic and/or toxicodynamic factors. Regulatory mechanisms have
      been implemented to protect humans from over- or inappropriate exposures to
      environmental chemicals. Current regulatory practices, however, may be
      insufficient because of the possibility that some environmental chemicals
      interfere with endocrine function at key periods of neurodevelopment. In
      addition, a recent National Research Council (NRC) report on pesticide
      contamination in the diets of infants and children concluded that current
      regulatory practices may not sufficiently protect infants and children from the
      risk of pesticide exposure. The NRC report indicates that regulatory agencies
      might underestimate the actual exposure of infants and children to pesticides and
      rely too heavily on data from adults in the risk assessment of pesticides.
      Consideration of endocrine-disrupting chemicals and the differential
      susceptibility of infants and children has led to identification of a number of
      information gaps and research needs that should be addressed in order to improve
      future risk assessments for these chemicals.

PMID- 9646042
TI  - Biomarkers in pediatric environmental health: a cross-cutting issue.
AB  - It is not yet known the extent to which the environment adversely affects the
      health of the developing individual. Difficulties in this determination are the
      problems of a) the assessment of exposure, b) the long latency of many diseases
      induced by the environment, c) the number of confounding exposures, and d) the
      extrapolation of animal models to critical stages of human development.
      Biomarkers have the potential to be quantitative dosimeters of exposure and
      biologic effective dose, as well as early warning signals of biologic effect.
      Biomarkers may document interindividual susceptibilities, as well as defining
      critical windows of exposure. To be useful, biomarkers need to be validated in
      terms of their specificity and sensitivity. Biomarkers are useful across all
      disciplines including asthma and respiratory problems, developmental
      neurotoxicity, childhood cancer, and endocrine disruptors. Biomarkers have not
      been developed nor used widely in pediatric environmental health. Research by our
      group and others has documented the validity of biomarkers in pediatric
      environmental health. Advances in the field of biomarkers may have important
      implications for the detection, prevention, and treatment of environmentally
      induced diseases in children. Ongoing validation of promising biomarkers should
      be a research priority.

PMID- 9646043
TI  - Genes and the environment: their impact on children's health.
AB  - Because the human population is biologically diverse and genetically
      heterogeneous, it is not surprising that differences in susceptibility to disease
      among individuals with or without exposure to environmental agents exist.
      Individuals vary greatly in their susceptibility to disease. This is true of
      adults and children. The etiologies of many diseases of childhood are due to a
      combination of factors, including genetic susceptibility and environmental
      exposures during vulnerable periods of development. Genes regulate cellular
      growth and development, DNA replication and repair, the metabolism of endogenous
      agents in the body, and the metabolism and excretion of exogenous agents that the
      body comes in contact with in the environment. This regulation varies over the
      life span, contributing to the cellular consequences of the environmental
      exposures. This paper summarizes the contributions of genetics in understanding
      the etiology of environmentally induced diseases in children. The use of
      biomarkers of genetic susceptibility in the study of these diseases will be
      discussed. Future research needs for expanding our knowledge of the interactions
      between genetic and environmental components of childhood diseases will be
      presented.

PMID- 9646044
TI  - Relationship between ambient air pollution and DNA damage in Polish mothers and
      newborns.
AB  - Industrialized regions in Poland are characterized by high ambient pollution,
      including polycyclic aromatic hydrocarbons (PAHs) from coal burning for industry
      and home heating. In experimental bioassays, certain PAHs are transplacental
      carcinogens and developmental toxicants. Biologic markers can facilitate
      evaluation of effects of environmental PAHs on the developing infant. We measured
      the amount of PAHs bound to DNA (PAH-DNA adducts) in maternal and umbilical white
      blood cells. The cohort consisted of 70 mothers and newborns from Krakow, Poland,
      an industrialized city with elevated air pollution. Modulation of adduct levels
      by genotypes previously linked to risk of lung cancer, specifically glutathione S
      transferase MI (GSTM1) and cytochrome P4501A1 (CYP1A1) Msp restriction fragment
      length polymorphism (RFLP), was also investigated. There was a dose-related
      increase in maternal and newborn adduct levels with ambient pollution at the
      women's place of residence among subjects who were not employed away from home (p
      < or = 0.05). Maternal smoking (active and passive) significantly increased
      maternal (p < or = 0.01) but not newborn adduct levels. Neither CYP1A1 Msp nor
      GSTM1 polymorphisms was associated with maternal adducts. However, adducts were
      significantly higher in newborns heterozygous or homozygous for the CYP1A1 Msp
      RFLP compared to newborns without the RFLP (p = 0.04). Results indicate that PAH
      induced DNA damage in mothers and newborns is increased by ambient air pollution.
      In the fetus, this damage appears to be enhanced by the CYP1A1 Mspl polymorphism.

PMID- 9646045
TI  - Approaches to environmental exposure assessment in children.
AB  - An improved understanding of the contribution made by environmental exposures to
      disease burden in children is essential, given current increasing rates of
      childhood illnesses such asthma and cancer. Children must be routinely included
      in environmental research. Exposure assessment, both external (e.g., air, water)
      and internal dose (e.g., biomarkers), is an integral component of such research.
      Biomarker measurement has some advantages that are unique in children. These
      include assessment of potentially increased absorption because of behaviors that
      differ from adults (i.e., hand-to-mouth activity); metabolite measurement, which
      can help identify age-related susceptibility differences; and improved assessment
      of dermal exposure, an important exposure route in children. Environmental
      exposure assessment in children will require adaption of techniques that are
      currently applied in adult studies as well as development of tools and validation
      of strategies that are unique for children. Designs that focus on parent-child
      study units provide adult comparison data and allow the parent to assist with
      more complex study designs. Use of equipment that is sized appropriately for
      children, such as small air pumps and badge monitors, is also important. When
      biomarkers are used, biologic specimens that can be obtained noninvasively are
      preferable. Although the current need is primarily for small focused studies to
      address specific questions and optimize research tools, the future will require
      establishment of large prospective cohorts. Urban children are an important study
      cohort because of relatively high morbidity observed in the urban environment.
      Finally, examples of completed or possible future studies utilizing these
      techniques are discussed for specific exposures such as benzene, environmental
      tobacco smoke, aflatoxin, volatile organic compounds, and polycyclic aromatic
      hydrocarbons.

PMID- 9646046
TI  - A partnership study of PCBs and the health of Mohawk youth: lessons from our past
      and guidelines for our future.
AB  - This paper describes a research partnership between the people of Akwesasne and
      researchers from the State University of New York at Albany for the study of
      polychlorinated biphenyls and the health of Mohawk youth. The study is
      distinctive because its goals have been set by the scientists and the community
      members and is being conducted jointly by these groups. The research partnership
      recognizes the history of relationships between native and nonnative peoples,
      particularly scientists, and seeks not only to fulfill certain scientific goals
      but to further community ones as well. The relationship is based on three
      principles: mutual respect, mutual equity, and mutual empowerment. These
      principles guided every aspect of the research process. The project goals were
      determined jointly to maximize data quality and minimize the intrusion of
      research activities into the lives of community members. Data collection is
      performed by research assistants who received extensive and ongoing training in
      data collection methods, and who are members of the community. Feedback
      procedures were designed by community members and scientists jointly to maximize
      understanding. Feedback regarding individuals' pollutant levels and assessments
      of growth and development are provided to each individual. Information about
      community pollutant levels are provided to the community. Hypothesis testing is
      carried out by research scientists, and the results presented first at a
      community meeting. Research conducted in this way--as a partnership--requires
      more communication, discussion, and travel, but the result is mutual satisfaction
      and growth.

PMID- 9646047
TI  - Prenatal methylmercury exposure and children: neurologic, developmental, and
      behavioral research.
AB  - Mercury is present in the earth's crust and is methylated by bacteria in aquatic
      environments to methylmercury (MeHg). It is then concentrated by the food chain
      so predatory fish and sea mammals have the highest levels. Thus, consuming
      seafood leads to exposure. MeHg readily crosses the placenta and the blood-brain
      barrier and is neurotoxic. The developing fetal nervous system is especially
      sensitive to its effects. Prenatal poisoning with high dose MeHg causes mental
      retardation and cerebral palsy. Lower level exposures from maternal consumption
      of a fish diet have not been consistently associated with adverse
      neurodevelopmental outcomes. However, most studies have considerable uncertainty
      associated with their results. Two large controlled longitudinal studies of
      populations consuming seafood are underway that are likely to determine if any
      adverse effects can be identified. No adverse associations have been found in the
      Seychelles, where exposure is mainly from fish consumption. In the Faroe Islands
      where exposure is primarily from consumption of whale meat and not fish, adverse
      associations have been reported. The Seychelles population consumes large amounts
      of marine fish containing MeHg concentrations similar to commercial fish in the
      United States. Current evidence does not support the hypothesis that consumption
      of such fish during pregnancy places the fetus at increased neurodevelopmental
      risk.

PMID- 9646049
TI  - Linking research and policy to ensure children's environmental health.
AB  - The U.S. Environmental Protection Agency (U.S. EPA) has made protecting
      children's environmental health its highest priority. Data on how and when
      children may be at risk are vital for accomplishing this goal. Recent examples of
      the link between research and policy include U.S. EPA actions to carry out the
      recommendations of the National Academy of Sciences on pesticides in children's
      food, reduce and prevent childhood lead poisoning, and revise national ambient
      air quality standards for ozone and particulate matter. Today, the Food Quality
      Protection Act (FQPA), which makes protecting children from pesticide residues in
      food a national priority, is contributing to the growing need for data for
      decision making. Further impetus comes from provisions in the FQPA and 1996 Safe
      Drinking Water Act Amendments for establishing a screening and testing program
      for potential risks from endocrine disruptors. Another factor is the analysis
      that will be required under President William J. Clinton's executive order
      directing all federal agencies, for the first time, to reduce environmental
      health and safety risks to children. Success of the U.S. international commitment
      to protect children is directly tied to the strength and availability of
      environmental data. To meet such challenges, the U.S. EPA is revising key science
      policies, expanding research opportunities, and adding to the public's right-to
      know tools. In this dynamic climate, there are growing opportunities for the
      research community to play a greater role in helping ensure the well-being of
      children living today and in generations to come.

PMID- 9646048
TI  - Environmental health sciences education--a tool for achieving environmental
      equity and protecting children.
AB  - Children are highly susceptible to deleterious effects of environmental toxins.
      Those who live in underserved communities may be particularly at risk because
      environmental pollution has been found to be disproportionately distributed among
      communities. Mounting evidence suggests that asthma rates are rising and that
      this disease can be caused or aggravated by air pollution. Although ambient air
      quality has generally improved, these improvements have not reached minority
      communities in equal proportions. This and other data has fueled the concept of
      environmental justice or environmental equity, which has led to community
      activism and government actions. One possible example of environmental inequity
      and its consequences is the Hunt's Point community, in the South Bronx, New York.
      This community experiences a high pollution burden with the siting of facilities
      that emit hazardous wastes into the air. Our approach to this problem has been
      the formation of mechanisms for bidirectional communication between community
      residents, government entities, and academic institutions such as Mount Sinai
      Medical Center. As a result of this experience, we believe that the key to
      achieving environmental health, especially in communities of color where many
      children are at risk, is to empower residents to take charge of their environment
      by providing relevant educational opportunities. Strategies for environmental
      health education include multitiered training approaches that include community
      residents, parent education, direct children education, and community education
      through professional counselors and train-the-trainer approaches. We propose that
      academic researchers must use community residents not just as subjects of our
      studies, but to increase our mutual understanding of environmental health,
      resulting in active participation of community members in research design, data
      collection, analysis, and dissemination of results in order to make intervention
      strategies more effective.

PMID- 9646050
TI  - The U.S. EPA Conference on Preventable Causes of Cancer in Children: a research
      agenda.
AB  - On 15-16 September 1997, the U.S. Environmental Protection Agency sponsored the
      Conference on Preventable Causes of Cancer in Children. The conference was
      convened to examine rising trends in reported incidence of childhood cancer and
      the association of these trends with environmental exposures. This paper
      summarizes recommendations for future research offered by participants. These
      recommendations included more collaborative research integrating epidemiology,
      molecular biology, toxicology, and risk assessment; the development of better
      protocols for toxicologic testing including carcinogenicity using young animals;
      and research focused on specific periods of development during which
      susceptibility to environmental agents may be enhanced. Also recommended was
      enhanced use and development of molecular biomarkers for identification of
      susceptible populations, and documentation of exposures and effects in
      epidemiologic and toxicologic studies. Although toxicologic testing is considered
      essential to determine the effects of potential carcinogens on biological
      organisms, participants emphasized the need to link these findings with
      epidemiologic and exposure assessment research.

PMID- 9646051
TI  - Chemicals and children's environment: what we don't know about risks.
AB  - Although we know that certain types of childhood cancers are increasing, we do
      not know why. With few exceptions, we know little about the role of environmental
      carcinogens in childhood cancer. Generally, we have adequate information to
      screen chemicals for potential hazard for only certain categories of chemicals-
      drugs, food additives, and pesticides. The U.S. Environmental Protection Agency
      (U.S. EPA) is implementing the 1996 Food Quality Protection Act, which provides
      added protections against pesticide risks, especially for children. But the
      situation is quite different for many industrial chemicals. We lack even basic
      toxicity data for a majority of the U.S. EPA's list of approximately 3000
      nonpolymeric high-production-volume industrial chemicals being produced in the
      United States each year that are found in consumer products and the workplace. We
      know even less about the remaining 70,000 chemicals on the U.S. EPA inventory.
      The U.S. EPA has initiatives underway to address the risks posed by some of these
      commercial chemicals, including efforts to reduce risks posed by indoor air
      pollutants and household products. These initiatives specifically address
      children's risks. We are supporting toxicity screening of high-volume industrial
      chemicals on a cooperative international basis through the Organisation for
      Economic Co-operation and Development. Until more information is available, it is
      difficult to assess the possible role of these chemicals in childhood cancer and
      to take steps to reduce exposure to children.

PMID- 9646052
TI  - Methodologic approaches to studying environmental factors in childhood cancer.
AB  - Little is known about environmental causes of childhood cancer. This is probably
      due to the relative rarity of cancer in children. In the United States, cancer
      incidence in adults is over 20 times greater than cancer incidence in children.
      The situation is compounded by the fact that two groups of cancers, leukemias and
      brain and spinal tumors, account for half of all childhood cancers. The rarity of
      childhood cancer renders the conduct of most cohort studies infeasible. The
      majority of studies assessing potential environmental risk factors for childhood
      cancers have been case-control studies, which are highly efficient for studying
      rare diseases. Case-control studies of childhood cancers have been greatly
      facilitated by using cooperative clinical trial groups for case identification.
      The national studies that have emerged utilize random-digit telephone dialing and
      telephone interviewing as feasible and economic means of identifying and
      interviewing controls. Other approaches such as descriptive epidemiology,
      ecologic studies, and studies of cancer clusters have proven to be disappointing
      in elucidating environmental causes of childhood cancer. Descriptive and ecologic
      studies provide no information on specific exposures of study subjects; rather,
      they use population levels as surrogates for individual exposure. Studies of
      cancer clusters have also proven to be disappointing. Although there are numerous
      difficulties in conducting research on the causes of childhood cancer, these
      difficulties can be remedied by using carefully designed and conducted studies.
      It should be remembered that the epidemiologic approach is probably the most
      likely research venue for uncovering environmental causes of childhood cancer.

PMID- 9646053
TI  - Results from an international case-control study of childhood brain tumors: the
      role of prenatal vitamin supplementation.
AB  - An international case-control study of primary pediatric brain tumors included
      interviews with mothers of cases diagnosed from 1976 to 1994 and mothers of
      population controls. Data are available on maternal vitamin use during pregnancy
      for 1051 cases and 1919 controls from eight geographic areas in North America,
      Europe, and Israel. Although risk estimates varied by study center, combined
      results suggest that maternal supplementation for two trimesters may decrease
      risk of brain tumor (odds ratio [OR] 0.7, 95% confidence interval [CI] 0.5-0.9),
      with a trend of less risk with longer duration of use (p trend = 0.0007). The
      greatest risk reduction was among children diagnosed under 5 years of age whose
      mothers used supplements during all three trimesters (OR 0.5, CI 0.3-0.8). This
      effect did not vary by histology and was seen for supplementation during
      pregnancy rather than during the month before pregnancy or while breast feeding.
      These findings are largely driven by data from the United States, where most
      mothers took vitamins. The proportion of control mothers who took vitamins during
      pregnancy varied tremendously: from 3% in Israel and France, 21% in Italy, 33% in
      Canada, 52% in Spain and 86 to 92% at the three U.S. centers. The composition of
      the various multivitamin compounds taken also varied: the daily dose of vitamin C
      ranged from 0 to 600 mg, vitamin E ranged from 0 to 70 mg, vitamin A ranged from
      0 to 30,000 IU, and folate ranged from 0 to 2000 micrograms. Mothers also took
      individual micronutrient supplements (e.g., vitamin C tablets), but most mothers
      who took these also took multivitamins, making it impossible to determine
      potential independent effects of these micronutrients.

PMID- 9646054
TI  - Pesticides and childhood cancer.
AB  - Children are exposed to potentially carcinogenic pesticides from use in homes,
      schools, other buildings, lawns and gardens, through food and contaminated
      drinking water, from agricultural application drift, overspray, or off-gassing,
      and from carry-home exposure of parents occupationally exposed to pesticides.
      Parental exposure during the child's gestation or even preconception may also be
      important. Malignancies linked to pesticides in case reports or case-control
      studies include leukemia, neuroblastoma, Wilms' tumor, soft-tissue sarcoma,
      Ewing's sarcoma, non-Hodgkin's lymphoma, and cancers of the brain, colorectum,
      and testes. Although these studies have been limited by nonspecific pesticide
      exposure information, small numbers of exposed subjects, and the potential for
      case-response bias, it is noteworthy that many of the reported increased risks
      are of greater magnitude than those observed in studies of pesticide-exposed
      adults, suggesting that children may be particularly sensitive to the
      carcinogenic effects of pesticides. Future research should include improved
      exposure assessment, evaluation of risk by age at exposure, and investigation of
      possible genetic-environment interactions. There is potential to prevent at least
      some childhood cancer by reducing or eliminating pesticide exposure.

PMID- 9646055
TI  - Parental occupational exposures and risk of childhood cancer.
AB  - Occupational exposures of parents might be related to cancer in their offspring.
      Forty-eight published studies on this topic have reported relative risks for over
      1000 specific occupation/cancer combinations. Virtually all of the studies
      employed the case-control design. Occupations and exposures of fathers were
      investigated much more frequently than those of the mother. Information about
      parental occupations was derived through interviews or from birth certificates
      and other administrative records. Specific exposures were typically estimated by
      industrial hygienists or were self-reported. The studies have several limitations
      related to the quality of the exposure assessment, small numbers of exposed
      cases, multiple comparisons, and possible bias toward the reporting of positive
      results. Despite these limitations, they provide evidence that certain parental
      exposures may be harmful to children and deserve further study. The strongest
      evidence is for childhood leukemia and paternal exposure to solvents, paints, and
      employment in motor vehicle-related occupations; and childhood nervous system
      cancers and paternal exposure to paints. To more clearly evaluate the importance
      of these and other exposures in future investigations, we need improvements in
      four areas: a) more careful attention must be paid to maternal exposures; b)
      studies should employ more sophisticated exposure assessment techniques; c)
      careful attention must be paid to the postulated mechanism, timing, and route of
      exposure; and d) if postnatal exposures are evaluated, studies should provide
      evidence that the exposure is actually transferred from the workplace to the
      child's environment.

PMID- 9646056
TI  - Tissue injury by reactive oxygen species and the protective effects of
      flavonoids.
AB  - Reactive oxygen species contribute decisively to a great variety of diseases.
      Flavonoids are benzo-gamma-pyrone derivatives of plant origin found in various
      fruits and vegetables but also in tea and in red wine. Some of the flavonoids,
      such as quercetin and silibinin, can effectively protect cells and tissues
      against the deleterious effects of reactive oxygen species. Their antioxidant
      activity results from scavenging of free radicals and other oxidizing
      intermediates, from the chelation of iron or copper ions and from inhibition of
      oxidases. For their free radical scavenging properties, scavenging of lipid- and
      protein-derived radicals is presumably of special importance. A non-radical
      reactive oxygen species effectively trapped by flavonoids is hypochlorous acid.
      In general, the antioxidative properties of flavonoids are favoured by a high
      degree of OH substitution. On the other hand, inhibition of enzymatic functions
      other than oxidases, e.g., inhibition of lipoxygenase and thus prevention of the
      formation of leukotrienes, may also participate in the cell and tissue protective
      properties of flavonoids.

PMID- 9646057
TI  - YM022, a highly potent and selective CCKB antagonist inhibiting gastric acid
      secretion in the rat, the cat and isolated rabbit glands.
AB  - We investigated the effects of the novel CCKB/gastrin antagonist YM022 on gastric
      acid secretion in vivo and in vitro, compared to CI-988 and L365,260 as reference
      antagonists. In the anaesthetized rat, pentagastrin-induced stimulation of
      gastric acid secretion was dose-dependently and up to 100% inhibited by i.v.
      administration of YM022 with an ID50 of 0.009 +/- 0.0006 mumol/kg h in comparison
      to 0.6 +/- 0.03 and 3.40 +/- 0.05 mumol/kg h for CI-988 and L-365,260,
      respectively. In the gastric fistula cat, i.v. administration of YM022 produced a
      similar inhibitory effect with an ID50 of 0.02 mumol/kg in comparison to 1.6 and
      2.5 mumol/kg for CI-988 and L-365,260, respectively. Furthermore, bolus injection
      of 0.6 mumol/kg YM022 produced 100% inhibition within 30 min and 85% inhibition
      was still observed after 3 h. In the isolated rabbit gastric glands, CCK8
      stimulated 14C-aminopyrine uptake was inhibited according to the following rank
      order of potency: YM022 (IC50 = 0.0012 microM) > > CI-988 (IC50 = 0.2 microM) > >
      L365,260 (IC50 = 2.8 microM). Unlike with L365,260, no influence of CI-988 and
      YM022 on histamine-stimulated acid output was shown in this study. Thus, YM022 is
      a highly potent and selective gastric CCKB/gastrin receptor antagonist and has a
      long-lasting inhibitory effect on gastric acid secretion.

PMID- 9646058
TI  - Physical activity, skeletal muscle beta-adrenoceptor changes and oxidative
      metabolism in experimental chronic heart failure.
AB  - In chronic heart failure (CHF), changes in sympathetic nervous activity and
      skeletal muscle metabolism contribute to a limitation in the capacity for
      exercise. The aim of this study was to investigate the potential relationships
      between physical deconditioning, skeletal muscle beta-adrenoceptor (beta-AR)
      characteristics and muscle metabolic changes in rats with coronary ligation
      induced experimental CHF. Muscle beta-AR and norepinephrine levels were assessed
      in rats with CHF that had been treated with propranolol at 28 mg/kg/day and
      compared with rats with CHF that had not been treated and those that had
      undergone sham operations. The soleus muscle was investigated because of its
      predominantly oxidative fibre-type composition. Measurements of spontaneous
      locomotion activity were carried out using telemetry. After 85 days, muscle
      energetic phosphate levels were assessed using 31P-magnetic resonance
      spectroscopy. The phosphocreatine resynthesis rate was decreased in the untreated
      CHF rats (15 +/- 3 vs 33 +/- 5 mmol L-1 min-1 in the sham-operated rats, p <
      0.05), but this had been partially reversed in the rats given propranolol (22 +/-
      3 mmol L-1 min-1, non-significant (NS) when compared with the sham-operated
      rats). Spontaneous activity did not differ among the three groups of animals.
      Soleus beta-adrenoceptor density was decreased in rats with CHF (8.8 +/- 3.0
      fM/mg of protein vs 22.0 +/- 7.0 fM/mg of protein in the sham-operated rats, p <
      0.05) and normalized in the propranolol-treated rats (31.9 +/- 7.0 fM/mg of
      protein, NS vs the sham-operated rats; p < 0.05 vs the untreated rats with CHF).
      Unchanged spontaneous activity in the rats with CHF suggests that physical
      deconditioning could not account for the muscle metabolic changes. Changes in
      skeletal muscle energy metabolism were accompanied by changes in beta-AR density,
      occurring in typically oxidative beta-AR-rich muscles, reversible after beta
      blocker therapy and therefore suggestive of beta-AR downregulation.

PMID- 9646059
TI  - Beneficial hemodynamic effects of nicorandil in a canine model of acute
      congestive heart failure: comparison with nitroglycerin and cromakalim.
AB  - Comparative hemodynamic effects of nicorandil (NCR), nitroglycerin (NTG) and
      cromakalim (CRM) were examined in a canine model of acute congestive heart
      failure (CHF). CHF was produced by injections of saponin into coronary arteries
      of anesthetized dogs followed by volume loading and continuous i.v. infusion of
      methoxamine. After the treatment, aortic blood flow (AoF), left ventricular dP/dt
      and myocardial segment shortening (SS) markedly decreased, while the left
      ventricular end-diastolic pressure (LVEDP), the right atrial pressure (RAP) and
      the systemic vascular resistance (SVR) increased. NCR (n = 6), NTG (n = 6) and
      CRM (n = 8), which were administered i.v. after production of CHF, caused a
      comparable reduction in LVEDP. NCR and CRM profoundly increased AoF and SS but
      NTG did only slightly. On the other hand, NTG and NCR but not CRM significantly
      reduced RAP. Intracoronary NCR (n = 8) exerted no or similar effects on SS as
      well as systemic hemodynamic indices to those observed with i.v. NCR despite
      distinct coronary vasodilation. These results indicate that NCR may exert
      beneficial hemodynamic effects in an experimental CHF mainly due to lessening
      both afterload and preload rather than the coronary vasodilating effect.

PMID- 9646060
TI  - Inhibitory effects of tacrine and physostigmine on catecholamine secretion and
      membrane currents in guinea-pig adrenal chromaffin cells.
AB  - The effects of tacrine and physostigmine on catecholamine secretion induced by
      veratridine and high K+, and on voltage-dependent Na+ and Ca2+ currents, were
      investigated in guinea-pig adrenal chromaffin cells. In perfused adrenal glands,
      tacrine (100 microM) caused an inhibition of veratridine-induced catecholamine
      secretion, but physostigmine (100 microM) did not. In dispersed cells, both
      tacrine (1 microM-1 mM) and physostigmine (1 microM-1 mM) decreased catecholamine
      secretion induced by veratridine in a dose-dependent manner. The inhibitory
      effect of tacrine was much greater than that of physostigmine. Tacrine alone at a
      high concentration (such as 1 mM) caused a substantial increase in catecholamine
      secretion by itself and completely abolished the veratridine-induced secretory
      response in dispersed cells. High-concentration physostigmine showed a similar
      effect, but to a much lesser extent. The high K+ (46.2 mM)-evoked catecholamine
      secretion from dispersed cells was not affected by tacrine (1-100 microM) or
      physostigmine (1 microM-1 mM). In fura-2 loaded cells, tacrine (100 microM)
      almost abolished [Ca2+]i rise induced by veratridine, but only slightly reduced
      that evoked by high K+. In voltage-clamped cells, tacrine (300 microM) depressed
      the voltage-dependent Na+ and Ca2+ current by about 93% and 69%, and
      physostigmine (300 microM) depressed them by about 30% and 17%, respectively.
      These results suggest that tacrine decreases the veratridine-induced
      catecholamine secretion primarily by inhibiting the voltage-dependent Na+
      channels rather than the Ca2+ channels. Physostigmine acts in a manner similar to
      tacrine, but its potency is much lower than that of tacrine.

PMID- 9646061
TI  - Passage of S-(+)- and R-(-)-ketoprofen across the human isolated perfused
      placenta.
AB  - Ketoprofen is a chiral non-steroidal anti-inflammatory drug (NSAID) available as
      a racemic (rac) mixture of S-(+)- and R-(-)-isomers. Its inhibitory effect on
      prostaglandin biosynthesis resides virtually in the S-form. Interestingly, R
      ketoprofen does not undergo substantial metabolic inversion in humans. Though
      contraindicated during the last trimester of pregnancy, NSAIDs, including
      ketoprofen, are used as tocolytic agents in some cases. The S/R plasma
      concentration ratio was reported to average 2.3 in premature neonates whose
      mothers were given rac-ketoprofen and to be close to 1 in the maternal plasma.
      Thus, we investigated the placental transfer of rac-ketoprofen in vitro using
      Schneider's perfused human cotyledon model. Glucosed Earle solutions with and
      without human serum albumin (HSA) were used. Several maternal perfusates were
      tested with different rac-ketoprofen concentrations together with 20 mg L-1 of
      antipyrine as a reference substance. Ketoprofen enantiomers were assayed by a
      specific HPLC method with derivatization procedure. HSA concentrations in
      maternal perfusate influenced the placental transfer of ketoprofen enantiomers.
      In the absence of HSA in the maternal perfusate, the S-(+)/R-(-) concentration
      ratio was close to 1 in the fetal perfusate. By contrast, this ratio averaged
      1.44 after addition of HSA 10 g L-1 on the maternal side. Similar results were
      found for dialysis experiments using an inert Spectrapor 2 membrane suggesting
      that the S-(+)-free concentration is superior to the R-(-)-free concentration in
      the presence of HSA. Direct measurements of the free concentrations by
      centrifugal ultrafiltration confirmed this hypothesis. Accordingly, the data
      observed in vivo may result, at least in part, from the stereoselective protein
      binding of ketoprofen.

PMID- 9646062
TI  - Effect of a single oral dose of two erythromycin ethylsuccinate formulations on
      gastric emptying in healthy volunteers: a scintigraphic study.
AB  - Macrolides are potential gastrokinetic agents. The purpose of this study was to
      assess the effect of a single oral dose of two erythromycin formulations on
      gastric emptying of the solid and liquid phases in twelve healthy volunteers and
      to seek a correlation between pharmacokinetic parameters and changes in gastric
      emptying. The gastric emptying times of liquids and solids were measured
      simultaneously by means of a scintigraphic technique after a single oral
      administration of amorphous erythromycin ethylsuccinate (500 mg), crystalline
      erythromycin ethylsuccinate (1000 mg) or a placebo, in a double-blind crossover
      study in three separate weeks. Blood samples were obtained for erythromycin
      assay. The two oral formulations induced a similar acceleration of gastric
      emptying. When compared to the placebo, both erythromycin preparations
      significantly shortened the gastric transit time of solids and liquids
      (respectively 30% and 20% on average, p < 0.01). The incidence of
      gastrointestinal side-effects was similar with the two erythromycin forms and the
      placebo. No correlation was found between the peak serum erythromycin
      concentrations and the solid or liquid gastric half-lives. With the amorphous
      formulation, the area under the plasma time-concentration curves was small and
      solid and liquid gastric emptying were strongly accelerated, pointing to a direct
      effect on the gastrointestinal smooth muscle.

PMID- 9646063
TI  - Organisation of a clinical trial unit--a proposal.
AB  - The urgent need for the performance of more, better designed, and better
      conducted randomised clinical trials is increasingly recognised. Based on
      structured interviews with leading persons of 43 outstanding organisations and
      units involved in clinical trials in Europe and North America during 1993, ways
      of organising and staffing clinical trial units were investigated. The present
      proposal is based on this experience from which an attempt to extract a composite
      set of minimal requirements has been made regarding pertinent objectives and
      aims, organisational aspects, staffing, and estimated costs of establishing a
      clinical trial unit. The core staff is suggested to consist of two chief
      physicians, one statistician, one data manager, one project coordinator, and two
      secretaries. In order to fulfil the minimal requirements for running such a unit,
      it is calculated that about GBP 450,000 per year is needed to cover investments,
      core staff, and running costs, but excluding housing costs and costs of
      randomised clinical trials that do not originate from trial coordination. In
      return, such a unit should be able to mount and launch 6-7 multicenter randomised
      clinical trials during a 5 year period, corresponding to a total cost for
      coordination per trial of about GBP 340,000. However, with a larger staff more
      studies may be coordinated possibly reducing the cost per trial depending on
      greater effectiveness in utilisation of the basic facilities.

PMID- 9646064
TI  - Clinical and epidemiological characteristics of juvenile myocardial infarction in
      Italy: the GISSI experience.
AB  - BACKGROUND: No clinical and epidemiological data are available about acute
      myocardial infarction (AMI) at a young age in large populations, due to the low
      prevalence of AMI in younger people. The aim of the present study is to analyze
      epidemiological and clinical characteristics of AMI among younger people in
      Italy, using the data bases of the three GISSI studies. METHODS: Analysis of
      epidemiological and clinical characteristics of AMI according to different age
      groups in the three GISSI studies that collected data from 1985 to 1993. RESULTS:
      In the GISSI-2 and GISSI-3 data bases, the prevalence of AMI at a young age (2
      and 1.8% respectively; difference -0.2% with 95% CI from -0.4 to 0.3%), hospital
      mortality (2.3 and 1.9% respectively; difference -0.4% with 95% CI from -1.9 to
      1.0%), and the rate of young female patients (8 and 7% respectively; difference 
      1% with 95% CI from -3.6 to 1.6%) are similar. In the GISSI-2 study, we observed
      that in comparison to elderly patients (> 70 years) young patients (< 40 years)
      are more frequently smokers (83.9 vs 21.0%; difference 62.9% with 95% CI from
      58.5 to 67.3%) and have a higher rate of family history for CAD (42.1 vs 21.1%;
      difference 21.0% with 95% CI from 15.3 to 26.7%) and of hypercholesterolemia
      (28.3 vs 15.0%; difference 13.3% with 95% CI from 18.5 to 80.8%), but show a
      lower prevalence of hypertension (12.2 vs 44.3%; difference from -32.1% with 95%
      CI from -28.0 to -36.2%) and diabetes (2.9 vs 18.8%; difference -15.9% with 95%
      CI from -13.5 to -18.3%). AMI at a young age is generally the first event in
      ischemic heart disease; in comparison with older patients with previous AMI (6.4
      vs 17.4%; difference -11.0% with 95% CI from -7.8 to -14.0%) and history of
      angina (23.2 vs 40.0%, difference -16.8% with 95% CI from -11.8 to -21.9%) this
      is less frequent. The rate of complications is lower in younger as opposed to
      older patients for both early (7.7 vs 31.2%; difference -23.5% with 95% CI from 
      20.0 to -26.9%) and late heart failure (2.9 vs 18.5%; difference -15.6% with 95%
      CI from -13.2 to -18.0%), as well as for angina (6.4 vs 10.5%; difference -4.1%
      with 95% CI from -1.1 to -7.1%), reinfarction (1.0 vs 3.3%; difference -2.3% with
      95% Ci from -1.1 to -3.6%) and complete AV block (1.6 vs 6.6%; difference -5.0%
      with 95% CI from -3.3 to -6.7%). In young patients, we observed lower in-hospital
      (1.6 vs 21.1%; difference -19.5% with 95% CI to -21.6%) and six-month mortality
      (1.3 vs 8.1%; difference -6.8% with 95% CI from -5.0 to -8.5%). CONCLUSIONS: The
      incidence and mortality of AMI at a young age was steady during the period
      between 1988 and 1993. AMI at a young age is a clinical entity with specific
      characteristics that differ from those found in old patients. In addition, it has
      peculiar risk profile with a better short- and medium-term outcome.

PMID- 9646065
TI  - [The Italian Journal of Cardiology, the English language and culture].

PMID- 9646066
TI  - Assessment of right ventricular function and interstitial fibrosis in idiopathic
      dilated cardiomyopathy: hemodynamic correlates and prognostic value.
AB  - BACKGROUND: Right ventricular (RV) function and morphometric quantitation of
      interstitial fibrosis in idiopathic dilated cardiomyopathy (IDC) have not been
      the subject of specifically designed clinical observations. In particular, their
      role in routine assessment and prognostic evaluation of patients (pts) with IDC
      remains to be settled. METHODS: Eighty-one consecutive IDC patients (63 M, 18 F;
      mean age 52 +/- 11 yrs) with left ventricular (LV) systolic dysfunction
      (angiographic ejection fraction - EF - < 55%), normal coronary arteries and no
      histologic evidence of myocarditis were studied. Cardiac catheterization and
      endomyocardial biopsy (EMB) were routinely performed in all cases. RV volumes and
      EF were obtained by angiography according to Ferlinz' method and interstitial
      fibrosis was quantitated by computer-assisted morphometric analysis. These data
      were analyzed in order to study correlations with hemodynamic parameters and to
      assess their prognostic value in a long-term follow-up. RESULTS: In the study
      population, right ventricular EF was significantly lower than in normal controls
      (35 +/- 11% vs 53 +/- 6%, p < 0.0001) and showed a significant positive
      correlation with LV EF (r = 0.54; p < 0.0001), and a weak but significant
      negative correlation with fibrosis (r = -0.29; p = 0.03). RV volumes, but not EF,
      were significantly related to mean pulmonary pressure. At multivariate analysis,
      RV end-diastolic volume (EDV) and EF were the two independent predictors of
      severe heart failure (NYHA class III-IV). After a mean follow-up of 64 +/- 36
      months, 20 pts died and 9 had heart transplantation, for a 63% transplant-free
      survival rate (TFS). Multivariate analysis identified three independent
      predictors of TFS: LV stroke work index (p < 0.0001), RV stroke work index (p =
      0.02) and RV EDV (p = 0.03). Fibrosis was predictive of survival only in the
      subgroup with LV EF < 20%. CONCLUSIONS: Assessment of RV function provides useful
      information in the evaluation of hemodynamic profile and prognosis of pts with
      IDC. Quantitation of interstitial fibrosis by morphometry provides little
      additional data.

PMID- 9646067
TI  - Doppler echocardiographic assessment of left ventricular isovolemic relaxation
      flow.
AB  - BACKGROUND: It is not infrequent to observe a peculiar intraventricular
      relaxation flow (IRF) pattern during the isovolumic relaxation time (IRT),
      especially in patients (pts) with left ventricular hypertrophy (LVH). This is
      even more likely in pts with hypertrophic obstructive cardiomyopathy and in VVI
      paced pts. Despite these observations, the prevalence and clinical relevance of
      this finding have not been evaluated thoroughly and systematically in a
      consecutive series of patients. METHODS: Ninety-two consecutive pts underwent a
      conventional Doppler echo study for the evaluation of systolic and diastolic
      function (fractional shortening, EF, E and A wave velocity, duration and ratio,
      and IRT). of these, 42 pts had LVH, 14 had mitral regurgitation (MR) with
      depressed EF, 8 had CAD with depressed EF and 28 were normal subjects. IF was
      searched for during the evaluation of IRT and its duration, velocity and integral
      were measured when noted. RESULTS: Fifty-six patients (61%) showed an IRF at
      Doppler examination. Of these, fifteen were normal subjects (53%) and 34 (81%, p
      = 0.03 vs normal) were hypertensive pts. Among pts with depressed EF, only two of
      14 with MR and 5 of 8 with no MR showed an IRF (14 vs 62%; p = 0.032). When
      evaluating LV function, we observed that pts with an IRF had a larger atrial
      filling fraction, a longer isovolumic relaxation time and a higher ejection
      fraction with respect to pts with no IRF (respectively, 40 +/- 13% vs 30 +/- 13%,
      p = 0.005; 108 +/- 23 ms vs 77 +/- 22 ms, p = 0.0001; 70 +/- 14% vs 61 +/- 16%, p
      = 0.01). CONCLUSIONS: Our data confirm that IRF may be observed in healthy
      subjects and may be due to an asynchronous relaxation of the LV during IRT, in
      consideration of a higher prevalence of a greater atrial filling fraction in pts
      with IF as compared to those in whom this Doppler signal is absent. Moreover, IRF
      is more frequent in pts with LVH and is rare in pts with MR (predominantly due to
      a very short isovolumic relaxation time).

PMID- 9646068
TI  - Relation between white blood cell count and several risk factors for coronary
      heart disease in patients with systemic hypertension.
AB  - BACKGROUND: Several epidemiological studies have shown a relation between white
      blood cell (WBC) count in peripheral blood samples and other cardiovascular risk
      factors. Such associations have also been described in patients affected by
      dyslipidemia. On the other hand, no data are available in patients with systemic
      hypertension. AIM: In a southern Italian population of hypertensive patients, in
      order to assess the relation between WBC count and other risk factors for
      coronary artery disease; in addition, to evaluate if a high WBC count can
      identify subgroups of hypertensives with a higher risk profile for
      atherosclerosis. POPULATION AND METHODS: We evaluated 147 consecutive patients
      (44 males, mean age 49 +/- 11 years) with a minimum 2-year history of systemic
      hypertension in the absence of ischemic heart disease and cerebrovascular
      disease. Among risk factors, we considered: hypercholesterolemia,
      hypertriglyceridemia, hyperglycemia and obesity. RESULTS: WBC count was
      significantly higher in patients with 2 or more risk factors (7.092 +/- 1034
      cells/dl than in hypertensives without risk factors (5.902 +/- 1167, p < 0.0001).
      WBC count was significantly associated with hyperglycemia (p < 0.001), number of
      cigarettes smoked daily (p < 0.004), fibrinogen plasma levels (p < 0.008) and
      azotemia (p < 0.009). Multivariate analysis has shown a positive significant and
      independent relation between WBC count and both hyperglycemia and number of
      cigarettes. CONCLUSIONS: These results emphasize that, among hypertensives,
      subgroups with a higher WBC count also have a higher risk profile for
      atherogenesis. The relation between WBC and some risk factors is confirmed by our
      data in a population of patients affected with systemic hypertension.

PMID- 9646069
TI  - [Role of stress myocardial perfusion scintigraphy in the follow-up of patients
      undergoing coronary angioplasty: comparison between qualitative and semi
      quantitative analysis].
AB  - In order to assess the diagnostic accuracy of stress/rest myocardial perfusion
      scintigraphy in the follow-up of patients undergoing percutaneous transluminal
      coronary angioplasty (PTCA) we studied 50 patients (pts) before and 6 months
      after PTCA. All patients underwent control coronary angiography and then were
      divided in 2 groups, according to angiographic evidence of restenosis (25 pts) or
      no restenosis (25 pts). Myocardial perfusion imaging was performed with 99mTc
      methoxy-isobutyl-isonitrile (MIBI). For MIBI scans, both qualitative and semi
      quantitative analysis were performed. SPECT images were displayed on a color
      monitor in random order and graded blindly by 2 experienced observers. Rest and
      stress MIBI uptake was scored using a 4-point scale (ranging from 0 = normal, to
      3 = absence of uptake). Individual subjects' perfusion scores were calculated by
      adding the individual segments' scores. History of relapsing angina showed a
      sensitivity and specificity of 76 and 96%, respectively. Exercise testing and
      MIBI tomoscintigraphy exhibited sensitivity and specificity of 80 and 56%, and 92
      and 44%, respectively. However, when considering semiquantitative data and
      comparing them with pre-PTCA studies, specificity of MIBI scan increased to 96%,
      while sensitivity decreased to 72%. The results of the present study confirm high
      sensitivity and low specificity for both exercise ECG and myocardial perfusion
      scintigraphy, in the detection of restenosis following PTCA. However, when
      performing semiquantitative analysis of perfusion scanning and comparison with
      pre-PTCA images, the specificity of MIBI tomoscintigraphy increases
      significantly. Therefore, when adopting myocardial perfusion scintigraphy for the
      follow-up of patients undergoing PTCA, a pre-revascularization scan should be
      obtained as often as possible. This approach, in the context of a positive test,
      makes feasible the assessment of often partial improvements in perfusion of the
      myocardium relative to the treated vessel, consequently avoiding many false
      positive results which invariably lead to coronary angiography.

PMID- 9646070
TI  - [Myocardial revascularization with both internal mammary arteries].
AB  - BACKGROUND: The excellent results obtained with the use of the left internal
      mammary artery (IMA) for myocardial revascularization have led to the
      simultaneous use of other arterial conduits, particularly the right IMA. METHODS:
      The present study includes the first 100 consecutive patients with ischemic heart
      disease who underwent myocardial revascularization with in situ bilateral IMA
      grafted to branches of the left coronary artery, performed at our center. Ninety
      six (96%) were males and four (4%) were females, with a mean age of 58 +/- 8
      years (range, 35-75 years). The main indication for myocardial revascularization
      was angina in 83 patients (83%) and heart failure in 17 (17%). Seventy patients
      had three-vessel disease. RESULTS: Hospital mortality was 1%, with one death due
      to left ventricular failure. Three patients had perioperative myocardial
      infarction, six experienced ventricular arrhythmia, two had acute renal failure
      and nine respiratory insufficiency. Dehiscence of the sternal wound occurred in
      four patients, evolving in mediastinitis in one. All discharged patients were
      checked after 26 +/- 6 months (range, 12-38 months). There were two deaths, one
      because of cardiac failure and one sudden death, with a two-year survival rate of
      97 +/- 2%. Five patients (5%) required hospitalization because of angina, and the
      angiographic study showed stenosis/occlusion of one or both IMAs in four cases.
      Thirty-five (38%) of the remaining patients underwent a coronarographic (25
      patients) or transthoracic Doppler study (10 patients) to evaluate patency of the
      IMAs. The patency index was 100% for the left IMA and 94% for the right IMA.
      CONCLUSIONS: Myocardial revascularization with bilateral IMA in situ can be
      performed with low hospital mortality and morbidity. Sternal dehiscence is the
      worst complication and appears to be more frequent in diabetic and elderly
      patients. Mid-term results are satisfactory, with a good survival rate and
      freedom from major cardiac events. However, a longer follow-up is necessary to
      better appreciate the advantages of myocardial revascualarization with in situ
      bilateral IMAs.

PMID- 9646071
TI  - [Rapid resolution of ST-segment elevation predicts functional recovery in acute
      myocardial infarction treated with primary percutaneous transluminal coronary
      angioplasty].
AB  - OBJECTIVES: This study was designed to prospectively assess the ability of the 12
      lead electrocardiogram (ECG) and optimal ECG criteria to predict late functional
      recovery in patients with acute myocardial infarction (AMI) treated with primary
      coronary angioplasty (PTCA) BACKGROUND: A simple clinical method to predict
      clinical outcome in patients with reperfused AMI is highly desirable from a
      clinical point of view. METHODS: Seventy-five patients with AMI treated with
      successful PTCA (TIMI flow grade 3 and residual stenosis < 30%) underwent serial
      12-lead ECG before PTCA and every hour for the first 6 hours and then at 9, 12,
      and 18 hours after PTCA. All patients underwent two-dimensional echocardiography
      before PTCA and 1 and 6 months later for the evaluation of regional wall motion.
      The ST segment level in the lead exhibiting the maximal ST elevation (ST increase
      max) and the sum of the ST segment elevation (sigma ST increases) were calculated
      on initial ECG and a cut-off values of > or = 50% reduction of ST increases max
      sigma ST increases elevation and sampling intervals were correlated with late
      functional recovery. A wall motion score index (WMSI: 1 = normal to 4 =
      dyskinesia) and 16-segment model were used. Reversible dysfunction was defined as
      a decrease of > or = 0.22 in WMSI. RESULTS: At univariate analysis a > or = 50%
      reduction of both ST increases max and sigma ST increases was related to late
      functional recovery. Multiple logistic regression analysis revealed that
      reduction of sigma ST increases was the most powerful predictor of late
      functional recovery (p = 0.008). A > or = 50% reduction of sigma ST increase
      within 4 hours of PTCA provided the optimal criterion for predicting late
      functional recovery. CONCLUSIONS: Rapid reduction of sigma ST increases elevation
      is an accurate predictor of left ventricular functional recovery in patients with
      AMI treated with primary PTCA. Optimal criteria include a reduction in sigma ST
      increases elevation > or = 50% within 4 hours of PTCA.

PMID- 9646072
TI  - A rare anatomic variation of the anomalous origin of all three major coronary
      arteries from the right sinus of Valsalva.
AB  - We describe the case of a patient with angiographic evidence in the right sinus
      of Valsalva of anomalous origin of LCx and common origin of LAD and RCA. This
      anomaly, which has not been reported previously, represents a further anatomic
      variation of the rare anomalous origins of all coronary arteries from right sinus
      of Valsalva. The symptoms in our patients were related exclusively to the
      atherosclerotic lesions in LCx and RCA and not to the anatomic anomalies. The
      patient underwent a bypass graft to LCx and RCA.

PMID- 9646073
TI  - [Massive pulmonary embolism after blunt chest trauma: considerations on
      pathogenesis and therapy].
AB  - A blunt chest trauma may provoke many different kinds of cardiac injury,
      particularly myocardial contusion, sometimes causing subsequent acute myocardial
      infarction or cardiac arrest by ventricular tachyarrhythmia in the absence of
      structural lesions. We describe a case of acute massive pulmonary embolism after
      a blunt chest impact caused when the patient was kicked by a horse. The patient
      showed progressive dyspnea three days after the trauma. The diagnosis was reached
      by non-invasive means and finally confirmed by pulmonary angiography. Because of
      the contraindication to thrombolytic therapy, we performed percutaneous catheter
      and guide-wire clot fragmentation with at least partial immediate success and
      subsequent favorable course. We discuss possible pathophysiological mechanisms to
      explain this case, which has no precedents in the literature.

PMID- 9646074
TI  - [Clocking diagnostic and therapeutic procedures in coronary care unit patients:
      analysis of clinical performance times].
AB  - BACKGROUND: An optimal use and exploitation of professional personnel is of
      paramount importance for health management organizations, as human resources are
      both their greatest asset and heaviest financial burden. To better understand the
      amount of medic and paramedic work and time required for the typical diagnostic
      and therapeutic procedures in a coronary-care unit setting, we measured their
      average times and analyzed their inherent co-factors. METHODS: This study was
      conducted on 206 consecutive coronary-care unit patients. These patients were
      divided into subgroups according to their admission diagnosis: acute myocardial
      infarction, unstable angina, acute cardiac failure, pulmonary embolism or other
      pathologies. Each subgroup was then subdivided even further according to the
      severity of their clinical status. Diagnostic and therapeutic procedures
      ("macroactivities") have been identified and each one was subdivided into sub
      procedures ("microactivities"). All microactivities were carefully clocked in
      every patient in order to calculate the average execution time for every
      macroactivity. RESULTS: Our data show that myocardial infarction patients and, in
      general, a more severe clinical status required a longer stay in the coronary
      care unit. Again, longer overall clinical performance times were necessary in
      myocardial infarction patients as compared to the unstable angina subgroup. There
      were no statistically significant differences among other subgroups. More
      severely ill patients required longer clinical performance times because of both
      a longer coronary-care unit stay and longer clinical performance time per day.
      More than half of the total clinical performance time for each patient was spent
      during the first two days. Paramedics supplied more than 80% of the total
      performance time. CONCLUSIONS: The authors undertook a study of typical coronary
      care unit clinical activities by clocking the performance times of the usual
      diagnostic and therapeutic procedures. The data thus obtained come from direct
      measurements and describe the clinical performance of both medics and paramedics
      in a real-life setting. This could thus be used as a yardstick to verify current
      workload standards. It is hoped that a deeper understanding of these activities
      will optimize the full exploitation of available human resources.

PMID- 9646075
TI  - [Role of cardiac first aid in a level-II Emergency Department].
AB  - We report our experience in the organization and management of a Cardiac First
      Aid Unit (CFAU) which was developed according to the guidelines of the National
      Hospital Cardiologists Association as a part of a General Emergency Department.
      The CFAU is a 24 hour service directed by a Senior Cardiologist. The medical
      facilities are two monitored beds for short-term observation (cardio-pulmonary
      resuscitation instruments, echocardiograph, endoesophageal pacing for overdrive).
      The main goals of CFAU are the treatment of cardiac emergencies (acute myocardial
      infarction, pulmonary oedema, threatening arrhythmias, etc.) and the screening of
      patients presenting with chest pain or symptoms suggesting cardio-vascular
      involvement. In one year, there were 1700 admissions to the CFAU (3.7% of the
      total Medical Emergencies). The frequency of hospital admissions was 81% and
      coronary heart disease accounted for 38.3%. A sample of 100 consecutive patients
      with acute myocardial infarction admitted in the period October-November 1996 was
      examined to explore the impact of a CFAU on in-hospital delay in the application
      of thrombolysis. Thirty-nine patients were treated with thrombolysis, 15 in CFAU
      and 24 in Coronary Care Unit (CCU). The mean in-hospital delay to thrombolysis
      was 30 +/- 14 minutes for those treated in CFAU and 55 +/- 12 minutes for those
      treated in CCU (p < 0.0004). In a second sample of 100 consecutive patients with
      undetermined chest pain, by means of our protocol of short observation we
      identified 22 cases of acute myocardial infarction (AMI), 8 cases of angina
      pectoris, 18 various cardiac causes, 30 non-cardiac causes, 22 absent disease.
      ECG was obtained in all 100 pts, cardiac enzymes in 74, echocardiogram and chest
      X-ray in 48, ST monitoring in 26. In no case was diagnosed AMI after discharge.
      Cardiac First Aid Unit, as designed in our Hospital, suits the needs of a level
      II Emergency Department. It is a useful tool to shorten in-hospital delay to
      thrombolysis and to screen chest pain with nearly complete safety.

PMID- 9646076
TI  - [From atherosclerotic plaque to coronary thrombus: pathophysiologic aspects of
      acute coronary syndromes].

PMID- 9646077
TI  - [Myocardial revascularization using the Vineberg procedure].

PMID- 9646078
TI  - [Clarification of "DRG and PRG in infarction"].

PMID- 9646079
TI  - [Sudden death in young people with mitral valve prolapse or mitral valve prolapse
      in young people who died suddenly].

PMID- 9646081
TI  - [Early discharge after myocardial infarction].

PMID- 9646082
TI  - Correlation of relative afferent pupillary defect and estimated retinal ganglion
      cell loss.
AB  - BACKGROUND: The relative afferent papillary defect (RAPD) is an important
      parameter for quantifying the loss of neuronal function in asymmetric optic nerve
      disease. We wanted to assess its correlation with retinal ganglion cell loss,
      estimated from visual field defects, using a recently described method. METHODS:
      In 36 patients with unilateral optic nerve disease, the RAPD was measured using
      an automated, computerized infrared pupillometer. The percentage of ganglion cell
      loss was estimated with clear templates. RESULTS: We found a highly significant
      correlation between the RAPD and estimated ganglion cell loss. The correlation
      was higher for Humphrey visual fields than for Goldmann visual fields measured
      with the 14e and 12e stimulus. CONCLUSION: The RAPD correlates well with
      estimated retinal ganglion cell loss in optic nerve disease. Humphrey visual
      fields seem to reflect the ganglion cell loss better than Goldmann visual fields.
      The spatial distribution of pupillomotor retinal ganglion cells seems to be
      proportional to the distribution of light-sensitive ganglion cells projecting to
      the lateral geniculate nucleus.

PMID- 9646083
TI  - Holmium:YAG thermokeratoplasty: treatment parameters for astigmatism induction
      based upon spherical enucleated human eyes.
AB  - BACKGROUND: The refractive outcome of thermokeratoplasty for astigmatism
      correction depends upon the optical zone diameter (OZD) and coagulation angle
      (CA; distance between two coagulation spots around the flat meridian). METHODS:
      Astigmatism was induced in 36 spherical human eye-bank eyes (Ho:YAG laser, 15 Hz,
      20 mJ/pulse, 25 pulses per coagulation spot) with different OZDs and CAs. Thirty
      eyes received free-hand laser application (marked positions). Six eyes were
      treated using a suction mask, providing a constant OZD of 8.1 mm and an angle of
      22.5 degrees between the laser spots. To compare the results, silicone replicas
      of the eyes were made pre- and postoperatively and analyzed by video-topometery.
      RESULTS: With an average decrease of 4 D/mm the refractive change is inversely
      linear to the OZD. Changes of the CA showed significant variations between 22.5
      degrees and 45 degrees, only. Mask guidance leads to the same amount of average
      refractive change. The deviation is +/- 3.4 D for the freehand application but
      only +/- 0.8 D for mask guidance. CONCLUSION: The data obtained in this in vitro
      study are transferred to a treatment nomogram describing the immediate
      postoperative refractive change, not identical with the final refraction. The
      results of the study are limited by the fact that astigmatism was induced in
      spherical corneas, rather than correcting preexisting ones.

PMID- 9646084
TI  - Retinal capillary density in patients with arterial hypertension: 2-year follow
      up.
AB  - BACKGROUND: Arterial hypertension is known to be an important risk factor for
      cerebral and cardiovascular disease. Previous studies have demonstrated a
      decrease of capillary density in the perifoveal network in tandem with decreased
      capillary flow velocity in patients with essential hypertension. In a prospective
      study we quantified the retinal microcirculation in order to evaluate the time
      course of changes in the perifoveal network. METHODS: Thirty-three patients with
      essential hypertension (mean age 45 +/- 14 years) underwent video-fluorescein
      angiographic studies at baseline and at 2 years 28 +/- 6 months) thereafter. The
      angiograms were obtained with a scanning laser ophthalmoscope and were digitally
      recorded. By means of digital image analysis we quantified off-line the mean area
      of perifoveal intercapillary areas (PIA) and the mean capillary flow velocity.
      RESULTS: At baseline, the patients with hypertension showed significantly
      increased PIA and a significantly decreased capillary flow velocity compared with
      reference values. During the follow-up period the capillary flow velocity
      decreased further significantly, whereas the PIA showed no significant change.
      CONCLUSIONS: The continuous decrease of capillary flow velocity demonstrates a
      progression of altered microcirculation in patients with essential hypertension
      whose blood pressure was believed to be well controlled. Further studies with
      this technique may be useful to determine the influence of antihypertensive
      therapy and may help to identify patients at risk for cerebrovascular events.

PMID- 9646085
TI  - Comparative immunohistochemical oestrogen receptor analysis in primary and
      metastatic uveal melanoma.
AB  - BACKGROUND: The investigation reported here was carried out to determine the
      oestrogen receptor status of metastatic and primary uveal melanomas. METHODS: A
      series of 23 primary and 24 metastatic formalin-fixed paraffin-embedded choroidal
      melanomas were analysed immunohistochemically with the monoclonal antibody (MAb)
      1D5 using the avidin-biotinylated peroxidase method and antigen retrieval with
      microwaves. Melanophages were identified with MAb PG-M1 to macrophages. RESULTS:
      None of the primary or metastatic melanomas contained tumour cells that would
      have shown a nuclear immunoreaction for oestrogen receptors with MAb 1D5.
      However, in 20 of the 23 primary tumours and in 14 of the 24 metastases a
      variable number of infiltrating cells showed a strong positive cytoplasmic
      immunoreaction with MAb 1D5. The cells contained pigmented cytoplasmic granules
      that resisted bleaching of melanin and their cytoplasm was strongly labelled with
      MAb PG-M1, identifying them as cross-reacting macrophages. CONCLUSION: Oestrogen
      receptors can not be used as a prognostic indicator if anti-oestrogen therapy is
      considered for treatment of metastatic uveal melanoma. However, because anti
      oestrogens also act by other mechanisms on both tumour and host tissues, the lack
      of oestrogen receptors does not automatically negate their therapeutic effect in
      disseminated melanoma.

PMID- 9646086
TI  - Conditions for balance between lower normal pressure control and hypotony in
      mitomycin trabeculectomy.
AB  - BACKGROUND: Striving for low to ultra-low postoperative intraocular pressure
      (IOP) through filtering surgery usually increases the incidence of prolonged
      hypotony. Early postoperative prognostic indicators for IOP control to lower
      normal level and prolonged hypotony in trabeculectomy with mitomycin C were
      examined to determine conditions required to obtain an optimum balance between
      them. METHODS: Records of initial trabeculectomy with mitomycin C (0.4 mg/ml, 3
      min) in 59 consecutively operated Japanese patients with primary open-angle
      glaucoma who had used multiple medications before operation were retrospectively
      analyzed. IOP control to lower normal level was defined as having failed if IOP
      could not be maintained below 15 mm Hg without medication. Prolonged hypotony was
      defined as postoperative IOP below 5 mm Hg for more than 2 months, excluding the
      first month. The Cox proportional hazards model was applied to identify early
      postoperative factors contributing to the two surgical outcomes. RESULTS: Among
      the factors studied, only the mean IOP on postoperative days 9-14 was
      significantly correlated with the surgical outcome. A receiver operating
      characteristic plot suggested that mean IOP of 8 mm Hg in this period would give
      an optimum balance between the two. CONCLUSION: IOP of 8 mm Hg 9-14 days after
      surgery may be advisable in patients with preoperative multiple medications in
      whom IOP control to lower normal level is attempted with mitomycin C
      trabeculectomy. Knowledge of this may be helpful in deciding when laser lysis of
      sutures is indicated.

PMID- 9646087
TI  - Aqueous flare in retinitis pigmentosa.
AB  - BACKGROUND: The purpose of this study was to quantify blood-ocular barrier
      impairment by measuring aqueous flare in retinitis pigmentosa (RP) and to search
      for clinical correlations. METHODS: Forty-nine patients (94 eyes) with RP and 85
      normal controls were examined. Aqueous flare was quantified with the noninvasive
      laser flare-cell meter (FC-1000, Kowa, Japan). Degrees of cystoid macular edema
      (CME), vitreous pigment dusting (VPD), intraretinal migration of retinal pigment
      epithelium, and waxy pallor of the optic nerve head were determined
      semiquantitatively by biomicroscopy. Data were analyzed using the t-test the Mann
      Whitney U-test, the chi-squared test and regression analysis by taking into
      account the dependency of data from two eyes of the same patients. RESULTS:
      Aqueous flare (photon counts/ms) was significantly higher in RP (mean 10.11 +/-
      3.53) than in normals (3.89 +/- 0.94; P < 0.001). Clinically significant CME was
      present in 26% of eyes with RP, being significantly more frequent in autosomal
      dominant RP (11 of 16 eyes, 69%) than in other variants (17%; P < 0.005).
      Multivariate analysis revealed that CME was most strongly associated with flare
      values (r = 0.84), P < 0.01), whereas--after adjusting for CME--correlations
      between aqueous flare and other clinical findings did not reach significance.
      CONCLUSION: RP eyes show increased aqueous flare values, indicating impairment of
      blood-occur barriers. This appears to be associated with CME and with autosomal
      dominant RP.

PMID- 9646088
TI  - Expression of Fas antigen on helper T lymphocytes in Vogt-Koyanagi-Harada
      disease.
AB  - BACKGROUND: Our purpose was to analyze the expression of Fas antigen on CD4+
      lymphocytes in the aqueous humor (AH) and cerebrospinal fluid (CSF) of patients
      with Vogt-Koyanagi-Harada disease (VKH). METHODS: Using three-color flow
      cytometry, we assessed T-lymphocyte subsets stained with fluorescence-conjugated
      anti-CD3, CD4, CD8, CD29, CD45RA, CD45RO, HLA-DR, and Fas monoclonal antibodies
      in AH, CSF and peripheral blood (PB) from 8 patients with active VKH. RESULTS:
      CD3+ T cells constituted the majority of lymphocytes in AH and CSF, in contrast
      to with PB. The percentages of CD4+ lymphocytes in uveitic AH and CSF were
      significantly higher than that in PB (P < 0.01). Activated CD4+ and CD8+ cells
      were significantly more frequent in AH than in CSF and PB (P < 0.01). Although
      the percentages of CD45RA+ cells within CD4+ cells in AH and CSF were extremely
      low compared with those in PB, the proportions of CD29+ and CD45RO+ (memory)
      cells within CD4+ were much higher than those in PB (P < 0.01). Fas antigen was
      also highly expressed on such CD4+ cells in AH, as in other uveitis patients and
      on such cells in CSF. Moreover, the percentages of Fas+ and memory cells in AH
      were significantly higher than those in CSF. CONCLUSIONS: The majority of CD4+
      lymphocytes in AH and CSF from patients with active VKH were activated memory
      cells, on which Fas antigen was also highly expressed. Although this Fas
      expression may not be an apoptosis-related phenomenon, accumulation of Fas+
      memory T lymphocytes in AH and CSF probably reflects the immunopathologic
      mechanism of VKH.

PMID- 9646089
TI  - The development of visual pursuit during the first months of life.
AB  - BACKGROUND: There are few previous investigations of smooth pursuit in infants.
      The aim of our study was to quantify visual pursuit in infants between 1 day and
      16 weeks of age. METHODS: Eye movements of 97 healthy infants between 1 day and
      16 weeks of age were recorded one to seven times with infrared photo-oculography.
      For stimulation of visual pursuit a square of 9.4 deg of visual angle with
      vertical gratings moved horizontally at a constant velocity of 7.5 deg/s.
      RESULTS: In the first 2 weeks of life, segments of smooth pursuit were measured
      with a maximum velocity of 7.93 deg/s, with a maximum gain of 1.06 and a maximal
      duration of 3.16 s. In sequential recordings no significant increases of
      velocity, gain or duration were found. However, the total time the subjects
      followed the stimulus with smooth plus saccadic pursuit increased significantly
      with age (from a median of 39.0% to a median of 61.5% of examination time).
      CONCLUSION: This study clearly demonstrates that smooth pursuit is already
      present in the first week of life. We found no significant increase in velocity,
      gain and duration of smooth pursuit segments in the first 16 weeks of life with
      our recording technique. However, the total pursuit time, reflecting attention,
      increased with age. The ocular machinery to drive pursuit appears to be in place
      at birth and seems not to be influenced by increased attention in the first
      months of life.

PMID- 9646090
TI  - Radiating retinal folds detected by scanning laser ophthalmoscopy using a diode
      laser in a dark-field mode in idiopathic macular holes.
AB  - BACKGROUND: The pathogenesis of idiopathic macular hole is unclear. We studied
      the morphologic features of idiopathic macular holes using a modification of the
      scanning laser ophthalmoscope (SLO). METHODS: Seventy-two eyes of 57 patients
      with macular hole (40 women, 17 men; age 66.1 +/- 6.4 years, mean +/- SD) were
      included in this study. The macular holes were classified according to the Gass
      classification (1988). The changes around the macular holes were recorded by SLO
      using both a confocal aperture with a helium-neon laser (633 nm) and a ring
      aperture (dark-field mode) with a diode laser (780 nm) to detect fine morphologic
      features. RESULTS: We successfully observed minute retinal wrinkling, i.e.,
      radiating striae (fold type) and a dome configuration (dome type), around the
      macular holes using the SLO dark-field mode with a diode laser, which provides a
      deeper retinal image because of the longer wave-length laser and the indirect
      mode. A helium-neon laser with a confocal aperture sometimes failed to disclose
      the fine retinal wrinkles. Most of the stage 2 macular holes were of the fold
      type. The smaller the hole, the higher the prevalence of the fold type. As the
      holes progressed in size, the prevalence of the dome type increased. The
      radiating retinal folds disappeared after successful vitreous surgery.
      CONCLUSION: The SLO dark-field mode with a diode laser might be useful for clear
      observation of fine retinal features around macular holes. The retinal folds
      probably indicate the presence of traction on the macula and hence may be good
      markers for macular repair after vitreous surgery.

PMID- 9646091
TI  - Peripheral multifocal chorioretinitis with panuveitis: clinical and immunogenetic
      characterization in older patients.
AB  - BACKGROUND: The etiology of peripheral multifocal chorioretinitis with panuveitis
      (MCP) is unclear. Characteristic signs of MCP are punched-out, white
      chorioretinal lesions of the lower fundus periphery, chronic smoldering
      chorioretinal inflammation, vitritis, and mild inflammation of the anterior
      chamber. In this retrospective study we investigated clinical and immunogenetic
      abnormalities in MCP in older patients. PATIENTS AND METHODS: 20 patients (18
      women, 2 men), median age 70.5 years, were investigated clinically by
      ophthalmologists and were typed for HLA class I antigens using the standard
      microlymphocytotoxicity test. Typing for HLA-DR antigens was performed by
      polymerase chain reaction with sequence-specific primers (PCR-SSP). The HLA
      controls consisted of healthy people (108 for HLA class I, 114 for HLA class II).
      RESULTS: MCP was bilateral in 18 patients. Disease-related symptoms were present
      for 8 months (median) before diagnosis. The main presenting symptoms or findings
      were glaucoma (in 11 patients), visual loss (7), iritis (5), and vitritis (2).
      Anterior segment changes were frequently seen: keratitic precipitates (32 eyes),
      anterior chamber cells (25 eyes), aqueous flare (26 eyes), posterior synechiae
      (22 eyes), secondary glaucoma (15 eyes), and iris neovascularization (8 eyes).
      All patients had vitritis and typical chorioretinal fundus lesions. Fourteen
      patients developed cystoid macular edema (bilateral in seven cases). Subretinal
      neovascularization occurred in three patients. Although systemic medication was
      given to 17 patients and surgical treatment was performed in 25 eyes, improvement
      in vision was found in only 6 eyes, but 18 eyes deteriorated markedly (median 5
      lines) during follow-up (median 24.5 months). Immunogenetically significant
      reduced frequencies of HLA-B7 and HLA-DR1 were found; also HLD-DR15(2) was
      reduced. However, several alleles were increased in MCP, although not
      significantly: HLA-A31; HLA-B57, HLA-B62; HLA-Cw3, HLA-Cw6; HLA-DR4, HLA-DR7, and
      HLA-DR8. CONCLUSIONS: MCP is clinically and immunogenetically open to
      speculation. The present diagnosis and treatment of MCP are insufficient. Further
      DNA typing methods should clarify, whether HLA-DQ antigens are associated with
      the disease.

PMID- 9646092
TI  - Thalidomide inhibits corneal angiogenesis induced by vascular endothelial growth
      factor.
AB  - BACKGROUND: Ocular diseases caused by neovascularization are among the leading
      causes of blindness. No specific pharmacological treatment is available. Among
      potential drugs, thalidomide deserves special interest since a wide body of
      clinical experience exists. However, its antiangiogenic effect is controversial.
      We therefore investigated the effect of thalidomide on corneal angiogenesis
      induced by vascular endothelial growth factor (VEGF), which has a special role
      among angiogenic growth factors. METHODS: Corneal neovascularization was induced
      in NZW rabbits by an intrastromal pellet loaded with 500 or 750 ng VEGF. Animals
      received two daily feedings of 200 mg/kg thalidomide. RESULTS: Significant
      inhibition of corneal angiogenesis (P < 0.0001) was caused by the teratogenic
      dose of thalidomide after the 5th day of treatment and persisted for more than 16
      days. No obvious side effects were recorded. CONCLUSIONS: Thalidomide has a
      significant antiangiogenic effect against VEGF-induced neovasclar growth.
      Together with earlier findings this observation indicates that the drug inhibits
      two angiogenic pathways which are mediated through integrin adhesion molecules.

PMID- 9646093
TI  - A mouse model to study the wound healing response following filtration surgery.
AB  - BACKGROUND: Failure of trabeculectomy is attributed to an exaggerated wound
      healing response at the episcleral level. We have developed a simple technique in
      mice that creates corneoscleral wounds and used it to study the role of growth
      factors in wound healing associated with loss of fistular patency. In addition,
      the effect of suramin on the wound healing response has been investigated.
      MATERIALS AND METHODS: Using black C57B1/6 mice, we created a fistula from the
      subconjunctival space to the anterior chamber by external penetration with a 25
      gauge needle through the bulbur conjunctiva. Eyes were examined by light
      microscopy at different times following surgery and evaluated for the presence of
      growth factors in the sclerosing wound by immunohistochemistry. In an additional
      group, suramin (1.0 mg/ml) was applied topically five times. RESULTS: The
      limbal/scleral wounds closed rapidly. Granulation tissue consisting mostly of
      fibroblasts developed within the first 2 days, and the collagen component
      increased over time. By 4 weeks, the wound was completely healed. We found that
      within 1 day after surgery GF beta 2 reached high intensity. TGF beta 1 and PDGF
      A reached maximal intensity by day 2 and remained elevated for about a week, PDGF
      B was present at moderate intensity even before surgery. Myofibroblastic
      differentiation was observed from days 2 to 7. Suramin-treated wounds showed a
      decrease of cells and delay in fibroblast maturation. TGF beta 1 and TGF beta 2
      levels persisted longer than in the controls, while PDGF A and PDGF B levels were
      lower than in the controls at all time points. CONCLUSIONS: The mouse
      corneoscleral wound model that we have developed mimics the process of wound
      healing and fistulizing surgery that takes place in other animal models and in
      human eyes in which the outcome of the surgery is poor. Our analysis of the
      appearance of growth factors associated with wound healing demonstrates that PDGF
      A as well as TGF beta 1 and TGF beta 2 appear early in the process at high levels
      and are potential targets for interventive strategies to ensure channel patency.
      Suramin has a distinct effect on the wound healing process and expression of
      growth factors and may be a promising substance for clinical use.

PMID- 9646094
TI  - Toxoplasmic retinochoroiditis: resolution without treatment of the perilesional
      satellite dark dots seen by indocyanine green angiography.
AB  - PURPOSE: Satellite dark dots (SDD) seen by indocyanine green angiography (ICGA)
      around the main retinochoroiditis focus are described in 75% of cases. Whether
      SDDs represent subclinical infectious foci or just a perilesional inflammatory
      reaction is not known. The purpose here was to report a case giving additional
      information on this question. METHODS: We analysed the evolution of ICGA SDDs in
      a patient with recurrent toxoplasmic retinochoroiditis who received no
      antitoxoplasmic treatment because the lesion was located outside the areas where
      treatment is classically recommended. RESULTS: The patient had a recurrence of
      retinochoroiditis on the nasal aspect of the disc about 2 disc diameters away
      from the disc. It was decided to observe the recurrence before introducing
      treatment. Diminution of SDDs occurred by 3 weeks after the initial ICGA, and
      complete resolution was observed on a follow-up ICG angiogram obtained 8 weeks
      after the initial visit. CONCLUSION: Resolution of ICGA SDDs in toxoplasmic
      retinochoroiditis seems to occurring a similar fashion whether or not the
      retinochoroiditis is treated by anti-toxoplasmic drugs, indicating that SDDs
      probably represent a non-infectious perilesional inflammatory reaction.

PMID- 9646095
TI  - [Coronary heart disease as inflammatory disease of the vascular bed? Etiology,
      sequela or misconception?].
AB  - In this editorial the traditional risk factors are contrasted with more recent
      modifications of the response to injury theory including the modified LDL
      response to injury and the immunological response to injury theories. This issue
      of "Herz" is devoted to the missing points in the classic risk factor concepts
      and revisits them as well as the infectious theory with Chlamydia pneumoniae,
      cytomegalovirus and helicobacter pylori as well as the autoreactivity hypothesis.

PMID- 9646096
TI  - [Arteriosclerosis and coronary heart disease--strengths and weaknesses in the
      classical risk factor concept].
AB  - Several cardiovascular risk factors were identified (high LDL-cholesterol, low
      HDL-cholesterol, homocystein, Lp(a), and many others). Hypercholesterolemia has
      been shown to be one of the most important cardiovascular risk factors in man.
      Interventional studies for primary and secondary prevention demonstrate a
      beneficial effect of cholesterol lowering therapy. However, numerous CAD-patients
      suffer a second coronary event despite the appropriate lipid-lowering treatment.
      Furthermore moderate hypercholesterolemia has only poor predictive power
      indicating an upcoming myocardial infarction. Therefore we need additional
      research in CAD prevention and in identifying so far unknown or unconsidered CAD
      risk factors.

PMID- 9646097
TI  - [An alternative hypothesis of the pathogenesis of atherosclerosis].
AB  - Why LDL entrapped in the subendothelium should trigger events leading to chronic
      inflammation and to arterial wall injury is a major enigma of modern medicine.
      Oxidation of LDL in vitro renders the molecule potentially atherogenic, and the
      concept that oxidation is the major single event underlying the transformation of
      LDL to a proinflammatory molecule dominates the world literature. Here, an
      alternative hypothesis on the pathogenesis of atherosclerosis will be presented.
      We have found that non-oxidative, enzymatic modification of LDL with ubiquitous
      enzymes (protease + cholesterol esterase + neuraminidase) also transforms the
      molecule to an atherogenic moiety. Enzymatically altered LDL (E-LDL) shares major
      properties in common with lipoproteins that have been isolated from
      atherosclerotic lesions. It activates complement via the alternative pathway and
      is recognized by a scavenger receptor on human macrophages, thus inducing foam
      cell formation. Uptake of E-LDL is accompanied by potent induction of MCP-1
      synthesis and secretion. In contrast, E-LDL does not stimulate IL-1 or TNF
      production and is only a weak inducer of IL-6. Monoclonal antibodies were
      produced that recognize neoepitopes on E-LDL, but that do not react with native
      or oxidized LDL. With the use of these antibodies, extensive deposition of E-LDL
      in very early atherosclerotic lesions was demonstrated. Activated complement
      components colocalized with E-LDL, corroborating the concept that
      subendothelially deposited LDL is enzymatically transformed to a complement
      activator at the earliest stages in lesion development. The pathogenetic
      relevance of unhalted complement activation in atherogenesis was demonstrated
      with the use of C6-deficient rabbits. It was found that C6-deficiency markedly
      protected against development of diet-induced atherosclerosis in the experimental
      animals. In sum, our hypothesis departs from the mainstream of atherosclerosis
      research and derives from the recognition that extracellular exposition of free
      cholesterol in LDL-particles by itself confers pro-inflammatory properties onto
      the lipoprotein molecule. We believe that the degrading enzymes are ubiquitously
      present in the extracellular matrix, so the only requirement for atherogenesis to
      occur is the deposition of large amounts of LDL. Oxidative processes or
      infections probably play only minor roles, and reduction of LDL plasma levels
      will predictably represent the single most important prophylactic measure against
      development and progression of atherosclerosis.

PMID- 9646098
TI  - T-lymphocytes and monocytes in atherogenesis.
AB  - Atherosclerosis is characterized as a chronic inflammatory-fibroproliferative
      disease of the vessel wall. The attachment of monocytes and T-lymphocytes to the
      injured endothelium followed by their migration into the intima is one of the
      first and most crucial steps in lesion development. The co-localization of CD4+ T
      cells and macrophages in the lesion, the abundant expression of HLA Class II
      molecules and the co-stimulatory molecule CD40 and its ligand (CD40L) indicate a
      contribution of cell-mediated immunity to atherogenesis. Transgenic mouse models
      revealed that dependent on the model T- and B-cells may promote lesion
      progression, monocytes and macrophages are in contrast essential for the
      development of atherosclerotic lesions. Apart from the local process in the
      vessel wall, systemic signs of an inflammatory reaction are also associated with
      lesion development. Thus plasma levels of C-reactive protein and fibrinogen and
      the white blood cell count are positively correlated to the risk of
      cardiovascular disease. Recently, an inflammatory phenotype of circulating
      peripheral blood monocytes could be demonstrated as a specific cellular correlate
      to lipid and lipoprotein risk factors. Thus the pool size of LPS receptor
      (CD14)dim and Fc gamma IIIa receptor (CD16a)+ monocytes positively correlates to
      plasma cholesterol levels, to triglycerides levels and to the apolipoprotein E4
      (apo E4) phenotype in contrast to a negative correlation to the high density
      lipoprotein (HDL) cholesterol concentration. This CD14dim CD16a+ monocytes are
      further characterized by a high expression of beta 1- and beta 2-integrins,
      suggesting a higher capacity for attachment at sites of inflammation. A
      proinflammatory cytokine pattern and an expansion of these cells in other
      inflammatory diseases are indicating that these cells promote the inflammatory
      process during atherogenesis. Surface expression of the activation antigen CD45RA
      on monocytes in correlation to plasma LDL cholesterol and Lp(a) levels further
      indicates an inflammatory reaction. Regarding the potential mechanisms of the
      phenotypic changes of peripheral blood monocytes, in a serum free in vitro
      differentiation model supplemented with M-CSF monocytes from probands which are
      homozygous for apo E4 showed a significantly higher increase of CD16a expression
      compared to apo E3/E3 cells indicating that a genetic polymorphism of a single
      apolipoprotein gene locus may affect monocyte differentiation. The further
      characterization of the cellular immunology of monocytes and T-lymphocytes in
      lesion development will provide new specific diagnostic and therapeutic targets
      in atherogenesis.

PMID- 9646099
TI  - [Persistence of Chlamydia pneumoniae in human arteriosclerotic plaque substance.
      Evidence and consequences].
AB  - The obligate intracellular bacterium Chlamydia pneumoniae has recently been
      implicated in the pathogenesis of atherosclerosis. Serological response to
      Chlamydia pneumoniae statistically indicates an increased risk of coronary artery
      disease and myocardial infarction. This surprising relation is corroborated by
      the presence of chlamydial structures and even viable Chlamydia pneumoniae in
      atherosclerotic plaques. These findings have already resulted in initial studies
      on the potential benefit of antimicrobial therapy in coronary heart disease.
      However, experimental proof of an etiological role of Chlamydia pneumoniae in
      arteriosclerosis has not yet been accomplished since a well established animal
      model and a system of genetic recombination are not yet available. In addition,
      clinical evaluation of patients is complicated by the lack of a useful parameter
      to indicate the risk of endovascular infection. Whether chlamydiae initiate
      atherosclerotic injury. facilitate progression of existing plaques, or merely
      colonize the lesions is therefore not known. Chlamydial contribution to the
      development of atherosclerosis is a fascinating hypothesis that may initiate a
      radical change of clinical practice for one of the leading causes of death. At
      the current state of scientific knowledge, however, an experimental
      antichlamydial treatment in coronary heart disease may only be justified in well
      controlled clinical trials.

PMID- 9646100
TI  - [Arteriosclerosis as a sequela of chronic Chlamydia pneumoniae infection].
AB  - In the last years several new data allow a controversial but convincing
      interpretation of the pathogenesis of atherosclerosis (arteriosclerosis).
      Atherosclerosis can be apparently the result of ultrachronic persistent infection
      by Chlamydia pneumoniae and not the result of different risk factors. The main
      arguments for the chlamydial genesis are: 1. Correlation of coronary heart
      disease and other atherosclerotic disease with antibodies against C. pneumoniae.
      2. C. pneumoniae could be detected with different techniques (PCR,
      immunohistology, electromicroscopy, culture) in a high percentage in atheromas
      from different sites. 3. Three international studies with macrolides in coronary
      heart disease were successful. 4. The target cells of atherosclerosis
      (endothelia, macrophages, muscle cells) can be infected by C. pneumoniae in
      vitro. 5. Positive animal experiments. The Koch-Henle criteria for the proof of
      the etiology are largely fulfilled--even if there are doubts about the validity
      of these criteria in chronic local infections. A number of unexplainable aspect
      of atherosclerosis can be seen in a new light. The higher incidence of coronary
      heart disease in young males has a parallel in the remarkable androtropism of
      many bacterial diseases (pneumococcal pneumonia, tuberculosis). The reduction of
      incidence of atherosclerotic diseases since 1965 can be explained by the much
      higher intake of doxycyclin and macrolides. The low incidence of coronary heart
      disease in France--sometimes regarded as an effect of red wine--can be explained
      as a result of a much higher use of antichlamydial antibiotics. The increase of
      inflammatory parameters (C-reactive protein, fibrinogen, leucocytes) before acute
      coronary infarction are not risk factors but signs of an active chronic
      infection. The interpretation is possible, that atherogenic changes in lipids
      like increase of LDL and decrease of HDL are not risk factors but consequence of
      chronic arterial infection by chlamydia. The low incidence of atherosclerosis in
      the tropics--despite high frequency of chlamydial infection--is difficult to
      explain. Vascular infection can be related with the age of the patient at the
      primary infection. With low hygiene, intestinal primary infections in early
      childhood can be possible. Arterial infection would be thus a result of a primary
      infection in adolescence ("yet another poliomyelitis story"). There are good
      arguments for the thesis that C. pneumoniae is the primary cause of
      atherosclerosis and not a secondary invader. The consequence, nevertheless, is
      similar: Antibiotics get a key role. The macrolides roxithromycin, azithromycin,
      clarithromycin and the tetracyclin doxycyclin fulfill the criteria as potential
      antichlamydial agents. In general a longer treatment (6 to 8 to 12 weeks) seems
      advisable. It is necessary to start international studies with antibiotics in
      coronary infarction and other clinical manifestations of atherosclerosis. The
      relevant antibiotics licensed for chlamydial infections are cheap and safe.
      Despite of the urgent need for controlled studies, it seems already justified to
      treat high-risk patients with antibiotics. Meticulous protocols and long-term
      control of patients are necessary to evaluate the therapeutic effects. Preventive
      studies in patients without clinical manifestation of atherosclerosis are
      urgently needed. The risks of resistance or side effects are neglectable, but the
      organisation of such studies would be very difficult.

PMID- 9646101
TI  - [Cytomegalovirus and herpes simplex virus in pathogenesis and progression of
      native arteriosclerosis and recurrent stenosis after intervention].
AB  - An increasing number of clinical and experimental studies point to a contribution
      of various infectious organisms like chlamydia pneumoniae or herpesviruses to
      atherosclerosis in man. Cytomegalovirus induces atherosclerotic lesions in
      animals. In vitro studies reveal functional changes of endothelial cells after
      infection with cytomegalovirus. Infection with this virus renders endothelial
      cells immunogenic for cellular and humoral immune reactions. In man a significant
      association of infections with herpesviruses and atherosclerosis could be
      established in several studies. Cytomegalovirus infection has been incriminated
      as an independent risk factor in restenosis after coronary angioplasty.

PMID- 9646102
TI  - Transplant vasculopathy.
AB  - Transplant vasculopathy constitutes the major impediment to long-term survival in
      heart transplant recipients. Within the "response to immune injury" paradigm, it
      can best be understood as the resultant of an orchestrated recipient immune
      response to the initial allogenic stimulus by graft vascular endothelium. This
      response incorporates the elaboration of complex coordinated cytokine patterns
      and corresponding cell types including B-lymphocytes, T-helper1- and T-helper2
      cells, cytotoxic T-cells, macrophages, and polymorphonuclear cells. These attack
      the alloantigenic vascular endothelium and lead, by complex cytokine signaling,
      to migration of donor smooth muscle cells from the media into the intima,
      associated with a switch from the contractile to a synthetic phenotype. In
      conjunction with recipient T-cells, macrophages, and lipids, the intimal
      fibroproliferative growth of the donor vessel is hereby initiated.

PMID- 9646103
TI  - Acute parvovirus B19 infection in pregnant women--an analysis of serial samples
      by serological and semi-quantitative PCR techniques.
AB  - The serological and virological course of parvovirus B19 infection was followed
      in 14 women who suffered symptomatic or subclinical acute infection during
      pregnancy. Serial serum samples from the patients were tested for IgG and IgM
      antibodies and the levels of parvovirus B19 DNA were monitored using a semi
      quantitative PCR assay. In addition, the outcome of the pregnancies was
      documented by clinical information and by testing cord blood for parvovirus B19
      specific antibodies as well as for parvovirus B19 DNA by PCR. Levels of IgG
      antibodies rose steadily within 2 months of infection and in some cases began to
      decline at the end of pregnancy. IgM antibodies were usually detected for at
      least 2 months and persisted for as long as 9 months in one case. Viral DNA was
      detectable for at least 8 weeks following infection and semi-quantitative
      analysis revealed a gradual reduction in virus load during the viraemic phase of
      infection. There were no apparent differences in the course of antibody
      development and duration of viraemia in symptomatic versus subclinical
      infections.

PMID- 9646104
TI  - In vitro conversion of Borrelia burgdorferi to cystic forms in spinal fluid, and
      transformation to mobile spirochetes by incubation in BSK-H medium.
AB  - The purpose of this study was to examine the structural alterations of Borrelia
      burgdorferi when exposed to spinal fluid. Normal, mobile spirochetes were
      inoculated into spinal fluid, and the spirochetes were converted to cysts
      (spheroplast L-forms) after 1-24 h. When these cystic forms were transferred to a
      rich BSK-H medium, the cysts were converted back to normal, mobile spirochetes
      after incubation for 9 to 17 days. The cultures were examined by dark field
      microscopy (DFM), interference contrast microscopy (ICM) and transmission
      electron microscopy (TEM). When neuroborreliosis is suspected, it is necessary to
      realize that B. burgdorferi can be present in a cystic form, and these cysts have
      to be recognized by microscopy. This study may also explain why cultivation of
      spinal fluid often is negative with respect to B. burgdorferi.

PMID- 9646105
TI  - Antibody testing and RT-PCR results in hepatitis C virus (HCV) infection: HCV-RNA
      detection in PBMC of plasma viremia-negative HCV-seropositive persons.
AB  - To evaluate the concordance between viremia and antibody testing in hepatitis C
      virus (HCV) diagnosis, 682 serum or plasma samples collected from patients with
      known or suspected HCV infection were tested. An overall concordance of 77%
      between serological and PCR results was found, 5% was RNA positive/antibody
      negative and 18% antibody positive/RNA negative. The relationship between HCV
      infection, risk group and clinical diagnosis was studied in 116 patients: the
      presence of anti-HCV antibody without viremia was shown in 72.7% of asymptomatic
      subjects and 17.6% of chronic hepatitis subjects without interferon treatment.
      However, the detection of HCV-RNA in peripheral blood mononuclear cells (PBMC) in
      four out of 38 plasma viremia-negative HCV-seropositive subjects (10.5%), showed
      that HCV-RNA could persist in PBMC and could begin the viral replication again at
      different times. The detection of HCV-RNA in PBMC in anti-HCV-positive subjects
      without viremia could reduce false-negative results of HCV-RNA testing by RT-PCR
      in serum or plasma.

PMID- 9646106
TI  - Gram-negative bacteremia in non-neutropenic patients: a 3-year review.
AB  - The causative organisms, clinical manifestations, factors influencing prognosis,
      and other epidemiological characteristics of 81 episodes of bacteremia due to
      gram-negative organisms, in non-neutropenic patients, were studied
      retrospectively during a 3-year period (1992-1994) at the Department of Internal
      Medicine of the University Hospital of Heraklion, Crete, Greece. The gram
      negative bacteremia incidence was 2% and the overall mortality 12%. All 81
      patients had fever; Escherichia coli was the most frequent organism isolated
      (from 47 patients--58%) and was associated with shock (9/47), disseminated
      intravascular coagulation (DIC) (8/47), anuria (5/47), adult respiratory distress
      syndrome (ARDS) (3/47), and pneumonia (1/47). Other less frequent gram-negative
      microorganisms were Klebsiella spp. (ten patients; 12%), Pseudomonas spp. (7;
      7%), Salmonella spp. (5; 6%), Enterobacter spp. (5; 6%), Proteus spp. (3; 3.4%),
      Stenotrophomonas spp. (3; 3.4%), and Acinetobacter spp. (1; 1.2%). ARDS. shock,
      DIC, anuria, presence of central venous catheter, urinary catheter, unknown
      origin of infection and inappropriate treatment were significantly associated
      with a higher death rate. Early initiation of appropriate therapy was the most
      important intervention that favorably affected the outcome of gram-negative
      bacteremias in this patient population.

PMID- 9646108
TI  - Intracellular activity of vancomycin and Ly333328, a new semisynthetic
      glycopeptide, against methicillin-resistant Staphylococcus aureus.
AB  - The activity of vancomycin and Ly333328, a new semisynthetic glycopeptide,
      against eight strains of Staphylococcus aureus showing various susceptibilities
      to methicillin and ciprofloxacin was examined using a colony count method. We
      compared the growth of strains ingested by polymorphonuclear leucocytes and non
      ingested strains. MICs of vancomycin and Ly333328 against staphylococci resistant
      and susceptible to methicillin were 2 mg/l and 2-4 mg/l, respectively. Against
      all the tested extracellular staphylococci, vancomycin had only bacteriostatic
      activity, whereas Ly333328 showed cidal activity at 10 MIC. Against ingested
      staphylococci, vancomycin had nearly no activity compared with the controls,
      regardless of the concentration of the drug. Ly333328 at concentrations of 1 MIC
      and above was highly active against ingested staphylococci regardless of their
      susceptibility pattern. The results suggest that Ly333328 in contrast to
      vancomycin is active against intracellular S. aureus.

PMID- 9646107
TI  - Concomitant infection with tick-borne encephalitis virus and Borrelia burgdorferi
      sensu lato in patients with acute meningitis or meningoencephalitis.
AB  - From September 1992 to August 1993, 338 patients over the age of 15 years
      presented to the Department of Infectious Diseases, University Medical Centre
      Ljubljana, with acute lymphocytic meningitis. In 89 of these patients (26.3%)
      serum IgM and IgG antibodies against tick-borne encephalitis (TBE) virus were
      detected, and in 59 patients (17.5%) a borrelial etiology of disease was
      demonstrated by one or more of the following presence of intrathecal antibody
      production, seroconversion to borrelial antigens, presence of erythema migrans,
      and/or isolation of Borrelia burgdorferi sensu lato from skin or cerebrospinal
      fluid. Of the 148 patients who fulfilled criteria for TBE or borrelial infection,
      concomitant infection with TBE virus and B. burgdorferi sensu lato was
      demonstrated in 12 patients (3.6% of all patients presenting with acute
      lymphocytic meningitis). In the majority of patients with concomitant infection
      the clinical features at presentation were characteristic of, or consistent with,
      TBE. In addition, during follow-up studies, eight of the 12 patients subsequently
      developed signs and symptoms compatible with minor and/or major manifestations of
      Lyme borreliosis. Six patients were diagnoses with neuroborreliosis based on
      signs or symptoms and/or laboratory tests. These findings show that in patients
      with acute lymphocytic meningitis or meningoencephalitis, originating in TBE and
      Lyme borreliosis endemic regions, the possibility of concomitant infection should
      be considered.

PMID- 9646109
TI  - Serum procalcitonin rise is only slight in two cases of disseminated
      aspergillosis.
AB  - High serum concentrations of procalcitonin (PCT) have been found during bacterial
      and parasitic infections. This is a report of two cases of disseminated
      aspergillosis with moderate PCT increase in two 14-year-old girls after bone
      marrow transplantation (BMT) for myelodysplastic syndrome and Fanconi's anemia,
      respectively. In contrast, the important rise of serum CRP observed in these
      patients tends to demonstrate that the synthesis of these two proteins is under
      different control mechanisms.

PMID- 9646110
TI  - Investigation of Rickettsia conorii antibodies in the Antalya area.
AB  - Mediterranean spotted fever, caused by Rickettsia conorii, is a tick-borne
      infection. Serum samples for screening R. conorii antibodies of professionally
      exposed persons in the Antalya region, on the Mediterranean coast of Turkey, were
      analyzed. R. conorii IgG antibodies were detected in 13 of 98 (13.3%) serum
      samples. Mediterranean spotted fever antibodies were found to be positive in 9.4%
      of the men and 15.2% of the women (a total of 13 cases). Only three cases had a
      history of fever and rash.

PMID- 9646111
TI  - HCV genotypes in patients with chronic hepatitis C in Croatia.
AB  - The determination of hepatitis C virus (HCV) genotype is an important
      epidemiological parameter in patients with chronic hepatitis C, while its
      clinical significance is still a matter of debate. The HCV genotypes in a group
      of 203 Croatian patients with chronic hepatitis C were examined. Genotypes were
      correlated to different risk factors, age, duration of the disease, liver
      histology activity and level of viremia. HCV-RNA was detected in each serum by
      means of reverse transcription PCR. Genotypes were determined from the
      amplificate by reverse hybridization in a line probe assay. The level of viremia
      was assessed by branched DNA (bDNA) signal amplification. The most common
      genotype was 1b (61.1% of patients), followed by 3a (26.1%), and 1a (10.8%).
      Other genotypes such as 2a and 4 were only rarely found in our patients (2%).
      Genotype 1b was most commonly acquired via blood transfusion, while genotype 3a
      was strongly related to intravenous drug use. Genotype 1b was associated with
      older age (mean 42.6 vs 29.3 years), longer duration of the disease (mean 6.0 vs
      3.5 years), higher histologic activity score (mean 13.2 vs 10.6) and higher
      viremia (mean 9.06 vs 5.93 Meq/ml) at statistically significant levels (p <
      0.001) when compared to genotype 3a. The prevalence of HCV genotypes follows the
      patterns of southeastern European countries, except for a lower prevalence of
      genotype 2. The observation that genotype 1b is associated with higher viremia
      and more severe liver injury is confirmed.

PMID- 9646112
TI  - Whipple's disease with aortic regurgitation requiring aortic valve replacement.
AB  - Cardiac involvement in Whipple's disease is well established. However, clinical
      consequences beside antibiotic therapy have rarely been reported. Our observation
      of a middle-aged man with increasing dyspnea, fatigue, chest pain, and dizziness
      leading to admission to a cardiology department demonstrates that cardiac
      symptoms may represent the main symptoms in patients with Whipple's disease. The
      diagnosis was not made prior to upper endoscopy, performed because of diarrhea,
      and revealed Whipple's agent now classified as Tropheryma whippelii, which is a
      PAS-positive rod-shaped bacterium in the macrophages of the intestinal lamina
      propria. The aortic valve was replaced after the intestinal symptoms were
      resolved by antibiotic treatment reducing the number of infectious agents in the
      duodenal mucosa. Histological analysis of the aortic valve demonstrated the
      presence of PAS-positive rod shaped material as the most likely cause of aortic
      insufficiency. Five months after valve replacement, the patient had completely
      recovered from intestinal and cardiac symptoms. Still under antibiotic treatment
      16 months later, no more PAS-positive macrophages were detectable in the
      intestinal mucosa.

PMID- 9646113
TI  - Cerebral Dermabacter hominis abscess.
AB  - Dermabacter species are commonly isolated from the skin and other body sites but
      rarely show pathogenicity in humans. A case of Dermabacter hominis cerebral
      abscess is reported which presented as a contrast-enhancing intracranial mass in
      a renal transplant patient.

PMID- 9646115
TI  - Extended spectrum beta-lactamase reactions in Stenotrophomonas maltophilia.

PMID- 9646114
TI  - Disseminated infection with Saccharomyces kluyveri in a patient with AIDS.
AB  - A 47-year-old man with acquired immune deficiency syndrome was found to have
      disseminated Saccharomyces kluyveri infection. The yeast was isolated from blood
      and cerebro-spinal fluid. An autopsy revealed the presence of the microorganism
      in many organs including liver, kidneys, pancreas, spleen, lung, and brain. The
      case confirms a potential pathogenicity of yeasts of the genus Saccharomyces in
      patients with profound immune deficiency, especially in advanced HIV infection.

PMID- 9646116
TI  - Patterns and outcome of septicemia in neutropenic children with cancer in a Greek
      hospital.

PMID- 9646117
TI  - Secondary vulvar and pulmonary mucormycosis in a trauma patient.

PMID- 9646118
TI  - Chronic myelogenous leukemia in an HIV-infected patient.

PMID- 9646119
TI  - Spondylodiscitis by Candida albicans.

PMID- 9646120
TI  - A case of human rabies in The Netherlands.

PMID- 9646121
TI  - Prurigo nodularis in HIV-infected individuals.

PMID- 9646122
TI  - Adverse drug reactions of the new oral antifungal agents--terbinafine,
      fluconazole, and itraconazole.

PMID- 9646123
TI  - Inflammatory perifollicular fibrosis and alopecia.

PMID- 9646124
TI  - Desideratum dermatologica--wanted: an extensive menu of patch test allergens
      available to American dermatologists.

PMID- 9646125
TI  - The significance of Demodex folliculorum density in rosacea.
AB  - BACKGROUND: Demodex folliculorum has been reported in rosacea in a number of
      clinical studies. As the Demodex mite is also present in many healthy
      individuals, it has been suggested that the mite may have a pathogenic role only
      when it is present in high densities. Moreover, some authors have proposed that a
      mite density above 5/cm2 may be a criterion for the diagnosis of inflammatory
      rosacea. In this study, the possible role of D. folliculorum and the importance
      of mite density in rosacea were investigated using a skin surface biopsy
      technique. METHODS: Thirty-eight patients with rosacea and 38 age-and-sex-matched
      healthy subjects entered the study. With the skin surface biopsy technique, we
      obtained samples from three facial sites. We then determined the mite
      positivities, the mean mite counts in both study groups, the mean mite densities
      at each facial site and in the rosacea subgroups, and the mite densities above
      5/cm2. RESULTS: The mean mite count in the rosacea group (6,684) was
      significantly higher than that in controls (2,868; p < 0.05). The cheek was the
      most frequently and heavily infested facial region. Ten rosacea patients and five
      normal subjects had mite densities over 5/cm2; the difference was not
      statistically significant (p > 0.05). CONCLUSIONS: Rosacea is a disease of
      multifactorial origin, and individual properties may modify the severity of the
      inflammatory response to Demodex. We suggest that a certain mite density is not
      an appropriate criterion in the diagnosis of the disease; nevertheless, large
      numbers of D. folliculorum may have an important role in the pathogenesis of
      rosacea, together with other triggering factors.

PMID- 9646126
TI  - Aerobic and anaerobic microbiology of chronic venous ulcers.
AB  - BACKGROUND: The role of bacteria in the pathogenesis of chronic venous leg ulcers
      (CVLU) is unclear. The objective of the study was to establish the aerobic and
      anaerobic bacteriology of CVLU. METHODS: A retrospective review was carried out
      of the clinical and microbiological laboratory records obtained from patients
      with CVLU. Microorganisms were grown from 43 specimens obtained from 41 patients.
      RESULTS: Aerobic or facultative bacteria alone were present in 18 (42%)
      specimens, anaerobic bacteria only in three (7%), and mixed aerobic-anaerobic
      flora in 22 (51%). In total, there were 97 isolates, 64 aerobic or facultative
      and 33 anaerobic, an average of 2.3 isolates per specimen (1.5 aerobes and 0.8
      anaerobes). The predominant aerobic organisms were Staphylococcus aureus (26
      isolates), group D streptococci (5), and Escherichia coli(5). The predominant
      anaerobes were Peptostreptococcus spp. (15), Bacteroides fragilis group (6),
      Propionibacterium acnes (4), and Prevotella spp. (3). CONCLUSIONS: CVLU have a
      polymicrobial aerobic-anaerobic flora.

PMID- 9646127
TI  - Physiologic skin changes during pregnancy: a study of 140 cases.
AB  - BACKGROUND: The endocrine, metabolic, and immunologic changes during pregnancy
      give rise to a number of physiologic cutaneous changes. OBJECTIVE: We evaluated
      140 pregnant women to determine the pattern of pregnancy-induced physiologic skin
      changes in our community. RESULTS: The various changes observed include:
      increased pigmentation (90.7%), striae (77.1%), edema (48.5), melasma (46.4%),
      vascular changes (34.2%), and others. CONCLUSIONS: Pigmentary changes were the
      most common finding, whereas the incidence of vascular changes was quite low (p <
      0.01).

PMID- 9646128
TI  - Eosinophilic ulcer of oral mucosa.

PMID- 9646129
TI  - Cutaneous polyarteritis nodosa: a report of a case associated with melioidosis
      (Burkholderia pseudomallei).

PMID- 9646130
TI  - Eruption of human immunodeficiency virus seroconversion.

PMID- 9646131
TI  - Cutaneous Paecilomyces lilacunis infection in a hospitalized patient taking
      corticosteroids.

PMID- 9646132
TI  - Human gnathostomiasis in Mexico.

PMID- 9646133
TI  - Lymphoscintigraphy in yellow nail syndrome.

PMID- 9646134
TI  - Short treatment schedules of itraconazole in dermatophytosis.

PMID- 9646135
TI  - Topical hydroquinone in the treatment of some hyperpigmentary disorders.

PMID- 9646136
TI  - Butenafine, a fungicidal benzylamine derivative, used once daily for the
      treatment of interdigital tinea pedis.

PMID- 9646137
TI  - Oral treatment schedules for onychomycosis: a study of patient preference.
AB  - BACKGROUND: An improved understanding of patients' attitudes to medication may
      help promote compliance with oral medications for onychomycosis. This study was
      performed to assess patients' preference between continuous and intermittent oral
      treatment schedules for onychomycosis and to determine the reasons underlying the
      selections made. METHODS: Patients were eligible for inclusion if they had
      current onychomycosis and were willing to take oral medication for this
      condition. In a 30-min, face-to-face interview, each patient answered questions
      about four possible treatment schedules for onychomycosis; regimen 1--continuous
      (daily regular intake) for 12 weeks; regimen 2--intermittent 1 week/month for 3
      months (last week of therapy is week 9); regimen 3--intermittent once weekly for
      21 weeks; regimen 4--intermittent 1 week/month for 4 months (last week of therapy
      is week 13). RESULTS: A total of 102 patients from Germany and Spain participated
      in the study. When asked to choose between regimens 1, 2, and 3, 46% of patients
      favored the 9-week intermittent schedule, 42% selected the 12-week continuous
      schedule, and 12% preferred the 21-week intermittent schedule. The preference for
      the 9-week intermittent schedule was more notable among younger patients (< 45
      years), possibly because they are less used to taking regular medication, and
      among Spanish patients, an effect that could not be attributed to age because the
      average age of patients was similar in the participating countries (Germany 47.2
      years; Spain 48.0 years). When the patients who preferred regimen 2 were asked to
      choose between regimens 1, 3, and 4 (both intermittent schedules longer than the
      continuous schedule), most (57%) favored the shortest treatment schedule (regimen
      2). CONCLUSIONS: Overall, patients favored an intermittent schedule lasting 9
      weeks. Treatment duration is the critical factor in determining patients'
      preference for treatment schedules for onychomycosis.

PMID- 9646138
TI  - A questionnaire study on the management of onychomycosis: a Canadian perspective.
AB  - BACKGROUND: Onychomycosis of the toenails is a condition that responds poorly to
      griseofulvin. The introduction of terbinafine in Canada in May 1993 resulted in a
      marked shift in the choice of treatment for pedal onychomycosis. METHODS: A
      questionnaire survey was carried out in 1996 among Canadian dermatologists
      regarding the management of onychomycosis. RESULTS: There were 160 respondents
      from the roughly 350 practicing dermatologists. The dermatologists saw 8 +/- 0.6
      patients per week (average +/- standard error (SE) with suspected or diagnosed
      onychomycosis, with 5 +/- 0.5 patients per week consulting the dermatologists for
      the first time. Most dermatologists performed mycological testing prior to
      starting treatment for onychomycosis. The management options for onychomycosis
      (mean +/- SE) were oral systemic antifungal therapy 51 +/- 3%, no therapy 31 +/-
      3%, and nondrug therapy 9 +/- 2%. The majority of dermatologists (83%) used
      terbinafine as first-line therapy if, indeed, they used oral antifungal agents.
      In contrast, griseofulvin and ketoconazole were used as first-line therapy in 5%
      and 1% of cases, respectively. In Canada, there are no monitoring requirements
      when using oral terbinafine for onychomycosis. Therefore, it is not surprising
      that only 30% of dermatologists performed monitoring with terbinafine. In
      contrast, the frequency of monitoring with griseofulvin and ketoconazole was 40%
      and 80%, respectively. The subset of dermatologists who reported monitoring
      carried it out in only a fraction of their patients: 47%, 53% and 83% for
      terbinafine, griseofulvin, and ketoconazole, respectively. Therefore, the overall
      number of patients in whom regular monitoring was performed was 14.1% 21.2%, and
      71.4% for terbinafine, griseofulvin, and ketoconazole, respectively. The
      perceived cure rates with terbinafine and griseofulvin (mean +/- SE) were 83.7 +/
      1% and 41 +/- 3.1%, respectively. CONCLUSIONS: In May 1996, within three years
      of the introduction of terbinafine to Canada, this agent has become the drug of
      choice for the treatment of pedal onychomycosis (at the time of the survey
      neither itraconazole or fluconazole were approved for onychomycosis). Terbinafine
      has been found to be very effective and safe, and only a minority of
      dermatologists perform regular monitoring with this drug.

PMID- 9646139
TI  - A pilot study on bacterial viability in acne. Assessment using dual flow
      cytometry on microbials present in follicular casts and comedones.
AB  - BACKGROUND: Antibiotic therapy is one of the main methods of acne treatment,
      however, bacterial resistance is on the rise and can affect the treatment
      outcome. Quantitative bacteriologic cultures are the gold standard methodology
      for the assessment of such a problem; however, certain important biological
      aspects remain uncovered. OBJECTIVE: The purpose of this study was to compare the
      antibacterial activity of minocycline and lymecycline in sebaceous follicle
      infundibula and comedones of acne patients. METHOD: We used a recently introduced
      flow cytometric method, allowing a distinction to be made between viable, injured
      (presumably resistant), and dead microorganisms. RESULTS: Minocycline (100 mg)
      proved to be superior to lymecycline (600 mg) in abating the microflora harboring
      in the sebaceous follicles of acne patients. CONCLUSIONS: The dissimilar
      bioavailability and antimicrobial efficacy between the two bacteriostatic agents
      may impart different clinical efficacy.

PMID- 9646140
TI  - Jaipur block in postherpetic neuralgia.
AB  - BACKGROUND: Postherpetic neuralgia, a common sequele to herpes zoster infection,
      is a chronic debilitating problem. The available therapeutic modalities are
      usually ineffective. METHODS: A total of 3960 patients (1326 women and 2634 men;
      age group, 21-84 years), with postherpetic neuralgia as the presenting complaint
      and with pain lasting from 2 months to 5 years, were treated with Jaipur block,
      consisting of local subcutaneous infiltration of 2% xylocaine, 0.5% bupivacaine,
      and 4 mg/mL dexamethasone solution. Patients were followed up at six-weekly
      intervals with subsequent injections given in non-responders. RESULTS: Twenty
      eight per cent of patients obtained complete relief from pain after a single
      injection, another 57% after a second injection, and 11% after a third injection;
      4% of patients did not respond to treatment. The non-responders were either old
      (over 60 years) or had pain lasting for more than 2 years. The response to
      therapy was similar in both sexes. There were 31 left-handed patients in this
      study. Pain was less severe in left-handed patients and they obtained complete
      relief after a single injection. Side-effects including giddiness and sweating
      were seen, occasionally, in a few patients. CONCLUSIONS: Ninety six per cent of
      patients obtained complete relief after the block with a follow-up of up to 19
      years.

PMID- 9646141
TI  - Henri Feulard (1858-1897): the life and works of the secretary of the First
      International Congress of Dermatology.

PMID- 9646142
TI  - Familial occurrence of coexistence of bullous pemphigoid and Sjogren's syndrome.

PMID- 9646143
TI  - Zosteriform skin metastases from breast carcinoma in association with herpes
      zoster.

PMID- 9646144
TI  - Why is there no cobblestoning in lichen sclerosus et atrophicus treated by punch
      grafting?

PMID- 9646145
TI  - Acneform eruption with iodized salt.

PMID- 9646146
TI  - Neurosis and personality disorder in old age. Klaus Bergmann. In Studies in
      Geriatric Psychiatry Eds A. D. Isaacs and F. Post (1978). John Wiley, Chichester,
      pp. 41-75.

PMID- 9646147
TI  - Alcohol related dementia: proposed clinical criteria.
AB  - Current diagnostic criteria for Alcohol Related Dementia (ARD) are based almost
      exclusively on clinical judgment. Moreover, there are no guidelines available to
      assist the clinician or the researcher in distinguishing Alcohol Related Dementia
      from other causes of dementia such as Alzheimer's Disease (AD). However, this
      distinction may have implications for the prognosis and treatment of patients. In
      this article, provisional diagnostic criteria for establishing a diagnosis of
      Alcohol Related Dementia are proposed for further study. The criteria are based
      on the available literature on the relationship between alcohol consumption and
      dementia and were modeled after existing diagnostic criteria for AD and Vascular
      Dementia. Validity of these criteria for distinguishing AD from ARD will require
      further study.

PMID- 9646148
TI  - Religious attitudes and practices of hospitalized medically ill older adults.
AB  - OBJECTIVES: To examine the prevalence of religious beliefs and practices among
      medically ill hospitalized older adults and relate them to social, psychological
      and health characteristics. METHODS AND PROCEDURES: Consecutive patients age 60
      or over admitted to the general medicine cardiology and neurology services of
      Duke University Medical Center were evaluated for participation in a depression
      study. As part of the evaluation, information on religious affiliation, religious
      attendance, private religious activities, intrinsic religiosity and religious
      coping was collected. Demographic, social, psychological and physical health
      characteristics were also assessed. Bivariate and multivariate correlates of
      religious belief and activity were examined using Pearson correlation and linear
      regression. RESULTS: Of the 542 patients evaluated, detailed information on
      religious beliefs and behaviors was collected on 455 cognitively unimpaired
      patients. Over one-half (53.4%) of the sample reported attending religious
      services once per week or more often; 58.7% prayed or studied the Bible daily or
      more often; over 85% of patients held intrinsic religious attitudes; and over 40%
      spontaneously reported that their religious faith was the most important factor
      that enabled them to cope. Religious variables were consistently and
      independently related to race (Black), lower education, higher social support and
      greater life stressors, and religious attendance was associated with less medical
      illness burden. Religious attendance was also related to lower depressive
      symptoms, although the association weakened when other covariates were
      controlled. CONCLUSIONS: Religious practices, attitudes and coping behaviors are
      prevalent among hospitalized medically ill older adults and are related to
      social, psychological and physical health outcomes. Implications for clinical
      practice are discussed.

PMID- 9646149
TI  - The Taps Project 40: quality of care provisions for the elderly mentally ill-
      traditional vs alternative facilities.
AB  - The study evaluates some aspects of care reprovision for psychogeriatric
      patients. Seven hospital wards are compared with four community settings,
      established as part of the reprovision programme for Friern Hospital in London.
      Each facility was assessed for policy and programme, social climate and physical
      characteristics; staff attitudes in regard to their tasks, training needs and job
      satisfaction were also explored. Community settings were superior to hospital
      wards in providing more privacy for the residents and were better equipped with
      physical amenities and safety features. There were relatively small differences
      between the way staff perceived the social climate in community homes and in
      hospital. The former were regarded as encouraging greater independence. Care
      staff in the hospital were more likely to express dissatisfaction with pay,
      working conditions and social status, while community staff were more
      dissatisfied with the quality of cooperation between staff members. Clients
      transferred to Social Services facilities had a higher level of functioning and
      needed less on-site medical care. This was further reflected by the lower
      frequency of nursing care tasks being performed by staff in community facilities.
      Overall, the shift towards a less medical model of care in community-based homes
      appears to be beneficial to psychogeriatric patients, provided that current and
      prospective physical needs of the residents are adequately addressed.

PMID- 9646150
TI  - Total serum homocysteine in senile dementia of Alzheimer type.
AB  - OBJECTIVE: The main hypothesis was that subtle vitamin B12 deficiencies occur
      more commonly in senile dementia of Alzheimer type (SDAT) that in healthy elderly
      individuals, and may be revealed by elevated total serum homocysteine (tHcy). A
      subsidiary hypothesis was that such deficiencies would be nutritionally
      independent as determined by retinol binding protein (RBP). DESIGN: A prospective
      case-controlled survey. SETTING: A Welsh urban psychogeriatric assessment centre
      and local general practice. PATIENTS: Thirty patients, aged 65 or over, seen
      consecutively in 1994 with features compatible with DSM-III-R criteria for
      primary degenerative dementia of Alzheimer type and 30 cognitively intact age
      matched control subjects. MEASURES: Diagnosis was assessed using the CAMDEX.
      Cognitive scores were evaluated with the CAMCOG scale for patients and MMSE
      scores for control subjects. THcy was measured using high performance liquid
      chromatography (HPLC), and RBP assayed by a radial immunodiffusion method.
      RESULTS: Patients had a highly significant elevation of tHcy compared with
      control (p < 0.0001). Multiple regression highlighted the interrelated effects of
      tHcy and total serum cobalamin on cognitive scores. RBP did not differ between
      groups. Macrocytosis was absent, and neutrophil hypersegmentation uncommon, in
      hyperhomocysteinaemic patients. CONCLUSIONS: SDAT patients have significantly
      elevated tHcy. This is independent of RBP determined nutritional status.
      'Classical' haematological changes of cobalamin or folate deficiency are poor
      predictors of tHcy in these patients. Aberrant cobalamin tissue delivery appears
      to contribute to SDAT cognitive decline. Relative contributions of other tHcy
      determinants require further investigation.

PMID- 9646151
TI  - Can depression and depressive symptoms predict mortality at 18-month follow-up in
      acutely medically ill inpatients over the age of 80 years?
AB  - BACKGROUND: The prevalence of depression in acutely medically ill elderly
      inpatients is high. Depression in the elderly is associated with increased
      mortality. METHOD: The association between mortality at 18-month follow-up and
      depression, depressive symptoms and demographic variables at the outset in a
      cohort of acutely medically ill elderly inpatients was examined. RESULTS: The
      mortality at 18-month follow-up was 47%. Depression, depressive symptoms and
      demographic variables were not associated with mortality. CONCLUSION: An
      important explanation of this absence of association between mortality and
      depression may be an artifact due to patient selection designed to resemble
      normal clinical practice.

PMID- 9646152
TI  - Scopolamine-induced cognitive impairment as a predictor of cognitive decline in
      healthy elderly volunteers: a 6-year follow-up.
AB  - OBJECTIVE: To determine if scopolamine-induced cognitive impairment in healthy
      elderly people predicts cognitive decline 6 years later. DESIGN: Prospective
      cohort study. SETTING: Elderly care research unit. PARTICIPANTS: Healthy elderly
      people who were part of a volunteer panel of research subjects. INTERVENTIONS:
      Scopolamine 0.2 mg administered subcutaneously at baseline. MAIN OUTCOME
      MEASURES: Cognitive drug research computerized cognitive testing battery pre- and
      post-scopolamine, with repeat testing over 6 years later. MAIN RESULTS: 16/24
      subjects were retested. Although marked decrements in cognitive functioning were
      seen with scopolamine, there was little change in performance over 6 years, and
      no significant association was seen between scopolamine-induced decrement and
      change over time. CONCLUSIONS: The scopolamine challenge test is not likely to
      play a role in the preclinical diagnosis of Alzheimer's disease.

PMID- 9646153
TI  - Determinants of carer stress in Alzheimer's disease.
AB  - OBJECTIVES: To explore the impact of subgroups and individual symptoms of non
      cognitive disturbance on the carers of Alzheimer's disease patients. DESIGN:
      Cross-sectional study using clinically valid scales to assess patient
      symptomatology and self-report questionnaires to measure carer variables.
      SETTING: Old age psychiatry outreach services in South and Central Manchester.
      SUBJECTS: 100 patients with Alzheimer's disease living at home and their carers.
      MAIN OUTCOME MEASURES: Subjective burden and distress in carers. RESULTS:
      Separate statistical analyses were performed for subgroups and individual
      symptoms of non-cognitive disturbance. For subgroups, multivariate analyses
      identified depression and behavioural disturbances in patients as significant
      predictors of subjective burden in carers. Carer distress was predicted by
      depression, psychosis and cognitive impairments in patients and carer gender. For
      individual symptoms of non-cognitive disturbance, three features of depression in
      patients (mood-related signs, physical signs and behaviour changes), walking
      disruptions and the patient-carer relationship predicted of subjective burden in
      carers. Variance in the level of carer distress was accounted for by sleep
      disruptions, hallucinations and mood-related depressive features in patients and
      carer gender. CONCLUSION: The findings confirm that the non-cognitive features of
      Alzheimer's disease are stressful for carers and indicate specific relationships
      between mood-related and behavioural signs of depression, walking and sleep
      disruptions and hallucinations in patients and adverse carer outcomes. Patient
      depression and the mood-related signs of depression in particular were the most
      consistent and powerful predictors of psychological morbidity in carers.
      Intervention strategies need to identify and target troublesome behaviours in
      patients and aim to either change these behaviours or alter the way carers
      respond to them. Thus, interventions need to be symptoms-rather than service-led
      and are likely to require multidisciplinary and multi-agency approaches.

PMID- 9646154
TI  - Rating depression severity in the elderly physically ill patient: reliability and
      factor structure of the Hamilton and the Montgomery-Asberg Depression Rating
      Scales.
AB  - OBJECTIVES: To assess the appropriateness of the Hamilton Depression Rating Scale
      and the Montgomery-Asberg Depression Rating Scale in depressed elderly physically
      ill patients. DESIGN: Depression scale scores from depressed medical inpatients
      were assessed for internal consistency using Cronbach's alpha, and subjected to
      exploratory principal components factor analyses. SUBJECTS: 100 medical
      inpatients, aged 65 years and over (median age 80.5 years, range 66-99), 74
      female, with Geriatric Mental State Schedule-AGECAT case level diagnoses of
      depression. MATERIALS: The 17-item Hamilton Depression Rating Scale (HDS) and the
      Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: Coefficient alpha for
      the HDS was 0.46; for the MADRS 0.61. Successive deletion of HDS items to
      maximize alpha resulted in a six-item scale (alpha = 0.60); after deletion of
      five MADRS items, alpha was 0.77. Factor analysis of the HDS yielded a four
      factor solution accounting for 57% of the variance, the majority due to anxiety
      and insomnia items; the MADRS yielded a two-factor solution explaining 60% of the
      variance. CONCLUSIONS: Coefficient alpha for both scales is well below the
      minimum necessary for the total score to be used to represent a single construct.
      The HDS appears to be an unreliable measure of depression severity in elderly
      people with physical illness, as the major variance in the scores is due to
      anxiety and insomnia. The MADRS performs better, and with modification may be an
      appropriate measurement of depression severity in this population.

PMID- 9646155
TI  - Late onset of schizophrenia and temporal lobe epilepsy: coincidence or causal?

PMID- 9646156
TI  - The time-related expression of p53 protein in human skin wounds--a quantitative
      immunohistochemical analysis.
AB  - The time-dependent expression of p53 protein during wound healing has been
      investigated by immunochemistry in fibroblastic cells of skin wounds ranging
      between a few minutes and 11 weeks old. When compared to uninjured skin, an
      increased expression of p53 was found earliest in a wound with a postinfliction
      interval of 3 days. The ratio (r) of positively stained cells in relation to the
      total number of fibroblastic cells in the wound area of this specimen was about
      0.2. A considerable increase in the expression of p53 (r > 0.5) was first found
      in a wound aged 8 days and in wounds with postinfliction intervals ranging
      between 3 and 11 weeks, where the ratio of positive cells was between 0.40 and
      0.64. Therefore, it can be calculated that r-values of at least 0.5 indicate a
      postinfliction interval of approximately 1 week or more. Since comparably low
      numbers of positively stained fibroblastic cells were found in specimens with an
      advanced wound duration, reliable information for a forensic wound age estimation
      can only be provided by positive results.

PMID- 9646157
TI  - Cardiac troponin I (cTn I) and the postmortem diagnosis of myocardial infarction.
AB  - In clinical practice several biochemical markers are used for the diagnosis of
      myocardial infarction. Because of its extremely high specificity for myocardial
      damage, cardiac troponin I (cTn I) is frequently used. The aim of this study was
      to evaluate the diagnostic efficacy of postmortem cTn I determinations in
      pericardial fluid and serum and to compare these results with other biochemical
      markers and with structural findings used to diagnose acute myocardial ischaemia.
      We studied 89 cadavers with a mean age of 51.38 +/- 2.04 (SD 19.27 years). Cases
      were allocated to 1 of 4 diagnostic groups depending on the probable intensity of
      myocardial damage and cause of death. In pericardial fluid we obtained
      statistically significant differences for the four biochemical parameters, while
      in serum myosin heavy chains and myoglobin showed statistically significant
      differences. The highest levels of biochemical markers in pericardial fluid were
      observed in subjects who had died from definite myocardial infarction.

PMID- 9646158
TI  - DNA-typing of cellular material on current conductors.
AB  - The examination of deaths due to electricity may require a comparison between
      current marks on the body and the electrodes suspected to have caused them.
      Normally the identification of the responsible electrode is carried out by
      analysing metal traces on the current marks. We however examined the conductor
      for traces of biological material after experimentally produced current marks.
      The surfaces of the conductors were investigated using a low-power macroscope and
      burnt tissue could always be recognised. Subsequently, all electrodes were
      carefully swabbed, extracted with chelex and typed for short tandem repeat
      polymorphisms using PCR. This procedure was successful in all cases. Therefore,
      DNA analysis can be a powerful tool to supplement conventional scene
      reconstruction in cases of deaths due to electricity.

PMID- 9646159
TI  - Tetranucleotide STR system D8S1132: sequencing data and population genetic
      comparisons.
AB  - In the present investigation of the D8S1132 locus 31 selected alleles were
      sequenced. In total there were 9 distinguishable alleles found to increase in
      size by regular 4 bp increments from 134 to 170 bp with a repeat array following
      the pattern (TCTA)n TCA (TCTA)n. One-third of the sequenced alleles exhibited an
      altered repeat sequence TCTG TCTA at the 3' flanking region of the repeat array.
      A nomenclature for the designation of D8S1132 alleles is proposed on the basis of
      this sequence data and in accordance with the ISFH recommendations. The allele
      distribution of the D8S1132 locus has been investigated in three German
      populations (Halle-, Munster-, and Wiesbaden area) with frequencies ranging from
      0.004 to 0.24. No deviation from Hardy-Weinberg equilibrium could be observed.
      The heterozygosity was 0.83 and the discrimination power 0.96 for the Halle
      population.

PMID- 9646160
TI  - Subtyping and characterization of D1S80 alleles in a Japanese population using
      PCR-RFLP.
AB  - In a Japanese population study of the D1S80 locus 24 alleles ranging from allele
      16 to allele43 were analysed using PCR-RFLP. As two repeat units were found to
      contain the restriction cleavage site (CCAGG) for EcoRII, we digested the alleles
      with EcoRII, separated the digested fragments on polyacrylamide gels and stained
      with ethidium bromide. Of the 24 alleles 11 band patterns were identified and
      tentatively labeled E1 to E11. A total of 42 subtypes were detected in a
      population group of 111 unrelated individuals. All samples of allele 18 were of
      the E3 type, while about 60% of the allele24 samples were of the E4 type and
      about 40% were of the E8 type. The third most frequent allele (allele30)
      contained four types, E4, E8, E5 and E6. No deviations from Hardy-Weinberg
      equilibrium were observed. Since this method could differentiate those samples
      which had the same length but different sequences, it is quite useful for
      paternity testing and individual identification.

PMID- 9646161
TI  - Citalopram concentrations in samples from autopsies and living persons.
AB  - Concentrations of citalopram in medicolegal samples from 92 autopsies and 27
      living persons are described. In autopsy cases in which citalopram alone was the
      cause of death, concentrations ranged from 2.0 to 6.2 mg/kg whole blood. In
      autopsy cases in which citalopram together with other substances was considered
      to be the cause of death, the concentrations of citalopram ranged from 0.6 to 5.2
      mg/kg whole blood. In autopsy cases toxic concentrations ranged from 0.4 to 0.9
      mg/kg whole blood and therapeutic concentrations from 0.03 to 0.6 mg/kg whole
      blood. In samples from living persons the concentrations of citalopram in whole
      blood were 0.02 to 0.3 mg/kg.

PMID- 9646162
TI  - Clinical and morphological aspects of death due to liquid nitrogen.
AB  - A 24-year-old student died while filling flasks with liquid nitrogen. The arms,
      legs and back were frozen and the face, ears and neck showed a dark red and livid
      colour with horizontal lines of demarcation. In the electrocardiogram, the heart
      showed asystolia followed by wide ventricular complexes. The patient was
      intubated orally as the situs of the larynx and pharynx showed no pathology
      findings. Cardiopulmonary resuscitation was carried out and terminated after 90
      min. Unfortunately, the body temperature was not measured. The gas analysis of
      venous blood showed metabolic acidosis and oxygen deficiency. The student had
      worked alone with nitrogen, without opening the windows and without a working
      ventilation system. While filling the third flask he lost consciousness. As
      nitrogen does not cause characteristic prodromal signs he laid on the floor and
      was unable to help himself. The liquid nitrogen which was still escaping spread
      over the floor and vaporized. The student died from asphyxia due to oxygen
      deficiency in an atmosphere of nitrogen.

PMID- 9646163
TI  - Suicide with moclobemide and perazine.
AB  - A 51-year-old woman who was diagnosed as suffering from depression was found dead
      in her flat. The autopsy revealed no morphological changes sufficient to explain
      death. Toxicological analysis was performed and the drugs moclobemide (49.9
      mg/l), perazine (1.27 mg/l) and some metabolites were identified in the blood. A
      combined drug intoxication resulting in synergistic effects to cardiovascular
      disorders was proposed as the cause of death.

PMID- 9646164
TI  - Sudden death associated with myxomatous transformation of the mitral valve in an
      8-year-old boy.
AB  - An 8-year-old boy suffered a cardiac arrest while playing soccer. In contrast to
      a similar event at the age of 5 years, resuscitation was not successful. At
      autopsy, the cardiac findings were of a myxomatous transformation of the mitral
      valve with lacerations of the posterior cusp and the left vestibular endocardium
      and left ventricular hypertrophy. Sudden death due to arrhythmias in association
      with a myxomatous mitral valve is a rare event with only about 100 cases
      published world-wide. To our knowledge, the present case probably reports the
      youngest affected individual who died of this pathological condition.

PMID- 9646165
TI  - A case of delayed death after accidental intravenous injection of thrombin.
AB  - A delayed death which occurred after accidental injection of thrombin into the
      right subclavian vein is described. The patient was given heparin intravenously
      after an erroneous intravenous injection of thrombin and died from lobar
      pneumonia 3 months afterwards without any apparently ill effects on the
      circulation of the body except for the brain. At autopsy, however, a large
      thrombus was observed extending continuously from the superior vena cava to the
      pulmonary trunk, via the right atrium and ventricle. From the results it was
      concluded that there was a causal relationship between the inadvertent
      intravenous administration of thrombin and death.

PMID- 9646166
TI  - Car crash after massive ingestion of digoxin and midazolam.
AB  - In a case where a 32-year-old man lost control of his vehicle, urine and blood
      samples were taken 6 h after the crash for toxicological investigations. In the
      hospital, the driver admitted consumption of some drugs, in particular digoxin
      and midazolam just before the crash which corresponded to the results of blood
      analyses. Toxicological findings indicated the presence of digoxin at 12.9 ng/ml
      and midazolam at 7 ng/ml in the blood. These results suggested that at the moment
      of the crash digoxin and midazolam blood levels were in the range of toxic and
      therapeutic concentrations, respectively. Therefore the respective roles of the
      drugs in the impairment of the ability to drive at the moment of the crash is
      discussed.

PMID- 9646167
TI  - Proof of fatal air embolism.
AB  - Venous air embolism is a rare cause of death. Entry of gas into the circulation
      is caused by trauma, mostly surgical or therapeutic, and sometimes resulting from
      criminal intervention. The detection of air embolisms requires special
      precautions during autopsy. An aspirometer has to be used for the detection,
      measurement and storage of gas originating from the heart ventricles. The
      aspirometer has to be filled completely with distilled water containing two drops
      of Tween 80 to reduce the surface tension of the water and to prevent adherence
      of small air bubbles to the wall of the aspirometer. Subsequently the gas has to
      be analysed by gas chromatography. When the results correspond with the main
      criteria defined by Pierucci and Gherson [2] the diagnosis "air embolism" is
      justified. The technique for the detection of air embolism is simple but requires
      a careful procedure which is described in detail.

PMID- 9646168
TI  - Study on the STR TPOX in an Italian and an Austrian population using two
      different primer pairs and three different electrophoretic methods.
AB  - The short tandem repeat TPOX was studied using two different pairs of primers and
      three different electrophoretic methods with the aim of optimizing and
      standardizing the typing conditions for this locus. A genetic population study
      was subsequently conducted on two population samples from Central Italy (151
      individuals) and from Austria (153 individuals) and compared using an R x C
      contingency table. With the aim of using this system for forensic samples,
      differences in sensitivity between the methods utilized were studied and several
      parameters of forensic interest for the two populations (PD, MEC, MEP, pM, PIC)
      were calculated. A new multiplex system for the loci CSF1PO, TPOX and CD4 is also
      presented.

PMID- 9646169
TI  - Y chromosome polymorphisms and haplotypes in west Saxony (Germany).
AB  - In order to apply a set of useful and high polymorphic Y-STRs in paternity
      testing, we performed a population genetic study from Saxony. The allele
      distributions of the systems DYS19, DYS385, DYS389I/II and DYS390 were
      investigated in a sample of 250 unrelated males from the area of Leipzig. PCR
      products were detected using native polyacrylamide gel electrophoresis as well as
      capillary electrophoresis and GenScan Software on the ABI Prism 310 DNA
      sequencer. Haplotype frequency data of 164 different types were obtained which
      show that these four systems are very useful for special cases of paternity and
      forensic stain analysis. In addition several confirmed father-son pairs were
      examined using the paternity cases of the institute. One mutation was found in
      the system DYS390 and sequencing data are presented.

PMID- 9646170
TI  - Metal pins fired from unmodified blank cartridge guns and very small calibre
      weapons--technical and wound ballistic aspects.
AB  - Blank cartridge guns are generally regarded as being harmless and are not
      considered to be firearms in most countries. A comparison of the legal situations
      in Germany and Austria concerning weapons is given. There have been several
      reports of serious injuries and even fatalities due to these weapons. Ballistic
      experiments show that even unmodified blank cartridge guns and very small calibre
      weapons can fire wire nails and can inflict potentially fatal injuries even at
      distances of 50 cm. Two serious injuries inflicted by metal pins fired from a
      blank cartridge gun and a very small calibre weapon are reported. These cases
      suggest that such weapons should also be considered handguns in the legal sense.

PMID- 9646171
TI  - Allele frequency distributions of the polymorphic STR loci HUMVWA, HUMFES,
      HUMF13A01 and the VNTR D1S80 in a Filipino population from Metro Manila.
AB  - Allele frequency distributions at the short tandem repeat (STR) loci HUMVWA,
      HUMFES, HUMF13A01 and of the variable number of tandem repeat (VNTR) locus D1S80
      were determined in a Filipino population from Metro Manila (103 individuals) by
      use of the polymerase chain reaction (PCR) followed by polyacrylamide gel
      electrophoresis (PAGE). The exact test demonstrated that all four loci had no
      deviations from Hardy-Weinberg equilibrium (HWE) with the only reservation that
      the exact test p-value for F13A01 is weak. The discriminating power is 0.82 for
      D1S80, and the expected exclusion chance is 0.85 for F13A01, 0.83 for FES, and
      0.93 for VWA. The observed heterozygosity rates are 0.63 for D1S80, 0.66 for
      F13A01, 0.67 for FES, and 0.80 for VWA. The exact test for independance between
      all loci gave a p-value of 0.0195. This is the first time that Filipino
      population data of DNA loci of forensic importance are reported.

PMID- 9646172
TI  - Self-implanted subcutaneous penile balls--a new phenomenon in western Europe. M.
      A. Rothschild et al. Int J Legal Med (1997) 110: 88-91.

PMID- 9646173
TI  - Interleukin-1, interleukin-1 receptors and interleukin-1 receptor antagonist.
AB  - IL-1 (IL-1 alpha or IL-1 beta) is the prototypic "multifunctional" cytokine.
      Unlike the lymphocyte and colony stimulating growth factors, IL-1 affects nearly
      every cell type, and often in concert with other cytokines or small mediator
      molecules. Although some lymphocyte and colony stimulating growth factors may be
      therapeutically useful, IL-1 is a highly inflammatory cytokine and the margin
      between clinical benefit and unacceptable toxicity in humans is exceedingly
      narrow. In contrast, agents that reduce the production and/or activity of IL-1
      are likely to have an impact on clinical medicine. In support of this concept,
      there is growing evidence that the production and activity of IL-1, particularly
      IL-1 beta, are tightly regulated events as if nature has placed specific "road
      blocks" to reduce the response to IL-1 during disease. In addition to controlling
      gene expression, synthesis and secretion, this regulation extends to surface
      receptors, soluble receptors and a receptor antagonist. Investigators have
      studied how production of the different members of the IL-1 family is controlled,
      the various biological activities of IL-1, the distinct and various functions of
      the IL-1 receptor (IL-1R) family and the complexity of intracellular signaling.
      Mice deficient in IL-1 beta, IL-1 beta converting enzyme (ICE) and IL-1R type I
      have also been studied. Humans have been injected with IL-1 (either IL-1 alpha or
      IL-1 beta) for enhancing bone marrow recovery and for cancer treatment. The IL-1
      specific receptor antagonist (IL-1Ra) has also been tested in clinical trials.

PMID- 9646174
TI  - Interleukin-10 as a regulatory cytokine induced by cellular stress: molecular
      aspects.
AB  - Interleukin-10 is an ubiquitous cytokine which plays a major regulatory role in
      the course of inflammatory responses by downregulating the synthesis of
      cytokines. In this paper, we summarize the major biological properties of IL-10
      and the current knowledge of the molecular mechanisms by which IL-10 inhibits the
      expression of genes encoding proinflammatory cytokines. We then review the
      factors upregulating IL-10 synthesis and we present the concept that IL-10 is a
      stress cytokine produced not only in response to microbial pathogens but also to
      cellular injuries of diverse origins.

PMID- 9646175
TI  - Signaling and functional properties of interleukin-16.
AB  - Interleukin-16 is secreted from a variety of immune cells as a peptide of 17 kDa
      which aggregates into tetrameric form essential for IL-16s direct interaction
      with and cross linking of its receptor, the CD4 antigen. IL-16 stimulation of
      CD4+ cells results in the induction of cell motility, and in addition can
      function as a competence growth factor for CD4+ lymphocytes. These activities
      suggest that IL-16 could play a role in the accumulation and activation of CD4+
      cells recruited to sites of inflammation. Along those lines, IL-16 has been
      identified at sites of inflammation associated with several different disease
      states. Its function as a competence growth factor specifically for CD4+ T cells
      may be useful for immune reconstitution in immunodeficiency diseases such as
      AIDS.

PMID- 9646176
TI  - Interleukin-17.
AB  - The particular interest of IL-17, a homodimeric cytokine of about 32 kDa, is the
      strict requirement for an activation signal to induce its expression from a
      rather restricted set of cells, human memory T cells or mouse alpha beta TCR+CD4
      CD8- thymocytes. In contrast with the tightly controlled expression pattern of
      this gene, the IL-17 receptor, a novel cytokine receptor, is ubiquitously
      distributed but apparently more abundant in spleen and kidney. In addition to its
      capture by the T lymphotropic Herpesvirus Saimiri (HVS), this cytokine is
      inducing the secretion of IL-6, IL-8, PGE2, MCP-1 and G-CSF by adherent cells
      like fibroblasts, keratinocytes, epithelial and endothelial cells. IL-17 is also
      able to induce ICAM-1 surface expression, proliferation of T cells, and growth
      and differentiation of CD34+ human progenitors into neutrophils when cocultured
      in presence of irradiated fibroblasts. In vitro, IL-17 synergizes with other
      proinflammatory signals like TNF alpha for GM-CSF induction, and with CD40-ligand
      for IL-6, IL-8, RANTES and MCP-1 secretion from kidney epithelial cells. In vivo,
      injection of IL-17 induces a neutrophilia, except in IL-6-KO mice. The
      involvement of IL-17 in rejection of kidney graft has also been demonstrated. The
      role of this T cell secreted factor in various inflammatory processes is
      presently investigated.

PMID- 9646177
TI  - TGF-beta: a balancing act.
AB  - Regulation of developmental processes as well as host defense and repair
      mechanisms requires the maintenance of a delicate balance of positive and
      negative regulatory signals. TGF-beta, a molecule known for its many diverse
      activities, can promote or inhibit cell growth and function. Disruption of the
      balance between these opposing activities can contribute to aberrant development,
      malignancy, or pathogenic immune and inflammatory responses. TGF-beta transgenic
      mouse studies highlight the essential function(s) of TGF-beta and its receptors
      and provide insight to potential therapeutic approaches to manipulate TGF-beta
      expression.

PMID- 9646178
TI  - Transcriptional control of cytokine genes.
AB  - With antigen stimulation, cytokine genes are coordinately expressed in T cells.
      However, the optimal signals or helper T cell subset specificity for each
      cytokine gene expression differ. Mechanisms probably exist that transmit
      extracellular signals into the nucleus, thereby coordinately turning on and off
      transcriptional machinery in a signal-specific or cell type-specific manner. We
      compare here the regulation of cytokine genes and discuss possible mechanisms of
      coordinated and differential regulation of cytokine genes.

PMID- 9646179
TI  - Cytokine receptors: structures and signal transduction.
AB  - The characteristic features of cytokines are functional pleiotropy and
      redundancy. Each cytokine is produced by a variety of cell types and acts on a
      wide range of target cells and tissues. Many cytokines have overlapping
      biological activities in the same cells. It was originally thought that each
      cytokine has a specific receptor and a unique signal transduction system.
      However, extensive studies on cytokines and their receptors revealed that many
      cytokines share receptor subunits and signal transduction system, and that
      biological functions of a single cytokine can vary depending on the status of the
      cells. Therefore, it is important to know the structure and function of cytokine
      receptors to understand the pleiotropy and redundancy as well as specificity of
      cytokines. Among signal transduction pathways, recently identified Jak/STAT
      pathway, which connects activation of the receptor complexes and transcription of
      various genes directly, would give us further insights in the mechanisms of
      cytokine action.

PMID- 9646180
TI  - The chronobiology of human cytokine production.
AB  - Cytokine production in human whole blood exhibits diurnal rhythmicity. Peak
      production of the pro-inflammatory cytokines IFN-gamma, TNF-alpha, IL-1 and IL-12
      occurs during the night and early morning at a time when plasma cortisol is
      lowest. The existence of a causal relationship between plasma cortisol and
      production is suggested by the finding that elevation of plasma cortisol within
      the physiological range by the administration of cortisone acetate results in a
      corresponding fall in pro-inflammatory cytokine production. Cortisol may not be
      the only neuroendocrine hormone that entrains cytokine rhythms; other candidates
      include 17-hydroxy progesterone, melatonin and dihydroepiandrostene dione
      (DHEAS). The finding of diurnal cytokine rhythms may be relevant to understanding
      why immuno-inflammatory disorders such as rheumatoid arthritis or asthma exhibit
      night-time or early morning exacerbations and to the optimisation of treatment
      for these disorders. Diurnal rhythmicity of cytokine production also has
      implications for the timing of blood samples drawn for diagnostic T-cell assays.
      Finally, diurnal rhythmicity of immune function suggests that the nature of an
      immune response, for example in response to vaccination, may be modified by the
      time of day of antigen administration and raises the possibility that immune
      responses could be therapeutically manipulated by co-administration of immuno
      regulatory hormones such as glucocorticoids.

PMID- 9646181
TI  - Cytokines in hematopoiesis.
AB  - Hematopoiesis is the process by which mature, functional progeny of the eight
      major lineages of blood cells are produced from a hierarchy of progressively less
      mature progenitor and stem cells. The control of hematopoiesis involves intimate
      cellular interactions between developing blood cells and stromal elements as well
      as regulation by soluble cytokines, that may act locally in the bone marrow
      environment or at remote tissue sites. In excess of twenty cytokines that
      stimulate the production and/or function of hematopoietic cells have now been
      cloned and are available in purified, recombinant form. The colony-stimulating
      factors, erythropoietin and the recently discovered thrombopoietin are key
      regulators of granulocyte/macrophage, erythroid and megakaryocyte/platelet
      production respectively. The activities of these cytokines have been extensively
      studied, both in vitro and in vivo, and recent analysis of mice genetically
      engineered to lack these regulators or their cell surface receptors have provided
      profound insights into their essential physiological roles. These studies have
      culminated in the development of these cytokines as valuable clinical reagents.

PMID- 9646182
TI  - Cytokines and cancer.
AB  - The relationships between cytokines and cancer are multiple and bidirectional. On
      the one hand, cytokines may directly influence carcinogenesis and metastasis by
      modifying the tumor phenotype. On the other hand, during tumor progression,
      modifications of the cytokine expression in the tumor environment may be induced
      by the tumor cells, leading to a state of immunosuppression reflected by low
      cytokine expression in tumor stroma. Cytokines also play a role by stimulating
      the host immune system to generate anti-tumor specific responses. Finally, the
      use of cytokines as anti-tumor agents has led to objective clinical responses in
      about 15-25% of patients with metastatic melanoma or renal cell carcinoma, which
      presents the basis for the development of promising immunotherapeutic approaches
      for cancer therapy.

PMID- 9646183
TI  - Cytokines and chemokines in HIV infection: implications for therapy.
AB  - HIV infection is associated with both a hyperactivity of the immune system and
      decreased immune responses against specific antigens. A similar pattern is
      observed when considering cytokine production in HIV-infected patients. Several
      cytokines are spontaneously produced at an increased level, whereas other
      cytokines playing an important role during cell-mediated immune responses are
      produced at a low level following stimulation. This deregulation of cytokine
      production may participate to the immune deficiency, both by impairing immune
      responses and by accelerating CD4+ T lymphocyte destruction. Chemokine receptors
      have recently been shown to function as coreceptors for the virus, and to govern
      its cellular tropism. Heterogeneous expression of chemokine receptor may
      contribute to differences in infectability as well as in rate of progression of
      the disease between individuals. Better understanding of the role of cytokines
      and chemokines in HIV infection suggests new therapeutic approaches where
      administration of cytokines or cytokine antagonists may allow the immune system
      to function in better conditions, to stimulate antiviral and antiinfectious
      immune defenses, and to limit viral spread.

PMID- 9646184
TI  - Characterization of the haemoglobin-mediated inhibition of the enzymatic activity
      of bovine serum amine oxidase.
AB  - Haemoglobin has been previously identified as responsible for the decreased
      enzymatic activity of copper bovine serum amine oxidase (BSAO) in suspensions of
      human or bovine hemolyzed erythrocytes [Marcocci, L., Pietrangeli, P., Befani,
      O., Mavelli, I., & Mondovi', B. (1991b) Life Chem. Report, 9, 171-177]. This is
      confirmed by present results on bovine methaemoglobin. Bovine globin and horse
      skeletal muscle mioglobin showed a similar inhibiting ability, but neither bovine
      serum albumin nor cytochrome c inhibited BSAO activity under the same
      experimental conditions. The inhibitory effect of bovine haemoglobin was
      dependent on pH only at high buffer ionic strength. It was highest in
      physiological conditions (PBS) where haemoglobin acted as a reversible non
      competitive inhibitor of BSAO activity, with apparent Ki of 0.5 mM at 37 degrees
      C. The inhibition was unaffected by partial BSAO deglycosylation (40% of glucidic
      residues removed) but decreased when haemoglobin lysine groups were derivatised
      using citraconic anhydride. A possible molecular mechanism underlying the
      inhibitory effect is discussed.

PMID- 9646185
TI  - Effects of wortmannin on human neutrophil respiratory burst and phagocytosis.
AB  - Modulation of neutrophil response to naturally occurring stimuli is important to
      avoid host tissue injure. Both soluble and particulate stimuli may induce
      superoxide anion generation in human polymorphonuclear leukocytes. Recently
      wortannin has been shown to inhibit the N-formyl-methionyl-leucyl-phenylalanine
      (fMLP) induced activation of respiratory burst via phosphatidylinositol 3-kinase.
      However no data are available about the effect of the inhibitor on the
      respiratory burst induced by a particulate stimulus. In this paper we studied the
      effect of wortmannin on E. coli induced respiratory burst and phagocytosis by
      flow cytometry, which allows the quantitation of both H2O2 production and
      ingested bacteria in whole blood samples without the need of purification and
      concomitant manipulation of the cells. The effects of worthmannin on fMLP-induced
      chemotaxis was also examined by the under agarose method. Neither the E. coli nor
      the fMLP-induced responses were blocked by wortmannin, suggesting that PI 3
      kinase activity is not required to activate these neutrophil functions. Since it
      is known that the respiratory burst elicited by fMLP is blocked by wortmannin,
      our results suggest that the generation of oxygen radicals is controlled via
      different signal transduction pathways, depending on the agonist used.

PMID- 9646186
TI  - Prolonged in vitro culture modifies the surface lipid composition of murine
      melanoma cell lines.
AB  - Lipid composition of two murine melanoma cell variants (B16, without malignant
      properties and B16-F10, with high metastatic activity), has been examined at
      different stages of growth. The aim of the work was to identify cell surface
      modifications due to the time length of in vitro culture, that could be one
      variable to consider when metastatic potential is studied. Some of the analyzed
      parameters (ganglioside- and glycoprotein-bound neuraminic acid, cholesterol,
      neutral glycolipids, phospholipids, triacylglycerols) undergo statistically
      significant variations at the various passages in B16-F10 line. Fatty acids
      composition of the phospholipidic fraction was changed only at the last observed
      passage (100) in B16 line. No one of the examined parameters justifies the
      ability of B16-F10 cells to invade distant districts and to originate new tumors.
      Probably detailed lipid analysis on cellular subfractions, as already performed
      in this study on total lipid extract of the whole cell, could be a valuable tool
      to identify differences related with metastatic potential.

PMID- 9646187
TI  - Liver transplants in Italy: organizational aspects and inter-regional
      differences.

PMID- 9646188
TI  - Screening for colorectal cancer: the light at the end of the tunnel.

PMID- 9646189
TI  - Should we test for lactose malabsorption?

PMID- 9646190
TI  - Peptic ulcer treatment today--is there a role for maintenance therapy?

PMID- 9646191
TI  - Quality control study of H2 breath testing for the diagnosis of carbohydrate
      malabsorption in Italy. The "Tenue Club" Group.
AB  - BACKGROUND AND AIMS: H2 breath testing is increasingly used in Italy. The aim of
      this multicenter study was to assess the accuracy of this technique in the
      diagnosis of carbohydrate malabsorption. METHODS: An anonymous questionnaire was
      used to collect information about H2 breath testing methods and to design the
      quality control study. Fifteen out of 23 laboratories responded to the
      questionnaire and 12/23 completed the entire study. RESULTS: The survey revealed
      that a large variety of H2 testing methods are employed in Italy, but none have
      been previously tested for accuracy. This prospective study showed that these
      tests fail to identify > 20% of patients with malabsorption. In contrast, a new
      method based on single H2 breath measurement at 6 hours after lactulose ingestion
      and a cutoff value of greater than 5 ppm, had a sensitivity of 92% +/- 4% and a
      specificity of 94% +/- 0.5%. Increasing the cut-off to 10 ppm resulted in a
      sensitivity of 88% +/- 9% and a specificity of 100%. This improved accuracy was
      obtained with a much simpler testing procedure in which only one breath sample is
      analyzed, in contrast to the baseline and multiple subsequent samples that are
      analyzed using the currently employed techniques. CONCLUSIONS: A great
      improvement in the accuracy of the H2 breath test, as well as a considerable
      saving in terms of time and costs, may be possible through the use of a new,
      simplified H2 breath test followed by careful H2 analysis.

PMID- 9646192
TI  - Maintenance therapy with colloidal bismuth subcitrate reduces duodenal ulcer
      relapse.
AB  - AIM: To investigate the efficacy and safety of daily low-dose colloidal bismuth
      subcitrate in reducing duodenal ulcer relapse. DESIGN: Double-blind, double-dummy
      group comparative clinical trial with random allocation. Healing Phase: colloidal
      bismuth subcitrate 240 mg twice daily vs ranitidine 150 mg twice daily for up to
      12 weeks. Maintenance Phase: nightly, colloidal bismuth subcitrate 120 mg vs
      ranitidine 150 mg vs placebo for up to 12 months (high-risk patients received
      active treatment only). ASSESSMENT: clinical, endoscopy, random blood bismuth
      levels (and rapid urease test for Helicobacter pylori in a subgroup). PATIENTS:
      194 with active duodenal ulcer. OUTCOME: Cumulative healing at 12 weeks was 93%
      on colloidal bismuth subcitrate (of 92 patients) and 97% on ranitidine (of 102
      patients). Relapse at 1 year was significantly less on active treatment as
      follows: placebo (50 patients) 60%; ranitidine (71 patients) 21%; colloidal
      bismuth subcitrate (64 patients) 33%. This was independent of the results of the
      rapid urease test which was positive in 78%, 88% and 76% of the patients
      respectively. Treatment was well tolerated. The highest median blood bismuth
      level (mcg/L) was 25 in the healing phase and fluctuated between 6 and 10 in the
      maintenance phase. CONCLUSIONS: Colloidal bismuth subcitrate, 120 mg nightly, is
      effective in reducing duodenal ulcer relapse and is well tolerated.

PMID- 9646193
TI  - Gastrointestinal carcinoid tumours. A population-based study.
AB  - AIM: The aim of this study was to provide further information on the descriptive
      epidemiology of gastrointestinal carcinoids. METHODS: Data was drawn from the
      Tuscany Tumour Registry, a population-based registry active in the province of
      Florence. All the carcinoid tumours reported for the period 1985-1991 in
      gastrointestinal organs were analysed. Incidence, mortality and survival data are
      presented. RESULTS: There were 53 gastrointestinal carcinoid tumours in 29 males
      and 24 females. The site distribution was: 19 small intestine, 8 colon, 7
      appendix, 6 stomach, 6 rectum, 1 large bowel (not specified), and 6 from known
      metastases. The overall age-adjusted incidence rate was 0.42/100,000. At
      diagnosis, 33 carcinoids showed evidence of invasion and/or spreading. Seven
      patients had two independent tumours. As of 31.12.94, nineteen patients had died.
      The overall observed and relative 5-year survival rates were 66.1% and 75.1%,
      respectively. CONCLUSIONS: In the province of Florence, the incidence of
      gastrointestinal carcinoid tumours is low. Probably, this result, is in part due
      to the low autopsy rate. The overall survival rate is quite good, with the best
      prognosis seen for appendiceal carcinoids and the worst for colon and stomach
      carcinoids. 1.9% of the patients had a further tumour diagnosis.

PMID- 9646194
TI  - Clinicopathological features of early gastric cancer in younger versus older
      patients in a high incidence area of northern Italy.
AB  - AIMS: The relationship between the clinicopathological features of early gastric
      cancer and age were analysed in a retrospective study of 168 patients. METHODS:
      168 patients, residents of the Region of Cremona, who had undergone surgery in
      the period 1978 to 1990 for early gastric cancer, were divided into two groups by
      age and compared. Group I (n = 89) consisted of patients less than 65 years of
      age and Group II (n = 79) of patients between 66 and 85 years of age. RESULTS:
      There were no significant differences between the two groups with respect to the
      sex ratio, tumour size, depth of tumour invasion, and 5-year survival rate. Group
      I patients showed more lymph node involvement (p < 0.01), cancer of the diffuse
      histological type (p < 0.01), and cancers located in the gastric body (p < 0.05).
      Conversely, Group II exhibited more cancers of the protruded (p < 0.05) and
      intestinal histological type (p < 0.01), and more adenomatous residue (p < 0.01).
      CONCLUSIONS: Our findings suggest that early gastric cancer may present
      differently in different age groups; persons 65 years of age and older are more
      likely to have early gastric cancer of the slow-growing type than middle-aged
      patients.

PMID- 9646195
TI  - Differential effect of stress on gastric somatostatin, prostaglandin E and
      gastrin release in the rat.
AB  - BACKGROUND: The relationship between gastric mucosal damage induced by stress,
      peptides present in the gastric mucosa and is not clear. Aim of this study was to
      determine whether cold-restraint stress affected the release of gastric
      somatostatin, gastrin and in the isolated perfused stomach preparation. METHODS:
      Male Sprague-Dawley rats were used, 12 cold-restraint stressed and 12 unstressed
      controls. 4 additional unstressed rats were treated with aspirin (100 mg/kg
      p.o.). After 30 minutes, isolated stomachs were perfused for 50 minutes with
      Krebs-Ringer buffer added with isoproterenol or carbamylcholine plus somatostatin
      14 or carbamylcholine alone, somatostatin, gastrin and prostaglandin E2 release
      in the portal vein effluent were measured by radioimmuno-assay. Histology of the
      gastric mucosa was obtained from a further 4 stressed and 4 unstressed rats.
      RESULTS: In the stomach from stressed animals, the somatostatin response to
      isoproterenol and the prostaglandin E2 response to carbamylcholine plus
      somatostatin were significantly lower than in the controls, whereas gastrin
      response to carbamylcholine was enhanced by stress. Treatment with aspirin
      abolished the prostaglandin E2 response to stimulation. Gastric mucosa histology
      from stressed and unstressed animals showed no significant lesions. CONCLUSIONS:
      The inhibition of gastric somatostatin and prostaglandins release coupled to an
      enhanced acid stimulatory influence appear to antidate gastric mucosal injury and
      should play a role in the stress ulcer genesis.

PMID- 9646196
TI  - Intrahepatic expression of c-fos, c-myb and c-myc oncogenes: correlation with
      virus-induced chronic liver disease and response to interferon.
AB  - BACKGROUND & AIMS: Oncogenes were activated in experimental models of hepatocyte
      regeneration. We studied the intrahepatic expression of c-fos, c-myb and c-myc
      protooncogenes in 117 patients with chronic liver disease: 12 with hepatitis B,
      15 HBsAg carriers, 73 with hepatitis C and 17 with non-viral liver damage.
      METHODS: Oncoproteins were detected by indirect immunofluorescence using high
      affinity and monoclonal antibodies. Grade and stage of liver damage were measured
      by numerical score. RESULTS: Nuclear c-fos and/or c-myb were found in 7 (58.3%)
      hepatitis B patients, in 38 (52%) hepatitis C patients, in 1 (6.6%) HBsAg carrier
      (p < 0.004) and in none of the non-viral disease patients (p < 0.0001). In no
      case was c-myc detected. Oncoproteins were correlated with the histological
      activity index (p < 0.0001) and its components: lobular degeneration and
      periportal necrosis (p < 0.0001), fibrosis (p < 0.005) and portal inflammation (p
      < 0.03). Thirty-one chronic hepatitis C patients were treated with alpha-IFN: 9
      out of 14 oncoprotein-positive patients (64%) were non-responders, 5 (36%)
      relapsed and none was a sustained responder. Conversely 9 out of 17 (53%)
      oncoprotein-negative patients, including 3 patients with histologically active
      cirrhosis, showed long-term response (p < 0.005). CONCLUSIONS: Intrahepatic c-fos
      and c-myb were detected in chronic viral hepatitis patients, but not in non-viral
      liver diseases. Their expression correlated with the grade and stage of liver
      disease and with poor response to alpha-IFN.

PMID- 9646197
TI  - Syndromic variability of Wilson's disease in children. Clinical study of 44
      cases.
AB  - BACKGROUND: In children with Wilson's disease, no clinical or laboratory data are
      specific for diagnosis as in adult age. AIM: Clinical aspects and parameters of
      copper metabolism in a large series of pediatric cases are evaluated to establish
      certain criteria for diagnosis and for correct treatment, even in difficult
      cases. METHODS: In 44 children with Wilson's disease, clinical aspects,
      histological features, laboratory parameters and data of copper metabolism have
      been studied. Forty patients, treated with penicillamine, were followed up
      (median 77 months). RESULTS: The 44 cases were classified as: asymptomatic forms
      (nine cases, six of them siblings of affected subjects), chronic hepatitis (23
      cases), hepatocerebral manifestations (four cases), decompensated cirrhosis (six
      cases), fulminant hepatic failure with hemolytic anemia (two cases).
      Ceruloplasmin levels were abnormal in 37 out of 43 tested cases, but normal in
      six (14%) who showed high basal and after penicillamine load urine copper
      excretion and increased hepatic copper content. Urine copper concentration was
      pathological in 35 out of 42 tested cases (83%), but normal in seven patients
      under six years. Hepatic copper levels were very high in all the 20 tested
      patients. Under treatment, 27 children had favourable outcome. One patient showed
      no evolution of disease, seven patients worsened because of non-compliance to the
      therapy (one underwent successful liver transplantation) or severe side effects.
      Five patients with failure died. CONCLUSIONS: Wilson's disease in children may
      present with a broad clinical spectrum, but the liver involvement is by far the
      most prevalent. The early diagnosis, based on clinical suspicion and results of
      copper metabolism investigation (including hepatic copper content evaluation in
      difficult cases) and appropriate treatment can prevent the progression of the
      disease.

PMID- 9646198
TI  - The cardiac evaluation of liver transplant recipients: a single center's
      experience.
AB  - OBJECTIVE AND BACKGROUND: Orthotopic liver transplantation is both a difficult
      and a demanding surgical procedure. It is not unexpected that cardiovascular
      dysfunction is present in some individuals being evaluated for liver
      transplantation. Thus, all potential liver transplant recipients seen at this
      center undergo a full cardiac evaluation prior to being accepted for
      transplantation. The goal of this report was to review the components of the
      cardiovascular evaluation utilized at the Oklahoma Transplantation Institute and
      to determine their overall usefulness as well as the ability of the process to
      identify individuals at high risk for a cardiac misadventure during liver
      transplantation. MATERIALS AND METHODS: Between June 25, 1993 and June 30, 1995,
      a total of 154 consecutive patients with chronic liver disease were evaluated.
      The primary liver disease of each was established utilizing specific serologic
      and biochemical tests, ultrasonographic and abdominal tomographic findings, as
      well as hepatic histology results and hepatic iron and copper level
      determinations. Each liver transplant candidate underwent a full cardiac
      evaluation consisting of the following: nuclear ventriculography to estimate the
      left ventricular ejection fraction (at rest and during exercise), right
      ventricular ejection fraction, cardiac output, stroke volume and cardiac index;
      uptake images using thallium and adenosine to identify foci of cardiac ischemic
      or fixed defects; echocardiography to define the dimensions of the various
      cardiac chambers, wall thicknesses, cardiac contractility and morphology of the
      cardiac valves. Finally, coronary arteriography was performed in 26 patients
      (16.9%) who were suspected of having clinically important coronary artery
      disease. It should be noted that all of the cardiac evaluations were performed by
      a single cardiologist. RESULTS: Eight of the 154 potential liver transplant
      candidates (5.2%) were determined as not being eligible for liver transplantation
      because of an inadequate cardiac status based upon an initial history and
      physical examination. Forty-one of the remaining 146 patients (28.1%) underwent
      liver transplantation. The remaining 105 subjects have not been transplanted for
      reasons not related to the cardiac status. Eight of the 41 (19.5%) transplanted
      patients had a clinically advanced cardiac problem recognized prior to liver
      transplantation. Four of these eight required a specific cardiac intervention
      prior to liver transplantation consisting of coronary bypass surgery (n = 1),
      coronary artery balloon dilation (n = 2) or pericardiectomy (n = 1). The
      remaining four patients required no pretransplant cardiac intervention and were
      transplanted. None of these experienced any cardiac complications during, or in
      the 3 months following, the liver transplant procedure. Only one patient
      experienced a specific postoperative cardiac complication, consisting of an
      episode of high grave A-V block requiring transplant placement of a cardiac
      pacing device. This patient had hemochromatosis. CONCLUSIONS: Based upon this
      experience, it can be concluded that coronary artery disease per se is not an
      absolute contraindication for liver transplantation. With appropriate treatment,
      liver transplantation can be performed safely in individuals with confounding
      cardiac disease. Nuclear ventriculography and echocardiography are essential
      procedures in evaluating potential liver transplant recipients in an effort to
      exclude those with occult cardiomyopathy. Coronary arteriography is indicated
      only in selected cases with evidence of cardiac ischemia or infarction.

PMID- 9646199
TI  - Free radicals and not acetaldehyde influence the circulating levels of
      glutathione after acute or chronic alcohol abuse: in vivo and in vitro studies.
AB  - BACKGROUND: The oxidation of ethanol and acetaldehyde enhances the production of
      various free radicals involved in membrane lipoperoxidation, and decreases
      glutathione levels. AIMS: We evaluated the effects of acute and chronic ethanol
      use in vivo, with or without the administration of S-adenosyl-methionine (SAME, 2
      g I.v.), and the effects of ethanol and acetaldehyde in vitro, on the erythrocyte
      levels of malonyldialdehyde and glutathione, and of its principal synthesizing
      enzymes, gamma-glutamyl-cysteine-synthetase and glutathione-synthetase. METHODS:
      Twelve healthy volunteers (age range 26-44 years, median 32 years) and 20 chronic
      alcohol abusers without liver disease (age range 26-57 years, median 44 years)
      were studied. Malonyldialdehyde was evaluated by thiobarbituric acid; glutathione
      and its enzymes by high performance liquid chromatography using a fluorescent
      detector. RESULTS: In the healthy subjects, an acute load of ethanol induced a
      significant decrease in plasma levels of glutathione, which was inhibited by the
      infusion of S-adenosyl-methionine. In the erythrocytes of alcoholic patients,
      glutathione and glutathione-synthetase were decreased while malonyldialdehyde was
      increased. In vitro, acetaldehyde did not affect either the glutathione or the
      glutathione-related enzyme levels. CONCLUSIONS: Our data suggest that the
      alterations in glutathione metabolism in the erythrocytes of alcoholics may be
      due principally to the production of free radicals, as supported by the high
      levels of malonyldialdehyde observed.

PMID- 9646200
TI  - Clinical value of serum pancreatic enzymes in acute alcohol intoxication and
      acute alcoholic pancreatitis.
AB  - BACKGROUND AND AIMS: The aim of this study was to evaluate the incidence in the
      serum of elevated levels of amylase, pancreatic isoamylase, and lipase in acute
      alcohol intoxication among occasional drinkers and chronic alcoholics, and to
      assess the diagnostic ability of the three enzymes for acute alcoholic
      pancreatitis. PATIENTS AND METHODS: One-hundred and seventeen consecutive
      subjects with acute alcohol intoxication but no abdominal pain (47 occasional
      drinkers, 70 chronic alcoholics), and 17 with acute alcoholic pancreatitis were
      studied. For all subjects serum amylase, pancreatic isoamylase, and lipase were
      determined using commercially available kits. RESULTS: Among occasional drinkers,
      serum amylase levels were abnormally high in 6 subjects (13%), whereas serum
      pancreatic isoamylase and lipase were abnormally high in one, (2%). In chronic
      alcoholics without abdominal pain serum amylase and lipase were abnormally high
      in 10 subjects (14%) but serum pancreatic isoamylase in only 7 (10%). In patients
      with acute alcoholic pancreatitis, serum amylase and pancreatic isoamylase were
      abnormally high in 16 of the 17 patients (94%), whereas serum lipase was
      abnormally high in all. CONCLUSIONS: Chronic alcohol abuse, but not occasional
      alcohol intoxication, may cause pancreatic damage. Amylase, pancreatic isoamylase
      and lipase determinations in the serum are all equally useful in the diagnosis of
      acute alcoholic pancreatitis.

PMID- 9646201
TI  - Percutaneous blind needle biopsy versus combined laparoscopic excisional and
      guided needle biopsy in the diagnosis of liver disorders in pediatric patients.
AB  - AIMS: The authors retrospectively analyzed the results of their experience with
      combined laparoscopic excisional and guided needle biopsy in the determination of
      chronic liver disease in children. PATIENTS AND METHODS: Between January 1986 and
      January 1996, at the Division of Pediatric Surgery of the "Federico II"
      University of Naples, eighty patients underwent laparoscopic liver biopsy to
      evaluate a chronic liver disease. Patient ages ranged between 50 days and 16
      years (mean 5.8 years). There were 41 girls and 39 boys. Fifteen of these
      children (18.7%) were addressed to a surgeon because the previously performed
      percutaneous blind needle biopsy was not sufficiently informative or because the
      specimens were too small to allow chemical or biochemical tissue studies. In
      these 15 patients, we performed a combination of laparoscopic guided needle
      biopsy using a 14-gauge tru-cut needle together with an excisional biopsy on the
      right lobe, using two additional 5-mm trocars. RESULTS AND CONCLUSION: The post
      operative course was uneventful for all the patients. All patients were
      discharged from hospital after 24 hours. A precise histological diagnosis was
      made and biochemical tissue studies were possible after laparoscopic biopsy in
      all 15 children. In our opinion, a combination of laparoscopic-guided needle
      biopsy and laparoscopic excisional biopsy is more reliable than simple biopsy
      alone for the diagnosis of cirrhosis in children with chronic liver disease.

PMID- 9646202
TI  - Idiopathic recurrent pancreatitis successfully treated by hepatic vagotomy.
AB  - Idiopathic recurrent pancreatitis and sphincter of Oddi disorders have been
      increasingly found to be concomitant problems. Treatment of this condition
      requires disruption of the integrity of the sphincter of Oddi. The case of a 16
      year-old girl with sphincter of Oddi motor disorders and idiopathic recurrent
      pancreatitis who was successfully treated with hepatic vagotomy. This result, if
      confirmed, could add to our present knowledge of the physiopathology and
      pathogenesis of sphincter of Oddi motor disorders.

PMID- 9646203
TI  - Small cell carcinoma of the lung presenting as chylous ascites: a unique case.
AB  - A 67-year-old female presenting with a history of weight loss and abdominal
      distension was noted on examination to have ascites. Paracentesis revealed a
      chylous ascites and chest radiography showed a right hilar enlargement with mid
      zone infiltration. Abdominal computed tomography demonstrated retroperitoneal
      lymphadenopathy and biopsy of this showed small cell undifferentiated carcinoma.
      This appears to be the first documented association between metastatic small cell
      carcinoma of the lung and chylous ascites.

PMID- 9646204
TI  - Juvenile polyposis coli and associated anomalies. Review of the literature and
      report of a case associated with hereditary spherocytosis.
AB  - A case of juvenile polyposis associated with hereditary spherocytosis is
      presented. All the anomalies associated with juvenile polyposis coli reported in
      the literature are reviewed. The clinical consequences of such a report are
      discussed along with the different forms of therapy for treating juvenile
      polyposis coli. To our knowledge, this is the first report in the literature of
      juvenile polyposis associated with hereditary spherocytosis.

PMID- 9646205
TI  - Molecular diagnostics in hepatitis C virus infection: clinical applications.
      Scientific Committee--"Tecnologie molecolari nella diagnostica delle epatopatie"
      of the Italian Association for the Study of the Liver-AISF.

PMID- 9646206
TI  - Omeprazole, nitrendipine, famotidine and stress-induced ulcers.

PMID- 9646207
TI  - Caroli's disease: a case report.

PMID- 9646208
TI  - Helicobacter pylori, intestinal metaplasia, cell proliferation and expression of
      oncogenes.

PMID- 9646209
TI  - What do we really know about Helicobacter pylori in gastric ulcer disease?

PMID- 9646210
TI  - Appendectomy is an independent protective factor for ulcerative colitis: results
      of a multicentre case control study. The Italian Group for the Study of the Colon
      and Rectum (GISC)
AB  - BACKGROUND: Different exogenous factors are believed to play a role in the
      pathogenesis of ulcerative colitis. Smoking habits and other risk factors have
      received much attention. It has recently been reported that appendectomy
      decreases the risk of ulcerative colitis. AIM: Aim of the study was to further
      examine the role of appendectomy in ulcerative colitis. METHODS: A large
      multicentre case control study was performed. Cases were all patients with a
      recent new diagnosis of ulcerative colitis (from 1990 to 1994) at participating
      centres. One or two controls attending the orthopaedic and surgical units were
      considered and matched to cases for age (+/- 5 years), sex and year of diagnosis.
      A total of 536 cases and 755 controls were enrolled. Mean age of cases was 37.9
      years (range 2-92). Assessment of exposure was done by examining the clinical
      records and by interview, if necessary. Smoking habits, alcohol consumption, use
      of oral contraceptives, type of occupation and area of residence were also
      recorded. Odds ratio and 95% confidence intervals were calculated by conditional
      logistic regression analysis. RESULTS: Forty-one out of the 536 cases (7.6%) and
      150 out of the 755 controls (19.9%) had been submitted to appendectomy. A total
      of 110 out of 536 cases (20.5%) and 135 out of 753 (17.9%) controls had had
      tonsillectomy. Seven out of 41 cases and 15 out of 755 controls underwent
      appendectomy for recurrent pain. In all ulcerative colitis patients, appendectomy
      had been performed before the onset of disease. When data were adjusted for the
      confounding variables, ulcerative colitis patients were less likely to have had
      appendectomy compared with controls (odds ratio = 0.3, confidence interval = 0.19
      0.48). There was no significant association of ulcerative colitis with
      tonsillectomy (odds ratio = 1.09, confidence interval = 0.76-1.58). The well
      recognized inverse association of ulcerative colitis with cigarette smoking was
      also shown in this study. CONCLUSIONS: The present data emerging from a large
      multicentre study, confirm that appendectomy has a protective role for the
      development of ulcerative colitis.

PMID- 9646211
TI  - Ulcerative colitis and appendectomy. What is the nature of the (negative)
      association?

PMID- 9646212
TI  - Effect of Helicobacter pylori eradication on gastric epithelial proliferation.
      Relationship with ras oncogene p21 expression.
AB  - BACKGROUND: Impaired changes in gastric epithelium proliferation have been
      described in Helicobacter pylori infection, and a progressive increase of
      proliferating cells has been shown with the progression of mucosal lesions. AIMS:
      Purpose of this investigation was to study the effect of eradication on bacterium
      induced proliferative changes, evaluated by the proliferating cell nuclear
      antigen labelling index (PCNA LI) and its relationship to the ras oncoprotein
      p21, involved in early events of gastric carcinogenesis. PATIENTS AND METHODS:
      This retrospective study was performed, before and after therapy, in five
      different groups of patients with progressive stages of Helicobacter pylori
      damage (N: normality; HG: histological gastritis with normal endoscopy; EHG:
      histological gastritis with endoscopic chronic erosions; CIM: complete intestinal
      metaplasia; IIM: incomplete intestinal metaplasia). RESULTS: Six months after
      eradication, a normalization of PCNA LI was observed in the areas of gastritis,
      but not in those of intestinal metaplasia, which showed on unchanged type.
      Moreover, immunohistochemical membrane expression of ras oncoprotein p21 was only
      associated to intestinal metaplasia. The protein was also expressed in the
      cytoplasm in 3 patients with incomplete type. CONCLUSIONS: These results suggest
      that the development of intestinal metaplasia may be associated with an
      alteration in the control of gastric epithelium proliferation and could represent
      an initial stage in gastric carcinogenesis. Nevertheless, further genetic changes
      are necessary for a complete progression to neoplastic disease. A long-term
      follow-up on extension, type, proliferative situation and oncoprotein expression
      in areas of intestinal metaplasia may be helpful to explain whether the present
      data provide new information on the mechanism of Helicobacter pylori induced
      gastric carcinogenesis.

PMID- 9646213
TI  - Helicobacter pylori eradication in the healing and recurrence of benign gastric
      ulcer: a two-year, double-blind, placebo controlled study.
AB  - BACKGROUND: Helicobacter pylori infection is associated with idiopathic gastric
      ulcer in about 90% of the cases, but only a few controlled studies aimed at
      evaluating gastric ulcer healing and the natural history after Helicobacter
      pylori-eradication have been carried out. OBJECTIVE: The aim of the present study
      was to evaluate the efficacy of omeprazole coupled with amoxicillin in the
      eradication of Helicobacter pylori and healing and prevention of gastric ulcer
      recurrence. PATIENTS: Fifty-nine patients with active gastric ulcer were
      randomized under double-blind conditions to receive either omeprazole 20 mg twice
      daily for four weeks plus amoxicillin 3 g daily during the first and second week
      (29 patients, Group A) or omeprazole .20 mg twice daily for 4 weeks plus placebo
      for two weeks (30 patients, Group B). METHODS: Endoscopic studies were carried
      out at the end of the 4 weeks treatment (or after 8 weeks in non-healed patients)
      as well as 2, 6 and 12 months later. A total of 3 biopsies in the antrum, 3 in
      the gastric body and at least seven at the edge of the crater were taken at each
      endoscopic control for exclusion, of malignancy, histological detection of
      Helicobacter pylori and for evaluation of gastric histology according to the
      Sydney system. RESULTS: With intention to treat analysis, the percentage of
      healing after 4 and 8 weeks was 86% and 100% in Group A patients and 86% and 93%
      in Group B, respectively. Two patients dropped out in Group B for non medical
      reasons. The percentage of eradication was 63% in Group A and 7% in Group B.
      During a 12-month follow-up gastric ulcer relapsed in 20/32 (63%) of the
      persistently Helicobacter pylori positive patients. Only two out 20 (10%)
      Helicobacter pylori cured patients showed a gastric ulcer relapse and
      Helicobacter pylori reinfection. Twenty out of 30 patients, still healed after 12
      months, underwent endoscopic control after two years. A gastric ulcer relapse was
      observed in three out of nine (33%) patients with persisting infection after
      treatment. No gastric lesions, but one case of erosive oesophagitis were observed
      in the 11 Helicobacter pylori-eradicated patients. CONCLUSIONS: In our
      experience, Helicobacter pylori eradication does not favour gastric ulcer healing
      but does positively influence the subsequent natural history.

PMID- 9646214
TI  - Total gastrectomy: the influence of preserved duodenal transit and of pouch
      reconstruction on abdominal symptoms, nutrient assimilation, and medico-social
      functioning.
AB  - BACKGROUND/AIMS: The aim of this retrospective study was to establish whether
      patients with different reconstruction after total gastrectomy (duodenal bypass
      without pouch (subgroup Ia, n = 88); duodenal bypass with pouch (subgroup Ib, n =
      27); continuous duodenal transit (subgroup II, n = 27)) differ concerning
      abdominal symptoms, nutrient assimilation, and medico-social functioning.
      METHODS: The 142 patients (49 females, 93 males; mean age 57.2 years, (95%
      confidence interval 55 to 59)) after potentially curative total gastrectomy for
      gastric malignancy 500 days earlier (mean: 95% confidence interval 334 to 666)
      were evaluated for abdominal symptoms, biochemical and haematological parameters,
      endoscopic findings, small intestinal bacterial overgrowth, oro-caecal transit
      time, objective signs of malassimilation, and the degree of medico-social
      functioning. RESULTS: There were no significant differences between the subgroups
      in any of the parameters examined. CONCLUSION: In this study, neither subjective
      nor objective patient data support preference for any single mode of the examined
      reconstructions after total gastrectomy. However, small patient numbers,
      unstandardised reconstruction procedures and a recruitment bias might influence
      these findings.

PMID- 9646215
TI  - Use of a new thickened formula for treatment of symptomatic gastrooesophageal
      reflux in infants.
AB  - BACKGROUND: Paediatricians are familiar with infants complaining of regurgitation
      and emesis from gastrooesophageal reflux. These subjects, usually growing
      satisfactorily and healthy, are affected by "functional" or "symptomatic"
      gastrooesophagel reflux and are treated with posture changes and thickened
      feedings. AIM: To evaluate in infants with symptomatic gastrooesophageal reflux
      the effect of a new formula (Nutrilon AR), containing carob flour/locus bean gum
      as a thickening agent; both clinical features and oesophageal acid exposure were
      evaluated. PATIENTS: Twenty-four infants (age range: 5-11 months; median age: 8
      months; 8 females) presented at our Unit with a history of chronic postprandial
      regurgitation. METHODS: During a 24-hour intraoesophageal pH test a traditional
      formula thickened with rice flour at a concentration of 5% was alternated with
      the formula Nutrilon AR; thereafter infants were randomly allocated to receive,
      for two weeks, either a traditional thickened formula or the new formula, in
      addition to posture changes. RESULTS: Intraoesophageal acid exposure was
      significantly lower in the periods following the new formula than after
      traditional formula; at the end of the treatment period patients receiving the
      new formula had a more significant decrease of both symptomatic score and number
      of episodes of emesis than patients on traditional formula. CONCLUSIONS: The new
      available formula, with the characteristics of a thickened meal, is better than a
      formula, traditionally thickened with added rice flour, in the conservative
      treatment of infants with symptomatic gastrooesophageal reflux.

PMID- 9646216
TI  - Gastrectomy, lack of gastric first pass metabolism of ethanol and alcoholic liver
      disease. Results of a multicentre study.
AB  - BACKGROUND: Some conditions characterized by a loss (anatomical or functional) of
      parietal cells of the gastric antrum, containing an alcohol-dehydrogenase, may
      reduce the first pass metabolism of ethanol at that level and, simultaneously,
      raise its bioavailability. The observation that the first pass metabolism was
      drastically suppressed after gastrectomy would appear to suggest that the latter
      condition represents a risk for the development of liver damage in patients who
      continue to consume alcohol even in a non relevant amount. METHODS: Consecutively
      enrolled in the study were 304 individuals of both sexes aged between 45 and 70
      years of whom 114 gastrectomized and 190 pair-matched control subjects all
      submitted to an Upper Gastrointestinal Endoscopy for whatever disturbance. All
      the patients were diagnosed as having liver disease with routine clinical and
      instrumental means. Information was collected concerning the mean daily alcohol
      intake, both before and after the operation. RESULTS: The overall prevalence of
      hepatic lesions was shown to be higher in the gastrectomized than in the control
      group (42.1% vs 25.8%, p = 0.005). Moreover, referring only to alcohol-related
      hepatic lesions (steatosis, steato-fibrosis and cirrhosis), the prevalence was
      higher in the gastrectomized patients than in the controls (29.8% vs 17.9%, p =
      0.02). As far as concerns alcohol consumption, the gastrectomized group had
      consumed 71 g/day and the control group 39 g/day alcohol per person (p < 0.05) in
      a similar period of time (35 and 33 years, respectively). Also the non alcohol
      related liver damage (especially the viral type) was slightly higher in the
      gastrectomized patients (gastrectomized 12.3% vs control 7.9%, p = ns).
      Accordingly, the percentage of serum markers of viral infection was higher in
      this group (HBs Ag: gastrectomized 3.9% vs control 2.2%, p = ns; anti-HCV:
      gastrectomized 13.5% vs control 5.0%, p = 0.03). Finally, to test the eventual
      damaging effects of gastrectomy alone (excluding ethanol and/or viral infection),
      two groups of patients with a medium to low alcoholic negative assumption (30-60
      g ethanol/day) and no signs of viral infection (HBsAg and anti-HCV negative) were
      extrapolated. In these two selected groups, the prevalence of alcoholic-related
      hepatic lesions were not statistically different (28 gastrectomized 20.3% vs 44
      control 18.4%). CONCLUSIONS: In conclusion, data emerging from investigations on
      the population under study indicate that the alcohol and viral infection appear
      to play a more important role in determining hepatic lesions than
      gastroresection.

PMID- 9646217
TI  - Ten-year incidence and natural history of gallstone disease in a rural population
      of women in central Italy. The Rome Group for the Epidemiology and Prevention of
      Cholelithiasis (GREPCO).
AB  - AIMS: To investigate the incidence, risk factors and natural history of gallstone
      disease, a random sample of females belonging to a rural population was enrolled
      in a ten-year longitudinal study. METHODS: The study has been performed in a
      small town on the hills south of Rome. In 1985, a random sample of 426 females,
      aged 20-69 years, was screened by real-time ultrasonography for gallstones and
      previous cholecystectomy. Screening methods included anthropometry, collection of
      a blood sample and a questionnaire on the occurrence of abdominal symptoms.
      During 1995, all these subjects were invited for a 10-year follow-up examination.
      RESULTS: The overall 10-year incidence of gallstone disease was 6.3% (5.5% of new
      gallstones and 0.8% of cholecystectomies). Only 23.1% of the women with
      gallstones were aware of their condition. More than three quarters (76.9%) had
      not suffered biliary pain. Univariate and multivariate analyses demonstrated a
      positive independent association of new gallstone disease with body mass index
      and parity. Out of the initially asymptomatic gallstone women, 15.4% experienced
      at least one episode of biliary pain, 23.1% were submitted to elective
      cholecystectomy and 61.5% remained asymptomatic. CONCLUSIONS: The study
      demonstrates a high incidence of gallstone disease in women belonging to a rural
      free-living population in Italy and suggests body mass index and parity as
      possible true risk factors. Moreover, it confirms that a remarkable proportion of
      asymptomatic patients become symptomatic and eventually undergo cholecystectomy.

PMID- 9646218
TI  - Complete eradication of hepatitis C virus after interferon treatment for chronic
      hepatitis C.
AB  - BACKGROUND: Alpha-interferon therapy can lead to a persistent biochemical
      response, but discordant opinions have been expressed on the definition of
      sustained response and on the real possibility of complete eradication of
      hepatitis C virus (HCV). AIMS: To define the clinical, virological and histologic
      profiles of the patients with sustained response. PATIENTS: Twenty-eight patients
      with three different biochemical and virological patterns of response to
      interferon therapy (16 sustained responders, 6 responders with relapse and 6 non
      responders) were studied for a follow-up period of 36 months. METHODS: HCV-RNA
      sequences were investigated in serum, peripheral blood mononuclear cells and in
      liver tissue by means of reverse transcriptase-polymerase chain reaction,
      targeted to the 5' non coding region. Viral load in serum was quantified by
      branched-DNA signal amplification. HCV genotypes were evaluated using a line
      probe assay. RESULTS: All sustained responders showed persistent normal ALT
      values and loss of serum HCV-RNA during the treatment and in the entire follow-up
      period. The HCV clearance was also demonstrated in peripheral blood mononuclear
      cells and in liver tissue. Pre-treatment HCV-RNA quantitation showed that
      sustained responders had a significantly lower viral load compared to relapsers
      and non responders (p = 0.005). HCV genotyping showed that patients infected by
      genotypes 2a, 3a were more likely to achieve a sustained response. Interestingly,
      a prolonged response was also observed in the only three patients with pre
      treatment detectable viral load infected by genotype 3a and in patients with
      genotype 1b and low viraemia levels. To assess the histologic outcome following
      HCV eradication, all sustained responders underwent a second liver biopsy in the
      follow-up period (6-18 months). Periportal necrosis and portal inflammation were
      significantly improved. CONCLUSIONS: Our results suggest that persistent loss of
      HCV-RNA in serum, peripheral blood mononuclear cells and liver as well as
      histologic improvement are consistent with the complete HCV eradication even from
      intracellular compartments and from potential extra-hepatic sites of viral
      persistence. Moreover, pre-treatment viral load, HCV infecting genotypes and
      histologic features may influence the clinical outcome of hepatitis C and the
      response to interferon therapy.

PMID- 9646219
TI  - Efficacy of oral ciprofloxacin as selective intestinal decontaminant in
      cirrhosis.
AB  - BACKGROUND: Selective intestinal decontamination has been proposed to prevent
      bacterial infection in cirrhosis. AIMS: To evaluate the efficacy of ciprofloxacin
      as selective intestinal decontaminant. PATIENTS AND METHODS: Quantitative
      microbiological studies on serial faeces were carried out in 15 cirrhotic
      patients. Ciprofloxacin was given orally at the starting dose of 250 mg every 12
      hours for 7 days followed by a single dose of 250 mg/day from day 7 to day 14 and
      125 mg/day for the next 3 weeks. Total stool samples were examined in basal
      conditions and on days 7, 14, 21, 28 and 35 of treatment and 3 and 7 days after
      treatment withdrawal. RESULTS: Gram-negative flora was completely eliminated in
      all patients by ciprofloxacin given at doses of 500 and 250 mg/day. When the drug
      was tapered to 125 mg/day, Escherichia coli reappeared in stools of 7 patients
      (antibiotic-resistant in one patient) and Klebsiella oxytoca in two patients
      (antibiotic-resistant in one patient). Faecal concentration of Group D
      Streptococcus was significantly increased at the end of therapy (basal mean 7.7
      +/- 1.2 log CFU vs post treatment mean 9.6 +/- 0.5 log CFU, p < 0.05) while the
      faecal concentration of anaerobic flora and Candida albicans showed no change.
      CONCLUSIONS: Results of this study demonstrate the efficacy of oral ciprofloxacin
      as a selective intestinal decontaminant and ciprofloxacin 250 mg/day is the
      recommended dose for maintaining Selective Intestinal Decontamination. However,
      the risks of inducing antibiotic resistance in Gram-negative flora and promoting
      overgrowth of Gram-positive flora must be carefully considered in all patients
      chronically treated with oral quinolones.

PMID- 9646220
TI  - Minimal change nephropathy presenting in a patient with primary sclerosing
      cholangitis.
AB  - The association of primary sclerosing cholangitis and renal disease is not
      frequent, and is limited to a few reported cases of immune complex
      glomerulonephritis. We report the case of a 34-year-old patient with sclerosing
      cholangitis diagnosed 5 years earlier, with well preserved liver function and no
      clinical manifestations of cholestasis, who developed minimal change nephropathy.
      During the nephrotic phase of the disease, the peripheral blood lymphocyte count
      was normal, with a relative increase in percent CD4+ and an increase in the CD4+:
      CD8+ ratio. CD4+ cells showed immunoactivation. The HLA-DR expression on T-cells
      was 59%, and 16.5% of CD3+ cells were CD25+. A course of prednisone therapy
      induced long-lasting remission of the nephrotic syndrome. Peripheral blood
      lymphocyte count and subtyping were normal 7 months after prednisone withdrawal.
      We conclude that primary sclerosing cholangitis can be associated with minimal
      change nephropathy; underlying cell-mediated immunity may be the common
      pathogenic mechanism.

PMID- 9646221
TI  - Ocular naevus and hyperaemia with dilation of the conjunctival vessels: an early
      manifestation of Crohn's disease?
AB  - Two cases of male patients with Crohn's disease showing the same neonatal ocular
      abnormality, a sector hyperaemia with dilation of the vessels of the bulbar
      conjunctiva surrounding a naevus close to the limbus, are presented. In both
      cases, this manifestation worsened when Crohn's disease relapsed, and improved
      when the disease went into remission with steroid treatment. In Crohn's disease,
      eye involvement is reported in varying percentages, but the condition discussed
      here does not fit into any of the ocular patterns previously described in this
      disease, and could represent an early manifestation of Crohn's disease.

PMID- 9646222
TI  - Polymerase chain reaction for the detection of HCV-RNA: cryoglobulinaemia as a
      cause for false negative results.
AB  - Polymerase chain reaction is widely used in clinical practice as a reliable assay
      for the detection and quantitation of hepatitis C virus RNA in serum and tissue.
      Due to the high sensitivity of the test, both false positive and false negative
      results can occur. The presence of cryoglobulins in serum samples represents a
      variable that can influence the result of a polymerase chain reaction assay
      leading to false negative results. In cases of hepatitis C virus infection
      associated with cryoglobulinaemia, it is extremely important to very carefully
      process the samples to be tested in order to avoid cryoglobulin precipitation and
      the consequent removal of the virus from the sample.

PMID- 9646223
TI  - Liver targeting of nucleoside analogues coupled to galactosyl terminating
      macromolecules: a new approach to the treatment of a chronic viral hepatitis.
AB  - In order to reduce the extrahepatic side effects of antiviral nucleoside
      analogues in the treatment of chronic viral hepatitis, these drugs are conjugated
      with galactosyl-terminating macromolecules. The conjugates selectively enter
      hepatocytes after interaction of the carrier galactose residues with a receptor
      present in large amounts and high affinity only on these cells. Within
      hepatocytes the conjugates are delivered to lysosomes where enzymes split the
      bond between the carrier and the drug, allowing the latter to become concentrated
      in the liver. The majority of experiments referred to in this paper were
      performed employing a conjugate of lactosaminated human albumin with adenine
      arabinoside monophosphate (ara-AMP), a phosphorylated nucleoside analogue active
      against hepatitis B virus. This conjugate administered for 28 days to patients
      with chronic hepatitis B exerted the same antiviral activity as that of the free
      drug without producing any clinical side effects, including the severe
      neurotoxicity caused by free ara-AMP. This result demonstrates the validity of
      the liver targeting approach which enhances the therapeutic possibilities of
      nucleoside analogues. Coupling to galactosyl terminating carriers may be a way of
      obtaining higher drug concentrations within hepatocytes and permitting the use of
      nucleoside analogues, the administration of which would otherwise be impossible
      due to extrahepatic toxicity.

PMID- 9646224
TI  - A ruptured hepatic artery aneurysm: combined percutaneous and endoscopic
      management.

PMID- 9646225
TI  - Pulmonary hypertension and hepatitis C virus related cirrhosis.

PMID- 9646226
TI  - Ulcerative colitis in Greece: course and prognostic factors in 413 consecutive
      patients.

PMID- 9646227
TI  - Statistical evaluation of 2001 carcinoid cases with metastases, collected from
      literature: a comparative study between ordinary carcinoids and atypical
      varieties.
AB  - This study aimed at obtaining a better understanding of the malignant
      characteristics of carcinoids (gut endocrinomas) of the digestive system. After
      excluding cases with no possible individual identification as for age and sex,
      2001 carcinoid cases with metastases among 5647 of the digestive system
      computerized in the Niigata Registry were thus subject to the present analysis.
      These cases were divided into two groups: [A] 1719 with ordinary carcinoid
      histology and [B] 282 with atypical varieties including argyrophil (endocrine)
      cell carcinomas, small/oat cell carcinomas of endocrine type, composite carcinoid
      adenocarcinoma varieties and other neuroendocrine tumors. In many aspects, a
      comparative analysis demonstrated statistical differences between [A] and [B]:
      average age (55.7 vs 60.1), the rates of metastases (34.4% vs 55.6%), the
      association of carcinoid syndrome (21.4% vs 2.8%), tumor size 20mm or less (42.2%
      vs 22.5%), depth of invasion down to the submucosa (21.6% vs 11.7%) and
      transmural invasion (34.3% vs 47.7%), immunohistochemistry of neuron-specific
      enolase (86.5% vs 66.7%), chromogranin (86.1% vs 67.6%), vasointestinal
      polypeptides, ACTH and alpha-fetoprotein, and the 5-year survival rate (61.4% vs
      17.9%). No statistical differences between these two groups were found in the
      male to female ratio, serotonin activities and Grimelius argyrophilia. Although
      no generally acceptable definite criteria and definition for atypical carcinoid
      varieties have yet established, neoplasias of this category seem to have a wide
      range of histological, histochemical, immunohistochemical, ultrastructural and
      biochemical features that may mostly be placed in between ordinary carcinoids and
      ordinary carcinomas.

PMID- 9646228
TI  - Significance of vascular endothelial growth factor mRNA expression in invasion
      and metastasis of hepatocellular carcinoma.
AB  - Vascular endothelial growth factor (VEGF) is an important mediator of vascular
      development in tumors. We aimed at clarifying the relationship between VEGF mRNA
      expression and invasion or metastasis of hepatocellular carcinoma (HCC). Reverse
      transcript-polymerase chain reaction (RT-PCR) was carried out on surgical
      specimens of 48 patients with HCC. The relative levels of VEGF mRNA expression
      were measured by determining a ratio between PCR products of VEGF and the
      endogenous internal standard gene beta-actin. Expression of VEGF mRNA in tumor
      was found in 76.5% (39/51) of patients, whereas it was 21.69% (11/51) in non
      tumorous liver. The levels of VEGF mRNA expression in tumors with tumorous emboli
      and in poor-encapsulated tumors were higher than that without tumorous emboli and
      in well-encapsulated tumors respectively (p < 0.05 t test). There was no
      significance in the expression of VEGF mRNA between large HCC (diameter > 5cm)
      and small HCC (diameter < or = 5cm) (p > 0.05). VEGF may play an important role
      in the invasion and metastasis of HCC. Angiogenesis in tumor correlates with
      progression of HCC.

PMID- 9646229
TI  - Assessment of methods for primary tissue culture of human breast epithelia.
AB  - A serie of 29 human normal, benign and malignant breast tissues were cultivated
      in an attempt to isolate and propagate primary breast epithelial cells in vitro.
      Explants methodology as well as disaggregation techniques (enzymatic and
      mechanical) were employed to obtain better culture conditions. Cells derived from
      breast malignant tissue were propagated in an appropriate and survived in culture
      for at least 6 months, exhibiting a marked preference to grow in suspension
      (independent anchorage). Tumorigenicity assays in nude mice were performed with
      malignant cells obtained from primary culture cells as well as with cells
      achieved from successive passages. The rate of long time cell survival from
      malignant and non-malignant tissues demonstrated the accuracy of the methodology
      but it also emphasised the need for improving technology to obtain cell lines
      with long survival.

PMID- 9646230
TI  - Viruses in human oral cancers.
AB  - The role of viruses in the etiology of human oral cancer is critically reviewed.
      Available evidences show a positive correlation for human oral cancer with human
      papilloma virus (HPV), herpes simplex virus (HSV) and human herpes virus type-6
      (HHV-6), having strongest association with HPV. These viruses may act alone or in
      combination with other carcinogens in the genesis of head and neck malignancies.

PMID- 9646231
TI  - T-2 toxin affects proliferation of three different neoplastic cell lines.
AB  - The antiproliferative effect of T-2 toxin (T-2) towards mouse melanoma B16 cells,
      human myelogenous leukemia K562 cells, and human cervix carcinoma, HeLa cells,
      was studied. For the first four days of T-2 presence B16 cell survival was
      decreased in dose dependent fashion. However, cell survival after eleven days T-2
      action may be dual: some stimulation of cell growth that was direct function of
      the number of seeded cells per well was observed and cell survival (for the
      highest number of seeded cells) six times greater than control, was noticed at 20
      nM T-2 toxin concentration. A smaller cell growth stimulation (cell survival more
      than 3 times higher than control) was observed with a lower cell number seeded
      per well. Nevertheless, by eleventh day concentrations of T-2 higher than 35 nM
      completely inhibited B16 cell proliferation. The same trend was noticed for T-2
      action towards K562 cells. Treatment of HeLa cells with various T-2
      concentrations led to a marked inhibition of cell survival that was more
      pronounced at the end of 44th or 72nd hour, than after the 20th hour of agent's
      action. ICs50 values obtained in the present work, suggest that B16 cells were
      the most sensitive to T-2 antiproliferative action, while HeLa cells were the
      most resistant. When PBMC were cultured with HeLa cells the antagonism against
      various T-2 concentrations was observed; cell survival determined after 44, or 72
      hours of cells incubation, was less decreased compared to cultures treated with T
      2, or with PBMC only. In addition, it was shown that T-2 and cis-DDP had an
      antagonist effect on HeLa cells survival.

PMID- 9646232
TI  - Influence of tobacco on the labelling of red blood cells and plasma proteins with
      technetium-99m.
AB  - Technetium-99m-labelled red blood cells (RBC) have been used as
      radiopharmaceutical in nuclear medicine. The influence of drug interaction in
      this labelling process has been described along with the biological effects of
      tobacco on the labelling of blood elements with technetium-99m. The labelling of
      RBC and plasma proteins can be decreased in presence of tobacco. This can be due
      to either a direct or indirect effect (reactive oxygen species) of tobacco by (i)
      oxidation of the stannous ion, (ii) possible damages caused in plasma membrane
      and/or (iii) possible chelating action on the stannous and/or pertechnetate ions.

PMID- 9646233
TI  - Esophageal endocrinomas, an extremely rare tumor: a statistical comparative
      evaluation of 28 ordinary carcinoids and 72 atypical variants.
AB  - Esophageal endocrinomas are an extremely rare neoplasm. The present study aimed
      to evaluate multiphasic clinical and pathologic aspects of 100 cases of
      esophageal endocrinomas, consisting of 28 cases of ordinary type carcinoids and
      72 atypical varieties collected from worldwide literature and recorded on
      computer in the Niigata Registry. The evaluation of esophageal endocrinoma cases
      was on most occasions carried out in accordance with a comparison between
      ordinary carcinoids and atypical varieties. Esophageal endocrinomas were
      generally characterized by a preponderance of male patients and an older age
      group. They also exhibited a higher metastasis rate, and a lower incidence of
      carcinoid syndrome than overall endocrinomas of the digestive series. They
      further indicated a probable unfavorable postoperative outcome as compared to
      endocrinomas in most other digestive organs. Ordinary carcinoids of the esophagus
      were characterized by smaller size at detection, lower metastasis rate, and
      better postoperative outcome than the atypical variety group. Because of the
      extremely small number of cases of esophageal endocrinomas, additional case
      reports are in future expected to be satisfactorily documented as a valuable
      record.

PMID- 9646234
TI  - Histopathological study of 110 cystectomy specimens for bladder cancer by an
      original mapping method.
AB  - The management of cystectomy specimens represents the first and most important
      step in the study of bladder cancer and related lesions. We carried out a study
      on 110 patients, applying an original mapping protocol which allowed to determine
      the exact topography of lesions, recognizing even the smallest ones and putting
      in evidence some rare histotype. A prevalence of high-grade, high-stage tumors
      was noted, as well as a remarkable frequency of precancerous lesions, mostly
      found in Brunn's nests. This latter finding could mean that in many cases a flat
      carcinoma becomes invasive within a Brunn's nest rather than in surface
      urothelium. We were also able to accurately evaluate prostatic pathology, finding
      incidental malignant lesions of this gland in 24.2% of the cystectomized males.
      The apparently worst prognosis of the patients who underwent chemotherapy depends
      on the fact that they had grades and stages higher than the untreated subjects.
      In conclusion, we believe that a more extensive sampling of cystectomy specimens
      gives highly reliable prognostic data and represents an unreplaceable tool in
      understanding bladder neoplasms.

PMID- 9646235
TI  - Malignant oncocytoma of major salivary glands. Report of a post-irradiation case.
AB  - The fourth case of malignant oncocytoma arising in the submandibular gland is
      here reported. This tumor arose in a 48-year-old man after radiation exposure, a
      finding never described before for malignant oncocytoma. In addition, several
      regional metastatic lymph nodes were found. The diagnosis was confirmed by
      histochemical and ultrastructural findings. The tumor cells showed easily
      recognizable mucus production and, ultrastructurally, abundant mitochondria,
      intracytoplasmic lumina lined by microvilli and lipid droplets. These last
      features have only seldom been described in malignant oncocytoma. Furthermore,
      the neoplastic cells were alpha-1-antitrypsin positive and S100, thyroglobulin,
      carcinoembryonic antigen, and smooth muscle actin negative. A thorough review of
      the literature is also presented.

PMID- 9646236
TI  - Tropisetron in the prevention of acute nausea and vomiting in patients treated
      with high dose epirubicin.
AB  - Tropisetron is a novel selective antagonist of the type-3 serotonin (5-HT3)
      receptor, with proven efficacy in the control of emesis related to cancer
      treatment. Epirubicin in doses of > 100 mg/m2 has a high emetogenic potential.
      This study was designed to determine whether a single intravenous administration
      of tropisetron could prevent acute nausea and vomiting in patients treated with
      high dose epirubicin. Forty chemotherapy naive breast cancer patients treated
      with epirubicin at a dose of 110 mg/m2 on an outpatient basis were enrolled in
      the study. Tropisetron 5 mg i.v. was used as antiemetic prophylaxis. "On demand"
      treatment with tropisetron 5 mg p.os was used for the rescue of patients who
      failed on the initial i.v. dose. Complete control of acute nausea and vomiting
      had 62.5% (95% C.I. 47.2-77.8), partial control 15% (95% C.I. 3.8-26.2) and 22.5%
      (95% C.I. 9.3-35.7) insufficient control or failure. Headache was the most common
      adverse event reported in 3 patients (7.5%) and constipation in 2 patients (5%).
      Interestingly, patients with a negative experience of nausea and vomiting during
      pregnancy and those treated for metastatic disease, had a better control of
      chemotherapy-induced nausea and vomiting. In conclusion, a single 5 mg i.v. dose
      of tropisetron is safe and effective in preventing acute emesis in patients
      treated with high dose epirubicin.

PMID- 9646237
TI  - Prognostic factors in renal cell carcinoma.
AB  - In this study we evaluated some morphological and clinical prognostic factors in
      166 patients with renal cell carcinoma (RCC). Patients' ages, sex and
      localization of the tumor had no effect on survival. Tumor diameter and the
      weight of the nephrectomy specimen revealed prognostic value. Stage of the tumor,
      especially the presence of metastasis, is the most important prognostic factor
      for RCC (p < 0.001). Tumor grade had prognostic value (p = 0.0146). The survival
      difference between cell types was not significant (p > 0.05). Renal vein
      invasion, the presence of pseudocapsules and tumor in the intravascular space,
      mitotic rate, the presence and the number of lymphocytes and macrophages, along
      with the presence of calcifications had no prognostic value (p > 0.05). The
      presence of necrotic areas was significant (p = 0.0102). The patients with
      "infiltrative growth pattern" showed poorer prognosis than patients with "pushing
      type growth pattern", regardless of the existence of a pseudo capsule (p =
      0.0045).

PMID- 9646238
TI  - Recurrent cutaneous leiomyosarcoma.
AB  - Cutaneous leiomyosarcoma is a rare tumour, accounting for 2.3% to 6.5% of all
      soft tissue sarcomas. The case of a young patient with a cutaneous leiomyosarcoma
      on the right gluteal region is here presented. The lesion misdiagnosed as a
      keloid after primary excision of histiocytoma had a two-year history, had been
      excised twice. The tumour was widely excised, and the wound closed primarily. No
      recurrence or distant metastasis are reported 26 months after the initial
      presentation. Clinical, histological, immunohistochemical features and surgical
      strategies of the reported case are discussed and compared with literature.

PMID- 9646239
TI  - Vulvar hemangiopericytoma. Case report.
AB  - A rare case of a hemangiopericytoma of the vulva, observed in a 55-year old
      woman, is presented. So far, only six cases of this uncommon disease--which
      continues to be a source of uncertainty from both a prognostic and therapeutic
      point of view--have been reported. The case is described along with a review of
      international literature.

PMID- 9646240
TI  - Primary scrotal malignant melanoma. Report of 2 cases and review of the
      literature.
AB  - Tumours involving the scrotum are rare and primary malignant melanoma is among
      the rarest of these lesions. Between 1949 and 1996 only 7 cases have been
      reported. We present two cases of scrotal melanoma. The current recommendations
      and management strategies are discussed on the basis of a review of the
      literature.

PMID- 9646241
TI  - Papillary thyroid carcinoma: considerations on surgical treatment.

PMID- 9646242
TI  - Unexpected thyroid cancer: clinical considerations and therapy.

PMID- 9646243
TI  - Follicular thyroid lesions and risk of malignancy: a new diagnostic
      classification on fine-needle aspiration cytology.

PMID- 9646244
TI  - Immature malignant teratoma of the thyroid gland.

PMID- 9646245
TI  - Diagnostic value of preoperative DNA measurement on FNA in benign and malignant
      thyroid neoplasm.

PMID- 9646246
TI  - Parathyroid functional assessment in patients following total thyroidectomy for
      thyroid malignancies.

PMID- 9646247
TI  - Flow chart for clinical staging of thyroid tumors.

PMID- 9646248
TI  - Follicular neoplasms of the thyroid: diagnostic and operative management.

PMID- 9646249
TI  - Papillary carcinoma in small hypoechoic thyroid nodules: predictive value of echo
      color Doppler evaluation. Preliminary results.

PMID- 9646250
TI  - Mixed squamous and small cell lung carcinoma with separate histologic subtypes in
      eye and phalanx metastases.

PMID- 9646252
TI  - Procedures for the diagnosis of virus particles by electron microscopy.

PMID- 9646251
TI  - Preoperative identification of benign versus malignant thyroid nodules, salivary
      glands nodule and enlarged lymph nodes: preliminary results of a modified fine
      needle biopsy technique.

PMID- 9646253
TI  - Genetic markers in the blood of animals: a historical review.
AB  - In this review an attempt is made to list the most important events in the search
      for genetic markers in the blood of animals. In chronological order, blood
      groups, biochemical polymorphisms, lymphocyte antigens and DNA markers have been
      discovered and used in practice. Of all practical uses, parentage verification
      and exclusion are regarded as the most important, and it can be said with pride
      that the South African Stud Book is as infallible as any other stud book in the
      world.

PMID- 9646254
TI  - The effect of endotoxin and anti-endotoxin serum on synovial fluid parameters in
      the horse.

PMID- 9646255
TI  - Targeted radiotherapy with Sm-153-EDTMP in nine cases of canine primary bone
      tumours.
AB  - Nine dogs with primary bone tumours were treated with Samarium-153-EDTMP (Sm-153
      EDTMP). Conventional treatment protocols were precluded by the size of the dogs
      and the owners' refusal of limb amputation. All the tumours were of the
      appendicular skeleton; 4 were confirmed osteosarcomas. The other 5 tumours were
      radiologically suspect for osteosarcoma. Bone scans were performed on all dogs
      using Technetium-99m-methylene diphosphonate (Tc-99m-MDP) before administration
      of Sm-153-EDTMP. Regions of interest were identified over the contralateral limb
      at the same site as the tumour and counts per pixel were recorded for the tumour
      and contralateral limb and expressed as a ratio. The dogs were given 1 injection
      of 37 MBq/kg (1 mCi/kg) of Sm-153-EDTMP intravenously. Thoracic and primary
      tumour site radiographs were taken at monthly or 2-monthly intervals to monitor
      progression of the primary tumour and search for evidence of metastasis. Two dogs
      showed no response to treatment, with an increase in bone pain, and were
      euthanased within 1 month. In 1 dog, a tumour of the scapula underwent complete
      involution and the dog is considered free of disease at 20 months post Sm-153
      EDTMP treatment. The overall tumourcidal effect of a single dose of Sm-153-EDTMP
      on primary bone tumours was difficult to evaluate in this group of dogs, as, with
      one exception, all the primary tumours progressed over time and the dogs were
      euthanased. Pain control, for which Sm-155-EDTMP is used in man, was not evident,
      except in the dog that responded completely to treatment.

PMID- 9646256
TI  - Stability of cardiodynamic and some blood parameters in the baboon following
      intravenous anaesthesia with ketamine and diazepam.
AB  - The stability of cardiodynamic and some blood parameters during a slow,
      continuous infusion of a combination of ketamine and diazepam is reported.
      Contractility (dP/dt), myocardial relaxation (Tln), left ventricular end
      diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), arterial
      blood pressure and certain blood parameters were assessed in 3 male and 3 female
      juvenile baboons (Papio ursinus). Anaesthesia was induced with 15 mg/kg ketamine
      i.m. and maintained with a continuous i.v. infusion (40-60 ml/h) of ketamine and
      diazepam. The mixture consisted of 2 ml ketamine (100 mg/ml), 2 ml diazepam (5
      mg/ml) and 50 ml saline. A period of 75 +/- 10 min was allowed for preparation of
      the animals, after which lead II of the ECG, femoral artery blood pressure and
      left ventricular pressure were recorded at 15-min intervals for a period of 2 h:
      the total duration of anaesthesia was 195 min. Arterial blood samples were
      analysed at 30-min intervals for blood gases, electrolytes, glucose and insulin.
      Left ventricular parameters were derived from the left ventricular pressure
      curve. Tln, LVSP and LVEDP showed small fluctuations. Contractility decreased (p
      < 0.037) at the 195-min interval. No arrhythmias or ECG changes were seen, while
      blood pressure decreased gradually. Serum calcium concentration decreased and
      blood glucose levels increased gradually over time. Anaesthesia and analgesia
      were sufficient and no other drugs were necessary. The animals appeared sedated
      and dazed 60-80 min after the procedure. A continuous infusion of a combination
      of ketamine and diazepam for a duration of 150 min can provide stable anaesthesia
      for cardiodynamic measurements.

PMID- 9646257
TI  - Psychogenic alopecia in a cat: response to clomipramine.

PMID- 9646258
TI  - Osteitis of the apex of the third phalanx following foot trimming in a dairy cow.
AB  - An adult Ayrshire cow was presented with bilateral hind-limb lameness 5 weeks
      after routine claw trimming. Examination under intravenous regional anaesthesia
      revealed ulceration of the sole at the toe of both the right lateral and left
      medial claws of the hind limbs. Radiographic examination showed osteolysis and
      pathological fractures of the 3rd phalanx of both affected claws. Wooden blocks
      were fixed to the 2 healthy claws and the bone fragments were removed using a
      different technique for each claw. Full recovery followed within 11 weeks. The
      aetiological factors and treatment options for this condition, which was
      considered to be caused primarily by incorrect claw trimming, are discussed.

PMID- 9646259
TI  - Datura seed intoxication in two horses.
AB  - A sunflower-based feed supplement grossly contaminated with the seed of a Datura
      sp. resulted in severe signs of poisoning in 2 horses. One horse died peracutely
      of acute gastric dilatation and rupture following ingestion of the contaminated
      feed. The 2nd horse developed unresponsive paralytic ileus that led to
      euthanasia. Examination of the feed and gastrointestinal contents of both horses
      showed a high proportion of the characteristic Datura sp. seeds. The clinical
      signs and pathology in both cases were consistent with intoxication by the
      parasympatholytic alkaloid components of Datura sp.

PMID- 9646260
TI  - Acute Lantana camara poisoning in a Boer goat kid.
AB  - Acute Lantana camara poisoning in a Boer goat kid is described. The animal was
      part of a flock of boer goats that was introduced from the Kalahari thornveld,
      where the plant does not occur, to an area where the plant grew abundantly. At
      necropsy, the animal was severely icteric, dehydrated and constipated, with
      hepatosis, distention of the gall-bladder and nephrosis, but no skin lesions.
      Histopathological findings of the liver confirmed moderate hepatosis with single
      cell necrosis and bile stasis. The pathology is consistent with that described in
      acute Lantana poisoning in cattle, sheep and goats. The absence of
      photosensitisation may be attributed to relatively mild liver damage, or the
      rapid course of this toxicosis.

PMID- 9646261
TI  - Hyperreninaemic hypoaldosteronism in a dog.
AB  - A 9-year-old male German shepherd dog was evaluated for clinical and clinico
      pathological changes that were suggestive of Addison's disease. On further
      investigation the basal plasma cortisol concentration was high, a normal cortisol
      response to ACTH stimulation occurred, plasma renin activity was elevated and low
      serum aldosterone concentration was present. A diagnosis of hyperreninaemic
      hypoaldosteronism was made. Replacement fludrocortisone resulted in complete
      normalisation of the electrolyte and fluid imbalances. Hyperreninaemic
      hypoaldosteronism has never been reported in the dog.

PMID- 9646264
TI  - [Efficiency of investigators in recruitment of patients for clinical trials:
      apropos of a multinational study].
AB  - BACKGROUND: Performance and efficiency in patient selection are essential for
      conducting clinical trials. Data on these are presented from a multinational
      trial. PATIENTS AND METHODS: A randomized, double-blind, placebo-controlled,
      parallel-group study in asthma, with a screening phase followed after
      randomization by a treatment period, was selected. Number of patients screened
      and randomized by centre and country, centres achieving the minimum recruitment
      (> or = 10 patients randomized), and efficiency of investigators
      (randomized/screened x 100) were determined and compared. RESULTS: 564 patients,
      out of 836 screened, were randomized at 69 centres in 11 countries. Twenty-four
      centres (35%) randomized > or = 10 patients each, accounting for 70% (n = 395) of
      the total number recruited. Efficiency was significantly higher among these "high
      performance" centres (81.4%; p < 0.001; OR, 4.7; CI 95%, 3.4-6.5) than in the
      remaining ones (48.1%). Five countries had > or = 2 "high-performance" centres.
      Efficiency was also significantly higher (p < 0.001) among those (370
      randomized/455 screened, 82.1%) than in the remaining centres of the same
      countries (82/140; 58.6%; OR, 3.0; CI 95%, 2.7-4.7). A relevant number of centres
      (n = 17; 25%) randomized 0-1 patient (7 randomized/58 screened). CONCLUSION: The
      analysis of patient selection in clinical trials showed that a minority of
      centres accounted for most of the patients recruited. Those are not only the most
      productive (more patients randomized) but also the more efficient (better quality
      of screening process).

PMID- 9646265
TI  - [Subtyping panic disorders according to their symptoms].
AB  - BACKGROUND: Panic disorder (PD) is a common illness associated with high levels
      of disability and with a high utilisation of non-psychiatric health services
      which is inefficient in most cases. A better understanding of the clinical
      subtyping of PD may improve diagnosis both in psychiatric and medical settings.
      The present study is aimed at assessing the frequency, factorial grouping and
      comorbidity of PD symptoms in a naturalistic sample of patients. PATIENTS AND
      METHODS: All consecutive cases of PD (n = 442) who contacted with two outpatient
      clinics in Barcelona (Spain) were assessed by two experienced interviewers.
      Assessment instrument included SCID-UP-R interview and inventory of panic
      symptoms based on DSM-III-R. RESULTS: Palpitations (86.7%), shortness of breath
      (76.5%), fear of dying (69.9%) and dizziness (63.6%) were the most frequent and
      intense symptoms reported by the PD patients. The principal component analysis
      revealed four factors which explained the 56% of the variancel
      "cardiorespiratory" (23.2%), "depersonalization-derealization" (15.8%),
      "vestibular" (10%) and "mixed" (7%). CONCLUSIONS: The frequency of presentation
      of symptoms was similar to other studies. However some disimilarities appeared
      that may be attributed to transcultural differences as well as terminological
      problems and the range of symptoms assessed. Factors found in the present study
      support the clinical subtyping of PD in 3 groups characterised by
      cardiorespiratory symptoms and fear of dying, cognitive symptoms
      (depersonalization-derealization) and vestibular symptoms such as dizziness and
      faintness.

PMID- 9646266
TI  - [Interrelationship between the duration of HIV infection, viral load and CD4
      positive lymphocyte count].
AB  - BACKGROUND: The decline in CD4+ lymphocytes occurs at different rates in patients
      with HIV infection. A longer duration of HIV infection and a higher level of
      viral replication, represented by the viral load, are associated with a lower
      CD4+ lymphocyte count. However, the interelationship between these variables is
      still not well known. PATIENTS AND METHODS: 107 HIV-infected patients for whom
      the date of infection was known, were included in a transversal study, in which
      the CD4+ lymphocyte count and the plasma viral load were analysed, the last using
      an isothermal amplification method (NASBA). Patients were not receiving
      antiretroviral drugs or suffered intercurrent infections at the time of the
      study. RESULTS: The mean duration of HIV infection was 8.6 +/- 2.9 years. The
      mean CD4+ lymphocyte count was 366 +/- 264 x 10(6)/l. The mean plasma viraemia
      was 4.3 +/- 0.9 logs. In a linear regression model, the CD4+ lymphocyte count was
      explained in 21.7% of cases by the duration of HIV infection, meanwhile the viral
      load justified up to 36.2 of CD4+ cell variability. When both parameters were
      combined, up to 58.4% of CD4+ lymphocyte values were explained. In this model,
      changes of 1 log in viral load had a 4-fold higher effect on the CD4+ cell count
      than each year of HIV infection. CONCLUSIONS: The duration of HIV infection and,
      particularly the viral load strongly influences the current CD4+ lymphocyte
      count, although other variables should exist (virus with syncytium-inducing
      phenotype, age of the patient and his immunegenetic repertoire) influencing the
      different decline seen in CD4+ T-cells.

PMID- 9646267
TI  - [Menopause and musculoskeletal manifestations. Is there a relationship?].

PMID- 9646268
TI  - [The neonate and nosocomial infection].

PMID- 9646270
TI  - [Hospital libraries in Spain and the need for information by health care
      professionals].

PMID- 9646269
TI  - [Muscular dystrophy due to a mutation in the gene of alpha-sarcoglycan subunit of
      dystrophin associated protein complex].
AB  - Linkage studies have confirmed the existence of clinical an genetic heterogeneity
      among the muscular dystrophies due to adhalin deficiency. We present the
      clinical, histological and genetic characteristics in a case of primary
      adhalinopathy (deficiency of the 50 kD subunit or alpha-sarcoglycan). It was a 19
      years-old woman, born of non consanguineous parents, who shows a long evolution
      myopathy with onset before age 7, a severe evolution and becoming wheelchair
      bound at 10 years. She showed evident calf pseudohypertrophy and serum
      creatinkinase (CK) levels were elevated (40-180 times the standard level). The
      histological pattern showed a destructed fascicular architecture in agreement
      with severe muscular dystrophy, normal staining with anti-dystrophin monoclonal
      antibodies and abnormal staining pattern with anti-adhalin antibodies. The
      molecular study evidenced an homozygous point mutation (Arg-->Cys) at position 77
      of exon 3 of the gene coding for the 50 kD subunit of the alpha-sarcoglycan
      complex localised in chromosome 17. In the light of this case, we suggest a
      revision of the diagnostic orientation in the muscular dystrophies and we review
      the new taxonomy of the limb-girdle muscular dystrophies, remarking the clinical
      signs which could indicate a given genetic locus.

PMID- 9646271
TI  - [Perverted authorship].

PMID- 9646272
TI  - [Evaluation of quality of life in clinical trials].

PMID- 9646273
TI  - [Abuse of the emergency departments by patients. Are there immediate solutions?].

PMID- 9646274
TI  - [Estimation of the prevalence of depression from the daily defined doses of
      antidepressive drugs].

PMID- 9646275
TI  - [Bioavailability of medications].

PMID- 9646276
TI  - [Hydroxycobalamin in the treatment of poisoning by both carbon monoxide and
      cyanide].

PMID- 9646277
TI  - [Limb shaking syndrome triggered by severe anemia in a patient with dissection of
      the internal carotid artery].

PMID- 9646278
TI  - Effects of newly synthesized amino acids containing thiazole residues on
      electrically evoked smooth muscle contractions.
AB  - New amino acids containing thiazole residues have been synthesized and in vitro
      experiments were performed to study their action on neurotransmission in target
      tissues with adrenergic and cholinergic neurotransmission. Acetaminothiazoles,
      structurally related to the novel class, are known to act as H1 agonists,
      therefore, the effects of the newly synthesized Ala- and Pro-thiazole derivatives
      on smooth muscle contractile activity were compared to those of histamine (HA).
      The experiments were carried out on electrically stimulated prostatic part of rat
      and rabbit vasa deferentia and proximal guinea pig ileum. HA had biphasic effect
      on electrically evoked neurogenic contractions of guinea pig ileum, Pro(Thz) had
      a stimulating effect, while Ala(Thz) had no effect. The histamine H1-receptor
      antagonist diphenhydramine inhibited the Pro(Thz)-induced spontaneous contractile
      activity in the longitudinal layer of guinea pig ileum. HA had a biphasic effect
      on electrically induced neurogenic contractions of rat and rabbit vasa deferentia
      while Pro(Thz) and Ala(Thz) inhibited the ES-contractions. The present results
      show that the newly synthesized compounds might affect the electrically evoked
      smooth muscle contractions. Some similarity in the effects of HA and of the new
      substances was observed.

PMID- 9646279
TI  - Clonidine and vasomotion physiology.
AB  - It is known that clonidine exerts a hyperpolarizing action and alpha 2-adrenergic
      activity. The experimental work investigates the conditions under which each
      action of clonidine is developed on vascular smooth muscle. Two parameters were
      studied in vitro on bovine aortic media, Ca2+ uptake and vascular tone. The Ca2+
      uptake measurement was performed by incubating in Krebs' solution small slices of
      the preparation in the presence of 45Ca. Studies on vascular tone were performed
      on deendothelialized bovine aortic rings suspended in Krebs' solution. Low
      concentrations of clonidine (1 nM-1 microM) decrease Ca2+ uptake and relax the
      preparation, indicating dominance of the inhibiting action of clonidine may be
      due to an hyperpolarization. Clonidine 10 microM results in equalization of the
      opposing actions of Ca2+ uptake and vascular tone. When the preparation is
      stimulated by alpha 1-adrenergic against phenylephrine 1 microM, clonidine 1 nM
      10 microM potentates the Ca2+ uptake and vascular contraction in a monophasic
      way, indicating that the depolarizing mechanisms connected with the alpha 1
      adrenergic stimulation totally inhibit the relaxing action of clonidine possibly
      due to hyperpolarization. This action is restricted in the presence of yohimbine
      (alpha 2-adrenergic blocker).

PMID- 9646280
TI  - In vivo antiinfluenza virus activity of Kampo medicine Sho-seiryu-to through
      mucosal immune system.
AB  - The Kampo (Japanese herbal) medicine, Sho-seiryu-to, which has traditionally been
      used for the treatment of colds and bronchial asthma, showed potent antiinfluenza
      A and B virus activity through augmentation of production of antiviral IgA
      antibody in the nasal and bronchoalveolar cavities of mice when administrated
      orally before viral infection. Sho-seiryu-to also showed antiinfluenza virus
      activity against A virus H1N1 subtype infected in aged mice (approximately 6
      months old) with an increase of antiviral IgA antibody in the bronchoalveolar
      wash of the treated mice by similar administration. When mice infected with mouse
      nonadapted influenza A virus H3N2 subtype before 14 days were secondarily
      infected with mouse adapted A/PR/8 (H1N1) virus and administered Sho-seiryu-to
      orally after the second infection, replication of the virus in both nasal and
      bronchoalveolar cavities was significantly inhibited. Sho-seiryu-to had no effect
      on the mice which were not primed with mouse nonadapted virus when administered
      after the infection of mouse-adapted A/PR/8 virus. Oral administration of Sho
      seiryu-to caused increment of viral-specific IgA antibody secreting cells in
      mouse nasal lymphocyte. Sho-seiryu-to also augmented IL-2 receptor beta chain+ T
      cells in Peyer's patch of the infected mice. Sho-seiryu-to also significantly
      reduced viral titer in the nasal washes of the infected ovalbumin-sensitized
      bronchial asthma model mice. Oral administration of Sho-seiryu-to before and
      after vaccination significantly augmented hemagglutination-inhibiting antibody in
      the serum by nasal inoculation of influenza HA vaccine, and significantly
      augmented nasal antiviral IgA antibody and bronchoalveolar and serum antiviral
      IgG antibodies even after secondary vaccination although induction of antiviral
      antibody by intranasal vaccination was insufficient without Sho-seiryu-to. These
      results suggest that Sho-seiryu-to is able to prevent influenza virus infection
      by cross-protection of subtypes of influenza A virus and B virus. Sho-seiryu-to
      is also useful for the treatment of influenza virus infection in hosts with a
      history of influenza virus infection and/or influenza vaccination and allergic
      pulmonary inflammation, such as bronchial asthma, and can be used as an adjuvant
      to nasally inoculated influenza HA vaccine.

PMID- 9646281
TI  - Comparison of effect of [D-Arg2,Sar4]-dermorphin (1-4) and morphine on mouse
      small intestinal transit and electrically evoked contraction of guinea pig ileum.
AB  - [D-Arg2,Sar4]-dermorphin (1-4) [DAS-DER (1-4)] was compared with morphine for the
      capacity to affect mouse gastrointestinal transit and electrically evoked
      contractions of the guinea pig ileum (GPI). A single subcutaneous injection with
      DAS-DER (1-4) and morphine dose-dependently inhibited gastrointestinal transit of
      charcoal in mice. DAS-DER (1-4) with ID50 of 0.053 mg/kg was 26 times more potent
      than morphine with ID50 of 1.38 mg/kg. The inhibitory effects of DAS-DER (1-4)
      and morphine were completely inhibited by pretreatment with 1 mg/kg naloxone, an
      opioid receptor antagonist. The GPI contraction was inhibited by DAS-DER (1-4)
      with an IC50 of 6.9 +/- 0.7 nM and morphine with an IC50 of 295.0 +/- 11.8 nM,
      respectively. These effects were also inhibited by preincubation with naloxone.
      Repeated subcutaneous injections of DAS-DER (1-4) and morphine to guinea pigs
      produced tolerance to the inhibitory effect on electrically evoked contractions
      of GPI. Moreover, a marked cross tolerance was seen in guinea pigs made tolerant
      to DAS-DER (1-4) or morphine. The present study indicates that pharmacological
      profiles of DAS-DER (1-4) as assayed by the gastrointestinal transit and
      stimulated contractions of the GPI were almost similar to that of morphine.

PMID- 9646282
TI  - General pharmacological profile and effects of E-4716, a novel histamine receptor
      blocker, on the central nervous system.
AB  - The general pharmacological profile and effects of E-4716 on the CNS have been
      investigated in comparison with other histamine receptor blockers. In in vitro
      studies with isolated organs and in binding studies on numerous receptors, E-4716
      had no activity even at high concentrations, except for the selective blockade of
      H1 receptors. No activity was observed in pharmacological trials in vivo, such as
      the Irwin test or analgesia induced by phenylbenzoquinone or electroshock,
      suggesting a depressant activity on the CNS. In tests potentiating hypnosis
      induced by barbiturates, benzodiazepines and ethanol in mice, E-4716 always
      showed milder potentiating effects than the other reference drugs. In monkeys, no
      sedating effects were observed at 200 mg/kg, p.o. These results suggest that E
      4716 exhibits good clinical efficacy without any secondary effects.

PMID- 9646283
TI  - Micronization: a method of improving the bioavailability of poorly soluble drugs.
AB  - For poorly soluble drugs, the digestive absorption depends on their rate of
      dissolution. Decreasing the particle size of these drugs improves their rate of
      dissolution. Fine grinding mills are use to micronize powders: either jar mills
      or fluid energy mills. Theses processes were applied to griseofulvin,
      progesterone, spironolactone and diosmin. For each drug, micronization improved
      their digestive absorption, and consequently their bioavailability and clinical
      efficacy.

PMID- 9646284
TI  - Pharmacokinetics of factor VIII in hemophilia A patients assessed by frequency
      response method.
AB  - The frequency response method, having its mathematical underpinnings in the
      theory of linear dynamic systems, was utilized to model pharmacokinetic systems
      describing the fate of factor VIII (F VIII) administered to hemophilia A patients
      before surgery. The pharmacokinetic system was defined on the basis of the
      patient's data in such a way that the injection of F VIII during 5-15 min was
      considered the input, and the corresponding plasma F VIII concentration profile
      consisting of both the injection and post-injection part the output of this
      system. The approach is an alternative to routine procedures based only on
      evaluation of the post-injection part of the F VIII concentration profile. With
      respect to the common sampling schedule of F VIII, simple second-order models
      were found acceptable for all the patients involved in the study. However, in the
      patients whose plasma F VIII concentration profiles did not decrease monotonously
      after the injection, these models failed to approximate secondary peaks
      indicating the presence of time delays in F VIII kinetics. The results obtained
      were discussed with respect to applications of pharmacokinetic models for the
      adjusted dose continuous infusion of F VIII in hemophilia A patients during and
      after surgical interventions.

PMID- 9646285
TI  - Basic and clinical studies on the measurement of tau protein in cerebrospinal
      fluid as a biological marker for Alzheimer's disease and related disorders:
      multicenter study in Japan.
AB  - The development of a diagnostic marker for earlier and more accurate clinical
      diagnosis of Alzheimer's disease (AD) is essential to identify AD patients during
      life unequivocally. The purpose of this study was to investigate the basic
      performance and clinical significance of tau level measurement in the
      cerebrospinal fluid (CSF) using an enzyme-linked immunosorbent assay (ELISA)
      developed by Innogenetics. The ELISA system showed reliable reproducibility and
      good linearity. For clinical studies, the CSF samples from a variety of patients
      (n = 332) were examined. They were classified into the four groups: Alzheimer's
      disease (AD); neurodegenerative disease (ND); cerebrovascular diseases (VD); and
      a neurological control (NC) group. The CSF-tau levels for AD, ND, VD and NC were
      426 +/- 234 pg/ml, 239 +/- 157 pg/ml, 216 +/- 136 pg/ml, and 188 +/- 103 pg/ml,
      respectively. The CSF-tau level of the AD group was significantly higher than
      that of the other groups (p < 0.001). The CSF-tau levels increased during follow
      up. The measurement of the tau level in CSF is shown to be a useful marker to
      confirm a clinical diagnosis of AD.

PMID- 9646286
TI  - Behavioral pharmacology of melatonin.

PMID- 9646287
TI  - Preclinical and clinical behavioral paradigms for testing drugs that affect
      learning and memory processes.

PMID- 9646288
TI  - Effects of zinc and nutritional status on clinical outcomes in head and neck
      cancer.
AB  - The head and neck cancer patient often presents with both protein malnutrition
      and trace element deficiencies. Zinc has been found to be deficient in many head
      and neck cancer patients. In this study, pretreatment zinc status and nutritional
      status (measured by the Prognostic Nutritional Index [PNI]) were correlated with
      clinical outcomes in 47 patients. The patients were followed-up for a median of
      52 mo from the time of enrollment. Our results showed that the tumor size and
      overall stage correlated significantly to zinc status whereas no such correlation
      was seen with PNI, alcohol intake, or smoking in our subjects. The results also
      showed that impaired zinc status was associated with an increased number of
      treatment morbidities, unplanned hospitalizations, and treatment delays (P <
      0.05). Nutritional status was not associated with any studied outcome variable.
      The disease-free interval was highest for the group which had both zinc
      sufficient and nutrition-sufficient status. Although our data do not prove
      conclusively, they do suggest that impaired zinc status at presentation may
      contribute to treatment morbidity, and that for an optimal mean disease-free
      interval, a sufficient zinc and nutritional status is required.

PMID- 9646289
TI  - Experimental infusion phlebitis: tolerance osmolality of peripheral venous
      endothelial cells.
AB  - This study aimed to determine the osmolality that peripheral venous endothelial
      cells can tolerate and to clarify the relationship between tolerance osmolality
      and duration of infusion. Nutrient solutions of 539-917 mOsm/kg, prepared to have
      no acidic effect, were infused into rabbit ear veins, and the veins were examined
      histopathologically. In each experiment of 8-, 12-, or 24-h infusion, the higher
      osmolality solutions caused some phlebitic changes, such as loss of venous
      endothelial cells, inflammatory cell infiltration, and edema; however, the lowest
      osmolality solution caused few changes. Infusion of 120 mL/kg of 814 mOsm/kg
      solution caused phlebitis at 5 or 10 mL.kg-1.h-1, however, the same volume of the
      same solution scarcely caused phlebitis at 15 mL.kg-1.h-1 because of the
      shortened infusion duration. These results suggest that the tolerance osmolality
      of peripheral venous endothelial cells with poor blood flow is about 820 mOsm/kg
      for 8 h, 690 mOsm/kg for 12 h, and 550 mOsm/kg for 24 h, and that the tolerance
      osmolality falls as the duration of infusion increases. In conclusion, hypertonic
      solutions should be infused at as high a rate as is clinically acceptable and
      compatible with nutrient bioavailability because increasing the infusion rate
      reduces the duration of infusion and phlebitis.

PMID- 9646290
TI  - Reduction of gut hypoplasia and cachexia in tumor-bearing rats maintained on
      total parenteral nutrition and treated with peptide YY and clenbuterol.
AB  - Prevention of gut hypoplasia associated with total parenteral nutrition (TPN) was
      investigated in 67 adult male Fisher 344 rats. Mass and protein content of the
      small intestine was reduced by 31% and 39%, respectively, after 7 d of TPN in
      tumor-bearing (TB) rats. Coinfusing peptide YY (PYY; 1 nmol.kg-1.h-1) and
      treating the rats with the anabolic beta-adrenergic agonist, clenbuterol (CLE; 2
      mg.kg-1.d-1), resulted in significant savings in small intestine weight (26%
      increase) and protein (42% increase). Although the colon also exhibited a
      significant decrease in mass (31%), none of the treatment combinations were
      effective in this region of the gut. Histologic analysis of ileum suggested that
      the additive effects of PYY and CLE were due to differential effects of these
      compounds on mucosal and muscular tissues, respectively. This combination of
      treatments also resulted in significant savings (30% increase) in gastrocnemius
      protein, suggesting a reduction in the cachectic response. These results suggest
      that TPN-induced gut hypoplasia and cancer cachexia may be reduced by the proper
      combination of nutritional, hormonal, and pharmacologic treatments. In addition,
      the anabolic effects of various treatments may be additive to counteract TPN
      induced gut atrophy.

PMID- 9646291
TI  - Intestinal adaptation in short bowel syndrome without tube feeding or home
      parenteral nutrition: report of four consecutive cases.
AB  - Because home total parenteral nutrition (TPN) is not available to most of the
      Brazilian population, an alternative treatment for short bowel syndrome was
      evaluated. Four patients ages 40-65 y (mean: 53.75 +/- 10.59), three with
      mesenteric thrombosis, and one with Crohn's disease were studied. The average
      length of the remaining small bowel in these patients was 54.5 +/- 6.4 cm; the
      ileocecal valve was preserved in 3 cases. A progressive step diet was used for
      intestinal adaptation. Administration of pectin was started at the beginning of
      the special oral diet (step 1), followed by medium-chain triacylglycerols (MCTs)
      and complex, nonfermentable sugars (step 2); coconut oil (47% MCTs) and simple
      sugars (step 3); and long-chain triacylglycerols and lactose (step 4). TPN was
      interrupted at step 3 or 4 when the energy content of the diet reached 150% of
      the patient's resting energy expenditure, if serum albumin and weight were stable
      or increasing, and if the frequency, amount, and consistency of stools remained
      unchanged. Nutritional follow-up showed that patients responded well to this
      approach; also, patients returned to their previous professional activities.
      Thus, enteral formulas were not essential for gastrointestinal adaptation. Home
      TPN should not be indicated on the basis of strict criteria, but rather when a
      patient fails to adapt to a progressive, special oral diet.

PMID- 9646292
TI  - The potential role of antioxidant vitamins in preventing cardiovascular diseases
      and cancers.
AB  - Cardiovascular diseases and cancers constitute major public health problems in
      all industrialized countries, where they are the main causes of premature
      mortality. There is a large body of evidence suggesting that free-radical
      production can directly or indirectly play a major role in cellular processes
      implicated in atherosclerosis and carcinogenesis. Here we present mechanistic
      data and results of epidemiologic studies on the relationship between antioxidant
      vitamin intake or biochemical status and the risk of cancer and cardiovascular
      diseases. Most epidemiologic data obtained on this topic were based on an
      observational approach, i.e., ecologic, case-control, or prospective studies. All
      these studies indicate that a high dietary intake or high blood concentrations of
      antioxidant vitamins are associated with a reduced risk of cardiovascular
      diseases and cancer at several common sites. Although the results of these
      studies are convergent, they merely suggest a relationship at the population and
      individual level but do not affirm a causality link. Only intervention studies
      (randomized trials), by specifically changing antioxidant vitamin intake, can
      provide conclusive answers. The apparent discrepancies between the results of
      four recently published trials may be explained by the type of population
      (general or high-risk subjects), the differing doses of supplementation
      (nutritional levels or higher), the number of antioxidants tested (one, two, or
      more), and the type of administration (alone or in balanced association). It thus
      appears that a low risk of pathologies may be related to multiple nutrients
      consumed at nutritional doses and in combination. Optimal effects may be expected
      with a combination of nutrients at levels similar to those found in a healthy
      diet. A single antioxidant vitamin given at high doses in subjects with high risk
      of pathologies (smokers, asbestos-exposed subjects) may not have substantial
      benefits and could even have negative consequences.

PMID- 9646293
TI  - Control of postprandial intestinal motility.

PMID- 9646294
TI  - Aging mechanisms from nematodes to mammals.

PMID- 9646296
TI  - Dietary interventions in noninsulin-dependent diabetes mellitus: new approaches.

PMID- 9646295
TI  - Roles of amylin in diabetes and in regulation of nutrient load.
AB  - In summary, amylin, via its hormonal actions, may be relevant to the treatment of
      both forms of diabetes, and, paradoxically, via its amyloidogenic properties, may
      also be relevant to the pathogenesis of NIDDM. Amylin potently inhibits
      postprandial glucagon secretion. The absence of this action could contribute to
      the hyperglucagonemia and subsequently, excessive endogenous glucose production,
      fasting hyperglycemia, and propensity to ketosis seen in insulinopenic diabetes.
      Restoration of normal glucagon secretion by amylin replacement therapy could
      therefore be therapeutically important in treatment of insulin-dependent diabetes
      mellitus. Amylin potently inhibits gastric emptying. This action is consistent
      with a physiologic role of amylin to regulate carbohydrate absorption. Of
      peptides known to be secreted in response to ingested carbohydrate, only amylin
      and glucagon-like peptide-1 are reported to inhibit gastric emptying at near
      physiologic concentrations, and could therefore participate in nutrient-mediated
      feedback control of carbohydrate release from the stomach. Amylin reduces food
      intake in rodents. This action, which synergizes with a similar action of CCK,
      could reflect a role as short-term peripheral satiety agent. Amylin alone or in
      combination with CCK may be useful in moderating caloric intake in obesity and
      other metabolic disorders. Although insulin has been extensively studied as a
      therapy and as a controller of nutrient storage and metabolism, the role of its
      beta-cell partner, amylin, has been largely unrecognized. In contrast to the
      nutrient disposal and storage role of insulin, amylin appears to more generally
      address the opposite side of the energy balance equation, the assimilation of
      nutrient.

PMID- 9646297
TI  - Use of a reduced-carbohydrate, modified-fat enteral formula for improving
      metabolic control and clinical outcomes in long-term care residents with type 2
      diabetes: results of a pilot trial.
AB  - Physiologic responses of 30 enterally-fed long-term care residents with type 2
      diabetes receiving total nutrition support via either a disease-specific (reduced
      carbohydrate, modified-fat) formula or a standard high-carbohydrate formula for 3
      mo were compared. Objectives of the study included evaluating metabolic response
      (glycemic control and lipids) and clinical outcomes. Thirty-four subjects
      requiring total enteral nutrition support by tube were enrolled in this
      prospectively randomized, double-blind, controlled, parallel group 3-mo pilot
      trial. Thirty were evaluable in that they completed 4 wk. Twenty-seven completed
      all 12 wk. The groups were well-matched for physiologic and demographic
      parameters at baseline. Fasting serum glucose and capillary (fingerstick) glucose
      values demonstrated better control in the disease-specific formula-fed group.
      Serum lipid profiles of this group were similar to or better than those of the
      standard formula-fed group. The amount of insulin administered to insulin-using
      subjects in the disease-specific formula-fed group was consistently less than
      before initiation of the formula, whereas the amount administered was
      consistently higher in the group fed the standard formula. Overall, subjects
      randomized to the disease-specific formula experienced better numerical
      biochemical control and better clinical outcomes when expressed on a numerical
      and percentage basis. These included surrogate markers of diabetes control such
      as serum glucose and glycohemoglobin, as well as clinical outcomes such as
      incidence of infections and pressure ulcers. These findings confirm that the
      disease-specific formula provides better glycemic control, poses no risk to
      lipoprotein metabolism, and provides for better clinical outcomes.

PMID- 9646298
TI  - Preparing dietetic professionals for practice in the 21st century: how can
      educational programs respond to changes in health care?

PMID- 9646299
TI  - Early enteral nutrition in surgical patients.
AB  - There is increasing evidence that delivery of nutrients via the gastrointestinal
      tract reduces the septic morbidity in severely injured patients. This article
      reviews the most current data and also reviews the importance of the gut
      associated lymphoid tissue as an important factor in maintaining the host
      defenses.

PMID- 9646300
TI  - Nutritional modulation of immunity and the inflammatory response.
AB  - The metabolic derangements of the injured or stressed patient are governed by
      multiple factors that partially include the severity of insult, preexisting
      illnesses, available energy reserves, and appropriateness of intervention. The
      normal response to injury is further characterized by the release of
      proinflammatory and antiinflammatory mediators that exert potent effects on
      cellular and organ function. Although brief periods of starvation and catabolism
      are tolerable in otherwise healthy individuals, protracted nutritional
      deprivation can manifest as immunocompromise, irreversible organ injury, and late
      mortality. Moreover, patients with severe injuries or preexisting illnesses who
      exhibit exaggerated inflammatory responses may be further predisposed to such
      deleterious consequences following the insult. The optimal supply of appropriate
      nutrients and substrates in such circumstances has often been championed as a
      necessary means of restoring proper cellular metabolism, wound healing, immune
      competence, and proper organ function. However, much debate surrounds the present
      efficacy of nutritional therapy in modulating the immune response associated with
      injury and stress. This article seeks to assess the merits of nutritional
      therapeutics in the injured patient through available biological and clinical
      evidence.

PMID- 9646301
TI  - n-3 versus n-6 polyunsaturated fatty acids in critical illness.
AB  - The effects of n-6 and n-3 polyunsaturated fatty acids (PUFA) on protein
      metabolism, cell-mediated immunity, and production of cytokines and prostanoids
      were studied in experimental animals and patients with esophageal cancer. In the
      experimental study using a rat burn model, n-6 PUFA increased serum interleukin-6
      (IL-6) and tumor necrosis factor (TNF), alpha (P < 0.05), and decreased nitrogen
      balance (NB) (P < 0.05), when compared with a fat-free control. But addition of n
      3 PUFA reduced TNF-alpha and IL-10 (P < 0.05) and improved NB (P < 0.05).
      Suppressed delayed type hypersensitivity (DTH) induced by burn injury, which was
      not influenced by n-6 PUFA, was significantly improved by the administration of n
      3 PUFA. n-6 PUFA tended to increase, and n-3 PUFA significantly decreased the
      endotoxin translocation. DTH, granulocyte-macrophage colony-stimulating factor,
      and eicosapentaenoic acid (EPA) content increased proportionately with the
      intravenous dose of fish oil emulsion. The effects of n-6 and n-3 PUFA were
      studied in the patients who underwent surgery for esophageal cancer. In the group
      of patients fed by total parenteral nutrition with soybean oil emulsion, the
      serum IL-6 significantly increased at 2 and 6 h after operation (P < 0.05).
      Oral/enteral supplementation of EPA ethyl ester (1.8 g/d) significantly reduced
      the postoperative IL-6 production (P < 0.05 at 1, 2, and 6 h after operation),
      and improved cell-mediated immune function 3 wk after operation (P = 0.05).
      During the chemoradiation therapy, cell-mediated immune function was improved
      significantly in the patients fed enterally with EPA ethyl ester (n = 5), when
      compared with the patients without EPA (n = 14).

PMID- 9646302
TI  - Anabolic agents in trauma and sepsis: repleting body mass and function.
AB  - Both growth hormone (GH) and insulin-like growth factor 1 (IGF-1) are potent
      anabolic agents. Exogenous GH improves nitrogen metabolism in patients undergoing
      surgery; however, the anabolic effects of GH in cases of multiple injury, burn,
      and sepsis are equivocal. Moreover, few data are available concerning the effects
      of GH in organ failures. Exogenous IGF-1 attenuates catabolism in animal trauma
      models. A clinical trial, however, did not confirm the anabolic actions of IGF-1.
      Further knowledge of the interaction between the GH/IGF-1 axis in critical
      illness is essential for GH and IGF-1 therapy. Theoretically, the improved
      nitrogen metabolism achieved with exogenous anabolic agents may provide
      functional benefits. However, only a few studies have confirmed the beneficial
      effects of GH on body function in trauma and sepsis. GH treatment decreases the
      postoperative depression of hand grip strength. GH also stimulates wound healing.
      Both GH and IGF-1 exert their effects on immune system, suggesting that these
      anabolic agents are potentially beneficial for the prevention and treatment of
      sepsis. On the contrary, inhibition of polymorphonuclear neutrophil apoptosis and
      the potentiation of PMNs by GH may have harmful effects on the systemic
      responses. Further studies are required to determine the safety and clinical
      benefits of GH administration in critical illness.

PMID- 9646303
TI  - Implications of critical illness, injury, and sepsis on lean body mass and
      nutritional needs.

PMID- 9646304
TI  - Interleukin 8 can affect inner ear function.
AB  - The chemokine interleukin 8 (IL-8) was instilled into the round window niche of
      rats through a small perforation in the tympanic membrane in order to study its
      effect on inner ear function by electrophysiological and morphological
      techniques. The frequency-specific auditory brainstem response (ABR) was recorded
      at the frequencies 4, 8, 10, 12, 16 and 20 kHz just before and 1, 2, 5 and 14
      days after instilling IL-8 to ascertain the hearing level during each interval.
      Morphological examination by light microscopy was performed during the same
      interval following the instillation of IL-8. On day 1, the rise in ABR threshold
      was within 5 dB SPL (non-significant elevation). However, a significant threshold
      elevation (above 5 dB SPL) occurred in high-frequency areas (16 and 20 kHz) on
      day 2, and in middle frequency areas (10 and 12 kHz) on day 5 with sensorineural
      hearing loss type intensity-latency curves. By day 14, the elevated thresholds
      had returned to pre-instillation levels. In the lowest areas (4 and 8 kHz), no
      significant threshold elevation was detected at any time during the observation
      period. By light microscopy, on day 1, clusters of inflammatory cells
      (predominantly neutrophils) were observed just outside the round window membrane
      (RWM), while only a few neutrophils were detected in the cochlea. These cells
      were still present outside the RWM on day 2. The neutrophils had disappeared by
      day 5 and only macrophages were present on the middle ear side of the RWM.
      However, throughout the observation period, the organ of Corti and stria
      vascularis appeared to be intact. These results suggest that IL-8 in the middle
      ear cavity is able to influence inner ear function.

PMID- 9646305
TI  - Stereocilia-like structures in the endolymphatic sac in Meniere's disease and
      acoustic neuroma.
AB  - The vestibular aqueduct was surgically removed in 3 patients undergoing
      labyrinthectomy due to severe Meniere's disease (MD). Stereocilia-like structures
      were found in the luminal contents of the endolymphatic sac (ES) in all of these
      patients. The ES from 18 patients with acoustic neuroma were used as controls. In
      1 of these, numerous stereocilia-like structures were found in the ES and in 3
      additional patients, a few isolated cilia-like structures were disclosed. The
      findings may suggest an ongoing hair cell degeneration in the inner ear that is
      more advanced in patients with MD. The data also suggest that the endolymphatic
      duct is patent and that a longitudinal flow of endolymph also occurs in patients
      with MD.

PMID- 9646306
TI  - Long-term fate of Plastipore in the middle ear.
AB  - Four Plastipore prostheses, removed at revision surgery 7-10 years after
      implantation, have been examined. The gross appearance of the prostheses was
      preserved. The prostheses were surrounded by a fibrous tissue capsule and showed
      fibrous tissue ingrowth localized in peripheral zones. Foreign-body giant cells
      and macrophages were detected in small numbers. Histologic evidence of breakdown
      of the prostheses, in the form of microdisintegration of the walls of micropores,
      was detected on a small scale. Compared to the massive foreign-body reactions
      reported in short-term studies, the tissue reaction apparently subsides with time
      and becomes insignificant. Strict criteria for insertion should be regarded.

PMID- 9646307
TI  - Ciliary beat frequency, olfaction and endoscopic sinus surgery.
AB  - We assessed prospectively changes in olfaction and ciliary beat frequency (CBF)
      after functional endoscopic sinus surgery (FESS) in 70 patients with chronic
      sinusitis. CBF was measured by the microscopic-photometry technique 2, 4 and 6
      months after FESS. Olfaction was evaluated by the Erlangener Smell Identification
      Test. Preoperative CBF was markedly reduced due to the infectious process. CBF
      was significantly improved (p < 0.001), reaching normal values 6 months
      postoperatively despite the endoscopic examination revealing normal nasal mucosa
      at around 3 months. The pattern of improvement of CBF was linear being more rapid
      between months 4 and 6. After operation olfactory-impaired patients were improved
      subjectively and objectively (p < 0.001 and p = 0.003). We conclude that impaired
      olfactory ability and CBF are significantly improved after FESS, and FESS demands
      longer postoperative follow-up periods for at least 6 months even if the clinical
      evaluations were normal.

PMID- 9646308
TI  - Correlation between objective and subjective assessments of nasal patency.
AB  - The correlation between the subjective sensation of nasal patency and nasal
      resistance (NR) to airflow was examined in a large population. The subjective
      estimation was assessed by a visual analogue scale and the NR by active anterior
      rhinomanometry in 158 subjects. Evaluation and statistical analysis--including
      correlation and regression analysis--were computerized. A statistically
      significant correlation was found between the subjective and objective values (r
      = -0.301, p < 0.001). There was no correlation between the parameters if the
      groups with or without nasal obstruction were evaluated apart. In 84% of the
      cases, the narrower side of the nose was identified with both the objective and
      the subjective methods. Statistically significant correlations were exhibited
      between the subjective and the objective measures if unilateral NR and the
      ipsilateral subjective values were related to each other (n = 316, r = -0.476, p
      < 0.001), in both cases, on the side of the higher and the lower NR. The best
      correlation was found on the side of the higher NR, that is when nasal breathing
      is more impeded. Subjective estimation seems to be sufficient only to indicate
      the more obstructed side of the nose independently from the dimensions of the NR
      values.

PMID- 9646309
TI  - Results after resection of intraoral cancer and reconstruction with the free
      radial forearm flap.
AB  - Between 1989 and 1996, 47 patients with an intraoral squamous cell carcinoma
      underwent tumor resection and reconstruction with a free volar forearm flap.
      Tumor resection and neck dissection were performed by a head and neck surgeon and
      the free tissue transfer by a plastic surgeon. Preoperative radiation therapy was
      given to 44 of 47 patients and postoperative radiation therapy to 2. One other
      patient was not irradiated. There were 15 females and 32 males, with a mean age
      of 61 years. The primary site of the cancer was the tongue in 15 cases, the floor
      of the mouth in 15, the tonsil in 10, the bucca in 3 and the retromolar trigone
      in 4 cases. The flap was harvested from the left forearm in 34 and from the right
      in 13 patients. The mean operation time was 10 h (range 6-20) and the mean
      intraoperative bleeding was 486 ml (250-2,500). Forty-four of 46 flaps healed
      completely. Twelve revisions on 9 free flaps were performed between 6 h and 6
      days postoperatively. Overall revisional surgery was done in 9 of 47 cases (19%).
      Two flaps could not be saved (4%). Infections/fistulas in the neck occurred in 11
      of 46 cases (24%). Complete healing of the donor site occurred at a mean of 2.5
      months (1-5). Nine patients developed complications at the donor site, 3
      hematomas and 6 superficial infections (19%). Twenty-seven of 47 patients are
      still alive (57%). The mean survival time was 49 months (16-71).

PMID- 9646310
TI  - Platysma myocutaneous flap including the external jugular vein with special
      reference to neck dissection.
AB  - Although platysma myocutaneous flap (PTMCF) is suitable for a small intraoral
      defect, combination with neck dissection (ND) decreases the viability. Therefore,
      a version of PTMCF was devised to increase the viability. This version consists
      of three points: preservation of the external jugular vein (EJV), preservation of
      the facial artery after skeletonization from the submandibular gland, and a new
      incision around the flap. This procedure was applied to 21 patients with
      intraoral cancer. All 21 patients underwent some kind of ND. The average viable
      area of transferred skin was 80%. This rate was significantly better than that
      for 46 previous cases using Farr's modification with ND, in which the facial
      artery was divided. Viability of the flaps was analyzed by the vessels preserved,
      especially by EJV. ND is not a contraindication with this version.

PMID- 9646311
TI  - Late-onset sensorineural hearing loss in Coffin-Lowry syndrome.
AB  - The Coffin-Lowry syndrome (CLS) is a rare clinical entity where patients present
      with a characteristic facies, mental retardation and bone abnormalities. So far
      about 60 cases have been reported. Sensorineural hearing loss is not a
      characteristic symptom and a late-onset hearing loss has not been reported so
      far. We report on 4 brothers with CLS, aged 9-17 years, of whom 3 suffered from a
      severe sensorineural hearing loss with an onset during late childhood and
      adolescence after a normal hearing during early childhood. CT scans revealed no
      cochlear abnormalities. The boys were successfully equipped with hearing aids. It
      is suggested that in all CLS patients the hearing ability should be examined
      during early infancy and retested regularly in cases with normal hearing as these
      cases indicate that in CLS a late-onset hearing loss is possible during late
      childhood and adolescence.

PMID- 9646312
TI  - Bilateral facial nerve palsy: four case reports.
AB  - Bilateral facial nerve palsy is relatively uncommon and may occur in association
      with a variety of neurological, infectious, neoplastic or degenerative disorders.
      Presentation is made of 4 cases of bilateral facial diplegia due to a refractory
      anemia with excess of blasts, a Lyme disease and a tuberculoid leprosy. In one of
      these patients the cause of bilateral seventh-nerve palsy was unknown (Bell's
      palsy). Facial palsy returned to normal after treatment with steroids in 3
      patients. The patient with myelodysplastic syndrome did not show any improvement
      and died 6 months after diagnosis.

PMID- 9646313
TI  - Management of chylous fistula using the fibrin adhesive set.
AB  - Chylous fistula complicates 1.1% of all radical neck dissections, and 2.4% of
      left-sided dissections. The standard treatment of established chylous leak in the
      reported cases is a pressure dressing applied to the lower neck. Here we present
      a case of chylous fistula, where conservative methods failed to cope with this
      complication. The additional application of a fibrin adhesive set was a
      successful modality of treatment.

PMID- 9646314
TI  - Successful treatment of angioimmunoblastic lymphadenopathy with dysproteinemia by
      local irradiation.
AB  - We report an 85-year-old man presenting with angioimmunoblastic lymphadenopathy
      with dysproteinemia (AILD) of the palatine tonsil with cervical and axillary
      lymph node enlargement, pleural effusion and hypergammaglobulinemia. The patient
      was treated in Internal Medicine with combined chemotherapy with steroids which
      resulted in a complete remission. However, he returned almost 1 year later with
      an ulcerative lesion in the left palatine tonsil, with no lymph node involvement.
      Considering that the patient was an elderly person, chemotherapy had been
      administered during the initial admission, tumor cells appeared to originate from
      T cells and relapse occurred only in the local lesion, the lesion was treated by
      local irradiation using 60Co at a dose of 40 Gy, which produced a complete
      resolution. Radiotherapy appeared to be effective for the treatment of localized
      lesions of AILD.

PMID- 9646316
TI  - [Bone metastases. 2].

PMID- 9646315
TI  - Lupus pernio with involvement of nasal cavity and maxillary sinus.
AB  - Histological demonstration of sarcoidosis affecting the paranasal sinus is rare
      in the clinical practice. In this paper, we present a case with a diagnosis of
      lupus pernio with extensive involvement of the nasal cavity and the right
      maxillary sinus. Long before being diagnosed as having lupus pernio, the patient
      had had a long history of nasal obstruction and had been treated surgically
      without success on 3 occasions. The literature on the topic is reviewed.

PMID- 9646317
TI  - [Interventional therapy of primary and secondary tumors of the spine].
AB  - Therapeutic interventions in the skeletal system are an essential part of
      interventional radiology. Although in terms of figures these procedures are
      applied less frequently, they are very effective. Percutaneous transarterial
      embolization of a spinal tumor is well-established interventional treatment. It
      is primary treatment for preoperative devascularization, but also for palliation
      of pain and for reduction of tumor volume. As an alternative access for
      embolization, direct percutaneous puncture of a vertebra is used. A new and
      promising technique is vertebroplasty, the percutaneous injection of acrylic
      surgical cement in destroyed vertebrae. The present paper discusses indications,
      technique, results and complications of these interventional therapeutic
      modalities in the treatment of primary and secondary spinal tumors.

PMID- 9646318
TI  - [Surgical management of skeletal metastases of the extremities].
AB  - Operations on skeletal metastases of the extremities represent the most frequent
      surgical treatment in orthopedic oncology. From 1970 to 1997, 340 patients were
      operated on in 383 surgical procedures in the Orthopedic Department of the
      University of Heidelberg. Carcinoma of the breast and renal cell carcinoma were
      the most common primary tumors. Operations concerned mainly the femur with
      acetabulum (55%) and the humerus with glenoid (25%). A pathologic fracture
      occurred in 51%. While in these cases surgical treatment is absolutely necessary,
      it is contraindicated in preterminal patients. In imminent fractures or
      peripheral compression syndromes, the indication is relative and has to be
      justified on a multidisciplinary basis. Marginal resection of the tumor is
      allowed because of the limited life expectancy of most patients. Only in patients
      with solitary metastases and a better prognosis the resection of metastasis
      margin can be more extensive. Intensification of local therapy by adjuvant
      irradiation is indicated in an R2 situation, depending on the patient's
      prognosis. An analysis of our cases from 1994 to 1996 exemplifies the increasing
      use of modular tumor endoprostheses (52%). In meta-diaphyseal and diaphyseal
      cases, cement-augmented osteosynthesis is mainly used (34%). The application of
      these established reconstruction techniques after metastasis resection in cases
      with adjuvant radiotherapy assures a pain-free extremity capable of weight
      bearing.

PMID- 9646319
TI  - [Surgical therapy of spinal metastases].
AB  - Bone metastases of the vertebral spine occur frequently after breast cancer,
      hypernephroma or thyroid carcinoma. Located commonly in the lumbar and thoracic
      spine, half of the lesions are found in the vertebral body, but in many cases
      lamina and pedicles are also involved. Pain resistant to conservative treatment,
      vertebral compression fracture and segmental instability, together with
      progredient neurologic deficits and para- or tetraplegia, all make operative
      intervention mandatory. In this article dorsal decompression and stabilization
      are compared to ventral decompression and compound osteosynthesis. Segmental
      stability and life-time prognosis of the patient are important factors to decide
      on the best surgical procedure. Dorsal decompression without stabilization should
      only be performed as a palliative procedure in patients with an inoperative
      tumor, poor prognosis, or if the estimated postoperative segmental stability
      seems to be sufficient. In cases of a solitary metastasis, after radical
      resection of the primary tumor and when the prognosis is good total vertebrectomy
      can be performed. In addition to surgical treatment, adjuvant chemotherapy and/or
      radiation therapy should be performed in a multidisciplinary setting.

PMID- 9646320
TI  - [Surgical management of pelvic metastases].
AB  - Due to a rise in life expectancy as well as improved adjuvant and diagnostic
      measures the incidence of clinically symptomatic metastases has significantly
      increased. In terms of indication and operative technique in the treatment of
      these lesions the biologic age, general condition, diagnosis, stage and activity
      of the disease and the patient's prognosis are highly important. Different
      techniques of joint replacement have been described to treat patients suffering
      from metastatic disease of the periacetabular region, being resistant to any kind
      of adjuvant therapy. From 1977-1996 21 patients with a periacetabular lesion
      received a tumor prosthesis following internal hemipelvectomy (average age 60
      years; average survival 23.1 months). Perioperative complication rate was 42%,
      functional results were good (n =), fair (n = 9) and poor (n = 2). Mobilisation
      and analgesia are the most important therapeutic goals. The quality of the
      patient's life postop is the major point.

PMID- 9646321
TI  - [Prognosis of skeletal metastases].
AB  - Surgical resection of osseous metastases is becoming more and more important in
      obtaining longer overall survival in carcinoma patients. In 228 cases surgically
      treated at our institution between 1980 and 1993, the survival was 49% after 1
      year, 32% after 2 years, 22% after 3 years and, finally, 11% after 5 years.
      Retrospectively evaluated, breast and thyroid carcinoma proved to be of positive
      prognostic influence and lung cancer of negative significance. As a main
      significant parameter, further extraosseous metastases were evaluated. The
      prognostic influence of the number of osseous lesions could only be demonstrated
      in breast and renal cell carcinoma without involvement of further organs. Age and
      location of the skeletal lesions proved to be of no prognostic influence. Based
      on these prognostic parameters, three subgroups of patients with worse, median
      and good long-term survival could be defined. In conclusion, the indication and
      amount of surgery can be based on these prognostic factors, leading to a decrease
      in morbidity and hospitalization time in patients with limited survival.

PMID- 9646322
TI  - [Biometric planning of clinical-orthopedic studies. The optimal test].
AB  - A determinant for the evidence of a clinical trial is the magnitude of the sample
      size. The proper sample size can be easily computed with the knowledge of alpha,
      power and effect size. Standard values for alpha and power in clinical trials are
      5% and 90%, respectively. As a consequence, effect size is crucial for the sample
      size. The effect size has to be determined by the clinician according to medical
      considerations. Possible consequences of sample sizes that are either too small
      or too large are discussed with regard to the meaning of alpha, Power and effect
      size. Trials with improper small sample sizes have a high risk of false negative
      results, and may subsequently prevent the application of a possibly effective
      therapy. Trials with improper large sample sizes may result in statistically
      significant differences without any clinical relevance.

PMID- 9646323
TI  - [Remembering Prof. M. H. Retting].

PMID- 9646324
TI  - [Cartilage regeneration and substitution].

PMID- 9646325
TI  - Developmental expression of cytochrome P450 enzymes in human liver.
AB  - Drug-metabolizing cytochrome P450 enzymes, the major phase I enzymes, are active
      in human liver already at very early stages of intrauterine development, although
      presumably at fairly low concentrations and in low numbers. During maturation,
      these enzymes go through various developmental programmes towards adulthood. The
      major increase both in abundance as well as in number of different enzymes takes
      place after birth, probably during the first year of life. Detailed information
      concerning these developmental changes is still limited. The major drug
      metabolizing P450 enzymes appear to be primarily members of the CYP3A subfamily
      in all stages of development. The balance between different members of this
      subfamily, however, undergoes significant switches from the foetal predominant
      CYP3A7 to the major adult form CYP3A4. The ontogeny of the other cytochrome P450
      enzymes is less well characterized, but the major switch-on appears to occur
      mainly after birth. Developmental expression of P450 enzymes is one of the key
      factors determining the pharmacokinetic status of developing individuals both pre
      and postnatally.

PMID- 9646326
TI  - Effect of chronic administration of magnesium sulfate on 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine-induced neurotoxicity in mice.
AB  - This investigation was aimed to study the effect of magnesium on 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in mice. Four
      groups of mice were given magnesium sulfate (MgSO4.7H2O) in drinking water at
      four different concentrations of 0.0 g/l (control), 2.5 g/l (low), 5.0 g/l
      (medium) and 10.0 g/l (high) respectively for a period of 16 weeks; these animals
      also received MPTP (30 mg/kg, intraperitoneally daily) during the last five days
      of Mg treatment. Other four groups of mice were given similar dose regimen of
      MgSO4 but received injections of saline instead of MPTP. Seventy-two hr after the
      last dose of MPTP, neurobehavioural studies including locomotor activity, pole
      climbing test and heart nociception test were performed and striata were
      collected for the analysis of dopamine. The results of this study show that
      treatment of mice with MgSO4 or MPTP individually has no effect on their
      behaviour. Concomitant administration of low dose of MgSO4 (2.5 g/l) along with
      MPTP produced increase in motor activity and latency to heat stimuli; whereas
      medium and high doses of MgSO4 in combination with MPTP produced opposite (as
      compared to low dose) effects resulting in a decrease in motor activity and
      latency to heat stimuli and increase in pole climbing time. However, MgSO4 dose
      dependently exacerbated MPTP-induced depletion of striatal dopamine. The
      mortality was drastically increased (30-55%) in the animals receiving combined
      treatments of MPTP and MgSO4 as compared to the mice treated with MPTP alone
      (12%). This study clearly points towards the ability of MgSO4 to modify MPTP
      induced neurotoxicity.

PMID- 9646327
TI  - Effect of stem cell factor, interleukin-6, nitric oxide and transforming growth
      factor-beta on the osteoclast differentiation induced by 1 alpha,25-(OH)2D3 in
      primary murine bone marrow cultures.
AB  - Osteotropic hormones and cytokines are involved in the differentiation of
      osteoclast progenitors from haematopoietic stem cells to multinucleated
      osteoclasts which mediate bone resorption. Stem cell factor, interleukin-6,
      nitric oxide, and transforming growth factor-beta are implicated in the
      regulation of bone resorption by osteoclast. We test whether stem cell factor,
      interleukin-6, nitric oxide, and transforming growth factor-beta affect the
      generation of osteoclast-like multi-nucleated cells induced by 1 alpha,25
      (OH)2D3. 1 alpha,25-(OH)2D3 increase the generation of osteoclast-like cells
      retaining osteoclast characteristics including multinuclearity and positive
      staining for tartrate-resistant acid phosphatase. Combined treatment of stem cell
      factor with interleukin-6 synergistically potentiates the ability of 1 alpha,25
      (OH)2D3 to generate tartrate-resistant acid phosphatase-positive multinucleated
      cells. However, either stem cell factor or interleukin-6 alone does not induce
      the generation of tartrate-resistant acid phosphatase-positive multinucleated
      cells. Transforming growth factor-beta produces a biphasic effect on osteoclast
      generation induced by 1 alpha,25-(OH)2D3. Transforming growth factor-beta
      stimulates osteoclast generation at low concentration (0.1 ng/ml) whereas it
      suppresses the formation of osteoclast-like cell at higher concentration (1
      ng/ml). Sodium nitroprusside, a donor of nitric oxide, almost completely inhibits
      the generation of 1 alpha,25-(OH)2D3-induced osteoclast at high concentration
      (100 microM), but it significantly enhances the osteoclast generation at low
      concentrations (3 microM). These results suggest that stem cell factor,
      interleukin-6, transforming growth factor-beta, and nitric oxide interact with 1
      alpha,25-(OH)2D3 to modulate the differentiation of hematopoietic precursors
      toward committed osteoclast precursors.

PMID- 9646328
TI  - Cadmium uptake from apical membrane of LLC-PK1 cells via inorganic anion
      exchanger.
AB  - Effects of Na+, Cl-, OH- and HCO3-, and an inorganic anion exchange inhibitor
      (HCO3-/Cl-), 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, on Cd uptake from
      the apical membrane of LLC-PK1 cells were investigated to elucidate the mechanism
      of Cd uptake by these cells. Furthermore, the initial uptake of Cd incubated at
      different temperatures was analyzed by using the Arrhenius plot to test if Cd is
      taken up by the cells via the carrier-mediated process. The cells were incubated
      with 1 microM CdCl2 for 30 min. at 37 degrees in phosphate buffer containing NaCl
      at pH 5.5 or 7.4. Cd accumulation by the cells at pH 7.4 was about 5 times higher
      than at pH 5.5. Replacement of NaCl in the phosphate buffer with KCl or mannitol
      decreased the Cd accumulation at pH 7.4 about 80%, but had no effect at pH 5.5.
      The addition of 2 mM NaHCO3 to the pH 7.4 buffer containing NaCl significantly
      increased the Cd accumulation, and pretreatment of the cells with the inorganic
      anion exchange inhibitor abolished this effect of NaHCO3 on Cd accumulation. The
      cells were incubated for 10 min. at different temperatures with 1 microM CdCl2 in
      the phosphate buffer containing NaCl at pH 7.4 in the presence or absence of 2 mM
      NaHCO3 or at pH 5.5 in the absence of NaHCO3. In all cases, the Arrhenius plots
      of Cd accumulation were nonlinear. The breakpoint was observed at about 30
      degrees in the Cd accumulation at pH 7.4 in the presence of NaHCO3, suggesting
      the involvement of a carrier-mediated process. This breakpoint was not as clear
      in the Cd accumulation at pH 7.4 in the absence of NaHCO3 and not observed at all
      at pH 5.5. These findings suggested that Cd is partially taken up from the apical
      membrane of LLC-PK1 cells via the inorganic anion exchanger and the uptake of Cd
      is more efficient at alkaline pH and in the presence of Na+, Cl- and HCO3-.

PMID- 9646329
TI  - Effect of t-butylhydroperoxide on chloride secretion in rat tracheal epithelia.
AB  - Oxidative stress has been known to play important roles in various inflammatory
      diseases of lung such as allergic bronchitis, dust particle-induced inflammatory
      diseases, or chronic bronchitis. However, the effects of oxidants on Cl-
      secretion in tracheal epithelia have not been determined. To examine the effects
      of oxidants on Cl- secretion of the airway epithelia rat tracheal epithelial
      cells were cultured on porous filters and short circuit current (Isc) was
      measured in an Ussing chamber system. t-Butylhydroperoxide, which was widely used
      as a model substance to study the mechanism of cell injury resulted from
      oxidative stress, induced a transient increase in Isc by dose-dependent manner.
      The response was not observed in Cl(-)-free medium, and inhibited by 100 microM
      bumetanide. N(-Diphenyl-1,4-phenylene-diamine (DPPD, 5 microM), an inhibitor of
      lipid peroxidation, blocked the t-butylhydroperoxide response. When t
      butylhydroperoxide was added after the administration of forskolin or H-89, a
      protein kinase A inhibitor, the t-butylhydroperoxide-induce Isc increase was
      abolished. Pretreatment of indomethacin (10 microM) completely inhibited the t
      butylhydroperoxide response, but pretreatment of thapsigargin (1 microM) did not,
      t-Butylhydroperoxide induced gradual increases in cytosolic Ca2+ level, and
      increased [3H]arachidonic acid release in the presence of thapsigargin. These
      results indicate that t-butylhydroperoxide stimulates Cl-secretion via activation
      of phospholipase A2 and subsequent production of cyclooxygenase metabolities by
      Ca(2+)-dependent and -independent mechanisms.

PMID- 9646330
TI  - Short-term effects of nicotine on bone and calciotropic hormones in adult female
      rats.
AB  - This study assessed the effects of two months nicotine treatment on bone
      formation and resorption end-points in adult, female rats. In addition, the
      concentrations of calciotropic hormones which included parathyroid hormone,
      calcitonin, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in rats (7 months
      old) were determined. All animals received either saline (n = 7/group), nicotine
      (3.0 mg/kg/day) (n = 7/group) or nicotine (4.5 mg/kg/day) (n = 7/group) via
      subcutaneous implantation of osmotic minipumps containing either saline or
      nicotine for a period of two months. Serum, right tibia, left femur and lumbar
      vertebra (3-5) were collected for determination of hormonal concentrations as
      well as various parameters, including histomorphometry, bone mineral density,
      bone mineral content and vertebral strength. Although nicotine-treated rats
      showed a lower level of 25-hydroxyvitamin D [54.4 +/- 3.1 ng/ml for the 3.0
      mg/kg/day and 55.8 +/- 2.8 for the 4.5 mg/kg/day group] (mean +/- S.E.M.) as
      compared to controls (74.8 +/- 2.8 ng/ml) (P < 0.01, Newman-Keuls test), no
      significant difference could be detected for the levels of the remaining
      hormones. Similarly, no statistical differences were detected on
      histomorphometric end-points, bone mineral density, bone mineral content and
      vertebral strength of rats. We conclude that, in spite of lowering serum 25
      hydroxyvitamin D by about 30%, nicotine administration of two months duration
      does not alter bone mass, strength or formation and resorption end-points.

PMID- 9646331
TI  - Amlodipine dynamic effects and myocardial pharmacokinetics in the isolated and
      perfused guinea-pig heart.
AB  - Myocardial dynamic effects and pharmacokinetics of amlodipine were studied in the
      isolated retrogradely perfused and spontaneously beating guinea-pig heart.
      Pharmacokinetic analysis of drug accumulation showed one-compartment
      characteristics with an half-life of 76 min. Whereas disposition exhibited two
      compartment characteristics with phasic half-lives of 25 and 174 min.,
      respectively. Myocardial drug accumulation was increased by 600 times at steady
      state compared to the perfusion liquid. Dynamic effect parameters were studied
      during increasing amlodipine concentrations from 0.16 to 220 nM. Dynamic steady
      states developed within 20 min. Coronary flow-rate increased with an Emax of 119%
      and an EC50 of 1.2 x 10(-8) M. Amlodipine produced inhibitory effects on
      contraction amplitude and velocities of contraction and relaxation. Observed Emax
      values and curve-fitted EC50-values were: 97, 97 and 94% and 1.10(-8), 7.7 x 10(
      9) and 2.1 x 10(-8) M, respectively. Heart frequency was not changed. Oxygen
      consumption increased markedly to a maximum of 44% at 3 x 10(-8) M amlodipine and
      then decreased to nearly initial values. The frequency-corrected QT-interval
      decreased to a maximal extent of 20% at the three highest concentrations.
      Myocardial efficiency expressed as the ratio of contraction velocity times
      frequency to oxygen consumption exhibited a progressive decline to about 2% of
      initial values. The PQ-interval was not changed and the QRS-interval showed only
      a small but significant decrease at the highest amlodipine concentration. No
      arrythmogenic effects were observed. The study demonstrated a very slow
      accumulation and disposition of amlodipine in the guinea-pig heart with a steady
      state myocardial drug concentrating accumulation of 600 times. Marked increase in
      coronary flow-rate and oxygen consumption accompanied by a progressive negative
      inotropic effect were observed.

PMID- 9646332
TI  - The influence of selected herd factors and a badger-intervention tuberculosis
      control programme on the risk of a herd-level trade restriction to a bovine
      population in Ireland.
AB  - The risk of a trade restriction to cattle herds between 1990-1994, as a result of
      failing the tuberculin skin test or disclosure of visible lesions in the
      abattoir, was compared in two areas in East Offaly, Ireland. Cattle herds from
      the Project area where badgers were systematically removed over a 7-year period
      (1989-1995) were compared to herds from a Control area where no wildlife
      intervention programme had taken place. A Cox proportional hazard model
      indicated, for example, that the risk of a herd-level trade restriction to herds
      with 30 animals in the Control area was 1.4 times the risk to similar-sized herds
      in the Project area. The study provides evidence that a badger-control programme
      is effective in reducing the risk of a trade restriction to cattle herds as the
      badger represents an important reservoir of Mycobacterium bovis infection for
      cattle.

PMID- 9646333
TI  - Evaluation of an enrofloxacin-treatment program against Mycoplasma gallisepticum
      infection in broilers.
AB  - Three chicken broiler breeder flocks, 7 months of age, were confirmed to have
      Mycoplasma gallisepticum (MG) infection, based on culture of tracheal swabs. A
      total of fifty-five 7-day-old embryos from the three MG-positive flocks had an
      average 27.4% prevalence of MG-infection in their vitelline membrane. Sixty
      randomly selected MG isolates (30 from individual tracheas of breeders and
      another 30 from individual vitelline membrane of embryos) were highly sensitive
      in vitro to enrofloxacin (100%). Three broiler flocks (averaging 15,000 birds per
      flock) from the same three MG-infected chicken boiler breeders were divided into
      halves. The first halves were subjected to an enrofloxacin-treatment program and
      the other halves were controls. Sera collected at different ages of the broiler
      flocks were tested by the enzyme-linked immunosorbent assay for antibodies to MG.
      The absence of MG titers at 45 days of age in birds subjected to the enrofloxacin
      preventive program was compared to an average prevalence of 15.9% in the controls
      (p < 0.05). The lack of MG titers in 45-day-old birds subjected to the
      enrofloxacin-treatment program was associated with lower better feed-conversion
      ratios (p < 0.05).

PMID- 9646334
TI  - Effect of different East Coast fever control strategies on disease incidence in
      traditionally managed Sanga cattle in Central Province of Zambia.
AB  - A clinical trial, including five East Coast fever (ECF) control strategies
      (involving tick control and/or immunisation by infection-and-treatment) in five
      different groups of traditionally managed Sanga cattle, was conducted in Central
      Province of Zambia over 2.5 years between 1992 and 1995. Two groups were kept
      under intensive tick control by weekly acaricide treatment by hand spray; (one
      immunised and one non-immunised), two groups were under no tick control (one
      immunised and one non-immunised), and a fifth, immunised group was maintained
      under strategic tick control (18 sprays yr-1). ECF-specific mortality was highest
      in the non-immunised and non-treated group, while no difference in ECF-specific
      mortality could be observed between animals treated for ECF by immunisation or by
      tick control. Acaricide treatment and/or immunisation reduced the risk of
      clinical ECF by 92%. The results of an artificial challenge experiment at the end
      of the field trial indicated that about 60% of the animals in the control group
      had become infected with Theileria parva without showing clinical signs. ECF
      incidence in non-vaccinated cattle markedly declined six months after
      immunisation--suggesting that the carrier state induced by immunisation did not
      lead to a persistent high incidence, and might accelerate the progress to
      endemicity.

PMID- 9646335
TI  - A case-control study of acute ibuprofen toxicity in dogs.
AB  - A case-control study used data in the National Animal Poison Control Center
      database to characterize risk factors for gastrointestinal ulceration and acute
      renal failure subsequent to the acute ingestion of ibuprofen in the dog. For
      gastrointestinal ulceration (GIU) subsequent to ibuprofen ingestion, four factors
      differentiated the 116 cases from the 93 controls. Risk of GIU was lower for dogs
      where the time from ingestion to intervention was known as opposed to missing
      (adjusted odds ratio (aOR) = 0.12, p = 0.0001). Risk of GIU was also lower for
      the Labrador breed (aOR = 0.22, p = 0.004). Risk of GIU was higher for each unit
      of the logarithm of time to intervention (aOR = 2.63, p = 0.0002) and for the
      German Shepherd breed (aOR = 5.67, p = 0.14). For acute renal failure (ARF)
      subsequent to ibuprofen ingestion, two factors differentiated the 80 cases from
      the 64 controls. Risk of ARF was lower for dogs where the time from ingestion to
      intervention was known as opposed to missing (aOR = 0.15, p = 0.0001). Risk of
      ARF was higher for each unit of the logarithm of time to intervention (aOR =
      2.16, p = 0.01). Although this study failed to describe a dose-response
      relationship, it appears that there are significant breed differences in
      susceptibility to GIU subsequent to ibuprofen exposure. Time to intervention was
      critical for both GIU and ARF outcomes. Dogs, particularly German Shepherds,
      ingesting even small amounts of ibuprofen, may need to be managed aggressively.

PMID- 9646336
TI  - Observations on ethnoveterinary medicines in Trinidad and Tobago.
AB  - In 1995 research was conducted in Trinidad and Tobago with the aim of collecting
      knowledge on ethnoveterinary medicines in order to lay a foundation for further
      scientific study and validation. This paper describes only the ethnoveterinary
      practices used in the poultry sub-sector. A four stage process was used to
      conduct the research and document these ethnoveterinary practices. 28
      ethnoveterinary respondents were identified using a modified Rapid Rural
      Appraisal (RRA) technique, the student essay method. Semi-structured interviews
      were conducted with these respondents as well as with 30 veterinarians, 27
      extension officers and 19 animal health assistants/agricultural officers, and the
      7 key respondents that they identified. 5 participatory workshops were then held
      with 55 of the respondents interviewed to discuss the data generated from the
      interviews and to determine dosages for some of the plants mentioned. 12 plant
      species were used to treat 4 categories of health problems common to poultry
      production. Aloe vera, Bryophyllum pinnatum, Citrus sp. and Momordica charantia
      were the main medicinal plants being used.

PMID- 9646337
TI  - An outbreak of East Coast fever in a herd of Sanga cattle in Lutale, Central
      Province of Zambia.
AB  - An outbreak of East Coast fever (ECF) occurred in an experimental herd of Sanga
      cattle maintained under a traditional rangeland grazing system at Lutale, Central
      Province of Zambia. Two groups of cattle had been kept under different tick
      control regimens for several years prior to the introduction of the disease and
      epidemiological information on the outbreak were recorded. Weekly tick control
      was no sufficient to achieve full protection against Theileria parva infection.
      Systematic body temperature monitoring seems to be a good method for early
      detection of infection resulting in an important reduction of the case fatality
      rate after treatment with anti-theilerial drugs.

PMID- 9646338
TI  - [Graduate and Continuing Education Committee of the German Society of Radiology].

PMID- 9646339
TI  - [Evaluating tumor vascularization with Doppler ultrasound].
AB  - Tumor vessels are structurally and functionally abnormal. The degree of
      vascularity determines a tumor's aggressiveness, as well as its radiosensitivity
      and chemosensitivity. Assessing tumor vascularity may help in differential
      diagnosis and assist therapy monitoring. Together with other imaging methods,
      Doppler sonography has been evaluated for the assessment of tumor vascularity but
      has proven to be difficult to evaluate. Using quantitative analysis methods,
      Doppler sonography was shown to carry differential diagnostic and prognostic
      information as well as to reflect vascular changes during radiotherapy. Its
      clinical role, however, remains to be determined. With current technology neither
      blood volume flow nor microvessel density can be reliably assessed in a tumor
      using Doppler sonography, because it is insensitive to capillary blood flow.
      Upcoming developments such as harmonic imaging and contrast media that generate
      stimulated acoustic emissions are expected to significantly improve sensitivity.

PMID- 9646340
TI  - [B-mode ultrasound and modern Doppler ultrasound methods in diseases of the
      thyroid gland and parathyroid glands].
AB  - Color-coded duplex sonography is the main innovation in diagnostic ultrasound in
      recent years. It allows quantification of tissue vascularity and appreciation of
      vascular morphology. Due to the unique thyroid hypervascularity in Graves'
      disease this diagnosis can be made with color Doppler sonography alone. The
      decrease of vascularity during the course of disease is a relevant parameter
      throughout the follow-up. Hypervascularity is also observed within areas of
      inflammatory infiltration in thyroiditis, but the level is lower than in Graves'
      disease. Sonographic differentiation of benign from malignant thyroid nodules is
      not possible yet. Color-coded duplex sonography is not useful in the initial
      detection of parathyroid masses, but may be helpful in distinguishing parathyroid
      lesions from other cervical masses.

PMID- 9646341
TI  - [A multicenter study of diagnostic criteria in ultrasound mammography.
      Statistical pitfalls and ways out of the data jungle].
AB  - This paper demonstrates the statistical processing of data from a multicentric
      study. Seventy-seven patients with a suspicious, solid breast mass were included
      in a two-center study, using clinical breast examination, mammography, and
      ultrasound. The assessment was formalized using a uniform evaluation sheet. The
      prospective results of the examinations were compared with the histologic report.
      The degree of interdependence between an examiner's diagnosis and diagnostic
      criteria used was assessed using the kappa statistics. We found that despite
      standardized assessment, the criteria used for differential diagnosis were at
      least partially different. The criteria valid for diagnosis at both centers were
      whether a mass fitted well into the surrounding tissue or led to destruction or
      architectural distortion, whether it was fixed to the surrounding tissues, as
      assessed by sonopalpation maneuvers, and whether it borders were sharp or
      unsharp.

PMID- 9646342
TI  - [Diagnosis of pulmonary diseases with transthoracic ultrasound].
AB  - The indications or ultrasound in the evaluation of pulmonary disorders are
      described. Clinical applications are several lung diseases in adults and
      especially in children. In specific, well-defined applications, the feasibilities
      of ultrasound are promising. Sonography provides important additional information
      to chest X-ray and is even superior to CT under special circumstances. Pulmonary
      sonography is a useful link between conventional X-ray and more expensive cross
      sectional imaging. In the evaluation of pulmonary diseases at present the
      potential of ultrasound is not optimally used.

PMID- 9646343
TI  - [After-care of TIPSS patients. Comparison between color Doppler ultrasound and
      portography].
AB  - PURPOSE: Comparison of color Doppler sonography and venous portography in
      patients with a transjugular intrahepatic portosystemic stent shunt (TIPSS).
      MATERIALS AND METHODS: In a prospective study 40 consecutive patients with TIPSS
      underwent venous portography and color Doppler sonography on the same day as
      follow-up. Shunt velocities were recorded within the TIPSS at the proximal
      (hepatic vein segment) and distal part (portal vein segment). RESULTS: In 28
      patients with functioning TIPSS the mean shunt velocity ranged between 30 and 120
      cm/s (median 60 cm/s) at the portal vein segment and between 60 and 155 cm/s
      (median 82 cm/s) at the hepatic vein segment. There was a significant increase of
      the mean shunt velocity in the hepatic vein segment (P < 0.001). In 12 patients
      with compromised TIPSS the mean shunt velocity was reduced to 26 +/- 7 cm/s at
      the portal venous end (P < 0.0001). CONCLUSION: Because of an accelerated shunt
      velocity in the hepatic vein segment a site-specific evaluation of both TIPSS
      endings is necessary with color Doppler sonography. In compromised TIPSS the
      shunt velocity is reduced at the portal venous end. Color Doppler sonography is a
      valid non-invasive means for follow-up of patients with TIPSS.

PMID- 9646344
TI  - [Ultrasound anatomy and pathology of the elbow joint in the child and in the
      adult].
AB  - The aim of this study was to evaluate the sonographic anatomy of the elbow joint
      in children and adults and to point out the indications for an ultrasound
      examination after elbow joint trauma. The study was carried out using isolated
      joint specimens, muscle specimens and cadaver limbs. Additionally, a clinical
      trial was performed using high-resolution ultrasound probes (7.5-12 MHz). When
      assessing standard sections, one has to consider both the position of the elbow
      joint in the frontal plane and the position of the forearm during pro- and
      supination. The outstanding advantage of this method, especially in children, is
      the possibility of a dynamic examination with evaluation of the articular
      cartilage and with a comparison to the healthy contralateral elbow joint.

PMID- 9646345
TI  - [Dynamic assessment of contrast medium enhancement in Doppler ultrasound imaging.
      Current status].
AB  - Findings in previous investigations have indicated that contrast-enhanced colour
      Doppler can be used to improve the demonstration of characteristic features of
      neovascularization in malignancies. However, the quantification of the increase
      in colour Doppler signals after Levovist in the cited study relied only on
      descriptive criteria defined by the investigator, resulting in a subjective
      scoring system. A computer-assisted method for quantitative analysis of colour
      pixel density is a novel approach for objective assessment of colour Doppler
      signal after contrast media administration. After microbubble contrast medium
      injection in 47 patients, carcinomas and benign lesions behaved differently
      regarding degree, onset and duration of Doppler enhancement. However, the high
      interindividual variability and the temporal variations of the Doppler signal
      still limit the value of these criteria for prospective diagnosis. Rapid image
      acquisition techniques are needed in order to apply the necessary mathematical
      processing before the contrast kinetics can be used for diagnostic purposes.

PMID- 9646346
TI  - [3-dimensional echo-enhanced transcranial Doppler ultrasound diagnosis].
AB  - Echo-enhancing agents improve the signal intensity of transcranial Doppler
      signals, enabling a novel approach of three-dimensional transcranial vascular
      imaging by Doppler ultrasound. The basic principle, system requirements and early
      clinical results with a custom built system are described. Transcranial color
      Doppler imaging was performed through the temporal bone acoustic window. During
      i.v. administration of the transpulmonary stable, galactose-based echo-enhancer
      Levovist (Schering) the video output of the ultrasound scanner was digitized and
      the spatial position of the recorded frames was simultaneously registered using a
      mechanical position sensor. After automatic segmentation of the color
      information, the 3D datasets were reconstructed offline using a Unix-based
      workstation (Silicon Graphics). Visualization was achieved by maximum intensity
      projection or surface visualization techniques. Administration of Levovist
      resulted in good enhancement of the vascular Doppler signal intensity, enabling
      acquisition of a 3D dataset of the complete circle of Willis with an imaging
      window of approximately 3-5 min for one i.v. injection. The vascularity of tumors
      could be recorded as a 3D dataset and further analyzed. The power Doppler
      technique with echoenhancement proved a valuable tool for 3D dataset recording.
      3D datasets clearly facilitated the diagnosis of the vascular anatomy and lesion
      vascularity and provided additional information on localization of feeders,
      vascular displacement and extent of tumor vascularity.

PMID- 9646347
TI  - [Use of the ultrasound contrast medium levovist in after-care of liver transplant
      patients. Improved vascular imaging in color Doppler ultrasound].
AB  - INTRODUCTION: A study was carried out to determine whether an improvement in the
      detection of vascular signals in patients after orthotopic liver transplantation
      can be achieved by the use of ultrasound contrast medium in colour Doppler
      sonography. MATERIAL AND METHODS: In the early postoperative follow-up of liver
      transplant recipients, 31 colour Doppler sonograms were obtained in 21 patients
      before and after intravenous injection of the ultrasound contrast agent Levovist
      (Schering, Berlin). A grading score with four categories was used to evaluate the
      sonograms with special regard to the visibility of colour and flow signals in the
      hepatic artery and also in the portal vein and the hepatic veins. The arterial
      and portal venous signals were evaluated in the hepatic portal and in the left
      and right lobe. RESULTS: With contrast enhancement significantly better arterial
      signals were seen in 20 of 31 sonograms for the hepatic portal, in 22 for the
      right lobe and in 26 for the left lobe. Better portal vein signals were obtained
      in 17 of 31 examinations for the right lobe and in 16 for the left lobe; only
      little improvement was obtained for the main stem of the portal vein. For the
      hepatic veins there was no significant improvement. CONCLUSIONS: Early vascular
      complications after liver transplantation usually occur in the hepatic arteries.
      With the use of contrast-enhanced colour Doppler sonography, better detection of
      arterial and peripheral portal signals can be achieved; peripheral portal vein
      branches can be helpful in finding small arteries.

PMID- 9646348
TI  - [Diagnosis of vesicoureteral reflux with echo-enhanced micturition
      urosonography].
AB  - AIM: To ascertain the diagnostic efficacy of reflux sonography with the
      application of the echo-enhancing agent Levovist in comparison with X-ray voiding
      cystourethrography (VCUG). PATIENTS AND METHODS: Echo-enhanced voiding
      urosonography (VUS) and VCUG were performed successively in one examination
      session in 114 children referred for the investigation of possible vesicoureteral
      reflux (VUR). After sonography of the urinary tract the bladder was filled with
      normal saline and Levovist was administered. Reflux was diagnosed when
      hyperechogenic, floating microbubbles appeared in the ureters or renal pelvises.
      RESULTS: A total of 226 kidney-ureter units were available for analysis. Reflux
      was diagnosed in 80 units. All grades of reflux were represented. In 15 kidney
      ureter units VUR was diagnosed with echo-enhanced VUS but was not seen at VCUG.
      The contrary was true in 3 units. High sensitivity and specificity in comparison
      to the VCUG could be attributed to the echo-enhanced VUS. The long imaging window
      attainable with Levovist makes the documentation of convincing images possible,
      contributing to the high diagnostic efficacy. CONCLUSION: Echo-enhanced VUS is
      comparable to VCUG in the diagnosis of reflux.

PMID- 9646349
TI  - [SieScape panorama imaging in radiologic diagnosis].
AB  - Through high-performance computer processing it has become possible to realize a
      new ultrasound imaging process: SieScape imaging. This method provides extended
      field of view images in real time using successive ultrasound images obtained
      when a standard transducer is scanned over a distance of up to 60 cm without any
      position sensor. SieScape offers new possibilities to view topographical anatomy.
      It is especially advantageous for scanning extended and tubular structures as
      well as large and enlarged organs and big pathologic volumes. Parallel scanning
      sequences allow documentation comparable to that of computed tomography. In
      addition, just as in magnetic resonance, variable imaging planes can be realized.
      The following describes the results obtained with SieScape in a multitude of
      clinical applications, especially in examinations of throat, thoracic and
      abdominal walls, breast, and intraabdominal organs as well as the soft tissues
      and small vessels of the extremities. The experience gathered with SieScape
      imaging--its advantages as well as its potential limitations, such as the
      formation of artefacts--is described.

PMID- 9646350
TI  - [SieScape--a new dimension of ultrasound imaging in pediatric radiology].
AB  - The extended field of view imaging procedure named "SieScape" provides, for the
      first time, a mode of establishing in real time a sonographic picture up to 60 cm
      in length. This allows the display of large organs or tumors as well as large
      areas of the body in a single view, without having to assemble several pictures.
      Furthermore, pathological findings can be shown in full size in their
      surroundings. This method makes it considerably easier to convey sonographic
      results to the therapist who is not present at the investigation and to control a
      finding, for instance a tumor, during therapy.

PMID- 9646351
TI  - [Native tissue harmonic imaging].
AB  - Native Tissue Harmonic Imaging is a new way of ultrasound image processing that
      addresses the difficult-to-image patient. By using a Gaussian shaped transmit
      pulse it is possible to separate from the returning echo the harmonic component
      without overlapping with fundamental reflections. The improved image quality
      leads to higher diagnostic confidence so that the use of further imaging
      modalitites is unnecessary.

PMID- 9646352
TI  - [Equipment-independent ultrasound tissue characterization of testis and
      prostate].
AB  - The result of a B-scan ultrasound examination is strongly dependent on the type
      of the used B-system, the chosen system parameters and the experience and
      critical analysis of the clinical investigator. The estimation of quantitative
      acoustic parameters, independent of the type of the used B-system, is one way to
      overcome the subjective nature and the problems of the interpretation of B-scan
      images. A procedure was developed to determine acoustical tissue specific
      parameters (ultrasound attenuation, relative backscatter coefficient) in terms of
      the ultrasound spectroscopy and to correct the system effects. A requirement for
      the calculation of acoustical parameters is the availability of primary rf echo
      signals without any preprocessing. Up to now measurements of phantom materials
      and in-vivo investigations on human testis and prostate have been carried out.
      The effects of pathological changes in the tissue state on the acoustical
      parameters are demonstrated in some examples.

PMID- 9646353
TI  - [Dissection of the inferior vena cava by Fogarty balloon maneuver. A rare
      complication in venous surgery].
AB  - Laceration of the inferior vena cava is an uncommon complication of vascular
      surgery. This report describes the radiologic features (CT and venography) of a
      patient with iatrogenic dissection and perforation of the vessel as a sequel of a
      Fogarty balloon procedure for deep venous thrombosis.

PMID- 9646354
TI  - [Dose distribution in conventional CT and spiral CT and on the topic of dose
      reduction with spiral CT].
AB  - OBJECTIVE: To compare spiral CT with conventional CT with regard to the dose
      distribution in the irradiated body and to examine when an increase in the table
      feed in spiral CT leads to a dose reduction compared with conventional CT.
      METHODS: In order to show the dose distribution, films were exposed in an acrylic
      phantom. The nominal slice thickness was 5 mm; the slice distance in conventional
      CT was 5 and 10 mm; the table feed in spiral CT was 5 and 10 mm per rotation
      (pitch 1 and 2). The integral doses delivered in spiral CT and conventional CT
      were related to the table feed per rotation or slice distance, respectively, and
      were compared arithmetically with each other. RESULTS: Spiral CT showed reduced
      dose fluctuations in axial direction compared with conventional CT. Only in
      conventional CT with a slice distance of 5 mm did the axial dose distribution
      show relative dose peaks near the rotation axis. The longer the body region to be
      examined is, the less table feed is necessary in spiral CT for a dose reduction.
      From a length of 15 times the slice thickness, a pitch of > 1.1 leads to a
      reduction of the integral dose compared with conventional CT. CONCLUSIONS: The
      continuous table feed in spiral CT results in evenly distributed axial dose
      distributions compared with the discontinuous scanning in conventional CT. The
      spiral technique can give an important contribution to dose reduction in CT.

PMID- 9646355
TI  - [Comment on the contribution by J. Zaers et al. Quality assurance in roentgen
      mammography].

PMID- 9646356
TI  - [Comment on the contributions regarding quality assurance in mammography].

PMID- 9646357
TI  - [Sclerosing lesion of the sphenoid bone. Fibrous dysplasia of the sphenoid bone
      of the sclerosing type].

PMID- 9646358
TI  - [With 2001: no more free physician position. Needs prognosis of the Central
      Institute].

PMID- 9646359
TI  - [Radiology scenario 2000. Need-dependent physician supply, economic aspects and
      graduate education in diagnostic radiology: the quadrature of the circle? 2].

PMID- 9646360
TI  - Gentacoll hampers epithelialisation and neovascularisation in excisional wounds
      in hairless mice.
AB  - Our aim was to analyse the effect of Gentacoll on the rate of epithelialisation
      and neovascularisation in wound healing. Standardised circular full thickness
      dermal wounds 2.25 mm in diameter were created on the dorsum of each ear on 24
      hairless homozygous mice (n = 48). The cartilaginous layer was left intact. The
      wounds were treated in a randomised blinded fashion with bovine collagen implants
      with gentamicin (Gentacoll) (n = 17); bovine collagen implants without gentamicin
      (n = 15); and Silicone film (n = 16). Epithelialisation and neovascularisation
      were measured directly by intravital video-microscopy and computerised planimetry
      immediately after the wounds had been made and every third day until the wounds
      closed. Only five of the wounds treated with Gentacoll (n = 17) epithelialised
      completely; and their mean (SEM) epithelialisation time was 22.8 (1.6) days,
      significantly longer than controls without gentamicin (n = 15) for which the
      corresponding figures were 14.5 (0.6) days. In nine wounds treated with Gentacoll
      the ear cartilage in the wound bed perforated and two wounds developed severe
      inflammation, which was followed by self-mutilation. Neovascularisation was
      incomplete in all of the wounds in the Gentacoll group, whereas it was completed
      by 25.3 (0.7) days in the control group treated with implants without gentamicin.
      In the silicone treated group (n = 16), epithelialisation was completed by 12.7
      (0.7) days and neovascularisation by 25.1 (0.5) days. None of wounds treated with
      collagen or silicone alone showed reactions similar to the Gentacoll-treated
      ears. Gentacoll hampers epithelialisation and neovascularisation, and might
      damage exposed cartilage.

PMID- 9646361
TI  - The effect of Gingko biloba extract (Egb 761) as a free radical scavenger on the
      survival of skin flaps in rats. A comparative study.
AB  - Free radicals may have a role in pedicle flap necrosis. We undertook this study
      to compare the effect of various antioxidants and scavengers of free radicals
      such as vitamin E, vitamin C, deferoxamine, and Gingko biloba extract (Egb 761)
      on McFarlane caudal-based dorsal rat flaps. Fifty rats were divided into five
      groups of 10 animals each. One group served as a control (saline) group. The
      remaining four groups were given vitamin C 340 mg/kg, deferoxamine 150 mg/kg, Egb
      761 100 mg/kg, and vitamin E 20 mg/kg. The necrosed area of flap was
      significantly reduced in the deferoxamine (p < 0.001), Egb 761 (p < 0.001), and
      vitamin C (p < 0.05) groups compared with the control group. Vitamin E had no
      effect on distal flap necrosis (p = 0.20).

PMID- 9646362
TI  - Inhibition of plasma extravasation after burns by D-myo-inositol-1,2,6
      trisphosphate using digital image colour analysis.
AB  - D-myo-inositol-1,2,6-triphosphate (1,2,6-IP3) has beneficial effects in
      experimental, progressive burn-induced ischaemia and oedema. A 1 cm2 full
      thickness burn was made in the skin of 20 rats with a hot aluminium rod followed
      by infusion of 1,2,6-IP3 (60 mg.kg.-1 h-1) or isotonic saline (n = 10 in each
      group). One hour later Evans blue was injected intravenously. Colour photographs
      of the area of the burn were taken in a standard manner before the burn and at
      intervals for three hours afterwards. The photographs were analysed by digital
      image colour analysis using normalised red-green-blue values. The increase in
      normalised blue values between 60 and 180 minutes after the burn was
      significantly reduced in animals treated with 1,2,6-IP3 compared with control
      animals (p < 0.001). Spectrophotometric analysis of extravasated Evans blue in
      the skin 180 minutes after the burn showed that it had been significantly
      inhibited by treatment with 1,2,6-IP3 (p < 0.001). In conclusion, digital image
      analysis allowed repeated evaluation over time and confirmed previous data about
      the ability of 1,2,6-IP3 to inhibit extravasation of plasma after burns.

PMID- 9646363
TI  - Contraction and myofibroblasts in restored skin.
AB  - Myofibroblasts and the contraction of split skin-graft donor sites were studied
      in 18 patients. For each patient five samples were studied, taken on days 0, 14,
      21, 28, and 35. On each occasion the extensions and densities of myofibroblasts
      were calculated. After the initial measurement, the subsequent extensions were
      expressed in percentages of the first, resulting in mean measurements of 100, 95,
      97, 99, and 99%, respectively. The myofibroblasts in 10 dermic fields were
      counted under light microscopy at a magnification of 1000 marked with anti-alpha
      smooth muscle actin antibodies using immunoperoxidase, resulting in the means of
      0.2, 3.8, 1.3, 1.3, and 0.4, respectively. The contraction and the increase in
      density of myofibroblasts were transitory and significant in the samples measured
      on day 14, but in sample 35 neither of the variables was significantly different
      from the initial sample. These variables evolved concurrently, corroborating the
      hypothesis that myofibroblasts are responsible for the contraction.

PMID- 9646364
TI  - Reinnervation of split skin grafts in humans: comparison of two different methods
      of operation.
AB  - Studies on the reinnervation of split skin grafts have produced contradictory
      results. As the difference in sensitivity may be caused by the method of
      grafting, sensory reinnervation was studied in split skin grafted by two
      different methods. Thirty-nine patients given split skin grafts after the
      excision of malignant melanoma took part in the study. In 17 patients, split skin
      was grafted on to the intact muscle fascia. In another 22 patients the skin was
      grafted directly on to the muscle after the fascia had been removed. In all
      patients, sensitivity (to touch, heat/cold, and pain) was tested on the grafts
      and the skin from the opposite side. Sensory functions on grafted skin were
      generally reduced. Patients with split skin grafted on to the intact muscle
      fascia had better reinnervation than the ones in whom the fascia had been
      removed. However, individual patients from both groups showed surprisingly good
      reinnervation of transplanted skin. The reasons for this finding are not clear,
      but it is quite possible that the characteristics of the grafted skin have some
      influence on the reinnervation.

PMID- 9646365
TI  - Closure of large pharyngo-oesophageal fistulas with free flap transfer after
      resections for cancer.
AB  - Postoperative salivary fistulas still remain a serious and potentially lethal
      problem in head and neck reconstruction particularly if the fistula is large and
      involving one half or more of the circumference of the pharyngo-oesophagus.
      Pedicled flaps have traditionally been the flaps of choice for closure of these
      fistulas, but the results are often disappointing. During the period 1982 to
      1995, we have used either a radial forearm free flap or a jejunal free flap to
      close large and complex pharyngo-oesophageal fistulas after resection for cancer
      in 15 patients. Although two patients developed major fistulas that required
      additional operations for closure, successful closure was achieved in all but one
      case: the success rate was therefore 14/15 (93%). We consider that jejunal flaps
      are suitable for circumferential pharyngo-oesophageal reconstruction and forearm
      flaps for non-circumferential defects.

PMID- 9646366
TI  - Free flap transfers for the treatment of osteomyelitis of the lower leg.
AB  - Since 1974, 31 cases of soft tissue defects associated with osteomyelitis of the
      lower leg have been treated by free flap transfer and followed up for more than
      three years. Four patients developed recurrences. Two of them were reoperated on
      and healed well. One patient was reoperated on three times, but remained
      infected. One patient developed a fever, but improved after intravenous infusion
      of antibiotics. Of the eight patients who underwent vascularised muscle transfer
      to the dead space created by saucerisation of the osteomyelitis, none developed
      signs of recurrence. By contrast, the four patients who developed recurrences
      were those in whom the dead space could not be completely filled with the free
      flap. It therefore seems important that after saucerisation, well-vascularised
      soft tissue should be used to pack the dead space completely to prevent
      recurrence of the osteomyelitis.

PMID- 9646367
TI  - Use of intraperitoneal vessels in reconstructive microsurgery: an account of 117
      cases.
AB  - The purpose of this study was to evaluate our experience of microvascular
      anastomosis of intraperitoneal vessels. Between 1985 and 1994, 117 microsurgical
      reconstructions were done using intraperitoneal vessels. These included
      oesophageal reconstruction (n = 106), reconstruction of the hepatic arterial,
      superior mesenteric arterial, or portal venous system (n = 8), and reconstruction
      of the chest or abdominal wall (n = 3). We used 129 intraperitoneal arteries and
      117 intraperitoneal veins. Of a total of 246 intraperitoneal vessels, five
      hepatic arteries, seven splenic, 14 gastroepiploic, six superior mesenteric, 178
      jejunal, 30 ileocolic, four middle colic arteries or veins, and two portal veins
      were used for microvascular anastomosis. The overall successful rate for these
      reconstructive cases was 97% (114/117). Microsurgical use of intraperitoneal
      vessels is a safe and developing procedure in plastic and reconstructive surgery.

PMID- 9646368
TI  - Classification, recording, and cleft palate surgery at the Uppsala Cleft Palate
      Centre.
AB  - This paper describes the classification system, method of recording, and surgical
      techniques used in Uppsala for children with isolated cleft palate. The
      classification is based on the system described by Kernahan and Stark and the
      more detailed system described by the American Cleft Palate Association.
      Separation of the hard palate into thirds, and into right and left sides, assures
      a detailed description of the cleft, and separates small morphological
      differences. The longitudinal registration system was introduced into the Uppsala
      Cleft Palate Centre in 1967. After the initial recording at the time of primary
      surgery, it is repeated at 5, 8, 11, 14, 17, and 20 years. By emphasising the
      therapeutic aspects of various stages of growth, it has been possible to limit
      the recording to once every third year. This has resulted in an important
      reduction in the dose of radiation without compromising the reliability of the
      results. Children born before 1975 had clefts of both the soft and hard palate
      closed at 18-24 months in a one-stage procedure. For children born in 1975 and
      later a two stage technique has been used, while clefts limited to the soft
      palate only have been closed entirely in the first operation. At first, the soft
      palate cleft was closed at 18 months of age and the hard palate at 4 to 5 years.
      The timing was changed in several steps to the present soft palate closure at 6
      months and hard palate closure at 2 years of age.

PMID- 9646369
TI  - Morphology of isolated cleft palate in children, including Robin sequence,
      treated with one or two-stage operations.
AB  - A classification developed at the Uppsala Cleft Palate Centre was used to
      describe isolated cleft palate in children with and without Robin sequence. The
      study included 109 patients born between 1968 and 1983 with isolated cleft
      palate. In 46 patients the cleft was closed in a single operation and 63 were
      treated by a two-stage procedure. Of the 109 patients 70 (64%) were girls. In 19
      patients (17%), the cleft was limited to the soft palate. Ninety of the patients
      had clefts of the hard palate and in 39 (43%) of these patients the clefts
      involved less than a third of the hard palate. Only four children (4%) had total
      clefts of both the hard and soft palate. The Robin sequence was diagnosed in 14
      children (13%), and it was more common in boys with isolated cleft palate (7/39;
      18%) than in girls (7/70; 10%). In those with Robin sequence the cleft was U
      shaped anteriorly in nine (64%), with great variations in width. Generally,
      however, the clefts were wider than other clefts involving the hard palate. In
      all cases, closure of the soft palate was followed by a spontaneous reduction in
      the width of the remaining cleft in the hard palate. The greatest improvement was
      noted in subjects with the U-shaped clefts, in whom the position of the tongue
      probably had the greatest influence on the development of wide primary clefts. In
      10 subjects with clefts of the soft palate only and 12 patients in whom the cleft
      included part of the hard palate (35%), only the first operation of the two-stage
      procedure was done because there was no residual cleft. In these subjects the
      original cleft had involved less than a third of the length of the hard palate.

PMID- 9646370
TI  - Dental abnormalities and ectopic eruption in patients with isolated cleft palate.
AB  - The aim of this study was to evaluate the influence of cleft size and surgical
      treatment on the development of permanent teeth in patients with isolated cleft
      palate. The series comprised 109 children with isolated cleft palate, 70 girls
      and 39 boys, including 14 patients with Robin sequence. The patients were grouped
      according to the sagittal extent of the palatal cleft, measured on dental casts
      obtained before the primary palate surgery. Forty-six children were treated by
      one-stage palatoplasty, and 63 in two stages. The dentition was studied on
      orthopantomograms taken at 5, 8, 11, and 14 years of age. Congenitally missing
      permanent teeth (third molars excluded) were found in 33 subjects (30%). Children
      with large clefts had significantly more missing teeth than children with small
      clefts. The tooth most usually missing was the mandibular second premolar,
      followed by the maxillary lateral incisor, and the upper second premolar. The
      incidence of dental malformation was 23%, mostly mild forms. Ectopic eruption of
      the upper first permanent molars was seen in 23 (45%) of the subjects with large
      clefts, and in 18 (31%) of those with small clefts. The surgical method did not
      significantly affect the direction of the eruption. There is a correlation
      between cleft size and hypodontia, dental deformity, and ectopic eruption.
      Children with Robin sequence had almost the same incidence of hypodontia,
      malformed teeth, and ectopic eruption as children with large clefts. There was no
      correlation between surgical method and ectopic eruption of the maxillary first
      permanent molars.

PMID- 9646371
TI  - Use of titanium dental implants as an integrated part of a CLP protocol.
AB  - The problem of edentulousness in the cleft area of patients with cleft lip and
      palate was formerly resolved with a conventional fixed bridge construction, but
      this approach did not always prove optimal. Nowadays, in these patients the
      bridge can be substituted by a crown on an osseointegrated titanium implant
      fixture. The concept of dental rehabilitation using titanium implants has
      gradually merged into our routine treatment for patients with cleft lip and
      palate. In this report we describe our surgical technique using osseointegrated
      titanium implants and evaluate our result in patients with cleft lip and palate.
      Sixteen patients with cleft lip and palate, 11 men and five women, were divided
      into two groups: group 1 consisted of six patients who did not need bone grafting
      prior to the fixture installation, and group 2 comprised 10 patients who had
      additional bone grafting three months before the fixture installation. Abutments
      were applied six months after fixture installation. Dental crowns and fixed
      bridges were then constructed. All patients were seen on regular follow-up
      visits. Routine roentgenograms were obtained preoperatively and when the
      abutments were applied. Photographs were taken at these occasions and also after
      the prosthodontic work was completed. Of a total of 31 fixtures, all except two
      were osseointegrated at the time of the abutment connection, and the remaining 29
      have all been functional during the observation period, giving a success rate of
      93%. In group 1 all fixtures (100%) were osseointegrated. The non-integrated
      fixtures were found in group 2 giving a success rate of 91% in this group. The
      mean follow-up time after fixture installation was six years and three months,
      and the mean observation time with loaded fixtures was five years and six months.

PMID- 9646372
TI  - Perforating branches: important contribution to the formation of the dorsal
      metacarpal arteries.
AB  - The perforating branches that originate from the deep palmar arch of the hand
      have been studied to provide a complete anatomical description of these vessels
      and assess their importance in the blood collateral pathway of the hand. We
      injected latex into the arteries of 50 cadaveric hands of 25 adults, of both
      sexes, all of Brazilian origin. These were dissected under a stereoscopic
      microscope. The perforating branch of the second interosseous space originated
      from the deep palmar arch in 80% of the cases, and it corresponded to the radial
      artery passing through the second space in 16%; the one of the third interosseous
      space originated from the deep palmar arch in 76% of the cases and from the
      palmar metacarpal artery of the third interosseous space in 16%; the one of the
      fourth interosseous space originated from the deep palmar arch in half the cases,
      from the deep palmar branch of the ulnar artery in 14%, and from the palmar
      metacarpal artery of this space in 18%. The perforating branch of the second
      space anastomosed with the second dorsal metacarpal artery (DMA) in 60% of the
      cases and formed it in 10%; the one of the third space anastomosed with the third
      DMA in 20% and formed it in 64%; the one of the fourth space anastomosed with the
      fourth DMA in 8% and formed it in 78%. These vessels are an important anastomotic
      pathway between the dorsal carpal network and the deep arteries of the hand and
      are important in the supply to the dorsum.

PMID- 9646373
TI  - Tissue expansion of a tube flap during the last transferring stage in
      reconstructions of the face and neck.
AB  - The tube flap technique is an old and safe distant flap for soft tissue
      reconstruction, and tissue expansion is a well known way of repairing adjacent
      soft tissue defects. We have experience of expanding a tube flap during the last
      transferring stage for reconstruction of the face and neck after a burn. The tube
      flap from the right acromiopectoral region, of which the two pedicled stumps had
      been transferred to the face and neck separately, was successfully extended to
      double its length in 17 days without changing the diameter of the flap by placing
      a tissue expander under the tube flap. The tube flap tolerates tissue expansion
      well, even after the pedicles of the flap have been transplanted to new
      positions. In this way, a tube flap can be enlarged by tissue expansion when it
      is used in certain cases of reconstruction.

PMID- 9646374
TI  - Mycotic aneurysm in a free flap.
AB  - A 41-year-old man developed a 3 x 4 cm wound after corrective osteotomies of his
      distal tibia and fibula. The wound was debrided and covered with a free gracilis
      muscle flap. Seven days after flap transfer, the arterial pedicle ruptured
      adjacent to the anastomosis. Attempted repair of the aneurysm failed and the
      graft was subsequently debrided. Intraoperative wound cultures grew Pseudomonas
      and Enterobacter cloacae, which were attributed to formation of the aneurysm.

PMID- 9646376
TI  - Establishing a polysomnography laboratory in India: problems and pitfalls.

PMID- 9646375
TI  - Lipofibromatous hamartoma (neural fibrolipoma) of a flexor nerve of the index
      finger.
AB  - A 24 year old woman presented with a painless fusiform mass in her right index
      finger. Exploration showed an enlargement of the nerve by fibrofatty tissue and
      microsurgical intraneural dissection was done. Histological examination
      identified the lesion as a lipofibromatous hamartoma of the nerve, which is both
      rare and benign. There are different options for treatment of this lesion.

PMID- 9646377
TI  - Sleep position and sleep stages: evidence of their independence.
AB  - Recently we conducted a first ontogenetic study of sleep positions in the human,
      which involved five groups of 10 subjects (5 males, 5 females) from each of the
      following age categories: 3-5 years, 8-12 years, 18-24 years, 35-45 years, 65-80
      years. They slept for 4 consecutive nights in the laboratory. Sleep positions
      were recorded during 2 nights with super-8 time-lapse photography. In a first
      report we presented results showing developmental trends in sleep position
      shifts, position durations and in the use of prone, supine and side positions. In
      the current report we present results showing that there was no significant
      relationship between sleep stages and sleep positions in any group. Furthermore,
      time-series analyses revealed no consistent pattern of position sequences in any
      of the age groups. It is concluded that, while there are ontogenetic trends in
      sleep position preferences, sleep positions are independent of sleep stages and
      do not show consistent rhythmicity.

PMID- 9646378
TI  - Effects of sleeping position and time after feeding on the organization of
      sleep/wake states in prematurely born infants.
AB  - Epidemiologic studies provide strong evidence for the conclusion that sleeping in
      the prone position places infants at greater risk for sudden infant death
      syndrome (SIDS). Prior studies in newborn infants found that in the prone
      sleeping position there is less time awake and more quiet sleep, but little
      change in the amount of active sleep. To determine whether the effects of
      sleeping position on state distribution vary with time after feeding, we studied
      prematurely born infants in both the prone and supine sleeping positions. Sleep
      states were recorded each minute during interfeed intervals. Results demonstrate
      expected effects of sleep position on state distribution: prone sleeping is
      associated with a 79% increase in quiet sleep and a 71% decrease in time awake.
      While the decreases in time awake are seen throughout the interfeed interval,
      increases in quiet sleep in the prone position are found only within the first
      hour and again near the end of the interfeed interval. These results are
      consistent with the hypothesis that prone sleeping could increase risk for SIDS
      by altering the organization of sleep, and that time after feeding may play an
      important role in the expression of these effects.

PMID- 9646379
TI  - Effect of age on EEG arousals in normal sleep.
AB  - EEG arousals were quantified in 40 nocturnal polysomnographic recordings
      belonging to four age groups (teenagers: 10 to 19 years; young adults: 20 to 39
      years; middle-aged: 40 to 59 years; elderly: > or = 60 years). Ten subjects (five
      males and five females) participated in each group. The subjects were healthy and
      sound sleepers. All sleep recordings were preceded by an adaptation night which
      aimed at excluding the presence of sleep-related disorders. The recordings were
      carried out in a partially soundproof recording chamber and in a standard
      laboratory setting. Arousal indices (AI), defined as the number of arousals per
      hour of sleep, were calculated for total sleep time (AI/TST) and for all the
      sleep stages. AI/TST increased linearly with age (r = 0.852; p < 0.00001):
      teenagers (13.8), young adults (14.7), middle-aged (17.8), elderly (27.1). An age
      related positive linear correlation was found also for the arousal indices
      referred to NREM sleep (r = 0.811; p < 0.00001) and to stages 1 and 2 (r = 0.712;
      p < 0.00001), while in stages 3 and 4 and in REM sleep, arousal indices showed
      stable values across the ages. Overall, arousals lasted 14.9 +/- 2.3 seconds,
      with arousal duration stable across the ages (range of means: 13.3-16.6 seconds)
      and no relevant differences between NREM sleep (14.6 +/- 2.5 seconds) and REM
      sleep (16.2 +/- 5 seconds). The paper discusses the impact of age on arousals,
      the similarities between arousals and the phases d'activation transitoire, and
      the consideration that arousals are physiological components of sleep.

PMID- 9646380
TI  - The consequences of a week of insomnia. II: Patients with insomnia.
AB  - Insomnia patients present with a consistent set of complaints that they generally
      report as secondary to their poor sleep, including increased tension/confusion,
      decreased vigor, personality disturbance, subjective overestimation of poor
      sleep, increased body temperature, increased 24-hour whole-body metabolic rate,
      and longer MSLT latencies. If there is a relationship between the poor sleep and
      the secondary symptoms, then particularly poor sleep should exacerbate those
      symptoms. Ten patients with insomnia were identified on the basis of a 2-night
      screening protocol, then slept in the laboratory for 10 additional nights. On 7
      of the nights, the insomnia patients had their wake-after-sleep-onset increased
      so that their total sleep time was 80% of that on their second screening night,
      resulting in an average of 254 minutes (of 480 minutes in bed) of sleep. The
      spectrum of changes seen in these patients with insomnia who had very poor sleep
      for a week was characteristic of mild partial sleep deprivation, and not
      consistent with exacerbation of symptoms found in patients with primary insomnia.
      Specifically, (1) these patients had a reduction as opposed to an increase in the
      MSLT values, but the MSLT values at the end of the week remained within normal
      limits; (2) these patients had decreased (as opposed to increased) whole
      metabolic rate following nights of particularly poor sleep; (3) these patients
      tended to underestimate (rather than overestimate) their subjective sleep latency
      while being given particularly poor sleep; and (4) these patients displayed no
      significant change in body temperature, subjective anxiety, or MMPI scores
      following particularly poor sleep. It was concluded that the secondary symptoms
      reported by patients with primary insomnia are probably not related to their poor
      sleep per se. Data from previous studies that varied physiological arousal were
      used to support the contention that the secondary symptoms of patients with
      insomnia, and perhaps the poor sleep itself, occur secondary to central nervous
      system hyperarousal.

PMID- 9646381
TI  - Iron and the restless legs syndrome.
AB  - STUDY OBJECTIVES: Using blinded procedures, determine the relation between serum
      ferritin levels and severity of subjective and objective symptoms of the restless
      legs syndrome (RLS) for a representative patient sample covering the entire adult
      age range. DESIGN: All patient records from the past 4 years were retrospectively
      reviewed to obtain data from all cases with RLS. All patients were included who
      had ferritin levels obtained at about the same time as a polysomnogram (PSG), met
      diagnostic criteria for RLS, and were not on iron or medications that would
      reduce the RLS symptoms at the time of the PSG. SETTING: Sleep Disorders Center.
      PATIENTS: 27 (18 females, 9 males), aged 29-81 years. INTERVENTIONS: None.
      MEASUREMENTS AND RESULTS: Measurements included clinical ratings of RLS severity
      and PSG measures of sleep efficiency and periodic limb movements (PLMS) in sleep
      with and without arousal. Lower ferritin correlated significantly to greater RLS
      severity and decreased sleep efficiency. All but one patient with severe RLS had
      ferritin levels < or = 50 mcg/l. Patients with lower ferritin (< or = 50 mcg/l)
      also showed significantly more PLMS with arousal than did those with higher
      ferritin, but the PLMS/hour was not significantly related to ferritin. This last
      finding may be due to inclusion of two 'outliers' or because of severely
      disturbed sleep of the more severe RLS patients. CONCLUSIONS: These data are
      consistent with those from a prior unblinded study and suggest that RLS patients
      will have fewer symptoms if they have ferritin levels greater than 50 mcg/l.

PMID- 9646382
TI  - Sleep and pulmonary function in children with well-controlled, stable asthma.
AB  - The aim of this study was to assess sleep and pulmonary function in asthmatic and
      control children. Forty children with well-controlled, stable asthma, and 34
      controls (age range: 8.2 to 15.4 years) were monitored with wrist actigraphs and
      peak-flow meters for 3 consecutive days. In addition, asthma severity was
      assessed by subjective parental and self-rating scale and symptom checklist.
      Asthmatic children had poorer sleep quality in comparison to their controls, as
      manifested in lower percentages of quiet sleep (p < .05) and increased activity
      level during sleep (p < .05). As expected, asthmatic children had reduced morning
      peak expiratory flow measures (p < .01) and a higher evening-to-morning drop in
      peak expiratory flow (p < .005). Peak-flow measures were significantly correlated
      with subjective and objective sleep measures. In the asthmatic group, sleep
      measures were also correlated with subjective asthma severity indices and symptom
      checklists. We conclude that poorer sleep is associated with reduced pulmonary
      function. The reduced sleep quality, coupled with subjective reports of increased
      fatigue and reduced alertness found in asthmatic children, suggest that these
      children are at risk for developing neurobehavioral deficits associated with
      chronic sleep loss.

PMID- 9646383
TI  - Importance of the pulse oximeter averaging time when measuring oxygen
      desaturation in sleep apnea.
AB  - The accuracy of pulse oximeters in measuring transient changes in oxygen
      saturation (SaO2) may be affected by the oximeter time response. The aim of this
      study was to assess the effect of modifying the pulse oximeter averaging time (T)
      on the measurement of SaO2 in patients with the sleep apnea-hypopnea syndrome
      (SAHS). Twelve patients with severe SAHS were studied during a nap with
      conventional oximeters: Ohmeda 3740 and Criticare 501. We compared the readings
      of each patient's oxygen desaturation measured simultaneously with two identical
      pulse oximeters. One oximeter was the control (T = 3 seconds), and in the other T
      was set from 3 seconds to 21 seconds. No significant differences in SaO2 were
      found when both oximeters were set to the same T (3 seconds). In contrast,
      increasing T to 12 seconds and 21 seconds in one of the oximeters resulted in
      considerable and significant differences in the measured SaO2: oxygen
      desaturation was underestimated by up to 60% when compared with the control. The
      misestimation of SaO2 induced by settings of T which are within the range
      selectable in conventional oximeters may be of epidemiological significance when
      pulse oximetry is used as a complementary diagnostic tool to classify sleep
      events in SAHS.

PMID- 9646385
TI  - New rationales and methods for quantitative dream research outside the
      laboratory.
AB  - Laboratory studies of dreams are now at a low ebb, but past laboratory studies
      provide a basis for the belief that some kinds of non laboratory studies, those
      that focus strictly on dream content, may be useful for scientific purposes.
      Further, the collection of Most Recent Dreams from individuals in specific types
      of groups, along with the use of dream journals from individuals, can supply the
      necessary sample sizes needed for reliable findings (100-125 for groups, 75-100
      for individuals). An Excel 5 spreadsheet has improved the accuracy and speed of
      data analysis with the well established and widely used Hall/Van de Castle coding
      system and is available on the World Wide Web. A bar graph called the h-profile,
      based on percentage deviations from norms and generated automatically by the
      Excel 5 spreadsheet, makes it much easier to grasp comparisons of different
      groups or individuals on many content indicators. Findings with the Hall/Van de
      Castle system showing age, gender, individual, and cross-cultural similarities
      and differences suggest that these new methods of data collection and analysis
      provide a valid and low-budget way to further the understanding of dream content.

PMID- 9646384
TI  - Cognitive executive dysfunction in patients with obstructive sleep apnea syndrome
      (OSAS) after CPAP treatment.
AB  - We have previously described impairments of cognitive executive functions in 17
      patients with OSAS in comparison with 17 normal controls, as assessed by various
      frontal-lobe-related tests. In the present study, 10 of these OSAS patients
      treated with continuous positive airway pressure (CPAP) were reevaluated after 4
      6 months of treatment. Neuropsychological tasks explored attention, short-term
      memory span, learning abilities, planning capacities, categorizing activities,
      and verbal fluency. Patients were found to have normalized most of their
      cognitive executive and learning disabilities, but all the short-term memory
      tests remained unchanged. These findings are discussed in light of the
      contribution of the frontal-lobe-related systems to short-term memory functions,
      and the eventual pathogenic role played by sleep fragmentation and nocturnal
      hypoxemia, which are related to the occurrence of apneic and hypopneic events. In
      conclusion, short-term memory impairment was persistent in OSAS patients despite
      CPAP treatment for 4-6 months.

PMID- 9646386
TI  - Presentation and reading level of sleep brochures: are they appropriate for sleep
      disorders patients?
AB  - OBJECTIVE: Sleep-disorders patients must be given information and health
      education they understand. The purpose of this study was twofold: (1) to assess
      suitability of American Sleep Disorders Association and National Sleep Foundation
      patient education brochures; and (2) to assess one widely used brochure, using
      patient input and patient literacy level, as a model for development of future
      materials. DESIGN: Twelve American Sleep Disorders Association and National Sleep
      Foundation brochures were assessed for reading level using Grammatik, and for
      design, presentation, and motivating qualities using the Suitability Assessment
      of Materials (SAM). Patient literacy level was assessed using the Rapid Estimate
      Of Adult Literacy in Medicine (REALM). SETTING: The Louisiana State University
      Medical Center sleep clinic, faculty private sleep clinic, and in the sleep
      center laboratory. PATIENTS OR PARTICIPANTS: During the months of February-May
      1997, 170 sleep disorders patients, 39% African American, 59% white participated
      in the study. Participants ranged in age from 18-73 years, with a mean age of 46.
      MEASUREMENTS AND RESULTS: Suitability scores for the 12 brochures indicate that
      none scored in the superior range, 83% scored adequate, and 17% scored not
      suitable. Ninety-four percent of the brochures were written on a 12th grade level
      or higher, yet 37% of the sleep patients tested were reading at less than a 9th
      grade level. Low-level readers were significantly more likely than their higher
      reading-level counterparts to report that a brochure was too long (22% vs 12%; p
      < .05), and that they would need help reading it (44% vs 3%; p < .001).
      CONCLUSIONS: Patients need sleep information given to them on a level they
      understand. When developing and selecting appropriate materials, reading level,
      length, and suitability of written material should be considered.

PMID- 9646387
TI  - Tunnel restorations in permanent teeth. A 7 year follow up study.
AB  - The aim of the study was to perform a long-time evaluation of tunnel restorations
      made in a general dental practice concerning survival time and type of failures.
      267 Class I (87%) and II (13%) tunnel restorations in permanent teeth on 193
      patients--mostly teenagers and young adults--were evaluated at annual recalls.
      The observation time-span was 1-7 years. The restoration material was a
      conventional glass ionomer cement in Class I tunnels and a silver cermet glass
      ionomer cement in Class II tunnels. The yearly failure rate was 7% and the 50%
      survival time was 6 years. The reasons for replacement were: marginal ridge
      fracture (41%), recurrent caries (40%) and cavitation in approximal enamel (19%).
      No differences in failure rate between Class I and II tunnels could be seen, but
      recurrent caries was more frequent in Class I tunnels. Restorations made during
      the second year of the study were more successful, indicating a learning effect.
      Class I tunnel restorations in general practice can be an alternative to
      conventional Class II restorations with narrow indications, i.e. patients with
      relatively low caries activity, small approximal lesions in combination with
      small demineralization zones in the enamel wall.

PMID- 9646389
TI  - An experimental rabbit model for studying the healing of onlay bone grafts.
AB  - An experimental rabbit model for studying the incorporation of onlay bone grafts
      is described. Bone grafts from radius served as the graft and were positioned
      beneath the mandibular basis. Six rabbits were used in the study and healing
      periods of 6 weeks and 6 months were used. Each animal was operated twice and in
      this way the grafts could be followed for six weeks on one side and for 6 months
      on the contralateral side of the mandible. Healing of the bone graft with bony
      union to the mandibular base with cortical bone in contact with cortical bone was
      encouraging. Remodelling of the graft was observed after 6 weeks but was even
      more pronounced after 6 months. After 6 weeks osteoclastic/osteoblastic activity
      was primarily observed in the graft-recipient contact area and in the
      intracortical compartment of the grafted bone. The resorption was most pronounced
      in the borderlines of the graft. It is concluded that the described experimental
      model can serve as a useful method for the study of onlay bone graft healing and
      interaction between implants and bone transplants.

PMID- 9646388
TI  - Risk factors for dental caries in 2-year-old children.
AB  - This paper describes risk factors for dental caries identified among 491 2-year
      olds in the city of Umea, Sweden. The study was performed as a risk screening for
      dental caries according to a method developed for use by dental assistants. The
      sugar consumption was high, 80% of the 2-year-olds had sweets once a week or more
      and 25% had sweet beverages once a day or more frequently. In addition, 14% of
      the children had a meal at night and most common were formula, bovine milk or
      breastmilk. The majority of the parents brushed the child's teeth at least daily
      using fluoride toothpaste. Among the children 6% had a chronic somatic disorder
      and 6% had an intolerance towards specific foods, milk being the most common. The
      high level of sugar consumption indicates that improved dental health education
      focusing on the importance of limiting sugar consumption is needed among parents
      with young children.

PMID- 9646390
TI  - Hand dermatitis and symptoms from the fingers among Swedish dental personnel.
AB  - Hand dermatitis among dental personnel has been an issue in recent years. Dental
      personnel manually handle polymer materials which are known to irritate skin, and
      also cause allergy. In addition, dental personnel wash their hands frequently,
      and use latex gloves, and are therefore at risk to develop hand dermatitis. To
      survey the occurrence of hand dermatitis among dental personnel, questionnaires
      were sent to all dental teams (dentist + chair assistant) working in the two
      northern Swedish counties. Referents were; researchers, teachers, and secretaries
      from a university and high schools, from the same geographical area. The response
      rate was 76% for dental teams, and 66% for referents. The results show that male
      dentists reported a significantly higher prevalence of hand dermatitis than male
      reference. In contrast to chair assistants and referents, dentists (both male and
      female) reported a higher extent of hand dermatitis on the left than on the right
      hand. There was an association between hand dermatitis among dental personnel
      and; age, eczema in childhood, and hay fever but, not with; sex, asthma, frequent
      washing of the hands, and glove use. Whitening of the fingers increased with
      increasing age among dental personnel. Pricking was also associated with frequent
      glove use. Pricking of the fingers was associated with sex, and 3.5 times more
      common among female dental personnel than male dentists. Numbness of the fingers,
      and finger pain was reported by more dentists than chair assistants and
      referents.

PMID- 9646391
TI  - Adverse health reactions in skin, eyes, and respiratory tract among dental
      personnel in Sweden.
AB  - Dental personnel manually handle products that contain monomers. Several studies
      have documented adverse health effects after exposure to such products. Gloves
      made of vinyl or latex are easily penetrated by monomers. Ordinary glasses, or
      visors, do not protect against vapour from polymer products. Dental face masks
      filter out about 40% of respirable particles. To survey the prevalence of asthma,
      atopic dermatitis, conjunctivitis, hay fever/rhinitis, and hand eczema among
      dental personnel, a questionnaire was distributed to all dental teams in Northern
      Sweden. Referents were researchers, teachers, and secretaries from the same
      geographical area. The response rate was 76% for dental teams, and 66% for
      referents. The results show a significantly higher prevalence of conjunctivitis,
      and atopic dermatitis among dentists, both male and female. Hypersensitivity to
      dental materials was reported by significantly more dental personnel than by
      referents.

PMID- 9646392
TI  - Type of treatment and estimation of time spent on dental trauma--a longitudinal
      and retrospective study.
AB  - The consequences of traumatic tooth injuries (dental trauma) are time-consuming
      and costly treatment and follow-ups, of which our knowledge is scarce.
      Consequently the aim of the present study was to measure the total time of
      treatment of uncomplicated and complicated traumas to primary and permanent
      teeth. The study was performed in three steps based on a randomly selected sample
      of Danish children and adolescents living in the municipality of Copenhagen,
      Denmark: (I) A descriptive analysis of traumas affecting 106 children and
      adolescents all born in 1970 and randomly chosen among the total number of
      patients treated. Treatments took place between 1972 and 1988. (II) A study of
      the time and frequency of different types of emergency and planned treatment
      estimated by 14 dentists employed by the municipal dental service. (III)
      Calculation of the total treatment time on the basis of the results from (I) and
      (II). The most common traumas were luxations of primary teeth and fractures of
      permanent teeth. The most frequent treatments dealt with were uncomplicated crown
      fractures and luxations followed by other different diagnoses of complicated
      traumas. The treatment time for primary teeth for uncomplicated traumas were used
      mostly for information, while the time for complicated traumas was used for
      follow-ups. The treatment time for traumas to permanent teeth was dominated by
      follow-ups, irrespective of the complication status. Only 3% of uncomplicated
      traumas of permanent teeth resulted in endodontic treatment, compared to 67% with
      complicated traumas. Uncomplicated traumas to primary teeth required a total of
      2.5 visits and 0.8 hrs treatment time, while 4.3 visits and 1.6 hrs per
      individual were used for complicated traumas. For permanent teeth with
      uncomplicated traumas 9.2 visits and 3.2 hrs were required, and for complicated
      traumas 16.4 visits and 8.5 hrs per individual. The respective treatment times
      for complicated traumas for primary and permanent teeth were 2.0 and 2.7 times
      higher, compared to the corresponding uncomplicated traumas. There were no gender
      differences in type of injury and number of visits for injuries to primary and
      permanent teeth.

PMID- 9646393
TI  - Ethical issues in dental management of patients with severe dementia: ethical
      reasoning by hospital dentists. A narrative study.
AB  - Dementia alters the patient's ability to accept conventional dental treatment and
      conflict situations arise involving moral dilemmans in judgements and actions.
      The aim of the study is to disclose how the dentists think, feel and act in such
      conflict situations and their ethical reasoning. Qualitative methods are used in
      interpretation of 21 tape-recorded narratives from hospital dentists. In all
      narratives, the problem emerged from uncertainty about what comprise an
      appropriate treatment. The ethical dilemma could either be narrated as internal,
      within the dentist or external between the dentist's opinion and opinions to the
      contrary from co-actors in the story. In a climate of restraints in public
      spending in health care a discourse from the perspectives of ethics is essential
      to ensure respect for human integrity in society, fundamental for all caring,
      including dental care of patient with dementia.

PMID- 9646394
TI  - The Swedish National Dental Insurance's periodontal diagnosis. Used on an
      individual level.
AB  - The Swedish National Dental Insurance Board requires a periodontal diagnosis (FKF
      2030 86.12GR) from general practitioners before treating patients, a process
      which is expensive. The Swedish National Dental Insurance-index (SNDI-index) is
      based on clinical data and radiographs and every tooth is assigned a rating
      between 0 and 4. From the time of introduction of the Swedish National Dental
      Insurance plan in 1974, data can have been collected for 1.7 million patients if
      the regulations were followed according to the Swedish National Dental Insurance
      Board in Stockholm, Sweden. It is of interest to examine whether all of these
      collected periodontal data reflect periodontal status. In this study includings
      56 individuals, the Swedish National Dental Insurance-index, used on an
      individual level, correlated significantly with the individual changes in bone
      support (as percent of toothlength) of the tooth in 1979 (rs = -0.80, t = -9.7, p
      < 0.001, ci 95% = -0.88(-)-0.68) as well as in 1989 (rs = -0.79, t = -9.5, p <
      0.001, ci 95% = -0.87(-)-0.67).

PMID- 9646395
TI  - Survival of onlay bone grafts. A study in the adult rat.

PMID- 9646396
TI  - On the prosthodontic patient. An investigation of factors influencing patient
      expectations and satisfaction with extensive prosthodontic care.

PMID- 9646397
TI  - Studies on fluoridated toothpicks.
AB  - The aim of this thesis was to evaluate the wooden toothpick as a vehicle for the
      delivery of fluoride to the approximal area. After two minutes use in vivo, the
      release of fluoride from the pointed section of a toothpick impregnated in 4% NaF
      was estimated to 0.15 mg. Toothpicks produced similar or somewhat higher fluoride
      concentrations in the approximal area compared with other fluoride-containing
      products, like dentifrice, mouthrinse solution and tablet. The mean fluoride
      concentration in an approximal area treated for two minutes with a toothpick
      impregnated in 4% NaF was around 11 mM/l. Toothpicks impregnated in 4% NaF, 8%
      SnF2 or 2% chlorhexidine had an effect on the proportion of mutans streptococci
      and on the decline of pH in dental plaque, but it was small and only of short
      duration. The recolonization of mutans streptococci was, however, slower after
      using the SnF2- and chlorhexidine-impregnated toothpicks than after using the NaF
      and non-impregnated toothpicks. The effect of fluoridated toothpicks on the
      degree of de- and remineralization of enamel and dentine was measured using
      transversal microradiography in an in situ study. Four weeks' use of toothpicks,
      especially of NaF-impregnated toothpicks, reduced the degree of demineralization
      of enamel and dentine at approximal sites. Secondary ion mass spectrometry was
      also used to determine the fluoride content in the outer surface of dentine,
      which increased more than 10 times after using fluoride toothpicks compared with
      non-impregnated toothpicks. In a second in situ study, 4% NaF-, 2% chlorhexidine-
      and non-impregnated toothpicks had a similar effect on sound and demineralized
      enamel and on demineralized dentine. However, the NaF toothpicks were superior in
      terms of their effect on sound dentine. The effect on mutans streptococci and
      plaque-pH, on the other hand, was the same for all three types of toothpicks. The
      main conclusion from this thesis is that the wooden toothpick is a suitable
      vehicle for the delivery of fluoride to the approximal area.

PMID- 9646398
TI  - [Case report. Merino sheep, female, six years old].

PMID- 9646399
TI  - [Experiences with a theloresectoscope compared with conventional teat endoscopy
      in diagnosis and therapy of covered teat lesions].
AB  - In 30 dairy-cows, suffering from a covered teat lesion near the papillar duct
      and, as a result, from milk flow hindrance, two different methods of minimal
      invasive endoscopy for diagnosis and therapy were performed. In 15 patients
      (group I) the endoscope was inserted through the papillar duct and additionally
      through an artificial approach in the teat wall. Avulsions of mucosa could be
      visualized and resected with special instruments. In further 15 patients (group
      II) a new Theloresectoscope (teat-endoscope, combined with integrated
      radiosurgery-unit) was used for performance of endoscopy via papillar duct and
      lateral endoscopy. Mucosal avulsions were removed under visualization by means of
      radiosurgery without inserting an additional instrument through the papillar
      duct. Afterwards, after application of antibiotic drugs intramammarily, a natural
      teat canal insert (NIT) was administered in the papillar ducts of the 30 treated
      teats for seven days to keep the teat canal calm and wide. After three days the
      NIT was replaced and antibiosis refreshed. Eight days after endoscopy the
      temporary cessation of milking was canceled and the quarters were milked by
      machine. In two probands out of group I and three cows out of group II six weeks
      after first intervention lateral endoscopy was performed again for documentation
      of the healing process. In all 30 cases six weeks after resection of mucosal
      avulsions inquiries about the milking-quality were made by phoning the owners of
      patients. In 29 cows, still existing on the farms after six weeks, the milking
      comfort was considered as being good or, in few cases, satisfactory by the
      owners. Somatic cell count showed good results, though eight probands in group I
      and nine cows in group II presented positive results in the California-Mastitis
      Test. Comparing the two different endoscopic techniques used in this study, both
      methods appeared of same value concerning diagnosis of aberrations in bovine teat
      by means of endoscopy via teat canal. Differences were found in handling of
      instruments performing endoscopy with lateral, artificial approach: the novel
      Theloresectoscope is by far more useful in endoscopic surgery, because the
      surgical intervention can be performed by a single person, whereas using the
      conventional instruments in most cases a second person as an assistant for
      operation is required.

PMID- 9646400
TI  - [Comparison of two castration methods in cattle: plasma cortisol levels,
      leukocyte count and behavioral changes].
AB  - Two methods of castration (surgical and Burdizzo method) of male calves were
      compared by measuring plasma cortisol concentrations. Increased plasma cortisol
      values were found only during the first three hours after castration. There were
      no significant differences in plasma cortisol values and changes of behaviour
      between groups of surgical and Burdizzo castrated calves. Plasma cortisol values
      did not decrease during the first days after castration. The results suggest,
      that surgical and Burdizzo-castration do not differ in regard to pain.

PMID- 9646401
TI  - [Treatment of acute respiratory tract diseases in cattle with Bisolvon in
      combination with either enrofloxacin, cefquinome, ceftiofur or florfenicol].
AB  - The purpose of the present clinical studies was to determine the clinical
      efficacy of a combined parenteral and oral treatment with Bisolvon in combination
      with antibiotics in bovines suffering from acute respiratory disease. To this end
      four trials were conducted in respiratory diseased bovines; a total of 619
      animals were evaluated. The animals were randomly assigned to one of two
      treatment groups within each study and were treated either with enrofloxacin,
      cefquinome, ceftiofur or florfenicol. The Bisolvon group was additionally treated
      with Bisolvon over 5 consecutive days. Daily clinical examinations were carried
      out over a period of 6 days. The clinical respiratory score, the primary
      parameter, representing a summation of the scoring points for the parameters
      respiratory rate, nasal discharge, spontaneous coughing, lung sounds and grade of
      dyspnoea and the clinical index score, which additionally included the general
      parameters fever, demeanour and feed intake, were significantly lower in the
      Bisolvon groups compared to the controls at all examinations after initiation of
      therapy in all trials with the exception of day 2 in one study. Lower values
      correspond to a less severe clinical condition. This consistent result as well as
      the evaluation of the single parameters are indicative of an acceleration of the
      recovery of the animals additionally treated with Bisolvon.

PMID- 9646402
TI  - [Investigations on the development of hyponatremia in older calves with
      diarrhea].
AB  - The study involved 50 hospitalized calves (four weeks to five months old)
      suffering from diarrhoea and hyponatraemia (blood sodium concentration below 130
      mmol/l). Starting from the day of admission blood, urine, and faecal samples were
      taken each morning and sodium and potassium concentrations were measured. In
      addition, blood and urine samples were taken in the evenings, if electrolytes had
      been given orally during the day. The obtained values from urine samples were
      compared with the plasma concentrations in order to check for inadequate renal
      excretion of electrolytes. Consistency of the faeces and visible blood admixture
      were the main criteria in the evaluation of electrolyte concentration in the 317
      samples of faecal water. With one exception no inadequate renal losses of sodium
      were observed. Sodium and potassium concentrations in faecal water showed a
      distinct negative correlation. As the consistency of faeces grew increasingly
      normal, electrolyte contents of faeces approached those reported for adult
      cattle, i.e. potassium levels rose and sodium levels decreased. Visible blood
      admixtures had no significant effect on the sodium and potassium concentrations
      in the faeces. A distinct relationship between electrolyte contents in faecal
      water and the consistency of the faeces was found. There were highly significant
      differences in electrolyte concentrations between faeces of watery (Na: 82 +/- 21
      mmol/l; K: 23 +/- 12 mmol/l) and soupy (Na: 54 +/- 26 mmol/l; K: 42 +/- 19
      mmol/l) consistency (mean +/- standard deviation). By contrast, soupy and pulpy
      faeces just showed a slight or no difference in electrolyte concentrations. Only
      faeces of watery consistency contained approximately as much sodium as observed
      in neonatal calf diarrhoea. These results show that the pronounced hyponatraemia
      in older calves can hardly be attributed to loss of sodium via faeces and urine.
      The following possible causes are proposed: (a) older calves usually have access
      to water (therefore there is more gradual dehydration or no dehydration at all);
      (b) oral electrolyte solutions are seldom administered.

PMID- 9646403
TI  - [Fodder flinging in cattle].
AB  - When cattle fling fodder, this is, in many respects, an undesirable behaviour:
      fodder is wasted, the interior of the shed is dirtied and the slatted floor is
      compromised in its function. Through behavioural observation, it should therefore
      be examined which are the determining factors for fodder throwing. Two breeds of
      cattle (Simmenthal and Brown Swiss) were examined to establish how often the
      animals fling fodder within 60 minutes in the medium-tie-stall and the short-tie
      stall system and receiving varied feeding (green fodder and grass silage). Fodder
      throwing occurs amongst the two examined breeds, in both housing systems and
      amongst animals of all ages. The percentage of fodder flinging of Simmenthal cows
      was higher in the medium-tie-stall than in the short-tie-stall system (16.8% and
      8.3%; p < 0.01). During the initial period following the start of feeding, the
      throwing frequency was at its highest. Fodder throwing animals had a
      significantly higher blinking frequency (a sign of excitement) than those not
      flinging fodder (p < 0.01). The reasons for food flinging and its possible
      effects on the fodder were not checked. Nevertheless, consideration was given to
      the meaning of this behaviour pattern. It would seem it is not a behaviour
      disorder. It could be that food flinging is the result of a learning process to
      control an itch caused by the husbandry system.

PMID- 9646404
TI  - [Comparative histological investigations on the teats of sheep and goats].
AB  - In the present study the teats of the goat and the sheep were investigated light
      microscopically. In both species, smooth muscle elements condense towards the
      streak canal, and abundant arteries occur with thick tunica media and various
      valve structures. The apocrine sweat gland have a wide acinous element, which are
      regarded as a part of the excretory duct. Additional alveolar secretory tissue is
      present in the wall of the lactiferous sinus, which tubuloalveoli are probably of
      two varying types in the sheep and empty directly into the lumen of the
      lactiferous sinus in the goat. The histologic features of the teat in the goat
      differ mainly in the smaller and less coiled apocrine sweat glands, the thin
      stratum granulosum of the teat canal epithelium and the occurrence of
      supplementary canals (frequently two) in the initial part of the teat canal. The
      ovine teat shows a partly extremely thin epidermis, solid coiled apocrine sweat
      glands, and a pigmented epithelium of the teat canal equipped with a considerably
      thicker stratum granulosum.

PMID- 9646405
TI  - [Halicephalobus (Syn. Micronema) deletrix as a cause of granulomatous gingivitis
      and osteomyelitis in a horse].
AB  - Therapy resistant swellings of the maxillary region and unilateral nasal
      discharge in older horses are mainly thought to be consequences of neoplasias of
      the oral cavity, especially of the gingiva and the teeth, or to develop from
      tumours of the nasal cavity. We report an unilateral swelling of the left nasal
      and buccal region in a 13-year-old gelding, which was accompanied by an
      aggressive destruction of involved osseous tissue due to a severe proliferative
      granulomatous inflammation. The granuloma was caused by the nematode
      Halicephalobus (syn. Micronema) deletrix. This nematode infection is known for
      over 30 years, even though the here reported form is uncommon and rarely
      diagnosed. However, this report shows that even in cases of unilateral maxillary
      swellings in horses a granulomatous inflammation due to nematodiasis should be
      considered as an additional differential diagnosis.

PMID- 9646406
TI  - [Investigation of hematologic and clinical chemical parameters in serum of
      newborn fallow deer calves (Dama dama L.). Clinical chemical parameters].
AB  - 59 blood samples from newborn fallow deer calves were clinical-chemically
      investigated at day of birth. To estimate the metabolic situation post natum we
      measured the concentration of glucose (6.8 +/- 2.2 mmol/l), total protein (54.0
      +/- 8.7 g/l), albumin (19.5 +/- 2.3 g/l), gammaglobulins (3.5 +/- 2.0 g/l), urea
      (5.2 +/- 1.8 mmol/l), creatinine (86.2 +/- 22.8 mumol/l) and bilirubin (4.4 +/-
      4.4 mumol/l). Furthermore the activity of the enzymes AP (3258 U/l), ALAT (10.8
      U/)l, ASAT (67.2 U/l), GGT (82.2 U/l) and CK (181.0 U/l) was measured.
      Additionally following minerals were determined: sodium (135.8 +/- 10.2 mmol/l),
      chloride (95.6 +/- 7.5 mmol/l), potassium (4.3 +/- 0.6 mmol/l), calcium (2.6 +/-
      0.3 mmol/l), inorganic phosphor (2.4 +/- 0.5 mmol/l) and iron (12.1 +/- 8.0
      mumol/l).

PMID- 9646407
TI  - [Preliminary examinations on the effects of the breed characteristic feature
      "feather crest" on skull and brain anatomy of domestic ducks (Anas platyrhynchos
      f. dom.)].
AB  - As mentioned in older sources, the crested breed of the domestic duck is
      described as variety with high pre- and postnatal mortalities, malformations in
      skull and brain anatomy, and several central nervous deficiencies in affected
      birds. Therefore this breed is to be called defective and abnormal in the sense
      of section 11b of the German protection of animals legislation. Poultry fanciers
      reject these findings as incorrect, but accurate scientific examinations that
      bear out this allegation are not available. Preliminary examinations have
      demonstrated that brain and skull anatomy of living animals can be described by
      using non-invasive diagnostic techniques (magnet-resonance-imaging, computerized
      tomography, radiography). The use of this progressive methods enables to
      expressive findings on present stocks of domestic ducks. Many of the test animals
      investigated in preliminary examinations by using magnet-resonance-imaging and
      radiography showed abnormal tissue deposits in the tentorium cerebelli, meningo
      encephalocele, cranial malformations, and variable bone formations in the
      thickened hypodermis of the crest. If crested ducks are mated against each other,
      numerous offspring show malformations of upper beak and cranium, encephalocele,
      as well as craniopagal parasites in form of rudimentary legs.

PMID- 9646408
TI  - [Changes in pharmaceutical market 1996/1997].

PMID- 9646409
TI  - [Relevance of Helicobacter pylori infection in the development of gastric
      tumors].
AB  - Helicobacter pylori plays an important role in the pathogenesis of peptic ulcer
      disease. Besides, epidemiological studies indicate that helicobacter may be
      involved in the development of gastric cancer and MALT-lymphoma by inducing
      gastritis and accumulation of lymph follicles in the gastric mucosa. The
      carcinogenic effect of helicobacter pylori can be explained by various
      pathogenetic factors which are produced by the bacterium itself. Furthermore,
      influences of helicobacter pylori on the vitamin C content of gastric mucosa
      might play a role. Currently, Hp-eradication therapies for the treatment of
      gastric MALT lymphomas are already under investigation in controlled studies.
      Concerning gastric cancer prevention, however, the available data are not
      sufficient to warrant a general recommendation for eradication-therapies of all
      Hp-infected persons. However, further studies must show whether Hp-eradication of
      high-risk subjects, i.e. members of gastric cancer families, young patients with
      chronic-active gastritis or with chronic-atrophic gastritis and intestinal
      metaplasia, are effective in reducing gastric cancer risk.

PMID- 9646410
TI  - [Case report. Rough haired dachshund, male, 13 years].

PMID- 9646411
TI  - [Hazardous material and safety conditions in veterinary practice. 2: Flammable
      liquid, disinfectants and cleansing media, cytostatics, pressurized gases, liquid
      nitrogen, narcotic gases, mailing of diagnostic samples, hazardous waste].
AB  - In the last years the standards for professional handling of hazardous material
      as well as health and safety in the veterinary practice became considerably more
      stringent. This is expressed in various safety regulations, particularly the
      decree of hazardous material and the legislative directives concerning health and
      safety at work. In part 1, a definition based on the law for hazardous material
      was given and the potential risks were mentioned. The correct documentation
      regarding the protection of personal and the purchase, storage, working
      conditions and removal of hazardous material was explained. General rules for the
      handling of hazardous material were described. In part 2, partial emphasis is put
      on the handling of flammable liquids, disinfectants, cytostatica, pressurised
      gases, liquid nitrogen, narcotics, mailing of potentially infectious material and
      safe disposal of hazardous waste. Advice about possible unrecognized hazards and
      references are also given.

PMID- 9646412
TI  - [Ophthalmology quiz. Free pigmented iris cyst in anterior ocular chamber].

PMID- 9646413
TI  - [Feasibility of sonography in the diagnosis of congenital heart diseases in
      dogs].
AB  - In ultrasound examination of the heart it is useful to combine the following
      techniques: echocardiography (in 2D and M-mode) gives information about
      morphology and motion of the heart. By using Doppler echocardiography (black and
      white or preferably colour) it is possible to evaluate bloodstreams and with
      contrast echocardiography shunts in the heart can be demonstrated. In our study
      (1994-1996) the following congenital heart defects were the most common in dogs:
      subaortic stenosis (SAS, 41%), pulmonic stenosis (PS, 19%), patent ductus
      arteriosus (PDA, 11%) and the combination of subaortic stenosis with pulmonic
      stenosis (11%). Echocardiography allows the morphologic evaluation of the primary
      defect in detail, for example the differentiation between aortic valve stenosis
      and subaortic stenosis. However the exact identification of the patent ductus
      arterious and of the morphology in pulmonic stenosis can remain difficult,
      especially in patients showing dyspnoe. In heart sonography quantitative
      measurements are available to graduate the defects, but guidelines for these
      measurements are not yet defined. The demonstration of secondary and combined
      defects, which are important for therapy is easily possible with heart ultrasound
      examination. Secondary insufficiencies are often seen at the mitral valve because
      of primary subaortic stenosis or patent ductus arteriosus and at the tricuspid
      valve because of pulmonic stenosis. For differentiation of combined heart defects
      (SAS with PS; SAS with PDA; PS with atrium septum defect) heart ultrasound is
      extremely valuable.

PMID- 9646414
TI  - [Diabetes mellitus in young dogs and cats. Case reports and a comparison with
      relevant literature].
AB  - Cases of diabetes mellitus in young cats and dogs (younger than five years) are
      described rarely in contrary to reports in older patients (older than eight
      years). Histological alterations of pancreatic islets in young canine and feline
      diabetic patients represent the main issue of this publication together with the
      regenerative capacity of insulin-producing cells in these patients. These
      regenerative phenomenons of differentiated islet cells (replication) or their
      progenitors (neogenesis deriving from stem cells) are detected in young cats and
      dogs in isolated cases whereas they are in general missing in older patients. In
      this publication, own cases are presented together with histopathological as well
      as clinical findings. The cases are discussed with the relevant literature of
      veterinary and human medicine.

PMID- 9646415
TI  - [Idiopathic mucinosis cutis in Chinese Shar pei dogs: epidemiology, clinical
      features, histopathologic findings and treatment].
AB  - Species specific diseases, e.g. idiopathic mucinosis of the Chinese Shar Pei are
      reported by use of 31 clinical cases and 140 biopsy samples. Idiopathic mucinosis
      is one of the most frequent diseases of this increasing breed in Germany, too.
      The disease is diagnosed by use of histologic examination of skin biopsies.
      Therapy is performed by application of corticosteroids and symptomatic treatment.

PMID- 9646416
TI  - [Dog tourism and import: an inquiry in Germany on the extent as well as on the
      spectrum and preference of countries of residence and origin respectively].
AB  - A survey was conducted among practicing veterinarians and at pet clinics in
      Germany in order to estimate the extent of tourism with dogs and import of dogs
      and to determine the range and preference of the foreign countries involved. The
      survey covered the years from 1985 to 1995 and included 5240 dogs, of which 4567
      (87.2%) were born in Germany and 673 (12.8%) were born abroad. Among the latter,
      263 (39.1%) originated from Mediterranean countries and Portugal, 344 (51.1%)
      were born in other European countries and 66 (9.8%) were from non-European
      countries. Of all 5240 dogs surveyed, 2894 (55.2%) had been taken abroad at least
      once between 1985 and 1995. Of these, 2424 (53.1%) were born in Germany, 470
      (69.8%) were born abroad. Of the 2894 dogs taken abroad, 1929 (66.7%) travelled
      to Mediterranean countries or Portugal and 1152 of these had additional travels
      to other countries as well. The spectrum of all countries travelled to was very
      broad, but numerous dogs were taken regularly, repeatedly and exclusively to
      Austria, Switzerland, Italy, Spain or France. Other countries were visited only
      once for the majority of dogs. The analysis of the annual survey data revealed a
      steady increase of dogs along on trips from Germany to other countries, rising
      from 31.1% in 1990 to 40.8% in 1994. In any of these years, always more than 56%
      of these dogs were taken to Mediterranean countries.

PMID- 9646417
TI  - [Eye diseases in dwarf rabbits. 1. Anatomy, investigation procedures, diseases of
      the eyelid, the conjunctiva and the nasolacrimal duct].
AB  - The clinical ophthalmology of dwarf rabbits is reviewed in this continuing
      article. The first part contains the ophthalmological examination scheme and
      anatomical features of the rabbit's eye. Furthermore diseases of the eyelids,
      conjunctiva and of the nasolacrimal duct are described. These are illustrated by
      means of selected photographs.

PMID- 9646418
TI  - [Comparative investigations on inhalation anesthesia with isoflurane (Forene) and
      sevoflurane (SEVOrane) in racing pigeons (Columba livia Gmel., 1789, var.
      domestica) and presentation of a reference anesthesia protocol for birds].
AB  - A conventional inhalation anaesthesia using an isoflurane and sevoflurane-oxygen
      nitrous oxide-mixture was performed in each six domestic pigeons (Columbia livia
      Gmel., 1789, var. domestica). Over a period of 60 minutes routine anaesthetic
      monitoring including reflex score (12 reflexes, cloacal body temperature and
      pulse oximetry) was performed. For anaesthesia maintainance 4.0 +/- 0.3 Vol. %
      sevoflurane compared to 2.0 +/- 0.2 Vol. % isoflurane were used. The induction
      period using sevoflurane was shorter (95 +/- 9 sec) than by using isoflurane (154
      +/- 12 sec). The recovery period was significantly shortened using sevoflurane
      (162 +/- 12 sec) compared to isoflurane with 186 +/- 12 sec. Results show, that
      the use of sevoflurane is indicated especially in patients bearing anaesthesia
      risks, but has a number of advantages, though anaesthetic potency is
      approximately 50% lower than in isoflurane, causing higher costs. Furthermore low
      toxicity of sevoflurane leads to a lower burden for the surgical staff through so
      called "waste gases", which play an important role in avian anaesthesia using a
      head chamber for application. Beside a review on current techniques in avian
      anaesthesia this paper includes a standardised detailed anaesthesia protocol
      description of avian inhalation anaesthesia regarding the technical equipment as
      well as its practice, which allows an exact documentation of the anaesthetic,
      meeting legal requirements, too. The results show that inhalation anaesthesia
      with isoflurane or sevoflurane has to be preferred even in birds when compared to
      ketamine anaesthesia, the future use of which has to be restricted to sedation
      and immobilisation partly due to animal welfare grounds.

PMID- 9646419
TI  - [Therapy of varicocele].

PMID- 9646420
TI  - Pathophysiological effect of varicocele treatment.

PMID- 9646421
TI  - [Effects of varicocele therapy on spermatozoan function].
AB  - Men suffering from varicocele have lower mean sperm counts and "worse" seminal
      parameters than those without a varicocele. Also in those with a varicocele, who
      already fathered a child, the mean sperm count is lower than in other fertile
      men. The observations, however, do not refer specifically to an existing
      varicocele, but are common also in other spermatogenic defects. This holds also
      true for the frequency of tapering forms. Besides the classical parameters of the
      spermatozoa also novel parameters of the extended semen analysis were tested. As
      well in the rate of acrosome-reacting spermatozoa, in the rate of anilinblue
      stained cells, in the number of zona binding-spermatozoa as in the concentration
      of sperm antibodies no differences between men with and men without a varicocele
      were found. The grade of a varicocele does not account for the degree of the
      spermatogenic defect. The progressive damage to the spermatogenesis by an
      persisting varicocele is discussed controversely. It was suggested that an early
      treatment of a varicocele, in particular in the adolescence, might inhibit the
      later insufficiency of sperm production. Correction of a varicocele is followed
      by an improvement of seminal parameters, in particular of sperm motility. In
      controlled studies, however, this effect was also observed in the untreated
      group. This casts some doubt on the causative effect of the varicocele treatment.
      The improvement of seminal parameters is not always accompanied by an increase in
      fertility, although also some functional parameters showed an improvement after
      correction of the varicocele.

PMID- 9646422
TI  - Varicocele: does treatment promote male fertility?

PMID- 9646423
TI  - [Treatment of varicocele in the age of "evidence-based medicine". Medical
      counseling is as successful as interventional treatment (ligation or
      embolization)].
AB  - In the age of "evidence-based medicine" the results of controlled clinical trials
      form the basis of therapeutic decisions. Until recently, interventional treatment
      has been the routine therapy for an infertile man with varicocele. However,
      recent controlled studies have shown that intensive counselling of the infertile
      couples results in as many pregnancies as ligation of embolization of the
      spermatic vein. Therefore, the traditional treatment regimen for varicocele
      should be reconsidered and the pathophysiology of the varicocele should be
      elucidated to provide a basis for rational treatment.

PMID- 9646424
TI  - [A critical analysis of studies of varicocele therapy from the biostatistics
      viewpoint].
AB  - Since approximately 45 years subfertile patients with varicocele are treated with
      different techniques of a varicocelectomy if there are no (other) causes of
      infertility. In the meantime, a varicocelectomy is being applied prophylactically
      in adolescents, too. In this article, there should be investigated whether the
      conducted clinical trials provide evidence of the efficacy of a varicocelectomy.
      Due to the fact that there are only a few valuable trials concerning the therapy
      of varicocele, the meta-analysis is mainly a critical analysis of the considered
      biostatistical methods. It comes to the conclusion that there is no clinical
      evidence for efficacy as well as against, and this conclusion is valid for the
      treatment as well as for the prophylaxis of male factor infertility. To achieve
      evidence, intensification of cooperation in multicenter study groups is necessary
      and methodical quality of the clinical trials on varicocelectomy should be
      improved.

PMID- 9646425
TI  - [Therapy of varicocele. Attempt at assessment of current status].

PMID- 9646426
TI  - [Mycophenolate mofetil (MMF) for prevention of kidney transplant rejection. A new
      immunosuppressive agent. International Mycophenolate Mofetil Study Group].
AB  - 1493 patients were enrolled in 55 centers in Europe, Canada, Australia and the
      USA comparing the efficacy of mycophenolate mofetil (MMF) in daily doses of 2 and
      3 g with placebo/azathioprine (PLA/AZA) for the prevention of acute rejection in
      renal transplant patients. Acute rejections and graft loss and death at 1 year
      were measured per trial and these data were combined and analyzed in a pooled
      fashion. The three pooled treatment groups were well balanced regarding
      demographic characteristics and cause of renal failure leading to
      transplantation. At one year the graft survival rate was 90.4% and 89.2% in the
      MMF 2 g and 3 g groups compared with 87.6% in the PLA/AZA-group. MMF 2 and 3 g
      were significantly better than PLA/AZA in reducing biopsy proven rejection at one
      year: 40.8% placebo/aza vs. 19.8% in the MMF 2 g group and 16.5% in the MMF 3 g
      group.

PMID- 9646427
TI  - [Provocation of corpus cavernosum EMG signals as a parameter in diagnosis of
      erectile dysfunction].
AB  - Parameters of CC-EMG able to distingiush between healthy controls and men with
      erectile dysfunction of different etiology in the individual case are currently
      unknown. Groups of healthy volunteers and men with erectile dysfunction however
      show significant differences in provocability of slow cavernous electric
      activity, i.e. if so called "typical single potentials" (tSP) can be recorded
      already under resting conditions, or only with provocation, or if any activity is
      missing. In men, who showed tSP already under resting conditions, a significantly
      higher extent of provoked activity could be assessed as in those, who showed tSP
      only after provocation. This applies to the number as well as for the extent of
      the responses to the 3 stimuli valsalva-manoeuvre, arousal and hyperventilation.
      Patients, who had shown tSP already under resting conditions, were similar to the
      controls, from whom those, who showed tSP exclusively with provocation differed
      significantly. Further research will have to prove, if the parameter
      "provocability" together with the parameter "extent of the provoked cavernous
      electric activity" might be able to to lead to a better distinction of healthy
      and pathological situations which would be a precondition for the introduction of
      the method into clinical use.

PMID- 9646428
TI  - [Lymphocyte transformation test (LTT) as a model for evaluating cytokine-induced
      immunomodulation in renal cell carcinoma].
AB  - We investigated the immunomodulatory capacity of cytokines produced by renal cell
      carcinoma in vitro by analyzing their effects on mitogen-induced T-lymphocyte
      blast cell transformation. All of the tested 70 cell cultures, derived from 70
      tumor areas in 33 patients, had immunomodulatory capacity. In addition to
      suppression in the lymphocyte transformation test (max. 44/70; 63%) there was
      also superinduction (max. 37/70; 53%). We found no significant correlation with
      the stage and grade of primary tumors. However, the suppression of mitogen
      induced T-lymphocyte blast cell transformation was significant in multifocal
      tumors (0.08% TCM, P < 0.001) and non-significant in metastatic tumors. The
      production of the assayed cytokines IL-6, IL-10, IL-11, and TGF beta 1 was
      variable and there was no significant correlation to the immunomodulatory
      capacity of the tumors.

PMID- 9646429
TI  - [Prognostic relevance of vena cava thrombosis in renal cell carcinoma].
AB  - The independent prognostic value of neoplastic extension of renal cell cancer
      (RCC) into the vena cava inferior has been the subject of several investigations
      reported to date. However, the use of vena cava thrombosis as an independent
      prognosticator of a patient's long-term survival is still debated. We have
      therefore correlated the clinical course of 53 patients with RCC and vena cava
      thrombosis with a control group consisting of 47 patients with renal cell tumors
      without vena cava thrombosis (follow-up: 1-154 months). The median long-term
      survival of patients with and without vena cava thrombosis was 32 and 35 months,
      respectively. Neither the propagation of the tumor into the vena cava (P = 0.391)
      nor the cranial extension of the thrombosis (P = 0.158)--even in case of
      propagation into the right atrium--could be identified as parameters of any
      prognostic value during univariate or multivariate statistical analysis.

PMID- 9646430
TI  - [Collagen metabolism in induratio penis plastica (IPP)].
AB  - The exact pathogenesis of Peyronie's Disease (PD) is still unknown.
      Histopathological investigations suggest, that the metabolism of the collogenious
      tissue plays an important role. Therefore, we started a prospective study in
      order to evaluate the metabolic situation of 11 patients with PD and 11 healthy
      controls. We measured biochemical parameters of penile and venous blood, which
      correspond to the collagen metabolism (procollagen III [P III P], PMN-elastase
      [PMN-E], fibronectin [FN], fibronectinreceptor [FN-R] und alpha-1-proteinase
      inhibitor [alpha-1-PI]). There was no difference in PMN-E, P III P, FN and FN-R
      in all samples. There was no difference in penile and venous blood as well. But
      we found out a highly significant lower concentration of alpha-1-PI in patients
      with PD (158,55 mg/dl) than in controls (214,82 mg/ dl). A deficiency of alpha-1
      PI can lead to a higher activity of serum proteases, such as PMN-E. This can
      result in a change in collagen metabolism by an increased synthesis of collagen
      type III, that is found in PD. This general pathophysiologic factor may be
      competed by an additional local alteration of the tissue.

PMID- 9646431
TI  - [Paraneoplastic syndromes].

PMID- 9646432
TI  - [Kidney parenchyma carcinoma--diagnosis. German Society of Urology].

PMID- 9646433
TI  - [Para-spinal regional anesthesia and prevention of
      thromboembolism/anticoagulation. Recommendations of the German Society of
      Anesthesiology and Intensive Care Medicine, October 1997].

PMID- 9646434
TI  - Modulation of T cell and monocyte function in the spleen following infection of
      pigs with African swine fever virus.
AB  - Infection of pigs with many strains of African Swine Fever Virus (ASFV) has been
      shown to cause a loss or marked decrease in the ability of splenocytes to respond
      to mitogens. These observations have been extended by cell fractionation and
      reconstitution experiments to show that the mitogen stimulated proliferative
      capacity of both the CD4+ and CD8+ T cells is affected. Similarly, monocytes
      which are directly infectable by virus, are functionally defective as antigen
      presenting cells when added to mitogen stimulated normal T cells. Interestingly,
      the same T cells which respond poorly in mitogenic assays can be activated by
      stimulation through the CD3 receptor. In contrast to the defective mitogenic
      response of T cells, B cell function, as assessed by stimulation through the CD40
      ligand in vitro remains intact. There is no evidence for apoptosis in either the
      T cells or the B cells recovered from the spleens of ASFV infected animals 1-5
      days following infection. Although the number of leucocytes which can be
      recovered from the infected spleen decreases rapidly with progression of the
      disease, the proportion of the different cell phenotypes remains constant. Thus
      decreased activity of lymphocytes in lymphoid tissue from ASFV infected animals
      appears to be directly attributable to infection of the monocytes.

PMID- 9646435
TI  - Tumor necrosis factor and interferon activity in the circulation of calves after
      repeated injection of low doses of lipopolysaccharide.
AB  - The effect of two intravenous (i.v.) injections of low doses of
      lipopolysaccharide (LPS)(0.1 microgram/kg of body weight) administered at 7-day
      intervals on the systemic release of tumor necrosis factor (TNF) and interferon
      (IFN), on the rectal temperature, breathing and heart rate, and on packed cell
      volume (PCV), plasma glucose concentration, white blood cell (WBC) counts in 3
      week-old calves, was estimated. The first injection of LPS caused a significant
      increase in breathing and heart rate, rectal temperature, prolonged hypoglycemia
      and leukopenia, but no significant changes in PCV were observed. TNF and IFN
      activity peaked at 2 h after LPS injection and disappeared from circulation by 4
      h and 5 h, respectively. After the second injection of LPS, the reaction of
      calves was similar to that observed after the first injection, however, the
      breathing rate and TNF systemic production were significantly reduced. The
      results obtained indicate that a low dose of LPS leads to the development of
      'late' tolerance manifested by hyporeactivity to TNF production but with
      maintained responsivity to IFN production, pyrogenic, hypoglycemic and leukemic
      response to the second injection of LPS. In conclusion, these results demonstrate
      that the tolerance response is not universal to all hematologic and immunologic
      parameters, and that the response needs to be evaluated with respect to the
      specific variable.

PMID- 9646436
TI  - Compensation of preliminary blood phagocyte immaturity in the newborn calf.
AB  - To estimate the functional maturity of the phagocytic defence in neonatal calves,
      we analyzed the characteristics of blood phagocytes from calves (n = 10) 1 h post
      partum (p.p.) and 4 h p.p. At 1 h p.p., all calves were colostrum-deprived, while
      5 calves had received colostrum before the 4 h p.p. sampling. The results were
      compared to those obtained from 3-9-week-old calves (n = 10). Phagocytic and
      oxidative burst activity of polymorphonuclear leukocytes (PMNL) and monocytes
      were determined in whole blood and separately analyzed by flow cytometry. In
      neonates prior to colostrum ingestion (1 h p.p.), phagocytic activity of PMNL
      against non-preopsonized E. coli was lower when compared to PMNL of 3-9-week-old
      calves. Opsonization of bacteria with pooled plasma from adult animals only
      partially restituted this lower PMNL phagocytic activity, indicating that humoral
      as well as cellular aspects of PMNL phagocytosis are altered in neonatal calves.
      In contrast to PMNL, monocytes of neonates exhibited an enhanced phagocytic
      activity. The oxidative burst activity of PMNL, as well as of monocytes was
      higher in newborn calves. During the first 4 h of life, the activities of blood
      phagocytes changed. Colostrum ingestion was accompanied by an increase in the
      percentage of phagocytizing PMNL and monocytes. This increase was absent in
      colostrum-deprived calves. In contrast, the oxidative burst activity of
      phagocytes decreased with age. In monocytes, the decrease of oxidative burst
      activity was only observed in colostrum-fed calves. In conclusion, some blood
      phagocyte functions in calves were found to be immature at birth, but these
      functions are presumably compensated by high absolute PMNL numbers and by other
      the more active mechanisms.

PMID- 9646437
TI  - Comparative morphofunctional study of dispersed mature canine cutaneous mast
      cells and BR cells, a poorly differentiated mast cell line from a dog
      subcutaneous mastocytoma.
AB  - The dog mastocytoma BR cell line provides us with a permanent source of canine
      mast cells, allowing a characterization of secretory mediators that exert
      important effects in canine allergic and nonallergic diseases and in
      physiological processes. We studied the ultrastructural characteristics and
      histamine releasing activity after immunological and non-immunological stimuli of
      the dog mastocytoma BR cell line, and compared the cell line to normal skin mast
      cells enzymatically isolated from healthy dogs. The histamine content of BR cells
      was 0.04 +/- 0.002 pg/cell, approximately 100-fold less than that found in canine
      skin mast cells. Non-immunologic stimuli induced similar concentration-dependent
      histamine release from skin mast cells and BR cells: 29.3 +/- 0.9% vs. 12.7 +/-
      0.7% (calcium ionophore A23187), 23.3 +/- 0.7% vs. 18.8 +/- 0.7% (substance P)
      and 12.5 +/- 0.3% vs. 12.1 +/- 0.9% (compound 48/80), respectively. Immunologic
      stimulation, however, was only effective on canine skin mast cells, causing 30.9
      +/- 1.7%, 27.7 +/- 0.6% and 12.2 +/- 0.9% histamine release in response to anti
      canine IgE, concanavalin A, and antigen Asc S 1, respectively. The absence of
      functional IgE receptors in BR cells was confirmed by the lack of response to
      anti-IgE and antigen Asc S 1 following passive sensitization with dog atopic
      serum and dog antigen sensitized serum. We conclude that BR cells are able to
      release histamine after non-immunologic stimulation in a similar manner to canine
      skin mast cells, but that there are morphological and functional differences
      possibly due to different states of maturity or differentiation. For this reason
      the study of the highly homogeneous BR cells could offer insights into dog mast
      cell biology in contexts where freshly isolated cells cannot be used because of
      low purity and recovery.

PMID- 9646438
TI  - CD4, CD8 and TCR defined T-cell subsets in thymus and spleen of 2- and 7-week old
      commercial broiler chickens.
AB  - To better understand immune development and function in meat-type chickens
      (broilers), the proportions of T-cells expressing CD4, CD8, and T-cell receptors
      (TCR) in the thymus and spleen were determined by three-color fluorescence and
      flow cytometry in 2- and 7-week old broilers raised in commercial growing
      conditions. Broiler thymocytes consisted of single-(CD4+CD8- and CD4-CD8+) and
      double-(CD4+CD8+) positive subpopulations. Within these CD4+ and/or CD8+
      thymocyte populations, all types of TCR (y delta, V beta 1 alpha beta, and V beta
      2 alpha beta) could be identified. In the thymus, percentages of CD4+CD8- cells
      increased, CD4-CD8+ cells remained unchanged, and CD4+CD8+ cells decreased
      between 2 and 7 weeks of age. In the spleen, in addition to single-positive
      lymphocytes, double-positive populations were identified, expressing either y
      delta or alpha beta TCR. The percentage of CD4+CD8- splenocytes decreased, and
      the percentages of both CD4-CD8+ and CD4+CD8+ splenocytes increased between 2 and
      7 weeks of age. Age-associated shifts in TCR usage (the proportion of cells
      expressing a certain type of TCR) were observed in the single-positive, but not
      in the double-positive, T-cell populations of both thymus and spleen. This
      multiparameter cell population analysis in broilers demonstrates thymic and
      splenic T-cell subsets similar to those previously described in layers.
      Differences in the proportions among T-cell subsets between 2- and 7-week old
      broilers likely reflect a more competent immune system in the older birds.

PMID- 9646439
TI  - In vitro effects of the extracellular protein of Renibacterium salmoninarum on
      phagocyte function in brook trout (Salvelinus fontinalis).
AB  - Renibacterium salmoninarum is a facultative intracellular pathogen often found in
      host phagocytes where it appears to successfully avoid the host fish's
      immunological defenses. The objective of this investigation was to determine if
      soluble extracellular protein (ECP) produced by R. salmoninarum may contribute to
      the immunomodulation in bacterial kidney disease (BKD) via inhibition of
      phagocyte respiratory burst and/or phagocytosis mechanisms. Splenic cells from
      adult brook trout (Salvelinus fontinalis) were incubated with two different
      concentrations of ECP (0.1 mg/ml and 1.0 mg/ml) and viable R. salmoninarum.
      Splenic cell cultures were evaluated for respiratory burst activity via flow
      cytometry with the dichlorofluorescin diacetate (DCF-DA) assay and for
      phagocytosis via light microscopic assessment of microsphere engulfment.
      Respiratory burst activity was significantly inhibited in all treatment groups as
      compared to untreated fish, while no differences were noted in phagocytic
      activity.

PMID- 9646440
TI  - In vitro interaction of viral haemorrhagic septicaemia virus and leukocytes from
      trout (Oncorhynchus mykiss) and turbot (Scophthalmus maximus).
AB  - Viral haemorrhagic septicaemia virus (VHSV), a well known salmonids pathogen, has
      also been reported to be pathogenic for turbot (Scophthalmus maximus). In the
      present work, the replication of VHSV was studied in vitro in turbot head kidney
      macrophages and blood leukocytes. VHSV was able to infect both primary cultures
      and viral titer increased with time, either inside the cells or in the
      supernatant. However, no cytopathic effect was observed during the experiments
      and the titers were always lower than those obtained in the fish cell lines. The
      number of trout and turbot macrophages after several days of in vitro infection
      with VHSV was compared with uninfected controls by viable cell count but no
      significant differences were observed. The number of cells supporting viral
      replication evaluated by immunofluorescence in trout and turbot was low (8 and
      1.7%, respectively). Respiratory burst activity of head kidney macrophages was
      assayed at different days post-infection, but no significant differences were
      found between the control and the infected cultures neither in trout nor turbot.

PMID- 9646441
TI  - Reactivation of latent bovine herpesvirus 1 in cattle seronegative to
      glycoproteins gB and gE.
AB  - Six heifers were vaccinated intranasally with the live bovine herpesvirus 1
      (BHV1) temperature-sensitive (ts) vaccine strain RBL106 within 3 weeks of birth.
      These calves most likely still had maternal antibodies against BHV1. Thereafter,
      these heifers were vaccinated several times with an experimental BHV1
      glycoprotein-D (gD) subunit vaccine. At the age of 3 years these 6 heifers were
      seronegative in the BHV1 gB and gE blocking ELISAs, but had neutralizing
      antibodies against BHV1, probably induced by the vaccinations with the gD subunit
      vaccine. Five of these 6 heifers excreted BHV1 after treatment with
      dexamethasone. Restriction enzyme analysis of the genome of the excreted viruses
      revealed that all 5 isolates had a BHV1.1 genotype and that isolates of 3 heifers
      were not obviously different from the ts-vaccine strain. The restriction enzyme
      fragment pattern of the isolate of 1 heifer was clearly different from the
      pattern of the ts-vaccine strain. It is concluded that cattle can be seronegative
      against BHV1 gB and gE but can still carry BHV1 in a latent form. This finding
      strongly suggests that there are completely BHV1 seronegative cattle that are
      latently infected with BHV1. The impact of this finding on BHV1 eradication
      programmes is discussed.

PMID- 9646442
TI  - Aujeszky's disease (pseudorabies) virus detection in cerebrospinal fluid in
      experimentally infected pigs.
AB  - The presence of Aujeszky's disease virus in cerebrospinal fluid of experimentally
      infected pigs was studied using the techniques of virus isolation and PCR. Pigs,
      some of which were previously vaccinated against Aujeszky's disease, were
      inoculated with different doses of the Aujeszky's disease NIA-3 strain. At the
      time of death or sacrifice, a sample of cerebrospinal fluid was taken and tested
      for the presence of virus using the mentioned techniques. Virus was isolated only
      from one sample, while it was detected by PCR in most of them. The higher
      sensitivity of the PCR technique and the possible presence of antiviral
      antibodies in the cerebrospinal fluid are reasons that can be argued to explain
      this fact. By PCR, the virus was detected more efficiently when digested
      cerebrospinal fluid cells were used as DNA source than when using whole
      cerebrospinal fluid, suggesting that the virus could be cell-associated.
      Aujeszky's disease virus could not be detected by PCR in pigs which survived the
      acute phase of the infection and were euthanased at 8 weeks post-inoculation,
      when they were latently infected. This indicated that the cerebrospinal fluid is
      not an adequate sample for the diagnosis of latency. Since Aujeszky's disease
      virus was detected from most of the tested samples, we believe that this could be
      an adequate procedure for the quick diagnosis of Aujeszky's disease.

PMID- 9646443
TI  - Suppression of pseudorabies virus replication by a mutant form of immediate-early
      protein IE180 repressing the viral gene transcription.
AB  - A mutant form of the immediate-early (IE) protein IE180 of pseudorabies virus
      (PRV), dIN454-C1081 is a strong repressor of the PRV IE gene promoter. In order
      to assess the antiviral potential of the IE180 mutant, HeLa cells were
      transformed with the mutant gene and then infected with PRV and herpes simplex
      virus type 1 (HSV-1). The transformed cell lines showed marked resistance to PRV
      infection, but were susceptible to infection with HSV-1, indicating that the
      IE180 mutant expressed in the stable cell line specifically inhibited PRV growth.
      In those cells infected with PRV, transcription of the PRV IE gene was repressed.
      In addition, the IE180 mutant exhibited a dominant-negative property in transient
      expression assay. The present results indicate that the resistance of the cells
      to PRV infection was due to repression of the IE gene transcription by the IE 180
      mutant.

PMID- 9646444
TI  - Detection of canine oral papillomavirus-DNA in canine oral squamous cell
      carcinomas and p53 overexpressing skin papillomas of the dog using the polymerase
      chain reaction and non-radioactive in situ hybridization.
AB  - Nineteen cutaneous and mucocutaneous papillomas, as well as 29 oral and 25 non
      oral squamous cell carcinomas of dogs were analyzed immunohistologically for the
      presence of papillomavirus (PV)-antigens. Canine oral papillomavirus (COPV)-DNA
      was detected in formalin-fixed, paraffin-embedded tissues by polymerase chain
      reaction (PCR) and non-radioactive in situ hybridization (ISH). Furthermore, the
      expression of the tumor suppressor protein p53 was investigated. PV-antigens were
      detectable in more than 50% of the oral and cutaneous papillomas, while no PV
      antigens could be demonstrated in venereal papillomas. One squamous cell
      carcinoma was PV-antigen positive. Only two cutaneous papillomas of the head
      showed a strong p53-specific immunostaining, while overexpressed p53 was
      detectable in approximately 35% of all squamous cell carcinomas. It was possible
      to amplify fragments of the E6, E7 and L1 gene by polymerase chain reaction (PCR)
      from five of eight oral and from five of eight cutaneous papillomas as well as
      from three oral squamous cell carcinomas. Nine of 10 papillomas showed a strong
      nucleus-associated hybridization signal typical for COPV-DNA. In three squamous
      cell carcinomas COPV-DNA was located in nests of the epithelial tumor cells
      surrounding 'horn pearls' or disseminated in the carcinoma tissue. These
      observations support the view that COPV may also induce non-oral papillomas in
      the dog and confirm the opinion that a progression of viral papillomas into
      carcinomas in dogs may occur.

PMID- 9646446
TI  - In vivo functions of the auxiliary genes and regulatory elements of feline
      immunodeficiency virus.
AB  - Feline immunodeficiency virus (FIV) is a widespread lentivirus of domestic cats
      that causes an acquired immunodeficiency syndrome (AIDS)-like disease similar to
      human AIDS caused by human immunodeficiency virus. FIV has a complex genome
      structure including structural, enzymatic and auxiliary genes and regulatory
      elements. In this article, we review the in vivo roles of some of these FIV
      auxiliary genes and regulatory elements, especially focusing on the dUTPase, vif,
      and ORF-A genes and AP-1 binding site in the enhancer region of the long terminal
      repeat, by comparison with those of other non-primate lentiviruses. These genes
      and elements are considered to be important for viral replication, immunological
      response and pathogenesis in cats.

PMID- 9646445
TI  - Entry of African swine fever virus into Vero cells and uncoating.
AB  - African swine fever virus (ASFV) enters Vero cells by adsorptive endocytosis
      [Valdeira, M.L., Geraldes, A., 1985. Morphological study on the entry of African
      swine fever virus into cells, Biol Cell. 55, 35-40]. Electron microscopy of a
      lysosomotropic drug-controlled penetration indicated that this step takes place
      in the endosomes, after fusion between the viral envelope and the limiting
      membrane of the endosome. Inhibition studies with colcemid, cytochalasin B,
      sodium azide, dinitrophenol, lysosomotropic weak bases, and the ionophore
      monensin, showed that the virus uptake is largely independent of cytoskeletal and
      lysosomal function, but dependent on oxidative phosphorylation. Some protease
      inhibitors inhibited viral replication at an early step, indicating that the
      initiation of infection depends on a viral proteolytic cleavage.

PMID- 9646447
TI  - Development and evaluation of a novel antigen capture assay for the detection of
      classical swine fever virus antigens.
AB  - An antigen-capture enzyme immunoassay (EIA) was developed to detect classical
      swine fever virus (CSFV) antigen directly from 10% w/v tissue suspension. The
      assay, based on the sandwich principle, uses a biotinylated monoclonal antibody
      bound to streptavidin-coated microplates as the capture system and a swine anti
      CSFV antibody and rabbit anti-swine HRPO-conjugate as the detector system. The
      antigen-capture EIA was compared with conventional virus isolation and polymerase
      chain reaction (PCR) for detection of CSFV in tissues. The ability of the antigen
      capture EIA to discriminate classical swine fever (CSF) from bovine viral
      diarrhea and African swine fever viruses was also tested. The assay was shown to
      detect 21 different strains of CSFV and was unreactive with tissues from
      uninfected animals. Signal to noise (S/N) ratios were calculated from the EIA
      absorbance values. Readings from samples positive by virus isolation (n = 47)
      averaged a S/N ratio of 5.34. In contrast, samples negative by virus isolation (n
      = 96) demonstrated a mean S/N ratio of 0.16. At S/N cut-off value of 1.0, all
      samples that yield virus isolation and PCR negative result were negative in the
      antigen-capture EIA. Compared with virus propagation in tissue culture using PK15
      cells (followed by indirect peroxidase assay detection) and PCR, the EIA had a
      specificity of 98.7% and a sensitivity of 91.4%. The EIA is simple, can be
      performed in 4 h and lends itself to automation for screening of tissues sample
      from pigs suspected of CSFV infection.

PMID- 9646448
TI  - Blocking ELISA's for the distinction between antibodies against European and
      American strains of porcine reproductive and respiratory syndrome virus.
AB  - A double blocking ELISA was developed in order to satisfy the need for large
      scale serological screening for PRRS and simultaneous distinction between
      infection with European and American strains of PRRSV in pig herds. The
      Immunoperoxidase monolayer assay (IPMA) and the double blocking ELISA enabled
      distinction on serological basis between infection with European and American
      strains of PRRSV. The distinction was possible from about day 7 after infection
      of pigs with PRRSV. The double blocking ELISA enabled the distinction at later
      stages of infection compared to the IPMA, irrespective of the strain involved.

PMID- 9646449
TI  - A competitive ELISA for the specific diagnosis of contagious bovine
      pleuropneumonia (CBPP).
AB  - A competitive ELISA, using a specific monoclonal antibody, was designed to detect
      antibodies to Mycoplasma mycoides subsp. mycoides SC, the agent of contagious
      bovine pleuropneumonia. One monoclonal antibody was found suitable for such a
      test, '117/5', it does not cross-react with any of the other mycoplasma species
      tested, furthermore, its binding is inhibited by positive sera. The cutoff, 50%
      of inhibition, was determined using a set of negative sera from CBPP-free areas.
      The sensitivity was controlled with sera from artificially infected animals as
      well as from sera from areas where CBPP is enzootic. In both cases, cELISA
      compared favorably with CFT. The precocity of detection was similar but cELISA
      detected more positives and the positive titers seemed to persist longer than in
      the case of CFT. Lysis of the antigen used to coat the ELISA plates reduced the
      variability of fixation and improved the repeatability of the test. A field
      evaluation is now in progress which will determine the true sensitivity and
      specificity of the test and also check if antibodies are detected after
      vaccination.

PMID- 9646450
TI  - Humoral immune responses to Mycoplasma hyopneumoniae in sows and offspring
      following an outbreak of mycoplasmosis.
AB  - Previously healthy sows, seropositive to Mycoplasma hyopneumoniae, developed
      clinical signs of mycoplasmosis, as well as increasing amounts of antibodies to
      M. hyopneumoniae during an outbreak of the disease in a herd. During the early
      phase of the outbreak, young piglets (2 weeks) with maternal antibodies remained
      healthy while older seronegative piglets (4-7 weeks) developed the disease. The
      duration of the maternal antibodies to M. hyopneumoniae varied between litters
      and was related to the amount of antibodies in the serum of the dam. In sows, the
      level of serum antibodies decreased continuously from 4 weeks ante partum to
      partus, and the level of antibodies in the whey of colostrum was comparable to
      that in serum 4 weeks ante partum. After loss of maternal antibodies to M.
      hyopneumoniae, seropositive animals were not found among piglets younger than 9
      weeks. Therefore peripheral blood mononuclear cells (PBMC) were collected from
      various age categories of piglets in order to measure the ability to produce
      antibodies to M. hyopneumoniae in vitro. PBMC obtained from piglets aged 1 and 3
      weeks produced few antibodies to M. hyopneumoniae. Significantly higher levels of
      antibodies to M. hyopneumoniae were produced by PBMC obtained from pigs aged 5-9
      weeks. Thus, the ability of PBMC to produce antibodies to M. hyopneumoniae in
      vitro seemed to be age-dependent.

PMID- 9646451
TI  - Comparison of serological tests for detection of Mycoplasma gallisepticum
      antibodies in eggs and chicks hatched from experimentally infected hens.
AB  - Specific pathogen free hens and males were experimentally infected with
      Mycoplasma gallisepticum. Eggs were then collected, and a part was incubated and
      set for hatching. Mycoplasma cultures were performed on infected adults and
      antibodies to MG were analysed by use of slide agglutination (SA) test and
      commercial ELISA tests on adults and chicks sera and on yolks from non incubated
      eggs. Both ELISA tests could detect antibodies in yolks from non incubated eggs
      laid three weeks after infection. SA and the three ELISA tests revealed positive
      sera in chicks hatched from eggs laid as soon as one week after infection.

PMID- 9646452
TI  - Effect of Bacillus subtilis spore administration on activation of macrophages and
      natural killer cells in mice.
AB  - The effect of Bacillus subtilis (strain A102) spores on the activation of murine
      macrophages and natural killer cells (NK) was examined. The macrophage activity
      and NK activity were enhanced by oral administration of A102 spores, and slightly
      enhanced by oral administration of culture supernatant. There was no difference
      in the results of macrophage activity and NK activity using other live or dead
      spores. The NK activity and macrophage activity were increased with increments of
      concentration up to 0.1 g per mouse, and both activities were decreased at
      concentration of more than 0.15 g per mouse. The NK activity was increased 1 and
      2 days after oral administration of A102 spores, and the activity level 2 days
      after administration was about 3-fold higher than the level prior to treatment.
      Macrophage activity was also increased from 1 to 3 days after oral administration
      of A102 spores, and the activity level 3 days after administration was about 3
      fold higher than the level prior to treatment. The induction of interferons at 1
      day after oral administration in mouse serum was 5-fold higher than that in
      controls. These findings indicate that oral administration of A102 gave rise to
      the induction of interferons, and it is likely that macrophages and NK cells were
      activated by interferons.

PMID- 9646453
TI  - An avian pathogenic Escherichia coli strain produces a hemolysin, the expression
      of which is dependent on cyclic AMP receptor protein gene function.
AB  - An avian pathogenic Escherichia coli strain M1000 showed a clear zone of
      erythrocyte lysis on sheep blood agar plates. The hemolytic activity was not
      detected in the culture supernatant nor was any DNA sequence homologous to the E.
      coli alpha-hemolysin gene detected in the chromosome or plasmid DNA of the
      strain, indicating that the observed hemolysis was different from alpha-type. To
      identify the genetic determinant responsible for the hemolysis, we performed
      random Tn5 insertional mutagenesis and obtained one mutant, named M5005, that
      totally lacked the hemolytic activity. Cloning and nucleotide sequencing of the
      region flanking the transposon insertion site in the M5005 chromosome revealed
      that the transposon was inserted within an open reading frame of the cyclic AMP
      receptor protein (CRP) gene, which is involved in one of the global regulatory
      networks of gene expression in E. coli. Nucleotide sequence analysis of the
      intact crp gene of the strain M1000 showed that the CRP protein of M1000 is 99%
      identical to that of K-12. Introduction of the intact crp gene on a low copy
      plasmid into the mutant M5005 restored the hemolytic phenotype, confirming that
      the mutation site in M5005 was in the crp gene. CRP plays a central role in
      catabolite repression, the phenomenon by which the synthesis of many enzymes
      required to metabolize various sugars is repressed in the presence of glucose.
      When the hemolytic activity of E. coli M1000 grown in the presence of glucose was
      examined, the hemolysis was totally impaired. These results indicate that the
      avian pathogenic E. coli strain M1000 produces a hemolysin the expression of
      which is dependent on crp gene function.

PMID- 9646454
TI  - Isolation and molecular analysis of colonising and non-colonising strains of
      Campylobacter jejuni and Campylobacter coli following experimental infection of
      young chickens.
AB  - Fourteen-day-old chickens were inoculated with selected Campylobacter coli and C.
      jejuni strains. C. jejuni strains were of two subgroups based on a polymorphism
      detected using a DNA probe and represented the profiles typical for the majority
      of strains of either chicken or human origin. All C. coli strains previously
      isolated from humans colonised chickens, whereas from 4/7 C. jejuni strains of
      human origin, failed to colonise. Of 12 Campylobacter strains of chicken origin,
      10 established a persistent colonisation in the chickens, and 2 strains colonised
      poorly or not at all. Four strains that failed to colonise chickens were each
      inoculated into groups of five birds. Three strains again did not colonise any of
      the chickens and the fourth strain colonised four out of the five chickens, but
      was poorly excreted. When infected chickens were placed in the same enclosure to
      facilitate interchange of strains, C. jejuni strain 331 was found to be dominant
      and colonised all 12 chickens by 21 days, displacing all other strains. C. jejuni
      strain 331, was then inoculated into groups of five birds with previously
      established colonisation by C. jejuni and C. coli strains. Strain 331 was able to
      replace the C. jejuni strain in all five birds but established co-colonisation
      with C. coli strain. Naturally occurring co-colonisation by two C. jejuni strains
      was detected in one chicken out of 200 tested. There was no obvious correlation
      between the type of DNA polymorphism in strains of chicken origin and their
      ability to colonise chickens.

PMID- 9646455
TI  - Molecular epidemiology of Mycobacterium bovis isolates from South America.
AB  - One hundred seventy-eight isolates of Mycobacterium bovis were subjected to DNA
      restriction fragment length polymorphism (RFLP) analysis, using the direct repeat
      element (DR) and the polymorphic GC-rich repeat sequence (PGRS) as probes. By
      combining the patterns generated by the two repeat DNA elements, 93 different
      patterns were observed. One hundred-one isolates were grouped in clusters, which
      include 25 different clusters. One pattern was the most frequently observed,
      clustering 18.5% of isolates. It was only found in the Center and northeast
      regions of Argentina and in one isolate from Paraguay. The isolates from Brazil
      analyzed here presented exclusive patterns (only found in a particular region).
      The number of exclusive patterns was high in all argentine regions: northeast
      78%, center 81%, and Buenos Aires 81%.

PMID- 9646456
TI  - Serological and bacteriological observations on experimental infection with
      Salmonella hadar in chickens.
AB  - Over the past 3 years the frequency of Salmonella hadar infections has increased
      in Belgium in both poultry and humans. Therefore, the course of infection with S.
      hadar in poultry was investigated. One day-old and 4 week-old specific pathogen
      free chickens were orally infected with one of two S. hadar strains, SH1 or SH2.
      Mortality was 6% (SH1) and 17% (SH2) in birds infected at 1 day-old. Chickens
      infected at 1 day-old with SH2 showed a mild diarrhoea. The S. hadar faecal
      excretion in birds infected at 1 day-old remained high throughout the experiment
      until 12 weeks post-inoculation (pi). Faecal excretion was lower in older birds.
      Antibodies to S. hadar were observed from 2 weeks pi (SH2, infected at 1 day-old)
      or 4 weeks pi (SH1, both groups; SH2, chickens infected at 4 weeks of age). The
      percentage of chickens with antibodies was higher after infection at 1 day-old
      than after infection at 4 weeks of age. In a second experiment 1 day-old chicks
      were infected with SH1 and autopsied at regular intervals until 42 days pi. SH1
      was isolated from the caeca from 3 h pi onwards and from the liver and spleen
      from 18 h until 14 days pi. Serous typhlitis and omphalitis were the main
      lesions. The number of macrophages in the lamina propria of the caecal tonsils
      was slightly increased from 18 h until 2 weeks pi. In the liver, inflammation was
      observed in the portal triads and in the sinusoids. This study indicates that
      infections with S. hadar lead to intense colonisation of the gut and extensive
      faecal shedding. It may also cause invasive infections in 1 day-old chickens.

PMID- 9646457
TI  - Nucleotide sequence homology to bovine viral diarrhea virus 2 (BVDV 2) in the 5'
      untranslated region of BVDVs from cattle with mucosal disease or persistent
      infection in Japan.
AB  - Cytopathogenic and non-cytopathogenic bovine viral diarrhea viruses (BVDVs) were
      isolated from cattle with mucosal disease or persistent infection in Japan. These
      isolates were compared for antigenic properties by cross-neutralization tests
      with Japanese reference strains of BVDV belonging to classical type 1.
      Significantly low cross-reactivity to reference strains was noted, indicating the
      viruses to possibly represent a new serotype in Japan. Thus, to determine the
      genotype of the isolates, nucleotide sequences of the 5' untranslated region were
      determined and compared with those of previously reported BVDV 1 and 2. The
      isolates were clearly shown to belong to BVDV 2, not to BVDV 1.

PMID- 9646458
TI  - Detection of acid production from carbohydrates by Riemerella anatipestifer and
      related organisms using the buffered single substrate test.
AB  - One hundred and twenty-one Riemerella anatipestifer field strains from wild
      birds, domesticated poultry and pigs were examined for their ability to produce
      acid from carbohydrates by using conventional biochemical and buffered single
      substrate (BSS) test methods. The type strains of the species R. anatipestifer
      and taxometrically related genera Chryseobacterium and Bergeyella were included
      in the study. In contrast to 10 indole-positive R. anatipestifer variant strains,
      only a few of the 111 typical indole-negative R. anatipestifer strains produced
      acid from dextrin (32%), glucose (17%), maltose (14%) and trehalose (5%) when the
      conventional test procedure was used. Using the BSS test all the field isolates
      and the type strain of R. anatipestifer produced acid from one or more
      carbohydrates, most of them from dextrin (96%), maltose (91%), glucose (87%),
      mannose (83%), less frequently from fructose (38%) and only in some cases from
      trehalose (19%). One hundred and six (87%) of the R. anatipestifer strains could
      be assigned to 8 biovars, based on the diversity of the carbohydrate
      acidification patterns. The remaining 16 R. anatipestifer isolates gave delayed
      reactions and displayed 13 different carbohydrate acidification profiles. The
      Chryseobacterium and Bergeyella type strains also produced acid from more
      carbohydrates when the BSS test was used. The BSS-carbohydrate acidification
      pattern of the Chryseobacterium indologenes strain was similar to that of R.
      anatipestifer biovar 3.

PMID- 9646459
TI  - The frequent detection of a treponeme in bovine digital dermatitis by
      immunocytochemistry and polymerase chain reaction.
AB  - A study was carried out to determine whether spirochaetes are frequently
      associated with digital dermatitis in United Kingdom (UK) dairy cattle.
      Histopathological examination of lesions using a silver stain showed a large
      number of unidentified spirochaete-like organisms present in digital dermatitis
      hoof skin tissue in all examined biopsies. Immunocytochemical staining
      demonstrated that spirochaetes in skin lesions were identified by polyclonal
      antisera to Borrelia burgdorferi, Treponema denticola and Treponema vincentii
      (again all biopsies were positively stained), whereas monoclonal antibodies to B.
      burgdorferi and any Treponema pallidum did not stain any organisms in all
      biopsies. A PCR of 16S rRNA, previously shown to be specific for a new treponeme,
      was employed and produced positive results from 82.4% of digital dermatitis
      tissues. It is concluded that this spirochaete (or related spirochaetes), which
      is similar to human oral treponemes, is frequently associated with, and may be
      responsible for, pathological changes in digital dermatitis.

PMID- 9646460
TI  - Presence of papillomavirus-like DNA sequences in cutaneous fibropapillomas of the
      goat udder.
AB  - Papillomatous lesions were isolated from the mammary skin of goats and examined
      for evidence of papillomavirus (PV) infection by various criteria, including
      gross morphology, histology and DNA hybridization. Although some lesions showed
      gross papillomatous morphological and histological features similar to those
      caused by papillomavirus in other species, no viral particles were detected.
      Reverse slot hybridization revealed cross-hybridization between DNA extracted
      from goat mammary papillomas and human papillomaviruses (HPV). Southern blot,
      using ovine papillomavirus (OPV) and bovine papillomavirus type 5 (BPV 5) DNA
      probes under conditions of reduced stringency (Tm -40 degrees C), detected
      homologous sequences in 40% of the biopsies. DNA fragments corresponding probably
      to a monomeric form (7000-8000 bp) of an unknown papillomavirus genome were
      detected. This study provides evidence for the existence of papillomavirus-like
      sequences in caprine mammary papillomas and suggests that a papillomavirus is
      likely to be involved in the development of precancerous lesions of goat mammary
      skin.

PMID- 9646461
TI  - Promoter activity of sequence located upstream of the pseudorabies virus early
      protein 0 gene.
AB  - Promoter activity of the 5'-flanking region of the pseudorabies virus (PRV) early
      protein 0 (EP0) gene was analysed by transient transfection assays employing
      chloramphenicol acetyl transferase (CAT) reporter constructs. We identified a 213
      bp segment of the viral genome that was capable of efficiently driving expression
      of the EPO gene and a linked reporter gene upon transient transfection into Vero
      cells. This segment lacked the typical TATA element, and possessed an initiator
      element and the putative binding sites for the transcription factor Sp1 and
      immediate-early protein IE180, a strong transactivator of PRV. By analysing 5'
      deletion mutants of the segment, a 48 bp segment (from nucleotide positions -65
      to -17), which possessed three Sp1 binding sites, was identified to be critical
      for the promoter activity. Cotransfection of Vero cells with the mutant
      constructs and an IE180 expression plasmid resulted in transactivation of only
      those constructs in which the Sp1 sites were present. These results indicate that
      the EP0 gene may be transcribed from the TATA-less promoter that responds to Sp1.

PMID- 9646462
TI  - Experimental inoculation of swine at various stages of gestation with a Danish
      isolate of porcine reproductive and respiratory syndrome virus (PRRSV).
AB  - Following intranasal inoculation of three groups of pregnant swine (in total 11
      dams) with a Danish isolate of porcine reproductive and respiratory syndrome
      virus (PRRSV) on or about day 85, 70 and 45 of gestation, respectively,
      reproductive disturbances were observed in the first two groups. Transplacental
      transmission of PRRSV occurred in four out of five litters from dams inoculated
      around day 85 of gestation and in two out of three litters from dams inoculated
      on day 72 of gestation. In the third group, inoculated around day 45 of
      gestation, transplacental infection could not be demonstrated. Thirty-two (56%)
      piglets from dams inoculated on day 85 of gestation and 14 (33%) piglets from
      dams inoculated on day 72 of gestation, were transplacentally infected. Sixteen
      (28%) and six (14%) piglets, respectively, in these groups became infected in the
      perinatal period. Thirty-two (56%) piglets from dams inoculated on day 85 of
      gestation were stillborn or died within a 6-8 weeks observation period, 29 being
      stillborn or dying within the first two weeks of observation. Thirteen (30%)
      piglets from dams inoculated on day 72 of gestation died within the two weeks
      observation period. The duration of the viraemic phase varied considerably, from
      one day to four weeks, for both dams and their offspring. Most frequently, PRRSV
      was isolated from lung and/or tonsil tissues from dead and euthanized piglets
      younger than 14 days of age. Histopathological investigations of piglets
      typically revealed focal nonsuppurative inflammatory conditions, especially in
      the lung and heart. In conclusion, the present results support the hypothesis,
      that PRRSV infection of dams late in pregnancy has the greatest likelihood of
      transplacental infection of fetuses.

PMID- 9646463
TI  - Antimicrobial susceptibility testing of Mycoplasma hyosynoviae isolated from pigs
      during 1968 to 1971 and during 1995 and 1996.
AB  - This study was conducted to compare the Minimal Inhibitory Concentrations (MICs)
      for enrofloxacin, lincomycin, tetracycline, tiamulin and tylosin, of Mycoplasma
      hyosynoviae, isolated from pigs at notably different intervals (1968-71 and 1995
      96). Each group comprised 21 low passage isolates and a Danish reference strain
      (M60) and the type strain (S16). MICs were determined in liquid medium with both
      initial and final readings. Enrofloxacin, lincomycin, tetracycline and tiamulin
      were active against all isolates, and tiamulin showed the highest activity. For
      tylosin all the isolates from 1968-71 were highly susceptible, whereas the
      isolates from 1995-96 could be divided into a highly susceptible (nine isolates)
      and relatively resistant (12 isolates) group. This difference between old and new
      strains was statistically significant (p = 0.0000415). The remaining agents,
      enrofloxacin, lincomycin, tiamulin and tetracycline, showed an unaltered good
      activity against M. hyosynoviae. The resistance to tylosin seems now to occur so
      often that this antibiotic cannot be recommended for therapeutic use any more.
      The most probable explanation for the emergence of resistance is the intensive
      use of tylosin during many years for therapy and growth promotion.

PMID- 9646464
TI  - Utility of an internal control for evaluation of a Mycoplasma meleagridis PCR
      test.
AB  - Mycoplasma meleagridis, a turkey pathogen, can be detected by PCR directly from
      tracheal or genital swabs. However, up to 40% samples may contain inhibitory
      substances. A DNA fragment, that can be amplified with M. meleagridis primers and
      in the same cycling conditions, was constructed to use as an internal control
      (IC) to check for these inhibitors. This IC can easily be distinguished from the
      M. meleagridis amplicon after agarose gel electrophoresis since it is longer. Use
      of this IC in PCR amplifications revealed that more than 35% of turkey tracheal
      swabs and more than 45% of turkey cloacal swabs contained inhibitors. In most
      cases, dilution (1:100) of swab lysates allowed amplification of the internal
      control but DNA purification may be necessary to eliminate inhibitors (20% of
      tracheal swabs and 5% of cloacal swabs). Use of this internal control DNA allowed
      assessment of the efficiency of each individual reaction and ensured that the
      reaction was not inhibited by interfering substances.

PMID- 9646465
TI  - Binding characteristics of purified Escherichia coli K88ab fimbriae to guinea pig
      erythrocyte membrane.
AB  - The characteristics of the binding of biotinylated E. coli K88ab fimbriae to
      guinea pig erythrocyte membranes, as a possible model of the target host cell
      were studied. Binding showed sigmoidal dependence, with an apparent saturation at
      about 0.8 ng of fimbriae. Hill coefficient values (h) were about 2-2.4, which
      indicated that the receptor population showed positive cooperativity with at
      least three binding sites. Apparent binding constants to the first and third
      binding sites (1K3 and 3K3) were determined. Three K88ab binding proteins, of 67,
      63 and 48 kDa, were identified on solubilized erythrocyte membranes and were
      recovered mainly in a detergent phase, suggesting a possible integral
      localization of the receptors.

PMID- 9646466
TI  - Detection of virulent Rhodococcus equi in tracheal aspirate samples by polymerase
      chain reaction for rapid diagnosis of R. equi pneumonia in foals.
AB  - Polymerase chain reaction (PCR)-based assays were developed to detect virulent
      Rhodococcus equi in transtracheal aspirate samples from sick foals showing
      respiratory signs. An oligonucleotide primer pair from the sequence of the
      virulence-associated 15- to 17-kDa antigen gene of the virulence plasmid in
      virulent R. equi was used to amplify a 564 bp region by PCR, and the result was
      confirmed by Southern blot hybridization. No positive reaction was seen in DNA
      from 13 different microorganisms typically found in the respiratory tract. In
      tracheal aspirates seeded with virulent R. equi, a visible band could detect 10
      to 10(2) bacteria per PCR assay (10(3) to 10(4)/ml of the aspirate). Virulent R.
      equi was demonstrated in 31 of 42 transtracheal aspirates by culture and colony
      blot analysis, whereas a positive PCR result was observed in only 12 of the 31
      culture positive samples. To prevent false-negative results, two methods were
      developed: a nested PCR and a PCR in combination with enrichment cultures of
      aspirates in the selective medium to increase the number of bacteria to 10(4)/ml
      or more. All of the PCR-negative and culture-positive samples were positive by
      the two methods. These results indicated that PCR-based assays provide a specific
      and sensitive means to detect virulent R. equi in tracheal aspirates of foals,
      and they are more rapid than the routine culture procedures for the diagnosis of
      R. equi pneumonia in foals.

PMID- 9646467
TI  - Rapid diagnosis and strain differentiation of Mycobacterium bovis in radiometric
      culture by spoligotyping.
AB  - An assessment of spoligotyping for rapid detection and strain typing of
      Mycobacterium bovis isolates in radiometric culture was made. Spoligotyping was
      applied to BACTEC 12B broth cultures of 54 lesioned bovine lymph node specimens
      from 44 herds in Northern Ireland. A nucleic acid sequence capture technique was
      performed on BACTEC cultures at growth index points of approximately
      (approximately) 60, approximately 200, and 999. Definitive spoligotype patterns
      were obtained for 90.4% and 94.2% of all 52 BACTEC culture-positives at growth
      indexes approximately 60 and approximately 200, respectively. Within 10 days,
      definitive spoligotype patterns were obtained for 84.6% of the culture-positives.
      This technique, therefore, allowed earlier and more accurate diagnosis of M.
      bovis than traditional methodologies, as well as simultaneous strain
      differentiation. Application of this molecular tool to BACTEC cultures would be a
      significant advance in bovine tuberculosis eradication programmes. Seven distinct
      spoligotype patterns were identified in this study, 2 of which (ST21 and ST25),
      had not been identified previously in cattle from Northern Ireland. Two
      spoligotype patterns (ST1 and ST2) accounted for 80.7% of the culture-positives.
      These were found to have widespread geographic distribution, whereas 1
      spoligotype pattern (ST14) had limited geographical distribution.

PMID- 9646468
TI  - Bovine platelet adhesion is enhanced by leukotoxin and sialoglycoprotease
      isolated from Pasteurella haemolytica A1 cultures.
AB  - Platelet and fibrin deposits are among characteristic changes observed in lung
      alveoli of cattle with pasteurellosis induced by Pasteurella haemolytica (biotype
      A, serotype 1). To determine whether the platelet function could be directly
      affected by protein products produced by the bacterium, the effects of leukotoxin
      and O-sialoglycoprotease, culture supernatant antigen secreted by Pasteurella
      haemolytica A1, on bovine platelet activation were examined by evaluating the
      enhancement of platelet adhesion to a negatively charged surface relative to
      untreated control samples. The glycoprotease, or the leukotoxin, was added to
      plasma free suspensions of bovine platelets and platelet adhesion assessed by two
      parameters: (i) the number of 3H-adenine-labeled adherent platelets and (ii) the
      morphology of unlabeled platelets adhering to the charged surface under scanning
      electron microscopy (SEM). In the presence of calcium, the glycoprotease produced
      a dose-dependent increase in adhesion. At a concentration of 4.0 micrograms
      glycoprotease extract protein per 10(7) platelets, a 2-fold increase in adhesion
      was observed which was similar to the increase in adhesion induced by 0.10 units
      of thrombin, a known platelet agonist. Both increased platelet adhesion and
      platelet aggregation were observed with 0.8 microgram glycoprotease extract
      protein in the presence of calcium. The response of the bovine platelet
      suspensions to leukotoxin extract protein was dependent on the dosage of the
      leukotoxin. Adhesion was enhanced at dosages of 25 micrograms leukotoxin protein
      per 10(7) platelets and below, while at dosages of 50 micrograms and above
      adhesion was suppressed. Thus, the two proteins secreted by P. haemolytica may
      interact directly with bovine platelets to initiate platelet aggregation and
      fibrin formation in alveolar tissue in pneumonic pasteurellosis.

PMID- 9646469
TI  - Potential virulence factors of Streptococcus dysgalactiae associated with bovine
      mastitis.
AB  - Mastitis caused by environmental pathogens is a major problem that affects many
      well-managed dairy herds. Among the environmental pathogens, Streptococcus
      dysgalactiae is isolated frequently from intramammary infections during lactation
      and during the nonlactating period. In spite of its high prevalence, little is
      known about factors that contribute to the virulence of S. dysgalactiae. During
      the last decade, several cell-associated and extracellular factors of S.
      dysgalactiae have been identified; yet, the relative importance of these factors
      in the transmission and pathogenesis of mastitis caused by S. dysgalactiae has
      not been defined. Streptococcus dysgalactiae can interact with several plasma and
      extracellular host-derived proteins such as immunoglobulin G, albumin,
      fibronectin, fibrinogen, collagen, vitronectin, plasminogen, and alpha 2
      macroglobulin. These interactions are mediated by bacterial surface proteins.
      This organism also produces hyaluronidase and fibrinolysin which may be involved
      in promoting dissemination of the organism into host tissue. Streptococcus
      dysgalactiae adheres to and is internalized by bovine mammary epithelial cells in
      vitro. Involvement of host cell kinases, intact microfilaments and de novo
      eukaryotic protein synthesis are required for internalization of S. dysgalactiae
      into bovine mammary epithelial cells; a process that appeared to occur by a
      receptor-mediated endocytosis mechanism. However, de novo bacterial protein
      synthesis was not required for epithelial cell internalization. Furthermore, S.
      dysgalactiae survived within mammary epithelial cells for extended periods of
      time without losing viability or damaging the eukaryotic cell. Further research
      on characterization of host-pathogen interactions that take place during the
      early stages of mammary gland infection will enhance our understanding of
      pathogenesis of intramammary infection which may contribute to development of
      methods to minimize production losses due to mastitis.

PMID- 9646471
TI  - The interaction of Streptococcus dysgalactiae with plasmin and plasminogen.
AB  - The activation of plasminogen and the binding of plasmin by bacteria may have
      many effects which promote infection. The occurrence of such activities in
      streptococci is well documented; however, these are yet to be demonstrated for S.
      dysgalactiae. Consequently, the ability of this bacterium to activate mammalian
      plasminogen and bind either plasmin or its zymogen was investigated. Activation
      of bovine plasminogen was dependent on both the strain and the growth medium used
      for cultivation. Eighteen strain were able to activate bovine and ovine
      plasminogen and some of these also activated plasminogen from the horse, rabbit
      and pig. None activated human plasminogen and one strain (CE127) did not activate
      plasminogen from any source. Tricine-SDS PAGE and zymographic analysis of culture
      supernatants showed that bovine plasminogen was activated by four out of six
      strains at two locations corresponding to 16 kDa and 10 kDa. Following the growth
      of five strains in the presence of bovine plasminogen, all but strain CE127 bound
      high levels of plasmin activity. In contrast, following growth in human
      plasminogen none of the strains exhibited bound plasmin activity although all
      could bind human plasmin directly. All strains were also able to bind bovine and
      human plasminogen in such a way as to allow its activation by urokinase. We
      conclude that S. dysgalactiae is capable of activating mammalian plasminogen in a
      species-specific fashion and that the bacterium is also capable of binding
      plasmin and plasminogen with an apparent preference for bovine plasmin over human
      plasmin and/or plasminogen from either species.

PMID- 9646470
TI  - Spacer oligotyping of Mycobacterium bovis isolates compared to typing by
      restriction fragment length polymorphism using PGRS, DR and IS6110 probes.
AB  - Ninety-two Mycobacterium bovis isolates from cattle, deer and badgers in Northern
      Ireland and the Republic of Ireland were genotyped by spacer-oligotyping
      (spoligotyping) and 67 of these were analysed by restriction fragment length
      polymorphism (RFLP). RFLP analysis was performed using three DNA probes, PGRS, DR
      and IS6110. Forty-seven of the M. bovis isolates were from 45 different sources;
      these were typed using both RFLP and spoligotyping. These 47 isolates could be
      differentiated into 24 different RFLP types and 15 distinct spoligotypes.
      Although RFLP was found to be more discriminatory compared to the present
      spoligotyping technique, spoligotyping was able to differentiate 21 RFLP type
      'ACA' isolates into three different patterns. The remaining 45 M. bovis isolates
      were from a small case study, involving infected cattle, deer and badgers from
      the same geographic region. All these isolates were analysed by spoligotyping and
      a selection of 20 isolates were RFLP typed. All the isolates in the case study
      had the same spoligotype pattern with the exception of one cervine isolate.
      Similarly all the isolates typed by RFLP had the same pattern. Consequently, the
      predominant strain in the case study was not host restricted. The consistency
      between the results obtained using the two techniques indicates the potential
      value of both techniques for epidemiological studies. Spoligotyping was found to
      be a much more rapid technique and easier to perform, requiring less
      sophisticated computer software for strain typing. Spoligotyping results were
      more readily documented and analysed and the technique was also more suitable
      than RFLP analysis for large-scale screening studies.

PMID- 9646472
TI  - Prevalence of verotoxin-producing Escherichia coli harbored in the intestine of
      cattle in Japan.
AB  - The production of verotoxin was examined in 2152 Escherichia coli isolates from
      387 cattle in Japan from 1992 to 1994. The toxin was detected in 263 isolates
      from 94 cattle (detection rate: 24.3%). Verotoxin-producing E. coli (VTEC) was
      isolated from the cattle in 15 out of 17 prefectures, and the strains were
      divided into 33 serotypes. E. coli O157:H7 was isolated from 7 out of 387 cattle
      (detection rate: 1.8%) in four prefectures. These results suggest that VTEC is
      widely distributed in Japan and include a wide variety of serotypes.

PMID- 9646473
TI  - Tularemia in a common marmoset (Callithrix jacchus) diagnosed by 16S rRNA
      sequencing.
AB  - We report a case of tularemia in a common marmoset (Callithrix jacchus) diagnosed
      by determination of the isolate's 16S ribosomal RNA (rRNA) gene sequence.
      Pathological examination of the animal revealed a multifocal acute necrotizing
      hepatitis, interstitial nephritis, splenitis, and lymphangitis of the mandibular,
      retropharyngeal, and cervical and mesenteric lymph nodes. Moreover, multiple foci
      of acute necrosis were found in the epithelium of the jejunum and the
      interstitium of the lung. Bacteriological investigations revealed a septicemia.
      The isolated infectious agent was uncommon, not routinely diagnosed in our
      laboratory and therefore difficult to identify by conventional tools in a
      reasonable time and effort. thus, we decided to perform a genetic analysis based
      on the 16S rRNA gene sequence. Thereby, an infection with Francisella tularensis,
      the causative agent of tularemia, was unambiguously diagnosed. This shows the
      great advantage 16S rRNA gene sequencing has as a general identification approach
      for unusual or rare isolates.

PMID- 9646474
TI  - Replication of bovine respiratory syncytial virus in bovine and ovine peripheral
      blood lymphocytes and monocytes and monocytic cell lines.
AB  - The present study compared the replication of bovine respiratory syncytial virus
      (BRSV) in bovine and ovine peripheral blood mononuclear cells, ovine and bovine
      monocytic cell lines and ovine alveolar macrophages. Low titres of virus were
      detected in ovine and bovine lymphocytes and monocytes 24-96 h post-exposure to
      the virus but there was no apparent replication of the virus in ovine alveolar
      macrophages during the culture period. The virus replicated to higher but
      statistically insignificant titres in ovine and bovine peripheral blood monocytes
      than in lymphocytes, with lymphocytes yielding peak titres significantly earlier.
      The secondary cell lines obtained from ovine liver and bone marrow also supported
      the replication of BRSV to high titres. The titres of BRSV in ovine and bovine
      lymphocytes and monocytes were significantly lower than in secondary cell lines.
      The addition of human recombinant tumour necrosis factor alpha after exposure to
      the virus or pre-incubation of ovine or bovine monocytic cells with either human
      recombinant interleukin 2 or phorbol myristate acetate before exposure to BRSV,
      did not significantly affect virus titre. Pre-incubation of cells with
      indomethacin or actinomycin significantly lowered virus titre (p < 0.05).

PMID- 9646475
TI  - Evaluation of baculovirus-expressed bovine herpesvirus-1 (BHV-1) glycoproteins
      for detection and analysis of BHV-1-specific antibody responses.
AB  - Baculovirus (Autographa californica nuclear polyhedrosis)-expressed bovine
      herpesvirus-1 (BHV-1) glycoproteins B (gB), gC, and gD were developed and
      characterized. The recombinant proteins retained their antigenic properties as
      determined by immunoblotting against monoclonal antibodies. The proteins were
      examined as antigens for detection of BHV-1 infection and for the analysis of
      antibody responses to the individual viral proteins. A total of 115 bovine serum
      samples were tested for their reactivity with individual recombinant proteins
      from baculovirus-infected Spodoptera frugiperda (SF-9) cell lysates by enzyme
      linked immunosorbent assay (ELISA), western blotting, and dot blotting assays.
      These serum samples were previously tested for BHV-1-specific antibodies by virus
      neutralization (VN) at the veterinary diagnostic laboratory. All 90 serum samples
      tested positive with VN were positive by ELISA against gC and gD, separately.
      However, reactivities of sera against gB were generally low and inconsistent. On
      the other hand, out of 25 sera that were negative with VN, 22 sera were
      consistent and gave negative results against gC or gD by ELISA, whereas
      reactivities with gB were inconsistent. Similar results were obtained when the
      sera were tested by western blotting and dot blotting. The positive sera
      consistently reacted strongly against gC and to a lesser extent gD. These results
      suggest that baculovirus expressed gC from infected cell lysate can be used as a
      potential diagnostic antigen for detection of anti-gC-specific antibody responses
      in BHV-1 infected cattle.

PMID- 9646476
TI  - Immune responses and protective efficacy of recombinant baculovirus-expressed
      glycoproteins of equine herpesvirus 1 (EHV-1) gB, gC and gD alone or in
      combinations in BALB/c mice.
AB  - Baculovirus-expressed glycoproteins of EHV-1 gB, gC and gD alone or in
      combination evoked antibody responses and protected vaccinated mice against a
      challenge with EHV-1. gB, gD, gB + gC, gB + gD and gC + gD elicited very high
      levels of ELISA antibodies while gC and gC + gD elicited high levels of virus
      neutralising antibodies. Western blotting demonstrated that the antibodies
      produced were not only specific for the baculovirus-expressed glycoproteins gB,
      gC and gD, but also highly specific for each EHV-1 glycoprotein. Vaccination of
      mice with gB or gD prevented clinical signs of infection in mice challenged with
      EHV-1 and all vaccinated groups of mice except controls showed a rapid clearance
      of virus from the lungs and a reduction in lesions characteristic of
      herpesviruses in the lungs post-challenge. Notably, the lungs of mice vaccinated
      with gB, gD or gB + gD and challenged with EHV-1 showed prominent peribronchiolar
      and perivascular aggregations of mononuclear cells, predominantly lymphocytes.
      Immunocytochemical staining of these sections showed large numbers of T cells,
      suggesting an active role for these cells at the site of virus replication post
      challenge.

PMID- 9646477
TI  - Susceptibility of alpine ibex to conjunctivitis caused by inoculation of a sheep
      strain of Mycoplasma conjunctivae.
AB  - We evaluated the susceptibility of alpine ibex (Capra ibex ibex) to mycoplasmal
      conjunctivitis induced by a strain of Mycoplasma conjunctivae isolated from
      domestic sheep by inoculation of three alpine ibexes with 1.2 x 10(6) colony
      forming units of M. conjunctivae in the conjunctival sac of both eyes. One more
      ibex was exposed to the infection by contact. Experimental animals were free of
      M. conjunctivae and ocular Chlamydia infection before inoculation. Conjunctivitis
      and serous to mucous lachrymation became apparent in all four ibexes. Clinical
      signs began within 2 days in inoculated animals and 22 days after the beginning
      of the experiment in the contact ibex. M. conjunctivae was demonstrated up to the
      63th day post-inoculation by cultural and PCR-methods. After 63 days,
      histopathologic examination revealed nearly normal ocular tissues, and M.
      conjunctivae could be detected from two eyes only. No other infectious agents
      which might cause conjunctivitis or keratitis, including Chlamydia psittaci and
      Branhamella ovis, were involved. Our investigation indicates that sheep-strains
      of M. conjunctivae can induce conjunctivitis in alpine ibex, thus showing
      pathogenicity of this organism for Caprinae species other than domestic sheep and
      goats.

PMID- 9646478
TI  - Biochemical and biological characterizations and ribotyping of Actinomyces
      pyogenes and Actinomyces pyogenes-like organisms from liver abscesses in cattle.
AB  - Actinomyces pyogenes is the second most frequently encountered pathogen, next
      only to Fusobacterium necrophorum, in liver abscesses of feedlot cattle. Ninety
      one isolates, presumptively identified as A. pyogenes, isolated from liver
      abscesses of cattle were studied. Biochemical characteristics determined by the
      API 20 Strep kit were similar to those reported previously for A. pyogenes
      isolated from other infections, except that 18% of isolates hydrolyzed esculin.
      Nine isolates that resembled A. pyogenes in morphology and in certain biochemical
      characteristics, but fermented mannitol and/or raffinose, were called A. pyogenes
      like (APL) organisms. The five antimicrobial agents, bacitracin,
      chlortetracycline, oxytetracycline, tylosin, and virginiamycin were inhibitory to
      all strains of A. pyogenes and APLs. Generally, APL organisms had higher mean
      hemolytic and leukotoxic activities than A. pyogenes. All isolates of A. pyogenes
      and APLs produced proteases and neuraminidases. Ribotyping with endonucleases,
      including BstEII, ClaI, EcoRI, EcoRV, HaeIII, MboI, PvuII, SalI, and SmaI alone
      or in combinations, showed considerable genetic heterogeneity in both A. pyogenes
      and APLs. No specific ribopattern characteristic of each group was observed with
      any of the endonuclease used. The origin of A. pyogenes and APLs and the relative
      importance of APLs in causing liver abscesses in feedlot cattle are not known.

PMID- 9646479
TI  - Antimicrobial susceptibility of Moraxella bovis.
AB  - The antimicrobial susceptibility of 55 isolates of Moraxella bovis to seven
      antibiotics was evaluated by broth microdilution procedures. The isolates had an
      MIC90 of < or = 1 mg/l to erythromycin, ceftiofur, and ampicillin; 4 mg/l to
      tilmicosin; 16 mg/l to tylosin and gentamicin; and had MIC90s of > or = 32 mg/l
      for oxytetracycline. The modal MIC values for these antibiotics were as follows:
      ampicillin, < 0.25 mg/l; ceftiofur, < or = 0.125 mg/l; tilmicosin, 2 mg/l;
      tylosin, 8 mg/l; erythromycin 1 mg/l; oxytetracycline, < or = 0.5 mg/l; and
      gentamicin, < or = 0.5 mg/l. This in vitro data showed most antibiotics have low
      MICs that are suggestive of clinical efficacy.

PMID- 9646480
TI  - Restriction fragment length polymorphism and spacer oligonucleotide typing: a
      comparative analysis of fingerprinting strategies for Mycobacterium bovis.
AB  - The combination of conventional investigation and DNA fingerprinting is yielding
      important insights into the epidemiology of Mycobacterium bovis infections.
      Various genetic markers used in restriction fragment length polymorphism (RFLP)
      have recently been exploited for fingerprinting of M. bovis isolates. The newly
      developed spacer oligonucleotide typing aimed to investigate the polymorphism of
      M. tuberculosis in the DR locus, has also been applied to the molecular typing of
      M. bovis isolates. This work compared the performance of the insertion sequence
      (IS) IS6110, IS1081 and the genetic elements polymorphic G + C-rich repeat (PGRS)
      and direct repeat (DR) used in RFLP analysis with spoligotyping using a group of
      128 Spanish M. bovis isolates. In this study, the most sensitive technique for
      identifying polymorphism in M. bovis was PGRS-RFLP, closely followed by IS6110
      RFLP. We propose several schemes for fingerprinting of these isolates, however,
      the clear geographical variations found by different authors makes the study of
      each local situation indispensable. An international consensus in the methods
      used would be desirable for efficient interlaboratory comparison of strains.

PMID- 9646481
TI  - Fragrance compounds and amphiphilic association structures.
AB  - Fragrance formulations have traditionally been based on alcohol as the solvent,
      but the recent legal restrictions on volatile organic solvents have prompted the
      industry to change to aqueous solubilized systems. The article reviews the
      fundamental factors in the application of such systems evaluating the influence
      by different amphiphilic association structures on the vapor pressure of
      fragrance compounds. This information is subsequently used to estimate the
      variation of fragrance compound vapor pressures during evaporation. The results
      reveal that the vapor pressure versus time variation is improved compared to
      solvent-based formulations.

PMID- 9646482
TI  - Sintered octadecylsilica as monolithic column packing in capillary
      electrochromatography and micro high-performance liquid chromatography.
AB  - Fused-silica capillaries were packed with porous 6-microns octadecylated silica
      microspheres and subjected to thermal treatment in order to obtain a column with
      porous silica based monolithic packing. After sintering, the monolithic packing
      was reoctadecylated in situ with dimethyloctadecylchlorosilane. The mechanical
      strength and stability of the monolithic column were significantly greater than
      those of conventional columns packed with particulate stationary phase. The
      performance of the columns was evaluated in both mu-HPLC and capillary
      electrochromatography (CEC) of small aromatic compounds and polycyclic aromatic
      hydrocarbons with 10 mM borate, pH 8.0, in acetonitrile-water mixtures as the
      mobile phase. Since no untoward bubble formation was observed, CEC could be
      performed in a CZE unit without the need for pressurizing the monolithic column.
      The plate efficiency of the monolithic column was similar to that of columns
      freshly packed with the same particles and was always higher in the CEC than in
      the mu-HPLC under otherwise identical conditions. The electrosmotic flow (EOF)
      velocity increased with the acetonitrile content of the eluent in open fused
      silica capillaries with octadecylated innerwall and in columns packed with
      sintered octadecylsilica. In contradistinction, the EOF velocity decreased with
      the organic strength of the eluent in raw fused-silica capillaries. The opposite
      trend is attributed to the different effect of changing organic modifier
      concentration on the accessibility of silanol groups at the raw and octadecylated
      silica surfaces.

PMID- 9646483
TI  - Optimal membrane choice for microdialysis sampling of oligosaccharides.
AB  - An analytical methodology based on microdialysis sampling, high-performance anion
      exchange chromatography and integrated pulsed electrochemical detection for the
      monitoring of oligosaccharides in bioprocesses is presented. Amylopectin and
      model maltooligosaccharide standards; glucose, maltose, maltotriose,
      maltotetraose, maltopentaose, maltohexaose and maltoheptaose were used to
      demonstrate its versatility in view to sampling in enzymatic bioprocesses. The
      performance and characteristics of membranes with the same cut-off ranging
      between 3 and 100 kDa, were evaluated with respect to their extraction fraction
      (EF), permeability factors, temperature stability and protein (enzyme)
      interaction. All investigated membranes showed some non-specific interaction with
      enzymes. The EF and non-specific membrane-enzyme interactions were higher for the
      polysulfone membranes compared with the polyamide and polyethersulfone membranes.
      For all saccharides, the EF was independent of the concentration even for a 250
      fold change in concentration. The EF and morphology of the membranes in their
      dehydrated state, as observed using scanning electron microscopy did not show any
      significant difference between membranes exposed to a 90 degrees C temperature
      for 3 and 24 h indicating their applicability to the study of high temperature
      bioprocesses.

PMID- 9646484
TI  - Enrichment and purification of proteins of Haemophilus influenzae by
      chromatofocusing.
AB  - Haemophilus influenzae is a bacterium of pharmaceutical interest of which the
      entire genome has been sequenced. Identification of low-abundance proteins in a
      two-dimensional map is important for the detection of new drug targets. We
      applied chromatography on Polybuffer Exchanger (chromatofocusing) in order to
      fractionate and enrich H. influenzae proteins, possibly low-copy-number gene
      products, from larger volumes. Two proteins, major ferric iron-binding protein
      (HI0097) and 5'-nucleotidase (HI0206) were obtained in pure form and hypothetical
      protein HI0052 was purified to near homogeneity by this single purification step.
      Four other proteins, aspartate ammonia lyase (HI0534), peptidase D (HI0675),
      elongation factor Ts (HI0914) and 5-methyltetrahydropteroyltriglutamate
      methyltransferase (HI1702), were strongly enriched so that chromatography on
      Polybuffer Exchanger can be used as an initial step for their isolation.
      Approximately 125 proteins were identified in the fractions collected from the
      column. Seventy of these were for the first time identified after chromatography
      on Polybuffer Exchanger. The proteins enriched by the chromatofocusing step
      include both low-abundance as well as high-copy-number gene products. They do not
      belong to a single protein class and the majority of them are enzymes with
      various functions. The results include a list and a two-dimensional map of the
      proteins enriched by chromatofocusing. They may be useful in the search of drug
      targets and in the design of purification protocols for the isolation of
      homologous proteins from related microorganisms.

PMID- 9646485
TI  - Determination of ascorbic acid in food by column liquid chromatography with
      electrochemical detection using eluent for pre-run sample stabilization.
AB  - Determination of ascorbic acid (AA) in food was performed by column liquid
      chromatography with electrochemical detection using an eluent (100 mM KH2PO4 (pH
      3) with 1 mM ethylenediaminetetraacetic acid disodium dihydrate) for pre-run
      sample stabilization. The applied potential was set at 400 mV vs. an Ag/AgCl
      reference electrode. The proposed method was simple, rapid (analysis time: ca. 8
      min), sensitive (detection limit: ca. 0.5 ng per injection (20 microliters) at a
      signal-to-noise ratio of 3), highly selective and reproducible [relative standard
      deviation: ca. 1.8% (n = 5)]. The calibration graph for AA was linear in the
      range 0.1-16 ng per injection (20 microliters). Recovery of AA was over 90% by
      the standard addition method.

PMID- 9646486
TI  - Derivatization in capillary electrophoresis.
AB  - In recent years capillary electrophoresis (CE) has been developed into a
      versatile separation technique, next to gas and liquid chromatography (LC), well
      suited for the determination of a wide variety of e.g., pharmaceutical,
      biomedical and environmental samples. The main advantages of CE over
      chromatographic separation techniques are its simplicity and efficiency. It is
      well recognized, however, that the sensitivity and selectivity of the detection
      are relatively weak points of CE. One way to overcome these limitations is the
      conversion (derivatization) of the analytes into product(s) with more favourable
      detection characteristics. Although, in principle, almost any detection mode can
      be combined with a derivatization procedure, in practice, fluorescence monitoring
      is favoured in most cases. This paper aims to give a short overview on the
      various reagents that can be used for pre-, post- and on-column derivatization in
      CE. First, a short introduction is given on CE as an analytical technique,
      followed by a discussion of the pros and cons of the various modes of
      derivatization, a comparison of derivatizations in CE with derivatizations in LC,
      the principles of fluorescence and prerequisites for a good fluorophore and the
      potential of using diode lasers in combination with a labelling procedure. With
      respect to the derivatization reagents the emphasis is on the labelling of amino,
      aldehyde, keto, carboxyl, hydroxyl and sulfhydryl groups.

PMID- 9646487
TI  - Therapeutic drug monitoring by capillary electrophoresis.
AB  - Because of the ease of analysis and the high resolution, drug analysis is
      becoming the best example for the application of capillary electrophoresis.
      Therapeutic drug monitoring is a specialized area of drug analysis performed in
      clinical laboratories for patient care. CE offers high resolution and speed with
      the low operating costs needed in patient care. However, CE has a few
      limitations, mainly poor detection limits and precision. Simple methods of
      stacking, which enhance drug detection to overcome the poor sensitivity of CE are
      stressed. Serum has a unique matrix with a high content of proteins and salts
      which can have adverse effects on separation by CE. For successful analysis,
      special maneuvers are employed to decrease these matrix effects. Studies that
      have addressed the improvement of the precision of CE are summarized. CE offers
      the possibility of bringing chiral separations into the routine arena.

PMID- 9646488
TI  - Chiral analysis by capillary electrophoresis using antibiotics as chiral
      selector.
AB  - The separation of chiral compounds by capillary electrophoresis (CE) is a very
      interesting field of research in different areas such as pharmaceutical,
      environmental, agricultural analysis etc. The separation of two enantiomers can
      be achieved in CE using a chiral environment interacting with the two analytes on
      forming diastereoisomers with different stability constants and thus different
      mobilities. A wide number of chiral selectors have been employed in CE and among
      them glycopeptide antibiotics exhibited excellent enantioselective properties
      towards a wide number of racemic compounds. Vancomycin, ristocetin A, rifamycins,
      teicoplanin, kanamycin, streptomycin, fradiomycin, and two vancomycin analogues,
      added to the background electrolyte (BGE), are the antibiotics studied by CE
      running the separation in untreated and/or coated fused-silica capillary. Due to
      adsorption and absorption phenomena, some drawbacks can be expected when using
      bare fused-silica capillary, e.g., changes of electroosmotic flow (EOF), broaden
      peaks, reduced efficiency and low sensitivity. Coated capillary and counter
      current mode can be the solution to overcome the above mentioned problems. This
      review surveys the separation of enantiomers by CE when macrocyclic antibiotics
      are used as chiral selector. The enantioselectivity can be easily controlled
      modifying several parameters such as antibiotic type and concentration, pH, ionic
      strength and concentration of the background electrolyte, organic modifier etc.
      The paper also presents a list of the latest chiral separations achieved by CE
      where antibiotics were used as chiral selector.

PMID- 9646489
TI  - Application of capillary zone electrophoresis-inductively coupled plasma mass
      spectrometry and capillary isoelectric focusing-inductively coupled plasma mass
      spectrometry for selenium speciation.
AB  - The high resolution potential of capillary electrophoresis (CE) makes CE
      techniques valuable for separations of selenium species, both, organic and
      inorganic. Such effective separations of charged species are possible using the
      CZE mode (Z = zone). Very powerful separations can be achieved by capillary
      isoelectric focusing, when analysing molecules showing different isoelectric
      points (pI) values, such as organic Se species. Inductively coupled plasma (ICP)
      MS is an element-specific multi-element detector, providing extremely low
      detection limits. The combination of CE with ICP-MS promises a powerful tool for
      metal speciation. Therefore, an online hyphenation of CE [using capillary zone
      electrophoresis (CZE) or capillary isoelectric focusing (cITP) model] with ICP
      MS, which was developed earlier, was modified and applied to selenium speciation.
      Separation was differentiated from the detection step during hyphenation. This
      resulted in short separation times (10 min) and a subsequent detection step
      lasting 100 s. Firstly, a CZE method was applied, providing a separation of six
      Se species of interest in one run [Se(IV), Se(VI), selenium carrying glutathione
      (GSSeSG), selenomethionine (SeM), selenocystine (SeC), selenocystamine (SeCM)].
      This CZE method used an alkaline background electrolyte (Na2CO3/NaOH). The Se
      species were separated sufficiently from each other. Detection limits were
      calculated as 10 or 20 micrograms Se l-1 for inorganic Se species and 30-50
      micrograms Se l-1 for organic Se species. The method was applied to standard
      mixtures and body fluids like human milk and serum. Secondly, a cIEF separation
      (pH range 2-10) was employed for organic Se species only in parallel. Detection
      limits were around 10-30 micrograms Se l-1. The method was applied to standard
      mixtures and body fluids like human milk and serum.

PMID- 9646490
TI  - Thermal stability studies of immunoglobulins using capillary isoelectric focusing
      and capillary zone electrophoretic methods.
AB  - The affinity of an antibody towards its antigen is highly specific to its
      conformation, in order to have optimal antibody-antigen interaction. The increase
      of temperature might cause changes in antibody conformations. The change of
      structure conformations may be reflected in the isoelectric points (pI values),
      peak shape and absorbance of the antibody. In this study, a monoclonal antibody
      was heated over a period of time. Capillary isoelectric focusing (cIEF) and
      capillary zone electrophoresis (CZE) were used to monitor the change in the
      antibody. The longer the heating period, the lower the pI values were under cIEF
      conditions. CZE also showed changes in peak shapes and decreases in absorbance of
      the antibody with heating.

PMID- 9646491
TI  - Insulin stacking for capillary electrophoresis.
AB  - Stacking methods are very important in overcoming the poor detection limits in
      capillary electrophoresis. Human insulin, a polypeptide, was concentrated on the
      capillary (stacked) based on three different and simple treatment methods to the
      sample: dilute buffers, high salt content, and acetonitrile (66%) were added to
      the sample to induce stacking. A dilute buffer in the sample caused a limited
      stacking, while acetonitrile treatment and high salt content in the sample caused
      much greater (approximately 20-fold) stacking. High salt concentration in the
      sample caused stacking presumably by a transient isotachophoretic method. In
      addition to stacking, the acetonitrile treatment removed the excess proteins in
      the sample. Insulin did not denature or precipitate in 66% acetonitrile as
      confirmed by high-performance liquid chromatography (HPLC) and immunoassays.
      Acetonitrile treatment enabled one-third of the capillary to be loaded with
      sample thus increasing the detection signal greatly. The insulin peak after
      acetonitrile treatment and separation by capillary electrophoresis (CE) was
      confirmed by HPLC and by CE fraction collection followed by immunoassay. Based on
      acetonitrile treatment, insulin detection in pancreatic tissue homogenates is
      shown to be feasible.

PMID- 9646492
TI  - Capillary electrophoresis in biochemical and clinical laboratoriesp selected
      attractive examples.
AB  - As demonstrated by selected examples from our laboratories, CE is a unique
      methodology for purity control of synthetic as well as natural tissue-isolated
      biopolymers, a prerequisite before reliable biotestings should be performed. A
      combination of rapid matrix-assisted laser desorption ionization mass and CE
      electrophoretic mobility determinations facilitates primary sequence
      determinations of enzymatic peptide digest mixtures often making costly Edman
      degradations unnecessary. The enormous separation efficiency and large variety of
      different possible separation modes in CE, allow detection of single components
      in complex mixtures which is demonstrated by the apolipoprotein A-I determination
      in human blood serum in this communication.

PMID- 9646493
TI  - Trace chromatographic analysis of dimethyl sulfoxide and related methylated
      sulfur compounds in natural waters.
AB  - Dimethyl sulfoxide (DMSO) occurs in the environment as a result of a number of
      biogenic and anthropogenic production and emission processes. It is an
      environmentally significant compound because of its use as a substrate by
      bacteria and its potential role in the biogeochemical cycle of dimethyl sulfide
      (DMS), a climatically active trace gas. In this paper, current methods for DMSO
      determination at nanomolar levels in natural waters, all involving gas
      chromatography, are reviewed. Direct injection and separation of aqueous DMSO
      offers a simple and fast application, but exhibits limited sensitivity due to
      limitation on injection volumes. So far, most authors have preferred DMSO
      reduction and subsequent analysis of the evolved DMS by purge-and-trap
      preconcentration and flame photometric detection. Several reducing agents have
      been used, though some require cumbersome procedures or are very sensitive to
      operational conditions. The common algal component dimethylsulfoniopropionate
      (DMSP) acts as an interference in some reduction methods and, therefore, either
      DMSP elimination prior to DMSO analysis or correction a posteriori is required.
      DMSO can be analyzed along with DMS, methanethiol, dimethyl disulfide and DMSP in
      the same water sample, either sequentially or separately, so that comprehensive
      speciation of methylated sulfur is obtained. Owing to the biological activity of
      DMSO, appropriate water sampling and handling procedures must be applied.
      Acidification and freezing appear to be suitable for aqueous DMSO storage,
      although immediate analysis in the field is always preferable. Future directions
      of DMSO determination in aquatic environments are suggested.

PMID- 9646494
TI  - Characterization of large-pore polymeric supports for use in perfusion
      biochromatography.
AB  - Perfusion chromatography is uniquely characterized by the flow of a portion of
      the column eluent directly through the resin in the packed bed. The benefits of
      this phenomenon and some of the properties of perfusive resins have been
      described before, and can be summarized as enhanced mass transport to interior
      binding sites. Here we extend the understanding of this phenomenon by comparing
      resins with different pore size distributions. Resins are chosen to give
      approximately the same specific pore volumes (as shown in the characterization
      section) but the varying contribution of large pores is used to control the
      amount of liquid flowing through the beads. POROS R1 has the largest contribution
      of throughpores, and therefore the greatest intraparticle flow. POROS R2 has a
      lower contribution of throughpores, and a higher surface area coming from a
      greater population of diffusive pores, but still shows significant mass transport
      enhancements relative to a purely diffusive control. Oligo R3 is dominated by a
      high population of diffusive pores, and is used comparatively as a non-perfusive
      resin. Although the pore size distribution can be engineered to control mass
      transport rates, the resulting surface area is not the only means by which
      binding capacity can be controlled. Surface coatings are employed to increase
      binding capacity without fundamentally altering the mass transport properties.
      Models are used to describe the amount of flow transecting the beads, and
      comparisons of coated resins to uncoated (polystyrene) resins leads to the
      conclusion that these coatings do not obstruct the throughpore structures. This
      is an important conclusion since the binding capacity of the coated product, in
      some cases, is shown to be over 10-fold higher than the precursor polystyrene
      scaffold (i.e., POROS R1 or POROS R2).

PMID- 9646495
TI  - Comparison of diffusion and diffusion-convection matrices for use in ion-exchange
      separations of proteins.
AB  - A comprehensive study has been undertaken to characterise a range of
      chromatographic properties for a series of modified polystyrene-divinylbenzene
      (PS-DVB) chromatography matrices. The matrices studied included diffusion
      matrices and matrices that allowed convective mass transfer of liquid into the
      particles at high flow-rates, so-called "perfusion" matrices. The matrices tested
      included the following: CG1000sd 20-50 microns (TosoHaas), PLRP4000s 15-25
      microns, 50-70 microns (Polymer Labs.), Source 15RPC and 30RPC, 15S, 30S,
      (Pharmacia Biotech), POROS 20SP type 1 matrix and OH activated POROS 20 type 2
      matrix (PerSeptive Biosystems) and SP Sepharose Fast Flow (Pharmacia Biotech). A
      Van Deemter equation was used to determine bead tortuosities and split ratios.
      Frontal analysis, resolution studies, ionic capacities and isotherms were
      measured. It was found that diffusion-convection chromatographic particles had
      smaller plate heights to comparable diffusion particles. The smallest diffusion
      bead, Source 15, had the lowest plate heights at low superficial velocities, but
      the small particle size resulted in a high back pressure at high flow-rates. The
      equilibrium binding capacities for lysozyme and IgG on the diffusion-convection
      matrices were substantially lower than the equilibrium binding capacities on the
      diffusion matrices. The dynamic capacities for these proteins were also lower on
      the diffusion-convection particles, compared to the diffusion particles, over the
      tested flow-rates. At high protein loading, resolution between proteins was
      higher on diffusion particles than on diffusion-convection particles. Diffusion
      convection particles showed low or no resolution at high protein loading. At
      analytical level loadings, the diffusion-convection particles achieved a high
      resolution over the whole flow-rate range tested and were more suitable for this
      application than diffusion particles.

PMID- 9646496
TI  - Determination of 1-nitropyrene with enzyme-linked immunosorbent assay versus high
      performance column switching technique.
AB  - An enzyme-linked immunosorbent assay (ELISA) on microplates and a HPLC coupled
      column switching method were compared for the determination of the nitroarene
      compound 1-nitropyrene in airborne particulate organic matter collected at a busy
      intersection over a period of 2 months. After purification of the sample extract
      with silica, in the multidimensional chromatographic method nitroarenes were
      separated on a RP18 precolumn from matrix constituents followed by on-line
      reduction to corresponding aminoarenes with a Pt catalyst on alumina and a
      further separation of 1-aminopyrene on a second RP18 column. Methanol-water
      (70:30, v/v) was the mobile phase used. With ELISA, a six-fold overestimation was
      obtained for untreated samples. After clean-up it was lowered to approximately
      1.6-fold overestimation which was mainly caused by cross-reaction of 2
      nitropyrene and 2-nitrofluoranthene.

PMID- 9646497
TI  - Identification of main corticosteroids as illegal feed additives in milk
      replacers by liquid chromatography-atmospheric pressure chemical ionisation mass
      spectrometry.
AB  - Corticosteroids were proposed as growth promoting agents to improve commercial
      quality of meat. We developed a liquid chromatography-atmospheric pressure
      chemical ionisation mass spectrometry (LC-APCI-MS) method able to identify the
      presence in milk replacers, when given by mouth, of dexamethasone, betamethasone,
      flumethasone, triamcinolone, predinisotone, prednisolone, methylprednisolone,
      fludrocortisone and beclomethasone, at levels in the range of 20-100 ppb. C18
      solid-phase extraction, LC-RP C8 column separation, data acquisition (positive
      ions) in the scan range m/z 200-550 allowed us to differentiate and identify
      compounds by protonated molecules, their methanolic adducts and fragmentation
      patterns.

PMID- 9646498
TI  - Improved method for preparation and use of 9-anthryldiazomethane for
      derivatization of hydroxycarboxylic acids. Application to diarrhetic shellfish
      poisoning toxins.
AB  - Application of a method for the "in situ" generation of 9-anthryldiazomethane
      (ADAM) to the derivatization of the carboxyl function in diarrhetic shellfish
      poisoning (DSP) toxins revealed the formation of artifact products. Using liquid
      chromatography-mass spectrometry, it was determined that these artifacts were due
      to base-catalyzed reactions between the solvent, ethyl acetate, and the hydroxyl
      groups of the analyte to produce O-acetylated ADAM derivatives. Using a new
      formulation, with tetrahydrofuran as solvent, it was possible to eliminate these
      artifact reactions. Various reaction parameters have also been re-optimized to
      ensure quantitative derivatizations. An assessment method was developed that was
      useful not only for optimizing reaction parameters, but also for evaluating the
      reagent potency before use on important samples. Finally, application of the
      method to the determination of DSP toxins in plankton and mussel tissue was
      demonstrated.

PMID- 9646499
TI  - Determination of organoarsenicals in the environment by solid-phase
      microextraction-gas chromatography-mass spectrometry.
AB  - The development of a method for the analysis of organoarsenic compounds that
      combines dithiol derivatization with solid-phase microextraction (SPME) sample
      preparation and gas chromatography-mass spectrometry (GC-MS) is described.
      Optimization focused on a SPME-GC-MS procedure for determination of 2
      chlorovinylarsonous acid (CVAA), the primary decomposition product of the
      chemical warfare agent known as Lewisite. Two other organoarsenic compounds of
      environmental interest, dimethylarsinic acid and phenylarsonic acid, were also
      studied. A series of dithiol compounds was examined for derivatization of the
      arsenicals, and the best results were obtained either with 1,3-propanedithiol or
      1,2-ethanedithiol. The derivatization procedure, fiber type, and extraction time
      were optimized. For CVAA, calibration curves were linear over three orders of
      magnitude and limits-of-detection were < 6.10(-9) M in solution, the latter a
      more than 400 x improvement compared to conventional solvent extraction GC-MS
      methods. A precision of < 10% R.S.D. was typical for the SPME-GC-MS procedure.
      The method was applied to a series of water samples and soil/sediment extracts,
      as well as to aged soil samples that had been contaminated with Lewisite.

PMID- 9646500
TI  - Cell proliferation in chicken intestinal epithelium occurs both in the crypt and
      along the villus.
AB  - The location of cell proliferation and differentiation in chicken small
      intestinal epithelium was examined using immunostaining, measurement of DNA
      synthesis and brush-border enzyme activities. Chicken enterocytes were removed
      sequentially from the villus using a modification of the Weiser (1973) method.
      Alkaline phosphatase activity was relatively constant along the villus tip-crypt
      axis but decreased in the crypt fractions, whereas sucrase and maltase activities
      showed higher activity in the upper half of the villus and lower activity in the
      lower half of the villus and in the crypt. Immunostaining of proliferating cell
      nuclear antigen indicated the presence of proliferating cells both in the crypt
      and along the villus, including some activity in the upper portion; the crypt
      region exhibited a significantly higher number of proliferating cells. Labelled
      thymidine incorporation into cell fractions after 2 h incubation exhibited a
      similar pattern of proliferation, with the most active region observed in the
      crypt and proliferation activity decreasing along the villus. However, some
      activity was found in the upper half of the villus. After 17 h incubation, cells
      from the middle region of the villi showed greater proliferation ability than the
      2 h incubation. These results indicate that, unlike mammals, chicken enterocyte
      proliferation is not localized only in the crypt region, and that the site of
      enterocyte differentiation is not precisely localized.

PMID- 9646501
TI  - The effects of cortisol and testosterone on renal function in male Antechinus
      stuartii (Marsupialia).
AB  - Seasonal changes in the physiology of Antechinus stuartii result in complete male
      mortality after mating. The most important endocrine changes in males are large
      rises in plasma testosterone and cortisol concentrations. Glomerular filtration
      rate (GFR) in males declines coincident with high plasma testosterone and
      cortisol. In the present study GFRs were measured in males captured in May (when
      endogenous plasma testosterone and cortisol levels are low) and given depot
      injections of either saline, testosterone-only, cortisol-only or testosterone
      plus cortisol at doses designed to mimic plasma levels during the mating period.
      GFR decreased significantly with testosterone injection, independent of cortisol
      treatment. Urinary concentrations of sodium and chloride, and osmolality
      decreased significantly with cortisol treatment, although the addition of
      testosterone reversed the effect. Total urinary excretion of electrolytes was
      similar between groups. Plasma potassium levels significantly increased in
      testosterone plus cortisol treated males. Plasma sodium levels significantly
      increased and plasma chloride significantly decreased in all groups treated with
      cortisol. Water consumption significantly increased in all cortisol-treated males
      and food consumption significantly increased in all testosterone-treated males.
      The seasonal renal functional changes observed in A. stuartii were mimicked by
      testosterone administration.

PMID- 9646502
TI  - Analysis of parotid and mixed saliva in Roe deer (Capreolus capreolus L.).
AB  - In ruminants, different functions have been ascribed to the different salivary
      glands according to the feeding type. In this context, possible adaptations of
      salivary functions were investigated regarding the secretion of various proteins
      by different types of salivary glands. To yield uncontaminated parotid saliva in
      large quantities, a non-surgical method has been developed. Parotid gland
      secretions were collected via endoscopic placement of guide wires into each
      parotid duct, which were subsequently used for placement of collection catheters.
      Salivary flow was stimulated by intra-glandular administration of the
      parasympathomimetic compound pilocarpine-hydrochloride into the parotid gland.
      Mixed saliva (excluding parotid saliva) was collected into sterile tubes by
      normal outflow during the sampling of parotid saliva. The total flow volume, flow
      rate and the content of proteins as well as of several ions (Na+, K+, Ca2+,
      inorganic phosphate) of both types of saliva were measured in sheep, fallow deer
      and roe deer. Roe deer secreted the highest amount of total salivary proteins
      relative to body mass [mg/kg body mass] and the highest relative volume [ml/10
      min/kg body mass], both in parotid and mixed saliva, of all ruminant species
      examined. Additionally, the protein profile and the tannin-binding properties of
      parotid and mixed saliva in roe deer were investigated. Parotid saliva bound
      almost twice as much tannin as mixed saliva, underlining the importance of
      yielding uncontaminated parotid saliva for tannin-binding studies.

PMID- 9646503
TI  - Metabolic suppression in anoxic frog muscle.
AB  - Microcalorimetry is the only direct method for measuring moment-to-moment changes
      in whole-cell metabolism (as heat output) during anoxia. We have adapted this
      methodology, in conjunction with standard muscle isolation techniques, to monitor
      metabolic transitions in isolated frog (Rana temporaria) sartorius muscle during
      anoxia and recovery (reoxygenation). Anoxia (sustained 1 h, following 2 h
      progressive hypoxia) suppressed muscle heat output to 20% of the stable normoxic
      level. This effect was fully reversible upon reoxygenation. Metabolite profiles
      were consistent with other anoxia-tolerant vertebrates--most notably, adenosine
      triphosphate (ATP) content during anoxia and reoxygenation remained unchanged
      from normoxia (pre-anoxic control). In addition, the concentration of K+ ions
      ([K+]) in interstitial dialysates remained stable (2-3 mM) throughout anoxia and
      recovery. Interstitial [lactate-] increased slightly, in accord with anaerobiosis
      supporting suppressed metabolic rates during anoxia. The degree of anoxic
      suppression of metabolism observed is similar to other vertebrate models of
      anoxia tolerance. Furthermore, stable ATP concentrations and interstitial [K+] in
      the isolated tissue suggests that intrinsic mechanisms suppress metabolism in a
      manner that coordinates ATP supply and demand and avoids the severe ion
      imbalances that are characteristics of hypoxia-sensitive systems.

PMID- 9646504
TI  - Behaviors and nutritional importance of coprophagy in captive adult and young
      nutrias (Myocastor coypus).
AB  - To estimate the contribution of coprophagy to protein intake, we observed the
      behavior, particularly that associated with coprophagy, in adult and young
      captive nutrias (experiment 1), and analyzed chemical composition and amino acid
      composition, including diaminopimeric acid (DAP), an indication of bacterial
      deprived protein, of soft feces, entire hard feces, and the black part and green
      part of hard feces (experiment 2). Nutrias practiced coprophagy 48 times per 24 h
      in adults, and 28 times in young animals, which not only had a 24-h rhythm but
      also had 1-h or 2-h short-term rhythms. Nutrias ingested food and drank water
      vigorously after sunset, following which they practiced coprophagy from midnight
      to morning, before lying down for much of the day. When coprophagy was prevented
      we sampled soft feces, produced from midnight to noon, which had high (P < 0.05)
      concentration of crude protein (CP), DAP on a dry matter (DM) basis and 13 amino
      acids on a 16 g N basis than hard feces, and had a low (P < 0.05) content of acid
      detergent fiber (ADF). CP was greater in the black part than the green part of
      hard feces (P < 0.05) although ADF was less (P < 0.05). The chemical composition
      of the black part of hard feces was not significantly different from that of soft
      feces. The dry weight of soft feces excreted in experiment 1 was 34.5 g and 9.7 g
      DM per 24 h in adult and young animals, respectively. Using this value, the
      contribution of soft feces to CP intake in adult nutrias was estimated as 16%,
      superior to that obtained in rabbits for a diet with similar ADF concentration.
      To Met and Lys intake the contribution of soft feces was 26% and 19%,
      respectively in adult animals. These results suggest that coprophagy is quite an
      effective manner for nutrias to ingest extra protein.

PMID- 9646505
TI  - Muscle capillary supply in hind limb and diaphragm of the common shrew (Sorex
      araneus).
AB  - Shrew species of the subfamily Soricinae have unusually high metabolic rates when
      compared to Crocidurinae shrews and other similar-sized mammals. The aim of this
      study was to clarify whether the high basal metabolic rate of Soricinae shrews is
      reflected in a high capillary density in their muscles. To this end, the
      capillary supply of four limb muscles and diaphragm of the common shrew (Sorex
      araneus) was quantified from cross-sectioned muscles. The capillary densities of
      the limb muscles were 2575 +/- 329, 3111 +/- 299, 2812 +/- 197 and 2752 +/- 173
      capillaries mm-2 fibre area in gastrocnemius lateralis, g. medialis, plantaris
      and soleus, respectively. Capillary density of the shrew diaphragm (6691 +/-
      1057) was double that of the limb muscles. This value is among the highest ever
      measured in mammals. In general, the capillary supply in the hind limb of the
      common shrew is about 3-4 times higher than commonly found in the leg muscles of
      the laboratory rat or other bigger mammals, but similar to those in Crocidurinae
      shrews and some small rodents. Thus the high resting metabolism of the common
      shrew is not associated with an extraordinarily high capillary density. The
      apparent disparity between basal metabolic rate and muscle capillary supply in S.
      araneus is probably due to the small aerobic scope of shrews in the subfamily
      Soricinae.

PMID- 9646506
TI  - Characterization of a voltage-dependent conductance in the basolateral membrane
      of leech skin epithelium.
AB  - Voltage clamp studies were performed on the dorsal integument of Hirudo
      medicinalis. Under apical calcium-free conditions an inward-directed component of
      transepithelial current was activated by changes of transepithelial voltage.
      Depolarization caused up to 50% increase of the transepithelial sodium current.
      Hyperpolarization had no comparable effects. With calcium (1.8 mM) or amiloride
      (100 microM) in the apical solution and in sodium-free solutions the inward
      directed current failed to increase after depolarization. Activation also
      occurred under chloride-free conditions. Permeabilization of the apical membrane
      by nystatin (5 microM) increased the current activation significantly. After
      nystatin, calcium as well as amiloride lost their inhibitory effects. This
      indicates a basolateral localization of the voltage-dependent conductance.
      Vesicle insertion or cytoskeletal structures are probably not involved in
      regulation, as seen by the lack of effects of brefeldin A and the cytochalasins B
      and D. However, serosal hyposmolar solutions (170 mosmol.1(-1)) caused a
      reinforced activation of the current. Our results indicate a voltage-dependent
      conductance in a tight sodium-absorbing epithelium.

PMID- 9646507
TI  - Torpor patterns in the pouched mouse (Saccostomus campestris; Rodentia): a model
      animal for unpredictable environments.
AB  - Patterns of spontaneous and induced daily torpor were measured in the
      Afrotropical pouched mouse (77-115 g), Saccostomus campestris, in response to
      photoperiod, temperature, and food deprivation, using temperature telemetry.
      Photoperiod had no influence on the incidence, depth, or duration of daily torpor
      in either males and females. Although the testis size index decreased in response
      to food deprivation and photoperiod by a maximum of 24%, full testis regression
      did not occur. Torpor bout duration was, on average, 5.3 h, independent of
      photoperiod and ambient temperature. Males did not enter torpor in response to
      food deprivation but did in response to low ambient temperature, though
      significantly less frequently than females. At normothermia, the body
      temperatures (daily minimum, mean, maximum) of males were significantly lower
      than those of females. Minimum body temperatures of both males and females during
      torpor did not fall below 20 degrees C at an ambient temperature of 15 degrees C.
      The patterns of torpor measured here differ from those observed in species from
      strongly seasonal environments. They suggest adaptation to an environment
      rendered unpredictable by the El Nino Southern Oscillations. As an aseasonal,
      opportunistic breeder capable of year-round adaptive hypothermia, the pouched
      mouse represents an excellent model animal for research on physiological and
      behavioral adaptations to unpredictable environments.

PMID- 9646508
TI  - The effect of infusion of hypertonic saline on glomerular filtration rate and
      arginine vasotocin, prolactin and aldosterone in the domestic chicken.
AB  - Domestic fowl were infused for 60 min with isotonic saline followed by 90 min
      with hypertonic saline. Plasma electrolyte concentrations, osmolality and
      haematocrit were measured. Urine electrolyte excretion rates, osmolar output and
      urine flow rates were also monitored. From these results fractional excretions of
      electrolytes were calculated. The renal function markers inulin and rho-amino
      hippuric acid were infused to enable the measurement of glomerular filtration
      rate and plasma clearance of rho-amino hippuric acid, respectively. Plasma
      samples were also taken to assay for the hormones prolactin, aldosterone and
      arginine vasotocin. Plasma electrolytes and osmolality, fractional excretion of
      electrolytes and osmolar output all increased, while haematocrit decreased,
      throughout the experiment. However, no significant change was found in urine flow
      rate and little change was seen in glomerular filtration rate. The clearance of
      rho-amino hippuric acid, which provides an indication of renal plasma flow,
      increased during hypertonic saline infusion. Plasma concentrations of aldosterone
      and prolactin decreased during the experiment and plasma concentrations of
      arginine vasotocin increased. Infusion of hypertonic saline had no consistent
      effect on glomerular filtration rate, which may be due to conflicting influences
      of expansion of the extracellular fluid volume and increased plasma osmolality.

PMID- 9646509
TI  - Pulmonary cryptococcosis due to a capsule-deficient strain confused with
      metastatic lung cancer.
AB  - A patient with hepatocellular cancer developed pulmonary cryptococcosis due to
      infection with a capsule-deficient Cryptococcus neoformans. Pulmonary lesions
      initially diagnosed as metastatic cancer by chest x-ray film and CT scan were
      subsequently found to be fungal granulomas by autopsy. Although morphologic
      studies of the fungi were insufficient to render a specific mycologic diagnosis
      because of the absence of encapsulated yeasts, fluorescent antibody studies
      confirmed the diagnosis of cryptococcosis. The use of various stains and electron
      microscopy for the pathological differential diagnosis of cryptococcosis caused
      by capsule-deficient yeasts is discussed.

PMID- 9646510
TI  - Effect of sub-inhibitory concentration of chlorhexidine on lipid and sterol
      composition of Candida albicans.
AB  - The effect of a sub-inhibitory concentration of chlorhexidine on lipid and sterol
      composition of Candida albicans was investigated. The total lipid content of this
      yeast grown in the presence of chlorhexidine was reduced whilst the total sterol
      content was increased compared with control-grown cells. Lipids and sterol
      analyses of this yeast grown in the presence and absence of chlorhexidine are
      presented. Chlorhexidine-grown yeast had a higher level of
      phosphatidylethanolamine, phosphatidylcholine and monogalactosyldiacylglycerol.
      Lower proportions of phosphatidylinositol plus phosphatidylserine, phosphatidic
      acid and cardiolipin were found in C. albicans grown in the presence of the drug
      when compared with control-grown yeast. The major fatty acids in control-grown
      cells were C16 and C18. Drug grown-cells had higher proportions of palmitic acid
      (16:0) and stearic acid (18:0), but lower proportions of palmitoleic acid (16:1)
      and oleic acid (18:1). Chlorhexidine also decreased the unsaturated-to-saturated
      fatty acid ratio, while the C16/C18 ratios increased compared to control-grown
      cells. Differences in the fatty acid composition of major phospholipids and
      neutral lipids between drug and control-grown yeast were also detected. Sterol
      analysis of control-grown cells showed that the major sterol present was
      ergosterol (55.4% wt). A significant increase in ergosterol and obtusifoliol was
      observed in chlorhexidine-treated cells and a significant decrease in squalene
      and lanosterol. Our results suggested that chlorhexidine affected the lipid and
      sterol composition of C. albicans.

PMID- 9646511
TI  - Preserved ascomatal and other fungal structures on the remains of a ninth century
      Longobard abbess exhumed from a monastery in Pavia, Italy.
AB  - Auxarthron californiense, Mixotrichum aeruginosum, Oncocladium flavum and
      Chaetomium elatum were recognized on the basis of ascomatal structures on the
      remains of a Longobard abbess who died in the IX century A.D. These fungi, which
      had remained isolated in a crypt of the S. Felice Monastery of Pavia for almost
      1000 years, are phenotypically identical to the type specimens. The occurrence of
      these fungi and their ecological role are discussed.

PMID- 9646512
TI  - Prevalence of otomycosis in malnourished children in Edo State, Nigeria.
AB  - Out of the total number at 200 suspected cases of otomycoses consisting of 40
      malnourished and 160 apparently healthy children examined in this study between
      the months of July and August in Edo State, 64 Cases (32%) were identified to be
      of fungal aetiology on the basis of positive culture and careful microscopic
      examination. The state at protein energy malnourishment was deterwined using
      physicians' comments in their case files. The fungal agents isolated were
      Aspergillus niger 28 (43.8%); A. fumigatus 4 (25%); Fusarium solari 4 (6.3%);
      Candida albicans 8 (12.5%); and Hendersonula teruloidea types torn B 5 (6.3%). Of
      these isolates, A. niger having an solation rate of (43.8%) was found to be the
      most predominant fungal species associated with otomycosis.

PMID- 9646513
TI  - Experimental candidal mastitis in goats: clinical, haematological, biochemical
      and sequential pathological studies.
AB  - The present study, first of its kind, was conducted with the objectives to
      understand hitherto little known aspects of candidal mastitis, like its
      sequential pathology, pathogenesis and clinico-biochemical changes. For this
      purpose, unilateral intramammary inoculation of 10 goats with Candida albicans
      (1.2 x 10(7) yeast cells) resulted in the development of mastitis, with gross and
      microscopic lesions being restricted to the infected udder halves only and
      without dissemination of infection to the opposite uninfected udder halves as
      well as other organs of the body. The experiment was continued for 40 days and
      after infection, there was sharp fall in milk yield and Candida albicans was
      directly demonstrated in the milk and re-isolated from the milk and udder tissues
      up to 30th day after inoculation. An increase in total immunoglobulins in the
      milk and plasma along with increase in total plasma proteins were also observed.
      Haematology revealed leukocytosis and neutrophilia. Microscopically, there was
      acute purulent mastitis, which later became chronic, nonpurulent and interstitial
      with formation of granulomas. It was concluded that Candida albicans was highly
      pathogenic to the lactating goat mammary gland even without immunosuppression or
      antibiotic treatment, resulting in severe irreversible tissue damage and nearly
      complete agalactia.

PMID- 9646514
TI  - Temporal changes of 210Po in temperate coastal waters.
AB  - The temporal variation of Polonium-210 (210Po) was examined in coastal sea water,
      the mussel Mytilus edulis, the winkle Littorina littorea and green alga Ulva
      lactuca in order to investigate the entry of 210Po into the marine food chain.
      More than 99% of 210Po in the water column occurred in the particulate phase.
      Dissolved 210Po concentrations peaked during the spring phytoplankton bloom and
      it is suggested this is related to preferential scavenging of 210Po by the
      increased numbers of bacteria, viruses and small dissolved particulates. Changes
      in L. littorea 210Po specific activity are thought not to be related to food, but
      to a drop in body weight following spawning. Much of the 210Po accumulated by M.
      edulis was located in the digestive gland. The specific activity of 210Po in the
      digestive gland of M. edulis was shown to be strongly correlated with changes in
      sea water suspended particulate specific activity. Examination of other trace
      metal (Ag, Al, As, Ca, Cd, Cr, Co, Cu, Fe, Hg, K, Mg, Mn, Na, Ni, Sb, Se, Sn and
      Zn) variations in the digestive gland revealed that class B and borderline metals
      had a strong positive correlation with 210Po. On-going work is investigating
      whether the accumulation and loss of 210Po is affected by the presence of
      metallothioneins.

PMID- 9646515
TI  - Trace elements in the Korean coastal environment.
AB  - The present article reports on the results of trace metal analysis in the Korean
      coastal environment during the last decade. Trace metals of Cd, Cu, Pb and Zn in
      seawater, sediments and mussels were determined in coastal areas of East, South
      and Yellow Seas. Clean sampling, the use of ultrapure reagents, reference
      materials and clean-room analysis were carried out to assure quality control. The
      concentrations of trace metals in the Korean coastal environment were compared
      with the results from other parts of the world oceans.

PMID- 9646516
TI  - An overview of trace metal pollution in the coastal waters of Hong Kong.
AB  - The state of metal pollution in Hong Kong's coastal waters has been assessed by
      measuring metal levels in: (i) the water column; (ii) sediments and (iii) in
      organisms, i.e. biomonitors. Current literature is reviewed. Data from sediment
      analysis have shown that metal pollution is most severe in the urban areas of
      Victoria Harbour, Tolo Harbour, Deep Bay and Northwestern waters. Bottom
      sediments in typhoon shelters are particularly heavily polluted with, for
      example, Cu levels from Kowloon Bay reaching 5300 mg.kg-1 in 1995. Since 1987,
      levels of pollution have generally either stabilized or fallen in Deep Bay and
      Victoria Harbour but have increased in Inner Tolo Harbour and Northwestern
      waters. Many biomonitors have been used to study metal pollution in Hong Kong,
      the most popular of which are barnacles, mussels (in particular Perna viridis)
      and algae (in particular Ulva lactuca). Biomonitoring studies generally recorded
      high levels of metal pollution in Victoria Harbour in the late nineteen seventies
      and early eighties, with increasing pollution of the semi-enclosed Tolo Harbour
      through the eighties and early nineties. In a recent study using barnacles, the
      levels of Ag, As, Cd, Cu, Hg, Pb and Zn were shown to be greatly reduced as
      compared to those recorded in 1986 and 1989, respectively. Levels of metal
      pollution in Hong Kong coastal waters may have lowered in the last 10 years.

PMID- 9646517
TI  - Field studies on imposex and organotin accumulation in the rock shell, Thais
      clavigera, from the Seto Inland Sea and the Sanriku region, Japan.
AB  - Field studies on imposex and organotin (butyltin and phenyltin) contamination in
      the Japanese molluscs (the rock shell, Thais clavigera, and the Pacific oyster,
      Crassostrea gigas) were conducted along the coast of both the Seto Inland Sea and
      the Sanriku region, Japan, during February-March 1996. The percentage occurrence
      of imposex in the rock shell, Thais clavigera, was still 100% at all sites
      surveyed (22 and seven sites in the Seto Inland Sea and the Sanriku regions,
      respectively). Observed values of the Relative Penis Length (RPL) index (%),
      defined as the ratio of mean penis length in females to that in males, exceeded
      50 at many sites. Sterile individuals whose oviducts were blocked by vas deferens
      formation were also extensively observed. Tissue concentrations of organotin
      compounds in the rock shell and the Pacific oyster were higher than those from
      other areas of Japan. The degree of imposex (RPL index) was correlated with the
      sum of TBT and TPT concentrations in tissue of the rock shell. Less recovery from
      imposex in the rock shell and less amelioration of TBT pollution were observed,
      suggesting that organotin use in antifouling paints has still continued for
      vessels larger than 25 m in length and that it has influenced imposex symptoms in
      the rock shell.

PMID- 9646518
TI  - Uptake and depuration of 63Ni by Mytilus edulis.
AB  - The uptake and depuration of Ni (as radioisotope 63Ni) by Mytilus edulis
      (Mollusca: Bivalvia) has been investigated in a laboratory mesocosm. Nickel was
      reversibly held on low energy surface sites of estuarine suspended particulate
      matter (SPM), with a partition coefficient of the order 10(3) ml g-1, resulting
      in approximately 80% of radioisotopic Ni being in the dissolved phase. Mussels
      were fed a diet of radio-labelled estuarine SPM for 30 h in a flow-through
      exposure period and for a further 24 h in a static exposure period. Following
      exposure, the mussels were allowed to depurate in particle-free seawater.
      Pseudofaeces and faeces were collected throughout the experiment and tissues were
      dissected after 48 h of depuration. The 63Ni activity in the faeces was
      approximately 50% of that in the feedstock SPM, while the activity in the tissues
      was 2-29% of SPM activity. Tissue-specific accumulation occurred in the order
      viscera > byssus > mantle > adductor muscle > gill > foot. The results are
      discussed in the context of the bioavailability of Ni to mussels.

PMID- 9646519
TI  - Biological monitoring of the impacts of the Ok Tedi copper mine on fish
      populations in the Fly River system, Papua New Guinea.
AB  - Monitoring of the impacts of the Ok Tedi copper mine on fish populations in the
      Fly River system in Papua New Guinea has recorded approx. 100 species of fish
      representing 32 families. Fish catches have shown considerable temporal and
      spatial variability but, since the commencement of mine operations and the input
      of mine-derived waste material into the headwaters of the system, long-term
      monitoring has revealed significant reductions in fish catches at most riverine
      sites in the Ok Tedi, upper and middle Fly River. However, no significant
      declines in fish catches have been recorded in the lower Fly or delta areas.
      Possible mechanisms accounting for the declines in fish catches in the river are
      discussed. Although catches in some floodplain habitats have also declined, these
      changes are thought to be associated with the effects of natural climatic
      phenomena, particularly El Nino droughts. Introduced species and increased
      commercial and artisanal fishing may also have had an effect. Levels of copper,
      zinc, lead and cadmium were found to be elevated in tissues from a range of fish
      species taken from riverine and floodplain sites sampled in the Ok Tedi and Fly
      Rivers. Metal levels were generally much higher in liver and kidney than from
      flesh. There was a general trend for metal concentrations to decrease with
      distance downstream from the mine, suggesting a mine-related effect.
      Significantly higher metal concentrations were recorded at 'impact' compared to
      'control' sites. The intake of dietary copper by humans consuming fish taken from
      the river is well within guidelines set by the World Health Organisation and does
      not constitute a health risk. Ok Tedi Mining Limited has recently initiated a
      programme of mitigation works aimed at reducing the adverse effects of mine
      wastes on the river environment.

PMID- 9646520
TI  - Accumulation of heavy metals in freshwater molluscs.
AB  - Heavy metals in the aquatic environment have to date come mainly from naturally
      occurring geochemical materials. However, this has been enhanced by human
      activity such as gold mining in the case of heavy metal pollution in Sg Sarawak
      Kanan. The high suspended solid loads in the river have quite efficiently removed
      most soluble metals from the water and trapped them in the bottom sediment. Three
      freshwater mollusc species were collected at the point source of the heavy metal
      pollutants and analysed for the heavy metal contents in their tissues and shells.
      Two of the mollusc species (Brotia costula and Melanoides tuberculata) are purely
      freshwater species while the Clithon sp. nr retropictus is able to survive in
      fresh and brackish water environments. The Brotia costula and the Clithon sp. are
      the edible species which are sold in the market. Accumulation of As, Cu, Fe, Se
      and Zn in all the three mollusc species were determined and the level of As in
      the tissues of Brotia costula and the Clithon sp. was much higher than the
      permissible level for human consumption. The mollusc species also demonstrated
      different preferences for the uptake of different metals. Variations in the heavy
      metal contents in the shell and tissues of the same species were also observed.

PMID- 9646521
TI  - Comparison of metallothionein induction in response to cadmium in the gills of
      the bivalve molluscs Mytilus galloprovincialis and Ruditapes decussatus.
AB  - Metal binding characteristics and metallothionein induction differ markedly among
      the gills of the bivalve molluscs Mytilus galloprovincialis and Ruditapes
      decussatus exposed to sublethal cadmium concentrations (100 micrograms/l). The
      rates of cadmium uptake as well as the percentage of cadmium bound to the cytosol
      were significantly higher in the gills of M. galloprovincialis when compared with
      that of R. decussatus. Similarly metallothionein concentration detected in the
      gills of M. galloprovincialis increase fourfold while for the clam R. decussatus
      metallothionein concentrations increased only twofold.

PMID- 9646522
TI  - Haemocyanin and the binding of cadmium and zinc in the haemolymph of the shore
      crab Carcinus maenas (L.).
AB  - The trace metals cadmium and zinc are taken up from solution into haemolymph of
      the shore crab, Carcinus maenas, where they bind to the respiratory pigment
      haemocyanin. Investigations using FPLC and PAGE to separate the constituent
      dodecamer and hexamer aggregations of haemocyanin showed a difference between the
      distribution of cadmium and zinc between the two aggregate states. In the
      haemolymph, labelled cadmium binds not only to haemocyanin but, at least
      initially, it is also associated with low molecular size material or exists as
      free cadmium ions. The binding of cadmium to haemocyanin is not an immediate
      process. Initially the binding of cadmium favours the hexamer; only later is a
      more even distribution between the two aggregate states apparent. Newly taken up
      labelled zinc is rapidly bound to haemocyanin. The majority of both total and
      labelled zinc in the haemolymph is bound to haemocyanin, with the hexamer having
      a greater binding affinity for zinc than the dodecamer. This suggests that
      formation of the dodecamer leads to a blocking of zinc-binding sites and/or that
      the hexamer consists of subunits which possess a relatively high affinity for
      zinc.

PMID- 9646523
TI  - Effects of mercuric chloride and sodium selenite on some immune responses of blue
      gourami, Trichogaster trichopterus (Pallus).
AB  - The immunotoxicological effects of mercuric chloride and sodium selenite on blue
      gourami were studied. Some immune responses ranging from non-specific to specific
      were investigated. These include tissue lysozyme activity, kidney lymphocyte
      proliferation and plasma agglutinating antibody titre against bacteria. After 2
      weeks of chronic exposure, 0.09 mg/l of Hg2+ alone induced a significant increase
      of kidney lysozyme activity of 4196.3 +/- 1171.0 U/g, but it decreased to 1577.4
      +/- 902.4 U/g when exposed simultaneously to equiconcentration of selenium.
      Plasma lysozyme activity was also increased by co-administration of Hg2+ and
      SeO3(2-). The level of plasma agglutinating antibody against Aeromonas hydrophila
      L37 was lowered in the chemical-treated fish. This indicates that the fish
      immunity was impaired by action of mercury and selenium. However, the in vitro
      lymphocyte proliferation test shows that mercury concentration lower than 0.045
      mg/l Hg2+ enhanced the mitotic rate of kidney lymphocytes by approximately 30%. A
      high concentration of mercury caused irreversible damaging effects on con A
      induced lymphoblastogenesis. In contrast, the inhibitory effect of low
      concentrations of mercury could be removed by washing. On the other hand,
      selenium showed a suppressive effect on the lymphocyte proliferation even at 0.5
      mg/l.

PMID- 9646524
TI  - Hong Kong male subfertility links to mercury in human hair and fish.
AB  - The focus of the present study was on the relationship between Hong Kong male
      subfertility and fish consumption. Mercury concentrations found in the hair of
      159 Hong Kong males aged 25-72 (mean age = 37 years) was positively correlated
      with age and was significantly higher in Hong Kong subjects than in European and
      Finnish subjects (1.2 and 2.1 ppm, respectively). Mercury in the hair of 117
      subfertile Hong Kong males (4.5 ppm, P < 0.05) was significantly higher than
      mercury levels found in hair collected from 42 fertile Hong Kong males (3.9 ppm).
      Subfertile males had approx. 40% more mercury in their hair than fertile males of
      similar age. Although there were only 35 female subjects, they had significantly
      lower levels of hair mercury than males in similar age groups. Overall, males had
      mercury levels that were 60% higher than females. Hair samples collected from 16
      vegetarians living in Hong Kong (vegans that had consumed no fish, shellfish or
      meat for at least the last 5 years) had very low levels of mercury. Their mean
      hair mercury concentration was only 0.38 ppm.

PMID- 9646525
TI  - Trace metal pollution in Hong Kong: implications for the health of Hong Kong's
      Indo-Pacific hump-backed dolphins (Sousa chinensis).
AB  - The territorial waters of Hong Kong are highly contaminated with anthropogenic
      pollutants, including trace metals. Hong Kong's population of Indo-Pacific hump
      backed dolphins (Sousa chinensis) inhabits an area where a high volume of sewage
      waste discharge and the close proximity of contaminated mud pits mean a
      considerable potential for trace metal contamination. Trace metal concentrations
      in the muscle tissue of fish caught from areas of high dolphin abundance are
      notable. However, in order to gauge the amount of trace metal consumed by
      dolphins, whole fish must be analysed. Whole fish from areas of high dolphin
      abundance have considerably higher trace metal loads than muscle tissue alone.
      Considering the consumption of prey items by dolphins, a daily intake of trace
      metals was estimated as As, 410-518; Cd, 34-44; Co, 4-5; Cr, 40-50; Cu, 44-56;
      Hg, 51-66; Mo, 22-27; Ni, 19-24; Pb, 320-403; Se, 99-125 and Zn, 388-490
      (microgram kg-1 body wt. per day). Concentrations of arsenic, chromium, lead,
      molybdenum and nickel in dolphin tissues were an order of magnitude lower than in
      prey items, suggesting these elements may be excreted by this species. Mercury
      concentrations in dolphin tissues were, however, an order of magnitude higher
      than in prey items and could be considered potentially health threatening (max:
      906 micrograms kg-1 dry wt.). Hong Kong's Indo-Pacific hump-backed dolphin
      population has a high dietary intake of trace metals which may, especially in the
      case of mercury, be a cause for concern.

PMID- 9646526
TI  - Potential protective effect of calcium carbonate as liming agent against copper
      toxicity in the African tilapia Oreochromis mossambicus.
AB  - The lipid peroxidative effects of copper sulfate singly (4 mg/l CuSO4.5H2O) and
      in combination with calcium carbonate (4 mg/l CuSO4.5H2O + 50 mg/l CaCO3) were
      determined in the liver of the African tilapia Oreochromis mossambicus following
      exposures of the fish to the chemicals for 24, 48, 72, 96 and 168 h. Lipid
      peroxidative effects of the treatment with calcium carbonate (50 mg/l CaCO3) and
      with a known hepatotoxicant, carbon tetrachloride (0.25 ml/l CCl4) were also
      determined. Fish not exposed to any chemical served as negative controls. The
      extent of lipid peroxidation was based on hepatic malondialdehyde (MDA) levels as
      assayed using the thiobarbituric acid reaction test. Results suggested the lipid
      peroxidative property of the copper salt which was associated with the toxic
      nature of the heavy metal, although, this effect was not as potent as that of
      CCl4. Findings also indicated a measure of protection against copper
      hepatotoxicity provided by the addition of calcium carbonate as a liming agent in
      the water.

PMID- 9646527
TI  - Survey of trace elements in household and bottled drinking water samples
      collected in Riyadh, Saudi Arabia.
AB  - Total dissolved beryllium (Be), cadmium (Cd), chromium (Cr), copper (Cu), iron
      (Fe), magnesium (Mg), manganese (Mn), mercury (Hg), nickel (Ni), selenium (Se),
      strontium (Sr), vanadium (V) and zinc (Zn) were measured in the drinking water of
      101 households and 21 samples of retail bottled waters purchased in Riyadh, Saudi
      Arabia to ascertain the water quality for human consumption. The Inductively
      Coupled Plasma Spectrometer (ICP) was used for analysis. First-draw Fe, Mn, Ni
      and Zn concentrations decreased significantly after 10 min of flushing in the
      morning. Cd, Fe, Hg, Ni and Zn in some cases exceeded the guideline limits
      recommended by the EEC and WHO.

PMID- 9646528
TI  - Hydrological studies of schistosomiasis transport in Sichuan Province, China.
AB  - Schistosomiasis is a water-bourne parasitic disease endemic to Sichuan Province
      of China. Long-term studies of infection and disease ecology in catchments in
      Sichuan have been supplemented by detailed hydrometric measurements to produce a
      model of water velocity and flow in an irrigation system. The model provides a
      means of estimating travel times of two infectious stages of the parasite from
      source sites to water contact exposure sites for individuals of both the human
      population and the intermediate vector snail populations. The hydrological
      transport model will be part of an overall model of schistosomiasis transmission
      in the catchments. A GIS system is used to manage spatial data of the drainage
      network, land use, infection sources and population centres. The development of
      the Three Gorges Dam in China will increase marshlands and irrigation in areas
      currently free of schistosomiasis. The potential for the spread of
      schistosomiasis into these new areas is a major concern. Hydrological models can
      be of particular importance in assessing future environmental risk.

PMID- 9646529
TI  - QSAR study of the toxicity of benzoic acids to Vibrio fischeri, Daphnia magna and
      carp.
AB  - The toxicities of benzoic acids to Vibrio fischeri, Daphnia magna and carp were
      measured. The results showed that the toxicity to V. fischeri and Daphnia
      decreased in the order of bromo > chloro > fluoro approximately equal to
      aminobenzoic acids. The toxicity of substituted benzoic acids to carp and Daphnia
      was much lower that to V. fischeri. The results also showed that the toxicity of
      benzoic acids to Daphnia decreased as the pH increased. It is suggested that
      ionized and non-ionized forms have different toxic responses. The non-ionized
      form may play an important role in toxicity because the toxicity of benzoic acids
      to Daphnia greatly decreases as the pH increases. The toxicity of benzoic acids
      to Daphnia may operate through non-polar narcosis, based on the regression
      results between the toxicities and partition coefficients (log P) and apparent
      partition coefficients (log D). However, toxicity cannot be predicted from non
      polar baseline models because the ionized and non-ionized form of benzoic acids
      have different contributions to toxicity. Compared with the single descriptors,
      the prediction of toxicity of the benzoic acids was improved remarkably by using
      log P with pKa and log P with ELUMO. For the toxicity of benzoic acids to V.
      fischeri, it is suggested that the toxic mechanism may be different from the
      mechanism in Daphnia and carp. A probable reason is that V. fischeri is a
      unicellular organism with low lipid content, and hence both ionized and non
      ionized forms of benzoic acids can easily cross the cell membrane and contribute
      to toxicity.

PMID- 9646530
TI  - Are nursery schools and kindergartens safe for our kids? The Hong Kong study.
AB  - Pediatric heavy metal (particularly lead) poisoning is a widespread, yet
      preventable problem in many parts of the world. Interior floor dust is found to
      be one of the major pathways of childhood exposure. However, school and health
      authorities in most countries do not have any stipulations nor guidelines in
      regulating heavy metal contamination in floor dusts in schools. This study
      attempts to examine the level of heavy metal contamination in 53 nursery schools
      and kindergartens in Hong Kong and study its relationship with the environmental
      factors. The results of this study reveal that the arithmetic mean level of lead
      in exterior dust is 280.01 mg/kg, with a minimum level of 48.80 mg/kg and a
      maximum of 2108.31 mg/kg, which is somewhat lower than other studies, such as
      those reported by Chan et al. (Biomed. Environ. Sci. 1989;2:131-140) and Akhter
      and Madany (Water Air Soil Pollut. 1993;66:111-119), but those of the manganese
      (mean = 532.16 mg/kg, range = 102.51-1736.25 mg/kg) and zinc levels (mean =
      2694.23 mg/kg, range = 898.33-9899.85 mg/kg) are much higher. Out of the 10
      districts examined, Kwun Tong and North Point are found to be the most polluted.
      They are older districts with polluting industries and heavy traffic. The results
      of the analysis of variance suggest that the heavy metal particulate may
      originate from the exterior. Auto-vehicles are a likely source. The toxins are
      blown inside through the opened windows. Other factors that may affect the
      content of metal in floor dusts are the time since the school was last painted,
      the age of the housing complex, the condition of the school and the use of vacuum
      cleaners.

PMID- 9646531
TI  - Pesticides in stream water within an agricultural catchment in southern Sweden,
      1990-1996.
AB  - Pesticide loss to stream water was studied in a small agricultural catchment in
      southern Sweden during the period 1990-1996. A total of 38 pesticides were
      detected in water samples, including 30 herbicides, four fungicides, three
      insecticides and one metabolite of one of the herbicides. Concentrations of
      pesticides in stream water were observed throughout the sampling periods. Peak
      concentrations occurred during the spraying seasons and following runoff events.
      Daily average concentrations sometimes varied by one order of magnitude from one
      day to another. Pesticides were also found in water samples as a result of
      incautious actions during handling and application procedures. Concentrations
      were lower at the outlet of the catchment area when the water had passed an open
      part of the stream, compared to concentrations detected in discharge from a
      culvert system upstream. This was largely a result of dilution from groundwater
      intrusion during low-flow periods. Sampling at different sites along the culvert
      demonstrated that the small village situated in the catchment did not contribute
      to pesticide findings in the culvert discharge. Wind drift had little influence
      on stream-water quality. Pesticide application for weed control in farmyards
      resulted in a substantial contribution to the pesticide load in stream water.
      Pesticide were persistent in the discharge throughout the winter and originated
      from both autumn and spring applications, as well as from farmyard application.
      Some autumn applied pesticides prevailed in stream flow during the following
      summer. Total amounts of pesticides lost in stream flow during May-September each
      year varied between 0.5 and 2.8 kg during the 7-year period, corresponding to
      approximately 0.1% of the applied amount. Losses of single pesticides were
      generally less than 0.3% of the applied amount during individual years.
      Pesticides from agricultural applications in the catchment constituted, on
      average, 82% of the total transported amount lost during May-September each year,
      of which 2% was from autumn application the previous year. There was an overall
      correlation between amounts used in the catchment and occurrence in the water
      samples. The total pesticide load in water decreased markedly during the course
      of the investigation, in accordance with decreased amounts applied during spring
      and early summer. The results indicate that concentrations of some pesticides
      entering head-water streams in agricultural areas are close to, and during
      certain time periods even above those levels demonstrated as having an impact on
      the aquatic flora and fauna.

PMID- 9646532
TI  - Trace element reference values in tissues from inhabitants of the European Union.
      X. A study of 13 elements in blood and urine of a United Kingdom population.
AB  - Electrothermal atomic absorption spectrophotometry (ETAAS), inductively coupled
      plasma mass spectrometry (ICP-MS) and neutron activation analysis (NAA) were used
      for the quantitative determination of 13 trace elements in urine and seven trace
      elements in whole blood of healthy unexposed British subjects living in three
      regions of the United Kingdom. Careful control of pre-analytical and analytical
      factors have enabled the results obtained from more than 200 individuals to be
      used in proposing reference intervals for the following elements; Al, As, Cd, Co,
      Cr, Cu, Hg, Mn, Mo, Ni, Pb, Se, Tl in urine, and Cd, Cr, Hg, Mn, Pb, Se and Tl in
      blood.

PMID- 9646533
TI  - Imaging assessment before surgical resection.
AB  - The improvement of preoperative imaging techniques gets hepatic surgery easier
      making it more safer and effective. The authors describe the most common hepatic
      pathologies, benign and malignant, pointing out for each one the principal
      diagnostic appearances achievable with, the several techniques and, collating
      these last between them, they optimize the diagnostic-curative pathways for
      several pathologies. Beyond allowing the diagnosis of the lesion's nature, an
      important role of the imaging modalities is also to evaluate the resectability of
      single lesion, weighing up its exact location and the impact on the vascular
      system esteeming, finally, the volume of remnant liver in case of larger
      resections. The intra- and extrahepatic, preoperative staging, of the varied
      hepatic lesions, primitive and secondary, performed comparing the most modern
      diagnostics techniques, results to be dramatically important arterial portography
      during, CT (CTAP), contrast-enhanced helical CT, MR imaging. For each patient
      it's possible to plan the most adequate treatment to his pathology.

PMID- 9646534
TI  - Preoperative portal embolization.
AB  - Excess parenchymal loss associated with hepatectomy is the leading risk
      factor/for liver failure especially in patients with impaired hepatic function.
      Selective portal embolization (PE) before hepatectomy is aimed to induce an
      atrophy of the embolized lobe to be resected, with a compensatory hypertrophy of
      the/counterlobe to be preserved. We performed PE followed by hepatectomy in 58
      patients with hepatocellular carcinoma (HCC, n. = 44) or metastatic liver tumour
      (MLT, n. = 14). All the patients well tolerated PE, and hepatic functional data
      returned to the baseline levels within a week. The left lobe volume increased by
      about 10% after the right PE. Hepatectomy procedures undertaken comprised right
      or extended right lobectomy (n. = 39), central bisegmentectomy (n. = 3), extended
      segmentectomy (n. = 12), and limited resection (n. = 4). The 25 of HCC patients
      underwent right-sided lobectomy despite a presence of hepatic functional
      impairment, and the 3 of MLT patients under went right lobectomy with additional
      resection of the left lobe. As a whole, the operative morbidity and mortality
      rates were 15.5% and 1.7%, respectively (one patient died of liver failure). The
      5-year over all survival rates were 46.8% in HCC patients and 38.0% in MLT
      patients, respectively. Preoperative PE therefore can be an ancillary procedure
      for patients, despite with hepatic dysfunction or with bilobar tumours, who may
      need extensive hepatectomy.

PMID- 9646535
TI  - Clinical application of ultrasonography in liver surgery.
AB  - Modern liver surgery is based upon deep knowledge of the surgical anatomy of the
      liver and improvements with ultrasounds imaging techniques have provided
      multidimensional interpretations of the liver anatomy intraoperatively. The
      technical advances with real-time scanning combined with the pioneering efforts
      of the Japanese liver surgeons have permitted the dynamic adaptation of the
      functional liver anatomy to the real anatomy, thus intimately aiding in segment
      oriented anatomical resection. Intraoperative ultrasound afford several
      advantages such as viewing the internal anatomy in direct relationship to the
      surface landmarks under the probe, enabling higher frequencies resulting in
      greater image resolution. The utilization of intraoperative ultrasound can modify
      the tactics involved with resection of both primary and metastatic liver tumours.
      The routine use of intraoperative ultrasound is strongly advocated since more
      complex procedures can be performed safely since the surgeon proceeds with
      complete knowledge of the real liver anatomy when deciding the feasibility and
      extent of liver resection.

PMID- 9646536
TI  - Hepatic resection: perioperative course and management.
AB  - Normal liver can tolerate even a right trisegmentectomy with caudate resection
      which results' in a reduction of liver volume by 80%, while a decompensated
      cirrhotic liver cannot tolerate even partial hepatic resection. This can be
      ascribed to decreased functional volume and the deterioration of individual
      hepatocyte function, which is caused and amplified by inappropriate
      intraoperative procedures and postoperative management. Problems related to liver
      diseases, including liver cirrhosis, jaundice and chronic active hepatitis,
      operative techniques and postoperative management should be considered during
      hepatic resection. Pathophysiology and tactics for handling these problems will
      be described.

PMID- 9646537
TI  - Vascular occlusion techniques for liver resections.
AB  - Prevention of intraoperative blood loss during liver resection is of prime
      concern. Intraoperative blood loss has indeed repeatedly been shown to adversely
      influence the short-term prognosis of patients undergoing liver resection. There
      is in addition evidence that it could be associated with an increased risk; of
      recurrence in patients operated for an hepato-biliary malignancy through
      impairment of the patient's immune response. The prime concern of the hepato
      biliary surgeon is to minimize blood loss through the control of the major
      vascular structures this may be achieved in several ways that range from
      segmental portal control to total hepatic vascular occlusion. The type of
      vascular occlusion should be selected according to the indication and in
      particular location of the tumour and presence of an associated underlying liver
      disease, the patient's cardiovascular status and the experience of the operator.
      Aim of the authors is to describe the various types of vascular control as well
      as their benefits and drawbacks so as to use the most appropriate technique
      according, to each patient' requirements.

PMID- 9646538
TI  - Repeated hepatectomy for colorectal metastasis.
AB  - Between January 1981 and December 1995, 12 patients, who previously underwent
      hepatic resection for colorectal metastases, were selected for a second liver
      resection for isolated liver recurrence. Mean interval between first and second
      resection was 16 months. Eight patients had solitary and 4 multiple metastasis.
      Two major hepatectomies and 11 wedge resections were performed. Mean follow-up
      was 37 months. No mortality and 33% morbidity was observed. Three and 5-year
      actuarial survival rates were 71% and 42%, while disease-free survival was 30%.
      No patient, primary tumour, or metastases' characteristics were significantly
      associated to survival. Surgical resection is the only therapy that could offer
      reasonable chance of long term survival and, in selected case, of cure. A careful
      patients' selection as well as an accurate surgical technique are essential to
      reduce post operative mortality and morbidity.

PMID- 9646539
TI  - Hepatic resective surgery in cirrhotic patients. Techniques and results of
      anatomical segmentectomies.
AB  - The paper describes the technique of anatomical liver segmentectomies based on
      the extraparenchymal clamping, at the hepatic hilum, of the afferent vascular
      pedicles. The resection is started on the liver surface along the demarcation
      line caused by the ischemia. During parenchymal transection the technique of
      hemihepatic vascular occlusion has been undertaken. The results obtained with 125
      segmentary hepatic resections performed for hepatocellular carcinoma arised on
      cirrhosis are also reported. The overall operative mortality has been 6.4%. The
      actuarial 1 and 3 year survivals were 93.3% and 70.4% respectively. Hepatic
      segmentary resections are recommended for limited hepatic lesions, mainly in well
      compensated cirrhotic patients.

PMID- 9646540
TI  - Hepatic resections through the laparoscopic approach.
AB  - Hepatic surgery has been undergoing progressive modifications in surgical
      approach to liver, passing through tohraco-phrenolaparotomy to bilateral
      subcostal incision and current Makuuchi's. Laparoscopic liver surgery should not
      be considered a new surgery, but simply a new surgical approach, with
      difficulties but advantages too. Laparoscopic hepatic resections are feasible
      with low morbidity and mortality; the short and medium term results are
      comparable to those obtained with open surgery provided that the surgeon has a
      significant experience in open hepatic surgery, advanced laparoscopic surgery and
      the availability of all and pertinent instrumentation. The aim of this paper is
      to show the rationales formal of hepatic resections through the laparoscopic
      approach, focusing on the necessary instrumentation, the surgical technique and
      results.

PMID- 9646541
TI  - [Cervical neurinomas. (Considerations in five cases operated in Day-Surgery)].
AB  - We report the experiment of five cases of neurinoma observed in the division of
      Day Surgery of the Third Surgery Clinic, operating in the Hematology Institute of
      University of Studies "La Sapienza" in Rome. The problems of the diagnosis of
      this neoplasia has been faced, though it is commonly unknown or confused with
      other cervical especially lymphonodules tumefactions, from which it is almost
      impossible to distinguish before the operation. In the period of six years on 775
      cases of cervical neoformations have been operated only 5 patients bearers of
      neuromi; two originated from vago cervicale (right and left), one from simpatico
      cervicale on the left, another from the left spinal accessory and the last from
      the secondary medial trunk of the left brachial plexus. All the patients have
      been operated in Day-Surgery anaesthesia, locoregional and with calming of
      spontaneous breath. One case, that originated from the secondary medial trunk of
      the left brachial plexus, has been operated with microsurgical technique. On all
      the cases has been done a subcapsular exeresis to preserve nervous continuity. No
      post operating complications have been recorded; all the patients discharged in
      the evening. The diagnosis about the nature is left to the final histological
      test on the operating piece. The surgical removal remains even today the elective
      treatment able to exclude probable relapses and potential malignant
      transformation of these tumours.

PMID- 9646542
TI  - [Acute abdominal pain in emergency surgery. Clinical epidemiologic study of 450
      patients].
AB  - A retrospective study on 450 patients admitted in emergency with acute abdominal
      pain in a general surgical unit of the Ist Institute of Surgery of the University
      of Rome "La Sapienza" was carried out during a 7 years period. The aim of the
      study was to identify the most frequent causes of acute abdominal pain correlated
      with age, sex, onset of pain and other conditions in order to improve diagnosis
      and reduce mobility for mortality. Appendicitis was the most frequent diagnosis
      (75 pts = 16.4%). Non-specific abdominal pain (NSAP), found in 71 pts (15.5%),
      cholelithiasis in 57 pts (12.5%), abdominal malignancy in 47 pts (10.3%) were
      other frequent conditions. The largest number of admissions occurred in the age
      groups 60-70 years (16.6%) and 20-30 years (14.2%). Surgical operations were
      performed in 206 patients (45.7%). The overall mortality was 4.2% (19/450 pts)
      and the rate increased significantly in patients aged > 60 years. Postoperative
      mortality was 5.8% (12/206 pts) while mortality rate in non-operated patients was
      2.8%. The causes of perioperative death included perforated peptic ulcer,
      abdominal malignancies (15.4%) and urgent colonic resections (9.4%). The duration
      of inpatients stay increased significantly with the age of the patients,
      including those with nsap. The results of the study indicate a need to review the
      methods of diagnosis of appendicitis and to obtain a better clinical performance
      in patients with nsap.

PMID- 9646543
TI  - [Surgical techniques in ruptured abdominal aortic aneurysm].
AB  - In recent years we are observing an increasing number of authors. The surgical
      results, in the elective cases, are improved drammatically, and now, in many
      Centers, the mortality rate is less than 5%. We haven't observed the same
      improvements for the emergency cases. In this setting the mortality rate is still
      around 50% or more. What we are facing, however, is the changing of the clinical
      picture of this patients. In the most part of cases, the patient dies in the
      Intensive Care Unit, after a long and complex post-operative course, and not more
      in the Operating Room. Still, this could be considered a good result, expression
      of a better surgical experience. The way to obtain higher survival, at the
      moment, is linked to a better understanding of the physiologic derangements in
      the Intensive Care Unit. The authors discuss the organizative and technical
      changes the permitted to achieve this results.

PMID- 9646544
TI  - [Short bowel syndrome: etiologic, pathogenetic aspects and principles of
      treatment].
AB  - A significant problem in surgery following massive intestinal resection is the
      short bowel syndrome characterized by severe fluid and electrolyte loss, watery
      diarrhoea and malnutrition. Total parenteral nutrition and enteral nutrition are
      essential in the clinical course of the syndrome; their use for prolonged periods
      results in the gradual intestinal adaptation and greater absorptive and reservoir
      capacities of the intestinal remnant. Adjunctive surgery can slow rapid
      intestinal transit and induce growth of neo-small-bowel mucosa but is not
      recommended for routine use. The early results of intestinal transplantation in
      the treatment of short bowel syndrome are encouraging. Furthermore chronic
      rejection and systemic sepsis with failure of the graft must be considered and
      indicate that at present this procedure cannot be offered to every patient but
      will be a potential form of therapy in future.

PMID- 9646545
TI  - [Reoperations in surgical oncology: recurrence of colon carcinoma after surgery].
AB  - Colon cancer is the second leading cause of death for cancer disease, after lung
      cancer, with nearly 18,000 deaths per year in Italy. In spite of the progress
      that have taken place over the past 30 years, little improvement has been gained
      in this dismal outcome, and the 5-year survival remains around 50%. Over one half
      of the patients will suffer from recurrence after a potentially curative
      resection. A major challenge lies in better detection of recurrences in order to
      diagnose those patients still amenable to curative resection. Locoregional
      recurrence is of particular interest and its frequency, diagnostic limitations
      and surgical treatment are herein discussed.

PMID- 9646546
TI  - [Morbidity after video-laparoscopic cholecystectomy in cholelithiasis associated
      with liver cirrhosis. A case-control study].
AB  - At present laparoscopic cholecystectomy represents the treatment of choice for
      symptomatic cholelithiasis. Authors performed a retrospective case-control study
      to evaluate whether cirrhosis associated with cholelithiasis increases the risk
      for morbidity of laparoscopic cholecystectomy. Twenty-one patients with
      cholelithiasis and cirrhosis (Child-Pugh class A or B) (group A) and 21 controls
      with cholelithiasis without cirrhosis (group B) entered the study. Controls were
      paired with cases for age, sex, and indication for cholecystectomy (simple
      cholelithiasis, acute cholecystitis). The two groups were compared for rate of
      conversion to open cholecystectomy (19% group A vs 9.5% group B; p = 0.31),
      morbidity (29.5% group A vs 5.3% group B; p = 0.17), median length of surgery (80
      m in the two groups), and median time of postoperative hospitalization (5 days
      group A vs 3 days group B; p = 0.21). No difference among variables resulted to
      be statistically significant. Besides, neither common bile duct injuries nor
      intra or postoperative hemorrhages occurred in patients with cirrhosis. Authors
      conclude that the laparoscopic cholecystectomy can be considered a safe and
      effective surgical procedure also for patients with cholelithiasis associated
      with cirrhosis with a good residual hepatic function.

PMID- 9646547
TI  - [Leiomyosarcoma of the small intestines: case reports].
AB  - Intestinal malignant neoplasms are extremely rare (1% of all solid tumours) and
      leiomyosarcomas represent 20% of them. The authors report the experience of 5
      cases (M:F ratio = 0.6), aged 30-69 yrs old, treated in the period 1985-95. The
      best results have been obtained in 2 cases, characterized by low grading and
      submitted to curative resections. The others presented local and distant (mostly
      hepatic) extensions with a poorer prognosis (1-3 yrs. survival). Leiomyosarcomas
      are particularly binding because of their rarity and aspecific symptomatology,
      determining late diagnosis in most cases. The clinical course, the surgical and
      complementary management, the istology and the prognosis have been analysed.
      Nowadays 5 yrs-survival is very low and the prognosis remains severe because of
      local and distant metastases, already present at laparotomy. New chances may come
      out from better diagnostic techniques and from new complementary
      chemotherapeutical associations.

PMID- 9646548
TI  - [Laparoscopic treatment of biliary cysts].
AB  - Here comes presented three cases of biliary cysts treated with laparoscopic
      technique. In the first case the discovery of a single cyst of small size on the
      hepatic margin have consented the total removal. In the second case was about a
      voluminous unique cyst, while in the third has been found an hepatic
      polycystosis. In both of them has been applied Lin's procedure with
      videolaparoscopic technique.

PMID- 9646549
TI  - [Laparoscopy in iatrogenic lesions of the colon during operative endoscopy].
AB  - Colonscopy is a standard diagnostic and therapeutic procedure that has its own
      morbidity. Colonic perforation is the dangerous complication of this procedure.
      Successful management of perforation by conservative or surgical treatment
      remains controversial. We report two cases, recently observed, of patients with
      colonic perforation occurring during therapeutic colonscopy treated with
      minimally invasive technique.

PMID- 9646550
TI  - Further studies on Trypanosoma mukasai HOARE, 1932 and its biological vector
      Batracobdelloides tricarinata (BLANCHARD, 1897).
AB  - Trypanosoma mukasai from the blood of Clarias lazera was successfully transmitted
      to eight fresh water fish species using B. tricarinata as vector. Such cross
      transmission showed that the trypanosome was not host specific. Previously
      described fish trypanosome species were morphologically indistinguishable, and on
      the basis of the present result they were regarded as a single species, T.
      mukasai. Trypanosomes increased in size the longer they remained in fishes and
      they were observed for up to 7 months in surviving fishes. In B. tricarinata,
      they survived over a period of 10 months involving 18 meals after the initial
      blood meal, provided the fasting period did not exceed 28-80 days. Survival was
      attributed to residual stages in the crop. The population ecology of B.
      tricarinata revealed an increase of the total population and of brooding of eggs
      and/or youngs during spring and summer. Although, the leech fed on a broad
      spectrum of hosts, certain fishes such as Chrysichthys auratus were preferred.
      Also, certain sites (e.g. the head in C. auratus) were preferred to others. The
      amount of blood ingested varied from two to about three times its body weight.
      Time for digestion of blood was dependent on the size of the leech as well as the
      species of the fish. The histopathological changes at the attachment sites of
      leeches were studied.

PMID- 9646551
TI  - [Urinary calculi in small and other animals--a retrospective study of the years
      1980-1989].
AB  - More than 500 uroliths from dogs, cats, minks, rabbits and 9 further animal
      species originating from various regions of former East Germany were analysed.
      The observations were made between 1980 and 1989 using X-ray diffraction and
      infrared spectroscopy. The urinary stones consisted of struvite, whewellite,
      weddellite, cystine, ammonium urate, brushite, whitlockite, hydroxyapatite or
      carbonate-apatite, calcium carbonate, silicon dioxide and organic matrix stones.
      In dogs, the most frequent types were struvite and apatite concrements, followed
      by calcium oxalate and cystine uroliths. Among the diseased animals poodles,
      dachshunds and terriers ranked first. In the analysed material from cats apatite
      and struvite predominated. With few exceptions, minks formed struvite uroliths
      only. The analysed calculi from rabbits consisted principally of calcium
      phosphate or calcium carbonate concrements. The present analysis has been
      compared with results of former studies, differences are discussed.

PMID- 9646552
TI  - Adjuvant properties of killed Propionibacterium avidum KP-40 in vaccination of
      dogs against canine parvovirosis.
AB  - Immunomodulating and adjuvant properties of Propionibacterium avidum KP-40 (PA),
      a potent stimulator of the macrophage-monocyte system and inducer of endogenous
      interferon, were tested in healthy dogs and in dogs vaccinated against canine
      parvovirosis (CPV). A single subcutaneous injection of PA (0.5 mg/kg b. m.) was
      administered either 10 days before or simultaneously with CPV immunization. The
      immunomodulating properties of PA were expressed by enhancement of phagocytic and
      bactericidal activities of blood leukocytes, accompanied by elevated serum levels
      of interferon-gamma and interleukin-1 and higher Con-A-induced transformation
      rates of lymphocytes. Titres of CPV antibodies were significantly (p < 0.01)
      higher in dogs vaccinated and treated with PA either 10 days prior to or
      simultaneously with immunization. It is concluded that PA may be applied as a
      potent and safe adjuvant in vaccination of small animals and additionally, it
      provides enhancement of non-specific antibacterial and antiviral resistance of
      the organism.

PMID- 9646553
TI  - Uterine androgen receptor mRNA expression in metestrous and anestrous bitches
      being healthy or suffering from Pyometra.
AB  - The importance of androgens for the female reproductive system has been
      investigated for decades and a number of androgen sensitive processes has now
      been identified in female reproductive organs. For carnivore species no data were
      available so far about uterine androgen sensitivity and its regulation. The
      present study therefore aimed to investigate whether androgen receptors (AR) are
      present in the dog uterus, whether they are regulated throughout the ovarian
      cycle and whether pyometra affects their expression rate. Uterine tissue samples
      were collected from 28 bitches of different ages and various breeds. The samples
      were grouped according to the stage of estrous cycle (metestrus ME or anestrus
      AE) and the pathological status of the uterus (i.e. suffering from pyometra or
      not). Androgen receptor mRNA (AR mRNA) was quantified from 500 ng of total RNA
      isolated from the tissue samples using an internally standardized reverse
      transcription polymerase chain reaction (RT-PCR) described previously. The amount
      of total RNA extractable per g tissue was elevated during pyometra. The
      successful amplification of the expected 172 bp fragment from canine uterine RNA
      together with the confirmation of the identity of this fragment by sequence
      analysis, demonstrates that AR is expressed in this particular tissue. Comparing
      the expression rates in uteri from bitches during ME or AE being healthy (H) or
      suffering from pyometra (P), the only significant (p < 0.01) difference was found
      between H and P uteri during ME with 3.5-fold lower expression rates in P.
      Although the same seems true for AE bitches, a significant difference could not
      be demonstrated due to the low number (n = 2) of diseased animals in the AE
      group. There was no evident effect of the stage of ovarian cycle on uterine AR
      mRNA levels.

PMID- 9646554
TI  - Alterations in peripheral blood leukocytes functions during enzootic
      bronchopneumonia of calves. Effect of treatment with antibiotics and
      immunomodulators.
AB  - Twelve calves from over veal calf farm were divided into two groups: group I-6
      calves which developed typical signs of enzootic bronchopneumonia and group II-6
      calves with no symptoms of the disease. Both groups of calves were compared with
      respect to changes in several hematological parameters. Some functions of
      peripheral blood leukocytes as random migration, phagocytic index, percent of
      phagocytic cells and percent of NBT positive cells were also scored. In addition,
      changes in serum levels of interferon (IFN) and tumor necrosis factor (TNF) and
      the ability of peripheral blood leukocytes (PBL) to produce IFN and TNF were
      quantitated by biological methods. On the day of diagnosis, in group I of calves
      a significant increase in the total serum protein concentration, hemoglobin
      content, red and white blood cells counts in comparison to control calves (group
      II) was observed. The increased number of NBT positive neutrophils and moderate
      levels of serum IFN and TNF correlated with elevated body temperature, breathing
      and heart rates. Calves with bronchopneumonia (group I) after diagnosis of the
      disease were treated with Tylbian (tylosine derivative), Flumetazon
      (glucocorticoid), Emulselvet (immunomodulator), bromhexinum and sulphonamides.
      Seven days after the beginning of treatment with medicaments a significant
      improvement in clinical symptoms was observed, however, the ability of PBL to
      cytokine production increased significantly 2 weeks after beginning of treatment
      and correlated with significant increase in random migration of neutrophils and
      their phagocytic activity, measured by the percent of phagocytic cells.
      Unexpectedly, in control calves (group II), not exhibiting any symptoms of
      bronchopneumonia at the beginning of experiment, high serum IFN titers were
      detected which decreased significantly during the first week of observation. In
      contrast to that the ability of PBL of control calves to produce IFN increased
      significantly within 3 weeks of observation. The correlations between the ability
      of PBL to produce cytokine and the development of clinical symptoms of
      bronchopneumonia are discussed.

PMID- 9646555
TI  - Colonization capability of orally administered Lactobacillus strains in the gut
      of gnotobiotic piglets.
AB  - In the present study, the effect of Lactobacillus casei subsp. casei and
      Lactobacillus fermentum inoculation on jejunum and ileum colonization in
      gnotobiotic piglets has been observed. The characteristic features of the strains
      used were strong adherence to pig epithelial gut cells as well as inhibitory
      activity against enteropathogenic E. coli under in vitro conditions. Strains were
      inoculated to 2, 3, and 4 day old gnotobiotic piglets at a dose of 2 ml (1 x
      10(8) germs/ml). On the second day after the last inoculation, Lactobacillus
      casei subsp. casei strain counts adhered to the jejunum mucosa and those adhered
      to the ileum mucosa were 4.54 log 10.cm-2 and 5.40 log 10.cm-2, respectively.
      Lactobacillus fermentum counts adhered to the jejunum mucosa and those adhered to
      the ileum mucosa were 5.73 log 10.cm-2 and 4.01 log 10.cm-2, respectively. On day
      5 after the last inoculation, the counts in both strains were by one log higher.
      The results obtained point out to the fact that Lactobacillus casei subsp. casei
      and Lactobacillus fermentum colonized the mucosa of both jejunum and ileum and
      survived in the intestinal tract. The adherence of lactobacilli to gut cells in
      vitro correlated with their capability to adhere to the mucosa of both jejunum
      and ileum in vivo.

PMID- 9646556
TI  - [Clinical-virologic course after superinfection of persistently infected cattle
      with cytopathogenic bovine viral diarrhea virus strains].
AB  - Vaccination with live cytopathogenic (cp) bovine viral diarrhoea virus (BVDV) is
      often used for control of this disease. In animals which are persistently
      infected with noncytopathogenic (ncp) BVDV this can lead to the outbreak of
      mucosal disease (MD). To simulate vaccination of such animals and to monitor the
      clinical-virological course after superinfection, nine clinically healthy calves
      which were persistently viremic were superinfected with different cp BVDV
      strains. One animal succumbed to early onset MD within three weeks after
      superinfection. During the observation period of 18 months four animals developed
      severe clinical signs. While two animals developed late onset MD, the other two
      had to be euthanized due to clinical signs which could not be related to the
      superinfecting BVDV. These results indicated that after superinfection or
      vaccination of persistently infected calves with cp BVDV the probability of
      developing early and/or late onset MD is significantly increased. The risks
      arising from uncritical vaccination of herds with unknown virological status in
      relation with the control of BVDV conforming to the actual official guidelines
      are discussed.

PMID- 9646557
TI  - [Group B Streptococcus infections: new forms. New preventive measures].

PMID- 9646558
TI  - [Seroprevalence versus Parvovirus B19 in blood donors].
AB  - BACKGROUND: The aim of the study was to describe the seroprevalence against
      Parvovirus B19 in a random sample of blood donors in the Hospital Universitario
      de Salamanca. METHODS: We studied the presence of IgG and IgM antibodies against
      Parvovirus B19 in 136 sera from asymptomatic blood donors by enzyme immunoassay
      methods. RESULTS: From 136 samples tested, 88 (64.7%) had positive absorbance
      values for IgG. Forty eight samples (35.5%) were negative. IgM was negative in
      all cases. We did not find indeterminate results. DISCUSSION: Parvovirus
      primoinfection usually happens in the childhood. Thus, we can expect a high
      percentage of general population to have antibodies against Parvovirus B19. Anti
      Parvovirus B19 antibodies prevalence in blood donors was 64.7%. This failure is
      similar to data reported before (65%). Clinical importance of these viruses in
      currently related with hemathopoyesis diseases and with the possible role in
      theratogenesis. The presence of IgG seems to give protection except in some
      chronic infections recently described.

PMID- 9646559
TI  - [Cytomegalovirus: comparative study of diagnostic techniques].
AB  - BACKGROUND: The aim of this study was to undertake a comparative study of a
      series of diagnostic techniques of active infection by cytomegalovirus (CMV) in
      blood (isolation of CMV by shell vial, detection of specific anti-CMV IgG and
      IgM, antigenemia-detection of pp65 antigen by staining with peroxidase- and two
      variants of qualitative polymerase chain reaction [PCR]-conventional PCR or in
      one step and nested PCR-for detection of viral DNA). METHODS: Fifty kidney
      transplant patients were followed for the first 6 post transplant months. All
      except 6 were seropositive for CMV prior to transplantation and only one
      seronegative patient had a seronegative donor. RESULTS: A total of 750 blood
      samples were analyzed, 8 of which were positive by shell vial, 91 by specific IgM
      detection, 115 by antigenemia, 225 for conventional PCR and 440 for nested PCR.
      No positive sample was detected throughout follow up by any of the techniques
      used in only 4 patients (one being the seronegative receptor with a seronegative
      donor). CONCLUSIONS: Antigenemia was found to be the fastest, cheapest and
      simplest method of diagnosing CMV, presenting the advantage of providing
      quantitative results which allow the establishment of a relationship with the
      appearance of symptomatic infections. With the two variants used qualitative PCR
      was observed to be the earliest and most sensitive technique, while being the
      most difficult and the most expensive, with the disadvantage that its great
      sensitivity limits its clinical usefulness.

PMID- 9646560
TI  - [Prevalence of human immunodeficiency virus infection in drug addicts assisted
      from 1991 to 1996 at a detoxification center in Castilla y Leon].
AB  - BACKGROUND: The Word Health Organization (WHO) has recommended epidemiologic
      surveillance of infection by the human immunodeficiency virus (HIV) in high risk
      populations. An important decrease has recently been observed in the prevalence
      of HIV infection in drug addicts in different regions in Spain with notable
      differences being found. The evolution of the prevalence of HIV infection in
      intravenous drug addicts initiating detoxication in Castilla and Leon was
      analyzed. METHODS: Six hundred forty-seven drug addicts (535 males and 112
      females) were studied over 6 years (1991-1996) analyzing HIV seropositivity,
      demographic variables, drug use, age of initiation in drug consumption and route
      used. RESULTS: Most of the drug addicts were males (83%) with a mean age of
      initiation in the use of drugs of 19.6 years. Heroine was most frequently
      consumed in 95% of the patients. The mean length of consumption on admission was
      8.6 years with no significant differences being observed in sexes. A relationship
      was observed between HIV infection and the lower age of initiation in drug usage
      with the greater the age of admission to detoxication the longer the time having
      consumed drugs. The prevalence of HIV infection significantly decreased in males
      and females from 36.8% in 1991 to 17.4% in 1996 (p < 0.0005), with this decrease
      being related to the change from the intravenous to the smoked route of drug
      intake. On multivariate analysis by logistic regression the odds ratio at one
      year of admission was significant (OR = 0.80), years of drug addiction (OR =
      1.15), intravenous route (OR = 3.04) and female sex (OR = 2.75). CONCLUSIONS: A
      significant decrease has been observed in the prevalence of HIV infection in drug
      addicts in Castilla and Leon attending a therapeutic center for detoxication from
      1991-1996.

PMID- 9646561
TI  - [Chronic necrotizing pulmonary aspergillosis: infrequent form of aspergillosis].
AB  - BACKGROUND: Chronic necrotizing pulmonary aspergillosis (CNPA) is a chronic
      pulmonary infection caused by the genus Aspergillus, which usually involves
      moderately immunosuppressed patients. METHOD: We describe 3 patients with a toxic
      syndrome that had lasted several weeks or months, with lung infiltrates in the
      chest X-ray and the CT scan. Mycobacterium tuberculosis could not be isolated
      from different respiratory smears (sputum, bronchoaspiration, Barlett catheter
      and pulmonary punction in the third case). Moreover, there was no response to
      anaerobic treatment. RESULTS: All 3 patients were moderately immunosuppressed (2
      men were COPD and the woman was an asthmatic patient). One of the men was being
      treated for a nocardiosis. In all three cases, A. fumigatus was isolated from de
      different respiratory smears. CONCLUSIONS: To diagnose a CPNA, a high degree of
      clinical suspicion is needed. The differential diagnose should be done with
      pulmonary tuberculosis and anaerobic infections. The presence of a member of the
      genus Aspergillus in the tracheobronchial secretions of a patient should not be
      systematically considered a saprofit, specially when other microorganisms can not
      be isolated.

PMID- 9646562
TI  - [Methods for evaluating diagnostic tests in Enfermedades Infecciosas y
      Microbiologia Clinica].
AB  - BACKGROUND: In the field of infectious diseases and clinical microbiology, the
      evaluation of diagnostic tests (DT) is an important research area. The specific
      difficulties of this type of research has motivated that have not caught the
      severity methodological of others areas of clinical research. This article try to
      asses and characterize the methodology of articles about DT published in
      Enfermedades Infecciosas y Microbiologia Clinica (EIMC) journal. METHODS: Forty
      five articles was selected in the EIMC journal during the 1990-1996 period,
      because of determinate the sensitivity and specificity of different DT.
      Methodological standards, extensively accepted was used. RESULTS: In all of
      articles, except one (98%) the gold standard was specified yours use, however in
      4 studies (9%) include the DT in the gold standard (incorporation bias). The
      correct description of DT was reported in 75% of cases, but only in 11% cases the
      reproducibility of test was evaluated. The description of source of reference
      population, standard of inclusion and spectrum of composition was described in
      58, 33 and 40% of articles, respectively. In 33% of studies presented workup
      bias, only 6% commented blind-analysis of results, and 11% presented
      indeterminate test results. Half of the studies reported test indexes for
      clinical subgroups, only one article (2%) provided numerical precision for test
      indexes, and only 7% reported receiver operating characteristics curves.
      CONCLUSIONS: The methodological quality of DT research in the EIMC journal may
      improve in different aspects of design and presentation of results.

PMID- 9646563
TI  - [Assessment of 4 commercial immunoenzymatic assays for the serologic diagnosis of
      Helicobacter pylori infection].
AB  - BACKGROUND: The aim of this study was to evaluate four commercial tests for the
      serologic diagnosis of infection by Helicobacter pylori based on the detection of
      IgG class antibodies versus this microorganism. METHODS: Four commercial kits
      were analyzed based on the ELISA method in serum samples of 48 patients admitted
      for digestive endoscopy. The data of the serologic tests were compared with those
      provided by the culture, the histologic observation and the urease test of
      gastric biopsy specimens. The calculation of seroprevalence of anti-H. pylori
      antibodies in serum of 60 asymptomatic subjects was carried out. RESULTS: The
      seroprevalence of infection by H. pylori in an asymptomatic population of between
      18 to 78 years of age was 58.33%. A sensitivity of 94.3% and a specificity of
      88.9% were observed with the Pyloriset EIA-G test. The positive predictive value
      (PPV) was 92.2% and the negative predictive value (NPV) 91.5%. With the
      Chemifarma commercial kit the sensitivity was 78.8% and the specificity 100% with
      a PPV of 100% and NPV of 76.7%. Plate showed a sensitivity of 85.3% and a
      specificity of 87.5% with a PPV of 90% and a NPV of 80.76%. Milenia had a
      sensitivity of 80% and a specificity of 66.7% and a PPV of 77% and a NPV of
      70.7%. CONCLUSIONS: The usefulness of the serologic tests for the diagnosis of
      Helicobacter pylori infection is herein confirmed with the test evaluated showing
      a high sensitivity and specificity as well as high predictive values.

PMID- 9646564
TI  - [Diabetic foot: a path leading to avoidable amputation].

PMID- 9646565
TI  - [Painful costal tumor in an HIV-positive patient].

PMID- 9646566
TI  - [Cutaneous nodules and arm paresthesia].

PMID- 9646567
TI  - [Retrommamary abscess caused by Nocardia asteroides in HIV-positive patient].

PMID- 9646568
TI  - [Mycobacteria retrieval with the MB-Check system].

PMID- 9646569
TI  - [Hematogenous osteomyelitis of the tibia caused by Eikenella corrodens].

PMID- 9646570
TI  - [Nephrogenous diabetes insipidus secondary to the administration of amphotericin
      B and liposomal amphotericin B].

PMID- 9646571
TI  - [Hip septic arthritis as presentation form of acute appendicitis].

PMID- 9646572
TI  - [Wound infection caused by Vibrio parahaemolyticus].

PMID- 9646573
TI  - [Thyroiditis caused by Pneumocystis carinii in a patient with HIV infection].

PMID- 9646574
TI  - [Ocular infection caused by Aeromonas spp.: considerations on its treatment and
      importance of resistance to antimicrobial agents].

PMID- 9646575
TI  - [Antibodies against prolactin in patients with systemic lupus erythematosus and
      hyperprolactinemia].
AB  - We investigated patients with lupus erythematosus to detect the presence of
      hyperprolactinemia and to determine it's origin. From the seric specimens
      obtained in 225 patients with LES, we found 37 (14.5%) with hyperprolactinemia
      and they were trated with polyethylenglicol, in 11 of 37 patients (29.7%) had a
      high significance of prolactin precipitation (PRL). The test in gel filtration
      shown the big-big PRL (Molecular weight > 100 kDa) was the predominant form from
      PRL seric in these patients and no woman had clinic effects of hyperprolactinemia
      as galactorrhea and/or amenorrhea. The big-big PRL essence was due to an
      antibody, with it was found like a immune complex (Ig-PRL). This evidence suggest
      the patients with LES and hyperprolactinemia have a very high incidence of
      macroprolactinemia relationated to antibodies anti-PRL, and in spite of the
      hyperprolactinemia not have clinical effects like amenorrhea and/or galactorrhea,
      and it is other cause to explain the high incidence of hyperprolactinemia in
      patients with LES.

PMID- 9646576
TI  - [Radiologic, densitometric, morphologic and electron microscopic study of
      osteoporosis and osteopenia in the third lumbar vertebra in men and women in the
      city of Mexico].
AB  - OBJECTIVE: To determine bone density in the third lumbar vertebra in a group of
      men and women from the Mexico City correlating the morphometric characteristics
      of vertebral body by specific techniques and to detect groups with alterations
      like osteoporosis or osteopenia. METHODOLOGY: The study was made in third lumbar
      vertebra from 23 patients dead of the Medical Service Forense-Mexico, 8 women
      between 31 to 72 years old and 15 men between 25 yo 62 years old. The studies
      were: Radiological, bone densitometry and by image in which was determined
      density of vertical and horizontal trabeculaes. With x-ray technique in scanning
      electron microscopy was determined in form semiquantitative the presence of Ca,
      P, Mg and Na, and Ca distribution by technique of x-ray energy dispersed.
      RESULTS: In the radiological trail all vertebras of the female group were
      abnormal, the major finding was degenerative feature; 5 Showed trabeculation
      increased 3 fractured; in the males group 7 patients were normal, degenerative
      fracture in 8; of these six had densitometry with DEXA; in the females group only
      one was normal, 3 osteopenia, 5 osteoporosis; in the male group: 5 osteopenia and
      5 osteoporosis. Scanning electron microscopy examination exhibit a homogeneous
      and dense expression pattern, wherever SEM demonstrated the absence or decrease
      of deposit calcium in osteoporosis. A morphometric examination of the trabecular
      thickness demonstrates a difference between the two sexes. The normal median was
      222.1 microns, the osteoporosis range was 126.3 to 156.2 microns in the female
      osteoporosis, in male group was found two normal values with a trabecular density
      mean of 249.7 microns, in the last two cases one with osteopenia and the other
      with osteoporosis, the mean value was 186.4 microns. CONCLUSIONS: In the present
      study, was demonstrated that the degenerative alterations in osteoporosis and
      osteopenia in young people are more frequent to respect other reports. The
      following observations require special emphasis either because they provide clues
      to the mechanism of altered expression of calcium: Genetic, ethnic, consume,
      sedentary and others.

PMID- 9646577
TI  - [Apoptosis and extracellular matrix degradation in chorio-amnion during labor and
      premature membrane rupture].
AB  - BACKGROUND: The molecular mechanisms of chorioamniotics membranes rupture during
      labor are relationated with a group of enzymes named metalloproteinases of
      extracellular matrix (MMP), the production of these enzymes are elevated in
      premature rupture of membranes. The collagenase IV (molecular weight 92 kDa) is
      induced in specific form during both events. We unknown the regulatory mechanisms
      to these enzymes in the chorioamnios. OBJECTIVE: To determine the presence of
      apoptosis and expression of (MMP-) in human chorioamnios during the labor and
      premature of the fetal membranes. MATERIAL AND METHODS: The gel lysis using
      zimography was determined in membranes of 1) Labor, 2) Cesarean section, 3) PRM.
      The analysis of DNA fragmentation in situ and DNA of the membranes was studied.
      Using immunohistochemistry techniques was identified MMP-9. RESULTS: It was
      observed increase of gel lysis in stracts with PRM and labor in comparation with
      cesarean section. In all the specimens were found apoptotics cells, however, they
      were scareces, abundance or very abundance in cesarean section specimens, labor
      or PRM respectively. The fragmentation in situ was confirmed in specimens of DNA.
      The immunohistochemistry showed positively to MMP-9 in labor and PRM specimens,
      and not in cesarean section specimens. The MMP-9 immunorreactivity was extensive
      in PRM and only was found apoptosis. CONCLUSIONS: The results demonstrate that
      apoptosis and expression-activity of MMP-9 can be associated to membranes rupture
      during labor and lysis, the same explanation may be true for the increased
      expression of MMP-9 in PRM both phenomena seems to have a sequence.

PMID- 9646578
TI  - [A new parameter for the evaluation of premature luteinization: the pre-ovulatory
      molecular relation between serum concentrations of progesterone and estradiol].
AB  - The objective was to evaluate the molecular ratio between the serum levels of
      progesterone (P) and estradiol (E2) and to determine it's effect on the in vitro
      fertilization performance. Sixty two couples were studied, the molecular P:E2
      ratio was established the day of human chorionic gonadotropin (hCG) injection.
      The mean serum P concentration the day of hCG administration 1.45 +/- 0.50 ng/mL,
      while the mean P:E2 ratio was 0.63 +/- 0. Pregnancies were observed since
      molecular ration of 0.22, no pregnancies were obtained if the molecular ratio was
      > 1.02. No significant difference was detected in the fertilization and pregnancy
      rates in the patients who have or not premature luteinization. The implantation
      rate was low in patients with premature luteinization, however, there was not
      significant difference with patients without premature luteinization. In
      conclusion, the P:E2 ratio surrounding 1.0 is desirable to obtain adequate
      results in in vitro fertilization programs. In this work as others, the premature
      luteinization do not have effect in the reproductive results.

PMID- 9646579
TI  - [Ovum donation: a 3-year experience at the Gynecologic and Obstetric Center of
      Monterrey, Mexico].
AB  - OBJECTIVE: Evaluating the rate of pregnancies, neonates, implantation rate and
      kinds of donor in our program Assisted Reproduction with oocyte donation.
      INTRODUCTION: The oocyte donation is the most important support in assisted
      reproduction because in patients with ovarian failure, offering the same
      opportunity to female without ovarian alterations to increase the rate of
      pregnancies. MATERIAL AND METHOD: 98 donor's procedures were included in host
      patients; 87 were FIV-TE and 11 GIFT between march to june 1997. The patients
      were divided in age group: 1) < 30 years, 2) 30 to 34 years, 3) 35 to 39 years,
      4) > or = 40 years. The donors were divided in known (26) and unknown (72). The
      results were analysed. RESULTS: 48 pregnancies (55.17%) of the 87 FIV-TE-D group
      were obtained with 31 neonates The implantation rate was 17.5% to FIV-TE group
      and 13.8 to GIFT group, 44 (61.11%) pregnancies were from unknown donors group
      and 9 (34.61%) from known donors group. CONCLUSIONS: Our results are similar to
      others international reports, we have observed a little and significative
      difference between pregnancy with oocytes from known donors and unknown donors;
      this is the principal motive to be selective in the suitable known donor.

PMID- 9646580
TI  - A dose of prevention.

PMID- 9646581
TI  - Two automated perimeters.

PMID- 9646582
TI  - UCB's 75th anniversary: Cal's proud legacy of the twentieth century provides new
      promise at the millenium.

PMID- 9646583
TI  - Essentials in fitting ocular prostheses for complex congenital and acquired
      anomalies.
AB  - BACKGROUND: Providing ocular prosthetic services is an important aspect of total
      patient care. A patient who has lost an eye to injury, inflammation, or tumor
      experiences emotional and psychological trauma similar to that experienced by an
      amputatee. Congenital absence also creates a special set of circumstances. A
      prosthesis that is lifelike in appearance is a comfort to the patient, and the
      physical wearing comfort becomes a primary prerequisite for the patient. CASE
      REPORTS: A variety of congenital and acquired anomalies are used to illustrate
      the clinical application of modern-day materials used to fabricate and fit ocular
      prostheses. A comprehensive evaluative protocol is also presented. CONCLUSION:
      New materials and better fitting techniques allow more patients to wear
      prostheses greater comfort and cosmetic approval. The primary care optometrist
      should be familiar with the options available to the patient and the standard of
      care in evaluation of patients who wear a prosthesis.

PMID- 9646584
TI  - History of contact lenses at the University of California, Berkeley, School of
      Optometry.

PMID- 9646585
TI  - Berkeley optometry: clinical training into the 21st century.

PMID- 9646586
TI  - Sports medicine and the eye care professional.
AB  - BACKGROUND: There are more than 40,000 eye injuries every year in the United
      States--many of which are sports-related. Sports injuries are a common cause of
      severe vision loss. Today, contact sports, racket sports, and other high-risk
      athletic activities are more popular on an organized and informal level. Those
      engaging in these activities should wear the proper eye and facial protection, so
      as to minimize the risk of severe injury and potential vision loss. CASE REPORTS:
      Case studies are used to illustrate examples of sports-related clinical
      experiences encountered in a primary care practice. A description of protective
      devices, a discussion of product liability, the standard of care, and the
      doctor's responsibility to the patient complement the case scenarios. Emphasis is
      placed on prevention and particular attention should be paid to the patient at
      high risk and to the one-eyed patient. CONCLUSION: Sports-related eye injuries
      have a high risk for ocular morbidity and subsequent severe vision loss. Many
      sports related injuries are preventable and the primary care practitioner can
      provide important information and education regarding protection and avoidance
      for those participating in high-risk activities. The provider should promote
      compliance and be adequately informed as to product liability, standards,
      manufacturers of the devices, and indications for the use of specific devices.

PMID- 9646587
TI  - "Health care law and politics: failure of patient care", a view since 1995.
AB  - To eliminate the budget deficit in seven years, the Congress of the United States
      is engaged in revising thirty years of American health care policy. Medicaid
      health benefits for 30 million low-income disabled (of which 46% are children)
      would be turned into a state-by-state block grant, with virtually total
      individual state discretion to determine eligibility and covered services.
      Medicare, providing health care for 37 million elderly, is about to change the
      fee for service system into organized cluster systems of managed care.

PMID- 9646588
TI  - An unusual case of wrongful pregnancy: liability of doctor resulting from
      misrepresentation.
AB  - A married woman and her husband recovered damages from a gynaecologist after the
      woman gave birth to a third and normal child. The couple's second child had been
      delivered by way of Caesarean section. Six days after its delivery the doctor
      made the statement (erroneously) that he had performed a tubular ligation on the
      woman, following a discussion on the advisability of sterilisation. In fact no
      such procedure had been performed. The woman became pregnant again. The doctor
      was held liable on the basis of a negligent misrepresentation.

PMID- 9646589
TI  - Evidential damage as a result of improper medical records.
AB  - The article provides a summary of the development and definition of the cause of
      action described by the Israeli courts as "evidential damage". This cause of
      action stems from the duty placed on health care providers to keep proper,
      complete and accurate records of diagnoses and medical treatments administered to
      patients. This duty was first developed by the courts and then recently codified
      in the Patients' Rights Law passed in 1996. Initially the courts in Israel
      recognised that the failure to keep proper medical records could only shift the
      burden of evidence from the plaintiff to the defendant, but the requirement to
      show negligence still remained. Eventually the courts recognised that the failure
      to keep proper medical records, in itself could bar a plaintiff's ability to
      prove his claim, and therefore they determined this to be an independent cause of
      action, which can be compensated to the extent of the damage caused by the
      medical incident which was not properly documented.

PMID- 9646590
TI  - Intended blinders in research.
AB  - It could be argued that science is the only generally recognised cognitive
      authority in the world today. Science is not constrained by frontiers between
      countries. The art of science is influenced by more factors, how entrenched ideas
      govern scientific beliefs, also by talent, trends, politics, lobbying, peer
      review, priority, conflict of interest etc. Therefore what might have occurred in
      concealment, is of common scientific interest. An actual example from Denmark is
      presented showing how research into patients rights and consumer protection has
      been employed as a technical stumbling-block by health authorities. The
      authorities problem was certainly a political, not intrinsically a practical
      medical or scientific one.

PMID- 9646591
TI  - Deaths on the table: proposal for an international convention on the
      investigation and prevention of anaesthetic mortality.
AB  - National and international variations in clinical practice, study methodologies,
      and data collection make the estimation of patient deaths attributable in some
      measure to anaesthesia a difficult task. Such rates have undoubtedly
      significantly declined, a tribute, in large part, to the work of groups such as
      the International Committee for the Prevention of Anaesthetic Mortality and
      Morbidity, the Anesthesia Patient Safety Foundation and the Australian Patient
      Safety Foundation. There is, however, internationally, still a significant risk
      of mortality associated with anaesthesia which is distinct from that related to
      any relevant surgery or intercurrent disease. As a matter of pure logic, patients
      worldwide should be entitled to expect a basic minimum of knowledge and skills
      from an anaesthetist, as well as his or her use of standard monitoring equipment.
      In an age where the global provision of health services and equipment may be
      increasingly dominated, under trade-promoting international agreements, by a few
      trans-national corporations, and where technology facilitates dissemination of
      medical data, a unified, worldwide approach to the investigation and prevention
      of anaesthetic mortality appears both rational and urgent. The benefits of an
      investigatory system, focused on subsequent safety rather than present liability
      and standardized through International Conventions, are well established in the
      air transport industry. We urge the involvement of persons with political and
      legal expertise in the development of an International Convention for the
      Investigation and Prevention of Anaesthetic Mortality.

PMID- 9646592
TI  - Forensic urology: a practical vision.
AB  - Urologists enjoying the protection of the law owe a duty to participate in the
      legal system as expert witnesses. Forensic education has been neglected by
      clinical educators. Qualification of experts includes forensic as well as
      clinical competence. The forensic urologist must know legal concepts and
      language; the powers, duties, and role of courtroom experts. The expert witness'
      role is to factually enlighten the judges, not to persuade them. Practical
      measures to remedy the current state of affairs are described from over a decade
      of experience. These practical measures should be supplemented by the formal
      development of a subspecialty of Forensic Urology sponsored by our colleges and
      professional societies.

PMID- 9646593
TI  - Maternal weight and fetal injury at birth: data deriving from medico-legal
      research.
AB  - The relationships among maternal weight, gestational weight gain, fetal birth
      weight and birth injuries have been investigated in connection with 62 cases of
      shoulder dystocia that involved permanent impairment of the newborn or neonatal
      demise. A high prevalence of > 13.5 kgs. gestational weight increase between the
      first and last office visits (62%) obesity expressed as > or = 87 kg. body weight
      at term (64.1%) and > or = 4000 gm. birth weight (80%) was found in this group of
      patients. The results indicate that the relationship between excessive maternal
      and fetal body weights and shoulder dystocia related fetal or neonatal impairment
      is closer than previous studies have suggested. These results underline the
      importance of appropriate and intensive nutritional counselling of the mother
      throughout pregnancy, noting that arrest of the shoulders is only one of those
      obstetric complications that are closely related to maternal obesity. The
      findings underline the usefulness of medico-legal reviews in clinical research.

PMID- 9646594
TI  - Forensic psychiatric evaluation: clinical, ethical and procedural issues in South
      Africa.
AB  - Evaluations done by the Forensic Psychiatrist take place in relation to various
      situations and in circumstances of a statutory nature and include clinical
      assessments for treatment, management and rehabilitation. Numerous issues in the
      field of legal process and ethical dilemmas are discussed. Conflicts with the
      traditional role occur and continued awareness of this is relevant for the
      maintenance of standards in the whole of psychiatry. Advocacy for better
      conditions for mentally ill offenders and consultation with state legislatures
      regarding changes in the criminal justice system and other relevant procedures
      are recommended. This is most significant especially for the indigent defendant
      and to allay public issues of the client referred, as well as those who
      ultimately become patients.

PMID- 9646595
TI  - Transinstitutionalization and an overburdened judicial system.
AB  - The author discusses punishment in the United States in the context of increasing
      transinstitutionalization. He believes that the administration of justice has
      become more complex, in part because of plea bargaining and pleading reforms,
      often does not allow the application of judicial fairness, and has lost its
      deterrent effect on criminal offenders. He proposes the necessity for a
      reorganization of the roles of the various social institutions.

PMID- 9646596
TI  - Late termination of pregnancy in cases of severe abnormalities in the fetus.
AB  - Developments in medical technology have increased the possibility of diagnosing
      severe structural abnormalities in the fetus. In such circumstances, the woman
      may request termination of her pregnancy. This raises serious ethical and legal
      questions, in particular if the abnormalities are discovered after 24 weeks of
      gestation, when the fetus is considered viable. This article discusses the legal
      aspects of this problem, with particular reference to the Netherlands. If one
      accepts that, in exceptional circumstances, third trimester abortion may be
      justified on medical grounds, the law should make provision for it. However, the
      general protection provided by the law to fetal life-especially in the third
      trimester--should remain firmly in place.

PMID- 9646597
TI  - Artificial reproduction and the family of the future.
AB  - The techniques of artificial reproduction have until fairly recently been geared
      to overcoming male sterility by means of AID and IPSI and female sterility by way
      of GIFT, VISPER and DIPI. The above techniques have concentrated on achieving
      conception either within or without the uterus. Gestation has always been
      completed in utero and the therapy was reserved for married couples. The above
      circumstances only required limited legal regulation and its effect on the family
      unit was minimal because the child was mostly conceived from the gametes of its
      parents New technologies which are looming on the horizon, however, threaten to
      change the concept of parent and family radically. I refer to the imminent
      perfection of the artificial uterus and the cloning of human cells. If these
      technologies are sanctioned, a child would be conceived from the cells of one
      parent only and will not be gestated within the mother's womb. How will society
      and the law react to these technologies? Will they regulate them or proscribe
      them? I will argue in favour of the former rather than the latter.

PMID- 9646598
TI  - Case consultation: ablatio penis.
AB  - In male infants, traumatic ablation of the penis, with or without loss of the
      testicles may occur as a sequel to mutilatory violence, accidental injury, or
      circumcision error. Post-traumatically, one program of case management is
      surgical sex reassignment to live as a girl, with female hormonal therapy at the
      age of puberty. The other program is genital reconstructive surgery to live as a
      boy, with male hormonal therapy at puberty if the testicles are missing. In both
      programs, the long term outcome is less than perfect and is contingent on
      intervening variables that include societal ideology; surgical technology;
      juvenile and adolescent timing and frequency of hospital admissions construed by
      the child as nosocomial abuse; development of body image; health and sex
      education; fertility versus sterility; coitus and orgasm; possible lesbian
      orientation if living as a girl; and long-term cost accounting, including the
      psychic cost of being a pawn in possible malpractice litigation on whose
      disability a very large fortune in compensation may devolve. There is, as yet, no
      unanimously endorsed set of guidelines for the treatment of genital trauma and
      mutilation in infancy, and no provision for a statistical depository for outcome
      data.

PMID- 9646599
TI  - Informed consent and extended operations.
AB  - This article concerns the extended operations or procedures where during an
      operation, previously agreed between surgeon and patient and while the patient is
      anaesthetised, the surgeon realizes that further or totally different measures
      should be, or may be taken. In this contribution the author defends a strict
      point of view concerning "extended operations". If during the operation, the
      surgeon discovers that other measures should be taken, he may proceed if there is
      an emergency. A more pragmatic view would violate the right to self
      determination.

PMID- 9646600
TI  - Outcomes of regular versus extended outpatient alcohol/drug treatment. Part II.
      Medical, psychiatric, legal and social problems.
AB  - Alcohol and drug patients were placed into two groups in order to study
      differences in outcome based on treatment duration. One group received regular
      outpatient treatment of 90 days (n = 103), and the other received extended
      outpatient treatment of 180 days (n = 127). Most patients received 30 days of
      inpatient stabilization treatment before placement into outpatient. METHODS:
      Patients were randomized into the two groups, and interviewed at discharge, and
      three and six months post-discharge. Data were analyzed using chi-square, t-test,
      and multivariate logistic regression techniques. RESULTS: There were no major
      differences between the two groups in the numbers reporting subsequent drug use,
      or medical, psychiatric, legal, and social problems. However, in terms of
      ancillary effects, the extended treatment group had slightly more desirable
      outcomes with respect to doctor's visits, arrests, or being a homemaker at three
      and six months post-discharge. Post-discharge medical problems, in terms of
      doctor's office visits, were predictable by longer treatment duration, pre
      treatment cocaine use as primary drug, and pre-treatment heroin use as secondary
      drug. Patients were most likely to live with parents, roommates, or alone.
      Whereas abstinence was related to stability in living arrangements, aftercare
      attendance and heroin use were related to unstable living situations.

PMID- 9646601
TI  - [From obstacles, to become a good pharmacist].

PMID- 9646602
TI  - [Treatment of post-traumatic headaches. Recommendations of the German Migraine
      and Headache Society].

PMID- 9646603
TI  - [Diagnostic procedures in venous thrombosis of the legs].

PMID- 9646604
TI  - [Venous thromboembolism. Anticoagulation and thrombolysis].

PMID- 9646605
TI  - [Vomiting after the first trimester of pregnancy: an alarming symptom].
AB  - Nausea and vomiting are common problems of pregnancy. Three pregnant women, 27,
      25 and 28 years of age, presented with vomiting in the third trimester. The
      causes appeared to be maternal small bowel volvulus, which was derotated after
      primary caesarean section, an ileocecal abscess, which was the first
      manifestation of Crohn's disease, and acute pyelonephritis, treated with
      cefuroxim. The second and third babies were born spontaneously; no maternal or
      foetal mortality occurred. Persistent vomiting after the first trimester of
      pregnancy should be considered an alarm symptom which always requires further
      investigation.

PMID- 9646606
TI  - [Notes on the visitation of medical schools in 1997].
AB  - The members of the Visitation Committee who audited the medical education process
      in the Netherlands carefully formed their opinions based on a vast amount of
      information. Their judgement can be considered fair and well-balanced. Several
      critical remarks were made, especially on the coaching of students during their
      internships. The scientific education was also found wanting. Some faculties were
      given bad marks, and scores of recommendations were made. Surprisingly, however,
      the committee was of the opinion that students graduating from all faculties were
      equally and sufficiently competent to enter the medical workforce. It is
      recommended that next time this audit process be carried out on a much smaller
      scale.

PMID- 9646607
TI  - [Immunology in medical practice. IV. Mechanisms in the development of primary
      nephropathies].
AB  - Humoral immunological reactions play a central part in the development of
      nephropathies. Immune complexes may form in the circulation and precipitate in
      the kidney, or form in the kidney by binding of antibodies from the circulation
      to antigens in the glomerular basement membrane. The localizations of immune
      complex deposition in the various compartments of the glomeruli determine the
      development of different forms of glomerulonephritis. Cellular immunological
      reactions play a part in the development of tubulo-interstitial nephritis and
      possibly also of minimal change nephropathy' and focal segmental
      glomerulosclerosis. The role of cellular immunological reactions in the
      development of most other nephropathies is less clear. Persistence of
      nephropathies leads to glomerulosclerosis and renal interstitial fibrosis.
      Ultimately, these cause loss of kidney function and necessitate haemodialysis.

PMID- 9646608
TI  - [Immunosuppressive therapy for idiopathic membranous glomerulopathy].
AB  - Idiopathic membranous nephropathy is the most frequent cause of nephrotic
      syndrome in adults. The natural course of idiopathic membranous nephropathy is
      characterized by a high incidence of spontaneous remissions. Some 50% of the
      patients reach end-stage renal disease. Treatment with corticosteroids alone is
      not efficacious; treatment with a combination of immunosuppressive drugs improves
      renal survival. However, because of the high incidence of spontaneous remissions
      and the risk of treatment-related toxicity, immunosuppressive treatment should be
      reserved for patients with proven renal insufficiency. Cyclophosphamide appears
      to be more efficacious and better tolerated than chlorambucil. Identification of
      high-risk patients at an early stage of the renal disease may contribute to a
      more efficient use of immunosuppressive treatment.

PMID- 9646609
TI  - [Clinical thinking and decision making in practice. A patient with decreased
      vision and a skin disorder].
AB  - In a 48-year-old man who suffered from progressive loss of vision in his left eye
      and metamorphopsia, pseudoxanthoma elasticum was diagnosed. Angioid streaks were
      observed in both eyes and the skin showed small yellow papules in a linear
      pattern. The right retina was twice treated by laser coagulation which resulted
      in temporary regression of neovascularization. Pseudoxanthoma elasticum is a
      genetic disorder with variable penetrance. There is no treatment. Patients should
      be told to refrain from contact sports and to avoid using aspirin.

PMID- 9646610
TI  - [Mammographic surveillance of breast cancer patient relatives; implementation of
      guidelines formulated by the Netherlands College of General Practitioners].
AB  - OBJECTIVE: To determine the implementation of the guidelines for mammographic
      screening of breast cancer relatives formulated by the Dutch College of General
      Practitioners (NHG), in daily practice. DESIGN: Prospective, descriptive.
      SETTING: Kennemer Gasthuis, location EG, Haarlem, the Netherlands. METHODS: For
      all asymptomatic women referred for mammography to our department of radiology by
      their general practitioners between January 1, 1992 and August 1, 1995 because of
      a family history of breast cancer, who had normal or benign radiological findings
      and fulfilled the NHG criteria (aged 35 years or older with a first degree family
      history of breast cancer), we advised a repeat mammogram within 1-2 years. After
      2 years we checked in the hospital information system whether or not a patient
      had undergone repeat mammography in the Kennemer Gasthuis; in case of non
      reattendance at this hospital general practitioners were asked by questionnaire,
      and if necessary by telephone, if follow-up mammography had been performed
      elsewhere. RESULTS: Out of the 510 referred women, 405 (79.4%) met the NHG
      criteria. In 370 the radiological findings were 'normal' or 'benign' and the
      follow-up data were complete. Of these 370 women 201 (54.3%) underwent a repeat
      mammogram within two years. This examination was performed more often if breast
      cancer of a first degree relative had been diagnosed premenopausally (126/208 =
      60.6%) rather than postmenopausally (75/162 = 46.3%; 95% confidence interval for
      the difference: 3.6-25.0). CONCLUSION: General practitioners in 50% of the cases
      complied with the recommendations for regular mammographic screening of breast
      cancer relatives. Their compliance may be increased by introduction of simple
      procedures into the computerized system for identification of risk factors and a
      systematic planning of screening examinations.

PMID- 9646611
TI  - [Recommended dietary allowance of folic acid is insufficient for optimal
      homocysteine levels].
AB  - OBJECTIVE: To determine the effect of short term supplementation of vitamin B6
      (pyridoxine) followed by folic acid in apparently healthy volunteers on the
      fasting plasma homocysteine concentrations (hyperhomocysteinaemia is an
      independent risk factor for premature atherosclerosis). DESIGN: Prospective,
      descriptive. SETTING: Academic Hospital Groningen, the Netherlands. METHODS:
      Apparently healthy Dutch volunteers, aged 20-75 years, were supplemented with
      vitamin B6 1 mg/kg/day during 7 days followed by folic acid 5 mg/day during
      another 7 days. On days 0, 7 and 14 the fasting plasma homocysteine
      concentrations were measured. A change of an individual's plasma homocysteine
      level was considered statistically significant if the change in percentage
      exceeded 2.8 times the sum of the analytical and the intraindividual biological
      variation. RESULTS: There were 103 participants, 45 males and 58 females, with
      average ages of 43 and 44 years, respectively (on day 7, data were available on
      101 participants). Baseline folic acid concentrations of all participants were
      above the lower limit of the reference range. Eight and two of them had vitamin
      B6 and vitamin B12 concentrations below the reference range, respectively. Plasma
      homocysteine was inversely related to plasma levels of folic acid and vitamin B12
      at that moment. During vitamin B6 supplementation the mean plasma homocysteine
      level did not change; one participant exhibited a significant plasma homocysteine
      decrease. During folic acid supplementation the mean plasma homocysteine
      decreased from 11.7 mumol/l (SD: 5.6) to 9.1 (SD: 3.4); 40 participants (40%)
      exhibited significant plasma homocysteine decreases. At the end of the study
      plasma homocysteine was still related to plasma vitamin B12. CONCLUSION: The
      folic acid status of the participants at baseline was not associated with the
      lowest plasma homocysteine levels. Since atherosclerosis risk may increase
      continuously with increasing plasma homocysteine, it may be wise to keep plasma
      homocysteine levels as low as possible. To reach this goal, the recommended
      dietary allowance of folic acid may have to be increased.

PMID- 9646612
TI  - [Primary peritonitis due to Streptococcus pneumoniae in childhood].
AB  - Three patients, two boys of 5 months and 6 years and one girl aged 4 years,
      presented with acute abdominal pain, vomiting and fever, suggesting peritonitis.
      Imaging examinations (abdominal survey roentgenogram and (or) echography),
      exploratory laparotomy (in two patients) and blood cultures with growth of
      Streptococcus pneumoniae led to the diagnosis of primary peritonitis. Intravenous
      antibiotics led to recovery, in one patient complicated by paralytic ileus, which
      was treated surgically. Primary peritonitis is a rare condition which should be
      considered in the differential diagnosis of children with an acute abdominal
      syndrome. Conditions requiring surgery should be excluded by imaging examinations
      or laparotomy. When the diagnosis is confirmed by paracentesis or laparotomy,
      antibiotic treatment has to be started.

PMID- 9646613
TI  - [Impressions on the thighs; semicircular lipoatrophy].
AB  - An otherwise healthy woman aged 28 had symmetrical band-shaped dents on both
      thighs. She worked as a secretary; several female colleagues showed identical
      lesions. An investigation showed that the arrangement of the office equipment
      combined with sharp-edged desk tops caused these abnormalities. The diagnosis
      made read 'semicircular lipoatrophy caused by repetitive leaning against a desk'.
      This is probably a common problem, although it rarely leads to consultation of a
      dermatologist.

PMID- 9646614
TI  - [The significance of publication in Dutch medical journals using an external peer
      review system].
AB  - Impact factors of the journals in which scientific work is published play an
      important part in the assessment of scientific research. Impact factors are
      determined by the number of citations in the international literature of articles
      published in journals which are indexed by Current Contents (Science Citation
      Index). Publications in Dutch scientific journals-not admitted to Current
      Contents--such as Nederlands Tijdschrift voor Geneeskunde ('Dutch Medical
      Journal')--score lower in the assessment of scientific research. At a conference
      organized by Nederlands Tijdschrift voor Geneeskunde it was emphasized that there
      should be more appreciation for the transfer of medical knowledge and experience
      in the Dutch language. It is estimated that not more than about 10% of the Dutch
      physicians read foreign medical journals. Publications in the Dutch language have
      an important role in the teaching process and affect the quality of health care.
      Scientific medical publications should not be judged only by the impact score
      based on the Science Citation Index. There should be a second scoring system for
      publications in Dutch medical journals using an external peer review system which
      are not admitted to Current Contents.

PMID- 9646615
TI  - [Visitation of medical schools in 1997].
AB  - The visitation committee medicine and health studies in 1997 visited all eight
      Dutch medical schools. A quality judgement was formed based on the results of a
      self-analysis of these schools and extensive research on the spot. The conclusion
      was that all schools inspected turn out physicians who can be trusted to do their
      work well. However, the committee judges the curricula of some of the schools to
      be very traditional: too much oriented towards the basic sciences with hardly any
      room for contributions of the students themselves.

PMID- 9646616
TI  - [Medical decisions made by teams: carefulness and responsibility].
AB  - To a growing extent, medical decision making takes place in the context of a
      team. Where multidisciplinary cooperation is necessary and the decisions to be
      taken are complex and consequential (in particular at the beginning and the end
      of life) joint decision making is considered an essential requirement of careful
      medical practice. From a legal point of view, this raises the question who is
      accountable for such decisions. Basically, accountability (and the liability that
      may result from it) will stay with the individual participants, and in particular
      with the first responsible, attending physician. In this respect, decision making
      in such situations is not basically different from other, more informal
      consultation structures (such as regular case reviews at department level) which
      are current practice in many health care institutions. Finally, if joint decision
      making is required, it should be clear in advance how decisions are to be arrived
      at in the team.

PMID- 9646617
TI  - [Inventory and follow-up of patients with surgery for (uterine) vaginal prolapse,
      combined with or without, (masked) stress incontinence].

PMID- 9646618
TI  - [Penicillin: just in time].

PMID- 9646619
TI  - Vastatin trials: lessons from hypertension history.

PMID- 9646620
TI  - Human volunteer studies in consumer product research.

PMID- 9646621
TI  - Efficacy and safety of a new cholesterol synthesis inhibitor, atorvastatin, in
      comparison with simvastatin and pravastatin, in subjects with
      hypercholesterolemia.
AB  - BACKGROUND: High levels of total and LDL-cholesterol are associated with an
      increased risk of atherosclerotic vascular disease. Lowering of serum cholesterol
      levels by pharmacologic intervention with inhibitors of cholesterol synthesis,
      the so-called statins, reduces the incidence of cardiovascular events in subjects
      with and without atherosclerotic manifestations. In a 16-week, multicenter,
      randomized, open-label cross-over study we compared the efficacy and safety of
      the new compound atorvastatin for reducing LDL-cholesterol with simvastatin or
      pravastatin. METHODS: Following a 4-week placebo-controlled baseline period
      patients with LDL-cholesterol between 4.1 and 6.2 mmol/l and serum triglycerides
      below 3.4 mmol/l were randomly assigned to treatment either with 5 or 20 mg
      atorvastatin, or with 10 mg simvastatin or 20 mg pravastatin once daily for 4
      weeks. After a placebo-washout period of 4-6 weeks, patients switched to the
      alternate treatment. At the end of weeks 3 and 4 of each study phase the serum
      concentrations of lipid parameters and apolipoproteins as well as safety
      parameters were determined. RESULTS: A total of 78 subjects entered the study.
      Treatment with 5 mg atorvastatin reduced total and LDL-cholesterol by 21 and 27%,
      respectively, which was similar to 10 mg simvastatin (total cholesterol -20%, LDL
      cholesterol -28%) and 20 mg pravastatin (-18 and -24%, respectively). The effects
      of this low dose of atorvastatin on triglyceride levels (-16%) was not different
      from that of simvastatin and pravastatin (-8 and -11%, respectively). Treatment
      with 20 mg atorvastatin caused significantly larger reductions in total
      cholesterol (-33%) and LDL-cholesterol (-44%), serum triglycerides (-23%), and
      apo B (-40%) compared to simvastatin and pravastatin. Atorvastatin was well
      tolerated, and no serious or medically important adverse events were observed.
      CONCLUSIONS: We conclude that atorvastatin is a safe and very efficacious
      cholesterol-lowering agent, which also possesses significant triglyceride
      lowering properties.

PMID- 9646622
TI  - Ethical review of human experimentation in the consumer products industry.
AB  - BACKGROUND: Ethical review of human experimentation in the consumer products
      industry is important and provides instructive parallels and contrasts with
      clinical medical research. The procedures used in Unilever NV/plc are described.
      METHODS: A central body sets standards for and monitors compliance with ethical
      review of human studies throughout Unilever. Guidance has been produced on many
      topics including issues applying generally to human experimentation and more
      specifically to the consumer products sector. RESULTS: Deficiencies and
      inconsistencies in the procedures for ethical review and the care of subjects
      during the conduct of studies have been identified and corrected. Appropriate
      uniform standards have been achieved across all Unilever operations. CONCLUSION:
      All human experimentation in the industry needs adequate ethical review. Although
      the methods used by individual companies may differ, procedures must ensure
      uniform high standards across a global industry.

PMID- 9646623
TI  - Ischaemic colitis and lung infiltrates caused by extramedullary haematopoiesis in
      a patient with an acute erythroid leukaemia following polycythaemia vera.
AB  - A patient with 'spent' polycythaemia vera showed extensive extramedullary
      haematopoiesis (EMH) in non-haematopoietic tissue clinically resulting in an
      ischaemic colitis and respiratory symptoms due to lung infiltrates. On laboratory
      investigation, the EMH also included immature erythroblasts due to acute
      erythroid leukaemia. It is hypothesised that the abnormal homing of erythroid
      progenitors might be related to the abnormal expression of antigens, such as
      CD36.

PMID- 9646624
TI  - Onset of coeliac disease after a spontaneous miscarriage during a holiday in
      Australia: coincidence or causal relationship?
AB  - Diarrhoea contracted whilst travelling in a (sub)tropical country often has an
      infectious cause. However, dietary changes can also be of importance. We describe
      the case of a 28-year-old woman, who developed severe coeliac disease during a
      trip in the Australian outback. The nutritional history revealed that the
      patient's diet contained more wheat products during her trip than she was used to
      in Holland. Moreover, the onset of symptoms coincided with a spontaneous
      miscarriage of an 8-week-old embryo. This correlation has been described in
      several case reports in the literature. However, the pathophysiologic mechanism
      behind this correlation is unknown. Some speculative mechanisms are proposed
      here. Further investigations into this relationship could increase our
      understanding of the immunopathogenesis of coeliac disease.

PMID- 9646625
TI  - Pneumomediastinum: an unusual complication of bronchial asthma in a young man.
AB  - We report a patient with bronchial asthma who presented with pneumomediastinum,
      pneumopericardium, pneumoretroperitoneum, pneumorrhachis and extensive
      subcutaneous emphysema, after a period of coughing. Pathogenesis, diagnostic
      procedures and treatment of pneumomediastinum and its complications are
      discussed.

PMID- 9646626
TI  - [Abuse of analgesics, headache, family practitioner and neurologist].

PMID- 9646627
TI  - [Response to treatment of chronic daily headache with analgesic abuse].
AB  - The overuse of analgesics in patients with chronic daily headache (CDH)
      perpetuates and worsens the headache. The aim of this study was to evaluate the
      clinical response to withdrawal of analgesics and to preventive treatment in a
      group of patients with CDH. Eighty-four patients who were taking daily
      symptomatic medications, and suffering from CDH were studied. Treatment consisted
      of withdrawal of daily symptomatic medications and prophylactic therapy.
      Improvement was considered when intensity and frequency of the headache were
      reduced more than 50%. After a 2-15 months follow-up, 57 of the 76 patients that
      continued in the study had improved. From these, 98% had reduced the consumption
      of analgesics below the figures considered as abuse and a 94% took the
      prophylactic medications correctly. After giving up the preventive treatment, 26%
      of the patient presented CDH and the 60% overuse again of analgesics. These
      results show that withdrawal of analgesics is necessary for improvement in
      patients with CDH, but the possibility of relapses is elevated. We think that
      there are other factors implicated in the development of CDH. We therefore
      believe that in order to avoid the relapses this group of patients need follow-up
      and preventive treatments during long periods of time.

PMID- 9646628
TI  - [Genetics of mental retardation].
AB  - Mentally retarded patients can be grouped in two categories: severe forms seen in
      4 of every thousand live births and mild forms that occur approximately five
      times more often. Approximately half of severe cases of mental retardation are
      genetically determined, and half of these fall under the category of X-linked
      mental retardation (XLMR) disease. The XLMR group is currently comprised of 105
      highly varied types of retardation that can be associated with a fragile X
      chromosome, biochemical defect, neurologic alterations, bony dysplasia and a
      range of malformations. Along with such syndromes (which are specific), some 40
      familial XLMR entities (nonspecific) can be identified in which mental
      retardation is the only sign. Cytogenetic testing to identify dysmorphic
      syndromes caused by chromosomal disease and molecular biology studies are
      indispensable for identifying the genes responsible for XLMR syndromes. Healthy
      carriers can also be found. It thus becomes possible to provide appropriate
      genetic counseling for families and to achieve a prenatal diagnosis in some
      cases.

PMID- 9646629
TI  - [Current surgical treatment of Chiari type I malformation and Chiari I
      syringomyelia complex].
AB  - Chiari type I malformation and so-called Chiari-I/syringomyelia complex continue
      to inspire controversy. Disagreement on these malformations concern both
      etiopathogenesis and treatment. Our still poor understanding of the natural
      course of the disease, the lack of consensus regarding therapeutic indications
      and even disagreement on appropriate surgery all contribute to cause
      disagreement. Significant progress has been made in our understanding of
      contributing etiopathogenetic factors in recent years. The most widely accepted
      hypothesis is that anomalous embryonic development characterized by paraxial
      mesodermal insufficiency would put volumetric constraints on postnatal
      development of the posterior fossa. We review historical and current
      controversies regarding Chiari type I malformation and classic theories on
      causative and contributing factors. We also discuss the latest surgical
      treatments that have been suggested, as well as associated anomalies--mainly
      syringomyelia, hydrocephalus and malformed cranial-cervical articulation.
      Finally, we propose a protocol useful for the diagnosis and treatment of Chiari
      type I malformation associated with dilation of the ventricular system.

PMID- 9646630
TI  - [Cranial magnetic resonance of a 25-year-old woman with Norman's disease].

PMID- 9646631
TI  - [Familial internal carotid dissection].
AB  - Cervicocerebral arterial dissections is responsible for 20% of first strokes in
      young adults. Several diseases of the connective tissue and wall vessels
      anomalies are considered predisposing of arterial dissection. Familiar cases have
      been reported in 5%, according to hereditary primary arteriopathy, such as
      fibromuscular dysplasia. However, the nature of this arteriopathy has been rarely
      proved. We present two sisters with spontaneous dissection of the internal
      carotid artery with details suggestive of an atypical way of fibromuscular
      dysplasia in one of them.

PMID- 9646632
TI  - [Focal dystonia and tremor secondary to brain stem tuberculoma].
AB  - Brainstem tuberculoma is exceptionally observed. We report a 44 year-old
      immunocompetent man with proven diagnosis of miliary tuberculosis (TBC) who
      developed a complex neurological syndrome characterized by right ophtalmoplegia,
      left-sided hemiparesis and hemihypoesthesia and a gross ipsilateral postural and
      action tremor with hand dystonia. A ponto-mesencephalic mass was detected by CT
      and MRI studies of the brain. Clinical, bacteriological and neuroimaging studies
      allowed to suspect a ponto-mesencephalic tuberculoma. Long-term therapy with anti
      TBC drugs and steroids was started, achieving clinical and imaging improvement
      which retrospectively confirmed the diagnosis. Although with less amplitude,
      tremor persisted but a complete disappearance of focal dystonia was observed. The
      pathogenesis of both abnormal movements is particularly discussed since hand
      dystonia has never been mentioned in the literature as a consequence of brainstem
      damage.

PMID- 9646633
TI  - [Unilateral aplasia of the cerebellum in Aicardi's syndrome].
AB  - A case of unilateral aplasia of the cerebellum in a girl with Aicardi's syndrome
      is described. Aplasia of an entire hemisphere is one of the least frequent
      malformations of the cerebellum. Hypoplasia, partial hemispheric defects of the
      cerebellum and, rarely, complete absence of one hemisphere have been described in
      Aicardi's syndrome, which is associated with multiple systemic and CNS
      malformations. In our patient, who presented the characteristic trial of
      infantile spasms, callosal agenesia and retinal lacuna, we also saw right
      cerebellar aplasia along with other CNS malformations using magnetic resonance.
      We discuss the possibility that this aplasia arises as the result of a
      developmental defect of the posterior arterial system of Willis's polygon.

PMID- 9646634
TI  - [Comment on the letter to the editor: "Acute hydrocephalus and cerebral abscess
      in meningitis due to Listeria monocytogenes"].

PMID- 9646635
TI  - [Who should treat stroke].

PMID- 9646636
TI  - [Motor polyneuropathy due to massive ingestion of metronidazole].

PMID- 9646637
TI  - [Paralysis of the hypoglossal nerve in the presentation of dural arteriovenous
      fistula of the posterior fossa].

PMID- 9646638
TI  - [Migraine with episodic unilateral mydriasis: parasympathetic dysfunction or
      adrenergic hyperactivity?].

PMID- 9646639
TI  - Overview of the current status of PET in breast cancer imaging.
AB  - Present limitations of available procedures for the diagnosis of breast cancer
      have stimulated the development of new methods based on Positron Emission
      Tomography (PET). PET can be used to evaluate primary lesions, regionally
      metastatic and systemic metastases of breast cancer by use of tracers including
      15O-water 62Cu PTSM, [11C]L-methionine, [18F]fluordeoxyglucose and [18F]fluoro-17
      estradiol, for the assessment of blood flow, metabolism and receptor density. FDG
      PET is an excellent clinical method to detect primary breast lesions over 1 cm in
      diameter and to characterize such lesions. Several reports have also indicated
      various degrees of sensitivity and specificity of PET-FDG in detecting axillary
      lymph nodes. However, the precise role of PET in staging breast cancer remains to
      be defined in careful prospective studies. Prospective evaluation of PET during
      breast cancer chemohormonotherapy demonstrated a decline in FDG uptake in
      patients responsive to treatment, while no significant decline in FDG uptake is
      seen in the non-responding patients examined post initiation of treatment. PET
      may be useful when used in combination with other techniques of morphological
      imaging, for the proper characterization of hypermetabolic tissue. Additional
      studies including large populations with known or suspected breast cancer will
      enhance the clinical role of this technique for solving difficult diagnostic
      questions.

PMID- 9646640
TI  - PET imaging of breast cancer with fluorine-18 radiolabeled estrogens and
      progestins.
AB  - Through the use of fluorine-18 radiolabeled estrogen receptor ligands and
      Positron Emission Tomography (PET), imaging of estrogen receptor-positive (ER+)
      breast lesions has been accomplished. Targeting the estrogen and progesterone
      receptors found in receptor-positive breast cancer provides a means of diagnosing
      the disease non-invasively. The structure-activity relationship of evaluated
      fluorine-18 ligands are summarized and design considerations for construction of
      novel target ligands discussed. The role of the serum protein sex hormone-binding
      globulin (SHBG) in transport and metabolism of estrogens is related to target
      tissue uptake. A historical review of fluorine-18 radiolabeled estrogens includes
      the clinical study of 16 alpha-[18F]fluoroestradiol-17 beta (18FES) for imaging
      ER+ breast lesions. The success of 18FES in the clinical setting has shown the
      significance of PET in imaging primary and metastatic breast cancer by allowing
      for assessment of tumor response to tamoxifen therapy after as little as 7 days
      of treatment. Advantages of visualizing the tumor through targeting the
      progesterone receptor (PR) include PET imaging to follow the progress of
      tamoxifen therapy while the estrogen receptors are blocked. Clinical studies with
      the PR ligand 21-[18F]fluoro-16 alpha-ethyl-19-norprogesterone (18FENP) were not
      successful due to high hepatic uptake and poor correlation of tumor uptake with
      receptor content. Second generation PR ligands with decreased non-specific
      binding are predicted to be effective imaging agents for human PR+ breast cancer
      from studies in the immature rat and are ready for clinical evaluation.

PMID- 9646641
TI  - Somatostatin receptors and breast cancer.
AB  - The study of breast carcinogenesis is complicated by the heterogeneity of the
      disease. One way of simplifying is to subdivide these tumors into clinically
      relevant subgroups. There are indications that breast carcinomas, of which some
      express the somatostatin receptor (SS-R), can be divided this way. Expression of
      somatostatin receptors (SS-R's) in human primary breast cancer has a very high
      incidence. This can be demonstrated by in vitro autoradiography and in vivo by
      somatostatin receptor scintigraphy. However the clinical significance of
      somatostatin receptor expression in human breast cancer needs to be investigated.
      In this review article we summarize the current understanding of the functional
      role of somatostatin receptors in human breast cancer. Their relationship with
      neuroendocrine differentiation of the cancers and genetic and patient
      characteristics, the role of in vivo SS-R's visualization, and the possible
      medical and radiotherapeutic implications of these findings are discussed.

PMID- 9646642
TI  - Estrogen receptor scintigraphy.
AB  - Radio-labeled estrogen receptor ligands are tracers that can be used for
      functional receptor diagnosis. Their specificity towards receptors, together with
      the fact that only 50-70% of mammary carcinomas are receptor positive, renders
      them unsuitable for detection of primary tumors or metastases, and this means
      that estrogen receptor scintigraphy can be used neither for tumor screening nor
      for staging. However, both 18F-labeled and 123I-labeled estradiol derivatives are
      suitable for in vivo imaging of estrogen receptors. Their high specificity,
      established in animal experiments and in vitro studies has been reproduced in in
      vivo applications in humans. Tracers with positron radiation emitters are,
      however, hardly suitable for broad application owing to the short half-life of
      18F, which would mean that users would need to be situated close to a cyclotron
      and a correspondingly equipped radiochemical laboratory. The number of available
      PET scanners, on the other hand, has increased over the last few years,
      especially in Germany, so that this, at least, does not present a limiting
      factor. All the same, 123I-labeled estradiol derivatives will find more
      widespread application, since the number of gamma-cameras incorporating modern
      multi-head systems is several times greater. The results of studies with 123I-E2
      scintigraphy published to date are very promising, even given the initial
      technical problems mentioned above. As a method of examination, it could be
      optimised by using improved tracers with a higher tumor contrast and less
      disturbance from overlapping in diagnostically relevant locations, for instance,
      by selecting tracers with higher activities whose excretion is more renal than
      hepatobiliary. The use of modern multi-head camera systems can also be expected
      to improve the photon yield.

PMID- 9646643
TI  - Radioimmunolocalization of primary and metastatic breast cancer.
AB  - The appropriate therapy for breast cancer depends mainly upon early and reliable
      tumor detection, correct tumor staging and accurate re-staging after therapy.
      Current radiological imaging methods are based primarily on morphology resulting
      in high sensitivity but lacking specificity. Established nuclear medicine
      techniques are sensitive but not very specific. To improve specificity, a number
      of monoclonal antibodies, selected against a particular tumor-associated antigen
      expressed on the surface of breast cancer cells, have been radiolabeled for
      imaging in vivo tumor localizations. In theory, radioimmunodetection offers the
      potential to demonstrate cancer cells even in subradiological disease, or when
      anatomy-based imaging methods may be unable to distinguish the nature of an
      evident mass, making the differential diagnosis between an inflammatory reaction,
      a postsurgical fibrosis, or a truly viable tumor impossible. Suspected tumor
      recurrence indicated by increasing tumor marker levels could be another clinical
      indication for radioimmunolocalization, even if standard imaging modalities are
      negative. A large number of antibodies against different epitopes of human
      neoplastic breast tissue have been investigated previously. However, a highly
      specific and sensitive monoclonal antibody for immunoscintigraphy and
      radioimmunotherapy has not yet been found. This review addresses tumor-biological
      considerations, radioisotopes and radiolabeling methods, tumor targets and
      different monoclonal antibodies used for immunoscintigraphy (incl. SPECT amd PET)
      of breast cancer.

PMID- 9646644
TI  - Skeletal scintigraphy in breast cancer management.
AB  - Since its introduction in 1971 bone scintigraphy has become the classical
      procedure to confirm or exclude metastatic spread of breast cancer to skeleton.
      Recent developments in tomographic imaging (CT, MRI) as well as a more critical
      attitude towards technical diagnostic tests have raised the question about the
      present role of scintigraphy in staging and follow-up of breast cancer patients.
      Based upon systematic retrospective analyses bone scintigraphy is recommended for
      the initial staging of high risk patients (node-positive). In the follow-up of
      symptom-free patients bone scintigraphy did not prove to be necessary while it
      should be used in symptomatic patients to confirm and demonstrate the extent of
      metastatic disease. The bone scan is also useful for treatment control. However,
      due to similar findings in case of response (flare phenomenon) as well as tumor
      progression clinical relevance appears to be limited. In future increasing
      competition with CT and/or MRI will probably occur. Since MRI was proven to be
      more sensitive as well as specific in direct comparison, all efforts should be
      made to improve image quality and to reduce costs of skeletal scintigraphy. PET
      using F-18 fluoride might be an interesting alternative, if it becomes available
      for reasonable prices.

PMID- 9646645
TI  - Optimized sentinel node scintigraphy in breast cancer.
AB  - INTRODUCTION: Axillary lymph node dissection (ALND) represents an important
      staging procedure in the surgical treatment of breast cancer. However, it may
      result necessary in tumors of little dimensions because of low percentage of
      metastatic axillary lymph node (ALN). If a non invasive technique predicted the
      status of ALN, ALND procedures could be avoided. We carried out this study i) to
      establish the best technique to perform the lymphoscintigraphy for detecting the
      sentinel node in breast cancer and ii) to determine whether a clear sentinel node
      reliably predicts a disease free axilla. METHODS: 215 patients were submitted to
      the lymphoscintigraphy before surgery. Three different colloidal radiotracers
      with particle size ranging between < 50 and 1000 nm were injected sudermically or
      peritumorally. Early and late images were recorded in anterior and oblique
      projections and the SN was marked on the skin and biopsied using a gamma
      detection probe (GDP) during surgery. RESULTS: The SN was identified in 210/215
      cases (97.6%). The SN accurately predicted axillary ALN status in 204/210 (97.1%)
      patients in whom a sentinel node was identified and in all the cases (45
      patients) with tumor < 1.5 cm in diameter. In 38/101 cases with metastatic
      axillary nodes (37.7%) the only positive node was the SN. CONCLUSIONS:
      Lymphoscintigraphy can easily locate the SN in breast cancer. SN detection
      resulted easier when large size microcolloids were used. Subdermally
      administration appeared the best way of injection for palpable lesions. Breast
      cancer patients without clinical involvement of the axilla should undergo SN
      biopsy routinely and this may allow sparing complete axillary dissection when the
      SN is free of disease.

PMID- 9646646
TI  - Nuclear medicine approaches for detection of axillary lymph node metastases.
AB  - In breast cancer patients the detection of axillary lymph node involvement is a
      very critical issue, in view of the earlier diagnosis of the disease in recent
      years, and the increased frequency of very small tumors at first presentation.
      The size of cancer is related to the risk of axillary metastases, and this may
      affect the prognosis and the therapeutic strategies. Axillary lymph node
      involvement is generally recognized as an index of distant microdiffusion, and as
      it affects overall and disease-free survival, represents the basis for adoption
      of adjuvant chemotherapy. Routine axillary lymph node dissection (ALND) is
      expensive, and does not benefit about 70% of early breast cancer patients which
      are node negative (pN-). Today most of these patients have to sustain the
      potential morbidity and the economic costs of ALND. The clinical approach is
      known to be an unreliable diagnostic tool, and for the detection of axillary
      metastases, conventional X-ray techniques are also unable to solve the problem.
      By contrast, nuclear medicine procedures have revealed a very interesting
      diagnostic potential in recent years. This paper analyzes the numerous studies
      conducted in the field of lymph node visualization and the heterogeneity of the
      published experiences, taking into account the different approaches proposed in
      the literature: a) imaging with gamma-emitting tumor seeking agents; b)
      radioimmunoscintigraphy intravenous (i.v.) or by the interstitial route; c)
      lymphoscintigraphy with colloids and gamma probe sentinel biopsy; d) positron
      emission tomography (PET). Although it is very difficult to make a definitive
      statement about the clinical efficacy of all these methods, this paper reports
      the most important series of patients examined in the literature as well as the
      author's own experiences. This can serve as the basis for a better understanding
      of the potential of nuclear medicine procedures, and gives the reader the
      opportunity to weigh advantages and drawbacks of each method. At present,
      lymphoscintigraphy with gamma probe sentinel biopsy and FDG-PET are the nuclear
      medicine approaches with the best diagnostic performance. However, a correct
      comparison of the methods will not be possible, until their careful assessment in
      the same patients is performed. In addition, a final statement today should
      consider also the increasing need to carry out an economic analysis by evaluating
      the cost-effectiveness of the examinations.

PMID- 9646647
TI  - Impact of the diagnostic methods on the therapeutic strategies.
AB  - Over the last 25 years the diagnostic approaches and therapeutic strategies of
      breast cancer have dramatically changed. The relationship between diagnosis and
      therapy has gradually become more complex due to the ever more sophisticated
      diagnostic tools (mammographic screening, digital mammography, magnetic
      resonance, SPECT scan and FDG-PET), which have improved resolution limits and
      accuracy, and also due to the different therapeutic planning applied to breast
      cancer in these years (conservative surgery, neo-adjuvant chemotherapy, axillary
      dissection or not). Thus, in this paper, we have briefly analyzed the many open
      questions in breast cancer management and the clinical challenges of present
      diagnostic tools in relation to pre-, peri- and postoperative phases, and to
      therapeutic strategies in general. The main goal of mammographic screening is to
      detect early invasive cancers and to treat them at the first useful moment.
      However, at which age should one begin screening, and what is the impact on
      overall survival, the cost-effectiveness, and, most of all, the best operative
      approach to suspect lesions? Can digital mammography give a better quality of
      imaging with respect to conventional mammography? Does unexpected multicentricity
      and/or multifocality, which is sometimes showed by magnetic resonance, have any
      clinical relevance? Is this technique really better than traditional methods for
      the identification of local recurrence? Is scintimammography able to improve the
      low diagnostic accuracy of mammography on non-palpable breast lesions? Moreover,
      at present, the need for axillary dissection and its therapeutic and staging
      value is deeply debated: however, clinical detection of axillary metastases is
      not a reliable diagnostic tool and there are no conventional radiologic
      techniques to be used: recently nuclear medicine imaging has provided various
      approaches, such as SPECT scan with different tracers, FDG-PET, or
      lymphoscintigraphy with gamma probe sentinel biopsy: there are not only
      methodologic but also phylosophic differences in using these techniques. Neo
      adjuvant chemotherapy has allowed a dramatic reduction of primary breast cancer
      with a replanning of the surgical approach to large breast tumours but, at the
      same time, has posed new questions such as the adequacy of diagnostic pre- and
      perioperative revaluation. Finally, does postoperative follow-up take advantage
      of intensive diagnostic programs and are there therapeutic margins which would
      improve survival of patients with metastatic disease? This paper is an attempt to
      analyze the answers given in the literature. Nevertheless, at present, this
      matter is globally in progress and a scientific debate will provide, in the near
      future, a new promising scenario for breast cancer management.

PMID- 9646648
TI  - Neurogenesis in septum, amygdala and hippocampus in the marsupial brushtailed
      possum (Trichosurus vulpecula).
AB  - The times of origin of neurons in the septum, amygdala and hippocampus of the
      marsupial brushtailed possum, Trichosurus vulpecula, were determined with 3H
      thymidine autoradiography. The long time period for neurogenesis in the
      brushtailed possum facilitated analysis of neurogenetic gradients in the brain. A
      series of 20 possums were injected with 3H thymidine from postnatal (P) days 5-95
      and were allowed to survive until brain cytoarchitecture was mature. Our results
      indicate that septal neurogenesis was complete by P21 (38 days after conception)
      with a medial to lateral gradient of neurogenesis evident in the lateral septal
      division. Neurogenesis in the amygdala was complete in the basal, central and
      medial amygdaloid nuclei by P21, and in the lateral amygdaloid nucleus by P46,
      with a medial to lateral gradient of neurogenesis evident in basal, central and
      lateral amygdaloid nuclei. In the hippocampus, neurogenesis of pyramidal cells
      was complete in field CA3 by P50, and in field CA1 by P55. Early forming
      pyramidal cells (P5-12) were distributed adjacent to the stratum oriens in fields
      CA1 and CA3, with later forming pyramidal cells distributing in the middle of the
      stratum pyramidale (P21-32) and on the edge adjacent to the stratum radiatum
      (P46). Neurogenesis of dentate granule cells extended over a long period of time,
      from P5, at least until P82, with the earliest forming granule cells (P5-12)
      distributed adjacent to the stratum moleculare, and the latest forming granule
      cells (P82) adjacent to the hilus.

PMID- 9646649
TI  - [Peculiarities of pediatric anesthesia: premedication and inhalation induction].

PMID- 9646650
TI  - [Nasal ketamine compared with nasal midazolam in premedication in pediatrics].
AB  - OBJECTIVE: To compare the efficacy and side effects of midazolam and ketamine
      administered nasally for pediatric premedication. PATIENTS AND METHODS: In this
      double blind trial 60 children scheduled for elective surgery were randomly
      assigned to two groups to receive 0.25 mg.kg or 5 mg.kg nasal ketamine. We
      measured level of acceptance of medication, sedation, hemodynamic variables,
      reaction to separation from parents, side effects and time until recovery from
      anesthesia. RESULTS: The two groups were homogeneous. Acceptance of medication
      was good or adequate in all patients. The level of sedation was significant in
      both groups 10 min after premedication. Systolic arterial pressure was higher in
      the ketamine group 20 min after administration of the drug and upon arrival in
      the operating theater. Reaction to separation from parents was good in all
      groups. Secretions were higher in the ketamine group and hallucinations were
      experienced by three patients in the ketamine group and by two in the midazolam
      group. We found no difference in time until spontaneous eye opening after
      surgery. No complications were observed. CONCLUSIONS: The nasal route is
      adequately accepted by children. Both drugs are effective by this route and
      sedation is rapid. Time until postanesthetic recovery is similar with both drugs.
      The doses used have wide safety margins.

PMID- 9646651
TI  - [Comparative study of sevoflurane and nitrous oxide versus halothane and nitrous
      oxide in pediatric anesthesia: efficacy and hemodynamic characteristics during
      induction].
AB  - OBJECTIVES: To study the efficacy, side effects and hemodynamics of anesthetic
      induction in pediatric patients using sevoflurane and nitrous oxide or halothane
      and nitrous oxide. PATIENTS AND METHODS: We studied 80 pediatric ASA I-II
      patients aged between 1 and 10 years old scheduled for infraumbilical surgery of
      short duration. The patients were randomly assigned to two groups of 40 to
      receive one of the two drug combinations. All the children were premedicated with
      nasal midazolam 0.2 mg.kg-1. Induction was by inhalation of increasing
      concentrations of sevoflurane or halothane. The maximum inspired concentration
      during induction was 7% for sevoflurane and 3% for halothane. We analyzed
      induction time, side effects and hemodynamic variables. RESULTS: The induction
      time was 2.06 +/- 0.5 min for halothane and 1.6 +/- 0.6 min for sevoflurane (p <
      0.01). We observed no differences between the groups in coughing, laryngospasm,
      bronchospasm, secretions, apnea, nausea, vomiting, agitation or hiccoughing.
      Supraventricular beats appeared in 22.5% of patients in the halothane group and
      in 5% of the sevoflurane group. Induction with both anesthetics caused
      significant decreases from baseline blood pressure levels but no significant
      changes in heart rate. CONCLUSIONS: Inhaled sevoflurane in 60% nitrous oxide
      provides rapid but gentle anesthetic induction, with hemodynamic stability and a
      low incidence of airway complications. Sevoflurane is therefore a reasonable
      alternative to halothane for pediatric surgery.

PMID- 9646652
TI  - [Preoperative information and informed consent in surgically treated patients].
AB  - OBJECTIVE: Providing information is an important part of the doctor-patient
      relationship. In hospital practice today, patients and/or their families are
      sometimes given seriously inadequate information. Our aim was to analyze the
      quality of information received by patients before anesthesia and surgery.
      PATIENTS AND METHODS: The opinion of 300 patients (141 men and 159 women) at
      Hospital Universitario "Virgen de la Arrixaca" (Murcia, Spain) was studied from
      1993 to 1995. The sample was a stratified random one with sex and age as the
      classifying variables. Surgery was scheduled in 150 cases and emergency in 150.
      Mean age was 42.88 +/- 1.20 years (SD = 20.84; range 3-90 years). RESULTS:
      Patients were unfamiliar with risks of surgery and anesthesia in 19% and 18.3% of
      the cases, respectively. No information was received by 69.3% of patients
      regarding surgical risks and an even higher 75% of patients received no
      information on risks of anesthesia. In 3.6% of scheduled operations, neither
      patient nor family members were required to sign a consent from, though these
      cases involved patients under 18 years of age. For emergency surgery this
      percentage was 5.4%. Lack-of-information percentages are higher in operations
      requiring local or regional anesthesia. CONCLUSIONS: We must underline the poor
      quality of patient knowledge about medical procedures and the scarce information
      provided. Even fewer patients known about the risks of anesthesia. A patient's
      signing of an informed consent form does not correspond to real knowledge of the
      risks involved in the procedure.

PMID- 9646653
TI  - [Relationship between mixed venous saturation and cardiac index, hemoglobin and
      oxygen consumption in aortic surgery].
AB  - OBJECTIVE: Mixed venous oxygen saturation (SvO2) depends mainly on four
      variables: cardiac index (CI), hemoglobin concentration (Hb), arterial oxygen
      saturation (SpO2) and oxygen consumption (VO2). Our aim was to study the
      correlation between each of these variables and SvO2 during abdominal aortic
      surgery, a situation which is of special interest because of associated
      hemodynamic and metabolic variations and the high risk of cardiovascular events.
      PATIENTS AND METHODS: Twelve patients undergoing intrarenal aortic surgery were
      monitored by pulmonary artery catheter (Opticath), pulse oximetry and indirect
      calorimetry (Deltatrac Metabolic Monitor). SvO2, CI (measured by thermodilution),
      SpO2 and VO2 at six moments: post-induction (baseline), 1 min before and 1 min
      after clamping (pre-C, post-C), 1 min (post-D) and 10 min after declamping and at
      the end of the surgery. Hemoglobin concentration was measured at all moments
      except 10 min after declamping. RESULTS: All variables except SpO2 varied
      significantly (p < 0.001) during the study. SvO2 was associated with CI at all
      moments except post-D and at the end of surgery. Hemoglobin concentration was
      related to SvO2 at baseline and post-C. We found no correlation between SvO2 and
      VO2 or SpO2 at any moment. CONCLUSION: Monitoring SvO2 in patients undergoing
      aortic surgery is useful for detecting potentially prejudicial variations in
      cardiac output or hemoglobin concentration.

PMID- 9646654
TI  - [Anatomic basis of continuous axillary block of the brachial plexus with thoracic
      reservoir].
AB  - Although continuous axillary block is effective for periods of up to four to six
      weeks, pain clinic patients with severe chronic pain in the upper extremities,
      mainly resulting from neuropathic disease, can require continuous drug delivery
      by catheter-reservoir for up to three months or longer. We studied possible
      locations for implanting reservoirs or catheters from the perivascular axillary
      space in fresh cadavers, checking for possible vascular or nerve damage after
      applying the usual technique for reservoir implantation. The ideal location for
      the reservoir is the subcutaneous tissue of the homolateral infraclavicular space
      of the anterior side of the thorax. The customary procedures for inserting the
      catheter along the subcutaneous route that extends from the perivascular axillary
      space to the reservoir carry no risk of damaging vascular or nerve structures.

PMID- 9646655
TI  - [Thoracic epidural analgesia in the postoperative period of pediatric surgery for
      the repair of pectus excavatum and pectus carinatum].
AB  - To assess thoracic analgesia by continuous infusion in surgery to repair pectus
      excavatum and carinatum in children. This prospective study enrolled 14 children
      aged 6 to 14 years old scheduled for surgery to correct pectus excavatum and
      carinatum. After induction of general anesthesia, the T8-T9 epidural space was
      accessed and a catheter was inserted to T3-T7 with radioscopic monitoring. A
      loading dose of 0.03-0.04 ml/kg per segment to be blocked (5 segments: T3-T8) of
      0.125% bupivacaine and 3 micrograms/ml fentanyl was given to children under 7
      years of age; a dose of 0.02-0.03 ml/kg per segment was administered to children
      over the age of 7 years. A continuous perfusion of 0.1-0.4 ml/kg/h was
      maintained, with the possibility of additional boluses of 1 ml at 20 min
      intervals during surgery and the first three days thereafter. An intraoperative
      bolus was given when the level of blockade was not reached or when mean blood
      pressure and heart rate increased 15% over baseline. Pain relief was assessed on
      a numerical scale of 0 to 5 or on a scale of facial icons, depending on the
      patient's age. During the postoperative period, the pediatric ICU nurse
      administered a bolus if pain was [symbol see text]3 or heart rate increased 75%
      over age-based reference values. Top-up analgesia was provided with Metamizole at
      a dose of 25 mg/kg. No complications attributable to the technique or to
      sympathetic blockade were observed. All tubes were removed in the operating room.
      The thoracic epidural catheter was left in place for 70.3 +/- 2.6 h. Mean initial
      doses of analgesia were 0.45 microgram/kg of fentanyl and 0.2 mg/kg of
      bupivacaine. The mean number of complementary boluses was 3 +/- 1 during surgery,
      5 +/- 2 on the first postoperative day and 4 +/- 1 on the second day. No patient
      required top-up analgesia on the third day. Hemodynamic stability during surgery
      and the postoperative period was good. Analgesia was excellent (< 2) for 78.5% of
      the patients on the first day after surgery, for 85.7% on the second day and for
      all patients on the third day. We recorded one case of pruritus (7.1%), three of
      nausea (21.4%) that subsided when butorphanol was given epidurally (20
      micrograms/kg), and two cases of light sedation. Thoracic epidural analgesia is
      effective for alleviating postoperative pain from corrective thoracic surgery in
      children. Side effects were minimal and no anesthetic complications were
      observed.

PMID- 9646656
TI  - [Epidural abscess secondary to the implantation of a thoracic catheter].
AB  - Spinal compression related to the formation of an epidural abscess after epidural
      blockade is a rare but serious complication. We report the case of a male patient
      in whom a thoracic epidural catheter was implanted to provide analgesia after
      trauma involving fracture ribs. The patient developed an epidural abscess within
      one week of implantation. Delay in diagnosis led to persistent neurogenic bladder
      symptoms in spite of aggressive treatment. We review causal factors, mechanisms
      of formation, pathogenesis, diagnosis and management, as well as possible
      relation between injury and abscess formation. We also emphasize the importance
      of adequate vigilance as well as rapid diagnosis and adoption of therapeutic
      measures in order to avoid permanent sequelae such as paresis, sensory deficits
      or mechanical sphincter dysfunction.

PMID- 9646657
TI  - [Esophageal perforation caused by barotrauma].

PMID- 9646658
TI  - [Accidental overdose of caudal morphine chloride].

PMID- 9646659
TI  - [Thoracic epidural anesthesia for radical mastectomy in a female patient with
      multiple disorders].

PMID- 9646660
TI  - [Pneumothorax during laparoscopic Nissen fundoplication].

PMID- 9646661
TI  - [Blockade of the popliteal space. Response of the authors].

PMID- 9646662
TI  - [Effect of mivacurium in patients chronically treated with anticonvulsant
      agents].

PMID- 9646663
TI  - [Surveys as scientific instruments].

PMID- 9646664
TI  - [Analysis of the current status of neuroanesthesia in Spain using a national
      survey].
AB  - OBJECTIVES: Advances in complementary diagnostic explorations, surgical support
      technology and the complexity of neurophysiological monitoring require
      anesthesiologists to acquire specific knowledge for dealing with neurosurgery. We
      aimed to study the implantation of new anesthetic-surgical techniques in the
      field of neurosurgery, and the state of neuroanesthesia as a subspecialty in
      Spain. MATERIAL AND METHODS: A 20-item postal questionnaire sent to
      anesthesiology department heads of Spanish hospitals with neurosurgery teams.
      RESULTS: We received responses from 62% of the hospitals surveyed. Of these, 69%
      performed stereotaxic surgery, 30% functional cerebral surgery (for Parkinson's
      disease and epilepsy) and 21% offered neuroendoscopy. In 38% of the hospitals
      cerebral metabolism was monitored (hemoglobin oxygen saturation in the jugular or
      regional cerebral oxygen saturation) and/or cerebral electrophysiology
      (electroencephalogram, evoked potentials) and in 23.8% flows and pressures were
      measured (transcranial precordial and/or tracheoesophageal Doppler).
      Anesthesiologists specializing in neurosurgery are present in 62% of the
      hospitals. Interventionist neuroradiology is performed in 57%. It was noteworthy
      that 14.3% do not regularly have an anesthesiologist present during such high
      risk procedures. CONCLUSIONS: Although most centers continue performing
      "classical" neurosurgery with standard monitoring, a substantial proportion of
      hospitals (38%) show evidence of advancing in anesthetic techniques for
      neurosurgery in Spain. Anesthesia for neurosurgery as a subspecialty is available
      in 62% of the responding hospitals.

PMID- 9646665
TI  - [Satisfaction with locoregional anesthesia in women who had undergone cesarean
      section].
AB  - OBJECTIVES: To compare satisfaction with local-regional and general anesthesia in
      women undergoing cesarean, the possible influence of time of evaluation and
      recall of the anesthesiologist. PATIENTS AND METHODS: Retrospective study
      performed in all women who delivered by cesarean in the 6 first months of 1997.
      The women were assigned to two groups according to type of anesthesia, local
      regional or general. Their satisfaction with anesthesia was evaluated by
      questionnaire 48 to 72 hours after surgery and two weeks after release. Most
      items required discrete-point answers, including a satisfaction of a scale of 0
      to 10. During the second interview we also evaluated satisfaction with the
      procedure and hospital in general, as well as recall of the anesthesiologist.
      Group homogeneity was based on demographic, sociocultural, obstetric and surgical
      variables. RESULTS: In a context of high satisfaction with anesthesia, 189 (76%)
      of the 247 women receiving local-regional anesthesia gave high evaluations to the
      anesthesia (8.90 +/- 1.5; mean: 10), compared with 58 (24%) of those receiving
      general anesthesia (8 +/- 2; mean 8.5) (p = 0.001). Both groups were homogeneous
      except for the distribution of emergencies, which occurred more often in those
      receiving general anesthesia (p < 0.001). Women who had received local-regional
      anesthesia expressed greater willingness to repeat or recommend the technique (p
      < 0.001). The highest score in this group was from women receiving intradural
      anesthesia along with fentanyl for local anesthesia, with significant differences
      only in comparison to epidural anesthesia. The differences in responses between
      the first and second interview were scarce. The hospital received a lower
      evaluation than did either anesthesia or surgery (p < 0.001). The
      anesthesiologist, who was less well recognized than the obstetrician was
      remembered better among women receiving local-regional anesthesia (p = 0.008).
      CONCLUSIONS: Local-regional anesthesia can improve levels of satisfaction over
      that of general anesthesia among women undergoing cesarean surgery, and
      contributes to maintaining recall of the anesthesiologist. These results may be
      related to the fact of being conscious during the birth of a child.

PMID- 9646666
TI  - [Indices of prediction of neurologic focality during carotid endarterectomy
      carried out under regional anesthesia].
AB  - OBJECTIVES: To examine the relations between the development of neurologic events
      and the following variables: degree of stenosis of the contralateral carotid
      artery, prior neurologic symptoms and stump pressure of the ipsilateral internal
      carotid artery in patients undergoing carotid endarterectomy under regional
      anesthesia. PATIENTS AND METHODS: We undertook a prospective study of 92 patients
      undergoing carotid endarterectomy with a blockade of the superficial and deep
      cervical plexus. Neurological integrity was assessed and internal carotid artery
      stump pressure was monitored. Contralateral carotid artery stenosis and
      neurologic disease present before surgery were studied. RESULTS: Neurologic
      events developed when the carotid artery was clamped in 9.7% of patients. Mean
      stump pressure was significantly lower in symptomatic patients (43 +/- 11 mmHg)
      than in asymptomatic patients (74.6 +/- 24 mmHg) (p < 0.001). Neurologic symptoms
      developed during clamping of the carotid in 27.2% of the patients with stump
      pressure less than or equal to 50 mmHg, but in only 4.2% of those with stump
      pressure surpassing 50 mmHg. Stump pressure was significantly lower in patients
      with contralateral carotid stenosis. The incidence of neurologic events during
      clamping was unrelated to contralateral carotid condition, however. Likewise,
      neurologic symptoms before surgery was also unrelated. In six of the nine
      patients with neurologic events, internal carotid stump pressure was less than or
      equal to 50 mmHg, indicating that the sensitivity of this parameter to the
      development of neurologic events in our series was 66%. CONCLUSIONS: Although
      internal carotid artery stump pressure identifies a subset of patients likely to
      have a higher incidence of neurologic events during carotid artery clamping, it
      can not be considered the only criterion for placement of an intraluminal shunt
      to prevent such events. The state of the contralateral carotid artery and
      preexisting neurologic symptoms are not objective screening criteria for
      identifying patients at high risk of neurologic events during carotid clamping.

PMID- 9646667
TI  - [Comparative study of recovery times and psychomotor function after anesthesia
      with desflurane or isoflurane].
AB  - OBJECTIVE: To compare recovery from anesthesia with desflurane and isoflurane by
      analyzing awakening and psychomotor function. PATIENTS AND METHODS: In this
      prospective study of 30 ASA I-II patients undergoing general or urologic surgery
      the following variables were assessed before surgery: confusion, fatigue,
      drowsiness, torpor and pain. The Steward and Trieger tests of psychomotor
      function were also applied. After induction and intubation, maintenance was with
      isoflurane (0.6 +/- 0.3%) or desflurane (3 +/- 1.5%) and 60% nitrous oxide with
      fresh gas at a rate of 1 l/min. After withdrawing the halogen and switching to an
      open circuit (10 l/min), we counted time until appearance of the first sign of
      awakening. Clinical variables and psychomotor function were assessed 5, 30, 60
      and 90 min later. RESULTS: The two groups were similar anthropometrically.
      Duration of anesthesia and surgery were also similar. Times until awakening, eye
      opening, extubation and orientation were shorter in the desflurane group. Scores
      for fatigue (5 min), confusion (5 and 30 min), motor incoordination (5 min) and
      drowsiness (5 and 30 min) were also more favorable in the desflurane group.
      Patients receiving desflurane also scored significantly better on the Trieger
      test at 30 and 60 min. CONCLUSIONS: Recovery times are shorter with desflurane
      than with isoflurane. Clinical variables are also more favorable with desflurane
      and psychomotor function returns more quickly during the first hour after
      anesthesia.

PMID- 9646668
TI  - [Urapidil in anesthesiology: pharmacology and indications].
AB  - This review aims to describe the pharmacological bases for using urapidil, a
      recently introduced hipotensor, and to survey the literature on its therapeutic
      possibilities. The anesthesiologist often sees hypertension during surgery and
      must apply hypotensive treatment to prevent complications. Urapidil works mainly
      by antagonizing postsynaptic alpha-1-adrenergic receptors and stimulating 5-HT1A
      receptors, a double mechanism that provides vasodilation with moderate decrease
      in blood pressure without reflex tachycardia. Adverse side effects are rare and
      clinically unimportant. Onset is rapid after intravenous administration and
      duration of action is short; dose can be easily adjusted based on response and
      patient requirements. While urapidil has been used successfully in a variety of
      diseases and surgical procedures, its pharmacological characteristics make it
      particularly useful in patients at high cardiovascular risk or undergoing
      neurosurgery, in which results are good. Although the oral form is not sold in
      Spain, it is used in other countries to treat chronic high blood pressure.
      Urapidil is a hypotensor with a wide range of indications (critical hypertension,
      prophylaxis for hypertensive peaks and treatment of hypertension during surgery)
      and few side effects.

PMID- 9646669
TI  - [Cortical blindess as symptom of pre-eclampsia].
AB  - Neurological complications during preeclampsia are not infrequent; the appearance
      of total blindness is rare, however. We report the case of a 32-year-old
      primipara with no outstanding history, who presented total loss of vision with no
      accompanying neurological symptoms during week 37 of the pregnancy. Effective
      early management of blood pressure to levels at which self-regulation of cerebral
      perfusion could be established allowed total recovery of vision 8 hours after
      admission to the intensive care recovery ward. Cranial computerized axial
      tomography (CAT) showed bilateral occipital subcortical edema that resolved after
      8 days. The patient was released 13 days after admission with no sequelae.

PMID- 9646670
TI  - [Pulmonary edema of neurogenic origin and transtentorial hernia during anesthesia
      induction in a child with ventriculoperitoneal shunt].
AB  - We report the case of a 12-year-old boy with a peritoneal ventricular shunt who
      developed acute pulmonary edema of neurogenic origin after laryngoscopy and
      orotracheal intubation. Such maneuvers in the presence of diminished intracranial
      distensibility caused transtentorial herniation. Delayed diagnosis led to death
      in spite of appropriate treatment of postoperative complications.

PMID- 9646671
TI  - [Anesthesia techniques in epidermolysis bullosa].
AB  - Epidermolysis bullosa encompasses a group of rare clinical profiles marked by the
      formation of bullae on the skin and mucosa as the result of slight mechanical
      trauma. The anesthesiologist must take certain safety measures to monitor the
      airway and must expect difficult venous access in patients with this disease. We
      report our experience in providing anesthesia by various techniques for plastic
      and maxillofacial surgery. Most anesthetic techniques can be considered safe if
      they are performed with care and attention to detail.

PMID- 9646672
TI  - [Anesthesiology journals in Internet].

PMID- 9646673
TI  - [Reduction of gas leaks from laryngeal masks with controlled ventilation].

PMID- 9646674
TI  - [A new case of acute pulmonary edema secondary to phenylephrine administered on
      the conjunctiva in cataract surgery].

PMID- 9646675
TI  - [Short-length subarachnoid anesthesia: which local anesthetic should be used?].

PMID- 9646676
TI  - Morphometric comparison of the density of the mesangial deposits in idiopathic
      IgA-nephropathy and Schoenlein-Henoch nephritis. An ultrastructural study.
AB  - The present investigations performed by means of image analysis system was
      undertaken to compare the electron-microscopic density of the mesangial deposits
      in IgA nephropathy (IgAN) and Shoenlein-Henoch nephritis (SHN), as well as to
      study whether this parameter could correlate with the clinical data. The results
      showed, that the mean values of the deposit area per mesangial area were similar
      in both IgAN and HSN groups. The correlation between electron-microscopic density
      of the deposits and hematuria were positive in both IgAN and HSN groups, but only
      in IgAN patients this relationship has reached statistical significance.

PMID- 9646677
TI  - The Kartagener syndrome--an electron microscopic studies of biopsied mucosa.
AB  - We studied 43 tissue samples taken from patients (16 male and 27 women) with
      clinical diagnosis of Kartagener's syndrome. The specimens were fixed and
      prepared for transmission electron microscopy. After preliminary light
      microscopic examination 23 cases were qualified for ultrastructural studies. We
      found abnormal number of cilia on the bronchial mucosa cells. The ciliary
      structure was abnormal. In several cases we observed lack of inner and/or outer
      dynein arms, abnormal location of central microtubules, and abnormal number of
      microtubular doublets. Other findings were as follows: replacement of ciliated
      cells by goblet ones, mucosal edema and inflammatory infiltrate.

PMID- 9646678
TI  - Ultrastructural evaluation of microcirculatory vessels in rheumatoid synovial
      membrane.
AB  - Since morphological lesions in microcirculatory vessels are often difficult to be
      found in the light microscope, the electron microscope investigations were
      performed on the synovial membrane biopsy specimens from 70 patients with
      rheumatoid arthritis (RA). Most common lesions referred to venules, capillaries
      and arterioles were swelling and proliferation of endothelial cells, adherence of
      lymphocytes, monocytes and neutrofiles to the endothelium, their margination and
      diapedesis. Also destructive changes in the endothelial cells, basement membrane
      thickening due to their multiplication and microthrombi were observed. Platelet
      aggregates, fibrin, fragments of desintegrated cells and deposits of
      granulofibrillary substance corresponding to fibrinoid necrosis were frequently
      seen. In 7 patients, lesions of this kind were found only in electronograms. It
      can be assumed that the evaluation of ultrastructural changes in the
      microcirculatory vessels may be of great significance as a complementary
      diagnostic examination in future determination of RA progression and further
      prognostication.

PMID- 9646679
TI  - Intermediate cells in chronic pancreatitis--ultrastructural observations.
AB  - Ultrastructural evaluation of the pancreas resected due to advanced chronic
      pancreatitis revealed the presence of numerous intermediate cells exhibiting both
      the morphologic features of the exocrine-acinar cell and those of the endocrine
      cell of Langerhans'islets in 3 out of 5 cases examined. The analysis of
      ultrastructural pictures showed a predominance of acinar-alpha, beta cells,
      although acinar-alpha and acinar-beta cells were also found. The role of an
      increases in the number of intermediate cells in chronic pancreatitis is not
      clear and requires further investigations.

PMID- 9646680
TI  - Primary intracranial malignant fibrous histiocytoma--ultrastructural study.
AB  - Malignant Fibrous Histiocytoma is the most common soft tissue sarcoma in adults
      with the majority of cases that occur in patients between 50-70 years and 64% of
      cases occurs in male. Most commonly it arises in extremities (lower 49% and upper
      19%), less often in the abdomen (16%) and very rare in head localization (3%)
      [5]. Typically macroscopically it is a multilobulated, gray-white, fleshy mass
      between 5-20 cm of diameter. In light microscopy this tumour has a highly
      variable morphologic pattern and manifests a broad range of histological
      appearance. It has been classified into the following subtypes: storiform
      pleomorphic, myxoid, giant cell, inflammatory and angiomatoid. The first two
      subtypes are more frequent than others. The aim of this report is to present the
      electronmicroscopic features of giant cell type of MFH localized in head.

PMID- 9646681
TI  - Ultrastructural evaluation of hepatocytes membranes and changes in cytosolic
      enzymes distribution in methanol intoxication.
AB  - Acute methanol intoxication causes metabolic and structural disturbances of liver
      cells. The aim of this paper, therefore, was to evaluate the ultrastructure of
      liver cells membrane and the amount of lipid peroxidation products, as well as
      the concentration of marker enzymes of liver damage (ALT and AST) in blood serum.
      The experiment was done on Wistar rats which once received intragastrically 6,0 g
      methanol/kg b.w. as a 50% solution. The animals were decapitated 6, 12 and 24 h
      and 2, 5 and 7 days after the methanol administration. The liver was evaluated
      under transmission electron microscope and lipid peroxidation products were
      determined in the liver homogenate. The serum ALT and AST activity were also
      assayed. The biochemical results indicate the increase in lipid peroxidation
      products. The consequence of this is probably the membrane liver cell damage
      visible in the electron microscope.

PMID- 9646682
TI  - Ultrastructural evaluation of lysosomes and biochemical changes in cathepsin D
      distribution in hepatocytes in methanol intoxication.
AB  - Methanol oxidation is accompanied by free radicals and formaldehyde formation. It
      is likely to cause damage of lysosomal membranes. Lysosomal ultrastructure under
      transmission electron microscope and biochemical localization of cathepsin D were
      estimated after rats intoxication with methanol. The examination was carried out
      6, 12 and 24 h and 2.5 and 7 days after intoxication. Ultrastructural examination
      showed that methanol causes extension of Golgi apparatus cisterns and an increase
      in a number of lysosomes. From 12 h to 2 days lysosomes were characterized by
      damage of structure of membrane enclosing lysosomes. During the first days of
      intoxication activity of cathepsin D decreased in lysosomes and increased in
      cytosol. These changes may lead to uncontrolled extralysosomal proteolysis in the
      liver cells and to the onset of liver tissue destruction.

PMID- 9646683
TI  - The influence of partial gastrectomy on the ultrastructural changes in the liver-
      an experimental animal model.
AB  - The aim of our studies was to evaluate the ultrastructural changes in the liver
      in rats after partial gastrectomy. The studied group consisted of 19 Wistar
      strain rats. In 15 animals partial gastrectomy was done. The control group
      underwent laparotomy, only. All tissue material was fixed and then prepared in a
      routinous way for histological and electron microscopy studies. During
      histological examinations no abnormalities were found. On the ultrastructural
      level (in tissue samples taken from animals, no more then 4 months after
      gastrectomy) we found mitochondrial degeneration, vacuolization of cytoplasm,
      abnormalities in the nuclei and increased activity of B-K cells. The focal
      necrosis of the hepatocytes was also observed. In tissue samples from animals
      after 4 to 12 months after primary operation we found increasing number and size
      of lipid vacuoles in the cytoplasm of hepatocytes The number of Ito cells
      increased, also. The gastrectomy caused only minimal ultrastructural changes in
      the liver tissue within the period of observation. Those changes described above
      may result from numerous metabolic derangements found after gastrectomy.

PMID- 9646684
TI  - Ultrastructural studies of the effect of pentoxyfylline on the hepatic cell of
      the rat with simultaneous administration of cyclophosphamide.
AB  - Ultrastructural examinations carried out on liver specimens collected from Wistar
      rats revealed that single administration of cyclophosphamide in a dose of 150
      mg/kg body weight produced changes in the cytoplasmic structures, particularly in
      the smooth endoplasmic reticulum and mitochondria. The changes were reversible
      and subsided 14 days following cyclophosphamide administration. Administration of
      pentoxyfylline to rats in a dose of 30 mg/kg b.w./day for 10 days induced
      structural alterations in the intracytoplasmic structures of hepatocytes, similar
      to those caused by cyclophosphamide, although more intensified in the vicinity of
      the vascular pole. The pentoxyfylline-induced changes in hepatocytes retreated
      already 4 days after its withdrawal and can be considered adaptative.
      Simultaneous administration of both drugs to rats resulted in enhanced metabolic
      disturbances in hepatocytes and dissociation of adaptative mechanisms manifesting
      themselves in irreversible morphological changes in the intracytoplasmic
      structures and in the occurrence of collagen in the intercellular spaces.

PMID- 9646685
TI  - Cyclophosphamide in diffuse lung damage.
AB  - Some cyclophosphamide toxic effects on lung tissue are presented.
      Cyclophosphamide metabolism, pathogenesis of lung damage and morphological lung
      tissue changes caused by that agent were characterized. Attention was focused on
      BAL evaluation as a useful method in the monitoring of lung tissue damage degree.

PMID- 9646686
TI  - Effects of pentoxifylline on some peripheral blood parameters and haemostasis in
      acute pulmonary tissue injury after cyclophosphamide.
AB  - Cyclophosphamide (CP) is one of the widely used cytostatic drugs, with a strong
      toxic influence on pulmonary tissue. Experimental works have shown that a single
      high dose of CP causes injury to all elements of the interalveolar septum,
      especially to the alveolar endothelial and epithelial cells. The aim of this work
      was to evaluate the influence of pentoxifylline (PTXF) (30 mg/kg b.w.) on the
      ultrastructure of lungs capillaries and blood cell count as well as plasma
      fibrinogen levels in Wistar rats after intraperitoneal injection of 150 mg/b.w.
      CP. We established that in the doses applied PTXF had no statistically
      significant influence on the number of leukocytes and erythrocytes determined in
      the left ventricular blood of rats receiving CP, while the number of white cells
      from animals given PTXF only was higher than in controls. There was a smaller
      decrease in the number of platelets (p < 0.05) and smaller reduction in
      fibrinogen level (p < 0.01) in the serum of PTXF-CP animals than in the CP group.
      The results obtained suggest a protective effect of PTXF on CP induced changes,
      which have been evidenced in some of the parameters examined. Ultrastructural
      examinations found the lungs to be the organ of extramedullary thrombocytopoiesis
      in CP-treated animals and revealed that platelet accumulation in the system of
      lung capillaries was a potential cause of the decrease observed in the number of
      blood platelets following CP administration.

PMID- 9646687
TI  - Cyclophosphamide-induced changes of serum angiotensin converting enzyme activity
      and pulmonary microvessels ultrastructure.
AB  - The effect of cyclophosphamide (CP) on the ultrastructure of the lung tissue and
      the activity of angiotensin converting enzyme (ACE) in serum was evaluated in
      rats. The animals were given cyclophosphamide (CP) in a single intraperitoneal
      dose of 150 mg/kg b.w. ACE activity was evaluated in the blood serum collected
      from the left ventricle of the heart using the spectrophometric method. In all
      time subgroups, the CP-receiving animals showed a decrease in ACE activity.
      Ultrastructural examinations of CP-treated animals revealed increased adhesion of
      neutrophiles and monocytes to the damage endothelium of the alveolar septa
      vessels and focally accumulation of the platelets.

PMID- 9646688
TI  - Microenvironment of Morris hepatoma 5123 metastases to the lungs--ultrastructural
      analysis of intratumour injections of rhTNF-alpha.
AB  - We analysed the effect of rhTNF-alpha on the development of Morris hepatoma 5123
      spontaneous metastases to the lungs of Buffalo rats. After intratumour
      administration of the cytokine the lungs were found to contain scarce metastatic
      foci. In precapillaries and capillaries neoplastic cells were single or in small
      clusters, without contact with endothelial cells. Endothelial cells showed high
      pinocytic activity and frequently tightly closed vascular lumen. The stroma of
      interalveolar septa and the capillary bed contained multiple eosinophils.
      Moreover, eosinophils, histiocytes and monocytes mixed with abundant collagen
      fibres were found on the margin of single small metastatic foci and among
      necrotic neoplastic cells.

PMID- 9646689
TI  - Ultrastructure of bone marrow megakaryocytes in experimental haemorrhagic shock
      in rats. I. Correlation between ultrastructure of MK nuclei and DNA ploidy.
AB  - The correlation was described between the ultrastructural picture and DNA mass
      content of MK nuclei in experimental haemorrhagic shock in rats. Significant
      disproportions were revealed between the morphological pictures and the ploidy of
      MK nuclei in the successive phases of the shock. Abnormalities of the maturation
      of marrow MK nuclei were found in the first hours of the shock, being most
      pronounced in the 24th hour.

PMID- 9646690
TI  - Ultrastructure of bone marrow megakaryocytes in experimental haemorrhagic shock
      in rats. II. Correlation between ultrastructure of MK cytoplasm and
      thrombopoiesis.
AB  - Ultrastructural evaluation was performed of the MK cytoplasm in the successive
      phases of experimental haemorrhagic shock in rats. Qualitative abnormalities were
      revealed in the intracytoplasmic structures of MK. Platelets in the circulating
      blood were evaluated. A correlation was found between the changes in the
      intracytoplasmic organelles and the number and biological activity of blood
      cells. The results obtained indicate significant disturbances in the functioning
      of the thrombopoietic system in experimental haemorrhagic shock, which are caused
      by alterations within the intracytoplasmic structures of MK and lead to platelet
      production from morphologically differentiated but functionally immature MK.

PMID- 9646691
TI  - A comparison of the peritoneal cell population of pregnant rabbits after LPS or
      TNF-alpha induced septic shock.
AB  - Septic shock is a catastrophic consequence of invasive infection. Unfortunately,
      recent advances in surgical and medical sciences have not significantly reduced
      the overall mortality from septic shock. Bacterial antigens stimulate a cascade
      of cytokine release; each cytokine helps the host to overcome infection, but
      their excessive production causes them to trigger events that lead to septic
      syndrome and shock. Tumour necrosis factor (TNF-alpha) has a pivotal role in
      orchestrating the events leading to septic shock. Intraperitoneal administration
      of certain substances can increase the number and phagocytic activity of cells,
      which reach naturally the site of infection. Activation of the immunity cells in
      the peritoneal cavity and their immunocompetence are found to be responsible for
      the organism protection against abdominal cavity infections. Macrophages,
      lymphocytes and granulocytes of low activity in the non-stimulated peritoneal
      cavity become significant due to the influence of numerous biologically active
      substances. This study was designed to determine the peritoneal response to local
      administration of LPS or TNF-alpha in the course of experimental septic shock.

PMID- 9646692
TI  - Morphometric and ultrastructural studies of the spinal sensory ganglia in the
      course of sciatic nerve regeneration in rats intoxicated with ethanol.
AB  - The aim of the study was to examine morphological changes in the spinal dorsal
      ganglia (from which sensory fibres of the sciatic nerve extend) in animals
      intoxicated with ethanol, in which the sciatic nerve was transected and then
      sutured. By means of morphometric methods using a computer system of picture
      analysis and in ultrastructural examinations it was found that ethanol
      administered to rats to drink for 3 months caused only slight morphological
      alterations in the sensory nerve cells of the spinal vertebral ganglia on the non
      operated side. However, ethanol or its metabolites destroyed the regenerating
      sensory nerve cells of the spinal vertebral ganglia of the transected and then
      sutured sciatic nerve.

PMID- 9646693
TI  - Vasa vasorum of blood and lymph vessels in the broad ligament of the sheep uterus
      analyzed by scanning electron microscopy.
AB  - The morphology of vasa vasorum of the blood and lymph vessels in the broad
      ligament of the uterus was examined in 12 adult ewes. The technique of vascular
      corrosion casts with the usage of Mercox resin allows multiple surveys of a three
      dimensional organization of vascular networks under a scanning electron
      microscope (SEM). The study was appended by tissue pieces dried by the critical
      point method for SEM and semi-thin sections stained with toluidyne blue for light
      microscopy. Vasa vasorum surrounded both the larger vessels and the lymph vessels
      emanating from the ovary and the uterus. Significant differences in location and
      intensity of vasa vasorum in blood vessels were observed. They were less
      developed in the first part of the ovarian and the uterine arteries than in their
      smaller branches. Significantly large, two- or even three-layer vasa vasorum
      surrounded the ovarian and the uterine branches of the ovarian artery as well as
      the ovarian veins in the area of mesovarium. In the other areas of the broad
      ligament of the uterus, arterial vessels of similar sizes usually had a single
      layer vasa vasorum. The lymph vessels leaving the ovary and uterus were
      surrounded by dense, although usually single-layed, microvascular network. The
      presence of vasa vasorum on relatively small blood and lymph vessels of the broad
      ligament of uterus indicates their particular functions that are probably
      connected with the estrous cycle or pregnancy and changes of blood flow rate
      entering the ovary and uterus. However, the presence of significantly developed,
      multi-layer vasa vasorum networks on only some of the blood vessels indicates
      that it is probably one of the vessels morphological adaptations to serve the
      counter-current transfer of biologically-active regulators in the area of the
      broad ligament of the sheep's uterus.

PMID- 9646694
TI  - Ultrastructural changes on the root surface in "pressure zone" after experimental
      movement of teeth in young rats fed a low calcium and vitamin D-deficient diet.
AB  - Dietary calcium and vitamin D-deficiency, as a potential biological factor in
      etiopathogenesis of root resorption occurring during orthodontic tooth movement,
      still remains controversial. The aim of the present investigation was to assess
      the ultrastructural changes on the surface of the root in "pressure zone" after
      orthodontic tooth movement in rats fed a low calcium and vitamin D-deficient
      diet. The studies were carried out on 20 young Wistar rats. The results from the
      scanning electron microscopic showed the increased root resorption in "pressure
      zone" after orthodontic tooth movement in rats fed a low calcium and vitamin D
      deficient diet.

PMID- 9646695
TI  - Ultrastructural changes of a tooth root in young rats fed a low calcium and
      vitamin D-deficient diet.
AB  - The aim of the investigation was to assess the ultrastructural changes of the
      roots of the teeth in young rats fed a low calcium and vitamin D-deficient diet.
      The studies were carried out on 20 young Wistar rats. The results of the scanning
      microscopic observations showed the increased cementolysis and decreased
      mineralization of cementum and dentin in rats fed a low calcium and vitamin D
      deficient diet. The results indicated that the hard tissues of the teeth, besides
      bony system, are also involved in calcium homeostasis in rat organism.

PMID- 9646696
TI  - Scanning electron microscopy of the influence of dietary calcium and vitamin D
      deficiency on periodontium in the adult rats.
AB  - Mandibular bone and teeth in test animals fed a low calcium and vitamin D
      deficient diet in comparison to control rats were examined by scanning electron
      microscope (SEM). The observations showed increased resorption of the mandibular
      bone, increased resorption and decreased mineralization of cementum in the test
      group. The study indicated that calcium and vitamin D-deficiency in adult rats is
      related with changes of the mandibular bone and teeth.

PMID- 9646697
TI  - Preliminary assessment of ultrastructural changes in muscle fibres of rabbits
      after electric stimulation.
AB  - Studies were carried out on the effect of lateral electric surface stimulation
      used to treat lateral idiopathic spinal curvature in children and youth upon
      ultrastructural changes in the muscles which take part in spine stabilization.
      The experiment was carried out for 3 months on 10 rabbits. It was found that this
      stimulation, performed for 9 hours daily for 3 months, resulted in both
      progressive and regressive changes. Deviations from a norm suggest that the
      stimulation process destroys the sensory part of the reflex arc and chronic
      destructure of motoric neuron. In addition to this, overstraining of the muscle
      fibres with work was reflected in fibre hypertrophy and changes in the
      mitochondria.

PMID- 9646698
TI  - Ultrastructural manifestation of pharmacologic inhibition of the activities of
      lipases and proteases in the cat carotid body.
AB  - This study is based on the premise that if a subcellular element of an organ
      performs an appreciable functional role, then its inhibition could influence the
      ultrastructural organization of the organ. We addressed this issue in the
      investigation on the carotid body, a chemosensory organ, by comparing the
      ultrastructure of its parenchyma in phenylmethylsulfonyl fluoride (PMSF)-injected
      cat with that of the normal cat. PMSF, an inhibitor of lipases and proteases,
      induced degenerative changes chiefly in subcellular components other than the
      neurosecretory and synaptic elements being associated with signal transduction.
      The study suggests that the inhibited enzymes might also have to do with the
      carotid body function.

PMID- 9646699
TI  - An immunohistochemical study on the postnatal changes in the C-terminal flanking
      peptide of neuropeptide Y (CPON)--positive nerve fibers in pineal gland of the
      pig.
AB  - Postnatal development of innervation of the porcine pineal gland by C-terminal
      flanking peptide of neuropeptide Y (CPON)-immunoreactive nerve fibers was
      examined using the immunohistochemical technique. CPON-positive nerve fibers
      appeared in the pineal gland of the new-born piglets and formed plexus in the
      capsula and connective tissue septa of the gland. The nerve terminals branched
      off from the plexus and penetrated into adjacent parenchyma. The number of nerve
      fibers immunoreactive to CPON in parenchyma is very low in new-born and 20-day
      old piglets. In 7-month-old pigs they created a dense network.

PMID- 9646700
TI  - Membrane bounded dense bodies (MBB) of the domestic pig pinealocytes--current
      state of knowledge.
AB  - The results of our former investigations concerning the pig pinealocyte
      organelles named membrane bounded dense bodies (MBB) have been summarized. The
      presence of MBB is the most conspicuous morphological feature of pinealocytes of
      genus Suidae. The relative volume of MBB in the cell bodies of pinealocytes in
      adult domestic pigs ranges from 8% to 16% of whole cytoplasm. On the basis of
      their morphology, membrane bounded bodies were divided into two main types: MBB-1
      and MBB-2. Dense bodies of MBB-1 type have various inner structure and are
      present both in perikaryons and processes of the pinealocytes. Dense bodies of
      MBB-2 type are characterised by regular, multilammellar structure and their
      presence is restricted to pinealocyte perikaryons. The origin and transformations
      of the MBB are enigmatic. The relative volume of dense bodies in the pig
      pinealocytes changes during postnatal development and under various physiological
      and experimental conditions. The system of dense bodies is controlled by
      sympathetic innervation and environmental light. Dense bodies are also influenced
      by changes in function of pituitary-gonadal axis in female pigs and by
      administration of melatonin. High number of the dense bodies in the pig
      pinealocytes, significant changes in their number and inner structure in various
      physiological and experimental conditions as well as their exocytosis from
      pinealocyte processes suggest that these structures are involved in secretory
      processes in the pig pinealocytes.

PMID- 9646701
TI  - Diurnal changes in the ultrastructure and volumes of nuclei in liver cells of
      Hemidactylus frenatus in variable lighting conditions.
AB  - The research was carried out on young, mature specimens of Hemidactylus frenatus.
      The diurnal changes in the nucleus ultrastructure, especially changes in the
      number of perichromatin granules (PG), were investigated. The results let us come
      to the conclusion that the number of PG distinctly changes in twenty four hours
      and shows a negative correlation with the nuclei volumes.

PMID- 9646702
TI  - Ultrastructure of the calcareous layer eggshell of the turtle Emys orbicularis
      (L.). Preliminary study.
AB  - The calcareous layer of Emys orbicularis eggshell was examined by scanning
      electron microscopy. The layer is composed of well distinguished shell units
      which consist of needle-like crystallites radiating outwards from the cores. The
      linear structures of the cores on the inner surface appear to be similar to those
      in the eggshell of Mauremys caspica. On the inner surface of shell units of eggs
      with dead embryos there are flat, conical depressions. This surface in specimens
      from unfertilized eggs is almost flat. It may suggest that a developing embryo
      derives calcium from the eggshell.

PMID- 9646703
TI  - Ultrastructure of premetamorphic taste organs of the Bombina variegata.
AB  - Ultrastructural studies of taste organs in tadpoles of Bombina variegata indicate
      that these are taste buds (TBs). They occur in the apical parts of papillae of
      the mouth cavity lining. Each taste bud consists of taste cells and supporting
      cells; no basal cells were found. In the sensory area of taste bud there are two
      types of sensory cells: cells with a tuft of short (approximately 1.5 m)
      microvilli and cells with a single, longer (up to 3.7 microns) process,
      definitely longer than in TBs of other studied species of Anura. Fairly often,
      twin TBs were observed.

PMID- 9646704
TI  - Ultrastructural changes of Candida albicans under influence of cyclosporin A.
AB  - The aim of this study was the assessment of influence of cyclosporin A on
      ultrastructural changes of Candida albicans in vitro. Strains of Candida albicans
      isolated from woman with chronic vulvovaginitis were used. At the first part of
      experiment MIC (minimal inhibitory concentration) of cyclosporin on Sabouraud
      medium was assessed. Control plates were also prepared. From plates with Candida
      albicans there was observed its visual growth, the yeasts were prepared for
      electron transmission microscopic examines. It was found that ultrastructural
      changes of Candida albicans cells in the presence of Cyclosporin A. In
      particular, the cell wall was thicker and deteriorated. The organelles were
      altered in varying degrees and autolysis was observed.

PMID- 9646705
TI  - Ultrastructural determination of the early stage of conversion from root
      primordia to shoot primordia in vitro cultures of Solanum lycopersicoides Dun.
AB  - The object of the research were in vitro cultures of root primordia and the early
      stage of conversion from root to shoot primordia cultures (ESCRS) of Solanum
      lycopersicoides Dun. The cell ultrastructure of both culture types was studied in
      order to determine processes underlying the root and shoot morphogenesis type. It
      was found that a change of a morphogenesis type occurs together with
      reorganization of aggregate structure and the cell ultrastructural organization.
      There were 4 zones detected in root primordia culture aggregates (the surface,
      the starch, the division and the differentiation zone) and 3 zones in ESCRS
      culture aggregates (the surface, the inner and the differentiation zone). The
      differences were observed also in storage substances accumulated in a culture
      (starch in root primordia cultures; proteins, lipids and starch in ESCRS ones).

PMID- 9646706
TI  - Intermediate cells in the rat pancreas after chronic exposure to lead.
AB  - Ultrastructural analysis of the rat pancreas following the long-term exposure to
      lead revealed the presence of numerous intermediate cells in animals receiving
      lead acetate in doses of 500 ppm and 1000 ppm for 4 and 6 weeks. The cells
      included acinar-beta, beta-acinar and intermediate cells containing two kinds of
      endocrine granules- alpha and beta, and zymogen granules.

PMID- 9646707
TI  - [Classification of distal radius fractures--comparison of spiral CT with
      conventional roentgen image].

PMID- 9646708
TI  - [Multifocal malignant gastrinoma in MEN-I syndrome].

PMID- 9646709
TI  - [Intestinal imaging: 1997 literature update].

PMID- 9646710
TI  - [Value of double-contrast imaging of the small intestine in diagnosis of
      symptomatic jejunal diverticulosis].

PMID- 9646711
TI  - [Gas in the portal vein system].

PMID- 9646712
TI  - [Radiologically detectable changes in the radial annular ligament and the
      supinator muscle of the domestic cat (Felis catus)].
AB  - Elbow joints of a random sample of 59 cats were investigated by means of X-rays
      and dissection as well as histologically and by making cuts through synthetic
      resin-embedded joints. Bone-dense shadow craniolateral to the elbow joint was
      observed in X-ray images of 23 limbs (about 20%). Furthermore 8 of these 23 elbow
      joints (about 7%) showed signs of arthrotic alteration. Histologic examination
      revealed one or more centers of metaplasia of varying status of development of
      the annular ligament of the radius. Alterations varied from chondroid metaplasia
      to mineralisation and ossification. They turned out to be located in the area
      where the annular ligament of the radius crosses the tendon of origin of the
      supinator muscle and are considered to be a reaction of tough connective tissue
      to mechanical stress. Compressive forces seem to be less responsible than tensile
      stress. As soon as bone-dense shadow is observed in X-ray images, alterations
      have grown so far as the annular ligament of the radius as well as the tendon of
      origin of the supinator muscle are affected.

PMID- 9646713
TI  - [182 offspring of cows with bovine spongiform encephalopathy (BSE) in
      Switzerland. 1. Clinical findings].
AB  - This study involved 182 calves, heifers and cows that were the first generation
      progeny of cows with bovine spongiform encephalopathy (BSE). All animals
      underwent clinical and neurological examinations. Blood, milk, urine, ruminal
      fluid and cerebrospinal fluid samples were examined. Each cow underwent a
      specific examination for BSE which included assessment of behaviour, sensitivity
      and locomotion. This examination was performed twice, and there was very good
      agreement between the results. The most common symptom was nervousness (14
      animals). In the first examination, 68 animals were mildly to moderately
      sensitive to touching of the head, 44 animals were hypersensitive to a halogen
      light and 35 animals were hypersensitive to a camera flash. Twenty-four animals
      reacted by kicking when the hindlimbs were touched with a broom. None of the
      animals had disturbances in locomotion. Based on the interpretation of all
      findings and the comparison of the results of the first and second examinations,
      173 animals were diagnosed as free of BSE. In 9 animals, the disease could not be
      ruled out; however, it could not be confirmed in any of them. Histological and
      immunohistochemical examinations of the brain of all animals were negative for
      BSE (see Part 2 of the study for details). The results of this study indicate
      that abnormal clinical findings may occur in clinically healthy cattle. However,
      none of the progeny of cows with BSE exhibited clinical signs typical of BSE,
      such as disturbances in behaviour; sensitivity and locomotion.

PMID- 9646714
TI  - [182 offspring of cows with bovine spongiform encephalopathy (BSE) in
      Switzerland. 2. Epidemiology and pathological findings].
AB  - In order to detect lesions of a spongiform encephalopathy and/or accumulation of
      the protease resistant prion protein (PrPres), 182 offspring of cows affected
      with BSE were examined neuropathological and immunohistochemically. Neither
      spongiform encephalopathy nor PrPres accumulation were found. In seven animals
      other neuropathological lesions were seen, significant ones in three. Because of
      the small risk of exposure to contaminated feed in these animals, nearly all of
      which were born after the introduction of the protein feed ban for ruminants, the
      occurrence of spongiform encephalopathy in this series of BSE offspring would be
      suggestive of maternal transmission. However, the value of the study in this
      respect is quite limited. Only half of the animals were old enough to develop
      clinical and pathological evidence of the disease. If a maternal effect on the
      risk for the offspring is only to be expected during the last 6 months of the
      incubation of the dam as suggested by British investigations, only few animals in
      this study would fulfil the requirement of having been born during this critical
      period. Since it cannot be entirely excluded that the BSE agent transiently
      invades extraneural tissues in the early stages of infection, the above mentioned
      restriction to the final 6 months of the incubation time of the dam would not
      necessarily be applicable to all situations. We concluded that this study
      supports previous observations according to which maternal transmission of BSE is
      at best a rare event.

PMID- 9646715
TI  - [Is dirofilariasis in dogs spreading in south Switzerland?].
AB  - Microfilarial infections could be detected by the Difil Test in 11 (2.2%) of 479
      blood samples of clinically asymptomatic dogs from the South of Switzerland.
      Dirofilaria repens and D. immitis were identified in 3 (0.6%) and 8 dogs (1.6%),
      respectively, by the acid phosphatase activity of the microfilariae. 10 dogs with
      microfilaremia had been abroad or a stay outside Switzerland could not be
      excluded. One dog diagnosed with D. immitis could have had acquired the infection
      in the canton Tessin according to information given by the owner. Dogs with
      microfilaremia are a potential source of infection for mosquitoes. An indigenous
      cycle of infection in the South of Switzerland is possible since the mean average
      temperature in summer is above 18 degrees C which is necessary for optimal
      parasite development in the vector. A strict control of imported dogs or animals
      exposed to the disease in endemic regions as well as the therapy of infected dogs
      in the South of Switzerland is advisable.

PMID- 9646716
TI  - Farewell to old decency: the demise of handwritten medical records.

PMID- 9646717
TI  - Quetiapine: a new atypical antipsychotic.
AB  - Quetiapine has recently been approved for treatment of psychotic disorders. In
      short term (6 weeks) trials this atypical antipsychotic was shown to be as
      efficacious as the standard antipsychotics for the treatment of the positive
      symptoms of schizophrenia without causing any extrapyramidal symptoms or increase
      in the prolactin levels. Its efficacy for treating the negative symptoms was
      variable. Preliminary observations suggest its potential to improve the cognitive
      deficits of schizophrenia. It is metabolized by the p450 CYP 3A4 system with an
      estimated elimination half life of 6 hours. The optimal treatment is 300 mg to
      400 mg/day in two to three divided oral doses. The most common side effects
      include dizziness, hypotension, somnolence and weight gain. Changes in the ECG,
      the thyroid hormone and hepatic enzymes levels appear to be clinically
      insignificant. Quetiapine interacts with phenytoin, carbamazepine, barbiturates,
      rifampin and glucocorticoids; and coadministration with these drugs may require
      dosage adjustment. Doses need not be adjusted when fluoxetine, imipramine,
      haloperidol and resperidone are coadministered. Quetiapine may enhance the
      effects of antihypertensive agents and may antagonize those of levodopa and
      dopamine. Long term efficacy of quetiapine has not been determined. Also
      undetermined are its effectiveness for treating the first episode and treatment
      refractory schizophrenia. Data suggest that quetiapine may be used for the
      management of psychotic disorders in patients who may not tolerate the side
      effects of the typical antipsychotics and clozapine. It may also be helpful in
      patients whose psychotic manifestations did not adequately respond to risperidone
      and olanzapine.

PMID- 9646718
TI  - Vancomycin levels: to draw or not to draw.

PMID- 9646719
TI  - Cure of Goodpasture's disease.
AB  - Goodpasture's Disease is an explosive multisystem disease presenting initially as
      a pulmonary-renal syndrome. There is often little margin for error in making an
      early correct diagnosis to avoid respiratory and renal failure. Complications of
      invasive diagnostic testing and aggressive immunosuppressive treatment often lead
      to other organ dysfunction due to infection, hemodynamic disturbances, fluid and
      electrolyte challenges, and nutritional deficiency. Artificial organ therapy is
      often needed for pulmonary and renal support, for immunomodulation, and for
      nutritional replacement. The outcome is often considered satisfactory if the
      patient survives the acute presentation. Persistent organ failure is quite often
      the case, especially renal failure. Quality of life is often improved if there is
      subsequent renal transplantation. By then the patient may be considered "cured".
      Two cases are described below, contrasting young and elderly white females both
      in previous good health who developed rapid onset of Goodpasture's disease. One
      was cured after transplantation, and one was cured without transplantation. The
      severity of the renal involvement was the same for both patients. Cure of
      Goodpasture's Disease in the native kidneys is uncommon; a review of the
      literature is provided.

PMID- 9646720
TI  - Fetal growth and development.
AB  - The foetal growth is, for the greater part, determined genetically. There are,
      however, favouring and inhibiting factors, which influence this growth. In such a
      matter, the mother, the placenta and the foetus play an important part. The
      mother shows as well metabolic as vascular adaptations. The placenta must let
      through nutrients and oxygen; the uteroplacental circulation is characterized by
      a high flow, together with a low vascular resistance. The foetus itself plays an
      important part owing to its own growth factors. The principal growth factors are
      insulin and the growth factors analogous to insulin. The slowing up of the intra
      uterine growth is the consequence of genetic factors or of the decrease of the
      growth-potential. The real cause is, however, mostly a decrease of the vascular
      adaptation in the mother or a diminution of the uteroplacental circulation. The
      vascular causes usually induce an asymmetrical delay in the growth; foetal causes
      induce a symmetrical retardation. An exaggerated growth of the foetus--or
      macrosomy--is mostly due to an excessive inflow of nutrients: this is the case
      when a pregnant woman is suffering from diabetes. During the former years, it has
      become evident that abnormalities of the foetal growth influence the later life
      of people.

PMID- 9646721
TI  - New perspectives for the treatment of HIV infections.
AB  - Eleven compounds have now been licensed for the treatment of HIV (human
      immunodeficiency virus) infections: the nucleoside/nucleotide reverse
      transcriptase inhibitors (NRTIs) zidovudine (ZDV, AZT), didanosine (DDI),
      zalcitabine (DDC), stavudine (D4T) and lamivudine (3TC), the nonnucleoside
      reverse transcriptase inhibitors (NNRTIs) nevirapine and delavirdine, and the
      protease inhibitors saquinavir, ritonavir, indinavir and nelfinavir. Several
      other compounds that interact with the reverse transcriptase or protease or other
      targets of the viral replication cycle are in clinical or preclinical
      development. High expectations are vested in the acyclic nucleoside phosphonates
      PMEA and PMPA (which have proved clearly efficacious against HIV infections in
      phase II/III and phase I/II trials, respectively) and the bicyclam derivatives,
      which have recently been shown to block HIV infection through interference with
      the viral co-receptor CXCR4 (fusin). It has become increasingly clear that only
      the concomitant use of several anti-HIV agents combined can completely suppress
      HIV replication and offer the potential for a complete cure. To this end, the
      different compounds should be administered from the start at sufficiently high
      doses, and treatment should be started as soon as possible after the infection.
      Under these conditions, HIV-drug resistance development could be prevented, and
      progression to AIDS, arrested. Whether this procedure would also be able to
      eradicate the virus from the organism still needs to be proven.

PMID- 9646722
TI  - [Transport of drugs across the blood-brain barrier].
AB  - The blood-brain barrier prevents an indifferent medicine existing in the blood to
      enter also in the brain. This barrier has got an anatomical base: it is first
      consisting in a cerebrovascular layer of endothelial capillary vessels of the
      peripheral tissue. It is moreover covered by outgrowths of the flial cells, which
      are called astrocytes. There are, for that reason, important limits to a size of
      molecules which can reach the cerebral tissue through a paracellular way (through
      what is called in English "tight-junctions"). Most medicines must use the
      transcellular way. Lipophily is necessary to follow that way. Year after year, it
      appeared, thanks to a comparative study of the substances, that there exists-
      grosso modo--a positive correlation between the lipophilic level and the
      permeation-level of a substance in the cerebral tissue. There are, however,
      several exceptions: it is so that hydrophilic substances, possessing an important
      nourishing function (such as glucosis, amino-acids) seem to penetrate much more
      easily than we could expect when we consider their physicochemical
      characteristics. This is the result of the fact that there exist specifical
      transport-mechanisms for these substances at the level of the endothelial cell
      membranes, allowing the penetration of such substances. There exist, on the
      contrary, lipophilic components that penetrate the cerebral tissue much less
      strongly than we should expect. This happens because there also exist pumping
      mechanisms at the level of the hemato-encephalic barrier. The concerning
      substance, which was recently discovered is the "glycoprotein P", which is also
      responsible for the "multi-drug-resistance" and for the resistance of tumors to
      cytostatics. This phenomenon relies on a very efficient pumping of substances
      which have penetrated cells in which this protein expressed itself in the
      membranous structure. In order to obtain a better understanding of the function
      of the hemato-encephalic barrier, comprising the transport of medicines, it is
      most important to have reliable experimental models. It is to that aim that,
      during former years, the technique of cultivating endothelial cerebrovascular
      cells was developed. These cells are isolated from brains of calves or rats and,
      subsequently, cultivated on a laboratory medium; about a week later, they have
      grown a single and confluent layer. This layer represents a kint of "hemato
      encephalic barrier" in vitro, which allows us to study the transfer of substances
      through the layer and thus also the details concerning the transport mechanisms,
      as well as the factors influencing the permeability of the cells-layer (for
      instance the inflammatory stimuli). Concerning the "in vivo" research, the
      technique of intracerebral microdialysis in lab-animals proved to be very
      promising. In order to effect this microdialysis, a semipermeable microcannula is
      introduced in the brain tissue, across which an iso-osmotic liquid is being
      injected continuously. The substances staying in the interstitial liquid of the
      cerebral tissue will diffuse under the influence of a concentration gradient,
      into the dialysing liquid and they will also be ready to be analysed. Thanks to
      this technique, it is possible to follow, in the same animal, the evolution of
      the concentration in the brain of a substance which has, for instance been
      injected in a peripheral region. In this way, we obtain, indirectly and in vivo,
      informations about the functioning-process of the "hemato-encephalic barrier". We
      can, moreover, effect measures on a specific spot, for instance in tumoral brain
      tissue: this allows us to study the influence of specific transport-mechanisms.
      These rather recent techniques, as well in vitro as in vivo, will allow us, in
      consequence, to increase, during the next years, our understanding of the way the
      hemato-encephalic barrier functions as to the transfer of medicines towards the
      central nervous system. This understanding may lead us to new strategies allowing

PMID- 9646723
TI  - RNA editing: trypanosomes rewrite the genetic code.
AB  - The understanding of how genetic information is stored and expressed has advanced
      considerably since the "central dogma" asserted that genetic information flows
      from the nucleotide sequence of DNA to that of messenger RNA (mRNA) which in turn
      specifies the amino acid sequence of a protein. It was found that genetic
      information can be stored as RNA (e.g. in RNA viruses) and can flow from RNA to
      DNA by reverse transcriptase enzyme activity. In addition, some genes contain
      introns, nucleotide sequences that are removed from their RNA (by RNA splicing)
      and thus are not represented in the resultant protein. Furthermore, alternative
      splicing was found to produce variant proteins from a single gene. More recently,
      the study of trypanosome parasites revealed an unexpected and indeed counter
      intuitive genetic complexity. Genetic information for a single protein can be
      dispersed among several (DNA) genes in these organisms. One of these genes
      specifies an encrypted precursor mRNA that is converted to a functional mRNA by a
      process called RNA editing that inserts and deletes uridylate nucleotides. The
      sequence of the edited mRNA is specified by multiple small RNAs, named guide
      RNAs, (gRNAs) each of which is encoded in a separate gene. Thus, edited mRNA
      sequences are assembled from multiple genes by the transfer of information from
      one type of RNA to another. The existence of editing was surprising but has
      stimulated the discovery of other types of RNA editing. The Stuart laboratory has
      been exploring RNA editing in trypanosomes from the time of its discovery. They
      found dramatic differences between the mitochondrial gene sequences and those of
      the corresponding mRNAs, which indicated editing by the insertion and deletion of
      uridylates. Some editing was modest; simply eliminating shifts in sequence
      register of minimally extending the protein coding sequence. However, editing of
      many mRNAs was startingly extensive. The RNA sequence was essentially entirely
      remodeled with its sequence more the result of editing than the gene sequence.
      The identities of genes for such extensively edited RNA were not recognizable
      from the DNA sequence but they were readily identifiable from the edited mRNA
      sequence. Thus, despite the complex and extensive editing the resultant mRNA
      sequence is precise. Characterization of partially edited RNAs indicated that
      editing proceeds in the direction opposite to that used to specify the protein
      which reflects the use of the gRNAs. The numerous gRNAs that are used for editing
      are encoded in the DNA molecules whose role was previously a mystery. Using
      information gained in our earlier studies, the Stuart group developed an in vitro
      system that reproduces the fundamental process of editing in order to resolve the
      mechanism by which it occurs. They determined that editing entails a series of
      enzymatic steps rather than the mechanism used in RNA splicing. They also showed
      that chimeric gRNA-mRNA molecules are aberrant by-products of editing rather than
      intermediates in the process as had been proposed. Additional studies are
      exploring precisely how the number of added and deleted uridylates is specified
      by the gRNA. The Stuart laboratory showed that editing is performed by an
      aggregation of enzymes that catalyze the separate steps of editing. It also
      developed a method to purify this multimolecule complex that contains several,
      perhaps tens of, proteins. This will allow the study of its composition and the
      functions of its component parts. Indeed, the gene for one component has been
      identified and its detailed characterization begun. These studies are developing
      tools to explore related processes. An early finding in the lab was that the
      various mRNAs are differentially edited during the life cycle of the parasite.
      The pattern of this editing indicates that editing serves to regulate the
      alternation between two modes of energy generation. This regulation is
      coordinated with other events that are occurring during the life c

PMID- 9646724
TI  - Adaptation and information in ontogenesis and phylogenesis. Increase of
      complexity and efficiency.
AB  - Adaptations during phylogenesis or ontogenesis can occur either by maintaining
      constant or by increasing the informational content of the organism. In the
      former case the increasing adaptations to external perturbation are achieved by
      increasing the rate of genome replication; the increased amount of DNA reflects
      an increase of total but not of law informational content. In the latter case the
      adaptations are achieved by either istructionist or evolutionary mechanism or a
      combination of both. Evolutionary adaptations occur during ontogenesis mainly in
      the brain-mind, immunological and receptor systems and involve a repertoire of
      receptors that are., clonally distributed, genome-conditioned and amplified by
      somatic mutation. Specificity and intensity of responses are achieved a
      posteriori as a result of natural selection of the clones. The major adaptations
      during phylogenesis are accompanied by increased complexity. They have been
      attributed to shifts, short in time and space, against the entropic drive and
      thus occur notwithstanding the entropic drive and the second law of
      thermodynamics. The alternative view, is that the generation of complexity is due
      to the second law of thermodynamics in its extended formulation which includes
      Prigogine's theorem of minimum entropy production. This view requires however
      that natural selection provides the biological system with structures that bring
      the reactions within Onsager's range. The hierarchical organization of the
      natural world thus reflects a stratified thermodynamic stability. As the
      evolutionary adaptations generate new information they may be assimilated to
      Maxwell demon type of processes.

PMID- 9646725
TI  - The public science of Louis Pasteur: the experiment on anthrax vaccine in the
      popular press of the time.
AB  - The paper focuses on Pasteur's public experimentation of the anthrax vaccine
      (Pouilly-le-Fort, 1881) as portrayed in the English and French popular press of
      the time. It is argued that this 'popular' level of representation did not merely
      provide additional publicity for Pasteur's ideas. Rather, the nature and meaning
      of the experiment itself and of the related controversy on immunisation were
      substantially negotiated and shaped within the public arena. The multifold
      consequences of this framing at the public level are explored. In particular,
      attention is drawn to the relationships that in such process were established
      with other issues debated at the same time in the arena, namely homeopathy,
      vivisection and vaccination.

PMID- 9646727
TI  - Tufte, perception and visual representation: some bio-social context.

PMID- 9646726
TI  - The discovery of Chagas' disease and the formation of the early Chagas' disease
      concept.
AB  - This paper attempts to show how leading contemporary disciplines influenced the
      discovery of Chagas' disease and the formation of the early disease concept.
      Chagas was among the first generation of Brazilian trained scientists who
      incorporated modern principles of tropical medicine in its research. Thus, Chagas
      was familiar with characteristics of vector borne tropical diseases such as
      malaria and yellow fever. The detection of a hitherto unknown trypanosome in the
      gut of a reduviid bug prompted him to search for a related vector borne disease.
      Among the disciplines that were influential on Chagas' discovery and early
      disease description were pathology, entomology and parasitology. Parasitology as
      a new discipline was of crucial importance to tropical medicine and had a
      political dimension in the context of colonial medicine. Hence, leading
      scientists in tropical medicine were located in European countries and in the
      United States of America. One of these was the German Schaudinn School of
      Protozoology. The early description of American Trypanosomiasis can also be seen
      as a reflection of the Schaudinn School of Protozoology which dominated Chagas'
      scientific orientation towards parasitology with regard to the interpretation of
      the observed phenomena of the life cycle and the morphology and biology of T.
      cruzi. The first Chagas' disease concept was based on research of the biology and
      entomology of the trypanosome and its vector as well as on pathological studies
      of fatal cases. This concept was characterized by a confusion of some of the
      chronic forms of the disease, as iodine deficiency and goitre were endemic in
      some rural regions in Brazil. Therefore, early concepts of the disease faced
      strong opposition and even raised doubts about its existence.

PMID- 9646728
TI  - Penmanship. Rx for errors.

PMID- 9646729
TI  - Hospital closings. Sometimes less is less.

PMID- 9646730
TI  - What they don't know hurts.

PMID- 9646731
TI  - Be it ever so jumbled.

PMID- 9646732
TI  - The right to appeal.
AB  - When health plans say no, most patients back off. Only a few states guarantee
      independent reviews for treatment denials, but politicians and activists want to
      change that. The right to redress is the flash point of a larger movement to
      mandate consumer rights under managed care.

PMID- 9646733
TI  - Sizing up the sickest.
AB  - It's lurking all the time: Clues about patients prone to costly medical crises
      are already sitting in your computer system. The past opens a window on the
      future--if only you can ID the most vulnerable and guard against their getting
      sick in the first place.

PMID- 9646734
TI  - Blue on Blues.
AB  - Activists and regulators won't let Blue Cross & Blue Shield plans forget their
      roots. In fact, when these historic not-for-profits announce intentions to merge
      with other Blues or go for-profit, states demand repayment for years of foregone
      taxes. Charity has become the spoiler, dashing deal after deal.

PMID- 9646735
TI  - Uneasy marks.
AB  - Germany earned a reputation as a European nirvana, marked by a booming job market
      and generous health and social programs. Now, thanks to the high costs of
      rebuilding the former East Germany and other factors, national health programs
      face cutbacks. But just about everyone has a stake in guarding the status quo.

PMID- 9646736
TI  - Finances. Kaiser's squeeze play.

PMID- 9646737
TI  - Consolidation. An emergent merger.

PMID- 9646738
TI  - Hospital pulse--October 1997.

PMID- 9646739
TI  - Software support. Hung up on response time.

PMID- 9646740
TI  - Cumulative trauma disorders of the upper extremity.

PMID- 9646741
TI  - Clinical lectures on scriveners' palsy, or the paralysis of writers. 1864.

PMID- 9646742
TI  - Nerve injury in repetitive motion disorders.
AB  - Nerve compression in repetitive motion disorders is being recognized with
      increasing frequency. The pathophysiology of chronic nerve compression spans a
      broad spectrum beginning with subperineurial edema and progressing to axonal
      degeneration. These changes depend on the amount and duration of the compressive
      forces. Certain postures or positions in the upper extremity will increase
      pressures around certain nerves increasing pressure exposure. Evaluation of these
      patients with chronic nerve compression should include examination at all levels
      of potential entrapment in the upper extremity to identify all sites of
      compression.

PMID- 9646743
TI  - Muscle injury in repetitive motion disorders.
AB  - Documentation of causality between repetitive motions and musculoskeletal
      disorders calls for detailed understanding of the exposure variables and the
      corresponding physiologic responses in the biologic tissues. Quantification of
      the kinetics in some jobs characterized by repetitive motions is summarized with
      the physiologic responses in the muscles. Muscle activity pattern was studied in
      different shoulder muscles or muscle parts, and in elbow and wrist flexor
      muscles. Activity pattern was dependent on the kinetics of the work requirements.
      This holds true for the compound electromyographic signal and for single motor
      units. Low threshold motor units have been identified that are recruited
      continuously, the so called Cinderella fibers. The physiologic consequences of
      prolonged muscle fiber activity are reviewed, revealing mechanisms for the
      development of necrotic changes in the muscle, which support the likelihood of
      work relatedness for musculoskeletal disorders.

PMID- 9646744
TI  - Structure and physiology of joints and their relationship to repetitive strain
      injuries.
AB  - Joints involved in repetitive strain injuries are diathrodial, that is, two bone
      ends with cartilaginous end plates sheathed by a soft envelope of synovium. The
      cartilaginous plates, consisting of chondrocytes, ground substance, and at least
      seven species of collagen, but mostly Type II, cushion the bone ends during
      repeated elastic compression and enable them to slide with minimal friction. The
      metabolic needs of the avascular cartilage are met by nutrients and waste
      products diffusing through the synovial fluid and into and out of the synovium
      and its blood vessels and lymphatics. Synovial nerves give joint position
      information. Fat, collagen, and glycosaminoglycans constitute the deformable
      synovial sheath. Synovial lining cells synthesize joint lubricants, matrix
      molecules, digestive enzymes, and cytokines, and participate in immunologic
      processes that can be reparative or degradative especially of cartilage. Heavy
      repeated forces applied to the upper and lower extremity joints cause
      degenerative changes that can be documented radiographically. Repeated light
      loading, such as in computer keyboard use, is evaluated inadequately with current
      imaging and clinical techniques. Differences in individual's response to
      repetitive loading may be caused by subtle differences in the interaction and
      initial conditions of the musculoskeletal structures, including the joint,
      involved in repetitive strain injuries.

PMID- 9646745
TI  - Risk factors for upper limb disorders. Implications for prevention and treatment.
AB  - Epidemiologic studies have revealed several associations between physical work
      load factors and some common upper limb disorders. In the treatment of a case of
      work related upper limb disorder, modifications of work that are feasible to be
      implemented in the field should be done as a first priority. Some case studies
      suggest notable effects of ergonomic measures on the occurrence of upper limb
      disorders. Economic analyses of individual workplace have indicated that the
      investments usually have a short payback period. In work related carpal tunnel
      syndrome, the physical demands of the job, especially the force demands of
      gripping, should be considered before deciding on surgery, because gripping force
      may return slowly after surgery, and may be compromised by the surgical procedure
      itself.

PMID- 9646746
TI  - Gender and neurogenic variables in tendon biology and repetitive motion
      disorders.
AB  - The incidence of repetitive motion disorders is increasing. Numerous studies have
      indicated that the incidence in females exceeds that in males. Some of the
      evidence regarding gender related factors in tendon biology is discussed and new
      data related to the regulation of gene expression in an animal model of tendon
      overuse, the determination of sex hormone receptors in tendons, and the influence
      of pregnancy associated factors on gene expression in four different tendons is
      provided. Furthermore, because neurogenic mechanisms may contribute to
      inflammatory conditions, new evidence is provided that supports the concept that
      neurotransmitters can influence expression of genes that could participate in
      such inflammation. By increasing our understanding of the regulation of tendon
      cellular and molecular biology, new approaches to preventing disease development
      and treatment of existing disease may evolve.

PMID- 9646747
TI  - Coping with arm pain in the workplace.
AB  - Regional arm pain is a ubiquitous, remittent, and intermittent predicament of
      life. There is no evidence that arm use in a fashion that is familiar and usually
      comfortable, inside or outside the workplace, increases the incidence of regional
      arm pain. Therefore, coping with this morbidity, not avoiding it, is prerequisite
      to healthfulness. When one systematically examines the reasons a worker may find
      coping prohibitive, task demands are not the common denominator. Psychosocial
      factors such as work organization and interpersonal relationships predominate.

PMID- 9646748
TI  - Australian repetition strain injury phenomenon.
AB  - The industrial upper limb pain epidemic colloquially known as repetition strain
      injury rapidly increased in the early 1980s to peak in 1985. Its less precipitous
      decline coincided with an awareness that repetition strain injury was a
      nonphysical sociopolitical phenomenon and a corresponding loss of the pecuniary
      benefits enjoyed by the powerful vested interest groups. Although its
      protagonists incorrectly claimed that this was a new disease, the rise and fall
      of repetition strain injury followed its historical predecessors including
      telegraphists' wrist and writer's cramp. Those affected by this phenomenon, a
      clearly defined cohort, were all employees who were highly suggestible and
      engaged in menial repetitious tasks with little job satisfaction. These patients
      were differentiated from those with genuine work related injuries whose symptoms
      are reproducible, with physical signs easily defined, disease identifiable, and
      response to physical treatment predictable. Most patients with repetition strain
      injury genuinely suffered the symptoms of which they complained and made little
      secondary gain relative to the protagonists of repetition strain injury who had a
      vested interest. The similarities between Australian repetition strain injury in
      the 1980s and American cumulative trauma disorder in the 1990s is compelling.

PMID- 9646749
TI  - Workers compensation. Effect of state law on treatment cost and work status.
AB  - Workers compensation legislation is regulated at a state level resulting in
      different benefits based on the state of employment. The negative effect of
      workers compensation on the results of surgical treatment has been established
      previously. A comparison of the results of treatment of patients receiving
      workers compensation from different states has not been reported. This study
      prospectively evaluated the effect of the difference in state workers
      compensation laws on the number of postoperative visits, amount of postoperative
      therapy, time off from work, and return to work status. The study group consisted
      of 275 patients. The results indicated a significant increase in the number of
      postoperative visits, amount of therapy, time off from work, and number of
      patients who remained out of work in the compensation versus the noncompensation
      group. A significant increase in these parameters also was present in the
      Pennsylvania compensation group as compared with the New Jersey compensation
      group. This study shows that differences in workers compensation benefits have a
      significant effect on the results of medical treatment, return to work status,
      and the cost of medical care.

PMID- 9646751
TI  - Cubital tunnel syndrome pathophysiology.
AB  - Cubital tunnel syndrome is the second most common peripheral compression
      neuropathy. The unique anatomic relationships of the ulnar nerve at the elbow
      place it at risk for injury. Normally with elbow range of motion, the ulnar nerve
      is subjected to compression, traction, and frictional forces. As the elbow is
      flexed the arcuate ligament elongates producing a decrease in canal volume of
      55%. Intraneural and extraneural pressures increase and have been shown to exceed
      200 mm Hg with elbow flexion and flexor carpi ulnaris contraction. Because the
      ulnar nerve courses behind the elbow axis of rotation, elbow flexion produces
      excursion of the nerve proximal and distal to the medial epicondyle. The ulnar
      nerve also elongates 4.7 to 8 mm with elbow flexion. Cubital tunnel syndrome may
      develop because of various factors including repetitive elbow motion, prolonged
      elbow flexion, or direct compression. An understanding of the anatomy and
      pathophysiology associated with cubital tunnel syndrome will aid in patient
      evaluation and determination of the appropriate treatment.

PMID- 9646750
TI  - Carpal tunnel syndrome as a repetitive motion disorder.
AB  - The incidence of repetitive motion disorders is increasing and in 1990 comprised
      48% of all reported workplace illnesses (up from 18% in 1980). Carpal tunnel
      syndrome is the most prevalent disease classified as a repetitive motion
      disorder, thus making its prevention and management an occupational health and
      safety priority. The clinical picture of carpal tunnel syndrome, pain and
      paresthesias on the palmar radial aspect of the hand, often worse at night,
      and/or exacerbated by repetitive, forceful use of the hand, is recognized
      readily. Carpal tunnel syndrome is a condition of middle aged people and most
      middle aged people work. It follows that more often than not carpal tunnel
      syndrome occurs in a work-place setting, and the extent to which the work
      contributes to the condition is of great interest regarding prevention and
      treatment. Some studies find little evidence supporting the concept of carpal
      tunnel syndrome as caused by work, whereas others propose that more than half of
      cases of carpal tunnel syndrome in workers may be attributed to workplace
      factors. It is explored whether the incidence, prevalence, and significance of
      carpal tunnel syndrome as a repetitive motion disorder is known.

PMID- 9646752
TI  - Impingement syndrome and rotator cuff disease as repetitive motion disorders.
AB  - The relationship between repetitive motion and subacromial impingement and
      rotator cuff disease is controversial and poorly understood. The potential
      etiology is multifactorial and involves patient related factors (age,
      supraspinatus outlet anatomy, and preexisting rotator cuff pathology) and worker
      related factors (arm position, lifting requirements, numbers of repetitions).
      Radiographic and magnetic resonance imaging abnormalities may represent
      preexisting disease that could have predisposed the patient to the development of
      impingement syndrome, but should be interpreted cautiously within the context of
      the remainder of the clinical picture. Treatment often involves temporary or
      permanent modifications of the work environment.

PMID- 9646753
TI  - Focal dystonia and repetitive motion disorders.
AB  - It commonly is observed that focal hand dystonias, such as writer's cramp or
      musician's cramp, are associated with repetitive movements, although definitive
      proof of a causal relationship is lacking. These focal dystonias are often task
      specific, with involuntary muscle contractions occurring only when patients
      perform specific acts such as writing or playing a musical instrument.
      Physiologic studies show deficiencies in spinal reciprocal inhibition and
      abnormalities of central sensory processing and motor output that may be related
      to reduced cortical inhibition. Recent studies in primates support the notion
      that repetitive motions can induce plasticity changes in the sensory cortex
      leading to degradation of topographic representations of the hand, and raise the
      possibility that sensory training may be beneficial. Current treatment options
      for focal dystonia include botulinum toxin injections, anticholinergics,
      baclofen, benzodiazepines, and occupational therapy.

PMID- 9646754
TI  - Cumulative trauma disorders and repetitive strain injuries. The future.
AB  - Cumulative trauma disorders account for 56% of all occupational injuries.
      Currently, occupational injuries affect 15% to 20% of all Americans. The United
      States government predicts that by the year 2000, 50% of the American workforce
      will have occupational injuries annually and 50 cents of every dollar will be
      spent on cumulative trauma disorders. There is common agreement on the need for
      reduction of cumulative trauma disorders in the workplace. However, there is
      little agreement on the appropriate definition for musculoskeletal pain that
      occurs in the workplace, or the ergonomic and epidemiologic model for cumulative
      trauma disorders, or on the specific exposure relationships of the individual, by
      the job, and occurring in the workplace. The previous treatments for, and the
      natural history of, cumulative trauma disorders in other countries gives some
      insight into the possible future of cumulative trauma disorders for the United
      States. Until research can provide specific dose and exposure relationships for
      the individual, prevention remains the best treatment for cumulative trauma
      disorders in the workplace.

PMID- 9646755
TI  - Debridement arthroplasty for osteoarthritis of the elbow.
AB  - For treatment of osteoarthritis of the elbow, the authors use debridement
      arthroplasty with a medial or lateral approach. Thirty-eight elbows in 36
      patients treated with this procedure were examined. The age of the patients
      ranged from 20 to 71 years, with a mean age of 41.7 years. Cubital tunnel
      syndrome was present in 16 of the 38 (42%) elbows. The operations were performed
      through a lateral approach in four elbows, a lateral approach with medial skin
      incision for ulnar nerve neurolysis in 16 elbows, a medial approach in 10 elbows,
      and a medial plus a lateral approach in eight elbows. The followup ranged from 2
      years to 12.1 years, with an average of 5.9 years. Complete pain relief or
      minimal elbow pain was reported in 95% of patients who had surgical treatment.
      The average gain in motion was 6 degrees extension and 18 degrees flexion.
      Results for the various surgical approaches did not show a statistically
      significant difference. Recurrence of bony spurs and ridges was analyzed
      additionally in 18 selected patients who could be observed more than 5 years
      after surgery (range, 5-12 years). Redevelopment of bony spurs on the coronoid
      process and olecranon tip occurred in all 18 patients, but those changes were
      graded as mild in 13 (74%) patients and moderate in five (16%) patients and were
      accompanied by no pain or slight pain. Elbow arthroplasty as used by the authors
      produces stable and reliable results for relief of pain, gains in range of
      motion, and the absence of recurrence of significant osteoarthritis.

PMID- 9646756
TI  - Patient satisfaction and function after primary and revision total hip
      replacement.
AB  - This study assessed and compared satisfaction and function before and after total
      hip replacement as reported by 531 patients who had primary and revision surgery
      and 1087 patients who had primary surgery only. All operations were registered by
      the Norwegian Arthroplasty Register during the years 1987 to 1993, with time from
      last surgery to followup ranging from 0.6 to 6.4 years. Sixty-one percent of the
      patients who underwent revision surgery and 84% of the patients who did not
      undergo revision surgery rated their overall satisfaction with the hip implant as
      good or very good. With adjustment for primary diagnosis, gender, age,
      bilaterality, and time since the primary operation, a substantial benefit of
      total hip replacement was observed in both groups with regard to pain, walking
      ability, and need of help. However, improvement was less among patients who
      underwent revision total hip replacement than among those who did not undergo
      revision surgery. A deterioration was seen among patients who underwent revision
      surgery with regard to employment status and exercise habits.

PMID- 9646757
TI  - Biomechanical effect and clinical application of the hip joint moment reduction
      brace.
AB  - A new brace, the hip joint moment reduction brace, has been designed and
      constructed. The basic construct of the brace incorporates only the thigh, and it
      minimally restricts one's activities of daily living. The concept of the brace is
      to reduce the frontal plane moment of the applied force against which the
      abductor muscle must contract to balance, and this reduction of the frontal plane
      moment results in reduction of the abductor muscle force. The brace uses the
      mechanism of the ischial weightbearing and lessens the abductor moment by
      transmitting load from the ischium through the condyle of the femur. In gait
      testing, the maximum ischial load taken up by the brace was 36.9% of the ground
      reaction force in the late stance phase, and the integrated electromyogram of the
      abductor muscle was reduced by 32.6% during the whole stance phase using this
      brace. These findings confirmed a reduction in the frontal plane moment of the
      hip joint and the potential for reduction in the load on the hip joint. The hip
      joint moment reduction brace is recommended as effective conservative management
      of hip disorders, such as coxarthrosis, that are caused or worsened by
      biomechanical insufficiency.

PMID- 9646758
TI  - Hemispheric titanium porous coated acetabular component without screw fixation.
AB  - One hundred fifteen hips in 108 patients with primary total hip arthroplasty
      using the anatomic porous replacement hemispheric acetabular component implanted
      without adjunctive screw fixation had a mean postoperative followup time of 6
      years (range, 5-7.4 years). Clinical evaluation was performed using the Harris
      hip score and patient self assessment using a modified Short Form-36
      questionnaire. Radiographs were measured for radiolucent lines, polyethylene
      wear, osteolysis, migration, and fractures. No acetabular metal shell had been
      revised for loosening or was radiographically loose with or without migration
      (more than 3 mm) at final followup. Reoperation was done in nine (8%) hips
      because of polyethylene insert wear or disassembly. No fracture of the acetabular
      bone occurred at the time of surgery or was observed on radiograph. Fixation of
      the metal shell was stable, with progressive radiolucent lines observed at final
      followup in 2% of the hips. Osteolysis was recorded in one patient with two
      acetabular components. The fixation of noncemented hemispheric porous coated
      acetabular components is more related to the technique of acetabular bone
      preparation and press fit implantation than to whether additional screws or peg
      fixation are used. Fixation of this acetabular component without screws at an
      average of 6 years after surgery is reproducible and predictable in primary hip
      arthroplasty. The design of modular polyethylene inserts has been improved and
      should reduce the wear rate of reoperations of the polyethylene insert.

PMID- 9646759
TI  - 3- to 11-year followup of occipitocervical fusion for rheumatoid arthritis.
AB  - The relief of myelopathy usually is unsatisfactory by a conventional Gallie type
      atlantoaxial fusion for patients with rheumatoid arthritis who have irreducible
      atlantoaxial dislocation. To accomplish a decompressive laminectomy of the atlas
      in the treatment of myelopathy, the authors have been performing a new surgical
      procedure since 1985 for occipitocervical fusion using a rectangular rod. The
      postoperative outcomes for 25 patients with rheumatoid arthritis were evaluated
      clinically and radiographically with a 3- to 11-year (mean, 6.5 years) followup.
      A decompressive laminectomy of the atlas accompanied the fusion in 21 of the 25
      patients. The incidence of occipital or nuchal pains improved notably in most
      cases, and myelopathy was relieved in 12 of 18 (67%) cases, showing an
      improvement of more than one level based on Ranawat's criteria. No serious
      postoperative complications were seen, except for one case of a failed bone
      union. The cumulative survival in patients with myelopathy was 79.4% in the first
      5 years after operation and 27.5% at 10 years. Occipitocervical fusion using a
      rectangular rod accompanied by a decompressive laminectomy of the atlas can
      contribute to the relief of a neurologic deficit in an irreducible atlantoaxial
      dislocation in rheumatoid arthritis.

PMID- 9646760
TI  - Spontaneous union of a congenital pseudarthrosis of the tibia after Syme
      amputation.
AB  - A 4-year-old boy with congenital pseudarthrosis of the tibia had two unsuccessful
      operative attempts for union. After these procedures the patient had a 6-cm leg
      length discrepancy and an equinovalgus foot deformity. Because of these
      deformities he underwent Syme amputation at the ankle and was fitted with a total
      contact prosthesis. Eight months after the amputation, a solid union was seen
      across the pseudarthrosis site, although no attempt was made to achieve union
      with internal fixation or bone grafting. The authors think that vertical
      alignment of the limb in a total contact prosthesis, along with the compressive
      forces of weightbearing, allowed the pseudarthrosis site to heal in the patient.

PMID- 9646761
TI  - Intraoperative radiographic assessment of ankle fractures.
AB  - This retrospective study was performed to determine whether three or two
      radiographic views are necessary for intraoperative evaluation of low energy,
      rotational ankle fracture reduction and fixation. Four orthopaedic surgeons
      independently reviewed two sets of radiographs of 93 low energy, rotational ankle
      fractures treated by open reduction and internal fixation. The reviewers judged
      reduction and fixation, without measurement, as if they had been the operating
      surgeons. Set 1 consisted of mortise and lateral views and Set 2 consisted of
      anteroposterior, mortise, and lateral views. There was a 2-month interval between
      the review of Set 1 and Set 2. Intraobserver consistency for Sets 1 and 2 for
      reduction ranged from 92% to 98% and consistency for fixation ranged from 85% to
      94%. These results underwent statistical testing by calculation of the kappa
      value. With a 95% confidence interval, the kappa value for reduction ranged from
      0.376 to 0.701; the kappa value for fixation ranged from 0.598 to 0.781. The
      interobserver consistency for Sets 1 and 2 also was calculated. The authors
      conclude that fracture reduction and fixation can be assessed adequately with
      lateral and mortise views. The anteroposterior view can be eliminated from the
      standard radiographic protocol, potentially resulting in cost savings.

PMID- 9646762
TI  - Two open forearm fractures after airbag deployment during low speed accidents.
AB  - Automotive airbags effectively mitigate the impact of vehicular collision by
      absorbing and distributing a force that otherwise would be sustained by the
      occupants. To be effective, inflation must be instantaneous and sufficient to
      provide restraint to a moving body. Deployment of automotive airbags is a violent
      event that may cause injury to the occupants of the vehicle. This report
      describes two patients with severe, open radius and ulna fractures that were
      caused by airbag inflation during low velocity motor vehicle accidents. The
      degree of soft tissue injury and bone comminution in these patients was not fully
      appreciated until surgery. Orthopaedic surgeons should be aware of the explosive
      nature of airbag deployment and realize that the injury may be far greater than
      expected from a low energy motor vehicle accident.

PMID- 9646763
TI  - Effects of musculoskeletal neoplasms on patient self assessment of health status.
AB  - Eighty-five consecutive patients referred to the Musculoskeletal Tumor Service
      completed a standardized short form questionnaire to evaluate their health status
      and function. Each patient completing the Short Form-36 questionnaire had a
      diagnosis of musculoskeletal neoplasm, including benign soft tissue and bone
      tumors, malignant soft tissue and bone tumors, and metastatic tumors. The results
      of this preliminary study show that the authors' patient population experienced
      health status and functional deficits in each of the eight Short Form-36 assessed
      domains. Data show that the most severe deficits were experienced by patients who
      had diagnoses of bone tumors and malignant tumors. This study shows that the
      Short Form-36 is a practical and effective method for documenting perceived
      deficits in health status in patients with musculoskeletal tumors. These data
      allow the physician to understand the presenting condition from the patient's
      perspective. This is an important and often neglected aspect of the overall
      assessment of the health of patient on presentation. An understanding of these
      deficits is critical for effective planning of treatment and evaluation of
      treatment effectiveness.

PMID- 9646764
TI  - Biomechanical comparison of antegrade and retrograde nailing of humeral shaft
      fracture.
AB  - A pair-controlled study was conducted to compare biomechanical properties of
      antegrade and retrograde nailing of humeral fractures. First, six paired fresh
      anatomic specimen humeri were used to compare the properties of humeri fractured
      at the middle to distal diaphyses junction that were nailed from the retrograde
      approach with the Humeral Locked nail with those of contralateral intact humeri.
      An 18 additional pairs were divided into three equal groups by distal, proximal,
      or mid-diaphysis location of a standardized 5-mm bone defect to simulate unstable
      fractures. The retrograde and antegrade nailings were performed in each pair in a
      random manner. Nail and bone constructs were tested for bending stiffness by
      nondestructive three-point bending and for torsional stiffness by destructive
      torsional tests. Compared with intact humeri, fractured humeri fixed with nails
      had 28.6% posteroanterior and 31.4% mediolateral bending stiffness, 22.5%
      torsional stiffness, and 43.3% failure torque. For distal fractures, retrograde
      nailing showed significantly more initial stability and higher bending and
      torsional stiffness; for proximal fractures, antegrade nailing showed similar
      properties. For middle to distal diaphyses junction fractures, retrograde and
      antegrade nailing were indistinguishable. The defect created as an entry portal
      for retrograde nailing reduced the bone strength only 11.1%. These results
      suggest that retrograde nailing, which is less detrimental to shoulder function
      than is antegrade nailing, is an acceptable alternative treatment for humeral
      shaft fractures. In addition, nailing from the short to the long bone segments
      can improve mechanical properties of the fixation construct because of better
      nail and bone interface purchase.

PMID- 9646765
TI  - Analysis of muscle bioenergetic metabolism in rabbit leg lengthening.
AB  - The effect of lengthening on muscle metabolism was measured and correlated to the
      percent lengthening at early and late time points. Using the rabbit tibial
      lengthening model, the authors examined the effects of lengthening on the
      tibialis anterior muscle using phosphorus-31 magnetic resonance spectroscopy.
      Thirty-six rabbits were divided into five groups, four groups by percent
      lengthening (0%, 15%, 20%, and 25%), with each group divided into subgroups of
      early (end distraction) and late (12 weeks after end distraction), and the fifth
      group using the opposite untreated leg as control. Several parameters measuring
      metabolism of muscle using phosphorus-31 magnetic resonance spectroscopy analysis
      were compared. No changes occurred to 15% lengthening, but significant decreases
      were measured at 20% and 25% lengthening. After a 25% lengthening, the decreased
      metabolism persisted at 12 weeks after distraction, indicating the possibility of
      permanent damage. After 20% lengthening, the same parameters improved but never
      to normal levels. The authors conclude that lengthening to 15% is safe for
      muscle, but 20% to 25% lengthening may result in permanent metabolic damage. The
      current study also suggests that phosphorus-31 magnetic resonance spectroscopy
      may provide a viable clinical method for evaluating muscle damage during
      lengthening.

PMID- 9646766
TI  - The effect of translation of the C1-C2 on the spinal canal.
AB  - The stability of the atlantoaxial articulation depends fundamentally on the
      integrity of the odontoid process and the ligaments. Ligament stability mostly is
      maintained by two ligaments: the transverse ligament and the alar, apical
      ligaments. Failure of the transverse ligament can result in anterior translation
      of the atlas on the axis. The anteroposterior diameter of the ring of the atlas
      is approximately 3 cm. The spinal cord and the odontoid process are each
      approximately 1 cm in diameter, approximately 1/3 the diameter of the ring.
      According to Steel's rule of thirds, the remaining centimeter of free space
      allows for some degree of pathologic displacement. The current anatomic study
      showed that the space available for the spinal cord was limited. The sagittal
      diameter C1-C2 canal is 18.71 +/- 2.88 mm (excluding 10 mm thickness of the dens
      and 2.91 +/- 0.69 mm thickness of transverse ligament), with the spinal cord
      occupying 7.73 +/- 0.87 mm of the available space. Space available for spinal
      cord at the level of the atlas is 3.44 +/- 1.19 mm plus 1.01 +/- 0.20 mm space
      anterior to the cord (anterior epidural space) and 5.64 +/- 2.22 mm space
      posterior to the cord (posterior epidural space), which is approximately in
      agreement with the normal diameter by Steel's rule of thirds.

PMID- 9646767
TI  - Fracture healing and callus innervation after peripheral nerve resection in rats.
AB  - The effects of femoral and sciatic nerve resection on fracture healing and
      innervation of the fracture callus were studied using a stable fracture model. In
      34 rats the right tibia was subjected to a standardized closed fracture and
      stabilized with a modular intramedullary nail. In half of the animals, resection
      of 1 cm of the femoral and sciatic nerves was performed (nerve resection group),
      whereas the other animals had sham operations (sham group). To avoid unequal load
      bearing between the two groups, all fractured hindlimbs were immobilized in a
      plaster of Paris cast. The trial was terminated after 5 weeks of fracture
      healing. Callus size was scored radiographically, and bone mineralization was
      measured by 85-strontium incorporation. Seven rats from each group had
      immunohistochemical examination for neural regeneration and ingrowth. Antisera
      for protein gene product 9.5, neurofilaments, neural growth associated protein
      43/B-50, calcitonin gene related peptide, and substance P were used. The
      mechanical properties of the healing fractures were recorded in a three-point
      cantilever bending test. After 5 weeks, the normally innervated, fractured tibias
      had regained approximately 50% strength compared with the unfractured side, in
      comparison with only 20% in the animals that had nerve resection. Although the
      fracture calluses were mechanically weaker, they were significantly larger in the
      nerve resection group, indicating defects in tissue composition or organization
      rendered by the nerve injury. The mineralization rate, as measured by 85
      strontium incorporation, was the same in the two groups. However, the nerve
      resection did not provide complete denervation but changed the innervation
      pattern of the healing fracture, as the density of sensory nerve fibers
      immunostaining for substance P and neurofilaments was less in the group with
      femoral and sciatic nerve resection. The results suggest that intact innervation
      is essential for normal fracture healing because nerve injury induced a large,
      but mechanically insufficient, fracture callus.

PMID- 9646768
TI  - Possible mechanism of painful radiculopathy in lumbar disc herniation.
AB  - The pathophysiologic mechanisms of painful radiculopathy caused by a herniated
      intervertebral disc remain unknown. This study sought to determine whether the
      autologous intervertebral disc produces pain related behavior and whether
      phospholipase A2 and nitric oxide are involved in the pathophysiologic mechanism
      producing the behavior. A rat model, in which autologous intervertebral discs
      were implanted on the nerve root in the lumbar spine, was used to measure
      hyperalgesia, which is a pain related behavior in the rat. In this experimental
      model, autologous nucleus pulposus and anulus fibrosus transplanted to lumbar
      nerve roots produced mechanical and thermal hyperalgesia, respectively. Epidural
      injection of a selective inhibitor for phospholipase A2 resulted in the
      disappearance of hypersensitivity to noxious mechanical stimuli. Thermal
      hyperalgesia produced by application of the anulus fibrosus was abated and
      abolished by epidural injections of saline and one of the inhibitors for nitric
      oxide synthase, respectively. The authors suggest that chemical mediators such as
      phospholipase A2 and nitric oxide, induced by extruded or sequestrated
      intervertebral discs, are involved in the pathophysiologic mechanisms of painful
      radiculopathy in lumbar disc herniations. This study may be useful in attempting
      to develop new medical approaches for treatments of lumbar disc herniation.

PMID- 9646769
TI  - The Marshall R. Urist Young Investigator Award. Gene expression during autograft
      lumbar spine fusion and the effect of bone morphogenetic protein 2.
AB  - A prospective animal study of posterolateral lumbar spine arthrodesis was
      performed to determine the temporal and spatial pattern of gene expression and to
      determine the effect of recombinant human bone morphogenetic protein 2 on the
      gene expression pattern of a healing spine fusion mass. In Group 1, 20 adult New
      Zealand rabbits underwent L4-L5 posterolateral intertransverse process
      arthrodesis using autograft alone. Two rabbits were euthanized at each of the
      following points: 0, 2, and 4 days, and 1, 2, 3, 4, 5, 6, and 10 weeks after
      surgery. The same surgical technique was used for 16 rabbits in Group II, except
      that the autograft first was soaked in a solution of recombinant human bone
      morphogenetic protein 2 before implantation. Ribonucleic acid was extracted from
      different regions of the fusion mass at each point and analyzed for expression of
      bone and cartilage related genes using reverse transcription polymerase chain
      reaction. A reproducible temporal sequence and spatial pattern of gene expression
      was found in healing spine fusions. In the central portion of the fusion mass a
      temporal lag in gene expression was observed that parallels the lag in healing
      within the central zone previously observed in histologic studies. Treatment of
      bone graft with recombinant human bone morphogenetic protein 2 resulted in an
      increase in the early expression of bone morphogenetic protein 6 which was
      associated with expression of higher levels of Type I collagen, osteocalcin, and
      other bone related genes. These findings suggest that central nonunion may be
      associated with delayed expression of osteoblast related genes in the central
      region of the forming fusion mass. The growth factor, recombinant human bone
      morphogenetic protein 2, increased the level of bone related gene expression
      throughout the fusion mass, eliminated the delay in healing within the central
      zone, and may decrease the likelihood of a nonunion.

PMID- 9646770
TI  - Shoulder pain in a 26-year-old woman.

PMID- 9646771
TI  - Surgical technique of the midvastus arthrotomy.
AB  - For more than 25 years most surgeons have used a medial parapatellar surgical
      approach for total knee arthroplasty because this technique affords simplicity
      and excellent exposure to all compartments of the knee. This article describes
      how the midvastus muscle splitting approach achieves surgical exposure equivalent
      to that of the standard medial parapatellar approach, while preserving the
      integrity of the vastus medialis insertion into the medial border of the
      quadriceps tendon. This total knee arthroplasty approach divides the vastus
      medialis muscle in the direction of its fibers, as opposed to the traditional
      method of splitting the quadriceps tendon above the patella. The limited
      disruption of the extensor mechanism improves the rapid restoration of quadriceps
      muscle control. In addition, a more stable patellofemoral articulation is
      evidenced by a marked reduction in the need for lateral retinacular releases.

PMID- 9646772
TI  - [Determination of the onset of stroke. Satellite symposium: "Current Approaches
      to the Management of Acute Ischemic Stroke", part of the "6th European Stroke
      Conference". Amsterdam, 28 May 1997].

PMID- 9646773
TI  - Syndromes of thrombosis and hypercoagulability. Congenital and acquired causes of
      thrombosis.
AB  - Blood coagulation protein and platelet defects are now known to account for up to
      ninety percent of unexplained venous thrombosis and up to seventy percent of
      unexplained arterial thrombotic or ischemic events. This article summarizes the
      common and uncommon blood protein and platelet defects which should be suspected,
      and searched for, in patients with such events. Defining such defects will have
      major impact on secondary prevention and duration of antithrombotic therapy in
      the afflicted patient and impact on primary prevention for identified family
      members in those harboring hereditary defects.

PMID- 9646774
TI  - Diagnosis of deep venous thrombosis and pulmonary embolism.
AB  - Diagnostic evaluation in the patient with suspected deep vein thrombosis (DVT)
      and pulmonary embolism (PE) includes a clear correlation between clinical
      probability, test selection and test interpretation. Real-time B-mode ultrasound
      with color Doppler remains the imaging technique of choice in suspected DVT. The
      ventilation/perfusion (V/Q) lung scan is the preferred diagnostic modality in
      suspected PE. The D-dimer assay may be useful in excluding PA. New diagnostic
      techniques, including spiral computerized tomography may further modify the
      diagnostic algorithm.

PMID- 9646775
TI  - Prophylaxis of deep venous thrombosis and pulmonary embolism. Current
      recommendations.
AB  - Pulmonary embolism is responsible for approximately 150,000 to 200,000 deaths per
      year in the United States. Venous thromboembolism usually occurs as a
      complication in patients who are sick and hospitalized, but it may also affect
      ambulant and otherwise healthy individuals. Many patients who die from pulmonary
      embolism succumb suddenly or within 2 hours after the acute event (i.e., before
      therapy can be initiated or take effect). Therefore, prevention is the key to
      reducing death and morbidity from venous thromboembolism. Effective and safe
      prophylactic measures against venous thromboembolism are now available for most
      high-risk patients. This article highlights practical approaches to the
      prevention of venous thromboembolism.

PMID- 9646776
TI  - Treatment of deep venous thrombosis and pulmonary embolism. Current
      recommendations.
AB  - The therapy of deep venous thrombosis consists of several elements and depends on
      the localization, the age and the extent of the thrombus. This article discusses
      various types of initial therapy and long-term treatment of venous
      thromboembolism and also reviews future perspectives of pharmacological
      treatment. The initial treatment regimens comprise thrombolysis, thrombectomy,
      inferior vena cava filters and the anticoagulation with either unfractionated
      heparin or low molecular weight heparins. Various thrombin-inhibitors have been
      tested for initial treatment of thrombosis, however, further investigations of
      their efficacy, safety and cost-effectiveness will have to provide firm evidence
      on their superiority when compared to unfractionated or low molecular weight
      heparins.

PMID- 9646777
TI  - Thrombosis and cardiovascular disease.
AB  - The early stages of venous thrombosis originate at selective sites of reduced
      blood flow in the apices of venous valves. Stagnation of venous flow results in
      the formation of a platelet-fibrin thrombus, which serves as the nidus for
      thrombus propagation. Stasis alone, however, does not result in thrombosis
      necessarily. The presence of activated coagulation factors is essential. The
      major predisposing factors to venous thrombus are activation of blood coagulation
      and venous stasis. In contrast to venous thrombus formation, vascular
      abnormalities are the most important causative factor in arterial thrombosis.

PMID- 9646778
TI  - Thrombosis and cerebrovascular disease.
AB  - Strokes are heterogeneous not only with respect to their presentation, but more
      importantly in terms of the underlying pathology. There are now a number of
      choices available for the treatment of ischemic stroke, and the causative
      mechanisms responsible for each individual stroke must be considered in choosing
      an appropriate form of treatment. This article explores the underlying
      pathophysiological mechanisms responsible for the major categories of stroke and
      also examines the reasons why strokes worsen or evolve.

PMID- 9646779
TI  - Interventional use of plasminogen activators in central nervous system diseases.
AB  - Still an experimental approach, the direct intra-arterial infusion of plasminogen
      activators in the setting of acute thrombotic stroke has received impetus from
      successful clinical trials of intravenous infusion therapy. Direct therapy,
      employing catheter delivery, has successfully produced evidence of recanalization
      in carotid artery territory and vertebrobasilar artery territory thrombotic
      occlusions. One very recent prospective randomized study has demonstrated the
      success and limitations of this approach. Attention to safety concerns will be
      important to the future success of direct intra-arterial delivery of plasminogen
      activators in acute thrombotic stroke.

PMID- 9646780
TI  - Antithrombin agents as anticoagulants and antithrombotics. Implications in drug
      development.
AB  - Synthetic and recombinant thrombin inhibitors have undergone several clinical
      evaluations for thrombotic and cardiovascular indications. While the initial
      trials were focused in coronary indications, more recently, these agents are also
      developed for the prophylaxis and therapeutic management of thromboembolic
      disorders. Hirudin, PEG-hirudin and argatroban are in advanced clinical
      development. Recombinant hirudin has been approved in Europe as a substitute
      anticoagulant for the management of HIT patients. Several additional clinical
      trials are currently carried out to demonstrate the usefulness of these agents in
      thrombotic and cardiovascular indications. Despite these developments such issues
      as dosage optimization, laboratory monitoring, neutralization and drug
      interactions require additional studies for the optimal development of these
      drugs.

PMID- 9646781
TI  - Unfractionated and low-molecular-weight heparin. Comparisons and current
      recommendations.
AB  - Intravenous heparin followed by warfarin has been the classical anticoagulant
      therapy of acute venous thromboembolism for the past 30 years. In recent years a
      number of low-molecular-weight heparins have become available for clinical
      trials. These agents have a number of advantages over unfractionated heparin and
      are now being used internationally for the prevention and treatment of venous
      thromboembolism. Low-molecular-weight heparin will undoubtedly replace
      intravenous unfractionated heparin not only in the treatment of venous
      thromboembolism but in other conditions where heparin therapy is indicated.
      Whether or not the low-molecular-weight heparins can decrease or eliminate some
      of the complications of unfractionated heparin will depend on the outcome of
      future clinical trials.

PMID- 9646782
TI  - Current recommendations for warfarin therapy. Use and monitoring.
AB  - With the aging population, the use of warfarin will continue to increase. The
      introduction of new thromboplastins with International Sensitivity Indices (ISI)
      of 1.0 to 1.5 has improved the efficacy of monitoring warfarin therapy with the
      prothrombin time (PT). Increasingly, outpatient oral anticoagulant clinics and
      home testing are the sites for PT monitoring.

PMID- 9646783
TI  - International consensus recommendations. Summary statement and additional
      suggested guidelines. European Consensus Conference, November 1991. American
      College of Chest Physicians consensus statement of 1995. International Consensus
      Statement, 1997.
AB  - Since the NIH Consensus Conference in 1986, the developments in the field of
      prevention and treatment of venous thromboembolism were mainly characterized by a
      more specific and extended use of new prophylactic agents such as low-molecular
      weight heparins as well as the perception that out-patients may be at risk for
      thromboembolic complications, too. Therefore, in 1991 and 1995, consensus
      conferences were held in Europe and North America in order to analyze the risk
      constellation of various patient populations and to give recommendations for
      primary prophylaxis and treatment of thromboembolic complications. The most
      recent, the 1997 International Consensus Recommendations are also discussed.

PMID- 9646784
TI  - Heparin-induced thrombocytopenia, paradoxical thromboembolism, and other side
      effects of heparin therapy.
AB  - Although several new anticoagulant drugs are in development, heparin remains the
      drug of choice for most anticoagulation needs. The clinical effects of heparin
      are meritorious, but side effects do exist. Important untoward effects of heparin
      therapy including heparin-induced thrombocytopenia, heparin-associated
      osteoporosis, eosinophilia, skin reactions, allergic reactions other than
      thrombocytopenia and alopecia will be discussed in this article.

PMID- 9646785
TI  - Predictions for nuclear medicine in the next decade.

PMID- 9646786
TI  - The genesis of modern science: contributions of scientific societies and
      scientific journals.

PMID- 9646787
TI  - Imaging-guided gene therapy in the central nervous system.

PMID- 9646788
TI  - U.S. radiologists' workload in 1995-1996 and trends since 1991-1992.
AB  - PURPOSE: To measure U.S. radiologists' workload and the variation and trends in
      workload. MATERIALS AND METHODS: A stratified, random sample of 794 radiology
      practice groups were surveyed about hiring and workload in 1996; 78% responded.
      Responses were weighted to represent all U.S. radiologists. Types of procedures
      performed in Medicare patients in 1991 and 1995 were analyzed. RESULTS: In 1995
      1996, the average workload per full-time equivalent diagnostic radiologist was
      11,600 procedures +/- 200 (standard error) annually, an apparent (but not
      statistically significant) 5% increase from 4 years earlier. Average relative
      value units per Medicare procedure increased by 8%, due to the increasing role of
      magnetic resonance imaging, computed tomography, and interventional radiology.
      The annual average number of procedures varied substantially by group type (e.g.,
      13,200 procedures +/- 500 in groups of two to four radiologists vs 10,300 +/- 300
      in groups of 11 or more radiologists). Within any group type, radiologists at the
      75th percentile in terms of workload typically performed at least 50% more
      procedures than did radiologists at the 25th percentile. CONCLUSION: Given the
      large variability in the annual number of procedures within and across group
      types, averages should not be taken as norms. Contrary to concerns about a
      possible surplus of radiologists, the workload per radiologist has increased
      substantially in the past few years.

PMID- 9646789
TI  - Kawasaki disease: a review.

PMID- 9646790
TI  - US of the painful hip in childhood: diagnostic value of cartilage thickening and
      muscle atrophy in the detection of Perthes disease.
AB  - PURPOSE: To evaluate the combined use of several ultrasonographic (US) criteria
      in the detection of Perthes disease. MATERIALS AND METHODS: In a prospective
      study, 144 consecutive children with a painful hip underwent US. The thicknesses
      of the (a) anterior recess of the joint capsule, (b) cartilage of the femoral
      head, and (c) quadriceps muscle were assessed. Sixty-eight children with no
      symptoms, the control group, were also examined. RESULTS: The final diagnosis was
      transient synovitis (n = 58), Perthes disease (n = 21), slipped capital femoral
      epiphysis (SCFE; n = 5), or miscellaneous (n = 6). Fifty-four patients had no US
      or radiographic abnormalities, and symptoms disappeared during follow-up. The
      anterior recess in patients with transient synovitis was significantly wider than
      that in the other patients and control subjects (P < .001). Patients with Perthes
      disease showed significant cartilage thickening in the symptomatic hip compared
      with the other patients and control subjects (P < .001). Patients with Perthes
      disease and patients with SCFE showed significant atrophy of the ipsilateral
      quadriceps muscle compared with all other groups (P < .001). The combined use of
      these US criteria for the diagnosis of Perthes disease resulted in a positive
      predictive value of 95%, a negative predictive value of 95%, a sensitivity of
      71%, and a specificity of 99%. CONCLUSION: The combination of several US criteria
      increases the diagnostic value of US of the painful hip in patients with Perthes
      disease.

PMID- 9646791
TI  - Hip joint fluid: detection and distribution at MR imaging and US with cadaveric
      correlation.
AB  - PURPOSE: To define the magnetic resonance (MR) imaging appearance of a hip
      effusion. MATERIALS AND METHODS: Fifty-two asymptomatic hips in 26 volunteers
      aged 20-37 years and five fractured hips were imaged at 1.5 T with T2-weighting
      in three planes. Images were computer digitized and analyzed for hip fluid volume
      and visually assessed for the presence and width of fluid pockets (in
      millimeters) seen in the acetabular notch; recesses anterior, posterior, and
      lateral to the femoral head; and recesses anterior, posterior, and medial to the
      femoral neck. Cadaveric hips were also injected with graduated amounts of saline
      (1-20 mL), and sequential MR and ultrasound images were obtained. RESULTS:
      Computer analysis yielded an average fluid volume of 2.7 mL (range, 0.7-5.6 mL)
      in asymptomatic and 6.1 mL (range, 1.7-11.6 mL) in symptomatic hips. The mean
      difference between the right and left hips was 0.8 mL (range, 0.0-2.9 mL).
      Discrete fluid pockets, sometimes measuring greater than 5 mm in width, were
      commonly seen in asymptomatic hips. Distention of the capsule by at least 5 mm
      along the length of the femoral neck was almost always seen after injection of 5
      mL of saline and was consistently seen after injection of 10 mL of saline into
      cadaveric hips. CONCLUSION: Fluid adjacent to the entire length of the femoral
      neck, measuring at least 5 mm in width, is compatible with a joint effusion.

PMID- 9646792
TI  - Quantitative MR imaging evaluation of chondropathy in osteoarthritic knees.
AB  - PURPOSE: To determine the validity and the reliability of T1-weighted three
      dimensional gradient-echo magnetic resonance (MR) imaging for quantification of
      articular cartilage abnormalities of osteoarthritic knees. MATERIALS AND METHODS:
      Forty-three patients (mean age, 63 years) with knee osteoarthritis (American
      College of Rheumatology criteria) of the medial tibiofemoral compartment
      underwent a prospective, cross-sectional study. Knees were examined with a T1
      weighted three-dimensional gradient-echo sequence (1.4-mm contiguous sections),
      with use of a 0.2-T dedicated MR unit, before arthroscopic exploration. The
      tibiofemoral articular cartilage abnormalities were quantified blindly on both
      the MR and arthroscopic images with the French Society of Arthroscopy (SFA) score
      (0-100) and grading scheme (five grades). RESULTS: There was a statistically
      significant correlation between the SFA-arthroscopic score and the SFA-MR score
      (r = .83) and between the SFA-arthroscopic grade and the SFA-MR grade (weighted
      kappa = 0.84). The deepest cartilage lesions graded with arthroscopy and MR
      imaging showed correlation in the medial femoral condyle (weighted kappa = 0.83)
      and in the medial tibial plateau (weighted kappa = 0.84). The intraobserver
      reliability of the SFA-MR score was higher (r = .94) than the interobserver
      reliability (r = .80). CONCLUSION: Quantification of chondropathy with MR imaging
      is feasible and well correlated with anatomic cartilage breakdown.

PMID- 9646793
TI  - Evaluation of patellar cartilage in cadavers with a low-field-strength extremity
      only magnet: comparison of MR imaging sequences, with macroscopic findings as the
      standard.
AB  - PURPOSE: To assess a low-field-strength extremity-only magnet in the evaluation
      of patellar cartilage abnormalities. MATERIALS AND METHODS: Four regions in each
      of 10 patellae from cadavers were examined in the transaxial plane with a 0.2-T
      extremity-only magnet and the following sequences: T1-weighted spin echo, proton
      density- and T2-weighted turbo spin echo, short inversion time inversion
      recovery, and two- and three-dimensional gradient echo with and without
      magnetization transfer contrast subtraction. Lesions depicted with MR imaging and
      seen in anatomic sections of the patellae were classified according to a modified
      standardized arthroscopic grading system. MR imaging and pathologic correlation
      was then analyzed. RESULTS: On the basis of macroscopic findings, 14 of 40
      cartilage regions were found to be intact, grade 2A lesions were present in eight
      regions, grade 2B lesions in eight, and grade 3 lesions in 10. For the various MR
      imaging techniques, sensitivity was 25%-62% for grade 2A lesions, 50%-75% for
      grade 2B lesions, and 60%-90% for grade 3 lesions. Specificity was 81%-97% for
      grades 2A and 2B lesions, and 80%-97% for grade 3 lesions. Accuracy was 75%-82%
      for grade 2A lesions, 75%-92% for grade 2B lesions, and 80%-92% for grade 3
      lesions. CONCLUSION: High-grade cartilaginous lesions can be evaluated reliably
      with low-field-strength MR imaging by using a combination of imaging sequences.

PMID- 9646794
TI  - MR imaging of gene delivery to the central nervous system with an artificial
      vector.
AB  - PURPOSE: To determine whether gene delivery by means of a synthetic no viral DNA
      delivery system that is capable of gene transfer can be mapped with magnetic
      resonance (MR) imaging. MATERIALS AND METHODS: The DNA delivery system consisted
      of aminated (poly-L-lysine-conjugated) dextran chains anchored together with a
      central superparamagnetic core. Three different types of constructs were
      synthesized that differed in their amino content and, thus, DNA-loading capacity.
      The model plasmid consisted of complementary DNA encoding for humanized green
      fluorescent protein. Constructs were tested in cell culture and in vivo in a rat
      model. RESULTS: All three constructs were capable of transfecting human cells in
      culture with transfection efficiencies ranging from 0.3% to 4.1%, which is
      similar to that of diethylaminoethyl-dextran. MR imaging experiments showed that
      DNA constructs induced signal intensity changes that co-localized with phosphorus
      33-labeled plasmid distribution at autoradiography. After injection of the
      constructs into the corpus callosum of rats, weak green fluorescent protein
      expression of neuronal and glial cells could be detected at immunohistologic
      examination. CONCLUSION: Dextran-based nonviral DNA delivery systems are capable
      of transfecting cells and can be visualized with MR imaging.

PMID- 9646795
TI  - Excitotoxin-induced cerebral hyperemia in newborn piglets: regional cerebral
      blood flow mapping with contrast-enhanced power Doppler US.
AB  - PURPOSE: To create regional cerebral blood flow maps with contrast material
      enhanced power Doppler ultrasound (US). MATERIALS AND METHODS: In six
      anesthetized newborn piglets, cerebral hyperemia was induced after intrastriatal
      injection of 5 mumol of N-methyl-D-aspartic acid. Coronal power Doppler US was
      performed with a microbubble-based contrast agent, and cerebral blood flow was
      determined before and at 15, 30, and 60 minutes after injection. Images were
      digitized and analyzed for changes in mean pixel intensity. A bolus injection
      curve was constructed by plotting mean pixel intensity versus time, and the area
      under this normalized curve was compared with cerebral blood flow. RESULTS:
      Hemispheric cerebral blood flow increased from 40 mL/min/100 g +/- 1 (mean +/-
      standard error) to 90 +/- 12, 86 +/- 8, and 85 +/- 12 at 15, 30, and 60 minutes
      after injection, respectively (P < .0001 [analysis of variance]). Hemispheric
      mean pixel intensity at peak contrast also increased from 69 units +/- 5 to 120
      +/- 4, 112 +/- 6, and 98 +/- 13 at 15, 30, and 60 minutes after injection,
      respectively (P < .003). The area under the normalized curve correlated well with
      changes in hemispheric and striatal cerebral blood flow (r = .73, P = .0001; r =
      .62, P = .0001, respectively). CONCLUSION: In the newborn brain, regional blood
      flow maps can be created accurately with contrast-enhanced power Doppler US.

PMID- 9646796
TI  - Intraoperative assessment of microsurgery with three-dimensional optical
      coherence tomography.
AB  - PURPOSE: To evaluate three-dimensional optical coherence tomography (OCT) for use
      in the assessment of the microsurgical anastomoses of vessels and nerves.
      MATERIALS AND METHODS: OCT is an optical analogue of ultrasonography and is
      capable of imaging nontransparent biologic tissue by detecting backscattered
      infrared light. Cross-sectional in vitro images of rabbit and human vessels and
      nerves were obtained in as little as 125 msec at 10-micron resolution by using a
      solid-state laser as a light source. A surgical microscope was integrated with
      OCT to perform simultaneous imaging with en face visualization. Cross-sectional
      images were assembled to produce three-dimensional reconstructions of
      microsurgical specimens. RESULTS: Three-dimensional OCT reconstructions depicted
      the structure within an arterial anastomosis and helped identify sites of luminal
      obstruction. The longitudinal spatial orientation of individual nerve fascicles
      was tracked in three dimensions to identify changes in position. In vitro human
      arteries and nerves embedded in highly scattering tissue and not visible at
      microscopy were located and imaged with OCT at eight frames per second.
      CONCLUSION: The three-dimensional, micrometer-scale, diagnostic imaging
      capabilities of OCT permit rapid feedback for assessment of microsurgical
      procedures. OCT technology can be readily integrated with surgical microscopes
      and has potential for intraoperative monitoring to improve patient outcome.

PMID- 9646797
TI  - Myelolipoma: CT and pathologic features.
AB  - PURPOSE: To correlate clinical and pathologic patterns of myelolipoma with the
      computed tomographic (CT) appearance. MATERIALS AND METHODS: All cases of
      myelolipoma accessioned by the Armed Forces Institute of Pathology from 1981
      through 1997 were reviewed. CT images were scored for the location and size of
      each myelolipoma and the presence of calcification, hemorrhage, fat, and
      pseudocapsule. Pathologic findings for the pattern of fat and bone marrow
      elements were correlated with CT findings. RESULTS: In 74 patients, 86
      myelolipomas were found, of which 72 were in an adrenal gland (eight were
      bilateral), and 14 extra-adrenal masses were found in 10 patients. Four
      clinicopathologic patterns emerged: (a) isolated adrenal myelolipoma in 37
      patients (fat evident at CT, no other disorders present); (b) myelolipoma with
      hemorrhage in nine patients (imaging features similar to those of isolated
      adrenal myelolipomas but larger [mean diameter, 14.2 vs 9.9 cm; P = .01]; (c)
      extra-adrenal myelolipoma in 10 patients (imaging findings similar to those of
      adrenal myelolipomas, found most often in the retroperitoneum); and (d)
      myelolipomatous foci within other adrenal pathologic conditions in 18 patients
      (smaller, lower fat content, more heavily calcified). CONCLUSION: Myelolipomas
      are adrenal or extra-adrenal masses, with hemorrhage more common in larger
      lesions (diameter, > 10 cm). The CT appearance of myelolipomatous foci, which can
      be found within other pathologic adrenal conditions, is different from that of
      isolated adrenal myelolipomas.

PMID- 9646798
TI  - Ureterolithiasis: can clinical outcome be predicted with unenhanced helical CT?
AB  - PURPOSE: To evaluate the use of helical computed tomography (CT) without contrast
      material enhancement for prediction of a favorable outcome in ureterolithiasis.
      MATERIALS AND METHODS: CT studies were reviewed in 69 patients with a single
      ureteral stone not located at the ureteropelvic junction. CT findings (tissue rim
      sign, hydronephrosis, perinephric fat stranding, perinephric fluid collections,
      and thickening of renal fascia) were graded on a scale of 0-3. Stone diameter and
      renal parenchymal enlargement were also measured. RESULTS: Twenty-two patients
      had spontaneous passage, 12 did not respond to conservative treatment, and 35
      were lost to follow-up. When the latter 35 patients were excluded, perinephric
      fat stranding (P = .044) and perinephric fluid collections (P = .021) were graded
      significantly higher in patients with spontaneous stone passage. Mean stone
      diameter was significantly larger (P < .001) in patients in whom conservative
      treatment failed (mean, 7.8 mm) than in patients with spontaneous stone passage
      (mean, 2.9 mm). The presence of a tissue rim sign and the grade of
      hydronephrosis, renal fascial thickening, and renal parenchymal enlargement were
      not significantly different between the two groups. CONCLUSION: In addition to
      stone size, the degree of perinephric fat stranding and the presence of
      perinephric fluid collections are useful ancillary signs for help in predicting
      the likelihood of stone passage.

PMID- 9646799
TI  - Benign and malignant ovarian masses: selection of the most discriminating gray
      scale and Doppler sonographic features.
AB  - PURPOSE: To determine the gray-scale and Doppler sonographic features that best
      enable discrimination between malignant and benign ovarian masses and develop a
      scoring system for accurate diagnosis with these features. MATERIALS AND METHODS:
      Gray-scale and Doppler sonographic features of 211 adnexal masses were correlated
      with the final diagnosis; the most discriminating features for malignancy were
      selected with stepwise logistic regression. RESULTS: Twenty-eight masses were
      malignant and 183 benign. All masses with a markedly hyperechoic solid component
      or no solid component were benign. For masses with a nonhyperechoic solid
      component, additional features that allowed statistically significant
      discrimination of benignity from malignancy were, in decreasing order of
      importance, (a) location of flow at conventional color Doppler imaging, (b)
      amount of free intraperitoneal fluid, and (c) presence and thickness of
      septations. A scoring formula that made use of values based on the logistic
      regression equation had an area under the receiver operating characteristic curve
      of 0.98 +/- 0.01. The cutoff score with the highest accuracy had a sensitivity of
      93% and specificity of 93%. CONCLUSION: A solid component is the most
      statistically significant predictor of a malignant ovarian mass. A multiparameter
      scoring system that uses three gray-scale and one Doppler feature, developed by
      means of stepwise logistic regression, has high sensitivity and specificity for
      predicting malignancy.

PMID- 9646800
TI  - Deep pelvic abscesses: transperineal US-guided drainage.
AB  - PURPOSE: To examine the efficacy of transperineal sonographically guided drainage
      of deep pelvic abscesses. MATERIALS AND METHODS: Twelve drainage procedures were
      performed in 11 adults with symptoms of infection and cross-sectional images
      demonstrating a deep pelvic abscess. Eight patients had recently undergone
      abdominoperineal resection, seven of whom underwent preoperative radiation
      therapy. Two had chronic osteomyelitis with adjacent fluid collections, and one
      developed an infected hematoma after trauma. With ultrasound (US) guidance for
      initial access, catheters were placed for drainage in 11 procedures. One patient
      was treated with aspiration alone. Patients underwent clinical follow-up and
      subsequent imaging as necessary. RESULTS: Transperineal needle placement was
      successful in 12 of 12 patients (100%). In procedures that required catheter
      placement, 10 of 11 placements (91%) were achieved with the transperineal
      approach. One patient required fluoroscopic transvaginal catheter placement after
      opacification of the collection transperineally. Catheter drainage was maintained
      for 2-146 days (mean, 40 days; median, 21 days). Clinical success was achieved in
      nine of 10 patients (90%) by means of transperineal drainage. There were no
      complications, although premature catheter removal occurred in two patients.
      CONCLUSION: US-guided transperineal abscess drainage may be successfully
      performed in patients who cannot undergo conventional transabdominal,
      transvaginal, or transrectal catheter drainage.

PMID- 9646801
TI  - Lymphadenopathy: differentiation of benign from malignant disease--color Doppler
      US assessment of intranodal angioarchitecture.
AB  - PURPOSE: To differentiate reactive from malignant lymphadenopathy by using color
      Doppler ultrasonographic (US) findings of intranodal blood vessels. MATERIALS AND
      METHODS: Color Doppler US was performed in 117 lymph nodes in 100 consecutive
      patients before performance of surgical biopsy (47 nodes), neck dissection (62
      nodes), or high-speed core biopsy (eight nodes). The presence of malignant
      changes in intranodal angioarchitecture (focal perfusion defects, aberrant course
      of central vessels, displacement of intranodal vessels, subcapsular vessels) was
      evaluated in each node. Inter- and intraobserver variability were evaluated.
      RESULTS: Histopathologic examination demonstrated 48 reactive lymph nodes
      (longest diameter +/- standard deviation, 13.5 mm +/- 6.0), 56 nodal metastases
      (longest diameter, 19.2 mm +/- 8.8), 12 malignant lymphomas (longest diameter,
      23.2 mm +/- 10.5), and one node infiltrated by Langerhans cell histiocytosis. At
      color Doppler US, 103 (88%) nodes were classified correctly, with a specificity
      of 77% and a sensitivity of 96%. Reproducibility was 90%-96% (kappa = 0.79-0.91,
      P < .001). CONCLUSION: Color Doppler US is a reliable and reproducible method for
      help in the differentiation between reactive and malignant alterations of
      superficial lymph nodes by using findings of intranodal angioarchitecture.

PMID- 9646802
TI  - Head trauma: CT scan interpretation by radiology residents versus staff
      radiologists.
AB  - PURPOSE: To determine the rate and clinical outcome of discrepancies in
      interpretation by radiology residents and staff neuroradiologists of
      posttraumatic cranial computed tomographic (CT) scans. MATERIALS AND METHODS:
      Prospective evaluation was performed for 419 consecutive emergency posttraumatic
      cranial CT studies that had been interpreted by radiology residents on call over
      a 16-month period. Discrepancies between the interpretations made by residents
      and those made by staff radiologists were divided into two groups: failure to
      recognize an abnormality (false-negative finding) and interpretation of normal as
      abnormal (false-positive finding). Discrepancies were considered major if they
      could affect patient care in the emergency setting and minor if they could not.
      RESULTS: Major and minor discrepancies were 1.7% and 2.6%, respectively, among
      interpretations made by residents and those by staff radiologists. Major
      discrepancies were four subdural hematomas, one pneumocephalus, one hemorrhagic
      contusion, and one subarachnoid hemorrhage. Minor discrepancies included six
      skull and five facial fractures. The discrepancy rate was statistically
      significantly higher (12.2%) when CT findings were abnormal than when they were
      normal (1.5%). No change in treatment was attributed to the delay in diagnosis.
      CONCLUSION: A low discrepancy rate was found between interpretations made by
      radiology residents and those made by staff neuroradiologists of posttraumatic
      cranial CT scans. There were no adverse clinical outcomes.

PMID- 9646803
TI  - Small, patent cerebral aneurysms: atypical appearances at 1.5-T MR imaging.
AB  - PURPOSE: To determine the frequency and characteristics of small cerebral
      aneurysms with atypical appearances on magnetic resonance (MR) images. MATERIALS
      AND METHODS: MR imaging studies (n = 117) obtained at 1.5 T of small aneurysms (<
      1 cm diameter) were prospectively and retrospectively analyzed. Signal intensity
      characteristics and gadolinium-enhancement patterns in 84 aneurysms (62 patients)
      were evaluated. The patency of all aneurysms was confirmed at angiography or at
      the time of surgery. RESULTS: A characteristic signal void was seen on 62 (53%)
      of 117 studies. On the remaining 55 (47%) studies, aneurysms had atypical signal
      intensity that was isointense, heterogeneous, or hyperintense. Contrast-enhanced
      aneurysms were seen on 27 (53%) of 51 gadolinium-enhanced studies. CONCLUSION:
      Atypical MR imaging characteristics were seen in roughly half of cases. These
      atypical-appearing aneurysms may erroneously be considered to be thrombosed or be
      mistaken for other common lesions such as small tumors and be dismissed as
      nonvascular.

PMID- 9646804
TI  - Guillain-Barre syndrome: MR imaging findings of the spine in eight patients.
AB  - PURPOSE: To evaluate magnetic resonance (MR) imaging findings of the spine in
      patients with Guillain-Barre syndrome. MATERIALS AND METHODS: MR imaging findings
      in eight patients (three male, five female; age range, 2-47 years) with Guillain
      Barre syndrome were retrospectively reviewed. Guillain-Barre syndrome was
      diagnosed mainly on the basis of symptoms and also on the basis of supportive
      ancillary data, such as the results cerebrospinal fluid analysis and
      electrophysiologic evaluation. In addition, follow-up MR imaging was performed in
      three patients, who had slight clinical improvement. RESULTS: All patients had
      thickening of the intrathecal spinal nerve roots and cauda equina, with varying
      degrees of enhancement on gadolinium-enhanced axial T1-weighted images. Two
      enhancement patterns were noted. One was enhancement of both the anterior and
      posterior spinal nerve roots (n = 2); the other was enhancement of the anterior
      spinal nerve roots only (n = 6). Follow-up MR imaging in the three patients with
      slight improvement of symptoms revealed that the thickening and the degree of
      enhancement of the spinal nerve roots were diminished. CONCLUSION: Although the
      enhancement of the intrathecal spinal nerve roots is not specific to Guillain
      Barre syndrome and can be seen in neoplasia and other inflammatory processes, the
      enhancement of only the anterior spinal nerve roots is strongly suggestive of
      Guillain-Barre syndrome.

PMID- 9646805
TI  - The sugarcoating sign.

PMID- 9646806
TI  - Hypocalcemic stimulation and nonselective venous sampling for localizing
      parathyroid adenomas: work in progress.
AB  - PURPOSE: To evaluate whether the release of parathyroid hormone (PTH) from
      parathyroid tumors during selective parathyroid arteriography can help localize
      the tumors. MATERIALS AND METHODS: In 20 patients (six men, 14 women; age range,
      24-72 years) with parathyroid tumors undergoing parathyroid arteriography after
      failed surgery, serial measurements of PTH were obtained during selective
      arteriography with nonionic contrast material. PTH levels were measured in the
      superior vena cava (SVC) before and at varying times from 20 to 120 seconds after
      arteriography. RESULTS: A 1.4-fold increase in the PTH level of the
      postarteriographic SVC samples enabled correct prediction of the site of adenoma
      in 13 of the 20 patients (65%). Of nine patients with positive arteriograms,
      eight had positive results of postarteriographic sampling. Of 11 patients with
      negative arteriograms, five had positive results of postarteriographic sampling.
      CONCLUSION: Sampling the SVC for PTH gradients after selective parathyroid
      arteriography correctly indicated the site of the adenoma in 13 of 20 patients
      (65%).

PMID- 9646807
TI  - Dual-helical CT for detecting aortic atheromas as a source of stroke: comparison
      with transesophageal echocardiography.
AB  - PURPOSE: To investigate whether unenhanced dual-helical computed tomography (CT)
      is useful in the rapid, noninvasive detection of protruding aortic atheromas.
      MATERIALS AND METHODS: Thirty-two consecutive patients at least 50 years of age
      who had recent ischemic stroke, systemic emboli, or both, underwent
      transesophageal echocardiography (TEE) and unenhanced dual-helical CT with thin
      sections (section thickness, 3.2 mm; reconstruction increment, 1.5 mm). RESULTS:
      TEE demonstrated protruding aortic atheromas 15 patients (47%); dual-helical CT
      depicted protruding aortic atheromas in 13 of those 15 patients (87%). Of the 17
      patients without a protruding aortic atheroma at TEE, dual-helical CT helped
      confirm the absence in 14 (82%). Dual-helical CT yielded a sensitivity of 87%, a
      specificity of 82%, and an overall accuracy of 84%. Thirty-six protruding plaques
      were detected with TEE, of which 34 (94%) were correctly identified with dual
      helical CT. Of those 34 plaques, 27 (79%) contained variable amounts of calcium
      and seven (21%) showed hypoattenuation suggestive of soft plaques and thrombi. In
      six patients, dual-helical CT depicted a protruding aortic atheroma between the
      distal ascending aorta and the proximal arch; these plaques were not included in
      the comparative statistics and were analyzed separately. CONCLUSION: Unenhanced
      dual-helical CT with thin sections appears to be useful for the rapid,
      noninvasive detection of a protruding aortic atheroma, especially in areas not
      clearly visualized with TEE.

PMID- 9646808
TI  - Percutaneous drainage of fluid collections in the extremities.
AB  - PURPOSE: To analyze the results of percutaneous drainage of fluid collections in
      the extremities. MATERIALS AND METHODS: From 1990-1997, 28 patients aged 14-90
      years underwent percutaneous drainage of 33 fluid collections in the extremities;
      two patients underwent multiple drainages. Fluid collections were in the hip
      groin area (n = 16), thighs (n = 6), buttocks (n = 6), knees (n = 3), calf (n =
      1), and axilla (n = 1). Three intraarticular collections were included. The
      patients who had undergone prior procedures were eight who had undergone surgical
      drainage, 10 who had undergone needle aspiration, and one who had undergone
      surgical debridement. The two most common guidance methods of catheter placement
      were ultrasound localization and fluoroscopy. RESULTS: The average drainage
      duration was 18.2 days (range, 1-93 days). The estimated cavity sizes were 4-733
      cm3. Purulent fluid was drained in 13 patients. Staphylococcus aureus was the
      most commonly identified organism (n = 9). Nine patients had postoperative
      lymphoceles; five of these patients underwent sclerotherapy. Two (7%) patients
      had two complications, one of which was major. Failure occurred in four (16%) of
      25 patients; two needed repeat drainage for recurrence, and two needed subsequent
      surgery. Success could not be determined in three patients who were lost to
      follow-up. CONCLUSION: Percutaneous drainage of fluid collections in the
      extremities is an effective alternative to open-incision drainage in inpatients
      and outpatients.

PMID- 9646809
TI  - Coronary artery stenoses: assessment with contrast-enhanced electron-beam CT and
      axial reconstructions.
AB  - PURPOSE: To evaluate the usefulness of electron-beam computed tomography (CT) for
      identification of coronary artery stenoses. MATERIALS AND METHODS: Coronary
      angiography and contrast material-enhanced, electrocardiographically triggered
      electron-beam CT of the heart were performed in 23 patients. With axial CT images
      and axial maximum intensity projection reconstructions, the coronary arteries
      were assessed by two observers blinded to the results of angiography. RESULTS:
      Cardiac motion artifact (unsharpness) precluded evaluation of the right coronary
      artery (RCA) in six subjects and the left circumflex coronary artery (LCX) in one
      patient. With the vessels degraded by motion artifact eliminated from analysis,
      overall sensitivity of electron-beam CT for hemodynamically significant stenoses
      was 88%, and specificity was 79%. In the left anterior descending coronary artery
      (LAD), sensitivity was 93% and specificity was 63%; in the LCX, sensitivity was
      100% and specificity was 67%; and in the RCA, sensitivity was 67% and specificity
      was 77%. The presence of coronary artery calcification did not have an effect on
      sensitivity for stenoses, but it did decrease specificity. CONCLUSION: Electron
      beam CT angiography can depict hemodynamically significant stenoses in the LAD
      and LCX with a sensitivity of more than 90%. The presence of coronary artery
      calcification resulted in decreased specificity but no appreciable change in
      sensitivity.

PMID- 9646810
TI  - Brachytherapy for prophylaxis of restenosis after long-segment femoropopliteal
      angioplasty: pilot study.
AB  - PURPOSE: To evaluate in a pilot study the feasibility and efficacy of
      endovascular brachytherapy for prophylaxis of restenosis after femoropopliteal
      percutaneous transluminal angioplasty (PTA) without stent implantation in a group
      of patients with a high risk of restenosis. MATERIALS AND METHODS: Ten patients
      (six women, four men; mean age, 68 years) with long-segment (mean length, 16 cm;
      range, 9-22 cm) restenosis underwent PTA followed by endovascular irradiation
      with high-dose-rate afterloading of an iridium-192 rod. A dose of 12 Gy was
      targeted to the inner intimal layer of the vessel. Follow-up examinations until
      12 months after PTA included measurement of the ankle-brachial index, color
      duplex ultrasonography (US) with calculation of the peak velocity ratio, and
      intraarterial angiography when recurrence was suspected. RESULTS: Irradiation was
      technically feasible in all patients without complications. In six patients, the
      dilated and irradiated segment remained widely patent at color US, with
      corresponding excellent hemodynamic and clinical results after 12 months. In four
      patients, clinical and laboratory findings indicated recurrence and arteriography
      demonstrated restenosis with a diameter reduction of 60%, 70%, 80%, or 90%.
      CONCLUSION: Considering the negative selection of patients with a high risk of
      restenosis, the results of our pilot study are promising concerning the
      possibility of reduction of restenosis by means of endovascular brachytherapy
      after long-segment femoropopliteal PTA without stent implantation. The value of
      this approach should now be determined definitively in randomized trials.

PMID- 9646811
TI  - Bronchial carcinoid tumors: importance of prognostic factors that influence
      patterns of recurrence and overall survival.
AB  - PURPOSE: To analyze bronchial carcinoid characteristics that might influence
      patterns of disease recurrence and overall survival in patients with these
      tumors. MATERIALS AND METHODS: In a retrospective review, the actuarial rates of
      local relapse, regional relapse, and overall survival were determined in patients
      who had undergone resection of bronchial carcinoid tumors. The evaluable files
      for 87 patients (50 male, 37 female; age range, 15-82 years) who underwent
      resection of bronchial carcinoid cancer at the authors' institution between 1980
      and 1993 were reviewed for pathologic findings, extent of disease, and recurrence
      patterns after surgery. RESULTS: The actuarial 4-year overall survival, local
      control, and regional control rates in the entire cohort of patients were 89%,
      92%, and 94%, respectively. Univariate analyses revealed that an atypical
      histologic pattern was the only tumor-related factor that substantially affected
      local and regional control. Atypical histologic pattern and tumor size were among
      the multiple factors that independently affected overall survival. CONCLUSION:
      Atypical histologic findings in patients who had undergone complete resection of
      bronchial carcinoid tumors were associated with increased local-regional disease
      recurrence and decreased survival compared with recurrence and survival in
      patients with typical histologic findings.

PMID- 9646812
TI  - Hypertrophied bronchial artery at thin-section CT in patients with
      bronchiectasis: correlation with CT angiographic findings.
AB  - PURPOSE: To evaluate hypertrophied bronchial arteries on thin-section computed
      tomographic (CT) scans in patients with bronchiectasis by using CT angiographic
      correlation. MATERIALS AND METHODS: Spiral CT angiography was performed
      prospectively in 14 patients (eight men, six women; age range, 34-71 years) with
      bronchiectasis who were suspected of having bronchial arterial hypertrophy at
      thin-section CT (performed without contrast medium). The inclusion criteria were
      tubular (in six patients) or nodular (in 14 patients) areas of soft-tissue
      attenuation that had an appearance unlike that of lymph nodes at thin-section CT
      and that were within the mediastinum and around the central airway. These
      findings were subsequently correlated with the spiral CT angiographic findings.
      RESULTS: At comparative analysis of thin-section CT scans and CT angiograms,
      seven of the eight (88%) tubular lesions and 19 of the 36 (53%) nodular lesions
      in the mediastinal soft tissue were proved to be hypertrophied bronchial
      arteries. All of the six (100%) tubular and 19 of the 21 (90%) nodular lesions
      around the walls of the main (primary) and lobar bronchi were hypertrophied
      bronchial arteries. In eight (57%) patients, CT angiograms showed 11 intraluminal
      protrusions caused by hypertrophied bronchial arteries in the main bronchi, lobar
      bronchi, or both. CONCLUSION: Nodular and tubular structures in the mediastinum
      and around the central airway on thin-section CT scans in the patients with
      bronchiectasis are suggestive of hypertrophied bronchial arteries. Recognition of
      the hypertrophied bronchial artery can be critical for the bronchoscopist.

PMID- 9646813
TI  - Ventilator-associated pneumonia in patients with adult respiratory distress
      syndrome: CT evaluation.
AB  - PURPOSE: To determine the diagnostic accuracy of computed tomography (CT) for
      pneumonia in patients with adult respiratory distress syndrome (ARDS). MATERIALS
      AND METHODS: CT scans were obtained within 1 week of bronchoscopic sampling in 31
      patients receiving mechanical ventilation for ARDS for more than 48 hours. Of 11
      patients with pneumonia, five developed symptoms less than 11 days after the
      onset of ARDS (early ARDS). CT scans were rated for pneumonia independently by
      four radiologists who were unaware of the clinical diagnosis. Diagnostic accuracy
      was defined by means of the area under the receiver operating characteristic
      curve, or A2. RESULTS: Diagnostic accuracy for pneumonia was fair (A2 = 0.69 +/-
      0.04 [standard error]) owing to 70% true-negative ratings (vs 59% true-positive
      ratings). The generalizability coefficient was good (0.79). No single CT finding
      was significantly different for the presence of pneumonia. Nondependent opacities
      predominated in 10 (91%) of 11 patients with pneumonia and 12 (60%) of 20 without
      pneumonia. Nondependent opacities predominated in nine (56%) of 16 patients with
      early ARDS and 13 (87%) of 15 with late ARDS. CONCLUSION: CT has fair diagnostic
      accuracy for ventilator-associated pneumonia in patients with ARDS owing
      primarily to identification of patients without pneumonia. No single CT sign was
      significantly different for pneumonia, but dependent atelectasis was more common
      in patients with early ARDS without pneumonia.

PMID- 9646814
TI  - Pulmonary embolism: diagnosis with spiral CT and ventilation-perfusion scanning-
      correlation with pulmonary angiographic results or clinical outcome.
AB  - PURPOSE: To compare the accuracy of spiral computed tomography (CT) with that of
      ventilation-perfusion (V-P) scintigraphy in the diagnosis of pulmonary embolism
      (PE). MATERIALS AND METHODS: Fifty-four patients in whom indeterminate V-P scans
      or discordant clinical and scintigraphic results were obtained underwent both V-P
      scanning and contrast material-enhanced spiral CT. The reference standard was
      pulmonary angiographic results in 26 patients (group I) or clinical outcome in 28
      (group II). RESULTS: Six (25%) of 24 group I patients had proved PE. The
      prospective sensitivity and specificity for segmental or subsegmental PE were 67%
      and 100%, respectively, and the positive and negative predictive values were 100%
      and 90%, respectively. In two group II patients, V-P scans had high probability
      for acute embolism, but spiral CT scans showed only chronic PE; in one patients,
      the V-P scan had low probability and the CT scan was positive for acute PE. An
      alternative CT diagnosis was established in four (31%) of 13 patients in whom a
      normal or low-probability V-P scan was obtained. Clinical outcome was consistent
      with spiral CT results in all cases. CONCLUSION: Spiral CT has greater accuracy
      and specificity than V-P scanning in patients with an unresolved diagnosis and
      may be useful as the primary screening technique for PE.

PMID- 9646815
TI  - Unsuspected pulmonary embolism: prospective detection on routine helical CT
      scans.
AB  - PURPOSE: To determine the prevalence of unsuspected pulmonary embolism (PE) on
      routine thoracic helical computed tomographic (CT) scans and to quantify the
      improvement in PE detection by using a cine-paging mode on a workstation instead
      of hard-copy review. MATERIALS AND METHODS: Seven hundred eighty-five patients
      referred for routine contrast medium-enhanced thoracic CT within 9 months were
      prospectively recruited. Helical CT was performed. Studies were prospectively
      interpreted by four radiologists. Two radiologists performed routine, undirected,
      hard-copy consensus review for official interpretation; two of three thoracic
      radiologists independently performed a dedicated workstation-based search for PE.
      The presence of PE involving the main, lobar, or segmental pulmonary arteries was
      assigned a score of 1-5 (1 = definitely negative, 5 = definitely positive) by
      each independent reviewer. Patients with a score of 4 or 5 underwent lower
      extremity ultrasound, ventilation-perfusion scintigraphy, or both, followed by
      pulmonary CT angiography if the findings were still equivocal. RESULTS: Twelve
      (1.5%) of the 785 patients had unsuspected PE, with an inpatient prevalence of 5%
      (eight of 160) and an outpatient prevalence of 0.6% (four of 625). Of the 12
      patients with unsuspected PE, 10 (83%) had cancer. Of the 81 inpatients with
      cancer, seven (9%) had unsuspected PE. A dedicated workstation-based search
      resulted in detection of PE in three more patients (25%) than did hard-copy
      interpretation. CONCLUSION: The prevalence of unsuspected PE was highest among
      inpatients with cancer. A directed, workstation-based search can improve the PE
      detection rate over that with hard-copy review.

PMID- 9646816
TI  - Initially unresectable hilar cholangiocarcinoma: hepatic regeneration after
      transarterial embolization.
AB  - PURPOSE: To assess with volumetric computed tomography (CT) the pattern and
      extent of hepatic regeneration induced with transarterial embolization of
      initially unresectable hilar cholangiocarcinoma (Klatskin tumor). MATERIALS AND
      METHODS: In this prospective study, 13 patients (four men, nine women) with hilar
      cholangiocarcinoma, aged 43-74 years (mean +/- 1 standard deviation, 59.9 years
      +/- 9.6), underwent preoperative embolization of the right hepatic lobe.
      Embolization was performed transarterially by using four to 15 embolization
      coils. Volumetric measurements of the entire liver, left hepatic lobe, and spleen
      were performed with contrast material-enhanced and unenhanced helical CT before
      and after embolization in all patients. RESULTS: After right lobe embolization,
      volumetric helical CT measurements revealed a 2%-33% decrease (mean, 10%) in the
      volume of the affected right hepatic lobe, an 11%-68% increase (mean, 37%) in the
      volume of left hepatic lobe parenchyma, and variations in splenic volume of -5%
      to +28% (mean, +11%). Nine patients underwent extended hepatectomy 27-75 days
      (mean, 44 days) after embolization. No patient had severe complications due to
      embolization. CONCLUSION: In patients with an initially unresectable bilateral
      Klatskin tumor, right lobar arterial coil embolization results in enlargement of
      the left hepatic lobe (as verified with volumetric helical CT), thus allowing
      right hemihepatectomy.

PMID- 9646817
TI  - Hepatic infarction secondary to arterial insufficiency in native livers: CT
      findings in 10 patients.
AB  - PURPOSE: To describe the computed tomographic (CT) appearance of hepatic infarcts
      resulting from arterial insufficiency in native livers. MATERIALS AND METHODS:
      The authors retrospectively reviewed the clinical and imaging findings in 10
      patients (five men, five women; age range, 28-70 years) with 14 hepatic infarcts
      seen over 3 years. CT scans were analyzed for infarct appearance, vessel patency,
      and evolution of infarct pattern over time. RESULTS: Hepatic infarction resulted
      from hepatobiliary surgery (n = 6), radiologic intervention (n = 3), and celiac
      occlusion secondary to antiphospholipid syndrome (n = 1). All 14 infarcts were of
      low attenuation, peripheral, and wedge-shaped. Occluded arterial vessels were
      identified in eight patients. Follow-up CT revealed infarct diminution with
      parenchymal atrophy and scarring (n = 5), progressive liquefaction (n = 2), or
      both parenchymal atrophy and progressive liquefaction (n = 1). CONCLUSION: Sudden
      interruption of hepatic arterial flow may cause acute native liver infarction.
      Patients at risk include those with underlying vascular disease who undergo
      complicated surgical procedures and those undergoing peripheral arterial
      embolization.

PMID- 9646818
TI  - Mucin-producing pancreatic tumors: comparison of MR cholangiopancreatography with
      endoscopic retrograde cholangiopancreatography.
AB  - PURPOSE: To compare magnetic resonance cholangiopancreatography (MRCP) with
      endoscopic retrograde cholangiopancreatography (ERCP) in the detection of mucin
      producing pancreatic tumors. MATERIALS AND METHODS: The authors retrospectively
      reviewed MRCP and ERCP images obtained in 28 patients with mucin-producing
      pancreatic tumors. Detectability of the pancreatic duct and its branches,
      intraductal cystic lesions, and intracystic nodules or septa was assessed.
      RESULTS: MRCP depicted cystic dilated ductal branches significantly better than
      did ERCP (P < .001). The difference in the number of nodules or septa detected
      with MRCP compared with ERCP was not significant. MRCP, however, simultaneously
      showed not only the main pancreatic duct but also the cystic lesions; this was
      not always possible with ERCP. CONCLUSION: MRCP appears to be more effective and
      less invasive than ERCP to evaluate changes in the size and extent of tumors and
      to determine if new lesions appear, as well as to follow up mucin-producing
      pancreatic tumors.

PMID- 9646819
TI  - Gastric mucosa-associated lymphoid tissue lymphoma: radiographic findings in six
      patients.
AB  - PURPOSE: To determine the radiographic findings of low-grade gastric mucosa
      associated lymphoid tissue (MALT) lymphoma on double-contrast upper
      gastrointestinal studies. MATERIALS AND METHODS: Pathology records, double
      contrast upper gastrointestinal studies, and medical records of six patients with
      gastric MALT lymphoma were retrospectively reviewed. RESULTS: The most common
      clinical findings at presentation included epigastric pain (n = 6), dyspepsia (n
      = 4), and nausea and vomiting (n = 4). Double-contrast studies revealed rounded,
      often confluent nodules of varying size in four patients with low-grade MALT
      lymphoma. Nodularity was located in the gastric antrum (n = 2), body (n = 1), or
      body and fundus (n = 1). A fifth patient had a malignant-appearing 1-cm-diameter
      antral ulcer, and a sixth had a 10-cm-diameter polypoid, ulcerated mass in the
      gastric fundus. The latter patient was found to have high-grade MALT lymphoma
      with low-grade MALT lymphoma abutting the tumor. Five patients had associated
      Helicobacter pylori gastritis. Five patients had stage I disease, and one had
      stage IIB disease. At endoscopic follow-up (n = 4), marked regression of tumor
      occurred after treatment with antibiotics, chemotherapy, and/or radiation
      therapy. CONCLUSION: When low-grade MALT lymphoma is suspected on the basis of
      barium study results, endoscopic biopsy specimens should be obtained for a
      definitive diagnosis so these patients can be treated before the development of
      high-grade gastric lymphoma.

PMID- 9646820
TI  - Screening behavior of women after a false-positive mammogram.
AB  - PURPOSE: To determine the effect of a false-positive mammogram that leads to open
      surgical biopsy on subsequent screening mammography behavior in women. MATERIALS
      AND METHODS: This study was performed with a retrospective cohort design, and
      data were collected by means of telephone interview. All participants were women
      aged at least 50 years, with no history of breast cancer. Study patients (n = 43)
      were women who had an abnormal mammogram followed within 6 months by benign
      excisional breast biopsy. Control subjects (n = 136) were randomly selected: They
      included women with a normal mammogram who had not undergone biopsy, as well as
      women with an abnormal mammogram and the recommendation to undergo 6-month follow
      up mammography. RESULTS: Two differences between the study and control groups
      were statistically significant. Study patients were more likely than control
      patients to believe they had increased susceptibility to breast cancer (P =
      .039). Study patients were also more likely than control subjects to intend to
      undergo screening mammography annually in the future (P = .036). CONCLUSION: A
      false-positive mammogram that leads to open surgical biopsy does not inhibit most
      women from undergoing subsequent screening mammography. In fact, such an
      experience may increase their intentions to undergo regular screening.

PMID- 9646821
TI  - Calcification retrieval at stereotactic, 11-gauge, directional, vacuum-assisted
      breast biopsy.
AB  - PURPOSE: To determine the frequencies of calcification retrieval and histologic
      underestimates at stereotactic, 11-gauge, directional, vacuum-assisted breast
      biopsy. MATERIALS AND METHODS: Retrospective review of records revealed 112
      calcific lesions in 80 women (aged 31-85 years) who underwent stereotactic, 11
      gauge, directional, vacuum-assisted biopsy; a mean of 14 specimens per lesion
      were obtained. Calcification retrieval was defined as identification of
      calcifications on radiographs of specimens. Atypical ductal hyperplasia (ADH)
      underestimates were lesions that yielded ADH at stereotactic biopsy and carcinoma
      at surgery. Ductal carcinoma in situ (DCIS) underestimates were lesions that
      yielded DCIS at stereotactic biopsy and infiltrating carcinoma at surgery.
      Mammograms, stereotactic images, radiographs of specimens, and histologic
      findings were reviewed. RESULTS: Stereotactic, 11-gauge, directional, vacuum
      assisted biopsy removed all calcifications in 51 (46%) lesions, some
      calcifications in 55 (49%) lesions, and no calcifications in six (5%) lesions.
      Failure to retrieve calcifications was significantly more likely in lesions 5 mm
      or smaller (12% [five of 43] vs 1% [one of 69], P = .03), in calcifications with
      amorphous morphology (21% [three of 14] vs 3% [three of 98], P < .03), or if the
      probe was fired outside the breast (12% [five of 40] vs 1% [one of 72], P = .02).
      Surgery revealed DCIS in one (10%) of 10 lesions that yielded ADH at stereotactic
      biopsy. Surgery revealed infiltrating carcinoma in one (5%) of 21 lesions that
      yielded DCIS at stereotactic biopsy. No underestimation occurred when all
      calcifications were removed. CONCLUSION: Stereotactic, 11-gauge, directional,
      vacuum-assisted biopsy resulted in successful calcification retrieval in 106
      (95%) of 112 cases. Histologic underestimation was infrequent.

PMID- 9646822
TI  - Vogele-Bale-Hohner mouthpiece: registration device for frameless stereotactic
      surgery.

PMID- 9646823
TI  - Pneumothorax after fine-needle aspiration biopsy.

PMID- 9646824
TI  - Liver hemangioma: US-guided core-needle biopsy.

PMID- 9646825
TI  - Specimen weights obtained with 14- and 11-gauge breast biopsy probes.

PMID- 9646826
TI  - Hard- versus soft-copy readings of computed radiographs.

PMID- 9646827
TI  - Human chorionic gonadotropin levels in the evaluation of ectopic pregnancy.

PMID- 9646828
TI  - Silicone gel and animal models of autoimmune disease.

PMID- 9646829
TI  - Apoptosis and thyroiditis.
AB  - The origin of the various forms of autoimmune thyroiditis remains unclear. Most
      investigations into the pathogenesis of these disorders have focused on immune
      abnormalities that might lead to an autoimmune response. However, no unique
      immune response to thyroid autoantigens has been identified that either is
      limited to patients with thyroiditis or is absolutely correlated with clinical
      disease expression. CD8 T-cell-mediated cytotoxicity is thought to be a major
      cause of thyroid follicular cell damage in thyroiditis. This damage is produced
      in part through the induction of apoptosis in thyroid cells. Recent studies have
      demonstrated that programmed cell death is regulated in thyroid cells and that a
      major pathway for immune-mediated apoptosis, the Fas pathway, is blocked by
      labile inhibitors in a manner that could prevent cytotoxicity. This review also
      examines several other types of regulation of apoptotic pathways in thyrocytes.
      We hypothesize that the regulation of programmed cell death pathways in the
      thyroid may alter the expression of autoimmune thyroid diseases by modifying the
      susceptibility of thyroid cells to immune-mediated apoptosis.

PMID- 9646830
TI  - Lymphotactin.

PMID- 9646831
TI  - Smokeless tobacco extracts activate complement in vitro: a potential pathogenic
      mechanism for initiating inflammation of the oral mucosa.
AB  - The use of smokeless tobacco has been linked to an increased incidence of
      inflammation of the buccal and gingival mucosa. However, the mechanisms by which
      smokeless tobacco initiates inflammation are not well understood. The complement
      cascade is a ubiquitous source of proinflammatory molecules and can be activated
      rapidly by a wide variety of agents. Therefore, the effect of smokeless tobacco
      on complement was investigated as a potential pathogenic mechanism for triggering
      inflammation of the oral mucosa. Aqueous extracts of loose leaf chewing tobacco
      (1S1), dry snuff (1S2), and moist snuff (1S3), added to normal human serum,
      depleted complement hemolytic activity in a dose-dependent manner. Experiments
      utilizing sera deficient in one specific complement component indicated that the
      smokeless tobacco-induced depletion of hemolytic activity was due largely to
      consumption of C3. Furthermore, assays designed to test the activity of the
      alternative pathway of complement clearly showed that all three extracts depleted
      the hemolytic activity of this pathway. Finally, all three smokeless tobacco
      extracts activated the alternative pathway since significantly elevated levels of
      the cleavage fragments iC3b and Bb were detected in extract-treated serum. High
      quantities of the classical pathway cleavage fragment C4d also were detected in
      serum treated with moist snuff (1S3). The results clearly demonstrate that
      smokeless tobacco extracts activate the alternative pathway and also suggest some
      measure of classical pathway activation. Activation of complement by smokeless
      tobacco may be a mechanism for initiating inflammation of the oral mucosa.

PMID- 9646832
TI  - Differential expression of bcl-2 and susceptibility to programmed cell death in
      lymphocytes of HIV-1-infected individuals.
AB  - The bcl-2 protooncogene encodes an inner mitochondrial membrane protein that
      blocks programmed cell death. There is now increasing evidence that regulation of
      bcl-2 expression is a determinant of life or death in normal lymphocytes. In this
      study, we examined bcl-2 expression in lymphocytes from human immunodeficiency
      virus type 1 (HIV-1)-infected and healthy subjects by flow cytometry. bcl-2
      expression was detected in more than 97% of peripheral blood lymphocytes in both
      healthy and HIV-infected individuals. It was consistently observed that CD4+
      lymphocytes from HIV-1-infected individuals with less than 200 CD4+
      cells/microliter expressed significantly less bcl-2 than healthy controls. In
      contrast, bcl-2 expression in CD8+ lymphocytes of these patients was
      significantly enhanced. No significant alteration of bcl-2 expression was found
      when lymphocytes of healthy individuals were polyclonally activated in the
      presence of various regulatory cytokines. Cells undergoing apoptosis showed
      significantly lower bcl-2 expression than viable cells. Staining of apoptotic
      cells revealed that lymphocytes from HIV-1-infected subjects were characterized
      by an increased susceptibility to programmed cell death which was not restricted
      to a particular lymphocyte subset. Despite significantly different bcl-2
      expression in CD4+ and CD8+ lymphocytes of HIV-1-infected individuals with less
      than 200 CD4+ cells/microliter, no difference could be observed concerning their
      susceptibility to undergo apoptosis. Therefore, we conclude that sensitivity or
      resistance to in vitro induction of apoptosis does not directly correlate with
      bcl-2 expression.

PMID- 9646833
TI  - Cell death and oxidative damage in inflammatory myopathies.
AB  - There is evidence that muscle fibers in denervating disorders and muscular
      dystrophies undergo apoptosis. In 21 patients with autoimmune inflammatory
      myopathies, we found no features of muscle fiber apoptosis such as DNA
      fragmentation or expression of apoptosis-related proteins. However, muscle fibers
      in myositis displayed distinct up-regulation of inducible and neuronal nitric
      oxide synthase (NOS). While inducible NOS was distinctly up-regulated on the
      sarcolemma of all kinds of muscle fibers neuronal NOS displayed increased
      expression in the sarcoplasm of damaged as well as atrophic muscle fibers. There
      were no disease-specific patterns in the different myositis subtypes. Enhanced
      expression of NOS with production of nitric oxide may contribute to oxidative
      stress mediating muscle fiber damage and muscle fiber necrosis representing the
      predominant cell death mechanism in myositis. Nevertheless, inflammatory cells
      displayed numerous DNA-fragmentation-positive nuclei and expression of apoptosis
      related proteins indicating that apoptosis plays a role in the regulation of the
      inflammatory cellular response.

PMID- 9646834
TI  - Silicone gel enhances the development of autoimmune disease in New Zealand black
      mice but fails to induce it in BALB/cAnPt mice.
AB  - Anecdotal evidence links silicone gel breast implants with the development of
      autoimmune connective tissue disease in women. To investigate whether silicone
      gel is capable of directly inducing and/or enhancing the development of
      autoimmune disease, female BALB/cAnPt (BALB/c) and New Zealand Black (NZB) mice
      were injected subcutaneously with silicone gel, pristane, a nonmetabolizable
      substance that can cause plasmacytomas in BALB/c and NZB mice, or saline and
      monitored for the development of glomerulonephritis and autoantibody production.
      NZB, but not BALB/c, mice spontaneously develop autoantibodies and an autoimmune
      hemolytic anemia by 12 months of age. Over a period of 10 months, biweekly
      screening for proteinuria revealed increases in urinary protein in NZB mice that
      received multiple injections of either silicone gel or pristane. In contrast,
      urinary protein was unaffected in identically treated BALB/c mice. Although,
      silicone gel had no effect on serum titers of antierythrocyte antibodies in NZB
      mice, the hematocrits were significantly decreased. Moreover, silicone gel both
      increased the concentration of IgM anti-type I collagen antibodies and skewed the
      immunofluorescent staining pattern of serum autoantibodies on HEp-2 cells. In
      contrast, silicone gel failed to induce the production of anti-erythrocyte or
      antinuclear antibodies in BALB/c mice and induced only slight increases in IgG
      anti-type I collagen antibodies. These results suggest that silicone gel can
      exacerbate the development of autoimmune disease in autoimmune NZB mice, but
      fails to induce disease in normal BALB/c mice. This is consistent with several
      epidemiological studies failing to demonstrate an increase in the incidence of
      autoimmune disease in women with breast implants. However, because silicone gel
      was able to exacerbate autoimmune disease in NZB mice, it may play a similar role
      in the development of autoimmune disease in a small percentage of women who are
      genetically susceptible to such diseases.

PMID- 9646835
TI  - Effect of aging on experimental autoimmune prostatitis: differential kinetics of
      development.
AB  - We have studied the influence of aging on the kinetics of autoimmune response in
      Experimental Autoimmune Prostatis (EAP). EAP was induced in 3- and 12-month-old
      Wistar rats by i.d. immunization with a saline extract of rat male sex accessory
      glands (RAG), chemically modified, and emulsioned in CFA. After immunization, 12
      month-old rats developed a faster and stronger specific DTH response against RAG
      and mononuclear infiltration in the prostate. The levels of total IgM and IgG
      against RAG were lower in 12-month-old rats than in 3-month-old rats, with a
      prevalence of IgG2a, IgG2b, and IgG2c subclasses in both ages. Immunization
      stimulated slightly the appearance of specific IgG1 to RAG only in 3-month-old
      rats but in 12-month-old rats there was no specific IgG1 to RAG. On the other
      hand, normal 12-month-old rats showed higher levels of some natural antibodies
      and their thymocytes and peripheral lymphocytes had a diminished proliferative
      capacity compared to 3-month-old rats. These data demonstrated that 12-month-old
      rats show parameters of an aged immune system and present an exacerbated
      autoimmune prostatitis compared with 3-month-old rats.

PMID- 9646836
TI  - The effect of B cell deficiency on the immune response to acetylcholine receptor
      and the development of experimental autoimmune myasthenia gravis.
AB  - To study the involvement of B cells in the immune response to acetylcholine
      receptor (AChR), B-cell-deficient (mu mutant) and control wild-type C57BL/6 mice
      were immunized with AChR and assessed for clinical and immunopathological
      manifestations of experimental autoimmune myasthenia gravis (EAMG). The mu mutant
      mice failed to generate anti-AChR antibodies and were completely resistant to the
      induction of EAMG. However, mu mutant mice developed clinical EAMG when
      antibodies to the AChR main immunogenic region were passively transferred.
      Further, the in vivo expansion of lymph node cells after AChR immunization was
      greatly impaired in mu mutant mice. The mu mutant mice gave an effective in vitro
      T cell immune response to the immunodominant pathogenic AChR alpha chain peptide
      146-162 (alpha 146-162) and to the whole AChR protein when tested on day 90 after
      immunization with AChR, whereas the response to both AChR and its alpha 146-162
      peptide was reduced when tested on day 7 after immunization. The in vitro
      production of IFN-gamma and IL-2 by AChR-specific and alpha 146-162 peptide
      specific lymphocytes was lower in mu mutant mice. The AChR immune mu mutant T
      cells proliferated and produced IFN-gamma when AChR or alpha 146-162 peptide was
      presented by wild-type irradiated AChR-primed antigen-presenting cells (APCs).
      This indicates that B cells are important in the processing and presentation of
      AChR dominant peptide in vitro during the initial immune response to AChR.
      However, APCs of non-B-cell lineage are sufficient to process AChR and prime the
      T cells to AChR dominant T cell epitope peptides.

PMID- 9646837
TI  - Eye muscle antibodies in patients with ocular myasthenia gravis: possible
      mechanism for eye muscle inflammation in acetylcholine-receptor antibody-negative
      patients.
AB  - Myasthenia gravis is an organ-specific autoimmune disorder generally thought to
      be caused by an antibody-mediated attack against the skeletal muscle nicotinic
      acetylcholine (Ach) receptor (AchR) at the neuromuscular junction. Extraocular
      muscle weakness and double vision are present in about 90% of patients with
      myasthenia gravis and are the predominant complaints in about 20% of patients,
      when the condition is called ocular myasthenia gravis (OMG). While serum
      antibodies against the AchR are detected in most patients with generalized
      myasthenia gravis (GMG), they are not found in about one-third of patients with
      the ocular variety, and epidemiological, clinical, and serological studies
      suggest that OMG and GMG are two separate diseases. Both forms of myasthenia
      gravis are sometimes associated with thyroid autoimmunity or thyroid-associated
      ophthalmopathy (TAO). We have therefore tested the sera of patients with GMG and
      OMG by Western blotting for antibodies against porcine eye muscle membrane
      proteins in general, and by enzyme-linked immunosorbent assays (ELISA)
      specifically for reaction with two skeletal muscle antigens which are prominent
      marker antigens for TAO, namely, the calcium-binding protein calsequestrin and
      the so-called "64-kDa protein." The 64-kDa protein has recently been identified
      as the flavoprotein subunit of mitochondrial succinate dehydrogenase. Patients
      with ophthalmopathy and myasthenia were excluded. Nine of the patients had
      associated Graves' hyperthyroidism without evident ophthalmopathy and one had
      Hashimoto's thyroiditis. Antibodies against porcine eye muscle membrane antigens
      of M(r) 15-110 kDa were detected in patients with GMG or OMG, one or more
      antibodies being detected in 100% of patients with GMG and in 88% of those with
      OMG. The most frequently found antibodies were those targeting eye muscle
      membrane proteins of 15, 67, and 110 kDa. Antibodies reactive with purified
      calsequestrin (63 kDa) were detected in 21% of patients with OMG but in no
      patient with GMG. Antibodies recognizing purified succinate dehydrogenase (67
      kDa) were found in 42% of patients with OMG, in 100% (5 of 5) of patients with
      GMG, and in 48% of all patients with myasthenia gravis not associated with
      Graves' hyperthyroidism. There was no close correlation between any eye muscle
      reactive antibody and antibodies against the AchR in either group of myasthenic
      patients. The findings support the notion that immunoreactivity against skeletal
      muscle proteins other than the AchR may play a role in the development of the
      muscle weakness in AchR antibody-negative patients with OMG and GMG, although it
      is unlikely that any of the antibodies demonstrated in this study are directly
      implicated. Similarly, while the demonstration of antibodies reactive with eye
      muscle antigens associated with TAO in patients with OMG raises the possibility
      that the link between the ocular lesions of myasthenia gravis and Graves' disease
      may be autoimmunity against a common antigen(s), it is more likely that both
      disorders are mediated by cytotoxic T cells recognizing another cell membrane
      antigen, such as the novel thyroid and eye muscle shared protein G2s, and that
      serum antibodies reactive with succinate dehydrogenase Fp subunit and
      calsequestrin are markers of an immune-mediated eye muscle reaction.

PMID- 9646838
TI  - Induction of oral tolerance in splenocyte-reconstituted SCID mice.
AB  - The participation of each lymphocyte compartment in the induction of oral
      tolerance for antibody response was investigated by means of a new cell-transfer
      experimental system, using severe combined immunodeficiency (SCID) mice. Various
      lymphocyte compartments from BALB/c mice were transferred into SCID mice and
      these mice were evaluated for oral tolerance induction. First, whole splenocytes
      from BALB/c mice were transferred into SCID mice and these mice were orally
      administered bovine alpha s1-casein. The specific antibody response in these mice
      after subsequent immunization with antigen was greatly reduced compared to
      controls which were not fed the antigen, and it was demonstrated that oral
      tolerance was induced in SCID mice bearing donor splenocytes. Oral tolerance was
      induced in SCID mice that were reconstituted with only T cells, revealing that B
      cells were not required for the induction of oral tolerance. Further, oral
      tolerance was induced in SCID mice reconstituted with CD8-depleted splenocytes
      but not in mice reconstituted with only CD8+ T cells. These results demonstrate
      that oral tolerance could be induced in SCID mice bearing normal splenocytes and
      that interaction of CD4+ T cells with antigen-presenting cells other than B cells
      are responsible for the induction of oral tolerance. Our experimental system may
      be useful for investigations with human lymphocytes.

PMID- 9646839
TI  - The association between anti-ribosomal P antibodies and active nephritis in
      systemic lupus erythematosus.
AB  - Autoantibodies to anti-ribosomal P protein have been recognized in patients with
      systemic lupus erythematosus (SLE) in widely variable proportions of unselected
      patients. Presence of anti-ribosomal P antibodies was retrospectively studied in
      69 patients with SLE during disease exacerbations and remissions or during
      continuously active disease. Anti-ribosomal P antibodies were positive in 21/69
      patients during active disease, with an overall prevalence of 30.4%. Prevalence
      in patients with active nephritis was 75.0% (15/20), P value by Fisher's exact
      test of 8.39 x 10(-7). In 12/13 patients (92.3%), anti-P disappeared during
      periods of disease remission, P = 0.0002. In 17/21 patients (81.0%) with anti
      ribosomal P antibodies, anti-dsDNA antibodies were also positive. In 47 patients
      without anti-P, 23/47 (48.9%) were also positive for anti-dsDNA. In 9/12 patients
      (75.0%) titers of anti-dsDNA antibodies correlated with anti-P during disease
      exacerbations and remissions, P = 0.004. The higher prevalence of anti-P in
      patients with lupus nephritis with disappearance during disease remissions
      supports the hypothesis of an immunopathogenetic role of these antibodies in
      lupus nephritis. There was also a strong association between anti-dsDNA and anti
      P antibodies.

PMID- 9646840
TI  - Complement system is not activated in primary biliary cirrhosis.
AB  - There is controversial evidence suggesting that the classical pathway of
      complement system is chronically activated in primary biliary cirrhosis (PBC) and
      that complement activation may be important in development of bile duct injury.
      We have reevaluated this issue by measuring by-products of complement activation
      such as C4a, C3a, Bb, and terminal complement complexes (SC5b-9) in plasma of 44
      PBC patients with sensitive methods not previously used to detect complement
      activation in this disease. Age-matched healthy women and patients with chronic
      hepatitis of different etiology were studied as controls. We found that PBC
      patients have normal C4a concentrations. This finding argues strongly against
      chronic classical pathway activation. Although a minor increase of C3a levels was
      observed in a minority of PBC patients, the C3a/C3 ratio, an index used to
      evaluate the extent of native protein conversion, was remarkably similar in all
      groups. Potentially lytic terminal complement complexes were not increased. PBC
      patients had normal Bb plasma levels, indicating that the alternative pathway is
      also not activated. C3 concentration was higher in PBC patients than in healthy
      subjects and in chronic hepatitis patients, particularly in the early stages of
      the disease. C3 and C4 concentrations became lower in PBC and chronic hepatitis
      with the progression of the disease. The increase of C3 concentration in PBC does
      not reflect liver inflammation, since serum levels of C-reactive protein are
      normal. We found high serum C3 levels in patients with rare chronic cholestatic
      syndromes without superimposed infections and observed that serum C3 levels
      paralleled those of bilirubin in a patient with benign recurrent intrahepatic
      cholestasis. In conclusion, our data indicate that complement is not activated in
      PBC and that the increase of serum C3 levels is related to cholestasis.

PMID- 9646841
TI  - Human neutrophils express the prostaglandin G/H synthase 2 gene when stimulated
      with bacterial lipopolysaccharide.
AB  - Human blood neutrophils (PMN) rapidly release arachidonic acid (AA) from cellular
      phospholipids when stimulated in vitro with a variety of inflammatory agonists.
      Free AA is then metabolized via 5'-lipoxygenase to produce bioactive mediators
      such as leukotriene B4 and 5-hydroxyeicosatetraenoate. Arachidonic acid can also
      be metabolized via the cyclooxygenase or prostaglandin G/H synthase (PGHS)
      pathway to form prostaglandins and thromboxane. We show here that human blood PMN
      express the PGHS 2 gene when stimulated with bacterial lipopolysaccharide (LPS).
      PGHS 2 mRNA increases within 30 min after LPS stimulation and PGHS 2
      immunoreactive protein is detectable by 5 h. Although PGHS 1 mRNA is detectable
      in PMN, no immunoreactive protein is observed in either resting or LPS-stimulated
      cells. Following stimulation with LPS and expression of PGHS 2, PMN increase
      secretion of prostaglandin E2. This phenotypic change in PMN could be an
      important mechanism for regulating inflammation.

PMID- 9646842
TI  - IL-1 receptor antagonist (IL-1RA) gene polymorphism in Sjogren's syndrome and
      rheumatoid arthritis.
AB  - The gene encoding interleukin-1 receptor antagonist (IL-1ra) has a variable
      allelic polymorphism. The IL1RN*2 allele was recently described as a factor of
      severity in several autoimmune diseases and was paradoxically associated with
      increased production of IL-1ra by monocytes in vitro. We studied this
      polymorphism in 36 patients with possible or definite primary Sjogren's syndrome
      and found that IL1RN*2 was significantly more frequent in the definite than in
      the possible form. In rheumatoid arthritis, the frequency of the allele was not
      different from that of controls. The serum levels of IL-1ra were markedly higher
      in Sjogren patients than in those of healthy subjects. By contrast, the salivary
      IL-1ra levels were decreased. Patients with the allele generally had lower
      salivary levels and higher serum levels than patients without the allele. In the
      group of patients with the definite syndrome, CRP and TGF-beta 1, two in vitro
      stimulators of IL-1ra production, were correlated with IL-1ra serum levels. Our
      results suggest that IL1RN*2 is a marker of more severe forms of Sjogren's
      syndrome. Its effect on salivary and serum IL-1ra may be distinct, suggesting
      separate regulatory mechanisms.

PMID- 9646843
TI  - Molecular and cellular events in early thymocyte development.

PMID- 9646844
TI  - Regulation of immunoglobulin light chain isotype expression.

PMID- 9646845
TI  - Role of immunoreceptor tyrosine-based activation motif in signal transduction
      from antigen and Fc receptors.

PMID- 9646846
TI  - The atypical serine proteases of the complement system.

PMID- 9646847
TI  - Accessibility control of V(D)J recombination: lessons from gene targeting.

PMID- 9646848
TI  - Interactions between the immune system and gene therapy vectors: bidirectional
      regulation of response and expression.

PMID- 9646849
TI  - How do major histocompatibility complex genes influence odor and mating
      preferences?

PMID- 9646850
TI  - Olfactory receptor gene regulation.

PMID- 9646851
TI  - [Undertreatment of patients with pain has to be stopped. New therapeutic
      prospectives with retard tilin/naloxone].

PMID- 9646852
TI  - Modifications to the in situ TUNEL method for detection of apoptosis in paraffin
      embedded tissue sections.
AB  - The in situ detection of cells undergoing apoptosis is increasingly important in
      the analysis of injury and degeneration in the central nervous system. Limited
      information is presently available on the quantification of apoptosis in paraffin
      embedded brain tissue sections, a technique which would be most useful in the
      evaluation of archival tissue for diagnostic and experimental purposes. In this
      report, optimized conditions for tissue digestion and permeabilization using
      Proteinase K and Triton X and a quantification method for apoptosis detection are
      described using brain sections from aluminum maltolate-treated aged and young
      rabbits as compared to untreated matched controls. This method provides optimal
      staining of apoptotic cells without the problem of tissue destruction, and should
      prove useful in evaluating the process of apoptosis in neurodegenerative
      disorders.

PMID- 9646853
TI  - Expression of HER-2/neu oncogene in normal, hyperplastic, and malignant
      endometrium.
AB  - HER-2/neu oncogene is believed to be involved in tumorigenesis of several human
      malignancies. To assess the pattern of expression of this oncogene in normal,
      hyperplastic, and neoplastic endometrium, immunocytochemistry was applied to
      paraffin-embedded tissue sections obtained from 146 patients with endometrial
      adenocarcinoma. A spectrum of hyperplastic changes ranging from simple
      hyperplasia to atypical hyperplasia was seen in 15 percent (22/146) of cases.
      Expression for HER-2/neu oncogene was demonstrated as cell membrane staining.
      Normal, hyperplastic and neoplastic epithelial cells showed a heterogeneous
      expression for HER-2/neu oncogene. The intensity of the immunostaining and the
      number of cells stained for HER-2/neu oncogene had no significant association
      with surgical stage or histologic grade, although the proportion of patients
      demonstrating overexpression increased significantly as the histologic grade of
      their tumor increased (p = 0.030). Furthermore, in a multivariate analysis, a
      statistically significant correlation was found between the level of expression
      of HER-2/neu oncogene and overall survival (p = 0.025). This study demonstrated
      that HER-2/neu oncogene expression is variably present in normal and hyperplastic
      endometrium. Association between HER-2/neu oncogene expression, higher grade
      lesions and poor survival in patients with endometrial cancer may also justify
      assessment of HER-2/neu oncogene as a reliable prognostic indicator.

PMID- 9646854
TI  - Postmortem diagnosis of hemoglobin SC disease complicated by fat embolism.
AB  - A case is reported of a previously healthy 52-year-old African American male who
      presented with acute onset of abdominal pain. Progressive increase in his
      abdominal symptoms led to an exploratory laparotomy; however, no pathology was
      discovered. Postoperatively, the patient became hypoxemic which progressed to
      diffuse infiltrates on chest x-ray, suggestive of adult respiratory distress
      syndrome. He had a rapidly fatal course. Autopsy showed bone marrow infarction,
      fat embolism, splenomegaly, and widespread congestion with sickle erythrocytes.
      Hemoglobin electrophoresis done postmortem showed hemoglobin (Hb) SC disease that
      was undiagnosed antemortem. To the best of our knowledge, it is unusual for Hb SC
      to be diagnosed postmortem in adults. This case suggests that sickle cell
      disorders should be ruled out in patients at risk for hemoglobinopathy in the
      presence of signs and symptoms compatible with the disease, irrespective of age.

PMID- 9646855
TI  - HLA-Dr negative acute non-lymphocytic leukemia.
AB  - Absent or diminished HLA-Dr antigen representation on the cell surface of both
      normal and leukemic promyelocytes is a hallmark of this stage of myeloid
      maturation. In order to document the specificity of this finding for acute
      promyelocytic leukemia, flow cytometric analysis of leukemic blasts was utilized
      on 36 cases of acute non-lymphocytic leukemia. All 15 of the promyelocytic
      leukemias (FAB-M3) studied showed absent or markedly decreased HLA-Dr antigen on
      their cell surface. However, the majority of cases (21) in which this finding was
      noted were other than promyelocytic leukemias and included all FAB subtypes, most
      particularly FAB-M2, i.e., myeloblastic leukemia with maturation. It is concluded
      that absent to decreased HLA-Dr antigen representation on leukemic blasts lacks
      specificity and can be seen in all acute myeloid/monocytic leukemic subtypes.

PMID- 9646856
TI  - Phospholipid-independent binding of beta 2glycoprotein I by IgA from patients
      with antiphospholipid syndrome.
AB  - beta 2glycoprotein I (beta 2GPI) is a phospholipid-binding protein of the
      coagulation system. In patients with the antiphospholipid syndrome (APS),
      antibodies to beta 2GPI contribute to the population of "antiphospholipid
      antibodies" measured in the anticardiolipin antibody (aCL) assay. In fact, both
      IgG and IgM antibodies from patients with APS bind beta 2GPI in the absence of
      anionic phospholipids if the antigen is bound to a suitable surface, i.e., one
      which exposes the epitope. The binding of IgA was studied from patients with APS,
      using an enzyme-linked immunosorbent assay (ELISA), and significantly higher
      binding of IgA was observed from 39 patients compared to a control group of 50
      healthy individuals (p < 0.0001). Moreover, 15 out of 39 APS subjects (38
      percent) exhibited binding greater than 5 standard deviations (SD) above the mean
      of the control group. All 39 APS patients had elevated IgG anti-beta 2GPI;
      however, depletion of IgG from two APS sera diminished, rather than enhanced,
      binding of IgA. Pre-incubation with purified IgG from a subject with APS led to
      inhibition of IgA binding at inhibitor levels > 125 micrograms IgG/well. These
      data demonstrate that patients with APS have IgA anti-beta 2GPI autoantibodies
      and that the epitope(s) which are recognized by these antibodies can be presented
      in the absence of cardiolipin or other anionic phospholipids.

PMID- 9646857
TI  - Stability of cannabinoids in urine in three storage temperatures.
AB  - Stability of cannabinoid compounds in urine samples were evaluated using several
      storage temperatures. Appreciable losses (> 22.4 percent) were observed in some
      urine samples, after being stored at room temperature for 10 days. Lower losses
      (8.1 percent) were observed when the urine samples were refrigerated for 4 weeks.
      The behavior of urine samples depended on the analyzed urine. This could be due
      to the different stability of the cannabinoids present in each urine sample.
      Important losses of 8.0 +/- 10.6, 15.8 +/- 4.2, and 19.6 +/- 6.7 percent were
      found when the urine samples were frozen during 40 days, 1 year, and 3 years,
      respectively. Average losses (> > 5 percent) can be observed after one day which
      could mainly be due to the decrease of the solubility of 11-nor-U9
      tetrahydrocannabinol-9-carboxylic acid (THC-COOH) or adsorption process of
      cannabinoid molecules to the plastic storage containers.

PMID- 9646858
TI  - Long-term maintenance of immunity in patients with common variable immune
      deficiency by plasma transfusion.
AB  - The AIDS crisis and the fear of blood product contamination stimulated the
      development of a designated plasma collection and transfusion for patients with
      common variable immune deficiency. Four patients have been maintained over 1
      year; 5 years and 10 months; 8 years and 7 months; and 12 years. A new crisis
      affecting commercial IgG manufacturing, owing to recalls, has made the life
      saving product scarce, threatening patients' health maintenance. Our experience
      over a long time has demonstrated that plasma transfusion is equivalent to
      management with commercial IgG. The program of product collection and patient
      management includes testing the collected plasma for IgG content, selecting ABO
      compatible plasma, and following patients with IgG trough levels, prior to each
      transfusion, to assure sufficient immune globulin administration.

PMID- 9646859
TI  - The incidence of elevations in urine 5-hydroxyindoleacetic acid.
AB  - A 24-hour urine collection for 5-hydroxyindoleacetic acid (HIAA) is commonly
      performed to evaluate patients with suspected carcinoid syndrome. However,
      carcinoids are rare, and elevated results are common even when using an
      analytically specific method. To characterize this problem, the incidence of
      elevated results was examined in a population of 947 patient specimens received
      in a clinical reference laboratory setting. Using a reference limit of 15 mg/d
      identified 7.9 percent of the results as elevated, with 3 percent > 100 mg/d, and
      about 1 percent > 350 mg/d. Males showed 14 percent > 15 mg/d compared to 5.2
      percent for females. Characterization of incomplete and excess 24-hr urine
      collections is facilitated by use of a creatinine ratio, with a reference limit
      of 14 mg/g creatinine equivalent to 15 mg/d. Given the frequency of elevated
      results, HIAA should be used to support the diagnoses of carcinoid only when
      consistent with other objective findings.

PMID- 9646860
TI  - The stereochemical mechanism of the cooperative effects in hemoglobin revisited.
AB  - In 1970, Perutz tried to put the allosteric mechanism of hemoglobin, proposed by
      Monod, Wyman and Changeux in 1965, on a stereochemical basis. He interpreted
      their two-state model in terms of an equilibrium between two alternative
      structures, a tense one (T) with low oxygen affinity, constrained by salt-bridges
      between the C-termini of the four subunits, and a relaxed one (R) lacking these
      bridges. The equilibrium was thought to be governed primarily by the positions of
      the iron atoms relative to the porphyrin: out-of-plane in five-coordinated, high
      spin deoxyhemoglobin, and in-plane in six-coordinated, low-spin oxyhemoglobin.
      The tension exercised by the salt-bridges in the T-structure was to be
      transmitted to the heme-linked histidines and to restrain the movement of the
      iron atoms into the porphyrin plane that is necessary for oxygen binding. At the
      beta-hemes, the distal valine and histidine block the oxygen-combining site in
      the T-structure; its tension was thought to strengthen that blockage. Finally,
      Perutz attributed the linearity of proton release with early oxygen uptake to the
      sequential rupture of salt-bridges in the T-structure and to the accompanying
      drop in pKa of the weak bases that form part of them. Almost every feature of
      this mechanism has been disputed, but evidence that has come to light more than
      25 years later now shows it to have been substantially correct. That new evidence
      is reviewed below.

PMID- 9646861
TI  - The three-dimensional structure of the ribosome and its components.
AB  - Exciting progress has been made in the last decade by those who use physical
      methods to study the structure of the ribosome and its components. The structures
      of 10 ribosomal proteins and three isolated ribosomal protein domains are known,
      and the conformations of a significant number of rRNA sequences have been
      determined. Electron microscopists have made major advances in the analysis of
      images of ribosomes, and microscopically derived ribosome models at resolutions
      approaching 10A are likely quite soon. Furthermore, ribosome crystallographers
      are on the verge of phasing the diffraction patterns they have had for several
      years, and near-atomic resolution models for entire ribosomal subunits could
      emerge from this source at any time. The literature relevant to these
      developments is reviewed below.

PMID- 9646862
TI  - Signaling complexes: biophysical constraints on intracellular communication.
AB  - This review surveys the kinds of protein complex that participate in cell
      communication and identifies, where possible, general principles by which they
      form and act. It also advances the notion that biophysical constraints imposed by
      macromolecular crowding and diffusion have had a controlling influence on the
      evolution of cell signaling pathways. Complexes associated with the bacterial
      aspartate receptor, with eucaryotic tyrosine kinase receptors, with T-cell
      receptors, and with focal contacts are examined together with proteins that serve
      as adaptors, anchors, and scaffolds for signaling complexes. The importance of
      diffusion in controlling the numbers and locations of signaling complexes is
      discussed, as is the special role played by membranes in signaling pathways.

PMID- 9646863
TI  - Spatio-temporal resolution of exocytosis from individual cells.
AB  - Biophysical events involved in late stages of exocytosis occur at highly
      localized areas of cells on millisecond and submillisecond time scales. Thus,
      methodologies with high spatio-temporal resolution are required to achieve
      measurements at individual secretory cells. Much has been learned about the
      mechanisms and kinetics of vesicular release through analysis with the carbon
      fiber microelectrode techniques amperometry and cyclic voltammetry. Coupling of
      these techniques with other methods such as patch-clamp continues to reveal
      details of the secretion process. It is now clear that extrusion of the vesicular
      contents is a more complex process than previously believed. Vesicle-cell fusion,
      revealed by cell capacitance measurements, is temporally dissociated from
      secretion measured amperometrically. The stability imparted by interaction and
      association of vesicle contents at rest results in a rate-limiting extrusion
      process after full fusion. Furthermore, the presence of partial fusion events and
      the occurrence of nonquantized release have been revealed with electrochemical
      tools.

PMID- 9646864
TI  - Minor groove-binding architectural proteins: structure, function, and DNA
      recognition.
AB  - To date, high-resolution structures have been solved for five different
      architectural proteins complexed to their DNA target sites. These include TATA
      box-binding protein, integration host factor (IHF), high mobility group I(Y)[HMG
      I(Y)], and the HMG-box-containing proteins SRY and LEF-1. Each of these proteins
      interacts with DNA exclusively through minor groove contacts and alters DNA
      conformation. This paper reviews the structural features of these complexes and
      the roles they play in facilitating assembly of higher-order protein-DNA
      complexes and discusses elements that contribute to sequence-specific recognition
      and conformational changes.

PMID- 9646865
TI  - The structure and mechanism of protein phosphatases: insights into catalysis and
      regulation.
AB  - Eukaryotic protein phosphatases are structurally and functionally diverse enzymes
      that are represented by three distinct gene families. Two of these, the PPP and
      PPM families, dephosphorylate phosphoserine and phosphothreonine residues,
      whereas the protein tyrosine phosphatases (PTPs) dephosphorylate phosphotyrosine
      amino acids. A subfamily of the PTPs, the dual-specificity phosphatases,
      dephosphorylate all three phosphoamino acids. Within each family, the catalytic
      domains are highly conserved, with functional diversity endowed by regulatory
      domains and subunits. The protein Ser/Thr phosphatases are metalloenzymes and
      dephosphorylate their substrates in a single reaction step using a metal
      activated nucleophilic water molecule. In contrast, the PTPs catalyze
      dephosphorylation by use of a cysteinyl-phosphate enzyme intermediate. The
      crystal structures of a number of protein phosphatases have been determined,
      enabling us to understand their catalytic mechanisms and the basis for substrate
      recognition and to begin to provide insights into molecular mechanisms of protein
      phosphatase regulation.

PMID- 9646866
TI  - Biosensors in chemical separations.
AB  - Identification of biomolecules in complex biological mixtures represents a major
      challenge in biomedical, environmental, and chemical research today. Chemical
      separations with traditional detection schemes such as absorption, fluorescence,
      refractive index, conductivity, and electrochemistry have been the standards for
      definitive identifications of many compounds. In many instances, however, the
      complexity of the biomixture exceeds the resolution capability of chemical
      separations. Biosensors based on molecular recognition can dramatically improve
      the selectivity of and provide biologically relevant information about the
      components. This review describes how coupling chemical separations with online
      biosensors solves challenging problems in sample analysis by identifying
      components that would not normally be detectable by either technique alone. This
      review also presents examples and principles of combining chemical separations
      with biosensor detection that uses living systems, whole cells, membrane
      receptors, enzymes, and immunosensors.

PMID- 9646867
TI  - Simulation of prokaryotic genetic circuits.
AB  - Biochemical and genetic approaches have identified the molecular mechanisms of
      many genetic reactions, particularly in bacteria. Now a comparably detailed
      understanding is needed of how groupings of genes and related protein reactions
      interact to orchestrate cellular functions over the cell cycle, to implement
      preprogrammed cellular development, or to dynamically change a cell's processes
      and structures in response to environmental signals. Simulations using realistic,
      molecular-level models of genetic mechanisms and of signal transduction networks
      are needed to analyze dynamic behavior of multigene systems, to predict behavior
      of mutant circuits, and to identify the design principles applicable to design of
      genetic regulatory circuits. When the underlying design rules for regulatory
      circuits are understood, it will be far easier to recognize common circuit
      motifs, to identify functions of individual proteins in regulation, and to
      redesign circuits for altered functions.

PMID- 9646868
TI  - DNA nanotechnology: novel DNA constructions.
AB  - DNA nanotechnology entails the construction of specific geometrical and
      topological targets from DNA. The goals include the use of DNA molecules to
      scaffold the assembly of other molecules, particularly in periodic arrays, with
      the objects of both crystal facilitation and memory-device construction. Many of
      these products are based on branched DNA motifs. DNA molecules with the
      connectivities of a cube and a truncated octahedron have been prepared. A solid
      support methodology has been developed to construct DNA targets. DNA trefoil and
      figure-8 knots have been made, predicated on the relationship between a
      topological crossing and a half-turn of B-DNA or Z-DNA. The same basis has been
      used to construct Borromean rings from DNA. An RNA knot has been used to
      demonstrate an RNA topoisomerase activity. The desire to construct periodic
      matter held together by DNA sticky ends has resulted in a search for stiff
      components; DNA double crossover molecules appear to be the best candidates. It
      appears that novel DNA motifs may be of use in the new field of DNA-based
      computing.

PMID- 9646869
TI  - Inhibitors of HIV-1 protease: a major success of structure-assisted drug design.
AB  - Retroviral protease (PR) from the human immunodeficiency virus type 1 (HIV-1) was
      identified over a decade ago as a potential target for structure-based drug
      design. This effort was very successful. Four drugs are already approved, and
      others are undergoing clinical trials. The techniques utilized in this remarkable
      example of structure-assisted drug design included crystallography, NMR,
      computational studies, and advanced chemical synthesis. The development of these
      drugs is discussed in detail. Other approaches to designing HIV-1 PR inhibitors,
      based on the concepts of symmetry and on the replacement of a water molecule that
      had been found tetrahedrally coordinated between the enzyme and the inhibitors,
      are also discussed. The emergence of drug-induced mutations of HIV-1 PR leads to
      rapid loss of potency of the existing drugs and to the need to continue the
      development process. The structural basis of drug resistance and the ways of
      overcoming this phenomenon are mentioned.

PMID- 9646870
TI  - Structure, dynamics, and function of chromatin in vitro.
AB  - The substrates for the essential biological processes of transcription,
      replication, recombination, DNA repair, and cell division are not naked DNA;
      rather, they are protein-DNA complexes known as chromatin, in one or another
      stage of a hierarchical series of compactions. These are exciting times for
      students of chromatin. New studies provide incontrovertible evidence linking
      chromatin structure to function. Exceptional progress has been made in studies of
      the structure of chromatin subunits. Surprising new dynamic properties have been
      discovered. And, much progress has been made in dissecting the functional roles
      of specific chromatin proteins and domains. This review focuses on in vitro
      studies of chromatin structure, dynamics, and function.

PMID- 9646871
TI  - Cytochrome c oxidase: structure and spectroscopy.
AB  - Cytochrome c oxidase, the terminal enzyme of the respiratory chains of
      mitochondria and aerobic bacteria, catalyzes electron transfer from cytochrome c
      to molecular oxygen, reducing the latter to water. Electron transfer is coupled
      to proton translocation across the membrane, resulting in a proton and charge
      gradient that is then employed by the F0F1-ATPase to synthesize ATP. Over the
      last years, substantial progress has been made in our understanding of the
      structure and function of this enzyme. Spectroscopic techniques such as EPR,
      absorbance and resonance Raman spectroscopy, in combination with site-directed
      mutagenesis work, have been successfully applied to elucidate the nature of the
      cofactors and their ligands, to identify key residues involved in proton
      transfer, and to gain insight into the catalytic cycle and the structures of its
      intermediates. Recently, the crystal structures of a bacterial and a
      mitochondrial cytochrome c oxidase have been determined. In this review, we
      provide an overview of the crystal structures, summarize recent spectroscopic
      work, and combine structural and spectroscopic data in discussing mechanistic
      aspects of the enzyme. For the latter, we focus on the structure of the oxygen
      intermediates, proton-transfer pathways, and the much-debated issue of how
      electron transfer in the enzyme might be coupled to proton translocation.

PMID- 9646872
TI  - The use of 2H, 13C, 15N multidimensional NMR to study the structure and dynamics
      of proteins.
AB  - During the past thirty years, deuterium labeling has been used to improve the
      resolution and sensitivity of protein NMR spectra used in a wide variety of
      applications. Most recently, the combination of triple resonance experiments and
      2H, 13C, 15N labeled samples has been critical to the solution structure
      determination of several proteins with molecular weights on the order of 30 kDa.
      Here we review the developments in isotopic labeling strategies, NMR pulse
      sequences, and structure-determination protocols that have facilitated this
      advance and hold promise for future NMR-based structural studies of even larger
      systems. As well, we detail recent progress in the use of solution 2H NMR methods
      to probe the dynamics of protein sidechains.

PMID- 9646873
TI  - RNA recognition by RNP proteins during RNA processing.
AB  - The ribonucleoprotein (RNP) domain is one of the most common eukaryotic protein
      folds. Proteins containing RNP domains function in important steps of
      posttranscriptional regulation of gene expression by directing the assembly of
      multiprotein complexes on primary transcripts, mature mRNAs, and stable
      ribonucleoprotein components of the RNA processing machinery. The diverse
      functions performed by these proteins depend on their dual ability to recognize
      RNA and to interact with other proteins, often utilizing specialized auxiliary
      domains. Crystallographic and NMR structures of several RNP domains and a handful
      of structures of RNA-protein complexes have begun to reveal the molecular basis
      for RNP-RNA recognition.

PMID- 9646874
TI  - On the characteristics of functional magnetic resonance imaging of the brain.
AB  - In this review we discuss various recent topics that characterize functional
      magnetic resonance imaging (fMRI). These topics include a brief description of
      MRI image acquisition, how to cope with noise or signal fluctuation, the basis of
      fMRI signal changes, and the relation of MRI signal to neuronal events. Several
      observations of fMRI that show good correlation to the neurofunction are referred
      to. Temporal characteristics of fMRI signals and examples of how the feature of
      real time measurement is utilized are then described. The question of spatial
      resolution of fMRI, which must be dictated by the vascular structure serving the
      functional system, is discussed based on various fMRI observations. Finally, the
      advantage of fMRI mapping is shown in a few examples. Reviewing the vast number
      of recent fMRI application that have now been reported is beyond the scope of
      this article.

PMID- 9646875
TI  - Crystallographic structures of the hammerhead ribozyme: relationship to ribozyme
      folding and catalysis.
AB  - The hammerhead ribozyme is a small catalytic RNA that cleaves a target
      phosphodiester bond in a reaction dependent on divalent metal ions. Crystal
      structures of the hammerhead reveal the tertiary fold of an enzymatic "ground
      state" of the molecule; however, they do not clarify the catalytic mechanism of
      the ribozyme, presumably because a significant conformational rearrangement is
      required to reach an enzymatic transition state. The structural domains seen in
      the hammerhead can be related to sequence or structural motifs in transfer and
      ribosomal RNAs, suggesting that they represent tertiary building blocks that will
      be found in large, complex RNAs.

PMID- 9646876
TI  - Pleckstrin homology domains: a common fold with diverse functions.
AB  - Pleckstrin homology (PH) motifs are approximately 100 amino-acid residues long
      and have been identified in nearly 100 different eukaryotic proteins, many of
      which participate in cell signaling and cytoskeletal regulation. Despite minimal
      sequence homology, the three-dimensional structures are remarkably conserved.
      This review gives an overview of the PH domain architecture and examines the best
      studied examples in an attempt to understand their function.

PMID- 9646877
TI  - What do antidepressant effects on sleep tell us about pathways to treatment
      response?

PMID- 9646878
TI  - Comparative effects of nefazodone and fluoxetine on sleep in outpatients with
      major depressive disorder.
AB  - BACKGROUND: Sleep disturbances are common in major depressive disorder. In
      previous open-label trials, nefazodone improved sleep continuity and increased
      rapid eye movement (REM) sleep, while not affecting stage 3/4 sleep or REM
      latency: in contrast, fluoxetine suppressed REM sleep. This study compared the
      objective and subjective effects of nefazodone and fluoxetine on sleep. METHODS:
      This paper reports combined results of three identical, multisite, randomized,
      double-blind, 8-week, acute-phase trials comparing nefazodone (n = 64) with
      fluoxetine (n = 61) in outpatients with nonpsychotic major depressive disorder
      and insomnia. Sleep electroencephalographic (EEG) recordings were gathered at
      baseline and weeks 2, 4, and 8. Clinical ratings were obtained at weeks 1-4, 6,
      and 8. RESULTS: Nefazodone and fluoxetine were equally effective in reducing
      depressive symptoms; however, nefazodone differentially and progressively
      increased (while fluoxetine reduced) sleep efficiency and reduced (while
      fluoxetine increased) the number of awakenings in a linear fashion over the 8
      week trial. Fluoxetine, but not nefazodone, prolonged REM latency and suppressed
      REM sleep. Nefazodone significantly increased total REM sleep time. Clinical
      evaluations of sleep quality were significantly improved with nefazodone compared
      with fluoxetine. CONCLUSIONS: Nefazodone and fluoxetine were equally effective
      antidepressants. Nefazodone was associated with normal objective, and clinician-
      and patient-rated assessments of sleep when compared with fluoxetine. These
      differential sleep EEG effects are consistent with the notion that nefazodone and
      fluoxetine may have somewhat different modes and spectra of action.

PMID- 9646879
TI  - Plasma corticotropin-releasing factor in depressive disorders.
AB  - BACKGROUND: The aim of this work was to investigate alterations of plasma
      corticotropin-releasing factor (CRF) levels in depressive states. We have also
      measured plasma cortisol and corticotropin (ACTH) concentrations and examined
      their correlation with the peripheral CRF values. METHODS: Thirty-six outpatients
      from the psychiatric department of a Barcelona hospital who were diagnosed as
      having major depressive disorder (n = 26) and dysthymic depressive disorder (n =
      10) were studied. Among the major depressed patients, 10 suffered from severe
      depressive disorder and 16 from mild or moderate depressive disorder. The
      comparison group consisted of 17 healthy volunteers. Cortisol, ACTH, and CRF
      concentrations were determined by iodine-125 radioimmunoassay; CRF measurements
      were performed on C18 extracted samples. RESULTS: CRF and cortisol plasma
      concentrations were significantly higher in major depression and dysthymia than
      in the comparison group. The major depressed patients did not show significantly
      different CRF and cortisol levels than the dysthymic. Severe major depressive
      disorder exhibited significantly higher CRF plasma levels than the mild or
      moderate episodes. Plasma cortisol and CRF concentrations correlated
      significantly. CONCLUSIONS: The results obtained indicate that plasma CRF values
      are altered in depressive disorders and suggest that these determinations could
      be important for understanding the pathophysiology in affective illness.

PMID- 9646880
TI  - Sleep electroencephalographic response to muscarinic and serotonin1A receptor
      probes in patients with major depression and in normal controls.
AB  - BACKGROUND: To test the hypothesis that depression is associated with an
      increased ratio of cholinergic to serotonergic neurotransmission, we compared the
      effects of pilocarpine, a muscarinic agonist, and ipsapirone, a serotonin (5
      HT)1A agonist, on electroencephalographic (EEG) sleep in depressed and healthy
      subjects. We hypothesized, adopting the reciprocal interaction model, that the
      effects on REM sleep of these probes within the same individuals are negatively
      correlated and unmask neurobiological changes in depression. METHODS:
      Polysomnographic recordings were obtained in 12 unmedicated patients with a
      current major depression and 12 normal controls. They received placebo,
      pilocarpine 25 mg, or ipsapirone 10 mg (orally, 15 min before bedtime, after
      premedication with the peripheral anticholinergic probanthine 30 mg, double
      blind, counterbalanced) on three occasions. RESULTS: Pilocarpine shortened and
      ipsapirone prolonged REM latency equally in both groups. These effects were not
      correlated. Pilocarpine decreased slow-wave sleep and EEG delta power during the
      first nonREM episode more in controls than in patients, and enhanced EEG sigma
      power equally in both groups. Ipsapirone had no significant effects on EEG power.
      CONCLUSION: These data do not support the postulate of muscarinic receptor up
      regulation and 5-HT1A receptor down-regulation in depression. The significance of
      blunted delta power suppression in patients following pilocarpine warrants
      further investigations.

PMID- 9646881
TI  - Structural and functional abnormalities in elderly patients clinically recovered
      from early- and late-onset depression.
AB  - BACKGROUND: Structural and functional brain changes have been described in
      elderly patients with unipolar affective disorder. Changes appear to be more
      marked in patients with late-onset depression, but the reversibility of such
      changes after clinical recovery is not known. METHODS: Magnetic resonance
      imaging, electroencephalography (EEG), and cognitive tests were performed in 23
      elderly patients (mean age 66.5 years) clinically recovered from major
      depression. Twelve had late-onset depression (first episode over 55 years of
      age); 11 had early onset (first episode before 50 years). EEG and cognitive
      testing were also performed on 15 control subjects. RESULTS: Patients with late
      onset depression had larger third and lateral ventricles, increased ventricular
      brain ratio, and greater frequency and severity of subcortical white matter
      lesions than those with early onset. There was no difference between early- and
      late-onset patients in EEG and cognitive measures, but compared with controls
      patients showed significant changes in EEG evoked potentials and increased slow
      wave activity, slowed reaction times, and global impairments in cognitive
      function. CONCLUSIONS: These results suggest that structural changes are greater
      in patients with late-onset depression, and that EEG and cognitive impairments
      persist after recovery, regardless of age of onset of depression, and are
      independent of structural changes.

PMID- 9646882
TI  - Evidence for an allelic association between bipolar disorder and a Na+, K+
      adenosine triphosphatase alpha subunit gene (ATP1A3).
AB  - BACKGROUND: Disturbances in central nervous system Na+, K+ adenosine
      triphosphatase (ATPase) activity have previously been proposed as being involved
      in the pathophysiology of bipolar mood disorder. METHODS: We have examined one
      particular alpha subunit of this enzyme for allelic association in a sample of 85
      Irish bipolar patients and 85 matched controls. RESULTS: There was evidence for
      an overall allelic association between the disease and a dinucleotide
      polymorphism within the ATP1A3 gene (p = .022). Subjects were then analyzed on
      the basis of a number of criteria, and the significance of the association
      increased when cases were divided based on the nature of the first episode.
      Patients who presented with a depressive episode first showed a significant
      association (p = .001) with this polymorphism. CONCLUSIONS: The results presented
      here provide preliminary evidence of an association between bipolar disorder and
      an alpha subunit of Na+, K+ ATPase, the expression of which predominates in the
      brain.

PMID- 9646883
TI  - Effect of transcranial magnetic stimulation in posttraumatic stress disorder: a
      preliminary study.
AB  - BACKGROUND: Transcranial magnetic stimulation (TMS) has become, over the last few
      years, a promising avenue for new research in affective disorders. In this study
      we have evaluated the clinical effect of slow TMS on posttraumatic stress
      disorder (PTSD) symptoms. METHODS: Ten PTSD patients were given one session of
      slow TMS with 30 pulses of 1 m/sec each, 15 to each side of the motor cortex.
      RESULTS: Symptoms of PTSD were assessed by using three psychological assessment
      scales, at four different time points. In this first, pilot, open study, TMS was
      found to be effective in lowering the core symptoms of PTSD: avoidance (as
      measured by the Impact of Event Scale), anxiety, and somatization (as measured by
      the Symptom Check List-90). A general clinical improvement was found (as measured
      by the Clinical Global Impression scale); however, the effect was rather short
      and transient. CONCLUSIONS: The present study showed TMS to be a safe and
      tolerable intervention with possibly indications of therapeutic efficacy for PTSD
      patients.

PMID- 9646884
TI  - Plasma norepinephrine and 3-methoxy-4-hydroxyphenylglycol concentrations and
      severity of depression in combat posttraumatic stress disorder and major
      depressive disorder.
AB  - BACKGROUND: Catecholamines are thought to play a significant role in the
      pathophysiology of posttraumatic stress disorder (PTSD), but findings in PTSD
      have been discrepant. METHODS: To obtain more information about catecholamine
      activity in PTSD, we sampled plasma norepinephrine (NE) and 3-methoxy-4
      hydroxyphenylglycol (MHPG) concentrations over a 24-hour period in men with PTSD
      (n = 15) and major depressive disorder (MDD) (n = 12), and nonpsychiatric
      comparison subjects (n = 13), under unstimulated conditions. Chronobiological
      analyses were performed to determine possible changes in the circadian and
      ultradian release of these hormones. RESULTS: Significant group differences were
      present for mean plasma NE levels (p = .03), but not MHPG. NE levels were
      significantly associated with severity of depression in the PTSD group (p =
      .002). Therefore, PTSD subjects were further subdivided into those with and
      without a comorbid secondary depression. Increased NE levels were only present in
      PTSD subjects who did not have a secondary depression. This study also found no
      significant group differences on any of the chronobiological parameters.
      CONCLUSIONS: The results clarify that increased NE levels in PTSD may be confined
      to the subgroup of subjects who do not have comorbid depression, and as such, may
      help resolve some of the discrepancies in the literature regarding basal
      catecholamine activity.

PMID- 9646885
TI  - Alprazolam reduces response to loud tones in panic disorder but not in
      posttraumatic stress disorder.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) and panic disorder (PD) share
      several clinical features, and theory postulates that phasic arousal is similarly
      dysregulated in both. The modulation of phasic arousal can be probed by measuring
      the effect of pharmacologic agents on auditory startle. METHODS: Eyeblink
      electromyogram, heart rate, and skin conductance (SC) responses to 15 consecutive
      presentations of 1000-Hz, 95-dB, zero rise-time pure tones were measured, before
      and during treatment with alprazolam, in 9 PTSD and 9 PD patients. Concurrent
      anxiety was assessed by the Hamilton Anxiety Rating Scale. RESULTS: The groups
      did not differ in initial psychometric and physiological measures. Significant
      decrease in anxiety was observed in both groups during treatment. A decrease in
      response probability and a decrease in the SC responses were observed in PD, but
      not in PTSD. CONCLUSIONS: The results may reflect a difference in the modulation
      of phasic arousal between the disorders. They may also express an impaired
      between-session habituation or contextual sensitization in PTSD.

PMID- 9646886
TI  - Hypnotizability, pain threshold, and dissociative experiences.
AB  - BACKGROUND: There may be an association between pain threshold, hypnotizability,
      and dissociative experiences. The purpose of the present study was to examine
      this association. METHODS: Forty-one healthy subjects were included in the study.
      Pain thresholds were determined using a manual algometer. The Dissociative
      Experiences Scale was administered to all subjects. Hypnotizability of the
      subjects was assessed by the eye roll sign of the Hypnotic Induction Profile.
      There were 14, 15, and 12 subjects in the Grade 1, 2, and 3 groups, respectively.
      RESULTS: Highly hypnotizable subjects had lower pain thresholds and were more
      likely to report dissociative experiences than the less hypnotizable subjects.
      CONCLUSIONS: There is an association between pain threshold, hypnotizability, and
      dissociative experiences. It may be suggested that dissociative and somatic
      symptoms may be integrally linked and related to hypnotic suggestibility.

PMID- 9646887
TI  - Attention-deficit hyperactivity disorder and the stress response.
AB  - BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is a developmental
      disorder whose three main symptoms are impulsiveness, inattention, and
      hyperactivity. Researchers have proposed that the central deficit in ADHD is one
      of poor response inhibition. The present studies were designed to look at the
      functioning of the hypothalamic-pituitary-adrenal (HPA) axis in response to
      mental stress in aggressive ADHD subjects participating in a longitudinal study
      of various psychosocial treatments. METHODS: Pretest and posttest morning
      salivary samples for cortisol determination were collected from subjects given a
      battery of tests. RESULTS: The study shows that ADHD subjects who maintained
      their diagnosis over the first year of the study had a blunted response to the
      stressor in comparison to those ADHD subjects who no longer retained the disorder
      1 year later. CONCLUSIONS: The data suggest that an impaired response to stress
      may be a marker for the more developmentally persistent form of the disorder.

PMID- 9646888
TI  - Selective serotonin reuptake inhibitor elimination half-lives: the long and the
      short of it.

PMID- 9646889
TI  - Selective serotonin reuptake inhibitor discontinuation syndrome: a randomized
      clinical trial.
AB  - BACKGROUND: Recent reports describe discontinuation-emergent adverse events upon
      cessation of selective serotonin reuptake inhibitors including dizziness,
      insomnia, nervousness, nausea, and agitation. We hypothesized that interruption
      of fluoxetine treatment would be associated with fewer discontinuation-emergent
      adverse events than interruption of sertraline or paroxetine treatment, based on
      fluoxetine's longer half-life. METHODS: In this 4-week study, 242 patients with
      remitted depression receiving maintenance therapy with open-label fluoxetine,
      sertraline, or paroxetine for 4-24 months had their maintenance therapy
      interrupted with double-blind placebo substitution for 5-8 days. The Symptom
      Questionnaire (SQ), the Discontinuation-Emergent Signs and Symptoms checklist,
      the 28-item Hamilton Depression Rating Scale, and the Montgomery-Asberg
      Depression Rating Scale were used to assess somatic distress and stability of
      antidepressant response. RESULTS: Two hundred twenty patients (91%) completed the
      study. Following interruption of therapy, fluoxetine-treated patients experienced
      fewer discontinuation-emergent events than either sertraline-treated or
      paroxetine-treated patients (p < .001). The mean SQ somatic symptom scale score
      in fluoxetine-treated patients was significantly lower than that in sertraline
      treated and paroxetine-treated patients (p < .001). Fluoxetine-treated patients
      also experienced less reemergence of depressive symptoms than sertraline-treated
      or paroxetine-treated patients (p < .001). CONCLUSIONS: Abrupt interruption of
      antidepressant therapy for 5-8 days was associated with the emergence of new
      somatic and psychological symptoms in patients treated with paroxetine and to a
      lesser degree sertraline, with few symptoms seen with fluoxetine.

PMID- 9646890
TI  - A reduction of nonpyramidal cells in sector CA2 of schizophrenics and manic
      depressives.
AB  - BACKGROUND: Recent studies have suggested that there may be a preferential
      decrease of "nonpyramidal" neurons (NPs) in several corticolimbic regions of
      schizophrenic (SZ) brain. The current study was undertaken to determine whether a
      change in the density of pyramidal neurons (PNs) and NPs might be present in the
      hippocampal formation (HIPP) of SZ brain. METHODS: A spatial counting approach in
      which the location of each and every PN and NP in the stratum pyramidale of
      sectors CA1-4 was applied to 11 normal control (CONs) and 10 SZs matched for age
      and postmortem interval, as well as 4 manic depressive (MD) subjects matched for
      age. RESULTS: The data indicate that the CONs had approximately 10-20 times as
      many PNs than NPs in the various HIPP subfields. When the CON data were compared
      to those for the SZs, both the total number and density of PNs were found to be
      similar in all four sectors, while NPs were found to be selectively reduced by
      approximately 40% in CA2 of the SZ group. When the data were broken down
      according to patients with and without neuroleptic exposure, drug-free SZs showed
      a significant reduction in the density of NPs in CA2. The 4 MD cases both with
      and without neuroleptic exposure also showed a similar reduction of NPs in sector
      CA2. CONCLUSIONS: Taken together, the results of this study suggest that there
      may be a highly selective decrease in the number of NPs in sector CA2 that could
      play a contributory role in the pathophysiology of the major psychoses.

PMID- 9646891
TI  - Nicotinic receptor desensitization and sensory gating deficits in schizophrenia.
AB  - BACKGROUND: Nicotinic receptor dysfunction is a possible mechanism of the
      abnormal sensory gating observed in schizophrenia with the P50 auditory event
      related potential. Although nicotinic receptors normally desensitize after
      activation by acetylcholine or nicotine, pathologically increased desensitization
      might cause receptor dysfunction in schizophrenia. To examine this possibility,
      central cholinergic neuronal activity was diminished by allowing schizophrenic
      patients to sleep briefly, after which they experienced a transient period of
      normal P50 gating, consistent with receptor resensitization during the absence of
      cholinergic stimulation. A critical test of the mechanism is whether this
      resensitization is blocked by concurrent administration of nicotine, which would
      provide continuous receptor stimulation. METHODS: Six schizophrenic patients
      repeated the sleep experiment during nicotine exposure from a dermal patch, in a
      double-blind, placebo-controlled design. RESULTS: The normalization of P50 gating
      immediately postsleep was replicated in the placebo arm, but this effect was
      decreased in all six patients during exposure to nicotine. CONCLUSIONS: The
      results suggest that nicotinic receptor desensitization is responsible for the
      loss of P50 gating in schizophrenia.

PMID- 9646892
TI  - Factor structure and clinical validity of competing models of positive symptoms
      in schizophrenia.
AB  - BACKGROUND: The factor structure of four competing models of positive symptoms
      and their clinical validity was studied in a sample of 253 schizophrenia
      inpatients. METHODS: The following models were tested using confirmatory factor
      analysis: a one-dimension severity model, a two-dimension model comprising a
      psychosis factor and a disorganization factor, a four-dimension model based on
      the Scale for the Assessment of Positive Symptoms (SAPS) structure in subscales,
      and a five-dimension model derived from the previous one by further
      differentiating Schneiderian delusions from non-Schneiderian ones. RESULTS: More
      complex multifactorial models fit the data better than simpler models. The five
      dimension model was the best adjusted (goodness of fit index = .844, nonnormed
      fit index = .812, normed fit index = .728). Whereas the one-dimension model did
      not display significant association with the clinical variables, multidimensional
      models were related to age at onset and illness severity. The two-dimension model
      captured well the clinical correlates of the more complex models. CONCLUSION:
      None of the tested models showed good fit to the data. The one-dimension model
      displayed both poor factor validity and poor external validity; therefore,
      research relying on the SAPS total score may reach misleading conclusions.

PMID- 9646893
TI  - P300 and the thought disorder factor extracted by factor-analytic procedures in
      schizophrenia.
AB  - BACKGROUND: In order to clarify the clinical significance of P300 as a biologic
      marker that can reflect schizophrenic symptomatology, many previous studies have
      evaluated the relationship of P300 with the symptoms on the basis of a
      positive/negative dichotomy, but yielded inconsistent conclusions. Such a
      dichotomy has been criticized as being too reductionistic. Recently, most studies
      with factor-analytic procedures have extracted some symptom factors outside this
      dichotomy. Therefore, it is important to examine associations of P300 with the
      symptom factors extracted by these statistical analyses. METHODS: In the present
      study, the amplitudes of P300 were measured by using an auditory oddball paradigm
      for 73 schizophrenics whose psychopathology was assessed with the Positive and
      Negative Syndrome Scale (PANSS). RESULTS: The principal component analysis of the
      PANSS items revealed five factors labeled the thought disorder, negative,
      hostile/excitable, delusional/hallucinatory, and depressive factors. The score
      for the thought disorder factor correlated negatively with the amplitude of P300
      recorded at Pz T5, and T6, but that for the other factors did not. CONCLUSIONS:
      These findings suggest that the reduction of P300 amplitudes recorded at the
      midline parietal and bilateral temporoparietal regions may be one of the
      electrophysiologic indices representing the thought disorder clinically observed
      in schizophrenia.

PMID- 9646894
TI  - Slow-wave sleep and ventricular size: a comparative study in schizophrenia and
      major depression.
AB  - BACKGROUND: A slow-wave sleep (SWS) deficit and a shortened rapid eye movement
      (REM) sleep latency are commonly described in schizophrenia and depression. In
      addition, a close association between ventricular system measurements and SWS are
      reported in both disorders; however, a comparative, combined polysomnographic and
      computed tomographic investigation is lacking. METHODS: In the present post hoc
      study we analyzed the electroencephalographic sleep pattern and the ventricular
      brain ratio (VBR) of 14 drug-naive schizophrenic patients and of 14 depressed
      patients who were drug-free for a sufficient time period. RESULTS: Whereas the
      depressives showed the often described SWS and REM sleep changes, these
      measurements were quite normal in the schizophrenics. The VBR values were similar
      in both patient groups and exceeded in 71% of the schizophrenics and in 50% of
      the depressives the cutoff point of a "normal" VBR value. A close association
      between SWS and VBR was found in the depressives but not in the schizophrenics.
      CONCLUSIONS: The results of the present study of drug-naive schizophrenic
      patients and of depressed patients indicate only a minor overlap between the
      pathophysiological changes observed in both disorders. Therefore, the present
      investigation adds evidence for the assumption that schizophrenia and depression
      are etiopathogenetically distinct entities, rather than representing points on a
      continuum of liability.

PMID- 9646895
TI  - Electroacupuncture: mechanisms and clinical application.
AB  - Acupuncture is an ancient Chinese method to treat diseases and relieve pain. We
      have conducted a series of studies to examine the mechanisms of this ancient
      method for pain relief. This article reviews some of our major findings. Our
      studies showed that acupuncture produces analgesic effect and that
      electroacupuncture (EA) is more effective than manual acupuncture. Furthermore,
      electrical stimulation via skin patch electrodes is as effective as EA. The
      induction and recovering profiles of acupuncture analgesia suggest the
      involvement of humoral factors. This notion was supported by cross-perfusion
      experiments in which acupuncture-induced analgesic effect was transferred from
      the donor rabbit to the recipient rabbit when the cerebrospinal fluid (CSF) was
      transferred. The prevention of EA-induced analgesia by naloxone and by antiserum
      against endorphins suggests that endorphins are involved. More recent work
      demonstrated the release of endorphins into CSF following EA. In addition, low
      frequency (2 Hz) and high frequency (100 Hz) of EA selectively induces the
      release of enkephalins and dynorphins in both experimental animals and humans.
      Clinical studies suggesting its effectiveness for the treatment of various types
      of pain, depression, anxiety, spinally induced muscle spasm, stroke,
      gastrointestinal disorders, and drug addiction were also discussed.

PMID- 9646896
TI  - Psychotic symptoms and apolipoprotein E genotypes in an elderly population.
AB  - BACKGROUND: Psychotic symptoms have been found to be more common in demented
      elderly persons. Genetic variation in the apolipoprotein E (APOE) gene is
      reported to be associated with variation in the risk of Alzheimer's dementia.
      This study reports on variables associated with psychotic symptoms including
      APOE, in demented and nondemented elderly persons. METHODS: A population of 668
      elderly persons was examined. APOE genotype was available in 309 individuals.
      RESULTS: Psychotic symptoms were found to be associated with dementia, a previous
      psychiatric history, female gender, being less educated, disability in daily
      living and institutionalisation. In the nondemented group, psychotic symptoms
      were equally common in subjects with or without the epsilon 4 present. In the
      demented subjects, psychotic symptoms were slightly more common, although not
      significant, in subjects without the epsilon 4 genotype. CONCLUSIONS: There was
      no statistical significant difference in APOE genotype between subjects with and
      without psychotic symptoms, stratified by dementic diagnosis.

PMID- 9646897
TI  - Schizophrenia and impaired homocysteine metabolism: a possible association.
AB  - BACKGROUND: An increased risk of both schizophrenia and neural tube defects was
      observed in a birth cohort exposed to famine during early gestation. Neural tube
      defects have been related to a folate-sensitive genetic defect in homocysteine
      metabolism. If this were also true for schizophrenia, then cases with low folate
      (LF)--and only these cases--should have increased homocysteine levels compared
      with controls. METHODS: We compared homocysteine levels of schizophrenia cases
      and normal controls with low folate (LF) and without low folate (non-LF). Low
      folate was defined by the bottom tertile for controls. RESULTS: In the LF group
      (6 cases, 8 controls), mean homocysteine was 10.7 microM in cases compared with
      7.7 microM in controls (p = .03). In the non-LF group (11 cases, 16 controls)
      mean homocysteine did not differ for cases and controls. CONCLUSIONS: These pilot
      data are compatible with the hypothesis that a folate-sensitive defect in
      homocysteine metabolism contributes to cases of schizophrenia.

PMID- 9646898
TI  - Analysing the redox status of plant tissues by FSCE.

PMID- 9646899
TI  - Fast narrow-bore HPLC-DAD analysis of biologically active thiosulfinates obtained
      without solvent from wild Allium species.

PMID- 9646900
TI  - Screening of post-explosive samples for common high explosive components by MECC.

PMID- 9646902
TI  - Highly efficient separation of amines by electrokinetic chromatography using
      resorcarene-octacarboxylic acids as pseudo-stationary phases.

PMID- 9646901
TI  - In vivo/in vitro microdialysis coupled to capillary LC-LIF.

PMID- 9646903
TI  - Advantages in the analysis of UDP-sugars by capillary electrophoresis-comparison
      of the conventional HPLC method with two new capillary electrophoretic micro
      procedures.
AB  - Two different capillary electrophoretic separation modes for the analysis of UDP
      sugars have been tested. In comparison to the traditionally used HPLC method the
      micellar electrokinetic capillary chromatography (MECC) as well as the capillary
      zone electrophoresis (CZE) results in an improvement of the separation profile
      and the speed of the analysis.

PMID- 9646904
TI  - Recent applications of polysaccharide-type chiral stationary phases for the
      enantioselective analysis of chiral drugs with one and two stereogenic centers.

PMID- 9646905
TI  - Capillary electrophoresis and capillary chromatography: theoretical analogies and
      practical differences.

PMID- 9646906
TI  - Utilisation of HPLC to substitute preparative column chromatography for the
      quality survey of frying fats and oils.

PMID- 9646907
TI  - Conducting polymer based potentiometric detection applied to the determination of
      organic acids with narrow-bore LC systems.

PMID- 9646908
TI  - Drug analysis by capillary electrophoretic methods.

PMID- 9646909
TI  - Determination of benzalkonium chloride in drug formulations by capillary
      electrophoresis (CE).
AB  - A Capillary Electrophoresis method was developed and applied successfully to test
      the quality of different drug formulations for release and stability studies. In
      the method an uncoated fused-silica capillary was employed containing a
      phosphoric acid buffer electrolyte which was brought to pH by triethylamine. The
      benzalkonium chlorides (BAC-C12 and BAC-C14) present in the standard were
      completely separated from each other and from the peaks of the main compound.
      Performance results of the method in terms of system repeatability, precision and
      accuracy are discussed.

PMID- 9646910
TI  - Enantioseparation of acidic drugs by capillary electrophoresis using dual systems
      with mixtures of charged and neutral cyclodextrins.

PMID- 9646911
TI  - HPTLC assay of cephalexin and cefaclor in pharmaceuticals.
AB  - A simple and reliable HPTLC method for the simultaneous determination of
      cephalexin and cefaclor is developed and validated. The methanol-ethyl acetate
      acetone-water (5:2.5:2.5:1.5 v/v/v/v) solvent system is used for the quantitative
      evaluation of chromatograms. The chromatographic zones, corresponding to the
      spots of cephalexin and cefaclor on the silica gel plates, are scanned in the
      reflectance/absorbance mode at 265 nm. The method is found to be reproducible and
      convenient for the quantitative analysis of cephalexin and cefaclor in its dosage
      forms.

PMID- 9646912
TI  - Capillary electrochromatography (CEC): methodology and applications.

PMID- 9646913
TI  - Determination of aggregates in a formulated recombinant fusion protein by SDS
      capillary electrophoresis.

PMID- 9646914
TI  - Effect of the particle size in capillary electrochromatography.

PMID- 9646915
TI  - Comparison of mass spectrometry interfacing techniques for microcolumn liquid
      separations.

PMID- 9646916
TI  - Evaluation of CZE for studying protein binding of aluminium in human serum.

PMID- 9646917
TI  - Determination of ascorbic acid in nanolitre samples by means of capillary batch
      injection analysis.
AB  - Capillary batch injection analysis (CBIA) is applied to the determination of
      ascorbic acid in nanolitre samples at neutral pH. It is demonstrated that pulsed
      amperometric detection is superior to constant-potential amperometric detection
      with respect to signal stability. The calibration plot is linear within the
      studied concentration range between 0.5 mM and 5 mM and the reproducibility is
      characterized by a relative standard deviation of 0.80% for 10 successive
      injections of 188 nL of 3.5 mM ascorbic acid. The attainable sample throughput is
      up to 500 per hour.

PMID- 9646918
TI  - Application of a new PVC-based ion-selective electrode for surfactant detection
      in microflow systems.

PMID- 9646919
TI  - Separation of tetracycline and its related substances: comparison of liquid
      chromatography, capillary electrophoresis and capillary electrochromatography.

PMID- 9646920
TI  - Comparison of capillary liquid chromatography vs capillary electrophoresis, using
      the same detector.

PMID- 9646921
TI  - High temperature and temperature programming in capillary HPLC.

PMID- 9646922
TI  - Miniaturized thermal lens device for capillary electrophoresis.
AB  - In this paper we will report on the combination of a miniaturized fiber optic
      modified photothermal sensor (size 2 x 2 x 2 cm) to capillary electrophoresis
      (CE) as detection device. The properties and the performances of the thermal lens
      detector, based on a double beam absorption scheme, were studied in a capillary
      electrophoresis system with different types of toxic pollutants, e.g. pesticides.
      A tunable Argon ion laser, which emits between 364 and 514 nm, was adapted to a
      commercial injection and high voltage CE system. The miniaturization of the
      thermal lens detector head with optical waveguides allows the combination with
      typical CE systems, therefore pesticides in microliter volumes can be treated.
      The detector performance is demonstrated with the monitoring of pesticides in
      capillaries with various diameter. The limit of detection is one of two orders of
      magnitude better than conventional absorption detector.

PMID- 9646923
TI  - On-line coupling of capillary HPLC with 1H NMR spectroscopy.

PMID- 9646924
TI  - Narrow-bore liquid chromatography coupled to chemiluminescence detection for the
      analysis of pharmaceutical preparations containing hydrochlorothiazide and
      captopril.

PMID- 9646925
TI  - Flow-injection analysis of hydrochlorothiazide applying sensitised
      chemiluminescence detection: optimisation in view of narrow-bore HPLC.

PMID- 9646926
TI  - Narrow-bore reversed-phase liquid chromatography of metronidazole benzoate and
      its hydrolysis products.

PMID- 9646927
TI  - Comparative narrow-bore high-performance liquid chromatographic determination of
      ketoprofen in horse plasma.

PMID- 9646928
TI  - Narrow-bore HPLC analysis of isoflavonoid aglycones and their O- and C-glycosides
      from Pueraria lobata.

PMID- 9646929
TI  - Trends towards sensitive detection in capillary electrophoresis: an overview of
      some recent developments.

PMID- 9646930
TI  - A first and straightforward approach to detection limits for narrow-bore HPLC and
      CE.
AB  - Two methodologies have been proposed for a simple statistical estimation of the
      detection limits in microbore-HPLC and CE techniques. Due to the impossibility to
      measure the blank, by using the extrapolated or approximated expressions it is
      possible to obtain a straightforward approach of the detection limits from the
      study of the residuals of the calibration data set, avoiding tedious treatment of
      the signals. The utility of these expressions has been checked on the data from
      an experimental microbore HPLC system.

PMID- 9646931
TI  - Chiral separation of antisense oligonucleotides: a feasibility study.

PMID- 9646932
TI  - Advantages of capillary electrophoresis for determination of choline in
      pharmaceutical preparations.
AB  - Assay of choline in pharmaceutical preparations was realized by capillary zone
      electrophoresis (CZE) coupled with indirect UV detection. The suitability of
      several background electrolytes was investigated to optimize the separation of
      choline from other components such as amino acids, betaine and cations. Final
      operating conditions were as follows: a 75 microns x 50 cm uncoated fused-silica
      capillary with an electrolyte consisting of 5 mM creatinine pH 3.2, a voltage of
      25 kV, a temperature of 25 degrees C and an UV detection at 210 nm. Choline
      migrates in less than 5 min and full selectivity vs other analytes was achieved.
      Validation data compared with those obtained with HPLC demonstrated the interest
      of CZE.

PMID- 9646933
TI  - Use of capillary electrophoresis for the characterization of human serum albumin
      heterogeneity.
AB  - Human serum albumin (HSA) is used in large amounts as an excipient in many
      biopharmaceutical formulation to prevent loss of the active ingredient through
      adsorption and/or degradation. Traditionally, iso-electric focusing has been used
      to demonstrate charge heterogeneity in HSA preparations. In an effort to develop
      new methods for the analysis of formulation components, a capillary zone
      electrophoresis method was developed for the analysis of HSA. Under initial
      separation conditions using untreated silica capillaries and 20 mM sodium
      phosphate, pH 6.0 as electrophoretic buffer, HSA migrated as a single peak.
      Addition of 1,4-diaminobutane allowed separation of several components which
      could be further resolved by varying the buffer pH. Optimal separation conditions
      were attained at 5 mM 1,4-diaminobutane and pH 8.5. The reproducibility of the
      separation conditions was verified by using capillaries from a different
      manufacturer. A comparative analysis of HSA preparations from different
      manufacturers provided evidence that the method may be used to qualitatively
      differentiate individual preparations. The analysis of rhEPO formulations,
      composed largely of HSA, showed levels of heterogeneity comparable to that of HSA
      preparations. Electrospray ionisation mass spectrometry (ESA-MS) was used as an
      independent method to confirm the heterogeneous nature of HSA.

PMID- 9646934
TI  - A genetic basis for neuroendocrine-immune interactions.
AB  - Psychoneuroimmunology is an exciting, complex field that elucidates interactions
      among the nervous, endocrine, and immune systems. The contribution of
      psychosocial factors and behavioral processes to these interactions has been the
      focus of numerous studies designed to investigate the intricate pathways that are
      involved in the "mind-body connection." In addition, the effects of this
      connection on the development and progression of various disease conditions are
      of considerable interest. Although efforts have been made to identify the
      cellular and molecular mechanisms underlying these relationships, the impact of
      genetic makeup on the communication among these systems has yet to be fully
      realized. The development of sophisticated genetic analytical methods and gene
      mapping techniques now provide the "tools" to determine the influence of genetics
      on behavior-neuroendocrine-immune interactions--an area of study that may
      represent the next frontier in psychoneuroimmunology.

PMID- 9646935
TI  - Attenuation of behavioral abnormalities in autoimmune mice by chronic soluble
      interferon-gamma receptor treatment.
AB  - NZB x NZW F1 hybrid (B/W) mice develop altered behavior in the elevated plus maze
      and novel object tasks between 6 and 12 weeks of age in parallel with lupus-like
      autoimmune disease. To confirm the relationship between disease progression and
      development of behavioral abnormalities, B/W and nonautoimmune NZW mice received
      chronic treatment with a soluble IFN gamma receptor (sIFN gamma R), a treatment
      known to retard autoimmune disease progression, or vehicle, beginning at 6 weeks
      of age. After 6 weeks of treatment, elevated plus maze and novel object testing
      revealed that although sIFN gamma R treated B/W mice still differed from NZW
      mice, chronic sIFN gamma R treatment significantly retarded the development of
      behavioral abnormalities in the B/W mice, while the NZW mice were not affected by
      this treatment. sIFN gamma R treated B/W mice were more active in both the plus
      maze and novel object tasks, and displayed less plus maze anxiety behavior and
      more exploratory activity in the novel object task compared to vehicle treated
      B/W mice. To clarify the role of acute action of the sIFN gamma R on the elevated
      IFN gamma levels of B/W mice, a second experiment examined the effects of a
      single injection of sIFN gamma R on B/W and NZW mice. Unlike chronic treatment,
      acute treatment with the same dose of sIFN gamma R did not affect plus maze or
      novel object behavior in 12-week-old mice. These results add to the growing
      evidence that lupus-associated behavioral abnormalities are a direct effect of
      the autoimmune disease.

PMID- 9646936
TI  - Localization of corticotropin-releasing factor in primary and secondary lymphoid
      organs of the rat.
AB  - Cells of the immune system produce a variety of neuropeptides or peptide
      hormones, either constitutively or upon induction, and possess specific
      neuropeptide receptors that display ligand-receptor interactions similar to those
      described in the central nervous system (CNS). These findings suggest that
      specific subsets of lymphoid cells can produce and respond to peptides previously
      thought to be principally neural mediators. Recently, corticotropin releasing
      factor (CRF) mRNA was detected in the rat thymus and spleen, although the cells
      that synthesize CRF were not identified. We examined the localization of CRF and
      its mRNA in the rat spleen, thymus, and mesenteric lymph nodes using
      immunocytochemistry (ICC) and in situ hybridization (ISH), respectively.
      Immunoreactive CRF was present in cells in the marginal zone and red pulp of the
      spleen, in connective tissue septa and the subcapsular region of the thymus, and
      in the medullary cords and sinuses of the mesenteric lymph nodes. Dual ICC/ISH
      for CRF and its mRNA, respectively, demonstrated CRF mRNA over CRF-immunoreactive
      cells, suggesting CRF synthesis. Double-label ICC for CRF and markers for
      specific immunocyte subsets suggest that CRF+ cells in the spleen and thymus are
      macrophages. CRF+ cells in primary and secondary lymphoid organs reside in
      compartments that are innervated by sympathetic nerves, and some cells appears to
      be contacted by noradrenergic sympathetic nerve fibers, suggesting that CRF
      release may be influenced by the sympathetic nervous system, as it is in the
      hypothalamo-pituitary-adrenal axis. The presence of CRF in organs of the immune
      system suggests that this neuropeptide may modulate immune functions after
      paracrine release.

PMID- 9646937
TI  - Increased number of mast cells in the central nervous system of adult male mice
      following chronic subordination stress.
AB  - Mast cells (MCs) are amine-storing cells with heterogeneous histological,
      biochemical, and functional properties. They are found in connective tissue as
      well as in the peripheral and central nervous system (CNS) of many mammalian
      species. In this study we investigated whether the distribution of MCs in the CNS
      of adult male CD-1 mice was modified following repeated defeat stress.
      Experimental subjects underwent a 3-week period of fighting encounters with a
      highly aggressive resident. On the test day they were divided into three groups:
      (a) paired with the resident for 20 min; (b) placed in a cage containing the
      soiled bedding of the resident for 20 min; (c) placed in a cage with clean
      sawdust for 20 min. Results show that previous defeat stress increases the number
      of MCs in the thalamus, habenula, and hypothalamus of subjects exposed to a
      fighting opponent or to a clean cage, compared to subjects placed in a cage with
      the bedding of the opponent or to a group-housed, nondefeated control. These
      results, together with previous reports in birds and rodents, suggest that MCs
      have a wider role than previously expected and might be involved in the
      behavioral response to highly relevant psychosocial stimuli.

PMID- 9646938
TI  - Chronic varied stress modulates experimental autoimmune encephalomyelitis in
      Wistar rats.
AB  - Stress disturbs homeostasis by altering the equilibrium of various hormones which
      have a significant impact on immune responses. Few studies have examined the
      influence of stressors on autoimmune disease in animal models. In our work, we
      studied the effects of long-term exposure (14 days) to chronic varied stress
      (CVS) in a model of experimental autoimmune encephalomyelitis (EAE) in Wistar
      rats. We studied whether the exposure to CVS before or after the immune challenge
      would correlate with differences in the clinical course of the disease. We also
      examined whether the CVS would modulate the magnitude of the cellular or the
      humoral immune response. We observed opposite effects on the clinical signs in
      animals stressed before or after the immune challenge. The clinical signs of the
      disease were attenuated in animals stressed before but not after the immune
      challenge. Relationships were found in the modulation of the clinical severity
      related to the time of exposure to the CVS, the histological alterations and the
      proliferative results. Stressed animals with milder clinical signs presented an
      exacerbated humoral response against myelin antigens while stressed animals with
      more severe clinical symptoms exhibited a significantly diminished one. Besides,
      we detected the presence of specific IgG1 associated with the exposure to CVS
      before the induction of EAE. Our results show that, depending on the timing of
      the exposure of Wistar rats to the CVS, the neuroendocrine disbalance favors a
      more pronounced humoral or cellular profile of the response.

PMID- 9646939
TI  - Differential effects of NMDA-induced lesions into the insular cortex and amygdala
      on the acquisition and evocation of conditioned immunosuppression.
AB  - It has been established that the insular cortex (IC) mediates conditioned taste
      aversion, and recently we have demonstrated that lesions of this structure
      disrupt the acquisition of conditioned immunosuppression (CIS). The IC is
      functionally and reciprocally interconnected with the amygdala (AM) which has
      been suggested to be involved in neural-immune interactions. The aim of this work
      was to test the effects of NMDA-induced lesions in either the IC or AM in the
      acquisition (lesions made before conditioning) and evocation (lesions made after
      conditioning) of a conditioned immunosuppression task, obtained by one single
      pairing of saccharin taste and the immunosuppressive drug, cyclophosphamide. AM
      and IC lesioned rats were separated into four groups: the first two received
      lesions before and the other two were lesioned after the acquisition of
      conditioned immunosuppression. Twenty days after conditioning, animals were
      reexposed to saccharin and immunized with ovalbumin. After immunization, blood
      samples were taken, and analyzed by ELISA. The results showed that IC lesions
      disrupted the acquisition and evocation of CTA and CIS. Conversely, AM lesions
      disrupted only the acquisition of CIS. These data suggest that the IC is involved
      in the neural mechanisms underlying the acquisition and evocation of conditioned
      immunosuppression, and the amygdala could be important in mediating the input of
      the immune information necessary for the acquisition of conditioned
      immunosuppression.

PMID- 9646940
TI  - Functional homodimeric glycoprotein hormones: implications for hormone action and
      evolution.
AB  - BACKGROUND: Human chorionic gonadotropin (hCG), lutropin, follitropin, and
      thyrotropin act as alpha beta heterodimers to control reproduction and thyroid
      function. The alpha and beta subunits of these proteins are divided into three
      loops (alpha 1,alpha 2,alpha 3; beta 1,beta 2,beta 3) by cysteine knots and the
      heterodimer is stabilized by 20 beta-subunit residues wrapped around alpha 2 like
      a seatbelt. Understanding how these hormones interact with their receptors, a
      matter of considerable dispute, would facilitate design of pro- and anti
      fertility agents. RESULTS: By swapping alpha 2 for beta 2 and vice versa and, in
      some cases, adding an amino-terminal coiled-coil dimerization domain, we prepared
      homodimeric analogs that have the conformation found in each 'half' of hCG.
      Homodimers containing loops beta 1,alpha 2,beta 3 and none, part, or all of the
      seatbelt stimulated signal transduction to the same extent as hCG, albeit with
      lower potency. Those containing alpha 1,beta 2,alpha 3 were inactive.
      CONCLUSIONS: The activities of homodimers containing the beta 1,alpha 2,beta 3
      groove exceed those of other minimized analogs more than 100-1000-fold,
      suggesting this portion of the hormone forms the major receptor contact. The
      discovery that glycoprotein hormone heterodimers can be converted to functional
      homodimers supports the proposal that this protein family evolved from an active
      homodimeric ancestor by gene duplication and acquisition of mutations to loop 2
      that prevent homodimerization. This approach to protein minimization should be
      applicable to other proteins composed of architecturally related subunits,
      including those that might have arisen by gene duplication.

PMID- 9646941
TI  - Synergistic activation of soluble guanylate cyclase by YC-1 and carbon monoxide:
      implications for the role of cleavage of the iron-histidine bond during
      activation by nitric oxide.
AB  - BACKGROUND: Nitric oxide (.NO) is used in biology as both an intercellular
      signaling agent and a cytotoxic agent. In signaling, submicromolar quantities of
      .NO stimulate the soluble isoform of guanylate cyclase (sGC) in the receptor
      cell. .NO increases the Vmax of this heterodimeric hemoprotein up to 400-fold by
      interacting with the heme moiety of sGC to form a 5-coordinate complex. Carbon
      monoxide (CO) binds to the heme to form a 6-coordinate complex, but only
      activates the enzyme 5-fold, YC-1 is a recently discovered compound that relaxes
      vascular smooth muscle by stimulating sGC. RESULTS: In the presence of YC-1, CO
      activates sGC to the same specific activity as attained with .NO. YC-1 did not
      affect the NO-stimulated activity. The on-rate (kon) and off-rate (koff) of CO
      for binding to sGC in the presence of YC-1 were determined by stopped-flow
      spectrophotometry. Neither the kon nor the koff varied from values previously
      obtained in the absence of YC-1, indicating that YC-1 has no effect on the
      affinity of CO for the heme. In the presence of YC-1, the visible spectrum of the
      sGC-CO complex has a Soret peak at 423 nm, indicating the complex is 6
      coordinate. CONCLUSIONS: YC-1 has no effect on the affinity of CO for the heme of
      sGC. In the presence of YC-1, maximal activation of sGC by CO is achieved by
      formation of a 6-coordinate complex between CO and the heme indicating that
      cleavage of the Fe-His bond is not required for maximal activation of sGC.

PMID- 9646942
TI  - DNA damage induced via independent generation of the radical resulting from
      formal hydrogen atom abstraction from the C1'-position of a nucleotide.
AB  - BACKGROUND: Deoxyribonucleotide radicals resulting from formal C1'-hydrogen atom
      abstraction are important reactive intermediates in a variety of DNA-damage
      processes. The reactivity of these radicals can be affected by the agents that
      generate them and the environment in which they are produced. As an initial step
      in determining the factors that control the reactivity of these important radical
      species, we developed a mild method for their generation at a defined site within
      a biopolymer. RESULTS: Irradiation of oligonucleotides containing a photolabile
      nucleotide produced C1'-DNA radicals. In the absence of potential reactants other
      than O2, approximately 90% of the damage events involve formation of alkaline
      labile lesions, with the remainder resulting in direct strand breaks. The ratio
      of alkaline-labile lesions to direct strand breaks (approximately 9:1) is
      independent of whether the radical is generated in single-stranded DNA or double
      stranded DNA. Strand damage is almost completely quenched under anaerobic
      conditions in the presence of low thiol concentrations. Competition studies with
      O2 indicate that the trapping rate of C1'-DNA radicals by beta-mercaptoethanol is
      approximately 1.1 x 10(7) M-1s-1. CONCLUSIONS: The mild generation of the C1'-DNA
      radical in the absence of exogenous oxidants makes it possible to examine their
      intrinsic reactivity. In the absence of other reactants, the formation of direct
      strand breaks from C1'-radicals is, at most, a minor pathway. Competition studies
      between beta-mercaptoethanol and O2 indicate that significantly higher thiol
      concentrations than those in vivo or some means of increasing the effective thiol
      concentration near DNA are needed for these reagents to prevent the formation of
      DNA lesions arising from the C1'-radical under aerobic conditions.

PMID- 9646943
TI  - Nitrite and nitrate analyses: a clinical biochemistry perspective.
AB  - OBJECTIVE: To review the assays available for measurement of nitrite and nitrate
      ions in body fluids and their clinical applications. DESIGN AND METHODS:
      Literature searches were done of Medline and Current Contents to November 1997.
      RESULTS: The influence of dietary nitrite and nitrate on the concentrations of
      these ions in various body fluids is reviewed. An overview is presented of the
      metabolism of nitric oxide (which is converted to nitrite and nitrate). Methods
      for measurement of the ions are reviewed. Reference values are summarized and the
      changes reported in various clinical conditions. These include: infection,
      gastroenterological conditions, hypertension, renal and cardiac disease,
      inflammatory diseases, transplant rejection, diseases of the central nervous
      system, and others. Possible effects of environmental nitrite and nitrate on
      disease incidence are reviewed. CONCLUSIONS: Most studies of changes in human
      disease have been descriptive. Diagnostic utility is limited because the
      concentrations in a significant proportion of affected individuals overlap with
      those in controls. Changes in concentration may also be caused by diet, outside
      the clinical investigational setting. The role of nitrite and nitrate assays
      (alongside direct measurements of nitric oxide in breath) may be restricted to
      the monitoring of disease progression, or response to therapy in individual
      patients or subgroups. Associations between disease incidence and drinking water
      nitrate content are controversial (except for methemoglobinemia in infants).

PMID- 9646944
TI  - The place of electron spin resonance methods in the detection of oxidative stress
      in type 2 diabetes with poor glycemic control.
AB  - OBJECTIVE: Chronic production of reactive oxygen species (ROS) and/or deficiency
      in the antioxidant defense system are observed in non-insulin-dependent diabetes
      mellitus (NIDDM) patients. As an adjunct to the usual indirect parameters for
      evaluating oxidative stress, we assessed the feasibility of oxyradicals detection
      in venous blood by electron spin resonance spectroscopy (ESR). Detection of the
      ascorbate pool was also performed using the validated ESR analysis of the
      ascorbyl free radial (AFR)-dimethyl sulfoxide (DMSO) complex. METHODS AND
      RESULTS: Plasma lipoperoxidation was characterized by higher levels of total MDA
      (1.50 +/- 0.08 nmol/L), lower levels of GSH (0.54 +/- 0.02 mmol/L) and of vitamin
      A (2.13 +/- 0.52 mumol/L) in the NIDDM group than in the controls (0.75 +/- 0.05
      nmol/L, 0.90 +/- 0.05 mmol/L, 3.52 +/- 1.04 mumol/L, respectively). Improvement
      of the ESR measurement of oxyradical adducts has been previously obtained by
      addition of a new sensitive nitrone (DEPMPO), which acts as a spin-trap. However,
      in our experiment the ESR signal-to-noise ratio was too low to detect
      significative oxyradicals adducts in total venous blood of NIDDM patients having
      a weak production of ROS. A significant difference (p < 0.002) was observed in
      DMSO/AFR index between controls (24.00 +/- 4.10 nmol/L) and NIDDM patients (7.28
      +/- 2.36 nmol/L) suggesting ascorbate depletion related to the free radical
      production. CONCLUSION: The DMSO/AFR index could be an interesting additional
      marker of oxidative stress during a chronic production of ROS.

PMID- 9646945
TI  - Interference of 6 beta-hydroxycortisol in the quantitation of urinary free
      cortisol by immunoassay and its elimination by solid phase extraction.
AB  - OBJECTIVE: To study the cross-reactivity of 6 beta-hydroxycortisol (6 beta-OHF)
      with anticortisol antibodies and subsequent interference with urinary free
      cortisol (UFC) quantitation in commercial immunoassay kits. A solid-phase
      extraction (SPE) technique was evaluated for removal of 6 beta-OHF from the
      specimen. METHODS: Interference by 6 beta-OHF was studied in three enzyme
      immunoassay and three radioimmunoassay kits. Interference was assessed by the
      multiple regression equation derived from a 4 x 4 matrix composed of four levels
      of cortisol and four levels of 6 beta-OHF. Sep-Pak Plus C18 cartridges were used
      to remove 6 beta-OHF from the specimens, and optimum conditions for fractionating
      6 beta-OHF from cortisol were determined by eluting the cartridge with a stepwise
      increment in methanol concentration. HPLC was used to monitor cortisol and 6 beta
      OHF in the sample and cartridge eluates. RESULTS: Cross-reactivity of 6 beta-OHF
      with anticortisol antibodies was variable and depended on the cortisol kit used
      with a range from 0.1 to 10%. Multiple regression analysis indicated that 6 beta
      OHF interfered positively with the cortisol assay regardless of cortisol
      concentrations. Extraction of UFC by methylene chloride as recommended by some
      immunoassay kits yielded a significant constant error to the UFC results which
      was nearly proportional to the added levels of 6 beta-OHF. SPE of samples
      completely removed 6 beta-OHF from the specimen when a 40% methanol elution step
      was included. Consequently, specimens processed in this manner did not show
      interference in UFC measurements even in samples spiked with 2.38 mumol/L of 6
      beta-OHF. CONCLUSIONS: Elevated urinary 6 beta-OHF may be a significant source of
      interference in UFC immunoassays. SPE of samples prior to analysis would be a
      simple and inexpensive means for removing 6 beta-OHF from urine specimens,
      therefore, increasing accuracy and precision in UFC measurements by immunoassay.

PMID- 9646946
TI  - Myocardial ischemic injury and purine metabolism in patients undergoing coronary
      artery bypass.
AB  - OBJECTIVES: High-energy phosphates and their catabolic products were determined
      in myocardium during coronary artery bypass surgery with blood cardioplegic
      reperfusion in order to evaluate the effects of aortic cross-clamping and
      reoxygenation on myocardial purine metabolism. DESIGN AND METHODS: Transmural
      left ventricular biopsy specimens were taken with ITu-Cut biopsy needles, before
      aortic cross-clamping, before cross-clamp removal and after 30' of reperfusion;
      perchloric extracts of the material were analyzed for nucleotide content by
      capillary zone electrophoresis (CZE). The CZE procedure used separates the
      complete spectrum of purine metabolites in myocardial extracts obtained from 0.6
      8.6 mg biopsy material. RESULTS: The basal values of ATP/ADP ratio and energy
      charge were low, IMP content was high. After the ischemic period, ATP levels
      further decreased and IMP, nucleosides and bases accumulated. After reperfusion,
      nucleoside and base basal levels, but not energy charge, were restored to some
      extent. CONCLUSIONS: The study arises the problem of myocardial preservation
      during heart surgery. In this investigation, capillary electrophoresis was an
      extremely adaptable technique for the evaluation of ischemic injury and could be
      useful in studying the effects of cardioplegic solutions.

PMID- 9646947
TI  - Accelerated linear growth and advanced bone age in Sotos syndrome is not
      associated with abnormalities of collagen metabolism.
AB  - OBJECTIVES: To investigate whether the advanced bone age in Sotos syndrome is
      associated with alterations in type I collagen metabolism in bone. DESIGN AND
      METHODS: The metabolism of collagen was studied by analyzing the production, gene
      expression and degradation of type I collagen in dermal fibroblast strains from
      patients with Sotos syndrome and comparing them with fibroblasts from age-matched
      healthy subjects. Collagen production was determined as collagenase digestible
      radioactivity and collagen mRNA levels were measured by RT-PCR. Collagen
      degradation was assessed by specific collagenase assay and gelatin zymography. To
      determine the structural defects in type I collagen, the newly synthesized
      proteins were analyzed by SDS-PAGE before and after proteolytic digestion with
      pepsin. RESULTS: In the present study, we have demonstrated that the collagen
      production, secretion and degradation in Sotos syndrome is comparable to
      controls. In addition, no qualitative differences in mRNA transcripts for type I
      collagen were detected between the control and Sotos syndrome fibroblasts. The
      secretion and intracellular accumulation of procollagen is also comparable to
      controls. The analysis of both procollagen and collagen on SDS-PAGE did not
      exhibit any major structural changes as compared with controls. CONCLUSIONS: Our
      results on several aspects of collagen metabolism have demonstrated for the first
      time that collagen, the most abundant of mammalian proteins and the major
      constituent of bone, is normal in patients with Sotos syndrome. Therefore, it
      appears that the advanced bone age and accelerated linear growth seen in patients
      with Sotos syndrome may not be attributed to inherent abnormalities of collagen
      metabolism. The etiology and the pathogenesis of Sotos syndrome still remains
      unclear.

PMID- 9646948
TI  - A prospective longitudinal study of platelet angiotensin II receptors for the
      prediction of preeclampsia.
AB  - OBJECTIVES: We developed a simplified method using a relatively small volume of
      blood for the determination of platelet angiotensin II receptors by saturation
      analysis and we evaluated its performance for the prediction of preeclampsia.
      DESIGN AND METHODS: A platelet suspension with minimal contamination by
      leukocytes and erythrocytes is obtained by centrifugation and washing. The
      platelet concentrate is incubated in a multi-well plate with increasing
      concentration of radiolabelled angiotensin II in the presence or absence of an
      excess of unlabelled angiotensin II. Bound and free fractions are separated using
      an oil mixture. Maximum binding is determined by Scatchard plot. This method was
      compared with a previously reported method. Our method was prospectively
      evaluated in 801 women attending our institution for routine prenatal care. A
      specimen was obtained at each trimester of pregnancy whenever possible. Diagnosis
      of preeclampsia was done postnatally by an experienced obstetrician. RESULTS: The
      method showed acceptable correlation with a previously published method although
      a proportional bias of 2.1 was observed between the two methods. No differences
      in mean maximum binding were observed between normal and affected pregnancies at
      either trimester. Even when the results were analyzed longitudinally, using the
      change in maximum binding between two trimesters for each patient, no significant
      increase could be documented in preeclamptic pregnancies. CONCLUSIONS: Platelet
      angiotensin II receptor measurement is not a clinically useful marker for the
      prediction of preeclampsia.

PMID- 9646949
TI  - Baseline diene conjugation in LDL lipids as a direct measure of in vivo LDL
      oxidation.
AB  - OBJECTIVES: To additionally test validity of the recently developed method (LDL
      baseline diene conjugation, LDL-BDC) for determination of circulating oxidized
      LDL. DESIGN AND METHODS: A detailed comparison between the ultracentrifugation
      and heparin precipitation methods for LDL isolation was performed to test
      suitability of the fast precipitation method. Validity of LDL-BDC as an indicator
      of circulating oxidized LDL was tested by comparing LDL-BDC to results obtained
      by the immunological autoantibody method. RESULTS: BDC values in LDL isolated by
      heparin precipitation did not differ from those isolated by sequential
      ultracentrifugation. While highest amount of diene conjugation was found in LDL
      (40% of that in serum), substantial amounts were also found in VLDL (31%) and HDL
      (25%). When analyzed in the same samples, assays for the titer of autoantibodies
      against oxidized LDL and LDL-BDC were found to show good correlation (r = 0.57, p
      = 0.001, n = 29). CONCLUSIONS: These results, together with thus far conducted
      studies on clinical applicability of the method, indicate that LDL-BDC is a
      promising candidate in search for a method for estimation of LDL oxidation in
      vivo.

PMID- 9646950
TI  - A survey to identify potential outcome indicators for a hospital blood glucose
      monitoring program.
AB  - OBJECTIVE: A survey of operators of a bedside blood glucose monitoring (BGM)
      program at a tertiary health care institution was performed to identify potential
      outcome indicators for our quality assurance program. DESIGN AND METHODS: 170
      surveys were randomly distributed to each nursing unit. The survey consisted of
      20 questions on 4 pages. At the time of the survey, the BGM program consisted of
      514 operators and 33 blood glucose meters on 17 inpatient nursing units servicing
      a total of 445 hospital beds. RESULTS: Seventy-eight percent of surveys were
      returned. Seventy-one percent of operators used the glucose meter at least once a
      week, 17% used it less than once a week, and 12% used it less than once a month.
      When asked how often they thought operators should perform BGM to ensure
      reliability, 65% stated "at least monthly," 8% said "bimonthly," and 27% said "3
      to 4 times a year." In the previous 3 months, 59% of operators recalled "never
      having to repeat a BGM measurement with the glucose meter." 56% recalled "never
      having to confirm a BGM result by sending a venous sample to the central
      laboratory," 38% recalled "sending a venous sample once or twice;" 4% recalled
      "three or four times;" and 2% recalled "more than four times." Fifty-two percent
      recalled having to perform a stat analysis "less than once per month," 37%
      recalled "once or twice per month," and 11% recalled "once or twice per week."
      CONCLUSIONS: Through this survey we obtained information from our operators about
      the current functioning of our BGM program. Based on this information, we were
      able to develop a list of potential outcome indicators that we encourage health
      care institutions with BGM programs to consider incorporating in their quality
      assurance (QA) program.

PMID- 9646951
TI  - 5'-nucleotidase activity in lymphocytes from patients affected by B-cell chronic
      lymphocytic leukemia.
AB  - OBJECTIVES: The activity of membrane-bound ecto-5'-nucleotidase and soluble e-Ns
      and c-N-II 5'-nucleotidases was evaluated on lymphocytes from patients affected
      by B-cell chronic lymphocytic leukemia (B-CLL). A statistically significative
      decrease in ecto-5'-nucleotidase, e-Ns, and c-N-II activities was observed in
      peripheral blood lymphocytes and in B and T populations from affected
      individuals. DESIGN AND METHODS: For the assay of ecto-5'-nucleotidase, e-Ns, and
      c-N-II activity we used a radioactive procedure coupled to HPLC. Since the ecto
      5'-nucleotidase is identified as CD73 antigen, we performed immunofluorescence
      analysis using a specific monoclonal antibody. We analyzed ecto-5'-nucleotidase
      mRNA by RT-PCR to ascertain the possibility of an alteration in the transcription
      of its gene. RESULTS: A decrease in ecto-5'-nucleotidase activity was correlated
      to reduction in ecto-5'-nucleotidase positive cells (CD73+) in leukemia patients.
      RT-PCR produced a fragment of the expected size and the specific mRNA was found
      expressed in both healthy subjects and leukemia patients. CONCLUSIONS: The
      decrease in ecto-5'-nucleotidase activity in patients with B-CLL is not due to
      loss of transcription of the specific mRNA. The presence of point mutations,
      splicing alteration, or posttranslational modifications must be investigated. If
      a defect at DNA or RNA level will be detected, the molecular analysis will be
      considered for diagnosis of B-cell chronic lymphocytic leukemia.

PMID- 9646952
TI  - Stability of digoxin and digitoxin in specimens collected in blood collection
      tubes containing serum separator gels.

PMID- 9646953
TI  - Lipoperoxides kit evaluated for measuring lipoperoxides in biological samples:
      reference intervals for human plasma.

PMID- 9646954
TI  - Lack of association between apolipoprotein H polymorphism and plasma lipid levels
      in Koreans.

PMID- 9646955
TI  - Prostate specific antigen production by breast tumors after induction with oral
      contraceptives.

PMID- 9646956
TI  - Observational studies.
AB  - Observational studies are important methodologies to evaluate exposures and risk
      factors that are not amenable to experimental trials. They offer the advantage of
      being more generalizable to our patients, as these studies may have more liberal
      inclusion criteria than the typical randomized trial. Their disadvantage is their
      susceptibility to biases and their inability to control for unknown factors that
      may impact on the outcome of interest. Establishing causality of an association
      noted in observational studies is an intricate process that requires careful
      assessment. Clinicians and researchers should be familiar with observational
      studies so they may better evaluate a proposed causal relationship and the
      quality of reports claiming such relationships. Only then can they determine if
      the findings are valid and applicable to their patient population.

PMID- 9646957
TI  - Randomized controlled trials.

PMID- 9646958
TI  - Power and sample size.

PMID- 9646959
TI  - Screening and diagnostic testing.

PMID- 9646960
TI  - Meta-analysis for the practicing obstetrician-gynecologist.

PMID- 9646961
TI  - Decision analysis.

PMID- 9646962
TI  - Cost analysis in obstetrics and gynecology.

PMID- 9646963
TI  - Interpretation of the literature.
AB  - To remain clinically competent, you must read! Continued clinical effectiveness
      is learning how to decide when your current diagnostic and management maneuvers
      are no longer good enough and need to be changed! The evidence for obstetric and
      gynecologic practice is growing exponentially (it is about time!) and it is time
      that we, the clinicians, offer our patients the benefits of incorporating that
      evidence into practice. Interpretation of the literature is one step along the
      way to the evaluation and practice of evidence-based medicine!

PMID- 9646964
TI  - The Cochrane Collaboration: evaluation of health care and services using
      systematic reviews of the results of randomized controlled trials.

PMID- 9646965
TI  - The U.S. Preventive Services Task Force: putting evidence-based medicine to work.
AB  - The U.S. Preventive Services Task Force is a prominent example of evidence-based
      medicine put to work. The Guide to Clinical Preventive Services and its Canadian
      counterpart distill thousands of articles into easily understood guidelines for
      the busy clinician. Rather than dictating practice, it provides the scientific
      base for prevention services. The second fundamental part of evidence-based
      medicine is the filtering of that evidence through the clinical skill of the
      clinician. Only the clinician can judge the applicability of the evidence and the
      preferences of the woman and her family. Some common preventive practices in
      women's health lack a scientific basis. Others clearly work. To maximize benefit,
      clinicians should emphasize and encourage prevention strategies that are
      effective. These include cervical cytology screening, blood pressure screening,
      urine cultures in early pregnancy, testing for phenylketonuria, and discouraging
      smoking. No health program can be reviewed in a vacuum. This is especially true
      in the managed care era. Clinicians must ask what benefit would have accrued had
      the same amount of time and money been spent on alternative programs. If
      practices with only a class C recommendation draw money and resources from other
      programs of proven worth (e.g., class A recommendations), then the former have a
      net negative impact on women's health. The Task Force report helps women,
      clinicians, payers, and policymakers make these important decisions.

PMID- 9646966
TI  - Practice guidelines--a continuing debate.

PMID- 9646967
TI  - Evidence-based healthcare quality management in obstetrics and gynecology.

PMID- 9646968
TI  - Intrapartum electronic fetal monitoring: data for clinical decisions.

PMID- 9646969
TI  - Vaginal birth after cesarean.
AB  - Vaginal birth or trial of labor after previous cesarean delivery represents one
      of the most significant changes in obstetric practice. There are numerous reasons
      that influence the decision to proceed with either a trial of labor after
      previous cesarean delivery or elective repeat cesarean delivery. For the majority
      of women with a previous cesarean delivery, a trial of labor should be
      encouraged. There are few absolute contraindications. Women with a previous
      classical uterine incision should not undergo a trial of labor and should be
      delivered once fetal lung maturity is documented. An attempted trial of labor
      should not be discouraged in women with a previous low vertical uterine incision,
      although the patient should be counseled that the evidence as to the risks and
      benefits of a trial of labor is limited. In those situations where the previous
      uterine incision is unknown, but suggestive of a classical uterine incision, an
      argument can be made for elective repeat cesarean delivery once fetal lung
      maturity is documented. When the history of a uterine incision is unknown and
      unlikely to be classical, a trial of labor can be attempted after counseling.
      Close intrapartum management is warranted in this situation. The optimal
      management of labor in women with a previous low transverse uterine incision who
      desire a trial of labor with a breech presentation, multiple gestation, orin whom
      induction of labor is necessary is uncertain; the evidence as to the risks and
      benefits of a trial of labor is limited and obstetric management should be
      individualized after counseling. Uterine rupture represents the most catastrophic
      complication of a trial of labor after previous cesarean delivery. In women
      suspected of having a uterine scar injury, prompt intervention is necessary to
      minimize both maternal and neonatal complications. Women who are not successful
      with a trial of labor require repeat cesarean delivery and appear to be at
      greatest risk for maternal complications. Identifying those women most likely to
      be successful with an attempted trial of labor after previous cesarean while also
      incurring the least maternal and perinatal morbidity and mortality would be
      ideal. At present, however, there is no sufficiently predictive method to
      identify those women most likely to benefit from an elective repeat cesarean
      delivery. The management of labor in women with a previous uterine scar is not
      low risk. As the number of women who attempt vaginal birth after previous
      cesarean delivery increases, we should focus on trying to develop reliable
      methods of identifying women who should and should not undertake a trial of labor
      after cesarean delivery.

PMID- 9646970
TI  - Medical management of ectopic pregnancy.
AB  - In selected patients who are hemodynamically stable with an unruptured tubal
      pregnancy, systemic methotrexate has success rates comparable to laparoscopic
      salpingostomy. Larger randomized studies are necessary to adequately assess
      subsequent fertility. Local injection of methotrexate or other agents requires a
      sonographically visible ectopic as well as technical skills, and has less
      consistent success rates than that of systemic MTX therapy.

PMID- 9646971
TI  - Treatment of endometriosis.

PMID- 9646972
TI  - Prophylactic cesarean for prenatally diagnosed malformations.

PMID- 9646973
TI  - Premenstrual syndrome therapy.

PMID- 9646974
TI  - Evidence-based management of chronic pelvic pain.
AB  - Diagnosis and management of chronic pelvic pain are greatly facilitated by a
      multidisciplinary approach integrating medical intervention with identification
      and management of socioenvironmental problems, cognitive-behavioral pain
      strategies, and treatment of concurrent psychological morbidity. Available
      evidence suggests that outcomes, including pain severity, general health and
      functional status, and disability are more significantly improved after this
      approach than after isolated medical or surgical interventions. Because of the
      chronic nature of many of the underlying psychological and social factors
      predisposing to chronic symptom formation and maintenance, care of the patient
      with chronic pelvic pain must be continuous and longitudinal if recurrent adverse
      sequelae, including disability, inappropriate healthcare utilization, and
      recurrent depression, are to be prevented.

PMID- 9646975
TI  - Management of idiopathic thrombocytopenic purpura in pregnancy.

PMID- 9646976
TI  - Epidural analgesia for labor: effect on the cesarean birth rate.

PMID- 9646977
TI  - Antibiotic therapy for preterm premature rupture of membranes.
AB  - Antibiotic treatment of the patient with preterm premature rupture of membranes
      remote from term significantly prolongs pregnancy and reduces amnionitis without
      increasing the risk of cesarean delivery. Antibiotic treatment reduces perinatal
      infectious morbidity including neonatal sepsis, GBS sepsis, and pneumonia.
      Stratified analysis of the currently available prospective trials also
      demonstrates a significant reduction in gestational-dependent morbidity,
      specifically respiratory distress and intraventricular hemorrhage with treatment.
      This is supported by a reduction in composite infant morbidity and other
      gestational age-dependent morbidities in the NICHD-MFMU trial. Although the
      optimal treatment regimen has not been determined, limited duration broad
      spectrum antibiotic treatment is justified in the setting of conservative
      management of pPROM remote from term. The patient with pPROM and documented
      pulmonary maturity near term may benefit more from expeditious delivery than from
      expectant management with antibiotics.

PMID- 9646978
TI  - Anatomy of the pleura.
AB  - The lung and heart, the vital organs, have to be protected and also have to move
      and change volume continuously to function. For the best protection and function
      of the lung, the thorax is shaped almost like a bellows with the diaphragm as the
      moving part. Furthermore, the outer surface of the lung and the inner surface of
      the protective thoracic cage are covered by an elastic, serous, and lubricating
      membrane to form the pleural cavity. This is almost like inserting a sealed-wet
      and stretchable-plastic bag between the lung and the thoracic wall and diaphragm
      to decrease friction. The lubrication is accomplished by the facing mesothelial
      cells that have bushy-surface microvilli enmeshing hyaluronic acid-rich
      glycoproteins. The amount of fluid in the pleural cavity is regulated by the
      hydrostatic-osmotic pressure relationship and pleuro-lymphatic drainage. Excess
      fluid, large particles, and cells in the pleural cavity are removed through
      preformed stomas assisted by respiratory movements. The stoma is found only in
      the anterior lower thoracic wall and diaphragm and is like the drain of a sink.
      Finally, clinical and subclinical injuries of the pleura appear to occur often.
      Reactive mesothelial cells constantly repair the damages and keep the pleural
      cavity open. Without mesothelial cells, the lung cannot function properly and the
      pleural cavity will be quickly obliterated by fibrosis.

PMID- 9646979
TI  - Mechanical coupling and liquid exchanges in the pleural space.
AB  - The pleural space provides the mechanical coupling between lung and chest wall:
      two views about this coupling are reported and discussed. Information on volume,
      composition, thickness, and pressure of the pleural liquid under physiologic
      conditions in a few species is provided. The Starling pressures of the parietal
      pleura filtering liquid into pleural space, and those of the visceral pleura
      absorbing liquid from the space are considered along with the permeability of the
      mesothelium. Information on the lymphatic drainage through the parietal pleura
      and on the solute-coupled liquid absorption from the pleural space under
      physiologic conditions and with various kinds of hydrothorax are provided.

PMID- 9646980
TI  - CT and MR in pleural disease.
AB  - A number of different imaging modalities can be used in the assessment of pleural
      disease. Although ultrasound has been the more traditional method, CT has found
      increasing utility for the assessment of the empyema and loculated pleural fluid
      collections prior to drainage and the evaluation of benign and malignant pleural
      tumors. MRI has a limited but important role particularly in the evaluation of
      focal pleural tumors such as lipomas and in determining the extent of malignant
      mesothelioma prior to therapy.

PMID- 9646981
TI  - Evaluating diagnostic tests in the pleural space. Differentiating transudates
      from exudates as a model.
AB  - Physicians have a staggering variety of diagnostic tests available for directing
      their diagnostic and therapeutic decisions. Technologic advances in laboratory
      science have increased the sophistication of new tests and accelerated their rate
      of adoption into clinical practice. Unfortunately, studies that report the value
      of new diagnostic tests often fail to follow accepted methodologic standards for
      unbiased test assessment or provide clinicians with sufficient information for
      the intelligent evaluation of a test's performance and applicability. The
      following review of pleural fluid tests that discriminate between exudative and
      transudative effusions serves to highlight important methodologic considerations
      in the assessment of diagnostic tests.

PMID- 9646982
TI  - Diagnostic thoracoscopy.
AB  - Thoracoscopy provides diagnosis of pleural diseases with a high degree of
      accuracy. Moreover, this procedure allows a careful pleural staging of the
      disease, in particular for pleural cancer, which is important for the prognosis
      and therapeutic decision. This article focuses on the technique, indications, and
      results of medical thoracoscopy.

PMID- 9646983
TI  - Asbestos-induced pleural disease.
AB  - Asbestos-induced pleural disease has become the most common manifestation of
      asbestos exposure. Asbestos has an unusual affinity for the pleural space and
      leads to plaques, benign effusions, fibrosis, and malignant mesothelioma. The
      explanation for its affinity for the pleura may lie in part with new evidence
      showing that asbestos fibers can accumulate in certain regions of the parietal
      pleura at higher concentrations than in the lung. With the control of industrial
      exposures to asbestos, the incidence of this disease should decrease, with the
      incidence of mesothelioma peaking in the years 2000 to 2020. Nonetheless, the
      toxic features of asbestos including shape, chemical composition, and surface
      characteristics should be understood to avoid toxicity in fibers used to replace
      asbestos and to know the risks of low level exposures from asbestos currently in
      our environment.

PMID- 9646984
TI  - Drug-induced pleural disease.
AB  - Drug-induced pleural disease in the form of pleural fibrosis or pleural effusions
      is a common but frequently overlooked toxic or allergic manifestation of usage of
      a particular class of drugs. A detailed history of drug intake will often unveil
      the cause for the pleural pathology. Discontinuation of the drug with or without
      the addition of steroid therapy may be helpful.

PMID- 9646985
TI  - Pleural disease in patients with acquired immune deficiency syndrome.
AB  - Given the multiple impairments in host defense that occur during HIV infection,
      patients with AIDS are at risk for a variety of pleural infections and neoplasms.
      Of infectious causes, bacterial parapneumonic effusions and empyemas and
      tuberculous pleurisy occur more frequently than effusions caused by P. carinii.
      In each case, therapy is directed at eradication of the causative organisms. In
      the setting of systemic Kaposi's sarcoma, pleural involvement is common, although
      diagnosis is difficult and therapeutic options are limited. Pleural effusions
      caused by non-Hodgkin's lymphoma often occur in the setting of pulmonary
      parenchymal disease and can be diagnosed cytologically. The recently described
      entity of primary effusion lymphoma occurs in the absence of solid-organ
      involvement. The development of a spontaneous pneumothorax in a HIV-infected
      individual should prompt a search for P. carinii infection. Although these
      pneumothoraces often recur and are difficult to manage, recent series suggest
      that surgical approaches to bronchopleural fistulas are reasonable in selected
      patients.

PMID- 9646986
TI  - Malignancy metastatic to the pleura.
AB  - Malignancy is one of the most common causes of exudative effusions and increases
      in incidence in the elderly. Lung cancer is the most common cause of malignant
      effusion caused by contiguous spread and its propensity to invade the pulmonary
      vasculature and embolize to the visceral pleura. Lung, breast, ovary, and gastric
      cancer and lymphomas account for about 80% of all malignant effusions. Dyspnea
      and cough are the most common symptoms at presentation. Thirty percent of
      patients have a low pleural fluid pH (> or = 7.30) and glucose (> 60 mg/dL) at
      presentation, which predicts a decreased survival, an increase yield on
      diagnostic studies, and a poor response to chemical pleurodesis. Talc by poudrage
      or slurry is the most successful pleurodesis agent. Pleural peritoneal shunt is
      an option for patients with an intractable, symptomatic malignant effusion who
      cannot undergo or who have failed pleurodesis.

PMID- 9646987
TI  - Common pleural effusions in children.
AB  - The evaluation of pleural effusions in children differ from that of the adult in
      cause, symptom presentation, character of the fluid, techniques for diagnosis,
      treatment or management, and prognosis. These similarities and differences are
      reviewed with emphasis on the treatment of empyema.

PMID- 9646988
TI  - Management of parapneumonic effusions.
AB  - When a patient with a parapneumonic pleural effusion is first evaluated, a
      therapeutic thoracentesis should be performed if more than a minimal amount of
      pleural fluid is present. Fluid obtained at the therapeutic thoracentesis should
      be gram-stained and cultured and analyzed for glucose, pH, LDH, white blood
      cells, and differential cell count. If the fluid cannot be drained because of
      loculations, a chest tube should be inserted and thrombolytic agents
      administered. If the pleural fluid recurs after the initial therapeutic
      thoracentesis but the patient is doing well clinically and the initial pleural
      fluid glucose was greater than 60 mg/dL; the pH, greater than 7.2; the LDH, less
      than three times the upper normal limit for serum and the cultures are negative;
      he or she can be observed. If one or more of the aforementioned criteria are not
      met, a second therapeutic thoracentesis should be performed, with repeat
      diagnostic evaluations of the pleural fluid. If the fluid recurs a second time, a
      small chest tube should be placed if the pleural fluid glucose and pH were lower
      and the LDH higher on the second thoracentesis than on the first thoracentesis.
      Patients with loculated-parapneumonic effusions should be treated with tube
      thoracostomy and thrombolytic agents. If drainage is incomplete, thoracoscopy,
      with breakdown of adhesions and debridement of the pleural space, is indicated.
      If thoracoscopy is unsuccessful, then thoracotomy, with decortication, is
      indicated unless the patient is too debilitated.

PMID- 9646989
TI  - Therapeutic thoracoscopy.
AB  - Thoracoscopy provides a minimally invasive window to the pleural space, lung, and
      mediastinum. Further advances prompted by improvements of specifically designed
      endoscopic instruments and procedural techniques are expected. There is no doubt
      that thoracoscopy has a place among therapeutic procedures in the chest. The time
      proven principles of thoracic surgical intervention, particularly in regard to
      patients with cancer, however, must not be neglected. A beckoning window always
      offers new opportunities, but the open door of classic surgical techniques should
      not be ignored.

PMID- 9646990
TI  - Surgical management of empyema.
AB  - The cause and presentation of empyema thoraces has changed little since it was
      first described. The natural history of the disease can be divided into different
      stages. Different therapeutic measures, medical and surgical, are available for
      the treatment at various stages. The management of empyema is discussed,
      emphasizing the surgical aspects.

PMID- 9646991
TI  - Management of undiagnosed persistent pleural effusions.
AB  - Difficult to diagnose pleural effusions are not uncommonly encountered in
      clinical practice. We define these effusions as those that remain undiagnosed
      after initial thoracentesis and repeat thoracentesis with pleural biopsy.
      Tuberculosis and malignancy are often found to be the underlying causes when a
      diagnosis is ultimately made, but other causes, including pulmonary embolism and
      intra-abdominal conditions, need to be considered as potential causes of the
      difficult to diagnose effusions. In selected cases, presumptive treatment of
      tuberculosis is indicated whereas in others, a decision must be made either to
      obtain a definitive diagnosis by invasive surgical procedures or to follow the
      patient with careful observation and watchful waiting.

PMID- 9646992
TI  - The history of policy and practice related to the perinatal hospital stay.
AB  - The issue of early newborn discharge has received widespread attention in both
      the lay press and the medical literature over the past few years, culminating in
      passage of Public Law 104-204, Title VI: The Newborns' and Mothers' Health
      Protection Act of 1996. This article reviews the road to passage of this
      legislation, including the historical trends and forces determining postpartum
      length of stay in the United States, the evolution of guidelines as put forth by
      official representative bodies such as the AAP, the current status of state and
      federal legislation, and the relationship between length of stay and follow-up
      practices. The status of newborn length of stay in other countries also is
      discussed.

PMID- 9646993
TI  - The transition to extrauterine life and disorders of transition.
AB  - With shorter postnatal hospital stays, concern has arisen that many infants may
      be discharged prior to completion of the transition to extrauterine life, a time
      of dynamic physiologic change when many neonatal problems may present. This
      article reviews the physiology of the neonatal transition together with common
      transitional disorders. Most disorders of transition present at typical postnatal
      time periods, permitting their timely anticipation and treatment. Moreover, many
      are associated with factors that may further aid the clinician in defining those
      infants at highest risk.

PMID- 9646994
TI  - Jaundice in full-term and near-term babies who leave the hospital within 36
      hours. The pediatrician's nemesis.
AB  - There has been an increase in hyperbilirubinemia in the newborn population and,
      perhaps, an increase in bilirubin encephalopathy. The early discharge of newborns
      from hospital has made it necessary for us to reorient our thinking about
      bilirubin levels in the first 24 to 48 hours of life and alter our approach to
      follow-up. The pediatrician must evaluate and follow infants who have risk
      factors for the development of severe hyperbilirubinemia, paying particular
      attention to the breast-feeding, near-term infant.

PMID- 9646995
TI  - The optimization of breast-feeding in the perinatal period.
AB  - Mounting scientific evidence documents the diverse health benefits of successful
      breast-feeding for infants and mothers. The trend toward earlier discharge of
      newborns, however, has been linked with adverse outcomes in breast-fed babies,
      including hypernatremic dehydration and hyperbilirubinemia. This article reviews
      practical strategies for promoting the successful initiation of breast-feeding,
      beginning with effective prenatal education and a screening breast exam to detect
      lactation risk factors. Supportive hospital practices are discussed, including
      the Baby-Friendly Hospital Initiative and correct breast-feeding technique. The
      importance of regular, effective removal of milk for continued milk production is
      explained. The early follow-up of infants after hospital discharge and the use of
      specific maternal and infant criteria to assess the onset of breast-feeding can
      readily identify mother-baby pairs who require timely intervention to improve
      breast-feeding outcome.

PMID- 9646996
TI  - The newborn at risk for serious infections.
AB  - Early discharge of suitable newborns is rapidly becoming a hospital standard. One
      concern is that truncated hospital observation of the infant during the first
      days of life, even with home visits or early clinical appointments, would allow
      early signs of a serious infection to go unnoticed, which could lead to a missed
      chance for early therapy and could imperil the child's favorable recovery. An
      analysis of available data for early onset neonatal bacterial sepsis and neonatal
      herpes virus infection shows that this new practice should not unduly place
      newborns at risk of treatable infections, however, so long as conventional risk
      factors are appreciated and reasonable, nationally sanctioned discharge criteria
      are followed.

PMID- 9646997
TI  - The drug-exposed infant in the well-baby nursery.
AB  - Maternal substance use can have medical and developmental consequences for the
      newborn. Many drug-exposed infants are admitted to term nurseries, and the
      newborn clinician who often has never previously met the mother must gather both
      objective and subjective information about problems in the pregnancy and delivery
      that may indicate maternal substance abuse. This article addresses the prevalence
      of maternal substance abuse in the United States, the long-term consequences of
      in utero drug exposure that makes early identification important, the
      identification of a drug-exposed neonate, and in-hospital care and discharge
      management of the drug-exposed newborn.

PMID- 9646998
TI  - Congenital malformations presenting during the neonatal period.
AB  - Discharge of the newborn within 24 to 48 hours after birth makes it more
      difficult to detect some congenital malformations and increases the need for
      careful examination and review of the history of the pregnancy, delivery, and
      nursery course. Progressive physiologic changes after birth, especially in the
      cardiovascular system, precede the development of signs indicative of disease for
      certain congenital malformations. Discharge before these changes occur may delay
      their detection because the newborn is not being monitored by medical or nursing
      caregivers. The AAP Committee on the Fetus and Newborn has published guidelines
      for criteria for safe discharge and follow-up evaluation to help create a safe
      situation for such early discharges. Some specific observations at birth may lead
      to earlier diagnosis. Careful attention to subtle differences between the initial
      and follow-up examination, such as a changing cardiac murmur or quality of pulses
      or abdominal fullness, may provide clues to the diagnosis of congenital
      malformations. Coordinated suck and swallow with successful feeding and passage
      of stool and urine within 24 hours after birth should occur before discharge.
      Reports of feeding difficulties should be reviewed. Although a thorough
      examination is facilitated by a sleeping infant, documentation of a normal
      pitched cry helps in the evaluation of the upper airway. Parents should be
      counseled about signs of illness that warrant medical attention, and early follow
      up is needed to detect problems early enough to intervene effectively. In
      addition, although passage of a feeding tube through each nare and to the stomach
      with aspiration and measurement of gastric volume is not a routine procedure in
      the well, term newborn, this may be a useful early diagnostic tool in infants
      with signs or a maternal or nursery history suggestive of nasal or GI
      obstruction.

PMID- 9646999
TI  - Metabolic screening.
AB  - Mandated, universal metabolic screening has been an effective tool for the early
      identification of infants with metabolic disorders, particularly those amenable
      to improved outcome with dietary management or medication. Although the
      availability of diagnosis long before symptoms occur may be useful to preclude
      expensive diagnostic evaluation when the subtle early symptoms begin and may
      allow for genetic counseling and testing in affected families, many concerns have
      been raised regarding the psychologic impact of presymptomatic diagnosis of
      diseases that are either fatal or for which no effective treatment is available.
      Before mass screening is initiated, careful pilot studies need to be done to
      evaluate sensitivity and specificity as well as the impact of early
      identification on infant outcome.

PMID- 9647000
TI  - Maternal education during the perinatal period.
AB  - The nature of perinatal education has been transformed, reflecting the changes in
      health care and health care consumers. Because of short maternity stays, the
      venue of most perinatal education, especially postpartum education, has moved
      from hospitals to other areas, including the home. In light of conflicting
      findings of past research examining the effectiveness of prenatal education as
      well as gaps in the literature, there is a need for research on the content,
      methods, providers, and dose effect of perinatal education.

PMID- 9647001
TI  - Medical conditions of the puerperium.
AB  - The puerperium is a time of continued, dramatic pregnancy-associated adaptation.
      Although much less common than in the early part of the century, maternal death
      can still occur from common postpartum problems such as infection, hemorrhage,
      and disease. This article reviews the physiologic and emotional changes as well
      as the clinical management of common problems in the puerperium.

PMID- 9647002
TI  - The perinatal assessment of psychosocial risk.
AB  - Although evaluation of psychosocial risk factors prior to perinatal hospital
      discharge has been advocated, the means for accomplishing such an evaluation are
      not well established. This article reviews several major psychosocial risk
      factors together with instruments that have been utilized to assess them during
      the perinatal period. Formal constructs reviewed include anxiety, depression,
      self-concept, general attitudes, life events, stress, adaptation, social support,
      marital and family functioning, and the home environment. Ongoing assessment of
      psychosocial status using formal instruments during routine perinatal care may
      provide a more complete picture of the psychosocial needs of the individual
      mother and her family, allowing for more appropriate, timely intervention and
      utilization of social and health care resources.

PMID- 9647003
TI  - Perinatal screening for child abuse and neglect.
AB  - An increased awareness of the frequency and severity of child abuse and neglect
      in our society has prompted consideration of the feasibility of perinatal
      screening and early intervention for this problem. This article reviews the
      available information on screening and early intervention for high-risk parenting
      in the perinatal period. The advantages, disadvantages, and cost-effectiveness of
      screening and intervention for children and families at risk for abuse and
      neglect are also discussed.

PMID- 9647004
TI  - Assessing parent-infant interaction during the perinatal period. Some cautions.
AB  - Pediatricians have recently been urged by professional groups to pay increased
      attention to parental behavior when serving and discharging newborns. These
      exhortations are well intended, but they may reflect a misunderstanding of
      developmental processes and foster a mistaken belief in the ease with which
      parenting problems can be identified and remedied. This article describes how
      early experiences affect children's development and then contrasts this view with
      a popular perspective based on misapplication of the medical model to the
      conceptualization of behavioral development.

PMID- 9647005
TI  - Follow-up of newborns and their mothers after early hospital discharge.
AB  - As postpartum hospital stays have become increasingly shorter, more attention has
      been focused on the importance of routine postdischarge follow-up for newborns
      and mothers. Recent guidelines and legislation, however, include few specifics on
      how follow-up services should be provided. Based on the authors' review of the
      recent literature, it was concluded that the research to date provides little
      useful information to guide follow-up practices under current conditions.
      Additional studies that focus on postdischarge follow-up, rather than on length
      of hospital stay, are needed to provide the basis for more specific practice
      guidelines.

PMID- 9647006
TI  - Economic aspects of the perinatal hospital stay.
AB  - This article concentrates on the economics of the perinatal hospital stay for
      normal vaginal and cesarean section deliveries. Published studies in the United
      States are reviewed under three headings: inpatient costs for traditional stays,
      outpatient costs for postpartum services, and costs for short stays with follow
      up services. Despite the increasing attention on length of stay after delivery,
      there has been minimal research examining the true costs of an early discharge
      program and services compared with longer hospital stays. Formal analysis of
      alternative strategies and well-designed clinical studies are needed before an
      optimal policy for caring for mothers and infants can be identified.

PMID- 9647007
TI  - Early discharge of premature infants. A critical analysis.
AB  - Although significant advances in the medical management of acutely ill preterm
      infants have resulted in unprecedented rates of survival, issues surrounding the
      convalescent care, discharge preparation, and readiness of parents or other
      caregivers have been less well studied and represent the art of medicine. Recent
      consensus statements provide a degree of content validity; however, important
      areas of scientific inquiry remain. Much is left to understand about the
      pathophysiology, management, and outcomes of apnea, bradycardia, and oxygen
      desaturation episodes continuing at term. Why do the most immature infants have a
      delay in the maturation of respiratory control? Do breathing studies really
      provide information that predicts subsequent respiratory control abnormalities?
      If methylxanthines are used at discharge, what criteria should be adhered to
      regarding their discontinuation? How is nutrition best provided while
      transitioning to home? In infants whose mothers desire exclusive breast-feeding,
      should gavage feeds be used to supplement in order to avoid bottle-feedings? How
      long should breast milk be fortified, and when should supplemented artificial
      milks be used and for what period of time postdischarge should these more
      expensive special-discharge artificial milks be used? What other supplements,
      such as inositol, vitamins, or antioxidants, should be provided in order to
      achieve optimal growth and development? Technology-dependent infants pose even
      greater complexities. Some infants and families adapt to extensive use of
      technology in the home. In other situations, basic infant care is difficult to
      achieve. What are the essential components for successful early discharge, and
      how can the studies involving selected families be made universal? How can NICUs
      better prepare fathers and mothers for premature parenthood? To what extent are
      we overwhelming families with additional responsibilities and expectations that
      may compromise their competency in basic parenting? Furthermore, the degree of
      provider variation in evaluating and providing for discharge planning is now
      being more carefully studied. In some circumstances, integrated teams in the NICU
      have facilitated the discharge process saving days of hospitalization, whereas in
      others adherence to discharge planning guidelines has lengthened the stay in the
      NICU and resulted in higher costs. What is the ideal system for achieving
      coordination of care without co-opting parental choices in assuming more care
      responsibility than is comfortable? In the design of tertiary care facilities,
      more attention to space for rooming-in experiences needs to receive greater
      priority. Furthermore, because of intensity of care, adverse environmental
      stimuli, and for issues of better resource utilization, should not most
      previously ill infants be discharged from level II or intermediate care centers?
      Finally, issues of increasing decision-making responsibility placed on parents
      (with the reassurance and guiding hand of dedicated physicians and nurses focused
      on individual infants) must never be made subservient to the economic whims of
      insurers to decrease costs without understanding the value of the entirety of the
      care process for critical illness, through convalescence, to it is hoped a
      supportive and nurturing environment in the home. Our patients deserve no less.
      The questions posed present a sample of issues yet to be scientifically
      addressed. These and many other questions need to be answered before we fully
      understand the optimal process of discharge for the preterm infant.

PMID- 9647008
TI  - Successful antiviral therapy and prognosis in cirrhosis due to hepatitis B.

PMID- 9647009
TI  - Teaching irritable bowel syndrome patients to care for themselves.

PMID- 9647010
TI  - The origin of 20th century discoveries transforming clinical gastroenterology.

PMID- 9647011
TI  - Performing a cost-effectiveness analysis: surveillance of patients with
      ulcerative colitis.
AB  - OBJECTIVE: To illustrate the principles of cost-effectiveness analysis, this
      third article in the "Primer on Economic Analysis for the Gastroenterologist"
      applies published criteria for appraising an economic analysis to a study of the
      cost-effectiveness of surveillance of patients with ulcerative colitis. METHODS:
      We review and apply the 10 standard criteria for critical appraisal and
      evaluation of cost-effectiveness analyses. SUMMARY: We outlined the development
      and critique of a decision analytic model that examines the cost-effectiveness of
      surveillance of patients with ulcerative colitis, and we compared the cost
      effectiveness of surveillance of patients with ulcerative colitis to other well
      accepted medical practices.

PMID- 9647012
TI  - Gastrointestinal manifestations of Chagas' disease.
AB  - Chagas' disease is an infectious disease that affects millions of people in Latin
      America and is increasingly seen outside endemic areas. A substantial number of
      patients develop gastrointestinal disorders secondary to lesions of the enteric
      nervous system. The purpose of this article is to review the current knowledge
      about gastrointestinal manifestations of Chagas' disease, including disorders
      other than the well-known gross dilations of esophagus and colon.

PMID- 9647013
TI  - The watermelon stomach: clinical presentation, diagnosis, and treatment.
AB  - The watermelon stomach syndrome is an increasingly recognized cause of persistent
      acute or occult gastrointestinal bleeding, typically in elderly women. This
      disorder often presents with severe iron deficiency anemia, and a variety of
      associated conditions including autoimmune disease, cirrhosis, achlorhydria, and
      hypochlorhydria. Diagnosis is made by the characteristic endoscopic appearance of
      visible linear watermelon-like vascular stripes in the antrum. Histology confirms
      the vascular nature of this disorder, showing dilated and thrombosed capillaries
      in the lamina propria, associated with reactive fibromuscular hyperplasia. The
      optimum treatment of choice is not known. Several treatment options, including
      surgical antrectomy, and endoscopic photocoagulation with Nd:Yag laser, heater
      probe therapy, and bipolar electrocautery, have yielded excellent results.
      Pharmacological agents have also been used to treat selected numbers of patients,
      most of which comprise a small number of case reports.

PMID- 9647014
TI  - Delayed clearance of serum HBsAg in compensated cirrhosis B: relation to
      interferon alpha therapy and disease prognosis. European Concerted Action on
      Viral Hepatitis (EUROHEP)
AB  - OBJECTIVE: The aim of this study was to evaluate the incidence, prognostic
      factors and clinical significance of delayed clearance of serum HBsAg in
      compensated cirrhosis B. METHODS: This was a retrospective cohort study of 309
      consecutive white patients with biopsy-proved compensated cirrhosis type B.
      RESULTS: During a mean follow-up of 68 months, HBsAg loss occurred in 32
      patients, including 16 (8%) of 196 untreated patients (mean annual incidence
      0.8%), 8 (10%) of 82 interferon (IFN) alpha-treated patients and eight patients
      who had been treated with other antivirals or steroids. The 5-yr probability of
      HBsAg loss was 4% and 16% for untreated and IFN-treated patients, respectively (p
      = 0.0001). Cox's regression analysis identified hepatitis B e antigen-positivity
      at entry as the sole independent prognostic factor for HBsAg loss. Of the 32
      patients who lost HBsAg, one (3%) subsequently developed hepatocellular carcinoma
      (HCC) and died, whereas, among the patients who remained HBsAg-positive, 11%
      developed HCC and 20% had died. The probability of HCC appearance was lower (p =
      0.0137) and survival was longer (p = 0.0006) in patients who cleared HBsAg
      compared with patients with HBsAg persistence. CONCLUSION: The incidence of HBsAg
      loss is about 0.8% in cirrhosis type B. Prognostic factors for clearance of HBsAg
      are initial HBeAg positivity and therapy with alpha interferon. Patients with
      cirrhosis type B, who lose HBsAg, have a low risk for liver cancer or liver
      related death.

PMID- 9647015
TI  - Effects of an irritable bowel syndrome educational class on health-promoting
      behaviors and symptoms.
AB  - OBJECTIVE: The degree to which patient education in the areas of diet, exercise,
      and stress management can improve symptoms of irritable bowel syndrome (IBS)
      through healthier lifestyle behaviors is unknown. The aim of this study was to
      determine the effects of outpatient education on the short and long term
      outcomes, and the association between health-promoting behaviors and symptoms.
      METHODS: Pender's Health Promotion Model provided the theoretical framework. The
      study had a prospective longitudinal design. A consecutive sample of 52 adult
      outpatients with IBS attended a structured class that taught health-promoting
      modifications of lifestyle. Participants completed the Health-Promoting Lifestyle
      Profile (HPLP) and selected items from a Bowel Disease Questionnaire (BDQ) before
      the class and 1 month and 6 months later. Spearman rank correlations were used to
      assess the association between HPLP and symptom scores. Wilcoxon rank sum tests
      compared changes in scores versus their baseline values. RESULTS: Response rates
      at 1 and 6 months were 75% and 83%, respectively. Results revealed significant 1-
      and 6 month-improvements in pain and Manning symptoms (p < 0.01) and in some HPLP
      scores (exercise at 1 month, p < 0.05; stress management at 6 months, p < 0.01).
      Significant associations were found between some, but not all, HPLP and symptom
      scores over time. CONCLUSION: A structured IBS educational class for patients
      with IBS improved symptoms and some health-promoting behaviors. However,
      relationships among specific behaviors and specific symptoms did not consistently
      correspond with this improvement.

PMID- 9647016
TI  - Effectiveness and patient satisfaction with nurse-directed treatment of Barrett's
      esophagus.
AB  - OBJECTIVE: Using clinical practice guidelines, a registered nurse adjusted
      antireflux medications, evaluated esophageal biopsy reports, determined the
      interval between surveillance endoscopies, and provided education for patients
      with Barrett's esophagus. No previous reports have assessed the effectiveness or
      patient satisfaction associated with registered nurse-provided primary care.
      Because estimates of the incidence of dysplasia and adenocarcinoma vary widely,
      we also prospectively followed a cohort of patients with Barrett's esophagus.
      METHODS: Charts were reviewed to determine the frequency of variation from
      guidelines, the annual incidence of dysplasia and adenocarcinoma, and frequency
      of reflux symptoms. Patients were mailed a questionnaire to assess satisfaction
      with their medical care and with the nurse. RESULTS: Variation by the nurse from
      the guidelines on surveillance endoscopy (1.9%) and the treatment of reflux
      (1.3%) was rare. Most patients were very satisfied (score of 6 on 0-6-point
      Likert scale) with overall medical care (88%), and patient education (76%), and
      most patients did not think that increased physician involvement would improve
      their care (93%). Ninety-seven percent of patients had control of reflux
      symptoms. Two patients with long segment Barrett's esophagus (n = 67) developed
      high grade dysplasia over 323 patient-yr of follow-up (1 of 162 patient-yr for an
      annual incidence of 0.6%). No patients with short segment Barrett's esophagus (n
      = 56) developed high grade dysplasia or adenocarcinoma over 172 patient-years of
      follow-up. CONCLUSION: The registered nurse in our clinical setting effectively
      administered clinical practice guidelines for the management of Barrett's
      esophagus without clinically significant morbidity or patient dissatisfaction.
      Before these results can be generalized to other settings, further studies will
      need to be performed.

PMID- 9647017
TI  - Endoscopic surveillance of Barrett's esophagus: a cost-effectiveness comparison
      with mammographic surveillance for breast cancer.
AB  - OBJECTIVE: Endoscopic surveillance of Barrett's esophagus is commonly practiced
      to detect malignancy in an early and curable stage. However, the cost
      effectiveness of this practice has been questioned. To clarify this issue, we
      undertook a cost analysis of endoscopic surveillance to detect adenocarcinoma in
      Barrett's esophagus compared with mammography used to detect occult carcinoma of
      the breast, a widely accepted cancer surveillance technique. METHODS: The rate of
      esophageal adenocarcinoma detected by endoscopic surveillance was calculated for
      Duluth Clinic patients with Barrett's esophagus seen from 1980 to 1995 and
      compared with published rates. The rate of occult breast cancer detection was
      calculated for all women undergoing surveillance mammography at the Duluth Clinic
      for the year 1994 and compared with published rates. Costs for screening studies
      and therapy for cancer treatment for both cancers were calculated based on
      clinical results and assumptions regarding outcomes derived from published
      reports, and the costs were compared. RESULTS: Endoscopic surveillance of 149
      patients with benign Barrett's esophagus was performed for a total of 510 patient
      yr, during which time seven patients developed adenocarcinoma, an incidence of
      one case per 73 patient-yr of follow-up. Occult breast cancer was detected in 50
      of 12,537 mammograms, a detection rate of 0.4%. The incidences in both cases were
      comparable to published figures. The costs of detecting a case of adenocarcinoma
      in Barrett's esophagus and occult breast cancer were $37,928 and $54,513,
      respectively, and those for treatment resulting in cure were $83,340 and $83,292.
      Cost per life-yr saved was $4,151 for adenocarcinoma in Barrett's esophagus and
      $57,926 for breast cancer. CONCLUSION: Endoscopic surveillance of patients with
      Barrett's esophagus compares favorably with the common practice of surveillance
      mammography to detect early breast cancer, and should therefore be considered to
      be as cost-effective as surveillance mammography.

PMID- 9647018
TI  - Esophageal manometry and ambulatory 24-hour pH monitoring in patients with short
      and long segment Barrett's esophagus.
AB  - OBJECTIVE: Short segment Barrett's esophagus (SSBE) is defined as the presence of
      specialized intestinal metaplasia (SIM) in the distal 2-3 cm of the esophagus.
      Although gastroesophageal reflux and heartburn is very common in these patients,
      the pathophysiology of the development of a short segment of SIM versus a longer
      segment of Barrett's epithelium is not clear. The aim of this study was to assess
      the extent of gastroesophageal reflux in short versus long segments of SIM.
      METHODS: Of 203 consecutive patients undergoing endoscopy with two biopsies
      performed just distal to the squamocolumnar junction, 28 patients were identified
      as having SSBE as evidenced by SIM on biopsy. Twenty-two SSBE patients underwent
      esophageal manometry and 24-h dual pH monitoring, and the results were compared
      with 18 long segment Barrett's esophagus (LSBE) patients and 15 patients with
      normal 24-h pH studies. RESULTS: SSBE and LSBE patients were significantly older
      than normal subjects (p < 0.0001). Also, lower esophageal sphincter pressure was
      significantly greater in SSBE patients compared with LSBE patients (12.3 +/- 1.6
      vs 5.2 +/- 1.0 mm Hg,p < 0.0008). LSBE patients had a significantly lower distal
      esophageal peristaltic amplitude as compared with normals (p < 0.012). At 5 cm
      proximal to the LES, SSBE patients had significantly lower total 24-h pH scores,
      percent upright and percent supine reflux as compared with LSBE patients.
      Similarly, when measured at the proximal LES (0 cm), SSBE patients had
      significantly lower 24-h pH scores when compared with LSBE patients (p < 0.03),
      whereas percent upright and percent supine reflux were not significantly
      different. Both LSBE and SSBE patients had a greater degree of GER measured at 5
      cm above and just proximal to the LES when compared with normals. CONCLUSION: As
      a group, SSBE patients have more competent LES sphincters and less
      gastroesophageal reflux at 0 and 5 cm above the LES as compared with patients
      with LSBE. These data indicate that the degree and length of acid exposure in the
      esophagus are important factors in the pathogenesis of SIM involvement of the
      esophagus.

PMID- 9647019
TI  - Managing dyspepsia: what do we know and what do we need to know?
AB  - OBJECTIVE: The conceptual revolution concerning the role of Helicobacter pylori
      in the pathogenesis of peptic ulcer disease has raised the larger question of how
      to integrate this new information into the management of patients with dyspepsia.
      The aim of this research was to critically evaluate current knowledge about
      dyspepsia and its management. METHODS: Relevant articles on dyspepsia were
      identified from MEDLINE searches and from the bibliographies of identified
      articles. Studies that contained information on the prevalence of dyspepsia,
      endoscopic findings, and evaluations of alternative management strategies were
      reviewed. RESULTS: By coupling H. pylori serological testing with clinical
      factors such as age and nonsteroidal antiinflammatory drug use, strategies have
      been developed that identify patients with organic disease. Although the use of
      these strategies can reduce the volume of endoscopies, their effects on dyspepsia
      symptoms are unknown. Computerized decision analysis models have been used to
      evaluate the cost-effectiveness of alternative strategies. The indirect evidence
      obtained from these models suggests that empiric therapy, guided by H. pylori
      testing, may be the preferred approach. However, the models have been hampered by
      the lack of information concerning dyspepsia symptoms, the primary health outcome
      of the majority of patients seen in primary practice settings. CONCLUSIONS:
      Currently, the knowledge needed to integrate H. pylori tests and antimicrobial
      therapies into the management of patients with dyspepsia in primary practice
      settings has not been developed. A pressing need exists for a randomized
      controlled trial to evaluate alternative management strategies. In conducting
      such a trial, valid, reliable instruments for measuring dyspepsia will be needed.

PMID- 9647020
TI  - Eradication of Helicobacter pylori reduces the rate of duodenal ulcer rebleeding:
      a long-term follow-up study.
AB  - OBJECTIVES: The long-term efficacy of Helicobacter pylori eradication to reduce
      the rate of recurrence of peptic ulcer bleeding is still uncertain. We evaluated
      the rate of duodenal ulcer rebleeding for 48 months after H. pylori eradication.
      METHODS: Thirty-two male patients with H. pylori infection and duodenal ulcer
      bleeding were treated with omeprazole (40 mg/day for 4 wk), colloidal bismuth
      (480 mg/day for 2 wk), amoxicillin (2 g/day for 1 wk), and metronidazole (750
      mg/day for 1 wk), and followed up for 48 months. Endoscopy and tests for H.
      pylori infection were repeated every year. RESULTS: Ulcer healed in all patients,
      but H. pylori infection persisted or recurred in 11 patients. Within 48 months,
      rebleeding occurred in nine (81.8%) of these patients, whereas the 21 patients
      who were persistently negative for H. pylori infection remained asymptomatic
      without rebleeding (0/ 21 = 0%, p < 0.002) during the whole follow-up.
      CONCLUSIONS: Eradication of H. pylori can reduce the rate of duodenal ulcer
      rebleeding for at least 4 yr, thus potentially modifying the natural history of
      the disease.

PMID- 9647021
TI  - Ulcer recurrence after gastric surgery: is Helicobacter pylori the culprit?
AB  - OBJECTIVES: Helicobacter pylori is the most important cause of recurrent peptic
      ulcer disease. However, its role in ulcer recurrence after peptic ulcer surgery
      is unclear. We aimed at studying the prevalence and distribution of H. pylori in
      patients who had undergone peptic ulcer surgery, and any association between H.
      pylori infection and ulcer recurrence in these patients. METHODS: Patients with
      previous vagotomy or partial gastrectomy presenting with dyspepsia or ulcer
      bleeding were recruited. Ulcer recurrence was documented by endoscopy. Biopsy
      specimens were taken from the gastric remnant and gastroenteric anastomosis in
      patients with previous partial gastrectomy, or from the antrum and corpus in
      vagotomized patients. H. pylori infection was detected by either a positive rapid
      urease test or the presence of the bacteria on histology. RESULTS: Ninety-three
      patients were studied; 73 patients (78%) had partial gastrectomy and 20 (22%) had
      vagotomy with drainage. H. pylori infection was documented in 36 patients (49%)
      in the gastrectomy group and in 13 (65%) in the vagotomy group. Thirty-six
      patients in the gastrectomy group had recurrent ulcers and 15 (42%) of them had
      H. pylori infection. Twelve patients in the vagotomy group had recurrent ulcers
      and eight (67%) of them were H. pylori positive. The prevalence of H. pylori
      infection did not differ between patients with or without ulcer recurrence.
      CONCLUSION: H. pylori infection cannot account for ulcer recurrence after peptic
      ulcer surgery.

PMID- 9647023
TI  - Prevalence and etiology of gastroduodenal ulcer in HIV-positive patients: a
      comparative study of 497 symptomatic subjects evaluated by endoscopy.
AB  - OBJECTIVE: In 497 HIV-positive (+) patients with upper digestive tract symptoms,
      23 (5%) had gastroduodenal ulcers (GDU) at upper endoscopy. METHODS: To establish
      the causes of GDU in this setting, 16 of these patients who had had comprehensive
      histological evaluation (group I) were compared with 20 HIV+ subjects with upper
      gastrointestinal symptoms but without ulcer (group II), and with 16 seronegative
      patients with GDU (group III). Eighty-one percent of group I subjects and 90% of
      group II patients had C3 AIDS. The presence of gastritis and Helicobacter pylori,
      fungi, mycobacteria, viruses (especially cytomegalovirus [CMV] and herpes simplex
      [HSV]), and parasites was determined in all three groups by histopathological and
      microbiological studies. RESULTS: The prevalence of chronic active gastritis was
      13/16 (81%) in group I, 12/20 (60%) in group II, and 15/16 (94%) in group III. It
      was associated with H. pylori in group III, and with opportunistic pathogens in
      groups I and II and with none in group III. H. pylori was detected in 5/16
      patients (31%) in group I, in 12/20 (60%) in group II, and 11/16 (69%) in group
      III. Cytomegalovirus was histologically diagnosed in 8/16 patients (50%) in group
      I and in 1/20 (5%) in group II. This virus was the only factor shown to be
      significantly associated with GDU in these cases (p = 0.0046). Cryptosporidium
      was found in 2/16 (12.5%) patients in group I, in 1/20 (5%) in group II, and in
      none in group III. Differences between groups I and II were not statistically
      significant. No other organisms were observed in the three groups. CONCLUSIONS:
      Gastroduodenal ulcers were infrequent in HIV+ subjects with upper digestive tract
      symptoms and CMV was the only organism significantly associated with GDU in HIV+
      patients. Among HIV+ patients, H. pylori was an uncommon cause of ulcer. Among
      HIV+ subjects with ulcer, chronic active gastritis was more common than H. pylori
      and it was associated with other pathogens. Finally, HIV+ patients with GDU
      should have endoscopic biopsies to detect opportunistic infections, especially
      CMV, because H. pylori infection is uncommon.

PMID- 9647022
TI  - Two-day quadruple therapy for cure of Helicobacter pylori infection: a
      comparative, randomized trial.
AB  - OBJECTIVE: We sought to compare a 2-day quadruple therapy with a 14-day triple
      therapy in the treatment of Helicobacter pylori infection. METHODS: Eighty-one
      consecutive patients with an endoscopically diagnosed peptic ulcer and
      demonstrated infection by H. pylori were included in the study. Patients were
      randomized to receive omeprazole 40 mg b.i.d., amoxicillin 2.5 g once daily,
      metronidazole 500 mg t.i.d., and bismuth subcitrate 360 mg t.i.d. for 2 days,
      followed by omeprazole 20 mg once daily for 6 additional days (Group 1) or a 14
      day course of omeprazole 20 mg b.i.d., amoxicillin 1 g t.i.d., and metronidazole
      500 mg t.i.d. (Group 2). Eradication was evaluated by antral biopsy and rapid
      urease test at 2 months after therapy and by C13-urea breath test after a year.
      RESULTS: Two patients were lost to follow-up at 2 months. Intention-to-treat
      analysis showed that H. pylori infection was cured in 29 of 42 patients (69%; 95%
      CI: 53-82%) in Group 1 versus 36 of 39 (92%; 95% CI: 78-98%) of patients in Group
      2 (p = 0.009). Per-protocol analysis showed a cure rate of 71% (95% CI: 55-84%)
      (29/41 patients) and 95% (95% CI: 81-99%) (36/38 patients), respectively (p =
      0.007). Fifty-five of 65 cured patients returned 1 year after treatment (26 in
      Group 1, 29 in Group 2). All but one in Group 2 remained cured. There were no
      significant differences in compliance (88% in Group 1 versus 92% in Group 2) or
      in the presence of side effects (27%; 95% CI: 15-43% versus 41%; 95% CI: 26-58%;
      ns). CONCLUSION: Two-day quadruple therapy is significantly less effective than 2
      wk triple treatment.

PMID- 9647024
TI  - Percutaneous sonographic gastrostomy: method, indications, and problems.
AB  - OBJECTIVES: This study evaluated the application of ultrasound (US) guidance in
      the percutaneous placement of gastric feeding tubes in patients in whom
      endoscopic placement of a nutrition tube is not possible. METHODS: Thirty-eight
      patients with upper gastrointestinal obstruction were entered in a prospective
      study with US-guided nutrition tube application. Feasibility of placement, side
      effects, and nutritional states were monitored for a mean follow-up of 4 months.
      RESULTS: Ultrasound allowed rapid puncture after filling of the stomach with
      water through a nasal tube in 34/38 cases. In four cases a total upper
      gastrointestinal obstruction required an initial stomach insufflation through a
      direct puncture. Puncture-related major complications were not observed. Minor
      complications during the observation time were one late dislocation, five cases
      with broken material after about 6 months (four could be changed by using the
      Seldinger technique), and two minor local infections. The nutrition through
      feeding tubes stabilized body weight and body composition parameters. CONCLUSION:
      The percutaneous sonographic gastrostomy (PSG) is a safe and minimally invasive
      procedure for enteral nutrition in all cases with upper gastrointestinal
      obstruction when endoscopic placement of a feeding tube is not possible.
      Percutaneous sonographic gastrostomy may help to stabilize the nutritional
      parameters and general condition in patients with malignant diseases.

PMID- 9647025
TI  - Gastroesophageal reflux in patients fed by percutaneous endoscopic gastrostomy
      (PEG): detection by a simple scintigraphic method.
AB  - OBJECTIVES: Gastroesophageal scintigraphy has been described as a sensitive and
      accurate way to detect and quantitate gastroesophageal reflux (GER). Our
      objectives here were to evaluate the usefulness of a modified scintigraphic
      technique in the detection of GER and lung aspiration in patients fed by
      percutaneous endoscopic gastrostomy (PEG), and to assess the incidence of GER
      after insertion of PEG. Further, we sought to examine whether or not the
      underlying cause of dysphagia plays any significant part in the causation of GER.
      METHODS: Twenty-two patients, 13 with neurological dysphagia and nine with
      mechanical dysphagia, were studied. Each patient received 25 MBq of Tc-99m-tin
      colloid in orange juice followed by 300 ml of normal saline through the PEG tube.
      Dynamic and static images were taken immediately and at 4 h over esophagus,
      stomach, and lungs. RESULTS: Twelve patients (10 with neurological dysphagia) had
      GER and one had aspiration into the lungs. In all but one patient GER occurred in
      the immediate postprandial period. CONCLUSIONS: Scintigraphy is useful in
      assessing GER in PEG-fed patients. We also note that GER is a major problem in
      patients with PEG, especially in those with neurological dysphagia.

PMID- 9647026
TI  - Intravenous natural beta-interferon in white patients with chronic hepatitis C
      who are nonresponders to alpha-interferon.
AB  - OBJECTIVES: alpha-Interferons (alpha-IFN) have been shown to be effective in the
      treatment of chronic viral C hepatitis, but their efficacy remains
      unsatisfactory. Recently natural beta-interferon (beta-IFN) administered by
      intravenous infusion has been used successfully. METHODS: To evaluate the
      efficacy and safety of intravenous beta-IFN administration we treated 20 patients
      with histologically proven chronic hepatitis C who were nonresponders to at least
      two previous courses of alpha-IFN treatment. All patients received 6 million
      units (MU) of natural human fibroblast beta-IFN by drip infusion, 6 times per wk
      for 8 wk and were followed up for 6 months after suspension of treatment.
      RESULTS: Five patients (25%) had response at the end of treatment; of these
      patients only one had sustained response. Patients who responded to therapy had
      lower, although not significantly, baseline levels of HCV RNA, compared with
      nonresponders. Whereas mean viral load decreased during therapy, only two
      patients were HCV RNA negative at the end of treatment, but none were at the end
      of the follow-up period. Genotype 1 was found in 17 cases, genotype 2 was found
      in one case, and a combination of genotypes 1b and 2a was found in the remaining
      two cases. Therapy was well tolerated and beta-IFN administration was neither
      interrupted nor its dosage reduced due to side effects in any of the patients.
      CONCLUSIONS: Our study shows that intravenous beta-IFN is well tolerated and that
      the modest results obtained may depend on the brevity of treatment. Consequently,
      further studies are needed to define the optimum dose, schedule, and duration of
      treatment to eradicate HCV infection.

PMID- 9647027
TI  - Significance of elevated IgG anticardiolipin antibody levels in patients with
      Budd-Chiari syndrome.
AB  - OBJECTIVES: Budd-Chiari syndrome (BCS) is characterized by hepatic venous outflow
      obstruction. Though hypercoagulable states are implicated in the causation of
      BCS, the etiology remains unknown in most cases. Presence of anticardiolipin
      antibodies (aCL) is a known cause of hypercoagulable state. We therefore studied
      the frequency of IgG aCL in BCS. METHODS: Sera were obtained from 19 patients
      with BCS, 50 healthy controls, 18 age- and gender-matched patients with
      cirrhosis, and 15 patients with acute viral hepatitis. IgG aCL levels were
      measured using a solid-phase enzyme immunoassay. Values exceeding mean + 2 SD of
      healthy controls were taken as abnormal. RESULTS: Mean +/- SD IgG aCL levels (GPL
      units) in the four groups were: healthy controls, 6.3 +/- 4.4; BCS, 13.8 +/- 13.3
      (p < 0.05, compared with healthy controls); cirrhosis, 15.1 +/- 14.9 (p < 0.05,
      compared with healthy controls and p = ns, compared with BCS patients); and acute
      viral hepatitis, 5.0 +/- 2.5 (p = ns, compared with healthy controls). The levels
      in BCS and cirrhosis patients were similar (p = ns). The number of patients with
      elevated aCL was: healthy controls, 3/50; BCS, 6/19; cirrhosis, 7/18; and acute
      viral hepatitis, 0/15. The number of patients with elevated IgG aCL was
      significantly higher among patients with BCS and cirrhosis, compared with
      controls (p = 0.03 and p = 0.002, respectively). CONCLUSIONS: Patients with BCS
      had higher IgG aCL levels than healthy controls. However, as aCL levels were also
      elevated in patients with cirrhosis, the pathogenetic role of IgG aCL in the
      causation of BCS is doubtful.

PMID- 9647028
TI  - Autoimmune conditions associated with primary biliary cirrhosis: response to
      ursodeoxycholic acid therapy.
AB  - OBJECTIVES: A variety of autoimmune conditions occur in association with primary
      biliary cirrhosis. Among these conditions are sicca syndrome, Raynaud's
      phenomenon, arthritis, and Hashimoto's thyroiditis. Information is sparse
      regarding the prevalence and natural history of these conditions when associated
      with primary biliary cirrhosis and their response to ursodeoxycholic acid
      treatment. We evaluated the prevalence, natural history, and response to
      ursodeoxycholic acid therapy of these conditions coassociated with primary
      biliary cirrhosis. METHODS: One hundred-eighty patients with primary biliary
      cirrhosis, enrolled in a prospective randomized controlled trial of
      ursodeoxycholic acid (13-15 mg/ kg/day), were included. Patients were assessed at
      study entry and annually. RESULTS: At entry, 77/180 patients (43%) had one of the
      four conditions, and 18/180 patients (10%) had two or more conditions. Sicca
      syndrome was the most common, occurring in 58/180 patients (32%). After 2 yr,
      there was no difference between the treatment groups with regard to resolution or
      spontaneous onset of these autoimmune features. Sicca syndrome was the most
      common spontaneously developing condition (9% per yr). Sicca syndrome was the
      most common associated autoimmune condition, present in one-third of our
      patients. The associated conditions tended to improve over time, with a low rate
      of spontaneously developing these conditions. Although ursodeoxycholic acid
      therapy leads to improvement in the underlying liver disease, it did not appear
      to influence either the development or resolution of these autoimmune features.
      CONCLUSIONS: Although ursodeoxycholic acid is beneficial in the treatment of
      primary biliary cirrhosis, it had no measurable effect on the autoimmune
      conditions coassociated with the disease.

PMID- 9647029
TI  - The effect of ciprofloxacin in the prevention of bacterial infection in patients
      with cirrhosis after upper gastrointestinal bleeding.
AB  - OBJECTIVES: Cirrhotic patients with upper gastrointestinal bleeding are prone to
      bacterial infection. The aim of this study was to investigate the efficacy of
      prophylactic intestinal decontamination with oral ciprofloxacin for the
      prevention of bacterial infections in cirrhotic patients with upper
      gastrointestinal bleeding. METHODS: A total of 120 cirrhotic patients with acute
      upper gastrointestinal bleeding were enrolled. Sixty patients received
      ciprofloxacin 500 mg twice daily given orally or through nasogastric tube
      immediately after upper gastrointestinal endoscopic examination; drug
      administration continued for 7 days. The remaining 60 patients, who received
      placebo, served as controls. RESULTS: The incidence of proven bacterial infection
      in the ciprofloxacin-treated group was significantly lower than that of placebo
      group (10% vs 45%, p < 0.001). The incidences of bacteremia, spontaneous
      bacterial peritonitis, and urinary tract infection in the ciprofloxacin-treated
      group were significantly lower than those in the placebo group (0% vs 23%, 3.3%
      vs 13%, and 5% vs 18%, respectively; p < 0.05, respectively). Multivariate
      logistic regression analysis showed that a lack of prophylactic treatment with
      ciprofloxacin and severity of cirrhosis were the independent significant
      predictors for cirrhotic patients with acute gastrointestinal bleeding with
      infection. CONCLUSIONS: Prophylactic intestinal decontamination with oral
      ciprofloxacin is effective in the prevention of bacterial infections in patients
      with cirrhosis who were suffering from acute upper gastrointestinal hemorrhage.

PMID- 9647030
TI  - Beneficial effect of a bile acid resin binder on enteral feeding induced
      diarrhea.
AB  - OBJECTIVES: Diarrhea is a complication of enteral feeding, occurring in up to 68%
      of critically ill patients. We hypothesized that prolonged fasting results in
      abnormal bile acid homeostasis. Subsequent enteral feeding then causes a relative
      luminal excess of bile acids, which leads to choleretic diarrhea. Hence, diarrhea
      induced by enteral feeding should improve with the use of a bile acid binding
      agent, such as Colestid Granules. METHODS: We evaluated the effect of Colestid on
      enteral feeding-induced diarrhea in a double-blind placebo-controlled study.
      Nineteen patients who were nil per os (NPO) for 5 days before initiation of
      enteral feeding were enrolled in the study and treatment continued for 7 days.
      The severity and frequency of diarrhea were quantified. Fecal bile acids were
      measured enzymatically. Stool nutrient loss was measured by fat extraction,
      microkjeldahl determination of nitrogen, and bomb calorimetry of dried fecal
      specimens. RESULTS: Enteral feeding resulted in a high frequency of diarrhea
      (95%) at some time during the observation period. The majority of episodes of
      diarrhea in both groups were of low volume. Colestid significantly decreased the
      prevalence and severity of diarrhea. Colestid had no significant effect on fecal
      calorie or nutrient losses. The average bile acid concentration in the stool
      increased significantly after enteral feeding. CONCLUSION: Enteral feeding
      induced diarrhea is, at least in part, due to malabsorption of bile acids. The
      bile acid resin binding agent Colestid improves diarrhea induced by enteral
      feeding.

PMID- 9647031
TI  - A double-blind placebo-controlled pilot study of glutamine therapy for abnormal
      intestinal permeability in patients with AIDS.
AB  - OBJECTIVES: Up to 20% of patients with AIDS have abnormal intestinal permeability
      (IP). Glutamine seems to play an important role in preventing the increase in IP
      and loss of intestinal mucosal mass associated with total parenteral nutrition,
      and may be superior to glucose for oral rehydration in the setting of intestinal
      infection. This study was designed to see if supplemental glutamine could alter
      the abnormal IP of AIDS. METHODS: Randomly chosen patients with AIDS from the
      Jacobi Medical Center human immunodeficiency virus (HIV) clinic underwent IP
      testing using lactulose and mannitol. Those with abnormal IP were enrolled.
      Duodenal biopsies were performed with a Crosby capsule and the patients were
      randomized in a double-blind fashion to receive placebo or glutamine (4 g/day or
      8 g/day) for 28 days, after which intestinal permeability tests and duodenal
      biopsies were repeated. Intestinal morphology was graded by ratio of villus
      height to crypt depth, and by degree of inflammation. RESULTS: All patients
      complied with the therapy and there were no dropouts or reported side effects.
      The results showed less worsening of IP with the 4 g/day dose, compared with
      placebo. At the 8 g/day dose, there was stabilization of IP and improved
      absorption of mannitol. Intestinal morphology and inflammation did not change in
      any group. CONCLUSIONS: These results, although not significant, suggest a trend
      towards improved IP and enhanced intestinal absorption with glutamine. Glutamine
      doses of at least 20 g/day may be necessary to improve IP. We recommend further
      studies at higher doses and for longer durations.

PMID- 9647032
TI  - Thyroid and celiac disease: clinical, serological, and echographic study.
AB  - OBJECTIVE: We sought to reevaluate the prevalence of thyroid dysfunction and
      thyroid autoimmunity in 47 patients with celiac disease; 91 healthy subjects were
      studied as controls. Both patients and controls were from Sardinia, Italy.
      METHODS: Diagnosis of celiac disease was made on the basis of clinical history,
      presence of positive antigliadin IgA (AGA-A) and IgG (AGA-G) antibodies,
      antireticulin antibodies (ARA), antiendomysium antibodies (EMA), and was
      confirmed by jejunal biopsy. HLA class II typing for DQB1 and DQA1 alleles was
      performed in 36/47 celiac patients. Thyroid was evaluated by palpation and
      echography; serum free thyroid hormones (FT4, FT3), thyrotropic hormone (TSH),
      and antithyroid peroxidase autoantibodies (anti-TPO) were assayed by
      radioimmunoassays. RESULTS: The prevalence of anti-TPO was higher in celiac
      patients (29.7%) than in healthy controls (9.6%) (p < 0.001) and thyroid
      echography frequently displayed (42.5%) a hypoechogenic pattern. Five anti-TPO
      positive celiac patients were hypothyroid (two overt, three subclinical). A
      higher but not significantly different prevalence of anti-TPO (3/7 = 42.8%) was
      found in celiac patients displaying the DQB1*0502 genotype, when compared with
      the remaining patients (8/29 = 27.6%). CONCLUSIONS: An elevated prevalence of
      clinical and subclinical autoimmune thyroid autoimmunity was found in Sardinian
      celiac patients, especially in those displaying the DQB1*0502 genotype; this
      finding could be related to a particular genetic background of the Sardinian
      population.

PMID- 9647033
TI  - P53 protein immunohistochemical expression in colonic adenomas with and without
      associated carcinoma.
AB  - OBJECTIVES: P53 protein immunohistochemical (IHC) expression was investigated in
      a series of colonic adenomas and carcinomas to determine the p53
      immunohistochemical expression of adenomas in general compared with carcinomas,
      the difference in staining pattern between adenomas with associated carcinoma and
      those without associated carcinoma, and the difference in p53 staining in the
      usual adenomas (low-grade dysplasia) compared with those harboring high-grade
      dysplasia. METHODS: The study involved a series of 20 adenomas without concurrent
      carcinoma (group 1 adenoma), 29 adenomas with concurrent carcinoma (group 2
      adenoma), and 20 carcinomas. Sections of the paraffin-embedded tissues were
      stained with DO-7 p53 monoclonal antibody after microwave antigen-retrieval
      method. Cases with nuclear staining in > or = 20% of the tumor cells were
      considered positive. RESULTS: Analysis of results showed that 65% of carcinomas
      and 37% of all adenomas were reactive with p53 IHC staining (p = 0.03). With
      respect to the adenomas, 30% of group 1 and 41% of group 2 adenomas were reactive
      for p53 protein (p = 0.42). CONCLUSIONS: Our data demonstrate a statistically
      significant higher p53 expression rate in colonic carcinomas than in adenomas,
      and that adenomas with concurrent carcinomas are more frequently p53 positive
      than those without concurrent carcinoma, but this was not statistically
      significant. Also, p53 expression is more frequent and intense in adenomas with
      high-grade dysplasia (10/20, 50%) than in ordinary adenomas with low-grade
      dysplasia (8/29, 28%), which suggests a strong correlation between the degree of
      dysplasia in colonic neoplasia and p53 expression pattern.

PMID- 9647034
TI  - Psychological and physical stress induce differential effects on human colonic
      motility.
AB  - OBJECTIVE: Stress modulates gut function, but whether the type of stressor
      influences colonic motor activity is unclear. The motor patterns and regional
      variations are also poorly understood. Our aim was to determine the effects of
      psychological and physical stress on colonic motility. METHODS: Ambulatory
      colonic manometry was performed by placing a six-sensor probe up to the mid
      transverse colon, without sedation, in 12 healthy subjects. Five hours later, a
      dichotomous listening test (psychological stress) was performed, which was
      preceded by listening to a narrative passage (control); recovery entailed
      listening to relaxing music (1 h each). Subsequently, intermittent hand immersion
      in cold (4 degrees C) water (physical stress) was performed, preceded by hand
      immersion in warm (37 degrees C) water (1/2-h each). Colonic pressure activity
      and cardiovascular responses were measured throughout the study. RESULTS: When
      compared with the control period, both stressors induced a greater number of
      pressure waves (p < 0.05), and the area under the curve (p < 0.01), but only
      physical stress increased (p < 0.05) pulse rate and blood pressure. There were no
      regional differences in colonic motility. During recovery, the motor activity
      returned to baseline after physical stress, but remained high after psychological
      stress. Psychological stress induced more (p < 0.05) propagated contractions,
      whereas physical stress induced more (p < 0.05) simultaneous contractions.
      CONCLUSIONS: Both stressors enhanced colonic motor activity, but psychological
      stress induced a prolonged response with propagated activity and without
      appreciable autonomic response. Thus, colonic motor responses may vary depending
      on the stressor.

PMID- 9647035
TI  - Palliation of obstructing gastric carcinoma with metal stents through a
      gastrostomy.
AB  - Gastric cancer is the world's second most common malignancy. In the U.S.,
      patients present with advanced disease, and surgery with curative intent accounts
      for only 30% of gastric malignancies. Palliative surgery has significant
      morbidity and mortality. Recently, there have been encouraging reports of self
      expanding endoprostheses in obstructing gastrointestinal neoplasms. We report a
      case of a 70-yr-old woman with inoperable outlet stenosis secondary to a mucinous
      infiltrating adenocarcinoma involving nearly the entire stomach, except the
      anterior wall, which provided a percutaneous access site for gastrostomy and
      subsequently successful management of outlet obstruction with metallic stents.

PMID- 9647036
TI  - Pseudogastroparesis as a presentation of adenocarcinoma of the proximal jejunum.
AB  - Establishing the presence of adenocarcinoma of the small bowel is exceedingly
      difficult. Survival is contingent on prompt diagnosis. We describe a patient with
      an atypical presentation of jejunal adenocarcinoma visualized via small bowel
      enteroclysis. She was referred with "gastroparesis," based on both a
      radionucleotide scan that revealed markedly delayed gastric emptying and a
      "normal" small bowel series. A markedly abnormal scintigraphic study and a
      negative small bowel series does not exclude disease of the small intestine and
      should provide the impetus to further pursue the possibility of an obstructing
      lesion. The enteroclysis is a relatively safe and effective study in the
      preoperative diagnosis of small bowel tumors.

PMID- 9647037
TI  - Hepatoma with severe non-islet cell tumor hypoglycemia.
AB  - We report a 22-yr-old male patient with chronic hepatitis B and a large, well
      differentiated hepatoma who developed episodes of symptomatic fasting
      hypoglycemia, which were caused by paraneoplastic secretion of unprocessed "big"
      insulin-like growth factor-II. Initially, the patient presented with normal liver
      function, which deteriorated during the clinical course. Therapeutic attempts to
      reduce tumor mass failed and the patient subsequently died because of metastases
      of the hepatoma. The pathophysiology of non-islet cell tumor hypoglycemia,
      differential diagnosis, and therapeutic options are discussed.

PMID- 9647038
TI  - Typhoid fever complicated by acute renal failure and hepatitis: case reports and
      review.
AB  - Four cases of typhoid fever complicated by both acute oliguric renal failure and
      hepatitis are presented. Two patients had type II hepatitis according to criteria
      proposed by Khosla et al. (30) with hepatomegaly, hyperbilirubinaemia and
      markedly elevated asparate transaminase (AST); the others had type III hepatitis,
      characterized clinically and biochemically by profound jaundice, hepatomegaly,
      hepatic encephalopathy (one case only), hyperbilirubinemia and markedly elevated
      serum AST. Renal biopsy was not performed in any of our patients. However, a
      combination of proteinuria and abnormal urinary sediments containing red cell
      casts and granular casts, as noted in these patients, is considered highly
      suggestive of glomerulonephritis. Although isolated renal failure and hepatitis
      with hepatomegaly and deranged liver enzyme values have been reported previously
      in typhoid fever, their occurrence simultaneously in the same patient in
      distinctly rare, having been reported only twice in the English language
      literature.

PMID- 9647039
TI  - Gastric angiomyolipoma: a previously undescribed cause of upper GI hemorrhage.
AB  - Angiomyolipomas are rare lesions often arising in the kidney. We describe the
      first documented case of symptomatic gastric angiomyolipoma.

PMID- 9647040
TI  - Transient protein-losing enteropathy associated with cytomegalovirus infection in
      a noncompromised host: a case report.

PMID- 9647041
TI  - Gastroesophageal reflux--is it hereditary?

PMID- 9647042
TI  - Surgical and medical therapies for GERD--can we see into the future?

PMID- 9647043
TI  - Endoscopic ultrasound, ampullary tumors, and minimally invasive therapy: a cost
      saving combination?

PMID- 9647044
TI  - Polymyositis and esophageal carcinoma.

PMID- 9647045
TI  - Vertical transmission of Helicobacter pylori: different transmission route.

PMID- 9647046
TI  - Botulinum toxin injection in achalasia before myotomy.

PMID- 9647047
TI  - Aeromonas as a cause of segmental colitis.

PMID- 9647048
TI  - Severe leukocytosis with neutrophilia (leukemoid reaction) in alcoholic
      steatohepatitis.

PMID- 9647049
TI  - Cutaneous vasculitis as the initial manifestation of Crohn's disease in a
      pediatric patient.

PMID- 9647050
TI  - Colon cancer in young persons of East African descent.

PMID- 9647051
TI  - Long-term clinical outcome after transcervical thymectomy for myasthenia gravis.
AB  - BACKGROUND: We reviewed the long-term clinical outcome after transcervical
      thymectomy for generalized myasthenia gravis without thymoma in 52 patients who
      had this procedure at The Toronto Hospital between 1977 and 1986, and compared
      the results with those reported after more radical surgical approaches. METHODS:
      Preoperative and postoperative patient evaluations were based on a modified
      Osserman classification. We defined complete remission as asymptomatic with
      normal strength and without medications for myasthenia gravis. The complete
      remission rate was selected as the best measure for comparison between different
      surgical approaches. RESULTS: The 52 patients were followed up for a mean of 8.4
      years (+/-6.1 years [standard deviation]). The preoperative mean Osserman grade
      was 2.7 compared with 0.4 at final follow-up. Complete remission occurred in
      44.2% of patients. Similar results are reported after transsternal thymectomy.
      CONCLUSIONS: Comparable results after transcervical and transsternal thymectomy
      favor the use of the less radical approach.

PMID- 9647052
TI  - Cytostatic lung perfusion by use of an endovascular blood flow occlusion
      technique.
AB  - BACKGROUND: Different modalities of cytostatic lung perfusion were compared
      regarding plasma and tissue drug concentrations to assess the efficacy of an
      endovascular blood flow occlusion technique. METHODS: A cytostatic lung perfusion
      study with doxorubicin hydrochloride was performed on large white pigs (n = 12).
      Plasma and tissue concentrations of doxorubicin were compared for isolated lung
      perfusion with open cannulation (ILP), blood flow occlusion perfusion with open
      cannulation of the pulmonary artery alone (BFO), and intravenous drug
      administration (i.v.). In a fourth group, thoracotomy-free BFO perfusion was
      performed by endovascular balloon catheterization of the pulmonary artery
      (endovascular BFO). The 3 animals in this group were used to compare the
      doxorubicin-perfused pulmonary tissue with the contralateral nonperfused lobes
      after 1 month. RESULTS: The mean lung tissue doxorubicin concentration at the end
      of perfusion was 19.8 +/- 1.6 microg/g after ILP, 27.6 +/- 2.2 microg/g after BFO
      (p = not significant), and 3.0 +/- 0.8 microg/g after i.v. perfusion (p < 0.01).
      Whereas doxorubicin was not detectable in the plasma in the ILP group,
      concentrations ranged from not detectable to 0.44 microg/mL in the BFO group and
      from 0.31 to 0.84 microg/mL in the i.v. group (p < 0.05). Mean myocardial tissue
      concentration was not significantly different after BFO than i.v. perfusion (1.1
      +/- 0.5 microg/g and 1.8 +/- 0.1 microg/g, respectively). In the endovascular BFO
      group, balloon-blocked pulmonary artery perfusion was successfully performed in
      all animals, and after 1 month, lung tissue showed no cytostatic-induced
      histologic changes. CONCLUSIONS: Compared with ILP, BFO cytostatic lung perfusion
      produced an insignificantly higher lung-tissue concentration, corresponding to a
      sixfold to ninefold higher level than after i.v. perfusion. Plasma drug levels
      during BFO perfusion were lower than during i.v. perfusion. Endovascular BFO may
      be a promising technique for repeated cytostatic lung perfusion.

PMID- 9647053
TI  - Multiple primary cancers in esophageal squamous cell carcinoma: incidence and
      implications.
AB  - BACKGROUND: The occurrence of multiple primary cancers in the aerodigestive tract
      is a well-known phenomenon. This study aims to elucidate the incidence and the
      therapeutic and prognostic implications of a nonesophageal primary cancer in
      patients with squamous cell carcinoma of the esophagus. METHODS: Between 1982 and
      1996, 1,055 patients with esophageal squamous cell carcinoma treated at our
      institution were reviewed for the presence of an additional primary cancer. The
      effects of the nonesophageal cancer on treatment of the esophageal carcinoma and
      survival were analyzed. RESULTS: Among 1,055 patients, 114 nonesophageal primary
      cancers were documented in 100 patients (9.5%), 70% of which were aerodigestive
      tract cancers. Forty-seven patients had antecedent tumors and 43 had synchronous
      tumors. Treatment strategies for esophageal carcinoma in these patients were
      similar to patients without multiple tumors, not influenced by the nonesophageal
      tumor except in 6 patients. The overall survival of patients with antecedent
      tumors, synchronous tumors, and without multiple tumors was similar (median
      survival, 8.6, 8.5, and 8.8 months, respectively) (p = 0.84). Subsequent primary
      cancers developed in 10 patients (0.9%), 9 of them with previous curative
      resection of esophageal cancer, and all died of the subsequent cancer.
      CONCLUSIONS: There is a high incidence of multiple primary cancers in patients
      with esophageal carcinoma but the treatment and prognosis of these patients are
      primarily determined by the esophageal carcinoma itself. Subsequent cancer is,
      however, a significant cause of death among patients cured of esophageal
      carcinoma.

PMID- 9647054
TI  - Minimally invasive valve operations.
AB  - BACKGROUND: To reduce the morbidity from valvular heart operations, a right
      parasternal approach was introduced. We report our initial experience with the
      procedure. METHODS: From January 1996 through July 1996, 115 patients underwent
      primary isolated valve procedures. One hundred (85%) patients underwent the
      operation through a right parasternal incision. RESULTS: There was one hospital
      death secondary to a stroke on the fifth postoperative day. Three patients (two
      with aortic valve operations and one having a mitral valve procedure) required
      conversion to sternotomy. Mean aortic occlusion time was 71 minutes; mean
      cardiopulmonary bypass time was 93 minutes. Mean stay in the intensive care unit
      was 27 hours and mean hospital postoperative stay was 5.7 days. Seventy-seven
      percent of the patients did not receive blood transfusions. Comparison with
      median sternotomy demonstrated a reduction in both postoperative length of stay
      and direct hospital costs. CONCLUSIONS: We conclude that this minimally invasive
      approach is safe for a variety of valve procedures and is effective in reducing
      surgical trauma and cost.

PMID- 9647055
TI  - Therapeutic angiogenesis with basic fibroblast growth factor: technique and early
      results.
AB  - BACKGROUND: Patients not amenable to complete myocardial revascularization by
      conventional methods present a difficult clinical problem. Here we present the
      early results and technical considerations of the administration of basic
      fibroblast growth factor for the induction of collateral growth using heparin
      alginate slow-release devices in patients undergoing coronary artery bypass
      grafting. METHODS: Eight patients were enrolled. Patients were candidates if they
      had at least one graftable obstructed coronary artery and at least one major
      arterial distribution not amenable to revascularization, a serum creatinine level
      less than 3 mg/dL, ejection fraction greater than 0.20, and estimated operative
      mortality of less than 25%. During conventional coronary artery bypass grafting,
      10 heparin-alginate devices, each containing either 1 microg or 10 microg of
      basic fibroblast growth factor, were implanted in the epicardial fat in multiple
      regions of the unrevascularizable territory and also in the distal distribution
      of a grafted or patent artery. RESULTS: There was no mortality and no evidence of
      renal, hematologic, or hepatic toxicity during follow-up. Three months after the
      operation, all patients remain free of angina. Seven patients were examined with
      stress perfusion scans. Three patients had clear enhancement of perfusion to the
      unrevascularized myocardium, 1 patient had a new fixed defect, and 3 had minimal
      overall change but had evidence of new small, fixed perfusion defects. Seven
      patients had improved or similar myocardial contractile function (ejection
      fraction at 3-month follow-up = 0.53 +/- 0.22 versus 0.47 +/- 0.14
      preoperatively). One patient suffered a perioperative myocardial infarction in
      the area of basic fibroblast growth factor administration. CONCLUSIONS: This
      preliminary study demonstrates the safety and technical feasibility of
      therapeutic angiogenesis with basic fibroblast growth factor delivered by heparin
      alginate slow-release devices. Further studies examining the safety, clinical
      efficacy, and long-term results are ongoing.

PMID- 9647056
TI  - Risk of reoperative valve replacement for failed mitral and aortic bioprostheses.
AB  - BACKGROUND: One factor influencing the choice of mechanical versus bioprosthetic
      valves is reoperation for bioprosthetic valve failure. To define its operative
      risk, we reviewed our results with valve reoperation for bioprosthetic valve
      failure. METHODS: Records of 400 consecutive patients having reoperative mitral,
      aortic, or mitral and aortic bioprosthetic valve replacement from January 1985 to
      March 1997 were reviewed. RESULTS: Reoperations were for failed bioprosthetic
      mitral valves in 219 patients, failed aortic valves in 153 patients, and failed
      aortic and mitral valves in 28 patients. Including 26 operations (6%) for acute
      endocarditis, 153 operations (38%) were nonelective. One hundred nine patients
      (27%) had other valves repaired or replaced, and 72 (18%) had coronary bypass
      grafting. The incidence of death in the mitral, aortic, and double-valve groups
      was respectively, 15 (6.8%), 12 (7.8%), and 4 (14.3%); and the incidence of
      prolonged postoperative hospital stay (>14 days) was, respectively, 57 (26.0%),
      41 (26.8%), and 8 (28.6%). Only 7 of 147 patients (4.8%) having elective,
      isolated, first-time valve reoperation died. Multivariable predictors (p < 0.05)
      of hospital death were age greater than 65 years, male sex, renal insufficiency,
      and nonelective operation; and predictors of prolonged stay were acute
      endocarditis, renal insufficiency, any concurrent cardiac operation, and elevated
      pulmonary artery systolic pressure. CONCLUSIONS: Reoperative bioprosthetic valve
      replacement can be performed with acceptable mortality and hospital stay. The
      best results are achieved with elective valve replacement, without concurrent
      cardiac procedures.

PMID- 9647057
TI  - The Ross procedure: shorter hospital stay, decreased morbidity, and cost
      effective.
AB  - BACKGROUND: The Ross procedure has become an accepted and sometimes preferred
      alternative to mechanical aortic valve replacement. One criticism of the Ross
      procedure is that it may have a higher operative mortality, morbidity, and cost.
      Several groups have shown that this operation can be performed safely with less
      than 3% mortality. The issue of higher cost has not been resolved. In this
      retrospective study we compared a consecutive group of patients undergoing the
      Ross procedure with an age- and disease-matched group of patients who underwent
      mechanical aortic valve replacement. METHODS: From 1993 to 1996, 22 consecutive
      adult patients (age range, 20 to 57 years; mean, 38 +/- 14 years) underwent the
      Ross procedure. Twenty-seven patients (age range, 17 to 57 years; mean, 41 +/- 10
      years) underwent mechanical aortic valve replacement between 1991 and 1996. The
      hospital cost (in 1996 dollars) and postoperative length of stay were calculated
      for each patient using Transition I, a hospital-wide cost accounting system.
      RESULTS: There was no hospital mortality in either group. The incidence of
      significant valve-related complication was 5% (1/22 patients) in the Ross
      procedure group and 22% (6/27 patients) in the mechanical valve group. There were
      two late deaths in the group with mechanical aortic valve replacement. The length
      of stay for the Ross procedure group was 5.9 +/- 2.1 days, versus 8 +/- 1.85 days
      for the mechanical valve group (p < 0.01). The mean hospital costs were not
      significantly different, $23,140 +/- $7,825 for the mechanical valve group and
      $23,226 +/- $6,960 for the group having the Ross procedure. CONCLUSIONS: The data
      from this review demonstrate that the Ross procedure can be done safely, with
      short hospital stays, decreased morbidity, and costs comparable with those of
      standard mechanical aortic valve replacement in patients with isolated aortic
      valve disease.

PMID- 9647058
TI  - Intermittent antegrade tepid versus cold blood cardioplegia in elective
      myocardial revascularization.
AB  - BACKGROUND: The ideal temperature for blood cardioplegia administration remains
      controversial. METHODS: Fifty-two patients who required elective myocardial
      revascularization were prospectively randomized to receive intermittent antegrade
      tepid (29 degrees C; group T, 25 patients) or cold (4 degrees C; group C, 27
      patients) blood cardioplegia. RESULTS: The two cohorts were similar with respect
      to all preoperative and intraoperative variables. The mean septal temperature was
      higher in group T (T, 29.6 degrees +/- 1.1 degrees C versus 17.5 degrees +/- 3.0
      degrees C; p < 0.0001). After reperfusion, group T exhibited significantly
      greater lactate and acid release despite similar levels of oxygen extraction (p <
      0.05). The creatine kinase-MB isoenzyme release was significantly lower in group
      T (764 +/- 89 versus 1,120 +/- 141 U x h/L; p < 0.04). Hearts protected with
      tepid cardioplegia demonstrated significantly increased ejection fraction with
      volume loading, improvement in left ventricular function at 12 hours, and
      decreased need for postoperative inotropic support (p < 0.05). The frequency of
      ventricular defibrillation after cross-clamp removal was lower in this cohort (p
      < 0.05). There were no hospital deaths, and both groups had similar postoperative
      courses. CONCLUSIONS: Intermittent antegrade tepid blood cardioplegia is a safe
      and efficacious method of myocardial protection and demonstrates advantages when
      compared with cold blood cardioplegia in elective myocardial revascularization.

PMID- 9647059
TI  - Is atrial fibrillation resulting from rheumatic mitral valve disease a proper
      indication for the maze procedure?
AB  - BACKGROUND: There are a few patients without detectable atrial contraction
      despite restoration of atrial rhythm after the maze procedure for atrial
      fibrillation (AF) associated with mitral valve disease. METHODS: From January
      1995 to March 1997, 29 consecutive patients with AF associated with mitral valve
      disease underwent our modified maze procedure combined with mitral or other valve
      operations. The causes of mitral valve disease were rheumatic mitral stenosis (n
      = 22) and nonrheumatic mitral regurgitation (n = 7). The 17 patients with
      postoperative atrial rhythm were divided into group I with rheumatic mitral
      stenosis (n = 10), and group II with mitral regurgitation of nonrheumatic origins
      (n = 7). RESULTS: Seventeen patients regained atrial rhythm, 2 patients had
      junctional rhythm, and another 10 remained in AF. Between the group of patients
      with restoration of atrial rhythm and that of patients remaining in AF,
      significant differences were found in the percentage with rheumatic disease,
      history of AF, and maximum f-wave voltage. The postoperative peak velocity of the
      atrial filling wave to peak velocity of early filling wave ratio for the left
      atrium measured using Doppler echocardiography was 0.25 in group I, which was
      significantly lower than that (0.42) in group II. CONCLUSIONS: Reconsideration of
      the indications for the maze procedure for AF associated with rheumatic mitral
      stenosis may thus be reasonable, particularly for cases in which replacement
      using a prosthetic valve is necessary, but we believe that patients with
      nonrheumatic mitral valve disease, especially those able to undergo
      reconstructive operations, are the best candidates for the maze procedure.

PMID- 9647060
TI  - Lethal postoperative coronary artery spasm.
AB  - BACKGROUND: Coronary artery spasm in the immediate postoperative period after a
      coronary operation is recognized infrequently. Its severity is variable and
      manifestations unpredictable. The diagnosis is usually made by an awareness of
      the possibility and thereafter by exclusion of other causes of myocardial
      ischemia. An opportunity for a positive diagnosis is rarely available. METHODS:
      The case reports of 3 patients with similar presentations of ischemic heart
      disease and with severe manifestations of coronary artery spasm in the
      postoperative period are presented. RESULTS: All 3 patients were women aged 55 to
      60 years. All had single-vessel coronary artery disease involving the left
      anterior descending artery and underwent a left internal mammary artery bypass
      graft. Severe manifestations of myocardial ischemia of abrupt onset developed
      approximately 7 hours postoperatively in each patient. One patient died of severe
      hemodynamic deterioration from which resuscitation was unsuccessful. Another
      sustained a large anterior myocardial infarction despite graft patency. The third
      patient was supported by an intraaortic balloon pump and made a full recovery.
      CONCLUSIONS: The early diagnosis of coronary artery spasm is achieved by an
      awareness of the condition. The institution of early appropriate management may
      prevent its consequences.

PMID- 9647061
TI  - Risk factors for death after heart transplantation: does a single-center
      experience correlate with multicenter registries?
AB  - BACKGROUND: Risk factors for death after heart transplantation (Tx) are
      frequently documented from multicenter registries. Although this information is
      helpful, it reflects a whole range of experiences and results, and may not
      translate to a particular center. This study was performed to (1) evaluate pre-Tx
      factors affecting mortality in a single-center experience, and (2) compare these
      factors with risk factors obtained from multicenter registry reports. METHODS:
      Review of our transplant database between January 1984 and December 1995
      identified 405 adults who received a primary heart Tx. Multiple factors were
      analyzed, including demographics, Tx era, cytomegalovirus status, United Network
      for Organ Sharing status of recipient, presence of pulmonary hypertension,
      previous cardiac operations, mechanical ventilation or circulatory support,
      ischemia time, number of rejection episodes, and preoperative flow cytometry
      crossmatching. RESULTS: One- and 5-year survival rates were 87.8% and 73.4%,
      respectively (Kaplan-Meier). Contrary to multicenter registry reports, our data
      indicate that reoperative procedures, left ventricular assist device support,
      increasing donor and recipient age, and ischemia time up to 4.2 hours are not
      risk factors for death after Tx. Likewise, mode of donor death is not a risk
      factor affecting outcome. Significant risk factors for mortality identified by
      multivariate analysis included early transplant era (1984 to 1989; p = 0.002),
      female donor (p = 0.042), cytomegalovirus-seropositive donor (p = 0.048), high
      pulmonary vascular resistance (p = 0.018), and intraaortic balloon pump support
      (p = 0.03). It also identified a positive B-cell flow cytometry crossmatch (p =
      0.015) to be a risk factor with univariate analysis. CONCLUSIONS: Our data
      identify a group of recipients, reportedly at high risk in multicenter
      registries, who are not at increased risk of death after Tx. This information
      supports the growing experience with older donors and recipients and with bridged
      transplants, and has allowed us to expand our donor pool. These prognostic
      factors at evaluation allow more liberal selection of patients and donors for
      transplantation.

PMID- 9647062
TI  - Terminal warm blood cardioplegia improves cardiac function through microtubule
      repolymerization.
AB  - BACKGROUND: To elucidate the mechanisms responsible for the beneficial effects of
      terminal warm blood cardioplegia, we studied dynamic change in microtubules
      induced by cold cardioplegia followed by rewarming. Further, we investigated the
      relationship between cardiac function and morphologic changes in microtubules
      caused by hyperkalemic, hypocalcemic warm cardioplegia during initial
      reperfusion. METHODS: In protocol 1 isolated rat hearts were perfused at 37
      degrees C with Krebs-Henseleit buffer (KHB). After 3 hours of hypothermic cardiac
      arrest at 10 degrees C, hearts were reperfused at 37 degrees C with one of two
      buffers: group C, 60-minute reperfusion with KHB (K+, 5.9 mmol/L; Ca2+, 2.5
      mmol/L); and group TC, 10-minute initial reperfusion with modified KHB (K+, 15
      mmol/L; Ca2+, 0.25 mmol/L), followed by 50 minutes of reperfusion with KHB.
      Cardiac function after reperfusion was determined as a percentage of the
      prearrest value. In protocol 2 hearts were perfused at 37 degrees C with KHB
      containing colchicine (10(-5) mol/L) for 60 minutes. RESULTS: There was
      spontaneous contractile recovery after 10 minutes of initial reperfusion in
      hearts from group TC as well as improved cardiac function after 15, 30, and 60
      minutes of reperfusion compared with that in group C. Immunohistochemical
      staining and immunoblot analysis demonstrated microtubule depolymerization during
      hypothermic cardiac arrest and complete repolymerization after 10 minutes of
      reperfusion with warm buffers in both groups. Colchicine-induced microtubule
      depolymerization is associated with deterioration of cardiac function.
      CONCLUSIONS: One mechanism responsible for improved cardiac function mediated by
      terminal warm blood cardioplegia is the restart of contraction after complete
      microtubule repolymerization.

PMID- 9647063
TI  - Hyperglycemia during normothermic cardiopulmonary bypass: the role of the kidney.
AB  - BACKGROUND: Hyperglycemia commonly occurs during cardiopulmonary bypass. We
      studied the quantitative impact of glucose input and its renal excretion on
      hyperglycemia during cardiopulmonary bypass. METHODS: The quantity of glucose
      infused and metabolite and hormone concentrations in plasma, as well as oxygen
      consumption, carbon dioxide production, and renal glucose excretion, were
      determined before, during, and after cardiopulmonary bypass in 8 patients.
      RESULTS: Hyperglycemia (14 to 29 mmol/L) was accompanied by an increase in plasma
      insulin levels. The degree of hyperglycemia was directly related to the amount of
      glucose infused. The rate of oxygen consumption did not decrease and the rate of
      urea appearance (gluconeogenesis) did not rise. Despite a very high filtered load
      of glucose, there was very little glucosuria, indicating a markedly enhanced
      renal absorption of glucose. CONCLUSIONS: Hormonal and metabolic factors permit
      the development of hyperglycemia during cardiopulmonary bypass but its severity
      depends on the quantity of glucose infused and, what appears to be a new finding,
      a markedly enhanced renal reabsorption of filtered glucose. Thus the kidney plays
      an important role in the development of severe hyperglycemia during
      cardiopulmonary bypass.

PMID- 9647064
TI  - Left main coronary artery patch angioplasty: midterm experience and follow-up
      with spiral computed tomography.
AB  - BACKGROUND: Patch angioplasty is an alternative surgical technique in cases of
      left main coronary artery stenosis. We report our experience with this technique,
      with particular mention of the use of spiral computed tomography for the follow
      up of our patients. METHODS: In this retrospective study we analyzed the results
      obtained in all 7 patients (3 women and 4 men) who were operated on with this
      technique in our institution between July 1992 and August 1994. Five consenting
      patients also underwent graft patency assessment with spiral computed tomographic
      imaging. RESULTS: The operation was uneventful in all patients and there were no
      hospital deaths. Two patients required reoperation (1 of them dying at
      reoperation), 1 because of restenosis of the graft and 1 because of the presence
      of a new stenosis in the proximal anterior descending coronary artery. The
      remaining 5 patients were asymptomatic after 51 +/- 2 months. Spiral computed
      tomographic images were artifacted and of poor quality. CONCLUSIONS: Patch
      angioplasty of the left main coronary artery can be a valuable therapeutic method
      in selected cases. Conventional spiral computed tomography is not an optimal
      noninvasive method for the assessment of graft patency.

PMID- 9647065
TI  - Silent aspiration after coronary artery bypass grafting.
AB  - BACKGROUND: "Silent" aspiration was recognized to be a more frequent complication
      at this hospital in patients who have had coronary artery bypass grafting than in
      the general surgical population. METHODS: A case-control retrospective study
      covering a 4.5-year period was conducted to determine risk factors for pharyngeal
      dysfunction resulting in silent aspiration. RESULTS: Significant predictors of
      silent aspiration were age, history of cerebral vascular disease, insulin
      dependent diabetes mellitus, myocardial infarction, and chronic obstructive
      pulmonary disease. Intraaortic balloon pump and number of units of fresh-frozen
      plasma were the only independent intraoperative factors associated with silent
      aspiration in a model using continuous variables directly. Cold fibrillation was
      used in 7 of 53 study cases but no control patients, so it could not be modeled.
      Postoperative complications occurring with greater frequency included neurologic
      complications, adverse pulmonary outcomes, repeat surgical interventions,
      infection, and death. Using an Aspiration Risk Profile developed from the
      retrospective study, in a detailed prospective study of 10 patients, 3 of 4
      patients with postoperative dysphagia had objective evidence of stroke.
      CONCLUSIONS: These findings suggest that postoperative coronary artery bypass
      graft dysphagia may be the result of intraoperative cerebral injury, and that
      careful postoperative clinical evaluation of coronary artery bypass graft
      patients with risk factors may result in early diagnosis of pharyngeal
      dysfunction with the goals of preventing silent aspiration and reducing
      morbidity, mortality, and hospital cost.

PMID- 9647066
TI  - Apoptosis is involved in acute cardiac allograft rejection in rats.
AB  - BACKGROUND: Allograft rejection remains a major obstacle to long-term survival in
      heart transplantation. Recent studies have demonstrated that apoptotic cell death
      may occur in acute allograft rejection. The purpose of this study was to
      determine whether apoptotic cell death is involved in rat cardiac allograft
      rejection through both the perforin/granzyme pathway and the Fas/Fas ligand (Fas
      L) pathway. METHODS: Groups of Lewis (RT1(1)) rats underwent heterotopic heart
      transplantation from disparate DA (RT1a) or syngeneic Lewis rats. The cardiac
      grafts were harvested 1, 3, or 5 days after transplantation and analyzed for
      apoptotic cell death using DNA nick-end labeling, immunocytochemistry, and
      electron microscopy. In addition, the expression of granzyme B, perforin, Fas,
      and Fas-L messenger RNA were analyzed by reverse transcriptase-polymerase chain
      reaction. RESULTS: Apoptotic cell death of cardiac myocytes was prominent in
      allografts on day 5 after transplantation. Fas gene transcripts were
      constitutively expressed in both syngeneic and allogeneic grafts, whereas
      expression of Fas-L was only upregulated in allografts with ongoing rejection.
      Granzyme B and perforin gene expression were also upregulated in allografts with
      ongoing rejection. CONCLUSIONS: These results suggest that myocyte apoptosis
      through both the perforin-granzyme pathway and the Fas-Fas-L pathway may be
      involved in cardiac allograft rejection in rats.

PMID- 9647067
TI  - Myocardial distribution of antegrade cold crystalloid and tepid blood
      cardioplegia.
AB  - BACKGROUND: Tepid blood (TB) cardioplegia combines the improved rheologic
      characteristics and the augmented oxygen and substrate delivery of blood
      cardioplegia with the advantages of moderate hypothermia. In addition, the
      intramyocardial distribution of continuous TB cardioplegia may also be better
      than intermittent cold crystalloid (CC) cardioplegia. We sought to compare the
      distribution of TB and CC cardioplegia at varying infusion pressures. METHODS: In
      situ, isolated canine hearts were randomized to antegrade, continuous TB (28
      degrees C, n = 8) or intermittent CC (n = 8) cardioplegia infused at 50, 75, and
      100 mm Hg. The regional distribution of cardioplegia at each pressure was
      measured by 15-microm colored microspheres. Cardioplegia distribution was
      measured from three areas each of the right ventricle (inflow, outflow, and apex)
      and the left ventricle (anterior, lateral, and posterior). Left ventricular
      samples were subdivided into subepicardial, midmyocardial, and subendocardial.
      RESULTS: Delivery of cardioplegia to all areas of the right and left ventricles
      showed a linear pressure-flow relationship over the range of pressures tested.
      Right ventricular distribution was two-thirds of that to the left ventricle, and
      left ventricular subepicardial distribution was approximately one half of
      subendocardial flow in both groups at all delivery pressures. However, the
      subendocardial to subepicardial ratio was significantly greater with TB
      cardioplegia than with CC cardioplegia. Transmural right ventricular cardioplegia
      flow was comparable in both groups. In contrast, left ventricular distribution of
      CC cardioplegia was greater than TB cardioplegia at all three pressures tested.
      CONCLUSIONS: The pressure-flow relationship in both CC and TB cardioplegia is
      linear in both the right and left ventricular myocardium over clinically
      applicable delivery pressures. The distribution of cardioplegia to the right
      ventricle is not altered by increased pressure.

PMID- 9647068
TI  - Levels of troponin I and cardiac enzymes after reinfusion of shed blood in
      coronary operations.
AB  - BACKGROUND: Reinfusion of shed blood after coronary artery bypass grafting might
      increase the levels of cardiac enzymes with consequent difficulties in the
      diagnosis of perioperative myocardial infarction. METHODS: Thirty consecutive
      patients undergoing coronary artery bypass grafting who bled at least 400 mL
      within the first 4 hours after operation underwent reinfusion of shed blood.
      Thirty consecutive patients who were not autotransfused served as control. All
      patients underwent enzyme determination (total creatine kinase, MB fraction,
      lactate dehydrogenase, and troponin I) in the shed blood and in circulating blood
      preoperatively, at arrival in the intensive care unit, and 6, 24, and 48 hours
      after operation. RESULTS: The shed blood contained significantly higher
      concentration of cardiac enzymes than the circulating blood at all time intervals
      (p = 0.0001). The levels of creatine kinase, its MB fraction, and lactate
      dehydrogenase in circulating blood were significantly elevated in patients
      receiving autotransfusion up to 24 hours after autotransfusion. The blood levels
      of troponin I were not significantly different between the two group of patients
      at all time points. The percent fraction of MB did not increase after
      autotransfusion. CONCLUSIONS: The measurement of cardiac troponin I is a useful
      marker for the diagnosis of perioperative myocardial infarction in patients
      undergoing transfusion of shed blood after coronary operation.

PMID- 9647069
TI  - Atrial natriuretic peptide-induced release of cyclic guanosine monophosphate by
      coronary bypass grafts.
AB  - BACKGROUND: Superior long-term patency rates of the internal mammary artery (IMA)
      versus saphenous vein (SV) after coronary artery bypass grafting are well
      documented. Higher production rates of vasodilating and platelet-inhibiting
      mediators (prostacyclin and nitric oxide) by the IMA seem to have a major impact
      on its long-term durability and resistance to coronary artery graft disease. For
      the right gastroepiploic artery (RGEA) marked release of protective mediators is
      reported as well. The vasodilating effect of cyclic guanosine monophosphate
      (cGMP) released after stimulation by atrial natriuretic peptide might serve as
      another graft protective system. The aim of the present study was to determine
      cGMP release by IMA, RGEA, and SV after atrial natriuretic peptide challenge.
      METHODS: Samples of human IMA (n = 19), RGEA (n = 7), and SV (n = 18) discarded
      during coronary artery bypass grafting were stimulated with 10(-6) mol/L atrial
      natriuretic peptide after a resting phase in nutrient medium. Release of cGMP was
      determined by 125-iodide radioimmunoassay. RESULTS: Basal cGMP production rates
      of the IMA (759.9 +/- 277.0 fmol/cm2) and RGEA (739.9 +/- 186.0 fmol/cm2) were
      higher than production rates of SV (281.2 +/- 64.0 fmol/cm2). Application of
      atrial natriuretic peptide led to a statistically significant increase of cGMP
      release in IMA grafts (1,939.3 +/- 778.0 fmol/cm2), whereas RGEA (618.4 +/- 141.3
      fmol/cm2) and SV (221.7 +/- 64.5 fmol/cm2) remained at basal levels (p < 0.05).
      CONCLUSIONS: From these data we conclude that the IMA in comparison with the RGEA
      and SV produces more extracellular cGMP when stimulated by atrial natriuretic
      peptide. This effect might support the cGMP-mediated protective properties of
      nitric oxide and could underline the extraordinary suitability of the IMA as a
      bypass conduit.

PMID- 9647070
TI  - HeartMate left ventricular assist device as bridge to heart transplantation.
AB  - BACKGROUND: Because of the limited supply of donor hearts, prospective recipients
      continue to die while on the waiting list for heart transplantation. Use of long
      term mechanical circulatory support devices as a bridge to transplantation may
      reduce this mortality. However, with the present state of technology, continued
      clinical evaluation of the various long-term, mechanical circulatory support
      devices available is mandatory. METHODS: Sixteen patients were bridged with the
      HeartMate left ventricular assist device (LVAD) to heart transplantation for New
      York Heart Association functional class IV cardiac failure. Twelve pneumatic and
      six electric devices were used. The mean cardiac index and the mean pulmonary
      vascular resistance of the patient cohort were 1.71 x min(-1) x m(-2) and 3.1
      Wood units, respectively. RESULTS: The mean LVAD support time per transplanted
      patient was 237 days, with a cumulative LVAD support time of about 7.2 years.
      Bleeding was the main operative and postoperative complication. Two patients
      suffered from neurologic complications and there were two major incidents of
      device malfunction. Twelve patients (75%) now have received a transplant, 3 (19%)
      are awaiting a transplant, and in 1 patient (6%), the device was explanted after
      spontaneous left ventricular recovery. Eleven of the 12 patients who received a
      transplant are alive and doing well. The HeartMate LVAD gave adequate circulatory
      support over extended periods of time and reversed the vital organ dysfunction.
      Since the start of the LVAD program, only 1 patient has died on our heart
      transplantation waiting list, compared to nine deaths in the 2 preceding years.
      CONCLUSIONS: The HeartMate LVAD bridge to heart transplantation can be performed
      with low post-LVAD implantation and posttransplantation mortality and offers 1-
      and 2-year posttransplantation actuarial survival rates comparable to those for
      nonbridged heart transplant recipients.

PMID- 9647071
TI  - Discrepancies between sizer and valve dimensions: implications for small aortic
      root.
AB  - BACKGROUND: Precise labeling of sizer and valve diameters is crucial for optimal
      valve selection especially in the small aortic root. This study examines the
      accuracy of manufacturers' markings on small aortic prostheses and sizers.
      METHODS: Sizer and valve dimensions of 22 different mechanical aortic prostheses
      (19 to 23 mm) were evaluated by caliper micrometer measurements. RESULTS: Nearly
      all sizers exceeded their marked dimensions by up to 1.0 mm. Measured tissue
      annulus diameters for 19-mm-labeled valves varied between 18.3 and 19.6 mm, for
      21-mm valves from 20.5 to 21.6 mm, and for 23-mm valves from 22.4 to 23.5 mm,
      respectively. The orifice areas ranged from 1.5 to 2.06 cm2 for 19-mm valves,
      from 2.0 to 2.55 cm2 for 21-mm valves, and from 2.4 to 3.09 cm2 for 23-mm valves,
      respectively. CONCLUSIONS: Actual sizer dimensions and tissue annulus diameters
      of various small mechanical aortic prostheses varied considerably from their
      marked diameters. These differences should be considered to ensure the optimal
      prosthesis selection for each patient.

PMID- 9647072
TI  - Reversibility of cardiac dysfunction after valve replacement in elderly patients
      with severe aortic stenosis.
AB  - BACKGROUND: The role of aortic valve replacement for aortic stenosis has not been
      fully defined in terms of the postoperative reversibility of cardiac dysfunction
      and pulmonary hypertension in elderly patients. METHODS: Cardiac function,
      assessed by radioisotope ventriculography and catheterization data, was evaluated
      before and after operation, and their results were compared between preoperative
      and postoperative data in each group of younger patients (<69 years, group I, n =
      29) and elderly patients (> or =70 years, group II, n = 21). RESULTS: One month
      postoperatively the peak ejection rate determined by radioisotope
      ventriculography improved significantly in comparison with the preoperative value
      in elderly patients (preoperatively, 228 +/- 38 versus postoperatively, 319 +/-
      116% end-diastolic volume per second, p < 0.05), although their preoperative peak
      ejection rate was severely depressed. The postoperative peak filling rate of the
      elderly group was not completely reversible to almost normal value, whereas that
      of the younger group was completely reversible. Early diastolic peak filling rate
      (one-third peak filling rate) was not reversible in both two groups. Pulmonary
      hypertension in the elderly patients was reversible to postoperative almost
      normal pulmonary artery pressure despite the severity of aortic stenosis
      (systolic pulmonary artery pressure preoperatively, 37 +/- 16 mm Hg versus
      postoperatively, 25 +/- 5 mm Hg, p < 0.02; diastolic pulmonary artery pressure
      preoperatively, 15 +/- 6 mm Hg versus postoperatively, 10 +/- 4 mm Hg, p < 0.05).
      CONCLUSIONS: Both cardiac dysfunction, reflected by reduction of peak ejection
      rate, and pulmonary hypertension in elderly patients with severe aortic stenosis
      were reversed, reaching almost normal values 1 month after operation.

PMID- 9647073
TI  - Significance of serum S100 release after coronary artery bypass grafting.
AB  - BACKGROUND: S100 protein has been suggested to be a serum marker for cerebral
      complications after cardiac operation and extracorporeal circulation. The aim of
      this study was to characterize the S100 release pattern after extracorporeal
      circulation in 515 consecutive patients undergoing coronary artery bypass
      grafting. METHODS: Clinical variables and outcome were prospectively registered.
      The cerebral outcome was determined by clinical examination. S100 was measured at
      the end of extracorporeal circulation, and after 5, 15, and 48 hours. RESULTS:
      After operation, 13 patients had stroke, 12 had delayed awakening, and 17 had
      encephalopathy. Early S100 release, immediately after extracorporeal circulation,
      was associated with age and perfusion time, but not with cerebral outcome.
      However, S100 release after 5 to 48 hours was associated with cerebral
      complications and risk factors for such outcome. Patients with stroke had higher
      S100 levels after 15 to 48 hours. A subset of patients with renal failure had
      overall higher S100 levels at 5 hours. CONCLUSIONS: Early and late S100 release
      indicate different mechanisms for release and emphasizes the potential power of
      this new biochemical marker for cerebral damage.

PMID- 9647074
TI  - Cerebral emboli and serum S100beta during cardiac operations.
AB  - BACKGROUND: The glial protein S100beta has been used to estimate cerebral damage
      in a number of clinical settings. The purpose of this investigation was to
      determine the correlation between cerebral microemboli and S100beta levels during
      cardiac operations. METHODS: Transcranial Doppler ultrasonography was used to
      measure emboli in the right middle cerebral artery. Emboli counts (n = 111) were
      divided into five time periods: (1) incision to aortic cannulation; (2) aortic
      cannulation to cross-clamp onset; (3) cross-clamp onset to cross-clamp release;
      (4) cross-clamp release to decannulation; and (5) decannulation to chest closure.
      The level of S100beta (n = 156) was measured at baseline, at the end of
      cardiopulmonary bypass, then 150 and 270 minutes after cross-clamp release.
      RESULTS: The level of S100beta correlated with age, cardiopulmonary bypass time,
      cross-clamp time, and number of emboli at time period 2. Although cardiopulmonary
      bypass time was univariately associated with S100beta level, it became
      nonsignificant in a multivariable model that included age and cross-clamp time.
      CONCLUSIONS: The correlation of S100beta level with emboli measured during
      cannulation (time period 2) supports the hypothesis that cannulation is a high
      risk time period for cerebral injury.

PMID- 9647075
TI  - Cardiotomy suction: a major source of brain lipid emboli during cardiopulmonary
      bypass.
AB  - BACKGROUND: Brain injury remains a significant problem in patients undergoing
      cardiac surgery assisted by cardiopulmonary bypass (CPB). Autopsy brain specimens
      of patients after cardiac operations with CPB reveal numerous acellular lipid
      deposits (10 to 70 microm) in the microvasculature. We hypothesize that these
      small capillary and arterial dilatations result from a diffuse inflammatory
      response to CPB or from emboli delivered by the bypass circuit. This study was
      undertaken to determine which aspect of CPB is most clearly associated with these
      dilatations. METHODS: Thirteen dogs were studied in four groups: group I (n = 3),
      right-heart CPB; group II (n = 2), lower-extremity CPB; group III (n = 3),
      hypothermic CPB; and group IV (n = 5), hypothermic CPB with cardiotomy suction.
      All dogs in all groups were maintained on CPB for 60 minutes and then euthanized.
      Brain specimens were harvested, fixed in ethanol, embedded in celloidin, and
      stained with the alkaline phosphate histochemical technique so that dilatations
      could be counted. RESULTS: All dogs completed the protocol. The mean density of
      dilatations per square centimeter for each group was as follows: group I, 1.77 +/
      0.77; group II, 4.17 +/- 1.65; group III, 4.54 +/- 1.69; and group IV, 46.5 +/-
      14.5. In group IV (cardiotomy suction), dilatation density was significantly
      higher than in group III (hypothermic cardiopulmonary bypass) (p = 0.04) and all
      other groups (p = 0.04). CONCLUSIONS: Blood aspirated from the surgical field and
      subsequently reinfused into dogs undergoing CPB produces a greater density of
      small capillary and arterial dilatations than CPB without cardiotomy suction,
      presumably because of lipid microembolization.

PMID- 9647076
TI  - Posterior distribution of infarcts in strokes related to cardiac operations.
AB  - BACKGROUND: Stroke complicates cardiac surgical procedures in a substantial
      number of patients. The mechanism of stroke is predominantly embolic, although
      hypoperfusion may play a role. The aim of this study was to determine whether
      radiologic appearances in this population were consistent with an embolic cause.
      METHODS: We reviewed computed tomographic scans and medical records in 24
      patients who suffered stroke after cardiac operation. Stroke was evident at 24
      hours in 19 patients (79%). Infarcts were multiple in 16 and single in 3 patients
      (group 1). The remaining 5 patients suffered stroke beyond 24 hours and had
      single infarcts on computed tomographic scan (group 2). RESULTS: In group 1, 15
      patients (79%) had bilateral cerebellar infarcts, 4 (74%) had posterior cerebral
      artery infarcts, 10 (53%) had posterior watershed infarcts, and 11 patients (58%)
      had middle cerebral artery branch infarcts. The mean number of vascular
      territories involved was 5.1 (range, 1 to 10). Mobile atheromatous plaque was
      present in the ascending aorta or arch in 5 of 9 patients (56%) in group 1. In
      group 2, stroke occurred in close association with atrial or ventricular
      fibrillation in 3 of 5 patients (60%). CONCLUSIONS: In patients with radiologic
      evidence of infarction, perioperative strokes after cardiac operation are
      typically multiple, and involve the posterior parts of the brain, consistent with
      atheroembolization. Delayed strokes may be attributable to cardiogenic embolism.

PMID- 9647077
TI  - Biomechanical study of sternal closure using rigid fixation techniques in human
      cadavers.
AB  - BACKGROUND: We believe rigid plate fixation may be superior to wire fixation in
      sternal closure, as rigid fixation used in the craniofacial skeleton has shown
      greater stability, lower postoperative pain, and accelerated bone healing. We
      hypothesize that sterna fixed with titanium plates are more stable mechanically
      than sterna fixed with wires. METHODS: The sterna from human cadavers were used
      in this two-phased study. Phase I compared wires to four-hole titanium straight
      plates. Phase II compared wires to four-hole titanium custom H plates. The sterna
      were tested biomechanically using all fixation methods. RESULTS: Phase I showed
      no statistically significant difference in the stiffness or lateral displacement
      between the wired and straight plated sterna. Phase II showed a statistically
      significant greater stiffness (p < 0.05) and less lateral displacement (p < 0.05)
      in the custom plated sterna over the wired sterna. CONCLUSIONS: Our results
      showed that custom titanium H plates were superior to wire fixation. Furthermore,
      our results established the importance of plate configuration in sternal
      fixation. Our study may have beneficial clinical implications, as decreased
      motion at the sternotomy site could mean less postoperative pain, a decreased
      incidence of infection, and accelerated bone healing.

PMID- 9647078
TI  - Radiofrequency and cryoablation of atrial fibrillation in patients undergoing
      valvular operations.
AB  - BACKGROUND: Previous studies have shown that the maze operation can restore sinus
      rhythm and atrial transport function in patients with chronic atrial
      fibrillation. The purpose of this study was to test the feasibility of the
      application of radiofrequency and cryoablation as an alternative to the classic
      maze operation. METHODS: Twelve patients undergoing mitral valve procedures were
      included in this study. Radiofrequency and cryoablation were applied to create
      lesions in both atria to simulate the classic maze operation. RESULTS: There were
      two surgical deaths. At the mean follow-up of 10.25 months for the remaining 10
      patients; 6 were in sinus rhythm, 2 in atrial rhythm, 1 in paroxysmal atrial
      tachycardia, and 1 in atrial fibrillation. Doppler echocardiography at 6-month
      follow-up showed emergence of biatrial transport function in 3 patients and right
      atrial contractility in 8. At 12-month follow-up of 5 patients, Doppler
      echocardiography showed biatrial transport function in 3 and right atrial
      contractility in 4. CONCLUSIONS: Our modified maze procedure during valvular
      operation is effective for achieving an acceptable success rate to restore sinus
      rhythm and atrial transport function in patients with chronic atrial
      fibrillation.

PMID- 9647079
TI  - Bilateral thoracoscopic minimally invasive direct coronary artery bypass grafting
      using internal thoracic arteries.
AB  - BACKGROUND: Single-vessel coronary artery bypass grafting of the left internal
      mammary artery (ITA) to the left anterior descending coronary artery using a
      minithoracotomy has been shown to produce excellent results with a very low
      mortality. However, this procedure cannot be used in patients with double- or
      triple-vessel disease. Our goal was to develop a minimally invasive direct
      coronary artery bypass grafting procedure without cardiopulmonary bypass for
      patients with multivessel disease. METHODS: Both ITAs were thoracoscopically
      harvested using video imaging. Limited bilateral anterior thoracotomies were
      performed in the fourth intercostal spaces, thus exposing the right coronary
      artery and the left anterior descending coronary artery. The right ITA-right
      coronary artery and ITA-left anterior descending coronary artery anastomoses were
      performed without cardiopulmonary bypass using 8-0 polypropylene sutures.
      RESULTS: This procedure was successfully performed in 3 patients. The patients
      were extubated in the operating room. Postoperative angiographic studies showed
      patent left ITA and right ITA grafts. CONCLUSIONS: Bilateral thoracoscopic
      minimally invasive direct coronary artery bypass grafting can be used to treat
      patients with a proximally diseased left anterior descending coronary artery and
      right coronary artery. Bilateral thoracoscopic ITA harvesting is a less invasive
      surgical technique that may become an option for the management of multivessel
      coronary artery disease.

PMID- 9647080
TI  - Effects of cardiomyoplasty on right ventricular filling during volume loading.
AB  - BACKGROUND: Although cardiomyoplasty (CMP) is thought to improve ventricular
      systolic function, its effects on ventricular diastolic function are not clear.
      Especially the effects on right ventricular diastolic filling have not been fully
      investigated. Because pericardial influences are more pronounced in the right
      ventricle than in the left ventricle, CMP with its external constraint may
      substantially impair right ventricular diastolic filling. METHODS: Fourteen
      purebred adult beagles were used in this study. Seven underwent left posterior
      CMP, and 7 underwent a sham operation with a pericardiotomy and served as
      controls. Four weeks later, the hemodynamic effects of CMP were evaluated by
      heart catheterization before and after volume loading (central venous infusion of
      10 mg/kg of 4.5% albumin solution for 5 minutes). RESULTS: In the CMP group, mean
      right atrial pressure and right ventricular end-diastolic pressure increased
      significantly from 3.1 +/- 1.2 mm Hg to 6.1 +/- 2.0 mm Hg (p < 0.001) and from
      4.0 +/- 1.8 mm Hg to 9.6 +/- 2.5 mm Hg (p < 0.001), respectively. Volume loading
      in the control group did not significantly increase either variable. Right
      ventricular end-diastolic volume and stroke volume did not change significantly
      (from 53 +/- 9.3 mL to 60 +/- 9.0 mL and from 20 +/- 2.3 mL to 21 +/- 3.2 mL,
      respectively) in the CMP group. In the control group, however, right ventricular
      end-diastolic volume and stroke volume increased significantly from 45 +/- 7.7 mL
      to 63 +/- 14 mL (p < 0.05) and from 18 +/- 4.3 mL to 22 +/- 4.2 mL (p < 0.05),
      respectively. CONCLUSIONS: These results suggest that CMP may reduce right
      ventricular compliance and restrict right ventricular diastolic filling in
      response to rapid volume loading because of its external constraint.

PMID- 9647081
TI  - Postischemic function and protein kinase C signal transduction.
AB  - BACKGROUND: The protective effects of myocardial preconditioning may occur by way
      of multiple mechanisms, with G-protein-mediated protein kinase C (PKC)
      translocation as a final common pathway. In this study we investigate the
      pharmacologic induction of preconditioning, by PKC translocation, using PKC
      agonists/antagonists to reveal its effects on contractile function after
      myocardial ischemia. METHODS: Langendorff-perfused rabbit hearts received: (1)
      control; (2) dimethyl sulfoxide (vehicle); (3) acetylcholine (0.55 mmol/L; PKC
      agonist); (4) 1,2-s,n-dioctanoylglycerol (DOG; 22 mmol/L; PKC agonist); (5)
      chelerythrine (0.8 mmol/L; PKC antagonist); or (6) DOG-chelerythrine followed by
      a 2-hour ischemic period, using modified St. Thomas cardioplegia and a 45-minute
      reperfusion period. The period of ischemia was chosen so as to allow for
      improvement by appropriate agonists. To observe metabolic changes, tissue
      nucleotides and nucleosides were measured. Membrane and cytosolic fractions of
      PKC were determined by an anti-PKC antibody directed against the PKC delta
      isozyme. Lactate levels and myocardial pH were measured. RESULTS: The PKC
      agonists DOG and acetylcholine showed the greatest recovery of developed pressure
      (68% +/- 2%, 60% +/- 9%, respectively). Although pH, lactate, and nucleotide
      levels were similar between groups at all times, myocyte PKC translocation
      demonstrated 25% of PKC delta isoforms on cell membrane sites during baseline,
      which shifted to 67% delta 17% with unprotected ischemia. DOG mimicked this shift
      with 58% delta 12% of PKC delta isoforms on membranes, which was also blocked by
      chelerythrine to 35% +/- 7%. CONCLUSIONS: These data demonstrate that PKC
      translocation results in improved postischemic function, not by alteration of
      energetics or metabolism, and deserves further investigation.

PMID- 9647082
TI  - Expression of vascular adhesion molecules in saphenous vein coronary bypass
      grafts.
AB  - BACKGROUND: Adhesion of blood elements to the endothelium is an important step in
      the development of vein graft disease. This study examines the expression of
      vascular adhesion molecules on explanted saphenous vein bypass grafts. METHODS:
      Immunocytochemical staining was performed using explanted saphenous vein grafts
      from 28 patients. Antibodies against the endothelial markers CD31, von Willebrand
      factor, intercellular adhesion molecule-1, vascular adhesion molecule-1, and E
      selectin were used. RESULTS: Staining for CD31 and von Willebrand factor
      demonstrated the presence of endothelial cells in the lumen and the vasa vasorum.
      Expression of intercellular adhesion molecule-1 was variable between grafts,
      whereas vascular adhesion molecule-1 and E-selectin were almost always absent on
      the luminal endothelium. In contrast, the endothelium of the vasa vasorum stained
      positively for intercellular adhesion molecule-1 and vascular adhesion molecule
      1, and was also seen on nonendothelial cells within the vessel wall. Expression
      of these adhesion molecules did not vary with the severity of vein graft disease.
      CONCLUSIONS: This study highlights the blood vessels in the adventitia as
      possible sites for the adhesion and migration of cells into the vessel wall.

PMID- 9647083
TI  - The role of platelet-activating factor in regional myocardial ischemia
      reperfusion injury.
AB  - BACKGROUND: This swine model was designed to elucidate the role of platelet
      activating factor in regional myocardial ischemia-reperfusion injury. METHODS: In
      groups 1 and 2 (n = 12 each), the left anterior descending coronary artery was
      ligated for 60 minutes to induce regional myocardial ischemia followed by 6 hours
      of reperfusion. Group 1 received the platelet-activating factor antagonist TCV
      309 before ischemia, whereas group 2 did not. Group 3 (n = 3) had a sham
      operation. RESULTS: Animals in group 2 exhibited significant (p < 0.05)
      hemodynamic instability and myocardial depression during the reperfusion period.
      Despite preventive measures, 7 of the 12 animals experienced severe dysrhythmias
      in the form of atrial and ventricular fibrillation leading to cardiac arrest. In
      contrast, animals in group 1 in whom the effects of platelet-activating factor
      were blocked by the specific platelet-activating factor receptor antagonist TCV
      309 were hemodynamically stable and had significantly (p < 0.05) better
      myocardial function. This significant difference in global myocardial function
      between the groups was observed in the presence of similar morphologic findings
      and regional myocardial function. CONCLUSIONS: These results suggest that
      platelet-activating factor has a definite influence on global myocardial
      dysfunction associated with regional myocardial ischemia-reperfusion injury.

PMID- 9647084
TI  - Total simultaneous repair of coarctation and intracardiac pathology in adult
      patients.
AB  - BACKGROUND: Thoracic aortic coarctation accompanied by a second surgically
      reparable lesion is a rare combination in the adult patient. The simultaneous
      operative management of both lesions is desirable because of the higher morbidity
      and mortality that would occur with staged procedures. METHODS: We describe the
      simultaneous operative management in three adult patients with coarctation and a
      second cardiac lesion. All 3 patients had intrapericardial ascending aorta
      descending aorta bypass and concomitant repair of a cardiac lesion. The attendant
      repairs in the 3 patients, respectively, were aortic valve replacement,
      orthotopic heart transplantation, and coronary artery bypass grafting. RESULTS:
      Double arterial cannulation, retrograde cardioplegia, large-bore aorto-aortic
      bypass grafts, and early use of alpha-agonists to stabilize systemic pressure
      were all key to ensuring safe conduct of the operation. Each patient had an
      essentially uneventful postoperative course. CONCLUSIONS: Thoracic coarctation
      and concomitant cardiac pathology can be safely and readily managed with a single
      stage approach involving cardiac repair and extraanatomic ascending aorta
      descending aorta bypass grafting. A review of the English-language literature of
      patients managed similarly is included.

PMID- 9647085
TI  - Cerebral and systemic embolization during left ventricular support with the
      Novacor N100 device.
AB  - BACKGROUND: Patients undergoing implantation of left ventricular assist systems
      (LVAS) are prone to thromboembolic complications. We analyzed the incidence,
      clinical findings, and outcome of neurologic and systemic thromboembolic events
      (TE) in patients with the Novacor N100 LVAS. In a subset of patients,
      transcranial Doppler sonography was used to detect microembolic signals. METHODS:
      Thirty-six patients underwent implantation of a Novacor N100 LVAS for various
      reasons. The surgical procedure was elective in 18 patients and scheduled on an
      urgent or emergency basis in another 18 patients. The assist period lasted from
      17 to 336 days (109 +/- 88 days); 22 patients were forwarded to heart
      transplantation after being supported for 140 +/- 87 days. RESULTS: Clinical
      cerebral embolism was evident in 17 patients (47%). Thromboembolic events were
      singular in 8 and multiple in 9 patients; in the latter up to 10 TE occurred
      (mean +/- SD, 1.4 +/- 2 TE). Leading neurologic symptoms were unilateral
      hemiplegia in 11, as well as ocular symptoms and aphasia in 12 patients each.
      Noncerebral TE were detected in 4 patients, 2 of whom underwent an emergency
      operation for intestinal and iliac artery occlusion. The incidence of TE did not
      correlate strongly with the interval of LVAS support. Cerebral computed
      tomography confirmed lesions in 58% of patients. Transcranial Doppler sonography
      detected microembolic signals on 67% of all recordings, with the microembolic
      signals being more frequent on days with clinically manifest TE. The outcomes
      were good, as only 2 patients suffer from neurologic sequelae. CONCLUSIONS:
      Thromboembolism is still a major threat for patients with LVAS implantation.
      Neurologic sequelae are frequent but have a favorable prognosis, and systemic
      complications occur considerably less often. Patient selection, adequate
      anticoagulation, and transcranial Doppler sonography may help to reduce the
      incidence of TE.

PMID- 9647086
TI  - Improvement in esophageal varices and liver histology postoperatively in Budd
      Chiari syndrome.
AB  - BACKGROUND: In the past 17 years, 32 patients with Budd-Chiari syndrome were
      treated by reconstruction of the occluded inferior vena cava and reopening of the
      hepatic veins under femoro-femoral normothermic extracorporeal partial bypass.
      The mean follow-up was 8 years (range, 1.5 to 17 years). METHODS: To evaluate the
      benefits of our operative procedure, we compared the preoperative, early
      postoperative, and late postoperative endoscopic appearance of the esophageal
      varices and the histologic findings of the liver tissue obtained intraoperatively
      and at a later date. RESULTS: The esophageal varices found preoperatively in 29
      patients (90.6%) had disappeared in 7 patients by the time of discharge, and in 2
      patients they disappeared 4 to 7 years after surgery. In the remaining 20
      patients, the grade of the esophageal varices was reduced markedly. Histologic
      examination of the liver showed cirrhosis in 22 patients, fibrosis in 9 patients,
      and severe congestion in 1 patient. Inspection of the liver in the late
      postoperative period (in 10 patients) showed improvement in centrilobular
      congestion and no increase in interlobular fibrosis. CONCLUSIONS: Gradual and
      steady improvement of esophageal varices and hepatic fibrosis can be achieved
      after our operative procedure.

PMID- 9647087
TI  - Complement activation and cytokine generation after modified Fontan procedure.
AB  - BACKGROUND: The modified Fontan procedure separates the systemic and pulmonary
      circulations in patients born with a functional single ventricle. Delayed
      recovery is frequently observed after this procedure. It was our hypothesis that
      complement activation or cytokine generation may contribute to the
      pathophysiology of this problem. METHODS: We measured activated complement C3,
      thromboxane B2, interleukin-6, and tumor necrosis factor-alpha levels by
      immunoassay in 16 patients undergoing Fontan procedure. Patient plasma samples
      were obtained preoperatively, on initiation of cardiopulmonary bypass, after
      administration of protamine, and 1, 4, 8, and 24 hours postoperatively. RESULTS:
      There was no early or late mortality in this cohort of patients. Low cardiac
      output developed in 3 of 16 patients, and pleural effusions developed in 5. The
      median length of hospital stay was 9 days. Activated complement C3 levels
      increased from a baseline of 1,486 +/- 564 to 4,600 +/- 454 ng/mL after
      cardiopulmonary bypass and administration of protamine, and returned to baseline
      by 24 hours. The level of interleukin-6 increased from 42 +/- 32 to 176 +/- 22
      pg/mL and at 24 hours remained elevated at 71 +/- 15 pg/mL. Neither thromboxane
      B2 nor tumor necrosis factor-alpha levels increased significantly. CONCLUSIONS:
      The data demonstrate threefold to four-fold increases in activated complement C3
      and interleukin-6, indicating that both humoral and cellular systems are
      affected. It is our conclusion that complement and cytokine activation may
      contribute to the delayed recovery observed after Fontan procedure.

PMID- 9647088
TI  - Clinical results of the staged Fontan procedure in high-risk patients.
AB  - BACKGROUND: For high-risk Fontan candidates, the introduction of a bidirectional
      Glenn shunt before total cavopulmonary connection (a two-staged strategy) may
      extend the indications for the Fontan procedure. The clinical results of the two
      staged and one-staged Fontan procedure were thus reviewed and compared. METHODS:
      Between November 1991 and July 1996, the two-staged strategy was performed in 40
      high-risk Fontan candidates with a mean interval of 17.2 months after introducing
      the bidirectional Glenn shunt (staged group). We considered a young age (<2
      years), high mean pulmonary arterial pressure (> or =20 mm Hg), high pulmonary
      vascular resistance (> or =3 Wood units), small pulmonary artery (Nakata index
      <200 mm2/m2), atrioventricular valve incompetence (> or = moderate), distortion
      of pulmonary artery, anomalous pulmonary venous return, and poor ventricular
      function as risk factors for the successful completion of Fontan circulation.
      During the same period, 68 patients underwent the modified Fontan procedure in a
      one-step fashion (primary group). RESULTS: In the staged group after the
      bidirectional Glenn shunt, the mean pulmonary arterial pressure and ventricular
      end-diastolic pressure were both found to have decreased significantly to the
      same level as those in the primary group, whereas the pulmonary artery
      demonstrated a significantly smaller size than that in the primary group.
      Operative morbidity was similar in both groups. Operative mortality was also
      similar and low in both groups (1.5% in the primary group and 0% in the staged
      group). CONCLUSIONS: A bidirectional Glenn shunt was found to be a useful interim
      palliation in high-risk Fontan candidates. This two-staged strategy may extend
      the operative indications for the Fontan procedure.

PMID- 9647089
TI  - Pulmonary root replacement with the Freestyle stentless aortic xenograft in
      growing pigs.
AB  - BACKGROUND: The stentless xenograft with its favorable hemodynamic performance on
      the left side of the heart seems an attractive, readily available alternative for
      the reconstruction of the right ventricular outflow tract in children. METHODS:
      To assess its function in a preclinical animal investigation, we replaced the
      pulmonary root with a Freestyle stentless aortic xenograft in 18 piglets of 26.6
      +/- 3.2 kg weight. The animals were allowed to grow as much as possible and
      slaughtered when symptoms of heart failure developed or body weight reached more
      than 160 kg. All valve explants were analyzed by gross examination and
      photography and, in 4 representative pigs, by histologic examination. RESULTS:
      Fourteen animals died prematurely after 2 weeks to 11 months. Twelve xenograft
      explants showed thick, immobilized, large nodular structures as cuspal remnants
      causing significant stenosis. At microscopy, large cuspal masses of degenerating
      collagen and fibrin and various inflammatory cells were frequently found. In the
      growing pig, most of the xenografts implanted in the pulmonary position showed
      early degeneration causing severe stenosis. CONCLUSIONS: Use of this valve for
      right ventricular outflow tract reconstruction in children cannot be recommended.

PMID- 9647090
TI  - Brain damage and myocardial dysfunction: protective effects of magnesium in the
      newborn pig.
AB  - BACKGROUND: Brain damage is associated with myocardial dysfunction resulting from
      excessive release of endogenous catecholamines and Ca2+ overload. Magnesium ion,
      a natural Ca2+ blocker, has recently been recognized as a myoprotective agent.
      METHODS: Myocardial function was assessed in 3- to 7-day-old piglets from
      pressure-volume data (obtained by the conductance catheter/micromanometer
      technique) before and for 4 hours after ligation of the aortic arch vessels and
      was correlated with ultrastructural changes. Group a (n = 6) received MgSO4
      immediately after induction of brain damage for 4 hours, whereas group b (n = 6)
      did not receive MgSO4 and served as control. RESULTS: In both groups after
      induction of brain damage, there was a significant (p < 0.05) increase in end
      systolic elastance and preload-recruitable stroke work that persisted for 1 hour.
      However, after 2 and 4 hours, there was a significant (p < 0.05) reduction in
      both variables in group b (end-systolic elastance, 74% +/- 5% and 59% +/- 6%,
      respectively, and preload-recruitable stroke work, 77% +/- 4% and 64% +/- 3%,
      respectively, compared with baseline), and in group a, the values returned to
      baseline. The chamber stiffness index rose significantly (p < 0.05) in group b 15
      minutes after induction of brain damage and remained significantly (p < 0.05)
      higher for 4 hours versus no significant change in group a. Plasma levels of
      epinephrine and norepinephrine were similar in the groups before and after brain
      damage. Electron microscopic study showed severe ultrastructural changes in group
      b and significantly milder changes in group a. CONCLUSIONS: We conclude that
      MgSO4 may protect the neonatal myocardium when administered immediately after
      brain damage.

PMID- 9647091
TI  - Truncal valve repair: initial experience in neonates.
AB  - BACKGROUND: The identification of moderate to severe preoperative truncal valve
      regurgitation has been synonymous with significant postoperative mortality after
      neonatal repair of truncus arteriosus. Spurned by the deficiencies of current
      truncal valve substitutes surgeons are once again reexamining the option of
      truncal valve reparative techniques. METHODS: From May 1996 until June 1997, 8
      children underwent correction of truncus arteriosus. A retrospective analysis was
      conducted. RESULTS: There was one in-hospital death secondary to a postoperative
      massive coronary air embolism. Moderate-to-severe truncal valve regurgitation was
      identified clinically and confirmed with cardiac ultrasound in 3 neonates with a
      mean age of 7 days (range, 4 to 12 days) all with quadracusp truncal valves.
      Successful truncal valve repair was accomplished in 2 infants, with a third
      neonate requiring homograft replacement with coronary reimplantation for failure
      in achieving valvular competence after attempted valvuloplasty. Postoperative
      echocardiograms in those neonates who underwent truncal valve repair confirmed a
      functional "tricuspid" valve with only mild to mild-plus regurgitation.
      CONCLUSIONS: We give further credence to the hypothesis that primary neonatal
      truncal valve repair is feasible and may be successful in the avoidance and delay
      of serial truncal valve replacements using either mechanical or allograft
      substitutes.

PMID- 9647092
TI  - Superior hydrodynamics of a modified cavopulmonary connection for the Norwood
      operation.
AB  - BACKGROUND: In the Fontan circulation, energy consumption at the cavopulmonary
      connection is crucial. Our hypothesis was that a modification of the standard
      Norwood variant of cavopulmonary connection with an extended anastomosis would
      improve hydrodynamics. METHODS: The in vitro hydrodynamics of two different
      Perspex glass models resembling the Norwood variant of cavopulmonary connection
      (model I) and the modification (model II) were analyzed in a mock circulation at
      nonpulsatile flows of 2 to 5 L/min to simulate rest and exercise. The pulmonary
      flow split was varied to imitate varying lung resistances. Inferior-to-superior
      caval flow ratio and size of models were increased to simulate growth. RESULTS:
      The pulmonary flow was preferentially directed to the left lung in model I and
      was better balanced in model II. Power losses increased exponentially with total
      flow in both models and were markedly higher in model I. These differences were
      attenuated in the larger models. Anastomotic turbulences were larger in model I.
      Power losses in both models were relatively insensitive to changes in pulmonary
      flow split. CONCLUSIONS: The proposed modification of the Norwood variant of
      cavopulmonary connection seems to be hydrodynamically advantageous and warrants
      further evaluation.

PMID- 9647093
TI  - Growth of the subclavian artery and the anastomosis in Blalock-Taussig shunt:
      absorbable versus nonabsorbable suture.
AB  - BACKGROUND: We evaluated the growth of Blalock-Taussig shunts placed with
      absorbable suture by cineangiographic findings and long-term results and compared
      them with those in an earlier group of patients in whom we used nonabsorbable
      suture. METHODS: Eighty-one patients had postoperative cineangiography 1 year or
      more after a Blalock-Taussig shunt procedure. From September 1985 to December
      1994, 40 patients (group I) underwent a Blalock-Taussig shunt procedure with the
      use of absorbable polydioxanone suture, and from January 1980 to August 1989, 41
      (group II) underwent the same operation with nonabsorbable polypropylene suture.
      Cineangiograms were reviewed to assess shunt patency and growth of the subclavian
      arteries and the subclavian artery-pulmonary artery anastomoses. RESULTS: At the
      Blalock-Taussig shunt operation, mean outer diameters of the subclavian artery
      and the anastomosis in group I were 3.8 +/- 0.1 mm and 4.1 +/- 0.1 mm,
      respectively and 3.9 +/- 0.1 mm and 4.0 +/- 0.1 mm in group II. The mean inner
      diameters of the subclavian artery and the anastomosis measured in postoperative
      cineangiograms were 7.9 +/- 0.5 mm and 4.6 +/- 0.2 mm, respectively in group I
      and 6.6 +/- 0.4 mm and 3.1 +/- 0.2 mm in group II. The diameters of both the
      subclavian artery (p < 0.05) and the anastomosis (p < 0.001) were significantly
      greater in group I than in group II. Five years after operation, 71.1% +/- 7.4%
      of patients in group I and 54.8% +/- 8.0% in group II had good palliation.
      CONCLUSIONS: The use of absorbable polydioxanone suture has an advantage in terms
      of growth of the diameters of the subclavian artery and the anastomosis in a
      Blalock-Taussig shunt and may improve the long-term results after this shunt
      operation in infancy.

PMID- 9647094
TI  - Coarctation repair: modification of end-to-end anastomosis with subclavian flap
      angioplasty.
AB  - BACKGROUND: Subclavian angioplasty and resection and end-to-end anastomosis for
      coarctation repair carry a substantial risk of recurrence of coarctation. The
      combined technique using both these methods has shown good results but requires a
      longer period of continuous cross-clamping of the aorta. METHODS: A modified
      technique using intermittent cross-clamping with a period of reperfusion between
      cross-clamping periods was used. After the end-to-end anastomosis the clamps are
      released for 10 minutes and reapplied to do the subclavian angioplasty. Between
      1991 and 1996 this was done in 26 infants (mean age, 5 weeks; range, 1 day to 6
      months; median, 3 weeks). Mean weight was 3.85 kg (range, 1.5 to 8.4 kg). Mean
      length of follow-up was 23 months. Twenty-two patients (85%) had associated
      anomalies, excluding patent ductus arteriosus, and 5 patients (19%) had another
      procedure performed at the same time. RESULTS: There was no mortality. The mean
      echocardiographic gradient was 4 mm Hg in the immediate postoperative period and
      2.9 mm Hg during follow-up. Residual or recurrent coarctation as detected by
      significant echocardiography or blood pressure gradient did not develop in any
      infant. CONCLUSIONS: This modified technique of anastomosis is an effective way
      of relieving coarctation with excellent intermediate-term results.

PMID- 9647095
TI  - Tricuspid annuloplasty and ventricular plication for Ebstein's malformation.
AB  - BACKGROUND: Seven patients with the diagnosis of Ebstein's malformation of the
      tricuspid valve were operated on. Mean age was 12 years (range, 7 to 16 years).
      All were cyanotic, with severe tricuspid regurgitation. Thromboembolism was not
      present. No associated cardiac malformations were present. METHODS: Surgical
      repair included tricuspid annuloplasty associated with longitudinal plication of
      the atrialized portion of the right ventricle. This was attained by approximating
      the anterior-posterior commissure with either the posterior-septal commissure or
      the septal leaflet remnant. The thin atrialized ventricular wall thus excluded
      remained as a cul du sac and was plicated by suturing along the longitudinal axis
      of the heart. When present, the dysplastic posterior leaflet was included in the
      plication. In essence, a monocuspid right atrioventricular valve was fashioned
      out of the anterior leaflet. The remaining septal leaflet played a minimal
      functional role. No additional procedures for treatment of arrhythmia were
      associated with the technique described. RESULTS: The postoperative course was
      uneventful in all patients. Mean follow-up is 4.3 years (range, 1 to 10 years).
      Doppler echocardiographic studies reveal satisfactory monocusp valve function in
      all patients, with adequate coaptation of the anterior leaflet and the septal
      structures. CONCLUSIONS: This technique seems applicable to most forms of
      Ebstein's malformation and is reproducible. The technique relies on the adequate
      mobilization of the anterior leaflet. Occasionally it is necessary to free
      fibrous adhesions of the leaflet to the underlying ventricular surface.

PMID- 9647096
TI  - Late results and reintervention after aortic valvotomy for critical aortic
      stenosis in neonates and infants.
AB  - BACKGROUND: Many centers have adopted balloon valvuloplasty for treatment of
      infants with critical aortic stenosis because of historically poor early results
      and a lack of long-term results with surgical valvotomy. We evaluated our results
      with open aortic valvotomy over the past decade, specifically examining factors
      influencing survival and reintervention in the current era. METHODS: From 1986 to
      1996, 37 infants in the first 3 months of life underwent open aortic valvotomy
      for critical aortic stenosis. All patients underwent cardiopulmonary bypass,
      valvotomy, and valve debridement under direct vision with standard techniques.
      RESULTS: Early mortality was 11% (4 of 37, 70% confidence limit 7% to 20%) and
      all early deaths were in neonates less than 2 weeks of age. Late death occurred
      in 6 patients a mean of 10 +/- 12 months (range, 2 to 36 months) after valvotomy.
      Actuarial survival, including operative deaths was 92% +/- 6% at 1 month, 78% +/-
      9% at 1 year, and 73.4% +/- 10% at 10 years. In a multifactorial regression
      analysis, the best predictors of death were the presence of endocardial
      fibroelastosis and small body surface area and the best predictor of the need for
      late reintervention was preoperative aortic annular size. Thirteen patients
      required reintervention: repeat operation in 7 patients, balloon valvuloplasty in
      3 patients, and both balloon valvuloplasty and reoperation in 3 patients.
      Actuarial freedom from reintervention postoperatively is 97% +/- 3% at 1 month,
      73% +/- 9% at 1 year, and 55% +/- 11% at 10 years. Reintervention was for
      recurrent left ventricular outflow obstruction in 9 patients and mixed aortic
      stenosis and aortic insufficiency in 4. Echocardiography 4.3 +/- 2.5 years after
      aortic valvotomy in survivors who have not required reintervention (n = 20)
      revealed a Doppler peak instantaneous systolic gradient of 37 +/- 14 mm Hg and
      mild or less aortic regurgitation in 16 patients and moderate aortic
      regurgitation in 4 patients. CONCLUSIONS: Current surgical results with critical
      aortic stenosis in the neonate and young infant are acceptable in terms of both
      late survival, reintervention, and functional results in the majority of
      patients. Newer interventions, such as balloon valvuloplasty, should be carefully
      evaluated for long-term results and should be compared more appropriately to
      current surgical results to determine the best treatment modality for the neonate
      and infant with critical aortic stenosis.

PMID- 9647097
TI  - Temporary aorto-pulmonary shunt for pulmonary hypertension after truncus
      arteriosus repair.
AB  - We describe successful management of pulmonary hypertension with a reversible
      aorto-pulmonary (central) shunt and inhaled nitric oxide gas after truncus
      arteriosus repair. A temporary central shunt may provide a lifeline in those
      cases refractory to pharmacologic pulmonary vasodilation as long as marginal
      systemic oxygenation can be maintained.

PMID- 9647098
TI  - Right atrial isolation for atrial fibrillation associated with atrial septal
      defect.
AB  - Two patients with atrial fibrillation associated with an atrial septal defect
      underwent simultaneous surgical correction of the atrial septal defect and right
      atrial isolation. The right atrium was surgically isolated while the continuity
      with the sinoatrial node was preserved in the remainder of the heart. After the
      operation, the patients maintained normal sinus rhythm for 99 and 65 months.
      Thus, right atrial isolation offers an alternative to the current surgical
      treatment for atrial fibrillation associated with an atrial septal defect.

PMID- 9647099
TI  - Biatrial myxoma: a rare cardiac tumor.
AB  - A previously healthy 48-year-old man presented to the hospital with a transient
      ischemic attack. Echocardiography revealed a large left atrial tumor with a
      second tumor in the right atrium. Surgical excision revealed a large left atrial
      myxoma with extension through the interatrial septum into the right atrium.

PMID- 9647100
TI  - Surgical management of tricuspid atresia and anomalous left brachiocephalic vein.
AB  - An anomalous left brachiocephalic vein is an uncommon systemic venous anomaly,
      which usually has no clinical significance. We describe a case of tricuspid
      atresia with such an anomalous left brachiocephalic vein. The presence of this
      unusual venous anomaly had a number of implications in the surgical management of
      the tricuspid atresia.

PMID- 9647101
TI  - Lung herniation secondary to minimally invasive direct coronary artery bypass
      grafting.
AB  - Lung herniation after thoracotomy is rare. We report a 66-year-old man who
      presented with this complication after undergoing attempted minimally invasive
      direct coronary artery bypass grafting. The defect was repaired with a composite
      of Marlex mesh and methyl methacrylate.

PMID- 9647102
TI  - Minimally invasive bilateral internal mammary artery bypass grafting.
AB  - We report about a 71-year-old man with coronary artery double-vessel disease who
      received minimally invasive coronary artery bypass grafting through a 9-cm left
      lateral chest incision in the third intercostal space. Both mammary arteries were
      harvested either directly (left internal mammary artery) or thoracoscopically
      (right internal mammary artery) and anastomosed to the left anterior descending
      artery and the circumflex artery through this single left lateral chest incision.
      The postoperative course was uneventful, and the patient was discharged on
      postoperative day 5.

PMID- 9647103
TI  - Large eventration of diaphragm in an elderly patient treated with emergency
      plication.
AB  - Total eventration of the hemidiaphragm is a rare condition in adults. We report a
      75-year-old woman with large eventration of the right diaphragm who required an
      emergency plication because of acute progressive respiratory distress. The
      symptom disappeared immediately after operation. Even in asymptomatic elderly
      patients with eventration, close follow-up is recommended.

PMID- 9647104
TI  - A pedunculated intraluminal foregut reduplication cyst of the proximal esophagus.
AB  - A 66-year-old woman with a 3-month history of progressive dysphagia underwent
      transoral excision of a pedunculated cyst arising in the proximal esophagus.
      Histologic examination confirmed a pedunculated intraluminal foregut
      reduplication cyst. She remains well 1 year after excision with no recurrence of
      dysphagia.

PMID- 9647105
TI  - Extubation of the patient after a difficult intubation.
AB  - A case of a difficult intubation in a heavy smoker requiring reoperative coronary
      artery bypass grafting is presented. A technique is described to extubate
      patients with marginal pulmonary function and a difficult intubation using airway
      exchange catheters.

PMID- 9647106
TI  - Repair of aortico-left ventricular tunnel originating from the left aortic sinus.
AB  - We report on a case of an 11-year-old asymptomatic child with aortico-left
      ventricular tunnel arising from the left aortic sinus. Preoperative
      transesophageal echocardiography showed a dilated aortic root with mild aortic
      valve incompetence and demonstrated the course of the tunnel, which originated
      from the left coronary sinus entering the outlet portion of the left ventricular
      outflow tract. Patch closure of the aortic end of the tunnel eliminated left
      ventricular volume overload with immediate marked reduction of cardiomegaly. At
      10-month follow-up the child is asymptomatic and receiving no oral medications.
      Control two-dimensional Doppler echocardiography shows trivial central aortic
      valve incompetence.

PMID- 9647107
TI  - Anastomosis of the left juxtaposed atrial appendages in a patient with tricuspid
      atresia.
AB  - A 9-month-old boy with left juxtaposition of the atrial appendages, tricuspid
      atresia, pulmonary atresia, and ventriculoarterial discordance underwent
      anastomosis between the atrial appendages after failure of balloon/blade atrial
      septostomy because of restrictive atrial septal defect. For surgical creation of
      atrial communication in patients with juxtaposed atrial appendages, anastomosis
      between the atrial appendages seemed to be safer, more effective, and less
      invasive than septectomy by Blalock-Hanlon technique or inflow occlusion
      technique.

PMID- 9647108
TI  - Surgical treatment of lipomatous hypertrophy of the interatrial septum.
AB  - We report a case of lipomatous hypertrophy of the interatrial septum in a patient
      with a recent syncopal episode and shortness of breath. Preoperative
      transesophageal echocardiography demonstrated a large tumor protruding from the
      interatrial septum. In addition, the patient was found to have significant
      coronary artery disease and a right internal carotid artery stenosis. The patient
      underwent successful resection of the mass with septal reconstruction,
      aortocoronary bypass, and right carotid endarterectomy. Histology of the mass was
      consistent with lipomatous hypertrophy.

PMID- 9647109
TI  - Needle embolus causing cardiac puncture and chronic constrictive pericarditis.
AB  - We present a case in which a needle broke off during intravenous injection and
      embolized to the right heart. After cardiac perforation, the needle entered the
      pericardial space and ultimately caused chronic constrictive pericarditis, which
      presented as congestive heart failure. Pericardectomy and removal of the foreign
      body via a median sternotomy were successful. Early surgical removal of
      contaminated intrapericardial foreign bodies remains a safe and effective
      approach to preventing such complications.

PMID- 9647110
TI  - Repair of mitral valve and subaortic mycotic aneurysm in a child with
      endocarditis.
AB  - Endocarditis requiring surgical intervention in children is uncommon.
      Individualized operative therapy must be fashioned to the particular pathology of
      each case. In this case we describe mitral anterior leaflet homograft patch
      augmentation valvuloplasty, subaortic homograft patch closure of a large mycotic
      aneurysm, and homograft aortic root replacement in a 3-year-old patient with
      endocarditis after remote repair of complete atrioventricular canal.

PMID- 9647111
TI  - The large window ductus: a surgical trap.
AB  - A rare window type of patent ductus arteriosus is reported that was large (15 mm
      in maximal transverse dimension) but had virtually no length and hence was
      externally invisible. The smaller aortic isthmus (4 mm in diameter), which was
      intrapericardial, was mistaken for the ductus and was inadvertently clip
      occluded, leading to death. After a specific diagnosis is made, the large window
      ductus should be patched on cardiopulmonary bypass with a transpulmonary
      approach.

PMID- 9647112
TI  - Fungal purulent constrictive pericarditis in a heart transplant patient.
AB  - Purulent pericarditis caused by Candida species is rare and is associated with
      very high mortality. Immunosuppressed transplant patients are particularly
      susceptible to fungal infections. We report a case of Candida purulent
      constrictive pericarditis in an immunocompromised heart transplant patient who
      was treated successfully with antifungal agents, surgical drainage, and
      pericardiectomy.

PMID- 9647113
TI  - A surgical method for selecting appropriate size of graft in aortic root
      remodeling.
AB  - We describe a surgical technique for selecting the appropriate size of a tube
      graft in aortic root remodeling procedures. As the technique has a geometric
      basis, we believe that our method is more accurate in determining the graft size
      than others.

PMID- 9647114
TI  - Proximal aortic control in traumatic rupture of the thoracic aorta.

PMID- 9647115
TI  - Performance of a safe proximal anastomosis in aortic dissection.
AB  - Because of the increased fragility of a freshly dissected aorta, the anastomosis
      between the aortic root and a tubular prosthesis is not forgiving of technical
      imperfections and may lead to troublesome bleeding. Providing an appropriate
      everting surface of contact and a homogeneous distribution of tension between the
      graft and aorta, as described here, should help obtain a hemostatic suture line.

PMID- 9647116
TI  - Cartilage folding method for main bronchial stapling.
AB  - Bronchopleural fistula is one of the most severe complications of lung
      operations. To prevent bronchopleural fistula, we modified the stapling technique
      to include folding of both sides of the cartilaginous main bronchus. This reduces
      the tension at the center of the membranous portion of the airway. From 1991 to
      1994, this technique was performed in 7 patients. Despite the fact that 4 of
      these patients received adjuvant therapy, none had development of a
      bronchopleural fistula.

PMID- 9647117
TI  - Use of an ultrasonic scalpel as an alternative to electrocautery in patients with
      pacemakers.
AB  - We report the safe and effective use of an ultrasonically activated scalpel as an
      alternative to unipolar electrocautery during surgical procedures in 4 patients
      with pacemakers. This scalpel provided adequate hemostasis without the adverse
      consequences of electromagnetic interference. As the scalpel was able to easily
      cut through the silicone connector sleeve of one generator, it is not recommended
      for routine generator replacement because it may damage existing pacing leads.
      However, its use during nonpacemaker operations in patients with pacemakers
      should be considered.

PMID- 9647118
TI  - The "annular sandwich": a simple method of reinforcing a friable mitral valve
      annulus.
AB  - In 6 patients undergoing prosthetic mitral valve replacement a ring of Teflon
      felt, instead of conventional Teflon pledgets, was used because of concern about
      seating a new prosthesis in a disrupted friable mitral valve annulus. The
      technique avoided the potential risk of pledget loss in the event of suture
      breakage and, in these patients, prevented postoperative paraprosthetic mitral
      valve regurgitation.

PMID- 9647119
TI  - A method for perfusion of the leg during cardiopulmonary bypass via femoral
      cannulation.
AB  - Minimally invasive approaches for cardiac operations currently are gaining
      increasing attention. Some of these approaches require cannulation of the femoral
      vessels for cardiopulmonary bypass. A potential complication of femoral
      cannulation is ischemic injury to the lower extremity in some cases that require
      long bypass times. To minimize this risk we have begun cannulating the common
      femoral artery distally, as well as proximally. This technique perfuses the leg
      for the duration of cardiopulmonary bypass, and it can be accomplished with
      minimal increases in cost and operative time.

PMID- 9647120
TI  - The birth of intracardiac surgery: a semicentennial tribute (June 10, 1948-1998)
AB  - On June 10, 1948, Charles Philamore Bailey, of Philadelphia, auspiciously
      performed the first anatomically conceived and digitally guided operation inside
      the heart: the first successful intracardiac operation. The patient, Claire Ward,
      was a 24-year-old woman afflicted with severe mitral stenosis. Dwight E. Harken
      and Russell C. Brock performed their own mitral operations very soon after
      Bailey, using new variations of methods that had been discarded about two decades
      earlier; they soon adopted the logical anatomic approach. This threesome, with
      the added contributions of Robert P. Glover--Bailey's partner at the time, in the
      role of respected and convincing teacher--opened the floodgates upon a decade of
      so-called closed heart surgery. These accomplishments, added to the earlier
      successes with the patent ductus, aortic coarctation, and "blue babies,"
      justified and strengthened the demand for precise diagnosis in cardiology--at
      that time a languishing specialty--and brought to the fore the indisputable
      requirement to operate inside the heart with maximal control. This essay calls
      attention to the semicentennial of that seminal event and reviews the origins of
      surgery for mitral stenosis.

PMID- 9647121
TI  - Positron emission tomography in lung cancer.
AB  - Reports on positron emission tomography have become more common in the oncology
      literature. After a short introduction to positron emission tomography, this
      review will look at the data relating to the use of this technology in the
      diagnosis, the staging, and the post-treatment evaluation of patients with lung
      cancer and will discuss its potential role in these evaluations.

PMID- 9647122
TI  - As originally published in 1990: Experimental study of a new porous tracheal
      prosthesis. Updated in 1998.

PMID- 9647123
TI  - The surgical meeting as infomercial.

PMID- 9647124
TI  - Mitral valve myxoma.

PMID- 9647125
TI  - Coronary artery bypass grafting: three-day discharge.

PMID- 9647126
TI  - Inflammatory aneurysm or Takayasu's disease?

PMID- 9647127
TI  - Homograft and SVC syndrome.

PMID- 9647128
TI  - Tracheobronchial laceration after double-lumen intubation for thoracic
      procedures.

PMID- 9647129
TI  - Removal of Swan-Ganz catheter via a small right anterior mediastinotomy.

PMID- 9647130
TI  - Mitral valve reconstruction.

PMID- 9647131
TI  - Total preservation of subvalvular apparatus during mitral valve replacement.

PMID- 9647132
TI  - Ultrasound detection of diaphragmatic paralysis after cardiac operations.

PMID- 9647133
TI  - Reduced complication rate in bilateral mammary artery-to-coronary artery bypass
      grafting.

PMID- 9647134
TI  - Trasylol Pediatric Investigational Meeting. Introduction.

PMID- 9647135
TI  - The Bayer 022 compassionate-use pediatric study.
AB  - BACKGROUND: As part of a compassionate-use study, a placebo-controlled study was
      undertaken to assess the efficacy of aprotinin in patients undergoing any
      procedure associated with cardiopulmonary bypass and at increased risk of
      perioperative bleeding. This article reviews results in 116 patients 16 years of
      age or less. METHODS: Patients were randomly assigned to four treatment groups:
      high dose, low dose, pump prime only, and placebo. Efficacy was measured by four
      parameters: requirement for units of donor blood, requirement for units of donor
      blood and blood product, thoracic drainage volumes, and rates of reoperation
      required primarily because of diffuse bleeding. Results were separately analyzed
      in all patients, patients undergoing primary procedures, patients undergoing
      repeat procedures, neonates and infants 1 year of age or less, and patients older
      than 1 year of age. RESULTS: There was a trend toward reduced blood and blood
      product requirements with aprotinin use, least evident in neonates and infants
      and particularly evident in patients undergoing repeat procedures. Aprotinin did
      not reduce drainage volumes in this pediatric population. CONCLUSIONS: There is a
      trend toward benefit with aprotinin use in a pediatric population, as measured by
      requirement for blood and blood product, in patients who are more than 1 year of
      age and in patients undergoing a repeat operation rather than a primary
      sternotomy operation.

PMID- 9647136
TI  - Effects of cardiopulmonary bypass and use of modified ultrafiltration.
AB  - BACKGROUND: Hemodilution is a prominent problem in cardiopulmonary bypass in a
      pediatric population. Ultrafiltration is a method used to reduce fluid volume and
      tissue edema and to increase hematocrit without the need for blood products.
      Modified ultrafiltration may offer advantages in comparison with conventional
      ultrafiltration. METHODS: This article reviews the technique of modified
      ultrafiltration and its use, results, complications, and safety in pediatric
      cardiopulmonary bypass. RESULTS: Modified ultrafiltration in pediatric
      cardiopulmonary bypass reduces total body water and serum levels of inflammatory
      mediators. It results in an elevated hematocrit without the need for transfusion,
      improved pulmonary compliance in the immediate postbypass period, and probably
      improved cerebral metabolic recovery after deep hypothermic circulatory arrest.
      CONCLUSIONS: Modified ultrafiltration can be performed safely in neonatal
      patients after cardiopulmonary bypass and offers advantages in comparison with
      conventional ultrafiltration.

PMID- 9647137
TI  - Review of efficacy parameters.
AB  - BACKGROUND: The deleterious effects of cardiopulmonary bypass are greater in
      pediatric patients than in adults. The use of aprotinin to manipulate hemostasis
      has become an important factor in attempts to reduce adverse consequences of
      these effects. METHODS: This article reviews the literature on the use of
      aprotinin in pediatric cardiac surgery. RESULTS: Available studies have many
      deficiencies, often including lack of placebo control, nonhomogeneous populations
      and procedures, and absence of information on aprotinin plasma concentrations.
      Comparison of trial results is further complicated by differences in dose
      regimens, heparin-protamine protocols, and priming. CONCLUSIONS: Further trials
      are required to adequately assess aprotinin effect on platelet preservation,
      particularly in neonates, to evaluate aprotinin's antiinflammatory action, and to
      determine optimum dosages to achieve specific objectives. Aprotinin in pediatric
      cardiac surgery has been found to be associated with no adverse effects, to
      decrease fibrinolytic and probably platelet activation, and to offer important
      clinical benefits in specific groups of patients.

PMID- 9647138
TI  - Activation of hemostasis during cardiopulmonary bypass and pediatric aprotinin
      dosage.
AB  - BACKGROUND: Cardiopulmonary bypass results in inappropriate activation of the
      coagulation and fibrinolytic systems. Factors such as a greater degree of
      hemodilution, use of deep hypothermic circulatory arrest, the impact of cyanosis
      on coagulation, and the immature coagulation system of the newborn will increase
      the risk of problematic perioperative bleeding. METHODS: This article describes
      the characteristics of the hemostatic system in children undergoing cardiac
      operations and addresses the effect of aprotinin on hemostasis. Hemostatic
      parameters were measured in 96 pediatric patients using three different doses of
      aprotinin. The high-dose group (group 1) received 30,000 KIU/kg (4.2 mg/kg) of
      aprotinin after induction of anesthesia and an additional bolus of 30,000 KIU/kg
      (4.2 mg/kg) into the pump prime. In the low-dose group (group 2), both the
      initial bolus and the pump-prime dose of aprotinin were halved to 15,000 KIU/kg
      (2.1 mg/kg). Group 3 received the high dose with an additional bolus of aprotinin
      to the pump prime. RESULTS: Plasma levels of aprotinin in both groups 1 and 2
      were lower than the 200 KIU/mL (0.03 mg/mL) value usually reached in adults with
      high-dose aprotinin treatment. Group 3 patients had levels greater than 200
      KIU/mL (0.03 mg/mL) throughout the procedure. Biochemical indices of fibrinolysis
      (fibrin[ogen] degradation products, D-dimers) revealed significant and dose
      dependent inhibition at all three aprotinin concentrations. In contrast,
      significant changes in coagulation activation markers (prothrombin fragments
      F1.2, thrombin-antithrombin III complex, and fibrin monomers) were found only in
      group 3. CONCLUSIONS: The inverse relationship between a small patient's blood
      volume and the large pump-prime volume requires additional aprotinin to be added
      to the prime to achieve plasma levels sufficient to inhibit activation of the
      coagulation cascade.

PMID- 9647139
TI  - Pharmacoeconomics analysis in a pediatric population.
AB  - BACKGROUND: Pharmacoeconomics is becoming increasingly important in the health
      care environment, but pharmacoeconomic studies are fraught with problems.
      Pharmacoeconomics can be applied to analysis of the benefits of pharmacologic
      hemostasis. METHODS: This article reviews the available methods of
      pharmacoeconomic analysis and their inherent methodologic concerns. It reviews
      pharmacoeconomic studies of pharmacologic hemostasis, with particular focus on
      the Pediatric Reoperative Open Heart Surgery study. In this study, patients were
      randomized to receive either high-dose aprotinin, low-dose aprotinin, or placebo.
      Results were analyzed from the viewpoint of cost-benefit, cost-effectiveness
      calculated with use of a roll-back decision tree, and cost-effective ratios.
      RESULTS: Cost-benefit analysis showed low-dose aprotinin to have a greater cost
      benefit than high-dose aprotinin, cost-effectiveness analysis and analysis of
      cost-effective ratios showed high-dose aprotinin to be more cost-effective than
      low-dose aprotinin, and all analyses showed aprotinin to be preferable to
      placebo. CONCLUSIONS: Aprotinin in pediatric repeat open heart operations not
      only has a cost-benefit but is cost-effective as well.

PMID- 9647140
TI  - Endothelial-related coagulation in pediatric surgery.
AB  - BACKGROUND: The endothelium plays a pivotal role in the regulation of
      anticoagulant and procoagulant pathways and imbalance can produce disturbances in
      coagulation. Serine protease inhibitors are also important controllers of the
      coagulation system. Aprotinin can reduce postoperative bleeding, although the
      mechanism of action is not clearly defined. This article focuses on a study in
      children with congenital heart disease scheduled for cardiac operations to
      determine the influence of aprotinin on plasmatic or endothelial-related natural
      inhibitors. METHODS: Thirty children were randomly allocated either to an
      aprotinin-treated group or to a control group. Levels of thrombomodulin, protein
      C, free protein S, and thrombin/antithrombin complex were measured before,
      during, and after cardiopulmonary bypass until the first postoperative day.
      RESULTS: Levels of antithrombin III, protein C and protein S, and fibrinogen,
      platelet count, and activated partial thromboplastin time were without
      differences between the two groups. Thrombin/antithrombin plasma concentrations
      increased significantly during cardiopulmonary bypass, without showing any
      differences between aprotinin-treated and nontreated children. Thrombomodulin
      plasma concentrations during cardiopulmonary bypass and until 5 hours after
      cardiopulmonary bypass were significantly lower in the aprotinin-treated children
      than in the control group. By the first postoperative day, the levels in the
      aprotinin-treated patients had returned to baseline. CONCLUSIONS: The results
      suggest a direct or indirect effect of aprotinin on endothelial cell
      thrombomodulin expression and release in a soluble form into the circulation.
      Whether the lower plasma concentrations with aprotinin are related to suppression
      of proinflammatory mediators and preservation of endothelial cell function or
      whether aprotinin has a direct action on thrombomodulin expression by the
      endothelium can only be speculated.

PMID- 9647141
TI  - Incidence of hypersensitivity reactions.
AB  - BACKGROUND: Aprotinin is a naturally occurring serine protease inhibitor derived
      from bovine lung. In common with all foreign proteins, it possesses antigenic
      properties and has the possibility of allergic reactions on reexposure. METHODS:
      Data are presented on the incidence of adverse reactions to aprotinin and the
      time course of antibody development after initial exposure. Recommendations for
      reducing the risk and sequelae of these adverse reactions are emphasized and case
      reports are reviewed. RESULTS: The incidence rates of aprotinin-related reactions
      to date (May 1997) at the German Heart Center are 2.7% in the adult population in
      reexposures (5/183) and 1.2% in the pediatric population (3/254), with an overall
      incidence of 1.8% (8/437). CONCLUSIONS: With the recommended precautions,
      reexposure to aprotinin in patients with a high risk of bleeding is justified,
      and the benefits of aprotinin treatment outweigh the relative risk of a serious
      allergic reaction.

PMID- 9647142
TI  - Neurologic sequelae associated with deep hypothermic circulatory arrest.
AB  - BACKGROUND: Earlier studies of the incidence of neurologic disturbances after
      deep hypothermic circulatory arrest produced conflicting results. This article
      reviews the results of the Boston Circulatory Arrest Study, and another study
      undertaken to compare neurologic outcome in infants after deep hypothermic
      circulatory arrest using alpha-stat and pH-stat strategies. METHODS: The study
      population in the Boston Circulatory Arrest Study consisted of 171 infants less
      than 3 months of age. Neurologic outcomes were evaluated perioperatively, at 1
      year, and at 4 years. The study population in the alpha-stat versus pH-stat study
      consisted of 182 infants no older than 9 months of age. Patients were evaluated
      for postoperative electroencephalographic (EEG) and clinical seizures, recovery
      time to first EEG activity, and postoperative mortality and morbidity. RESULTS:
      After about 30 minutes of circulatory arrest there was increasing probability of
      perioperative clinical seizures, EEG seizures, and increased time to recovery of
      EEG activity. One-year evaluations showed a significant relation of duration of
      circulatory arrest to lowered psychomotor developmental index and increased
      neurologic abnormalities. Four-year evaluations showed no difference between low
      flow and circulatory-arrest patients in results of neurologic examination or in
      full-scale general IQ, although there was an effect of circulatory arrest
      duration on various subscores of cognitive function. Compared with the pH-stat
      strategy, the alpha-stat strategy tended to be associated with more EEG seizures
      and higher postoperative morbidity and mortality, and was significantly
      associated with longer recovery time to first EEG activity. CONCLUSIONS: These
      studies strongly suggest that in infants undergoing open heart operations for
      complex congenital heart defects, low-flow bypass is associated with better
      neurologic outcome than is circulatory arrest and that the pH-stat strategy is
      associated with a better outcome than the alpha-stat strategy when circulatory
      arrest is used.

PMID- 9647143
TI  - Use of aprotinin in pediatric organ transplantation.
AB  - BACKGROUND: Pediatric thoracic organ transplantation is associated with an
      increased risk of perioperative bleeding. Many of these patients are undergoing
      repeat surgical procedures and in general require cardiopulmonary bypass.
      METHODS: This article reviews the efficacy and safety of the serine protease
      inhibitor aprotinin in improving hemostasis in pediatric transplantation.
      RESULTS: A review of the literature and investigations from Children's Hospital
      of Philadelphia suggest that aprotinin is beneficial in pediatric lung
      transplantation: high-risk patients do as well as low-risk patients. Aprotinin
      also appears to be of benefit in redo heart transplantations, particularly in
      patients who have had previous sternotomy or previous transplantation. Repeat use
      of aprotinin appears to be safe and does reduce blood loss in retransplantation
      patients. Use in the pump prime and a maintenance dose of aprotinin may be the
      most effective protocol. At this time, however, it is uncertain whether aprotinin
      is valuable in primary heart transplantation in low-risk patients. CONCLUSIONS:
      Current practice at Children's Hospital of Philadelphia is to use aprotinin in
      all lung and heart-lung transplantations and in all redo transplantations: lung,
      heart-lung, and heart. The use of aprotinin in primary heart transplantations is
      limited to patients who have had previous sternotomies or thoracotomies.

PMID- 9647144
TI  - Is medical management of menorrhagia obsolete?

PMID- 9647145
TI  - Prenatal screening.

PMID- 9647146
TI  - Non-invasive fetal cell isolation from maternal blood.

PMID- 9647147
TI  - Ovarian neoplasia and subfertility treatments.

PMID- 9647148
TI  - Randomised comparative trial of the levonorgestrel intrauterine system and
      norethisterone for treatment of idiopathic menorrhagia.
AB  - OBJECTIVE: To compare the efficacy and acceptability of the levonorgestrel
      intrauterine system and norethisterone for the treatment of idiopathic
      menorrhagia. DESIGN: A randomised comparative parallel group study. SETTING:
      Gynaecology outpatient clinic in a teaching hospital. PARTICIPANTS: Forty-four
      women with heavy regular periods and a measured menstrual blood loss exceeding 80
      ml. METHODS: Twenty-two women had a levonorgestrel intrauterine system inserted
      within the first seven days of menses, and 22 women received norethisterone (5 mg
      three times daily) from day 5 to day 26 of the cycle for three cycles. MAIN
      OUTCOME MEASURES: The main outcome measure was the change in objectively assessed
      menstrual blood loss after three months of treatment. RESULTS: When menstrual
      blood loss at three months was expressed as a percentage of the control, the
      levonorgestrel intrauterine system reduced menstrual blood loss by 94% (median
      reduction 103 ml; range 70 to 733 ml), and oral norethisterone by 87% (median
      reduction 95 ml; range 56 to 212 ml). After three cycles of treatment 76% of the
      women in the levonorgestrel intrauterine system group wished to continue with the
      treatment, compared with only 22% of the norethisterone group. CONCLUSIONS: Both
      the levonorgestrel intrauterine system and oral norethisterone in this regimen
      provided an effective treatment for menorrhagia in terms of reducing menstrual
      blood loss to within normal limits. The levonorgestrel intrauterine system was
      associated with higher rates of satisfaction and continuation with treatment, and
      thus offers an effective alternative to currently available medical and surgical
      treatments for menorrhagia.

PMID- 9647149
TI  - A randomised comparison of strategies for reducing infective complications of
      induced abortion.
AB  - OBJECTIVES: To determine lower genital tract carriage rates of C. trachomatis, N.
      gonorrhoeae and bacterial vaginosis among women seeking termination of pregnancy.
      To compare two clinical management strategies for minimising the risks of
      infective morbidity after induced abortion. DESIGN: Prevalence of infections was
      assessed by screening women undergoing abortion. Clinical management strategies
      were compared by a randomised trial. SETTING: The gynaecology departments of four
      hospitals in Scotland. PARTICIPANTS: 1672 women undergoing induced abortion.
      INTERVENTIONS: Women randomised to prophylaxis received metronidazole 1 g
      rectally before abortion plus doxycycline 100 mg twice daily for seven days.
      Women randomised to screen-and-treat received appropriate antibiotics only if
      screening proved positive for one or more infection. MAIN OUTCOME MEASURES:
      Prevalences of infections; morbidity in the eight weeks following abortion as
      assessed by reported symptoms, general practitioner consultation and prescription
      rates and hospital re-attendances; costs to the NHS of alternative managements.
      RESULTS: Prevalence rates: C. trachomatis 5.6%; N gonorrhoeae 0.19%; bacterial
      vaginosis 17.5%. Overall, women allocated to receive prophylaxis had lower rates
      of measures of short term infective morbidity than those allocated to screen-and
      treat. These differences only reached statistical significance for women who were
      reported negative on screening. The direct costs to the NHS of prophylaxis and
      screen-and-treat were calculated to be 8.17 and 18.34 per woman, respectively.
      CONCLUSIONS: Prevalences of lower genital tract infections which have been
      implicated in increased rates of infective morbidity after abortion are similar
      to those reported elsewhere. Universal antibiotic prophylaxis is at least as
      effective as a policy of screen-and-treat in minimising the risk of short term
      infective morbidity and is far more cost efficient.

PMID- 9647150
TI  - Impact of surgery for stress incontinence on the social lives of women.
AB  - OBJECTIVE: To assess the feasibility of collecting disease-specific and generic
      data on the impact of surgery on the social lives of women with stress
      incontinence; to describe the social impact of surgery in a representative group;
      and to determine the effect of timing on the assessment of outcome. DESIGN:
      Longitudinal study; questionnaires before and three, six, and twelve months after
      surgery. SETTING: Eighteen hospitals in North Thames region. PARTICIPANTS: Four
      hundred and forty-two women undergoing surgery for stress incontinence between
      January 1993 and June 1994. MAIN OUTCOME MEASURES: Post-operative recovery time,
      stress incontinence symptom impact index, activities of daily living, and cost of
      protection. RESULTS: Post-operative recovery was uneventful for most women, but
      three months after surgery 24% of those in paid employment beforehand were still
      on sick or unpaid leave. Most women (75%) reported that stress incontinence had
      less adverse impact on their lives three months after surgery, though 18%
      reported no change, and 7% felt life was worse. The likelihood of improvement was
      similar regardless of whether pre-operative urodynamic studies had been
      conducted. The extent of improvement was dependent on pre-operative severity.
      Similar findings were obtained six and twelve months after surgery. After an
      initial slight but nonsignificant deterioration in their ability to carry out
      activities of daily living, women gained a slight benefit from surgery
      (proportion with no or only slight limitation rose from 72% to 82%; P=0.0001).
      The mean cost of protection (pads and towels) fell from 8.59 pound sterling a
      month before surgery to 2.99 pound sterling a month one year after surgery, by
      which time 68% of women were not using protection. In contrast, 11% were still
      spending over 10 pound sterling a month. CONCLUSIONS: It is possible to collect
      standard data on the impact of surgery on social functioning and, thus, provide
      women with better information on likely outcomes. The benefits of pre-operative
      urodynamic investigations need to be assessed. The stability of the outcome
      measures over the first post-operative year suggest that outcomes need to be
      assessed only once and at any time from three to twelve months after the
      operation.

PMID- 9647151
TI  - A multicentre study comparing cervicography and cytology in the detection of
      cervical intraepithelial neoplasia.
AB  - OBJECTIVE: To evaluate in a multicentre setting the performance of cervicography
      compared with cytology for the detection of cervical intraepithelial neoplasia.
      DESIGN: Prospective comparative multicentre study. SETTING: Three hospitals with
      outpatient gynaecology clinics and three cancer screening clinics. PARTICIPANTS
      AND METHODS: Cervical cytology and cervicography were performed on 5724 women. If
      one or both tests showed an abnormality suggestive of at least a low grade
      squamous intraepithelial lesion, a colposcopy with directed biopsy was carried
      out. Cervicograms were evaluated by four experienced 'senior' assessors and by
      ten new 'junior' assessors. RESULTS: Results were fully analysed for 5192 women
      (91%). A cervical biopsy was carried out on 228 women and this confirmed a true
      positive lesion in 116 cases (incidence rate: 2.2%). Of these, 72 cases (62.1%)
      were detected by cervicography and 64 (55.2%) by cytology. This difference was
      not statistically significant (McNemar: P=0.475). Only 20 cases of CIN (17%) were
      concordantly detected by both tests. Senior assessors performed significantly
      better with a detection capacity of 80.6% compared to a detection capacity of
      56.6% for the junior assessors (chi2 test: P=0.034). CONCLUSIONS: Cervicography
      must be considered as a complementary test to cytology. Overall detection of CIN
      is improved, but this is mainly due to the detection of more low grade lesions.
      The lower sensitivity and specificity in high grade lesions compared with
      cervical cytology is the main limitation of cervicography in screening for CIN.
      An important finding was that the performance of cervicography was highly
      dependent on the assessors' experience.

PMID- 9647152
TI  - The rise in caesarean section rate: the same indications but a lower threshold.
AB  - OBJECTIVE: To investigate the reasons for the rise in caesarean section rate and
      note any change in indications. DESIGN: A retrospective, descriptive study
      comparing the years 1962 and 1992. SETTING: A large city centre teaching
      hospital. RESULTS: There was an overall increase in the caesarean section rate
      from 6-8% in 1962 to 18.1% in 1992. No single cause contributed more than 30%
      towards this increase. The main indications in both years were similar: failure
      to progress (42.2% vs 36.7%) and fetal indications (18.1% vs 18.9%). The largest
      relative increases were in the malpresentation group (10.8% vs 16%) and previous
      caesarean section (4.5% vs 15.2%). CONCLUSIONS: These results suggest that there
      has been a lowering in the overall threshold concerning the decision to carry out
      a caesarean section rather than changes in obstetric management. Obstetricians
      and the women in their care have to decide whether the current balance between
      risk and benefit is acceptable or whether they wish to alter the underlying
      philosophy if any significant reduction is to be sustained.

PMID- 9647153
TI  - Effective analgesia following perineal injury during childbirth: a placebo
      controlled trial of prophylactic rectal diclofenac.
AB  - OBJECTIVE: To determine if diclofenac suppositories administered prophylactically
      produce effective and lasting analgesia following perineal injury. DESIGN: A
      randomised double blind placebo controlled trial. SETTING: York District
      Hospital. POPULATION: One hundred women sustaining objective perineal injury
      (second degree tear or episiotomy) during spontaneous vaginal delivery at term.
      METHODS: Suppositories were administered at the time of repair and approximately
      12 hours later. The suppositories were randomised prior to issue by the pharmacy
      department and contained either 100 mg diclofenac or placebo. MAIN OUTCOME
      MEASURES: Pain scores assessed at 12, 24, 48 and 72 hours after delivery using a
      six point numerical scoring system and the use of additional analgesia and local
      treatments to the perineum. RESULTS: The mean pain score was significantly
      reduced in the diclofenac group at 24, 48 and 72 hours after delivery (0.86, 0.7
      and 0.59, respectively) compared with the control group (1.64, 1.31 and 1.5; P <
      0.005). In addition there was less supplementary analgesia required (eight women
      only at 72 hours compared with 15 in the control group) and this was limited to
      paracetamol or topical treatments to the perineum. CONCLUSION: Prophylactic
      rectal diclofenac provides effective analgesia after perineal repair and its
      effect appears to be maintained into the second and third postpartum days.

PMID- 9647154
TI  - Shedding of syncytiotrophoblast microvilli into the maternal circulation in pre
      eclamptic pregnancies.
AB  - OBJECTIVE: To investigate whether syncytiotrophoblast microvilli (STBM) are shed
      into the maternal circulation in increased amounts in pre-eclamptic pregnancies
      as a possible cause of maternal vascular endothelial dysfunction. DESIGN: A time
      resolved fluoroimmunoassay was developed to measure STBM levels in peripheral and
      uterine venous plasma from normal pregnant and pre-eclamptic women. Three colour
      flow cytometry was used to assess the microparticulate nature of the STBM in
      pregnancy plasma. The effects of these plasmas on endothelial cell proliferation
      was compared and a correlation with the levels of STBM detected was sought.
      SETTING: A laboratory investigation using clinical samples obtained from an
      obstetric practice in a teaching hospital. SAMPLES: Peripheral venous plasma from
      20 women with established pre-eclampsia, 20 normal pregnant women matched for
      age, gestation and parity, and 10 nonpregnant women of reproductive age. Paired
      uterine and peripheral venous plasma taken at caesarean section from 10 women
      with pre-eclampsia and 10 unmatched normal pregnant women. RESULTS: STBM were
      detected in the plasma of pregnant women by both flow cytometry and time-resolved
      fluoroimmunoassay. Significantly higher levels of STBM were found in women with
      established pre-eclampsia (P=0.01). STBM concentrations were higher in uterine
      venous plasma than in concurrently sampled peripheral venous plasma, confirming
      their placental origin. A significant correlation was found between the amount of
      STBM in the plasma and endothelial cell inhibitory activity. CONCLUSIONS: STBM
      are shed into the maternal circulation (microvillous deportation) and are present
      in significantly increased amounts in pre-eclamptic women. They may contribute to
      the endothelial dysfunction underlying the maternal syndrome of pre-eclampsia.

PMID- 9647155
TI  - A role for noradrenaline in pre-eclampsia: towards a unifying hypothesis for the
      pathophysiology.
AB  - OBJECTIVE: To compare plasma catecholamine (noradrenaline and adrenaline) levels
      in pre-eclamptic to normotensive pregnancy, and to study the activity of
      synthetic enzymes for catecholamines in placental and trophoblastic cell
      cultures. We postulated that catecholamines might be an important signal secreted
      by the fetoplacental unit in pre-eclampsia. METHODS: We recruited 12 women with
      pre-eclampsia and 12 pregnant women with nonproteinuric hypertension undergoing
      delivery by caesarean section, 23 normotensive women undergoing elective
      caesarean section at term, and 26 normotensive primigravid women with ongoing
      pregnancies at gestations equivalent to those women with pre-eclampsia. We
      measured venous blood concentrations of catecholamines. Following delivery, we
      studied tyrosine hydroxylase (the rate limiting enzyme for catecholamine
      synthesis) activity in placental tissue of these women as well as from four
      eclamptic women not in the observer study. We used Northern blot analysis to
      quantify mRNA for tyrosine hydroxylase and dopamine-beta-hydroxylase (D-beta-H, a
      non-rate-limiting synthetic enzyme for catecholamine) in placental tissue, as
      well as in trophoblast cells in primary culture and trophoblast cell lines.
      RESULTS: Venous blood concentrations of noradrenaline were significantly higher
      in pre-eclamptic women compared with normotensive women. Tyrosine hydroxylase
      activity was greater in placental tissue from pre-eclamptic and eclamptic
      compared with normotensive pregnancies, as were mRNA levels for this enzyme. The
      mRNA levels for the non-rate-limiting D-beta-H in women with pre-eclampsia were
      similar to those in normotensive pregnancies. First trimester trophoblast cells
      in primary culture and trophoblast cell lines transcript mRNA for tyrosine
      hydroxylase and D-beta-H. CONCLUSIONS: Trophoblasts have the capacity to secrete
      catecholamines, and we found increased activity of the rate-limiting synthetic
      enzyme in placental tissue from pre-eclamptic pregnancies. We postulate that the
      higher levels of catecholamines we found in the plasma of women with pre
      eclampsia might be of placental origin. We hypothesise that in pre-eclampsia
      ischaemic trophoblast tissue secretes catecholamines as a physiological signal to
      increase maternal blood flow to the fetoplacental unit, which itself is spared
      the vasoconstrictor effects of catecholamines (placental vessels are known to be
      unresponsive to catecholamines). However, since the basic pathology--defective
      trophoblast invasion--is not corrected, the increased blood flow fails to resolve
      the ischaemia, and the secretion of catecholamines is therefore sustained or even
      enhanced. Noradrenaline is known to cause lipolysis. This results in breakdown of
      triglycerides to free fatty acids, which are oxidized to lipid peroxides. The
      latter are cytotoxic and cause widespread endothelial cell damage and
      dysfunction, culminating in the clinical syndrome of pre-eclampsia.

PMID- 9647156
TI  - Placental hormones during induced hypoglycaemia in pregnant women with insulin
      dependent diabetes mellitus: evidence of an active role for placenta in hormonal
      counter-regulation.
AB  - OBJECTIVE: To study the effect of induced hypoglycaemia on serum levels of the
      placental hormones oestriol, human placental lactogen, placental growth hormone
      and progesterone in the third trimester of pregnancy. DESIGN: A prospective
      experimental investigation. SETTING: High risk pregnancy unit and diabetes
      research unit at Karolinska Institutet Danderyd Hospital, a university hospital.
      PARTICIPANTS: Ten women with insulin-dependent diabetes mellitus in the third
      trimester of pregnancy. METHODS: Venous blood samples were collected every 15
      minutes for analyses of oestriol, progesterone, human placental lactogen and
      placental growth hormone, during the 150 min of a hyperinsulinaemic hypoglycaemic
      clamp, which maintained arterial blood-glucose level of about 2.2 mmol/l. MAIN
      OUTCOME MEASURES: Levels of analysed placental hormones during hypoglycaemia.
      RESULTS: A statistically significant increase was observed in placental growth
      hormone during hypoglycaemia (P < 0.0001), whereas the placental hormones
      progesterone, human placental lactogen and oestriol did not show changes of
      clinical significance. CONCLUSIONS: The increase in placental growth hormone
      indicates that the placenta is an endocrine organ which may take an active part
      in acute metabolic processes, such as here in the hormonal counterregulation of
      hypoglycaemia.

PMID- 9647157
TI  - Biochemical modifications of human whole saliva induced by pregnancy.
AB  - OBJECTIVE: To assess human unstimulated whole saliva components during pregnancy,
      to determine the relation, if any, between pregnancy and oral health,
      particularly total protein concentration, alpha-amylase activity, sialic acid
      content and calcium and phosphate concentrations were evaluated. DESIGN: Cross
      sectional study. PARTICIPANTS: Forty-five healthy primigravid women; 15
      nonpregnant women acted as controls. RESULTS: 1. A higher total protein content
      at 10 and 21 weeks of gestation with respect to the controls and to pregnant
      women at 40 weeks; 2. a higher alpha-amylase activity at 10 and 21 weeks of
      gestation compared with the controls and to pregnant women at 40 weeks; 3. an
      increased sialic acid content at 21 and 40 weeks; 4. decreased calcium and
      phosphorus concentrations at 21 and 40 weeks of gestation. CONCLUSIONS: Pregnancy
      modifies saliva composition. This could play a pivotal role in the incidence of
      pregnancy-induced dental caries.

PMID- 9647158
TI  - Fetal cardiac function and septal thickness in diabetic pregnancy: a controlled
      observational and reproducibility study.
AB  - OBJECTIVE: To determine the reproducibility of duplex Doppler waveform analysis
      and fetal cardiac interventricular septal thickness measurement and to compare
      these parameters in matched pregnancies with and without well-controlled maternal
      Type 1 diabetes at 18-20 weeks of gestation. DESIGN: A prospective blind twin
      cohort study and a blinded inter-observer and intra-observer agreement study.
      SETTING: A tertiary referral prenatal diagnostic unit within a university
      hospital. RESULTS: Good inter- and intra-observer agreement was found for the
      measurement of transvalvular peak flow velocities and the duration of ventricular
      ejection in the fetal heart. Inter-observer agreement for aortic flow
      acceleration rate was poor. M-mode measurement of interventricular septal
      thickness showed moderate reproducibility. The mean (SD) width of the
      interventricular septum in the fetuses of well controlled diabetic women was 2 1
      mm (0.2 mm), and was significantly greater (P=0.01) when compared with the
      corresponding value in matched controls [1.9 mm (0.2 mm)]. No cardiac functional
      differences were evident. CONCLUSIONS: On-screen video analysis of Doppler
      cardiac flow waveforms and M-mode measurement of intraventricular septal
      thickness demonstrated good reproducibility. The fetuses of well controlled
      diabetic pregnancies demonstrated signs of altered cardiac morphology early in
      pregnancy, before any evident alterations in cardiac function.

PMID- 9647159
TI  - Double-blind, placebo-controlled study of magnesium hydroxide for treatment of
      sensory urgency and detrusor instability: preliminary results.
AB  - In a prospective, randomised, double-blind, placebo-controlled study 40 women
      with sensory urgency or detrusor instability randomly received either magnesium
      hydroxide (group A) or placebo (group B). Pre- and post-treatment symptoms,
      frequency-volume charts and cystometry results were compared. Eleven of 20
      patients receiving magnesium (55%) reported a subjective improvement of their
      urinary symptoms, compared with five patients taking placebo (20%). In both study
      groups there was no statistically significant difference in pre- and post
      treatment urodynamic parameters in those reporting symptomatic improvement.
      Magnesium was well tolerated by patients in group A, and no side effects were
      reported. These results suggest that magnesium hydroxide may be beneficial for
      detrusor instability or sensory urgency in women.

PMID- 9647160
TI  - Expectant management of missed miscarriage.
AB  - The option of expectant management was offered 221 women with ultrasound
      diagnosis of missed miscarriage. Eighty-five women (38%) accepted; the remaining
      136 women chose surgical evacuation of retained products of conception. In the
      expectant management group 21 women (24.7%) had a complete miscarriage, 14
      (16.5%) had incomplete miscarriage necessitating surgery, and 50 (58.8%)
      requested surgery within 48 days from the original diagnosis. These results
      suggest that the success of expectant management of missed miscarriage is too low
      to justify its use in routine clinical practice.

PMID- 9647161
TI  - Flexible outpatient hysteroscopy without anaesthesia: a safe, successful and well
      tolerated procedure.
AB  - The objective of this study was to assess the feasibility and tolerance of
      diagnostic outpatient flexible hysteroscopy without anaesthesia. Records from 554
      consecutive patients were analysed retrospectively. Success rate, reasons for
      failure, adverse reactions and level of pain were the main outcome measures.
      Hysteroscopy was successful in 90.5% of patients and well tolerated in 93.3%;
      5.4% experienced moderate to severe pain. Inability to negotiate the cervical
      canal accounted for 47% of failed procedures and poor view for 42%. These results
      suggest that flexible outpatient hysteroscopy without anaesthesia is a successful
      and well tolerated procedure.

PMID- 9647162
TI  - Successful pregnancy in a patient with type III glycogen storage disease managed
      with cornstarch supplements.

PMID- 9647163
TI  - Ultrasound detection of vault haematoma following vaginal hysterectomy.

PMID- 9647164
TI  - Complications of laparoscopy: a prospective multicentre observational study.

PMID- 9647165
TI  - Long-term follow-up review of patients who underwent laminectomy for lumbar
      stenosis: a prospective study.
AB  - OBJECT: Decompressive laminectomy for stenosis is the most common operation
      performed in the lumbar spine in older patients. This prospective study was
      designed to evaluate long-term results in patients with symptomatic lumbar
      stenosis. METHODS: Between January 1984 and January 1995, 170 patients underwent
      surgery for lumbar stenosis (86 patients), lumbar stenosis and herniated disc (61
      patients), or lateral recess stenosis (23 patients). The male/female ratio for
      each group was 43:43, 39:22, and 14:9, respectively. The average age for all
      groups was 61.4 years. For patients with lumbar stenosis, the success rate was
      88.1 % at 6 weeks and 86.7% at 6 months. For patients with lumbar stenosis and
      herniated disc, the success rate was 80% at 6 weeks and 77.6% at 6 months, with
      no statistically significant difference between the two groups. For patients with
      lateral recess stenosis, the success rate was 58.7% at 6 weeks and 63.6% at 6
      months; however, the sample was not large enough to be statistically significant.
      One year after surgery a questionnaire was sent to all patients; 163 (95.9%)
      responded. The success rate in patients with stenosis had declined to 69.6%,
      which was significant (p = 0.012); the rate for patients with stenosis and
      herniated disc was 77.2%; and that for lateral recess stenosis was 65.2%. Another
      follow-up questionnaire was sent to patients 1 to 11 years after surgery (average
      5.1 years); 146 patients (85.9%) responded, 10 (5.9%) were deceased, and 14
      (8.2%) were lost to follow-up review. At 1 to 11 years the success rate was 70.8%
      for patients with stenosis, 66.6% for those with stenosis and herniated disc, and
      63.6% for those with lateral recess stenosis. Eleven patients who underwent
      reoperation were included in the group of patients whose surgeries proved
      unsuccessful, regardless of their ultimate outcome. There was no statistically
      significant difference in outcome between 1 year and 1 to 11 years with respect
      to stenosis, stenosis with herniated disc, and lateral recess stenosis.
      CONCLUSIONS: In conclusion, long-term improvement after laminectomy was
      maintained in two-thirds of these patients.

PMID- 9647166
TI  - Posterior atlantoaxial facet screw fixation in rheumatoid arthritis.
AB  - OBJECT: This retrospective review was conducted to determine the efficacy of
      transarticular screw fixation in a group of patients who were treated for
      rheumatoid atlantoaxial instability. METHODS: Thirty-six patients (mean age 63
      years) with rheumatoid atlantoaxial instability were treated with posterior
      atlantoaxial transarticular screw fixation supplemented with an interspinous C1-2
      strut graft-cable construct to provide immediate three-point fixation to
      facilitate bone fusion. Previous attempts at fusions by using bone grafting with
      wire fixation at other institutions had failed in six of these patients. Six
      patients underwent transoral odontoid resections for removal of large irreducible
      pannus as a first-stage procedure, which was followed within 2 to 3 days by the
      posterior procedure. Postoperatively, 33 patients were placed in hard cervical
      collars and three required halo vests because of severe osteoporosis. Of eight
      patients categorized as Ranawat Class II preoperatively, all eight returned to
      normal after surgery; of eight patients in Ranawat Class III-A preoperatively,
      four improved to Class II and four remained unchanged. All 20 patients classified
      as Ranawat Class I preoperatively recovered completely. Pain decreased or
      resolved in all patients, and there were no complications related to
      instrumentation. At follow-up review (mean 2 years), 33 patients (92%) had solid
      bone fusions, and three (8%) had stable fibrous unions. CONCLUSIONS: Posterior
      atlantoaxial transarticular screw fixation provides a good surgical alternative
      for the management of patients with rheumatoid atlantoaxial instability. This
      technique provides immediate three-point rigid fixation of the C1-2 region, thus
      obviating the need for halo vest immobilization in most cases.

PMID- 9647167
TI  - Management and results of sciatic nerve injuries: a 24-year experience.
AB  - OBJECT: The purpose of this retrospective clinical study was to present results
      and provide management guidelines for various types of sciatic injuries. METHODS:
      Over a 24-year period, 380 patients with sciatic nerve injuries were managed. In
      230 patients (60%), the injury was at the buttock level, with injection injuries
      comprising more than half of these cases. Thigh-level sciatic injury was
      evaluated in 150 cases (40%) and was usually secondary to one of four main
      causes: 1) gunshot wound; 2) femur fracture; 3) laceration; or 4) contusion.
      Patients with partial deficits uncomplicated by severe pain or with significant
      spontaneous recovery or late referral were managed medically. Surgical
      exploration was not indicated in 23% of injuries at the thigh level and almost
      50% of those at the buttock level. Most of these patients achieved partial but
      good spontaneous recovery, especially in the tibial division distribution.
      Surgical intervention was required for more complete and persistent deficits in
      either the tibial or peroneal distribution. Divisions of the sciatic nerve were
      split apart and evaluated independently. Management was guided by nerve action
      potential (NAP) recordings, which indicated whether neurolysis or resection of
      the lesion was required. Repair was then made by using sutures or more frequently
      by graft placement. In most cases in which neurolysis was performed because a
      positive NAP was recorded distal to the lesion, useful function was found in the
      peroneal distribution. Unfortunately, significant recovery occurred in only 36%
      of patients who received suture or graft repairs of the peroneal division. Good
      to-excellent outcome was common for the tibial division, even in cases in which
      repair was proximal and required lengthy grafts. The relatively favorable
      recovery of tibial as opposed to peroneal divisions of the sciatic nerve occurred
      regardless of the level or mechanism of injury. CONCLUSIONS: Surgical exploration
      and, when necessary, repair of sciatic nerve injuries is worthwhile in selected
      cases.

PMID- 9647168
TI  - Occipital plagiocephaly: a critical review of the literature.
AB  - OBJECT: The literature on occipital plagiocephaly (OP) was critically reviewed to
      determine the feasibility of establishing treatment recommendations. METHODS:
      Using standard computerized search techniques, medical literature databases
      containing peer-review articles dating from 1966 were queried for key words
      related to OP. The titles of all articles were scanned for relevance, and copies
      of potentially relevant articles published in English were reviewed. Articles in
      which treatment was discussed were categorized according to their weight of
      evidence as Class I (prospective randomized controlled trials), Class II
      (clinical studies in which data are collected prospectively or retrospective
      analyses based on clearly reliable data), and Class III (most studies based on
      retrospectively collected data) to evaluate their contribution to developing a
      consensus on the treatment of OP. Of the 4308 articles identified, all but 89
      were excluded. Based on the review of these articles, the actual incidence of OP
      is unknown, and no population-based studies of its incidence or prevalence exist.
      The reported incidence of lambdoid craniosynostosis ranges from 3 to 20% with
      differences in diagnostic criteria accounting for the variability. With the
      possible exception of a lambdoid suture that is replaced by a dense ridge of
      bone, no other diagnostic criteria have been agreed on. There were no Class I
      studies and only one Class II study provided comparisons of outcomes in more than
      one treatment group with outcomes in an untreated group. Recommended treatment
      options included observation only, mechanical interventions, and a variety of
      surgical techniques. CONCLUSIONS: Controlled clinical trials are needed before
      any form of intervention can be recommended for the treatment of OP. If surgery,
      which is expensive and potentially dangerous, is to continue to play a role in
      the management of this condition, efforts should be made to determine if patients
      with untreated OP have suffered from lack of treatment.

PMID- 9647169
TI  - Incidence of silent hemorrhage and delayed deterioration after stereotactic brain
      biopsy.
AB  - OBJECT: Many neurosurgeons routinely obtain computerized tomography (CT) scans to
      rule out hemorrhage in patients after stereotactic procedures. In the present
      prospective study, the authors investigated the rate of silent hemorrhage and
      delayed deterioration after stereotactic biopsy sampling and the role of
      postbiopsy CT scanning. METHODS: A subset of patients (the last 102 of
      approximately 800 patients) who underwent stereotactic brain biopsies at the
      Toronto Hospital prospectively underwent routine postoperative CT scanning within
      hours of the biopsy procedure. Their medical charts and CT scans were then
      reviewed. A postoperative CT scan was obtained in 102 patients (aged 17-87 years)
      who underwent stereotactic biopsy between June 1994 and September 1996. Sixty-one
      patients (59.8%) exhibited hemorrhages, mostly intracerebral (54.9%), on the
      immediate postoperative scan. Only six of these patients were clinically
      suspected to have suffered a hemorrhage based on immediate postoperative
      neurological deficit: in the remaining 55 (53.9%) of 102 patients, the hemorrhage
      was clinically silent and unsuspected. Among the clinically silent intracerebral
      hemorrhages, 22 measured less than 5 mm. 20 between 5 and 10 mm, five between 10
      and 30 mm, and four between 30 and 40 mm. Of the 55 patients with clinically
      silent hemorrhages, only three demonstrated a delayed neurological deficit (one
      case of seizure and two cases of progressive loss of consciousness) and these all
      occurred within the first 2 postoperative days. Of the neurologically well
      patients in whom no hemorrhage was demonstrated on initial postoperative CT scan,
      none experienced delayed deterioration. CONCLUSIONS: Clinically silent hemorrhage
      after stereotactic biopsy is very common. However, the authors did not find that
      knowledge of its existence ultimately affected individual patient management or
      outcome. The authors, therefore, suggest that the most important role of
      postoperative CT scanning is to screen for those neurologically well patients
      with no hemorrhage. These patients could safely be discharged on the same day
      they underwent biopsy.

PMID- 9647170
TI  - Multiple schwannomas: schwannomatosis or neurofibromatosis type 2?
AB  - OBJECT: The aim of this study was to clarify the clinical outcome of
      schwannomatosis, a rare condition characterized by multiple nonvestibular
      schwannomas in the absence of meningiomas, intraspinal ependymomas, and other
      clinical signs of neurofibromatosis type 2 (NF2). METHODS: Nine patients with
      schwannomatosis treated at one institution are presented and their clinical
      course during a median follow-up time of 9.9 years is discussed. The patients
      were typically middle-aged at the time of their first operation (median 43.5
      years), none had a positive family history of schwannomatosis or NF2, and none
      showed cutaneous or ocular signs of NF2. On histopathological examination the
      tumors from the patients with schwannomatosis showed a lobular appearance and
      frequent Verocay bodies, signs indicating NF2, more often than 20 sporadic
      schwannomas that were investigated as controls. Two patients died of unrelated
      causes at 3.2 and 9.9 years, respectively, of follow up. Magnetic resonance
      images of the head and spine were obtained in seven patients at the end of the
      follow-up period. New spinal schwannomas were detected in one patient and a
      residual schwannoma in three. No germline mutations of the NF2 gene were found in
      these seven patients. Two additional patients originally included in the
      schwannomatosis group who were 8.6 and 11.7 years old at initial surgery had NF2.
      One was diagnosed at follow-up review and the other developed a fulminant disease
      that led to death in 4 years. CONCLUSIONS: The clinical course, long-term
      outcome, and genetic mechanism of schwannomatosis differ from that of NF2.

PMID- 9647171
TI  - Systemic T cell adoptive immunotherapy of malignant gliomas.
AB  - OBJECT: To determine the feasibility, toxicity, and potential therapeutic
      benefits of systemic adoptive immunotherapy, 10 patients with progressive primary
      or recurrent malignant glioma received this treatment. Adoptive immunotherapy,
      the transfer of immune T lymphocytes, is capable of mediating the regression of
      experimental brain tumors in animal models. In animal models, lymph nodes (LNs)
      that drain the tumor vaccine site are a rich source of tumor-immune T cells.
      METHODS: In this clinical study, patients were inoculated intradermally with
      irradiated autologous tumor cells and granulocyte macrophage-colony stimulating
      factor as an adjuvant. Cells from draining inguinal LNs, surgically resected 7
      days after vaccination, were stimulated sequentially with staphylococcal
      enterotoxin A and anti-CD3, and a low dose of interleukin-2 (60 IU/ml) was used
      to expand the stimulated cells. The maximum cell proliferation was 350-fold over
      10 days of culture. The activated cells were virtually all T cells consisting of
      various proportions of CD4 and CD8 cells. These cells were given to patients by
      intravenous infusion at doses ranging from 9 x 10(8) to 1.5 x 10(11). There were
      no Grade 3 or 4 toxicities associated with the treatment. Following T-cell
      transfer therapy, radiographic regression that lasted at least 6 months was
      demonstrated in two patients with recurrent tumors. One patient demonstrated
      stable disease that has lasted for more than 17 months. The remaining patients
      had progressive disease; however, four of the eight patients with recurrent tumor
      remain alive more than 1 year after surgery for recurrence. Three patients
      required intervention with corticosteroid agents or additional surgery
      approximately 1 month following cell transfer. CONCLUSIONS: These intriguing
      clinical observations warrant further trials to determine whether this approach
      can provide therapeutic benefits and improve survival.

PMID- 9647172
TI  - Current neurosurgical management and the impact of the extent of resection in the
      treatment of malignant gliomas of childhood: a report of the Children's Cancer
      Group trial no. CCG-945.
AB  - OBJECT: One hundred seventy-two children with high-grade astrocytomas were
      treated by members of the Children's Cancer Group in a prospective randomized
      trial designed to evaluate the role of two chemotherapy regimens. Seventy-six
      percent of the patients (131 children) in whom a diagnosis of either anaplastic
      astrocytoma or glioblastoma multiforme was confirmed by central pathological
      review are the subject of this report. METHODS: Patients were stratified
      according to the extent of tumor resection (biopsy [< 10%], partial resection [10
      50%], subtotal resection [51-90%], near-total resection [> 90%], and total
      resection) as determined by surgical observation and postoperative computerized
      tomography scanning. Information on contemporary neurosurgical management was
      obtained from the patient's operative records and standardized neurosurgical
      report forms. The vast majority of tumors were supratentorial: 63% (83 tumors) in
      the superficial cerebral hemisphere, 28% (37 tumors) in the deep or midline
      cerebrum, and only 8% (11 tumors) in the posterior fossa. A significant
      association was detected between the primary tumor site and the extent of
      resection (p < 0.0001). A radical resection (> 90%) was performed in 37% of the
      children: 49% of the tumors in the superficial hemisphere and 45% of tumors in
      the posterior fossa compared with 8% of midline tumors. Tumor location could also
      be used to predict the need for both temporary and permanent cerebrospinal fluid
      (CSF) diversion. Half of the deep tumors and 8% of the hemispheric astrocytomas
      ultimately required a permanent CSF shunt. Improvement in preoperative
      neurological deficits and level of consciousness was seen in 36% and 34% of the
      children, respectively. New or increased deficits were present in 14% of the
      children, with 6% experiencing a diminished sensorium after surgery.
      Postoperative nonneurological complications were rare: infection, hematoma, and
      CSF fistula each occurred in 1.7% of the children. Univariate and multivariate
      analyses demonstrated that radical tumor resection (> 90%) was the only
      therapeutic variable that significantly improved progression-free survival (PFS)
      rates. For all patients with malignant astrocytomas, the distributions of PFS
      rates were significantly different (p = 0.006) following radical resection
      compared with less extensive (< or = 90%) resection. The 5-year PFS rates were 35
      +/- 7% and 17 +/- 4%, respectively. The differences in the distribution of PFS
      rate were significant for the subsets of patients with anaplastic astrocytoma (p
      = 0.055) and glioblastoma multiforme (p = 0.046). The 5-year PFS rates for
      anaplastic astrocytoma were 44 +/- 11% and 22 +/- 6% for cases in which the tumor
      was radically resected and less than radically resected, respectively; whereas
      the 5-year PFS rates for glioblastoma multiforme were 26 +/- 9% and 4 +/- 3% for
      cases in which the tumor was radically resected and less than radically resected,
      respectively. CONCLUSIONS: The demonstration of a survival advantage provided by
      radical resection should prompt neurosurgeons to treat malignant pediatric
      astrocytomas with aggressive surgical resection prior to initiation of
      radiotherapy or adjuvant chemotherapy.

PMID- 9647173
TI  - Dual-isotope single-photon emission computerized tomography scanning in patients
      with glioblastoma multiforme: association with patient survival and
      histopathological characteristics of tumor after high-dose radiotherapy.
AB  - OBJECT: The study was conducted to determine the association between dual-isotope
      single-photon emission computerized tomography (SPECT) scanning and
      histopathological findings of tumor recurrence and survival in patients treated
      with high-dose radiotherapy for glioblastoma multiforme. METHODS: Studies in
      which SPECT with 201Tl and 99mTc-hexamethypropyleneamine oxime (HMPAO) were used
      were performed 1 day before reoperation in 47 patients with glioblastoma
      multiforme who had previously been treated by surgery and high-dose radiotherapy.
      Maximum uptake of 201Tl in the lesion was expressed as a ratio to that in the
      contralateral scalp, and uptake of 99mTc-HMPAO was expressed as a ratio to that
      in the cerebellar cortex. Patients were stratified into groups based on the
      maximum radioisotope uptake values in their tumor beds. The significance of
      differences in patient gender, histological characteristics of tissue at
      reoperation, and SPECT uptake group with respect to 1-year survival was
      elucidated by using the chi-square statistic. Comparisons of patient ages and
      time to tumor recurrence as functions of 1-year survival were made using the t
      test. Survival data at 1 year were presented according to the Kaplan-Meier
      method, and the significance of potential differences was evaluated using the log
      rank method. The effects of different variables (tumor type, time to recurrence,
      and SPECT grouping) on long-term survival were evaluated using Cox proportional
      models that controlled for age and gender. All patients in Group I (201Tl ratio <
      2 and 99mTc-HMPAO ratio < 0.5) showed radiation changes in their biopsy
      specimens: they had an 83.3% 1-year survival rate. Group II patients (201Tl ratio
      < 2 and 99mTc-HMPAO ratio of > or = 0.5 or 201Tl ratio between 2 and 3.5
      regardless of 99mTc-HMPAO ratio) had predominantly infiltrating tumor (66.6%);
      they had a 29.2% 1-year survival rate. Almost all of the patients in Group III
      (201Tl ratio > 3.5 and 99mTc-HMPAO ratio > or = 0.5) had solid tumor (88.2%) and
      they had a 6.7% 1-year survival rate. Histological data were associated with 1
      year survival (p < 0.01): however, SPECT grouping was more closely associated
      with 1-year survival (p < 0.001) and was the only variable significantly
      associated with long-term survival (p < 0.005). CONCLUSIONS: Dual-isotope SPECT
      data correlate with histopathological findings made at reoperation and with
      survival in patients with malignant gliomas after surgical and high-dose
      radiation therapy.

PMID- 9647174
TI  - Symptomatic pituitary metastases.
AB  - OBJECT: The diagnosis and treatment of metastasis to the pituitary gland can be
      difficult to determine. The goal of this study was to analyze the clinical
      presentation, treatment, and prognosis of patients who presented with symptomatic
      pituitary metastasis. METHODS: The cases of 36 patients with symptomatic
      pituitary metastases were reviewed. The most common primary cancers were breast
      (33%) and lung (36%). The presenting symptoms included diabetes insipidus,
      anterior pituitary insufficiency, and retroorbital pain. The overall median
      length of patient survival following diagnosis of pituitary metastasis was 180
      days. In 20 patients (56%), symptoms stemming from pituitary metastasis were the
      first manifestation of illness. Local control of tumor was associated with
      significant improvement in survival times (p < 0.05) and amelioration of
      disabling symptoms including painful ophthalmoplegia and visual field deficits.
      CONCLUSIONS: Aggressive treatment including both surgical decompression and
      radiation therapy improves the quality of life in patients suffering from
      symptomatic pituitary metastasis.

PMID- 9647175
TI  - Endovascular treatment of mural-type vein of Galen malformations.
AB  - OBJECT: In this study the authors report on the results of endovascular treatment
      for mural-type vein of Galen malformations (VGMs) in a group of infants. METHODS:
      Eight children (six infants and two neonates) who suffered from symptoms caused
      by a mural-type VGM were treated by means of endovascular therapy. Their age at
      the time of treatment ranged from 13 days to 19 months (mean 7.6 months). Two
      neonates and three infants who presented with hydrocephalus and increased head
      circumference, one of whom was stabilized with a shunt, underwent elective
      closure of the malformations 3, 4, 6, 6, and 13 months later, respectively. Two
      patients presented with hemorrhage; one had an intraventricular hemorrhage (IVH)
      on the 1st day of life and one, a 5-month-old infant, suffered a large
      parenchymal hemorrhage and an IVH; both patients were immediately cured by means
      of endovascular techniques. One child presented with a seizure and cortical
      venous drainage that were treated immediately. Eleven separate treatment sessions
      were conducted; eight via transarterial femoral access and the remaining three
      via a transvenous approach. Two patients were treated by using transfemoral
      transvenous embolization with fibered coils, and one patient required a
      transtorcular transvenous approach to permit complete closure of the fistula with
      electrolytically detachable coils. The embolic devices used included silk suture
      emboli (three patients), electrolytically detachable coils (three patients), and
      fibered platinum coils (seven patients). In seven patients, complete closure was
      demonstrated on postembolization arteriographic studies. The eighth patient had
      stagnant flow in a giant 6-cm varix treated with arterial and venous coils but
      has not yet undergone follow-up studies. Late follow-up arteriography was
      performed in four patients at times ranging from 11 to 24 months postprocedure.
      In one patient, thrombosis of the malformation and shrinkage of the varix were
      confirmed on follow-up computerized tomography scanning. The remaining three
      patients have not yet undergone follow-up angiographic examination. Two
      asymptomatic complications occurred, including separation of the distal catheter,
      which was removed with a snare device, and a single platinum coil that embolized
      to the lung, producing no symptoms in 101 months of clinical follow up. The
      follow-up period ranged from 3 to 105 months, with a mean of 52 months.
      CONCLUSIONS: Endovascular therapy is the treatment of choice for mural-type VGMs
      and offers a high rate of cure with low morbidity.

PMID- 9647176
TI  - Endovascular embolization of 150 basilar tip aneurysms with Guglielmi detachable
      coils: results of the Food and Drug Administration multicenter clinical trial.
AB  - OBJECT: To assess the safety and efficacy of aneurysm embolization performed
      using Guglielmi detachable coils (GDCs), the authors reviewed the results of a
      cohort of 150 patients with either ruptured (83 patients) or unruptured (67
      patients) basilar tip aneurysms treated with these detachable platinum coil
      devices in the early part of the United States multicenter GDC clinical trial
      that led to Food and Drug Administration approval for the device. METHODS: The
      most common presentation in this cohort of patients was headache (53%). All
      patients were entered into the trial after neurosurgical assessment excluded them
      as candidates for surgical clipping of their aneurysms. Greater than 90% coil
      packing was achieved in 75% of the patients. For those patients in whom follow-up
      information was available, the mean angiographic and clinical evaluation follow
      up time for 61 patients with ruptured aneurysms was 13.7 months (range 0-43
      months) and that for the 49 patients with unruptured aneurysms was 9.8 (range 0
      40 months). Conservative mortality rates included up to 23% for the ruptured
      aneurysm group and up to 12% for the unruptured aneurysm group; the rebleeding
      rate for treated ruptured aneurysms was up to 3.3% and the bleeding rate for
      unruptured aneurysms up to 4.1%. Permanent deficits due to stroke in patients
      with ruptured or unruptured aneurysms occurred in up to 5% and 9%, respectively.
      Vasospasm occurred in 8% of the patients; it was associated with two deaths.
      Periprocedural mortality was 2.7% (four patients with ruptured aneurysms).
      CONCLUSIONS: Detachable platinum coil embolization is a promising treatment for
      ruptured basilar tip aneurysms that are not surgically clippable; in selected
      patients it offers lower incidences of morbidity and mortality compared with
      conservative medical management. The role of this procedure in unruptured basilar
      tip aneurysms is unclear with less supportive results. More long-term follow-up
      evaluation is necessary and results are expected to improve.

PMID- 9647177
TI  - Causes and management of aneurysmal hemorrhage occurring during embolization with
      Guglielmi detachable coils.
AB  - OBJECT: The purpose of this review is to describe the incidence, causes,
      management, and outcome of aneurysmal hemorrhage that occurred in patients during
      endovascular treatment with the Guglielmi detachable coil (GDC) system. METHODS:
      At the authors' institution between September 1991 and August 1995, more than 200
      patients were treated using GDCs for intracranial aneurysms. The first 200
      patients treated in this fashion were reviewed and all who experienced new
      subarachnoid hemorrhage (SAH) during the procedure were identified. Angiographic
      studies were also reviewed and patients were contacted for longer-term follow up
      when possible. Four patients who experienced intraprocedural SAH were identified.
      The causes of hemorrhage were believed to be perforation of the aneurysm by the
      guidewire in one patient, perforation by the microcatheter in a second, and
      perforation by the delivery wire in a third. The fourth patient had a hemorrhage
      during injection of contrast material for control angiographic studies after
      placement of the final coil. One patient died, but the other three experienced no
      neurological symptoms or recovered without acquiring additional deficits. Overall
      a procedural hemorrhage rate of 2% was seen, with permanent morbidity and
      mortality rates of 0% and 0.5%, respectively. CONCLUSIONS: Although SAH during
      endovascular treatment of intracranial aneurysms remains a significant risk, its
      incidence is low and a majority of patients can survive without serious sequelae.

PMID- 9647178
TI  - Improvement of cerebral oxygenation patterns and metabolic validation of
      superselective intraarterial infusion of papaverine for the treatment of cerebral
      vasospasm.
AB  - OBJECT: The purpose of the present study was to assess cerebral oxygenation
      patterns and brain lactate concentration changes before, during, and after
      intraarterial infusion of papaverine with or without balloon angioplasty in
      patients with symptomatic vasospasm. METHODS: A total of 23 vascular territories
      were successfully treated in 10 patients. In three patients balloon angioplasty
      was performed before the papaverine infusion. Continuous monitoring of jugular
      bulb vein oxygen saturation with a fiberoptic catheter and blood sampling allowed
      the assessment of the cerebral arteriovenous oxygen and lactate differences. A
      significant and rapid improvement in jugular bulb oxygen saturation was observed
      in all cases, with critical values reflecting an improvement in cerebral
      oxygenation after endovascular treatment of vasospasm (p = 0.005). Lactate
      concentration in the jugular bulb normalized within 4 hours in all patients who
      had evidence of brain lactic acidosis before superselective intraarterial
      infusion of papaverine. Recurrence of abnormal metabolic and oxygenation patterns
      were observed in one case in which an optimal hypertension and hypervolemic
      therapy could not be achieved after the procedure. CONCLUSIONS: Improvement in
      cerebral oxygenation as well as prevention of cerebral lactic acidosis can be
      successfully achieved after intraarterial infusion of papaverine. Normalization
      of the oxygen supply after endovascular treatment has to be supported by optimal
      and well-monitored hypertension and hypervolemic hemodilution.

PMID- 9647179
TI  - Seasonal pattern of spontaneous cervical artery dissection.
AB  - OBJECT: The etiology of spontaneous cervical artery dissection is poorly
      understood; however, it may involve genetic and environmental factors. The
      purpose of this study was to determine whether seasonality of spontaneous
      cervical artery dissection exists. METHODS: The seasonal pattern of spontaneous
      cervical artery dissection was analyzed in a group of 200 consecutive patients
      (104 females and 96 males with a mean age of 44.9 years) who were evaluated using
      the Rayleigh test during the period from 1970 to 1990. The majority of patients
      resided in the midwestern section of the United States, where large seasonal
      fluctuations in climate occur. A circannual periodicity was found in the
      frequency of spontaneous cervical artery dissections with a peak occurring in
      October (p < 0.02). The seasonal variation was substantial, with approximately
      58% more patients suffering a cervical artery dissection during autumn than
      during other seasons. CONCLUSIONS: A seasonal pattern of spontaneous cervical
      artery dissection exists with a peak occurring in October. The cause of the
      seasonality remains to be explained; however, weather- or infectious disease
      related factors may provide etiological leads.

PMID- 9647180
TI  - Analysis of treatment failure after radiosurgery for arteriovenous malformations.
AB  - OBJECT: The aim of this study was to evaluate the causes of treatment failure in
      patients with arteriovenous malformations (AVMs) who underwent radiosurgery,
      which is increasingly used as a treatment method for selected, surgically high
      risk AVMs. Unfortunately, radiosurgical treatment fails in a small but
      significant percentage of patients. In the time period covered in this study, 72
      patients attained angiographically confirmed cures after radiosurgery and 36 were
      retreated after the initial radiosurgical treatment failed. METHODS: Using a
      computerized image fusion technique, the initial radiosurgical dosimetry plan was
      superimposed on the remaining AVM nidus at the time of retreatment. Twenty-six
      percent of the retreated cases were found to have AVM niduses outside the
      original treatment isodose line, which means that targeting error was a factor.
      The retreated group was also statistically compared with the cured group.
      CONCLUSIONS: Multivariate analysis revealed that the following factors were
      statistically significant predictors of treatment failure: increasing AVM size,
      decreasing treatment dose, and increasing Spetzler-Martin grade.

PMID- 9647181
TI  - The effect of subarachnoid hemorrhage on mechanisms of vasodilation mediated by
      cyclic adenosine monophosphate.
AB  - OBJECT: This study was designed to determine whether subarachnoid hemorrhage
      (SAH) affects the function of the K+ channels responsible for relaxation of
      canine cerebral arteries in response to adenylate cyclase activation. METHOD: The
      effect of K+ channel inhibitors on the arterial relaxation response to forskolin,
      a direct adenylate cyclase activator, was studied in rings of basilar arteries
      obtained from normal dogs and dogs in which SAH was induced (double-hemorrhage
      model). The levels of adenosine 3',5'-cyclic monophosphate (cAMP) were measured
      using the radioimmunoassay technique. In rings with the endothelium removed,
      relaxation induced by forskolin was not affected by SAH. The relaxation response
      to forskolin was reduced by charybdotoxin (10(-7) mol/L), a selective Ca++
      activated K+ channel inhibitor, in normal arteries and arteries subjected to
      autologous blood injection. This inhibitory effect of charybdotoxin was
      significantly greater in arteries involved in SAH than in normal vessels. The
      relaxation response to forskolin was reduced by 4-aminopyridine (10(-3) mol/L), a
      delayed rectifier K+ channel inhibitor, only in arteries involved in SAH. In
      contrast, the relaxation response to forskolin was not affected by glyburide (10(
      5) mol/L), an adenosine 5'-triphosphate-sensitive K+ channel inhibitor, in both
      normal and SAH arteries. Forskolin (3 x 10(-7) mol/L) produced an approximately
      10-fold increase in levels of cAMP. The basal values and increased levels of cAMP
      detected after stimulation with forskolin were no different in normal arteries
      and those exposed to SAH. CONCLUSIONS: These results demonstrate that formation
      of cAMP and the relaxation response to adenylate cyclase activation are not
      affected by SAH. However, in diseased arteries, K+ channels assume a more
      important role in the mediation of relaxation response to forskolin, indicating
      that SAH may change the mechanisms responsible for vasodilation induced by cAMP.

PMID- 9647182
TI  - Local cerebral blood flow autoregulation following "asymptomatic" cerebral venous
      occlusion in the rat.
AB  - OBJECT: Maintenance of cerebral blood flow (CBF) autoregulation in the brain is
      of major importance for patient outcome in various clinical conditions. The
      authors assessed local autoregulation after "asymptomatic" cortical vein
      occlusion. METHODS: In Wistar rats, a single cortical vein was occluded
      photochemically by using rose bengal and fiberoptic illumination. In rats with
      bilateral carotid artery occlusion, mean arterial blood pressure (MABP) was
      lowered in 5-mm Hg increments down to 40 mm Hg by using hypobaric hypotension.
      Local CBF at each pressure level was assessed by performing laser Doppler (LD)
      scanning at 25 (5 x 5) locations within bilateral cranial windows. In this
      manner, the lower limit of autoregulation (LLA) was detected. The LLA was 60 mm
      Hg in both right and left hemispheres in Group A (five rats), in which the
      animals received illumination without rose bengal and had no venous occlusion. Of
      the 11 rats that underwent vein occlusion, three developed severe reductions in
      local CBF and/or a growing venous thrombus and were distinguished as Group C
      (symptomatic; three rats); from previous work we know that those animals are
      bound to experience venous infarction. The remaining rats formed Group B
      (asymptomatic; eight rats). In this group the LLA remained at 60 mm Hg in the
      left hemisphere without occlusion, whereas, in the right cortex with the occluded
      vein, the LLA was found to be 65 mm Hg. Below a carotid stump pressure of 25 mm
      Hg regional CBF in the affected hemisphere dropped more abruptly to a possibly
      ischemic range than that in the opposite normal hemisphere. CONCLUSIONS: The
      results of the present study suggest that cerebral venous circulation disorders
      are manifested via additional pathways, that is, from a partially impaired local
      autoregulation in the vicinity of the occluded vein, even under conditions in
      which the vein occlusion itself does not cause brain damage. Care should be taken
      in the control of blood pressure in patients with this pathological condition.

PMID- 9647183
TI  - Enhancement of radiosensitivity of wild-type p53 human glioma cells by adenovirus
      mediated delivery of the p53 gene.
AB  - OBJECT: The authors sought to determine whether combining p53 gene transfer with
      radiation therapy would enhance the therapeutic killing of p53 wild-type glioma
      cells. It has been shown in several reports that adenovirus-mediated delivery of
      the p53 gene into p53 mutant gliomas results in dramatic apoptosis, but has
      little effect on gliomas containing wild-type p53 alleles. Therefore, p53 gene
      therapy alone may not be a clinically effective treatment for gliomas because
      most gliomas are composed of both p53 mutant and wild-type cell populations. One
      potential approach to overcome this problem is to exploit the role p53 plays as
      an important determinant in the cellular response to ionizing radiation. METHODS:
      In vitro experiments were performed using the glioma cell line U87MG, which
      contains wild-type p53. Comparisons were made to the glioma cell line U251MG,
      which contains a mutant p53 allele. Monolayer cultures were infected with an
      adenovirus containing wild-type p53 (Ad5CMV-p53), a control vector (dl312), or
      Dulbecco's modified Eagle's medium (DMEM). Two days later, cultures were
      irradiated and colony-forming efficiency was determined. Transfection with p53
      had only a minor effect on the plating efficiency of nonirradiated U87MG cells,
      reducing the plating efficiency from 0.23 +/- 0.01 in DMEM to 0.22 +/- 0.04 after
      addition of Ad5CMV-p53. However, p53 transfection significantly enhanced the
      radiosensitivity of these cells. The dose enhancement factor at a surviving
      fraction of 0.10 was 1.5, and the surviving fraction at 2 Gy was reduced from
      0.61 in untransfected controls to 0.38 in p53-transfected cells. Transfection of
      the viral vector control (dl312) had no effect on U87MG radiosensitivity. In
      comparison, transfection of Ad5CMV-p53 into the p53 mutant cell line U251 MG
      resulted in a significant decrease in the surviving fraction of these cells
      compared with controls, and no radiosensitization was detected. To determine
      whether Ad5CMV-p53-mediated radiosensitization of U87MG cells involved an
      increase in the propensity of these cells to undergo apoptosis, flow cytometric
      analysis of terminal deoxynucleotidyl transferase-mediated biotinylated
      deoxyuridinetriphosphate nick-end labeling-stained cells was performed. Whereas
      the amount of radiation-induced apoptosis in uninfected and dl312-infected
      control cells was relatively small (2.1 +/- 0.05% and 3.7 +/- 0.5%,
      respectively), the combination of Ad5CMV-p53 infection and radiation treatment
      significantly increased the apoptotic frequency (18.6 +/- 1.4%). To determine
      whether infection with Ad5CMV-p53 resulted in increased expression of functional
      exogenous p53 protein, Western blot analysis of p53 was performed on U87MG cells
      that were exposed to 9 Gy of radiation 2 days after exposure to Ad5CMV-p53,
      dl312, or DMEM. Infection with Ad5CMV-p53 alone increased p53 levels compared
      with DMEM- or dl312-treated cells. Irradiation of AdSCMV-p53-infected cells
      resulted in a further increase in p53 that reached a maximum at 2 hours
      postirradiation. To determine whether exogenous p53 provided by Ad5CMV-p53 had
      transactivating activity, U87MG cells were treated as described earlier and p21
      messenger RNA levels were determined. Infection of U87MG cells with Ad5CMV-p53
      only resulted in an increase in p21 compared with DMEM- and dl312-treated cells.
      Irradiation of AdSCMV-p53-infected cells resulted in an additional time-dependent
      increase in p21 expression. CONCLUSIONS: These data indicate that adenovirus
      mediated delivery of p53 may enhance the radioresponse of brain tumor cells
      containing wild-type p53 and that this radiosensitization may involve converting
      from a clonogenic to the more sensitive apoptotic form of cell death. Although
      the mechanism underlying this enhanced apoptotic susceptibility is unknown, the
      AdSCMV-p53-infected cells have a higher level of p53 protein, which increases
      further after irradiation, and this exogenous p53 is transcriptionally active.
      (ABSTRACT TRUNCATE

PMID- 9647184
TI  - Ninety-degree rotation of the thoracic spinal thecal sac. Case report.
AB  - This 44-year-old man presented with a 4-year history of progressive spastic
      weakness of his legs. He was found to have epidural lipomatosis behind the
      thoracic spinal cord, and the nerve roots exited from the posterior and anterior
      midline planes of the dura, indicating a 90 degree rotation of the thoracic cord.
      Magnetic resonance images clearly demonstrated the segmental thoracic nerve roots
      exiting from the dorsal midline of the dura, a finding confirmed at surgery. The
      authors found only one previously published case of rotation of the spinal cord.
      Directed mechanical stress caused by deformation of the rotated spinal cord,
      rather than compression from adipose tissue, is proposed as the mechanism of the
      myelopathy. The extent, location, and thickness of the associated extradural
      adipose tissue is suggestive of epidural lipomatosis. The lipomatous tissue might
      have been an epiphenomenon and cord rotation an isolated congenital anomaly.
      Alternatively, asymmetrical growth of epidural fat may have exerted torque,
      rotating the thecal sac.

PMID- 9647185
TI  - Familial cervical spondylosis. Case report.
AB  - Cervical spondylosis is a disease that is often attributed to aging and
      considered the result of degenerative changes in the spine. The idea that there
      is a genetic predisposition to develop diseases of the skeletal elements of the
      spine has been discussed previously, but has never been proven conclusively. The
      authors report three cases of severe cervical spondylosis in patients who are
      first-degree relatives: a mother and her two sons. All three individuals had
      cervical disc herniations and stenosis at C3-4, C4-5, C5-6, and C6-7, and all
      three required decompressive procedures. The location and degree of cervical
      spondylosis were as similar among these three patients as they have been in
      identical twins reported in other studies. Such familial inheritance of cervical
      spondylosis has been reported only once. The existence of familial cervical
      spondylosis is not an unrealistic proposal because other studies have shown that
      genetics determines the shape of one's spine and that similar spines tend to
      degenerate in similar ways. Therefore, genetic counseling for a family such as
      the one reported here may prove to be of great benefit to warn siblings that they
      are at high risk for cervical spine injury. However rare it might be, familial
      cervical spondylosis may be a phenomenon that any spine surgeon should suspect in
      a family with cervical spine abnormalities found in several members.

PMID- 9647186
TI  - Delayed aneurysm regrowth and recanalization after Guglielmi detachable coil
      treatment. Case report.
AB  - Guglielmi detachable coil (GDC) treatment for complicated cerebral aneurysms is
      an attractive option that has become widely accepted in recent years. This
      technique is usually considered only if the patient harbors an aneurysm that is
      not a good candidate for surgical clipping. However, the definition of "surgical
      candidate" varies among institutions, and many patients worldwide are being
      treated with GDCs as primary therapy. Although most centers currently perform
      follow-up angiography at 6 months to 1 year, others do not routinely perform it
      after an initially good result. The authors present a case that indicates longer
      follow up may be necessary and illustrates some of the pitfalls of GDC treatment.
      This 56-year-old man presented to the emergency room with a Hunt and Hess Grade
      II subarachnoid hemorrhage and was found to have a wide-necked basilar apex
      aneurysm. Because of associated medical comorbidities, it was decided to treat
      the aneurysm with endovascular techniques. The patient did well on follow-up
      angiography at 1 year postprocedure. However, at approximately 2 years follow up,
      the aneurysm was demonstrated to have dramatically recanalized and regrown,
      requiring open surgical intervention. Endovascular coiling was insufficient to
      treat this aneurysm and complicated definitive surgical management because a
      large coil mass had been placed in the operative field. It can be inferred from
      this case that angiographic follow up of these types of lesions may be beneficial
      up to 2 years after GDC treatment.

PMID- 9647187
TI  - Suprasellar tension pneumocyst after transsphenoidal surgery. Case report.
AB  - Tension pneumocephalus is an uncommon occurrence after transsphenoidal surgery.
      The author presents an unusual case of postoperative visual deterioration related
      to expanding air within a suprasellar tumor cavity.

PMID- 9647188
TI  - Neurofibromatosis type 2: growth stimulation of mixed acoustic schwannoma by
      concurrent adjacent meningioma: possible role of growth factors. Case report.
AB  - The authors report the case of a young man suffering from neurofibromatosis type
      2 (NF2) who harbored bilateral acoustic schwannomas and a parasellar meningioma.
      Neuroimaging studies performed during a 4-year follow-up period showed that the
      bilateral schwannomas had grown very little and at similar rates. However, after
      the meningioma had infiltrated the tentorium and approached the ipsilateral
      schwannoma at the incisura, both Schwann cell tumors started to grow rapidly,
      particularly the one adjacent to the meningioma, of which the percentage of
      annual growth rate increased by approximately a factor of 10(2). At the same
      time, magnetic resonance imaging showed that this tumor also changed its
      features. During surgery, the acoustic schwannoma was firmly adherent to both
      meningioma and tentorium. Histological examination revealed meningotheliomatous
      cells in the schwannoma adjacent to the meningioma. Antiphosphotyrosine
      immunoblotting of PC12 cells was compatible with the presence of an epidermal
      growth factor (EGF)-like molecule in the cerebrospinal fluid (CSF) of the
      patient. This factor was not detected in the CSF of five other NF2 patients, two
      of whom bore associated bilateral acoustic schwannomas and meningioma in remote
      locations. It is hypothesized that the meningotheliomatous cells infiltrating the
      schwannoma triggered an autocrine/paracrine growth-stimulatory mechanism that
      involved an EGF-like factor.

PMID- 9647189
TI  - Use of ligamentum nuchae graft for dural closure in posterior fossa surgery.
      Technical note.
AB  - The technique of harvesting the ligamentum nuchae and its use in posterior fossa
      surgery are discussed. By using this technique the author has avoided
      postoperative cerebrospinal fluid leakage in more than 200 procedures.

PMID- 9647190
TI  - Posterior ventricular catheter burr-hole localizer. Technical note.
AB  - Proper ventricular catheter placements are associated with improved shunt
      performance. When placing ventricular catheters via the posterior approach, the
      surgeon must determine an optimum trajectory and then pass a catheter along that
      trajectory. The incidence of optimal posterior catheter placements is increased
      by using a posterior catheter guide (PCG); however, errors may still occur
      because of poor selection of a posterior burr-hole site. In this report an easy
      to-use posterior burr-hole localizer (Localizer) is described that defines the
      optimum burr-hole location based on geometric relationships involving the ear and
      supraorbital rims. The basic design principle of the Localizer was formulated and
      tested by using neuronavigational imaging tools to examine normal adult
      ventricular anatomy in relation to surface landmarks and by reviewing imaging
      studies obtained in 50 adult patients with hydrocephalus. Subsequently, the
      Localizer was used in 28 consecutive patients scheduled to undergo shunt surgery
      performed by using the PCG. In all cases the catheter entered the ventricle on
      the first pass and postoperative imaging studies demonstrated successful
      placement in the ipsilateral anterior horn. There were no catheter-related
      complications. These early results indicate that the Localizer and PCG devices
      may be safe and effective when used in combination for placement of posterior
      ventricular catheters.

PMID- 9647191
TI  - Giant nasal schwannoma with intracranial extension. Case illustration.

PMID- 9647192
TI  - Tumor growth rates.

PMID- 9647193
TI  - Radiation-induced cavernous malformation.

PMID- 9647194
TI  - Medullary compression and hypertension.

PMID- 9647195
TI  - Arteriovenous malformations after radiosurgery.

PMID- 9647196
TI  - Arteriovenous malformations after radiosurgery.

PMID- 9647197
TI  - Meningeal melanocytoma.

PMID- 9647198
TI  - Intraventricular chemotherapy.

PMID- 9647199
TI  - TRANK, a novel cytokine that activates NF-kappa B and c-Jun N-terminal kinase.
AB  - We searched the expressed sequence tag database using sequence homology and
      identified a novel cytokine, which we have named TRANK (thioredoxin peroxidase
      related activator of NF-kappa B and c-Jun N-terminal kinase). The predicted amino
      acid sequence of TRANK was highly homologous to that of the thiol-specific
      antioxidant proteins. Unlike these proteins, however, TRANK had a putative
      secretory signal polypeptide and was found to be secreted by cells. TRANK was
      expressed in most tissues and cell lines, and the gene that encodes it was mapped
      to chromosome Xp21-22.1. TRANK activated NF-kappa B and induced the degradation
      of the inhibitory subunit of NF-kappa B. In addition, TRANK up-regulated the
      expression of NF-kappa B-dependent gene products, ICAM-1, and inducible nitric
      oxide synthase. TRANK also activated c-Jun N-terminal kinase and induced the
      proliferation of normal human foreskin fibroblasts. Its homology with antioxidant
      proteins, wide distribution in tissues, and ability to activate NF-kappa B and c
      Jun N-terminal kinase suggest that TRANK plays an important role in inflammation.

PMID- 9647200
TI  - Ly-49D and Ly-49H associate with mouse DAP12 and form activating receptors.
AB  - Several members of the Ly-49 receptor family inhibit NK cell-mediated lysis of
      targets expressing appropriate MHC class I molecules. Ly-49D and Ly-49H, two Ly
      49 molecules that lack immunoreceptor tyrosine-based inhibitory motifs (ITIM) in
      their cytoplasmic domains, associate with mouse DAP12, a molecule that possesses
      an immunoreceptor tyrosine-based activation motif (ITAM). Cotransfection of
      either Ly-49D or Ly-49H with DAP12 induces surface expression of both Ly-49 and
      DAP12. The Ly-49/DAP12 complex was coimmunoprecipitated from the transfected
      cells, demonstrating a physical association of DAP12 with Ly-49D or Ly-49H in the
      plasma membrane. Stimulation of transfectants with Abs recognizing either Ly-49D
      or Ly-49H results in cellular activation, as assessed by induction of tyrosine
      phosphorylation of multiple cellular substrates.

PMID- 9647201
TI  - The expression in vivo of a second isoform of pT alpha: implications for the
      mechanism of pT alpha action.
AB  - A second isoform of pT alpha, "pT alpha(b)," is derived from the pT alpha locus
      by tissue-specific, alternative splicing. pT alpha(b) is coexpressed in the
      thymus with the previously characterized form of pT alpha (which we term pT
      alpha(a)) and is also expressed in peripheral cells without pT alpha(a). While pT
      alpha(a) acts to retain most TCR beta-chains intracellularly, pT alpha(b) permits
      higher levels of cell surface TCR beta expression and facilitates signaling from
      a CD3-TCR beta complex.

PMID- 9647202
TI  - Differences in the immune response during the acute phase of E-55+ murine
      leukemia virus infection in progressor BALB and long term nonprogressor C57BL
      mice.
AB  - E-55+ murine leukemia virus infection of both progressor (BALB) and long term
      nonprogressor (C57BL) mouse strains is characterized by an acute and a persistent
      phase of infection. During the acute phase, progressor strains require CD8+ T
      cells to decrease virus burden, whereas the long term nonprogressor strains do
      not. In the present studies the immune response in BALB and C57BL mice during the
      acute phase of E-55+ murine leukemia virus infection was examined. The results
      demonstrate that BALB mice produce both IL-4 and IFN-gamma, in contrast to C57BL
      mice, which produce only IFN-gamma. In BALB mice, IL-4 production results in the
      absolute requirement for CD8+ T cells to reduce the virus burden during the acute
      phase of infection. The anti-virus immune response in these mice is IFN-gamma
      dependent. On the other hand, C57BL mice do not produce IL-4 and, in the absence
      of both CD8+ T cells and IFN-gamma, still generate an effective anti-virus immune
      response. Genetic studies suggest that these distinct immune responses are
      regulated by more than one non-MHC-linked gene. Two candidate regions that may
      encode this gene(s), located on chromosomes 7 and 19, respectively, were
      identified by recombinant inbred strain linkage analysis.

PMID- 9647203
TI  - The role of estrogen receptors and androgen receptors in sex steroid regulation
      of B lymphopoiesis.
AB  - Several observations suggest that sex steroids might participate in steady state
      regulation of B lymphopoiesis. B cell precursors decline dramatically in bone
      marrow of pregnant or estrogen-treated mice. Reciprocally, the same cell
      populations are increased in hypogonadal mice or male castrates. Estrogen
      treatment of hypogonadal mice reduced precursors to normal. However, questions
      remain about which hormones and receptors are the most important. Furthermore,
      these observations need to be reconciled with advances regarding new sex steroid
      receptors. We have now characterized B lymphopoiesis in androgen receptor
      deficient testicular feminization (Tfm) mice. Testicular feminization mice had
      substantially elevated numbers of B cell precursors in the bone marrow and B
      cells in the spleen as compared with wild-type mice. The importance of one
      estrogen receptor (ER alpha) was evaluated in gene-targeted mice, and B cell
      precursors were found to be within the normal range. Our previous studies
      indicated that hormone receptors in stromal cells may be important for estrogen
      mediated suppression of B lymphopoiesis. We now show that estrogen-mediated
      inhibition of B cell precursor expansion in culture was blocked by a specific
      estrogen receptor antagonist (ICI 182,780). Stromal cells derived from ER alpha
      targeted bone marrow were fully estrogen responsive. RT-PCR analyses of these
      stromal cells revealed splice-variant transcripts of ER alpha, as well as message
      for a recently discovered estrogen-binding receptor, ER beta. Thus, androgens may
      normally inhibit B lymphopoiesis through the androgen receptor, whereas estrogens
      might utilize one or more receptors to achieve the same physiologic response.

PMID- 9647204
TI  - Proteasome activation occurs at an early, premitochondrial step of thymocyte
      apoptosis.
AB  - Proteasomes and mitochondrial membrane changes are involved in thymocyte
      apoptosis. The hierarchical relationship between protease activation and
      mitochondrial alterations has been elusive. Here we show that inhibition of
      proteasomes by two specific agents, lactacystin or MG132, prevents all
      manifestations of thymocyte apoptosis induced by the glucocorticoid receptor
      agonist dexamethasone or by the topoisomerase II inhibitor etoposide. Lactacystin
      and MG132 prevent the early disruption of the mitochondrial transmembrane
      potential (delta psi(m)), which precedes caspase activation, exposure of
      phosphatidylserine, and nuclear DNA fragmentation. In contrast, stabilization of
      the delta psi(m) using the permeability transition pore inhibitor bongkrekic acid
      or inhibition of caspases by N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone
      does not prevent the activation of proteasomes, as determined with the
      fluorogenic substrate N-succinyl-L-leucyl-L-leucyl-L-valyl-L-tyrosine-7-amido-4
      methylcoumarin . Thus, proteasome activation occurs upstream from mitochondrial
      changes and caspase activation. Whereas the proteasome-specific agents
      lactacystin and MG132 truly maintain thymocyte viability, a number of protease
      inhibitors that inhibit nuclear DNA fragmentation (acetyl-Asp-Glu-Val-Asp
      fluoromethylketone; N-Boc-Asp(OMe)-fluoromethylketone; N-tosyl-L-Phe
      chloromethylketone) do not prevent the cytolysis induced by DEX or etoposide.
      These latter agents fail to interfere with the preapoptotic delta psi(m)
      disruption. Altogether, our data indicate that different proteases may be
      involved in the pre- or postmitochondrial phase of apoptosis. Only those protease
      inhibitors that interrupt the apoptotic process at the premitochondrial stage can
      actually preserve cell viability.

PMID- 9647205
TI  - Repertoire analysis of CD8+ T cell responses to minor histocompatibility antigens
      involved in graft-versus-host disease.
AB  - Graft-vs-host disease (GVHD) is a major complication of allogeneic bone marrow
      transplantation. Experimentally, lethal GVHD can be induced in MHC-matched strain
      combinations differing in expression of multiple minor histocompatibility Ags
      (miHA). Recently, the GVHD potential of C57BL/6By (B6) T cells in irradiated
      BALB.B (both H2b) and related CXB recombinant inbred strains of mice has been
      studied to determine the scope of the response to miHA in vivo and how it
      compared with CTL responses to immunodominant miHA in vitro. The GVHD response in
      these strain combinations appeared to be limited to a few Ags, yet there was no
      correlation of these miHA with that of in vitro CTL responses. To further
      investigate the role of CD8+ T cells in GVHD, we analyzed positively selected
      miHA-specific donor CD8+ thoracic duct lymphocytes (TDL) collected from
      irradiated BALB.B and CXBE mice, 5 to 6 days after transplantation of B6 T cells.
      Flow cytometric analysis of B6-->BALB.B TDL did not indicate expansion of any
      particular TCR Vbeta family, whereas Vbeta10 and Vbeta14 families were
      significantly expanded in the B6-->CXBE TDL. However, PCR-based complementarity
      determining region 3 size spectratyping revealed overlapping involvement of donor
      Vbeta1, 6, 8, 9, 10, and 14 families in both BALB.B and CXBE recipients and
      unique utilization of the Vbeta4 family in BALB.B mice, suggesting oligoclonal T
      cell responses to a limited number of miHA. In addition, the injection of CD8+
      Vbeta14+ B6 T cells into irradiated BALB.B and CXBE mice induced lethal GVHD,
      confirming the involvement of miHA-specific T cells within an individual Vbeta
      family.

PMID- 9647206
TI  - Requirements for B7-CD28 costimulation in mucosal IgA responses: paradoxes
      observed in CTLA4-H gamma 1 transgenic mice.
AB  - The block in the CD80/CD86-CD28/CTLA-4 pathway in CTLA4-H gamma 1 transgenic (Tg)
      mice results in strongly impaired systemic IgG immunity and failure to develop
      germinal center reactions. By contrast, here we report that mucosal immunity and
      IgA B cell differentiation are not affected by this block. We found abundant
      germinal centers and evidence of IgA switch differentiation in Peyer's patches,
      normal total IgA levels, and normal numbers of IgA-labeling cells in the gut
      mucosa. The distribution of B-1 and B-2 cells and the relative contribution of B
      1 cells to the total IgA B cells were similar in Tg and wild-type mice. Despite
      this, oral immunizations with keyhole limpet hemocyanin plus cholera toxin
      adjuvant failed to stimulate Ag-specific mucosal IgA responses in CTLA4-H gamma 1
      Tg mice. This was not due to a lack of adjuvant activity of cholera toxin in Tg
      mice, nor was this secondary to an inability to take up Ag from the gut lumen.
      Rather, CD4+ T cells stimulated by oral immunization in Tg mice appeared to be
      inappropriately primed, as evidenced by a significantly reduced level of CD40
      ligand and CD44 expression and an increased expression of CD95 compared to those
      in wild-type mice. This study reveals a paradox in the regulation of mucosal IgA
      responses.

PMID- 9647207
TI  - A viral peptide with limited homology to a self peptide can induce clinical signs
      of experimental autoimmune encephalomyelitis.
AB  - Molecular mimicry has been suggested as a mode of autoreactive T cell stimulation
      in autoimmune diseases. Myelin basic protein (MBP) peptide 1-11 induces
      experimental autoimmune encephalomyelitis (EAE) in susceptible strains of mice.
      Here we show that a herpesvirus Saimiri (HVS) peptide, AAQRRPSRPFA, with a
      limited homology to MBP1-11 peptide, ASQKRPSQRHG (underlined letters showing
      homology), can stimulate a panel of MBP-11-specific T cell hybridomas and more
      importantly cause EAE in mice. We demonstrate that this is due to cross
      recognition of these two peptides by TCRs. Results presented in this
      communication are the first demonstration that a viral peptide with homology at
      just 5 amino acids with a self peptide can induce clinical signs of EAE in mice.
      These findings have important implications in understanding the breakdown of T
      cell tolerance to self Ags in autoimmune diseases by means of cross-reactivity
      with unrelated peptides.

PMID- 9647208
TI  - Pentoxifylline inhibits adhesion and activation of human T lymphocytes.
AB  - We have herein studied the effect of pentoxifylline (PTX) on the adhesion and
      activation of human T lymphocytes. We found that PTX inhibited the adhesion of T
      cells to the beta1 and beta2 integrin ligands VCAM-1 and ICAM-1; this inhibitory
      activity was dose dependent, with a maximal effect from 12 to 24 h. We also found
      that PTX was able to interfere with the activation of beta1 integrins induced by
      intracellular signals; however, the conformational change of beta1 integrins
      induced by extracellular stimuli (e.g., activating mAbs, or Mn2+) was not
      significantly affected by this drug. In addition, the homotypic aggregation of T
      cells induced by anti-beta1 and -beta2 integrin chain mAbs was also inhibited by
      PTX. PTX had a significant inhibitory effect on the T lymphocyte expression of
      the activation Ags CD25 (IL-2R alpha-chain), CD69 (activation-inducer molecule),
      and CD98 (4F2) induced by PHA. Accordingly, PTX also interfered with early cell
      activation events such as the rise in intracellular Ca2+ and the activation of
      the Na+/H+ antiporter induced by PHA and phorbol esters, respectively.
      Furthermore, this drug inhibited both the cell cycle progression and cell
      proliferation of T cells induced through the CD3/TCR complex. However, this drug
      did not show any effect on the cell activation/proliferation induced by PMA plus
      ionomycin. Our results indicate that PTX interferes efficiently with the
      activation and cell adhesion of human T lymphocytes. These effects may be of
      relevance for the clinical uses of this drug.

PMID- 9647209
TI  - De novo-developed T cells have compromised response to existing alloantigens:
      using Ld-specific transgenic 2C T cells as tracers in a mouse heart
      transplantation model.
AB  - In this study, the phenotype, TCR signaling events, and function of T cells
      developed de novo during adulthood in the presence of extrathymic alloantigen
      were investigated. C57BL/6 mice(H-2b) were first transplanted heterotopically
      with BALB/c hearts (H-2d) and treated with rapamycin for 2 wk to create a
      tolerant status. Three weeks postoperation, the mice were whole body irradiated
      and transplanted with bone marrow cells from 2C mice, which are transgenic for
      TCR, and most of their T cells are Ld-specific CD8 cells. The 2C T cells
      developed de novo in the C57BL/6 mice were not able to reject the heart
      allograft. No clonal deletion, TCR down-regulation, or CD8 down-regulation was
      found in the tolerized 2C T cells. There was no characteristic phenotype of these
      cells in terms of CD25, ICAM-1, CD44, and MEL-14 expression. Early TCR signaling
      events such as intracellular calcium concentration flux, tyrosine
      phosphorylation, Lck and Fyn kinase activities, and Lck and Fyn protein levels in
      the tolerized 2C T cells were comparable to their normal counterparts, but the
      tolerized T cells were defective in IL-2 production and proliferation upon H-2d
      alloantigen stimulation in vitro. Exogenous IL-2 could not reverse the
      compromised proliferation. The results of this study indicate that during
      adulthood, the de novo-developed T cells become tolerant to extrathymic Ag
      without clonal deletion. These newly minted T cells are functionally defective
      although they are indistinguishable from normal T cells in phenotypes and in some
      early signaling events.

PMID- 9647210
TI  - Allelic differences in the relationship between proteasome activity and MHC class
      I peptide loading.
AB  - MHC class I molecules are cell surface glycoproteins that play a pivotal role in
      the response to intracellular pathogens. The loading of MHC class I molecules
      with antigenic substrates takes place in the endoplasmic reticulum. This requires
      a functional TAP transporter, which translocates peptides into the endoplasmic
      reticulum from the cytosol. The generation of antigenic peptides from polypeptide
      precursors is thought to be mediated in the cytosol by the proteasome.
      Previously, we have demonstrated that inhibiting the proteasome with the specific
      covalent inhibitor lactacystin results in a direct reduction of peptide-loaded
      MHC class I molecules. This indicates that the proteasome is the limiting step in
      the MHC class I pathway. In this study we use isoelectric focusing to demonstrate
      that two related MHC class I alleles, HLA-A3 and HLA-A11, as well as HLA-B35 do
      not follow this behavior. In contrast to other class I alleles expressed by the
      same cells, these alleles are loaded with peptides and mature normally when
      proteasome activity is severely inhibited. Our observations highlight a new level
      of diversity in the MHC class I system and indicate that there are allele
      specific differences in the linkage between proteasome activity and MHC class I
      peptide loading.

PMID- 9647211
TI  - H2-M3 presents a nonformylated viral epitope to CTLs generated in vitro.
AB  - Most CTL responses to epitopes from influenza virus are restricted by MHC class
      Ia molecules. However, a synthetic peptide corresponding to residues 173 to 190
      of influenza A/JAP/305/57 hemagglutinin (HA) can induce, in vitro, a CTL response
      to peptide presented by a mouse class Ib molecule encoded by a gene telomeric to
      H2-Q. Here, we identify the molecule as H2-M3 and show that the last five
      residues of HA173-190, MLIIW, is the minimal epitope for CTL recognition. Cells
      that express M3wt, from C57BL/6 or BALB/c mice, are sensitized by both MLIIW and
      the longer peptide HA173-190, whereas cells that express M3f, from A.CA or B10.M
      mice, are sensitized only by MLIIW; a single amino acid change at residue 31 (V-
      >M) of M3 accounts for this difference. Although M3-restricted CTLs preferably
      recognize N-formylated epitopes, i.e., those of mitochondrial or prokaryotic
      origin, our findings show that M3-restricted primary CTL responses can be
      generated in vitro against nonformylated epitopes.

PMID- 9647212
TI  - In vivo persistence of CD8 polarized T cell subsets producing type 1 or type 2
      cytokines.
AB  - Naive CD8 T cells can be polarized into effectors producing the type 1 cytokines
      IFN-gamma and IL-2 or the type 2 cytokines IL-4, IL-5, and IL-10, respectively.
      To study whether the polarized cytokine phenotype of the effectors is stable, we
      generated highly cytotoxic hemagglutinin (HA) peptide-specific CD8 Tc1 and Tc2
      (cytotoxic CD8 T cells producing type 1 or type 2 cytokines) effectors from Clone
      4 TCR-transgenic mice, which were adoptively transferred into syngeneic adult
      thymectomized irradiated and bone marrow-reconstituted recipients. The highly
      activated blast-size, CD25+ Tc1 and Tc2 effectors gave rise to homogeneous
      resting CD25- CD44(high) Ly6C(high) Ag-specific populations, which persisted for
      at least 13 wk after adoptive transfer. These memory CD8 T cells, recovered 13 wk
      after transfer of Tc1 or Tc2 effectors, still produced either the type 1 or type
      2 cytokines, i.e., IFN-gamma, or IL-4 and IL-5, respectively, upon restimulation
      with APCs loaded with the HA peptide, but not in the absence of Ag. The amounts
      of IL-2 detected in the supernatants of Tc1 and Tc2 memory populations were
      comparable to that in memory CD4 cells, and both Tc1 and Tc2 memory cells became
      cytotoxic upon restimulation. Thus, cytokine-polarized CD8 memory T cells are a
      source of a variety of cytokines, which were classically considered helper
      cytokines, opening new perspectives on their function as regulatory cells in an
      immune response.

PMID- 9647213
TI  - TCR agonist and antagonist exert in vivo cross-regulation when presented on Igs.
AB  - Ig-PLP1 and Ig-PLP-LR are chimeric Igs expressing proteolipid protein (PLP)
      derived T cell agonist (PLP1) and antagonist (PLP-LR) peptides, respectively.
      Both chimeras, like free PLP1 and PLP-LR peptides, induce in vivo-specific T cell
      responses. However, the responses induced by Ig-PLP1 and Ig-PLP-LR were cross
      reactive with both PLP1 and PLP-LR peptides, while those induced by free peptides
      were not. Surprisingly, despite the cross-reactivity of the responses, when Ig
      PLP1 and Ig-PLP-LR were administered together into mice, a dose-dependent down
      regulation of both T cell responses and a reduction of IL-2 production to
      background levels was observed. In contrast, when T cells induced by either Ig
      chimera were stimulated in vitro with mixtures of free PLP1 and PLP-LR peptides,
      there was no down-regulation of proliferation or decrease in IL-2 production.
      These data indicate that Ig-PLP1 and Ig-PLP-LR exert adverse reactions on one
      another at the level of naive T cells, resulting in an opposite antagonism.
      However, naive T cells experiencing either chimera develop into cross-reactive
      cells, acquire resistance to TCR triggering by closely related but different
      peptides, and support responsiveness.

PMID- 9647214
TI  - Proteasomes can either generate or destroy MHC class I epitopes: evidence for
      nonproteasomal epitope generation in the cytosol.
AB  - Proteasomes have been implicated in the production of the majority of peptides
      that associate with MHC class I molecules. We used two different proteasome
      inhibitors, the peptide aldehyde N-acetyl-L-leucyl-L-leucyl-L-norleucinal (LLnL)
      and the highly specific inhibitor lactacystin, to examine the role of proteasomes
      in generating peptide epitopes associated with HLA-A*0201. Neither LLnL nor
      lactacystin was able to completely block the expression of the HLA-A*0201.
      Furthermore, the effects of LLnL and lactacystin on the expression of different
      categories of specific epitopes, TAP independent vs TAP dependent and derived
      from either cytosolic or membrane proteins, were assessed. As predicted,
      presentation of two TAP-dependent epitopes was blocked by LLnL and lactacystin,
      while a TAP-independent epitope that is processed in the endoplasmic reticulum
      was unaffected by either inhibitor. Surprisingly, both LLnL and lactacystin
      increased rather than inhibited the expression of a cytosolically transcribed and
      TAP-dependent peptide from the influenza A virus M1 protein. Mass spectrometric
      analyses of in vitro proteasome digests of a synthetic 24 mer containing this
      epitope revealed no digestion products of any length that included the intact
      epitope. Instead, the major species resulted from cleavage sites within the
      epitope. Although cleavage at these sites was inhibitable by LLnL and
      lactacystin, epitope-containing species were still not produced. We conclude that
      proteasomes may in some cases actually destroy epitopes that would otherwise be
      destined for presentation by class I molecules. These results suggest that some
      epitopes are generated by nonproteasomal proteases in the cytosol.

PMID- 9647215
TI  - Endogenous IL-12 is required for induction and expression of experimental
      autoimmune uveitis.
AB  - Experimental autoimmune uveitis (EAU) has been associated with a Th1 response.
      However, in IFN-gamma-deficient mice, EAU develops in the context of an effector
      response having Th2-like elements, and administration of IL-12 to mice immunized
      for EAU induction can be protective. We, therefore, investigated whether
      endogenous IL-12 is required for development of EAU. IL-12 p40-deficient mice
      (12KO) were resistant to EAU induced with the uveitogenic retinal Ag
      interphotoreceptor retinoid binding protein (IRBP). Delayed hypersensitivity to
      IRBP was marginally reduced, whereas Ag-specific proliferation was enhanced.
      Primed lymphocytes of wild-type (wt) mice, cultured with IRBP, produced a Th1
      like cytokine profile and transferred EAU to syngeneic wt recipients.
      Interestingly, the same cells were inefficient in transferring EAU to 12KO
      recipients, unless IL-12 was included in the culture. Primed cells of the 12KO
      mice produced a Th2-like cytokine profile and failed to transfer EAU. However,
      when IL-12 was added to the culture, 12KO cells produced large amounts of IFN
      gamma and transferred EAU to naive 12KO recipients. We conclude that resistance
      to EAU of 12KO mice is not due to an inherent inability of these mice to develop
      ocular disease. Despite an apparent similarity in Ag-specific cytokine responses
      to IFN-gamma-deficient mice, 12KO mice have inhibited generation of uveitogenic
      effector cells, a situation that can be reversed even after priming, by adding
      exogenous IL-12 ex vivo. Lastly, the diminished ability of primed wt lymphocytes
      to induce EAU in 12KO mice indicates a role for endogenous IL-12 in the efferent
      phase of disease expression that is distinct from its role during Ag priming.

PMID- 9647216
TI  - In vivo expression of a TCR antagonist: T cells escape central tolerance but are
      antagonized in the periphery.
AB  - Transgenic 3.L2 T cells are stimulated by Hb(64-76)/I-Ek and are positively
      selected on I-Ek plus self-peptides. To this pool of self-peptides we have added
      a single, well-defined 3.L2 TCR antagonist (A72) in vivo. We find that mice
      expressing both the 3.L2 TCR and A72 have a minimal loss of T cells expressing
      the clonotypic TCR in the thymus and spleen. Importantly, the proliferative
      response of 3.L2 x A72 splenocytes is significantly reduced compared with
      splenocytes from 3.L2 mice. This reduced response can be attributed to peripheral
      antagonism. Thus we have identified a new class of self-ligands whose predominant
      effect is constitutive peripheral antagonism rather than negative selection. The
      net effect of these ligands is to avoid potential self-reactivity while
      maintaining as large a repertoire as possible.

PMID- 9647217
TI  - Characterization of human fibroleukin, a fibrinogen-like protein secreted by T
      lymphocytes.
AB  - We have recently cloned the human homologue of the murine pT49 cDNA (hpT49h), a
      transcript encoding a protein homologous to the beta- and gamma-chains of
      fibrinogen. Here, we report the identification of the hpT49h gene product using
      mAbs generated against a peptide corresponding to the carboxyl-terminal end of
      the deduced protein and a recombinant protein fragment expressed in Escherichia
      coli. mAbs 23A6, 7B12, and 3F4 specifically recognized a protein of 70 kDa in
      reducing SDS-PAGE in the culture supernatant of 293T cells transiently
      transfected with the full length hpT49h cDNA and freshly isolated PBMC. Under
      nonreducing conditions, the material migrated with a molecular mass of 250 to 300
      kDa, indicating that the 70-kDa protein forms a disulfide bonded complex. Because
      of its homology with fibrinogen, we have termed this protein fibroleukin.
      Fibroleukin is spontaneously secreted in vitro by freshly isolated CD4+ and CD8+
      T lymphocytes. RT-PCR analysis revealed preferential expression of fibroleukin
      mRNA in memory T lymphocytes (CD3+/CD45R0+) compared with naive T lymphocytes
      (CD3+/CD45RA+). Fibroleukin production by PBMC was rapidly lost in culture.
      Production could be partially maintained in the presence of IFN-gamma, while T
      lymphocyte activation had no effect. To demonstrate fibroleukin production in
      vivo, we analyzed colon mucosa by immunohistology. Fibroleukin staining was
      detected in the extracellular matrix of the T lymphocyte-rich upper portion of
      the lamina propria mucosa. While the exact function of fibroleukin remains to be
      defined, these data suggest that fibroleukin may play a role in physiologic
      lymphocyte functions at mucosal sites.

PMID- 9647218
TI  - Strong alloantigenicity of the alpha-helices residues of the MHC class I
      molecule.
AB  - To evaluate the role of single residues of a MHC class I molecule in the
      induction of a primary allogeneic response, we have tested the ability of various
      point mutants (of the alpha-helices or beta-sheet of the alpha1 and alpha2
      domains) of the Kd molecule to induce a primary cytotoxic T cell response in mice
      carrying the wild-type molecule. For that, we have used an in vivo model in which
      cells expressing mutant molecules were injected into the hind footpads of mice
      carrying wild-type Kd, and the recipient graft-draining popliteal lymph nodes
      were tested for the presence of alloreactive CTL. Under these experimental
      conditions, only 7 of the 25 mutant Kd molecules induced a primary allogeneic
      response. All of these mutations (positions 62, 65, 69, 72, 155, 163, 166)
      concern residues of the alpha-helices, demonstrating that very small variances
      from self in a class I molecule, located outside the peptide-binding groove, can
      be antigenic. To determine the peptide requirements for the generation of a
      primary allogeneic response, we have analyzed the repertoire of peptides selected
      by individual mutant molecules shown to be able or unable to induce a CTL
      response. No correlation was observed between the peptidic make-up presented by a
      given mutant and its capacity to induce a primary allogeneic response. On the
      whole, our data point to the alloantigenicity of potentially TCR-contacting
      surface residues of the MHC class I molecules.

PMID- 9647219
TI  - Induction of oral tolerance in TGF-beta 1 null mice.
AB  - Previous studies have suggested that oral tolerance induction by low doses of Ag
      is mediated by inhibitory cytokines, particularly TGF-beta 1. To examine the
      roles of TGF-beta 1 and other inhibitory cytokines in the induction of oral
      tolerance, TGF-beta 1 null mice and controls were gavaged with 10 to 20 mg (high
      dose) or 1 mg (low dose) of OVA for 3 days. After immunization with OVA, the in
      vitro proliferative response of OVA-specific popliteal lymph node cells was
      assessed. Lymphocytes from all TGF-beta 1 null mice fed high doses of OVA
      exhibited highly significant suppression compared with controls. A weaker, but
      still significant, suppression was observed in lymphocytes from the majority of
      TGF-beta 1 null mice fed low doses of OVA. In addition, supernatants from these
      lymphocytes exhibited lower levels of IL-4, IL-10, and IFN-gamma than those from
      water-fed control animals. These results indicate that while TGF-beta 1 may play
      a role in suppression, inhibitory cytokines are not the exclusive mechanism by
      which low dose oral tolerance is induced.

PMID- 9647220
TI  - A role for heat shock protein 27 in CTL-mediated cell death.
AB  - CTL exocytosis of granules containing perforin and granzyme proteases induces
      apoptotic cell death. Either granzyme A or B can act with perforin to trigger
      apoptosis. Granzyme B activates a ubiquitous apoptotic cascade induced by caspase
      cleavage, but the granzyme A pathway is largely unknown. Using affinity
      chromatography with recombinant mutant inactive granzyme A, we previously
      isolated two granzyme A-binding proteins, PHAP (putative HLA-associated protein)
      I and II. PHAP II, a substrate of granzyme A, is degraded within minutes of CTL
      attack. Two additional cytoplasmic proteins of 27 and 53 kDa bind strongly to the
      mutant granzyme A column, requiring 6 M urea to elute. Sequencing identified
      these as the monomer and dimer of hsp27, a small heat shock protein up-regulated
      by stress and cellular activation. Hsp27 coprecipitates with granzyme A from
      cytoplasmic lysates and is not a substrate of the enzyme. Hsp27 translocates to
      the detergent-insoluble fraction of target cells and relocalizes from diffuse
      cytoplasmic staining to long filamentous fibers, especially concentrated in a
      perinuclear region, within minutes of CTL attack. Hsp27 may participate in
      morphologic changes during granule-mediated lysis. Low or absent levels of hsp27
      expression in T lymphocytes, even after heat shock, may play a role in CTL
      resistance to granule-mediated lysis.

PMID- 9647221
TI  - A comparison of signaling requirements for apoptosis of human B lymphocytes
      induced by the B cell receptor and CD95/Fas.
AB  - To define how the signaling pathways that mediate the B cell receptor (BCR) death
      pathway differ from those responsible for CD95/Fas-mediated death, we compared
      the BCR and Fas death pathways in two human B cell lines, B104 and BJAB. Both BCR
      and Fas-induced apoptosis are blocked by the peptide cysteine protease inhibitor
      benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (ZVAD (mlz)), demonstrating a
      common requirement caspase activity. Despite this common characteristic, the
      ability of actinomycin D and cycloheximide to block BCR-induced apoptosis, but
      not apoptosis induced by Fas cross-linking, suggests that a major difference
      between these two pathways is their differential requirements for new gene and
      protein synthesis. BCR- and Fas-mediated apoptosis are both accompanied by
      activation of stress-activated protein kinase and p38 mitogen-activated protein
      kinase (MAPK). Activation of both stress-activated protein kinase and p38 MAPK
      was inhibited by ZVAD (mlz), suggesting the involvement of caspases. To determine
      the role of p38 MAPK activation in BCR- and Fas-induced apoptosis, we employed
      SB203580, a specific inhibitor of p38 MAPK. SB203580 inhibited BCR-induced
      apoptosis, but not apoptosis induced by cross-linking Fas. Furthermore, both
      actinomycin D and SB203580 inhibited BCR-induced, but not Fas-induced, activation
      of caspase. Collectively, these findings establish a role for p38 MAPK in BCR
      induced apoptosis both upstream and downstream of caspase activity. The p38 MAPK
      pathway may function to regulate transcriptional or translational events that are
      critical for BCR-induced apoptosis.

PMID- 9647222
TI  - CD4+ T cells mature in the absence of MHC class I and class II expression in Ly
      6A.2 transgenic mice.
AB  - The TCRs expressed on T lymphocytes recognize foreign peptides bound to MHC
      molecules. This reactivity is the basis of specific immune response to the
      foreign Ag. How such specificities are generated in the thymus is still being
      debated. Signals generated through TCR upon interaction with self MHC-peptide
      complexes are critical for maturation of the CD4+ helper and CD8+ cytotoxic
      subsets. We have observed maturation of CD4+ but not CD8+ T cells in Ly-6A.2
      transgenic MHC null mice. Since there can be no interactions with MHC molecules
      in these mice, these CD4+ cells must express the T cell repertoire that exists
      before positive and negative selection. Interestingly, despite an absence of
      selection by MHC molecules, the CD4+ cells that mature recognize MHC molecules at
      a frequency as high as in CD4+ cells in normal mice. These results demonstrate
      that: 1) the germline sequences encoding TCRs are biased toward reactivity to MHC
      molecules; and 2) CD4+ cells as opposed to CD8+ cells have distinct lineage
      commitment signals. These results also suggest that signals originating from Ly-6
      can promote or substitute for signals generated from TCR that are required for
      positive selection. Moreover, this animal model offers a system to study T cell
      development in the thymus that can provide insights into mechanisms of lineage
      commitment in developing T cells.

PMID- 9647223
TI  - The cytoplasmic domain of CD8 beta regulates Lck kinase activation and CD8 T cell
      development.
AB  - Previous studies have shown that CD8 beta plays a role in both enhancing CD8
      alpha-associated Lck kinase activity and promoting the development of CD8-lineage
      T cells. To examine the role of this enhancement in the maturation of CD8-lineage
      cells, we assessed CD8 alpha-associated Lck kinase activity in both T cell
      hybridomas and thymocytes of mice expressing CD8 beta mutations known to impair
      CD8 T cell development. Lack of CD8 beta expression or expression of a
      cytoplasmic domain-deleted CD8 beta resulted in a severalfold reduction in CD8
      alpha-associated Lck kinase activity compared with that observed with cells
      expressing wild-type CD8 beta chain. This analysis indicated a critical role for
      the cytoplasmic domain of CD8 beta in the regulation of CD8 alpha-associated Lck
      activity. Decreased CD8 alpha-associated Lck activity observed with the various
      CD8 beta mutations also correlated with diminished in vivo cellular tyrosine
      phosphorylation. In addition, analysis of CD8 beta mutant mice (CD8 beta-/- or
      cytoplasmic domain-deleted CD8 beta transgenic) indicated that the degree of
      reduction in CD8 alpha-associated Lck activity associated with each mutation
      correlated with the severity of developmental impairment. These results support
      the importance of CD8 beta-mediated enhancement of CD8 alpha-associated Lck
      kinase activity in the differentiation of CD8 single-positive thymocytes.

PMID- 9647224
TI  - Tissue-specific up-regulation of B7-1 expression and function during the course
      of murine relapsing experimental autoimmune encephalomyelitis.
AB  - B7/CD28-mediated costimulation is a promising target for therapeutic intervention
      in autoimmune diseases. However, studies addressing the differential functional
      roles of B7-1 and B7-2 in several autoimmune models have resulted in conflicting
      data, perhaps due to the temporal dynamics of B7-1 and B7-2 surface expression on
      different cell types and/or at different sites during an autoimmune response. We
      examined the temporal expression of B7 costimulatory molecules in the CNS and in
      various lymphoid organs during the course of murine relapsing-remitting
      experimental autoimmune encephalomyelitis (R-EAE). Following immunization of SJL
      mice with the immunodominant proteolipid protein epitope, PLP139-151, surface
      expression of B7-1 was up-regulated on B cells, T cells, and macrophages,
      relative to B7-2, on CNS-infiltrating cells and on splenocytes. Similar
      enhancement in splenic B7-1 expression could be induced in SJL mice by the
      adoptive transfer of PLP139-151-specific cells or by immunization with CFA alone.
      These changes were not observed on lymph node cells, including those isolated
      from lymph nodes draining the immunization site, which maintained the predominant
      B7-2 expression pattern seen in naive mice. These phenotypic expression patterns
      correlated with the functional predominance of B7-1 in costimulating T cell
      activation when employing APCs from the spleen or CNS of mice with ongoing R-EAE,
      while B7-2 remained functionally predominant on lymph node APCs. Variation of
      phenotypic expression and functional dominance of costimulatory molecule
      expression in different lymphoid compartments during an active inflammatory
      autoimmune response has important implications in immune regulation, autoimmune
      pathogenesis, and therapeutic strategies.

PMID- 9647225
TI  - A partially modified retro-inverso pseudopeptide modulates the cytokine profile
      of CTL specific for an influenza virus epitope.
AB  - There is considerable evidence that peptides corresponding to MHC class I
      restricted epitopes can be used as immunogens or immunomodulators. Pseudopeptides
      containing isosteric replacements of the amide bond provide more stable
      analogues, which may even have enhanced biologic activity. But there have been
      very few studies on the use of pseudopeptides to initiate or modulate the
      cellular immune response. This study describes the immunogenicity of a partially
      modified retro-inverso pseudopeptide of an influenza virus epitope and shows that
      this pseudopeptide modulates the cytokine profile expressed by CD8+ CTL generated
      from primed precursors. Moreover, the pseudopeptide is much more efficient at low
      concentration than the wild-type epitope to stimulate IFN-gamma secretion by CD8+
      T effector cells. These results are analyzed with reference to changes in the
      conformation of the MHC molecule/peptide complex deduced from molecular modeling.
      The findings support the idea that partially modified retro-inverso analogues can
      be used as altered peptide ligands to enhance the stimulation of natural epitope
      specific CTL and to modify their functional properties. Hence, pseudopeptide
      ligands might be promising tools for use in immunotherapy.

PMID- 9647226
TI  - V7 (CD101) ligation inhibits TCR/CD3-induced IL-2 production by blocking Ca2+
      flux and nuclear factor of activated T cell nuclear translocation.
AB  - Ligation of the V7 (CD101) molecule on T cells with anti-V7 mAb blocks TCR/CD3
      induced proliferation by inhibiting IL-2 transcription. To explore the basis for
      this observation, we analyzed the effects of V7 ligation on CD3/TCR-induced
      changes in intracellular free Ca2+ and Ca2+-dependent nuclear factor of activated
      T cells (NF-AT) translocation to the nucleus, which is required for IL-2
      transcription. T cells exposed to anti-V7 mAb fluxed Ca2+ transiently, but did
      not flux Ca2+ in response to subsequent treatment with anti-CD3; however, they
      recovered the capacity to flux Ca2+ after treatment with pervanadate, indicating
      that tyrosine dephosphorylation of a critical V7-related substrate is required in
      the desensitization process. One such substrate, phospholipase C (PLC)-gamma1,
      becomes tyrosine phosphorylated on CD3/TCR activation and mediates inositol
      triphosphate-dependent Ca2+ flux. Co-cross-linking of T cells with anti-CD3 and
      anti-V7 resulted in selective inhibition of PLC-gamma1 tyrosine phosphorylation,
      which may explain V7-mediated blockade of anti-CD3-induced Ca2+ flux. Moreover,
      anti-CD3-induced binding of transcription factors to a consensus NF-AT-binding
      oligonucleotide, which is dependent on Ca2+, was blocked completely by treatment
      of the cells with anti-V7, whereas binding to a consensus-activating protein-1
      oligonucleotide was unaffected. Western blot analysis of cytoplasmic and nuclear
      extracts confirmed that anti-V7 prevented nuclear translocation of NF-ATc induced
      by anti-CD3. We conclude that V7 ligation interferes with T cell activation and
      IL-2 secretion through a Ca2+ and tyrosine kinase-dependent pathway that inhibits
      PLC-gamma1 phosphorylation and prevents NF-AT translocation to the nucleus.

PMID- 9647227
TI  - Differential regulation of the Janus kinase-STAT pathway and biologic function of
      IL-13 in primary human NK and T cells: a comparative study with IL-4.
AB  - IL-13, a cytokine similar to IL-4, is a regulator of human B cell and monocyte
      functions. Biologic effects of IL-13 on primary human NK and T cells have not
      been well defined. We demonstrate that, in primary NK cells, IL-13, but not IL-4,
      may induce low levels of IFN-gamma secretion. When NK cells were costimulated
      with IL-13 and IL-2, IL-13 generally resulted in two types of reactivity: IL-13
      synergized with IL-2 to stimulate IFN-gamma production or it modestly inhibited
      IL-2-mediated IFN-gamma production. In both types of donors, the effect of IL-13
      on IL-2-induced IFN-gamma production was in marked contrast to the strong
      inhibition seen with IL-4 in NK cells. Additionally, IL-13 suppresses IL-2
      induced NK cytolytic and proliferative activities although less efficiently than
      IL-4. In T cells, IL-13 inhibits anti-CD3 mAb/IL-2- or PHA-mediated IFN-gamma
      production and enhances cytolytic potential. Furthermore, we demonstrate that IL
      13, like IL-4, induces distinct STAT6-DNA binding complexes and tyrosine
      phosphorylation of STAT6 and Janus kinase 3 (JAK3) in NK and T cells. We observed
      that Abs directed against unique domains of STAT6 have differential effects on
      complexes in T cells but not in NK cells, suggesting different STAT6 isoforms.
      These findings show that IL-13 and IL-4 have the ability to regulate NK and T
      cell activation and that IL-13 is a potent regulator of STAT6 and JAK3 in these
      cell types.

PMID- 9647228
TI  - Development of human peripheral TCRBJ gene repertoire.
AB  - Previous studies of TCRBJ gene repertoires of human peripheral T lymphocytes
      showed that all TCRBV family transcripts had some common features in BJ gene
      usage, and nevertheless, transcripts of each BV family gene had a distinct
      pattern. To discern how the development of the peripheral BJ repertoire is
      controlled, the effects of preferential BJ gene rearrangement, thymic selection,
      and peripheral stimulation on the repertoire formation were investigated. A PCR
      ELISA technique was used to examine the immature CD3- CD4+ CD8-, and mature CD3+
      CD4+ CD8- and CD3+ CD4- CD8+ thymocytes, and peripheral CD4+ and CD8+ T
      lymphocytes for their BJ gene repertoires. Analogous to the peripheral
      repertoire, the BJ gene repertoires of the immature thymocytes displayed common
      features, and each BV transcript had a distinct pattern. All features were
      conserved well by those of mature thymocytes and peripheral T lymphocytes. In
      addition, the BJ gene repertoires of mature CD4 and CD8 thymocytes and peripheral
      lymphocytes with the same coreceptors were apparently different in a few BV-BJ
      combinations. The results showed that the overall BJ gene repertoire pattern was
      developed before antigenic selection. Thus, the preferential BJ gene expression,
      primarily based on preferential use of certain BJ gene rearrangements, dictates
      the peripheral BJ gene repertoire, which is then further modified by thymic
      selection and peripheral stimulation.

PMID- 9647229
TI  - The prototypic Th2 autoimmunity induced by mercury is dependent on IFN-gamma and
      not Th1/Th2 imbalance.
AB  - Imbalances of Th1- and Th2-type responses have been postulated to be a
      predisposing factor for both humoral and cellular mediated autoimmune diseases.
      To further define their roles in systemic autoimmunity, IL-4 and IFN-gamma gene
      knockout mice were studied for susceptibility to the prototypic Th2-mediated
      mercury-induced autoimmunity. A predominant Th2-type response following HgCl2
      treatment of wild-type B10.S mice was confirmed by the findings of a significant
      increase in splenic IL-4 and hypergammaglobulinemia primarily of the IgG1
      isotype, without an increase in IFN-gamma levels. Paradoxically, IL-4-deficient
      mice developed the characteristic anti-nucleolar autoantibodies and tissue
      deposition of immune complexes, while IFN-gamma-deficient mice had very low
      autoantibody levels and essentially normal immunohistology. Studies to define
      defects in Ab responses of IFN-gamma-deficient mice, using the T-dependent Ag (4
      hydroxy-3-nitrophenyl)acetyl, revealed an attenuated IgG response to low and to a
      lesser extent high doses of (4-hydroxy-3-nitrophenyl)acetyl-hemocyanin, but
      maintenance of affinity maturation. These results indicate that Th1/Th2 imbalance
      does not directly play a role in susceptibility to mercury-induced autoimmunity,
      and suggest that the dependence on Th1-type responses in certain autoimmune
      diseases is due to the requirement for IFN-gamma for Ab production to weakly
      antigenic self molecules.

PMID- 9647230
TI  - Fas/Fas ligand interactions are involved in ultraviolet-B-induced human
      lymphocyte apoptosis.
AB  - We wondered whether the apoptosis known to occur after UV-B irradiation might
      involve the Fas/Fas ligand (FasL) signaling pathway. We exposed PBLs from normal
      individuals, and also the Jurkat (E6-1) and U937 cell lines, to graded doses of
      UV-B irradiation and observed a prompt and marked increase in Fas expression at
      doses as low as 0.5 mJ/cm2. Increased Fas expression did not require new protein
      synthesis, since cycloheximide-treated cells also showed an increase in Fas after
      UV-B. UV-B-irradiated cells cultured in the presence of zinc showed inhibition of
      apoptosis coincident with a marked increase in Fas+ cells, apparently indicating
      the accumulation of Fas-bearing cells unable to undergo apoptosis. After UV-B
      irradiation, PBLs showed increased expression of Fas ligand; the E6-1 lymphocytic
      cell line also released soluble FasL. UV-B induced apoptosis could be partially
      blocked by neutralizing FasL Abs, and a FasL-resistant variant of E6-1 cell line
      showed reduced apoptosis after UV-B irradiation, implying that the increase in
      Fas expression signified a role for Fas in UV-induced apoptosis. UV-induced Fas
      expression may serve to target stress-injured cells for removal by FasL-bearing
      cells or by FasL produced by the cells themselves in response to the stimuli, and
      may represent a general function of the Fas/FasL pathway in facilitating the
      apoptosis and elimination of undesirable or harmful cells.

PMID- 9647231
TI  - Role of mu heavy chain in B cell development. I. Blocked B cell maturation but
      complete allelic exclusion in the absence of Ig alpha/beta.
AB  - There is good evidence for a signaling role played by Ig heavy chain in the
      developmental transition through the pre-B cell stage. We have previously
      described signal-capable or signal-incapable mutants of mu heavy chain in which a
      signaling defect is caused by failure to associate with the Ig alpha/beta
      heterodimer. To further characterize the role of Ig heavy chain-mediated
      signaling in vivo, as well as in B cell development and allelic exclusion, we
      have created transgenic mice in which the B cells express these signal-capable
      and signal-incapable mutant mu chains. Failure of mu to signal via Ig alpha/beta
      results in a block in B cell development in mice expressing the signal-incapable
      mu. A small number of B cells in these animals do escape the developmental block
      and are expressed in the spleen and the periphery as B220+ transgenic IgM+ cells.
      These cells respond to LPS by proliferating but show no response to T-independent
      specific Ag. In contrast, B cells expressing the signal-capable B cell receptor
      show a strong signaling response to Ag-specific stimulus. There is no Ig alpha
      seen in association with signal-deficient IgM. Thus, the B cell receptor complex
      is not assembled, and no signal can be delivered. Despite the block in
      developmental signaling, allelic exclusion is complete. There is no detectable
      coexpression of transgenic IgM and endogenous murine IgM, nor is there
      rearrangement of the endogenous heavy chain genes. This suggests that differing
      signaling mechanisms are responsible for the developmental transition and allelic
      exclusion and thus allows for separate examination of these signaling mechanisms.

PMID- 9647232
TI  - Two distinct pathways exist for down-regulation of the TCR.
AB  - TCR down-regulation plays an important role in modulating T cell responses both
      during T cell development and in mature T cells. Down-regulation of the TCR is
      induced by engagement of the TCR by specific ligands and/or by activation of
      protein kinase C (PKC). We report here that ligand- and PKC-induced TCR down
      regulation is mediated by two distinct, independent mechanisms. Ligand-induced
      TCR down-regulation is dependent on the protein tyrosine kinases p56(lck) and
      p59(fyn) but independent of PKC and the CD3gamma leucine-based (L-based)
      internalization motif. In contrast, PKC-induced TCR down-regulation is dependent
      on the CD3gamma L-based internalization motif but independent of p56(lck) and
      p59(fyn). Finally, our data indicate that in the absence of TCR ligation, TCR
      expression levels can be finely regulated via the CD3gamma L-based motif by the
      balance between PKC and serine/threonine protein phosphatase activities. Such a
      TCR ligation-independent regulation of TCR expression levels could probably be
      important in determining the activation threshold of T cells in their encounter
      with APC.

PMID- 9647233
TI  - Both PU.1 and nuclear factor-kappa B mediate lipopolysaccharide- induced HIV-1
      long terminal repeat transcription in macrophages.
AB  - We recently reported that LPS stimulation of monocytic cells leads to the
      activation of PU.1, a member of the Ets family of transcription factors.
      Phosphorylation of PU.1 by protein kinase CK2 was found to up-regulate its trans
      activation function, but not its DNA binding activity. Previous studies suggested
      that Ets proteins could bind to NF-kappa B motifs at the tetrameric core sequence
      TTCC. In macrophages, LPS-inducible HIV-1 gene expression is mediated in part by
      binding of NF-kappa B to identical tandem binding sites located within the long
      terminal repeat (LTR). Thus, we performed additional studies to determine whether
      PU.1 also played a role in regulating HIV-1 gene expression in macrophages. Our
      functional studies revealed that activation of the HIV-1 LTR in LPS-stimulated
      cells requires both NF-kappa B and PU.1. Extensive mutagenesis of the HIV-1 LTR
      revealed that PU.1-dependent activation requires the Ets motif within the
      upstream NF-kappa B site, whereas NF-kappa B itself binds to the downstream site.
      We also found that insertion of five additional nucleotides between the NF-kappa
      B sites abolished LPS inducibility, suggesting a direct interaction between
      factors that bind these sites. Lastly, we found that mutation of PU.1 at serine
      148, which prevents its phosphorylation by CK2, blocked its ability to activate
      the HIV-1 LTR in response to LPS. These effects were promoter specific because
      PU.1 did not affect LPS-inducible activation of a distinct NF-kappa B-dependent
      promoter. While these data do not demonstrate direct binding of PU.1 to the HIV-1
      LTR, they illustrate a novel role for PU.1 in activation of the HIV-1 LTR by LPS.

PMID- 9647234
TI  - An NFAT-dependent enhancer is necessary for anti-IgM-mediated induction of murine
      CD5 expression in primary splenic B cells.
AB  - CD5 is a 67-kDa membrane glycoprotein the expression of which in murine splenic B
      cells is induced by surface IgM cross-linking. To analyze this induction, we
      transiently transfected primary splenic B cells with luciferase reporter
      constructs driven by various wild-type and mutated CD5 5'-flanking sequences. The
      transfected cells were subsequently cultured in medium with or without F(ab')2
      anti-IgM (anti-IgM), and luciferase expression was assayed. Using this approach,
      we identified a 122-bp enhancer element necessary for anti-IgM-mediated induction
      of the CD5 promoter. Electrophoretic mobility shift assays indicated that four
      inducible and four constitutive complexes form on the enhancer fragment in
      nuclear extracts of primary B cells. Supershift assays revealed that two of the
      inducible complexes contained NFATc. Point mutations that abolished NFAT binding
      severely impaired enhancer function. Thus, CD5 is a target of NFAT in B cells. A
      third inducible complex required an intact H4TF-1 site. One of several
      constitutive complexes required an intact Ebox site while a second required an
      intact putative ets binding site. Mutation of the H4TF-1, Ebox, and Ets sites, in
      the presence of wild-type NFAT sites, significantly reduced the activity of the
      enhancer. Therefore, the induction of B cell CD5 expression requires NFAT binding
      and binding to at least one of three additional sites in the CD5 enhancer.

PMID- 9647235
TI  - Crucial role of TCR gamma chain junctional region in prenyl pyrophosphate antigen
      recognition by gamma delta T cells.
AB  - Human gamma delta T cells recognize prenyl pyrophosphate Ags and their analogues
      in a V gamma 2V delta 2 TCR-dependent manner. Few data are available regarding
      the TCR structural requirements for recognition of such prenyl pyrophosphate Ags
      by gamma delta T cells. Presently, we made chain pair switch, chimeric, and site
      mutant gamma delta TCRs and transfected them into TCR- mutant Jurkat T cells to
      examine the effects of changing the TCR gamma junctional region sequences on
      reactivity to prenyl pyrophosphate Ags. Substitution of the TCR gamma junctional
      region (N and J) sequences from an Ag-reactive TCR with TCR gamma junctional
      region sequences from an Ag-nonreactive TCR abrogated reactivity to the prenyl
      pyrophosphate Ag isopentenyl pyrophosphate and to its synthetic analogue ethyl
      pyrophosphate but not to a mycobacterial supernatant containing a mixture of
      prenyl pyrophosphate Ags. Substitution of only the TCR gamma N nucleotide region
      with that from this Ag-nonreactive TCR destroyed reactivity to isopentenyl
      pyrophosphate and to the mycobacterial supernatant. Substitution of the entire V
      delta 2 chain from the Ag-reactive TCR with a V delta 1 chain from an Ag
      nonreactive TCR yielded a prenyl pyrophosphate Ag-nonreactive TCR. Thus, using
      TCR mutagenesis and TCR transfectants, we show that gamma delta TCR reactivity to
      prenyl pyrophosphate Ags is dependent upon the junctional region of the TCR gamma
      chain and upon pairing of V gamma 2 and V delta 2 TCR chains. These structural
      requirements of TCR gamma delta recognition of prenyl pyrophosphates distinguish
      this reactivity from that of protein superantigens and emphasize the importance
      of the TCR gamma CDR3 loop and adjacent residues.

PMID- 9647236
TI  - A lambda 3' enhancer drives active and untemplated somatic hypermutation of a
      lambda 1 transgene.
AB  - Somatic hypermutation is a highly regulated process that targets mutations to the
      rearranged Ig genes. Little is known about the cis-elements required for somatic
      hypermutation of the lambda light chain gene. We have studied somatic
      hypermutation of a rearranged lambda 1 transgene under the control of either a
      lambda 2-4 or kappa 3' enhancer. The mutations in the transgenes were analyzed by
      sequencing DNA amplified from hypermutating Peyer's patch B cells. The results
      indicate that the lambda 3' enhancer can drive active hypermutation of a lambda 1
      transgene in Peyer's patch cells. The lambda 1 transgene under analysis carried
      two marked V lambda 2 genes immediately upstream that could serve as sequence
      donors in possible gene conversion events. There was no evidence of sequence
      transfer to the hypermutated lambda 1 gene, suggesting that gene conversion is
      not a major mechanism for somatic hypermutation in mice.

PMID- 9647237
TI  - STAT6 is required for IL-4-induced germline Ig gene transcription and switch
      recombination.
AB  - Transcription of the germline C gamma1 and C epsilon Ig genes is believed to be a
      necessary prerequisite for isotype switching to IgG1 and IgE, respectively. IL-4
      stimulation and ligation of CD40 can each independently induce low level germline
      gamma1 and epsilon transcription in murine B cells. Together these signals act
      synergistically to promote high level germline transcription and are normally
      required for T-dependent isotype switching to IgG1 and IgE. The STAT6
      transcription factor has been suggested to play a critical role in IL-4-induced
      activation of germline C gamma1 and C epsilon genes. To directly assess the role
      of STAT6 in IL-4R- and CD40-mediated germline transcription and switching, we
      have analyzed these events in splenic B cells from STAT6-deficient mice. Our
      results demonstrate that IL-4 does not induce detectable levels of germline
      gamma1 or epsilon transcripts in STAT6-deficient B cells. Germline transcript
      expression induced by CD40 stimulation alone is unaffected, but synergism between
      CD40- and IL-4R-mediated signals is completely ablated. Switch recombination to S
      gamma1, as measured by digestion-circularization PCR, is dramatically reduced in
      STAT6-deficient B cells stimulated with CD40 ligand plus IL-4. Similarly,
      germline gamma1 transcript expression and switch recombination to S gamma1 are
      also impaired in STAT6-deficient B cells stimulated with IL-4, IL-5, and anti-IgD
      Abs conjugated to dextran, a model for T-independent type II responses. These
      results directly demonstrate a critical role for STAT6 in the IL-4-mediated
      activation of germline Ig gene transcription and switch recombination in
      nontransformed B cells.

PMID- 9647238
TI  - Expression and characterization of recombinant subunits of human complement
      component C8: further analysis of the function of C8 alpha and C8 gamma.
AB  - Human C8 is composed of three nonidentical subunits (C8 alpha, C8 beta, and C8
      gamma) that are encoded in separate genes. In C8 isolated from serum, these are
      arranged as a disulfide-linked C8 alpha-gamma dimer that is noncovalently
      associated with C8 beta. In this study, a recombinant form of C8 alpha-gamma was
      expressed independently of C8 beta in insect cells and COS-7 cells and was shown
      to be equivalent to serum-derived C8 alpha-gamma with respect to its ability to
      combine with C8 beta and form functional C8. Also expressed separately were
      mutant (mut) forms of C8 alpha and C8 gamma in which the single interchain
      disulfide bond was eliminated. MutC8 alpha exhibited the ability to combine with
      C8 beta and express hemolytic activity, although at a lower level than human C8.
      Addition of purified mutC8 gamma increased this activity, presumably by binding
      to mutC8 alpha. A possible role for C8 gamma as a retinol binding protein was
      also investigated. Absorbance spectroscopy and fluorescence emission and
      quenching revealed no specific binding of retinol to mutC8 gamma. Together, these
      results indicate that 1) the biosynthesis and secretion of C8 alpha-gamma is not
      dependent on C8 beta, which is consistent with in vivo observations in C8 beta
      deficient humans; 2) C8 alpha can be synthesized independently of C8 gamma;
      therefore, protection of C8 alpha from premature membrane interactions during
      biosynthetic processing is not a likely function of C8 gamma; 3) C8 gamma
      enhances but is not required for expression of C8 activity; and 4) C8 gamma does
      not bind retinol; therefore, it cannot function as a retinol transport protein.

PMID- 9647239
TI  - The N-terminal domains target TNF receptor-associated factor-2 to the nucleus and
      display transcriptional regulatory activity.
AB  - The subcellular localization of the TNF receptor-associated factor-2 (TRAF2)
      adaptor protein in human endothelial cells, which mediates proinflammatory
      responses of TNF, has been analyzed by confocal immunofluorescence microscopy and
      by Western blotting of fractionated cell extracts. Rabbit antisera reactive with
      either amino- or carboxyl-terminal TRAF2 peptides frequently but not uniformly
      stain nuclei of cultured HUVEC or the established human endothelial cell line,
      ECV304. However, Western blotting reveals significant heterogeneity in the
      reactivities of these polyclonal Abs. Transiently transfected HUVEC expressing
      FLAG epitope-tagged TRAF2 consistently show prominent nuclear localization, and
      deletion mutants of TRAF2 identify the portion of the molecule responsible for
      nuclear localization as the amino-terminal ring finger domain. TNF treatment does
      not appear to influence the localization of endogenous or transfected TRAF2
      protein. Transfection of the amino-terminal half of the TRAF2 molecule,
      containing the ring and zinc finger domains, which localizes to the nucleus,
      results in activation of E-selectin but not of NF-kappaB promoter-reporter gene
      transcription or of c-Jun N-terminal kinase activation. These observations
      suggest that TRAF2 may reside in the nucleus and directly regulate transcription,
      independent of its role in cytoplasmic signal transduction.

PMID- 9647240
TI  - Regulation of IL-6 signaling by p53: STAT3- and STAT5-masking in p53-Val135
      containing human hepatoma Hep3B cell lines.
AB  - The influence of p53 on cytokine-triggered Janus kinase-STAT signaling was
      investigated in human hepatoma Hep3B cell lines engineered to constitutively
      express the temperature-sensitive Val135 mutant of p53. In comparison to the
      parental p53-free Hep3B cells, these p53-Val135-containing Hep3B cell lines
      displayed a reduced response to IL-6 at the wild-type-like p53 temperature (32.5
      degrees C). In these cells, IL-6 induced a marked reduction in the immunologic
      accessibility of cytoplasmic and nuclear STAT3 and STAT5 within 20 to 30 min that
      lasted 2 to 4 h (STAT-masking) provided that the cells had been previously
      cultured at 32.5 degrees C for at least 18 to 20 h. The onset of IL-6-induced
      STAT-masking required protein tyrosine kinase, protein tyrosine phosphatase,
      proteasomal, phospholipase C, and mitogen-activated protein kinase kinase 1
      activities. The maintenance of IL-6-induced STAT-masking was dependent on
      continued signaling through the phosphatidylinositol-dependent phospholipase C
      pathway. Despite a reduction in IL-6-induced STAT3 DNA binding activity in the
      nuclear compartment during STAT-masking, there was increased and prolonged
      accumulation of tyrosine-phosphorylated STAT3 in both the cytoplasmic and nuclear
      compartments, indicating that the capacity of tyrosine-phosphorylated STAT3 to
      bind DNA was reduced during STAT-masking. Thus, IL-6-induced STAT-masking, as
      dramatically evident on immunomicroscopy, is a visible consequence of a novel
      cellular process by which a p53-Val135-induced gene product(s) regulates the
      association of masking protein(s) with and the DNA-binding capacity of STAT3.

PMID- 9647241
TI  - Differences between B cell and macrophage transformation by the bovine parasite,
      Theileria annulata: a clonal approach.
AB  - Theileria annulata, a tick-transmitted protozoan parasite, infects and transforms
      cells of the hemopoietic system, particularly those of the B cell and
      monocyte/macrophage lineages. Here, the effect of infection/transformation on the
      resulting phenotype was studied using a clonal approach. Three phenotypes of
      transformed cell lines could be discerned. The first is characterized by surface
      expression of IgM, CD21, and the B cell epitopes, B-B2 and B-B8, Ig heavy chain
      gene rearrangement, and mRNA expression. Such lines were obtained from fresh and
      cultured PBMC and at increased frequency from purified B cells, but never from
      fetal bone marrow cells. The second phenotype can be distinguished from the first
      by the absence of Ig heavy chain expression and reduced surface expression of B
      cell markers (CD21, B-B2, B-B8). Clones with this phenotype were obtained from
      transformed fetal bone marrow cells only. The third phenotype showed an absence
      of all of the above B cell markers, including surface IgM, and a lack of Ig heavy
      chain gene rearrangement. The latter clones could be maintained for several weeks
      after elimination of T. annulata by BW720c treatment, and they reacquired a
      macrophage-like phenotype. This implies that parasite-induced dedifferentiation
      is restricted to monocyte/macrophage, and that B cell markers are indicative of
      cell lineage progeny. Demonstration of surface IgM on PBMC-derived B cell clones
      suggests that infection of B cells with T. annulata may be an epigenetic method
      to immortalize ruminant B cells of a defined Ag specificity.

PMID- 9647242
TI  - Reduced tumorigenicity and augmented leukocyte infiltration after monocyte
      chemotactic protein-3 (MCP-3) gene transfer: perivascular accumulation of
      dendritic cells in peritumoral tissue and neutrophil recruitment within the
      tumor.
AB  - Monocyte chemotactic protein-3 (MCP-3) is a C-C chemokine that interacts with the
      CCR1, CCR2, and CCR3 receptors and has a spectrum of action encompassing T cells,
      NK cells, eosinophils, and dendritic cells (DC), in addition to mononuclear
      phagocytes. This broad spectrum of action prompted the present study aimed at
      assessing the antitumor activity of MCP-3 in a gene transfer approach and at
      providing information as to the actual in vivo leukocyte recruiting capacity of
      MCP-3. P815 mastocytoma cells transfected with the gene coding MCP-3 (P815/MCP-3)
      grew in syngeneic hosts and underwent rejection. Rejection was associated with
      profound alterations of leukocyte infiltration and resistance to subsequent
      challenge with P815 cells. Tumor-associated macrophages, already present in
      copious numbers, T cells, eosinophils, and neutrophils, increased in tumor
      tissues after gene transfer. DC, identified as DEC205+, high MHC class II+,
      CD11c+ cells, did not increase substantially in the tumor mass. However, in
      peritumoral tissues, DC accumulated in perivascular areas. P815/MCP-3-transfected
      tumor cells grew normally in nude mice. Increased accumulation of macrophages and
      polymorphonuclear neutrophils was evident also in nude mice. mAb against CD4,
      CD8, and IFN-gamma, but not against IL-4, inhibited rejection of MCP-3-producing
      cells. An anti-polymorphonuclear mAb caused only a retardation of MCP-3-elicited
      tumor rejection. Thus, MCP-3 gene transfer elicits tumor rejection by activating
      type I T cell-dependent immunity. It is tempting to speculate that altered
      trafficking of APCs, which express receptors and respond to MCP-3, together with
      recruitment of activated T cells, underlies activation of specific immunity by
      MCP-3-transfected cells.

PMID- 9647243
TI  - A longitudinal study of type-specific antibody responses to Plasmodium falciparum
      merozoite surface protein-1 in an area of unstable malaria in Sudan.
AB  - Merozoite surface protein-1 (MSP-1) of Plasmodium falciparum is a malaria vaccine
      candidate Ag. Immunity to MSP-1 has been implicated in protection against
      infection in animal models. However, MSP-1 is a polymorphic protein and its
      immune recognition by humans following infection is not well understood. We have
      compared the immunogenicity of conserved and polymorphic regions of MSP-1, the
      specificity of Ab responses to a polymorphic region of the Ag, and the duration
      of these responses in Sudanese villagers intermittently exposed to P. falciparum
      infections. Recombinant Ags representing the conserved N terminus (Block 1), the
      conserved C terminus, and the three main types of the major polymorphic region
      (Block 2) of MSP-1 were used to determine the specificity and longitudinal
      patterns of IgG Ab responses to MSP-1 in individuals. Abs from 52 donors were
      assessed before, during, and after malaria transmission seasons for 4 yr. Ags
      from the Block 1 region were rarely recognized by any donor. Responses to the C
      terminal Ag occurred in the majority of acutely infected individuals and thus
      were a reliable indicator of recent clinical infection. Ags from the polymorphic
      Block 2 region of MSP-1 were recognized by many, although not all individuals
      after clinical malaria infections. Responses to Block 2 were type specific and
      correlated with PCR typing of parasites present at the time of infection.
      Responses to all of these Ags declined within a few months of drug treatment and
      parasite clearance, indicating that naturally induced human Ab responses to MSP-1
      are short lived.

PMID- 9647244
TI  - Susceptibility to Pneumocystis carinii in mice is dependent on simultaneous
      deletion of IFN-gamma and type 1 and 2 TNF receptor genes.
AB  - Pneumocystis carinii pneumonia is an important cause of morbidity and mortality
      in immunosuppressed patients, particularly HIV-infected individuals. An improved
      understanding of pulmonary host response, including the cytokines required for
      defense, could suggest novel immunotherapeutic approaches to this infection. The
      cytokines IFN-gamma and TNF have contributory roles in host defense against P.
      carinii, but their combined and interactive importance is unclear. To test the
      roles of these cytokines in defense against P. carinii directly, organisms were
      inoculated intratracheally into wild-type mice and into three groups of gene
      deleted mice: those lacking genes for IFN-gamma (IFN-gamma(-/-)), for TNF
      receptors 1 and 2 (TNFR(-/-)), and for both IFN-gamma and TNFR (TNFR-IFN-gamma(-/
      )). Four weeks after P. carinii inoculation, lungs of the wild-type, IFN-gamma(-/
      ), and TNFR(-/-) mice demonstrated clearance of P. carinii and only mild
      inflammation. However, TNFR-IFN-gamma(-/-) mice demonstrated severe P. carinii
      infection and lung inflammation. Our findings demonstrate conclusively that
      deletion of either IFN-gamma or TNF activity alone does not block clearance of P.
      carinii. However, simultaneous deletion of IFN-gamma and TNF receptor genes
      results in susceptibility to P. carinii. Rather than focusing exclusively on
      individual cytokines, our data suggest that immunotherapy targeted at maximizing
      both the IFN-gamma and TNF responses to P. carinii may be required to augment
      host defense against this important opportunistic pathogen.

PMID- 9647245
TI  - Stability of virus-specific CD4+ T cell frequencies from acute infection into
      long term memory.
AB  - Mice infected with viruses develop long-lasting high frequency memory CD8+ T cell
      pools, but much less is known about the CD4+ T cell response. FACS analysis
      revealed the modulation of several activation markers on CD4+ T cells during an
      acute infection with lymphocytic choriomeningitis virus (LCMV), consistent with
      an activated cell phenotype. Examination of virus-specific cytokine production
      using ELISPOT assays showed a significant increase in the number of IFN-gamma
      secreting cells in the spleen during an acute LCMV infection. CD8+ T cells made
      up the majority of the IFN-gamma-producing cells, but analysis of the cell
      culture supernatants by ELISA showed that the CD4+ T cells produced more IFN
      gamma on a per cell basis. Using limiting dilution assays, we examined the CD4+ T
      cell precursor (Thp) frequency in C57BL/6 mice infected with LCMV. The virus
      specific Thp frequency increased from <1/100,000 in uninfected mice to a peak of
      approximately 1/600 in purified splenic CD4+ T cell populations by 10 days
      postinfection with LCMV. After the peak of the response, the Thp frequency
      decreased only about twofold per CD4+ T cell to approximately 1/1200 and remained
      stable into long term memory. In contrast to the highly activated CD4+ T cells
      recovered during the acute LCMV infection, the memory CD4+ T cells were
      maintained at a lower activation state as judged by cell size and ability to
      secrete IFN-gamma. Thus, like the CD8+ T cell frequencies, the CD4+ T cell
      frequencies remain elevated after the acute infection subsides and stay elevated
      throughout long term immunity.

PMID- 9647246
TI  - Antigen-specific cytolysis by neutrophils and NK cells expressing chimeric immune
      receptors bearing zeta or gamma signaling domains.
AB  - TCR- and IgG-binding Fc receptors (Fc gamma R) mediate a variety of critical
      biologic activities including cytolysis via the structurally related zeta- and
      gamma-chains. In previous studies, we have described chimeric immune receptors
      (CIR) in which the ligand-binding domain of a heterologous receptor or Ab is
      fused directly to the cytoplasmic domain of the TCR zeta-chain. Such zeta-CIRs
      efficiently trigger cytotoxic function of both T and NK cells in a target
      specific manner. In this report, we compared the ability of both zeta- and gamma
      CIRs to activate the cytolytic function of two distinct classes of Fc gamma R
      bearing effectors, NK cells and neutrophils. Mature neutrophils expressing zeta-
      and gamma-CIR were generated in vivo from murine hemopoietic stem cells following
      transplantation of syngeneic mice with retrovirally transduced bone marrow or in
      vitro from transduced human CD34+ progenitors following differentiation. Both
      zeta- and gamma-based CIRs were capable of activating target-specific cytolysis
      by both NK cells and neutrophils, although the zeta-CIR was consistently more
      efficient. The experimental approach described is a powerful one with which to
      study the role of nonlymphoid effector cells in the host immune system and
      permits the rational design of immunotherapeutic strategies that rely on
      harnessing multiple immune cell functions via CIR-modified hemopoietic stem cells
      or progenitors.

PMID- 9647247
TI  - Galectin-3 down-regulates IL-5 gene expression on different cell types.
AB  - Galectin-3 is an animal lectin, formerly named epsilon-binding protein or Mac-2,
      which has been described to play an important role in some inflammatory processes
      by the implication of different cells and the increase in cell adhesion functions
      through laminin binding activity. In this work we analyzed the role of galectin-3
      in the modulation of Th2 cytokines that have an important role in the development
      of the inflammatory response. We have found that the addition of galectin-3 to
      human eosinophils, the eosinophilic cell line EoL-3, PBMC, and an Ag-specific T
      cell line (CD4+) produced a selective inhibition of IL-5 transcription. No
      inhibitory effect was found on the IL-4 mRNA transcription rate. The inhibitory
      effect on IL-5 transcription was reversed by incubation with lactose and using
      specific Ab against galectin-3. Galectin-3 is able to induce inhibition of the IL
      5 released in the supernatants from PBMC stimulated with phorbol 12,13-dibutyrate
      and anti-CD3. Similar results were obtained when a T-specific cell line was
      stimulated with Ag. Also, EoL-3 stimulated with anti-CD32 produced IL-5 protein,
      the synthesis of which was partially inhibited by galectin-3. The present results
      demonstrate that galectin-3 induces a selective down-regulation of IL-5
      expression in different cell types, opening important new possibilities in the
      regulation of the allergic reactions.

PMID- 9647248
TI  - Cooperation of both TNF receptors in inducing apoptosis: involvement of the TNF
      receptor-associated factor binding domain of the TNF receptor 75.
AB  - TNF-R55 is the main receptor mediating TNF-induced cytotoxicity. However, in some
      cells TNF-R75 also signals cell death. In PC60 cells, the presence of both
      receptor types is required to induce apoptosis following either specific TNF-R55
      or TNF-R75 triggering, pointing to a mechanism of receptor cooperation. In this
      study, we extend previous observations and show that TNF-R55 and TNF-R75
      cooperation in the case of apoptosis in PC60 cells is bidirectional. We also
      demonstrate ligand-independent TNF-R55-mediated cooperation in TNF-R75-induced
      granulocyte/macrophage-CSF secretion, but not vice versa. To determine which part
      of the intracellular TNF-R75 sequence was responsible for the observed receptor
      cooperation in apoptosis, we introduced different TNF-R75 mutant constructs in
      PC60 cells already expressing TNF-R55. Our data indicate that an intact TNF-R
      associated factors 1 and 2 (TRAF1/TRAF2)-binding domain is required for receptor
      cooperation. These findings suggest a role for the TRAF complex in TNF-R
      cooperation in the induction of cell death in PC60 cells. Nevertheless,
      introduction of a dominant negative (DN) TRAF2 molecule was not able to affect
      receptor cooperation. Remarkably, TRAF2-DN overexpression, which was found to
      inhibit the TNF-dependent recruitment of endogenous wild-type TRAF2 to the TNF
      R75 signaling complex, could neither block TNF-R55- or TNF-R75-induced NF-kappaB
      activation nor granulocyte/macrophage-CSF secretion. Possibly, additional factors
      different from TRAF2 are involved in TNF-mediated NF-kappaB activation.

PMID- 9647249
TI  - Differential expression and function of L-selectin on CD56bright and CD56dim
      natural killer cell subsets.
AB  - NK cells are the first line of defense against foreign cells, virally infected
      cells, and tumors. The mechanisms whereby NK cells accumulate in extralymphoid
      sites in response to pathogenic stimuli are not well understood. The L-selectin
      adhesion molecule (CD62L) plays a primary role in mediating the initial
      interaction of leukocytes with vascular endothelium, a crucial step in the
      extravasation of immune effector cells into tissues. In this report, we show L
      selectin to be uniquely expressed on a subset of resting human NK cells
      (CD56bright). Notably, CD56bright NK cells expressed L-selectin at a higher
      density than all other peripheral blood leukocytes. NK activation by PMA, IL-2,
      IL-15, or TGF-beta down-regulated L-selectin on the CD56bright subset, while
      increased L-selectin levels were observed in both the CD56bright and CD56dim NK
      subsets in response to IL-12, IL-10, or IFN-alpha. Moreover, CD56bright NK cells
      bound with high efficiency to physiologic L-selectin ligands on peripheral lymph
      node high endothelial venules (HEV). In sharp contrast, CD56dim NK cells adhered
      poorly to HEV and were predominantly L-selectin- or expressed L-selectin only at
      low density. In CD56bright cells and a subpopulation of CD56dim cells, L-selectin
      ligation by mAb cross-linking activated lymphocyte function-associated Ag 1 (LFA
      1), a second adhesion molecule required for leukocyte extravasation. LFA-1 was
      expressed on both NK subsets, although its density was constitutively higher on
      CD56dim cells. Taken together, evidence of differential expression of L-selectin
      and LFA-1 on CD56bright and CD56dim NK subsets strongly suggests unique migratory
      properties and functions of these cells during the early immune response to
      foreign pathogens.

PMID- 9647250
TI  - Enhancing effect of IL-17 on IL-1-induced IL-6 and leukemia inhibitory factor
      production by rheumatoid arthritis synoviocytes and its regulation by Th2
      cytokines.
AB  - IL-17 is a cytokine produced by CD4 T cells that activates the production of
      inflammatory mediators by synoviocytes. To study the contribution of soluble
      factors in the interaction between T cells and synoviocytes in rheumatoid
      arthritis (RA), we looked at the effect of IL-17 on these cells in the presence
      of cytokines classified as pro (IL-1)- and anti-inflammatory (IL-4, IL-13, IL
      10). Both human rIL-1beta and rIL-17 induced IL-6 and leukemia inhibitory factor
      (LIF) production by synovial fibroblasts in a dose-dependent manner. After 7 days
      of culture, optimal concentrations of IL-1beta increased IL-6 (33-fold) and LIF
      (10-fold) production by synoviocytes, while IL-17 showed a lesser effect on IL-6
      (17-fold) and LIF (4-fold) production. Using low concentrations of IL-17 and IL
      1beta in combination, a synergistic effect was observed on the production of IL
      6, whereas an additive effect was observed for LIF production. Production of
      biologically active IL-17 was demonstrated in RA synovium supernatants with the
      use of a blocking anti-IL-17 Ab. Both IL-4 and IL-13 had a modest stimulatory
      effect on IL-1- and IL-17-induced production of IL-6, but inhibited that of LIF.
      In contrast, IL-10 had a limited inhibitory effect on IL-6 production and no
      effect on that of LIF. These findings indicate that low levels of cytokines
      produced by monocytes (IL-1) and T cells (IL-17) can act together on
      synoviocytes. Thus, some RA synovium T cells producing IL-17 can activate
      mesenchymal cells leading to an increased proinflammatory pattern sensitive to
      Th2 cytokine regulation.

PMID- 9647251
TI  - Human eosinophils produce biologically active IL-12: implications for control of
      T cell responses.
AB  - The present study assessed the capacity of eosinophils (EOS) to synthesize the
      cytokine IL-12. Blood-derived, highly purified human EOS from six atopic patients
      and two nonatopic individuals were treated in culture with IL-4, IL-5,
      granulocyte-macrophage CSF, IFN-gamma, TNF-alpha, IL-1alpha, RANTES, and
      complement 5a, respectively. The expression of both IL-12 protein and mRNAs for
      the p35 and p40 IL-12 subunits was strongly induced in all donors by the Th2-like
      cytokines IL-4 and granulocyte-macrophage CSF and was also moderately induced by
      TNF-alpha and IL-1alpha. IL-5 treatment resulted in IL-12 synthesis in four
      atopic donors and one nonatopic donor, whereas IFN-gamma induced IL-12 synthesis
      in only two atopic donors. In contrast, RANTES exclusively induced mRNA for the
      p40 subunit without detectable protein release, and complement 5a had no effect
      on IL-12 mRNA or protein expression. EOS-derived IL-12 was biologically active,
      because supernatants derived from IL-4-treated EOS superinduced the Con A-induced
      expression of IFN-gamma by a human Th1-like T cell line. This activity was
      neutralized by anti-IL-12 Abs. In conclusion, EOS secrete biologically active IL
      12 after treatment with selected cytokines, which mainly represent the Th2-like
      type. Consequently, EOS may promote a switch from Th2-like to Th1-like immune
      responses in atopic and parasitic diseases.

PMID- 9647253
TI  - Angiotensin II participates in mononuclear cell recruitment in experimental
      immune complex nephritis through nuclear factor-kappa B activation and monocyte
      chemoattractant protein-1 synthesis.
AB  - Angiotensin-converting enzyme (ACE) inhibitors reduce macrophage infiltration in
      several models of renal injury. We approached the hypothesis that angiotensin II
      (AngII) could be involved in inflammatory cell recruitment during renal damage
      through the synthesis of monocyte chemoattractant protein-1 (MCP-1). In a model
      of immune complex nephritis, we observed an up-regulation of renal MCP-1 (mRNA
      and protein) coincidentally with mononuclear cell infiltration that were markedly
      reduced by treatment with the ACE inhibitor quinapril. Exposure of cultured rat
      mesangial cells to AngII increased MCP-1 mRNA expression (2.7-fold) and synthesis
      (3-fold), similar to that observed with TNF-alpha. Since NF-kappaB is involved in
      the regulation of MCP-1 gene, we explored whether the effects of AngII were
      mediated through NF-kappaB activation. Untreated nephritic rats showed increased
      renal NF-kappaB activity (3.5-fold) that decreased in response to ACE inhibition.
      In mesangial cells, AngII activated NF-kappaB (4.3-fold), and the NF-kappaB
      inhibitor pyrrolidine dithiocarbamate abolished the AngII-induced NF-kappaB
      activation and MCP-1 gene expression. Our results suggest that AngII could
      participate in the recruitment of mononuclear cells through NF-kappaB activation
      and MCP-1 expression by renal cells. This could be a novel mechanism that might
      further explain the beneficial effects of ACE inhibitors in progressive renal
      diseases.

PMID- 9647252
TI  - A synthetic CD4-CDR3 peptide analog enhances skin allograft survival across a MHC
      class II barrier.
AB  - The efficacy of a synthetic peptide analogue (rD-mPGPtide), mimicking the CDR3
      region in the first domain of the CD4 surface molecule, was investigated in a
      murine model for CD4+ T cell-mediated skin allograft rejection. A single
      injection of rD-mPGPtide shortly before transplantation exhibited significantly
      prolonged graft survival in the B6 anti-B6.C-H2bm12 MHC class II-disparate strain
      combination. Long-term graft survival (>100 days) was achieved when thymectomized
      adult recipient mice were transplanted along with rD-mPGPtide treatment. The
      peptide also affected secondary rechallenge responses with MHC class II
      allografts. In addition, the inhibitory effect of the rD-mPGPtide in this
      transplantation model was directed against CD4+ T cells and was exclusively
      specific toward donor alloantigen. In vitro analysis of CD4+ T cells isolated
      from the draining lymph nodes of rD-mPGPtide-treated recipients indicated a 450
      fold decrease in precursor frequency in response to donor allostimulation
      compared with the untreated control group. There was also significant down
      regulation of the frequency of IL-2-, IFN-gamma-, and IL-4-producing CD4+ T cells
      upon in vitro allogeneic restimulation of host cells 4 days posttransplantation.
      However, these same CD4+ T cells maintained the capacity to produce normal
      cytokine levels upon third-party allostimulation. Thus, these studies demonstrate
      that a CD4-CDR3 peptide analogue can specifically and effectively prolong skin
      graft survival across MHC class II barriers.

PMID- 9647254
TI  - Hemorrhagic shock primes for increased expression of cytokine-induced neutrophil
      chemoattractant in the lung: role in pulmonary inflammation following
      lipopolysaccharide.
AB  - Recent studies have suggested that hemorrhagic shock followed by resuscitation
      renders patients more susceptible to lung injury by priming for an exaggerated
      response to a second stimulus, the so-called "two-hit" hypothesis. We
      investigated the role of C-X-C chemokines in mediating the augmented lung
      inflammation in response to LPS following resuscitated shock. In a rodent model,
      animals exposed to antecedent shock exhibited enhanced lung neutrophil
      sequestration and transpulmonary albumin flux in response to intratracheal LPS.
      This effect correlated with an exaggerated expression of cytokine-induced
      neutrophil chemoattractant (CINC) protein and mRNA, but not macrophage
      inflammatory protein 2. Strategies designed to inhibit CINC, both anti-CINC Ab
      and supplementation with the antioxidant N-acetyl-cysteine, prevented the
      enhanced neutrophil sequestration, suggesting that CINC played a central role in
      the enhanced leukocyte accumulation following shock plus LPS treatment. Shock
      alone increased lung nuclear factor-kappaB expression and augmented the response
      to LPS. Prevention of this effect by N-acetylcysteine supplementation of the
      resuscitation fluid implicates a role for oxidant stress in the priming for lung
      inflammation following shock. Finally, alveolar macrophages recovered from shock
      resuscitated animals released more CINC protein in vitro in response to LPS than
      macrophages from sham animals. Considered together, these findings show that
      augmented release of CINC, in part from primed alveolar macrophages, contributes
      significantly to the enhanced lung leukosequestration and transpulmonary albumin
      flux in response to LPS following resuscitated shock.

PMID- 9647255
TI  - T cell epitopes in Japanese cedar (Cryptomeria japonica) pollen allergens: choice
      of major T cell epitopes in Cry j 1 and Cry j 2 toward design of the peptide
      based immunotherapeutics for the management of Japanese cedar pollinosis.
AB  - Japanese cedar pollinosis is caused by exposure to Japanese cedar (Cryptomeria
      japonica) pollen, of which two components, Cry j 1 and Cry j 2, are believed to
      be the major allergens. T cell lines specific to either Cry j 1 or rCry j 2 were
      reactive to various portions of each panel of overlapping peptides derived from
      Cry j 1 or Cry j 2. Two peptides, p211-225 and p108-120, from among six major T
      cell epitopes identified in Cry j 1 sequence, and three peptides, p182-200, p344
      355, and p66-80, from among five in Cry j 2, were chosen to design an artificial
      polypeptide (named Cry-consensus) based on a difference among the types of the
      restriction molecules capable of presenting these peptides. After construction of
      a DNA encoding these peptides in order, Cry-consensus was expressed in
      Escherichia coli. Five of six T cell epitopes, except for Cry j 2 p344-355, in
      Cry-consensus were recognized by the T cell clones specific to each peptide. PBMC
      from allergic patients induced higher proliferation under stimulation from Cry
      consensus than individual peptides. Eighty-eight percent of the PBMC (15 of 17)
      showed proliferation under the Cry-consensus stimulation. Thus, several major T
      cell epitopes from Cry j 1 and Cry j 2 can be chosen in the design of peptide
      based immunotherapeutics for the management of Japanese cedar pollinosis in
      subjects having various types of HLA class II molecules.

PMID- 9647256
TI  - Ubiquitination and dimerization of complement receptor type 2 on sheep B cells.
AB  - Complement receptor type 2 (CR2) is a membrane-anchored glycoprotein that
      specifically binds C3d, as well as other ligands, and plays diverse roles in
      regulating immunity. Here we show that two distinct isoforms of CR2 are expressed
      on the surface of sheep B lymphocytes. One (CR2no 150 kDa) is structurally
      similar to known mammalian homologues while the other (CR2ub 190 kDa) has been
      modified by the covalent attachment of ubiquitin to the cytoplasmic domain and is
      identified for the first time. CR2no and CR2ub are expressed on the surface of
      sheep B cells as noncovalently associated dimers and the external topography of
      the two isoforms differs in some respect. The basis for these unusual higher
      order structural properties may lie in the primary sequence of sheep CR2, since
      the transmembrane domain contains a region resembling a rare 7-amino acid
      dimerization motif, and two lysine residues in the cytoplasmic domain provide
      potential sites for posttranslational ubiquitination. The primary structures of
      sheep ubiquitin and C3d ligand are extensively conserved. In conjunction with the
      results of separate in vivo studies, these findings suggest that selective
      ubiquitination plays a role in modulating the higher-order structure and/or
      expression of CR2 during B cell development.

PMID- 9647257
TI  - SB 203580 inhibits p38 mitogen-activated protein kinase, nitric oxide production,
      and inducible nitric oxide synthase in bovine cartilage-derived chondrocytes.
AB  - Nitric oxide (NO) is implicated in a number of inflammatory processes and is an
      important mediator in animal models of rheumatoid arthritis and in in vitro
      models of cartilage degradation. The pyridinyl imidazole SB 203580 inhibits p38
      mitogen-activated protein (MAP) kinase in vitro, blocks proinflammatory cytokine
      production in vitro and in vivo, and is effective in animal models of arthritis.
      The purpose of this study was to determine whether SB 203580 could inhibit p38
      MAP kinase activity, NO production, and inducible NO synthase (iNOS) in IL-1
      stimulated bovine articular cartilage/chondrocyte cultures. The results indicated
      that SB 203580 inhibited both IL-1 stimulated p38 MAP kinase activity in isolated
      chondrocytes and NO production in bovine chondrocytes and cartilage explants with
      an IC50 value of approximately 1 microM. To inhibit NO production, SB 203580 had
      to be present in cartilage explant cultures during the first 8 h of IL-1
      stimulation, and activity was lost when it was added 24 h following IL-1. SB
      203580 did not inhibit iNOS activity, as measured by the conversion of arginine
      to citrulline, when added directly to cultures where the enzyme had already been
      induced, but had to be present during the induction period. Using a 372-bp probe
      for bovine iNOS we demonstrated inhibition of IL-1-induced mRNA by SB 203580 at
      both 4 and 24 h following IL-1 treatment. The iNOS mRNA levels were consistent
      with NO levels in 24-h cell culture supernatants of the IL-1-stimulated bovine
      chondrocytes used to obtain the RNA.

PMID- 9647258
TI  - Systemic administration of endotoxin induces bronchopulmonary hyperreactivity
      dissociated from TNF-alpha formation and neutrophil sequestration into the murine
      lungs.
AB  - Bronchopulmonary hyperreactivity (BHR), an increased responsiveness to
      nonspecific bronchoconstrictor agents, is a well-known characteristic of
      bronchial asthma. It has been recently suggested that the severity of this
      disease is related to the endotoxin content of house dust. In the present report,
      it is shown that the i.p. administration of bacterial LPS to mice is followed by
      a marked early dose-dependent BHR in response to methacholine. The microscopic
      examination showed no ultrastructural lesions of the lungs or of the airways, but
      a marked neutrophil accumulation in the capillaries, as confirmed by an increase
      of the lung content in the neutrophil enzyme marker myeloperoxidase. In parallel,
      high levels of TNF-alpha were found in plasma as well as its transcripts in the
      lung tissues. Using immunologic (anti-TNF-alpha and anti-granulocyte Abs), and
      pharmacologic (dexamethasone and vinblastine) tools, it is demonstrated that BHR
      is apparently neither related to the presence of neutrophils in the pulmonary
      microvasculature nor to the synthesis of TNF-alpha.

PMID- 9647259
TI  - Demonstration of human T lymphotropic virus type I (HTLV-I) tax-specific CD8+
      lymphocytes directly in peripheral blood of HTLV-I-associated myelopathy/tropical
      spastic paraparesis patients by intracellular cytokine detection.
AB  - Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic
      paraparesis (HAM/TSP) is an inflammatory neurologic disease caused by HTLV-I
      infection and has been associated with elevated levels of several proinflammatory
      cytokines in both serum and cerebrospinal fluid. It is unknown what kind of cells
      secrete these cytokines and if HTLV-I Ags are associated with this phenomenon.
      Here, we investigated the expression of cytokines in PBL from eight HAM/TSP
      patients, nine HTLV-I-infected asymptomatic carriers, and seven healthy controls
      by flow cytometry combined with intracellular cytokine staining. PBL were
      cultured with brefeldin A without mitogen and IL-2 for 14 h. Under these
      conditions, CD8+ cells produced proinflammatory cytokines including IFN-gamma,
      TNF-alpha, and IL-2, which were significantly elevated in HAM/TSP patients. The
      proportion of CD8+ cells producing IFN-gamma in HAM/TSP patients, asymptomatic
      carriers, and healthy controls were, on average, 4.9, 0.4, and 0.3%,
      respectively. IFN-gamma production by these CD8+ cells was suppressed by anti-HLA
      class I Ab. Purified CD8+ cells from an HLA-A2 HAM/TSP patient produced IFN-gamma
      by cocultivation with autologous CD4 cells, the main reservoir of HTLV-I in vivo,
      or allogenic HLA-A2+ B cells pulsed with a known immunodominant HTLV-I tax
      peptide. These data suggest that high levels of circulating HTLV-I-specific CD8+
      T lymphocytes have the potential to produce proinflammatory cytokines and may
      promote inflammatory responses to HTLV-I in HAM/TSP patients.

PMID- 9647260
TI  - Lymphocyte activation gene-3 (LAG-3) expression and IFN-gamma production are
      variably coregulated in different human T lymphocyte subpopulations.
AB  - We evaluated the relationship between cytokine profile and the expression of the
      lymphocyte activation gene-3 (LAG-3) in both T cell clones and polyclonal T cell
      lines; LAG-3 is a CD4-like protein whose expression is reportedly restricted to
      Th1/0 cells and dependent upon IFN-gamma. We found that, while LAG-3 was
      expressed only by CD4+ T cell clones producing IFN-gamma, most CD8+ clones
      producing IL-4 but not IFN-gamma (i.e., with a T cytotoxic-2-like profile) were
      LAG-3+. The intensity of LAG-3 expression by CD8+ clones correlated with the
      amount of released IFN-gamma, suggesting that this cytokine is not required for
      expression but rather for the up-regulation of LAG-3. Flow cytometric analyses of
      polyclonal T cell lines confirmed that LAG-3 could be expressed by both CD4+ and
      CD8+ cells that did not contain cytoplasmic IFN-gamma. In these cell lines, large
      proportions of CD4+ and CD8+ cells coexpressed LAG-3 and CD30, a putative marker
      of Th2-like cells. Overall, our data do not support the earlier suggestion that
      LAG-3 and CD30 are selective markers of T cells with type-1 and type-2 cytokine
      profiles, respectively.

PMID- 9647261
TI  - IFN-gamma receptor signaling is essential for the initiation, acceleration, and
      destruction of autoimmune kidney disease in MRL-Fas(lpr) mice.
AB  - CSF-1 and TNF-alpha in the kidney of MRL-Fas(lpr) mice are proximal events that
      precede and promote autoimmune lupus nephritis, while apoptosis of renal
      parenchymal cells is a feature of advanced human lupus nephritis. In the MRL
      Fas(lpr) kidney, infiltrating T cells that secrete IFN-gamma are a hallmark of
      disease. To examine the impact of IFN-gamma on renal injury in MRL-Fas(lpr) mice,
      we constructed a IFN-gamma R-deficient strain. In MRL-Fas(lpr) mice lacking IFN
      gamma R, circulating and intrarenal CSF-1 were absent, TNF-alpha was markedly
      reduced, survival was extended, lymphadenopathy and splenomegaly were prevented,
      and the kidneys remained protected from destruction. Mesangial cells (MC) that
      were signaled through the IFN-gamma R induced CSF-1 and TNF-alpha in MRL-Fas(lpr)
      mice. We detected a large number of apoptotic renal parenchymal cells in advanced
      nephritis and determined that signaling via the IFN-gamma R induces apoptosis of
      tubular epithelial cells (TEC), but not MC. By comparison, TNF-alpha induces
      apoptosis in MC, but not TEC, of the MRL-Fas(lpr) strain. Thus, IFN-gamma is
      directly and indirectly responsible for apoptosis of TEC and MC in MRL-Fas(lpr)
      mice, respectively. In conclusion, IFN-gamma R signaling is essential for the
      initiation (CSF-1), acceleration (CSF-1 and TNF-alpha), and apoptotic destruction
      of renal parenchymal cells in MRL-Fas(lpr) autoimmune kidney disease.

PMID- 9647262
TI  - Experimental autoimmune encephalomyelitis induced with a combination of myelin
      basic protein and myelin oligodendrocyte glycoprotein is ameliorated by
      administration of a single myelin basic protein peptide.
AB  - Multiple sclerosis is an autoimmune disease of the central nervous system in
      which T cell reactivity to several myelin proteins, including myelin basic
      protein (MBP), proteolipid protein, and myelin oligodendrocyte glycoprotein
      (MOG), has been implicated in the perpetuation of the disease state. Experimental
      autoimmune encephalomyelitis (EAE) is used commonly as a model in which potential
      therapies for multiple sclerosis are evaluated. The ability of T cell epitope
      containing peptides to down-regulate the disease course is well documented for
      both MBP- and proteolipid protein-induced EAE, and recently has been shown for
      MOG-induced EAE. In this study, we describe a novel EAE model, in which
      development of severe disease symptoms in (PL/J x SJL)F1 mice is dependent on
      reactivity to two different immunizing Ags, MBP and MOG. The disease is often
      fatal, with a relapsing/progressive course in survivors, and is more severe than
      would be predicted by immunization with either Ag alone. The MOG plus MBP disease
      can be treated postinduction with a combination of the MOG 41-60 peptide
      (identified as the major therapeutic MOG epitope for this strain) and the MBP Ac1
      11[4Y] peptide. A significant treatment effect can also be obtained by
      administration of the MBP peptide alone, but this effect is strictly dose
      dependent. This MBP peptide does not treat the disease induced only with MOG.
      These results suggest that peptide immunotherapy can provide an effective means
      of mitigating disease in this model, even when the treatment is targeted to only
      one component epitope or one component protein Ag of a diverse autoimmune
      response.

PMID- 9647263
TI  - In vitro effects of IL-12 on HIV-1-specific CTL lines from HIV-1-infected
      children.
AB  - We studied the in vitro effects of IL-12 on HIV-1-specific CTL lines derived from
      PBMC of HIV-1-infected children. HIV-1-specific CTL lines were derived by
      limiting dilution following Ag-specific stimulation of PBMC from HIV-1-infected
      children and were maintained with repeated anti-CD3 stimulation. Following
      incubation with IL-12 for 5 to 7 days, HIV-1-specific cytotoxicity was augmented
      in a dose-dependent fashion (mean increase, 94 +/- 83 lytic units; p = 0.0006).
      Experiments performed with CD3-blocking Abs and MHC-mismatched targets
      demonstrated that the IL-12-enhanced activity was MHC restricted and dependent on
      cells bearing CD3. The effect of IL-12 on proliferation of the CTL lines as
      tested by [3H]TdR uptake was minimal, with stimulation indexes ranging from 1.25
      to 4.9. The effects of IL-12 on cytotoxicity were not significantly altered by
      addition of Ab to the IL-2R (anti-Tac) in quantities sufficient to block
      exogenous IL-2 (p = 0.15), demonstrating that endogenous IL-2 activity is not
      required for IL-12-enhanced cytolytic activity. Likewise, addition of
      neutralizing Ab specific for IFN-gamma did not change IL-12-enhanced cytotoxicity
      (p = 0.61). The in vivo role of IL-12 in the generation and the stimulation of
      CTL remains to be determined; however, its ability to augment HIV-1-specific CTL
      in vitro adds additional support for IL-12 as a candidate for immune-based
      therapy of HIV-1.

PMID- 9647264
TI  - C1 esterase inhibitor transfusions in patients with hereditary angioedema.

PMID- 9647265
TI  - Immunodeficiency with elevated IgM, lymphoid hyperplasia, autoimmune anemia, and
      thrombocytopenia.

PMID- 9647266
TI  - Insect stings.

PMID- 9647267
TI  - C1-esterase inhibitor transfusions in patients with hereditary angioedema.
AB  - BACKGROUND: Hereditary angioedema results from the deficiency of C1-esterase
      inhibitor (C1-INH), and C1-INH replacement would represent definitive treatment
      for angioedema attacks. In Canada, C1-INH is available only on a compassionate
      basis at select medical facilities. Our objective is to assess the efficacy of C1
      INH transfusions during angioedema attacks at a single Canadian institution.
      METHODS: A retrospective chart review of transfusion data between January 1, 1995
      and June 30, 1996 was performed. Phone interviews with patients elicited their
      opinions of the treatment. Data collected included the number and duration of
      angioedema attacks, dose of transfused C1-INH, and side effects of treatment.
      RESULTS: Of a cohort of 13 patients with hereditary angioedema, seven received
      transfusions with C1-INH. Attacks totaled 87, and more than 100,000 units of the
      product were transfused. The mean time for abatement of an attack after
      initiation of transfusion was 50 +/- 8 minutes (1 SD). There were no reports of
      adverse effects. Although patients were satisfied with the treatment, they raised
      concerns regarding long-term safety and availability. CONCLUSIONS: C1-INH
      transfusion is a satisfactory means of treating angioedema attacks.

PMID- 9647268
TI  - Efficacy, safety, and effects on quality of life of salmeterol versus albuterol
      in patients with mild to moderate persistent asthma.
AB  - BACKGROUND: Salmeterol xinafoate is a long-acting, highly selective, beta2
      adrenergic agonist that produces bronchodilation and clinically significant
      improvement in pulmonary function for up to 12 hours in patients with asthma.
      OBJECTIVE: To evaluate the impact on asthma-specific quality of life, efficacy,
      and safety of salmeterol versus albuterol in adult patients with mild-to-moderate
      persistent asthma. METHODS: A randomized, double-blind, double-dummy, parallel
      group, multicenter study was conducted in 539 adult asthma patients over 12
      weeks. Patients were randomized to receive either salmeterol 42 microg via
      metered-dose inhaler twice daily or albuterol 180 microg four times daily. Upon
      entry into the study, 46% of patients were being treated with an inhaled
      corticosteroid and were allowed to continue treatment throughout the study.
      Pulmonary function and asthma symptoms were monitored daily, and patients
      completed the Asthma Quality of Life Questionnaire (AQLQ) at baseline and after
      4, 8, and 12 weeks of treatment. RESULTS: Treatment with salmeterol twice daily
      produced significantly greater improvements from baseline in all quality of life
      domain ("Activity Limitation," "Asthma Symptoms," "Emotional Function,"
      "Environmental Exposure") scores and in the global AQLQ score at 12 weeks (P < or
      = .038) compared with albuterol treatment four times daily. Pulmonary function
      and asthma symptoms were also significantly improved with salmeterol compared
      with albuterol. CONCLUSIONS: Salmeterol 42 microg administered twice daily is
      significantly more effective than albuterol 180 microg four times daily for
      improving asthma-specific quality of life, controlling asthma symptoms, and
      improving pulmonary function in patients with mild-to-moderate persistent asthma.
      Furthermore, those improvements were maintained over a 12-week period.

PMID- 9647269
TI  - Northern blot identification of mRNA containing sequence for protein allergen,
      Alt a1, in eight strains of Alternaria alternata.
AB  - BACKGROUND: Concentrations of Alt a1, a major allergen from Alternaria alternata
      extracts, exhibit significant batch-to-batch variability. This variability may
      result from basic strain-related genetic differences or from environmental
      influences such as growth conditions or extraction methods. OBJECTIVE: The
      objective of this work is to determine if strain-to-strain allergen variability
      in Alternaria alternata, Alt a1 allergen occurs at the nucleic acid level.
      METHODS: We compared the content of mRNA for a segment known to contain sequence
      coding for the reported N-termini of this allergen in eight strains of Alternaria
      obtained from three individual sources grown under identical conditions. RNA was
      extracted from rapidly growing mycelia and analyzed by northern blot analysis for
      the content of a specific segment containing sequence for the Alt a1 allergen.
      Blots were also analyzed for the content of a specific 5.8S rRNA segment.
      RESULTS: The size of the mRNA for this protein was about 700 bases. Sequence for
      the specific segment was found in all of the eight strains tested. When
      normalized for extraction variabilities using the content of 5.8S rRNA, the
      calculated concentrations of Alt a1 mRNA of seven of the eight strains were
      similar. CONCLUSIONS: The results of these experiments suggest that this Alt a1
      related allergen sequence is found in many strains of Alternaria and that
      variabilities in allergen protein content noted previously result from
      posttranslational events.

PMID- 9647270
TI  - Clinical predictors of nasal secretory cell quantities in allergy clinic
      patients.
AB  - BACKGROUND: Nasal cytograms are useful in evaluating patients with inflammatory
      disease of the nose and paranasal sinuses. When mucosal samples are taken with
      curette and brush devices, significant numbers of non-leukocytic cells can also
      be analyzed. OBJECTIVE: To examine two specific morphologic variations in granule
      containing epithelial cells in nasal samples obtained from allergy clinic
      patients and describe their clinical associations. These two cellular variants
      consisted of goblet cells, with coalesced granules usually displacing the
      nucleus, and discrete granular mucinous cells (DGMC), which show more discrete
      granules not displacing the nucleus. METHODS: Patients from an adult allergy
      clinic were studied prospectively for nasal mucosal cytology, historical clinical
      data, nasal physical findings, serum IgE levels, and aeroallergen-specific IgE.
      Proportions and absolute numbers of goblet cells and DGMC in the nasal mucosal
      samples were related to other data using simple and multivariate analyses.
      RESULTS: Both goblet cells and DGMC showed absolute number increases in patients
      with observable nasal secretions. Discrete granular mucinous cell decreases were
      also observed in patients with IgE levels greater than or equal to 200 IU/mL and
      in asthmatic patients. In non-asthmatic patients with nasal eosinophilia, a
      significantly greater proportion of DGMC was observed compared with other
      patients (19.8 +/- 11.9% versus 8.5 +/- 5.9%, P = .007), while asthmatics with
      nasal eosinophilia had mean DGMC quantities closer to that observed in patients
      without nasal eosinophilia. Increases in goblet cell numbers were observed in
      patients with specific IgE to aeroallergens compared with other patients (46.5 +/
      46.7 versus 27.0 +/- 23.9, P = .014). Multivariate analysis confirmed that (1)
      the presence of aeroallergen-specific IgE and (2) the presence of nasal
      eosinophilia in the absence of asthma were differentially associated with
      increases in goblet cells and DGMC, respectively. CONCLUSIONS: Increases in nasal
      DGMC and goblet cells differentially relate to specific clinical patterns of
      nasal cellular inflammation and aeroallergen hypersensitivity. The nasal
      epithelial cell profile associated with nasal eosinophilia in asthmatics may
      differ from that observed in non-asthmatic nasal eosinophilia.

PMID- 9647271
TI  - Aquagenic urticaria: report of a case and review of the literature.
AB  - OBJECTIVE: To present a case of aquagenic urticaria and to review the literature
      regarding this very rare physical urticaria. METHOD: We described the clinical
      history of a patient with aquagenic urticaria. A water challenge test was
      performed, with plasma histamine levels measured before and after the challenge.
      RESULT: Our patient presented with a history of severe itching and wheals within
      five minutes of contact with water, regardless of its temperature or source (sea
      or tap water). A water challenge produced hives but serum histamine levels did
      not change. Prophylaxis with antihistamine or anticholinergic medications was not
      effective. CONCLUSION: Exposure to water can cause urticaria in susceptible
      patients and antihistamine and anticholinergic medication may not prevent the
      reaction. The mechanism of this phenomenon remains poorly understood.

PMID- 9647272
TI  - Eosinophils and pulmonary function: an epidemiologic study of adolescents and
      young adults.
AB  - BACKGROUND AND OBJECTIVE: In order to identify potential risk factors, other than
      cigarette smoking, for lung function impairment, the relationships of peripheral
      eosinophil count, bronchial responsiveness to inhaled histamine, skin test
      reactivity and respiratory symptoms to pulmonary function results in a population
      sample of 665 adolescents and young adults, aged 13 to 23 years. METHODS: Case
      history, especially concerning smoking habits and respiratory symptoms, was
      obtained by interview and a self administered questionnaire. Pulmonary function,
      peripheral blood eosinophil counts, bronchial responsiveness to inhaled histamine
      and skin test reactivity to common allergens were measured using standard
      techniques. The relationships of peripheral blood eosinophil counts, symptoms of
      asthma, cigarette smoking, bronchial responsiveness and skin test reactivity were
      compared with FEV1, adjusted for age, sex, and height. RESULTS: The peripheral
      eosinophil count was inversely correlated to FEV1 %predicted (P = .001); and
      subjects with eosinophilia (defined as > .25 x 10(9) l(-1)) had significantly
      reduced FEV1 %predicted compared with those without eosinophilia (95 +/- 13 %pred
      and 102 +/- 16 %predicted, respectively, P = .001). A close direct correlation
      was observed between blood eosinophils and histamine responsiveness (r = .60; P <
      .001). In nonatopic subjects (n = 382), the FEV1 %predicted was significantly
      lower in those with eosinophilia compared with those without. Subjects, who had
      never smoked, who were nonatopic and nonasthmatic, and who had no evidence of
      bronchial hyperresponsiveness, were found to have a weak but statistically
      significant inverse relation between eosinophil count and FEV1 %predicted (r = 
      .14, P = .04). In the same subgroup, subjects with eosinophilia (n = 27) had
      reduced FEV1 %predicted compared with those without (n = 177) (96 and 102,
      respectively, P < .05). CONCLUSIONS: The findings of this study support the
      theory that the role of the eosinophil leukocyte in obstructive pulmonary
      diseases extends beyond its role in allergic reactions, suggesting that an
      increased number of blood eosinophils reflects an inflammatory reaction in the
      airways, which might lead to development of obstructive airflow limitation.

PMID- 9647273
TI  - Comparison of three treatment regimens of inhaled sodium cromoglycate in the
      management of adult patients with severe, steroid-dependent asthma.
AB  - BACKGROUND: Asthmatic patients whose asthma remains poorly controlled despite
      treatment with high doses of inhaled corticosteroids and co-administration of
      oral corticosteroids are a difficult problem in therapeutics. OBJECTIVE: To
      investigate the relative efficacy of three treatment regimens of inhaled sodium
      cromoglycate in the treatment of adult, severe, corticosteroid-dependent patients
      as determined by the reduction in the dose of oral corticosteroids and change in
      lung function. METHODS: Open, randomized, group comparative trial of 12 weeks
      duration in asthmatic patients attending a hospital outpatient department.
      Patients whose asthma is (1) severe according to the classification of the
      Japanese Society of Allergology, (2) stable, and (3) needing treatment with at
      least 1600 microg of inhaled beclomethasone dipropionate and 5 mg or greater of
      oral prednisolone per day. The three treatment regimens of inhaled sodium
      cromoglycate were group A received sodium cromoglycate powder at a dose of 16
      mg/day administered by a metered dose inhaler. Group N received sodium
      cromoglycate aqueous solution at a dose of 80 mg/day administered by a nebulizer.
      Group C received sodium cromoglycate aqueous solution (80 mg/day) combined with
      salbutamol (3 mg/day) administered by a nebulizer. The main outcome measures were
      a change in the daily dose of oral corticosteroids and in lung function with
      twice daily measurements of peak expiratory flow (PEF) recorded in the morning
      (PEF AM) and in the evening (PEF PM). RESULTS: Mean reduction in oral
      corticosteroid dose/day was group A, 3.68 mg (95% CI 1.35,5.95); group N, 3.59 mg
      (95% CI 0.73,6.45); and group C, 3.97 mg (95% CI 1.81,6.13). The dosage
      reductions are all significant but with no differences between the groups. The
      mean increase in PEF over the last 4 weeks of treatment compared with baseline
      values was significant in all groups. The increases in group C are significantly
      greater than those in the other groups. These changes are all significant and the
      increases in group C are significantly greater than those in the other groups.
      CONCLUSIONS: Inhaled sodium cromoglycate may be a useful additional treatment in
      the management of adult patients with severe, oral steroid-dependent asthma. Of
      the three methods of administration compared in this trial the most useful
      immediate results were obtained when the drug was administered as an aqueous
      solution mixed with salbutamol and delivered by a powered nebulizer.

PMID- 9647274
TI  - Continuous nebulization therapy for asthma with aerosols of beta2 agonists.
AB  - BACKGROUND: Various studies have demonstrated the benefits of continuous
      nebulization therapy for delivering aerosols of the beta2 agonists such as
      terbutaline sulfate or albuterol sulfate to patients with severe asthma and/or
      impending respiratory failure. OBJECTIVE: The purpose of this investigation was
      to explicate the operational factors associated with the use of nebulizers for
      extended aerosol respiratory therapy including those factors that affect the
      prescribed aerosol dosages and the relationship to actual delivery of prescribed
      drugs to the respiratory airways of the lungs of a patient under treatment
      conditions. METHODS: Operational characteristics and methods have been
      investigated for use of long-running nebulizers for continuous nebulization
      therapy. Factors considered were particle size distribution, setup conditions,
      aerosolization concentrations and rates, delivery fraction of aerosol reaching
      patient, and changes in medication concentration during extended operation. With
      a large volume nebulizer, aerosols can be delivered to the patient without
      dilution via a standard open mask for up to eight hours without refill. The
      pneumatic HEART nebulizer with 240 mL reservoir was evaluated. RESULTS: The
      nebulizer was operated from a single compressed air or oxygen source and found to
      provide from 10 to 15 L/min of aerosol with 38 to 50 microL of aerosolized
      medicine per liter of air (or oxygen) and utilize from 30 to 56 mL/hour of
      medicinal liquid. The mass median aerodynamic diameter of the aerosol droplets
      was found to be about 2.0 microm (sigma(g) = 2.7). Delivery efficiency to the
      patient mask was about 90%. The aerosolized medicine delivered to the patient can
      be increased by adjusting the flow rate of the gas source or changing the
      solution concentration of medicine. Typically, several milligrams of drug can be
      delivered to the patient as inhaled aerosol per hour of treatment of which about
      one-quarter can be expected to be deposited in the lungs. During eight hours of
      operation the concentration of medicinal solution increased by about a factor of
      two because of water evaporation. CONCLUSIONS: Continuous nebulization therapy is
      an important means of treating patients with severe asthma. Dosage criteria can
      be established based on the operating characteristics of the nebulizer system,
      drug solution concentration, and patient respiration.

PMID- 9647275
TI  - Glucocorticoids inhibit proliferation and interleukin-4 and interleukin-5
      secretion by aeroallergen-specific T-helper type 2 cell lines.
AB  - BACKGROUND: Glucocorticoids play an important role in the treatment of allergic
      disease. The atopic process, itself, may reduce the response of peripheral blood
      mononuclear cells (PBMC) to these drugs. OBJECTIVE: In this study we compared the
      effect of hydrocortisone (HC), beclomethasone (BDP), and mometasone (MF) on
      interleukin (IL)-4 and IL-5 secretion by aeroallergen-specific T-helper type 2
      cells (Th2) and proliferation of PBMC from atopic donors. METHODS: Cells were
      incubated with drug before stimulating with phytohemagglutinin and assessing
      proliferation (PBMC) and cytokine secretion (Th2). RESULTS: The glucocorticoids
      concentration dependently inhibited proliferation and cytokine secretion, but had
      less effect on proliferation of cells from severe atopics than on cells from
      those whose symptoms required little treatment. The rank order of potency was MF
      (average IC50 0.01 nM) > BDP (4.0 nM) > HC (250 nM). CONCLUSIONS: These
      experiments demonstrate glucocorticoid inhibition of IL-4 and IL-5 secretion by
      human Th2-like cells and proliferation of PBMC from severely and mildly allergic
      donors.

PMID- 9647276
TI  - Developmental changes of unbound theophylline.

PMID- 9647277
TI  - Unenhanced and enhanced magnetic resonance imaging in the diagnosis of multiple
      sclerosis.
AB  - Initial enthusiasm about the role of magnetic resonance imaging (MRI) in the
      diagnosis of multiple sclerosis decreased substantially with the notion that (a)
      lesions of various pathological origins may resemble demyelinating plaques and
      (b) a dissemination of lesions throughout the brain is not unique for multiple
      sclerosis but may even be a "normal" finding. Current experience still does not
      allow the identification of the aetiology of a single hyperintensity but has
      identified multiple features of multiple sclerosis related signal abnormalities
      which, in combination, provide rather high diagnostic accuracy. Useful
      characteristics include the distribution of lesions such as a strictly
      periventricular, infratentorial or juxtacortical location, and involvement of the
      corpus callosum. The presence of contrast enhancement in some but not all lesions
      that is, evidence of both old and new lesions-provides additional diagnostic
      support. Improved instrumentation for imaging of the spine further extends the
      diagnostic options. Intramedullary signal abnormalities are detected with
      increased sensitivity and may disclose the presence of multiple lesions even in
      patients with an equivocal or a negative MRI of the brain. The high sensitivity
      to plaques and the opportunity to simultaneously rule out other gross
      morphological damage justifies the use of MRI as the primary diagnostic modality
      in the evaluation of multiple sclerosis.

PMID- 9647278
TI  - Differential diagnosis of multiple sclerosis: contribution of magnetic resonance
      techniques.
AB  - It is widely accepted that magnetic resonance imaging (MRI) findings are not
      totally specific for the diagnosis of multiple sclerosis. White matter lesions
      that mimic those of multiple sclerosis may be detected in both normal volunteers
      and patients harbouring different diseases. Virtually all the characteristic
      features of multiple sclerosis are sometimes encountered in other conditions
      affecting predominantly the white matter. Different conditions such as
      vasculitis, subcortical atherosclerotic leukoencephalopathy, Lyme disease, or
      acute disseminated encephalomyelitis can be virtually indistinguishable from
      multiple sclerosis on conventional MR images. Also the FLAIR technique adds
      little to the differential diagnosis. The calculation of magnetisation transfer
      ratio (MT ratio) may be useful to better characterise some entities, such as
      vasculitis, from multiple sclerosis.

PMID- 9647279
TI  - The contribution of magnetic resonance imaging to the assessment of optic nerve
      and spinal cord involvement in multiple sclerosis.
AB  - Magnetic resonance imaging of the optic nerve and spinal cord in multiple
      sclerosis has advanced considerably in the past decade. It is possible to
      reliably detect intrinsic optic nerve and spinal cord lesions due to
      demyelinating disease. Detection of these can assist diagnosis, especially in the
      spinal cord. As demyelinating lesions in these structures are often symptomatic,
      MR imaging in these regions also provides a special opportunity to obtain
      insights into pathophysiological and pathogenetic mechanisms.

PMID- 9647280
TI  - Clinical, neurophysiological, and magnetic resonance imaging correlations in
      multiple sclerosis.
AB  - Magnetic resonance imaging (MRI) has a pivotal role in diagnosis of multiple
      sclerosis and is being increasingly used as a paraclinical measure to assess
      treatment efficacy in clinical trials. However, the correlations between clinical
      and MRI findings in patients with multiple sclerosis are weak and, therefore,
      newer MR techniques are being developed to increase both MRI sensitivity for
      detecting disease activity and its pathological specificity for better assessing
      disease evolution. Evoked potentials (EPs) can be used to confirm the diagnosis
      of multiple sclerosis and their abnormalities are correlated with symptoms and
      signs referable to involvement of the corresponding nervous pathways. However,
      their use is limited when assessing disease progression and monitoring clinical
      trials in multiple sclerosis. Both magnetic resonance imaging (MRI) and evoked
      potentials (EPs) provide information which cannot be obtained by clinical
      evaluation, especially for assessing disease activity. Nevertheless, both these
      paraclinical techniques cannot substitute for clinical measures of disability
      when assessing disease progression and monitoring phase III clinical trials in
      multiple sclerosis.

PMID- 9647281
TI  - The lesion in multiple sclerosis: clinical, pathological, and magnetic resonance
      imaging considerations.
AB  - Despite the cause of multiple sclerosis remaining elusive, recent studies of the
      disease using magnetic resonance imaging (MRI) and detailed pathological analysis
      have provided new insights into the events involved in the evolution of the
      lesion in multiple sclerosis. Most evidence points to disruption of the blood
      brain barrier as the initial event in development of the lesion in multiple
      sclerosis. It is thought that antigen specific T cells enter the nervous system,
      recognise antigen, and begin a cytokine cascade that mediates disruption of the
      blood-brain barrier seen on contrast enhanced MRI. Subsequently, the inflammatory
      response is amplified and the effector stage leading to myelin damage is
      initiated. The mechanism(s) causing myelin damage is uncertain. MRI and
      pathological studies now indicate that damage to the axon may occur earlier in
      lesion development than generally thought. Although T2 weighted MRI techniques
      lack pathological specificity, considerable attention is now focused on studying
      newer techniques that should provide greater insight into lesion development.
      These include studies of hypointensities on T1 weighted images, proton
      spectroscopy, magnetisation transfer imaging, and diffusion imaging. Hopefully,
      these new techniques will provide a better understanding of events involved in
      the multiple sclerosis lesion as well as an improved understanding of the
      relation between disease as measured on MRI and that seen clinically.

PMID- 9647282
TI  - Correlating immunological and magnetic resonance imaging markers of disease
      activity in multiple sclerosis.
AB  - Inflammation plays a central part in the pathogenesis of multiple sclerosis.
      However, current surrogate magnetic resonance (MR) and immunological markers of
      inflammation are weakly associated and correlate poorly with clinical
      progression. Reasons for this are multiple and probably relate to the non
      specific changes and insensitivity of current MR techniques, disease dynamics,
      anatomical factors, and the temporal profile and poorly defined complexities of
      the inflammatory reaction in multiple sclerosis. This paper provides an overview
      of the principles involved in the monitoring of inflammation in multiple
      sclerosis, discusses possible reasons for the weak correlation between MR and
      immunological markers of inflammation, and briefly reviews the studies
      correlating these modalities. In addition, the predictive values of MRI and CSF
      oligoclonal immunoglobulin are compared in determining future progression to
      clinically definite multiple sclerosis in patients presenting with clinically
      isolated syndromes compatible with demyelination.

PMID- 9647283
TI  - Standardisation and optimisation of magnetic resonance techniques for multicentre
      studies.
AB  - AIM: An approach to measuring physical quantities such as lesion load with MRI in
      multicentre studies is presented. METHOD: Examples are given of imperfections in
      current techniques: (1) a step change in a serial trial, giving an apparent (but
      artefactual) decrease in total lesion volume in untreated patients with multiple
      sclerosis; (2) inaccuracy (systematic error) in lesion volume, found by measuring
      a phantom with lesions of known volumes; (3) spatial non-uniformity in the
      radiofrequency coil sensitivity, giving gross image shading. When using the
      magnetic resonance imaging (MRI) scanner as a scientific instrument to measure
      physical quantities, accuracy (closeness to the truth, or lack of systematic
      error), and precision (reproducibility, or lack of random error) are the keys to
      success. Quality assurance procedures can utilise phantoms, normal control
      subjects, and stable patients, and have to be included in serial studies and
      trials. Between scanner agreement can perhaps be improved by attempting to
      replicate an inaccurate procedure at each site; but it is more preferable to seek
      accuracy and precision (as a perfectly accurate and precise procedure must give
      the same results at all sites). CONCLUSION: Before being included in a serial
      study, a measurement procedure should ideally demonstrate:(1) accuracy in a
      phantom; (2) precision in repeated measurements on a phantom; (3) precision in
      repeated measurements on human subjects.

PMID- 9647284
TI  - Magnetic resonance imaging techniques to monitor short term evolution of multiple
      sclerosis and to use in preliminary trials.
AB  - Short term serial magnetic resonance imaging (MRI) studies have provided major
      new insights into the natural history of multiple sclerosis, and are providing an
      excellent tool for preliminary assessment of therapeutic effect. In early
      relapsing-remitting and secondary progressive multiple sclerosis, monthly T2
      weighted and gadolinium enhanced scanning discloses, on average, about 10 new or
      enhancing lesions for each clinical relapse. This approach relies largely on the
      detection of acute inflammatory MRI activity with blood-brain barrier break down-
      as the importance of this for long term disability remains uncertain, these
      methods for the present should not be used as the definitive assessment of
      treatment outcome.

PMID- 9647285
TI  - Magnetic resonance techniques to monitor the long term evolution of multiple
      sclerosis pathology and to monitor definitive clinical trials.
AB  - Magnetic resonance has provided a literal window on the brain to visualise the
      actual pathology of MS as it evolves in the living patient. Natural history
      studies disclosed that MRI visualised pathological activity was seen at 5 to 10x
      the rate of clinical relapses. Utilising that knowledge, systematic MRI
      monitoring has been used to supplement clinical monitoring to show the treatment
      effect in several clinical trials. This chapter explains how MR techniques can be
      used to further explore the evolution of in vivo pathology both in clinical
      trials and natural history studies.

PMID- 9647286
TI  - The role of non-conventional magnetic resonance techniques in monitoring
      evolution of multiple sclerosis.
AB  - Conventional magnetic resonance imaging (MRI) techniques have proved to be
      extremely useful to monitor multiple sclerosis activity and evolution. The recent
      development and clinical application of non-conventional MR techniques has the
      potential to further increase the importance of MR in the evaluation of multiple
      sclerosis by reducing the time needed for acquisition of the data, by improving
      sensitivity, and by increasing the pathological specificity of the abnormalities
      detected. In the present review, the main results obtained using these newer
      techniques in the study of the natural history of the disease and the future
      possible applications in clinical trials are presented.

PMID- 9647287
TI  - The role of techniques characterised by faster acquisition times in the
      evaluation of multiple sclerosis.
AB  - Magnetic resonance imaging (MRI) methods with shorter acquisition times are
      considered. Fast spin echo sequences allow faster scanning with images comparable
      with conventional spin echo. Fast fluid attenuated inversion recovery (fast
      FLAIR) may provide a more complete picture of multiple sclerosis evolution, but
      more validation studies are still needed. Faster imaging methods, such as
      turbogradient spin echo and echo planar imaging, have marked advantages for
      uncooperative patients for diagnostic purposes and reduced motion related
      artifacts but may involve sacrifices of signal to noise, contrast, spatial
      resolution, and image quality. All methods are useful for clinical diagnosis,
      with fast spin echo generally accepted as equivalent to conventional spin echo.
      For quantitative evaluation in multiple sclerosis, further work is needed to
      define the utility of the faster and ultrafast methods.

PMID- 9647288
TI  - Magnetisation transfer imaging: theory and application to multiple sclerosis.
AB  - Magnetic resonance imaging techniques based on magnetisation transfer exploit the
      inherent heterogeneity of tissue with respect to relaxation times T1 and T2.
      Contrast reflecting the interactions between distinct relaxation "environments"
      may be exploited via novel quantitative analysis for potential gains in
      specificity of the MR examination in multiple sclerosis.

PMID- 9647289
TI  - Nuclear magnetic resonance relaxation in multiple sclerosis.
AB  - OBJECTIVES: The theory of relaxation processes and their measurements are
      described. An overview is presented of the literature on relaxation time
      measurements in the normal and the developing brain, in experimental diseases in
      animals, and in patients with multiple sclerosis. RESULTS AND CONCLUSION:
      Relaxation time measurements provide insight into development of multiple
      sclerosis plaques, especially the occurrence of oedema, demyelination, and
      gliosis. There is also evidence that normal appearing white matter in patients
      with multiple sclerosis is affected. What is now needed are fast and accurate
      relaxation time measurement procedures, which cover the whole brain. Relaxation
      time measurements could then provide an important tool for studying the
      pathogenesis of demyelinating diseases and thus be useful in follow up studies.

PMID- 9647290
TI  - Hypointense multiple sclerosis lesions on T1-weighted spin echo magnetic
      resonance images: their contribution in understanding multiple sclerosis
      evolution.
AB  - The predictive value of T2-weighted imaging in multiple sclerosis is only
      moderate, due to low specificity of high signal on such images. Among new MR
      techniques with acclaimed higher pathological specificity, hypointense lesions on
      moderately T1-weighted spin echo images show improved correlation with
      disability. The degree of hypointensity of so called black holes correlates with
      loss of magnetisation transfer, a marker of matrix destruction. Severe tissue
      loss is also shown histopathologically in a post-mortem MR study of black holes.
      In this review unresolved issues regarding black holes are discussed including
      standardisation of sequences, definition of hypointensity, interobserver
      variation in measuring lesion load with this technique, and significance of acute
      black holes. The role of black holes in monitoring treatment efficacy is as yet
      unexplored.

PMID- 9647291
TI  - Diffusion magnetic resonance imaging in multiple sclerosis.
AB  - This paper reviews the use of magnetic resonance diffusion imaging in studies of
      multiple sclerosis. Firstly, the principles of diffusion imaging are explained
      together with a discussion of the hardware and techniques required. The concept
      of diffusion tensor imaging is introduced and images obtained using this method
      are presented. Studies that have used diffusion imaging in patients with multiple
      sclerosis and the implications of the results are discussed. There is an increase
      in the diffusion coefficient of water molecules in the plaques of patients with
      multiple sclerosis, compared with healthy brain. Some workers also report
      increased diffusion in the normal appearing white matter of some patients with
      multiple sclerosis. Possible mechanisms are given for these findings, together
      with the experimental evidence to support them.

PMID- 9647292
TI  - Functional magnetic resonance imaging in multiple sclerosis.
AB  - Functional magnetic resonance imaging (fMRI) is a method that combines high
      anatomical spatial resolution with the ability to localise function. Visual and
      motor systems are among those that have received most attention. Yet the clinical
      application is still limited. Recently, some investigators applied fMRI to study
      patients with multiple sclerosis. Patients with partial motor weakness disclosed
      a larger area of cortical activation bilaterally by contrast with healthy
      volunteers when using the affected arm, whereas patients with optical neuritis
      disclosed a smaller area of activation, when stimulating the affected eye. These
      results show that different systems might react heterogeneously.

PMID- 9647293
TI  - Quantitative assessment of magnetic resonance imaging lesion load in multiple
      sclerosis.
AB  - Changes of lesion load on yearly conventional spin echo (CSE) T2-weighted scans
      of the brain from patients with multiple sclerosis, measured using computer
      assisted techniques, are used to monitor long term disease evolution, either
      natural or modified by treatment. Although lesion load measurements have several
      advantages over clinical measures of outcome (they provide a more objective and
      sensitive measure of disease evolution, which has a linear distribution and a
      more strict relation with the underlying pathology), the poor correlation between
      changes of lesion load and changes of disability is of concern when using such an
      approach for monitoring multiple sclerosis trials. In this review, the main
      sources of variation in T2 lesion load from brain MRI of patients with multiple
      sclerosis will be considered, along with possible strategies to, at least
      partially, overcome them. Also, some of the newer fully automated techniques to
      segment multiple sclerosis lesions, which have been validated against manual
      outlining, and a recently developed coregistration technique are presented. It is
      hoped that a more reliable and standardised approach to lesion load measurements
      in multiple sclerosis will lead to better correlation with clinical disease
      course, to a higher confidence in the results of trials, and to reduced numbers
      of scans needed to conduct the trials, thus improving cost efficiency and
      reducing discomfort of the patients.

PMID- 9647294
TI  - The use of magnetic resonance spectroscopy in the evaluation of the natural
      history of multiple sclerosis.
AB  - Magnetic resonance spectroscopic imaging (MRSI) can be used to define specific
      chemical-pathological changes in the brain of patients with multiple sclerosis.
      Magnetic resonance spectroscopy offers promise for improved definition of the
      nature of individual lesions, the dynamics of their evolution, their effects on
      normal appearing white matter, and their relation to clinical disability.
      Combined multimodal MRSI studies of the brains of patients with multiple
      sclerosis therefore soon may provide efficient, specific, and quantitative new
      approaches to assessment of drug effects in therapeutic trials.

PMID- 9647295
TI  - Measures of brain and spinal cord atrophy in multiple sclerosis.
AB  - Although conventional magnetic resonance imaging (MRI) has greatly increased the
      understanding of the pathophysiology of multiple sclerosis, its relation to the
      development of disability is complex. More pathologically specific imaging
      markers have therefore been sought to try and understand the underlying process
      that is responsible for the progressive disability that so commonly occurs in
      multiple sclerosis. Of these the most simple to understand conceptually is the
      measurement of atrophy, which most probably represents axonal loss. Several
      recent studies have shown that atrophy is a process closely linked with the
      progressive phase of multiple sclerosis and worsening disability. Furthermore it
      has also been shown that atrophy may evolve despite the absence of inflammatory
      activity as judged by gadolinium enhanced MRI and thus its measurement gives
      information in addition to that obtained from conventional MRI. Because of new
      developments in imaging we are now able to measure atrophy reliably and
      reproducibly. Hence the measurement of atrophy now provides objective markers by
      which to evaluate putative treatment aimed at preventing disability in multiple
      sclerosis.

PMID- 9647296
TI  - Alzheimer's disease, amyotrophic lateral sclerosis, and transgenic mice.

PMID- 9647297
TI  - Prevention of strokes and recurrent strokes.

PMID- 9647298
TI  - The neurology of pregnancy.

PMID- 9647299
TI  - "Summary measure" statistic for assessing the outcome of treatment trials in
      relapsing-remitting multiple sclerosis.
AB  - OBJECTIVES: To review the outcome measures commonly used in phase III treatment
      trials of relapsing-remitting multiple sclerosis and to introduce a method of
      data analysis which is clinically appropriate for the often reversible disability
      in this type of multiple sclerosis. METHODS: The conventional end point measures
      for disability change are inadequate and potentially misleading. Those using the
      disability difference between study entry and completion do not take into account
      serial data or disease fluctuations. Rigid definitions of "disease progression"
      based on two measurements of change in disability several months apart, do not
      assess worsening after the defined "end point", nor the significant proportion of
      erroneous "treatment failures" which result from subsequent recovery from
      relapses that outlast the end point. Assessing attacks merely by counting their
      frequency ignores the variation in magnitude and duration. These problems can be
      largely circumvented by integrating the area under a disability-time curve (AUC),
      a technique which utilises all serial measurements at scheduled visits and during
      relapses to summarise the total neurological dysfunction experienced by an
      individual patient on any particular clinical scale during a study period.
      CONCLUSIONS: The "summary measure" statistic AUC incorporates both transient and
      progressive disability into an overall estimate of the dysfunction that was
      experienced by a patient during a period of time. It is statistically more
      powerful and clinically more meaningful than conventional methods of assessing
      disability changes, particularly for trials which are too short to expect to
      disclose major treatment effects on irreversible disability in patients with a
      fluctuating disease.

PMID- 9647300
TI  - High incidence and prevalence of multiple sclerosis in south east Scotland:
      evidence of a genetic predisposition.
AB  - OBJECTIVE: To determine the incidence and prevalence of multiple sclerosis in the
      Lothian and Border Health Board Regions of south east Scotland. METHODS:
      Incidence study: all patients were identified in whom a diagnosis of Poser
      category probable or definite multiple sclerosis was made by a neurologist
      between 1992 and 1995. Prevalence study: all patients known to have multiple
      sclerosis who were alive and resident in the study area on 15 March 1995 were
      recorded. RESULTS: The crude annual incidence rates of probable or definite
      multiple sclerosis per 100000 population were the highest ever reported: 12.2
      (95% confidence interval (95% CI) 10.8-13.7) in the Lothian Region and 10.1 (95%
      CI 6.6-13.6) in the Border Region. A total of 1613 patients with multiple
      sclerosis were resident in the study area, giving standardised prevalence rates
      per 100000 population of 203 (95% CI 192-214) in the Lothian Region and 219 (95%
      CI 191-251) in the Border Region. Prevalent cases were more likely than expected
      to have a Scottish surname (risk ratio 1.24, 95% CI 1.14-1.34). CONCLUSION:
      Orkney and Shetland were previously thought to have by far the highest prevalence
      of multiple sclerosis in the world: about double that found in England and Wales.
      However, the prevalence in south east Scotland is equally high, suggesting that
      the Scottish population as a whole has a genetic susceptibility to the disease,
      and undermining the hypothesis that patterns of infection specific to small
      sparsely populated island communities are important in the causation of multiple
      sclerosis.

PMID- 9647301
TI  - Clinical relapses and disease activity on magnetic resonance imaging associated
      with viral upper respiratory tract infections in multiple sclerosis.
AB  - BACKGROUND: Although the risk of clinical attacks of multiple sclerosis seems to
      be significantly increased with viral upper respiratory tract infections (URTI),
      serological evidence for the reported association remains controversial. In
      addition, although MRI is six to 10 times more sensitive than clinical
      exacerbations in indexing disease activity, any possible association between URTI
      and MRI activity has yet to be investigated. OBJECTIVES: To examine the relation
      between URTI and disease activity, in multiple sclerosis patients participating
      in a placebo controlled trial of interferon beta-1a, as indexed both by clinical
      exacerbation rate and by the number and volume of gadolinium
      diethylenetriaminepentaacetic acid (Gd-DTPA) enhancing lesions on MRI. "At risk"
      periods were defined around symptomatic URTI, with or without serological
      confirmation. RESULTS: The relative risk of clinical relapse for serologically
      unconfirmed symptomatic URTI was 2.1 (p=0.004). Raised antiviral antibody titres
      conferred a relative risk of multiple sclerosis exacerbations that was 3.4 times
      higher than the "not at risk" periods (annual attack rates of 5.7 v 1.6,
      respectively, p=0.006). There was no definite relation between the number or the
      volume of active lesions on MRI and either symptomatic or serologically defined
      at risk periods. CONCLUSIONS: These results confirm the previously reported
      association between viral infections and multiple sclerosis exacerbations and
      indicate that the relative risk may be even higher when viral infection is
      serologically confirmed. However, the results, perhaps because of the confounding
      effects of interferon beta-1a, do not provide convincing evidence of increased
      blood-brain barrier breakdown or inflammation during periods of virally induced
      immune stimulation.

PMID- 9647302
TI  - Longitudinal SPECT study in Alzheimer's disease: relation to apolipoprotein E
      polymorphism.
AB  - OBJECTIVES: In mild Alzheimer's disease, SPECT imaging of regional cerebral blood
      flow has highlighted deficits in the posterior association cortex, and later in
      the disease process, the deficit spreads to involve the frontal cortex. The
      sigma4 allele of apolipoprotein E is a risk factor for Alzheimer's disease. The
      effect of apolipoprotein E polymorphism on cerebral perfusion was studied. The
      hypothesis was that those patients with Alzheimer's disease who carry the sigma4
      allele would have more severe cerebral hypoperfusion. METHODS: Thirty one
      patients with Alzheimer's disease and eight age and sex matched control subjects
      were examined in a three year longitudinal study. Patients with Alzheimer's
      disease were divided into subgroups according to their number of sigma4 alleles.
      Regional cerebral blood flow ratios referred to the cerebellum were examined by
      99mTc-HMPAO SPECT. Apolipoprotein E genotypes were determined by digestion of
      polymerase chain reaction products with the restriction enzyme Hha1. RESULTS: All
      patients with Alzheimer's disease had bilateral temporoparietal hypoperfusion
      compared with control subjects. The two sigma4 allele subgroups had the lowest
      ratios at the baseline assessment in the parietal and occipital cortices, and at
      the follow up in the temporal, parietal, and occipital cortices. They had the
      highest reduction in percentage terms in the temporal and occipital cortices
      compared with the other subgroups. However, the global clinical severity did not
      differ at the baseline or follow up examinations between the subgroups.
      CONCLUSION: Apolipoprotein E polymorphism is involved in the pathogenesis and
      heterogeneity of Alzheimer's disease as the most severe cerebral hypoperfusion
      was found in the sigma4 allele subgroups. This might have implications for
      therapeutic approaches in Alzheimer's disease.

PMID- 9647303
TI  - Application of the MRC brain tumour prognostic index to patients with malignant
      glioma not managed in randomised control trial.
AB  - OBJECTIVES: The MRC brain tumour prognostic index, which uses clinical variables
      to place patients in different outcome categories, has not been evaluated on a
      cohort outside a randomised controlled trial. The aims of this study were to (a)
      determine in a large cohort of patients, derived solely from one centre and not
      in a clinical trial, whether the MRC prognostic index stratified patients for
      outcome; (b) compare actual outcomes with those obtained in the original studies;
      and (c) examine whether neuropathological diagnosis was an independent prognostic
      variable. METHODS: The MRC prognostic index was calculated for 236 patients with
      either glioblastoma or anaplastic astrocytoma managed at a dedicated neuro
      oncology clinic in Edinburgh between 1989 and 1995. RESULTS: For this mixed
      population of malignant glioma the median survival was 8.6 months. Two year
      survival was 72.2% for patients with an MRC index score of 1-10; 36.3% for those
      with an index score of 11-15; 25.1% for those scoring 16-20; 20.4% with those
      scoring 21-25; 4.8% with those scoring 26-33; and 0% for those scoring 34-38.
      Exclusion of 79 patients who would not have been eligible for the MRC studies
      from which the index was derived, because they were either too old or did not
      receive radiotherapy, still resulted in a similar pattern of stratification but
      with significantly improved median survival times for the lowest two categories.
      Multivariate analysis of prognostic variables in the Edinburgh cohort showed that
      patients with anaplastic astrocytoma did significantly better than those with
      glioblastoma (p<0.001). CONCLUSIONS: Although there were some differences in
      median survival times between the patients in the original MRC studies and the
      Edinburgh cohort in similar prognostic categories and a tendency to improved two
      year survivorship in the Edinburgh cohort these differences have arisen because
      (a) the Edinburgh cohort was accrued about 10 years later than the study has
      shown that even outside the setting of a prospective controlled trial and with
      relaxed inclusion criteria the Medical Research Council (MRC) prognostic index is
      a robust predictor of outcome in patients with malignant glioma. Survival clearly
      declines as the prognostic index increases. Moreover, the prognostic model can be
      substantially improved by the addition of histology data, although there is some
      evidence that this will require complex modelling procedures.

PMID- 9647304
TI  - Long term results of botulinum toxin type A (Dysport) in the treatment of
      hemifacial spasm: a report of 175 cases.
AB  - OBJECTIVE: To describe the long term efficacy and side effects of the treatment
      of hemifacial spasm with Dysport and to evaluate two different sites of injection
      to hopefully reduce side effects. METHODS: This study was designed as a
      prospective descriptive study. Injections were made subcutaneously around the
      eye. Peak improvement was subjectively assessed by using a visual analogue scale
      and reported in percentages (0-100%). Duration of improvement was assessed
      subjectively and reported in months. RESULTS: Of 175 cases, 17 were lost to
      follow up and were excluded. 855 treatments were injected in the remaining 158
      patients with a median of 4 treatments. The response rate was 97%. Of 855
      treatments, the adjusted mean peak and duration of improvement was 77.2 (95%
      confidence interval (95%CI) 74.7-79.4)% and 3.4 (95%CI 3.2-3.6) months
      respectively. In 158 patients (complete group), the long term results from the
      first to the 12th treatment showed that the mean peak improvement ranged from
      72.70 to 80.10% and the duration of improvement was 2.60 to 3.71 months. It
      remained constant throughout (p=0.40, p=0.87 respectively). The most common side
      effect was ptosis. Of the 158 patients, 21 completed 12 treatments (subgroup). A
      separate analysis of this group disclosed a mean peak and duration of improvement
      from the first to 12th treatments ranging from 70.00 to 78.10% and 2.65 to 4.31
      months respectively. Analysis of variance with repeated measures showed no
      significant variation of peak and duration of improvement over the first to the
      12th treatments (p=0.38, p=0.38 respectively). Only 3% of the treatments were
      unsuccessful but responded to subsequent treatments. The incidence of ptosis was
      reduced from 27.17% to 9.68% by moving the injection site to the lateral part of
      orbital orbicularis oculi without any loss of efficacy. The yearly cost of
      Dysport is considerably less than Botox. CONCLUSION: This study is the first to
      show, in detail, the long term results of treatments of hemifacial spasm with
      Dysport. The efficacy is constant throughout orbicularis oculi. The efficacy of
      Dysport is comparable with Botox in long term follow up.

PMID- 9647305
TI  - Genetic polymorphisms adjacent to the CAG repeat influence clinical features at
      onset in Huntington's disease.
AB  - OBJECTIVES: To evaluate possible influences of CCG and delta2642 glutamic acid
      polymorphisms adjacent to the (CAG)n trinucleotide repeat in Huntington's disease
      gene IT15 on some clinical features (age and symptoms) at onset. METHODS: 84
      patients and a control group of 68 unaffected relatives were studied. Patients
      all belonged to a group of affected persons tested for molecular confirmation of
      Huntington's disease. The length of the CAG repeat sequence in the IT15 gene and
      the adjacent CCG and delta2642 polymorphisms were determined by quantitative
      polymerase chain reaction. RESULTS: Two intragenic polymorphisms were studied:
      (CCG)n and delta2642 glutamic acid. Patients were classified firstly according to
      the size of the CCG rich segment adjacent to the CAG repeat into genotype groups
      CCG 7/7, 7/8, 7/9, 7/10, and 10/10 and then according to delta2642 polymorphism
      into genotype groups A/A (absence of the delta2642 deletion), A/B, and B/B
      (presence of the delta2642 deletion in respectively one and two alleles). The
      presence of delta2642 mutation was associated with a significant decrease in age
      at onset, although there was no significant increase in CAG size. A good
      correlation was found between the (CAG)n trinucleotide repeat size and the age at
      onset in patients with genotype AA (r2=0.72). Within patients of the A/B genotype
      group however, a significant correlation was found but with a drop of the r2
      value to 0.44. No association was found between age at onset and the CCG
      polymorphism. Although an increased percentage of patients within the A/A
      genotype group had a neurological onset, we found no overall significant
      association between CCG or delta2642 polymorphisms and the nature of symptoms at
      onset. CONCLUSIONS: The delta2642 glutamic acid polymorphism did not affect CAG
      repeat size nor the nature of symptoms at onset but seems to influence the age at
      onset in patients with Huntington's disease.

PMID- 9647307
TI  - Post-traumatic cerebral venous sinus air embolism.

PMID- 9647306
TI  - Lightning stroke and neuropsychological impairment: cases and questions.
AB  - OBJECTIVE: To objectify neuropsychological impairments in survivors of lightning
      stroke with lasting complaints about poor concentration and inability to divide
      their attention. DESIGN: A series of six cases of lightning stroke were studied.
      All patients had lost consciousness and reported amnesia of varying length.
      Assessment took place between one and four years after injury, ensuring that
      their neurological state had stabilised. They were tested with a
      neuropsychological battery with an emphasis on attention and memory. Personality
      and emotional reaction to the accident were assessed with questionnaires and a
      lightning fear scale. Complaints were recorded by means of a trauma complaints
      list including 10 questions on symptoms of the post-traumatic stress disorder.
      RESULTS: Patients reported fatigue and lack of energy as their main complaints.
      In addition, poor concentration, irritability, and emotional lability were
      mentioned often. Neuropsychological tests disclosed mild impairments in memory,
      attention, and visual reaction times. Two patients could be classified as
      depressed, and one of these also showed convincing signs of the post-traumatic
      stress disorder. CONCLUSION: As the lasting complaints and impairments could not
      be explained, for all six cases, as resulting from head injury concomitant with
      lightning stroke, cerebral hypoxia or a post-traumatic stress syndrome, it is
      concluded that lightning stroke can result in subtle cognitive impairments. It is
      speculated that most complaints of these survivors are caused by a vegetative
      dysregulation, a disorder that has often been noted in the literature on the
      effects of electrical injury to the nervous system. Such a dysregulation might
      cause both the main complaint of fatigue and the mild cognitive impairments
      identified with the present test battery.

PMID- 9647308
TI  - Mechanisms of second and further strokes.
AB  - OBJECTIVES: The mechanisms underlying recurrent stroke may be complex and
      multifactorial, but they have not been studied systematically. The aim was to
      analyse the different patterns and pathophysiological mechanisms of second and
      further strokes. METHODS: Recurrent stroke patterns and mechanisms were studied
      in 102 patients admitted with second or further strokes to the stroke centre in
      Lausanne University Hospital. RESULTS: The patients with an initial cardioembolic
      stroke experienced recurrent stroke of the same type most often, followed by
      those with initial non-lacunar non-cardioembolic stroke, brain haemorrhage, and
      lacunar stroke (77%, 65%, 58%, and 48% respectively). Forty two per cent of the
      recurrent strokes in patients with an initial brain haemorrhage were ischaemic,
      whereas patients with ischaemic stroke only occasionally suffered brain
      haemorrhage (5%). In patients with brain haemorrhage, the lobar location
      predominated in both the first and all episodes (69% and 78% respectively),
      suggesting a small, occult arteriovenous malformation or cerebral amyloid
      angiopathy rather than hypertensive small artery disease. The functional
      disability of patients after an initial lacunar stroke was significantly better
      than in patients with other stroke subtypes (p<0.001), but the difference became
      non-significant after recurrent stroke (p=0.26). CONCLUSIONS: Most of the
      recurrent strokes were of the same type as the first episode for both
      cardioembolic and non-lacunar non-cardioembolic stroke, however, about half of
      the patients with an initial brain haemorrhage or a lacunar stroke experienced
      other types of stroke recurrently. The findings suggest that the coexistence of
      multiple aetiologies may play a major part in determining the mechanism of stroke
      recurrence. The study is an important step in understanding the patterns of
      stroke recurrence, which may be critical for better prevention.

PMID- 9647309
TI  - Auditory evoked neuromagnetic response in cerebrovascular diseases: a preliminary
      study.
AB  - OBJECTIVES: Magnetoencephalography (MEG) measures aspects of the function of the
      auditory cortex of the human brain with high spatial resolution. The objective
      was to determine whether MEG also accurately identifies the auditory cortex of
      the brain in patients with ischaemic stroke. METHODS: The auditory evoked
      magnetic field (AEF) was examined after stimuli of 1 kHz tone bursts in 24 stroke
      patients without apparent infarcts in the auditory cortex, and compared the
      topography of sources of 50 ms (P50m) and 100 ms latency deflections (N100m), the
      most prominent components of middle and long latency AEFs, with that of 12 normal
      subjects. Cerebral haemodynamics in and around the auditory cortex were evaluated
      using PET. RESULTS: In nine of 24 stroke patients, the accurate magnetic sources
      of P50m or N100m were not identified. The distribution of P50m sources varied
      more widely than N100m. Eight of these nine patients had severe stenotic lesions
      in the carotid or middle cerebral arterial trunks. Patients with abnormal P50m
      responses had decreased supratemporal and hemispheric blood flow compared with
      patients with normal P50m responses. CONCLUSIONS: These findings suggest that
      large vessel disease with disturbed cerebral haemodynamics in and near the
      auditory cortex tend to affect AEFs, especially the middle latency components.
      This is the first combined study of MEG and PET to show a significant correlation
      between AEF responses in stroke patients and their PET indices.

PMID- 9647310
TI  - Diabetic neuropathic cachexia: report of a recurrent case.
AB  - Diabetic neuropathic cachexia is an uncommon peripheral neuropathy associated
      with diabetes mellitus and characterised by profound weight loss and painful
      dysaesthesias over the limbs and trunk. The pathophysiological basis of this
      disorder remains unknown and there have been no published cases of recurrent
      episodes. A hispanic man who experienced two episodes of diabetic neuropathic
      cachexia over a seven year period is described.

PMID- 9647311
TI  - Hermann von Helmholtz (1821-94)

PMID- 9647312
TI  - An unusual course of progressive multifocal leukoencephalopathy in a patient with
      idiopathic CD4+ T lymphocytopenia.
AB  - A case is reported of idiopathic CD4+T lymphocytopenia with progressive
      multifocal leukoencephalopathy and cervical lymph node tuberculosis. A 57 year
      old Japanese man presented with cervical lymphadenopathy and progressive
      neurological deficits, and six months later he developed akinetic mutism. He had
      a persistent severely depressed number of circulating CD4+T lymphocytes in the
      absence of human immunodeficiency virus infection. T1 weighted MRI showed a
      diffuse decreased signal intensity limited to the white matter without mass
      effect. A brain biopsy specimen had a morphology similar to that of progressive
      multifocal leukoencephalopathy. Polyomavirus antigen was detected in the brain
      lesion, and viral DNA was identified in nucleated blood cells and urine.
      Unusually this serious medical condition has lasted for more than three years
      without remission. To our knowledge this is the first patient with CD4+T
      lymphocytopenia with progressive multifocal leukoencephalopathy, suggesting that
      similar opportunistic infections should be considered even in previously normal
      people.

PMID- 9647313
TI  - Intracerebral temperature in patients with hydrocephalus of varying aetiology.
AB  - Brain temperature was measured at various depths beneath the pial surface in
      patients with hydrocephalus of varying aetiology. Temperature increased gradually
      with depth in all patients, with the highest temperature found in the ventricle.
      The difference between intraventricular and rectal temperatures (delta v-r) was
      greater in patients who underwent continuous ventricular drainage than in
      patients who underwent ventriculoperitoneal shunt (continuous ventricular
      drainage; 1.2 (SD 0.40) degrees C, mean (SD), n=5 v ventriculoperitoneal shunt;
      0.4 (SD 0.45) degrees C, n=16; p< 0.05). The difference between intracerebral and
      rectal temperatures (delta b2-r) was also greater in patients with continuous
      ventricular drainage than in patients with ventriculoperitoneal shunt (continuous
      ventricular drainage; 0.1 (SD 0.86) degrees C, n=5 v ventriculoperitoneal shunt; 
      0.7 (0.86) degrees C, n=16; p< 0.05). Among patients with normal pressure
      hydrocephalus, these differences were greater in the patients with better
      outcomes after shunt surgery than in the less improved group (delta v-r; 0.7 (SD
      0.27) degrees C, n=7 v 0.1 (SD 0.40) degrees C, n=5, p< 0.01, delta b2-r; -0.2
      (SD 0.61) degrees C, n=7 v -1.4 (0.90) degrees C, n=5, p< 0.01).

PMID- 9647314
TI  - The selective inability to draw horizontal lines: a peculiar constructional
      disorder.
AB  - A patient is described who was affected by degenerative dementia and who
      developed severe constructional apraxia. She showed a dissociation between the
      construction of horizontal lines (impaired) and oblique or vertical lines
      (spared) which has never been reported previously. A battery of tests disclosed
      that this phenomenon was consistent across a range of experimental conditions and
      that a similar dissociation was evident in perceptual and representational
      domains. This peculiar clinical finding suggests that mental representations of
      horizontal and vertical spatial relations in an egocentric coordinate system are
      functionally dissociated.

PMID- 9647315
TI  - Persistent loss of tyrosine hydroxylase immunoreactivity in the substantia nigra
      after neuroleptic withdrawal.
AB  - A 37 year woman developed neuroleptic induced parkinsonism that persisted long
      after the drug had been discontinued. This prompted a study of the effect of an
      eight week course of haloperidol (HAL) followed by two week withdrawal, on
      dopaminergic neurons of the substantia nigra in rats. Animals treated with HAL
      showed a highly significant 32%-46% loss of tyrosine hydroxylase (TH)
      immunoreactive neurons in the substantia nigra, and 20% contraction of the TH
      stained dendritic arbour. Neuroleptic drug induced downregulation of nigral
      dopaminergic neurons may help to explain the persistent parkinsonism found in
      many patients after withdrawal of medication.

PMID- 9647316
TI  - Intracranial haemodynamics during attenuated responses to electroconvulsive
      therapy in the presence of an intracerebral aneurysm.
AB  - OBJECTIVES: This report describes successful anaesthesia and electroconvulsive
      therapy (ECT) in a patient with an unruptured basilar artery aneurysm. ECT is
      associated with a hyperdynamic state characterised by arterial hypertension,
      tachycardia, and considerably increased cerebral blood flow rate and velocity.
      These responses pose an increased risk for subarachnoid haemorrhage when an
      intracranial aneurysm coexists. METHODS: A 54 year old woman presented for ECT.
      She had a 20 year history of major depression which was unresponsive to three
      different antidepressant drugs. There was also an unruptured 5 mm saccular
      aneurysm at the basilar tip, which had been documented by cerebral angiography,
      but its size had remained unchanged for the previous four years. After she
      declined surgical intervention, she gave informed consent for ECT. During a
      series of seven ECT sessions middle cerebral artery flow velocity was recorded by
      a pulsed transcranial Doppler ultrasonography system. She was pretreated with 50
      mg oral atenolol daily, continuing up to the day of the last ECT and immediately
      before each treatment, sodium nitroprusside was infused at a rate of 30
      microg/min, to reduce systolic arterial pressure to 90-95 mm Hg. RESULTS:
      Systolic flow velocity during the awake state ranged from 62-75 cm/s, remaining
      initially unchanged with sodium nitroprusside infusion. After induction of
      anaesthesia (0.5 mg/kg methohexitone and 0.9 mg/kg succinylcholine), flow
      velocities decreased to 39-54 cm/s, reaching maximal values of 90 cm/s (only 20%
      above baseline) after ECT. These flow velocities recorded post-ECT were
      considerably below the more than twofold increase recorded when no attenuating
      drugs were used. Systolic arterial blood pressure reached maximal values of 110
      140 mm Hg and heart rate did not exceed 66 bpm. Rapid awakening followed each
      treatment, no focal or global neurological signs were apparent, and the patient
      was discharged in remission. CONCLUSION: In a patient with major depression and a
      coexisting intracerebral saccular aneurysm who was treated with ECT, the
      combination of beta blockade with atenolol and intravenous infusion of sodium
      nitroprusside prevented tachycardia and hypertension, and greatly attenuated the
      expected increase in flow velocity in the middle cerebral artery.

PMID- 9647317
TI  - Schroeder van der Kolk: the soul and epilepsy.

PMID- 9647318
TI  - Dopa responsive dystonia with Turner's syndrome: clinical, genetic, and
      neuropsychological studies in a family with a new mutation in the GTP
      cyclohydrolase I gene.
AB  - A 26 year old woman with dopa responsive dystonia and cytogenetically confirmed
      Turner's syndrome had bilateral globus pallidus hypointensity on brain MRI. Among
      the living members of a five generation pedigree the patient's mother and the
      mother's sister also had dopa responsive dystonia; a maternal grandfather had
      senile parkinsonism, his niece isolated postural tremor. No other family member
      had Turner's syndrome. A new missense mutation in exon I of the gene of GTP
      cyclohydrolase I was found in the three family members with dopa responsive
      dystonia. With levodopa substitution the patients with dopa responsive dystonia
      improved clinically as well as in quantitative tests on hand tapping, verbal and
      performance IQ, concept formation, and set shifting abilities.

PMID- 9647319
TI  - Ultrastructural characterisation of the M protein in nerve biopsy of patients
      with POEMS syndrome.
AB  - To learn more about the mechanisms of nerve lesions in POEMS syndrome, nerve
      specimens from four patients were studied with an immunogold method at the
      ultrastructural level to detect and localise the M protein in the different nerve
      compartments. An indirect immunolabelling technique was applied on 4% PFA fixed
      and LR White embedded nerve specimens. Antisera against IgG, IgA, IgM, and lambda
      and kappa light chains were used as primary antisera. Morphological studies
      disclosed an important axonal loss in association with the demyelinative process.
      Endoneurial deposits of immunoglobulins were found in all cases. In the patient
      with the most severe form of neuropathy, diffuse deposits were present in the
      endoneurial space, especially in the subperineurial area. In the other patients,
      occasional deposits of the M protein were found in the myelin sheath (n=2); or
      between cells (n=1). No deposit was found in the axons. The class of the M
      protein labelled in the nerve corresponded to that detected in the serum in three
      of four patients, with labelling of two heavy chains in one patient.
      Immunolabelling of the M protein on the myelin sheath, Schwann cells, and in the
      endoneurial space favour a direct role of the M component in the lesions of nerve
      fibres, and justify active treatment of the plasmacytic proliferation.

PMID- 9647320
TI  - An unusual enhancement of motor performance during bimanual movement in
      Parkinson's disease.
AB  - In both clinical and laboratory tests, patients with Parkinson's disease have
      considerable difficulty in performing different manual tasks simultaneously with
      the two hands. The present study reports on an unusual enhancement in performance
      under such conditions in a substantial proportion of patients tested. When
      performed at the same time as repetitive tapping tasks, the ability to rapidly
      place pegs in holes improved in almost half of the patients compared with
      unimanual performance of the peg task. Various possible explanations are
      considered for this unusual finding. The two most plausible, and testable, relate
      to either the withdrawal of attention from the task permitting a more automatic
      mode of execution, or a facilitation provided by sensory feedback from the
      simultaneous tapping task.

PMID- 9647321
TI  - Age of onset in patients with Alzheimer's disease with different apoE genotypes.

PMID- 9647322
TI  - Sudden bilateral deafness: lateral inferior pontine infarction.

PMID- 9647323
TI  - Surgical treatment of quadrigeminal plate lipoma presenting with seizures and
      behavioural disorders.

PMID- 9647324
TI  - Lambert-Eaton myasthenic syndrome and non-pulmonary small cell carcinoma.

PMID- 9647325
TI  - Untreated hepatitis C may provoke myasthenia gravis.

PMID- 9647326
TI  - Does nitric oxide regulate smooth muscle cell proliferation? A critical
      appraisal.
AB  - Smooth muscle proliferation is involved in the pathogenesis of atherosclerosis,
      restenosis after angioplasty and vein graft failure due to neointimal
      hyperplasia. Nitric oxide (NO) inhibits smooth muscle cell growth in vitro and
      experimental neointimal hyperplasia in vivo, suggesting a role for NO as a
      regulator of smooth muscle cell proliferation. NO is also involved in the control
      of numerous other vascular functions including platelet and inflammatory cell
      adhesion, vascular reactivity and endothelial permeability. This review
      critically examines the experimental and clinical evidence that supports a role
      for NO as a modulator of smooth muscle cell proliferation, with an emphasis on
      the multiple mechanisms by which NO acts on vascular lesions.

PMID- 9647327
TI  - Regulation of insulin-like growth factor-1 expression in vascular endothelial
      cells by the inflammatory cytokine interleukin-1.
AB  - Insulin-like growth factor-1 (IGF-1) has important roles in vascular physiology
      and pathologies such as atherosclerosis. However, the factors that control
      expression of this growth factor in human vascular cells are largely unknown. In
      this study the effects of the inflammatory cytokine interleukin-1 (IL-1) on IGF-1
      mRNA and peptide synthesis was examined in human endothelial cells. Cultured
      human umbilical vein endothelial (HUVE) cells were challenged with interleukin-1
      and IGF-1 Ea and Eb mRNA levels were determined by nuclease protection assays and
      reverse transcription/polymerase chain reaction. IL-1 caused a dramatic increase
      in IGF-1 Ea mRNA in HUVE cells. Transcript levels peaked between 2 and 4 h of IL
      1 treatment and declined over the subsequent 4 h. Consistent with its effect on
      mRNA, the inflammatory cytokine causes a 3-fold stimulation in production of IGF
      1 peptide from endothelial cells. These results demonstrate increased IGF-1 mRNA
      and peptide in vascular endothelial cells stimulated with IL-1. This suggests
      that under conditions of local inflammation at the vessel wall the direct action
      of IL-1 on endothelium can lead to induction of IGF-1 which could promote the
      intimal hyperplasia often seen in these circumstances.

PMID- 9647328
TI  - Expression of mRNA for phospholipase A2, cyclooxygenases, and lipoxygenases in
      cultured human umbilical vascular endothelial and smooth muscle cells and in
      biopsies from umbilical arteries and veins.
AB  - Arachidonic acid (AA) is released by phospholipase A2 (PLA2) and then converted
      into vasoactive and inflammatory eicosanoids by cyclooxygenases (COX) and
      lipoxygenases (LOX). These eicosanoids are important paracrine regulators of
      vascular permeability, blood flow, local pro- and anticoagulant activity and they
      play a major role in the local inflammatory response. We have investigated the
      presence of mRNAs for PLA2 and for isoforms of COX and LOX in both human
      endothelial cells (EC) and in human smooth muscle cells (SMC) in culture and in
      vascular biopsies of human umbilical veins (HUVB) and arteries (HUAB) by using
      the reversed transcription-polymerase chain reaction (RT-PCR) technique. Results
      show detectable levels of PLA2 type IV (cPLA2) in cultured EC and SMC and in
      vascular wall biopsies from HUAB and HUVB. The cultured EC and SMC demonstrate
      higher levels of both COX-1 and COX-2 with PCR analyses than do vascular wall
      biopsies from HUAB and HUVB. This indicates a difference in the native expression
      of COX-1 and COX-2 in cultures of EC and SMC compared to that in biopsies from
      intact vessel walls. The EC and SMC in culture do not express mRNA for 5-LOX,
      that was, however, expressed in the vascular wall biopsies. This speaks in favour
      of a constitutive, i.e. in vivo expression of 5-LOX in SMC in the vascular wall
      of both umbilical vein and arteries. Thus results from in vitro studies of
      constitutive COX and LOX expression in EC and vascular SMC in culture cannot
      simply be extrapolated to represent in vivo conditions.

PMID- 9647329
TI  - A platelet-activating factor antagonist (WEB 2170) preserves endothelium
      dependent vasodilatation and prevents development of a neo-intima induced by a
      periarterial collar in rabbit carotid arteries.
AB  - Platelet-activating factor (PAF) may be involved in adhesion of leucocytes and
      migration of cells during vascular remodelling for it is expressed in leucocytes
      after cytokine priming and is required for cell adhesion. We studied the effects
      of WEB 2170, a potent PAF antagonist, on the development of an atheroma-like neo
      intima induced by a peri-arterial collar in rabbits. Either WEB 2170 (3
      mg/kg/day) or vehicle was given by subcutaneous injection once a day for 4 or 9
      days, and on day 3 peri-arterial collars were applied to both carotid arteries in
      all animals. Two or 7 days after implanting the collars vasodilator responses to
      the endothelium-dependent vasodilator, acetylcholine and the endothelium
      independent vasodilator, sodium nitroprusside were studied in isolated artery
      rings from both groups of rabbits. Neo-intima formation after 7 days (day 10 of
      treatment) was measured by light microscopy as the ratio of cross-sectional areas
      of intima and media, and expression of inducible nitric oxide synthase (iNOS) was
      studied by immunohistochemistry. PAF-induced platelet aggregation ex vivo was
      inhibited specifically in WEB 2170-treated rabbits. At day 5, acetylcholine
      induced vasorelaxation in collared artery rings was markedly impaired as compared
      to control sections from both vehicle- and WEB 2170-treated rabbits. At day 10,
      acetylcholine-induced vasorelaxation in collared artery rings from vehicle
      rabbits was markedly less than in controls, but in WEB 2170-treated rabbits, the
      acetylcholine response in collared arteries was similar to control sections.
      Intimal thickening was much reduced in WEB 2170-treated rabbits, ratios of
      intima/media areas being vehicle: 0.21 +/- 0.02 (n = 5) and WEB 2170: 0.07 +/-
      0.01 (n = 7; p < 0.01). Immunofluorescence showed expression of iNOS only in the
      neo-intima of vehicle-treated, collared arteries, but not in the residual neo
      intima of WEB 2170-treated, collared arteries. These results suggest that WEB
      2170 is effective in preserving endothelial function, prevents the development of
      neo-intima and blocks iNOS expression in the neo-intima in this model.

PMID- 9647330
TI  - Inhibition of vascular smooth muscle cell migration by intact endothelium is
      nitric oxide-mediated: interference by oxidised low density lipoproteins.
AB  - Migration of vascular smooth muscle cells (SMCs) leading to neointimal
      hyperplasia is an early and cardinal feature of atherogenesis. Migration of rat
      aortic SMCs from an upper chamber towards a lower one has been studied in a
      microchemotaxis (Boyden) chamber. Spontaneous migration of SMCs was practically
      prevented by the presence of endothelium in the lower chamber and was reduced if
      endothelial cells were substituted with endothelial cell-conditioned medium.
      Endothelial cells which had been treated with either the inhibitor of protein
      synthesis cycloheximide or nitric oxide synthesis N(G)-nitro-L-arginine showed no
      inhibitory effect on SMC migration. Addition of a nitric oxide donor S-nitroso-N
      acetylpenicillamine to cell-free medium in the lower chamber prevented SMC
      migration. Addition of native LDL to endothelial cells had no effect on SMC
      migration, while (UV light) oxidised LDL completely abolished the inhibitory
      effect of endothelial cells on SMC migration. It is concluded that via nitric
      oxide, endothelium exerts a powerful inhibitory effect on SMC migration. This
      effect of intact endothelium is completely abolished by oxidised LDL applied in a
      concentration, which is relevant to those measured in plasma of patients with
      severe coronary artery disease. It is suggested that oxidised LDL may contribute
      to the pathogenesis of atherogenesis by stimulating migration of SMCs from media
      to the intima via abolishing the physiological inhibitory effect of normal
      endothelium.

PMID- 9647331
TI  - Reactivity of small intramyocardial arteries from atherosclerotic and non
      atherosclerotic human hearts.
AB  - Little is known about how the vascular reactivity of the coronary
      microcirculation is affected by upstream atherosclerotic disease. We have
      examined, with a wire myograph, the responses of intramyocardial arteries from
      hearts in which the epicardial vessels were either free of atherosclerotic
      lesions (non-diseased group) or were affected by atherosclerosis (diseased
      group). Vasodilator responses of preconstricted vessels to substance P (84.1 +/-
      12.6 compared to 42.0 +/- 19.7%) were less in vessels from the diseased group (p
      < 0.05). In contrast, the relaxation to bradykinin (70.2 +/- 21.2 compared to
      100.6 +/- 7.9%) was increased in vessels from the diseased group (p < 0.05). The
      dilator responses to acetylcholine, adenosine diphosphate, histamine and sodium
      nitroprusside showed no significant differences between arteries from each group.
      5-Hydroxytryptamine was without any significant vasodilator effect in arteries
      from either group. Assessment of contractile function revealed that the responses
      to 5-hydroxytryptamine, acetylcholine, U46619, endothelin-1 and L-N(G)
      monomethylarginine in each group were not significantly different. Histamine,
      noradrenaline and dopamine were without any significant contractile response.
      These results demonstrate that upstream atherosclerosis does not confer any
      global impairment of endothelium-dependent vasorelaxant responses or smooth
      muscle hyperreactivity to vasoconstrictors in the arteries that penetrate the
      myocardium.

PMID- 9647332
TI  - Coexpression of mRNAs for P2X1, P2X2 and P2X4 receptors in rat vascular smooth
      muscle: an in situ hybridization and RT-PCR study.
AB  - The expression of mRNAs for three P2X receptor subtypes (PX21, P2X2, P2X4) in the
      rat vascular system was studied by in situ hybridization and RT-PCR. In heart
      sections mRNAs transcripts for all three receptors were colocalized in smooth
      muscle cells of coronary vessels, while no specific positivity was apparent in
      myocardium. Coexpression of P2X receptor mRNA transcripts were also observed in
      other peripheral vessels, including aorta, pulmonary artery, internal and
      external iliac arteries, renal artery and femoral artery. By contrast, no mRNA
      transcripts of the above receptors were found in the superior mesenteric artery.
      RT-PCR performed on microdissected tissues (coronary arteries, aorta and
      myocardium from various heart areas) confirmed the presence of P2X1, P2X2 and
      P2X4 receptor mRNAs. Furthermore, in the same tissues two splice variants of the
      P2X2 receptor were identified. These results reveal an important molecular
      heterogeneity of P2X receptors, thus substantiating the possibility of a
      heteropolymeric assembly of ATP-gated ion channels in the cardiovascular system.

PMID- 9647333
TI  - Gene expression of endothelin-1 and ET(A) and ET(B) receptors in human cirrhosis:
      relationship with hepatic hemodynamics.
AB  - Previous experimental studies have suggested that the paracrine endothelin system
      may participate in the regulation of hepatic hemodynamics in cirrhosis. The
      present study assesses the relationship between increased portal pressure and
      preproET-1, ET(A) receptor and ET(B) receptor gene expression in human cirrhosis.
      PreproET-1, ET(A) receptor and ET(B) receptor mRNA abundance was estimated by
      quantitative PCR in human hepatic tissue from subjects with normal liver and in
      cirrhotic patients in whom a hepatic hemodynamic study was performed. The
      expression of the three transcripts was significantly higher in liver samples of
      cirrhotic patients than in those obtained from subjects without any histological
      alteration. Moreover, while no significant correlation was found between preproET
      1 mRNA abundance and portal pressure, there was a highly significant direct
      relationship between ET(A) and ET(B) receptor gene expression and portal pressure
      in cirrhotic patients. These results indicate that the liver paracrine endothelin
      system is overactivated in human cirrhosis and that a direct relationship exists
      between endothelin receptor mRNA abundance and the degree of portal hypertension
      in these patients.

PMID- 9647334
TI  - Effect of troglitazone on fibrinolysis and activated coagulation in patients with
      non-insulin-dependent diabetes mellitus.
AB  - The objective of this study was to determine if treatment of non-insulin
      dependent diabetes mellitus (NIDDM) patients with the "insulin sensitizer"
      troglitazone, both as monotherapy and in combination with insulin, corrects the
      impaired fibrinolysis and activated coagulation associated with NIDDM. Patients
      participating in two clinical trials comparing troglitazone and placebo in
      patients with NIDDM were studied at the time of randomization and after 26 weeks
      of treatment. Eighteen patients were treated with troglitazone (ten in
      combination with insulin and eight as monotherapy) and eight were treated with
      placebo (four in each trial). Plasma concentrations of plasminogen activator
      inhibitor (PAI-1), prothrombin fragment F1+2, fibrinogen, and von Willebrand
      Factor (vWF) activity were measured. Plasma PAI-1 concentrations fell
      significantly from a mean of 68.8 +/- 32.3 ng/mL to 40.4 +/- 20.4 in the
      troglitazone treated group, but did not change significantly in the placebo
      treated group. Plasma PAI-1 concentrations were elevated in 15 patients treated
      with troglitazone and fell to normal in eight of them. There was no significant
      change in plasma F1+2, vWF, and fibrinogen, but plasma C-peptide and triglyceride
      concentrations fell significantly with troglitazone. This study demonstrates that
      troglitazone treatment is associated with a significant fall in plasma PAI-1
      antigen concentrations in patients with NIDDM and, therefore, may have a
      beneficial effect on fibrinolysis.

PMID- 9647335
TI  - Influence of non-insulin-dependent diabetes mellitus on plasma endothelin-1
      levels in patients with advanced atherosclerosis.
AB  - Endothelin-1 (ET-1) is an endothelium-derived vasoactive peptide with mitogen
      properties. Increased circulating ET-1 levels were found in patients with
      atherosclerosis as well as in patients with non-insulin-dependent diabetes
      mellitus (NIDDM) suggesting a role in the pathogenesis of these disorders. The
      aim of the present study was to ascertain the influence of the NIDDM on plasma ET
      1 levels in patients with advanced atherosclerotic lesions. The circulating ET-1
      levels were measured in 16 NIDDM patients (68.4 +/- 8.4 years) with
      macroangiopathy and in ten patients (65.3 +/- 11 years) with atherosclerosis
      without NIDDM. Twenty-two healthy subjects (43.1 +/- 18.3 years) served as
      controls. Circulating ET-1 levels were higher in NIDDM patients (6.8 +/- 2.8
      pg/mL) than both controls (3.1 +/- 1 pg/mL; p < 0.001) and patients with vascular
      disease but without NIDDM (4.7 +/- 1.6 pg/mL; p < 0.04). No significant
      relationship was found between age and ET-1 concentrations, and no differences
      were noted between men and women in the control group. This study demonstrated
      that circulating ET-1 levels are increased in patients with atherosclerosis and
      that those with NIDDM showed the highest ET-1 levels. These observations strongly
      support a role for ET-1 in the pathogenesis of atherosclerosis and also suggest
      that this peptide may be involved in the development of atherosclerotic lesions
      in the NIDDM. We speculated that chronic exposure to hyperinsulinemia and
      hypertriglyceridemia in the diabetic patients could account for the increased ET
      1 levels found in these patients.

PMID- 9647336
TI  - Relationship of microalbuminuria with the diabetic foot ulcers in type II
      diabetes.
AB  - Microalbuminuria is a significant risk factor associated with nephropathy,
      retinopathy, and cardiovascular disease; however, there are no previous reports
      on the relationship of microalbuminuria with diabetic foot ulcers or stroke,
      despite the fact that microalbuminuria is a marker of vascular damage. The
      purpose of this study was to determine the relationship of microalbuminuria with
      diabetic foot ulcers in type II diabetes patients. In this, cross-sectional
      clinical study, outpatients of the offices at first level medical care in
      Durango, Mexico, were included in one of two groups; (a) patients with diabetic
      foot ulcers and (b) control of group patients without diabetic foot ulcers.
      Diabetic foot diagnosis was established on the basis of clinical criteria and
      pletismography. Patients diagnosed with renal disease, urinary tract infection,
      acute febrile illness, or heart failure and those receiving angiotensin
      converting enzyme inhibitors were excluded from the study. Microalbuminuria was
      measured, on a 24-h urine collection, by precipitation with sulfasalicylic acid,
      and turbidity was determined by measuring absorbance with a spectrophotometer.
      The study included 670 diabetic patients. Using both odds ratio and logistic
      regression analyses, diabetes duration, cigarette smoking, aging, and
      microalbuminuria showed a strong relationship with diabetic foot ulcers.
      Microalbuminuria should be considered as an independent risk factor for diabetic
      foot ulcers.

PMID- 9647337
TI  - Impact of diabetes mellitus on infrainguinal bypass grafting.
AB  - The purpose of this study was to examine the role of diabetes mellitus (DM) in
      infrainguinal bypass graft outcome. One hundred forty-four patients who underwent
      170 infrainguinal bypass grafts from 1990 to 1995 were reviewed retrospectively.
      Seventy-eight patients (94 bypasses) had DM and were followed for an average of
      15.4 months; 13 patients were lost to follow up. The mean age was 68 years; 44
      (56.4%) were men. The major indication for intervention was limb salvage for the
      DM (87/94, 92.6%) and non-DM (56/76, 73.7%) groups. No significant difference was
      found for perioperative wound complications, hematoma, myocardial infarction, or
      deep venous thrombosis between the DM and non-DM groups. Early mortalities were
      three for DM and one for non-DM patients. No significant difference was found
      between primary patency (p = 0.71), secondary patency (p = 0.32), limb salvage (p
      = 0.99), and survival (p = 0.72) between DM and non-DM groups. DM patients were
      more likely to have significant tissue loss (p = 0.009) and a longer hospital
      stay (p = 0.01). In conclusion, infrainguinal vein bypass grafting can be
      performed successfully in diabetic patients with comparable patency and limb
      salvage rates to those without DM.

PMID- 9647338
TI  - Effect of aldose reductase inhibition on cardiovascular reflex tests in patients
      with definite diabetic autonomic neuropathy over a period of 2 years.
AB  - The potential of the aldose reductase inhibitor tolrestat to ameliorate definite
      diabetic autonomic neuropathy (DAN), as defined by standard cardiovascular
      autonomic function tests, was evaluated in 35 patients over a period of 2 years,
      with repeated measurements at 3-month intervals. The effect of tolrestat (200 mg
      a day) was compared with that of placebo on 35 controls with diabetes mellitus,
      of similar age, gender, and glycemic control. In the placebo group, a significant
      deterioration of the indices, with the exception of Valsalva ratio, was recorded,
      while tolrestat induced a significant beneficial change in the values of most
      standard cardiovascular reflex tests, in comparison to baseline and placebo. The
      deep breathing tests (expiration-inspiration ratio, standard deviation, and mean
      circular resultant of R-R intervals), postural index, and postural hypotension
      were favorably affected. Three of 35 patients on tolrestat (8.6%) developed high
      transaminases levels (more than threefold the upper normal limit) and were
      withdrawn from the study. In conclusion, tolrestat improved autonomic nervous
      system function in patients with definite DAN, in comparison to baseline and
      placebo. The clinical importance of this finding needs further investigation.

PMID- 9647339
TI  - Long-term intraindividual variability of serum lipids in patients with type I and
      type II diabetes.
AB  - The objective of this study was to estimate the long-term intraindividual
      variability of lipid levels in adult type I and type II diabetic patients. Total
      cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, low
      density lipoprotein (LDL) cholesterol, and hemoglobin A1c were measured every 3-6
      months in 135 patients attending the Austin Hospital diabetes clinic. Analysis
      was performed on 60 diabetic patients (33 type I and 27 type II) who had not been
      treated with lipid lowering drugs and who met the inclusion criteria of at least
      five measurements [mean +/- standard error of the mean (SEM), 9.5 +/- 0.4; range,
      5-17] collected over a minimum of 4 years (5.1 +/- 0.1; 4-6.5 years). Total
      variability, expressed as coefficient of variation, was 8.8 +/- 0.4% for total
      cholesterol, 23.9 +/- 1.5% for triglycerides, 10.2 +/- 0.5% for HDL cholesterol,
      and 12.0 +/- 0.5% for LDL cholesterol. Biological variability, derived from total
      and analytical variability, was higher than previous estimates in nondiabetic
      subjects for total cholesterol and HDL cholesterol but similar for triglycerides
      and LDL cholesterol. No relationship was observed between total lipid variability
      and diabetes type, age, baseline or mean lipid levels, duration of follow-up, or
      the number of samples per patient. Men demonstrated greater variability than
      women for total cholesterol (men 9.5 +/- 0.5%, n = 34, women 7.9 +/- 0.5%, n =
      26, p < 0.01) and triglycerides (men 26.5 +/- 2.2%, women 20.4 +/- 1.4%, p =
      0.03). Total lipid variability was also unrelated to baseline or mean hemoglobin
      A1c or to the change in hemoglobin A1c during the study as a whole. However, the
      change in hemoglobin A1c was associated with the change in total cholesterol (r =
      0.30, p < 0.03) and the change in LDL cholesterol (r = 0.27, p < 0.05). In
      conclusion, long-term intraindividual lipid variability in adult diabetic
      subjects is higher for total and HDL cholesterol than previously published values
      in nondiabetic subjects. Variability of triglycerides is at least double that of
      total cholesterol, HDL cholesterol and LDL cholesterol. Biological variability,
      not measurement error, accounts for the greatest proportion of total variability
      for all lipid parameters. Confidence levels calculated from these data have
      implications for the initiation of lipid lowering therapy and in monitoring the
      effects of intervention.

PMID- 9647340
TI  - Abnormalities of small intestinal endocrine cells in non-obese diabetic mice.
AB  - The endocrine cells in the duodenum of pre-diabetic and diabetic female non-obese
      diabetic (NOD) mice aged 22-24 weeks were studied by means of
      immunohistochemistry and computed image analysis as well as by radioimmunoassays
      of tissue extracts. As controls, 12 female BALB/cJ mice of the same age as NOD
      mice were used. The number of secretin-immunoreactive cells increased in diabetic
      but not in pre-diabetic NOD mice. The level of extractable secretin was higher in
      both pre-diabetic and diabetic NOD mice. The number of GIP-, CCK/gastrin-, and
      serotonin-immunoreactive cells was significantly reduced in both pre-diabetic and
      diabetic NOD mice. There was no statistical difference in the number of
      somatostatin-immunoreactive cells between the NOD mice and controls. The level of
      GIP was higher and gastrin was lower in NOD mice compared to controls. There was
      no statistical difference in the somatostatin level between the NOD mice and
      controls. The cell secretory index was elevated in all the endocrine cell types
      except CCK/gastrin cells. It has been suggested that some of the changes in the
      duodenal endocrine cells could be attributed to the diabetes state, but most of
      the changes seem to take place before the onset of diabetes. The abnormalities in
      the duodenal endocrine cells observed here in an animal model for diabetes type I
      might have relevance for the gastrointestinal dysfunction displayed in human
      diabetes.

PMID- 9647341
TI  - A case of fatal rhinocerebral mucormycosis with new onset diabetic keto-acidosis.

PMID- 9647342
TI  - The role of acarbose in the treatment of non-insulin-dependent diabetes mellitus.
AB  - Acarbose is the first of a new class of antidiabetic agents, the alpha
      glucosidase inhibitors. Acarbose has proven effectiveness as a first-line drug in
      type 2 diabetes insufficiently controlled by diet alone. In addition to providing
      short-term glycemic control, acarbose also reduces HbA1c levels. This effect is
      greatest when therapy is initiated early in the disease and when baseline HbA1c
      levels are high. Depending on the baseline HbA1c value, therapeutic doses of
      acarbose lead to a HbA1c reduction of 0.5%-1.2%. Acarbose may be safely combined
      with all oral hypoglycemic agents, and has been found to have utility as an
      adjunct to sulfonylurea and metformin therapy. It also improves control of
      insulin-treated type 2 diabetes and enables a reduction of exogenous insulin
      requirements of up to 30%. Acarbose also has beneficial effects on the coronary
      risk factors, e.g. postprandial triglyceride levels, elevated cholesterol, and
      hyperinsulinemia. The early phase of acarbose therapy may be associated with side
      effects such as meteorism, flatulence, and diarrhea. These result from the local
      effect of the drug and decline with time. To date, there have been no reports of
      systemic toxicity. Acarbose does not cause hypoglycemias or weight gain.

PMID- 9647343
TI  - Genetic engineering of protein-based polymers: potential in controlled drug
      delivery.

PMID- 9647344
TI  - Oligopeptide transporters as putative therapeutic targets for cancer cells.

PMID- 9647345
TI  - Intracellular phosphorylation of zidovudine (ZDV) and other nucleoside reverse
      transcriptase inhibitors (RTI) used for human immunodeficiency virus (HIV)
      infection.
AB  - Dramatic reductions of viral load and increased survival have been achieved in
      patients infected with the Human Immunodeficiency Virus (HIV) with the
      introduction of combination antiretroviral therapy. Currently 11 agents including
      nucleoside reverse transcriptase inhibitors (RTI), non-nucleoside RTI and
      protease inhibitors are available for the use for treatment of HIV infection.
      Recent studies have demonstrated that certain combinations of these drugs are
      advantageous over their individual use as monotherapy with an even more sustained
      viral suppression. Much emphasis has therefore been put on studies evaluating the
      interactions of these different compounds. Especially the intracellular
      metabolism of nucleoside RTI has been evaluated to some extent, by both in vitro
      and in vivo studies. These compounds need to undergo phosphorylation to their
      active 5'-triphoshates involving several enzymatic steps and the nucleoside
      concentration in the plasma may not correlate with intracellular concentrations
      of active drug. It is therefore of great importance to study these drugs at an
      intracellular level in order to evaluate their efficacy. This review summarizes
      the intracellular phosphorylation of Zidovudine and other nucleoside analogs
      investigated by in vitro experiments and the efforts of measuring the active
      anabolites in vivo in cells isolated from HIV infected patients on nucleoside
      therapy.

PMID- 9647347
TI  - The molecular mobility of supercooled amorphous indomethacin as a function of
      temperature and relative humidity.
AB  - PURPOSE: To determine the relaxation times of supercooled indomethacin as a
      function of temperature and relative humidity above Tg, and to analyze the
      results in the context of being able to predict such behavior at various storage
      conditions. METHODS: Dielectric relaxation times were measured in the frequency
      domain (12 to 10(5) Hz) for amorphous indomethacin equilibrated at 0, 56, and 83%
      relative humidity. The heating rate dependence of Tg for dry supercooled
      indomethacin was measured with differential scanning calorimetry and used to
      determine relaxation times. The results were compared with previously published
      shear relaxation times and enthalpy recovery data. RESULTS: Very good agreement
      was observed between dielectric and shear relaxation times, and those obtained
      from the heating rate dependence of the Tg, for dry indomethacin as a function of
      temperature above Tg. The introduction of water lowered the dielectric relaxation
      times of supercooled indomethacin without significantly affecting its fragility.
      The relaxation times below Tg, found to be lower than those predicted by
      extrapolation of the data obtained above Tg, were analyzed in the context of the
      Adam-Gibbs-Vogel equation. CONCLUSIONS: The relaxation times of amorphous
      indomethacin obtained from the heating rate dependence of Tg were in good
      agreement with those obtained from shear and dielectric measurements, thus
      validating a relatively simple approach of assessing molecular mobility. The
      significant molecular mobility of amorphous indomethacin observed below Tg, and
      the significant plasticizing effects of sorbed water, help to explain why
      amorphous indomethacin crystallizes well below Tg over relatively short time
      scales.

PMID- 9647346
TI  - Recent advances in intestinal macromolecular drug delivery via receptor-mediated
      transport pathways.
AB  - Receptor-mediated transport mechanisms provide a pathway for the trafficking of
      extracellular macromolecules into (endocytosis) and across (transcytosis) the
      cell. This comprises the binding of a ligand to a specific cell-surface receptor,
      clustering of the ligand-receptor complexes in endocytotic vesicles and vesicular
      sorting. This review focuses on recent advances in cellular and molecular biology
      pertaining to receptor-mediated endocytosis. A concise overview is presented of
      current and potential future applications of targeting to RME mechanisms to
      improve oral macromolecular drug delivery.

PMID- 9647348
TI  - Bond cleavage reactions in solid aqueous carbohydrate solutions.
AB  - PURPOSE: To investigate chemical reactivity in water soluble glasses. METHODS:
      Rates of bond cleavage reactions in freeze-dried and freeze-concentrated aqueous
      carbohydrate solutions were measured above and below the glass transition
      temperatures (Tg). The kinetics of two reactions have been determined in
      formulations containing di- and polysaccharides: (1) fission of the Asp-Pro
      peptide bond in Physalaemin and Hamburger peptide by following the release of
      proline, using a ninhydrin based reaction and (2) the unimolecular dissociation
      of 2-(4-nitrophenoxy) tetrahydropyran by following the release of the 4
      nitrophenoxy anion. RESULTS: The results show clearly that reaction occurs below
      the glass transition temperature, albeit at very reduced rates. No significant
      enhancement of the temperature dependence of the rate constant was observed near
      Tg. Different water soluble glasses provide different degrees of stability. The
      order of stabilisation was sucrose>Ficoll (low mol. weight)>Byco A approximately
      equal to Ficoll (high mol. weight)>dextran. The density of the matrix, and
      therefore the degrees of freedom of mobility of the reactant, is thought to be
      responsible for these differences. CONCLUSIONS: The storage of therapeutic
      agents, such as proteins, in glassy matrices below Tg does not confer indefinite
      stability. When formulating products, notice should be taken of the differing
      stabilisation properties of excipients.

PMID- 9647349
TI  - Effects of pluronic block copolymers on drug absorption in Caco-2 cell
      monolayers.
AB  - PURPOSE: The present work characterizes the effects of Pluronic copolymers on the
      transport of a P-gp-dependent probe, rhodamine 123 (R123) in Caco-2 cell
      monolayers. METHODS: The accumulation and efflux studies were performed on the
      confluent Caco-2 monolayers using fluorescent probes with and without Pluronic
      copolymers. RESULTS: At concentrations below the critical micelle concentration
      single chains ("unimers") of Pluronic P85 enhanced the accumulation and inhibited
      the efflux of R123 in Caco-2 monolayers. The transport of the P-gp-independent
      probe, rhodamine 110 was not altered under these conditions. In contrast the
      micelles increased R123 accumulation to a much lower extent when compared to the
      unimers and enhanced R123 efflux in Caco-2 monolayers. CONCLUSIONS: Pluronic P85
      unimers increase accumulation of a P-gp-dependent drug in Caco-2 monolayers
      through inhibition of the P-gp efflux system. The mechanism of the micelle effect
      is not known, however, it is very similar to the micelle effects in BBMEC. This
      has been previously shown to involve vesicular transport of the micelle
      incorporated drug. The study suggests that Pluronic copolymers can be useful in
      increasing oral absorption of select drugs.

PMID- 9647350
TI  - Jejunal absorption and metabolism of R/S-verapamil in humans.
AB  - PURPOSE: The purpose of this human intestinal perfusion study was to investigate
      the transport and metabolism of R/S-verapamil in the human jejunum (in vivo).
      METHODS: A regional single-pass perfusion of the jejunum was performed using a
      Loc-I-Gut perfusion tube in 12 healthy volunteers. Each perfusion lasted for 200
      min and was divided into two periods each of 100 min. The inlet concentrations of
      verapamil were 4.0 and 40 mg/l in period one and two, respectively. RESULTS: The
      effective jejunal permeability (Peff) of both R- and S-verapamil increased (p <
      0.05) when the inlet concentration was increased consistent with saturation of an
      efflux mechanism. However, both R- and S-verapamil had high intestinal Peff,
      consistent with complete absorption. The Peff of antipyrine also increased, but
      there was no difference in the Peff for D-glucose in the two periods. The
      appearance of R/S-norverapamil in the intestinal perfusate leaving the jejunal
      segment was non-linear, presumably due to saturation of the CYP3A4 metabolism.
      CONCLUSIONS: The increased Peff in parallel with increased entering drug
      concentration is most likely due to saturable efflux by P-glycoprotein(s) in the
      human intestine.

PMID- 9647351
TI  - Interaction of a self-emulsifying lipid drug delivery system with the everted rat
      intestinal mucosa as a function of droplet size and surface charge.
AB  - PURPOSE: To investigate the interaction of positively charged self-emulsifying
      oil formulations (SEOF) following aqueous dilution as a function of resulting
      emulsion droplet charge and size with rat everted intestinal mucosa, adherent
      mucus layer and Peyer's patches, using cyclosporine A (CsA) as a lipophilic model
      drug. METHODS: Droplet size determination (TEM technique) and zeta-potential
      measurements were used to characterize the resulting emulsions. For the ex vivo
      interaction study, the well-known rat intestine everted sac technique was used in
      combination with confocal microscopy. RESULTS: The positively charged oil
      droplets formed by SEOF dilutions at ratios of 1/50 and 1/10 elicited the
      stronger interaction with the mucosal surface. The positive charge of the smaller
      droplets was more readily neutralized, and even reversed in aqueous solutions
      containing moderate subphysiological mucin concentrations. Parameters such as
      droplet size, negativity of the epithelial mucosa potential and presence of the
      mucus layer on the epithelial surface affected drug mucosa uptake and the
      adhesion of the positively charged droplets to the rat intestinal mucosa.
      CONCLUSIONS: The enhanced electrostatic interactions of positively charged
      droplets with the mucosal surface are mostly responsible for the preferential
      uptake of CsA from the positively charged droplets as compared to negatively
      charged droplets irrespective of the experimental conditions used. The increased
      uptake of the CsA from the negatively charged oil droplets was consistent with
      the dilution extent, as expected, whereas in the positively charged droplets, an
      intermediate droplet size range was identified resulting in optimum drug uptake
      and clearly suggesting that drug uptake was not consistent with either dilution
      extent or droplet size.

PMID- 9647352
TI  - Nitric oxide donors enhance rectal absorption of macromolecules in rabbits.
AB  - PURPOSE: The objective of this investigation is to evaluate the potential of
      nitric oxide (NO) donors as a new class of absorption enhancers which may act on
      intestinal epithelial cells through epithelial actions of the chemical mediator,
      NO. METHODS: Suppositories containing NO donors and insulin were administered
      into the rabbit rectum. After administration of the suppository, blood samples
      were collected from the auricular vein. The plasma insulin and glucose
      concentrations were determined. RESULTS: The NO donor S-nitroso-N-acetyl-DL
      penicillamine (SNAP, 4 mg) induced a significant increase in the rate of insulin
      absorption from the rectum. Administration of a suppository containing SNAP
      without insulin affected neither the plasma insulin nor the plasma glucose
      concentration. Other NO donors, NOR1 and NOR4, also induced increases in the
      insulin absorption. The absorption enhancement effect of SNAP was inhibited by
      coadministration of the NO scavenger carboxy-PTIO. SNAP also enhanced FITC
      dextran (MW 4,000) absorption. Little cytotoxicity of SNAP (3.0 mg/ml) as
      assessed in terms of the rate of lactate dehydrogenase (LDH) release from Caco-2
      cells was detected for 2 h of incubation. CONCLUSIONS: These findings suggest
      that NO enhanced macromolecular absorption from the rectum without mucosal cell
      damage, and that NO donors can act as potent absorption enhancers.

PMID- 9647353
TI  - Pharmacokinetics of the transdermal reservoir membrane system delivering beta
      estradiol: in vitro/in vivo-correlation.
AB  - PURPOSE: The aim of our study was to investigate the high fluctuations of
      Estradiol (E2) plasma levels transdermally delivered in postmenopausal women by a
      commercially available membrane controlled reservoir system (MCRS). METHODS: The
      transdermal E2 flux either out of a complete MCRS or across its membrane out of
      defined ethanol water mixtures was determined, as well as E2 plasma profiles in 6
      postmenopausal women produced by a MCRS. RESULTS: The transdermal in vitro E2
      flux rate out of a complete MCRS, claimed to deliver 25 microg/day, increased
      steadily, reaching a maximum value of 2.06 +/- 0.58 microg/h at 30 to 40 hours
      and decreased to a rate of about 0.5 microg/h from 60 to 90 hours. No
      statistically significant differences between plasma profiles calculated from the
      in vitro investigation and derived from a clinical study could be identified. The
      E2 flux in defined ethanol/water mixtures across MCRS-membrane, adhesive and skin
      layer increased with increasing ethanol concentrations up to a maximum of 227 +/-
      34 ng/cm2/h at an ethanol concentration of 62.5% (V/V) and decreased with further
      increase in the volume fraction of ethanol. CONCLUSIONS: In vitro as well as in
      vivo investigations showed high fluctuation of E2 plasma profiles in
      postmenopausal women produced by the MCRS. These fluctuations are caused by a non
      constant input rate of E2 which may be due to changing ethanol concentrations in
      the reservoir of the MCRS.

PMID- 9647354
TI  - Skin mini-erosion sampling technique: feasibility study with regard to serial
      glucose measurement.
AB  - PURPOSE: To describe a dermally non-invasive serial sampling technique and to
      test its clinical feasibility with regard to glucose measurement. METHODS: A
      standardized skin mini-erosion devoid of the epidermal barrier, and covered by an
      artificial one, was formed by a suctioning technique. Interstitial fluid (IF) was
      extracted serially by brief application of negative pressure, and its glucose
      content compared with that in capillary or venous blood samples. RESULTS: The
      procedure caused no discomfort. The epidermis regenerated rapidly after
      experimentation. There were no complications. In non-diabetic subjects (n = 13)
      the mean of all IF values measured daily for 6 days was 6.2 +/- 0.1 mmol/l (+/
      SE). The corresponding capillary blood glucose value was 5.6 +/- 0.1 mmol/l, and
      the venous glucose value was 5.4 +/- 0.1 mmol/l. The differences between IF
      glucose values and invasive control values remained within narrow limits
      throughout. The 2SD limits of agreement for the differences were 1.44 mmol/l (IF
      vs. capillary blood samples) and 1.76 mmol/l (IF vs venous samples) respectively.
      The OGTT curves suggested glucose kinetics to be similar in IF and in capillary
      blood. In diabetic subjects, the mean of IF values determined serially during one
      day was 15.3 +/- 1.0 mmol/l (range, 6.7-21.8 mmol/l), and the corresponding mean
      capillary value was 12.0 +/- 0.9 mmol/l (range, 3.3-17.2 mmol/l). The ICC for all
      paired photometric observations was 0.948. CONCLUSIONS: The results suggest the
      new sampling technique to be a feasible approach for clinical and experimental
      purposes. A functionally integrated sampling patch is entering the clinical
      testing stage.

PMID- 9647355
TI  - In vitro dissolution profile comparison--statistics and analysis of the
      similarity factor, f2.
AB  - PURPOSE: To describe the properties of the similarity factor (f2) as a measure
      for assessing the similarity of two dissolution profiles. Discuss the statistical
      properties of the estimate based on sample means. METHODS: The f2 metrics and the
      decision rule is evaluated using examples of dissolution profiles. The confidence
      interval is calculated using bootstrapping method. The bias of the estimate using
      sample mean dissolution is evaluated. RESULTS: 1. f2 values were found to be
      sensitive to number of sample points, after the dissolution plateau has been
      reached. 2. The statistical evaluation of f2 could be made using 90% confidence
      interval approach. 3. The statistical distribution of f2 metrics could be
      simulated using 'Bootstrap' method. A relatively robust distribution could be
      obtained after more than 500 'Bootstraps'. 4. A statistical 'bias correction' was
      found to reduce the bias. CONCLUSIONS: The similarity factor f2 is a simple
      measure for the comparison of two dissolution profiles. But the commonly used
      similarity factor estimate f2 is a biased and conservative estimate of f2. The
      bootstrap approach is a useful tool to simulate the confidence interval.

PMID- 9647356
TI  - Effect of experimental diabetes mellitus and arthritis on the pharmacokinetics of
      hydroxychloroquine enantiomers in rats.
AB  - PURPOSE: To study the effect of experimental diabetes and arthritis on the
      pharmacokinetics of hydroxychloroquine (HCQ) enantiomers in rats. METHODS: The
      pharmacokinetic studies were carried out following administration of 40 mg/kg of
      racemic HCQ to diabetic, insulin-treated diabetic, adjuvant arthritic and control
      rats. RESULTS: Renal (70% and 62% for R- and S-HCQ, respectively) and non-renal
      clearance (100% and 145% for R- and S-HCQ, respectively) of HCQ enantiomers were
      significantly increased in diabetic rats. Diabetes-induced alterations in the
      disposition of HCQ were reversed by insulin treatment. In arthritic rats,
      systemic clearance (CL) of HCQ enantiomers was significantly reduced (1.05 +/-
      0.15 and 1.3 +/- 0.19 l/h/kg for R- and S-HCQ, respectively) compared to controls
      (1.69 +/- 0.32 and 1.93 +/- 0.34 l/h/kg for R- and S-HCQ, respectively). The
      fraction unbound of the R- and S-HCQ were 49.4% and 50.5% lower in platelet rich
      plasma of arthritic rats compared to healthy rats. Increased blood concentrations
      of HCQ enantiomers in arthritic rats were significantly related to the degree of
      inflammation. CONCLUSIONS: Diabetes significantly increased the CL of both R- and
      S-HCQ by increasing renal and non-renal clearance. Arthritis caused a significant
      decrease in CL of HCQ enantiomers through increased binding and a decreased
      intrinsic clearance. The effect of the diseases on the pharmacokinetics of HCQ,
      however, was not stereoselective.

PMID- 9647357
TI  - Pharmacokinetics and biodistribution of a nucleotide-based thrombin inhibitor in
      rats.
AB  - PURPOSE: To characterize the pharmacokinetic and tissue distribution profiles of
      a nucleotide-based thrombin inhibitor (GS522, phosphodiester oligonucleotide,
      GGTTGGTGTGGTTGG) following intravenous administration to rats. METHODS:
      Pharmacokinetic study: 10 mg/kg, 20 mg/kg, 30 mg/kg (6 animals/dose) were
      administered to rats by rapid injection into the femoral vein. Blood samples were
      collected over a 45 minute period. Plasma concentrations of GS522 were determined
      using capillary gel electrophoresis with laser-induced fluorescence detection.
      Biodistribution Study: 10 mg/kg (400 microl, 31.46 microCi/ml) of 3H-GS522 was
      administered to rats by rapid injection into the femoral vein. The animals were
      sacrificed by decapitation at 1, 5, 10, 30, 60, 360 minutes post-dose (3
      rats/point). Brain, blood, duodenum, eyes, heart, kidney, liver, lungs, muscle,
      pancreas, skin, spleen and vein samples were collected, processed and quantitated
      using liquid scintillation counting. RESULTS: The pharmacokinetic profile
      declines in multiexponential manner, exhibiting extremely fast distribution and
      elimination (t1/2 = 7.6-9.0 min, Cl = 22.0-28.0 ml/min, V = 83.9-132.4 ml/kg).
      GS522 follows linear pharmacokinetics, with the area under the curve being
      proportional to the dose (Rsq = 0.9744). Highest radioactivity levels were
      detected in kidney, liver and blood (39.7, 15.7 and 15.3% dose/ respective
      organ). Less than 1% of the dose was detected in the heart, spleen and lungs, and
      >0.3% of the dose was found in the brain and eyes. The oligonucleotide associated
      radioactivity was uniformly distributed between the brain regions (left and right
      lobe and cerebellum). Six hours following the dose administration a statistically
      significant increase (p < 0.05) in radioactivity levels was observed in the
      brain, eyes, skin, liver, pancreas and vein. CONCLUSIONS: The pharmacokinetic and
      biodistribution profiles of GS522 following intravenous administration to rats at
      three doses were characterized. The oligonucleotide associated radioactivity was
      widely distributed in tissues. The amount of radioactivity sharply decreased with
      time in most tissues. Kidney, liver and muscle were the main sites of
      accumulation. The oligonucleotide associated radioactivity did not cross the
      blood brain barrier to an appreciable extent. In addition, a statistically
      significant increase (p < 0.05) in the radioactivity levels observed in select
      tissues suggested a re-uptake mechanism for intact oligonucleotide or its
      degradation products.

PMID- 9647358
TI  - Receptor occupancy in myocardium, adrenal cortex, and brain by TH-142177, a novel
      AT1 receptor antagonist in rats, in relation to its plasma concentration and
      hypotensive effect.
AB  - PURPOSE: To study the relationship between angiotensin II (AII) receptor
      occupancy ex vivo in tissues plasma concentration and hypotensive effect of a
      novel AII receptor antagonist, TH-142177 and losartan in rats. METHODS: At 2, 8
      and 24 hr after oral administration of TH-142177 and losartan in rats, AII
      receptors in myocardium, adrenal cortex and cerebral cortex were determined by
      radioligand binding assay using [125I]Sar1,Ile8-AII. Plasma concentrations of
      both drugs and metabolite in rats were also measured using validated HPLC assays.
      Further, systolic blood pressure (SBP) in conscious renal hypertensive rats
      treated orally with TH-142177 and losartan were measured by using a tail cuff
      plethysmographic method. RESULTS: Oral administration of TH-142177 (1.8 and 5.5
      micromol/kg) and losartan (6.5 and 21.7 micromol/kg) in rats brought about dose
      dependent decreases in [125I]Sar1,Ile8-AII binding sites (Bmax) in myocardium and
      adrenal cortex. The extent of receptor occupancy by both drugs in adrenal cortex
      was maximal at 2 hr later but that in myocardium at 8 hr later. Further, the
      receptor occupancy was more sustained in myocardium than adrenal cortex. The ex
      vivo binding affinity of TH-142177 for AII receptors in these tissues was roughly
      three times higher than that of losartan. Also, cerebral cortical [125I]Sar1,Ile8
      AII binding was significantly reduced by oral administration of losartan but not
      by TH-142177. The time course of AII receptor occupancy by both drugs in adrenal
      cortex appeared to be in parallel with that of their plasma concentrations, while
      the time course in myocardium correlated with that of their hypotensive effects
      rather than plasma concentrations. CONCLUSIONS: TH-142177 produced a relatively
      selective and sustained occupancy ex vivo of AII receptors in myocardium and
      adrenal cortex of rats with approximately three times greater potency than
      losartan. Its time course of myocardial receptor occupancy was in parallel with
      that of hypotensive effect rather than plasma concentration.

PMID- 9647359
TI  - Non-invasive assessment and control of ultrasound-mediated membrane
      permeabilization.
AB  - PURPOSE: Ultrasound has been shown to transiently permeabilize biological
      membranes, thereby facilitating delivery of large compounds such as proteins and
      DNA into cells and across tissues such as skin. In this study, we sought to
      quantitatively determine the dependence of cell membrane permeabilization on
      ultrasound parameters and to identify acoustic signals which correlate with
      observed membrane permeabilization. METHODS: Bovine red blood cells were exposed
      to ultrasound at 24 kHz over a range of controlled conditions. The degree of
      membrane permeabilization was measured by release of hemoglobin and was
      determined as a function of ultrasound parameters and measured acoustic signals.
      RESULTS: These studies showed that permeabilization increased with incident
      ultrasound pressure, increased with total exposure time above a threshold of
      approximately 100 msec, showed a weak dependence on pulse length with a small
      maximum at 3 msec, and did not depend on duty cycle under the conditions
      examined. Using measured acoustic spectra we found that red blood cell membrane
      permeabilization correlated best with the pressure measured at half the driving
      frequency (f/ 2 = 12 kHz) and its ultraharmonics, less strongly with the
      broadband noise pressure measured between peaks, and least strongly with pressure
      measured at the driving frequency and its higher harmonics. Permeabilization
      caused by ultrasound applied at any set of conditions tested in this study could
      be well predicted by the parameter tau x Pf/2, which characterizes the total
      cavitational exposure. CONCLUSIONS: This study provides a quantitative guide to
      designing ultrasound protocols useful for drug delivery. The acoustic
      measurements support the hypothesis that ultrasonic cavitation is the mechanism
      by which membranes are permeabilized. They also suggest that measurable acoustic
      signals can provide noninvasive, real-time feedback about membrane
      permeabilization and drug delivery.

PMID- 9647360
TI  - Mechanistic studies on effervescent-induced permeability enhancement.
AB  - PURPOSE: To determine the mechanism(s) by which effervescence induces penetration
      enhancement of a broad range of compounds ranging in size, structure, and other
      physiocochemical properties across rat and rabbit small intestinal epithelium.
      METHODS: Effervescent induced penetration enhancement was investigated in vitro
      by utilization of a modified Ussing chamber diffusion cell apparatus and in vivo
      by single-pass intestinal perfusion. RESULTS: Carbon dioxide (CO2) bubbling
      directly onto rabbit ileum epithelium induced an increase in drug permeability.
      Mechanistic studies indicated that effects due to CO2 bubble evolution, such as
      increased drug dissolution rates, mucus thinning/stripping, and pH buffer effects
      did not contribute to increases in drug flux. Cellular enzyme (5'-ND and LDH) and
      total protein release assays did not indicate cell membrane perturbation and/or
      damage. CO2 bubbling induced a reduction in transepithelial electrical resistance
      (TEER) indicating epithelial disruption due to a structural change of the
      paracellular pathway. This was further substantiated by a MW dependence on
      paracellular marker flux. In addition, tissue recovery was relatively rapid,
      approximately 20 min. CONCLUSIONS: CO2 bubbling directly onto the intestinal
      epithelium induced enhanced drug permeability due to an alteration of the
      paracellular pathway. This, in addition to fluid flow and membrane hydrophobicity
      concepts, may account for observed increases in drug flux.

PMID- 9647361
TI  - Triazene drug metabolites: part 15. Synthesis and plasma hydrolysis of anticancer
      triazenes containing amino acid carriers.
AB  - PURPOSE: The synthesis of chemically stable triazene prodrugs capable of
      hydrolysing under physiological conditions to liberate cytotoxic
      monomethyltriazene alkylating agents. METHODS: A series of 3-aminoacyl-1-aryl-3
      methyltriazenes was synthesised through reaction of 1-aryl-3-methyltriazenes with
      N-BOC protected amino acids using the DCC method of activation, followed by
      deprotection of the amino function using HCl in nitromethane. Half-lives for the
      hydrolysis of these compounds to the corresponding monomethyltriazenes at 37
      degrees C in isotonic phosphate buffer and in 80% human plasma containing 20%
      phosphate buffer were determined by HPLC. RESULTS: The aminoacyltriazene prodrugs
      hydrolyse in isotonic phosphate buffer with t1/2 values ranging from 26 to 619
      minutes. In human plasma, several decompose at the same rate as in phosphate
      buffer whereas those containing more lipophilic groups decompose more slowly. A
      beta-alanyl derivative was found to be more stable in phosphate buffer (t1/2 =
      180 minutes) than in plasma (t1/2 = 53 minutes). An N-acetylated alpha-alanyl
      derivative was found to be chemically stable in phosphate buffer (t1/2 = 10
      hours) but liberated the cytotoxic drug in t1/2 = 41 minutes in plasma,
      demonstrating its ability to act as a substrate for plasma enzymes. CONCLUSIONS:
      Aminoacyltriazenes are prodrugs of the antitumour monomethyltriazenes hydrolysing
      in human plasma with a range of reactivities. The acylation of the alpha-amino
      group seems to be an effective and simple means of reducing the chemical
      reactivity of the alpha-aminoacyl derivatives while retaining a rapid rate of
      enzymatic hydrolysis.

PMID- 9647362
TI  - LC-UV-electrospray-MS-MS mass spectrometry analysis of plant constituents
      inhibiting xanthine oxidase.
AB  - PURPOSE: A previous screening showed that Amyema scandensi [corrected] Danser
      (Loranthaceae) efficiently inhibited XOD. The aim of this study was to identify
      the compounds with anti-XOD properties. For this purpose, Electrospray Tandem
      Mass Spectrometry (ESI-MS-MS) coupled with UV and Diode Array LC techniques were
      employed. METHODS: Leaves were delipidized with petroleum ether and extracted
      with acetone:water 70:30, v:v. The extract was fractionated into the ethyl
      acetate and water soluble phases. Chemical investigation was performed following
      the bioactivity guided fractionation. Two fractions with anti-XOD activity were
      isolated by silica gel column chromatography of the ethyl acetate phase and
      analyzed by LC-UV-ESI-MS-MS. RESULTS: The compounds identified with authentic
      standards were: catechin, epicatechin, epicatechin-3-gallate, quercetin-3-O
      glucoside, quercetin-3-O-rhamnoside, and isorhamnetin-3-O-glucoside. Other
      constituents, only partially characterized, were a procyanidin dimer, a
      procyanidin trimer, three dimers epi/catechine-epi/catechine gallate and
      isorhamnetin-O-deoxyhexose. The anti-XOD activity was mainly due to galloyl
      containing oligomeric proanthocyanidins. CONCLUSIONS: The coupling of UV Diode
      Array-HPLC with ESI-MS-MS represents a versatile tool for the rapid
      characterization of compounds in complex mixtures, avoiding time-consuming
      previous isolation.

PMID- 9647363
TI  - Development of infrared imaging to measure thermogenesis in cell culture:
      thermogenic effects of uncoupling protein-2, troglitazone, and beta-adrenoceptor
      agonists.
AB  - PURPOSE: Although the effects of thermogenic agents in cell culture can be
      measured by direct microcalorimetry, only a few samples can be analyzed over
      several hours. In this report, we describe a robust non-invasive technique to
      measure real-time thermogenesis of cells cultured in microtiter plates using
      infrared thermography. METHODS: Yeast were transformed with uncoupling protein-2
      (UCP2) or exposed to carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP)
      or rotenone. Adipocytes were exposed to rotenone, FCCP, cycloheximide.
      troglitazone, or CL316243. Thermogenesis was measured using infrared
      thermography. RESULTS: Thermogenesis increased after exposing yeast to the
      mitochondrial uncoupler, FCCP, or transforming the cells with UCP2. Further,
      thermogenesis in adipocytes was stimulated by CL316243, a beta3-adrenoceptor
      agonist being developed to treat obesity. The protein synthesis inhibitor,
      cycloheximide, did not inhibit CL316243-mediated thermogenesis. In contrast, the
      mitochondrial proton transport inhibitor, rotenone, inhibited thermogenesis in
      yeast and adipocytes. Similarly, the antidiabetic agent, troglitazone, suppressed
      thermogenesis in adipocytes. Although increased UCP synthesis resulted in
      increased thermogenesis in yeast, UCP expression did not correlate with
      thermogenesis in adipocytes. CONCLUSIONS: The results, taken together with the
      high resolution (0.002 degrees C) and robustness (384-well format) of the
      approach, indicate infrared-imaging is a rapid and effective method for measuring
      thermogenesis in vitro.

PMID- 9647364
TI  - Intestinal absorption of ribavirin is preferentially mediated by the Na+
      nucleoside purine (N1) transporter.

PMID- 9647365
TI  - Absorption of propranolol in humans following oral, jejunal, and ileal
      administration.

PMID- 9647366
TI  - Endoscopic ultrasonography versus cholangiography for the diagnosis of
      choledocholithiasis.
AB  - BACKGROUND: Choledocholithiasis is a major source of morbidity among patients
      undergoing cholecystectomy for symptomatic gallstones. There is no consensus on
      the best approach to diagnosing bile duct stones. We compared the safety,
      accuracy, diagnostic yield, and cost of EUS- and ERCP-based approaches. METHODS:
      Sixty-four consecutive pre- and post-cholecystectomy patients referred for
      endoscopic retrograde cholangiopancreatography (ERCP) for suspected
      choledocholithiasis were prospectively evaluated in a blinded fashion. All were
      stratified into risk groups using predefined criteria. Endoscopic ultrasonography
      (EUS) and ERCP were sequentially performed by two endoscopists. RESULTS: The
      success rates of EUS and ERCP were 98% and 94%, respectively. The accuracy of EUS
      for diagnosing choledocholithiasis was 94%. EUS provided an additional or
      alternative diagnosis to bile duct stones in 21% of patients. The complication
      rate of EUS was significantly lower than diagnostic ERCP. An EUS-based strategy
      costs less than diagnostic ERCP in patients with low, moderate, or intermediate
      risk. CONCLUSIONS: EUS is comparably accurate, but safer and less costly than
      ERCP for evaluating patients with suspected choledocholithiasis. It is useful in
      patients with an increased risk of having common bile duct stones based on
      clinical criteria and those with contraindications for or prior unsuccessful
      ERCP. EUS may enable selective performance of ERCP and improve the cost
      effectiveness of diagnosing choledocholithiasis.

PMID- 9647367
TI  - Does endoscopy have a positive impact on quality of life in dyspepsia?
AB  - BACKGROUND: It is unclear whether normal endoscopy results in patients
      investigated for dyspepsia has therapeutic value. Therefore the aim of this study
      was to evaluate the effect of the endoscopy on quality of life and dyspeptic
      symptoms. METHODS: One hundred ninety-six symptomatic patients (85 men and 111
      women, mean age 42.9 years), who were receiving no treatment, were investigated
      before and 1 week after endoscopy with the use of a battery of validated
      questionnaires. RESULTS: Before endoscopy the health-related quality of life was
      compromised in comparison with a normal population, but 1 week after a negative
      endoscopy it is increased to a level which was close to the normal range despite
      no major change in symptoms. Physical activity and sleep scores improved
      significantly after endoscopy. CONCLUSION: The present results suggest that a
      negative endoscopy improves quality of life in the short-term in patients with
      dyspepsia, even though symptoms may persist.

PMID- 9647368
TI  - Placebo-controlled trial assessing the use of oral midazolam as a premedication
      to conscious sedation for pediatric endoscopy.
AB  - BACKGROUND: This study was performed to evaluate the effect of midazolam, as
      premedication before intravenous conscious sedation, on preprocedural,
      procedural, and post-procedural patient comfort and anxiety in children
      undergoing endoscopy. METHODS: A placebo-controlled, double-blind, randomized
      study was conducted in 123 children (age 7.75 +/- 4.46 years, 56% male) using
      oral midazolam (0.5 mg/kg, maximum 20 mg) as a premedication before insertion of
      an intravenous access device (i.v.) and upper endoscopy. Patients were evaluated
      with regard to changes in vital signs, level of sedation during i.v. placement,
      level of pre- and post-procedure conscious sedation, ease of separation from
      parents, ease and duration of procedure, recovery time, and amnesia to objects
      shown before i.v. placement and immediately before the start of the procedure.
      RESULTS: A significant difference was noted in the study group for the following
      parameters: level of sedation for i.v. placement (p < 0.0001), pre-procedural
      sedation (p < 0.001), ease of i.v. insertion (p < 0.003), ease of separation from
      parents (p = 0.022), and ease of the nursing personnel's ability to monitor the
      patient during the procedure (p = 0.0012). The patient's amnesia to an object
      shown immediately before beginning the endoscopy was increased (p < 0.001).
      Patients and parents were also more satisfied with the procedure process (p <
      0.05). No significant difference was noted with regard to the length or
      performance of the procedure or recovery time or in the dose of i.v. medication
      required for successful completion of the endoscopy. CONCLUSION: Oral midazolam
      is an effective and safe premedication for children undergoing upper endoscopy
      and should be used in all anxious children and in patients previously judged to
      be difficult to sedate.

PMID- 9647369
TI  - A prospective endoscopic study of scalloped folds and grooves in the mucosa of
      the duodenum as signs of villous atrophy.
AB  - BACKGROUND: Scalloping of the valvulae conniventes visible at endoscopy may
      predict the presence of villous atrophy. This prospective study was designed to
      discover how commonly duodenal mucosal scallops and grooves occurred and to
      delineate their relationship to villous atrophy. METHODS: All patients undergoing
      upper gastrointestinal endoscopy by a single observer over 5 years were included.
      After inspection of the duodenal mucosa, biopsy samples were taken from those in
      whom the mucosa was abnormal (n = 26) and from those in whom it was not, but
      where biopsy was indicated (n = 100). RESULTS: None of the 100 endoscopically
      normal controls had subtotal villous atrophy: 94 had normal histology, 2 had non
      atrophic change, and 4 had partial villous atrophy; 14 of the 26 individuals
      (54%) with abnormal duodena had subtotal villous atrophy, 7 having both scallops
      and grooves. Four had scallops alone, and three had grooves only. All patients
      with both scallops and grooves had subtotal villous atrophy (100%), the positive
      predictive value of which was 36% for scallops alone and 38% for grooves alone.
      CONCLUSIONS: Scallops and grooves together indicate that subtotal villous atrophy
      is very likely histologically, even when that diagnosis has not been suspected. A
      normal duodenum excludes it.

PMID- 9647370
TI  - Endoscopic resection of small duodenal carcinoid tumors with strip biopsy
      technique.
AB  - BACKGROUND: Most cases of duodenal carcinoid have conventionally been treated by
      surgical resection. The aim of our study was to explore the feasibility of
      endoscopic resection in small duodenal carcinoids. METHODS: The study population
      consisted of seven patients with small duodenal carcinoids. The diagnosis was
      confirmed by preoperative biopsies. The depth of tumor invasion was evaluated by
      endosonography. RESULTS: The carcinoid was detected by endosonography in all
      cases. Size ranged ultrasonographically from 1.5 mm to 7 mm. Tumor invasion was
      confined to the submucosa in all patients. Endoscopic resection was performed
      with the strip biopsy technique using a two-channel endoscope. In six patients,
      the specimens were resected without severe complications. Five of them were
      confirmed histologically to be typical carcinoids. In one patient, carcinoid was
      not detected histologically in the specimen. In the remaining patient, a
      perforation occurred. However, the huge ulcer was managed conservatively. Follow
      up endoscopy revealed no evidence of recurrent or residual tumor in any patient.
      CONCLUSION: Small duodenal carcinoids confined to the submucosa can be resected
      endoscopically and preoperative endosonography is necessary for the determination
      of endoscopic resectability.

PMID- 9647371
TI  - Dilated common channel syndrome: endoscopic diagnosis, treatment, and
      relationship to choledochocele formation.
AB  - BACKGROUND: Choledochoceles (type III biliary cysts) are cystic dilations of the
      terminal common bile duct or common pancreatobiliary channel. Although no size
      criteria have been defined, it is generally assumed these must be large. However,
      we describe patients who do not meet the perceived size criteria for
      choledochoceles, but who nonetheless have a dilated common pancreatobiliary
      channel. METHODS: We reviewed the presenting symptoms, endoscopic and
      radiographic findings, and response to endoscopic therapy of patients meeting our
      criteria for the dilated common channel syndrome. RESULTS: Of 2847 patients
      undergoing ERCP, 100 (3.5%) had the dilated common channel syndrome. Common
      presenting symptoms and signs included abdominal pain in 97%, abnormal liver
      function test(s) in 66%, and a history of acute or recurrent pancreatitis in 46%.
      A bulge was visible above the papilla in 88%, with a dilated common bile duct in
      54% and a dilated pancreatic duct in 28%. After endoscopic unroofing of the
      common channel, 77% had complete and long-lasting resolution of symptoms, 18% had
      partial or transient improvement, and 5% had no change. CONCLUSIONS: Although
      classic choledochoceles are rare, a lesser degree of dilation of the common
      channel is more frequent than generally appreciated. We postulate that this
      finding represents an "incomplete," acquired form of choledochocele, possibly
      caused by underlying papillary stenosis. Whatever the etiology and appropriate
      term, the presence of a dilated common channel predicts a high rate of clinical
      response to endoscopic therapy.

PMID- 9647372
TI  - Relative contribution of Ki-ras gene analysis and brush cytology during ERCP for
      the diagnosis of biliary and pancreatic diseases.
AB  - BACKGROUND: Ki-ras mutation analysis from material collected during ERCP has been
      claimed to improve the diagnosis of pancreatic and bile duct carcinomas as
      compared with conventional cytology. Our aim was to study the relative
      contribution of both Ki-ras analysis and brush cytology in patients with a
      significant stricture at ERCP. METHODS: Brushings were collected in duplicate for
      both analyses in 142 patients in whom a definitive diagnosis was obtained by
      histology or a minimal follow-up of 6 months. RESULTS: For pancreatic strictures,
      sensitivity, specificity, and accuracy of Ki-ras analysis vs. cytology in
      detecting malignancy were 81% vs. 66%, 72% vs. 100%, and 70% vs. 74%,
      respectively. For biliary strictures, they were 25% vs. 42%, 100% vs. 100%, and
      35% vs. 43%, respectively. The combination of the two methods only marginally
      increased their sensitivity and accuracy in both types of strictures. CONCLUSION:
      Ki-ras analysis is a sensitive method for diagnosing pancreatic but not biliary
      carcinoma. However, its specificity is lowered by a high frequency of Ki-ras
      mutations in patients with chronic pancreatitis (25%) who did not manifest cancer
      development within a 6-month follow-up period. In pancreatic duct strictures,
      brush cytology appears to be more specific in detecting malignancy; specificity
      for Ki-ras and cytology are equivalent for the diagnosis of malignant bile duct
      strictures. Therefore, making a clinical decision on the sole basis of Ki-ras
      analysis is probably not justified in the majority of the cases.

PMID- 9647373
TI  - Endoscopic retrieval of proximally migrated biliary and pancreatic stents:
      experience of a large referral center.
AB  - BACKGROUND: Proximal migration of a biliary or pancreatic stent is an infrequent
      event but its management can be technically challenging. METHODS: Review of all
      cases of proximally migrated biliary and pancreatic stents over a 10-year period
      at a referral pancreatic-biliary center. Data abstracted from patient records
      included indication for stenting, method of presentation, success of attempt, and
      method used. Successful methods were determined by reviewing procedure reports.
      Follow-up was attempted in all patients in whom stent retrieval had failed.
      RESULTS: Thirty-three proximally migrated bile duct stents, and 26 proximally
      migrated pancreatic duct stents were identified. Most of the patients were
      without symptoms. Eighty-five percent of common bile duct stents and 80% of
      pancreatic duct stents were successfully extracted endoscopically. Seventy-one
      percent (34 of 48) were retrieved with a basket or balloon. Of the stents not
      retrieved, two patients did not return for repeat ERCP, three patients with
      malignant common bile duct strictures were managed with placement of a second
      stent, three patients with pancreatic duct stents have remained without symptoms
      with no further retrieval attempts, and three patients with proximally migrated
      pancreatic duct stents required surgery because of pain and failure of multiple
      endoscopic retrieval attempts. CONCLUSION: Over 80% of proximally migrated bile
      duct and pancreatic duct stents may be extracted endoscopically. Few patients
      will require surgery.

PMID- 9647374
TI  - ERCP in the management of pediatric pancreatitis.
AB  - BACKGROUND: Although ERCP is commonly performed in children, the effect of
      findings at ERCP on the subsequent management of pediatric pancreatitis is
      unknown. METHODS: We retrospectively reviewed charts to determine the impact of
      ERCP on the management of recurrent acute or chronic pancreatitis in 17
      consecutive children (3 boys and 14 girls, 3 to 16 years, mean 11.2 years) with
      recurrent acute (n = 13) or chronic pancreatitis (n = 4) who underwent ERCP.
      Radiographs were reviewed in a blinded manner, and the effect of ERCP findings on
      subsequent management was determined. RESULTS: In 16 of 17 patients (94%), the
      pancreatic duct was successfully visualized. Of the 16 studies, 9 (56%) had
      abnormal findings. A change in therapy occurred in all 9 patients as a result of
      the findings at ERCP. Of the 7 patients with a prior abnormal CT or ultrasound, 5
      (71%) had an abnormal ERCP, all resulting in a change in therapy. Three of the 9
      patients (33%) without radiographic abnormalities had an abnormal ERCP that, in
      each case, resulted in a change in therapy. Overall, findings at ERCP altered
      therapy in 52% of pediatric patients studied with recurrent acute or chronic
      pancreatitis. A prior abnormal CT had a high predictive value with respect to
      ERCP resulting in a change in management (83%). CONCLUSIONS: ERCP is useful in
      the management of pediatric recurrent acute or chronic pancreatitis;
      abnormalities are found at a rate similar to those found in adults.

PMID- 9647375
TI  - Ineffective use of a detachable snare for colonoscopic polypectomy of large
      polyps.
AB  - BACKGROUND: Colonoscopic polypectomy of large polyps may be associated with
      complications such as bleeding. Use of a detachable snare may reduce the risk of
      bleeding. We describe several instances in which the use of such a device proved
      to be ineffective. METHODS: A detachable snare was used for colonoscopic
      polypectomy of large polyps in 18 patients (20 polyps), also applied at the
      residual stalk after conventional polypectomy in 5 patients (5 polyps), and
      evaluated retrospectively. RESULTS: Sixteen of the 20 polyps were pedunculated,
      and 4 were semi-pedunculated. In 3 of the 4 semi-pedunculated lesions, the loop
      slipped off after polypectomy because the lesions were cut close to the site of
      encirclement. Bleeding occurred in 4 cases because of transection by the loop of
      a thin stalk (4 mm) before polypectomy (1), slipping of the loop in a semi
      pedunculated lesion (1), or insufficient tightening of the loop (2). After
      conventional polypectomy, we could not effectively snare the residual stalk
      because of flattening in 3 of the 5 lesions. CONCLUSIONS: Use of the detachable
      snare for polypectomy of thin stalked or semi-pedunculated lesions may result in
      technical failure of this technique. The stalk should be fully encircled with the
      snare before polypectomy. The detachable snare is difficult to apply at the
      residual stalk after conventional polypectomy.

PMID- 9647376
TI  - Current laparoscopic gastrointestinal surgery.

PMID- 9647377
TI  - Acetic acid improves identification of remnant islands of Barrett's epithelium
      after endoscopic therapy.
AB  - BACKGROUND: Instillation of acetic acid onto the uterine cervix at colposcopy has
      been used for many years to highlight dysplastic areas and thereby enhance the
      ability to obtain targeted biopsy specimens. As part of an ongoing trial of
      multipolar electrocoagulation for Barrett's esophagus, we sought to develop a
      simple technique to identify small islands of residual specialized columnar
      epithelium after treatment. METHODS: In 21 consecutive patients, 5 to 10 mL of
      1.5% acetic acid was sprayed onto the distal esophagus using a spray catheter,
      followed immediately by spraying 50 mL of tap water. RESULTS: Initially, a
      whitish coloration developed in both esophageal and gastric epithelia. After 2 to
      3 minutes, the esophageal squamous mucosa remained white but the columnar
      epithelium became reddish. Remnant islands of Barrett's epithelium were outlined
      by a white rim. CONCLUSION: Acetic acid instillation enhances the ability to
      detect small or indistinguishable remnant islands of columnar epithelium after
      endoscopic treatment of Barrett's esophagus. This method is safe, rapid, and
      inexpensive.

PMID- 9647378
TI  - High-resolution cross-sectional imaging of the gastrointestinal tract using
      optical coherence tomography: preliminary results.
AB  - BACKGROUND: Optical coherence tomography (OCT) is a novel technique for
      noninvasive cross-sectional imaging with high spatial resolution (10 to 20
      microm). OCT is similar to B-mode ultrasound except that it uses infrared light
      rather than ultrasound. We studied OCT imaging of the gastrointestinal (GI) tract
      in vitro to analyze the potential of this technique for endoscopic applications.
      METHODS: Human gastrointestinal tissues harvested from surgical resection and
      autopsy specimens were used. Specimens were imaged within 5 hours of resection or
      snap frozen in liquid nitrogen. After imaging, OCT scan locations were carefully
      marked using dye microinjections, fixed, and prepared for routine histologic
      processing. OCT images were then compared and correlated with the histologic
      sections. RESULTS: OCT images demonstrated clear delineation of the mucosa and
      submucosa in most specimens. Furthermore, microscopic structures such as crypts,
      blood vessels, or esophageal glands in the submucosa and lymphatic nodules were
      observed. CONCLUSIONS: The resolution of OCT images of GI wall is sufficient to
      delineate the microscopic structure of the mucosa and submucosa. Potentially, OCT
      would allow in vivo imaging at endoscopy of the microstructure of the mucosa and
      submucosa. This would be particularly useful in the detection and staging of
      small lesions such as early stage cancers.

PMID- 9647379
TI  - Farewell to bacteremia caused by endoscopic injection--effectiveness of a new
      injection catheter with a covered tip.
AB  - BACKGROUND: Endoscopic injection has recently been reported as effective for
      several treatments. Because the common channel (suction and biopsy) is usually
      contaminated with aspirated gastrointestinal juice containing bacteria, often the
      tip of the injector needle is also. We report a new catheter needle with a
      covered tip designed to prevent bacteremia from endoscopic injection. METHODS:
      The new covered needle catheter (Clisco needle) has a 23-gauge retractable needle
      with a 3 mm extrusion in one lumen. Its distal tip is covered with rubber,
      blocking infiltration of contaminated gut juice. Ten of these catheters and 10
      other disposable needles were inserted through the colonoscope's biopsy channel
      for 10 patients. Needle tips were cut off after extrusion, and bacteria cultured
      were counted by standard plate count method. RESULTS: All cultures from ordinary
      needles grew Escherichia coli, whereas only 3 new needles grew E. coli. Average
      counts of bacteria cultured from these 3 catheters and 10 disposable needles were
      1-250 and 90-6.1 x 10(6), respectively. The difference was highly significant (p
      < 0.0001). CONCLUSIONS: This new covered needle catheter reduces contaminating
      bacteria in patients who require endoscopic injection and may prevent bacteremia
      without antibiotic prophylaxis.

PMID- 9647380
TI  - Alendronate-associated esophagitis: endoscopic and pathologic features.

PMID- 9647381
TI  - Esophageal granular cell tumor treated by endoscopic mucosal resection using a
      ligating device.

PMID- 9647382
TI  - Airway complications of esophageal self-expandable metallic stent.

PMID- 9647383
TI  - Spontaneous communication of a liver cyst with the bile ducts diagnosed by ERCP.

PMID- 9647384
TI  - A case of pyogenic granuloma in the duodenum: successful treatment by endoscopic
      snare polypectomy.

PMID- 9647385
TI  - Pneumoperitoneum complicating ERCP performed immediately after EUS-guided fine
      needle aspiration.

PMID- 9647386
TI  - Biliary stent migration with colonic diverticular perforation.

PMID- 9647387
TI  - Pancreatic acinar metaplasia in an inlet patch.

PMID- 9647388
TI  - Drug-induced esophageal damage: diseases of medical progress.

PMID- 9647389
TI  - The American Society for Gastrointestinal Endoscopy at the turn of the century
      and beyond.

PMID- 9647390
TI  - Emergency endoscopy in upper gastrointestinal bleeding at a second level unit:
      clinical results and quality assurance (QA), three year experience.

PMID- 9647391
TI  - Increased serum trypsinogen 2 and trypsin 2-1 antitrypsin complex values identify
      endoscopic retrograde cholangiopancreatography (ERCP)-induced pancreatitis with
      high accuracy.

PMID- 9647392
TI  - Assessment of residual gastric volume and thirst in patients who drink before
      gastroscopy.

PMID- 9647393
TI  - Endoscopic education in the Scandinavian countries: current status and a call for
      standards.

PMID- 9647394
TI  - Gastrointestinal endoscopy--a Canadian perspective.

PMID- 9647395
TI  - Comment--endoscopic quality and control.

PMID- 9647396
TI  - Sigmoido-anal intussusception presenting as rectal prolapse: role of endoscopic
      diagnosis.

PMID- 9647397
TI  - Role of percutaneous transhepatic cholangioscopy in biliary papillomatosis: can
      it change treatment modality?

PMID- 9647398
TI  - Post-cholecystectomy bile leaks and their management.

PMID- 9647399
TI  - "Unexpected" gastric ecchymosis.

PMID- 9647400
TI  - Technology Assessment Status Evaluation: botulinum toxin therapy in
      gastrointestinal endoscopy. November, 1996. ASGE. American Society for
      Gastrointestinal Endoscopy.

PMID- 9647401
TI  - Technology Assessment Status Evaluation--update: endoscopic band ligation.
      November, 1996. ASGE. American Society for Gastrointestinal Endoscopy.

PMID- 9647402
TI  - Technology Assessment Status Evaluation: tissue sampling during endosonography.
      February 1997. ASGE. American Society for Gastrointestinal Endoscopy.

PMID- 9647403
TI  - Technology Assessment Status Evaluation: guidewires in gastrointestinal
      endoscopy. February, 1997. ASGE. American Society for Gastrointestinal Endoscopy.

PMID- 9647404
TI  - Technology Assessment Status Evaluation update: transvenous intrahepatic
      portosystemic shunt (TIPS). April, 1997. ASGE. American Society for
      Gastrointestinal Endoscopy.

PMID- 9647405
TI  - Technology Assessment Status Evaluation: stents for gastrointestinal strictures.
      May, 1997. ASGE. American Society for Gastrointestinal Endoscopy.

PMID- 9647406
TI  - The new heparins.

PMID- 9647407
TI  - Novel anticoagulants based on direct inhibition of thrombin and factor Xa.

PMID- 9647408
TI  - Novel anticoagulants based on inhibition of the factor VIIa/tissue factor
      pathway.

PMID- 9647409
TI  - Novel antithrombotics based on modulation of the protein C pathway.

PMID- 9647410
TI  - Novel approaches to thrombolysis based on modulation of endogenous fibrinolysis.

PMID- 9647411
TI  - Coronary vasoreactivity to ergonovine after angioplasty: difference between the
      infarct-related coronary artery and the noninfarct-related coronary artery.
AB  - BACKGROUND: The vasoreactivity after direct percutaneous transluminal coronary
      angioplasty (PTCA) in patients with previous myocardial infarction remains
      unknown. We examined the constrictor response to ergonovine of the infarct
      related coronary artery in comparison with that of noninfarct-related coronary
      artery after angioplasty. METHODS: Ergonovine was administered intravenously to
      17 patients with previous myocardial infarction (group I) and to 21 patients with
      stable angina (group II) 1 year after PTCA. The effects of ergonovine on lumen
      diameter were analysed quantitatively at the PTCA segment, nonPTCA segment
      (proximal to the PTCA segment), and nonPTCA artery. RESULTS: The ergonovine
      induced decrease in minimal lumen diameter at the PTCA segment was significant in
      group I (decrease from 2.12 +/- 0.56 to 1.39 +/- 0.74 mm, P < 0.01), but not in
      group II (decrease from 1.60 +/- 0.35 to 1.43 +/- 0.33 mm, NS). Patients in group
      I showed a constrictor response at the nonPTCA artery (decrease in diameter from
      2.54 +/- 0.90 to 1.94 +/- 0.77 mm, P < 0.01), and a tendency to constrict at the
      nonPTCA segment (2.56 +/- 0.67 to 2.11 +/- 0.66 mm, P = 0.06), whereas those in
      group II showed no significant constrictor response to ergonovine at any of the
      three segments examined. The changes in diameter at the three segments in
      patients in group I were significantly greater than those in group II (all P <
      0.01). Subtotal coronary spasm at the PTCA segment was provoked only in three
      patients in group I (18%). CONCLUSIONS: The constrictor response to ergonovine of
      the infarct-related coronary artery was enhanced compared with that of the
      noninfarct-related coronary artery. This difference in coronary vasoreactivity at
      the angioplasty segment may be due to previous hypersensitivity of the smooth
      muscle.

PMID- 9647412
TI  - Whole blood viscosity and haematocrit are associated with internal carotid
      atherosclerosis in men.
AB  - BACKGROUND: Alterations in blood viscosity and haematocrit have been described in
      patients with coronary and cerebrovascular diseases. The results have not been
      conclusive, as modifications of these parameters are often associated with the
      presence of coronary heart disease (CHD) risk factors. The aim of this study was
      to verify whether blood viscosity and haematocrit are increased in patients with
      carotid atherosclerosis, independently of the presence of CHD risk factors.
      METHODS: Male patients with internal carotid atherosclerosis (ICA+, n = 28) were
      selected from participants in a cardiovascular disease prevention campaign.
      Controls (ICA-, n = 28), also participating in the prevention campaign, were
      matched for age and all the classical CHD risk factors. Plasma lipids, glucose
      and fibrinogen were determined by routine methods. Cigarette smoking and current
      drug therapy was established by questionnaire. Whole blood viscosity was measured
      at shear rates of 450 and 225/s, using a cone-plate viscometer. Echo-Doppler of
      carotid arteries was performed with an ATL Ultramark 9 HDI using a 5-10 MHz
      multifrequency probe. RESULTS: Blood pressure, plasma lipids, glucose, body mass
      index, fibrinogen and plasma viscosity were similar in the two groups. ICA+
      patients, compared with the ICA- group, had significantly greater values of blood
      viscosity (4.52 +/- 0.37 cP compared with 4.18 +/- 0.45 cP, P < 0.005
      respectively; shear rate 450/s) and haematocrit (48.57 +/- 3.19% compared with
      45.57 +/- 4.81%, P < 0.008 respectively). CONCLUSIONS: Our findings demonstrate
      that blood viscosity and haematocrit are increased in men with internal carotid
      atherosclerosis, independently of the presence of risk factors for
      atherosclerosis.

PMID- 9647413
TI  - Failure to confirm ferritin and caeruloplasmin as risk factors for the
      angiographic extent of coronary arteriosclerosis.
AB  - BACKGROUND: It has been suggested that iron overload, as assessed by increased
      serum ferritin concentration, may be a risk factor for coronary artery disease
      (CAD). Recent studies have reported conflicting data on the role of ferritin and
      other parameters of oxidative metabolism in CAD. OBJECTIVE: The aim of this study
      was to assess the relation between the extent of CAD and parameters of oxidation.
      METHODS: We studied 275 patients (208 men aged 55.1 +/- 9.6 years and 67 women
      aged 54.6 +/- 10.0 years) who underwent coronary angiography or percutaneous
      transluminal coronary angioplasty for the first time. The parameters assessed
      were: iron, ferritin, transferrin, copper, caeruloplasmin and lipid. Cinefilms
      were assessed by the use of three scores: (1) Vessel score: 0-3 points; 1 point
      for each of the three main coronary arteries with a stenosis >70%. (2) Stenosis
      score: 0-32 points; the coronary artery tree was divided into eight segments that
      were scored 1-4 points per segment with respect to the maximal degree of
      stenosis. (3) Extent score: 0-100 points; extent of diffuse coronary lesions in
      each segment in relation to the length of the vessel. Multiple regression
      analyses were used to evaluate the results. RESULTS: Total cholesterol and low
      density lipoprotein cholesterol (P < 0.001) in women, low-density lipoprotein
      cholesterol (P < 0.05) in men, and patient age showed a significant correlation
      with all three scores, but none of the parameters of oxidative metabolism (iron,
      transferrin, ferritin, copper, caeruloplasmin) correlated significantly with any
      of the three scores. CONCLUSION: This study demonstrated a correlation between
      lipoproteins and the angiographic extent of CAD, but did not confirm a role for
      serum ferritin and other oxidative parameters as risk factors for the extent of
      CAD.

PMID- 9647414
TI  - Relation between successful late coronary angioplasty of an occluded, infarction
      related artery and lower prevalence of ventricular late potentials.
AB  - BACKGROUND: The effect of mechanical reperfusion of the infarction-related artery
      on ventricular late potentials (VLP) continues to be debated. OBJECTIVE: To
      assess the influence of successful late coronary angioplasty on the prevalence of
      VLP after acute myocardial infarction (AMI). METHODS: We studied 113 consecutive
      patients (97 men, 16 women, mean age 57 +/- 10.8 years) in whom the infarction
      related artery was occluded (thrombolysis in myocardial infarction score 0 or 1)
      at the time of the initial coronary arteriography 10.9 +/- 6.4 days after a first
      AMI. Successful late angioplasty of the infarcted artery was performed in 55
      patients a mean of 11.5 +/- 7.2 days after AMI. The remaining 58 patients
      received a conservative treatment. Signal-averaged electrocardiograms (SAECGs)
      were recorded 25 +/- 10.2 days after AMI. Multivariate analysis was undertaken to
      assess the influence of late coronary angioplasty with respect to age, sex,
      infarction site, angiographic ejection fraction, extent of diseased coronary
      arteries, thrombolysis and time of recording the SAECG. RESULTS: The overall
      prevalence of VLP was 27%. It was greater in patients without than in those with
      angioplasty (40% compared with 15%, P = 0.017). Multivariate analysis
      demonstrated that successful angioplasty (odds ratio 3.2; P = 0.019) and ejection
      fraction >0.4 (odds ratio 5.1; P = 0.0051) were the strongest independent
      predictors of an absence of VLP. 'Non-inferior' myocardial infarction was also
      correlated with the absence of VLP (odds ratio 2.6), but with borderline
      significance (P = 0.053). CONCLUSION: When performed in an occluded, infarction
      related artery, successful late coronary angioplasty contributes to a significant
      decrease in the prevalence of VLP.

PMID- 9647415
TI  - Novel technetium-99m-labeled platelet GPIIb/IIIa receptor antagonists as
      potential imaging agents for venous and arterial thrombosis.
AB  - OBJECTIVES: Either venous or arterial thrombosis is a potentially life
      threatening event and existing diagnostic modalities are inadequate to diagnose
      and to determine the morphology of the evolving thrombus. Thus development of a
      noninvasive imaging agent that can detect clot location remains a critical and
      unmet need in nuclear diagnostic medicine. The present study was undertaken to
      determine the potential of platelet GPIIb/IIIa receptors compared with direct
      thrombin inhibitors, in the detection of venous and arterial clots. METHODS:
      Initially, the validity of exploiting the degree and extent of specific uptake
      and retention of a potent GPIIb/IIIa receptor antagonist in venous and in
      arterial thrombus was confirmed in vitro in artificially created arterial- or
      venous-type clots, using the radiolabeled antagonist, 3H-DMP728. This was
      followed by comparing the in-vivo clot/blood distribution of various technetium
      99m (99mTc)-labeled, DMP728-derived, GPIIb/IIIa receptor antagonists and of
      thrombin inhibitors, over time, in mixed arterial/venous or venous clots in
      arteriovenous shunt and in venous clot models in dogs. In addition, we performed
      noninvasive single-photon emission tomographic imaging of the venous clot in a
      deep vein thrombosis model in dogs. RESULTS: Our data confirmed that potency for
      the platelet GPIIb/IIIa receptors was maintained after radiolabeling of the
      parent active GPIIb/IIIa receptor antagonists. DMP728 demonstrated a relatively
      greater affinity for activated than for unactivated human platelets, which might
      be essential for attaining an optimal thrombus/blood (target/background)
      distribution ratio and the optimal detection of small clots (i.e. greater
      sensitivity). CONCLUSIONS: These data suggest a potential utility of 99mTc
      GPIIb/IIIa receptor antagonists, but not of direct thrombin inhibitors, in the
      diagnosis of venous clots in deep vein thrombosis, pulmonary embolism and
      arterial thromboembolic disorders including stroke and coronary and peripheral
      artery thrombotic disorders.

PMID- 9647417
TI  - Bibliography of current world literature.

PMID- 9647418
TI  - Couples relapse prevention sessions after behavioral marital therapy for male
      alcoholics: outcomes during the three years after starting treatment.
AB  - OBJECTIVE: This article provides a complete report of outcome data from a study
      of behavioral marital therapy (BMT) with and without additional couples relapse
      prevention (RP) sessions. (See J. Stud. Alcohol 54: 652-666, 1993, for an earlier
      partial report.) METHOD: Fifty-nine couples with an alcoholic husband, after
      receiving weekly BMT couples sessions for 5-6 months, were assigned randomly to
      get or not get 15 additional couples relapse prevention (RP) sessions over the
      next 12 months. Outcome measures were collected before and after BMT and at
      quarterly intervals for the 30 months after BMT. RESULTS: BMT-plus-RP produced
      more days abstinent and greater use of the Antabuse Contract than BMT-only; and
      these superior drinking outcomes for BMT-plus-RP lasted through 18-month follow
      up (i.e., 6 months after the end of RP). BMT-plus-RP had better wives' marital
      adjustment than BMT-only throughout the 30 months of follow-up, with the
      superiority of BMT-plus-RP over BMT-only being greatest for wives with poorer
      pretreatment marital adjustment during the later months of follow-up. BMT-plus-RP
      also maintained their improved marriages longer (through 24-month follow-up) than
      BMT-only (through 12-month follow-up). Irrespective of treatment condition, more
      use of BMT-targeted marital behaviors (e.g., shared recreational activities,
      constructive communication) was associated with better marital and drinking
      outcomes throughout the 30-month follow-up period whereas more use of the
      Antabuse contract was associated with better marital and drinking outcomes
      through 12-month follow-up. Alcoholics with more severe marital problems had more
      abstinent days and maintained relatively stable levels of abstinence if they
      received BMT-plus-RP, while their counterparts who received BMT-only had fewer
      abstinent days and showed a steep decline in abstinent days during the 30 months
      of follow-up. Furthermore, alcoholics with more severe alcohol problems used the
      Antabuse contract more and showed a less steep decline in use of the Antabuse
      contract in the 30 months of follow-up if they received BMT-plus-RP than if they
      received BMT-only. CONCLUSIONS: For the entire sample, BMT-plus-RP produced
      better marital outcomes throughout the 30 months of follow-up and better drinking
      outcomes during and for the 6 months following RP sessions, relative to BMT-only
      outcomes. For alcoholics with more severe marital and drinking problems, BMT-plus
      RP produced better drinking outcomes than BMT-only throughout the 30-month follow
      up period.

PMID- 9647416
TI  - Structural, biochemical and functional effects of distending pressure in the
      human saphenous vein: implications for bypass grafting.
AB  - BACKGROUND: Distension of the saphenous vein before and after coronary artery
      bypass grafting results in damage to mechanisms that regulate vascular tone. We
      have investigated the relationship between the magnitude of distending pressure
      and the degree of structural, biochemical and functional damage to the vessel
      wall. METHODS: Vessel segments that had been distended to either 100 or 300 mmHg
      were set up in isolated organ baths and the function of the smooth muscle and
      endothelial cells examined. All segments examined were then fixed for assessment
      of structural damage by scanning electron microscopy and for immunocytochemical
      localisation of endothelial nitric oxide synthase. RESULTS: Segments of saphenous
      vein distended to 100 mmHg retained their responsiveness to KCl (90 mmol/l) and
      phenylephrine (10(-6) mol/l), but those pressurised to 300 mmHg had significantly
      reduced responses to both agents. There was also a significant reduction in
      response to the endothelium-dependent dilators, acetylcholine (10(-10)-10(-6)
      mol/l) and bradykinin (10(-10)-10(-6) mol/l) in those segments distended to 300
      mmHg. Quantitative studies of structural endothelial damage showed a significant
      loss of endothelium at 300 mmHg distension pressure. Remaining endothelial cells
      retained strong positive staining for endothelial nitric oxide synthase. By
      electron microscopic examination, those vessels distended to 100 mmHg showed
      lifting and rounding of individual cells, whereas segments distended to 300 mmHg
      revealed major areas of denuded endothelium. CONCLUSIONS: Distension of saphenous
      veins to pressures equivalent to those in the systemic circulation result in
      structural and biochemical changes in the endothelium that are not paralleled by
      immediate functional vasomotor changes.

PMID- 9647419
TI  - Evaluating substance abuse treatment process models: I. Changes on proximal
      outcome variables during 12-step and cognitive-behavioral treatment.
AB  - OBJECTIVE: This article provides data on the early linkages in the treatment
      process chains that are thought to underlie two prevalent approaches to substance
      abuse treatment-traditional 12-step treatment and cognitive-behavioral treatment.
      The focus is on the during-treatment changes on "proximal outcomes" that,
      according to the treatment theory underlying each modality, patients are supposed
      to undergo or achieve in order to experience a positive "ultimate outcome."
      METHOD: In all, 3,228 men receiving treatment in 15 Department of Veterans
      Affairs substance abuse treatment programs were assessed at treatment entry and
      at or near discharge from inpatient programs that had desired lengths of stay of
      21-28 days. RESULTS: Between intake and discharge, patients in 12-step programs
      improved more than did C-B patients on proximal outcome variables assumed to be
      specific to 12-step treatment (e.g., attending 12-step meetings, taking steps),
      whereas patients in cognitive-behavioral programs made no greater change (and in
      a few cases, less change) than did 12-step patients on proximal outcome variables
      assumed to underlie cognitive-behavioral treatment (e.g., self-efficacy, coping
      skills). CONCLUSIONS: These findings suggest that the proximal outcomes thought
      to be specific to cognitive-behavioral treatment are actually general proximal
      outcomes of both 12-step and cognitive-behavioral treatment.

PMID- 9647420
TI  - Reflecting adult drinking culture: prevalence of alcohol use and drinking
      situations among Japanese junior high school students in Japan.
AB  - OBJECTIVE: To estimate the prevalence of Japanese adolescents' alcohol use in
      Japan and the situations surrounding their drinking. METHOD: A general population
      self-administered questionnaire survey was conducted with a sample of 5,240
      Japanese junior high school students obtained from 12 representative schools of
      the Chiba Prefecture in Japan. RESULTS: Almost 80% of the boys and 75% of the
      girls reported having consumed an alcoholic beverage on at least one occasion.
      Consumption occurred most frequently on a ceremonial occasion (52.4%), followed
      by drinking with family (39.0%), with peers (20.6%), after a bath (9.7%) and at
      ritual parties among friends (9.3%). In this sample, a greater percentage of
      students in a higher grade reported a drinking occasion after a bath, at parties
      among friends, or with peers. However, this trend was not observed for drinking
      on ceremonial occasions or with family in the evening. A gender difference was
      observed for the prevalence of drinking after a bath. A majority of students
      agreed with the statement that minors' use of alcohol was "acceptable depending
      on the situation." This was in sharp contrast with their perception of cigarette
      smoking and solvent use (16.3% and 3.8%, respectively, endorsing the same
      statement). CONCLUSIONS: By sometime in their first year of junior high school
      (when most students are age 12 years), more than 75% of Japanese adolescents have
      tried alcohol. Prevalence rates and trends across grades are different depending
      on the occasions of drinking. The findings on situational drinking among
      adolescents of this age group appear to reflect that assimilation into Japanese
      drinking culture takes place early on in family or traditional settings.

PMID- 9647421
TI  - Paternal alcoholism, paternal absence and the development of problem behaviors in
      boys from age six to twelve years.
AB  - OBJECTIVE: The purpose of this study was to examine the association between
      paternal alcoholism, paternal absence, and the development and stability of
      behavioral problems in boys, from kindergarten to the end of elementary school.
      METHOD: A sample of 642 boys originating from low socioeconomic status (SES)
      families was used. Paternal alcoholism was established using the Short Michigan
      Alcohol Screening Test. Behavioral problems (opposition, hyperactivity,
      inattention, physical aggression and anxiety) were assessed by teachers' reports
      when the boys were 6 and 12 years old. Four groups of boys were created on the
      basis of paternal alcoholism (nonalcoholic, alcoholic) and family structure
      (intact families, nonintact/father-absent families). RESULTS: Consistent with
      personality theories of alcoholism, results showed that a propensity for physical
      aggression and low anxiety best distinguished sons of male alcoholics (SOMAs)
      from non-SOMAs at both ages (6 and 12 years), even when SES was controlled. In
      addition, SOMAs were more oppositional and hyperactive than non-SOMAs at both
      ages. No significant effects were observed for family structure or age, or an
      interaction between these factors and paternal alcoholism in the multivariate
      analysis. CONCLUSIONS: The results suggest that problem behaviors in SOMAs begin
      early and persist over time, and that paternal alcoholism and family structure
      are not associated with changes in boys' behaviors between kindergarten and the
      end of elementary school in this population, at least in the sample used.

PMID- 9647422
TI  - Latent variable modeling of longitudinal and multilevel alcohol use data.
AB  - OBJECTIVE: This article demonstrates use of a latent variable model for
      longitudinal data which encompasses nested structures. Using Multilevel Latent
      Growth Modeling (LGM), levels of alcohol use and development of alcohol use over
      4 years were examined among individuals (adolescents and parents) nested within
      families. METHOD: An LGM model was tested for alcohol use with a sample of 435
      families (435 target adolescents, 203 sibling and 566 parents [168 fathers and
      398 mothers]). Adolescents (targets and siblings) comprised 312 boys and 326
      girls, with a mean (+/-SD) age at Time 1 (T1) of 13.69 +/- 1.95 years. It was
      hypothesized that there would be homogeneity in level and development of alcohol
      use among family members and heterogeneity in alcohol use and development across
      families. The effects of family status (single-parent, two-parent intact and
      stepparent families) and socioeconomic status (SES) on family levels of alcohol
      use were also examined. RESULTS: Results suggested that stepparent families, and
      less educated and more economically disadvantaged families, had higher family
      levels of alcohol use and developed in their use of alcohol at a faster rate.
      CONCLUSIONS: Findings suggest that the alcohol use of individuals in the same
      family is more alike than that of individuals from different families and that
      family alcohol use may be influenced by family-level variables such as family
      status or SES. Methods such as those presented, which incorporate family-level
      clustering, are likely to provide additional information regarding the etiology
      of alcohol use and risk factors for alcohol use within and across families.

PMID- 9647423
TI  - Alcohol outcome expectancies, attitudes toward drinking and the theory of planned
      behavior.
AB  - OBJECTIVE: The present study investigated whether alcohol outcome expectancies
      are empirically distinguishable from attitudes toward drinking. Specifically, the
      contribution of expectancies and attitudes to the Theory of Planned Behavior was
      assessed. METHOD: Undergraduates (N = 316; 170 male), of legal drinking age, who
      drank at least once a month participated. Intentions to drink "too much" and self
      report excessive consumption episodes served as criterion measures, and
      attitudes, subjective norm, perceived behavioral control and alcohol outcome
      expectancies were employed as predictor variables. Stepwise regression analyses
      were performed separately for men and women. RESULTS: The Theory of Planned
      Behavior appeared to be a valid framework for predicting excessive alcohol
      consumption among undergraduates. The predictive power of the model, however, was
      enhanced through the inclusion of gender-specific alcohol outcome expectancies.
      Specifically, in addition to attitudes and perceived behavioral control, women's
      expectancies for sociability enhanced the prediction of intentions to drink "too
      much." Expectancies for sexual functioning (male) and assertiveness (female)
      improved the prediction of excessive consumption, over and above intentions and
      perceived behavioral control. CONCLUSIONS: Alcohol outcome expectancies, unlike
      attitudes, are proximal predictors of excessive alcohol consumption among
      undergraduates.

PMID- 9647424
TI  - Differences in performance of screening instruments for problem drinking among
      blacks, whites and Hispanics in an emergency room population.
AB  - OBJECTIVE: The purpose of this study was to compare the performance of a number
      of standard screening instruments for alcohol dependence and harmful
      drinking/abuse by ethnicity (black, Hispanic and white) and by ethnicity and
      gender in an emergency room setting. METHOD: A probability sample of patients (N
      = 1,429) was breath analyzed and interviewed at the Santa Clara Valley Medical
      Center in San Jose, California. Sensitivity and specificity were analyzed among
      current drinkers (n = 857) for the CAGE, Brief MAST, AUDIT, TWEAK, RAPS and other
      items against combined ICD- 10 or DSM-IV criteria for alcohol dependence and
      separately for alcohol dependence or harmful drinking or abuse. RESULTS:
      Screening measures were not found to perform equally well by ethnicity or gender,
      with lower sensitivity found for women compared to men. Consistency in
      sensitivity of measures was found to vary considerably across ethnic and gender
      groups, with some measures (most notably the RAPS and the AUDIT) showing
      consistently high sensitivity across subgroups. None of the instruments performed
      nearly as well for identifying alcohol dependence or harmful drinking or abuse
      combined as for alcohol dependence alone. CONCLUSIONS: Analyses suggest that,
      while the RAPS may hold promise for identifying problem drinkers across ethnic
      and gender subgroups, it and other screening instruments currently in use require
      additional evaluation in a variety of settings to determine their usefulness for
      identifying those who could benefit from a brief intervention or referral for
      problem drinking.

PMID- 9647425
TI  - Psychometric evaluation of the Customary Drinking and Drug Use Record (CDDR): a
      measure of adolescent alcohol and drug involvement.
AB  - OBJECTIVE: The present study was undertaken to assess the psychometric
      characteristics of the Customary Drinking and Drug Use Record (CDDR), an
      interviewer-administered questionnaire. The CDDR provides current (past 3 months)
      and lifetime measures of four alcohol- and other drug-related domains: level of
      involvement, withdrawal characteristics, psychological/behavioral dependence
      symptoms, and negative consequences. The present report describes the evaluation
      of the psychometric properties of the instrument with youth between the ages of
      13 and 22 years who had markedly variable histories of involvement with alcohol
      and other psychoactive substances. METHOD: The sample assessed was composed of
      166 adolescents recruited from two inpatient substance abuse treatment programs
      and 115 adolescents recruited from the community. Of the 281 subjects, 150 were
      male. Follow-up interviews with each adolescent and a resource person were
      conducted 6, 12, 24 and 48 months after the initial assessment. RESULTS:
      Reliability of the CDDR was assessed by examination of internal consistency, test
      retest reliability and interrater reliability. Convergent, discriminant and
      construct validity were evaluated for each of the CDDR domains, and gender and
      ethnic differences on substance involvement were examined. The CDDR was found to
      be internally consistent and reliable over time and across interviewers for each
      major domain assessed. The findings supported the validity of the four domains of
      alcohol and other drug involvement assessed on the CDDR. CONCLUSIONS: The present
      results demonstrated convergent validity of the CDDR, ability to differentiate
      abusing from nonabusing youth and strong diagnostic specificity when compared to
      other standard instruments. The solid psychometric characteristics of the CDDR
      support its use for both research and clinical purposes.

PMID- 9647426
TI  - Screening college students for alcohol problems: psychometric assessment of the
      SASSI-2. Substance Abuse Subtle Screening Inventory.
AB  - OBJECTIVE: This study examined the psychometric properties of the Substance Abuse
      Subtle Screening Inventory (SASSI-2) with college students. METHOD: The first
      part of the study examined the test-retest reliability of the SASSI-2 at 2-week
      (n = 55) and 4-week (n = 47) intervals with students recruited from introductory
      psychology courses. The second part used a new sample of 164 college students to
      assess the internal consistency of the SASSI-2 subscales, the relationship of the
      SASSI-2 with other common alcohol screening instruments, and its reactivity to
      response biases. Participants completed the SASSI-2 under standard instructions,
      or instructions to minimize any alcohol problems they might have (fake good), or
      to exaggerate any alcohol problems they might have (fake bad). They then
      completed the CAGE, MAC and MAST under those measures' standard instructions.
      RESULTS: The 2-week and 4-week test-retest reliability of the SASSI-2 subscales
      was moderate to high, but the test-retest reliability for overall classification
      as "chemically dependent" or "non-chemically dependent" was moderate at 2 weeks
      and relatively poor at 4 weeks. Internal consistencies for the SASSI-2 subscales
      ranged from poor to strong (Cronbach alphas ranging from .11 to .93), and the
      SASSI-2 drinker classification status correlated moderately with drinker
      classifications based on the CAGE, MAC and MAST. There was no difference in the
      proportion of participants classified as "chemically dependent" on the SASSI-2
      when instructed to "fake good" and under standard instructions, but college
      students scored as "chemically dependent" more frequently when instructed to
      "fake bad." CONCLUSIONS: When the SASSI-2 is used with college students, its
      reliability and validity are comparable to other instruments that currently exist
      in the public domain. The vulnerability of the SASSI-2 to intentional faking
      warrants further investigation.

PMID- 9647427
TI  - Levels and patterns of alcohol consumption using timeline follow-back, daily
      diaries and real-time "electronic interviews".
AB  - OBJECTIVE: This study was designed to compare the Timeline Follow-Back (TLFB) to
      daily and real-time assessments of drinking. Our purpose was to evaluate overall
      correspondence and day-to-day agreement between these two methods among both
      problem and moderate drinkers. METHOD: In Study 1, problem drinkers (n = 20)
      reported their alcohol consumption daily during 28 days of brief treatment. In
      Study 2, moderate drinkers (n = 48), recruited from the community, used a palm
      top computer to record their drinking for 30 days. In both studies participants
      completed the TLFB covering the recording period. RESULTS: Participants in Study
      1 reported fewer drinking days, fewer drinks per drinking day and fewer total
      drinks per day on the TLFB, and those in Study 2 reported fewer drinks per
      drinking day, fewer ounces per drinking day, fewer total drinks per day and fewer
      total ounces per day. The magnitude of the difference, however, was modest. There
      was considerable between-person variation in day-to-day correspondence of TLFB
      and the daily and real-time reports. Neither person characteristics (gender,
      education and income) nor the distributional characteristics of drinking
      (including average consumption, variation) predicted concordance between TLFB and
      real-time reports. CONCLUSIONS: The Timeline Follow-Back method captured overall
      levels of drinking quite well compared to a 28-day daily diary and a 30-day
      electronic interview. Vast individual differences in day-to-day correspondence
      suggest that the TLFB may be less useful for detecting patterns of consumption.

PMID- 9647428
TI  - Time series analysis of alcohol consumption and suicide mortality in the United
      States, 1934-1987.
AB  - OBJECTIVE: The objective is to analyze time series data on per capita alcohol
      consumption and suicide mortality between 1934 and 1987. Specifically, the aim is
      to test the hypothesis that increases in per capita consumption are associated
      with increases in suicide mortality overall and in gender and age subgroups. This
      study also examines whether the effect of per capita consumption on subsequent
      rates of suicide is influenced by other aggregate factors, particularly
      unemployment rates, per capita income and divorce rates. METHOD: This analysis
      examines the temporal structure of suicide mortality, alcohol consumption and
      covariate time series data in the United States, 1934-1987, using the Box-Jenkins
      method. RESULTS: Bivariate associations between alcohol consumption and suicide
      rates were not significant. However, when unemployment was included in the model,
      increases in per capita alcohol consumption were significantly related to
      increases in suicide overall, for men and women, and for the young (under age 40)
      and middle-aged (40 to 59 years), but not for those over age 60. CONCLUSIONS: The
      use in modeling of other known covariates of suicide rates, particularly
      unemployment, affects the magnitude of the relationship between alcohol
      consumption and suicide. Consistent with other studies, unemployment was
      significantly related to suicide and was shown to confound the relationship
      between alcohol and suicide. The effects of changes in alcohol consumption on
      changes in suicide rates differ by gender and age group, which demonstrates that
      focusing on the total population alone can mask divergent effects that can cancel
      each other out when subgroups are combined.

PMID- 9647429
TI  - Costs and benefits of a community sobriety checkpoint program.
AB  - OBJECTIVE: Alcohol-involved crashes cost society more than $100 billion a year.
      Sobriety checkpoints are effective in apprehending drunk drivers. This article
      compares the costs and the estimated monetary benefits from a hypothetical
      community sobriety checkpoint program. METHOD: The analysis is constructed around
      a hypothetical community with 100,000 licensed drivers. A literature review
      suggests that a generously funded intensive checkpoint program (156 checkpoints
      per year) can be expected to reduce alcohol-attributable crashes by about 15%.
      The benefits (cost savings) of the checkpoint program are calculated using 1993
      alcohol-involved crash incidence from the National Highway Traffic Safety
      Administration. Costs per alcohol-involved crash and the percentage of alcohol
      involved crashes attributable to alcohol are updated from published studies.
      RESULTS: Estimated annual savings to the hypothetical community total $7.9
      million. This includes $3.1 million for averted fatalities, $4.5 million for
      averted non-fatal injuries, and $0.3 million for averted property damage. Every
      $1 spent on a sobriety checkpoint program can be expected to save the community
      more than $6, including $1.30 of insurer costs. CONCLUSIONS: An intensive
      sobriety checkpoint program can save a community more in automobile crash costs
      than the program costs.

PMID- 9647430
TI  - The origins and evolution of the disease concept of treatment.
AB  - OBJECTIVE: The disease concept of treatment (DCT) has been the dominant treatment
      model for alcoholism in the United States for the last 30 years. This article
      sheds light on this treatment model by tracing its historical origins and its
      evolution in institutions. METHOD: Accounts from the published literature on
      Alcoholics Anonymous (AA) and early alcoholism treatment programs were culled for
      insights regarding the development of DCT. Early examples of AA facilities, state
      mental hospital alcoholism units, detoxification units, and outpatient alcoholism
      clinics are described as they evolved. The important role of AA in this process
      is detailed. Accounts are given of the interaction between professionals and
      alcoholism counselors during the period in which DCT was developed in these
      institutions. RESULTS: It was found that all of the current types of alcoholism
      treatment programs had their origins in early, informal AA facilities except for
      outpatient alcoholism clinics. DCT evolved concurrently in AA facilities, state
      mental hospitals and detoxification units. CONCLUSIONS: The historical accounts
      summarized here suggest that DCT was primarily a structured and didactic
      presentation of AA principles that incorporated some additional treatment
      elements, notably, the confrontation group. Thus, it can be argued that most
      alcoholism treatment today (i.e., DCT) derives from the original AA model. It is
      suggested that studies be undertaken to distinguish the degree to which AA
      recovery principles are different from DCT methods by researching the clinical
      beliefs and practices of alcoholism counselors and comparing them with those of
      AA members.

PMID- 9647431
TI  - Overdiagnosis of major psychiatric disorders in individuals with substance use
      disorders and personality disorders: the downside of the Woodruff principle.

PMID- 9647432
TI  - One-year chromaffin cell allograft survival in cancer patients with chronic pain:
      morphological and functional evidence.
AB  - The control of chronic pain through transplantation of chromaffin cells has been
      reported over the past few years. Analgesic effects are principally due to the
      production of opioid peptides and catecholamines by chromaffin cells. Clinical
      trials have been reported with allografts consisting of whole-tissue fragments
      implanted into the subarachnoid space of the lumbar spinal cord (14,19,36). In
      the present study, allogeneic grafts were successfully used to control chronic
      pain in two patients over a period of 1 yr based on patient reported pain scores,
      morphine intake, and CSF levels of Met-enkephalin. Macroscopic examination at
      autopsy located the transplanted tissue fragments in the form of multilobulated
      nodules at the level of the spinal axis and cauda equina. Immunocytochemical
      microscopy showed neuroendocrine cells are positive for chromagranin A (CGA), and
      enzymes tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DbetaH). The
      results suggest that there is a relationship between analgesic effect, Met
      enkephalin levels in CSF, and the presence of chromaffin cells surviving in
      spinal subarachnoid space.

PMID- 9647433
TI  - Cardiomyocyte transplantation in a porcine myocardial infarction model.
AB  - Transplantation of cardiomyocytes into the heart is a potential treatment for
      replacing damaged cardiac muscle. To investigate the feasibility and efficiency
      of this technique, either a cardiac-derived cell line (HL-1 cells), or normal
      fetal or neonatal pig cardiomyocytes were grafted into a porcine model of
      myocardial infarction. The myocardial infarction was created by the placement of
      an embolization coil in the distal portion of the left anterior descending artery
      in Yorkshire pigs (n = 9). Four to 5 wk after creation of an infarct, the three
      preparations of cardiomyocytes were grafted, at 1 x 10(6) cells/20 microL into
      normal and into the middle of the infarcted myocardium. The hearts were harvested
      and processed for histologic examinations 4 to 5 wk after the cell grafts.
      Histologic evaluation of the graft sites demonstrated that HL-1 cells and fetal
      pig cardiomyocytes formed stable grafts within the normal myocardium without any
      detrimental effect including arrhythmia. In addition, a marked increase in
      angiogenesis was observed both within the grafts and adjacent host myocardium.
      Electron microscopy studies demonstrated that fetal pig cardiomyocytes and the
      host myocardial cells were coupled with adherens-type junctions and gap
      junctions. Histologic examination of graft sites from infarct tissue failed to
      show the presence of grafted HL-1 cells, fetal, or neonatal pig cardiomyocytes.
      Cardiomyocyte transplantation may provide the potential means for cell-mediated
      gene therapy for introduction of therapeutic molecules into the heart.

PMID- 9647434
TI  - Intrasplenic liver parenchymal cells in conjunction with low-dose rapamycin and
      cyclosporine induce a unique and specific prolongation of rat cardiac and small
      bowel allograft survival.
AB  - These experiments investigated the immunosuppressive properties of liver tissue.
      Brown Norway (BN; RT1n) rat heart allografts survived in untreated control Wistar
      Furth (WFu; RTl(u)) rat recipients for 6.2 +/- 1.5 days, while allografts in
      animals that received rapamycin (RAPA) 0.0075 mg/kg/day and cyclosporine (CsA)
      0.375 mg/kg/day delivered for 14 days by continuous intravenous infusion (civi)
      using osmotic pumps in conjunction with intrasplenic (i.s.) saline survived to
      18.4 +/- 1.3 days. i.s. addition of 3 M-KCl extracted BN hepatic antigen or
      unpurified BN hepatocytes (liver parenchymal cells-5 x 10(7)/kg), which exhibited
      a 4.8% class II antigen expression, and which alone failed to prolong allograft
      survival (MST = 6.0 +/- 1.4 days), increased heart allograft survival to 25.3 +/-
      2.3 and 27.2 +/- 1.9 days, respectively (p < 0.01). Hepatocyte purification using
      Dynabeads and Percoll reduced class II expression to 0.9% and increased allograft
      survival to 32.8 +/- 1.6 days (p < 0.01). In contrast, the effect of 5 x 10(8)/kg
      BN erythrocytes, exhibiting only 0.1% class II expression, was much less (23.8 +/
      1.9 days). Administration i.s. of BN splenocytes or nonparenchymal liver cells,
      demonstrated by flow cytometry to exhibit a 47.3 or 55.1% expression of class II
      antigen, respectively, failed to induce any significant increase in allograft
      survival (18.4 +/- 4.6 and 19.4 +/- 0.5 days, respectively). Survival of BN rat
      small bowel allografts was increased in Lewis (LEW; RTl1) rat recipients treated
      with RAPA, CsA, and unfractionated BN hepatocytes from 10.2 +/- 1.9 to 21.2 +/-
      1.5 days. Pretreatment with i.s. BN hepatocytes, 14 days prior to harvesting,
      reduced WFu lymphocyte responses to allogeneic stimulation with BN or ACI spleen
      cells by 75 and 70%, respectively. Addition of 1 x 10(5) unpurified donor
      specific BN or third-party Buffalo (BUF; RTl(b)) hepatocytes, but not
      supernatant, to the responder wells of MLCs resulted in a 61 and 40% suppression,
      respectively, of the WFu lymphocyte response induced by BN allogeneic
      stimulation. These findings suggest that while class I MHC expression has a
      significant role to play in exerting the immunosuppressive effects of
      hepatocytes, other influences more specific to liver may also prevail.

PMID- 9647435
TI  - Response of cultured fetal and adult rat hepatocytes to growth factors and
      cyclosporine.
AB  - Hepatocyte transplantation is a promising alternative to orthotopic liver
      transplantation in experimental animal models with genetic disorders of liver
      metabolism and liver failure. Fetal hepatocytes have several characteristics that
      make them potentially suitable as donor cells. In contrast to adult hepatocytes,
      fetal hepatocytes are thought to be highly proliferative, which may facilitate
      engraftment, expansion of transplanted cell population, and gene transfer
      requiring active DNA synthesis. The present study was undertaken to evaluate the
      proliferative capacity of fetal and adult rat hepatocytes under standardized
      culture conditions. Fetal (20 days of gestation) and adult hepatocytes were
      cultured in serum-free media at low densities and treated with growth factors.
      Proliferation was assessed by [3H]-thymidine incorporation and cell cycle
      analysis by flow cytometry. In nonstimulated cells, DNA synthesis at 4 h was
      about x100 higher and after 10 days in culture x20 higher in fetal compared to
      adult hepatocytes. When epidermal growth factor (EGF) was added, maximal DNA
      synthesis in fetal hepatocytes was seen at 48 h, whereas in adult hepatocytes at
      72 h. For adult hepatocytes, the average increase compared to untreated cells was
      x13.8 with EGF, x18.5 with transforming growth factor alpha (TGF-alpha), and x7.6
      with hepatocyte growth factor (HGF). For fetal hepatocytes, the increase was
      twofold with either EGF, TGF-alpha or HGF. EGF-, TGF-alpha- and HGF-dependent DNA
      synthesis was inhibited by transforming growth factor beta-1 (TGF-beta1) in both
      fetal and adult hepatocyte cultures; this antiproliferative effect was
      significantly stronger in adult hepatocyte cultures. With cyclosporine, EGF-, TGF
      alpha- and HGF-dependent DNA synthesis in fetal hepatocyte cultures decreased by
      36-46%, whereas in adult hepatocytes by 19-27 %. These results show that in
      contrast to adult hepatocytes, fetal hepatocytes have high spontaneous
      proliferative activity independently of growth factors and are relatively
      resistant to the inhibitory effect of TGF-beta1. It was also found that
      cyclosporine suppresses proliferation of cultured fetal hepatocytes.

PMID- 9647436
TI  - In vivo identification, survival, and functional efficacy of transplanted
      hepatocytes in acute liver failure mice model by FISH using Y-chromosome probe.
AB  - Hepatocyte transplantation has excited much interest in lending temporary
      metabolic support to a failing liver following acute liver injury. The exact site
      from which they act and the clinical, biochemical, and histological changes in
      the recipient body following hepatocyte transplantation is yet to be worked out.
      The present study is an attempt to delineate location and function of
      transplanted hepatocytes and also the overall survival of these cells with a
      fluorescent in situ hybridization (FISH) technique using a Y-chromosome-specific
      probe in a carbon tetrachloride (CCl4)-induced mice model of fulminant hepatic
      failure. Fifty-five syngenic adult Swiss female mice of approximately the same
      age and body weight were divided into three groups. Group-1 (n = 15), which
      received mineral oil, served as a negative control. Group-II (n = 15) received
      CCl4 (3 mL/kg) 40% vol/vol in mineral oil, by gavage served as positive control
      for hepatic failure. Group-III (n = 25) received intrasplenic transplantation of
      syngenic single cell suspension of hepatocytes in Hanks medium, after 30 h of
      CCl4 administration. Male Swiss adult mice (n = 15) served as donors of
      hepatocytes. The overall survival of animals in groups I to III was 100, 0, and
      70%, respectively, by 2 wk of the study period. Transplanted hepatocytes were
      identified by Periodic Acid Schiff (PAS) staining and confirmed with a FISH
      technique using the Y-chromosome probe. The majority of exogenously transplanted
      hepatocytes were found in the liver and spleen sections even after 1 wk of
      hepatocyte transplantation. Transplanted cells were mostly found to be
      translocated into the sinusoids of the liver. Transplanted hepatocytes were found
      to be beneficial as a temporary liver support in a failing liver, significantly
      improving the survival of the animals. In the present study, the FISH technique
      was used to unequivocally distinguish the transplanted cells from the host, and
      thus describes a model for studying the distribution and survival of the
      transplanted cells.

PMID- 9647437
TI  - Human serum albumin microspheres approximate initial organ-specific
      biodistributions of transplanted hepatocytes and are effective cell surrogates
      for safety studies.
AB  - Liver repopulation with transplanted hepatocytes will generate novel cell-based
      therapies, although translocation of transplanted cells into lungs through
      portasystemic shunts has the potential for embolic complications. To facilitate
      safety analysis of hepatocyte transplantation, we wished to obtain effective cell
      surrogates and analyzed biodistributions of similarly sized 99mTc-labeled human
      serum albumin microspheres and rat hepatocytes. Image analysis with dual 99mTc
      and 111In labels indicated that cells and microspheres were similarly distributed
      in the liver when injected into normal rats via the spleen. Also, their
      distributions were similar when injected via a femoral vein or the superior
      mesenteric vein with cells and microspheres localizing in lungs or liver,
      respectively. Upon intraportal injection in rats with portal hypertension,
      microspheres localized in both liver and lungs, consistent with portasystemic
      shunting. These data demonstrate that human serum albumin microspheres are
      effective cell surrogates for approximating the safety of hepatocyte
      transplantation and should be clinically useful.

PMID- 9647438
TI  - Islet allograft rejection in rats: a time course study characterizing adhesion
      molecule expression, MHC expression, and infiltrate immunophenotypes.
AB  - Wistar Furth (RT1u) islets transplanted under the renal capsules of
      streptozotocin-diabetic Lewis (RT1l) rats reject after 5-6 days of normoglycemia.
      Hand-picked WF islets (1500-2000) were transplanted under the kidney capsules of
      diabetic Lew or WF rats. Rats bearing iso- or allografts were killed on
      posttransplant days 2, 4, and 6. Serial frozen sections of grafts and controls
      were stained by immunoperoxidase for rat MAC-1, class II MHC, CD2, CD4, CD8, B
      cells, VLA-4, LFA-1, L-selectin, ICAM-1, and VCAM-1. Infiltrating cells,
      parenchymal cells, and endothelial cells in five distinct compartments (i.e.,
      peritoneal reflection, subcapsular perivascular space, islet grafts, graft-kidney
      interface, and kidney) were evaluated for expression of the various markers at
      each interval. Significant infiltrates arrived in three distinct waves in both
      iso- and allografts. First, macrophages blanketed the peritoneal capsular
      reflection and infiltrated by day 2. Second, the first wave of lymphocytes
      arrived in the edematous subcapsular soft tissue via capsular vessels by day 2
      (allo > iso). Third, the second wave of lymphocytes arrived from the renal
      parenchyma to form a dense band at the graft-kidney interface and around grafts
      by days 4 and 6 (allo >>> iso); CD4+ cells vastly outnumbered CD8+ cells, with
      CD4+ cells being mobilized first and from interstitial vessels throughout the
      entire kidney. CD8+ cells emigrated only from renal interstitial vessels adjacent
      to the graft. Large numbers of L-selectin+, VLA-4+, and LFA-1+ cells were seen in
      the infiltrates with the most intensely staining cells being intravascular. B
      cells composed a very small proportion of infiltrating cells in both allo- and
      isografts. Endothelial staining for ICAM-1 and VCAM-1 was prominent throughout.
      Both class II MHC and ICAM-1 expression were induced on renal tubular epithelial
      cells, but neither was found on islet parenchymal cells. In conclusion, this
      study shows that islet allograft rejection is more complex than previously
      realized.

PMID- 9647439
TI  - Tilapia--a source of hypoxia-resistant islet cells for encapsulation.
AB  - Encapsulation of pancreatic islets prevents graft revascularization after
      transplantation, resulting in graft hypoxia and attrition. Hypoxia-resistant
      islets would be ideal for encapsulation. Tilapia, a tropical teleost fish, have
      large, anatomically discrete islets that can be easily harvested without
      expensive, fickle islet isolation procedures and that provide mammalian-like
      glucose tolerance profiles when transplanted into diabetic recipients. Because
      tilapia can live in stagnant water, we speculated that tilapia islets might
      tolerate lower oxygen tensions than mammalian islets. Tilapia and rat islets (n =
      30) were placed in paired 60-mm Petri dishes containing 10 mL of deoxygenated
      CMRL-1066 media and cultured together in sealed chambers gassed with 95% N2/5%
      CO2. Islet viability was determined by fluorscein diacetate/ethidium bromide
      staining at intervals varying from 2.5 h to 7 days; blood gas measurements were
      obtained on media samples at the end of selected incubation intervals. Rat islets
      underwent near-total necrosis and fragmentation in <24 h; occasional viable
      single cells could be identified until about 72 h. On the other hand, the fish
      islets showed no loss of viability until about 72 h when some showed mild central
      necrosis. Even at 7 days, all fish islets appeared roughly 50% viable. Fish
      islets cultured under hypoxic conditions for 72 h (media, pO2 = 27.8 mmHg) and
      then transplanted into streptozotocin-diabetic athymic nude mice were viable
      (6/6) but showed some diminished function (3/6) over a 25-day follow-up period.
      Our results suggest that tilapia islets will survive and function at lower oxygen
      tensions than mammalian islets.

PMID- 9647440
TI  - Single-cell suspensions of cultured human keratinocytes in fibrin-glue
      reconstitute the epidermis.
AB  - To overcome common disadvantages of standard cultured epidermal sheet grafts
      (CEG) we have developed a new technique of transplanting cultured human
      keratinocytes suspended as single cells in a fibrin-glue matrix (Keratinocyte
      fibrin-glue suspension-KFGS). In an athymic mouse model with reproducible
      standardized full thickness wounds this new technique was compared directly to
      CEG. Reepithelialization was similar in both groups, but reconstitution of the
      dermo-epidermal junction zone, as shown by electron microscopy and
      immunohistochemistry was significantly enhanced by the fibrin-glue suspension
      technique. The new KFGS technique is earlier available than sheet grafts, is able
      to transfer actively proliferative single keratinocytes, and simplifies the
      application.

PMID- 9647441
TI  - Perfusion enhances functions of bone marrow stromal cells in three-dimensional
      culture.
AB  - Perfusion of medium through three-dimensional (3D) collagen sponges enhanced
      viability and function of cocultivated marrow stromal and hematopoietic cell
      lines. Cells of the murine bone marrow stromal cell line GPIa were cultured in
      novel 3D collagen sponges, made from pepsin-digested bovine skin. Static cultures
      of sponges were maintained in dishes with media changes every other day. Perfused
      sponges were contained in a glass column with medium flow set at 1.3 mL/min. In
      some sponges, the 32D cl3 c-fms(m) (CRX-1) hematopoietic progenitor cell line was
      added 7 days after GPIa cells. At 7 and 16 days, light microscopic evaluation
      showed poor viability of cells in static sponge cultures. In perfused sponge
      cultures, there was greater cellularity throughout the sponge and abundant
      accumulation of metachromatic extracellular matrix surrounding GPIa cells.
      Chondroitin 6-sulfate and heparan sulfate were identified as components of the
      matrix by immunohistochemical methods. DNA synthesis was evaluated by 15-h
      exposure of cultures to bromodeoxyuridine (BrdU), with subsequent
      immunohistochemical localization with monoclonal anti-BrdU antibody. Cells
      positive for BrdU were identified at the outer surfaces of both static and
      perfused sponges; however, positive cells were also seen throughout the internal
      areas of the sponges that were perfused. These results suggest that better
      nutrient exchange occurred in perfused sponges. In static cocultures of GPIa and
      CRX-1 cells, there was no detectable viability of the IL-3-dependent CRX-1 cells;
      however, under perfused conditions, CRX-1 cells flourished within the sponges as
      documented by BrdU incorporation. Thus, medium perfusion enhanced GPIa stromal
      cell line viability and function in 3D collagen sponge cultures, as demonstrated
      by BrdU incorporation, matrix production, and support of CRX-1 cells. This novel
      culture system may be useful for examining the interactions of bone marrow
      stromal cells with extracellular matrix molecules, soluble and matrix-bound
      factors, and with other cell types.

PMID- 9647442
TI  - Measurement of myocardial infarct size by electron beam computed tomography: a
      comparison with 99mTc sestamibi.
AB  - RATIONALE AND OBJECTIVES: The authors sought to determine, using a variety of
      regional left ventricular ejection fraction (EF) and wall thickening (WTh)
      criteria, the applicability to measure left ventricular (LV) infarct size using
      electron-beam CT (EBCT) in patients as compared with technetium 99m (99mTc)
      sestamibi scanning as reference standard. METHODS: Twelve patients (age 57 +/- 11
      years) underwent 99mTc sestamibi scanning and EBCT at hospital discharge after an
      acute index anterior myocardial infarction. Left ventricular infarct size was
      defined using standard 99mTc sestamibi scanning. Regional EF and WTh were
      analyzed on each EBCT scan with use of a floating epicardial centroid method. In
      five contiguous LV tomograms, the amount of infarcted myocardium was estimated
      using the following EF and WTh criteria: EF < or = 35%, 30%, 25%, 20%, and WTh <
      or = 2 mm, 1 mm, and 0 mm. RESULTS: Infarct size measured with 99mTc sestamibi
      was 33.3% (+/- 18.3%) (mean +/- SD, range 6%-54%) of the LV. Using an EF < or =
      35% or absolute WTh < or = 2 mm as criteria for infarcted myocardium, EBCT
      yielded 28% (+/- 17%) and 27% (+/- 16%), respectively (P = NS, paired Student's t
      test, versus 99mTc sestamibi). Although, with use of the other criteria, EBCT
      tended to underestimate infarct size compared with 99mTc sestamibi, a close
      correlation across the entire range of infarct size determinations (range, 0.72
      0.82) regardless of the underlying criteria suggested an internal consistency of
      the data. CONCLUSIONS: Quantitative analysis of regional myocardial function by
      EBCT allows an estimate of anterior infarct size when compared with 99mTc
      sestamibi. This suggests that in addition to previously established applications
      after acute myocardial infarction such as examination of cardiac volumes and
      mass, EBCT also may provide for infarct size determination.

PMID- 9647443
TI  - A new model of endovascularly induced renal artery stenosis in
      normocholesterolemic versus hypercholesterolemic rabbits.
AB  - RATIONALE AND OBJECTIVES: The authors determine the feasibility of creating renal
      artery stenosis by overdilatation and deendothelialization and compare the model
      in normocholesterolemic versus hypercholesterolemic rabbits. METHODS: Thirty male
      New Zealand White rabbits were randomized into two groups: group A (n = 15) was
      fed a normal diet and group B (n = 15) was fed a cholesterol-rich diet 4 weeks
      before stenosis induction. An aortogram was performed, then the right renal
      artery was overdilated with an angioplasty balloon-catheter, and
      deendothelialized. After 6 weeks, groups A and B were compared by angiographic
      and pathologic study. RESULTS: Comparison of group A versus group B showed that
      12 arteries (80%) versus 6 (40%) were angiographically stenotic (P < 0.05); 14
      (93%) versus 12 (80%) contained neointima (NS), 12 (80%) versus 3 (20%) showed
      medial disorganization (P < 0.01), and 9 (60%) versus 2 (13%) presented
      adventitial fibrosis (P < 0.01). CONCLUSIONS: A new model of endovascularly
      induced renal artery stenosis has been developed in rabbits. Medial proliferation
      and adventitial fibrosis are more frequent in normocholesterolemic rabbits.

PMID- 9647444
TI  - Dynamic phosphorus-31 magnetic resonance spectroscopy in arterial occlusive
      disease: effects of vascular therapy on spectroscopic results.
AB  - RATIONALE AND OBJECTIVES: The aim of the authors' prospective study was to
      explore therapy-induced changes of muscular metabolism in arterial occlusive
      disease (AOD). MATERIALS: Before and after vascular therapy, respectively, 31
      patients with AOD were examined by dynamic phosphorus-31 (31P) magnetic resonance
      spectroscopy (MRS) at 1.5 T; in the magnet, the quadriceps muscle was stressed by
      an isometric and an isotonic form of exercise until exhaustion, respectively.
      Twenty-three patients were treated by standardized percutaneous transluminal
      angioplasty; eight patients underwent a vascular operation. RESULTS: Vascular
      therapy induced a marked improvement of clinical and angiographic results. At the
      same work load, exercise-induced metabolic changes of the quadriceps muscle were
      significantly less pronounced after the vascular therapy: maxima of the ratio
      inorganic phosphate (Pi)/phosphocreatine (PCr) (isometric exercise: 0.34 [after
      therapy] versus 0.44 [before therapy]; isotonic exercise: 0.36 [after therapy]
      versus 0.51 [before therapy]) as well as minima of pH (isometric exercise: 7.00
      [after therapy] versus 6.93 [before therapy]; isotonic exercise: 7.00 [after
      therapy] versus 6.93 [before therapy]). In relation to maximal values of Pi/PCr,
      the extent of acidosis was smaller after vascular therapy, resulting in a flatter
      slope of the regression line between these parameters (b = -0.24 +/- 0.10 versus
      b = -0.31 +/- 0.09). After both of the exercises, time of half recovery of Pi/PCr
      was significantly shorter after vascular therapy (isometric exercise: 43 seconds
      [after therapy] versus 83 seconds [before therapy]; isotonic exercise: 42 seconds
      [after therapy] versus 57 seconds [before therapy]). CONCLUSIONS: After effective
      vascular therapy, minor exercise-induced metabolic changes (increased
      "work/energy cost-index"), a decreased contribution of anaerobic glycolysis to
      total adenosine triphosphate production as well as a markedly increased recovery
      rate of Pi/PCr are unequivocal spectroscopic proofs of an improved oxidative
      metabolism of muscle cells because of increased tissue perfusion.

PMID- 9647445
TI  - Echoplanar BOLD fMRI of brain activation induced by concurrent transcranial
      magnetic stimulation.
AB  - RATIONALE AND OBJECTIVES: The authors demonstrate the feasibility of combining
      transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging
      (fMRI) inside an MR scanner to noninvasively stimulate and image regional brain
      activity. METHODS: Echoplanar blood oxygen level dependent (BOLD)-based fMRI
      studies of TMS response were performed on three human volunteers inside a
      standard 1.5 T MR scanner using independent computer control to interleave
      echoplanar image acquisition and stimulation of right thumb primary motor cortex
      with a nonferromagnetic TMS coil. RESULTS: Significant (P< 0.001) response was
      observed in motor cortex under the TMS coil during stimulation compared to rest,
      as well in auditory cortex, the latter presumably due to the loud "snap" when the
      coil was pulsed. CONCLUSIONS: Concurrent TMS stimulation and echoplanar BOLD fMRI
      imaging is possible. This method has potential for tracing neural circuits with
      brain imaging, as well as investigating the effects of TMS.

PMID- 9647446
TI  - Diagnostic evaluation of sonographically visualized breast lesions by using a new
      clinical amplitude/velocity reference imaging technique (CARI sonography).
AB  - RATIONALE AND OBJECTIVES: The goal of this study was to evaluate and
      differentiate breast lesions in patients by sonographic measurements performed
      using CARI sonography. METHODS: Thirty-one patients with 33 histologically proven
      breast lesions were examined by mammography, conventional ultrasound sonography,
      and CARI sonography. Investigation with mammography-like positioning was
      performed in case of CARI sonography. The ratios of the lesion diameters were
      calculated in a craniocaudal and a mediolateral plane. The results were compared
      with the results obtained with conventional modalities. RESULTS: Breast lesions
      were detected with the best sensitivity (100%) and a high specificity (86%) using
      B-mode ultrasound sonography. Mammography resulted in a sensitivity of 92% and a
      specificity of 91%, whereas the CARI sonography yielded 100% sensitivity and 67%
      specificity. CONCLUSIONS: The differentiation of lesions by measurements
      performed with CARI sonography resulted in a high sensitivity. The specificity,
      however, was inferior compared with the other imaging modalities. This may limit
      the routine application of the technique for clinical diagnoses of breast
      lesions. However, due to the small number of patients investigated in this pilot
      study, the full potential should be evaluated in a larger collective of patients.

PMID- 9647447
TI  - Abdominal image segmentation using three-dimensional deformable models.
AB  - RATIONALE AND OBJECTIVES: The authors develop a three-dimensional (3-D)
      deformable surface model-based segmentation scheme for abdominal computed
      tomography (CT) image segmentation. METHODS: A parameterized 3-D surface model
      was developed to represent the human abdominal organs. An energy function defined
      on the direction of the image gradient and the surface normal of the deformable
      model was introduced to measure the match between the model and image data. A
      conjugate gradient algorithm was adapted to the minimization of the energy
      function. RESULTS: Test results for synthetic images showed that the
      incorporation of surface directional information improved the results over those
      using only the magnitude of the image gradient. The algorithm was tested on 21 CT
      datasets. Of the 21 cases tested, 11 were evaluated visually by a radiologist and
      the results were judged to be without noticeable error. The other 10 were
      evaluated over a distance function. The average distance was less than 1 voxel.
      CONCLUSIONS: The deformable model-based segmentation scheme produces robust and
      acceptable outputs on abdominal CT images.

PMID- 9647448
TI  - Influence of contrast media on the response of rat renal arteries to endothelin
      and nitric oxide: influence of contrast media.
AB  - RATIONALE AND OBJECTIVES: Contrast media (CM) such as diatrizoate meglumine (DTZ)
      or iohexol can cause renal vasoconstriction in vivo, and this may initiate CM
      induced nephropathy. Endothelin-1 (ET-1), a vasoconstrictor, and nitric oxide, a
      vasodilator, are key modulators of renal circulation. We tested the hypothesis
      that CM enhances arterial responses to ET-1, or diminishes responses to nitric
      oxide. METHODS: A video dimension analyzer continuously recorded changes in
      diameter of isolated, pressurized rat interlobar renal arteries (200-400 microm
      diameter) superfused with combinations of CM, ET-1, nitric oxide, and other
      vasoactive agents. RESULTS: Superfusion of arteries with 3.3% DTZ, but not with
      3.3% iohexol, enhanced their sensitivity to ET-1 by approximately twofold, as
      assessed by shifts in concentration-response curves. Both DTZ and iohexol
      decreased the sensitivity of arteries to nitric oxide by approximately threefold.
      Neither DTZ nor iohexol affected arterial sensitivity to other vasoconstrictors
      (phenylephrine, potassium) or vasodilators (forskolin, diltiazem). CONCLUSIONS:
      Diatrizoate meglumine and iohexol may induce or augment renal vasoconstriction in
      part by causing selective alterations in arterial sensitivity to ET-1 and to
      nitric oxide.

PMID- 9647449
TI  - Are superabsorbers useful for endovascular embolization of saccular aneurysms? An
      in vitro study.
AB  - RATIONALE AND OBJECTIVES: The authors conducted in vitro evaluation of
      superabsorber for endovascular embolization of saccular aneurysms. METHODS: The
      swelling properties of the superabsorber Sanwet IM-7000 were investigated in
      various solvents. The material used was granulate (group A: particle size
      approximately 459 microm; group B: particle size approximately 20 microm) as well
      as cubes with an edge length of 1 mm prepared from a block. With ascending
      concentrations of Sanwet IM-7000 held in suspensions made of Lipiodol and 96%
      ethanol, the injectability was determined using microcatheters (2.1 F/3 F). The
      behavior of Sanwet IM-7000 as occlusion material for aneurysms was examined in a
      sacciform glass-model aneurysm. RESULTS: The granule showed no significant
      increase in size in Lipiodol and in 96% ethanol, so that they were chosen for
      catheter measurement. In Lipiodol suspension the maximum fraction of the
      granulate suitable for injection through a 3 F catheter was 3.2%. In 96% ethanol
      suspension the maximum fraction of granulate suitable for injection through a 3 F
      catheter was 0.8%. Suspended in Lipiodol Sanwet IM-7000 showed a moderate
      swelling in the aneurysm model, whereas the use of 96% ethanol resulted in a
      pronounced swelling of the granulate (100 vol%) after the 96% ethanol was washed
      off. Irrespective of the granulate size used, a rinse-off process of the
      granulate occurred in the model aneurysm at a flow rate above 200 mL x min(-1).
      Cubes prepared from a block of the base polymerisate of Sanwet IM-7000 showed a
      delayed increase in size. The final size in 0.9% NaCl solution was reached in the
      cubes after 220 min, in the granulate already after 20 mins. The cubes displayed
      a high form stability. CONCLUSIONS: Due to the substance-related absence of
      intercorporeal cross-linking and the unpredictable increase in size, embolization
      of aneurysms using Sanwet IM-7000 granulate is inadvisable at present. In spite
      of a longer swelling time and because of its form consistency, the use of
      prepared cubes could provide a reasonable alternative.

PMID- 9647450
TI  - Review of the effectiveness of capsaicin for painful cutaneous disorders and
      neural dysfunction.
AB  - BACKGROUND: Topical capsaicin is known to be a safe and effective pain management
      adjunct for rheumatoid arthritis, osteoarthritis, neuralgias, and diabetic
      neuropathy. However, studies and case reports in the literature have indicated
      that other conditions may also benefit from capsaicin: painful or itching
      cutaneous disorders from operations, injuries, or tumors; neural dysfunction; or
      inflammation of the airways and urinary tract. METHODS: To determine the
      effectiveness of capsaicin for painful cutaneous disorders and neural
      dysfunction, the authors analyzed data from 33 reports (MEDLINE search of 1966
      96) on the efficacy of capsaicin. Outcome measures consisted of the response rate
      and degree of pain relief. Results from placebo-controlled trials were pooled
      when possible; effect of treatment was estimated by the method of DerSimonian and
      Laird. RESULTS: Pain relief for postmastectomy syndrome and cluster headache was
      greater with capsaicin than with placebo; also, psoriasis and pruritus responded
      better to capsaicin. Uncontrolled studies and case reports have indicated that
      pain or dysfunction was less at the end of capsaicin therapy for neck pain, loin
      pain/hematuria syndrome, oral mucositis, rhinopathy, reflex sympathetic dystrophy
      syndrome, detrusor hyperreflexia, and cutaneous pain due to tumor of the skin.
      CONCLUSIONS: Capsaicin is effective for psoriasis, pruritus, and cluster
      headache; it is often helpful for the itching and pain of postmastectomy pain
      syndrome, oral mucositis, cutaneous allergy, loin pain/hematuria syndrome, neck
      pain, amputation stump pain, and skin tumor; and it may be beneficial for neural
      dysfunction (detrusor hyperreflexia, reflex sympathetic dystrophy, and
      rhinopathy). A universal problem for many of the studies analyzed was the absence
      of a "burning placebo" such as camphor.

PMID- 9647451
TI  - Social context of pain in children with Juvenile Primary Fibromyalgia Syndrome:
      parental pain history and family environment.
AB  - OBJECTIVE: The purpose of this study was to describe parental pain history and
      the family environment as it relates to the functional status of children with
      Juvenile Primary Fibromyalgia Syndrome (JPFS). DESIGN AND OUTCOME MEASURES:
      Twenty-nine parents of children with JPFS completed a pain history questionnaire,
      Von Korff Chronic Pain Grading system, and the Family Environment Scale (FES).
      Twenty-one adolescents with JPFS completed the FES, the Visual Analogue Scale for
      Pain, the modified Fibromyalgia Impact Questionnaire for Children, the Arthritis
      Impact Measurement Scales, and the Symptom Checklist-90-Revised. Correlational
      analyses were performed. RESULTS: Parents of children with JPFS reported multiple
      chronic pain conditions, including but not limited to fibromyalgia. Parental pain
      history and the family environment correlated with the health status of
      adolescents with JPFS. Children with JPFS perceived the family environment as
      significantly more cohesive than did their parents. Greater incongruence between
      parent and child responses on the FES positively correlated with greater
      impairment. CONCLUSIONS: These results suggest that family environment and
      parental pain history ay be related to how children cope with JPFS. Behavioral
      interventions targeting the family may improve the long-term functional status of
      children with JPFS.

PMID- 9647452
TI  - Children's self-report of postoperative pain intensity and treatment threshold:
      determining the adequacy of medication.
AB  - OBJECTIVE: Many studies have shown indirectly that children are undermedicated
      for postoperative pain. In this study, we used a pain self-report scale to
      examine this more directly. METHODS: We performed a survey with 63 children who
      were postoperative from minor, uncomplicated surgery. Using the self-report
      scale, we determined the pain intensity at time of interview, the worst pain
      experienced postoperatively, and the intensity of pain that the subject felt to
      warrant pharmacologic intervention (the "treatment threshold"). A subgroup of 48
      children was asked to indicate on the scale the intensities that represented
      mild, moderate, and severe pain. RESULTS: Mean (SD) pain at time of interview was
      1.9 (1.7) on the 0-6 scale. Mean worst postoperative pain was 3.8 (1.8). The mean
      for treatment threshold was 3.2 (1.8). We found gender differences in regard to
      the judgments about the intensities representing mild, moderate, and severe pain,
      with girls rating these lower than did boys. Twenty-five percent of subjects
      reported pain that was mild, 29% reported moderate pain, and 46% reported severe
      pain. CONCLUSIONS: We found that 51% of subjects were undermedicated for
      postoperative pain, being required to suffer pain that was above their treatment
      threshold. By determining each subject's treatment threshold and estimate of
      moderate pain, we have better defined the intensity at which pain becomes
      clinically significant.

PMID- 9647453
TI  - Age as a factor in admission to chronic pain rehabilitation.
AB  - OBJECTIVE: To examine access to multidisciplinary pain rehabilitation programs
      for older patients. DESIGN: Telephone and written surveys of pain programs
      accredited by Commission on Accreditation of Rehabilitation Facilities. Visual
      Analog Scale (VAS) ratings of patient vignettes in which older patients were
      alternatively assigned their true age or a younger age. PARTICIPANTS: Health care
      professionals at pain programs. MAIN OUTCOME MEASURES: Telephone survey of
      admission policies and treatment services. VAS ratings of patient vignettes.
      RESULTS: No program excludes older pain patients by age. However, 28% of programs
      had admitted only the youngest old (< 70 years). Age-related criteria, such as
      presence of concurrent medical diagnoses that are more likely to exclude older
      patients, are common. In addition, VAS ratings of patient vignettes indicated an
      age bias: the same patients were rated as 14.8% less likely to be admitted (p <
      .001) and 12.5% less likely to succeed if admitted (p < .001) when their true,
      older age was given than when a false younger age was provided. CONCLUSION: Pain
      program admission policies do not exclude older patients by age but frequently
      include age-related criteria that disproportionately exclude the elderly. There
      is also evidence of an age bias in which age per se reduces perceived suitability
      for pain program admission.

PMID- 9647454
TI  - Spontaneous onset of back pain.
AB  - OBJECTIVES: To assess the frequency with which patients attribute low back pain
      to spontaneous onset. DESIGN: A consecutive sample of two distinct groups of
      patients seeking treatment for back pain: those without need to identify cause
      (study group, n = 4,689) and those required to report a specific event to qualify
      for benefits paid for by a third party (compensated group, n = 6,687). SETTING:
      Active exercise-based back pain rehabilitation clinics. SUMMARY OF BACKGROUND
      DATA: Research on the natural history of back pain has revealed frequent reports
      of spontaneous recovery, usually within 8-12 weeks after onset. There is little
      comparable literature pertaining to the report of spontaneous onset. METHODS:
      Data were collected for two groups of consecutive patients who attended for
      initial assessments of their back pain at 16 Canadian Back Institute locations,
      between May 1, 1994 and February 28, 1995. Patient responses were collected using
      a standardized, professionally administered questionnaire. RESULTS: In the group
      without need to identify cause, 66.7% of patients could not identify an event
      producing their symptoms. For those required to report a specific event, only
      9.8% of patients failed to attribute cause. Multivariate logistic regression
      revealed that the required-to-report group was approximately 15 times more likely
      to report an event (odds ratio = 14.95; 95% confidence interval = 13.44, 16.65)
      than the study group; those pursuing litigation were more than 2.5 times more
      likely to report a causative event (odds ratio = 2.68; 95% confidence interval =
      2.09, 3.49). CONCLUSIONS: Back pain occurred spontaneously in approximately 67%
      of patients seeking treatment in the study group. The authors consider
      spontaneous onset to be part of the natural history of back pain for this group.

PMID- 9647455
TI  - Transcutaneous electrical nerve stimulation in the treatment of chronic pain:
      predictive factors and evaluation of the method.
AB  - OBJECTIVE: Transcutaneous electrical nerve stimulation (TENS) is a widely used
      therapeutic approach in acute and chronic pain syndromes. The aim of this study
      was to investigate the influence of patient management as well as other factors
      on the outcome of TENS treatment. DESIGN: The study was carried out as a
      retrospective analysis of the course of treatment and the therapeutic results of
      transcutaneous electric nerve stimulation (TENS) in 482 patients with chronic
      pain of various origins. The follow-up period was up to 48 months. Two groups
      with differing patient management were compared. RESULTS: Competent patient
      evaluation and education (i.e., a long testing and learning phase as well as
      regular comprehensive after-care) was found to be important. Our analysis of the
      reasons for the discontinuation of long-term TENS therapy showed that the most
      important feature was the discrepancy between effort and therapeutic result.
      Other causes were intermittent depressive states and progression of the
      underlying disease followed by an aggravation of pain. In addition, numerous
      factors were identified that adversely affected the outcome of TENS treatment.
      These factors were listed in order of importance and were included in a
      prognostic score. CONCLUSIONS: The prognostic score permits an efficient
      selection of patients. Moreover, a comprehensive documentation of pain syndromes
      and their organic, psychogenic, and social features is presented. On the basis of
      this documentation, an appropriate therapeutic concept may be established. The
      prognostic score was validated in a subsequent study including 99 patients with
      chronic pain treated with TENS.

PMID- 9647456
TI  - Stressful life events and psychological dysfunction in Complex Regional Pain
      Syndrome type I.
AB  - OBJECTIVE: To determine to what extent stressful life events and psychological
      dysfunction play a role in the pathogenesis of Complex Regional Pain Syndrome
      type I (CRPS). DESIGN: A comparative study between a CRPS group and a control
      group. Stressful life events and psychological dysfunction evaluation was
      performed with a life event rating list and the Symptom Checklist-90 (SCL-90).
      SETTING: A university hospital. SUBJECTS: The CRPS group consisted of 24 patients
      with a history of upper extremity CRPS of less than 3 months. The control group
      consisted of 42 hand pathology patients waiting for elective hand surgery within
      the next 24 hours. MAIN OUTCOME MEASURES: Stressful life event rating was
      measured using the Social Readjustment Rating Scale. Psychological dysfunction
      was measured using the SCL-90. RESULTS: Stressful life events were experienced by
      19 patients (79.2%) in the CRPS group and by 9 patients (21.4%) in the control
      group. This difference was significant. Testing of psychological dysfunction (SCL
      90) in CRPS patients and the control group demonstrated some significant
      differences: male patients were more anxious than male controls; female patients
      were statistically more depressed, had feelings of inadequacy, and were
      emotionally less stable than female controls. In multivariate analysis, no
      significant differences were found across gender, age, or gender x group
      interactions. Of the SCL-90 dimensions, only insomnia correlated with the
      experienced stressful life events. CONCLUSION: Stressful life events are more
      common in the CRPS group, which indicates that there may be a multiconditional
      model of CRPS. The experience of stressful life events besides trauma or surgery
      are risk factors, not causes, in such a model.

PMID- 9647457
TI  - Symptoms of spinal stenosis do not improve after epidural steroid injection.
AB  - OBJECTIVE: This study was carried out to evaluate the therapeutic effect of
      epidural steroid injection on pseudoclaudication in patients with lumbar
      degenerative spinal canal stenosis. DESIGN: Fifty-three patients who complained
      of pseudoclaudication of less than 20 m in walking distance were randomly divided
      into three groups. Group 1 (n = 16) underwent epidural injection with 8 ml of
      saline. Group 2 (n = 18) underwent epidural block with 8 ml of 1% mepivacaine.
      Group 3 (n = 19) underwent epidural block with a combination of 8 ml of 1%
      mepivacaine and 40 mg of methylprednisolone. The criteria of evaluation were as
      follows: excellent effect, > 100 m in walking distance; good effect, 20-100 m in
      walking distance; poor effect, <20 m in walking distance. RESULTS: In group 1,
      the numbers of patients who showed a good effect were two (12.5%) after 1 week,
      one (6.5%) after 1 month, and one (6.5%) after 3 months. In group 2, the numbers
      of patients who showed a good or excellent result were 10 (55.5%) after 1 week,
      three (16.7%) after 1 month, and one (5.6%) after 3 months. In group 3, the
      numbers of patients who showed a good or excellent result were 12 (63.2%) after 1
      week, three (15.8%) after 1 month, and one (5.3%) after 3 months. There was no
      significant difference in the effectiveness of treatment between group 2 and
      group 3 throughout the time course. CONCLUSION: The results suggest that epidural
      steroid injection has no beneficial effect on the pseudoclaudication associated
      with spinal canal stenosis as compared with epidural block with a local
      anesthetic alone.

PMID- 9647458
TI  - Chest tube insertion: a prospective evaluation of pain management.
AB  - OBJECTIVE: To evaluate pain associated with chest tube insertion in a group of
      patients with malignant pleural effusions. DESIGN: Prospective case series.
      SETTING: Acute care cancer center in an academic institution. PATIENTS: Fifty-two
      patients with symptomatic malignant pleural effusions. Twenty-six evaluated by
      conventional approach to chest tube insertion (group 1), 26 evaluated after
      institution of a new chest tube protocol (group 2). INTERVENTIONS: A new protocol
      was designed to improve pain control during chest tube insertion. The protocol
      included improved housestaff and nursing education, premedication, proper
      insertion techniques, and more liberal and precise delivery of local anesthetic.
      OUTCOME MEASURES: Both groups were evaluated by a verbal self-report scale (1-10)
      to assess pain and anxiety. RESULTS: The mean pain rating in group 1 was 6.2 (+/
      0.76) compared with 3.7 (+/-5.6) in group 2 (p < 0.01). In group 1, pain or
      anxiety was 9 or 10 in 12 of 26 on a scale of 1 to 10, compared with 2 of 26 in
      group 2 (p < 0.001). Anxiety rating was 4.5 (+/-0.72) in group 1 compared with
      1.5 (+/-0.54) in group 2 (p < 0.01). CONCLUSIONS: Chest tube insertion was
      associated with an unacceptably high level of pain and anxiety in our hospital. A
      new protocol, including housestaff education and changes in nursing policies,
      technical aspects, local anesthetic dose and delivery, and pre-medication,
      allowed us to approach the goal of a painless chest tube insertion.

PMID- 9647459
TI  - Complex Regional Pain Syndromes: guidelines for therapy.
AB  - This report aims to present an orderly approach to the treatment of Chronic
      Regional Pain Syndrome (CRPS) types I and II through an algorithm. The central
      theme is functional restoration: a coordinated but progressive approach that
      introduces each of the treatment modalities needed to achieve both remission and
      rehabilitation. Reaching objective and measurable rehabilitation goals is an
      essential element. Specific exercise therapy to reestablish function after
      musculoskeletal injury is central to this functional restoration. Its application
      to CRPS is more contingent on varying rates of progress that characterize the
      restoration of function in patients with CRPS. Also, the various modalities that
      may be used, including analgesia by pharmacologic means or regional anesthesia or
      the use of neuromodulation, behavioral management, and the qualitatively
      different approaches that are unique to the management of children with CRPS, are
      provided only to facilitate functional improvement in a stepwise but methodical
      manner. Patients with CRPS need an individual approach that requires extreme
      flexibility. This distinguishes the management of these conditions from other
      well-described medical conditions having a known pathophysiology. In particular,
      the special biopsychosocial factors that are critical to achieving a successful
      outcome are emphasized. This algorithm is a departure from the contemporary
      heterogeneous approach to treatment of patients with CRPS. The underlying
      principles are motivation, mobilization, and desensitization facilitated by the
      relief of pain and the use of pharmacologic and interventional procedures to
      treat specific signs and symptoms. Self-management techniques are emphasized, and
      functional rehabilitation is the key to the success of this algorithm.

PMID- 9647460
TI  - Hypnosis after an adverse response to opioids in an ICU burn patient.
AB  - OBJECTIVE: Burn injuries produce severe wound care pain that is ideally
      controlled on intensive burn care units with high-dosage intravenous opioid
      medications. We report a case illustrating the use of hypnosis for pain
      management when one opioid medication was ineffective. SETTING: Intensive burn
      care unit at a regional trauma center. PATIENT: A 55-year-old man with an
      extensive burn suffered from significant respiratory depression from a low dosage
      of opioid during wound care and also experienced uncontrolled pain. INTERVENTION:
      Rapid induction hypnotic analgesia. OUTCOME MEASURES: Verbal numeric pain scale,
      and pain and anxiolytic medication usage. RESULTS: The introduction of hypnosis,
      supplemented by little or no opioids, resulted in excellent pain control, absence
      of need for supplemental anxiolytic medication, shortened length of wound care,
      and a positive staff response over a 14-day period. CONCLUSIONS: This case
      illustrates that hypnosis can not only be used easily and quite appropriately in
      a busy medical intensive care unit environment, but that sometimes this treatment
      may be a very useful alternative when opioid pain medication proves to be
      dangerous and ineffective. This case also illustrates possible clinical
      implications both pain relief and side-effect profiles for opioid receptor
      specificity. Although this report does not provide data regarding hypnotic
      mechanisms, it is clear that with some patients nonopioid inhibitory mechanisms
      can be activated in a highly effective manner, that clinical context may be
      important for the activation of those pathways, and that those mechanisms may be
      accessed more easily than opioid mechanisms.

PMID- 9647461
TI  - Cerebrospinal fluid pressure and acetazolamide treatment in idiopathic low back
      pain.

PMID- 9647462
TI  - Curcumin attenuation of acute adriamycin myocardial toxicity in rats.
AB  - The protective effect of curcumin on acute adriamycin (ADR) myocardial toxicity
      was analysed in rats. ADR toxicity, induced by a single intraperitoneal injection
      (30 mg kg(-1)), was revealed by elevated serum creatine kinase (CK) and lactate
      dehydrogenase (LDH). The level of the lipid peroxidation products, conjugated
      dienes and malondialdehyde, was markedly elevated by ADR. ADR caused a decrease
      in myocardial glutathione content and glutathione peroxidase activity. In
      contrast, cardiac catalase activity was increased in ADR rats. Curcumin treatment
      (200 mg kg(-1), seven days before and two days following ADR) significantly
      ameliorated the early manifestation of cardiotoxicity (ST segment elevation and
      an increase in heart rate) and prevented the rise in serum CK and LDH exerted by
      ADR. ADR rats that received curcumin displayed a significant inhibition of lipid
      peroxidation and augmentation of endogenous antioxidants. These results suggest
      that curcumin inhibits ADR cardiotoxicity and might serve as novel combination
      chemotherapeutic agent with ADR to limit free radical-mediated organ injury.

PMID- 9647463
TI  - Molecular cloning and characterization of rat P2Y4 nucleotide receptor.
AB  - An intronless open reading frame encoding a protein (361aa in length) was
      isolated from a rat genomic library probed with a DNA fragment from rat heart.
      This protein showed 83% sequence identity with the human P2Y4 (hP2Y4) receptor
      and represents a homologue of the human pyrimidinoceptor. However, the rP2Y4
      receptor is not selective for uridine nucleotides and, instead, shows an agonist
      potency order of ITP = ATP = ADP(pure) = UTP = ATPgammaS = 2-MeSATP = Ap4A >
      UDP(pure). ADP, ATPgammaS, 2-MeSATP and UDP are partial agonists. Thus, in terms
      of agonist profile, rP2Y4 is more like the P2U receptor subtype. The rP2Y4
      receptor was reversibly antagonized by Reactive blue 2 but not by suramin which,
      otherwise, inhibits the hP2Y2 receptor (a known P2U receptor). Thus, rP2Y4 and
      the P2Y2 subtype appear to be structurally distinct forms of the P2U receptor
      (where ATP and UTP are equi-active) but can be distinguished as suramin
      insensitive and suramin-sensitive P2U receptors, respectively.

PMID- 9647464
TI  - Effects of steroid treatment on activation of nuclear factor kappaB in patients
      with inflammatory bowel disease.
AB  - Nuclear factor kappB (NFkappaB) is a transcription factor that controls several
      genes important for immunity and inflammation. The aim of this study was to
      assess if activation of NFkappaB plays a role in the pathogenesis of inflammatory
      bowel disease (IBD), and whether steroid treatment affects NFkappaB activation.
      Activation of NFkappaB was analysed in colon biopsy samples of 13 patients with
      active IBD (8 Crohn's colitis, 5 ulcerative colitis) by electrophoretic mobility
      shift assays, under basal conditions and 3 weeks after treatment with 0.75 mg kg(
      1) day(-1) prednisolone. The presence of interleukin-8 mRNA in biopsies was
      assessed by RT-PCR. A specific NFkappaB band was present in all nuclear extracts
      from inflamed mucosa, whereas the band was barely detectable in uninflamed
      colonic mucosa. NFkappaB bands were super-shifted by antibodies against p50
      subunit, whereas antibodies against p65, p52, c-Rel, or Rel B did not modify the
      mobility of the band. Increased interleukin-8 mRNA was detected at the same sites
      of NFkappaB activation. Steroid-induced healing of colonic inflammation was
      associated with disappearance of NFkappaB from nuclear extracts. These results
      support the notion that NFkappaB plays an important role in the pathogenesis of
      IBD, and that blockade of NFkappaB activation is one of the mechanisms by which
      steroids suppress the inflammatory cascade in IBD.

PMID- 9647465
TI  - Different actions of CCK on pancreatic and gastric growth in the rat: effect of
      CCK(A) receptor blockade.
AB  - 1. It is now well established that cholecystokinin (CCK) has a major
      physiological role in the regulation of pancreatic secretion and gastro
      intestinal (GI) motility. Both these actions are mediated by stimulation of
      CCK(A)-receptors located on pancreatic acini and GI smooth muscle cells. While
      chronic administration of CCK-like peptides invariably causes pancreatic
      hypertrophy and hyperplasia, their action on gastric growth remains
      controversial. 2. In the present investigation the action of exogenous and
      endogenous CCK on both pancreatic and gastric growth was studied in the same
      animal. In addition, the ability of dexloxiglumide, a new potent and selective
      CCK(A)-receptor antagonist, to counteract CCK-mediated effects was evaluated. 3.
      The amphibian peptide caerulein (1 microg kg(-1) intraperitoneally three times
      daily) was used as a CCK agonist, while camostate (200 mg kg(-1) intragastrically
      once daily), a synthetic protease inhibitor, was used to release endogenous CCK.
      They were administered to rats for seven days with or without dexloxiglumide (25
      mg kg(-1) subcutaneously 15 min before the stimulus). On the eighth day, animals
      were killed, the pancreas and stomach excised, weighed, homogenized and their
      protein and DNA content measured. 4. Both exogenous and endogenous CCK increased
      the weight of the pancreas as well as the total pancreatic protein and DNA
      content. Dexloxiglumide, which alone did not affect pancreatic size and
      composition, was able to counteract both caerulein- and camostate-induced
      pancreatic changes. Neither stimuli affected gastric growth in respect of weight
      and composition of the oxyntic gland area and the antrum. 5. These results show
      different effects of CCK on pancreatic and gastric growth. The CCK-induced
      pancreatic hypertrophy and hyperplasia are blocked by the potent and specific
      CCK(A)-receptor antagonist, dexloxiglumide. This compound therefore represents a
      useful tool to investigate CCK-receptor interactions in peripheral organs.

PMID- 9647466
TI  - Pharmacological characterization of a nonpeptide bradykinin B2 receptor
      antagonist, FR165649, and agonist, FR190997.
AB  - 1. The nonpeptide bradykinin (BK) B2 receptor antagonist, FR165649 (8-[2,6
      dichloro-3-[N-[(E)-4-(N-methylcarbamoyl)cinnamidoacetyl ]-N
      methylamino]benzyloxy]-2-methylquinoline), and agonist, FR190997 (8-[2,6-dichloro
      3-[N-[(E)-4-(N-methylcarbamoyl) cinnamidoacetyl]-N-methylamino]benzyloxy]-2
      methyl-4-(2-pyridyl methoxy)quinoline) have been identified. These compounds have
      a common chemical structure, and the 2-pyridylmethoxy group is the only
      structural difference between them. 2. Both FR165649 and FR190997 displaced [3H]
      BK binding to B2 receptors in guinea-pig ileum membranes, with an IC50 of 4.7 x
      10(-10) M and 1.5 x 10(-9) M, respectively. They also displaced [3H]-BK binding
      to B2 receptors in human lung fibroblast IMR-90 cells, with an IC50 of 1.6 x 10(
      9) M and 9.8 x 10(-10) M, respectively. 3. In guinea-pig isolated ileum
      preparations, FR165649 had no agonistic effect on contraction and caused parallel
      rightward shifts of the concentration-response curves to BK on contraction.
      Analysis of the data produced a nominal pA2 value of 9.2+/-0.1 (n=5) and a slope
      of 1.4+/-0.1 (n=5). On the other hand, FR190997 induced concentration-dependent
      contraction of guinea-pig ilea with a pD2 of 7.9+/-0.2 and the contraction was
      inhibited by a specific peptide bradykinin B2 receptor antagonist, Hoe 140 (D-Arg
      [Hyp3, Thi5, D-Tic7, Oic8]BK) in a non-competitive manner. 4. In IMR-90 cells,
      FR165649 had no agonistic effect on phosphatidyl inositol (PI) hydrolysis and
      caused parallel rightward shifts (approximately 200 fold shift at 10(-7) M) of
      the concentration-response curves to BK on PI hydrolysis. FR190997 induced
      concentration-dependent PI hydrolysis in IMR-90 cells with a pD2 of 8.4+/-0.1,
      and this effect was inhibited by Hoe 140. 5. These results indicate that FR165649
      and FR190997 are, respectively, a potent bradykinin B2 receptor antagonist and
      agonist, and that the agonistic activity depends on the small part of the
      nonpeptide ligand. FR165649 and FR190997 may be useful tools for studying the
      relationship between ligands and receptors.

PMID- 9647467
TI  - Role of reactive oxygen species in the signalling cascade of cyclosporine A
      mediated up-regulation of eNOS in vascular endothelial cells.
AB  - 1. Cyclosporine A (CsA) increases eNOS mRNA expression in bovine cultured aortic
      endothelial cells (BAEC). As some effects of CsA may be mediated by reactive
      oxygen species (ROS), present experiments were devoted to test the hypothesis
      that the CsA-induced eNOS up-regulation could be dependent on an increased
      synthesis of ROS. 2. CsA induced a dose-dependent increase of ROS synthesis, with
      the two fluorescent probes used, DHR123 (CsA 1 microM: 305+/-7% over control) and
      H2DCFDA (CsA 1 microM: 178+/-6% over control). 3. Two ROS generating systems,
      xanthine plus xanthine oxidase (XXO) and glucose oxidase (GO), increased the
      expression of eNOS mRNA in BAEC, an effect which was maximal after 8 h of
      incubation (XXO: 168+/-21% of control values. GO: 208+/-18% of control values).
      The ROS-dependent increased eNOS mRNA expression was followed by an increase in
      eNOS activity. 4. The effect of CsA on eNOS mRNA expression was abrogated by
      catalase, and superoxide dismutase (SOD). In contrast, the antioxidant PDTC
      augmented eNOS mRNA expression, both in basal conditions and in the presence of
      CsA. 5. The potential participation of the transcription factor AP-1 was
      explored. Electrophoretic mobility shift assays were consistent with an increase
      in AP-1 DNA-binding activity in BAEC treated with CsA or glucose oxidase. 6. The
      present results support a role for ROS, particularly superoxide anion and
      hydrogen peroxide, as mediators of the CsA-induced eNOS mRNA up-regulation.
      Furthermore, they situate ROS as potential regulators of gene expression in
      endothelial cells, both in physiological and pathophysiological situations.

PMID- 9647468
TI  - Activation of midbrain presumed dopaminergic neurones by muscarinic cholinergic
      receptors: an in vivo electrophysiological study in the rat.
AB  - 1. Extracellular single-unit recording and iontophoresis were used to examine the
      effects of different cholinoceptor agonists and antagonists on the firing rate
      and firing pattern of A9 and A10 presumed dopaminergic neurones in the
      anaesthetized rat. 2. Administration of low currents (1-5 nA) of the selective
      muscarinic agonists oxotremorine M (Oxo M) and muscarine and of the non-selective
      muscarinic/nicotinic agonist carbamylcholine (CCh) produced a dose-dependent
      increase in firing rate in most of the A9 and A10 presumed dopaminergic neurones
      tested. Oxo M-induced activation could be completely blocked by iontophoretic
      application of the muscarinic antagonist butyl-scopolamine or systemic
      administration of the muscarinic antagonist scopolamine (300 microg kg(-1),
      i.v.). 3. Iontophoretic application of the selective nicotinic agonist
      methylcarbamylcholine (MCCh), but not nicotine, induced a consistent increase in
      firing rate. Surprisingly, the excitatory effect of MCCh was significantly
      reduced by the selective muscarinic antagonist scopolamine (300 microg kg(-1),
      i.v.), but not by the selective nicotinic antagonist mecamylamine (2.2 mg kg(-1),
      i.v.). Mecamylamine (3 mg kg(-1), i.v.) was also ineffective in reducing the CCh
      induced activation of presumed dopamine neurones, suggesting that both CCh and
      MCCh increased the activity of dopamine neurones via an interaction with
      muscarinic receptors. 4. Iontophoretic application of the endogenous agonist
      acetylcholine (ACh) had no or little effect on the firing activity of A10
      presumed dopaminergic neurones. However, concomitant application of neostigmine,
      a potent cholinesterase inhibitor, with acetylcholine induced a substantial
      activation of these neurones. This activation consisted of two components; one,
      which was prevalent, was scopolamine (300 microg kg(-1), i.v.)-sensitive, and the
      other was mecamylamine (2 mg kg(-1), i.v.)-sensitive. 5. In addition to their
      effect on firing activity, Oxo M, muscarine and concomitant neostigmine/ACh
      caused a significant increase in burst firing of A10 neurones, but not of A9
      neurones. 6. These data suggest that dopamine cells, both in the A9 and A10
      regions, possess functional muscarinic receptors, the activation of which can
      increase their firing rate and, for A10 neurones, their amount of burst activity.
      These cholinoceptors would be able to influence the activity of the midbrain
      dopamine system greatly and may play a role in, and/or be a therapeutic target
      for, brain disorders in which dopamine is involved (e.g., Parkinson's disease,
      drug addiction and schizophrenia).

PMID- 9647469
TI  - Ruthenium red as an effective blocker of calcium and sodium currents in guinea
      pig isolated ventricular heart cells.
AB  - 1. The effect of ruthenium red on calcium and sodium currents was studied in
      guinea-pig isolated ventricular heart cells with the whole cell patch-clamp
      technique. 2. Ruthenium red very efficiently blocked the L-type calcium current
      in a dose-dependent manner. A significant block was observed for concentrations
      as low as 0.3 microM. Analysis of the dose-response curve with the logistic
      equation indicated an EC50 of 0.8 microM, a maximum inhibition of 85% reached at
      5 microM, and a coefficient of 2.37. 3. There was no shift in the voltage
      dependence of the Ca current activation, nor in that of its steady-state
      inactivation determined with a 1 s prepulse. However, removal of Ca current
      inactivation at positive voltage was considerably reduced in the presence of
      concentrations of ruthenium red above 1 microM. A slowing of the time-course of
      inactivation of the Ca current was also observed. 4. At 10 microM, a
      concentration generally used to block the sarcoplasmic Ca release channels or the
      mitochondrial Ca uptake, ruthenium red blocked 26.7+/-4.3% (n=8) of the sodium
      current, and slowed its inactivation time-course. No effect was observed on the
      voltage-dependence of the current activation or inactivation. The peak sodium
      current was also decreased at a 10 times lower concentration by 7.6+/-2.7% (n=3).
      5. Thus, at concentrations used to assess intracellular Ca movements, ruthenium
      red induced in heart cells a significant block of both Ca and Na channels.

PMID- 9647470
TI  - Effect of clenbuterol on non-endothelial nitric oxide release in rat mesenteric
      arteries and the involvement of beta-adrenoceptors.
AB  - 1. The aim of the present study was to explore the contribution of adrenergic,
      sensory and nitrergic innervations to the inhibitory effects of the beta2
      adrenoceptor agonist clenbuterol on responses to electrical field stimulation
      (EFS, 200 mA, 0.3 ms, 1-16 Hz, for 30 s, at 1 min interval) in rat mesenteric
      artery segments without endothelium and the possible involvement of adrenergic,
      sensory and nitrergic innervations. 2. Clenbuterol (1 microM) reduced EFS-induced
      contractile responses, and this effect was reversed by the beta-antagonist
      propranolol (1 microM) (contraction at 16 Hz expressed as % of 75 mM K+-induced
      contraction was: control, 69+/-9, clenbuterol, 31+/-6, n=13, P<0.001; control,
      83+/-5, clenbuterol+propranolol 70+/-7, n=11, P>0.05). 3. In arteries
      preincubated with [3H]-noradrenaline (NA), clenbuterol did not modify the tritium
      overflow evoked by EFS (200 mA, 0.3 ms, 4 Hz, for 60 s; ratio between tritium
      release in the second and first stimuli was: control, 0.80+/-0.05 and clenbuterol
      added before second stimulus, 0.91+/-0.11, n=5, P>0.05). 4. The nitric oxide (NO)
      synthase inhibitors NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine
      methyl ester (L-NAME) (10 and 100 microM), and the guanylate cyclase inhibitor
      methylene blue (10 microM) increased the contractions caused by EFS (%
      contraction at 16 Hz, control, 81+/-7, n=26; 10 microM L-NMMA, 109+/-12, n=8,
      P<0.05; methylene blue, 119+/-6, n=6, P<0.05). However, these contractions were
      decreased by the NO synthase substrate L-arginine 10 microM (14+/-6%, n=6,
      P<0.001), but not modified by either the sensory neurones toxin capsaicin (0.5
      microM, 75+/-6%, n=6, P>0.05) or the protein synthesis inhibitor cycloheximide
      (10 microM, 83+/-6%, n=8, P>0.05). None of these drugs altered the concentration
      response curves to exogenous NA (n=7). 5. Pretreatment with capsaicin or
      cycloheximide did not modify the reduction of the EFS-evoked contraction provoked
      by clenbuterol. However the presence of L-NMMA (or L-NAME) or methylene blue did
      decrease the effect of clenbuterol (% contraction at 16 Hz, clenbuterol, 31+/-6,
      n=13; clenbuterol+10 microM L-NMMA, 93+/-11, n=8, P<0.05; clenbuterol+methylene
      blue, 90+/-7, n=6, P<0.05). 6. These results suggest that the reduction caused by
      clenbuterol in the contraction induced by EFS in rat mesenteric arteries seems to
      be mediated by NO release, through the activation of beta2-adrenoceptors probably
      present on nitrergic nerves.

PMID- 9647471
TI  - Role of hyperthermia in the protective action of clomethiazole against MDMA
      ('ecstasy')-induced neurodegeneration, comparison with the novel NMDA channel
      blocker AR-R15896AR.
AB  - 1. The immediate effect of administration of 3,4-methylenedioxymethamphetamine
      (MDMA or 'ecstasy') on rectal temperature and the effect of putative
      neuroprotective agents on this change has been examined in rats. The influence of
      the temperature changes on the long term MDMA-induced neurodegeneration of
      cerebral 5-hydroxytryptamine (5-HT) nerve terminals was also examined. 2. The
      novel low affinity N-methyl-D-aspartate (NMDA) receptor channel blocker AR
      R15896AR (20 mg kg(-1), i.p.) given 5 min before and 55 min after MDMA (15 mg kg(
      1), i.p.) did not prevent the MDMA-induced hyperthermia and did not alter either
      the MDMA-induced neurodegenerative loss of 5-HT and 5-hydroxyindoleacetic acid (5
      HIAA) in cortex, striatum and hippocampus or loss of [3H]-paroxetine binding in
      cortex 7 days later. 3. The neuroprotective agent clomethiazole (50 mg kg(-1),
      i.p.) given 5 min before and 55 min after MDMA (15 mg kg(-1)) abolished the MDMA
      induced hyperthermic response and markedly attenuated the loss of 5-HT, 5-HIAA
      and [3H]-paroxetine binding in the brain regions examined 7 days later. 4. When
      rats treated with MDMA plus clomethiazole were kept at high ambient temperature
      for 5 h post-MDMA, thereby keeping their body temperature elevated to near that
      seen in rats given MDMA alone, the MDMA-induced loss of 5-HT, 5-HIAA and [3H]
      paroxetine was still attenuated. However, the protection (39%) afforded by the
      clomethiazole administration was less than seen in rats kept at normal ambient
      temperature (75%). 5. These data support the proposals of others that NMDA
      receptor antagonists are neuroprotective against MDMA-induced degeneration only
      if they induce hypothermia and further suggest that increased glutamate activity
      may not be involved in the neurotoxic action of MDMA. 6. These data further
      demonstrate that a proportion of the neuroprotective action of clomethiazole is
      due to an effect on body temperature but that, in addition, the compound protects
      against MDMA-induced damage by an unrelated mechanism.

PMID- 9647472
TI  - Pharmacological characterization of the human melatonin Mel1a receptor following
      stable transfection into NIH3T3 cells.
AB  - 1. Mouse fibroblasts (NIH3T3) transfected with the full-length coding region of
      the Mel1a melatonin receptor stably expressed the receptor, coupled to a
      pertussis toxin-sensitive G-protein(s) and exhibiting high affinity and adequate
      pharmacological profile. 2. The receptor protein had the tendency of a strong
      coupling to the G-protein and therefore low-affinity state was induced by
      uncoupling the receptor from its G-protein in presence of high concentrations of
      NaCl (500-700 mM) and/or GTPgammaS (100 microM). Thereafter, the affinity of a
      series of melatonin analogues was determined to both, high- and low-affinity
      receptor states, thus providing a basis for the prediction of their efficacy,
      according to the ternary complex model. 3. The cells were subsequently used to
      study the agonist-induced G-protein activation, determined by calculating the
      rate of GDP-GTP exchange measured in presence of 35S-labelled GTPgammaS. The
      natural ligand melatonin induced a significant increase in the GDP-GTP exchange
      rate, the presence of GDP and NaCl being necessary to observe this effect. 4. The
      full agonists 2-phenylmelatonin, 2-bromomelatonin and 6-chloromelatonin equally
      induced an increase of the GDP-GTP exchange. 5-Hydroxy-N-acetyltryptamine
      activated the GTP-GDP exchange to a much lesser extent (53%) than melatonin, thus
      behaving as a partial agonist. As predicted by the model, the melatonin
      antagonist (N-[(2-phenyl-1H-indol-3-yl)ethyl]cyclobutanecarboxamide) was without
      effect on basal G protein activation. Coincubation of this compound with
      melatonin induced a dose-dependent rightward shift in the melatonin concentration
      effect curve, thus exhibiting the behaviour of a competitive and surmountable
      antagonist. 5. Using the equation proposed by Venter (1997) we were able to
      determine that there were no 'spare' receptors in the system. Therefore, the
      approach proposed in the present work can be successfully used for the
      determination of 'drug action' at the level of the human Mel1a melatonin receptor
      and evaluation of the efficacy of new selective melatonin analogues.

PMID- 9647473
TI  - Effects of tumour necrosis factor-alpha on the coronary circulation of the rat
      isolated perfused heart: a potential role for thromboxane A2 and sphingosine.
AB  - 1. The actions of tumour necrosis factor-alpha (TNF-alpha) on the coronary
      circulation were investigated in the rat isolated heart, perfused under constant
      flow, recirculating conditions. 2. An early increase in coronary perfusion
      pressure (CPP) was observed upon treatment with TNF-alpha (increase in CPP 10 min
      after TNF-alpha treatment: 45+/-12 mmHg vs control: 15+/-4 mmHg, P<0.05). The
      role of sphingosine, prostanoids and endothelins, in this coronary constrictor
      action, was investigated with the use of pharmacological inhibitors and
      antagonists. 3. The TNF-alpha induced increase in coronary tone was blocked by
      indomethacin, 10 microM (increase in CPP after 10 min: 13+/-4 mmHg vs TNF-alpha
      alone, P<0.05). 4. The thromboxane receptor antagonist GR32191, 10 microM,
      attenuated the TNF-alpha induced coronary constriction (12+/-2 mmHg vs TNF-alpha
      alone, P<0.05), as did the joint thromboxane A2 synthesis inhibitor and receptor
      antagonist ZD1542, 10 microM (8+/-1 mmHg vs TNF-alpha alone, P<0.05). 5. The
      ceramidase inhibitor N-oleoylethanolamine (NOE), 1 microM, also blocked the TNF
      alpha induced response (8+/-4 mmHg vs TNF-alpha alone, P<0.05). 6. In contrast,
      the coronary constrictor action of TNF-alpha was not inhibited by the
      endothelinA/B receptor antagonist bosentan, 3 microM (38+/-9 mmHg vs TNF-alpha,
      P=NS). 7. These data indicated that the early coronary vasoconstriction induced
      by TNF-alpha was mediated by both thromboxane A2 and sphingosine, suggesting an
      interaction between both the sphingomyelinase and phospholipase A2 metabolic
      pathways.

PMID- 9647474
TI  - Endothelin receptor subtypes and their functional relevance in human small
      coronary arteries.
AB  - 1. The potent constrictor peptide endothelin (ET) has been implicated in various
      cardiovascular disorders including myocardial infarction and atherosclerosis. We
      have investigated the nature of ET receptor subtypes present on human small
      coronary arteries. 2. Small coronary arteries were mounted in a wire-myograph for
      in vitro pharmacology. To investigate the ET receptor subtypes present in
      different segments of the coronary vascular tree, arteries were grouped according
      to internal diameter. Responses in arteries with small internal diameters (mean
      316.7+/-7.9 microm; Group B) were compared to those in larger arteries (mean
      586.2+/-23.1 microm; Group A). 3. ET-1 consistently and potently contracted
      arteries from Group A and B, with EC50 values of 1.7 (0.9-3.2) nM (n=15) and 2.3
      (1.4-4.2) nM (n=14), respectively. No correlation was observed between ET-1
      potency and internal diameter. The response to ET-1 was potently antagonized by
      the selective ET(A) receptor antagonist PD156707 in both Group A and Group B,
      yielding pA2 values of 8.60+/-0.12 (n=4-6) and 8.38+/-0.17 (n=4-6), respectively.
      Slopes from Schild regression were not significantly different from unity. 4. In
      contrast to ET-1, individual responses to ET-3 were variable. While all arteries
      from Group A responded to ET-3 (EC50 approximately 69 (23-210) nM) (n=12), no
      response was obtained in 5 of the 14 tested in Group B. Of those responding, many
      failed to reach a maximum at concentrations up to 1 microM. ET-1 was more potent
      than ET-3 in all arteries tested. A biphasic ET-3 response was observed in 8
      arteries suggesting that a small ET(B) population was also present in some
      patients. The selective ET(B) receptor agonist sarafotoxin S6c had little or no
      effect up to 10 nM (n=4-6). 5. Responses to ET-1 and ET-3 were unaffected by
      removal of the endothelium in arteries from both groups suggesting a lack of
      functional, relaxant ET(B) receptors on endothelial cells (n=5). 6. Using
      autoradiography, specific high density binding of the non-selective, ET(A)/ET(B)
      ligand [125I]-ET-1 and selective ET(A) ligand [125I]-PD151242 was detected on the
      vascular smooth muscle layer of small intramyocardial coronary arteries (n=5). In
      contrast, little or no binding of the selective ET(B) receptor ligand [125I]
      BQ3020 was observed (n=5). Similarly, [125I]-ET-1 binding to vascular smooth
      muscle was absent in the presence of the selective ET(A) receptor antagonist
      PD156707. 7. We conclude that human small epi- and intramyocardial coronary
      arteries express predominantly ET(A) receptors and it is these receptors which
      mediate ET-induced contractions. A constrictor ET(B) receptor population may
      exist in some patients. However, these receptors may have a limited role as
      contractions to ET-1 can be blocked fully by the selective ET(A) receptor
      antagonist PD156707.

PMID- 9647475
TI  - Depression of NMDA receptor-mediated synaptic transmission by four alpha2
      adrenoceptor agonists on the in vitro rat spinal cord preparation.
AB  - 1. Alpha2-adrenoceptor agonists have a spinal site of analgesic action. In the
      current study the synaptic depressant actions of xylazine, detomidine, romifidine
      and dexmedetomidine have been compared on segmental reflexes containing NMDA
      receptor-mediated components in the neonatal rat hemisected spinal cord
      preparation in vitro. 2. Reflexes were evoked in the ventral root following
      either supramaximal electrical stimulation of the corresponding ipsilateral
      lumbar dorsal root to evoke the high intensity excitatory postsynaptic potential
      (e.p.s.p.) involving all primary afferent fibres, or low intensity stimulation to
      evoke the solely A fibre-mediated low intensity e.p.s.p. The high intensity
      e.p.s.p. contains a greater NMDA receptor-mediated component. 3. Xylazine,
      romifidine, detomidine and dexmedetomidine all depressed both the high intensity
      e.p.s.p. and the low intensity e.p.s.p. giving respective EC50 values of 0.91+/
      0.2 microM (n=12), 23.4+/-3 nM (n=12), 37.7+/-7 nM (n=8) and 0.84+/-0.1 nM (n=4)
      for depression of the high intensity e.p.s.p. and 0.76+/-0.1 microM (n=12),
      22.0+/-3 nM (n=12), 24.9+/-6 nM (n=4) and 2.7+/-0.6 nM (n=4) for depression of
      the low intensity e.p.s.p., respectively. Unlike the other three drugs, the two
      values for dexmedetomidine, showing a greater selectivity for the high intensity
      e.p.s.p., are significantly different. 4. Each of these depressant actions was
      reversed by the selective alpha2-adrenoceptor antagonist atipamezole (1 microM).
      5. In contrast to previous reports of the actions of alpha2-adrenoceptor agonists
      on the in vitro spinal cord preparation, at concentrations ten fold higher than
      the above EC50 values xylazine, romifidine, detomidine and dexmedetomidine
      depressed the initial population spike of motoneurons (MSR). This depression was
      not reversed by atipamezole. 6. Comparison of the rank order of the present EC50
      values for depression of the high intensity e.p.s.p. with potency ratios from in
      vivo analgesic tests in previous studies show a close correlation between the
      present in vitro tests and analgesic potency. There is no correlation between the
      present data and previously obtained affinities of the agonists at non-adrenergic
      imidazoline binding sites. 7. The current findings therefore suggest that
      xylazine, romifidine, detomidine and dexmedetomidine are exerting their central
      analgesic actions at the spinal level principally through alpha2-adrenoceptors.
      All four agonists showed the same profile of selective depression of the NMDA
      receptor-mediated component of reflexes similar to that reported previously for
      clonidine. However dexmedetomidine, unlike the other ligands, selectively
      depressed the high intensity e.p.s.p.

PMID- 9647476
TI  - Characterization of prostanoid receptor-evoked responses in rat sensory neurones.
AB  - 1. Prostanoid receptor-mediated sensitization, or excitation, of sensory nerve
      fibres contributes to the generation of hyperalgesia. To characterize the
      prostanoid receptors present on sensory neurones, biochemical assays were
      performed on primary cultures of adult rat dorsal root ganglia (DRG) and the F-11
      (embryonic rat DRG x neuroblastoma hybrid) cell line. 2. In DRG cultures, the IP
      receptor agonists, cicaprost and carbaprostacyclin (cPGI2) stimulated cyclic AMP
      accumulation. Prostaglandin E2 (PGE2) also increased cyclic AMP levels, but to a
      lesser extent, while carbocyclic thromboxane A2 (cTxA2), PGD2 and PGF2alpha had
      negligible effects. The rank order of agonist potency was
      cicaprost>PGE2=BMY45778=cPGI2=PGI2. In the F-11 cells, the rank order of agonist
      potency for the stimulation of cyclic AMP accumulation was:
      cicaprost>iloprost=cPGI2=PGI2=BMY45778>PGE2=cTXA2++ +. In DRG cultures, cicaprost
      induced significantly more accumulation of inositol phosphates than PGE2. 3. To
      examine the effects of prostanoids on C-fibre activity, extracellular recordings
      of d.c. potentials from the rat isolated vagus nerve were made with the 'grease
      gap' technique. PGI2 (0.1 nM-10 microM) produced the largest depolarizations of
      the nerve. The rank order of agonist potency was:
      PGI2=cPGI2=PGE1>cTXA2>PGE2=PGD2=TXB2>PGF2alpha. 4. Prior depolarization of nerves
      with either forskolin (10 microM) or phorbol dibutyrate (1 microM) alone
      significantly reduced the response to PGI2 (10 microM), while simultaneous
      application of both forskolin and phorbol dibutyrate attenuated PGI2 responses
      almost completely. 5. Putative EP1 and/or TP receptor-selective antagonists had
      no effect on the responses to PGI2, cPGI2 or PGE2 in the three preparations
      studied. 6. Collectively, these data are consistent with a positive coupling of
      IP receptors to both adenylyl cyclase and phospholipase C in sensory neurones.
      These findings suggest that IP receptors play a major role in the sensitization
      of rat sensory neurones.

PMID- 9647477
TI  - No evidence for a significant non-nitrergic, hyperpolarising factor contribution
      to field stimulation-induced relaxation of the mouse anococcygeus.
AB  - 1. The aim of the study was to determine whether a nerve-derived hyperpolarizing
      factor (NDHF) might contribute to non-adrenergic, non-cholinergic (NANC)
      relaxations of the mouse anococcygeus when low concentrations of contractile
      agent are used to raise tone and low frequencies of field stimulation applied;
      such a non-nitrergic NDHF has been proposed to contribute to NANC relaxations of
      the rat anococcygeus and guinea-pig taenia coli. 2. Phenylephrine (0.1-100
      microM) produced concentration-related contractions of the mouse isolated
      anococcygeus muscle; 0.2 microM phenylephrine (EC26) was used to raise tone in
      subsequent experiments. 3. Field stimulation (0.5, 1.0 and 5.0 Hz) produced
      frequency-dependent relaxations of phenylephrine-induced tone. In the presence of
      the nitric oxide synthase inhibitor L-NG-nitro-arginine (L-NOARG; 100 microM),
      the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxodiazolo[4,3-a]quinoxalin-1
      one (ODQ; 5 microM), or a combination of these two drugs, relaxations to field
      stimulation were abolished at all frequencies studied. Relaxations to sodium
      nitroprusside (0.01-5 microM) were unaffected by L-NOARG but strongly inhibited
      by ODQ; neither enzyme inhibitor affected relaxations to 8-Br-cyclic GMP (10
      microM). 4. Nifedipine (1 microM) reduced the contractile response to 0.2 microM
      phenylephrine by 38%; however, it had no effect on NANC relaxations. 5. It is
      concluded that NANC relaxations of the mouse anococcygeus are purely nitrergic
      and that there is no significant contribution from a putative NDHF.

PMID- 9647478
TI  - Inhibition of the ATP-sensitive potassium channel from mouse pancreatic beta
      cells by surfactants.
AB  - 1. We have used patch-clamp methods to study the effects of the detergents,
      Cremophor, Tween 80 and Triton X100 on the K(ATP) channel in the pancreatic beta
      cell from mouse. 2. All three detergents blocked K(ATP) channel activity with the
      following order of potency: Tween 80 (Ki< approximately 83 nM)>Triton X100
      (Ki=350 nM)>Cremophor. In all cases the block was poorly reversible. 3. Single
      channel studies suggested that at low doses, the detergents act as slow blockers
      of the K(ATP) channel. 4. Unlike the block produced by tolbutamide, that produced
      by detergent was not affected by intracellular Mg2+-nucleotide, diazoxide or
      trypsin treatment, nor did it involve an acceleration of rundown or increase in
      ATP sensitivity of the chanel. 5. The detergents could block the pore-forming
      subunit, Kir6.2deltaC26, which can be expressed independently of SUR1 (the
      regulatory subunit of the K(ATP) channel). These data suggest that the detergents
      act on Kir6.2 and not SUR1. 6. The detergents had no effect on another member of
      the inward rectifier family: Kir1.1a (ROMK1). 7. Voltage-dependent K-currents in
      the beta-cell were reversibly blocked by the detergents with a far lower potency
      than that found for the K(ATP) channel. 8. Like other insulin secretagogues that
      act by blocking the K(ATP) channel, Cremophor elevated intracellular Ca2+ in
      single beta-cells to levels that would be expected to elicit insulin secretion.
      9. Given the role of the K(ATP) channel in many physiological processes, we
      conclude that plasma borne detergent may have pharmacological actions mediated
      through blockage of the K(ATP) channel.

PMID- 9647479
TI  - Nitric oxide and the haemodynamic profile of endotoxin shock in the conscious
      mouse.
AB  - 1. The release of cytokines following administration of endotoxin and the
      contribution of nitric oxide (NO) to the subsequent haemodynamic profile were
      investigated in the conscious mouse. 2. Administration of endotoxin (E. Coli,
      026:B6, 12.5 mg kg(-1), i.v.) elevated the concentration of tumour necrosis
      factor-alpha (TNF-alpha) in the plasma within 0.5 h, reaching a maximum at 2 h
      and returning to control concentrations by 4 h. In addition, the concentration of
      interleukin-6 (IL-6) in the plasma was also elevated within 1 h, reaching a
      maximum at 3 h and remaining elevated throughout the 12 h of study. 3. Endotoxin
      (12.5 mg kg(-1), i.v.) induced the expression of a Ca2+-independent (inducible)
      NO synthase in the mouse heart and elevated the concentrations of nitrite and
      nitrate in the plasma within 4 h, reaching a maximum at 12 h. This was
      accompanied by a progressive fall in blood pressure over the same period. 4. The
      vasopressor effect of noradrenaline (0.5-4 microg kg(-1) min(-1), i.v.)
      administered as a continuous infusion was significantly attenuated 7 h after
      endotoxin (12.5 mg kg(-1), i.v). 5. The NO synthase inhibitor NG-monomethyl-L
      arginine HCl (L-NMMA; 1-10 mg kg(-1), i.v. bolus) reversed the fall in blood
      pressure when administered 7 h after endotoxin (12.5 mg kg(-1), i.v.). 6. In an
      attempt to maintain a constant blood concentration, L-NMMA was administered as a
      continuous infusion (10 mg kg(-1) h(-1), i.v.), beginning 4 h after a lower dose
      of endotoxin (6 mg kg(-1), i.v.). Such treatment prevented the fall in blood
      pressure and the elevation of nitrite and nitrate in the plasma throughout the 18
      h of observation. 7. The fall in blood pressure following endotoxin (3 mg kg(-1),
      i.v.) was significantly reduced throughout the 18 h of observation in homozygous
      mutant mice lacking the inducible NO synthase. 8. In summary, we have developed a
      model of endotoxin shock in the conscious mouse in which an overproduction of NO
      by the inducible NO synthase is associated with the haemodynamic disturbances.
      This model, which exhibits many of the characteristics of septic shock in man,
      will enable the study of the pathology of this condition in more detail and aid
      the investigation of potential therapeutic agents both as prophylactics and, more
      importantly, as treatments.

PMID- 9647480
TI  - Effect of rolipram and dibutyryl cyclic AMP on resequestration of cytosolic
      calcium in FMLP-activated human neutrophils.
AB  - 1. We have investigated the effects of the selective phosphodiesterase (PDE) type
      4 inhibitor, rolipram (0.01-1 microM) on cytosolic Ca2+ fluxes in FMLP-activated
      human neutrophils, as well as on superoxide production by, and release of
      elastase from, these cells. 2. Cytosolic Ca2+ fluxes were measured by use of fura
      2 spectrofluorimetry in combination with a radiometric procedure that enables
      distinction between net efflux and influx of the cation. Superoxide production
      and elastase release were measured by lucigenin-enhanced chemiluminescence and a
      colorimetric procedure, respectively. 3. Pretreatment of neutrophils with
      rolipram did not affect the FMLP-activated release of Ca2+ from intracellular
      stores, but was associated with dose-related acceleration of the rate of decline
      in fura-2 fluorescence and with decreased efflux, as well as store-operated
      influx of 45Ca2+, indicative of enhancement of resequestration of the cation by
      the endo-membrane Ca2+-ATPase. 4. Inhibition of superoxide production and
      elastase release was observed at concentrations of rolipram which accelerated the
      clearance of Ca2+ from the cytosol of FMLP-activated neutrophils. 5. These
      effects of rolipram on FMLP-activated Ca2+ fluxes, superoxide generation and
      elastase release were mimicked by pretreatment of neutrophils with dibutyryl
      cyclic AMP (0.5-4 mM), while theophylline (10-150 microM), a non-specific PDE
      inhibitor, as well as the beta2-agonist, salbutamol, were less effective. 6. We
      conclude that rolipram deactivates FMLP-stimulated human neutrophils by
      enhancement of cyclic AMP-dependent resequestration of cytosolic Ca2+.

PMID- 9647481
TI  - Characterization of Ro 04-6790 and Ro 63-0563: potent and selective antagonists
      at human and rat 5-HT6 receptors.
AB  - 1. This study describes the in vitro characterization of two potent and selective
      5-HT6 receptor antagonists at the rat and human recombinant 5-HT6 receptor. 2. In
      binding assays with [3H]-LSD, 4-amino-N-(2,6 bis-methylamino-pyrimidin-4-yl)
      benzene sulphonamide (Ro 04-6790) and 4-amino-N-(2,6 bis-methylamino-pyridin-4
      yl)-benzene sulphonamide (Ro 63-0563) had mean pKi values +/-s.e.mean at the rat
      5-HT6 receptor of 7.35+/-0.04 and 7.83+/-0.01, respectively and pKi values at the
      human 5-HT6 receptor of 7.26+/-0.06 and 7.91+/-0.02, respectively. 3 .Both
      compounds were found to be over 100 fold selective for the 5-HT6 receptor
      compared to 23 (Ro 04-6790) and 69 (Ro 63-0563) other receptor binding sites. 4.
      In functional studies, neither compound had any significant effect on basal
      levels of cyclicAMP accumulation in Hela cells stably expressing the human 5-HT6
      receptor, suggesting that the compounds are neither agonists nor inverse agonists
      at the 5-HT6 receptor. However, both Ro 04-6790 and Ro 63-0563 behaved as
      competitive antagonists with mean +/-s.e.mean pA2 values of 6.75+/-0.07 and
      7.10+/-0.09, respectively. 5. In rats habituated to observation cages, Ro 04-6790
      produced a behavioural syndrome similar to that seen following treatment with
      antisense oligonucleotides designed to reduce the expression of 5-HT6 receptors.
      This behavioural syndrome consisted of stretching, yawning and chewing. 6. Ro 04
      6790 and Ro 63-0563 represent valuable pharmacological tools for the
      identification of 5-HT6 receptors in natural tissues and the study of their
      physiological function.

PMID- 9647482
TI  - Effects of the cysteinyl leukotriene receptor antagonists pranlukast and
      zafirlukast on tracheal mucus secretion in ovalbumin-sensitized guinea-pigs in
      vitro.
AB  - 1. We investigated the inhibitory effects of the cysteinyl leukotriene (CysLT1)
      receptor antagonists, pranlukast and zafirlukast, on 35SO4 labelled mucus output,
      in vitro, in guinea-pig trachea, induced by leukotriene D4 (LTD4) or by antigen
      challenge of sensitized animals. Agonists and antagonists were administered
      mucosally, except in selected comparative experiments where drugs were
      administered both mucosally and serosally to assess the influence of the
      epithelium on evoked-secretion. 2. LTD4 increased 35SO4 output in a concentration
      related manner with a maximal increase of 23 fold above controls at 100 microM
      and an approximate EC50 of 2 microM. Combined mucosal and serosal addition of
      LTD4 did not significantly affect the secretory response compared with mucosal
      addition alone. Neither LTC4 nor LTE4 (10 microM each) affected 35SO4 output.
      Pranlukast or zafirlukast significantly inhibited 10 microM LTD4-evoked 35SO4
      output in a concentration-dependent fashion, with maximal inhibitions of 83% at
      10 microM pranlukast and 78% at 10 microM zafirlukast, and IC50 values of 0.3
      microM for pranlukast and 0.6 microM for zafirlukast. Combined mucosal and
      serosal administration of the antagonists (5 microM each) gave degrees of
      inhibition of mucosal-serosal 10 microM LTD4-evoked 35SO4 output similar to those
      of the drugs given mucosally. Pranlukast (0.5 microM) caused a parallel rightward
      shift of the LTD4 concentration-response curve with a pKB of 7. Pranlukast did
      not inhibit ATP-induced 35SO4 output. 3. Ovalbumin (10-500 microg ml(-1)
      challenge of tracheae from guinea-pigs actively sensitized with ovalbumin caused
      a concentration-related increase in 35SO4 output with a maximal increase of 20
      fold above vehicle controls at 200 microg ml(-1). The combination of the
      antihistamines pyrilamine and cimetidine (0.1 mM each) did not inhibit ovalbumin
      induced 35SO4 output in sensitized guinea-pigs. Neither mucosal (10 microM or 100
      microM) nor mucosal-serosal (100 microM) histamine had any significant effect on
      35SO4 output. 4. Pranlukast or zafirlukast (5 microM each) significantly
      suppressed ovalbumin-induced secretion in tracheae from sensitized guinea-pigs by
      70% and 65%, respectively. 5 We conclude that LTD4 or ovalbumin challenge of
      sensitized animals provokes mucus secretion from guinea-pig trachea in vitro and
      this effect is inhibited by the CysLT1 receptor antagonists pranlukast and
      zafirlukast. These antagonists may be beneficial in the treatment of allergic
      airway diseases in which mucus hypersecretion is a clinical symptom, for example
      asthma and allergic rhinitis.

PMID- 9647483
TI  - Effects of the 5-lipoxygenase activating protein inhibitor MK886 on voltage-gated
      and Ca2+-activated K+ currents in rat arterial myocytes.
AB  - 1. The effects on the voltage-gated (IK) and Ca2+ activated (I(K,Ca)) K+ currents
      in rat arterial myocytes of the 5-lipoxygenase activating protein (FLAP)
      inhibitor MK886, and its inactive analogue L583,916 were evaluated. 2. In rat
      pulmonary arterial myocytes (RPAMs), MK886 caused a concentration-dependent
      reduction of the IK, with little obvious change in the kinetics of the current.
      Half maximal current block was observed at 75 nM MK886. 3. MK886 application led
      to a concentration-dependent increase in the amplitude of the TEA-sensitive
      I(K,Ca) current and single channel activity in RPAMs in whole cell and inside-out
      configurations, respectively. The threshold concentration for this effect was
      approximately 300 nM and a maximal 4-5 fold increase was observed at 10 microM
      MK886. MK886 also increased I(K,Ca) in rat mesenteric arterial myocytes (RMAMs).
      4. L538,916, an analogue of MK886 which does not block FLAP, had no effect on
      either IK or I(K,Ca) at a concentration of 10 microM. 5. Leukotriene C4 (100 nM)
      had no effect on either IK or I(K,Ca) in RPAMs. MK886 produced its usual increase
      in I(K,Ca) and also blocked IK, in the presence of leukotriene C4. Similarly,
      leukotriene E4 (100 nM) did not alter the amplitude of IK. Also, the nonselective
      leukotriene receptor antagonist ICI 198,615 (3 microM) did not affect IK in
      RPAMs, and did not affect the response to MK886. 6. Arachidonic acid (10 microM)
      enhanced I(K,Ca) in both RPAMs and RMAMs. 7. The results show that MK886 markedly
      affects both IK and I(K,Ca) in a manner similar to that of arachidonic acid and
      independent of the endogenous production of leukotrienes. It is therefore
      possible that MK886, which is thought to compete with arachidonic acid for its
      binding to FLAP, may similarly occupy arachidonic acid binding sites on these K+
      channels, and mimic its effects. Alternatively, MK886 might act via non-selective
      effects on other arachidonic acid metabolites which could modify K+ channel
      function.

PMID- 9647484
TI  - T-type and L-type calcium channel blockers exert opposite effects on renin
      secretion and renin gene expression in conscious rats.
AB  - 1. This study aimed to investigate and to compare the effects of pharmacological
      T-type calcium channel and of L-type calcium channel blockade on the renin
      system. To this end, male healthy Sprague-Dawley rats were treated with the T
      channel blocker mibefradil or with the L-channel blocker amlodipine at doses of 5
      mg kg(-1), 15 mg kg(-1) and 45 mg kg(-1) per day for four days and their effects
      on plasma renin activity (PRA) and kidney renin mRNA levels were determined. 2.
      Whilst amlodipine lowered basal systolic blood pressure at 5 mg kg(-1),
      mibefradil had no effect on basal blood pressure in the whole dose range
      examined. Amlodipine dose-dependently induced up to 7 fold elevation of PRA and
      renin mRNA levels. Mibefradil significantly lowered PRA and renin mRNA levels at
      5 mg kg(-1) and moderately increased both parameters at a dose of 45 mg kg(-1),
      when PRA and renin mRNA levels were increased by 100% and 30%, respectively. In
      primary cultures of renal juxtaglomerular cells neither amlodipine nor mibefradil
      (0.1-10 microM) changed renin secretion. 3. In rats unilateral renal artery clips
      (2K-1C) mibefradil and amlodipine at doses of 15 mg kg(-1) day(-1) were equally
      effective in lowering blood pressure. In contrast mibefradil (5 mg kg(-1) and 15
      mg kg(-1) day(-1)) significantly attenuated the rise of PRA and renin mRNA
      levels, whilst amlodipine (15 mg kg(-1)) additionally elevated the rise of PRA
      and renin mRNA levels in response to renal artery clipping. 4. These findings
      suggest that T-type calcium channel blockers can inhibit renin secretion and
      renin gene expression in vivo, whilst L-type calcium channel blockers act as
      stimulators of the renin system. Since the inhibitory effect of T-type
      antagonists is apparent in vivo but not in vitro, one may infer that the effect
      on the renin system is indirect rather than directly mediated at the level of
      renal juxtaglomerular cells.

PMID- 9647485
TI  - Effects of inhibitors of the activity of cyclo-oxygenase-2 on the hypotension and
      multiple organ dysfunction caused by endotoxin: a comparison with dexamethasone.
AB  - 1. Endotoxaemia is associated with the expression of the inducible isoform of
      cyclo-oxygenase, cyclo-oxygenase-2 (COX-2), and an overproduction of arachidonic
      acid (AA) metabolites. The role of the AA metabolites generated by COX-2 in the
      circulatory failure and multiple organ dysfunction caused by endotoxin is
      unclear. Dexamethasone prevents the expression of COX-2 and exerts beneficial
      effects in animal models of shock. 2. Here we compare the effects of two
      inhibitors of COX-2 activity, namely NS-398 (5 mg kg(-1), i.p., n=7) and SC-58635
      (3 mg kg(-1), i.p., n=9) with those of dexamethasone (3 mg kg(-1), i.p., n=9) on
      the circulatory failure and organ dysfunction caused by lipopolysaccharide (LPS,
      E. coli, 6 mg kg(-1), i.v., n=11) in the rat. 3. Endotoxaemia for 6 h caused
      hypotension, acute renal dysfunction, hepatocellular injury, pancreatic injury
      and an increase in the plasma levels of 6-keto-PGF1alpha (indicator of the
      induction of COX-2) and nitrite/nitrate (indicator of the induction of iNOS). 4.
      Pretreatment of rats with dexamethasone attenuated the hypotension, the renal
      dysfunction, the hepatocellular and pancreatic injury and the induction of COX-2
      and iNOS caused by LPS. In contrast, inhibition of COX-2 activity with SC-58635
      or NS-398 neither attenuated the circulatory failure nor the multiple organ
      failure caused by endotoxin. 5. Thus, the prevention of the circulatory failure
      and the multiple organ injury/dysfunction caused by dexamethasone in the rat is
      not due to inhibition of the activity of COX-2. Our results suggest that an
      enhanced formation of eicosanoids by COX-2 does not contribute to the development
      of organ injury and/or dysfunction in rats with endotoxaemia.

PMID- 9647486
TI  - Species differences in the distribution of beta-adrenoceptor subtypes in bladder
      smooth muscle.
AB  - 1. The beta-adrenoceptor (beta-AR) subtypes mediating relaxation of the rabbit,
      rat and canine detrusors were subjected to functional investigation using
      selective beta-AR agonists and antagonists. 2. In all three species,
      isoprenaline, noradrenaline and adrenaline each produced a concentration
      dependent relaxation of the detrusor. The rank order for their relaxing potency
      was isoprenaline>adrenaline>noradrenaline in rabbits and rats, but
      isoprenaline>noradrenaline>adrenaline in dogs. 3. Dobutamine did not produce
      relaxation of the detrusors at concentrations that are selective for beta1-AR.
      The selective beta2-AR agonist, procaterol, had a more potent relaxing effect on
      rabbit and rat detrusors than on the canine detrusor. CGP-12177A, a selective
      beta3-AR agonist, was more effective in the rabbit than in the other two species.
      On the other hand, the relaxing effect of another beta3-AR agonist, CL316243, was
      more pronounced in dogs and rats than in rabbits. 4. CGP-20712A (10(-9) to 10(-7)
      M), a selective beta1-AR antagonist, caused a slight rightward shift of the
      concentration-relaxation response curve for isoprenaline in the canine detrusor
      (pA2 9.41), but not in the rabbit and rat detrusors. ICI-118,551, a selective
      beta2-AR antagonist, antagonized the isoprenaline-induced relaxation in rabbits
      (pA2 9.45) and rats (pA2 9.05), but not in dogs. Bupranolol, a non-selective beta
      AR antagonist, caused a rightward shift of the concentration-relaxation curve for
      isoprenaline in the rabbit (pA2 9.32) and rat (pA2 8.98). However, higher
      concentrations (3 x 10(-8) to 10(-5) M) were needed to induce a rightward shift
      of the curve for isoprenaline in the dog (pA2 8.19) than in the other two
      species. 5. We have confirmed that the distribution of beta-AR subtypes in the
      detrusor muscle varies significantly from species to species and we provide here
      the first evidence of the presence of beta3-AR in the detrusor. It is suggested
      that the relaxation induced by adrenoceptor agonists in urinary bladder smooth
      muscle may be mediated mainly via beta2-AR in rabbits, via both beta2- and beta3
      AR in rats, but mainly via beta3-AR in dogs.

PMID- 9647487
TI  - Effects of kappa-opioid receptor stimulation in the heart and the involvement of
      protein kinase C.
AB  - 1. The role of protein kinase C (PKC) in mediating the action of kappa-receptor
      stimulation on intracellular Ca2+ and cyclic AMP production was determined by
      studying the effects of trans-(+/-)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]
      cyclohexyl) benzeneacetamide methanesulphonate (U50,488H), a selective kappa
      receptor agonist, and phorbol 12-myristate 13-acetate (PMA), a PKC agonist, on
      the electrically-induced [Ca2+]i transient and forskolin-stimulated cyclic AMP
      accumulation in the presence and absence of a PKC antagonist, staurosporine or
      chelerythrine, in the single rat ventricular myocyte. 2. U50,488H at 2.5-40
      microM decreased both the electrically-induced [Ca2+]i transient and forskolin
      stimulated cyclic AMP accumulation dose-dependently, effects which PMA mimicked.
      The effects of the kappa-agonist, that were blocked by a selective kappa
      antagonist, nor-binaltorphimine, were significantly antagonized by the PKC
      antagonists, staurosporine and/or chelerythrine. The results indicate that PKC
      mediates the actions of kappa-receptor stimulation. 3. To determine whether the
      action of PKC was at the sarcoplasmic reticulum (SR) or not, the [Ca2+]i
      transient induced by caffeine, that depletes the SR of Ca2+, was used as an
      indicator of Ca2+ content in the SR. The caffeine-induced [Ca2+]i transient was
      significantly reduced by U50,488H at 20 microM. This effect of U50,488H on
      caffeine-induced [Ca2+]i transient was significantly attenuated by 1 microM
      chelerythrine, indicating that the action of PKC involves mobilization of Ca2+
      from the SR. When the increase in IP3 production in response to K-receptor
      stimulation with U50,488H in the ventricular myocyte was determined, the effect
      of U50,488H was the same in the presence and absence of staurosporine, suggesting
      that the effect of PKC activation subsequent to kappa-receptor stimulation does
      not involve IP3. The observations suggest that PKC may act directly at the SR. 4.
      In conclusion, the present study has provided evidence for the first time that
      PKC may be involved in the action of kappa-receptor stimulation on Ca2+ in the SR
      and cyclic AMP production, both of which play an essential role in Ca2+
      homeostasis in the heart.

PMID- 9647488
TI  - Selectivity of action of 8-alkylamino analogues of N6-cyclopentyladenosine in
      vivo: haemodynamic versus anti-lipolytic responses in rats.
AB  - 1. A1 adenosine receptor agonists with reduced intrinsic activity may be
      therapeutically useful as result of an increased selectivity of action. In this
      study the tissue selectivity of three 8-alkylamino substituted analogues of N6
      cyclopentyladenosine (CPA) was investigated for haemodynamic and anti-lipolytic
      effects using an integrated pharmacokinetic-pharmacodynamic approach. 2.
      Chronically instrumented male Wistar rats received intravenous infusions of 4.0
      mg kg(-1) 8-methylaminoCPA (8MCPA), 12.0 mg kg(-1) 8-ethylaminoCPA (8ECPA), 20.0
      mg kg(-1) 8-butylaminoCPA (8BCPA) or vehicle during 15 min. During
      experimentation, serial arterial blood samples were drawn for the determination
      of agonist concentrations and plasma non-esterified fatty acid (NEFA) levels.
      Blood pressure and heart rate were monitored continuously. In addition to the CPA
      analogues, each rat received a rapid bolus infusion of CPA to determine the
      maximal effects of the full agonist. 3. The concentration-time profiles of the
      CPA analogues could be described by a bi-exponential function. Values for
      clearance, volume of distribution at steady state and elimination half-life were
      44+/-5, 48+/-6 and 39+/-2 ml min(-1) kg(-1), 0.97+/-0.09, 0.84+/-0.10 and 1.05+/
      0.07 1 kg(-1) and 25+/-2, 28+/-2 and 40+/-2 min for 8MCPA, 8ECPA and 8BCPA,
      respectively (mean+/-s.e.mean, n=6-8). 4. Different models were used to derive
      the concentration-effect relationships for heart rate and NEFA, yielding
      estimates of potency (EC50) and intrinsic activity (Emax) for both effects of the
      compounds in vivo. On heart rate the compounds acted as partial agonists, with
      Emax values of -173+/-14, -131+/-11 and -71+/-6 beats min(-1) for 8MCPA, 8ECPA
      and 8BCPA, respectively. These Emax values were significantly lower than the
      maximal effect of CPA (-208+/-8 beats min(-1)). With regard to the anti-lipolytic
      effect all three compounds were full agonists and lowered NEFA levels to the same
      extent as CPA (69%). The estimated Emax values were 63+/-5, 63+/-4 and 68+/-2%,
      respectively. 5. Furthermore, the compounds were more potent in causing anti
      lipolytic than cardiovascular effects. The EC50 values for the NEFA and heart
      rate lowering effects were 37+/-15, 68+/-22 and 659+/-108 ng ml(-1) and 164+/-22,
      341+/-76 and 975+/-190 ng ml(-1) for 8MCPA, 8ECPA and 8BCPA, respectively (mean+/
      s.e.mean, n=6-8). 6. This study demonstrates that partial agonists for the A1
      adenosine receptor have increased selectivity of action in vivo. The 8-alkylamino
      analogues of CPA may be useful anti-lipolytics with less pronounced haemodynamic
      side effects.

PMID- 9647489
TI  - Carbamylated proteins and peptides in health and in uremia.

PMID- 9647490
TI  - Asymptomatic childhood hypertension.

PMID- 9647491
TI  - Secondary hyperparathyroidism in severe chronic renal failure is corrected by
      very-low dietary phosphate intake and calcium carbonate supplementation.
AB  - The main purpose of our study was to verify the effect of a very-low-protein, low
      phosphorus diet, supplemented with essential amino acids and keto analogues and
      with calcium carbonate, on circulating levels of intact parathyroid hormone (i
      PTH) in severe chronic renal failure patients with secondary hyperparathyroidism,
      not treated with any vitamin D preparation. To this aim, we shifted 21 chronic
      uremics (12 males, 9 females; age 56 +/- 13 years) with serum creatinine >6.5
      mg/dl and i-PTH >150 pg/ml, from a standard low-protein diet (0.6 g/kg/day
      approximately) to a very-low-protein (0.3 g/kg/day), very-low-phosphorus (5
      mg/kg/day) diet supplemented with a mixture of essential amino acids and calcium
      keto analogues (Ketodiet), calcium carbonate (2-4 g/day), iron, and vitamin B12
      preparations. The energy supply of both diets was 30-35 kcal/kg/day. Exclusion
      criteria were a poor compliance with dietary or supplement prescriptions or signs
      of autonomic hyperparathyroidism. After 4 +/- 2 months of Ketodiet, the i-PTH
      serum levels decreased by 49% as a mean (from 441 +/- 233 to 225 +/- 161 pg/ml, p
      < 0.001); serum phosphorus and alkaline phosphatase decreased, whereas serum
      calcium increased. The great reduction of serum and urinary urea demonstrated a
      good compliance with Ketodiet, and no sign of protein malnutrition was observed.
      These findings confirm that even in severe chronic uremic patients dietary
      phosphorus restriction and calcium carbonate supplementation lower i-PTH serum
      levels. This is one of the goals of the dietary treatment that can be safely
      achieved, provided good compliance both with the dietary prescriptions and with
      adequate energy and supplement intakes.

PMID- 9647492
TI  - End-stage renal disease following polycythemia vera: in vitro and in vivo
      response of erythroid progenitors to erythropoietin and effects of sera on normal
      erythropoiesis.
AB  - We investigated the in vitro erythroid progenitor growth and the effects of sera
      on normal-marrow CFU-E (colony-forming units - erythroid) growth in 2 patients
      with renal failure on regular hemodialysis following a prior history of
      polycythemia vera (PV). PV was diagnosed 3 and 11 years, respectively, before the
      development of terminal renal failure. One of the patients had entered a spent
      phase of PV as characterized by diffuse extensive myelofibrosis and anemia; the
      other also had mild myelofibrosis. The serum erythropoietin (EPO) levels were low
      or normal on serial measurements by radioimmunoassay. There was no correlation
      between the hematocrit values and serum EPO levels. EPO-independent erythroid
      colonies were present in the cultures of bone marrow and peripheral blood cells
      from both patients after renal failure in the anemic state. With the addition of
      various concentrations of EPO, the number of erythroid colonies increased as the
      concentrations of EPO increased which was in accordance with the clinical
      observation that 1 patient with postpolycythemic myeloid metaplasia partially
      responded to recombinant human EPO therapy. In the EPO-dependent CFU-E assay,
      normal-marrow CFU-E numbers supported by 10% of the patient sera were less than
      those by normal sera. In the absence of EPO in cultures, no erythropoietic
      activity was found in the patients' sera. Our study on uremic patients with
      underlying PV showed that the biologic characteristics of autonomous erythroid
      progenitor growth for PV persisted during the spent phase and after the
      development of terminal renal failure with anemia. The erythroid progenitors
      responded to EPO both in vitro and in vivo. Their sera exhibited an inhibiting
      effect on the growth of normal-marrow erythroid progenitors.

PMID- 9647493
TI  - Long-term enalapril therapy in patients with chronic renal failure on a low
      protein diet. A prospective randomized comparison with metoprolol.
AB  - The effect of enalapril (5-10 mg/day) on the progression of chronic renal failure
      (CRF) was compared with that of metoprolol (40-120 mg/day) in 28 patients for 24
      months in a prospective study. Throughout the study, there was no significant
      difference between the 2 groups in protein intake and urinary sodium excretion.
      But there was a significant difference between the 2 groups in diastolic and mean
      arterial blood pressure at 6 months. In the serum creatinine level, there was a
      significant difference between the 2 groups at 6, 12, 18, and 24 months. In
      creatinine clearance, there was a significant difference between the 2 groups at
      24 months. In addition, the progression of CRF was significantly faster in the
      metoprolol group than the enalapril group as estimated from the slope of
      creatinine clearance (p < 0.05) and the slope of glomerular filtration rate (p <
      0.0005). In urinary protein excretion, there was a significant difference between
      the 2 groups at 6 and 18 months (p < 0.05). These findings indicate that
      enalapril has a suppressive effect on the progression of CRF and also has an
      antiproteinuric effect by a mechanism independent of its antihypertensive effect.

PMID- 9647494
TI  - Direct method for the measurement of low-density lipoprotein cholesterol levels
      in patients with chronic renal disease: a comparative assessment.
AB  - BACKGROUND/AIM: This study was performed to comparatively evaluate the results
      obtained for low-density lipoprotein (LDL) cholesterol concentrations by either a
      newly described direct method or the Friedewald equation in subjects with and
      without chronic renal disease. METHODS: Fasting plasma was obtained from a total
      of 169 subjects, 105 with normal renal function (including 53 hyperlipidaemic)
      and 64 with chronic renal disease (nephrotic syndrome and/or chronic renal
      failure; including 40 hyperlipidaemic patients), and analyzed for LDL cholesterol
      using the Friedewald equation and a direct LDL assay method. RESULTS: The
      Friedewald equation and the direct LDL cholesterol assay correlated well with
      each other (r = 0.79-0.90 in all subjects with plasma triglyceride, TG, levels
      greater than or less than 4.0 mmol/l and with and without chronic renal disease
      and/or hyperlipidaemia, all p < 0.0001). The values for LDL cholesterol, however,
      tended to be higher with the direct measurement. This mean difference was trivial
      in hyperlipidaemic subjects with (8.5%) and without (7.1%) normal renal function
      (both p < 0.05), but could be clinically significant in those with TG >4.0 mmol/l
      (mean difference 18%, p < 0.001). Indeed, bias plots confirmed this observation
      of wider negative bias for Friedewald estimation in these moderately
      hypertriglyceridaemic subjects. CONCLUSION: For most routine laboratories the
      options immediately available for assessment of lipid levels are the Friedewald
      equation or the direct measurement. The Friedewald equation and the direct assay
      method for LDL cholesterol are about equally good for assessment of the LDL
      status in patients with chronic renal disease and plasma TG <4.0 mmol/l. Where
      there are restraints on laboratory budgets, it would appear appropriate that the
      more expensive direct assay method be restricted to cases in whom plasma TG >4.0
      mmol/l or to patients who, for whatever reason, are unable to produce fasting
      samples.

PMID- 9647495
TI  - Effects of extracorporeal shock wave lithotripsy on renal function in patients
      with kidney stone disease.
AB  - The effects of extracorporeal shock wave lithotripsy on glomerular and tubular
      renal functions were determined by serum beta2-microglobulin (Sbeta2m) and
      urinary beta2-microglobulin (Ubeta2m) estimations in patients with
      nephrolithiasis. Unilateral treatment was performed in all patients. Urinary and
      serum creatinine levels were determined according to the method of Yatzidis.
      Sbeta2m and Ubeta2m were measured by radioimmunoassay the day before ESWL, on the
      day of ESWL, and then 1, 2, 5, 7, 8, 9, 14, and 28 days after treatment.
      Creatinine clearance, hourly urinary beta2m excretion (Ubeta2m/h), and tubular
      reabsorption of beta2m (TRbeta2m) were calculated. After lithotripsy, significant
      increases in Ubeta2m, Ubeta2m/h, and TRbeta2m were found (p < 0.001), whereas
      Sbeta2m, serum creatinine, and creatinine clearance values remained unchanged.
      Ubeta2m, Ubeta2m/h, and TRbeta2m reached their pretreatment values within 7-9
      days after ESWL. We concluded that ESWL does not affect the glomerular filtration
      rate; however, it leads to a transient proximal tubular dysfunction.

PMID- 9647496
TI  - Urinary excretion of Tamm-Horsfall protein and epidermal growth factor in chronic
      nephropathy.
AB  - Tamm-Horsfall protein (THP) and epidermal growth factor (EGF) are both
      synthesized by tubular cells in the distal part of the nephron and excreted with
      the urine. The present study examines the urinary excretion rates of the two
      peptides in relation to functional tubular markers in patients with chronic
      nephropathy. Four groups of patients with moderate to severely reduced renal
      function were studied: glomerulonephritis (n = 10), diabetic nephropathy (n =
      11), tubulointerstitial nephropathy (n = 13), and polycystic kidney disease (n =
      8). The renal function was evaluated by glomerular filtration rate (GFR) as an
      indicator for the general renal function, lithium clearance (C(Li)) as an
      indicator for proximal tubular function, and absolute distal reabsorption of
      sodium (ADR(Na)) as an indicator for distal tubular function. The excretion rate
      of EGF was rather closely correlated with GFR, C(Li) and ADR(Na) (Spearman
      coefficients of variation 0.88, 0.69, and 0.74, respectively). The correlations
      between the excretion rate of THP and GFR, C(Li) and ADR(Na) were weaker
      (Spearman coefficients of variation 0.68, 0.42, and 0.44). When the effect of GFR
      had been accounted for by multiple variance analyses, the excretion rates of the
      two peptides were still associated with ADR(Na) but not with C(Li). In
      conclusion, the urinary excretion rates of especially EGF but also those of THP
      were correlated with renal function and distal tubular reabsorption of sodium in
      patients with chronic nephropathy.

PMID- 9647497
TI  - Comparison of a vegetable-based (soya) and an animal-based low-protein diet in
      predialysis chronic renal failure patients.
AB  - There is some experimental evidence to suggest that progression of chronic renal
      failure (CRF) is slower on diets based on soya protein than on diets based on
      animal protein. We have compared the effect of a soya-based vegetarian low
      protein diet (VPD) and an animal-based low-protein diet (APD) in 15 patients with
      CRF. 15 patients with CRF (51Cr-EDTA-measured glomerular filtration rate 15-50
      ml/min/1.73 m2) were studied. In a randomized crossover trial, the patients were
      given each diet (each containing 0.75 g protein and 32 kcal per kilogram body
      weight) for a 6-month period. Nine patients completed the trial, 2 others dropped
      out because they could not tolerate the VPD, 3 because of unrelated medical
      complications, and 1 for technical reasons. The caloric intake was higher and the
      protein, phosphate and essential amino acid intake lower on the VPD than on the
      APD. The compliance with the suggested caloric intake was better with the VPD
      than with the APD (97 vs. 88% of recommended intake), as was the compliance with
      the suggested protein intake (94 vs. 112% of recommended intake) and with the
      suggested phosphate intake (102 vs. 116%). The mean glomerular filtration rate,
      as judged by 51Cr-EDTA, was similar after 6 months on each diet and remained
      unchanged throughout the entire year of the study. The rate of fall of glomerular
      filtration, as measured by the slope of 1/serum creatinine was slowed by 73%
      during the 1-year study period as compared with the prestudy period. Nutritional
      status (as measured by body mass index, midarm circumference, and lean body mass
      and percent body fat), serum transferrin, cholesterol and albumin, and total
      lymphocyte count were similar on the two diets. The serum albumin level on both
      diets, however, was significantly higher on the two diets than during the prediet
      period. Blood urea nitrogen, urine urea nitrogen, protein catabolic rate, and 24
      hour urine creatinine and phosphate were lower on the VPD than on the APD. The 24
      hour protein excretion was similar on the two diets. The two low-protein diets
      resulted in a slowing in the progression of CRF. A VPD is well tolerated in CRF
      and is associated with lower protein and phosphate intakes and a higher caloric
      intake than an APD and may, therefore, be used as a safe alternative or partial
      substitute for the usual APD in CRF.

PMID- 9647498
TI  - Antioxidant defense potential of rabbit renal tissues after ESWL: protective
      effects of antioxidant vitamins.
AB  - Antioxidant defense potential, malondialdehyde (MDA) levels, and relative
      hydroxyl radical (OH.) concentrations were measured in order to establish the
      effects of extracorporeal shock wave lithotripsy (ESWL) on free radical
      production and antioxidant defense potential of the rabbit kidney tissues.
      Electron microscopic examination was also performed to observe ultrastructural
      changes. The antioxidant defense potential of the ESWL-treated tissues was found
      to be reduced, and the MDA levels increased as compared with controls. Vitamin
      (vitamin E plus C combination) pretreatment ameliorated antioxidant defense
      potential in part, prevented increases in MDA levels in the ESWL-treated tissues,
      and increased the antioxidant defense potential in the control kidney tissues.
      After ESWL, a significant amount of OH. radical was measured in the affected
      tissue. This revealed the source of oxidant stress and peroxidation reactions in
      the ESWL-treated kidney tissue. Vitamin pretreatment caused significant reduction
      in the OH. radical concentration. In the electron microscopic investigation, some
      significant subcellular changes, such as endothelial injury, loss of foot
      processes, damage of glomerular basal membrane, etc., were observed in the ESWL
      treated renal tissue slices. Vitamin pretreatment to a great extent prevented
      formation of these subcellular changes. Our results suggest that the antioxidant
      capacity of the kidney tissue was reduced after ESWL treatment and that the
      tissue was exposed to oxidant stress. Vitamin pretreatment exerted significant
      protection against the radical damage.

PMID- 9647499
TI  - Apoptosis and expression of Bax protein and Fas antigen in glomeruli of a remnant
      kidney model.
AB  - The role of apoptosis in glomerular cell depletion associated with a decrease in
      renal function is still controversial. To examine the involvement of apoptosis in
      renal disease, the occurrence of apoptosis during the progression of renal
      insufficiency as well as the expression of Bax protein and Fas antigen that are
      related to the apoptosis were investigated using five-sixths nephrectomized rats,
      one of the progressive renal disease models. Serum creatinine was significantly
      elevated to a level approximately five-fold higher than that in the sham-operated
      group on day 1 after the five-sixths nephrectomy and then maintained at a level
      approximately two- to three-fold higher until day 56 and then elevated further to
      a level eight-fold higher on day 96 after nephrectomy as compared with the sham
      operated group. The total number of glomerular cells was significantly increased
      from day 7 to day 56 after nephrectomy and then returned to the level of the sham
      operated group by day 96. The number of PCNA-positive cells (a marker of
      proliferating cells) in the glomeruli was significantly increased from day 7 to
      day 28 after nephrectomy; the highest level was observed on day 7, and the
      numbers then decreased gradually. Apoptotic cells, which were represented by
      TUNEL-positive cells, as well as apoptotic bodies were persistently increased
      with time after nephrectomy in the glomeruli of nephrectomized rats; apoptotic
      cells could hardly be observed in the sham-operated group. Therefore, glomerular
      cell proliferation appeared to begin immediately after nephrectomy and to
      continue until day 28 at a level high enough to overcome the decrease in the
      number of glomerular cells due to apoptosis, since the total number of glomerular
      cells was apparently high until day 56. On day 96, the decrease in the number of
      glomerular cells probably becomes predominant over cell proliferation, since
      apoptosis continuously increased with time after nephrectomy. The events on day
      96 may be associated with the severely decreased renal function which was
      represented by the explosive increase in the serum creatinine level on the same
      day. The number of Fas antigen positive glomerular cells was increased from day 1
      after nephrectomy and reached a plateau on day 21. The number of Bax protein
      positive glomerular cells was generally increased with time after nephrectomy,
      but the number was slightly decreased on day 21. The theory that the expression
      of Bax protein is correlated with apoptosis appears to fit the case of
      progressive renal disease. These results suggest that apoptosis is involved in
      the cell depletion of progressive renal insufficiency.

PMID- 9647500
TI  - Acute volume expansion and salt-loading studies in rats. The role of atrial
      natriuretic peptide and catecholamines.
AB  - Differences have been postulated for the mechanism of natriuresis due to atrial
      natriuretic peptide (ANP), salt loading with high salt diet (HS) and acute volume
      expansion (AcVE), in particular between AcVE and ANP based on the observed
      synergism between the two. Therefore the effects of and the interaction between
      the three were investigated in rats. ANP and AcVE produced the same natriuresis
      in HS as in normal salt (NS) rats and, in both, the actions of ANP and AcVe were
      significantly additive showing similarity in mechanisms. Synergism [(AcVE + ANP) 
      AcVE] was, however, present only in the NS rats. Proximal tubular sodium
      transport was the same with AcVE and ANP+AcVE suggesting that synergism is a
      property of more distal nephron segments. In conscious HS rats, plasma ANP was
      significantly less but natriuresis was higher than in NS rats. ANP therefore
      probably has some causative role in the natriuresis of AcVE but none in that of
      HS loading. Urinary dopamine was significantly increased by HS and further
      increased by AcVE in both NS and HS rats, the relationship between dopamine and
      natriuresis being significantly positive (r2 = 0.328) reaching equivalent levels
      in both NS and HS rats. Systemic benserazide prevented the increase in urinary
      dopamine but only attenuated the natriuresis of AcVE. We conclude that HS does
      not potentiate the natriuresis of AcVE or ANP, synergism between AcVE and ANP is
      not a proximal tubule event and dopamine accounts for significant natriuresis of
      VE in addition to other natriuretic factors.

PMID- 9647501
TI  - High-protein diet or unilateral nephrectomy induces a humoral factor(s) that
      enhances mesangial cell proliferation in culture.
AB  - BACKGROUND: A high-protein diet is one of the maneuvers which produce hypertrophy
      of kidney mass. The underlying mechanism(s) has not been elucidated. In the
      present study, we investigated the possibility that a humoral factor may be
      involved. METHODS: Twenty-eight 3-week-old Charles River rats were studied.
      Fourteen underwent right nephrectomy and 14 sham operation. Each of these groups
      was divided into two equal subgroups (n = 7 in each): one maintained on a regular
      diet (20% protein) and the other on a high-protein diet (60% protein) for 7 days.
      Following this period the animals were sacrificed. Sera from the animals were
      added to mesangial cell cultures from kidneys of intact 3-week-old rats, and the
      thymidine incorporation was assessed. RESULTS: The parameters of kidney mass
      indicated that the high-protein diet indeed produced kidney hypertrophy. Sera
      from the sham-nephrectomized animals fed a high-protein diet produced a
      significantly greater proliferative effect on mesangial cells in culture than
      sera from the respective animals on a normal-protein diet. Sera from either
      nephrectomized group or from the high-protein sham-operated group all had similar
      magnitudes of enhancement of mesangial cell proliferation. CONCLUSION: We
      conclude that the renal hypertrophy produced by a high-protein diet is mediated,
      at least in part, by a humoral factor(s).

PMID- 9647502
TI  - Recovery of damaged glomerular capillary network with endothelial cell apoptosis
      in experimental proliferative glomerulonephritis.
AB  - Capillary repair can occur in damaged glomeruli in recovery models of
      glomerulonephritis (GN). In order to clarify whether capillary repair is an
      essential component in glomerular recovery from GN, we have examined the
      development of the capillary repair after inflammatory injury in both the
      repairing glomeruli and the segmental sclerotic scar lesions in Thy-1 GN.
      Mesangiolytic glomerular damage was induced in rats with anti-Thy-1.1 antibody
      administration. Diffuse mesangiolysis and segmental microaneurysmal ballooning
      developed in damaged glomeruli by day 3, with reduction of endothelial
      cellularity. Thereafter, histological proliferative GN developed between day 5
      and week 3. Endothelial cell proliferation began on day 1 and peaked on day 5,
      and the number of glomerular endothelial cells increased and exceeded the level
      of control values on day 7. Angiogenic glomerular capillary repair occurred
      through the process of not only capillary regeneration from remaining endothelial
      cells in capillary aneurysmal lesions but also new capillary growth derived from
      the glomerular vascular poles by day 7. The number of glomerular capillary lumina
      also increased to the level of controls by week 3. Subsequently, mesangial
      proliferative GN resolved, and most of the glomeruli recovered to their normal
      structure with the reconstruction of the capillary network by weeks 4-6. In the
      glomerular capillary repair, significant apoptosis of glomerular endothelial
      cells was present during the period of mild endothelial cell hypercellularity
      between day 7 and day 10 (0.06 +/- 0.02 apoptotic endothelial cells/glomerular
      cross section vs. 0.00 +/- 0.00 in controls, mean +/- SEM; p < 0.05. In Thy-1 GN,
      most of the damaged glomeruli recovered with angiogenic capillary repair.
      However, segmental sclerotic scar lesions remained in 10-30% of the glomeruli
      with an incomplete repair of glomerular capillaries. Therefore, it is concluded
      that following the destruction of the glomerular capillary network in GN,
      angiogenic capillary repair plays an essential role in the recovery of damaged
      glomeruli, and incomplete capillary repair leads to sclerotic scar lesions in
      damaged glomeruli. Glomerular capillary repair occurs through the process of
      capillary regeneration from remaining endothelial cells as well as new glomerular
      capillary growth from the glomerular vascular poles. In glomerular capillary
      repair, apoptosis is necessary in regulating the number of intrinsic endothelial
      cells.

PMID- 9647503
TI  - Primary hyperparathyroidism in a patient with systemic lupus erythematosus
      antiphospholipid syndrome.

PMID- 9647504
TI  - In vitro production of interleukin-1, interleukin-6 and tumor necrosis factor
      alpha by different blood cells in patients on intermittent peritoneal dialysis.

PMID- 9647505
TI  - A case of amyloidal anal polyp in long-term hemodialysis.

PMID- 9647506
TI  - IgA nephropathy: to treat or not to treat?

PMID- 9647507
TI  - High prevalence of hepatitis C virus infection in one dialysis center in
      Bulgaria.

PMID- 9647508
TI  - Exercise training and the progression of chronic renal failure.

PMID- 9647509
TI  - Anti-glomerular basement membrane and anti-neutrophil cytoplasm antibody-positive
      vasculitis presenting with peripheral neuropathy and acute renal failure.

PMID- 9647510
TI  - Gabexate mesilate plus intravenous gammaglobulin treatment in children with
      diarrhoea-associated haemolytic uraemic syndrome.

PMID- 9647511
TI  - Treatment of chronic hepatitis C with interferon alpha in patients on maintenance
      hemodialysis.

PMID- 9647512
TI  - Renal functional reserve in asymptomatic carriers of human immunodeficiency
      virus.

PMID- 9647513
TI  - Fluorosis, osteomalacia and pseudohyperparathyroidism in a patient with renal
      failure.

PMID- 9647514
TI  - Nephrotic syndrome associated with inflammatory bowel disease treated by
      mesalazine.

PMID- 9647515
TI  - Alport syndrome in Reunion Island: phenotypic heterogeneity of the recessive
      autosomal form.

PMID- 9647516
TI  - Rapidly progressive immunotactoid glomerulonephritis and multiple myeloma.

PMID- 9647517
TI  - Mediterranean spotted fever with acute renal failure stimulating a relapse in C
      ANCA vasculitis.

PMID- 9647519
TI  - Association of Gitelman's syndrome and focal glomerulosclerosis.

PMID- 9647518
TI  - Is the hepatitis C seroconversion rate higher with dialysis catheters than A-V
      fistula.

PMID- 9647520
TI  - Prevalence of heparin-induced PF4-heparin antibodies in hemodialysis patients.

PMID- 9647521
TI  - Normotensive primary aldosteronism due to adrenocortical carcinoma.

PMID- 9647522
TI  - Learning from the past, venous thromboembolism and the pill: an endless saga.

PMID- 9647523
TI  - Recommendations on the safety of oral contraceptives are too important for the
      regulating agencies alone.

PMID- 9647524
TI  - Thromboembolism and the pill: the saga must end.

PMID- 9647525
TI  - Incomplete compensation following the ban on third generation oral
      contraceptives.

PMID- 9647526
TI  - The pill and venous thromboembolism: a disarray of several layers of debate.

PMID- 9647527
TI  - Learning from the past: an essential need.

PMID- 9647528
TI  - Friendly IVF: the way of the future?

PMID- 9647529
TI  - Prenatal testing for late-onset diseases such as mutations in the breast cancer
      gene 1 (BRCA1). Just a choice or a step in the wrong direction?

PMID- 9647530
TI  - A rational approach to prenatal screening and intervention.

PMID- 9647531
TI  - The donation of gametes is possible without paying donors: experience of the
      French CECOS Federation. Centre for the cryopreservation of eggs and semen.

PMID- 9647532
TI  - Recruitment of gamete donors and payment of expenses.

PMID- 9647533
TI  - Development of human primordial follicles to antral stages in SCID/hpg mice
      stimulated with follicle stimulating hormone.
AB  - In contrast to the many detailed studies of Graafian follicles, the biology of
      small follicles in the human ovary is poorly understood and the trigger for
      follicular growth initiation remains unknown. No practical model exists to study
      preantral follicle growth in the human because of their slow growth rate and lack
      of an effective culture system. We therefore tested ovarian xenografts as a new
      strategy to study the early stages of ovarian follicular growth in vivo. Mice
      homozygous for severe combined immunodeficiency (SCID) and hypogonadism (hpg)
      received human ovarian xenografts under their kidney capsules. Follicle growth
      was assessed by morphology and proliferating cell nuclear antigen (PCNA)
      immunostaining. The grafts were recovered after 11 (short-term) and 17 weeks
      (long-term), and serially sectioned. During the last 6 weeks of long-term
      grafting, mice were randomized to receive either placebo or 1 IU of purified
      follicle stimulating hormone (FSH) s.c. on alternating days. After 11 weeks of
      grafting, the most advanced follicles had a maximum of two granulosa cell layers.
      In the absence of FSH administration, follicles did not progress beyond the two
      layer stage even after 17 weeks of grafting, and the oestradiol levels remained
      undetectable. In the FSH-treated long-term grafts, follicles had grown to antral
      stages and resulted in oestradiol levels as high as 2070 pmol/l. Growth
      initiation indices did not differ between control and FSH-treated grafts. This
      study demonstrates that follicles can survive and grow in human ovarian tissue
      grafted under the renal capsules of immunodeficient mice for at least 17 weeks,
      and indicate that xenograft models are potentially useful for studying human
      follicle development. Using this physiological model, we showed that FSH is
      required for follicle growth beyond the two-layer stage, although growth
      initiation is independent of gonadotrophin stimulation.

PMID- 9647534
TI  - The effect of recombinant follicle stimulating hormone (Gonal-F) on endogenous
      luteinizing hormone secretion in women.
AB  - Parenteral administration of follicle stimulating hormone (FSH) has been shown to
      lower luteinizing hormone (LH) concentrations in women undergoing ovulation
      induction. This study was designed to explore the physiological mechanism of this
      effect. Seven healthy women were recruited into a double-blind placebo-controlled
      study. LH secretion, after the administration of variable i.v. boluses (37.5, 75
      and 150 IU) of recombinant FSH (Gonal-F), was evaluated. LH was measured at 10
      min intervals for 2 h before and 4 h after the FSH/placebo infusion. LH pulse
      frequency and amplitude were evaluated and there was no significant difference
      between control and trial cycles for each subject. A linear regression analysis
      revealed that in the group receiving 150 IU FSH, the mean plasma LH concentration
      decreased significantly due to a reduction tonic LH secretion. This could be a
      result of the suppression of secretion or an alteration of clearance. This
      decrease was not seen in the other dosage groups, revealing that above a dosage
      threshold, FSH reduced non-pulsatile LH secretion. Therefore the effect of FSH in
      this study exposed the likely presence of two components of LH concentration: an
      FSH-sensitive, non-pulsatile tonic secretion and a gonadotrophin-releasing
      hormone-stimulated, pulsatile release that is unaffected by FSH. Although an
      indirect effect involving ovarian regulation is not excluded, the rapidity of the
      effect suggests that FSH acts directly on the pituitary gland.

PMID- 9647535
TI  - Human follicle fluid vascular endothelial growth factor concentrations are
      correlated with luteinization in spontaneously developing follicles.
AB  - Vascular endothelial growth factor (VEGF) is a cytokine that induces
      angiogenesis. Angiogenesis is a prominent histologic component of the
      luteinization process. Luteinization is also characterized by granulosa cell
      progesterone secretion in response to the luteinizing hormone (LH) surge. Local
      VEGF production in human pre-ovulatory follicles, induced by LH, was postulated
      to be a luteinization mediator in women. To investigate this hypothesis, serum
      and fluid from the dominant follicle of 31 healthy regularly cycling multiparous
      women undergoing laparoscopic sterilization were obtained. VEGF was measured by
      enzyme-linked immunosorbent assay, and LH and progesterone were measured by
      radioimmunoassay. Follicle aspiration was performed at a median of 13 days from
      the last menstrual period (range 11-17 days). The median pre-ovulatory follicle
      diameter was 16 mm (range 11-23 mm). Follicle fluid VEGF concentrations (mean
      6900 pg/ml, range 1200-17 100 pg/ml) were correlated positively with follicle
      fluid progesterone concentrations (mean 10 176 nmol/l, range 636-66780 nmol/l,
      r=0.62, P=0.002). This correlation was even tighter (r=0.87, P < 0.0001) when
      only samples from the 22 women in the earliest stages of follicle luteinization
      were considered. In these women serum LH concentrations were also correlated with
      follicle fluid VEGF concentrations (r=0.51, P=0.02). Our findings demonstrate the
      close dynamic relationship between VEGF production and early luteinization in
      human follicles during normal non-stimulated cycles.

PMID- 9647536
TI  - The use of long- and short-acting forms of gonadotrophin-releasing hormone
      analogues in women undergoing oocyte donation.
AB  - Evidence accumulated in in-vitro fertilization (IVF) cycles suggests that the use
      of long-acting forms of gonadotrophin-releasing hormone analogues (GnRHa) for
      pituitary desensitization may impair the outcome of IVF as compared to classical
      short-acting formulations. Whether the negative effects are directed against the
      corpus luteum, the endometrium, or both is unknown. However, the presence of high
      affinity binding sites for gonadotrophin-releasing hormone (GnRH) in the human
      endometrium suggests a possible role of these analogues on this target organ,
      affecting embryo implantation. In the present study, we tested direct effects of
      two different forms of GnRHa on implantation using the ovum donation model.
      Patients were prospectively allocated to one of the three study groups: the short
      acting form of the analogue leuprolide acetate (group I; n=64), the long-acting
      form of the same analogue (group II; n=58), and the long-acting preparation of
      the analogue tryptorelin (group III; n=61). A total of 68 cycles of embryo
      transfer was carried out in group I, whereas 67 were performed in group II and 65
      in group III. Cancellation rates were respectively 18.1, 17.3 and 18.8% because
      of bleeding while being on the waiting list for anonymous oocyte donation. The
      number of oocytes donated, fertilization rates and embryos replaced in each group
      were similar. As a result, pregnancy rate per transfer was 38.2, 49.3 and 44.6%
      respectively. Implantation rates per embryo replaced were respectively 13.4, 19.1
      and 17.0%. These data suggest that the use of a long-acting form of GnRHa
      provides success rates similar to the short-acting preparations, resulting in
      more convenient medication for patients with ovarian function included in ovum
      donation programmes.

PMID- 9647537
TI  - Leptin concentrations in the follicular phase of spontaneous cycles and cycles
      superovulated with follicle stimulating hormone.
AB  - It has been reported that oestradiol may play a role in the production of leptin
      from adipocytes. To investigate this relationship further, nine normally
      ovulating women were studied during two menstrual cycles, i.e. an untreated
      spontaneous cycle and a cycle treated with follicle stimulating hormone (FSH)
      from cycle day 2 until the day of human chorionic gonadotrophin (HCG) injection.
      Serum leptin values on cycle day 2 did not differ significantly between the
      spontaneous and the FSH cycles. In the spontaneous cycles, leptin values declined
      gradually and significantly up to day 7 and then increased progressively up to
      the day of luteinizing hormone (LH) surge onset, at which point they achieved the
      highest values. In the FSH cycles, serum leptin values increased gradually and
      significantly up to day 6, remaining stable thereafter, and were in the
      midfollicular phase significantly higher than in the spontaneous cycles.
      Significant positive correlations were found between mean values of leptin and
      mean values of oestradiol during the second half of the follicular phase in the
      spontaneous cycles and during the first half in the FSH cycles. A significant
      negative correlation was found between these two parameters in the spontaneous
      cycles during the first half of the follicular phase. Serum leptin levels were
      significantly higher in the midluteal than in the follicular phase in both
      cycles. These results demonstrate for the first time significant changes in
      leptin values during the follicular phase of the human menstrual cycle and a
      significant increase during superovulation induction with FSH. It is suggested
      that oestradiol may be involved in the regulation of leptin production in women.

PMID- 9647538
TI  - Does withholding gonadotrophin administration prevent severe ovarian
      hyperstimulation syndrome?
AB  - Withholding gonadotrophin administration (coasting) may prevent severe ovarian
      hyperstimulation syndrome (OHSS). To ascertain the effectiveness of this
      protection a cohort of 252 consecutive in-vitro fertilization (IVF) or IVF with
      intracytoplasmic sperm injection (ICSI) cycles was studied. Twenty women with
      exaggerated response were treated with coasting. Despite coasting, four patients
      developed severe OHSS requiring hospitalization. Two of these four patients also
      required paracentesis. Multiple regression analysis in coasting cycles revealed
      severe OHSS was related to youth, number of oocytes retrieved and serum
      oestradiol prior to human chorionic gonadotrophin (HCG). Risk of developing
      severe OHSS was multifactorial and not necessarily prevented by withholding
      gonadotrophin.

PMID- 9647539
TI  - Effect of delta-opioid receptor agonist deltorphin on circulating concentrations
      of luteinizing hormone and follicle stimulating hormone in healthy fertile women.
AB  - There is evidence that endogenous opioid peptides exert an inhibitory effect on
      pituitary luteinizing hormone (LH) secretion both in animals and in humans, by
      interacting with mu-opioid receptors. However, a role for delta-opioid receptors
      in the regulation of gonadotrophin releasing hormone (GnRH) secretion has
      recently been suggested. In the present study, we evaluated the effect of the
      highly selective delta-opioid receptor agonist deltorphin on the LH and follicle
      stimulating hormone (FSH) responses to naloxone in six healthy fertile women
      during the luteal phase of the menstrual cycle. Deltorphin infusion alone (7
      microg/kg/min for 60 min) did not significantly change the basal serum
      concentrations of LH in this group of women. The intravenous (i.v.) bolus
      administration of naloxone (15 mg) induced a significant (P < 0.001) increase in
      serum LH concentrations (from a mean basal value of 4.24+/-1.10 IU/l to a peak of
      13.27+/-1.8 IU/l). The LH response to naloxone was significantly (P < 0.001)
      blunted by preinfusion of deltorphin (13.27+/- 1.80 IU/l versus 4.80+/-1.18
      IU/l). No significant changes in FSH concentrations were observed during
      deltorphin, naloxone or deltorphin plus naloxone administration. These data
      indicate that activation of delta-opioid receptors can reduce naloxone-induced LH
      release, suggesting a possible role of delta receptors in opioidergic modulation
      of LH secretion in women.

PMID- 9647540
TI  - Endocytosis and MHC class II expression by human oviductal epithelium according
      to stage of the menstrual cycle.
AB  - The epithelium is the first barrier against pathogens invading the lumen of the
      human oviduct. Its expression of class II major histocompatibility complex (MHC
      class II) proteins suggests that it might play a role in antigen presentation
      during the local immune response. To study the role of the oviductal epithelium
      in antigen processing, its endocytic properties and MHC class II expression were
      examined. For assay of endocytosis, fluorescein isothiocyanate-labelled bovine
      serum albumin (BSA-FITC) or Escherichia coli (E. coli-FITC) was infused into the
      lumen. One-centimetre pieces of oviduct were incubated for 2 h and processed for
      fluorescence and confocal microscopy, and transmission electron microscopy.
      Incorporation into secretory and ciliated epithelial cells was observed, which
      was unrelated to the phase of the menstrual cycle. Small pieces of the organs
      were frozen and processed for immunohistochemistry. Most oviducts expressed MHC
      class II (HLA.DR) in the epithelium and in some cases this was coincident with
      endocytosis, but there was no statistically significant association between this
      expression and either endocytotic activity or the phase of the menstrual cycle.
      Results demonstrate that the epithelium of the human oviduct exhibits endocytic
      properties towards luminal soluble and particle antigens, which is not related
      either to MHC class II expression or to the phase of the menstrual cycle.

PMID- 9647541
TI  - Reactivity of human trophoblast monoclonal antibodies with marmoset monkey
      trophoblast cultures.
AB  - The aim of this study was to determine whether cultured trophoblast tissues,
      derived from the trophectoderm of marmoset monkey blastocysts, contain homologues
      of human trophoblast antigens. This is an essential prerequisite to determine
      whether the marmoset may be a suitable model for preclinical testing of a human
      antitrophoblast antigen for fertility regulation. Previously evaluated monoclonal
      antibodies from the Flinders University laboratory, which reacted with human
      trophoblast with a high degree of specificity, were tested for
      immunohistochemical reactivity using an immunoperoxidase detection method on both
      frozen and paraformaldehyde-fixed sections of the cultured marmoset monkey
      trophoblast. All monoclonal antibodies raised against human placenta reacted
      positively, when compared to controls, suggesting that human and marmoset
      trophoblast cells share common epitopes. The specificity of the monoclonal
      antibodies was investigated by determining whether there was cross-reactivity
      with other marmoset monkey tissues, including adrenal, spleen, kidney, liver,
      muscle, ovary and testis. The specificities of the monoclonal antibodies on these
      marmoset tissues were similar to those previously found on the corresponding
      human tissues. We have concluded that marmoset monkey trophoblast exhibits
      homologues of human trophoblast antigens. The findings also suggest that marmoset
      monkeys should be evaluated further as a primate model to test suitable target
      antigens for antitrophoblast vaccines that may be useful contragestation agents
      in humans.

PMID- 9647542
TI  - Circulating antibodies to a conserved epitope of the Chlamydia trachomatis 60 kDa
      heat shock protein (hsp60) in infertile couples and its relationship to
      antibodies to C.trachomatis surface antigens and the Escherichia coli and human
      HSP60.
AB  - To evaluate the relationship between immunity to specific regions of the
      Chlamydia trachomatis 60 kDa heat shock protein (hsp60), autoimmunity to human
      HSP60 and infertility, sera from 50 women and 45 men seen for an infertility
      evaluation were tested. Humoral immunity to human HSP60 was detected in 18% of
      women and 8.9% of men while antibodies to the Escherichia coli hsp60 were
      detected in 12% of women and 4.4% of men. These differences were not
      statistically significant. In contrast, antibodies to a synthetic peptide epitope
      of the chlamydial hsp60, encompassing amino acids 260-271 (chsp 260-271), were
      present in sera from 16 (32%) of the women but in only six (13.3%) of the men
      (P=0.03). Antibodies to chsp 260-271 were present in 11 out of 17 (64.7%)
      individuals with high titre (>1:160) immunoglobulin (Ig)G antibody to
      C.trachomatis surface antigens as opposed to only two out of 15 (13.3%) with low
      titre antibody and two out of of 17 (11.8%) with undetectable chlamydial antibody
      (P < 0.004). Antibodies to chsp 260-271 were also associated with humoral
      immunity to human HSP60. 50% of sera with, as opposed to only 18.6% of sera
      without, anti-human HSP60 IgG were positive for antibodies to chsp 260-271
      (P=0.03). In contrast, there was no relationship found between immunity to the
      E.coli hsp60 and antibodies to human HSP60. Antibodies to chsp 260-271 were more
      prevalent in women with at least two spontaneous abortions (eight out of 13,
      61.5%) than in women with other infertility diagnoses (six out of 35, 17.1%)
      (P=0.004). Thus, immunity to chsp 260-271 is more prevalent in women than in men,
      associated with autoimmunity to human HSP60 and may be an immunological marker
      for spontaneous abortion.

PMID- 9647543
TI  - Antiphospholipid antibodies and the outcome of pregnancy after the first in-vitro
      fertilization and embryo transfer cycle.
AB  - Increased antiphospholipid antibody prevalence has been demonstrated by a number
      of recent studies in in-vitro fertilization (IVF) patients but the potential
      effects of antiphospholipid antibodies on the different components of the
      reproductive process and the consideration of whether to test IVF patients for
      antiphospholipid antibodies are controversial. The present study was undertaken
      to investigate the possible association between the presence of circulating
      antiphospholipid antibodies (namely the lupus anticoagulant and anticardiolipin
      antibodies), among a series of 21 consecutive IVF patients having a clinical
      spontaneous abortion after their first embryo transfer. As a control group
      (n=42), the nearest IVF cycle resulting in an ongoing pregnancy before and after
      each miscarried IVF cycle (i.e. the closest cycles in temporal relationship to
      the index cycle) was used. One patient (4.8%) in the study group and two women
      (4.8%) among controls were seropositive for antiphospholipid antibodies. These
      low and similar seropositivity rates found in the two groups studied lead us to
      conclude that antiphospholipid antibodies testing in IVF patients should be
      considered only in those women having repeated failures of implantation/clinical
      abortion after embryo transfer but not in an infertile general population
      reaching an IVF programme.

PMID- 9647544
TI  - Fragile X premutation screening in women with premature ovarian failure.
AB  - We have screened 132 women with premature ovarian failure for fragile X (FRAXA)
      premutations. Three out of 23 (13%) pedigrees with the familial premature ovarian
      failure and 3/106 (3%) of women with the sporadic form of premature ovarian
      failure have FRAXA premutations compared with an expected prevalence of 1:590
      (P=0.02). The mechanism of the association between FRAXA premutations and
      premature ovarian failure is unknown but as a genetic marker, FRAXA screening
      will be particularly valuable in predicting premature ovarian failure in some
      pedigrees and in the identification of families at risk of transmitting fragile X
      syndrome.

PMID- 9647545
TI  - Hysteroscopic septum resection in patients with recurrent abortions or
      infertility.
AB  - Fifty-seven patients who underwent hysteroscopic septum resection between January
      1991 and December 1996 were studied; nine patients presented with recurrent
      abortions, 46 with infertility (26 primary and 20 secondary), one with
      dysmenorrhoea and one with an asymptomatic complete septum. Their reproductive
      history included 78 pregnancies: 69 (88.4%) abortions, two (2.6%) ectopics, two
      (2.6%) preterm deliveries and five (6.4%) term deliveries. In patients with
      infertility, the incidence of unexplained infertility was 19.6% and the incidence
      of endometriosis was 26.1%. After hysteroscopic septum resection, 42 patients
      were interested in pregnancy. All patients with recurrent abortions conceived
      spontaneously. Twenty-one (63.6%) infertile patients achieved a pregnancy, 13
      (61.9%) of them after treatment with various assisted reproduction techniques.
      The reproductive outcome after septum resection yielded 44 pregnancies, including
      three sets of twins and one set of triplets reduced to twins: 11 (25%) abortions,
      one (2.3%) ectopic pregnancy, two (4.5%) preterm deliveries (both twins), 28
      (63.7%) term deliveries and two (4.5%) as-yet ongoing pregnancies. It seems that
      the hysteroscopic treatment of uterine septum has a beneficial effect on
      pregnancy outcome. A septate uterus does not seem to be an infertility factor.
      The achievement of pregnancy is normal in patients with recurrent abortions,
      while the chances of conception in patients with infertility seem to be similar
      to those for the general infertile population.

PMID- 9647546
TI  - The role of monocyte chemotactic protein-1 in intraperitoneal adhesion formation.
AB  - Abdomino-pelvic adhesions arise from infection, endometriosis, or peritoneal
      injury during surgery, and represent a significant source of morbidity in women
      of reproductive age. Monocyte chemotactic protein-1 (MCP-1) plays a role in the
      chemotaxis of mononuclear cells and fibroblasts in a murine wound repair model.
      To evaluate the role of MCP-1 in intraperitoneal adhesion formation, we
      investigated peritoneal fluid MCP-1 levels of women undergoing laparoscopy.
      Patients without endometriosis were divided into two groups: normal fertile women
      undergoing bilateral tubal ligation without intraperitoneal adhesions (n=14) and
      women with pelvic adhesions (n=8). Patients with endometriosis were arranged into
      two groups: women with (n=17) and without (n=17) adhesions. Peritoneal fluid MCP
      1 levels were quantified using an enzyme-linked immunosorbent assay (ELISA).
      Peritoneal biopsy samples were immunostained for the detection of MCP-1 protein
      and macrophages, and were also processed for the presence of MCP-1 mRNA
      expression. Among women without endometriosis, the median peritoneal fluid MCP-1
      level was 144 pg/ml (range 54-261) in women without adhesions and was 336 pg/ml
      (range 130-2494) in women with adhesions (P=0.01). There was a significant
      correlation between adhesion scores and MCP-1 levels (r=0.50; P=0.018). Among
      women with endometriosis, peritoneal fluid MCP-1 levels significantly correlated
      with the stage of the disease. The presence or absence of adhesions did not
      significantly affect the peritoneal fluid MCP-1 levels in this group of women. In
      summary, we have found that women with adhesions have elevated peritoneal fluid
      MCP-1 levels. However, we were not able to show an incremental effect of
      adhesions on peritoneal fluid MCP-1 levels of patients with endometriosis. Thus,
      we conclude that factors besides the intraperitoneal adhesions contribute to the
      elevated peritoneal fluid MCP-1 levels in patients with endometriosis.

PMID- 9647547
TI  - Cost considerations with infertility therapy: outcome and cost comparison between
      health maintenance organization and preferred provider organization care based on
      physician and facility cost.
AB  - Of 98 retrospectively selected patient couples insured under one scheme (group I)
      who, based on performance of a hysterosalpingogram (HSG), were assumed to be
      under active infertility care, 96 were confirmed as infertile. These were matched
      by date, patient age and time of HSG to 96 patients under infertility care (group
      II). Both patient populations were then prospectively evaluated for outcome and
      cost of treatment. Total physician charges for groups I and II were similar.
      However, charges per achieved clinical pregnancy were higher in group I than
      group II since group I patients demonstrated a lower pregnancy rate (28/96, 29%)
      than group II patients (41/96, 43%) (P=0.05). Within group I, pregnancy rates
      were identical, whether treatment was provided by generalists or subspecialists.
      In group II, all care was provided by specialists. The number of days of
      treatment did not vary between groups I and H, though generalists in group I
      provided significantly fewer treatment days than specialists in either group I
      (P=0.003) or in group II (P=0.021). This was primarily due to a significantly
      higher patient drop-out rate in group I patients, and especially amongst those
      who received care from generalists (P < 0.0019). Group I patients also
      encountered significantly more surgical procedures than group H patients
      (P=0.0016). If physician charges are discounted and customary surgical facility
      costs are added, the actual cost structure for fertility care in group I patients
      was dramatically higher than in group II patients. The most cost-effective format
      to provide infertility care of high quality appears to be a managed care setting
      in which subspecialists provide a majority of care and in which patient choice is
      restricted to those subspecialists.

PMID- 9647548
TI  - Treatment-independent pregnancy rate in patients with severe reproductive
      disorders.
AB  - A long waiting list for in-vitro fertilization (IVF) offers the possibility to
      study treatment-independent pregnancy rates in patients with severe reproductive
      disorders. We performed a retrospective cohort study with a nested case-control
      design in which the cases achieved a spontaneous pregnancy while on the waiting
      list for IVF, or for IVF with intracytoplasmic sperm injection (ICSI), and the
      controls did not become pregnant while on the waiting list. Spontaneous
      pregnancies occurred in 76 of 1391 patients on the waiting list. Significant
      differences between pregnant and non-pregnant patients were found for duration of
      subfertility (couples on the IVF waiting list), and for progressive sperm
      motility and basal 17beta-oestradiol (couples on the ICSI waiting list). The 12
      months cumulative pregnancy rate for patients on the waiting list was 2.4% (95%
      CI 1.2-3.9%) for tubal subfertility patients, 5.9 % (3.7-8.7%) for longstanding
      unexplained subfertility patients, and 6.6% (4.5-9.3%) for male subfertility
      patients. Of the 76 control patients, 21% of tubal subfertility patients, 18% of
      unexplained subfertility patients, and 17% of male subfertility patients achieved
      a pregnancy in their first IVF or ICSI treatment cycle. We confirm that the
      treatment-independent pregnancy rate in patients with severe reproductive
      disorders is low. More than 75% of the spontaneous pregnancies in the tubal
      subfertility and unexplained subfertility couples occurred during their first
      three months on the waiting list, whereas spontaneous pregnancy rate in male
      subfertility couples showed a more gradual but persisting increase. We conclude
      that one cycle of IVF or ICSI is superior to 12 months of expectant management in
      patients with severely impaired fertility due to tubal, unexplained or male
      factors.

PMID- 9647549
TI  - Progestin receptor isoforms and prostaglandin dehydrogenase in the endometrium of
      women using a levonorgestrel-releasing intrauterine system.
AB  - This study has examined endometrial tissue in 14 normal women prior to insertion
      of a levonorgestrel-releasing intrauterine system (LNG-IUS) and thereafter
      longitudinally for up to 12 months post-insertion. The specific endpoints
      examined by immunohistochemistry were progesterone receptor (PR) subtypes A + B,
      oestrogen receptor (ER) and prostaglandin dehydrogenase (PGDH). Two
      antiprogesterone receptor antibodies, one specific to PR(B) subtype and the other
      to PR subtype A + B, were employed to examine the localization of both PR
      isoforms. The activity of PGDH, a progesterone dependent enzyme, was also
      measured. ER and PR(A+B) and PR subtype B were significantly down-regulated in
      glands and stroma in the presence of continuous intrauterine LNG delivery. There
      was an apparent increase in PR(A) immunoreactivity in endometrial glands between
      6 and 12 months post-insertion. Consistent with down-regulation of both isoforms
      of PR was reduced glandular PGDH immunostaining following LNG-IUS insertion, and
      PGDH activity (as measured by metabolism of excess substrate in vitro).
      Furthermore, PGDH activity, known to be localized in the glands, significantly
      increased (P < 0.05) at 12 months post-insertion, coinciding with the observed
      increase in glandular PR(A+B) immunoreactivity at this time. Since the LNG-IUS
      suppresses the PR(B) so strongly, PR(A) is likely to be the subtype that mediates
      long term LNG action in the endometrium. PR(B) is the more suppressed of the two
      subtypes, and only PR(A) rises along with PGDH activity. Alterations to normal
      endometrial morphology and function, e.g. perturbation of normal sex steroid
      receptor expression, following exposure to high concentrations of local LNG, may
      play a role in the aetiology of bleeding disorders associated with the LNG-IUS.
      Further elucidation of local uterine mediators involved in the mechanism of
      bleeding problems is required.

PMID- 9647550
TI  - Morphological and functional features of endometrial decidualization following
      long-term intrauterine levonorgestrel delivery.
AB  - Irregular bleeding remains a common reason for the discontinuation of progestin
      only contraception. The levonorgestrel releasing intrauterine system (LNG-IUS)
      has profound morphological effects upon the endometrium. Specific features are
      gland atrophy and extensive decidual transformation of the stroma. Morphological
      changes in the endometrium may be associated with perturbation of mechanisms
      regulating normal endometrial function. This study describes endometrial stromal
      and glandular features prior to and up to 12 months following insertion of the
      LNG-IUS. Comparison is made with first trimester decidua. In order to elucidate
      further mechanisms governing endometrial function with local intrauterine
      delivery of LNG, we here report histological features consistent with
      decidualization; a significant increase in granulocyte-macrophage colony
      stimulating factor (GM-CSF) immunoreactivity in decidualized stromal cells;
      glandular and stromal prolactin receptor expression and an infiltrate of CD56 +
      large granular lymphocytes and CD68 + macrophages. We are unaware of previous
      reports which have documented longitudinally both morphological and functional
      observations in endometrium exposed to local intrauterine levonorgestrel
      delivery. These studies demonstrate that long-term administration of intrauterine
      levonorgestrel results in features of altered morphology and function. No
      correlation was apparent between the end points in the study and the bleeding
      patterns described by the subjects. Further evaluation of these features in the
      context of menstrual bleeding experience may contribute to a better understanding
      of this troublesome side-effect which often leads to dissatisfaction and
      discontinuation of the intrauterine system.

PMID- 9647551
TI  - Low dose of cyproterone acetate and testosterone enanthate for contraception in
      men.
AB  - After a control phase, 10 normal men received cyproterone acetate (CPA) at a dose
      of 25 mg/day (CPA-25; n=5) or 12.5 mg/day (CPA-12.5; n=5) plus testosterone
      enanthate (TE) 100 mg/week, for 16 weeks. Throughout the study sperm counts were
      performed every 2 weeks, and luteinizing hormone (LH), follicle stimulating
      hormone (FSH), testosterone, biochemical and haematological tests were performed
      every 4 weeks. All five men in group CPA-25 and three men in group CPA-12.5
      achieved azoospermia. One man in group CPA-25 was azoospermic by week 12 of
      hormone administration, but had a sperm count of 0.1 x 10(6)/ml at week 16. Time
      to azoospermia was 9.0+/-1.3 and 8.7+/-0.7 weeks in groups CPA-25 and CPA-12.5
      respectively. Gonadotrophins were decreased by week 4 of hormone administration,
      remained around the minimum detectability of the assay for the duration of
      hormone administration and returned to baseline after stopping hormone
      administration. Testosterone values did not change. No change in any biochemical
      parameters was found. Haematological parameters were decreased at week 16 of
      hormone administration and returned to baseline after stopping hormone
      administration. In conclusion, these results suggest that an hormonal regimen
      consisting of testosterone plus a progestin with anti-androgenic properties holds
      promise as an effective, safe and reversible male contraceptive.

PMID- 9647552
TI  - Successful testicular sperm extraction (TESE) in spite of high serum follicle
      stimulating hormone and azoospermia: correlation between testicular morphology,
      TESE results, semen analysis and serum hormone values in 103 infertile men.
AB  - Spermatozoa recovered from testicular biopsies can be used through
      intracytoplasmic sperm injection (ICSI) to achieve a pregnancy. To assess the
      likelihood of successful testicular sperm extraction (TESE) in men suffering from
      severe oligo- or azoospermia, bilateral biopsy specimens were obtained. Following
      semi-thin sectioning, the morphology of testicular samples was graded according
      to a modified Johnsen score. TESE was performed in parallel to this histological
      examination. The number of isolated spermatozoa was assessed in a
      semiquantitative way. From 103 patients investigated, 64 (62.1%) showed
      azoospermia in a preceding semen analysis and 29 (28.2%) patients had sperm
      concentrations between 0.1 and 1 x 10(6)/ml. In 10 patients who had higher sperm
      counts, most spermatozoa were non-motile. Spermatozoa could be detected after
      TESE in the testicular tissue of 49 (77%) azoospermic men. When follicle
      stimulating hormone (FSH) concentration was normal, most patients had detectable
      spermatozoa after TESE. Nearly one-third of patients with mildly elevated FSH had
      no spermatozoa. Thirty-nine percent of patients in whom FSH was elevated to more
      than twice normal and 50% of patients with grossly elevated FSH had no detectable
      spermatozoa. In all, 82.8% of men with sperm concentrations between 0.1 and
      1x10(6)/ml in their ejaculate showed spermatozoa in the tissue sample after TESE.
      Our data demonstrate that, contrary to previous recommendations, infertile men
      with azoospermia and high FSH values should be reconsidered for testicular
      biopsy, provided that tissue samples can be cryopreserved for later TESE/ICSI
      treatment.

PMID- 9647553
TI  - A logistic regression model including DNA status and morphology of spermatozoa
      for prediction of fertilization in vitro.
AB  - To determine predictive values of routine semen analysis, sperm morphology
      evaluation using strict criteria and DNA status for in-vitro fertilization (IVF),
      66 consecutive couples undergoing IVF in a university hospital IVF programme were
      prospectively investigated. Semen samples from 66 men were evaluated by routine
      semen analysis, morphology evaluation using strict criteria and acridine orange
      staining for determination of DNA status. A new technique is described for
      acridine orange scoring which consisted of evaluation of two smears per case,
      with and without heat treatment. Resistance to heat-provoked denaturation was
      determined by the difference between two evaluations. A logistic regression model
      was built and receiver operating characteristic curves were constructed to
      determine the threshold values and to compare diagnostic properties. Morphology
      evaluation using strict criteria and concentration of progressively motile
      spermatozoa were found to be the principal parameters determining the sperm
      fertilizing capacity in vitro. The logistic regression model composed of
      morphology evaluation using strict criteria and acridine orange score had a
      powerful diagnostic capability for prediction of fertilization in vitro.

PMID- 9647554
TI  - The effects of antioxidant supplementation during Percoll preparation on human
      sperm DNA integrity.
AB  - The integrity of sperm DNA is crucial for the maintenance of genetic health. A
      major source of damage is reactive oxygen species (ROS) generation; therefore,
      antioxidants may afford protection to sperm DNA. The objectives of the study
      were, first, to measure the effects of antioxidant supplementation in vitro on
      endogenous DNA damage in spermatozoa using the single cell gel electrophoresis
      (comet) assay and, second, to assess the effect of antioxidant supplementation
      given prior to X-ray irradiation on induced DNA damage. Spermatozoa from 150
      patients were prepared by Percoll centrifugation in the presence of ascorbic acid
      (300, 600 microM), alpha tocopherol (30, 60 microM), urate (200, 400 microM), or
      acetyl cysteine (5, 10 microM). DNA damage was induced by 30 Gy X-irradiation.
      DNA strand breakage was measured using the comet assay. Sperm DNA was protected
      from DNA damage by ascorbic acid (600 microM), alpha tocopherol (30 and 60
      microM) and urate (400 microM). These antioxidants provided protection from
      subsequent DNA damage by X-ray irradiation. In contrast, acetyl cysteine or
      ascorbate and alpha tocopherol together induced further DNA damage.
      Supplementation in vitro with the antioxidants ascorbate, urate and alpha
      tocopherol separately has beneficial effects for sperm DNA integrity.

PMID- 9647555
TI  - Enhancement of motility and acrosome reaction in human spermatozoa: differential
      activation by type-specific phosphodiesterase inhibitors.
AB  - Inhibition of sperm phosphodiesterase (PDE) has been shown to increase cAMP
      concentrations and stimulate motility and the acrosome reaction. While several
      PDE genes exist in mammals, little is known about the physiological role of PDE
      forms expressed in human spermatozoa. Using type-selective inhibitors, we
      identified two of the PDE forms expressed in human spermatozoa and studied their
      involvement in sperm function. Selective inhibitors of calcium-calmodulin
      regulated PDE1 (8-methoxy-isobutyl-methylxanthine) and cAMP-specific PDE4 (RS
      25344, Rolipram) were used to study PDE forms in human sperm extracts. 8-MeIBMX
      and Rolipram/RS-25344 inhibited sperm PDE activity by 35-40 and 25-30%
      respectively. Subcellular fractionation of the sperm homogenate suggests these
      pharmacologically distinct forms may be located in separate cellular regions. To
      evaluate the functional significance of different PDE forms, the effect of type
      specific PDE inhibition on sperm motility and the acrosome reaction was examined.
      PDE4 inhibitors enhanced sperm motility over controls without affecting the
      acrosome reaction, while PDE1 inhibitors selectively stimulated the acrosome
      reaction. These data indicate at least two distinct PDE types exist in human
      spermatozoa. Our findings also support the hypothesis that PDE subtypes affect
      sperm function by regulating separate pools of cAMP and may ultimately offer
      novel treatments to infertile couples with abnormal semen parameters.

PMID- 9647556
TI  - Quantitative sperm mucus penetration: modified formulae for calculating
      penetration efficiency.
AB  - In 1980 Katz et al. derived a formula for the percentage of successful collisions
      (PSC) as a quantitative measure of sperm-cervical mucus penetration efficiency.
      The use of PSC waned after its validity was questioned by reports of values >100%
      and the observation that PSC varied with the cross-sectional area of the mucus
      column. The aim of the present study was to develop a more accurate measure of
      mucus penetration efficiency by correcting the original formula for the effects
      of sperm depletion in the semen reservoir. Two formulae were derived using
      different models for the sperm-mucus interaction: (i) each motile spermatozoon
      was assumed to have an equal chance of mucus penetration on collision; (ii) a
      select subpopulation of spermatozoa was assumed to penetrate with 100% efficiency
      on collision. Both modified formulae gave PSC values higher than the original
      estimates. Under the experimental conditions employed in this work, where large
      capillaries were used, the depletion corrections ranged from 4 to 46% (n=8, mean
      20%) for model (i) and from 190 to 320% (n=8, mean 250%) for model (ii). The
      invariance of PSC (ii) results with respect to capillary cross-sectional area
      (1.52 mm2, 31.1%; 5.4 mm2, 28.2%) suggests that the assumptions of model (ii)
      provide the more accurate description of the sperm-mucus interaction.

PMID- 9647557
TI  - The mini-micro-epididymal sperm aspiration for sperm retrieval: a study of
      urological outcomes.
AB  - Epididymal sperm aspiration and in-vitro fertilization (IVF) with
      intracytoplasmic sperm injection is an established treatment for obstructive
      azoospermia. Sperm aspiration is performed with either an incision or
      percutaneously. To control costs, minimize morbidity and retain the advantages of
      both approaches, we developed a mini-incision technique for epididymal aspiration
      and here report sperm retrieval and procedure-related outcomes. Twenty-six
      consecutive patients with obstructive azoospermia underwent epididymal sperm
      retrieval through a 1 cm incision with local anaesthesia to provide spermatozoa
      for concurrent IVF cycles. The quality of retrieved spermatozoa, the quantity of
      spermatozoa cryopreserved as well as anaesthetic requirement, recovery time and
      patient satisfaction were evaluated. Fresh epididymal spermatozoa were retrieved
      in 25 of 26 (96%) patients. In one patient, testicular sperm extraction was
      necessary. Excess motile spermatozoa were cryopreserved in 24 of 26 (92%)
      patients; a mean total motile count of 4.8x10(6) motile spermatozoa were banked.
      The procedure was performed with 62% of patients receiving minimal i.v. sedation.
      Post-procedure recovery was rapid, with a median time to return to work of 2.0
      days with a median of 2.0 pain pills taken. Procedure-related satisfaction was
      high. The mini-micro-epididymal sperm aspiration achieves the goals of reliable
      retrieval of abundant epididymal spermatozoa with a single, minimally morbid
      procedure. It appears to combine the advantages of the incision and percutaneous
      approaches.

PMID- 9647558
TI  - A comparison between open and percutaneous needle biopsies in men with
      azoospermia.
AB  - Open testicular biopsy is a classic method of investigation in men with
      azoospermia. Recently, percutaneous needle biopsy of the testis has been used in
      attempts to obtain material for histopathological diagnosis in such cases and to
      retrieve spermatozoa for intracytoplasmic sperm injection (ICSI). To determine
      whether a 19 gauge (G) and a 21G butterfly needle could be used for percutaneous
      aspiration of testicular tissue to determine the presence of mature spermatids
      and assess spermatogenesis, 10 patients (16 testes) and 12 patients (17 testes)
      underwent 19G or 21G needle biopsy respectively, immediately followed by open
      testicular biopsy, with both procedures under local anaesthesia. Biopsy with each
      needle size was compared with open biopsy. With the 19G needle, in the 14 cases
      where material was obtained there was full agreement with open biopsy regarding
      the presence or absence of mature spermatozoa, whereas with the 21G needle only
      nine of the 13 biopsies yielding material were predictive in this respect. Each
      needle size correlated poorly with open biopsy regarding evaluation of
      spermatogenesis. We conclude that percutaneous biopsy with a 19G butterfly needle
      is a quick and reliable method for demonstrating spermatozoa for ICSI. But for a
      detailed histopathological diagnosis, however, the needle biopsies gave poor
      results, whereas the material from the open testicular biopsies was assessable.

PMID- 9647559
TI  - Androgen action during male sex differentiation includes suppression of cranial
      suspensory ligament development.
AB  - The cranial suspensory ligament is located on the border of the cranial
      (mesonephric) mesentery in adult female mammals, which runs between the cranial
      pole of the internal genitalia and the dorsal abdominal wall. Absence of the
      cranial suspensory ligament in male mammals depends upon exposure of its
      primordium to fetal testicular androgens and is a prerequisite for testis
      descent. Female rats were exposed to 5alpha-dihydrotestosterone propionate at
      different stages of genital development, and cranial suspensory ligament
      development was studied in neonatal and in adult animals. Androgens suppressed
      cranial suspensory ligament development when exposure started during the early
      stages of genital development, until day 19 postconception (pc). Androgen
      receptor expression was immunohistochemically detected in the cranial mesentery
      of both sexes from day 16 pc onwards. A decrease of androgen receptor expression
      in female fetuses from day 18 pc onwards coincided with the appearance of a
      differentiated cranial suspensory ligament, as evidenced by the expression of two
      cell differentiation markers: alpha-smooth muscle (alpha-SM) actin and desmin.
      alpha-SM actin was located on the outer border of the cranial mesentery of both
      sexes at day 17 pc, and expression increased only in female fetuses. On day 19
      pc, desmin expression was also detectable in the a-SM actin-positive cells.
      Proliferation and apoptosis indices of cells in the cranial mesentery, as
      analysed by 5'-bromodeoxyuridine incorporation and by detection of DNA strand
      breaks (TUNEL method) respectively, did not show any difference between the
      sexes, neither on day 17 nor on day 18 pc. Since primordial cells of the cranial
      suspensory ligament highly express the androgen receptor during the period of
      gestation when androgens can suppress cranial suspensory development, altered
      morphogenesis of these cells may be a direct consequence of androgen action.

PMID- 9647560
TI  - Continuing the debate on empty follicle syndrome: can it be associated with
      normal bioavailability of beta-human chorionic gonadotrophin on the day of oocyte
      recovery?
AB  - This paper describes our experience with four ovarian stimulation in-vitro
      fertilization (IVF) cycles in which we failed to retrieve oocytes despite normal
      bioavailability of beta-human chorionic gonadotrophin (beta-HCG) in patients'
      blood 35 h after HCG administration. In three cases, the oocyte recovery
      procedure was interrupted, a second dose of HCG was administered and 24 h later
      mature oocytes were collected from two of the patients. In the first case, the
      three metaphase II oocytes collected fertilized after intracytoplasmic sperm
      injection (ICSI) and two cleaved grade three embryos were transferred but
      pregnancy did not ensue. In the second case, six out of eight metaphase II
      oocytes fertilized and cleaved following ICSI, leading to transfer of one grade
      two and two grade three embryos. This resulted in a clinical pregnancy which at
      the time of this report is ongoing. A similar rescue protocol was used for the
      third case who had empty follicle syndrome (EFS) in her previous treatment cycle
      but only cumulus-corona complexes were aspirated. Five additional patients who
      had EFS before instituting pregnancy diagnostic test screening have had further
      treatment cycles in which oocytes were collected but pregnancy did not ensue. We
      conclude that normal bioavailability of beta-HCG on the day of oocyte recovery
      does not exclude the diagnosis of EFS. EFS does not predict a reduced fertility
      potential in future cycles, although it may recur due to a biological abnormality
      in the availability of mature oocytes that are retrievable. In such patients,
      oocyte donation may offer the chance of achieving a pregnancy.

PMID- 9647561
TI  - Differential responses of granulosa cells from small and large follicles to
      follicle stimulating hormone (FSH) during the menstrual cycle and acyclicity:
      effects of tumour necrosis factor-alpha.
AB  - This study determined effects of follicle stimulating hormone (FSH) alone and in
      combination with tumour necrosis factor (TNF), on granulosa cells from small (5
      10 mm diameter) and large (>10-25 mm) follicles during follicular and luteal
      phases of the cycle and during periods of acyclicity. Granulosa cells were
      collected from ovaries of premenopausal women undergoing oophorectomy. The cells
      were cultured with human FSH (2 ng/ml) and testosterone (1 microM) in the
      presence or absence of human TNF-alpha (20 ng/ml). Media were removed at 48 and
      96 h after culture and progesterone, oestradiol and cAMP in media were measured
      by radioimmunoassays. FSH stimulated the accumulation of oestradiol from
      granulosa cells of small follicles during the follicular and luteal phases but
      not during acyclicity; and TNF reduced oestradiol accumulation in the presence of
      FSH. Interestingly, in granulosa cells from small follicles, progesterone and
      cAMP secretion increased in response to FSH and neither was affected by TNF.
      Thus, TNF specifically inhibited the conversion of testosterone to oestradiol in
      granulosa cells from small follicles. FSH stimulated oestradiol production by
      granulosa cells of large follicles obtained only during the follicular phase of
      the cycle and TNF inhibited the FSH-induced oestradiol secretion. Granulosa cells
      obtained from large follicles during the luteal phase and during acyclicity did
      not accumulate oestradiol in response to FSH. However, FSH increased progesterone
      and cAMP secretion by granulosa cells obtained from large follicles during the
      follicular and luteal phases. During the luteal phase alone, TNF in combination
      with FSH increased progesterone accumulation above that of FSH alone. FSH did not
      increase progesterone, oestradiol or cAMP secretion by granulosa cells obtained
      from large follicles during acyclicity. Thus, FSH increases progesterone,
      oestradiol and cAMP secretion by granulosa cells of small follicles during the
      follicular and luteal phases and TNF appears to inhibit FSH-induced oestradiol
      secretion specifically in those cells. In large follicles, FSH-stimulated
      granulosa cell secretion of oestradiol is limited to the follicular phase and
      this effect can be inhibited by TNF. In addition, when granulosa cells of large
      follicles do not increase oestradiol secretion in response to FSH, TNF stimulates
      progesterone secretion.

PMID- 9647562
TI  - Recombinant luteinizing hormone as a survival and differentiation factor
      increases oocyte maturation in recombinant follicle stimulating hormone
      supplemented mouse preantral follicle culture.
AB  - The effects of recombinant luteinizing hormone (rLH) and recombinant follicle
      stimulating hormone (rFSH) both separately and together were analysed on the in
      vitro maturation of a well-defined class of mouse early preantral follicles.
      Metaphase-II (MII) oocytes were only obtained when rLH or rFSH or a combination
      of both hormones was added to a standard rich culture medium at constant doses
      throughout the culture period. Without gonadotrophins only 8% of the follicles
      reached day 12 of culture. Follicle survival was optimal (between 90 and 100%)
      when rFSH was used; significantly fewer follicles were kept intact when rLH was
      added as the only supplement (54%; P < 0.001). Theca cells played a fundamental
      role in follicle survival when rLH was the only supplement. Presence of rLH
      significantly influenced the formation of antral-like cavities: on day 12, 59% of
      follicles cultured with rLH + rFSH had a large cavity, as compared with only 21%
      in cultures with rFSH only (P < 0.0001). The rHCG stimulated germinal vesicle
      breakdown rate from the different gonadotrophin-supplemented cultures on day 12
      was not significantly different (FSH: 89%; LH: 70%; FSH/LH: 83%). However,
      addition of rLH to rFSH did significantly improve (P < 0.05) the completion of
      the first meiotic division up to the MII stage (FSH: 46%; LH: 39%; FSH/LH: 76%).
      Interfollicle differences in steroid production were very large and depended on
      the presence of theca cells and on the kind of gonadotrophin supplemented.
      Without theca cells, oestrogen concentrations in rFSH-supplemented cultures were
      100 times lower than their theca-containing counterparts during the entire
      culture period. From culture day 9 onwards most conditioned media had increased
      basal progesterone concentrations. This study points up the in-vitro role of LH
      on the differentiation of follicle-like structures and the oocyte's meiotic
      maturation and suggests an important role for theca cells in providing modulators
      of in-vitro gonadotrophin action.

PMID- 9647563
TI  - Human ovarian granulosa cells and follicular fluid indices: the relationship to
      oocyte maturity and fertilization in vitro.
AB  - The study investigates the correlation between oocyte maturity and fertilization
      and a variety of hormonal parameters in follicular fluid and ovarian granulosa
      cells. A methodology for purification of granulosa cells from contaminating blood
      cells is also established. A total of 63 follicular aspirates were collected at
      oocyte retrieval from 30 women superovulated using the long luteinizing hormone
      releasing hormone (LHRH analogue)/human menopausal gonadotrophin regimen.
      Oestradiol, progesterone, testosterone and human chorionic gonadotrophin (HCG)
      were quantified in follicular fluid and granulosa cells were immunostained for
      human chorionic gonadotrophin. Immunopurification of granulosa cells from
      contaminating blood cells was performed. HCG in follicular fluid was
      significantly high in follicles yielding immature (grade 3) oocytes (P=0.002);
      there was no correlation with fertilization. Aspirates from follicles containing
      mature (grade 1) oocytes and oocytes that subsequently fertilized had
      significantly more granulosa cells immunobound to HCG (P < 0.001, P=0.02).
      Moreover, the immunomagnetic purification technique provided >98% pure population
      of granulosa cells. The data demonstrate that HCG in follicular fluid and on
      granulosa cells may help to predict oocyte maturity and fertilization.
      Furthermore, immunomagnetic beads provide a reliable procedure for the
      purification of ovarian granulosa cells.

PMID- 9647564
TI  - The impact of cellular fragmentation induced experimentally at different stages
      of mouse preimplantation development.
AB  - It has been demonstrated previously that removal of acellular debris from the
      preimplantation mouse embryo is beneficial for subsequent development to the
      hatched blastocyst stage. We have studied the impact of cellular fragmentation
      induced in the mouse embryo during the late pronuclei and 8-cell stages on the
      hatching frequency and total cell number at the blastocyst stage. At the late
      pronuclei stage about one-quarter of the cytoplasm was removed from embryos in
      the experimental group, in four to six steps, thus creating four to six
      cytoplasts that were subsequently returned as anucleated fragments under the zona
      pellucida. Embryos with one-quarter of the cytoplasm removed and with intact
      cytoplasm after partial zona dissection (PZD) served as controls. At the 8-cell
      stage, embryos with their nucleoplast removed from two blastomeres served as an
      experimental group. Groups of embryos with part of the cytoplast removed from two
      blastomeres (nucleated fragments), embryos with two blastomeres removed and
      embryos after PZD alone served as controls. After manipulation all embryos were
      left in culture and analysed at about 100 h after human chorionic gonadotrophin
      administration. Fragments induced at the late pronuclei stage did not participate
      in compaction and were often spontaneously expelled from the embryo during
      hatching. Neither embryo hatching rate nor total cell number was affected when
      compared with zygotes with reduced cytoplasm. Although both nucleated and
      anucleated fragments induced at the 8-cell stage participated in recompaction,
      hatching was not compromised and there was no interference in further development
      as assessed by the cell number or hatching rate at the blastocyst stage, as
      compared with embryos with blastomeres removed. We conclude that anucleated
      cellular fragments formed in an otherwise healthy embryo, both before and after
      acquisition of the ability for compaction, are benign and that their removal
      provides no benefit for embryo development, at least to the hatched blastocyst
      stage.

PMID- 9647565
TI  - Endogenous folic acid is essential for normal development of preimplantation
      embryos.
AB  - Preimplantation mammalian embryos develop with a high degree of autonomy. To
      date, there have been no unequivocal demonstrations of a requirement for vitamins
      in preimplantation embryo development. Reduced folic acid acts as an important
      methyl donor in many reactions including the synthesis of thymidine. Thymidine
      does not accumulate in cells so it might be expected that significant amounts of
      reduced folate would be required to support the exponential increase in DNA
      synthesis that occurs during early embryo development. The reduction of folate is
      catalysed by dihydrofolate reductase (EC 1.5.1.3) which is selectively inhibited
      by the anti-cancer drug methotrexate. Methotrexate caused a dose-dependent
      inhibition of cell division in 1-cell, 2-cell and 8-cell mouse embryos with 50%
      inhibition of division occurring at concentrations of 1-10 microM. At a
      concentration of 0.1 microM only minimal inhibition of the initial cell division
      occurred, but continuous culture in this concentration of methotrexate completely
      inhibited further cell divisions. This suggests that most of the exogenous store
      of reduced folates was used in the first round of cell division. The effects of
      methotrexate were apparently primarily due to thymidine starvation, since a 10
      fold excess of thymidine over methotrexate in culture media reversed the
      inhibition of development. Supplementing media with folic acid had no beneficial
      effect on the rate at which zygotes produced by in-vitro fertilization developed
      to the blastocyst stage. It is concluded that the development of the early embryo
      has an absolute requirement for reduced folate for thymidine synthesis which is
      met entirely by endogenous sources.

PMID- 9647566
TI  - DNA strand breaks and phosphatidylserine redistribution in newly ovulated and
      cultured mouse and human oocytes: occurrence and relationship to apoptosis.
AB  - This study determined the occurrence of two molecular markers of apoptosis,
      chromosomal DNA strand breaks and oolemma phosphatidylserine redistribution, in
      >200 uninseminated and unfertilized human oocytes, and >800 newly ovulated and
      cultured mouse oocytes. DNA breaks were analysed by terminal deoxynucleotidyl
      transferase-mediated dUDP nick-end labelling (TUNEL) and phosphatidylserine by
      annexin V staining, with imaging by conventional epifluorescence and scanning
      laser confocal fluorescence microscopy. More than 300 intact and 500 fragmented
      mouse oocytes were examined at 24 h intervals during 6 days of culture in three
      different types of medium. For the human, 205 oocytes were examined at retrieval
      or at 24 h intervals during 7.5 days of culture in two types of medium. The
      perifollicular vascularity and the dissolved oxygen content of follicular fluid
      were determined for most of the follicles from which human oocytes were derived.
      The results demonstrate that TUNEL fluorescence of metaphase II (MII) chromosomes
      and annexin V staining of the oolemma in newly ovulated and cultured mouse and
      human oocytes are rare, and, when detected, are not spatially or temporally
      related. This finding also applied to mouse oocytes that fragmented during
      culture and exhibited morphological features that grossly resembled apoptotic
      body formation. In contrast, TUNEL but not annexin V staining occurred in the
      first polar body of a relatively high proportion of newly ovulated mouse oocytes,
      but was rarely detected in newly aspirated human oocytes. For the human, the
      occurrence of MII chromosomal TUNEL fluorescence was patient-specific and
      unrelated to perifollicular vascularity or dissolved oxygen content of the
      corresponding follicular fluid. The pattern of chromosomal TUNEL fluorescence
      observed in the first polar body and in the MII chromosomes of a very small
      number of mouse and human oocytes, especially after many days of culture,
      suggests that DNA strand breaks may not arise by apoptosis-associated
      endonuclease digestion. The results with these two markers suggest that it is
      premature to conclude that apoptosis occurs in ovulated oocytes or that such a
      mechanism is involved in the elimination or prevention of fertilization of
      oocytes with cytoplasmic or chromosomal defects.

PMID- 9647567
TI  - The effects of co-culture with human fibroblasts on human embryo development in
      vitro and implantation.
AB  - In a human in-vitro fertilization (IVF) programme, the effect of co-culture of
      embryos with human fibroblasts was evaluated with respect to pregnancy rate and
      embryo development. Patients were included in the study after giving informed
      written consent. The IVF treatments were randomly assigned by stratification of
      both age (<36 versus > or =36 years) and previous IVF attempts (yes versus no).
      After fertilization was established, the zygotes were transferred to a 4-well
      dish with or without fibroblasts and cultured for 2 days. On the third day after
      ovum pick-up (OPU), cell number and quality [5 (good) to 1 (poor)] of the embryos
      were scored and a maximum of three embryos was transferred. Supernumerary embryos
      of good quality were cryopreserved. The design of this study was a group
      sequential trial with the objective of detecting differences between pregnancy
      rates following IVF with conventional incubation or incubation in co-culture with
      fibroblasts. This design included one evaluation at half-way data collection. In
      the study, 148 patients had an OPU, of whom 77 were allocated to the co-culture
      group. There was no statistically significant difference in pregnancy rate, cell
      number and embryo quality between the two groups. The ongoing pregnancy rate per
      embryo transfer was 27% in co-culture and 30% in the conventional culture group.
      The implantation rates per transferred embryo were 17 and 18% respectively. Using
      a multivariate logistic regression model for the probability of ongoing
      pregnancies, the odds ratio of co-culture, adjusted for age and previous IVF
      attempts, was not statistically significant. In conclusion, co-culture with human
      fibroblasts does not contribute to an improvement of embryo quality nor to a
      higher pregnancy rate after IVF in an unselected group of patients.

PMID- 9647568
TI  - Rescue of implantation potential in embryos with poor prognosis by assisted zona
      hatching.
AB  - The effect of the assisted zona hatching (AZH) procedure was investigated on 135
      cycles with a poor prognosis of pregnancy due to: (i) maternal age > or = 38
      years (45 cycles); (ii) three or more failed in-vitro fertilization (IVF)
      attempts (70 cycles), and (iii) patients possessing both inclusion criteria (20
      cycles). The control groups (113 cycles) included patients possessing the same
      characteristics (42, 53 and 18 cycles respectively) and who did not undergo the
      AZH procedure. A total of 505 embryos was treated with AZH before transfer,
      resulting in: 14, 25 and 6 clinical pregnancies. The percentage of clinical
      pregnancies per cycle was significantly higher than controls for the first (31 vs
      10% in control 1, P < 0.05) and second groups (36 vs 17% in control 2, P < 0.05).
      No significant difference in percentage of clinical pregnancies was found for the
      third group (30 vs 6%). Similarly, higher rates of implantation were obtained
      (11.5, 15 and 11%) compared to the respective controls (4%, P < 0.02; 6.3%, P <
      0.01; and 1.5%). The rate of miscarriage in the AZH groups was similar to that
      obtained in the controls (22 vs 21%). Finally, the morphological analysis of the
      embryos transferred revealed that the poor prognosis condition is associated to a
      significantly slower rate of development and a higher rate of fragmentation. The
      present results indicate that AZH procedure improves pregnancy and implantation
      rates in patients with a poor prognosis of pregnancy by facilitating the hatching
      process in embryos which would otherwise be trapped inside the zona pellucida.

PMID- 9647569
TI  - Chromatin decondensation, pronucleus formation, metaphase entry and chromosome
      complements of human spermatozoa after intracytoplasmic sperm injection into
      hamster oocytes.
AB  - Obtaining karyotypes from human spermatozoa after microinjection into Syrian
      golden hamster oocytes is difficult and the hitherto reported results are
      unsatisfactory. This may be related to the injection and culture technique or to
      the high susceptibility of the hamster oocytes to undergo parthenogenetic
      activation or both. Therefore, we investigated the hamster oocyte-human sperm
      microinjection model using the following two approaches: (i) application of
      contemporary techniques for injection (touching the sperm tail) and culture
      (hamster embryo culture medium, HECM-3, 10% CO2) and (ii) omission of Ca2+ from
      the injection medium. Thus, in the first series of experiments, 252 hamster
      oocytes were injected with human spermatozoa. Among the 219 (87%) oocytes that
      survived the injection procedure, the mean percentages of male pronucleus
      formation [two pronuclei (2PN), two polar bodies (PB)], mitotic metaphase entry
      and sperm chromosome spreads were 41.4, 27.8 and 18.2% respectively. Analysis of
      the oocytes which failed to develop the male pronucleus following injection
      revealed that most of them had developed only the hamster female PN while the
      sperm nuclei were either intact or swollen (partially decondensed), indicating
      that failure of oocyte activation was not the likely reason for the failure of
      male PN formation in these oocytes. In the next series of experiments, sibling
      oocytes were alternately injected with spermatozoa suspended either in the
      regular (1.9 mM Ca2+) or Ca2+-free injection medium (experiment set 2, n=278). A
      significant improvement was noted in the mean percentages of oocytes with 2PN,
      2PB, metaphase entry and sperm chromosome spreads in the Ca2+-free group versus
      the regular group (2PN, 2PB: 51 versus 36.6%, metaphase entry: 36.3 versus 26.9%
      and sperm chromosome spreads: 28 versus 20.4%; all P < 0.04). Thus,
      parthenogenetic activation appears to be one of the contributing factors for the
      failure of male PN formation after heterospecific hamster ICSI. From these
      experiments it can be concluded that application of the advanced injection and
      culture techniques and omission of Ca2+ from the injection medium are promising
      for the routine application of the hamster oocyte microinjection for karyotyping
      of human spermatozoa with poor fertilizing capacity.

PMID- 9647570
TI  - Expression of cadherins and CD44 isoforms in ovarian endometrial cysts.
AB  - We evaluated the immunohistochemical expression of cadherins and CD44 variants in
      20 endometriomas, 20 cystadenomas, 20 borderline ovarian tumours as well as 20
      ovarian carcinomas, and the serological and cystic fluid concentrations of
      soluble E-cadherin and soluble CD44 standard (sCD44sdt) in 20 endometriomas, 20
      cystadenomas, six borderline and 11 carcinomas of the ovary. In endometriomas,
      immunostaining of E- and N-cadherin was negative (20 and 30% respectively). CD44
      H, v3 and v6 immunostaining were detected in 63, 10 and 40% respectively. A
      difference in immunostaining for E-cadherin was found between endometriomas and
      cystadenomas (P < 0.001) and for N-cadherin between endometriomas and carcinomas
      (P < 0.001). A difference in CD44H immunostaining was observed between
      endometriomas and cystadenomas (P < 0.035) but not with borderline ovarian
      tumours and carcinomas. No difference in serum concentrations of soluble E
      cadherins and CD44 standard was found between the four groups of tumours. Cystic
      fluid concentrations of E-cadherin were lower in endometriomas than in borderline
      tumours and ovarian carcinomas (P < 0.001). High concentrations of soluble CD44
      standard cystic fluid were found in endometriomas than in other ovarian cysts.
      Endometriomas and borderline tumours share alterations of cadherins and CD44
      isoforms which may help in the understanding of the aggressive and invasive
      potentials of endometriotic cells.

PMID- 9647571
TI  - The effect of lignocaine on sperm phagocytosis in the peritoneal fluid from women
      with or without endometriosis.
AB  - The study was undertaken to investigate a possible mechanism for reducing the
      phagocytosis of spermatozoa by leukocytes in the peritoneal fluid from women
      suffering from endometriosis. Peritoneal fluids were collected during laparoscopy
      from women undergoing laparoscopic sterilization or from women under
      investigation for cause of infertility where the laparoscopic findings were
      endometriosis. Prepared spermatozoa from one healthy man were incubated in vitro
      with peritoneal fluid with or without lignocaine. Samples from the incubations
      were studied daily and the number of viable and dead spermatozoa were counted.
      The number of free spermatozoa, not adhered to leukocytes, was significantly
      increased when incubated in human peritoneal fluid supplemented with lignocaine.
      Thus lignocaine contributes to increasing the number of free spermatozoa and
      maintaining the possibility of fertilizing an oocyte. For patients with
      endometriosis, treatment with lignocaine might be a means of increasing the
      chances of conception. A clinical study is in progress to evaluate this effect in
      vivo and to search for alternative methods of assisting the fertilization
      process.

PMID- 9647572
TI  - Endometriosis and uterine leiomyomata with ovarian granulosa cell tumour.
AB  - We report the first known case of right endometrial cyst and multiple uterine
      leiomyomata complicated by an ovarian granulosa cell tumour of adult type. A 42
      year old woman had an adult type left granulosa cell tumour. Laparoscopy 13 years
      earlier had revealed a small endometrial implant on the peritoneum, without
      uterine leiomyomata or bilateral ovarian tumours. Findings in this case suggest
      that the aetiology of endometriosis and uterine leiomyomata are related to the
      presence of an oestrogen-secreting neoplasm and that the presence of a state of
      hyperoestrogenaemia due to granulosa cell tumour over several years might have
      stimulated the development of endometriosis and leiomyomata.

PMID- 9647573
TI  - Pregnancy augments nitric oxide-dependent dilator response to acetylcholine in
      the human uterine artery.
AB  - The influence of pregnancy on the dilator effects of acetylcholine in the
      isolated human uterine artery was investigated. Acetylcholine (0.1 nM to 0.1
      microM) produced concentration- and endothelium-dependent relaxation of
      norepinephrine (3 microM)-induced contraction. The relaxation was greater in
      arteries from pregnant patients (P arteries) than from non-pregnant patients (NP
      arteries). The maximal relaxation was 53.5+/-3.4% (n=21) in P arteries and 23.5+/
      2.5% (n=35) in NP arteries. In both P and NP arteries the cholinergic relaxation
      was increased in the presence of superoxide dismutase and greatly reduced in the
      presence of the nitric oxide synthase inhibitors, NG-mono-methyl L-arginine (L
      NMMA) and L-nitro-arginine-methylester (L-NAME). The effect of these nitric oxide
      synthase inhibitors was reversed by L-arginine. We conclude that pregnancy
      enhances acetylcholine-induced nitric oxide synthesis and release in the human
      uterine artery.

PMID- 9647574
TI  - Sex hormone-binding globulin stimulates chorionic gonadotrophin secretion from
      human cytotrophoblasts in culture.
AB  - The effects of sex hormone-binding globulin (SHBG) on the secretion of human
      chorionic gonadotrophin (HCG) and cAMP by cultured human cytotrophoblasts were
      investigated. Cytotrophoblasts obtained from normal term placentae were cultured
      in serum-free medium with or without the addition of human SHBG. The presence of
      SHBG in the medium increased the release of HCG and the accumulation of cAMP.
      Ligand-free SHBG was able to raise both HCG and cAMP concentrations and the
      maximal response was observed with 1 nM of the steroid-binding globulin. Addition
      of either oestradiol or 5alpha-dihydro-testosterone (DHT) to cultures previously
      incubated with SHBG in a final molar ratio of 1:10 resulted in a further increase
      of HCG and cAMP concentrations. This effect was blocked when cultured placental
      cells were exposed to SHBG that was previously saturated with DHT or when
      incubated in the presence of steroids only. The results of the present study
      provide evidence for the in-vitro regulation of HCG secretion by SHBG and further
      support the concept that this steroid-binding protein may act as a mediator of
      steroid action at the cellular level. Finally, the increase in cAMP suggests that
      SHBG receptor located in the surface of syncytiotrophoblast membranes is coupled
      to adenylate cyclase as part of the G-protein receptor family. Our results may
      provide new insights into the biological implications of extracellular steroid
      binding proteins as well as new perspectives on the endocrinology of pregnancy.

PMID- 9647575
TI  - Immunolocalization of Le(y) oligosaccharide in endometrium during menstrual cycle
      and effect of early luteal phase mifepristone administration on its expression in
      implantation stage endometrium of the rhesus monkey.
AB  - Changes in carbohydrate expression on endometrial and blastocyst cell surfaces
      may play a critical role in the process of implantation. Le(y) is an
      oligosaccharide antigen which has been shown to be involved in blastocyst
      attachment in the mouse. In the present study, immunohistochemical distribution
      of Le(y) in endometrium during proliferative and secretory phases of normal
      menstrual cycles in the rhesus monkey was examined. Endometrial samples were
      collected on cycle days 7 (n=4), 13 (n= 4), 16 (n=4), 20 (n=4) and 25 (n=3).
      There was a gradual increase of Le(y) in luminal surface from proliferative to
      periovulatory (P < 0.001), and from periovulatory to postovulatory (P < 0.05),
      phases. Le(y) then remained constant in the midsecretory phase and decreased (P <
      0.01) during the premenstrual phase. Le(y) score in glands did not change between
      the phases, except in midsecretory phase when it was higher than that in other
      phases (P < 0.05). The stromal compartment showed no statistically significant
      changes. The profiles of endometrial Le(y) on day 6 after ovulation in mated
      fecund cycles with or without early luteal phase mifepristone treatment were also
      examined. Females were allowed to cohabit with males during days 8-16 of their
      ovulatory cycles and were injected s.c. with vehicle (n=7) only, or with a single
      dose of mifepristone (2 mg/kg body weight; n=8) on day 2 after ovulation.
      Significant decreases in the area and optical absorption of immunoprecipitate
      were observed in the epithelial compartment (P < 0.01) following mifepristone
      treatment. There was no change in the stromal compartment either in area or in
      optical absorption of immunoprecipitate for Le(y) with or without mifepristone
      treatment. The expression of Le(y) in the endometrial epithelial compartment
      appears to be influenced by progesterone and may be associated with endometrial
      receptivity prior to implantation in the rhesus monkey.

PMID- 9647576
TI  - Localization of glutathione S-transferases alpha and pi in human embryonic
      tissues at 8 weeks gestational age.
AB  - Glutathione S-transferases (GST) are a family of enzymes involved in the
      detoxification of xenobiotics. In humans, GST are divided into four different
      classes, alpha, mu, pi and theta, with partly overlapping substrate specificity
      and a tissue-specific expression pattern. We studied the cellular distribution of
      GST alpha and pi in a variety of human embryonic organs obtained from an extra
      uterine monozygotic twin pregnancy at 8 weeks' gestational age. Tissues were
      fixed in 4% paraformaldehyde and embedded in paraffin. Three 4 microm thick
      sections were used, one for routine haematein and eosin staining, the others for
      immunohistochemical determination using monoclonal and polyclonal antibodies
      against GST alpha and pi, respectively. Both GST alpha and pi were present in
      hepatocytes, gastrointestinal epithelium, adrenal gland medulla, and tela
      chorioidea in the telencephalon. GST pi, but not alpha, was found in the
      epithelium of pancreatic and pulmonary glands, trachea, nephrons and urinary
      collecting ducts, as well as in the pia mater of the telencephalon and in
      developing nerve tissue in the gastrointestinal muscularis mucosae. In summary,
      we have demonstrated that immunoreactive protein for both GST alpha and pi is
      expressed in the human embryo at 8 weeks' gestational age. The early expression
      of GST alpha and pi in the epithelia of the urinary and digestive tracts and the
      respiratory system supports the importance of GST in the detoxification of
      potentially toxic or carcinogenic compounds. Our results suggest that the embryo
      itself is capable of detoxifying noxious compounds that are generated
      intracellularly or that cross the trophoblastic tissue.

PMID- 9647577
TI  - Successful pregnancy outcome following Tompkins metroplasty done early in
      pregnancy.
AB  - A hysterosalpingogram revealed a septate uterus in a 29 year old nulliparous
      woman with a history of recurrent pregnancy loss. The patient underwent Tompkins
      metroplasty in the proliferative phase of the menstrual cycle. One month after
      the operation she presented with a delay in her menses and a positive pregnancy
      test. Ultrasound revealed a viable fetus commensurate with 10 weeks gestation,
      making the gestation period 5 weeks at the time of surgery. After reviewing the
      patient's menstrual history it was found that the period the patient had before
      surgery was on time but with unusually minimal bleeding. A repeat ultrasound scan
      for anomaly done 7 weeks later was commensurate with 17 weeks gestation. The
      patient carried her pregnancy for the first time until approximately 37 weeks
      when she delivered by Caesarean section a healthy female baby weighing 3700 g.

PMID- 9647578
TI  - Maternal and fetal insulin-like growth factors and their binding proteins in the
      second and third trimesters of human pregnancy.
AB  - The insulin-like growth factors (IGFs) are mitogenic polypeptides which circulate
      bound to a series of at least six binding proteins (IGFBPs). An increasing body
      of evidence supports a major role for the IGF in the control of human fetal
      growth although normal values in the human fetal circulation have not been
      established. In order to provide an accurate reflection of fetal IGFs and IGFBPs
      in utero, we have sampled fetal blood direct from the umbilical cord at 18-38
      weeks of gestation using the technique of cordocentesis. We have measured IGF-I,
      IGF-II and IGFBP 1-3 in 91 fetuses in order to establish concentrations for these
      parameters in the second and third trimesters of human pregnancy.

PMID- 9647579
TI  - Trends in male:female ratio among newborn infants in 29 countries from five
      continents.
AB  - We have analysed trends in male:female ratios among newborns between 1950 and
      1990 in 29 countries from five continents. The numbers of liveborn males and
      females over the period 1950-1994 were derived from the World Health Organization
      (WHO) database. Countries for which reliable data were available included 20
      major European countries (excluding the former Soviet Union, Albania and a few
      small countries), Canada, the USA, selected countries of Central and South
      America, Japan, Australia and New Zealand. From the original numbers of males and
      females, we computed the proportion of males among liveborns for each country and
      for selected broader areas within Europe. In most countries the proportion of
      male liveborns was constant during the study period. In particular, the
      proportion of male newborns in the European Union was 0.515 in 1950-1954, 0.514
      in 1970-1974 and 0.514 in 1990-1994. In the USA, corresponding values were 0.513,
      0.513 and 0.512. In Japan the ratios were 0.513 in 1950-1954, 0.516 and 1970-1974
      and 0.514 in 1990-1994. Decreasing ratios were observed in some northern and
      eastern European countries plus Greece and Portugal and, particularly, in Mexico.
      In contrast, the proportion of male liveborns tended to increase in southern
      Europe and Australia. Overall, among the 29 countries considered, the proportion
      of males declined in 16, increased in six, and remained stable in seven.

PMID- 9647580
TI  - Sex ratio associated with timing of insemination and length of the follicular
      phase in planned and unplanned pregnancies during use of natural family planning.
AB  - This was a multicentred, prospective study of pregnancies among women using
      natural family planning. The women maintained natural family planning charts of
      the conception cycle, recording acts of intercourse and signs of ovulation
      (cervical mucus changes, including peak day and basal body temperature). Charts
      were used to assess the most probable day of insemination relative to the day of
      ovulation and length of the follicular phase of the cycle. The sex ratio (males
      per 100 females) for 947 singleton births was 101.5, not significantly different
      from the expected value of 105. The sex ratio did not vary consistently or
      significantly with the estimated timing of insemination relative to the day of
      ovulation, with the estimated length of the follicular phase or with the planned
      or unplanned status of the pregnancy. Although these findings may be affected by
      imprecision of the data, the study suggests that manipulation of the timing of
      insemination during the cycle cannot be used to affect the sex of offspring.

PMID- 9647581
TI  - Seasonality of sex ratio in Germany.
AB  - It was investigated whether there is a seasonal variation in sex ratio at birth
      in Germany. The analysis was based on records from the German Bureau for
      Statistics, covering the period from 1946 to 1995. A highly significant (P < or =
      0.001), albeit low-amplitude rhythm was found with two peaks in May and December,
      and two nadirs in March and October. No correlations were found between sex
      ratios and seasonal birth rates during this period.

PMID- 9647582
TI  - Distress level in men undergoing intracytoplasmic sperm injection versus in-vitro
      fertilization.
AB  - The purpose of this study was to compare the psychological reactions of men
      undergoing intracytoplasmic sperm injection (ICSI) (n=18) or in-vitro
      fertilization (IVF) (n=22). Men monitored their psychological reactions daily for
      one complete treatment cycle from the first day of down-regulation until the
      outcome of treatment was known (approximately 52 days). The results showed that
      ICSI patients reported marginally more distress on the days prior to retrieval
      than the IVF patients. Other than this difference the pattern of results
      indicated that the psychological reactions of men undergoing ICSI or IVF were
      similar and that there was no need to manage these patients differently during
      treatment. However, ICSI patients may benefit from some reassuring comments on
      the days prior to retrieval when they showed more anticipatory anxiety.

PMID- 9647583
TI  - The right to an heir in the era of assisted reproduction.
AB  - The latest remarkable technological advances in assisted reproduction, which
      enable cryopreservation of spermatozoa, embryos and ovarian tissue, raise
      difficult and debatable legal, social, ethical and moral issues concerning the
      right to posthumous reproduction. Furthermore, reports on the attitudes of the
      general public and of centres licensed for infertility treatment in the United
      Kingdom found that the majority of women and centres support the idea of
      posthumous reproduction. In this paper we review the data published on this
      issue, and after considering the various aspects, we conclude that each case
      should be discussed and authorized by a multidisciplinary committee that includes
      physicians, clergy, psychiatrists, psychologists, sociologists and other
      appropriate parties. In our opinion, the main principles that should guide this
      committee would allow posthumous reproduction in the context of marriage when a
      prior consent exists. For unmarried persons, post-mortem donation of gametes
      should be done only anonymously, if they are in agreement with existing laws
      concerning infertility treatments in every country and after appropriate consent
      and proper counselling. Moreover, any case which involves consanguinity or a
      possibility of incest should be forbidden, both for ethical and genetic reasons.
      In a case of pre-existing siblings, they should be consulted and their informed
      consent should be granted in advance so as to avoid legal problems in the
      inheritance of property.

PMID- 9647584
TI  - Spontaneous conception in subfertile couples.

PMID- 9647585
TI  - Variation of sex ratio within very large sibships.

PMID- 9647586
TI  - Evaluation of Epstein-Barr Virus infection in hypopharyngeal carcinomas from 37
      Japanese patients.
AB  - Thirty-seven biopsy specimens from primary sites, 18 surgically removed
      metastatic neck nodes, and 18 surgically removed primary sites from 37 patients
      with hypopharyngeal carcinoma (HPC) were evaluated for the presence of Epstein
      Barr Virus (EBV) infection by in situ hybridization (ISH) and polymerase chain
      reaction (PCR). Although some of normal lymphocytes in 6 of 18 metastatic nodes
      were positive by ISH, there were no positive results from HPC tumor cells
      themselves. Our results indicate that EBV-infected non-neoplastic cells such as
      lymphocytes can be a cause of false positivity, if a study were conducted with
      PCR alone. Because ISH for EBV-encoded early RNAs was highly sensitive, even more
      sensitive than PCR from paraffin-embedded samples in our study, this method
      should be the first choice for identification of EBV infection to avoid false
      positives.

PMID- 9647587
TI  - Chronic mucosal changes of the colon in graft-versus-host disease.
AB  - The histologic features of acute graft-versus-host disease (GVHD) of the colon
      are well documented, but chronic mucosal changes associated with GVHD are poorly
      described. We report here the clinicopathologic findings from five patients with
      a history of bone marrow transplantation in which colonoscopic biopsies showed
      chronic mucosal changes reminiscent of chronic idiopathic inflammatory bowel
      disease (IBD). The patients ranged in age from 2.5 to 31 years. Bone marrow
      transplantations were performed for leukemia (3 patients), Hodgkin's disease (1
      patient), and metachromatic leukodystrophy (1 patient). Endoscopy was performed
      because of complaints of abdominal pain and diarrhea in all of the five patients.
      The mean time after transplantation in which histologic features of chronicity
      were identified was 5.8 months (range, 3-16 mo). All of the five patients had
      prior colonic biopsies showing acute GVHD. One patient had a previous episode of
      cytomegalovirus infection. Chronicity was characterized by mild-to-moderate
      architectural distortion, ie., villiform surface with crypt branching and
      atrophy, similar to that seen in chronic idiopathic IBD. The lamina propria was
      hypocellular, with prominent small blood vessels. Focal fibrosis of the lamina
      propria was noted. One patient had active cryptitis. Superimposed changes of
      acute GVHD were mild to absent. None of the patients had a history of IBD before
      receiving the bone marrow transplant. Changes associated with chronicity can be
      observed in mucosal biopsy specimens from patients with GVHD. It is uncertain
      whether these changes are directly caused by GVHD or are the result of
      superimposed infections. The association of chronic mucosal change in the setting
      of GVHD with the clinical diagnosis of chronic GVHD needs additional
      investigation.

PMID- 9647588
TI  - The alpha subunit of inhibin in adrenal cortical neoplasia.
AB  - We analyzed 23 adrenal adenomas and 15 adrenal cortical carcinomas by
      immunolabeling for the alpha subunit of inhibin, and we then compared the results
      with the functional status of the neoplasms. We also studied 19
      pheochromocytomas, 30 renal cell carcinomas, and 5 extra-adrenal paragangliomas,
      tumors posing differential diagnostic problems with adrenal cortical neoplasms.
      Immunolabeling was performed using automated immunohistochemical methods and an
      antibody directed against the alpha subunit. Tumors were semiquantitatively
      assessed for the number of positive cells. Immunopositivity was obtained in 18
      (78%) of 23 adrenal cortical adenomas, 12 (80%) of 15 adrenal cortical
      carcinomas, 2 (11%) of 19 pheochromocytomas, 0 of 5 extra-adrenal paragangliomas,
      and 0 of 30 renal cell carcinomas. Immunoreactivity was strong in 7 (78%) of 9
      adrenal cortical tumors from patients with Cushing's-related or virilizing
      symptoms. In contrast, only 4 (14%) of 29 tumors that were clinically
      nonfunctioning or associated with hyperaldosteronism demonstrated strong staining
      (P < .001). In clinically nonfunctioning tumors, there was a tendency for
      increased immunopositivity in tumors from patients with elevated levels of
      cortisol, androgen, or their precursors, with four of six tumors having at least
      moderate immunopositivity. Similar reactivity was present in only one of eight
      tumors from patients with normal laboratory values (P=.091). Moderate or strong
      immunopositivity was present in 9 (60%) of 15 adrenal cortical carcinomas,
      whereas of the pheochromocytomas, extra-adrenal paragangliomas, and renal cell
      carcinomas, only 1 (1.9%) of 54 showed moderate-to-strong reactivity. We conclude
      that moderate or strong immunoreactivity for the alpha subunit of inhibin occurs
      in adrenal cortical tumors from patients with Cushing's-related or virilizing
      symptoms. Immunolabeling for the inhibin alpha subunit is potentially useful in
      the differential diagnosis of neoplasms that include adrenal cortical carcinomas.

PMID- 9647589
TI  - Multiparametric flow cytometry in the diagnosis and characterization of low-grade
      pulmonary mucosa-associated lymphoid tissue lymphomas.
AB  - Primary mucosa associated lymphoid tissue (MALT) lymphomas are rare neoplasms
      that seem to have a better prognosis than nodal lymphomas. Morphologic diagnosis
      of these lesions may be difficult because of features that overlap with those of
      benign lymphoid infiltrates. In this study, we assessed the contribution of multi
      parametric flow cytometry in demonstrating clonality and further characterizing
      pulmonary MALT lymphomas. Based on a clinical or pathologic suspicion of MALT
      lymphoma, 3 transbronchial biopsies, 4 fine needle aspirates, 1 core needle
      biopsy, and 13 wedge excisions of lung were submitted fresh (unfixed) to our
      laboratory for evaluation. Among the 13 cases diagnosed as MALT lymphomas, B-cell
      monoclonality was established by identifying expression of a single
      immunoglobulin light chain on CD20 or CD19-positive cells in 12 cases. One case
      lacked expression of both light chains on B-cells. Of 11 lymphoma cases in which
      CD5 and CD10 surface antigens were assessed, no cases expressed CD10, and 1 case
      demonstrated weak CD5 expression. Nine of 10 cases studied were diploid and 1
      case was hyperdiploid. All of the lymphomas displayed low (< or = 3%) S-phase
      fractions consistent with low grade processes. In 10 patients with short follow
      up, none died of their disease and the majority had no evidence of lymphoma
      dissemination. In seven of the remaining eight cases, B-cells were polyclonal
      consistent with reactive processes. In one morphologically reactive case, flow
      cytometric analysis was unsuccessful because of poor cell viability. The
      pulmonary MALT lymphomas in this study represent a group of B-cell tumors with
      distinctive morphologic, immunophenotypic, and cell kinetic characteristics.
      Multi-parametric flow cytometry is useful for confirming B-cell monoclonality and
      illustrating an antigenic profile compatible with this diagnosis. Flow cytometry
      can be particularly helpful when working with small biopsies and cytologic
      samples with limited diagnostic material and may abrogate the need for more
      aggressive surgical procedures.

PMID- 9647590
TI  - Expressions of basic fibroblast growth factor and fibroblast growth factor
      receptor mRNA in soft tissue tumors by in situ hybridization.
AB  - Basic fibroblast growth factor (bFGF) is a mitogenic and angiogenic polypeptide
      produced by diverse cell types, including the cells derived from normal tissue
      and neoplastic lesions. To evaluate the possible differential expression of bFGF
      in soft tissue tumors, we examined 17 frozen primary soft tissue tumors including
      extra-abdominal desmoids, leiomyosarcomas, synovial sarcomas, myxoid
      liposarcomas, and alveolar soft part sarcomas by nucleic acid in situ
      hybridization. Three of the four leiomyosarcomas and two of the three synovial
      sarcomas studied expressed bFGF mRNA, whereas all of the myxoid liposarcomas and
      alveolar soft part sarcomas were negative. Two of the leiomyosarcomas were also
      positive for FGF receptor mRNA. These results indicated the possibility of an
      autocrine or paracrine mechanism in the function of bFGF and also lent support to
      the opinion that in situ hybridization is useful for examining cell character.

PMID- 9647591
TI  - Neuroendocrine neoplasms arising in inflammatory bowel disease: a report of 14
      cases.
AB  - Inflammatory bowel disease (IBD), particularly ulcerative colitis (UC), is a
      premalignant condition, because these patients are at increased risk of
      adenocarcinoma. Neuroendocrine neoplasms (NENs) have rarely been described in
      this setting. We evaluated 14 cases of NEN arising in a setting of IBD. All of
      the tumors arose in areas involved by IBD, and all showed immunohistochemical or
      ultrastructural evidence of neuroendocrine differentiation. The cohort included
      seven men and seven women (range, 28-71 yr; median, 43 yr). Eight patients had
      Crohn's disease (CD), and six had UC. Duration of disease ranged from 4 months to
      50 years (median, 15 yr), with one of unknown duration. Of the eight patients
      with CD, five had ileocolitis, one had ileitis, one had colitis, and in one case,
      the extent of disease was unknown. Of the six patients with UC, four had
      extensive UC, one had left-sided UC, and the extent of UC was unknown in one
      case. Reasons for surgery included CD complications (five patients), refractory
      disease (three patients), dysplasia/carcinoma (five patients), and incontinence
      (one patient). The NENs were well differentiated in 11 cases and poorly
      differentiated mixed adenocarcinoma/small cell carcinomas in 3 cases. Tumor sites
      included the rectum (six cases), appendix (four cases), small bowel (two cases),
      and sigmoid colon (two cases). High-grade dysplasia was present in adjacent
      mucosa in four cases, and low-grade dysplasia was present in distant mucosa in
      two cases. Two patients with poorly differentiated NENs died from the disease at
      3 and 11 months after tumor excision. All of the other patients were alive
      without tumor as of last follow-up. We concluded that NENs rarely arise in a
      setting of IBD. Most are well-differentiated tumors and are clinically indolent.
      Dysplasia is found in adjacent mucosa in more than one-third of cases, suggesting
      that neuroendocrine differentiation might evolve from multipotential cells in
      dysplastic epithelium.

PMID- 9647592
TI  - Minimal carcinoma in prostate needle biopsy specimens: diagnostic features and
      radical prostatectomy follow-up.
AB  - Prostate cancer screening and early detection efforts have resulted in the
      identification of smaller volume carcinomas of the prostate. We evaluated the
      diagnostic features of minimal (< 1 mm) carcinoma in sextant needle biopsy
      specimens of the prostate and in follow-up analyzed the features of the
      corresponding carcinomas in the whole gland. We reviewed specimens from 50
      consecutive patients who had minimal carcinoma in needle biopsy tissue and who
      had undergone radical prostatectomy. Histologic grade, tumor size, pathologic
      stage, and margin status of the 50 carcinomas in the whole gland in which the
      carcinoma size was minimal in the sextant needle biopsy specimen were compared
      with those of 50 carcinomas in the whole gland in which carcinoma size was
      greater than 1 mm in the needle biopsy specimen. The most common morphologic
      features of these minimal carcinomas were nucleomegaly (96%), infiltrative growth
      pattern (88%), intraluminal secretions (78%), prominent nucleoli (64%),
      associated high-grade prostatic intraepithelial neoplasia (40%), amphophilic
      cytoplasm (36%), hyperchromatic nuclei (30%), and intraluminal crystalloids
      (22%). Perineural invasion (2%), collagenous micronodules (2%) and mitotic
      figures (2%) were uncommon. The mean tumor volume in the whole gland of
      carcinomas corresponding to minimal carcinoma in a needle biopsy specimen was
      significantly smaller (P=.029) at 1.1 mL than it was in carcinomas with tumor
      greater than 1 mm in the needle biopsy specimen at 1.6 mL, but other pathologic
      features of carcinoma in the whole gland were not significantly different. In
      conclusion, a constellation of morphologic attributes is important for
      establishment of a diagnosis of minimal carcinoma of the prostate in needle
      biopsy specimen. Most (82%) of the corresponding prostate cancers in the whole
      gland were pathologically significant.

PMID- 9647593
TI  - Prostatic carcinoma with signet ring cells: a clinicopathologic and
      immunohistochemical analysis of 12 cases, with review of the literature.
AB  - Prostatic adenocarcinoma with a signet ring cell (SRC) component is a rare,
      incompletely characterized variant that must be distinguished from similar tumors
      of bladder or gastric origin. In this study, we used mucin and immunoperoxidase
      stains on formalin-fixed, paraffin-embedded sections from 12 prostatic
      adenocarcinomas with SRC components, with antibodies to prostate-specific antigen
      (PSA), cytokeratins, MIB-1, bcl-2, c-MET, CD44v6, and CD44v7; we performed a
      comparison study on six bladder and seven gastric carcinomas with SRCs. The
      prostatic SRC component was always associated with the usual high-grade
      adenocarcinoma. Both components were positive for PSA, AE1/AE3, and CAM 5.2 (12
      cases of 12) and also expressed c-MET (5 cases of 9), CD44v6 (9 of 10), and CDv7
      (9 of 10). Only rare cells stained for bcl-2 (3 cases of 9). The mean MIB-1
      proliferation index was 8%. Intracellular mucin was identified (periodic acid
      Schiff with diastase predigestion (PAS-D) in 9 cases of 10, mucicarmine in 5 of
      10, alcian blue in 6 of 10). Bladder and gastric tumors were positive for PSA (3
      cases of 6 and 2 of 7, respectively), using a polyclonal antibody, and for bcl-2
      (5 cases of 6, 2 of 7), c-MET (6 of 6, 6 of 7), CD44v6 (5 of 6, 6 of 7), and
      CD44v7 (4 of 6, 4 of 7), with mean MIB-1 proliferation indices of 15 and 35%,
      respectively. All were negative for cytokeratin 34 beta E12. We conclude that
      prostatic adenocarcinomas with SRC components are typically accompanied by high
      grade adenocarcinoma; are variably positive for mucin, with PAS-D being the most
      sensitive stain; show expression of PSA, cytokeratins, MIB-1, bcl-2, c-MET, and
      CD44 similar to that shown by high-grade adenocarcinoma components; have a low
      MIB-1 proliferation index; and are not always distinguishable from SRC components
      of bladder and stomach carcinomas with any of the above stains, including PSA.

PMID- 9647594
TI  - Nonalcoholic fatty liver disease: assessment of variability in pathologic
      interpretations.
AB  - The exact cause, prevalence, and rate of progression of nonalcoholic fatty liver
      disease (NAFLD) are unclear because of a lack of agreement on the pathologic
      features associated with the different types of NAFLD, their clinical syndromes,
      and because of a lack of accuracy in the interpretation of these pathologic
      features. Studies of NAFLD would be aided by a consistent and standardized
      approach to the interpretation of pathologic features. The aim of our study was
      to assess interobserver and intraobserver variation in the histologic
      abnormalities associated with NAFLD. We identified histologic features of NAFLD
      as reported in the literature, and we identified patients with the diagnosis of
      NAFLD through the databases of two large institutions. Histologic parameters were
      evaluated for each liver biopsy specimen by four hepatopathologists and twice by
      two of the four pathologists (blindly). Interobserver and intraobserver
      concordance among the pathologists was measured by kappa statistics. Nineteen
      histologic parameters compartmentalized into steatosis, inflammation, liver cell
      injury, and fibrosis were evaluated on 53 liver biopsy specimens. Significant,
      substantial, or moderate concordance was present in only six items: the extent of
      steatosis, sinusoidal location of fibrosis, perivenular fibrosis, grade of
      fibrosis, ballooning degeneration, and the presence of vacuolated nuclei.
      Substantial or moderate concordance also was seen for interobserver readings for
      location of steatosis and periportal injury. Parameters of inflammation were not
      scored as reliably as parameters of fibrosis and cell injury. We conclude that
      only some histologic features previously reported in NAFLD (especially those with
      substantial and moderate concordance for both interobserver and intraobserver
      interpretation) are interpreted uniformly by experienced pathologists. These
      histologic features might prove useful for the development of a standardized and
      reliable pathologic scoring system that includes the full histologic spectrum of
      NAFLD and its various clinical outcomes.

PMID- 9647595
TI  - Peripheral pulmonary adenocarcinomas with bronchioloalveolar features:
      immunophenotypes correlate with histologic patterns.
AB  - Peripheral pulmonary adenocarcinomas (PPAs) often demonstrate a
      bronchioloalveolar component, with or without glandular differentiation. PPAs can
      be nondescript, mucinous, or show features of Type II pneumocytes. Particularly,
      mucinous lung carcinomas can resemble gastrointestinal metastases. Previous
      reports suggested that patterns of keratins 7 (K7) and 20 (K20) differ in
      pulmonary tumors versus enteric metastases. These studies, however, often failed
      to specify the precise morphotypes of PPA. Thus, we undertook this evaluation of
      PPAs with different histologic images. Thirty-nine cases were retrieved from
      institutional files; all were confirmed as primary tumors by clinicopathologic
      and radiographic review. Cases were classified as Type I (mucinous)
      bronchioloalveolar carcinoma (BAC1); Type II (nonmucinous) bronchioloalveolar
      carcinoma (BAC2); conventional PPA with BAC1-like areas (PPA1); or conventional
      PPA with BAC2-like foci (PPA2). Immunostains were performed for K7, K20,
      carcinoembryonic antigen, CA19-9, tumor-associated glycoprotein-72, surfactant
      apoprotein-A, and the c-erbB-2 peptide. BAC1 and PPA1 failed to express
      surfactant apoprotein-A, and BAC2 also consistently lacked K20, whereas 28% of
      PPA2 lesions were labeled for K20. All of the other determinants, however, were
      seen in variable proportions in each subgroup of PPA. Primary BAC1 and PPA1
      resembled enteric adenocarcinomas immunophenotypically; on the other hand, BAC2
      demonstrated a pattern of protein expression similar to that of Type II
      pneumocytes. PPA2s are a diverse group of neoplasms, and a subset of PPA2 does
      show K20 reactivity, as would be expected in metastatic enteric carcinomas. Thus,
      immunohistochemical data on PPAs must be interpreted carefully and only in
      clinicopathologic context. With respect specifically to primary pulmonary
      mucinous tumors, there still seems to be no uniformly reliably marker that will
      always allow the exclusion of metastatic enteric tumors.

PMID- 9647596
TI  - Neurocristic cutaneous hamartoma: a distinctive dermal melanocytosis with an
      unknown malignant potential.
AB  - Neurocristic hamartomas (NCHs) result from aberrant development of the
      neuromesenchyme. In addition to a dermal melanocytic component, these tumors can
      contain neurosustentacular and fibrogenic components and can undergo malignant
      transformation. Although NCHs have many features in common with other dermal
      melanocytic neoplasms, including cellular blue nevi and some congenital nevi,
      they have distinctive clinical and histologic features. We present a case report
      of a 27-year-old white woman with an NCH of the scalp. The clinical, histologic,
      and immunohistochemical features are compared with those of other dermal
      melanocytic neoplasms. The NCH contained epithelioid pigmented melanocytes
      positive for S-100 and HMB45, within which there were well-circumscribed nodules
      of S-100+/Leu 7+/HMB45- cells surrounded by a capsule composed of spindle cells
      positive for epithelial membrane antigen. The stromal cells throughout the tumor
      were diffusely CD34 positive, and hair follicles were decreased and dystrophic
      within the tumor. NCHs represent neoplastic dysplasia that involves not only
      melanocytic cells but also neurosustentacular and fibrocytic effector cells. The
      histologic and immunohistochemical features, along with the decreased and
      dystrophic hair follicles, suggest that the abnormalities in the mesenchyme are
      significant and result from the contribution of neural crest cells to the
      cellular and matrix components of the mesenchyme.

PMID- 9647597
TI  - Primary fibrosarcoma of the sella unrelated to previous radiation therapy.
AB  - Fibrosarcomas involving the sella turcica are rare lesions and, when encountered,
      have been associated with previous radiation of a pituitary adenoma. Although
      primary intracranial fibrosarcomas are well recognized, no case of primary
      fibrosarcoma of the sella turcica has been reported to date. We describe here a
      patient who presented with a 2-month history of headache, visual disturbances,
      and diabetes insipidus. Her past medical history was unremarkable, with no
      radiation therapy. Magnetic resonance imaging revealed a sellar/suprasellar
      lesion that at surgery appeared firm in consistency. A radical removal of the
      mass was performed through a transsphenoidal approach. The patient recovered
      promptly from the operation and 2 weeks later, given the aggressive histologic
      appearance of the lesion, underwent gamma knife radiosurgery. Seven months after
      diagnosis, the patient presented with local tumor recurrence. A subtotal surgical
      resection was performed, and additional postsurgical treatment is still under
      consideration. Although most often related to previous radiation of the pituitary
      gland, primary fibrosarcomas can occur in the sella. This possibility should be
      suspected in the differential diagnosis of sellar masses that lack the classical
      characteristics of the much more common pituitary adenomas.

PMID- 9647598
TI  - "Directoring" and managing in a professional system.
AB  - Pathologists are under siege by corporate medicine, managed care systems, or
      varieties of government-initiated health care restructuring. The pressure is on
      us to attend at least equally to fiscal pressures, as well as to our patients'
      medical needs. These pressures must be accommodated within the limits of our
      professional duties and responsibilities. We must have more than an intuitive
      sense of what it is to be a professional and to work in a system that is overseen
      typically by a directorate and that includes managers and innovators. The example
      of the failure of the corporate managers and directors of a national blood
      transfusion service highlights the need to balance the inter-relationships of
      managers, professionals, and innovators by a directorate knowledgeable in these
      complex systems.

PMID- 9647599
TI  - Correspondence re: Casey M, Rosenblatt R, Zimmerman J, Fineberg S. Mastectomy
      without malignancy after carcinoma diagnosed by large-core stereotactic breast
      biopsy. Mod Pathol 1997;10:1209-13.

PMID- 9647600
TI  - Correspondence re: Sano T, Hikino T, Niwa Y, Kashiwabara K, Oyama T, Fukuda T,
      Nakajima T. In situ hybridization with biotinylated tyramide amplification:
      detection of human papillomavirus DNA in cervical neoplastic lesions. Mod Pathol
      1998;11:19-23.

PMID- 9647601
TI  - Leukotrienes and inflammation.
AB  - Leukotrienes are potent pro-inflammatory mediators that appear to contribute to
      pathophysiologic features of asthma. For example, cysteinyl leukotrienes contract
      airway smooth muscle, increase microvascular permeability, stimulate mucus
      secretion, decrease mucociliary clearance, and appear capable of recruiting
      eosinophils into the airways. Segmental antigen bronchoprovocation in patients
      with asthma increases LTC4 concentrations in bronchoalveolar lavage fluid, which
      correlates with an influx of eosinophils into the airways. LTB4, in comparison,
      selectively affects neutrophil functions. Intratracheal instillation of LTB4
      produced a selective recruitment of neutrophils into the lung. These effects
      suggest that leukotrienes contribute significantly to the inflammatory components
      of asthma.

PMID- 9647602
TI  - Pharmacology of leukotriene receptor antagonists.
AB  - Preclinical pharmacological studies have demonstrated that cysLT, receptor
      antagonists, such as zafirlukast, montelukast, and pobilukast, are potent and
      selective antagonists of cysteinyl leukotriene (cysLT) activity. In vitro, these
      agents compete with [3H]LTD4 for binding to cysLT, receptors present on guinea
      pig and human lung cell membranes. Both zafirlukast and montelukast have
      affinities that are approximately two times greater than that of the natural
      ligand, LTD4. These agents block LTD4- and LTE4-induced contractions of isolated
      guinea pig trachea, but do not antagonize LTC4-induced contractions, which are
      putatively mediated by a different LT receptor, cysLT2. The cysLT2 receptor,
      however, has not yet been found in human airway smooth muscle. In animal models,
      these drugs inhibit LTD4-, LTE4-, and antigen-induced bronchoconstriction, reduce
      inflammatory markers in models of pulmonary inflammation, and inhibit antigen
      induced late-phase bronchoconstriction. This preclinical profile suggests that
      cysLT, receptor antagonists may be useful in treating inflammatory conditions of
      the respiratory system, such as asthma and allergic rhinitis.

PMID- 9647603
TI  - Chemistry and structure--activity relationships of leukotriene receptor
      antagonists.
AB  - Several strategies have been employed by medicinal chemists in the design of
      potent and selective leukotriene receptor antagonists-leukotriene structural
      analogs, FPL 55712 analogs, and random screening of corporate compound banks.
      Lead compounds were optimized, often through the exchange of ideas with groups
      working on other chemical series of leukotriene antagonists. Pranlukast can
      likely be traced to a lead compound identified by random screening that was
      initially modified by incorporating structural components present in FPL 55712.
      Montelukast originated from an early quinoline lead, which was modified with
      leukotriene structural elements. Zafirlukast is based on a lead compound that
      incorporated structural components from both FPL 55712 and the leukotrienes.
      Therefore, each medicinal chemistry strategy that was originally employed has
      successfully identified clinically effective leukotriene receptor antagonists.

PMID- 9647604
TI  - Cell biology of the 5-lipoxygenase pathway.
AB  - The initial enzymatic steps in leukotriene synthesis occur at the nuclear
      envelope. Cytosolic phospholipase A2 translocates from the cytoplasm to
      selectively hydrolyze nuclear envelope phospholipids, releasing free
      arachidonate. 5-Lipoxygenase-activating protein, an arachidonate transfer
      protein, then binds arachidonate and presents it to 5-lipoxygenase (5-LO), which
      catalyzes a two-step reaction to produce leukotriene A4. In resting human and rat
      peripheral blood neutrophils, 5-LO is localized to the cytoplasm; in rat
      basophilic leukemia cells and human alveolar macrophages, however, it is found
      predominantly in the nucleus. Immunofluorescence microscopy studies demonstrate
      that both cytoplasmic and nuclear 5-LO move to the nuclear envelope following
      cell activation. Many questions remain unanswered regarding the significance of
      nuclear 5-LO, potential autocrine actions of leukotrienes, and intracellular
      trafficking of these enzymes and their products.

PMID- 9647605
TI  - Clinical pharmacology of leukotriene receptor antagonists and 5-lipoxygenase
      inhibitors.
AB  - Blinded, randomized, and placebo-controlled clinical trials have established that
      cysteinyl leukotriene (cysLT) receptor antagonists and 5-lipoxygenase (5-LO)
      inhibitors are safe and effective asthma treatments. Trials of 13- to 26-wks'
      duration demonstrate that both the cysLT1 receptor antagonist, zafirlukast, and
      the 5-LO inhibitor, zileuton, improve pulmonary function and decrease daytime and
      nocturnal symptoms. Concomitant rescue beta-agonist inhaler use and the need for
      corticosteroid rescue are also reduced. Preliminary studies suggest that
      antileukotriene agents may also reduce indices of airway inflammation, including
      inflammatory cell counts and airway hyperresponsiveness. Both cysLT1 antagonists
      and 5-LO inhibitors offer a new approach to asthma management.

PMID- 9647606
TI  - Summary of clinical trials with zafirlukast.
AB  - Zafirlukast is an orally active and selective cysteinyl leukotriene (cysLT)
      receptor antagonist. In humans, zafirlukast antagonized the effects of
      exogenously administered LTD4 and cysLTs released endogenously in response to
      physical and chemical stimuli. Zafirlukast antagonized LTD4-induced
      bronchoconstriction, with effects still evident 12 h after drug administration.
      In clinical models of asthma, zafirlukast inhibited bronchospasm after allergen
      or exercise challenge in patients with asthma. In multicenter trials in patients
      with chronic, stable asthma, zafirlukast reduced asthma symptoms, decreased as
      needed beta-agonist use, and improved pulmonary function without increasing the
      number of adverse events. Zafirlukast also exhibited evidence of an anti
      inflammatory effect in the lung in preliminary studies involving segmental
      antigen challenge. The results from these clinical trials demonstrate that
      zafirlukast is effective and safe for the prophylactic treatment of asthma.

PMID- 9647607
TI  - Basic and clinical aspects of myocardial stunning.
AB  - Although the pathogenesis of myocardial stunning has not been definitively
      established, the two major hypotheses are that it is caused by the generation of
      oxygen-derived free radicals on reperfusion and by a loss of sensitivity of
      contractile filaments to calcium. These hypotheses are not mutually exclusive and
      are likely to represent different facets of the same pathophysiological cascade.
      For example, a burst of free radical generation after reperfusion could alter
      contractile filaments in a manner that renders them less responsive to calcium.
      Increased free radical formation could also cause cellular calcium overload,
      which would damage the contractile apparatus of the myocytes. There is now
      considerable evidence that myocardial stunning occurs clinically in various
      situations in which the heart is exposed to transient ischemia, such as unstable
      angina, acute myocardial infarction with early reperfusion, exercise-induced
      ischemia, cardiac surgery, and cardiac transplantation. Recognition of myocardial
      stunning is clinically important and may impact patient treatment. Although no
      ideal diagnostic technique for myocardial stunning has yet been developed,
      thallium-201 scintigraphy or dobutamine echocardiography are available and can be
      useful to identify viable myocardium with reversible wall motion abnormalities.
      An intriguing possibility is that so-called chronic hibernation may in fact be
      the result of repetitive episodes of stunning, which have a cumulative effect and
      cause protracted postischemic left ventricular dysfunction. A better
      understanding of myocardial stunning will expand our knowledge of the
      pathophysiology of myocardial ischemia and provide a rationale for developing new
      therapeutic strategies designed to prevent postischemic dysfunction.

PMID- 9647608
TI  - Ischemic preconditioning: exploring the paradox.
AB  - Brief transient episodes of nonlethal myocardial ischemia protect or
      "precondition" the heart and render the myocardium resistant to a subsequent more
      sustained ischemic insult. The hallmark of this phenomenon--documented in
      virtually all species and experimental models evaluated to date in countless
      laboratories worldwide--is the profound reduction in infarct size seen in
      preconditioned groups versus time-matched controls. Efforts to identify the
      cellular mechanisms responsible for this paradoxical ischemia-induced
      cardioprotection, to expand the definition of ischemic preconditioning beyond
      infarct size reduction, and, perhaps most importantly, to evaluate the efficacy
      of preconditioning in disease models and in the clinical setting, are all topics
      of intensive ongoing investigation.

PMID- 9647609
TI  - Apoptosis in heart failure.
AB  - A characteristic feature of heart failure is the progressive worsening of
      ventricular function over months or years despite the absence of clinically
      apparent intercurrent adverse events. The mechanism or mechanisms responsible for
      this hemodynamic deterioration are not known but may be related to progressive
      intrinsic contractile dysfunction of residual viable cardiac myocytes, or to
      ongoing degeneration and loss of myocytes, or both. This report will address the
      concept of ongoing cardiac myocyte loss that may occur during the course of
      evolving heart failure viewed from the perspective of apoptosis or "programmed
      cell death" as the potential mediator of cardiac muscle cell loss. In recent
      years, several studies have shown that constituent myocytes of failed explanted
      human hearts and hearts of animals with experimentally induced heart failure
      undergo apoptosis. Recent studies have shown that cardiac myocyte apoptosis also
      occurs after acute myocardial infarction, as well as in the hypertrophied heart
      and the aging heart, conditions frequently associated with the development of
      heart failure. Considerable work has also been conducted and novel concepts
      advanced to explain potential molecular triggers of cardiac myocyte apoptosis in
      heart failure. Although available data support the existence of myocyte apoptosis
      in the failing heart, questions essential to our understanding of the importance
      of myocyte apoptosis in this disease process remain unanswered. Lacking are
      studies aimed at identifying physiological factors inherent to heart failure that
      trigger myocyte apoptosis. Also lacking are studies that address the importance
      of myocyte apoptosis in the progression of left ventricular dysfunction. If loss
      of cardiac myocytes through apoptosis can be shown to be an important contributor
      to the progression of heart failure, and if factors that trigger apoptosis in the
      heart can be identified, such knowledge can potentially lead to the development
      of novel therapeutic modalities aimed at preventing, or at the very least
      retarding, the process of progressive ventricular dysfunction and the ultimate
      transition toward end-stage, intractable heart failure.

PMID- 9647610
TI  - Aortic pain.
AB  - With the exception of the pain of acute aortic dissection, the thoracic aorta is
      not usually considered as a pain-producing organ. However, nineteenth century
      clinicians considered the aorta as a source of cardiovascular pain in the
      presence of autopsy-documented inflammatory aortitis, aortic aneurysms, and
      arterial hypertension, whereas early in the twentieth century, aortic pain
      reactions were elicited in experimental studies involving distension of the
      ascending aorta or the application of stimulating substances to the outer surface
      of the aorta. More recently, increased attention to aortic elastic properties,
      and to aortic vascular biology at the molecular level refocused interest on the
      many facets of aortic function beyond that of a simple conduit. The recognition
      of pain of thoracic aortic origin now extends to patients with progressive aortic
      syndromes such as aortic intramural hematoma, aortic intimal tears, aortic
      penetrating ulcers, aortic root dilatation without dissection in connective
      tissue disorders, inflammatory aortopathies, and abnormalities of aortic
      distensibility. The occurrence of pain during balloon inflation at balloon
      angioplasty of aortic coarctation, which disappears immediately after deflation,
      is the modern equivalent of the early experimental studies. The authors present a
      consideration of thoracic aortic pain in light of contemporary concepts in
      cardiovascular medicine with roots in the rich historical reservoir of
      information about aortic function and disease.

PMID- 9647611
TI  - Oxaliplatin (L-OHP): a new reality in colorectal cancer.
AB  - Oxaliplatin (trans-/-diaminocyclohexane oxalatoplatinum; L-OHP) is a new platinum
      derivative for the treatment of advanced colorectal cancer. Preclinical data have
      shown that oxaliplatin is active in a wide range of human and murine tumour cell
      lines, and has been found to be non-cross-resistant with cisplatin in various
      cisplatin-resistant cell lines and tumours. Oxaliplatin in combination with 5
      fluorouracil (5-FU) leads to synergistic antiproliferative activity both in vivo
      and in vitro. Clinical data have shown that oxaliplatin is active and well
      tolerated both as monotherapy and in combination with 5-FU/folinic acid in first-
      or second-line treatment of patients with metastatic colorectal cancer.
      Oxaliplatin has a very good safety profile, and studies have confirmed that
      peripheral sensory neuropathy is related to the cumulative dose of oxaliplatin
      administered and that this neuropathy is generally reversible after
      discontinuation of treatment. High response rates and prolonged survival have
      been achieved in metastatic colorectal cancer patients, even after 5-FU failure.

PMID- 9647612
TI  - Oxaliplatin in practice.
AB  - Oxaliplatin, a new third-generation platinum complex, is active in the treatment
      of colorectal and advanced ovarian cancers, both as monotherapy and in
      combination therapy. It has demonstrated a very good safety profile,
      characterized by low haematotoxicity, and moderate and manageable
      gastrointestinal toxicity. No significant renal or ototoxicities have been
      observed. Oxaliplatin induces a peripheral sensory neuropathy which is
      characterized by distal and perioral dysaesthesia, and is induced or exacerbated
      by the cold; in general, it is regressive between cycles of treatment. This dose
      limiting toxicity is cumulative, but reversible within a few months of
      discontinuation of treatment in the majority of cases. In a cohort study of 490
      patients with advanced colorectal cancer included in an extended access
      programme, more than 2700 cycles of oxaliplatin plus 5-fluorouracil (5-FU) were
      administered. The overall safety profile of oxaliplatin was shown to be very
      favourable. Oxaliplatin and cisplatin, each in combination with cyclophosphamide,
      have a similar efficacy in the treatment of advanced ovarian cancer, but
      oxaliplatin was better tolerated than cisplatin in terms of haematological,
      gastrointestinal, neurosensory and renal toxicities. The safety profile of
      oxaliplatin makes it an ideal candidate for combination therapy.

PMID- 9647613
TI  - Ongoing and unsaid on oxaliplatin: the hope.
AB  - Oxaliplatin, the first available diaminocyclohexane platinum, has clinical
      activity in colorectal and ovarian cancers. Its mechanism of action is thought to
      be similar to that of cisplatin, its main mechanism being the intrastrand DNA
      adduct between two adjacent guanins or two adjacent guanine and adenine adducts.
      Ongoing molecular pharmacological studies of the mechanism of action of cisplatin
      suggest that platinated adducts are recognized by proteins of the mismatch repair
      system, including the products of the hMLH1 and hMSH2 genes. DNA mismatch repair
      defects occur in a wide variety of sporadic human cancers, are the main genetic
      factor in hereditary non-polyposis colon cancer and a frequent de novo or
      acquired phenomenon in ovarian cancer and other solid tumours. Moreover, they
      have recently been reported to be a cause of resistance to cisplatin but not to
      oxaliplatin, as diaminocyclohexane platinum adducts do not appear to be
      recognized by the mismatch repair complex. These findings explain the oxaliplatin
      activity in some cisplatin-resistant tumours. In addition, the good safety
      profile of oxaliplatin makes it a drug of choice for combination therapy, and it
      has been shown to be synergistic with other cytotoxic agents, including 5
      fluorouracil, cisplatin, carboplatin, topotecan, gemcitabine and CPT-11. The
      results of several ongoing trials are awaited, but available data demonstrate
      that oxaliplatin is highly effective in the treatment of advanced colorectal and
      ovarian cancers. Promising early results suggest that it is also efficacious in
      non-Hodgkin's lymphoma, breast and non-small-cell lung cancers. As a result of
      its mechanism of action, its favourable safety profile and the differential
      profile of its antitumoral activity, the full potential of oxaliplatin as an
      active, versatile antitumoral agent is yet to be fully explored.

PMID- 9647614
TI  - Exploiting tumour hypoxia and overcoming mutant p53 with tirapazamine.
AB  - Human solid tumours are composed of a significant proportion of hypoxic cells,
      i.e. cells with oxygen levels lower than those of normal tissues. Tumour hypoxic
      cells have been shown to have a negative impact on the response of solid tumours
      to radiation therapy and chemotherapy. However, these low cellular oxygen levels
      can be exploited by a drug that is specifically activated to a cytotoxic
      metabolite at these low levels. Tirapazamine is a novel bioreductive agent with
      selective cytotoxicity to hypoxic tumour cells, irrespective of their p53 status
      or apoptotic response, and acts synergistically with cisplatin. This potentiation
      is dependent on an interaction that can only take place in a hypoxic environment,
      resulting in a significant sensitization of the cells to cisplatin cell killing,
      with no increase in the systemic toxicity of cisplatin. Thus, the low cellular
      oxygen levels common in solid tumours can be turned from disadvantage to
      advantage using the hypoxia-selective cytotoxic drug tirapazamine.

PMID- 9647615
TI  - Tirapazamine-cisplatin: the synergy.
AB  - Tirapazamine is a novel bioreductive agent with selective cytotoxicity against
      hypoxic tumour cells. Synergy with cisplatin and other chemotherapeutic agents
      has been shown in preclinical trials. Pharmacokinetic studies of tirapazamine
      have revealed that exposure increases with dose over the range of 18-450 mg m(-2)
      for a single dose and of 9-390 mg m(-2) for multiple doses. Plasma clearance is
      high. Tirapazamine has been clinically tested in combination with cisplatin at
      escalating doses in a phase I trial and at therapeutic doses in three separate
      phase II trials in patients with advanced non-small-cell lung cancer (NSCLC) in
      11 study centres. Limiting toxicity for tirapazamine at an intravenous dose of
      390 mg m(-2) was acute, reversible hearing loss. Other frequently observed side
      effects included muscle cramping and gastrointestinal symptoms. Tirapazamine did
      not cause myelosuppression, and no toxic deaths were reported in these trials.
      The anti-tumour efficacy against previously untreated, advanced NSCLC was
      evaluated by cumulative intent-to-treat analysis of 132 patients. The objective
      response rate (confirmed by two independent measurements) was 25% [confidence
      interval (CI) 17.8-33.33], with a median survival of 38.9 weeks (CI 29.4-49.9).
      The efficacy of tirapazamine plus cisplatin shown in these trials was better than
      that of historical controls with cisplatin monotherapy. Two large-scale
      international trials have been conducted, involving more than 70 centres, to
      confirm these results. The CATAPULT I trial compares tirapazamine plus cisplatin
      with cisplatin and has finished accrual with 446 patients. The CATAPULT II trial,
      which is comparing tirapazamine plus cisplatin with etoposide plus cisplatin, had
      enrolled 550 patients by June 1997. Follow-up is ongoing. Tirapazamine is the
      promising first drug from a new class of cytotoxic agents with a novel mechanism
      of action. It can be effectively combined with cisplatin, and possibly with other
      agents, because of its safety profile and lack of overlapping dose-limiting
      toxicity, such as myelosuppression. The combination of tirapazamine and cisplatin
      appears to be safe and effective in the treatment of NSCLC.

PMID- 9647616
TI  - Advances in the management of malignancy-associated hyperuricaemia.
AB  - Acute tumour lysis syndrome (ATLS) is a metabolic derangement (hyperuricaemia,
      hyperphosphataemia, hyperkalaemia and hypocalcaemia) associated with
      lymphoproliferative malignancies. The nature and severity of the metabolic
      alterations are variable. Major complications are oliguric acute renal failure
      and delays in initiating chemotherapy. Current management of ATLS includes
      hydration, alkalinization, diuretics, when indicated, and the reduction of uric
      acid levels using allopurinol or urate oxidase. Allopurinol inhibits xanthine
      oxidase, an enzyme that catalyses the conversion of hypoxanthine and xanthine to
      uric acid. Urate oxidase (Uricozyme), a naturally occurring proteolytic enzyme in
      many mammals, degrades uric acid to allantoins, which are ten times more soluble
      than uric acid and easily eliminated by the kidneys. Recently, Sanofi Research
      isolated a recombinant urate oxidase (SR29142) as a cDNA clone from Aspergillus
      flavus, expressed in the yeast strain Saccharomyces cerevisiae. Preclinical
      studies have documented its biological effects as a urolytic enzyme. Twenty-eight
      healthy male volunteers received SR29142, and a rapid decline of uric acid below
      measurable levels was seen within 4 h in all patients receiving a dose of more
      than 0.10 mg kg(-1). Currently, SR29142 is undergoing clinical studies in both
      Europe and the USA in patients with acute leukaemias or B-cell non-Hodgkin's
      lymphoma to demonstrate its efficacy and safety in this population of patients at
      highest risk of developing ATLS or its life-threatening sequelae.

PMID- 9647617
TI  - [Experimental study on direct volume reconstruction].
AB  - Application of DVR is investigated with the X-ray equipment under single circle
      imaging geometry. A real volume model that consists of aluminum bar, lucite and
      air bar is designed. A prototype imaging system that includes X-ray cone-beams
      ource, rotating system, fluorescent screen, image intensifier, TV camera, image
      acquisitor and microcomputer is constructed. The experimental results show that
      DVR with the current simple X-ray equipment is of interests and values.

PMID- 9647618
TI  - [The design of an OEM module-based hand-hold pulse oximeter].
AB  - This paper describes the software and hardware design of an OEM module-based hand
      hold pulse oximeter. The instrument has the features of compact structure,
      reliable performance, having all the necessary functions, providing measurements
      on any patients and low power consumption. It is possible to make this instrument
      as a commercial product in shorter period.

PMID- 9647619
TI  - [The development of a laser back-scattering erythrocyte-aggregometer].
AB  - In this paper, an erythrocyte-aggregometer based on the analysis of the light
      intensity back-scattered by a blood suspension is presented and described in
      detail. It allows to approach aggregation phenomenon in terms of kinetics,
      structural and rheological parameters. A personal computer and a microcomputer
      are applied to automate the system's sampling, data-processing and data-restoring
      procedure.

PMID- 9647620
TI  - [A CR-self-adjusting data compression algorithm based on complex Fourier
      transform].
AB  - A CR-self-adjusting data compression algorithm based on complex Fourier transform
      is presented in this paper. Because of the application of CFFT algorithm, the CR
      is doulbled with high fidelity without the operations of QRS complex detection,
      wave form analysis and difference calculation.

PMID- 9647621
TI  - [The microcomputer controlling system of rotating gamma ray knife].

PMID- 9647622
TI  - [A technique of PVC detection in QRS wave].
AB  - A technique of PVC detection is described in this paper. The procedures of PVC
      analysis include noise detection, QRS detection, feature extraction and QRS wave
      classification. The interference is detected in hierarchy ways. A new non-linear
      transformation of ECG waveform is given to be taken as the QRS detection
      function. Taking this QRS detection function, the influence of noise and
      interference can be reduced greatly. By the technique of QRS template matching,
      QRS waveforms are sorted into different clusters in QRS wave form space. Then a
      linear classifier is used to identify the medical meaning of these clustes.
      Before the linear classifier is applied, the QRS waveforms are classified
      according to some special decision rules. 38 half-hour standard database is used
      to test the technique presented in this paper. The result shows t hat accuracy
      rate of PVC detection is better than 95%.

PMID- 9647623
TI  - [An instrument for estimating human body composition using impedance
      measurement].
AB  - According to the impedance feature of biological tissue, the instrument was
      designed at 1, 5, 10, 50, 100kHz to measure human impedance, and then to
      calculate human FAT, FFM, FAT%, TBW, ECW, ICW and so on. A 8031 singlechip
      microprocessor contacuting used as a control center in the instrument. The part
      of electric circuit contacuting human body in the instrument was unreally
      earthing. The instrument was safty, effective, repeatable, and easily
      manpulative. Prelimintary clinical experiment showed the results measured with
      the instrument could effectively reflect practical, status of human composition.

PMID- 9647624
TI  - [The research and application of uroflow rate measuring].
AB  - Using A/D converter acquiring uroflowrate is introduced in this paper. The
      uroflowrate curve is analysed and displayed by computer in real time. The
      programming of uroflowrate curve smoothing is presented.

PMID- 9647625
TI  - [The development of new-type soft X-ray tube].
AB  - This report is based on the technology of image and photo-taking and the creative
      mecaanism of X-ray. It also analyses the disadvanges of the outanode X-ray tube
      and the limitations of its clinical practice. Moreover, it clarifies the
      designing idea and the development result of a new-type soft X-ray tube.

PMID- 9647626
TI  - [The development of a fluid percussion device for brain injury of animals].
AB  - This paper discusses a fluid percussion device for brain injury. The injury is
      produced by striking the cork with a pendulum dropped from a known fall height to
      produce transient high pressure through a fluid transfer system. Experimental
      results show the device has the advantages of making a controllable, repeatable,
      and precise injury, and it can produce different levels of injury on different
      animals.

PMID- 9647627
TI  - [The development and application of the MJ-I electrode of stereo-location].
AB  - We use the MJ-I electrode of stereo-location insert intrabrain to measure the
      epileptic focus and to direct the surgical treating the patients with epilepsy.
      Excellent operative results were achieved.

PMID- 9647628
TI  - [Assessing indexes in the ECG data compression].
AB  - This paper describes various numerical assessing indexes in evaluating algorithms
      for the ECG data compression, such as numerical indexes of similarity (CC, RMS,
      PRD), indexes of error (amplitude error, peak error), efficiency of compression
      (Compression Ratio, bit rate), computing complexity, and so on. It also involves
      visual inspection which is more important in assessing algorithms.

PMID- 9647629
TI  - [ISFET transducer for clinical medicine application].

PMID- 9647630
TI  - Random shotgun fire.

PMID- 9647631
TI  - Odds on the FAST gene.

PMID- 9647632
TI  - WebWise: guide to the University of Washington Genome Center web site.

PMID- 9647633
TI  - Emerging patterns of comparative genome organization in some mammalian species as
      revealed by Zoo-FISH.
AB  - Although gene maps for a variety of evolutionarily diverged mammalian species
      have expanded rapidly during the past few years, until recently it has been
      difficult to precisely define chromosomal segments that are homologous between
      species. A solution to this problem has come from the development of Zoo-FISH,
      also known as cross-species chromosome painting. The use of Zoo-FISH to identify
      regions of chromosomal homology has allowed the transfer of information from map
      rich species such as human and mouse to a wide variety of other species. From a
      Zoo-FISH analysis spanning four mammalian orders (Primates, Artiodactyla,
      Carnivora, and Perissodactyla), and involving eight species (human, pig, cattle,
      Indian muntjac, cat, American mink, harbor seal, and horse), three distinct
      classes of synteny conservation have been designated: (1) conservation of whole
      chromosome synteny, (2) conservation of large chromosomal blocks, and (3)
      conservation of neighboring segment combinations. This analysis has also made it
      possible to identify a set of chromosome segments (based on human chromosome
      equivalents) that probably made up the karyotype of the common ancestor of the
      four orders. This approach provides a basis for developing a picture of the
      ancestral mammalian karyotype, but a full understanding will depend on studies
      encompassing more diverse combinations of mammalian orders.

PMID- 9647634
TI  - Large-scale taxonomic profiling of eukaryotic model organisms: a comparison of
      orthologous proteins encoded by the human, fly, nematode, and yeast genomes.
AB  - Comparisons of DNA and protein sequences between humans and model organisms,
      including the yeast Saccharomyces cerevisiae, the nematode Caenorhabditis
      elegans, and the fruit fly Drosophila melanogaster, are a significant source of
      information about the function of human genes and proteins in both normal and
      disease states. Important questions regarding cross-species sequence comparison
      remain unanswered, including (1) the fraction of the metabolic, signaling, and
      regulatory pathways that is shared by humans and the various model organisms; and
      (2) the validity of functional inferences based on sequence homology. We
      addressed these questions by analyzing the available fractions of human, fly,
      nematode, and yeast genomes for orthologous protein-coding genes, applying strict
      criteria to distinguish between candidate orthologous and paralogous proteins.
      Forty-two quartets of proteins could be identified as candidate orthologs. Twenty
      four Drosophila protein sequences were more similar to their human orthologs than
      the corresponding nematode proteins. Analysis of sequence substitutions and
      evolutionary distances in this data set revealed that most C. elegans genes are
      evolving more rapidly than Drosophila genes, suggesting that unequal evolutionary
      rates may contribute to the differences in similarity to human protein sequences.
      The available fraction of Drosophila proteins appears to lack representatives of
      many protein families and domains, reflecting the relative paucity of genomic
      data from this species.

PMID- 9647635
TI  - Ribonuclease k6: chromosomal mapping and divergent rates of evolution within the
      RNase A gene superfamily.
AB  - We have localized the gene encoding human RNase k6 to within approximately 120 kb
      on the long (q) arm of chromosome 14 by HAPPY mapping. With this information, the
      relative positions of the six human RNase A ribonucleases that have been mapped
      to this locus can be inferred. To further our understanding of the individual
      lineages comprising the RNase A superfamily, we have isolated and characterized
      10 novel genes orthologous to that encoding human RNase k6 from Great Ape, Old
      World, and New World monkey genomes. Each gene encodes a complete ORF with no
      less than 86% amino acid sequence identity to human RNase k6 with the eight
      cysteines and catalytic histidines (H15 and H123) and lysine (K38) typically
      observed among members of the RNase A superfamily. Interesting trends include an
      unusually low number of synonymous substitutions (Ks) observed among the New
      World monkey RNase k6 genes. When considering nonsilent mutations, RNase k6 is a
      relatively stable lineage, with a nonsynonymous substitution rate of 0.40 x 10(
      9) nonsynonymous substitutions/nonsynonymous site/year (ns/ns/yr). These results
      stand in contrast to those determined for the primate orthologs of the two
      closely related ribonucleases, the eosinophil-derived neurotoxin (EDN) and
      eosinophil cationic protein (ECP), which have incorporated nonsilent mutations at
      very rapid rates (1.9 x 10(-9) and 2.0 x 10(-9) ns/ns/yr, respectively). The
      uneventful trends observed for RNase k6 serve to spotlight the unique nature of
      EDN and ECP and the unusual evolutionary constraints to which these two
      ribonuclease genes must be responding. [The sequence data described in this paper
      have been submitted to the GenBank data library under accession nos. AF037081
      AF037090.]

PMID- 9647636
TI  - Evidence for the presence of insulin-dependent diabetes-associated alleles on the
      distal part of mouse chromosome 6.
AB  - Type 1 diabetes (IDDM) is a complex disorder with multifactorial and polygenic
      etiology. A genome-wide screen performed in a BC1 cohort of a cross between the
      nonobese diabetic (NOD) mouse with the diabetes-resistant feral strain PWK
      detected a major locus contributing to diabetes development on the distal part of
      chromosome 6. Unlike the majority of other Idd loci identified in intraspecific
      crosses, susceptibility is associated with the presence of the PWK allele.
      Genetic linkage analysis of congenic lines segregating PWK chromosome 6 segments
      in a NOD background confirmed the presence of the Idd locus within this region.
      The genetic interval defined by analysis of congenic animals showed a peak of
      significant linkage (P = 0.0005) centered on an approximately 9-cM region lying
      between D6Mit11 and D6Mit25 genetic markers within distal mouse chromosome 6.
      [Genetic markers polymorphic between the NOD and PWK strains are available as a
      supplement at http://www.genome.org]

PMID- 9647637
TI  - Chicken microchromosomes are hyperacetylated, early replicating, and gene rich.
AB  - The chicken karyotype consists of 39 chromosomes of which 33 are classed as
      microchromosomes (MICs). MICs contain about one third of genomic DNA. The
      majority of mapped chicken genes are assigned to macrochromosomes (MACs), but a
      recent study indicated that CpG islands (CGIs), which are associated with most
      vertebrate genes, map predominantly to MICs. The present work establishes that
      chicken genes are concentrated on MICs by several criteria. Acetylated (lysine 5)
      histone H4, which is strongly correlated with the presence of genes, is highly
      enriched on MICs by immunocytochemistry. In addition, detailed analysis of
      chicken cosmids shows that CGI-like fragments are approximately six times denser
      on MICs than on MACs. Published mapping of randomly chosen genes by fluorescent
      in situ hybridization (FISH) also shows a significant excess of microchromosomal
      assignments. Finally, the finding that MICs replicate during the first half of S
      phase is also compatible with the suggestion that MICs represent gene-rich DNA.
      We use the cosmid data to predict that approximately 75% of chicken genes are
      located on microchromosomes. [The sequence data described in this paper have been
      submitted to the GenBank data library under accession nos. AJ001643 and
      AJ001644.]

PMID- 9647638
TI  - Physical map of human 6p21.2-6p21.3: region flanking the centromeric end of the
      major histocompatibility complex.
AB  - We have physically mapped and cloned a 2.5-Mb chromosomal segment flanking the
      centromeric end of the major histocompatibility complex (MHC). We characterized
      in detail 27 YACs, 144 cosmids, 51 PACs, and 5 BACs, which will facilitate the
      complete genomic sequencing of this region of chromosome 6. The contig contains
      the genes encoding CSBP, p21, HSU09564 serine kinase, ZNF76, TCP-11, RPS10,
      HMGI(Y), BAK, and the human homolog of Tctex-7 (HSET). The GLO1 gene was mapped
      further centromeric in the 6p21.2-6p21.1 region toward TCTE-1. The gene order of
      the GLO1-HMGI(Y) segment in respect to the centromere is similar to the gene
      order in the mouse t-chromosome distal inversion, indicating that there is
      conservation in gene content but not gene order between humans and mice in this
      region. The close linkage of the BAK and CSBP genes to the MHC is of interest
      because of their possible involvement in autoimmune disease.

PMID- 9647639
TI  - A software system for data analysis in automated DNA sequencing.
AB  - Software for gel image analysis and base-calling in fluorescence-based sequencing
      consisting of two primary programs, BaseFinder and GelImager, is described.
      BaseFinder is a framework for trace processing, analysis, and base-calling.
      BaseFinder is highly extensible, allowing the addition of trace analysis and
      processing modules without recompilation. Powerful scripting capabilities
      combined with modularity and multilane handling allow the user to customize
      BaseFinder to virtually any type of trace processing. We have developed an
      extensive set of data processing and analysis modules for use with the program in
      fluorescence-based sequencing. GelImager is a framework for gel image
      manipulation. It can be used for gel visualization, lane retracking, and as a
      front end to the Washington University Getlanes program. The programs were
      designed using a cross-platform development environment, currently allowing them
      to run in Windows NT, Windows 95, Openstep/Mach, and Rhapsody. Work is ongoing to
      deploy the software on additional platforms, including Solaris, Linux, and MacOS.
      This software has been thoroughly tested and debugged in the analysis of >2
      million bp of raw sequence data from human chromosome 19 region q13. Overall
      sequencing accuracy was measured using a significant subset of these data,
      consisting of approximately 600 sequences, by comparing the individual shotgun
      sequences against the final assembled contigs. Also, results are reported from
      experiments that analyzed the accuracy of the software and two other well-known
      base-calling programs for sequencing the M13mp18 vector sequence. [The sequence
      data described in this paper have been submitted to the GenBank data library
      under accession no. AF025422]

PMID- 9647640
TI  - Rescue of targeted regions of mammalian chromosomes by in vivo recombination in
      yeast.
AB  - In contrast to other animal cell lines, the chicken pre-B cell lymphoma line,
      DT40, exhibits a high level of homologous recombination, which can be exploited
      to generate site-specific alterations in defined target genes or regions. In
      addition, the ability to generate human/chicken monochromosomal hybrids in the
      DT40 cell line opens a way for specific targeting of human genes. Here we
      describe a new strategy for direct isolation of a human chromosomal region that
      is based on targeting of the chromosome with a vector containing a yeast
      selectable marker, centromere, and an ARS element. This procedure allows rescue
      of the targeted region by transfection of total genomic DNA into yeast
      spheroplasts. Selection for the yeast marker results in isolation of chromosome
      sequences in the form of large circular yeast artificial chromosomes (YACs) up to
      170 kb in size containing the targeted region. These YACs are generated by
      homologous recombination in yeast between common repeated sequences in the
      targeted chromosomal fragment. Alternatively, the targeted region can be rescued
      as a linear YACs when a YAC fragmentation vector is included in the yeast
      transformation mixture. Because the entire isolation procedure of the chromosomal
      region, once a target insertion is obtained, can be accomplished in approximately
      1 week, the new method greatly expands the utility of the homologous
      recombinationproficient DT40 chicken cell system.

PMID- 9647641
TI  - Vector-hexamer PCR isolation of all insert ends from a YAC contig of the mouse
      Igh locus.
AB  - We have developed a simple PCR strategy, termed vector-hexamer PCR, that is
      unique in its ability to easily recover every insert end from large insert clones
      in YAC and BAC vectors. We used this method to amplify and isolate all insert
      ends from a YAC contig covering the mouse Igh locus. Seventy-seven ends were
      amplified and sequenced from 36 YAC clones from four libraries in the pYAC4
      vector. Unexpectedly, 40% of the insert ends of these YACs were LINE1 repeats.
      Nonrepetitive ends were suitable for use as probes on Southern blots of digested
      YACs to identify overlaps and construct a contig. The same strategy was used
      successfully to amplify insert ends from YACs in the pRML vector from the
      Whitehead Institute/MIT-820 mouse YAC library and from BACs in pBeloBAC11. The
      simplicity of this technique and its ability to isolate every end from large
      insert clones are of great utility in genomic investigation. [The nucleotide
      sequence data reported in this paper are accessible in GenBank under accession
      nos. B07512-B07598.]

PMID- 9647642
TI  - Suppression of steady-state, but not stimulus-induced NF-kappaB activity inhibits
      alphavirus-induced apoptosis.
AB  - Recent studies have established cell type- specific, proapoptotic, or
      antiapoptotic functions for the transcription factor NF-kappaB. In each of these
      studies, inhibitors of NF-kappaB activity have been present before the apoptotic
      stimulus, and so the role of stimulus- induced NF-kappaB activation in enhancing
      or inhibiting survival could not be directly assessed. Sindbis virus, an
      alphavirus, induces NF-kappaB activation and apoptosis in cultured cell lines. To
      address whether Sindbis virus- induced NF-kappaB activation is required for
      apoptosis, we used a chimeric Sindbis virus that expresses a superrepressor of NF
      kappaB activity. Complete suppression of virus-induced NF-kappaB activity neither
      prevents nor potentiates Sindbis virus-induced apoptosis. In contrast, inhibition
      of NF-kappaB activity before infection inhibits Sindbis virus-induced apoptosis.
      Our results demonstrate that suppression of steady-state, but not stimulus
      induced NF-kappaB activity, regulates expression of gene products required for
      Sindbis virus-induced death. Furthermore, we show that in the same cell line, NF
      kappaB can be proapoptotic or antiapoptotic depending on the death stimulus. We
      propose that the role of NF-kappaB in regulating apoptosis is determined by the
      death stimulus and by the timing of modulating NF-kappaB activity relative to the
      death stimulus.

PMID- 9647643
TI  - Localization, dynamics, and protein interactions reveal distinct roles for ER and
      Golgi SNAREs.
AB  - ER-to-Golgi transport, and perhaps intraGolgi transport involves a set of
      interacting soluble N-ethylmaleimide-sensitive factor attachment protein receptor
      (SNARE) proteins including syntaxin 5, GOS-28, membrin, rsec22b, and rbet1. By
      immunoelectron microscopy we find that rsec22b and rbet1 are enriched in COPII
      coated vesicles that bud from the ER and presumably fuse with nearby vesicular
      tubular clusters (VTCs). However, all of the SNAREs were found on both COPII- and
      COPI-coated membranes, indicating that similar SNARE machinery directs both
      vesicle pathways. rsec22b and rbet1 do not appear beyond the first Golgi
      cisterna, whereas syntaxin 5 and membrin penetrate deeply into the Golgi stacks.
      Temperature shifts reveal that membrin, rsec22b, rbet1, and syntaxin 5 are
      present together on membranes that rapidly recycle between peripheral and Golgi
      centric locations. GOS-28, on the other hand, maintains a fixed localization in
      the Golgi. By immunoprecipitation analysis, syntaxin 5 exists in at least two
      major subcomplexes: one containing syntaxin 5 (34-kD isoform) and GOS-28, and
      another containing syntaxin 5 (41- and 34-kD isoforms), membrin, rsec22b, and
      rbet1. Both subcomplexes appear to involve direct interactions of each SNARE with
      syntaxin 5. Our results indicate a central role for complexes among rbet1,
      rsec22b, membrin, and syntaxin 5 (34 and 41 kD) at two membrane fusion
      interfaces: the fusion of ER-derived vesicles with VTCs, and the assembly of VTCs
      to form cis-Golgi elements. The 34-kD syntaxin 5 isoform, membrin, and GOS-28 may
      function in intraGolgi transport.

PMID- 9647644
TI  - The SNARE machinery is involved in apical plasma membrane trafficking in MDCK
      cells.
AB  - We have investigated the controversial involvement of components of the SNARE
      (soluble N-ethyl maleimide-sensitive factor [NSF] attachment protein [SNAP]
      receptor) machinery in membrane traffic to the apical plasma membrane of
      polarized epithelial (MDCK) cells. Overexpression of syntaxin 3, but not of
      syntaxins 2 or 4, caused an inhibition of TGN to apical transport and apical
      recycling, and leads to an accumulation of small vesicles underneath the apical
      plasma membrane. All other tested transport steps were unaffected by syntaxin 3
      overexpression. Botulinum neurotoxin E, which cleaves SNAP-23, and antibodies
      against alpha-SNAP inhibit both TGN to apical and basolateral transport in a
      reconstituted in vitro system. In contrast, we find no evidence for an
      involvement of N-ethyl maleimide-sensitive factor in TGN to apical transport,
      whereas basolateral transport is NSF-dependent. We conclude that syntaxin 3, SNAP
      23, and alpha-SNAP are involved in apical membrane fusion. These results
      demonstrate that vesicle fusion with the apical plasma membrane does not use a
      mechanism that is entirely unrelated to other cellular membrane fusion events,
      but uses isoforms of components of the SNARE machinery, which suggests that they
      play a role in providing specificity to polarized membrane traffic.

PMID- 9647645
TI  - The mammalian calcium-binding protein, nucleobindin (CALNUC), is a Golgi resident
      protein.
AB  - We have identified CALNUC, an EF-hand, Ca2+-binding protein, as a Golgi resident
      protein. CALNUC corresponds to a previously identified EF-hand/calcium-binding
      protein known as nucleobindin. CALNUC interacts with Galphai3 subunits in the
      yeast two-hybrid system and in GST-CALNUC pull-down assays. Analysis of deletion
      mutants demonstrated that the EF-hand and intervening acidic regions are the site
      of CALNUC's interaction with Galphai3. CALNUC is found in both cytosolic and
      membrane fractions. The membrane pool is tightly associated with the luminal
      surface of Golgi membranes. CALNUC is widely expressed, as it is detected by
      immunofluorescence in the Golgi region of all tissues and cell lines examined. By
      immunoelectron microscopy, CALNUC is localized to cis-Golgi cisternae and the cis
      Golgi network (CGN). CALNUC is the major Ca2+-binding protein detected by 45Ca2+
      binding assay on Golgi fractions. The properties of CALNUC and its high homology
      to calreticulin suggest that it may play a key role in calcium homeostasis in the
      CGN and cis-Golgi cisternae.

PMID- 9647646
TI  - G protein beta subunit-null mutants are impaired in phagocytosis and chemotaxis
      due to inappropriate regulation of the actin cytoskeleton.
AB  - Chemotaxis and phagocytosis are basically similar in cells of the immune system
      and in Dictyostelium amebae. Deletion of the unique G protein beta subunit in D.
      discoideum impaired phagocytosis but had little effect on fluid-phase
      endocytosis, cytokinesis, or random motility. Constitutive expression of wild
      type beta subunit restored phagocytosis and normal development. Chemoattractants
      released by cells or bacteria trigger typical transient actin polymerization
      responses in wild-type cells. In beta subunit-null cells, and in a series of beta
      subunit point mutants, these responses were impaired to a degree that correlated
      with the defect in phagocytosis. Image analysis of green fluorescent protein
      actin transfected cells showed that beta subunit- null cells were defective in
      reshaping the actin network into a phagocytic cup, and eventually a phagosome, in
      response to particle attachment. Our results indicate that signaling through
      heterotrimeric G proteins is required for regulating the actin cytoskeleton
      during phagocytic uptake, as previously shown for chemotaxis. Inhibitors of
      phospholipase C and intracellular Ca2+ mobilization inhibited phagocytosis,
      suggesting the possible involvement of these effectors in the process.

PMID- 9647647
TI  - Claudin-1 and -2: novel integral membrane proteins localizing at tight junctions
      with no sequence similarity to occludin.
AB  - Occludin is the only known integral membrane protein localizing at tight
      junctions (TJ), but recent targeted disruption analysis of the occludin gene
      indicated the existence of as yet unidentified integral membrane proteins in TJ.
      We therefore re-examined the isolated junction fraction from chicken liver, from
      which occludin was first identified. Among numerous components of this fraction,
      only a broad silver-stained band approximately 22 kD was detected with the
      occludin band through 4 M guanidine-HCl extraction as well as sonication followed
      by stepwise sucrose density gradient centrifugation. Two distinct peptide
      sequences were obtained from the lower and upper halves of the broad band, and
      similarity searches of databases allowed us to isolate two full-length cDNAs
      encoding related mouse 22-kD proteins consisting of 211 and 230 amino acids,
      respectively. Hydrophilicity analysis suggested that both bore four transmembrane
      domains, although they did not show any sequence similarity to occludin.
      Immunofluorescence and immunoelectron microscopy revealed that both proteins
      tagged with FLAG or GFP were targeted to and incorporated into the TJ strand
      itself. We designated them as "claudin-1" and "claudin-2", respectively. Although
      the precise structure/function relationship of the claudins to TJ still remains
      elusive, these findings indicated that multiple integral membrane proteins with
      four putative transmembrane domains, occludin and claudins, constitute TJ
      strands.

PMID- 9647648
TI  - Mechanical fluctuations of the membrane-skeleton are dependent on F-actin ATPase
      in human erythrocytes.
AB  - Cell membrane fluctuations (CMF) of human erythrocytes, measured by point dark
      field microscopy, were shown to depend, to a large extent, on intracellular MgATP
      (Levin, S.V., and R. Korenstein. 1991. Biophys. J. 60:733-737). The present study
      extends that investigation and associates CMF with F-actin's ATPase activity.
      MgATP was found to reconstitute CMF in red blood cell (RBC) ghosts and RBC
      skeletons to their levels in intact RBCs, with an apparent Kd of 0.29 mM.
      However, neither non-hydrolyzable ATP analogues (AMP-PNP, ATPgammaS) nor
      hydrolyzable ones (ITP, GTP), were able to elevate CMF levels. The inhibition of
      ATPase activity associated with the RBC's skeleton, carried out either by the
      omission of the MgATP substrate or by the use of several inhibitors (vanadate,
      phalloidin, and DNase I), resulted in a strong decrease of CMF. We suggest that
      the actin's ATPase, located at the pointed end of the short actin filament, is
      responsible for the MgATP stimulation of CMF in RBCs.

PMID- 9647649
TI  - C-Nap1, a novel centrosomal coiled-coil protein and candidate substrate of the
      cell cycle-regulated protein kinase Nek2.
AB  - Nek2 (for NIMA-related kinase 2) is a mammalian cell cycle-regulated kinase
      structurally related to the mitotic regulator NIMA of Aspergillus nidulans. In
      human cells, Nek2 associates with centrosomes, and overexpression of active Nek2
      has drastic consequences for centrosome structure. Here, we describe the
      molecular characterization of a novel human centrosomal protein, C-Nap1 (for
      centrosomal Nek2-associated protein 1), first identified as a Nek2-interacting
      protein in a yeast two-hybrid screen. Antibodies raised against recombinant C
      Nap1 produced strong labeling of centrosomes by immunofluorescence, and
      immunoelectron microscopy revealed that C-Nap1 is associated specifically with
      the proximal ends of both mother and daughter centrioles. On Western blots, anti
      C-Nap1 antibodies recognized a large protein (>250 kD) that was highly enriched
      in centrosome preparations. Sequencing of overlapping cDNAs showed that C-Nap1
      has a calculated molecular mass of 281 kD and comprises extended domains of
      predicted coiled-coil structure. Whereas C-Nap1 was concentrated at centrosomes
      in all interphase cells, immunoreactivity at mitotic spindle poles was strongly
      diminished. Finally, the COOH-terminal domain of C-Nap1 could readily be
      phosphorylated by Nek2 in vitro, as well as after coexpression of the two
      proteins in vivo. Based on these findings, we propose a model implicating both
      Nek2 and C-Nap1 in the regulation of centriole-centriole cohesion during the cell
      cycle.

PMID- 9647650
TI  - A role for NIMA in the nuclear localization of cyclin B in Aspergillus nidulans.
AB  - NIMA promotes entry into mitosis in late G2 by some mechanism that is after
      activation of the Aspergillus nidulans G2 cyclin-dependent kinase,
      NIMXCDC2/NIMECyclin B. Here we present two independent lines of evidence which
      indicate that this mechanism involves control of NIMXCDC2/NIMECyclin B
      localization. First, we found that NIMECyclin B localized to the nucleus and the
      nucleus-associated organelle, the spindle pole body, in a NIMA-dependent manner.
      Analysis of cells from asynchronous cultures, synchronous cultures, and cultures
      arrested in S or G2 showed that NIMECyclin B was predominantly nuclear during
      interphase, with maximal nuclear accumulation in late G2. NIMXCDC2 colocalized
      with NIMECyclin B in G2 cells. Although inactivation of NIMA using either the
      nimA1 or nimA5 temperature-sensitive mutations blocked cells in G2,
      NIMXCDC2/NIMECyclin B localization was predominantly cytoplasmic rather than
      nuclear. Second, we found that nimA interacts genetically with sonA, which is a
      homologue of the yeast nucleocytoplasmic transporter GLE2/RAE1. Mutations in sonA
      were identified as allele-specific suppressors of nimA1. The sonA1 suppressor
      alleviated the nuclear division and NIMECyclin B localization defects of nimA1
      cells without markedly increasing NIMXCDC2 or NIMA kinase activity. These results
      indicate that NIMA promotes the nuclear localization of the NIMXCDC2/ NIMECyclin
      B complex, by a process involving SONA. This mechanism may be involved in
      coordinating the functions of NIMXCDC2 and NIMA in the regulation of mitosis.

PMID- 9647651
TI  - Structural analysis of Drosophila merlin reveals functional domains important for
      growth control and subcellular localization.
AB  - Merlin, the product of the Neurofibromatosis type 2 (NF2) tumor-suppressor gene,
      is a member of the protein 4.1 superfamily that is most closely related to ezrin,
      radixin, and moesin (ERM). NF2 is a dominantly inherited disease characterized by
      the formation of bilateral acoustic schwannomas and other benign tumors
      associated with the central nervous system. To understand its cellular functions,
      we are studying a Merlin homologue in Drosophila. As is the case for NF2 tumors,
      Drosophila cells lacking Merlin function overproliferate relative to their
      neighbors. Using in vitro mutagenesis, we define functional domains within Merlin
      required for proper subcellular localization and for genetic rescue of lethal
      Merlin alleles. Remarkably, the results of these experiments demonstrate that all
      essential genetic functions reside in the plasma membrane- associated NH2
      terminal 350 amino acids of Merlin. Removal of a seven-amino acid conserved
      sequence within this domain results in a dominant-negative form of Merlin that is
      stably associated with the plasma membrane and causes overproliferation when
      expressed ectopically in the wing. In addition, we provide evidence that the COOH
      terminal region of Merlin has a negative regulatory role, as has been shown for
      ERM proteins. These results provide insights into the functions and functional
      organization of a novel tumor suppressor gene.

PMID- 9647652
TI  - Activity-dependent regulation of dendritic BC1 RNA in hippocampal neurons in
      culture.
AB  - Several neuronal RNAs have been identified in dendrites, and it has been
      suggested that the dendritic location of these RNAs may be relevant to the
      spatiotemporal regulation of mosaic postsynaptic protein repertoires through
      transsynaptic activity. Such regulation would require that dendritic RNAs
      themselves, or at least some of them, be subject to physiological control. We
      have therefore examined the functional regulation of somatodendritic expression
      levels of dendritic BC1 RNA in hippocampal neurons in culture. BC1 RNA, an RNA
      polymerase III transcript that is a component of a ribonucleoprotein particle,
      became first detectable in somatodendritic domains of developing hippocampal
      neurons at times of initial synapse formation. BC1 RNA was identified only in
      such neurons that had established synapses on cell bodies and/or developing
      dendritic arbors. When synaptic contact formation was initiated later in low
      density cultures, BC1 expression was coordinately delayed. Inhibition of neuronal
      activity in hippocampal neurons resulted in a substantial but reversible
      reduction of somatodendritic BC1 expression. We conclude that expression of BC1
      RNA in somatic and dendritic domains of hippocampal neurons is regulated in
      development, and is dependent upon neuronal activity. These results establish
      (for the first time to our knowledge) that an RNA polymerase III transcript can
      be subject to control through physiological activity in nerve cells.

PMID- 9647653
TI  - A role of tyrosine phosphatase in acetylcholine receptor cluster dispersal and
      formation.
AB  - Innervation of the skeletal muscle involves local signaling, leading to
      acetylcholine receptor (AChR) clustering, and global signaling, manifested by the
      dispersal of preexisting AChR clusters (hot spots). Receptor tyrosine kinase
      (RTK) activation has been shown to mediate AChR clustering. In this study, the
      role of tyrosine phosphatase (PTPase) in the dispersal of hot spots was examined.
      Hot spot dispersal in cultured Xenopus muscle cells was initiated immediately
      upon the presentation of growth factor-coated beads that induce both AChR cluster
      formation and dispersal. Whereas the density of AChRs decreased with time, the
      fine structure of the hot spot remained relatively constant. Although AChR,
      rapsyn, and phosphotyrosine disappeared, a large part of the original hot spot
      associated cytoskeleton remained. This suggests that the dispersal involves the
      removal of a key linkage between the receptor and its cytoskeletal
      infrastructure. The rate of hot spot dispersal is inversely related to its
      distance from the site of synaptic stimulation, implicating the diffusible nature
      of the signal. PTPase inhibitors, such as pervanadate or phenylarsine oxide,
      inhibited hot spot dispersal. In addition, they also affected the formation of
      new clusters in such a way that AChR microclusters extended beyond the boundary
      set by the clustering stimuli. Furthermore, by introducing a constitutively
      active PTPase into cultured muscle cells, hot spots were dispersed in a stimulus-
      independent fashion. This effect of exogenous PTPase was also blocked by
      pervanadate. These results implicate a role of PTPase in AChR cluster dispersal
      and formation. In addition to RTK activation, synaptic stimulation may also
      activate PTPase which acts globally to destabilize preexisting AChR hot spots and
      locally to facilitate AChR clustering in a spatially discrete manner by
      countering the action of RTKs.

PMID- 9647654
TI  - Molecular dissection of the Rho-associated protein kinase (p160ROCK)-regulated
      neurite remodeling in neuroblastoma N1E-115 cells.
AB  - A critical role for the small GTPase Rho and one of its targets, p160ROCK (a Rho
      associated coiled coil-forming protein kinase), in neurite remodeling was
      examined in neuroblastoma N1E-115 cells. Using wild-type and a dominant-negative
      form of p160ROCK and a p160ROCK-specific inhibitor, Y-27632, we show here that
      p160ROCK activation is necessary and sufficient for the agonist-induced neurite
      retraction and cell rounding. The neurite retraction was accompanied by elevated
      phosphorylation of myosin light chain and the disassembly of the intermediate
      filaments and microtubules. Y-27632 blocked both neurite retraction and the
      elevation of myosin light chain phosphorylation in a similar concentration
      dependent manner. On the other hand, suppression of p160ROCK activity by
      expression of a dominant-negative form of p160ROCK induced neurites in the
      presence of serum by inducing the reassembly of the intermediate filaments and
      microtubules. The neurite outgrowth by the p160ROCK inhibition was blocked by
      coexpression of dominant-negative forms of Cdc42 and Rac, indicating that
      p160ROCK constitutively and negatively regulates neurite formation at least in
      part by inhibiting activation of Cdc42 and Rac. The assembly of microtubules and
      intermediate filaments to form extended processes by inhibitors of the Rho-ROCK
      pathway was also observed in Swiss 3T3 cells. These results indicate that
      Rho/ROCK-dependent tonic inhibition of cell process extension is exerted via
      activation of the actomysin-based contractility, in conjunction with a
      suppression of assembly of intermediate filaments and microtubules in many cell
      types including, but not exclusive to, neuronal cells.

PMID- 9647655
TI  - Src family tyrosine kinase regulates intracellular pH in cardiomyocytes.
AB  - The Anion Cl-/HCO3- Exchangers AE1, AE2, and AE3 are membrane pH regulatory ion
      transporters ubiquitously expressed in vertebrate tissues. Besides relieving
      intracellular alkaline and CO2 loads, the AEs have an important function during
      development and cell death and play a central role in such cellular properties as
      cell shape, metabolism, and contractility. The activity of AE(s) are regulated by
      neurohormones. However, little is known as to the intracellular signal
      transduction pathways that underlie this modulation. We show here that, in
      cardiomyocytes that express both AE1 and AE3, the purinergic agonist, ATP,
      triggers activation of anion exchange. The AE activation is observed in cells in
      which AE3 expression was blocked but not in cells microinjected with neutralizing
      anti-AE1 antibodies. ATP induces tyrosine phosphorylation of AE1, activation of
      the tyrosine kinase Fyn, and association of both Fyn and FAK with AE1. Inhibition
      of Src family kinases in vivo by genistein, herbimycin A, or ST638 prevents
      purinergic activation of AE1. Microinjection of either anti-Cst.1 antibody or
      recombinant CSK, both of which prevent activation of Src family kinase,
      significantly decreases ATP-induced activation of AE. Microinjection of an anti
      FAK antibody as well as expression in cardiomyocytes of Phe397 FAK dominant
      negative mutant, also prevents purinergic activation of AE. Therefore, tyrosine
      kinases play a key role in acute regulation of intracellular pH and thus in cell
      function including excitation-contraction coupling of the myocardium.

PMID- 9647656
TI  - Activation of the MAP kinase pathway by FGF-1 correlates with cell proliferation
      induction while activation of the Src pathway correlates with migration.
AB  - FGF regulates both cell migration and proliferation by receptor-dependent
      induction of immediate-early gene expression and tyrosine phosphorylation of
      intracellular polypeptides. Because little is known about the disparate nature of
      intracellular signaling pathways, which are able to discriminate between cell
      migration and proliferation, we used a washout strategy to examine the
      relationship between immediate-early gene expression and tyrosine phosphorylation
      with respect to the potential of cells either to migrate or to initiate DNA
      synthesis in response to FGF-1. We demonstrate that transient exposure to FGF-1
      results in a significant decrease in Fos transcript expression and a decrease in
      tyrosine phosphorylation of the FGFR-1, p42(mapk), and p44(mapk). Consistent with
      these biochemical effects, we demonstrate that attenuation in the level of DNA
      synthesis such that a 1.5-h withdrawal is sufficient to return the population to
      a state similar to quiescence. In contrast, the level of Myc mRNA, the activity
      of Src, the tyrosine phosphorylation of cortactin, and the FGF-1-induced
      redistribution of cortactin and F-actin were unaffected by transient FGF-1
      stimulation. These biochemical responses are consistent with an implied
      uncompromised migratory potential of the cells in response to growth factor
      withdrawal. These results suggest a correlation between Fos expression and the
      mitogen-activated protein kinase pathway with initiation of DNA synthesis and a
      correlation between high levels of Myc mRNA and Src kinase activity with the
      regulation of cell migration.

PMID- 9647657
TI  - Fibroblast growth factor-2 (FGF-2) induces vascular endothelial growth factor
      (VEGF) expression in the endothelial cells of forming capillaries: an autocrine
      mechanism contributing to angiogenesis.
AB  - FGF-2 and VEGF are potent angiogenesis inducers in vivo and in vitro. Here we
      show that FGF-2 induces VEGF expression in vascular endothelial cells through
      autocrine and paracrine mechanisms. Addition of recombinant FGF-2 to cultured
      endothelial cells or upregulation of endogenous FGF-2 results in increased VEGF
      expression. Neutralizing monoclonal antibody to VEGF inhibits FGF-2-induced
      endothelial cell proliferation. Endogenous 18-kD FGF-2 production upregulates
      VEGF expression through extracellular interaction with cell membrane receptors;
      high-Mr FGF-2 (22-24-kD) acts via intracellular mechanism(s). During angiogenesis
      induced by FGF-2 in the mouse cornea, the endothelial cells of forming
      capillaries express VEGF mRNA and protein. Systemic administration of
      neutralizing VEGF antibody dramatically reduces FGF-2-induced angiogenesis.
      Because occasional fibroblasts or other cell types present in the corneal stroma
      show no significant expression of VEGF mRNA, these findings demonstrate that
      endothelial cell-derived VEGF is an important autocrine mediator of FGF-2-induced
      angiogenesis. Thus, angiogenesis in vivo can be modulated by a novel mechanism
      that involves the autocrine action of vascular endothelial cell-derived FGF-2 and
      VEGF.

PMID- 9647658
TI  - The laminin-nidogen complex is a ligand for a specific splice isoform of the
      transmembrane protein tyrosine phosphatase LAR.
AB  - Leukocyte antigen-related protein (LAR) is a prototype for a family of
      transmembrane protein tyrosine phosphatases whose extracellular domain is
      composed of three Ig and several fibronectin type III (FnIII) domains. Complex
      alternative splicing of the LAR-FnIII domains 4-8 has been observed. The
      extracellular matrix laminin-nidogen complex was identified as a ligand for the
      LAR-FnIII domain 5 (Fn5) using a series of GST-LAR-FnIII domain fusion proteins
      and testing them in in vitro ligand-binding assays. LAR- laminin-nidogen binding
      was regulated by alternative splicing of a small exon within the LAR-Fn5 so that
      inclusion of this exon sequence resulted in disruption of the laminin-nidogen
      binding activity. Long cellular processes were observed when HeLa cells were
      plated on laminin-nidogen, but not when plated on a fibronectin surface. Indirect
      immunofluorescent antibody staining revealed high expression of LAR in a punctate
      pattern, throughout the length of these cellular processes observed on laminin
      nidogen. Antibody-induced cross-linking of LAR inhibited formation of these
      cellular processes, and inhibition was correlated with changes in cellular actin
      cytoskeletal structure. Thus, LAR-laminin-nidogen binding may play a role in
      regulating cell signaling induced by laminin-nidogen, resulting in cell
      morphological changes.

PMID- 9647659
TI  - Complementary roles for receptor clustering and conformational change in the
      adhesive and signaling functions of integrin alphaIIb beta3.
AB  - Integrin alphaIIb beta3 mediates platelet aggregation and "outside-in" signaling.
      It is regulated by changes in receptor conformation and affinity and/or by
      lateral diffusion and receptor clustering. To document the relative contributions
      of conformation and clustering to alphaIIb beta3 function, alphaIIb was fused at
      its cytoplasmic tail to one or two FKBP12 repeats (FKBP). These modified alphaIIb
      subunits were expressed with beta3 in CHO cells, and the heterodimers could be
      clustered into morphologically detectable oligomers upon addition of AP1510, a
      membrane-permeable, bivalent FKBP ligand. Integrin clustering by AP1510 caused
      binding of fibrinogen and a multivalent (but not monovalent) fibrinogen-mimetic
      antibody. However, ligand binding due to clustering was only 25-50% of that
      observed when alphaIIb beta3 affinity was increased by an activating antibody or
      an activating mutation. The effects of integrin clustering and affinity
      modulation were additive, and clustering promoted irreversible ligand binding.
      Clustering of alphaIIb beta3 also promoted cell adhesion to fibrinogen or von
      Willebrand factor, but not as effectively as affinity modulation. However,
      clustering was sufficient to trigger fibrinogen-independent tyrosine
      phosphorylation of pp72(Syk) and fibrinogen-dependent phosphorylation of
      pp125(FAK), even in non-adherent cells. Thus, receptor clustering and affinity
      modulation play complementary roles in alphaIIb beta3 function. Affinity
      modulation is the predominant regulator of ligand binding and cell adhesion, but
      clustering increases these responses further and triggers protein tyrosine
      phosphorylation, even in the absence of affinity modulation. Both affinity
      modulation and clustering may be needed for optimal function of alphaIIb beta3 in
      platelets.

PMID- 9647660
TI  - Xanthine oxidase reaction with nitric oxide and peroxynitrite.
AB  - Nitric oxide (.NO) and peroxynitrite (ONOO-) inhibit enzymes that depend on metal
      cofactors or oxidizable amino acids for activity. Since xanthine oxidase (XO) is
      a 2(2Fe2S) enzyme having essential sulfhydryl groups linked with Mo-pterin
      cofactor function, the influence of .NO and ONOO- on purified bovine XO was
      determined. Physiological (</=1 microM) and supraphysiological (</=100 microM)
      concentrations of dissolved .NO gas did not inhibit the catalytic activity or
      alter the spectral characteristics of XO at 25 degreesC and pH 7.0, differing
      from reports showing XO inhibition by .NO. The apparent decrease in XO activity
      observed previously was the result of depressed rates of uric acid accumulation
      in XO assay systems, due to ONOO--mediated oxidation of uric acid upon reaction
      of residual .NO with XO-derived superoxide (O*-2). Nitric oxide derived from S
      nitrosoglutathione also did not inhibit cultured vascular endothelial cell XO
      activity. In contrast, purified and vascular endothelial cell catalase, a heme
      enzyme reversibly inhibited by .NO, was inhibited by similar concentrations and
      rates of production of . NO. In contrast to .NO, ONOO- inhibited XO (0.2 microM,
      50 mU/ml) with an IC50 of 57 microM (for 3 microM/min infusion of ONOO-) or 120
      microM (for bolus addition of ONOO-). Addition of 1% bovine serum albumin, 50
      microM xanthine, or 10 microM uric acid protected XO from inactivation by ONOO-.
      Thus, in the presence of purine substrates and other more readily oxidized
      components of the biological milieu, XO should not be inhibited by either .NO or
      ONOO-. These observations reveal that .NO will not serve as an indirect
      antioxidant by inhibiting XO-derived production of reactive species and that the
      XO-derived products O*-2 and uric acid readily modify the reactivities of .NO and
      ONOO-.

PMID- 9647661
TI  - Spontaneous conversion of L-dehydroascorbic acid to L-ascorbic acid and L
      erythroascorbic acid.
AB  - Dehydroascorbic acid, an oxidation product of ascorbic acid (vitamin C),
      spontaneously decomposed at neutral and higher pH levels to form three products
      that could be quantitated by HPLC-electrochemical analysis. One of the products
      was ascorbic acid, suggesting that dehydroascorbic acid was reduced to ascorbic
      acid without adding an exogenous reductant. The major newly produced compound was
      almost identical to ascorbic acid by UV spectroscopy, which therefore potentially
      interfered in the study of ascorbic acid metabolism. The ascorbic acid-like
      compound was isolated by reversed-phase HPLC and identified as L-erythroascorbic
      acid by mass spectrometry. Fe(II) and Cu(I) increased, whereas desferrioxamine, a
      potent iron chelator, inhibited L-erythroascorbic acid production. Phosphate,
      used as buffer, and cyanide greatly enhanced dehydroascorbic acid conversion to L
      erythroascorbic acid. The identification of L-erythroascorbic acid and its
      quantitation by an electrochemical method provides a useful tool for future study
      of dehydroascorbic acid metabolism.

PMID- 9647662
TI  - A serine proteinase inactivator inhibits chondrocyte-mediated cartilage
      proteoglycan breakdown occurring in response to proinflammatory cytokines.
AB  - The role played by serine proteinases with trypsin-like specificity in
      chondrocyte-mediated cartilage proteoglycan breakdown was investigated by use of
      a selective proteinase inactivator, 7-amino-4-chloro-3-(-3
      isothiureidopropoxy)isocoumarin, in explant culture systems. This compound was a
      rapid inactivator of urokinase-type plasminogen activator. It potently inhibited
      interleukin 1- and tumor necrosis factor-stimulated proteoglycan release from
      both nasal and articular cartilage. Its less potent inhibition of basal and
      retinoic acid-stimulated release appeared to be due to cytotoxic effects. The
      functional half-life of the inactivator in culture medium was 95 min, and its
      concentration in cartilage was 2.5-fold higher than in the surrounding medium.
      Following spontaneous hydrolysis the breakdown products of the inactivator were
      unable to inhibit proteoglycan release. Trypsin-like activity was demonstrated by
      enzyme histochemistry to be chondrocyte-associated and inhibited by the serine
      proteinase inactivator. Cell-associated and secreted plasminogen activator
      activity was detected by zymography. These results suggest the involvement of a
      serine proteinase(s) with trypsin-like specificity, possibly urokinase-type
      plasminogen activator, in chondrocyte-mediated cartilage proteoglycan breakdown
      occurring as a result of stimulation with proinflammatory cytokines. Basal
      proteoglycan breakdown may occur via a different pathway. Our findings point to a
      pathological role for serine proteinase(s) in the development of cartilage
      diseases such as arthritis, possibly in a cascade which results in the activation
      of the enzyme(s) directly responsible for proteoglycan breakdown. It remains to
      be shown whether the target serine proteinase is urokinase-type plasminogen
      activator.

PMID- 9647663
TI  - Purification to homogeneity and properties of plant glucosidase I.
AB  - Glucosidase I was purified about 3600-fold to apparent homogeneity from the
      microsomal fraction of mung bean seedlings. The purified enzyme removed the
      terminal alpha1,2-linked glucose from Glc3Man9GlcNAc2-peptide or the
      endoglucosaminidase H (Endo H)-released oligosaccharide. Glucosidase I activity
      was inhibited by kojibiose [Glc(alpha1-2)Glc], but not by other glucose
      disaccharides. Removal of up to four mannose residues from the N-linked
      oligosaccharide had little effect on its utilization as a substrate for
      glucosidase I. The enzyme had a subunit molecular weight of 97 kDa on SDS gels
      and this was shifted to 94 kDa after treatment with Endo H or Endo F, suggesting
      that glucosidase I is an N-glycoprotein having one oligomannose-type
      oligosaccharide. Amino acid sequences of this enzyme showed considerable identity
      to the enzyme cloned from a human hippocampus cDNA library. The enzyme was
      inhibited by castanospermine, deoxynojirimycin, MDL, and trehazolin, but not by
      australine or kifunensine. On the other hand, the other processing glucosidase,
      glucosidase II, is sensitive to inhibition by australine, but not by trehazolin.
      Thus, these two inhibitors are useful to distinguish glucosidase I from
      glucosidase II. The mung bean glucosidase I is quite sensitive to the histidine
      modifying reagent diethyl pyrocarbonate, whereas the pig liver glucosidase I is
      not. On the other hand, pig liver and pig brain glucosidase I preparations are
      sensitive to the sulfhydryl reagent NEM (N-ethylmaleimide), whereas the plant
      enzyme is not. These sensitivities to amino acid modifiers suggest significant
      differences between the plant and animal glucosidase I, in terms of catalytic
      site or protein conformation.

PMID- 9647664
TI  - Calcium-induced quenching of intrinsic fluorescence in brain myosin V is linked
      to dissociation of calmodulin light chains.
AB  - Myosin V isolated from chick brain (BM V) is a multimeric protein of about 640
      kDa consisting of two intertwined heavy chains of 212 kDa and multiple light
      chains of 10 to 20 kDa. A distinctive feature of the heavy chain is an extended
      neck region with six consensus IQ sites for the binding of calmodulin (CaM) and
      myosin light chains. The actin-activated MgATPase has been shown to require >/=1
      microM Ca2+ for full activity, and evidence points to a myosin-linked regulatory
      system where the CaM light chains participate as modulators for the Ca2+ signal.
      Still, the precise mechanism of Ca2+ regulation remains unknown. In the present
      study we have used the intrinsic tryptophan fluorescence of native BM V to
      monitor conformational changes of BM V induced by Ca2+, and we relate these
      changes to CaM dissociation from the BM V molecule. The fluorescence intensity
      decreases approximately 17% upon addition of sub-micromolar concentrations of
      Ca2+ (K0.5 = 0.038 microM). This decrease in fluorescence, which is dominated by
      a conformational change in the heavy chain, can be reversed by addition of 1, 2
      di(2-aminoethoxy)ethane-N,N,N',N'tetraacetic acid (EGTA) followed by an excess of
      CaM, but not by addition of EGTA alone. Gel filtration of native BM V using HPLC
      shows that CaM is partially dissociated from the heavy chain in EGTA and
      dissociates further upon addition of sub-micromolar concentrations of Ca2+. These
      observations suggest that the affinity of CaM for at least one of the IQ sites on
      the BM V heavy chain decreases with Ca2+ and that the Ca2+ concentration required
      for this effect is lower than that needed to activate acto-BM V. Using a
      cosedimentation assay in the presence of actin, we also observe partial
      dissociation of CaM when Ca2+ is absent, but now the addition of Ca2+ has a
      biphasic effect: sub-micromolar Ca2+ concentrations lead to reassociation of CaM
      with the heavy chain, followed by dissociation when Ca2+ exceeds 5-10 microM.
      Thus, the binding of CaM to BM V is affected by both actin and Ca2+.

PMID- 9647665
TI  - Antiradical and chelating effects in flavonoid protection against silica-induced
      cell injury.
AB  - Quercetin, dihydroquercetin, and rutin are capable of scavenging superoxide anion
      (rate constants of the reaction with superoxide at pH 10 were 1.7 x 10(5), 1.5 x
      10(5), and 0.5 x 10(5) M-1 s-1, respectively). At the same time rutin and
      quercetin but not dihydroquercetin are iron ion chelators. These substances were
      used to elucidate the role of radical scavenging and iron chelating in flavonoid
      protection against asbestos-induced oxidative cellular injury. Exposure of rat
      peritoneal macrophages to chrysotile asbestos fibers resulted in "frustrated"
      phagocytosis, cell injury, and a LDH release. Quercetin, dihydroquercetin, and
      rutin were effective in protecting the phagocytic cells against injury caused by
      asbestos. Moreover, these flavonoids exhibited cellular protection in the same
      order of effectiveness as that observed for the quenching of superoxide:
      quercetin > dihydroquercetin > rutin. Exposure of human red blood cells to
      asbestos fibers also caused progressive cell injury and lysis. Quercetin and
      rutin protected the red cells (quercetin > rutin), whereas dihydroquercetin was
      ineffective in preventing asbestos-induced hemolysis. The protective ability of
      quercetin and rutin may be related to their iron-chelating activity. Due to this
      these flavonoids can be located on asbestos surface in sites of initiation of
      free radical reactions and their antiradical moieties can scavenge reactive
      oxygen species immediately after the appearance. Thus, both antiradical and
      chelating effects appear to be involved in the flavonoid protection against
      silica-induced cell injury.

PMID- 9647666
TI  - Purification and characterization of a thermostable class II fumarase from
      Thermus thermophilus.
AB  - A thermostable fumarase was purified from a strain of Thermus thermophilus
      isolated from a Japanese hot spring. The maximum specific activity of the
      purified enzyme was 1740 units/mg at pH 8.0 and 85 degreesC. The enzyme was
      composed of four identical subunits with a molecular weight of 46,000 and
      displayed other enzymatic characteristics which are common to the class II
      fumarases. The thermal stability of the purified enzyme was remarkable, with over
      80% of the activity remaining after a 24-h incubation at 90 degreesC. The enzyme
      was also resistant to chemical denaturants; 50% of the initial specific activity
      was detected in assay mixtures containing 0.8 M guanidine hydrochloride. The
      purified enzyme shared an extremely high sequence homology with Thermus aquaticus
      fumarase and Bacillus subtilis fumarase in the first 43 amino acid residues.

PMID- 9647667
TI  - Studies on the interaction between ferritin and ceruloplasmin.
AB  - We showed previously that ceruloplasmin associates with the H chain of rat liver
      ferritin during iron loading into ferritin such that the iron oxidized by
      ceruloplasmin was deposited into ferritin [S.-H. Juan et al. (1997) Arch.
      Biochem. Biophys. 341, 280-286]. Three synthetic decapeptides derived from
      domains 2, 4, and 6 of ceruloplasmin, referred to CP-2, CP-4, and CP-6, were
      utilized to identify a possible binding site on ceruloplasmin for ferritin. Two
      of the peptides, CP-4 and CP-6, were found to inhibit iron loading into the
      recombinant ferritin H chain homopolymer (rH-Ft) by ceruloplasmin. The extent of
      inhibition of iron loading into ferritin by ceruloplasmin by CP-6, but not CP-4,
      varied with pH, whereas the inhibitory effect remained constant in increasing
      concentrations of NaCl. The addition of rH-Ft quenched the fluorescence emission
      of CP-4 and CP-6, but not CP-2. The quenching of fluorescence was used to
      estimate dissociation constants for the peptides. Iron loading into ferritin in
      Hepes buffer was not affected in the presence of these peptides. In addition,
      synthetic peptides corresponding to the BC loop of ferritin H and L chains were
      utilized to localize an interaction site on ferritin for ceruloplasmin. The BC
      loop of H chain but not L chain of ferritin stimulated the ferroxidase activity
      of ceruloplasmin. Only the BC loop of ferritin H chain decreased the amount of
      iron loading into ferritin by ceruloplasmin.

PMID- 9647668
TI  - Properties of the novel intermediate filament protein synemin and its
      identification in mammalian muscle.
AB  - We examined specific properties of highly purified synemin (230 kDa), recently
      identified as a novel intermediate filament (IF) protein, from avian smooth
      muscle. Soluble synemin in 10 mM Tris-HCl, pH 8.5, appears as approximately 11-nm
      diameter globular structures by negative-stain and low-angle shadow electron
      microscopy. Chemical crosslinking and SDS-PAGE analysis indicate that soluble
      synemin molecules contain two 230-kDa subunits. The pH- and ionic strength
      dependent solubility properties of synemin are similar to those of the type III
      IF protein desmin, but under physiological-like conditions in which desmin self
      assembles into long approximately 10-nm-diameter IFs, synemin self-associates
      into complex, approx 15- to 25-nm-diameter globular structures. Calpain digestion
      demonstrated that synemin is extremely proteolytically labile. Western blot
      analysis, with monospecific polyclonal antibodies against avian synemin, shows
      the presence of the reactive 230-kDa synemin band in samples of adult avian
      skeletal, cardiac, and smooth muscle and of two reactive bands at approximately
      225 kDa (major) and approximately 195 kDa in adult porcine skeletal, cardiac, and
      smooth muscle. Partial purification of synemin from porcine smooth muscle also
      resulted in fractions highly enriched in the approximately 225- and approximately
      195-kDa polypeptides. Conventional immunofluorescence and immunoconfocal
      microscopy of isolated myofibrils and of frozen sections also demonstrated, for
      the first time, that synemin is present in all three adult porcine muscle cell
      types and is colocalized with desmin in skeletal and cardiac muscle cells at the
      myofibrillar Z-lines.

PMID- 9647669
TI  - Inhibition of 25-hydroxyvitamin D3 production by 1, 25-dihydroxyvitamin D3 in
      rats.
AB  - The regulation of the hepatic vitamin D3 25-hydroxylase enzyme system by 1,25
      dihydroxyvitamin D3 was examined using male rats. Circulating 25-hydroxyvitamin
      D3 levels decreased in response to increasing doses of 1,25-dihydroxyvitamin D3
      as determined by HPLC and serum protein binding assay. A maximum reduction in
      serum 25-hydroxyvitamin D3 of 57.7% was achieved by the administration of 1,25
      dihydroxyvitamin D3 and higher doses produced no further reduction. The in vitro
      rate of vitamin D 25-hydroxylation by liver homogenates from rats given 1,25
      dihydroxyvitamin D3 was also reduced by 60.4%. Whole rat extracts from animals
      given [3H]vitamin D3 contained 50.4% less 25-[3H]hydroxyvitamin D3 in treated
      rats given 1,25-dihydroxyvitamin D3 than in those given only the vehicle.
      Further, 1,25-dihydroxyvitamin D3 treatment had no effect on in vivo
      disappearance of 25-[3H]hydroxyvitamin D3. Taken together, these results
      demonstrate that the decrease in 25-hydroxyvitamin D3 levels observed in 1,25
      dihydroxyvitamin D3-treated rats results from a decrease in production and not an
      increase in the metabolic clearance of 25-[3H]hydroxyvitamin D3.

PMID- 9647670
TI  - Massive production of farnesol-derived dicarboxylic acids in mice treated with
      the squalene synthase inhibitor zaragozic acid A.
AB  - The zaragozic acids are potent inhibitors of squalene synthase. In vivo studies
      in mice confirmed our earlier observations that inhibition of squalene synthase
      by zaragozic acid A was accompanied by an increase in the incorporation of label
      from [3H]mevalonate into farnesyl-diphosphate (FPP)-derived isoprenoic acids (J.
      D. Bergstrom et al., 1993, Proc. Natl. Acad. Sci. USA 90, 80-84). Farnesyl
      diphosphate-derived metabolites appear transiently in the liver. We were unable
      to detect any farnesol formation in the zaragozic acid-treated animals which
      indicates that FPP is readily converted to farnesoic acid and dicarboxylic acids
      in the liver. These metabolites were found to be produced only in the liver and
      not in the kidney. trans-3,7-Dimethyl-2-octaen-1,8-dioic acid and 3, 7
      dimethyloctan-1,8-dioic acid were identified as the major end products of
      farnesyl-diphosphate metabolism in the urine of mice treated with zaragozic acid
      A. Quantitative analysis of these FPP-derived dicarboxylic acids by gas-liquid
      chromatography revealed that approximately 11 mg of total dicarboxylic acids is
      excreted per day into the urine of a mouse after 3 days of treatment with
      zaragozic acid A.

PMID- 9647671
TI  - Inhibition by butylmalonate of proton influx in nonphosphorylating mitochondria.
AB  - The impermeability of the inner membrane to protons is one of the four postulates
      of the chemiosmotic theory on the coupling mechanism between respiration and
      phosphorylation in mitochondria. However, oxygen uptake in isolated
      nonphosphorylating mitochondria requires that protons translocated from inside to
      outside must be, at least in part, retaken up. The nonohmic relationship between
      the respiration rate and the protonmotive force has been mainly ascribed to an
      increase in the proton conductance of the inner membrane (proton leak). In liver
      mitochondria oxygen pulse experiments the rate of both the efflux and the reentry
      of protons, linked to the oxygen consumption supported by succinate oxidation, is
      greatly stimulated by low concentrations of butylmalonate. The steady-state level
      of protons exported outside in the acidification-alkalinization cycle of the
      medium, generated by an oxygen pulse, is also increased but the rate of oxygen
      uptake is unaffected. However, in valinomycin-stimulated respiration
      butylmalonate inhibits the ratio of proton influx/oxygen consumption by 50% and
      also stimulates the ratio of proton efflux/oxygen consumption by 50%. Titration
      of the butylmalonate effect gives a saturation curve with a half-maximal effect
      at 5 microM. Identical results are obtained inthe presence of oligomycin which
      excludes the involvement of the ATP-synthase complex. The data obtained are not
      in contrast with the existence in the inner membrane of a channel-like system
      inhibited by butylmalonate and involved, together with other systems, in
      promoting the backflow of protons in nonphosphorylating state 4 respiration. Such
      a system, similar to thermogenin, could be involved in tissues, other than
      adipose, in a more general thermogenesis program by promoting the dissipation as
      heat of the energy given by the electrochemical proton gradient. The possibility
      that butylmalonate might inhibit the proton movement associated with cation and
      anion transport in mitochondria has also been considered.

PMID- 9647672
TI  - Contribution of basic residues of the D and H helices in heparin binding to
      protein C inhibitor.
AB  - Protein C inhibitor (PCI) is a heparin-binding serine protease inhibitor (serpin)
      that regulates hemostatic proteases such as activated protein C (APC) and
      thrombin. The work described here provides further evidence that the PCI H helix,
      but not the D helix, has a major role in heparin-accelerated inhibition of APC
      and thrombin. We previously identified Arg-269 and Lys-270 of the H helix
      [R269A/K270A "H1" recombinant PCI (rPCI)] as important residues both for heparin
      accelerated inhibition of thrombin and APC and for heparin-Sepharose binding
      (Shirk, R. A., Elisen, M. G. L. M., Meijers, J. C. M., and Church, F. C. (1994)
      J. Biol. Chem. 269, 28690-28695). H1 rPCI was used as a template for Ala-scanning
      mutagenesis of other H helix basic residues (H1-K266A, H1-K273A, and H1
      K266A/K273A) and of the D helix basic residues (H1-K82A, H1-K86A, H1-R90A, and H1
      K82A/K86A/R90A). Compared to wild-type rPCI/heparin (k2 = 2.2 x 10(7) M-1 min-1
      for thrombin), heparin-accelerated thrombin inhibition was decreased 2.4-fold by
      H1 rPCI, 4.4-fold by H1-K266A rPCI, and 8-fold by H1-K273A rPCI. H1-K266A/K273A
      rPCI thrombin inhibition was essentially not accelerated by heparin. A similar
      trend was found for APC-heparin inhibition using these H helix rPCI mutants. In
      contrast, the D helix rPCI mutants did not have further reduced heparin
      stimulated thrombin or APC inhibition compared to H1 rPCI. Interestingly, all of
      the H and D helix rPCI mutants had reduced heparin-Sepharose binding activity
      (ranging from 180 to 360 mM NaCl) compared to wild-type rPCI and H1 rPCI, which
      eluted at 650 and 430 mM NaCl, respectively. These data suggest that all four
      basic residues (Lys-266, Arg-269, Lys-270, Lys-273) in the H helix of PCI form a
      heparin binding site. Our results also imply that while the D helix basic
      residues (Lys-80, Lys-86, and Arg-90) contribute to overall heparin binding, they
      are not necessary for heparin-accelerated activity. We conclude that the primary
      heparin binding site of PCI is the H helix and not the D helix as found in other
      homologous heparin-binding serpins such as antithrombin III, heparin cofactor II,
      and protease nexin 1.

PMID- 9647673
TI  - Mechanism-based inhibition of human folylpolyglutamate synthetase: design,
      synthesis, and biochemical characterization of a phosphapeptide mimic of the
      tetrahedral intermediate.
AB  - Folylpolyglutamate synthetase (FPGS) catalyzes anATP-dependent ligation reaction
      that results in the synthesis of poly(gamma-glutamate) metabolites of folates and
      some antifolates. We have synthesized and characterized the prototype of a new
      class of mechanism-based FPGS inhibitor in which a phosphonate moiety mimics the
      tetrahedral intermediate formed during the ligation reaction. This phosphonate, 4
      amino-4-deoxy-10-methyl-pteroyl-L-glutamyl-gamma-[Psi?P(O)(OH)-O?] glutarate (4
      NH2-10-CH3-Pte-L-Glu-gamma-[Psi?P(O)(OH)-O?]glutarate), is not a substrate for
      human FPGS, but is a linear, competitive inhibitor (Kis = 46 nM) with respect to
      methotrexate as the variable substrate. Inhibition is not time-dependent and
      preincubation of FPGS with this phosphonate does not increase the degree of
      inhibition, suggesting that it is not a slow, tight-binding inhibitor involving a
      time-dependent isomerization, EI --> EI*. Substructures containing the
      phosphonate moiety but lacking the pterin are much less inhibitory to FPGS,
      indicating that a significant portion of the inhibitor binding energy is derived
      from the pterin moiety, a feature also observed in substrate binding. 4-NH2-10
      CH3-Pte-L-Glu-gamma-[Psi?P(O)(OH)-O?]glutarate is also an analog of a proposed
      tetrahedral intermediate in the reaction catalyzed by gamma-glutamyl hydrolase
      (gamma-GH), another enzyme of importance in controlling folate homeostasis in
      cells. This intermediate would arise from direct attack of H2O on the dipeptide,
      4-NH2-10-CH3-Pte-L-Glu-gamma-L-Glu. The fact that 4-NH2-10-CH3-Pte-L-Glu-gamma
      [Psi?P(O)(OH)-O?]glutarate is not an inhibitor of gamma-GH strongly suggests that
      hydrolysis of poly-gamma-glutamates catalyzed by gamma-GH does not involve the
      direct attack of water at the scissile amide bond. Methotrexate, its gamma
      glutamyl dipeptide metabolite, and 4-NH2-10-CH3-Pte-L-Glu-gamma-[Psi?P(O)(OH)
      O?]glutarate are equipotent as inhibitors of human dihydrofolate reductase (the
      primary target of methotrexate), but the phosphonate does not significantly
      inhibit another important folate-dependent enzyme, thymidylate synthase. Thus,
      the phosphonate moiety in this analog represents an important new lead in the
      development of FPGS inhibitors.

PMID- 9647674
TI  - Carbohydrate gluing is a strategy for supramolecular clamping of submultiples in
      annelid extracellular multi-subunit hemoglobin.
AB  - A key to understanding the mysterious hierarchic organization of annelid multi
      subunit extracellular hemoglobin (giant Hb, composed of 144 globin chains and
      about 36 nonheme chains called linkers) is knowing the role of linkers in holding
      together the entire two-tiered hexagonal form. Here, the effects of added
      monosaccharides on the dissociation of giant Hb from the marineworm Perinereis
      aibuhitensis were monitored using dynamic light scattering (DLS), transmission
      electron microscopy (TEM), and circular dichroism (CD) measurements. Changes in
      Stokes radius and more clearly the distribution analysis of the Hb based on the
      DLS measurements showed that Hb preferentially dissociates into hexagonal units
      (called submultiples), which was consistent with the results of TEM and CD
      measurements. The results thus show that linkers specifically "clamp"
      submultiples together to organize the two-tiered form through carbohydrate
      gluing. Thus, a submultiple behaves like an ordinary protein, whereas the intact
      Hb behaves like a miniature supramolecular system. This clamp model is plausible
      because it inherently involves catastrophe of the molecular stoichiometry at the
      two-tiered hexagonal formation level because carbohydrates are under
      posttranslational regulation and therefore contain structural ambiguity.

PMID- 9647677
TI  - What is line bisection in unilateral spatial neglect? Analysis of perceptual and
      motor aspects in line bisection tasks.
AB  - Three patients with unilateral spatial neglect could detect the difference of
      length between the right and left segments when a line had a transection mark. To
      examine the effect of response mode, the manual line bisection task and a new
      "line bisection task by fixation" were given to the patients. In tasks that used
      lines with no landmark, they showed apparent rightward errors. The results
      suggest that line bisection is not a task that examines the ability of patients
      with neglect to compare the right and left extents of a line. Where to fixate as
      the subjective midpoint may determine the rightward errors of bisection, whether
      manual response is used or not.

PMID- 9647675
TI  - Cyclic peptides as probes of the substrate binding site of the cytosolic tyrosine
      kinase, pp60c-src.
AB  - A series of 48 cyclic peptides based on the amino acid sequence surrounding the
      autophosphorylation site of pp60(c-src) was synthesized and each was tested as
      both a substrate and an inhibitor of this protein tyrosine kinase. Starting with
      cyclo(Asp1-Asn2-Gln3-Tyr4-Ala5-Ala6-Arg7-Gln8-d- Phe9-Pro10) a six-amino-acid
      survey was performed at positions 1 through 8 to determine which positions were
      critical for affinity and phosphorylation and which amino acids produced the
      greatest activity. Our survey found that Arg7 was detrimental for binding and
      phosphorylation and that aromatic residues were preferred at this position.
      Further increases in affinity were obtained with hydrophobic residues at position
      6 with the optimum for both affinity and phosphorylation being Phe. Changes on
      the "amino-terminal" side of Tyr4 resulted in reduced Vmax values, illustrating
      the requirement for acidic residues in peptidic tyrosine kinase substrates. The
      result of the survey was cyclo(Asp1-Asn2-Gln3-Tyr4-Ala5-Phe6-Phe7-Gln8-d-Phe 9
      Pro10). The change of residues 6 and 7 resulted in a 42-fold increase in affinity
      and no increase in Vmax. As a substrate, this peptide displayed Michaelis-Menten
      kinetics at saturating ATP conditions. As an inhibitor, mixed inhibition was
      observed. A linear version of this peptide was 13-fold less potent an inhibitor
      than the cyclic peptide.

PMID- 9647678
TI  - Relationships among multiple task asymmetries. I. A critical review.
AB  - Previous multiple-task experiments examining relationships among lateral
      difference measures have been interpreted as supporting (a) both global and local
      relationships or (b) local relationships only. The evidence from principle
      components, correlational, and factor analytic approaches is reviewed with the
      aim of reconciling the literature. Although a principle component has been
      reported to which all asymmetries correlate positively, it may not reflect
      existing null and negative correlations between pairs of measures. All three
      literatures make clear that such correlations exist, calling into question the
      reality of a global relationship. In contrast, all three approaches find evidence
      supporting the reality of local relationships. Factor analytic approaches most
      fully develop local relationships and permit interpretation in terms of
      hemispheric processes, but they need to (a) use larger sample sizes, (b)
      prescreen measures for reliability, and (c) make publicly available the
      underlying correlational matrices.

PMID- 9647679
TI  - Relationships among multiple task asymmetries. II. A large-sample factor
      analysis.
AB  - Samples from published and unpublished factor analytic studies of multiple task
      asymmetry are combined to produce a large-sample factor analysis of 10 measures,
      prescreened for significant asymmetry and acceptable reliability, from 9
      lateralized tasks. A full correlational matrix is presented, with task pairings
      having sample sizes ranging from 103 to 479 (mean N = 290). Both significant
      positive and significant negative correlations between measures are found.
      Extraction and oblique rotation of five factors fails to reveal any evidence of a
      global relationship among lateral difference measures, and principal-components
      analysis likewise fails to reveal a component to which all measures correlate
      positively. However, evidence for local structure is found. Results are
      interpreted in terms of dissociable hemispheric processes, and consideration is
      given of the possible existence of modality-specific characteristic perceptual
      asymmetry and of single versus multiple determination of lateral differences.

PMID- 9647680
TI  - The representation of arithmetic facts in memory: results from retraining a brain
      damaged patient.
AB  - This single case study was designed to gather evidence regarding whether the
      mental representations mediating multiplication fact retrieval make use of single
      or multiple codes. MC is a brain-damaged volunteer whose numerical processing
      impairments were limited to multiplication fact retrieval. He relearned three
      sets of multiplication facts. Each set was relearned in one of three input
      formats: Arabic, written verbal, or spoken verbal. Following training all facts
      were tested in all input formats. MC's posttraining performance was virtually
      error free and showed no effects of input format. However, reaction-time data
      showed fact retrieval was fastest when the training format matched the test
      format. Results are discussed in relation to single- and multiple-code models of
      multiplication fact retrieval.

PMID- 9647681
TI  - A twin and family study of the association between immune system dysfunction and
      dyslexia using blood serum immunoassay and survey data.
AB  - We conducted a study of the association between developmental reading disability
      (DRD) and immune disorders (ID) using both survey and immunoassay data in two
      separate samples of families. One sample was made up of twins and their parents
      and was ascertained through a population-based sampling scheme. The other sample
      was a set of extended pedigrees selected for apparent autosomal dominant
      transmission of DRD. We failed to find an association between DRD and ID in
      either sample, regardless of the method used to assess immune system function.
      Even though our twin sample provided evidence that both DRD and immune conditions
      were significantly heritable, there was no evidence for a genetic correlation
      between ID and DRD nor was there any clear indication that a special subgroup of
      individuals may be comorbid for these conditions because of genetic reasons. How
      these negative findings can be reconciled with the developmental hypothesis of
      Geschwind, Behan, Galaburda, and colleagues, and how they may relate to the gene
      locus influencing DRD that has been recently located in the HLA region of the
      short arm of chromosome 6 is discussed.

PMID- 9647682
TI  - Sex differences in object location memory.
AB  - The ability to remember where objects were is thought to require multiple
      separate processes. One has to encode the precise positions occupied, assign the
      various objects to the correct (relative) locations, and achieve an integration
      of both types of spatial information. This study examined whether sex differences
      exist for these selective components of object location memory. Twenty males and
      20 females participated in the following task. On a PC screen, they were shown a
      square with 10 different objects for 30 s. Subsequently, the objects disappeared
      from the screen, reappeared in a row above the square, and subjects were asked to
      relocate them in three different conditions. In the object-to-position-assignment
      condition, the original positions were premarked in the square, so subjects
      needed only to assign the correct object to the correct position. In the
      positions-only condition, all objects assumed the same identity. Therefore,
      subjects had only to reproduce the precise positions. Finally, in the combined
      condition, subjects were required to replace all the different objects in the
      square without any of object positions premarked. The absolute displacements
      between an object's original and its relocated position reflect the integration
      mechanism. Females did as well as males in the object-to-position-assignment
      condition and on the absolute displacements in the combined condition, but they
      were less efficient than males in positional reconstruction per se. Thus, it
      seems that the male advantage in spatial memory is not a general effect but
      applies only to certain specific processing components. Moreover, the employment
      of a dual task during encoding, concurrent articulatory suppression, yielded no
      significant interactions with sex. This suggests that females' weaker positional
      encoding does not derive from the use of an inefficient verbal strategy.

PMID- 9647683
TI  - Stimulus characteristics determine processing approach on random array letter
      cancellation tasks.
AB  - Target-to-distractor ratio strongly influences performance on typical random
      array letter cancellation tasks, suggesting that a "controlled" processing
      approach is used. This study was designed to determine whether "automatic"
      processing could be also demonstrated in the random array cancellation paradigm
      by changing the perceptual characteristics of the stimuli. Thirty-two healthy
      subjects sequentially performed four random array cancellation tasks with 50 and
      100 stimuli. The letters "I" or "O" were targets and "L" served as the
      distractor. Performance was measured by the number of correctly canceled targets
      divided by the time to completion, corrected for accuracy. There was a strong
      effect of the number of stimuli on forms using I targets (p < .00001), but not
      for O's (p = . 15) Performance scores were lower for I target forms than for O
      targets. These findings demonstrate that performance approximating "automatic"
      processing can also be elicited on clinically useful, office-based, or bedside
      tests such as random array cancellation.

PMID- 9647684
TI  - The relation of ERP components to complex memory processing.
AB  - The relation between various ERP components generated during encoding of a word
      and its subsequent recall were investigated using a "rote" serial-order and an
      "elaborative" category memory task. Words (flashed separately) were time-locked
      to EEG recordings from 21 cortical sites. ERP components from the five subjects
      having the highest recall scores were compared to the five lowest scoring
      subjects. Results based on the P200 peak amplitude data as well as the N400 and
      late positive component peak amplitude and latency data suggest that anterior and
      posterior distributional differences are elicited during encoding of words for
      rote and elaborative memory tasks. Furthermore, strong individual differences in
      these patterns were found as a function of task. A tentative argument was made
      that the obtained anterior and posterior differences may index different word
      feature selection and encoding processes, which are differentially utilized by
      high and low recallers.

PMID- 9647686
TI  - Source monitoring: ERP evidence for greater reactivity to nontarget information
      in older adults.
AB  - Event-Related Potentials (ERPs) were collected concurrently with stimulus
      presentation during a source monitoring task. Younger adults were less likely
      than older adults to make source monitoring errors and their ERP records showed
      far greater discrimination between target stimuli and familiar but nontarget
      foils. Older adults not only made more source errors but produced high amplitude
      late positivities to the nontarget foils even when these foils were correctly
      rejected. Under divided attention conditions, younger adults performance was
      similar to that of the older adults both behaviorally and electrophysiologically.
      These data illustrate the role that attentional resources play in the ability to
      inhibit response tendencies and suggest that age differences in source monitoring
      may be more related to attentional control than inefficiencies in the encoding of
      contextual information. As well, they suggest that the ERP late positivity may
      represent a more general response to item salience rather than serve as an index
      of recollection as is the current view.

PMID- 9647685
TI  - Sex differences in right hemisphere tasks.
AB  - We tested the hypothesis that sex differences in spatial ability and emotional
      perception are due to sex differences in intrahemispheric organization of the
      right hemisphere. If the right hemisphere is differently organized by sex
      primarily specialized for spatial ability in men, but primarily specialized for
      emotional perception in women-then there should be a negative correlation between
      spatial ability and emotional perception within sex, and the greatest disparity
      between abilities should be found in people with characteristic arousal of the
      right hemisphere. Undergraduate men (N = 86) and women (N = 132) completed tests
      of Mental Rotation, Surface Development, Profile of Nonverbal Sensitivity,
      Progressive Matrices, and Chimeric Faces. Although the expected pattern of sex
      differences was observed, there was no evidence for the hypothesized negative
      correlation between spatial ability and emotional perception, even after
      statistical control of general intelligence.

PMID- 9647687
TI  - Volume 35, no. 3 (1997) in the poster paper (Article no. BR970966), "26 
AB  - Copyright

PMID- 9647689
TI  - Incorporation and glial differentiation of mouse EGF-responsive neural progenitor
      cells after transplantation into the embryonic rat brain.
AB  - In vitro, epidermal growth factor (EGF)-responsive neural progenitor cells
      exhibit multipotent properties and can differentiate into both neurons and glia.
      Using an in utero xenotransplantation approach we examined the developmental
      potential of EGF-responsive cells derived from E14 mouse ganglionic eminences,
      cortical primordium, and ventral mesencephalon, after injection into the E15 rat
      forebrain ventricle. Cell cultures were established from control mice or from
      mice carrying the lacZ transgene under control of the promoters for nestin, glial
      fibrillary acidic protein (GFAP), or myelin basic protein (MBP). The grafted
      cells, visualized with mouse-specific markers or staining for the reporter gene
      product, displayed widespread incorporation into distinct forebrain and midbrain
      structures and differentiated predominantly into glial cells. The patterns of
      incorporation of cells from all three regions were very similar without
      preference for the homotopic brain areas. These results suggest that EGF
      responsive progenitor cells can respond to host derived environmental cues,
      differentiate into cells with glial-like features, and become integrated in the
      developing recipient brain.

PMID- 9647690
TI  - GFRalpha-4, a new GDNF family receptor.
AB  - GFRalpha-1, GFRalpha-2, and GFRalpha-3 constitute a family of structurally
      related, glycosyl-phosphatidylinosital-linked, cell surface proteins, two of
      which, GFRalpha-1 and GFRalpha-2, are components of the receptor complex for the
      neurotrophic factors GDNF and neurturin, respectively. By screening an embryonic
      chicken brain cDNA library with a GFRalpha-1 probe at low stringency, we isolated
      cDNAs encoding an additional member of the GFRalpha family, GFRalpha-4. The
      nucleotide sequence predicts a 431-amino-acid secreted protein that is more
      closely related to GFRalpha-1 and GFRalpha-2 than to GFRalpha-3. GFRalpha-4 mRNA
      is expressed in distinctive patterns in the brain and several other organs and
      tissues of the chicken embryo. Our findings extend the family of GFRalpha
      proteins and provide information about the tissues in which GFRalpha-4 may
      function during development.

PMID- 9647691
TI  - Search for a nuclear localization signal in the prion protein.
AB  - Spongiform transmissible encephalopathies are neurodegenerative diseases
      characterized by the accumulation, in infected brains, of a pathological form of
      a normal host-encoded protein called PrP. Previous data have shown that PrP could
      interact with cytosolic factors, including nuclear molecules, emphasizing the
      possible function of such interactions. Moreover, in infected cells, PrP is
      observed not only at the plasma membrane but also in the nuclear compartment. The
      N-terminal extremity of the mature PrP has been thought to harbor a nuclear
      localization signal reminiscent of the nuclear localization signal of the simian
      virus 40 large T antigen. By designing a fusion protein between the putative
      nuclear localization signal of PrP and the green fluorescent protein, we have
      shown that the N-terminal sequence of PrP is not efficient in targeting the
      protein in the nuclear compartment. This implies new insights regarding the way
      by which PrP could, however, reach the nuclear compartment.

PMID- 9647692
TI  - Parallel molecular genetic pathways operate during CNS metamorphosis in
      Drosophila.
AB  - Insect metamorphosis provides a valuable model for studying mechanisms of steroid
      hormone action on the nervous system during a dynamic phase of functional
      remodeling. The Drosophila Broad Complex (BRC) holds a pivotal position in the
      gene expression cascade triggered by the molting hormone 20-hydroxyecdysone (20E)
      at the onset of metamorphosis. We previously demonstrated that the BRC, which
      encodes a family of zinc-finger transcription factors, is essential for
      transducing 20E signals into the morphogenetic movements and cellular assembly
      that alter the CNS from juvenile to adult form and function. We set out to
      examine the relationship of BRC to two other genes, IMP-E1 and Deformed (Dfd),
      involved in the metamorphic transition of the CNS. Representatives of the whole
      family of BRC transcript isoforms accumulate in the CNS during the larval-to
      pupal transition and respond directly to 20E in vitro. IMP-E1 is also directly
      regulated by 20E, but its induction is independent of BRC, revealing that 20E
      works through at least two pathways in the CNS. DFD expression is also
      independent of BRC function. Surprisingly, BRC and DFD proteins are expressed in
      distinct, nonoverlapping subsets of neuronal nuclei of the subesophageal ganglion
      even though both are required for its migration into the head capsule. This
      suggests that the segment identity and ecdysone cascades operate in parallel to
      control region-specific reorganization during metamorphosis.

PMID- 9647693
TI  - Atrophin-1, the DRPLA gene product, interacts with two families of WW domain
      containing proteins.
AB  - Atrophin-1 contains a polyglutamine repeat, expansion of which is responsible for
      dentatorubral and pallidoluysian atrophy (DRPLA). The normal function of atrophin
      1 is unknown. We have identified five atrophin-1 interacting proteins (AIPs)
      which bind to atrophin-1 in the vicinity of the polyglutamine tract using the
      yeast two-hybrid system. Four of the interactions were confirmed using in vitro
      binding assays. All five interactors contained multiple WW domains. Two are
      novel. The AIPs can be divided into two distinct classes. AIP1 and AIP3/WWP3 are
      MAGUK-like multidomain proteins containing a number of protein-protein
      interaction modules, namely a guanylate kinase-like region, two WW domains, and
      multiple PDZ domains. AIP2/WWP2, AIP4, and AIP5/WWP1 are highly homologous, each
      having four WW domains and a HECT domain characteristic of ubiquitin ligases.
      These interactors are similar to recently isolated huntingtin-interacting
      proteins, suggesting possible commonality of function between two proteins
      responsible for very similar diseases.

PMID- 9647694
TI  - CIPP, a novel multivalent PDZ domain protein, selectively interacts with Kir4.0
      family members, NMDA receptor subunits, neurexins, and neuroligins.
AB  - We report a novel multivalent PDZ domain protein, CIPP (for channel-interacting
      PDZ domain protein), which is expressed exclusively in brain and kidney. Within
      the brain, the highest CIPP mRNA levels were found in neurons of the cerebellum,
      inferior colliculus, vestibular nucleus, facial nucleus, and thalamus.
      Furthermore, we identified the inward rectifier K+ (Kir) channel, Kir4.1 (also
      called "Kir1.2"), as a cellular CIPP ligand. Among several other Kir channels
      tested, only the closely related Kir4.2 (or "Kir1.3") also interacted with CIPP.
      In addition, specific PDZ domains within CIPP associated selectively with the C
      termini of N-methyl-D-aspartate subtypes of glutamate receptors, as well as
      neurexins and neuroligins, cell surface molecules enriched in synaptic membranes.
      Thus, CIPP may serve as a scaffold that brings structurally diverse but
      functionally connected proteins into close proximity at the synapse. The
      functional consequences of CIPP expression on Kir4.1 channels were studied using
      whole-cell voltage clamp techniques in Kir4.1 transfected COS-7 cells. On
      average, Kir4.1 current densities were doubled by cotransfection with CIPP.

PMID- 9647695
TI  - Mycosis of bandedwinged whitefly (Trialeurodes abutilonea) (Homoptera:
      aleyrodidae) caused by Orthomyces aleyrodis gen. & sp. nov. (Entomophthorales:
      Entomophthoraceae).
AB  - A new genus and species of fungus, Orthomyces aleyrodis Steinkraus, Humber &
      Oliver gen. & sp. nov. (Entomophthorales: Entomophthoraceae) is described. In
      1994 and 1995, this fungus caused epizootics in high populations of bandedwinged
      whitefly (Trialeurodes abutilonea) on cotton and cocklebur in Alabama. In 1996,
      T. abutilonea populations were lower and no infected specimens were found. This
      is the first report of an entomophthoralean infecting an aleyrodid in the New
      World and the first report of entomophthoralean epizootics in whiteflies.

PMID- 9647696
TI  - Histopathological effects of Bacillus thuringiensis on the alimentary canal of
      the sheep louse, Bovicola ovis.
AB  - Sequential observations were made of the ultrastructural effects of Bacillus
      thuringiensis (Bt) subsp. kurstaki strain WB3S16 on midgut epithelial cells of
      the sheep biting louse, Bovicola ovis, after the lice were fed, ad libitum, a
      powdered preparation of Bt spores, delta-endotoxin crystals, and lysed cellular
      components. Light microscope observations revealed cytopathological changes to
      the midgut epithelial cells 4 h postfeeding. Transmission electron micrographs
      showed that the microvilli of the midgut epithelial cells became disrupted 4-8 h
      postfeeding, after which the cells became vacuolated and swollen, and the cell
      organelles lost definition and disappeared. Paralysis and death of B. ovis
      occurred between 8 and 12 h postfeeding, coincident with midgut cells lysis and
      release of cellular contents into the midgut lumen. The histopathological effects
      reported here are similar to those reported in lepidopteran and coleopteran
      larvae affected by the delta-endotoxin crystal proteins. The constituent
      fractions of the Bt preparation were tested for toxicity to B. ovis using a
      feeding bioassay. Native delta-endotoxin crystals were not toxic to B. ovis and
      remained intact in the midgut of the insect. There was no evidence that the
      native Bt crystal was involved in the cytopathology and death of the lice.
      However, in vitro solubilized delta-endotoxin crystal proteins were significantly
      toxic to B. ovis. In addition, a louse active toxin was associated with the Bt
      membranes and culture supernatant.

PMID- 9647697
TI  - Characterization of isolates of Paenibacillus larvae subsp. larvae from diverse
      geographical origin by the polymerase chain reaction and BOX primers.
AB  - Ninety-nine strains of Paenibacillus larvae subsp. larvae, the causal agent of
      American Foulbrood disease (AFB) of honeybees, were isolated from different
      regions of Argentina and other countries. The isolates were characterized on the
      basis of DNA fingerprints by a polymerase chain reaction technique (PCR) with BOX
      sequence-specific primers. Isolates from Argentina generated three groups of
      patterns (designated A, B, and C), while P. larvae subsp. larvae strains obtained
      from other countries yielded two distinguishable patterns (coincident with A and
      B). Strains from U.S. A. and Germany were identical and related to Group A, while
      all Czech and English isolates belonged to Group B. Strains from France, Poland,
      Italy, Sweden, and New Zealand showed two different patterns (A and B).
      Comparisons of the biochemical type and genotype of isolates rendered no obvious
      linkage between both features. These results suggest that AFB in Argentina
      resulted from multiple sources of contaminated material.

PMID- 9647699
TI  - Infectivity and pathogenicity of Baculovirus penaei (BP) in cultured larval and
      postlarval Pacific white shrimp, Penaeus vannamei, related to the stage of viral
      development.
AB  - The infectivity and pathogenicity of the penaeid shrimp virus, Baculovirus penaei
      (BP), is influenced by the stage of viral development. This study consisted of a
      preliminary experiment which showed that nonocculuded virus administered per os
      is infective, followed by two infectivity experiments. In the first phase of each
      infectivity experiment, mysis stage larvae of Penaeus vannamei were inoculated
      with BP and samples of infected tissue were collected at various times
      postinoculation (p.i.). These samples were then used to inoculate either mysis or
      postlarval stage P. vannamei in the second phase of each experiment. Viral
      inocula prepared from patently infected tissues consistently produced infections
      in both mysis and postlarval stage shrimp. Inocula prepared from prepatently
      infected tissue collected 12-18 h p.i. produced infections in some, but not all
      replicate cultures, while inocula prepared from tissues collected earlier than 12
      h p.i. were not infective. Viral development in mysis stage larvae was
      substantially delayed and the mortality was significantly lower when the viral
      inocula were prepared from prepatently compared to patently infected tissues. BP
      appears to be most pathogenic to larvae that have been exposed to inocula
      prepared from tissues that had recently developed a high prevalence of patent
      infections or about 72 h p.i.

PMID- 9647698
TI  - Identification of a novel Lymantria dispar nucleopolyhedrovirus mutant that
      exhibits abnormal polyhedron formation and virion occlusion.
AB  - In previous studies on the formation of Lymantria dispar nuclear polyhedrosis
      virus (LdMNPV) few polyhedra (FP) mutants, several polyhedron formation mutants
      (PFM) were identified that appeared to be unique. These viral mutants are being
      characterized to investigate the processes of polyhedron formation and virion
      occlusion. LdMNPV isolate PFM-1 is one of these mutants, and is described in this
      report. Genetic techniques were used to determine if isolate PFM-1 contained a
      mutation in the polyhedrin or 25K FP gene. Wild-type viruses were recovered after
      coinfection of Ld652Y cells with isolate PFM-1 and a FP mutant, and with isolates
      PFM-1 and PFM-C (isolate PFM-C contains a mutation in the polyhedrin gene). These
      viruses were analyzed by genomic restriction endonuclease digestion and found to
      be chimeras of the original PFMs used in the coinfections. Marker rescue studies
      mapped the mutation in isolate PFM-1 to a genomic region that does not include
      the polyhedrin or 25K FP genes. Isolate PFM-1 produced approximately 14-fold
      fewer polyhedra than LdMNPV isolate A21-MPV, an isolate that produces wild-type
      levels of polyhedra, and approximately 2-fold more polyhedra compared to the FP
      isolate 122-2. Polyhedra generated by isolate PFM-1 were normal in size and shape
      but contained very few viral nucleocapsids. The same amount of budded virus (BV)
      was released from cells infected with isolates PFM-1 and A21-MPV. In contrast,
      isolate 122-2 yielded significantly more BV than isolates PFM-1 and A21-MPV.

PMID- 9647700
TI  - Chemotactic responses of tunicate (Urochordata, Ascidiacea) hemocytes in vitro.
AB  - A number of molecules were found to alter the motility of tunicate hemocytes.
      Bacterial lipopolysaccharide (LPS) significantly enhanced cell mobility relative
      to non-stimulated controls. Responses to LPS were not directional and so
      represented chemokinesis. In contrast, checkerboard analyses indicated that two
      tunicate hemolymph proteins, tunIL1-alpha and -beta, stimulated truly directional
      chemotaxis by hemocytes. The data suggest that tunIL1 proteins may contribute to
      defense by altering the localization of immunocompetent cells.

PMID- 9647701
TI  - A polydnavirus from the spruce budworm parasitoid, Tranosema rostrale
      (Ichneumonidae).
AB  - The calyx epithelium of the campoplegine wasp, Tranosema rostrale, contains
      typical ichneumonid polydnaviruses (PVs) that display an apparently uncommon
      association with the egg chorion. The latter structure features fine hair-like
      projections, longest around the egg's apices. In the lumen of the ovary, T.
      rostrale virus becomes lodged between these projections and forms a particulate
      coat around the egg. In the host, Choristoneura fumiferana, projections and
      associated virions are observed in close contact with basement membranes of fat
      body and muscle tissues, to which the eggs rapidly become attached following
      introduction into the host hemocoel. We discuss the implications of this unusual
      virus-chorion association in terms of immune protection, delivery of virus to
      specific host tissues, and the evolution of PVs.

PMID- 9647702
TI  - Observations on the presence of the peritrophic membrane in larval Trichoplusia
      ni and its role in limiting baculovirus infection.
AB  - Light microscopical examinations of dissected and stained peritrophic membranes
      (PMs) were conducted to determine the presence or absence of this protective
      structure in larvae of Trichoplusia ni, prior to and through ecdysis.
      Observations of fourth- and fifth-instar larvae of T. ni from two independent
      rearing colonies showed that PMs were present and lined the midgut prior to,
      during, and immediately after ecdysis in both instars. Western blot analysis of
      insect intestinal mucin (IIM), a major protective protein in the T. ni PM,
      indicated that synthesis of IIM occurred during T. ni embryonic development, or
      more precisely, that IIM synthesis started approximately 4 h prior to hatching.
      These results demonstrated that the neonate T. ni midgut is lined with a
      protective mucinous layer at hatching. A baculovirus enhancin from T. ni
      granulosis virus (TnGV) enhanced per os viral infections of budded viruses (BVs)
      of Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) and T. ni
      single nuclear polyhedrosis virus (TnSNPV) in neonate, fourth-, and fifth-instar
      larvae of T. ni. These results provided further evidence that the PM may serve as
      a partial barrier to viruses in the midgut lumen and that enhancins can
      facilitate the infection process.

PMID- 9647703
TI  - AcMNPV pathogenesis and developmental resistance in fifth instar Heliothis
      virescens.
AB  - Autographa californica M nucleopolyhedrovirus carrying a lacZ reporter gene was
      used to study pathogenesis and developmental resistance in fifth instar Heliothis
      virescens. Compared to fourth instar larvae, the progression of infection
      proceeded much more slowly in fifth instar larvae, and developmental resistance
      in orally inoculated larvae was much more sudden and severe. The resistance
      occurred within the first 6 h of the fifth instar and was partially relieved by
      the optical brightener M2R. Inclusion of M2R in oral inocula not only increased
      mortality levels, but also increased both the percentages of insects expressing
      lacZ and the numbers of foci 24 h after infection. This early developmental
      resistance was not observed in insects infected intrahemocoelically, indicating
      that it was mediated by the midgut and/or the tracheal system servicing the
      midgut. Another less severe resistance was encountered in insects
      intrahemocoelically infected 36 to 48 h postmolt. This later resistance was
      partially relieved by methoprene indicating that it was, in part, hormonally
      mediated. Fifth instar insects fatally infected prior to 12 h postmolt never
      pupated, but pupation increasingly occurred in insects fatally infected 12 to 48
      h postmolt. This pattern of larval/pupal death was consistent with viral
      inactivation of the ecdysone commitment peak.

PMID- 9647704
TI  - Processing of delta-endotoxin of Bacillus thuringiensis subsp. kurstaki HD-1 in
      Heliothis armigera midgut juice and the effects of protease inhibitors.
AB  - Bombyx mori was found to be more sensitive to the protoxins of HD-1 than
      Heliothis armigera. SDS-PAGE analysis showed that a large amount of activated
      toxin was yielded from protoxin by B. mori gut juice while little was yielded by
      H. armigera. Further degradation of activated toxin was observed in H. armigera
      midgut juice detected by SDS-PAGE. pH influenced the proteolytic activity of the
      midgut juice significantly, but there was no obvious effect of pH on the
      degradation of activated toxin. Specific inhibitor study revealed the presence of
      trypsin, chymotrypsin, and elastase in the midgut juice. TLCK, TPCK, elastatinal
      and some general serine protease inhibitors successfully prevented the excessive
      degradation of protoxin in H. armigera midgut juice. Chymotrypsin inhibitors
      showed strong inhibitory effects against the further degradation of activated
      toxin, indicating that chymotrypsin played a major role in the process. It was
      presumed that the excessive degradation of protoxin in H. armigera midgut juice
      was responsible for the low sensitivity of the insect to Bt. Further study
      demonstrated that the excessive degradation in vitro was triggered by SDS
      treatment. However, all of the tested serine protease inhibitors expressed
      synergism with protoxin against H. armigera larvae, suggesting that the excessive
      degradation of protoxin may occur in vivo to some extent and may be triggered by
      receptor binding of activated toxin.

PMID- 9647705
TI  - Detection of a virus enhancing factor in the spheroid, spindle, and virion of an
      entomopoxvirus.
AB  - Spheroids, spindles, and virions of an entomopoxvirus (EPV) enhanced the
      infectivity of a nuclear polyhedrosis virus (NPV) when they were perorally
      administered to larvae of the armyworm, Pseudaletia separata. Spheroids and
      spindles at the same dose exhibited nearly the same enhancing activity. When the
      dose of spheroids or spindles was reduced 10 times, the median infectious dose of
      the NPV was increased approximately 100 times. An antiserum against an enhancing
      factor detected the homologous antigen in spheroids, spindles, and tissue-derived
      EPV virions but not in spheroid-derived virions.

PMID- 9647706
TI  - A procaryote infecting the black-lipped pearl oyster Pinctada margaritifera.

PMID- 9647707
TI  - In vitro yields and in vivo activity of a polyhedrin gene-deleted and wild strain
      of the nucleopolyhedrosis virus of Autographa californica.

PMID- 9647708
TI  - Characterization of tissue water in Tribolium confusum parasitized by
      metacestodes of Hymenolepis diminuta.

PMID- 9647709
TI  - Absolute Absorption Intensities in the Fundamental nu2 and nu5 Bands of 12CH3F.
AB  - The absolute strengths of 93 lines belonging to the nu2 and nu5 bands of methyl
      fluoride were measured in the range of 1416-1503 cm-1 using a tunable diode-laser
      (TDL) spectrometer. These experimental line intensities were obtained from the
      equivalent width method. The intensities were analyzed within a dyad system,
      required to account properly for the strong Coriolis coupling between nu2 and
      nu5. The fit to the experimental data led to the determination of the dipole
      moment derivatives partial differentialu/ partial differentialq2 and partial
      differentialu/ partial differentialq5, as well as the first-order Herman-Wallis
      correction in K to partial differentialu/ partial differentialq5. The intensities
      were reproduced with an overall standard deviation of 1.44%, to be compared with
      a mean experimental uncertainty equal to 1.58%. The values derived for the
      vibrational band strengths of nu2 and nu5 are 2.124 (18) cm-2.atm-1 and 36.96 cm
      2.atm-1 at 296 K, respectively. Copyright 1998 Academic Press.

PMID- 9647710
TI  - Fourier Transform Infrared Spectroscopy of the First CO-Stretch Overtone Band of
      13CH3OH.
AB  - This paper presents a high-resolution Fourier transform infrared study of the
      first CO-stretch overtone band of 13CH3OH. The spectrum has been recorded at the
      Justus-Liebig University, Giebetasen, Germany on their Bruker IFS 120 HR Fourier
      transform spectrometer. We have assigned parallel subbands in the torsional state
      n = 0 for K values up to 6. Each individual subband has been fitted to a J(J + 1)
      power series expansion in order to obtain the subband origin and the state
      specific energy expansion coefficients for the first CO-stretch overtone state.
      The average rotational constant B in the CO-stretch vCO = 2 state was found to be
      0.768 cm-1, forming a smooth series with that of 0.777 cm-1 obtained in the vCO =
      1 state and the ground state value of 0.787 cm-1. Modeling of the excited state
      torsion-vibration energy level structure derived from the subband origins is then
      discussed and molecular parameters in the vCO = 2 state are proposed. The value
      obtained for the barrier height to internal rotation is 377.06 +/- 0.52 cm-1,
      nearly indistinguishable from the value 378.65 cm-1 reported for the CO-stretch
      vCO = 1 state. The vibrational energy is found to be 2020.9 +/- 1.4 cm-1. The
      harmonic wavenumber for the CO-stretch vibration in 13CH3OH was calculated to be
      omega = 1029.9 cm-1. The anharmonicity constant of this vibration is omegax = 6.5
      cm-1, giving x = 6.3 x 10(-3). We have also observed asymmetry-induced K doubling
      for the subbands of A symmetry for K values from 1 to 3 at sufficiently high J
      values. The size of the splitting coefficients is similar to those observed for
      the CO-stretch fundamental, with the exception of those for the K = 3A doublet,
      where the observed splitting is about 18% larger than that for the ground and CO
      stretch vCO = 1 states. Copyright 1998 Academic Press.

PMID- 9647711
TI  - Infrared Fundamental and First Hot Bands of O12C17O Isotopic Variants of Carbon
      Dioxide.
AB  - Infrared spectra of 16O12C17O, 17O12C17O, and 17O12C18O in a carbon dioxide
      sample enriched with oxygen-17 have been recorded with a resolution of about
      0.0025 cm-1 in the regions of the fundamental bands, nu2 (600-800 cm-1) and nu3
      (2200-2400 cm-1), and in the region of the "forbidden" band, nu1 (1200-1400 cm
      1), using the long path difference Fourier transform spectrometer of the LPMA in
      Paris. For each species, the first hot band in the 4.5-um region and two hot
      bands at least in the 15-um region have been studied for the first time, and a
      simultaneous reduction of wavenumbers measured in different spectral regions has
      been carried out yielding new or improved spectroscopic constants. Line
      intensities have been measured in the region of the nu2 and nu3 bands of
      16O12C17O, and the corresponding rotationless transition dipole moments and
      Herman-Wallis coefficients have been reported. Copyright 1998 Academic Press.

PMID- 9647712
TI  - High-Resolution Study of the Near-Infrared A2Pi1/2-X2Sigma+ Transition of YS.
AB  - A high-resolution excitation spectrum of gaseous YS has been recorded by laser
      excitation spectroscopy in a supersonic molecular beam. The YS molecules were
      produced by the reaction of laser-ablated yttrium atoms with CS2. The band of the
      A 2Pi1/2-X 2Sigma+ transition near 750 nm was rotationally analyzed, and a set of
      molecular constants is given for both electronic states. Copyright 1998 Academic
      Press.

PMID- 9647713
TI  - Dynamically Modified Torsional Eigenstates for Single-Top Molecules.
AB  - We present a semiclassical treatment for the inclusion of kinetic energy
      dependent variations in the moment of inertia for certain molecules exhibiting
      internal rotational motion. The model is applied to trifluoroacetyl bromide and
      the resulting dynamically modified transition energies yield an improved spectral
      deviation in contrast to the rigid model. Copyright 1998 Academic Press.

PMID- 9647714
TI  - Fourier Transform Spectroscopy of 18O-Enriched Carbonyl Sulfide from 1825 to 2700
      cm-1
AB  - We have measured the Fourier transform spectrum of carbonyl sulfide from 1825 to
      2700 cm-1, using a sample enriched in both 18O (94.0%) and 17O (1.54%). A careful
      calibration yields a line-position accuracy between 1.5 and 3.0 10(-5) cm-1. We
      have observed and analyzed 118 infrared bands of which 93 are measured for the
      first time: 55 for 18O12C32S, 20 for 18O12C34S, 11 for 18O12C33S, 1 for
      18O12C36S, 12 for 17O12C32S, 4 for 17O12C34S, 2 for 17O12C33S, and 13 for
      18O13C32S. Intensities are also reported and analyzed for all those bands. The
      intensity accuracy is better than 10%, and the precision of approximately 1%
      allows us to determine some Herman-Wallis coefficients. Copyright 1998 Academic
      Press.

PMID- 9647715
TI  - The B1Pi --> X1Sigma+ System of Scandium Monoiodide.
AB  - Rotational analyses have been carried out on eight thermically excited emission
      bands of the infrared B1Pi --> X1Sigma+ system of scandium monoiodide between
      4000 to 5000 cm-1, recorded by Fourier transform spectrometry. Rotational
      constants and energies are obtained for X1Sigma+ (v = 0, 1, 2) and B1Pi (v = 0-4)
      levels from which equilibrium constants of the states are derived. Perturbational
      effects are observed in the bands with v" = 1 that are interpreted as
      consequences of the avoided crossing of X1Sigma+ (v = 1) and a3Delta1 (v = 0) at
      J = 70. A treatment of the perturbation is made using an effective 2 x 2 matrix
      representation of the rotational energies of the two levels. Copyright 1998
      Academic Press.

PMID- 9647716
TI  - Lamb-Dip Millimeter-Wave and High-Resolution Far Infrared Spectra of HCCF.
AB  - The ground state rotational spectrum of fluoroacetylene was measured in the
      millimeter-wave and FIR regions up to 1280 GHz and J = 65. Very accurate values
      of the rotational and centrifugal distortion constants were determined and in
      particular a more reliable value of H0 = 2.0 10(-4) Hz has been obtained compared
      to that previously determined of -0.30 Hz. HCCF was prepared in a dc glow
      discharge in presence of 1,3,5-trifluorobenzene. Copyright 1998 Academic Press.

PMID- 9647717
TI  - Nuclear Quadrupole Coupling in 1,1,1-Trichloroethane: Inertial and Principal
      Tensors for 35Cl and 37Cl.
AB  - The hyperfine structure in the J = 1 <-- 0 and J = 2 <-- 1 transitions of
      35Cl3CCH3 and 35Cl237ClCCH3 was resolved by utilizing the sub-Doppler resolution
      of a pulsed supersonic beam, cavity Fourier transform microwave (FTMW)
      spectrometer. The complete inertial and principal quadrupole tensors of the
      chlorine nuclei are determined. The symmetric top treatment for 35Cl3CCH3 and the
      asymmetric top treatment for 35Cl237ClCCH3 are found to yield identical results
      for the principal tensor components of the 35Cl nucleus. The quadrupole asymmetry
      parameter eta for the chlorine nuclei in 1,1,1-trichloroethane is small, which
      indicates nearly cylindrical symmetry of the field gradient. Nevertheless, there
      is evidence for some deviation of the z symmetry axis of the field gradient from
      the direction of the C-Cl bond. Copyright 1998 Academic Press.

PMID- 9647718
TI  - High-Resolution Infrared Diode Laser Spectroscopy of Ne-N2O, Kr-N2O, and Xe-N2O.
AB  - The rotationally resolved spectra of the van der Waals complexes Ne-N2O, Kr-N2O,
      and Xe-N2O have been investigated in the region of the nu3 N2O monomer
      vibrational band using a diode laser absorption spectrometer that is incorporated
      with a multipass cell and a pulsed jet. The spectra of these three complexes are
      completely analyzed using a normal asymmetric rotor Hamiltonian, and the
      effective molecular constants are accurately determined for both the ground and
      the excited vibrational states. These results show that, like Ar-N2O, the
      complexes have a T-shaped configuration in which the rare gas atom prefers to lie
      near to the oxygen side of N2O. The band origins of Rg-N2O (Rg = Ne, Ar, Kr, and
      Xe) are observed to shift by 0.36125, 0.15038, -0.10131, and -0.49066 cm-1 from
      that of the monomer, respectively. These band origin shifts are well explained by
      a simple model for the intermolecular potential. Copyright 1998 Academic Press.

PMID- 9647719
TI  - The Molecular Constants and Potential Energy Curve of the Ground State X1Sigma+
      in KLi.
AB  - The ground state X1Sigma+ of the diatomic molecule KLi has been studied by
      analyzing spectra of the B1Pi-X1Sigma+ system, simplified by polarization
      labeling. Rotational and vibrational constants are reported for the X1Sigma+
      state covering about 45% of its potential well depth and the potential curve is
      constructed by the Rydberg-Klein-Rees (RKR) procedure. Comparison with previous
      experimental and theoretical work is made. Copyright 1998 Academic Press.

PMID- 9647720
TI  - Saturation Sideband CO2 Laser Spectroscopy of the Overtone Band 2nu2 and Its Hot
      Band 3nu2-nu2 of Carbonyl Sulfide.
AB  - The saturation spectra of the 2nu2 and the 3nu2-nu2 bands of carbonyl sulfide
      have been studied using a CO2 laser sideband spectrometer. The frequency of 20
      absorption lines has been determined with an accuracy of 20 kHz. These data have
      been included in a global rovibrational analysis including all the other data
      available on 16O12C32S. We list an improved set of standard frequencies at the
      10(-6) cm-1 level. Copyright 1998 Academic Press.

PMID- 9647721
TI  - Observation of TiF+ by Velocity Modulation Laser Spectroscopy and Analysis of the
AB  - The molecular ion TiF+ has been observed for the first time using high-resolution
      spectroscopy. The ions were produced in the positive column of an AC glow
      discharge with a gas mixture of He/TiF4. A single-mode cw dye laser along with
      the velocity modulation detection technique was used to record an absorption
      spectrum in the spectral region 16 800-18 600 cm-1. The observed system was
      assigned to the 0-0 and 1-1 bands of the [17.6]3Delta-X3Phi transition of TiF+.
      The rotational analysis of the main subbands has been performed up to J values
      equal to 77 and 56 for the 0-0 and 1-1 bands, respectively. Despite a careful
      search, no intercombination band was observed. A set of effective molecular
      parameters has been determined, characterizing the v = 0, 1 levels of the
      [17.6]3Delta and X3Phi states. The spin-orbit constants Ae and the vibrational
      constants omegae, omegaexe have been estimated for both electronic states, as
      well as their equilibrium distances Re (1.7509 and 1.7800) A for the [17.6]3Delta
      and X3Phi states, respectively). Copyright 1998 Academic Press.

PMID- 9647722
TI  - Diode Laser and FTIR Spectroscopy of BrCN Isotopomers in the Region of the nu3
      Band.
AB  - The nu3 fundamental band (C-N stretch) and four associated hot bands (01(1)1
      01(1)0, 10(0)1-10(0)0, 02(0)1-02(0)0, and 02(2)1-02(2)0) of natural 79/81Br12C14N
      have been recorded and analyzed in the 4.8-um region using an FTIR spectrometer.
      Analyses of the same hot bands, previously recorded using a diode laser
      spectrometer, are also presented for the 13C and 15N isotopically labeled
      species. Copyright 1998 Academic Press.

PMID- 9647723
TI  - The nu6 + nnu9 Levels of Dicyanoacetylene.
AB  - In addition to the previously observed band system nu6 + (n + 1)nu9-nnu9 with n =
      0 to 7, Deltal = 0, and l = n near 611 cm-1, we have identified the nu6 + (n +
      1)nu9 - (n + 2)nu9 system with n = 0 to 6, Deltal = 0, and l = n + 2 near 397 cm
      1. From these bands the rovibrational levels of the states (v6, nv9) with n < 4
      have been determined and spectroscopic parameters have been obtained taking into
      account rotational and vibrational l-type resonances. Effective anharmonicity
      constants x69 and g69 have been calculated also for levels with n >/= 4.
      Copyright 1998 Academic Press.

PMID- 9647724
TI  - Zeeman Tuning Rates for Q-Branch Transitions in the nu3 Band of NO2
AB  - Zeeman tuning rates have been measured for Q-branch transitions in the nu3 band
      of NO2 ( approximately 1610 cm-1) for magnetic fields of up to 564 Gauss. The
      average measured tuning rate is 0.1815(53) x 10(-3) cm-1/Gauss with no dependence
      on Ka within the approximately 3% standard deviation. Despite significant spin
      rotation interaction between several of the observed levels the result agrees
      with the simple linear model for Hunds case (b) molecules (tuning rate = 2uogs =
      0.18696 x 10(-3) cm-1/G), which neglects the spin-rotation interaction between
      different J states. The Zeeman effect is analyzed in a full treatment of the
      Hamiltonian, including spin-rotation interaction, in order to account for the
      agreement with 2uogs and to explore the onset of spin-rotation effects in the
      spectra as the magnetic field is increased. Copyright 1998 Academic Press.

PMID- 9647725
TI  - Rotational Spectrum of CD2I2
AB  - The rotational spectrum of CD2I2 was measured and analyzed by combining results
      from two different millimeter wave spectrometers. Low-J transitions were measured
      with a free jet spectrometer at conditions of completely resolved hyperfine
      structure over the frequency range 59-69 GHz. High-J rotational transitions were
      measured at room temperature at frequencies 167-338 GHz and for J" up to 190".
      Spectroscopic constants in the sextic rotational Hamiltonian of CD2I2 have been
      determined, and the analysis of the observed hyperfine structure yielded all
      components in the inertial and in the principal nuclear quadrupole coupling
      tensors for the iodine nuclei. The rotational constants for CD2I2 and those for
      CH2I2 from Z. Kisiel, L. Pszczolkowski, W. Caminati, and P. G. Favero (1996. J.
      Chem. Phys. 105, 1778-1785) have been used to evaluate a full r0 structure and
      have been combined with the results of ab initio calculations to also evaluate
      the average r* structure: r(CI) = 2.1364 A, r(CH) = 1.078 A, <(ICI) = 113.83
      degrees, and <(HCH) = 113.3 degrees. The current results complete the first
      analysis of a rotational spectrum of a molecule containing two iodine nuclei.
      Copyright 1998 Academic Press.

PMID- 9647726
TI  - Water Vapor Line Assignments in the Near Infrared.
AB  - The high-resolution spectrum of water vapor between 13 200 and 16 500 cm-1
      recorded by J.-Y. Mandin, J-P. Chevillard, C. Camy-Peyret, J.-M. Flaud, and J. W.
      Brault (1986. J. Molec. Spectrosc., 116, 167) is analyzed using high-accuracy
      linelists obtained using ab initio calculations and spectroscopically determined
      potential. Assignments to H216O transitions are presented for 663 of the 795
      unassigned lines presented in the original paper. In addition, 38 lines are
      reassigned. The majority of these assignments and reassignments are confirmed by
      combination differences. These assignments significantly extend the measured data
      for the 4nu and 4nu + delta polyads and provide the first information on the
      (240), (033), (160), (170), and (071) bands. It is likely that a significant
      fraction of the remaining unassigned lines belong to H218O. Copyright 1998
      Academic Press.

PMID- 9647729
TI  - Molecular biology of the proteasome.
AB  - The proteasome is an unusually large multisubunit proteolytic complex, consisting
      of a central catalytic machine (equivalent to the 20S proteasome) and two
      terminal regulatory subcomplexes, termed PA700 or PA28, that are attached to both
      ends of the central portion in opposite orientations to form the enzymatically
      active proteasome. Totally about 40 subunits with sizes of 20-110 kDa are
      assembled to form two types of the proteasomal complexes with the same catalytic
      core and different regulatory modules. To date, cDNAs or genes encoding almost
      all subunits of human and the budding yeast proteasomes have been isolated by
      molecular-biological techniques. In this minireview, I summarize briefly
      available information on the structure-function relationships of the proteasome
      acting as a protein death machinery.

PMID- 9647730
TI  - Basophilic differentiation of the human leukemia cell line KU812 upon treatment
      with interleukin-4.
AB  - The human leukemia cell line KU812 had been described as an immature
      prebasophilic cell line and exhibits a potential to differentiate into mature
      basophils. We studied the effect of interleukin-4 (IL-4) on the basophilic
      differentiation of KU812 cells. When KU812 cells were cultured with 1 ng/ml IL-4,
      cellular histamine content increased more than 10-fold. IL-4 also enhanced the
      expression of Fc epsilon RI alpha, a high affinity IgE receptor, on the cell
      surface. KU812 cells treated with IL-4 expressed higher levels of Fc epsilon RI
      alpha, Fc epsilon RI beta and Fc epsilon RI gamma mRNA than non treated KU812
      cells. After 21 days in culture with IL-4, KU812 cells became morphologically
      mature basophilic cells as demonstrated by staining positive for cytoplasmic
      granules and heparin proteoglycan by Wright dye and toluidin blue dye
      respectively. In addition, IgE-mediated histamine release was observed,
      suggesting that the Fc epsilon RI induced by IL-4 was functional and was able to
      transduce a signal for degranulation. These results suggest that IL-4 promotes
      differentiation of KU812 cells into mature basophilic cells both morphologically
      and functionally.

PMID- 9647731
TI  - Replication of lambda plasmid DNA in the Escherichia coli cell cycle.
AB  - The Cro repressor autoregulatory loop has long been considered the main
      regulatory process in controlling lambda plasmid replication initiation in
      Escherichia coli. However, we found recently that lambda plasmids can be
      maintained at a constant copy number in the absence of Cro function. Here we
      demonstrate that shortly after inactivation of the Cro repressor, the synthesis
      of lambda plasmid DNA increases significantly but is then stabilized at a level
      similar to that observed in the presence of the Cro function. We found that
      replication initiation of lambda plasmids carrying a functional cro gene proceeds
      randomly in the host cell cycle, but in the absence of Cro function the
      replication initiation of lambda plasmid DNA appears to be cell cycle dependent.
      The host DnaA protein appears to be at least one of the factors involved in the
      cell-cycle-specific control of lambda cro- plasmid replication. Therefore, it
      seems that the lambda cro- plasmid may serve as an amazingly simple model for
      studies on the regulation of DNA replication in the cell cycle.

PMID- 9647732
TI  - STAT3 forms stable homodimers in the presence of divalent cations prior to
      activation.
AB  - We present evidence that the transcription factor STAT3, derived from uninduced
      cells, can form stable homodimers, which are independent of the tyrosine
      phosphorylation status of the protein. The strong interaction, which is resistant
      to many denaturing agents, is dependent on the presence of divalent cations. The
      presence of the homodimer was initially observed in immunoprecipitates of STAT3
      and was detected upon fractionation of cell lysates. These dimers are different
      in structure from dimers observed after cytokine stimulation of cells, which
      results in tyrosine phosphorylation of STAT3 and dimerization involving the SH2
      domain of STAT3.

PMID- 9647733
TI  - Thyroid status and the regulation of thyrotropin-releasing hormone synthesis in
      rat pancreatic islets: comparison with insulin regulation.
AB  - Thyrotropin-releasing hormone (TRH), originally characterized as the first
      hypothalamic hormone, is also synthesized in the insulin-containing cells. TRH
      stimulates the glucagon secretion and attenuates exocrine pancreatic secretions.
      We have previously reported, using whole pancreatic homogenates, that TRH content
      increased in hypothyroid rats, associated to a loss of TRH-degrading activity.
      The present study was undertaken on purified islets, an appropriate model to
      examine thyroid status-dependent regulation of two islet hormones, TRH and
      insulin. The islets from hypothyroid rat pancreas had increased TRH content (4x)
      without any change in insulin content. Likewise, the Northern blot analysis
      revealed that the steady-state concentrations of TRH mRNA increased (4x) while
      those of insulin remain unchanged. These data therefore suggest that TRH gene
      transcription is under the negative control of T3. This study also provides
      insight into islet response to impaired thyroid function.

PMID- 9647734
TI  - Kell and Kx, two disulfide-linked proteins of the human erythrocyte membrane are
      phosphorylated in vivo.
AB  - Kell and Kx are two quantitatively minor proteins from the human erythrocyte
      membrane which carry blood groups antigens and are thought to be a
      metalloprotease and a membrane transporter, respectively. In the red cell
      membrane, these proteins form a complex stabilized by disulfide bond(s).
      Phosphorylation status of these proteins was studied, in the presence or absence
      of effectors of several kinases, either on intact cells incubated with [32P]
      orthophosphate or on ghosts incubated with [gamma-32P]ATP. Purification of Kell
      Kx complex, by immunochromatography on an immobilized human monoclonal antibody
      of Kell blood group specificity allowed to establish that (i) neither protein is
      phosphorylated on tyrosine; (ii) the Kell protein is a putative substrate for
      Casein Kinase II (CKII) and Casein Kinase I (CKI) but not for protein kinase C
      (PKC), whereas Kx protein is phosphorylated by CKII and PKC but not by CKI; (iii)
      Protein Kinase A neither phosphorylates the Kell nor the Kx proteins.

PMID- 9647735
TI  - The first caldesmon-like protein in higher plants.
AB  - Using anti-caldesmon polyclonal and monoclonal (raised against the N-terminal
      fragment of chicken gizzard caldesmon) antibodies, a plant caldesmon-like
      protein, 107 kDa as determined by SDS-gel electrophoresis, has been identified
      based on Western blotting of total extracts of Ornithogalum virens pollen tubes.
      Biochemical investigations showed common properties of this protein with animal
      caldesmon--it binds to actin and, in a Ca(2+)-dependent manner, to calmodulin. In
      contrast to animal caldesmon, this plant cell counterpart is relatively resistant
      to proteolysis by endogenous proteases and sensitive to heat treatment. Our
      results show the presence of a caldesmon-like protein in higher plants for the
      first time.

PMID- 9647736
TI  - Structural characterization and mapping of the normal epithelial cell-specific 1
      gene.
AB  - The normal epithelial cell-specific 1 (NES1) gene is a recently identified novel
      serine protease-like gene which is down-regulated during breast cancer
      progression. The gene product has 34-42% identity with the members of three
      distinct serine protease families: the trypsin-like family, activators of kringle
      domain-containing growth factors, and the kallikrein family (X. L. Liu et al.,
      (1996) Cancer Res 56, 3371-3379). Although the cDNA of this gene has been cloned,
      its genomic structure and chromosomal position are not as yet known. Here, we
      report the genomic characterization and mapping of the NES1 gene. By subcloning
      and sequencing a PAC clone containing the complete NES1 gene, we were able to
      characterize the structure of this gene. The NES1 gene spans 5.5 kb and is
      composed of five coding exons and one untranslated exon. The positions of the
      introns were similar to trypsinogen, prostate specific antigen (PSA), and tissue
      plasminogen activator (TPA). NES1 gene was also localized with somatic cell
      mapping, radiation hybrid mapping, and fluorescence in situ hybridization
      techniques to chromosome 19q13.3-q13.4, the same region where the human
      kallikrein gene family resides. Taken together, our results suggest that the NES1
      gene originates from the same ancestor as trypsinogen, PSA, and TPA, but remains
      in close proximity to PSA.

PMID- 9647737
TI  - Purification from human plasma of a hexapeptide that potentiates the sulfation
      and mitogenic activities of insulin-like growth factors.
AB  - The human plasma contains small peptide molecules known as low molecular weight
      growth factors synergistically increasing certain biological actions of insulin
      like growth factors. In the present work we isolated and characterized a
      hexapeptide with HWESAS as structure. This purified peptide was absolutely
      necessary for the sulfation activity of insulin-like growth factor-I on chick
      embryo pelvic cartilages and improved the mitogenic activity of both insulin-like
      growth factors. The effects of this hexapeptide were confirmed by using the
      homologous synthetic peptide, that exhibited similar biological effects. Other
      synthetic peptides with structure derived from hexapeptide were shown to be
      active: the pentapeptide HWESA appeared more potent than the tripeptide HWE,
      which is about 170 to 200 times less active than the hexapeptide. The sequence of
      hexapeptide HWESAS is identified in only one human protein that is C3f, a
      fragment of C3 complement.

PMID- 9647738
TI  - Formation of fluorescent heme degradation products during the oxidation of
      hemoglobin by hydrogen peroxide.
AB  - Hemoglobin and methemoglobin oxidized by hydrogen peroxide generate
      ferrylhemoglobin and oxoferrylhemoglobin, respectively. Two fluorescent compounds
      were found to be produced during the reaction of oxyhemoglobin, but not
      methemoglobin, with H2O2. These two compounds had excitation wavelengths of 321
      nm and 460 nm, respectively, with emission wavelengths of 465 nm and 525 nm,
      respectively. The formation of the same fluorescent products during the reaction
      of H2O2 with ferroprotoporphyrin-IX and ferriprotoporphyrin-IX demonstrate that
      these compounds originate from the heme moiety. The release of heme iron during
      the formation of these fluorescent compounds indicates that they are associated
      with heme degradation. The time course for the formation of fluorescent products
      show that the extent of heme degradation is dependent on H2O2 concentration. The
      results of this investigation indicate that the heme moiety of Fe(II) hemoglobin
      undergoes degradation in presence of H2O2. The ability to detect this process by
      fluorescence provides a sensitive marker in order to asses hemoglobin and RBC
      oxidative stress under pathological conditions.

PMID- 9647739
TI  - Cloning and characterization of BAI-associated protein 1: a PDZ domain-containing
      protein that interacts with BAI1.
AB  - Brain-specific angiogenesis inhibitor 1 (BAI1), which is a p53-target gene
      specifically expressed in brain, encodes a seven-span transmembrane protein.
      Using a two-hybrid system, we isolated a cDNA that encodes a protein, named BAP1
      (BAI1-associated protein), which interacts with the cytoplasmic region of BAI1.
      BAP1 is a novel member of the MAGUK (membrane-associated guanylate kinase
      homologue) family; it possesses a guanylate kinase domain, WW domains, and
      multiple PDZ domains. Interaction between BAI1 and BAP1 was mediated by a QTEV
      motif in the carboxy-terminal region of BAI1 and PDZ domains of BAP1. By
      immunocytochemical analysis of COS-7 cells transfected with BAI1 and BAP1, both
      products were co-localized at the cytoplasmic membrane, especially at cell-cell
      junctions. Cells transfected with BAI1 formed filopodia-like cytoplasmic
      extensions. These results suggest that BAI1 and BAP1 might be involved in cell
      adhesion and signal transduction in brain.

PMID- 9647740
TI  - Stimulatory effect of endogenous tissue inhibitor of metalloproteinases-1 (TIMP
      1) overexpression on type IV collagen and laminin gene expression in rat mammary
      carcinoma cells.
AB  - We recently reported enhanced tumor growth and stimulation of vascular
      endothelial growth factor (VEGF) expression in rat mammary carcinoma cells
      transfected with a human tissue inhibitor of metalloproteinases-1 (hTIMP-1) cDNA
      (1). In the present study, we examined if the composition of the stroma was
      altered in the tumors with the highest hTIMP-1 production. Immunohistological
      examination revealed increased amounts of the basement membrane (BM) components,
      type IV collagen and laminin, in the hTIMP-1 overexpressing tumors compared to
      that of the control. In vitro studies also revealed upregulation of type IV
      collagen and laminin gene expression associated with the hTIMP-1 overexpression.
      Endogenous RNA levels of rat TIMP-1 and the rat matrix metalloproteinases (MMPs),
      MMP-2, MMP-3, and MMP-9, were not affected by the hTIMP-1 transfection,
      suggesting that the increase in BM deposition was not a result of decreased
      collagenolytic activity. This is the first report to show an association between
      overexpression of TIMP-1 and increased tumor BM matrix production through
      stimulation of type IV collagen and laminin gene expression.

PMID- 9647741
TI  - Severe osteoporosis in mice lacking osteoclastogenesis inhibitory
      factor/osteoprotegerin.
AB  - Osteoclasts are multinucleated cells that resorb bone. Osteoclastogenesis
      inhibitory factor (OCIF), also called osteoprotegerin (OPG), acts as a naturally
      occurring decoy receptor for osteoclast differentiation factor, which mediates an
      essential signal to osteoclast progenitors for their differentiation into
      osteoclasts. Here we show that the OCIF/OPG knockout mice exhibited severe
      osteoporosis due to enhanced osteoclastogenesis when they grew to be adults.
      These mice were viable and fertile. They exhibited marked bone loss accompanied
      by destruction of growth plate and lack of trabecular bone in their femurs. The
      strength of their bones dramatically decreased. These results demonstrate that
      OCIF/OPG is a key factor acting as a negative regulator against
      osteoclastogenesis. The OCIF/OPG knockout mice provide the first animal model for
      osteoporosis without other obvious abnormalities.

PMID- 9647742
TI  - 2-Methoxyestradiol-induced phosphorylation of Bcl-2: uncoupling from JNK/SAPK
      activation.
AB  - The natural estrogen metabolite 2-methoxyestradiol (2ME) is anti-angiogenic in
      vivo and a strong growth inhibitor in vitro. The growth inhibition is due to
      mitotic arrest and apoptosis. These effects are reminiscent of those induced by
      taxol, and appear to be mediated by inhibition of microtubule dynamics. Here we
      have studied the cellular response to 2ME in regard to potential mediators of the
      observed cellular changes. 2ME treatment increases the insoluble polymerized
      fraction of cellular tubulin similar to taxol, and in contrast to the microtubule
      depolymerizing drugs such as colcemid and vincristine. This stabilization
      following 2ME treatment is accompanied by phosphorylation and inactivation of Bcl
      2 increasing gradually from 2-24 hours. To study the pathway leading to Bcl-2
      phosphorylation we analyzed Raf-1 and JNK/SAPK kinases, both of which have been
      reported to be involved in Bcl-2 inactivation. Our results indicate that Raf-1 is
      phosphorylated in response to 2ME, but this occurs later than Bcl-2
      phosphorylation suggesting that Raf-1 is not directly phosphorylating Bcl-2.
      JNK/SAPK was activated rapidly after 2ME treatment. However, this activation was
      transient and returned to undetectable levels by 2 hours of treatment,
      demonstrating that JNK/SAPK is not directly phosphorylating Bcl-2. Taken together
      with previous results indicating that overexpression of JNK/SAPK leads to Bcl-2
      phosphorylation, our results would support a model where JNK/SAPK is indirectly
      phosphorylating Bcl-2.

PMID- 9647743
TI  - Requirement of corepressor binding of thyroid hormone receptor mutants for
      dominant negative inhibition.
AB  - Resistance to thyroid hormone (RTH) is mainly caused by dominant negative
      inhibition of wild type thyroid hormone receptor (TR) function due to mutations
      in the ligand binding domain of the TR beta. Because no RTH mutant was identified
      in the hinge region of the TR, the contribution of this region for dominant
      negative inhibition was explored. In transient transfection assays, the dominant
      negative activity of a RTH-type mutant (P453X) was abolished by an introduction
      of a mutation into the hinge region (P214R). Although this hinge mutation did not
      alter homo- or heterodimerization with retinoid X receptor (RXR), its association
      with nuclear receptor corepressor (N-CoR) was impaired. These results indicate
      that association of corepressor with the RTH mutants through the hinge region is
      crucial for their dominant negative activity.

PMID- 9647744
TI  - Superoxide production in human neutrophils: evidence for signal redundancy and
      the involvement of more than one PKC isoenzyme class.
AB  - Selective protein kinase C (PKC) activators and inhibitors and a physiological
      agonist, fMLP, were used to study superoxide production and PKC isoenzyme
      activation in human neutrophils. The data show that the classical PKC isoenzymes,
      alpha and beta, were activated by TPA and at a time prior to NADPH oxidase
      complex assembly. fMLP induced activation of PKC-beta over a similar time course.
      Inhibition of c-PKCs reduced, but did not block, TPA-induced superoxide
      production completely, suggesting additional PKC isoenzymes were involved beyond
      NADPH oxidase assembly. PKC inhibitors were unable to inhibit fMLP-induced
      superoxide generation, indicative of signal redundancy in the induction of
      superoxide generation in human neutrophils.

PMID- 9647745
TI  - Evidence for role of phospholipase A2 in phosphatidic acid-induced signaling to c
      fos serum response element activation.
AB  - The activity of exogenous phosphatidic acid (PA) to transactivate c-fos serum
      response element (SRE) was investigated by transient transfection analysis.
      Incubation of Rat-2 fibroblast cells with exogenous PA caused a stimulation of c
      fos SRE-linked luciferase activity in a dose- and time-dependent manner. The SRE
      stimulation by PA was dramatically reduced by either pre-treatment with
      mepacrine, an inhibitor of phospholipase A2 (PLA2), or co-transfection with
      antisense cytosolic phospholipase A2 (cPLA2) oligonucleotide, whereas
      lysophosphatidic acid (LPA)-induced SRE activation was not affected. Consistent
      with this specific requirement for PLA2 by PA, the translocation of cPLA2 protein
      was rapidly induced followed by PA treatment. Together, these results suggest
      that PLA2, especially cPLA2, plays a critical role in the nuclear signaling
      cascade of PA in Rat-2 fibroblast cells.

PMID- 9647746
TI  - Molecular characterization of a 28 kDa surface antigen gene family of the tribe
      Ehrlichiae.
AB  - Antisera against different Ehrlichiae recognize an immunodominant, cross-reacting
      approximately 28 kDa surface antigen defined as the MAP1 in Cowdria ruminantium.
      These antigens are considered valuable in developing serodiagnostic tests and
      recombinant vaccines for Ehrlichiae infections. To evaluate the relationship in
      three closely related Ehrlichiae, Ehrlichia chaffeensis, Ehrlichia canis, and C.
      ruminantium, the structure of the 28 kDa antigen genes was analyzed. We describe
      the cloning and characterization of DNA encoding genes homologous to MAP1 from E.
      chaffeensis and E. canis. The cloned segment of E. chaffeensis contains one
      expressed and four transcriptionally silent tandemly arranged, nonidentical
      genes; the E. canis locus consists of two nonidentical genes. Comparative
      analysis of these genes revealed the presence of four conserved regions separated
      by three highly variable regions. B-cell epitope analysis identified three major
      cross-reacting epitopes that map to the variable regions. Location of the
      epitopes at the variable regions and the presence of multigene family with only
      one expressed copy suggest a mechanism of immune evasion in these Ehrlichiae.

PMID- 9647747
TI  - Comparative expression of novel vascular endothelial growth factor/vascular
      permeability factor transcripts in skin, papillomas, and carcinomas of v-Ha-ras
      Tg.AC transgenic mice and FVB/N mice.
AB  - One of the most frequently detected changes in human solid tumors is the mutation
      of the ras oncogene, which has been associated with production of angiogenic
      growth factors such as vascular endothelial growth factor/vascular permeability
      factor (VEGF/VPF). Using the v-Ha-ras Tg-AC transgenic mice and the background
      FVB/N strain of inbred mice, the pattern of expression of specific VEGF/VPF
      transcripts was characterized in major organs and in skin, papillomas, and
      carcinomas during multi-stage skin carcinogenesis. Three VEGF/VPF transcripts
      were found to be constitutively expressed in skin as well as the major organs in
      both mouse strains, which corresponded in size and sequence to previously
      reported murine VEGF120 with a bp size of 331, VEGF164 with a bp size of 333, and
      VEGF188 with a bp size of 407. A previously unreported fourth murine transcript
      was also detected in skin and major tissues from both mouse strains which
      corresponded to rat VEGF144, with a bp size of 404. In addition, a unique 425 bp
      VEGF transcript which corresponded to human VEGF205 was present in highly
      vascularized tissues including heart, lung, liver, kidney, brain, as well in
      papillomas and carcinomas isolated from v-Ha-ras Tg.AC mice. In contrast, VEGF205
      was present only in carcinomas derived from FVB/N mice. An antibody generated
      from a peptide sequence designed to detect each of the five VEGF/VPF peptides
      defined by RT-PCR analysis confirmed the existence of these five peptides and
      confirmed that the murine VEGF205 peptide was selectively expressed in papillomas
      and carcinomas derived from v-Ha-ras Tg.AC mice. These results demonstrate that
      there is significant alternative splicing of the murine VEGF/VPF gene during
      multi-stage carcinogenesis, which results in four commonly expressed VEGF
      transcripts. In addition, these studies identified a fifth VEGF transcript and
      peptide at the later stages of tumor promotion and in progression which appears
      to be linked to the presence of v-Ha-ras.

PMID- 9647748
TI  - Interaction of free fatty acids with human leptin.
AB  - Relatively high concentrations of leptin are present in plasma and it is thought
      to play a major role in lipid homeostasis. Leptin is reported to lower tissue
      triglyceride content by increasing intracellular oxidation of free fatty acids
      (FFA). However very little is known regarding the interaction between leptin and
      plasma FFA. We studied the interaction of FFA with leptin using a direct
      radiolabelled fatty acid binding assay, a fluorescence assay, electrophoretic
      mobility and autoradiobinding. All these data indicate that binding of FFA with
      leptin is reversible and shows a positive co-operativity. The binding of FFA to
      leptin produces a change in the pI value of the leptin and also increased the
      electrophoretic mobility of the protein in native polyacrylamide gels. The change
      in leptin's electrophoretic mobility depends on the chain length and the number
      of double bonds of the fatty acid, as stearic acid, 18:0, had no effect whereas
      oleic acid, 18:1n-9, linoleic acid, 18:2n-6, arachidonic acid, 20:4n-6, and
      docosahexaneoic acid, 22:6n-3, affected leptin's mobility to different degrees.
      The physiological implication of leptin-FFA interaction is not known, however the
      interaction may depend on the plasma FFA composition and concentration which are
      known to vary in different pathological/physiological conditions.

PMID- 9647749
TI  - Peroxide reductase activity of NADH dehydrogenase of an alkaliphilic Bacillus in
      the presence of a 22-kDa protein component from Amphibacillus xylanus.
AB  - The NADH oxidase of Amphibacillus xylanus shows high NADH-peroxide reductase
      activity for hydrogen peroxide and alkyl hydroperoxides in the presence of a 22
      kDa disulfide-containing protein component (Y. Niimura, L. B. Poole, and V.
      Massey, J. Biol.Chem. 270, 25645-25650, 1995). It was found that the membrane
      bound NADH dehydrogenase of an alkaliphilic Bacillus (YN-1) involved in the
      respiratory chain also exhibits reductase activity for hydrogen peroxide and
      cumene hydroperoxide in the presence of the 22-kDa component from Amphibacillus
      xylanus. Vmax values for these substrates were as high as those of the NADH
      oxidase of A. xylanus. Although the 38-kDa protein produced by trypsin treatment
      of NADH dehydrogenase retains NADH dehydrogenase activity, it exhibited no
      peroxide reductase activity in the presence of the 22-kDa component from A.
      xylanus. The NADH dehydrogenase of YN-1 might not only catalyze electron flow
      from NADH to the respiratory chain, but also function for scavenging peroxide.

PMID- 9647750
TI  - Differential deficiency of mevalonate kinase and phosphomevalonate kinase in
      patients with distinct defects in peroxisome biogenesis: evidence for a major
      role of peroxisomes in cholesterol biosynthesis.
AB  - Peroxisomes catalyze a number of essential metabolic functions especially related
      to lipid metabolism. There is increasing evidence suggesting that peroxisomes are
      also involved in the synthesis of isoprenoids via the mevalonate pathway at least
      in rat liver. In order to obtain independent evidence for a role of peroxisomes
      in isoprenoid synthesis in man, we have measured the activity of two key enzymes
      of the mevalonate pathway in patients suffering from certain defined defects in
      peroxisome biogenesis. We now report that mevalonate kinase is not only deficient
      in livers from Zellweger patients in which peroxisome biogenesis is defective,
      but also in livers from rhizomelic chondrodysplasia punctata (RCDP) Type 1
      patients. In the latter group of patients there is a selective defect in
      peroxisome biogenesis due to a genetic defect in the PTS2-receptor, a mobile
      receptor-protein guiding peroxisomal proteins with a certain peroxisomal
      targeting signal (PTS2) to the peroxisome. Phosphomevalonate kinase was found to
      be strongly deficient in Zellweger patients thus suggesting that this enzyme is
      also peroxisomal. Taken together, our data indicate that in human liver
      mevalonate kinase and phosphomevalonate kinase are truly peroxisomal enzymes
      which strongly suggests that peroxisomes play a major role in cholesterol
      biosynthesis.

PMID- 9647751
TI  - pICln predominantly localizes at luminal surface membranes of distal tubules and
      Henle's ascending limbs.
AB  - We produced a highly specific antibody to the C-terminal peptide sequence of
      pICln. It recognized pICln with a 38-kDa molecular mass on SDS-polyacrylamide gel
      electrophoresis, coinciding with that previously reported. During native
      polyacrylamide gel electrophoresis, three immunoreactive bands (38, 70, and 130
      kDa) were detected. The isoelectric point of pICln was calculated to be 4.0.
      Subcellular localization study showed the presence of pICln in the soluble and
      microsomal fraction. pICln can be easily solubilized from the membrane fraction
      with Triton X-100. From immunohistochemical observations, we found pICln to be
      obviously located on the luminal surface membranes of the distal tubules and
      Henle's loop ascending limbs, and it can also be found inside proximal tubular
      cells. The present results suggested that pICln functions as a "cytosolic anchor
      = membrane insertion" model, and it plays important roles in the "urine dilution
      segment" cells of nephrons.

PMID- 9647752
TI  - Determinants of recombinant production of antimicrobial cationic peptides and
      creation of peptide variants in bacteria.
AB  - Cationic peptides possessing antibacterial activity are virtually ubiquitous in
      nature, and offer exciting prospects as new therapeutic agents. We had previously
      demonstrated that such peptides could be produced by fusion protein technology in
      bacteria and several carrier proteins had been tested as fusion partners
      including glutathione-S-transferase, S. aureus protein A, IgG binding protein and
      P. aeruginosa outer membrane protein OprF. However these fusion partners, while
      successfully employed in peptide expression, were not optimized for high level
      production of cationic peptides (Piers, K., Brow, M. L., and Hancock, R. E. W.
      1993, Gene 137, 7-13). In this paper we took advantage of a small replication
      protein RepA from E. coli and used its truncated version to construct fusion
      partners. The minimal elements required for high level expression of cationic
      peptide were defined as a DNA sequence encoding a fusion protein comprising, from
      the N-terminus, a 68 amino acid carrier region, an anionic prepro domain, a
      single methionine and the peptide of interest. The 68 amino acid carrier region
      was a block of three polypeptides consisting of a truncated RepA, a synthetic
      cellulose binding domain and a hexa histidine domain. The improved system showed
      high level expression and simplified downstream purification. The active peptide
      could be yielded by CNBr cleavage of the fusion protein. This novel vector was
      used to express three classes of cationic peptides including the alpha-helical
      peptide CEMA, the looped peptide bactenecin and the extended peptide indolicidin.
      In addition, mutagenesis of the peptide gene to produce peptide variants of CEMA
      and indolicidin using the improved vector system was shown to be successful.

PMID- 9647753
TI  - Molecular cloning, expression, and functional characterization of novel mouse
      sulfotransferases.
AB  - Nucleotide sequences of two mouse cDNAs encoding new sulfotransferase enzymes
      were determined. Analysis of the deduced amino acid sequences revealed that one
      represents a novel member of the phenol sulfotransferase family and the other is
      highly homologous to human SULT2B1 hydroxysteroid sulfotransferases. The
      recombinant enzymes, transiently expressed in COS-7 cells, were characterized
      with respect to their substrate specificity using a variety of substrates for
      different types of sulfotransferases. The tissue-specific expression of these two
      new mouse sulfotransferases was examined by Northern blot analysis.

PMID- 9647754
TI  - The bilirubin-binding motif of bilitranslocase and its relation to conserved
      motifs in ancient biliproteins.
AB  - In the primary structure of bilitranslocase, currently under study in our
      laboratory, an aminoacid motif was identified and found to be conserved in a
      number of alpha-phycocyanines, ancient biliproteins present in cyanobacteria. To
      test the possibility that such a motif could be at least part of the binding site
      for bilirubin, epitope-specific antibodies were raised. The target corresponds to
      the sequence 65-75 of bilitranslocase and covers the central portion of the motif
      identified. The antibodies were shown: 1) to inhibit the electrogenic BSP
      transport by plasmamembrane vesicles; 2) to react with purified bilitranslocase;
      and 3) to identify only one protein band with electrophoretic mobility identical
      to bilitranslocase in Western blots of solubilised plasmamembrane vesicles. The
      presence of either bilirubin or nicotinate during pre-incubation with the
      antibodies decreases concentration-wise the inhibition kinetics. From these
      experiments a dissociation constant of 2.2 +/- 0.3 and 11.3 +/- 1.3 nM for
      bilirubin-bilitranslocase and nicotinate-bilitranslocase complexes were
      calculated.

PMID- 9647755
TI  - Role of ultraviolet A-induced oxidative DNA damage in apoptosis via loss of
      mitochondrial membrane potential and caspase-3 activation.
AB  - UVA has been implicated in multistage photocarcinogenesis. HPLC analysis revealed
      that the 7,8-dihydro-8-oxo-2'-deoxyguanosine content of DNA in HL-60 cells
      increased immediately after UVA irradiation. Pulsed field gel electrophoresis
      showed that cellular DNA strand breakage was induced at 1 h after UVA
      irradiation. Flow cytometry showed that mitochondrial membrane potential (delta
      psi m) decreased time-dependently in cells exposed to UVA. The activity of
      caspase-3 and DNA ladder formation increased at 2 h after UVA irradiation. These
      results suggest that UVA irradiation induces oxidative DNA damage, followed by
      the loss of delta psi m and subsequent activation of caspase-3, resulting in
      apoptosis.

PMID- 9647756
TI  - Hammerhead ribozymes against gamma-glutamylcysteine synthetase mRNA down-regulate
      intracellular glutathione concentration of mouse islet cells.
AB  - gamma-Glutamylcysteine synthetase (gamma-GCS) is a key enzyme in glutathione
      synthesis and is thought to play a significant role in intracellular
      detoxification systems. To specifically suppress gamma-GCS gene expression, we
      constructed two different hammerhead ribozymes against gamma-GCS mRNA
      transcripts. Two cleavage sites were targeted as follows: site 1 for anti-gamma
      GCS ribozyme (H), a GUU triplet located from +348 to +350 of the gamma-GCS heavy
      chain, and site 2 for anti-gamma-GCS ribozyme (L), a GUU triplet located from
      +235 to +237 of the gamma-GCS light chain. The anti-gamma-GCS ribozymes
      effectively cleaved gamma-GCS mRNA in a cell-free system. When transfected into a
      Min-6 mouse islet cell line, these anti-gamma-GCS ribozymes not only suppressed
      gamma-GCS gene expression, but also reduced intracellular glutathione
      concentration. These results suggest that the ribozyme-mediated down-regulation
      of gamma-GCS gene expression may be useful for analyzing the glutathione
      associated cellular defense systems of pancreatic islet cells.

PMID- 9647757
TI  - Characterization of two UDP glucuronosyltransferases that are predominantly
      expressed in human colon.
AB  - The liver and gastrointestinal tract are major sites of drug metabolism. However,
      although the UDP glucuronosyltransferase family of drug-metabolizing enzymes has
      been extensively characterized in the liver, little is known about this family in
      the gastrointestinal tract. In this work, an analysis of human colon RNA samples
      revealed the presence of two UDP glucuronosyltransferase forms that could not be
      detected in human liver. The cDNA encoding these two forms, UGT1A8 and UGT1A10,
      was synthesized and expressed in COS-7 cells. Both proteins have molecular masses
      of 56 kDa and are active towards hydroxylated metabolites of the carcinogens,
      benzo(alpha)pyrene and 2-acetylaminofluorene. UGT1A8 was most active towards the
      10- and 11-hydroxy benzo(alpha)pyrenes and the preferred 2-acetylaminofluorene
      metabolites were the 1-, 2-, and 8-hydroxy derivatives. UGT1A10 was most active
      towards the 11- and 12-hydroxybenzo(alpha)pyrenes and the 1- and 3-hydroxy
      derivatives of 2-acetylaminofluorene. Both enzymes were inactive towards the
      benzo(alpha)pyrene trans 4, 5 and 7, 8 dihydrodiols. In addition, these UDP
      glucuronosyltransferases displayed differential activity towards several phenolic
      substrates. A survey of human tissues indicated that UGT1A8 and UGT1A10
      transcripts are predominantly expressed in the gastrointestinal tract, in
      contrast to most other UDP glucuronosyltransferase forms which are expressed in
      the liver and other tissues. These results suggest that UGT1A8 and UGT1A10 may
      play an important role in the metabolism of dietary xenobiotics.

PMID- 9647758
TI  - Identification of a novel isoform of microphthalmia-associated transcription
      factor that is enriched in retinal pigment epithelium.
AB  - Mutations at the mouse locus encoding microphthalmia-associated transcription
      factor (Mitf) affect the development of many cell types, including retinal
      pigment epithelium (RPE), melanocytes, mast cells, and osteoclasts. Here we have
      identified a novel Mitf isoform, Mitf-a, and its human homologue MITF-A by cDNA
      cloning. MITF-A consists of 520 amino acid residues and differs in the amino
      terminus from authentic melanocyte-type MITF (MITF-M). MITF-A mRNA is widely
      expressed and represents a predominant MITF isoform in cultured RPE cells,
      whereas MITF-M mRNA is exclusively expressed in melanocytes and melanoma cells.
      In situ hybridization analysis suggested that Mitf-a mRNA is enriched in the
      prospective RPE of mouse embryo. Moreover, transient cotransfection assays
      suggested that MITF-A activated transcription of the tyrosinase and tyrosinase
      related protein 1 genes. MITF-A/Mitf-a therefore may play an important role in
      melanogenesis in RPE.

PMID- 9647759
TI  - A regulatory role of sulfhydryl groups in modulation of sperm membrane
      conformation by heavy metals: sulfhydryl groups as markers for infertility
      assessment.
AB  - Sperm membrane sulfhydryl groups, when masked by heavy metals like cobalt and
      copper at very low concentration (10(-9)) shows inhibition of lipid peroxidation
      and superoxide dismutase activity. Inhibition of lipid peroxidation is suggested
      to lead to reduction in membrane fluidity, a prerequisite for normal sperm
      function. Augmentation of lipid peroxidation by pentoxifylline in oligospermia
      provides evidence to this hypothesis that membrane sulfhydryls play a regulatory
      role in membrane modulation. It is therefore suggested that these sulfhydryl
      groups can be used as a tool for infertility assessment in unexplained male
      infertility.

PMID- 9647760
TI  - Reduction of 4-hydroxynonenal and 4-hydroxyhexenal by retinal aldose reductase.
AB  - Aldose reductase has been purified to homogeneity from bovine retina. It has an
      apparent molecular weight of 32,000 daltons and shares immunological and kinetic
      properties with the much studied aldose reductases purified from various sources.
      Retinal aldose reductase displays a K(m) of approximately 40 microM with 4
      hydroxynonenal and 4-hydroxyhexenal, the oxidation end products of arachidonic
      and docosahexanoeic acids, respectively. It therefore appears that aldose
      reductase may constitute a major detoxification route of these toxic aldehydes in
      the retina.

PMID- 9647761
TI  - Structural variations in nisin associated with different membrane mimicking and
      pH environments.
AB  - Nisin is a membrane active antimicrobial peptide containing unusual dehydrated
      amino acid residues. The secondary structure of nisin in aqueous solution,
      membrane mimicking solvents and at various pH values was investigated using
      circular dichroism. In aqueous solution nisin is largely randomly coiled. In
      liposomes and at pH 6 and above, however, the presence of a maximum at 195 nm and
      a minimum at 190 nm was notable and indicative of beta-turn formation in these
      environments. This change in structure was speculated to result in an increasing
      unavailability of the site for initial reaction of peptide and membrane at higher
      pH.

PMID- 9647762
TI  - Identification of cDNAs induced by the tumor suppressor Tsc2 gene using a
      conditional expression system in Tsc2 mutant (Eker) rat renal carcinoma cells.
AB  - Alteration of the rat homologue of the tuberous sclerosis 2 (TSC2) gene is
      associated with dominantly inherited cancer in the Eker rat model, indicating a
      tumor suppressor nature. The ability of Tsc2 to activate signal transduction and
      transcription suggests that genes induced by Tsc2 may mediate its biological
      roles. Using a subtractive hybridization approach in combination with
      tetracycline operator systems, we identified a set of downstream genes affected
      by Tsc2. Regulated expression of wild-type Tsc2 gene in Eker renal carcinomas
      (RCs) resulted in marked expression of cell arrest or programmed cell-death
      related genes and stress-induced genes. Thus, the data suggest that Tsc2 might
      contribute to regulation of the cell cycle and cell survival.

PMID- 9647763
TI  - The covalent structure of the blue copper-containing nitrite reductase from
      Achromobacter xylosoxidans.
AB  - The complete amino acid sequence of the blue copper-containing nitrite reductase
      enzyme (NiR) from Achromobacter xylosoxidans has been determined by chemical
      analysis, supported by high precision mass analysis. The polypeptide chain
      contains 336 residues with an overall charge of 0, including the +2 state of each
      of the copper ions. The two NiR enzymes for which the three-dimensional
      structures have been solved are green in color and have different absorption
      spectra than those of the blue-colored protein from A. xylosoxidans. The ligands
      to the two copper atoms are conserved. Therefore, the difference between the blue
      and the green NiR must depend on subtle changes in the geometry of the type I
      copper-sulfur bond. Both overall protein charge and active site charge are
      different in A. xylosoxidans NiR which may reflect the use of azurin as electron
      donor as opposed to the other enzymes that use pseudoazurin.

PMID- 9647764
TI  - Cloning of the histidine biosynthetic genes of Corynebacterium glutamicum:
      organization and sequencing analysis of the hisA, impA, and hisF gene cluster.
AB  - The hisA and hisF genes of Corynebacterium glutamicum were cloned by transforming
      histidine auxotrophic Escherichia coli with the genomic DNA library. They are two
      of the eight genes that participate in the histidine biosynthetic pathway. Cloned
      DNA fragments containing the genes can also complement hisH and hisI auxotrophs
      of Escherichia coli, suggesting that the four genes are clustered in the genome.
      We determined the nucleotide sequences of the minimal fragment containing the
      hisA and hisF genes, which are separated by the impA gene. The coding regions of
      the hisA and hisF genes are 245 and 257 amino acids in length with a predicted
      size of about 26 and 27 kDa, respectively. These are in good agreement with the
      sizes of proteins expressed in E. coli. A high similarity was observed in
      comparison of nucleotide sequences of each protein between C. glutamicum and
      other species, as well as those between hisA and hisF genes of C. glutamicum.

PMID- 9647765
TI  - Molecular and crystal properties of Bos d 2, an allergenic protein of the
      lipocalin family.
AB  - The relationship between the molecular structure of allergenic proteins and the
      allergenic determinants is one of the central issues in allergology. We report
      here that the natural preparation of Bos d 2, a mammalian lipocalin allergen,
      comprises three molecular variant proteins of 17,829, 17,781, and 17,800 Da. When
      cDNA of Bos d 2 (Genome Sequence Data Base No. L42867) was recloned and expressed
      in Pichia pastoris, two proteins were produced. One of the proteins (17,831 Da)
      and the proteins in the natural preparation had pyroglutamate as the N-terminal
      residue; in the other (17,849 Da) the N-terminal residue was glutamine.
      Recombinant Bos d 2 protein was crystallized and the native data set was
      collected at 1.8 A resolution.

PMID- 9647766
TI  - cDNA sequence and chromosomal localization of the remaining three human nuclear
      encoded iron sulphur protein (IP) subunits of complex I: the human IP fraction is
      completed.
AB  - NADH:ubiquinone oxidoreductase (complex I) of the mitochondrial respiratory chain
      can be fragmented in a flavoprotein (FP), iron-sulfur protein (IP), and
      hydrophobic protein (HP) subfraction. The IP subfraction is hypothesized to be
      significant, since it contains important prosthetic groups highly conserved among
      species. We cloned the cDNA of three remaining human NADH:ubiquinone
      oxidoreductase subunits of this IP fraction: the NDUFS2 (49 kDa), NDUFS3 (30
      kDa), and NDUFS6 (13 kDa) subunits. All presented cDNAs include the complete open
      reading frame (ORF), which consist of 1392, 795, and 375 base pairs, coding for
      463, 264, and 124 amino acids, respectively. The latter show 96, 90, and 83%
      homology with the corresponding bovine translation products. The 3' untranslated
      regions (UTR) are complete in all three cDNAs. Polymerase chain reaction
      performed with DNA isolated from somatic human-rodent cell hybrids containing
      defined human chromosomes as template gave a human-specific signal which mapped
      the NDUFS2 and NDUFS3 subunits to chromosomes 1 and 11, respectively. In the case
      of the NDUFS6 subunit a pseudogene may be present since signals were seen in the
      lanes containing chromosomes 5 and 6. The NDUFS2 contains a highly conserved
      protein kinase C phosphorylation site and the NDUFS3 subunit contains a highly
      conserved casein kinase II phosphorylation site which make them strong candidates
      for future mutation detection studies in enzymatic complex I-deficient patients.

PMID- 9647767
TI  - Trimidox-mediated morphological changes during erythroid differentiation is
      associated with the stimulation of hemoglobin and F-cell production in human K562
      cells.
AB  - Trimidox (3,4,5-trihdroxybenzamidoxime) has been shown to reduce the activity of
      ribonucleotide reductase with accompanied growth inhibition and differentiation
      of mammalian cells. Hydroxyurea (HU) is the only ribonucleotide reductase
      inhibitor in clinical use for the treatment and management of sickle cell anemia,
      since this compound increases fetal hemoglobin (Hb F) production: a potent
      inhibitor of sickle hemoglobin (Hb SS) polymerization. However, the main
      limitations of HU is its lack of potency, myelosuppression and short half life.
      These studies investigated the effects of trimidox on the induction of hemoglobin
      and F-cells production in K562 erythroleukemia cells. Our study reveals that
      trimidox exhibits concentration dependent inhibitory effect on K562 cells with
      increase in benzidine positive normoblasts and F-cells production as well as
      morphological changes typical of erythroid differentiation. These findings
      provide the first evidence that the growth inhibitory differentiation of cells
      induced by trimidox enhance hemoglobin and F-cells production.

PMID- 9647768
TI  - Extra-chromosomal telomere repeat DNA in telomerase-negative immortalized cell
      lines.
AB  - We found novel extra-chromosomal telomere repeat (ECTR) DNAs in telomerase
      negative immortalized KMST-6 cells, by staining these cells with a (TTAGGG)n
      probe using both cycling oligonucleotide-primed in situ synthesis and by
      fluorescence in situ hybridization. Relatively small amounts of ECTR DNAs were
      also observed in telomerase-negative VA13 and SUSM-1 cells, but not observed in
      telomerase-positive immortalized HeLa cells. The ECTR DNAs existed mainly in the
      nucleoplasm with a small amount in the cytoplasm. The nucleoplasm ECTR DNAs were
      co-stained with an antibody directed to the telomeric-repeat binding factor 1
      (TRF1), suggesting that they exist as a complex with TRF1. In consistent with
      these cytological studies, Southern blot analysis showed the existence of small
      telomere repeat DNAs. The ECTR DNA may provide an insight into the elucidation of
      the mechanisms responsible for the maintenance of telomeres in telomerase
      negative immortalized cells.

PMID- 9647769
TI  - Different modes of cell death induced by 5-fluoro-2'-deoxyuridine in two clones
      of the mouse mammary tumor FM3A cell line.
AB  - The mode of cell death induced by 1 microM 5-fluoro-2'-deoxyuridine (FdUrd)
      changed in a wild-type F28-7 clone of mouse mammary tumor FM3A cells after a six
      month culture. In the original stocked F28-7 clone, FdUrd-induced cell death was
      accompanied by necrosis-like cell swelling and DNA fragmentation to 100-200 kbp.
      In subclone F28-7-A isolated from F28-7 cells, which had been cultured for six
      months, apoptotic bodies and nucleosomal DNA-ladder fragments were observed with
      the treatment. Furthermore, we investigated the differences in FdUrd-induced
      intracellular signals between these clones. In F28-7 cells, FdUrd induced
      increases in caspase-3-like activity, and the mRNA levels of the c-jun, c-fos and
      c-myc genes, which were greater and earlier than those in F28-7-A cells.
      Moreover, intracellular acidification occurred in F28-7-A cells treated with
      FdUrd, though it was not observed in F28-7 cells. These findings suggest that
      FdUrd-induced cell death occurred through the death program to cell lysis
      (necrosis) without apoptosis when the induction of these intracellular signals
      was very high and when intracellular acidification was deficient. Investigation
      of the differences in the mode of FdUrd-induced cell death between these clones
      would be important for elucidating the molecular mechanism of pivotal events
      guiding cells toward either apoptosis or necrosis.

PMID- 9647770
TI  - Detection of activated Caspase-3 by a cleavage site-directed antiserum during
      naturally occurring DRG neurons apoptosis.
AB  - We prepared a cleavage site-directed antiserum against Caspase-3 (anti-p20/17),
      which reacts with the p20/17 fragment (p20/17) activated by cleavage but not
      proCaspase-3 (p32), and examined the relationship between the activation of
      Caspase-3 and apoptosis. We identified p20/17-positive cells where cell death
      occurs naturally: interdigits of the forelimbs, small intestine epithelium,
      thymus, trigeminal ganglia, and dorsal root ganglia of mouse embryos. Withdrawal
      of nerve growth factor induced the appearance of p20/17-positive cells with DNA
      fragmentation in the culture of dorsal root ganglia neurons, while DNA
      fragmentation was detected in both p20/17-positive and -negative neurons in
      dorsal root ganglia of mouse embryos. These results suggest that not only
      activation of Caspase-3 but also other molecular mechanism play a role in the
      naturally occurring dorsal root ganglia apoptosis. Cleavage site-directed
      antisera against Caspases will be useful for the analysis of the molecular
      mechanism of naturally occurring apoptosis during development.

PMID- 9647771
TI  - Rapid determination of gap junction formation using HeLa cells microinjected with
      cDNAs encoding wild-type and chimeric connexins.
AB  - A procedure for rapidly determining the functionality of gap junctions
      constructed of recombinant connexins in communication-deficient HeLa cells is
      described. Nuclear microinjection of cDNA encoding wild-type connexins (Cx) 26,
      32, 43, and a range of connexin-aequorin (Cx-Aeq) chimerase resulted in
      generation of gap junction intercellular communication channels. Expression of
      recombinant protein was detected in > 95% of cells 18-72 h following nuclear
      microinjection, and the functionality of the channels generated was determined
      according to their ability to transfer the fluorescent dye tracers Lucifer yellow
      and propidium iodide. The dye transfer results obtained correlated closely with
      other published studies using stably transfected cells and yet are obtained as
      rapidly as 18 h following microinjection of cDNA. Expression of a truncated form
      of Cx43 (Cx43 delta 244) by this new method indicated diminished intercellular
      transfer of both dyes and supports a channel-gating mechanism that postulates
      interaction between the carboxyl tail and the intracellular loop.

PMID- 9647772
TI  - Foam cell conversion of macrophages alters the biosynthesis of heparan sulfate.
AB  - Heparan sulfate is thought to regulate the biological activities of several
      proteins implicated in the pathogenesis of atherosclerosis. While the
      interactions of heparan sulfate with lipoprotein lipase and various growth
      factors have been actively studied, little is known of the cellular regulation of
      heparan sulfate biosynthesis in response to lipid accumulation. We have
      investigated heparan sulfate biosynthesis during conversion of murine J774
      macrophages into lipid-laden foam cells. Such conversion is shown to accelerate
      the rate of glycosaminoglycan synthesis and the transport of newly synthesized
      proteoglycans into the medium. Moreover, the structure of heparan sulfate is
      specifically altered due to an approximately 30% increase in the 6-O-sulfation of
      glucosamine residues within the N-sulfated heparan sulfate domains, whereas the
      sulfation of chondroitin sulfate remains unaffected. These results suggest a
      selective effect of foam cell conversion on the biosynthesis of heparan sulfate.

PMID- 9647773
TI  - Induction of Apg-1, a member of the heat shock protein 110 family, following
      transient forebrain ischemia in the rat brain.
AB  - Apg-1 (Osp94) and apg-2 belong to the heat shock protein (hsp) 110 family. In
      mouse somatic cells the apg-1 and hsp105/110 transcripts are inducible by a 32
      degrees C to 39 degrees C heat shock, while apg-2 is not heat-inducible. Since
      ischemia is known to induce expression of hsp70, its effect on expression of apg
      1 was assessed by using the 20-min forebrain ischemia model of the rat. In the
      cerebral cortex, Northern blot analysis and in situ hybridization histochemistry
      demonstrated an increased expression in neuronal cells of apg-1 transcripts 3 h
      after the onset of reperfusion, with a peak at 12 h, followed by a decline. In
      the hippocampus, the level was increased at 3 h, remained constant until 24 h,
      and then declined. Transcript levels of apg-2 as well as hsp 105 were also
      increased under the present conditions, indicating that the expression of apg-2
      was differentially regulated in response to heat and ischemic stresses. The
      induction kinetics of hsp 105, but neither apg-2 nor hsp 70, were identical to
      those of apg-1. These results demonstrated that brain ischemia/reperfusion
      induced expression of each member of the hsp 110 family, although the regulatory
      mechanisms may not be the same. They also suggest a significant role of apg-1 in
      both the ischemic- and heat-stress responses and in the normal functioning of the
      non-stressed neuronal cells.

PMID- 9647774
TI  - Interferon-gamma-induced differentiation and apoptosis of HT29 cells:
      dissociation of (glucosyl)ceramide signaling.
AB  - Recently, (glyco)sphingolipids (SL) like ceramide (Cer) and glucosylceramide
      (GlcCer) have been shown to be involved in signaling pathways leading to
      differentiation and apoptosis in several cell types, including the colon
      adenocarcinoma cell line HT29. Intracellular levels of Cer can be modulated by
      ligands such as interferon-gamma (IFN gamma). In the present study we show that
      IFN gamma, depending on its concentration, has both differentiation- and
      apoptosis-inducing effects on HT29 cells. Since both phenomena have been related
      to SL-mediated signaling in other cell types, we next examined whether IFN gamma
      was able to induce changes in the SL levels of HT29 cells. Remarkably, no
      significant changes in these levels could be revealed, implying that SL are not
      involved in IFN gamma-induced differentiation and/or apoptosis of HT29 cells.
      This observation provides evidence for the hypothesis that SL-mediated signaling
      pathways might be more cell type specific than is generally assumed.

PMID- 9647775
TI  - Nitric oxide inhibits c-Jun N-terminal kinase 2 (JNK2) via S-nitrosylation.
AB  - S-nitrosylation by S-nitrosoglutathione (GSNO), a nitric oxide (NO) donor,
      suppresses the phosphotransferase activity of cJun N-terminal kinase 2
      (JNK2)/stress activated protein kinase (SAPK) in dose- and time-dependent manners
      in vitro. JNK2 activity is significantly decreased at 10 microM of GSNO, which is
      dramatically reversed by adding 10 mM of DTT. Reduced form of glutathione
      protects the GSNO-induced suppression of JNK2 activation in a dose-dependent
      fashion. However, GSNO-treated Sek1 does not affect the JNK2 activity of
      phosphotransferation toward c-Jun N-terminal1-79 protein. These results indicate
      that NO may exert a regulatory role of JNK2 activity by S-nitrosylation of the
      protein in apoptotic signaling pathway. Suppression of JNK2 phosphotransferase
      activity by NO is also supported by the observation that NO plays an important
      anti-apoptotic roles in heptocytes, splenocytes, eosinophils and B lymphocytes.

PMID- 9647776
TI  - Isolation and characterization of the mouse beta 2/neuroD gene promoter.
AB  - Beta2/neuroD is a basic helix-loop-helix protein involved in differentiation of
      the endocrine pancreas and the central nervous system. A 2-kb fragment containing
      the 5' upstream region of the mouse beta2/neuroD gene was cloned and sequenced.
      The cloned fragment was tested for promoter activity in six cell lines. Strong
      promoter activity was apparent in the three pancreatic beta cell lines, beta-HC3,
      beta-HC9, and NIT-1, whereas weak activity was seen in NIH 3T3, Rat-1, and MCF-7
      cell lines. Analysis of promoter activity of deletion mutants in beta-HC3 cells
      indicated that while basal promoter activity was observed with a fragment which
      extended -109 bp upstream of the transcription start site, maximal activity
      required the fragment -2091 to -297 bp.

PMID- 9647777
TI  - Stimulation of primed neutrophils by soluble immune complexes: priming leads to
      enhanced intracellular Ca2+ elevations, activation of phospholipase D, and
      activation of the NADPH oxidase.
AB  - Soluble immune complexes activate a rapid burst of reactive oxidant secretion
      from neutrophils that have previously been primed with GM-CSF. Binding of these
      complexes to the cell surface of unprimed neutrophils results in the generation
      of intracellular Ca2+ transients, but the NADPH oxidase fails to become
      activated. No phospholipase D activity was observed following the addition of
      soluble immune complexes to unprimed cells. Upon priming with GM-CSF, the
      intracellular Ca2+ signal generated following soluble complex binding was greatly
      extended and phospholipase D was activated: there was also increased
      phosphorylation of proteins on tyrosine residues and the NADPH oxidase was
      activated. When Ca2+ influx was prevented, this phospholipase D activity was not
      observed. This primed oxidase activity was completely inhibited by erbstatin.
      Treatment of unprimed neutrophils with pervanadate (to inhibit protein tyrosine
      phosphatases) mimicked the effects of priming in that pervanadate-treated
      neutrophils secreted reactive oxidants in response to soluble immune complexes.
      The data indicate that during priming a new signaling pathway is activated that
      involves Ca2+ influx, phosphorylation on tyrosine residues, phospholipase D
      activity, and NADPH oxidase activation.

PMID- 9647778
TI  - Alpha 4 associates with protein phosphatases 2A, 4, and 6.
AB  - Protein phosphatases participate in the regulation of a variety of cellular
      processes. Control of their enzymatic activity and specificity is made possible
      largely by an array of regulatory subunits. Novel serine/threonine phosphatases-
      PP4 and PP6 in human cells--have been discovered recently, for which regulatory
      subunits are yet to be identified. We report here the identification of a
      potential regulatory subunit of these phosphatases. Using the yeast two-hybrid
      system, we have found that alpha 4, a previously identified phosphoprotein,
      associates constitutively with the catalytic subunits of PP4, PP6, and both
      isoforms of PP2A. These interactions have been confirmed by direct binding and do
      not require phosphorylation of alpha 4, although it is unclear whether alpha 4
      phosphorylation has any effect on its association with the phosphatases. The
      binding activity appears to reside in the N-terminal 50 amino acids of the
      phosphatases, consistent with a previous observation that the first 55 residues
      of PPV, a Drosophila homolog of PP6, may harbor the element for regulation. alpha
      4 shares 37% sequence homology with Tap42, an S. cerevisiae protein that has been
      reported to associate with PP2A and Sit4 (yeast homolog of PP6) and comprises a
      regulatory component in the rapamycin-sensitive Tor signalling pathway. By
      analogy, alpha 4 and its associated phosphatases may participate in the mammalian
      rapamycin-sensitive pathway mediated by FRAP.

PMID- 9647779
TI  - Differential expression of human histone deacetylase mRNAs in response to immune
      cell apoptosis induction by trichostatin A and butyrate.
AB  - The reversible acetylation of histones by histone deacetylases (HDACs) and
      acetyltransferases (HATs) plays a fundamental role in gene transcription. We
      previously showed that HDAC mRNA is upregulated in immune cells upon PHA-induced
      activation. Little is known, however, about the differential regulation of HDAC
      mRNAs by the HDAC inhibitors Trichostatin A (TSA) and butyrate, agents known to
      block proliferation and induce apoptosis. We report that apoptosis-inducing
      concentrations of TSA and butyrate upregulate the expression of HDAC mRNAs in a
      differential manner and act synergistically with PHA to induce HDAC expression,
      suggesting the presence of independent HDAC regulatory mechanisms. Moreover, we
      show that HDAC inhibitor-induced apoptosis is associated with early abrogation of
      gamma-IFN production by Th1 lymphocytes and with p53 mRNA downregulation. Our
      findings highlight the dynamic interplay of cell cycle-, activation- and
      apoptosis-related proteins in association with time-dependent expression of HDACs
      and are suggestive of different specific roles for these enzymes.

PMID- 9647780
TI  - Potent inhibition of CTLA-4 expression by an anti-CTLA-4 ribozyme.
AB  - Blockading the negative-regulatory CTLA-4 receptor has emerged as a powerful
      strategy with clinical potential to enhance T-cell responses. Some experimental
      tumors, for example, are rejected when anti-CTLA-4 antibodies are administered in
      vivo. The concise target cells and downstream events, however, remain to be
      defined. The development of gene transfer reagents that inhibit CTLA-4 may
      facilitate such investigations and may expand the therapeutic range. This
      communication describes an anti-CTLA-4 hairpin ribozyme that specifically
      abrogates CTLA-4 expression after gene transfer into a murine T-cell model. The
      analysis of multiple and independently derived clones and bulk cultures showed
      that CTLA-4 induction was inhibited > 90% at the RNA level and that it was
      undetectable at the protein level, with and without selective pressure. This
      potent inhibition required the catalytic function of the ribozyme. The anti-CTLA
      4 ribozyme may be an alternative tool with which to continue the functional and
      therapeutical exploration of CTLA-4.

PMID- 9647781
TI  - Run-down of L-type Ca2+ channels occurs on the alpha 1 subunit.
AB  - Run-down of L-type Ca2+ channels in CHO cells stably expressing alpha 1c, alpha
      1c beta 1a, or alpha 1c beta 1a alpha 2 delta gamma subunits was studied using
      the patch-clamp technique (single channel recording). The channel activity (NPo)
      of alpha 1c channels was increased 4- and 8-fold by coexpression with beta 1a and
      beta 1a alpha 2 delta gamma, respectively. When membranes containing channels
      composed of different subunits were excised into basic internal solution, the
      channel activity exhibited run-down, the time-course of which was independent of
      the subunit composition. The run-down was restored by the application of
      calpastatin (or calpastatin contained in cytoplasmic P-fraction) + H-fraction (a
      high molecular mass fraction of bovine cardiac cytoplasm) + 3 mM ATP, which has
      been shown to reverse the run-down in native Ca2+ channels in the guinea-pig
      heart. The restoration level was 64.7, 63.5, and 66.4% for channels composed of
      alpha 1c, alpha 1c beta 1a, and alpha 1c beta 1a alpha 2 delta gamma,
      respectively, and was thus also independent of the subunit composition. We
      conclude that run-down of L-type Ca2+ channels occurs via the alpha 1 subunit and
      that the cytoplasmic factors maintaining Ca2+ channel activity act on the alpha 1
      subunit.

PMID- 9647782
TI  - WNT-1 and HGF regulate GSK3 beta activity and beta-catenin signaling in mammary
      epithelial cells.
AB  - Wnt-1, a secreted glycoprotein, participates in development of the nervous system
      and contributes to mammary oncogenesis when overexpressed. We show that GSK3
      activity is decreased in mouse mammary cells transformed by Wnt-1. These cells
      also exhibit a substantial Wnt-1 dependent increase in the uncomplexed population
      of beta-catenin. Wnt-1 signaling does not change the steady state level of either
      GSK3 alpha or GSK3 beta but instead leads to an increased association between
      GSK3 beta and beta-catenin. HGF/SF treatment of mouse mammary cells also leads to
      a transient decrease in GSK3 activity and a parallel, selective increase in the
      uncomplexed pool of beta-catenin. Both Wnt-1 and HGF/SF lead to nuclear
      accumulation of beta-catenin and activation of a LEF/Tcf responsive reporter
      gene. This study defines a pivotal signal transduction pathway, activated by both
      Wnt-1 and HGF/SF, leading to decreased GSK3 beta activity and consequently an
      increase in the free pool and nuclear accumulation of beta-catenin and changes in
      gene expression.

PMID- 9647783
TI  - Doxorubicin- and daunorubicin-glutathione conjugates, but not unconjugated drugs,
      competitively inhibit leukotriene C4 transport mediated by MRP/GS-X pump.
AB  - Overexpression of the multidrug resistance-associated protein (MRP1) gene
      encoding a human GS-X pump in cultured cells resulted in increased cellular
      resistance to antitumor agents, including doxorubicin (Dox) and daunomycin (Dau),
      as well as certain heavy metals. However, studies with membrane vesicles prepared
      from the resistant cells revealed that Dox and Dau are poor substrates for the
      transport mediated by MRP/GS-X pump, suggesting that metabolic modifications of
      these drugs might be required for the transport. To test this hypothesis, we
      prepared four glutathione conjugates by linking the cysteine residue of GSH to
      Dox and Dau at eitehr the C-7 or C-14 position. The affinity of the synthesized
      conjugates toward MRP/GS-X pump was examined in the LTC4 transport assay using
      membrane vesicles prepared from an MRP1 gene-overexpressing cell line, SR3A.
      Unconjugated Dox and Dau failed to inhibit the transport of LTC4, whereas 30
      microM GS-Dox or GS-Dau conjugates completely inhibited the transport. Kinetic
      analyses revealed that the inhibition by these GS-conjugates is competitive with
      Ki values ranging from 60 to 200 nM, suggesting that these compounds have high
      affinities toward MRP/GS-X pump and share the common binding site(s) with LTC4.
      Our present results support the hypothesis that glutathionation can facilitate
      the transport of anthracyclines by the MRP/GS-X pump.

PMID- 9647784
TI  - Cloning of cDNAs encoding porcine and human DNase II.
AB  - We report the molecular cloning of cDNAs encoding porcine and human DNase II and
      the genomic structure of the human DNase II gene. The full length cDNAs for
      porcine and human DNase II were isolated by polymerase chain reaction on the
      basis of amino acid sequences determined for the tryptic peptides of porcine
      liver DNase II. The porcine and human cDNAs contain 1095 and 1083 bp open reading
      frames, respectively, and encode 364 and 360 amino acid proteins with calculated
      molecular masses of 40,157 and 39,555, respectively. The amino acid sequencing of
      purified porcine DNase II reveals two N-termini with corresponding sequences
      present within the same open reading frame, suggesting proteolytic processing for
      the covalently bonded subunit structure of DNase II. Northern blot analysis
      demonstrated that a single transcript of 2.0 kb mRNA coding for DNase II is
      ubiquitously expressed in human tissues. A database search revealed that the
      human genomic sequence of chromosome 19p13.2 contains the DNase II gene.
      Characterization of the genomic sequence showed that the DNase II gene consists
      of six exons separated by five introns whose splice acceptor/donor sites agree
      with the GT/AG rule.

PMID- 9647786
TI  - Structural conservation in RNA loops III and VI of the internal ribosome entry
      sites of enteroviruses and rhinoviruses.
AB  - Alignment of the internal ribosome entry sites (IRES) of members of the
      Enteroviridae-Rhinoviridae (E/R) family reveals a consensus loop sequence of
      AANCCA closed by a C.G base pair. The consensus sequence was present in two
      distinct loops in domains III and VI. Four hairpins corresponding to the most
      common loop sequences, AAUCCA, AAACCA, GAACCA and AUCCA, were synthesized and
      studied by UV spectroscopy. Although all four oligomers had similar UV melting
      points their thermodynamic parameters revealed differing stabilities consistent
      with their loop size. Comparison of the aromatic proton and H1' chemical shifts
      for the four loop sequences obtained from this and our previous NMR study
      revealed strikingly similar trends. The pattern of chemical shifts suggest
      similar solution structures in spite of differences in sequence and loop size.
      This common structure provides a structural basis for their sequence conservation
      in E/R IRESes.

PMID- 9647785
TI  - Dermaseptin, a peptide antibiotic, stimulates microbicidal activities of
      polymorphonuclear leukocytes.
AB  - Dermaseptin (DRs S1), a 34-amino acid residue cationic antimicrobial peptide was
      studied for its effects on the production of reactive oxygen species (respiratory
      burst) and exocytosis of polymorphonuclear leukocytes (PMN). Treatment of PMN
      with DRs S1 (10-100 nM) stimulated significant production of reactive oxygen
      species (approximately a 2-fold increase relative to control) and release of
      myeloperoxidase. In addition, low DRs S1 concentrations (1-10 nM) primed the
      stimulation of respiratory burst induced by zymosan particles. In contrast to the
      native peptide, a dermaseptin fragment without either the COOH-terminal (DRs 1
      10) or NH2 terminal (DRs 16-34) portion was inactive. The DRs S1-induced
      respiratory burst was inhibited by a selective protein kinase C inhibitor, GF
      109203X, and was associated with early signalling events such as a rapid and
      transient elevation of cytosolic-free calcium concentration and phospholipase D
      activity. These data provide the first evidence of stimulating and priming
      properties of a peptide antibiotic on microbicidal activities of neutrophils,
      suggesting a potential role of dermaseptin in modulating host-defense mechanisms.

PMID- 9647787
TI  - High-affinity binding sites to the vitamin D receptor DNA binding domain in the
      human growth hormone promoter.
AB  - The regulation of the human growth hormone (hGH) gene by 1,25(OH)2D3 is a
      mechanism which is poorly understood. The objective of this study was to
      investigate whether the hGH gene has DNA recognition elements for the DNA binding
      domain of the vitamin D receptor. Using gel retardation assays and footprinting
      techniques, two high-affinity binding sites, denominated F1 and F2, were
      identified in the 5'-flanking sequence of hGH. The distal site, F1, located at 
      59 bp is made up of an imperfect direct repeat separated by 3 bp and showed a
      high degree of similarity with other known vitamin D response elements (VDREs).
      The proximal site, F2, located at -36 bp showed a single 7-bp sequence, which is
      different from other known VDREs. The location of both sites (F1 near the GHF
      1/Pit-1 response element, F2 contacting the TATA box) suggests that the vitamin D
      receptor by itself or through interference with other transcriptional factors may
      modulate hGH expression.

PMID- 9647788
TI  - Localization of RhoA GTPase to endothelial caveolae-enriched membrane domains.
AB  - Caveolae are small microdomains of the plasma membrane that are thought to play
      important roles in signal transduction processes. In this work, we have
      investigated the association of Rho proteins with caveolae-enriched membrane
      domains isolated from cultured endothelial cells. Fractionation of ECV304 cells
      by sucrose gradient density centrifugation in the absence of detergent resulted
      in the co-sedimentation of a significant proportion of RhoA and Cdc42 with known
      caveolae marker proteins, including caveolin, but not with other non-caveolae
      membrane proteins such as the angiotensin-converting enzyme. Immunoprecipitation
      experiments carried on crude endothelial cell lysates as well as with solubilized
      caveolae-enriched membrane domains showed the coimmunoprecipitation of caveolin
      with RhoA but not with Cdc42. Incubation of endothelial cell lysates with a
      glutathione-S-transferase (GST)-RhoA fusion protein resulted in the specific
      precipitation of caveolin, while addition of GST-caveolin-1 to the lysates
      promoted the precipitation of RhoA. Moreover, incubation of bacterially expressed
      RhoA with GST-caveolin-1 resulted in the precipitation of RhoA, indicating that
      RhoA directly interacts with caveolin-1. This interaction was found to be
      nucleotide-independent and was not affected by prior modification of RhoA with
      the C3 exoenzyme from C. botulinium or with the cytotoxic necrotinizing factor
      from E. coli. Taken together, these results suggest the association of RhoA with
      endothelial caveolae-enriched membrane domains, likely through physical
      interaction with caveolin-1. These findings may provide new insights into the
      functions played by Rho proteins and caveolae in signal transduction events.

PMID- 9647789
TI  - Highly specific and quantitative activation of STATs in 3T3-L1 adipocytes.
AB  - We have recently demonstrated that STATs 1, 3, 5A, 5B, and 6 are expressed in
      adipocytes. Using the 3T3-L1 cell line, we have examined the activation of all
      adipocyte expressed STATs by 23 different factors which are either potent
      regulators of adipocyte gene expression or known STAT activators in other cell
      types. STAT activation was assessed by examining nuclear translocation and
      tyrosine phosphorylation in serum deprived, fully differentiated 3T3-L1
      adipocytes. Unlike other adipocyte-expressed STATs, STAT 5A was present in the
      nucleus under basal conditions. Of all the activators examined, only growth
      hormone was capable of causing STATs 5A and 5B to translocate to the nucleus.
      None of the activators were capable of affecting the cellular distribution of
      STAT 6. Furthermore, our results indicate that there is a quantitative activation
      of STATs 1 and 3 by LIF, OSM, and IFN-gamma as measured by both nuclear
      translocation and tyrosine phosphorylation in whole cell extracts. IFN-gamma is a
      potent activator of STAT 1 and a weaker activator of STAT 3, whereas LIF and OSM
      are potent activators of STAT 3 and weaker activators of STAT 1. These studies
      demonstrate that STAT activation in adipocytes is highly specific, quantitative,
      and distinct.

PMID- 9647790
TI  - Ancient DNA in human bone remains from Pompeii archaeological site.
AB  - aDNA extraction and amplification procedures have been optimized for Pompeian
      human bone remains whose diagenesis has been determined by histological analysis.
      Single copy genes amplification (X and Y amelogenin loci and Y specific alphoid
      repeat sequences) have been performed and compared with anthropometric data on
      sexing.

PMID- 9647791
TI  - Demonstration of receptors specific for connective tissue growth factor on a
      human chondrocytic cell line (HCS-2/8).
AB  - The presence of receptors specific for connective tissue growth factor (CTGF) was
      demonstrated on a human chondrosarcoma-derived chondrocytic cell line, HCS-2/8.
      The binding of 125I-labeled recombinant CTGF to HCS-2/8 cells was inhibited by
      unlabeled CTGF but not by PDGF-BB or bFGF. Scatchard analysis revealed the
      presence of two classes of binding sites with Kd values of 18.6 and 259 nM on
      cells. A cross-linking study revealed the formation of 125I-CTGF-receptor complex
      with an apparent molecular weight of 280 kDa. The 125I-CTGF-receptor complex
      disappeared almost completely on the addition of unlabeled CTGF but not PDGF-BB
      or bFGF. In addition, the 125I-CTGF-receptor complex was immunoprecipitated with
      anti-CTGF antiserum but not with anti-PDGF receptor antiserum. These findings
      suggest that CTGF directly binds to specific receptor molecules on HCS-2/8 cells.

PMID- 9647795
TI  - Structure-activity study of the lantibiotic mutacin II from Streptococcus mutans
      T8 by a gene replacement strategy.
AB  - Mutacin II, elaborated by group II Streptococcus mutans, is a ribosomally
      synthesized and posttranslationally modified polypeptide antibiotic containing
      unusual thioether and didehydro amino acids. To ascertain the role of specific
      amino acid residues in mutacin II antimicrobial activity, we developed a
      streptococcal expression system that facilitates the replacement of the mutA gene
      with a single copy of a mutated variant gene. As a result, variants of mutacin II
      can be designed and expressed. The system was tested by constructing the
      following mutant peptides: delta N1, V7A, P9A, T10A, T10S, C15A, C26A, and C27A.
      All of these mutacin II variants except delta N1 and T10A, which were not
      secreted, were isolated, and their identities were verified by mass spectrometry.
      Variants P9A, C15A, C26A, and C27A failed to exert antimicrobial activity.
      Because the P9A and T10A variants comprise the "hinge" region of mutacin II,
      these observations suggest that in addition to the thioether and didehydro amino
      acids, the hinge region is essential for biological activity and biosynthesis or
      export of the peptide. Tandem mass spectrometry of the N-terminal part of the
      wild-type molecule and its C15A variant confirmed that the threonine at position
      10 is dehydrated and present as a didehydrobutyrine residue. This analysis of the
      active T10S variant further suggested that a didehydro amino acid at this
      position is specific for antimicrobial activity and that the biosynthetic
      machinery does not discriminate between threonine and serine. In contrast, the
      lack of production of mutacin variants with alanine substituted for threonine at
      position 10, as well as the deletion of asparagine at the N terminus (delta N1),
      indicates that specific residues in the propeptide may be crucial for certain
      steps in the biosynthetic pathway of this lantibiotic.

PMID- 9647796
TI  - Root colonization by Agrobacterium tumefaciens is reduced in cel, attB, attD, and
      attR mutants.
AB  - Root colonization by Agrobacterium tumefaciens was measured by using tomato and
      Arabidopsis thaliana roots dipped in a bacterial suspension and planted in soil.
      Wild-type bacteria showed extensive growth on tomato roots; the number of
      bacteria increased from 10(3) bacteria/cm of root length at the time of
      inoculation to more than 10(7) bacteria/cm after 10 days. The numbers of
      cellulose-minus and nonattaching attB, attD, and attR mutant bacteria were less
      than 1/10,000th the number of wild-type bacteria recovered from tomato roots. On
      roots of A. thaliana ecotype Landsberg erecta, the numbers of wild-type bacteria
      increased from about 30 to 8,000 bacteria/cm of root length after 8 days. The
      numbers of cellulose-minus and nonattaching mutant bacteria were 1/100th to
      1/10th the number of wild-type bacteria recovered after 8 days. The attachment of
      A. tumefaciens to cut A. thaliana roots incubated in 0.4% sucrose and observed
      with a light microscope was also reduced with cel and att mutants. These results
      suggest that cellulose synthesis and attachment genes play a role in the ability
      of the bacteria to colonize roots, as well as in bacterial pathogenesis.

PMID- 9647797
TI  - Epidemiological typing of Campylobacter isolates from meat processing plants by
      pulsed-field gel electrophoresis, fatty acid profile typing, serotyping, and
      biotyping.
AB  - Campylobacter spp. are a leading cause of bacterial gastroenteritis. Foods of
      animal origin, particularly under-cooked poultry, are common sources of
      Campylobacter species associated with disease in humans. A collection of 110
      Campylobacter jejuni and 31 C. coli human and environmental isolates from
      different Ontario, Canada, abattoirs were analyzed by pulsed-field gel
      electrophoresis, fatty acid profile typing, and biotyping. Previously collected
      serotyping data for the same isolates were also analyzed in this study. Pulsed
      field gel electrophoresis was found to be the most discriminatory of the typing
      methods, followed by serotyping, fatty acid profile typing, and biotyping. A wide
      variety of typing profiles were observed within the isolates, suggesting that
      several different Campylobacter sp. strains were present within the abattoirs.

PMID- 9647798
TI  - Degradation and Fate of Carbon Tetrachloride in Unadapted Methanogenic Granular
      Sludge.
AB  - The potential of granular sludge from upflow anaerobic sludge blanket (UASB)
      reactors for bioremediation of chlorinated pollutants was evaluated by using
      carbon tetrachloride (CT) as a model compound. Granular sludges cultivated in
      UASB reactors on methanol, a volatile fatty acid mixture, or sucrose readily
      degraded CT supplied at a concentration of 1,500 nmol/batch (approximately 10 uM)
      without any prior exposure to organohalogens. The maximum degradation rate was
      1.9 umol of CT g of volatile suspended solids-1 day-1. The main end products of
      CT degradation were CO2 and Cl-, and the yields of these end products were 44 and
      68%, respectively, of the initial amounts of [14C]CT and CT-Cl. Lower chlorinated
      methanes accumulated in minor amounts temporarily. Autoclaved (dead) sludges were
      capable of degrading CT at rates two- to threefold lower than those for living
      sludges, indicating that abiotic processes (mediated by cofactors or other sludge
      components) played an important role in the degradation observed. Reduced
      components in the autoclaved sludge were vital for CT degradation. A major part
      (51%) of the CT was converted abiotically to CS2. The amount of CO2 produced
      (23%) was lower and the amount of Cl- produced (86%) was slightly higher with
      autoclaved sludge than with living sludge. Both living and autoclaved sludges
      could degrade chloroform. However, only living sludge degraded dichloromethane
      and methylchloride. These results indicate that reductive dehalogenation, which
      was mediated better by living sludge than by autoclaved sludge, is only a minor
      pathway for CT degradation. The main pathway involves substitutive and oxidative
      dechlorination reactions that lead to the formation of CO2. Granular sludge,
      therefore, has outstanding potential for gratuitous dechlorination of CT to safe
      end products.

PMID- 9647799
TI  - Thermotoga neapolitana homotetrameric xylose isomerase is expressed as a
      catalytically active and thermostable dimer in Escherichia coli.
AB  - The xylA gene from Thermotoga neapolitana 5068 was expressed in Escherichia coli.
      Gel filtration chromatography showed that the recombinant enzyme was both a
      homodimer and a homotetramer, with the dimer being the more abundant form. The
      purified native enzyme, however, has been shown to be exclusively tetrameric. The
      two enzyme forms had comparable stabilities when they were thermoinactivated at
      95 degrees C. Differential scanning calorimetry revealed thermal transitions at
      99 and 109.5 degrees C for both forms, with an additional shoulder at 91 degrees
      C for the tetramer. These results suggest that the association of the subunits
      into the tetrameric form may have little impact on the stability and biocatalytic
      properties of the enzyme.

PMID- 9647800
TI  - Growth on urea can trigger death and peroxidation of the cyanobacterium
      Synechococcus sp. strain PCC 7002.
AB  - Laboratory conditions have been identified that cause the rapid death of cultures
      of cyanobacteria producing urease. Once the death phase had initiated in the
      stationary growth phase, cells were rapidly bleached of all pigmentation. Null
      mutations in the ureC gene, encoding the alpha subunit of urease, were
      constructed, and these mutants were no longer sensitive to growth in the presence
      of urea. High levels of peroxides, including lipid peroxides, were detected in
      the bleaching cells. Exogenously added polyunsaturated fatty acids triggered a
      similar death response. Vitamin E suppressed the formation of peroxides and
      delayed the onset of cell bleaching. The results suggest that these
      cyanobacterial cells undergo a metabolic imbalance that ultimately leads to
      oxidative stress and lipid peroxide formation. These observations may provide
      insights into the mechanism of sudden cyanobacterial bloom disappearance in
      nature.

PMID- 9647801
TI  - Isolation and entomotoxic properties of the Xenorhabdus nematophilus F1
      lecithinase.
AB  - Xenorhabdus spp. and Photorhabdus spp., entomopathogenic bacteria symbiotically
      associated with nematodes of the families Steinernematidae and Heterorhabditidae,
      respectively, were shown to produce different lipases when they were grown on
      suitable nutrient agar. Substrate specificity studies showed that Photorhabdus
      spp. exhibited a broad lipase activity, while most of the Xenorhabdus spp.
      secreted a specific lecithinase. Xenorhabdus spp. occur spontaneously in two
      variants, phase I and phase II. Only the phase I variants of Xenorhabdus
      nematophilus and Xenorhabdus bovienii strains produced lecithinase activity when
      the bacteria were grown on a solid lecithin medium (0.01% lecithin nutrient agar;
      24 h of growth). Five enzymatic isomers responsible for this activity were
      separated from the supernatant of a X. nematophilus F1 culture in two
      chromatographic steps, cation-exchange chromatography and C18 reverse-phase
      chromatography. The substrate specificity of the X. nematophilus F1 lecithinase
      suggested that a phospholipase C preferentially active on phosphatidylcholine
      could be isolated. The entomotoxic properties of each isomer were tested by
      injection into the hemocoels of insect larvae. None of the isomers exhibited
      toxicity with the insects tested, Locusta migratoria, Galleria mellonella,
      Spodoptera littoralis, and Manduca sexta. The possible role of lecithinase as
      either a virulence factor or a symbiotic factor is discussed.

PMID- 9647802
TI  - Analysis of molecular size distributions of cellulose molecules during hydrolysis
      of cellulose by recombinant Cellulomonas fimi beta-1,4-glucanases.
AB  - Four beta-1,4-glucanases (cellulases) of the cellulolytic bacterium Cellulomonas
      fimi were purified from Escherichia coli cells transformed with recombinant
      plasmids. Previous analyses using soluble substrates had suggested that CenA and
      CenC were endoglucanases while CbhA and CbhB resembled the exo-acting
      cellobiohydrolases produced by cellulolytic fungi. Analysis of molecular size
      distributions during cellulose hydrolysis by the individual enzymes confirmed
      these preliminary findings and provided further evidence that endoglucanase CenC
      has a more processive hydrolytic activity than CenA. The significant differences
      between the size distributions obtained during hydrolysis of bacterial
      microcrystalline cellulose and acid-swollen cellulose can be explained in terms
      of the accessibility of beta-1,4-glucan chains to enzyme attack. Endoglucanases
      and cellobiohydrolases were much more easily distinguished when the acid-swollen
      substrate was used.

PMID- 9647803
TI  - Molecular cloning, sequencing, and expression of a chemoreceptor gene from
      Leptospirillum ferrooxidans.
AB  - We have cloned and sequenced a 2,262-bp chromosomal DNA fragment from the
      chemolithoautotrophic acidophilic bacterium Leptospirillum ferrooxidans. This DNA
      contained an open reading frame for a 577-amino-acid protein showing several
      characteristics of the bacterial chemoreceptors and, therefore, we named this
      gene lcrI for Leptospirillum chemotaxis receptor I. This is the first sequence
      reported for a gene from L. ferrooxidans encoding a protein. The lcrI gene showed
      both sigma 28-like and sigma 70-like putative promoters. The LcrI deduced protein
      contained two hydrophobic regions most likely corresponding to the two
      transmembrane regions present in all of the methyl-accepting chemotaxis proteins
      (MCPs) which make them fold with both periplasmic and cytoplasmic domains. We
      have proposed a cytoplasmic domain for LcrI, which also contains the highly
      conserved domain (HCD region), present in all of the chemotactic receptors, and
      two probable methylation sites. The in vitro expression of a DNA plasmid
      containing the 2,262-bp fragment showed the synthesis of a 58-kDa protein which
      was immunoprecipitated by antibodies against the Tar protein (an MCP from
      Escherichia coli), confirming some degree of antigenic conservation. In addition,
      this 58-kDa protein was expressed in E. coli, being associated with its
      cytoplasmic membrane fraction. It was not possible to determine a chemotactic
      receptor function for LcrI expressed in E. coli. This was most likely due to the
      fact that the periplasmic pH of E. coli, which differs by 3 to 4 pH units from
      that of acidophilic chemolithotrophs, does not allow the right conformation for
      the LcrI periplasmic domain.

PMID- 9647804
TI  - Detoxification of Benzoxazolinone Allelochemicals from Wheat by Gaeumannomyces
      graminis var. tritici, G. graminis var. graminis, G. graminis var. avenae, and
      Fusarium culmorum.
AB  - The ability of phytopathogenic fungi to overcome the chemical defense barriers of
      their host plants is of great importance for fungal pathogenicity. We studied the
      role of cyclic hydroxamic acids and their related benzoxazolinones in plant
      interactions with pathogenic fungi. We identified species-dependent differences
      in the abilities of Gaeumannomyces graminis var. tritici, Gaeumannomyces graminis
      var. graminis, Gaeumannomyces graminis var. avenae, and Fusarium culmorum to
      detoxify these allelochemicals of gramineous plants. The G. graminis var.
      graminis isolate degraded benzoxazolin-2(3H)-one (BOA) and 6-methoxy-benzoxazolin
      2(3H)-one (MBOA) more efficiently than did G. graminis var. tritici and G.
      graminis var. avenae. F. culmorum degraded BOA but not MBOA. N-(2-Hydroxyphenyl)
      malonamic acid and N-(2-hydroxy-4-methoxyphenyl)-malonamic acid were the primary
      G. graminis var. graminis and G. graminis var. tritici metabolites of BOA and
      MBOA, respectively, as well as of the related cyclic hydroxamic acids. 2-Amino-3H
      phenoxazin-3-one was identified as an additional G. graminis var. tritici
      metabolite of BOA. No metabolite accumulation was detected for G. graminis var.
      avenae and F. culmorum by high-pressure liquid chromatography. The mycelial
      growth of the pathogenic fungi was inhibited more by BOA and MBOA than by their
      related fungal metabolites. The tolerance of Gaeumannomyces spp. for
      benzoxazolinone compounds is correlated with their detoxification ability. The
      ability of Gaeumannomyces isolates to cause root rot symptoms in wheat (cultivars
      Rektor and Astron) parallels their potential to degrade wheat allelochemicals to
      nontoxic compounds.

PMID- 9647805
TI  - Flow cytometry detection of infectious rotaviruses in environmental and clinical
      samples.
AB  - A method for the detection of infectious human rotaviruses based on infection of
      CaCo-2 cells and detection of infected cells by indirect immunofluorescence and
      flow cytometry (IIF-FC) has been developed. The technique was validated by
      performing a seminested reverse transcription-PCR assay with sorted cell
      populations. The efficiency of the procedure has been compared with that of the
      standard method of infection of MA104 cells and ulterior detection by IIF and
      optical microscopy (IIF-OM) and with that of infection of MA104 cells and
      detection by IIF-FC. The limit of sensitivity for the detection of the cell
      adapted strain Ito(r) P13, expressed as the most probable number of
      cytopathogenic units, was established as 200 and 2 for MA104 and CaCo-2 cells,
      respectively, by the IIF-FC method. The ratio of infectious virus particles to
      total virus particles for a wild-type rotavirus was determined to be 1/2 x 10(6)
      and 1/2 x 10(4) for IIF-OM with MA104 cells and IIF-FC with CaCo-2 cells,
      respectively. The use of IIF-FC with CaCo-2 cells was tested with fecal and water
      samples and proved to be more effective than the standard procedure for rotavirus
      detection.

PMID- 9647806
TI  - Atmospheric Methane Consumption by Forest Soils and Extracted Bacteria at
      Different pH Values.
AB  - The effect of pH on atmospheric methane (CH4) consumption was studied with
      slurries of forest soils and with bacteria extracted from the same soils. Soil
      samples were collected from a mixed hardwood stand in New Hampshire, from
      jackpine and aspen stands at the BOREAS (Boreal Ecosystem Atmosphere Study) site
      near Thompson, northern Manitoba, from sites in southern Quebec, including a
      beech stand and a meadow, and from a site in Ontario (cultivated humisol).
      Consumption of atmospheric CH4 (concentration, approximately 1.8 ppm) occurred at
      depths of >5 cm in both acidic (pH 4.5 to 5.2) and alkaline (pH 7.2 to 7.8)
      soils. In slurries of acidic soils, maximum activity occurred at different pH
      values (pH 4.0 to 6.5). Bacteria extracted from these soils by high-speed
      blending and density gradient centrifugation showed pH responses different from
      the pH responses of the slurries. In all cases, these bacteria had a
      methanotrophy pH optimum of 5.8 and exhibited no activity at pH 6.8 to 7.0, the
      pH optimum range for known methanotrophs. This difference in pH responses could
      be useful in modifying media currently used for isolation of these organisms.
      Methanotrophic activity was induced in previously non-CH4-consuming soils by
      preincubation with 5% (vol/vol) CH4 (50,000 ul of CH4 per liter) or by liquid
      enrichment with 20% CH4. The bacteria showed pH responses typical of known
      methanotrophs and not typical of preexisting consumers of ambient CH4.
      Furthermore, methanotrophs induced by high CH4 levels were more readily extracted
      from soil than preexisting ambient CH4 consumers were. In the alkaline soils,
      preexisting activity either was destroyed or resisted extraction by the procedure
      used. The results support the hypothesis that consumers of ambient CH4 in soils
      are physiologically distinct from the known methanotrophs.

PMID- 9647807
TI  - Heterologous protein secretion directed by a repressible acid phosphatase system
      of Kluyveromyces lactis: characterization of upstream region-activating sequences
      in the KIPHO5 gene.
AB  - Transcription of the repressible acid phosphatase gene (KIPHO5) in Kluyveromyces
      lactis is strongly regulated in response to the level of inorganic phosphate (Pi)
      present in the growth medium. We have begun a study of the promoter region of
      this gene in order to identify sequences involved in the phosphate control of
      KIPHO5 expression and to design new expression-secretion systems in K. lactis.
      Deletion analysis and directed mutagenesis revealed two major identical upstream
      activating sequences (UAS) CACGTG at positions -430 (USA1) and -192 (UAS2)
      relative to the ATG initiation codon. These sequences are identical to those
      described for Saccharomyces cerevisiae for the binding of Pho4p. Deletion or
      directed mutagenesis of either one or both UAS reduce KIPHO5 expression by the
      same amount (approximately 80%). When fused to the coding region of trout growth
      hormone cDNA (tGH-II), the promoter and signal peptide-encoding region of the
      phosphate-repressible KIPHO5 gene drives the expression of this gene and the
      secretion of the tGHII protein. Synthesis of tGHIIp in K. lactis transformants
      carrying this construct was found to be regulated by the Pi present in the
      medium; depression of heterologous protein expression can therefore be achieved
      by lowering the Pi concentration.

PMID- 9647808
TI  - Role of Organic Acids in the Manganese-Independent Biobleaching System of
      Bjerkandera sp. Strain BOS55
AB  - Bjerkandera sp. strain BOS55 is a white rot fungus that can bleach EDTA-extracted
      eucalyptus oxygen-delignified kraft pulp (OKP) without any requirement for
      manganese. Under manganese-free conditions, additions of simple physiological
      organic acids (e.g., glycolate, glyoxylate, oxalate, and others) at 1 to 5 mM
      stimulated brightness gains and pulp delignification two- to threefold compared
      to results for control cultures not receiving acids. The role of the organic
      acids in improving the manganese-independent biobleaching was shown not to be due
      to pH-buffering effects. Instead, the stimulation was attributed to enhanced
      production of manganese peroxidase (MnP) and lignin peroxidase (LiP) as well as
      increased physiological concentrations of veratryl alcohol and oxalate. These
      factors contributed to greatly improved production of superoxide anion radicals,
      which may have accounted for the more extensive biobleaching. Optimum
      biobleaching corresponded most to the production of MnP. These results suggest
      that MnP from Bjerkandera is purposefully produced in the absence of manganese
      and can possibly function independently of manganese in OKP delignification. LiP
      probably also contributed to OKP delignification when it was present.

PMID- 9647809
TI  - Differentiation of Lactobacillus Species by Molecular Typing.
AB  - A total of 64 type, reference, clinical, health food, and stock isolates of
      microaerophilic Lactobacillus species were examined by restriction fragment
      length polymorphisms. Of particular interest were members of six of the eight
      species most commonly recovered from the vaginas of healthy premenopausal women,
      namely, Lactobacillus jensenii, L. casei, L. rhamnosus, L. acidophilus, L.
      plantarum, and L. fermentum. Six main groupings were identified on the basis of
      ribotyping. This technique was able to classify fresh isolates to the species
      level. In the case of the ribotype A grouping for L. rhamnosus, differences
      between strains were evident by chromosome typing (chromotyping). Many isolates
      did not possess plasmids. Six L. rhamnosus strains isolated from four different
      health food products appeared to be identical to L. rhamnosus ATCC 21052. The
      molecular typing system is useful for identifying and differentiating
      Lactobacillus isolates. Studies of strains of potential importance to the
      urogenital flora should include molecular characterization as a means of
      comparing genetic traits with those of strains whose characteristics associated
      with colonization and antagonism against pathogens have been defined.

PMID- 9647810
TI  - Cloning and characterization of the lactococcal plasmid-encoded type II
      restriction/modification system, LlaDII.
AB  - The LlaDII restriction/modification (R/M) system was found on the naturally
      occurring 8.9-kb plasmid pHW393 in Lactococcus lactis subsp. cremoris W39. A 2.4
      kb PstI-EcoRI fragment inserted into the Escherichia coli-L. lactis shuttle
      vector pCI3340 conferred to L. lactis LM2301 and L. lactis SMQ86 resistance
      against representatives of the three most common lactococcal phage species: 936,
      P335, and c2. The LlaDII endonuclease was partially purified and found to
      recognize and cleave the sequence 5'-GC decreases NGC-3', where the arrow
      indicates the cleavage site. It is thus an isoschizomer of the commercially
      available restriction endonuclease Fnu4HI. Sequencing of the 2.4-kb PstI-EcoRI
      fragment revealed two open reading frames arranged tandemly and separated by a
      105-bp intergenic region. The endonuclease gene of 543 bp preceded the methylase
      gene of 954 bp. The deduced amino acid sequence of the LlaDII R/M system showed
      high homology to that of its only sequenced isoschizomer, Bsp6I from Bacillus sp.
      strain RFL6, with 41% identity between the endonucleases and 60% identity between
      the methylases. The genetic organizations of the LlaDII and Bsp6I R/M systems are
      identical. Both methylases have two recognition sites (5'-GCGGC-3' and 5'-GCCGC
      3') forming a putative stemloop structure spanning part of the presumed -35
      sequence and part of the intervening region between the -35 and -10 sequences.
      Alignment of the LlaDII and Bsp6I methylases with other m5C methylases showed
      that the protein primary structures possessed the same organization.

PMID- 9647811
TI  - Isolation and characterization of phenol-degrading denitrifying bacteria.
AB  - Phenol is a man-made as well as a naturally occurring aromatic compound and an
      important intermediate in the biodegradation of natural and industrial aromatic
      compounds. Whereas many microorganisms that are capable of aerobic phenol
      degradation have been isolated, only a few phenol-degrading anaerobic organisms
      have been described to date. In this study, three novel nitrate-reducing
      microorganisms that are capable of using phenol as a sole source of carbon were
      isolated and characterized. Phenol-degrading denitrifying pure cultures were
      obtained by enrichment culture from anaerobic sediments obtained from three
      different geographic locations, the East River in New York, N.Y., a Florida
      orange grove, and a rain forest in Costa Rica. The three strains were shown to be
      different from each other based on physiologic and metabolic properties. Even
      though analysis of membrane fatty acids did not result in identification of the
      organisms, the fatty acid profiles were found to be similar to those of Azoarcus
      species. Sequence analysis of 16S ribosomal DNA also indicated that the phenol
      degrading isolates were closely related to members of the genus Azoarcus. The
      results of this study add three new members to the genus Azoarcus, which
      previously comprised only nitrogen-fixing species associated with plant roots and
      denitrifying toluene degraders.

PMID- 9647812
TI  - Cytoplasmic membrane lipoprotein LppC of Streptococcus equisimilis functions as
      an acid phosphatase.
AB  - The function of the streptococcal cytoplasmic membrane lipoprotein, LppC, was
      identified with isogenic Streptococcus equisimilis H46A and Escherichia coli
      JM109 strain pairs differing in whether they contained [H46A and JM109(pLPP2)] or
      lacked (H46A lppC::pLPP10 and JM109) the functional lppC gene for comparative
      phosphatase determinations under acidic conditions. lppC-directed acid
      phosphatase activity was demonstrated zymographically and by specific enzymatic
      activity assays, with whole cells or cell membrane preparations as enzyme
      sources. LppC acid phosphatase showed optimum activity at pH 5, and the enzyme
      activity was unaffected by Triton X-100, L-(+)-tartaric acid, or EDTA. Database
      searches revealed significant structural homology of LppC to the Streptococcus
      pyogenes LppA, Flavobacterium meningosepticum OplA, Helicobacter pylori HP1285,
      and Haemophilus influenzae Hel [e (P4)] proteins. These results suggest a
      possible function for these proteins and establish a novel function of
      streptococcal cell membrane lipoproteins.

PMID- 9647813
TI  - Abundance in sewage of bacteriophages that infect Escherichia coli O157:H7 and
      that carry the Shiga toxin 2 gene.
AB  - Shiga toxin-converting bacteriophages are involved in the pathogenicity of some
      enteric bacteria, such as Escherichia coli O157:H7, but data on the occurrence
      and distribution of such phages as free particles in nature were not available.
      An experimental approach has been developed to detect the presence of the Shiga
      toxin 2 (Stx 2)-encoding bacteriophages in sewage. The Stx 2 gene was amplified
      by PCR from phages concentrated from 10-ml samples of sewage. Moreover, the
      phages carrying the Stx 2 gene were detected in supernatants from bacteriophage
      enrichment cultures by using an Stx 2-negative E. coli O157:H7 strain infected
      with phages purified from volumes of sewage as small as 0.02 ml. Additionally,
      the A subunit of Stx 2 was detected in the supernatants of the bacteriophage
      enrichment cultures, which also showed cytotoxic activity for Vero cells. By
      enrichment of phages concentrated from different volumes of sewage and applying
      the most-probable-number technique, it was estimated that the number of phages
      infectious for E. coli O157:H7 and carrying the Stx 2 gene was in the range of 1
      to 10 per ml of sewage from two different origins. These values were
      approximately 1% of all phages infecting E. coli O157:H7.

PMID- 9647814
TI  - Detection of hemolysin variants of Shiga toxin-producing Escherichia coli by PCR
      and culture on vancomycin-cefixime-cefsulodin blood agar.
AB  - The presence of a hemolysin-encoding gene, elyA or hlyA, from Shiga toxin
      producing Escherichia coli (STEC) was detected by PCR in each of 95 strains
      tested. PCR products of elyA from human STEC isolates of serovars frequently
      detected in Germany, such as O157:H-, O103:H2, O103:H-, O26:H11, and O26:H-,
      showed nucleotide sequences identical to previously reported ones for O157:H7 and
      O111:H- strains. Compared to them, four elyA amplicons derived from human
      isolates of rare STEC serovars showed identity of about 98% but lacked an AluI
      restriction site. However, the nucleotide sequence of an amplicon derived from a
      porcine O138:K81:H- STEC strain was identical to the corresponding region of
      hlyA, encoding alpha-hemolysin, from E. coli. This hlyA amplicon showed 68%
      identity with the nucleotide sequence of the corresponding elyA fragment. It
      differed from the elyA PCR product in restriction fragments generated by AluI,
      EcoRI, and MluI. Of the 95 representative STEC strains, 88 produced hemolysin on
      blood agar supplemented with vancomycin (30 mg/liter), cefixime (20
      micrograms/liter), and cefsulodin (3 mg/liter) (BVCC). The lowest added numbers
      of two to six STEC CFU per g of stool or per ml of raw milk were detectable on
      BVCC plates after seeding of the preenrichment broth, modified tryptic soy broth
      (mTSB) supplemented with novobiocin (10 mg/liter), with 16 STEC strains. These
      strains represented the seven prevailing serovars diagnosed from German patients.
      However, with ground-beef samples, PCR was essential to identify the lowest added
      numbers of two to six STEC CFU among colonies of hemolyzing Enterobacteriaceae,
      such as Serratia spp. and alpha-hemolysin-producing E. coli. We conclude that
      preenrichment of stool and food samples in mTSB for 6 h followed by overnight
      culturing on BVCC is a simple method for the isolation and presumptive
      identification of STEC.

PMID- 9647815
TI  - Construction and use of an ipb DNA module to generate Pseudomonas strains with
      constitutive trichloroethene and isopropylbenzene oxidation activity.
AB  - Pseudomonas sp. strain JR1 exhibits trichloroethene (TCE) oxidation activity with
      isopropylbenzene (IPB) as the inducer substrate. We previously reported the genes
      encoding the first three enzymes of the IPB-degradative pathway (ipbA1, ipbA2,
      ipbA3, ipbA4, ipbB, and ipbC) and identified the initial IPB dioxygenase (IpbA1
      A2A3A4) as responsible for TCE cooxidation (U. Pflugmacher, B. Averhoff, and G.
      Gottschalk, Appl. Environ. Microbiol. 62:3967-3977, 1996). Primer extension
      analyses revealed multiple transcriptional start points located upstream of the
      translational initiation codon of ipbA1. The transcription from these start sites
      was found to be IPB dependent. Thirty-one base pairs upstream of the first
      transcriptional start point tandemly repeated DNA sequences overlapping the -35
      region of a putative sigma 70 promoter were found. These repeats exhibit
      significant sequence similarity to the operator-promoter region of the xyl meta
      operon in Pseudomonas putida, which is required for the binding of XylS, a
      regulatory protein of the XylS (also called AraC) family. These similarities
      suggest that the transcription of the IPB dioxygenase genes is modulated by a
      regulatory protein of the XylS/AraC family. The construction of an ipb DNA module
      devoid of this ipb operator-promoter region and the stable insertion of this DNA
      module into the genomes of different Pseudomonas strains resulted in pseudomonads
      with constitutive IPB and TCE oxidation activities. Constitutive TCE oxidation of
      two such Pseudomonas hybrid strains, JR1A::ipb and CBS-3::ipb, was found to be
      stable for more than 120 generations in antibiotic-free medium. Evaluation of
      constitutive TCE degradation rates revealed that continuous cultivation of strain
      JR1A::ipb resulted in a significant increase in rates of TCE degradation.

PMID- 9647816
TI  - Small-Scale DNA Sample Preparation Method for Field PCR Detection of Microbial
      Cells and Spores in Soil.
AB  - Efficient, nonselective methods to obtain DNA from the environment are needed for
      rapid and thorough analysis of introduced microorganisms in environmental samples
      and for analysis of microbial community diversity in soil. A small-scale
      procedure to rapidly extract and purify DNA from soils was developed for in-the
      field use. Amounts of DNA released from bacterial vegetative cells, bacterial
      endospores, and fungal conidia were compared by using hot-detergent treatment,
      freeze-thaw cycles, and bead mill homogenization. Combining a hot-detergent
      treatment with bead mill homogenization gave the highest DNA yields from all
      three microbial cell types and provided DNA from the broadest range of microbial
      groups in a natural soil community. Only the bead mill homogenization step was
      effective for DNA extraction from Bacillus globigii (B. subtilis subsp. niger)
      endospores or Fusarium moniliforme conidia. The hot-detergent-bead mill procedure
      was simplified and miniaturized. By using this procedure and small-scale, field
      adapted purification and quantification procedures, DNA was prepared from four
      different soils seeded with Pseudomonas putida cells or B. globigii spores. In a
      New Mexico soil, seeded bacterial targets were detected with the same sensitivity
      as when assaying pure bacterial DNA (2 to 20 target gene copies in a PCR
      mixture). The detection limit of P. putida cells and B. globigii spores in
      different soils was affected by the amount of background DNA in the soil samples,
      the physical condition of the DNA, and the amount of DNA template used in the
      PCR.

PMID- 9647817
TI  - Molecular cloning, nucleotide sequence, and expression in Escherichia coli of a
      hemolytic toxin (aerolysin) gene from Aeromonas trota.
AB  - Aeromonas trota AK2, which was derived from ATCC 49659 and produces the
      extracellular pore-forming hemolytic toxin aerolysin, was mutagenized with the
      transposon mini-Tn5Km1 to generate a hemolysin-deficient mutant, designated
      strain AK253. Southern blotting data indicated that an 8.7-kb NotI fragment of
      the genomic DNA of strain AK253 contained the kanamycin resistance gene of mini
      Tn5Km1. The 8.7-kb NotI DNA fragment was cloned into the vector pGEM5Zf(-) by
      selecting for kanamycin resistance, and the resultant clone, pAK71, showed
      aerolysin activity in Escherichia coli JM109. The nucleotide sequence of the aerA
      gene, located on the 1.8-kb ApaI-EcoRI fragment, was determined to consist of
      1,479 bp and to have an ATG initiation codon and a TAA termination codon. An in
      vitro coupled transcription-translation analysis of the 1.8-kb region suggested
      that the aerA gene codes for a 54-kDa protein, in agreement with nucleotide
      sequence data. The deduced amino acid sequence of the aerA gene product of A.
      trota exhibited 99% homology with the amino acid sequence of the aerA product of
      Aeromonas sobria AB3 and 57% homology with the amino acid sequences of the
      products of the aerA genes of Aeromonas salmonicida 17-2 and A. sobria 33.

PMID- 9647818
TI  - A two-component monooxygenase catalyzes both the hydroxylation of p-nitrophenol
      and the oxidative release of nitrite from 4-nitrocatechol in Bacillus sphaericus
      JS905.
AB  - Bacteria that metabolize p-nitrophenol (PNP) oxidize the substrate to 3
      ketoadipic acid via either hydroquinone or 1,2,4-trihydroxybenzene (THB);
      however, initial steps in the pathway for PNP biodegradation via THB are unclear.
      The product of initial hydroxylation of PNP could be either 4-nitrocatechol or 4
      nitroresorcinol. Here we describe the complete pathway for aerobic PNP
      degradation by Bacillus sphaericus JS905 that was isolated by selective
      enrichment from an agricultural soil in India. Washed cells of PNP-grown JS905
      released nitrite in stoichiometric amounts from PNP and 4-nitrocatechol.
      Experiments with extracts obtained from PNP-grown cells revealed that the initial
      reaction is a hydroxylation of PNP to yield 4-nitrocatechol. 4-Nitrocatechol is
      subsequently oxidized to THB with the concomitant removal of the nitro group as
      nitrite. The enzyme that catalyzed the two sequential monooxygenations of PNP was
      partially purified and separated into two components by anion-exchange
      chromatography and size exclusion chromatography. Both components were required
      for NADH-dependent oxidative release of nitrite from PNP or 4-nitrocatechol. One
      of the components was identified as a reductase based on its ability to catalyze
      the NAD(P)H-dependent reduction of 2,6-dichlorophenolindophenol and nitroblue
      tetrazolium. Nitrite release from either PNP or 4-nitrocatechol was inhibited by
      the flavoprotein inhibitor methimazole. Our results indicate that the two
      monooxygenations of PNP to THB are catalyzed by a single two-component enzyme
      system comprising a flavoprotein reductase and an oxygenase.

PMID- 9647819
TI  - Glutamate Biosynthesis in Lactococcus lactis subsp. lactis NCDO 2118
AB  - Unlike other lactic acid bacteria, Lactococcus lactis subsp. lactis NCDO 2118 was
      able to grow in a medium lacking glutamate and the amino acids of the glutamate
      family. Growth in such a medium proceeded after a lag phase of about 2 days and
      with a reduced growth rate (0.11 h-1) compared to that in the reference medium
      containing glutamate (0.16 h-1). The enzymatic studies showed that a
      phosphoenolpyruvate carboxylase activity was present, while the malic enzyme and
      the enzymes of the glyoxylic shunt were not detected. As in most anaerobic
      bacteria, no alpha-ketoglutarate dehydrogenase activity could be detected, and
      the citric acid cycle was restricted to a reductive pathway leading to succinate
      formation and an oxidative branch enabling the synthesis of alpha-ketoglutarate.
      The metabolic bottleneck responsible for the limited growth rate was located in
      this latter pathway. As regards the synthesis of glutamate from alpha
      ketoglutarate, no glutamate dehydrogenase was detected. While the glutamate
      synthase-glutamine synthetase system was detected at a low level, high
      transaminase activity was measured. The conversion of alpha-ketoglutarate to
      glutamate by the transaminase, the reverse of the normal physiological direction,
      operated with different amino acids as nitrogen donor. All of the enzymes assayed
      were shown to be constitutive.

PMID- 9647820
TI  - Construction and expression of a bifunctional single-chain antibody against
      Bacillus cereus p6ores.
AB  - The variable-region genes of monoclonal antibody against Bacillus cereus spores
      were cloned from mouse hybridoma cells by reverse transcription-PCR. The heavy-
      and light-chain variable-region genes were connected by a 45-base linker DNA to
      allow folding of the fusion protein into a functional tertiary structure. For
      detection of protein expression, a 10-amino-acid strep tag (biotin-like peptide)
      was attached to the C terminus of recombinant antibody as the reporter peptide.
      The single-chain antibody construct was inserted into the expression vector and
      expressed in Escherichia coli under the control of the T7 RNA polymerase-T7
      promoter expression system. The expressed single-chain antibody was detected on
      Western blots by using a streptavidin-conjugated enzyme system. This small
      recombinant antibody fragment (ca. 28,000 Da by calculation) had B. cereus spore
      binding ability and antigen specificity similar to those of its parent native
      monoclonal antibody.

PMID- 9647821
TI  - Development of a streptavidin-conjugated single-chain antibody that binds
      Bacillus cereus spores.
AB  - Control of microorganisms such as Bacillus cereus spores is critical to ensure
      the safety and a long shelf life of foods. A bifunctional single chain antibody
      has been developed for detection and binding of B. cereus T spores. The genes
      that encode B. cereus T spore single-chain antibody and streptavidin were
      connected for use in immunoassays and immobilization of the recombinant
      antibodies. A truncated streptavidin, which is smaller than but has biotin
      binding ability similar to that of streptavidin, was used as the affinity domain
      because of its high and specific affinity with biotin. The fusion protein gene
      was expressed in Escherichia coli BL21 (DE3) with the T7 RNA polymerase-T7
      promoter expression system. Immunoblotting revealed an antigen specificity
      similar to that of its parent native monoclonal antibody. The single-chain
      antibody-streptavidin fusion protein can be used in an immunoassay of B. cereus
      spores by applying a biotinylated enzyme detection system. The recombinant
      antibodies were immobilized on biotinylated magnetic beads by taking advantage of
      the strong biotin-streptavidin affinity. Various liquids were artificially
      contaminated with 5 x 10(4) B. cereus spores per ml. Greater than 90% of the B.
      cereus spores in phosphate buffer or 37% of the spores in whole milk were tightly
      bound and removed from the liquid phase by the immunomagnetic beads.

PMID- 9647822
TI  - Quantification of Gordona amarae strains in foaming activated sludge and
      anaerobic digester systems with oligonucleotide hybridization probes.
AB  - Previous studies have shown the predominance of mycolic acid-containing
      filamentous actinomycetes (mycolata) in foam layers in activated sludge systems.
      Gordona (formerly Nocardia) amarae often is considered the major representative
      of this group in activated sludge foam. In this study, small-subunit rRNA genes
      of four G. amarae strains were sequenced, and the resulting sequences were
      compared to the sequence of G. amarae type strain SE-6. Comparative sequence
      analysis showed that the five strains used represent two lines of evolutionary
      descent; group 1 consists of strains NM23 and ASAC1, and group 2 contains strains
      SE-6, SE-102, and ASF3. The following three oligonucleotide probes were designed:
      a species-specific probe for G. amarae, a probe specific for group 1, and a probe
      targeting group 2. The probes were characterized by dissociation temperature and
      specificity studies, and the species-specific probe was evaluated for use in
      fluorescent in situ hybridizations. By using the group-specific probes, it was
      possible to place additional G. amarae isolates in their respective groups. The
      probes were used along with previously designed probes in membrane hybridizations
      to determine the abundance of G. amarae, group 1, group 2, bacterial, mycolata,
      and Gordona rRNAs in samples obtained from foaming activated sludge systems in
      California, Illinois, and Wisconsin. The target groups were present in
      significantly greater concentrations in activated sludge foam than in mixed
      liquor and persisted in anaerobic digesters. Hybridization results indicated that
      the presence of certain G. amarae strains may be regional or treatment plant
      specific and that previously uncharacterized G. amarae strains may be present in
      some systems.

PMID- 9647823
TI  - Sequencing and characterization of the xyl operon of a gram-positive bacterium,
      Tetragenococcus halophila.
AB  - The xyl operon of a gram-positive bacterium, Tetragenococcus halophila
      (previously called Pediococcus halophilus), was cloned and sequenced. The DNA was
      about 7.7 kb long and contained genes for a ribose binding protein and part of a
      ribose transporter, xylR (a putative regulatory gene), and the xyl operon, along
      with its regulatory region and transcription termination signal, in this order.
      The DNA was AT rich, the GC content being 35.8%, consistent with the GC content
      of this gram-positive bacterium. The xyl operon consisted of three genes, xylA,
      encoding a xylose isomerase, xylB, encoding a xylulose kinase, and xylE, encoding
      a xylose transporter, with predicted molecular weights of 49,400, 56,400, and
      51,600, respectively. The deduced amino acid sequences of the XylR, XylA, XylB,
      and XylE proteins were similar to those of the corresponding proteins in other
      gram-positive and -negative bacteria, the similarities being 37 to 64%. Each
      polypeptide of XylB and XylE was expressed functionally in Escherichia coli. XylE
      transported D-xylose in a sodium ion-dependent manner, suggesting that it is the
      first described xylose/Na+ symporter. The XylR protein contained a consensus
      sequence for binding catabolites of glucose, such as glucose-6-phosphate, which
      has been discovered in glucose and fructose kinases in bacteria. Correspondingly,
      the regulatory region of this operon contained a putative binding site of XylR
      with a palindromic structure. Furthermore, it contained a consensus sequence, CRE
      (catabolite-responsive element), for binding CcpA (catabolite control protein A).
      We speculate that the transcriptional regulation of this operon resembles the
      regulation of catabolite-repressible operons such as the amy, lev, xyl, and gnt
      operons in various gram-positive bacteria. We discuss the significance of the
      regulation of gene expression of this operon in T. halophila.

PMID- 9647824
TI  - Cloning of a Sphingomonas paucimobilis SYK-6 gene encoding a novel oxygenase that
      cleaves lignin-related biphenyl and characterization of the enzyme.
AB  - Sphingomonas paucimobilis SYK-6 transforms 2,2'-dihydroxy-3,3'-dimethoxy-5,5'
      dicarboxybiphenyl (DDVA), a lignin-related biphenyl compound, to 5
      carboxyvanillic acid via 2,2',3-trihydroxy-3'-methoxy-5,5'-dicarboxybiphenyl (OH
      DDVA) as an intermediate (15). The ring fission of OH-DDVA is an essential step
      in the DDVA degradative pathway. A 15-kb EcoRI fragment isolated from the cosmid
      library complemented the growth deficiency of a mutant on OH-DDVA. Subcloning and
      deletion analysis showed that a 1.4-kb DNA fragment included the gene responsible
      for the ring fission of OH-DDVA. An open reading frame encoding 334 amino acids
      was identified and designated ligZ. The deduced amino acid sequence of LigZ had
      18 to 21% identity with the class III extradiol dioxygenase family, including the
      beta subunit (LigB) of protocatechuate 4,5-dioxygenase of SYK-6 (Y. Noda, S.
      Nishikawa, K.-I. Shiozuka, H. Kadokura, H. Nakajima, K. Yano, Y. Katayama, N.
      Morohoshi, T. Haraguchi, and M. Yamasaki, J. Bacteriol. 172:2704-2709, 1990),
      catechol 2,3-dioxygenase I (MpcI) of Alcaligenes eutrophus JMP222 (M. Kabisch and
      P. Fortnagel, Nucleic Acids Res. 18:3405-3406, 1990), the catalytic subunit of
      the meta-cleavage enzyme (CarBb) for 2'-aminobiphenyl-2,3-diol from Pseudomonas
      sp. strain CA10 (S. I. Sato, N. Ouchiyama, T. Kimura, H. Nojiri, H. Yamane, and
      T. Omori, J. Bacteriol. 179:4841-4849, 1997), and 2,3-dihydroxyphenylpropionate
      1,2-dioxygenase (MhpB) of Escherichia coli (E. L. Spence, M. Kawamukai, J.
      Sanvoisin, H. Braven, and T. D. H. Bugg, J. Bacteriol. 178:5249-5256, 1996). The
      ring fission product formed from OH-DDVA by LigZ developed a yellow color with an
      absorption maximum at 455 nm, suggesting meta cleavage. Thus, LigZ was concluded
      to be a ring cleavage extradiol dioxygenase. LigZ activity was detected only for
      OH-DDVA and 2,2',3,3'-tetrahydroxy-5,5'-dicarboxybiphenyl and was dependent on
      the ferrous ion.

PMID- 9647825
TI  - Molecular Analysis of Bacterial Communities in a Three-Compartment Granular
      Activated Sludge System Indicates Community-Level Control by Incompatible
      Nitrification Processes.
AB  - Bacterial community structure and the predominant nitrifying activities and
      populations in each compartment of a three-compartment activated sludge system
      were determined. Each compartment was originally inoculated with the same
      activated sludge community entrapped in polyethylene glycol gel granules, and
      ammonium nitrogen was supplied to the system in an inorganic salts solution at a
      rate of 5.0 g of N liter of granular activated sludge-1 day-1. After 150 days of
      operation, the system was found to comprise a series of sequential nitrifying
      reactions (K. Noto, T. Ogasawara, Y. Suwa, and T. Sumino, Water Res. 32:769-773,
      1998), presumably mediated by different bacterial populations. Activity data
      showed that all NH4-N was completely oxidized in compartments one and two
      (approximately half in each), but no significant nitrite oxidation was observed
      in these compartments. In contrast, all available nitrite was oxidized to nitrate
      in compartment three. To study the microbial populations and communities in this
      system, total bacterial DNA isolated from each compartment was analyzed for
      community structure based on the G+C contents of the component populations.
      Compartment one showed dominant populations having 50 and 67% G+C contents.
      Compartment two was similar in structure to compartment one. The bacterial
      community in compartment three had dominant populations with 62 and 67% G+C
      contents and retained the 50% G+C content population only at a greatly diminished
      level. The 50% G+C content population from compartment one hybridized strongly
      with amo (ammonia monooxygenase) and hao (hydroxylamine oxidoreductase) gene
      probes from Nitrosomonas europaea. However, the 50% G+C content population from
      compartment two hybridized strongly with the hao probe but only weakly with the
      amo probe, suggesting that the predominant ammonia-oxidizing populations in
      compartments one and two might be different. Since different activities and
      populations come to dominate in each compartment from an identical inoculum, it
      appears that the nitrification processes may be somewhat incompatible, resulting
      in a series of sequential reactions and different communities in this three
      compartment system.

PMID- 9647826
TI  - Kinetic Parameters of Denitrification in a River Continuum.
AB  - Kinetic parameters for nitrate reduction in intact sediment cores were
      investigated by using the acetylene blockage method at five sites along the Swale
      Ouse river system in northeastern England, including a highly polluted tributary,
      R. Wiske. The denitrification rate in sediment containing added nitrate exhibited
      a Michaelis-Menten-type curve. The concentration of nitrate for half-maximal
      activity (Kmap) by denitrifying bacteria increased on passing downstream from
      13.1 to 90.4 uM in the main river, but it was highest (640 uM) in the Wiske. The
      apparent maximal rate (Vmaxap) ranged between 35.8 and 324 umol of N m-2 h-1 in
      the Swale-Ouse (increasing upstream to downstream), but it was highest in the
      Wiske (1,194 umol N m-2 h-1). A study of nitrous oxide (N2O) production at the
      same time showed that rates ranged from below the detection limit (0.05 umol of
      N2O-N m-2 h-1) at the headwater site to 27 umol of N2O-N m-2 h-1 at the
      downstream site. In the Wiske the rate was up to 570 umol of N2O-N m-2 h-1,
      accounting for up to 80% of total N gas production.

PMID- 9647827
TI  - Increase in Endogenous and Exogenous Cyclic AMP Levels Inhibits Sclerotial
      Development in Sclerotinia sclerotiorum.
AB  - Growth and development of a wild-type Sclerotinia sclerotiorum isolate were
      examined in the presence of various pharmacological compounds to investigate
      signal transduction pathways that influence the development of sclerotia.
      Compounds known to increase endogenous cyclic AMP (cAMP) levels in other
      organisms by inhibiting phosphodiesterase activity (caffeine and 3-isobutyl-1
      methyl xanthine) or by activating adenylate cyclase (NaF) reduced or eliminated
      sclerotial development in S. sclerotiorum. Growth in the presence of 5 mM
      caffeine correlated with increased levels of endogenous cAMP in mycelia. In
      addition, incorporation of cAMP into the growth medium decreased or eliminated
      the production of sclerotia in a concentration-dependent manner and increased the
      accumulation of oxalic acid. Inhibition of sclerotial development was cAMP
      specific, as exogenous cyclic GMP, AMP, and ATP did not influence sclerotial
      development. Transfer of developing cultures to cAMP-containing medium at
      successive time points demonstrated that cAMP inhibits development prior to or
      during sclerotial initiation. Together, these results indicate that cAMP plays a
      role in the early transition between mycelial growth and sclerotial development.

PMID- 9647828
TI  - A highly selective PCR protocol for detecting 16S rRNA genes of the genus
      Pseudomonas (sensu stricto) in environmental samples.
AB  - Pseudomonas species are plant, animal, and human pathogens; exhibit plant
      pathogen-suppressing properties useful in biological control; or express
      metabolic versatilities valued in biotechnology and bioremediation. Specific
      detection of Pseudomonas species in the environment may help us gain a more
      complete understanding of the ecological significance of these microorganisms.
      The objective of this study was to develop a PCR protocol for selective detection
      of Pseudomonas (sensu stricto) in environmental samples. Extensive database
      searches identified a highly selective PCR primer pair for amplification of
      Pseudomonas 16S rRNA genes. A protocol that included PCR amplification and
      restriction analysis, a general cloning and sequencing strategy, and phylogenetic
      analyses was developed. The PCR protocol was validated by testing 50 target and
      14 nontarget pure cultures, which confirmed the selectivity to 100%. Further
      validation used amplification of target sequences from purified bulk soil DNA
      followed by cloning of PCR products. Restriction analysis with HaeIII revealed
      eight different fragmentation patterns among 36 clones. Sequencing and
      phylogenetic analysis of 8 representative clones indicated that 91.7% of the
      products were derived from target organisms of the PCR protocol. Three patterns,
      representing only 8.3% of the 36 clones, were derived from non-Pseudomonas or
      chimeric PCR artifacts. Three patterns, representing 61.1% of the clones,
      clustered with sequences of confirmed Pseudomonas species, whereas two patterns,
      representing 30.6% of the clones, formed a novel phylogenetic cluster closely
      associated with Pseudomonas species. The results indicated that the Pseudomonas
      selective PCR primers were highly specific and may represent a powerful tool for
      Pseudomonas population structure analyses and taxonomic confirmations.

PMID- 9647829
TI  - Use of green fluorescent protein to tag and investigate gene expression in marine
      bacteria.
AB  - Two broad-host-range vectors previously constructed for use in soil bacteria (A.
      G. Matthysse, S. Stretton, C. Dandie, N. C. McClure, and A. E. Goodman, FEMS
      Microbiol. Lett. 145:87-94, 1996) were assessed by epifluorescence microscopy for
      use in tagging three marine bacterial species. Expression of gfp could be
      visualized in Vibrio sp. strain S141 cells at uniform levels of intensity from
      either the lac or the npt-2 promoter, whereas expression of gfp could be
      visualized in Psychrobacter sp. strain SW5H cells at various levels of intensity
      only from the npt-2 promoter. Green fluorescent protein (GFP) fluorescence was
      not detected in the third species, Pseudoalteromonas sp. strain S91, when the gfp
      gene was expressed from either promoter. A new mini-Tn10-kan-gfp transposon was
      constructed to investigate further the possibilities of fluorescence tagging of
      marine bacteria. Insertion of mini-Tn10-kan-gfp generated random stable mutants
      at high frequencies with all three marine species. With this transposon, strongly
      and weakly expressed S91 promoters were isolated. Visualization of GFP by
      epifluorescence microscopy was markedly reduced when S91 (mini-Tn10-kan-gfp)
      cells were grown in rich medium compared to that when cells were grown in minimal
      medium. Mini-Tn10-kan-gfp was used to create an S91 chitinase-negative, GFP
      positive mutant. Expression of the chi-gfp fusion was induced in cells exposed to
      N'-acetylglucosamine or attached to chitin particles. By laser scanning confocal
      microscopy, biofilms consisting of microcolonies of chi-negative, GFP+ S91 cells
      were found to be localized several microns from a natural chitin substratum.
      Tagging bacterial strains with GFP enables visualization of, as well as
      monitoring of gene expression in, living single cells in situ and in real time.

PMID- 9647830
TI  - Spatial and temporal variation of phenanthrene-degrading bacteria in intertidal
      sediments.
AB  - Phenanthrene-degrading bacteria were isolated from a 1-m2 intertidal sediment
      site in Boston Harbor. Samples were taken six times over 2 years. A total of 432
      bacteria were isolated and characterized by biochemical testing. When clustered
      on the basis of phenotypic characteristics, the isolates could be separated into
      68 groups at a similarity level of approximately 70%. Several groups (a total of
      200 isolates) corresponded to well-characterized species belonging the genera
      Vibrio and Pseudomonas. Only 51 of the 437 isolates (< 11.7% of the total)
      hybridized to a DNA probe that encodes the upper pathway of naphthalene and
      phenanthrene degradation in Pseudomonas putida NCIB 9816. A cluster analysis
      indicated that the species composition of the phenanthrene-degrading community
      changed significantly from sampling date to sampling date. At one sampling time,
      12 6-mm-diameter core subsamples were taken within the 1-m2 site to determine the
      spatial variability of the degrading communities. An analysis of molecular
      variance, performed with the phenotypic characteristics, indicated that only 6%
      of the variation occurred among the 12 subsamples, suggesting that the subsamples
      were almost identical in composition. We concluded that the communities of
      phenanthrene-degrading bacteria in the sediments are very diverse, that the
      community structure undergoes significant change with time but does not vary
      significantly on a spatial scale of centimeters, and that the predominant genes
      that encode phenanthrene degradation in the communities are not well
      characterized.

PMID- 9647831
TI  - Aerobic mineralization of 2,6-dichlorophenol by Ralstonia sp. strain RK1.
AB  - A new aerobic bacterium was isolated from the sediment of a freshwater pond close
      to a contaminated site at Amponville (France). It was enriched in a fixed-bed
      reactor fed with 2,6-dichlorophenol (2,6-DCP)as the sole carbon and energy source
      at pH 7.5 and room temperature. The degradation of 2,6-DCP followed Monod
      kinetics at low initial concentrations. At concentrations above 300 microM (50
      mg.liter-1), 2,6-DCP increasingly inhibited its own degradation. The base
      sequence of the 16S ribosomal DNA allowed us to assign the bacterium to the genus
      Ralstonia (formerly Alcaligenes). The substrate spectrum of the bacterium
      includes toluene, benzene, chlorobenzene, phenol, and all four ortho- and para
      substituted mono- and dichlorophenol isomers. Substituents other than chlorine
      prevented degradation. The capacity to degrade 2,6-DCP was examined in two fixed
      bed reactors. The microbial population grew on and completely mineralized 2,6-DCP
      at 2,6-DCP concentrations up to 740 microM in continuous reactor culture supplied
      with H2O2 as an oxygen source. Lack of peroxide completely stopped further
      degradation of 2,6-DCP. Lowering the acid-neutralizing capacity of the medium to
      1/10th the original capacity led to a decrease in the pH of the effluent from 7
      to 6 and to a significant reduction in the degradation activity. A second fixed
      bed reactor successfully removed low chlorophenol concentrations (20 to 26
      microM) with hydraulic residence times of 8 to 30 min.

PMID- 9647832
TI  - Capillary Electrophoresis Measurements of Electrophoretic Mobility for Colloidal
      Particles of Biological Interest.
AB  - The electrophoretic mobilities of three bacterial strains were investigated by
      capillary electrophoresis (CE) and were compared with results obtained by
      microelectrophoresis (ME). The CE measurements yielded bimodal electropherograms
      for two of the strains, thus illustrating for the first time that surface charge
      variations within a monoclonal population can be probed by CE. Intrapopulation
      variations were not detected by ME. The mobilities of three chemically distinct
      types of latex microspheres were also measured. Differences between the mean
      mobilities obtained by CE and ME were not statistically significant (P </= 0.50);
      the standard deviations of the CE measurements were typically 2 to 10 times
      smaller than those obtained by comparable ME measurements. The reproducibility of
      CE permitted batch-to-batch mobility variations to be probed for the bacteria
      (one of the strains exhibited such variations), and aggregation was evident in
      one of the latex suspensions. These effects were not measurable with ME.

PMID- 9647833
TI  - Biodegradation of variable-chain-length alkanes at low temperatures by a
      psychrotrophic Rhodococcus sp.
AB  - The psychorotrophic Rhodococcus sp. strain Q15 was examined for its ability to
      degrade individual n-alkanes and diesel fuel at low temperatures, and its alkane
      catabolic pathway was investigated by biochemical and genetic techniques. At 0
      and 5 degrees C, Q15 mineralized the short-chain alkanes dodecane and hexadecane
      to a greater extent than that observed for the long-chain alkanes octacosane and
      dotriacontane. Q15 utilized a broad range of aliphatics (C10 to C21 alkanes,
      branched alkanes, and a substituted cyclohexane) present in diesel fuel at 5
      degrees C. Mineralization of hexadecane at 5 degrees C was significantly greater
      in both hydrocarbon-contaminated and pristine soil microcosms seeded with Q15
      cells than in uninoculated control soil microcosms. The detection of hexadecane
      and dodecane metabolic intermediates (1-hexadecanol and 2-hexadecanol and 1
      dodecanol and 2-dodecanone, respectively) by solid-phase microextraction-gas
      chromatography-mass spectrometry and the utilization of potential metabolic
      intermediates indicated that Q15 oxidizes alkanes by both the terminal oxidation
      pathway and the subterminal oxidation pathway. Genetic characterization by PCR
      and nucleotide sequence analysis indicated that Q15 possesses an aliphatic
      aldehyde dehydrogenase gene highly homologous to the Rhodococcus erythropolis the
      A gene. Rhodococcus sp. strain Q15 possessed two large plasmids of approximately
      90 and 115 kb (shown to mediate Cd resistance) which were not required for alkane
      mineralization, although the 90-kb plasmid enhanced mineralization of some
      alkanes and growth on diesel oil at both 5 and 25 degrees C.

PMID- 9647834
TI  - Seasonal and spatial variability of bacterial and archaeal assemblages in the
      coastal waters near Anvers Island, Antarctica.
AB  - A previous report of high levels of members of the domain Archaeal in Antarctic
      coastal waters prompted us to investigate the ecology of Antarctic planktonic
      prokaryotes. rRNA hybridization techniques and denaturing gradient gel
      electrophoresis (DGGE) analysis of the bacterial V3 region were used to study
      variation in Antarctic picoplankton assemblages. In Anvers Island nearshore
      waters during late winter to early spring, the amounts of archaeal rRNA ranged
      from 17.1 to 3.6% of the total picoplankton rRNA in 1996 and from 16.0 to 1.0% of
      the total rRNA in 1995. Offshore in the Palmer Basin, the levels of archaeal rRNA
      throughout the water column were higher (average, 24% of the total rRNA) during
      the same period in 1996. The archaeal rRNA levels in nearshore waters followed a
      highly seasonal pattern and markedly decreased during the austral summer at two
      stations. There was a significant negative correlation between archaeal rRNA
      levels and phytoplankton levels (as inferred from chlorophyll a concentrations)
      in nearshore surface waters during the early spring of 1995 and during an 8-month
      period in 1996 and 1997. In situ hybridization experiments revealed that 5 to 14%
      of DAPI (4',6-diamidino-2-phenylindole)-stained cells were archaeal,
      corresponding to 0.9 x 10(4) to 2.7 x 10(4) archaeal cells per ml, in late winter
      1996 samples. Analysis of bacterial ribosomal DNA fragments by DGGE revealed that
      the assemblage composition may reflect changes in water column stability, depth,
      or season. The data indicate that changes in Antarctic seasons are accompanied by
      significant shifts in the species composition of bacterioplankton assemblages and
      by large decrease in the relative proportion of archaeal rRNA in the nearshore
      water column.

PMID- 9647835
TI  - Distribution of Clostridium perfringens and fecal sterols in a benthic coastal
      marine environment influenced by the sewage outfall from McMurdo Station,
      Antarctica.
AB  - The spatial distribution, movement, and impact of the untreated wastewater
      outfall from McMurdo Station, Antarctica, were investigated under early austral
      summer conditions. The benthic environment was examined to determine the
      distribution of Clostridium perfringens in sediment cores and the intestinal
      contents of native invertebrates and fish along a transect of stations. These
      stations extended ca. 411 m south of the outfall. The findings revealed that the
      concentration of C. perfringens decreased with depth in the sediment and distance
      from the outfall. High percentages of tunicates and sea urchins were colonized
      with this bacterium along the transect. Coprostanol concentrations were also
      measured in sediment samples taken from each of the transect stations, and a
      similar trend was observed. These results are in agreement with the findings of
      previous studies performed with the water column and collectively provide
      evidence that the disposal of domestic wastes deserves special consideration in
      polar marine environments.

PMID- 9647836
TI  - phnE and glpT genes enhance utilization of organophosphates in Escherichia coli K
      12.
AB  - Wild-type Escherichia coli K-12 strain JA221 grows poorly on low concentrations
      (< or = 1 mM) of diisopropyl fluorophosphate and its hydrolysis product,
      diisopropyl phosphate (DIPP), as sole phosphorus sources. Spontaneous
      organophosphate utilization (OPU) mutants were isolated that efficiently utilized
      these alternate sources of phosphate. A genomic library was constructed from one
      such OPU mutant, and two genes were isolated that conferred the OPU phenotype to
      strain JA221 upon transformation. These genes were identified as phnE and glpT.
      The original OPU mutation represented phnE gene activation and corresponded to
      the same 8-bp unit deletion from the cryptic wild-type E. coli K-12 phnE gene
      that has been shown previously to result in phnE activation. In comparison,
      sequence analysis revealed that the observed OPU phenotype conferred by the glpT
      gene was not the result of a mutation. PCR clones of glpT from both the mutant
      and the wild type were found to confer the OPU phenotype to JA221 when they were
      present on the high-copy-number pUC19 plasmid but not when they were present on
      the low-copy-number pWSK29 plasmid. This suggests that the OPU phenotype
      associated with the glpT gene is the result of amplification and overproduction
      of the glpT gene product. Both the active phnE and multicopy glpT genes
      facilitated effective metabolism of low concentrations of DIPP, whereas only the
      active phnE gene could confer the ability to break down a chromogenic substrate,
      5-bromo-4-chloro-3-indoxyl phosphate-p-toluidine (X-Pi). This result indicates
      that in E. coli, X-Pi is transported exclusively by the Phn system, whereas DIPP
      (or its metabolite) may be transported by both Phn and Glp systems.

PMID- 9647838
TI  - Modeling of Growth of Lactobacillus sanfranciscensis and Candida milleri in
      Response to Process Parameters of Sourdough Fermentation.
AB  - We investigated the effect of the ecological factors pH, temperature, ionic
      strength, and lactate, acetate, and ethanol levels on Candida milleri and two
      strains of Lactobacillus sanfranciscensis, organisms representative of the
      microflora of sourdough. A mathematical model describing the single and combined
      effects of these factors on the growth of these organisms was established in
      accordance with the following criteria: quality of fit, biological significance
      of the parameters, and applicability of the in vitro data to in situ processes.
      The growth rates of L. sanfranciscensis LTH1729 and LTH2581 were virtually
      identical under all conditions tested. These organisms tolerated >160 mmol of
      undissociated acetic acid per liter. Growth occurred in the pH range of 3.9 to
      6.7 and was completely inhibited by 4% NaCl. C. milleri had a lower optimum
      temperature for growth (27 degreesC) than the lactobacilli. The growth of the
      yeast was not affected by pH in the range of 3.5 to 7, and up to 8% NaCl was
      tolerated. Complete inhibition of growth occurred at 150 mmol of undissociated
      acetic acid per liter, but acetate at concentrations of up to 250 mmol/liter
      exerted virtually no effect. The model provides insight into factors contributing
      to the stability of the sourdough microflora and can facilitate the design of
      novel sourdough processes.

PMID- 9647837
TI  - Cloning and expression of the inositol monophosphatase gene from Methanococcus
      jannaschii and characterization of the enzyme.
AB  - Inositol monophosphatase (EC 3.1.3.25) plays a pivotal role in the biosynthesis
      of di-myo-inositol-1,1'-phosphate, an osmolyte found in hyperthermophilic
      archaeal. Given the sequence homology between the MJ109 gene product of
      Methanococcus jannaschii and human inositol monophosphatase, the MJ109 gene was
      cloned and expressed in Escherichia coli and examined for inositol
      monophosphatase activity. The purified MJ109 gene product showed inositol
      monophosphatase activity with kinetic parameters (K(m) = 0.091 +/- 0.016 mM; Vmax
      = 9.3 +/- 0.45 mumol of Pi min-1 mg of protein-1) comparable to those of
      mammalian and E. coli enzymes. Its substrate specificity, Mg2+ requirement, Li+
      inhibition, subunit association (dimerization), and heat stability were studied
      and compared to those of other inositol monophosphatases. The lack of inhibition
      by low concentrations of Li+ and high concentrations of Mg2+ and the high rates
      of hydrolysis of glucose-1-phosphate and p-nitrophenylphosphate are the most
      pronounced differences between the archaeal inositol monophosphatase and those
      from other sources. The possible causes of these kinetic differences are
      discussed, based on the active site sequence alignment between M. jannaschii and
      human inositol monophosphatase and the crystal structure of the mammalian enzyme.

PMID- 9647839
TI  - Cloning of Phanerochaete chrysosporium leu2 by complementation of bacterial
      auxotrophs and transformation of fungal auxotrophs.
AB  - A Phanerochaete chrysosporium cDNA library was constructed in an expression
      vector that allows expression in both Escherichia coli and Saccharomyces
      cerevisiae. This expression vector, lambda YES, contains the lacZ promoter for
      expression in E. coli and the GAL1 promoter for expression in yeast. A number of
      genes were cloned by complementation of bacterial amino acid auxotrophs. The cDNA
      encoding the beta-isopropylmalate dehydrogenase from P. chrysosporium was
      characterized further. The genomic clone (gleu2) was subsequently isolated and
      was used successfully as a selectable marker to transform P. chrysosporium
      auxotrophs for LEU2. Protoplasts for transformation were prepared with readily
      obtained conidiospores rather than with basidiospores, which were used in
      previous P. chrysosporium transformation procedures. The method described here
      allows other genes to be isolated from P. chrysosporium for use as selectable
      markers.

PMID- 9647840
TI  - Trifolitoxin Production Increases Nodulation Competitiveness of Rhizobium etli
      CE3 under Agricultural Conditions.
AB  - A major barrier to the use of nitrogen-fixing inoculum strains for the
      enhancement of legume productivity is the inability of commercially available
      strains to compete with indigenous rhizobia for nodule formation. Despite
      extensive research on nodulation competitiveness, there are no examples of field
      efficacy studies of strains that have been genetically improved for nodulation
      competitiveness. We have shown previously that production of the peptide
      antibiotic trifolitoxin (TFX) by Rhizobium etli results in significantly
      increased nodule occupancy values in nonsterile soil in growth chamber
      experiments (E. A. Robleto, A. J. Scupham, and E. W. Triplett, Mol. Plant-Microbe
      Interact. 10:228-233, 1997). To determine whether TFX production by Rhizobium
      etli increases nodulation competitiveness in field-grown plants, seeds of
      Phaseolus vulgaris were inoculated with mixtures of Rhizobium etli strains at
      different ratios. The three nearly isogenic inoculum strains used included TFX
      producing and non-TFX-producing strains, as well as a TFX-sensitive reference
      strain. Data was obtained over 2 years for nodule occupancy and over 3 years for
      assessment of the effect of the TFX production phenotype on grain yield. In
      comparable mixtures in which the test strain accounted for between 5 and 50% of
      the inoculum, the TFX-producing strain exhibited at least 20% greater nodule
      occupancy than the non-TFX-producing strain in both years. The TFX production
      phenotype had no effect on grain yield over 3 years; the average yields reached
      2,400 kg/ha. These results show that addition of the TFX production phenotype
      significantly increases nodule occupancy under field conditions without adverse
      effects on grain yield. As we used common inoculation methods in this work, there
      are no practical barriers to the commercial adoption of the TFX system for
      agriculture.

PMID- 9647841
TI  - Effect of Insertion Site and Metabolic Load on the Environmental Fitness of a
      Genetically Modified Pseudomonas fluorescens Isolate.
AB  - An isolate of Pseudomonas fluorescens (SBW25) was modified with different marker
      genes (lacZY, aph-1, and xylE). These marker genes were inserted singly or in
      combination into two separate (1 Mbp apart) and presumably nonessential sites (-6
      and Ee) on the chromosome of SBW25. This allowed the production of a range of
      genetically modified SBW25 variants that differed with respect to insertion site
      of the marker genes and metabolic burden. The environmental fitness of the
      different SBW25 variants was tested in soil, in the rhizosphere of wheat and pea,
      and on the phylloplane of wheat. Reduced environmental fitness of the different
      variants was mainly attributed to the extra metabolic burden of novel gene
      expression, whereas choice of insertion site was of little significance. Changes
      in environmental fitness were dependent on the environmental conditions; an
      environment, such as soil, with a low microbial carrying capacity had a negative
      effect on the environmental fitness of variants with a large metabolic load. In
      environments with a larger carrying capacity, such as the rhizosphere of pea,
      environmental fitness of variants with a large metabolic load was not
      significantly different from that of variants with a smaller metabolic burden.

PMID- 9647842
TI  - Quantification of toxic cyanobacteria in water by use of competitive PCR followed
      by sequence-specific labeling of oligonucleotide probes.
AB  - A complete nucleic-acid-based assay which consists of sample preparation, DNA
      amplification, and chromogenic detection was developed for quantifying potential
      toxin-producing cyanobacteria of interest to the public. The sample preparation
      strategy involves the same solid phase for cell concentration and DNA
      purification. For the detection step, we used a combination of competitive PCR
      amplification, sequence-specific labeling of oligonucleotide probes,
      hybridization of the labeled oligonucleotides to immobilized complements and,
      finally, chromogenic detection. The complete assay was tested with water
      containing toxin-producing cyanobacteria belonging to the genus Microcystis. A
      detection limit of 100 cells/ml and a quantitative range of more than 3 orders of
      magnitude were obtained. This approach can easily be adapted to a wide range of
      bacterial species and has the potential for simultaneous detection and
      quantitation of several different target organisms by a single assay.

PMID- 9647843
TI  - Development of a lipase fermentation process that uses a recombinant Pseudomonas
      alcaligenes strain.
AB  - Pseudomonas alcaligenes M-1 secretes an alkaline lipase, which has excellent
      characteristics for the removal of fatty stains under modern washing conditions.
      A fed-batch fermentation process based on the secretion of the alkaline lipase
      from P. alcaligenes was developed. Due to the inability of P. alcaligenes to grow
      on glucose, citric acid and soybean oil were applied as substrates in the batch
      phase and feed phase, respectively. The gene encoding the high-alkaline lipase
      from P. alcaligenes was isolated and characterized. Amplification of lipase gene
      copies in P. alcaligenes with the aid of low- and high-copy-number plasmids
      resulted in an increase of lipase expression that was apparently colinear with
      the gene copy number. It was found that overexpression of the lipase helper gene,
      lipB, produced a stimulating effect in strains with high copy numbers (> 20) of
      the lipase structural gene, lipA. In strains with lipA on a low-copy-number
      vector, the lipB gene did not show any effect, suggesting that LipB is required
      in a low ratio to LipA only. During scaling up of the fermentation process to 100
      m3, severe losses in lipase productivity were observed. Simulations have
      identified an increased level of dissolved carbon dioxide as the most probable
      cause for the scale-up losses. A large-scale fermentation protocol with a reduced
      dissolved carbon dioxide concentration resulted in a substantial elimination of
      the scale-up loss.

PMID- 9647844
TI  - Intergeneric transfer of conjugative and mobilizable plasmids harbored by
      Escherichia coli in the gut of the soil microarthropod Folsomia candida
      (Collembola).
AB  - The gut of the soil microarthropod Folsomia candida provides a habitat for a high
      density of bacterial cells (T. Thimm, A. Hoffmann, H. Borkott, J. C. Munch, and
      C. C. Tebbe, Appl. Environ. Microbiol. 64:2660-2669, 1998). We investigated
      whether these gut bacteria act as recipients for plasmids from Escherichia coli.
      Filter mating with E. coli donor cells and collected feces of F. candida revealed
      that the broad-host-range conjugative plasmid pRP4-luc (pRP4 with a luciferase
      marker gene) transferred to fecal bacteria at estimated frequencies of 5.4 x 10(
      1) transconjugants per donor. The mobilizable plasmid pSUP104-luc was transferred
      from the IncQ mobilizing strain E. coli S17-1 and less efficiently from the IncF1
      mobilizing strain NM522 but not from the nonmobilizing strain HB101. When S17-1
      donor strains were fed to F. candida, transconjugants of pRP4-luc and pSUP104-luc
      were isolated from feces. Additionally, the narrow-host-range plasmid pSUP202-luc
      was transferred to indigenous bacteria, which, however, could not maintain this
      plasmid. Inhibition experiments with nalidixic acid indicated that pRP4-luc
      plasmid transfer took place in the gut rather than in the feces. A remarkable
      diversity of transconjugants was isolated in this study: from a total of 264
      transconjugants, 15 strains belonging to the alpha, beta, or gamma subclass of
      the class Proteobacteria were identified by DNA sequencing of the PCR-amplified
      16S rRNA genes and substrate utilization assays (Biolog). Except for Alcaligenes
      faecalis, which was identified by the Biolog assay, none of the isolates was
      identical to reference strains from data banks. This study indicates the
      importance of the microarthropod gut for enhanced conjugative gene transfer in
      soil microbial communities.

PMID- 9647845
TI  - The gut of the soil microarthropod Folsomia candida (Collembola) is a frequently
      changeable but selective habitat and a vector for microorganisms.
AB  - Interaction potentials between soil microarthropods and microorganisms were
      investigated with Folsomia candida (Insecta, Collembola) in microcosm laboratory
      experiments. Microscopic analysis revealed that the volumes of the simple, rod
      shaped guts of adult specimens varied with their feeding activity, from 0.7 to
      11.2 nl. A dense layer of bacterial cells, associated with the peritrophic
      membrane, was detected in the midgut by scanning electron microscopy. Depending
      on the molting stage, which occurred at intervals of approximately 4 days,
      numbers of heterotrophic, aerobic gut bacteria changed from 4.9 x 10(2) to 2.3 x
      10(6) CFU per specimen. A total of 11 different taxonomic bacterial groups and
      the filamentous fungus Acremonium charticola were isolated from the guts of five
      F. candida specimens. The most abundant isolate was related to Erwinia amylovora
      (96.2% DNA sequence similarity to its 16S rRNA gene). F. candida preferred to
      feed on Pseudomonas putida and three indigenous gut isolates rather than eight
      different type culture strains. When luciferase reporter gene-tagged bacterial
      strains were pulse fed to F. candida, gut isolates were continuously shed for 8
      days to several weeks but Escherichia coli HB101 was shed for only 1 day. Ratios
      of ingested to released bacterial cells demonstrated that populations of
      nonindigenous gut bacteria like Sinorhizobium meliloti L33 and E. coli HB101 were
      reduced by more than 4 orders of magnitude but that the population of gut isolate
      Alcaligenes faecalis HR4 was reduced only 500-fold. This work demonstrates that
      F. candida represents a frequently changeable but selective habitat for bacteria
      in terrestrial environments and that microarthropods have to be considered
      factors that modify soil microbial communities.

PMID- 9647846
TI  - In Situ Detection of High Levels of Horizontal Plasmid Transfer in Marine
      Bacterial Communities.
AB  - Gene transfer of the conjugative plasmid pBF1 from Pseudomonas putida to
      indigenous bacteria in seawater was investigated with a detection system for gene
      transfer based on the green fluorescent protein (GFP) (C. Dahlberg et al., Mol.
      Biol. Evol. 15:385-390, 1998). pBF1 was tagged with the gfp gene controlled by a
      lac promoter which is down regulated in the donor cell by a chromosomal repressor
      (lacIq). The plasmid donor cells (Pseudomonas putida KT2442) subsequently do not
      express gfp. Transfer to recipient strains lacking the repressor results in
      expression of gfp. The transconjugant can subsequently be detected by
      epifluorescence microscopy on a single-cell level. By using this method, transfer
      of pBF1::gfp and expression of the gfp gene were first shown to occur during
      nutrient-limiting conditions to several defined recipient bacteria in artificial
      seawater. Second, we measured transfer of pBF1 from P. putida to the marine
      bacterial community directly in seawater samples, on a single-cell level, without
      limiting the detection of gene transfer to the culturable fraction of bacteria.
      Plasmid transfer was detected on surfaces and in bulk seawater. Seawater bacteria
      with different morphologies were shown to receive the plasmid. Gene transfer
      frequencies of 2.3 x 10(-6) to 2.2 x 10(-4) transconjugants per recipient were
      recorded after 3 days of incubation.

PMID- 9647848
TI  - A fluorescent Gram stain for flow cytometry and epifluorescence microscopy.
AB  - The fluorescent nucleic acid binding dyes hexidium iodide (HI) and SYTO 13 were
      used in combination as a Gram stain for unfixed organisms in suspension. HI
      penetrated gram-positive but not gram-negative organisms, whereas SYTO 13
      penetrated both. When the dyes were used together, gram-negative organisms were
      rendered green fluorescent by SYTO 13; conversely, gram-positive organisms were
      rendered red-orange fluorescent by HI, which simultaneously quenched SYTO 13
      green fluorescence. The technique correctly predicted the Gram status of 45
      strains of clinically relevant organisms, including several known to be gram
      variable. In addition, representative strains of gram-positive anaerobic
      organisms, normally decolorized during the traditional Gram stain procedure, were
      classified correctly by this method.

PMID- 9647847
TI  - Increased carotenoid production by the food yeast Candida utilis through
      metabolic engineering of the isoprenoid pathway.
AB  - The yeast Candida utilis does not possess an endogenous biochemical pathway for
      the synthesis of carotenoids. The central isoprenoid pathway concerned with the
      synthesis of prenyl lipids is present in C. utilis and active in the biosynthesis
      of ergosterol. In our previous study, we showed that the introduction of
      exogenous carotenoid genes, crtE, crtB, and crtI, responsible for the formation
      of lycopene from the precursor farnesyl pyrophosphate, results in the C. utilis
      strain that yields lycopene at 1.1 mg per g (dry weight) of cells (Y. Miura, K.
      Kondo, T. Saito, H. Shimada, P. D. Fraser, and N. Misawa, Appl. Environ.
      Microbiol. 64:1226-1229, 1998). Through metabolic engineering of the isoprenoid
      pathway, a sevenfold increase in the yield of lycopene has been achieved. The
      influential steps in the pathway that were manipulated were 3-hydroxy
      methylglutaryl coenzyme A (HMG-CoA) reductase, encoded by the HMG gene, and
      squalene synthase, encoded by the ERG9 gene. Strains overexpressing the C. utilis
      HMG-CoA reductase yielded lycopene at 2.1 mg/g (dry weight) of cells. Expression
      of the HMG-CoA catalytic domain alone gave 4.3 mg/g (dry weight) of cells;
      disruption of the ERG9 gene had no significant effect, but a combination of ERG9
      gene disruption and the overexpression of the HMG catalytic domain yielded
      lycopene at 7.8 mg/g (dry weight) of cells. The findings of this study illustrate
      how modifications in related biochemical pathways can be utilized to enhance the
      production of commercially desirable compounds such as carotenoids.

PMID- 9647849
TI  - Specific detection of Legionella pneumophila: construction of a new 16S rRNA
      targeted oligonucleotide probe.
AB  - Based on comparative sequence analysis, we have designed an oligonucleotide probe
      complementary to a region of 16S rRNA of Legionella pneumophila which allows the
      differentiation of L. pneumophila from other Legionella species without
      cultivation. The specificity of the new probe, LEGPNE1, was tested by in situ
      hybridization to a total of four serogroups of six strains of L. pneumophila,
      five different Legionella spp. and three nonlegionella species as reference
      strains. Furthermore, L. pneumophila cells could be easily distinguished from
      Legionella micdadei and Pseudomonas aeruginosa cells by using in situ
      hybridization with probes LEGPNE1, LEG705, and EUB338 after infection of the
      protozoan Acanthamoeba castellanii.

PMID- 9647850
TI  - Microbial Community Composition of Wadden Sea Sediments as Revealed by
      Fluorescence In Situ Hybridization.
AB  - The microbial community composition of Wadden Sea sediments of the German North
      Sea coast was investigated by in situ hybridization with group-specific
      fluorescently labeled, rRNA-targeted oligonucleotides. A large fraction (up to
      73%) of the DAPI (4',6-diamidino-2-phenylindole)-stained cells hybridized with
      the bacterial probes. Nearly 45% of the total cells could be further identified
      as belonging to known phyla. Members of the Cytophaga-Flavobacterium cluster were
      most abundant in all layers, followed by the sulfate-reducing bacteria.

PMID- 9647851
TI  - Effectiveness of SYTOX Green stain for bacterial viability assessment.
AB  - The effectiveness of SYTOX Green nucleic acid stain for measuring bacterial
      viability was tested on starved populations of Escherichia coli and Salmonella
      typhimurium. This stain underestimates the fraction of dead cells within starved
      populations containing cells with damaged nucleic acids or membranes. Its
      application to natural samples should be considered with caution.

PMID- 9647852
TI  - Enhanced broth media for selective growth of Vibrio vulnificus.
AB  - Rapid detection of Vibrio vulnificus can be enhanced by optimizing the components
      of enrichment broth. PNC (5% peptone, 1% NaCl, and 0.08% cellobiose [pH 8.0])
      enhanced the growth of V. vulnificus compared to alkaline peptone broth. PNCC
      (PNC with 1.0 to 4.1 U of colistin methanesulfonate per ml) increased the growth
      of low levels of V. vulnificus while suppressing non-target bacteria.

PMID- 9647853
TI  - Lyme disease Borrelia species in northeastern China resemble those isolated from
      far eastern Russia and Japan.
AB  - Fifty-nine Borrelia burgdorferi sensu lato culture isolates collected from
      northeastern China were characterized by 5S-23S rRNA intergenic spacer
      restriction fragment length polymorphism (RFLP) analysis and reactivity with
      monoclonal antibodies (MAbs). Among 59 culture isolates, 30 (50.8%) were Borrelia
      garinii and 17 (28.8%) were Borrelia afzelii, 2 were mixtures composed of B.
      garinii with RFLP pattern B and B. garinii with pattern C, and 9 were mixtures
      composed of B. garinii and B. afzelii. One isolate, ChY13p, produced a unique
      pattern and was identified as B. garinii based on analyses of 16S rRNA gene
      sequence, flagellin PCR-RFLP typing, and MAb reactivities. No Borrelia
      burgdorferi sensu stricto or Borrelia japonica isolates were detected. The
      results indicate that Lyme disease Borrelia species in northeastern China
      resemble those of Borrelia isolates from far eastern Russia and Japan.

PMID- 9647855
TI  - Design and Application of Two Rapid Screening Techniques for Isolation of Mn(IV)
      Reduction-Deficient Mutants of Shewanella putrefaciens.
AB  - Chemical mutagenesis procedures and two newly developed rapid plate assays were
      used to identify two Mn(IV) reduction-deficient (Mnr) mutants of Shewanella
      putrefaciens. All eleven members of a set of previously isolated Fe(III)
      reduction-deficient (Fer) mutants displayed Mnr-positive phenotypes on the plate
      assays and were also capable of anaerobic growth on Mn(IV) as the sole terminal
      electron acceptor.

PMID- 9647854
TI  - Plasposons: modular self-cloning minitransposon derivatives for rapid genetic
      analysis of gram-negative bacterial genomes.
AB  - A series of modular mini-transposon derivatives which permit the rapid cloning
      and mapping of the DNA flanking the minitransposon's site of insertion has been
      developed. The basic plasposon, named TnMod, consists of the Tn5 inverted
      repeats, a conditional origin of replication, rare restriction endonuclease
      multiple cloning sites, and exchangeable antibiotic resistance cassettes. The
      broad host range and low target DNA sequence specificity of the Tn5 transposase,
      in combination with the flexibility afforded by the modular arrangement of TnMod,
      result in a versatile tool for the mapping of insertional mutations and the rapid
      recovery of clones from gram-negative bacteria.

PMID- 9647856
TI  - Use of luciferase genes as biosensors to study bacterial physiology in the
      digestive tract.
AB  - A method based on the use of the bacterial luciferase genes was developed in
      order to investigate Lactococcus lactis gene expression in the mouse digestive
      tract. Germfree mice were monoassociated with different strains containing
      transcriptional fusions of promoters with the luciferase genes. Our results
      demonstrate that this method is readily applicable to the study of promoter
      strength and physiology of bacteria in the digestive tract.

PMID- 9647857
TI  - Insecticidal activity of Bacillus laterosporus.
AB  - The Bacillus laterosporus strains 921 and 615 were shown to have toxicity for
      larvae of the mosquitoes Aedes aegypti, Anopheles stephensi, and Culex pipiens.
      The larvicidal activity of B. laterosporus was associated with spores and
      crystalline inclusions. Purified B. laterosporus 615 crystals were highly toxic
      for Aedes aegypti and Anopheles stephensi.

PMID- 9647858
TI  - Phanerochaete flavido-alba Laccase Induction and Modification of Manganese
      Peroxidase Isoenzyme Pattern in Decolorized Olive Oil Mill Wastewaters.
AB  - Lignin-degrading enzymes were partially purified from supernatant solutions
      obtained from Phanerochaete flavido-alba-decolorized olive oil mill wastewaters
      (OMW). The dominant enzymes, manganese peroxidases, exhibited different isoform
      patterns in decolorized OMW-containing cultures than in residue-free samples.
      Laccase induction was also detected in OMW-containing cultures but not in control
      cultures.

PMID- 9647859
TI  - A chromosomally based tod-luxCDABE whole-cell reporter for benzene, toluene,
      ethybenzene, and xylene (BTEX) sensing.
AB  - A tod-luxCDABE fusion was constructed and introduced into the chromosome of
      Pseudomonas putida F1, yielding the strain TVA8. This strain was used to examine
      the induction of the tod operon when exposed to benzene, toluene, ethylbenzene,
      and xylene (BTEX) compounds and aqueous solutions of JP-4 jet fuel constituents.
      Since this system contained the complete lux cassette (luxCDABE), bacterial
      bioluminescence in response to putative chemical inducers of the tod operon was
      measured on-line in whole cells without added aldehyde substrate. There was an
      increasing response to toluene concentrations from 30 micrograms/liter to 50
      mg/liter, which began to saturate at higher concentrations. The detection limit
      was 30 micrograms/liter. There was a significant light response to benzene, m-
      and p-xylenes, phenol, and water-soluble JP-4 jet fuel components, but there was
      no bioluminescence response upon exposure to o-xylene. The transposon insertion
      was stable and had no negative effect on cell growth.

PMID- 9647860
TI  - Giardia sp. cysts and infectious Cryptosporidium parvum oocysts in the feces of
      migratory Canada geese (Branta canadensis).
AB  - Fecal droppings of migratory Canada geese, Branta canadensis, collected from nine
      sites near the Chesapeake Bay (Maryland), were examined for the presence of
      Cryptosporidium parvum and Giardia spp. Cryptosporidium sp. oocysts were found in
      feces at seven of nine sites, and Giardia cysts were found at all nine sites. The
      oocysts from three sites were infectious for mice and molecularly identified as
      the zoonotic genotype of Cryptosporidium parvum. Waterfowl can disseminate
      infectious C. parvum oocysts in the environment.

PMID- 9647861
TI  - Microbial community changes in a perturbed agricultural soil investigated by
      molecular and physiological approaches.
AB  - Changes in soil microbial activity and diversity after incubation either with
      nitrogen or with a mixture of methane and air were examined. The perturbation by
      methane and air were characterized in detail and led to reduced diversity and
      enrichment of methanotrophs which were identified by denaturing gradient gel
      electrophoresis and 16S rRNA sequencing.

PMID- 9647862
TI  - Importance of Extracellular Polymeric Substances from Thiobacillus ferrooxidans
      for Bioleaching.
AB  - Leaching bacteria such as Thiobacillus ferrooxidans attach to pyrite or sulfur by
      means of extracellular polymeric substances (EPS) (lipopolysaccharides). The
      primary attachment to pyrite at pH 2 is mediated by exopolymer-complexed
      iron(III) ions in an electrochemical interaction with the negatively charged
      pyrite surface. EPS from sulfur cells possess increased hydrophobic properties
      and do not attach to pyrite, indicating adaptability to the substrate or
      substratum.

PMID- 9647863
TI  - Gene cloning and characterization of a novel cellulose-binding beta-glucosidase
      from Phanerochaete chrysosporium.
AB  - Analysis of a 2.4-kb cDNA of the cellulose-binding extracellular beta-glucosidase
      (CBGL) from Phanerochaete chrysosporium suggested that CBGL is organized into two
      domains, an N-terminal cellulose-binding domain and a C-terminal catalytic
      domain. Genomic sequence analysis suggested that cbgl is encoded by 30 exons.
      Southern analysis of DNA from homokaryotic cultures indicated that CBGL is
      encoded by two alleles, cbgl-1 and cbgl-2, of a single gene.

PMID- 9647864
TI  - Microbial characterization of biological filters used for drinking water
      treatment.
AB  - The impact of preozonation and filter contact time (depth) on microbial
      communities was examined in drinking water biofilters treating Ohio River water
      which had undergone conventional treatment (coagulation, flocculation,
      sedimentation) or solutions of natural organic matter isolated from groundwater
      (both ozonated and nonozonated). With respect to filter depth, compared to
      filters treating nonozonated waters, preozonation of treated water led to greater
      differences in community phospholipid fatty acid (PLFA) profiles, utilization of
      sole carbon sources (Biolog), and arbitrarily primed PCR fingerprints. PLFA
      profiles indicated that there was a shift toward anaerobic bacteria in the
      communities found in the filter treating ozonated water compared to the
      communities found in the filter treating nonozonated settled water, which had a
      greater abundance of eukaryotic markers.

PMID- 9647865
TI  - Basic guide to the mechanisms of antiestrogen action.
AB  - Forty years ago, Lerner and coworkers (1958) discovered the first nonsteroidal
      antiestrogen and Jensen (Jensen and Jacobson, 1960) identified a target for drug
      action, the ER. This knowledge opened the door for the clinical development of
      tamoxifen which we now know provides a survival advantage in both node-positive
      and node-negative patients with ER-positive disease (Early Breast Cancer
      Trialists Collaborative Group, 1992, 1998). The drug has been studied
      extensively, and the results have provided an invaluable insight into possible
      ancillary advantages of "antiestrogens", i.e., maintenance of bone density and
      the prevention of coronary heart disease, and possible disadvantages, i.e., rat
      liver carcinogenesis and an increased risk of endometrial cancer. Most
      importantly, the identification of the target site-specific actions of tamoxifen
      caused a paradigm shift in the prospective uses of antiestrogens from a direct
      exploitation of the antitumor properties to the broader application as a
      preventative for osteoporosis, but with the beneficial side effects of preventing
      breast and endometrial cancer. Raloxifene, a second-generation SERM, has all the
      properties in the laboratory that would encourage development as a safe
      preventative for osteoporosis (Jordan et al., 1997). As a result, raloxifene has
      been evaluated in more than 11,000 postmenopausal women and found to maintain
      bone density with significant decreases in breast cancer incidence and no
      increase in endometrial thickness. Raloxifene is now available as a preventative
      for osteoporosis in postmenopausal women. There is every reason to believe that a
      multifaceted agent like raloxifene will find widespread use, and there will be
      continuing interest by the pharmaceutical industry in the development of new
      agents with even broader applications. The extensive clinical effort is augmented
      by past molecular innovations in the laboratory and the future promise of new
      discoveries. The cloning and sequencing of the ER (Green et al., 1986; Greene et
      al., 1986) has allowed the development of an ER knock-out mouse (Lubahn et al.,
      1993) that compliments Jensen's pioneering work (Jensen and Jacobson, 1962) and
      describes the consequences of the loss of ER alpha. However, ER beta (Kuiper et
      al., 1996), the second ER, has provided an additional dimension to the
      description of estrogen and antiestrogen action. For the future, the development
      of ER beta monoclonal antibodies, the classification of target sites for the
      protein around the body, and the creation of ER beta and ER alpha, beta knock-out
      mice will identify new therapeutic targets to modulate physiological functions.
      Clearly, the successful crystallization of ER alpha with raloxifene (Brzozowski
      et al., 1997) must act as a stimulus for the crystallization of ER beta. The
      central issue for research on antiestrogen pharmacology is the discovery of the
      mechanism (or mechanisms) of target site-specificity for the modulation of
      estrogenic and antiestrogenic response. The description of a stimulatory pathway
      for antiestrogens through an AP-1 ER beta signal transduction pathway (Paech et
      al., 1997), although interesting, may not entirely explain the estrogenicity of
      antiestrogens. The model must encompass the sum of pharmacological consequences
      of signal transduction through ER alpha and ER beta with the simultaneous
      competition from endogenous estrogens at both sites. This is complicated because
      estradiol is an antagonist at ER beta through AP-1 sites (Paech et al., 1997), so
      this is clearly not the pathway for estrogen-induced bone maintenance in women.
      Estrogen is stimulatory through ER alpha, but antiestrogens are usually partial
      agonists and may either block or stimulate genes. However, we suggest that the ER
      alpha stimulatory pathway could be amplified through selective increases in
      coactivators. The principle is illustrated with the MDA-MB-231 cells stably
      transfected with the cDNAs for the wild-type and the amino acid 351 mutan

PMID- 9647866
TI  - Signal transduction and signal modulation by cell adhesion receptors: the role of
      integrins, cadherins, immunoglobulin-cell adhesion molecules, and selectins.

PMID- 9647867
TI  - International Union of Pharmacology. XVIII. Nomenclature of receptors for
      vasoactive intestinal peptide and pituitary adenylate cyclase-activating
      polypeptide.

PMID- 9647868
TI  - International Union of Pharmacology. XIX. The IUPHAR receptor code: a proposal
      for an alphanumeric classification system.

PMID- 9647869
TI  - International Union of Pharmacology. XVII. Classification of muscarinic
      acetylcholine receptors.

PMID- 9647870
TI  - International Union of Pharmacology. XV. Subtypes of gamma-aminobutyric acidA
      receptors: classification on the basis of subunit structure and receptor
      function.

PMID- 9647871
TI  - Retinoid metabolism in the skin.

PMID- 9647872
TI  - The effects of self-administering emergency contraception.
AB  - BACKGROUND: Emergency postcoital contraception prevents pregnancy, but it must be
      prescribed by a doctor and taken within 72 hours of intercourse. It has been
      proposed that emergency contraception be made available without a prescription.
      We undertook a study to learn how women might behave if given a supply of
      emergency contraceptive pills to keep at home. METHODS: We assigned 553 women to
      be given a replaceable supply of hormonal emergency contraceptive pills to take
      home (the treatment group) and 530 women to use emergency contraception obtained
      by visiting a doctor (the control group). The frequency of use of emergency
      contraception, the use of other contraceptives, and the incidence of unwanted
      pregnancy were determined in both groups of women one year later. RESULTS: The
      results for 549 women in the treatment group and 522 women in the control group
      were available for analysis. Three hundred seventy-nine of the women in the
      treatment group (69 percent) and 326 of the women in the control group (62
      percent) contributed detailed information at follow-up. One hundred eighty of the
      women in the treatment group (47 percent) used emergency contraception at least
      once. Among those who returned the study questionnaire, 98 percent used emergency
      contraception correctly. There were no serious adverse effects. Eighty-seven
      women in the control group (27 percent) used emergency contraception at least
      once (P<0.001 for the comparison with the treatment group). The women in the
      treatment group were not more likely to use emergency contraception repeatedly.
      Their use of other methods of contraception was no different from that of the
      women in the control group. There were 18 unintended pregnancies in the treatment
      group and 25 in the control group (relative risk, 0.7; 95 percent confidence
      interval, 0.4 to 1.2). CONCLUSIONS: Making emergency contraception more easily
      obtainable does no harm and may reduce the rate of unwanted pregnancies.

PMID- 9647873
TI  - Prevention of a first stroke by transfusions in children with sickle cell anemia
      and abnormal results on transcranial Doppler ultrasonography.
AB  - BACKGROUND: Blood transfusions prevent recurrent stroke in children with sickle
      cell anemia, but the value of transfusions in preventing a first stroke is
      unknown. We used transcranial Doppler ultrasonography to identify children with
      sickle cell anemia who were at high risk for stroke and then randomly assigned
      them to receive standard care or transfusions to prevent a first stroke. METHODS:
      To enter the study, children with sickle cell anemia and no history of stroke had
      to have undergone two transcranial Doppler studies that showed that the time
      averaged mean blood-flow velocity in the internal carotid or middle cerebral
      artery was 200 cm per second or higher. The patients were randomly assigned to
      receive standard care or transfusions to reduce the hemoglobin S concentration to
      less than 30 percent of the total hemoglobin concentration. The incidence of
      stroke (cerebral infarction or intracranial hemorrhage) was compared between the
      two groups. RESULTS: A total of 130 children (mean [+/-SD] age, 8.3+/-3.3 years)
      were enrolled; 63 were randomly assigned to receive transfusions and 67 to
      receive standard care. At base line, the transfusion group had a slightly lower
      mean hemoglobin concentration (7.2 vs. 7.6 g per deciliter, P=0.001) and
      hematocrit (20.4 vs. 21.7 percent, P=0.002). Ten patients dropped out of the
      transfusion group, and two patients crossed over from the standard-care group to
      the transfusion group. There were 10 cerebral infarctions and 1 intracerebral
      hematoma in the standard-care group, as compared with 1 infarction in the
      transfusion group -- a 92 percent difference in the risk of stroke (P<0.001).
      This result led to the early termination of the trial. CONCLUSIONS: Transfusion
      greatly reduces the risk of a first stroke in children with sickle cell anemia
      who have abnormal results on transcranial Doppler ultrasonography.

PMID- 9647874
TI  - Effects of diet and exercise in men and postmenopausal women with low levels of
      HDL cholesterol and high levels of LDL cholesterol.
AB  - BACKGROUND: Guidelines established by the National Cholesterol Education Program
      (NCEP) promote exercise and weight loss for the treatment of abnormal lipoprotein
      levels. Little is known, however, about the effects of exercise or the NCEP diet,
      which is moderately low in fat and cholesterol, in persons with lipoprotein
      levels that place them at high risk for coronary heart disease. METHODS: We
      studied plasma lipoprotein levels in 180 postmenopausal women, 45 through 64
      years of age, and 197 men, 30 through 64 years of age, who had low high-density
      lipoprotein (HDL) cholesterol levels (< or =59 mg per deciliter in women and < or
      =44 mg per deciliter in men) and moderately elevated levels of low-density
      lipoprotein (LDL) cholesterol (>125 mg per deciliter but <210 mg per deciliter in
      women and >125 mg per deciliter but <190 mg per deciliter in men). The subjects
      were randomly assigned to aerobic exercise, the NCEP Step 2 diet, or diet plus
      exercise, or to a control group, which received no intervention. RESULTS: Dietary
      intake of fat and cholesterol decreased during the one-year study (P<0.001), as
      did body weight, in women and men in either the diet group or the diet-plus
      exercise group, as compared with the controls (P<0.001) and the exercise group
      (P<0.05), in which dietary intake and body weight were unchanged. Changes in HDL
      cholesterol and triglyceride levels and the ratio of total to HDL cholesterol did
      not differ significantly among the treatment groups, for subjects of either sex.
      The serum level of LDL cholesterol was significantly reduced among women (a
      decrease of 14.5+/-22.2 mg per deciliter) and men (a decrease of 20.0+/-17.3 mg
      per deciliter) in the diet-plus-exercise group, as compared with the control
      group (women had a decrease of 2.5+/-16.6 mg per deciliter, P<0.05; men had a
      decrease of 4.6+/-21.1 mg per deciliter, P<0.001). The reduction in LDL
      cholesterol in men in the diet-plus-exercise group was also significant as
      compared with that among the men in the exercise group (3.6+/-18.8 mg per
      deciliter, P<0.001). In contrast, changes in LDL cholesterol levels were not
      significant among the women (a decrease of 7.3+/-18.9 mg per deciliter) or the
      men (10.8+/-18.8 mg per deciliter) in the diet group, as compared with the
      controls. CONCLUSIONS: The NCEP Step 2 diet failed to lower LDL cholesterol
      levels in men or women with high-risk lipoprotein levels who did not engage in
      aerobic exercise. This finding highlights the importance of physical activity in
      the treatment of elevated LDL cholesterol levels.

PMID- 9647875
TI  - Chemotherapy alone compared with chemotherapy plus radiotherapy for localized
      intermediate- and high-grade non-Hodgkin's lymphoma.
AB  - BACKGROUND: Patients with clinically localized, intermediate- or high-grade non
      Hodgkin's lymphoma usually receive initial treatment with a doxorubicin
      containing regimen such as cyclophosphamide, doxorubicin, vincristine, and
      prednisone (CHOP). Pilot studies suggest that eight cycles of CHOP alone or three
      cycles of CHOP followed by involved-field radiotherapy are effective in such
      patients. METHODS: We compared these two approaches in a prospective, randomized,
      multi-institutional study. The end points were progression-free survival, overall
      survival, and life-threatening or fatal toxic effects. Two hundred eligible
      patients were randomly assigned to receive CHOP plus radiotherapy, and 201
      received CHOP alone. RESULTS: Patients treated with three cycles of CHOP plus
      radiotherapy had significantly better progression-free survival (P=0.03) and
      overall survival (P=0.02) than patients treated with CHOP alone. The five-year
      estimates of progression-free survival for patients receiving CHOP plus
      radiotherapy and for patients receiving CHOP alone were 77 percent and 64
      percent, respectively. The five-year estimates of overall survival for patients
      receiving CHOP plus radiotherapy and for patients receiving CHOP alone were 82
      percent and 72 percent, respectively. The adverse effects included one death in
      each treatment group. Life-threatening toxic effects of any type were seen in 61
      of 200 patients treated with CHOP plus radiotherapy and in 80 of 201 patients
      treated with CHOP alone (P=0.06). The left ventricular function was decreased in
      seven patients who received CHOP alone, whereas no cardiac events were recorded
      in the group receiving CHOP plus radiotherapy (P=0.02). CONCLUSIONS: Three cycles
      of CHOP followed by involved-field radiotherapy are superior to eight cycles of
      CHOP alone for the treatment of localized intermediate- and high-grade non
      Hodgkin's lymphoma.

PMID- 9647876
TI  - Aberrant interleukin-1 receptors in a cortisol-secreting adrenal adenoma causing
      Cushing's syndrome.

PMID- 9647877
TI  - Images in clinical medicine. Budding of human immunodeficiency virus.

PMID- 9647878
TI  - Acute human immunodeficiency virus type 1 infection.

PMID- 9647879
TI  - Self-administered emergency contraception--a second chance.

PMID- 9647880
TI  - Sickle cell disease--new treatments, new questions.

PMID- 9647881
TI  - Chemoradiotherapy for localized non-Hodgkin's lymphoma.

PMID- 9647882
TI  - Environmental health, risk assessment, and democracy.

PMID- 9647883
TI  - Protective role of stress genes.

PMID- 9647884
TI  - Vapor recovery systems can reduce risks from MTBE.

PMID- 9647885
TI  - Endocrine disruptors and testis development.

PMID- 9647887
TI  - Loud--but not yet clear.

PMID- 9647886
TI  - The first synthetic estrogen.

PMID- 9647888
TI  - Studies shed light on sunscreen efficacy.

PMID- 9647889
TI  - Researchers ready rapid Pfiesteria tests.

PMID- 9647890
TI  - NIEHS seeks data on multiple chemical sensitivity.

PMID- 9647891
TI  - Agreement on pork problems.

PMID- 9647892
TI  - New approaches for detecting thresholds of human nephrotoxicity using cadmium as
      an example.
AB  - Damage to the kidneys is one of the primary toxic actions of metals. Nephrotoxic
      substances not only cause renal disease directly, but they can also destroy renal
      reserve capacity, potentially placing those people with additional risk factors,
      such as diabetes, hypertension, cardiovascular disease, and genetic
      predispositions, at greater risk. To detect nephrotoxicity in people at a stage
      where intervention can be effective, sensitive methods are needed. One of the
      major advantages of using sensitive biomarkers of renal damage is that people who
      may be particularly susceptible to renal damage can be identified early, at a
      reversible stage of damage, and the progression to end-stage renal disease may be
      halted or delayed. Various categories of tests can be used to detect effects of
      nephrotoxic substances on the kidney. Through the use of biomarkers of damage to
      various parts of the nephron, U.S. and European studies have both shown a similar
      pattern of damage among men occupationally exposed to cadmium. These studies
      indicate various thresholds of renal effects, which researchers suggest represent
      a cascade of progressively severe damage to the kidney. Research into new
      biomarkers of damage caused by exposure to nephrotoxic substances centers around
      mechanisms of cell death, including necrosis and apoptosis; mechanisms of cell
      growth, regeneration, and proliferation, including factors that control cell
      cycle, influence gene expression, and modulate nucleic acid synthesis; and
      genetic factors that increase susceptibility to renal disease. Examples of types
      of candidate biomarkers include cytokines, lipid mediators, growth factors,
      transcription factors and protooncogenes, extracellular matrix components
      (collagen, glycoproteins, and proteoglycans), and cell adhesion molecules.
      Research into new categories of biomarkers may provide additional insights into
      the mechanisms of damage caused by nephrotoxins.

PMID- 9647893
TI  - Genetic influences on smoking: candidate genes.
AB  - Twin studies consistently indicate important genetic influences on multiple
      aspects of smoking behavior, including both initiation and cessation; however,
      knowledge regarding the role of specific genes is extremely limited. Habit
      forming actions of nicotine appear to be triggered primarily at nicotinic
      receptors on the cell bodies of dopaminergic neurons in the mesolimbic "reward"
      system of the brain, a region implicated in addiction to other substances
      including cocaine, opiates, and alcohol. Important aspects of the dopaminergic
      pathway include synthesis of dopamine in dopaminergic neurons, release of
      dopamine by presynaptic neurons, receptor activation of postsynaptic neurons,
      dopamine re-uptake by presynaptic neurons, and metabolism of released dopamine.
      Research examining the role of allelic variation in genes involved in these
      functions is being actively pursued with respect to addictive behavior as well as
      personality traits and psycho- and neuropathologic conditions and has
      implications for smoking research. In addition, genetic differences in nicotinic
      receptors or nicotine metabolism might reasonably be hypothesized to play a role
      in smoking addiction. A role of dopaminergic or other genes in smoking cessation
      is of particular potential importance, as research in this area may lead to the
      identification of subgroups of individuals for whom pharmacologic cessation aids
      may be most effective.

PMID- 9647894
TI  - Forms and prevalence of intersexuality and effects of environmental contaminants
      on sexuality in cricket frogs (Acris crepitans).
AB  - Cricket frogs (Acris crepitans) from several different sites in Illinois were
      collected to assess the effects of environmental contamination on the prevalence
      of intersex gonads. Of 341 frogs collected in 1993, 1994, and 1995, 2.7% were
      intersex individuals. There was no statistically significant relationship between
      the chemical compounds detected and cricket frog intersexuality. However, there
      was an association approaching significance (p = 0.07) between the detection of
      atrazine and intersex individuals. A comparison of reference sites with sites
      that had point polychlorinated biphenyl (PCB) and polychlorinated dibenzofuran
      (PCDF) contamination revealed a significant relationship between sex-ratio
      reversal and contamination with PCBs and PCDFs. The sex ratio of juvenile frogs
      studied from three sites with PCB and PCDF point contamination favored males over
      females, which was the opposite of the sex ratio in control ponds (p = 0.0007).
      The statistically significant correlation between organochlorine contamination
      and sex-ratio reversal suggests PCBs and PCDFs can influence cricket frog sexual
      differentiation. The current study suggests that in cricket frogs, sex ratios and
      the prevalence of intersex gonads are altered by environmental contamination.

PMID- 9647895
TI  - Discovering AIDS.

PMID- 9647896
TI  - Does the study of environmental disease determinants call for skepticism or open
      mindedness?

PMID- 9647897
TI  - The decomposition method.

PMID- 9647898
TI  - Constipation and colon cancer.

PMID- 9647899
TI  - Cancer among a Michigan cohort exposed to polybrominated biphenyls in 1973.
AB  - The long-term health effects of human exposure to polybrominated biphenyls are
      not known. In this nested case-control study, we evaluated the association
      between site-specific cancer risk and serum polybrominated biphenyl levels among
      a Michigan cohort accidentally exposed to polybrominated biphenyls in 1973. The
      Michigan Department of Public Health has followed 3,899 people through 1993,
      among whom 195 primary cancers were identified in 187 persons. Controls were 696
      randomly selected cancer-free individuals who were frequency matched to cases by
      sex and age (in 5-year strata). Baseline serum polybrominated biphenyl levels
      were measured using standard methods. We found an increasing dose-response
      relation for digestive system cancer risk with higher serum polybrominated
      biphenyl category [4-20 parts per billion (ppb), 21-50 ppb, and > 50 ppb] after
      adjustment for age, family cancer history, cigarette smoking, alcohol drinking,
      and baseline serum polychlorinated biphenyl level. Adjusted odds ratios (ORs) for
      each category were 8.23 [95% confidence interval (CI) = 1.27-53.3], 12.3 (95% CI
      = 0.80-191), and 22.9 (95% CI = 1.34-392), respectively. Univariate analysis for
      polybrominated biphenyl level and lymphoma risk also showed a dose-response
      relation, with corresponding ORs of 3.24 (95% CI = 0.24-95.9), 20.5 (95% CI =
      1.51-608), and 32.6 (95% CI = 3.33-861).

PMID- 9647900
TI  - Are female drivers safer? An application of the decomposition method.
AB  - Using the decomposition method and national data for the year 1990, we examined
      gender and age differences in involvement rates in fatal motor vehicle crashes.
      The fatal crash involvement rate per driver is expresses as a multiplicative
      function of the crash fatality rate (defined as the proportion of fatal crashes
      involved among all crashes involved), crash incidence density (that is, number of
      crashes per million person-miles), and exposure prevalence (that is, annual
      average miles driven per driver). The fatal crash involvement rate per 10,000
      drivers for men was three times that for women (5.3 vs 1.7) and was highest among
      teenagers. Of the male-female discrepancy in the fatal crash involvement rates,
      51% was attributed to the difference between sexes in crash fatality rates, 41%
      to the difference in exposure prevalence, and 8% to the difference in crash
      incidence density. Age-related variations in the fatal crash involvement rates
      resulted primarily from the differences in crash incidence density. The results
      indicate that, despite having lower fatal crash involvement rates, female drivers
      do not seem to be safer than their male counterparts when exposure is considered.
      The decomposition method is valuable as both a conceptual framework and an
      exploratory tool for understanding the contributing factors related to cause
      specific injury mortality and the differences in death rates among populations.

PMID- 9647901
TI  - Constipation, laxative use, and colon cancer among middle-aged adults.
AB  - We examined the associations of colon cancer with constipation and the use of
      commercial laxatives in a case-control study among men and women ages 30-62
      years. We based this analysis on 424 incident cases of colon cancer, diagnosed in
      the Seattle metropolitan area between 1985 and 1989, and 414 random-digit-dial
      controls. Frequent constipation during the 10 years before the reference data (2
      years before diagnosis), as defined by "feeling constipated to the point of
      having to take something," was associated with substantially increased risk of
      colon cancer. The adjusted relative risk (RR) was 2.0 [95% confidence interval
      (CI) = 1.2-3.6] for constipation 12-51 times per year, and 4.4(95% CI = 2.1-8.9)
      for constipation 52 or more times a year. Cumulative lifetime use of commercial
      laxatives was also associated with increased risk of colon cancer. When
      constipation and commercial laxative use were adjusted for each other, the
      association with commercial laxative use disappeared, whereas the association
      with constipation remained strong. Although constipation has not consistently
      been associated in past studies with a large increase in risk of colon and rectal
      cancer combined, these results suggest that frequent constipation may be an
      important risk factor for colon cancer among middle-aged adults.

PMID- 9647902
TI  - Magnetic fields and breast cancer in Swedish adults residing near high-voltage
      power lines.
AB  - We conducted a case-control study to test the hypothesis that residential
      magnetic field exposures increase the incidence of breast cancer. The study was
      based on people who had lived within 300 m of 220- or 400-kV power lines in
      Sweden at any time between 1960 and 1985. We identified 699 cases of breast
      cancer in women and 9 cases in men. One matched control per female case and eight
      per male case were selected at random. Estrogen receptor information was
      available for a subset of female cases. We assessed magnetic field exposure
      through calculations of the magnetic fields generated by the power lines before
      diagnosis. For calculated magnetic field levels > or = 0.2 microtesla (microT)
      closest in times before diagnosis, we estimated the relative risk to be 1.0 [95%
      confidence interval (CI) = 0.7-1.5] for women and 2.1 (95% CI = 0.3-14.1) for
      men. Women younger than 50 years of age at diagnosis had a relative risk of 1.8
      (95% CI = 0.7-4.3). For women with estrogen receptor-positive breast cancer, the
      relative risk was estimated at 1.6 (95% CI = 0.6-4.1), using the exposure cutoff
      point > or = 0.1 microT. Among estrogen receptor-positive women younger than 50
      years at diagnosis, the relative risk increased to 7.4 (95% CI = 1.0-178.1).

PMID- 9647903
TI  - Magnetic field exposure and neurodegenerative disease mortality among electric
      utility workers.
AB  - Several recent reports indicate that occupational exposure to electric and
      magnetic fields may be associated with increased risk of neurodegenerative
      diseases. To address that hypothesis, we analyzed data from a cohort study of
      electric utility workers. We examined exposure to magnetic fields, assessed as
      duration of work in exposed jobs and through an index of cumulative exposure
      based on magnetic field measurements, in relation to mortality from Alzheimer's
      disease, Parkinson's disease, and amyotrophic lateral sclerosis, considering both
      underlying and all mentioned causes of death. Adjusted mortality rate ratios
      based on Poisson regression models indicate no association between magnetic
      fields and Parkinson's disease and little support for an association with
      Alzheimer's disease mortality. Mortality from amyotrophic lateral sclerosis was
      positively associated with duration of work in exposed jobs [rate ratio = 2.0,
      95% confidence interval (CI)= 0.7-6.0; and rate ratio = 3.1, 95% CI = 1.0-9.8,
      based on underlying cause for 5 - < 20 years and > or = 20 years vs < 5 years,
      respectively], as well as with cumulative magnetic field exposure with a > or =
      20-year lag (rate ratio = 2.3, 95% CI = 0.8-6.6; and rate ratio = 3.0, 95% CI =
      1.0-9.2, for exposure in the middle and upper intervals relative to the lowest
      interval, respectively).

PMID- 9647904
TI  - Associations between lung function and estimated average exposure to NO2 in eight
      areas of Switzerland. The SAPALDIA Team. Swiss Study of Air Pollution and Lung
      Diseases in Adults.
AB  - In this paper, we present results from the SAPALDIA study (Swiss Study on Air
      Pollution and Lung Diseases in Adults) regarding associations between lung
      function [forced vital capacity (FVC) and forced expiratory volume in 1 second
      (FEV1)], as assessed during the cross-sectional study in 1991, and average levels
      of NO2 exposure within the eight study communities. We distinguished average home
      outdoor exposure and average personal exposure to NO2 and obtained exposure
      estimates by computing regional averages of passive sampler measurements
      performed by a random subsample of SAPALDIA participants in 1993. Previous
      analyses had revealed associations between average lung function and average air
      pollution levels between communities. The present results show that such
      associations may also be seen within communities: a 10-micrograms per m3 increase
      in average home outdoor and personal exposure to NO2 between zones of residence
      of the same community was associated with a change in average FVC by -0.59% [95%
      confidence limits (CL) = 0.01, -1.19] and -0.74% (95% CL = -0.07, -1.41),
      respectively. These values, however, are smaller than the ones found for the
      corresponding associations between study communities: -1.67% (95% CL = -1.01, 
      2.33) and -2.93% (95% CL = -2.11, -3.75), respectively. The different magnitudes
      of these two types of associations might be explained by differences in spatial
      variation between various components of air pollution.

PMID- 9647905
TI  - Use of toenail fluoride levels as an indicator for the risk of hip and forearm
      fractures in women.
AB  - The relation between fluoride intake and risk of osteoporotic fractures remains
      unclear. The lack of individual measures of long-term fluoride intake has limited
      epidemiologic studies. We used toenail fluoride in this study as a measure of
      long-term intake to evaluate the relation between fluoride intake and subsequent
      risk of hip and distal forearm fractures. Between 1982 and 1984, we collected
      toenail clippings from 62,641 women in the Nurses' Health Study who were free
      from cancer, heart disease, stroke, and previous hip or forearm fracture. We
      identified fracture cases (53 proximal femur and 188 distal forearm) through
      subsequent biennial mailed questionnaires and matched controls to cases on year
      of birth. The odds ratio of hip fracture among women in the highest quartile of
      toenail fluoride [ > 5.50 parts per million (ppm)], compared with those in the
      lowest quartile (> 2.00 ppm), was 0.8 (95% confidence interval = 0.2-4.0), with
      adjustment for menopausal status, postmenopausal hormone use, caffeine intake,
      and alcohol consumption. The corresponding adjusted odds ratio for forearm
      fracture was 1.6 (95% confidence interval = 0.8-3.1). Further adjustment for body
      mass index, smoking status, and calcium and vitamin D intake did not alter these
      results.

PMID- 9647906
TI  - Risk factors for fractures in the elderly.
AB  - We report the results of a 5-year prospective cohort study of risk factors for
      fractures, including drinking fluoridated water, in a cohort of 3,216 men and
      women aged 65 years and older. We studied risk factors for hip fracture and
      fractures at other locations separately. We found a higher risk of hip fractures
      for subjects exposed to fluorine concentrations over 0.11 mg per liter but
      without a dose-effect relation (odds ratio (OR) = 3.25 for a concentration of
      0.11-0.25 mg per liter; OR = 2.43 for > or = 0.25 mg per liter]. For higher
      thresholds (0.7 and 1 mg per liter), however, the OR was less than 1. We found no
      association between fluorine and non-hip fractures. Non-hip fractures were
      associated with polymedication rather than with specific drug use, whereas
      fracture was associated with polymedication and use of anxiolytic and
      antidepressive drugs. Subjects drinking spirits every day were more likely to
      have hip fractures. Tobacco consumption increased the risk for non-hip fractures.

PMID- 9647907
TI  - Mortality of aerospace workers exposed to trichloroethylene.
AB  - We measured mortality rates in a cohort of 20,508 aerospace workers who were
      followed up over the period 1950-1993. A total of 4,733 workers had occupational
      exposure to trichloroethylene. In addition, trichloroethylene was present in some
      of the washing and drinking water used at the work site. We developed a job
      exposure matrix to classify all jobs by trichloroethylene exposure levels into
      four categories ranging from "none" to "high" exposure. We calculated
      standardized mortality ratios for the entire cohort and the trichloroethylene
      exposed subcohort. In the standardized mortality ratio analyses, we observed a
      consistent elevation for nonmalignant respiratory disease, which we attribute
      primarily to the higher background rates of respiratory disease in this region.
      We also compared trichloroethylene-exposed workers with workers in the "low" and
      "none" exposure categories. Mortality rate ratios for nonmalignant respiratory
      disease were near or less than 1.00 for trichloroethylene exposure groups. We
      observed elevated rare ratios for ovarian cancer among those with peak exposure
      at medium and high levels] relative risk (RR) = 2.74; 95% confidence interval
      (CI) = 0.84-8.99] and among women with high cumulative exposure (RR = 7.09; 95%
      CI = 2.14-23.54). Among those with peak exposures at medium and high levels, we
      observed slightly elevated rate ratios for cancers of the kidney (RR = 1.89; 95%
      CI = 0.85-4.23), bladder (RR = 1.41; 95% CI = 0.52-3.81), and prostate (RR =
      1.47; 95% CI = 0.85-2.55). Our findings do not indicate an association between
      trichloroethylene exposure and respiratory cancer, liver cancer, leukemia or
      lymphoma, or all cancers combined.

PMID- 9647908
TI  - Factoring vs linear modeling in rate estimation: a simulation study of relative
      accuracy.
AB  - A common strategy for modeling dose-response in epidemiology is to transform
      ordered exposures and covariates into sets of dichotomous indicator variables
      (that is, to factor the variables). Factoring tends to increase estimation
      variance, but it also tends to decrease bias and thus may increase or decrease
      total accuracy. We conducted a simulation study to examine the impact of
      factoring on the accuracy of rate estimation. Factored and unfactored Poisson
      regression models were fit to follow-up study datasets that were randomly
      generated from 37,500 population model forms that ranged from subadditive to
      supramultiplicative. In the situations we examined, factoring sometimes
      substantially improved accuracy relative to fitting the corresponding unfactored
      model, sometimes substantially decreased accuracy, and sometimes made little
      difference. The difference in accuracy between factored and unfactored models
      depended in a complicated fashion on the difference between the true and fitted
      model forms, the strength of exposure and covariate effects in the population,
      and the study size. It may be difficult in practice to predict when factoring is
      increasing or decreasing accuracy. We recommend, therefore, that the strategy of
      factoring variables be supplemented with other strategies for modeling dose
      response.

PMID- 9647909
TI  - Accounting for time-dependent covariates whose levels are influenced by exposure
      status.
AB  - When measuring the association between an exposure and disease, one must decide
      whether to account for confounding or modifying variables whose levels are
      altered by the presence of the exposure. For example, to assess the impact of
      cessation of unopposed estrogen therapy on the occurrence of endometrial cancer,
      a researcher needs to consider the duration of the estrogen therapy, a strong
      risk factor for endometrial cancer, as a potential confounder or effect modifier.
      Duration of estrogen therapy, however, is itself influenced by the decision to
      stop the therapy (the "exposure" of interest). In such a case, two distinct
      approaches may be taken, depending upon the question being considered. One may
      wish to assess the degree to which the exposure predicts disease incidence, over
      and above the additional variable, at some later point in time. In this case, it
      is appropriate to consider the value of the other variable (for example,
      duration) at that later time. On the other hand, one may also wish to measure the
      rate of disease beginning at the time of cessation of the exposure, relative to
      the corresponding rate in persons with continuing exposure Here, the most
      appropriate analysis considers the level of the confounding variable (for
      example, duration) measured only until the time of exposure of interest occurs
      (for example, cessation of unopposed estrogen therapy). Examples are given to
      illustrate that the specific question being addressed dictates the handling of
      covariates of this type.

PMID- 9647910
TI  - The case-time-control design: further assumptions and conditions.
AB  - The case-time-control design is a strategy that was developed to tackle the
      problem of confounding by indication in the nonexperimental assessment of
      intended or known effects of drugs. By using subjects as their own controls, the
      case-time-control design, under an explicitly defined model, eliminates the
      biasing effect of unmeasured confounding factors in the situation where exposure
      varies over time. The correct application of this design is based on a specific
      model that contains inherent assumptions and imposes certain conditions for the
      approach to be valid. In a recent article, Greenland questioned the validity of
      the case-time-control design by presenting several "counterexamples." In this
      paper, we review the assumptions inherent to the validity of the case-time
      control model. We show that the presumed counterexamples are not what they are
      claimed to be, simply because they do not conform to the logistic model
      explicitly underlying the case-time-control approach. These examples are shown to
      arise from an alternative model that includes a confounder by period interaction,
      a term expressly avoided in the case-time-control model. When the data from these
      examples are modified to satisfy the correct model, the resulting case-time
      control estimates of the treatment odds ratio are exactly 2, the true treatment
      effect. We clarify the necessity of this assumption in the context of matching in
      epidemiology. We also discuss briefly the assumptions of conditional independence
      and carryover effects.

PMID- 9647911
TI  - Probability model on the use of sentinel animal monitoring for arbovirus.
AB  - We specify the relations among the major parameters involved in using sentinel
      animals to monitor arbovirus transmission. By using probability models, first we
      demonstrate that vector density, infection rate, incubation period of sentinel
      animals, the number of sentinel animals used, and blood sampling frequency could
      directly affect the observed seroconversion rates and the comparison of these
      rates. Second, we evaluate the reliability of using sentinel animals to monitor
      arbovirus transmission under various conditions. On the basis of the model, we
      propose some measures for enhancing the reliability of using sentinel animals to
      monitor arbovirus. Third, we present a formula for estimating the number of
      sentinel animals used for a study designed to compare seroconversion rates.
      Fourth, we derive a necessary condition for deciding the blood sample frequency
      of sentinel animals. Fifth, we develop a formula that could be used to obtain the
      vector infection rate by using seroconversion data. Finally, we evaluate the
      epidemiology consequences of heterogeneous exposure of human hosts to vectors by
      theoretical modeling.

PMID- 9647912
TI  - Comparison of mortality from peptic ulcer bleed between patients with or without
      peptic ulcer antecedents.
AB  - We studied mortality related to peptic ulcer bleed in a well defined cohort of
      patients in the month after the episode of peptic ulcer bleed. Our objective was
      to assess the contribution of peptic ulcer antecedents and other predictive
      factors on the risk of dying. The study cohort comprised 1,020 patients
      hospitalized for an episode of peptic ulcer bleed between January 1991 and March
      1994 and identified in the General Practice Research Database in the United
      Kingdom. Six hundred twenty-three patients had no prior episode of peptic ulcer
      disease, and 384 had peptic ulcer antecedents; for 13 patients, information was
      not available. Forty-five patients died (mortality rate = 4.4 per 100 person
      months; 95% confidence interval = 3.3-5.9) within 1 month of the peptic ulcer
      bleed. Patients with no peptic ulcer antecedent faced a greater risk of dying
      than patients with antecedents (relative risk = 3.0; 95% confidence interval =
      1.2-7.1). Elderly patients, those undergoing surgery, and current users of acid
      suppressing drugs or nonsteroidal antiinflammatory drugs all had an increased
      mortality risk. Patients presenting with their first-ever episode of peptic ulcer
      bleed have a higher case fatality rate than those with previous episodes of
      peptic ulcer.

PMID- 9647913
TI  - Vitamins in HIV disease progression and vertical transmission.
AB  - Human immunodeficiency virus (HIV) infection is a major public health problem
      worldwide, but particularly in subsaharan Africa and Asia. Numerous observational
      studies report inverse associations between vitamin status, measured
      biochemically or as levels of dietary intake, and the risk of disease progression
      or vertical transmission. Evidence to support these findings has been obtained
      from a few randomized placebo-controlled trials. In this paper, we review studies
      that examined the role of vitamins A, B, C, D, and E in HIV disease progression
      and transmission, and we discuss the potential mechanisms of action of these
      vitamins. Adequate vitamin intake leads to enhancement of epithelial integrity
      and systemic immunity and could contribute to improved clinical condition among
      HIV-infected subjects and reduce vertical transmission by reducing the risk and
      severity of opportunistic infection and reducing viral load in blood. Adequate
      vitamin status may also reduce vertical transmission through the intrapartum and
      breastfeeding routes by reducing HIV viral load in lower genital secretions and
      breast milk, respectively. Vitamin supplements may be one of a few potential
      treatments that are inexpensive enough to be made available to HIV-infected
      persons in developing countries.

PMID- 9647914
TI  - Inventing the AIDS virus hypothesis: an illustration of scientific vs
      unscientific induction.

PMID- 9647915
TI  - Diesel exhaust and lung cancer.

PMID- 9647916
TI  - Paternal dioxin and the sex of children fathered by veterans of Operation Ranch
      Hand.

PMID- 9647917
TI  - The residential case-specular method to study wire codes, magnetic fields, and
      disease.

PMID- 9647918
TI  - [Determination of the onset of stroke. Satellite Symposium: "Current Approaches
      to the Management of Acute Ischemic Stroke", within the framework of the "6th
      European Stroke Conference". Amsterdam, 28 May 1997].

PMID- 9647919
TI  - [The Danish concept of acoustic neuroma surgery: is it still current?].

PMID- 9647920
TI  - [Role of perimatrix fibroblasts in development of acquired middle ear
      cholesteatoma. A hypothesis].
AB  - The epithelial pathogenesis of acquired cholesteatoma has been widely accepted,
      but clinical and experimental data have not been able to answer questions like:
      How does a cholesteatoma start or grow or how is bone resorption of conducted?
      From our own experiments and literature a new hypothesis of cholesteatoma origin
      and growth is drawn. Three prerequisites are necessary for development: (1) the
      unique anatomical situation at the ear-drum (two different epithelial layers
      close together); (2) chronic destruction of the submucosal tissue in the middle
      ear (infection, inflammation); (3) wound healing (proliferation phase).
      Destruction of the submucosal space by middle ear infection and cell necrosis
      starts the wound healing cascade. In wound healing generally the connective
      tissue fibroblasts and macrophages play a pivotal role. Cytokines of the wound
      healing thought to promote the re-epithelization of the mucosal defect and scar
      tissue development act upon the intact squamous cell layer of the outer surface
      of the ear-drum at the same time. Thereby a proliferation of the undamaged
      epithelial layer is induced. Cholesteatoma matrix is always surrounded by a layer
      of connective tissue, the perimatrix. Persistence of the inflammation causes
      permanent wound healing in the perimatrix, proliferation of the fibroblasts
      (granulation tissue) and proliferation of the epithelium (matrix). It is
      speculated that by virtue of wound healing cytokines of fibroblasts and
      macrophages are the driving forces of cholesteatoma origin, growth and bone
      destruction.

PMID- 9647921
TI  - [Electron microscopy studies of the human vomeronasal organ].
AB  - The vomeronasal organ, or Jacobson's organ, is essential for pheromone detection
      and reproductive behavior in most mammals. In humans, it has been described as a
      blind diverticulum in the anterior nasal septum, but without a documented
      function. The purpose of this study is to describe the fine structure of the
      human adult vomeronasal organ in 14 specimens. Our studies showed a duct-like
      invagination of the epithelium that was surrounded by numerous exocrine glands
      with short ducts. The fine structure of these glands suggested a serous
      secretion. In the depth of the invagination, pseudostratified columnar epithelial
      cells were seen that had plump processes, kinocilia and microvilli at the apical
      cell membrane. Several cell types were seen that differed regarding their
      organelles and electron density, with light sensory cells exhibiting
      neurofilaments. Underneath the typical basement membrane, numerous myelinated and
      unmyelinated axons were present in the very vascular lamina proprion. These
      morphological findings are unique in the human body and suggest that a
      chemosensory epithelium corresponding to a vomeronasal organ may exist. Its
      central connections and the possible functional significance of this tubed organ
      for pheromone detection are unknown and need further study.

PMID- 9647922
TI  - [A micromanipulator for intraoperative vibratory hearing assessment with an
      implantable hearing aid transducer].
AB  - First concepts of implantable hearing aids to be coupled to the ossicular chain
      are available for patients with combined or sensorineural hearing loss (SNHL). To
      ensure that hearing can be improved intraoperative coupling of a test transducer
      to the ossicular chain is mandatory for allowing surgical anatomy to be checked
      and vibratory hearing tests to be performed. To achieve this, the test transducer
      has to be held and positioned securely in situ for some minutes, avoiding risks
      for middle or inner ear structures. This is not possible using conventional
      surgical instruments. Thus, a micromanipulator to hold the test transducer during
      intraoperative hearing tests was developed. This surgical device allows the
      surgeon safe, risk-free, and controlled coupling of the test transducer to the
      ossicular chain with one axial and three rotational degrees of freedom. With the
      aid of a conventional ear retractor (2x2 prongs), the manipulator is fixed at the
      patient's ear. In conjunction with a piezoelectric test transducer, the
      manipulator was used in nine patients during local anesthesia. The test
      transducer is part of an electronic hearing implant (Tubingen implant)
      specifically designed for SNHL that may be coupled to a middle ear ossicle or the
      perilymph of the cochlea. The micromanipulator was easy to handle. It allowed
      accurate positioning of the test transducer in the ear and the desired coupling
      of the transducer's probe tip to the ossicular chain during auditory tests.
      According to the principles of integrated safety, the intraoperative risk of
      ossicular or inner ear injuries caused, for instance, by the patient's head
      movement is minimized. The design of the manipulator system is universal, also
      allowing its use for other electronic hearing implants or minimal invasive
      surgery after minor modifications.

PMID- 9647923
TI  - [Frequency specificity of acoustic evoked potentials of early and intermediate
      latency with high-pass noise masking].
AB  - In contrast to auditory brainstem potentials (ABR), a more apically defined
      generation of middle latency evoked potentials (MLR) can be assumed due to the
      longer integration time present. To date, the effect of stimulus frequency
      spectra on MLR has not been completely known. By using masking with high-pass
      filtered white noise in 12 normal-hearing adults, we measured the dependence of
      amplitude and latency of ABR and MLR on filter frequency. No differences were
      found between the masking effects for ABR and MLR evoked by tone bursts of 0.5
      and 2 kHz. The high-pass masking of click stimuli showed a greater influence on
      the amplitude and latency of the ABR than on MLR. These different qualities have
      to be considered clinically when evaluating the methods and results of hearing
      testing with acoustic evoked potentials. Our findings show that MLR evoked by
      tone bursts should be used for the frequency selective diagnosis of hearing
      thresholds, especially in low-frequency ranges.

PMID- 9647924
TI  - [Rhinomanometric studies of thermal modification of nasal ventilation].
AB  - Elevation of nasal resistance has been described as an effect of increased air
      temperature by different authors. The aim of this study was to evaluate the
      effect of high environmental temperature on congestion of the nasal mucosa. In
      all, 102 volunteers were studied and included normal controls, heart
      rehabilitation patients and high performance sportsmen. Rhinomanometric
      examinations were carried out before and after 10 min in a dry Finnish sauna at a
      90 degrees C temperature. Computerized active anterior rhinomanometry was used. A
      uniform response pattern to the increased temperature could not be observed:
      i.e., some individuals had an elevated resistance immediately after the sauna
      while resistance was decreased in others. The relationship between the reaction
      of the nasal mucosa to body work and temperature is discussed.

PMID- 9647925
TI  - [Deafness: the right to silence or the chance to hear with a cochlear implant?
      Human images and medicine in the world of the deaf and in the world of the
      hearing].
AB  - Cochlear implantation has evolved from its experimental state into a safe and
      effective therapy for the treatment of profound deafness. Although not applicable
      to all patients, it offers an alternative to a life in silence. In particular, in
      early detected and treated deafness in childhood inner ear prostheses have
      enabled affected persons to be integrated into the world of sound. In addition to
      the significant impact that therapy has on the life of the individual, there is a
      social and cultural consequence for society. This is epitomized in the criticism
      by the deaf community that has resulted in the total rejection of cochlear
      implants. A critical analysis reveals different personal images prevailing in the
      deaf community. Knowledge of these differences and their relevance is important
      for all clinicians involved in counselling a cochlear implant candidate.

PMID- 9647926
TI  - [Acoustic rhinometry for evaluating the effectiveness of antihistaminics].
AB  - Acoustic rhinometry is a unique non-invasive technique for imaging and measuring
      the free cross-sectional area of the main nasal cavity. By so doing, reactions of
      the mucosa can be assessed at any selected site in the nose. The goal of this
      study was to define the optimal conditions for the utilization of acoustic
      rhinometry to determine the ability of an antihistamine to alter the effects of
      histamine in the mucous membrane of the nose. In a group of 30 healthy volunteers
      subjectively normal nasal breathing, and no history of allergy, rhinometry was
      performed to measure the cross-sectional area in the region of the head of the
      inferior nasal concha at 0.5, 10 and 15 min after histamine provocation. The
      volunteers subsequently received cetirizine as antihistamine. Four hours later,
      rhinometry was repeated after administration of histamine via the contralateral
      nostril. Findings showed that conchal dilatation measured 10 min after
      provocation was statistically less severe in 63.3% of the patients treated with
      cetirizine. Compared to pretreatment values, the ventilated cross-sectional area
      became 45.6% larger after administration antihistamine. These findings
      demonstrated that the nasal swelling measured 10 min after antihistamine
      administration was due to the effects of histamine and was not due to tactile or
      physical stimuli. The present studies showed that the new measurement technique
      is precise and reproducible. These results have also demonstrated that a acoustic
      rhinometry permits an objective assessment of drug efficacy while making it
      possible to avoid the errors observed in other variable regions of the nose, such
      as the nasal isthmus or nasopharynx as well as errors associated with subjective
      scoring systems.

PMID- 9647927
TI  - [Vascular middle ear structure. Ectopic course of the internal carotid artery].

PMID- 9647928
TI  - [Voice signal analysis in laryngeal hyperreactivity].
AB  - Increased reactions of the laryngeal mucosal membrane can appear after
      acetylcholine (ACH) inhalation. A red mucous membrane, vocal cord edema, mucus
      formation, changes in the glottic configuration and (rarely) subglottic edema are
      visible to laryngoscopic observations. The influence on various voice parameters
      in patients with and without laryngeal hyperreactivity was researched in order to
      decide the reliability of voice parameter measurements in clinical practice.
      Significant variations of the soft phonation index (SPI), the fundamental
      frequency variation (vFo), the noise-to-harmonic ratio (NHR) and the voice
      turbulence index (VTI) were examined for their correlations with the observable
      features of laryngeal hyperreactivity. A single diagnosis of hyperreactivity with
      voice parameter analysis failed in 50% of the patients examined because of
      functional voice instability and irregularities seen. Only with both laryngoscopy
      for reliable discrimination and voice parameter analysis for quantitative
      registration were findings sufficient for assessing laryngeal hyperreactivity.

PMID- 9647929
TI  - [Transglandular tumor of the parotid gland. Centroblastic-centrocytic lymphoma].

PMID- 9647930
TI  - [Lymphoma of the cerebellopontile angle as etiology of retrochochlear damage.
      Case report and review of the literature].
AB  - The clinical features of progression sensorineural hearing loss and vertigo in
      combination with the radiologic finding of a contrast-enhancing mass within the
      inner auditory canal are suggestive of an acoustic neuroma. We report our
      findings in a 57-year-old woman with known mixed connective tissue disease who
      was presumed to have a neuroma. A large malignant lymphoma of the
      cerebellopontine angle presented clinically with a primary acoustic none palsy
      and no other central neurological deficits. Both the primary radiological
      examinations and the exclusively peripheral nerve palsy failed to indicate
      manifestations of a lymphoma. The development of a progressive facial palsy
      within 8 weeks of presentation and an atypical occipital headache were uncommon
      findings for an acoustic neuroma. Such changes in symptoms despite the occurrence
      of cardinal symptoms require further diagnostic measures. Manifestations of a
      malignant lymphoma in the cerebellopontine angle are extremely rare. To our
      knowledge a case of an intracerebral lymphoma in a patient with Sjogren's
      syndrome has never been reported before.

PMID- 9647931
TI  - [Tracheal wall cyst. A rare cause of stridor in the adult].
AB  - A case of tracheal cyst is described in a 43-year-old man who was admitted with
      nonspecific symptoms of an obstruction in the upper respiratory tract. A CT scan
      of the thorax showed a solid tumor on the inner tracheal wall. Bronchoscopy
      revealed a tumor with a broad base and smooth surface that almost completely
      obstructed the trachea. Intraoperatively, the tumor was found to be a cyst and
      was successfully removed endoscopically. Tracheal cysts are quite rare and most
      of the reported cases have been confined to pediatric patients as a congenital
      disease. More frequently, congenital intraluminal cysts of the upper respiratory
      tract are found as epiglottic retention cysts and laryngoceles.

PMID- 9647932
TI  - [Indications for performing uvulopalatopharyngoplasty and laser-assisted
      uvulopalatopharyngoplasty].

PMID- 9647933
TI  - Sexual behavior of Flinders Line female rats bred for differential cholinergic
      sensitivities.
AB  - Flinders Lines are two strains of rats selectively bred for their divergent
      physiological responses to cholinergic drug challenges. Flinders Sensitive Line
      (FSL) rats are highly sensitive to cholinergic stimulation of various autonomic
      and behavioral responses compared to Flinders Resistant Line (FRL) rats. Because
      cholinergic innervation contributes to the regulation of female sexual behaviors
      in rats, a study was conducted to compare the sexual responses of FSL females to
      those of FRL females, as well as to those of Long-Evans (LE) females, a
      conventional rat strain. Ovariectomized FSL rats exhibited significantly higher
      incidences of lordosis and proceptive behaviors than ovariectomized FRL and LE
      rats over a range of estrogen doses (2, 3, 4, 5, or 20 microgram(s)/kg estradiol
      benzoate at 48 h before testing) administered in combination with progesterone (1
      or 2 mg/kg at 4-6 h before testing). In addition, the muscarinic antagonist
      scopolamine inhibited lordosis behavior strongly in FRL females over a range of
      doses (0.25, 0.5, 1, 2, or 4 mg/kg), but failed to inhibit lordosis in FSL
      females. Results indicate that FSL females are highly sensitive to the behavioral
      effects of gonadal steroids and highly insensitive to the effects of a muscarinic
      antagonist. The enhanced sexual behavioral responses of FSL females could be a
      consequence of their well-established cholinergic hypersensitivity or a
      consequence of other undocumented characteristics of FSL females such as
      hypersensitivity to ovarian hormones. FSL females could provide a valuable model
      for the study of estrogen action at behavioral, cellular, and molecular levels.

PMID- 9647934
TI  - Androgen-behavior correlations in hypogonadal men and eugonadal men. II.
      Cognitive abilities.
AB  - Sex-typed cognitive abilities were assessed in 33 hypogonadal men receiving
      testosterone replacement therapy, 10 eugonadal men receiving testosterone in a
      male contraceptive clinical trial, and 19 eugonadal men not administered
      testosterone. Prior to and following hormone administration, men completed four
      tests measuring visuospatial ability, three tests measuring verbal fluency, two
      tests measuring perceptual speed, and a measure of verbal memory. Group
      differences in testosterone levels were unrelated to performance on most
      cognitive measures, including visuospatial ability. Relative to other men,
      hypogonadal men were impaired in their verbal fluency and showed improved verbal
      fluency following treatment with testosterone. These data suggest that
      testosterone may enhance verbal fluency in hypogonadal men and support the
      general hypothesis that current levels of testosterone may influence some aspects
      of cognitive function.

PMID- 9647935
TI  - Estradiol increases female sexual initiation independent of male responsiveness
      in rhesus monkeys.
AB  - Copulation and female initiation of sexual behavior vary across the ovarian
      cycle, suggesting that female hormonal condition influences female sexual
      motivation in rhesus monkeys. However, the effects of hormones on female sexual
      motivation are difficult to identify because male behavior also varies with
      female hormonal condition. During the nonbreeding season, male rhesus monkeys are
      sexually unresponsive to females; thus the effects of estradiol treatment on
      female sexual motivation can be examined independent of male behavior. This study
      administered estradiol to five ovariectomized females living in a large age
      graded social group during the nonbreeding season. The behavior of these females
      with and without estradiol treatment was compared. Data were collected
      concurrently on five intact, noncycling, nonpregnant females. Estradiol treatment
      significantly increased sexual initiation by ovariectomized females toward males
      without any significant changes in male behavior. Estradiol-treated females also
      displayed greater sexual initiation than nonpregnant, intact females. Both
      estrogen and progesterone were important predictors of sexual initiation in
      females, with progesterone having an inhibitory effect. Endogenous progesterone
      levels in females were negatively correlated with male contact behavior,
      suggesting that female attractiveness is reduced by progesterone. This study
      provides further support for estrogen as the critical steroid increasing female
      sexual motivation in primates.

PMID- 9647936
TI  - Effects of pregnancy hormones on maternal responsiveness, responsiveness to
      estrogen stimulation of maternal behavior, and the lordosis response to estrogen
      stimulation.
AB  - The aim of the study was to determine whether there is an increase in
      responsiveness to estrogen stimulation of maternal behavior and lordosis
      responsiveness during pregnancy. Using separate groups of pregnancy-terminated
      females, we measured the initial maternal responsiveness of hysterectomized
      ovariectomized (HO) females and their responsiveness to estrogen stimulation.
      Maternal behavior latencies were studied in females HO on the 8th, 10th, 13th,
      16th, or 19th day of pregnancy (8HO-19HO) and in nonpregnant HO (NPHO) females.
      Groups were injected sc with estradiol benzoate (EB) in doses ranging from 0 to
      200 microgram(s)/kg and tested for maternal behavior (retrieving, crouching, and
      licking pups). In addition, we investigated whether there is an increase during
      pregnancy (following HO) in lordosis responsiveness to estrogen stimulation.
      Lordosis behavior was studied in pregnant HO females (days 8, 16, and 22) and
      NPHO females given 0 to 200 microgram(s)/kg EB. There was an increase in maternal
      responsiveness in oil-treated HO females starting around midpregnancy. From early
      pregnancy on there was also an increase in maternal responsiveness to 20
      microgram(s)/kg EB. In late pregnant females (16HO) there was a further increase
      with 50 microgram(s)/kg EB. There was no increase in lordosis responsiveness to
      EB stimulation during pregnancy; pregnant and nonpregnant HO females had the same
      EB threshold for stimulating lordosis behavior. The results of both studies were
      related to increases during the latter half of pregnancy in nuclear estrogen
      receptor concentrations in the MPOA, an area that mediates estrogen stimulation
      of maternal behavior, and the absence of such increases during pregnancy in the
      VMH, an area that mediates estrogen stimulation of lordosis behavior.

PMID- 9647937
TI  - Site-specific opioid receptor blockade allows prepubertal guinea pigs to display
      progesterone-facilitated lordosis.
AB  - Ovariectomized (OVX) juvenile guinea pigs (approximately 3 weeks old) rarely
      display steroid-induced sexual receptivity. Systemic administration of the opioid
      receptor antagonist naloxone enhances the display of progesterone-facilitated
      lordosis in prepubertal females, suggesting that endogenous opioids tonically
      inhibit the expression of sexual receptivity at this age. This study was designed
      to ascertain the neural site(s) at which naloxone injection would stimulate
      lordosis in juvenile guinea pigs. Hartley guinea pigs were OVX at 10-11 days of
      age and 2-6 days later implanted with bilateral cannulae aimed at the medial
      preoptic area/anterior hypothalamus (MPOA/AH), ventrolateral
      hypothalamus/ventromedial hypothalamus (VLH/VMH), or mesencephalic central gray
      (MCG). At 21-23 days of age, following administration of estradiol benzoate (10
      microgram(s)) and progesterone (0.5 mg), naloxone (100 ng/side) or 0.9% saline
      was injected through the cannulae and the guinea pigs were tested for the display
      of lordosis. The MPOA/AH was the only site at which application of naloxone
      reliably elicited lordosis (87% positive response vs 12% for saline). Few females
      (< 17%) displayed lordosis following injections of naloxone or saline into the
      VLH/VMH or MCG. A second experiment demonstrated that the stimulation of lordosis
      following MPOA/AH naloxone application was prevented by prior injection of the
      opioid agonist morphine (500 ng/side) at the same site. These data support the
      hypothesis that endogenous opioids acting in the MPOA/AH, but not the VLH/VMH or
      MCG, tonically inhibit the display of progesterone-facilitated lordosis in
      prepubertal guinea pigs.

PMID- 9647938
TI  - Fos induced by mating or noncontact sociosexual interaction is colocalized with
      androgen receptors in neurons within the forebrain, midbrain, and lumbosacral
      spinal cord of male rats.
AB  - This study was designed to determine the extent to which Fos immunoreactivity
      (induced either by mating or noncontact sociosexual interaction) and androgen
      receptor (AR) immunoreactivity are colocalized in brain and spinal cord of male
      rats. Some males (Mated) were allowed to mate to ejaculation; others (Social
      Controls) were placed with females but physical contact was prevented by a wire
      mesh screen; remaining males (Isolated) were placed alone in the test jar for the
      duration of the test period. After testing, brains and spinal cords were examined
      for AR and Fos immunoreactivity (ir). PG21 anti-AR and anti-c-fos primary
      antibodies were visualized by fluorescence microscopy using cyanine-conjugated
      and fluorescein-conjugated secondary antibodies. In both brain and spinal cord,
      the number of Fos-ir neurons varied according to group: Mated males > Social
      Controls > Isolated males. Fos was highly localized in subsets of AR-ir neurons
      within the medial preoptic nucleus, bed nucleus of the stria terminalis,
      dorsomedial nucleus of the amygdala, and central tegmental field. Fos was also
      localized in subsets of AR-ir neurons within the L5, L6, and S1 segments of the
      spinal cord. Spinal cord concentrations of AR-ir and Fos-ir neurons were greatest
      in Lamina X, and the vast majority of Fos-ir neurons in the dorsal part of Lamina
      X were also AR-ir. Thus, in both brain and spinal cord, androgen-sensitive
      neurons are active during mating, and transmission of sexually relevant
      information from cord to brain is probably accomplished via hormone-sensitive
      spinal neurons.

PMID- 9647939
TI  - Influence of stimuli from chicks on behavior and concentrations of plasma
      prolactin and luteinizing hormone in incubating hens.
AB  - Removal of eggs from the nests of incubating birds or substitution of eggs for
      chicks disrupts incubation behavior and induces changes in the secretion of
      prolactin and luteinizing hormone (LH). The aim of the present study was to
      determine how different stimuli, such as physical contact with eggs and tactile,
      visual, and/or auditory cues from chicks, interact to control the transition
      between incubation and brooding and to induce changes in prolactin and LH plasma
      concentrations. Physical contact with chicks, in the presence or absence of eggs,
      induced brooding behavior and an immediate fall in plasma prolactin concentration
      and a gradual increase in LH concentration. Vocalizations, particularly clucking
      and food calls, increased rapidly while incubation and nest attachment
      disappeared slowly. No change in plasma prolactin or LH concentration was
      observed in incubating hens which could hear and see or only hear chicks. These
      incubating hens showed no interest in chicks and continued to incubate
      persistently. To conclude, tactile stimuli, alone or in combination with visual
      and/or auditory stimuli from newly hatched chicks, are the only cues that induce
      the transition from incubation to brooding and the associated decrease in
      prolactin secretion and increase in LH secretion.

PMID- 9647940
TI  - Clinical safety of oral sildenafil citrate (VIAGRA) in the treatment of erectile
      dysfunction.
AB  - Sildenafil citrate has been shown to be effective in a wide range of patients
      with erectile dysfunction and has been approved in the United States for this
      indication. The overall clinical safety of oral sildenafil, a potent inhibitor of
      phosphodiesterase type 5, in the treatment of erectile dysfunction was evaluated
      in more than 3700 patients (with a total of 1631 years of exposure worldwide).
      Safety and tolerability data were analysed from a series of double-blind, placebo
      controlled studies and from 10 open-label extension studies of sildenafil in the
      treatment of erectile dysfunction. A total of 4274 patients (2722 sildenafil,
      1552 placebo; age range 19-87 y) received double-blind treatment over a period of
      up to six months' duration, and 2199 received long-term, open-label sildenafil
      for up to 1 y. The most commonly reported adverse events (all causes) were
      headache (16% sildenafil, 4% placebo), flushing (10% sildenafil, 1% placebo), and
      dyspepsia (7% sildenafil, 2% placebo) and they were predominantly transient and
      mild or moderate in nature. These adverse events reflect the pharmacology of
      sildenafil as a phosphodiesterase type 5 inhibitor. No cases of priapism were
      reported. The rate of discontinuation due to adverse events (all causes) was
      comparable for patients treated with sildenafil (2.5%) and placebo (2.3%). In
      open-label extension studies, 90% of patients completed long-term sildenafil
      treatment, with only 2% withdrawing due to adverse events. Sildenafil is a well
      tolerated oral treatment for erectile dysfunction.

PMID- 9647941
TI  - Does severity of ischaemic coronary disease correlate with erectile function?

PMID- 9647942
TI  - Development of an organ culture experimental system to investigate collagen
      synthesis in corpora cavernosa.
AB  - An organ culture model of rabbit corpus cavernosum has been developed to
      investigate fibrillar collagen synthesis in intact organ. Rabbit peni were
      removed en bloc, the corpora cavernosa were dissected, sliced into 5 mm pieces
      and incubated in culture media up to 24 h. Tissue viability and metabolic and
      functional integrity were assessed by (a) lactate dehydrogenase (LDH) release,
      (b) protein synthesis, and (c) ability to respond to exogenously added cytokines.
      Explants, maintained for 24 h in organ culture, exhibited minimal LDH release and
      maintained functional integrity determined from protein synthesis and ability to
      synthesize collagen in response to TGF-beta(1). These data suggest that explants
      of rabbit corpus cavernosum in organ culture represent a viable model to
      investigate connective tissue protein biosynthesis in vitro.

PMID- 9647943
TI  - The impact of marital satisfaction and psychological counselling on the outcome
      of ICI-treatment in men with ED.
AB  - We investigated the relationship between marital satisfaction and choice of and
      compliance with treatment in 195 consecutive men with erectile dysfunction (ED).
      Marital satisfaction as measured by means of the Maudsley Marital Questionnaire
      (MMQ), was compared between four groups: (1) patients on intracavernous injection
      (ICI) treatment after the trial-dose phase (32%); (2) patients dropped out ICI in
      the trial-dose phase (12%); (3) patients on other treatment (31%); and (4)
      patients following first counselling renounced treatment (25%). Above, in a small
      group of 15 patients the effect of ICI treatment in combination with short-term
      psychological counselling (ICI + treatment) was assessed. No significant
      differences were found in marital satisfaction between the four groups. In the
      ICI + treatment group we experienced that providing information about factors
      that contribute to erectile function and enabling couples to communicate about
      sexual problems were the most important factors to increase efficacy of ICI
      treatment.

PMID- 9647944
TI  - Engineering analysis of penile hemodynamic and structural-dynamic relationships:
      Part III--Clinical considerations of penile hemodynamic and rigidity erectile
      responses.
AB  - PURPOSE: The extent to which hemodynamic erectile responses predict penile
      buckling forces has not previously been analytically investigated. An engineering
      study was performed to compare hemodynamic data with penile buckling force
      values. METHODS: Dynamic infusion pharmacocavernosometry studies in 21 impotent
      patients (age 43, range 24-62 y) were accomplished to obtain information during
      penile erection concerning hemodynamic values, penile buckling forces and their
      determinants: intracavernosal pressure, erectile tissue mechanical properties and
      penile geometry. RESULTS: In the 21 patients, discrepancies existed in several
      patients who demonstrated normal hemodynamic values (low flow-to-maintain and
      high equilibrium intracavernosal pressures) but elevated cavernosal compliance
      values and diminished penile buckling forces. There was poor correlation between
      cavernosal compliance and equilibrium intracavernosal pressure (r = -0.36);
      better correlation between compliance and expandability (r = -0.72) and best
      correlation between dimensionless compliance and the dimensionless product of
      expandability with equilibrium pressure (r = -0.88). These data implied that
      cavernosal compliance was dependent on multiple factors, not only equilibrium
      intracavernosal pressure. CONCLUSIONS: Hemodynamic indices which correlate with
      intracavernosal pressure alone do not predict penile buckling forces since the
      latter are dependent not only on intracavernosal pressure but also on penile
      geometry and erectile tissue properties. The most relevant tissue property in
      predicting adequate penile buckling forces is cavernosal expandability. A new
      impotence classification system and diagnostic algorithm based on the
      determinants of penile rigidity and not exclusively on hemodynamic responses in
      proposed.

PMID- 9647945
TI  - Malignant priapism as the initial clinical manifestation of metastatic renal cell
      carcinoma with invasion of both corpora cavernosum and spongiosum.

PMID- 9647946
TI  - 'Treatment mills' under the Federal Trade Commission Act.
AB  - This paper is based on a presentation made by the author at the meeting of the
      American Urological Association's Society for the Study of Impotence on April 12,
      1997. The author addresses the general applicability of the Federal Trade
      Commission Act to advertising by so-called impotence 'treatment mills,' focusing
      in particular on the Federal Trade Commission's case in the matter of Genetus
      Alexandria, Inc. et al.

PMID- 9647947
TI  - The application of gene therapy to the treatment of erectile dysfunction.

PMID- 9647948
TI  - Is there a role of hypoxemia in penile fibrosis: a viewpoint presented to the
      Society for the Study of Impotence.
AB  - During erection, oxygen tension changes in the corpus cavernosum penis from 25-40
      mm Hg in the flaccid state to 90-100 mm Hg in the erect state. The relationship
      between corpus cavernosum trabecular structure and erectile function is dependent
      on a critical balance of smooth muscle to connective tissue for successful veno
      occlusion. In this article, the potential role for transforming growth factor
      beta(1) (TGF-beta(1)) and prostaglandin E (PGE) in maintaining a functional
      smooth muscle/connective tissue balance are discussed as well as the importance
      of oxygen tension in the synthesis of these factors. Correlations between animal
      models of disease as well as clinical reports are presented in support of a role
      for hypoxemia in penile fibrosis. A case is presented for a biological basis of
      nocturnal penile tumescence in the preservation of potency and an overall
      hypothesis for the molecular pathology of erectile dysfunction is proposed.

PMID- 9647949
TI  - Symposium on Peyronie's disease April 12, 1997.

PMID- 9647950
TI  - Advances in the medical therapy of Peyronie's disease: a brief review.

PMID- 9647951
TI  - Penile prosthesis implantation in the treatment of Peyronie's disease.
AB  - PURPOSE: This study was undertaken to evaluate the results and complications of
      penile prosthesis implantation in patients with erectile dysfunction caused by
      Peyronie's disease. MATERIALS AND METHODS: Men undergoing surgical intervention
      for erectile dysfunction caused by Peyronie's disease at the University of North
      Carolina School of Medicine were reviewed. Patients included 30 men aged 29-64
      (mean = 49.6) with a duration of Peyronie's disease from 12-72 months (mean =
      31.4 months). All men had palpable Peyronie's plague, significant penile
      curvature and plaque formation. All patients underwent implantation of AMS 700CX
      penile prostheses from 1993 to 1997. RESULTS: Penile straightening was carried
      out using modeling in 28 (93%) while plaque incision was necessary in 2 men (7%).
      All patients had a resultant straight penis with functional penile implant. There
      were no patients who suffered penile prosthesis infection and no mechanical
      malfunctions were observed during the follow-up. CONCLUSIONS: Penile prosthesis
      implantation with modeling is a safe, simple, effective technique for
      straightening penile curvature in patients undergoing implantation of penile
      prosthesis for Peyronie's disease. Penile prosthesis implantation is a safe,
      effective, low morbidity method for restoring potency in men with male erectile
      dysfunction and Peyronie's disease.

PMID- 9647952
TI  - Correction of penile curvature and Peyronie's disease: why I prefer the Nesbit
      technique.
AB  - In Peyronie's disease I found that the complication rate after plaque excision
      and dermal grafting to be high and started to use the Nesbit technique for the
      correction of penile deformity. Since 1977, the overall results have been
      satisfactory in 82% of 359 patients. The results improved when those patients
      with an impaired erection were assessed by colour doppler studies and a penile
      prosthesis implanted in those with a vasculogenic deficit. Post operative
      complications of the Nesbit technique are few and penile shortening was not a
      problem.

PMID- 9647953
TI  - Symposium on Peyronie's disease Society of Impotence Research meeting at the 1997
      American Urological Association meeting.

PMID- 9647954
TI  - Clinical trials and human sexuality: basic concepts and problems.
AB  - In considering the evaluation of pharmacological agents in the treatment of
      sexual dysfunction, four fundamental issues are discussed in this paper: (1) most
      pharmacological agents which have been used for this purpose act on
      neurotransmitter systems which are not specific to sexual response; (2) even when
      a sexually relevant pharmacological effect can be assumed, its effect on sexual
      behavior will be modulated by information processing; (3) the first attempts to
      evaluate the agent should focus on direct effects on the individual receiving the
      drug; and (4) evaluation of the relevance of the direct pharmacological effect on
      the well-being of a sexual relationship requires control of the considerable
      variance which exists in the capacity for change in sexual relationships.

PMID- 9647955
TI  - Clinical trials in sexual dysfunction.

PMID- 9647956
TI  - Psychological assessment measures of human sexual functioning in clinical trials.
AB  - This current review is intended to provide a brief overview of the major design
      and psychometric issues inherent in the development of psychological instruments
      to assess human sexual functioning. Particular emphasis has been placed on those
      issues which derive from the implementation of psychological tests as outcomes
      measures in clinical trials. Cardinal psychometric parameters are identified and
      reviewed, as are supplementary measurement criteria. Five specific psychological
      instruments are recommended and discussed, and each instrument's design
      characteristics, psychometric evaluation, and program of validation is briefly
      reviewed and evaluated.

PMID- 9647957
TI  - Quality of life assessment in sexual dysfunction trials.
AB  - Quality of Life (QOL) is an important outcome dimension in clinical trials of
      sexual dysfunction. This brief paper reviews the rationale for inclusion of QOL
      measures in clinical trials and considers the use of broad-based or generic
      measures of QOL, compared to disease-specific measures. Two disease-specific
      measures of QOL associated with erectile dysfunction are presented in detail.
      Each of these measures has certain advantages, although neither has been
      sufficiently validated to warrant large-scale use in clinical trials. Further
      research is needed, particularly on the impact of sexual dysfunction on QOL in
      women.

PMID- 9647958
TI  - Axial penile rigidity: determinants and relation to hemodynamic parameters.
AB  - Erectile dysfunction may be defined in terms of axial penile rigidity, the
      physical property that enables the erection to be utilized as a penetration tool
      during sexual activity. Erectile dysfunction occurs when inadequate axial penile
      rigidity results in buckling of the penile column when subjected to axial
      compressive loading situations during vaginal intromission. New multi
      disciplinary engineering studies of penile hemodynamic and structural dynamic
      relationships are reviewed concerning the determinants of axial penile rigidity.
      Axial penile rigidity develops as a continuum during the increases in
      intracavernosal pressure and volume changes from the flaccid state and is
      influenced by intracavernosal pressure, penile tissue mechanical properties and
      penile geometry. Two penile tissue mechanical properties are especially relevant;
      cavernosal maximum volume at relatively low intracavernosal pressure, and tunical
      distensibility, the relative volume of the fully erect to completely flaccid
      pendulous penis. Two penile geometric properties are critical; the penile aspect
      ratio, defined as the diameter to length ratio of the pendulous penis, and the
      magnitude of the flaccid penile diameter. Clinically measured values of axial
      buckling forces in patients undergoing dynamic pharmacocavernosometry strongly
      correlated to theoretic-based analytic derived magnitudes of axial penile
      rigidity based on these above pressure, tissue and geometric determinants. Since
      axial penile rigidity is not exclusively dependent upon intracavernosal pressure,
      patients with normal erectile hemodynamics may be erroneously labelled as having
      psychogenic dysfunction where their true pathophysiology may be related to
      abnormal penile tissue properties and/or penile geometric factors. Similarly,
      some patients may claim sufficient rigidity for penetration, but have abnormal
      hemodynamic erectile function studies. They may have uniquely advantageous tissue
      mechanical and/or geometric properties. More research is needed concerning axial
      penile rigidity, a most influential factor determining functional erectile
      quality, erectile potency and successful coitus.

PMID- 9647959
TI  - Neural and pharmacological determinants of erection.
AB  - An integrative analysis of the determinants of erection will reveal that almost
      all the common actions of smooth muscle and endothelial cells found in normal
      vascular biology (NVB), and some neural mechanisms, have roles in supporting
      erectile function. Many of these cellular mechanisms have been harnessed to
      create drugs that are or will be used to treat erectile dysfunction. Without
      standard diagnostic or therapeutic methods, or classifications, it is difficult
      to compare drugs, and difficult to target the specific deficiencies causing
      erectile dysfunction. A classification is suggested here that hinges on the
      identification of two main characteristics. Firstly, there is a fundamental
      difference between initiating an erection (initiators) and facilitating or
      enhancing an erection already initiated by other processes (conditioners), and
      secondly, there are different implications for adverse effects and drug delivery
      that arise from targeting central nervous system or peripheral systemic
      processes. These properties suggest a classification of treatments based on a two
      by-two matrix. Within each class drugs will be more equivalent enabling better
      comparisons and more standardized evaluative strategies. By observing the
      characteristics of patients benefiting from drugs of an identified class it may
      be possible to develop a physiologically based classification of diagnoses. There
      may be logical combinations of drugs that will be assembled in clinical practice,
      taking suitable agents from one of two or more classes. No single mechanism will
      stand out as overwhelming and no single drug will treat all erectile dysfunction.

PMID- 9647960
TI  - Central control and inhibitory mechanisms in male sexual response.
AB  - At this present time there is a serious gap in our understanding of how
      psychological difficulties result in specific sexual dysfunction. In this paper,
      a theoretical model of sexual response is proposed which involves the parallel
      existence of excitatory and inhibitory mechanisms in the central nervous system.
      Evidence for both specifically sexual and non-specific inhibitory mechanisms are
      discussed; at this stage either or both may be relevant to the model. It is
      postulated that the propensity for neurophysiological inhibition of sexual
      response varies across individuals; in the majority of cases it is assumed that
      this mechanism has adaptive value. However, in those individuals for whom the
      propensity is lacking, high risk sexual behavior may be more likely. In contrast,
      those individuals with high propensity for central inhibition may be more
      vulnerable to sexual dysfunction. If valid, this model opens a new research
      agenda for both male sexual dysfunction and high risk sexual behavior.

PMID- 9647961
TI  - A psychophysiological approach to assessing premature ejaculation.
AB  - A hierarchical psychophysiological model is described that provides a working
      framework for clinicians interested in addressing issues related to premature
      ejaculation (PE). Within this framework, psychophysiological laboratory analysis,
      used in conjunction with conventional self-report measures, has potential to
      contribute both to the measurement and understanding of premature ejaculation and
      to the assessment of treatment procedures aimed at alleviating PE.

PMID- 9647962
TI  - Definitions and classification of male sexual dysfunction.
AB  - The definitions and classifications of male sexual dysfunction as described by
      the diagnostic and statistical manual of the American Psychiatric Association are
      reviewed. The absence of clear operational criteria for these diagnoses and the
      varying definitions used by current investigators are highlighted.

PMID- 9647963
TI  - Sexual function assessment in the male: physiological and self-report measures.
AB  - Sexual arousal in the male involves a complex interaction of physiological and
      subjective processes. In recent years, a number of physiological and self-report
      methods have been described for assessing sexual function in healthy and
      dysfunctional males. Physiological methods include the Rigiscan, volumetric and
      circumferential plethysmography, and the erectiometer. Despite their widespread
      use, each of these approaches has significant limitations in assessing male
      sexual function. Recent self-report measures include the International Index of
      Erectile Function (IIEF), Brief Male Sexual Function Inventory (BMSFI), and
      Center for Marital and Sexual Health Questionnaire (CMSH-SFQ). A structured
      interview for sexual function assessment has also been described (Derogatis
      Interview for Sexual Functioning--DISF-SR), in addition to daily diary and event
      log methods. The relative strengths and weaknesses of each of these approaches
      are reviewed.

PMID- 9647964
TI  - Evidence based assessment of erectile dysfunction.
AB  - Do we need impotence testing? Yes, it is the clinician's obligation to establish
      the etiology of impotence: end organ vascular failure vs neurologic dysfunction
      vs psychosexual dysfunction, classify the severity of that dysfunction, and
      select a therapy that is not only acceptable to the patient but also addresses
      his pathology. The most commonly utilized diagnostic tests for erectile
      dysfunction are outlined in this monograph. Nocturnal erections are evaluated by
      tests commonly known as nocturnal penile tumescence (NPT) studies. NPT has been
      measured by each of the following methods: stamp test, Snap Gauges, strain
      gauges, NPTR (Rigiscan, Osbon Medical Systems), and sleep lab NPTR. Normal
      Nocturnal Penile Tumescence and Rigidity (NPTR) depends on both the integrity of
      the corticospinal efferents to the penis and vascular responsiveness of the
      penile tissues to those nerve signals. When nocturnal erections are of
      appropriate duration and strength the central and peripheral neuroeffectors and
      intra-corporal regulators of penile hemodynamics are intact. Unfortunately,
      abnormal NPTR is of little value in determining the etiology or classifying the
      severity of vascular impotence; the most prevalent kind of end organ failure. The
      sacral reflex arc of erection consists of somatosensory afferents via the dorsal
      and pudendal nerves and autonomic efferents via the pelvic and cavernous nerves.
      These afferents have been measured indirectly by somatosensory evoked potentials
      (SSEP) and bulbocavernosus reflex latency (BCR). Penile EMG's have recently been
      recorded, corporal cavernosal smooth muscle electrical activity: CC-EMG. This
      technology is far from standardized; computer-assisted interpretations of penile
      electrical potentials may eventually differentiate afferent nerve pathologies so
      long inferred in: diabetes, spinal cord injury and following radical pelvic
      surgery. Numerous diagnostic tests have been employed to evaluate penile
      hemodynamics: penile plethysmography, penile blood pressures, penile brachial
      index, selective internal pudendal pharmacoangiography, Doppler sonography,
      dynamic infusion cavernosometry/cavernosography, nuclear washout radiography, and
      color duplex Doppler ultrasound. Insufficient corporal veno-occlusion is
      implicated in up to 50% of patients. The diagnosis and demonstration of venous
      leakage requires complete smooth muscle relaxation. Veno-occlusive dysfunction is
      associated with poorly sustained erections; this pathology has traditionally been
      evaluated with Dynamic Infusion Cavernosometry and Cavernosography. DICC is an
      invasive test, and is now primarily reserved for patients considering the option
      of vascular reconstructive procedure. Pharmacotesting consists of intracavernous
      injection and visual rating of the subsequent erection; the test is the most
      commonly used office procedure for diagnosing erectile dysfunction. It is simple,
      minimally invasive, and performed without monitoring equipment. Hemodynamic
      investigations suggest that a positive injection test is associated with normal
      veno-occlusion, but not necessarily with normal arterial function. When the
      penile response to pharmacotesting is suboptimal or equivocal, diagnostic testing
      with duplex Doppler assessment should be performed. The penile blood flow study
      (PBFS) provides an objective, minimally invasive evaluation of a
      suboptimal/equivocal erectile response.

PMID- 9647965
TI  - Evidence based assessment of rapid ejaculation.
AB  - This manuscript reviews the clinical and scientific methods utilized to assess
      treatment outcome in rapid ejaculation. The current methods and measures are
      critically evaluated and suggestions for future research efforts are included.

PMID- 9647966
TI  - The role of androgens and the menopause in the female sexual response.
AB  - There is increasing awareness that many women experience symptoms of androgen
      deficiency after either natural or surgical menopause. The predominant complaint
      of affected women is less sexual desire. Many women experiencing the clinical
      symptoms of androgen deficiency and low free testosterone levels respond well to
      testosterone replacement therapy. However, some women also have additional psycho
      social issues complicating their symptomatology and these must be addressed
      either before or concurrently with androgen replacement.

PMID- 9647967
TI  - Vasculogenic female sexual dysfunction: vaginal engorgement and clitoral erectile
      insufficiency syndromes.
AB  - The first phase of the female sexual response, associated with neurotransmitter
      mediated vascular smooth muscle relaxation, results in increased vaginal
      lubrication, wall engorgement and luminal diameter as well as increased clitoral
      length and diameter. Specific physiologic impairments of vasculogenic female
      sexual dysfunction include vaginal engorgement and clitoral erectile
      insufficiency syndromes. These syndromes exist when during sexual stimulation
      abnormal arterial circulation into the vagina or clitoris, usually from
      atherosclerotic vascular disease, interferes with normal vascular physiologic
      processes. Clinical symptoms may include delayed vaginal engorgement, diminished
      vaginal lubrication, pain or discomfort with intercourse, diminished vaginal
      sensation, diminished vaginal orgasm, diminished clitoral sensation or diminished
      clitoral orgasm. An animal model of this syndrome, with significant physiologic
      responses between the control and the atherosclerotic pelvic nerve stimulated
      hemodynamic responses, is discussed. Non-atherosclerotic, traumatic vascular
      disease of the ilio-hypogastric-pudendal arterial bed from pelvic fractures or
      blunt perineal trauma may also result in diminished vaginal/clitoral arterial
      blood flow following sexual stimulation. Diagnostic studies assessing the
      hemodynamic integrity of the ilio-hypogastric-pudendal arterial bed to the vagina
      and clitoris and new oral/topical pharmacologic strategies for enhancing
      vaginal/clitoral blood flow in patients with vasculogenic female sexual
      dysfunction are discussed. There is a growing body of evidence that women with
      sexual dysfunction will commonly have physiologic abnormalities, such as
      vasculogenic female sexual dysfunction, contributing to their overall sexual
      health problems.

PMID- 9647969
TI  - Psychophysiological models of female sexual response.
AB  - Psychophysiology provides a methodology and a model for evaluating physiological
      and psychological (cognitive-affective) components of sexuality in a relatively
      controlled laboratory setting. Laboratory responses can then be correlated with
      key sexual or nonsexual self-reported behaviors, thoughts and feelings occurring
      in the person's daily environment. Given the fact that human sexual response is
      the result of a complex interaction of psychosocial and physiological factors, a
      psychophysiological model provides one valuable inroad to exploring and analyzing
      sexual response patterns. The following comments briefly evaluate the current
      status of the use of this model as it applies to female sexual response.

PMID- 9647968
TI  - Ovarian hormones and vaginal blood flow: using laser Doppler velocimetry to
      measure effects in a clinical trial of post-menopausal women.
AB  - OBJECTIVES: To describe the use of laser Doppler velocimetry for measurement of
      vaginal blood flow and report the effects of estrogen compared with estrogen
      androgen treatment in post-menopausal women. DESIGN: Literature review of pelvic
      blood flow studies and sexual function. Findings from a prospective, randomized,
      parallel study. SETTING: Normal human volunteers in an academic research
      environment. INTERVENTIONS: Laser Doppler measurements of vaginal blood flow were
      compared before and after the administration of oral esterified estrogens or
      esterified estrogens plus methyltestosterone for four and eight weeks of daily
      drug administration. MAIN OUTCOME MEASURES: Vaginal blood flow velocities.
      RESULTS: Laser Doppler velocimetry proved readily adaptable for measurement of
      vaginal blood flow. Although esterified estrogens plus methyltestosterone showed
      greater effects on blood flow than esterified estrogens alone, the results were
      not statistically significant. CONCLUSIONS: Vaginal blood flow is an objective
      measure of sexual function which can be determined with laser Doppler
      velocimetry. The vasodilator effects of esterified estrogens and esterified
      estrogens with methyltestosterone are similar.

PMID- 9647970
TI  - Definition and classification of female sexual disorders.
AB  - The diagnosis and classification of female sexual disorders has undergone
      significant changes over the last fifty years as a function of changing societal
      expectations for female sexual conduct, available knowledge about sexual
      psychophysiology and actual clinical practice. Currently, female sexual disorders
      are conceptualized as disturbances in desire, arousal, or orgasm as well as
      sexual pain disorders which include dyspareunia and vaginismus. The lack of
      objective, empirically-grounded criteria for diagnosis as well as the comorbidity
      of female sexual disorders contributes to the lack of reliability in the
      diagnosis of female sexual complaints. At the present time, hypoactive sexual
      desire disorder is the most commonly diagnosed female sexual disorder followed by
      female orgasmic disorder. Nevertheless, the major clinical complaints among women
      center on their dissatisfaction with such non-genital behaviors as affection,
      communication, and non-genital touching as well as issues of attraction and
      passion. These factors should be assessed as well as genital response for greater
      validity in evaluating female sexual disorders in both research and clinical
      practice.

PMID- 9647971
TI  - Physiological measures of vaginal vasocongestion.
AB  - This paper reviews reliability, specificity, and practical applicability of the
      two most promising and widely used methods for measuring blood flow within the
      vagina: the oxygenation-temperature method and vaginal photoplethysmography. It
      was concluded that the oxygenation-temperature method and vaginal pulse amplitude
      as measured by the photoplethysmograph are both specific indicators of
      physiological sexual arousal. Although vaginal pulse amplitude seems to be the
      method of choice for measuring vaginal vasocongestion up to orgasm, and the
      oxygenation-temperature method for measuring orgasm, these measures should not be
      used in isolation. It is argued that women's sexual function should be evaluated
      using vaginal vasocongestion measures in conjunction with subjective indices.
      Finally, the field is in need of studies comparing physiological and subjective
      sexual responses in clinical and non-clinical groups.

PMID- 9647972
TI  - Psychological assessment measures of female sexual functioning in clinical
      trials.
AB  - The focus of this review is on the psychological measurement of female sexual
      functioning, and the particular requirements associated with the implementation
      of psychological instruments as outcomes measures in clinical trials. In addition
      to the general psychometric criteria which must be met by all psychological
      measures, unique confounds associated with the nosology of female sexual
      dysfunctions are also discussed. A rationale for the utilization of measurement
      models closely tied to the sexual response cycle is articulated, and five
      specific test instruments which reflect this rationale to varying degrees are
      reviewed as to their psychometric characteristics, and validity as potential
      outcomes measures in clinical trials.

PMID- 9647973
TI  - The clinical evaluation of dyspareunia.
AB  - Strictly defined, dyspareunia means 'pain with intercourse'. The psychiatric DSM
      IV subdivides and expands this definition and introduces psychogenic factors into
      the differential diagnosis. This allows development of a biogenic-psychogenic
      model, whereby organic or psychological factors can be present separately or in
      combination, within the disorder. Sexual dysfunctions are estimated to be present
      in 19-63% of women, with dyspareunia the primary complaint in 8-48%. The clinical
      evaluation of dyspareunia should include a thorough history and meticulous
      gynecologic examination. Laboratory or imaging studies should be ordered as
      warranted by suggestive history or exam findings. Identified causes should be
      treated and counseling considered. Three clinical dilemmas remain. Firstly, lack
      of standardization of exam findings; secondly discrepancy between objective
      physical findings and subjective patient complaints; and thirdly paucity of
      therapeutic options for patients, especially those with an unclear diagnosis. An
      integrated psychogenic-biogenic model should be developed and implemented for
      effective diagnosis and treatment of dyspareunia.

PMID- 9647974
TI  - Issues and priorities in the development of drug treatments for female sexual
      dysfunction.

PMID- 9647975
TI  - Sexual functioning in the spinal cord injured.
AB  - This article reviews current knowledge about the impact of SCI on male and female
      sexual responses including erectile function, lubrication ejaculation and orgasm.
      The ability to achieve erection, lubrication and ejaculation can be described
      based upon the degree and type of neurologic injury affecting the sacral spinal
      segments. The ability of SCI individuals to achieve orgasm has not been found to
      be based upon the type of degree of neurologic injury. The implications of these
      findings to increase our understanding of human sexual neurophysiology is also
      discussed.

PMID- 9647976
TI  - Psychiatric illness and sexual function.
AB  - Impaired sexual function has been noted to occur in various psychiatric
      illnesses. In affective disorders, disturbances of libido, erection and orgasm
      have been reported. Disordered sexual behavior has also been noted in patients
      with schizophrenia and anorexia nervosa. Clinical speculation suggests that
      anxiety disorders may also be associated with a higher prevalence of sexual
      problems.

PMID- 9647977
TI  - Ethical and cultural concerns in sexual function assessment.
AB  - The ethical and cultural issues accompanying sex research methods are rarely
      discussed. The present remarks briefly examine three previously described ethical
      principles--respect for people, beneficence and justice--as they might relate to
      sexual dysfunction assessment in clinical trials. Given the fact that sexuality
      is a social behavior and the outcome measures are reliant on some form of self
      report, there are specific pressures on investigators to conduct research
      assessment that respects ethical principles and cultural values. Examples with
      respect to screening criteria and participant selection are discussed.
      Recommendations include: (a) excluding participants with selected sexual and non
      sexual diagnoses, psychosocial behaviors and habits; (b) including proportional
      ethnic groups as well as non-heterosexual participants; and (c) considering the
      couple, rather than just an individual, as study subjects who each require
      medical and psychosocial screening, assessment, and informed consent.

PMID- 9647978
TI  - [Acute liver failure].

PMID- 9647979
TI  - [Acute pancreatitis after shock, ischemia, reperfusion, trauma and infection].

PMID- 9647980
TI  - [Acute heart failure].

PMID- 9647981
TI  - [Acute septic cardiomyopathy].

PMID- 9647982
TI  - [Disordered hemostasis related to sepsis and SIRS].

PMID- 9647983
TI  - [Acute encephalopathy, polyneuropathy and myopathy in the critically ill
      patient].

PMID- 9647984
TI  - [Multiple organ dysfunction syndrome and multiple organ failure. Diagnosis,
      prognosis and therapeutic concepts].

PMID- 9647985
TI  - [Scores for multiple organ dysfunction and multiple organ failure].

PMID- 9647986
TI  - [Colorectal carcinoma. Prevention and early detection].

PMID- 9647987
TI  - [Current therapy of coronary heart disease. Conservative measures].

PMID- 9647990
TI  - [Translaryngeal intubation in long-term ventilation].

PMID- 9647992
TI  - [Ulcerating skin lesions in terminal renal failure. Successful therapy with
      carbon perfusion].

PMID- 9647993
TI  - [18-year-old patient with left thoracic pain].

PMID- 9647994
TI  - [Acidic blood pH value caused by stress?].

PMID- 9647995
TI  - [Dexamethasone in treatment of brain edema and intracranial hemorrhage].

PMID- 9647996
TI  - [Iron replacement. Oral or parenteral?].

PMID- 9647997
TI  - [APC resistance. Significance--diagnosis--therapeutic consequences].

PMID- 9647998
TI  - [Managing advance directives in emergency care].

PMID- 9647999
TI  - [Interactions between anticoagulants and cardiovascular drugs].

PMID- 9648000
TI  - [6th Munchen AIDS-Days. Azithromycin in HIV-associated opportunistic infections].

PMID- 9648001
TI  - [From prevention to therapy of thromboembolic processes: low-molecular heparin in
      body-weight adapted dosages].

PMID- 9648002
TI  - [Twin transfusion syndrome].

PMID- 9648003
TI  - [Role of cervical modifications in threatened premature labor].
AB  - Uterine cervical modifications play a central role in preterm labor and are one
      of the main indicators for the clinical diagnosis of this syndrome. Modifications
      of the cervix are either isolated events "cervical incompetence" or associated
      with cervicovaginal infection, which is an important etiological factor.
      Furthermore, the extent of cervical modifications in preterm labor is probably
      related to the prognosis of preterm delivery. Certain developments in the
      treatment of preterm pregnancy have focused on the uterine cervix (e.g. cervical
      cerclage, treatment of cervicovaginal infections) and such strategies may
      facilitate the prevention of preterm delivery. The information currently
      available emphasizes an independent role for the uterine cervix in preterm labor.
      As a consequence, it should be realised that even though there is a direct
      association between cervical modifications and uterine contractions, management
      of preterm labour must not be directed exclusively at the control of uterine
      contractions and tocolysis.

PMID- 9648004
TI  - [Perinatal hemolytic disease. Part 2: Prevention and management].
AB  - There has been a dramatic reduction in the incidence of neonatal mortality due to
      fetal hemolytic disease since the introduction of Rhesus prophylaxis. Although
      routinely used since 1968, the exact mode of action of anti-D IgGs is still not
      fully understood. Notable advances have taken place in the screening and the
      management of fetal hemolytic disease. This article describes the antibody
      detection in the mother, and the fetal management with ultrasound amniocentesis,
      fetal blood sampling and intrauterine transfusions. Finally, the postnatal
      management is also considered.

PMID- 9648005
TI  - [Female fertility prognosis and diethylstilbestrol. Personal data and review of
      the literature].
AB  - Diethylstilbestrol (DES) exposure in utero in females is a cause of clear-cell
      adenocarcinoma of the cervix and of several anatomical and functional disorders
      of the genital tract. DES exposure must be evoked whenever counselling women for
      reproductive disorders. In France around 80,000 women have had in utero DES
      exposure. The cases of 4 young women who consulted our Reproduction Center for
      reproductive disorders illustrate the usual difficulties faced by these patients.
      In spite of their difficult past reproductive history (uterine malformations,
      repeated miscarriages, ectopic pregnancies) and low fertility rate, all four
      women conceived successfully, either after spontaneous or induced ovulation. We
      stress the need for adapted psychological and medical care which can lead to
      successful childbearing in the vast majority of these high-risk patients.

PMID- 9648006
TI  - [Monitoring women on tamoxifen ].
AB  - Worldwide, 7 million women are taking tamoxifen for breast cancer. The beneficial
      effects of tamoxifen on patient survival have been clearly demonstrated.
      Tamoxifen has few adverse effects and severe complications are very uncommon. An
      higher risk of endometrial cancer at the 20 mg/d dosage has been discussed and if
      it does exist, is minimal (RR x 2 instead of 1.3). Patient monitoring is
      basically clinical with an annual examination of the lower limbs and genital
      organs and an ophthalmological examination. Further explorations are needed in
      cases with specific symptoms, especially metrorrhage. There has been no proof
      that systematic endometrial cytology or ultrasound explorations are useful.

PMID- 9648007
TI  - [Ultrasonographic signs of chromosome aberrations].
AB  - We reviewed the literature on ultrasonographic criteria allowing prenatal
      diagnosis of chromosome aberrations, especially the most frequent: trisomy. Signs
      vary depending on the term of the ultrasound examination (first trimester
      ultrasound is often performed to early and several signs are observed in the
      second trimester). During the first trimester, the main criteria is the diagnosis
      of nuchal clearness 3 mm. The distance can only be measured with an appropriate
      sagittal CRL section by an experienced operator. The ideal term of this
      morphology ultrasound is 10 weeks gestation. During the second trimester, there
      are many suggestive criteria including non-specific signs: anomalous quantity of
      amniotic fluid, short femur, nuchal thickness 6 mm, isolated anomaly of the
      umbilical velocimetry, pyelectasy and fetal malformations (mainly cerebral or
      abdominal, including ophalocele and diaphragmatic hernia, anomalies, abnormal
      heart anatomy, cystic hygroma, facial anomalies and malformations of the members,
      often abnormal flexion of the hands).

PMID- 9648008
TI  - [Twenty practical questions about prenatal corticosteroid therapy].
AB  - Since Liggins and Howie first published their work, numerous studies have shown
      that corticosteroids significantly decrease perinatal mortality and morbidity,
      without complication for the mothers and child. Corticosteroids should be
      prescribed in case of threatening premature birth. Imminent delivery premature
      rupture of the membranes and gestationnal age over 34 weeks are not
      contraindications to prescription, as corticosteroids can be safely given all in
      these circumstances. Theoretically, more than half of premature neonates should
      have been treated with corticosteroids. Actually, only 20% or less are currently
      treated. The cost-effectiveness ratio of an antenatal corticosteroid policy would
      be extremely positive: more than 1,500 prenatal deaths could theoretically be
      avoided in France annually and the overall cost of neonatal care would decrease
      by 10%.

PMID- 9648009
TI  - [Urinary stress incontinence. Comparison of the Raz technique and the Bologna
      technique. Analysis of a series of 188 patients].
AB  - OBJECTIVE: Our purpose was to evaluate and compare the perioperative morbidity
      and the long-term results of the Raz colposuspension and the Bologna operation
      for the treatment of stress urinary incontinence in women. STUDY DESIGN: Data of
      188 women who underwent either a Bologna operation (group 1) or a Raz
      colposuspension (group 2) for the treatment of stress urinary incontinence
      between January 1, 1987 and December 1, 1995 were analysed retrospectively
      regarding history, preoperative evaluation, associated surgical procedures,
      complications and cure and failure rate. POPULATION AND METHODS: 80 patients were
      treated with the Bologna operation and 108 with the Raz colposuspension. Patients
      with prior anti-incontinence surgery, and patients with a preoperative diagnosis
      of urge incontinence were excluded from the study. Success was defined both
      subjectively (complete absence of complaint of stress urinary incontinence) and
      objectively (no evidence of loss of urine on cough provocation during physical
      examination). Survival curves were generated in each group for time to event
      data: "time to recurrent stress incontinence" and compared by the logrank test. A
      multivariate analysis using a Cox proportional hazards regression model was
      performed to indentify possible outcome predictors. RESULTS: The success rate of
      group 1 was significantly higher than that of group 2 (p = 0.00001). The median
      of success was 51 months in group 1 and 21 months in group 2 (p = 0.00001). The
      incidence of intraoperative complications in each group (inadvertent cystostomy,
      hemorrhage) did not differ. The multivariate analyses using the Cox regression
      model showed that the most highly correlated variable with the surgical cure rate
      was the type of surgical anti-incontinence procedure adopted: Bologna or Raz (p =
      0.00001) CONCLUSION: In our hands, the Bologna operation has a higher cure rate
      than the Raz colposuspension. For us, when treating patients with stress urinary
      incontinence by the vaginal route, the Bologna operation is indicated when
      sufficient anterior vaginal tissue is available to create vaginal bands.

PMID- 9648010
TI  - [Prevention of prematurity in 842 consecutive twin pregnancies].
AB  - OBJECTIVE: To evaluate the effects of a specific management in prevention of
      prematurity in twin pregnancies. METHOD: The parameters involved in obstetrical
      follow-up of twin pregnancies were evaluated in a retrospective study of 842 twin
      pregnancies between 1979-1992. RESULTS: Five-hundred-and-fifteen pregnancies were
      spontaneous. Two-hundred followed treatment with ovulation induction agents and
      127 were due to in vitro fertilization. Early diagnosis of twin pregnancies
      allowed preventive measures against prematurity. Management of twin pregnancies
      included rest at home and regular clinical examination of the cervix. Monthly
      consultations and monthly ultrasounds were performed at hospital. Weekly
      consultations were made by midwives at home. Hospitalization was not systematic,
      but was necessary in cases of maternal complications. The diagnosis of twin
      pregnancy was made before 16 weeks in 82.4% of the cases. The mean gestational
      age at delivery was 36.2 weeks. The prematurity rate was 45.96%. The mean weight
      of the neonates was 2,376 +/- 533 g for the first twin and 2,297 +/- 547 g for
      the second twin. The mean Apgar score at 5 minutes was 9.7 and 9.3, respectively
      for the first and the second twin. The perinatal mortality was 39.3 per 1,000.
      The main neonatal complications resulted from prematurity. Twins were
      hospitalized in the intensive care unit in 20.7 cases. CONCLUSION: The present
      study supports early diagnosis of multiple pregnancies with systematic ultrasound
      at 11-13 weeks for each pregnancy, information of the patients, rest at home and
      regular clinical examination of the cervix.

PMID- 9648011
TI  - [Intracystic breast carcinoma. A case report].
AB  - Intracystic breast carcinoma is a malignant which develops within breast ducts.
      The clinical examination reveals a breast cyst containing a blood fluid which
      persists after the puncture. Fine-needle aspiration cytology may be benign. The
      endocystic mass is detected well by the ultrasound and US-guided puncture is
      possible. Papillary carcinoma is the most frequent histological type.
      Conservative prophylactic radiotherapy with surgery can be proposed. Prognosis is
      poorer with stromal involvement.

PMID- 9648012
TI  - [Ureteral suture by laparoscopy: a new case. Review of the literature].
AB  - A wound to the ureter is a possible complication of laparoscopy and is usually
      repaired by suture requiring laparotomy. We report a case of a laparoscopic
      stitch and review the pertinent literature.

PMID- 9648013
TI  - [Prenatal diagnosis of a pancreatic cyst due to Ivemark II syndrome].
AB  - We present a case of pancreatic cyst associated with other malformations which
      was diagnosed at antenatal ultrasound. Renal, hepatic, and pancreatic dysplasia
      as described by Ivemark in 1959 was confirmed by the pathology examination. This
      uncommon and lethal syndrome demonstrates autosomic recessive transmission.
      Ultrasound evidence of renal, hepatic and pancreatic dysplasia, associated with
      femoral abnormalities is suggestive of Meckel's syndrome. Other differential
      diagnoses are more easily distinguished (chondrodysplasia, chromosomal or
      metabolic abnormalities).

PMID- 9648014
TI  - [Thoughts on a case of unrecognized congenital rubella].
AB  - We recently observed a case of congenital rubella which had gone unrecognized
      despite regular obstetrical care. This case emphasizes the importance of careful
      screening for rubella at diagnosis of pregnancy. Minute analysis of the initial
      maternal antibody levels is essential to rule out possible contamination during
      pregnancy. The problem of interpreting serodiagnostic data is discussed.

PMID- 9648015
TI  - [Need for information in obstetrical epidural analgesia].

PMID- 9648016
TI  - Is it only rock 'n' roll? The chicken-and-the-egg dilemma.

PMID- 9648017
TI  - Fine-needle aspiration of breast masses. A review of its role in diagnosis and
      management in adolescent patients.
AB  - PURPOSE: To assess the role of fine-needle aspiration biopsy (FNA) in the
      evaluation and management of breast masses in adolescents. METHODS: All FNAs
      performed on organ masses over a 15-year period on patients age 21 years and
      younger were evaluated. Cases were collected from four large university
      affiliated teaching hospitals and clinics. Pathology records from the laboratory
      information systems were reviewed. Data included clinical information, anatomic
      site, and cytologic diagnoses. Surgical follow-up was included when available.
      RESULTS: Three hundred and twenty-five FNAs from 302 patients were reviewed. Of
      325 aspirates, 59 were breast FNAs (in 51 patients: 4 males and 47 females).
      Among all organs, the breast was the most common one aspirated in females. Of the
      breast aspirates in females, 49% were diagnosed as fibroadenomas. No cases of
      malignant breast disease or phyllodes tumors were encountered. Surgical biopsy
      follow-up was available in 23.7% of the patients. Of those masses which were
      subsequently surgically biopsied, most were diagnosed as either fibroadenoma (11)
      or juvenile fibroadenoma (two). One other case biopsied showed ductal hyperplasia
      and adenosis. The majority of the remaining cases were followed up clinically,
      since the clinical nature and cytologic features of the lesions were those of
      fibrocystic changes or benign cysts. CONCLUSIONS: In the series of FNAs we
      examined, breast masses were the most frequent lesions aspirated in adolescent
      females, with fibroadenomas being the most common lesion encountered. FNA proved
      to be a useful and reliable tool in the evaluation and management of masses
      involving the adolescent breast. The majority of breast masses in adolescents are
      benign, and lesions can be managed conservatively in this age group. The use of
      noninvasive diagnostic procedures such as FNA and ultrasound can reduce the need
      for open surgery during breast development.

PMID- 9648018
TI  - Changes in self-esteem in black and white girls between the ages of 9 and 14
      years. The NHLBI Growth and Health Study.
AB  - PURPOSE: We examined changes in self-esteem and feelings of competence with
      physical appearance and social acceptance over approximately 5 years in 1166
      white and 1213 black girls, aged 9 and 10 years at baseline. METHODS: Maturation
      stage and body mass index (BMI) were assessed annually. Biennially girls
      completed Harter's Self-Perception Profile for children. Changes were analyzed in
      the context of race, sexual maturation, BMI, and household income. Longitudinal
      regression models were used to compare trends with age in global self-worth,
      physical appearance, and social acceptance. RESULTS: Mean global self-worth
      showed little change over ages 9-14 years in blacks (p = 0.09) but decreased in
      whites (p < 0.001). Mean physical appearance scores for both races declined
      between ages 9 and 14 years (blacks, p < 0.001; whites, p < 0.001). Mean social
      acceptance scores increased for both races between ages 9 and 14 years (blacks, p
      < 0.001; whites, p < 0.001). For all three scores, these changes differed between
      blacks and whites (all three p values, < or = 0.002). Adjustment for maturation
      stage, BMI, and household income did not alter the significance or direction of
      racial differences in the changes with age in global self-worth and physical
      appearance scores. Self-worth, physical appearance, and social acceptance scores
      decreased with increasing BMI. Decreases in physical appearance and social
      acceptance scores with increasing BMI were smaller in blacks than in whites (p <
      0.05). After adjustment for maturation stage and household income, racial
      differences in social acceptance scores depended on BMI (p < 0.05) but not on age
      (p = 0.008). CONCLUSIONS: This article reports the first data on self-esteem
      scores by age for a large population of black girls aged 9 and 14 years and
      concludes that self-esteem does not follow the same developmental pattern in
      black as in white girls. A reason for black girls' higher and more stable self
      worth and their greater satisfaction with their physical appearance compared to
      white girls may be racial differences in attitudes toward physical appearance and
      obesity.

PMID- 9648019
TI  - Self-reported honesty among middle and high school students responding to a
      sexual behavior questionnaire.
AB  - PURPOSE: To determine self-reported honesty in completing a sexual and other risk
      behavior questionnaire among middle and high school students, and to relate
      honesty scores to sexual behavior item responses as a method to detect bias in
      reporting. METHODS: A self-administered questionnaire measuring overall honesty
      (7-point rating scale), sexual honesty (5-category scale), and selected sex
      behaviors was used. Urban, predominantly minority middle and high schools (Grades
      7-12) were examined, and participants were 3144 male and female students in
      middle (mean age = 13.7 +/- 2.0) and high (17.3 +/- 1.6) school health classes.
      RESULTS: The majority of students stated that they had been very or completely
      honest in responding to items on the questionnaire. Seventy-eight percent of
      middle school males (lowest rate), and 94% of high school females (highest rate)
      reported honesty. Middle school males were most likely to declare dishonesty
      regarding sexual behavior items, overstating their actual behavior (14%), while
      middle school girls were most likely to understate (8%) their behavior. Self
      reported sexual honesty and reports of behavior were most consistent for
      understaters. That is, those subjects who answered that their questionnaire
      responses underreported their true sexual behavior did, in fact, report lower
      sexual activity on selected survey items. CONCLUSION: Middle and late adolescents
      reported high levels of honesty in responding to a sexuality-related
      questionnaire. When interpreting such questionnaire data, correction for the
      tendency to overstate among middle school males and understate among middle
      school females should be considered; conclusions about self-reports of sexual
      behavior among young adolescents need to take into account degree of honesty.
      However, the presence of some overreported and some underreported behavior does
      not invalidate interpretation of the overall survey findings.

PMID- 9648020
TI  - The school-linked health center: a promising model of community-based care for
      adolescents.
AB  - PURPOSE: To examine the nature of the linkages between school-linked health
      centers (SLHCs) and schools; the centers' services, staffing, financing, and
      other operational details; and the advantages of this model of care. METHOD:
      Twenty-one SLHCs completed a written survey on a range of operational issues,
      including types of services provided, staffing patterns, budgets, and populations
      served in 1995. The researchers conducted on-site interviews with six centers and
      telephone interviews with 14 centers to obtain more detailed information.
      RESULTS: Although each SLHC has a unique program design, the study identified
      characteristics common to all sites. In general, SLHCs provide comprehensive
      medical, reproductive health, mental health, and health education services
      designed for adolescents. Staffed with a minimum of an administrator, a primary
      care provider, a nurse, and an administrative assistant, SLHCs serve students
      from more than one school as well as out-of-school youth. SLHCs develop formal
      and/or informal linkages with schools to improve outreach and follow-up services.
      CONCLUSIONS: The report describes a community-based model of care that is
      designed to provide affordable, age-appropriate, confidential, convenient care to
      adolescents, a population that traditionally has been very hard to reach. The
      SLHCs ability to provide reproductive health care makes it an attractive option
      for communities trying to prevent pregnancy and sexually transmitted diseases
      among adolescents. To firmly conclude that the SLHC is an effective model for
      improving adolescent access to services, more research is needed on adolescents'
      use and nonuse of SLHCs and other models of care; the cost of SLHCs compared to
      other models of care; and how SLHCs can sustain themselves financially,
      particularly in a managed care environment.

PMID- 9648021
TI  - Variations in HIV risk behaviors of incarcerated juveniles during a four-year
      period: 1989-1992.
AB  - OBJECTIVE: To retrospectively monitor over several years change in incarcerated
      juveniles' human immunodeficiency virus (HIV) risk behaviors. METHODS: From 1989
      to 1992, detainees who volunteered after an HIV class or were referred by a
      health care provider were counseled individually and privately by health
      educators using a standardized questionnaire and counseling form developed from
      an instrument used to counsel prostitutes in Los Angeles, California. RESULTS:
      The number counseled each year was 1045, 1745, 2354 and 1428 from 1989 to 1992,
      respectively. Those agreeing to HIV testing rose from 72% of total participants
      in 1989 to 84% of total participants in 1992. Eight of those youth tested as HIV
      positive. Four blind seroprevalence studies during the same time yielded one case
      in 1000 for 1988, one case in 1005 for 1989, two cases in 751 in late 1989
      (2.7/1000), and one case in 1214 for 1990 (1.25/1000). The number worrying about
      AIDS and considering themselves vulnerable to AIDS increased, but protective
      behaviors did not. Sexual partners per year were 2.1 regardless of the age of
      first sexual activity. Alcohol was associated with an increased number of sexual
      partners (2.6/year) and higher rates of sexually transmissible infections (STIs)
      and pregnancy. Although 96% of boys and girls were sexually active, only 4% used
      a condom consistently during the first 3 years, and only 7% in 1992. Those
      reporting having used condoms with the intention to prevent both STIs and
      pregnancy had a higher rate of use. Those carrying condoms all the time used
      condoms more often. Males having sex with both males and females rarely used
      condoms, and 45% had one or more STIs. CONCLUSIONS: Although the rate of HIV
      infection remains low in juveniles detained by the County of Los Angeles, their
      rates of risky behaviors place them at high risk for HIV acquisition.

PMID- 9648022
TI  - Adolescent emotional response to music and its relationship to risk-taking
      behaviors.
AB  - PURPOSE: Adults have frequently been concerned about the adverse influence that
      music may have on teenagers. This study was designed to examine the relationship
      between the intensity of emotional response to music and health risk-taking
      behavior in adolescents. METHODS: Consecutive participants from the University of
      California, San Diego, Adolescent Medicine Clinics completed a written survey
      about music preference, emotional response to music using the Positive Affect
      Negative Affect Schedule (PANAS), and a variety of health-risk behaviors. For
      each participant, the PANAS scores were summed to give a positive, negative, and
      total affect score, and health-risk behaviors were assigned a point value based
      on the level of risk and then summed to give a risk score. RESULTS: Health-risk
      behavior was found to be correlated with increasing emotional response to music
      (r = 0.23), whether those emotions were positive (r = 0.19) or negative (r =
      0.24). Strong negative emotional response to music in particular was correlated
      with a history of greater risk behavior, particularly among whites (risk score =
      14.0). CONCLUSIONS: Our study indicates that subjects who experience strong
      negative emotions to music are at an increased risk of participating in a variety
      of risk-taking behaviors. Further evaluation of the link between emotional
      response to music and health-risk behaviors will be useful in clarifying the
      nature of this relationship.

PMID- 9648023
TI  - Nipple and areola diameter in Turkish pubertal girls.
AB  - The nipple and areola diameter of 498 girls aged 8-17 years were studied with the
      aim of finding measurable criteria for sexual maturation, including breast and
      pubic hair development during female puberty. All measurements were made holding
      a transparent ruler on both sides by the same observer. The smaller of the two
      measurements was used in the analysis. Significantly nipple and areola
      development occurred between breast stages B1 (2.56 and 14.35 mm), B2 (3.32 and
      20.26 mm), B3 (5.21 and 28.84 mm), and B4 (6.28 and 32.03 mm). The nipple and
      areola diameter were also significantly greater in pubic hair stage (PH)3 (5.05
      and 25.24 mm) with respect to PH2 and PH1 (3.46, 2.62 mm and 19.32, 15.37 mm,
      respectively), in PH5 (6.79 and 35.62 mm) with respect to PH4 (6.55 and 32.56
      mm). A significant increase in nipple and areola diameter occurs between
      premenarchal girls and girls older than 0-2 years postmenarche. Sexual maturation
      staging by nipple size and by areola size appears to be feasible for female
      adolescent. However, staging by nipple size does not appear to be feasible for B4
      and B5 stage, because the incremental gradations are small.

PMID- 9648024
TI  - Chemical modification and photograft polymerization upon expanded
      poly(tetrafluoroethylene).
AB  - Poly(tetrafluoroethylene) (PTFE) films were surface-modified by employing a
      reaction solution of benzophenone and sodium hydride in anhydrous
      dimethylformamide at a temperature of 150 degrees C for 12 h. Electron
      spectroscopy for chemical analysis (ESCA) showed defluorination, oxygen
      incorporation, and extensive unsaturation within the treated PTFE surfaces. The
      suitably of these reduced PTFE films as substrates for graft polymerization was
      initially assessed via photograft polymerization of the sodium salt of
      styrenesulfonic acid (SS-Na), which permitted unequivocal surface analysis by the
      introduction of a new atom, as well as poly(ethylene glycol) monoacrylate (PEG
      Ac). All photograpt polymerization was performed employing ultraviolet
      irradiation with 2,2-dimethoxy-2-phenylacetophenone as an initiator. Photograft
      polymerization of SS-Na was verified by further reduction of fluorine atomic
      content and the appearance of new sulfur and sodium atomic peaks on ESCA survey
      spectra, and that of PEG-Ac was verified by further reduction of fluorine atomic
      content and increase of atomic percent ratio of O/C from ESCA survey spectra as
      well as appearance of a new ester peak on high resolution ESCA C 1s spectra.
      Dynamic water contact angles on reduced and PEG-Ac photograft polymerized films
      were measured and showed that the PTFE film surface became more hydrophilic after
      reduction (from 120 to 89 deg) and the reduced film became more hydrophilic after
      photograft polymerization with PEG-Ac (from 89 to 36 deg). Modification of the
      complete surface of expanded PTFE (ePTFE), i.e. of the lumenal, outside and pore
      surfaces, was performed by employing the reaction described above, except at 105
      degrees C for 1 day, followed by photograft polymerization of PEG-Ac. ESCA was
      performed on the superficial surfaces (i.e. the lumen and exterior) as well as on
      cross-sections of the ePTFE to permit analysis of the pore surfaces. This
      analysis showed that both the initial surface reduction and subsequent photograft
      polymerization were successful as indicated from F/C and O/C atomic percent
      ratios from ESCA survey spectra, from overall peaks shapes of high resolution
      ESCA C 1s spectra and from generation of new ester peaks on high resolution ESCA
      C 1s spectra of ePTFE graft polymerized with PEG-Ac, which demonstrated an O/C
      atomic percent ratio close to that of PEG-Ac homopolymer. Low voltage scanning
      electron microscopy confirmed minimal morphological damage to the ePTFE
      microstructure after reduction and graft polymerization. The approach explored
      thus provides a means for modulation of biological interactions at ePTFE surfaces
      with only minimal modification of material morphology, with some surface texture
      appearing on a length scale of 50-100 nm.

PMID- 9648025
TI  - Surface grafting of poly(ethylene glycol) onto poly(acrylamide-co-vinyl amine)
      cross-linked films under mild conditions.
AB  - Poly(ethylene glycol) (PEG) was grafted onto poly(acrylamide-co-vinyl amine)
      (poly(AM-co-VA)) film using tresylated PEG (TPEG) at 37 degrees C in aqueous
      buffers (pH 7.4) with a view to surface-modifying microencapsulated mammalian
      cells. Poly(AM-co-VA) film was synthesized by Hofmann degradation of a cross
      linked poly(acrylamide) film. Conversion to vinyl amine on the surface of the
      film was approximately 50%, but bulk conversion was not observed; surface
      specificity was thought to be the result of cleavage of aminated polymer chains
      at the surface due to chain scission. Reaction between primary amine and TPEG
      gave a graft yield of 2 mol% (based on XPS) with respect to available surface
      amine groups, equivalent to 54 mol% ethylene oxide based on monomer units.
      Physical adsorption of non-activated polymer was done under identical conditions
      as a control and the difference in oxygen content was significant compared to
      TPEG. The type of buffer agent and buffer concentration did not influence graft
      yields. This graft reaction, which was completed in as little as 2 h was
      considered to be mild enough to be used for a surface modification of
      microcapsules containing cells without affecting their viability. Such a surface
      modification technique may prove to be a useful means of enhancing the
      biocompatibility of microcapsules (or any tissue engineering construct) even
      after cell encapsulation or seeding.

PMID- 9648026
TI  - Ectopic bone formation induced by biodegradable hydrogels incorporating bone
      morphogenetic protein.
AB  - Biodegradable hydrogels were prepared from gelatin by glutaraldehyde cross
      linking for release matrix of recombinant human bone morphogenetic protein-2 (BMP
      2). BMP-2 solution was impregnated into the dried hydrogels to prepare BMP-2
      incorporating gelatin hydrogels. In the in vitro study, enhanced retention of BMP
      2 was observed from the BMP-2-incorporating gelatin hydrogels after an initial
      burst of BMP-2 incorporated initially in the hydrogel. Following subcutaneous
      implantation of (125)I-labeled BMP-2-incorporating gelatin hydrogels in the back
      of mice, the radioactivity remaining in the hydrogels was measured to estimate
      the in vivo release profile of BMP-2. It was found that BMP-2 was retained in the
      hydrogels for longer than 30 days, whereas 99% of BMP-2 injected in the solution
      form was cleared from the injected site within one day, completely disappearing
      within 3 days. Ectopic bone formation studies demonstrated that BMP-2
      incorporating gelatin hydrogels exhibited a more potent ability for bone
      induction than solution injection of BMP-2. This finding indicates that enhanced
      retention of BMP-2 is promotes its ability to induce ectopic bone formation.

PMID- 9648027
TI  - Complexation of basic fibroblast growth factor with gelatin.
AB  - Polyion complexation between basic fibroblast growth factor (bFGF) and gelatin
      was studied by the turbidity change of mixed solution, heparin high performance
      liquid affinity chromatography (HPLAC), and isoelectric electrophoresis. When an
      aqueous solution of acidic gelatin with an isoelectric point (IEP) of 5.0 was
      mixed with that of bFGF, the turbidity of the mixed solution increased with time,
      whereas basic gelatin with and IEP of 9.0 did not cause any solution turbidity. A
      maximum turbidity of the mixed bFGF and acidic gelatin solution was observed
      around a bFGF/gelatin molar ratio of 1.0, irrespective of the gelatin
      concentration and solution temperature. The solution turbidity decreased with an
      increase in the ionic strength of the mixed solution. Complexation of bFGF with
      acidic gelatin was slower than that with poly(acrylic acid) probably because of
      the lower density of gelatin negative charge than that of poly(acrylic acid).
      HPLAC study revealed that complexation of bFGF with the acidic gelatin reduced
      the affinity of bFGF for heparin, in contrast to the basic gelatin, although the
      extent became smaller with the increasing ionic strength of the solution. An
      electrophoretic experiment showed that the IEP of bFGF shifted to a lower value
      after its gelatin complexation. These findings indicate that an electrostatic
      interaction is the main driving force for the complexation between acidic gelatin
      and basic bFGF.

PMID- 9648028
TI  - Comparative study of the use of poly(glycolic acid), calcium alginate and
      pluronics in the engineering of autologous porcine cartilage.
AB  - New cartilage formation has been successfully achieved by technology referred to
      as tissue engineering. Polymers and hydrogels such as poly(glycolic acid),
      calcium alginate, and poly(ethylene) and poly(propylene) hydrogels have been used
      as cell carriers to regenerate cartilage in the nude mouse model. The next step
      toward human applications of engineered cartilage is to demonstrate their
      potential in immunocompetent animal models. This study compared the suitability
      of three polymers for generating tissue engineered elastic cartilage using
      autologous cells in an immuno-competent porcine animal model. Auricular cartilage
      was obtained from pigs. Chondrocytes were isolated onto fiber based poly(glycolic
      acid) (PGA) scaffolds or suspended in calcium alginate or pluronic F127 gel at
      constant concentrations. Chondrocyte-polymer constructs were either implanted
      (PGA) or injected (calcium alginate and pluronic) as autologous implants
      subcutaneously into the pigs from which the cells had been isolated. Specimens
      were harvested and analyzed grossly and historically after 6 weeks in vivo. All
      explants demonstrated cartilage formation to a variable degree. When using PGA or
      calcium alginate, the overall histological appearance of the tissue formed is
      that of fibrocartilage with thick bundles of collagen dispersed in the tissue.
      When using pluronics as scaffold, histologic features resemble those of native
      elastic cartilage, showing a more organized arrangement of the cells, which seems
      to correlate to functional properties as elastin presence in the tissue
      engineered cartilage. Elastic cartilage engineered in an immunocompetent animal
      model varies with the type of polymer used. The behavior of the cell-polymer
      constructs is not fully understood and outcome seems to be related to several
      factors, including inflammatory reaction. Further studies with similar models are
      needed to determine the feasibility of engineering tissue generated from
      different cell-polymer constructs prior to human application.

PMID- 9648029
TI  - Periodontal ligament cell culture on the hydrophobic substrate coated with
      proteins of periodontal ligament fibroblast-conditioned medium.
AB  - In regenerating periodontal ligament (PDL) around the root of an artificial
      tooth, an important role is played by some physiologically active substance that
      promotes adhesion of the cells to the surface of the tooth root and induces cell
      proliferation and differentiation. In this study, the supernatant of the
      conditioned medium (CM) of dog periodontal ligament fibroblast (DPLF) was
      fractionated using an ion exchange chromatography-diethylaminoethyl (IEC-DEAE)
      column. DPLFs were cultured on hydrophobic dishes coated with each fraction. Cell
      proliferative activity and alkaline phosphatase (ALPase) activity, including
      electron microscopic features of the contact surface between the cells and the
      dish, were investigated. The DPLF-CM was separated by IEC-DEAE column into six
      fractions. Each fraction promoted an increase in DNA content and ALPase activity
      of the cultured DPLF, and especially remarkable were fractions 2 and 3. Fraction
      2 at a molecular weight (Mw) of 210, 160, 85, 50 and 22 kD, and fraction 3 at Mw
      = 21 and 23 kD contained the type of proteins not found in other fractions.
      Electron microscopic analysis revealed that the cells in the coating group were
      in close contact with the surface of the dishes and that fine fibers protruding
      from the cell membrane clinged to the dishes. In the control group, a wide gap
      between the cells and the dishes was observed. These findings suggest that the
      DPLF-CM fractions contain specific physiological activating factors that induce
      proliferation and differentiation as well as cell adhesion of the DPLF cells.

PMID- 9648030
TI  - Creating biomimetic micro-environments with synthetic polymer-peptide hybrid
      molecules.
AB  - In designing polymers that can act as tissue engineering templates it is
      beneficial to consider methods of mimicking the natural support structures used
      by the human body to guide the behavior and development of cells within tissues.
      The well-known RGD cell adhesion ligand provides a simple mechanism of creating
      polymer surfaces that mimic the extracellular matrix. This paper considers the
      methods that have been used to attach such motifs to synthetic polymers. In
      general there are two strategies: the formation of polymer-peptide hybrid
      molecules, or the immobilization of the ligand on the fabricated surface of the
      polymer. The three major synthetic strategies of creating polymer-peptide hybrids
      are reviewed.

PMID- 9648031
TI  - Empirically supported psychosocial interventions for children: an overview.
AB  - Discusses issues related to the identification of psychosocial interventions for
      children that have demonstrated efficacy. Recent debate concerning differences
      between clinical trials research and clinical practice is summarized, including
      the tradeoff between interpretability (internal validity) and generalizability
      (external validity) of outcome studies. This article serves as an introduction to
      the special issue containing articles that have as their focus the identification
      of empirically supported psychosocial interventions for children as part of a
      task force. The article provides an overview of the history, agenda, and
      methodology used by the task force to define and identify specific empirically
      supported interventions for children with specific disorders. Whereas a number of
      well-established or probably efficacious interventions are identified within the
      series, more work directed at closing the gap between research and practice is
      needed.

PMID- 9648032
TI  - Applying the criteria for empirically supported treatments to studies of
      psychosocial interventions for child and adolescent depression.
AB  - Reviews the psychosocial treatment outcome studies for depressed children and
      adolescents and concludes that psychosocial interventions are effective at
      posttreatment and follow-up in reducing depressive symptoms/disorders in clinical
      and nonclinical samples of youth, regardless of treatment modality or extent of
      parental involvement. The article then examines the extent to which each study
      conforms to the guidelines set forth by the Task Force on Promotion and
      Dissemination of Psychological Procedures (1996) for well-established and
      probably efficacious interventions. Results of this analysis indicate only 2
      series of studies that meet criteria for probably efficacious interventions and
      no studies that meet criteria for well-established treatments. Finally, the
      advantages and disadvantages of applying criteria for empirically supported
      treatments to identify good treatments for depressed youth are discussed, the
      importance of devising developmentally and culturally sensitive interventions
      targeted to the unique needs of each child is highlighted, and recommendations
      for future research that is informed by clinical practice and empirical findings
      are offered.

PMID- 9648033
TI  - Empirically supported treatments for children with phobic and anxiety disorders:
      current status.
AB  - Reviews the empirically supported status of behavioral and cognitive-behavioral
      interventions in the treatment of childhood phobias and anxiety disorders. For
      childhood phobias, it is concluded that imaginal desensitization, in vivo
      desensitization, filmed modeling, live modeling, and cognitive-behavioral
      interventions that use self-instruction training are probably efficacious and
      that participant modeling and reinforced practice are well established. For
      anxiety disorders, only cognitive-behavioral procedures with and without family
      anxiety management (FAM) were found to be probably efficacious. However, much of
      the support for these procedures comes from analogue studies conducted in
      research laboratory or school settings, delivered in small-group format and, not
      infrequently, with nonclinically referred children. Additional research that
      examines high-strength interventions with clinic-referred children is
      recommended. Furthermore, research that examines the pathological processes
      involved in the onset and maintenance of phobic and anxiety disorders as well as
      the change processes used to treat these disorders is called for.

PMID- 9648034
TI  - Empirically supported comprehensive treatments for young children with autism.
AB  - Describes treatment of autism, a severe, chronic developmental disorder that
      results in significant lifelong disability for most persons, with few persons
      ever functioning in an independent and typical lifestyle. Within the past decade,
      a number of studies have reported significant changes in the outcomes of very
      young children with autism following intensive comprehensive treatment. The
      criteria for empirically supported treatments, as described by Lonigan, Elbert,
      and Johnson (this issue), were applied to reports of eight treatment efficacy
      studies published in peer-reviewed journals. Whereas positive outcomes are
      reported in every case, the field does not yet have a treatment that meets the
      present criteria for well-established or probably efficacious treatment.
      Hypothesized variables affecting outcomes that need to be rigorously tested
      include age at start of treatment, type of treatment used, intensity of
      treatment, and IQ and language levels at the start of treatment.

PMID- 9648035
TI  - Effective psychosocial treatments of conduct-disordered children and adolescents:
      29 years, 82 studies, and 5,272 kids.
AB  - Reviews psychosocial interventions for child and adolescent conduct problems,
      including oppositional defiant disorder and conduct disorder, to identify
      empirically supported treatments. Eighty-two controlled research studies were
      evaluated using the criteria developed by the Division 12 (Clinical Psychology)
      Task Force on Promotion and Dissemination of Psychological Procedures. The 82
      studies were also examined for specific participant, treatment, and
      methodological characteristics to describe the treatment literature for child and
      adolescent conduct problems. Two interventions were identified that met the
      stringent criteria for well-established treatments: videotape modeling parent
      training program (Spaccarelli, Cotler, & Penman, 1992; Webster-Stratton, 1984,
      1994) and parent-training programs based on Patterson and Gullion's (1968) manual
      Living With Children (Alexander & Parsons, 1973; Bernal, Klinnert, & Schultz,
      1980; Wiltz & Patterson, 1974). Twenty of the 82 studies were identified as
      supporting the efficacy of probably efficacious treatments.

PMID- 9648036
TI  - Empirically supported psychosocial treatments for attention deficit hyperactivity
      disorder.
AB  - Reviews and evaluates psychosocial treatments for attention deficit hyperactivity
      disorder (ADHD) in children and adolescents according to Task Force Criteria
      (Lonigan, Elbert, & Johnson, this issue). It is concluded that behavioral parent
      training and behavioral interventions in the classroom meet criteria for well
      established treatments. Cognitive interventions do not meet criteria for well
      established or probably efficacious treatments. Issues regarding the evaluative
      process are discussed and future directions for psychosocial treatment for ADHD
      are outlined.

PMID- 9648037
TI  - Finding, evaluating, refining, and applying empirically supported treatments for
      children and adolescents.
AB  - Structured child and adolescent treatments, tested through controlled clinical
      trials, have produced beneficial effects in hundreds of studies. By contrast, the
      limited pool or research on traditional clinical treatments raises doubts about
      their effectiveness. Thus, identification of empirically supported treatments may
      contribute something of real value to clinical practice and training. The Child
      Task Force report represents an important initial step in this direction. Here we
      offer both praise and critique, suggesting a number of ways the task force
      process and product may be improved. In addition, we suggest several ways to
      strengthen and enrich the clinical trials research available to the Task Force,
      emphasizing the need to test empirically supported treatments with referred youth
      in practice settings.

PMID- 9648038
TI  - Current progress and future plans for developing effective treatments: comments
      and perspectives.
AB  - Examined the conclusions and implications of articles in this special issue.
      Treatments can be differentiated on their empirical basis and, for the problems
      reviewed, one can identify treatments of choice. To build on the documented
      advances, we provide a blueprint for progress in treatment research. The
      blueprint focuses on a series of steps that involve conceptualization of clinical
      dysfunction and treatment, supportive research on these conceptual views, careful
      specification of treatment, evaluation of treatment outcome, and tests of
      mediators and moderators of treatment. To improve research, we recommend
      expanding assessment, addressing a broad range of questions about treatment,
      attending to measures of clinical significance, replicating key findings, and
      investigating the transportability of the findings to service-oriented clinical
      settings.

PMID- 9648039
TI  - Psychosocial determinants of alcohol use among minority youth living in public
      housing developments.
AB  - Youth residing in low income, inner city, public housing developments might be
      extremely vulnerable to psychosocial risk factors associated with alcohol use. In
      this study, we developed and tested a model of alcohol etiology with 624 African
      American and Hispanic 7th graders residing in public housing developments. The
      students completed questionnaires concerning their alcohol use, social influences
      on their drinking, their drinking attitudes and knowledge, their psychosocial
      skills, and demographic and behavioral control information. Logistic regression
      analyses indicated that social influences from adults, friends, and family
      members predicted alcohol use. Individual psychosocial characteristics, e.g.,
      drinking refusal, lowered the odds of drinking. These findings imply that
      effective prevention approaches targeting minority urban youths residing in
      public housing developments should provide them with an awareness of social
      influences to drink, correct misperceptions concerning the prevalence of
      drinking, and train them in relevant psychosocial skills.

PMID- 9648040
TI  - Infant screening: the usefulness of the Bayley Infant Neurodevelopmental Screener
      and the Clinical Adaptive Test/Clinical Linguistic Auditory Milestone Scale.
AB  - We assessed the usefulness of the Bayley Infant Neurodevelopmental Screener
      (BINS) and the Clinical Adaptive Test/Clinical Linguistic Auditory Milestone
      Scale (CAT/CLAMS) for screening high-risk infant populations in a sample of 78
      infants followed after premature birth and/or perinatal insults. Both measures
      were highly correlated with the Bayley Scales of Infant Development-II, but
      sensitivity and specificity analyses revealed disparities related to the tests
      administered and the cutoffs used. The BINS had optimal sensitivity (true
      positives) of 90% when referral was made for a BINS score of high or moderate.
      The CAT/CLAMS had excellent specificity (true negatives) of 95% to 98% but poor
      sensitivity (5%-36%). Until the cutoff issue can be clarified, clinicians should
      be cautious in using the CAT/CLAMS as the primary screening instrument in
      settings in which early identification of infants with developmental problems is
      the main goal.

PMID- 9648041
TI  - Examination of DSM-IV criteria for attention deficit/hyperactivity disorder in a
      county-wide sample.
AB  - This study replicated, in the subsequent academic year, teacher-reported
      prevalence rates for attention deficit/hyperactivity disorder (ADHD) based on DSM
      IV. Teachers in grades K-5 in a Tennessee county (10 schools, 214 teachers, and
      4323 children) completed questionnaires on all their students consisting of the
      DSM-IV symptoms for disruptive behavior disorders, except for eight conduct
      disorders symptoms, seven symptoms screening for anxiety or depression, ratings
      of performance, and questions about the presence of ADHD, stimulant medication
      treatment, and behavioral or academic problems. The prevalence rates were 16.1%
      for ADHD-all types, 8.8% for ADHD-inattentive type (AD), 2.6% for ADHD
      hyperactive/impulsive type (HI), and 4.7% for ADHD-combined type and 6.8, 3.2,
      0.6, and 2.9%, respectively, when impairment was taken into consideration. The
      rates of problems differed mostly between ADHD-AD AND ADHD-HI (30% vs. 68%) for
      behavior and (56% vs. 16%) for academics. Few (11-33%) had an ADHD diagnosis or
      were treated with stimulant treatment (8-26%). DSM-IV criteria are likely to
      increase the prevalence but may better characterize the heterogeneity of this
      disorder.

PMID- 9648042
TI  - Infant predictors of cognitive development in an undernourished Kenyan
      population.
AB  - Assessments of infant sociability, motoric capacities, and nutritional factors
      were performed to elucidate early influences on infant development in an
      undernourished Kenya population. In this longitudinal study, infant social skills
      were assessed using both the Bayley Behavior Record and home observations during
      the first 6 months of the infants' lives. Abilities were measured using an
      adapted version of the Bayley scales of infant development at 6 and 30 months,
      and a short battery of cognitive measures at 5 years. Infant size measurements
      were used as indicators of infant nutritional status. Shorter and lighter
      infants, and those infants showing growth faltering in weight attainment, were
      significantly less sociable at 6 months than infants who were taller and
      maintained heavier weights. Infants with smaller arm circumferences displayed
      lower motor scores at 6 months and lower Bayley mental scores at 30 months than
      infants with greater arm circumference. Furthermore, infants who were more
      motorically able and socially adept at 6 months had higher Bayley scores at 30
      months and higher verbal comprehension scores at 5 years.

PMID- 9648043
TI  - Parental report of sleep problems in children with attentional and learning
      disorders.
AB  - This study examined whether parents of children diagnosed with neurodevelopmental
      disorders (n = 79) report greater sleep-related problems in their offspring than
      do parents of normal community-based children (n = 86) on a research
      questionnaire developed to assess sleep and breathing problems, sleepiness, and
      behavioral problems. Clinical subgroups included: attention deficit/hyperactivity
      disorder (ADHD) (n = 43), learning disabilities (LD) (n = 11), and combined
      ADHD/LD (n = 25). Analyses revealed that parents of children with
      neurodevelopmental disorders report greater problems along all three dimensions
      than parents of normal control children. Sleep-related difficulties were reported
      at the same frequency across all three clinical subgroups. No significant
      difference between clinical and control groups was noted, however, in the
      reported length of sleep on weeknights. These preliminary findings suggest that
      sleep-related problems need to be routinely reviewed as part of the clinical
      evaluation of neurodevelopmental problems, because they may contribute to and/or
      exacerbate the behavioral manifestation of these disorders.

PMID- 9648044
TI  - Stimulant use and the potential for abuse in Wisconsin as reported by school
      administrators and longitudinally followed children.
AB  - The purpose of this study was to describe stimulant use and abuse as reported by
      school administrators and children diagnosed with attention deficit/hyperactivity
      disorder or attention deficit disorder inattentive. Five years after being
      identified as Ritalin responders, 161 children were surveyed regarding stimulant
      use and abuse. School principals in central Wisconsin were also surveyed
      regarding stimulant use and policies. No child believed stimulants as prescribed
      could lead to abuse. Sixteen percent of the children had been approached to sell,
      give, or trade their medication. During school hours, 44% of children and 37% of
      schools reported stimulants were stored unlocked. Not all schools had written
      policies regarding prescription drugs, and 10% permitted students to carry their
      own medication. Monitoring prescription usage, periodic reassessment of efficacy,
      and continuing education of family and teaching staff should be part of the
      multimodal treatment for this disorder. School policies should be developmentally
      sensitive.

PMID- 9648045
TI  - Pediatric pain management: program description and preliminary evaluation results
      of a professional course.

PMID- 9648046
TI  - Twelve-year-old girl with chronic fatigue, school absence, and fluctuating
      somatic symptoms.

PMID- 9648047
TI  - Psychological aspects of sexually transmitted infection acquisition in adolescent
      girls: a developmental perspective.

PMID- 9648048
TI  - Apoptosis and PCNA expression induced by prolactin in structural involution of
      the rat corpus luteum.
AB  - There are two stages of luteal regression. The first stage is functional
      regression that is characterized by a decreased production of progesterone
      secretion; the second stage of structural involution is referred to as a
      structural luteolysis. In rodents, prolactin has a biphasic action on the corpus
      luteum. It is luteotrophic, but when exposed to functionally regressed corpora
      lutea it causes luteolysis. The objective of the present studies was to examine
      mechanisms of prolactin action in structural luteolysis, whether apoptosis is
      involved in this process, and to examine the possible association of cell
      proliferation signals as mediators of structural luteolysis. Prolactin-induced
      structural luteolysis was associated with apoptosis verified by terminal
      deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling
      (TUNEL). Apoptotic cells made up about 3% of the cells 24 hours after the first
      injection of prolactin, a level that remained constant at all stages of
      structural luteolysis. Total ovarian weight and DNA content were decreased about
      50% in 72 hours after induction of structural luteolysis by prolactin, The
      finding of about 3% of cells in apoptosis indicates apoptosis is a rapid process.
      Proliferating cell nuclear antigens (PCNA) of luteal cells were significantly
      decreased during functional luteal regression, but were conversely increased in
      structural luteolysis as shown by western blotting and immunohistochemistry. In
      general PCNA expression is reported to be decreased during structural involution,
      and there are no reports that have linked excess expression of PCNA with
      apoptosis and structural luteolysis. We speculate that an excessive increase in
      expression of PCNA which signals activation of cell proliferation creates a
      disorder in the signals involved with DNA synthesis. This disorder results in
      mitotic catastrophe and in the induction of apoptosis. Therefore the disorder of
      cell cycle signals in luteal cells are associated with prolactin induced
      apoptosis in structural luteolysis.

PMID- 9648049
TI  - Effect of surgery and radiotherapy on visual and endocrine function in
      nonfunctioning pituitary adenomas.
AB  - The effect of surgery alone or followed by radiotherapy in recovering visual
      abnormalities, debulking tumor mass and restoring hormone impairments was
      evaluated in 84 patients with clinical nonfunctioning pituitary adenomas (NFPA)
      subjected to 1-10 yr follow-up. All patients underwent surgery via
      transsphenoidal (in 69) or transcranic-pterional approach (in 15). Radiotherapy
      was performed after surgery in 59 of 72 patients with incomplete tumor removal.
      The assessment of pituitary function was performed in all patients before and
      every 1-2 yr after surgery and/or radiotherapy. Radiological and ophthalmologic
      assessment was performed before and 3, 6 and 12 months after surgery, then
      yearly. At diagnosis, headache and visual disturbances occurred in 63 and 58
      patients, respectively, while deficiency of GH, TSH, ACTH, FSH, LH and ADH was
      documented in 55, 7, 19 47 and 6 patients, respectively. After surgery, gonadal
      function recovered in 12 women, visual disturbances improved in 43 patients (15
      regained normal vision), pituitary function improved in 8 of 62 patients,
      worsened in 34 patients. At MRI, complete tumor removal was documented in 12 of
      84 patients. After surgery alone, tumor regrowth was observed in 7 patients
      between 3-7 yr. After radiotherapy, vision improved in 9, remained unchanged in
      49 and worsened in 1 of 59 patients. After radiotherapy, tumor regrowth was
      documented in 9 patients between 2-12 yr and the prevalence of hypopituitarism
      raised from 28.8% to 92% after 1 and 10 yr. In conclusion, surgery alone is
      effective only in a minority of patients (14.3%) and radiotherapy causes
      hypopituitarism in rather the totality of patients after 10 yr. The prevalence of
      tumor regrowth was similar in irradiated ones (15%) and non irradiated patients
      (28%; chi(2), p = 0.4). Therefore, a careful radiological followup is suggested
      after surgery so that radiotherapy can be performed promptly on the basis of
      clinical data, tumor regrowth and/or invasiveness documented at histology.

PMID- 9648050
TI  - Lack of effect of the dopamine D1 antagonist, NNC 01-0687, on unstimulated and
      stimulated release of anterior pituitary hormones in males.
AB  - Dopamine in humans inhibits the secretion of luteinizing hormone (LH), follicular
      stimulating hormone (FSH), thyroid stimulating hormone (TSH) and prolactin (PRL),
      and is a stimulator of growth hormone (GH) secretion. Dopamine-D1 receptor
      stimulation with fenoldopam increases basal PRL levels, suppresses TSH, and
      increases gonadotropin releasing hormone (LHRH) induced LH release. We have
      investigated the effect of a dopamine D1-receptor antagonist, NNC 01-0687, on the
      secretion of anterior pituitary hormones. In 8 healthy males NNC 01-0687 and
      placebo were administered orally in a double-blind placebo controlled cross-over
      study for three days with a wash-out period of 14 days. Hormonal responses (PRL,
      LH, FSH, GH, TSH, thyroid hormones and testosterone), unstimulated and LHRH/TRH
      stimulated, were studied on days 1 and 3. No significant difference (p > 0.05)
      between placebo and active periods was found neither in unstimulated nor in
      stimulated hormone concentrations expressed in absolute values, percent change of
      before, incremental values and area under the curve. These results suggest that
      the neuronal DA-D1 activity is not activated during basal conditions in healthy
      male subjects.

PMID- 9648051
TI  - Pituitary apoplexy in acromegaly, a long-term follow-up study in two patients.
AB  - Pituitary apoplexy is a serious complication in about 3% of patients with a
      pituitary adenoma. Very often, the diagnosis of a functioning or non-functioning
      adenoma is made in retrospect. In this report, we describe two patients in whom
      the diagnosis of acromegaly was made before the apoplexy. In one patient,
      surgical intervention was necessary because of remaining clinical and biochemical
      activity; in the other patient conservative follow-up was pursued. Seven and nine
      years after apoplexy, respectively, the patients were clinically and
      biochemically in remission. During the follow-up, three and five years after
      apoplexy, respectively, the patients underwent a 10-min venous sampling procedure
      for 24 hours, and the GH secretory profile was investigated with multiparameter
      deconvolution analysis and by approximate entropy (ApEn), a scale- and model
      independent regularity measure. The deconvolution analysis revealed an increased
      basal (nonpulsatile) GH secretion rate, while the total 24 h secretion rate was
      normal compared with 13 healthy male control subjects. ApEn was much larger for
      each patient than for any control subject value, indicating markedly more
      irregular GH secretion. We hypothesize that these subtle abnormalities are caused
      by non-specific damage as a result of vascular insult, leading to abnormal
      vascular supply, or abnormal autocrine and paracrine GH regulation within the
      remaining gland.

PMID- 9648052
TI  - Typical hormonal profiles are accompanied by increased immunoreactivity of theca
      folliculi steroid 17 alpha-hydroxylase P450 in polycystic ovary syndrome.
AB  - The localisation and expression of steroid 17 alpha-hydroxylase had been studied
      in ovaries obtained from 40 patients in whom polycystic ovary syndrome (PCO) was
      diagnosed, and in 15 normal ovaries. In patients, elevated serum LH and
      testosterone and normal FSH, prolactin and dehydroepiandrosterone levels were
      recorded. Serum oestradiol concentration was slightly decreased.
      Immunohistochemical staining with the use of antibody directed against human
      cytochrome P450c17 (CYP17) revealed that in polycystic as well as in normal
      ovaries, steroid 17 alpha-hydroxylase is localised mainly in the thecal cells of
      atretic follicles and in the interstitial cells of the stroma. Greater intensity
      of the immunohistochemical reaction in the polycystic ovaries than in normal
      controls, indicates a higher concentration of CYP17 and suggests increased
      expression of steroid 17 alpha-hydroxylase. It is postulated that the increased
      expression of ovarian steroid 17 alpha-hydroxylase is an important contributory
      factor in the pathogenesis of PCO.

PMID- 9648053
TI  - Effects of long-term pravastatin treatment on spermatogenesis and on adrenal and
      testicular steroidogenesis in male hypercholesterolemic patients.
AB  - To evaluate the influence of an hydrophilic statin, pravastatin, on adrenal and
      testicular steroidogenesis and spermatogenesis, eight male hypercholesterolemic
      patients were studied. All patients observed a hypocholesterolemic diet and
      received placebo for 4 weeks followed by pravastatin (20 mg/die) for 6 months.
      Before, during (4th-5th week) and at the end (23th-24th week) of active
      treatment, CRH (1 microgram i.v.), ACTH (Synacthen 250 micrograms i.v.) and human
      CG (HCG 3000 IU i.m.) tests were performed in addition to semen analysis.
      Pravastatin significantly reduced total cholesterol (20.3%), calculated LDL
      cholesterol (24.6%) and apolipoprotein B (10.5%, increased apolipoprotein A1
      (16.1%) and did not influence plasma HDL-cholesterol and triglycerides. Basal
      plasma cortisol, aldosterone, androstenedione, testosterone and oestradiol did
      not change under active treatment. Pravastatin administration affected neither
      adrenal hormone responses to CRH and ACTH or testicular response to HCG nor
      spermatogenesis in respect of motility, morphology and sperm count. In
      conclusion, long-term pravastatin treatment, at doses effective in improving
      lipid profile, did not influence testicular reproductive and endocrine function
      and did not interfere with basal and stimulated adrenal activity of male
      hypercholesterolemic patients.

PMID- 9648054
TI  - Urinary free deoxypyridinoline levels during childhood.
AB  - Free urinary deoxypyridinoline (DPD) levels, corrected for the urinary
      concentration of creatinine (nmol/mmol), were determined in 144 healthy children
      (76 males and 68 females, mean age +/- SE: 9.1 +/- 0.2 yr, age range: 5.1-14.0
      yr) in order to detect the possible age-related changes of this reliable index of
      bone resorption activity and the relationship between free DPD, gender and
      pubertal development. Multiple regression analysis revealed that most of the
      variation in DPD levels was explained by chronological age (coefficient: 2.89, p
      < 0.02), whereas sex and pubertal stage did not add significance to the variance.
      Urinary DPD levels were similar in males (24.7 +/- 1.8 nmol/mmol urinary
      creatinine) and females (24.2 +/- 2.0 nmol/mmol urinary creatinine) and
      significantly higher (p < 0.02) in pubertal (Tanner stage II-V: 28.6 +/- 2.8
      nmol/mmol urinary creatinine) than in prepubertal children (22.4 +/- 1.4
      nmol/mmol urinary creatinine), both in males and in females. The pattern of DPD
      levels was clearly different between females and males, the maximum increase
      being evident at Tanner stage II-III (mid-puberty) in females and at Tanner stage
      IV-V (mid-late puberty in males. The increase of DPD paralleled the elevation of
      urinary GH (pmol/mmol urinary creatinine), a non-invasive and acceptable index of
      physiological GH secretion, observed during the pubertal growth spurt. The
      progressive increase of urinary GH in older children was not followed by a
      further stimulation of bone resorption. Although the relationships between
      urinary, GH and DPD need to be better investigated, it seems plausible to
      hypothesize that the determination of urinary free DPD, as a marker of GH action
      on bone, might have some potential in the follow-up of growth promoting
      treatments, such as GH.

PMID- 9648055
TI  - Extreme but asymptomatic hypergastrinemia with gastroparesis in a young woman
      with insulin dependent diabetes mellitus.
AB  - Overt diabetic gastroparesis is a rare long-term complication of diabetes,
      probably resulting from autonomic neuropathy of vagus nerve. It is now clear that
      neural damage plays a pivotal role in the pathogenesis of the disease. Some
      studies showed high basal gastrin levels in patients with diabetic gastroparesis,
      but the clinical meaning of this observation is still unclear. We report the case
      of a young woman with Insulin Dependent Diabetes Mellitus (IDDM) who was referred
      to evaluate nausea and vomiting associated to ketoacidosis. Our hypothesis of
      autonomic neuropathy with gastroparesis was confirmed. We observed a progressive
      increase in fasting gastrin concentration (20-fold normal values) in the absence
      of any clinical and laboratory signs of Zollinger-Ellison (ZE) syndrome. The
      increasing vomiting induced a severe state of cachexia, which required total
      parenteral nutrition for a long period. All therapeutic approaches were
      unsuccessful, and the patient rapidly died, suggesting a possible link between
      the severity of the clinical picture and the gastrin plasma levels.

PMID- 9648056
TI  - Cushing's syndrome complicated by multiple opportunistic infections.
AB  - The case history of a 56-year-old man is described who suffered from severe
      adrenocorticotrophic hormone (ACTH)-dependent Cushing's syndrome. The clinical
      course was complicated by simultaneous infections with Pneumocystis carinii,
      Staphylococcus aureus, Candida albicans, Aspergillus fumigatus and Herpes
      simplex, which proved to be fatal. A study of the literature shows that
      opportunistic infections in endogenous Cushing's syndrome are associated with
      severe cortisol excess and carry a high mortality. Opportunistic infections are
      most prevalent in the ectopic ACTH syndrome explained by the very high plasma
      cortisol concentrations in this condition. Infections with Aspergillus species,
      Cryptoccus neoformans, Pneumocystis carinii and Nocardia asteroides predominated.
      Cushing's syndrome with a very high plasma cortisol concentration causes a severe
      immunocompromized state. Prompt evaluation of the cause of the hypercortisolism,
      initiation of cortisol lowering therapy, primary prophylaxis for Pneumocystis
      carinii infection when plasma cortisol exceeds 2500 nmol L-1 and a search for
      concomitant infectious disease is recommended.

PMID- 9648057
TI  - Graves' disease after percutaneous ethanol injection for the treatment of
      autonomous thyroid adenoma.

PMID- 9648058
TI  - Ischemic renal diseases: new insights into old entities.
AB  - Vascular nephropathies are a steadily increasing cause of end-stage renal
      failure. Arterionephrosclerosis and arteriolonephrosclerosis are common features
      in the hypertensive patient. This is especially true for blacks of African
      descent, in whom hypertension and nephrovasculopathies are a major cause of renal
      insufficiency. That primary hypertension leads to renal vascular lesions,
      glomerular obsolescence and interstitial fibrosis has long been established. It
      should not, however, obscure the fact that renal vascular lesions can be observed
      in animal models as well as in some humans, especially young blacks, in the
      absence of, or anticipating the onset of hypertension. This leads to considering
      the hypothesis that nephroangiosclerosis might stem from a genetic defect in the
      renal vascular bed and that this defect is strongly associated with the
      hypertensive trait. Atherosclerotic renal disease is a major, potentially
      treatable cause of chronic renal disease is a major, potentially treatable cause
      of chronic renal failure, especially in whites. It leads to renal atrophy, but
      the ischemic kidney retains a vigorous potential for tubular cell regeneration,
      which pleads for early recognition and treatment. Recent data suggest that renal
      ischemia, be it due to renal artery stenosis or to cholesterol crystal embolism,
      ranks among the multiple causes of secondary focal segmental glomerulosclerosis.
      Irrespective of its initial mechanism, ischemia induces renal fibrosis, the
      pathophysiology of which is centered on increased generation of angiotensin II.
      Finally, renal vascular lesions are commonly observed in the course of various
      nephropathies, even in the absence of hypertension, and the relationship between
      these lesions and the unfavorable prognosis of glomerulopathies, especially
      primary focal-segmental glomerulosclerosis, membranous glomerulopathy and IgA
      glomerulonephritis, remains to be elucidated. Expanding knowledge of the spectrum
      of nephrovasculopathies opens perspectives for investigating, understanding and
      treating a major mechanism of progressive renal insufficiency.

PMID- 9648059
TI  - In vitro branching tubulogenesis: implications for developmental and cystic
      disorders, nephron number, renal repair, and nephron engineering.
AB  - Branching tubulogenesis of the ureteric bud is critically important for kidney
      development. Recent findings using three-dimensional cell culture systems for in
      vitro branching tubulogenesis are likely to shed light on the mechanisms of
      ureteric bud morphogenesis. Here, we try to unify these findings with those
      obtained using genetic approaches and organ culture of the embryonic kidney into
      a working model of ureteric bud branching tubulogenesis. It appears that the
      balance between branching tubulogenesis facilitating growth factors such as
      epidermal growth factor receptor ligands, hepatocyte growth factor, insulin-like
      growth factors, and inhibitory growth factors such as transforming growth factor
      beta family members may regulate branching morphogenesis. Growth factors induce
      epithelial cell proliferation, migration, and modulate the expression of a
      variety of proteins. Downstream in the growth factor-mediated tubulogenesis
      pathway, extracellular proteases, protease inhibitors, extracellular matrix
      proteins, and integrins are likely to act as effectors and regulators of
      branching tubulogenesis. Discussed in some detail are the relevance of insights
      gleaned from in vitro models of branching tubulogenesis to congenital urogenital
      abnormalities, cystic kidney diseases, oligonephropathies and hypertension,
      tubular cell regeneration after injury, and tubular engineering.

PMID- 9648060
TI  - Transplantation of developing metanephroi into adult rats.
AB  - BACKGROUND: Transplantation of developing metanephroi into adult hosts has been
      proposed as a means to augment host renal function. METHODS: We implanted whole
      metanephroi from embryonic day 15 (E15) rats subcapsularly in kidneys or into the
      omentum of non-immunosupressed adult rat hosts. At the time of implantation, some
      host rats underwent unilateral nephrectomy (UNX) or unilateral nephrectomy and
      partial contralateral renal infarction (1 1/2 NX). E15 metanephroi contained only
      metanephric blastema, segments of ureteric bud, and primitive nephrons with no
      glomeruli. RESULTS: Four to six weeks post-implantation, metanephroi from E15
      rats had enlarged, become vascularized, and had formed mature tubules and
      glomeruli. Ureters of metanephroi transplanted into the omentum were anastomosed
      to hosts' ureters that remained after UNX. Four weeks following
      ureteroureterostomy, the contralateral kidney was removed. Inulin clearances of
      seven metanephroi implanted into UNX hosts averaged 0.11 +/- 0.02
      microliters/min/100 g (2.42 +/- 0.70 microliters/min/g kidney wt) and the
      creatinine clearances averaged 0.65 +/- 0.18 microliters/min/100 g. Metanephroi
      weighed 71 +/- 15 mg (approximately 4% of the contralateral native kidney). The
      transplanted metanephroi were vascularized by arteries originating from the
      omentum. Both weights of transplanted metanephroi (145 +/- 24 mg) and inulin
      clearances of transplanted metanephroi (30.1 +/- 8.7 microliters/min/g kidney
      weight) were significantly increased in rats that underwent 1 1/2 NX compared to
      UNX. In contrast, transplantation of developed kidneys resulted in rejection.
      CONCLUSIONS: Our findings establish that functional chimeric kidneys develop from
      metanephroi transplanted in adult hosts.

PMID- 9648061
TI  - Obstructive nephropathy in the neonatal rat is attenuated by epidermal growth
      factor.
AB  - BACKGROUND: Obstructive nephropathy is a primary cause of renal failure in
      infancy. Chronic unilateral ureteral obstruction (UUO) in the neonatal rat
      results in reduced renal expression of epidermal growth factor (EGF), renal
      tubular epithelial (RTE) cell apoptosis and interstitial fibrosis. We wished to
      determine whether these changes could be prevented by exogenous administration of
      EGF. METHODS: Thirty-three Sprague-Dawley rats underwent UUO within the first 48
      hours of life, and received daily injections of either EGF (0.1 mg/kg/day) or
      saline (control) for the following seven days, after which obstructed and intact
      opposite kidneys were removed for study. These were compared to 11 sham-operated
      rats that received either no injections, EGF injections, or saline injections.
      Renal cell proliferation was determined by proliferating cell nuclear antigen,
      apoptosis was measured by the TUNEL technique, and the distribution of vimentin,
      clusterin, transforming growth factor-beta 1 (TGF-beta 1), and alpha-smooth
      muscle actin were determined by immunohistochemistry. Tubular dilation, tubular
      atrophy, and interstitial collagen deposition were quantitated by
      histomorphometry. RESULTS: Compared to controls, EGF treatment increased RTE cell
      proliferation in the obstructed kidney by 76%, decreased apoptosis by 80%, and
      reduced vimentin, clusterin and TGF-beta 1 immunostaining (all P < 0.05). EGF
      treatment reduced tubular dilation by 50%, atrophic tubules by 30%, and
      interstitial fibrosis by 50% (all P < 0.05). There was no significant effect of
      EGF on renal alpha smooth muscle actin distribution. There was no effect of
      saline or EGF injections on kidneys from sham-operated rats for any of the
      parameters studied. CONCLUSIONS: We conclude that EGF stimulates RTE cell
      proliferation and maturation and reduces apoptosis in the neonatal rat kidney
      subjected to chronic UUO. These effects may contribute to the reduction in
      tubular dilation, tubular atrophy, and interstitial fibrosis. By preserving renal
      development, administration of EGF attenuates the renal injury resulting from
      chronic UUO.

PMID- 9648062
TI  - Molecular genetics of cystinuria: mutation analysis of SLC3A1 and evidence for
      another gene in type I (silent) phenotype.
AB  - BACKGROUND: Cystinuria is a hereditary disorder that affects luminal transport of
      cystine and dibasic amino acids in kidney and small intestine. Three subtypes
      have been defined on the basis of urinary excretion of cystine in obligate
      heterozygotes. Mutations in the SLC3A1 gene have been associated with the Type I
      phenotype. METHODS: We investigated 20 cystinuria patients from Quebec (8 Type
      I/I, 9 Type I/III and 3 Type II/N) for mutations in SLC3A1. DNA was studied by
      Southern blotting and by the single strand conformation polymorphism (SSCP)
      protocol to identify mutations. Expression of mutations in Xenopus oocytes was
      performed to confirm the effect of missense mutations on cystine uptake. RESULTS:
      Six novel mutations (2 large deletions, a 2 bp deletion and 3 single bp
      substitutions) were identified on the Type I allele. Four missense mutations
      (T216M, S217R, R270L and I618M) were expressed in vitro; the first three changes
      significantly decreased uptake. CONCLUSIONS: Combined with our previous work, we
      have identified 15/16 mutations in SLC3A1 on Type I alleles in the eight Type I/I
      patients, but only one SLC3A1 mutation on the nine Type I alleles of the Type
      I/III patients. Therefore, we propose that the Type I phenotype could be caused
      by mutations in other, as yet unidentified cystinuria genes.

PMID- 9648063
TI  - Cystinuria subtype and the risk of nephrolithiasis.
AB  - BACKGROUND: Cystinuria patients may be classified into several subgroups based on
      the urinary phenotype of heterozygotes. However, the relative risk for
      nephrolithiasis and the prevalence of SLC3A1 mutations in these subgroups are
      unknown. METHODS: Urinary cystine excretion, age at onset of nephrolithiasis and
      nature of SLC3A1 mutations were assessed prospectively in 23 cystinuria patients
      identified primarily through the Quebec Newborn Screening Program. Probands were
      classified as to cystinuria subtype on the basis of parental urinary cystine
      excretion. RESULTS: For classical Type I/I cystinuria, both parents excrete
      cystine in the normal range and probands carry two mutations of the SLC3A1 gene
      in nearly every case. Between ages 1 to 7 years, mean cystine excretion was high
      (4566 +/- 480 microns cystine/g creatinine) and exceeded the theoretic threshold
      for solubility on 70% of visits. Four of eight Type I/I patients began forming
      stones in the first decade. Type I/III patients (N = 12) excreted less cystine
      (1544 +/- 163 mumol cystine/g creatinine), exceeded the threshold of urinary
      cystine solubility less frequently (22% of visits) and had no nephrolithiasis in
      the first decade; one formed a stone at age 16 years. Only one SLC3A1 mutation
      was identified in this group. Two Type II/N cystinuria children were identified.
      In these families, the same level of relatively high excretion (> 600 mumol
      cystine/g creatinine) was noted in two or three generations, but no SLC3A1
      mutations were identified. CONCLUSIONS: Classical recessive Type I/I cystinuria
      is genetically and phenotypically distinct from the other subtypes (Type I/III
      and Type II/N) identified in our population.

PMID- 9648064
TI  - Cytokine interactions promote synergistic fibronectin accumulation by mesangial
      cells.
AB  - BACKGROUND: The development of glomerulosclerosis has been associated with the
      presence of the cytokines transforming growth factor-beta 1 (TGF-beta 1), tumor
      necrosis factor-alpha (TNF-alpha) and/or interleukin-1 beta (IL-1 beta), at some
      stage in the glomerulus. To better understand the role of these cytokines in the
      scarring process their effect on rat mesangial cell fibronectin production was
      investigated. METHODS: Mesangial cells were exposed to 10 ng/ml of either TGF
      beta 1, TNF-alpha, or IL-1 beta or to TGF-beta 1 in combination with TNF-alpha or
      IL-1 beta. Tissue culture supernatants and cell lysates were assayed for
      fibronectin. Supernatants were also assayed for TGF-beta 1. Northern blot
      analyses probing for fibronectin, transin, TIMP-1 and TGF-beta 1 were carried out
      on RNA extracted from mesangial cells exposed to individual and combinations of
      cytokines. RESULTS: Individually these cytokines were only able to induce modest
      increases in fibronectin protein levels. However, when mesangial cells were
      exposed to TGF-beta 1 in combination with either TNF-alpha or IL-1 beta then
      fibronectin levels were synergistically up-regulated approximately fivefold over
      unstimulated levels. Northern analysis demonstrated that fibronectin mRNA levels
      in the combination were also synergistically increased. In contrast, rat transin
      gene expression in the combinations was reduced to well below levels induced by
      TNF-alpha and IL-1 beta individually. In addition, synergistic up-regulation of
      both TGF-beta 1 protein and message by the cytokine combinations was also
      observed. TGF-beta 1: TNF-alpha and TGF-beta 1: IL-1 beta induced additive
      increases in TIMP-1 (tissue inhibitor of metalloproteinases-1) mRNA levels.
      CONCLUSIONS: These data illustrate that complex interactions can occur between
      cytokines within the glomerulus modulating both matrix synthetic and degradation
      pathways. These could initiate the scarring process and the development of
      glomerulosclerosis.

PMID- 9648065
TI  - Interleukin (IL)-1 and IL-4 synergistically stimulate NF-IL6 activity and IL-6
      production in human mesangial cells.
AB  - BACKGROUND: While interleukin (IL)-4 inhibits pro-inflammatory cytokine
      expression by human monocytes, we have observed that it potentiates IL-6
      production by IL-1-activated human mesangial cells (MC). To study the mechanism
      of this cell-type specific interaction between IL-1 and IL-4 in MC, we examined
      the effect of both cytokines on the activities of nuclear factor kappa B (NF
      kappa B) and nuclear IL-6 NL-IL 6), transcription factors that are essential for
      IL-6 gene expression. METHODS: We evaluated IL-6 synthesis, mRNA expression, and
      mRNA stability by ELISA, Northern analysis, and the actinomycin D method,
      respectively. Activities of NF-kappa B and NF-IL 6 were analyzed by gel shift
      assay. RESULTS: IL-4 augmented the IL-1 stimulated IL-6 mRNA levels by about
      threefold without altering mRNA stability. IL-1 treatment rapidly induced the
      binding activity of NF-kappa B. In contrast, IL-4 did not affect basal and IL-1
      induced NF-kappa B activities. Both IL-1 and IL-4 stimulated NF-IL6 activity as
      early as 30 minutes after treatment. When MC were treated with both cytokines
      together, marked activation of NF-IL6 was observed at five hours. CONCLUSIONS:
      These results suggest that simultaneous activation of NF-kappa B and NF-IL6 is
      essential for IL-6 gene expression and that IL-1 and IL-4 cooperatively stimulate
      MC IL-6 production through their synergistic activation of NF-IL6.

PMID- 9648066
TI  - Regulation of cAMP production in initial and terminal inner medullary collecting
      ducts.
AB  - BACKGROUND: The inner medullary collecting duct (IMCD) is composed of at least
      two functionally and morphologically distinct segments, the initial (IMCDi) and
      the terminal (IMCDt) portions. However, most studies of receptor signaling have
      been performed on cells obtained from the entire inner medulla. The purpose of
      this study was to determine whether the patterns of receptor-activated cAMP
      accumulation were different between these segments. METHODS: We measured cAMP
      accumulation stimulated by vasopressin and isoproterenol, and the effect of
      epinephrine in freshly dissected IMCDi and IMCDt segments cultured and IMCDi and
      IMCDt cells in primary culture. RESULTS: The maximum response to vasopressin was
      twofold higher in fresh IMCDt verus IMCDi (P < 0.05), however, it increased in
      cultured IMCDi by 40% verus fresh cells with no change in the response in fresh
      verus cultured IMCDt. The maximum response to isoproterenol was small in fresh
      cells but increased by five- and sixfold, respectively, in cultured IMCDi and
      IMCDt cells. alpha 2-Adrenoceptor stimulation almost completely inhibited both
      vasopressin and isoproterenol-stimulated cAMP accumulations in fresh IMCDi and
      IMCDt cells, but only partially inhibited either accumulation by 34 to 49% in
      cultured cells. CONCLUSIONS: (1) IMCDi and IMCDt cells are both subject to
      vasopressin and alpha 2- and beta-adrenergic regulation of adenylyl cyclase
      activity; (2) the relative influence of beta-adrenergic, alpha 2-adrenergic and
      V2 receptors to affect cAMP accumulation is altered in primary culture versus
      freshly dissected IMCD segments, suggesting that caution must be exercised in the
      extrapolation of data from cultured IMCD cells to in vivo models.

PMID- 9648067
TI  - PAI-1 secretion and matrix deposition in human peritoneal mesothelial cell
      cultures: transcriptional regulation by TGF-beta 1.
AB  - BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1), the main inhibitor of
      plasminogen activators in plasma and in peritoneum, impairs plasmin formation
      that is essential for the repair processes of the mesothelium damaged by
      peritoneal dialysis fluids and peritonitis. The fibrogenetic cytokine
      transforming growth factor-beta (TGF-beta) displays variable effects on
      extracellular matrix remodeling enzymes and their inhibitors depending on tissues
      and cell lines. We previously found an unexpected stimulating effect of TGF-beta
      1 on matrix metalloproteinase-9 in peritoneal mesothelial cells. In this study,
      we analyzed the effects of TGF-beta 1 on PAI-1 production and deposition in
      extracellular matrix. METHODS: We used primary cultured mesothelial cells and a
      recently established human peritoneal mesothelial cell line (HMrSV5). Cell
      associated and secreted plasminogen activators and their inhibitors were detected
      and characterized by substrate gel zymography. PAI-1 was identified by reverse
      zymography and by Western blotting, and total PAI-1 was measured by ELISA.
      Secreted and cell-associated PA activity was measured by its ability to activate
      plasminogen into plasmin, that is, by the release of paranitroaniline from the
      plasmin synthetic substrate S-2251. PAI-1 mRNA accumulation was assessed by
      Northern blot. In vitro nuclear run-on assays were carried out to determine
      whether TGF-beta 1 had transcriptional effects on PAI-1 expression. Finally, the
      subcellular distribution of PAI-1 was analyzed by immunofluorescence and by
      immunogold silver staining. RESULTS: TGF-beta 1 increased PAI-1 antigen in the
      conditioned media of HMrSV5 cells, in a time- and concentration-dependent manner.
      This induced a dramatic decrease of free tPA in the cell medium and of membrane
      bound uPA, and a parallel increase of high molecular weight PA-PAI complexes.
      Consequently, secreted and cell-associated plasminogen activator activities were
      considerably reduced. In primary cultured peritoneal mesothelial cells, TGF-beta
      1 also induced PAI-1 secretion and the shift of tPA toward high molecular weight
      complexes. TGF-beta 1 increased PAI-1 mRNA in a time- and concentration-dependent
      manner. This effect was at least in part transcriptional since an approximately
      threefold increase in the rate of PAI-1 gene transcription was observed in nuclei
      sampled after a four-hour cell exposure to 5 ng/ml TGF-beta 1. Finally, TGF-beta
      1 substantially increased the amount of intracellular and matrix-associated PAI
      1. CONCLUSIONS: These results suggest that excessive TGF-beta 1 stimulated PAI-1
      could prevent appropriate peritoneal healing by impairing the degradation of
      fibrin and of unorganized matrix components, and by interfering with cell
      migration.

PMID- 9648068
TI  - Pirfenidone improves renal function and fibrosis in the post-obstructed kidney.
AB  - BACKGROUND: Pirfenidone (PFD) is a novel anti-fibrotic agent that can prevent and
      even reverse extracellular matrix accumulation in several organs, as shown by
      experimental and clinical studies. Unilateral ureteral obstruction (UUO) is a
      well-characterized model of experimental renal disease culminating in
      tubulointerstitial fibrosis. METHODS: UUO or sham-operated rats were administered
      PFD (500 mg/kg/day) in their food for 21 days to examine the effect on collagen
      production. The renal function was measured in the kidney after release of
      obstruction which had been maintained for one week to examine the effects of PFD
      on restoration after renal dysfunction. RESULTS: The collagen content detected by
      hydroxyproline progressively increased in kidney with UUO for 21 days. These
      increases were significantly suppressed by administration of PFD. PFD had no
      effect on collagen production in sham-operated rats. Expression of mRNA for type
      IV and I collagen and matrix metalloproteinase-2 in the cortex increased with
      UUO, but was inhibited by PFD treatment. The levels of cortical transforming
      growth factor-beta (TGF-beta) mRNA progressively rose with UUO for 21 days, but
      this increase also could be suppressed by PFD. Inulin clearance of the obstructed
      kidney was markedly depressed and remained low at five weeks after release. A
      progressive increase in hydroxyproline content was also observed in the post
      obstructed kidney despite the release of obstruction. Administration of PFD
      following the release not only attenuated collagen accumulation, but also induced
      recovery of the impaired renal function. CONCLUSIONS: These results demonstrate
      that PFD can attenuate both renal fibrosis and renal damage in this model, and
      suggest that PFD can be clinically useful for preventing progressive,
      irreversible renal failure.

PMID- 9648069
TI  - Up-regulation of HSP47 in the mouse kidneys with unilateral ureteral obstruction.
AB  - BACKGROUND: Unilateral ureteral obstruction (UUO) is a well established
      experimental model of renal injury leading to interstitial fibrosis. The
      molecular and cellular mechanism(s) of interstitial fibrosis in UUO are beginning
      to be elucidated. In the progression of interstitial fibrosis in UUO, up
      regulation of collagen synthesis is commonly observed. HSP47 is a collagen
      binding stress protein and is thought to be a collagen-specific molecular
      chaperone, which plays a pivotal role during the biosynthesis and secretion of
      collagen molecules in the endoplasmic reticulum. The synthesis of HSP47 has been
      demonstrated to always parallel that of collagen in physiological and
      pathophysiological conditions. It is well recognized that renin-angiotensin
      system (RAS) is enhanced in the setting of UUO and that enhanced RAS has been
      implicated in the pathogenesis of interstitial fibrosis in the obstructed
      kidneys. METHODS: To investigate the role of HSP47 in the progression of
      interstitial fibrosis in mouse UUO, the expression of HSP47 was examined by
      Northern blotting, immunohistochemistry and in situ hybridization in the
      obstructed kidneys. To test the possible involvement of enhanced RAS on the HSP47
      expression, we examined the effects of lisinopril, an angiotensin converting
      enzyme inhibitor, on interstitial fibrosis. HSP47 and type I collagen mRNA
      expression. RESULTS: By Northern blot analysis, HSP47 mRNA was significantly up
      regulated at 12 hours (about twice that of sham operated kidneys) after the onset
      of ureteral obstruction, further increased and stayed at the increased level
      until seven days (about 8 times that of sham operated kidneys). HSP47 mRNA and
      protein expression were observed in the periglomerular and peritubular
      interstitial regions of the obstructed kidneys. Distribution of smooth muscle
      alpha actin and type I collagen immunoreactivity were similar to the HSP47
      distribution pattern, suggesting that HSP47 was up-regulated in the
      myofibroblasts. Lisinopril ameliorated the expansion of cortical interstitium in
      the obstructed kidneys at four and seven days after ureteral obstruction. HSP47
      mRNA expression was suppressed at four and seven days, whereas type I collagen
      mRNA was suppressed only at seven days after the onset of ureteral obstruction.
      CONCLUSIONS: These results demonstrate the early and persistent up-regulation of
      HSP47 during the progression of interstitial fibrosis in mouse UUO kidneys, and
      further suggest the potential role of HSP47 in the pathogenesis of interstitial
      fibrosis in the obstructed kidneys. Partial suppression of HSP47 mRNA expression
      by lisinopril at day 4 and day 7 after ureteral obstruction suggests that there
      are other immediate trigger(s) that induce the HSP47 mRNA expression.
      Identification of the molecular mechanism of HSP47 induction during UUO may give
      an insight into the novel aspects of the molecular pathophysiology of
      interstitial fibrosis in obstructive nephropathy.

PMID- 9648070
TI  - Expression of decay accelerating factor mRNA and complement C3 mRNA in human
      diseased kidney.
AB  - BACKGROUND: Decay accelerating factor (DAF), a product of mesangial cells in
      vitro, is expressed on the surface of cells and is a candidate for the focal
      suppression of complement activation. It is not clear at present whether the
      levels of expression of DAF and intrarenal C3 synthesis correlate with the level
      of tissue injury. METHODS: Immunohistochemistry for DAF and C3 and nonradioactive
      in situ hybridization with digoxigenin-labeled oligonucleotide probe for DAF and
      C3 mRNA were performed in 22 tissue samples of kidneys from patients with IgA
      nephropathy (IgAN), 6 with membranous nephropathy (MN), 6 with lupus nephritis
      (LN), and five normal kidneys. RESULTS: In the normal kidney, DAF was confined to
      the juxtaglomerular apparatus and little or no C3 was detected; however, a few
      glomerular cells were positive for DAF mRNA but no C3 mRNA positive cells were
      detected. In diseased kidneys, DAF and C3 as well as their mRNAs were detected in
      mesangial cells, tubular cells and infiltrating cells. Glomerular epithelial
      cells and Bowman's capsule cells contained little or no DAF and C3 but were
      positive for their mRNAs. The mean percentages of mesangial cells positive for
      DAF and C3 mRNAs were 49.3 +/- 11.5% and 50.7 +/- 10.3% in IgAN, and 17.0 +/-
      6.3% and 19.4 +/- 9.0% in MN, respectively. The percentage of mesangial cells
      positive for DAF and C3 mRNAs among intraglomerular cells correlated positively
      with the degree of mesangial proliferation and glomerular sclerosis in IgAN. In
      contrast, in LN the percentage of glomerular cells positive for DAF mRNA
      correlated negatively with the degree of glomerular injury, while the percentage
      of cells positive for C3 mRNA did not change with the progression of the disease.
      The ratio of C3 mRNA/DAF mRNA of glomerular cells correlated with the degree of
      glomerular injury in both IgAN and LN. In the tubulointerstitium, the percentage
      of cells expressing mRNA, and C3 mRNA/DAF mRNA radio correlated with the degree
      of tubular atrophy and interstitial broadening in both IgAN and LN. CONCLUSIONS:
      We conclude that DAF and C3 mRNAs are synthesized in human diseased kidneys, and
      that a balance between locally synthesized DAF and C3 may be important in the
      progression of glomerulonephritis.

PMID- 9648071
TI  - Cloning of murine membrane-type-1-matrix metalloproteinase (MT-1-MMP) and its
      metanephric developmental regulation with respect to MMP-2 and its inhibitor.
AB  - BACKGROUND: Extracellular matrix macromolecules regulate morphogenesis of
      embryonic organs, and are developmentally regulated. Their expression and
      turnover is regulated by matrix metalloproteinases (MMPs). Recently, an
      epithelial cell "membrane" associated metalloproteinase (MT-1-MMP) has been
      identified that acts as an activator of a "secreted" MMP-2, and is produced by
      mesenchymal fibroblasts. The activity of MMP-2 is inhibited by a "soluble" tissue
      inhibitor of MMP-2, TIMP-2. The role of MT-1-MMP in renal development is unknown.
      METHODS: MT-1-MMP was cloned from embryonic mouse kidney cDNA library, and its
      spatio-temporal distribution during development in the context of MMP-2 and
      tissue inhibitor of metalloproteinase-2 (TIMP-2) was studied. RESULTS: The cloned
      MT-1-MMP exhibited approximately 86% nucleotide sequence homology with human MT-1
      MMP, and had a catalytic domain and a zinc binding site preceded by a RRKR furin
      recognition motif. A approximately 4.5 Kb MT-1-MMP mRNA transcript was detected,
      and its expression was developmentally regulated. A parallel developmental
      regulation of MMP-2 mRNA expression was also observed. TIMP-2 expression was also
      developmentally regulated, but lagged behind MT-1-MMP and MMP-2. By in situ
      hybridization, MT-1-MMP mRNA was seen to be confined to ureteric bud epithelia,
      and was absent in the mesenchyme, while MMP-2 was confined to the mesenchyme. MT
      1-MMP protein expression was seen on ureteric bud epithelia, induced mesenchyme
      and nascent nephrons, and it was highest during mid gestation. Similar spatio
      temporal expressions of MMP-2 and TIMP-2 proteins were observed. CONCLUSIONS:
      mRNAs of MT-MMP-1 and MMP-2 are expressed in the respective epithelial and
      mesenchymal compartments, while their proteins are co-expressed in the epithelia
      suggest that MT-1-MMP and MMP-2, in conjunction with TIMP-2, may be involved in
      paracrine/juxtacrine epithelial:mesenchymal interactions during
      metanephrogenesis.

PMID- 9648072
TI  - Local macrophage proliferation in human glomerulonephritis.
AB  - BACKGROUND: Local macrophage proliferation has been described in several animal
      models of glomerulonephritis (GN), but its significance in human disease is
      unknown. METHODS: Double immunostaining for CD68 and the proliferating cell
      nuclear antigen (PCNA) was used to identify macrophage proliferation in 84
      biopsies from a variety of glomerulonephridities. RESULTS: A small resident
      population of glomerular and interstitial CD68+ macrophages was identified in
      normal human kidney, of which only 1 to 2% showed evidence of proliferation on
      the basis of PCNA expression. A mild macrophage infiltrate, with only occasional
      proliferating macrophages, was seen in the less aggressive forms of GN (minimal
      change disease, non-IgA mesangioproliferative GN and IgA nephropathy). This was
      in sharp contrast to the more aggressive forms of disease (lupus class IV,
      vasculitis-associated GN, crescentic GN and mesangiocapillary proliferative GN),
      in which the prominent macrophage infiltrates contained many proliferating
      macrophages, accounting for 28 to 47% of the total macrophage population.
      Macrophage proliferation was largely restricted to areas of severe tissue damage
      (glomerular segmental proliferative lesions, crescents and foci of
      tubulointerstitial damage), suggesting that local proliferation is a mechanism
      for amplifying macrophage-mediated injury. Glomerular and interstitial macrophage
      proliferation gave a significant correlation with loss of renal function (P <
      0.0001) and histologic lesions (P < 0.0001), but not with proteinuria.
      Interstitial T-cell proliferation also gave a significant correlation with loss
      of renal function and histologic damage, even though proliferation within the T
      cell population was much lower than in the macrophage population. CONCLUSIONS:
      This study demonstrates that macrophage proliferation is a feature of the more
      aggressive forms of human GN. Local proliferation may be an important mechanism
      for amplifying macrophage-mediated renal injury. In addition, the degree of local
      macrophage proliferation may be a useful diagnostic and prognostic indicator for
      human GN.

PMID- 9648073
TI  - Characteristics of urea transport of cells derived from rabbit thick ascending
      limb of Henle's loop.
AB  - BACKGROUND: The thick ascending limb of Henle's loop (TALH) is thought to be
      involved in the regulation of the renal urea gradient. METHODS: We have
      characterized the uptake of urea (oil density centrifugation and 2-compartment
      culture) and volume regulation (impedance measurement) in highly differentiated
      cells derived from rabbit outer medulla. RESULTS: TALH cells exposed to 600
      mOsm/liter (300 mM urea) shrunk to 72 +/- 5% of the isoosmotic volume. Due to a
      regulatory volume increase (RVI), the cell volume was almost completely regained
      at 92 +/- 6% after five minutes. The uptake of 14C-urea in the presence of urea
      concentrations up to 600 mM did not show any saturation. In the presence of
      phloretin the urea uptake decreased to 69 +/- 14%. The transport was sodium and
      chloride independent. Changing the membrane potential caused an increase of
      regulatory volume increase and urea uptake. Hyperosmolarity induced by sucrose
      (300 mM) and NaCl (150 mM) caused a decrease of urea uptake to 70 +/- 14% and 53
      +/- 11%, respectively. The permeability coefficient (P) in a two compartment
      culture was P = 1.7 . 10(-6) +/- 0.39.10(-6) cm/second, suggesting a relatively
      low permeability. CONCLUSION: Due to the low permeability, it seems impossible to
      achieve a physiologically significant participation of the TALH in the urea
      circulation within the nephron. However, the results of this study provides
      significant hints about the existence of a specific urea transport mechanism that
      enables the cell to adapt rapidly to different osmolarities.

PMID- 9648074
TI  - Renal cortical mitochondrial aconitase is regulated in hypo- and hypercitraturia.
AB  - BACKGROUND: Chronic metabolic acidosis and K+ deficiency increase, while alkali
      feeding decreases proximal tubule citrate absorption and metabolism. The present
      studies examined the regulation of mitochondrial aconitase (m-aconitase), the
      first step in mitochondrial citrate metabolism, in these conditions. METHODS:
      Rats were fed appropriate diets, and m-aconitase activity and protein abundance
      measured. RESULTS: In chronic metabolic acidosis and chronic K+ deficiency, renal
      cortical m-aconitase activity was increased 17% and 43%, respectively. This was
      associated with respective 90% and 221% increases in renal cortical m-aconitase
      protein abundance. With chronic alkali feeding, there was a 12% decrease in renal
      cortical m-aconitase activity, associated with a 35% decrease in m-aconitase
      protein abundance. Hepatic m-aconitase activity was not regulated in a similar
      manner. There was no regulation of citrate synthase, the enzyme responsible for
      mitochondrial citrate synthesis. CONCLUSIONS: These studies demonstrate tissue
      specific chronic regulation of renal cortical m-aconitase activity and protein
      abundance, which likely contributes to the hypocitraturia and hypercitraturia
      seen in these conditions. As m-aconitase is the only step in citrate transport
      and metabolism found to be regulated in alkali feeding, its regulation likely
      plays a significant role in mediating the hypercitraturia seen in this condition.

PMID- 9648075
TI  - No net renal extraction of homocysteine in fasting humans.
AB  - BACKGROUND: The pathophysiological mechanism of hyperhomocysteinemia in chronic
      renal failure in humans is unknown. The loss of a putative renal homocysteine
      extraction in chronic renal failure has been hypothesized as significant
      homocysteine uptake has been demonstrated in the normal rat kidney. We studied
      homocysteine extraction in the normal human kidney. METHODS: We measured plasma
      total (free and protein-bound) and free homocysteine (tHcy and fHcy,
      respectively) in arterial and renal venous blood sampled from the aorta and right
      side renal vein during cardiac catheterization in 20 fasting patients with normal
      renal function. Renal homocysteine extraction was calculated as the arteriovenous
      difference divided by the arterial levels times 100%. RESULTS: No significant
      renal extraction was demonstrated either for tHcy: 0.9% (SD 5.8; 95% CI -1.8 to
      +3.6) or for fHcy: -0.2% (11.0; -5.4 to +4.9). CONCLUSIONS: We conclude that no
      significant net renal uptake of homocysteine occurs in fasting humans with normal
      renal function. The loss of such uptake, therefore, cannot cause
      hyperhomocysteinemia in patients with renal failure.

PMID- 9648076
TI  - Concentrating defect in experimental nephrotic syndrone: altered expression of
      aquaporins and thick ascending limb Na+ transporters.
AB  - BACKGROUND: Several pathophysiological states associated with deranged water
      balance are associated with altered expression and/or intracellular distribution
      of aquaporin water channels. The possible role of dysregulation of thick
      ascending limb NaCl transporters, which are responsible for countercurrent
      multiplication in the kidney, has not been evaluated. METHODS: Semiquantitative
      immunoblotting and immunocytochemistry were carried out in the kidneys of rat
      with adriamycin-induced nephrotic syndrome and in vehicle-injected control rats.
      RESULTS: Preliminary studies confirmed the presence of a severe concentrating
      defect. Semiquantitative immunoblotting of outer medullary homogenates
      demonstrated a marked decrease in the abundance of three thick ascending limb Na+
      transporters in nephrotic rats, namely the bumetanide-sensitive Na-K-2Cl
      cotransporter (BSC-1), the type 3 Na/H exchanger (NHE-3), and the alpha 1-subunit
      of the Na-K-ATPase. These results are predictive of a decrease in the NaCl
      transport capacity of the medullary thick ascending limb and therefore a decrease
      in countercurrent multiplication. Immunocytochemistry of outer medullary thin
      sections demonstrated broad (but highly variable) suppression of BSC-1 expression
      in the outer medullas of adriamycin-nephrotic rats. There was also a large
      decrease in outer medullary expression of two collecting duct water channels
      (aquaporin-2 and -3) and the major water channel of the thin descending limb of
      Henle's loop (aquaporin-1). CONCLUSION: The concentrating defect in adriamycin
      induced nephrotic syndrome in rats is a consequence of multiple defects in water
      and solute transporter expression, which would alter both the generation of
      medullary interstitial hypertonicity and osmotic equilibration in the collecting
      duct. Whether a similar widespread defect in transporter expression is present in
      idiopathic nephrotic syndrome is, at this point, untested.

PMID- 9648077
TI  - Low Na+ diet inhibits Na+ and water transport response to vasopressin in rat
      cortical collecting duct.
AB  - BACKGROUND: We previously demonstrated that vasopressin (AVP) produces a
      sustained increase in Na+ reabsorption by the isolated perfused cortical
      collecting duct (CCD) from rats on a normal diet, and that this effect is
      synergistic with that of pharmacological doses of deoxycorticosterone (DOC) or
      physiological levels of aldosterone. The present experiments examined the effect
      of AVP under the more physiological circumstances when plasma aldosterone was
      elevated by prior volume depletion. METHODS: Rats were volume depleted by a
      single dose of furosemide followed by a low-salt diet (0.3% NaCl) for four to
      nine days. Some of these rats were also implanted with a pellet containing 2.5 mg
      DOC. Rats in a third group were not injected with furosemide but were implanted
      with the DOC pellet and maintained on a standard (approximately 1% NaCl) diet.
      CCD were perfused and the lumen-to-bath Na+ flux (JNA), transepithelial voltage
      (VT), and osmotic water permeability (Pf) were measured in the presence and
      absence of 200 pm AVP. RESULTS: Although Na+ depletion by a single injection of
      furosemide and the low salt diet elevated plasma aldosterone and Vt, JNA remained
      low and there was a decreased response to AVP in comparison with DOC-treated rats
      on a standard diet. In CCD from rats on the low salt-diet with DOC, JNa was less
      than observed in CCD from DOC-treated rats on a standard diet. AVP-dependent Pf
      in CCD from rats on the low salt-diet, with or without DOC treatment, was also
      markedly lower. CONCLUSIONS: We interpret the results to demonstrate that maximal
      rates of Na+ reabsorption in the CCD depend not only on the synergistic
      stimulatory effects of aldosterone and AVP, but also require normal to high rates
      of salt delivery in vivo for the effects of the hormones on Na+ transport to be
      maximized in vitro.

PMID- 9648078
TI  - Role of endothelin and nitric oxide imbalance in the pathogenesis of hypoxia
      induced arterial hypertension.
AB  - BACKGROUND: We have recently demonstrated that prolonged hypobaric hypoxia can
      lead to a hematocrit-independent sustained arterial hypertension (HTN) in
      genetically normotensive Sprague-Dawley rats. The rise in blood pressure in the
      hypoxic animals was accompanied by a marked but transient increase in plasma
      endothelin level. In addition, hypoxia has been shown to decrease nitric oxide
      (NO) production by cultured endothelial cells. This study was designed to test
      the hypothesis that hypoxia-induced HTN may be mediated by increased endothelin
      and/or decreased NO production. METHODS: Blood pressure, plasma endothelin and
      urinary NO metabolites (NOx)were monitored in rats during a 24-hour exposure to
      hypobaric hypoxia (air pressure = 390 mm Hg). The results were compared with
      hypoxia (air pressure = 390 mm Hg). The results were compared with those obtained
      in animals maintained under normoxic condition (control group). To test the
      possible role of excess endothelin and depressed NO production, the studies were
      repeated using subgroups of animals treated with either an endothelin receptor ET
      A/B blocker (L-754,142) or L-arginine. RESULTS: The untreated hypoxic group
      exhibited a threefold rise in plasma endothelin and a threefold fall in urinary
      NOx, prior to the onset of HTN. Endothelin receptor blockade led to a further
      fall in urinary NOx excretion and failed to mitigate HTN. In contrast, L-arginine
      supplementation improved the urinary NOx excretion and prevented HTN. Neither
      therapy affected the hypoxia-induced erythrocytosis. CONCLUSIONS: We conclude
      that hypoxia-induced HTN is associated with depressed NO production and can be
      mitigated by L-arginine supplementation.

PMID- 9648079
TI  - Free pentosidine and neopterin as markers of progression rate in diabetic
      nephropathy. Collaborative Study Group.
AB  - BACKGROUND: Patients with diabetic nephropathy experience a progressive and
      usually inexorable decline in renal function. The presence of the structurally
      defined advanced glycation end product (AGE) pentosidine on tissue and
      circulating proteins has been correlated with the severity of diabetic
      complications. METHODS: To delineate a role for this AGE in the progression of
      diabetic nephropathy, glycohemoglobin and free and protein-bound pentosidine were
      measured in baseline stored serum and urine from a subgroup of patients with
      diabetes mellitus and proteinuria originally followed by the Collaborative Study
      Group Trial. To delineate a potential role for an immune-activation response to
      AGEs, the inflammatory markers, interleukin-6 (IL-6), C-reactive protein (CRP),
      and the monocyte activation marker marker neopterin were also measured at
      baseline. The patients chosen represented 67 subjects whose creatinine levels had
      "doubled" over the course of the study whether or not they later were treated
      with captopril, and 67 paired "non-doublers." RESULTS: Baseline disease activity,
      as manifested by glycohemoglobin, serum creatinine and degree of proteinuria was
      equal in the two groups, as was protein-bound pentosidine and the immune-markers
      IL-6 and CRP. At baseline the "doublers" as compared to the "non-doublers" had
      elevated serum levels of free pentosidine and neopterin. Baseline increases in
      these two parameters were also associated with an increased rate of "doubling" of
      serum creatinine by the proportional hazards method. CONCLUSION: Differences in
      individual responsiveness to AGEs, as manifested by either the production of free
      pentosidine or its release from a protein-bound form, and by evidence of
      monocyte/macrophage activation, are associated with progression of diabetic
      nephropathy.

PMID- 9648080
TI  - Serum homocysteine level and protein intake are related to risk of
      microalbuminuria: the Hoorn Study.
AB  - BACKGROUND: Microalbuminuria (MA) is a strong predictor of cardiovascular
      disease, but its causes are incompletely understood. Hyperhomocysteinemia is a
      recently recognized risk factor for cardiovascular disease independent of
      established risk factors. It is not known whether hyperhomocysteinemia is
      associated with MA, and thus could be a possible cause of microalbuminuria.
      METHODS: We studied an age-, sex- and glucose-tolerance-stratified random sample
      of a 50- to 75-year old general Caucasian population (N = 680). The urinary
      albumin-to-creatinine ratio (ACR) was measured in an early morning spot urine
      sample. MA was defined as an ACR > 3.0 mg/mmol. RESULTS: The prevalence of MA was
      4.3% (13 of 304) in subjects with normal glucose tolerance, 9.2% (17 of 185) in
      impaired glucose tolerance and 18.3% (30 of 164) in non-insulin-dependent
      diabetes mellitus (NIDDM); it was 3.7% (15 of 402) in subjects without
      hypertension and 17.9% (45 of 251) in those with hypertension. After adjusting
      for age, sex, glucose tolerance category, hypertension, dyslipidemia and smoking,
      the odds ratio [OR; 95% confidence interval (95%CI)] for MA per 5 mumol/liter
      total homocysteine increment was 1.33 (1.08 to 1.63). Additional adjustment for
      HbA1c, waist-hip ratio, protein intake and serum creatinine did not attenuate the
      association between MA and total homocysteine. A 0.1 g/kg.day increment of
      protein intake was also associated with an increased risk for MA after adjustment
      for age, sex, classical risk factors and serum total homocysteine [OR (95% CI);
      1.20 (1.08 to 1.32)]. CONCLUSION: Both hyperhomocysteinemia and protein intake
      are related to microalbuminuria independent of NIDDM and hypertension.
      Hyperhomocysteinemia may partly explain the link between MA and increased risk of
      cardiovascular disease.

PMID- 9648081
TI  - Effect of hyperparathyroidism on arterial distensibility in renal transplant
      recipients.
AB  - BACKGROUND: The cushioning function of the arterial system is altered in patients
      with end-stage renal failure. The role of hyperparathyroidism for the altered
      vessel wall properties of large arteries not known. METHODS: To exclude the
      confounding effects of fluid volume changes and hypercirculation as well as
      uremic toxicity on vessel wall properties from those of hyperparathyroidism, the
      present study was conducted in 54 normotensive renal transplant recipients with
      good graft function, three to six months after transplantation. The vessel wall
      properties of the common carotid artery were investigated in 32 of them, who had
      increased plasma intact parathyroid hormone (iPTH) levels (136 +/- 12 ng/liter,
      SEM), and compared to those of 22 control recipients of same age with normal
      plasma iPTH levels (34 +/- 4 ng/liter). Arterial distension was measured by
      Doppler analysis of the vessel wall movements, blood pressure was determined by
      sphygmomanometry. RESULTS: Blood pressure was 140 +/- 3/85 +/- 2 mm Hg in renal
      transplant recipients with hyperparathyroidism, 135 +/- 3/83 +/- 1 mm Hg in
      patients with normal plasma iPTH levels (NS). There was no difference in
      enddiastolic diameter of the common carotid artery (7.4 +/- 0.2 mm) in renal
      transplant recipients with hyperparathyroidism as compared with the control
      patients (7.3 +/- 0.2 mm; NS). Renal transplant recipients with
      hyperparathyroidism had a lower distension (389 +/- 27 microns vs. 486 +/- 28
      microns, P < 0.05) and distensibility coefficient of the common carotid artery
      (15.1 +/- 1.1 10(-3)/kPa vs. DC 19.0 +/- 1.0 10(-3)/kPa, P < 0.001) when compared
      with the control patients. Multiple regression analysis showed that the
      distensibility coefficient of the common carotid artery was negatively correlated
      with age (P < 0.001), mean arterial blood pressure (P < 0.05) and plasma iPTH
      levels (P < 0.05). The effects of plasma iPTH levels were not related to serum
      calcium concentrations or to differences in the enddiastolic diameter of the
      common carotid artery. CONCLUSIONS: The data suggest that secondary
      hyperparathyroidism can affect the cushioning function of larger arteries in
      patients with end-stage renal failure independently of high blood pressure.

PMID- 9648082
TI  - Cyclosporine suppresses rat hepatic cytochrome P450 in a time-dependent manner.
AB  - BACKGROUND: Cyclosporine is a potent immunosuppressant know to selectively
      suppress specific cytochrome P450 (P450) isoforms following chronic therapy in
      the rat. Cyclosporine undergoes significant hepatic metabolism in the rat,
      primarily due to P450 3A isoforms. Hence, alterations in hepatic metabolism of
      cyclosporine may lead to changes in drug pharmacokinetics or pharmacodynamics.
      The purpose of this study was to examine the temporal effect of chronic
      cyclosporine dosing on P450 protein expression and metabolic activity in a rat
      model of chronic cyclosporine nephropathy. METHODS: Adult male rats were
      administered cyclosporine 15 mg/kg/day or vehicle 1 ml/kg/day by subcutaneous
      injection for up to 28 days. To examine whether or not metabolic activity
      recovered following drug removal, additional rats were administered cyclosporine
      for 28 days followed by vehicle for up to an additional 15 days. Hepatic P450
      protein expression and microsomal metabolic activity were measured by Western
      blot analysis and in vitro steroid hydroxylation, respectively. RESULTS:
      Cyclosporine trough levels progressively increased over the 28 days period and
      were still measurable for up to 15 days after discontinuation. Immunoblot
      analysis indicated that chronic cyclosporine treatment suppressed P450 3A2
      expression and in vitro steroid hydroxylation in a time-dependent manner. Fifteen
      days following discontinuation of cyclosporine dosing, hepatic metabolic activity
      and microsomal P450 3A2 levels returned to near pre-dosing levels. CONCLUSIONS:
      We conclude that the time-dependent P450 suppression by cyclosporine may at least
      partially explain the variability in cyclosporine pharmacokinetics. These studies
      support the hypothesis that hepatic isoforms other than P450 3A2 may be
      responsible for cyclosporine metabolism during chronic treatment in the rat.

PMID- 9648083
TI  - Effect of alternative peritoneal dialysis solutions on cell viability,
      apoptosis/necrosis and cytokine expression in human monocytes.
AB  - BACKGROUND: Cellular function, cell viability and the cytokine network of human
      monocytes are influenced by the specific composition of peritoneal dialysis (PD)
      fluids. In an in vitro study using isolated human blood monocytes, we
      investigated the effect of peritoneal dialysates containing amino acids (Amino)
      or glucose polymer (Glu-poly) instead of glucose (Glu) as the osmotic agent, and
      bicarbonate (Bic) or PBS instead of lactate (Lac) as a buffer. METHODS: The
      following parameters were studied: mitochondrial dehydrogenase activity (using
      the MTT assay), interleukin (IL)-6 and IL-8 release (ELISA) and cellular IL-6
      mRNA expression after lipopolysaccharide (LPS) stimulation (using RT-PCR). FACS
      flow cytometry with annexin V and propidium iodide as markers and fluorescence
      microscopic methods were used to study the effects of the test fluids on cell
      necrosis and apoptosis. RESULTS: Glu/Lac pH 5.5 and Glu-poly/PBS pH 7.4 both
      significantly reduced mitochondrial dehydrogenase activity by more than 50% after
      60 minutes of incubation (30.5 +/- 7.6%, 42.5 +/- 6.5%, referred to RPMI 1640 as
      100%). Amino/Bic and Glu/Bic were both superior (Mtt assay > 63%). The rate of
      necrotic cells after 15 minutes of incubation measured by FACS was mostly
      increased with Glu/Lac pH 5.5 (29.9 +/- 4.0%). The rate of apoptotic cells,
      however, was not significantly different between the test solutions. The
      concentration of IL-6 in the supernatant of stimulated monocytes was highest with
      Glu/Bic (1023 +/- 278 pg/ml) and Amino/Bic (776 +/- 296 pg/ml) an lowest with
      Glu/lac pH 5.5 (46 +/- 22 pg/ml) and Glu-poly/PBS (32 +/- 13 pg/ml). IL-8 release
      from stimulated monocytes showed a similar pattern. Glu-poly/PBS showed a
      suppressive effect on IL-6 mRNA expression (ratio IL-6/beta-Actin, 0.4 +/- 0.25
      vs. RPMI 1.5 +/- 3.6). CONCLUSIONS: Bicarbonate buffered solutions both with
      glucose or amino acids as osmotic agents were superior when regarding cell
      metabolism, viability and cytokine release, while lactate buffered solutions and
      Glu-poly/PBS showed some reduced biocompatibility pattern for monocytes in vitro.

PMID- 9648084
TI  - Immunologic function and survival in hemodialysis patients.
AB  - BACKGROUND: Although the medical determinants of mortality in patients with end
      stage renal disease (ESRD) treated with hemodialysis (HD) are well appreciated,
      the contribution of immunologic parameters to survival in such patients is
      unclear, especially when variations in age, medical comorbidity and nutrition are
      controlled. In addition, although dysregulation of cytokine metabolism has been
      appreciated in patients with ESRD, the association of these parameters with
      outcomes has not been established. Recently, the type of dialyzer used in
      patients' treatment has been associated with survival, but the mechanisms
      underlying these findings, including their immune effects, have not been
      established. We conducted a prospective, cross-sectional, observational
      multicenter study of urban HD patients to determine the contribution of
      immunological factors to patient survival. We hypothesized increased
      proinflammatory cytokines would be associated with increased mortality, and that
      improved immune function would be associated with survival. METHODS: Patients
      were assessed using demographic and anthropometric indices, Kt/V, protein
      catabolic rate (PCR) and immunologic variables including circulating cytokine
      [interleukin (IL)-1, IL-2, IL-4, IL-5, IL-6, IL-12, IL-13 and tumor necrosis
      factor (TNF)-alpha] levels, total hemolytic complement activity (CH50), and T
      cell number and function. A severity index, previously demonstrated to be a
      mortality marker, was used to grade medical comorbidity. A Cox proportional
      hazards model, controlling for patients' age, severity index, level of serum
      albumin concentration, dialyzer type and dialysis site was used to asses relative
      survival risk. RESULTS: Two hundred and thirty patients entered the study. The
      mean (+/- SD) age of the population was 54.4 +/- 14.2 years, mean serum albumin
      concentration was 3.86 +/- 0.47 g/dl, mean PCR was 1.1 +/- 0.28 g/kg/day, and
      mean Kt/V 1.2 +/- 0.3. Patients' serum albumin concentration was correlated with
      levels of Kt/V and PCR, and their circulating IL-13 and TNF-alpha levels, but
      negatively with their circulating IL-2 levels, T-cell number and T-cell antigen
      recall function. T-cell antigen recall function correlated negatively with PCR,
      but not Kt/V. There was no correlation of any other immune parameter and medical
      or demographic factor. Immune parameters, were all highly intercorrelated. Mean
      level of circulating cytokines in HD patients were in all cases greater than
      those of a normal control group. There were few differences in medical risk
      factors or immune parameters between patients treated with different types of
      dialyzers. After an almost three-year mean follow-up period, increased IL-1, TNF
      alpha, IL-6, and IL-13 levels were significantly associated with increased
      relative mortality risk, while higher levels of IL-2, IL-4, IL-5, IL-12, T-cell
      number and function, and CH50 were associated with improved survival. The
      difference in survival between patients treated with unmodified cellulose
      dialyzers and modified or synthetic dialyzers approached the level of statistical
      significance, but there were no differences in levels of circulating cytokines
      between these two groups. CONCLUSIONS: Higher levels of circulating
      proinflammatory cytokines are associated with mortality, while immune parameters
      reflecting improved T-cell function are associated with survival in ESRD patients
      treated with HD, independent of other medical risk factors. These factors may
      serve as markers for outcome. The mechanism underlying the relationship of immune
      function and survival, and the effect of interventions to normalize immune
      function in HD patients should be studied.

PMID- 9648085
TI  - Psychosocial factors, behavioral compliance and survival in urban hemodialysis
      patients.
AB  - BACKGROUND: The medical risk factors associated with increased mortality in
      hemodialysis (HD) patients are well known, but the psychosocial factors that may
      affect outcome have not been clearly defined. Psychosocial factors could affect
      mortality through interaction with parents' nutrition or their compliance with
      the dialysis prescription. We conducted a prospective, longitudinal, multicenter
      study of urban HD patients to determine the contribution of compliance and
      psychosocial factors to patient survival. METHODS: Patients were assessed using
      indices of social support, patient's assessments of their well-being, including
      illness effects (IEQ), and satisfaction with life (SWLS), the Beck Depression
      Inventory (BDI), serum albumin concentration, Kt/V and protein catabolic rate
      (PCR). Behavioral compliance was measured three ways: percent time actually
      dialyzed per treatment compared to prescribed time (shortening behavior); percent
      sessions attended (skipping behavior) and total integrated time compliance (%
      TCOMP). A severity index, previously demonstrated to be a mortality marker, was
      used to grade medical comorbidity. The typed of dialyzer the patient was treated
      with was noted. A Cox proportional hazards model, controlling for age, medical
      comorbidity, albumin concentration and dialyzer type was used to assess relative
      mortality risk of variations in psychosocial factors and behavioral compliance.
      RESULTS: A total of 295 patients (60.8% of those eligible) agreed to participate.
      The mean ( +/- SD) age of our population was 54.6 +/- 14.1 year, mean PCR was
      1.06 +/- 0.27 g/kg/day, and mean Kt/V 1.2 +/- 0.4, suggesting the patients were
      well nourished and adequately dialyzed. The patients' mean BDI was 11.4 +/- 8.1
      (in the range of mild depression). Patients' SWLS was similar to that of a group
      of patients without chronic illness. After a 26 month mean follow-up period,
      higher levels of perceived social support, improved perception of the effects of
      illness and increased behavioral compliance were significantly associated with
      decreased relative mortality risk (0.8, 0.77, and 0.79, respectively), controlled
      for variations in patients' age, severity of illness, serum albumin concentration
      and dialyzer type. Variations in depression and Kt/V were not predictors of
      mortality during the observation period. CONCLUSIONS: Lower levels of social
      support, decreased behavioral compliance with the dialysis prescription, and
      increased negative perception of the effects of illness are independently
      associated with increased mortality in ESRD patients treated with HD. The effects
      are of the same order of magnitude as medical risk factors. Such effects may be
      attributable to a relationship between a patients' perception of social support
      and effects of illness and behavior, with other factors such as the provision of
      better medical care in patients with larger social networks. The mechanism
      underlying the relationship of psychosocial factors and compliance and survival,
      and the effect of interventions to improve perception of illness, and increase
      social support and compliance with the dialysis prescription in HD patients
      should be studied.

PMID- 9648086
TI  - Diagnostic accuracy and prognostic value of combined dipyridamole-exercise
      thallium imaging in hemodialysis patients.
AB  - BACKGROUND: Non-invasive detection of coronary artery disease in dialysis
      patients, a major cause of mortality, often remains difficult. The aim of the
      study was to test the diagnostic and prognostic accuracies of combined
      dipyridamole-exercise thallium imaging in dialysis patients. METHODS:
      Dipyridamole-exercise thallium imaging and coronary angiography were both
      performed prospectively in 60 asymptomatic hemodialysis patients who were
      followed up, long term, by recording any major coronary event. RESULTS: Coronary
      angiography was abnormal in 13 patients (21%), and there was abnormal thallium
      uptake in 17 patients. Sensitivity, specificity, positive and negative predictive
      values, and overall accuracy of thallium to detect a coronary artery disease were
      92, 89, 71, 98 and 90%, respectively. After a median follow-up of 2.8 years, 12
      patients experienced at least one major coronary event (4 cardiac deaths, 5
      myocardial infarctions and 3 revascularizations). Eight of the 17 patients with
      abnormal thallium uptake (47%) suffered a coronary event, compared to only 4 of
      the 43 patients (9%) with a normal thallium uptake (P < 0.001). The positive
      prognostic predictive value of thallium imaging was 47% and its negative
      predictive value was 91%. The probability of survival free of coronary events was
      significantly higher in patients with normal thallium uptake than in those with
      abnormal thallium uptake (crude risk ratio 7.6; P < 0.001) even after adjustment
      for several risk factors for cardiovascular disease (adjusted risk ratio 9.2; P <
      0.005). CONCLUSION: In dialysis patients, combined dipyridamole-exercise thallium
      imaging is an accurate method for detecting coronary stenosis and for predicting
      future coronary events.

PMID- 9648087
TI  - On-line assessment of delivered dialysis dose.
AB  - BACKGROUND: The adequacy of the delivered dialysis dose is essential to prevent
      patient morbidity and mortality. The determination of effective ionic dialysance
      (D) is easy, non-invasive and inexpensive, and its use instead of effective urea
      clearance (K) in kinetically determining apparent" urea distribution volume (Vt)
      is likely to lead to a correct Kt/V, even though the Vt value may be incorrect.
      The aim of this study was to test the possibility of using the measurement of D
      to monitor Kt/V on-line during each dialysis treatment. METHODS: Forty-four
      patients were dialyzed using a monitor equipped with specially designed "Diascan
      Module" (COT; Hospal) that measures effective D by means of a single conductivity
      probe. Vt was calculated according to the SPVV three BUN method urea kinetic
      model using D instead of K values. One month later, Kt/V was calculated as Dt/V,
      using actual D and T values and the predetermined Vt values updated for the
      current final body wt. Both the Dt/V and Kt/V determined according to the Smye
      and Daugirdas methods were compared with the Kt/V determined using the SPVV
      kinetic model (Kt/Veq) RESULTS: The Kt/V values calculated using ionic dialysance
      and predetermined Vt were approximately equivalent to those of Kt/Veq (1.14 +/-
      0.16 vs. 1.14 +/- 0.17, mean difference 0.00 +/- 0.07), as were those determined
      according to the Smye and Daugirdas methods (1.10 +/- 0.18 and 1.13 +/- 0.17,
      mean difference -0.03 +/- 0.06 and 0.01 +/- 0.06, respectively). CONCLUSION: Once
      Vt has been determined, the evaluation of ionic dialysance in stable patients
      makes it possible to calculate the Kt/V accurately at each dialysis session
      without blood or dialysate sampling, and at no additional cost.

PMID- 9648088
TI  - The acu-men: a new device for continuous renal replacement therapy in acute renal
      failure.
AB  - BACKGROUND: We sought to design a simple machine to safely provide continuous
      veno-venous hemofiltration to acute renal failure patients. RESULTS: The acu-men
      device uses a pneumatic blood pump with tidal blood flow as the driving force. A
      volumetric balancing system balances the filtrate with the replacement fluid, and
      the blood-air interface is eliminated by replacing the conventional venous drip
      chamber with two air-separating membranes. The extracorporeal circuit is
      integrated in a disposable cartridge, which is inserted into the machine at the
      beginning of treatment. The priming and rinsing is done automatically.
      CONCLUSION: While preliminary data from an ongoing clinic trial on the efficacy
      of the device are encouraging, further long-term studies are necessary to
      evaluate its potential to decrease morbidity and mortality in acute renal failure
      patients.

PMID- 9648089
TI  - A simple procedure for the isolation of rat kidney lysosomes.
AB  - BACKGROUND: A procedure for the isolation of highly purified lysosomes from
      normal rat kidney is described. METHODS: The method depends on the swelling of
      mitochondria when the postnuclear supernatant fraction is incubated with 2 mM
      Ca2+. The lysosomes can then be separated from the swollen mitochondria by
      Percoll density gradient centrifugation. RESULTS: The lysosomal fraction obtained
      by our method was enriched more than 30-fold in terms of marker enzymes with a
      yield of about 11%. Electron microscopic examination and the measurement of the
      activities of marker enzymes for various subcellular organelles indicated that
      our lysosomal preparation was essentially free from contamination by other
      organelles. CONCLUSION: We believe that this procedure for isolating kidney
      lysosome will be useful in the study of the mechanisms of specific modification,
      processing and catabolism of proteins.

PMID- 9648090
TI  - Mutational analysis of patients with cystinuria detected by a genetic screening
      network: powerful tools in understanding the several forms of the disorder.

PMID- 9648091
TI  - From microalbuminuria to hyperhomocysteinemia.

PMID- 9648092
TI  - Dialysis fluids and monocytes: suicide or murder?

PMID- 9648093
TI  - Obstructive nephropathy.

PMID- 9648095
TI  - Does occupational exposure to toxins increase albumin excretion rate?

PMID- 9648094
TI  - Re: Kitamura et al: "Inhibition of myo-inositol transport causes acute renal
      failure with selective medullary injury in the rat".

PMID- 9648096
TI  - Animal cell culture equipment and techniques.

PMID- 9648097
TI  - Making informed choices: medium, serum, and serum-free medium. How to choose the
      appropriate medium and culture system for the model you wish to create.
AB  - Complex nutrient mixtures, which are usually called "media," are almost always
      supplemented with serum, with another complex biological fluid (e.g., milk,
      embryo extracts, and plasma), or with a defined mixture of hormones and growth
      factors. The choice of medium and supplements can have a major impact on the
      growth, function, and even phenotypic and genetic stability of cells in vitro.
      This choice thus becomes an important part of developing a useful and meaningful
      in vitro model system. This chapter defines the various roles that the medium
      plays in supporting cell function and outlines a method for selecting and
      optimizing medium in growing the cell of choice.

PMID- 9648098
TI  - Cell line availability: where to get the cell lines you need.
AB  - The availability and utility of cell lines with limited and continuous doubling
      potential are summarized and documented. Reference to national cell banks is
      included with pertinent and current contact information. The continuing need for
      vigorous application of quality control procedures is emphasized with data
      illustrating frequencies of microbial infection in cultured cell lines as well as
      high incidences of cross-contamination of one cell line with another.

PMID- 9648099
TI  - Cell culture contamination: sources, consequences, prevention, and elimination.
AB  - The subject of the chapter is cell culture contamination. Contamination may enter
      the cell culture system as a physical, chemical, and/or biological component of
      the environment. The potential sources and consequences of cell culture
      contamination are unique to the cell culture system and the contaminant. A basic
      understanding of cell culture contamination is necessary to appreciate the need
      to develop and practice standardized cell culture procedures. General sources,
      consequences, and preventative measures are discussed for physical and chemical
      contamination based on current technology. Mycoplasmal contamination is the focus
      of the discussion on biological contamination and its impact on cell cultures.
      The introduction of other biological contaminants should be controlled by the
      institution of cell culture management procedures needed to minimize the
      incidence of mycoplasmal contamination. The need to eliminate the routine use of
      antibiotics in cell culture systems and institute routine testing to detect
      contamination is emphasized. More rapid detection of contamination should reduce
      the incidence of cross-contamination and minimize the consequences of any
      contamination event.

PMID- 9648100
TI  - Immortalization by gene transfection.
AB  - Cultured cell lines that maintain specific differentiated phenotypes have been
      indispensable tools in cell biology. Progress in understanding the function of
      differentiated cells in vivo can be facilitated by creating cell lines via
      immortalizing gene transduction, if they retain the essential differentiated
      features of the same cells in vivo. Rodent cells immortalize spontaneously with a
      frequency of 10(-5) to 10(-6). Thus, it is easy to isolate immortal cells from
      rodent cell populations even without the transfer of immortalizing genes.
      Immortalizing genes can be used to increase this frequency to approximately 100%.
      In contrast, the spontaneous immortalization of human cells is a very rare event;
      the frequency is thought to be < 10(-12). Immortalizing genes can also be used to
      increase this frequency. Several genes that promise efficient immortalization of
      cultured cells have been identified. Immortalizing genes include simian virus 40
      large T antigen, papillomaviruses E6 and E7, adenovirus E1A, Epstein-Barr virus,
      human T-cell leukemia virus, herpesvirus saimiri, oncogenes, and mutant p53 gene.
      Equally important, innovative means of gene delivery have been developed as well.
      These immortalizing genes, together with gene transfer methodologies, have
      provided the means to generate cell lines from cell types that are not abundant
      or are difficult to obtain in pure form in primary culture, are in short supply
      as human cells, and/or have brief lifetimes in culture. This chapter focuses
      primarily on the immortalization method by gene transfection. The chapter is not
      meant to be comprehensive, but rather to provide an account of the power and
      usefulness of immortalization methodology.

PMID- 9648101
TI  - Establishment of mammalian testicular cell lines.

PMID- 9648102
TI  - Cell hybridization, hybridomas, and human hybridomas.
AB  - Cell hybridization is one of the most basic cytotechnologies. The
      hemagglutinating virus of Japan was first used to cause cell fusion; however,
      polyethylene glycol is widely used now because of simplicity of procedure. This
      chapter first explains the principles of cell hybridization methods and then
      describes the practical protocols for preparing mouse hybridomas using
      polyethylene glycol. So far, lack of an excellent human fusion partner cell line
      that has high fusion efficiencies and does not produce immunoglobulin has
      hindered the spread of human-human hybridoma preparation methods. In the authors'
      laboratory NAT-30 and HO-323, human parent cell lines with high fusion
      efficiencies, have been established to prepare many hybridoma cell lines
      producing cancer-specific human monoclonal antibodies. Because NAT-30 and HO-323
      cell lines are IgM producers, it is difficult to obtain IgG-producing hybridomas
      because the types of immunoglobulin produced by hybridomas are strongly affected
      by the characteristics of parent cells. Thus a nonimmunoglobulin-producing human
      parent cell line, A4H12, derived from human T lymphoma was established that can
      efficiently obtain IgG-producing human hybridomas. Another problem with preparing
      human hybridomas is that it is difficult to obtain B lymphocytes immunized with
      optional antigens for ethical reasons. To overcome this problem, in vitro
      immunization methods have been developed that allow exposure of a large number of
      B lymphocytes to cultured cancer cell or soluble antigens. The section on human
      hybridomas explains human fusion partners, in vitro immunization methods, and the
      preparation of human-human hybridomas using an electrofusion method. Finally, the
      application of human monoclonal antibodies to medical uses and the preparation of
      supranatural monoclonal antibodies are reviewed. These include multifunctional
      monoclonal antibodies and altered monoclonal antibodies having increased affinity
      and specificity by exchanging or modifying light chains.

PMID- 9648103
TI  - Establishing human glioma-derived cell lines.

PMID- 9648104
TI  - Culture methods for selective growth of normal rat and human Schwann cells.
AB  - Beginning with an introduction of the Schwann cell itself, this chapter provides
      detailed methodology for growing pure Schwann cells of rat and human origin in
      serum-free medium without complicated cell purification schemes. Section II lists
      the essential preexperiment preparations such as materials, instruments, tissue
      culture medium, and solutions. Section III begins with the procedure for the
      dissection of embryonic dorsal root ganglia (DRG) from E14-E15 rat embryos,
      neonatal rats, and adult rats with diagrams; methods for enzymatic dissociation
      of the DRGs and the initiation of primary culture follow. A description of
      primary cultures with photographs is also provided for comparison. This section
      ends with a protocol for and results expected of serial passaging of rat Schwann
      cells. Section IV carefully describes the culture of Schwann cells from human
      adult nerve biopsy, a procedure that produces a thousandfold expansion of human
      Schwann cells within a month from initial plating. In the last section, basic
      immunocytochemistry as well as advanced in vitro remyelination techniques are
      provided for biochemical and functional characterization of Schwann cell
      cultures.

PMID- 9648105
TI  - Invertebrate cell culture considerations: insects, ticks, shellfish, and worms.
AB  - Establishment of cell lines from insect and arachnid invertebrates has become
      routine, whereas other invertebrate taxa have been frustratingly unproductive of
      cell lines. None is available for any marine invertebrate, despite a strong and
      well-recognized need for cell lines from species that are important in
      aquaculture, from parasite vectors and intermediate hosts of parasites, from
      parasites themselves, from certain biomedical models, and from other species that
      are pests. Drawing on experiences gained attempting to establish cell lines from
      molluscs and trematodes and on published and ongoing research with diverse
      invertebrates, this chapter attempts to anticipate the problems that are likely
      to be encountered in such endeavors and discusses possible solutions. Criteria to
      be considered in the selection of basic culture media, temperature, pH, and media
      additives; approaches that have been developed to yield sterile primary cultures;
      and factors to consider in decisions about feeding schedules, retention of tissue
      fragments and nonadherent cells, use of heterologous feeder layers, and other
      variables are described. Suggestions are made concerning means to objectively
      score the success of tested variables and means to induce cell replication. The
      chapter ends with notes on conventional means to characterize cell lines and an
      account of contemporary efforts to immortalize cells by means of genome
      manipulation. Enduring success with a single molluscan cell line, transient
      successes with crustacean and helminth cell lines, and promising developments in
      transgenesis with invertebrates all lead to the hopeful conclusion that the
      invisible barrier to cell propagation in historically refractory species will
      soon be a thing of the past.

PMID- 9648106
TI  - Cell line characterization and authentication.
AB  - Research and development involving the use of cell lines require precise
      knowledge of the purity and species of origin of the cell lines used. This can
      only be assured by periodic monitoring of cultured cell lines for possible
      contamination by other cells and for characteristics that authenticate the cell
      line identity. In the absence of such monitoring, inter- and intraspecies cell
      line contaminations are likely to occur in the laboratories of unsuspecting
      investigators and can result in the generation of mistaken conclusions with an
      attendant loss of investigators' time, effort, and resources. This chapter
      provides a history and an overview of the methods that have been developed for
      cell line authentication, the type of information each of these different methods
      provides, and how synthesis of that information can be used to characterize a
      cell line and confirm its identity. An effective cell line monitoring strategy is
      described that involves testing for a combination of genetic markers, including
      cell membrane species antigens, isoenzymes, chromosomes, and DNA fingerprints,
      and use of databases for each marker system to compare the results obtained with
      a test cell culture with results from an extensive panel of previously tested
      cell lines.

PMID- 9648107
TI  - Laboratory scaleup of cell cultures (0.5-50 liters).
AB  - With the modern tools of molecular and cell biology now available, many
      researchers find the need to scale up cell culture in order to produce large
      quantities of cells or conditioned medium for the further purification of
      proteins or subcellular fractions. The method used for scaleup will depend on the
      properties of the cell being used, the amount of material desired, the number of
      times the process is to be run, and the resources available. Roller bottles,
      microcarrier cultures, and hollow fiber cultures provide appropriate and
      scaleable growth systems for attachment-dependent cells. However, the most
      efficient production of material, especially if the large-scale production is to
      be repeated several times, is obtained by suspension adapting the cells and
      growing them in suspension. This can be done in spinners or in fermenters, which
      range in size from 0.1 to 12,000 liters in volume. This chapter describes methods
      for choosing the optimal production system and medium for scaling up to different
      levels of production and for suspension adapting cells for scaleup of suspension
      culture.

PMID- 9648108
TI  - Cell synchronization.
AB  - This chapter describes methods for analyzing the cell cycle kinetics of
      asynchronous mammalian cells and for preparing synchronous cultures. The
      described asynchronous cell methods include determination of mean generation time
      and proliferative fraction, determination of mitotic and [3H]thymidine-labeling
      indices, and estimation of cell cycle phase durations by the labeled mitoses
      procedure and by flow cytometry. The described synchronization methods include
      release from G0 arrest, release from M-phase and S-phase blocking agents, mitotic
      detachment, and centrifugal elutriation. Caveats in interpreting cell synchrony
      experiments are discussed.

PMID- 9648109
TI  - Measurement of cell death.
AB  - Apoptosis, or programmed cell death, is a physiological form of cell death that
      plays a critical role in the development and maintenance of multicellular
      organisms. Apoptosis is characterized based on morphological and biochemical
      criteria. Morphological characteristics include cell shrinkage, cytoplasmic
      condensation, chromatin segregation and condensation, membrane blebbing, and the
      formation of membrane-bound apoptotic bodies, whereas the biochemical hallmark of
      apoptosis is internucleosomal DNA cleavage into oligonucleosome-length fragments.
      A great deal of research is aimed at defining the molecular mechanisms that play
      a role in apoptosis. As one of the common end points of experiments related to
      apoptosis is in fact the death of the cell, it has become important to develop
      reliable assays to measure cell death that may be compared among the various
      systems being investigated. This chapter reviews many of the current methods used
      to measure apoptotic cell death and points out strengths and weaknesses of each
      approach with respect to the system being examined and the questions being asked.
      Traditional cell-based methods, including light and electron microscopy, vital
      dyes, and nuclear stains, are described. Biochemical methods such as DNA
      laddering, lactate dehydrogenase enzyme release, and MTT/XTT enzyme activity are
      described as well. Additionally, terminal deoxynucleotidyl transferase-mediated
      dUTP-biotin nick end labeling of DNA fragments (TUNEL) and in situ end labeling
      (ISEL) techniques are reviewed, which when used in conjunction with standard flow
      cytometric staining methods may yield informative data relating cell death to
      various cellular parameters, including cell cycle and cell phenotype. The use of
      one or more of the methods described in this chapter for measuring cell death
      should enable investigators to accurately assess apoptosis in the context of the
      various models being examined and help define causal relationships between the
      mechanisms that regulate apoptosis and the cell death event itself.

PMID- 9648110
TI  - Simultaneous measurement of cell cycle and apoptotic cell death.
AB  - Understanding the dynamics of cell death in conjunction with those of cell cycle
      can be illuminating in the investigation of various cellular behaviors. Robust
      assays for measuring such parameters are invaluable. Many assays of apoptosis
      and/or cell cycle use flow cytometry. This chapter describes two different assays
      to measure apoptosis and cell cycle simultaneously using flow cytometry. The
      first involves the use of terminal transferase (the "TUNEL" assay) together with
      propidium iodide for identification of cell cycle. The second uses fluorescently
      labeled annexin V, together with propidium iodide as an indicator of cell
      membrane integrity; and additionally Hoechst 33342 for determination of cell
      cycle. Each assay has positive and negative attributes. The terminal transferase
      assay is performed using fixed cells and is therefore useful in the analysis of
      samples collected over time. The annexin V assay is performed using unfixed
      cells, and thus provides information regarding membrane integrity. Other
      practical aspects of both assays are discussed.

PMID- 9648111
TI  - Embryonic stem cells, creating transgenic animals.
AB  - Embryonic stem (ES) cells have afforded a means of directly modifying the mouse
      genome in vitro and then introducing such changes directly into animals. The
      advent of this technology has made the mouse the mammal of choice for mutagenesis
      approaches used in the study of embryonic development and disease conditions.
      This chapter deals with the maintenance and modification of these pluripotent
      cell lines and describes the routes that can be taken for their efficient
      introduction to the in vivo environment.

PMID- 9648112
TI  - Electron microscopy: use of transmission and scanning electron microscopy to
      study cells in culture.
AB  - Standard techniques for electron microscopy were developed for tissues dissected
      from animals. Optimal methods for electron microscopy of cells in culture are
      different. This chapter describes methods for processing cells grown on plastic
      or in suspension. Both transmission and scanning electron microscopy are
      discussed. The focus is on the procedures for fixation, dehydration, embedding,
      and staining, which will help the reader to obtain superior electron micrographs
      of cultured cells.

PMID- 9648113
TI  - Indirect immunofluorescence microscopy in cultured cells.
AB  - The technique of fluorescence immunolocalization has evolved steadily since its
      first application in the mid-1960s, incorporating innovations in probe chemistry,
      microscopy, and image detection. This chapter provides an overview of the current
      status of indirect immunofluorescence for those starting to use the method. It
      includes both general considerations from cell culture to image detection and
      several protocols that should serve as an entry point for this technique.

PMID- 9648114
TI  - Cellular localization of mRNA and protein: in situ hybridization histochemistry
      and in situ ligand binding.
AB  - Powerful methods for the detection of mRNA and proteins in cells and tissue
      sections have been developed since the mid-1980s. This chapter discusses the
      applications of in situ hybridization histochemistry and in situ ligand binding
      to cells in culture and tissue sections. In situ hybridization takes advantage of
      paired nucleotide interactions between a labeled probe (antisense strand) and the
      endogenous mRNA (sense strand). Following processing, the mRNA is localized
      through detection of the disintegration pattern of the radiolabeled probe.
      Protein-protein interaction is detected in a similar fashion. Proteins are
      radiolabeled and incubated with tissues that contain target-binding proteins or
      receptors. On processing, the interaction sites are localized through detection
      of the radiolabeled probe. The methods are rapid, sensitive, specific, and
      provide important information regarding the sites of mRNA synthesis, abundance of
      protein, and the ability of the ligand to interact with the receptor in
      restricted cellular populations. Application of these techniques to cells in
      culture allows in vitro manipulation of endogenous mRNA or protein with various
      hormones or growth factors and a method to detect the results.

PMID- 9648115
TI  - Epidemic neuropathy in Cuba: a public health problem related to the Cuban
      Democracy Act of the United States.
AB  - In 1992, the USA embargo on Cuba was tightened through the passage of the Cuban
      Democracy Act (CDA) that explicitly restricts food and medical supplies. The
      embargo has contributed to cause a number of public health problems in Cuba
      including: (1) an epidemic of more than 50,000 cases of optic and peripheral
      neuropathies in 1992-1993, resulting from dietary deficiency; (2) an epidemic of
      esophageal stenoses in toddlers who inadvertently drank liquid lye as a result of
      a soap shortage for which liquid lye was substituted; (3) an outbreak of Guillain
      Barre syndrome in Havana, in June and July 1994, resulting from water
      contamination due to lack of chemicals for water treatment to eliminate
      Campylobacter sp.; (4) outbreaks of self-inflicted disease and injuries caused by
      rioting among Cubans detained at the US Naval base at Guantanamo Bay, and (5) a
      decline in medical practice standards and public health indicators in Cuba
      resulting from the enactment of the CDA, documented by the American Public Health
      Association in 1993 and confirmed in March 1997 by the American Association for
      World Health. Despite this evidence, the Cuban embargo remains a politically
      sensitive subject in the USA, resistant to public health concerns, as evidenced
      by the recent passage of the Helms-Burton Act. The public health effects of the
      CDA need to be reviewed with possible revocation or at least modification.

PMID- 9648116
TI  - Health-related quality of life outcomes in stroke.

PMID- 9648117
TI  - Epidemiology of stroke in The Netherlands from 1972 to 1994: the end of the
      decline in stroke mortality.
AB  - In 1994, stroke was responsible for the death of 4,994 men and 7,601 women in the
      Netherlands, corresponding to 7.5% of all deaths in men and 11.4% in women. Age
      adjusted stroke mortality declined by 39% for men and by 45% for women between
      1972 and 1994. However, the decline in mortality levelled off after 1987. In
      contrast to mortality, age-adjusted discharge rates increased by 47% for men and
      by 28% for women during the study period. The decline in mortality was equally
      distributed over the age groups, while the increase in the number of hospital
      admissions was more pronounced in the older age groups. The analyses by
      diagnostic subgroups of stroke showed the importance of increasing diagnostic
      capabilities in the hospital setting. The use of diagnostic subgroups in national
      mortality data was of limited value, illustrated by the fact that 70% of all
      stroke deaths in 1994 belonged to the ill-defined type of stroke.

PMID- 9648118
TI  - Stroke incidence and case fatality in two populations: the Auckland Stroke Study
      and the Copenhagen City Heart Study.
AB  - Comparison of stroke incidence and case fatality in different parts of the world
      provides information that may lead to a better understanding of the disease. In
      this report we have investigated these two aspects in two large populations, one
      in Auckland, New Zealand, and the other in Copenhagen, Denmark (the Copenhagen
      City Heart Study, CCHS). Incidence rates of stroke are higher for men than women
      in both studies. The stroke incidence rate ratios between Auckland men and CCHS
      men are significantly different in most age groups, whereas in women the
      incidence rates differ only in one age group. The age- and sex-adjusted incidence
      rates are higher in the CCHS for both men and women as compared to the Auckland
      Stroke Study. The age-adjusted incidence rate ratio is higher for men than women
      in both studies: 1.29 in the Auckland Stroke Study and 1.54 in the CCHS. The 28
      day case fatality is also higher in the CCHS than in Auckland and is higher for
      women than men in both studies. The incidence rate of stroke and the 28-day case
      fatality is higher in the CCHS as compared to the Auckland Stroke Study in both
      men and women. A very high proportion of smokers in CCHS may explain some of the
      differences in incidence rates in the two populations.

PMID- 9648119
TI  - The epidemiology of hospital-referred head injury in northern Norway.
AB  - This retrospective population-based survey describes the epidemiology of head
      injury in a defined population in Northern Norway. It includes all 247 patients
      with head injury referred to the University Hospital of Tromso, Norway, during
      1993. Head injury was defined as physical damage to the brain or skull caused by
      external force. The annual incidence rate of hospital-referred head injury was
      229/100,000 population with a male preponderance of 1.7:1.0. The cause was a fall
      in 62%, road traffic accident in 21% and assault in 7% of the cases. The observed
      incidence rate is low despite the use of wide inclusion criteria, probably due to
      a decrease in road traffic accidents. A further decrease in the number of head
      injuries in our region may be achieved by preventing falls.

PMID- 9648121
TI  - Multiple sclerosis and infectious childhood diseases.
AB  - To examine a possible relationship between infectious diseases and multiple
      sclerosis (MS) an enquiry was carried out among 606 MS patients in Switzerland.
      The data concerning their infectious childhood diseases were compared with
      epidemiological data for the normal Swiss population obtained from the Swiss
      Federal Health Office and from the Institute of Medical Statistics. The mean age
      of the MS patients was 50.7 years and the mean age at onset of multiple sclerosis
      was 33.8 years, significantly earlier in women (33.2 years) than in men (35.4
      years, p < 0.05). In 18.8% multiple members of the family were affected. In
      comparison with persons of the control population, MS patients had measles
      infection at a later age (6.4 vs. 7.5 years). The curve of the age at which
      several infectious childhood diseases occurred was shifted to higher ages for MS
      patients (p < 0.005) compared to normal controls for mumps (80.2% for MS vs.
      64.1% for controls in the age group 5-14 years), rubella (64.3% for MS vs. 48.4%
      for controls in the age group 5-14 years) and varicella (81.9% for MS vs. 39.0%
      for controls in the age group 5-19 years). For pertussis, however, there were
      more cases among those who later developed MS in the age group 1-9 years, which
      was earlier than in controls (86.0 vs. 56.7%). These results are compatible with
      the hypothesis that the risk of developing multiple sclerosis may be associated
      with acquiring certain infectious childhood diseases at a later stage in
      comparison to normal controls.

PMID- 9648120
TI  - The prevalence of cognitive impairment among nursing home residents in Taipei,
      Taiwan.
AB  - A random sample of nursing home residents over 65 years of age were interviewed.
      Two hundred ninety-two participants received the Short Portable Mental Status
      Questionnaire. Two hundred eleven were unable to answer the questionnaire, but
      their caregivers provided information about their daily activities and
      performance ability. We found that 255 (50.9%) fit our criteria of cognitive
      impairment and 236 (47.7%) had both impaired cognition and impaired performance
      in activities of daily living. Similar to statistics in the US, the prevalence of
      cognitive impairment in Taipei nursing home residents was much higher than that
      observed in the community elderly and probably in Taiwan as well. Therefore,
      public health care policy for cognitively impaired elderly in Taiwan should not
      simply rely on data from community studies.

PMID- 9648122
TI  - Factors associated with the time of presentation of acute stroke patients in an
      Israeli community hospital.
AB  - Recently it has been shown that effective treatment for acute stroke must be
      initiated within 3-6 h from onset. In order to determine whether this is feasible
      and the reasons for delayed presentation, a prospective study was conducted in a
      community hospital in Israel. Of the 216 patients enrolled, 18% arrived at the
      hospital within 90 min of stroke onset and 54% presented within 6 h. Important
      factors associated with early presentation included major stroke (as compared to
      mild stroke) and time of day of onset (afternoon as compared with nighttime).
      Further efforts must be made to shorten the delay in hospital arrival of acute
      stroke patients.

PMID- 9648123
TI  - Increased plasma vasopressin and atrial natriuretic peptide in chronic
      schizophrenic patients during abdominal surgery.
AB  - Chronic schizophrenic patients are reported to develop imbalanced water
      homeostasis by the pathological secretion of vasopressin and aldosterone. We
      measured plasma vasopressin, aldosterone and atrial natriuretic peptide in
      schizophrenic patients to elucidate the role of these hormones during a
      perioperative period. Eighteen schizophrenic patients with chronic antipsychotic
      drugs over 10 years and 22 as a control group who underwent elective lower
      abdominal surgery were the subjects of this study. In the schizophrenic patients,
      plasma aldosterone secretion was significantly inhibited, while plasma
      vasopressin and atrial natriuretic peptide were significantly increased during
      surgery. A good relationship (r = 0.69, p < 0.01) between plasma atrial
      natriuretic peptide and plasma osmolality was obtained 60 min after skin
      incision, but not before the induction of anesthesia. The findings suggest that
      chronic schizophrenic patients may develop an abnormal secretion of vasopressin,
      aldosterone and atrial natriuretic peptide during anesthesia.

PMID- 9648124
TI  - Season of birth in psychiatry. A review.
AB  - Numerous studies suggest that seasonal birth may play a pathogenic role in the
      development of mental disorders. A birth excess of 10% during winter and spring
      has been shown in schizophrenia. The few studies carried out on affective
      disorders revealed a significant increase of births in the first quarter of the
      year in bipolar disorders and major depressive disorder. Subjects with seasonal
      affective disorder show a peak of births in May. Data on personality, eating and
      'neurotic' disorders are less consistent. At the moment there are no data in the
      literature about anxiety disorders.

PMID- 9648125
TI  - Decreased blood levels of tumor necrosis factor-alpha in patients with obsessive
      compulsive disorder.
AB  - To investigate immune system function in obsessive-compulsive disorder (OCD) we
      measured plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1
      beta (IL-1 beta) and interleukin-6 (IL-6) in 14 drug-free obsessive-compulsive
      patients and 14 matched healthy controls. No significant differences were
      observed between patients and controls in plasma levels of IL-1 beta and IL-6,
      whereas plasma levels of TNF-alpha were significantly lower (p = 0.001) in the
      former. Blood levels of prolactin did not differ between the two groups, whereas
      plasma cortisol concentrations were significantly higher in patients than in
      healthy subjects (p = 0.02). No significant correlation was found between immune
      parameters, on the one hand, and endocrine or psychopathological measures on the
      other. These results suggest that OCD is associated with a decreased production
      in TNF-alpha, but normal synthesis of IL-1 beta and IL-6.

PMID- 9648126
TI  - Immunological dysfunction in schizophrenia: a systematic approach.
AB  - BACKGROUND: In the present study, immunological alterations were investigated as
      one possible factor contributing towards the pathogenesis of schizophrenia.
      Specifically cellular changes, deviating cytokine production and interfering
      variables were studied in order to improve our understanding of how these factors
      interact. METHOD: 44 acutely ill schizophrenics were compared with matched
      healthy controls. Cell numbers were determined by flow cytometry and cytokine
      production by whole blood assay and ELISA. A criss-cross technique was employed
      for the assessment of interfering serum factors. RESULTS: Cell counts for
      leukocytes, lymphocytes, pan T cells, activated T cells and the absolute B cell
      count of the schizophrenic patients were all within normal limits. The absolute
      and relative monocyte counts, the number of IL-2 receptor carrying T cells and
      the relative B cell count were slightly elevated. IL-2 and IFN-gamma production
      were increased while IL-10 production, the sIL-2R and cortisol levels remained
      unchanged. No interfering serum factors were detected. CONCLUSION: The deficient
      production of TH-1 cytokines in schizophrenia is not due either to a changed
      number of immunocompetent cells or to a counterregulation of the TH-2 cytokine IL
      10. Serum factors in in vitro testing are not responsible for the deficient
      cytokine production.

PMID- 9648127
TI  - Pathological regional cerebral blood flow in opiate-dependent patients during
      withdrawal: a HMPAO-SPECT study.
AB  - The aims of the present study were to investigate regional cerebral blood flow
      (rCBF) in heroin-dependent patients during withdrawal and to assess the relation
      between these changes and duration of heroin consumption and withdrawal data. The
      rCBF was measured using brain SPECT with 99mTc-HMPAO in 16 heroin-dependent
      patients during heroin withdrawal. Thirteen patients received levomethadone at
      the time of the SPECT scans. The images were analyzed both visually and
      quantitatively. A total of 21 hypoperfused brain regions were observed in 11 of
      the 16 patients. The temporal lobes were the most affected area, hypoperfusions
      of the right and left temporal lobe were observed in 5 and 5 patients,
      respectively. Three of the patients had a hypoperfusion of the right frontal
      lobe, 2 patients showed perfusion defects in the left frontal lobe, right
      parietal lobe and left parietal lobe. The results of the quantitative assessments
      of the rCBF were consistent with the results of the qualitative findings. The
      stepwise regression analysis showed a significant positive correlation (r = 0.54)
      between the dose of levomethadone at the time of the SPECT scan and the rCBF of
      the right parietal lobe. Other significant correlations between clinical data and
      rCBF were not found. The present results suggest brain perfusion abnormalities
      during heroin withdrawal in heroin-dependent patients, which are not due to the
      conditions of withdrawal.

PMID- 9648128
TI  - The influence of polypharmacological antidepressive treatment on central nervous
      information processing of depressed patients: implications for fitness to drive.
AB  - Antidepressive medication may cause impairment of psychomotor functioning
      relevant to psychosocial adaptation and fitness to drive. This impairment seems
      to be less severe by activating antidepressants (SSRI, MAOI). In clinical
      settings, however, polypharmacological treatment of depressive disorders is
      frequent. This study evaluates the influence of antidepressants and common
      comedications on central nervous information processing concerning the ability to
      drive. Inpatients (n = 44) with major depression (ICD-10) were investigated under
      steady state plasma level condition. The data were recorded by the Act & React
      Testsystem ART-90 and analyzed according to medication, severity of illness and
      age. 88.6% of the patients failed to pass all the tests. With respect to
      different groups of antidepressants, no differences in psychomotor reaction
      performance were observed in polydrug treatment. The impact of these results on
      the patients' fitness to drive is discussed.

PMID- 9648129
TI  - Grammatical choice and affective experience in a second-language test.
AB  - This study measured the affective experience of 12 subjects reading grammatically
      correct and incorrect versions of 50 sentences, Questionnaire I, in their second
      language (French). This was followed by a multiple choice grammar test,
      Questionnaire II, using the same 50 sentences and offering the correct and
      incorrect answers. Subjects tended to choose correct as well as incorrect
      responses corresponding to their highest affective rating within each entry. In
      all cases the subjects' behavior was higher than chance level and thus followed a
      trend to maximize pleasure. This result supports the hypothesis according to
      which the key to decision-making lies in the affective dimension of conscious
      experience.

PMID- 9648130
TI  - Pathophysiologically correlated deficits of information processing in obstructive
      sleep apnea patients.
AB  - In obstructive sleep apnea patients, who intermittently stop breathing at night
      for some seconds, functions of vigilance and attention seem to be impaired. The
      aim of our study was to investigate if nocturnal hypoxia as one possible
      detrimental factor is associated with the degree of modality shift effect
      expressing attention function at a very basic level of information processing.
      For the first time an experimental approach was applied to examine attention
      deficits in sleep apnea patients. Correlation analyses between pathophysiological
      parameters and attention function revealed a stronger association for the
      modality shift effect than for simple reaction times.

PMID- 9648131
TI  - Prefrontal hypooxygenation during language processing assessed with near-infrared
      spectroscopy.
AB  - Near-infrared spectroscopy (NIRS) is a noninvasive optical method which allows in
      vivo measurements of relative concentrations of oxygenated (O2Hb) and
      desoxygenated hemoglobin (HHb). It has been successfully applied to assess the
      blood oxygenation changes during cerebral ischemia in man. An interesting
      application of NIRS is the investigation of regional cerebral blood oxygenation
      during physiological brain functions. In the present study, left and right
      anterior prefrontal brain areas of 10 healthy subjects were investigated with 2
      channel NIRS during language processing (reading aloud). Nonverbal visual
      perception (picture observation) was performed as a control condition. Compared
      to the respective baseline conditions, a significant HHb increase and an O2Hb
      decrease as a trend were found during language processing but not during the
      nonverbal perceptual task, and no hemispheric differences were found. The
      metabolic activation patterns differed significantly between the tasks indicating
      the changes due to the language-related efforts but not to visual perception.
      Based on previous findings of metabolic brain imaging studies the results are
      best explained as a complementary phenomenon consisting in relative anterior
      prefrontal hypoperfusion due to a blood volume redistribution which favors
      language-related temporal areas.

PMID- 9648132
TI  - Nursing: a privilege.

PMID- 9648133
TI  - Is another RN shortage looming?

PMID- 9648134
TI  - The changing health care market: implications for nursing education in the coming
      decade.

PMID- 9648135
TI  - Corporate language and nursing practice.

PMID- 9648136
TI  - A middle-range theory of acute pain management: use in research.

PMID- 9648137
TI  - Practice-based research networks for nursing.

PMID- 9648138
TI  - Caring to confront in the workplace: an ethical perspective for nurses.

PMID- 9648139
TI  - Incremental approaches to necessary health care reform lead to more chaos.

PMID- 9648140
TI  - Overdrugging and undertreatment in primary health care.

PMID- 9648141
TI  - ["And what we are, you will be"--on the dignity and integrity of plasticized
      cadavers].

PMID- 9648142
TI  - [Myofibroblastic tumors. Brief review of clinical aspects, diagnosis and
      differential diagnosis].
AB  - This review summarizes myofibroblastic tumours that have been characterized in
      the last years. These lesions include: fibromatoses in adults and infants
      (infantile digital fibromatosis and infantile myofibromatosis); myofibroma of
      adults, an almost exclusively solitary lesion in the skin which is characterized
      morphologically as a biphasic lesion composed of spindle-shaped eosinophilic
      tumour cells and more primitive mesenchymal tumour cells associated with a
      haemangiopericytoma-like vasculature; dermatomyofibroma (plaque-like dermal
      fibromatosis), a band-like myofibroblastic proliferation in young female
      patients, which is mainly located in the periaxillar region and in which
      distinction from more aggressive, plaque-like variant of dermatofibrosarcoma
      protuberans is mandatory; myofibroblastoma of the breast, a well-circumscribed
      lesion composed of spindle shaped, desmin-positive tumour cells, which is seen
      mainly in elderly male patients and has to be distinguished from other spindle
      cell lesions of the breast; angiomyofibroblastoma, a well-circumscribed
      myofibroblastic neoplasm of the vulva and vagina composed of avoid to round myoid
      tumour cells with scattered multinucleated cells, which forms a continuous
      morphological spectrum with the clinically more aggressive angiomyxoma in this
      location; intranodal myofibroblastoma, a distinctive proliferation of
      myofibroblastic cells associated with so-called amianthoid fibres, which is seen
      most commonly in inguinal lymph nodes; myofibroblastoma/myofibroblastic tumour of
      soft tissues, a variably well-circumscribed myofibroblastic lesion which lacks
      atypia and is composed of actin and/or desmin positive tumour cells, and poorly
      delineated sarcomas with myofibroblastic differentiation (myofibrosarcoma).

PMID- 9648143
TI  - [Myofibroblasts. Review out outlook].
AB  - When studying inflammation and wound healing, peculiar fibroblasts with
      ultrastructural similarities to smooth muscle cells were described by a group of
      pathologists associated with Guido Majno (GM) and Giulio Gabbiani (GG),
      subsequently called myofibroblasts. Similar cells were also found later in human
      granulation tissue, palmar fibromatosis and in stromal reactions with invasive
      cancers. Their identification was facilitated by immunohistochemical methods.
      Some neoplastic cells, for instance in MFH, also revealed characteristics
      compatible with myofibroblasts. Myofibroblasts are conceived of as modulated
      fibroblasts. Cytokines may serve as mediators for activation and contractile
      modification of fibroblasts. In this context monitoring of a tumor-like
      overproduction of myofibroblasts or an underproduction with non-union of wounds
      might also be feasible. Moreover, better understanding of the role of
      myofibroblasts concerning the transition from in situ carcinomas into invasive
      growth may have therapeutic perspectives. Myofibroblasts apparently not only show
      a temporary existence in disease, but also can be found under normal conditions
      in several regions, such as the skin, periodontal ligaments, or pulmonary septa.

PMID- 9648144
TI  - [Liver changes in AIDS. Retrospective analysis of 227 autopsies of HIV-positive
      patients].
AB  - In a retrospective study of a 12-year period (1981-1992) liver histology was
      analyzed in 227 autopsied patients infected with the human immunodeficiency
      virus. Normal histology could only be documented in 29 patients (13%). In the
      majority of cases (56%) uncharacteristic changes were seen such as steatosis
      (34%), hemosiderosis (10%) or non-specific reactive hepatitis (7%). The finding
      of hepatic peliosis obtained in 4 patients was not associated with inflammatory
      liver changes, especially infections from Rochalimaea. Within a wide range of
      opportunistic infections recorded in 50 patients (22%), hepatitis caused by
      Cytomegalovirus (8%), Toxoplasma gondii (5%), Leishmania donovani (1%),
      Cryptococcus neoformans and Pneumocystis carinii (each 0.5%) was diagnosed. Among
      16 cases (7%) of mycobacterial liver infections typical mycobacteria were found
      in two patients and atypical mycobacteria in 14 patients, respectively. In 23
      patients (10%) chronic viral hepatitis, caused by HBV (7%) or HCV infections
      (3%), respectively, was observed. Hepatitis was typed as mild only in each 5
      patients with HBV or HCV infection, whereas the remaining cases showed a
      transition towards cirrhosis. Two patients with HBV-associated cirrhosis
      developed hepatocellular carcinoma. The remaining 32 malignant liver tumors
      represented secondary neoplasms, including 13 cases of non-Hodgkin's lymphomas.

PMID- 9648145
TI  - [Differential diagnosis of squamous epithelial carcinoma of the salivary glands].
AB  - Primary squamous cell carcinomas (SCC) of the salivary glands are localized
      predominantly in the major salivary glands and must be distinguished from
      metastases of extraglandular SCC of the skin, especially the head and neck area.
      Squamous cell metaplasia in non-tumourous diseases of the salivary gland (e.g.
      necrotizing sialometaplasia) as well as in benign or malignant salivary gland
      tumours (e.g. metaplastic Warthin tumour) can simulate SCC. Other differential
      diagnostic problems are the structural variants of SCC which develop
      predominantly in the minor salivary glands, but not in the major salivary glands.
      Special types include the very rare adenoid SCC with pseudoglandular structures
      as the result of acantholysis, the biphasic adenosquamous carcinoma with
      differentiation as SCC and adenocarcinoma, the biphasic basaloid squamous
      carcinoma with a structure as SCC and solid basaloid carcinoma (analogous to the
      solid type of adenoid-cystic carcinoma) and the poorly differentiated
      mucoepidermoid carcinoma (grade III) with biphasic structure of undifferentiated
      epidermoid and intermediate cells as well as inclusion of small groups of mucous
      producing goblet cells. The differential diagnostic criteria are analysed
      concerning prognosis and treatment.

PMID- 9648146
TI  - [Diagnostic value of stomach biopsy in comparison with surgical specimen in
      gastric B-cell lymphomas of the MALT type].
AB  - Diagnostic und therapeutic management of gastric lymphomas of the mucosa
      associated lymphoid tissue type (MALT-type lymphomas) is often based exclusively
      on the evaluation of biopsy material. To evaluate the diagnostic value of gastric
      biopsies in gastric MALT-type lymphomas, biopsies--on average six per patient-
      and subsequent surgical specimens of 64 patients were compared at the Institute
      of Pathology, University of Wurzburg. Tumor diagnosis and tumor gradind were
      assessed. Using biopsy specimens, primary gastric MALT-type lymphomas were
      correctly diagnosed by local pathologists in 69% of cases, but correctly graded
      as low-grade, high-grade or secondary high-grade lymphomas in only 41%. When
      immunohistochemistry and molecular biological techniques were applied in addition
      to conventional histology, diagnosis of gastric MALT-type lymphoma was achieved
      in biopsies in 95% of cases at the Institute of Pathology Wurzburg, but correct
      grading in only 73%. In secondary high-grade MALT-type lymphomas, both components
      -the high-grade and the low-grade component--were identified in gastric biopsies
      in only 33% of cases. Diagnostic accuracy in gastric lymphomas based on biopsies
      is limited by biopsy artefacts, but improved by using immunohistochemistry and
      molecular biological techniques. Particularly in secondary high-grade MALT-type
      lymphomas the correct diagnosis is often missed when using biopsies, due to a low
      number of biopsy specimens.

PMID- 9648147
TI  - [Pleural reaction pattern after talc pleurodesis].
AB  - Because of the rising importance of talcum pleurodesis in the therapeutic
      management of malignant and benign pleural effusions in Germany, pleural samples
      after talcum pleurodesis were compared to microscopic, immunohistochemical, and
      scanning electron microscopy findings after Tetracyclin and Novantron pleurodesis
      in 24 patients up to 18 months after intrapleural therapy. The histomorphological
      findings after talcum pleurodesis show an early phase of up to 4 weeks,
      characterized by the presence of talcum-containing granulation tissue with giant
      cell foreign-body reaction, and a subsequent late phase with organization of the
      granulation tissue and connective tissue formation and obliteration of the pleura
      sheets. The resulting characteristic linear talcum zone in the pleural connective
      tissue is missing in cases with tumorous infiltration of the pleura. Continuous
      fibroblast activation, e.g., by macrophage or foreign-body giant-cell-released
      mediators, seems to be the decisive factor in the fibrosing process. No therapy
      related tumor growth alterations could be demonstrated.

PMID- 9648148
TI  - [Adult giant cell hepatitis with fatal outcome. Clinicopathologic case report and
      reflections on pathogenesis].
AB  - The occurrence of plasmodial giant cells in the liver is probably a morphological
      reaction pattern with the most diverse causes. In babies and infants, these
      changes occur in particular in neonatal hepatitis and intrahepatic and
      extrahepatic bile duct atresia. Viral infections and/or autoimmune reactions are
      discussed etiologically in giant cell hepatitis in adults (adult gaint cell
      hepatitis, AGCH), which is much rarer. In some of the cases, there were
      conspicuously high titers against paramyxoviruses. Giant cell hepatitis can occur
      in the course of HIV infection. These both indicate an infectious cause. However,
      the disease cannot be transmitted to chimpanzees. Apart from our case, only one
      further case is described in the literature in which a completed hepatitis A
      infection could be demonstrated serologically. In addition, the titer of
      antinuclear antibodies was raised in our patient. This autoimmune phenomenon is
      probably of crucial pathogenetic significance in our patient, especially since a
      hepatitis A infection on its own does not afford an adequate etiological
      explanation for the form of chronic and active hepatitis with consecutive
      cirrhotic transformation observed here.

PMID- 9648149
TI  - [Mesoblastic nephroma in adulthood].
AB  - We report a 44-year-old female patient who underwent surgery because of a
      suspected primary tumor of the renal pelvis in imaging procedures. Histology
      revealed the diagnosis of mesoblastic nephroma. This tumor represents a special
      entity of nephroblastoma that rarely occurs in adults. There is no unanimous
      opinion on the biological behavior of mesoblastic nephroma because the tumor
      behaves differently. The question of whether nephrectomy is indicated if there
      are no malignant features is also open. The decision depends on the given case.
      Nephrectomy can only be avoided if the intraoperative situation allows the tumor
      to be removed with an adequate distance from healthy tissue. The safety margin is
      necessary because mesoblastic nephroma shows fingerlike spread into the
      surrounding tissue.

PMID- 9648150
TI  - [Glomerulopathy in Denys-Drash syndrome. Case report of a model disease].
AB  - About 10% of all nephroblastomas (Wilms' tumor) present as part of malformation
      syndromes. The Denys-Drash syndrome (DDS) comprises pseudohermaphroditism,
      glomerulopathy and, early, often bilateral Wilms' tumors. A nephrectomy was
      performed in a 4-month-old girl because of a Wilms' tumor. Two months later, low
      serum albumin levels and proteinuria had developed. A biopsy from the remaining
      kidney showed a glomerulopathy which could also be seen in the nephrectomy
      specimen. The morphology was highly characteristic: the innermost layer of the
      kidney cortex exhibited augmentation of the mesangial matrix only; the
      intermediate layer showed severe sclerosis of glomeruli with deposition of
      fibrillary material; and the subcapsular layer revealed very small glomeruli and
      atrophic tubuli. Fifteen months later, peritoneal dialysis was necessary and due
      to the high risk of tumor development in the remaining kidney, a nephrectomy was
      performed. Molecular analysis revealed a point mutation within exon 9 of the WT1
      gene (394 ARG-->TRP), which was homozygous in the tumor and heterozygous within
      renal parenchyma. The DDS is caused by a mutation in the WT1 gene on chromosome
      11p13 which occurs during oogenesis or spermiogenesis. The WT1 gene is highly
      expressed during the development of the genitalia and the kidney; damage in one
      allele only causes the malformation syndrome. Loss of the second allele of the
      WT1 gene constitutes the second step of tumorigenesis. The appearance of Wilms'
      tumors derived from cells homozygous for the mutation reveals the function of the
      WT1 gene as a tumor suppressor gene.

PMID- 9648151
TI  - [Standardization of cytopathologic diagnosis].

PMID- 9648152
TI  - So-called neoplastic myoepithelial cells in chondroid syringomas/mixed tumors of
      the skin: their subtypes and immunohistochemical analysis.
AB  - An immunohistochemical study of nine cases of chondroid syringomas/mixed tumors
      of the skin was performed to elucidate the nature of the so-called neoplastic
      myoepithelial cells (NMEC) in tumor tissues. These nine tumors contained NMEC of
      considerable variability in number from one tumor to another. These NMEC were
      classified into three types: (i) hyaline cells (plasmacytoid cells); (ii) spindle
      NMEC; and (iii) polyhedral cells. They showed different immunostaining patterns,
      as the following describes. Cytokeratin 14 was positive in most of the spindle
      NMEC and a large number of the polyhedral cells, and in a small number of the
      hyaline cells. Concerning low molecular weight cytokeratins, most of the hyaline
      cells showed immunoreactivity, whereas they were negative in many of the spindle
      NMEC and were expressed only in a small number of the polyhedral cells. alpha
      Smooth muscle actin and muscle-specific actin were positive in the spindle NMEC
      but negative in any of the hyaline cells and polyhedral cells. These findings
      strongly indicate that the hyaline cells and the spindle NMEC are of the simple
      epithelial and myoepithelial types, respectively. The findings also suggest that
      the polyhedral cells show differentiation toward basal cells of the sweat gland
      dermal ducts or myoepithelial cells.

PMID- 9648153
TI  - Vascular invasion of O-1N, hamster squamous cell carcinoma with high potential of
      lymph node metastasis: ultrastructural comparison between lymphatics and blood
      vessels.
AB  - The ultrastructural modes of lymphatic and blood vessel invasions were studied
      comparatively in hamsters with squamous cell carcinoma (O-1N) that had a high
      potential for lymph node metastasis. The endothelial injury, which was caused by
      mechanical stretching with the growth of O-1N, was the initial and characteristic
      feature common to both vascular invasions. Tumor cell nests penetrating the
      lymphatic lumen through disrupted endothelial cells still maintained their volume
      and continuity to the underlying tumor cell nests. In contrast, pronounced
      microthrombotic and neutrophilic reactions occurred at the site of blood vessel
      penetration. Within the lymphatic lumen, large clusters of O-1N cells were kept
      longer in spite of lymphocytic and macrophagic reactions. In blood vessels,
      clusters of tumor cells that had passed through dense fibrin layers were reduced
      in size and further disintegrated into smaller pieces by neutrophils. In
      conclusion, lymphatic invasion is a mechanical process, and smooth and direct
      invasion of large tumor cell nests into lymphatic vessels is responsible for
      causing more prompt and frequent lymph node metastasis in O-1N than a
      hematogenous type.

PMID- 9648154
TI  - DNA analysis at p53 locus in carcinomas arising from pleomorphic adenomas of
      salivary glands: comparison of molecular study and p53 immunostaining.
AB  - Where and how frequently p53 abnormalities are involved in the development of
      pleomorphic adenoma (PA) and its malignant progression to carcinoma was
      investigated. The presence of p53 gene abnormalities was analyzed in eight
      patients with carcinoma in pleomorphic adenoma (CPA) by polymerase chain reaction
      (PCR)-based assays and immunohistochemistry. Normal salivary gland tissue,
      adenomatous, transitional and carcinomatous areas were microdissected from
      archival microslides and analyzed for allelic deletions of the p53 gene using two
      microsatellite markers at the p53 locus; dinucleotide (CA)n repeat and
      pentanucleotide (AAAAT)n repeat. Loss of heterozygosity (LOH) of the p53 gene was
      detected in 57% of adenomas, 86% of transitional lesions and 86% of carcinomas.
      In contrast, overexpression of p53 oncoprotein was noted immunohistochemically in
      13% of adenomas, 50% of transitional areas and 75% of carcinomas. All of the
      tumors with immunoreactivity for p53 oncoprotein demonstrated LOH. Moreover, when
      LOH was present in adenomatous or transitional areas, the identical LOH was
      always detected in the corresponding carcinomatous areas in the same CPA tumors.
      These findings indicate that p53 gene mutation is an early event and occurs
      frequently at an early stage of precancerous lesions and may be responsible for
      most cases of malignant transformation of PA.

PMID- 9648155
TI  - DNA analysis at p53 locus in adenoid cystic carcinoma: comparison of molecular
      study and p53 immunostaining.
AB  - Abnormalities of the p53 tumor suppressor gene were investigated in 22 foci from
      14 adenoid cystic carcinomas (ACC) by polymerase chain reaction (PCR)-based
      assays for dinucleotide (CA)n and pentanucleotide (AAAAT)n repeat polymorphisms
      and by immunohistochemical staining for oncoprotein expression. Adenoid cystic
      carcinomas were divided into lower grade (tubular and cribriform) subtypes and
      higher grade (trabecular and solid) subtypes. Histologically identified tumor
      cells were precisely microdissected from archival microslides and were used for
      molecular analysis. The overall frequency of p53 gene mutations detected by PCR
      loss-of-heterozygosity (LOH) analysis was 57% and was higher than the frequency
      of over-expression of p53 oncoprotein detected by immunostaining (43%). In the
      molecular analysis of individual histological subtype foci, the number of foci
      with p53 gene mutation was significantly greater in the higher grade subtype foci
      than in the lower grade subtype foci and was greatest in solid-type foci (100%).
      In all six tumors in which histologically different foci were present in the same
      tumors, mutations of the p53 gene were detected. When tumor heterogeneity of the
      p53 gene was present among different histological foci in the same tumors, the
      mutations were always detected in the higher grade foci. When lower and higher
      grade foci were present in the same tumors, the identical mutations detected in
      the lower grade foci were present in the corresponding higher grade foci. These
      findings indicate that abnormalities of the p53 gene are involved in
      carcinogenesis and/or progression of this tumor and, furthermore, suggest that
      molecular analyses of ACC may provide information of prognostic importance.

PMID- 9648156
TI  - Overexpression of p53 protein correlates with a high risk of malignant
      transformation of adenomas in patients with multiple colorectal adenomas.
AB  - To assess the correlation of p53 oncoprotein expression with the high risk of
      developing carcinomas in patients with multiple colorectal adenomas, 25 cases
      with histologic carcinoma in adenoma (CIA) were examined by immunohistochemistry
      using a monoclonal antibody specific to human p53 protein (wild and mutant). The
      25 cases were classified into multiple and single groups. The former contained 13
      cases with synchronous multiple colorectal adenomas (one to six adenomas) and
      adenocarcinoma. The latter included 12 cases with single CIA only. This study
      revealed an overall incidence of 57.14% of p53 overexpression in carcinomatous
      lesions and 31.9% in adenomatous lesions, which was statistically significant (P
      < 0.05). The carcinomatous lesions showed a diffuse staining pattern, whereas the
      adenomatous lesions showed a focal pattern. A significant finding was that the
      incidence of p53 overexpression was significantly higher in multiple groups
      (81.25%) than in single groups (31.43%) in the carcinomatous (P < 0.01) rather
      than in the adenomatous (P < 0.05) lesions. There were no correlations between
      p53 overexpression and proliferation activity or carcinoembryonic antigen
      expression. The results indicate that p53 abnormality may be an important genetic
      factor responsible for the high risk of developing carcinomas in patients with
      multiple adenomas.

PMID- 9648157
TI  - Sebaceous carcinoma of the submandibular gland with high-grade malignancy: report
      of a case.
AB  - A case of sebaceous carcinoma arising in the left submandibular gland of a 66
      year-old man is reported. The clinical and pathological examinations revealed a
      carcinoma, which was to salivary gland in origin, with regional lymph nodal
      metastases. Pathological findings showed features of high-grade sebaceous
      carcinoma with spindle myoepitheliomatous differentiation. Neither squamous cell
      nor duct epithelial-like cell differentiation was noted. Immunohistochemically,
      tumor cells were positive for cytokeratin, S-100 protein and vimentin. Lipid was
      demonstrated in the cytoplasm of the tumor cells. Ultrastructurally, tumor cells
      contained numerous intracytoplasmic lipid droplets. Myoepitheliomatous
      differentiation is rare in sebaceous carcinoma of the salivary gland. Presented
      is the second reported case of sebaceous carcinoma arising in the submandibular
      gland.

PMID- 9648158
TI  - Angiomyofibroblastoma of the vulva: a mitotically active variant?
AB  - A case of angiomyofibroblastoma in a 48-year-old woman is reported. The tumor
      occurred as a left vulval mass and was treated by simple excision. It was located
      in the subcutaneous tissue of the left vulva and was well circumscribed,
      measuring 2.8 x 2.7 x 2.5 cm. Microscopically, the tumor was composed of
      hypocellular and cellular areas with well-developed small vessels. Spindle or
      polygonal cells were arranged with perivascular accentuation in an edematous or
      fibrocollagenous background. Some spindle-shaped or polygonal stromal cells were
      also arranged in epithelioid nests. In some areas, mitoses were frequent (maximum
      3/10 high-power field). Immunohistochemically, the stromal cells were positive
      for vimentin and desmin, but negative for alpha-smooth muscle actin, S-100,
      neurofilament, estrogen receptor, progesterone receptor, CD31 and CD34. The
      average labeling index of Ki-67 in stromal cells was 3.1%. Ultrastructural
      analysis demonstrated that the stromal cells adhered with primitive junctions and
      contained intermediate filaments with no focal density in the cytoplasm. These
      findings were consistent with angiomyofibroblastoma, although previously reported
      cases did not show so many mitoses. Therefore, this case was suggested to be a
      mitotically active variant.

PMID- 9648159
TI  - Extrauterine low-grade endometrial stromal sarcoma: report of three cases.
AB  - Three cases of rare low-grade endometrial stromal sarcoma of the extrauterine
      tissue are presented. Each one occurred in the ovary, pelvic and abdominal
      cavities. Two were associated with endometriosis. Histologically, the tumors were
      characterized by an infiltrative and diffuse proliferation of uniform round or
      oval cells, abundant small vessels, low mitotic activity, the presence of foam
      cells and vascular invasion. Immunohistochemically, all tumors expressed
      vimentin, muscle markers (desmin, muscle-specific actin and alpha-smooth muscle
      actin) and progesterone receptors. Two tumors were diploid and one was aneuploid
      by flow cytometry. All patients were well with no evidence of disease 16-39
      months after surgery. It is suggested that this neoplasm may arise with or
      without endometriosis under hormonal influence. This rare variant of Mullerian
      tumors should not be confused with adenosarcoma and soft tissue tumors, such as
      smooth muscle tumors and solitary fibrous tumor.

PMID- 9648160
TI  - Small cell carcinoma of the gall-bladder with intestinal metaplastic epithelium.
AB  - A case of small cell carcinoma of the gall-bladder is described.
      Immunohistochemically, the tumor cells were positive for chromogranin A,
      synaptophysin and neuronspecific enolase, which suggests that they derived from
      neuroendocrine cells. The overlying and surrounding epithelium of the tumor
      showed intestinal metaplasia including goblet cells, pseudopyloric glands,
      Paneth's cells, and chromogranin A and synaptophysin-positive endocrine cells.
      Definite adenocarcinoma was absent. The endocrine cells in the epithelium were
      more numerous in the vicinity of the tumor. The present case supports the
      supposition that endocrine cell tumor (including small cell carcinoma) of the
      gall-bladder may develop from endocrine cells of the intestinal metaplastic
      lesion.

PMID- 9648161
TI  - Intranodal palisaded myofibroblastoma with so-called amianthoid fibers: a report
      of two cases with a review of the literature.
AB  - Two cases of intranodal myofibroblastoma, a rare primary spindle cell tumor of
      the lymph node, are described. The tumors arose in the inguinal or proximal
      region of the thigh of one middle-aged and one elderly Japanese male. The tumors
      were well-demarcated and composed of a fascicular proliferation of spindle cells
      with focal nuclear palisading and acellular stellate-shaped collagen-rich areas
      (so-called amianthoid fibers), and were associated with hemorrhagic areas.
      Immunohistochemically, the tumor cells were positive for vimentin and muscle
      actin. Together with ultrastructural findings of intracytoplasmic microfilaments
      with focal densities and profiles of well-developed, rough endoplasmic reticulum,
      these features reinforced the conclusion of myofibroblastic or smooth muscle
      differentiation of the tumor cells. One of the tumors was analyzed by flow
      cytometry and was shown to be DNA diploid. The present report provides
      clinicopathological findings of the first two Japanese cases of intranodal
      myofibroblastoma.

PMID- 9648162
TI  - Multiple organ failure associated with extensive metastatic calcification in a
      patient with an intermediate state of human T lymphotropic virus type I (HTLV-I)
      infection: report of an autopsy case.
AB  - A patient with an intermediate state of human T lymphotropic virus type I (HTLV
      I) infection and in whom autopsy showed multiple organ failure (MOF) associated
      with extensive metastatic calcification in systemic organs is described. A 56
      year-old man presented with signs and symptoms of advanced cardiac insufficiency,
      respiratory disturbance and renal failure. Serologically, the anti-human T
      lymphotropic virus type I (HTLV-I) antibody titer and the levels of both calcium
      and parathyroid hormone-related peptide (PTHrP) were distinctly elevated. These
      data suggested a diagnosis of adult T cell lymphoma/leukemia (ATLL). However,
      examination of a peripheral blood sample revealed only a few atypical lymphoid
      cells (3%) associated with mild leukocytosis (white blood cell count, 13.7 x
      10(3)/mm3). Lymph node swelling was systemic but mild, with some nodes up to 10
      mm in diameter. The patient died of MOF. Adult T cell leukemia/lymphoma was
      unable to be diagnosed definitively because of the short duration of laboratory
      abnormalities and because of the discrepancy between the laboratory data and the
      magnitude of lymphoproliferation in both the lymph nodes and peripheral blood. At
      autopsy, the most conspicuous finding was extensive metastatic calcification in
      the multiple organs, including the heart, lungs, kidneys, tongue, liver,
      pancreas, spleen and systemic arterial walls. Very small numbers of medium-sized
      atypical lymphoid cells admixed with small reactive lymphocytes were identified
      in multiple organs, with no evidence of massive infiltration. Molecular analyses
      could not detect monoclonal integration of HTLV-I provirus DNA or monoclonality
      of T cell lineage cells. Parathyroid hormone-related peptide was demonstrated in
      the cytoplasm of the atypical lymphoid cells on immunohistochemical examination.
      The bone trabeculae generally showed distinct evidence of resorption associated
      with marked proliferation of osteoclasts. These findings suggested that the
      hypercalcemia in the present case was categorized as humoral hypercalcemia of
      malignancy rather than local osteolytic hypercalcemia.

PMID- 9648163
TI  - MUC-1 mucin expression in invasive areas of intraductal papillary mucinous tumors
      of the pancreas.
AB  - The expression of MUC-1 mucin (membrane-associated mucin) and MUC-2 mucin
      (secretory mucin) were immunohistochemically examined in 46 invasive ductal
      carcinomas (IDC) and 16 intraductal papillary mucinous tumors (IPMT) of the
      pancreas. Intraductal papillary mucinous tumors usually reveal expansive growth.
      However, of the 16 IPMT examined in the present study, three showed an invasive
      growth pattern, which was similar to 'mucinous carcinoma', around the non
      invasive growth areas. Of 46 IDC, MUC-1 mucin detected by monoclonal antibodies,
      DF3 and MY.1E12, was expressed in 44 cases (96%) and in 45 cases (98%),
      respectively, whereas MUC-2 mucin detected by polyclonal antibody, anti-MRP, was
      not expressed in any of the cases (0%). In contrast, in the non-invasive growth
      areas of the 16 IPMT, MUC-1 mucin detected by DF3 and MY.1E12 was expressed in
      four cases (25%) and in six cases (38%), respectively, whereas MUC-2 mucin
      detected by anti-MRP was expressed in 13 cases (81%). The invasive growth areas
      of the three IPMT showed positive expression of MUC-1 mucins detected by DF3 and
      MY.1E12, although the non-invasive growth areas showed negative expression of MUC
      1 mucins, except for their focal positive expression in one of the three cases.
      These findings indicate that the invasive growth areas of IPMT acquire a
      characteristic of MUC-1 mucin expression that is usually seen in IDC.

PMID- 9648164
TI  - More on pediatric dermatology.

PMID- 9648165
TI  - Immunization rates: where is the help when we need it?

PMID- 9648166
TI  - When you run the zoo: the need for residents to learn strategies for delivering
      childhood immunizations.

PMID- 9648167
TI  - Childhood vaccination successes, yes, but the job is not finished.

PMID- 9648168
TI  - 1998 immunization schedule changes and clarifications.

PMID- 9648169
TI  - Immunization registries: the cornerstone of childhood immunization in the 21st
      century.

PMID- 9648170
TI  - Evidence on office-based interventions to improve childhood immunization
      delivery.

PMID- 9648171
TI  - Barriers to immunization and missed opportunities.

PMID- 9648173
TI  - What is physiotherapy?

PMID- 9648172
TI  - Taking the sting out of shots: control of vaccination-associated pain and adverse
      reactions.

PMID- 9648174
TI  - Breathing patterns and heart rate during simulated occupational upper limb tasks
      in normal subjects.
AB  - BACKGROUND AND PURPOSE: Despite the arms being used extensively in the
      performance of many occupational tasks, little is known about the pattern of
      breathing and physiological cost of such work. The purpose of this study was to
      establish whether a simple change in arm support could alter the workload,
      pattern of breathing and respiratory muscle recruitment during a low intensity
      arm task. METHODS: Ten normal subjects performed a simulated work task when
      sitting, once with the arms supported and once unsupported. Subjects were
      required, over a five-minute period, to repeatedly pick up a 2 kg object, inspect
      and hold it for 15 seconds and then pack it in a box. Breathing pattern
      responses, measured by pneumotachograph and respiratory inductive
      plethysmography, were minute ventilation (VE), respiratory frequency (Rf), tidal
      volume (VT) and change in functional residual capacity (FRC). RESULTS: The main
      findings were that unsupported arm work was more physiologically demanding than
      supported arm work. During work VE increased as a result of a change in
      respiratory frequency but not VT which was much more limited when the arms were
      unsupported. At the completion of activity, when the arms were unloaded, VT
      initially increased as VE decreased. FRC and VT were reduced during arm work and
      increased during recovery, mainly as a result of a change in ribcage excursion.
      CONCLUSIONS: These findings support the theory that during arms activity,
      intercostal and accessory respiratory muscles act to stabilize the arms and
      torso, impeding chest wall movement and shifting the respiratory load from these
      muscles to the diaphragm. This may adversely effect performance of workers who
      have ventilatory limits to arm work tasks.

PMID- 9648175
TI  - Motivating factors for return to work.
AB  - BACKGROUND AND PURPOSE: A new concept to increase return to work for patients
      listed as sick with chronic musculoskeletal pain has been used at a
      rehabilitation centre in Lulea, Sweden. The programme includes work for three
      days a week and intensive rehabilitation for two days a week, for 12 weeks, as a
      combination of 'on the job' training and rehabilitation after a period off work
      sick. The rehabilitation programme focused on pain reduction, identifying and
      finding solutions to pain problems in actual work and life situations and
      training of the functional capacities needed in the work and life situation. The
      aim of the study was to describe patients' perceptions of motivating factors for
      return to work. METHODS: A phenomenological method was used. A naive reading of
      interview notes was followed by structural analyses and reflections on the
      interpreted whole. Inclusion criteria for the study were musculoskeletal pain for
      at least one year and a period of at least four weeks' sick leave during that
      time. Ten patients, aged 30-54 years, participated in the study. An initial
      conceptual framework was developed to inform the scope of the study and to guide
      data collection and analysis. RESULTS: Different factors in the study framework
      influenced motivation to return to work. Among structural factors the division of
      labour at work was the most important motivator, particularly the ability to do
      as much as work colleagues, quantitatively and qualitatively. All the patients
      had jobs in the healthcare or service sectors, jobs with many social contacts.
      They perceived their work task content as being of minor importance compared to
      whether the tasks were perceived as meaningful or highly needed by others. All
      wanted a meaningful job content and a job which they could do in a satisfactory
      way according to their own norms and compared to colleagues. This highly
      increased motivation for return to work. Relationships (in terms of co-operation
      with colleagues and service to patients or clients) were important motivating
      factors for return to work. Self-confidence was a new factor of importance for
      return to work; work tasks had to be meaningful and needed by others, work must
      be done in a way satisfactory for the individual and in a way that was acceptable
      to others in the group. Everyday responsibility, feedback and support in daily
      work tasks were important. These aspects increased self-confidence. The results
      supported the development of a new conceptual framework for possible motivating
      factors for return to work. CONCLUSIONS: Structure, content, relationships,
      health and self-confidence were all important motivating factors for return to
      work.

PMID- 9648176
TI  - Changes in balance and locomotion measures during rehabilitation following
      stroke.
AB  - BACKGROUND AND PURPOSE: This study aimed to examine the utility of a number of
      measures of balance and locomotion for the purpose of measuring change in a group
      of stroke patients undergoing in-patient rehabilitation. The aim was to select a
      core group of measures based on empirical evidence of usefulness rather than
      personal preference. METHODS: Twenty-nine stroke patients undergoing in-patient
      rehabilitation (mean age 71.8 +/- 10.5 years; 66% male) participated in the
      study. A prospective design was utilized with repeated measurement undertaken at
      four, six and eight weeks post-stroke. Static standing, the Clinical Test of
      Sensory Interaction of Balance (CTSIB) (Shumway-Cook & Horak, 1986), functional
      reach (FR), repetitive reach (RR), step test (ST), gait velocity, stride length
      and the Motor Assessment Scale (Carr et al., 1985) (walking item) were assessed
      at each interval. RESULTS: All measures of dynamic balance showed significant
      change over the four-week measurement period (p < 0.0036). Factor analysis
      identified two factors which grouped tests into static and dynamic, with a trend
      towards a third factor incorporating bipedal dynamic tests. Tests of static
      balance suffered from ceiling effects, whereas dynamic tests of balance and gait
      suffered from floor effects. Dynamic tests were more responsive (Standardized
      Response Measure (SRM) > 0.75) to change over the rehabilitation period than
      static tests. CONCLUSIONS: The findings suggest that a clinically useful and
      responsive balance and mobility test battery should include one component of the
      CTSIB (Shumway-Cook & Horak, 1986), RR (step stance), ST and gait velocity.

PMID- 9648177
TI  - Curricular content on urinary incontinence in entry-level physical therapy
      programmes in three countries.
AB  - BACKGROUND AND PURPOSE: Urinary incontinence (UI) is a significant psychological,
      social and healthcare problem across the lifespan. Although there is evidence of
      physical therapy (PT) efficacy, no literature was located pertaining to UI in PT
      curricula. The aim was to compare curricular content on UI (of non-neuropathic
      origin) in PT programmes in Canada, the UK and the USA. The study subjects were
      PT educators in entry-level programmes. METHODS: All Canadian PT programmes (13)
      were surveyed. Stratification was used to make random samples of PT programmes:
      50% of UK (13/26) and 50% of USA (69/136). A questionnaire was used to obtain
      information on: degree level, programme length, specific courses, time allotted,
      UI topics, teaching method(s), the professional teaching patients with UI and
      reasons for non-inclusion in the study. One follow-up letter was sent. Results
      are presented as frequencies and percentages. RESULTS: Overall, the response rate
      was 62.8%; country response rates were: Canada 92.3%; UK 76.9% and USA 53.6%. UI
      was taught in 80% of Canadian, 90% of UK (which gave the most time to teaching on
      UI: 70% > 60 minutes) and 78.4% of USA PT programmes. Kegel exercises were taught
      in all three countries (> 81.1%) and electrical stimulation in > 65%. Theory only
      was the primary method of teaching in all countries (> 64.9%). Physical
      therapists were reported to have a major role in treating patients with UI
      (Canada > 75%; UK 100%; USA 70.3%). CONCLUSIONS: With Kegel exercises and
      electrical stimulation taught in two-thirds of all programmes physical therapy
      graduates may have some knowledge of UI management. However, for the UK and USA
      programmes data are from only 38.5% and 27% respectively. As the common method of
      teaching on UI was by theory only, graduating physical therapists may lack the
      clinical skills to apply assessment and treatment techniques.

PMID- 9648178
TI  - Inter- and intra-tester reliability of the Balance Performance Monitor in a non
      patient population.
AB  - BACKGROUND AND PURPOSE: There is a growing interest in the measurement and
      evaluation of balance deficits and a number of instruments for measurement are
      now available. However, few data exist that accurately describe the reliability
      when using these measurement tools. This study was designed to evaluate the inter
      and intra-tester reliability of using the Balance Performance Monitor (BPM) (SMS
      Healthcare) in a non-patient population. METHODS: A total of 58 subjects (mean
      age 29.83 years (+/- 9.44 years)) and three testers participated in two separate
      experiments. Intra Class Correlation Coefficients (ICCs) and coefficients of
      variation were used to describe the reliability of two different protocols for
      positioning subjects on the footplates of the BPM. RESULTS: Measurements of
      weight distribution showed high and significant inter- and intra-tester
      reliability for both protocols (ICCs ranging from 0.720 to 0.868). Sway
      measurements showed more limited reliability (ICCs ranging from 0.183 to 0.775).
      Coefficients of variation were low for weight distribution measurements and high
      for sway measurements. CONCLUSIONS: Taking the mean of three measurements is
      recommended for both the weight distribution and the sway measurements as it has
      shown to produce acceptable measurement results.

PMID- 9648179
TI  - An unlikely case for successful rehabilitation?

PMID- 9648180
TI  - Associated reactions: their value in clinical practice?

PMID- 9648181
TI  - Normal mechanisms of heat and moisture exchange in the respiratory tract.
AB  - The initial conditioning of the inhaled gases occurs in the upper respiratory
      tract. The conditioned gases are at approximately 32 degrees C and more than 95%
      relative humidity as they enter the lower respiratory tract. This level of heat
      and humidity will preserve the body's defense mechanisms. When the upper airway
      is bypassed the gases being delivered to the lower airways need to be as close to
      physiologic levels as possible based on the length of time the endotracheal tube
      will be in place. The delivery of gases above or below normal physiologic levels
      has been shown to produce clinical problems.

PMID- 9648182
TI  - The effects of inadequate humidity.
AB  - The use of heated humidification in adults does not appear to be an important
      factor in maintaining body temperature in adults. Heat and moisture losses
      certainly can be reduced with heated humidification, but the contribution to
      temperature regulation appears small. The use of an HME reduces heat loss form
      the respiratory tract, but this loss is minute compared with losses from the
      skin, fluid administration, and the operative site. In neonates, the use of
      heated humidification during surgery may help contribute to thermal balance owing
      to the unique issues of temperature regulation and control in these patients.

PMID- 9648183
TI  - The effects of excessive humidity.
AB  - Humidification devices and techniques can expose the airway mucosa to a wide
      range of gas temperatures and humidities, some of which are excessive and may
      cause injury. Humidified gas is a carrier of both water and energy. The volume of
      water in the gas stream depends on whether the water is in a molecular form
      (vapor), particulate form (aerosol), or bulk form (liquid). The energy content of
      gas stream is the sum of the sensible heat (temperature) of the air and any water
      droplets in it and the heat of vaporization (latent energy) of any water vapor
      present. Latent heat energy is much larger than sensible heat energy, so
      saturated air contains much more energy than dry air. Thus every breath contains
      a water volume and energy (thermal) challenge to the airway mucosa. When the
      challenge exceeds the homeostatic mechanisms airway dysfunction begins, starting
      at the cellular and secretion level and progressing to whole airway function. A
      large challenge will result in quick progression of dysfunction. Early
      dysfunction is generally reversible, however, so large challenges with short
      exposure times may not cause irreversible injury. The mechanisms of airway injury
      owing to excess water are not well studied. The observation of its effects lends
      itself to some general conclusions, however. Alterations in the ventilation
      perfusion ratio, decrease in vital capacity and compilance, and atelectasis are
      suggestive of partial or full occlusion of small airways. Changes in surface
      tension and alveolar-arterial oxygen gradient are consistent with flooding of
      alveoli. There also may be osmotic challenges to mucosal cell function as
      evidenced by the different reaction rates with hyper- and hypotonic saline. The
      reaction to nonisotonic saline also may partly explain increases in specific
      airway resistance. Aerosolized water and instilled water may be hazardous because
      of their demonstrated potential for delivering excessive water to the airway.
      Their use for airway humidification or toilet should be eliminated or minimized.
      Water vapor is the best form of humidification because it is unlikely to deliver
      sufficient water to cause pulmonary injury. The mechanisms of thermal injury in
      epidermal cells have been well studied, although specific observations of injury
      mechanisms in the airway are sparse. The findings of the epidermal studies can
      readily be applied to airway mucosal cells, however. This work demonstrates that
      it is prudent to avoid raising the average tracheal mucosal temperature above
      approximately 43 degrees C to 45 degrees C. Thus respiratory gases that arrive at
      the tracheal end of the endotracheal tube should average less than 43 degrees C
      to 45 degrees C and 100% RH. It should be noted that to deliver temperatures of
      this magnitude in the trachea would require higher gas temperatures at the
      circuit wye. These temperatures are much greater than the upper temperature
      limits imposed on humidifiers by international standards. Additionally, the
      reports to date of pulmonary thermal injury associated with humidifiers have been
      solely as the result of equipment malfunction or misuse--a situation that is
      increasingly less likely to occur with the control and monitoring features of
      modern devices. In summary, to avoid the injurious effects of excess heat and
      water in the airway, inspiratory gases should be delivered to the patient's
      airway at core temperature and 100% RH. This gas condition is the only one that
      is neutral to the airway mucosa and poses no water volume and heat energy
      challenge. Humidifiers, however, do not measure the gas temperature at the
      patient airway but only at the circuit wye. To compensate for any cooling of the
      gas as it passes from the wye to the patient the gas temperature at the wye must
      be set higher than core temperature. To safely avoid the risk that this higher
      temperature may accidentally reach the patient and cause an injury, the average
      gas temperature at the wye should restricted to less than 43 degrees

PMID- 9648184
TI  - Measuring temperature and humidity in the breathing circuit.
AB  - Accurate measurement of temperature and humidity in the breathing circuit can be
      a difficult task. This article introduces basic humidity concepts, outlines the
      problems that are unique to the breathing circuit, and describes the various
      methods that are available to measure temperature and humidity. Recommendations
      are made on how to measure temperature and humidity in four commonly encountered
      situations.

PMID- 9648185
TI  - Heated humidifiers. Structure and function.
AB  - Humidity in the form of molecular water vapor is an essential requirement for
      intubated patients, and can be beneficial to nonintubated patients receiving CPAP
      or oxygen therapy. There are many different types of humidification devices but
      they generally consist of a humidity generator (or water reservoir) and humidity
      delivery system (or breathing circuit). Humidifiers that generate aerosols may
      provide adequate humidity, but they also provide a transport mechanism for
      contaminants and may deliver excess water to the airways. An ideal system
      generates the required amount of humidity, in the form of water vapor, at the
      correct temperature, and transports it to the patient without the loss of either
      heat or moisture. The most effective way to achieve this is to use a large heated
      water surface for the generator, and heating elements within the delivery system
      to prevent condensation. This system can be configured to provide optimal
      humidity for both intubated and nonintubated patients from the neonatal to the
      adult intensive care unit. Heated humidifiers have no contraindications and can
      be used on any patient requiring ventilatory assistance or supplemental oxygen.

PMID- 9648186
TI  - Heat and moisture exchangers. Structure and function.
AB  - A bewildering array of HMEs are available, suited to many different tidal volume
      and other clinical requirements. Choosing among the different devices depends on
      many attributes. Grouping different HMEs together to describe their performance
      may be inappropriate. Independent tests on HMEs provide information to help when
      choosing among different devices, but care should be exercised to prevent
      inappropriate comparisons being made between results from studies using different
      test procedures and protocols. The use of filters in anesthesia is recommended in
      some countries. Some HMEs have a high moisture-conserving performance, but the
      use of HMEs may be inappropriate for some patient groups, and other humidifying
      devices may be more suitable.

PMID- 9648187
TI  - Humidification during anesthesia.
AB  - Humidification during anesthesia is important to prevent adverse changes in the
      upper airways and possible pulmonary compromise. These changes may take place in
      less than 1 hour using dry nonhumidified anesthetic gases. Consequently, some
      method of humidification should be employed for all but the shortest of surgical
      procedures requiring general anesthesia. Methods of humidification include the
      anesthesia breathing system itself, passive humidification or conservation of
      moisture (the use of HMEs), and active humidification. The simplest system
      providing good levels of humidification and warming of anesthetic gases is the
      Circle system, which uses a fresh gas flow of less than 2 L/min. Its success can
      be further enhanced by use of a coaxial circuit. The minimum levels of water
      output or humidity required in the breathing circuit remain controversial. It may
      be preferable to have a gas with a lower temperature and higher relative humidity
      because a warmer gas that is less saturated may result in increased desiccation
      from the upper airways. Humidification for neonatal and pediatric patients
      requires special consideration of resistance, work of breathing, and dead space.
      Further work is necessary with regard to the use of HMEs in this population of
      patients undergoing general anesthesia.

PMID- 9648188
TI  - Humidification practices in the Adult Intensive Care Unit, Prince of Wales
      Hospital.
AB  - In the Adult Intensive Care Unit of The Prince of Wales Hospital, Sydney,
      Australia, inspiratory gas is humidified to saturation at 37 degrees C. This
      stops the buildup of dried sputum within the endotracheal tubes and thus prevents
      blocked tubes and the increased resistance caused by partial obstruction.
      Inspiratory and expiratory hose heater wires are used to produce a completely dry
      circuit, allowing the elimination of water traps and circuit support arms without
      the resistance of a heat and moisture exchanger.

PMID- 9648189
TI  - Humidification in the intensive care unit.
AB  - In summary, current data indicate that body temperature cannot be controlled
      efficiently by changing inspired gas temperature. Inspired gas temperature should
      therefore be maintained at 32 degrees C to 34 degrees C for intubated patients
      and other efforts should be made to optimize body temperature.

PMID- 9648190
TI  - What is optimum humidity?
AB  - The relevant aspects of the normal physiology of the airway mucosa and the
      customary ways of describing humidity are briefly reviewed. The need for
      surrogate markers of optimum humidity is identified, and two such markers are
      proposed. The relationship between the humidity of the inspired gas and mucosal
      function is examined using a model that is then validated. Optimum humidity is
      achieved when the inspired gas is at body core temperature and 100% relative
      humidity.

PMID- 9648191
TI  - The role of filtration during humidification.
AB  - Nosocomial pneumonia remains an important problem in patients undergoing
      mechanical ventilation, being associated with high mortality and morbidity and
      considerable expenditure. In the past respiratory equipment has been implicated
      in the development of nosocomial pneumonia and strict recommendations for
      cleaning and maintenance have been practiced. It is now known that the circuit
      and other equipment rapidly become contaminated with microorganisms originating
      from the patient's upper airway flora. These organisms access the circuit through
      suctioning and coughing, and may contaminate distant sites by traveling in
      association with aerosols or condensate. Current evidence suggests that circuit
      contamination usually is a result rather than a cause of airway colonization and
      does not have an important role in the pathogenesis of nosocomial pneumonia.
      Provided that reasonable infection control measures are taken, circuit
      contamination does not pose a risk to the ventilated patient. Although bacterial
      filters placed in the circuit effectively prevent circuit contamination they do
      not significantly reduce the incidence of nosocomial pneumonia in patients
      receiving mechanical ventilation.

PMID- 9648192
TI  - Treatment of fracture and complication of cervical spine with ankylosing
      spondylitis.

PMID- 9648193
TI  - Locomotor pattern in paraplegic patients: training effects and recovery of spinal
      cord function.
AB  - Recent studies have shown that a locomotor pattern can be induced and utilized by
      paraplegic patients under conditions of body unloading using a moving treadmill.
      The present study investigated the behaviour of the locomotor pattern and also
      the relationship of its development to the spontaneous recovery of spinal cord
      function assessed by clinical and electrophysiological (tibial nerve
      somatosensory evoked potentials and motor evoked potentials) examinations. The
      earliest time that spinal locomotor activity could be induced was when signs of
      spinal shock had disappeared. This activity was distinct from spinal stretch
      reflex activity. In complete paraplegic patients the locomotor pattern improved
      spontaneously without training. This was coincident with both an increase of
      gastrocnemius electromyographic activity during the stance phase of gait and a
      decrease of body unloading. These effects reached a plateau after about 5 weeks.
      In complete and incomplete paraplegic patients a near linear increase of
      gastrocnemius electromyographic activity occurred during the stance phase of a
      step cycle with daily locomotor training over the whole training period of 12
      weeks. This was also coincident with a significant decrease of body unloading. In
      contrast to this, neither clinical nor electrophysiological examination scores
      improved after the onset of training in both patient groups. Only in incomplete
      paraplegic patients was there recovery, albeit statistically insignificant, of
      spinal cord function according to the sensory and motor scores obtained in the
      neurological examination during the time period before onset of training. An
      improvement of locomotor function by training was also seen in patients with
      paraplegia due to a cauda lesion. Such training effects on muscles and tendons
      could be separated from those on the spinal locomotor centres. The findings of
      this study may be relevant for the future clinical treatment of paraplegic
      patients.

PMID- 9648194
TI  - Lateral approach of the dog brachial plexus for ventral root reimplantation.
AB  - A lateral surgical approach of the cervical spinal cord and brachial plexus was
      developed in nine dogs for avulsion and reimplantation of the ventral cervical
      spinal roots (C). The surgical steps involved in exposing the spinal cord and
      roots are described. The avulsed rootlets of C6 and C7 were reimplanted in their
      initial position. As a direct consequence of the avulsion, flaccid paralysis of
      the shoulder and severe amyotrophy developed within 5-7 weeks on the injured
      side. In addition, the dogs exhibited clinical signs resulting from damage to
      long fiber tracts due to the reimplantation procedure. A partial recovery of
      these deficits was observed during the 6 postoperative months. Retrograde axonal
      tracing with horseradish peroxidase applied to the distal stump of the
      musculocutaneous, suprascapular, and subscapular nerves (originating from C5, C6
      and C7) revealed the presence of labelled neuronal somata that were located in
      the ipsilateral ventral horn, close to the tip of the reimplanted rootlets. It is
      concluded that the dog constitutes a worthwhile animal model for the study of
      avulsion and reimplantation of brachial plexus root via a lateral surgical
      approach.

PMID- 9648195
TI  - Cervical myeloradiculopathy with entrapment neuropathy: a study based on the
      double-crush concept.
AB  - In an attempt to formulate a standardised approach to the diagnosis and
      management of patients with the double-crush syndrome, we reviewed 65 surgical
      cases (39 men and 26 women) with cervical myeloradiculopathy associated with
      entrapment neuropathy in the arm by examining the clinical features, results of
      nerve conduction velocity studies and distribution of the vertebral levels of
      compression. Fifty-three patients (average age, 43 years) presented with a carpal
      tunnel syndrome at the wrist and cervical lesions (41 with spondylosis and 12
      with ossified posterior longitudinal ligament), while 12 had a cubital tunnel
      syndrome at the elbow with cervical lesions (eight with spondylosis and four with
      ossification of the posterior longitudinal ligament). In the former group, the
      lesions were found mostly at C5-6 and C6-7 levels, while in the latter group
      involvement of C6-7 was frequently observed. Two patients in each group required
      additional cervical decompression after carpal or cubital tunnel release. A
      retrospective review of our patients suggested that it is reasonable to pursue an
      accurate diagnosis followed by treatment based on individual neurological and
      electrophysiological findings, but taking into consideration the significant
      level of physical impairment associated with cord compromise, we believe that it
      may be reasonable to perform a cervical decompression rather than peripheral
      nerve release in such cases. Our findings suggest that one should be aware of a
      double-crush during examination of patients complaining of neck and hand
      problems.

PMID- 9648196
TI  - Factors associated with contractures in acute spinal cord injury.
AB  - The purpose of this study was to examine the occurrence of contractures in acute
      SCI and clarify possible contributing factors such as early versus late
      admission, level of injury, completeness of the lesion, pressure ulcers,
      spasticity, co-existent head injury, extremity fractures, heterotopic
      ossification (HO), peripheral nerve injury, and shoulder pain. The records of all
      patients (n = 482) admitted between 1990 and 1995 with acute SCI to a model SCI
      system were reviewed. Of 482 patients 44 (9%) (33 male, 11 female) developed
      contractures during their initial hospitalization. There were 30 tetraplegic and
      14 paraplegic patients. Thirty-four patients had complete and 10 patients had
      incomplete lesions. The percentage of occurrence of contractures among patients
      admitted to the model system on the day of injury was 7.6% and among those
      admitted between 2 and 60 days of the injury was 15% (P = 0.05). Patients with a
      pressure ulcer (14.1%) were significantly more likely to have a contracture than
      patients without a pressure ulcer (7.1%) (P = 0.05). Contractures were also more
      common in patients with spasticity requiring medication; 12.7% of patients with
      spasticity compared to 7.8% without spasticity, had contractures (P < 0.05).
      Patients with a co-existent or suspected head injury (15%) were more likely to
      have contractures than patients without it (7.4%)(P < 0.05). Eighteen patients
      with a contracture had HO, extremity fracture, peripheral nerve injury or reflex
      sympathetic dystrophy. In conclusion, this study is one of the first to
      demonstrate a significant association of contractures in acute SCI with pressure
      ulcers and co-existent head injury and reaffirms the importance of early
      admission to a coordinated SCI center in the prevention of contractures.

PMID- 9648197
TI  - Effect of intermittent urethral catheterization and oxybutynin bladder
      instillation on urinary continence status and quality of life in a selected group
      of spinal cord injury patients with neuropathic bladder dysfunction.
AB  - OBJECTIVES: A comparative assessment of (i) urinary continence status, (ii)
      quality of life, and (iii) sexuality in spinal cord injury patients prior to, and
      during intermittent catheterization with adjunctive intravesical oxybutynin
      therapy (Cystin: manufactured by Leiras Oy. Helsinki, Finland). SETTING: A
      hospital, and community-based study of selected adult, male, spinal cord injury
      patients registered with the Regional Spinal Injuries Centre, Southport.
      PATIENTS: Seven patients (mean age: 44.3 years) suffering from neuropathic
      bladder due to suprasacral spinal cord lesion of traumatic aetiology, and well
      settled in the community in the north-west of England were the subjects of this
      study. Before commencing the intermittent catheterization regime, these patients
      were on penile sheath drainage. INTERVENTION: Intermittent urethral
      catheterization was performed with sterile, single-use Nelaton catheters 5-6
      times a day with intravesical instillation of oxybutynin 5 mg in 30 ml. 1-3 times
      a day for periods ranging from 14 to 30 months. OUTCOME MEASURES: Assessment of
      urinary continence, sexuality, and quality of life was made (i) at the outset
      before any intervention, (ii) during intermittent catheterization regime, and
      (iii) when the patients were using the oxybutynin bladder instillation along with
      intermittent catheterization. RESULTS: Initially all the seven patients were
      constantly wearing penile sheaths and leg bags. When these patients performed
      intermittent catheterization 5-6 times in 24 h, they attempted to discard the
      penile sheath during the day but they were experiencing mild to moderate urine
      leak between catheterization. They were compelled to wear penile sheaths during
      night. Subsequently, five patients took oxybutynin by mouth, but developed an
      unacceptable degree of side-effects necessitating discontinuation of the
      medication. Following commencement of intravesical oxybutynin therapy, all of
      them were able to discard the penile sheaths and leg bags during the day as well
      as during the night. However, on waking-up after a full night's sleep, three
      patients found dampness of their undergarments 1-2 times per week. None of the
      patients experienced side-effects attributable either to the intermittent
      catheterization procedure, or to the intravesical oxybutynin therapy. The number
      of episodes of urinary infection requiring antibiotic therapy was
      0.08/patient/month. All the seven patients noticed a remarkable improvement in
      the quality of life because they had achieved a high degree of continence. All
      the seven patients commented on the improved sense of their own sexuality which
      was attributed to (i) absence of incontinence episodes, (ii) improved self-image,
      and (iii) not wearing penile sheaths and leg bags. CONCLUSION: These seven spinal
      cord injury patients achieved socially acceptable continence with improved
      quality of life, and enhanced sexuality with the intermittent urethral
      catheterization regime and intravesical oxybutynin therapy.

PMID- 9648198
TI  - Camel collision as a major cause of low cervical spinal cord injury.
AB  - One hundred and forty patients with low cervical spinal cord injuries, who were
      admitted to the Riyadh Armed Forces Hospital over the past 10 years were
      reviewed. Motor vehicle accidents constituted 119 (85%) of the patients. Camel
      collisions were a major cause of vehicle accidents 39 (33%), after rollover
      accidents 70 (59%), and much more than head on collisions 9 (7.5%). Male to
      female ratio was 14:1 with a mean age of 32 years. Camel collision although a
      commonly observed cause of motor vehicle accidents in the Middle East has not
      been mentioned in the literature before. The mechanism of injury is not much
      different, but the exact description of the accident and sustaining injury is
      interesting because it leads to localised damage to the neck without major body
      trauma and mortality.

PMID- 9648199
TI  - Shoulder and elbow motion during two speeds of wheelchair propulsion: a
      description using a local coordinate system.
AB  - Individuals who propel wheelchairs have a high prevalence of upper extremity
      injuries. To better understand the mechanism behind these injuries this study
      investigates the motion of the shoulder and elbow during wheelchair propulsion.
      The objectives of this study are: (1) To describe the motion occurring at the
      shoulder and elbow in anatomical terms during wheelchair propulsion; (2) to
      obtain variables that characterize shoulder and elbow motion and are
      statistically stable; (3) to determine how these variables change with speed. The
      participants in the study were a convenience sample of Paralympic athletes who
      use manual wheelchairs for mobility and have unimpaired arm function. Each
      subject propelled an ultralight wheelchair on a dynamometer at 1.3 and 2.2 meters
      per second (m/s). Biomechanical data was obtained using a force and moment
      sensing pushrim and a motion analysis system. The main outcome measures
      investigated were: maximum and minimum angles while in contact with the pushrim,
      range of motion during the entire stroke and peak accelerations. All of the
      measures were found to be stable at both speeds (Cronbach's alpha > 0.8). The
      following measures were found to differ with speed (data format: measure at 1.3
      m/s +/- SD; measure at 2.2 m/s +/- SD): minimum shoulder abduction angle during
      propulsion (24.5 degrees +/- 6.7, 21.6 degrees +/- 7.2), range of motion during
      the entire stroke in elbow flexion/extension (54.0 degrees +/- 9.9, 58.1 degrees
      +/- 10.4) and shoulder sagittal flexion/extension (74.8 degrees +/- 9.4, 82.6
      degrees +/- 8.5), and peak acceleration in shoulder sagittal flexion/extension
      (4044 degrees/s2 +/- 946, 7146 degrees/s2 +/- 1705), abduction/adduction (2678
      degrees/s2 +/- 767, 4928 degrees/s2 +/- 1311), and elbow flexion/extension (9355
      degrees/s2 +/- 4120, 12889 degrees/s2 +/- 5572). This study described the motion
      occurring at the shoulder and elbow using a local coordinate system. Stable
      parameters that characterize the propulsive stroke and differed with speed were
      found. In the future these same parameters may provide insight into the cause and
      prevention of shoulder and elbow injuries in manual wheelchair.

PMID- 9648200
TI  - Reliability of a tool for assessing mobility in wheelchair-dependent paraplegics.
AB  - The aim of this study was to design and test the reliability of an assessment
      tool that could be used by physiotherapists to quantify the mobility of
      wheelchair-dependent paraplegics. The assessment tool examined six key tasks
      fundamental to the mobility of wheelchair-dependent paraplegics, comprising
      moving from lying to sitting, completing a horizontal transfer, completing a
      vertical transfer, pushing on flat ground, pushing on ramps and negotiating
      kerbs. A six-point scoring system was used to assess the level of mobility
      attained by subjects on each task. The scoring system was different for each task
      and took into account the level of assistance and time required to complete the
      task or the complexity of the task. Twenty wheelchair-dependent paraplegics were
      assessed independently by two therapists using the assessment tool. The Cohen's
      Weighted Kappas describing inter-rater reliability of each task ranged between
      0.82-0.96, indicating a high reliability between therapists. It was concluded
      that the assessment tool is a reliable way of assessing the mobility of
      wheelchair-dependent paraplegics.

PMID- 9648201
TI  - Post traumatic paraplegics living in Athens: the impact of pressure sores and
      UTIs on everyday life activities.
AB  - This paper contains the findings of a scientific research which was done on post
      traumatic paraplegics who live in the area of Athens. Greece, and measured the
      impact of pressure sores and UTIs on their everyday life activities. The target
      population was 127 individuals out of which 98 were observed and interviewed. A
      semi-structured questionnaire which consisted of two parts used; the first part
      of the questionnaire included general questions whereas the second contained the
      Sarno Functional Life Scale (SFLS) which is a tool measuring the level of
      independence of disabled people. Sixty-two per cent of the population was male.
      The mean age of the sample population at the time they had the accident which
      caused the paraplegia was 31.5, while the median was 28.5. The majority of the
      subjects comes from the lower socioeconomic class. Traffic accidents accounted
      for the 55% of the occurrences of paraplegia, falls for 37%, surgical
      complication for 4% and athletic activities for the remaining 4%. Forty-nine
      percent of the sample had been hospitalised in a rehabilitation centre. However,
      the multiple regressions used did not reveal any statistically significant
      relation between the hospitalisation in a rehabilitation centre and the
      paraplegic's scores in any of the Sarno Functional Life Scale's (SFLS) variables.
      Instead, the multiple regressions employed yielded paraplegics' scores in the
      SFLS's everyday life activities that were negatively related to age (P = 0.004)
      and pressure sores (P = 0.021). The paraplegics' scores on the SFLS's indoors
      activities are positively related to the years since injury (P = 0.048) and
      health education on daily fluid consumption (P = 0.003). The scores of the
      subjects on the SFLS's outdoor activities are positively related to the years of
      education (P = 0.008), the years since injury (P = 0.011), while are negatively
      related to pressure sores (P = 0.034) and UTIs (0.044). The subjects' scores on
      the SFLS variables regarding social relations had a negative relation to sex,
      (female) (P = 0.0001), age (P = 0.001) and pressure sores (P = 0.019), while they
      have a positive relation with the years since injury (P = 0.024).

PMID- 9648202
TI  - Spinal cord injury management in Salisbury: the history of the Duke of Cornwall
      Spinal Treatment Centre.
AB  - One point remains paramount in our minds and that is, in order to achieve the
      goals we have set, we need vigorously to ensure that Spinal Units continue to be
      seen as the only facilities competent to provide for the diverse needs of spinal
      cord injured patients. We at the Duke of Cornwall Spinal Treatment Centre are
      fortunate in having a first class, expanding facility and have the tireless
      cooperation of both our staff and those of the other departments in Salisbury. We
      recognize also that we can play a leading role in the treatment of patients, not
      only from the Southwest, but, where and when appropriate, from further afield.

PMID- 9648203
TI  - Neuromuscular electrical stimulation keeps a tetraplegic subject in his chair: a
      case study.
AB  - Pressure ulcers are an important complication of spinal cord injury which place
      an enormous burden on society due to their financial, psychosocial, and
      vocational implications. Although they are now rarely fatal, they can still have
      devastating consequences, often needing prolonged hospitalisation to be properly
      managed. This study reviews the use of electrical stimulation to overcome
      increasing debility due to sacral pressure ulcers and saddle soreness in a man
      with tetraplegia. After 24 months of regular cyclic stimulation he had increased
      circumferential dimensions across his buttocks by up to 21%, and increased his
      sitting tolerance.

PMID- 9648204
TI  - A review of the respiratory management of a patient with high level tetraplegia.

PMID- 9648205
TI  - Heat capacities of amino acids, peptides and proteins.
AB  - The heat capacity is one of the fundamental parameters describing thermodynamic
      properties of a system. It has wide applications in a number of areas such as
      polymer chemistry, protein folding and DNA stability. To aid the scientific
      community in the analysis of such data, I have compiled a database on the
      experimentally measured heat capacities of amino acids, polyamino acids,
      peptides, and proteins in solid state and in aqueous solutions.

PMID- 9648206
TI  - Effects of metal binding affinity on the chemical and thermal stability of site
      directed mutants of rat oncomodulin.
AB  - Tryptophan fluorescence was used to study the stability and unfolding behavior of
      several single tryptophan mutants of the metal-binding protein rat oncomodulin
      (OM); F102W, Y57W, Y65W and the engineered protein CDOM33 which had the 12
      residues of the CD loop replaced with a more potent metal binding site. Both the
      thermal and the chemical stability were improved upon binding of metal ions with
      the order apo < Ca2+ < Tb3+. During thermal denaturation, the transition
      midpoints (T(un)) of Y65W was the lowest, followed by Y57W and F102W. The
      placement of the Trp residue in the F-helix in F102W made the protein slightly
      more thermostable, although the fluorescence response was readily affected by
      chemical denaturants, which acted through the disruption of hydrogen bonds at the
      C-terminal end of the F-helix. Under both thermal and chemical denaturation, the
      engineered protein showed the highest stability. This indicated that increasing
      the number of metal ligating oxygens in the binding site, either by using a metal
      ion with a higher coordinate number (i.e., Tb3+) which binds more carboxylate
      ligands, or by providing more ligating groups, as in the CDOM33 replacement,
      produces notable improvements in protein stability.

PMID- 9648207
TI  - Contributions of solvent-solvent hydrogen bonding and van der Waals interactions
      to the attraction between methane molecules in water.
AB  - The contribution of solvent-solvent hydrogen bonding and van der Waals
      interactions to the attraction between methane molecules in water was
      investigated by comparing the potential of mean force (PMF) between two methane
      molecules in TIP4P water to those in a series of related liquids in which the
      solvent-solvent interactions were progressively turned off while keeping the
      solvent-solute interactions unchanged. The magnitude of the attraction between
      methanes was not significantly changed when the hydrogen bonding interaction
      between solvent molecules was eliminated and the solvent was maintained in the
      liquid state by increasing either the pressure or the magnitude of the solvent
      solvent van der Waals interaction. However, when solvent-solvent excluded volume
      interactions were eliminated, the methane molecules interacted no more strongly
      than in the gas phase. The results are consistent with the idea that the primary
      contribution of hydrogen bonding to the hydrophobic interaction is to keep water
      molecules in a liquid state; at constant density, packing interactions rather
      than hydrogen bonding appear to be critical as suggested by scaled particle
      theories of solvation. The overall shape of the PMF was, however, changed in the
      absence of hydrogen bonding, pointing to an influence of hydrogen bonding on the
      detailed form of the interactions between nonpolar solutes in water. The effects
      of correlations between the configurations sampled during the Monte Carlo
      procedure used in the free energy calculations on the estimation of errors was
      also characterized.

PMID- 9648208
TI  - Near UV circular dichroism from biomimetic model compounds define the
      coordination geometry of vanadate centers in MeVi- and MeADPVi-rabbit myosin
      subfragment 1 complexes in solution.
AB  - The circular dichroism (CD) spectrum was measured from vanadate (Vi) cyclic
      esters of chiral vicinal diols, hydroxycarboxylates, and cyclodextrines as a
      function of Vi concentration ([Vi]) and at the lowest energy transitions of the
      vanadium. At low [Vi] and in the presence of excess vicinal diols,
      hydroxycarboxylates, or cyclodextrines the CD signal intensity scales linearly
      with [Vi] indicating the predominance of a monomeric cyclic ester. At higher
      [Vi], the signal intensity in the presence of the vicinal diols and
      hydroxycarboxylates become nonlinear in [Vi], indicating formation of a dimeric
      cyclic ester. Vanadium-51 NMR (51V-NMR) indicates the coordination geometry of
      several of these model Vi centers in solution and identifies the CD signals
      characteristic to Vi trigonal bipyramidal (tbp) and octahedral (Oh) coordination
      geometries from monomeric and dimeric species. The CD spectra from monomeric and
      dimeric forms of the tbp-coordinated model compounds have two apparent
      transitions with amplitudes of opposite sign at wavelengths > or = 240 nm.
      Spectra from the monomeric and dimeric Oh coordinated species are distinct from
      the tbp-type spectra over the same wavelength domain because of the presence of
      two additional transitions with opposite sign amplitudes. These model spectra
      were compared to the vanadate CD spectra from Vi bound to rabbit myosin
      subfragment 1 (S1) in solution, in the presence of divalent metal cations (MeVi
      S1) or trapped with MeADP (MeADPVi-S1). Polymeric MeVi binds to the active site
      of S1 and the vanadate centers in MnVi-S1 or CoVi-S1 produce a CD signal
      resembling that from the tbp model. The trapped ATPase transition state analog
      MeADPVi produces a different CD signal resembling that from the Oh model.

PMID- 9648209
TI  - Characterization of the interaction between bovine pancreatic trypsin inhibitor
      and thiocyanate by NMR.
AB  - The interaction between Bovine Pancreatic Trypsin Inhibitor and thiocyanate was
      studied using NMR spectroscopy following several experimental approaches. The
      chemical shift variations of the BPTI protons in the absence and in the presence
      of increasing thiocyanate concentrations (up to 0.2 M) were significant (> 0.05
      ppm) for 30 protein protons belonging to 20 residues. The largest deviation, 0.2
      ppm, was observed for the amide backbone proton of Arg42 in the absence of
      thiocyanate and in the presence of 40 molar equivalents of thiocyanate. The
      influence of the presence of thiocyanate on the electrostatic potential
      surrounding the protein was demonstrated by NOESY spectra selective at the water
      frequency: the presence of SCN- favours acid catalysed exchange and disfavours
      base catalysis. However, a specific effect of thiocyanate was pointed out since
      the comparison of the chemical shifts in the presence of 40 molar equivalents of
      KSCN and KCl, respectively, showed much more as well as larger deviations
      compared to measurements in the absence of salt. A dissociation constant, KD, for
      a 1/1 complex between BPTI and thiocyanate was calculated from chemical shifts
      measurements: KD = 89 +/- 8 mM. A second value, KD = 99 +/- 10 mM, was extracted
      from SC15N relaxation time measurements.

PMID- 9648210
TI  - Transient kinetics and thermodynamics of anthroylouabain binding to Na/K-ATPase.
AB  - The Na/K-ATPase is an integral membrane protein enzyme which uses energy derived
      from hydrolysis of ATP to pump Na+ out of and K+ into the cell. Ouabain belongs
      to a class of drugs known as cardiac glycosides, which are useful for treating
      congestive heart failure. Therapeutic value is achieved when these drugs bind to
      and inhibit the Na/K-ATPase of cardiac muscle. We gain insight into this
      important interaction by measuring the thermodynamics of the interaction of
      anthroylouabain (AO), a fluorescent derivative of ouabain, with the Na/K-ATPase.
      AO has the useful property that its fluorescence intensity is greatly enhanced
      (approximately 10x) when it binds to the enzyme. Using this enhancement, we
      measure temperature dependence of transient kinetics for the association and
      dissociation of AO interacting with membrane fragments of Na/K-ATPase purified
      from dog kidney. Using a standard Eyring analysis, we find that the overall
      association of AO with the enzyme is driven by substantial contributions from
      both enthalpy and entropy, and that in an energy diagram for the association
      pathway, the free energy change is quite similar to that of ouabain deduced from
      previously published results [E. Erdmann, W. Schoner, BBA 307 (1973) 386].
      However, in the transition state, there are substantial differences for the
      enthalpy and entropy, presumably due to the presence of the anthracene moiety.

PMID- 9648211
TI  - Increased cellulose production from sucrose with reduced levan accumulation by an
      Acetobacter strain harboring a recombinant plasmid.
AB  - Cellulose production from sucrose by Acetobacter strains is accompanied by the
      accumulation of a water-soluble polysaccharide, called levan. To improve
      cellulose productivity, a levansucrase-deficient mutant, LD-2, was derived from
      Acetobacter strain 757 and used as a host for the construction of recombinant
      strains. An LD-2 mutant harboring a plasmid containing the sucrase gene, sucZE3,
      from Zymomonas mobilis together with zliS, a gene that encodes a secretion
      activating factor under the control of the Escherichia coli lac promoter, had
      sucrase activity and produced much cellulose and little levan in a medium
      containing sucrose. In addition, a mutant levansucrase gene, mutant sacB, from
      Bacillus subtilis, which encodes a protein with little levan-forming activity,
      was generated by site-directed mutagenesis and introduced into the LD-2 mutant.
      This introduction also resulted in the higher cellulose productivity and little
      levan.

PMID- 9648212
TI  - Effects of difructose anhydride III on calcium absorption in small and large
      intestines of rats.
AB  - Difructose anhydride III (DFA III; di-D-fructo-furanose 1,2':2,3' dianhydride)
      was prepared from inulin with Arthrobacter sp. H65-7 inulin fructotransferase
      (depolymerizing (inulase II; EC 2.4.1.93). DFA III is not hydrolyzed by enzymes
      in the small intestine, but is metabolized by microorganisms in the large
      intestine. We investigated the effects of DFA III on calcium absorption in two
      experiments. In the in vivo experiment, we examined the effects of DFA III,
      fructooligosaccharides, and raffinose on calcium absorption in male Sprague
      Dawley rats 5 weeks old at start of the experiment and given feed containing 3%
      of one of these oligosaccharides for two weeks. The apparent calcium absorption
      was significantly higher in rats fed any of these oligosaccharides than in
      control rats, and the increase with DFA III was the greatest. Absorption in both
      the small and large intestines was affected. In rats fed DFA III, the cecal wall
      thickened and soluble calcium and the amounts of some organic acids were higher
      than in the control groups. In an in vitro experiment with everted jejunal and
      ileal sacs of rats, calcium absorption was higher when DFA III was present in the
      mucosal fluid at all concentrations tested (up to 200 mM). In the jejunal sacs,
      the increase in calcium absorption depended on the DFA III concentration. In the
      ileal sacs, the absorption was maximum at 50 mM DFA III and did not increase
      further at higher concentrations. These results indicate that intact DFA III
      stimulates calcium absorption in the small intestine, and that cecal fermentation
      of DFA III may contribute to the increase in calcium absorption by the large
      intestine.

PMID- 9648213
TI  - Physiological role of L-ascorbic acid in rats exposed x887p6arette smoke.
AB  - This study clarifies the effect of exposure to cigarette smoke on L-ascorbic acid
      (AsA) metabolism and on the activities of drug-metabolizing enzymes. Male Wistar
      rats were used. The test rats (group T) were exposed to side-stream smoke from
      cigarette for 2 h every day for 25 days. During the experimental period, the
      excreted amount of AsA in the urine from group T was higher than that from the
      control group (group C). At the end of the experimental period, the AsA content
      of the plasma and tissues, the liver cytochrome P-450 content and the activities
      of drug-metabolizing enzymes in group T were each higher than those in group C.

PMID- 9648214
TI  - Correlation between the drinkability of beer and gastric emptying.
AB  - A subjective evaluation of beer drinkability and the degree of stomach fullness
      were found to correlate with the relaxed cross-sectional area of the pylorus
      antrum measured by real-time ultrasonography. Five kinds of beer with a different
      malt/adjuncts ratio and degree of attenuation were used. Each beer was given to 9
      healthy volunteers at the rate of 3 ml/kg/15 min, and they each recorded the
      degree of stomach fullness, desire to drink and tastiness every 30 min. With
      increasing volume drunk, the degree of tastiness and desire to drink were
      lowered, and the degree of stomach fullness raised. The relaxed cross-sectional
      area of the pylorus antrum measured by an ultrasonic image analyzer every 30 min
      was highly correlated with the degree of stomach fullness, tastiness of the beer,
      and desire to drink (p = 0.0021, < 0.0001, 0.001). The beer giving the lowest
      degree of stomach fullness was appraised to be tasty and highly drinkable. These
      findings suggest that the rate of gastric emptying is one of the factors
      determining the drinkability of beer, and that measurement of the relaxed cross
      sectional area of the pylorus antrum is useful to evaluate stomach fullness
      during beer drinking.

PMID- 9648215
TI  - Isolation, characterization, and sugar chain structure of endoPG Ia, Ib and Ic
      from Stereum purpureum.
AB  - Three endopolygalacturonases (endoPG Ia, Ib, and Ic) were isolated from the
      culture filtrate of Stereum purpureum, the causative fungus of apple silver-leaf
      disease. Their properties, including specific activities, optimum pHs, thermal
      stabilities, and kinetic parameters (K(m) and Vmax) were compared. Their
      properties were very similar to one another except for the substrate specificity
      and relative molecular mass. The sugar chains of endoPG Is were released by
      hydrazinolysis, and one major sugar chain common to endoPG Is was isolated. The
      pyridylamino sugar was characterized by a two-dimensional mapping method using
      HPLC, and identified as a high mannose type N-linked sugar chain, Man alpha 1
      6(Man alpha 1-3)Man alpha 1-6(Man alpha 1-3) Man beta 1-4 GlcNAc beta 1-4 GlcNAc
      (designated as M5.1). Observation of the course of Western blot analysis for the
      proteins from the culture filtrate with endoPG I antibodies showed that the
      fungus secreted three endoPG Is into the culture broth during the growing period.

PMID- 9648216
TI  - Cloning and characterization of the azurin iso-1 gene, concerned with the
      electron transport chain involved in methylamine/methanol oxidation in the
      obligate methylotroph Methylomonas sp. strain J.
AB  - Two azurin-type blue copper proteins, which is concerned with the electron
      transport chain involved in methylamine/methanol oxidation, have been found in
      the obligate methylotroph Methylomonas sp. strain J. The azurin iso-1 gene was
      cloned and sequenced to analyze the role in the electron transport chain. PCR
      products synthesized with primers based on the N- and C-terminal amino acid
      sequences of azurin iso-1 were used as probes for cloning. One complete open
      reading frame (the azurin iso-1 gene) and one partial orf (orf1) were found in a
      cloned Eco105I-HindIII fragment, pMAZ3, with a total of 1066 bp. The gene encoded
      148 amino acid residues. The amino acid sequence after Ala-21, deduced from the
      nucleotide sequence, was identical to that of the azurin iso-1 protein. The gene
      was in a region separate from the mau gene cluster in the chromosome. Escherichia
      coli expressed azurin iso-1. The results of northern blotting analysis suggested
      that expression of the azurin iso-1 gene is regulated by a complex regulatory
      network controlling oxidation of methylamine or methanol in this strain; for
      example, copper ions affected the expression of the azurin iso-1 gene.

PMID- 9648217
TI  - Isolation of Agrobacterium sp. strain KNK712 that produces N-carbamyl-D-amino
      acid amidohydrolase, cloning of the gene for this enzyme, and properties of the
      enzyme.
AB  - Agrobacterium sp. strain KNK712, which produced N-carbamyl-D-amino acid
      amidohydrolase (DCase) was isolated from soil. The bacterium had D-specific
      hydantoinase activity also. Both enzymes are suitable for use in the production
      of D-amino acids. The DCase gene from Agrobacterium sp. strain KNK712 was cloned
      into Escherichia coli. The cloned DNA fragment contained one open reading frame,
      predicted to encode a peptide of 304 amino acids, with a calculated molecular
      weight of 34,285. The DCase gene was overexpressed under the control of the lac
      promoter, and DCase accounted for 50% of the soluble protein in the cells. The
      enzyme was purified and some properties were investigated. Both the optimum pH
      and the pH that gave greatest stability were about pH 7.0. The optimum
      temperature was 65 degrees C, and the enzyme was stable at 55 degrees C. The
      enzyme had strict specificity toward N-carbamyl-D-amino acids, and was inhibited
      by thiol reagents, Cu2+, Hg2+, Ag+, and ammonia.

PMID- 9648218
TI  - Screening, characterization, and cloning of the gene for N-carbamyl-D-amino acid
      amidohydrolase from thermotolerant soil bacteria.
AB  - For the production of D-amino acids, thermotolerant bacteria producing N-carbamyl
      D-amino acid amidohydrolase were isolated from soil by enrichment culture at 45
      degrees C with N-carbamyl-D-amino acids as the sole nitrogen source. The enzyme
      activities and substrate specificities of these strains were examined by the
      resting cells reaction. One of the enzymes, produced by Pseudomonas sp. strain
      KNK003A, was purified and characterized, and the amino acids of its N-terminal
      region were sequenced. A DNA fragment containing the gene for a thermostable N
      carbamyl-D-amino acid amidohydrolase was then cloned into Escherichia coli. The
      gene encoded a peptide of 312 amino acids, with a calculated molecular weight of
      35,000. The similarity of the deduced amino acid sequences of this enzyme and a
      related enzyme from a mesophile, Agrobacterium sp. strain KNK712, was 60%. A
      database was searched for similar sequences.

PMID- 9648219
TI  - Sequence analysis by cloning of the structural gene of gassericin A, a
      hydrophobic bacteriocin produced by Lactobacillus gasseri LA39.
AB  - Gassericin A, a bacteriocin from Lactobacillus gasseri LA39, was purified to
      homogeneity from the culturesupernatant mainly by reverse-phase chromatography.
      The molecular weight of gassericin A was found to be 5,652 by mass analysis,
      unlike the estimated 3,800 found by SDS-PAGE. However, when the purified
      preparation was treated with lysylendopeptidase, it migrated as a single band to
      5,600 with bacteriocin activity on SDS-PAGE. N- and C-terminal amino acids could
      not be identified. The internal amino acid could be identified after gassericin A
      was hydrolyzed with lysylendopeptidase. The DNA of the structural gene of
      gassericin A was sequenced by cloning of the gene from chromosomal DNA with an
      oligonucleotide probe. The structural gene of gassericin A was found on the
      chromosomal DNA as an open reading frame encoding a protein composed of 91 amino
      acids. The amino acid sequence of mature gassericin A was predicted to be 58
      residues from the DNA sequence and results of mass analysis. These results
      suggested that gassericin A has a closed circular structure with N- and C
      terminals linked. Gassericin A is a hydrophobic class II bacteriocin; it was 98%
      identical with acidocin B produced by Lactobacillus acidophilus M46.

PMID- 9648220
TI  - Identification of deoxy-D-fructosyl phosphatidylethanolamine as a non-enzymic
      glycation product of phosphatidylethanolamine and its occurrence in human blood
      plasma and red blood cells.
AB  - The amino-carbonyl reaction (Maillard reaction), also known as glycation, of egg
      yolk phosphatidylethanolamine (PE) was induced by incubating PE (50 mg/ml) with D
      glucose (222 mM) in a methanol medium containing 2,6-ditert-butyl-p-cresol as an
      antioxidant at 37 degrees C for 4 days. The resultant product, glycated PE (gPE),
      was then isolated from the reaction mixture by two-step normal and reversed-phase
      high-performance liquid chromatography with UV diode array detection and was
      characterized as having a 1:1:1 elemental ratio of phosphorus:nitrogen:sugar. The
      Fourier transform-nuclear magnetic resonance spectrum and infrared absorbance
      spectrum indicate the isolated gPE to have been deoxy-D-fructosyl PE, which is an
      Amadori product of PE. The fast atom bombardmentmass spectrometric data for the
      glycation product of authentic dioleoyl PE (1,2-di-9-octadecenoyl-sn-glycero-3
      phosphoethanolamine) show that the molecular weight of gPE corresponds to that of
      glucose-conjugated PE in the form of an Amadori product. This Amadori product
      formation was also confirmed in PE/phosphate buffer dispersions and in
      phosphatidylcholine-PE liposome/phosphate buffer suspensions in the presence of D
      glucose at 37 degrees C. gPE was degraded by phospholipase A2, C and D. Freshly
      spiked blood plasma and red blood cells (RBC) from nomal human volunteers
      contained substantial levels of gPE, the concentration corresponding to at least
      9 mol% of PE. Remarkable formation of gPE, up to 15-45 mol% of PE in human blood
      plasma and RBC, was further confirmed by prolonged incubation with 5-45 mM D
      glucose. The gPE formation in RBC was found to be proportional to the glycated
      hemoglobin formation.

PMID- 9648221
TI  - Effects of rapessed oil on activity of methylmalonyl-CoA carboxyltransferase in
      culture of Streptomyces fradiae.
AB  - To investigate why more tylosin was produced when Streptomyces fradiae T1558 was
      cultured in a rapeseed oil medium than in a glucose or starch medium, we measured
      the activity of methylmalonyl-CoA carboxyltransferase (EC 2.1.3.1) and
      intracellular propionic acid. The activity of the enzyme, which catalyzes the
      formation of the precursor of tylosin, protylonolide, was 0.19 U/mg protein in 5
      days of culture in rapeseed oil medium, which was 2.5- and 1.3-fold that with the
      glucose or starch medium, respectively. The intracellular propionic acid
      concentration was 1.2 g/g of dry weight, which was 4.3- and 2.1-fold that with
      the glucose or starch medium, respectively. The addition of propionic acid
      increased tylosin production in batch culture: when 0.2 g/l (final concentration)
      propionic acid was added to the glucose medium, 3.8 g/l tylosin was produced in
      10 days of culture, 4.7-fold the amount without propionic acid. These findings
      suggest that in glucose medium, intracellular propionic acid is a limiting factor
      because of the low activity of methylmalonyl-CoA carboxyltransferase of the
      tylosin biosynthesis pathway.

PMID- 9648222
TI  - Liberation of phospholipids from Z-disks of chicken skeletal muscle myofibrils by
      0.1 mM calcium ions: weakening mechanism for Z-disks during post-mortem aging of
      meat.
AB  - Weakening of the Z-disks of skeletal muscle myofibrils contributes to the
      tenderization of meat during post-mortem aging. To elucidate the weakening
      mechanism, we compared Z-disks weakened by post-mortem aging of chicken breast
      muscle with those of myofibrils treated with a solution containing 0.1 mM CaCl2
      and 1 microM calpastatin domain I. In both cases, the Z-disks were weakened with
      a corresponding liberation of their constituent phospholipids (PLs). The
      liberation of PLs specific to 0.1 mM calcium ions was minimal at pH 6.5 and
      maximal at 35 degrees C together with the Z-disk weakening. Binding of calcium
      ions to PLs in the Z-disks was determined by 45Ca-autoradiography. Acidic PLs
      were strongly radioactive and neutral PLs were appreciably radioactive. It is
      very probable that acidic PLs would bind electrostatically to alpha-actinin under
      physiological conditions, and that this interaction would be broken by the
      binding of calcium ions at 0.1 mM to PLs, resulting in the partial liberation of
      PLs from Z-disks. We conclude, therefore, that the liberation of PLs by the
      binding of 0.1 mM calcium ions was the main cause for Z-disk weakening during the
      post-mortem aging of chicken.

PMID- 9648223
TI  - Deterioration of connectin/titin and nebulin filaments by an excess of protease
      inhibitors.
AB  - We studied the effect of protease inhibitors at a high concentration on connectin
      and nebulin filaments in myofibrils. Calpastatin domain I at 0.1 mM bound to
      connectin and nebulin filaments, and deteriorated their physico-chemical
      properties; the calcium-binding ability of connectin and nebulin filaments was
      suppressed, the susceptibility of both filaments to trypsin was markedly
      decreased, and the resting tension of mechanically skinned fibers was increased
      by 2.5 times that of the control at a sarcomere length of 3.6 microns. This
      indicates that the connectin filaments were made more rigid. The same phenomenon
      was observed from the treatment of skinned fibers with 1 mM leupeptin whose
      resting tension was increased to 2 times the control value. Microscopically, both
      protease inhibitors induced dense aggregation and disappearance of the regular
      striation of myofibrils due to their non-specific binding to many myofibrillar
      proteins. The use of excess calpastatin domain I and leupeptin should therefore
      be avoided in physiological and biochemical studies on connectin and nebulin
      filaments, as well as on myofibrils.

PMID- 9648224
TI  - Inhibitory effects of lipid oxidation on the activity of plasma lecithin
      cholesterol acyltransferase.
AB  - We investigated the effects of free radical generation on the esterification of
      cholesterol by lecithin-cholesterol acyltransferase (LCAT). A water-soluble free
      radical initiator, 2,2'-azobis-amidinopropane dihydrochloride (AAPH), inhibited
      the activity of plasma LCAT as a function of the incubation time after its
      addition. When a small amount of oxidized HDL was added to plasma, LCAT activity
      was dose-dependently inhibited. To identify the effects of HDL oxidation on LCAT
      activity, a purified enzyme and cofactor in a vesicle solution (an artificial
      substrate) were used. i) LCAT activity was inhibited by the oxidation of
      substrate vesicles, this inhibition being related to the degree of oxidation. ii)
      This inhibition was observed even if apolipoprotein A-I was not oxidized. iii)
      Oxidized phosphatidylcholine, but not oxidized cholesterol, in the vesicles
      affected LCAT activity. iv) The addition of 0-40% of oxidized vesicles to normal
      substrate vesicles resulted in the activity of LCAT being inhibited in a dose
      dependent manner. These results suggest that the esterification of cholesterol by
      LCAT may be affected by the oxidation of substrate phosphatidylcholine via free
      radical generation in the plasma.

PMID- 9648225
TI  - Complexes of serine acetyltransferase and isozymes of cysteine synthase in
      spinach leaves.
AB  - Polyclonal antibodies against cysteine synthase (CSase; EC 4.2.99.8) isozymes 1,
      2, and 3 were used for the detection of complexes of these isozymes with serine
      acetyltransferase (SATase; EC 2.3.1.30). SATase was partially purified and found
      to complex with these isozymes by western blotting and immunotitration. When the
      complexes were treated with a high concentration of O-acetyl-L-serine, they did
      not dissociate. However, some complexes with CSase 1 or 3 dissociated when left
      for 24 h at 4 degrees C. Results of western blotting on SDS-PAGE showed that
      CSase 2 complexed with SATase. CSases 1, 2, and 3 all could complex with SATase,
      but the tightness of the bond differed.

PMID- 9648226
TI  - Direct formation of human interleukin-11 by cis-acting system of plant virus
      protease in Escherichia coli.
AB  - To produce a large amount of recombinant proteins in Escherichia coli, we
      constructed a unique cis-acting expression system using a plant virus protease.
      This new expression system could directly produce recombinant proteins, that had
      a biologically active form. A gene of nuclear inclusion-a (NIa), which had a
      specific amino acid sequence, was fused with a foreign protein gene at the same
      protein reading frame. One of the NIa-specific cleavage amino acid sequences, Gln
      Ala, was also contained at the protein-protein junction. In the case of human
      interleukin-11 (hIL-11), a 23-kDa specific signal band was obtained from
      recombinant bacteria. N-terminal sequencing of the 23-kDa protein showed that NIa
      specifically cleaved the fusion protein at Gln-Ala, producing Ala-hIL-11.
      Furthermore, we could produce the mature rhIL-11 by extending the culture time.
      This 23-kDa protein had the same biological activity as hIL-11 in a mouse
      plasmacytoma, T1165. Combined with fermentation control, we produced mature rhIL
      11 in E. coli.

PMID- 9648227
TI  - Chemical modifications of momordin-a and luffin-a, ribosome-inactivating proteins
      from the seeds of Momordica charantia and Luffa cylindrica: involvement of
      His140, Tyr165, and Lys231 in the protein-synthesis inhibitory activity.
AB  - Effects of chemical modifications on the protein-synthesis inhibitory (PSI)
      activities of momordin-a and luffin-a were investigated. Treatment with a 50-fold
      excess of diethylpyrocarbonate at pH 6.5 modified one histidine residue in
      momordin-a and luffin-a and reduced their PSI activities to 10% and 8.3%,
      respectively. Modifications with a 20-fold excess of KI3 at pH 7.0 at 0 degree C
      greatly reduced their PSI activities to 10% by iodination of nearly one tyrosine
      residue. The PSI activity of momordin-a was rapidly reduced to 6.4% by the
      modification of one lysine residue with trinitrobenzensulfonic acid as in the
      case of luffin-a reported previously. By analyses of the tryptic peptides from
      the modified momordin-a and luffin-a, the modified residues were identified as
      His140, Tyr165, and Lys231. Furthermore, the amounts of three modified momordin-a
      binding to rat liver ribosomes were reduced to about half or less than half of
      that of native momordin-a. From these results, it was suggested that His140,
      Tyr165, and Lys231 are highly exposed on the surface of momordin-a and luffin-a
      molecules and are involved in their PSI activities, probably by binding to
      ribosomes.

PMID- 9648228
TI  - Low sucrase activity in the small intestine of a senescence-accelerated strain of
      mouse, SAMP1.
AB  - The small intestinal sucrase activity in a senescence-accelerated strain of
      mouse, SAMP1, was significantly lower than that in other strains, including its
      control strain, SAMR1. In contrast, the activity of isomaltase, which usually
      associates with sucrase to form a complex enzyme (SI complex), in SAMP1 was
      comparable to that in other strains. Thus, the ratio of the sucrase to isomaltase
      activities (S/I ratio) in SAMP1 was very low (about 0.15), compared with that in
      other strains (around 0.7). The S/I ratio in SAMP1 was abnormally low, even at a
      young age, indicating that senescence did not result in the low sucrase activity.
      Western blot analysis suggests that a large part of the isomaltase subunit
      occurred alone without the association of the sucrase subunit in this strain. In
      contrast, Northern blot analysis shows that the level of mRNA for the SI complex
      in SAMP1 was comparable to that in SAMR1. When the pancreatico-biliary ducts were
      ligated in SAMP1 to reduce the level of pancreatic proteases, a remarkable
      increase was observed in the sucrase activity, whereas the isomaltase activity
      was increased to a much smaller extent. This marked increase in sucrase activity
      resulted in the S/I ratio increasing to 0.84 18 h after the ligation. These
      results suggest the sucrase subunit of the SI complex to be abnormally unstable
      against pancreatic proteases in SAMP1.

PMID- 9648229
TI  - Antimutagenicity of flavones and flavonols to heterocyclic amines by specific and
      strong inhibition of the cytochrome P450 1A family.
AB  - We found the mechanism in flavonoids that can strongly suppress the mutagenicity
      of one of the food-derived and carcinogenic heterocyclic amines, 3-amino-1-methyl
      5H-pyrido[4,3-b]indole (Trp-P-2). The antimutagenicity was evaluated by IC50
      value, the amount required for 50% inhibition of the mutagenicity of 0.1 nmol Trp
      P-2, with Salmonella typhimurium TA98 strain in the presence of S9 mix. The
      flavones and flavonols were two orders stronger as antimutagens that such
      antimutagenic phytochemicals as chlorophylls and catechins. We had previously
      found flavonoids to be a desmutagen to neutralize Trp-P-2 before or during attack
      of DNA, because they had no effect on either the ultimate mutagenic form of Trp-P
      2 (N-hydroxy-Trp-P-2) or the mutated cells. The desmutagenicity of the flavonoids
      did not depend on the hydroxy number or position that should be associated with
      antioxidative potency, and was also unaffected by the solubility of Trp-P-2 in
      the assay solution. The inhibitory effect of the flavonoids on the metabolic
      activation of Trp-P-2 to N-hydroxy-Trp-P-2 was almost in parallel with the
      antimutagenic IC50 value, when determined with a Saccharomyces cerevisiae AH22
      cell simultaneously expressing both rat cytochrome P450 1A1 and yeast reductase.
      The Ki values of flavones and flavonols for the enzyme were less than 1 microM,
      while the K(m) value of Trp-P-2 was 25 microM. The antimutagenicity of the
      flavones and flavonols was thus concluded to be due to inhibition of the
      activation process of Trp-P-2 by P450 1A1 to the ultimate carcinogenic form. They
      were also able to act as antimutagens toward other indirect mutagens that were
      activated by P450 1A1.

PMID- 9648230
TI  - Rice bifunctional alpha-amylase/subtilisin inhibitor: characterization,
      localization, and changes in developing and germinating seeds.
AB  - A bifunctional alpha-amylase/subtilisin inhibitor (RASI) was purified to
      electrophoretic homogeneity from rice (Oryza sativa L.) bran. Its molecular mass
      was 21 kDa by SDS-PAGE and its isoelectric point was 9.05. Purified RASI
      inhibited subtilisin Carlsberg strongly and inhibited alpha-amylase from
      germinating rice seeds weakly. It inhibited rice alpha-amylase more than barley
      alpha-amylase, and the inhibition of rice alpha-amylase was greater at higher
      pHs. RASI did not inhibit trypsin, chymotrypsin, cucumisin, or mammalian alpha
      amylase. The RASI was in the outermost part of the rice grain and its subcellular
      site seemed to be aleurone particles in aleurone cells. SDS-PAGE and western
      blotting showed that RASI was synthesized in the late milky stage in developing
      seeds, and it remained fairly constant during the first 7 days of germination.

PMID- 9648231
TI  - Salicylic acid induces a cytosolic Ca2+ elevation in yeast.
AB  - Cytosolic free calcium ion concentration ([Ca2+]cyt) after a salicylic acid (SA)
      stimulus was monitored in cells of the yeast Saccharomyces cerevisiae expressing
      apoaequorin, which constitutes a Ca(2+)-sensitive luminescent protein, aequorin,
      when combined with coelenterazine. SA induced a transient [Ca2+]cyt elevation
      that was dependent on the concentration of SA and pH of the SA solution. The SA
      induced [Ca2+]cyt elevation was not reduced in Ca(2+)-deficient medium,
      suggesting that Ca2+ was mobilized from an intracellular Ca2+ store(s). Benzoic
      acid, butyric acid and sorbic acid did not induced a [Ca2+]cyt elevation.

PMID- 9648233
TI  - Effectiveness of polyclonal and monoclonal antibodies prepared for an immunoassay
      of the etofenprox insecticide.
AB  - Two polyclonal antibodies and three monoclonal antibodies specific to the
      etofenprox insecticide were prepared from rabbits and mice, respectively. The
      monoclonal antibodies were more reactive with etofenprox than the polyclonal
      antibodies by C-ELISA. Monoclonal antibody cl 205-65 was found to be the most
      tolerant to methanol, most highly reactive and most specific to etofenprox among
      the antibodies tested.

PMID- 9648232
TI  - Effect of magnetite on the hematocrit value in exsanguinated rats.
AB  - Magnetite prepared by an enzyme-dependent reaction gradually released iron ion
      into the acidic-to-neutral buffer solution. A preparatory experiment was
      performed to examine the efficiency of magnetite as an iron supplement. Feeding
      exsanguinated rats with being magnetite resulted in the hematocrit value being
      recovered without any serious adverse effect on the digestive organs.

PMID- 9648234
TI  - Affinity of antioxidative polyphenols for lipid bilayers evaluated with a
      liposome system.
AB  - We developed a method to measure the amounts of antioxidative polyphenols and
      ubiquinones incorporated into the liquid bilayers of liposomes to estimate their
      affinities for cell membranes. Results were expressed in terms of an "affinity
      factor", calculated by division of the amount of compound incorporated by the
      amount added to the liposomal solution. The results reflected dose-dependence of
      the biological activities of the compound found in earlier in vitro experiments
      with mammalian and bacterial cells.

PMID- 9648235
TI  - Effects of vitamin B6 deficiency on cytokine levels and lymphocytes in mice.
AB  - The effects of vitamin B6 (B6) deficiency on cytokine levels and proportions of
      lymphocyte subsets in BALB/c mice were investigated. The proportion of
      lymphocytes from the thymus and spleen of mice given no B6, that were CD4+ CD8- T
      cells, was larger than in mice given B6, and the ratio of CD8+ to CD4+ T cells in
      the thymus of mice given no B6 was lower. The concentrations of interleukin-5 and
      -10 in spleen cells stimulated in vitro with concanavalin A were significantly
      higher in the mice with B6 deficiency, as was their plasma corticosterone
      concentrations. These results suggested that B6 is necessary to maintain cytokine
      levels and lymphoid function in the thymus and spleen of mice.

PMID- 9648236
TI  - Antimicrobial activity of a compound isolated from an oil-macerated garlic
      extract.
AB  - A compound showing antimicrobial activity was isolated from an oil-macerated
      garlic extract by silica gel column chromatography and preparative TLC. On basis
      of the results of NMR and MS analyses, it was identified as Z-4,5,9-trithiadeca
      1,6-diene-9-oxide (Z-10-devinylajoene; Z-10-DA). Z-10-DA exhibited a broad
      spectrum of antimicrobial activity against such microorganisms as gram-positive
      and gram-negative bacteria and yeasts. The antimicrobial activity of Z-10-DA was
      comparable to that of Z-ajoene, but was superior to that of E-ajoene. Z-10-DA and
      Z-ajoene are different in respect of substitution of the allyl group by the
      methyl group flanking a sulfinyl group. This result suggests that substitution by
      the methyl group would also be effective for the inhibition of microbial growth.

PMID- 9648237
TI  - Molecular cloning and expression patterns of Cu/Zn-superoxide dismutases in
      developing soybean seeds.
AB  - Assuming that the amount of superoxide radicals generated in vivo correlates with
      the production of ergastic substances such as storage proteins, the coordinated
      response of detoxication enzymes such as superoxide dismutases is largely
      exploited to understand the self-defense systems of plant. Here we examined
      expression of the genes for superoxide dismutases during seed development of
      soybean. The cDNAs encoding a cytosolic copper/zinc form and an iron form of the
      above enzyme have been cloned and then employed as probes, separately. Northern
      blotting results suggested that both superoxide dismutase mRNAs are expressed at
      the maximum level, preceding a developmental stage when mRNA encoding glycinin,
      soybean 11S-storage protein, at the maximum.

PMID- 9648238
TI  - Insecticidal and antifungal activities of aminorhodanine derivatives.
AB  - Aminorhodanine (1) showed strong insecticidal activity against Culex pipiens
      pallens and Musca domestica, with respective LD50 values of 0.21 microgram/insect
      and 0.87 microgram/insect. Compound 1 had antifungal activity against Aspergillus
      niger ATCC-16404, Trichophyton mentagrophytes IFO-32412, Candida albicans ATCC
      10231, Hansenula anomala OPS-308 and Penicillium expansum IFO-8800. In
      particular, 1 had potent antifungal activity against Aspergillus niger ATCC
      16404, its minimal inhibitory concentration (MIC) being 6.25 micrograms/ml. Both
      activities of 1 were much higher than those of rhodanine (4), suggesting that the
      introduction of an amino group into N-3 of 4 plays an important role in the
      biological activity of rhodanine-related compounds. On the other hand, N
      acetylaminorhodanine (2) and N-benzoylaminorhodanine (3) did not show either
      activity, suggesting that the free amino group at N-3 of 1 is closely related to
      the inhibitory activity of rhodanine derivatives.

PMID- 9648239
TI  - Thermostable neutral protease resembling thermolysin derived from Bacillus brevis
      MIB001.
AB  - A microbe producing a protease with strong thermostability that was released
      extracellularly was isolated from soil. The isolate, MIB001, grew at from 15 to
      51 degrees C and pH 5.1-8.8 and was tentatively identified as a strain of
      Bacillus brevis. Rabbit antisera raised against a pure preparation of the
      protease did not cross-react with thermolysin or neutral metalloprotease from
      Bacillus stearothermophilus KP1236.

PMID- 9648240
TI  - Interaction between the carboxyl-terminal heparin-binding domain of fibronectin
      and (-)-epigallocatechin gallate.
AB  - We have previously reported that (-)-epigallocatechin gallate (EGCg) inhibited
      lung carcinoma cell adhesion to fibronectin (FN) and demonstrated its interaction
      with FN. In the present work, we studied the interaction between thermolysin
      fragments of FN and EGCg. An amino acid sequence analysis of the fragment bound
      by EGCg-agarose provided its identification as a carboxyl-terminal heparin
      binding domain. Thus, the inhibition of cancer cell adhesion to FN by EGCg is not
      caused by its direct binding to the cell-binding domain containing an Arg-Gly-Asp
      sequence.

PMID- 9648241
TI  - Features of Tri101, the trichothecene 3-O-acetyltransferase gene, related to the
      self-defense mechanism in Fusarium graminearum.
AB  - A structural gene of Tri101, which encodes trichothecene 3-O-acetyltransferase,
      was isolated as a 3-kb XhoI-XbaI fragment from the trichothecene producer
      Fusarium graminearum strain F15. The gene contained no introns, and the coding
      region was 0.7-kb downstream of a putative UTP-ammonia ligase gene which
      obviously is not related to the biosynthesis of trichothecenes. Tri101 was
      expressed when T-2 toxin was added, but this induction was not dependent on the
      expression level of Tri6, a transcription activator gene in the trichothecene
      biosynthetic and regulatory gene cluster.

PMID- 9648242
TI  - cDNA cloning, expression, and characterization of the human bifunctional ATP
      sulfurylase/adenosine 5'-phosphosulfate kinase enzyme.
AB  - A cDNA encoding the human bifunctional ATP sulfurylase/adenosine 5'
      phosphosulfate (APS) kinase was cloned and sequenced. The enzyme contains an APS
      kinase domain in its N-terminal portion and an ATP sulfurylase domain in its C
      terminal portion. Recombinant full-length enzyme and its constituent APS kinase
      and ATP sulfurylase domains were individually expressed, purified, and shown to
      have their respective enzymatic activities.

PMID- 9648243
TI  - Measurement of long-range carbon-carbon coupling constants in a uniformly
      enriched complex polysaccharide.
AB  - A quantitative coherence transfer scheme for 1H-detected measurement of long
      range carbon-carbon coupling constants in NMR spectra of complex carbohydrates is
      described. It is applied to a uniformly highly 13C-enriched monosaccharide and to
      a complex cell wall polysaccharide from Streptococcus mitis J22 having seven
      distinct sugars in the repeating subunit. Coupling values within the ring were
      compared to published values for monosaccharides to demonstrate the validity of
      the method. An attempt was made to relate coupling constants between carbon atoms
      across the glycosidic linkage to the dihedral angles of a recently published
      flexible model for the polysaccharide which is based on 3JCH data. The
      experimental coupling constants do not agree with any single conformation
      demonstrating that the repeating subunit of the polysaccharide must be flexible.
      This conclusion is in accord with results of molecular modeling nuclear
      Overhauser effect and 3JCH data.

PMID- 9648244
TI  - Synthesis of aryl 3'-sulfo-beta-lactosides as fluorogenic and chromogenic
      substrates for ceramide glycanases.
AB  - We have previously reported that 4-methylumbelliferyl 6'-O-benzyl-beta-lactoside
      (2) is a useful substrate for a fluorometric assay of ceramide glycanase (CGase)
      (L.-X. Wang, N. V. Pavlova, S.-C. Li, Y.-T. Li and Y. C. Lee, Glycoconjugate J.,
      13 (1996) 359-365). The introduction of a 6-O-benzyl group at the terminal Gal
      efficiently protected the substrate from its hydrolysis by exo-galactosidase,
      permitting the assay of CGase in crude biological materials. However, a drawback
      of this substrate is its low water-solubility and relatively high Km (at a mM
      level). Introduction of a sulfate group into 4-methylumbelliferyl beta-lactoside
      (1) led to the formation of 4-methylumbelliferyl 3'-O-sulfo-beta-lactoside (3),
      which was found to be a more effective substrate than 2. Moreover, the presence
      of a 3'-O-sulfate group not only increases the water solubility tremendously, but
      also protects the substrate from cleavage by exo-beta-galactosidase as the 6'-O
      benzyl group in 2 does. In addition to the fluorogenic substrate (3), two
      sulfated chromogenic substrates, N-tetradecanoyl-4-O(3'-sulfo-beta-lactosyl)-3
      nitro-L-tyrosine methyl ester (9) and 2-N-(tetradecanoylamino)-4-nitro-phenyl 3'
      sulfo-beta-lactoside (12), were synthesized and their suitability for a
      photometric assay of CGase was evaluated. Substrates 9 and 12, with a long fatty
      acid chain attached to the aglycon part, have a Km value close to that of the
      natural substrate GM1 (at a microM level).

PMID- 9648245
TI  - Synthesis of 1-N-[(2S,4S)- and (2S,4R)-5-amino-4-fluoro-2
      hydroxypentanoyl]dibekacins (study on structure-toxicity relationships).
AB  - (2S,4S)- and (2S,4R)-5-azido-2-O-benzyl-4-fluoro-2-hydroxypentanoic acids (15 and
      19) have been prepared from L-malic acid (1), and coupled to the H2N-1 group of
      3,2',6'-tris(N-benzyloxycarbonyl)-3"-N-(trifluoroacetyl)dibekacin (23), to give,
      after reduction and deblocking, 1-N-[(2S,4S)- and (2S,4R)-5-amino-4-fluoro-2
      hydroxypentanoyl]dibekacins (26 and 27). The fluorinated arbekacin analogs showed
      almost the same antibacterial activities as that of arbekacin, but lower
      toxicity. Comparison of the toxicity between 26 (and 27) and the arbekacin
      analogs (28-30) with change of the 1N-side-chain indicates that the observed
      decrease in toxicity was a function of the chain length rather than the
      introduction of fluorine.

PMID- 9648246
TI  - Synthesis of the unique trisaccharide repeating unit, isolated from
      lipopolysaccharides Rhizobium leguminosarum bv. trifolii 24, and its analogue.
AB  - The synthesis of trisaccharide: 6-d-alpha-L-Talp(1-->2)-alpha-L-Rhap(1-->5)-DHA,
      and its analogue: 6-d-alpha-L-Talp(1-->2)-beta-L-Rhaf(1-->5)DHA is described. In
      the first step a disaccharide, composed of 6-d-L-Talp and L-Rhap was obtained.
      This, in turn, was converted to the corresponding 1-trichloroacetimidate and
      coupled with DHA alcohol to afford the required trisaccharide. Its analogue was
      achieved by the conversion of the above disaccharide to the glycosyl bromide,
      involving the rhamnopyranose ring scission, followed by condensation with DHA in
      Koenigs-Knorr procedure.

PMID- 9648247
TI  - Enzymatic synthesis of N-linked oligosaccharides terminating in multiple sialyl
      Lewis(x) and GalNAc-Lewis(x) determinants: clustered glycosides for studying
      selectin interactions.
AB  - Galactosyltransferase, sialyltransferase, and fucosyltransferase were used to
      create a panel of complex oligosaccharides that possess multiple terminal sialyl
      Le(x) (NeuAc alpha 2-3Gal[Fuc alpha 1-3] beta 1-4GlcNAc) and GalNAc-Le(x)
      (GalNAc[Fuc alpha 1-3]beta 1-4GlcNAc). The enzymatic synthesis of tyrosinamide
      biantennary, triantennary, and tetraantennary N-linked oligosaccharides bearing
      multiple terminal sialyl-Le(x) was accomplished on the 0.5 mumol scale and the
      purified products were characterized by electrospray MS and 1H NMR. Likewise,
      biantennary and triantennary tyrosinamide oligosaccharides bearing multiple
      terminal GalNAc-Le(x) determinants were synthesized and similarly characterized.
      The transfer kinetics of human milk alpha 3/4-fucosyltransferase were compared
      for biantennary oligosaccharide acceptor substrates possessing Gal beta 1
      4GlcNAc, GalNAc beta 1-4GlcNAc, and NeuAc alpha 2-3Gal beta 1-4GlcNAc which
      established NeuAc alpha 2-3Gal beta 1-4GlcNAc as the most efficient acceptor
      substrate. The resulting complex oligosaccharides were chemically tethered
      through the tyrosinamide aglycone to the surface of liposomes containing
      phosphatidylthioethanol, resulting in the generation of glycoliposomes probe
      which will be useful to study relationships between binding affinity and the
      micro- and macro-clustering of selectin ligand.

PMID- 9648248
TI  - Synthesis of the tetrasaccharide repeating unit of the K-antigen from Klebsiella
      type 57.
AB  - Starting from D-galactose and D-mannose two disaccharide blocks, namely 2
      (trimethylsilyl)-ethyl 2,3,4,6-tetra-O-benzyl-alpha-D-mannopyranosyl-(1-->4)-6-O
      (4-methoxybenz yl)- beta-D-galactopyranoside and ethyl 2,3,4,6-tetra-O-benzyl
      alpha-D-mannopyranosyl-(1-->3)-4-O-acetyl- 2,6-di-O-benzoyl-1-thio-beta-D
      galactopyranoside, were synthesized which were then allowed to react, in the
      presence of dimethyl(methylthio)sulfonium triflate to give a tetrasaccharide
      derivative. This compound was converted to 2-(trimethylsilyl)ethyl 2,3,4,6-tetra
      O-benzyl-alpha-D- mannopyranosyl-(1-->3)-4-O-acetyl-2,6-di-O-benzoyl-beta-D
      galactopyranos yl- (1-->3)-[2,3,4,6-tetra-O-benzyl-alpha-D-mannopyranosyl-(1-
      >4)]-tert-but yl (2-O-acetyl-beta-D-galactopyranosid)uronate which, on treatment
      with sodium methoxide followed by hydrogenolysis, afforded the methyl [2
      (trimethylsilyl)ethyl glycosid]uronate of the tetrasaccharide repeating unit of
      the K-antigen from Klebsiella type 57.

PMID- 9648249
TI  - Examination of number-average degree of polymerization and molar-based
      distribution of amylose by fluorescent labeling with 2-aminopyridine.
AB  - Suitable conditions for the fluorescent labeling of the reducing residue of
      amylose with 2-aminopyridine were examined. Amylose of up to 38.5 nmol was
      labeled with a constant labeling efficiency. The same efficiencies were obtained
      for amyloses having a number-average degree of polymerization (dpn) of 521-4400.
      The analysis of labeled amylose on size-exclusion HPLC with refractive index and
      fluorescence detection enabled the determination of dpn and dp distribution on a
      molar basis. The analysis of eight amylose specimens from seven botanical sources
      (potato, sweet potato, barley, wheat, indica rice, japonica rice, and maize) gave
      dpn values in good agreement with those determined by a conventional colorimetric
      method. The molar-based distributions of these amyloses were characteristic of
      botanical source and revealed the presence of several molecular species with
      different dp not detectable in the distribution on a weight basis. Small amyloses
      with a dp less than 10(3) were predominant in the cereals while amyloses with a
      dp over 10(3) were predominant in the tubers, suggesting a difference in the
      biosynthetic process determining the dp distribution of amylose between cereals
      and tubers.

PMID- 9648250
TI  - Regioselective syntheses of sulfated polysaccharides: specific anti-HIV-1
      activity of novel chitin sulfates.
AB  - A novel and convenient method for the regioselective syntheses of sulfated
      analogs of chitin and chitosan is described in relation to studies on structure
      biological activity. Fully protected, soluble derivatives of chitosan were found
      to be useful intermediates for the syntheses of a novel class of sulfated
      polysaccharides, 2-acetamido-2-deoxy-3-O-sulfo-(1-->4)-beta-D-glucopyranan (3
      sulfate, 3S, 4) and (1-->4)-2-deoxy-2-sulfoamido-3-O-sulfo-(1-->4)-beta-D
      glucopyranan (2,3-disulfate, 23-S, 3). These compounds were tested for their
      activities in (i) inhibiting HIV-1 replication in vitro and (ii) inhibiting blood
      coagulation. The results reveal that the selective sulfation at O-2 and/or O-3
      affords potent antiretroviral agents showing a much higher inhibitory effect on
      the infection of AIDS virus in vitro than that by the known 6-O-sulfated
      derivative (6-sulfate, 6S). Moreover, the 23-S product completely inhibited the
      infection of AIDS virus to T lymphocytes at concentrations as low as 0.28
      microgram/mL without significant cytotoxicity. The regioselective introduction of
      sulfate group(s) at O-2 and/or O-3 had little effect on generating anticoagulant
      activity, whereas 6-O-sulfated chitin strongly inhibits blood coagulation. These
      results suggest that the specific interaction of these new types of chitin
      sulfates with gp 120 of the AIDS virus depends significantly on the sites of
      sulfation rather than on the total degree of substitution on sugar residues.

PMID- 9648251
TI  - Structural analysis of oligosaccharide-alditols released by reductive beta
      elimination from oviducal mucins of Rana dalmatina.
AB  - The O-linked oligosaccharides of the jelly coat surrounding the eggs of Rana
      dalmantina were released by alkaline borohydride treatment. Low-molecular-mass,
      monosialyl oligosaccharide-alditols were isolated by anion-exchange
      chromatography and fractionated by consecutive normal-phase high-performance
      liquid chromatography on a silica-based alkylamine column. The structures of the
      oligosaccharide-alditols were determined by 400-MHz 1H-NMR spectroscopy in
      combination with matrix assisted laser desorption ionization-time of flight
      analysis. The five structures were identified range in size from trisaccharides
      to hexasaccharides, possessing a core consisting of Gal(beta 1-3)GalNAc-ol (core
      type 1). Novel oligosaccharide-alditols are: [formula: see text] The carbohydrate
      chains isolated from Rana dalmatina are different from those found in other
      amphibian species, in which the presence of species-specific material has been
      characterized. Since the role of carbohydrates appears more and more apparent
      during the fertilization process, the biodiversity of the O-linked
      oligosaccharides could support such a biological role.

PMID- 9648252
TI  - Biochemical and catalytic properties of an endoxylanase purified from the culture
      filtrate of Thermomyces lanuginosus ATCC 46882.
AB  - An endoxylanase (1,4-beta-D-xylan xylanohydrolase, EC 3.2.1.8) from the culture
      filtrates of T. lanuginosus ATCC 46882 was purified to homogeneity by DEAE
      Sepharose and Bio-Gel P-30 column chromatographies. The purified endoxylanase had
      a specific activity of 888.8 mumol min-1 mg-1 protein and accounted for
      approximately 30% of the total protein secreted by this fungus. The molecular
      mass of native (non-denatured) and denatured endoxylanase were 26.3 and 25.7 kD
      as, respectively. Endoxylanase had a pI of 3.7 and was optimally active between
      pH 6.0-6.5 and at 75 degrees C. The enzyme showed > 50% of its original activity
      between pH 5.5-9.0 and at 85 degrees C. The pH and temperature stability studies
      revealed that this endoxylanase was almost completely stable between pH 5.0-9.0
      and up to 60 degrees C for 5 h and at pH 10.0 up to 55 degrees C for 5 h. Thin
      layer chromatography (TLC) analysis showed that endoxylanase released mainly
      xylose (Xyl) and xylobiose (Xyl2) from beechwood 4-O-methyl-D-glucuronoxylan, O
      acetyl-4-O-methyl-D-glucuronoxylan and rhodymenan (a beta-(1-->3)-beta(1-->4)
      xylan). Also, the enzyme released an acidic xylo-oligosaccharide from 4-O-methyl
      D-glucuronoxylan, and an isomeric xylotetraose and an isomeric xylopentaose from
      rhodymenan. The enzyme hydrolysed [1-3H]-xylo-oligosaccharides in an endofashion,
      but the hydrolysis of [1-3H]-xylotriose appeared to proceed via
      transglycosylation. since the xylobiose was the predominant product. Endoxylanase
      was not active on pNPX and pNPC at 40 and 100 mM for up to 6 h, but showed some
      activity toward pNPX at 100 mM after 20-24 h. The results suggested that the
      endoxylanase from T. lanuginosus belongs to family 11.

PMID- 9648253
TI  - Chemoenzymatic synthesis of carbohydrates.

PMID- 9648254
TI  - Practical synthesis of 4-hydroxy-3-oxobutylphosphonic acid and its evaluation as
      a bio-isosteric substrate of DHAP aldolase.
AB  - An efficient four step synthesis of the title compound 4-hydroxy-3
      oxobutylphosphonate (2) has been developed based on inexpensive 4-ethoxy-1
      hydroxybutane-2-one using an Arbusow reaction (59% overall yield). Several
      dihydroxyacetone-dependent aldolases having different stereospecificities were
      tested for their acceptance of this phosphonomethyl substrate mimic as the aldol
      donor. Individual enzymes belonging to both type I (Schiff base formation) and
      type II (Zn2+ catalysis) mechanistic classes were found to catalyze the
      stereoselective addition of 2 to simple aldehydes to provide bio-isosteric
      analogs of sugar 1-phosphates in high yields. The lack of acceptance by specific
      enzymes is discussed with regard to recent protein X-ray data.

PMID- 9648255
TI  - Diastereoselective resolution of 6-substituted glycosides via enzymatic
      hydrolysis.
AB  - The diastereoselectivity of the enzymatic hydrolyses of 4-nitrophenyl 6-deoxy-6
      methyl-(R)- and (S)-sulfinyl-beta-D-galactopyranoside (1a,b), 4-nitrophenyl 7
      deoxy-D- and L-glycero-beta-D-galacto-heptopyranoside (2a,b) and 4-nitrophenyl
      6,7-anhydro-D- and L-glycero-beta-D-galacto-heptopyranoside (3a,b) was
      investigated using a range of crude glycosidase preparations. It was shown that
      the enzymes display a high degree of discrimination between diastereomers thereby
      demonstrating the utility of glycosidases for the diastereomeric resolution of
      unnatural 6-substituted monosaccharide derivatives.

PMID- 9648256
TI  - Trisaccharide synthesis by glycosyl transfer from p-nitrophenyl beta-D-N
      acetylgalactosaminide on to disaccharide acceptors catalysed by the beta-N
      acetylhexosaminidase from Aspergillus oryzae.
AB  - The beta-N-acetylhexosaminidase from Aspergillus oryzae catalysed the transfer of
      beta-D-N-acetylgalactosaminyl residues from p-nitrophenyl beta-D-N
      acetylglucosaminide on to disaccharide acceptors consisting of thioethyl
      glycosides of alpha-D-Glc-(1-->4)-beta-D-Glc, beta-D-Glc-(1-->4)-beta-D-Glc and
      beta-D-Glc-(1-->6)-beta-D-Glc. The principle of 'anomeric control' was
      exemplified by the results which showed that an alpha-linkage between the units
      of the acceptor favoured exclusively the formation of a new (1-->4)-linkage,
      whereas the beta-configuration in the acceptor led to a mixture of (1-->4)- and
      (1-->3)-linked products, as observed for simple glycosides of monosaccharide
      acceptors. With the thioethyl beta-lactoside as acceptor, beta-D-Gal-(1-->6)-beta
      D-Gal-(1-->4)-beta-D-GlcSEt was formed, owing to the action of residual beta-D
      galactosidase activity in the N-acetylhexosaminidase on the thioethyl beta
      lactoside acting as both donor and acceptor.

PMID- 9648257
TI  - Regioselectivity of the enzymatic transgalactosidation of D- and L-xylose
      catalysed by beta-galactosidases.
AB  - The regioselectivity of enzymatic transgalactosidation depends on the source of
      the beta-galactosidase used. When the galactosyl acceptor only contains secondary
      hydroxyl groups, e.g., D- or L-xylose, it is possible to find an enzyme that
      catalyses preferentially the synthesis of any of the three regioisomers 4-, 3-
      and 2-O-beta-D-galactopyranosyl-D-xylose (1, 2 and 3, respectively) or 4-, 3- and
      2-O-beta-D-galactopyranosyl-L-xylose (4, 5 and 6, respectively). Enriched
      mixtures in 1, 2 or 3 were obtained using beta-galactosidases from Escherichia
      coli, bovine testes or Aspergillus oryzae, respectively, by transgalactosidation
      reaction of O-nitrophenyl-beta-D-galactopyranoside and D-xylose, and enriched
      mixtures in 4, 5 or 6 were obtained in a similar way using beta-galactosidases
      from Aspergillus oryzae, lamb small-intestine (intestinal lactase-phloridzin
      hydrolase) or Saccharomyces fragilis, respectively, using L-xylose as acceptor.

PMID- 9648258
TI  - Enzymatic synthesis, isolation, and analysis of novel alpha- and beta-galactosyl
      cycloisomalto-octaoses.
AB  - Novel branched cycloisomalto-octaoses (CI8s) were enzymatically synthesized by
      transgalactosylation with alpha-galactosidase from coffee bean and beta
      galactosidase preparations from Penicillium multicolor and Bacillus circulans,
      using melibiose and lactose as donor substrates, and CI8 which is a cyclic
      homogeneous oligosaccharide composed of eight glucose units bound by alpha-(1-
      >6)-linkages, as an acceptor. alpha-Galactosyl-CI8s and beta-galactosyl-CI8s
      obtained were isolated and purified by HPLC. Their structures were elucidated by
      matrix-assisted laser desorption ionization time-of-flight mass spectrometry
      (MALDITOFMS) and NMR spectroscopy.

PMID- 9648259
TI  - Chemoenzymatic synthesis of the branched oligosaccharides which correspond to the
      core structures of N-linked sugar chains.
AB  - Synthetic routes are described to a partial structure common to all high mannose
      type sugar chains and complex-type sugar chains based on a chemoenzymatic
      strategy which incorporates, (a) enzymatic synthesis of oligosaccharide blocks
      using glycosidases, and (b) chemical synthesis of the branching oligosaccharides
      via regioselective coupling. All reaction products correspond to key
      intermediates necessary for the construction of N-linked oligosaccharides and we
      have synthesized the branched tetra-manno-oligosaccharide high mannose-type sugar
      chain and the branched hexa-oligosaccharide complex-type sugar chain using this
      simple and direct method.

PMID- 9648260
TI  - Chemoenzymatic synthesis of a novel glycopeptide using a microbial
      endoglycosidase.
AB  - The chemoenzymatic synthesis of a glycopeptide by chemical synthesis of N
      acetylglucosaminyl peptide and enzymatic transfer of an oligosaccharide is
      described. We synthesized glycosylated Peptide T which blocks infection of human
      T cells by human immunodeficiency virus. The first step of the chemoenzymatic
      method is the solid-phase chemical synthesis of N-acetylglucosaminyl Peptide T
      (Ala-Ser-Thr-Thr-Thr-Asn(GlcNAc)-Tyr-Thr) with an N-acetylglucosamine moiety
      bound to the asparaginyl residue by a solid-phase method. This product was
      prepared in high yield by the dimethylphosphinothioic mixed anhydride method
      without protecting the hydroxyl functions of the sugar moiety using Fmoc-N
      acetylglucosaminyl asparagine instead of Fmoc-asparagine. The second step was
      transglycosylation of complex type oligosaccharide to N-acetylglucosaminyl
      Peptide T by a microbial endoglycosidase. The endo-beta-N-acetylglucosaminidase
      of Mucor hiemalis transfer the oligosaccharide of human transferrin glycopeptide
      to N-acetylglucosaminyl Peptide T. The transglycosylation product was confirmed
      to be the glycosylated Peptide T with a sialo biantennary complex type
      oligosaccharide by mass spectrometry. The glycosylated Peptide T was highly
      stable against proteolysis in comparison to native Peptide T and N
      acetylglucosaminyl Peptide T.

PMID- 9648261
TI  - Chemoenzymatic synthesis of a sialylated diantennary N-glycan linked to
      asparagine.
AB  - A partial structure of many glycoproteins, a glycosylated asparagine carrying a
      complex type undecasaccharide N-glycan (Neu5Ac(alpha 2-6)Gal(beta 1-4)GlcNAc(beta
      1-2)Man alpha 1-3) [Neu5Ac(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1
      6)]Man(beta 1-4) GlcNAc(beta 1-4)GlcNAc-Asn) was obtained by total synthesis. As
      a starting material served a chemically synthesized diantennary heptasaccharide
      azide which was deprotected in a three-step sequence in high yield. The reduction
      of the anomeric azide was accomplished with propanedithiol in methanol
      ethyldiisopropylamine. Coupling of the glycosyl amine to an activated aspartic
      acid gave the benzyl protected asparagine conjugate. After removal of the six
      benzyl functions the resulting free heptasaccharide asparagine was elongated
      enzymatically in the oligosaccharide part. The use of beta-1,4
      galactosyltransferase and alpha-2,6-sialytransferase in the presence of alkaline
      phosphatase allowed the efficient transfer of four sugar units to the acceptor
      resulting in a full length N-glycan, a sialyated diantennary undecasaccharide
      asparagine of the complex type.

PMID- 9648262
TI  - Chemoenzymatic synthesis of dendritic sialyl Lewis(x).
AB  - Traditional structure activity relationship studies (SAR) have led to the
      development of numerous sialyl Lewis(x) analogs in the search for potential
      antiinflammatory agents. However, these methods do not take into account cluster
      or multivalent effects. Reported herein is the chemoenzymatic synthesis of di-,
      tetra-, and octa-valent sLe(x) ligands scaffolded on dendrimers. Hypervalent L
      lysine cores with covalently attached 2-acetamido-2-deoxy-D-glucose (N
      acetylglucosamine, GlcNAc) residues were chemically prepared and enzymatically
      transformed into sLe(x) containing dendrimers so that multivalency, and its role
      in selectin-sLe(x) interactions may be evaluated. This work constitutes another
      successful enzymatic synthesis of sLe(x) and represents the first example of
      GlcNAc elongation on a synthetic dendrimer scaffold. These sLe(x) dendrimers are
      currently being investigated as selectin antagonists.

PMID- 9648263
TI  - High performance polymer supports for enzyme-assisted synthesis of
      glycoconjugates.
AB  - Efficient and practical methodology for the construction of carbohydrates,
      including oligosaccharide derivatives and sphingoglycolipids, was established on
      the basis of a water-soluble polymer supports having unique linkers that can be
      cleaved by specific conditions. Novel glycomonomers for the construction of
      polymer supports were synthesized and copolymerized with acrylamide to give three
      types of water-soluble glycopolymers having primer sugars through the specific
      linkers containing (i) p-substituted benzyl group, (ii) L-phenylalanine residue,
      and (iii) ceramide-mimetic L-serine derivative, respectively. These glycopolymers
      were employed for sugar elongation reactions with glycosyl transferases such as
      GlcNAc beta 1,4-galactosyl transferase, beta Gall-->3/4GlcNAc alpha-2,6-sialyl
      transferase, and beta Gall-->3/4GlcNAc alpha-2,3-sialyl transferase in the
      presence of each sugar nucleotide as glycosyl donor to afford polymers having N
      acetyllactosamine, sialyl alpha-(2-->6) N-acetyllactosamine, and sialyl alpha-(2-
      >3) lactose residues in excellent yield. Subsequent hydrogenolysis, hydrolysis
      with alpha-chymotrypsin, or transglycosylation to ceramide with ceramide
      glycanase proceeds smoothly to give N-acetyllactosamine, a versatile sialyl alpha
      (2-->6) N-acetyllactosamine derivative having a terminal amino group, and
      ganglioside GM3 in high yield.

PMID- 9648264
TI  - Enzyme-assisted synthesis of Asn-linked diantennary oligosaccharides occurring on
      glycodelin A.
AB  - The preparation of a series of sialylated and fucosylated N,N'
      diacetyllactosediamine-type diantennary glycopeptides is reported. By sequential
      enzymatic action of jack bean beta-galactosidase, snail beta 4-N-acetyl
      galactosaminyltransferase, bovine colostrum alpha 6-sialyltransferase and human
      milk alpha 3-fucosyltransferase, a diantennary glycopeptide obtained from asialo
      fibrinogen was converted at a 5-mumol scale to a series of structures occurring
      on the glycoprotein glycodelin A, which potentially inhibit human sperm-egg
      binding.

PMID- 9648265
TI  - Acceptor hydroxyl group mapping for calf thymus alpha-(1-->3)
      galactosyltransferase and enzymatic synthesis of alpha-D-Galp-(1-->3)-beta-D-Galp
      (1-->4)-beta D-GlcpNAc analogs.
AB  - The epitope of the acceptor substrate for alpha-(1-->3)-galactosyltransferase
      from calf thymus has been mapped by using a series of mono-deoxygenated and mono
      O-alkylated Type II (beta-D-Ga1p-(1-->4)-beta-D-G1cpNAc) disaccharides. The 4-OH
      group of the beta-D-galactopyranosyl residue is a key polar group essential for
      glycosyl transfer, tolerating neither deoxygenation nor O-alkylation.
      Substitution at positions 6 and 6' by a variety of polar alkyl substituents was
      readily tolerated, allowing the preparative enzymatic synthesis of a series of
      trisaccharide derivatives carrying polar substituents on each of these hydroxyl
      groups. These new analogs are potential inhibitors of Clostridium difficile toxin
      A and of a human anti-alpha-Gal antibody.

PMID- 9648266
TI  - Enzymatic synthesis of site-specifically (alpha 1-3)-fucosylated polylactosamines
      containing either a sialyl Lewis (x), a VIM-2, or a sialylated and internally
      difucosylated sequence.
AB  - By using two different reaction pathways, we generated enzymatically three
      sialylated and site-specifically alpha 1-3-fucosylated polylactosamines. Two of
      these are isomeric hexasaccharides Neu5Ac(alpha 2-3)Gal(beta 1-4)GlcNAc(beta 1
      3)Gal(beta 1-4)[Fuc(alpha 1-3)] GlcNAc and Neu5Ac(alpha 2-3)Gal(beta 1
      4)[Fuc(alpha 1-3)]GlcNAc(beta 1-3)Gal(beta 1-4) GlcNAc, containing epitopes that
      correspond to VIM-2 and sialyl Lewis (x), respectively. The third one,
      nonasaccharide Neu5Ac(alpha 2-3)Gal(beta 1-4)GlcNAc(beta 1-3)Gal(beta 1
      4)[Fuc(alpha 1-3)] GlcNAc(beta 1-3)Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc, is a
      sialylated and internally difucosylated derivative of a trimeric N
      acetyllactosamine. All three oligosaccharides have one fucose-free N
      acetyllactosaminyl unit and can be used as acceptors for recombinant alpha 1-3
      fucosyltransferases in determining the biosynthesis pathways leading to
      polyfucosylated selectin ligands.

PMID- 9648267
TI  - Chemoenzymatic synthesis of a 3IV,6III-disulfated Lewis(x) pentasaccharide, a
      candidate ligand for human L-selectin.
AB  - The disulfated pentasaccharide 3-O-SO3(-)-beta-D-Galp-(1-->4)-[alpha-L-Fucp-(1-
      >3)]-6-O-SO3(-)- beta-D-GlcpNAc-(1-->3)-beta-D-Galp-(1-->4)-D-Glcp was prepared
      according to a chemoenzymatic approach, starting from 4-methoxybenzyl O-(4-O
      acetyl-2,6-di-O-benzyl-beta- D-galactopyranosyl)-(1-->4)-O-2,3,6-tri-O-benzyl
      beta-D-glucopyranoside, obtained in six steps from hepta-O-acetyl lactosyl
      bromide. Coupling of this lactose derivative with O-(3,4,6-tri-O-acetyl-2-deoxy-2
      phthalimido-beta-D-glucopyranosyl) trichloracetimidate afforded, after
      dephthaloylation and re-N-acetylation, 4-methoxybenzyl O-(2-acetamido-2-deoxy
      beta-D- glucopyranosyl)-(1-->3)-O-(2,6-di-O-benzyl-beta-D-galactopyranosyl)-(1--
      >4)- O-2,3,6-tri-O-benzyl-beta-D-glucopyranoside. Regioselective sulfation at the
      primary position of the glucosamine residue was then successfully achieved and
      the benzyl groups were removed. Enzymatic galactosylation of 4-methoxybenzyl O-(2
      acetamido-2-deoxy-6-O-sulfo-beta-D- glucopyranosyl)-(1-->3)-O-beta-D
      galactopyranosyl-(1-->4)-O-beta-D- glucopyranoside sodium salt, and subsequent
      regioselective sulfation at position 3 of the outer galactose residue through the
      stannylene procedure, led then to 4-methoxybenzyl O-(3-sulfo-beta-D-
      galactopyranosyl)-(1-->4)-O-(2-acetamido-2-deoxy-6-sulfo-beta-D- glucopyranosyl)
      (1-->3)-O-beta-D-galactopyranosyl)-(1-->4)-O-beta-D- glucopyranoside disodium
      salt, which was finally fucosylated using human milk alpha-(1-->3/4)
      fucosyltransferase affording, after anomeric deprotection, the target
      pentasaccharide.

PMID- 9648268
TI  - Fucosyltransferase-catalyzed formation of L-galactosylated Lewis structures.
AB  - The Lewis (alpha 1-3/4) fucosyltransferase isolated from human milk could be used
      for preparative fucosylations of the disaccharide acceptors Gal(beta 1
      3)GlcNAc(beta 1-O)R (at position OH-4) and Gal(beta 1-4)GlcNAc(beta 1-O)R (at
      position OH-3) [R = (CH2)8COOMe]. As donors GDP-L-Gal and deoxygenated
      derivatives were used to lead to a series of novel modified trisaccharides of the
      Lewis(a) and the Lewis(x) type, respectively.

PMID- 9648269
TI  - beta-Glucosylation of chitooligomers by galactosyltransferase.
AB  - Galactosyltransferase from bovine milk was found to be able to utilise UDP-Glc to
      transfer Glc onto GlcNAc and chitooligomers[-beta-GlcNAc-(1-->4)-]n, n = 2-4.
      beta-Glucosylated products were used in binding studies with NKR-P1A protein
      cloned from rat natural killer cells.

PMID- 9648270
TI  - Effect of organic cosolvents on the stability and activity of the beta-1,4
      galactosyltransferase from bovine colostrum.
AB  - The influence of various organic cosolvents on the stability and activity of the
      beta-1,4-galactosyltransferase from bovine colostrum (GalT) and of its ancillary
      enzyme UDP-galactose-4'-epimerase has been investigated using the glucosylated
      alkaloid colchicoside (1) as a model substrate. It has been found that some
      cosolvents, such as Me2SO and MeOH, can be used up to 20% v/v without any
      influence on the performance of these enzymes, while others, such as
      tetrahydrofuran, rapidly inactivated GalT at concentrations as low as 5% v/v.
      These results have been exploited for the galactosylation of the poorly water
      soluble coumarinic glucoside fraxin (2).

PMID- 9648271
TI  - The chemoenzymatic synthesis of the core trisaccharide of N-linked
      oligosaccharides using a recombinant beta-mannosyltransferase.
AB  - The chemical synthesis of the beta-mannosyl linkage of N-glycans has presented a
      great challenge to synthetic carbohydrate chemists. We have therefore
      investigated the application of beta-mannosyltransferases to the preparative
      synthesis N-linked core oligosaccharides. In this paper we report the
      chemoenzymatic synthesis of beta-D-mannopyranosyl-(1-->4)-2-acetamido-2-deoxy
      beta-D-glucopyranosyl- (1-->4)-2-acetamido-2-deoxy-alpha-D-glucopyranose on a
      preparative scale using a phytanyl-linked acceptor in the presence of a
      recombinant beta-(1-->4)-mannosyltransferase.

PMID- 9648272
TI  - Structural characterization of the maltose acceptor-products synthesized by
      Leuconostoc mesenteroides NRRL B-1299 dextransucrase.
AB  - The glucooligosaccharides (GOS), produced by Leuconostoc mesenteroides NRRL B
      1299 dextransucrase through an acceptor reaction with maltose and sucrose, were
      purified by reverse phase chromatography. Logarithmic plots of retention time vs.
      dp of the GOS gave three parallel lines suggesting the existence of at least
      three families of homologous molecules. The structure (13C and 1H NMR
      spectroscopy) and reactivity of the purified molecules of the three families were
      investigated. All the products bear a maltose residue at the reducing end. The
      GOS in the first family (named OD) contained additional glucosyl residues all
      alpha-(1-->6) linked. The smallest molecule in this first series was panose or
      alpha-D-glucopyranosyl-(1-->6)-D-maltose (dp 3). All the OD molecules were shown
      to be good acceptors for dextransucrase in the presence of sucrose. The second
      family, named R, was composed of linear GOS containing alpha-(1-->6)-linked
      glucosyl residues and a terminal alpha-(1-->2)-linked residue at the non-reducing
      end of the molecule; the smallest molecule in this family was alpha-D
      glucopyranosyl-(1-->2)-D-panose (dp 4). The third family, R', was formed of GOS
      containing additional residues linked through alpha-(1-->6) linkages that
      constitute the linear chain, and an alpha-(1-->2)-branched residue located on the
      penultimate element of the chain, near the non-reducing end. The smallest
      molecule in this series is alpha-D-glucopyranosyl-(1-->6)-[alpha-D-glucopyranosyl
      (1-->2)]-alpha-D- glucopyranosyl-(1-->6)-D-panose, dp 6. R and R' GOS are very
      poor acceptors for L. mesenteroides NRRL B-1299 dextransucrase. This study makes
      it possible to suggest a rather simple reaction scheme, where molecules Ri, R'i
      and ODi of the same dp all result from the glucosylation of the same GOS: ODi-l.

PMID- 9648273
TI  - Transfer reactions catalyzed by cyclodextrin glucosyltransferase using 4
      thiomaltosyl and C-maltosyl fluorides as artificial donors.
AB  - Cyclodextrin glycosyltransferase enzyme from Bacillus circulans catalyzed the
      effective conversion of 4-thio-alpha-maltosyl fluoride into cyclo-alpha-(1-
      >4(2))-thiomalto -tetraoside, -pentaoside, -hexaoside and linear
      hemithiomaltooligosaccharides. However, under the same conditions, C-maltosyl
      fluoride afforded only linear modified maltotetraose, maltohexaose and
      maltooctaose in moderate yield.

PMID- 9648274
TI  - Synthesis, cytotoxicity and antitumor activity of some new simplified pyrazole
      analogs of the antitumor agent CC-1065. Effect of an hydrophobic group on
      antitumor activity.
AB  - Three simplified pyrazole analogs (7-9) of the antitumor agents CC-1065, were
      synthesized. In in vitro assays, against L1210 cell lines all derivatives showed
      a cytotoxicity in a pM range, values close to the natural target compound (+)-CC
      1065. In in vivo tests, against disseminate L1210 leukemia cells, synthesized
      compounds showed a good potency (O.D. 300 micrograms/Kg) but no activity. These
      observations further validate the effect of the hydrophilic and/or hydrophobic
      characteristics of the substituents present on the molecules, confirming the
      relevance of this phenomena on in vivo activity. In fact in this case the
      increase of hydrophobic characteristics of the molecules produce the loss of
      activity, probably due to a worse bioavailability of the drugs in animals.

PMID- 9648275
TI  - Synthesis, solvolytic stability and cytotoxicity of a modified derivative of
      CPzI, a pyrazole analog of the alkylation subunit of the antitumor agent CC-1065:
      effect of the nitrogen substitution on the functional reactivity.
AB  - The synthesis and the comparative preliminary biological evaluation of a new
      pyrazole analog (16) of the CC-1065 alkylating unit (CPI) are described. This new
      derivative showed low cytotoxicity against L1210 murine leukemia (IC50 3064 nM)
      with respect to reference compound, but contrarily to literature data, was found
      to be more stable to solvolysis than the natural derivative (+/-)-N-Boc-CPI (pH
      3, t1/2 = 212 h vs. 37 h). The results of such investigation showed that
      alkylation of the pyrazole nitrogen caused a loss of cytotoxic activity in vitro
      against tumor cells. This experimental observation allowed us to confirm the
      importance of free N-H for the anticellular activity.

PMID- 9648276
TI  - Mice's brain radioprotection: comparative efficacy of a series of aminothiols and
      aminothiol precursors.
AB  - A serie of radioprotective aminothiols was checked upon irradiation of the mice's
      brain. Cysteamine protects efficiently the brain as soon as 15 minutes after its
      administration. Among the tested aminothiols, it was the most effective compound.
      2-isopropyl 1,3-thiazolane, rapidly hydrolysed, delivers a large amount of
      cysteamine in the brain and was nearly as potent as exogenous cysteamine. The
      other thiazolanes which delivered only progressively cysteamine or 2
      mercaptopropylamine during a long period of time showed lesser efficacy. WR 2721
      which did not penetrate the brain exhibited only a feeble radioprotection. The
      imperviousness to straight active aminothiols may be compensated by the diffusion
      of their precursors across the blood brain barrier and by their speed of
      hydrolysis, yielding active aminothiols during a short period of time between
      their administration and the irradiation.

PMID- 9648277
TI  - Mice's rectum radioprotection: comparative efficacy of a series of aminothiols
      and aminothiol precursors.
AB  - In mice, in a test of rectal gamma irradiation, cysteamine and cysteine are poor
      radioprotectors relative to thiazolanes or WR 2721. Among the tested prodrugs, 2
      isopropyl 1,3-thiazolane was nearly as efficient as WR 2721 as soon as 15 minutes
      after its administration. The guarantee of radioprotection is the effective
      presence of the active aminothiols in the intracellular room during the
      irradiation. In this study, enterocytes of the rectal mucous membrane were not
      sufficiently permeable to exogenous cysteine or cysteamine. The cell
      imperviousness to these straight active aminothiols was compensated by the
      diffusion of their precursors across the membrane.

PMID- 9648278
TI  - Synthesis of some indane derivatives of central muscle relaxant and
      anticonvulsant profiles.
AB  - A series of 2,2-bis(hydroxymethyl)indane derivatives 1a-f, 2a-e and 3a-f were
      synthesized to investigate their central muscle relaxant and anticonvulsant
      activities. The synthesized compounds 1a-f, 2a-e and 3a-f were found to be devoid
      of central muscle relaxant activity using meprobamate (100 mg/kg) as a reference
      standard. However, they showed remarkable anticonvulsant properties in a dose of
      80 mg/kg (s.c.) compared with diphenylhydantoin sodium (80 mg/kg) as a reference
      standard.

PMID- 9648279
TI  - Some 1-substituted 3-aryl-1,4-dihydro-1,2,4-triazino[4,3-a]-benzimidazoles and
      their vasodilatory activities.
AB  - In this study, some 1-substituted 3-aryl-1,4-dihydro-1,2,4-triazino[4,3
      a]benzimidazole derivatives were synthesized, their structures were elucidated,
      and their vasodilatory activities were examined. It was found that the compounds
      under investigation showed appreciable vasodilatory activity.

PMID- 9648280
TI  - N-(2-pyridinyl)-2-[2(3H)-benzazolone-3-yl]acetamides: synthesis, antinociceptive
      and anti-inflammatory activity.
AB  - Eighteen N-(2-Pyridyl)-2-[2(3H)-benzazolone-3-yl]acetamide derivatives have been
      synthesized. The chemical structure of the compounds have been elucidated by
      elemental analysis, IR and 1H NMR spectral data and their antinociceptive and
      anti-inflammatory activities were tested in mice. Compound VII o has shown the
      highest antinociceptive activity, and VII g, j, k, r exhibited relatively high
      antinociceptive activity. In addition, compounds VII d, f, j, p showed
      statistically significant anti-inflammatory activity.

PMID- 9648281
TI  - The newly synthetized pyridobenzoxazocynone inhibits HIV-1 reverse transcriptase
      activity.
AB  - We synthetized pyridobenzoxazocynone that differs in the enlarged eight-membered
      heterocyclic system from the basic structure of pyridobenzoxazepinones a known
      class of non-nucleoside HIV-1 reverse transcriptase inhibitors.
      Pyridobenzoxazocynone hydrochloride was found to inhibit HIV-1 reverse
      transcriptase activity. At concentration 0.35 microM the enzyme activity
      decreased by 64 +/- 14%. Higher concentrations of pyridobenzoxazocynone
      hydrochloride completely abolished the enzyme activity expressed as radioactivity
      of acid insoluble products. These results suggest that pyridobenzoxazocynones may
      represent a new class of HIV-1 reverse transcriptase inhibitors.

PMID- 9648282
TI  - Synergistic effect of microwave heating and hydrogen peroxide on inactivation of
      microorganisms.
AB  - Escherichia coli K-12 isogenous strains and Pseudomonas aeruginosa 102 were used
      to study the synergistic effects of combined microwave heating at short-time
      processing with low concentrations of hydrogen peroxide. The effect of microwave
      heating to temperatures of 40, 50 and 60 degrees C, as well as the concentration
      of hydrogen peroxide (0.05, 0.08 and 0.1%), the sequence of the agents' use, the
      nature of microorganisms on the survival of cells, DNA damages and interaction
      factors were studied. A method of anomalous viscosity time dependencies (AVTD)
      was used for measurement of the changes of genome conformational state (GCS)
      simultaneously with bacterial survival determination. The synergistic effect of
      microwave heating and low concentrations of hydrogen peroxide was observed under
      combined application, and reached a maximum when the cells were exposed to
      microwave heating to 50 degrees C and 0.08% hydrogen peroxide simultaneously.
      Both maxima of cell destruction and DNA injuries have been achieved by successive
      exposure to (MW + 10 min H2O2) to 60 degrees C and 0.08% hydrogen peroxide. The
      mechanisms of synergistic effects, the role of a disturbance of DNA repair and
      the interaction of sublethal injuries caused by different agents are discussed.

PMID- 9648283
TI  - Structure determines function of the retina, a neural center. 2. The second,
      third and fourth circuits.
AB  - Three retinal circuits are analyzed on the bases of established circuit diagrams.
      The synaptic interaction at one circuit involves depolarizing bipolar cells
      connected to rods and shows the important contribution to function of the
      connections between cones and rods including connections of cones to bipolar
      cells connected to rods. Another circuit explains that one type of bipolar cell
      is depolarized at cessation of the stimulus. Because each photoreceptor is
      connected to both on- and off- bipolar cells, on- and off- responses are
      generated from each photoreceptor. The cone connections to rods and to bipolar
      cells connected to rods extend rod vision to low ambient illumination while the
      absence of corresponding connections at cone terminals leads to cone vision being
      blocked at low ambient illumination. The cone connections raise the threshold for
      stimulation of bipolar cells connected to rods and lower temporal resolution of
      rod vision relative to cone vision. The timing of interaction between bipolar
      cells, amacrine cells and ganglion cells in the inner plexiform layer makes
      inhibitory and facilitatory modulation of ganglion cell potential establish
      optimal conditions for ganglion cell activation. The agreement between bipolar
      cell responses determined on the basis of the analysis of the circuit diagrams
      and the responses recorded from bipolar cells shows that the function of a neural
      center such as the retina can be analyzed on the basis of circuit diagrams.

PMID- 9648284
TI  - Cytomegalovirus infection in the submandibular and parotid salivary glands of an
      African grass mouse (Arvicanthus dembeensis).
AB  - The submandibular and parotid glands of one of five specimens of African grass
      mice (Arvicanthus dembeensis) were found to be infected with cytomegaloviruses,
      producing a profound cytomegaly in certain cells at the juncture of secretory
      endpieces and intercalated ducts. These cytomegalic cells tended to have multiple
      nuclei, many of which contained a characteristic reticular inclusion. The viruses
      appeared to arise in association with the intranuclear inclusions, then passed
      through the nuclear envelope to the cytoplasm where they budded into Golgi
      saccules or into small vacuoles, presumably of Golgi origin. Fusion of small
      virus-carrying vacuoles led to the formation of large vacuoles containing a
      plethora of viruses. Viruses were liberated into gland lumina via fusion of the
      vacuoles with the luminal plasmalemma. Fusion of vacuoles with dehiscent ones
      resulted in a form of chain exocytosis. The development of cytomegaloviruses in
      salivary glands may differ in details in a species-specific manner.

PMID- 9648285
TI  - Characterisation of breast stromal fibroblasts: cell surface distribution of
      collagen type IV, laminin and fibronectin.
AB  - A number of cells--fibroblasts, chondrocytes and osteoblasts for example--lack
      the conspicuous cell surface specialisation known as lamina: instead, they
      possess subplasmalemmal linear densities (SLDs). These have been documented
      ultrastructurally as having a lamina-like external component but the extent to
      which they resemble true lamina in terms of protein composition has not been
      investigated. The relationship of the external component of the SLD to true
      lamina was examined in this study by light microscope immunostaining,
      conventional transmission electron microscopy and immuno-electronmicroscopy in
      intralobular stromal fibroblasts. These were studied in normal peri-tumoral
      breast tissue in 17 patients undergoing surgery for breast lesions. For
      ultrastructural immunostaining the indirect immunoperoxidase procedure was used
      on cryostat sections followed by embedding in epoxy resin. To varying degrees,
      collagen type IV, laminin and fibronectin antibodies stained fibroblasts and
      macrophages at the light microscope level. Using immuno-electronmicroscopy, all
      three antibodies localised as foci on fibroblast and macrophage surfaces. These
      occurred with a frequency comparable to that of SLDs as seen in non
      immunostaining ultrathin sections. These observations represent a first attempt
      to define the protein composition of SLDs in fibroblasts in vivo. They provide an
      opportunity of comparing these structures with true lamina and form a basis for
      understanding how fibroblasts interact with their environment.

PMID- 9648286
TI  - Expression of laminin 1 and 2 in brain tumor vessels. An immunohistochemical
      study.
AB  - Components of the blood-brain barrier (BBB) include capillary endothelial cells,
      the vessel basement membrane (BM) and glial cell interface. While endothelial
      cell peculiarities are well known and thoroughly studied, BM morphology and
      functional properties are not. Vessel BM throughout the body is composed of
      laminin 1, the most common variant of laminin, which is made up of alpha 1, beta
      1, and gamma 1 laminin chains, while cerebral vessel BM has been reported to also
      express the alpha 2 chain. In the present study, we show that the BM of newly
      formed vessels in brain tumors presents the same immunohistochemical structure as
      normal brain vessel BM, expressing alpha 1, alpha 2, beta 1, and gamma 1 laminin
      chains. The function of this particular vessel structure in the central nervous
      system is not yet completely understood; however, we hypothesize that vessel BM
      could play a role in impeding the extraneural spreading of brain tumors.

PMID- 9648287
TI  - Angio-tumoral laminin in murine tumors derived from human melanoma cell lines.
      Immunohistochemical and ultrastructural observations.
AB  - Cells in tissues interact with each other and with the extracellular matrix as
      part of a structural and informational unit. During cancer progression, tumor
      cells participate in the formation of a neotissue involving other cells and
      matrix. We recently observed in melanoma an association between tumor and
      endothelial cells via an amorphous matrix containing free laminin. The pericytic
      location of melanoma cells in this angio-tumoral complex raised the question of
      an intramesenchymal migration of metastatic melanoma cells promoted by free
      laminin along the endothelium. However the respective roles of melanoma cells and
      endothelial cells in laminin secretion were not clear. In an attempt to clarify
      the latter issue, we injected into mice three human melanoma cells lines, one
      secreting laminin and two that did not, in order to identify the source of
      laminin secretion in the subsequent interactions between tumor cells and vascular
      endothelium. Using immunohistochemistry and electron microscopy we observed in
      all three cases an amorphous matrix containing laminin between tumor and
      endothelial cells. The fact that two cell lines did not secrete laminin suggests
      that the periendothelial/peritumoral laminin could be of endothelial origin.
      Given the presence of laminin alone during intramesenchymal angiogenesis and
      embryogenesis, we propose an analogous role for endothelial laminin in
      facilitating the migration of melanoma cells along the abluminal surface of the
      endothelium.

PMID- 9648288
TI  - Bone remodeling and macrophage differentiation in osteopetrosis (op) mutant mice
      defective in the production of macrophage colony-stimulating factor.
AB  - Mice homozygous for the osteopetrosis (op) mutation are characterized by
      defective differentiation of osteoclasts, monocytes, and tissue macrophages due
      to a lack of functional macrophage colony-stimulating factor (M-CSF/CSF-1)
      activity. In young (4-6 week-old) op/op mice, the bone marrow cavities were
      filled with spongious bone. In aged (50-72 week-old) op/op mice, the bone marrow
      cavities were markedly reconstructed and marrow hematopoiesis was expanded.
      Numbers of osteoclasts and bone marrow macrophages in aged op/op mice were
      increased but most of the osteoclasts were mononuclear cells and showed poorly
      developed ruffled borders. Lysosomes of bone marrow macrophages were laden with
      abundant crystalloid materials in aged op/op mice and aged littermate mice.
      However, such macrophages were not observed in young op/op mice nor in young
      littermates. In contrast to the marked increase in numbers of osteoclasts and
      macrophages in the bone marrow, the number of Kupffer cells in the liver did not
      increase in aged op/op mice. Kupffer cells in aged op/op mice did not show
      ultrastructural maturation with aging and contained a few crystalloid structures.
      M-CSF administration to aged op/op mice induced numerical increases in Kupffer
      cells and lysosomes in Kupffer cells, disappearance of crystalloid structures in
      lysosomes of Kupffer cells, and the development of ruffled border in osteoclasts.
      These findings indicate that M-CSF-independent mechanisms for macrophage and
      osteoclast development in aged op/op mice are restricted to bone marrow. M-CSF
      plays important roles in the differentiation of macrophage and osteoclast and the
      production and function of lysosomes.

PMID- 9648289
TI  - Quantitative comparison of the morphology of the microvasculature of primary lung
      lesions and metastatic brain tumours.
AB  - Endothelial cells that make up microvessels display a differential expression of
      structure and function that allows them to meet the requirements of the tissues
      they vascularize. The growth of tumours requires neovascularization that occurs
      by angiogenesis, a process by which new capillaries are formed from existing
      vessels. It has been proposed that the local environment determines the
      morphological characteristics of the vessels that vascularize it. The present
      study is a quantitative investigation of the properties of capillaries that may
      contribute to their permeability and their general morphology. Tissue samples
      were taken from primary non-small cell lung carcinomas and from the same tumour
      type that had metastasized to brain. Normal samples were taken from tissue
      distant from the site of pathology. Using transmission electron microscopy,
      profiles of capillaries from the tissue samples were examined and photographed.
      Image-analysis was performed to measure vesicular and mitochondrial density,
      vessel size and vessel wall thickness. The results showed that the morphology of
      the capillaries that vascularize the primary lung tumours differs from the
      morphology of the capillaries that vascularize the metastases of these tumours in
      the brain. In addition to differences in the quantitative observations,
      qualitative differences were observed with respect to the presence of
      fenestrations in the vessel wall, found only in brain tumour vessels, and the
      presence of 'open' junctions, seen only in lung tumour vessels. These results
      suggest that although the environment of the tumour changed the morphology of the
      vessels so they were no longer normal, it did not have the same effect on the
      vessels that vascularize it at the two different sites. Therefore, the response
      of microvessels in the host tissue to factor(s) produced by tumour cells may be
      multifaceted and dependent upon the properties of local vessels.

PMID- 9648290
TI  - Further studies on the phagocytic capacity of chicken thrombocytes.
AB  - Thrombocytes, functional analog to mammalian platelets, have been described as
      the primary circulating phagocyte in chicken blood when challenged with bacteria
      (Chang and Hamilton, 1979). In order to determine if the phagocytic capacity
      could be extended to protozoa, interaction of chicken thrombocytes with
      tachyzoites of Toxoplasma gondii and bloodstream trypomastigotes of Trypanosoma
      cruzi was performed. Interaction with Staphylococcus aureus and Escherichia coli
      was also performed using fluoresceinated and living bacteria, to be examined by
      fluorescence microscopy (after ethidium bromide staining) and transmission
      electron microscopy (after ruthenium red fixation). Using these approaches it was
      possible to distinguish internalized from attached bacteria. T. cruzi was only
      found attached to the thrombocyte surface while T. gondii could be observed
      within the cell. To determine if T. gondii invasion was active or by
      phagocytosis, interaction was performed under conditions where active penetration
      and phagocytosis were inhibited by previous fixation of the parasites or
      treatment of thrombocytes with cytochalasin D, respectively. Interactions with
      fixed T. gondii showed only attached parasites. Cytochalasin D treated
      thrombocytes could still be found with internalized T. gondii. By fluorescence
      and transmission electron microscopy it was possible to observe a small number of
      bacteria internalized by thrombocytes. These findings show that T. gondii invade
      thrombocytes through an active penetration process and these blood cells cannot
      be considered as the primary circulating phagocyte in chicken.

PMID- 9648291
TI  - Investigation of morphological changes in absorptive cells in young adult and
      infant mice fed different amounts of iron for a long-term.
AB  - The changes in fine structure of the intestinal tract in young adult (4 week-old)
      and infant (2 week-old) mice fed a diet containing different amounts of iron salt
      (Fe-0, Fe-2.5, Fe-25: 0, 2.5 and 25 mg Fe/100 g diet, respectively) for a long
      term (1 or 2 weeks) were investigated. The hepatic iron levels in infant mice fed
      Fe-25 for 2 weeks were significantly higher than those observed after 1 week of
      feeding, but there was no such increase in young adult mice during the feeding
      period. Observations of fine structure indicated typical signs of impairment of
      enterocytes due to excess iron such as the opening of intercellular junctions
      between adjacent epithelial cells and the marked appearance of eosinophilic
      leukocytes outside the basement membrane in young adult and infant mice fed Fe
      25. The frequency of the opening in intercellular junctions increased in young
      adult mice fed Fe-25 for 2 weeks, but decreased in infant mice. On the contrary,
      under iron-deficient conditions, the frequency in infant mice was higher than
      that in young adult mice. The appearance of eosinophilic leukocytes indicated
      that some immunological reaction was elicited in both groups of mice fed Fe-25
      for 2 weeks.

PMID- 9648292
TI  - Ultrastructural changes in rat cornea after prolonged hypobaric hypoxia.
AB  - A study was performed to evaluate the effect of prolonged environmental hypobaric
      hypoxia on the ultrastructure of rat cornea. 60-day-old female Wistar rats were
      exposed to a simulated altitude of 5,500 m (350 mmHg) and pO2 of 76 mmHg for 30
      days. Control rats were exposed to atmospheric sea level pressure (760 mmHg) and
      pO2 of 150 mmHg, for the same period. Ultrastructural analysis of the corneal
      epithelium did not reveal any relevant difference between control and treated
      rats. In contrast, the corneal stroma of rats subjected to hypoxia showed
      vascularization with advanced vessel differentiation and signs of active
      proliferation. The endothelium of hypoxic cornea showed swollen mitochondria and
      large empty cytoplasmic areas. The endothelial intercellular junctions could
      hardly be identified in the hypoxic condition. Nevertheless, the most evident
      change in hypoxic cornea was in Descemet's membrane, which was considerably
      thickened, to approximately twice that of the control specimen. These results
      suggest that environmental hypobaric hypoxia induces marked alterations in the
      corneal stroma and endothelium morphology, probably related to reduced oxygen
      tension in the aqueous humor, consequent to hypoxemia.

PMID- 9648293
TI  - Birbeck granules: contribution to the comprehension of intracytoplasmic
      evolution.
AB  - We investigated the ultrastructure of Birbeck granules which are found in some
      malignant histiocytoses such as histiocytosis X, Letterer-Siwe disease, Hand
      Schuller-Christian disease, eosinophilic granuloma of the bone and self-healing
      reticulohistiocytosis. The research is based on the systemic study of Birbeck
      granules, from their formation to intracytoplasmic development, examining with
      the electron microscope at regular intervals ultrathin sections derived from
      biopsies of two cases of Langerhans cell histiocytosis.

PMID- 9648294
TI  - Liver ultrastructural pathology in mice infected with Plasmodium berghei.
AB  - As liver can be an important target organ in malaria, we performed an
      ultrastructural study of hepatic alterations in the final stage of Plasmodium
      berghei infection in mice. Significant hepatocyte abnormalities were found. An
      elevated number of cells showed mitochondria with a high electron-dense matrix
      and multiple changes in shape and size, alterations in the structure of Golgi
      complex, swelling and disorganisation of both rough and smooth-surfaced
      endoplasmic reticulum, differently shaped peroxisome nucleoids, and disappearance
      of glycogen granules. In other areas the hepatocytes were significantly altered
      with diminished microvilli and exhibited myelin-like figures, autophagic
      vacuoles, abundant lipid droplets, and swollen mitochondria in their cytoplasm.
      Necrotic and atrophied hepatocytes with scarce microvilli in the Disse space and
      biliary canaliculi could be seen. Parasitised red blood cells and parasite debris
      were found inside degenerated hepatocytes. Alterations were also noticed in
      microvasculature, including thickened endothelial cells with swollen
      mitochondria, lysosomes and autophagic vacuoles in their cytoplasm. Our results
      demonstrate that hepatocyte damage is an important finding associated with the
      advanced stages of P. berghei malarial infection, which may lead to liver
      dysfunction in this disease.

PMID- 9648295
TI  - Evolutionary sperm morphology and morphometry in armadillos.
AB  - Little is known about the evolution of vertebrate spermatozoa. In most eutherian
      taxa a high degree of uniformity in sperm shapes and dimensions among species was
      observed. The aim of this work is to trace a possible evolutionary change in
      sperm morphology and morphometry in dasypodids. The main difference between the
      spermatozoa of the studied armadillos is the shape of the sperm heads. We have
      classified the spermatozoa into 4 different groups according with their head
      shapes. Sperm from group 1 (Dasypus) are considered ancestral and are clearly
      separated from the others. The remaining sperm types are derivative ones; those
      from group 2 (Tolypeutes) are farther from those of groups 3 (Priodontes and
      Cabassous) and 4 (Chaetopractus, Zaedyus and Euphractus) which would have
      recently differentiated from each other. The sperm shape and size are not
      constant across taxa in armadillos; an important evolutive differentiation was
      established on the sperm morphology and morphometry between the different genera
      in Dasypodidae.

PMID- 9648296
TI  - Pagetic osteoclasts formed in vitro: absence of paracrystalline inclusions.
AB  - In Paget's disease of bone, osteoclasts are increased in number and size and
      contain intracellular paramyxoviral-like inclusions which cross-react with
      antibody against measles, respiratory syncytial, and canine distemper viral
      nucleocapsid antigens. Moreover, measles virus nucleocapsid transcripts are
      present in pagetic osteoclasts and their mononuclear precursors formed in vitro.
      The present study was undertaken to morphologically assess pagetic osteoclasts
      formed in culture; special attention has been directed towards the
      ultrastructural identification of nuclear and cytoplasmic inclusions. Pagetic
      osteoclasts were produced in long-term cultures of non-adherent bone marrow
      mononuclear cells derived from involved bone of patients with Paget's disease.
      These cultured osteoclasts had many of the ultrastructural features of pagetic
      osteoclasts in vivo. Of interest, no viral-like inclusions were observed in
      either the multinucleated osteoclasts or mononuclear cell precursors in these
      cultures. These data suggest that other factors in the bone microenvironment are
      required for viral nucleocapsid formation in pagetic osteoclasts.

PMID- 9648297
TI  - Fighting germs.

PMID- 9648298
TI  - The split brain revisited.

PMID- 9648299
TI  - HIV 1998: the global picture.

PMID- 9648300
TI  - Improving HIV therapy.

PMID- 9648301
TI  - How drug resistance arises.

PMID- 9648302
TI  - Viral-load tests provide valuable answers.

PMID- 9648303
TI  - When children harbor HIV.

PMID- 9648304
TI  - Preventing HIV infection.

PMID- 9648305
TI  - HIV vaccines: prospects and challenges.

PMID- 9648307
TI  - Coping with HIV's ethical dilemmas.

PMID- 9648306
TI  - Avoiding infection after HIV exposure.

PMID- 9648308
TI  - GPs and methadone. Primum non nocere.

PMID- 9648309
TI  - Plagiocephaly--what is the cause?

PMID- 9648310
TI  - Atlas rotation following a blow on the neck.

PMID- 9648311
TI  - Where have the generalists gone?

PMID- 9648313
TI  - Gastroesophageal reflux in adults. Where are we now?
AB  - BACKGROUND: Gastroesophageal reflux is a common form of dyspepsia affecting 20
      40% of the population. OBJECTIVE: Adults experiencing gastroesophageal reflux
      represent a challenging subgroup of patients presenting to primary care
      physicians. Identification of those patients who require medical therapy and
      ultimately surgery, requires an understanding of the mechanisms of disease, the
      available diagnostic tools as well as the array of acid suppressive agents
      currently in use. DISCUSSION: Successful therapy of gastroesophageal reflux may
      reduce complicated oesophageal and extraoesophageal disease.

PMID- 9648312
TI  - Gastroesophageal reflux in children.
AB  - BACKGROUND: Gastroesophageal reflux is common in small children. It is important
      to recognise that its natural history and management differ from reflux in
      adults. OBJECTIVE: This article will summarise the clinical presentation,
      pathophysiology, appropriate investigations and therapy of reflux in small
      children. DISCUSSION: A small amount of regurgitation is common in infancy, and
      is only pathological if it results in harm. In children, reflux-induced injury
      can result from either acid exposure, nutrient loss or respiratory complications.
      Recognised presentations include heartburn, oesophagitis, infant irritability,
      dysphagia, haematemesis, stricture, growth failure, aspiration, apnoea and
      pneumonia. Excessive crying and irritable behaviour in infancy can be due to a
      variety of causes, but there is a fashionable tendency to assume that
      gastroesophageal reflux is a major factor. Regurgitation can be a symptom of
      other conditions such as infection or metabolic disturbance. It is important to
      carefully evaluate any infant with distressed behaviour to exclude a significant
      medical cause. Prolonged oesophageal pH monitoring is a very useful means of
      linking episodes of reflux with putative symptoms. The severity of
      gastroesophageal reflux tends to improve with age in infants and this should be
      considered when advising appropriate therapy, especially fundoplication.

PMID- 9648314
TI  - Classifying hiatus hernia. Does it make a difference to management?
AB  - BACKGROUND: Hiatus hernia is a not uncommon finding but often does not require
      treatment unless symptomatic. At present, hernias are categorised into either the
      sliding variety or the rolling type. Understanding how these differ as to their
      symptoms and their cause provides a basis for a logical treatment plan.
      OBJECTIVE: To describe the differences between a sliding and a rolling hernia,
      highlighting the management approaches for each. DISCUSSION: Sliding hernia is
      often associated with reflux and usually treated medically, but surgery is needed
      for some patients. Para-oesophageal hernia may be a serious problem with major
      complications. Large or symptomatic para-oesophageal hernias need surgical
      treatment.

PMID- 9648315
TI  - Acid pump inhibitors. The treatment of gastroesophageal reflux.
AB  - BACKGROUND: The place of acid pump inhibitors at the top of the efficacy table in
      the league of reflux therapies, and their eager patient acceptance, has aroused
      debate on their role. OBJECTIVE: To understand the role of gastric acid and its
      inhibition in the pathogenesis and treatment of gastroesophageal reflux disease.
      DISCUSSION: Gastroesophageal reflux disease results from excessive exposure of
      the oesophagus to acidic contents. Acid pump inhibitors provide the most
      effective medical control of gastric acid throughout day and night, returning
      oesophageal pH to normal levels. They provide fast symptom relief and rapidly
      restore quality of life in all reflux patients more effectively than H2 receptor
      antagonists or prokinetic drugs. APIs heal oesophagitis of all grades of severity
      and provide safe, effective maintenance of healing with prevention of
      complications in longer term use.

PMID- 9648316
TI  - Meningococcal disease. Is early diagnosis possible?
AB  - Meningococcal disease is a public health problem because of its high mortality
      and is one disease that many GPs have not seen. Case reports illustrate that
      presentation is rarely classic 'meningitis' and further research is required to
      enable earlier detection.

PMID- 9648317
TI  - Questionnaire design and surveys.
AB  - Surveys provide powerful means for systematic collection of information to test
      hypotheses and quantify the extent and nature of phenomena. This article
      discusses survey types and questionnaire design, and outlines 10 steps for
      planning a survey.

PMID- 9648318
TI  - Low back pain in mineral sand mine workers. Incidence and management.
AB  - OBJECTIVES: To establish the prevalence of low back pain suffered by workers in
      three mineral sand mining companies operating in the south west of Western
      Australia; to determine what use was made of health care providers by those
      experiencing low back pain; to derive the perceptions of the value of the
      treatment for low back pain by health care providers. METHOD: A total of 350
      questionnaires were distributed to sand mine workers who were asked to complete
      the questionnaires which were collected 1 week later. RESULTS: completed
      questionnaires were returned by 204 workers giving a 58% response rate. Seventy
      seven percent of male workers and 60% of female workers could remember suffering
      low back pain sometime in their lives. Low back pain was experienced by 61% of
      male sufferers and 57% of female sufferers at least two to three times a month. A
      total of 16% of men and 12% of women experienced low back pain on a daily basis
      while 30% of men and 22% of women reported that the type of work they were doing
      increased their low back pain. Only 19% of all male workers and 6% of all female
      workers had ever taken time off work due to low back pain with the average time
      taken off work for an acute episode, being 14 days. Overall, 47% of respondents
      indicated that the treatment received from general practitioners was ineffective,
      and only 16% of respondents assessed GPs as being better than average.
      Chiropractors were rated higher than physiotherapists or general practitioners in
      providing the most effective treatment for low back pain. Mobilising exercises
      were considered to be better treatment than analgesics or anti-inflammatory
      medication. CONCLUSION: Low back pain is a common problem among mineral sand mine
      workers who preferred the services of the chiropractor or the physiotherapist to
      the general practitioner. Physical treatment modalities with stretching and
      mobilising exercises were preferred to pharmacological treatment.

PMID- 9648319
TI  - Pressure induced pseudodermatitis.

PMID- 9648320
TI  - What has the patient been taking?

PMID- 9648321
TI  - Ankle roll. An approach to assessment.

PMID- 9648322
TI  - Acute fever and skin rash in a young woman.

PMID- 9648323
TI  - Practice tip. Instilling eye drops in children.

PMID- 9648324
TI  - What is folliculitis?

PMID- 9648325
TI  - Selective attention to real phobic and safety stimuli.
AB  - Many previous information processing studies have noted that people with severe
      anxiety selectively attend to threat stimuli. The experiment reported here tests
      the hypothesis that, when real threat stimuli are used instead of semantic
      stimuli, attention may be divided between threat and safety. Spider phobics and
      controls participated in a reaction time experiment, in which the target stimulus
      (a light) was programmed to randomly occur either by the only door to the room or
      by the wall opposite that door. They were asked to press a response button as
      soon as they detected the light coming on by the wall or by the door. Next, for
      half the participants, a live Zebra Tarantula was placed next to the stimulus
      light, either by the door (threat and safety/escape coincide) or by the wall
      (threat and safety/escape divided), and the experiment repeated. The rest of the
      participants repeated the baseline condition to control for practice effects.
      Response latencies to the light stimuli were analysed. Results suggest that
      spider phobics (but not controls) were faster to respond to the light when it
      occurred in the location where the threat and the escape stimuli coincided, (when
      the spider was by the door), than when it occurred in the location where the
      threat and the escape stimuli were divided (when the spider was by the wall).
      These results suggest that phobics may allocate attention not only to threat but
      also to safety. It is proposed that such effects may be less detectable, or
      absent, when the threat stimuli are semantic or symbolic because participants
      discriminate between threat and its symbolic representation.

PMID- 9648326
TI  - The impact of personality disorders on treatment outcome of anxiety disorders:
      best-evidence synthesis.
AB  - Thirty-five studies were traced addressing the impact of comorbid personality
      disorders on treatment outcome of anxiety disorders. The conclusions of this
      review are based on the best-evidence procedure. We used two selection criteria
      that studies had to meet to be included in the present review. The study design
      had to be prospective and a (semi)structured interview had to be used for the
      assessment of personality disorders. From the fifteen selected studies it cannot
      be concluded that, in general, personality disorders affect treatment outcome for
      anxiety disorders negatively. We can only suspect that some personality disorders
      may have an adverse impact upon treatment outcome in anxiety disorders, and they
      should be investigated further. For the time being, in clinical practice one has
      to be cautious in relating personality disorders to less well treatment outcome
      in axis I anxiety disorders.

PMID- 9648327
TI  - A retrospective study of the learning history origins of anxiety sensitivity.
AB  - Anxiety sensitivity (AS; the fear of anxiety-related sensations) has been
      proposed as a risk factor for the development of panic disorder. The present
      study involved a conceptual replication of Ehlers' (1993, Behaviour Research and
      Therapy, 31, 269-278) study on childhood learning experiences and panic attacks,
      but also extended her work by investigating the relationship between early
      learning experiences and the development of AS, in a non-clinical sample. A
      sample of 551 university students participated in a retrospective assessment of
      their childhood and adolescent instrumental and vicarious learning experiences
      with respect to somatic symptoms (i.e. anxiety and cold symptoms, respectively)
      using an expanded version of Ehler's (1993) Learning History Questionnaire. AS
      levels were assessed using the Anxiety Sensitivity Index, and panic history was
      obtained using the Panic Attack Questionnaire, Revised. Contrary to hypotheses,
      the learning experiences of high AS individuals were not found to be specific to
      anxiety symptoms, but involved parental reinforcement of sick-role behavior
      related to somatic symptoms in general. High AS subjects reported both more
      anxiety and cold symptoms prior to age 18 than individuals with lower levels of
      AS. In addition, both cold and anxiety symptoms elicited more special attention
      and/or instructions from parents for high AS individuals to take special care of
      themselves. These findings are contrasted with the results for self-reported
      panickers who reported more learning experiences (modeling and parental
      reinforcement) specific to anxiety-related symptoms, than the non-panickers. The
      results suggest that higher-than-normal levels of AS may arise from learning to
      catastrophize about the occurrence of bodily symptoms in general, rather than
      anxiety-related symptoms in particular.

PMID- 9648328
TI  - Private body consciousness, anxiety and pain symptom reports of chronic pain
      patients.
AB  - An information processing model of pain symptom perception and reporting predicts
      that individuals prone to high levels of attentional self-focus and negative
      affect will report more pain than individuals low in these characteristics. Past
      research on college student and medical patient samples has shown that
      individuals high in private body consciousness (PBC), or attentional self-focus
      and who report higher levels of anxiety report more pain symptoms than
      counterparts low in PBC and anxiety. The present study examined effects of PBC
      and anxiety on pain reports of individuals suffering chronic pain (N = 144). Pain
      patients suffering chronic headache, low back pain, rheumatoid arthritis and
      fibromyalgia were included in the sample. A non-pain control sample (N = 31) was
      also studied to examine potential differences between controls and pain patients.
      Results indicated that pain patients reporting high levels of PBC reported more
      pain, although the effects of anxiety on pain reports among pain patients was not
      significant. Controls did not differ from pain patients on PBC, nor did the 4
      groups of pain patients differ on PBC, suggesting PBC is a dispositional
      variable. Implications for the importance of attentional self-focus in pain
      symptom reporting are discussed.

PMID- 9648329
TI  - Evidence for a non-associative model of the acquisition of a fear of heights.
AB  - Theories that fear results from previous traumatic experience (i.e. conditioning
      theories) have enjoyed widespread support for over half a century. Recent
      research, however, has cast doubt on the validity of these models in some
      specific phobias. Two studies on the etiology of height phobia have obtained
      findings consistent with a non-associative, evolutionary explanation of fear
      acquisition (Menzies and Clarke, 1993a, Behaviour Research and Therapy, 31, 355
      365; Menzies and Clarke, 1995a, Behaviour Research and Therapy, 33, 795-805).
      Unfortunately, the retrospective nature of these studies limits the conclusions
      that can be drawn from these data. Like all retrospective research, these studies
      depend on adult subjects imperfect ability to recall conditioning events that may
      have occurred many years earlier. The present investigation overcomes these
      methodological shortcomings by examining the relationship between putative
      conditioning events before the age of 9 yr and the presence of height fear at
      ages 11 and 18 yr in a large birth cohort studied longitudinally. To our
      knowledge this is the first study that has prospectively examined the
      relationship between relevant traumatic events early in life and the onset of
      height fear in late adolescence. No positive relationship was found between a
      history of falls resulting in injury (i.e. fracture, dislocation, intracranial
      injury or laceration) before the age of 9 and fear of heights at age 11 or 18.
      Interestingly, falls resulting in injury between the ages of 5 and 9 occurred
      more frequently in those without a fear of heights at 18 (P < 0.01)--a finding in
      the opposite direction to that predicted by conditioning theory but consistent
      with non-associative theories of fear acquisition. In general, the results
      provide strong support for non-associative models of fear and are difficult to
      reconcile with conditioning theories.

PMID- 9648330
TI  - A measure of anxiety symptoms among children.
AB  - The Spence Children's Anxiety Scale (SCAS) is a child self-report measure
      designed to evaluate symptoms relating to separation anxiety, social phobia,
      obsessive-compulsive disorder, panic-agoraphobia, generalized anxiety and fears
      of physical injury. The results of confirmatory and exploratory factor analyses
      supported six factors consistent with the hypothesized diagnostic categories.
      There was support also for a model in which the 1st-order factors loaded
      significantly on a single 2nd-order factor of anxiety in general. The internal
      consistency of the total score and subscales was high and 6 month test-retest
      reliability was acceptable. The SCAS correlated strongly with a frequently used
      child self-report measure of anxiety. Comparisons between clinically anxious and
      control children showed significant differences in total SCAS scores, with
      subscale scores reflecting the type of presenting anxiety disorder of the
      clinical samples.

PMID- 9648331
TI  - Thought suppression produces a rebound effect with analogue post-traumatic
      intrusions.
AB  - Attempts to suppress traumatic material may be involved in the development and
      maintenance of post-traumatic stress disorder (PTSD). In order to investigate
      this possibility, analogue post-traumatic intrusions were induced in normal
      participants by means of a distressing film. For comparison, a second film was
      used to induce intrusions about polar bears. It was hypothesized that the
      suppression of these intrusions would produce an immediate decrease but a delayed
      increase ("rebound effect") in their frequency. It was also predicted that the
      rebound effect would be larger for the analogue traumatic intrusions. Each film
      was followed by two consecutive time periods during which participants' thoughts
      were recorded. During the first period, the suppression group was instructed to
      suppress thoughts about the film whilst the control group merely recorded their
      thoughts. During the second period, both groups merely recorded their thoughts.
      The results supported the immediate decrease hypothesis for both types of
      intrusion. As predicted, there was a rebound effect for analogue traumatic
      intrusions although not for polar bear thoughts. Several methodological issues
      relating to the findings are highlighted. The possible implications of a rebound
      effect with trauma-relevant intrusions are discussed with reference to PTSD.

PMID- 9648332
TI  - The effect of attempted thought suppression in acute stress disorder.
AB  - Attempted suppression of traumatic memories was investigated in survivors of
      motor vehicle accidents with acute stress disorder (ASD; n = 24) and without ASD
      (n = 24). Participants monitored their trauma-related thoughts for three 5-minute
      periods. In Period 1, participants were instructed to think about anything. For
      Period 2, participants were administered suppression or non-suppression
      instructions relating to thoughts of the trauma. In Period 3, participants were
      again instructed to think about anything. ASD participants reported higher
      ratings of anxiety, frequency of trauma-related thoughts, and attempted
      suppression of trauma-related thoughts than non-ASD participants. Participants
      who were given suppression instructions demonstrated a delayed increase in trauma
      related thoughts in the period subsequent to suppression.

PMID- 9648333
TI  - Dental fear with and without blood-injection fear: implications for dental health
      and clinical practice.
AB  - The relation between dental, blood and injection fear and oral health was
      examined in 936 New Zealand 18-year-olds. Of the approximately ten percent (n =
      96) of the sample who reported a dental fear, 1 in 10 also reported a fear of
      blood and 53% a co-morbid fear of injections. Study members with dental fear
      alone or co-morbid dental and blood or injection fear had significantly worse
      oral health (i.e. greater caries experience) than a no-fear comparison group or
      individuals with blood-injection fear only. Further, individuals with dental and
      blood or injection fear had a significantly higher level of recent tooth decay
      than individuals with dental fear alone. Time since last dental treatment also
      tended to be highest in this group. Implications for dental health and practice
      were discussed.

PMID- 9648334
TI  - The prospect of predictive testing for personal risk: attitudes and decision
      making.
AB  - As predictive tests for medical problems such as genetic disorders become more
      widely available, it becomes increasingly important to understand the processes
      involved in the decision whether or not to seek testing. This study investigates
      the decision to pursue the possibility of testing. Individuals (one group who had
      already contemplated the possibility of predictive testing and one group who had
      not) were asked to consider predictive testing for several diseases. They rated
      the likelihood of opting for testing and specified the reasons which they
      believed had affected their decision. The ratio of the numbers of reasons stated
      for testing and the numbers of reasons stated against testing was a good
      predictor of the stated likelihood of testing, particularly when the reasons were
      weighted by utility (importance). Those who had previously contemplated testing
      specified more emotional reasons. It is proposed that the decision process is
      internally logical although it may seem illogical to others due to there being
      idiosyncratic premises (or reasons) upon which the decision is based. It is
      concluded that the Utility Theory is a useful basis for describing how people
      make decisions related to predictive testing; modifications of the theory are
      proposed.

PMID- 9648335
TI  - Pain-related anxiety predicts non-specific physical complaints in persons with
      chronic pain.
AB  - Persons with chronic pain often report a range of physical symptoms beyond their
      primary pain complaint itself. We predicted that non-specific physical symptom
      complaints would correlate more strongly with pain-related distress than with
      general measures of distress, and that they would contribute directly to
      disability. Results from 210 adults with chronic pain showed that collateral
      physical complaints are common in persons with chronic pain. Correlational
      analyses showed that greater reporting of physical complaints was associated with
      reports of higher pain severity, higher levels of depression, more cognitive,
      escape/avoidance, fearful appraisal, and physiological symptoms of pain-related
      anxiety and more physical and psychosocial disability. Regression analyses showed
      that, with pain-related anxiety variables entered either before or after
      depression, physiological symptoms of pain-related anxiety significantly
      predicted physical complaints. In comparison with cognitive and somatic
      depression symptoms physiological symptoms of pain-related anxiety were the
      stronger predictor.

PMID- 9648336
TI  - How do I look with my minds eye: perspective taking in social phobic imagery.
AB  - This study explored perspective taking in social phobics' images of past anxiety
      provoking social situations and non-social situations. For images of social
      situations, social phobics were significantly more likely than non-patient
      controls to take an observer perspective, viewing themselves as if from an
      external point of view. In contrast, social phobics and controls did not differ
      in the perspective taken in images of non-social situations, which were generally
      viewed from a field perspective (seeing the situation as if looking out through
      their own eyes). The clinical significance of these findings is briefly
      discussed.

PMID- 9648337
TI  - The long-term outcome of cognitive behaviour therapy for adults in routine
      clinical practice.
AB  - It is recognised that there is a comparative lack of evidence on the long-term
      outcome of cognitive behavioural therapy for patients seen in ordinary clinical
      settings, as opposed to research trials. This paper presents some data on the
      outcome of 36 adult patients followed up an average of nearly two years after the
      end of therapy in a National Health Service CBT clinic. Whilst the vagaries of
      data collection in clinical practice mean that the generalisability of these
      results is still tentative, they suggest that the outcome at the end of treatment
      was generally well-maintained over the follow-up period, with most patients
      maintaining fairly stable scores on the measures used, and the rest roughly
      equally divided between those who deteriorated and those who improved further. A
      high proportion of patients at follow-up reported that they were still using
      various CBT strategies which they had learnt during therapy.

PMID- 9648338
TI  - Weekly assessment of worry: an adaptation of the Penn State Worry Questionnaire
      for monitoring changes during treatment.
AB  - Development and validation of the Penn State Worry Questionnaire. Behaviour
      Research and Therapy, 28, 487-495.] for weekly assessment of worry was evaluated
      in a brief treatment study. Cognitive restructuring techniques were taught to 28
      nonclinical high-worriers, 14 of whom served as a control group in a lagged
      waiting-list design. Results showed that the Penn State Worry Questionnaire-Past
      Week (PSWQ-PW) was highly reliable and substantially valid in the assessment of
      both (a) weekly status of worry and (b) treatment-related changes in worry:
      average Cronbach's alpha was 0.91; average convergent correlation with a past
      week adaptation of the Worry Domains Questionnaire [Tallis, F., Eysenck, M. W.
      and Mathews, A. (1992). A questionnaire for the measurement of nonpathological
      worry. Personality and Individual Differences, 13, 161-168.] was 0.63 and pre
      post improvement on PSWQ-PW showed a 0.71 correlation with the Questionnaire of
      Changes in Experiencing and Behavior [Zielke, M. and Kopf-Mehnert, C. (1978).
      Veranderungsfragebogen des Erlebens und Verhaltens. Weinheim, Germany: Beltz Test
      Gesellschaft.]. It is concluded that the PSWQ-PW is a useful instrument for
      monitoring pathological worry in experimental and applied settings.

PMID- 9648339
TI  - [Cardiac accidents of locoregional anesthesia: experimental study of risk factors
      with bupivacaine].
AB  - Cardiac disorders are observed when excessive plasma concentrations of local
      anaesthetics are reached, following for instance intravascular accidental
      injection for epidural anaesthesia or brachial plexus block. Bupivacaine
      particularly, which is one of the most used local anaesthetics, adversely affects
      intraventricular conduction and cardiac contractile strength from the 3.0-4.0
      micrograms/ml blood levels. Depression of conduction is especially to be feared,
      for it can result in reentrant arrhythmias likely to degenerate into often fatal
      ventricular fibrillation. Such accidents may sometimes occur at far lower
      concentrations, subsequent to diffusion into systemic circulation from the
      injection site (0.4-1.2 micrograms/ml). These accidents were probably due to
      various factors which concomitantly intervene during the anaesthesia. We could
      identify a number of these factors by associating them to an intravenous infusion
      of bupivacaine (0.04 mg/kg/min after a loading dose of 1.00 mg/kg) in animals
      (dogs and pigs) under electrocardiographic monitoring, in which conduction time,
      monophasic action potential duration, effective refractory period and electrical
      fibrillation threshold were determined in the ventricular fibres. The
      electrophysiological changes due to bupivacaine may be enhanced by 1) dilution
      hyponatremia (115-110 mmol/l) induced by a short (5 min) intravenous 10 ml/kg/min
      infusion of hypotonic solution and/or hyperkalemia (7-8 mmol/l) induced by 0.05
      mmol/kg/min infusion of potassium chloride; 2) the acceleration of cardiac
      contractions (180-210 beats/min) induced by ventricular pacing; 3) mild
      hypothermia (35-34 degrees C) induced by blood cooling in an extracorporeal
      circuit; 4) myocardial ischaemia induced by complete temporary occlusion of the
      left anterior descending coronary artery near its origin. The risk of cardiac
      accidents, possibly severe, is therefore enhanced by each of these factors
      capable of lowering the concentration required for their triggering and, of
      course, the combination of two or several of them. On the contrary, the knowledge
      of these factors should allow to prevent most of cardiac accidents of
      locoregional anaesthesia.

PMID- 9648340
TI  - [Reverse cholesterol transport and use of transgenic mice and rabbits to reveal
      candidate genes for protection against atherosclerosis].
AB  - Atherosclerosis is the leading cause of death in industrial societies. In France,
      215 men out of 100,000 aged from 25 to 64 years old suffered of a myocardial
      infarction in 1992 and due to this disease 67 men out of 100,000 died.
      Hypercholesterolemia corresponding to a high LDL cholesterol level is an
      important risk factor of myocardial infarction. Nevertheless a low cholesterol
      level in the HDL fraction (frequently associated with an increase in
      triglycerides concentrations) is a common abnormality found in patients with
      confirmed coronary artery disease. Therefore, besides tentatives to reduce
      triglycerides and LDL cholesterol levels, a therapeutical strategy consists in
      increasing the serum HDL cholesterol concentration in order to improve the
      "reverse cholesterol transport". Apo A-I is the major protein of HDL. Studies in
      mice and rabbits transgenic for human apo A-I showed that overexpression of this
      protein in these animals resulted in an increase in the HDL cholesterol level.
      The serum of these animals contents a high concentration of particles containing
      human apo A-I but not mouse apo A-II (LpA-I) and presents a higher ability to
      induce cellular cholesterol efflux than the serum of the control mice. These
      alterations result in a reduction of atherosclerosis development when these
      animals are submitted to a cholesterol rich diet. Lecithin cholesterol acyl
      transferase (LCAT) is a major enzyme in the metabolic cascade leading to the
      return of cholesterol to the liver. The metabolic role of LCAT is to esterify the
      free cholesterol of native HDL. Native HDL acquire free cholesterol during the
      transfer of cholesterol from the cell membrane to the particle during the
      cellular cholesterol efflux, which is the first step of the "reverse cholesterol
      transport". Mice and rabbits transgenic for human LCAT have higher HDL
      cholesterol levels. Transgenic rabbits but not transgenic mice are protected
      against diet induced atherosclerosis development. Nevertheless, cholesterol fed
      mice which are transgenic for both human LCAT and simian cholesteryl ester
      transfer (CETP) protein do not develop atherosclerosis. This data indicates that
      over production of LCAT reduces atherosclerosis when CETP is naturally (rabbit)
      or artificially (CETP transgenic mice) expressed in the animals. Tentatives of
      gene therapy in mice induced by adenovirus-mediated transfer of human apo A-I and
      LCAT genes also increased circulating apo A-I and LCAT. Therefore apo A-I and
      LCAT are two potential targets for gene therapy in patients with atherosclerosis
      associated with a low HDL cholesterol level.

PMID- 9648341
TI  - [Surgical hysteroscopy in the treatment of septate uterus: systemic treatment or
      selective indications].
AB  - OBJECTIVES: A retrospective study to evaluate the fertility rate after endoscopic
      hysteroplasty in the case of a septate uterus. METHOD: From 1st January 1988-31st
      December 1996, 93 patients showing a septate uterus were treated by endoscopic
      hysteroplasty. The hospitalisation is short: one day surgery or out office. A
      control of uterine cavity by hysteroscopy did next to two months. RESULTS:
      Patients were evaluated after a period in excess of 6 months (6 months-8 years).
      63 pregnancies were achieved amongst the 84 patients to be reviewed (75%). The
      fertility rate achieved is higher amongst infertile patients (80.3%) compared
      with that of sterile patients (64%). CONCLUSION: In the presence of septate
      uterus the endoscopic hysteroplasty is an efficient treatment in the case of
      secondary infertility and of unexplained sterility.

PMID- 9648342
TI  - [Presentation of the Environmental-Health Prize 1997: Lyme borreliosis].
AB  - Lyme borreliosis is an infectious disease, with multisystem involvement, due to a
      spirochete known as Borrelia burgdorferi, transmitted to humans by ticks; its
      recent emergence is, in part, the consequence of reforestation and the rise in
      deer and rodents populations. The prevention and the treatment of this disease
      are well standardized, the main risk being its misdiagnosis.

PMID- 9648343
TI  - [Lyme borreliosis, emergent disease linked with the environment].
AB  - After a short historical presentation of the discovery of the pathogen and its
      vector, the authors present the current data on bacterial and acarologic
      taxonomy. Then they describe their results to assess the mechanisms of
      circulation of the bacteria in the forests of Ile-de-France, particularly in the
      forest of Rambouillet. The combined study of abundance and infection frequency of
      the vectors, small mammals and cervids leads to the characterization of periods
      and areas of higher risk. The risk periods correlate with high density of I.
      ricinus nymphs. The risk areas correspond to those of high density of cervids.
      The role of reservoir of small mammals is confirmed, to the one of large mammals,
      so debated, is clearly demonstrated.

PMID- 9648344
TI  - [Recent aspects of monitoring the dosage of aminoglycosides and vancomycin].
AB  - The narrow range of therapeutic serum concentrations of aminoglycosides and
      vancomycin and the great variations in their pharmacokinetics from one person to
      another makes it important to monitor patients at risk that are treated with
      them. The technique of customizing dosages based on the population
      pharmacokinetics enables an effective treatment to be rapidly established from a
      few measurements of serum concentrations. Aminoglycosides may be given as single
      daily doses because of their concentration-dependent activity. The high peak
      concentration produces an enhanced, prolonged bactericidal activity, while a low
      residual concentration reduces the risk of toxicity. The effect of vancomycin is
      time-dependent. Giving it by continuous i.v. infusion maximizes the time during
      which the serum antibiotic concentration is effective but non-toxic. Monitoring
      serum concentrations can help reduce health care costs. But medical training in
      pharmacokinetics is needed for the optimal use of these therapeutic tools.

PMID- 9648345
TI  - [Membrane receptors and endocrine tumors: expression of vasopressin receptor V1
      modulates the pharmacologic phenotype of adrenocortical tumors].
AB  - A retrospective analysis of 26 adrenocortical tumors responsible for Cushing's
      syndrome showed that vasopressin induced an ACTH-independent cortisol response in
      seven cases (27%). In comparison 68 of 90 patients with Cushing's disease (76%)
      had a positive cortisol response. The mRNA for the V1-type vasopressin receptor
      was detected in normal adrenal cortex and in all tumors, and adenomas had higher
      levels than carcinomas. One adenoma which had a brisk cortisol response in vivo,
      also had in vitro cortisol responses that were inhibited by a specific V1
      antagonist. In situ hybridization showed the presence of V1 mRNA in the normal
      and tumoral adrenal cortex. We conclude that the vasopressin V1 receptor gene is
      expressed in normal and tumoral adrenocortical cells. High--and not ectopic-
      expression occurs in a minority of tumors which become directly responsive to
      vasopressin stimulation.

PMID- 9648346
TI  - [Interactions between central opioidergic and cholecystokininergic systems in
      rats: possible significance for the development of of opioid tolerance].
AB  - Numerous data suggest that cholecystokinin (CCK) acts as an opioid-modulating
      peptide. Because pharmacological and behavioural studies have shown that CCK
      reduces the analgesic effects of opioids, an opioid-mediated activation of CCK
      containing neurones has been proposed to be responsible for the development of
      opioid tolerance. In an attempt to directly assess this hypothesis, we have
      examined, in naive or morphine-tolerant/dependent rats, the possible influence of
      opioid-receptor ligands on--1 the release of CCK from spinal cord slices and--2
      the extracellular levels of CCK in the frontal cortex in awake, freely moving
      animals. Whereas the stimulation of mu or delta 1 receptors inhibited the release
      of the peptide, the stimulation of delta 2 receptors increased CCK release.
      Morphine also increased CCK release, via an action at delta 2 receptors. The
      blockade of delta 1 receptors resulted in an enhancement of the peptide release,
      suggesting that endogenous opioids probably exert inhibitory tonic influence on
      CCK release through the stimulation of delta 1 receptors. In rats rendered
      tolerant/dependent, the inhibitory effects of opioids on CCK release, due to the
      stimulation of mu or delta 1 receptors, and the enhancing effect of delta 1
      receptor blockade, were no longer present. In contrast, the delta 2-mediated
      increase in CCK release persisted. Thus, in morphine-tolerant/dependent rats,
      opioids apparently retain only their excitatory effects on CCK-containing
      neurones. These data support the idea that morphine exerts an excitatory
      influence on central CCKergic neurones, which could tend to reduce the analgesic
      action of the alkaloid, and are in line with the hypothesis that morphine
      tolerance/dependence is associated with an activation of CCK-containing neurones.

PMID- 9648347
TI  - [Transient outward potassium current and repolarization of cardiac cells].
AB  - The transient 4-aminopyridine-sensitive outward potassium current, Ito, is one of
      the ionic membrane currents involved in the repolarization of cardiac action
      potentials. It is present in several species (rat, dog, human) but not in guinea
      pig ventricle. It induces both a marked lowering of the ventricular action
      potential plateau level and an early repolarization wave in the ventricular ECG
      complex of hypothermic rats. In dog ventricle where Ito is much shorter than the
      action potential plateau it can induce only a transient initial repolarization
      (notch). The distribution of Ito is heterogeneous across the dog left ventricular
      free wall, the current being of sizeable amplitude in epicardial and
      midmyocardial layers but absent in the endocardial layer. As a result,
      ventricular action potentials exhibit a notch only in epicardial and mid layers.
      Although the physiological role of Ito remains unclear, we suggest that it can
      participate in the control of calcium current intensity by influencing the level
      of the initial part of the plateau. In pathophysiological conditions, Ito may
      exert unfavourable effects, specially during simulated ischemia when the notch
      reaches the cellular repolarization threshold, thus inducing premature
      termination of the action potential, an obvious cause of drastic electrical
      heterogeneity and resulting severe arrhythmias. The current Ito is reduced in
      moderate cardiac hypertrophy and dilatation and almost entirely suppressed in
      severe hypertrophy. Ito is of larger amplitude in human atrial than in
      ventricular myocytes. The heterogeneous distribution of Ito described in the dog
      has also been found in human ventricles. Because Ito is markedly prolonged at low
      temperatures it is suggested that it can be responsible for the early
      repolarization wave (J wave) observed in the ECG of subjects submitted to
      hypothermia.

PMID- 9648348
TI  - [Use of hematopoietic stem cells from cord blood for allogenic transplantation in
      man].
AB  - Cells contained in umbilical cord blood collected after birth can be
      cryopreserved and used for hematopoietic stem cells transplantation in patients
      with severe hematological disorders. The first success has led to the development
      of cryopreserved umbilical cord blood banks. More than 500 cord blood transplant
      have been reported and more than 10,000 cord blood have been stored for use in
      unrelated and related matched and mismatched transplants. European results show
      that the number of hematopoietic stem cells present in one cord blood is
      sufficient to permanently engraft most of the patients. Graft versus host disease
      is decreased even in unrelated mismatched transplants.

PMID- 9648349
TI  - [Aids and insurance].

PMID- 9648350
TI  - [Xenogenic cellular therapy in man].

PMID- 9648351
TI  - Commentary: making tuberculosis treatment available for all.
AB  - Tuberculosis is one of the major public health problems that WHO has tackled
      throughout the last 50 years. During the pre-clinical era treatment consisted of
      the use of special diets, bed rest in sanatoria, and lung collapse therapy. The
      case fatality rate 5 years after diagnosis was 50% and treatment in a sanatorium
      was expensive and available only to the privileged few. The demonstration in the
      1960s that ambulatory treatment of tuberculosis (one year of isoniazid and p
      aminosalicylic acid) was as effective for patients and their families as
      treatment in a sanatorium heralded the beginning of the end of the sanatorium era
      and the beginning of the era of domiciliary treatment, which could be made widely
      available to many people with the disease in countries where its prevalence was
      high. Subsequent refinements in combination therapy led, in the 1960s, to the
      development of intermittent regimens and, in the 1970s, to short-course regimens
      following the introduction of rifampicin. The currently recommended WHO strategy
      for tuberculosis control is termed DOTS, which is being promoted globally to free
      the world from this millennia-old scourge.

PMID- 9648352
TI  - Research steps in the development and evaluation of public health interventions.
AB  - Presented is a conceptual framework for planning intervention-related research.
      Altogether, nine steps in the process of developing and evaluating public health
      interventions are specified. This process is dynamic and iterative, and all steps
      are not always required, or need follow in sequence. The framework can be used to
      set research priorities by verifying where there is sufficient knowledge to move
      forward and by identifying critical information gaps. It can also help select
      appropriate research designs, as each step is characterized by certain types of
      studies. Greater effort is required to move beyond descriptive epidemiological
      and behavioural studies, to intervention studies. Field trials of public health
      interventions require particular attention as they are often neglected, despite
      their significance for public health policy and practice.

PMID- 9648353
TI  - Priority during a meningitis epidemic: vaccination or treatment?
AB  - From November 1995 to May 1996, a meningitis epidemic occurred in northern
      Nigeria. More than 75,000 cases and 8440 deaths (case fatality rate (CFR), 11%)
      were recorded. Medecins sans Frontieres, in cooperation with the Nigerian
      government, carried out an assistance programme (support to case management,
      surveillance and mass vaccination) in three states (Bauchi, Kano, Katsina) where
      75% of cases occurred. Cost analysis of this assistance in Katsina State reveals
      that case management and mass vaccination were efficient: US$ 35 per case treated
      and US$ 0.64 per vaccination. There was, however, a remarkable difference in cost
      effectiveness between the two strategies. The cost per death averted by improved
      case treatment was estimated to be US$ 396, while the cost per death averted by
      vaccination was estimated to be US$ 6000. In large part this difference is
      attributed to the late start of vaccination: more than 6 weeks after the epidemic
      threshold had been passed. During meningitis epidemics in countries where
      surveillance systems are inadequate, such as in most of sub-Saharan Africa,
      curative programmes should have priority.

PMID- 9648354
TI  - Measuring hunger in the Russian Federation using the Radimer/Cornell hunger
      scale.
AB  - Compared in the study are the results obtained using the Radimer/Cornell hunger
      scale to measure the prevalence of hunger in random samples of mothers and their
      households in the Russian Federation and in the USA in 1993. The 12 items in the
      scale measured hunger at three levels: household, women, and children. If the
      mother answered positively to one of the four items at a particular level, hunger
      was established for that level. The prevalence of hunger in the Russian
      Federation was very high: approximately 77% of the women surveyed, 70% of the
      households, and 32% of the children were classified as hungry. The corresponding
      estimated prevalences of hunger in New York State in 1993 were 46.8%, 25.9% and
      18.3%. In both surveys, children were the least likely to be classified as hungry
      and, if they were, their mothers and households were almost always hungry. In
      both surveys, the hunger scale proved to have criterion-related validity. Basic
      indicators of household socioeconomic and demographic well-being were highly
      related to the three levels of hunger. The higher level of hunger in the Russian
      survey can be explained by the very low incomes. Further study of the nutritional
      status of the Russian population is recommended.

PMID- 9648355
TI  - Prognostic scores for use in African meningococcal epidemics.
AB  - Current WHO guidelines for the case management of meningococcal infections during
      epidemics in developing countries often cannot be applied, largely because of the
      limited health resources in such countries. Several scoring scales based on
      clinical and laboratory features in numerous combinations have been developed for
      the management of meningococcal infections in developed countries, and these have
      facilitated early identification of patients with fulminant disease and thus
      early intervention and reduction in mortality. Unfortunately such scoring scales
      are not appropriate for use in developing countries. We identified hypotension,
      tachycardia, tachypnoea, delay in capillary refill time, coma, absence of neck
      stiffness and petechiae and/or purpura as simple prognostic factors of
      meningococcal disease. Two scores were developed: score I, which includes all
      seven prognostic factors, had a sensitivity and specificity of 80% and 94%,
      respectively. Score II, which excluded hypotension, had a sensitivity and
      specificity of 73.3% and 89.7%, respectively. Quick and simple scoring scales are
      therefore not only applicable but useful for the case management of patients in
      meningococcal epidemics in developing countries.

PMID- 9648356
TI  - Renal dysfunction from cadmium contamination of irrigation water: dose-response
      analysis in a Chinese population.
AB  - In a cadmium-contaminated area in China and a nearby non-contaminated area, 342
      persons were selected for studies of a possible relationship between cadmium dose
      (i.e. total cadmium intake) and response in terms of renal dysfunction. An
      increase in urinary excretion of beta-2-microglobulin (UB2M), adjusted for age
      and sex, was used as an indicator of the response. A statistically significant
      relationship was found between measured cadmium concentrations in whole blood
      (range; < 3.5 to > 15 micrograms/l) and UB2M, and there was a statistically
      significant linear trend. Also, cadmium in urine (< 4 to > 16 micrograms/g
      creatinine) and UB2M displayed a statistically significant positive relationship
      when the total data set was analysed for males and females. The relationship
      between a dose index (obtained from calculated cumulative absorbed doses over a
      lifetime) and UB2M was statistically significant. The results of this first study
      on dose-response relationships in a Chinese population are similar to those
      observed in other populations.

PMID- 9648358
TI  - Bacterial contamination of the lacteal contents of feeding bottles in
      metropolitan Sao Paulo, Brazil.
AB  - Reported are the results of a study in Sao Paulo, Brazil, to evaluate the
      bacterial contamination of the lacteal contents of feeding bottles prepared in
      urban households of low (LSE) and high (HSE) socioeconomic groups, involving 100
      and 32 mothers of infants, respectively. Samples of the lacteal contents of the
      feeding bottles were cultured and the medians (25th and 75th percentiles) of the
      counts (bacteria per ml) were significantly higher in the LSE group: mesophilic
      bacteria, 555,000 (17,250-4,350,000) in the LSE group and 1615 (20-500,000) in
      the HSE group; coliforms, 2400 (19-150,000) in the LSE group and 7 (0-7800) in
      the HSE group. Escherichia coli was isolated from 26% (26/100) of the samples
      from the LSE group and from 6% (2/32) of those from the HSE group (P = 0.03). In
      the HSE group, higher coliform counts were associated with foodhandlers other
      than the mother, lower levels of maternal education, the use of pasteurized milk,
      and the addition of ingredients other than milk. In the LSE group, feeding
      bottles prepared using tap water and those prepared for infants aged over 6
      months had higher coliform counts. In general, the feeding bottles prepared in
      the households studied were heavily contaminated, especially in the LSE group.

PMID- 9648357
TI  - Causes of childhood deaths in Bangladesh: results of a nationwide verbal autopsy
      study.
AB  - While knowledge of causes of deaths is important for health sector planning,
      little is known from conventional sources about the causes of deaths in
      Bangladesh. This is partly due to deficiencies in the registration system and
      partly because few deaths are attended by qualified physicians. The present study
      was undertaken to update the information available on causes of deaths among
      under-5-year-olds, taking advantage of advances in verbal autopsy methodology and
      of the national Bangladesh Demographic and Health Survey conducted in 1993-94.
      About 25% of the deaths were associated with acute lower respiratory infections
      (ALRI) and about 20% with diarrhoea. Neonatal tetanus and measles remained
      important causes of death, and drowning was a major cause for 1-4-year-olds.
      Research and programmes to enable mothers to identify ALRI cases, particularly
      pneumonia, and to encourage timely and appropriate care-seeking and strengthening
      of ALRI case management at the primary care facilities are important priorities.
      While promotion of oral rehydration for watery diarrhoea and antibiotic treatment
      for dysentery should continue, broader preventive interventions including
      provision of safe water and sanitation, and improvements in personal hygiene
      require more attention. Further intensification of immunization programmes and
      innovative experimental interventions to reduce childhood from drowning should be
      designed and tested.

PMID- 9648359
TI  - Estimation of the prevalence and causes of infertility in western Siberia.
AB  - The study examined the epidemiology and causes of infertility in Tomsk, Western
      Siberia, using methodological approaches recommended by WHO and was based on the
      findings for a randomly selected sample of 2000 married women aged 18-45 years.
      Among the respondents, 333 couples were considered infertile since they had not
      conceived after 12 months or more of unprotected intercourse. This group of
      infertile couples was offered comprehensive clinical investigations but only 186
      couples completed them. The infertility rate in Tomsk was 16.7%, being caused by
      diseases of the female reproduction system in 52.7% of the couples and by male
      reproductive diseases in 6.4%. In 38.7% of couples, both spouses suffered from
      infertility, while in 2.2% of cases the cause of infertility was not determined.
      Among the causes of female infertility, secondary infertility dominated (12.9% of
      all the women questioned), while primary infertility affected 3.8% of the women.
      The most frequent causes of female infertility were disturbances to tubal patency
      (36.5%) and pelvic adhesions (23.6%). Endocrine pathology was found in 32.8% of
      cases. The most frequent cause of male infertility was inflammatory disease of
      male accessory glands (12.9%). In 8.6% of cases infection resulted in obstructive
      azoospermia. Varicocele was registered in 11.3% of cases, and idiopathic
      pathospermia in 20.9%. Inflammatory complications among females were 4.2 times
      more frequent than among males.

PMID- 9648360
TI  - Approaches to control sexually transmitted diseases in Haiti, 1992-95.
AB  - Despite major obstacles, activities to control sexually transmitted diseases
      (STDs) were initiated in Haiti in 1992 in collaboration with local
      nongovernmental organizations. The approaches included review of available local
      data, assessment of STD case management practices and constraints, and
      development of specific STD control activities at the primary health care level,
      such as systematic screening of all pregnant women for syphilis and improved
      comprehensive syndrome-based STD case management. The activities included conduct
      of local studies, presentation and dissemination of results to key audiences,
      training of health care providers, improvement of local capacities, and consensus
      building on implementation of STD control approaches. STD awareness and case
      management improved considerably; for example, 69% of the clinicians interviewed
      reported correct STD treatments in the north-eastern primary health care centres
      in 1995, compared with < 10% in 1992. At the end of the project, national STD
      case management guidelines were developed by consensus between the various
      organizations and the Ministry of Health. Lessons learned included the importance
      of local data generation and of communication and collaboration with various
      institutions for consensus-building, the need for continued training, and field
      supervision to ensure behaviour change among STD care providers. A national STD
      control programme should be implemented as soon as possible in both the public
      and private sector. External funding will remain critical to control this
      important public health problem in Haiti.

PMID- 9648361
TI  - [What determines the choice of health care treatment in the town of Contonou
      (Benin)?].
AB  - Households in Contonou show a clear preference for modern medicine. Self
      medication is the first choice, followed by use of private practices, which are
      growing in importance in Benin as treatment options. This preference for private
      medicine seems to meet a demand that is not covered by the public services, which
      occupy the third place among treatment options. The hospital and the practitioner
      of traditional medicine are the last resort where the other choices have not
      produced the expected outcome. The choice of self-medication is determined by the
      patient's assessment that the illness is not serious, by the habit of using a
      certain treatment in response to a familiar symptomatology, and by the desire to
      avoid the expense of a consultation. The recourse to other options is connected
      with the geographical accessibility of the places of consultation, the cost of
      care and treatment, the reception accorded to patients at the place of
      consultation, the seriousness of the illness and, to a lesser degree, the
      relations of kinship with the health personnel in the services visited. The
      choice between the available health services lies principally between private
      clinics and public health centres. There is therefore a need to consider the
      operation of public health centres and the quality of the care they provide since
      this would enable those responsible for health service organization and planning
      to make better informed choices. At the same time, the state should encourage its
      research bodies to study the operation of the private sector in the light of the
      importance of this type of care in the treatment chosen by households.

PMID- 9648364
TI  - Legionnaires' disease in Europe, 1996.

PMID- 9648362
TI  - Haemoculture as a tool for diagnosing visceral leishmaniasis in HIV-negative and
      HIV-positive patients: interest for parasite identification.
AB  - Between May 1993 and June 1996, 65 adults infected with human immunodeficiency
      virus (HIV) and 30 HIV-negative patients (8 children and 22 adults) from the
      Mediterranean region with symptoms that included at least fever were examined for
      Leishmania. A total of 128 bone marrow and 128 peripheral venous blood samples
      were taken and cultured on NNN medium. At the initial diagnosis, 14 (6 HIV
      positive and 8 HIV-negative) of 15 patients with a positive blood culture also
      had a positive bone marrow culture. Two patients (1 HIV-positive and the other
      HIV-negative) had a positive bone marrow culture but a negative blood culture.
      During post-therapeutic check-ups, 7 out of 8 patients with a positive blood
      culture (6 HIV-positive and 1 HIV-negative) also had a positive bone marrow
      culture. On the other hand, three patients (2 HIV-positive and 1 HIV-negative)
      had a positive bone marrow but a negative blood culture. Relapses were more
      frequent (9/65 vs. 3/30) and the demonstration of Leishmania in the blood was
      commoner (6/65 vs. 2/30) in the HIV-positive than the HIV-negative patients.
      Stocks were identified by their isoenzymes: MON-1 from four HIV-positive and
      eight HIV-negative patients, MON-28 from one HIV-positive patient and MON-29 from
      another. For each patient, the same zymodeme was found in bone marrow and blood
      cultures, both at initial diagnosis and at follow-up.

PMID- 9648363
TI  - Selected gastrointestinal pathologies in tropical sub-Saharan Africa.
AB  - Doctors need to be well informed about differences in the presentation of certain
      diseases in tropical and temperate climates. In this article the characteristics
      of some gastrointestinal diseases, as they recur in sub-Saharan Africa, are
      briefly reviewed. Diseases of the stomach--including ulcertaion and cancer--are
      uncommon in Africa, although duodenal ulcer is common all over the tropics. In
      contrast, colorectal cancer is an extremely rare illness in sub-Saharan Africa,
      while hepatocellular carcinoma is much commoner than in Europe or North America
      and the very high incidence of this tumour in tropical countries is cause for
      concern.

PMID- 9648365
TI  - Arboviruses in the Australian region, 1990 to 1998.
AB  - Arboviruses continue to be major human pathogens in the Australian region. This
      report provides a summary of the activities of these viruses over the past eight
      years, and comments on new findings relevant to their respective ecologies. Of
      particular interest and concern is the propensity of these viruses to spread. The
      examples discussed include the initiation of dengue epidemics in north Queensland
      by virus imported in viraemic travellers; the spread of Japanese encephalitis
      virus to the Australasian region and its probable enzootic establishment in the
      south-west of Papua New Guinea; the potential spread of Ross River virus to other
      countries, as demonstrated by the 1979-80 outbreak in the South Pacific, and the
      recent occurrence in military personnel from the United States of America after
      an exercise; and the recent spread of Barmah Forest virus into Western Australia.

PMID- 9648366
TI  - Ross River virus infection in the north-west outskirts of the Sydney basin.
AB  - In early 1997, 69 cases of Ross River virus infection were reported in the north
      western outskirts of Sydney. This represents a substantial increase over the
      maximum of 12 cases reported in any one year since 1991. The majority of cases
      (71%) are thought to have been locally acquired. This is the first reported
      outbreak of Ross River virus infection in this area and highlights the need for
      metropolitan health services to be vigilant about a disease that has primarily
      been associated with rural and semirural areas in New South Wales.

PMID- 9648367
TI  - A presumptive case of fatal Murray Valley encephalitis acquired in Alice Springs.
AB  - A presumptive case of Murray Valley Encephalitis (MVE) acquired in Alice Springs
      in March 1997 is reported. The patient subsequently died in Mackay. The diagnosis
      of Murray Valley Encephalitis was supported by the detection of flavivirus IgM in
      cerebrospinal fluid. Low titres of IgM specific to Murray Valley Encephalitis and
      Alfuy were detected in a single serum sample. The patient's travel movements
      indicate that his infection was acquired in the Alice Springs vicinity. This
      conclusion was further supported by the detection of Murray Valley Encephalitis
      activity in sentinel animals in the area and by the presence of large numbers of
      the principal mosquito vector of Murray Valley Encephalitis in the Northern
      Territory.

PMID- 9648368
TI  - Dengue or Kokobera? A case report from the top end of the Northern Territory.
AB  - In early April 1998, the Centre for Disease Control in Darwin was notified of a
      possible case of dengue which appeared to have been acquired in the Northern
      Territory. Because dengue is not endemic to the Northern Territory, locally
      acquired infection has significant public health implications, particularly for
      vector identification and control to limit the spread of infection. Dengue IgM
      serology was positive on two occasions, but the illness was eventually
      presumptively identified as Kokobera infection. This case illustrates the
      complexity of interpreting flavivirus serology. Determining the cause of
      infection requires consideration of the clinical illness, the incubation period,
      the laboratory results and vector presence. Waiting for confirmation of results,
      before the institution of the public health measures necessary for a true case of
      dengue, was ultimately justified in this case. This is a valid approach in the
      Northern Territory, but may not be applicable to areas of Australia with
      established vectors for dengue.

PMID- 9648369
TI  - Three cases of dengue 1 virus infection from islands in the Gulf of Thailand.
AB  - Three Australian tourists who recently travelled to islands in the Gulf of
      Thailand developed febrile illnesses associated with myalgias, thrombocytopenia,
      and atypical lymphocytosis. Dengue 1 virus was isolated from all three patients.
      The patients' clinical features and serological and virological investigations
      are presented. These cases highlight the need for awareness of dengue amongst
      travellers and the preventive precautions required when visiting endemic regions.
      After the urgent exclusion of malaria, dengue should be considered in the
      differential diagnosis of febrile persons who have recently returned from endemic
      regions.

PMID- 9648370
TI  - Dengue 3 in Cairns: the story so far.

PMID- 9648371
TI  - A case of infant botulism in South Australia.

PMID- 9648372
TI  - National immunisation coverage--interpreting the first three quarterly reports
      from the ACIR.

PMID- 9648373
TI  - Hepatitis A--the neglected sexually transmissible disease.

PMID- 9648374
TI  - Communicable diseases surveillance.

PMID- 9648375
TI  - [Pregnancy outcome after in vitro fertilization].

PMID- 9648376
TI  - [Estrogen-progestin contraception and cardiovascular diseases: the end of
      polemics on the third generation].

PMID- 9648377
TI  - [Perimenopause: limits and pitfalls of colposcopic evaluation].

PMID- 9648378
TI  - [Management of late induced abortions in France].
AB  - In France, the painful ignored question about the taking into charge of
      termination of pregnancy demands requires a careful examination for appraising
      the situation realistically as much as for considering humanly acceptable
      answers. About 6000 women cope every year with this dramatic problem which is
      often medically settled in Holland, Great-Britain and Spain. As it is a question
      of serious psychological circumstances after 20 years dealing with abortion
      medicalization, a status quo, deplored by most of family planning professionals,
      cannot be accepted. A regional health service dealign with late abortions, once
      or twice a week, would be sufficient to resolve most of the problems. Knowing in
      other respects that two thirds of termination of pregnancy demands do not take
      more than 15 weeks of amenorrhoea.

PMID- 9648379
TI  - [Delayed deliveries in multiple pregnancies: is this reasonable?].
AB  - Delivery of viable fetus with a long interval delay is an unusual occurrence.
      There is no clear attitude among obstetricians for such cases. We report a case
      of retention of the second and the third triplet after the delivery of the first
      one at 24 weeks of amenorrhea and 3 days. The duration of the retention was 6
      days. Only the third infant survived. We attempt to outline the difficulties in
      managing such pregnancies.

PMID- 9648380
TI  - [Breech presentation: management (304 cases)].
AB  - BUT: Try to precise the optimal management in 1997 face a breech presentation.
      METHOD: Between January 1991 and December 1995, 304 cases of breech presentations
      were listed at the maternity of Pavillon Victor Olivier (Lille). From these 304
      breech presentations, all parities blended, the authors have analysed the mode of
      delivery of these patients, distinguishing the para one from the multiparous
      women and the preterm babies from the other babies. From this study and a review
      of the literature, were discussed the criterions which can help the practitioner
      to determine the mode of delivery of these fetus. RESULTS: The results show a
      cesarean section (cs) rate of 51% (41% of first intention cs and 10% of second
      intention cs were realized only for primiparity + breech presentation and 67% of
      the para one women benefited from a first intention cs 8.72% of vaginal
      deliveries were complicated, and 5 fetal injuries were noted without sequel. On
      296 live new-borns, only 2 cases of fetal death were perhaps due to the vaginal
      delivery. Fetal mortality is principally reliable at the prematurity and the
      congenital malformations, but finally, not due to mode of delivery. CONCLUSION:
      The difficulty is to determine rigorous criterions of selection to authorize a
      vaginal delivery without spoil the fetal pronostic. The major criterions are a
      perfect radiopelvimetry, an estimated fetal weight < 3800 g for the para one
      women and < 4300 g for the multiparous woman, a well flexed fetal head, favorable
      obstetric conditions ond the absence of maternal or fetal complications. The
      primiparity is not an indication of systematic cesariean section.

PMID- 9648381
TI  - [Influence of weight and distribution of adipose tissue in functional
      hyperandrogenism].
AB  - Approximately half the women with the polycystic ovary syndrome (PCOS) are obese
      or overweight. Obesity and body fat distribution have independent roles in the
      development of hyperandrogenism in PCOS. Most obese and normal weight PCOS are
      insulin resistant and hyperinsulinemic. Moreover, a significant positive
      correlation exists between the degree of hyperandrogenism and that of
      hyperinsulinism. The pathogenetic role of obesity may involve different
      mechanisms, the major one being the hyperinsulemic state, since insulin is
      capable of stimulating ovarian androgen secretion and controlling androgen
      metabolism and transport in peripheral tissues. Abdominal body fat distribution
      in obese women with PCOS amplifies the degree of hyperandrogenism and related
      clinical symptoms and signs. Both loss of body weight and/or the reduction of the
      degree of hyperinsuliemia, induced by diet or insulin-sensitizing drugs, have
      important effects, since they reduce blood androgen levels and can improve
      ovulation and clinical signs of hyperandrogenism.

PMID- 9648382
TI  - [Comparison of laparoscopic and laparotomy colposuspension in the treatment of
      urinary stress incontinence. Comparative study of 72 matched cases].
AB  - The aim of this study was to compare the results of open retropubic (OC) and
      laparoscopic (LC) colposuspension to the Cooper's ligament (Burch operation). We
      matched retrospectively 72 LC and OC according to their ages, the type of
      associated operations and the clinical stages of their urinary incontinence. We
      excluded associated prolapsus, previous surgical procedure for urinary
      incontinence, maximal urethral closure pressure lower than 30 cms of water and
      instability of the detrusor. We estimated the comparability of our two series
      about the other criteria which have an effect upon the post operative results in
      literature. The mean follow up was 17 months for LC and 46 months for OC. LC
      operative time was longer than (Mean: LC: 89 minutes, OC: 42 minutes), women
      considered LC less aching than OC. They needed less postoperative analgesia,
      mostly given only just the day of the procedure. LC length of hospitalization and
      return to normal activity was shorter than OC (Mean: LC: 3 days--OC: 6, 7 days;
      LC: 15 days--OC: 21 days). The graphs of the subjective cure and improvement
      rates made according to the Kaplan-Meier method could be compared with the log
      rank test. (Cure after one year: LC 79%, OC 69%--Improvement after one year: LC
      85%, OC 82%--Cure after two years: LC 68%--OC 64%--Improvement after two years:
      LC 80%--OC 75%).

PMID- 9648383
TI  - [Influence of sexual steroids on behavior in the postmenopause].

PMID- 9648384
TI  - [Treatment of pelvic pain in gynecology].

PMID- 9648385
TI  - [Pain therapy in palliative medicine].
AB  - The large majority of patients being managed in palliative medicine are suffering
      from incurable, far advanced and progressive cancer. An overall treatment
      strategy not only includes the treatment of physical symptoms but also integrates
      the psychological, social and spiritual problems of the patients and his/her
      relatives. The most stressful physical symptom is pain, which may be so severe as
      to be intolerable. With the judicious use of opioids and adjuvant substances,
      this can be managed satisfactorily. The opioid of choice is oral morphine. The
      value of oral oxycodone and hydromorphone has not yet been fully established, and
      it remains to be seen what role they will play in the future. These two
      substances are expected to become available in Germany in 1998.

PMID- 9648386
TI  - [Pain therapy in pediatric oncology].
AB  - Malignancy-related pain is of similar frequency in children and adolescents as in
      adults. In children too evaluation of pain intensity, character and location is
      the basis for individually adapted pain therapy. The choice of medication is
      determined by the pathophysiological cause and the intensity of the pain. In
      addition to non-opioid analgesics, tramadol is used for moderate, and morphine
      for severe, pain. In the case of neuropathic pain, coanalgesics are employed. If
      oral treatment with morphine is no longer possible, pain pumps for continuous
      parenteral treatment must be used in children too. Provided the appropriate
      medical care is possible, parenteral treatment with potent opioids can also be
      applied at home. In children, every effort must be made to make painful
      diagnostic and therapeutic measures as painfree as possible.

PMID- 9648387
TI  - [Phytotherapy. 3: Use in diseases of the respiratory tract].

PMID- 9648388
TI  - [How "ethics arguments" hinder research. With Buxus sempervirens against AIDS?].

PMID- 9648389
TI  - [New therapeutic possibilities in pulmonary emphysema. Conservative therapy-
      surgical lung volume reduction--lung transplantation].
AB  - The spectrum of therapeutic possibilities in pulmonary emphysema has recently
      been expanded by surgical lung volume reduction. Improvements in surgical
      technique have now lowered the mortality rate of the procedure to less than 5%,
      thus providing a chance of prolonging survival and improving the quality of life
      of severely ill patients in need of oxygen. To date, experience has been gained
      with this procedure in several thousands of patients in the U.S.A. and Europe,
      some groups of patients have now been followed up for about three years. The
      procedure is not recommended for use in patients with genetically determined
      alpha 1-antitrypsin deficiency. Surgical bullectomy is practiced when individual
      bullae affect more than 50% of a lung. In special cases, the possibility of lung
      transplantation should also be considered. In addition to the invasive
      approaches, survival, but in particular quality of life, can also be improved by
      conservative procedures. These include medical anti-obstructive treatment, the
      early use of antibiotics in the case of infections, but also physiotherapeutic
      measures such as pursed-lip breathing and exercises to strengthen diaphragma.
      Palliative measures in advanced stages are long-term oxygen therapy and in
      special cases non-invasive self-ventilation.

PMID- 9648390
TI  - [Smoking cessation in unavoidable. Interview by Dr. rer. nat. Renate Leinmuller].

PMID- 9648391
TI  - [Phytotherapy. 2: Use in cardiovascular diseases (and dementia)].

PMID- 9648392
TI  - [Hypertension: pro and contra fixed combination therapy. Pro].

PMID- 9648393
TI  - [Hypertension: pro and contra fixed combination therapy. Contra].

PMID- 9648394
TI  - [Guide for general practice. Much evidence favors broad use of fixed
      combinations].

PMID- 9648395
TI  - [Alpha-1 blockers for therapy of essential hypertension. 2 clinical studies with
      bunazosin].

PMID- 9648396
TI  - [Understanding and properly treating Lyme borreliosis. Family physician study in
      the USA reveals large management deficits].

PMID- 9648397
TI  - [Gonarthrosis--current aspects of therapy with glucosamine sulfate (dona200-S)].
AB  - For many years glucosamine sulfate has been successfully used in the therapy of
      osteoarthritis. Today's importance of the treatment with glucosamine sulfate is
      even increasing. Glucosamine sulfate meets all standards of an efficient and well
      tolerated drug. This is proven by experimental as well as clinical studies, in
      which glucosamine sulfate was tested in accordance with the current state of
      scientific research. The results show that glucosamine sulfate will lead to long
      lasting pain reduction and functional improvement by means of increasing
      anabolical mechanisms, reducing the activity of proteolytic enzymes and by its
      antiinflammatory effect. Since this therapeutical effect is not due to an
      inhibition of the prostaglandin synthesis, treatment is not accompanied by the
      known unwanted side effects. Glucosamine sulfate is very well tolerated by
      patients of all ages under short-term as well as long-term treatment.

PMID- 9648398
TI  - [Localization of the gene for 4 hereditary multiple exostoses families].
AB  - We investigated 11 families with hereditary multiple exostoses (EXT) by linkage
      analysis using 8 short-tandem-repeat (CA)n polymorphic markers on chromosomes 8,
      11 and 19. The Lod score in four families indicated that the gene responsible for
      EXT is located in the pericentromeric region of chromosome 11.

PMID- 9648399
TI  - [The genetic analysis of amplitude of progesterone secretion in serial blood
      collection from tail in min sows].
AB  - 28 adult Min sows (3-7 parities), represented 9 sire families were selected to
      conduct the continual blood collection from the tail for two hours at the
      interval of ten minutes between 9:00-11:00 in the morning on the sixth day after
      the last mating. The content of progesterone was assayed by radio-immunological
      assay. The amplitudes of the secretion of progesterone were generated by the
      procedure of HORM fft. exe complied by the author. It is difficult to get a
      reasonable conclusion from the content analysis, because the content varied
      widely between different points of blood collection in single sow. After Fourier
      conversion, the heritability of amplitude for the fifth partial wave was high (h2
      = 0.932); middle for the basal, 2nd and 3rd partial waves; lower for others. This
      supported the idea that prolific sows had more active secretion of progesterone
      in luteal cells. The coexist of low and high heritability components in amplitude
      of progesterone secretion showed that the activities of progesterone secretion
      were influenced by both the genetics and environments. The genetic correlation of
      basal, 1st, 5th partial waves were negative, the others were positive, with the
      litter size and litter size alive. It showed that the reproductive performance of
      Min pigs were not expressed perfectly, as the balance of secretion of
      progesterone did not reach the best. The genetic correlation of all partial waves
      with duration of estrus was negative which supported that the progesterone
      suppresses the estrus. The genetic correlation of 3rd, 5th partial waves were
      stronger than others, but selection for 5th partial wave would make high
      responses than the 3rd wave, because the genetic correlation of 3rd partial wave
      with litter size and litter size alive was positive, therefore, the more
      appropriats method of selection for progesterone was adopted, the better results
      would be achieved in the improvement of indirect selection response for litter
      size.

PMID- 9648400
TI  - [Genetic relationships of Nyctereutes procyonopides: as inferred from random
      amplified polymorphic DNA analysis].
AB  - Random amplified polymorphic DNAs (RAPDs) were used to investigate genetic
      relationships of eight raccoon dogs (Nyctereutes procyonopides). Using 28
      arbitrary primers (10 bp), about 130 RAPD markers were observed in each
      individual. The average, maximum, and minimum genetic distance among 8 raccoon
      dogs are 11.20%, 14.93%, and 2.94% respectively. Our molecular phylogenetic trees
      constructed by UPGMA and NJ methods suggest that those 8 Chinese raccoon dogs may
      be divided into 4 clusters: (1) Guangxi raccoon dog, (2) Anhui raccoon dog, (3)
      Shaanxi raccoon dog, (4) Yunnan and Vietnam raccoon dog. Guangxi raccoon dog is
      more closely related to Anhui raccoon dog than to Yunnan-Vietnam raccoon dog. If
      the Yunnan-Vietnam cluster is a valid subspecies, it is reasonable to give the
      Guangxi, Anhui and Shaanxi clusters the same classification status as that of the
      Yunnan-Vietnam Cluster.

PMID- 9648401
TI  - [Studies on late replication bands of giant panda (Ailuropoda melanoleuca)
      chromosomes].
AB  - Using the cultured giant panda (Ailuropoda melanoleuca) lymphocytes as
      experimental material, we carried out the terminal marking on the chromosomes
      which were in replication by adding BrdU (a final concentration: 10
      micrograms/ml) about four hours before harvesting the cells. The chromosomes
      marked by BrdU were proceeded by staining with acridine orange solution (0.05%),
      irradiated by ultraviolet and counter-stained by Giemsa, we obtained clear
      chromosomes replication patterns. According to the different replication bands,
      every chromosome's characteristics in late replication behavior could be
      identified. In the two X chromosomes of female individual, one X chromosome is
      obviously much later than the other one. Especially in the large area near
      centromere on the long arm of late replicating X chromosome. In the male
      individual, there is also a large area on the long arm of chromosome Y which
      replicates very late, but the end of long arm of chromosome Y replicates much
      earlier.

PMID- 9648402
TI  - [Px gene of rice-field eels primed in situ labeling].
AB  - Peroxidase (Px) gene of rice-field eels (Monopterus albus) was successfully
      localized to the segments of two bivalents, 8q15-q26 and 11q32-q37 with
      digoxigenin labeled primed in situ labeling (PRINS) technique, which is utilized
      for localization of single copy gene of fish for the first time. Our results
      demonstrated the possibility of mapping genes in fish by the DNA probes of other
      species and PRINS technique.

PMID- 9648403
TI  - [Study on the induction of pco promoters from Escherichia coli with copper and
      other metal ions].
AB  - Two copper inducible promoters in the pco determinant of Escherichia coli were
      studied by determining the luciferase activity of report vector pUCD615. The
      results showed that in the absence of pBIN19pco, providing copper resistance
      genes in trans, the maximum induction for both PpcoA lux fusions was observed at
      5 mmol/L CuSO4 and PpcoA box was a stronger promoter than PpcoA long. There were
      two peaks in the bioluminescences of both PpcoE-lux fusions induced with
      increasing copper concentration, the first peak was observed at about 0.5 mmol/L
      CuSO4, the second peak, also the maximum induction, was observed at about 5
      mmol/L CuSO4, and PpcoE long was a stronger promoter than PpcoE box. The results
      indicated that the PpcoE promoter was a much stronger promoter than PpcoA
      promoter. The results also showed that the copper box was very important and
      essential to pco promoters, since both of the Ppco short-lux fusions failed to
      show any luciferase activity when they were induced with copper. In the presence
      of pBIN19pco, the maximum inductions of all of the Ppco-lux fragments were
      observed at 6 mmol/L CuSO4 and they were much higher than those observed in the
      absence of pBIN19pco, and the results also indicated that the cells were able to
      resistant to much higher copper concentration in the presence of pBIN19pco than
      in the absence of that. Zn2+ and Ni2+ could be inducers for all of the fragments
      and Zn2+ was a better inducer than Ni2+, and Cd2+ and Ag+ did not induce the pco
      system.

PMID- 9648404
TI  - E&M coding.

PMID- 9648405
TI  - Cancer risk assessment in the community practice setting.

PMID- 9648406
TI  - Advances in diagnosis and therapies for breast cancer.
AB  - Major achievements in the field of breast cancer research have occurred in the
      last year. Improved treatment options with reduced toxicities, better methods of
      diagnosing disease at a low stage and determining women who are at genetic risk,
      and the prospect of breast cancer prevention will hopefully translate into
      further reductions in breast cancer incidence and mortality.

PMID- 9648407
TI  - Advancements in radiotherapy and improved outcomes in prostate cancer.

PMID- 9648408
TI  - Progress and promise in pediatric oncology.

PMID- 9648409
TI  - Latest trends and applications of stem cell transplantation.

PMID- 9648410
TI  - Current trends in the management of melanoma.

PMID- 9648411
TI  - Head and neck oncology: what's new.

PMID- 9648412
TI  - Hospice resources in south Carolina.

PMID- 9648413
TI  - Why is CDA in the publishing business?

PMID- 9648414
TI  - CDA board approves new fluoride supplementation dosage schedule.

PMID- 9648416
TI  - The changing face of disability insurance and how it affects you.

PMID- 9648415
TI  - New guidelines for antibiotic prophylaxis approved. Canadian Dental Association.

PMID- 9648417
TI  - A Ukraine odyssey.

PMID- 9648418
TI  - Interim storage of avulsed permanent teeth.
AB  - This literature review examines the effects of extra-alveolar duration and
      storage conditions on the healing of the periodontal ligament (PL) of avulsed
      teeth following replantation. A critical assessment of the so-called
      "reconstitution theory" for PL cells is also presented. The ideal treatment for
      an avulsed tooth is immediate replantation (i.e. less than five minutes).
      Unfortunately, immediate replantation is not the norm, and most avulsed teeth
      experience delayed replantation. The greatest risk to the vitality of the PL
      cells attached to the root of an avulsed tooth is desiccation. Not surprisingly,
      storage media affect PL healing. Storing avulsed teeth in an isotonic liquid is
      superior to dry storage. Numerous studies support the use of Modified Eagle's
      Medium, Hank's Balanced Salt Solution (HBSS), ViaSpan, saline, milk, and saliva
      as storage media. A recent study has suggested that chicken egg white may also
      prove to be a suitable storage medium for avulsed teeth. Of these media, only
      saliva is always present at the scene of an accident, however. Milk can usually
      be obtained on short notice, but even 10 minutes of desiccation can affect the
      outcome of replantation. From a practical standpoint, milk packed in ice seems to
      be the best alternative for the temporary storage of avulsed teeth, due to its
      wide availability and the minimal detrimental effects it has on PL cells. There
      is no evidence to support the suggestion that HBSS or any other media will
      "reconstitute" the PL cells when the extra-alveolar duration of avulsed teeth is
      greater than 30 minutes.

PMID- 9648419
TI  - [Endopore: a new generation of implants].
AB  - The Endopore implant system has gained popularity since it was first
      commercialised. Developed at the University of Toronto, its unique design is
      characterized by a partial porous coating and a tapered, truncated-cone,
      endosseous root-form. These features allow for ease of placement, a faster
      healing period, the use of shorter implants, and greater resistance to torque
      (due to bone ingrowth in the porous coat). This article discusses the design and
      fabrication of the Endopore implant. The surgical procedure as well as the main
      advantages of this new type of implant are also considered.

PMID- 9648420
TI  - The part-time clinical instructor in the undergraduate dental clinic.
AB  - Currently, part-time dental instructors do not receive formal training in
      education. According to the recent literature, some instructors may not be aware
      of all the options available to them in the clinic. It has been observed, for
      example, that instructors have demonstrated the greatest effectiveness while
      acting as facilitators rather than as educators. These instructors are able to
      incorporate their position as role models into their teaching. Dental departments
      must understand that the tone established in the clinic has a significant impact
      on the quality of their students' learning experience. This tone arises out of
      open dialogue between instructors and their students. The complexities of
      successful teaching can only be conquered when more information is provided to
      part-time staff.

PMID- 9648421
TI  - Management of accidental and iatrogenic injuries to the dentition.
AB  - This article discusses the restoration of teeth with extensive fractures
      extending beyond the attachment of the periodontal ligament, as well as the
      treatment of iatrogenic perforations observed during post space preparation.
      Various treatment procedures and their limitations are described, based on the
      authors' many years of clinical experience.

PMID- 9648422
TI  - Effects of diversion and reperfusion of pancreaticobiliary juice on amylase
      release from isolated rat pancreas.
AB  - Diversion of pancreaticobiliary juice from the small intestine results in
      resetting of the normal negative-feedback regulation of exocrine pancreatic
      secretion. The mechanism by which this process occurs is not well understood. To
      examine this regulatory process, we investigated the effects of
      pancreaticobiliary juice diversion and reperfusion on exocrine pancreas using
      isolated rat pancreatic acini. Two groups of rats were surgically prepared for
      pancreaticobiliary juice diversion and reperfusion. Both groups received a liquid
      diet via a duodenal cannula and saline by intravenous infusion for 24 hours
      following surgery. Forty-eight hours after the surgery and infusions, the rats
      were sacrificed, and acinar cells were quickly isolated from each pancreas.
      Amylase release from isolated acini was measured in response to doses of
      cholecystokinin octapeptide (CCK-8) and carbachol. Acinar cell receptor binding
      was measured by using CCK-8 labeled with iodine 125 and N-tritium-methscopolamine
      bromide as radioligands. Amylase release in response to both CCK-8 and carbachol
      was significantly decreased in the diversion group when compared with that of the
      reperfusion group. Receptor binding sites of CCK-8 and methscopolamine bromide
      were similar in the diversion and reperfusion groups. The results suggest that
      cholecystokinin- and carbachol-mediated amylase response is affected by
      pancreaticobiliary juice diversion through a process that most likely involves
      alteration of post-receptor-mediated intracellular signaling pathways.

PMID- 9648423
TI  - Spontaneous resolution of a plasma cell granuloma in a 9-year-old.
AB  - A previously healthy 9-year-old white boy presented with a 13-lb weight loss over
      a period of 4 weeks and a 4.5-cm mass in the right lung. Histology was compatible
      with a plasma cell granuloma, which is the most common benign childhood lung
      tumor. Surgical management with segmental or wedge resection is the usual
      standard of care in this situation. However, it has been suggested that with a
      confirmed histologic diagnosis surgical resection is not warranted. This patient
      was managed conservatively. Repeat computed tomography scan 6 weeks later
      revealed significant resolution of the lesion, and at 7 months the lesion had
      totally resolved. Spontaneous resolution of this lesion has been rarely described
      in pediatric populations.

PMID- 9648424
TI  - Emergency departments and abuse: policy issues, practice barriers, and
      recommendations.
AB  - The abuse of women has reached epidemic proportions. There are an estimated 12
      million abused women in the United States. Reported cases of abuse, however,
      range from 2 to 4 million. Less than 15% of these women ever seek medical care.
      Of women who do seek care, an estimated 75% use the emergency department, often
      presenting with complaints not readily suggestive of abuse. Reports indicate,
      however, that emergency departments consistently identify less than 10% of all
      abuse cases. In 1991 and 1992, the Joint Commission on Accreditation of
      Healthcare Organizations established standards for emergency departments to
      develop policies and procedures for the identification, treatment, and referral
      of female and elderly victims of abuse. Virtually all emergency medicine
      professional societies have official policies to encourage development of
      protocols for abuse identification and management. The American Medical
      Association and the Department of Health and Human Services have likewise
      developed guidelines to help emergency departments achieve these national health
      care objectives. Currently, less than 50% of all emergency departments have
      established algorithms to address abused women who present to the emergency
      department for treatment. This article reviews current health policy, examines
      the impediments to the detection of abuse in the emergency department, and
      recommends mechanisms to enhance the awareness of abuse among emergency
      department personnel.

PMID- 9648425
TI  - Use and safety of aspirin in the chemoprevention of colorectal cancer.
AB  - Colorectal cancer is the third leading cause of cancer-related mortality and a
      significant public health problem in the United States. Aspirin and other
      nonsteroidal anti-inflammatory drugs reduced the incidence of colorectal cancers
      and related mortality by 30% to 60% as well as the incidence of colonic adenomas.
      This effect is presumably due to an inhibition of cyclooxygenase 2, an inducible
      enzyme involved in the synthesis of prostaglandins. Prostaglandins are increased
      in colorectal neoplasms. Aspirin's effect appears to be dose related and enhanced
      by long-term exposure. Two prospective studies, however, failed to show a
      protective benefit of aspirin in colorectal cancer. When used long term, aspirin
      has significant adverse effects and is poorly tolerated. The gastrointestinal
      toxicity of aspirin is dose related, but even low doses of aspirin (75 mg per
      day) when used regularly result in significantly higher gastrointestinal
      toxicity, manifested by melena, hematemesis, and peptic ulcer disease, in aspirin
      users compared with nonusers. Furthermore, some studies indicate an increased
      risk of hemorrhagic strokes in aspirin users. Presently, aspirin should not be
      recommended for the primary chemoprevention of colorectal cancer in the general
      population due to significant risks of serious cerebrovascular and
      gastrointestinal adverse effects associated with long-term aspirin use.

PMID- 9648426
TI  - [Antibiotic therapy in eradicating Helicobacter pylori infections].

PMID- 9648427
TI  - [Recent topics on Helicobacter pylori--Historic background and problems caused by
      bacteria].

PMID- 9648428
TI  - [Studies on Helicobacter pylori].

PMID- 9648429
TI  - [Pathophysiological mechanism of Helicobacter pylori infections].

PMID- 9648430
TI  - [Pathophysiological mechanism of Helicobacter infections--host factors].

PMID- 9648431
TI  - [Helicobacter pylori infections in animal models].

PMID- 9648432
TI  - [Gastritis due to Helicobacter pylori].

PMID- 9648433
TI  - [Peptic ulcer due to Helicobacter pylori].

PMID- 9648434
TI  - [Helicobacter pylori and stomach cancer, lymphoma, and MALToma].

PMID- 9648435
TI  - [Helicobacter pylori and non-ulcer dyspepsia].

PMID- 9648436
TI  - [Diseases suspected to have relationship to Helicobacter pylori].

PMID- 9648437
TI  - [Diagnosis of Helicobacter pylori infections by endoscopy, bacterial culture
      method, and rapid urease test].

PMID- 9648438
TI  - [Diagnosis of Helicobacter infections by serodiagnosis, analysis of serum
      pepsinogen, and urea breath tests].

PMID- 9648439
TI  - [Efficacy of antibiotic therapy in eradicating Helicobacter pylori].

PMID- 9648440
TI  - [Problems following antibiotic therapy for eradication of Helicobacter pylori].

PMID- 9648441
TI  - [Present status of vaccine therapy for Helicobcter pylori infection].

PMID- 9648442
TI  - [Topics on Helicobacter pylori (discussion)].

PMID- 9648443
TI  - [Case of diabetic diarrhea successfully treated by cholestyramine].

PMID- 9648444
TI  - [Case of primary aldosteronism associated with heart and kidney failure].

PMID- 9648445
TI  - [Calcified aneurysm of sinus of Valsalva in the aged].

PMID- 9648446
TI  - [Case of acute respiratory failure due to polyarteritis nodosa].

PMID- 9648447
TI  - [Case of tubercular constrictive pericarditis with right atrial thrombosis].

PMID- 9648448
TI  - [Vibrio vulnificus infections].

PMID- 9648449
TI  - [Present status and future prospects in development of blood substitutes].

PMID- 9648450
TI  - [Hyperlipidemia and arteriosclerosis].

PMID- 9648451
TI  - [Changing concept and definition of osteoporosis].
AB  - History of osteoporosis dates back to prehistoric era and no real progress in the
      understanding of osteoporosis was made until 1900 AC when Roentgen discovered X
      ray to make bone visible in vivo. From this time to 1950 when Albright and many
      others opened way to the pathophysiology of osteoporosis as one of the metabolic
      bone diseases, X-ray picture was the only tool to assess osteoporosis. Subsequent
      biochemical, epidemiological and endocrinological approach clarified the risk
      factors and pathophysiology of osteoporosis in the modern age. Treatment and
      prevention of osteoporosis also became feasible based on these development. Such
      a rapid progress in the understanding of osteoporosis also caused an inevitable
      confusion in the concept of osteoporosis.

PMID- 9648452
TI  - [Pathogenesis of osteoporosis and risk factors].
AB  - Osteoporosis is defined as a disease with low bone mineral density (BMD) and the
      increased probability for non-traumatic fractures in elderly. BMD in the elderly
      is theoretically determined by the BMD reached in younger era and the rate of
      bone loss in the later life. Both of peak bone mass and bone loss rate are known
      to be affected by environmental factors as well as genetic factors. In addition,
      both factors are assumed to interact each other. Prevention and treatment of
      osteoporosis would be fascilitated by understanding both of these factors.

PMID- 9648453
TI  - [Genetic studies in osteoporosis].
AB  - Osteoporosis is one of the complex disease which has many responsible fractors to
      develop this disease. Among the causative factors for osteoporosis, genetic
      background is believed as the most important factor for osteoporosis. In 1994,
      Morrison et al reported their pioneering work looking at the close relationship
      between VDR genotype and bone mass. This report has generated a considerable
      amount of interest and conflict. The reasons for these conflicts are depending
      upon the nature of osteoporosis. Namely, the genetic association to the cause of
      osteoporosis is polygenic. Furthermore, the contribution of a gene to achieve low
      bone mass is polyphasic. For example, estrogen-receptor gene polymorphisms may
      show varied importance in the different stage of women's life span. The
      environmental factors may interefere the penetration of a gene effect and the
      presence of the other gene effect may also blunt the effect of the candidate
      gene. To overcome these difficulties in the research work to search osteoporosis
      gene, we have pay keen attention to the selections of the method of gene analysis
      and the subjects. The specific gene marker showed the possibility to predict the
      effect of the treatment of osteoporosis. This may indicate the marker gene itself
      or the other gene(s) linked with this marker gene regulate the biological
      response to the treatment. So, gene markers may utilize not only in the field of
      epidemiological studies but also in clinical practice in near future.

PMID- 9648454
TI  - [Morphology of bone remodeling].
AB  - In this review, first the basic structure of bone and the histological and
      cytological characteristics of bone remodeling are reviewed. Then, topics on the
      ultrastructural and cytochemical characteristics of the biological
      mineralization, such as matrix vesicle and advanced collagen mineralization, are
      discussed. The recent advances in the understanding of the fine structural and
      cytochemical characteristics of bone cells in bone remodeling and their role in
      the regulation of bone metabolism, with special focus on the ultrastructural and
      cytochemical evidences of cell to cell, cell to metrix interaction of bone cells
      are also reviewed.

PMID- 9648455
TI  - [Regulatory mechanisms of bone remodeling].
AB  - Bone tissues continuously renew themselves to maintain their bone volume and
      mechanical strength. Sequence of the cellular events at the site of bone
      remodeling is as follows: (1) Activation; osteoclast progenitors are activated
      and differentiated. (2) Resorption; osteoclasts resorb a certain volume of bone
      by removing bone matrix and mineral. (3) Formation; osteoblasts differentiate and
      form new bone. The cellular coupling in space and time between osteoclastic
      resorption and osteoblastic formation is regulated not only by systemic hormones
      (estrogen, PTH, calcitonin, or vitamin D etc.) and local factors (TGF-beta, BMPs,
      IGFs, prostaglandins, interleukins, or TNF-alpha, etc.), but also by mechanical
      stress. We review the various regulators for bone remodeling and comment on the
      regulatory mechanism of bone remodeling.

PMID- 9648456
TI  - [Recent advances in researches on bone formation--role of BMP in bone formation].
AB  - Recent advances in action of bone morphogenetic protein (BMP), a member of TGF
      beta superfamily, in the differentiation process of mesenchymal cells such as
      osteoblasts, chondrocytes, bone marrow stromal cells and muscle cells have been
      reviewed. BMPs induce osteoblast differentiation of various types of cells
      including undifferentiated mesenchymal cells, bone marrow stromal cells and
      preosteoblasts. BMPs not only inhibit myogenic differentiation but also convert
      differentiation pathway of some myogenic cells into an osteoblast lineage. The
      regulatory mechanism of BMP action discovered in the process of early
      embryogenesis is also reviewed; noggin, chordin and follistatin inhibit BMP
      action by specifically binding to BMPs.

PMID- 9648457
TI  - [Recent advances in biology of bone resorption].
AB  - Bone resorption is a unique process which requires function of highly specialized
      cells, i.e., osteoclasts, Osteoclasts are terminally differentiated multinuclear
      cells that originate from multipotent hematopoietic stem cells and are closely
      related to the monocyte/macrophage lineage. Recent advances in molecular
      biological techniques and development of useful experimental systems both in
      vitro and in vivo have made it possible to identify several factors essential to
      osteoclast differentiation or function under physiological and/or pathological
      conditions. Such factors include transcription factors such as c-Fos and PU.1,
      cytokines such as IL-6 and TNF-alpha, and other various molecules such as
      tyrosine kinases and adhesion molecules. This review will focus on recent
      progress in our understanding of osteoclast biology.

PMID- 9648458
TI  - [Localization and function of calcium-sensing mechanism in bone cells].
AB  - Elevation of extracellular calcium has been shown to inhibit osteoclastic bone
      resorption and stimulate proliferation and chemotaxis of osteoblasts. Therefore,
      calcium released by bone resorption may have important roles in the coupling of
      bone resorption and bone formation. Although both osteoclasts and osteoblasts
      have calcium-sensing mechanisms, the responsible molecule in these cells seems to
      be different. Functional and histological studies show that calcium-sensing
      mechanism in osteoclasts is a ryanodine receptor-like molecule in plasma
      membrane. In contrast, calcium-sensing mechanism in osteoblasts has similar
      functional property to parathyroid calcium-sensing receptor (CaSR), but is a
      different molecule from CaSR. In addition, several bone marrow cells express
      CaSR. The elucidation of the identity and the physiological roles of these
      calcium-sensing mechanisms would give us a more clear view of bone remodeling.

PMID- 9648459
TI  - [Bone matrix proteins].
AB  - Bone matrix is composed of collagen and non-collagenous proteins. The collagen is
      mainly type I collagen. Characteristics of bone collagen are in posttranslational
      modifications and utilization of transcriptional elements in the promoter. The
      non-collagenous proteins are acidic Ca-binding proteins: bone Gla protein(BGP),
      bone sialoprotein (BSP), osteopontin, osteonectin etc. BGP and BSP are specific
      to bone, and other proteins are present also in non-mineralized tissues. BGP
      functions in suppression of excessive mineralization. BSP and osteopontin are
      sialoproteins containing a RGD cell-attachment sequence and poly(acidic amino
      acid) sequences. BSP is present in sites of bone formation. Osteopontin is
      involved in attachment of osteoclasts to bone surface.

PMID- 9648460
TI  - [CBFA1/PEBP2 alpha A].
AB  - A transcription factor, Cbfa1/Pebp2 alpha A, which belongs to runt-domain gene
      family, is preferentially expressed in the osteoblast lineage. Cbfa1/Pebp2 alpha
      A-deficient mice lacked both intramembranous and endochondral ossification
      completely. The differentiation of osteoblast was blocked, and the maturational
      disturbance of osteoclasts was also observed in the mutant mice. Further, the
      Cbfa1/Pebp2 alpha A expression in nonosteoblastic cells induced osteoblastic
      markers in vitro. These data demonstrate that Cbfa1 is an essential transcription
      factor for osteoblast differentiation and bone formation. Heterozygously mutated
      mice in the Cbfa1/Pebp2 alpha A locus showed the similar phenotype with
      cleidocranial dysplasia, which is an autosomal inherited disease. And the
      mutations of CBFA1/PEBP2 alpha A locus were identified in the patients with
      cleidocranial dysplasia.

PMID- 9648461
TI  - [Osteoclastogenesis inhibitory factor (OCIF)/OPG].
AB  - A novel cytokine termed osteoclastogenesis inhibitory factor (OCIF) was purified
      to homogeneity from conditioned medium of human embryonic lung fibroblasts. OCIF
      is a heparin-binding basic glycoprotein with Mr of 60 kDa for a monomer and 120
      kDa for a homodimer. OCIF specifically inhibits osteoclastogenesis in vitro and
      increases bone mineral density and bone volume in normal rats. The cloning of
      OCIF cDNA revealed that OCIF is a soluble member of the tumor necrosis factor
      receptor (TNFR) superfamily consisting of four cystein-rich domains, two death
      domain homologous regions (DDHs), and C-terminal basic domain. Mutational
      analysis of OCIF revealed that N-terminal portion of OCIF consisting of four
      cystein-rich domains is sufficient to inhibit osteoclastogenesis. OCIF inhibits
      osteoclastogenesis by binding to the sites expressed on osteoblastic cells and
      interrupting cell-to-cell signaling between osteoblastic cells and osteoclast
      progenitors.

PMID- 9648462
TI  - [Cloning and expression of 25-hydroxyvitamin D3-1 alpha-hydroxylase gene].
AB  - A full-length cDNA for the rat kidney mitochondrial cytochrome P450 mixed
      function oxidase, 25-hydroxyvitamin D3-1 alpha-hyroxylase, was cloned from a
      vitamin D-deficient rat kidney cDNA library and subcloned into the mammalian
      expression vector pcDNA 3.1(+). When 1 alpha-hydroxylase cDNA was transfected
      into COS-7 cells, they expressed 25-hydroxyvitamin D3-1 alpha-hydroxylase
      activity. The sequence analysis showed that 1 alpha-hydroxylase cDNA consisted of
      2469 bp in length and contained an open reading frame encoding 501 amino acids.
      The expression of 1 alpha-hydroxylase mRNA was greatly increased in the kidney of
      vitamin D-deficient rats. In rats with the enhanced renal production of 1 alpha,
      25-dihydroxyvitamin D3 (rats fed a low Ca diet), expression of 1 alpha
      hydroxylase mRNA was greatly enhanced in the renal proximal convoluted tubules.
      These results clearly demonstrate that the expression of 1 alpha-hydroxylase is
      regulated at a transcriptional level. The DNA flanking the 5'-sequence of the
      mouse 1 alpha-hydroxylase gene has been cloned and sequenced. The promoter has 3
      potential CRE sites, 2 perfect and 1 imperfect AP-1 sites, while no DR-3 was
      detected. Parathyroid hormone stimulates this promoter-directed synthesis of
      luciferase by 17-fold, while forskolin stimulates it by 3-fold. These results
      indicate that parathyroid hormone stimulates 25-hydroxyvitamin D3-1 alpha
      hydroxylase by acting on the promoter of the 1 alpha-hydroxylase gene.

PMID- 9648463
TI  - [Establishment of cultured cells sustaining bone metabolism and their application
      for osteogenesis in vivo].
AB  - Osteoblasts, osteoclasts and osteocytes respectively, play important roles
      responsible for bone metabolism. These cells were cultured in vitro by many
      researchers, and considerably contributed to recent basic research on bone
      metabolism. Especially MC3T3E1-cells, cloned mouse osteoprogenitor cells, can
      perform bone formation-process in culture. Furthermore, several osteoblastic cell
      line including our SaM-1 cells were established from rodent calvaria,
      osteosarcoma, and human bone or periosteum. Also, osteoclasts are actually formed
      from human bone marrow cells, as well as rodent bone marrow cells, recently. It
      has become effective that the results obtained by using normal human cultured
      cells apply to human bone metabolism in vivo.

PMID- 9648464
TI  - [Criteria and classification for diagnosis of osteoporosis in Japan].
AB  - Osteoporosis has become one of the most serious medical and social problems in
      Japan, as the number of elderly people is increasing. Osteoporosis should be
      diagnosed early and treated properly to maintain the patients' quality of life
      before associated fractures occur. The Japanese society for bone and mineral
      research prepared the criteria for diagnosis of osteoporosis in 1995 and modified
      them in 1996. Here, we explained the 1996's modified criteria and described the
      actual way to diagnose osteoporosis. Low bone mass is evaluated by radiographic
      osteopenia or bone mineral density in lumbar body. We have to exclude the other
      disorders showing low bone mass.

PMID- 9648465
TI  - [Recent development and clinical application of bone mineral measurements].
AB  - Over the past decade, methodologies for the assessment of bone mineral density
      have markedly progressed, so that any sites of the skeleton now can be measured
      with high degree of accuracy and precision with safety. The number of devices
      distributed in Japan rapidly increased for the last 5 years and the total number
      installed nationwide reached over 7000 as with 1998. There are variety of
      techniques: microdensitometry (MD) or radiographic absorptiometry (RA), single X
      ray absorptiometry (SXA), dual X-ray absorptiometry (DXA), quantitative CT (QCT),
      peripheral QCT, and quantitative ultrasonometry (QUS). There are, however, no
      such single technique as to fulfill the entire clinical requirements, since the
      time of initiation of bone loss, and the speed of bone loss are quite different
      from site to site of the skeleton, so that the correlations of bone density
      measured by each technique are not sufficiently high (gamma = 0.5-0.8) to predict
      BMD of other bones by measuring one bone. Since the relatively large amounts of
      data on the prediction of fracture (hip, spine and others) by these techniques
      have been accumulated, a specific guideline regarding the appropriate application
      of these techniques, including multiple combination measurements, should be
      established based on the worldwide consensus.

PMID- 9648466
TI  - [Photodensitometry].
AB  - Photodensitometry was developed by several investigators. This technique makes
      possible bone mass measurements from radiographs of the peripheral skeleton, most
      commonly the metacarpal and phalangeal bones. More recently, with the advent of
      computerized image processing, photodensitometry has become more precise and
      gained new respect for use in the diagnosis of osteoporosis. In addition, recent
      studies in which radiographic absorptiometry was used have demonstrated that the
      detection of accelerated bone loss in the early menopause with this technique is
      comparable to other densitometry techniques. Being cost effective, easy to
      perform, and universally available, all makes photodensitometry an increasing
      attractive option for non invasive bone assessment in both research and clinical
      practice.

PMID- 9648467
TI  - [X-ray absorptiometry].
AB  - Bone mass measurements are essential in the diagnosis of osteoporosis, the
      monitoring of its progression, and the evaluation of therapeutical responses.
      Among various methods of bone mass measurements, single- and dual-X-ray
      absorptiometry, SXA and DXA, have shown excellent fundamental performance. In
      this paper, the principles of SXA and DXA; i.e., factors of fundamental
      performance, such as precision, data-acquisition, and radiation dose, the
      practice of DXA, recent advances in DXA, such as the lateral spine scan, the
      measurement of body composition, application to BMD measurement of the bones of
      small animals and at sites of metal implants, morphometry of the spine, and
      geometrical measurement in the proxial femur, and clinical applications to
      osteoporosis were particularly reviewed.

PMID- 9648468
TI  - [Ultrasound bone densitometry of os calsis].
AB  - In the last couple of years, Ultrasound bone densitometry (QUS: Quantitative
      ultrasound) have been developed which allow the assessment of fracture risk
      caused by osteoporosis. QUS are particularly promising since they are simple,
      inexpensive, portable, non-invasive and they do not subject the patient to any
      ionising radiation. Additional investigations that assess innovative QUS
      techniques in well defined research settings are important to determine and
      utilize the full potential of this technology for the benefit of early detection
      and monitoring of osteoporosis.

PMID- 9648469
TI  - [Quantitative X-ray computed tomography].
AB  - Quantitative X-ray Computed Tomography (QCT) has an advantage to be able to
      determine three-dimensional bone density of lumbar vertebral body compared with
      dual energy X-ray absorptiometry (DXA) method. We introduced the high
      reproductable QCT method as a simplified manual operation avoiding simultaneous
      imaging of both patients and bone mass phantoms. The coefficient of variation of
      values measured by phantom study was 0.6% for 7 years in our hospital. In
      measuring of 144 healthy Japanese women, the bone mineral density of lumbar spine
      was most likely to be decreased linealy with age.

PMID- 9648470
TI  - [Analysis of trabecular microstructure using micro-computed tomography].
AB  - Micro-computed tomography (micro-CT) is a special CT to examine biopsy bone
      samples or small animal bones in vitro, and it can provide high resolution images
      (20-30 microns) precisely representing the two-dimensional and three-dimensional
      microstructure of the trabecular bone. The quantification of trabecular
      connectivity and anisotropy, which is believed to be strongly related to the bone
      strength, can be done with micro-CT. In comparison with histomorphometry and
      scanning electron microscopy, micro-CT has the advantage of requiring less
      efforts and time. Besides, micro-CT provides higher resolution than micro
      magnetic resonance. So far, micro-CT is believed to be the best method to analyze
      the three-dimensional structure in vitro.

PMID- 9648471
TI  - [Biochemical markers of bone metabolism].
AB  - Markers of bone metabolism can be utilized for selection of treatment and/or
      evaluation of the treatment, and possibly decision-making to start treatment.
      Resorption markers are sensitive to detect changes in bone metabolism but show
      higher day-to-day variation, and formation markers are less sensitive but show
      less fluctuation. Among these markers, deoxypyridinoline, NTx, and CTx are
      utilized for short-term judgement of efficacy during the early phase of anti
      resorptive treatment, such as bisphosphonate and hormone replacement therapy. The
      coefficients of day-by-day variations in these resorption markers are 8-14%.
      Thus, 20 (approximately 30)% or more change in marker levels may be necessary to
      detect the efficacy in individual patients on anti-resorptive therapy. The
      formation markers can be utilized for monitoring the degree of excessive
      suppression during the late phase of treatment by anti-resorptive treatment,
      possibly later than 6 months following initial treatment.

PMID- 9648472
TI  - [Guidelines for clinical use of drugs for involutional osteoporosis].
AB  - Guidelines for clinical use of drugs for involutional osteoporosis will be
      released soon in Japan. Seven different types of drugs for osteoporosis are in
      market for clinical use in Japan. Those includes calcium, estrogens, anabolic
      steroids, calcitonins, active vitamin D3, ipriflavon, and etidronate. The
      guidelines recommend to clarify the risk factors in each patient before to start
      administration of drug. Patients with osteopenia are basically recommended to be
      followed without any drug treatment, but, patients with osteoporosis are
      generally recommended to be treated with drug after evaluation of risk factors.
      After menopause, inhibitors of bone resorption would be recommended as a first
      choice drug. For monitoring effects of treatment, bone mass measurement is so far
      the first choice, but bone metabolic markers would be used as well.

PMID- 9648473
TI  - [Treatment of osteoporosis by active vitamin D].
AB  - Supplementation of active vitamin D has been thought to be reasonable for those
      who convert insufficiently vitamin D to active form, especially for senile
      persons. Treatment of osteoporosis by vitamin D are accepted as not only
      supplementation of vitamin D but also direct activation of bone turnover. Several
      previous clinical trials suggest active vitamin D prevents fractures more
      effectively rather than the increase of the bone mass. The calcium intake of
      Japanese people is less than that of Western countries, and many of Japanese have
      the vitamin D receptor genotype which is more responsive to vitamin D. Therefore,
      it is probable that active vitamin D is more effective for Japanese than Western
      people.

PMID- 9648474
TI  - [Calcitonin].
AB  - Calcitonin is a potent inhibitor of osteoclastic bone resorption and has been
      widely used for the treatment of osteoporosis. Nasal calcitonin, instead of
      injectable form, is more popular in Europe and United States, while only
      injectable form has been approved in Japan. The regimen, dose, frequency is
      remarkably different from study to study, and the standard regimen has not been
      established for osteoporosis. Fifty to 100 units of salmon calcitonin has been
      used daily intramuscularly in Europe. Recent trial using nasal calcitonin has
      shown the similar effects on the bone as the injectable form although the actual
      resorptionis not so high. In Japan, once weekly 20 units if eel calcitonin
      analogue injection has been approved for osteoporosis. After administration in
      the form of either nasal or injectable preparation, peak serum concentration
      reaches more than 100 pg/ml, far exceeding 10(-11) M, at which level osteoclast
      bone resorption is rapidly impaired with disappearance of actin ring formation.
      It is reflected by the decrease of urinary pyridinoline cross-links excretion.
      Consecutive treatment with calcitonin reduces the calcitonin receptors on the
      surface of osteoclasts as well as osteoclast precursors, while they are still
      TRAP positive, suggesting that they retain bone resorbing activity. That may be
      one of the mechanisms of escape phenomenon. We are not sure whether daily
      administration of calcitonin can avoid the escape phenomenon and can maintain the
      bone volume. The standard preparation should be determined by the longer clinical
      trials with new bone markers and bone mass measurement as the endpoints.

PMID- 9648475
TI  - [Role of estrogen in the pharmacotherapy of osteoporosis].
AB  - Since approval by the Food and Drug Administration of bisphonate and calcitonin
      for the prophylaxis of osteoporosis, estrogen preparations are no longer the only
      drugs effective against this disease. However, because of their effects on
      systems other than bone, estrogens remain the gold standard of osteoporosis
      therapy in postmenopausal women, and health care workers should reacknowledge the
      benefits of estrogen therapy. Although several recent, multicenter double-blind
      studies have reported that estrogens increase bone mineral density (BMD) and
      prevent fractures, further substantiating their clinical efficacy, the effects of
      estrogens on BMD and fracture risk can vary widely among individuals. Rather than
      being used indiscriminately, estrogens should therefore be used in selected
      patients most likely to benefit from such therapy. Treating such patients will
      improve drug compliance, promote continued treatment, and therapy firmly
      establish the role of estrogen therapy.

PMID- 9648476
TI  - [Vitamin K2].
AB  - Vitamin K2 is a known vitamin to promote post-translational modification of
      vitamin K-dependent protein such as osteocalcin and blood coagulation factors.
      The effects of vitamin K2 on cortical bone mineral density in osteoporosis has
      been shown in the phase III DBT trial which had been reported several years ago.
      However, until now there is no available data regarding to the effect of vitamin
      K2 on vertebral bone mineral density (LBMD) and on fracture prevention. Thus, a
      two years randomized open trial to examine the effects of vitamin K2 on LBMD and
      the fracture prevention in a total of 167 osteoporotic patients had been carried
      out. The LBMD in vitamin K2 treated group was maintained for 2 years while, that
      in the control group was deceased to -3% during 2 years observation. The
      vertebral fracture incidence in the control group was 0.212 +/- 0.038 events/year
      and that in the treated group was 0.098 +/- 0.029 (p = 0.0186). Vitamin K2
      treated group showed significantly lower Glu-osteocalcin level suggesting that
      vitamin K2 contributed to increase in post-translational modification of
      osteocalcin. When the treated group was divided into two groups: Group 1 showed
      low serum Glu-osteocalcin level and Group 2 maintained high Glu-osteocalcin level
      despite vitamin K2 administration. The LBMD in group 1 significantly higher than
      that in the Group 2. This may indicate that sufficient tissue supply of vitamin
      K2 is the limiting factor to increase in LBMD. Furthermore, patients with Apo E4
      phenotype showed less response in LBMD comparing to that in the patients without
      Apo E4. In conclusion, vitamin K2 is effective to maintain trabecular BMD in
      osteoporosis and effectively prevent future fracture. However, some part of the
      patients didn't respond to vitamin K2 treatment. Therefore, we have to develop
      the more practical way(s) to predict the effectiveness of vitamin K2 treatment in
      osteoporosis.

PMID- 9648477
TI  - [Bisphosphonates: pharmacology and use in the treatment of osteoporosis].
AB  - Bisphosphonates are attractive antiresorptive drugs for osteoporosis. The only
      compound available in Japan is the first-generation bisphosphonate, etidronate.
      Etidronate adsorbes to the surface of hydroxyapatite crystals, and can slow bone
      mineralization and inhibit bone resorption. It has a narrow therapeutic window
      between these two actions, so that long-term continuous administration is not
      feasible. The intermittent use of etidronate produces a positive effect on bone
      mass. But the response varies directly with the rate of bone turnover at
      baseline. In high turnover osteoporosis there could be a gain in bone mass, but
      it reaches a plateau after 2 to 3 years. In normal or low turnover osteoporosis
      bone mass is stabilized but does not increase. However, the long-term effect of
      bisphosphonates on bone strength is not known.

PMID- 9648478
TI  - [Ipriflavone].
AB  - Ipriflavone (7-isopropoxyisoflavone), a non-hormonal isoflavone derivative, is
      currently used in several countries for prevention and treatment of
      postmenopausal osteoporosis. This compound is devoid of estrogenic activity in
      humans, but increases the activity of estrogens. Ipriflavone has been shown to be
      effective in reducing bone turnover rate mainly through an inhibition of bone
      resorption, and has been effect to stimulate of bone formation. Inhibitory effect
      of ipriflavone on bone resorption has been demonstrated both directly by the
      activation of mature osteoclast and the formation of new osteoclasts by
      stimulating estrogen-induced calcitonin secretion by thyroids in vivo. There are
      some evidence that ipriflavone has direct effect on bone formation. Several
      clinical studies have demonstrated that bone mineral density (BMD) was increased
      or maintained in patients treated with ipriflavone. Recently, a large
      multicentral study, Ipriflavone Multicenter European Fracture Study (IMEFS), was
      designed in order to investigate the efficacy of ipriflavone on the prevention of
      vertebral and the effect on BMD in women with postmenopausal osteoporosis.

PMID- 9648479
TI  - [Recent progress in orthopaedic managements of osteoporosis-related fractures].
AB  - Recent progress in orthopaedic treatment of osteoporosis-related fractures was
      reviewed. In the femoral neck fractures, the bipolar prosthesis reduces
      acetabular erosion or central migration, and press-fit stem or cemented stem
      lowers the incedence of the stem sinking. In thorocanteric fractures, compression
      hip screws are most commonly used, however, in the cases of unstable fractures
      with severe osteoporosis, it is difficult to start weight-bearing within a few
      weeks of surgery because varus deformites or translations at the fracture site
      sometimes occur. To avoid this disadvantage, the gamma nail has been found to be
      more effective. In paralysis due to burst fractures of the osteoporotic spine,
      surgical decompression and spinal instrumentation is the established response. A
      special orthosis named 'rucksack type orthosis' has been devised and is used for
      patients who have back pain due to anterior bending posture of the trunk. In
      distal radius fractures, external fixators are now more frequently used.

PMID- 9648480
TI  - [Physical training].
AB  - Physical training repairs bone structures and increases bone mass as well as the
      most effective medicine, through inducing piezo-electric potential and
      stimulating osteoblastic activity. Although gain of bone mass depends on duration
      and intensity of mechanical loading, researches have shown that daily 30 minutes'
      mild training such as walking has positive effect on increasing bone mass, even
      in elderly persons. Compared with calcium intakes or sun exposure, habits related
      to bone metabolism, physical activity is significantly greater to increase bone
      mass. Interestingly, it is apparent in our study that habitual stroll walks of
      older age groups prevent the falls which is another risk of their fracture in the
      extremities.

PMID- 9648481
TI  - [Nutritional therapy].
AB  - Osteoporosis is one of the life style related diseases. Therefore, from the
      viewpoint of prevention, daily diet and nutrient intake are important. An
      adequate intake of calcium together with nutrient balance plays an essential role
      in maintaining and promoting health and preventing osteoporosis. Moreover, prior
      to nutritional therapy, it is essential to understand the current nutritional
      status and dietary habits of the individual.

PMID- 9648482
TI  - [Epidemiology of osteoporosis: incidence, prevalence, and prognosis].
AB  - Though the exact and cumulative incidence of osteoporosis has not been examined,
      using the criteria that osteoporosis is defined by a decrease of bone mineral
      density (BMD) below 70% from young adult mean (YAM), the prevalence of
      osteoporosis among the Japanese women can be estimated as to be more than either
      30% (by spinal BMD) or 37% (by femoral BMD) in 60's, 37% or 64% in 70's, and 42%
      or 90% in 80's, respectively. The total number of osteoporosis among the women
      with age 50 and over can be also estimated as to be either about 5 million (by
      spinal BMD) or 8.5 million (by forearm BMD). National survey shows that the ratio
      of people receiving treatment for osteoporosis is 34.5 per 1,000 among the
      elderly with age 65 and over. In addition, both functional transition and
      survival rate of discharged patients with osteoporotic hip fracture are discussed
      as prognosis of osteoporosis.

PMID- 9648483
TI  - [Epidemiology--risk factors and preventive strategy].
AB  - Many factors, including age, sex, menopause, genetic makeup, calcium intake, and
      physical exercise, influence the development of osteoporosis. Bone density is a
      major risk factor for fracture at spine and hip. However, risk of hip fracture is
      affected by factors not limited to bone strength, for example, factors related to
      falling. These risk factors can be classified as those that are controllable and
      those that are not. Although one has uncontrollable risk factors, the risk of hip
      fracture can be decreased by reducing the controllable risk factors. To prevent
      osteoporosis and fracture, it is necessary to be familiar with an individual's
      risk factors and offer guidance to reduce the controllable risks. Maintaining or
      increasing bone mass are essential for those with uncontrollable factors.

PMID- 9648484
TI  - [Glucocorticoid-induced osteoporosis--mechanisms and preventions].
AB  - It has been well known that patients with Cushing's syndrome have frequently
      osteoporosis or bone loss due to excess endogenous glucocorticoids and also
      osteopenia or osteoporosis is commonly observed in patients with long-term
      glucocorticoid therapy. In this paper, the mechanisms involved in bone loss in
      Cushing's syndrome and glucocorticoid-induced osteoporosis were demonstrated. In
      the patients with Cushing's syndrome, excess endogenous glucocorticoids increase
      bone resorption and decrease bone formation and also act to depress intestinal
      calcium absorption and increase urinary calcium excretion, leading to
      compensatory stimulation of parathyroid hormone secretion. Then, parathyroid
      hormone stimulates bone resorption. Thus, secondary osteoporosis is commonly
      observed due to excess glucocorticoid. Finally, preventions and managements for
      glucocorticoid-induced osteoporosis were discussed.

PMID- 9648485
TI  - [Secondary osteoporosis and its treatment--diabetes mellitus].
AB  - Japanese epidemiological study showed higher frequency of osteopenia/osteoporosis
      in diabetic patients as compared with sex- and age-matched control. The mechanism
      by which bone loss occurs in diabetic patients could be explained by a reduction
      of insulin/insulin-like growth factor-I action, sustained hyperglycemic state, a
      generation of advanced glycosylation end-products, and diabetic complication such
      as neuropathy, nephropathy and myopathy. Osteoblast deficit is hypothesized to
      play a major role in the occurrence of diabetic osteopenia. Besides the
      deficiency of insulin and insulin-like growth factor-I, we demonstrated that
      sustained hyperglycemia alone causes suppression of osteoblast proliferation and
      its response to parathyroid hormone and 1 alpha, 25-dihydroxyvitamin D,
      Hyporesponse of osteoblast to 1 alpha, 25-dihydroxyvitamin D, was also confirmed
      in diabetic patients as reflected by a reduction in an incremental response of
      serum osteocalcin during 1 alpha, 25-dihydroxyvitamin D administration. The
      regimens having stimulatory effect on bone turnover, such as intermittent PTH
      therapy and vitamin D, are recommended to treat diabetic osteopenia, besides
      improvement of diabetic control state.

PMID- 9648486
TI  - [Bone changes in thyrotoxicosis].
AB  - Thyroid hormone (T3) is essential for normal bone growth and bone metabolism. T3
      stimulates bone formation directly through T3 receptors in osteoblasts. T3 also
      stimulates bone resorption by osteoclasts probably secondary through osteoblasts.
      In thyrotoxicosis accelerated bone formation and resorption resulted in high turn
      over bone loss. Bone metabolic markers elevate reflecting thyrotoxic state.
      Normalizing thyroid hormone level at least partially restore bone mineral
      content. In patients under thyroid hormone replacement therapy or TSH suppression
      therapy TSH and free thyroid hormones should be monitored to prevent unnecessary
      bone loss. Especially in postmenopausal women with thyrotoxicosis or thyroid
      hormone therapy the assessment of bone mineral content is required.

PMID- 9648487
TI  - [Hyperparathyroidism and its management].
AB  - Hyperparathyroidism (HPT), resulting from the excess of endogenous parathyroid
      hormone is cited as one of diseases which cause secondary osteoporosis. HPT
      consists of primary (1 degree) and secondary (2 degrees) HPT, resulting mainly
      from chronic renal failure (CRF). HPT is easily distingishable from primary
      osteoporosis by biochemical measurements. Parathyroidectomy (PTX) is the only
      option available for the radical cure of 1 degree HPT and more than 10% increase
      in bone mass occurs after PTX. On the other hand, dietary phosphorus restriction,
      phosphorus binders, active vitamin D3 metabolites are useful for 2 degrees HPT
      due to CRF. When these treatments are not effective to inhibit PTH secretion
      adequately, oral active vitamin D3 pulse therapy, PTX and percutaneous ethanol
      injection therapy should be considered.

PMID- 9648488
TI  - [Osteoporosis in rheumatoid arthritis].
AB  - Patients with rheumatoid arthritis (RA) develop both periarticular and
      generalized osteoporosis. Periarticular osteopenia in appendicular bones occurs
      early in the course of RA and is one of the earliest radiological signs of RA. An
      uncoupled state in bone resorption-formation linkage, contributes to the
      development of periarticular osteopenia and it might be mediated through an
      increased productions of cytokines and prostaglandins by synovium and bone
      marrow. Accordingly, early suppression of rheumatoid synovitis is necessary for
      the prevention of periarticular osteopenia. Generalized osteoporosis is also
      common in RA and leads to increased risk of fractures. Generalized osteoporosis
      considered to be multifactorial and factors contributing to lumbar osteoporosis
      might be different from those to loss of appendicular bones, such as femur and
      radius. Corticosteroids and menopausal state are important risk factors for
      lumbar osteoporosis. Rheumatoid activity and reduced physical activity are also
      important determinants. According to the previous studies, however, the influence
      of functional impairment is more prominent in the femoral BMD compared to spinal
      BMD. In addition to control of RA and maintenance of physical activity, hormone
      replacement therapy (HRT) and bisphosphonate are possible agents for the
      treatment of osteoporosis in RA patients, especially postmenopausal women.

PMID- 9648489
TI  - [Hepatic osteodystrophy].
AB  - Bone thinning causing both fractures and severe pain not associated with
      fractures has been recognized in patients with chronic liver diseases. The
      patients most commonly affected are those with primary or secondary biliary
      cirrhosis, but those with alcoholic liver disease and cirrhosis after active
      chronic hepatitis may also be involved. Chronic liver disease has also been
      recognized as an important cause of osteoporosis in both sexes, with the
      mechanism thought to be a combination of calcium and/or vitamin D. The 9.1%
      patients with chronic active hepatitis accompanied with osteodystrophy. But 50%
      cirrhotic patients accompanied with osteodystrophy. Bone densitometry was
      determined by Digital Image Processing Method (Osteodystrophy < mean-2SD: age-
      and sex-matched normal value). Serum levels of osteocalcin (BGP) and parathyroid
      hormone (PTH) in patients of hepatic cirrhosis without osteodystrophy were lower
      than those with osteodystrophy. These results were suggested that hepatic
      osteodystrophy was rapidly turnover osteodystrophy. To function physiologically,
      vitamin D must be hydroxylation in liver to 25-(OH)-D and subsequently by the
      kidney to 1 alfa, 25-(OH)2-D. Osteodystrophy associated with hepatic cirrhosis is
      due to a defect in the 1 alfa-hydroxylation by the kidney rather than a hepatic
      hydroxylation defect. 1 alfa OH-D3 is very useful for treatment for hepatic
      osteodystrophy.

PMID- 9648490
TI  - [Secondary osteoporosis in gynecology].
AB  - Several diseases and medications are known to induce secondary osteoporosis.
      Among them, same situations are related to gynecological field. They include
      Turner's syndrome, anorexia nervosa, ovarian dysfunction, oophorectomy, GnRH
      agonist therapy, and osteoporosis associated with pregnancy. We briefly describe
      these secondary osteoporosis in this article as follows. Several studies have
      found osteoporosis to be a common complication of Turner's syndrome and hormone
      replacement therapy has been used as a possible management; in anorexic patient,
      low body weight, prolonged amenorrhea, early onset of anorexia nervosa, and
      hypercortisolism have been reported to be risks for bone demineralization; since
      oophorectomy which is a common intervention in gynecology leads osteoporosis, it
      is important to prevent osteoporosis caused by surgery as well as postmenopausal
      osteoporosis; GnRH agonist, which induces estrogen deficient state and affect
      bone mass, is commonly used as a management for endometriosis and leiomyoma of
      uterus; associated with pregnancy, post-pregnancy spinal osteoporosis and
      transient osteoporosis of the hip are clinically considered to be important and
      heparin therapy and magnesium sulfate therapy are commonly employed during
      pregnancy, affecting calcium homeostasis.

PMID- 9648491
TI  - [Hypogonadism and osteoporosis].
AB  - Hypogonadism, whether caused by primary gonadal failure or secondary gonadotropin
      deficiency, is associated with osteoporosis. Even gonadotropin-releasing hormone
      therapy for endometriosis causes a decrease in bone mineral density by reducing
      serum estradiol level. Recent interesting studies of a male patient with a
      nonsense mutation in the estrogen receptor gene, a girl with missense mutation in
      the aromatase gene, and knock-out mice targeting estrogen receptor gene suggest
      that estrogen is very important to maintain normal bone density even in a male.
      Androgen deficiency increase risk for osteoporosis, but estrogen may compensate
      for it, since osteoporosis is not remarkable in patients with androgen
      resistance. Growth hormone deficiency and hyperprolactinemia are also related to
      gonadal function and thus bone metabolism.

PMID- 9648492
TI  - [Dysregulation of mucosal immunity and inflammatory bowel diseases].
AB  - Normal mucosal immunity is regulated in a delicate balance between up- and down
      regulatory responses to dietal or bacterial antigens. Recent studies demonstrated
      that pathogenesis of inflammatory bowel disease could be dysregulation of the
      balance of mucosal immunity. Recent advances in animal models of inflammatory
      bowel disease, pathogenic roles of mucosal immunoregulatory T cells, cytokines
      and intestinal flora are reviewed.

PMID- 9648493
TI  - [The control of brain tissue temperature and stimulation of dopamine-immune
      system to the severe brain injury patients].
AB  - The recovery of injured neurons in primely brain damage, neuroprotection to the
      secondary brain damage (such as brain edema, brain ischemia, free radicals,
      neuroexcitation and ICP elevation), activation of gene-tropic regeneration, and
      prevention of apobiosis are major targets on the management of severe brain
      injury. However, excess release of catecholamines (catecholamine surge) make a
      very difficult to control of cerebral hypoxia by changes of systemic blood
      circulations. Mild cerebral hypothermia is only one method to prevent of these
      catecholamines surge. We developed new technique, cerebral hypothermia that
      control brain tissue temperature at 32-34 degrees C with more than 800 ml/min.
      oxygen delivery at acute stage. Combination therapy with these cerebral
      hypothermia and replacement of cerebral dopamine-pituitary hormone-estrogen was
      very successful to prevent of vegetation after severe brain injury.

PMID- 9648494
TI  - [The 40th annual meeting of the Japanese Society of Child Neurology. June 4-6,
      1998. Yokohama, Japan. Abstracts].

PMID- 9648495
TI  - [Montelukast--a new building block in the therapy of bronchial asthma.
      Introductory Symposium, MSD Sharp & Dohme GMBH. Telfs (Austria) 6-8 March 1998].

PMID- 9648496
TI  - [New perspectives in the treatment of bronchial cancer. Pan-European Lung Cancer
      Forum: "New perspectives on the Management of Lung Cancer". Sitges/Barcelona, 14
      March 1998].

PMID- 9648497
TI  - Dengue.

PMID- 9648498
TI  - WHO meeting on maternal and neonatal pneumococcal immunization.

PMID- 9648499
TI  - Global leprosy distribution in 1998.

PMID- 9648500
TI  - Overview of evolutionary aspects of omega 3 fatty acids in the diet.

PMID- 9648501
TI  - Dietary intake of long-chain polyunsaturated fatty acids during the paleolithic.

PMID- 9648502
TI  - Omega 3 fatty acids and cardiovascular disease.

PMID- 9648503
TI  - Regulatory effects of polyunsaturates on bone modeling and cartilage function.

PMID- 9648504
TI  - Omega 3 fatty acid status in patients with retinitis pigmentosa.

PMID- 9648505
TI  - Production of docosahexaenoic acid from microalgae and its benefits for use in
      animal feeds.

PMID- 9648506
TI  - Production of docosahexaenoic acid-enriched poultry eggs and meat using an algae
      based feed ingredient.

PMID- 9648507
TI  - Designer eggs and their nutritional and functional significance.

PMID- 9648508
TI  - Poultry-based alternatives for enhancing the omega 3 fatty acid content of
      American diets.

PMID- 9648509
TI  - Single cell oil sources of docosahexaenoic acid: clinical studies.

PMID- 9648510
TI  - Omega 3-enriched pork.

PMID- 9648511
TI  - Enrichment of beef with omega 3 fatty acids.

PMID- 9648512
TI  - Docosahexaenoic acid-enriched milk.

PMID- 9648513
TI  - Omega 3 products: from research to retail.

PMID- 9648514
TI  - Utilization of omega 3 fatty acids in companion animal nutrition.

PMID- 9648515
TI  - Metabolism of alpha-linolenic acid from flaxseed in dogs.

PMID- 9648516
TI  - Global food fortification perspectives of long-chain omega 3 fatty acids.

PMID- 9648517
TI  - Regulatory aspects of omega 3 fatty acid labelling in Canada.

PMID- 9648518
TI  - Omega 3 fatty acids--an Australian perspective.

PMID- 9648519
TI  - Redefining dietary reference values and food safety.

PMID- 9648520
TI  - The cytotoxicity of 2-formyl and 2-acetyl-(6-picolyl)-4N-substituted
      thiosemicarbazones and their copper(II) complexes.
AB  - 2-Acetyl-(6-picolyl)-4N-substituted thiosemicarbazones and their copper(II)
      complexes were shown to be potent antineoplastic and cytotoxic agents against
      murine and human cultured cells. Numerous derivatives were as active against
      solid tumor growth as clinically useful agents. The agents inhibited L1210 DNA
      and RNA syntheses with inhibition of key regulatory enzyme activities of the
      purine pathway as well as nucleoside kinase activities. d[NTP] pools were reduced
      and DNA strand scission occurred. These agents were DNA topoisomerase II
      inhibitors with lower IC50 values than that of VP-16. However, they did not cause
      L1210 DNA protein linked breaks and actually protected against those breaks
      afforded by VP-16. The agents were not synergistic with VP-16 in reducing cell
      growth or DNA synthesis although they did reduce growth of L1210 cells in agar
      suspended media.

PMID- 9648521
TI  - Controlled insulin release from chitosan microparticles.
AB  - This study deals with the production of chitosan microparticles containing
      insulin by interfacial crosslinkage of chitosan solubilized in the aqueous phase
      of a water/oil dispersion in the presence of ascorbyl palmitate. The use of
      ascorbyl palmitate as interfacial crosslinker is based on its amphiphilic
      properties allowing its disposition at the water/oil interface of the preparative
      dispersion, thus permitting covalent bond formation with the amino groups of
      chitosan when its oxidation to dehydroascorbyl palmitate takes place during
      microparticle preparation. This preparation method produced microparticles
      characterized by high loading levels of insulin, completely releasing the drug in
      about 80 h at an almost constant release rate as determined by spectrophotometric
      and spectrofluorimetric methods. In contrast, the replacement of ascorbyl
      palmitate by dehydroascorbyl palmitate provided microparticles incompletely
      releasing the incorporated drug and characterized by a non-constant release rate
      over time due to the higher lipophilicity of dehydroascorbyl palmitate which
      hinders its disposition at the water/oil interface and thus decreases the
      crosslinking efficiency and increases the lipophilicity of the microparticle
      surface. The efficiency of the spectrofluorimetric and spectrophotometric methods
      used for determination of the stability and release of the insulin from the
      chitosan microparticles is also discussed.

PMID- 9648522
TI  - Synthesis and antibacterial activities of new carbapenems having a proline
      reverse amide moiety at the C-2 position.
AB  - The synthesis of new 1 beta-methylcarbapenems (1a-l) having a proline reverse
      amide moiety at the C-2 position and their in vitro antibacterial activities are
      described. The compounds were evaluated by the Mueller-Hinton agar dilution
      method and compared with meropenem as control. Aliphatic amides (1a-h) are found
      to show greater antibacterial activity than aromatic amides (1i-l). Moreover, C-2
      free amino compound (1m) reveals greater activity than any other amide compounds
      (1a-l).

PMID- 9648523
TI  - 7-Aminocoumarins are substrates of cytochrome P450-isozymes.
AB  - N-Alkyl-7-aminocoumarins are dealkylated by murine cytochrome P450. There are
      differences between the N-dealkylation of secondary and tertiary amines. 7
      Ethylamino-4-methylcoumarin is deethylated by isozymes induced by 3
      methylcholanthrene, in contrast to 7-diethylamino-4-methylcoumarin and 7-diethyl
      amino-4-trifluoromethylcoumarin, which are deethylated mostly by isozymes induced
      by phenobarbital. Although the deethylation of the secondary amine can be
      increased also by a pretreatment with pyrazole, a specific inducer of the
      coumarin 7-hydroxylase (CYP2A5), there is no specific affinity for this isozyme.
      This result is supported by the second specific inducer of CYP2A5 cobalt, because
      cobalt did not influence the deethylation of 7-ethylamino-4-methylcoumarin. In
      addition, it was shown that (in contrast to earlier investigations) pyrazole
      beside CYP2A5 also induces further cytochrome P450 isozymes. In series of four
      compounds, 7-ethylamino-4-methylcoumarin is the singular 7-aminocoumarin which is
      accepted as substrate by the coumarin 7-hydroxylase. In addition, the metabolism
      of the 7-aminocoumarins was investigated to look for further metabolic products.
      The most interesting result is the double deethylation of 7-diethylamino-4
      methylcoumarin to the primary amine. In the scope of the studies the advantages
      of new calculating structure-activity-relationships (QSAR-plot) could also be
      demonstrated.

PMID- 9648524
TI  - More than suggestion: the effect of interviewing techniques from the McMartin
      Preschool case.
AB  - Child interviewing techniques derived from transcripts of the McMartin Preschool
      case were found to be substantially more effective than simple suggestive
      questions at inducing preschool children to make false allegations against a
      classroom visitor. Thirty-six children interviewed with McMartin techniques made
      58% accusations, compared with 17% for 30 children interviewed with suggestive
      questions. Social influence and reinforcement appeared to be more powerful
      determinants of children's answers than simple suggestive questions. The SIRR
      model is proposed to explain how false statements may be elicited from children
      or adults. Categories identified in the SIRR model are suggestive questions,
      social influence, reinforcement, and removal from direct experience.

PMID- 9648525
TI  - Understanding pretest and posttest reactions to cognitive ability and personality
      tests.
AB  - To understand the nature of test reactions and their relationship to test
      performance, the relationships among belief in tests, pretest reactions, test
      performance, and posttest reactions were modeled for cognitive ability and
      personality tests. Results from structural equation models that were fitted to
      responses from 197 undergraduate examinees supported the hypothesized
      relationships. On the cognitive ability test, pretest reactions affected test
      performance and mediated the relationship between belief in tests and test
      performance. Test performance affected posttest reactions even after taking into
      account the effect of pretest reactions. On the personality test, belief in tests
      affected pretest and posttest reactions, but the three variables were unrelated
      to test performance (Conscientiousness scores). Conceptual, methodological, and
      practical implications of the findings are discussed in the context of research
      on test reactions and test performance.

PMID- 9648526
TI  - Emotional exhaustion as a predictor of job performance and voluntary turnover.
AB  - Recent research suggests that a better understanding of emotional exhaustion
      requires the development of new theoretical perspectives. To that end, with the
      conservation of resources model (COR) as the theoretical framework, the present 1
      year longitudinal study was undertaken. Composed of 52 social welfare workers,
      this research examined the relationship of emotional exhaustion to job
      satisfaction, voluntary turnover, and job performance. Positive affectivity (PA)
      and negative affectivity (NA) were used as control variables. Whereas emotional
      exhaustion was unrelated to job satisfaction, it was associated with both
      performance and subsequent turnover. In addition, the relationship between
      emotional exhaustion and performance and also between emotional exhaustion and
      turnover remained significant above and beyond the effects of PA and NA. Future
      research directions and implications of the findings are introduced.

PMID- 9648527
TI  - Singlet oxygen- versus nonsinglet oxygen-mediated mechanisms of sensitizer
      photobleaching and their effects on photodynamic dosimetry.
AB  - We report the effects of singlet oxygen (1O2) and non-1O2-mediated sensitizer
      photobleaching on oxygen consumption and dosimetry during photodynamic therapy
      (PDT) of sensitized multicell tumor spheroids. We develop a theoretical model for
      the description of non-1O2-mediated photobleaching resulting from irreversible
      reactions of the excited singlet or triplet sensitizer populations with cell
      substrate. We show that the fluence-dependent simple exponential decay expression
      of sensitizer degradation is not consistent with these mechanisms and, therefore,
      with any reasonable mechanism that we consider, because we have shown previously
      that 1O2-mediated photobleaching cannot be described by a simple exponential with
      a constant photobleaching coefficient (I. Georgakoudi et al., Photochem.
      Photobiol. 65, 135-144, 1997). Analysis of oxygen microelectrode measurements
      performed at the edge of Nile blue selenium (EtNBSe)- and protoporphyrin IX
      (PpIX)-sensitized spheroids during PDT demonstrates that the former drug
      photobleaches via a non-1O2-mediated mechanism, while the latter is degraded via
      a 1O2-mediated mechanism. Comparisons of the cytotoxic effects of EtNBSe with
      those of Photofrin (a drug that is degraded via a 1O2-mediated mechanism)
      indicate that the lower threshold 1O2 dose and the higher extinction coefficient
      and 1O2 yield for EtNBSe do not necessarily result in improved photodynamic
      effects, thus emphasizing the importance of the sensitizer photobleaching
      mechanism for dosimetry.

PMID- 9648528
TI  - Novel visible and ultraviolet light photogeneration of hydroxyl radicals by 2
      methyl-4-nitro-quinoline-N-oxide (MNO) and 4,4'-dinitro-(2,2')bipyridinyl-N,N'
      dioxide (DBD).
AB  - Chemicals that upon absorption of light generate hydroxyl radicals (.OH), free of
      other damaging species under physiological conditions, are useful tools for the
      study of the biological effects of .OH radical and for its utilization for
      analytical purposes. We report the novel property of 2-methyl-4-nitro-quinoline-N
      oxide (MNO) and 4,4'-dinitro-(2,2')bipyridinyl-N,N'-dioxide (DBD) to act as
      photogenerators of .OH with UV and visible light. Upon irradiation with 360-400
      nm light MNO and DBD generate free radicals that convert coumarin carboxylic acid
      (CCA) to fluorescent 7-OH-CCA; the .OH radical scavengers dimethylsulfoxide
      (DMSO) and ethanol eliminate the induction of 7-OH-CCA fluorescence. Upon 400 nm
      illumination in the presence of MNO, supercoiled plasmid DNA is converted to
      circular and strand breakage is significantly reduced in the presence of DMSO and
      completely absent in the absence of MNO. The conversion of CCA to 7-OH-CCA and of
      supercoiled plasmid to circular DNA are also observed in the absence of oxygen.
      Taken together, these data indicate that MNO and DBD constitute novel .OH
      generating compounds. Because currently known .OH-photogenerating compounds
      require UV illumination (< 360 nm) that also damages DNA and cells directly, the
      property of MNO to generate .OH upon 400 nm illumination is advantageous when
      studies on cells, DNA and other biomolecules are conducted.

PMID- 9648529
TI  - Fluorescence anisotropy controlled by light quenching.
AB  - We demonstrated that fluorescence anisotropy can be effectively decreased or
      increased in the presence of light quenching, depending on relative polarizations
      of excitation and quenching pulses. For parallel light quenching, anisotropy
      decreases to 0.103 and z-axis symmetry is preserved. In the presence of
      perpendicular light quenching, the steady-state anisotropy of a pyridine-2
      glycerol solution increases from 0.368 for an unquenched sample to 0.484 for a
      quenched one. We show that the angular distribution of transition moments loses z
      axis symmetry in the presence of perpendicular light quenching. In these cases we
      used more general definitions of anisotropy. Induced by light quenching,
      anisotropy can be applied in both steady-state and time-resolved measurements. In
      particular, the systems with low or no anisotropy can be investigated with the
      proposed technique.

PMID- 9648530
TI  - Assessment of DNA damage induced by broadband and narrowband UVB in cultured
      lymphoblasts and keratinocytes using the comet assay.
AB  - Phototherapy with broadband UVB is an effective treatment for inflammatory
      dermatoses. A newly developed fluorescent UVB lamp (Philips TL01) that emits a
      narrowband UVB around 311 nm was shown to be superior for the phototherapy of
      psoriasis. In order to contribute to the knowledge about the carcinogenic
      potential of this UVB source, we measured the DNA damage in lymphoblasts and
      keratinocytes induced by narrowband UVB and compared it with that by conventional
      broadband UVB using the single cell gel electrophoresis (comet assay). At equal
      doses, broadband UVB produced more DNA damage than narrowband UVB. However, in
      phototherapy of psoriasis, up to 10-fold higher doses are used with TL01. When
      therapeutically equivalent doses were compared (10-fold correction for narrowband
      UVB), we found only slight differences in the amount of DNA damage produced by
      broadband and narrowband UVB. This supports the already existing evidence that
      for phototherapy narrowband UVB is not more carcinogenic than broadband UVB.

PMID- 9648531
TI  - Protection against UV-induced reactive intermediates in human cells and mouse
      skin by glutathione precursors: a comparison of N-acetylcysteine and glutathione
      ethylester.
AB  - Because glutathione (GSH) plays a central part in the endogenous defense against
      UV radiation, an increase in GSH might provide photoprotection. Two agents that
      increase GSH levels were investigated. Cultured human cells and mouse skin were
      treated with N-acetylcysteine (NAC) and glutathione ethylester (GSH-Et). After 30
      min, the GSH level was determined by HPLC. Photoprotection was assessed by
      testing the ability of the thiols to scavenge UV-induced reactive intermediates
      in the same models. As compared to control cells, NAC and GSH-Et increased
      intracellular GSH in vitro to maximally 144% and 174% respectively. In vitro
      protection (maximum 23% for NAC and 21% for GSH-Et) did not correlate to the
      intracellular GSH level but to the concentration of the thiols in the medium. In
      vivo, epidermal GSH was increased to maximally 163% of the control level by NAC
      and 1234% by GSH-Et. The maximum in vivo photoprotection provided by GSH-Et was
      55%, similar to what was found previously for NAC. Again, the protection seemed
      more closely correlated to the thiol dose than to the GSH level. The study showed
      that the protection against UV-induced reactive intermediates depends on a
      general antioxidant action of these thiols, rather than only on their role as GSH
      precursors.

PMID- 9648532
TI  - Inhibitory effects of plant tannins on ultraviolet light-induced epidermal DNA
      synthesis in hairless mice.
AB  - Naturally occurring hydrolyzable (HT) and condensed (CT) tannins and their
      monomeric units were tested for their ability to inhibit the stimulation of DNA
      synthesis by UVB radiation. Hairless mice were irradiated with either single (200
      mJ/cm2) or multiple (150 mJ/cm2) doses of UVB applied at 24 h intervals and
      epidermal DNA synthesis was measured at different times after the last of these
      treatments. The peak of DNA synthesis that is observed 48-56 h after a single UVB
      irradiation shifts to an earlier time of 16-24 h after multiple UVB treatments.
      Interestingly, the early inhibitory period of DNA synthesis observed 8 h after a
      single UVB treatment is not detected following multiple UVB treatments. Rather,
      DNA synthesis is stimulated six-fold 24 h after multiple UVB treatment, a
      response that is higher than the peak occurring 48-56 h after a single UVB
      irradiation. The disappearance of the early period of inhibition when the peak of
      DNA synthesis shifts to an earlier time may be linked to reactive oxygen species
      brought to the epidermis by infiltrating leukocytes, which, in turn, act as
      second messengers to stimulate growth signals in cells. Topical applications of
      HT or CT remarkably inhibit the DNA responses to single and multiple UVB
      treatments, an effect that is dependent on the dose and time of administration.
      Indeed, the peak stimulation of DNA synthesis is maximally inhibited when 17 mg
      of Tarapod tannic acid (TA), an HT, are applied topically 20 min before a single
      UVB treatment. The polymeric tannins inhibited DNA synthesis to a greater degree
      than equal doses of their monomeric units, gallic acid and catechin. These
      results suggest that various oligomeric HT and CT may be useful against tumor
      promoting responses associated with the exposure of skin to physical carcinogens.

PMID- 9648533
TI  - Postadministration protective effect of magnesium-L-ascorbyl-phosphate on the
      development of UVB-induced cutaneous damage in mice.
AB  - The effects of stable vitamin C, magnesium-L-ascorbyl-2-phosphate (MAP),
      administered after acute and chronic exposure to UVB irradiation were
      investigated using hairless mice. Intraperitoneal administration of 100 mg/kg of
      MAP immediately after acute exposure to 15 kJ/m2 of UVB significantly prevented
      increases of UVB-induced lipid peroxidation in skin and sialic acid in serum, an
      inflammation marker. Administration of 50 mg/kg of MAP immediately after each
      exposure significantly delayed skin tumor formation and hyperplasia induced by
      chronic exposure to 2 kJ/m2 of UVB. Intraperitoneal administration of 200 mg/kg
      of MAP produced an increase in ascorbic acid (As) levels in the serum, liver and
      skin within 15 min. Serum As levels quickly returned to normal, but hepatic and
      cutaneous levels remained elevated before returning to normal after 24 h,
      suggesting that MAP was converted to As in the serum and in those tissues.
      Ultraviolet B-induced hydroxyl radical generation in murine skin homogenates was
      scavenged by As-Na addition, which was directly detected by electron spin
      resonance (ESR). These results suggest that postadministration of MAP delays
      progression of skin damage induced by UVB irradiation. It is presumed that MAP,
      once converted to As, exhibits such inhibitory effects by scavenging hydroxyl and
      lipid radicals generated as a direct or indirect result of UVB exposure.

PMID- 9648534
TI  - The general kinetic model of electron transfer in photosynthetic reaction centers
      activated by multiple flashes.
AB  - A new general kinetic model for the functioning of photosynthetic reaction
      centers (RC) of purple bacteria, under multiple flash activation, has been
      developed. The model includes the primary electron donor (P870) as well as the
      primary (QA) and secondary (QB) acceptor quinones. The new features of this
      general model include: (1) consideration of four different states of the QB
      binding site (vacant, occupied by QB, by QB- and by QBH2), (2) incorporation of
      the dark relaxation of the RC between flashes, (3) the assumption of fast
      exchange of quinones between the RC and quinone pool in detergent micelles or
      chromatophore membrane, (4) description of the kinetics of electron transfer in
      both oxidized (no donor for P870+) and reduced (in the presence of donor for
      P870+) conditions simultaneously, (5) the consideration of both single and
      multiple flash activation of the RC of purple bacteria and (6) consideration of
      the cumulative effects of all previous flashes of the series in the response
      induced by the current flash. This model is used to calculate and predict (1)
      flash-induced binary oscillations of the secondary acceptor semiquinone (QB-),
      (2) flash-induced behavior of P870+ in the presence and absence of electron donor
      and (3) the apparent equilibrium constant of electron transfer between QA and QB
      and others. Different characteristics of RC are analyzed as a function of flash
      intensity, time between flashes, concentration of electron donor, redox-potential
      of the medium, concentration of pool quinone and quinol, association and
      dissociation equilibrium constants for quinone and quinol at the QB binding site,
      equilibrium constants of electron transfer between QA- and QB and between QA- and
      QB-, as well as the rate constants of oxidation of QA- and QB- by redox
      mediators. The proposed model can be used as a basis for assays of kinetic
      behavior of native and mutant RC of purple bacteria and for determination of the
      factors influencing the release of QH2 from RC. The latter is needed for analysis
      of factors controlling light-activated electron transport in the cytochrome bc1
      complexes of purple bacteria by quinol molecules released from RC. The developed
      general approach for parallel consideration of flash-induced transitions of RC
      and its following dark relaxation between flashes can also be used for kinetic
      description of photosynthetic RC of oxygenic photosynthesis.

PMID- 9648535
TI  - Duck hepatitis B virus inactivation and 8-methoxypsoralen photoadduct formation
      in human platelet concentrates.
AB  - Photochemical inactivation (PCI) of virus and bacteria in platelet concentrates
      (PC) has been demonstrated using 8-methoxypsoralen (8-MOP) and long-wavelength UV
      light (UVA). To study inactivation of blood-borne virus, we have employed duck
      hepatitis B virus (DHBV), a model for human hepatitis B virus. A specific
      hepatocyte culture infectivity assay, with PCR detection, could measure 5-6 log10
      virus kill. The DHBV inactivation in PC was dependent on UVA dose, was enhanced
      when plasma was reduced from 100% to 20% and was limited by 8-MOP solubility in
      the reduced-plasma medium. Optimum conditions for PCI were 100 micrograms/mL 8
      MOP in 20% plasma and 80% synthetic platelet storage medium. A radiolabeling
      assay for 8-MOP photoadducts in hepatocytes seeded into PC confirmed that DHBV
      inactivation reflected DNA modification and indicated that adduct formation was
      insensitive to minor variations in conditions. Kinetic modeling indicated that
      optimum adduct formation was a compromise between 8-MOP dark binding and optical
      transmittance and that plasma proteins competed for 8-MOP binding. The PCI
      results in various media correlated with corresponding DNA modification densities
      and were compared to statistical models incorporating DHBV characteristics and
      predictions of 8-MOP crosslink formation between DNA strands. Behavior was
      consistent with one or a small number of lethal modifications per DNA strand,
      including monoadducts, but probably not crosslinks alone. A minor subpopulation
      of DHBV was found to be somewhat more difficult to inactivate, consistent with
      three-fold lower modification, due possibly to single-stranded DNA character or
      host repair of photoadducts.

PMID- 9648536
TI  - Susceptibility to effects of UVB irradiation on induction of contact sensitivity,
      relevance of number and function of Langerhans cells and epidermal macrophages.
AB  - Sensitization on skin exposed to acute low-dose UVB irradiation separates normal
      humans into two phenotypically distinct groups: One group, following
      sensitization on UVB-irradiated skin, develops contact sensitivity, designated
      UVB resistant (UVB-R) and the second group, following sensitization on UVB
      irradiated skin, fails to develop contact sensitivity, designated UVB susceptible
      (UVB-S). To investigate whether UVB susceptibility in humans in related to
      antigen-presenting activity in the skin we studied the effect of UVB irradiation
      on the number and function of the epidermal antigen-presenting cells in
      volunteers identified as UVB-R and UVB-S. Single cell suspensions of epidermal
      cells from control skin and skin exposed to 3 minimal erythema doses (MED) of UVB
      3 days previously were stained for Langerhans cells (CD1a+HLA-DR+) and epidermal
      macrophages (CD1a-HLA-DR+). The UVB exposure of the skin significantly decreased
      the percentage of Langerhans cells (UVB-R: n = 7, P < 0.02, UVB-S: n = 6, P <
      0.03) and increased the percentage of epidermal macrophages (UVB-R: n = 7, P <
      0.03, UVB-S: n = 6, P < 0.03) however to the same degree in both the UVB-R and
      the UVB-S group. To study the effect on Langerhans cell alloreactivity, epidermal
      cells were harvested immediately after UVB irradiation. However, in both UVB-R
      and UVB-S subjects the Langerhans cell alloreactivity was blocked to the same
      degree immediately after UVB irradiation compared to nonirradiated epidermal
      cells. To determine the effect of UVB irradiation on epidermal macrophages,
      epidermal cells were harvested 3 days after UVB irradiation. Irradiated epidermal
      cells from both UVB-R and UVB-S subjects demonstrated a strong antigen-presenting
      capacity compared to epidermal cells from control skin leading to activation of T
      cells that mainly secrete interferon (IFN)-gamma and not interleukin (IL)-4. In
      conclusion we found that UVB susceptibility was not correlated with the number of
      Langerhans cells or epidermal macrophages in the skin at the same time of
      sensitization. Neither was it correlated with the capacity of Langerhans cells
      nor UVB-induced epidermal macrophages to activate T cells in vitro.

PMID- 9648537
TI  - Variation in photodynamic efficacy during the cellular uptake of two
      phthalocyanine photosensitizers.
AB  - A decrease in the efficacy of photodynamic therapy (PDT) with phthalocyanine
      photosensitizers was observed for lymphoblastic murine and human cell lines as
      the time between the addition of the photosensitizer, aluminum phthalocyanine
      (AIPc), to the culture medium and exposure to light was increased from 4 h to 18
      h. The total intracellular concentration of photosensitizer did not decrease
      significantly during this 18 h interval. For the murine cell lines, the maximum
      cytotoxic and mutagenic effects were observed when the time between addition of
      the photosensitizer and irradiation was between 1 and 4 h. The time course of the
      variations in efficacy did not vary greatly from one murine cell line to another,
      even though the cell lines differ markedly in the extent of their cytotoxic and
      mutagenic response. The time course of the variation was similar for cytotoxicity
      and mutagenicity, as well as for the induction of DNA fragmentation. The human
      lymphoblastic cell line, WTK1, showed less variation in survival and mutability
      with time than did the murine cell lines. With Pc 4
      (HOSiPcOSi[CH3]2[CH2]3N[CH3]2) as the photosensitizer, the photocytotoxicity for
      murine L5178Y (LY)-S1 cells did not change significantly as the time between
      addition of Pc 4 and irradiation was increased from 2 to 18 h. However, the
      mutagenicity decreased by a factor of three during this interval. The
      mutagenicity of PDT with Pc 4 was much less in LY-S1 cells than that with AlPc.
      The results suggest that the variation in the efficacy observed for AlPc-induced
      photocytotoxicity is caused by changes in the intracellular distribution and/or
      the aggregation of the photosensitizer with time after its addition.

PMID- 9648538
TI  - Effect of membrane potential on the binding of merocyanine 540 to human
      erythrocytes.
AB  - Illumination of erythrocytes in the presence of merocyanine 540 (MC540) resulted
      in changed binding characteristics of MC540, i.e. a red shift in the emission
      maximum of bound dye with an increase in the relative fluorescence quantum yield.
      Aluminum phthalocyanine tetrasulfonate-mediated photodynamic treatment, before
      addition of MC540, resulted in a comparable change in the MC540-binding
      characteristics with, in addition, an increase in the concentration of MC540 in
      the membrane. Both photodynamic treatments induce depolarization of the red cell
      membrane, with a dose dependency comparable to that of changed MC540 binding.
      Also depolarization, induced by incubation of the cells with A23187 in the
      presence of Ca2+ in high [K+] buffer, resulted in similar changes in the MC540
      binding characteristics. These results indicate a relation between
      photodynamically induced membrane depolarization and changed MC540-binding
      characteristics. Hyperpolarization induced by incubation with A23187 in low [K+]
      buffer resulted in decreased binding of MC540. In accordance, the MC540-mediated
      photodamage to red cells decreased upon hyperpolarization of the cells. The
      results indicate that the binding of MC540 to erythrocytes is strongly dependent
      on the membrane potential and that hyperpolarization of the membrane could be a
      possible protection mechanism for erythrocytes against MC540-mediated
      photodynamic damage.

PMID- 9648539
TI  - Literally changing the brain.

PMID- 9648540
TI  - From sensation to cognition.
AB  - Sensory information undergoes extensive associative elaboration and attentional
      modulation as it becomes incorporated into the texture of cognition. This process
      occurs along a core synaptic hierarchy which includes the primary sensory,
      upstream unimodal, downstream unimodal, heteromodal, paralimbic and limbic zones
      of the cerebral cortex. Connections from one zone to another are reciprocal and
      allow higher synaptic levels to exert a feedback (top-down) influence upon
      earlier levels of processing. Each cortical area provides a nexus for the
      convergence of afferents and divergence of efferents. The resultant synaptic
      organization supports parallel as well as serial processing, and allows each
      sensory event to initiate multiple cognitive and behavioural outcomes. Upstream
      sectors of unimodal association areas encode basic features of sensation such as
      colour, motion, form and pitch. More complex contents of sensory experience such
      as objects, faces, word-forms, spatial locations and sound sequences become
      encoded within downstream sectors of unimodal areas by groups of coarsely tuned
      neurons. The highest synaptic levels of sensory-fugal processing are occupied by
      heteromodal, paralimbic and limbic cortices, collectively known as transmodal
      areas. The unique role of these areas is to bind multiple unimodal and other
      transmodal areas into distributed but integrated multimodal representations.
      Transmodal areas in the midtemporal cortex, Wernicke's area, the hippocampal
      entorhinal complex and the posterior parietal cortex provide critical gateways
      for transforming perception into recognition, word-forms into meaning, scenes and
      events into experiences, and spatial locations into targets for exploration. All
      cognitive processes arise from analogous associative transformations of similar
      sets of sensory inputs. The differences in the resultant cognitive operation are
      determined by the anatomical and physiological properties of the transmodal node
      that acts as the critical gateway for the dominant transformation. Interconnected
      sets of transmodal nodes provide anatomical and computational epicentres for
      large-scale neurocognitive networks. In keeping with the principles of
      selectively distributed processing, each epicentre of a large-scale network
      displays a relative specialization for a specific behavioural component of its
      principal neurospychological domain. The destruction of transmodal epicentres
      causes global impairments such as multimodal anomia, neglect and amnesia, whereas
      their selective disconnection from relevant unimodal areas elicits modality
      specific impairments such as prosopagnosia, pure word blindness and category
      specific anomias. The human brain contains at least five anatomically distinct
      networks. The network for spatial awareness is based on transmodal epicentres in
      the posterior parietal cortex and the frontal eye fields; the language network on
      epicentres in Wernicke's and Broca's areas; the explicit memory/emotion network
      on epicentres in the hippocampal-entorhinal complex and the amygdala; the face
      object recognition network on epicentres in the midtemporal and temporopolar
      cortices; and the working memory-executive function network on epicentres in the
      lateral prefrontal cortex and perhaps the posterior parietal cortex. Individual
      sensory modalities give rise to streams of processing directed to transmodal
      nodes belonging to each of these networks. The fidelity of sensory channels is
      actively protected through approximately four synaptic levels of sensory-fugal
      processing. The modality-specific cortices at these four synaptic levels encode
      the most veridical representations of experience. Attentional, motivational and
      emotional modulations, including those related to working memory, novelty-seeking
      and mental imagery, become increasingly more pronounced within downstream
      components of unimodal areas, where they help to create a highly edited
      subjective version of the world. (ABSTRACT TRUNCATED)

PMID- 9648541
TI  - The illiterate brain. Learning to read and write during childhood influences the
      functional organization of the adult brain.
AB  - Learning a specific skill during childhood may partly determine the functional
      organization of the adult brain. This hypothesis led us to study oral language
      processing in illiterate subjects who, for social reasons, had never entered
      school and had no knowledge of reading or writing. In a brain activation study
      using PET and statistical parametric mapping, we compared word and pseudoword
      repetition in literate and illiterate subjects. Our study confirms behavioural
      evidence of different phonological processing in illiterate subjects. During
      repetition of real words, the two groups performed similarly and activated
      similar areas of the brain. In contrast, illiterate subjects had more difficulty
      repeating pseudowords correctly and did not activate the same neural structures
      as literates. These results are consistent with the hypothesis that learning the
      written form of language (orthography) interacts with the function of oral
      language. Our results indicate that learning to read and write during childhood
      influences the functional organization of the adult human brain.

PMID- 9648542
TI  - Learning from the pupil: a spatial visual channel in the absence of V1 in monkey
      and human.
AB  - The pupil of the normal human subject constricts in response not only to average
      increases in light energy, but also selectively to the spatial structure of a
      visual stimulus even when there are no energy changes. This enables one to
      measure visual acuity and sensitivity as a function of spatial frequency. It is
      known that pupillometric measures of acuity correlate well with those determined
      psychophysically for normal human observers. The purpose of the present study was
      to measure pupillary changes with stimuli delivered to the 'blind' hemifields of
      monkeys with unilateral V1 removal, and also with stimulation of a human subject
      (G.Y.) with putative V1 destruction. The results show that there are small but
      reliable pupillary changes to flux-equated gratings in the blind fields both in
      monkeys and human. The response profile in both species is very similar: it is
      narrowly tuned, with a peak at approximately 1 cycle/degree and a cut-off acuity
      of approximately 7 or 8 cycles/degree, a significant reduction compared with the
      intact hemifield. The result also maps well onto the psychophysically determined
      spatiotemporal response profile to gratings in the blind field, as determined
      independently for G.Y. Thus, there is a narrowly tuned spatial visual channel
      that does not require the integrity of V1 in monkey or human. There was no
      evidence under these particular conditions in either monkeys or subject G.Y. of a
      pupillary response to an equiluminant change from white to green or red in the
      hemianopic field. The pupil holds promise as a non-verbal, indirect method for
      determining the spatial profile, sensitivity and other properties of residual
      visual capacity, both in animals and humans.

PMID- 9648543
TI  - Spontaneous sharp waves in human neocortical slices excised from epileptic
      patients.
AB  - Human neocortical temporal lobe tissue resected for treatment of
      pharmacoresistant epilepsy was investigated. In slices prepared from this tissue,
      field potentials sometimes superimposed by population spikes were found to appear
      spontaneously. In individual slices, they were generalized or highly localized to
      a field of approximately 200 microns in diameter. Synchronous with these
      potentials, hyperpolarizing and depolarizing postsynaptic potentials were
      recorded from neurons in the vicinity of the field potential electrode.
      Hyperpolarizing postsynaptic potentials appeared to be mainly chloride mediated.
      All potentials, i.e. sharp field potentials as well as postsynaptic potentials,
      were reversibly suppressed by blockade of the non-NMDA (non-N-methyl-D-aspartate)
      glutamate-subreceptor and of the GABAA (gamma-aminobutyric acid) receptor, and by
      application of the organic calcium channel blocker verapamil. By contrast, all
      potentials remained unaffected by blockade of the NMDA glutamate-subreceptor and
      the GABAB receptor. The antiepileptic drugs carbamazepine and phenytoin failed to
      suppress the spontaneous potentials at therapeutic concentrations. Washout of
      Mg2+ from the superfusate left the spontaneous potentials unchanged or converted
      them to ictal-type discharges. This epileptiform activity was not suppressed, but
      augmented by blockade of the GABAA receptor. As a whole, the spontaneously
      appearing field potentials may be assumed to reflect a state of increased
      neuronal synchronization.

PMID- 9648544
TI  - Nitric oxide-induced oxidative stress in autosomal recessive and dominant
      inclusion-body myopathies.
AB  - Autosomal-recessive and autosomal-dominant hereditary inclusion-body myopathies
      are severe, progressive muscle diseases, characterized pathologically by
      vacuolated muscle fibres containing paired helical filaments. We immunostained
      muscle biopsy specimens from quadriceps-sparing autosomal-recessive and autosomal
      dominant inclusion-body myopathy subjects, disease-control subjects and normal
      patients, utilizing isoform-specific antibodies against the neuronal and
      inducible forms of nitric oxide synthase, and antibodies against nitrotyrosine.
      Approximately 75% of the vacuolated muscle fibres in all recessive and dominant
      inclusion-body myopathy patients contained inclusions strongly immunoreactive
      with antibodies against neuronal and inducible nitric oxide synthase which, by
      immunoelectron microscopy, were colocalized to clusters of tubulofilaments
      (previously shown, by us, to be paired helical filaments). Strong nitrotyrosine
      immunoreactivity was in the form of multiple dots and large granular patches,
      which ultrastructurally did not immunolocalize to tubulofilaments. Excess
      intracellular nitric oxide can combine with superoxide to produce highly toxic
      peroxynitrite, which can nitrate tyrosines of proteins. The presence of
      nitrotyrosine is indicative of nitric oxide-induced oxidative stress. Our data
      suggest that oxidative stress plays a role in the pathogenic cascade of
      hereditary inclusion-body myopathies.

PMID- 9648545
TI  - Corticobulbar tract involvement in amyotrophic lateral sclerosis. A transcranial
      magnetic stimulation study.
AB  - We investigated corticobulbar tract function by recording from the tongue and
      orofacial muscles and using transcranial magnetic stimulation (TMS) in 30
      patients with amyotrophic lateral sclerosis (ALS) in order to improve the
      diagnostic yield in the detection of subclinical upper motor neuron (UMN)
      dysfunction. A UMN lesion was assumed when the peripheral conduction time and
      amplitude of the M-wave were within normal range and either the response to
      cortical stimulation was absent, or the central conduction time was delayed (>
      mean + 2.5 SD). Only two patients showed clinical evidence of UMN involvement in
      the cranial nerves, while TMS demonstrated corticobulbar tract dysfunction in the
      orofacial muscles in 17 patients (57%) and to the tongue in 15 patients (50%).
      Following recording at both sites, corticobulbar tract dysfunction was confirmed
      in 21 patients (70%). Twelve out of 13 patients with bulbar symptoms had evidence
      of additional subclinical corticobulbar tract involvement using TMS. In seven out
      of 15 patients with isolated limb involvement, subclinical corticobulbar tract
      dysfunction was demonstrated. Our results indicate the presence of early and, in
      most cases, subclinical corticobulbar tract involvement in the pathways to the
      orofacial muscles and tongue in ALS.

PMID- 9648546
TI  - Central motor conduction time in progressive multiple sclerosis. Correlations
      with MRI and disease activity.
AB  - The purpose of this study was to relate abnormalities of motor conduction time to
      the presence of spinal cord MRI lesions in progressive multiple sclerosis and to
      investigate the relationship between changes in motor conduction over time and
      clinical and MRI changes. Central motor conduction time (CMCT), serial MRI of the
      brain and spinal cord, and clinical evaluations were carried out in 20 patients
      with primary and secondary progressive multiple sclerosis. CMCT was carried out
      at the beginning and end of the study whilst the clinical and MRI examinations
      occurred at monthly intervals for 12 months. Median CMCT to abductor pollicis
      brevis was 14.8 ms (range 8.8-27.4 ms). The response latency to tibialis anterior
      correlated with disability measured on the Expanded Disability Status Scale.
      Latencies to upper limb muscles correlated with cervical MRI lesion load and the
      presence of atrophy of the cervical cord. Over the 12-month study period, 15 of
      19 patients deteriorated clinically. However, an increase in motor response
      latencies occurred only in the four patients who had developed new cord lesions.
      The results suggest that prolonged CMCT is related to spinal cord lesion load and
      that, over time, changes in the CMCT occur only when spinal cord lesion load
      increases. Clinical change in progressive multiple sclerosis may therefore occur
      without either the development of new lesions on MRI scans or an increase in
      motor conduction time. This suggests that clinical deterioration in these
      patients may occur by a mechanism other than increasing demyelination. This may
      be progressive axonal degeneration.

PMID- 9648547
TI  - Ocular search during line bisection. The effects of hemi-neglect and hemianopia.
AB  - We examined ocular fixations during line bisection in five patients with left
      hemianopia, two patients with right hemianopia, nine patients with left hemi
      neglect and nine normal control subjects. Compared with measures in control
      subjects, the median fixation, and left- and rightmost fixations were shifted
      contralaterally in patients with hemianopia alone and ipsilaterally in patients
      with hemi-neglect. The fixation with the longest duration and the bisection point
      were also shifted contralaterally with hemianopia and ipsilaterally with hemi
      neglect. However, the number of fixations and the spatial range spanned by
      fixations did not differ between the groups, showing that ocular exploration was
      not truncated in any group. Only some patients showed a previously reported
      directional search bias. Overall, there was no directional bias in saccadic
      number or amplitude. The distribution of fixations was most dense at the centre
      of the line in normal subjects, while hemianopic patients fixated most frequently
      at the ends of lines in their contralateral (blind) hemispace and at a central
      locus that was biased slightly contralaterally, as was their bisection judgement.
      This contralateral bias may reflect either an adaptive contralateral attentional
      gradient or a non-veridical spatial representation within the remaining normal
      hemifield. Hemi-neglect patients had a broad distribution of fixation peaks in
      the ipsilateral hemispace. Of two hemi-neglect patients with many fixations, one
      clustered fixations at a position right of centre, as if a normal fixation
      pattern was shifted rightward, while the other had two fixation peaks: one to the
      far right and the other near the centre of the line, reminiscent of the dual
      peaks of activity seen in some recent hemi-neglect models. These data reveal a
      heterogeneity in the routes by which right-biased judgements of spatial centre
      are reached by hemi-neglect patients.

PMID- 9648548
TI  - Distinct time courses of word and context comprehension in the left temporal
      cortex.
AB  - The time course and cortical basis of reading comprehension were studied using
      magnetoencephalography. The cortical structures implicated most consistently with
      comprehension were located in the immediate vicinity of the left auditory cortex,
      where final words totally inappropriate to the overall sentence context evoked
      enduring activation starting approximately 250 ms and lasting up to 600 ms after
      word onset. Contextually appropriate but unexpected words produced weaker
      activation which terminated earlier. Highly anticipated words totally failed to
      activate this area, suggesting that the conceptual network became involved only
      if unexpected information was detected during the primary word identification
      process. We propose that the point in time (350 ms after word onset) where the
      response to appropriate but unexpected endings started to diverge from those to
      contextually inappropriate endings reflects the boundary between understanding a
      single word and the meaning of a whole sentence.

PMID- 9648549
TI  - Aversive gustatory stimulation activates limbic circuits in humans.
AB  - Animal studies implicate the amygdala and its connections in the recognition of
      aversive stimuli. A recent PET study demonstrated that the human amygdala and
      left orbitofrontal cortex show substantial increases in regional cerebral blood
      flow (rCBF) during exposure to aversive odourants. To examine if aversive
      gustatory stimuli similarly activate these regions, nine healthy women tasted an
      aversive saline solution, pure water and chocolate while rCBF was measured with
      PET. The aversive saline condition, when contrasted with the water condition,
      increased activity in the right amygdala, left anterior orbitofrontal cortex,
      medial thalamus, pregenual and dorsal anterior cingulate, and the right
      hippocampus. The right amygdala, left orbitofrontal cortex and pregenual
      cingulate remained significantly activated when saline was compared with
      chocolate. The present results indicate that the amygdala and orbitofrontal
      cortex respond to aversive stimuli in both the olfactory and gustatory
      modalities, and highlight the role of the pregenual cingulate in negative
      emotional processing.

PMID- 9648550
TI  - Differential effect of a dopaminergic agonist on prefrontal function in traumatic
      brain injury patients.
AB  - We examined the effects of low-dose bromocriptine, a D2 dopamine receptor
      agonist, on processes thought to be subserved by the prefrontal cortex, including
      working memory and executive function, in individuals with traumatic brain
      injury. A group of 24 subjects was tested using a double-blind, placebo
      controlled crossover trial, counterbalanced for order. Bromocriptine was found to
      improve performance on some tasks thought to be subserved by prefrontal function,
      but not others. Specifically, there was improvement in performance on clinical
      measures of executive function and in dual-task performance, but not measures
      that tap the ability to maintain information in working memory without
      significant executive demands. Also, on control tasks not thought to be dependent
      on the prefrontal cortex, no improvement on bromocriptine was noted. These
      results demonstrate a selective effect of bromocriptine on cognitive processes
      which involve executive control, and provide a foundation for potential therapies
      for patients with prefrontal damage causing dysexecutive syndromes.

PMID- 9648551
TI  - Ocular tracking of step-ramp targets by patients with unilateral cerebral
      lesions.
AB  - The relationship of sinusoidal smooth pursuit defects to pursuit defects with
      step-ramp targets in patients with cerebral lesions is unclear. We examined
      pursuit and saccades to both step-ramp and sinusoidal targets in 17 patients with
      unilateral cerebral lesions. Two types of pursuit defects were found. One group
      of three patients had ipsi-directional sinusoidal pursuit defects from lesions to
      the posterior internal capsule. Their chief abnormality with step-ramp targets
      was increased contra-directional pursuit. Their ipsi-directional step-ramp
      pursuit was often normal and disproportionately better than their ipsi
      directional sinusoidal pursuit. Another patient with a parietal lesion had a
      second type of pursuit defect. He had low-normal sinusoidal pursuit bilaterally,
      but decreased ipsi- and contra-directional step-ramp pursuit. Also, he had an
      abnormal contra-directional drift after saccades to stationary targets. Despite
      these pursuit defects, saccadic accuracy did not show poor compensation for
      target motion in either patient type. The patient with the parietal lesion also
      had increased latencies for contralateral saccades. Recovery of pursuit was
      studied in one patient with an infarct of the posterior internal capsule.
      Initially he had a contra-directional bias that caused decreased ipsi-directional
      pursuit, increased contra-directional pursuit, and a contra-directional drift
      after saccades to stationary targets. Four months later, ipsi-directional pursuit
      and the post-saccadic drift to stationary targets had recovered, but contra
      directional pursuit remained abnormally high. We conclude that lesions of
      descending pursuit tracts in the internal capsule are characterized by a contra
      directional bias which recovers partly through a direction-specific adaptation.
      Lesions that affect the human homologue of posterior parietal cortex cause
      asymmetric bi-directional defects in pursuit initiation and increased
      contralateral saccadic latencies.

PMID- 9648552
TI  - Molecular genetics of renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) is an important clinical problem for which an
      effective treatment has yet to be developed. Importantly, the 5-year survival is
      below 50%. A better understanding of the underlying biological mechanisms could
      result in improvements in the prevention and treatment of this disease. The
      molecular mapping of chromosomal losses in renal cell cancer together with
      increased resolution of the human gene map will provide targets for therapeutic
      approaches. In this review, I summarize what is known regarding some tumor
      suppressor genes and candidate tumor suppressor genes in RCC, with reference to
      their location and expression.

PMID- 9648553
TI  - A recurrent nonrandom translocation (3;7)(q27;p12) associated with BCL-6 gene
      rearrangement in B-cell diffuse large cell lymphoma.
AB  - Two cases of B-cell diffuse large cell lymphoma associated with the
      t(3;7)(q27;p12) and BCL-6 rearrangement are described. Cytogenetic studies
      revealed [case 1] 47,XY,t(3;7)(q27;p12),+12 and [case 2] 45,X,
      Y,t(3;7)(q27;p12),del(6)(q21q25),+16,-21. The translocation of each case had a
      non-random chromosomal change involving a 3q27 locus associated with BCL-6 gene
      rearrangement identified by Southern blot analysis. Both cases involved multiple
      lymph nodes and extranodal regions, such as stomach and peritoneal cavity in case
      1, extranodal retroperitoneal space, subcutis, probable liver, and colon in case
      2. Chemotherapy provided only short survival after onset: 17 and 16 months,
      respectively. Altered expression of adhesion molecules CD44, CD54 (case 1) and
      CD11a and CD18 (case 2) may help to explain the poor outcome of these patients.

PMID- 9648554
TI  - Translocation (10;11)(p13;q13) and MLL gene rearrangement in a case of AML (M5a)
      with aggressive leukemia cutis.
AB  - A male patient with a secondary acute monocytic leukemia whose leukemia cells had
      a t(10;11)(p13;q13) chromosomal abnormality is described. Gene analysis disclosed
      that the patient's leukemia cells had MLL gene rearrangement. His leukemia cells
      responded poorly to chemotherapy, and the patient developed an unusual aggressive
      leukemia cutis. A t(10;11)(p13;q13) chromosomal abnormality that expresses MLL
      gene rearrangement has not been reported previously in secondary leukemia.

PMID- 9648555
TI  - Genetic alterations in colorectal cancer, comparative analysis of deletion
      events, and point mutations.
AB  - Although data on genetic alterations leading to the development of colorectal
      cancer are abundant, no specific genetic alteration, as has been demonstrated for
      certain rare tumors such as lymphoma, leukemia, or sarcoma, has been shown to be
      responsible for the development of colorectal carcinomas. The colorectal cancer
      phenotype undoubtedly originates from an accumulation of different genetic
      alterations. The nature of these alterations, their order of appearance, and
      their associations vary greatly from one tumor to another, suggesting that the
      concept of a unique model of carcinogenesis is not applicable to these tumors. We
      studied a panel of 40 colorectal tumors in an attempt to identify different
      carcinoma subsets distinguishable by the pattern of genetic alterations. We
      examined a series of genetic anomalies frequently implicated in the development
      of colorectal cancer, including genetic material loss, demonstrated by loss of
      heterozygosity on chromosome arms 1p, 17p, and 18q; mutations of proto-oncogene K
      RAS codons 12, 13, and 61; and gene TP53 mutations, identified by studying the
      accumulation of the corresponding immunohistochemically detectable protein. Our
      findings showed an important correlation between the genetic material loss events
      and an independent distribution of point mutations, which favors the hypothesis
      of a specific type of genetic instability characterized by the recurrent loss of
      chromatin fragments implicated in a subset of colorectal cancers.

PMID- 9648556
TI  - Cytogenetic analysis of hepatoblastoma: hypothesis of cytogenetic evolution in
      such tumors and results of a multicentric study.
AB  - Hepatoblastoma is a rare pediatric malignant tumor of the liver. Previous
      cytogenetic reports are sporadic. We karyotyped nine consecutive hepatoblastomas
      from the Italian centers participating in a multicentric study on hepatic tumors
      (SIOPEL 1). Six cases showed abnormal karyotypes. The most common abnormalities
      were trisomies of chromosomes 2 and 20. Four cases showed abnormalities of
      chromosome 1. On the basis of findings, we speculate the possibility of a
      cytogenetic evolutive pattern of hepatoblastomas.

PMID- 9648557
TI  - Frequency of clonal B lymphocytes in chronic myelogenous leukemia evaluated by
      fluorescence in situ hybridization.
AB  - The demonstration of the Philadelphia (Ph) chromosome in B lymphocytes from
      patients with chronic myelogenous leukemia (CML) has provided evidence that the
      disorder originates in a pluripotent progenitor cell. Divergent results, however,
      exist as to the degree of contribution of clonally derived cells to the B-cell
      compartment. To address this issue, B lymphocytes were selected from the blood of
      seven patients in the chronic phase of Ph-positive CML and were examined with
      dual-color fluoresence in situ hybridization for the presence of the Ph
      translocation. The purity of the B-cell preparations ranged from 88% to 97% (mean
      93%). The Ph translocation was detected in 22-34% (mean, 27%) of the sorted B
      cells. There was no evidence that the duration of the disease affects the ratio
      of Ph-positive and -negative B cells. In summary, clonally derived circulating B
      lymphocytes were present in all patients studied but made only minor contribution
      to this compartment.

PMID- 9648558
TI  - Search for chromosome instability in lymphocytes with germ-line mutations in DNA
      mismatch repair genes.
AB  - All colorectal cancer results from the accumulation of critical genetic
      alterations; however, the mechanisms of acquiring these mutations appear to be
      different in hereditary nonpolyposis colon cancer (HNPCC) and sporadic tumors
      with microsatellite instability compared with sporadic tumors with no
      microsatellite instability. To further explore the possible mechanisms of cancer
      predisposition in HNPCC, we studied chromosome breakage and induction of
      aneuploidy in the lymphoblastoid cell lines of four patients who were
      heterozygous for mutations in either hMSH2 or hMLH1--two components of the DNA
      mismatch repair complex. Cells were cultured under different stress systems,
      including exposure to bleomycin, mitomycin C, bromodeoxyuridine-induced sister
      chromatid exchange, and a DNA alkylator, N-methyl-N'-nitro-N-nitrosoguanidine. No
      significant differences were detected in the levels of major or minor chromosome
      breakage or aneuploidy compared with controls. These results suggest that a
      single "hit" to a DNA mismatch repair gene does not confer appreciable
      susceptibility to structural or numerical chromosomal alterations, which is
      consistent with previous observations that HNPCC-related cancers are more likely
      to be near diploid than are sporadic colon cancers.

PMID- 9648559
TI  - Cytogenetic analysis of a scapular chondromyxoid fibroma.
AB  - Chondromyxoid fibroma (CMF) is a rare cartilaginous tumor of bone. It typically
      presents in the lower extremities of young males. Cytogenetic analysis of two
      chondromyxoid fibromas has been previously reported. We studied a scapular CMF
      from an 11-year-old female by cytogenetic and molecular cytogenetic methods and
      found an unbalanced reciprocal translocation between the short arm of chromosome
      3 and the long arm of chromosome 6. In this translocation, several bands from
      chromosome 3 (3p12, 3p13, 3p14, 3p21) are lost and several bands on chromosome 6
      (6q21, 6q22, 6q23) appear rearranged. Two known cartilage-related genes are
      located in the regions affected by this unbalanced rearrangement: the type X
      collagen gene (COL10A1) located at 6q21-q22 and the parathyroid
      hormone/parathyroid hormone-related peptide receptor gene (PTH/PTHrP) located at
      3p21.1-p22. These genes function to control growth and maturation of endochondral
      bone, the site of origin of cartilaginous tumors.

PMID- 9648560
TI  - The ABL/BCR fusion gene on chromosome 9 in Ph-negative chronic myelogenous
      leukemia: a case for vigilance in fluorescence in situ hybridization
      interpretation.
AB  - We report cytogenetic, fluorescence in situ hybridization (FISH), and molecular
      analysis in a case of Ph-negative chronic myelogenous leukemia patient with
      ABL/BCR fusion gene on chromosome 9 and a disparate FISH signal pattern using two
      commercially available bcr/abl probes (Vysis, Inc. and Oncor, Inc.). Cytogenetic
      analysis revealed a 46,XX normal female karyotype. FISH studies using Vysis LSI
      bcr/abl probe in interphase cells demonstrated a BCR/ABL fusion pattern, similar
      to that of m-BCR/ABL fusion found in acute lymphoblastic leukemia. However,
      examination of metaphases revealed the ABL/BCR fusion signal on one of the
      chromosomes 9, an ABL signal on the other chromosome 9, and two BCR signals of
      different sizes on each of the chromosomes 22. Subsequently, a FISH study with
      the Oncor major (M)-bcr/abl translocation probe confirmed the ABL/BCR fusion
      signal on chromosome 9 in addition to an ABL signal and a BCR signal located on
      chromosomes 9 and 22, respectively. Molecular studies (RT-PCR) revealed a
      rearrangement of the M-BCR region and expression of a chimeric bcr/abl mRNA of
      b3a2 configuration. This case suggests that it is imperative to have a full
      understanding of both the capabilities and the limitations of bcr/abl
      translocation probes and that FISH interphase signals should be confirmed on
      metaphase spreads for accurate diagnosis.

PMID- 9648561
TI  - Isochromosome 7q and Wilms tumor.
AB  - Isochromosome 7q is a nonrandom cytogenetic abnormality in Wilms tumor. Two
      notable cases are described: (1) a case of bilateral Wilms tumor in which only
      the left-sided tumor contained isochromosome 7q and (2) a case of left-sided
      Wilms tumor in which the tumor contained isochromosome 7q, in addition to four
      other chromosomal abnormalities associated with Wilms tumor.

PMID- 9648562
TI  - Translocation (3;21;8)(q21;q22;q22) in a patient with acute myeloid leukemia. A
      case report and review of prognostic indicators.
AB  - We report a patient with acute myeloid leukemia (AML) and t(3;21;8)(q21;q22;q22).
      This translocation has not been previously described in de novo or relapsed AML.
      The patient is a 25-year-old woman who presented with WBC 6.2 x 10(9)/L, Hgb 10.2
      g/dL, Hct 28.4%, and platelets 67 x 10(9)/L. A bone marrow biopsy revealed a 70%
      hematopoietic cellularity with 65% blasts. Immunophenotyping showed aberrant
      expression of lymphoid-associated marker CD19. Cytogenetic analysis on a 72-hour
      culture of bone marrow cells supplemented with conditioned media was evaluated by
      G-banding at about the 400-band level. The patient's age, cytogenetics, WBC, and
      immunophenotype at diagnosis would seem to suggest a favorable prognosis,
      according to previous studies of prognostic indicators. She was treated with
      induction and consolidation chemotherapy, followed by myeloablative conditioning
      and autologous peripheral blood stem cell transplant (PBSCT). Despite multiple
      favorable prognostic factors, the patient relapsed 7 months after PBSCT.
      Translocation of chromosomes 8 and 21 is common in AML and is generally
      considered a good prognostic factor. We suspect that the effect of the 3q21
      translocation in an otherwise favorable translocation of chromosomes 8 and 21 may
      be responsible for this patient's early relapse.

PMID- 9648563
TI  - A novel t(7;17)(q11;q11) as the sole karyotypic abnormality in childhood pre-B
      cell acute lymphoblastic leukemia.

PMID- 9648564
TI  - Translocation (9;22;21) in a chronic myeloid leukemia fluorescence in situ
      hybridization definition.

PMID- 9648565
TI  - Distinct features for chromophilic renal cell cancer with Xp11.2 breakpoints.

PMID- 9648566
TI  - Improvement of infraorbital hyperpigmentation following carbon dioxide laser
      resurfacing.
AB  - BACKGROUND: Many patients who request cutaneous carbon dioxide (CO2) laser
      resurfacing for correction of periorbital rhytides also complain of "dark
      circles" under their eyes. OBJECTIVE: This study was conducted in order to
      determine the effectiveness of high-energy pulsed CO2 laser treatment in reducing
      infraorbital hyperpigmentation. RESULTS: Significant lightening of infraorbital
      hyperpigmentation was observed 9 weeks following CO2 laser resurfacing. Melanin
      reflectance spectrometry readings did not correlate with clinical findings.
      CONCLUSIONS: This study represents the first report of the successful use of a
      non-pigment-specific laser system for the treatment of infraorbital dark circles.
      The lack of correlation of melanin spectrometry readings with clinical assessment
      likely represents an insufficient follow-up time period.

PMID- 9648567
TI  - Treatment of photoaged neck skin with the pulsed Erbium:YAG laser.
AB  - BACKGROUND: The Erbium (Er):YAG laser represents a new laser approach for the
      treatment of rhytids and photodamaged skin. Because the Er:YAG laser's 2940-nm
      wavelength is at the peak of water absorption, this laser produces minimal
      thermal damage. OBJECTIVE: To document the Er:YAG laser's efficacy in the
      treatment of neck rhytids. METHODS: Ten patients with neck rhytids were treated
      with the Er:YAG laser. All individuals were evaluated for clinical improvement,
      scarring, and pigmentary changes. RESULTS: All patients showed fair to excellent
      results with no scarring or pigmentary changes at 6 months. CONCLUSION: The
      Er:YAG laser may be used to improve nonfacial photodamaged skin.

PMID- 9648568
TI  - Rapid Fire Hair Implanter Carousel. A new surgical instrument for the automation
      of hair transplantation.
AB  - BACKGROUND: As hair transplantation evolved into a procedure in which large
      numbers of very small grafts are moved in a single session, new problems have
      emerged. These include greater staffing requirements, longer operating time,
      additional technical difficulties, and increasing problems with quality control.
      OBJECTIVE: To introduce a new surgical instrument, the Rapid Fire Hair Implanter
      Carousel (Carousel), which can automate the most labor-intensive parts of the
      hair transplantation process, site creation and implant placement, by combining
      them into a single step and delivering them in rapid sequence. This
      instrumentation should help to minimize some of the human factors contributing to
      graft injury and to simplify and increase the speed of the hair transplant
      procedure. METHODS: In a patient with a Norwood IIIA balding pattern, 400
      follicular implants were placed into a specific section of the bald scalp. The
      remainder of the bald scalp was transplanted with 800 follicular implants placed
      in the traditional way. The two areas were monitored and compared for
      intraoperative bleeding, ease of placing, total placing time, postoperative
      healing, and hair growth. Photographic documentation was obtained after surgery
      and at each postoperative visit. RESULTS: The Carousel visually produced less
      bleeding when compared with the manual approach. The Carousel was easier to use
      than the manual technique, since it eliminated graft insertion as a separate
      step. This was evidenced by the significantly shorter time required to insert the
      implants (40 grafts/minute with the Carousel vs 6.6 grafts/minute manually) and
      the decreased need for secondary manipulation once the grafts were inserted.
      Postoperative healing of the two groups were the same with regard to the duration
      of crusting and erythema. The rate of hair growth and the total amount of hair
      observed at 4 months were the same when identical size areas in test and control
      sides were compared. CONCLUSION: In this single patient pilot study, the Carousel
      greatly facilitated the placement of grafts by decreasing bleeding and obviating
      the extra step needed for the insertion of the implants. As a result, the total
      operative time decreased, shortening the time the grafts were outside the body,
      and decreasing the risk of desiccation and warming. By minimizing the human
      factor in this labor-intensive part of the procedure, the quality of the hair
      transplant should increase. It is anticipated that these benefits will result in
      increased hair yield. Further studies are needed, in a larger patient group, so
      that these benefits can be demonstrated.

PMID- 9648569
TI  - New instrumentation for hair transplantation surgery.
AB  - This article introduces new instrumentation to the field of hair transplantation
      surgery. These new instruments include differential spear blades for better
      sharpness and versatility, a graft counter for facilitation of the counting
      process, a blade holder with a direction guide to help the doctor with proper
      direction of recipient incisions, a cushioned forceps to soften the trauma to the
      hair grafts as they are being inserted, a compass to help construct the posterior
      crown, and a temperature probe that constantly monitors the temperature of the
      saline solution that is keeping the hair grafts cool. This instrumentation has
      significantly facilitated and improved the hair transplantation process.

PMID- 9648570
TI  - Alabaster skin after carbon dioxide laser resurfacing with histologic
      correlation.
AB  - BACKGROUND: Carbon dioxide laser resurfacing has gained popularity as a
      relatively safe and effective method of facial rejuvenation. Original reports
      describe mostly reversible side effects and a low incidence of scarring. Only
      very recently have reports of delayed hypopigmentation surfaced. This effect is
      not visible until several months after resurfacing, and most likely represents a
      permanent change. OBJECTIVE: To provide an additional clinical description of the
      complication of delayed hypopigmentation along with the first published
      histologic correlation. METHODS: Clinical records along with a preprocedure and 7
      month postprocedure full-thickness skin biopsy were used for this report.
      RESULTS: This patient experienced a striking leukoderma 6 months after a full
      facial carbon dioxide laser resurfacing procedure done for widespread actinic
      keratoses. There was a zone of dermal fibrosis extending approximately 0.4 mm on
      the postprocedure biopsy. Comparison of the preprocedure and postprocedure
      biopsies revealed no difference in the number of melanocytes by MART-1
      immunohistochemical staining, but there was a significant decrease in epidermal
      melanin as determined by Fontana-Mason staining. CONCLUSION: This patient
      experienced a profound expression of an increasingly recognized and reported
      complication of carbon dioxide laser resurfacing. Histologic correlation is
      similar to the results previously reported after phenol chemical peels,
      demonstrating a normal number of melanocytes but a decrease in epidermal melanin.

PMID- 9648571
TI  - The roles of pH and concentration in lactic acid-induced stimulation of epidermal
      turnover.
AB  - BACKGROUND: Alpha hydroxy acids such as lactic and glycolic acids (AHAs)
      accelerate epidermal turnover and exfoliate the stratum corneum. The roles of pH
      and concentration in these antiaging effects of AHAs is unclear, but a lower
      (more acidic) pH and higher concentration of acid are thought to be more
      effective. OBJECTIVE: To examine the effects on skin renewal rates of lactic acid
      10% at pHs of 2.0, 3.0, and 4.0, and of 5%, 10% and 15% lactic acid at a pH of
      3.0. METHODS: Twenty-six female subjects participated in the double-blind,
      randomized, placebo-controlled study. The dansyl chloride stain technique was
      used to measure epidermal renewal times. RESULTS: Both pH and concentration are
      critical in the lactic acid effect. At a fixed lactic acid concentration, the
      desquamative effect was highly pH dependent. At a fixed pH, the turnover rate of
      skin was concentration dependent. CONCLUSION: The desquamative and proliferation
      stimulating effects of lactic acid are very pH and concentration dependent,
      suggesting the "free acid" concentration is the active moiety.

PMID- 9648572
TI  - Comparison of high-energy pulsed carbon dioxide laser resurfacing and
      dermabrasion in the revision of surgical scars.
AB  - BACKGROUND: Both dermabrasion and high-energy pulsed carbon dioxide (CO2) laser
      resurfacing can improve the appearance of surgical scars. Although the results of
      these two procedures have been compared using historical data, a prospective
      evaluation has never been performed in humans. OBJECTIVE: To prospectively
      compare the clinical effects of dermabrasion and high-energy pulsed CO2 laser
      resurfacing in the revision of surgical scars. METHODS: Facial surgical scars in
      four patients were prospectively revised using a split scar model. One half of
      the scar was dermabraded and the other half was resurfaced with the high-energy
      pulsed CO2 laser. Comparisons of the two treatment modalities were performed
      through clinical assessment, photographic evaluation, and textural analysis of
      the scars. RESULTS: The high-energy pulsed CO2 laser-resurfaced halves of the
      scar were bloodless with less postoperative crusting in comparison with the
      dermabraded halves. Reepithelialization time and degree and duration of
      postoperative erythema were similar for both treatment halves. Photographic
      evaluation and textural analysis showed comparable improvement in the clinical
      appearance and surface texture of the scars with both treatment modalities.
      CONCLUSIONS: Both the high-energy pulsed CO2 laser and dermabrasion can achieve
      comparable clinical improvement in the revision of surgical scars. The high
      energy pulsed CO2 laser offers the advantage of a bloodless field and a more
      precise method of tissue ablation. Postoperative erythema, however, is an
      expected finding with both treatment modalities.

PMID- 9648573
TI  - Skin resurfacing of the face with the Erbium:YAG laser.
AB  - BACKGROUND: Laser resurfacing of facial skin is a very popular method of rhytide
      and scar removal. Until recently, the most effective tool utilized for these
      purposes was the pulsed char-free carbon dioxide laser. These lasers, however,
      produce thermal damage related to prolonged wound healing. The Erbium (Er): YAG
      laser, with its 2940-nm wavelength and maximal water absorption, has been
      recently introduced for laser resurfacing of the facial skin. OBJECTIVE: In this
      study, specific parameters for Er:YAG laser treatment of rhytides were evaluated
      clinically and histologically. METHODS: Fifteen patients were treated with the
      Er:YAG laser. Perioral, periorbital, and total face rhytides were treated. All
      patients were treated with 0.8-1.0 J, 5-mm spot size, with the final fluences of
      4-5 J/cm2. Patients were evaluated daily after treatment for 7 days and weekly
      for 2 months for erythema, healing time, improvement, and pigmentary changes.
      Histologic evaluation of preauricular human facial ex vivo skin was done to
      determine the penetration of multiple passes of Er:YAG laser in human facial
      skin. RESULTS: All patients showed some degree of improvement of their rhytides.
      Reepithelialization occurred between 3 and 8 days. All evidence of erythema
      resolved between 3 and 6 weeks after treatment. The level of tissue ablation was
      determined to be down to: the granular layer after one pass; to the basal cell
      layer after two passes, to the papillary dermis after three to four passes, and
      deeper into the papillary and superficial reticular dermis after five to six
      passes. CONCLUSION: The Er:YAG laser plays a significant role in the treatment of
      superficial and mid-depth rhytides.

PMID- 9648574
TI  - Accelerated laser resurfacing wound healing using a triad of topical
      antioxidants.
AB  - BACKGROUND: The speed of wound healing and the duration of erythema are the
      primary complaints after laser skin resurfacing. Antioxidants have been shown to
      enhance the healing of wounds by reducing free radical damage.
      Reepithelialization is also enhanced by the moist environment produced by
      occlusive dressings. OBJECTIVE: This study was conducted to compare two occlusive
      agents: white petrolatum and "melting" petrolatum. Another arm of the study
      evaluated the use of melting petrolatum with and without a triad of topical
      antioxidants (TTA). RESULTS: Plain white petrolatum proved superior to melting
      petrolatum in time required for reepithelialization as well as in discomfort.
      Crusting and pain were decreased with white petrolatum but duration of erythema
      was equivalent. Wound healing was enhanced when TTA was added. Time for
      reepithelialization, duration of crusting and scabbing, pain, redness, and
      swelling were decreased when TTA was added to topical therapy. CONCLUSION: TTA
      compound enhances and hastens wound healing. White petrolatum as a base occlusive
      vehicle shortens reepithelialization compared with "melting" petrolatum.

PMID- 9648575
TI  - Carbon dioxide laser resurfacing: preliminary observations on short-term follow
      up. A subjective study of 100 patients' attitudes and outcomes.
AB  - BACKGROUND: Carbon dioxide (CO2) laser resurfacing is enjoying broad medical
      acclaim. It is useful to assess patient morbidity and satisfaction with this
      procedure. OBJECTIVE: Review the procedure from the patients' perspective with
      particular focus on the immediate and medium term postoperative period, the
      patient's progress after the initial 6-8-week period, the postoperative morbidity
      and complication rate, and the results and patient satisfaction with the
      procedure. METHOD: One hundred resurfacing patients, who were treated after the
      advent of the computer pattern generator on a high-energy short-pulse CO2 laser,
      were studied. Patients were at least 3 months into their postoperative phase.
      RESULTS: Outcomes of patients' problems were classed as good to excellent 78.8%
      of the time. Patient outcomes met the patients' preoperative expectations 68.9%
      of the time. Patients would have the procedure again if needed 78% of the time,
      and 84% would recommend the procedure to others. Patients reported continuing
      improvement after the initial 6-8-week healing period 72% of the time. Short-term
      morbidity was high (49%). Long-term complications were registered in 7% of
      patients but were mostly minor in nature. CONCLUSIONS: Major indications for
      laser resurfacing such as wrinkles, sun damage, and acne scarring all appeared to
      do well with CO2 laser resurfacing.

PMID- 9648576
TI  - Mohs micrographic surgery for lentigo maligna and lentigo maligna melanoma. A
      follow-up study.
AB  - BACKGROUND: We previously reported our experience using Mohs micrographic surgery
      (MMS) for 45 patients with lentigo maligna (LM) and lentigo maligna melanoma
      (LMM). The patients were treated between 1985 and 1992. In our initial
      publication, all of the patients were free of local disease and evidence of
      metastases at an average of 29.2 months after therapy. OBJECTIVE: The purpose of
      this study was to report long-term follow-up of our previously published data.
      METHODS: MMS was performed in 26 patients with LM and 19 patients with LMM using
      frozen sections followed by rush permanent sections. Follow-up was obtained by
      contacting the referring physician, examination by one of our two Mohs surgeons,
      or by contacting the patient or his or her family. RESULTS: After a median follow
      up of 58.0 months (214.3 patient-years), there was one recurrence. This patient
      was a 56-year-old woman with five prior recurrences before MMS. Six patients were
      decreased of other causes during the study. CONCLUSIONS: MMS using frozen and
      rush permanent sections resulted in a 97% cure rate for LM and LMM. Because MMS
      minimizes the removal of normal tissue, and the cure rate exceeds that of
      conventional therapies, the authors recommend this technique for the treatment of
      LM and LMM.

PMID- 9648577
TI  - Hair tie-over dressing. A simple dressing for hair-bearing scalp wounds.
AB  - OBJECTIVE: To describe a temporary dressing for Mohs micrographic surgery wounds
      of the hair-bearing scalp. METHOD: The technique of using hair at the wound edges
      to hold down the dressing is described. RESULTS: This is an effective, simple,
      comfortable, and inexpensive scalp dressing, which our patients have found to be
      very acceptable. CONCLUSION: We consider that the hair tie-over dressing is an
      ideal temporary dressing for Mohs micrographic surgery wounds of the hair-bearing
      scalp.

PMID- 9648578
TI  - Mohs micrographic surgery for an erosive adenomatosis of the nipple.
AB  - BACKGROUND: Erosive adenomatosis of the nipple is a rare but distinct benign
      tumor of the nipple. It is usually considered to be derived from the apocrine
      sweat ducts of the nipple epithelium but probably of lactiferous duct origin.
      Total excision is the treatment of choice. OBJECTIVE: We report the clinical and
      histological features of this rare tumor, and the surgical technique employed.
      METHODS: Treatment consisted of Mohs micrographic surgery (MMS), fresh tissue
      technique, followed by primary closure. RESULTS: The described procedure resulted
      in a cure of the erosive adenomatosis of the nipple. CONCLUSION: Total excision
      of erosive adenomatosis of the nipple can be obtained by MMS. This technique
      prevents recurrence of the disease and minimizes resulting deformation of this
      important anatomic area.

PMID- 9648579
TI  - Laser resurfacing hysteria. The media, the marketers, the companies, and us.

PMID- 9648580
TI  - The limitations of skin resurfacing techniques. The necessity to combine
      procedures.

PMID- 9648581
TI  - Titanic tumescent anesthesia.

PMID- 9648582
TI  - Electrocautery for treating periorbital syringomas.

PMID- 9648583
TI  - The International Society for Dermatologic Surgery's Traveling Chair of
      Dermatologic Surgery Faculty and its newest member.

PMID- 9648584
TI  - Multidisciplinary management of urinary pouch complications: a better way.

PMID- 9648585
TI  - Management of early and late complications of ileocolonic continent urinary
      reservoir (Miami pouch).
AB  - PURPOSE: The object of this study is to review our experience and formulate a
      plan for early recognition and effective management of early and late
      complications seen in patients who have undergone construction of the ileocolonic
      continent urinary reservoir. METHOD: Charts of patients who underwent continent
      urinary diversion at the Division of Gynecologic Oncology, University of Miami
      School of Medicine, from 1988 to 1996 were reviewed. We analyzed our data in
      terms of early and late (beyond 6 weeks) complications resulting directly from
      the operation or from this form of urinary diversion. RESULTS: Urinary diversion
      via the continent ileocolonic reservoir has been performed at our institution
      since February 1988. Sixty-six women have undergone construction of the Miami
      pouch over the past 81 years. Sixty-three of 66 patients needed a reservoir as a
      part of total pelvic exenteration for persistent or recurrent gynecologic
      malignancy. Three patients underwent reservoir construction for repair of
      vesicovaginal fistula. Sixty-two of 66 patients (95%) have a history of prior
      pelvic radiation. A total of 35 patients (53%) suffered early complications
      resulting in an operative mortality rate of 9% (6 of 66 patients). Early
      complications related to the construction of the reservoir included ureteral
      stricture/obstruction [10], anastomotic leak [4], reservoir-cutaneous fistula
      [4], difficulty in catheterization [5], pyelonephritis [10], sepsis [6], DIC [2],
      and ARDS [1]. Nonsurgical management strategies used for reservoir-related
      complications in these cases included percutaneous nephrostomy, peripheral
      hyperalimentation, intravenous antibiotics, and ultrasound-guided catheter
      placement. Eighty-four percent (16/19) of functional complications of the
      reservoir resolved with conservative management, whereas 3/19 patients needed
      surgical revision. One or more late complications (beyond 6 weeks) occurred in 25
      patients (37%). Late complications seen included ureteral stricture/obstructions
      [6], incontinence [8], difficulty in catheterization [7], and urinary stones [4].
      Nonsurgical management strategies used included percutaneous nephrostomy, balloon
      dilation, scheduled catheterization, ultrasound-guided catheter placement, and
      endoscopic/percutaneous lithotripsy. Four of 25 patients needed reoperation,
      whereas in 84% (21/25) of patients problems resolved with initial conservative
      management. CONCLUSION: Successful conservative therapy constitutes establishment
      of drainage, adequate nutrition, avoidance of sepsis, close observation, and
      patience. This article reviews the complications of the continent ileocolonic
      form of urinary diversion and formulates a treatment outline emphasizing an
      initial conservative approach that offers optimal management of early and late
      complications seen in this patient group.

PMID- 9648586
TI  - Determination of a normal level of serum CA125 in postmenopausal women as a tool
      for preoperative evaluation and postoperative surveillance of endometrial
      carcinoma.
AB  - In an attempt to determine a normal level of CA125 in postmenopausal women, CA125
      levels of normal postmenopausal women (n = 36, 58.2 +/- 8.1 years) and
      postmenopausal women undergoing hormone replacement therapy (HRT) (n = 111, 56.8
      +/- 6.1 years) were studied. A mean CA125 concentration of 10.0 +/- 3.8 U/ml was
      found in postmenopausal women without HRT and was significantly lower than that
      of postmenopausal women undergoing HRT (12.8 +/- 3.8 U/ml), indicating that the
      cutoff level of CA125 in postmenopausal women or women without reproductive
      organs should be estimated at a level lower than that conventionally accepted. A
      receiver operating characteristic (ROC) curve for a preoperative evaluation of
      myometrial invasion was analyzed in postmenopausal women with endometrial cancer
      (n = 110). A novel cutoff level of 20 U/ml of CA125 could detect myometrial
      invasion to more than one-half of the myometrium with sensitivity of 69.0%,
      specificity of 74.1%, positive predictive value of 58.8%, and negative predictive
      value of 81.6%. In addition, the distribution of CA125 levels was analyzed in
      patients who had undergone an operation for endometrial cancer more than 2 years
      earlier and as yet had no clinical evidence of recurrence of the disease. Ninety
      six point two percent of 619 measurement values were lower than 20 U/ml. These
      results suggest that the novel CA125 level of 20 U/ml is clinically useful for
      preoperative evaluation and postoperative surveillance of endometrial carcinoma.

PMID- 9648587
TI  - In vivo studies of adenovirus-based p53 gene therapy for ovarian cancer.
AB  - OBJECTIVES: To test the safety, efficacy, and toxicity of gene therapy using wild
      type p53-expressing adenovirus (Ad-CMV-p53) in a nude mouse model with
      intraperitoneal (i.p.) 2774 human ovarian cancer cell line that contains a p53
      mutation. STUDY DESIGN: An initial study of adenovirus tolerance was determined
      in nude mice by a single i.p. injection of increasing doses of Ad-CMV-p53. Nude
      mice were implanted with an LD100 dose of 1 x 10(7) cells. To study the efficacy
      and specificity of Ad-CMV-p53 treatment, the mice received treatment with
      different adenovirus constructs. One group received Ad-CMV-p53 and another group
      received a control adenovirus construct, Ad-CMV-beta gal. To study the treatment
      response to Ad-CMV-p53, the mice were divided into groups and received various
      treatment schedules of 1 x 10(8) pfu of Ad-CMV-p53. RESULTS: The mice tolerated
      Ad-CMV-p53 without adverse effects at doses of 1 x 10(8) pfu. The response to Ad
      CMV-p53 showed significant survival duration in each dose regimen, with a
      survival time greater than that of untreated animals (P = 0.0173). However, no
      statistically significant survival advantage was observed between Ad-CMV-p53- and
      Ad-CMV-beta gal-treated mice. CONCLUSIONS: These studies show that at the
      adenovirus dose and administration regimen used, there is effective but not
      specific 2774 tumor growth inhibition in vivo. Efficient introduction of
      biologically active genes into tumor cells would greatly facilitate cancer
      therapy. Thus, although promising, these results caution that much effort will be
      required to realize the potential for clinical application of adenovirus-based
      ovarian cancer gene therapy.

PMID- 9648588
TI  - The status of human papillomavirus and tumor suppressor genes p53 and p16 in
      carcinomas of uterine cervix from India.
AB  - OBJECTIVES: Infection with the high-risk strain of human papillomaviruses (HPVs)
      and the inactivation of the tumor suppressor gene p53 through mutation are
      important factors in cervical carcinogenesis. To know whether such events would
      occur in cervical carcinomas of Indians, 43 tumors (consisting of 36 of stage III
      B and 6 of stage II B) were screened for p53 and p16 gene mutations. METHODS: PCR
      followed by single-strand conformation polymorphism (SSCP) analysis were used to
      detect mutations in p53 and p16 genes and PCR for the presence of human
      papillomavirus genome. HPV status was ascertained by PCR amplification of parts
      of E6 and E7 genes using primers pU-1M and pU-2R and typing was carried out by
      restriction analysis. RESULTS: Of the 43 samples analyzed, 4 samples (9%) showed
      mobility shifts for p53 mutations; PCR products of the p16 gene did not show band
      shifts in SSCP analysis. HPV DNA was detected in 70% of the 43 samples analyzed:
      HPV 16 in 23 cases (53%), HPV 18 in 4 cases (13.3%), and HPV 33 in 1 case (3.3%).
      Two amplified HPV DNAs that were difficult to type with various restriction
      enzymes were cloned and the amplified regions were sequenced. One of these was
      93% close to HPV 35 and the other was 80% close to HPV 58. Three samples had both
      p53 mutations and HPV genome. CONCLUSIONS: Our results indicate that HPV 16
      infection was more common than HPV 18, the p53 mutations and HPV infection were
      not mutually exclusive events in the genesis of carcinoma of uterine cervix among
      Indian women, and p16 gene may not play a role in Indian cervical carcinomas.

PMID- 9648589
TI  - No evidence for microsatellite instability from allelotype analysis of benign and
      low malignant potential ovarian neoplasms.
AB  - The genetic events that lead to the development of benign and low malignant
      potential (LMP) tumors from normal ovarian surface epithelium are not well
      understood. In contrast to invasive ovarian neoplasms, loss of heterozygosity
      (LOH) is not common in these tumors except on the X chromosome, but one report
      has suggested that an alternative genetic mechanism, microsatellite instability
      (MSI), might be an important pathogenic mechanism for LMP ovarian tumors.
      OBJECTIVE: To determine the frequency of MSI in LMP tumors and to detect novel
      regions of LOH in benign and LMP ovarian tumors. METHODS: Sixty-nine
      microsatellite markers were analyzed in 23 benign and 31 LMP ovarian tumors.
      RESULTS: No evidence of MSI was found in any of the tumors studied, nor were any
      novel regions of LOH identified. CONCLUSIONS: This suggests that new approaches
      may be necessary to understand the genetic basis of benign and LMP ovarian
      neoplasms since neither LOH nor MSI appears to play a major role.

PMID- 9648590
TI  - Retinoblastoma protein expression in ovarian epithelial neoplasms.
AB  - Progress has been made in identifying the molecular changes that occur in ovarian
      carcinoma; still our understanding of these changes and their interactions
      remains incomplete. In the present study the authors examined the expression of
      retinoblastoma protein, a tumor suppressor protein, in a spectrum of ovarian
      epithelial tumors including cystadenomas, low-malignant-potential tumors, and
      carcinomas. A heterogeneous pattern of reactivity was observed in all of the
      cystadenomas, in all of the low-malignant-potential tumors, and in a majority
      (27/34) of the carcinomas. The remaining carcinomas showed either a complete
      absence of reactivity or a pattern of altered reactivity characterized by areas
      of tumor with intact reactivity adjacent to zones of tumor with a complete
      absence of reactivity. There was no significant association between grade or
      stage and absent/altered reactivity. We conclude that alterations of
      retinoblastoma protein expression are uncommon in ovarian carcinoma.

PMID- 9648591
TI  - Prognostic significance of progesterone receptor immunohistochemistry in
      endometrial carcinoma.
AB  - OBJECTIVE: The aim of this study was to evaluate the prognostic significance of
      steroid hormone receptors in endometrial carcinoma using immunohistochemical
      staining for progesterone receptor (PR) and estrogen receptor (ER). METHODS: We
      evaluated the correlation between PR/ER immunohistochemistry and age, clinical
      stage, tumor grade, myometrial tumor invasion, and disease-free survival in a
      series of 92 cases of endometrioid adenocarcinoma. RESULTS: Fifty (54.4%)
      endometrial carcinomas were PR-positive and 44 (47.8%) were ER-positive. PR
      immunohistochemistry of endometrial carcinoma was statistically correlated with
      the International Federation of Gynecology and Obstetrics (FIGO) stage (I, II vs
      III, IV, P = 0.001), FIGO grade (G1 vs G2 vs G3, P = 0.007), the depth of
      myometrial tumor invasion (< or = 1/2 vs > 1/2, P = 0.006), and disease-free
      survival (living vs dead, P = 0.0025). In contrast, ER immunohistochemistry had
      significant correlations with the depth of myometrial tumor invasion (P = 0.026)
      and disease-free survival (P = 0.032). Multivariate analysis of PR/ER
      immunohistochemistry, stage, grade, and myometrial invasion showed that the PR
      immunohistochemistry was a significant prognostic factor for survival (P =
      0.026). CONCLUSION: PR/ER immunohistochemistry was significantly related to
      survival and PR immunohistochemistry appeared to be the most reliable means for
      predicting survival in endometrioid adenocarcinoma of the endometrium,
      independent of other clinicopathological parameters.

PMID- 9648592
TI  - Altretamine (hexamethylmelamine) in platinum-resistant and platinum-refractory
      ovarian cancer: a Gynecologic Oncology Group phase II trial.
AB  - OBJECTIVES: In an effort to critically examine the antitumor activity of
      altretamine (hexamethylmelamine) as salvage therapy of platinum-refractory
      ovarian cancer, the Gynecologic Oncology Group initiated a Phase II trial of the
      agent administered in this clinical setting. METHODS: Altretamine was
      administered at a dose of 260 mg/m2 orally for 14 days in a 28-day course.
      Treatment was continued until disease progression or unacceptable side effects
      prevented further therapy. A total of 36 patients (median age: 56.5) were treated
      on this trial, of whom 33 were evaluable for toxicity and 30 for response. All
      patients had previously received either cisplatin or carboplatin and paclitaxel.
      RESULTS: The major side effect was emesis (grade 3-4, 7/33, 21%). The objective
      response rate was 10% (one complete response, two partial responses). CONCLUSION:
      We conclude that altretamine has limited activity in platinum-refractory ovarian
      cancer.

PMID- 9648593
TI  - Transforming growth factor-beta 1 induces apoptosis through down-regulation of c
      myc gene and overexpression of p27Kip1 protein in cervical carcinoma.
AB  - Transforming growth factor-beta 1 (TGF-beta 1) is known to be a potent growth
      inhibitor for many cell types, including most epithelial cells. In skin
      keratinocytes, TGF-beta 1 has been shown to inhibit growth and to rapidly reduce
      c-myc expression. However, the molecular mechanism of TGF-beta 1 action on cell
      growth of cervical carcinoma has not yet been elucidated. We thus assessed the
      effect of TGF-beta 1 on the growth of cervical carcinoma cell lines. Two cervical
      squamous carcinoma cell lines, CUMC-3 and CUMC-6, were incubated with varying
      concentrations of TGF-beta 1, and growth inhibition was evaluated with
      tetrazolium-based colorimetric assay. After culture in TGF-beta 1 for 24 h,
      inhibition of growth was detected in a dose-dependent manner at concentrations of
      0.1-10 ng/ml in both cell lines. This effect of TGF-beta 1 on cultured carcinoma
      cells was associated with apoptotic process including oligonucleosomal ladder DNA
      and apoptotic body formations. Northern blot analysis revealed c-myc mRNA
      expression was suppressed by 10 ng/ml of TGF-beta 1 following 3 h of treatment in
      both cell lines. Western blot analysis showed that the level of p27Kip1 protein
      was increased after TGF-beta 1 treatment in both cell lines. These results
      suggest that the mechanisms by which TGF-beta 1 inhibits the growth of cervical
      carcinoma are complex and may include effects on down-regulation of c-myc gene,
      and overexpression of p27Kip1 protein.

PMID- 9648594
TI  - "Medically necessary" panniculectomy to facilitate gynecologic cancer surgery in
      morbidly obese patients.
AB  - A retrospective review of patients in our practice who underwent abdominal
      panniculectomy to facilitate gynecologic cancer surgery was performed. The
      objective of the study was to determine if panniculectomy was a safe and useful
      procedure in the morbidly obese gynecologic cancer patient. A total of 12
      patients underwent the procedure between 1992 and 1996. Optimal pelvic oncologic
      surgery was accomplished in all 12 patients. All aspects of those procedures were
      performed by gynecologic oncologists. The Buchwalter retractor was used in all
      cases. The patients' weights ranged from 170 to 429 pounds, with a mean of 275
      pounds. The mean body mass index was 48, with a range from 37 to 67. Four
      patients had a history of diabetes mellitus. Nine patients healed without wound
      complications. Three patients developed superficial subcutaneous wound
      infections/necrosis that were successfully managed with office debridement.
      Abdominal panniculectomy is a reasonably safe procedure that makes radical pelvic
      surgery possible regardless of the patient's weight. Prolonged wound bulb suction
      drainage may decrease the incidence of wound necrosis/infection in these high
      risk patients.

PMID- 9648595
TI  - Cervical cancer with paraaortic metastases: significance of residual paraaortic
      disease after surgical staging.
AB  - Cervical carcinoma frequently metastasizes to the paraaortic region,
      necessitating extended field radiotherapy to effect a cure. As imaging modalities
      are unreliable in identifying all cases of paraaortic nodal metastases (PAN),
      surgical staging is often utilized prior to radiotherapy. This study was aimed at
      identifying factors predictive of survival in women with cervical carcinoma and
      paraaortic metastases. In particular, survival based on extent of paraaortic
      disease was examined. The study group consisted of 43 women (stages IB-IVB)
      identified between 1982 and 1993 who were treated with extended field radiation
      for cervical carcinoma with histologically confirmed paraaortic metastases. The
      estimated 5-year survival for the study population was 24% with a median survival
      of 18 months. Pelvic tumor size had a significant impact on survival with the
      median survival being 34 months if the primary lesion was < 6 cm compared to 14
      months if > or = 6 cm (P = 0.01). Eight of the 26 (31%) women without residual
      PAN disease after surgical staging remain alive and disease free (mean follow-up,
      74 months). In contrast, only 1 of the 17 (6%) women with gross residual PAN is
      alive 71 months after treatment (P = 0.05). However, a comparison of Kaplan-Meier
      survival curves did not show a statistically significant advantage to the
      surgical excision of grossly involved PAN (P = 0.98). Although long-term survival
      among women with grossly involved, unresected paraaortic metastases is uncommon,
      further study is necessary to elucidate the role of surgical excision of bulky
      aortic disease in women with cervical cancer.

PMID- 9648596
TI  - High serum levels of soluble IL-2 receptor, cytokines, and C reactive protein
      correlate with impairment of T cell response in patients with advanced epithelial
      ovarian cancer.
AB  - The serum levels of interleukin-(IL-)1 alpha, IL-1 beta, IL-2, IL-6, TNF alpha,
      and sIL-2R and the proliferative response of peripheral blood mononuclear cells
      (PBMC) to phytohemagglutinin (PHA), anti-CD3 monoclonal antibody (mAb),
      recombinant IL-2 (rIL-2), and the combination of PHA or anti-CD3 mAb with rIL-2
      were studied and correlated with serum levels of C-reactive protein (CRP) in
      women with advanced epithelial ovarian cancer. The expression of CD25 and CD122
      subunities of membrane-bound IL-2R on PHA- or anti-CD3 mAb-stimulated PBMC was
      also studied. In comparisons with the controls, PBMC response to PHA, anti-CD3
      mAb, and rIL-2 was significantly lower in the cancer patients. The addition of
      exogenous rIL-2 to the PBMC cultures increased response in both controls and
      patients but did not modify the significance of the differences. After
      stimulation with PHA or anti-CD3 mAb, the percentage of PBMC CD25+ or CD122+ was
      significantly lower in patients. The serum levels of IL-1 alpha, IL-1 beta, IL-6,
      TNF alpha, sIL-2R, and CRP were significantly increased in patients compared to
      the controls. Instead, no differences were observed for serum levels of IL-2. A
      strong association was found between high serum levels of the above-mentioned
      cytokines, sIL-2R, and CRP. The results of our study on advanced stage (IIIb-IV)
      ovarian cancer patients are consistent with the previously reported hypothesis
      that high IL-6 and/or CRP serum levels may represent an important and independent
      prognostic factor of the likely outcome in cancer patients.

PMID- 9648597
TI  - Evidence for a common etiology for endometrial carcinomas and malignant mixed
      mullerian tumors.
AB  - OBJECTIVE: To elucidate factors linked to the development of malignant mixed
      mullerian tumors (MMMT) and determine whether the risk factor profile for these
      tumors corresponds with that for the more common endometrial carcinomas. METHODS:
      A multicenter case-control study of 424 women diagnosed with endometrial
      carcinoma, 29 women diagnosed with MMMT, and 320 community controls was
      conducted. Review of pathological reports and slides was performed to classify
      cases by histological type. All participants were asked to respond to a
      questionnaire which ascertained information on exposure to factors postulated to
      be linked to the development of uterine tumors. RESULTS: Women with endometrial
      carcinomas and MMMTs were similar with respect to age and educational attainment.
      Women diagnosed with MMMTs were more likely than those diagnosed with carcinomas
      to be of African-American descent (28% vs 4%; P = 0.001). Weight, exogenous
      estrogen use, and nulliparity were related to risk of both tumor types. Marked
      obesity was associated with a 4.8-fold (95% CI = 3.0,7.6) increase in risk of
      carcinoma and a 3.2-fold (95% CI = 1.1,9.1) increase in risk of MMMT development.
      Use of exogenous estrogens increased the odds of developing carcinomas by 2-fold
      (95% CI = 1.3,3.2) and that of developing MMMTs by 1.8-fold (95% CI = 0.57,5.5).
      Nulliparity was associated with a 2.9-fold (95% CI = 1.9,4.8) increase in risk of
      carcinomas and a 1.7-fold (95% CI = 0.53,5.6) increase in risk of MMMTs. Oral
      contraceptive use protected against the development of both carcinomas (OR =
      0.39; 95% CI = 0.26,0.58) and MMMTs (OR = 0.76; 95% CI = 0.25,2.3). Current
      smokers were at a reduced risk of developing endometrial carcinomas (OR = 0.34;
      95% CI = 0.21,0.55) and MMMTs (OR = 0.57; 95% CI = 0.15,2.3), while former
      smokers were at an increased risk of MMMT (OR = 2.7; 95% CI = 1.1,6.8) but not
      carcinoma development (OR = 0.81; 95% CI = 0.56,1.2). CONCLUSION: Results from
      this study suggest that MMMTs and carcinomas have a similar risk factor profile.
      This observation is compatible with the hypothesis that the pathogenesis of these
      two histological types of uterine tumors is similar.

PMID- 9648598
TI  - Secondary response of ovarian tumors to topotecan treatment.
AB  - Three patients presented with ovarian cancer that was initially treated with
      paclitaxel and platinum-based compounds. Although responses to these agents
      occurred, tumor progression was evident by elevated CA 125 levels after a period
      of 11 to 35 months. These patients were then treated with topotecan and exhibited
      a response and stopped therapy. All patients subsequently had progression of
      disease. The patients were again treated with topotecan and have experienced
      favorable responses. All three patients are currently receiving treatment with
      topotecan and have stable disease. The results presented here suggest that re
      treatment with anti-tumor agents, such as topotecan, may be able to elicit a
      response in tumors previously sensitive to these agents.

PMID- 9648599
TI  - Ovarian mixed germ cell tumor composed of polyembryoma and immature teratoma.
AB  - We report the case of a 41-year-old woman with ovarian mixed germ cell tumor
      which was composed of polyembryoma and immature teratoma and who had high serum
      levels of alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG). By
      immunohistochemical methods, AFP was found in yolk sac cells of the embryoid
      bodies and immature hepatoid tissues, and hCG was found in giant
      syncytiotrophoblastic cells. She was treated with surgery followed by cisplatin
      based combination chemotherapy. She is well, and her serum levels of AFP and hCG
      have not been elevated for more than 4 years after the treatment.

PMID- 9648600
TI  - Cardiac metastasis from carcinoma of the cervix: report of two cases.
AB  - BACKGROUND: The presence of cardiac metastasis from cervical carcinoma is
      extremely rare. The diagnosis is made almost exclusively postmortem. There are
      few cases of premortem diagnosis, and it is believed that when cardiac metastasis
      are found in vivo, the prognosis is extremely poor. Due to the rarity of this
      condition it is very difficult to standardize care for these patients.
      Considering the evidence provided by the cases in this report, it is possible
      that aggressive therapy may lengthen patients survival and quality of life. CASE:
      We present two cases of cervical carcinoma with metastasis to the heart. Both
      patients presented with symptomatology of cardiac tamponade. Both patients had
      invasion of the myocardium from presumed endomyocardial metastasis where the
      prognosis is even worse. We took an aggressive therapeutic approach to our
      patients and had excellent results in one. Our report includes the longest
      survival reported for a patient to date with premortem diagnosis of
      intramyocardial metastasis from cervical carcinoma. CONCLUSION: We concluded that
      the prognosis for cardiac metastasis from cervical carcinoma is extremely poor.
      The stage of the disease at initial presentation does not predict the future
      development of cardiac metastasis. Taking an aggressive therapeutic approach,
      including thoracentesis, chemotherapy, and radiation therapy to the heart,
      survival and quality of life can be improved.

PMID- 9648601
TI  - Repeat Pap smear at the time of initial colposcopy--another view.

PMID- 9648602
TI  - [The effect of an NO-synthase inhibitor, methylene blue, on the function of
      certain endocrine glands].
AB  - Methylene blue is a thiazine dye, which has been used in the clinical medicine as
      disinfection agent and in treatment of methemoglobinemia. The recent
      investigations showed that this dye is able to inhibit the activation of
      guanylate cyclase pathway in the guanylate cyclase or in the NO-synthase level.
      This paper summarizes the experimentally obtained results concerning the
      influence of methylene blue on the hypothalamic, hypophyseal, thyroid and
      testicular function in rats. The possible mechanism of its influence with
      potential role of nitric oxide in the modulation of regulating pathways in these
      endocrine glands is discussed.

PMID- 9648603
TI  - [Biological effects of interacting shock waves. A modeling study of the effects
      of interacting shock waves using erythrocyte hemolysis].
AB  - AIM: The effects of high-energy shock wave on tissues were discussed in
      literature. The shock wave sources which were used for experiments were developed
      for stone fragmentation. The side effects of the applicators are generally low.
      Increase of shock wave pressure induce bigger negative pressure amplitude and
      this may cause significantly bigger side effects. We used tow shock waves, with
      time interval of 5 microseconds. In our opinion, the first shock wave causes
      acoustic inhomogenity in shock wave focus and therefore second shock wave acts in
      a region with different acoustic parameters. The second shock wave may loss
      energy in the focus area by dissipation or absorption. We termed the coupled
      shock waves as "interacting shock waves". METHODS AND RESULTS: Hemolysis of
      erythrocytes was used for examination of biological toxicity. Shock wave pressure
      was 80 MPa, the ratio of positive to negative pressure of single shock waves is
      30. For correlation we applied 50 and 100 single shock waves and 50 or 100
      couples of two shock waves. Hemolysis after 50 simple shock waves was 4.28 times
      lower compared with hemolysis after the same number of coupled shock waves
      (interacting shock waves). CONCLUSION: After 50 couples of shock waves hemolysis
      is 2.14 times higher compared with 100 single shock waves. This result suggests
      that the hypothesis of some interaction existing between two shocks applied in a
      very short time interval make future study rightful.

PMID- 9648604
TI  - [Voice prostheses mechanisms in total laryngectomy].
AB  - Loss of the voice after laryngectomy eliminates to a great extent patient's
      social life. Apart from other frequently used methods in laryngectomized
      patients, a number of tracheoesophageal vents called voice prostheses, has been
      developed in past decade. A survey of their most important features is given. A
      basic way of induction of these vents with technique of tracheoesophageal
      functions is described.

PMID- 9648605
TI  - [Voice rehabilitation with the Provox system after total laryngectomy].
AB  - Total laryngectomy has a profound impact on the life of a patient. The loss of
      the larynx creates a major communication problem that can result in disruption of
      the patients normal pattern of social interaction. It is for this reason that
      adaptation to the loss of normal speech has been the focus of research on the
      rehabilitation of laryngectomized patients. Tracheoesophageal puncture and
      induction of the voice prosthesis have very well results in rehabilitation of the
      voice. The long terms clinical results obtained by experience with any of the
      complication are described. We use 4 types of voice prosthesis (Provox, Blom
      Singer, Bivona Colorado and Czech prosthesis). We have very good experiences with
      system Provox. Our collection of the patients with Provox prostheses are 53
      patients after total laryngectomy. All tracheoesophageal punctures were done in
      second time. Over 85% patients were able to produce satisfying voice. Speech
      quality was evaluated by Robe scale. 38.9% of them can speak fluently, which
      corresponds with a category F. Local inflammatory reaction occurred in 28.1% that
      resulted in extrusion or removal of voice prostheses in 14.2% patients. Use of
      voice prostheses in rehabilitation of laryngectomized patients occupies a
      significant place.

PMID- 9648606
TI  - Erythrocyte sedimentation rate in glass and plastic pipettes.
AB  - In the blood collection practice there is a growing number of different closed
      systems. They often use plastic pipettes for testing the erythrocyte
      sedimentation rate (ESR) according to Westergren. Our previous experience with
      plastic pipettes as a part of the system Venoject II suggested that slightly
      higher values were obtained when compared to glass pipettes. In order to confirm
      these findings a special comparative trial was performed in a group of 302 blood
      samples. Statistical evaluation proved a significantly higher sedimentation rate
      in plastic pipettes. Based on the values from another group of 132 healthy adults
      we try to draw conclusions on the reference interval of ESR in plastic pipettes.
      We confirmed that no additional information can be derived from ESR values after
      two hours.

PMID- 9648607
TI  - [Empathy--understanding through identification].
AB  - Empathy is defined as an understanding of another individual through the
      projection of ones own personality. It is manifested by the willingness and
      effort to perceive, capture and understand the individuals both current and
      potential world as exactly as possible with all its subjective meanings and
      feelings. It is based on intuition attended by an emotional involvement and
      positive interest in the other person. The process of empathy runs in three
      stages which overlap: first we enter the other persons subjectivity, than share
      in his/her thoughts, emotions and feelings and finally comes the understanding of
      the other person. Empathy can be traced to phylogenesis, it is biologically
      anchored and in the course of human life (ontogenetic approach) it develops in
      the social milieu as do our other abilities. It is one of general effective
      factors of psychotherapy and, in the psychotherapeutic relationship, has both a
      direct and indirect effect upon the patient (within the hermeneutic process).
      Today, this matter is most extensively worked out by the Rogerian and
      psychoanalytic psychotherapy.

PMID- 9648608
TI  - [Research fraud].
AB  - In this article problems of research fraud are discussed. Academic courses of
      teaching scientific integrity and the impact of clinical trial fraud on good
      clinical research practice are mentioned.

PMID- 9648609
TI  - Multiprofessional education in social medicine and clinical ethics.
AB  - This contribution describes a project of multiprofessional education in social
      medicine and clinical ethics based on educational experience of 3rd Department of
      Internal Medicine, First Medical Faculty, Charles University in conjunction with
      the Centre of Gerontology Prague. This undergraduate program will be offered to
      medics, stomatologists and health science students including the English course
      and will invite to participate students from non-medical faculties such as social
      science, pedagogy, theology, interested in ethics of health care providing. Basic
      principles of the new project are: education in clinical setting, early student
      patient contact, multiprofessional education in common seminars of problem based
      learning small groups and developing various forms of communication.

PMID- 9648610
TI  - [Preparatory courses for applicants for medical studies].
AB  - From 1991, the First Medical Faculty of the Charles University arranges for
      applicants for the medical study two-semester preparatory courses paid by the
      applicants. Their purpose is to improve knowledge of high-school physics,
      chemistry and biology with orientation to model questions published by the
      faculty [1, 2, 3]. Variants of 100-questions sets for the examination are
      generated by a computer and they are altered every year [4]. Two types of
      preparatory courses are available. Type A--every Monday and Tuesday between 17.00
      and 18.45, physics and chemistry in odd weeks, biology and Latin in even weeks.
      Latin is not a discipline considered during the admission examination, however,
      managing of its basic knowledge facilitates not only understanding problems
      considered in the other disciplines, but it is particularly useful for learning
      the special terminology in the first year of the study of medicine. Course of
      type B is held once a month, on Saturdays between 8.30 and 14.00 and it is
      particularly designed for applicants residing beyond the capital city of Prague.
      In the course of 10 semesters implemented, 980 and 1,410 students passed through
      courses of type A and B, respectively [5, 6]. The purpose of our analysis was to
      evaluate the difference between results of admission procedure of applicants who
      participated and of those who did not participate in the preparatory course.
      Basic data were yielded by the Department of Students of the Deans Office. We
      considered the number of applicants, their results in the course of their four
      years of study at high schools and the number of points acquired in physical,
      chemical and biological tests. We furthermore obtained applications for
      preparatory courses in school years 1993/94 and 1994/95. The results were
      processed with the help of data base programs Access and Excel (Microsoft). In
      each of the years of interest, the applicants were divided into four groups
      depending on the type of the study: 1--medicine (L) and 2--stomatology (S) or
      depending on whether 3--they were registered in preparatory courses or 4--not.
      The analysis carried out resulted in the following conclusion: a--both groups of
      applicants (registered and not registered in preparatory courses) had comparable
      study results during the last four years of their high-school study; b--in the
      admission procedure, students, who passed through preparatory courses, achieved
      undoubtedly better results in comparison with those who did not pass through
      these course, which holds in medicine as well as stomatology; c--there was about
      the same improvement of knowledge of physics, chemistry and biology in both types
      of the preparatory courses.

PMID- 9648611
TI  - [The Prague school of anatomy and its illustrators].
AB  - The centennial commemorial of the birthday of Ladislav Borovansky gives us an
      incentive for describing a short history of Czech anatomy in Medical Faculty of
      Charles University with their textbooks and painters. Parallelly with them are
      presented some other distinguished painters active in anatomical aspect of
      illustration.

PMID- 9648612
TI  - [75 years' of the 2nd Clinic of Gynecology and Obstetrics of the 1st Medical
      School of Charles University and the General Medical School Hospital in Prague on
      the 120th anniversary of the opening of the Zemske Maternity Hospital].

PMID- 9648613
TI  - [Activity of the 2nd Clinic of Gynecology and Obstetrics from its founding to the
      end of World War II (1920-1945)].
AB  - History of the IInd Gynaecological and Obstetric Clinic of 1st Faculty of
      Medicine, Charles University in Prague is recorded here from its establishment in
      1920 to the end of World War II. The activities of the Clinic are depicted in
      characterization of prominent personalities who worked here in this period. The
      characterization is focussed mostly on head physicians and their clinical,
      pedagogical and scientific activities and their works published.

PMID- 9648614
TI  - [Recent history of the 2d Gynecology-Obstetrical Clinic of the 1st Medical School
      of Charles University (1945-1995)].
AB  - In 1995 75 years had elapsed since the time when the decision to found the Second
      Department of Obstetrics and Gynaecology was made by the Medical Faculty. An
      Institution arose which trained a great many qualified medical workers, midwives,
      students, and specialist obstetricians-gynaecologists. In the present article we
      should like to remember the teachers who have taken over the style of work from
      their predecessors and educated their pupils in the love and devotion to their
      discipline. In the last 50 years five Heads of the Department worked in the
      Second Department of Gynaecology and Obstetrics. Each of them made part of the
      history of the Department and imprinted there his or her characteristic image.
      Our wish is to acquaint you with the message of the predecessors as well as with
      the contemporary history and development of the Department in the field of
      education, research, and therapeutics.

PMID- 9648615
TI  - [Present status of the 2nd Gynecology-Obstetrical Clinic of the 1st Medical
      School of Charles University and the General Medical School Hospital in Prague].

PMID- 9648616
TI  - Jens Christian Skou awarded the Nobel prize in chemistry for the identification
      of the Na+, K(+)-pump.

PMID- 9648617
TI  - Potentiation of the contraction following a prolonged depolarization in isolated
      ferret myocardium.
AB  - The contractile force was studied in ferret papillary muscles during voltage
      clamp depolarizations, using the single sucrose gap method. Prolongation of a
      test depolarization within a train produced potentiation of the following
      contraction. The effects of varied duration and membrane potential of the test
      depolarization upon the potentiated force of the following beat were studied. We
      assumed that force of a beat was an index of calcium entry on the previous
      depolarization. The relationship between the peak contractile force of the
      following potentiated beat and the systolic membrane potential of the test
      depolarization revealed an equilibrium around -18 mV. This was manifest after 100
      ms of no effect. Positive potentials caused potentiation of force of the
      following beat; negative potentials caused suppression of force of the following
      beat. Calcium entry, if carried by an electrogenic exchange mechanism, would be
      revealed as a membrane current developing after 100 ms. Membrane current at these
      times was always outward. When the duration of the test depolarization was
      prolonged, outward current prior to repolarisation progressively increased. When
      the duration of the test depolarization was held constant, outward current was
      varied by variation in membrane potential. Force of the following beat was
      proportional to the test clamp membrane potential. The potentiation of the
      contraction following a prolonged depolarization was abolished by substituting
      75% of the sodium in the perfusion medium with lithium. These results are
      compatible with the hypothesis that potentiation of force following a prolonged
      depolarization is derived from calcium entry into myocardial cells by reversed
      sodium-calcium exchange.

PMID- 9648618
TI  - Effects of endurance training on the size and blood flow of the arterial
      conductance vessels in humans.
AB  - The aim of the present study was to determine non-invasively the effects of
      endurance training on both the size and blood flow of the arterial conductance
      vessels during exercise by men. Twelve healthy male subjects were assigned to
      either an exercise-trained group (ET, n = 7) or a sedentary control group (S, n =
      5). The ET group underwent cycle-endurance training for 8 weeks (80% VO2max, 40
      min day-1, 5 days week-1). The S group led normal lives during the 8-week period.
      Before and after the training period, cross-sectional areas (CSA) of the
      ascending and abdominal aorta were measured by echography. Measurements were
      taken in the semisupine position on a cycle ergometer fitted with a backrest, at
      rest and during 40, 60 and 80% VO2max of exercise. In addition, Doppler
      ultrasonographic velocity and flow in the ascending aorta were simultaneously
      measured. The CSA of the ascending and abdominal aorta after training were
      significantly larger than those before training in the ET group. Although there
      were no significant differences in the peak and mean velocities in the ascending
      aorta before and after the training in the ET group, the blood flow in the
      ascending aorta during exercise after training was significantly larger than that
      found before training at each relative intensity. There were no significant
      differences in any of the Doppler echographic parameters in the S group. These
      findings suggest that the arterial conductance vessels can be morphologically
      altered in an adaptive response to the endurance training. Furthermore, the
      dilation of the conductance vessels with endurance training contributes to an
      increase in blood flow to the exercising muscles without a rise in blood
      velocity. In other words, the arterial conductance vessels adapt to maintain
      adequate blood velocity and shear stress.

PMID- 9648619
TI  - Analysis of blood pressure responses during exercise by logistic function curve
      in hypertension: effects of age, gender and physical training.
AB  - During exercise blood pressure fluctuates from minute to minute and does not rise
      linearly with time. Blood pressure responses were evaluated during exercise by a
      logistic function curve. Thirty-nine hypertensive patients underwent exercise
      testing with an ergometer, employing a multistage method (25 watts increment,
      every 3 min). We plotted the exercise duration on the X-coordinate and systolic
      blood pressure on the Y-coordinate and blood pressure was assumed to form a
      logistic curve for exercise duration. The relationship of systolic blood pressure
      vs. exercise duration was better fitted into a logistic function curve than a
      linear regression model. The logistic curve was defined by lower plateau, upper
      plateau, SPX (the X-coordinate at the shift point) and df (SPX), the maximal
      slope at the shift point. The effects of aging, gender and physical training were
      then analyzed on the curve. Aging did not affect lower plateau, upper plateau and
      SPX but augmented df (SPX), indicating greater blood pressure responses in older
      subjects during exercise. In females the curve was shifted to the left compared
      to males (SPX: 4.9 vs. 8.3 min, P < 0.05) without changes in plateaux and df
      (SPX), indicating greater blood pressure responses than males. Physical training
      for 3 weeks decreased the lower plateau from 157 to 144 mmHg (P < 0.05) and
      shifted the curve to the right (SPX: 7.1 vs. 8.6 min, P < 0.05), indicating
      unchanged blood pressure responses after training because of the opposite effects
      by decreases in the lower plateau vs. the curve shift to the right. In
      conclusion, blood pressure during exercise is better delineated by a logistic
      function curve than a linear regression model. The biological or physiological
      significance of df (SPX) is not clear at present and needs further
      investigations.

PMID- 9648620
TI  - Effects of red blood cell hyperaggregation on the rat microcirculation blood
      flow.
AB  - This study presents the effects of red blood cell (RBC) hyperaggregation on the
      blood flow and pressure in the rat mesentery and cremaster network. We
      exclusively studied in situ non-vasodilated organs, in order to maintain the
      physiological regulation mechanisms. Dextran 500 was injected at different
      concentrations to increase RBC aggregation. The aggregation rate was measured on
      very small blood samples with an erythroaggregameter (SEFAM) which evaluated the
      disaggregating shear stress (tau D) needed to break the RBC aggregates.
      Microscopic observations and laser Doppler velocimetry were used to quantify the
      flow rate. The plasmatic dextran concentration (C) increase had different
      correlated effects: for example, tau D increased from 3 dynes cm-2 (for the
      control sample) to 14 dynes cm-2 (for C = 75 microM L-1); the flow rate was
      reduced threefold and very large aggregates were observed in the venules; the
      arteriolar pressure increased while venular pressure decreased. In order to
      differentiate the effects of RBC hyperaggregation from those of plasma
      hyperviscosity (due to dextran 500) on microcirculatory blood flow, we injected
      an RBC antiaggregating drug (troxerutine) (50 or 100 mg kg-1 i.v.). The
      consequences were a high reduction for (tau D) (from 14 dynes cm(-2)-9 dynes cm
      2), smaller aggregates and higher blood flow in the venules. No effect of
      troxerutine was observed on plasma viscosity (plasma control: 1.9 cP with or
      without troxerutine; plasma with dextran at C = 75 microM L-1: 2.45 cP with or
      without troxerutine). The results strongly suggest that RBC aggregation has a
      significant influence on blood flow rate in the microcirculatory network.

PMID- 9648621
TI  - Effects of age and gender on shortening velocity and myosin isoforms in single
      rat muscle fibres.
AB  - The maximum velocity of unloaded shortening (V0) and the myosin heavy chain
      (MyHC) and light chain (MyLC) isoform composition were determined in single
      fibres from soleus and extensor digitorum longus (EDL) muscles of male and female
      rate 3-6 and 22-24 months old. In the soleus muscle, the beta/slow (type I MyHC)
      isoform predominated in both young and old animals, irrespective of gender. In
      the EDL, fibres expressing type IIX MyHC or a combination of IIX and IIB (IIXB)
      MyHC isoforms were predominant in old rats, while type IIB MyHC fibres
      predominated in young individuals of both genders. The V0 of soleus fibres
      expressing the type I MyHC isoform decreased (P < 0.001) by 40% with age in spite
      of an unchanged MyLC composition. In the EDL, the V0 of fibres expressing IIX,
      IIXB and IIB MyHC isoforms did not changes with age or differ between males and
      females. In conclusion, similar age-related changes in V0 and MyHC composition
      were observed in single muscle cells from both male and female rats. The present
      results demonstrate that the relationship between V0 and MyHC isoform composition
      at the single fibre level is similar in male and female rats, and that similar
      qualitative changes take place during ageing in both genders.

PMID- 9648622
TI  - Influence of cold shivering on fine motor control in the upper limb.
AB  - The aim of the investigation was to determine the effects of cold shivering on
      the accuracy of force output in distal, middle and proximal muscles of the upper
      limb. Test of hand grip strength, elbow flexion and shoulder flexion (each done
      at 10% maximal voluntary contraction for 15 s) were done under three conditions:
      (1) thermoneutral air (27 degrees C), a condition of thermal comfort; (2) cold
      air (10 degrees C), a condition eliciting an increase in tonic muscle activity;
      (3) and cold air (10 degrees C) with a cold drink (8 degrees C), a condition that
      causes visible shivering. The averaged (root mean square) electromyogram (AEMG)
      and mean power frequency (MPF) were measured from proximal, middle and distal arm
      muscles during the tests and compared. The control of force output was highly
      effective at thermoneutral condition for all motor tasks. During the cold air
      condition, all muscles were tonically active but there was no effect on accuracy
      of test performance. However, AEMG increased approximately 20% (P < 0.05) with
      respect to test performance in thermoneutral condition. During the cold air/cold
      drink condition, all muscles were shivering to a different extend. AEMG during
      test performance increased 30-150% in comparison to thermoneutral condition (P <
      0.05). In this case, hand grip and elbow flexion were not adversely affected
      (these tests require middle and distal muscles) by cold shivering. However, the
      accuracy of performance of shoulder flexion was adversely affected. This is
      consistent with the fact that proximal muscles are more active during cold
      shivering.

PMID- 9648623
TI  - Effects of noradrenaline and flow on lactate uptake in the perfused rat hindlimb.
AB  - Skeletal muscle can release or take up lactate depending on the lactate
      concentration gradient across the cell membrane. In the perfused rat hindlimb
      without arterial lactate, both noradrenaline (NA) infusion and increased flow
      promote lactate release and oxygen consumption (VO2). However, it is unclear
      whether NA or increased flow rate have similar effects on lactate uptake. The
      present study compares these effects in the rat hindlimb perfused at a basal flow
      rate of 0.33 mL min-1 g-1 and 25 degrees C in the presence of added arterial
      lactate. When 10 mmol L-1 L-(+)-lactate was added to the arterial perfusate,
      lactate was taken up (16 +/- 1.0 mumol g-1 h-1, n = 13) by the hindlimb with a
      35% higher VO2 than that without added lactate. Doubling perfusion flow rate
      enhanced lactate uptake and VO2 by 120% and 40%, respectively. Glucose uptake was
      also increased (by 253%) with increased flow. Infusion of NA increased perfusion
      pressure, VO2 and glucose uptake similarly to those induced by increased flow
      rate. However, lactate uptake was inhibited by NA. This inhibition was not
      altered by the beta-adrenergic antagonist propranolol. Vasopressin also showed
      similar effects to NA to decrease lactate uptake associated with increased VO2
      and vasoconstriction. These data indicate that in the presence of a high arterial
      lactate concentration, NA has opposite effects from increased flow rate on
      skeletal muscle lactate uptake although both have similar effects on lactate
      release in the absence of arterial lactate. Inhibition of lactate uptake may
      relate to the vasoconstrictive action of NA.

PMID- 9648624
TI  - Inheritance of static and dynamic arm strength and some of its determinants.
AB  - Maximal static, eccentric and concentric torques and arm components estimated by
      anthropometry and measured by computed tomography were evaluated in 25 male
      monozygotic twins and 16 dizygotic twins (22.4 +/- 3.7 years). The importance of
      genetic and environmental factors in the observed variation in these measurements
      was estimated by genetic model-fitting techniques. In this sample of young adult
      male twins, genetic factors were significant in most of the strength
      measurements, arm muscle components and muscle activation variables. The
      contribution of genetic factors in strength measures depended on the angle,
      contraction type and to some extent on contraction velocity. For isometric
      strength, angle-specificity in genetic and environmental variation could be
      attributed to the degree of variability in muscle activation and performance
      discomfort at each specific angle, with the highest unique environmental impact
      at extreme angles. The high genetic contribution at 170 degrees, but not at 50
      degrees, possibly expressed different contributions of genetic factors in the
      muscle-length factor and moment arm in torques at both angles. The importance of
      genetic factors in eccentric arm flexor strength (62-82%) was larger than for
      concentric flexion (29-65%), as the pattern of genetic determination followed the
      torque-velocity curve. Genetic variations in contractile and elastic components,
      contributing differently to eccentric and concentric torques, together with
      velocity-dependent actin-myosin binding factors, could account for the observed
      differences. The broad heritability was very high for all anthropometric and arm
      cross-sectional area measurements (> 85%) and common environmental factors were
      only significant for anthropometrically estimated mid-arm muscle tissue are
      (48%). Heritability estimates of different arm muscularity measurements were
      comparable.

PMID- 9648625
TI  - Capsaicin can abolish spontaneous tone in guinea-pig trachealis.
AB  - The properties of spontaneous tone in isolated preparations of guinea-pig
      tracheal smooth muscle were examined. Experiments with control preparations
      revealed that 5-15 min after stretching the muscle with 0.15 mN, the spontaneous
      tone assumed a plateau value from which it declined gradually during the
      following hour. During the plateau, the force amounted to approximately 35% and 1
      h later to approximately 20% of a maximum KC1 contraction. The tone was
      independent of tetrodotoxin, atropine and propranolol. Indomethacin quickly and
      completely relaxed the tone in 15 of 21 preparations. However, four preparations
      retained some tone even after 1 h of treatment. Exposure to the C-fibre
      influencing drug capsaicin resulted in a dose-dependent, reversible suppression
      of spontaneous tone, normally preceded by a transient increase in force. No
      spontaneous tone at all remained after 1 h of 10 microM capsaicin. This effect
      was also found in preparations pretreated with tetrodotoxin, atropine and
      propranolol. Preparations, deprived of spontaneous tone by capsaicin-treatment,
      contracted distinctly when exposed to 10 microM arachidonic acid. This
      contraction was almost completely abolished by indomethacin, which indicates that
      the prostaglandin synthesis is functioning after capsaicin treatment and, thus,
      that inhibition of this synthesis is not responsible for the capsaicin effect.
      Exposure to phosphoramidon increased the spontaneous tone almost threefold.
      Addition of 3 nM neurokinin A in the permanent presence of capsaicin gave weaker
      contractions in preparations where prostaglandin synthesis had been abolished by
      indomethacin, as compared to contractions in preparations with intact
      prostaglandin synthesis. The data indicate that a continuous release of
      tachykinins from sensory C-fibres is essential for the generation of spontaneous
      tone and that a combination of tachykinins and prostaglandins determine the size
      of the tone in this preparation.

PMID- 9648626
TI  - Glomerular charge selectivity for horseradish peroxidase and albumin at low and
      normal ionic strengths.
AB  - The classical concept of a negative glomerular charge barrier has recently been
      questioned, mainly based on the somewhat high clearance for anionic horseradish
      peroxidase (HRP). The validity of using anionic HRP can be tested by changing the
      properties of the charge barrier. A rather unequivocal approach is to reduce the
      ionic composition of the perfusate and hence increase the Debye length. We
      determined the glomerular clearance for horseradish peroxidase and serum albumin,
      using isolated rat kidneys perfused at 8 degrees C to reduce the tubular
      modification of the primary urine. The perfusate contained trace amounts of the
      neutral 125I-nHRP and the anionic 131I-aHRP and were otherwise identical except
      for different ionic strengths, 152 mM and 34 mM, respectively. During control,
      the fractional clearance (theta) was 0.11 +/- 0.015 for nHRP and 0.045 +/- 0.010
      for aHRP, with an average clearance ratio (n/a) of 2.8 +/- 0.24. Low ionic
      strength reduced theta for aHRP to 0.027 +/- 0.006, giving an increased clearance
      ratio for HRP of 4.2 +/- 0.44. The existence of a negative charge barrier is
      supported by the experiments. The result obtained during normal perfusion is
      compatible with a charge density (omega) of 34 mEq L-1, using a model of
      homogeneously charged membrane. Low ionic strength perfusion reversibly reduced
      the concentration of fixed charges to 12 mEq L-1, suggesting an almost threefold
      increase of the glomerular membrane volume. Thus, the glomerular charge barrier
      should be regarded to have a dynamic gel structure rather than being a rigid
      membrane.

PMID- 9648627
TI  - Effects of receptor blockade on metabolism and renal actions of vasopressin in
      conscious dogs.
AB  - Vasopressin--but not the V2 receptor agonist [deamino-cis1,D-Arg8]-vasopressin
      (dDAVP)--may mediate natriuresis in dogs. The present study investigated this
      phenomenon by use of nonpeptide antagonists to V1a and V2 receptors 1-?1-[4-(3
      acetylaminopropoxy)benzoyl]-4-piperidyl?-3,4-dihydro-2 (1H)-quinolinone (OPC
      21268) and 5-dimethylamino-1-?4-(2-methylbenzoylamino)-benzoyl?-2,3,4,5-tetra
      hydro-1 H-benzazepine (OPC-31260), respectively) hypothesising that only V1a
      inhibition would reduce the natriuresis. In conscious dogs vasopressin secretion
      was suppressed by water loading (2% body weight) and replaced by infusion of
      vasopressin (50 pg min-1 kg-1) resulting in physiological plasma concentrations
      (plasma levels of AVP (pAVP) = 2.0 +/- 0.1 pg mL-1). In this setting, OPC-21268
      did not change the rate of sodium excretion. OPC-31260 increased water excretion
      12-fold without significant changes in sodium excretion. Heart rate, mean
      arterial blood pressure, glomerular filtration rate, and clearance of endogenous
      Li+ were unchanged. During vasopressin infusion, both antagonists increased pAVP,
      OPC-21268 by 20% and OPC-31260 by 100% (2.0 +/- 0.2-4.0 +/- 0.3 pg mL-1). In the
      absence of vasopressin infusion, OPC-31260 did not increase pAVP. Thus, the
      increase in pAVP appeared to be due to a decrease in metabolic clearance rate.
      The results indicate that the present dose of V1a receptor inhibitor OPC-21268
      does not reduce sodium excretion and that both vasopressin antagonists inhibit
      vasopressin metabolism.

PMID- 9648629
TI  - Regulation of porcine biliary secretion by secretin.
AB  - The importance of physiological plasma levels of secretin in biliary bicarbonate
      secretion is not known. However, in anaesthetized pigs the substantial hepatic
      output of bicarbonate into the duodenum in response to low doses of secretin
      exceeds pancreatic bicarbonate output. The aim was therefore to study the
      relationship between duodenal acidification, secretin and hepatic biliary
      bicarbonate output in the conscious pig. Gottingen minipigs (n = 22) were
      cholecystectomized and the common bile duct catheterized. The biliary bicarbonate
      secretion in response to intraduodenal HCl, secretin or pentagastrin given
      intravenously, and to meal was studied. Intraduodenal HCl infusion, secretin and
      pentagastrin given intravenously augmented hepatic bicarbonate output and plasma
      secretin concentrations significantly. The secretin response to acidification was
      sufficient to explain the subsequent increase in biliary bicarbonate secretion.
      Hepatic bicarbonate secretion and concentrations of CCK and secretin in plasma
      increased postprandially. Exclusion of bile salts from the duodenum abolished
      postprandial increase in bile volume and increased release of CCK in fasting and
      fed pigs whereas secretin release was diminished. The results demonstrate that
      hepatic bicarbonate secretion is stimulated by endogenous secretin and therefore
      may have a physiological role in duodenal neutralization.

PMID- 9648628
TI  - A2 adenosine receptors in Mongolian gerbil middle ear epithelium and their
      regulation of Cl- secretion.
AB  - The present study investigates the effects of adenosine and its analogues on Cl-
      secretion in primary cultures of gerbil middle ear epithelium. Short-circuit
      current (Isc), an index of transepithelial active transport, was measured on the
      same cells cultured on porous filters. Baseline Isc and transepithelial
      resistance were 27.0 +/- 0.7 microA cm-2 and 275 +/- 7 omega cm2, respectively (n
      = 178). Extracellular adenosine and its analogues elicited a sustained increase
      in Isc when added to apical or basolateral surfaces. Both the A2A selective
      agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamido adenosine and
      the A2A/A2B nonselective agonist 5'-(N-ethyl-carboxamido)adenosine (NECA)
      increased Isc, but NECA was more effective than CGS21680. A1 selective antagonist
      8-cyclopentyl-1,3-dipropylxanthine did not reduce NECA-induced Isc. These results
      suggest the presence of both A2A and A2B receptors. NECA did not stimulate a rise
      in the intracellular Ca2+ concentration ([Ca2+]i) in single middle ear epithelial
      cells cultured on glass coverslips. Dibutyryl cAMP (dbcAMP) induced an initial
      transient increase in Isc followed by the sustained plateau. Addition of dbcAMP
      also caused a transient increase in [Ca2+]i. The protein kinase A inhibitor, N-[2
      (p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide, greatly reduced the
      increase in the Isc responses to NECA. 1,2-Bis-(2-aminophenoxy)ethane N,N,N',N'
      tetraacetic acid-acetoxymethyl ester influenced neither the NECA-induced increase
      in Isc nor the dbcAMP-induced sustained phase of Isc, but greatly inhibited the
      dbcAMP-induced transient increase in Isc. Glibenclamide, a cystic fibrosis
      transmembrane conductance regulator (CFTR) channel inhibitor, reduced the NECA
      induced Isc. These results indicate that extracellular adenosine and its
      analogues activate the cAMP-protein kinase A system, but not intracellular Ca(2+)
      dependent mechanisms, leading to Cl- secretion, possibly through the CFTR Cl-
      channels in the cultured gerbil middle ear epithelium.

PMID- 9648630
TI  - Appearance of contractile endothelin-B receptors in rat mesenteric arterial
      segments following organ culture.
AB  - The aim of this study was to examine how different procedures for organ culture
      affect the expression of contractile endothelin(ET)-B receptors in a branch of
      the rat mesenteric artery. In fresh segments, ET-1 and ET-3 induced similar
      strong contractions, ET-1 being 20-fold more potent, whereas neither of the
      selective ETB receptor agonists, sarafotoxin 6c (S6c) nor IRL 1620, induced
      significant contractions. In segments cultured for 1 day, ET-3 was only 3-fold
      less potent as ET-1, and S6c and IRL 1620 induced concentration-dependent
      contractions which were about 60% of the ET-1 induced contraction. The maximum
      contractile response to S6c was not altered in segments cultured with foetal calf
      serum or in buffer solution, but was reduced to about 20% of the control value
      when cultured in glucose-free buffer solution. The contraction to S6c was
      abolished in segments placed in cold (4 degrees C) buffer solution. Removal of
      the endothelium had no effect on the S6c-induced contractions. Arteries cultured
      at isometric tension (at 2 mN) for 1 day achieved the same contractile response
      for ETB agonists as resting segments. Pressurized arteries (60 mmHg) did not
      constrict to S6c when mounted as a fresh segment but demonstrated a strong
      contraction after 1 day at this transmural pressure. This study suggests that the
      appearance of ETB receptor mediated contraction following organ culture is not
      dependent on specific nutrients, endothelial factors or absence of intrinsic
      tension, but is a metabolically active process.

PMID- 9648632
TI  - Intracellular calcium and electrical restitution in mammalian cardiac cells.
AB  - The role of calcium current and changes in intracellular calcium concentration
      ([Ca2+]i) in regulation of action potential duration (APD) during electrical
      restitution process was studied in mammalian ventricular preparations. Properly
      timed action potentials were recorded from multicellular preparations and
      isolated cardiomyocytes using conventional microelectrodes and EGTA-containing
      patch pipettes. APD increased monotonically in canine and guinea pig ventricular
      preparations with increasing diastolic interval (DI), while in rabbit papillary
      muscles the restitution process was biphasic: APD first lengthened, then
      shortened as the DI increased. When the restitution process was studied in single
      cardiomyocytes using EGTA-containing patch pipettes, the restitution pattern was
      similar in the three species studied. Similarly, no difference was observed in
      the recovery time constant of calcium current (/Ca-L) measured under these
      conditions in voltage clamped myocytes. Loading the myocytes with the [Ca2+]i
      chelator BAPTA-AM had adverse effects in rabbit and canine cells. In rabbit
      myocytes steady-state APD lengthened and the late shortening component of
      restitution was abolished in BAPTA-loaded cells. In canine myocytes BAPTA-load
      shortened steady-state APD markedly, and during restitution, APD decreased with
      increasing DI. The late shortening component of restitution, observed in
      untreated rabbit preparations, was greatly reduced after nifedipine treatment,
      but remained preserved in the presence of 4-aminopyridine or nicorandil. Beat to
      beat changes in APD, peak/Ca-L and [Ca2+]i, measured using the fluorescent dye,
      Fura-2, were monitored in rabbit ventricular myocytes after a 1-min period of
      rest. In these cells, the shortening of APD was accompanied by a gradual
      reduction of the peak/Ca-L and elevation of diastolic [Ca2+]i during the initial
      eight post-rest action potentials. It is concluded that elevation of [Ca2+]i
      shortens, while reduction of [Ca2+]i lengthens APD in rabbit, but not in canine
      ventricular myocytes. These differences may probably be related to different
      distributions of [Ca2+]i-dependent ion currents and/or to differences in calcium
      handling between the two species.

PMID- 9648631
TI  - The novel non-peptide selective endothelin A receptor antagonist LU 135,252
      protects against myocardial ischaemic and reperfusion injury in the pig.
AB  - The aim of the study was to investigate the efficacy of the novel non-peptide
      selective endothelin A (ETA) receptor antagonist LU 135,252 to limit the extent
      of myocardial ischaemic and reperfusion injury. Administration of LU 135,252 (1
      and 5 mg kg-1 i.v.) to anaesthetised pigs reduced mean arterial pressure (MAP)
      from 91 +/- 4 to 79 +/- 3 mmHg (P < 0.05) and 96 +/- 3-82 +/- 3 mmHg (P < 0.01),
      respectively. Heart rate, coronary blood flow and coronary vascular resistance
      were not affected by LU 135,252. The infarct size induced by 45-min ligation of
      the left anterior descending coronary artery (LAD) followed by 4-h reperfusion in
      pigs was 81 +/- 5% of the area at risk in control animals given vehicle (n = 8).
      In pigs receiving 1 mg kg-1 (n = 6) or 5 mg kg-1 (n = 8) of LU 135,252 i.v. 20
      min before ischaemia the infarct size was reduced to 64 +/- 3% (P < 0.05) and 35
      +/- 4% (P < 0.001), respectively, of the area at risk. During the reperfusion
      period there was a non-significant trend towards a higher coronary blood flow and
      a lower coronary vascular resistance in the groups given LU 135,252 compared to
      controls. Myocardial overflow of ET-like immunoreactivity was increased during
      the reperfusion period but it was not affected by administration of LU 135,252.
      It is concluded that administration of the selective ETA receptor antagonist LU
      135,252 effectively protects the myocardium from ischaemia/reperfusion injury,
      indicating that the ETA receptor subtype is involved in the development of
      ischaemia/reperfusion injury.

PMID- 9648633
TI  - Blood flow in the peritendinous space of the human Achilles tendon during
      exercise.
AB  - This study evaluated blood flow in the peritendinous space of the human Achilles
      tendon during rest and 40-min dynamical contraction of m. triceps surae. In 10
      healthy volunteers 133Xe was injected in to the peritendinous space just
      ventrally to the Achilles tendon 2 and 5 cm proximal to the calcaneal insertion
      of the tendon, respectively. Blood flow 5 cm proximal to the Achilles tendon
      insertion was found to increase 4-fold from rest to exercise whereas the exercise
      induced increase in blood flow was less pronounced, only 2.5-fold, when measured
      2 cm proximal to the Achilles tendon insertion. Lymph drainage from the area was
      found to be negligible both during rest and exercise. We conclude that dynamical
      calf muscle contractions result in increased peritendinous blood flow at the
      Achilles tendon in humans.

PMID- 9648634
TI  - Internal jugular venous spillover of noradrenaline and metabolites and their
      association with sympathetic nervous activity.
AB  - It is recognized that the brain plays a pivotal role in the maintenance of blood
      pressure and the control of myocardial function. By combining direct sampling of
      internal jugular venous blood with a noradrenaline isotope dilution method, for
      examining neuronal transmitter release, and microneurographic nerve recording, we
      were able to quantify the release of central nervous system noradrenaline and its
      metabolites and investigate their association with efferent sympathetic nervous
      outflow in healthy subjects and patients with pure autonomic failure. To further
      investigate the relationship between brain noradrenaline, sympathetic nervous
      activity and blood pressure regulation we examined brain catecholamine turnover,
      based on the internal jugular venous overflow of noradrenaline and its principal
      central nervous system metabolites, in response to a variety of pharmacological
      challenges. A substantial increase was seen in brain noradrenaline turnover
      following trimethaphan, presumably resulting from a compensatory response in
      sympathoexcitatory forebrain noradrenergic neurones in the face of interruption
      of sympathetic neural traffic and reduction in arterial blood pressure. In
      contrast, reduction in central nervous system noradrenaline turnover accompanied
      the blood pressure fall produced by intravenous clonidine administration, thus
      representing the blood pressure lowering action of the drug. Following
      vasodilatation elicited by intravenous adrenaline infusion, brain noradrenaline
      turnover increased in parallel with elevation in muscle sympathetic nervous
      activity. While it is difficult to assess the source of the noradrenaline and
      metabolites determined in our studies, available evidence implicates
      noradrenergic cell groups of the posterolateral hypothalamus, amygdala, the A5
      region and the locus coeruleus as being involved in the regulation of sympathetic
      outflow and autonomic cardiovascular control.

PMID- 9648635
TI  - Platelet serotonin transporter density and related parameters in endurance
      trained and sedentary male subjects.
AB  - A number of peripheral indices of serotonergic function were examined in
      endurance-trained (ET) and sedentary males using the blood platelet as a model of
      the serotonergic neurone. The aim of the study was to investigate possible
      involvement and adaptation of the central serotonergic system in exercise-induced
      fatigue. The [3H] paroxetine-defined density of platelet serotonin transporters,
      platelet serotonin content and the plasma concentration of amino acids were
      determined in 10 ET and eight sedentary males. The mean (standard deviation)
      density of the serotonin transporter in the platelet membranes of the ET subjects
      was greater [1237 (182) fmol mg protein-1] than that of the sedentary subjects
      [910 (119) fmol mg protein-1; P = 0.013]. No difference (P = 0.51) could be seen
      between the median (range) platelet serotonin content of the ET subjects [0.98
      (0.37-3.04) nmol platelet-10] and that of the sedentary subjects [0.82 (0.18
      1.49) nmol platelet-10]. The platelet poor plasma concentrations of tryptophan
      and tyrosine were lower in the ET subjects (P = 0.028 and 0.015, respectively).
      The present study suggests that the platelet membrane of the ET subjects has a
      greater density of the serotonin transporter and that this is inversely related
      to the circulating concentration of the serotonin precursor, tryptophan. It
      remains to be resolved whether the increase in serotonin transporter density in
      the platelet membrane of ET subjects is reflected centrally and whether the ET
      platelet population may be sufficiently different from that of sedentary
      individuals to alter serotonin transporter density.

PMID- 9648636
TI  - Myocardial interstitial noradrenaline monitoring during occlusion of inferior
      vena cava in cats.
AB  - To investigate myocardial interstitial noradrenaline (NA) kinetics during
      activation of systemic sympathetic nerves, we applied a dialysis technique to the
      left ventricle of anaesthetised cats and monitored myocardial interstitial NA
      levels during 6-min occlusion of the inferior vena cava (IVC). Dialysis probes
      were implanted in the left ventricular wall, and dialysate NA levels as an index
      of myocardial interstitial NA levels, were measured with high-performance liquid
      chromatographic-electrochemical detection. During IVC occlusion, dialysate NA
      levels progressively increased from 110 +/- 17 pmol L-1 in the control and
      reached 620 +/- 160 pmol L-1 at 4-6 min of IVC occlusion. Local administration of
      omega-conotoxin GVIA at 10 microM decreased the control dialysate NA level to 35
      +/- 0.2 pmol L-1. The IVC occlusion induced increase in dialysate NA was
      suppressed only at 0-2 min of IVC occlusion. Intravenous injection of omega
      conotoxin GVIA (10 micrograms kg-1) did not increase the dialysate NA levels
      during IVC occlusion. Local administration of desipramine at 100 microM increased
      the control dialysate NA level to 900 +/- 73 pmol L-1. The IVC occlusion induced
      progressive increase in dialysate NA was augmented at 2-6 min of IVC occlusion.
      These results suggest that the early increase in myocardial interstitial NA
      levels is mainly caused by neuronal release of NA from cardiac sympathetic nerve
      terminals, and that extraction from the circulation and neuronal NA uptake
      contribute to changes in myocardial interstitial NA levels after a delay of
      several minutes.

PMID- 9648637
TI  - Modulation of short latency stretch reflexes during human hopping.
AB  - To gain insight into central and peripheral reflex control mechanisms in moving
      humans we have investigated short latency stretch reflex activity in m. triceps
      surae during two legged hopping. The objectives were: (1) to compare movement
      induced short latency stretch reflexes in soleus and medial gastrocnemius (MG)
      muscles, (2) to determine the relationship between the size of these reflexes and
      the muscle spindle stretch velocities, and (3) to compare the size of the
      movement induced short latency stretch reflexes and the H-reflexes
      simultaneously. Six well-trained healthy male subjects participated and they
      hopped at three different work rates. Surface electromyogram (EMG) and H-reflexes
      were recorded during hopping. Muscle spindle length changes were estimated as the
      difference between estimated origin-to-insertion length changes and tendon length
      changes. The important findings were that during hopping: (1) movement induced
      short latency stretch reflexes were observed consistently in soleus, (2) the EMG
      amplitude of this stretch reflex was negatively correlated with the estimated
      peak muscle spindle stretch velocity (rs = -0.52, P < 0.02), and (3) the
      amplitude of the soleus H-reflex at touchdown did not change in parallel with the
      stretch reflex. The negative correlation observed between the stretch reflex and
      the estimated peak muscle spindle stretch velocity in soleus is opposite to the
      basic velocity sensitive behaviour of stretch reflexes mechanically elicited
      during resting conditions. Possible control mechanisms are discussed.
      Additionally, muscle spindle length changes estimated from changes in the
      skeletal movements (joint angles) should be inferred cautiously because of tendon
      compliance, especially at high tendon forces.

PMID- 9648638
TI  - Serotonin and neuroendocrine peptides influence DNA synthesis in rat and human
      small intestinal cells in vitro.
AB  - Animal studies suggest a mediator role for neuroendocrine peptides and amines in
      regulating cell proliferation in the gastrointestinal epithelium. Our aim was to
      examine the effect of serotonin and selected gastrointestinal peptides on DNA
      synthesis in a rat and human small intestinal cell line in vitro. IEC-6 and FHs
      74 cells were incubated with epidermal growth factor (EGF), insulin-like growth
      factor II, glucagon, substance P, neurokinin A, calcitonin gene-related peptide
      (GRP, CCGRP), neurotensin and serotonin. The cells were labelled with [methyl-3H]
      thymidine and processed for autoradiography. DNA synthesis was evaluated by the
      labelling index. Epidermal growth factor, insulin-like growth factor II,
      glucagon, and substance P increased the labelling index in a dose-related manner
      (P < 0.003). In contrast, a significant dose-dependent reduction of the labelling
      index was observed after administration of serotonin and neurokinin A (P <
      0.0001). Neurotensin and CGRP did not affect the labelling index. EGF, insulin
      like growth factor II, glucagon, substance P, serotonin and neurokinin A may be
      important physiological regulators of proliferation, of gastrointestinal cells.

PMID- 9648639
TI  - Isoform of Na+, K(+)-ATPase from rumen epithelium identified and quantified by
      immunochemical methods.
AB  - Using biopsies of rumen epithelium papillae a net influx of [86Rb+] was measured
      corresponding to a high concentration of Na+, K(+)-pumps found in [3H]ouabain
      binding studies (Kristensen et al. 1995). In the present study the Na+, K(+)
      ATPase in papillae homogenates is compared with purified (Na+, K+)-ATPase from
      different sources, immunochemically characterized with respect to the isoform of
      the hydrolytic alpha subunit and the concentration of pumps substantiated by a
      novel immunochemical method. Na+, K(+)-ATPase purified from bovine kidney was
      shown to contain one homogeneous high-affinity population of [3H]ouabain-binding
      sites (Kd 1.37 nM). The ouabain-binding capacity was 0.82 nmol (mg protein)-1.
      Site-directed polyclonal antibodies raised to isoform-specific sequences of the
      three known alpha-subunit isoforms and monoclonal alpha 1-specific antibodies
      were used for isoform characterization on western blots of peptides separated by
      SDS-polyacrylamide gel electrophoresis. All three isoforms were present in Na+,
      K(+)-ATPase prepared from bovine brain. The alpha isoform of bovine kidney Na+,
      K(+)-ATPase and of rumen epithelium homogenate appeared to be alpha 1 whereas
      alpha 2 and alpha 3 were undetectable. Using an alpha 1-specific antibody and
      125I-labelled antimouse IgG the content of (Na+, K+)-ATPase in rumen epithelium
      was determined by comparison of the signal from known amount of bovine kidney
      Na+, K(+)-ATPase on western blots. By this method rumen epithelium was found to
      contain 2.6 nmol Na+, K(+)-ATPase (g wet wt)-1, i.e. a similarly high or even
      higher concentration than previously seen in ouabain-binding studies on biopsies.

PMID- 9648640
TI  - Structure and individuality in psychoanalytic training: the Israeli controversial
      discussions.

PMID- 9648641
TI  - On loneliness, narcissism, and intimacy.
AB  - The complex interplay between narcissistic vulnerability, adolescent development,
      and the capacity for intimate relatedness is viewed here from the perspective of
      two distinct but interrelated experiential modes of Being and Doing. I offer a
      view of loneliness that begins with a critical reappraisal of the concept of
      narcissistic relatedness in association with difficulties in establishing
      intimacy. These difficulties are due to failures in the developmentally
      prescribed intimacy. These difficulties are due to failures in the
      developmentally prescribed integration of the experiential modalities of Being
      and Doing during the course of late adolescence and young adulthood. The type of
      loneliness encountered in adult life, its particular cast and subjectively
      experienced nature, are determined by the specific modality around which it has
      become primarily organized. Clinical material is presented to illustrate the
      meaning of loneliness in the presence of the object, and the paradoxical
      inability to be both with the object and without it.

PMID- 9648642
TI  - Narcissistic fragility in the process of befriending the unfamiliar.

PMID- 9648643
TI  - The emancipation of time from autistic encapsulation: a study in the use of
      countertransference.

PMID- 9648644
TI  - Two principles of functioning of the affects.

PMID- 9648645
TI  - Why Oedipus and not Christ?

PMID- 9648646
TI  - The detection of enzyme activity following sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis.
AB  - More than a hundred different enzymes impinging on aspects of cell function
      ranging from carbohydrate and lipid metabolism to signal transduction and gene
      expression to biomolecule degradation have been detected by the assay of their
      enzymatic activities following SDS-PAGE. The strategies by which this has been
      accomplished are as varied as the enzymes themselves and offer testimony to the
      creativeness and ingenuity of life scientists. Assay of enzyme activity following
      SDS-PAGE is well adapted to identifying the source of catalytic activity in a
      heterogeneous protein mixture or a heterooligomeric protein (20), or determining
      if multiple catalytic activities reside in a single polypeptide (60). The
      alliance of versatile enzyme assay techniques with the molecular resolution of
      SDS-PAGE offers a powerful means for meeting the increasing demand for the high
      throughput screening arising from protein engineering, combinatorial chemistry,
      and functional genomics.

PMID- 9648647
TI  - Preparation and characterization of an endogenously fluorescent annexin for
      detection of apoptotic cells.
AB  - Annexin proteins specifically bind anionic phospholipids such as
      phosphatidylserine, which are normally confined to the cytoplasmic leaflet of
      cellular membranes. During programmed cell death, or apoptosis, this phospholipid
      asymmetry is lost, and anionic phospholipids are exposed on the extracellular
      leaflet of the plasma membrane where they are accessible to exogenously added,
      labeled annexins. Chemically [e.g., fluoroscein isothiocyanate (FITC)]-modified
      annexin V has been widely used to detect and enumerate apoptotic cells by flow
      cytometry. We prepared chimeric proteins containing green fluorescent protein
      (GFP) fused to annexin V. A chimera containing GFP fused to the C-terminus of
      annexin V was soluble and fluorescent, but was unable to bind phospholipids. In
      contrast, a chimera containing GFP fused to the N-terminus of annexin V
      specifically bound apoptotic cells. GFP-annexin V represents a sensitive and
      facile alternative to FITC-annexin V for studies of apoptosis.

PMID- 9648648
TI  - Quantitative restriction fragment length polymorphism: a procedure for
      quantitation of diphtheria toxin gene CRM197 allele.
AB  - Here we present an assay for quantitation of a particular gene allele in DNA
      mixtures by means of restriction fragment length polymorphism (RFLP) in
      combination with polymerase chain reaction (PCR). We applied the quantitative
      RFLP principle for estimation of the relative amount of diphtheria toxin gene
      CRM197 allele in Corynebacterium diphtheriae culture DNA samples. The procedure
      is based on PCR-mediated generation of an artificial AluI restriction site
      specifically with the CRM197 DNA template. After AluI digestion of the PCR
      product and polyacrylamide gel electrophoresis of the restriction fragments, the
      percentage of CRM197 template in the initial DNA sample was determined by
      scanning a gel negative. The method was shown to give a linear response when
      applied to template mixtures containing different amounts of CRM197 reference
      template. For samples where non-CRM197 DNA was detected by AluI RFLP, we designed
      a further allele-specific PCR assay to determine whether the non-CRM197 template
      portion was the wild-type toxin gene allele.

PMID- 9648649
TI  - Detection of 8-oxoguanine in cellular DNA using 2,6-diamino-8-oxopurine as an
      internal standard for high-performance liquid chromatography with electrochemical
      detection.
AB  - The quantitative aspect of the electrochemical detection method to detect 8-oxo
      7,8-dihydroguanine (8-oxoGua) has been improved by using an internal standard. In
      addition, emphasis was placed on the reduction of artifactual oxidation of DNA
      during isolation and hydrolysis. Nuclear DNA was isolated from rat organs and
      purified on an anion-exchange column following treatment with proteinase K and
      RNase. DNA hydrolysis to nucleobases or nucleosides was performed using either
      formic acid treatment or enzymatic digestion, respectively. The levels of either
      8-oxoGua or 8-hydroxy-7,8-dihydro-2'-deoxyguanosine were comparable. For accurate
      quantification, 2,6-diamino-8-oxopurine [(NH2)2-OH-Pur], added prior to
      hydrolysis, was used as an internal standard for the high-performance liquid
      chromatography with electrochemical detection assay. The baseline level of 8
      oxoGua in DNA of Sprague-Dawley rats was estimated to be 2 to 5 8-oxoGua residues
      per 10(6) DNA bases, with slight differences depending on the tissue origin. In
      agreement with the results of previous observations, the level of the oxidized
      base in the kidney of animal treated with iron complexed to nitrilotriacetic acid
      (Fe-NTA) (15 mg/kg) was three- to fourfold higher than that of untreated rats or
      animals treated with a saline solution, while there was no change in 8-oxoGua
      levels in the liver and colon of these treated animals.

PMID- 9648650
TI  - Affinity purification of yeast cytochrome oxidase with biotinylated subunits 4,
      5, or 6.
AB  - Null mutants in COX4, COX5a, or COX6, which encode subunits 4, 5, and 6 of yeast
      cytochrome oxidase are blocked in assembly of the enzyme. The mutants are
      complemented by gene constructs expressing cytochrome oxidase subunits with a
      carboxyl terminal extension containing a biotinylation signal sequence. Spectra
      and enzyme activities of mitochondria from transformants expressing a
      biotinylated subunit indicate restoration of a functional cytochrome oxidase.
      Biotinylated cytochrome oxidase can be affinity-purified from mitochondrial
      extracts by fractionation on a monomeric avidin column. This method can be used
      to purify the enzyme from small amounts of starting material.

PMID- 9648651
TI  - Using light scattering to locate less than a microgram of protein per band in
      polyacrylamide tube gels after isoelectric focusing.
AB  - After separation by isoelectric focusing (IEF) or non-equilibrium pH gradient
      electrophoresis (NEPHGE) in 9.2 M urea polyacrylamide tube gels, proteins with Mr
      > 20,000 can be precipitated by shaking the gels in 25% methanol. When a fiber
      optic illuminator is placed in contact with the end of the gel, the cylindrical
      gel transmits light by internal reflection. In regions of the gel where protein
      is precipitated, this light is scattered, making it visible when the gel is
      viewed in a darkened room against a black background. The sensitivity of the
      method is moderate: less than 1 microgram protein per band (in a 3-mm diameter
      gel) can be detected. Because the protein in the bands precipitates rapidly (30
      min), the solution used (25% methanol) is fairly benign to proteins, and the
      apparatus is not expensive, this technique should be useful in several situations
      including electrophoretic purification schemes. This method is especially useful
      for evaluating the quality of an IEF or NEPHGE tube gel before using it for the
      second dimension of a two-dimensional gel.

PMID- 9648652
TI  - Study of NADH stability using ultraviolet-visible spectrophotometric analysis and
      factorial design.
AB  - The chemical stability of nicotinamide adenine dinucleotide coenzyme (NADH/NAD+)
      and its derivatives (NADPH/NADP+) was investigated using changes in the UV
      visible absorption spectra of these compounds. The spectra of cofactor (reduced
      form) were monitored at 340 nm wavelength in different buffers, showing a faster
      degradation in phosphate buffer. This was assigned to the adduct formation
      between phosphate and NADH (pyridine ring). The three-factor-two-level factorial
      design study evaluated the contributions: buffers (phosphate and Pipes 0.1 M),
      pH's (6.8 and 7.8), and temperature (25 and 30 degrees C). The freshly prepared
      aqueous solutions of coenzyme were analyzed after 40 min under the different
      conditions (eight assays in triplicate) of the experiment. The main observed
      effects of the NADH oxidation were, in increasing order, pH, temperature, and
      buffer without appreciable interactive effects. Therefore, it was verified that
      the better conditions for cofactor use were alkaline media employing Pipes buffer
      or its derivatives and low temperatures.

PMID- 9648653
TI  - An approach to predicting the stabilities of peptide nucleic acid:DNA duplexes.
AB  - An approach is described for predicting peptide nucleic acid (PNA):DNA duplex
      stability from base sequence by approximating the total free energy of
      dissociation, delta G degree tot, for these duplexes as the sum of five
      parameters: (a) a nearest-neighbor interaction summation term, sigma Nj delta G
      degree j; (b) an initiation term, delta G degree i; (c) a dangling-end
      stabilization term, delta G degree e; (d) a PNA:DNA stabilization term per
      nearest-neighbor interaction, delta G degree pna; and (e) an ionic strength term,
      delta G degree Na. Parameters (a) and (b) are approximated using previously
      determined values for DNA:DNA duplexes, whereas parameters (c), (d), and (e) are
      empirically determined. These terms are used to calculated delta G degree tot,
      which is used in conjunction with a transition enthalpy (delta H degree) value,
      also approximated from nearest-neighbor values previously derived for DNA:DNA
      duplexes, to calculate a melting temperature (Tm) for the PNA:DNA duplex.
      Predicted Tm values calculated by this approach agreed fairly well with measured
      values for 11 different PNA:DNA duplexes, as well as with literature values. The
      approach also accurately models ionic strength effects.

PMID- 9648654
TI  - Aggrecan immobilization onto polystyrene plates through electrostatic
      interactions with spermine.
AB  - A new procedure for the immobilization of proteoglycans and the core protein
      thereof via their carbohydrate chains onto enzyme-linked immunosorbent assay
      (ELISA) plate wells is presented. The aggrecan was immobilized via electrostatic
      interactions with spermine coupled to glutaraldehyde via Schiff's base, the
      latter being directly anchored onto ELISA wells. The amounts of aggrecan bound by
      this procedure measured immunochemically were 10-fold greater than those adsorbed
      by direct coating. The interaction of aggrecan and spermine may be inhibited by
      very small amounts of sulfated glycosaminoglycans or proteoglycans in a
      competitive manner, and therefore the system may be used for their quantitation.
      Bound aggrecan could react with link protein and therefore the system may be used
      for studying interactions of cartilage macromolecules. The method may also be
      used for direct quantitation of proteoglycans since the amounts adsorbed, in a
      given range of concentrations, are directly proportional to the amounts in
      solution.

PMID- 9648655
TI  - Determination of gene usage by differential polymerase chain reaction product
      hybridization.
AB  - All swine VH genes belong to a highly homologous family and have identical leader
      sequences, and the swine VH locus contains a single JH. The small number of VH
      genes used by the fetus and neonate in the first 6 weeks have unique CDR1 and
      CDR2 sequences, permitting each to be identified using specific oligonucleotide
      probes. We have used this system as a model for the development of a rapid method
      for determining the proportional usage of closely related genes based on
      differential polymerase chain reaction (PCR) product hybridization (DPPH). The
      validity of the method is demonstrated using mixtures of PCR product containing
      known amounts of VH gene DNAs and by comparing data obtained by this method with
      those obtained by enumeration of individual hybridizing clones from lymphoid
      tissue and peripheral blood B cells. Since DPPH is at least 100-fold more
      efficient than the enumeration of individual hybridizing clones, it is especially
      useful for analyzing large numbers of samples in population studies. The possible
      extension of this method to the usage of other genes is discussed.

PMID- 9648656
TI  - Temperature gradient chamber for relative growth rate analysis of yeast.
AB  - Relative growth is often used as a phenotypic measure to distinguish mutant and
      wild-type yeast or bacterial strains. Differential growth as a function of
      temperature is a convenient and accurate means of analyzing differences between
      strains. Slight differences in the genotypes of two strains frequently result in
      differential growth of the two strains as a function of temperature. We have
      developed a chamber for the simultaneous growth of multiple strains in microtiter
      plates along a temperature gradient. Image analysis was used to determine colony
      area and number at various times as a function of temperature. This chamber
      reduces the time required and increases the accuracy in measuring growth as a
      function of temperature. This occurs by allowing relative growth to be measured
      along a temperature gradient where all other conditions are constant. Two strains
      of yeast (Saccharomyces cerevisiae) with a known difference in temperature
      dependence of growth were used to demonstrate the performance of this chamber.

PMID- 9648657
TI  - Evaluation of taurine metabolism in cats by dual stable isotope analysis.
AB  - Taurine kinetics in cats was investigated using a bolus dose of [15N]- and [1,2
      13C2]taurine. The comparison of [15N]- and [13C2]taurine kinetics permitted an
      evaluation of the extent of taurine transamination. A methodology which involves
      N-pentafluorobenzoyl di-n-butylamine derivatization of taurine and GC/MS
      measurements of the 15N- and 13C-enrichments in cat urine was developed. Accuracy
      of the measurements was determined using pure standard compounds and the results
      showed that [13C2]taurine does not interfere with [15N]taurine. In cats, no
      differences were observed between both tracers. Therefore, we conclude that
      taurine reversible transamination does not occur at a significant level in cats.

PMID- 9648658
TI  - High-performance liquid chromatographic determination of insulin in rat and human
      plasma.
AB  - A rapid and simple isocratic chromatographic procedure for the determination of
      insulin in human and rat plasma using reversed-phase (RP) high-performance liquid
      chromatography with an ultraviolet/visible detector is described. The method
      includes extraction of insulin from human and rat plasma into dichloromethane,
      followed by back-extraction into 0.05 N hydrochloric acid. The organic phase was
      evaporated under a stream of nitrogen. The aqueous phase was filtered and a 100
      microliters aliquot was analyzed on a RP-C18 column eluted with a mobile phase
      consisting of a mixture of 74 vol of 0.2 M sodium sulfate anhydrous adjusted to
      pH 2.3 with phosphoric acid and 26 vol of acetonitrile. The flow rate was 1.2
      ml/min and the wavelength was set at 214 nm. The calibration curve was linear
      over the range of 75-800 microIU/ml. The precision of the assay expressed as
      coefficients of variation was less than 6% over the entire concentration range.
      The recovery for insulin ranged from 79 to 81% from human and rat plasma, with
      coefficients of variation less than 6%. The intra- and interassay coefficients of
      variation were less than 5.7%. The limit of detection was 50 microIU/ml.

PMID- 9648659
TI  - Immobilization of saccharides and peptides on 96-well microtiter plates coated
      with methyl vinyl ether-maleic anhydride copolymer.
AB  - We have previously reported a method to immobilize protein ligands on microtiter
      plates coated with methyl vinyl ether-maleic anhydride copolymer (MMAC) [Isosaki,
      K., et al. (1992) J. Chromatogr. 597, 123-128]. In this study, we improved the
      MMAC method to efficiently immobilize not only small ligands such as peptides and
      oligosaccharides, which could not be efficiently immobilized previously, but also
      heparin via its reducing end. Amino and hydrazino groups were introduced to MMAC
      coated microtiter plate wells by coupling to acid anhydride groups of MMAC with
      1,6-hexamethylenediamine and adipic acid dihydrazide, respectively. The amino
      groups introduced were allowed to react with peptides by use of divalent cross
      linkers. Hydrazino groups were allowed to react with formyl groups of saccharides
      by reductive amination. Peptides and oligosaccharides were immobilized in a dose
      dependent manner by these methods. In the case of the angiotensin peptide thus
      immobilized, the detection limit by monoclonal antibodies was as low as 0.1-1
      fmol peptide per well. Application of 20-200 nmol oligosaccharides to the well
      was sufficient to immobilize and subsequently detect lectins. Furthermore,
      heparin immobilized on the hydrazinocoated wells was successfully used for the
      binding assay of annexin IV.

PMID- 9648660
TI  - Detection and quantitation of 59Fe-labeled proteins using storage
      phosphorimaging.

PMID- 9648661
TI  - Cost- and time-efficient gel electrophoresis for mini-gel systems.

PMID- 9648662
TI  - Immuno- and gold staining of a single western blot.

PMID- 9648663
TI  - Enzymatic detection of ultraviolet-induced pyrimidine (6-4) pyrimidone
      photoproducts at nucleotide resolution in Saccharomyces cerevisiae.

PMID- 9648664
TI  - A new method for evaluation and dietary therapy of congenital: deficiencies of
      amino acid metabolic enzymes. Linear system analysis and optimization of feedback
      inputs for the metabolic pathways of lysine, methionine and isoleucine.
AB  - We intended to elucidate an integrated mathematical model of amino acid
      metabolism and we propose a system for optimization treatment of disturbed
      metabolic states caused by congenital enzyme deficiencies. Our analysis focused
      on the metabolic pathway starting at asparaginic acid proceeding to isoleucine,
      methionine and lysine. The rate of change in the concentration of the biochemical
      species was expressed as 21 linear rate equations. We obtained the rate constants
      and the magnitude of feedback from reported experimental data. Linear systems
      analysis revealed that the metabolic system under study was stable but
      uncontrollable. These properties were insensitive to changes in the magnitude of
      feedback. To show the effect of optimizing the feedback so that it minimizes the
      square of the concentration of the species and the control input, we analyzed the
      impulse response of the species, transient response and the singular value of the
      system for four cases; (1) at the physiological state without optimizing the
      feedback, (2) at the physiological state attained after optimizing the feedback,
      (3) at the pathophysiological state attained with enzyme deficiency states for
      lysine and methionine metabolism without optimizing the feedback, and (4) at the
      pathophysiological state attained after optimizing the feedback for enzyme
      deficiencies. In the enzyme deficient model, the impulse response oscillated and
      lasted longer than that in the physiological state. These changes appeared even
      in the species on other branched pathways. The singular value was elevated in the
      enzyme deficient state. By optimizing the feedback, all the impulse responses in
      the enzyme deficient state recovered to nearly those in the normal physiological
      state. Similarly, the transient response and the singular value in the enzyme
      deficient state recovered to nearly the normal physiological values. We
      elucidated the numerical value of the feedback gain for this optimization. The
      present analysis is useful for the evaluation of the integrated properties of
      amino acid metabolism and the optimization technique is potentially of use for
      determining a treatment course for congenital metabolic enzyme deficiencies.

PMID- 9648665
TI  - The synchronization of recruitment-based activities in ants.
AB  - A simple model of recruitment-based foraging in ants illustrates the idea that
      synchronized patterns of activity can endow a colony with the ability to forage
      more efficiently when a minimal number of active individuals is required to
      establish and maintain food source exploitation. This model, which can be
      extended to other activities that involve recruitment, may help explain why
      bursts of synchronization have been observed in several species of ants.

PMID- 9648666
TI  - Effect of environmental complexity on salt-adaptation in Sorghum bicolor.
AB  - Individual plants of Sorghum bicolor mature different adaptive reactions to
      salinity. The positive correlation between the frequency of specific reactions
      and the tolerance level of plants with that specific reaction results from
      adaptive determinism (AD). The effect of complexity in environmental conditions
      on AD in plants adapting for the first time to salinity, A0, and in their
      offspring A1 was compared. Environmental complexity increases when uncontrolled
      factors besides salinity affect plants. The diversity of reactions of plants
      correlates positively with environmental complexity. AD correlates negatively to
      environmental complexity in A1. In contrast, environmental complexity has no
      effect on AD in A0. A1 are more tolerant to salinity than A0: A1 inherited
      adaptive information. The likelihood that A1 plants are exposed to the same
      uncontrolled factor as their parent is low, and so the decrease of AD in A1 due
      to environmental complexity suggests that: (1) the information inherited is
      specific to saline conditions; (2) AD results mainly from inherited pre-existing
      information; plants react as informatively closed systems: saline conditions
      trigger the expression of an adaptive, pre-existing program. For A0, conclusions
      are: (1) the adaptive reaction is not an expression of pre-existing information;
      (2) AD emerges during the adaptation process: the environment imprints adaptively
      the plant's development. In this case, plants react as open systems in terms of
      information.

PMID- 9648667
TI  - Effects of feedback inhibition on transit time in a linear pathway of Michaelis
      Menten-type reactions.
AB  - An analysis of the effects of external and internal metabolites on the steady
      state behavior of linear pathways comprising a sequence of three Michaelis-Menten
      type reactions with and without a simple feedback inhibition (i.e. an interaction
      of an internal metabolite with the pathway) is performed with respect to the
      transit time tau by its formulation as rectangular-hyperbolic functions of the
      flux J, instead of direct expressions in terms of the external metabolite
      concentrations. For a given concentration of the external metabolite M1
      (substrate of the pathway) or M4 (product of the pathway), the flux J has a lower
      value in the pathway with feedback inhibition than in the pathway without
      feedback inhibition. With variation in the M1 concentration the transit time tau
      shows a concave relationship with the flux J which is virtually identical for
      both pathways, yielding a minimum at a certain value of J. With variation in the
      M4 concentration the transit time tau monotonously decreases with higher value of
      J, and for a given value of J the feedback inhibition allows a lower transit
      time. This effect is enhanced with stronger feedback inhibition, and is in turn
      greatly reduced with higher values of total concentration and rate constants for
      the first enzyme in the pathway.

PMID- 9648668
TI  - Second conference on foundations of information science: the quest for a unified
      theory of information.

PMID- 9648669
TI  - The informational perspective: an overview of the issue.
AB  - Papers arising out of the 1996 Conference on the Foundations of Information
      Science are introduced. A key motif is the continual violation and restoration of
      consistency, percolating and precipitating along vertical chains of informational
      objects.

PMID- 9648670
TI  - The cosmic environment for the growth of complexity.
AB  - The unifying scenario fo cosmic evolution is outlined by following the natural
      changes among radiation, matter and life in standard, big-bang cosmology. Using
      aspects of non equilibrium thermodynamics, especially energy flow considerations,
      we argue that it is the contrasting temporal behavior of various energy densities
      that have given rise to the environments needed for the emergence of galaxies,
      stars, planets, and life forms. We furthermore argue that a necessary (though
      perhaps not sufficient) condition--a veritable prime mover--for the emergence of
      such ordered structures of growing complexity is the expansion of the Universe
      itself. Neither demonstrably new science nor appeals to non-science are needed to
      explain the impressive hierarchy of generative change, from atoms to galaxies,
      from cells to society.

PMID- 9648671
TI  - Information loss in the continuum limit and Schrodinger's equation in an
      electromagnetic field.
AB  - Since the time of Einstein's work on Brownian motion it has been known that
      random walks provide a microscopic model for the diffusion equation. Less well
      known is the fact that some instances of Schrodinger's equation occur naturally
      in the description of the statistics of these same walks and thus have classical
      contexts which are distinct from their usual association with quantum mechanics.
      An interesting feature of these models is the fact that the information which
      relates Schrodinger's equation to its classical context is not contained in the
      partial differential equation itself, but is lost in the continuum limit which
      gives rise to the equation. In this article we illustrate the above by showing
      that Schrodinger's equation for a particle in an electromagnetic field in 1 + 1
      dimension occurs as a continuum limit of a description of a classical system of
      point particles on a lattice. The derivation shows that the information lost in
      the continuum limit is necessary to link the mathematics to the physical context
      of the equation.

PMID- 9648672
TI  - Quantum gravity and life.

PMID- 9648673
TI  - Dimensional symmetry breaking, information and fractal gravity in Cantorian
      space.
AB  - We derive the exact expectation value and standard deviation for the
      dimensionality of Cantorian spacetime. Connections to time symmetry breaking,
      information and the generalization of complex numbers are considered. Finally a
      link between general relativity and Cantorian spacetime is proposed which amounts
      to the claim that fractalization is the origin of gravity.

PMID- 9648674
TI  - Entropy and predictability of information carriers.
AB  - The structure of linear strings carrying information is investigated by means of
      entropy concepts. First conditional entropy and transinformation are introduced
      and several generalizations are discussed. The capability to describe the
      structure of information carriers as DNA, proteins, texts and musical strings is
      investigated. The relation between order and the predictability of informational
      strings is discussed. As examples we study the mutual information function of
      virus DNA and several long proteins. Further we show some (rather formal)
      analogies to the structure of texts, and strings generated by musical melodies.
      It is shown that several information carriers show long-range correlations.

PMID- 9648675
TI  - Dynamics of time and information in dynamic time.
AB  - Time is intrinsically locally asynchronous, dynamic in itself, and self
      organizing in having locally asynchronous time precipitate further asynchronous
      time while leaving behind globally synchronous time. The resulting global
      synchronism is skewed in locally asynchronous time, while being vertical to the
      effected globally synchronous time. Information is a dynamic attribute of time
      and can be represented as a skewed synchronism in locally asynchronous time.
      Information originates in the communication among asynchronous times of a local
      character.

PMID- 9648676
TI  - Information gain by endo-observers: chances and limitations.
AB  - Endo-observers can be described and classified on the basis of a novel two
      dimensional scheme. One axis stands for the observer's style of knowledge
      acquisition, whereas the other axis corresponds to the observer's style of
      knowledge representation. In this way several problems concerning the relation
      between the endo-observer and the exo-system can be studied more systematically.
      Among other things, it is shown that there are two complementarity relations
      which restrict the observer's capacity of information gain: a duality between
      structure and dynamics (an increased information gain on the structure of the
      endo-system implies a reduced information gain on its dynamics, and vice versa),
      and a duality between the predictive and the explanatory power of a model.
      Connections with the problem of hermeneutics are outlined.

PMID- 9648677
TI  - Exaptation and torsion: toward a theory of natural information processing.
AB  - Several conundrums are provoked by attempts to provide algorithmic descriptions
      of natural phenomena. A characteristic feature of natural computation is a
      breakdown in the formal simulation relation. This is called hermeneutic torsion,
      and is formally the failure to commute of a diagram describing homomorphisms
      between dynamical systems. This torsion is a source of computational power. For
      example, it is deeply involved with phenomena such as exaptation, wherein an
      existing structure is recruited for a novel function. Exaptation occurs
      continually at the macromolecular level and is fundamentally nonalgorithmic; our
      system-theoretic models of computation deal with structural descriptions for
      which a functional semantics must be assigned in advance, and a natural system
      continually 'diagonalizes out' of this semantics. This perspective clarifies the
      nature of computing power and encourages consideration of a new kind of
      transcomputational complexity.

PMID- 9648678
TI  - An information typology for understanding living systems.
AB  - It is argued that we can improve our understanding of living systems by focusing
      on their informational processes. Recent developments, primarily in evolutionary
      biology, cybernetics and systems theory, suggest that informational processes are
      of at least two, and probably three, different types; and that the interaction of
      these types can be seen as a basis for the self-construction of living systems.
      Following the work of Csanyi and Kampis, a distinction is drawn between
      referential and nonreferential information. This typology is further extended to
      include statereferential information. The statereferential type serves to lend
      stability to informational arrangements (organization) that are viable so that
      they may be propagated in space and time.

PMID- 9648679
TI  - Time, reflectivity and information processing in living systems: a sketch for the
      unified information paradigm in biology.
AB  - The recognition activity of biomacromolecules based on quantum non-demolition
      measurements is regarded as the basis of information processing. Reflective
      arrows in the set of mappings appearing from quantum measurements correspond to
      the Godel numbers created inside a system overcoming its incompleteness. Temporal
      evolution is a consequence of contradictory statements about the whole system in
      which a reflective arrow is both an element of the system and its signification.
      It results from the solution of a paradox in which the system generates new
      descriptions non-deducible from its previous states. The active combinatorial
      process of self modification of information, being an internalized language game,
      allows a system to create Godel numbers. The whole system is constructed
      according to percolating coherent events, providing 'vertical' self-assembly that
      is predetermined by the encoding and internal language games.

PMID- 9648680
TI  - Biological information and laws of nature.

PMID- 9648681
TI  - Dynamic information processing in natural and artificial olfactory systems.
AB  - A new strategy for building artificial gas sensing systems is suggested based on
      knowledge of the dynamic response mechanism of the olfactory system. Difficulties
      with the processing of time-dependent inputs by neural networks are discussed.

PMID- 9648682
TI  - The Feigenbaum scenario as a model of the limits of conscious information
      processing.
AB  - The Feigenbaum scenario of the mathematical period doubling sequence from order
      to deterministic chaos has led to new insights about the nonlinear dynamics of a
      wide variety of physical and biological systems. Multiple realms from purely
      mechanical systems, fluid dynamics and weather to the patterns of biological
      growth and the dynamic of the heart, hormone and brain rhythms have been found to
      exhibit aspects of the Feigenbaum period doubling sequence. We explore the
      possibility that the Feigenbaum scenario can be extended to experiences of
      sensation, perception and human cognition as well. We also review the empirical
      data that supports the view that the Feigenbaum scenario of the period doubling
      sequence may portray an important limit in conscious information processing. We
      conclude that a major function of consciousness may be to transform the
      nonlinear, irrational and difficult to predict dynamics of unconscious nature
      into the more linear, rational and predictable psychodynamics that make human
      experience and social life possible.

PMID- 9648683
TI  - Consciousness as a self-organizing process: an ecological perspective.
AB  - The evolution of consciousness is seen in the context of energy-driven evolution
      in general, where energy and information are understood as two sides of the same
      coin. From this perspective consciousness is viewed as an ecological system in
      which streams of cognitive, perceptual, and emotional information form a rich
      complex of interactions, analogous to the interactive metabolism of a living
      cell. The result is an organic, self-generating, or 'autopoietic', system,
      continuously in the act of creating itself. Evidence suggests that this process
      is chaotic, or at least chaotic-like, and capable of assuming a number of
      distinct states best understood as chaotic attractors.

PMID- 9648684
TI  - Conscious experience and information.
AB  - Conscious experience, our main source of information, has special properties.
      Primary among them is privacy, or privileged access by persons to their own
      conscious states. The consequent theoretical and practical problems for research
      on both consciousness and information are delineated.

PMID- 9648685
TI  - Social information: the person is the message.
AB  - Assumptions that Shannon's concepts cannot extend to social systems are
      challenged by showing that social information measures the reduced uncertainties
      individuals have about the systemic effects of each other's behavior. The
      'meaning' of individual actions is their collective consequences, which also
      measure reductions in systemic uncertainties about collective environments.
      Meaning is communicated through messages using media such as values, ethics and
      morals, which encourage individuals to act predictably and replicate the
      improbable behaviors characterizing particular societies. When individuals
      internalize meaning, their personal identities communicate societal priorities to
      future generations.

PMID- 9648686
TI  - Information and the unfolding of social life: molecular-biological resonances
      reaching up to the economy.
AB  - The much vexed analogy between cells, organisms, and societies receives a new
      treatment here. It is argued that, based on an enlarged view on the relationship
      between information and life, one can approach economy from an unusual angle: the
      accounting processes that take place in every productive unit and commercial
      organization. Such accounting processes have been historically developed in order
      to coordinate the economic 'physiology' of complex societies. In this sense, the
      convergence which can be found amongst the abstract, coordinating operations
      performed by cellular signaling systems, vertebrate nervous systems, and
      entrepreneurial accounting systems appears as a relevant theoretical item to
      analyze (the abstract organization of what can be called information 'phase
      transitions'). Its development lends support to the cogency of a 'vertical'
      information science approach.

PMID- 9648687
TI  - Dynamics and information processing in adaptive systems.
AB  - An adaptive system is capable of functioning despite some degree of environmental
      uncertainty. This requires an ability to identify relevant states of the
      environment, to adjust the value of internal variables so as to maintain a
      characteristic pattern of activity and, of course, to respond appropriately to
      environmental stimuli. Biological systems have responded to this challenge by
      developing information processing systems that are highly compatible with their
      functions. In this paper we analyze the relationship between dynamics and
      information processing in biological systems and refer to basic principles of
      biological information processing. An important trend that can be observed is
      that the specialization of information processing functions increases with the
      complexity of the environment faced by the systems. At the level of human
      populations, man-made organizations in particular, our study suggests that the
      design of computer-based information systems must be sensitive to the existing
      biological infrastructure if they are to effectively extend the cognitive and
      computational capabilities of organizations.

PMID- 9648688
TI  - Soft mathematics and information dynamics.
AB  - We present a brief overview of a new framework for interdisciplinary
      collaboration toward understanding the fundamentals of information dynamics in
      social systems. The need for a new mathematics is noted, and a promising
      component, soft mathematics, is described.

PMID- 9648689
TI  - Information and third order ontology.
AB  - The question of 'a unified theory of information' is addressed from the logical
      position of many-valued ontologies. Information is described as an operational
      factor which forms a trans-contextural bridge between disjunct ontological
      systems (or monocontextures).

PMID- 9648690
TI  - Ontological measurement.
AB  - Endophysics ultimately deduces an indefinite interface between an object and an
      observer. Objects, given such an interface, cannot be distinguished from the
      measurement process used to identify them. Evolutionary processes comprising of
      emergent properties and adaptability are seen in a new light. The concept of
      indefiniteness and/or paradox appears on the surface to be based on the
      epistemological framework of the Cartesian cut. However, perpetual processes
      consisting of generation and resolution of paradoxes are beyond the
      epistemological framework of measurement. They lead to the notion of progression,
      which one can refer to as ontological (or inherent) measurement.

PMID- 9648691
TI  - Cybersemiotics: a transdisciplinary framework for information studies.
AB  - This paper summarizes recent attempts by this author to create a
      transdisciplinary, non-Cartesian and non-reductionistic framework for information
      studies in natural, social, and technological systems. To confront, in a
      scientific way, the problems of modern information technology where
      phenomenological man is dealing with socially constructed texts in
      algorithmically based digital bit-machines we need a theoretical framework
      spanning from physics over biology and technological design to phenomenological
      and social production of signification and meaning. I am working with such
      pragmatic theories as second order cybernetics (coupled with autopolesis theory),
      Lakoffs biologically oriented cognitive semantics, Peirce's triadic semiotics,
      and Wittgenstein's pragmatic language game theory. A coherent synthesis of these
      theories is what the cybersemiotic framework attempts to accomplish.

PMID- 9648692
TI  - The emerging global community.
AB  - Human society may be viewed as an evolving system. From time to time, there
      occurs the equivalent of a phase shift, or more appropriately, a 'cultural
      discontinuity'. In each case, such a discontinuity is preceded by, and caused by
      the emergence of a constellation of new technologies. During and following such a
      discontinuity previously existing cultural institutions become modified, or
      abolished all together, while new ones arise. The paper considers the impact of
      the Industrial and the Electronic revolutions on absolute monarchy, slavery, the
      State, war, and the emergence of an integrated global community.

PMID- 9648693
TI  - The making of the information society: driving forces, 'Leitbilder' and the
      imperative for survival.
AB  - In the field of science-technology-society, there are three one-sided approaches
      to analyzing the spread of the Internet: technology-push, economy-pull, and
      community-pull. Information science, when dealing with the transformation of our
      societies, will have to cover all of them and even try to find out missing links.
      We propose adding the analysis of metaphors accompanying the introduction and
      diffusion of new technologies, and evaluating metaphors and technologies using
      the criterion of how well they are shaped to meet global challenges. We conclude
      that contrary to ideological promises the capability of society to generate
      survival-relevant information will not be improved by establishing the so-called
      data highway per se, unless additional requirements are met which refer to higher
      information levels of knowledge and wisdom.

PMID- 9648694
TI  - Webometry: measuring the synergy of the World-Wide Web.
AB  - This is the second progress report on the webometry project: acquisition of data
      regarding the density of links on the world-wide web (WWW). We illustrate the
      primary visualization strategy, the synergy matrix, in the case of a model subnet
      of nine nodes.

PMID- 9648695
TI  - The relativist stance.
AB  - The two mindsets of absolutism and relativism are juxtaposed, and the relational
      or relativist stance is vindicated. The only 'absolute' entity which undeniably
      exists, consciousness has the reality of a dream. The escape hatch from this
      prison is relational, as Descartes and Levinas found out: Unfalsified relational
      consistency implies exteriority. Exteriority implies infinite power which in turn
      makes compassion inevitable. Aside from ethics as a royal way to enlightenment, a
      new technology called 'deep technology' may be accessible. It changes the whole
      world in a demonstrable fashion by manipulation of the micro frame--that is, the
      observer-world interface.

PMID- 9648696
TI  - Occupational asthma caused by tetrachlorophthalic anhydride: a 12-year follow-up.

PMID- 9648697
TI  - Indoor allergens and longitudinal FEV1 decline in older adults: the Normative
      Aging Study.
AB  - We investigated the relationship between home allergen exposure and decline in
      FEV1 in 10 asthmatic and 30 randomly selected, age-matched, nonasthmatic
      participants in the Normative Aging Study. We defined asthma as subject-reported
      wheezing apart from colds, with either a physician's diagnosis of asthma or a
      methacholine PD20 FEV1 of 8.6 micromol or less. We examined the relationship
      between the annual decline in FEV1 and the concentrations of the cockroach
      (Blattella germanica) allergens Bla g 1 and Bla g 2, the dust mite
      (Dermatophagoides pteronyssinus and Dermatophagoides farinae) allergens Der p 1
      and Der f 1, and the cat (Felis domesticus) allergen Fel d 1 in house dust
      specimens. Bla g 1 (-79.8 ml/yr, p = 0.0006) and Bla g 2 (-40.81 ml/yr, p =
      0.0004) were significant predictors of decline in FEV1 after adjustment for age,
      smoking, and baseline FEV1. These results were unchanged after elimination of the
      asthmatic subjects from the analysis. We conclude that cockroach allergen levels
      in homes is a risk factor for accelerated decline in FEV1 independent of airway
      responsiveness.

PMID- 9648698
TI  - The common cold: effects of intranasal fluticasone propionate treatment.
AB  - OBJECTIVE: A double-blind, randomized, placebo-controlled trial was conducted to
      study the effect of the intranasal corticosteroid, fluticasone propionate (FP),
      in the naturally occurring common cold. METHODS: One hundred ninety-nine young
      adults received high-dose FP (200 microg four times daily) or placebo beginning
      24 to 48 hours after onset of the common cold for 6 days. All symptoms were
      recorded on diary cards on days 1 to 20, and clinical examinations were carried
      out on days 1, 7, and 21. Nasopharyngeal aspirates were collected on days 1 and 7
      for detection of rhinoviruses (found in 105 subjects) and Streptococcus
      pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis (found in 52
      subjects) in the nasopharynx. RESULTS: In general, FP treatment had no clinically
      recognizable effects on the symptoms of the common cold, although it
      significantly reduced nasal congestion and cough on some study days. After
      treatment, rhinoviruses were cultured more often in the FP treatment group (37%
      vs 14%, p < 0.001), but this had no effect on the symptoms of common cold. FP
      treatment produced no changes in the colonization of pathogenic bacteria in the
      nasopharynx. Some symptoms of common cold were significantly more severe during
      days 1 to 10 (p < 0.05) in subjects found to have positive cultures for S.
      pneumoniae, H. influenzae, or M. catarrhalis in the nasopharynx on day 1 (n =
      33). CONCLUSION: FP treatment does not have any marked effects on the symptoms of
      the common cold. FP treatment induced prolonged shedding of viable rhinoviruses.
      Some symptoms of the common cold were significantly more severe in subjects with
      pathogenic bacteria in the nasopharynx.

PMID- 9648699
TI  - Subjects with seasonal allergic rhinitis and nonrhinitic subjects react
      differentially to nasal provocation with chlorine gas.
AB  - BACKGROUND: Nasal irritation and associated symptoms (nasal congestion,
      rhinorrhea, and sinus headache) are important elements of the response to indoor
      and outdoor air pollution. Marked interindividual variability in such symptoms
      has been suggested clinically and epidemiologically, but little experimental data
      exist on this issue. OBJECTIVE: We sought to test the hypothesis that subjects
      with seasonal allergic rhinitis (SAR) exhibit a more marked physiologic response
      (congestion) after nasal irritant provocation than do nonrhinitic subjects.
      METHODS: We studied eight subjects with SAR and eight nonrhinitic subjects;
      subjects with SAR were studied out of season. In a single-blind crossover study,
      subjects had their nasal airway resistance (NAR) measured in triplicate before,
      immediately after, and 15 minutes after a 15-minute exposure to either filtered
      air or 0.5 ppm chlorine in filtered air, administered through a nasal mask in a
      climate-controlled chamber. Log-transformed NAR values were analyzed in a
      repeated-measures analysis of variance model, with confirmatory testing using
      paired t tests. RESULTS: The net (chlorine minus air day) percent change in NAR
      from baseline (before exposure) to immediately after exposure was +24% in the SAR
      group and +3% in the nonrhinitic group (p < 0.05). The corresponding net changes
      from baseline to 15 minutes after exposure were +21% in the SAR group and -1% in
      the nonrhinitic group (p < 0.05). CONCLUSIONS: The observed augmented nasal
      congestive response of subjects with SAR versus nonrhinitic subjects to a
      controlled low-level chemical irritant provocation is consistent with
      epidemiologic surveys showing a higher prevalence of nasal symptoms among
      subjects with SAR than nonrhinitic subjects in environments involving irritant
      air pollutants.

PMID- 9648700
TI  - Latex allergy and latex sensitization in children and adolescents with
      meningomyelocele.
AB  - BACKGROUND: The high prevalence of clinical latex allergy and latex sensitization
      in children with meningomyelocele has been widely reported. It has also been
      noted that these same children have a higher than expected prevalence of atopic
      disease. It would be useful to have a safe, sensitive, and specific skin test to
      detect latex sensitivity and to know how well this test compares with available
      in vitro tests. It would likewise be helpful to know as fully as possible the
      characteristics of the individual and to evaluate the relative importance of
      factors suspected to contribute to clinical latex allergy and latex sensitization
      in this population. METHODS: A group of 116 children and adolescents 1 to 20
      years of age were recruited for the study. An extensive history of latex allergy,
      atopic diseases, and surgical procedures was taken on all subjects. Each subject
      had either a latex skin test or an in vitro study for latex-specific IgE, and 67
      subjects had both tests simultaneously. Eighty-five subjects had epicutaneous
      skin tests to a panel of environmental allergens. RESULTS: Overall, 25 of 116
      (21.5%) subjects had a history of clinical latex allergy, and 51 of 116 (44%)
      were sensitized to latex. The sensitivity and specificity of skin tests for
      clinical latex allergy were slightly greater than for the in vitro test (100% vs
      95.8% and 82.3% vs 68.9%, respectively). The positive predictive value and
      negative predictive value of skin testing for clinical latex allergy were also
      greater (67.6% vs 50% and 100% vs 98.1%, respectively). Age was found to be a
      significant variable for both latex allergy and latex sensitization. The number
      of surgical procedures undergone and the presence of positive skin test responses
      to environmental allergens were significantly correlated with latex sensitization
      but not with clinical allergy to latex. CONCLUSIONS: A sensitive, specific, and
      safe skin test for latex sensitivity appears superior to in vitro testing for
      latex allergy. Age, number of surgical procedures, and the presence of positive
      allergen skin test responses are significantly correlated with latex
      sensitization. Age alone is significantly correlated with clinical allergy to
      latex.

PMID- 9648701
TI  - Successful immunotherapy with T-cell epitope peptides of bee venom phospholipase
      A2 induces specific T-cell anergy in patients allergic to bee venom.
AB  - BACKGROUND: Specific immunotherapy with honeybee venom (BV) is highly effective,
      but allergic side effects can occur during treatment. Immunotherapy with peptides
      containing major T-cell epitopes of the relevant allergen or allergens provides
      an alternative strategy without these problems. OBJECTIVE: The study investigates
      the immunologic mechanisms and clinical effects of immunotherapy with T-cell
      epitope peptides of the major BV allergen, the phospholipase A2 (PLA). METHODS:
      Five patients with IgE-mediated systemic allergic reactions to bee stings were
      treated with a mixture of three T-cell epitope peptides of PLA. Ten patients
      allergic to BV receiving whole BV immunotherapy served as control subjects.
      Increasing doses of the peptide mixture, up to a maintenance dose of 100 microg,
      were administered subcutaneously within 2 months. The patients were then
      challenged with PLA and 1 week later with a bee sting. The cellular and humoral
      immune response was measured in vitro. RESULTS: No allergic side effects were
      caused by the peptide immunotherapy, and all patients tolerated the challenge
      with PLA without systemic allergic symptoms. Two patients developed mild systemic
      allergic reactions after the bee sting challenge. After peptide immunotherapy,
      specific proliferative responses to PLA and the peptides in peripheral blood
      mononuclear cells were decreased in successfully treated patients. The production
      of TH2 and TH1 cytokines was inhibited, and B cells were not affected in their
      capacity to produce specific IgE and IgG4 antibodies. Their levels increased
      after allergen challenge in favor of IgG4. CONCLUSIONS: Immunotherapy of BV
      allergy with short T-cell peptides of PLA induces epitope-specific anergy in
      peripheral T cells and changes the specific isotype ratio in a fashion similar to
      that of conventional immunotherapy in successfully treated patients.

PMID- 9648702
TI  - Juniperus oxycedrus: a new allergenic pollen from the Cupressaceae family.
AB  - BACKGROUND: Cupressaceae allergy is a worldwide pollinosis caused by several
      species. Some species in limited geographic areas pollinate in fall and winter.
      Juniperus oxycedrus matches these features. OBJECTIVE: We sought to define the
      immunochemical, allergologic, and environmental aspects of J. oxycedrus pollen.
      METHODS: Pollen extract from J. oxycedrus was prepared and characterized by
      biochemical analysis and human specific IgE binding by means of ELISA and
      immunoblotting. A 3-year phenological study was conducted to define the
      pollinating period of J. oxycedrus. Forty consecutive patients allergic to
      cypress were recruited in two areas and divided into two groups according to
      their exposure to J. oxycedrus pollen. Clinical evaluation, skin prick tests, and
      specific IgE determination with J. oxycedrus, J. ashei, and Cupressus arizonica
      extracts were carried out on both groups. RESULTS: J. oxycedrus pollen extract
      was obtained, and it showed specific IgE binding and wide cross-reactivity with
      other Cupressaceae species. The extract caused a positive skin test response in
      all the patients tested, with about 80% of them having detectable specific IgE.
      Symptoms related to J. oxycedrus pollen exposure were recorded in 72% of the
      directly exposed patients and occasionally in 9% of the nonexposed patients. In
      the Mediterranean coastal area considered, J. oxycedrus was the first
      Cupressaceae species that started to pollinate at the beginning of November and
      ended in the first part of December. CONCLUSIONS: J. oxycedrus represents a newly
      characterized pollen species of the Cupressaceae family that cross-reacts with
      other members of the same family. Subjects with cypress allergy have in vivo and
      in vitro positive test responses for J. oxycedrus and can show symptoms when
      exposed to its pollen. Finally, the most important feature of J. oxycedrus is its
      early pollinating period in southern Europe (Italy), causing a further extension
      of the cypress pollen season in areas where other Cupressaceae species are
      present.

PMID- 9648703
TI  - The effects of monosodium glutamate in adults with asthma who perceive themselves
      to be monosodium glutamate-intolerant.
AB  - BACKGROUND: Many previous clinical studies of food-induced asthma suffer from
      inadequate baseline or control data. A statistically valid, randomized, double
      blind, placebo-controlled, monosodium glutamate (MSG)-challenge protocol was
      developed for identifying early and late asthmatic reactions in an individual.
      OBJECTIVE: We sought to determine whether MSG would induce bronchoconstriction in
      a group of adults with asthma who perceived that they were MSG sensitive.
      METHODS: Twelve subjects (seven women, mean age 35.3 years) with clinically
      documented asthma and a perception of MSG-induced asthma were recruited. FEV1 and
      peak expiratory flow data were obtained for 3 whole control days, as well as time
      matched data for 3 separate challenge days (1 gm MSG, 5 gm MSG, and 5 gm lactose
      [placebo]). Opaque capsule challenges were given as a single dose in the morning
      after an overnight fast. Subjects complied with an elimination diet throughout
      the study. Nonspecific bronchial hyperresponsiveness was measured at baseline,
      after the control days, and at the conclusion of the challenges. Venous blood
      samples were taken at baseline and on each challenge day to determine soluble
      inflammatory marker (eosinophil cationic protein and tryptase) activity. RESULTS:
      No immediate or definite late asthmatic reactions occurred. One subject's FEV1
      declined more than 15% on MSG challenge, but 95% confidence limits for the
      control-day spirometry showed that this decline was within her daily variation,
      hence the challenge was deemed to be negative. No significant changes in
      bronchial hyperresponsiveness or soluble inflammatory markers were found.
      CONCLUSIONS: MSG-induced asthma was not demonstrated in this study. This study
      highlighted the importance of adequate baseline and control data and indicated
      that such a rigorous protocol for individual assessment is feasible.

PMID- 9648704
TI  - Molecular characterization of a cross-reactive Juniperus oxycedrus pollen
      allergen, Jun o 2: a novel calcium-binding allergen.
AB  - BACKGROUND: Species belonging to the Cupressaceae family are a relevant source of
      allergens that are present in a wide number of countries. OBJECTIVE: We sought to
      identify, purify, and characterize recombinant allergens from Juniperus
      oxycedrus, a species belonging to the Cupressaceae family. METHODS: Double
      stranded cDNA was synthesized from mRNA and cloned into the lambda-ZAP expression
      vector. IgE screening of the library was performed with a pool of sera from
      subjects allergic to Cupressaceae. A recombinant 6xHis-tagged Juniperus oxycedrus
      allergen, Jun o 2, was expressed in Escherichia coli and purified by Ni2+
      affinity chromatography. It was studied further by immunoblotting inhibition with
      pollen extracts from other Cupressaceae, Oleaceae, Urticaceae, and Graminaceae.
      The role of protein-bound calcium on the allergen's IgE-binding capacity was
      tested in a plaque assay in the presence or absence of EGTA. RESULTS: A cDNA
      coding for a newly identified Juniperus oxycedrus pollen allergen, rJun o 2, was
      isolated. The deduced amino acid sequence contained four typical Ca2+ binding
      sites and showed a significant sequence similarity to calmodulins. Depletion of
      Ca2+ in the plaque assay led to a loss of IgE-binding capacity of rJun o 2.
      Immunoblotting inhibition revealed that J. oxycedrus, J. ashei, Cupressus
      arizonica, C. sempervirens, Parietaria judaica, Olea europaea, and Lolium perenne
      pollen extracts were able to inhibit IgE binding to blotted rJun o 2 at different
      concentrations. CONCLUSION: rJun o 2 contains IgE-binding epitopes shared by
      taxonomically unrelated species, and therefore it can be regarded as a new
      panallergen. These findings could contribute to an explanation for the phenomenon
      of multiple positive test results in polysensitized patients and the potential
      symptom-eliciting role of allergenic sources previously not encountered.

PMID- 9648705
TI  - Diesel exhaust particles stimulate human airway epithelial cells to produce
      cytokines relevant to airway inflammation in vitro.
AB  - BACKGROUND: Epidemiologic and experimental studies suggest that air pollution
      such as diesel exhaust particles (DEPs), one of the important air pollutants, may
      play a role in the increasing prevalence of allergic airway diseases. OBJECTIVE:
      We studied the effect of suspended particulate matter (SPM) and its main
      component, DEPs, on the production of IL-8 and granulocyte-macrophage colony
      stimulating factor (GM-CSF) by human airway epithelial cells in vitro. METHODS:
      SPM obtained from high-volume air samplers and DEPs were added to cultured human
      nasal polyp-derived upper airway, normal bronchial, and transformed bronchial
      epithelial cells. Production of GM-CSF and IL-8 by airway epithelial cells was
      evaluated. RESULTS: Nontoxic doses of DEPs showed a significant stimulatory
      effect on IL-8 and GM-CSF production by these three kinds of epithelial cells in
      a dose- and time-dependent fashion. SPM had a stimulatory effect on GM-CSF, but
      not IL-8, production. These effects were abrogated by treatment with a protein
      synthesis inhibitor, cycloheximide, suggesting that the process required a de
      novo protein synthesis. On the double-chamber plates, airway epithelial cells
      responded to DEPs only when they were stimulated from the apical sides, which can
      be a model for in vivo environments. Neither charcoal nor graphite showed such
      stimulatory effects, indicating that the activity of DEPs did not derive from
      their particulate nature. Benzo(a)pyrene, one of the main aromatic hydrocarbons
      contained in DEPs, showed a stimulatory effect on the release of the cytokines,
      and this organic substance might have a causative effect on of the potency of
      DEPs. CONCLUSION: We conclude that SPM and DEPs, its main component, might be
      important air pollutants in the activation of airway epithelial cells for the
      release of cytokines relevant to allergic airway inflammation.

PMID- 9648706
TI  - Identification of IL-16 as the lymphocyte chemotactic activity in the
      bronchoalveolar lavage fluid of histamine-challenged asthmatic patients.
AB  - OBJECTIVE: We have previously demonstrated that the earliest lymphocyte
      chemotactic factors present in bronchoalveolar lavage fluid (BALF) of subjects
      with atopic asthma after subsegmental antigen challenge are IL-16 and MIP-1alpha,
      of which IL-16 appears to contribute a majority of the chemotactic activity.
      Because IL-16 is released in vitro after histamine stimulation of CD8+ T cells
      and epithelial cells, we evaluated the potential role of histamine in the release
      of IL-16 into the airways of allergic asthmatics in vivo. METHODS: Eight allergic
      asthmatic subjects, six normal subjects, and six atopic nonasthmatic subjects
      were challenged with saline in the lingula and with serial concentrations of
      histamine (1 x 10(-7) to 5 x 10(-5) mol/L) in the right middle lobe followed by
      bronchoalveolar lavage (BAL) 15 minutes and 6 hours later. RESULTS: The BALF from
      saline- and histamine-challenged lobes of normal subjects and atopic nonasthmatic
      subjects contained no significant lymphocyte chemoattractant activity. In six of
      the eight atopic asthmatic subjects, the histamine-challenged but not saline
      challenged segment contained IL-16 chemotactic activity but no other identifiable
      lymphocyte chemoattractant activities at 6 hours. CONCLUSIONS: IL-16 appears in
      the airways after histamine challenge and therefore could contribute to the
      earliest infiltration of CD4+ T cells and eosinophils observed after antigen
      challenge due to histamine release from mast cells.

PMID- 9648707
TI  - Ultrastructural analysis of human skin biopsy specimens from patients receiving
      recombinant human stem cell factor: subcutaneous injection of rhSCF induces
      dermal mast cell degranulation and granulocyte recruitment at the injection site.
AB  - We performed an ultrastructural analysis of 10 skin biopsy specimens that had
      been obtained from three women who were undergoing daily subcutaneous dosing with
      recombinant methionyl-human stem cell factor (rhSCF) as part of a phase I
      clinical trial. The biopsy specimens were obtained at sites of subcutaneous
      administration of rhSCF, within approximately 1 to 2 hours of rhSCF injection,
      and, at the same time, at contralateral control sites that had not been directly
      injected with rhSCF. We previously reported that subcutaneous dosing with rhSCF
      in these subjects induced the local development of a wheal and flare response,
      which was associated with evidence of mast cell degranulation, as well as a
      systemic increase in numbers of cutaneous mast cells. The present electron
      microscopic analysis revealed that all biopsies of swollen, erythematous rhSCF
      injected sites exhibited anaphylactic degranulation of both mature and immature
      mast cells, an acute inflammatory response characterized by the migration of
      neutrophils, basophils (some of which exhibited evidence of piecemeal
      degranulation), and eosinophils through blood vessel walls into the perivascular
      and extravascular spaces, and edema and fibrin deposition within the
      interstitium. By contrast, the control biopsies contained no evidence of mast
      cell degranulation or acute inflammation. However, both control and rhSCF
      injected sites exhibited mast cells that were undergoing granule building and
      maturation. Thus at the doses tested in these subjects, subcutaneous injection of
      rhSCF induced anaphylactic-type degranulation of dermal mast cells at the
      injection site, with an acute inflammatory response that was associated with the
      recruitment of granulocytes. By contrast, mast cells at sites distant from those
      directly injected with rhSCF exhibited no evidence of enhanced secretion.

PMID- 9648708
TI  - Cloning and sequencing of a gene encoding a 2S albumin seed storage protein
      precursor from English walnut (Juglans regia), a major food allergen.
AB  - BACKGROUND: Walnuts rank third in per capita consumption of tree nuts in the
      United States and can be associated with systemic IgE-mediated reactions in some
      individuals. OBJECTIVE: The objectives of the study were to clone a gene encoding
      one of the major food allergens in the walnut kernel and to characterize the
      recombinant allergen. METHODS: A cDNA expression library in the lambda vector Uni
      ZAP, which was prepared from walnut somatic embryos, was screened by using a
      patient's sera that reacted with multiple protein bands on immunoblotting.
      RESULTS: A cDNA clone containing an insert of 663 bp was identified and named Jug
      r 1. DNA sequence analysis of this clone revealed that it encoded a protein 142
      amino acids in length. Comparison of the encoded protein sequences with protein
      databases revealed that this clone exhibits a 46.1% identity with the Brazil nut
      (Bertholletia excelsa) methionine-rich 2S albumin seed storage protein precursor,
      Ber e 1. Jug r 1 appears to be an important walnut food allergen; 12 of 16 sera
      from patients allergic to walnuts demonstrated IgE binding to the 2S albumin seed
      storage protein precursor fusion protein. An IgE-binding inhibition study
      suggests that the walnut 2S protein precursor undergoes posttranslational
      modification into a large and small subunit that is similar to castor seed,
      cottonseed, mustard seed, and Brazil nut 2S seed storage protein allergens.
      Interestingly, the gene encoding this allergenic protein in Brazil nuts has
      recently gained notoriety because of its experimental use as a transgene to
      enhance the nutritional quality of legumes. CONCLUSION: This is now the sixth
      definitive 2S albumin seed storage protein demonstrated to bind IgE, suggesting
      that this class of proteins is inherently allergenic.

PMID- 9648709
TI  - Continued expression of anti-soy protein antibodies in rats bred on a soy protein
      free diet for one generation: the importance of dietary control in oral
      sensitization research.
AB  - BACKGROUND: One of the major factors that may have negatively affected the
      results of many oral sensitization studies in animals has been unscheduled
      dietary preexposure of the test animals or their parental generations to the
      antigen under investigation. OBJECTIVE: The influence of dietary preexposure to
      soy protein on oral sensitization studies with soy protein in Brown Norway rats
      was investigated. METHODS: Brown Norway rats bred on a soy protein-containing
      diet for several generations (routine bred [RB] animals) were placed on a soy
      protein-free diet during and for at least 6 months before breeding (F0 group).
      Four generations of offspring were bred on a soy protein-free diet (F1, F2, F3,
      and F4 groups). RB and F4 animals were exposed to soy protein either ad libitum
      through drinking water or parenterally with an adjuvant. RESULTS: In the F0 and
      F1 animals soy protein-specific IgG antibodies were still detectable, whereas no
      soy protein-specific IgG was detectable in the other generations tested. In RB
      animals no significant increase in soy protein-specific IgG titers occurred after
      exposure to soy protein. Enteral exposure of the F4 animals to soy protein
      resulted in sensitization to soy protein, with increased soy protein-specific IgG
      titers. CONCLUSIONS: These studies demonstrate that there is a continued
      expression of anti-soy protein antibodies in rats bred and raised on a soy
      protein-free diet for one generation. Not only must the test animals be bred and
      raised on a specified antigen-free diet, but their parental generations must also
      be bred in the same manner to avoid any problems in oral sensitization studies.

PMID- 9648710
TI  - A flow cytometric study about the immunopathology of vernal keratoconjunctivitis.
AB  - BACKGROUND: Vernal keratoconjunctivitis (VKC) is a bilateral seasonal
      conjunctival inflammation. Exact pathogenesis of the disease is unknown, but some
      evidences suggest TH lymphocyte-mediated immune reactions. OBJECTIVE: The aim of
      this study was to investigate the role of the T lymphocyte and its subsets in the
      pathogenesis of VKC. METHODS: We obtained tear samples from patients with VKC and
      normal volunteers during active (spring) and quiescent (winter) periods. The
      patients' records were also obtained for assessment of symptom scores. The
      percentages of CD4/29+, CD4/45RA+, CD4+, and CD8+ in tear samples were
      established by using flow cytometry, and the results of all three groups were
      compared with each other by using the Wilcoxon matched-pair signed-rank test and
      the Mann-Whitney U test. RESULTS: The percentages of CD4/29+ and CD4+ cells in
      tears of patients with VKC increased significantly in the active period and
      decreased to normal levels in the quiescent stage. In contrast, the percentages
      of CD4/45RA+ and CD8+ cells in tears of patients with VKC did not show any
      significant change between spring and winter. The patients' symptoms were
      significantly lower in the quiescent period (winter) compared with the active
      stage (spring). CONCLUSION: We propose that increased numbers of CD4+ and CD4/29+
      cells in tears may be exacerbating the disease during the spring season.

PMID- 9648711
TI  - Proinflammatory cytokine-induced and chemical mediator-induced IL-8 expression in
      human bronchial epithelial cells through p38 mitogen-activated protein kinase
      dependent pathway.
AB  - The p38 mitogen-activated protein (MAP) kinase is activated in various cells by
      proinflammatory cytokines and environmental stresses. However, little is known
      about the role of p38 MAP kinase in proinflammatory cytokine- and chemical
      mediator-induced cytokine expression in human bronchial epithelial cells (BECs).
      In this study we examined the role of p38 MAP kinase in IL-8 expression in BECs
      to clarify the signal transduction pathway regulating IL-8 expression in BECs
      stimulated with tumor necrosis factor-alpha (TNF-alpha), IL-1alpha, and platelet
      activating factor (PAF). We used TNF-alpha, IL-1alpha, and PAF as inducers for
      the analysis of the signal transduction pathway and determined IL-8 expression in
      BECs because TNF-alpha, IL-1alpha, and PAF are known to induce cytokine
      expression in BECs, and these proinflammatory cytokines and PAF are described to
      have a role in the production of allergic inflammation. The results showed that
      TNF-alpha, IL-1alpha, and PAF induced tyrosine phosphorylation of p38 MAP kinase
      in a dose- and time-dependent manner. The specific p38 MAP kinase inhibitor, SB
      203580, completely inhibited TNF-alpha-, IL-1alpha-, or PAF-induced IL-8 protein
      and mRNA expression in BECs. These results indicated that p38 MAP kinase plays an
      important role in TNF-alpha-, IL-1alpha-, or PAF-activated signaling pathway,
      which regulates IL-8 expression in BECs. In addition, these results provide new
      evidence on a strategy for treatment of airway inflammation with the specific p38
      MAP kinase inhibitor.

PMID- 9648712
TI  - Cloning of the American cockroach Cr-PII allergens: evidence for the existence of
      cross-reactive allergens between species.
AB  - BACKGROUND: Previously, we have identified the 28 and 32 kd proteins as
      additional important allergens from the American cockroach (Periplaneta
      americana) Cr-PII allergenic fraction. OBJECTIVE: The aim of this study was the
      cloning of P. americana Cr-PII allergens. METHODS: A lambdagt22A cDNA library
      constructed from P. americana mRNA was packaged into Escherichia coli Y1090 (r-),
      and clones recognized by murine anti-Cr-PII monoclonal antibodies and human IgE
      antibodies were isolated, sequenced, and subcloned into pET 21 and expressed in
      E. coli BL21(DE3). RESULTS: Six Cr-PII-positive clones recognized by human IgE
      antibodies were isolated. Two clones, C6 and C17, were sequenced, and we found
      encoding proteins of 228 and 274 amino acids with no cysteine or any potential N
      glycosylation site, with predicted masses of 25.8 and 31.14 kd, respectively.
      Both molecules contain internal repeated sequences with a 94% identity between
      them. C6 and C17 showed 59% and 77.3% skin reactivities, respectively, on 22
      cockroach-sensitive atopic patients. Both clones were found to have 28.9% to
      31.8% identities to ANG12 protein, a precursor of the African malaria mosquito
      (Anopheles gambiae) and 82.7% to 85.1% identity to a nucleotide sequence of the
      German cockroach (Blattella germanica) Bla g Bd90K allergen. The anti-C6 and anti
      C17 antibodies were able to recognize Cr-PII, recombinant proteins, five
      commercial American extracts, and two German cockroach extracts. Moreover, the
      binding of anti-C6 and anti-C17 antibodies to recombinant protein can be
      inhibited by B. germanica crude extract. Furthermore, Northern blot analyses have
      shown that B. germanica mRNAs could be detected by both cDNA probes. CONCLUSION:
      Our findings provide the first evidence of antigenic cross-reactivity between P.
      americana and B. germanica allergens on molecular levels. The results will be a
      great aid in facilitating the epitope mapping and improving diagnostic and
      therapeutic reagents for both cockroach species.

PMID- 9648713
TI  - T-lymphocyte responses to plicatic acid-human serum albumin conjugate in
      occupational asthma caused by western red cedar.
AB  - BACKGROUND: T cells are known to play a major role in the pathogenesis of atopic
      allergic asthma, but it is less clear whether they are involved in occupational
      asthma caused by low molecular weight chemicals such as plicatic acid.
      OBJECTIVES: We sought to determine whether peripheral blood T cells from patients
      with western red cedar asthma (WRCA) recognize plicatic acid (PA) conjugated to
      human serum albumin (HSA) as judged by proliferation or cytokine production and
      to analyze the response to PA inhalation with flow cytometry. RESULTS:
      Significant proliferative responses to PA-HSA were observed in eight of 33
      patients with WRCA, none of 10 exposed nonasthmatic cedar workers, and one of 18
      nonasthmatic control subjects. Two of 25 patients with WRCA also showed
      proliferative responses to unconjugated PA. All the WRCA responders were either
      currently exposed to cedar or had ceased exposure within the preceding 2 years.
      None of the four patients receiving oral steroids responded, but inhaled steroids
      did not seem to influence responsiveness. No correlations were found between the
      maximum stimulation response and any of the current FEV1 values, the current PC20
      methacholine values, or the magnitude of the late asthmatic response to PA.
      Peripheral blood T-cell subset proportions and their degree of activation were
      similar in patients with WRCA and exposed control subjects. There was no change
      in T-cell phenotypes or their activation markers after PA inhalation challenge.
      In vitro, PA-HSA stimulation did not affect subset ratios but led to release of
      small amounts of IL-5 and IFN-gamma, with no detectable increase in IL-4.
      CONCLUSIONS: PA-HSA-specific T lymphocytes seem to be present in small numbers in
      the peripheral blood of patients with WRCA and may respond to antigenic exposure
      by producing IFN-gamma and IL-5. However, the proportion of responding cells
      would appear to be lower than in comparable studies of atopic asthma.

PMID- 9648714
TI  - Slow subcutaneous human intravenous immunoglobulin in the treatment of antibody
      immunodeficiency: use of an old method with a new product.

PMID- 9648715
TI  - Food allergy to Boletus edulis.

PMID- 9648716
TI  - Rickets associated with gastrointestinal disease in a patient with chronic
      granulomatous disease.

PMID- 9648717
TI  - Food-dependent exercise-induced anaphylaxis to corn.

PMID- 9648718
TI  - Successful rush immunotherapy for anaphylaxis to imported fire ants.

PMID- 9648719
TI  - Mechanisms of transcriptional regulation of gene expression in smooth muscle
      cells.

PMID- 9648720
TI  - Gene transfer into normal and atherosclerotic human blood vessels.
AB  - Gene transfer to blood vessels is a promising new approach to the treatment of
      the vascular diseases, but the feasibility of gene transfer to adult human
      vessels has not been explored. We introduced an adenovirus vector encoding a
      marker gene human placental alkaline phosphatase into normal and atherosclerotic
      human vessels in organ culture. In the normal vessels, recombinant gene was
      expressed preferentially in the endothelial cells (approximately 100%), intimal
      smooth muscle cells (1.3+/-0.4%, 1.4+/-1.0%, and 3.8+/-0.8% in the internal
      mammary arteries, saphenous veins, and normal coronary arteries, respectively),
      and various adventitial cells. Advanced, complicated atherosclerotic plaques
      demonstrated a similar efficiency of recombinant gene expression (3.1+/-0.5% and
      3.8+/-0.3% of nonendothelial intimal cells in the coronary artery and carotid
      artery plaques, respectively). Of these intimal cells, macrophages and smooth
      muscle cells expressed a transgene, identifying them as targets for gene
      transfer. Areas of plaque rupture and thrombus are sites of predilection for
      expression of recombinant genes. Collagenase and elastase treatment increased the
      percentage of transgenic alkaline phosphatase-positive cells 7 times (P<0.001),
      suggesting that the pattern of gene expression was affected by the amount of
      surrounding extracellular matrix. These studies demonstrate the feasibility of
      gene transfer to human blood vessels. However, these studies also highlight
      important barriers to adenoviral gene delivery to the actual normal and
      atherosclerotic human vessels of clinical interest.

PMID- 9648721
TI  - Acute host-mediated endothelial injury after adenoviral gene transfer in normal
      rabbit arteries: impact on transgene expression and endothelial function.
AB  - Acute injury after adenoviral vascular gene transfer remains incompletely
      characterized. Here, we describe the early response (< or =days) in 52 New
      Zealand White rabbits undergoing gene transfer (beta-galactosidase or empty
      vector) or sham procedures to both carotid arteries. After gene transfer,
      arteries were either left in vivo for 1 hour to 3 days (in vivo arteries) or were
      excised immediately after gene transfer and cultured (ex vivo arteries). Within 1
      hour, in vivo arteries receiving infectious titers of > or = 4X10(9) plaque
      forming units (pfu)/mL showed endothelial activation, with an acute inflammatory
      infiltrate developing by 6 hours. Ex vivo arteries showed endothelial activation
      but no inflammatory infiltrate. There were also significant differences in
      transgene expression between in vivo and ex vivo arteries. Ex vivo arteries
      showed titer-dependent increases in beta-galactosidase expression through
      2X10(10) pfu/mL, whereas in in vivo arteries, titers above 4X10(9) pfu/mL merely
      increased acute inflammatory response, without increasing transgene expression.
      In vivo arteries showed significant time- and titer-dependent impairment in
      endothelium-dependent relaxation, with no effect on contraction or nitroprusside
      induced relaxation. Interestingly, however, if rabbits were made neutropenic with
      vinblastine, their arteries maintained full endothelium-dependent relaxation,
      even after very high titer vascular infection (up to 1X10(11) pfu/mL). These
      findings show that recombinant adenovirus triggers an early inflammatory
      response, and it is the inflammatory response that in turn causes functional
      endothelial injury. This occurs at much lower titers than previously appreciated
      (though the precise threshold will undoubtedly vary between laboratories).
      However, titers below the inflammatory threshold produce excellent transgene
      expression without inflammation or vascular injury.

PMID- 9648722
TI  - Role of nitric oxide in the control of renal oxygen consumption and the
      regulation of chemical work in the kidney.
AB  - Inhibition of NO synthesis has recently been shown to increase oxygen extraction
      in vivo, and NO has been proposed to play a significant role in the regulation of
      oxygen consumption by both skeletal and cardiac muscle in vivo and in vitro. It
      was our aim to determine whether NO also has such a role in the kidney, a tissue
      with a relatively low basal oxygen extraction. In chronically instrumented
      conscious dogs, administration of an inhibitor of NO synthase, nitro-L-arginine
      (NLA, 30 mg/kg i.v.), caused a maintained increase in mean arterial pressure and
      renal vascular resistance and a decrease in heart rate (all P<0.05). At 60
      minutes, urine flow rate and glomerular flow rate decreased by 44+/-12% and 45+/
      7%, respectively; moreover, the amount of sodium reabsorbed fell from 16+/-1.7 to
      8.5+/-1.1 mmol/min (all P<0.05). At this time, oxygen uptake and extraction
      increased markedly by 115+/-37% and 102+/-34%, respectively (P<0.05). Oxygen
      consumption also significantly increased from 4.5+/-0.6 to 7.1+/-0.9 mL O2/min.
      Most important, the ratio of oxygen consumption to sodium reabsorbed increased
      dramatically from 0.33+/-0.07 to 0.75+/-0.11 mL O2/mmol Na+ (P<0.05), suggesting
      a reduction in renal efficiency for transporting sodium. In vitro, both a NO
      donating agent and the NO synthase-stimulating agonist bradykinin significantly
      decreased both cortical and medullary renal oxygen consumption. In conclusion, NO
      plays a role in maintaining a balance between oxygen consumption and sodium
      reabsorption, the major ATP-consuming process in the kidney, in conscious dogs,
      and NO can inhibit mitochondrial oxygen consumption in canine renal slices in
      vitro.

PMID- 9648723
TI  - Angiotensin II stimulates p21-activated kinase in vascular smooth muscle cells:
      role in activation of JNK.
AB  - Angiotensin II (Ang II) has been previously shown to stimulate the extracellular
      signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) mitogen
      activated protein (MAP) kinase family members. Little is known regarding the
      upstream signaling molecules involved in Ang II-mediated JNK activation. Ang II
      has been shown to activate the Janus kinase/signal transducer(s) and activator(s)
      of transcription (JAK/STAT) pathway, suggesting similarities to cytokine
      signaling. In response to cytokines such as interleukin-1 and tumor necrosis
      factor-alpha, the p21-activated kinase (PAK) has been identified as an upstream
      component in JNK activation. Therefore, we hypothesized that PAK may be involved
      in JNK activation by Ang II in vascular smooth muscle cells (VSMCs). AlphaPAK
      activity was measured by myelin basic protein phosphorylation in rat aortic
      VSMCs. In response to Ang II, alphaPAK was rapidly stimulated within 1 minute,
      with a peak (5-fold increase) at 30 minutes. AlphaPAK stimulation preceded
      activation of JNK in VSMCs. Ang II-mediated activation of both alphaPAK and JNK
      was Ca2+ dependent and inhibited by downregulation of phorbol ester-sensitive
      protein kinase C isoforms (by pretreatment with phorbol 12,13-dibutyrate) but not
      by pretreatment with GF109203X. Activation of both PAK and JNK was partially
      inhibited by tyrosine kinase inhibitors but not by specific Src inhibitors,
      suggesting regulation by a tyrosine kinase other than c-Src. Finally,
      introduction of dominant negative PAK markedly reduced the JNK activation by Ang
      II in both Chinese hamster ovary and COS cells stably expressing the Ang II type
      1 receptor (AT1R). Our data provide evidence for alphaPAK as an upstream mediator
      of JNK in Ang II signaling and extend the role of Ang II as a proinflammatory
      mediator for VSMCs.

PMID- 9648724
TI  - Phosphorylation of p130Cas by angiotensin II is dependent on c-Src, intracellular
      Ca2+, and protein kinase C.
AB  - p130Cas is a signaling molecule that was initially found to be tyrosine
      phosphorylated in v-Crk and v-Src transformed cells. We characterized the
      regulation of p130Cas tyrosine phosphorylation in vascular smooth muscle cells by
      angiotensin II (Ang II). This ligand induced a transient increase in p130Cas
      tyrosine phosphorylation, which was sensitive to the actin polymerization
      inhibitor cytochalasin D and to the intracellular Ca2+ chelator BAPTA-AM but not
      the Ca2+ channel blocker verapamil. The Ang II-induced tyrosine phosphorylation
      of p130Cas was also dependent on an active Src family tyrosine kinase, since it
      could be blocked by the Src kinase inhibitors geldanamycin and PP1. Ang II
      treatment resulted in the ability of p130Cas to bind at least 11 different
      phosphate-containing proteins. Analysis of these proteins revealed that protein
      kinase Calpha and the cell adhesion signaling molecule pp120 formed temporal
      associations with p130Cas in response to Ang II. c-Src was found to associate
      with p130Cas in a manner that was independent of Ang II treatment. Inhibition of
      protein kinase C by either calphostin C or phorbol 12-myristate 13-acetate
      downregulation inhibited the Ang II-induced tyrosine phosphorylation of p130Cas.
      These results are the first to demonstrate that the tyrosine phosphorylation of
      p130Cas by Ang II is transduced by the Src, intracellular Ca2+, protein kinase C
      signaling pathway.

PMID- 9648725
TI  - Overexpression of human superoxide dismutase inhibits oxidation of low-density
      lipoprotein by endothelial cells.
AB  - Oxidation of LDL in the subendothelial space has been proposed to play a key role
      in atherosclerosis. Endothelial cells produce superoxide anions (O2.-) and
      oxidize LDL in vitro; however, the role of O2.- in endothelial cell-induced LDL
      oxidation is unclear. Incubation of human LDL (200 microg/mL) with bovine aortic
      endothelial cells (BAECs) for 18 hours resulted in a 4-fold increase in LDL
      oxidation compared with cell-free incubation (22.5+/-1.1 versus 6.3+/-0.2 [mean+/
      SEM] nmol malondialdehyde/mg LDL protein, respectively; P<0.05). Under similar
      conditions, incubation of LDL with porcine aortic endothelial cells resulted in a
      5-fold increase in LDL oxidation. Inclusion of exogenous copper/zinc superoxide
      dismutase (Cu/ZnSOD, 100 microg/mL) in the medium reduced BAEC-induced LDL
      oxidation by 79%. To determine whether the intracellular SOD content can have a
      similar protective effect, BAECs were infected with adenoviral vectors containing
      cDNA for human Cu/ZnSOD (AdCu/ZnSOD) or manganese SOD (AdMnSOD). Adenoviral
      infection increased the content and activity of either Cu/ZnSOD or MnSOD in the
      cells and reduced cellular O2.- release by two thirds. When cells infected with
      AdCu/ZnSOD or AdMnSOD were incubated with LDL, formation of malondialdehyde was
      decreased by 77% and 32%, respectively. Two other indices of LDL oxidation,
      formation of conjugated dienes and increased LDL electrophoretic mobility, were
      similarly reduced by SOD transduction. These data suggest that production of O2.-
      contributes to endothelial cell-induced oxidation of LDL in vitro. Furthermore,
      adenovirus-mediated transfer of cDNA for human SOD, particularly Cu/ZnSOD,
      effectively reduces oxidation of LDL by endothelial cells.

PMID- 9648726
TI  - Superoxide production in vascular smooth muscle contributes to oxidative stress
      and impaired relaxation in atherosclerosis.
AB  - The endothelium is a source of reactive oxygen species in short-term models of
      hypercholesterolemia and atherosclerosis. We examined a chronic model of
      atherosclerosis for increased vascular production of superoxide (O2-.) and
      determined whether endothelial overexpression of superoxide dismutase (SOD) would
      improve endothelium-dependent relaxation. Superoxide generation was 3 times
      higher in isolated aortas from Watanabe heritable hyperlipidemic (WHHL) rabbits
      (2 to 4 years old) compared with aortas from New Zealand White (NZ) rabbits (43+/
      10 versus 14+/-2 relative light units x min(-1) x mm(-2), n=9, P<0.05). After in
      vitro transduction with adenovirus containing the gene for CuZn-SOD (AdCMVCuZn
      SOD) or extracellular SOD (AdCMVEC-SOD), endothelial O2-. levels in WHHL aortas
      were significantly reduced. Gene transfer of SOD to WHHL aortas, however, failed
      to improve the impaired relaxation to acetylcholine or calcium ionophore. By use
      of the oxidative fluorescent dye hydroethidine, an in situ assay indicated
      markedly increased generation of O2-. throughout the wall of WHHL aorta,
      especially within layers of smooth muscle. This finding was confirmed by
      demonstrating increased O2-. levels in smooth muscle cells cultured from WHHL
      aorta. We conclude that elevated O2-. levels in atherosclerotic vessels are not
      confined to the endothelium but occur throughout the vascular wall, including
      smooth muscle cells. Reduction in endothelial O2-. levels is not sufficient to
      improve endothelium-dependent relaxation. Generation of reactive oxygen species
      within the media may contribute to vasomotor dysfunction in atherosclerosis.

PMID- 9648727
TI  - Atypical protease-activated receptor mediates endothelium-dependent relaxation of
      human coronary arteries.
AB  - Protease-activated receptors (PARs) are a family of G protein-coupled receptors
      activated by a tethered ligand sequence within the amino terminal that are
      revealed by site-specific proteolysis. The thrombin-sensitive PAR-1 and trypsin
      activated PAR-2 mediate endothelium-dependent vascular relaxation in a number of
      species. Because both thrombin and trypsin-like enzymes have been implicated in
      coronary artery disease, the purpose of this study was to investigate whether
      similar receptors are present in human coronary arteries. Thrombin (0.001 to 0.1
      U/mL) and trypsin (0.001 to 1 U/mL) caused concentration- and endothelium
      dependent relaxations of human coronary artery ring segments suspended in organ
      chambers for isometric tension recording and contracted with the thromboxane A2
      mimetic U46619. These relaxations were dependent on the catalytic activity of
      each enzyme and were inhibited by the NO synthase inhibitor NG-nitro-L-arginine
      (100 micromol/L) and the NO scavenger oxyhemoglobin (20 micromol/L). The
      synthetic PAR-1 tethered ligand sequence SFLLRN-NH2 (0.01 to 10 micromol/L) also
      caused endothelium-dependent relaxation of U46619-contracted human coronary
      arteries; however, the equivalent PAR-2 ligand SLIGKV-NH2 caused almost no
      relaxation. In addition, desensitization to either thrombin or trypsin resulted
      in cross-desensitization to the other enzyme but had only a minimal affect on the
      response to SFLLRN-NH2. Therefore, we conclude that human coronary artery
      endothelial cells possess a PAR-1-like receptor that is potently activated by
      thrombin, trypsin, and SFLLRN-NH2 to cause NO-mediated vascular relaxation. Once
      cleaved, this receptor is recycled in a truncated form, able to respond to
      exogenous application of only its tethered ligand sequence, suggesting the
      presence of another endogenous activator possibly acting independently of
      receptor cleavage.

PMID- 9648728
TI  - Autonomic control of vasomotion in the porcine coronary circulation during
      treadmill exercise: evidence for feed-forward beta-adrenergic control.
AB  - To date, no studies have investigated coronary vasomotor control of myocardial O2
      delivery (MDO2) and its modulation by the autonomic nervous system in the porcine
      heart during treadmill exercise. We studied 8 chronically instrumented swine
      under resting conditions and during graded treadmill exercise. Exercise up to 85%
      to 90% of maximum heart rate produced an increase in myocardial O2 consumption
      (MVO2) from 163+/-16 micromol/min (mean+/-SE) at rest to 423+/-75 micromol/min
      (P< or =0.05), which was paralleled by an increase in MDO2, so that myocardial O2
      extraction (79+/-1% at rest) and coronary venous O2 tension (cvPO2, 23.7+/-1.0 mm
      Hg at rest) were maintained. Beta-adrenoceptor blockade blunted the exercise
      induced increase of MDO2 out of proportion compared with the attenuation of the
      exercise-induced increase in MVO2, so that O2 extraction rose from 78+/-1% at
      rest to 83+/-1% during exercise and cvPO2 fell from 23.5+/-0.9 to 19.6+/-1.1 mm
      Hg (both P< or =0.05). In contrast, alpha-adrenoceptor blockade, either in the
      absence or presence of beta-adrenoceptor blockade, had no effect on myocardial O2
      extraction or cvPO2 at rest or during exercise. Muscarinic receptor blockade
      resulted in a decreased O2 extraction and an increase in cvPO2 at rest, an effect
      that waned during exercise. The vasodilation produced by muscarinic receptor
      blockade was likely due to an increased beta-adrenoceptor activity, since
      combined muscarinic and beta-adrenoceptor blockade produced similar changes in O2
      extraction and cvPO2, as did beta-adrenoceptor blockade alone. In conclusion, in
      swine myocardium, MVO2 and MDO2 are matched during exercise, which is the result
      of feed-forward beta-adrenergic vasodilation in conjunction with minimal a
      adrenergic vasoconstriction. Beta-adrenergic vasodilation is due to an increase
      in sympathetic activity but may also be supported by withdrawal of muscarinic
      receptor-mediated inhibition of beta-adrenergic coronary vasodilation. The
      observation that cvPO2 levels are maintained even during heavy exercise suggests
      that a decrease in cvPO2 is not essential for coronary vasodilation during
      exercise.

PMID- 9648729
TI  - Nitric oxide inhibits alpha2-adrenoceptor-mediated endothelium-dependent
      vasodilation.
AB  - This study was designed to investigate the interaction between the NO/L-arginine
      pathway and the alpha2-adrenoceptor-mediated endothelium-dependent
      vasorelaxation. Reactivity of isolated resistance mesenteric arterial segments
      from mice lacking the gene for constitutive endothelial NO synthase (eNOS- mice,
      n=14) and from their wild-type controls (WT mice, n=46) was studied in isometric
      conditions in the presence of indomethacin (blocker of cyclooxygenase).
      Oxymetazoline (OXY, 0.01 to 30 micromol/L; a selective alpha2-adrenoceptor
      agonist) induced an endothelium-dependent relaxation of eNOS- but not WT arteries
      preconstricted either with phenylephrine or serotonin. In the presence of Nomega
      nitro-L-arginine (l-NNA, 100 micromol/L), an inhibitor of NOS, OXY induced an
      endothelium-dependent relaxation of WT mesenteric arteries. l-NNA had no effect
      on the relaxation caused by OXY in eNOS- arterial rings. Therefore, the
      relaxation caused by OXY was independent of NO formation. To demonstrate the
      inhibitory role of NO on the alpha2-adrenoceptor-mediated relaxation,
      subthreshold (0.1 nmol/L) to threshold (1 nmol/L) concentrations of sodium
      nitroprusside (donor of NO) were added to l-NNA-treated arteries before OXY
      challenges: in these conditions, the alpha2-adrenoceptor-mediated relaxation of
      eNOS- and WT arteries was inhibited. OXY-induced relaxation was restored on
      readdition of methylene blue (1 micromol/L, inhibitor of guanylate cyclase),
      suggesting that cGMP may be the mechanism of inhibition of the alpha2-adrenergic
      pathway in the presence of NO. Finally, OXY-mediated relaxation was blocked by
      tetraethylammonium (1 mmol/L) but not glibenclamide (1 micromol/L), suggesting
      the involvement of an endothelium-derived hyperpolarizing factor that activates
      Ca2+-activated K+ channels. In conclusion, alpha2-adrenoceptor activation caused
      relaxation of isolated murine mesenteric arteries that was functionally blocked
      by NO through a mechanism that may involve activation of the soluble guanylate
      cyclase and cGMP formation. The endothelium-dependent alpha2-adrenoceptor
      mediated relaxation is likely to be due to an endothelium-derived hyperpolarizing
      factor, whose release and/or production is reduced by concurrent NO formation.

PMID- 9648730
TI  - Increase in functional Ca2+ channels in cerebral smooth muscle with renal
      hypertension.
AB  - The hypothesis that availability of functional Ca2+ channels in vascular smooth
      muscle is augmented in hypertension was tested in basilar artery cells from
      Wistar rats exhibiting stable systolic blood pressure (BPsys) for 2 to 11 weeks
      after partial renal artery ligation (Goldblatt 2-kidney 1-clip [2K1C] model).
      Cells were freshly isolated and patch-clamped using a nystatin-perforated patch
      method. BPsys ranged from 110 to 280 mm Hg and correlated with normalized kidney
      mass. Macroscopic current-voltage curves were fit to a Boltzmann function to
      obtain maximum conductance (gmax), steepness and midpoint potential for the
      voltage dependence of activation (k and E1/2, respectively), and extrapolated
      reversal potential for the chord conductance (Erev). Linear regression of
      normalized conductance (ng(max)=g(max)/cell capacitance) versus BPsys for 103
      cells indicated a strong relationship, with a slope of 0.0019 nS x pF(-1) x mm
      Hg(-1) (P<0.0001). Similar analysis of data from 35 other cells exposed to 500
      nmol/L Bay K 8644 gave a slope of 0.0041 nS x pF(-1) x mm Hg(-1) (P=0.001).
      Voltage-dependent parameters, k, E1/2, and Erev, were not significantly related
      to BPsys. Single-channel measurements in cell-attached patches revealed that the
      number of channels in 32 patches was significantly related to BPsys (P=0.0024)
      but that slope conductance, open dwell times at 0 mV, and distribution between 2
      open states were not. Finally, in a subgroup of 61 cells from animals made
      hypertensive (180 mm Hg<BPsys<200 mm Hg) for approximately 1/2 to 6 weeks, we
      found that elevation of ngmax depended on duration of hypertension (P=0.003),
      with no elevation at approximately 1/2 week. We conclude that in the 2K1C model,
      availability of functional Ca2+ channels increases with BPsys with no change in
      channel properties and that measurable BPsys elevation occurs before the increase
      in functional channels.

PMID- 9648731
TI  - Angiotensin II type 1 receptor-induced extracellular signal-regulated protein
      kinase activation is mediated by Ca2+/calmodulin-dependent transactivation of
      epidermal growth factor receptor.
AB  - The signaling cascade elicited by angiotensin II (Ang II) resembles that
      characteristic of growth factor stimulation, and recent evidence suggests that G
      protein-coupled receptors transactivate growth factor receptors to transmit
      mitogenic effects. In the present study, we report the involvement of epidermal
      growth factor receptor (EGF-R) in Ang II-induced extracellular signal-regulated
      kinase (ERK) activation, c-fos gene expression, and DNA synthesis in cardiac
      fibroblasts. Ang II induced a rapid tyrosine phosphorylation of EGF-R in
      association with phosphorylation of Shc protein and ERK activation. Specific
      inhibition of EGF-R function by either a dominant-negative EGF-R mutant or
      selective tyrphostin AG1478 completely abolished Ang II-induced ERK activation.
      Induction of c-fos gene expression and DNA synthesis were also abolished by the
      inhibition of EGF-R function. Calmodulin or tyrosine kinase inhibitors, but not
      protein kinase C (PKC) inhibitors or downregulation of PKC, completely abolished
      transactivation of EGF-R by Ang II or the Ca2+ ionophore A23187. Epidermal growth
      factor (EGF) activity in concentrated supernatant from Ang II-treated cells was
      not detected, and saturation of culture media with anti-EGF antibody did not
      affect the Ang II-induced transactivation of EGF-R. Conditioned media in which
      cells were incubated with Ang II could not induce phosphorylation of EGF-R on
      recipient cells. Platelet-derived growth factor-beta receptor was not
      phosphorylated on Ang II stimulation, and Ang II-induced c-jun gene expression
      was not affected by tyrphostin AG1478. Our results demonstrated that in cardiac
      fibroblasts Ang II-induced ERK activation and its mitogenic signals are
      dominantly mediated by EGF-R transactivated in a Ca2+/calmodulin-dependent manner
      and suggested that the effects of Ang II on cardiac fibroblasts should be
      interpreted in association with the signaling pathways regulating cellular
      proliferation and/or differentiation by growth factors.

PMID- 9648732
TI  - Lessons from human arteries: how to design a gene therapy strategy for treatment
      of cardiovascular disease.

PMID- 9648733
TI  - Versatility of the angiotensin II type 1 receptor.

PMID- 9648734
TI  - Identification of elicitor-induced cytochrome P450s of soybean (Glycine max L.)
      using differential display of mRNA.
AB  - Elicitor-inducible glyceollin biosynthesis in soybean depends on five presumably
      transcriptionally regulated cytochrome P450-dependent enzymes (P450s). In order
      to isolate corresponding cDNA clones, we devised a novel polymerase chain
      reaction (PCR)-based approach targeting P450s that are transcriptionally
      activated under glyceollin-inducing conditions. The differential display of mRNA
      (DD-RT-PCR) technique was performed with upstream primers based on the conserved
      heme-binding region of P450s, and ten different 3'-terminal partial P450
      sequences were isolated. They were subsequently used to isolate nine different
      full-length cDNA clones from a cDNA library. As shown by Northern blot analysis,
      eight of the clones represented P450s, which were activated under glyceollin
      inducing conditions similar to two enzymes of the glyceollin biosynthesis
      pathway, CHS and IFR. Therefore, these eight clones are candidate cDNAs for the
      glyceollin-related P450s. Functional expression in yeast identified one cDNA
      clone coding for cinnamate 4-hydroxylase. Thus, at least one of the isolated
      clones definitively encodes a P450 of the glyceollin pathway. Consequently, this
      approach offers a straightforward alternative to classical P450 isolation
      strategies via protein purification and should prove especially useful for
      isolating P450s that are expressed at a low level.

PMID- 9648735
TI  - DNA analysis of temperate bacteriophage Aa(phi)23 isolated from actinobacillus
      actinomycetemcomitans.
AB  - The DNA of the temperate bacteriophage Aaphi23 isolated from the oral bacterium
      Actinobacillus actinomycetemcomitans was examined structurally both in the phage
      head and in the prophage. The DNA in phage particles comprises 44 kb linear
      molecules with a terminal redundancy of 1.6 kb, which represent circular
      permutations. Thus, DNA is packaged into phage heads by the headful mechanism.
      The Aaphi23 prophage is integrated into the host chromosome.

PMID- 9648736
TI  - Effect of signal peptide changes on the extracellular processing of streptokinase
      from Escherichia coli: requirement for secondary structure at the cleavage
      junction.
AB  - Streptokinase (SK), an extracellular protein from Streptococcus equisimilis, is
      secreted post-translationally by Escherichia coli using both its native and E.
      coli-derived transport signals. In this communication we report that cleavage
      specificity of signal peptidase I, and thus efficiency of secretion, varies in E.
      coli when SK export is directed by different transport signals. The native (+1) N
      terminus of mature SK was retained when it was transported under the control of
      its own, PelB or LamB signal peptide. However, when translocation of SK was
      controlled by the OmpA or MalE signal peptide, Ala2 of mature SK was preferred as
      a cleavage site for the pre-SK processing. Our results indicate that
      compatibility of the leader peptide with the mature sequences of SK, which
      fulfills the requirement for a given secondary structure within the cleavage
      region, is essential for maintaining the correct processing of pre-SK. An OmpA-SK
      fusion, which results in the deletion of two N-terminal amino acid residues of
      mature SK, was further studied with respect to the recognition of alternative
      cleavage site in E. coli. The alanine at +2 in mature SK was changed to glycine
      or its relative position was changed to +3 by introducing a methionine residue at
      the +1 position. Both alterations resulted in the correct cleavage of pre-SK at
      the original OmpA fusion site. In contrast, introduction of an additional alanine
      at +4, creating three probable cleavage sites (Ala-x-Ala-x-Ala-x-Ala), resulted
      in the recognition of all three target sites for cleavage, with varying
      efficiency. The results indicate that the nature of the secondary structure
      generated at the cleavage junction of pre-SK, resulting from the fusion of
      different signal peptides, modulates the cleavage specificity of signal peptidase
      I during extracellular processing of SK. Based on these findings it is proposed
      that flexibility in the interaction of the active site of signal peptidase I with
      the cleavage sites of signal peptides may occur when it encounters two or more
      juxtaposed cleavage sites. Preference for one cleavage site over another, then,
      may depend on fulfillment of secondary structure requirements in the vicinity of
      the pre-protein cleavage junction.

PMID- 9648737
TI  - Involvement of the rolled/MAP kinase gene in Drosophila mitosis: interaction
      between genes for the MAP kinase cascade and abnormal spindle.
AB  - We have found that mutations that lead to loss of rolled/MAP kinase function
      result in a reduced mitotic index in the larval central nervous system,
      consistent with an interphase block to cell cycle progression, associated with a
      low frequency of cells showing chromosome over-condensation in mitosis and
      abnormal anaphase figures. In contrast to wild-type tissue, such rolled mutants
      do not show a significant increase in accumulation of mitotic cells when treated
      with colchicine. We have studied double mutant combinations between mutations
      affecting the activity of rolled/MAP kinase and several genes that are essential
      to the establishment of a bipolar spindle during progression through mitosis, and
      find no interactions with mutations in polo, mgr, or aurora. However, partial
      loss-of-function mutations in rolled enhance the abnormal spindle (asp)
      phenotype, whereas gain-of function mutations in rolled or in the gene encoding
      its activating kinase Dsor1, act as suppressors. We discuss these findings in
      relation to the proposed role of MAP kinase in mediating the spindle integrity
      checkpoint.

PMID- 9648738
TI  - The PAC protein affects the maturation of specific chloroplast mRNAs in
      Arabidopsis thaliana.
AB  - The pale cress (pac) mutation arrests chloroplast development at an early stage
      in Arabidopsis thaliana and leads to a white phenotype. Chlorophyll fluorescence
      measurements demonstrated that the photosynthetic apparatus was impaired. The
      mutation did not reduce transcription of nuclear genes with photosynthetic
      function. However, distinct chloroplast-encoded transcripts were affected. The
      mutation mainly changed the maturation pattern, but the abundance of specific
      transcripts was also reduced. The defects observed imply a specific role for PAC
      in chloroplast mRNA maturation. PAC is encoded by a nuclear gene and is
      transported into the chloroplast. Therefore PAC may be one of the nucleus-encoded
      factors that function in plastid mRNA maturation and accumulation.

PMID- 9648739
TI  - Degradation of hammerhead ribozymes by human ribonucleases.
AB  - Hammerhead ribozymes were used as substrates to examine endoribonucleolytic
      activities in cell extracts and cultured human cells. Primer-extension analyses
      showed that ribozymes directed against tumor necrosis factor-alpha mRNA and human
      immunodeficiency virus type 1 tat mRNA were cleaved at UA and CA dinucleotides by
      extracts. Preferred cleavage sites were similar to those observed following
      digestion with RNase A, and cleavage was blocked by RNasin, an inhibitor of
      pyrimidine-specific ribonucleases. Removal of UA and CA dinucleotides rendered
      ribozymes more stable when incubated in cell extracts that were not significantly
      contaminated by extracellular nucleases. Placement of UA dinucleotides adjacent
      to a ribozyme in mRNA led to excision of the ribozyme from long transcripts
      during incubation in extracts. UA dinucleotides also made mRNA more labile than a
      control RNA when expressed from an endogenous plasmid gene in the human myeloid
      cell line U937. Similarly, UA and CA dinucleotides caused ribozymes to have a
      shorter half-life when delivered to U937 cells by lipofectin-mediated
      transformation. Taken together, these data indicate that one or more members of
      the pyrimidine-specific ribonuclease family is involved in the intracellular
      degradation of RNA, and they explain the paucity of UA dinucleotides in
      eukaryotic mRNA. Judicious manipulation of preferred target sequences of
      pyrimidine-specific ribonucleases may be useful in designing effective hammerhead
      ribozymes.

PMID- 9648740
TI  - Cloning of an EF-P homologue from Bacteroides fragilis that increases B. fragilis
      glutamine synthetase activity in Escherichia coli.
AB  - Investigations of possible regulators of Bacteroides fragilis glutamine
      synthetase (GS) activity were done in Escherichia coli using a compatible dual
      plasmid system. The B. fragilis glnA gene, together with upstream and downstream
      flanking regions, was cloned onto the low copy number plasmid pACYC184 and
      expressed in the E. coli glnA ntrB ntrC deletion strain, YMC11. GS activity was
      monitored following co-transformation with a B. fragilis genomic library carried
      on the compatible plasmid pEcoR251. A gene was cloned that caused a twofold
      increase in B. fragilis GS activity but did not affect the activity of the E.
      coli GS enzyme or the B. fragilis sucrase (ScrL). Deletion of the B. fragilis
      glnA downstream region decreased basal levels of GS activity, but did not affect
      the ability of the cloned gene to increase the B. fragilis GS activity. Reporter
      gene analysis, using the B. fragilis glnA promoter region fused to the
      promoterless Clostridium acetobutylicum endoglucanase gene, showed no increase in
      reporter gene activity. This demonstrated that the increase in GS activity was
      not regulated at the transcriptional level, and that the cloned gene product was
      not affecting the copy number of the plasmid in trans. Sequence data indicated
      that the cloned gene had good amino acid identity to a range of elongation factor
      P (EF-P) proteins, the highest being to that of a Synechocystis sp (48%), and the
      least to Mycobacterium genitalium (27%). Amino acid identity to the E. coli EF-P
      was intermediate (37%). A possible role for EF-P in enhancing translation of the
      B. fragilis glnA mRNA is proposed.

PMID- 9648741
TI  - Three Nrt2 genes are differentially regulated in Chlamydomonas reinhardtii.
AB  - Two new nitrate assimilation-related genes, Nrt2;3 and Nar5, have been identified
      in Chlamydomonas reinhardtii. The Nrt2;3 gene is a new member of the Nrt2 family,
      encoding high-affinity nitrate (nitrite) transporters. Like that of the nitrate
      assimilation genes, expression of the Nrt2;3 gene is down-regulated by ammonium
      and positively controlled by Nit2, a regulatory locus specific for the pathway.
      The three Nrt2 genes of C. reinhardtii are differentially regulated by the
      nitrogen source. Expression of Nrt2;3 and of Nrt2;1, a nitrate/nitrite-bispecific
      transporter gene, was induced by nitrate and more efficiently by nitrite.
      Accumulation of mRNA of Nrt2;2, the nitrate-specific transporter gene, was only
      induced efficiently by nitrate. The Nar5 gene is located upstream of the Nrt2;3
      genomic region and expression of its mRNA is down-regulated by ammonium. The
      Nrt2;3 and Nar5 genes are overexpressed in a deletion mutant that lacks nitrate
      assimilation loci.

PMID- 9648742
TI  - Genetic localization of a bruchid resistance gene and its relationship to
      insecticidal cyclopeptide alkaloids, the vignatic acids, in mungbean (Vigna
      radiata L. Wilczek).
AB  - Bruchid resistance, controlled by a single dominant gene (Br) in a wild mungbean
      accession (TC1966), has been incorporated into cultivated mungbean (Vigna
      radiata). The resistance gene simultaneously confers inhibitory activity against
      the bean bug, Riptortus clavatus Thunberg (Hemiptera: Alydidae). The resultant
      isogenic line (BC20 generation) was characterized by the presence of a group of
      novel cyclopeptide alkaloids, called vignatic acids. A linkage map was
      constructed for Br and the vignatic acid gene (Va) using restriction fragment
      length polymorphism (RFLP) markers and a segregating BC20F2 population. By
      screening resistant and susceptible parental lines with 479 primers, eight
      randomly amplified polymorphic DNA (RAPD) markers linked to Br were identified
      and cloned for use as RFLP probes. All eight RAPD-based markers, one mungbean,
      and four common bean genomic clones were effectively integrated around Br within
      a 3.7-cM interval. Br was mapped to a 0.7-cM segment between a cluster consisting
      of six markers and a common bean RFLP marker, Bng110. The six markers are closest
      to the bruchid resistance gene, approximately 0.2 cM away. The vignatic acid
      gene, Va, cosegregated with bruchid resistance. However, one individual was
      identified in the BC20F2 population that retained vignatic acids in spite of its
      bruchid susceptibility. Consequently, Va was mapped to a single locus at the same
      position as the cluster of markers and 0.2 cM away from Br. These results suggest
      that the vignatic acids are not the principal factors responsible for bruchid
      resistance in V. radiata but will facilitate the use of map-based cloning
      strategies to isolate the Br gene.

PMID- 9648743
TI  - The UP element of the promoter for the flagellin gene, hag, stimulates
      transcription from both SigD- and SigA-dependent promoters in Bacillus subtilis.
AB  - DNA sequences upstream (UP element) of the core promoter (-10, -35 region) of the
      Bacillus subtilis flagellin gene hag stimulate transcription in vivo and in
      vitro. We constructed a number of hybrids, placing the UP element of hagp
      upstream of the core of one SigD-dependent (fliDp) and two SigA-dependent (tmsp,
      vegp) B. subtilis promoters. The hybrid promoters were fused to a lacZ reporter
      gene and their activity tested in vivo. The presence of the UP module enhanced
      transcription at both types of promoters. We conclude that the hagp UP sequence
      can act as a promoter module independently of the core sequence.

PMID- 9648744
TI  - Relocation of urf a from the mitochondrion to the nucleus cures the mitochondrial
      mutator phenotype in the fission yeast Schizosaccharomyces pombe.
AB  - In previous papers we have reported the characterisation of mitochondrial mutator
      mutants of Schizosaccharomzyces pombe. In contrast to nuclear mutator mutants
      known from other eucaryotes, this mutator phenotype correlates with mutations in
      an unassigned open reading frame (urf a) in the mitochondrial genome. Since an
      efficient biolistic transformation system for fission yeast mitochondria is not
      yet available, we relocated the mitochondrial urf a gene to the nucleus. As host
      strain for the ectopic expression, we used the nonsense mutant ana(r)-6, which
      carries a premature stop codon in the urf a gene. The phenotype of this mutant is
      characterised by continuous segregation of progeny giving rise to fully
      respiration competent colonies, colonies that show moderate growth on glycerol
      and a fraction of colonies that are unable to grow on glycerol. The phenotype of
      this mutant provides an excellent tool with which to study the effects on the
      mutator phenotype of ectopic expression of the urf a gene. Since a UGA codon
      encoding tryptophan is present in the original mitochondrial gene, we constructed
      two types of expression cassettes containing either the mitochondrial version of
      the urf a gene (mt-urf a) or a standard genetic code version (nc-urf a; UGA
      replaced by UGG) fused to the N-terminal import leader sequence of the cox4 gene
      of Saccharomyces cerevisiae. We show that the expression of the mt-urf a gene in
      its new location is able to cure, at least in part, the phenotype of mutant
      ana(r)-6, whereas the expression of the nc-urf a gene completely restores the
      wild-type (non-mutator) phenotype. The significant similarity of the urf a gene
      to the mitochondrial var1 gene of S. cerevisiae and homologous genes in other
      yeasts suggests that the urf a gene product might be a ribosomal protein with a
      dual function in protein synthesis and maintenance of mitochondrial DNA
      integrity.

PMID- 9648745
TI  - Polymorphism of the S-locus glycoprotein gene (SLG) and the S-locus related gene
      (SLR1) in Raphanus sativus L. and self-incompatible ornamental plants in the
      Brassicaceae.
AB  - The S-locus glycoprotein gene, SLG, which participates in the pollen-stigma
      interaction of self-incompatibility, and its unlinked homologue, SLR1, were
      analyzed in Raphanus sativus and three self-incompatible ornamental plants in the
      Brassicaceae. Among twenty-nine inbred lines of R. sativus, eighteen S haplotypes
      were identified on the basis of DNA polymorphisms detected by genomic Southern
      analysis using Brassica SLG probes. DNA fragments of SLG alleles specifically
      amplified from eight S haplotypes by PCR with class I SLG-specific primers showed
      different profiles following polyacrylamide gel electrophoresis, after digestion
      with a restriction endonuclease. The nucleotide sequences of the DNA fragments of
      these eight R. sativus SLG alleles were determined. Degrees of similarity of the
      nucleotide sequences to a Brassica SLG (S6SLG) ranged from 85.6% to 91.9%. Amino
      acid sequences deduced from these had the twelve conserved cysteine residues and
      the three hypervariable regions characteristic of Brassica SLGs. Phylogenetic
      analysis of the SLG sequences from Raphanus and Brassica revealed that the
      Raphanus SLGs did not form an independent cluster, but were dispersed in the
      tree, clustering together with Brassica SLGs. These results suggest that
      diversification of the SLG alleles of Raphanus and Brassica occurred before
      differentiation of these genera. Although SLR1 sequences from Orychophragmus
      violaceus were shown to be relatively closely related to Brassica and Raphanus
      SLR1 sequences, DNA fragments that are highly homologous to the Brassica SLG were
      not detected in this species. Two other ornamental plants in the Brassicaceae,
      which are related more distantly to Brassica than Orychophragmus, also lacked
      sequences highly homologous to Brassica SLG genes. The evolution of self
      incompatibility in the Brassicaceae is discussed.

PMID- 9648746
TI  - The uvp1 gene on the R46 plasmid encodes a resolvase that catalyzes site-specific
      resolution involving the 5'-conserved segment of the adjacent integron In1.
AB  - The product of the uvp1 gene of the R46 plasmid, a member of the DNA invertase
      resolvase family, was studied to characterize its recombination activity on the
      R46 plasmid. The purified Uvp1 protein specifically binds to a 256-bp DNA
      fragment located immediately upstream of the uvp1 gene itself, and overlapping
      the 5'-conserved segment (5'-CS) of the R46 integron In1. We identified on this
      fragment a putative resolution (res) site. Using an in vitro assay, we
      demonstrated the ability of the protein to resolve a synthetic cointegrate
      containing a direct repeat of the res site. In vivo, we obtained cointegrate
      resolution in Uvp1-expressing recA- cells. Sites I and II, subsites of the
      putative res site, lie within the outer boundary of the integron 5'-CS which is
      common to all the known integrons. Furthermore, a 69-bp DNA element (containing
      site I) is required for cointegrate resolution. We propose that this
      recombination mechanism protects R46 plasmid against unequal distribution
      following fusion with either identical or different integron-bearing plasmids.
      Moreover, Uvp1 might have a role in generating gene cassette diversity between
      the two conserved segments of the integron.

PMID- 9648747
TI  - Jasmonic acid-dependent and -independent wound signal transduction pathways are
      differentially regulated by Ca2+/calmodulin in Arabidopsis thaliana.
AB  - We have used wound- and jasmonic acid (JA)-responsive genes as molecular markers
      to elucidate the pathway(s) of wound signal transduction in Arabidopsis thaliana.
      The JA-responsive (JR) genes JR1, JR2, and JR3 are strongly induced by wounding
      and by JA, while the wound-responsive (WR) genes WR3 and acyl CoA oxidase (ACO)
      are induced by wounding only. Accumulation of JR transcripts upon wounding was
      blocked by indomethacin. However, indomethacin did not affect either induction of
      these genes by JA or wound-induced expression of WR genes, suggesting that JA
      synthesis is only needed for wound-dependent induction of JR genes, and also that
      separate JA-dependent and -independent wound signal transduction pathways exist
      in Arabidopsis. The two pathways are differentially regulated by Ca2+ and
      calmodulin. Mobilization of intracellular Ca2+ pools blocked induction of JR
      genes by both wounding and JA, but not the induction of WR genes by wounding, but
      this effect could not be reproduced by increasing intracellular Ca2+ levels using
      ionophores. In addition, calmodulin antagonists blocked the expression of JR
      genes and up-regulated WR gene expression. Ca2+ and calmodulin seem to act
      downstream of both JA and the COI1 gene in the JA-dependent pathway, and
      downstream of reversible phosphorylation events that differentially regulate JA
      dependent and JA-independent wound signal transduction pathways.

PMID- 9648748
TI  - Promoter regions of four Balbiani ring genes in Chironomus tentans exhibit a
      common salivary gland-specific chromatin organisation, which is independent of
      the rate of transcriptional initiation.
AB  - The Balbiani ring (BR) gene family consists of four closely related genes which
      show some differences in transcriptional regulation. Here we analyse the
      chromatin structure of the promoter regions of the four BR genes. In cells in
      which the genes are inactive, digestion of chromatin with micrococcal nuclease
      suggests for the BR1 gene that precisely positioned nucleosomes are present from
      position +200 to -600. In salivary gland cells, a distinctly different
      organisation of the promoter chromatin leads to the appearance of two sites that
      are hypersensitive to both DNase I and micrococcal nuclease, located at the
      approximate positions -50 and -240. Nuclease digestion experiments suggest the
      presence of a nucleosome in the region between the two hypersensitive sites, and
      nucleosome disruption at the transcription initiation site. The positions of
      these hypersensitive sites in all BR genes is unaffected by extensive modulation
      of the rate of transcriptional initiation, although some alterations in the
      intensity of the hypersensitive sites were observed. We also show that total
      nucleosome displacement from the transcribing template is seen only when the RNA
      polymerase density exceeds one polymerase molecule per 100 bp.

PMID- 9648749
TI  - Genes encoding thymidylate synthases A and B in the genus Bacillus are members of
      two distinct families.
AB  - Bacillus subtilis strain 168 is known to possess two genes that encode
      thymidylate synthases, thyA and thyB. We have identified genes similar to the
      thyA and thyB genes in several Bacillus strains by Southern hybridization and by
      DNA amplification with sequence-specific primers. Analysis of thyA genes cloned
      from B. subtilis W23 strain 2A6, B. subtilis ATCC6633, B. amyloliquefaciens S18
      and B. atrophaeus S223 reveals that they are very similar to the thyA genes from
      B. subtilis 168 and its phage phi3T, but differ considerably from the majority of
      known prokaryotic and eukaryotic thymidylate synthases.

PMID- 9648750
TI  - DAB1: a degenerate retrotransposon-like element from Neurospora crassa.
AB  - A repeated DNA sequence in the genome of Neurospora crassa has been identified as
      a family of degenerate retroelements. Retroelements encode protein sequences with
      clear homology to the reverse transcriptase, RNase H and endonuclease products of
      the pol genes common to retroviruses and retrotransposons. These sequence
      comparisons place the N. crassa element within the gypsy group of
      retrotransposons, akin to other elements found in filamentous fungi. However, the
      Neurospora element is defective, as no flanking long terminal repeats (LTRs)
      could be distinguished and the pol gene homologues contain numerous stop codons
      as a result of multiple base substitutions. The base composition of the element
      displays significant under-representation of the dinucleotide CpA, the preferred
      target site of repeat-induced point mutation (RIP). The genomic sequences exhibit
      G:C to A:T transitions between copies which are diagnostic of RIP. The degenerate
      retroelement has accordingly been designated by the acronym dab-1 (dead and
      buried).

PMID- 9648751
TI  - DNA replication is completed in Saccharomyces cerevisiae cells that lack
      functional Cdc14, a dual-specificity protein phosphatase.
AB  - The Cdc14 protein encodes a dual-specificity protein phosphatase which functions
      in late mitosis, and considerable genetic evidence suggests a role in DNA
      replication. We find that cdc14 mutants arrested in late mitosis maintain
      persistent levels of mitotic kinase activity, suggesting that Cdc14 controls
      inactivation of this kinase. Overexpression of Sicl, a cyclin-dependent protein
      kinase inhibitor, is able to suppress telophase mutants such as dbf2, cdc5 and
      cdc15, but not cdc14. It does, however, force cdc14-arrested cells into the next
      cell cycle, in which an apparently normal S phase occurs as judged by FACS and
      pulsed-field gel electrophoretic analysis. Furthermore, in a promoter shut-off
      experiment, cells lacking Cdc14 appear to carry out a normal S phase. Thus Cdc14
      functions mainly in late mitosis and it has no essential role in S phase.

PMID- 9648752
TI  - In vitro and in vivo characterization of three major dadAX promoters in
      Escherichia coli that are regulated by cyclic AMP-CRP and Lrp.
AB  - We have shown previously that the dadAX operon of Escherichia coli expresses
      multiple transcripts, which are repressed by leucine-responsive regulatory
      protein (Lrp). Here we used site-directed mutagenesis and in vitro and in vivo
      transcription assays to show that each of the three major dad transcripts
      requires a specific promoter. These promoters, P1-P3, overlap and are positively
      regulated in vivo by cyclic AMP-CRP. DNase I footprinting experiments localized
      two CRP binding sites in this region: CRP1, which is positioned upstream of P1
      P3, and CRP2, which is located within the promoters. Site-directed mutagenesis of
      each site provided evidence that CRP1 is necessary for the effects of cyclic AMP
      CRP on dad expression in vivo and in vitro, and that CRP2 probably plays little
      or no role in this process.

PMID- 9648753
TI  - Practice patterns of radiologists and nonradiologists: nationwide Medicare data
      on the performance of chest and skeletal radiography and abdominal and pelvic
      sonography.
AB  - OBJECTIVE: We assessed the relative roles of radiologists and nonradiologists in
      performing chest and skeletal radiography and nonobstetric abdominal and pelvic
      sonography. MATERIALS AND METHODS: Information was extracted from the 1993
      Medicare file on procedure volume for 65 imaging procedures. Claims were
      categorized by the specialty of the physician and the location (office or
      hospital) where the service was performed. RESULTS: In hospitals, radiologists
      performed virtually all chest and skeletal radiography and nonobstetric abdominal
      and pelvic sonography. In nonhospital settings such as offices or imaging
      centers, nonradiologists performed approximately two thirds of the chest and
      spinal radiography and nonobstetric abdominal and pelvic sonography and larger
      percentages (78-86%) of the pelvic, hip, lower extremity, and upper extremity
      radiography. CONCLUSION: Although radiologists perform virtually all chest and
      skeletal radiographs and abdominal and pelvic sonograms obtained in hospitals,
      they perform a distinct minority of these procedures in nonhospital settings. The
      data we present have certain implications for the amount of training
      nonradiologists receive in diagnostic imaging.

PMID- 9648754
TI  - Cost accounting in radiology: building a cost model using hospital-based,
      commercially available software.

PMID- 9648755
TI  - Complications of percutaneous needle biopsy.

PMID- 9648756
TI  - Radiology and medical malpractice claims: a report on the practice standards
      claims survey of the Physician Insurers Association of America and the American
      College of Radiology.

PMID- 9648757
TI  - Clinical application of a flat-panel X-ray detector based on amorphous silicon
      technology: image quality and potential for radiation dose reduction in skeletal
      radiography.
AB  - OBJECTIVE: The purpose of this study was to compare images obtained with a self
      scanning, flat-panel X-ray detector based on amorphous silicon technology with
      conventional screen-film radiographs and to evaluate the possibility of radiation
      dose reduction in skeletal radiography. SUBJECTS AND METHODS: One hundred twenty
      patients were examined prospectively using a conventional screen-film system
      (speed, 400; detector dose, 2.5 microGy) and a prototype digital amorphous
      silicon detector (simulated speed, 400 and 800, n = 120; simulated speed, 1600, n
      = 40). The resulting 400 images were evaluated independently by six radiologists
      using a subjective five-point preference scale that rated overexposure,
      underexposure, contrast resolution, spatial resolution, and soft-tissue
      presentation. Image quality was ranked on a scale from 0 to 10 according to
      subjective criteria. Statistical significance of differences was determined using
      Student's t test and confidence intervals (95% confidence level). RESULTS:
      Comparison of conventional radiographs with digital images revealed a
      statistically significant preference for the digital system for soft-tissue
      presentation (speed 400 and 800) and visualization of osteoarthrotic changes
      (speed 400). A small but statistically significant preference for conventional
      images was found with respect to contrast and spatial resolution when digital
      speed was 800 or 1600; and the visibility of arthrosis at digital speed 1600,
      osteolysis at digital speed 800 and 1600, and fractures at digital speed 1600.
      CONCLUSION: The amorphous silicon-based system with a simulated speed of 400
      provided images equivalent to screen-film radiographs. For clinical tasks such as
      routine follow-up studies, assessment of instability, or orthopedic measurements,
      a radiation dose reduction of up to 75% may be possible.

PMID- 9648758
TI  - American College of Radiology guidelines for breast cancer screening.

PMID- 9648759
TI  - The breast imaging reporting and data system: positive predictive value of
      mammographic features and final assessment categories.
AB  - OBJECTIVE: The purpose of the study was to assess the positive predictive value
      of mammographic features and final assessment categories described in the Breast
      Imaging Reporting and Data System (BI-RADS) for lesions on which biopsies have
      been performed. SUBJECTS AND METHODS: We prospectively evaluated 492 impalpable
      mammographically detected lesions on which surgical biopsy (as opposed to
      percutaneous biopsy) was performed. Each lesion was classified according to BI
      RADS descriptors for masses (margins and shape) and calcifications (morphology
      and distribution) and was categorized by the BI-RADS final assessment categories
      as category 3 ("probably benign"), category 4 ("suspicious abnormality"), or
      category 5 ("highly suggestive of malignancy"). Mammographic and pathologic
      findings were reviewed. RESULTS: Carcinoma was present in 225 (46%) of 492
      lesions. For the 492 lesions subject to biopsy, BI-RADS final assessment
      categories were category 3 in eight lesions (2%), category 4 in 355 (72%), and
      category 5 in 129 (26%). The features with highest positive predictive value for
      carcinoma were spiculated margins (81%), irregular shape (73%), linear
      calcification morphology (81%), and segmental or linear calcification
      distribution (74% and 68%, respectively). Carcinoma was present in 105 (81%) of
      129 category 5 lesions compared with 120 (34%) of 355 category 4 lesions (p <
      .001). The frequency of carcinoma was higher in category 5 than in category 4
      lesions for all mammographic lesion types and all interpreting radiologists.
      CONCLUSION: The standardized terminology of the BI-RADS lexicon allows
      quantification of the likelihood of carcinoma in an impalpable breast lesion. The
      features with highest positive predictive value--spiculated margins, irregular
      shape, linear morphology, and segmental or linear distribution--warrant
      designation of a lesion as category 5.

PMID- 9648760
TI  - Treatment issues and core needle breast biopsy: clinical context.

PMID- 9648761
TI  - Breast mass detected after blunt chest trauma.

PMID- 9648762
TI  - The Advanced Breast Biopsy Instrumentation: another Trojan horse?

PMID- 9648763
TI  - Short-interval follow-up mammography versus immediate core biopsy of benign
      breast lesions: assessment of patient stress.
AB  - OBJECTIVE: The stress experienced by women undergoing surveillance mammography
      for benign lesions was compared with that experienced by women undergoing core
      biopsy of benign lesions. MATERIALS AND METHODS: A retrospective survey was
      mailed to women in whom were diagnosed breast abnormalities that were likely to
      be benign and that were stable at short-interval follow-up mammography (n = 174)
      or in whom a core biopsy of the breast was performed, with benign findings (n =
      116). The survey included questions about stress related to the diagnostic
      experience as well as questions about who advised the women of the results of
      their breast imaging studies and about the information provided. RESULTS: Eighty
      eligible surveys were received from the women who underwent short-interval follow
      up mammography, and 58 surveys were received from the women who underwent
      biopsies. The self-reported overall stress experienced by the women who underwent
      core biopsies was significantly greater (p < .001) than that reported by the
      group who were followed up with mammography. The level of anxiety was not
      affected by the patient's perception of the probability that the lesion
      represented carcinoma. We found no significant differences in stress between
      women who discussed their mammogram results with a radiologist and women who were
      notified by their primary care provider. CONCLUSION: Short-interval follow-up
      mammography continues to be acceptable for the evaluation of lesions that are
      probably benign, even when patient anxiety is considered.

PMID- 9648764
TI  - Evaluation of needle size for breast biopsy: comparison of 14-, 16-, and 18-gauge
      biopsy needles.
AB  - OBJECTIVE: The purpose of our study was to compare the quantity and quality of
      tissue harvested from breast biopsy when using 14-, 16-, and 18-gauge "long
      throw" needles. SUBJECTS AND METHODS: We performed a prospective randomized study
      in 64 patients with 66 breast lesions. Under stereotactic guidance, passes were
      made in random order with each of the three biopsy needles in each lesion.
      Samples were measured for tissue area and scored for their quality. All lesions,
      including benign and malignant lesions and lesions with and without
      microcalcifications, were analyzed. Findings of the biopsy samples were compared
      with the final diagnoses made at surgical excision. RESULTS: In all 66 lesions,
      14-gauge biopsy needles obtained significantly larger specimens (14-gauge, 13.14
      mm2; 16-gauge, 9.6 mm2; 18-gauge, 6.41 mm2; p < .05) and scored significantly
      better (14-gauge, 8.37; 16-gauge, 7.56; 18-gauge, 7.14; p < .016) than either of
      the smaller needles. The results for malignant and benign lesions and for lesions
      with and without microcalcifications were similar but not equal to the overall
      results. However, benign lesions and areas with microcalcifications seem to be
      more problematic for both smaller needles than for 14-gauge needles. CONCLUSION:
      Our results indicate that the quantity and quality of breast biopsy specimens
      depend on the needle size. Of the three needle sizes tested, only 14-gauge long
      throw biopsy needles can be recommended for breast biopsy.

PMID- 9648765
TI  - A low-cost gelatin phantom for learning sonographically guided interventional
      breast radiology techniques.

PMID- 9648766
TI  - Coaxial core needle biopsy under mammographic guidance: indications and
      applications.

PMID- 9648767
TI  - Myofibroblastoma of the breast in women: imaging appearances.

PMID- 9648768
TI  - Acute cerebral ischemic infarction: a pathophysiologic review and radiologic
      perspective.

PMID- 9648769
TI  - Line scan diffusion imaging: characterization in healthy subjects and stroke
      patients.
AB  - OBJECTIVE: Our objective was to evaluate a new scanning method, MR line scan
      diffusion imaging, and assess the apparent diffusion coefficient in the brains of
      healthy subjects and stroke patients. SUBJECTS AND METHODS: Line scan diffusion
      imaging without cardiac gating or head restraints was implemented on low- (0.5 T)
      and medium- (1.5 T) field-strength scanners with conventional hardware. Diffusion
      weighted images were obtained in six healthy subjects and eight stroke patients.
      Unidirectional diffusion encoding was used for fast localization of stroke
      lesions. For further characterization, orthogonal diffusion encoding was applied,
      and the trace of the apparent diffusion coefficient was calculated. Single-shot
      diffusion-weighted echoplanar imaging served as the reference standard. For
      healthy subjects, imaging was repeated four times on each scanner. Mean and
      relative precision of the apparent diffusion coefficient trace values were
      calculated for each pixel. In stroke lesions and adjacent normal tissue, apparent
      diffusion coefficient trace values were determined. RESULTS: In the 108 scans
      obtained, line scan diffusion imaging proved to be robust, virtually free of
      artifact (independent of slice location and orientation), reproducible, and rapid
      for localization of a stroke. Scan time for 14 slices at 7-mm thickness was 8 min
      at 0.5 T and 7 min at 1.5 T. Image qualities with line scan diffusion imaging and
      single-shot diffusion-weighted echoplanar imaging were comparable. At 1.5 T,
      precision was essentially the same for line scan diffusion imaging (4.3%) and
      echoplanar imaging (4.7%). With line scan diffusion imaging at 0.5 T and 1.5 T,
      normal paraventricular apparent diffusion coefficient trace values averaged 0.71
      microm2/msec, and with echoplanar imaging these values averaged 0.69
      microm2/msec. In acute lesions apparent diffusion coefficient trace values were
      low, and in chronic lesions these values were high. CONCLUSION: Line scan
      diffusion imaging on low- and medium-field-strength MR scanners equipped with
      conventional hardware was reliable and practical for measuring brain apparent
      diffusion values, which can be applied to the early diagnosis, and hence timely
      management, of stroke.

PMID- 9648770
TI  - Distal neuronal degeneration caused by intracranial lesions.

PMID- 9648771
TI  - Cytomegalovirus encephalomyelitis: MR imaging findings documenting response to
      ganciclovir therapy.

PMID- 9648772
TI  - Abdominal MR angiography performed using blood pool contrast agents: comparison
      of a new superparamagnetic iron oxide nanoparticle and a linear gadolinium
      polymer.
AB  - OBJECTIVE: We evaluated and compared two different experimental blood pool
      contrast agents for abdominal MR angiography in an animal model. MATERIALS AND
      METHODS: In seven pigs, coronal T1-weighted three-dimensional fast field-echo
      images were obtained on a conventional 1.5-T MR imaging system before and after
      i.v. injection of the ultrasmall superparamagnetic iron oxide agent FeO-BPA. In
      another seven pigs, MR angiograms were acquired using the gadolinium polymer WIN
      22181. Enhanced images were obtained 5-210 min after injection of FeO-BPA and 1
      120 min after injection of WIN 22181. RESULTS: Both blood pool agents yielded
      detailed angiograms of the abdominal vascular tree when imaging lasted 2 min. In
      plane running vessels were imaged without saturation effects and with equivalent
      maximum signal-to-noise ratios. Half the maximum signal-to-noise ratio was
      reached 150 min after injection of FeO-BPA, whereas this interval was
      approximately 70 min for the gadolinium polymer. Because of these different
      imaging half-life periods, the effective diagnostic window provided by FeO-BPA
      was six to eight times longer than that of WIN 22181. In the liver, the vascular
      T1 shortening and the parenchymal T2* effect of FeO-BPA complemented each other,
      resulting in an optimal contrast-to-noise ratio significantly higher than that
      achieved with WIN 22181. This "double-contrast effect" in the liver was
      especially helpful when obtaining detailed MR portograms. CONCLUSION: The blood
      pool agents FeO-BPA and WIN 22181 can be used to produce high-quality abdominal
      MR angiograms on standard MR imaging equipment. The contrast-to-noise ratio of
      hepatic vessels is best on iron oxide-enhanced images because of a T1-T2*
      synergistic effect in the liver. The longer diagnostic window provided by FeO-BPA
      coupled with the option of in-plane imaging suggests the usefulness of FeO-BPA in
      future MR imaging-guided vascular interventions.

PMID- 9648773
TI  - Spiral MR angiography of the popliteal trifurcation.

PMID- 9648775
TI  - Treatment of inferior vena cava obstruction in hemodialysis patients using
      Wallstents: early and intermediate results.
AB  - OBJECTIVE: The purpose of this study was to evaluate the efficacy of Wallstents
      in treating inferior vena cava obstruction in hemodialysis patients. CONCLUSION:
      For the short and intermediate term, percutaneous placement of inferior vena cava
      Wallstents, followed by balloon angioplasty, is a safe and valuable technique for
      preserving the often limited central venous access in hemodialysis patients. To
      maintain patency, recurrent stenosis within the Wallstent can be treated with
      additional angioplasty.

PMID- 9648774
TI  - Aortic graft infection: the value of percutaneous drainage.
AB  - OBJECTIVE: The goal of this study was to compare patients with aortic graft
      infection treated by primary percutaneous drainage with patients who initially
      underwent surgery. MATERIALS AND METHODS: A retrospective review of 23
      consecutive patients treated for aortic graft infection was performed. Eleven
      patients were initially treated with percutaneous drainage and 12 were treated
      with surgery. The morbidity, mortality, and postprocedural reintervention rates
      and clinical outcome were analyzed for each group. RESULTS: The septic process
      resolved in nine (82%) of 11 patients treated with percutaneous drainage. Of
      these nine patients, four were treated with percutaneous drainage alone. Drainage
      was followed by removal of the infected prosthetic graft in the remaining five
      patients. In the surgical group, sepsis resolved in only four patients (33%) (p =
      .036). No periprocedural deaths occurred in the percutaneous drainage group,
      whereas six patients in the surgical group died in the perioperative period (p =
      .014). CONCLUSION: Percutaneous drainage can be used as an initial form of
      treatment in the management of aortic graft infections. Surgery after
      percutaneous drainage appears to be safer than surgery alone.

PMID- 9648776
TI  - Two-dimensional time-of-flight MR angiography of the lower extremities: artifacts
      and pitfalls.

PMID- 9648777
TI  - Preclinical evaluation and phase I clinical trial of a 99mTc-labeled synthetic
      polymer used in blood pool imaging.
AB  - OBJECTIVE: To obtain initial data on the safety and efficacy of a novel
      polymeric, synthetic blood pool contrast agent [O-monomethoxypoly(ethylene
      glycol)-O'succinyl]poly(N-epsilon-L-lysyl [99mTc]diethylenetriamine pentaacetate
      monoamide, we performed a preclinical evaluation and phase 1 clinical trial under
      an investigator-sponsored investigational new drug application. MATERIALS AND
      METHODS: Methoxypoly(ethylene glycol)ethylenetriaminopentaacetic acid was
      formulated into a kit containing the polymer, stannous chloride, and a buffer.
      Kits were stored in frozen form for subsequent labeling with technetium-99m.
      Acute and subacute toxicity studies were carried out in rats and rabbits. Healthy
      human volunteers (n = 6) were then enrolled in a prospective, open-label phase 1
      clinical study. RESULTS: Animal studies showed no signs of acute or subacute
      toxicity at doses 280 times the proposed dose for humans. In the clinical trial
      with humans, no significant abnormalities of laboratory values, ECG findings, or
      hemodynamic parameters were seen. One volunteer experienced facial flushing and
      palpitations. Four volunteers showed typical blood pool biodistribution, with a
      blood half-life of 20.6 +/- 2.3 hr. At 24 hr after administration, 22.1% +/- 2.5%
      of the injected dose had been excreted through the kidneys. Two other volunteers
      showed a different biodistribution (primarily to liver and spleen), presumably
      associated with labeling instability. CONCLUSION: Synthetic methoxypoly(ethylene
      glycol)-grafted polymers can have long circulation times in humans.
      Pharmaceuticals based on such polymers are expected to have clinical applications
      in cardiovascular imaging, gastrointestinal bleeding studies, and capillary leak
      imaging.

PMID- 9648778
TI  - Unilateral hypoperfusion or absent perfusion on pulmonary scintigraphy:
      differential diagnosis.

PMID- 9648779
TI  - Diverticulitis of the right colon revisited.

PMID- 9648780
TI  - Imaging of pancreatic transplantation using portal venous and enteric exocrine
      drainage.
AB  - OBJECTIVE: We describe the normal radiologic appearance of pancreatic allografts
      transplanted using portal venous drainage with enteric drainage of exocrine
      secretions. We also describe the radiologic appearance of postsurgical
      complications. MATERIALS AND METHODS: Of 56 patients who received pancreatic
      transplants using the portal-enteric technique, 24 patients subsequently required
      radiologic examination for suspected complications involving the pancreatic
      allograft. Twenty-three patients underwent CT scanning; a total of 58 CT scans
      were obtained. Nine abdominal sonograms were obtained in five patients, and one
      patient underwent angiography. The radiologic appearance of each transplant and
      the complications were analyzed retrospectively and correlated with the clinical
      course. RESULTS: The most common indications for CT scanning were fever, elevated
      levels of serum amylase, and evaluation or follow-up of fluid collections. CT
      showed the normal and abnormal anatomy of the allograft. Abnormal findings seen
      in the 58 CT scans included fat stranding (30 scans), ascites (21 scans),
      peripancreatic fluid or pseudocyst (13 scans), and heterogeneity of the allograft
      (five scans). One patient had pancreatic infarction with pneumatosis and
      pneumoperitoneum. The allograft was obscured by bowel gas on three sonograms.
      Four sonograms showed no abnormalities (one Doppler sonogram showed the arterial
      supply and venous drainage), and one sonogram showed a pseudocyst. In the one
      patient who underwent angiography, imaging showed no arterial blood flow to the
      transplant. CONCLUSION: Pancreatic transplantation with portal venous drainage
      and enteric drainage of exocrine secretions and the complications of such
      transplantation were revealed with CT, sonography, and angiography. Knowledge of
      normal anatomic configuration will allow proper interpretation of normal and
      abnormal findings.

PMID- 9648781
TI  - Acinar filling during secretin-stimulated MR pancreatography.
AB  - OBJECTIVE: The purpose of this study is to report a new sign, "acinar filling,"
      observed on dynamic MR pancreatography after secretin stimulation in patients
      with suspected early chronic pancreatitis. CONCLUSION: Acinar filling might
      reflect tissue hypertension or loss of pancreatic parenchyma compliance or both.
      This finding is probably an insensitive but specific sign of early chronic
      pancreatitis.

PMID- 9648782
TI  - Ductectatic mucinous cystic neoplasms of the pancreas: evaluation with MR
      cholangiopancreatography.
AB  - OBJECTIVE: We performed this study to describe the advantages of MR
      cholangiopancreatography and its findings in revealing ductectatic mucinous
      cystic neoplasms of the pancreas. CONCLUSION: MR cholangiopancreatography using
      both projection and source images can reveal characteristic findings of a
      ductectatic mucinous cystic lesion of the pancreas and show the presence of the
      communicating duct between the cystic lesion and the main pancreatic duct.

PMID- 9648783
TI  - Pancreatic pseudocyst and obstructive jaundice associated with transcaval
      penetration by a Bird's Nest vena cava filter.

PMID- 9648784
TI  - Fat in the inferior vena cava associated with caval injury.

PMID- 9648785
TI  - Color velocity imaging and power Doppler sonography of the gallbladder wall: a
      new look at sonographic diagnosis of acute cholecystitis.
AB  - OBJECTIVE: Color velocity imaging is a color sonographic technique that uses data
      contained in gray-scale B-mode image scan lines to determine blood flow velocity.
      We prospectively determined if color velocity imaging and power Doppler
      sonography can be used to differentiate acute from chronic cholecystitis. We
      analyzed the potential role of using these two color imaging techniques as an
      adjunct to conventional gray-scale sonography to differentiate acute from chronic
      cholecystitis. SUBJECTS AND METHODS: One hundred twenty-nine patients with acute
      right upper quadrant pain or clinically suspected cholecystitis underwent color
      velocity imaging and power Doppler sonography of the gallbladder as an adjunct to
      gray-scale sonography. Morphologic criteria were analyzed on gray-scale
      sonography, and the presence of flow within the gallbladder wall was assessed
      with color velocity imaging and power Doppler sonography. Imaging findings were
      compared with pathologic findings in the 50 patients who underwent
      cholecystectomy and with clinical and biologic findings in the 79 patients who
      did not undergo cholecystectomy. RESULTS: Twenty-two patients had surgically
      proven acute cholecystitis, 28 patients had surgically proven chronic
      cholecystitis, and 79 patients had no gallbladder disease. Sensitivity,
      specificity, accuracy, positive predictive value, and negative predictive value
      of gray-scale sonography for revealing acute cholecystitis were 86%, 99%, 92%,
      87%, and 97%, respectively. Sensitivity, specificity, accuracy, positive
      predictive value, and negative predictive value of color velocity imaging and
      power Doppler sonography for revealing acute cholecystitis were 95%, 100%, 99%,
      100%, and 99%, respectively. CONCLUSION: The accuracy of color velocity imaging
      and power Doppler sonography in revealing acute cholecystitis is significantly
      greater than the accuracy of gray-scale sonography.

PMID- 9648786
TI  - Percutaneous hepatic vein reconstruction for Budd-Chiari syndrome.

PMID- 9648787
TI  - Posttransplantation lymphoproliferative disorder of the liver.

PMID- 9648788
TI  - Helical CT examination of potential kidney donors.
AB  - OBJECTIVE: The purpose of our study was to evaluate helical CT using axial,
      coronal, and three-dimensional (3D) reconstruction in the examination of
      potential kidney donors and to compare the results with angiography and surgery
      when possible. We also reviewed previously published reports. SUBJECTS AND
      METHODS: Thirty-six patients underwent unenhanced and enhanced helical CT (3-mm
      collimation, 150-170 ml of i.v. contrast material injected at 4 ml/sec; pitch
      1.5; 17-sec scan delay) with coronal and 3D shaded-surface-display
      reconstructions made from 1.5-mm overlapping reconstructions. All CT scans were
      interpreted independently of each other by two observers unaware of other
      findings. A third observer, who was aware of other findings, also interpreted the
      images. Results were compared with angiography (24 cases) and surgery (24 cases).
      Our results are compared with those of other investigators. RESULTS: Axial CT was
      the best method for detecting accessory arteries (24%) and early branching (10%);
      it also detected relevant venous and ureteral anatomy and incidental findings.
      The coronal and 3D images rarely added information that resulted in changed
      patient treatment. CT findings were concordant with those of digital angiography
      in 89% of kidneys and were 98% concordant with surgery. CONCLUSION: Helical CT
      can show arterial, venous, and ureteral anatomy and can also show important
      incidental findings. If only helical CT is used, a few small accessory vessels
      and an occasional renal artery stenosis may be missed. Axial images are generally
      diagnostic and may be supplemented by multiplanar and 3D images read
      concurrently.

PMID- 9648789
TI  - Characterization of adrenal masses using unenhanced CT: an analysis of the CT
      literature.
AB  - OBJECTIVE: Unenhanced CT scanning can reliably characterize incidentally detected
      adrenal masses when observers use density measurements of the adrenal gland.
      However, controversy exists as to the optimal density threshold required to
      differentiate benign from malignant lesions. This study attempts to establish a
      consensus by performing a pooled analysis of data found in the CT literature.
      MATERIALS AND METHODS: Ten CT reports were analyzed, from which individual
      adrenal lesion density measurements were obtained for 495 adrenal lesions (272
      benign lesions and 223 malignant lesions). Threshold analysis generated a range
      of sensitivities and specificities for lesion characterization at different
      density thresholds. RESULTS: Sensitivity for characterizing a lesion as benign
      ranged from 47% at a threshold of 2 H to 88% at a threshold of 20 H. Similarly,
      specificity varied from 100% at a threshold of 2 H to 84% at a threshold of 20 H.
      CONCLUSION: The attempt to be absolutely certain that an adrenal lesion is benign
      may lead to an unacceptably low sensitivity for lesion characterization. The
      threshold chosen will depend on the patient population and the cost-benefit
      approach to patient care.

PMID- 9648790
TI  - Prostatic cancer: role of color Doppler imaging in transrectal sonography.
AB  - OBJECTIVE: The aim of this study was to assess the roles of transrectal color
      Doppler and gray-scale sonography in revealing prostatic cancer, using biopsy as
      the reference standard. SUBJECTS AND METHODS: Two hundred fifty-six patients
      referred for urologic studies underwent transrectal sonography using gray-scale
      and color Doppler scanning. All abnormal areas shown on gray-scale or color
      Doppler sonography or both were targeted and biopsies were performed. The
      patients also underwent random sextant biopsies. All biopsies were individually
      correlated with histopathologic findings and all results were analyzed. RESULTS:
      Cancer was found on biopsy in 100 patients (39%), and equivocal sonographic
      results or prostatic intraepithelial neoplasia was found in 22 other patients
      (9%). In 16 of the patients in whom cancer was detected, the tumors were
      correctly revealed only with color Doppler sonography. These 16 patients had a
      mean Gleason score of 6.4 (range, 5-8). Biopsy findings in these 16 patients
      showed eight patients with extensive lesions, three with moderate lesions, and
      five with minimal lesions. However, in nine other patients with cancer (9% of
      cancers detected), both gray-scale and color Doppler sonography failed to reveal
      lesions that were found on sextant biopsy. An analysis showed that, although
      highly sensitive, color Doppler sonography was somewhat less specific than gray
      scale sonography. CONCLUSION: Color Doppler sonography should become a routine
      part of transrectal sonography of the prostate gland to improve detection and
      targeting of lesions. The practice of performing random sextant biopsies should
      also continue.

PMID- 9648791
TI  - T2-weighted MR imaging of the uterus: comparison of optimized fast spin-echo and
      HASTE sequences with conventional fast spin-echo sequences.
AB  - OBJECTIVE: Our objective was to compare the value of a half-Fourier acquisition
      single-shot turbo spin-echo (HASTE) sequence with optimized fast spin-echo and
      conventional fast spin-echo techniques in evaluation of the uterus. SUBJECTS AND
      METHODS: Optimized fast spin-echo imaging was compared with fast spin-echo and
      HASTE imaging, for both image quality and ability to assess the zonal anatomy of
      the uterus, in 40 volunteers. In optimized fast spin-echo imaging, the imaging
      time was reduced using partial-Fourier reconstruction, reducing the echo spacing,
      and increasing the echo train length. RESULTS: HASTE imaging offered the least
      motion artifact of all techniques. On optimized fast spin-echo imaging, motion
      artifacts were moderate to severe in 10% of patients. On fast spin-echo imaging,
      motion artifacts were moderate to severe in 40% of patients. Optimized fast spin
      echo imaging was superior to the other two techniques in terms of anatomic
      sharpness and overall image quality. CONCLUSION: Although HASTE imaging offers
      the unique feature of providing images free of motion artifacts, optimized fast
      spin-echo imaging appears to be the preferred technique for T2-weighted imaging
      of the uterus.

PMID- 9648792
TI  - Salvage of the solitary kidney by insertion of a renal artery stent.
AB  - OBJECTIVE: The purpose of the study was to evaluate the use of renal artery
      stents in the solitary functioning kidney of patients who have impaired renal
      function as a result of atherosclerotic renovascular disease by assessing primary
      patency, renal function outcome, and complication rates during a mean follow-up
      period of 15 months. MATERIALS AND METHODS: The Palmaz stent was placed in the
      arteries of 21 patients with solitary functioning kidneys. All patients had
      impaired renal function (creatinine level >150 micromol/l), and four patients
      were undergoing renal dialysis. Indications for stenting were recoil after
      percutaneous transluminal angioplasty (n = 12), arterial dissection after
      angioplasty (n = 2), restenosis after angioplasty (n = 1), and as the primary
      intervention (n = 6). Follow-up angiography was performed in 16 patients (76%).
      RESULTS: Initial technical success was achieved in all patients (residual
      stenosis, <5%). At follow-up (range, 6-25 months), renal function had returned to
      normal in five patients (24%), improved in four patients (19%), stabilized in six
      patients (29%), and deteriorated in six patients (29%). Dialysis has been
      discontinued in all four dialysis patients. Major complications occurred in four
      patients (19%), including one death within 30 days of stenting. No significant
      restenoses were seen on follow-up angiography. CONCLUSION: Placement of renal
      artery stents in the solitary kidney led to benefits in 70% of patients treated,
      including improved renal function in nine patients (43%) and stabilization in six
      patients (29%). In this high-risk group of patients, we advocate renal artery
      stenting as a relatively safe procedure to salvage the solitary kidney.

PMID- 9648793
TI  - Gradient-echo versus fat-suppressed fast spin-echo MR imaging of rotator cuff
      tears.
AB  - OBJECTIVE: The purpose of this study is to compare fat-suppressed T2-weighted
      fast spin-echo sequences with T2-weighted multiplanar gradient-echo sequences in
      revealing rotator cuff disorders. MATERIALS AND METHODS: Oblique coronal fat
      suppressed fast spin-echo images and gradient-echo images of 39 patients who
      underwent surgery of the shoulder were retrospectively reviewed. Images from the
      two techniques were reviewed separately. Each set of images was interpreted twice
      by four musculoskeletal radiologists independently and without knowledge of the
      surgical findings. Sensitivity and specificity for both sequences were
      determined. The kappa statistic was used to calculate intraobserver and
      interobserver agreement of interpretations. RESULTS: For detecting any tear, the
      sensitivity of the four readers was 71-96% using fast spin-echo and 58-100% using
      gradient-echo imaging. Confidence intervals showed no difference between the two
      sequences. Sensitivity of detecting full-thickness tears was 83-100% for both
      sequences. Interobserver agreement was good. CONCLUSION: T2-weighted gradient
      echo and fat-suppressed T2-weighted fast spin-echo sequences depict rotator cuff
      tears equally well and take less time to acquire than conventional dual-echo spin
      echo sequences.

PMID- 9648794
TI  - The association between irregular greater tuberosities and rotator cuff tears: a
      sonographic study.
AB  - OBJECTIVE: Although an association between irregular greater tuberosities and
      rotator cuff tears has been suggested, no formal studies have been done. This
      study was designed to investigate the relationship between greater tuberosity
      irregularities, rotator cuff tears, and age. SUBJECTS AND METHODS: Sonographic
      examinations of both shoulders of 77 asymptomatic individuals (154 shoulders)
      between 30 and 80 years old were performed. The rotator cuffs and greater
      tuberosities were evaluated. Full- and partial-thickness rotator cuff tears were
      given equal significance. A two-tailed Fisher's exact test, a Student's t test,
      and logistic regression analysis were used to analyze the data. RESULTS:
      Sonography showed the greater tuberosity to be irregular in 36 (90%) of 40
      shoulders with a rotator cuff tear. The greater tuberosity was irregular in only
      12 (11%) of 114 shoulders without a rotator cuff tear. When the greater
      tuberosity was irregular, sonography showed 36 (75%) of 48 shoulders to have
      rotator cuff tears. When the greater tuberosity was normal, 102 (96%) of 106 of
      the rotator cuffs were normal on sonography. Statistical significance was
      detected (p < .001) for the association of greater tuberosity irregularity and
      rotator cuff tear. After accounting for age, a statistically significant
      association was found (p < .001) between rotator cuff status and greater
      tuberosity status. CONCLUSION: On sonography, greater tuberosity irregularities
      are reliable indicators in the assessment of shoulders for rotator cuff tears. In
      addition, we have shown that greater tuberosity irregularities are not simply
      related to aging.

PMID- 9648795
TI  - Anatomy, anatomic variations, and pathology of the 11- to 3-o'clock position of
      the glenoid labrum: findings on MR arthrography and anatomic sections.

PMID- 9648796
TI  - Three-dimensional MR arthrography of the shoulder: an intraarticular perspective.

PMID- 9648797
TI  - Traumatic elbow effusions in pediatric patients: are occult fractures the rule?
AB  - OBJECTIVE: Elbow joint effusion with no fracture seen on radiographs of pediatric
      patients after acute trauma has become synonymous with occult fracture. This
      study evaluates the incidence of occult fractures in such cases as determined by
      findings on follow-up radiographs. MATERIALS AND METHODS: Initial and follow-up
      radiographs were reviewed for 54 children (mean age, 7 years) with a history of
      trauma who had joint effusion but no identifiable fracture on initial
      radiographs. The presence of periosteal reaction or bony sclerosis on follow-up
      radiographs was considered to be evidence of occult fracture. Mean time between
      initial and follow-up radiographs was 18 days (range, 14-50 days). RESULTS: Only
      nine (17%) of the 54 patients showed evidence of a healing occult fracture on
      follow-up radiographs. However, we found a statistically significant relationship
      (p = .001) between persistent joint effusion on follow-up radiographs and occult
      fracture. Seventy-eight percent of cases with occult fracture, versus 16% of
      cases without occult fracture, had persistent effusions. CONCLUSION: Joint
      effusion without visualized fracture on initial radiographs after trauma does not
      correlate with the presence of occult fracture in most cases (83%). Therefore,
      joint effusion as revealed by radiography should not be considered synonymous
      with occult fracture.

PMID- 9648798
TI  - Soft-tissue hemangiomas in infants and children: diagnosis using Doppler
      sonography.
AB  - OBJECTIVE: We describe the sonographic appearance and vascularization of
      hemangiomas and determine if vessel density and peak systolic Doppler shifts
      distinguish hemangiomas from other superficial soft-tissue masses. SUBJECTS AND
      METHODS: Our pilot study included 20 infants and children with hemangiomas who
      were to undergo biopsy before treatment with interferon alpha-2b. We used Doppler
      sonography to determine the number of vessels per square centimeter, peak
      arterial Doppler shift, resistive index, and signs of arteriovenous shunting. All
      hemangiomas showed high vessel density (more than five per square centimeter) and
      high Doppler shifts (more than 2 kHz), and these two factors became our
      diagnostic criteria. A prospective study of 116 patients was then carried out.
      One hundred sixteen consecutive pediatric patients with superficial soft-tissue
      masses were examined using Doppler sonography; sonographic findings were compared
      with the final diagnoses that were established by biopsy, CT, or clinical follow
      up. RESULTS: The final diagnoses included 70 hemangiomas, 20 venous
      malformations, three arteriovenous malformations, three arteriolocapillary
      malformations, and 20 other masses. Fifty-nine lesions showing high vessel
      density (more than five per square centimeter) and a peak arterial Doppler shift
      exceeding 2 kHz were correctly diagnosed as hemangiomas (sensitivity, 84%;
      specificity, 98%). One arteriovenous malformation showed high vessel density and
      high Doppler shifts, but none of the other masses that were not hemangiomas did.
      Eleven patients with hemangiomas who were being treated with interferon at the
      time of the study fulfilled only one of the two diagnostic criteria. CONCLUSION:
      High vessel density and high peak arterial Doppler shift can be used to
      distinguish hemangiomas from other soft-tissue masses.

PMID- 9648799
TI  - Cavitary necrosis complicating pneumonia in children: sequential findings on
      chest radiography.
AB  - OBJECTIVE: The objective of this study was to describe the sequential clinical
      and radiographic findings of cavitary necrosis complicating pneumonia in
      childhood. MATERIALS AND METHODS: A study group of 17 children (mean age, 6
      years) was identified by reviewing CT examinations of all patients who underwent
      CT of the chest to evaluate possible complications of pneumonia over a 3-year
      period. Children included in the study group were those who met the criteria for
      cavitary necrosis: loss of lung architecture, decreased enhancement, and multiple
      cavities with thin, nonenhancing walls. In the 17 identified cases, sequential
      chest radiographs were reviewed for visibility of a lung cavity. Long-term follow
      up radiographs were evaluated for persistent abnormalities. RESULTS: Ten of the
      17 cases of cavitary necrosis seen on CT showed cavities at some time on
      radiography: one cavity was visible at the time of diagnosis on CT and nine were
      visible only later. All three cavities that were predominantly air-filled on CT
      were revealed by radiography, whereas 50% (7/14) of predominantly fluid-filled
      cavities were revealed by radiography. Eleven children underwent follow-up
      radiography more than 40 days after the diagnosis of cavitary necrosis.
      Radiographs of those 11 children showed clear lungs without pulmonary sequelae.
      CONCLUSION: In children, cavitary necrosis is associated with severe illness;
      however, cases usually resolve without surgical intervention, and long-term
      follow-up radiography shows clear lungs without pulmonary sequelae. Evidence of
      cavitary necrosis complicating pneumonia is often seen on CT before or in the
      absence of findings on chest radiography.

PMID- 9648800
TI  - Radiologic placement of long-term subcutaneous venous access ports in children.
AB  - OBJECTIVE: The purpose of this study was to review the results of radiologically
      placed subcutaneous venous access ports in a pediatric population requiring long
      term venous access. CONCLUSION: Sixteen of 20 patients had no significant
      problems with their ports. In the pediatric population, radiologically placed
      subcutaneous venous access ports offer a high success rate, a low complication
      rate, and significant cost savings over surgically placed ports.

PMID- 9648801
TI  - Hemoptysis during lung biopsy after aspirin.

PMID- 9648802
TI  - Bone marrow abnormalities revealed by MR imaging.

PMID- 9648803
TI  - Callback rate after screening mammography.

PMID- 9648804
TI  - T2-weighted fast spin-echo MR imaging of liver.

PMID- 9648805
TI  - Ketamine hydrochloride for interventional radiology in children: is it sedation
      or anesthesia by the radiologist?

PMID- 9648806
TI  - The "R" word: unfortunately, the mammography war is not yet over.

PMID- 9648807
TI  - Reducing headaches after a myelogram.

PMID- 9648808
TI  - Current concepts in osteoporosis: theoretic rather than practical.

PMID- 9648809
TI  - Can patient retention of rectal barium be guaranteed?

PMID- 9648810
TI  - Problematic p values.

PMID- 9648811
TI  - Concerning the National Breast and Cervical Cancer Early Detection Program.

PMID- 9648812
TI  - Metallic particles on mammography.

PMID- 9648813
TI  - Epidermoid cyst in an intrapancreatic accessory spleen: CT and pathologic
      findings.

PMID- 9648814
TI  - Helical CT of a patient with suspected renal colic: a new protocol consideration.

PMID- 9648815
TI  - Extensive esophageal pneumatosis after acute dilatation of the stomach.

PMID- 9648816
TI  - Term pregnancy in a patient with McKusick-Kaufman syndrome.

PMID- 9648817
TI  - Multicentric granulocytic sarcoma of the breast: mammographic and sonographic
      findings.

PMID- 9648818
TI  - Neurosarcoidosis mimicking a cerebellopontine angle meningioma.

PMID- 9648819
TI  - Endovascular retrieval of an embolized central venous catheter in a neonate of
      very low birth weight.

PMID- 9648820
TI  - Autonomic mediation of glucagon secretion during hypoglycemia: implications for
      impaired alpha-cell responses in type 1 diabetes.
AB  - This article examines the role of the autonomic nervous system in mediating the
      increase of glucagon secretion observed during insulin-induced hypoglycemia
      (IIH). In the first section, we briefly review the importance of the alpha-cell
      response in recovery from hypoglycemia under both physiologic conditions and
      pathophysiologic conditions, such as type 1 diabetes. We outline three possible
      mechanisms that may contribute to increased glucagon secretion during
      hypoglycemia but emphasize autonomic mediation. In the second section, we review
      the critical experimental data in animals, nonhuman primates, and humans
      suggesting that, in the absence of diabetes, the majority of the glucagon
      response to IIH is mediated by redundant autonomic stimulation of the islet alpha
      cell. Because the glucagon response to hypoglycemia is often impaired in patients
      with type 1 diabetes, in the third section, we examine the possibility that
      autonomic impairment contributes to the impairment of the glucagon response in
      these patients. We review two different types of autonomic impairment. The first
      is a slow-onset and progressive neuropathy that worsens with duration of
      diabetes, and the second is a rapid-onset, but reversible, autonomic dysfunction
      that is acutely induced by antecedent hypoglycemia. We propose that both types of
      autonomic dysfunction can contribute to the impaired glucagon responses in
      patients with type 1 diabetes. In the fourth section, we relate restoration of
      these glucagon responses to restoration of the autonomic responses to
      hypoglycemia. Finally, in the fifth section, we summarize the concepts underlying
      the autonomic hypothesis, the evidence for it, and the implications of the
      autonomic hypothesis for the treatment of type 1 diabetes.

PMID- 9648821
TI  - Constitutive activation of protein kinase B alpha by membrane targeting promotes
      glucose and system A amino acid transport, protein synthesis, and inactivation of
      glycogen synthase kinase 3 in L6 muscle cells.
AB  - Phosphatidylinositol 3-kinase (PI 3-kinase) has been implicated in the regulation
      of numerous cellular processes, including the insulin-induced regulation of
      glycogen synthase kinase 3 (GSK-3) and glucose transport. The hormonal-induced
      inactivation of GSK-3 is mediated by protein kinase B (PKB), a downstream target
      of PI 3-kinase, whose involvement in other insulin-stimulated responses remains
      poorly defined at present. In this study, we investigated whether the uptake of
      glucose, system A amino acid transport, and cellular protein synthesis are
      regulated by PKBalpha in L6 skeletal muscle cells. L6 cells stably overexpressing
      wild-type PKBalpha (wtPKBalpha) or a constitutively active membrane-targeted
      PKBalpha (mPKBalpha) showed a 3- and 15-fold increase in PKB activity,
      respectively. Both wtPKBalpha and mPKBalpha expression led to a significant
      increase in the basal uptake of glucose and methyl-aminoisobutyric acid (a
      substrate for the system A amino acid transporter), at least to a level seen in
      control cells treated with insulin. The stimulation in glucose transport was
      facilitated, in part, by the increased translocation of GLUT4 to the plasma
      membrane and also through an increase in the cellular synthesis of GLUT3. In the
      absence of insulin, only muscle cells expressing the constitutively active
      PKBalpha showed a significant increase in protein synthesis and an inhibition in
      GSK-3. Our results indicate that constitutive activation of PKBalpha in skeletal
      muscle stimulates the uptake of glucose, system A amino acids, and protein
      synthesis and promotes the inactivation of GSK-3. These observations imply that
      PKBalpha may have a role in the insulin-regulated control of these processes in
      skeletal muscle.

PMID- 9648822
TI  - Chronic central leptin infusion enhances insulin-stimulated glucose metabolism
      and favors the expression of uncoupling proteins.
AB  - Continuous (4 days) intracerebroventricular leptin infusion (12 microg/day) was
      performed in lean rats, and its hormonometabolic effects were determined.
      Intracerebroventricular leptin administration did not result in leakage of the
      hormone into the peripheral circulation. Thus, its effects were elicited by its
      presence within the central nervous system. Intracerebroventricular leptin
      infusion produced marked decreases in food intake and body weight gain relative
      to vehicle-infused fed ad libitum rats. Because decreases in food intake alter
      hormonometabolic homeostasis, additional control rats pair-fed to the amount of
      food consumed by leptin-infused ones were included in the study.
      Intracerebroventricular leptin-infused and vehicle-infused pair-fed rats were
      characterized, relative to vehicle-infused ad libitum-fed animals, by decreases
      in body weight and insulinemia and by increases in insulin-stimulated overall
      glucose utilization and muscle and brown adipose tissue glucose utilization
      index. Brown adipose tissue uncoupling protein (UCP)1, UCP2, and UCP3 mRNA levels
      were markedly decreased in pair-fed animals relative to those of fed ad libitum
      control animals, as were liver and white adipose tissue UCP2 and muscle UCP3 mRNA
      levels. In marked contrast, intracerebroventricular leptin administration was
      accompanied by the maintenance of high UCP1, UCP2, and UCP3 expression in all
      these tissues. Thus, despite analogies between leptin's effects and those of pair
      feeding with regard to glucose handling, their respective underlying mechanisms
      differ. While leptin maintains or favors energy-dissipating mechanisms (UCP1,
      UCP2, and UCP3), the latter are markedly depressed in pair-fed rats. This effect
      of leptin may prevent subsequent excessive storage processes, thereby maintaining
      normal body homeostasis.

PMID- 9648823
TI  - Glucose turnover and insulin sensitivity in rats with pancreatic islet
      transplants.
AB  - To study the metabolic effects of insulin derived from islet grafts, oral glucose
      tolerance (OGT) and glucose turnover were examined in streptozotocin-induced
      diabetic Lewis rats rendered normoglycemic by syngeneic islet grafts in the renal
      subcapsular space (REN), in REN with renal vein-to-mesenteric vein anastomosis
      (REN-RMA), in the liver (intrahepatic [IH]), or in a parahepatic omental pouch
      (POP) and compared with normal rats. Normal OGT was found at 1 month
      posttransplant in all animals receiving approximately 3,000 islets, with
      hyperinsulinemic responses in the REN group compared with the other groups, and
      with higher C-peptide responses in the IH group than in the other groups (P <
      0.05 by one-way analysis of variance). Glucose turnover studies in the insulin
      stimulated steady state (INS-SS; infusion of insulin at 10 pmol x kg(-1) x min(
      1)) at 2 months posttransplant showed that whole body glucose disappearance rates
      (Rd) were similar in all groups, but the REN group had higher steady-state
      insulin levels than the other groups. Glucose infusion rates (GIRs) were lower in
      the REN and IH groups than in the other groups. Apparent endogenous glucose
      production (EGP) was not completely inhibited in the REN and IH groups, while
      complete inhibition was observed in the other groups. When INS-SS insulin levels
      were matched to the level in REN rats by increasing the insulin infusion rate to
      20 pmol x kg(-1) x min(-1) in REN-RMA, IH, and normal rats, GIR and Rd were
      elevated, exceeding those values in REN rats, but GIR in IH rats was still lower
      than in REN-RMA and normal rats. Thus, 1) in the REN group, impairment of
      inhibition of EGP and of stimulation of Rd by exogenous insulin contribute to
      insulin resistance; 2) in the IH group, incomplete inhibition of EGP is the major
      determinant of insulin resistance; and 3) with portal delivery of insulin in the
      REN-RMA and POP groups, normal insulin sensitivity is preserved. The present
      study confirms that hepatic portal delivery of islet secretions is necessary for
      physiological regulation of glucose metabolism. The study also suggests the IH
      grafts do not provide physiological regulation of glucose metabolism, raising the
      question of whether the liver is an appropriate site for insulin-secreting tissue
      replacement therapy in diabetes.

PMID- 9648824
TI  - Measurements of oxygen tension in native and transplanted rat pancreatic islets.
AB  - This study was performed to measure the oxygen tension before and after
      revascularization of pancreatic islets transplanted beneath the renal capsule and
      to investigate to what extent this was affected by acute and chronic
      hyperglycemia. In addition, the oxygen tension in islets within the pancreas was
      determined. PO2 was measured with a modified Clark electrode (tip 2-6 microm
      o.d.). Within native pancreatic islets, the mean PO2 was higher (31-37 mmHg) than
      within the exocrine pancreas (20-23 mmHg). The mean oxygen tension in the
      transplanted islets the day after implantation was half of that recorded in
      native islets (14-19 mmHg) and did not differ between normoglycemic and diabetic
      recipients. At 1 month after transplantation, when revascularization had
      occurred, the mean PO2 in the islet grafts was 9-15 mmHgf in normoglycemic
      animals but was lower (6-8 mmHg) in diabetic animals, whereas the blood perfusion
      of the transplants, as measured with laser-Doppler flowmetry (probe diameter 0.45
      mm), was similar in both groups. The mean oxygen tension in the superficial renal
      cortex surrounding the implanted islets was similar in all groups and remained
      stable at 13-21 mmHg. Intravenous administration of D-glucose (1 g/kg) did not
      affect the oxygen tension in any of the investigated tissues. We conclude that
      the mean PO2 in islets implanted under the renal capsule is markedly lower than
      in native islets, not only in the immediate posttransplantation period but also 1
      month after implantation, i.e., when revascularization has occurred. Furthermore,
      persistent hyperglycemia in the recipient leads to a further decrease in graft
      oxygen tension. To what extent this may contribute to islet graft failure is at
      present unknown.

PMID- 9648825
TI  - Sex difference in resistance to dexamethasone-induced apoptosis in NOD mice:
      treatment with 1,25(OH)2D3 restores defect.
AB  - The NOD mouse, a model for type 1 diabetes, is characterized by resistance to
      apoptosis in immunocytes. The aim of this study was to investigate a link between
      apoptosis in NOD thymocytes and autoimmunity. First, we demonstrated that the
      sexual dimorphism in diabetes incidence in NOD mice (females are more diabetes
      prone than males) is reflected by differences in apoptosis. Apoptosis in NOD
      thymocytes, 24 h after dexamethasone, was decreased in both sexes compared with
      C57B1/6, but it was lower in female mice (26 +/- 2%) than in male mice (50 +/-
      3%, P < 0.001). Further, we demonstrated that sex hormones themselves play a
      central role in this difference, since castration of NOD male mice, which
      increases diabetes incidence, decreased apoptosis levels (32 +/- 2%), while
      treatment of NOD female mice with dihydrotestosterone, which protects against
      diabetes, restored apoptosis to male levels (42 +/- 1.5%). Finally, we
      demonstrated that 1,25-dihydroxyvitamin D3, a steroid hormone that prevents
      diabetes in NOD mice, restored apoptosis levels to C57B1/6 reference levels. This
      improved apoptosis was seen in male (68 +/- 1 vs. 50 +/- 3% in untreated NOD
      mice, P < 0.001) but especially in female NOD mice (51 +/- 5 vs. 26 +/- 2% in
      untreated NOD mice, P < 0.001). Fluorescence-activated cell sorter analysis of
      thymocyte subsets revealed marked differences, especially in CD4+CD8+ and CD4+
      cells. We conclude that the sexual dimorphism in diabetes incidence in NOD mice
      is paralleled by a dimorphism in resistance to apoptotic signals in NOD
      thymocytes. This resistance to apoptosis is driven by sex hormones and is
      corrected by 1,25-dihydroxyvitamin D3.

PMID- 9648826
TI  - Peptones stimulate both the secretion of the incretin hormone glucagon-like
      peptide 1 and the transcription of the proglucagon gene.
AB  - Truncated glucagon-like peptide (GLP)-1 is a potent incretin. Its synthesis and
      secretion are modulated by food, but the influence of individual nutrients
      remains to be established. The hypothesis that protein hydrolysates (peptones)
      can directly regulate both GLP-1 secretion and proglucagon (PG) gene
      transcription was tested in this study, ex vivo in the isolated vascularly
      perfused rat intestine and in vitro in the murine enteroendocrine cell line STC
      1. Peptones were albumin egg hydrolysate (AEH) and meat hydrolysate (MH). We
      demonstrate in these two models that peptones dose-dependently stimulate GLP-1
      release, whereas isocaloric quantities of bovine serum albumin or of an amino
      acid mixture had no stimulatory effect. A strong and rapid increase of PG RNA
      level was observed in STC-1 cells treated with peptones (14-fold and 7-fold
      increase after 4 h of incubation with 3% wt/vol MH and AEH, respectively).
      Peptones also increased the PG RNA level in the colonic PG-expressing cell line
      GLUTag. In contrast, peptones did not modify the PG RNA level in two pancreatic
      glucagon-producing cell lines, namely, the RINm5F and INR1G9 cells. The peptone
      effect in STC-1 cells was completely abolished by blocking transcription before
      MH treatment. The stability of proglugacon transcripts was not modified by MH
      treatment, but nascent transcripts were more abundant in STC-1 cells preincubated
      with MH. Finally, MH treatment strongly stimulated (15-fold stimulation) the
      transcriptional activity of two PG gene promoter fragments (-1100 and -350 base
      pair) linked to the CAT reporter gene transiently transfected in STC-1 cells.
      Overall, peptones evoke an as yet undescribed release of GLP-1 when brought into
      contact with native intestinal L-cells or with STC-1 enteroendocrine cells. The
      increased transcription of the glucagon gene in the latter system suggests an
      important role of protein hydrolysates in the control of not only the secretion
      but also the synthesis of the incretin hormone.

PMID- 9648827
TI  - Enhanced glucose-dependent insulinotropic polypeptide secretion and
      insulinotropic action in glucagon-like peptide 1 receptor -/- mice.
AB  - Incretins are gastrointestinal hormones that act on the pancreas to potentiate
      glucose-stimulated insulin secretion. Despite the physiological importance of the
      enteroinsular axis, disruption of glucagon-like peptide (GLP)-1 action is
      associated with only modest glucose intolerance in GLP-1 receptor -/- (GLP-1R -/
      ) mice. We show here that GLP-1R -/- mice exhibit compensatory changes in the
      enteroinsular axis via increased glucose-dependent insulinotropic polypeptide
      (GIP) secretion and enhanced GIP action. Serum GIP levels in GLP-1R -/- mice were
      significantly elevated versus those in +/+ control mice after an oral glucose
      tolerance test (369 +/- 40 vs. 236 +/- 28 pmol/l; P < or = 0.02). Furthermore,
      GIP perfusion of mice pancreas and isolated islets in the presence of elevated
      glucose concentrations elicited a significantly greater insulin response in GLP
      1R -/- than in +/+ mice (P < or = 0.02-0.05). In contrast, no significant
      perturbation in the insulin response to perfused glucagon was detected under
      conditions of low (4.4 mmol/l) or high (16.6 mmol/l) glucose in GLP-1R -/- mice.
      Total pancreatic insulin but not glucagon content was significantly reduced in
      GLP-1R -/- compared with in +/+ mice (77 +/- 9 vs. 121 +/- 10 pmol/mg protein; P
      < or = 0.005). These observations suggest that upregulation of the GIP component
      of the enteroinsular axis, at the levels of GIP secretion and action, modifies
      the phenotype resulting from interruption of the insulinotropic activity of GLP-1
      in vivo.

PMID- 9648829
TI  - Pancreatic beta-cell regeneration after 48-h glucose infusion in mildly diabetic
      rats is not correlated with functional improvement.
AB  - We investigated the effect of glucose infusion on beta-cell regeneration in rats
      made mildly diabetic by a single injection of low dosage (35 mg/kg)
      streptozotocin (STZ). Nondiabetic (ND) and STZ rats were submitted to a 48-h
      glucose infusion (hyperglycemia approximately 22 mmol/l in both groups: ND and
      STZ hyperglycemic-hyperinsulinemic [ND HG-HI and STZ HG-HI rats]). Before
      infusion, beta-cell mass was 65% lower in STZ rats than in ND rats (2.0 +/- 0.02
      vs. 5.5 +/- 0.6 mg), 1.6-fold increased in ND HG-HI rats (8.7 +/- 1.7 mg), and
      2.7-fold increased in STZ HG-HI rats (5.4 +/- 0.9 mg). In ND HG-HI rats, beta
      cell enlargement was related to an increase in beta-cell responsiveness to
      nutrient secretagogues both in vivo and in vitro, whereas in STZ HG-HI rats, no
      significant improvement in insulin secretion could be noticed. To determine the
      respective role of hyperglycemia and hyperinsulinemia on beta-cell area changes,
      ND and STZ rats were submitted to a 48-h hyperinsulinemic-euglycemic clamp. No
      modification of beta-cell mass was detected in either group. In conclusion, 48-h
      superimposed hyperglycemia was enough to restore beta-cell mass previously
      reduced by STZ injection. This effect seemed to be due to hyperglycemia rather
      than hyperinsulinemia alone. The data stress the dissociation between beta-cell
      regeneration and improvement in islet function in diabetic rats. Our model seems
      suitable for studying factors that can improve the plasticity and function of the
      pancreas in NIDDM.

PMID- 9648828
TI  - Glucose augmentation of mastoparan-stimulated insulin secretion in rat and human
      pancreatic islets.
AB  - Mastoparan, a tetradecapeptide component of wasp venom, activates heterotrimeric
      G-proteins and stimulates exocytosis in several cell types, including the
      pancreatic beta-cell. In this study, its effects on insulin secretion were
      assessed in both rat and human pancreatic islets, along with the ability of
      glucose and alpha-ketoisocaproate (alpha-KIC) to augment mastoparan-stimulated
      release. In Ca2+-free Krebs-Ringer bicarbonate buffer containing 2.8 mmol/l
      glucose, 20 micromol/l mastoparan stimulated insulin secretion 12- and 14-fold in
      rat and human islets, respectively. The inactive analog mastoparan-17 had no
      effect on release. Under the same Ca2+-free conditions, 11.1 mmol/l glucose had
      no effect on insulin release alone, but augmented mastoparan-stimulated release
      by 74% in both rat and human islets. Stimulation of release by mastoparan and
      augmentation of release by glucose were unaffected by treatment with pertussis
      toxin. The effect of cellular GTP depletion on the mastoparan stimulation of
      release and augmentation by alpha-KIC was studied by culturing rat islets in the
      presence of 25 microg/ml mycophenolic acid for 20 h. In the control islets, alpha
      KIC augmented mastoparan-stimulated insulin release by 80%. In the GTP-depleted
      rat islets, mastoparan-stimulated insulin release was not changed, while the
      augmentation by alpha-KIC was eliminated. Mannoheptulose completely blocked the
      augmentation by glucose. In conclusion, mastoparan stimulates insulin release by
      activation of a signal transduction pathway that can be augmented by nutrients
      such as glucose and alpha-KIC. Nutrient augmentation of this pathway is heavily
      dependent on GTP.

PMID- 9648830
TI  - A role for Ca2+-sensitive nonselective cation channels in regulating the membrane
      potential of pancreatic beta-cells.
AB  - The incretin hormones, glucagon-like peptide 1 and pituitary adenylyl cyclase
      activating polypeptide, are proposed to activate a maitotoxin (MTX)-sensitive,
      Ca2+-dependent nonselective cation current in pancreatic beta-cells and
      insulinoma cells. This MTX-sensitive current is present in human beta-cells as
      well as in mouse and rat beta-cells, and is accompanied by a rise in cytosolic
      Ca2+ in voltage-clamped cells in which the activation of voltage-dependent Ca2+
      channels is prevented. Activation of the nonselective cation current is inhibited
      by reduction of disulfide bonds with intracellular, but not extracellular,
      dithiothreitol, and is also abolished by intracellular dialysis with trypsin. The
      nonselective cation channels that carry this current have a conductance of about
      30 pS, with Na+ as the major extracellular cation. We estimate that these cation
      channels are expressed on beta-cells at a density similar to that of ATP
      sensitive potassium channels (K(ATP) channels) and exhibit spontaneous activity
      at basal glucose concentrations. We propose that this spontaneous cation channel
      activity constitutes at least part of the depolarizing background conductance
      that permits changes in the activity of K(ATP) channels to regulate the resting
      potential of beta-cells.

PMID- 9648831
TI  - A specific increased expression of insulin receptor substrate 2 in pancreatic
      beta-cell lines is involved in mediating serum-stimulated beta-cell growth.
AB  - Certain nutrients and growth factors can stimulate pancreatic beta-cell growth.
      However, the appropriate mitogenic signaling pathways in beta-cells have been
      relatively undefined. In this study, differential gene expression in NEDH rat
      insulinoma was compared with NEDH rat primary islet beta-cells. Differential mRNA
      display analysis revealed an elevated expression in insulinoma of VL30
      transposons, S24 ribosomal protein, and cytochrome-C oxidaseVIIc that is typical
      for cells undergoing mitosis. A gene candidate approach revealed that mRNA levels
      of the oncogenes c-fos and c-jun were equivalently expressed in insulinoma and
      islet cells, as was the mRNA for the mitogenic signal transduction molecule
      insulin receptor substrate (IRS)-1. However, in contrast to that of IRS-1, IRS-2
      gene expression was 60- to 70-fold higher in the insulinoma tissue compared with
      islets, which was reflected at the protein as well as the mRNA level. The
      specific elevated IRS-2 expression was a consistent observation across all rodent
      pancreatic beta-cell lines. To investigate whether IRS-2 was functional, serum
      stimulated beta-cell proliferation was examined in isolated insulinoma cells.
      After a 48-h period of serum withdrawal, 24 h of serum refeeding rendered an 8-
      to 10-fold increase in [3H]thymidine incorporation into insulinoma cells. This
      serum-stimulated DNA synthesis was prevented by inhibitors of tyrosine protein
      kinase and phosphatidylinositol (PI) 3-kinase activities, as well as the
      activation of mitogen-activated protein (MAP) kinase and p70S6K. Examination of
      IRS-mediated signal transduction pathways indicated that after 10-15 min of serum
      refeeding, there was increased tyrosine phosphorylation of IRS-2 and pp60, and PI
      3-kinase recruitment to IRS-2. Serum also increased the association of growth
      factor-bound protein 2/murine sons of sevenless 1 protein to a PI 3-kinase/IRS-2
      protein complex. Moreover, serum also activated MAP-kinase (erk-1 and erk-2
      isoforms) and 70 kD S6 kinase. Thus IRS-mediated signal transduction pathways are
      functional in pancreatic beta-cells. It is conceivable that IRS-2 expression in
      beta-cells contributes to maintaining the islet beta-cell population,
      complementary to observations in the IRS-2 knockout mouse in which beta-cell mass
      is markedly reduced.

PMID- 9648832
TI  - Long-term exposure of beta-INS cells to high glucose concentrations increases
      anaplerosis, lipogenesis, and lipogenic gene expression.
AB  - Chronic exposure of pancreatic beta-cells to high glucose has pleiotropic action
      on beta-cell function. In particular, it induces key glycolytic genes, promotes
      glycogen deposition, and causes beta-cell proliferation and altered insulin
      secretion characterized by sensitization to low glucose. Postglycolytic events,
      in particular, anaplerosis and lipid signaling, are thought to be implicated in
      beta-cell activation by glucose. To understand the biochemical nature of the beta
      cell adaptive process to hyperglycemia, we studied the regulation by glucose of
      lipogenic genes in the beta-cell line INS-1. A 3-day exposure of cells to
      elevated glucose (5-25 mmol/l) increased the enzymatic activities of fatty acid
      synthase 3-fold, acetyl-CoA carboxylase 30-fold, and malic enzyme 1.3-fold.
      Pyruvate carboxylase and citrate lyase expression remained constant. Similar
      observations were made at the protein and mRNA levels except for malic enzyme
      mRNA, which did not vary. Metabolic gene expression changes were associated with
      chronically elevated levels of citrate, malate, malonyl-CoA, and conversion of
      glucose carbon into lipids, even in cells that were subsequently exposed to low
      glucose. Similarly, fatty acid oxidation was suppressed and phospholipid and
      triglyceride synthesis was enhanced independently of the external glucose
      concentration in cells preexposed to high glucose. The results suggest that a
      coordinated induction of glycolytic and lipogenic genes in conjunction with
      glycogen and triglyceride deposition, as well as increased anaplerosis and
      altered lipid partitioning, contribute to the adaptive process to hyperglycemia
      and glucose sensitization of the beta-cell.

PMID- 9648833
TI  - Elevated PC-1 content in cultured skin fibroblasts correlates with decreased in
      vivo and in vitro insulin action in nondiabetic subjects: evidence that PC-1 may
      be an intrinsic factor in impaired insulin receptor signaling.
AB  - Membrane glycoprotein PC-1 inhibits insulin receptor (IR) tyrosine kinase
      activity and subsequent cellular signaling. PC-1 content is elevated in muscle
      and adipose tissue from insulin-resistant subjects, and its elevation correlates
      with in vivo insulin resistance. To determine whether elevated PC-1 content is a
      primary cause of insulin resistance, we have now measured PC-1 content in
      cultured skin fibroblasts from nonobese nondiabetic insulin-resistant subjects
      and found that 1) PC-1 content was significantly higher in these cells when
      compared with cells from insulin-sensitive subjects (6.7 +/- 0.9 vs. 3.1 +/- 0.6
      ng/0.1 mg protein, mean +/- SE, P < 0.01); 2) PC-1 content in fibroblasts was
      highly correlated with PC-1 content in muscle tissue (r = 0.95, P = 0.01); 3) PC
      1 content in fibroblasts negatively correlated with both decreased in vivo
      insulin sensitivity and decreased in vitro IR autophosphorylation; and 4) in
      cells from insulin-resistant subjects, insulin stimulation of glycogen synthetase
      was decreased. These studies indicate, therefore, that the elevation of PC-1
      content may be a primary factor in the cause of insulin resistance.

PMID- 9648834
TI  - Renal lactate metabolism and gluconeogenesis during insulin-induced hypoglycemia.
AB  - The contribution of gluconeogenic precursors to renal glucose production (RGP)
      during insulin-induced hypoglycemia was assessed in conscious dogs. Ten days
      after surgical placement of sampling catheters in the right and left renal veins
      and femoral artery and an infusion catheter in the left renal artery, systemic
      and renal glucose and glycerol kinetics were measured with peripheral infusions
      of [6-3H]glucose and [2-13C]glycerol. Renal blood flow was determined with a
      flowprobe, and the renal balance of lactate, alanine, and glycerol was calculated
      by arteriovenous difference. After baseline, six dogs received 2-h simultaneous
      infusions of peripheral insulin (4 mU x kg(-1) x min(-1)) and left intrarenal
      [6,6-2H]dextrose (14 micromol x kg(-1) x min(-1)) to achieve and maintain left
      renal normoglycemia during systemic hypoglycemia. Arterial glucose decreased from
      5.3 +/- 0.1 to 2.2 +/- 0.1 mmol/l; insulin increased from 46 +/- 5 to 1,050 +/-
      50 pmol/l; epinephrine, from 130 +/- 8 to 1,825 +/- 50 pg/ml; norepinephrine,
      from 129 +/- 6 to 387 +/- 15 pg/ml; and glucagon, from 52 +/- 2 to 156 +/- 12
      pg/ml (all P < 0.01). RGP increased from 1.7 +/- 0.4 to 3.0 +/- 0.5 (left) and
      from 0.6 +/- 0.2 to 3.2 +/- 0.2 (right) micromol x kg(-1) x min(-1) (P < 0.01).
      Whole-body glycerol appearance increased from 6.0 +/- 0.5 to 7.7 +/- 0.7 micromol
      x kg(-1) x min(-1)(P < 0.01); renal conversion of glycerol to glucose increased
      from 0.13 +/- 0.04 to 0.30 +/- 0.10 (left) and from 0.11 +/- 0.03 to 0.25 +/-
      0.05 (right) micromol x kg(-1) x min(-1), (P < 0.05). Net renal gluconeogenic
      precursor uptake increased from 1.5 +/- 0.4 to 5.0 +/- 0.4 (left) and from 0.9 +/
      0.2 to 3.8 +/- 0.4 (right) micromol x kg(-1) x min(-1) (P < 0.01). Renal lactate
      uptake could account for approximately 40% of postabsorptive RGP and for 60% of
      RGP during hypoglycemia. These results indicate that gluconeogenic precursor
      extraction by the kidney, particularly lactate, is stimulated by
      counterregulatory hormones and accounts for a significant fraction of the
      enhanced gluconeogenesis induced by hypoglycemia.

PMID- 9648835
TI  - Regulation of skeletal muscle hexokinase II by insulin in nondiabetic and NIDDM
      subjects.
AB  - Impaired muscle glucose phosphorylation to glucose-6-phosphate by hexokinases
      (HKs)-I and -II may contribute to insulin resistance in NIDDM and obesity. HK-II
      expression is regulated by insulin. We tested the hypothesis that basal and
      insulin-stimulated expression of HK-II is decreased in NIDDM and obese subjects.
      Skeletal muscle HK-I and HK-II activities were measured in seven lean and six
      obese normal subjects and eight patients with NIDDM before and at 3 and 5 h of a
      hyperinsulinemic (80 mU x m(-2) x min(-1)) euglycemic clamp. To assess whether
      changes in HK-II expression seen during a glucose clamp are likely to be
      physiologically relevant, we also measured HK-I and HK-II activity in 10 lean
      normal subjects before and after a high-carbohydrate meal. After an overnight
      fast, total HK, HK-I, and HK-II activities were similar in lean and obese control
      subjects; but HK-II was lower in NIDDM patients than in lean subjects (1.42 +/-
      0.16 [SE] vs. 2.33 +/- 0.24 nmol x min(-1) x mg(-1) molecular weight, P < 0.05)
      and accounted for a lower proportion of total HK (33 +/- 3 vs. 47 +/- 3%, P <
      0.025). HK-II (but not HK-I) activity increased during the clamp in lean and
      obese subjects by 34 and 36% after 3 h and by 14 and 22% after 5 h of
      hyperinsulinemia; no increase was found in the NIDDM patients. In the lean
      subjects, muscle HK-II activity also increased by 15% 4 h after the meal, from
      2.47 +/- 0.19 basally to 2.86 +/- 0.28 nmol x min(-1) x mg(-1) protein (P <
      0.05). During the clamps, muscle HK-II activity correlated with muscle citrate
      synthase activity in the normal subjects (r = 0.58, P < 0.05) but not in the
      NIDDM patients. A weak relationship was noted between muscle HK-II activity and
      glucose disposal rate at the end of the clamp when all three groups were combined
      (r = 0.49, P < 0.05). In summary, NIDDM patients have lower muscle HK-II activity
      basally and do not increase the activity of this enzyme in response to a 5-h
      insulin stimulus. This defect may contribute to their insulin resistance. In
      nondiabetic obese subjects, muscle HK-II expression and its regulation by insulin
      are normal.

PMID- 9648836
TI  - Aminoguanidine inhibits reactive oxygen species formation, lipid peroxidation,
      and oxidant-induced apoptosis.
AB  - Aminoguanidine (AG) treatment, like nerve growth factor (NGF) treatment, prevents
      diabetes-induced apoptosis of retinal Muller cells in the rat eye, but the
      mechanism involved is unknown. In this study, the effects of preincubation with
      AG on oxidant-induced apoptosis, oxidant-induced intracellular reactive oxygen
      species (ROS) production, and lipid peroxidation were determined in rat retinal
      Muller cells and compared with the effects of NGF, a protein that protects
      neuronal cells from oxidative stress. The effect of AG on rabbit vitreous lipid
      peroxide levels was also determined. After exposure to increasing concentrations
      of H2O2, there was a corresponding increase in the percentage of apoptotic Muller
      cells. Preincubation with AG for 48 h completely inhibited oxidant-induced
      apoptosis in response to 10 micromol/l H2O2 (+AG 0 vs. 10 micromol/l, NS), and
      reduced the percentage of apoptotic cells in response to 50 micromol/l H2O2 by
      50% (+AG vs. -AG, P < 0.01). Longer preincubation did not increase the
      antiapoptotic effect of AG. The effect of AG was dose-dependent. Similar results
      were obtained after preincubation with NGF. Both AG and NGF preincubation
      prevented the twofold increase in oxidant-induced lipid peroxides. The fivefold
      increase in oxidant-induced ROS production was decreased 100% by NGF, but only
      61% by AG preincubation. The twofold increase in vitreous lipid peroxide level in
      diabetic rabbits was completely prevented by AG treatment. AG reduced H2O2
      induced benzoate hydroxylation in a dose-dependent manner. Intracellular
      glutathione content was unchanged. These data demonstrate that AG can act as an
      antioxidant in vivo, quenching hydroxyl radicals and lipid peroxidation in cells
      and tissues and preventing oxidant-induced apoptosis.

PMID- 9648837
TI  - Familial and perinatal risk factors for micro- and macroalbuminuria in young IDDM
      patients.
AB  - It has been suggested that hereditary risk for hypertension and cardiovascular
      disease (CVD) as well as intrauterine growth may be involved in the pathogenesis
      of diabetic nephropathy. In the present study, we investigated the influence of
      familial and perinatal risk factors on the occurrence of micro- and
      macroalbuminuria in young IDDM patients. A cohort of 1,150 young patients with >
      or =5 years' duration of IDDM was screened for microalbuminuria. Data on family
      history of hypertension, CVD, IDDM, and NIDDM; perinatal factors such as birth
      weight, gestational age, and duration of breastfeeding; and maternal education,
      smoking, hypertension, and proteinuria during pregnancy were collected. We
      identified 75 patients with an albumin excretion rate > or =15 microg/min in more
      than two overnight urinary samples and compared them in a nested case-control
      study with three normoalbuminuric control subjects per patient from the same
      cohort, matched for diabetes duration. Perinatal factors were analyzed in all
      patients born at term (+/- 2 weeks), 59 of the 75 patients and 155 of the 225
      control subjects. In univariate analysis, hypertension in parents (odds ratio
      [OR] 4.21), CVD in parents and grandparents (OR 1.26), maternal smoking during
      pregnancy (OR 3.21), and a low level of maternal education (OR 2.33) were
      significantly associated with the development of micro- and macroalbuminuria.
      When adjusted for other familial and perinatal factors, current mean blood
      pressure, HbA1c, smoking, BMI, sex, age, and postpubertal diabetes duration,
      using logistic regression analyses, only parental hypertension in all patients
      and maternal smoking during pregnancy and low level of maternal education in full
      term patients were independent risk factors. When patients with poor glycemic
      control were analyzed separately, familial CVD, poor metabolic control, parental
      hypertension, maternal smoking during pregnancy, and level of maternal education
      were independent risk factors, with the adjusted OR markedly increased, compared
      with the matched subgroup with better HbA1c. In conclusion, familial hypertension
      and CVD, maternal smoking during pregnancy, and low level of maternal education
      may independently increase the risk for incipient nephropathy in full-term
      offspring who later develop IDDM. Current poor glycemic control seemed to
      increase the effect of these risk factors.

PMID- 9648838
TI  - Contribution of the endothelium to transcapillary insulin transport in rat
      isolated perfused hearts.
AB  - Capillary endothelial cells are thought to limit the transport of insulin from
      the vascular to the interstitial space, resulting in attenuated hormonal action
      at target sites. This study examined the contribution of endothelial cells to the
      regulation of transcapillary insulin transport in rat hearts in vitro. Hearts
      were perfused with a protein-free buffer that resulted in the generation of a
      substantial amount of interstitial fluid (transudate) that was collected at the
      surface of ventricles. Insulin (0.05-1 U/l) was added to the perfusate, and its
      transfer kinetics to and clearance from the interstitium were analyzed from
      insulin measurements in transudate of hearts with intact or collagenase-disrupted
      endothelium. In endothelium-intact hearts (n = 5-8), the steady-state insulin
      concentration in transudate was 29 +/- 4, 30 +/- 2, 53 +/- 1, 103 +/- 6, and 97
      +/- 4% of perfusate concentrations at 0.05, 0.1, 0.2, 0.5, and 1 U/l insulin,
      respectively. The corresponding apparent rate constants for transport (k(in))
      increased from 0.03/min to -0.27/min, indicating a nonsaturable transport
      process. The transport rate for [3H]insulin (1.2 nmol/l; n = 5) was identical to
      an equimolar concentration of insulin (0.2 U/l), strongly indicating the same
      mode of transport. In endothelium-disrupted hearts (n = 3-5), the same
      perfusate/transudate concentration ratios were observed--that is, a gradient at
      low insulin concentrations (0.05-0.2 U/l) and complete equilibration at higher
      insulin concentrations, suggesting a contribution of reabsorption processes back
      into the vascular space in the generation of the gradient. Finally, inhibition of
      endothelial nitric oxide (NO) formation by NG-nitro-L-arginine (200 micromol/l)
      affected neither k(in) nor the extent of transendothelial insulin transport in
      the presence of an intact endothelium. We concluded that 1) capillary endothelial
      cells affect the transcapillary transport of insulin by slowing the transfer to
      the interstitium, 2) insulin is transported by a bidirectional convective
      transport rather than by a saturable receptor-mediated mechanism, and 3)
      endothelium-derived NO is without effect on transcapillary insulin transport in
      this model.

PMID- 9648839
TI  - Cyclic nucleotide phosphodiesterase 3 expression in vivo: evidence for tissue
      specific expression of phosphodiesterase 3A or 3B mRNA and activity in the aorta
      and adipose tissue of atherosclerosis-prone insulin-resistant rats.
AB  - With a view of understanding the potential roles of phosphodiesterase (PDE)3 in
      the acceleration of atherosclerosis in diabetes, we have analyzed the in vivo
      levels of low Km cAMP PDE3 and PDE4 activities as well as PDE3A and PDE3B mRNA in
      a relevant animal model. The JCR:LA-cp rat is a unique strain that develops
      obesity, insulin resistance, and vasculopathy when homozygous for the autosomal
      recessive cp gene (cp/cp). Lean rats, bred (designated +/?) as a 2:1 mixture of
      animals that are heterozygous (cp/+) or homozygous normal (+/+), are
      metabolically normal. We find that PDE3 activity is the major low Km cAMP
      activity in the aorta of cp/cp rats and is approximately twofold higher than that
      in lean +/? rats. PDE3A mRNA levels in middle-aged cp/cp rats are also elevated,
      approximately threefold, compared with those of +/? rats or young 12-week-old
      cp/cp rats. Thus, in the aorta of atherosclerosis-prone insulin-resistant cp/cp
      rats, PDE3A gene expression is upregulated, resulting in significantly higher
      PDE3 activity. This upregulation of PDE3A mRNA levels was a rather unique
      phenomenon to the aorta of JCR:LA-cp rats compared with that in the aorta of
      other rat strains. This result is consistent with our hypothesis that an
      increased PDE3 activity in aortic smooth muscle cells may contribute to
      accelerated atherosclerosis in diabetes. Furthermore, determination of PDE3
      activity and PDE3A and PDE3B mRNA levels in heart and white and brown fat tissues
      of JCR:LA-cp rats revealed that PDE3B mRNA and activity in white adipose tissue
      is downregulated in this diabetic animal model, and that PDE3A and PDE3B genes
      are tissue-specifically expressed and differentially regulated in aorta and
      adipose tissue, respectively, under hyperinsulinemic conditions.

PMID- 9648840
TI  - Functional analyses of novel mutations in the sulfonylurea receptor 1 associated
      with persistent hyperinsulinemic hypoglycemia of infancy.
AB  - The ATP-sensitive potassium channel, K(ATP) channel, a functional complex of the
      sulfonylurea receptor 1, SUR1, and an inward rectifier potassium channel subunit,
      Kir6.2, regulates insulin secretion in the pancreas. Mutations in both the Kir6.2
      and SUR1 genes are associated with persistent hyperinsulinemic hypoglycemia of
      infancy (PHHI), a disorder of pancreatic beta-cell function characterized by
      excess insulin secretion and hypoglycemia. We have studied the functional
      properties of novel SUR1 mutations identified in PHHI patients, including H125Q,
      N188S, F591L, T1139M, R1215Q, G1382S, and R1394H. R1394H and deltaF1388 SUR1, a
      previously identified PHHI mutation, resulted in no functional channels when
      coexpressed with Kir6.2 in COS cells, while H125Q, N188S, F591L, T1139M, R1215Q,
      and G1382S SUR1 generated functional channels in the absence of ATP. With the
      exception of N188S and H125Q, all mutants had reduced response to stimulation by
      MgADP. These results indicate that lack of, or reduction of, K(ATP) channel
      sensitivity to MgADP is a common molecular defect associated with the disease.
      The mutant channels also showed varied response to activation by the potassium
      channel opener diazoxide. Because these mutations are distributed throughout the
      molecule, our data have new implications for structure-function relationships of
      the K(ATP) channel, suggesting that structural elements in SUR1 outside of the
      two nucleotide-binding folds are also important in regulating channel activity.

PMID- 9648841
TI  - Mutations in hepatocyte nuclear factor 1beta are not a common cause of maturity
      onset diabetes of the young in the U.K.

PMID- 9648842
TI  - Identification of polymorphisms in the receptor for advanced glycation end
      products (RAGE) gene: prevalence in type 2 diabetes and ethnic groups.

PMID- 9648843
TI  - CTLA4 gene haplotypes cannot protect from IDDM in the presence of high-risk HLA
      DQ8 or DQ2 alleles in German families.

PMID- 9648844
TI  - Diabetic patients produce an increase in coronary sinus endothelin 1 after
      coronary artery bypass grafting.
AB  - Diabetes is associated with altered vascular responses, and diabetic patients
      demonstrate increased morbidity and mortality after coronary artery bypass
      grafting (CABG). We tested whether endothelin (ET)-1 levels in this patient
      population differed from those in nondiabetic subjects after CABG. Of 14
      consecutive patients who underwent CABG by the same surgeon, 7 had type 2
      diabetes and 7 were nondiabetic. The two groups did not differ significantly in
      preoperative ejection fraction, number of vessels bypassed, cross-clamp time, or
      Parsonnet's score. Coronary sinus blood samples were obtained before cardioplegic
      arrest and then obtained at 1 and 15 min after each of two reperfusion periods:
      reperfusion A (native coronary perfusion plus the left internal mammary artery),
      reperfusion B (saphenous vein graft perfusion). ET-1 was significantly increased
      at all reperfusion time points in diabetic patients compared with nondiabetic
      patients. In diabetic patients, reperfusion after CABG can trigger the release of
      ET-1, which may be a contributing factor in the increased cardiac morbidity seen
      in this patient population.

PMID- 9648845
TI  - Major susceptibility locus for nephropathy in type 1 diabetes on chromosome 3q:
      results of novel discordant sib-pair analysis.
AB  - Diabetic nephropathy (DN) clusters in families with type 1 diabetes and the
      degree of clustering suggests that a major gene having a common disease allele
      may be responsible. To investigate the chromosomal regions containing genes for
      the renin-angiotensin system, we performed a linkage study using pairs of
      siblings with type 1 diabetes who were discordant for DN. Theoretical
      considerations supported by simulation studies indicated that such discordant
      pairs, rather than the usual concordant pairs, would be more effective in
      detecting a major susceptibility gene for DN. We applied this novel strategy to
      test for linkage between DN and chromosomal regions containing genes for the ACE,
      angiotensinogen (AGT), and angiotensin II type 1 receptor (AT1). Two polymorphic
      markers were genotyped in the vicinity of each of the three loci in 66 discordant
      sib pairs and were analyzed with multipoint methods. The regions containing ACE
      and AGT loci were not linked with DN, while the region containing the AT1 locus
      showed linkage with DN. As a result of these positive findings, eight additional
      polymorphic markers spanning a 63-cM region around AT1 locus were genotyped.
      Linkage was demonstrated between DN and a 20-cM region that includes AT1 (P = 7.7
      x 10(-5)), an obvious candidate gene for DN. To investigate whether AT1 could
      account for the observed linkage, we sequenced all exons, splicing junctions, and
      the promoter region and examined the identified polymorphisms/mutations for
      association with DN using the transmission disequilibrium test. Four new
      polymorphisms in the gene were found, but neither these nor previously described
      polymorphisms were associated with DN. Thus, while our study does not implicate
      AT1 itself in the etiology of DN, it provides very strong evidence that a 20-cM
      region around AT1 contains a major locus for susceptibility to DN.

PMID- 9648846
TI  - Homeobox genes in the developing mouse brain.
AB  - Any list of past and recent findings on vertebrate brain prenatal development
      would have to include the fundamental roles of homeobox genes, the genes encoding
      the nuclear regulatory homeodomain proteins. The discovery of homeobox genes and
      their involvement as master regulatory elements in programming the development of
      an embryo into a complete adult organism has provided a key to our understanding
      of ontogenesis. Also, the correlation of mouse developmental mutants and their
      corresponding human syndromes with mutations in homeobox genes has provided
      further evidence for the fundamental role of homeobox genes during the vertebrate
      brain embryonic development. Here, we review the expression patterns and the
      phenotypes of gene mutations that implicate a large repertoire of mouse homeobox
      genes in the specification of neuronal functions during brain embryogenesis.

PMID- 9648847
TI  - Cloning of zebrafish neurofilament cDNAs for plasticin and gefiltin: increased
      mRNA expression in ganglion cells after optic nerve injury.
AB  - During retinal growth and optic axon regeneration, the differential expression of
      the neuronal intermediate filament proteins, plasticin and gefiltin, in the
      goldfish visual pathway suggests that these proteins support programmed axonal
      growth. To investigate plasticin and gefiltin during axonogenesis, we turned to
      the zebrafish, a system that is more amenable to mutational analysis. As a first
      step, we demonstrated that the intermediate filament compositions of goldfish and
      zebrafish are similar. In addition, the cDNAs for zebrafish plasticin and
      gefiltin were cloned and characterized. Using in situ hybridization in retina, we
      show increased mRNA levels for these proteins following optic nerve crush.
      Zebrafish plasticin and gefiltin peak and return to baseline levels of expression
      more rapidly than in goldfish. Furthermore, in the unoperated eye of experimental
      fish, there was a moderate increase in the levels of plasticin and gefiltin mRNA,
      suggesting that soluble factors influence the expression of these proteins. The
      successive expression of plasticin and gefiltin suggests that these neuronal
      intermediate filament proteins are integral components of axonogenesis. The
      cloning and characterization of cDNAs for plasticin and gefiltin permit
      mutational analyses of these proteins during zebrafish axonogenesis.

PMID- 9648848
TI  - Retrovirus-mediated double transduction of the GTPCH and PTPS genes allows 6
      pyruvoyltetrahydropterin synthase-deficient human fibroblasts to synthesize and
      release tetrahydrobiopterin.
AB  - The tetrahydrobiopterin (BH4) cofactor is essential for the aromatic amino acid
      hydroxylases that are involved in phenylalanine degradation and catecholamine and
      serotonin biosynthesis. Furthermore, BH4 is an essential and limiting cofactor
      for all types of nitric oxide synthases. BH4 deficiency results in
      hyperphenylalaninemia and monoamine neurotransmitter depletion associated with
      progressive mental retardation and is most commonly due to autosomal recessive
      mutations in 6-pyruvoyltetrahydropterin synthase (PTPS), the second enzyme for
      cofactor biosynthesis. Due to the relatively poor blood-brain barrier penetration
      of the cofactor, conventional therapy requires, besides oral doses of synthetic
      BH4, administration of neurotransmitter precursors and an aromatic amino acid
      decarboxylase inhibitor. The outcome of this therapy is not always beneficial. In
      this study we transduced into primary patient fibroblasts the human cDNAs for the
      BH4 biosynthetic enzymes GTP cyclohydrolase I and PTPS, expressed from different
      retroviral vectors. This allowed BH4 biosynthesis in originally PTPS-deficient
      cells. Moreover, the double-transduced fibroblasts released between 200 and 800
      pmol of BH4/10(6) cells/day. Such engineered fibroblasts may be grafted into the
      central nervous system and used as depository cells for constitutive delivery of
      BH4.

PMID- 9648849
TI  - The cell-specific silencer region of the human dopamine beta-hydroxylase gene
      contains several negative regulatory elements.
AB  - Dopamine beta-hydroxylase (DBH) catalyzes the conversion of dopamine to
      noradrenaline and is selectively expressed in noradrenergic and adrenergic
      neurons in the nervous system. Transient transfection assays have indicated that
      cell-specific transcription of the human DBH gene may require a cell-specific
      silencer region residing at -486 to -263 bp upstream of the transcription start
      site. This region includes a putative DBH negative regulatory element (DNRE) with
      sequence homology to the restrictive element-1 (RE1)/neuron-restrictive silencer
      element identified in many other neural-specific genes. However, DNRE exerted
      negative regulation in both neuronal and nonneuronal cells alike, and site
      directed mutation of this element did not significantly diminish the repressive
      activity of the DBH silencer region. Furthermore, expression of RE1-silencing
      transcription factor/neuron-restrictive silencer factor repressed neither DBH nor
      tyrosine hydroxylase promoter activity. We now report identification of three
      protein binding sites in the silencer region of the human DBH gene: SI at -271 to
      -250 bp, SII at -316 to -295 bp, and SIII at -348 to -324 bp. In vitro binding
      studies showed that SI and SIII, but not SII, interact with nuclear proteins from
      DBH-negative cells in a cell-specific manner. Furthermore, SI and SIII
      preferentially repressed the heterologous thymidine kinase and homologous DBH
      proximal promoter activities in nonneuronal cells. Taken together, the cell
      specific silencer function of the upstream DBH region appears to involve several
      cis-regulatory elements, including two cell-specific repressor elements, SI and
      SIII, and a general negative regulatory element, DNRE. Based on these data, we
      propose that a highly restricted pattern of DBH gene expression in
      (nor)adrenergic cells of the nervous system may be controlled by multiple
      negative regulatory elements/silencers.

PMID- 9648850
TI  - Differentiation of a catecholaminergic CNS cell line modifies tyrosine
      hydroxylase transcriptional regulation.
AB  - Recently, a tyrosine hydroxylase (TH)-expressing CNS-derived cell line, CAD, was
      obtained that is capable of undergoing reversible morphological differentiation.
      The isolation of the CAD line allowed us to ask whether different DNA regulatory
      elements direct TH transcription when cells are growing and undifferentiated
      versus postmitotic and differentiated. To this end, we compared expression of a
      transiently transfected bacterial chloramphenicol acetyltransferase reporter gene
      under the transcriptional control of TH 5' flanking DNA in CAD cells grown in the
      presence and absence of serum. Mutational analysis indicates that CAD cells
      differently regulate TH transcription depending on their state of
      differentiation. In both states, the cyclic AMP response element and AP1 site
      each activate transcription. However, in undifferentiated cells, the dyad/E-box
      element represses expression by approximately 2.7-fold, whereas it modestly
      activates transcription in differentiated cells. The role of the dyad/ E-box as a
      repressor correlates well with the two- to threefold lower amount of endogenous
      TH protein present in the undifferentiated CAD cells. This study demonstrates the
      differential use of TH DNA regulatory elements in proliferating, undifferentiated
      and nonproliferating, differentiated immortalized neuronal cells.

PMID- 9648851
TI  - Regional expression and regulation of alternative forms of mRNAs derived from two
      distinct transcription initiation sites of the rat mGluR5 gene.
AB  - Metabotropic glutamate receptor (mGluR) subtype 5 is expressed in both neuronal
      and glial cells and is thought to play an important role in neuronal plasticity.
      This expression is up-regulated during the early postnatal period and is induced
      in cultured astrocytes by specific growth factors. To investigate the mechanism
      underlying the regulation of mGluR5 expression, we isolated and characterized
      genomic clones containing the 5'-upstream exons and their flanking regions of the
      mGluR5 gene. On the basis of the mGluR5 genomic structure, cDNA recloning of the
      5'-extreme region of mGluR5 as well as primer extension analysis indicated that
      mGluR5 mRNA is generated from two alternative first exons, termed exon 1A and
      exon 1B, which are separated by 1,949 bp and then connected to the common exon 2.
      Northern blot and in situ hybridization analyses indicated that two distinct
      transcription initiation sites are commonly used in the expression of mGluR5 mRNA
      in various, but specialized, brain regions and that these two alternative forms
      of mGluR5 mRNA are similarly up-regulated or down-regulated during the early
      postnatal period, depending on the brain regions. The two mRNAs are also
      expressed in cultured astrocytes but respond differently to growth factor
      mediated induction. This study provides the genetic basis indicating the diverse
      mechanisms involved in the regulation of mGluR5 expression.

PMID- 9648852
TI  - Activation of endogenous antioxidant defenses in neuronal cells prevents free
      radical-mediated damage.
AB  - Dopamine (DA) is oxidized to the neurotoxic prooxidant species H2O2, OH., and DA
      quinones. We tested whether dimethyl fumarate (DMF), an electrophile shown to
      induce a pleiotropic antioxidant response in nonneuronal cells, could reduce the
      toxicity of DA metabolites in neural cells. Treatment of the N18-RE-105
      neuroblastoma-retina hybridoma cell line with 30-150 microM dopamine led to cell
      death within 24 h, which increased steeply with dose, decreased with higher
      plating density, and was blocked by the H2O2-metabolizing enzyme catalase.
      Pretreatment with DMF (30 microM, 24 h) significantly attenuated DA and H2O2
      toxicity (40-60%) but not that caused by the calcium ionophore ionomycin. DMF
      treatment also elevated total intracellular GSH and increased activities of the
      antioxidant enzymes quinone reductase (QR), glutathione S-transferase (GST),
      glutathione reductase, and the pentose phosphate enzyme glucose-6-phosphate
      dehydrogenase. To assess the protective efficacy of QR and GST, a stable cell
      line was constructed in which these enzymes were overexpressed. Cell death in the
      overexpressing line was not significantly different from that in a cell line
      expressing normal QR and GST activities, indicating that these two enzymes alone
      are insufficient for protection against DA toxicity. Although the relative
      importance of a single antioxidant enzyme such as QR or GST may be small,
      antioxidant inducers such as DMF may prove valuable as agents that elicit a broad
      spectrum neuroprotective response.

PMID- 9648853
TI  - Cytokine-induced accumulation of very long-chain fatty acids in rat C6 glial
      cells: implication for X-adrenoleukodystrophy.
AB  - X-Adrenoleukodystrophy (X-ALD) is an inherited metabolic disorder of very long
      chain fatty acids (VLCFA) with subsequent manifestation of neuroinflammatory
      disease. To investigate the possible role of proinflammatory cytokines in the X
      ALD disease process, we examined the effect of cytokines on the metabolism of
      VLCFA in C6 glial cells expressing oligodendrocyte-like properties. C6 glial
      cells under serum-free conditions were treated with different combinations of
      cytokines (tumor necrosis factor-alpha, interleukin-1beta, interferon-gamma) or
      cytokine with bacterial lipopolysaccharide (LPS). Cytokine-treated C6 cells had
      higher concentrations of VLCFA, measured as percent weight and also as
      C26:0/C22:0 ratio, which were 300-400% as compared with the controls. We also
      found increased levels of C26:1 in cytokine-treated cells. The accumulation of
      VLCFA paralleled the decrease (35-55%) in peroxisomal beta-oxidation activity and
      a 12- to 14-fold increase in the production of nitric oxide (NO). Individual
      cytokines were unable either to produce NO or to increase the levels of VLCFA in
      C6 cells. Inhibition of cytokine-induced NO production by L-N-methylarginine, an
      inhibitor of NO synthase (NOS), and N-acetylcysteine, an inhibitor of cytokine
      mediated induction of inducible NOS, normalized the peroxisomal beta-oxidation
      activity and the levels of VLCFA, suggesting a role for the proinflammatory
      cytokines and NO toxicity in the neuropathological changes associated with
      abnormal VLCFA metabolism (e.g., X-ALD). X-ALD is a peroxisomal disease having
      deficient oxidation of VLCFA, resulting in the excessive accumulation of VLCFA in
      all tissues but especially in brain. We observed greater increase in levels of
      VLCFA in the inflammatory region of ALD brain (in the demyelinating plaque and
      the area around the plaque) than in the normal-looking area away from the plaque;
      this also indicates that cytokines in the proinflammatory region may augment the
      VLCFA defect caused by the inherited abnormality in X-ALD brain. Although C6
      glial cultured cells do not reflect the X-ALD model precisely, the observed
      relationship between the cytokine-induced inhibition of the oxidation of VLCFA,
      excessive accumulation of VLCFA, and excessive production of NO and their
      normalization by inhibitors of NOS in C6 glial cells suggests that NO-mediated
      toxicity may play a role in VLCFA-associated neuroinflammatory diseases (e.g., X
      ALD).

PMID- 9648854
TI  - Induction of nitric oxide synthase and nitric oxide-mediated apoptosis in
      neuronal PC12 cells after stimulation with tumor necrosis factor
      alpha/lipopolysaccharide.
AB  - Exposure of neuronal PC12 cells, differentiated by nerve growth factor, to tumor
      necrosis factor-alpha (TNF-alpha) and bacterial lipopolysaccharide (LPS) resulted
      in de novo synthesis of inducible nitric oxide synthase (iNOS) mRNA and protein
      with an increase up to 24 h. Brain NOS expression was unaffected. The induction
      of iNOS in differentiated PC12 cells was associated with cell death characterized
      by features of apoptosis. The NOS inhibitors N-monomethylarginine,
      aminoguanidine, and 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine.HCl prevented
      TNF-alpha/LPS-induced cell death and DNA fragmentation, suggesting that the TNF
      alpha/LPS-induced cell death is mediated by iNOS-derived NO. This hypothesis is
      supported by the finding that addition of L-arginine, which serves as a precursor
      and limiting factor of enzyme-derived NO production, potentiated TNF-alpha/LPS
      induced loss of viability.

PMID- 9648855
TI  - Oxidative stress induces a form of programmed cell death with characteristics of
      both apoptosis and necrosis in neuronal cells.
AB  - Oxidative stress is implicated in a number of neurological disorders including
      stroke, Parkinson's disease, and Alzheimer's disease. To study the effects of
      oxidative stress on neuronal cells, we have used an immortalized mouse
      hippocampal cell line (HT-22) that is particularly sensitive to glutamate. In
      these cells, glutamate competes for cystine uptake, leading to a reduction in
      glutathione and, ultimately, cell death. As it has been reported that protein
      kinase C activation inhibits glutamate toxicity in these cells and is also
      associated with the inhibition of apoptosis in other cell types, we asked if
      glutamate toxicity was via apoptosis. Morphologically, glutamate-treated cells
      underwent plasma membrane blebbing and cell shrinkage, but no DNA fragmentation
      was observed. At the ultrastructural level, there was damage to mitochondria and
      other organelles although the nuclei remained intact. Protein and RNA synthesis
      inhibitors as well as certain protease inhibitors protected the cells from
      glutamate toxicity. Both the macromolecular synthesis inhibitors and the protease
      inhibitors had to be added relatively soon after the addition of glutamate,
      suggesting that protein synthesis and protease activation are early and distinct
      steps in the cell death pathway. Thus, the oxidative stress brought about by
      treatment with glutamate initiates a series of events that lead to a form of cell
      death distinct from either necrosis or apoptosis.

PMID- 9648856
TI  - Association of the Src family tyrosine kinase Fyn with TrkB.
AB  - Fyn tyrosine kinase, a member of the Src family, was recently reported to be
      present in neurons and glia cells. We investigated whether Fyn is involved in the
      Trk-dependent signal transduction pathways of neurotrophin. The Fyn-Src homology
      domain 2 (SH2) was observed to associate in vitro with the intracellular domain
      of TrkB (ICD-TrkB). This association was dependent on the autophosphorylation of
      ICD-TrkB. The Fyn-SH2 domains bound to phosphorylated ICD-TrkB (pICD-TrkB) with
      an affinity similar to the binding of phospholipase Cgamma (PLCgamma)-SH2 domains
      to its autophosphorylation site in TrkB. The Src-SH2 domains showed substantially
      lower affinity with pICD-TrkB, suggesting that the association between Fyn-SH2
      and pICD-TrkB is not due to nonspecific interactions of SH2 domains with
      phosphorylated tyrosine residues. This is further supported by the observation
      that Fyn-SH2 was able to trap phosphorylated TrkB in cell lysate prepared from
      primary rat cortical neurons stimulated with brain-derived neurotrophic factor
      (BDNF). In contrast, endogenous Fyn was coprecipitated with TrkB from cortical
      neurons without BDNF stimulation. This basal association showed a threefold
      increase on BDNF stimulation, probably due to the SH2/phosphotyrosine interaction
      that was observed in the cell-free system. All these data suggest the involvement
      of Fyn in the neurotrophin signal transduction pathways downstream of TrkB.

PMID- 9648857
TI  - AMPA receptor-mediated excitotoxicity in human NT2-N neurons results from loss of
      intracellular Ca2+ homeostasis following marked elevation of intracellular Na+.
AB  - Human NT2-N neurons express Ca2+-permeable alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionic acid glutamate receptors (AMPA-GluRs) and become
      vulnerable to excitotoxicity when AMPA-GluR desensitization is blocked with
      cyclothiazide. Although the initial increase in intracellular Ca2+ levels
      ([Ca2+]i) was 1.9-fold greater in the presence than in the absence of
      cyclothiazide, Ca2+ entry via AMPA-GluRs in an early phase of the exposure was
      not necessary to elicit excitotoxicity in these neurons. Rather, subsequent
      necrosis was caused by a >40-fold rise in [Na+]i, which induced a delayed [Ca2+]i
      rise. Transfer of the neurons to a 5 mM Na+ medium after AMPA-GluR activation
      accelerated the delayed [Ca2+]i rise and intensified excitotoxicity. Low-Na+
      medium-enhanced excitotoxicity was partially blocked by amiloride or dizocilpine
      (MK-801), and completely blocked by removal of extracellular Ca2+, suggesting
      that Ca2+ entry by reverse operation of Na+/Ca2+ exchangers and via NMDA
      glutamate receptors was responsible for the neuronal death after excessive Na+
      loading. Our results serve to emphasize the central role of neuronal Na+ loading
      in AMPA-GluR-mediated excitotoxicity in human neurons.

PMID- 9648858
TI  - Increase of adenylate kinase isozyme 1 protein during neuronal differentiation in
      mouse embryonal carcinoma P19 cells and in rat brain primary cultured cells.
AB  - Adenylate kinase (AK), which catalyzes the equilibrium reaction among AMP, ADP,
      and ATP, is considered to participate in the homeostasis of energy metabolism in
      cells. Among three vertebrate isozymes, AK isozyme 1 (AK1) is present prominently
      in the cytosol of skeletal muscle and brain. When mouse embryonal carcinoma P19
      cells were differentiated by retinoic acid into neural cells, the amount of AK1
      protein and enzyme activity increased about fivefold concomitantly with
      neurofilament (NF). Double-immunofluorescence staining showed that both AK1 and
      NF were located in neuronal processes as well as the perinuclear regions in
      neuron-like cells, but not in glia-like cells. The amount of brain-type creatine
      kinase increased only twofold during P19 differentiation. The AK isozyme 2, which
      was not detected in adult mouse brain, was found in P19 cells and did not
      increase during the differentiation. Mitochondrial AK isozyme 3, which uses GTP
      instead of ATP as a phosphate donor, was increased significantly.
      Immunohistochemical analysis with the primary cultured cells from rat cerebral
      cortex showed similar cellular localization of AK1 to those observed with
      differentiated P19 cells. These results suggest an important role of this enzyme
      in neuronal functions and in neuronal differentiation.

PMID- 9648859
TI  - Nuclear factor of activated T cells (NFAT) as a new component of the signal
      transduction pathway in glioma cells.
AB  - Cyclosporin A (CsA) exerts its immunosuppressive effect by inhibiting the
      activity of nuclear factor of activated T cells (NFAT), thus preventing
      transcriptional induction of several cytokine genes. This effect is mediated
      through inactivation of the phosphatase calcineurin, which inhibits translocation
      of an NFAT component to the nucleus. We have previously reported that CsA
      inhibits the growth of rat C6 glioma cells in a dose-dependent manner and induces
      apoptotic cell death. Here, we report that NFAT DNA-binding activity is present
      in the nuclear extracts from C6 glioma cells and that CsA treatment inhibits the
      formation of a functional NFAT complex. We provide evidence for the presence of a
      group of NFATc proteins in proliferating glioma cells. Immunoblot analyses show
      that stimulation of C6 glioma cells with a calcium-inducing agent, ionomycin,
      alters NFATc migration on sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. This alteration is inhibited by simultaneous treatment with CsA,
      suggesting a calcineurin involvement in the regulation of glioma NFATc proteins.
      Direct immunofluorescence reveals the presence of NFATc proteins in nuclei of
      proliferating glioma cells and their disappearance in CsA-treated cells. These
      data point to a new mechanism of transcription regulation in glioma cells and
      provide an explanation for the observed sensitivity of glioma cells to CsA.

PMID- 9648860
TI  - Functional analysis and tissue-specific expression of Drosophila Na+,K+-ATPase
      subunits.
AB  - We have previously purified and characterized a nervous system-specific
      glycoprotein antigen from adult Drosophila heads, designated Nervana [nerve
      antigen (NRV)] and identified two separate genes coding for three different
      proteins. All three proteins share homology with the beta subunits of Na+,K+
      ATPase from various other species. In this study we have isolated a new
      Drosophila Na+,K+-ATPase alpha subunit cDNA clone (PSalpha; GenBank accession no.
      AF044974) and demonstrate expression of functional Na+,K+-ATPase activity when
      PSalpha mRNA is coinjected into Xenopus oocytes along with any of the three
      different Nrv mRNAs. Western blotting, RNase protection assays, and
      immunocytochemical staining of adult fly sections indicate that NRV2 is expressed
      primarily in the nervous system. Staining is most intense in the brain and
      thoracic ganglia and is most likely associated with neuronal elements. NRV1 is
      more broadly expressed in muscle and excretory tissue and also shows diffuse
      distribution in the nervous system. Similar to other species, Drosophila
      expresses multiple isoforms of Na+,K+-ATPase subunits in a tissue- and cell type
      specific pattern. It will now be possible to use the advantages of Drosophila
      molecular and classical genetics to investigate the phenotypic consequences of
      altering Na+,K+-ATPase expression in various cell and tissue types.

PMID- 9648861
TI  - The calcitonin gene-related peptide-induced acetylcholinesterase synthesis in
      cultured chick myotubes is mediated by cyclic AMP.
AB  - In vertebrate neuromuscular junctions, post-synaptic specialization includes
      aggregation of acetylcholine receptors (AChRs) and acetylcholinesterase (AChE).
      The motor nerve provides soluble factors and electrical activity to achieve this
      striking localization of AChRs/AChE. Calcitonin gene-related peptide (CGRP), a
      neuropeptide synthesized by motor neurons, is able to stimulate the expression of
      AChR in cultured myotubes. Similar to AChR regulation, synthesis of AChE in
      cultured chick myotubes is also stimulated by CGRP. Application of CGRP onto
      cultured myotubes stimulated the accumulation of intracellular cyclic AMP (cAMP)
      as well as the expression of AChE mRNA and protein. However, the enzymatic
      activity of AChE remained unchanged. In cultured myotubes, various drugs
      affecting the intracellular level of cAMP, such as N6,O2'-dibutyryladenosine
      3',5'-cyclic monophosphate, cholera toxin, and forskolin, could mimic the effect
      of CGRP in stimulating the expression of AChE. When myotubes were transfected
      with cDNA encoding constitutively active mutant Galpha(s), the intracellular cAMP
      synthesis was increased. The increase in cAMP level was in parallel with an
      increase in the expression of AChE, whereas transfection of active mutant
      Galpha(i) cDNA decreased the cAMP level as well as the AChE expression. In
      addition, expression of collagen-tailed AChE was up-regulated by the cAMP
      pathway. These findings indicated that CGRP-induced AChE regulation is mediated
      by the cAMP pathway and represented the first evidence to suggest that the
      regulation of mRNA synthesis of AChR and AChE can be mediated by the same neuron
      derived factor.

PMID- 9648862
TI  - Neurotrophic factors prevent ceramide-induced apoptosis downstream of c-Jun N
      terminal kinase activation in PC12 cells.
AB  - Neurotrophic factors prevent apoptosis of PC12 cells in serum-free medium. The
      present study determines whether neurotrophic factors can prevent ceramide
      induced apoptosis in PC12 cells and investigates the role that c-Jun N-terminal
      kinase (JNK) activation may play in this system. Ceramide-induced apoptosis was
      inhibited by nerve growth factor, basic fibroblast growth factor, pituitary
      adenylyl cyclase-activating peptide, 4-(8-chlorophenylthio)cyclic AMP, and the
      caspase inhibitor benzyloxycarbonyl-Val-Ala-DL-Asp fluoromethyl ketone (zVAD
      FMK). It was surprising that inhibition of extracellular signal-regulated kinase
      and/or phosphatidylinositol 3-kinase did not markedly block the protective
      effects exerted by neurotrophic factors against ceramide-induced apoptosis,
      suggesting that neurotrophic factors can promote survival independently of these
      signaling pathways. Treatment of PC12 cells with ceramide resulted in a time
      dependent increase in JNK activity. However, neither neurotrophic factors nor
      zVAD-FMK attenuated ceramide-stimulated JNK activation. Further experiments
      indicated that ceramide-induced apoptosis in PC12 cells requires new protein
      synthesis, and that nerve growth factor and zVAD-FMK can prevent apoptosis after
      JNK activity has been detected. These results indicate that ceramide-induced JNK
      activation is an early event and may be required for the expression of essential
      components of the apoptotic machinery. It is anticipated that neurotrophic
      factors inhibit ceramide-induced apoptosis by affecting signaling events
      downstream of JNK activation.

PMID- 9648863
TI  - Age-dependent differential regulation of sensory neuropeptides by glial cell line
      derived neurotrophic factor.
AB  - Glial cell line-derived neurotrophic factor markedly enhances survival of
      neonatal dorsal root sensory neurons in vitro, an effect seen even in the
      presence of anti-nerve growth factor. Furthermore, it increases levels of
      substance P, inducing more than a sixfold rise that is maximal at 10 ng/ml. At
      the same dose, it potentiates the action of nerve growth factor on substance P
      but not on survival. Neither factor increases somatostatin content in neonatal
      neurons. Although its effect on substance P diminishes with age, glial cell line
      derived neurotrophic factor dramatically increases somatostatin levels in neurons
      from adult rats. Glial cell line-derived neurotrophic factor is therefore the
      second trophic factor found to promote survival and regulate substance P in
      neonatal sensory neurons. More significant is that it is the first and sole
      neurotrophic factor reported to regulate somatostatin in sensory neurons at any
      age, with its effect restricted to the adult. These results suggest mechanisms
      for differential regulation of somatostatin versus substance P in nociceptive
      pathways.

PMID- 9648864
TI  - Src homology domains of phospholipase C gamma1 inhibit nerve growth factor
      induced differentiation of PC12 cells.
AB  - Phospholipase C gamma1 (PLC-gamma1) is phosphorylated on treatment of cells with
      nerve growth factor (NGF). To assess the role of PLC-gamma1 in mediating the
      neuronal differentiation induced by NGF treatment, we established PC12 cells that
      overexpress whole PLC-gamma (PLC-gamma1PC12), the SH2-SH2-SH3 domain (PLC
      gamma1SH223PC12), SH2-SH2-deleted mutants (PLC-gamma1deltaSH22PC12), and SH3
      deleted mutants (PLC-gamma1deltaSH3PC12). Overexpressed whole PLC-gamma1 or the
      SH2-SH2-SH3 domain of PLC-gamma1 stimulated cell growth and inhibited NGF-induced
      neurite outgrowth of PC12 cells. However, cells expressing PLC-gamma1 lacking the
      SH2-SH2 domain or the SH3 domain had no effect on NGF-induced neuronal
      differentiation. Overexpression of intact PLC-gamma1 resulted in a threefold
      increase in total inositol phosphate accumulation on treatment with NGF. However,
      overexpression of the SH2-SH2-SH3 domain of PLC-gamma1 did not alter total
      inositol phosphate accumulation. To investigate whether the SH2-SH2-SH3 domain of
      PLC-gamma1 can mediate the NGF-induced signal, tyrosine phosphorylation of the
      SH2-SH2-SH3 domain of PLC-gamma1 on NGF treatment was examined. The SH2-SH2-SH3
      domain of PLC-gamma1 as well as intact PLC-gamma1 could be tyrosine
      phosphorylated on NGF treatment. These results indicate that the overexpressed
      SH2-SH2-SH3 domain of PLC-gamma1 can block the differentiation of PC12 cells
      induced by NGF and that the inhibition appears not to be related to the lipase
      activity of PLC-gamma1 but to the SH2-SH2-SH3 domain of PLC-gamma1.

PMID- 9648865
TI  - Evidence for activation of caspase-3-like protease in excitotoxin- and
      hypoxia/hypoglycemia-injured neurons.
AB  - Caspase activation has been shown to be a critical step in several models of
      neuronal apoptosis such as staurosporine treatment of human neuroblastoma SH-SY5Y
      cells and potassium deprivation of rat cerebellar granule neurons. One common
      event is the appearance of caspase-mediated 120-kDa nonerythroid alpha-spectrin
      breakdown product (SBDP120). Second, inhibitors of the caspase family are
      effective blockers of such neuronal death. In this study, we report the
      appearance of caspase-mediated SBDP120 in excitotoxin-challenged fetal rat
      cerebrocortical neurons [N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid, and kainate] and rat cerebellar granule neurons
      (NMDA and kainate). A general caspase inhibitor, carbobenzoxy-Asp-CH2OC(O)-2,6
      dichlorobenzene (Z-D-DCB), blocked the formation of SBDP120 under these
      conditions and attenuated the observed NMDA-induced lactate dehydrogenase (LDH)
      release in both cell types. Furthermore, hydrolytic activity toward a caspase-3
      preferred synthetic peptide substrate, acetyl-DEVD-7-amido-4-methylcoumarin, was
      significantly elevated in NMDA-treated granule neurons. Lastly, oxygen-glucose
      deprivation (OGD)-challenged cerebrocortical cultures also showed the appearance
      of SBDP120. Again, Z-D-DCB blocked the SBDP120 formation as well as attenuated
      the LDH release from the OGD-challenged neurons. Taken together, the presence of
      caspase-specific SBDP120 and the neuroprotective effects of Z-D-DCB strongly
      suggest that caspase activation contributes at least in part to excitotoxin- and
      OGD-induced neuronal death.

PMID- 9648866
TI  - Ethanol induces apoptosis in cerebellar granule neurons by inhibiting insulin
      like growth factor 1 signaling.
AB  - The ability of ethanol to interfere with insulin-like growth factor 1 (IGF-1)
      mediated cell survival was examined in primary cultured cerebellar granule
      neurons. Cells underwent apoptosis when switched from medium containing 25 mM K+
      to one containing 5 mM K+. IGF-1 protected granule neurons from apoptosis in
      medium containing 5 mM K+. Ethanol inhibited IGF-1-mediated neuronal survival but
      did not inhibit IGF-1 receptor binding or the neurotrophic action of elevated K+,
      and failed to potentiate cell death in the presence of 5 mM K+. Inhibition of
      neuronal survival by ethanol was not reversed by increasing the concentration of
      IGF-1. Significant inhibition by ethanol (15-20%) was observed at 1 mM and was
      half-maximal at 45 mM. The inhibition of IGF-1 protection by ethanol corresponded
      to a marked reduction in the phosphorylation of insulin receptor substrate 1, the
      binding of phosphatidylinositol 3-kinase (PI 3-kinase), and a block of IGF-1
      stimulated PI 3-kinase activity. The neurotrophic response of IGF-1 was also
      inhibited by the PI 3-kinase inhibitor LY294002, the protein kinase C inhibitor
      chelerythrine chloride, and the protein kinase A inhibitor KT5720, but unaffected
      by the mitogen-activated protein kinase kinase inhibitor PD 98059. These data
      demonstrate that ethanol promotes cell death in cerebellar granule neurons by
      inhibiting the antiapoptotic action of IGF-1.

PMID- 9648867
TI  - Endothelin-stimulated capacitative calcium entry in enteric glial cells:
      synergistic effects of protein kinase C activity and nitric oxide.
AB  - Depletion of intracellular calcium stores by agonist stimulation is coupled to
      calcium influx across the plasma membrane, a process termed capacitative calcium
      entry. Capacitative calcium entry was examined in cultured guinea pig enteric
      glial cells exposed to endothelin 3. Endothelin 3 (10 nM) caused mobilization of
      intracellular calcium stores followed by influx of extracellular calcium. This
      capacitative calcium influx was inhibited by Ni2+ (89 +/- 2%) and by La3+ (78 +/-
      2%) but was not affected by L-, N-, or P-type calcium channel blockers.
      Chelerythrine, a specific antagonist of protein kinase C, dose-dependently
      inhibited capacitative calcium entry. The nitric oxide synthase inhibitor NG
      nitro-L-arginine decreased calcium influx in a dose-dependent manner. The
      combination of chelerythrine and NG-nitro-L-arginine produced synergistic
      inhibitory effects. Capacitative calcium entry occurs in enteric glial cells via
      lanthanum-inhibitable channels through a process regulated by protein kinase C
      and nitric oxide.

PMID- 9648868
TI  - Inhibition of phosphorylation of TrkB and TrkC and their signal transduction by
      alpha2-macroglobulin.
AB  - Monoamine-activated alpha2-macroglobulin (alpha2M) was shown to reduce the
      dopamine concentration in corpus striatum of adult rat brains and inhibit other
      neuronal functions in vivo and in vitro. As brain-derived neurotrophic factor,
      neurotrophin-4, and neurotrophin-3 are important neurotrophic factors for
      dopaminergic neurons, the effect of monoamine-activated alpha2M on signal
      transduction by trkB and trkC was investigated. The results show that monoamine
      activated alpha2M binds to trkB and inhibits brain-derived neurotrophic
      factor/neurotrophin-4-promoted autophosphorylation of trkB in a dose-dependent
      manner in both trkB-expressing NIH3T3 (NIH3T3-trkB) and human neuroblastoma SH
      SY5Y cells. Monoamine-activated alpha2M also blocks tyrosine phosphorylation of
      phospholipase C-gamma1 and extracellular signal-regulated protein kinase (ERK)-1,
      which are key intracellular proteins involved in trkB signal transduction.
      Similarly, monoamine-activated alpha2M inhibits tyrosine phosphorylation of
      neurotrophin-3-induced trkC and its signal transduction in a dose-dependent
      manner in NIH3T3 cells expressing trkC (NIH3T3-trkC). In contrast to monoamine
      activated alpha2M, normal alpha2M has little or no significant inhibitory effect
      on the phosphorylation of trkB and trkC. In addition, the retinoic acid-promoted
      tyrosine phosphorylation of phospholipase C-gamma1, ERK-1, and/or ERK-2 in SH
      SY5Y cells was unaffected by monoamine-activated alpha2M; this suggests that the
      inhibitory effect of activated alpha2M on the neurotrophin-stimulated
      phosphorylation of intracellular signalling proteins may be specific. Taken
      together, the data indicate that activated alpha2M is a pan-trk inhibitor, which
      by virtue of its binding to trk receptors may block trk-mediated signal
      transduction in dopaminergic neurons and lead to reduction of dopamine
      concentration in corpus striatum.

PMID- 9648869
TI  - Cyclopentyladenosine-induced homologous down-regulation of A1 adenosine receptors
      (A1AR) in intact neurons is accompanied by receptor sequestration but not a
      reduction in A1AR mRNA expression or G protein alpha-subunit content.
AB  - We showed previously that exposure of cerebellar granule cells to the A1
      adenosine receptor (A1AR)-selective agonist, cyclopentyladenosine, decreases A1AR
      density and G protein coupling corresponding to blunted agonist-induced adenylyl
      cyclase (EC 4.6.1.1) inhibition. We have now determined that A1AR-mediated
      adenylyl cyclase inhibition was desensitized in a homologous manner. Carbachol-
      and baclofen-induced inhibition of adenylyl cyclase was unaffected by 48-h
      exposure to 10 microM cyclopentyladenosine. Expression of G protein alpha
      subunits was not affected dramatically by agonist exposure. The fraction of
      sequestered A1AR was increased significantly at 4, 24, and 48 h of
      cyclopentyladenosine exposure (35, 57, and 81% increase over control,
      respectively). The time course of agonist-induced A1AR sequestration was slower
      than that reported for other G protein-coupled receptors. Incubation with the
      adenosine receptor antagonist, 8-p-sulfophenyltheophylline or adenosine deaminase
      did not alter sequestration significantly. Neither steady-state A1AR mRNA levels
      nor transcript stability was affected by 48-h agonist exposure. We determined
      that A1AR half-life in cerebellar granule cells is 20.9 h, which is considerably
      longer than that reported for several other G protein-coupled receptors. The slow
      time course of A1AR sequestration and the stability of the corresponding mRNA may
      be a reflection of the tonic inhibitory tone exerted by adenosine in brain.

PMID- 9648870
TI  - Distinct differences between morphine- and [D-Ala2,N-MePhe4,Gly-ol5]-enkephalin
      mu-opioid receptor complexes demonstrated by cyclic AMP-dependent protein kinase
      phosphorylation.
AB  - The present study demonstrates a conditional, agonist-dependent phosphorylation
      of the mu-opioid receptor (MOR-1) by cyclic AMP-dependent protein kinase (PKA) in
      membrane preparations of MOR-1-transfected neuroblastoma Neuro2A cells. Opioid
      agonist-dependent phosphorylation occurs in a time- and concentration-dependent
      manner (EC50 approximately 40 nM) and can be abolished by the receptor antagonist
      naloxone. Stoichiometric analysis indicates incorporation of a maximum of 6 mol
      of phosphate/mol of receptor in the presence of 1 microM morphine and 6 nM PKA.
      Although morphine and related alkaloids as well as some peptide agonists (PLO17
      and beta-endorphin) stimulated phosphorylation of MOR-1 by PKA, the potent mu
      opioid-selective peptide [D-Ala2,N-MePhe4,Gly-ol5]-enkephalin (DAMGO) or other
      enkephalin analogues such as [D-Ala2]-Met5-enkephalinamide (DALA), [D-Ala2,D
      Leu5]-enkephalin (DADLE), and Met5-enkephalin had no effect. The lack of the
      effect of DAMGO on MOR-1 phosphorylation state was evident also after chronic
      pretreatment. These results suggest the existence of different agonist-dependent
      conformations of MOR-1. Furthermore, phosphorylation may be a useful parameter
      with which to identify different agonist-receptor conformations.

PMID- 9648871
TI  - Tissue transglutaminase is an in situ substrate of calpain: regulation of
      activity.
AB  - Tissue transglutaminase (tTG) is a calcium-dependent enzyme that catalyzes the
      transamidation of specific polypeptide-bound glutamine residues, a reaction that
      is inhibited by GTP. There is also preliminary evidence that, in situ, calpain
      and GTP may regulate tTG indirectly by modulating its turnover by the calcium
      activated protease calpain. In the present study, the in vitro and in situ
      proteolysis of tTG by calpain, and modulation of this process by GTP, was
      examined. tTG is an excellent substrate for calpain and is rapidly degraded.
      Previously it has been demonstrated that GTP binding protects tTG from
      degradation by trypsin. In a similar manner, guanosine-5'-O-(3-thiotriphosphate)
      protects tTG against proteolysis by calpain. Treatment of SH-SY5Y cells with 1 nM
      maitotoxin, which increases intracellular calcium levels, resulted in a
      significant increase in in situ TG activity, with only a slight decrease in tTG
      protein levels. In contrast, when GTP levels were depleted by pretreating the
      cells with tiazofurin, maitotoxin treatment resulted in an approximately 50%
      decrease in tTG protein levels, and a significant decrease in TG activity,
      compared with maitotoxin treatment alone. Addition of calpain inhibitors
      inhibited the degradation of tTG in response to the combined treatment of
      maitotoxin and tiazofurin and resulted in a significant increase in in situ TG
      activity. These studies indicate that tTG is an endogenous substrate of calpain
      and that GTP selectively inhibits the degradation of tTG by calpain.

PMID- 9648872
TI  - Pertussis toxin modification of PC12 cells inhibits a protein phosphatase 2A-like
      phosphatase.
AB  - We have found that modification of rat PC12 cells with pertussis toxin resulted
      in an approximately 50% inhibition of a protein phosphatase 2A-like phosphatase.
      Protein phosphatase 2A (PP2A) is a major cellular serine/threonine-specific
      protein phosphatase. Treatment of extracts from pertussis toxin-modified PC12
      cells with either immobilized alkaline phosphatase or Ca2+ reversed this
      inhibition. Reactivation of the PP2A-like phosphatase in Ca2+ appears to result
      from the dephosphorylation of a protein by the Ca2+/calmodulin-dependent protein
      phosphatase calcineurin. The PP2A-like phosphatase in extracts from pertussis
      toxin-modified PC12 cells eluted from a Mono Q column at a higher ionic strength
      than did the PP2A-like phosphatase in extracts from control cells. After
      incubation in Ca2+, the PP2A-like phosphatase in extracts from pertussis toxin
      modified cells eluted from a Mono Q column at the same ionic strength as did the
      PP2A-like phosphatase in extracts from control cells. These results indicate that
      the effect of pertussis toxin on this PP2A-like activity results from the
      phosphorylation of either one of the subunits of the PP2A-like phosphatase or a
      protein that when phosphorylated binds to and inhibits this phosphatase.
      Pertussis toxin modification did not result in the phosphorylation of the
      catalytic subunit of PP2A. Because phosphorylation regulates the activities of
      many enzymes and cell surface receptors, a pertussis toxin-induced decrease in
      PP2A activity could alter signaling pathways and other cellular processes in
      which G proteins are not directly involved.

PMID- 9648873
TI  - Lobeline displaces [3H]dihydrotetrabenazine binding and releases [3H]dopamine
      from rat striatal synaptic vesicles: comparison with d-amphetamine.
AB  - Lobeline, an alkaloid from Indian tobacco (Lobelia inflata), is classified as a
      nicotinic agonist and is currently used as a smoking cessation agent. However,
      our previous in vitro studies demonstrate that lobeline does not act as a
      nicotinic agonist but alters presynaptic dopamine (DA) storage by potently
      inhibiting DA uptake into synaptic vesicles. Recently, d-amphetamine has been
      reported to act at the level of the synaptic vesicle to alter presynaptic
      function. The present in vitro studies further elucidate the mechanism of
      lobeline's action and compare its effects with those of d-amphetamine.
      [3H]Dihydrotetrabenazine ([3H]DTBZ), used routinely to probe a high-affinity
      binding site on the vesicular monoamine transporter (VMAT2), bound to vesicle
      membranes from rat striatum with a KD of 1.67 nM and Bmax of 8.68 pmol/mg of
      protein. Lobeline inhibited [3H]DTBZ binding with an IC50 of 0.90 microM,
      consistent with its previously reported IC50 of 0.88 microM for inhibition of
      [3H]DA uptake into vesicles. These results suggest that lobeline specifically
      interacts with DTBZ sites on VMAT2 to inhibit DA uptake into synaptic vesicles.
      Interestingly, d-amphetamine inhibited [3H]DTBZ binding to vesicle membranes with
      an IC50 of 39.4 microM, a concentration 20 times greater than reported for
      inhibition of VMAT2 function, suggesting that d-amphetamine interacts with a
      different site than lobeline on VMAT2 to inhibit monoamine uptake. Kinetic
      analysis of [3H]DA release from [3H]DA-preloaded synaptic vesicles in the absence
      of drug revealed a t1/2 of 2.12 min. Lobeline and d-amphetamine evoked [3H]DA
      release with EC50 values of 25.3 and 2.22 microM, respectively. At a
      concentration 10 times the EC50, lobeline and d-amphetamine significantly
      decreased the t1/2 of [3H]DA release to 1.58 and 1.48 min, respectively. Thus, in
      contrast to d-amphetamine, which is equipotent in inhibiting DA uptake and
      promoting release from the synaptic vesicles, lobeline more potently (28-fold)
      inhibits DA uptake (via an interaction with the DTBZ site on VMAT2) than it
      evokes DA release to redistribute presynaptic DA storage.

PMID- 9648874
TI  - Nitric oxide-induced release of acetylcholine in the nucleus accumbens: role of
      cyclic GMP, glutamate, and GABA.
AB  - We have previously shown that the basal acetylcholine release in the ventral
      striatum is under the enhancing influence of endogenous nitric oxide (NO) and
      that NO donors cause pronounced increases in the acetylcholine release rate. To
      investigate the role of cyclic GMP, glutamate, and GABA in the NO-induced
      acetylcholine release, we superfused the nucleus accumbens, (Nac) of the
      anesthetized rat with various compounds through a push-pull cannula and
      determined the neurotransmitter released in the perfusate. Superfusion of the Nac
      with the NO donors diethylamine/NO (DEANO; 100 micromol/L), S-nitroso-N
      acetylpenicillamine (SNAP; 200 micromol/L), or 3-morpholinosydnonimine (SIN-1;
      200 micromol/L) enhanced the acetylcholine release rate. The guanylyl cyclase
      inhibitor 1H-(1,2,4)-oxodiazolo(4,3-a)quinoxalin-1-one (ODQ; 10 micromol/L)
      abolished the effects of DEANO and SIN-1. 6-(Phenylamino)-5,8-quinolinedione (LY
      83583; 100 micromol/L), which also inhibits cyclic GMP synthesis, inhibited the
      releasing effects of DEANO and of SNAP, whereas the effect of SIN-1 on
      acetylcholine release was not influenced. The DEANO-induced release of
      acetylcholine was also abolished in the presence of 20 micromol/L 6,6
      dinitroquinoxaline-2,3-dione (DNQX) and 10 micromol/L (+/-)-2-amino-5
      phosphonopentanoic acid (AP-5). Simultaneous superfusion with 50 micromol/L
      quinpirole and 10 micromol/L 7-bromo-8-hydroxy-3-methyl-1-phenyl-2,3,4,5
      tetrahydro-1H-3-benzazepine (SKF 83566) was ineffective. Superfusion with 500
      micromol/L DEANO decreased the release of acetylcholine. The inhibitory effect of
      500 micromol/L DEANO was reversed to an enhanced release on superfusion with 20
      micromol/L bicuculline. Bicuculline also enhanced the basal release rate. These
      findings indicate that cyclic GMP mediates the NO-induced release of
      acetylcholine by enhancing the outflow of glutamate. Dopamine is not involved in
      this process. Only high concentrations of NO increase the output of GABA, which
      in turn decreases acetylcholine release. Our results suggest that cells that are
      able to release glutamate, such as glutamatergic neurons, are the main target of
      NO in the Nac.

PMID- 9648875
TI  - Regulation of extracellular dopamine by the norepinephrine transporter.
AB  - There is growing evidence of an interaction between dopamine and norepinephrine.
      To test the hypothesis that norepinephrine terminals are involved in the uptake
      and removal of dopamine from the extracellular space, the norepinephrine uptake
      blocker desmethylimipramine (DMI) was infused locally while the extracellular
      concentrations of dopamine were simultaneously monitored. DMI increased the
      extracellular concentrations of dopamine in the medial prefrontal cortex and
      nucleus accumbens shell but had no effect in the striatum. The combined systemic
      administration of haloperidol and the local infusion of DMI produced an augmented
      increase in extracellular dopamine in the cortex compared with the increase
      produced by either drug alone. This synergistic increase in dopamine overflow is
      likely due to the combination of impulse-mediated dopamine release produced by
      haloperidol and blockade of the norepinephrine transporter. No such synergistic
      effects were observed in the nucleus accumbens and striatum. Local perfusion of
      the alpha2-antagonist idazoxan also increased the extracellular concentrations of
      dopamine in the cortex. Although the stimulation of extracellular dopamine by
      idazoxan and DMI could be due to the increased extracellular concentrations of
      norepinephrine produced by these drugs, an increase in dopamine also was observed
      in lesioned rats that were depleted of norepinephrine and challenged with
      haloperidol. This contrasted with the lack of an effect of haloperidol on
      cortical dopamine in unlesioned controls. These results suggest that
      norepinephrine terminals regulate extracellular dopamine concentrations in the
      medial prefrontal cortex and to a lesser extent in the nucleus accumbens shell
      through the uptake of dopamine by the norepinephrine transporter.

PMID- 9648876
TI  - Metabolic dysfunction in familial, but not sporadic, amyotrophic lateral
      sclerosis.
AB  - Autosomal dominant familial amyotrophic lateral sclerosis (FALS) is associated
      with mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1). Previous
      studies have implicated the involvement of metabolic dysfunction in ALS
      pathogenesis. To further investigate the biochemical features of FALS and
      sporadic ALS (SALS), we examined SOD activity and mitochondrial oxidative
      phosphorylation enzyme activities in motor cortex (Brodmann area 4), parietal
      cortex (Brodmann area 40), and cerebellum from control subjects, FALS patients
      with and without known SOD mutations, SALS patients, and disease controls (Pick's
      disease, progressive supranuclear palsy, diffuse Lewy body disease). Cytosolic
      SOD activity, predominantly Cu/Zn SOD, was decreased approximately 50% in all
      regions in FALS patients with SOD mutations but was not significantly altered in
      other patient groups. Marked increases in complex I and II-III activities were
      seen in FALS patients with SOD mutations but not in SALS patients. We also
      measured electron transport chain enzyme activities in a transgenic mouse model
      of FALS. Complex I activity was significantly increased in the forebrain of 60
      day-old G93A transgenic mice overexpressing human mutant SOD1, relative to levels
      in transgenic wild-type animals, supporting the hypothesis that the motor neuron
      disorder associated with SOD1 mutations involves a defect in mitochondrial energy
      metabolism.

PMID- 9648877
TI  - Ornithine decarboxylase in human brain: influence of aging, regional
      distribution, and Alzheimer's disease.
AB  - Although experimental animal data have implicated ornithine decarboxylase, a key
      regulatory enzyme of polyamine biosynthesis, in brain development and function,
      little information is available on this enzyme in normal or abnormal human brain.
      We examined the influence, in autopsied human brain, of postnatal development and
      aging, regional distribution, and Alzheimer's disease on the activity of
      ornithine decarboxylase. Consistent with animal data, human brain ornithine
      decarboxylase activity was highest in the perinatal period, declining sharply (by
      approximately 60%) during the first year of life to values that remained
      generally unchanged up to senescence. In adult brain, a moderately heterogeneous
      regional distribution of enzyme activity was observed, with high levels in the
      thalamus and occipital cortex and low levels in cerebellar cortex and putamen. In
      the Alzheimer's disease group, mean ornithine decarboxylase activity was
      significantly increased in the temporal cortex (+76%), reduced in occipital
      cortex (-70%), and unchanged in hippocampus and putamen. In contrast, brain
      enzyme activity was normal in patients with the neurodegenerative disorder
      spinocerebellar ataxia type I. Our demonstration of ornithine decarboxylase
      activity in neonatal and adult human brain suggests roles for ornithine
      decarboxylase in both developing and mature brain function, and we provide
      further evidence for the involvement of abnormal polyamine system activity in
      Alzheimer's disease.

PMID- 9648878
TI  - Pramipexole reduces reactive oxygen species production in vivo and in vitro and
      inhibits the mitochondrial permeability transition produced by the parkinsonian
      neurotoxin methylpyridinium ion.
AB  - Sporadic Parkinson's disease is associated with a defect in the activity of
      complex I of the mitochondrial electron transport chain. This electron transport
      chain defect is transmitted through mitochondrial DNA, and when expressed in host
      cells leads to increased oxygen free radical production, increased antioxidant
      enzyme activities, and increased susceptibility to programmed cell death.
      Pramipexole, a chemically novel dopamine agonist used for the treatment of
      Parkinson's disease symptoms, possesses antioxidant activity and is
      neuroprotective toward substantia nigral dopamine neurons in hypoxic-ischemic and
      methamphetamine models. We found that pramipexole reduced the levels of oxygen
      radicals produced by methylpyridinium ion (MPP+) both when incubated with SH-SY5Y
      cells and when perfused into rat striatum. Pramipexole also exhibited a
      concentration-dependent inhibition of opening of the mitochondrial transition
      pore induced by calcium and phosphate or MPP+. These results suggest that
      pramipexole may be neuroprotective in Parkinson's disease by attenuating
      intracellular processes such as oxygen radical generation and the mitochondrial
      transition pore opening, which are associated with programmed cell death.

PMID- 9648879
TI  - Oxidative damage to proteins, lipids, and DNA in cortical brain regions from
      patients with dementia with Lewy bodies.
AB  - Dementia with Lewy bodies (DLB) forms the second most common pathological
      subgroup of dementia after Alzheimer's disease. The present study compares the
      levels of oxidative damage to proteins, lipids, and DNA bases in cortical brain
      areas from patients with DLB with levels in matched control tissues. Overall,
      there was a trend for protein carbonyl levels to be increased in all areas, but a
      significant difference was found only in the parietal and temporal lobes. No
      differences were observed in the levels of lipid peroxidation. Measurement of
      products of damage to DNA bases showed increased levels of thymine glycol, 8
      hydroxyguanine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine, 5-hydroxycytosine, 5
      hydroxyuracil, 5-hydroxymethyluracil, and xanthine. Xanthine levels were
      increased in the DLB group in the parietal, occipital, and temporal lobes,
      indicating that peroxynitrite or other deaminating species may be involved. The
      finding of increased protein carbonyls and increased DNA base products in
      cortical regions from DLB patients indicates that oxidative stress may play a
      role in DLB.

PMID- 9648880
TI  - Mutant presenilin 2 transgenic mouse: effect on an age-dependent increase of
      amyloid beta-protein 42 in the brain.
AB  - The N141I missense mutation in presenilin (PS) 2 is tightly linked with a form of
      autosomal dominant familial Alzheimer's disease (AD) in the Volga German
      families. We have generated transgenic mouse lines overexpressing human wild-type
      or mutant PS2 under transcriptional control of the chicken beta-actin promoter.
      In the brains of transgenic mice, the levels of human PS2 mRNA were found to be
      five- to 15-fold higher than that of endogenous mouse PS2 mRNA. The amyloid beta
      protein (Abeta) 42 levels in the brains of mutant PS2 transgenic mice were higher
      than those in wild-type PS2 transgenic mice at the age of 2, 5, or 8 months. In
      addition, the Abeta42 levels appeared to increase steadily in the mutant PS2
      transgenic mouse brains from 2 to 8 months of age, whereas there was only a small
      increase in wild-type transgenic mice between the ages of 5 and 8 months. There
      was no definite difference in the levels of N-terminal and C-terminal fragments
      between wild-type and mutant PS2 transgenic mice at the age of 2, 5, or 8 months.
      These data show a definite effect of the PS2 mutation on an age-dependent
      increase of Abeta42 content in the brain.

PMID- 9648881
TI  - Enzymatic and molecular biological analysis of palmitoyl protein thioesterase
      deficiency in infantile neuronal ceroid lipofuscinosis.
AB  - Infantile neuronal ceroid lipofuscinosis (INCL) is a neurodegenerative lysosomal
      storage disease that results from a deficiency of palmitoyl protein thioesterase
      (PPT), a deacylating enzyme that removes cysteine-bound palmitate from proteins.
      We developed an in vitro PPT enzyme assay that can be readily used for the
      clinical diagnosis of both INCL patients and carriers. The substrate is a
      palmitoylated peptide (IRY[14C]palmitoyl-CWLRR) synthesized by reacting [14C]
      palmitoyl-CoA with a synthetic octapeptide from the PNS P0 glycoprotein. The PPT
      assay performed in immortalized lymphoblastoid B-cells or the postmortem brain
      homogenate showed the optimal enzyme activity at pH 5.0, consistent with the
      findings that PPT is a lysosomal enzyme. PPT activity in lymphoblasts from INCL
      patients was <4% of that of control lymphoblasts. In addition, obligatory
      carriers showed 74% of the control activity. Other pathological controls,
      including the juvenile form of NCL, showed PPT activities that were not different
      from normal. Furthermore, one brain sample from an INCL patient contained only 7%
      PPT activity when compared with an unaffected brain. Thus, the enzyme activity
      assay gives a confident diagnosis of INCL. In contrast, when the total RNA
      extract from lymphoblasts was probed with 32P-labeled PPT by northern blot
      analysis, the level of transcript varied among independent INCL families and was
      not related to PPT activity. In conclusion, whereas variant genetic modifications
      result in PPT deficiency, all giving similar INCL phenotype, both affected
      patients and heterozygote carriers can now be screened with a reliable in vitro
      PPT assay.

PMID- 9648882
TI  - Lactate is released and taken up by isolated rabbit vagus nerve during aerobic
      metabolism.
AB  - To determine if lactate is produced during aerobic metabolism in peripheral
      nerve, we incubated pieces of rabbit vagus nerve in oxygenated solution
      containing D-[U-14C]glucose while stimulating electrically. After 30 min, nearly
      all the radioactivity in metabolites in the nerve was in lactate, glucose 6
      phosphate, glutamate, and aspartate. Much lactate was released to the bath: 8.2
      pmol (microg dry wt)(-1) from the exogenous glucose and 14.2 pmol (microg dry
      wt)(-1) from endogenous substrates. Lactate release was not increased when bath
      PO2 was decreased, indicating that it did not come from anoxic tissue. When the
      bath contained [U-14C]lactate at a total concentration of 2.13 mM and 1 mM
      glucose, 14C was incorporated in CO2 and glutamate. The initial rate of formation
      of CO2 from bath lactate was more rapid than its formation from bath glucose. The
      results are most readily explained by the hypothesis that has been proposed for
      brain tissue in which glial cells supply lactate to neurons.

PMID- 9648883
TI  - Expression pattern of synucleins (non-Abeta component of Alzheimer's disease
      amyloid precursor protein/alpha-synuclein) during murine brain development.
AB  - The non-Abeta component of Alzheimer's disease amyloid precursor protein (NACP)
      is predominantly a neuron-specific presynaptic protein that may play a central
      role in neurodegeneration because NACP fragments are found in Alzheimer's disease
      amyloid and a mutation in the NACP gene is associated with familial Parkinson's
      disease. In addition, NACP may play an important role during synaptogenesis and
      CNS development. To understand better the patterns of NACP expression during
      development, we analyzed the levels of this protein as well as the levels of
      another synaptic protein (synaptophysin) by ribonuclease protection assay,
      western blotting, and immunocytochemistry in fetal, juvenile, and adult mouse
      brain. From embryonic day 12 to 15, there was a slight increase, which was then
      followed by a more dramatic increase at later time points. Immunocytochemical
      staining for NACP increases throughout these stages as well. Although NACP
      appeared early in CNS development, synaptophysin levels started to rise at a
      later stage. These findings support the contention that NACP might be important
      for CNS development. Furthermore, the cytosolic component of NACP precedes the
      particulate component in development, indicating that a redistribution of the
      protein to the membrane fraction may be important for events later in neuronal
      development and in synaptogenesis.

PMID- 9648884
TI  - Immunohistochemical localization of G protein beta1, beta2, beta3, beta4, beta5,
      and gamma3 subunits in the adult rat brain.
AB  - The regional distributions of the G protein beta subunits (Gbeta1-beta5) and of
      the Ggamma3 subunit were examined by immunohistochemical methods in the adult rat
      brain. In general, the Gbeta and Ggamma3 subunits were widely distributed
      throughout the brain, with most regions containing several Gbeta subunits within
      their neuronal networks. The olfactory bulb, neocortex, hippocampus, striatum,
      thalamus, cerebellum, and brainstem exhibited light to intense Gbeta
      immunostaining. Negative immunostaining was observed in cortical layer I for
      Gbeta1 and layer IV for Gbeta4. The hippocampal dentate granular and CA1-CA3
      pyramidal cells displayed little or no positive immunostaining for Gbeta2 or
      Gbeta4. No anti-Gbeta4 immunostaining was observed in the pars compacta of the
      substantia nigra or in the cerebellar granule cell layer and Purkinje cells.
      Immunoreactivity for Gbeta1 was absent from the cerebellar molecular layer, and
      Gbeta2 was not detected in the Purkinje cells. No positive Ggama3
      immunoreactivity was observed in the lateral habenula, lateral septal nucleus, or
      Purkinje cells. Double-fluorescence immunostaining with anti-Ggamma3 antibody and
      individual anti-Gbeta1-beta5 antibodies displayed regional selectivity with
      Gbeta1 (cortical layers V-VI) and Gbeta2 (cortical layer I). In conclusion,
      despite the widespread overlapping distributions of Gbeta1-beta5 with Ggamma3,
      specific dimeric associations in situ were observed within discrete brain
      regions.

PMID- 9648885
TI  - Synaptic vesicle protein SV2B, but not SV2A, is predominantly expressed and
      associated with microvesicles in rat pinealocytes.
AB  - Microvesicles are endocrine counterparts of neuronal synaptic vesicles, and
      accumulate and secrete classic neurotransmitters. In mammalian pinealocytes,
      microvesicles accumulate L-glutamate through a vesicular glutamate transporter
      and secrete it through exocytosis. To characterize the molecular organization of
      microvesicles in more detail, we investigated in this study the expression and
      localization of synaptic vesicle protein 2 (SV2) in rat pinealocytes. RT-PCR
      analysis indicated that transcripts specific for two isoforms, SV2A, a ubiquitous
      form present in neuronal and endocrine cells, and SV2B, a neuron-specific form,
      are amplified in pineal RNAs. Northern blotting with specific transcripts
      indicated that the mRNA for SV2B is predominantly expressed, whereas that for
      SV2A is below the detection limit. Site-specific antibodies against SV2B
      recognized a single 72-kDa polypeptide in the pineal membrane fraction, whereas
      anti-SV2A antibodies did not recognize any polypeptides. Immunohistochemical
      analysis of cultured cells indicated that SV2B is expressed in pinealocytes but
      not in other types of cells. SV2B is present in somata and is especially rich in
      processes, which are filled with microvesicles. SV2B is colocalized with
      synaptophysin and synaptotagmin, markers for microvesicles. Immunoelectron
      microscopy indicated that SV2B is associated with microvesicles. These results
      indicated that SV2B, but not SV2A, is expressed in rat pinealocytes and
      associated with microvesicles. As SV2B is also expressed in cultured alphaTC6
      clonal pancreatic a cells, SV2B is not a protein specific for neurons.

PMID- 9648886
TI  - Ceramide and its interconvertible metabolite sphingosine function as
      indispensable lipid factors involved in survival and dendritic differentiation of
      cerebellar Purkinje cells.
AB  - Ceramide generated from sphingomyelin has emerged as a new but conserved type of
      biologically active lipid. We previously found that endogenous sphingolipids are
      required for the normal growth of cultured cerebellar Purkinje neurons and that
      sphingomyelin is present abundantly in the somatodendritic region of these cells.
      To gain further insight into a potential role of the sphingomyelin/ceramide
      pathway, we investigated the effects of depletion of sphingolipids on the
      phenotypic growth and survival of immature Purkinje cells and the ability of
      ceramide or other sphingolipids to antagonize these effects. Inhibition of
      ceramide synthesis by ISP-1, a specific inhibitor of serine palmitoyltransferase,
      decreased cellular levels of sphingolipids. This treatment resulted in a decrease
      in cell survival accompanied by an induction of apoptotic cell death and aberrant
      dendritic differentiation of Purkinje cells with no detectable changes in other
      cerebellar neurons. Cell-permeable ceramides, sphingosine, or sphingomyelin
      overcame these abnormalities more effectively than other sphingolipids when added
      simultaneously with ISP-1. Exposure to bacterial sphingomyelinase in turn
      enhanced cell survival and dendritic branching complexity of Purkinje cells at
      different optimal concentrations. Furthermore, cell-permeable ceramide acted
      synergistically with the neurotrophin family, which has been previously shown to
      support Purkinje cell survival. These observations suggest that ceramide is a
      requisite for the survival and the dendritic differentiation of Purkinje cells.

PMID- 9648887
TI  - Regulation of Drosophila Ca2+/calmodulin-dependent protein kinase II by
      autophosphorylation analyzed by site-directed mutagenesis.
AB  - In this study we demonstrate that Drosophila calcium/calmodulin-dependent protein
      kinase II (CaMKII) is capable of complex regulation by autophosphorylation of the
      three threonines within its regulatory domain. Specifically, we show that
      autophosphorylation of threonine-287 in Drosophila CaMKII is equivalent to
      phosphorylation of threonine-286 in rat alpha CaMKII both in its ability to
      confer calcium independence on the enzyme and in the mechanistic details of how
      it becomes phosphorylated. Autophosphorylation of this residue occurs only within
      the holoenzyme structure and requires calmodulin (CaM) to be bound to the
      substrate subunit. Phosphorylation of threonine-306 and threonine-307 in the CaM
      binding domain of the Drosophila kinase occurs only in the absence of CaM, and
      this phosphorylation is capable of inhibiting further CaM binding. Additionally,
      our findings suggest that phosphorylation of threonine-306 and threonine-307 does
      not mimic bound CaM to alleviate the requirement for CaM binding to the substrate
      subunit for intermolecular threonine-287 phosphorylation. These results
      demonstrate that the mechanism of regulatory autophosphorylation of this kinase
      predates the split between invertebrates and vertebrates.

PMID- 9648888
TI  - The peptide transporter PepT2 mediates the uptake of the glutathione precursor
      CysGly in astroglia-rich primary cultures.
AB  - The intracellular content of glutathione in astroglia-rich primary cultures
      derived from the brains of newborn rats was used as an indicator for the ability
      of these cultures to utilize cysteinylglycine (CysGly) for glutathione synthesis.
      After a 24-h starvation period in the absence of glucose and amino acids, CysGly
      was able to substitute for cysteine plus glycine in the restoration of
      glutathione. Glutathione restoration from CysGly plus glutamate was only slightly
      affected by the dipeptides carnosine or serylglycine in a 200-fold excess.
      Captopril, a substrate of the peptide transporter PepT1, had almost no effect on
      glutathione restoration. In contrast, with increasing concentrations of
      alanylalanine or cefadroxil, known substrates of the peptide transporter PepT2,
      the amount of glutathione restored in the presence of CysGly and glutamate was
      strongly reduced. Cefadroxil in a 200-fold excess totally prevented the
      utilization of CysGly for glutathione restoration. The presence of mRNA for PepT2
      in astroglia-rich primary cultures was demonstrated by application of RT-PCR.
      These results demonstrate that PepT2 is expressed in astroglia-rich primary
      cultures and that this transporter is highly likely to be responsible for the
      uptake of CysGly in these cultures.

PMID- 9648889
TI  - Differential effects of increasing gestational age and placental restriction on
      tyrosine hydroxylase, phenylethanolamine N-methyltransferase, and proenkephalin A
      mRNA levels in the fetal sheep adrenal.
AB  - We have demonstrated that there are differential changes in the levels of
      tyrosine hydroxylase (TH), phenylethanolamine N-methyltransferase (PNMT), and
      proenkephalin A (Pro Enk A) mRNA in the fetal sheep adrenal during late
      gestation. Adrenal TH mRNA:18S rRNA ratios increased between gestational days 100
      (0.98 +/- 0.13; n = 6) and 125 (1.40 +/- 0.15; n = 6) and then decreased, whereas
      adrenal PNMT mRNA:18S rRNA ratios increased regularly between gestational days
      100 (0.08 +/- 0.01) and 146 (0.17 +/- 0.03). The ratio of adrenal Pro Enk A mRNA
      to 18S rRNA was higher at gestational day 125 (0.085 +/- 0.005) than at either 80
      100 days (0.038 +/- 0.007) or 140-146 days of gestation (0.055 +/- 0.013). In 12
      ewes, the growth and development of the placenta were restricted (placental
      restriction group) from conception. The ratio of adrenal PNMT mRNA to 18S rRNA
      was significantly reduced in the placental restriction group of fetal sheep
      (0.003 +/- 0.002) compared with controls (0.011 +/- 0.002), and there was a
      significant correlation between the ratio of adrenal PNMT mRNA to 18S rRNA and
      the mean arterial PO2 (r = 0.88, p < 0.0005). In contrast, TH mRNA and Pro Enk
      mRNA were unaffected by placental restriction. Adrenaline and noradrenaline
      syntheses are therefore differentially regulated in the adrenal during late
      gestation and in response to chronic intrauterine hypoxemia.

PMID- 9648890
TI  - Manipulation of disulfide bonds differentially affects the intracellular
      transport, sorting, and processing of neuroendocrine secretory proteins.
AB  - To investigate if the prevention of disulfide bond formation affects the
      intracellular transport, sorting, and processing of a distinct set of
      neuroendocrine proteins in the regulated secretory pathway, we have treated
      Xenopus intermediate pituitaries with the thiol-reducing agent dithiothreitol.
      Pulse-chase incubations in combination with immunoprecipitation analysis were
      used to monitor the fates of the prohormone proopiomelanocortin (POMC),
      prohormone convertase PC2 and its helper protein 7B2, as well as secretogranin
      III. Manipulation of the disulfide bonds in POMC and proPC2 blocked their
      transport to the trans-Golgi network and strongly inhibited their processing.
      Reduction of the single disulfide bond in 7B2 did not disturb its transport and
      cleavage, but caused its missorting to the constitutive secretory pathway.
      Moreover, the liaison between proPC2 and 7B2 was prevented. Dithiothreitol did
      not affect transport, sorting, and cleavage of secretogranin III, which lacks
      disulfide bonds. When the reducing agent was washed away, POMC processing, proPC2
      maturation, and the association between proPC2 and 7B2 were reestablished.
      Collectively, our findings indicate that manipulation of disulfide bonds
      differentially affects the fates of neuroendocrine proteins during their transit
      through the secretory pathway.

PMID- 9648891
TI  - Phosphatidic acid-dependent phosphorylation of a 29-kDa protein by protein kinase
      Calpha in bovine brain cytosol.
AB  - Activation of phospholipase D (PLD) is involved in receptor-mediated signal
      transduction responses. Signaling from PLD to a downstream molecule(s) appears to
      be mediated by the PLD product phosphatidic acid (PA). A target molecule(s) of
      PA, however, has not yet been identified. The present study sought to define such
      a target molecule(s) of PA. In bovine brain cytosol, proteins with apparent
      molecular weights of 29,000 (p29) and 32,000 (p32) were prominently
      phosphorylated in the presence of PA, but not in its absence, indicating that
      there is a PA-regulated protein kinase (PARK) in bovine brain that phosphorylates
      p29 and p32. One of these substrates, p29, was purified to near homogeneity. Its
      partial amino acid sequence was determined and found to be identical to that of a
      known brain-specific 25-kDa protein (p25). The purified p29 was also readily
      recognized by and immunoprecipitated with an anti-p25 antibody. These results
      suggest that p29 is very similar to or identical with p25. Using the purified p29
      as a substrate, PARK was purified to near homogeneity. The purified PARK had an
      apparent molecular weight of 80,000, was strongly recognized by an antiprotein
      kinase C (PKC)alpha antibody, and was activated by phosphatidylserine (PS) as
      well as PA. The PA- and PS-stimulated PARK activity was extremely augmented by
      the presence of 1 microM free Ca2+. In the presence of 1 mM EGTA, phorbol 12
      myristate 13-acetate activated PARK synergistically with PA or PS. Similar
      results were obtained with the purified recombinant PKCalpha. From these results,
      it is suggested that the PARK activity purified might be attributed to PKCalpha.
      In p25-depleted bovine brain cytosol, which was prepared by treatment of bovine
      brain cytosol with the anti-p25 antibody, PA-dependent phosphorylation of p29,
      but not p32, was almost completely eliminated. When PKCalpha in bovine brain
      cytosol was depleted by its precipitation with the anti-PKCalpha antibody,
      neither p29 nor p32 in this PKCalpha-depleted cytosol was phosphorylated in the
      presence of PA. These results indicate that in bovine brain cytosol PA activates
      PKCalpha, which, in turn, phosphorylates p29, which may be identical with p25.

PMID- 9648893
TI  - Dynamic regulation of the activated, autophosphorylated state of Ca2+/calmodulin
      dependent protein kinase II by acute neuronal excitation in vivo.
AB  - Ca2+/calmodulin-dependent protein kinase II (CaMKII) has been implicated in
      various neuronal functions, including synaptic plasticity. To examine the
      physiological regulation of its activated, autophosphorylated state in relation
      to acute neuronal excitation in vivo, we studied the effect of electroconvulsive
      treatment in rats on CaMKII activity and in situ autophosphorylation levels. As
      early as 30 s after the electrical stimulation, a profound but transient decrease
      in its Ca2+/calmodulin-independent activity, as well as in the level of its
      autophosphorylation at Thr286(alpha)/Thr287(beta) measured by using
      phosphorylation state-specific antibodies, was observed in homogenate from
      hippocampus and parietal cortex, which was reversible in 5 min. In the later time
      course, a moderate, reversible increase, which peaked at around 60 min after the
      electrical stimulation, was observed in parietal cortex but not in hippocampus.
      The early-phase decrease was found to occur exclusively in the soluble fraction.
      In addition, partial translocation of CaMKII from the soluble to the particulate
      fraction seems to have occurred in this early phase. Thus, the activated,
      autophosphorylated state of CaMKII is under dynamic and precise regulation in
      vivo, and its regulatory mechanisms seem to have regional specificity.

PMID- 9648892
TI  - Binding characteristics of a potent AMPA receptor antagonist [3H]Ro 48-8587 in
      rat brain.
AB  - A new AMPA receptor antagonist, Ro 48-8587, was characterized pharmacologically
      in vitro. It is highly potent and selective for AMPA receptors as shown by its
      effects on [3H]AMPA, [3H] kainate, and [3H] MK-801 binding to rat brain membranes
      and on AMPA- or NMDA-induced depolarization in rat cortical wedges. [3H]Ro 48
      8587 bound with a high affinity (KD = 3 nM) to a single population of binding
      sites with a Bmax of 1 pmol/mg of protein in rat whole brain membranes. [3H]Ro 48
      8587 binding to rat whole brain membranes was inhibited by several compounds with
      the following rank order of potency: Ro 48-8587 > 6-nitro-7-sulphamoylbenzo[f]
      quinoxaline-2,3-dione (NBQX) > YM 90K > 6-cyano-7-nitroquinoxaline-2,3-dione
      (CNQX) > quisqualate > AMPA > glutamate > kainate > NMDA. The distribution and
      abundance of specific binding sites (approximately 95% of total) in sections of
      rat CNS, revealed by quantitative receptor radioautography and image analysis,
      indicated a very discrete localization. Highest binding values were observed in
      cortical layers (binding in layers 1 and 2 > binding in layers 3-6), hippocampal
      formation, striatum, dorsal septum, reticular thalamic nucleus, cerebellar
      molecular layer, and spinal cord dorsal horn. At 1 nM, the values for specific
      binding were highest in the cortical layers 1 and 2 and lowest in the brainstem
      (approximately 2.6 and 0.4 pmol/mg of protein, respectively). Ro 48-8587 is a
      potent and selective AMPA receptor antagonist with improved binding
      characteristics (higher affinity, selectivity, and specific binding) compared
      with those previously reported.

PMID- 9648894
TI  - Norepinephrine increases cyclic GMP levels in cerebellar cells from neuronal
      nitric oxide synthase knockout mice.
AB  - Cyclic GMP is an important intracellular messenger in the nervous system that may
      mediate cellular forms of neuronal plasticity. Previous studies show that most
      neurotransmitters stimulate cyclic GMP levels by the activation of nitric oxide
      synthase (NOS). In this study, we report that in primary cell cultures from the
      cerebellum of neuronal NOS knockout mice, norepinephrine stimulates an increase
      in cyclic GMP content. This increase is seen in both granule cell and astrocyte
      cultures and is not blocked by inhibitors of NOS or by inhibition of soluble
      guanylyl cyclase. These results suggest a novel pathway by which norepinephrine
      enhances cyclic GMP levels in the nervous system.

PMID- 9648895
TI  - Examining amended reports in surgical pathology.

PMID- 9648896
TI  - Amended reports in surgical pathology and implications for diagnostic error
      detection and avoidance: a College of American Pathologists Q-probes study of
      1,667,547 accessioned cases in 359 laboratories.
AB  - OBJECTIVES: To evaluate amended report rates relative to surveillance methods and
      to identify surveillance methods or other practice parameters that lower amended
      report rates. DESIGN: Participants in the 1996 Q-Probes quality improvement
      program of the College of American Pathologists were asked to prospectively
      document amended surgical pathology reports for a period of 5 months or until 50
      amended reports were recorded. The methods of error detection were also recorded
      and laboratory and institutional policies surveyed. Four types of amended reports
      were investigated: those issued to correct patient identification errors, to
      revise originally issued final diagnoses, to revise preliminary written
      diagnoses, and to revise other reported diagnostic information that was
      significant with respect to patient management or prognosis. PARTICIPANTS: Three
      hundred fifty-nine laboratories, 96% from the United States. RESULTS: A total of
      3147 amended reports in all four categories from a survey of 1,667,547 surgical
      pathology specimens accessioned during the study period were issued by the
      participants. The aggregate mean rate of amended reports was 1.9 per 1000 cases
      (median, 1.5 per 1000 cases). Of these, 19.2% were issued to correct patient
      identification errors, 38.7% to change the originally issued final diagnosis,
      15.6% to change a preliminary written diagnosis, and 26.5% to change clinically
      significant information other than the diagnosis. Most frequently, a request from
      a clinician to review a case (20.5%) precipitated the error detection. Although
      not statistically significant, a higher amended report rate (1.6 per 1000) for
      all error types was associated with routine diagnostic slide review that was
      performed after completion of the surgical pathology report. This is compared to
      rates for institutions that had routine diagnostic slide review of cases prior to
      finalization of pathology reports (1.2 per 1000) and institutions that had no
      routine diagnostic slide review (1.4 per 100). Slide review of cases prior to
      completion of reports lowered the rate of amended reports issued for two types of
      amended reports: those in which the originally issued final diagnosis was changed
      and those in which information other than the diagnosis was changed for patient
      management or prognostic significance. Other laboratory practice variables
      examined were not found to be associated with the amended report rate.
      CONCLUSIONS: There is an association between lower amended report rates and
      diagnostic slide review of cases prior to completion of the pathology report. The
      level of case review and type of case mix that is necessary for optimal quality
      assurance needs further investigation.

PMID- 9648897
TI  - Apoptosis: basic concepts and potential significance in human cancer.
AB  - Numerous factors trigger or repress apoptosis (genetically mediated individual
      cell death). The details of signal transduction pathways and regulation of
      apoptosis by numerous oncogene and tumor suppressor gene products are not fully
      understood. Bcl-2 inhibits apoptosis induction by a variety of stimuli. Caspases
      are the basic effectors of apoptosis, leading ultimately to fragmentation of DNA,
      at which stage apoptosis can be identified. Apoptosis affects scattered
      individual cells that have extremely dense nodular, beaded, or crescentic
      chromatin, and differs morphologically, biochemically, and topographically from
      necrosis. Apoptosis is a negative growth-regulating mechanism in cancer, and its
      extent varies with tumor type. Apoptosis reflects tumor cell kinetics; aggressive
      tumors often show conspicuous apoptosis, and there are significant linear
      correlations between apoptotic and mitotic indices in many tumor types. The
      relative importance of p53, c-Myc, Rb, and the Bcl-2 homologs in the regulation
      of apoptosis in different human cancers is not clear. Further pathologic
      investigations on apoptosis in human cancer are needed to reaffirm recent
      experimental findings and to explain more fully the regulation and biological
      significance of apoptosis in vivo.

PMID- 9648898
TI  - Evaluation of a proposed panel of cardiac markers for the diagnosis of acute
      myocardial infarction in patients with atraumatic chest pain.
AB  - OBJECTIVE: The purpose of this study was to evaluate retrospectively the efficacy
      of a proposed panel of three cardiac markers (myoglobin, creatine kinase-MB mass
      [CK-MB], and cardiac troponin I) in the diagnosis of acute myocardial infarction
      (AMI) in patients with atraumatic chest pain. DESIGN: A total of 110 patients
      admitted for the evaluation of atraumatic chest pain were examined. Forty-one of
      these patients were diagnosed with AMI. RESULTS: Five of the 41 patients with AMI
      had abnormally elevated myoglobin levels, whereas values of CK-MB and/or cardiac
      troponin I remained negative. Creatine kinase-MB mass alone had a sensitivity of
      92.7%, a specificity of 89.9%, a positive predictive value of 84.4%, and a
      negative predictive value of 95.0% for the diagnosis of AMI. Cardiac troponin I
      alone had a sensitivity of 90.2%, a specificity of 95.7%, a positive predictive
      value of 92.5%, and a negative predictive value of 94.3% for the diagnosis of
      AMI. Cardiac troponin I is a more specific marker for the diagnosis of AMI than
      CK-MB, particularly in patients with chronic renal failure who are evaluated for
      chest pain. The combination of CK-MB and cardiac troponin I increased the
      sensitivity to 100% and the negative predictive value to 100% and had a
      specificity of 88.4% and a positive predictive value of 83.7%. The panel was
      diagnostic for all patients with AMI within 12 hours after admission.
      CONCLUSIONS: Our preliminary results indicate that this panel is highly effective
      for evaluation of AMI in patients with atraumatic chest pain. Elevated myoglobin
      levels were useful in detecting patients at high risk for AMI who initially were
      not detected with other markers. The combination of CK-MB and cardiac troponin I
      provided much higher sensitivity and had a much higher negative predictive value
      for the evaluation of AMI than cardiac troponin I or CK-MB alone. The 100%
      negative predictive value is particularly important because it indicates that
      patients with negative CK-MB and cardiac troponin I values 12 hours after
      admission have a negligible likelihood of AMI.

PMID- 9648899
TI  - Comparison of functional testing for resistance to activated protein C and
      molecular biological testing for factor V R506Q in 370 patients.
AB  - OBJECTIVE: To compare functional and molecular biological tests for resistance to
      activated protein C (APC)/factor V R506Q, the most common cause of familial
      thrombosis. METHODS: We developed functional and molecular biological tests for
      resistance to APC/factor V R506Q at our institution and correlated the results
      for 370 patients studied by both methods. The functional method is based on
      addition of exogenous APC to an activated partial thromboplastin time-based
      assay. The molecular biological method is based on polymerase chain reaction
      followed by endonuclease digestion. RESULTS: Considering the molecular biological
      test as definitive for detecting the factor V R506Q mutation, the sensitivity of
      the functional assay was 100%, and the specificity was 74%. The prevalence of the
      factor V mutation in the population studied was 12% (41 heterozygotes, two
      homozygotes), and the positive predictive value of the functional assay was 34%.
      Although a normalized sensitivity ratio (nAPC-SR) less than 0.84 is considered
      evidence of resistance to APC by functional testing, we found that all patients
      with factor V R506Q had an nAPC-SR less than or equal to 0.71. When this
      alternative positive cutoff was used, the specificity of the functional test for
      factor V R506Q increased to 87%, and the positive predictive value increased to
      52%, which constituted a significant improvement. We compared clinical findings
      from patients with resistance to APC with or without the presence of factor V
      R506Q, and found that as a group, those with factor V R506Q had a higher
      incidence of hypercoagulability, but fewer additional risk factors for
      hypercoagulability. The mechanism of resistance to APC in factor V R506Q-negative
      individuals is unclear, but may be related to other risk factors for
      hypercoagulability. CONCLUSIONS: The functional assay for resistance to APC is an
      excellent screening test for factor V R506Q, but confirmatory molecular
      biological testing is necessary when the functional test is positive, because of
      the high false-positive rate.

PMID- 9648900
TI  - Use of age-specific normal ranges for serum prostate-specific antigen.
AB  - BACKGROUND: The traditional normal range for prostate-specific antigen has been
      0.0 to 4.0 ng/mL. Two different age-specific normal ranges have been proposed,
      one by Oesterling et al and the other generated by the Prostate Cancer Awareness
      Week experience. METHODS: We studied 213 consecutive cases of biopsy-proven
      prostate adenocarcinoma to evaluate age-specific normal ranges for prostate
      specific antigen. We examined each patient's age, stage of disease, and serum
      concentration of prostate-specific antigen at the time of diagnosis. The three
      normal ranges were applied to each case. RESULTS: The patients ranged in age from
      45 to 87 years. At all stages of disease, more patients had elevated serum
      prostate-specific antigen values using the traditional normal range as opposed to
      either age-specific normal range. These discrepancies were most obvious for stage
      II disease, in which 93 of 119 cases (78%) were elevated according to the
      traditional normal range versus 78 of 119 cases (66%) according to the Oesterling
      et al range and 80 of 119 cases (67%) according to the range defined during
      Prostate Cancer Awareness Week. For patients aged 40 to 59 years, all three
      normal ranges provided identical results (18 of 22 [82%] cancers detected).
      CONCLUSIONS: Use of either age-specific normal range would have missed more than
      10% of stage II prostate adenocarcinomas in patients over the age of 60 years.
      This indicates that caution should be exercised when applying age-adjusted normal
      ranges for serum concentrations of prostate-specific antigen in patients of that
      age group.

PMID- 9648901
TI  - Cytologic and genetic study of polyomavirus-infected or polyomavirus-activated
      cells in human urine.
AB  - OBJECTIVE: To carry out a morphologic and genetic study of human polyomavirus
      infection or activation in child and adult urine specimens. DESIGN AND SETTING:
      The study was carried out on 16 urine samples from children with human
      polyomavirus infection and 104 samples from adults with virus activation
      identified among 18800 consecutive urine samples (0.64%). RESULTS: All specimens
      from children showed numerous typical intranuclear inclusion-bearing (INIB)
      cells. All adult specimens with cytological features similar to childhood
      specimens were defined as type 1 adult cases. We identified 14 adult cases with
      marked immunologic suppression as type 1 cases. The inclusions were large,
      homogeneous, and basophilic, and they were mainly attributable to the BK virus,
      as demonstrated by a polymerase chain reaction. These infected or activated cells
      revealed features demonstrating their origin in the superficial transitional
      epithelium of the urinary tract. Adult cases with different cytologic features
      were designated as type 2 adult cases. In type 2 adult cases, the number of virus
      activated cells was lower, and degenerated intranuclear inclusion-bearing cells
      with a coarse chromatin pattern were observed in most cases. These
      characteristics were identified in 90 adults without immunologic suppression. A
      polymerase chain reaction with BamHI digestion demonstrated JC virus DNA in
      nearly all of these specimens. CONCLUSION: The JC virus-activated cells found in
      type 2 adult cases and the BK virus-infected cells found in childhood cases were
      not of clinical importance. However, the BK virus-activated cells associated with
      immunologic suppression may have prognostic significance.

PMID- 9648902
TI  - Qualifying the cytologic diagnosis of "atypical squamous cells of undetermined
      significance" affects the predictive value of a squamous intraepithelial lesion
      on subsequent biopsy.
AB  - OBJECTIVE: To evaluate whether different qualifications of a cytologic diagnosis
      of "atypical squamous cells of undetermined significance" predict a greater or
      lesser likelihood of cervical pathology. DESIGN: Comparison of different
      cytologic qualifications of atypical squamous cells of undetermined significance
      with the frequency of significant cervical disease as documented by tissue
      biopsy. PARTICIPANTS AND SETTING: Four hundred, fifty-two consecutive
      Papanicolaou smears showing atypical squamous cells of undetermined significance
      (diagnosed by nine cytopathologists) in women who had undergone cervical biopsy
      within the previous 90 days at Brigham and Women's Hospital, Boston, Mass
      (January-June 1995). MAIN OUTCOME MEASURE: The histopathologic diagnosis of
      squamous intraepithelial lesion of the cervix. RESULTS: The 452 smears were
      qualified as "favor reactive" (22%), "not otherwise specified" (42%), "favor
      squamous intraepithelial lesion" (29%), and "favor high-grade squamous
      intraepithelial lesion" (6%). High-grade squamous intraepithelial lesions and
      total squamous intraepithelial lesions were pathologically confirmed by cervical
      biopsy in 3.6% and 6% of the favor reactive smears, in 11% and 21% of the not
      otherwise specified smears, in 12% and 30% of the favor squamous intraepithelial
      lesion smears, and in 53% and 59% of the favor high-grade squamous
      intraepithelial lesion smears. Significant associations were seen between a favor
      reactive smear and a benign finding on cervical biopsy (94%, P = .04) and between
      a favor high-grade squamous intraepithelial lesion smear and a biopsy that showed
      a high-grade squamous intraepithelial lesion (53%, P = .00001). CONCLUSIONS:
      Qualifying atypical squamous cells of undetermined significance stratifies women
      into different risk groups for squamous intraepithelial lesion. It is reasonable
      for physicians to make patient management decisions based, at least in part, on
      such qualifications.

PMID- 9648903
TI  - The histologic effects of low-dose methotrexate therapy for primary biliary
      cirrhosis.
AB  - OBJECTIVE: Primary biliary cirrhosis is a progressive liver disease that is
      believed to be autoimmune in nature. Treatment, at best, may slow the progression
      of the disease, although no therapy has been able to halt its progression.
      Preliminary data suggest a beneficial effect of methotrexate in the treatment of
      primary biliary cirrhosis. We evaluated the histologic effect of 2 years of
      treatment with methotrexate. DESIGN: Liver biopsies were obtained before
      methotrexate was started and after 2 years of therapy. Ninety-six paired biopsies
      from 48 patients with primary biliary cirrhosis were reviewed by a pathologist
      who was blinded to all clinical history and sequence of the biopsies. Variables
      examined included stage of the disease, degree of portal fibrosis, portal
      inflammation and piecemeal necrosis, bile duct injury or loss, bile ductular
      proliferation, lobular inflammation and necrosis, steatosis, granulomas,
      cholestasis, and nuclear pleomorphism of hepatocytes. RESULTS: In most
      categories, pretreatment and posttreatment biopsies did not reflect a change over
      the 2-year period of treatment. There was a trend toward progression of the stage
      of the disease, portal fibrosis, bile duct loss, fat, and pleomorphism over the 2
      years and toward regression in piecemeal necrosis, bile duct injury, ductular
      proliferation, granulomas, and lobular inflammation and necrosis. CONCLUSION:
      After 2 years of treatment with methotrexate, the stage of disease and fibrosis
      of primary biliary cirrhosis continue to progress, although overall, inflammation
      and bile duct injury decrease with methotrexate treatment.

PMID- 9648904
TI  - Comparative study of computer-assisted image analysis and light-microscopically
      determined estrogen receptor status of breast carcinomas.
AB  - BACKGROUND: Efficient tamoxifen treatment of breast cancer patients depends on
      the degree to which pathologists are consistently able to use the so-called
      "modified quickscore" method to differentiate between negative and low-grade
      positive scores based on the current four-grade scale of the estrogen receptor
      (ER) status of the tumors. OBJECTIVE: To quantitatively test pathologists'
      ability to adequately render correct readings of the ER status of breast tumors.
      METHODS: The ER status of breast carcinomas was estimated by two pathologists and
      measured by computer-supported analysis in sections stained with ER antibody by
      the immunoperoxidase technique. Levels of agreement between the examiners'
      semiquantification and histomorphometrically gauged measurements were compared
      statistically. RESULTS: The kappa coefficients were 0.28 on a case-by-case
      collation of the grades of nuclear staining, 0.52 on applying binary categories
      of positively versus negatively stained cell nuclei, and 0.89 using binary
      categories with a weighted score of 1.2 to separate ER-negative from ER-positive
      breast carcinomas. CONCLUSIONS: The findings suggest that an optimum rating
      system is achieved by assigning tumors with a weighted score of 1.2 or less to
      the ER-negative and those with a weighted score of 1.3 or more to the ER-positive
      category of breast carcinomas.

PMID- 9648905
TI  - Glycogen-rich malignant melanomas and glycogen-rich balloon cell malignant
      melanomas: frequency and pattern of PAS positivity in primary and metastatic
      melanomas.
AB  - OBJECTIVE: After identifying a metastatic glycogen-rich balloon cell malignant
      melanoma, originally thought to be a benign clear cell tumor of the lung, we
      investigated the extent of positive reactions, or "positivity," of malignant
      melanoma to periodic acid-Schiff (PAS) staining. METHODS: Frequency, intensity,
      and distribution of PAS positivity was studied in 61 excisional biopsy specimens
      from 58 patients with malignant melanoma. For comparison, 17 benign nevi from 10
      patients were examined. RESULTS: Positivity for PAS was seen in all cases. All
      malignant melanomas and benign nevi were characterized by weak, diffuse, diastase
      resistant PAS positivity. Additionally, focal or diffuse, strong diastase
      sensitive PAS positivity was observed in 9 of 61 melanomas (15%); 7 were
      metastatic and 2 were primary invasive melanomas. Strong diastase-sensitive PAS
      positivity was seen in all lesions with 30% or more balloon cell features and
      only in advanced primary or metastatic lesions. The presence of glycogen was
      confirmed by transmission electron microscopy. CONCLUSIONS: Cutaneous malignant
      melanomas have weak, diastase-resistant PAS positivity. Strong diastase-sensitive
      PAS positivity, consistent with the presence of intracytoplasmic glycogen, is
      seen in many primary and metastatic melanomas with balloon cell features.
      Depending on the content of the balloon cells, these melanomas are best
      categorized as either glycogen-rich malignant melanomas or glycogen-rich balloon
      cell malignant melanomas. Because many tumors with clear cell features contain
      glycogen, such content often is an unreliable differential feature.

PMID- 9648906
TI  - Primary T-cell lymphoma of the brain in a patient at advanced stage of acquired
      immunodeficiency syndrome.
AB  - OBJECTIVE: To present, to our knowledge, the first case of primary central
      nervous system T-cell lymphoma in the setting of acquired immunodeficiency
      syndrome. Design.Clinical, radiological, laboratory, and pathological data from a
      young patient at advanced stage of acquired immunodeficiency syndrome were
      studied. RESULTS: A 38-year-old white man with stage CIII human immunodeficiency
      virus infection presented with headaches. Cerebrospinal fluid culture was
      positive for mycobacterium. He had facial herpes simplex virus and disseminated
      cytomegalovirus infections. Magnetic resonance imaging of the brain showed
      multiple areas of patchy or ring-shaped contrast enhancement in the
      periventricular zone of the right frontoparietal region. Stereotactic brain
      biopsy showed perivascular CD3 (pan T-cell marker)-positive lymphocytic
      infiltrates with partial necrosis extending into the neuropil. Not a single cell
      was labeled with L26, a B-cell marker. Negative and positive controls were
      appropriate. Special stains for cytomegalovirus, herpes simplex virus, Epstein
      Barr virus, acid-fast bacilli, and fungi were negative. Gene rearrangement
      studies showed rearranged Tgamma and Tbeta bands. Polymerase chain reaction with
      a primer specific for Epstein-Barr virus genome-encoding nuclear antigen 1 region
      was positive. Human T-cell leukemia/lymphoma virus I work-up was negative. The
      patient was treated for mycobacteria. Four months later, he presented with a
      paravertebral neck mass. Needle biopsy showed a T-cell lymphoma with morphology
      similar to that in the brain. CONCLUSIONS: To our knowledge, this case represents
      the first example of T-cell lymphoma of the brain in a patient with advanced
      stage of acquired immunodeficiency syndrome. Epstein-Barr virus may play a role
      in T-cell lymphomagenesis. The other unique finding is the complete absence of B
      cells in a central nervous system lesion. The underlying mechanism eradicating
      the B cells is unknown.

PMID- 9648907
TI  - Perineurioma with ossification: a case report with immunohistochemical and
      ultrastructural studies.
AB  - We present the case of a peripheral nerve sheath tumor arising from the sciatic
      nerve in the thigh of a 42-year-old woman. Histologically, the tumor was composed
      of fascicles of spindle cells with extremely attenuated cytoplasmic processes.
      Regions of the tumor were heavily mineralized and fibrotic. The tumor was
      epithelial membrane antigen-positive and S100-negative. Staining for Leu-7 was
      positive in a patchy distribution. Type IV collagen was present between cells,
      and CD34 was negative in the tumor cells. Ultrastructural features included
      elongate cellular processes surrounded by discontinuous basal lamina and
      collagen. The features of the tumor therefore meet criteria for perineurioma.
      This rare tumor is found most often in the extremities in middle-aged woman. To
      our knowledge, the presence of bone formation in a perineurioma has not been
      described previously. The differential diagnosis includes other peripheral nerve
      sheath tumors, low-grade fibrous tumors, and synovial (monophasic) tumors.
      Evidence provided by electron microscopy and immunohistochemistry supports the
      diagnosis and classification of this unusual nerve sheath tumor as perineurioma
      with ossification. These findings expand our knowledge and criteria for
      classifying peripheral nerve sheath tumors.

PMID- 9648908
TI  - Recurrence of unicystic ameloblastoma: a case report and review of the
      literature.
AB  - Unicystic ameloblastoma is believed to be less aggressive and responds more
      favorably to conservative surgery than the solid or multicystic ameloblastomas.
      We report a case of unicystic ameloblastoma that was initially treated by
      marsupialization and later by enucleation under suspicion of a dentigerous cyst.
      The neoplastic nature of the lesion became evident only when the enucleated
      material was available for histologic examination. Apart from an
      ameloblastomatous epithelial lining and luminal tumor nodules, the cystic tumor
      contained numerous tumor islands within its fibrous capsule. The lesion recurred
      8 years after the enucleation. This case supports the view that the presence of
      tumor islands in the fibrous capsule may indicate a high risk of recurrence for
      unicystic ameloblastomas. Relevant diagnostic problems and choice of treatment
      are presented along with a review of the literature.

PMID- 9648909
TI  - Rhabdomyosarcoma mimicking acute leukemia in an adult: report of a case with
      histologic, flow cytometric, cytogenetic, immunohistochemical, and
      ultrastructural studies.
AB  - A case of a 25-year-old man who presented with low back, knee, and hip pain with
      bruising, leukocytosis, and thrombocytopenia is reported. Histopathologic and
      flow cytometric studies revealed a malignant neoplasm, which was thought to be
      consistent with an unusual type of acute leukemia. Subsequent immunohistochemical
      studies revealed diffuse bone marrow involvement by rhabdomyosarcoma,
      demonstrated by positivity for desmin and muscle-specific actin. In addition, the
      diagnosis of metastatic rhabdomyosarcoma was confirmed with cytogenetic and
      ultrastructural studies. The incidence of rhabdomyosarcoma, a disease usually
      seen in childhood, presenting with extensive bone marrow involvement and
      mimicking acute leukemia in an adult is extremely rare. This case highlights the
      need to consider rhabdomyosarcoma in the differential diagnosis in patients who
      present with a leukemic picture and atypical blasts that lack the usual
      hematopoietic markers.

PMID- 9648910
TI  - Virally activated Ras cooperates with integrin to induce tubulogenesis in
      sinusoidal endothelial cell lines.
AB  - Four cell lines, named nonparenchymal 11 (NP11), NP26, NP31, and NP32, were
      established from sinusoidal endothelial cells (SECs) of rat liver. They still
      retained expression of receptors for vascular endothelial growth factor (VEGF),
      Fit-1, and kinase domain-containing receptor (KDR). NP31 and NP32 turned out to
      be incapable of tubulogenesis in basement membrane matrix (Matrigel), which
      belongs to endothelial properties, as shown by SECs in primary culture.
      Expression of temperature-sensitive, virally activated Ras (ts-v-Ras) restored
      tubulogenic behaviors back to NP31 only at permissive temperature. Matrigel
      induced long-lasting tyrosine phosphorylation of Shc, with recruitment of Grb-2
      and microtubule-associated protein kinase (MAPK) activation in both parental NP31
      and NP31 transformed by ts-v-Ras, which was blocked by anti-beta1 integrin
      antibody. Tubulogenesis was inhibited by adenovirus-mediated expression of
      dominant-negative Ras in human umbilical vein endothelial cells (HUVECs). PD
      098059, a selective inhibitor of MAPK kinase (MEK), nearly perfectly blocked
      tubulogenesis by ts-v-Ras-expressing NP31 cells at permissive temperature.
      Furthermore, the botulinum C3 toxin, an inhibitor for Rho, caused fragmentation
      of branching cords in networks formed by NP31 that expressed ts-v-Ras at
      permissive temperature. These data suggest that the integrin-mediated Ras signals
      may be necessary but are not sufficient for tubulogenesis and that an artificial
      expression of v-Ras might substitute for the second signal required in this
      system.

PMID- 9648911
TI  - Induction of Ets-1 in endothelial cells during reendothelialization after
      denuding injury.
AB  - Ets-1, a transcription factor, is induced in endothelial cells (ECs) during
      angiogenesis. Here, we investigated the expression of Ets-1 during
      reendothelialization. When a confluent monolayer of human umbilical vein
      endothelial cell line, ECV304, was denuded, ECV304 at the wound edge expressed
      Ets-1. An immunohistochemical analysis revealed that Ets-1 accumulated in
      migrating cells at the wound edge and returned to basal level when
      reendothelialization was accomplished. This induction of Ets-1 could be
      reproduced in in vivo denudation of rat aortic endothelium by a balloon catheter.
      The induction of Ets-1 in ECs after denudation was regulated transcriptionally,
      and humeral factors released from injured ECs might not be responsible. Mitogen
      activated protein kinase (MAPK) activities were investigated to explore the
      mechanism of this induction. Although extracellular signal-regulated protein
      kinase 1/2 (ERK1/2), c-Jun N-terminal kinase 1 (JNK1), and p38 were activated
      after denudation, the activation of ERK1 and p38 was more rapid and prominent.
      PD98059, a specific MAPK/ERK kinase (MEK) 1 inhibitor, did not affect the
      induction of ets-1 mRNA, whereas SB203580, a specific p38 inhibitor, almost
      completely abrogated its induction. These results indicate that Ets-1 is induced
      in ECs after denudation through activation of p38. This induction of Ets-1 may be
      relevant for reendothelialization by regulating the expression of certain genes.

PMID- 9648912
TI  - Staurosporine-induced versus spontaneous squamous metaplasia in pre- and
      postmenopausal breast tissue.
AB  - Breast cancers from pre- vs. postmenopausal women display unique characteristics
      that may be related to differences in epithelial differentiation between these
      two populations. In addition to lobular development, lactational changes, and
      involution, breast epithelium can undergo metaplastic alterations, often in
      association with carcinoma. Because protein kinase C (PKC) regulates
      differentiation and proliferation in many cell types, we asked whether modulation
      of PKC activity could define biochemical differences in breast epithelium from
      pre- vs. postmenopausal women. Organ cultures of normal human breast were treated
      with PKC agonists and antagonists. Epithelial differentiation was evaluated based
      on morphologic criteria and the expression of cell-type specific proteins.
      Staurosporine, a nonspecific but extremely potent inhibitor of PKC, induced
      squamous metaplasia in eight of eight cases within 2 weeks of treatment. Other
      inhibitors of PKC, such as calphostin C and tamoxifen, had no effect on
      epithelial differentiation. Long-term treatment with phorbol esters also did not
      induce squamous metaplasia. However, stimulation of cAMP levels by forskolin and
      isobutyl-methyl-xanthene (IMX) rapidly induced squamous metaplasia, as has been
      previously reported. Surprisingly, squamous metaplasia occurred in 10 of 12
      cultures derived from postmenopausal women in the absence of exogenous agents.
      Untreated cultures derived from premenopausal women never developed this type of
      epithelium (0 of 11). Therefore, breast epithelium from pre- and postmenopausal
      women responded differently to in vitro culture. Forskolin/IMX or staurosporine
      can reproduce these conditions, acting independent of menopausal status. Because
      staurosporine's action was unique among PKC inhibitors, staurosporine may induce
      squamous metaplasia of breast epithelium by a PKC-independent mechanism.

PMID- 9648913
TI  - Epidermal growth factor (EGF)- and scatter factor/hepatocyte growth factor
      (SF/HGF)- mediated keratinocyte migration is coincident with induction of matrix
      metalloproteinase (MMP)-9.
AB  - Receptor tyrosine kinases are key regulators of cellular function including cell
      growth, differentiation, migration, and morphogenesis. Disruptions of receptor
      tyrosine kinase signaling pathways are often associated with changes in cellular
      proliferative capacity and tumorigenesis. Both receptor-specific and cell type
      specific factors may contribute to the ultimate cellular responses observed after
      receptor activation. In this regard, we find that both normal keratinocytes and
      their tumorigenic counterparts display differential responses to activation of
      receptor tyrosine kinases. Multiple ligands were mitogenic for keratinocytes, but
      only epidermal growth factor (EGF), transforming growth factor alpha (TGFalpha),
      and scatter factor/hepatocyte growth factor (SF/HGF) promoted cell motility as
      assessed by colony dispersion (scattering) and in vitro reepithelialization.
      Interestingly, growth factor specificity for motility coincided with ligand
      mediated cell invasion through a reconstituted basement membrane and induction of
      the 92-kDa metalloproteinase (MMP-9) activity as determined by gelatin zymogram
      analysis. Inhibitors of MMP activity or addition of an MMP-9 neutralizing
      antibody resulted in the loss of growth factor-induced colony dispersion,
      suggesting a functional role for MMP-9 induction during this response. Coordinate
      regulation of MMP-9 induction and the migratory response are likely to contribute
      to the enhanced invasive potential observed in response to EGF and SF/HGF. Our
      findings suggest that alternate receptor-mediated signaling pathways leading to
      differences in gene expression may be involved in complex cellular responses such
      as colony dispersion or invasion.

PMID- 9648914
TI  - Selective modulation of MAP kinase in embryonic palate cells.
AB  - Murine embryonic palate mesenchyme (MEPM) cells are responsive to a number of
      endogenous factors found in the local embryonic tissue environment. Recently, it
      was shown that activation of the cyclic AMP (cAMP) or the transforming growth
      factor beta (TGFbeta) signal transduction pathways modulates the proliferative
      response of MEPM cells to epidermal growth factor (EGF). Since the mitogen
      activated protein kinase (MAPK) cascade is a signal transduction pathway that
      mediates cellular responsiveness to EGF, we examined the possibility that several
      signaling pathways which abrogate EGF-stimulated proliferation do so via the
      p42/p44 MAPK signaling pathway. We demonstrate that EGF stimulates MAPK
      phosphorylation and activity in MEPM cells maximally at 5 minutes. Tyrosine
      phosphorylation and activation of MAPK was unaffected by treatment of MEPM cells
      with TGFbeta or cholera toxin. Similarly, TGFbeta altered neither EGF-induced
      MAPK tyrosine phosphorylation nor activity. However, the calcium ionophore,
      A23187, significantly increased MAPK phosphorylation which was further increased
      in the presence of EGF, although calcium mobilization reduced EGF-induced
      proliferation. Despite the increase in phosphorylation, we could not demonstrate
      induction of MAPK activity by A23187. Like EGF, phorbol ester, under conditions
      which activate PKC isozymes in MEPM cells, increased MAPK phosphorylation and
      activity but was also growth inhibitory to MEPM cells. The MEK inhibitor,
      PD098059, only partially abrogated EGF-induced phosphorylation. Likewise,
      depletion of PKC isozymes partially abrogated EGF-induced MAPK phosphorylation.
      Inhibition of both MEK and PKC isozymes resulted in a marked decrease in MAPK
      activity, confirming that EGF uses multiple pathways to stimulate MAPK activity.
      These data indicate that the MAPK cascade does not mediate signal transduction of
      several agents that inhibit growth in MEPM cells, and that there is a
      dissociation of the proliferative response and MAP kinase activation.
      Furthermore, other signaling pathways known to play significant roles in
      differentiation of palatal tissue converge with the MAPK cascade and may use this
      pathway in the regulation of alternative cellular processes.

PMID- 9648915
TI  - CD77-dependent retrograde transport of CD19 to the nuclear membrane: functional
      relationship between CD77 and CD19 during germinal center B-cell apoptosis.
AB  - A region of the N-terminal extracellular domain of the B-cell restricted cell
      differentiation antigen, CD19, has high amino acid sequence similarity to the
      receptor binding subunit B of verotoxin 1 (VT), an Escherichia coli elaborated
      cytotoxin, which specifically binds to the cell surface glycolipid,
      globotriaosylceramide, also known as the germinal center (GC) B-cell
      differentiation antigen, CD77. We have previously provided evidence of the
      association of CD19 and CD77 on the cell surface and in CD19-mediated homotypic
      adhesion of the Daudi Burkitt Lymphoma cell line, one normal counterpart of which
      is a subset of GC B cells. Evidence for the role of CD77 in CD19-induced
      apoptosis is now presented. Initial cell surface distribution, antibody-induced
      redistribution, internalization, and intracellular routing of CD19 were studied
      by confocal microscopy, IF, and postembedding IEM in CD77+ve and CD77-ve cells to
      investigate the possible role of CD77 in CD19 internalization and signaling.
      Daudi Burkitt's lymphoma cells were used as CD77+ve cells and as CD77-ve cells,
      Daudi mutant VT500 cells, and Daudi cells treated with PPMP, an inhibitor of CD77
      synthesis, were used. Antibody ligated CD19 surface redistribution,
      internalization, and subcellular distribution of internalized CD19 was found to
      be different in CD77+ve and CD77-ve cells. A delay in internalization of antibody
      CD19 complex was observed in CD77-ve cells. Internalized CD19 was targeted to the
      nuclear envelope in CD77+ve cells in a manner similar to that reported for VT,
      but not in CD77-ve cells. Internalization of CD77 by ligation with verotoxin
      prevented the internalization of ligated CD19. Induction of apoptosis following
      crosslinking of cell surface CD19 was greater in CD77+ve cells than in CD77-ve
      cells. The nuclear targeting of internalized CD19 and induction of apoptosis
      following CD19 crosslinking only in CD77+ve cells indicates a role for CD77
      dependent CD19 retrograde transport from the B cell surface via the ER to the
      nuclear envelope in CD19-mediated signal transduction for apoptosis.

PMID- 9648916
TI  - Cell shape-dependent pathway of plasminogen activator inhibitor type-1 gene
      expression requires cytoskeletal reorganization.
AB  - Synthesis of plasminogen activator inhibitor type-1 (PAI-1), a major
      physiological modulator of plasmin generation, is regulated by growth factors and
      changes in cell shape. To evaluate the specific relationship between PAI-1 gene
      expression and cytoarchitecture, serum-free cultures of quiescent rat kidney
      (NRK) cells were exposed to cytochalasin D (CD) at concentrations that disrupt
      microfilament structure. Treatment with 1-10 microM CD resulted in an increased
      1) incidence of rounded cells, 2) relative PAI-1 mRNA content, and 3) fraction of
      PAI-1 protein-expressing cells. Abrupt increases in each response were evident at
      a final concentration of 5 microM CD. Maximal levels of induced PAI-1 transcripts
      (18-fold that of control) occurred 4 hours post-CD addition and declined
      thereafter but remained elevated (by at least tenfold) for 24 hours. Assessment
      of the metabolic requirements for CD-induced PAI-1 expression by using the
      protein synthesis inhibitors puromycin and cycloheximide indicated that PAI-1
      transcripts were regulated in a complex manner in response to CD. The predominant
      mode of induction reflected secondary (protein synthesis-dependent) metabolic
      processes, although a minor, albeit significant, primary (protein synthesis
      independent) pathway was also evident. PAI-1 mRNA levels in NRK cells maintained
      in serum- and CD-free agarose suspension culture were low or undetectable.
      Relative abundance of PAI-1 transcripts in suspended cells cultured in the
      presence of CD, however, closely approximated that of plastic-adherent, CD
      treated cells (13-fold over control). NRK cells in suspension culture with or
      without CD were morphologically identical, remaining spherical and unattached. It
      appears, therefore, that cell rounding alone is not a sufficient stimulus to
      induce PAI-1 expression in quiescent NRK cells and that perturbation of the actin
      skeleton as a consequence of CD treatment is a critical event in the inductive
      response. A protein tyrosine kinase is likely involved in the CD-mediated signal
      transduction cascade, since induced PAI-1 expression can be down-regulated by
      genistein and herbimycin A but not by calphostin C or tyrphostin B46.

PMID- 9648917
TI  - Dedifferentiated chondrocytes cultured in alginate beads: restoration of the
      differentiated phenotype and of the metabolic responses to interleukin-1beta.
AB  - Chondrocytes cultivated in monolayer rapidly divide and lose their morphological
      and biochemical characteristics, whereas they maintain their phenotype for long
      periods of time when they are cultivated in alginate beads. Because cartilage has
      a low cellularity and is difficult to obtain in large quantities, the number of
      available cells often becomes a limiting factor in studies of chondrocyte
      biology. Therefore, we explored the possibility of restoring the differentiated
      properties of chondrocytes by cultivating them in alginate beads after two
      multiplication passages in monolayer. This resulted in the reexpression of the
      two main markers of differentiated chondrocytes: Aggrecan and type II collagen
      gene expression was strongly reinduced from day 4 after alginate inclusion and
      paralleled protein expression. However, 2 weeks were necessary for total
      suppression of type I and III collagen synthesis, indicators of a modulated
      phenotype. Interleukin-1beta, a cytokine that is present in the synovial fluid of
      rheumatoid arthritis patients, induces many metabolic changes on the chondrocyte
      biology. Compared with cells in primary culture, the production of nitric oxide
      and 92-kDa gelatinase in response to interleukin-1beta was impaired in cells at
      passage 2 in monolayer but was fully recovered after their culture in alginate
      beads for 2 weeks. This suggests that the effects of interleukin-1beta on
      cartilage depend on the differentiation state of chondrocytes. This makes the
      culture in alginate beads a relevant model for the study of chondrocyte biology
      in the presence of interleukin-1beta and other mediators of cartilage destruction
      in rheumatoid arthritis and osteoarthrosis.

PMID- 9648918
TI  - Characterization of gene-specific DNA repair by primary cultures of rat
      hepatocytes.
AB  - At present, almost all the information on gene-specific DNA repair in mammals
      comes from studies with transformed cell lines and proliferating primary cells
      obtained from rodents and humans. In the present study, we measured the repair of
      specific DNA regions in primary cultures of nondividing rat hepatocytes
      (parenchymal cells). DNA damage was induced by irradiating the primary cultures
      of hepatocytes with ultraviolet (UV) light, and the presence of cyclobutane
      pyrimidine dimers (CPDs) was measured by using T4 endonuclease V in the
      following: a 21-kb BamHI fragment containing the albumin gene, a 14-kb BamHI
      fragment containing the H-ras gene, and the genome overall. The frequency of CPDs
      in the two BamHI fragments and the genome overall were similar and ranged from
      0.5 to 1.3 CPDs per 10 kb for UV doses of 5-30 J/m2. However, the removal of CPDs
      from the DNA fragment containing the albumin gene was significantly higher than
      from that of the genome overall and the DNA fragment containing the H-ras gene.
      Within 24 hr, approximately 67% of the CPDs was removed from the DNA fragment
      containing the albumin gene versus less than 40% for the genome overall and the
      DNA fragment containing the H-ras gene. The lower repair observed for the 14-kb
      fragment containing the H-ras gene is probably indicative of repair of the
      nontranscribed region of this fragment because the H-ras gene makes up only 2.4
      kb of the 14-kb fragment. Primary cultures of hepatocytes removed CPDs from the
      transcribed strand of albumin fragment more efficiently than from the
      nontranscribed strand; however, no differences were observed in the repair of the
      two strands of the fragment containing the H-ras gene. These results demonstrate
      that primary cultures of nondividing rat hepatocytes show differential repair of
      UV-induced DNA damage that is comparable to what has been reported for
      transformed, proliferating mammalian cell lines.

PMID- 9648919
TI  - Retroviral-mediated gene transfer of CSF-1 into op/op stromal cells to correct
      defective in vitro osteoclastogenesis.
AB  - Colony-stimulating factor-1 (CSF-1) released by stromal cells in the bone
      microenvironment is essential for the proliferation of osteoclast progenitors. In
      op/op mutant mice, a thymidine insertion in the coding sequence of the CSF-1 gene
      results in CSF-1 deficiency that in turn leads to decreased osteoclast production
      and osteopetrosis. Because the osteopetrotic defect is due to the failure of
      stromal cells to produce CSF-1, we determined if retroviral-mediated gene
      transfer of the wild-type CSF-1 cDNA into op/op stromal cells would restore their
      ability to support osteoclast formation in vitro. A retroviral vector, L-CSF-1
      SN, was constructed by inserting 1,867 bp of the wild-type CSF-1 cDNA into pLXSN.
      After transduction with L-CSF-1-SN or LXSN constructs, a stable PA31 7 packaging
      cell line that produced a high viral titre was isolated. Viral supernatant from
      this line was used to infect op/op bone marrow stromal cells. Stable L-CSF-1-SN
      op/op stromal clones overexpressed CSF-1 mRNA and released CSF-1 into conditioned
      medium, compared with no CSF-1 released by LXSN op/op stroma. The amount of CSF-1
      produced by two clones was similar to the physiologic level released by normal
      littermate stroma. Southern blot analysis confirmed the presence of intact
      proviral sequences in transduced cells. In coculture assays, L-CSF-1-SN, but not
      LXSN, op/op stromal cells supported the formation of TRAP-positive multinucleated
      cells in the absence of exogenous CSF-1. These findings indicate that genetically
      engineered stromal cells may be used to improve defective osteoclastogenesis and
      suggest that targeting stromal cells to bone is a potentially useful therapeutic
      modality for treating bone disorders.

PMID- 9648920
TI  - Platelet-derived growth factor-induced disruption of gap junctional communication
      and phosphorylation of connexin43 involves protein kinase C and mitogen-activated
      protein kinase.
AB  - Previously we showed a rapid and transient inhibition of gap junctional
      communication (GJC) by platelet-derived growth factor (PDGF) in T51B rat liver
      epithelial cells expressing wild-type platelet-derived growth factor beta
      receptors (PDGFrbeta). This action of PDGF correlated with the
      hyperphosphorylation of the gap junction protein connexin43 (Cx43) and required
      PDGFrbeta tyrosine kinase activity, suggesting the participation of protein
      kinases and phosphatases many of which are activated by PDGF treatment. In the
      present study, two such kinases, namely protein kinase C (PKC) and mitogen
      activated protein kinase (MAPK), are investigated for their possible involvement
      in PDGF-induced closure of junctional channels and Cx43-phosphorylation. Down
      regulation of PKC-isoforms by 12-O-tetradecanoylphorbol-13-acetate or
      pretreatment with the PKC inhibitor calphostin C, completely blocked PDGF action
      on GJC and Cx43. Activation of MAPK correlated with PDGF-induced Cx43
      phosphorylation, and prevention of MAPK activation by PD98059 eliminated the PDGF
      effects. Interestingly, elimination of GJC recovery by cycloheximide was
      associated with a sustained activated-MAPK level. Based on these results we
      postulate that the activation of PKC and MAPK are required in PDGF-mediated Cx43
      phosphorylation and junctional closure.

PMID- 9648921
TI  - Eicosapentaenoic acid attenuates vascular endothelial growth factor-induced
      proliferation via inhibiting Flk-1 receptor expression in bovine carotid artery
      endothelial cells.
AB  - Eicosapentaenoic acid (EPA; 20:5, n-3) can restrain tumor growth and metastasis
      in vivo; however, the mechanism of its antitumor effect is still not fully
      understood. Angiogenesis is a crucial process for tumor growth and metastasis and
      inhibition of tumor angiogenesis can suppress tumor growth and metastasis in
      vivo. Vascular endothelial growth factor (VEGF) is an important angiogenic
      factor. In this study, we investigated the mechanisms of the inhibitory effect of
      EPA on VEGF-induced proliferation of bovine carotid artery endothelial (BAE)
      cells. BAE cells, treated with 0-5 microg/ml EPA for 48 h, displayed a dose
      dependent suppression to VEGF (0.2 nM)-induced proliferation. Similar inhibitory
      effect was not found in BAE cells treated with arachidonic acid (AA; 20:4, n-6),
      or docasahexaenoic acid (DHA; 22:5, n-3). In contrast to its effect on VEGF
      induced proliferation, EPA had no inhibition to basic fibroblast growth factor
      (bFGF, 0.2 nM)-induced proliferation in BAE cells. Both VEGF and bFGF activated
      mitogen-activated protein (MAP) kinase in BAE cells; however, EPA selectively
      inhibited VEGF-induced, but not bFGF-induced activation of MAP kinase. Flk-1
      expression was inhibited dose-dependently in EPA-treated cells, whereas Flt-1
      expression was increased in EPA treated cells. This in vitro inhibitory effect by
      EPA on Flk-1 receptor expression provides indirect evidence that one of the
      mechanisms of EPA for antitumor action in vivo maybe related to its
      antiangiogenic action.

PMID- 9648922
TI  - In vivo overexpression of Core2 N-acetylglucosaminyltransferase prevents
      repopulation of the bone marrow with colony forming cells but fails to affect
      normal T cell development.
AB  - UDP-GlcNAc:Galbet1 --> 3GalNAc-R beta1 --> 6N-acetylglucosaminyltransferase
      (Core2 N-acetyl-glucosaminyltransferase, C2GnT; EC 2.4.1.102) forms beta1 --> 6N
      acetyl-glucosaminyl linkages in O-glycoproteins and creates branches for the
      addition of N-acetyl-lactosamine antennae. Changes in C2GnT activity have been
      associated with immune disorders, malignancies, and T-cell ontogeny. In this
      study, we used SCID (severe combined immune deficiency) mice to determine the
      effects of C2GnT overexpression on hemopoiesis, and in particular, on thymocyte
      development. BALB/c bone marrow cells transfected with C2GnT using the retroviral
      murine stem cell vector were used to repopulate SCID mice. Mice were analysed 3
      weeks to 3 months after bone marrow transfer. Elevated levels of C2GnT activity
      in bone marrow, spleen, and thymus from mice repopulated with C2GnT transfected
      bone marrow cells indicated that C2GnT was overexpressed in recipient mice. In
      C2GnT repopulated mice, up to 50% of T cells showed an increase in CD43 130-kDa
      expression, compared with T cells from control animals, indicative of an elevated
      C2GnT activity in these cells. Furthermore, T-cell subset numbers appeared to be
      normal, suggesting that C2GnT overexpression did not alter T-cell ontogeny.
      Interestingly, C2GnT overexpression negatively affected the repopulation of
      myeloid cells. Only insignificant numbers of interleukin-3/granulocyte-macrophage
      colony stimulating factor (IL-3/GM-CSF) responsive bone marrow cells were found
      to be retrovirally transfected in C2GnT repopulated mice, whereas up to 50% of IL
      3/GM-CSF responsive bone marrow cells were found to be retrovirally transfected
      in corresponding controls. These data indicate that in vivo overexpression of
      C2GnT negatively interferes with the myeloid differentiation pathway but does not
      affect T-cell development.

PMID- 9648923
TI  - Amino acid depletion modulates vascular endothelial growth factor production
      during the life span of human vascular smooth muscle cells.
AB  - The role of nutrient supply in the replicative capacity and secretory phenotype
      of cultured human diploid cells is unclear. We examined the relationship between
      amino acid privation, the secretion of vascular endothelial growth factor (VEGF)
      and growth phenotype of vascular smooth muscle cells (VSMC), and endothelial
      cells. Cultures of VSMCs, but not endothelial cells, were growth inhibited by
      exposure to medium that was 75% deficient in leucine, methionine, arginine, and
      cysteine over two passages. Exposed VSMC cultures exhibited an increased
      vulnerability to apoptosis. The maximal cumulative population doubling of the
      exposed cells was reduced significantly compared with the control cells (25.7 +/-
      2.0 doublings vs. 27.9 +/- 2.1 doublings; P < 0.03). Constitutive VEGF production
      first became evident in the later passages of the exposed and nonexposed cell
      cultures. However, production of VEGF was 17-fold greater in the exposed cultures
      at the tenth passage (P < 0.001). The replicative capacity and constitutive
      production of VEGF in VSMCs in culture may be programmed by transient privation
      of amino acids. These observations are relevant to new concepts concerning the
      pathogenesis of vascular disease.

PMID- 9648924
TI  - Reaction of mast cell proteases tryptase and chymase with protease activated
      receptors (PARs) on keratinocytes and fibroblasts.
AB  - Protease activated receptors (PARs) compose a family of G protein signal
      transduction receptors activated by proteolysis. In this study, the
      susceptibility of PARs expressed on human keratinocytes and dermal fibroblasts to
      the human mast cell proteases tryptase and chymase was evaluated. PAR activation
      was measured by monitoring cytosolic [Ca2+] in cells loaded with the fluorescent
      Ca2+ probe Fura-2. Tryptase produced transient cytosolic Ca2+ mobilization in
      keratinocytes, but not in fibroblasts. Ca2+ mobilization in keratinocytes
      required enzymatically active tryptase, demonstrated desensitization, and was
      blocked by pretreatment of cells with the PAR-2 peptide agonist SLIGKV, trypsin,
      or the phospholipase inhibitor U73122. Heparin, a GAG that binds to tryptase,
      stabilizing its functional form, also inhibited tryptase-induced Ca2+
      mobilization. The maximal response elicited by tryptase was smaller than that
      observed upon treatment of keratinocytes with trypsin, a known activator of PAR
      2, and keratinocytes made refractory to tryptase by pretreatment with the
      protease remained responsive to trypsin. Pretreatment of keratinocytes with
      thrombin, an activator of PAR-1 and -3 (thrombin receptors), had no detectable
      effect on the tryptase or trypsin responses. These data suggest that in
      keratinocytes tryptase may be activating a subpopulation of PAR-2 receptors.
      Treatment of keratinocytes or fibroblasts with human chymase did not produce Ca2+
      mobilization, nor did it affect Ca2+ mobilization produced by trypsin. However,
      chymase pretreatment of fibroblasts rapidly inhibited the ability of these cells
      to respond to thrombin. Inhibition was dependent on chymase enzymatic activity
      and was not significantly affected by the presence of heparin. This finding is
      consistent with studies indicating that PAR-1 may be susceptible to proteases
      with chymotrypsin-like specificity. These results suggest that the proteases
      tryptase and chymase secreted from mast cells in skin may affect the behavior of
      surrounding cells by the hydrolysis of PARs expressed by these cells.

PMID- 9648925
TI  - Stretch-induced membrane type matrix metalloproteinase and tissue plasminogen
      activator in cardiac fibroblast cells.
AB  - In the normal heart, cardiomyocytes are surrounded by extracellular matrix (ECM)
      and latent matrix metalloproteinases (MMPs), which are produced primarily by
      cardiac fibroblasts. An activator of latent MMPs might be induced by ischemic
      conditions or pressure-induced stretching. To test the hypothesis that an
      activator of latent MMP is induced in the ischemic heart during transformation of
      a compensatory hypertrophic response to a decompensatory failing response in
      cardiac fibroblast cells, we stretched the human cardiac fibroblasts at 25
      cycles/min in serum-free or 5% serum culture condition. The membrane type (MT)
      MMP activity in stretched cells was measured by zymography and immuno-blot
      analyses using MT-MMP-2 antibody. The MT-MMP activity was further characterized
      by transverse-urea gradient (TUG)-zymography. The results suggested that stretch
      induced a membrane MMP in the fibroblasts that was similar to the MT-MMP induced
      in ischemic heart. Furthermore, we observed that membrane MMP has distinct
      mobility in TUG-zymography. To localize the MT-MMP and tissue plasminogen
      activator (tPA) of latent MMPs, the membrane and cytosol were separated by a
      method employing a detergent and sedimentation. The MT-MMP and tPA activities of
      cytosol and membrane fractions were measured by gelatin- and plasminogen
      zymography, respectively. Differential-display mRNA analysis was performed on
      control and stretched cells. In situ immuno-labelling was performed to localize
      the MT-MMP. The results indicate that induction of MT-MMP occurred in the
      membrane fractions. The secretion of tPA was elevated in the stretched cells. The
      MT-MMP activity was inhibited by prior incubation with an antibody generated to
      membrane MMP. The tPA activity was inhibited by using tPA antibody. These results
      suggest that, under stretched conditions, neutral transmembrane matrix
      proteinases are induced in the cardiac fibroblasts. This may lead to activation
      of adverse ECM remodeling, cardiac dilatation, and failure.

PMID- 9648926
TI  - Heregulin-dependent autocrine loop regulates growth of K-ras but not erbB-2
      transformed rat thyroid epithelial cells.
AB  - The EGF-like family of proteins, such as epidermal growth factor (EGF),
      transforming growth factor alpha (TGFalpha), amphiregulin (AR), betacellulin
      (BTC), cripto-1 (CR-1), and heregulin (HRG), plays an important role in the
      pathogenesis of several human carcinomas as autocrine growth factors.
      Differentiation and proliferation of rat thyroid cells in culture (FRTL-5 cells)
      are regulated by thyrotropin (TSH); withdrawal of TSH from culture medium
      produces growth arrest, whereas its addition to quiescent cells stimulates cell
      entry into S phase. Instead, transformed thyroid cell lines as FRTL-5H2 cell
      line, overexpressing erbB-2, Kimol cells, transformed by the wild-type K-ras and
      A6 clone, transformed by a temperature sensitive K-ras mutant, can grow without
      addition of TSH to the culture medium. In order to identify whether EGF-like
      growth factors and corresponding receptors (erbB-2, erbB-3, and erbB-4) could be
      involved in the autonomous growth of these transformed rat thyroid epithelial
      cells, Northern blot for mRNA analysis and Western blot for protein expression
      were performed. In contrast to normal control FRTL-5 cells, both K-ras and erbB-2
      transformed cells expressed elevated levels of erbB-2 receptor. Moreover, both K
      ras transformed cells, Kimol and A6 cells, but no FRTL-5H2 cells, were found able
      to express also high levels of erbB-4 receptor and HRG/NDF ligand. Treatment of K
      ras transformed thyroid cells with neutralizing antibody against HRG/NDF reduced
      by 50% cell proliferation. These data indicate that unlike the erbB-2
      overexpressing FRTL-5 cells, in K-ras rat thyroid epithelial cells, the growth
      factor heregulin signals through the heterodimer erbB-2/erbB-4 receptors in an
      autocrine fashion.

PMID- 9648927
TI  - Multivalent cations and ligand affinity of the type 1 insulin-like growth factor
      receptor on P2A2-LISN muscle cells.
AB  - Mouse P2A2-LISN myoblasts are transfected cells that overexpress the human type 1
      insulin-like growth factor (IGF) receptor. Because the type 1 IGF receptor is the
      major binding site for both IGF-I and IGF-II, this cell line is an excellent
      model to determine the effect of multivalent cations on ligand binding
      specifically to this type of receptor. Competitive binding assays were performed
      to characterize IGF binding and Scatchard analysis to quantify affinity (Ka).
      125I-IGF-I, 125I-IGF-II, and 125I-R3-IGF-I bind only to the type 1 IGF receptor
      on these cells. Zn2+ increased binding of the three ligands to the type 1 IGF
      receptor by 17 to 35%. Cd2+ significantly increased binding of 125I-IGF-I,
      although by only 8%. La3+ and Cr3+ did not effect binding. Au3+ decreased IGF
      binding by approximately 56%. Scatchard analysis produced nonlinear concave-down
      plots yielding binding constants for high and low affinity sites. Zn2+ increased
      the strength of only the high affinity sites. Au3+ decreased the affinity of both
      high and low affinity sites. Zn2+ increased binding with a half-maximal effect
      between 40 microM and 60 microM. Half-maximal dose of Au3+ was >130 microM. Zinc,
      gold, and cadmium bind to similar regions within proteins (a zinc-binding motif)
      and only these cations were found to affect receptor binding indicating similar
      mechanisms of action. Thus, multivalent cations may alter IGF binding to cell
      surface receptors ultimately controlling growth. Physiologically this may be
      especially important for the growth promoting effects of Zn2+.

PMID- 9648928
TI  - Overexpression of protein kinase C alpha enhances lipopolysaccharide-induced
      nitric oxide formation in vascular smooth muscle cells.
AB  - Our previous studies showed that lipopolysaccharide (LPS)-induced nitric oxide
      (NO) synthesis in cardiovascular tissues is attenuated by protein kinase C (PKC)
      inhibitors. In the current study, we identify a specific PKC isotype involved in
      the LPS signal transduction pathway that leads to NO formation in rat vascular
      smooth muscle cells (VSMC). VSMC were transfected with a mammalian expression
      vector containing a full length PKCalpha cDNA insert, and a stable transfectant
      overexpressing PKCalpha was obtained as evidenced by increased expression of
      PKCalpha mRNA and protein. In response to 100 ng/ml LPS stimulation, the PKCalpha
      transfectants showed a 1.8-fold increase in PKC activity at 30 min and a twofold
      increase in NO production over 24 hr compared with cells transfected with control
      plasmids. The LPS-stimulated increase in NO synthesis in PKCalpha transfectants
      was blocked by the specific PKCalpha inhibitor Go 6976. After 6 hr LPS treatment,
      PKCalpha-transfected and control cells showed equivalent increases in mRNA and
      protein for the inducible NO synthase. NO synthase activity of the cell extracts
      assayed in the presence of excess substrate and cofactors was not significantly
      different between PKCalpha-transfected and control cells after LPS stimulation.
      However, mRNA levels for GTP cyclohydrolase I, a key enzyme in (6R)-tetrahydro-L
      biopterin synthesis, and cationic amino acid transporter-2, involved in L
      arginine transport, was enhanced in cells overexpressing PKCalpha compared with
      control cells. These results suggest that PKCalpha plays an important role in LPS
      induced NO formation and that a significant portion of this effect may be by
      means of enhanced substrate availability to the inducible nitric oxide synthase
      enzyme.

PMID- 9648929
TI  - Different signaling pathway between sphingosine-1-phosphate and lysophosphatidic
      acid in Xenopus oocytes: functional coupling of the sphingosine-1-phosphate
      receptor to PLC-xbeta in Xenopus oocytes.
AB  - In Xenopus oocytes, both sphingosine-1-phosphate (S1P) and lysophosphatidic acid
      (LPA) activate Ca2+-dependent oscillatory Cl- currents by acting through membrane
      bound receptors. External application of 50 microM S1P elicited a long-lasting
      oscillatory current that continued over 30 min from the beginning of oscillation,
      with 300 nA (n = 11) as a usual maximum peak of current, whereas 1-microM LPA
      treatment showed only transiently oscillating but more vigorous current
      responses, with 2,800 nA (n = 18) as a maximum peak amplitude. Both phospholipid
      induced Ca2+-dependent Cl- currents were observed in the absence of extracellular
      Ca2+, were blocked by intracellular injection of the Ca2+ chelator, EGTA, and
      could not be elicited by treatment with thapsigargin, an inhibitor of endoplasmic
      reticulum (ER) Ca2+ ATPase. Intracellular Ca2+ release appeared to be from
      inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+ store, because Cl- currents
      were blocked by heparin injection. Pretreatment with the aminosteroid, U-73122,
      an inhibitor of G protein-mediated phospholipase C (PLC) activation, to oocytes
      inhibited the current responses evoked both by S1P and LPA. However, when they
      were injected with 10 ng of antisense oligonucleotide (AS-ODN) against Xenopus
      phospholipase C (PLC-xbeta), oocytes could not respond to S1P application,
      whereas they responded normally to LPA, indicating that the S1P signaling pathway
      goes through PLC-xbeta, whereas LPA signaling goes through another unknown PLC.
      To determine the types of G proteins involved, we introduced AS-ODNs against four
      types of G-protein alpha subunits that were identified in Xenopus laevis;
      G(q)alpha, G11alpha, G0alpha, and G(i1)alpha. Among AS-ODNs against the G alphas
      tested, AS-G(q)alpha and AS-G(i1)alpha to S1P and AS-G(q)alpha and AS-G11alpha to
      LPA specifically reduced current responses, respectively, to about 20-30% of
      controls. These results demonstrate that LPA and S1P, although they have similar
      structural features, release intracellular Ca2+ from the IP3-sensitive pool, use
      different components in their signal transduction pathways in Xenopus oocytes.

PMID- 9648930
TI  - Expression of transforming growth factor-beta receptor type II and tumorigenicity
      in human breast adenocarcinoma MCF-7 cells.
AB  - To analyze transforming growth factor-beta (TGF-beta) response during MCF-7 cell
      progression, early passage (MCF-7E, < 200 passage) and late passage (MCF-7L, >
      500 passage) cells were compared. MCF-7E cells showed an IC50 of approximately 10
      ng/ml of TGF-beta1, whereas MCF-7L cells were insensitive. MCF-7E cells contained
      approximately threefold higher levels of TGF-beta receptor type II (TbetaRII)
      mRNA than MCF-7L, but their TbetaRI levels were similar. MCF-7E parental cells
      showed higher TbetaRII promoter activity than MCF-7L cells, which could be
      attributed to changes in Sp1 nuclear protein levels. Receptor cross-linking
      studies indicated that the cell surface receptor levels parallel mRNA levels in
      both cell lines. Limiting dilution clones of MCF-7E cells were established to
      determine the heterogeneity of TbetaRII expression in this cell line, and they
      showed varying degrees of TbetaRII expression. Fibronectin was induced at higher
      levels in cells expressing higher TbetaRII levels. All three TGF-beta isoforms
      were detected in limiting dilution clones and parental cells, but TGF-beta1 was
      more abundant relative to TGF-beta2 or 3, and no correlation between TGF-beta
      isoform profile with TGF-beta sensitivity was found. MCF-7L cells were
      tumorigenic and formed xenografts rapidly and progressively, whereas MCF-7E
      parental and limiting dilution clonal cells showed transient tumor formation
      followed by regression. These results indicate that decreased TbetaRII
      transcription in breast cancer cells leads to a loss of TbetaRII expression,
      resulting in cellular resistance to TGF-beta which contributes to escape from
      negative growth regulation and tumor progression.

PMID- 9648931
TI  - 17beta-estradiol regulation of protein kinase C activity in chondrocytes is sex
      dependent and involves nongenomic mechanisms.
AB  - 17Beta-estradiol (E2) regulates growth plate chondrocyte differentiation in both
      a sex- and cell maturation-dependent manner, and the sex-specific effects of E2
      appear to be mediated in part by membrane events. In this study, we examined
      whether E2 regulates protein kinase C (PKC) in a cell-maturation and sex-specific
      manner and whether E2 uses a nongenomic mechanism in regulating this enzyme. In
      addition, we determined if PKC mediates the E2-dependent stimulation of alkaline
      phosphatase activity seen in chondrocytes. Confluent, fourth passage resting zone
      (RC) and growth zone (GC) chondrocytes from male and female rat costochondral
      cartilage were treated with 10(-10) to 10(-7) M E2. E2 caused a dose-dependent
      increase in PKC in RC and GC cells from female rats. Peak stimulation was at 90
      min. Increased PKC was evident by 3 min in both RC and GC and was still evident
      in RC cells at 720 min, but in GC cells activity returned to baseline by 270 min.
      Actinomycin D had no effect at 9, 90, 270, or 720 min, but there was a small
      decrease in E2-stimulated PKC in RC treated with cycloheximide at 90 and 270 min
      and in GC treated for 90 min. E2 increased cytosolic and membrane PKC at 9 min
      and by 90 min promoted translocation of PKC activity from the cytosol to the
      membranous compartment of female RC cells. Antibodies specific for the alpha,
      beta, delta, epsilon, and zeta isoforms of PKC revealed that PKCalpha in female
      GC and RC cells is activated by E2. There was a small, but statistically
      significant, increase in PKC in male RC cells in response to E2, but it was not
      dose-dependent, and no effect of E2 was noted in male GC cells. 17Alpha
      estradiol, an inactive isomer of E2, did not affect PKC specific activity in RC
      or GC cells from either female or male rats. Chelerythrine, a specific inhibitor
      of PKC, inhibited E2-dependent alkaline phosphatase activity, indicating that E2
      mediates its rapid effects on alkaline phosphatase via PKC.

PMID- 9648932
TI  - Hypothesis: ligand/receptor-assisted nuclear translocation of STATs.
AB  - The STAT transcription factors are mediators of signal transduction of a variety
      of factors, including interferons (IFNs), interleukins, growth factors, and
      peptide hormones. Subsequent to activation, STATs are translocated to the nucleus
      apparently through the well-described importin/Ran system, where they activate
      target genes. Molecules utilizing this nuclear import system require specific
      nuclear localization sequences (NLSs). Paradoxically, such NLSs are not
      identifiable on STATs, thus raising the question of how they are imported into
      the nucleus. Of considerable interest is the observation that ligands and/or
      receptors that signal through STATs contain putative NLSs and, where examined,
      either ligand or receptor undergoes nuclear translocation. We hypothesize that
      ligands and/or their receptors serve as vehicles for the nuclear translocation of
      STATs, and that they may be directly involved in signal transduction. Using
      IFNgamma as a model system, we provide a possible mechanism for how this direct
      role is fulfilled. A functional NLS has been identified in a C-terminal domain of
      IFNgamma. This domain and the NLS contained within are crucial for the biological
      properties of IFNgamma in that a peptide encompassing this domain is sufficient
      to induce an antiviral state. Further, this domain binds specifically to a
      membrane-proximal region internal cytoplasmic domain of the alpha subunit of the
      receptor complex in a region that is directly involved in the recruitment and
      activation of the JAK/STAT pathway. We suggest that this novel mode of receptor
      recognition and activation may be a driving force for nuclear translocation of
      molecules like STATs that are associated with the ligand-receptor complex.

PMID- 9648933
TI  - Endogenous sodium pump inhibitors and blood pressure regulation: an update on
      recent progress.
AB  - Rapid progress has occurred recently in understanding the origin, chemistry,
      synthesis, control, and actions of endogenous materials that may be ligands for
      the cardiac glycoside binding site on the mammalian sodium pump (Na,K-ATPase).
      The present paper reviews this progress and examines in detail the evidence
      supporting ouabain-like and bufodienolide-like compounds as functioning in
      endogenous control of sodium pump activity, renal sodium excretion, blood
      pressure, and cardiovascular contractility. Other novel compounds identified in
      this search as potentially influencing natriuresis and blood pressure are also
      discussed.

PMID- 9648934
TI  - Pathophysiological effects of nicotine on the pancreas.

PMID- 9648935
TI  - The actions of exogenous dehydroepiandrosterone in experimental animals and
      humans.
AB  - Dehydroepiandrosterone (DHEA) is the major adrenal steroid of young adults;
      however, its physiologic functions, if any, are not known. The purpose of this
      review is to evaluate the current literature in which DHEA was administered to
      either humans or experimental animals to discern what these functions might be.
      Reports are divided into five areas: neurologic, immunologic, cardiovascular,
      oncologic, and metabolic. Particular attention is paid to the dosage and route of
      administration. This type of analysis shows that at the lowest doses, DHEA has
      effects on neurologic and immunologic tissues, suggesting that these two sites
      may be physiologic targets. DHEA also affects cardiologic and metabolic functions
      as well as tumor growth, but such actions require higher doses and may reflect
      'pharmacologic' activities. It is proposed that DHEA's pattern of activity
      represents a new class of steroid hormones, the "Regnantoids." Further progress
      in the endocrinology of this family of steroids may only come when synthetic,
      long-acting analogs of DHEA are available for in vitro studies to allow
      correlations between hormone action and receptor binding.

PMID- 9648936
TI  - Ion channels in vascular smooth muscle: alterations in essential hypertension.
AB  - Essential hypertension is characterized by a near normal cardiac output but an
      increase in total peripheral resistance. In turn, total peripheral resistance is
      controlled directly by the diameter of the small arteries and arterioles like
      those in the kidney. The dynamic regulation of renal vessel diameter is governed
      by the contractile state of the vascular smooth muscle cells that line the vessel
      walls. This review addresses the role of a number of different ion channels to
      initiate and maintain the contractile state of the vascular smooth muscle cells
      in hypertension and the potential prevention of hypertension through gene
      therapy. These specific channels include Ca2+, K(Ca), Kv, and Cl- channels. In
      hypertension, it has been reported that increased activity of Ca2+ channels and
      decreased activity of Kv channels are responsible for the increased contractile
      tone and resting membrane potential observed in dissociated vascular smooth
      muscle cells from the spontaneously hypertensive rat. In contrast, increased
      activity of K(Ca) channels in vascular smooth muscle cells of the SHR has been
      hypothesized to dampen or brake the activity of Ca2+ and Kv channels. Finally,
      recent evidence suggests that introducing angiotensin II type-1 receptor
      antisense into prehypertensive rat pups prevents the onset of pathophysiological
      alterations observed in hypertension including K+ channel alterations. These
      results suggest that gene therapy may be a useful pharmacological and
      physiological tool to combat hypertension.

PMID- 9648937
TI  - Attenuation of gonadotropin-releasing hormone reflex to coitus by alpha1
      adrenergic receptor blockade in the rabbit.
AB  - The coitally induced gonadotropin-releasing hormone (GnRH)/luteinizing hormone
      (LH) surge in the rabbit is preceded by an enhanced secretion of hypothalamic
      norepinephrine (NE). To investigate if adrenergic receptors are essential for the
      GnRH/LH surge, we administered a specific alpha1 receptor blocker, prazosin, into
      either the arcuate nucleus-median eminence (AME) or the third cerebroventricle
      (3rd V) of tethered, freely moving intact female rabbits via push-pull perfusion
      (PPP). Dual cannulae for PPP and drug infusion were placed stereotaxically either
      into the AME or AME and 3rd V of each rabbit after insertion of a permanent
      femoral venous catheter for serial blood sampling. During an experiment,
      continuous PPP samples and 10-min intermittent blood samples were collected for 5
      6 hr. Females received either prazosin or control medium (artificial
      cerebrospinal fluid into an AME or saline into a 3rd V cannula) for 4 hr,
      beginning 1 hr before coitus. Intraventricular infusion of prazosin significantly
      (P < 0.05) suppressed both the postcoital GnRH and the LH surges. Administration
      of prazosin into the AME also attenuated the magnitude of the postcoital GnRH
      surge (P < 0.05) whereas postcoital LH values were not decreased below that of
      the control group (P > 0.05). The results suggest that alpha1 receptors are
      physiologically active in the initiation of the postcoital GnRH release. These
      findings, along with our earlier report of enhanced postcoital NE secretion,
      reinforce the hypothesis that NE plays an essential role in the preovulatory
      GnRH/LH surge in rabbits.

PMID- 9648938
TI  - Dehydroepiandrosterone (DHEA) sulfate prevents reduction in tissue vitamin E and
      increased lipid peroxidation due to murine retrovirus infection of aged mice.
AB  - Dietary effects of dehydroepiandrosterone sulfate (DHEAS) supplementation on
      tissue antioxidants and lipids were investigated in retrovirus infected mice.
      DHEA is a powerful antioxidant and immunomodulator whose production declines with
      age. For this study, twenty-four female, 15-month-old C57BL/6 mice were left
      uninfected while twenty-four were infected with LP-BM5 murine leukemia virus,
      causing murine AIDS. The retroviral infection caused immune dysfunction and loss
      of hepatic and cardiac vitamins E and A, resulting in increased lipid peroxides.
      Treatment with DHEAS at 0.01 or 0.005% in drinking water for 10 weeks post
      infection significantly (P < 0.05) lowered lipid peroxidation in both heart and
      liver tissues. Treatment with DHEAS also largely prevented loss of the
      antioxidants, such as vitamin E and A, and prevented loss of phospholipid in the
      hearts and livers of the old uninfected as well as infected mice. This study
      suggests that DHEAS supplementation reduces damage associated with elevated
      oxidation due to aging and retrovirus infection.

PMID- 9648939
TI  - Calorie restriction delays the crescentic glomerulonephritis of SCG/Kj mice.
AB  - Reduced dietary calories can delay the onset and diminish the severity of murine
      autoimmunities of numerous inbred and hybrid mutant strains. We sought to
      determine whether the precipitous, autoimmune, crescentic glomerulonephritis of
      recombinant inbred SCG/Kj mice could be abrogated similarly by calorie
      restriction. Weanling SCG/Kj mice develop hematuria and proteinuria, and 50% die
      as 16-week-old young adults. In this study, 113 4-week-old SCG/Kj mice were fed
      either ad libitum a milled chow (Group A, n = 50), or a semipurified diet (Group
      B, n = 29), or were fed a calorie-restricted semipurified diet (Group C, n = 34),
      so that mice of Group C consumed approximately 32% fewer calories, but similar
      amounts of essential dietary constituents as those of Group B. Calorie
      restriction of Group C provided modest (P = 0.05) or substantial survival
      advantage (P = 0.001) compared to the ad libitum feeding of Groups B or A,
      respectively. Progression to severe glomerular pathology was delayed among Group
      C mice, with more than a 5-week delay to heavy proteinuria (>100 mg/dl), a >4
      week delay to hematuria, and a >5-week delay to median mortality, representing a
      20% or 25% extension of median life span, compared to ad libitum-fed Group B and
      A mice, respectively. Mean glomerular histopathology scores were also lower in
      calorie-restricted mice compared to the ad libitum-fed cohorts (P = 0.001).
      Titers of anti-ss-DNA, ds-DNA, and ANCA autoantibodies developed in weanlings
      prior to the full imposition of calorie restriction and were not reduced
      significantly by calorie restriction.

PMID- 9648940
TI  - Prevention of crescentic glomerulonephritis in SCG/Kj mice by bone marrow
      transplantation.
AB  - Transplantation of MHC-compatible, T-cell-depleted, bone marrow cells has
      successfully treated autoimmunities, immunodeficiencies, malignancies, and
      developmental deficiencies of the hematopoietic system. Recombinant inbred SCG/Kj
      mice develop spontaneous crescentic glomerulonephritis, systemic vasculitis, and
      a lymphoproliferative disorder early in life. To determine whether the
      precipitous autoimmune disease of SCG/Kj mice could be treated by bone marrow
      transplantation, 30 SCG/Kj mice were engrafted with T-cell-depleted, bone marrow
      (TCDM) from allogeneic, MHC-compatible, autoimmune-resistant C3H/He donors, and
      30 SCG/Kj mice served as controls and received TCDM from syngeneic, SCG/Kj
      donors. A significant survival advantage was evident from SCG/Kj mice engrafted
      with C3H/He TCDM (p < 0.005), and an 89% extension of median survival compared to
      recipients of SCG/Kj TCDM. Within 28 weeks post-transplantation, 62% of mice
      engrafted with SCG/Kj TCDM had died with clinical signs of fatal crescentic
      glomerulonephritis. This result compared with only 10% of mice engrafted with
      C3H/He TCDM. Mice engrafted with SCG/Kj TCDM developed significantly greater
      titers of autoantibodies to ss-DNA, ds-DNA, and myeloperoxidase (ANCA) (p <
      0.001), had shorter latencies to the development of, and a greater incidence of
      proteinuria, hematuria, and peripheral lymphadenopathy, and a greater mean grade
      of glomerular lesion (p < 0.001), than mice engrafted with C3H/He TCDM. These
      findings indicate that the genetic defect of the SCG/Kj strain of mice resides
      within the hematopoietic stem cells and provokes the speculation that bone marrow
      transplantation might be a useful means of treating progressive crescentic
      glomerulonephritis in humans.

PMID- 9648941
TI  - Circadian variation of urinary excretion of elastin and collagen crosslinks.
AB  - Urinary levels of collagen- and elastin-crosslink amino acids have been used as
      biologic markers for degradation of collagen and elastin in the body. Circadian
      variation of collagen-crosslink amino acids is well known. The current study was
      undertaken to determine whether there is also circadian variation in excretion of
      elastin-crosslink amino acids. We used an isotope dilution-HPLC assay to measure
      the elastin-crosslink amino acids, desmosine (DES) and isodesmosine (IDES), and
      the collagen-crosslink amino acids, hydroxylysyl pyridinoline (HP) and lysyl
      pyridinoline (LP), in urine. Sixteen apparently healthy subjects collected urine
      from 5:00 to 7:00 AM, and from 5:00 to 7:00 PM. Mean urinary excretion of DES and
      IDES in women was 56% and 41% higher (P < 0.001), respectively, in AM versus PM
      specimens when normalized by the creatinine content of the urine specimen. For
      men, the corresponding values were 11% and 13% higher (not statistically
      significant). Mean urinary excretion of HP and LP in women was 61% and 71% higher
      (P < 0.001), respectively, in AM versus PM specimens. For men, the corresponding
      values were 11% and 19% higher (not statistically significant). Differences were
      not found in the AM versus PM rates of excretion of creatinine in men or women.
      These findings demonstrate the occurrence of circadian variation in HP, LP, DES
      and IDES in women but not in men. We conclude that the time of collection of
      urine specimens, especially from women, must be taken into consideration in using
      the urinary levels of these crosslink amino acids as biologic markers for
      collagen or elastin degradation.

PMID- 9648942
TI  - Effects of dietary gamma-linolenic acid on blood pressure and adrenal angiotensin
      receptors in hypertensive rats.
AB  - In a previous study, we showed that dietary gamma-linolenic acid (GLA), an omega
      6 polyunsaturated fatty acid found in borage oil (BOR), attenuates the
      development of hypertension in young spontaneously hypertensive rats (SHR). The
      purpose of this study was to determine the effects of dietary GLA on established
      hypertension in adult rats, as well as its effects on components of the renin
      angiotensin-aldosterone axis. For 5 weeks, male SHR (14-15 weeks old) were fed a
      basal fat-free diet to which 11% by weight of sesame oil (SES) or BOR was added.
      Systolic blood pressure (SBP), determined by the tail cuff method, and weight
      were measured weekly. Plasma renin activity (PRA), aldosterone (PA), and
      corticosterone (PC) levels were measured at the end of the dietary treatments.
      The adrenal glands were homogenized, and angiotensin II (ANG II) binding was
      measured and plotted according to Scatchard. Systolic blood pressure was 12 mmHg
      lower at Week 5 in SHR fed the BOR diet compared to SES-fed rats (P < 0.005).
      Weight gains were similar in both dietary groups. Plasma aldosterone was lower,
      PRA was higher, and the PA/PRA ratio was significantly lower (P < 0.05) in BOR
      fed rats. Levels of PC were the same in both groups. The BOR-enriched diet
      reduced adrenal ANG II receptor density and affinity compared to the SES diet.
      Results suggest that BOR inhibits adrenal responsiveness to ANG II by an action
      on adrenal receptors. Our findings demonstrated that dietary GLA lowers SBP in
      adult SHR. This effect may be mediated, at least in part, by interference with
      the renin-angiotensin-aldosterone system at the level of adrenal ANG II
      receptors.

PMID- 9648943
TI  - Inhibition of gingival collagenase gene expression by dexamethasone.
AB  - Glucocorticoids are potent immunosuppressants shown to be effective in the
      treatment of inflammatory diseases. Reportedly, they work, in part, by inhibiting
      cytokines and other transcription factors including AP-1. In this study we
      investigated the mechanisms of efficient repression of collagenase gene
      expression by dexamethasone in the human gingival fibroblast. Northern analyses
      showed that IL-1-dependent collagenase mRNA production was significantly
      decreased in the presence of dexamethasone. The influence of dexamethasone on the
      transcription factor NF-kappaB, STAT3, and AP-1 was investigated by using the gel
      mobility shift assay with nuclear extracts prepared from the cells grown in the
      presence of dexamethasone. We observed that in addition to AP-1, binding of NF
      kappaB and STAT3 to DNA was also decreased significantly. Additionally,
      dexamethasone induced the transcription of the I kappaB-alpha gene suggesting
      that in the presence of dexamethasone, NF-kappaB quickly reassociates with newly
      synthesized I kappaB-alpha and markedly reduces the amount of NF-kappaB. CAT
      transfection studies utilizing collagenase promoter demonstrated a dose-dependent
      transcriptional inhibition of IL-1-induced gingival collagenase gene expression
      by dexamethasone. These data reveal that collagenase gene expression can be
      regulated by the impairment of IL-1-stimulated NF-kappaB, STAT3, and AP-1
      activities, and can highlight a possible molecular mechanism for the anti
      inflammatory effects of glucocorticoids.

PMID- 9648944
TI  - Insulin-like growth factor-I and high protein diet decrease calpain-mediated
      proteolysis in murine muscular dystrophy.
AB  - In muscular dystrophy (MD) the imbalance between muscle protein synthesis and
      degradation may be an important factor leading to muscle wasting. The three major
      pathways of muscle proteolysis identified in skeletal muscle are: the lysosomal
      cathepsin pathway, the calcium-dependent calpain pathway, and the ATP-dependent
      ubiquitin pathway. Insulin-like growth factor I (IGF-I) and a high-protein diet
      (HPD) have been shown to reduce proteolysis in skeletal muscle. We examined the
      effect of 6 weeks of recombinant human IGF-I (rhIGF-I) alone or in combination
      with HPD treatment on the proteolytic pathways in skeletal muscle of 129 ReJ
      dystrophic (dy) mice. (A group of normal (Norm) nondystrophic (129 J) mice were
      included as controls). Untreated dy mice exhibited increased net proteolysis (P <
      0.05), elevated net calpain activity (P < 0.01), and increased ubiquitin levels
      when compared to control mice (P < 0.05). Our evidence suggests that HPD and
      rhIGF-I decrease proteolysis in the 129 ReJ dy mouse. This effect appears
      attributable, at least in part, to reduced calpain-mediated myofibrillar
      breakdown (P < 0.05) due to decreased calpain autolysis or increased calpastatin
      levels. In contrast to calpain, cathepsin B activity was increased in HPD and
      rhIGF-I + HPD-treated dy muscle (P < 0.05) and unaltered in the rhIGF-I treated
      animals. Levels of free and protein-conjugated ubiquitin were also increased in
      rhIGF-I, and rhIGF-I + HPD treated dyanimals (P < 0.05). The amelioration of
      muscle wasting in the 129 ReJ dy model by HPD and/or rhIGF-I may have potential
      implications in the treatment of human MD.

PMID- 9648945
TI  - Eosinophil priming and migration in idiopathic pulmonary fibrosis.

PMID- 9648946
TI  - From clot to collagen: coagulation peptides in interstitial lung disease.

PMID- 9648947
TI  - Chlorofluorocarbon-free inhalers: are we ready for the change?
AB  - Chlorofluorocarbons (CFCs) damage stratospheric ozone permitting enhanced levels
      of ultraviolet B radiation to reach the Earth's surface. As a result, production
      of CFCs is now banned under the Montreal Protocol with the exception of their
      temporary continued use in pressurized metered dose inhalers used to treat those
      with airway disorders. Replacement propellants have now been identified and shown
      to be safe and a major exercise is under way to reformulate the commonly used
      aerosolized medicines with the new propellants. The new products are now
      undergoing clinical trials and the first reformulated beta-agonist and
      corticosteroid inhalers have reached the marketplace. The majority of the current
      products will have been changed over to the new types over the next 3 yrs, and
      each country will adapt a transition strategy to oversee this process. The
      politicians, the environmentalists, the pharmaceutical industry and the
      regulatory authorities have fulfilled their part in this changeover, and
      respiratory interested health professionals now need to address what this means
      for them and their patients so that there may be a seamless transition for the
      millions of people who use inhaled medicines worldwide.

PMID- 9648948
TI  - Eosinophil chemotactic activity in bronchoalveolar lavage from idiopathic
      pulmonary fibrosis is dependent on cytokine priming of eosinophils.
AB  - Increased numbers of eosinophils have been found in bronchoalveolar lavage (BAL)
      fluid obtained from patients with idiopathic pulmonary fibrosis (IPF). This
      suggests the presence of one or more cytokines in the lung tissue of patients
      with IPF, which are involved in the induction of migration of eosinophils towards
      the pulmonary compartment. To evaluate this hypothesis, we studied migratory
      responses of blood eosinophils towards BAL fluid. Migratory responses were tested
      by means of a modified Boyden chamber assay in 21 patients with IPF and 14
      healthy controls. Experiments were performed with unprimed eosinophils and in
      vitro primed eosinophils (preincubated with 10(-11) M granulocyte macrophage
      colony-stimulating factor). Changes in intracellular free Ca2+ ([Ca2+]i) in
      eosinophils in response to BAL fluid were also investigated, to characterize
      putative chemotaxins further. Chemotactic responses of eosinophils were observed
      towards BAL fluid from both patients with IPF and controls, provided that the
      eosinophils were primed. No changes in [Ca2+]i in eosinophils were detected in
      response to BAL fluid. Furthermore, neither a blocking antibody against
      interleukin-8 nor one against regulated on activation, normal T-cell, expressed
      and secreted (RANTES) influenced the response. Since a chemotactic response of in
      vitro primed eosinophils was also observed towards bronchoalveolar lavage fluid
      from normals, it was concluded, that in idiopathic pulmonary fibrosis, apart from
      the presence of a chemotactic factor in the lung tissue, other mechanisms such as
      priming of eosinophils in the peripheral blood are responsible for the
      extravasation of eosinophils into the pulmonary compartment. As no changes in
      [Ca2+]i were observed in the eosinophils after incubation with bronchoalveolar
      lavage fluid, the chemotaxin responsible for the migratory responses is probably
      not one of the known eosinophil-activating chemokines.

PMID- 9648949
TI  - Ionized calcium and 1,25-dihydroxyvitamin D concentration in serum of patients
      with sarcoidosis.
AB  - The aim of this study was to evaluate alterations in calcium metabolism in
      sarcoidosis. The serum concentrations of calcium (sCa), ionized calcium (sCa2+),
      1,25-dihydroxyvitamin D (s1,25(OH)2D3) and parathyroid hormone (sPTH), serum
      angiotensin-converting enzyme activity (sACE) and urinary excretion of calcium
      (uCa) were studied in 36 Japanese patients with pulmonary sarcoidosis, aged
      48.1+/-15.3 yrs (mean+/-SD), 15 males and 21 females. During the study the
      patients were on a daily diet with 500 mg calcium and 1000 mg phosphorus for a
      total of 6 days. sCa2+ was above the normal range (>1.26 mmol x L(-1)) in 10
      patients (27.8%), 12 patients (33.3%) were hypercalciuric, and 16 patients
      (44.4%) showed alteration in calcium metabolism, with an increase in values of
      sCa, sCa2+ or uCa. There was a significant correlation between sCa2+ and
      s1,25(OH)2D3 (p<0.001), as well as between sCa2+ and sACE (p<0.001). s1,25(OH)2D3
      in patients with extrathoracic involvement (ETI) tended to be higher than in
      patients without ETI. sCa2+ was less than 1.23 mmol x L(-1) (p<0.05) in the
      majority of patients without ETI, and sCa2+ was less than 1.24 mmol x L(-1) in
      the majority of normocalciuric patients. In conclusion, a disease-related
      alteration in calcium metabolism was seen in about 40% of patients with
      sarcoidosis, and 1,25-dihydroxyvitamin D probably plays a crucial role in this
      abnormality. The serum concentration of ionized calcium was considered to be a
      useful index for the disease activity of sarcoidosis.

PMID- 9648950
TI  - Asbestosis, pleural plaques and diffuse pleural thickening: three distinct benign
      responses to asbestos exposure.
AB  - The aim of this study was to investigate by computed tomography (CT) whether
      asbestosis, diffuse pleural thickening and/or pleural plaques are statistically
      associated. We also tried to find criteria to differentiate between diffuse and
      circumscribed pleural thickening. From 231 exposed workers, only those subjects
      whose radiograph showed neither bilateral calcified pleural plaques nor small
      pulmonary opacities higher than 1/1 grade according to the 1980 International
      Labour Office (ILO) Classification were considered. Scans were assessed for the
      presence of subpleural curvilinear lines, septal and intralobular lines,
      parenchymal bands, honeycombing, rounded atelectasis, pleural plaques and diffuse
      pleural thickening. CT scans revealed pleural and/or lung abnormalities in 99
      workers. Pleural plaques were unilateral in one-third of cases with plaques.
      Diffuse pleural thickening, parenchymal bands and rounded atelectasis were
      unilateral in, respectively, 62 and 69 and 75% of cases with the abnormality.
      Septal and intralobular lines, and honeycombing were always bilateral. CT signs
      could be grouped into three patterns: 1) septal and intralobular lines, and
      honeycombing corresponding to pulmonary fibrosis; 2) pleural plaques
      corresponding to parietal pleural fibrosis; and 3) diffuse pleural thickening,
      rounded atelectasis and parenchymal bands corresponding to visceral pleural
      fibrosis. In these workers with a normal or near-normal radiograph, three groups
      of subjects with different responses were distinguished. Crow's feet and rounded
      atelectasis help to differentiate plaques from diffuse thickening.

PMID- 9648951
TI  - Postoperative lung injury and oxidative damage in patients undergoing pulmonary
      resection.
AB  - Postpneumonectomy pulmonary oedema (PPO) complicates a significant number of
      thoracic surgical procedures involving lung resection and in its extreme form is
      indistinguishable from the acute respiratory distress syndrome. This study
      investigated the possibility that ischaemia-reperfusion (I-R) injury contributes
      to PPO via the production of damaging reactive oxygen species. In a prospective,
      observational, comparative study, patients undergoing pneumonectomy, lobectomy,
      or wedge resection or open lung biopsy were investigated for perioperative
      changes in lung function indicative of lung injury and changes in plasma indices
      of oxidative damage. Significant percentage perioperative falls in plasma protein
      thiol levels (-17.9+/-7.0% for pneumonectomy, -24.3+/-5.5% for two-lobe lobectomy
      and -10.2+/-2.2% for one-lobe lobectomy, p<0.05) and rises in plasma protein
      carbonyl levels (26.2+/-10.5% for pneumonectomy, p<0.05, 9.8+/-7.0% for two-lobe
      lobectomy and 5.0+/-2.7% for one-lobe lobectomy) were identified, but not in
      patients undergoing biopsy or wedge resection. Plasma myeloperoxidase levels rose
      in all groups, but not significantly. The carbon monoxide transfer coefficient
      (K(CO)) fell significantly in patients undergoing lobectomy (p<0.05) but not in
      those undergoing wedge resection, lung biopsy or pneumonectomy. Changes in
      markers of oxidative protein damage occurred in patients undergoing lung
      resection, although the gas transfer coefficient fell significantly only
      following lobectomy. Oxidative damage occurs during pulmonary resection, although
      associated effects on gas exchange are seen only after lobectomy.

PMID- 9648952
TI  - Superimposing positive end-expiratory pressure during partial liquid ventilation
      in experimental lung injury.
AB  - This study was undertaken to determine the effects of superimposing incremental
      levels of positive end-expiratory pressure (PEEP) during partial liquid
      ventilation (PLV) on gas exchange, respiratory mechanics and morphological
      changes in experimental acute lung injury (ALI). In a prospective trial, six pigs
      weighing 30+/-5 kg (mean+/-SD) were tracheotomized, submitted to pressure
      controlled mechanical ventilation (pc-CMV) and depleted of surfactant by lung
      lavage. Animals were then mechanically ventilated with three levels of PEEP: 0.5,
      1.0 and 1.5 kPa. PLV was then initiated by intratracheal instillation of 30 mL x
      kg(-1) perfluorocarbon, followed by pc-CMV with PEEP 0.5, 1.0 and 1.5 kPa.
      Computed tomography (CT)-based analyses of lung volumes and density were obtained
      after lung lavage, in PLV and during the combined application of PLV and PEEP.
      Simultaneously, haemodynamics, gas exchange, dynamic compliance (Cdyn) and
      dynamic resistance (Rdyn) were determined. Statistical analysis was performed
      using multivariate analyses of variance for repeated measures (p<0.05). In ALI
      and before PLV, the application of PEEP significantly reduced cardiac output and
      intrapulmonary shunt. Arterial oxygen tension (Pa,O2) was increased from 6.9 kPa
      (52 (42, 54) mmHg) (median, (25th and 75th percentile)) to 8.6 kPa (65 (52, 133)
      mmHg) (PEEP 1.0 kPa) and 15.6 kPa (117 (90, 195) mmHg) (PEEP 15 kPa) (p<0.05).
      The lung volume obtained by CT increased, CT density was reduced (p<0.05), Cdyn
      tended to increase and Rdyn to decrease (nonsignificant). PLV increased arterial
      carbon dioxide tension and reduced pH (p<0.05). CT lung volume and lung density
      were increased (p<0.05). Superimposing PEEP on PLV increased Pa,O2 from 9.3 kPa
      (70 (52,124) mmHg) (PEEP 0.5 kPa) to 12.9 kPa (97 (55, 233) mmHg) (PEEP 1.0 kPa)
      and 403 kPa (303 (64, 426) mmHg) (PEEP 1.5 kPa) (p<0.05), but had no significant
      effect on CT lung volume and density. It was concluded that in experimental lung
      injury, positive end-expiratory pressure provided alveolar recruitment. The
      combined application of positive end-expiratory pressure and partial liquid
      ventilation significantly augmented oxygenation and might eventually allow either
      a reduction in the volumes of perfluorocarbons required, or a reduction in
      positive end-expiratory pressure necessary to maintain pulmonary gas exchange in
      acute lung injury.

PMID- 9648953
TI  - Secretory component production by human bronchial epithelial cells is upregulated
      by interferon gamma.
AB  - Secretory immunoglobulin A (S-IgA) participates in the first noninflammatory line
      of defence of the respiratory tract. S-IgA consists of dimeric IgA (dIgA)
      produced by plasma cells and secretory component (SC) produced by epithelial
      cells. This study compared SC production by primary cultures of human bronchial
      epithelial cells (HBEC) and by respiratory epithelial cell lines. Among the cell
      lines, A549 did not produce detectable SC, 16HBE produced very low levels of SC,
      while CALU-3 produced significant levels of SC. HBEC produced SC in nonpolarized
      and polarized primary cultures, where it was secreted apically. Polarized HBEC
      transcytosed radiolabelled and cold dIgA, resulting in the presence of S-IgA in
      their apical media. SC production and IgA transcytosis by polarized HBEC were
      upregulated by interferon-gamma (IFN-gamma) after 48 h. By reverse transcription
      polymerase chain reaction, no SC messenger ribonucleic acid (mRNA) was detected
      in A549 and 16HBE, while SC mRNA in CALU-3 was comparable to that of HBEC
      incubated for 48 h with IFN-gamma. By immunocytochemistry, HBEC expressed SC
      immunostaining and its intensity increased after 48 h with IFN-gamma. It is
      concluded that human bronchial epithelial cells produce secretory component and
      transcytose dimeric immunoglobulin A in vitro. These processes were apically
      polarized and upregulated by interferon-gamma. Among the cell lines studied, only
      CALU-3 expressed secretory component-messenger ribonucleic acid and produced
      detectable secretory component.

PMID- 9648954
TI  - Orientation and presence of epithelium are key to endotoxin-induced neutrophil
      migration.
AB  - The mechanisms by which endotoxins mediate neutrophil transepithelial migration
      and lung inflammation are unclear. It was hypothesized that both the presence and
      orientation of epithelial cells are critical to endotoxin-induced neutrophil
      migration. Neutrophil migration was compared through naked filters and filters
      with A549 lung epithelial monolayers grown on the upper and lower surface of
      permeable filters to simulate the apical and basal directional movement of
      neutrophils, respectively. The endotoxin, Pseudomonas aeruginosa
      lipopolysaccharide, was placed below the filter, acting as either a basal or an
      apical stimulus. Endotoxin without serum failed to stimulate neutrophil
      migration. In the presence of 1% human serum, endotoxin-induced neutrophil
      migration through naked filters was dose dependent. Endotoxin-induced neutrophil
      migration across A549 monolayers was minimal when the monolayers were cultured on
      the upper surface of the filters (basal stimulus). In contrast, neutrophil
      transepithelial migration was much greater and dependent on both dose and time
      when the monolayer was cultured on the lower surface of the filter (basal to
      apical neutrophil directional movement). Furthermore, enhanced neutrophil
      transepithelial migration was greater with an apical than with a basal stimulus.
      Endotoxin-induced neutrophil transepithelial migration was markedly inhibited
      (>95%) by actinomycin D pretreatment of the monolayers, suggesting the necessity
      for intact protein synthesis capacity of the A549 cells. Thus, both the presence
      and orientation of airway epithelium are key in supporting endotoxin-mediated
      lung neutrophilic responses.

PMID- 9648955
TI  - Atopy in cough sensitivity to capsaicin and bronchial responsiveness in young
      females.
AB  - We have shown previously that female sex is a determinant of cough sensitivity to
      inhaled capsaicin, but the relationship between atopy and the cough sensitivity
      has not been examined. The capsaicin cough threshold, defined as the lowest
      concentration of capsaicin causing five or more coughs, nonspecific bronchial
      responsiveness, defined as the provocative concentration of methacholine causing
      a 20% fall in the forced expiratory volume in one second (PC20), total
      immunoglobulin E (IgE) and specific IgEs to eight common aeroallergens (house
      dust 1, 2 and 6, Dermatophagoides pteronyssinus and D. farinae, Japanese cedar,
      ragweed and orchard grass) in the serum were measured in 71 nonsmoking, healthy
      young women aged 20.6+/-0.1 yrs (mean+/-EM). A structured interviewer-led
      questionnaire on allergic diseases revealed that one and six subjects had mild
      current and past asthma, respectively. These seven subjects were excluded from
      the data analysis. PC20 was significantly lower in 42 subjects showing a positive
      specific IgE than in 22 subjects showing a negative specific IgE to any of the
      eight allergens (p<0.05), while the capsaicin cough threshold was not
      significantly different between the subgroups. PC20 was significantly lower in
      subjects with positive specific IgE to Dermatophagoides and house dust, but not
      to the three kinds of pollen examined. It was confirmed that atopy indicated by
      specific immunoglobulin E to mite-related antigens, but not to pollen antigens,
      is associated with nonspecific bronchial responsiveness, and it is suggested that
      atopy is not a determinant of airway cough sensitivity in healthy, nonasthmatic
      subjects.

PMID- 9648956
TI  - Eosinophilic inflammation in cough variant asthma.
AB  - Eosinophils are considered to play a central pathogenetic role in asthma. We
      previously reported that sputum eosinophilia was observed in patients with cough
      variant asthma (CVA), as well as in "classic" asthma with wheezing. This study
      was undertaken to further investigate the involvement of eosinophils in CVA. The
      serum eosinophil cationic protein (ECP) level, the percentage of eosinophils in
      bronchoalveolar lavage (BAL) fluid, and the number of eosinophils in bronchial
      biopsy specimen were examined in 14 patients with CVA, 21 with classic asthma,
      and in seven healthy controls. For the two asthmatic groups, the clinical
      severity was classified with scores of 1-3. Pulmonary function and bronchial
      responsiveness were not significantly different between the patients with classic
      asthma and those with CVA. BAL, tissue eosinophil and serum ECP were all
      significantly increased in both classic asthma and CVA when compared with the
      controls but were not different between classic asthma and CVA. In both groups of
      asthmatics, the clinical severity significantly correlated with serum ECP and
      tissue eosinophils. In conclusion, eosinophilic inflammation is involved in cough
      variant asthma as well as in classic asthma. Anti-inflammatory treatment may be
      essential in patients with CVA, as in those with classic asthma.

PMID- 9648957
TI  - No effects of high-dose omeprazole in patients with severe airway
      hyperresponsiveness and (a)symptomatic gastro-oesophageal reflux.
AB  - Acid gastro-oesophageal reflux may aggravate respiratory symptoms in patients
      with asthma and chronic obstructive pulmonary disease (COPD) by increasing airway
      hyperresponsiveness through vagally-mediated pathways. We wanted to determine
      whether elimination of acid reflux could improve symptoms in such patients. In a
      randomized, double-blind, placebo-controlled study, 36 allergic and nonallergic
      subjects (17 males and 19 females, mean age 52 yrs), with airway obstruction and
      severe airway hyperresponsiveness despite maintenance treatment with an inhaled
      corticosteroid and with increased acid gastro-oesophageal reflux, were treated
      either with omeprazole, 40 mg b.i.d., or placebo for 3 months. Primary endpoints
      were: airway hyperresponsiveness, as determined by the provocative concentration
      of methacholine producing a 20% fall in forced expiratory volume in one second
      (PC20); and airway obstruction. Secondary endpoints were: peak expiratory flow
      variability; reversibility to inhaled ipratropium bromide as a parameter of vagal
      activity; asthma symptoms scores; and medication used. Reflux was measured by 24
      h ambulatory intraoesophageal pH measurement. Omeprazole, 40 mg b.i.d., for 3
      months had no beneficial effect on any of the pulmonary parameters, despite its
      profound effect on acid reflux and improvement of reflux symptoms scores,
      compared to placebo. The results of this study do not support a role for
      intensive antireflux therapy to improve pulmonary symptoms and function in
      patients with asthma and chronic obstructive pulmonary disease, who have severe
      airway hyperresponsiveness despite maintenance treatment with inhaled
      corticosteroids.

PMID- 9648958
TI  - Attenuation of isocapnic hyperpnoea-induced guinea-pig bronchoconstriction by
      chronic hypoxia.
AB  - Chronic hypoxia has been shown to augment the production of antioxidants in rat
      lungs and to reduce airway hyperreactivity in patients with asthma. This study
      investigated indirectly whether this increase in antioxidants occurs in guinea
      pig lungs and whether the increased antioxidants affect hyperpnoea-induced
      bronchoconstriction (HIB). Guinea-pigs were divided into four groups: control
      (n=8); chronic hypoxia (n=7); capsaicin pretreatment (n=7); and capsaicin
      pretreatment plus chronic hypoxia (n=8). Control animals were not treated.
      Animals in the hypoxia group were intermittently exposed to an ambient pressure
      of 380 mmHg for 7 days. A five day pretreatment of capsaicin was used to deplete
      tachykinins. In the last group, animals were pretreated with capsaicin, followed
      by a seven day hypoxic exposure. On the day of the study, airway function was
      examined in the anaesthetized and paralysed animal. Fifteen minutes of hyperpnoea
      caused marked decreases in the maximal expiratory flow rate at 15% vital
      capacity, forced expiratory volume in one second, and dynamic respiratory
      compliance, indicating HIB. This HIB and plasma substance P levels were
      significantly attenuated by chronic hypoxia, capsaicin pretreatment, and
      capsaicin pretreatment plus chronic hypoxia. Furthermore, chronic hypoxia
      attenuated airway constriction induced by xanthine-xanthine oxidase. The results
      suggest that chronic hypoxia attenuates hyperpnoea-induced bronchoconstriction
      via a decrease in the oxygen radical-mediated release of tachykinins.

PMID- 9648959
TI  - Bronchodilator response to salbutamol after chronic dosing with salmeterol or
      placebo.
AB  - It has been hypothesized that regular inhaled beta2-agonist therapy causes
      desensitization of beta2-receptors. The aim of this study was to define whether
      beta2-receptor desensitization occurs after treatment with the long-acting beta2
      agonist salmeterol, assessed by measuring the bronchodilator response to
      cumulative repeated doses of inhaled salbutamol before and after treatment. Forty
      nine stable adult patients with asthma were randomized to receive either
      salmeterol 50 microg b.d. or placebo b.d. from an Accuhaler for 4 weeks after an
      initial 2 week run-in period without beta2-agonists. All patients were receiving
      inhaled corticosteroids. Bronchodilator responsiveness to cumulative repeated
      doses of inhaled salbutamol were measured before and 12 and 36 h after the last
      dose of study treatment. The primary efficacy endpoint was the peak forced
      expiratory volume in one second (FEV1) response before and after treatment. There
      were no significant differences between the two treatment groups in the absolute
      peak FEV1 or maximal peak expiratory flow (PEF) results 12 or 36 h after the last
      dose of study treatment. Significantly higher clinic lung function and diary card
      parameters were noted in the salmeterol group when compared to the placebo
      treated patients, demonstrating the beneficial effects of regular salmeterol.
      Regular salmeterol usage did not lead to reduced efficacy of usual or higher than
      usual doses of salbutamol.

PMID- 9648960
TI  - Bronchodilator response to salbutamol after spontaneous recovery from nonspecific
      bronchial provocation tests in asthma.
AB  - Assessment of airway responsiveness by bronchoprovocation and bronchodilatation
      tests is important in the diagnostic work-up protocol of bronchial asthma and it
      would be convenient to undertake both tests on the same occasion. However, it is
      not known whether this can be done accurately. Therefore, this study evaluated
      the effect of a prior bronchial provocation test on the bronchodilator response
      to salbutamol after spontaneous recovery of the forced expiratory volume in one
      second (FEV1) in a group of asthmatic subjects. On two separate occasions at the
      same time of day, concentration-response studies with inhaled histamine or
      methacholine, or a sham challenge with normal saline were carried out in a
      blinded, randomized manner. Changes in airway calibre were followed as FEV1 and
      agonist responsiveness expressed as the provocative concentration causing a 20%
      fall in FEV1 (PC20). After either spontaneous recovery or a fixed-duration wait
      of 45 min (when appropriate), the subjects received 2x100 microg of salbutamol
      from a metered dose inhaler with a spacer. The bronchodilator response to
      salbutamol was expressed as a percentage of initial FEV1 (deltaFEV1% init).
      Bronchial challenge with both agonists failed to alter significantly the airway
      response to salbutamol, with the deltaFEV1% init mean value (range) being 16.9%
      (9.0-31.9) and 17.5% (11.6-31.2) on the sham and histamine/methacholine challenge
      day respectively. It was shown that the degree of bronchodilatation achieved
      after salbutamol 200 microg is not affected by prior bronchoprovocation testing
      when enough time is allowed for the airways to recover spontaneously to baseline
      forced expiratory volume in one second. Thus evaluation of airway responsiveness
      by both bronchial provocation tests and bronchodilator testing can be assessed
      reliably within a few hours in asthmatic patients.

PMID- 9648961
TI  - Tolerance to the protective effects of salmeterol on methacholine-induced
      bronchoconstriction: influence of inhaled corticosteroids.
AB  - Long-acting beta2-adrenoceptor agonists such as salmeterol reduce airway
      responsiveness for at least 12 h, but this effect seems to decrease with regular
      use. We evaluated the time-course of the protective effects of salmeterol on
      methacholine-induced bronchoconstriction, its modulation by inhaled
      corticosteroids (ICS) and its influence on asthma control. Thirty two subjects
      (13 males and 19 females) with mild to moderate stable asthma were divided into
      two groups according to their medication needs: bronchodilators (BD) alone (n=16)
      or with ICS (n=16). After a 2 week run-in period, a double-blind crossover study
      was conducted. Subjects from both groups received salmeterol 50 microg b.i.d. or
      a placebo for 4 weeks each in random order, separated by a 2 week washout period.
      The provocative concentration of methacholine causing a 20% fall in forced
      expiratory volume in one second (PC20) was measured before and after each
      treatment period, 1 h prior to inhalation of salmeterol or placebo and 1 and 12 h
      after. Baseline forced expiratory volume in one second (FEV1) increased
      significantly after salmeterol, both after the first dose and at 4 weeks (BD
      group: 19 and 17%; ICS: 22 and 13%). On the first day of administration,
      salmeterol provided significant protection in both groups up to 12 h with a PC20
      before and 1 and 12 h postdose of 2.2, 21.7 and 12.4, mg x mL(-1), respectively,
      in the BD group and 2.1, 11.6 and 55 mg x mL(-1), respectively, in the ICS group.
      After 4 weeks, this effect was significantly attenuated in both groups with a
      PC20 before, 1 and 12 h postdose of 3.3, 10.9 and 7.1 mg x mL(-1), respectively,
      in the BD group and 2.1, 5.0 and 2.3 mg x mL(-1), respectively, in the ICS group.
      This loss of protective effect was of similar magnitude in both groups.
      Respiratory symptoms, rescue beta2-agonist use and baseline FEV1 did not change
      significantly throughout the study in both groups. In conclusion, the
      bronchoprotective effect of salmeterol decreased with regular use both 1 and 12 h
      postdose; inhaled corticosteroids did not prevent this reduction. However, the
      development of tolerance was not associated with loss of asthma control.

PMID- 9648962
TI  - Platelet-activating factor increases leukotriene B4 release in stimulated
      alveolar macrophages from asthmatic patients.
AB  - This study was designed to examine further the role of platelet-activating factor
      (PAF) in asthma, comparing leukotriene B4 (LTB4) release, 5-lipoxygenase activity
      and intracellular calcium levels ([Ca2+]i) in macrophages. LTB4 and other
      lipoxygenase metabolites in macrophages in bronchoalveolar lavage fluids obtained
      from 23 asthmatic patients and 20 control subjects were measured by reverse-phase
      high-performance liquid chromatography. [Ca2+]i was monitored using the
      fluorescent probe fura-2. The basal LTB4 release of resting macrophages was not
      different between groups (0.02+/-0.01 versus 0.05+/-0.02 ng x 10(-6) cells). When
      stimulated with calcium ionophore A23187 (2.5 microM), however, macrophages from
      asthmatic patients released more LTB4 than cells from control subjects (30.2+/
      3.4 versus 13.7+/-2.1 ng x 10(-6) cells). Although PAF alone did not alter LTB4
      release, it enhanced the response to subsequent A23187 stimulation. This effect
      was noted following short treatment (i.e., 5 min) at concentrations of > or =1.0
      microM PAF, with the maximal effect noted after treatment with 5.0 microM PAF +
      2.5 microM A23187 (105.1+/-6.7 versus 15.3+/-2.6 ng x 10(-6) cells). Treatment of
      macrophages with PAF also increased 5-lipoxygenase activity and [Ca2+]i more in
      cytosols from asthmatic patients than in cytosols from control subjects. These
      findings support a role of intracellular calcium in the activation of 5
      lipoxygenase which, in turn, augments the release of leukotriene B4. Because
      levels of platelet-activating factor may be increased in the lung during asthma
      and can increase the subsequent release of a chemotactic mediator leukotriene B4,
      from macrophages, these findings suggest that platelet-activating factor may
      prime the constitutive cells of the lung to augment inflammatory effects
      important in the pathogenesis of asthma.

PMID- 9648963
TI  - Effect of slow-release theophylline on nasal antigen challenge in subjects with
      allergic rhinitis.
AB  - It has been recognized recently that theophylline possesses anti-inflammatory
      effects that could be of clinical interest in patients with airway inflammatory
      diseases such as asthma and allergic rhinitis (AR). The aim of the present study
      was to explore the effect of theophylline on the nasal eosinophilic inflammatory
      response following allergen challenge in patients with AR. Fourteen subjects
      suffering from seasonal rhinitis with an early reaction after nasal allergen
      provocation were challenged outside the pollen season after pretreatment for 3
      weeks with placebo or slow-release theophylline (Euphylong in a randomized double
      blind, cross-over study. Nasal blocking index (NBI), nasal airway resistance and
      symptoms were recorded before, and 1 and 5 h after challenge; additionally, nasal
      lavage fluid was collected before, as well as 1 and 5 h after challenge.
      Eosinophil cationic protein (ECP) was measured in the lavage as well as the
      number of eosinophils before, and 1 h and 5 h after allergen challenge. After 3
      weeks of treatment, baseline concentrations of ECP in nasal lavage amounted to
      826+/-329 ng x L(-1) (placebo) and 936+/-351 ng x L(-1) (theophylline). The ECP
      levels did not increase during the early phase response. Five hours after
      challenge, ECP in the placebo group increased markedly (p<0.01), whereas no
      significant increase was observed during theophylline treatment. In parallel, the
      number of eosinophils in the nasal lavage fluid was lower during theophylline
      treatment. Additionally, theophylline therapy also significantly reduced the
      nasal symptoms and had some protective effect against nasal obstruction following
      allergen challenge. These results confirm the anti-inflammatory effects of
      theophylline and suggest that these effects may be of clinical benefit in
      patients with allergic rhinitis.

PMID- 9648964
TI  - Fine particle mass from the Diskus inhaler and Turbuhaler inhaler in children
      with asthma.
AB  - The study aimed to investigate dose consistency and particle distribution from
      the dry powder inhalers Diskus and Turbuhaler. Full profiles of inhalation
      pressure versus time were recorded in 18 4 yr old and 18 8 yr old asthmatic
      children through Diskus and Turbuhaler inhalers. These data were used in an
      inhalation profile simulator to assess drug delivery from both a Diskus inhaler
      and a Turbuhaler inhaler, and in particular to assess the proportion of drug
      emitted in the coarse (>4.7 microm) and fine (<4.7 microm) particle size range
      from each type of inhaler. The inhalation profile more accurately represents the
      changes in flow rate over time through the device than the constant flow rate
      usually applied with an impactor alone. The aerosol cloud was released before the
      peak inspiratory effort had been achieved and accordingly the early part and not
      the peak of the inspiratory performance is a determinant of the quality of the
      aerosol. The mean (SD) amount of drug in large particles (>4.7 microm), fine
      particles (<4.7 microm) and very fine particles (<2.1 microm) in percentage of
      label claim from the Fluticasone Diskus was 72 (5), 15 (2) and 2 (1) from the 4
      yr old children and 71 (3), 18 (2) and 2 (1) from the 8 yr old children,
      respectively. Similar particle fractions from the Budesonide Turbuhaler were 35
      (9), 21 (10) and 7 (5) from 4 yr old children and 30 (7), 32 (9) and 12 (6) from
      8 yr old children. In conclusion, the Diskus inhaler provides an improved dose
      consistency through the varying age groups and inspiratory flow performances when
      compared to the Turbuhaler in terms of the proportion of the dose emitted at each
      particle size. This improvement is at the expense of a low fine particle mass and
      a high proportion of coarse particles from the Diskus as compared with the
      Turbuhaler.

PMID- 9648965
TI  - Prospective evaluation of World Health Organization criteria to assist diagnosis
      of tuberculosis in children.
AB  - Because of the difficulty in confirming childhood tuberculosis (TB), the World
      Health Organization (WHO) proposes a hierarchical approach to diagnosis using
      history and certain clinical features to help to improve the control of TB in
      communities. The objective of this study was to evaluate prospectively in
      children the diagnostic value of recent weight loss or failure to gain weight
      adequately, cough or wheezing for >2 weeks and recent household contact with an
      adult case of pulmonary TB. These evaluations were performed in 627 children
      presenting to the paediatric outpatient department of a tertiary hospital
      situated in the Western Cape Province of South Africa and serving a community
      with a very high incidence of TB (>1,000 per 100,000). If at least one of the
      criteria was present, the diagnosis of TB was investigated further by clinical
      investigation, Mantoux test, chest radiography and TB culture from gastric
      aspirate. One or more of the proposed criteria for diagnosing TB in childhood
      were present in 206 children (33%). TB confirmed by culture of Mycobacterium
      tuberculosis from gastric aspirate was found in 10 children (5%). After
      diagnostic work-up, 23 children (11%) were considered to have probable TB,
      whereas 173 (84%) were, after follow-up of 8 weeks, thought not to have TB. In
      this study the simultaneous presence of the three WHO criteria for suspecting TB
      had a positive predictive value of 63%. These results should assist in the more
      precise delineation of the predictive value of the proposed World Health
      Organization approach to the diagnosis of tuberculosis in childhood.

PMID- 9648966
TI  - Influence of correction of flow limitation on continuous positive airway pressure
      efficiency in sleep apnoea/hypopnoea syndrome.
AB  - We evaluated the efficiency of two different treatment procedures with continuous
      positive airway pressure (CPAP) on sleep, nocturnal breathing characteristics and
      daytime vigilance in 18 newly diagnosed patients with untreated sleep
      apnoea/hypopnoea syndrome (SAHS) randomly allocated to two different groups. In
      group I, the positive pressure (PP) level was set to suppress flow limitation
      (PFL), while in group II the PP was set at a level that eliminated only
      apnoea/hypopnoea and snoring (PAHS). At the end of a 3 week period of home CPAP
      therapy, a follow-up sleep study, vigilance and cognitive tests were made.
      Overall, PFL was significantly higher than PAHS values (PFL: 10.42.6 cmH2O; PAHS:
      8.9+/-2.6 cmH2O; p<0.01, mean+/-SD). We found no difference in sleep quality,
      nocturnal saturation and apnoea/hypopnoea index, or in daytime vigilance tests
      between the two groups at the end of the treatment period. However, there was a
      significantly greater scattering in the changes of sleep latency in group II than
      in group I. This was associated with a significant difference in the daily
      duration of nasal CPAP use between the two groups (group I: 7.29+/-0.95 h x day(
      1); group II: 6.01+/-0.94 h x day(-1); p=0.01) and with a positive correlation
      between final maintenance of wakefulness test values and the duration of CPAP use
      (p<0.05; r=0.55). These results tend to show that correcting flow limitation is
      associated with a higher observance and a more important efficiency in
      normalizing daytime vigilance than with conventional nasal continuous positive
      airway pressure.

PMID- 9648967
TI  - Forced oscillation technique for the evaluation of severe sleep apnoea/hypopnoea
      syndrome: a pilot study.
AB  - The forced oscillation technique (FOT) is a noninvasive method of potential
      clinical interest for quantitatively assessing airway mechanics during sleep. We
      investigated the applicability of FOT as a diagnostic tool for noninvasive
      assessment of airflow obstruction in patients with sleep apnoea/hypopnoea
      syndrome (SAHS) during sleep. In seven patients previously diagnosed with severe
      SAHS (mean+/-SD apnoea/ hypopnoea index (AHI) 67+/-14) we performed a full
      polysomnography (PSG) together with on-line measurement of respiratory impedance
      (IZI) using FOT. For each patient we determined: 1) number of respiratory events
      conventionally detected by full PSG, those obtained by FOT and their degree of
      concordance; and 2) the characteristics and values of IZI during the respiratory
      events. FOT was well tolerated and easily applied in conjunction with a
      conventional sleep setup. The mean number of respiratory events x h(-1) detected
      by PSG and FOT were 55+/-16 and 58+/-17, respectively, with a strong concordance.
      IZI increased from a baseline of 11+/-4 to 50+/-20 cmH2O x L(-1) x s during
      apnoea (mean+/-SD). In all but one patient intermittent increases of IZI occurred
      immediately before each obstructive apnoea. In four patients, the increases of
      IZI developed at end-expiration whereas in two others occurred during
      inspiration. During hypopnoea most of the patients showed decreases of IZI during
      expiration. In conclusion, forced oscillation technique can be used as a
      noninvasive and complementary tool for the diagnosis of respiratory events and
      provides an on-line quantitative approach for continuous monitoring of airflow
      obstruction during sleep in patients with sleep apnoea/hypopnoea syndrome.

PMID- 9648968
TI  - Spectral analysis of wakefulness and REM sleep EEG in patients with sleep apnoea
      syndrome.
AB  - Neuropsychological investigations of patients with obstructive sleep apnoea
      syndrome (OSAS) have shown impairments in such basic functions as memory,
      attention and executive control. Since executive functions are known to be
      dependent on the integrity of the frontal lobe, it was hypothesized that OSAS may
      be associated with hypoxaemic frontal lobe dysfunction. To test this hypothesis,
      21 apnoeic patients and 10 normal controls were studied with quantitative
      electroencephalographic (EEG) methods during rapid eye movement (REM) sleep, when
      most apnoeic events occur and during wakefulness. In apnoeic patients, EEG
      slowing in REM sleep was observed over frontal, central and parietal regions,
      while EEG slowing during wakefulness was observed over all cortical regions
      examined. A positive correlation was found between EEG slowing during wakefulness
      and oxygen desaturation during the night. Contrary to the hypothesis, these
      electroencephalographic changes were not localized only to the frontal region.
      This result may explain the wide range of neuropsychological deficits noted in
      patients with obstructive sleep apnoea syndrome, in addition to their poor
      performance in tasks of executive functioning.

PMID- 9648969
TI  - A comparison of three methods of measuring 99mTc-DTPA lung clearance and their
      repeatability.
AB  - The lung clearance of technetium-99m diethylenetriamine penta-acetic acid (99mTc
      DTPA) is a measure of respiratory epithelial permeability. Many factors may
      contribute to the wide range of normal values, including the method of correction
      for background activity. The aim of this study was to compare three methods of
      analysis, including their repeatability. 99mTc-DTPA lung clearance imaging was
      performed on eight nonsmokers (age 32+/-2 yrs, forced expiratory volume in one
      second (FEV1) 102.8+/-3.3% predicted yrs, mean+/-SEM and seven smokers (age 46+/
      4 yrs, p<0.01, versus nonsmokers; FEV1 88.9+/-8.9%, p<0.05 versus nonsmokers) on
      two occasions each. The smokers were asked to refrain from smoking for 12 h. An
      uncorrected analysis was compared with two methods corrected for recirculating
      background activity using an intravenous correction and inter-renal and shoulder
      background regions of interest. The uncorrected method gave higher mean values
      for 50% lung clearance of 99mTc-DTPA (t50) values than the inter-renal (p<0.001)
      and shoulder (p<0.001) methods of correction in nonsmokers and the inter-renal
      method gave lower values than the shoulder-corrected method (p<0.05). In smokers
      there was no difference. There were no differences in mean t50 values obtained on
      two separate visits. There was no difference in the repeatability of the three
      methods of analysis. The three methods of analysis produced comparable results
      with no differences in repeatability.

PMID- 9648970
TI  - Common fears of patients undergoing bronchoscopy.
AB  - In the world of medical literature, little has been reported about the fears of
      patients undergoing bronchoscopy. The aim of this study was to identify the
      common fears of patients undergoing fibreoptic bronchoscopy and to determine
      whether any factors might contribute to reducing these fears. One hundred and
      four consecutive patients undergoing bronchoscopy were interviewed. Sixty one
      patients expressed fear about the procedure, as follows: afraid of pain (33);
      afraid of breathing difficulties (11); afraid of oropharyngeal irritation (5);
      afraid of the bronchoscopy findings (2); afraid of sedation, cross-infection and
      nasal lignocaine spray, respectively (3); and unable to be specific (7). There
      was no difference between the "no fear" and "fearful" groups in ethnicity, source
      of referral, education, previous endoscopy, doctors' explanation and the
      patients' understanding of the procedure and its indication. "Fearful" patients
      were significantly younger (t=2.082, p=0.037) and female (chi2=4.180, p=0.038).
      Doctors were more likely to explain the indication for bronchoscopy than how it
      would be performed (chi2=6.403; p=0.011), and patients were more likely to
      understand why they needed a bronchoscopy than how it would be performed
      (chi2=21.505; p<0.001). Fear preceding bronchoscopy is independent of patients'
      demographic features except for age and gender. Doctors tend to explain "why" but
      not "how" the procedure is performed. Provision of detailed information about
      sensations that are likely to be experienced in bronchoscopy could be used to
      allay some of these common fears.

PMID- 9648971
TI  - Treatment of ventilatory failure in the Prader-Willi syndrome.
AB  - Hypercapnic respiratory failure is a common cause of death in the Prader-Willi
      syndrome. Its relationship to sleep-disordered breathing has not been established
      and there are no reports of its successful treatment. We have retrospectively
      reviewed the records of four patients with the syndrome, who developed
      ventilatory failure. Daytime arterial blood gas tensions and overnight oximetry
      traces before and during treatment were compared. Each patient had severe sleep
      disordered breathing in association with daytime ventilatory failure. The median
      overnight mean arterial oxygen saturation (Sa,O2) was 82% and the median minimum
      was only 41.5%. Initial treatment was with nasal intermittent positive pressure
      ventilation, and in each case the daytime arterial blood gas tensions were
      normalized. The patients were maintained on nasal continuous positive airway
      pressure at night after discharge. Compliance has been good, and at last follow
      up (after a median of 4.8 yrs) the daytime arterial gas tensions remained normal,
      while the median overnight mean arterial oxygen saturation was 95.5% and the
      median minimum was 84.5%. This study of patients with the Prader-Willi syndrome
      shows that daytime ventilatory failure is associated with sleep-disordered
      breathing. It can be reversed with nocturnal noninvasive ventilation and
      maintenance treatment with continuous positive airway pressure is well tolerated,
      with no deterioration in respiratory parameters.

PMID- 9648972
TI  - Pulmonary vascular disorders in portal hypertension.
AB  - The wide spectrum of pulmonary vascular disorders in liver disease and portal
      hypertension ranges from the hepatopulmonary syndrome characterized by
      intrapulmonary vascular dilatations, to pulmonary hypertension (portopulmonary
      hypertension), in which pulmonary vascular resistance is elevated. Since
      hepatopulmonary syndrome and portopulmonary hypertension have been reported in
      patients with nonhepatic portal hypertension, the common factor that determines
      their development must be portal hypertension. The clinical presentations are
      very different, with gas exchange impairment in the hepatopulmonary syndrome and
      haemodynamic failure in portopulmonary hypertension. The severity of
      hepatopulmonary syndrome seems to parallel the severity of liver failure, whereas
      no simple relationship has been identified between hepatic impairment and the
      severity of portopulmonary hypertension. Resolution of hepatopulmonary syndrome
      is common after liver transplantation, which has an uncertain effect in
      portopulmonary hypertension. The pathophysiology of both syndromes may involve
      vasoactive mediators and angiogenic factors.

PMID- 9648973
TI  - Effect of inhaled corticosteroids on bones and growth.
AB  - Inhaled corticosteroids are recognized as the most effective anti-inflammatory
      therapy in patients with asthma and their early introduction is recommended by
      national and international guidelines. Concerns have been raised about potential
      adverse effects of inhaled corticosteroids on bones and growth, as these appear
      to be more important clinically than effects on the hypothalamic-pituitary
      adrenal axis, which are more commonly measured. This review examines the effects
      of inhaled corticosteroids on biochemical bone markers, bone density and growth
      in adults and children with asthma, in view of the recent availability of a
      substantial amount of new clinical trial data. Examination of relevant
      retrospective and prospective data, involving 11 studies (1,240 patients) on
      biochemical bone markers and 14 studies (373 patients) on bone density over a
      wide dose range, have largely indicated no significant or clinically important
      effect on these measurements in adults or children with asthma. Markers of bone
      formation and resorption need to be measured concurrently for a reliable
      assessment of bone turnover to be made. Knemometry, measuring lower leg growth
      rate, is a sensitive technique for comparing the systemic activity of different
      inhaled corticosteroids, but does not relate to long-term growth. The majority of
      approximately 40 studies on inhaled corticosteroids and statural growth in
      children, over a wide recommended dose range, including a number of recent long
      term, prospective studies, demonstrate little or no effect. Children taking above
      recommended doses of inhaled corticosteroids should have their growth monitored
      using stadiometry at least every 6 months by trained personnel. Most of the areas
      reviewed, particularly the relatively new areas of biochemical bone markers and
      bone density, require further properly controlled, long-term, prospective
      investigation, although the long-term value of bone markers appears limited. In
      summary, the data as it currently stands, suggests that doses of inhaled
      corticosteroids up to 1,000 microg x day(-1) in adults and 400 microg x day(-1)
      in children have no significant effect on bones and growth in the large majority
      of patients with asthma.

PMID- 9648974
TI  - The role of "fear of corticosteroids" in nonparticipation in early intervention
      with inhaled corticosteroids in asthma and COPD in general practice.
AB  - Treatment of chronic airflow obstruction with inhaled corticosteroids at an early
      stage has been shown to preserve the lung function. We tested the hypothesis that
      "fear of corticosteroids" may be an important reason for nonparticipation in the
      Detection, early Intervention and Monitoring programme on Chronic obstruction
      pulmonary disease (COPD) and Asthma ("DIMCA") project. One thousand seven hundred
      and forty nine adult subjects from 10 general practices were invited to
      participate in the several parts of the "DIMCA" programme. Refusers were
      questioned about the reason(s) for nonparticipation. Together the screening,
      monitoring and three drug interventions of the study showed on average 25-35%
      refusers. The most frequent reasons for nonparticipation were absence of
      pulmonary symptoms and lack of time. For those invited to take part in one of the
      three drug interventions, "dislike of medication" was the most important reason
      for nonparticipation (33, 45 and 67% of the refusers). "Fear of corticosteroids"
      specifically was the reason for nonparticipation in 8% of the refusers on the
      basis of "dislike of medication". We concluded that a specific fear of
      corticosteroids was not a major obstacle for early intervention with inhaled
      corticosteroids.

PMID- 9648975
TI  - Occupational asthma caused by aluminium welding.
AB  - Work-related asthma has been documented in workers employed in the primary
      aluminium industry and in the production of aluminium salts. The role of
      aluminium in the development of occupational asthma has, however, never been
      convincingly substantiated. We investigated a subject who experienced asthmatic
      reactions related to manual metal arc welding on aluminium. Challenge exposure to
      aluminium welding with flux-coated electrodes, as well as with electrodes without
      flux, elicited marked asthmatic reactions. Manual metal arc welding on mild steel
      did not cause significant bronchial response. The results of inhalation
      challenges combined with exposure assessments provided evidence that aluminium
      can cause asthmatic reactions in the absence of fluorides. Awareness of this
      possibility may be relevant to the investigation of asthma in workers exposed to
      aluminium.

PMID- 9648976
TI  - Alpha-fetoprotein producing pulmonary blastoma in a patient with systemic
      sclerosis: pathogenetic analysis.
AB  - We describe a rare case of pulmonary blastoma complicated with systemic
      sclerosis. The serum alpha-fetoprotein level was elevated at presentation and the
      biopsied tumour stained positively against anti-alpha-fetoprotein antibody. The
      alpha-fetoprotein produced autonomously by tumour cells was of yolk-sac origin.
      Although the pathogenesis of pulmonary blastoma has not been clarified, we
      suggest that this pulmonary blastoma is a type of yolk-sac tumour.

PMID- 9648977
TI  - Bronchial stenosis and sclerosing mediastinitis: an uncommon complication of
      external thoracic radiotherapy.
AB  - The side-effects of radiation therapy on the bronchial tree or on the mediastinum
      are seldom reported. In this setting, we report a case of sclerosing
      mediastinitis with bronchial stenosis discovered 1 yr after external radiotherapy
      for lung cancer. The patient was treated with a Dumont stent and has so far had
      an uneventful further course for up to 42 months. Bronchial stenosis related to
      mediastinal fibrosis after radiotherapy has not been reported previously.

PMID- 9648978
TI  - An unusual case of Hughes-Stovin syndrome.
AB  - In 1959 HUGHES and STOVIN described a syndrome consisting of multiple pulmonary
      aneurysms and peripheral venous thrombosis. Since that time several cases of the
      Hughes-Stovin syndrome have been published. We present the case of a 25 yr old
      man who, in addition to the classical symptoms, had multiple aneurysms of the
      bronchial arteries, which were the cause of severe haemoptysis. An aneurysm of
      the left hepatic artery was also detected. To our knowledge this is the first
      description of aneurysms of the bronchial arteries in Hughes-Stovin syndrome.
      Bleeding was successfully treated by double embolization of bronchial arteries
      via transfemoral catheter.

PMID- 9648979
TI  - Comparative assessment of safety and efficacy of inhaled corticosteroids: report
      of a committee of the Canadian Thoracic Society.

PMID- 9648980
TI  - Evaluation of a commercial infant body plethysmography.

PMID- 9648981
TI  - Barrett's oesophagus: pathophysiology, diagnosis, and management.

PMID- 9648982
TI  - Gastric ulcer, atrophic gastritis, and intestinal metaplasia caused by
      Helicobacter pylori infection in Mongolian gerbils.
AB  - BACKGROUND: Helicobacter pylori infection is associated with gastroduodenal
      disease in humans. In this study we aimed to show this relationship directly in
      Mongolian gerbils. METHODS: The animals were challenged orally with H. pylori and
      killed 1, 2, 3, and 6 months after inoculation for histologic and anti-H. pylori
      antibody titer examination. RESULTS: The spiral bacteria were observed in the
      mucus and gastric pits of all infected animals. A severe infiltration of the
      lamina propria by polymorphonuclear and mononuclear cells was seen 1 month after
      H. pylori inoculation. The submucosa was infiltrated by mainly mononuclear cells
      with formation of lymphoid follicles. Erosion of the gastric mucosa appeared soon
      after inoculation, whereas gastric ulcers, gastritis cystica profunda, and
      atrophy with goblet cell metaplasia occurred between 3 and 6 months after
      inoculation. In the duodenal mucosa a mild inflammatory cell infiltration with
      ballooning and diminished number of duodenal glands was seen. The IgG anti-H.
      pylori antibody titer increased gradually after 2 months of inoculation.
      CONCLUSIONS: Since the gastritis, gastric ulcers, atrophic gastritis, and
      intestinal metaplasia that developed in Mongolian gerbils were similar to those
      observed in humans, this model may be useful to study the therapy of gastric
      ulcer and, with a longer observation period, to confirm a possible relationship
      between H. pylori and malignancy.

PMID- 9648983
TI  - Effects of Helicobacter pylori eradication on gastric function indices in
      functional dyspepsia. A prospective controlled study.
AB  - BACKGROUND: To date, it is unclear whether Helicobacter pylori infection is
      associated with disturbances of gastric emptying or acid secretion in patients
      with functional dyspepsia (FD). Our aim was to investigate whether, in the long
      run, cure of H. pylori infection significantly influences gastric emptying of
      solids, acid secretion, and gastrin and pepsinogen I (PGI) release in patients
      with FD. METHODS: Thirty-eight consecutive H. pylori-positive patients with FD,
      whose complaints were scored for severity and frequency on the basis of a
      validated symptom questionnaire, were initially enrolled in the study. They were
      randomized to receive an eradicating regimen consisting of omeprazole plus
      clarithromycin and tinidazole for 1 week or full-dose ranitidine for 3 weeks. In
      33 patients (18 H. pylori-cured and 15 with persistent infection) basal and
      pentagastrin-stimulated acid secretion, fasting and meal-induced gastrin
      concentrations, fasting serum PGI levels, and gastric emptying of solids were
      determined before and 6 months after therapy. RESULTS: In the 18 H. pylori-cured
      patients meal-induced gastrin and fasting PGI levels were significantly reduced
      after 6 months as compared with pretreatment values (peak serum gastrin, 76.0 +/-
      23.4 versus 111.9+/-37.4 pg/ml; PGI, 57.1+/-23.4 versus 72.9+/-29.1 ng/ml),
      whereas they remained virtually unchanged in the 15 patients with persistent
      infection. In contrast, both basal and stimulated acid secretion and gastric
      emptying time of solids remained unmodified over time in both groups of patients.
      CONCLUSIONS: We confirm that also in patients with functional dyspepsia H. pylori
      eradication in the long run significantly reduces gastrin and PGI release as a
      result of improvement in the underlying antral gastritis, but this is not
      accompanied by modifications of gastric emptying of solids or acid secretion.

PMID- 9648984
TI  - Variation in the 13C-urea breath test value by nationality in Helicobacter pylori
      infected children.
AB  - BACKGROUND: The 13C-urea breath (13C-UBT) test value is (semi-)quantitatively
      related to Helicobacter pylori density in the gastric antrum, and the value
      correlates with the grade of gastritis. The aim of this study was to assess
      variation of the 13C-urea breath test value by sociodemographic factors in H.
      pylori-positive children. METHODS: The analysis was performed on 127 asymptomatic
      children (aged 5-7 years) who were identified as H. pylori-positive with the 13C
      UBT test in a large population-based epidemiologic study in the city of Ulm
      (southern Germany). The parents of the children were asked to fill out a
      standardized questionnaire about sociodemographic data. RESULTS: Forty-two
      infected children (33.1%) were of German nationality, 47 children (37.0%) were of
      Turkish and 38 children (29.9%) were of another nationality. Turkish children had
      a significantly higher 13C-UBT value (geometric mean = 27.2%) than German
      children (16.7%) or children with another nationality (19.3%) (P < 0.001). Girls
      had a trend towards higher values than boys (P = 0.058 after adjustment for
      nationality). Body mass index, education of the parents, and prior use of
      antibiotics were unrelated to the extent of the 13C-UBT. CONCLUSIONS: This study
      identified significant variation in the extent of the 13C value by nationality
      among H. pylori-infected children. Further studies are needed to elucidate the
      causes and potential consequences of these variations.

PMID- 9648985
TI  - What is normal oesophageal motility? An ambulatory study.
AB  - BACKGROUND: Our aim was to establish normal values for wave characteristics and
      patterns in long-term ambulatory oesophageal body motility. METHODS: A pressure
      sensor was positioned in the pharynx or cricopharyngeus for swallow detection.
      Oesophageal body pressures were recorded 5, 10, and 15 cm above the lower
      oesophageal sphincter. Contraction patterns and wave characteristics from eating,
      drinking, and postprandial, fasting, and supine periods in 16 healthy subjects
      were studied. RESULTS: Contraction patterns were similar during eating and
      drinking periods or fasting and postprandial periods (P > 0.05). Wave
      characteristics during each period differed significantly in amplitude, duration,
      area under the curve, or peristaltic velocity (P < 0.05). During the eating
      period the amplitude and area under the curve were greatest, and peristaltic
      velocity was slowest compared with all other periods. CONCLUSIONS: Data from the
      eating and drinking periods or the fasting and postprandial periods can be
      combined for contraction pattern analysis but not for wave characteristic
      analysis, for which data from different periods should be analysed separately.

PMID- 9648986
TI  - Flow across the human pylorus soon after ingestion of food, studied with duplex
      sonography. Effect of glyceryl trinitrate.
AB  - BACKGROUND: By means of duplex sonography, gastric emptying can be related to
      antral motor activity. The aim of this study was to examine gastric emptying in
      relation to antral contractions during and immediately after ingestion of a
      liquid meal in healthy subjects and to study the effect of glyceryl trinitrate
      (GTN) on this early phase of gastric emptying. METHODS: Ten healthy, non-smoking
      men (median age, 36 years; range, 29-41 years) were studied twice on separate
      days, once without drug administration and once after taking a 0.5-mg sublingual
      GTN tablet 3 min before ingesting 500 ml of a meat soup (20 kcal; Toro). The
      subjects were investigated during 3 min of fasting, during 3 min of drinking the
      soup, and during the first 10 min postprandially. RESULTS: Transpyloric forward
      flow commenced on average 80 sec and 95 sec after the start of drinking the soup
      without and with GTN, respectively (P = NS). Non-contractile, pulsatile
      transpyloric flow (that is, pendulating, transpyloric flow not associated with
      antral contractions) occurred during episodes of concurrent relaxation of the
      terminal antrum, the pylorus, and the duodenal bulb. This type of flow occurred
      mainly just before the start of contractile, pulsatile transpyloric flow
      (associated with propulsive antral contractions). Initial non-contractile,
      pulsatile transpyloric flow before commencement of contractile, pulsatile
      transpyloric flow lasted longer with GTN (188 sec) than without GTN (25 sec) (P <
      0.05). Consequently, contractile, pulsatile transpyloric flow commenced later
      with GTN (302 sec) than without (102 sec) (P < 0.05). CONCLUSIONS: Non
      contractile transpyloric flow seems to be a physiologic phenomenon during the
      early phase of gastric emptying. GTN prolongs the initial phase of non
      contractile, and delays the onset of contractile, pulsatile transpyloric flow.

PMID- 9648987
TI  - Identification of coeliac disease in primary care.
AB  - BACKGROUND: Coeliac disease is common yet often undiagnosed because symptoms may
      be trivial, non-specific, or non-gastrointestinal, or because of lack of
      clinician awareness. Serum IgA-class endomysial antibodies (EmA) have high
      specificity for coeliac disease and may facilitate case-finding by clinicians
      other than gastroenterologists. We assessed the appropriateness and diagnostic
      yield of of requests for EmA by primary care general practitioners in a defined
      geographic area of Northern Ireland. METHODS: We identified patients who had EmA
      examination requests by their general practitioners during 1994-1996. Individual
      patient questionnaires were posted to the general practitioners concerned,
      seeking information on indications for testing, management after the result, and
      final diagnosis. We compared new patient diagnosis rates in two catchment areas,
      one served by a large district general hospital with, and the other by smaller
      hospitals without, a medical gastroenterology facility. RESULTS: A total of 239
      patients had coeliac profile testing by 69 of 177 general practitioners in the
      area. Data were available for 181 patients not previously known to have coeliac
      disease, of whom 20 (11%) had EmA. All EmA-positive patients were referred to
      hospital, where 19 underwent small-bowel biopsy, which confirmed coeliac disease
      in all 19. Only 7 (35%) of the 20 had diarrhoea, and there was no significant
      difference in EmA prevalence among patients tested with and without diarrhoea.
      Although the mean number of new patients (per 100,000 population annually)
      diagnosed by biopsy was 11 at the large hospital compared with 5 elsewhere, the
      numbers identified by EmA in general practice for the 2 catchment areas were
      similar (2 and 3, respectively). CONCLUSION: General practitioners have an
      important role in the identification of patients with coeliac disease,
      particularly where there is no local medical gastroenterology facility, and this
      is facilitated by EmA testing.

PMID- 9648988
TI  - Celiac disease risk in the USA: high prevalence of antiendomysium antibodies in
      healthy blood donors.
AB  - BACKGROUND: Recent epidemiologic studies in Europe using antigliadin (AGA) and
      anti-endomysium antibodies (AEA) for initial screening have shown that the
      overall prevalence of celiac disease (CD) is about 1:300. There are no comparable
      scientific data for the USA, where CD is considered rare. The main aim of this
      study was to determine the prevalence of increased AEA in healthy blood donors in
      the USA. METHODS: Sera from 2000 healthy blood donors were screened for IgG AGA
      and IgA AGA with an enzyme-linked immunosorbent assay test. All those with
      increased AGA levels, those with intermediate levels, and random samples with low
      levels were tested for AEA, using both monkey esophagus (ME) and human umbilical
      cord (HUC) cryosections as substrates. RESULTS: The mean age of the blood donors
      was 39 years, with 52% being men, 85.2% being Caucasian, 11.8% African-American,
      1.5% Asian, and 1.5% Hispanic. Eight healthy blood donors had positive AEA tests
      on both monkey esophagus and human umbilical cord. Among the eight subjects with
      increased AEA levels seven were Caucasian and one was African-American. All the
      four examined AEA-positive donors carried the known susceptibility alleles for
      CD. CONCLUSIONS: The prevalence of increased AEA levels in healthy blood donors
      in the USA is 1:250 (8:2000). This is similar to that reported in countries in
      Europe, where subsequent small-intestinal biopsies have confirmed CD in all those
      with AEA positivity. On the basis of a high positive predictive value of the AEA
      antibody test, it is likely that the eight blood donors identified in this study
      have CD. These data suggest that CD is not rare in the USA and that there is need
      for a large-scale epidemiologic study to determine the precise prevalence of the
      disease in the USA.

PMID- 9648989
TI  - Dietary intake, smoking, and transient anti-gliadin antibodies.
AB  - BACKGROUND: The detection of IgA anti-gliadin antibodies in adults can either be
      helpful in the diagnosis of coeliac disease, be persistent in subjects with
      normal jejunal mucosa, or occur transiently. We decided to investigate the
      effects of smoking, alcohol consumption, and dietary intake on the development of
      IgA anti-gliadin antibodies. METHODS: Serum samples from subjects enrolled from a
      large Northern Ireland population sample (MONICA survey) were screened for IgA
      anti-endomysium and IgA anti-gliadin antibodies. All subjects with positive
      antibodies were invited for clinical assessment 3-4 years after the initial
      screening sample. During this follow-up a repeat serum sample was obtained and a
      jejunal biopsy performed. At enrollment in the MONICA survey, lifestyle
      information including smoking, alcohol consumption, and dietary intake was
      obtained. RESULTS: At follow-up 13 subjects had persistent positive serology and
      villous atrophy, and 9 had persistent positive serology but normal jejunal
      histology; in 29 the serology had returned to normal, and the jejunal histology
      was normal There was no difference in smoking, alcohol consumption, or dietary
      intake between subjects with and without coeliac disease. Subjects with transient
      serology findings ate significantly more soda bread than the other groups (at the
      time of initial screening). Analysis of gliadin content of soda bread and plain
      white bread showed a significantly higher amount of gliadin present in soda
      bread. CONCLUSIONS: Subjects with transient IgA anti-gliadin antibodies eat
      significantly more soda bread. The gliadin content of Irish soda bread contained
      a greater amount of gliadin than white bread. Eating breads with high available
      gliadin content may cause the appearance of anti-gliadin antibody.

PMID- 9648990
TI  - Increased serum levels of vascular endothelial growth factor in patients with
      inflammatory bowel disease.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent angiogenic,
      vascular permeability-enhancing, and calcium-dependent enzyme-modulating cytokine
      with overexpression in various pathologic disorders, including granulomatous
      inflammation, tissue repair, delayed hypersensitivity reactions, rheumatoid
      arthritis, and tissue ischemia. The present study investigates the role of VEGF
      in chronic inflammatory bowel disease. METHODS: Thirty-one patients with Crohn's
      disease, 15 patients with ulcerative colitis, and 9 healthy volunteers were
      studied. VEGF serum levels were measured with a solid-phase enzyme-linked
      immunosorbent assay. RESULTS: Significantly increased VEGF serum levels were
      observed in both active Crohn's disease and active ulcerative colitis when
      compared with healthy controls. Patients with active Crohn's disease and active
      ulcerative colitis showed significantly higher VEGF serum levels than patients
      with quiescent disease. No difference was observed between inactive disease and
      healthy controls. In addition, strongly increased VEGF serum levels were found in
      patients with Crohn's disease with fistulas in the absence of clinical,
      endoscopic, histologic, and laboratory findings of disease activity. CONCLUSIONS:
      Significantly increased VEGF serum levels were observed in patients with active
      Crohn's disease and ulcerative colitis, which suggests that VEGF has an important
      role in chronic inflammatory bowel disease. Its possible association with
      fistulas has yet to be determined.

PMID- 9648991
TI  - Perinuclear anti-neutrophil cytoplasmic antibodies in ulcerative colitis after
      restorative proctocolectomy do not correlate with the presence of pouchitis.
AB  - BACKGROUND: Although perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA)
      expression is strongly associated with ulcerative colitis, its relationship with
      the occurrence of pouchitis after restorative proctocolectomy is uncertain.
      METHODS: Serum p-ANCA was assayed using both indirect immunofluorescence and
      enzyme-linked immunosorbent assay (ELISA) in 49 patients, of whom 25 had, and 24
      had not, developed pouchitis. Control sera were obtained from 15 healthy
      volunteers. RESULTS: By means of indirect immunofluorescence, p-ANCA was detected
      in 45.8% of patients without and in 48% with pouchitis (NS). Twenty-three (46.9%)
      of the 49 colitis patients were p-ANCA-positive, compared with none of the 15
      controls (P < 0.01). By means of ELISA, p-ANCA positivity was present in 50% of
      patients without and in 68% with pouchitis (NS). CONCLUSION: Whereas p-ANCA was
      associated with ulcerative colitis as compared with normal individuals, it was
      not associated with pouchitis. Thus it is unlikely to be a suitable pre-operative
      marker to identify those patients who will develop pouchitis.

PMID- 9648992
TI  - The value of methods to determine zinc deficiency in patients with Crohn's
      disease.
AB  - BACKGROUND: The serum zinc concentration is frequently applied for the assessment
      of zinc deficiency, but this concentration is also influenced by other factors.
      The aim of this study was to compare various methods of assessing the zinc status
      in patients with Crohn' s disease. METHODS: Serum levels of zinc, serum alkaline
      phosphatase activity, and zinc in various types of cells were related to factors
      potentially inducing zinc deficiency: the number of liquid stools, weight loss,
      bowel resection, and the extent and severity of inflammation. RESULTS: Thirty-one
      patients with more or less active Crohn's disease were included. In 68% of these
      patients the serum zinc concentration was less than the reference level, and it
      was correlated with the extent of bowel resection and the van Hees Index but not
      with the Crohn's Disease Activity Index. Serum alkaline phosphatase activity was
      correlated with bowel resection. Zinc in blood cells was poorly correlated with
      factors inducing zinc deficiency. CONCLUSION: A decrease of serum zinc
      concentration is frequently seen in active Crohn's disease. This study suggests
      that the determination of zinc in blood cells is not superior to the
      determination of the serum zinc concentration and serum alkaline phosphatase
      activity.

PMID- 9648993
TI  - Antineutrophil and pancreatic autoantibodies in first-degree relatives of
      patients with inflammatory bowel disease.
AB  - BACKGROUND: Perinuclear antineutrophil antibodies (P-ANCA) are found in
      ulcerative colitis, and autoantibodies against exocrine pancreas (PAB) in Crohn's
      disease. Their potential role as genetic or pathophysiologic factors is unclear.
      METHODS: In 61 patients with ulcerative colitis, 76 patients with Crohn's
      disease, 101 first-degree relatives of patients with ulcerative colitis, 105
      first-degree relatives of Crohn's disease patients, and 56 healthy unrelated
      controls autoantibodies were detected by indirect immunofluorescence. RESULTS:
      Forty-six per cent of patients with ulcerative colitis (28 of 61) and 38% of
      patients with Crohn's disease (29 of 76) were P-ANCA- and PAB-positive,
      respectively. In relatives of patients with ulcerative colitis P-ANCA were found
      in 3% (3 of 101), and in relatives of Crohn's disease patients PAB were detected
      in 4% (4 of 105), which is not significantly different from the occurrence in the
      healthy controls. CONCLUSIONS: The frequency of P-ANCA and PAB does not suggest a
      role as genetic markers for inflammatory bowel disease.

PMID- 9648994
TI  - Escherichia coli and Proteus mirabilis inhibit the perinuclear but not the
      circulating antineutrophil cytoplasmic antibody reaction.
AB  - BACKGROUND: Perinuclear antineutrophil cytoplasmic antibodies (P-ANCA) are found
      in 48%-83% of serum samples from patients with ulcerative colitis (UC). Their
      pathogenic role and initiating stimuli are unknown. In contrast to patients with
      vasculitides and ANCA reactivities, the antibodies in UC patients do not react
      with myeloperoxidase (MPO) or proteinase 3 (PR3). The aim of the present study
      was to investigate whether bacterial species of the intestinal tract and other
      sources could interfere with P-ANCA in sera from patients with UC. METHODS:
      Seventeen P-ANCA-positive and anti-MPO-negative serum samples from patients with
      UC were tested with Escherichia coli 014 and Staphylococcus aureus Wood 46. Six
      of these serum samples with different P-ANCA titres were selected to test further
      the influence of 15 different gram-negative or gram-positive bacterial strains.
      Six anti-MPO positive P-ANCA, 5 anti-PR3 positive C-ANCA, and 10 antinuclear
      antibody (ANA)-positive serum samples were used as controls. The antineutrophil
      cytoplasmic antibodies (ANCAs) were analysed by an indirect immunofluorescence
      method (IIF) on ethanol-fixed neutrophils, and the ANAs were tested by IIF on HEp
      2 cells or rat liver tissues. The bacteria used in the experiments were either
      live or killed by formalin or glutaraldehyde fixation or heated at 80 degrees C
      for 30 min. The test was first performed as a bacterial absorption test with
      sedimented organisms and then at various temperatures with the supernatant from
      suspension of live bacteria. RESULTS: Both MPO-positive and MPO-negative P-ANCA
      reactivity was abolished by absorption of patient sera with live E. coli and
      Proteus mirabilis but not with bacteria representing members of 10 other species,
      suggesting that antibody reactivity was absorbed away. However, continued
      experiments indicated that the inhibition of P-ANCA was not due to classic
      antigen-antibody interactions but rather to decomposition of the antigenic
      substrate of the neutrophils by factors present in the supernatants of live E.
      coli and P. mirabilis. The activity of the supernatant was temperature-dependent,
      with strong activity at room temperature and 37 degrees C, no activity at 0
      degrees C, and abolished by mild heat treatment (56 degrees or 60 degrees C). No
      activity was shown in the supernatants from bacteria treated with formaldehyde or
      glutaraldehyde. CONCLUSIONS: Soluble material from live E. coli and P. mirabilis
      has the capacity to decompose the antigenic substrate of neutrophils responsible
      for both MPO-positive and MPO-negative P-ANCA, most probably brought about
      through enzymatic activity. Anti PR3-positive C-ANCA were not affected, which
      suggests substrate specificity of the proposed enzymatic activity.

PMID- 9648996
TI  - Stomach leiomyosarcoma: secular trends in incidence and survival in Sweden, 1960
      1989.
AB  - BACKGROUND: This population-based study was undertaken to investigate the
      epidemiology of stomach leiomyosarcoma (GIS tumors) and to study the prognosis in
      affected patients. METHODS: The Swedish Cancer Registry was used to identify all
      incident cases of stomach leiomyosarcoma from 1960 to 1989, and the Death
      Registry and the Registry of Population Changes were used for follow-up. RESULTS:
      The age-standardized incidence in men increased from 1.0 per 10(6 ) per year in
      1960-69 to 1.8 per 10(6) per year in 1980-89. The corresponding rates in women
      were 0.6 per 10(6) and 1.2 per 10(6), respectively. The relative 5-year survival
      was 39.4% in men and 62.4% in women (P = 0.03). There was no statistically
      significant improvement in 5-year relative survival during the study period.
      CONCLUSION: The observed incidence of stomach leiomyosarcoma increased during the
      study period, most likely due to improved diagnostic accuracy. The survival of
      patients with this malignant tumor remained unchanged.

PMID- 9648995
TI  - An immunohistochemical study of bcl-2 and p53 protein expression in pancreatic
      carcinomas.
AB  - BACKGROUND: Only a few articles have examined the relationship between bcl-2
      expression and clinical findings or bcl-2 expression and p53 expression in
      pancreatic carcinomas. METHODS: We investigated bcl-2 protein and p53 protein
      expression by means of immunohistochemical methods. RESULTS: The immunostaining
      for bcl-2 was positive in 16 (20%) of 81 cases of pancreatic carcinoma. There
      were no significant correlations between bcl-2 expression and the age, gender,
      region of sampling, or clinical stage of the patients. Bcl-2 protein was detected
      more frequently in histologically high-grade pancreatic carcinomas (grade III,
      31%; grade II, 14%; grade I, 0%); however, there was no significant difference in
      prognosis between patients with and without bcl-2 protein expression.
      Immunostaining for the p53 protein was positive in 45 (56%) of 81 cases of
      pancreatic carcinoma. There was no significant correlation between bcl-2 protein
      expression and p53 protein expression. CONCLUSION: Bcl-2 was often detected in
      histologically high-grade pancreatic carcinomas, although there was no
      significant correlation between bcl-2 expression and the prognosis.

PMID- 9648997
TI  - Long-term results of percutaneous transhepatic biliary drainage for benign and
      malignant bile duct strictures.
AB  - BACKGROUND: Long-term percutaneous transhepatic biliary drainage (PTBD) is a
      valid alternative to surgery in patients with benign or malignant bile duct
      strictures in whom endoscopic drainage has failed. However, few data are
      available on the long-term outcome with percutaneous drainage, specially when the
      application of Yamakawa-type prostheses is considered. METHODS: During 1996, 48
      patients who were either treated with primary PTBD insertion followed by PTBD
      exchanges (n = 15) or who presented only for exchange of an earlier PTBD (n = 33)
      were included in the study. Thirty-one patients had malignant strictures, and 17
      had benign ones. The PTBD catheters were scheduled for exchange every 3 months or
      earlier if signs and symptoms of obstruction or other problems were present. The
      data were collected prospectively during each follow-up visit and included both
      symptoms and the status and function of the PTBD at the time of exchange.
      RESULTS: Although PTBD was highly effective in relieving jaundice (progression of
      cholestasis was observed in only 2 cases), 73 of the 157 PTBD exchanges (47%) had
      to be carried out earlier than scheduled. Premature exchange was needed for
      clinical reasons, such as fever indicating PTBD dysfunction, in only 19% of these
      cases. The other reasons were related to the PTBD catheter and consisted of bile
      leakage alongside the drain (33%), PTBD disconnection or complete dislocation
      (30%), or occlusion suspected during regular flushing of the drain (15%). In most
      cases exchanging the drain was sufficient to solve the problem; in cases of
      complete dislocation, dilation of the same tract (n = 6) or fresh puncture and
      establishment of a new drainage site (n = 2) were necessary. Reducing the PTBD
      exchange interval from 3 to 2 months would have decreased the number of premature
      stent exchanges by 26%. CONCLUSIONS: Although PTBD is an effective method of
      biliary drainage, there are frequently minor problems-mostly catheter-related
      which require premature exchange of the drain in almost half of the cases, and
      this may affect the patients' quality of life. Improvements in PTBD materials and
      catheter design are therefore needed. The effectiveness of reducing the intervals
      between PTBD exchanges should also be examined.

PMID- 9648998
TI  - Neuroticism in relation to recovery and persisting pain after laparoscopic
      cholecystectomy.
AB  - BACKGROUND: Persisting pain is seen in 20%-30% of patients after cholecystectomy
      for symptomatic gallbladder stones. The only preoperative factor that seems
      predictive is psychic vulnerability or neuroticism. Findings with regard to the
      influence of psychologic factors on recovery are contradictory, too. The aim of
      the present study was to examine a possible relationship between neuroticism and
      recovery and the outcome of operation. METHODS: Ninety-four patients who had had
      a laparoscopic cholecystectomy performed were tested psychologically with a
      Danish psychic vulnerability scale and with the Eysenck Neuroticism Scale before
      and 1 year after operation. The course of recovery was registered 1 month after
      operation, and outcome with regard to persisting pain 1 year postoperatively.
      RESULTS: No correlations were found between neuroticism scores and postoperative
      hospital stay or time to regain work/normal activities (P > 0.05). Persisting
      pain was found in 18% of the patients 1 year after operation. Although the
      patients with persisting pain had higher neuroticism scores preoperatively, the
      difference from the patients with successful outcome of the operation first
      became statistically significant 1 year postoperatively (P < 0.01-0.05).
      CONCLUSIONS: The results do not indicate that neuroticism influences the short
      recovery process after laparoscopic cholecystectomy. With regard to persisting
      pain, the higher neuroticism scores in these patients 1 year after the operation
      could be the consequence of the pain rather than aetiologic factors.

PMID- 9648999
TI  - Value of early blood Th-1 cytokine determination in predicting severity of acute
      pancreatitis.
AB  - BACKGROUND: Early evaluation of the severity of acute pancreatitis (AP) requires
      measurement of many variables within 48 h after admission. Septic complications
      (SC) are frequent, and preliminary studies have highlighted the value of
      prophylactic antibiotherapy; however, single and reliable predictive markers of
      sepsis are not yet available. The aim of this study was to assess the value of
      determining early blood Th-1 cytokines and their natural antagonists (interleukin
      6 (IL-6), IL-1, IL-1ra, and the soluble form of tumor necrosis factor (sTNF)
      receptors RI and RII) to predict the severity and SC during AP. METHODS: Thirty
      seven patients with AP were prospectively included; 25 of them had severe AP,
      including 8 with SC. Serum cytokines were measured 48 h and 72 h after the onset
      of AP with an enzyme-linked immunosorbent assay. The optimal severity or SC
      diagnostic thresholds was determined using receiver operative curves. RESULTS:
      Severe AP in accordance with the Atlanta criteria were better predicted by C
      reactive protein and IL-6 serum determination, albeit these levels could not
      predict absolutely the death of two patients. In severe AP cases (n = 25) the IL
      1 to IL-1-ra ratio was lower in cases further complicated by sepsis ((6+/-4) 10(
      3) versus (34+/-13) 10(-3), P < 0.05); moreover, sTNF RI (2497+/-270 pg/ml versus
      2133+/-611 pg/ml, P < 0.05) and RII (3751+/-400 pg/ml versus 3045+/-509 pg/ml, P
      < 0.05) were higher in AP characterized by further SC. The IL-1 to IL-1-ra ratio
      and IL-1 concentration were dramatically decreased within the first 48 h ((0.4+/
      0.4) 10(-3) versus (30+/-11) 10(-3), P < 0.05, and 0.3+/-0.3 versus 15+/-3 ng/l,
      P < 0.05) in patients with further infection of the pancreatic necrosis (n = 3).
      The SC diagnosis was better anticipated by an IL-1 to IL-1-ra ratio lower than 5
      x 10(-3) or by an sTNF RI higher than 1750 pg/ml and sTNF RII higher than 2750
      pg/ml, and the infection of the pancreatic necrosis by an IL-1 concentration <2
      ng/l or an IL-1 to IL-1-ra ratio <2 x 10(-3). CONCLUSION: Besides severity
      markers, IL-1, IL-1-ra, and sTNF RI and RII should be considered in base-line AP
      assays and, if confirmed by larger studies, could help to screen patients at risk
      for SC and candidates for prophylactic antibiotherapy with a good negative
      predictive value.

PMID- 9649000
TI  - Reflections on Crohn's disease and healing.
AB  - One patient's story is recounted. Relatively asymptomatic for 20 years, the
      patient reflects on factors that contributed to his healing. Psychosocial and
      spiritual dimensions are described as well as biomedical aspects. The story
      concludes that dealing with Crohn's disease triggered a spiritual quest which in
      turn contributed to the patient's healing.

PMID- 9649001
TI  - Hot water swallows improve symptoms and accelerate esophageal clearance in
      esophageal motility disorders.
AB  - Cold liquid ingestion may precipitate episodes of dysphagia and chest pain in
      patients with spastic esophageal motility disorders. The effect of hot liquids on
      esophageal symptoms, esophageal peristalsis, and clearance and any potential
      therapeutic benefit in such patients has not been examined. Using esophageal
      scintigraphy and manometry, we have investigated the effects of hot water
      swallows on dysphagia, chest pain, and esophageal motility and clearance in
      patients with esophageal motility disorders. We studied 48 men and women with
      intermittent dysphagia to both solids and liquids, chest pain, and/or
      regurgitation. All patients underwent upper endoscopy, barium swallow, and
      esophageal manometry using standard techniques. Esophageal scintigraphy assessed
      esophageal transit time (ETT) and retrograde intraesophageal movement of bolus at
      baseline (22 degrees C) and after hot (60 degrees C) water swallows. Esophageal
      manometry assessed the amplitude and duration of esophageal contractions in
      response to baseline and hot water swallows. Patients were followed clinically
      for as long as 6 months to assess symptomatic response. We found that baseline
      esophageal scintigraphy revealed a mean ETT of 48.5 seconds; after hot water
      swallow, mean ETT was 27.8 seconds (p < 0.001). The number of secondary peaks at
      baseline was 3.5; after hot water swallow, it was 2.1 (p < 0.001). Baseline
      esophageal manometry showed a mean esophageal body contraction amplitude of 188
      mm Hg (mean duration, 11.8 seconds) in response to wet swallows and 125 mm Hg
      (mean duration, 5.7 seconds) with hot water swallows (p < 0.001). Clinically, 28
      (58%) of 48 patients noted significant (>50%) improvement of their symptoms and
      have been ingesting hot water or other hot liquids regularly with their meals. We
      conclude that hot water accelerates esophageal clearance, decreases the amplitude
      and duration of esophageal body contractions, and improves symptoms in patients
      with esophageal motility disorders. Because of its safety and simplicity, it may
      have an important role in the management of these chronic conditions.

PMID- 9649002
TI  - Pulmonary nodules in patients with esophageal carcinoma.
AB  - The clinical significance of lung nodules in patients with esophageal carcinoma
      has received little attention. Therefore, we carried out a retrospective detailed
      review of 116 consecutive cases of esophageal carcinoma, including 98 squamous
      cell cancers, seen at the Philadelphia Veterans Affairs Medical Center between
      1984 and 1997. Seventy-four percent of our patients were black; it was not
      surprising therefore that 84% of our patients in this series had squamous cell
      cancers. Initially, chest radiographs, computed tomography (CT) scans, or
      thoracotomy showed solitary pulmonary nodules in 22 (19%) patients. A definitive
      diagnosis was established in 19 patients, including 15 (68%) benign nodules and 4
      (18%) new primary lung carcinomas. Three (14%) nodules were indeterminate, but in
      no case could a solitary lung metastasis be identified. Radiographic evidence of
      multiple lung metastases was present, however, in 4 (3%) of 116 patients at
      diagnosis. Autopsies of six patients were later performed, and three showed
      multiple lung metastases; two of these patients had negative chest radiographs
      shortly before death. Our experience suggests that for a cohort of mostly
      squamous cell esophageal cancers, a solitary lung metastasis is rare at
      diagnosis; a solitary pulmonary nodule at this time likely represents a benign
      abnormality or primary lung cancer. Multiple pulmonary metastases are also very
      unusual at diagnosis, probably become increasingly common during the terminal
      phases of disease, and may be radiographically occult.

PMID- 9649003
TI  - In vivo comparison of esophageal varices at and above the diaphragmatic high
      pressure zone using high resolution endoluminal sonography.
AB  - Our objective in this study was to use high resolution endoluminal sonography to
      compare the size of esophageal varices within 5 cm of and at the esophageal high
      pressure zone. We carried out the study in 36 patients with endoscopically proven
      esophageal varices. A 20-MHz 6.2F ultrasound catheter was passed through a 34F
      endoscope and used to image esophageal varices as it was slowly withdrawn through
      the high pressure zone (the level at which the diaphragm was imaged) and into the
      body of the esophagus approximately 5 cm above the high pressure zone. All images
      were captured on videotape and reviewed by one of the investigators. The mean,
      total, and percent cross-sectional surface areas occupied by varices were
      calculated and then compared within 5 cm and at the esophageal high pressure
      zone. Six of 36 (17%) patients had no varices imaged at the high pressure zone
      but did have varices imaged in the distal esophagus. The mean cross-sectional
      surface area per varix at the high pressure zone (0.036+/-0.006 cm2) was
      significantly less (p < or = 0.0001) than the mean cross-sectional area per varix
      5 cm above the high pressure zone (0.142+/-0.018 cm2). The average total cross
      sectional surface area occupied by varices at the high pressure zone (0.137+/
      0.034 cm2) was significantly less (p < 0.0001) than the average cross-sectional
      surface area occupied by varices 5 cm above the high pressure zone (0.672+/-0.080
      cm2). The mean percent esophageal wall cross-sectional surface area occupied by
      varices at the high pressure zone (16%) was significantly less (p < or = 0.0001)
      than 5 cm above the high pressure zone (49%). We conclude that the mean, total,
      and percent cross-sectional surface areas of esophageal varices at the high
      pressure zone are significantly less than those 5 cm above the high pressure
      zone.

PMID- 9649004
TI  - Factors affecting patient tolerance of upper gastrointestinal endoscopy.
AB  - Doctors are optimistic in their perception of how acceptable endoscopy is for
      patients. We analyzed elements that contribute to a poor experience for the
      patient and the agreement between the perceptions of endoscopists and patients.
      Eighty-four out-patients who had undergone gastroscopy completed questionnaires
      (response rate of 73%) 48 to 96 hours after the procedure. The endoscopist
      completed a similar questionnaire. Questions concerned overall tolerance,
      swallowing, retching and vomiting, sedation, duration, diagnosis, age, and sex.
      Data from both doctor and patient were available in 84 cases. The type of
      sedation, administration of hyoscine or Xylocaine (Astra Pharmaceuticals Ltd.,
      Kings Langley, UK), diagnosis, and expression of need for more sedation were not
      statistically significantly related to the overall patient score. The largest
      contribution to a poor overall tolerance score arose from difficulty in
      swallowing the endoscope, followed by the duration of the procedure. A total of
      8.3% of patients reported some overall difficulty which was not recognized by the
      endoscopist. In relation to retching and vomiting, 11.9% of patients had
      difficulty with retching and vomiting, which went unrecognized by the doctor, and
      18% had difficulty in swallowing the endoscope. There was fair agreement between
      the assessments of overall acceptability of both endoscopists and patients.
      Difficulty in intubation, however, is the major contributor to a poor tolerance
      of gastroscopy and also the issue on which doctors and patients disagreed the
      most.

PMID- 9649005
TI  - Ambience in the endoscopy room has little effect on patients.
AB  - With hopes of alleviating discomfort and improving the tolerance of patients
      undergoing endoscopy, we have assessed the influence of various background
      conditions in the endoscopy room. Two hundred twenty-one candidates for upper
      endoscopy were randomly allocated to four groups, each with one of the following
      conditions in the endoscopy room: background music and conversation related to
      the patient's complaints (n=50); background music and conversation unrelated to
      the patient (n=53); background music only, with the staff maintaining silence
      (n=49); and complete silence (n=47). Before endoscopy patients answered a 26-item
      questionnaire that included an evaluation of their degree of anxiety before the
      examination. Conscious sedation was induced by using 3 mg midazolam. After
      complete recovery from sedation, patients answered another set of questions.
      Patients in all four groups felt quite comfortable with the atmosphere in which
      gastroscopy was performed. Neither music, conversation, nor silence had a great
      effect on patients as far as improving tolerance or diminishing anxiety.
      Therefore, endoscopists and nurses may have a free hand in choosing the
      prevailing conditions during the examination. This conclusion may be valid for
      both patients and the staff involved in other invasive procedures performed under
      light sedation.

PMID- 9649006
TI  - Helicobacter pylori infection is markedly increased in patients with autoimmune
      atrophic thyroiditis.
AB  - Infection by viral or bacterial pathogens has been suspected in playing a role in
      the development of autoimmune thyroid disease. Because Helicobacter pylori might
      be involved in the development of nongastrointestinal conditions such as rosacea,
      ischemic heart disease, and diabetes mellitus, we evaluated the prevalence of H.
      pylori infection in patients with autoimmune thyroid disease. Fifty-nine patients
      with autoimmune thyroid disease were included: autoimmune atrophic thyroiditis
      (n=21), Hashimoto's thyroiditis (n=18), and Graves' disease (n=20). Twenty
      patients with nontoxic multinodular goiter served as controls for nonautoimmune
      thyroid disease, and 11 patients with Addison's disease served as controls for
      nonthyroid endocrine autoimmune disease. The levels of anti-H. pylori
      immunoglobulin G (IgG) were determined, and a radiolabeled urea breath test were
      performed. The prevalence of H. pylori infection was markedly increased in the
      patients with autoimmune atrophic thyroiditis (85.7%), compared with the controls
      with nontoxic multinodular goiter (40%) and Addison's disease (45.4%). Infection
      by H. pylori resulted in increased levels of gastrin, pepsinogen I, and
      pepsinogen II in the H. pylori-positive groups, compared with the H. pylori
      negative groups. A positive linear regression was found between the levels of
      microsomal autoantibodies and those of anti-H. pylori IgG in patients with
      autoimmune atrophic thyroiditis (n=21; r=0.79; p < 0.01). Finally, and although
      the overall prevalence of H. pylori infection was not increased, the anti-H.
      pylori IgG levels and the results from the breath test were higher in the
      patients with Graves' disease and Hashimoto's thyroiditis patients than in the
      controls. Clearly, the prevalence of H. pylori infection is increased in
      autoimmune atrophic thyroiditis and results in abnormalities of gastric secretory
      function. The strong relation between the levels of anti-H. pylori IgG and the
      levels of microsomal antibodies suggests that H. pylori antigens might be
      involved in the development of autoimmune atrophic thyroiditis or that autoimmune
      function in autoimmune atrophic thyroiditis may increase the likelihood of H.
      pylori infection.

PMID- 9649007
TI  - A simplified urea breath test for the diagnosis of Helicobacter pylori infection
      using the LARA System. Laser Assisted Ratio Analyzer.
AB  - Helicobacter pylori, one of the most prevalent human pathogens, is associated
      with chronic gastritis, peptic ulcer disease, and possibly gastric cancer and
      primary gastric lymphoma. The need to treat these patients has necessitated the
      development of improved methods to diagnose H. pylori infection. We present the
      preliminary assessment of a 13C-urea breath test (UBT) in which the expired 13CO2
      is detected in a rapid, simple, inexpensive way by the LARA (Laser Assisted Ratio
      Analyzer) System (Alimenterics, Inc., Morris Plains, NJ). Eighty-seven
      consecutive patients, examined for upper gastrointestinal symptoms, underwent
      endoscopy. H. pylori infection was established by antral biopsies and a rapid
      urease test (CLOtest). The UBT was performed between 2 and 24 hours after
      endoscopy. Of the 84 analyzable patients, 70 were found to be H. pylori-positive
      either by histology or by CLOtest. All 70 were positive by the LARA UBT, yielding
      a sensitivity of 100%. Fourteen patients were negative for H. pylori by histology
      and the CLOtest. Of these, 12 were negative by the LARA UBT and 2 were positive,
      yielding a specificity of 85.7%; because of the limitations of H. pylori
      detection by histology or urease assays, however, the specificity of the UBT may
      have been underestimated. Our study demonstrates the feasibility of a
      nonradioactive, rapid UBT based on the LARA system and suggests the need for its
      more detailed evaluation.

PMID- 9649008
TI  - Premedication with Xylocaine spray does not lead to a false positive rapid urease
      test.
AB  - Rapid urease tests are used for quick identification of Helicobacter pylori
      during upper gastrointestinal endoscopy. Rapid urease test solutions contain
      urea, which in the presence of H. pylori urease, generates ammonia, which changes
      the test medium color to indicate a positive result. Theoretically, Xylocaine
      spray (ASTRA, Sodertalje, Sweden), which has a basic pH value, could cause a
      similar positive reaction in the test medium. To determine whether patients
      premedicated with Xylocaine spray have a higher rate of false positive urease
      tests, we compared the results of a rapid urease test and histologic stains in
      107 patients, 54 premedicated with Xylocaine spray and 53 premedicated with
      intravenous midazolam but not Xylocaine spray. There were no significant
      differences in test sensitivity, specificity, or predictive values between the
      study groups. We conclude that patients can be premedicated with Xylocaine spray
      without concern that the false positive rate of rapid urease tests will increase.

PMID- 9649009
TI  - Postoperative chemotherapy may improve prognosis in unresectable gastric cancer.
AB  - We have retrospectively evaluated to prognosis of patients with unresectable
      gastric cancer (UGC) and the effect of postoperative chemotherapy on that
      prognosis. One hundred patients who died of UGC included 37 patients who received
      postoperative chemotherapy (chemotherapy group) and 63 patients who did not
      receive postoperative chemotherapy (control group). Chemotherapy regimens were as
      follows: intravenous mitomycin (MMC) plus 5-fluorouracil (5-FU) (n=15), oral 5-FU
      alone (n=10), intravenous methotrexate (MTX) plus 5-FU (n=8), intravenous
      cisplatin plus 5-FU (n=2), and hepatic arterial infusion of 5-FU plus oral 5-FU
      (n=2). No prior chemotherapy or radiation therapy was given. All patients'
      cancers were stage IV. Median survival of the chemotherapy group (238 days) was
      significantly longer than the control group (137 days). The 1-year survival rate
      in the treated group was 19.0% but only 2.4% in the control group (p < 0.01).
      Patients with palliative gastrojejunostomy did not survive significantly longer
      than those having laparotomy alone or ileal tube insertion. We conclude that the
      prognosis for patients with UGC remains very poor, but postoperative chemotherapy
      may contribute to prolonged survival in patients with UGC.

PMID- 9649010
TI  - Relatively low expression of multidrug resistance-1 (MDR-1) and its possible
      clinical implication in gastric cancers.
AB  - The mechanism of drug resistance of gastric cancer cells has rarely been
      investigated. We specifically examine the magnitude and the biologic significance
      of multidrug resistance-1 (MDR-1) expression in human gastric cancer. All
      patients had previously been treated in prospective clinical trials for advanced
      gastric cancer in our institution. Patients with adequate prechemotherapy gastric
      cancer tissues for immunohistochemical studies by a C219 monoclonal antibody were
      selected for the determination of the expression rate of MDR-1. The results were
      designated as negative or positive by the independent interpretation of two
      pathologists. A subgroup of patients who had been treated with doxorubicin- or
      etoposide-containing regimens were selected for further correlation with drug
      sensitivity. Between 1990 and 1996, a total of 60 patients, 38 men and 22 women
      with a median age of 55 years, were studied. Eight (13.3%; 95% confidence
      interval, 6%-25%) of them had MDR-1 expression. None of the pertinent
      clinicopathologic features, including the histopathologic types of the tumors and
      the extent of the diseases, correlated with the expression of MDR-1. Among the 30
      patients who had received doxorubicin- or etoposide-containing combination
      chemotherapy, 3 (10%; 95% confidence interval, 3%-27%) were designated positive
      for MDR-1 expression. None of the 3 patients responded to chemotherapy, whereas
      19 (70.4%) of the 27 patients who had not expressed MDR-1 did respond (p=0.041 by
      Fisher's exact test). We conclude that the expression of MDR-1 in gastric cancer
      is relatively low. Its expression, however, is clinically relevant and is useful
      in predicting the chemoresistance of patients with gastric cancer receiving
      doxorubicin- or etoposide-containing combination chemotherapy.

PMID- 9649011
TI  - Colonoscopy without sedation.
AB  - Colonoscopy is routinely performed with conscious sedation. We wanted to
      determine if colonoscopy can be successfully completed without sedation and to
      assess patient tolerance and acceptance. One hundred nine consecutive patients
      undergoing colonoscopy were examined. The risks and benefits of colonoscopy with
      or without sedation were explained in a standard format. Patients were then given
      the option of having colonoscopy without premedication. After the procedure, as
      well as 2 to 5 days later, patients rated on an analog scale (0, no pain; 5,
      severe) the severity of pain and willingness to undergo colonoscopy in the future
      without sedation. Eighty patients underwent colonoscopy without prior sedation.
      Only 6% (n=5) required sedation to complete the examination. When questioned, 5%
      experienced no pain, 41% slight or mild pain, 34% moderate pain, and 20% severe
      pain. Seventy-three percent (n=58) were willing to undergo repeat colonoscopy
      without sedation, 10% (n=8) were undecided, and 18% (n=14) would request
      sedation. Pain severity was a strong predictor (p=0.001) of future sedation
      preference. Colonoscopy without sedation may be completed successfully in most
      patients and does not undermine many patients' willingness to undergo a similar
      procedure in the future. Sedation by choice is more cost-effective, may be safer,
      and should be offered as an alternative to routine intravenous sedation.

PMID- 9649012
TI  - Alterations in colonic anatomy induced by chronic stimulant laxatives: the
      cathartic colon revisited.
AB  - Cathartic colon is a historic term for the anatomic alteration of the colon
      secondary to chronic stimulant laxative use. Because some have questioned whether
      this is a real entity, we investigated changes occurring on barium enema in
      patients ingesting stimulant laxatives. Our study consisted of two parts. In part
      1, a retrospective review of consecutive barium enemas performed on two groups of
      patients with chronic constipation (group 1, stimulant laxative use [n=29]; group
      2, no stimulant laxative use [n=26]) was presented to a radiologist who was
      blinded to the patient group. A data sheet containing classic descriptions of
      cathartic colon was completed for each study. Chronic stimulant laxative use was
      defined as stimulant laxative ingestion more than three times per week for 1 year
      or longer. To confirm the findings of the retrospective study, 18 consecutive
      patients who were chronic stimulant laxative users underwent barium enema
      examination, and data sheets for cathartic colon were completed by another
      radiologist (part 2). Colonic redundancy (group 1, 34.5%; group 2, 19.2%) and
      dilatation (group 1, 44.8%; group 2, 23.1%) were frequent radiographic findings
      in both patient groups and were not significantly different in the two groups.
      Loss of haustral folds, however, was a common finding in group 1 (27.6%) but was
      not seen in group 2 (p < 0.005). Loss of haustral markings occurred in 15 (40.5%)
      of the total stimulant laxative users in the two parts of the study and was seen
      in the left colon of 6 (40%) patients, in the right colon of 2 (13.3%) patients,
      in the transverse colon of 5 (33.3%) patients, and in the entire colon of 2
      (13.3%) patients. Loss of haustra was seen in patients chronically ingesting
      bisacodyl, phenolpthalein, senna, and casanthranol. We conclude that long-term
      stimulant laxative use results in anatomic changes in the colon characterized by
      loss of haustral folds, a finding that suggests neuronal injury or damage to
      colonic longitudinal musculature caused by these agents.

PMID- 9649014
TI  - Abnormal liver test results in myotonic dystrophy.
AB  - Myotonic dystrophy (DM) is an autosomal dominant multisystem disorder. Little
      evidence suggests the existence of liver damage in a small number of patients. We
      have prospectively evaluated liver and gallbladder function in 53 patients with
      DM in relation to clinical and genetic parameters. None of the patients had an
      enlarged liver, signs of cirrhosis, or portal hypertension. All were free of
      medication, and none were pregnant or had a history of alcohol abuse. In 35 (66%)
      patients, serum activity of at least one of six liver enzymes assayed was
      abnormal. An elevated level of alkaline phosphatase was found in 50.9%, of gamma
      glutamyltransferase in 52.8%, of 5' nucleotidase in 43.4%, of serum aspartate
      aminotransferase in 35.8%, of serum alanine aminotransferase in 33.9%, and of
      lactate dehydrogenase in 37.7%. Liver function test results did not correlate
      with severity of muscle weakness, disease duration, or serum levels of creatine
      kinase, glucose, or lipids. Motility of gallbladder and abdominal ultrasonography
      were normal. Cytosine-thymidine-guanine repeat expansion by southern blot did not
      correlate with liver enzyme abnormalities. We conclude that elevation of liver
      enzymes is frequent in DM and should be included as an additional laboratory
      finding of the disease.

PMID- 9649013
TI  - A combination therapy with simvastatin and ursodeoxycholic acid is more effective
      for cholesterol gallstone dissolution than is ursodeoxycholic acid monotherapy.
AB  - Inhibitors of 3-hydroxy,3-methylglutaryl coenzyme A (HMG-CoA) reductase have been
      reported to decrease the cholesterol saturation index (CSI) in duodenal bile in
      humans and to prevent formation of cholesterol gallstones in animal studies. We
      performed a prospective study to evaluate the role of HMG-CoA reductase
      inhibitors as gallstone-dissolving agents. Fifty patients with radiolucent
      gallstones in a gallbladder opacifying at drip infusion cholecystography were
      treated with either 10 mg/day simvastatin plus 600 mg/day ursodeoxycholic acid
      (group 1, n=26) or 600 mg/day ursodeoxycholic acid alone (group 2, n=24) for 12
      months. The ratio of solitary to multiple gallstone cases was 21:29. Plasma lipid
      levels were assessed and ultrasonographic examination of the gallbladder was
      performed at baseline and at 3-month intervals during treatment. Duodenal bile
      sampling was performed in five patients in each group at baseline and after 12
      months of treatment. Plasma cholesterol decreased significantly in group 1 but
      not in group 2. In solitary gallstone cases, no significant difference in
      dissolution rates was observed between groups 1 (3 of 9, 33%) and 2 (4 of 12,
      33%). In contrast, the dissolution rate in multiple gallstone cases was
      significantly higher in group 1 (12 of 17, 71%) than in group 2 (3 of 12, 25%) (p
      < 0.01). Bile cholesterol saturation index was significantly decreased (p < 0.01)
      but did not significantly differ between the two groups. These results suggest
      that combination therapy with simvastatin and ursodeoxycholic acid is more
      effective for cholesterol gallstone dissolution than ursodeoxycholic acid
      monotherapy in patients with multiple gallstones.

PMID- 9649015
TI  - Influence of pretreatment lesions on histologic response to interferon therapy in
      chronic hepatitis C.
AB  - We have assessed the predictive value of the grade of pretreatment liver lesions
      on histologic response to interferon therapy in patients with chronic hepatitis
      C. In 93 patients with chronic hepatitis C virus (HCV) infection who showed an
      initial response to interferon therapy, HCV RNA load and serum aminotransferase
      levels together with grade of liver histologic lesions were assessed at baseline
      and 6 months after treatment cessation. Regression of portal and periportal
      necroinflammation was observed only in sustained responders (normalization of
      aminotransferase levels and HCV RNA clearance). Neither short-term response nor
      the absence of virus was associated with significant histologic changes in the
      liver biopsies. Logistic regression analysis showed that pretreatment histologic
      lesion was an independent predictive factor of biologic response in the
      histologic regression of lesions 6 months after cessation of interferon
      treatment. In conclusion, a dense inflammatory necrotic activity is a positive
      predictor of histologic response in interferon-treated patients with HCV.

PMID- 9649016
TI  - Chronic diarrhea--induced by celiac plexus block?
AB  - A 59-year-old man had severe chronic diarrhea after a celiac plexus block. The
      block was performed because of unbearable abdominal pain caused by a benign cyst
      in the lesser sac. The patient also had diabetes mellitus and was treated with
      metformin. Thorough investigation and various therapeutic trials failed to detect
      the cause for the diarrhea or to improve it. Based on the temporal relationship
      we wonder whether the diarrhea was induced by the celiac block procedure. The
      relevant literature is reviewed.

PMID- 9649017
TI  - Idiopathic portal hypertension and angiosarcoma associated with arsenical salts
      therapy.
AB  - We describe a 60-year-old man with idiopathic portal hypertension and hepatic
      angiosarcoma. The patient had taken an arsenical preparation for the treatment of
      psoriasis for 10 years. Five cases of this association have been reported
      previously; in one only, exposure to arsenical salts was present.

PMID- 9649018
TI  - Serious hemorrhage complicating diagnostic abdominal paracentesis.
AB  - We describe two patients awaiting orthoptic liver transplantation in whom
      diagnostic paracentesis for the diagnosis of spontaneous bacterial peritonitis
      led to major hemorrhage. Accordingly, we advise caution in patients such as ours,
      particularly if the prothrombin time or partial thromboplastin time is more than
      twice the control value.

PMID- 9649019
TI  - Cystic lymphangioma of the spleen mimicking hydatid disease.
AB  - Cystic lymphangioma is a very rare condition generally accepted to be the result
      of a developmental malformation of the lymphatic system. Usually seen in
      children, it occurs infrequently in adults. The neck (75%) and axillary regions
      (20%) are the most common locations of lymphangioma, but it can occur in the
      retroperitoneum, mediastinum, mesentery, omentum, colon, pelvis, groin, bone,
      skin, scrotum, and spleen. We present a cystic lymphangioma of the spleen with
      emphasis on its rarity in this site and problems of differential diagnosis with
      hydatid disease.

PMID- 9649020
TI  - Meta-analysis of antisecretory and gastrokinetic compounds in functional
      dyspepsia.
AB  - In view of therapeutic advances, we carried out meta-analysis of results from 18
      randomized, controlled clinical studies to update a previous meta-analysis and to
      provide an overview of clinical trials involving treatment of functional
      dyspepsia. The studies were included only if they satisfied inclusion and
      exclusion criteria and assessed treatment of functional dyspepsia with the
      antisecretory compounds cimetidine and ranitidine and the gastrokinetic compounds
      cisapride and domperidone. Outcomes of each of these trials were classified in
      terms of differences in therapeutic success between active treatment and placebo.
      For antisecretory treatments, the 95% confidence intervals for the difference in
      therapeutic success between active treatment and placebo were inconsistent for
      cimetidine, but analysis of both ranitidine trials gave favorable results. For
      the gastrokinetic compounds cisapride and domperidone, the differences in success
      rates were generally higher and more in favor of active treatment than placebo.
      By combining the results from both antisecretory treatments and comparing them
      with the combined results for gastrokinetic compounds, we observed that
      gastrokinetic compounds had a greater difference in success rates than did
      antisecretory agents. Overall, our meta-analysis shows that antisecretory
      treatment with cimetidine or ranitidine offers little advantage over placebo,
      whereas gastrokinetic treatment with cisapride or domperidone is significantly
      better than placebo for treatment of functional dyspepsia.

PMID- 9649021
TI  - The chewable barium tablet slow tracking of oral and pharyngeal swallowing
      dysfunction.
AB  - Dysphagia can be due to oral or pharyngeal dysfunction as well as to esophageal
      causes. Oral and pharyngeal disturbances, however, are more common in older
      people because of their attendant risks of laryngeal, tracheal, and pulmonary
      aspiration. To guide any dietary prescriptions it is important to establish
      whether the patient can best tolerate liquids, soft foods, solid chewable
      boluses, all, or none of these. It therefore becomes important to supplement
      liquid barium swallowing studies with soft and chewable boluses mixed with
      barium. Here I describe the novel introduction of chewable barium tablets in
      conjunction with routine swallowing studies. Chewable barium tablets, if used
      properly, are safe, supply needed information, and can shorten the evaluation of
      oral and pharyngeal dysfunction studies. Because of the granular appearance of
      the tablets, aspiration due to this solid chewable bolus can be distinguished
      from liquid aspiration. Moreover, if the barium tablets are swallowed whole, they
      can help delineate esophageal strictures if the oral and pharyngeal phases of
      swallowing are normal.

PMID- 9649022
TI  - The histopathology and biologic prognostic factors of Barrett's esophagus: a
      review.
AB  - In Barrett's esophagus, stratified squamous mucosa of the lower third of the
      esophagus is replaced by columnar mucosa, as a complication of chronic
      gastroesophageal reflux. The presence of Barrett's esophagus appears to be a
      major factor in the progression to adenocarcinoma of the lower third of the
      esophagus. Therefore it is crucial to identify the subset of patients at risk for
      the development of adenocarcinoma. Dysplasia is an important histologic feature
      to evaluate because it identifies those patients who require follow-up. The
      diagnosis of biopsies with lesser degrees of abnormalities, however, makes
      microscopic evaluation less helpful in identifying patients who need more
      frequent endoscopic biopsy surveillance. DNA ploidy and the use of monoclonal
      antibodies, such as suppressor gene product p53, oncogene cerbB-2, and Ki-67,
      have added dramatically to our understanding of the biology of Barrett's
      metaplasia and have given us objective indicators to predict the presence of an
      increased risk of developing cancer.

PMID- 9649023
TI  - Extreme right lobar atrophy of the liver: a rare complication of autoimmune
      hepatitis.
AB  - Lobar atrophy is a rare morphologic change of the liver. We describe a 73-year
      old woman with mild liver dysfunction and history of Sjogren's syndrome who had
      right hepatic lobar atrophy. Serum biochemistry levels were as follows: albumin,
      4.5 g/dl; total bilirubin, 1.0 mg/dl; alanine aminotransferase, 25 international
      units/l; aspartate aminotransferase, 27 international units/l; alkaline
      phosphatase, 333 international units/l; and gamma-glutamyl transpeptidase, 332
      international units/l. Serological data were as follows: rheumatoid factor, 27.9;
      anti-nuclear antibody, 1:640; and antismooth muscle antibody, 1:80. Viral markers
      for hepatitis B were all negative. Anti-hepatitis C virus (anti-c-100) was
      negative. Portal hypertension developed thereafter, and the patient died of
      hepatic failure at age 76. Postmortem examination revealed autoimmune hepatitis
      with moderate fibrosis, portal vein thrombus, and complete obstruction of the
      right hepatic duct due to hepatolithiasis. Terminal hepatic failure resulted from
      combination of decreased hepatic volume due to the right lobar atrophy,
      exacerbation of autoimmune hepatitis in the remnant left hepatic lobe, decreased
      portal venous blood flow due to thrombosis, portal hypertension, and cholangitis
      with hepatolithiasis. This is the first reported case of hepatic lobar atrophy
      due to autoimmune hepatitis. From a clinical standpoint, patients with hepatic
      lobar atrophy, even if asymptomatic, should be followed up with careful attention
      to progression of liver diseases, portal hypertension, and biliary complications.

PMID- 9649024
TI  - Enteropathy-associated T cell lymphoma with brain involvement.
AB  - In a patient with enteropathy-associated T cell lymphoma. there was dissemination
      to the brain manifesting as an inflammatory lesion. the intestinal and brain
      lesions were studied using routine histology, immunohistochemistry, and
      polymerase chain reaction. The jejunum was involved by a multifocal large cell
      lymphoma associated with multiple inflammatory ulcers and villous atrophy with
      crypt hyperplasia of the intervening mucosa. The lesion in the brain consisted of
      necrotic tissue associated with an infiltrate of histiocytes and a relatively
      scant infiltrate of primarily small lymphocytes. The appearance was that of an
      inflammatory rather than a neoplastic process. The intestinal lymphoma cells were
      positive for T cell markers and contained cytotoxic granules detected with the
      TIA-1 monoclonal antibody. The small lymphocytes and occasional large cells in
      the cerebral lesion showed the same immunophenotype. DNA extracted from the
      intestinal lymphoma and the cerebral lesion showed identical monoclonal
      rearrangement of the TCR-gamma gene. Dissemination from enteropathy-associated T
      cell lymphoma may masquerade as an inflammatory lesion. Molecular analysis is
      useful in confirming the diagnosis.

PMID- 9649025
TI  - Telephone callback is unnecessary after outpatient endoscopy.

PMID- 9649026
TI  - Nonsteroidal anti-inflammatory drugs and gastrocolic fistula.

PMID- 9649027
TI  - Unsuccessful octreotide treatment of the watermelon stomach.

PMID- 9649028
TI  - Colon cancer after Bowen's disease.

PMID- 9649029
TI  - Colonic metastasis of a lung carcinoma with ileocolic fistula.

PMID- 9649030
TI  - Endosonographic probe-guided endoscopic resection of focal lymphoid hyperplasia
      of the rectum.

PMID- 9649031
TI  - Intramural duodenal hematoma due to pancreatitis.

PMID- 9649032
TI  - Two patients with portal vein thrombosis from lupus anticoagulant.

PMID- 9649033
TI  - Mixed adenocarcinoid tumor and Crohn's disease.

PMID- 9649034
TI  - Amebic abscess of the caudate lobe with spontaneous rupture into the biliary
      tract.

PMID- 9649035
TI  - Duodenal stenosis does regress after eradication of Helicobacter pylori!

PMID- 9649036
TI  - Short-segment Barrett's esophagus.

PMID- 9649037
TI  - Totally laparoscopic aortobifemoral bypass: a review of 10 patients.
AB  - The main purpose of this study is to evaluate the feasibility of totally
      laparoscopic aortobifemoral bypass for occlusive aortoiliac disease. Ten patients
      who had incapacitating claudication have been included to date in this
      investigation. We have designed a transabdominal retroperitoneal technique that
      allows performance of the procedure without the problems associated with
      retraction of intraperitoneal organs. During the study, surgery time decreased
      from 510 to 245 min. Mean total aortic clamping time was 121 min, and the mean
      time required to perform the aortic anastomosis was 66 min. Mean blood loss was
      820 ml. Three patients needed conversion. Postoperative complications developed
      in three patients. One had an aortoureteral fistula, which needed reoperation;
      one experienced complications related to a retroaortic left renal vein; and the
      third had a mild compartment syndrome of the right leg. Totally laparoscopic
      aortobifemoral bypass is feasible. Laparoscopic aortobifemoral bypass appears to
      ease the patient's postoperative course and could become in the not so distant
      future part of the repertoire of the surgeon performing vascular surgery.

PMID- 9649038
TI  - Technical aspects of minimally invasive abdominal surgery performed with
      needlescopic instruments.
AB  - Interest has grown in reducing the size of laparoscopic instruments. We define as
      "needlescopic" those instruments that have a diameter of < or =3 mm. We compared
      data from 60 needlescopic cholecystectomies with a matched group of laparoscopic
      procedures. No intraoperative complications occurred in either group. Operative
      time was 20% longer for the needlescopic operations. Hospital stay was similar
      for both groups. Postoperative analgesia requirements for the needlescopic group
      were 70% lower than for the laparoscopic group. From a scale (0, no scar visible,
      to 10, worst scar), patients scored their scars as 1 for the needlescopic cases
      and 5 for the laparoscopic group. Likewise, we have used needlescopic instruments
      to perform appendectomy, inguinal herniorrhaphy, adrenalectomy, splenectomy, and
      fundoplication. In conclusion, needlescopic procedures are safe and efficient.
      While they result in longer operative times, they decrease the need for
      postoperative analgesia, which may shorten convalescence and improve the cosmetic
      result.

PMID- 9649039
TI  - Hand-assisted laparoscopic distal pancreatectomy for pancreatic cystadenoma.
AB  - A cystic lesion in the body of the pancreas was detected during staging workup of
      a 59-year-old woman with T-cell lymphoma of the tongue. After six cycles of
      chemotherapy the pancreatic lesion was unchanged. Suggestive ulceration of the
      vulva with edema appeared at the end of chemotherapy. After right vulvar
      excision, distal pancreatic resection with splenectomy was carried out by a hand
      assisted laparoscopic technique utilizing a small muscle-splitting right lower
      quadrant incision. This allowed for palpation of the peritoneal cavity for
      evidence of tumor and allowed for safe and expeditious pancreatectomy. The
      pancreatic tumor was found to be a serous cystadenoma without evidence of
      malignancy. T-cell lymphoma was identified in the spleen and the vulva. The
      patient was discharged home on the fifth postoperative day and returned to normal
      activity within 2 weeks after operation. Two months after the surgery, computed
      tomography demonstrated a 3-cm pseudocyst in the region of the tail of the
      pancreas. As the patient was asymptomatic, this required no further therapy.
      Minimally invasive surgery together with hand assistance combines the advantages
      of both laparotomy and laparoscopy in the surgical management of selected lesions
      in the pancreas.

PMID- 9649040
TI  - Preliminary results of thoracoscopic Belsey Mark IV antireflux procedure.
AB  - Laparoscopic Nissen fundoplication has replaced open approaches for refractory
      gastroesophageal reflux disease (GERD) in many major medical centers. Here we
      report our preliminary results of the Belsey Mark IV antireflux procedure
      performed by video-assisted thoracoscopy (VATS-Belsey). Fifteen patients
      underwent VATS-Belsey. The indications for surgery included GERD refractory to
      medical therapy (n=10), achalasia (n=2), diffuse esophageal spasms (n=1),
      epiphrenic esophageal diverticulum (n=1), and paraesophageal hernia (n=1). The
      median operative time was 235 min. There were three conversions to open
      minithoracotomy (8-10 cm) necessitated by severe adhesions (n=2) and repair of a
      gastric perforation (n=1). The median hospital stay was 4 days. Postoperative
      complications included persistent air leaks, requiring discharge with a Heimlich
      valve in one patient. There were no perioperative deaths. At a median follow-up
      of 19 months, ten patients (66%) were asymptomatic and were not taking any
      antacids. One patient who had taken proton pump inhibitors preoperatively
      required postoperative H2 blockers for mild heartburn. In three patients,
      recurrent GERD symptoms (mean follow-up 6 months) led to laparoscopic takedown of
      the Belsey and Nissen fundoplication. One patient with achalasia, who had
      recurrent dysphagia after 1 year of relief following VATS myotomy and Belsey,
      underwent esophagectomy. The Belsey Mark IV antireflux procedure is technically
      feasible by VATS with minimal morbidity. However, our preliminary results suggest
      that open thoracotomy for Belsey Mark IV should remain the standard operation for
      GERD with poor esophageal motility when a thoracic approach is desired. We have
      modified our approach to laparoscopic partial fundoplications (Toupet or Dor) for
      severe GERD and poor esophageal motility when an abdominal approach is possible.

PMID- 9649041
TI  - Complications in laparoscopic colorectal resection: main types and prevention.
AB  - Most colorectal procedures can be done laparoscopically, as has been described by
      many authors. In the first 5 years of colorectal laparoscopic surgery, many
      complications have ensued, such as intestinal perforation, bleeding, infection,
      anastomotic leakage, and dehiscence. In 146 patients who underwent laparoscopic
      procedures from December 1991 to August 1996, 92 colorectal resections were
      performed. Most resections were performed for malignant diseases (48.9%) and the
      most common surgical procedure was rectosigmoidectomy (32.6%). Sixty-six patients
      (71.7%) were female, and the mean age was 59.4 years. Transoperative
      complications occurred in three patients (3.3%): one sigmoid perforation, one
      rectal perforation, and one case of left ureter transection. Postoperative
      complications occurred in 24 patients (29.3%): anastomotic leakage (4),
      intestinal perforation (1), incisional hernia (4), wound infection (8), shoulder
      pain (1), dehiscence of perineal wound (4), and colostomy necrosis (2). We
      concluded that laparoscopic colorectal resection is a safe surgical method and
      that the rate of complications is similar to that of the conventional method.

PMID- 9649042
TI  - Endoscopic transanal rectal stricturoplasty.
AB  - This is a report of the techniques used and the outcome in two patients who
      underwent endoscopic transanal rectal stricturoplasty. Both patients had rectal
      strictures at the site of previous colorectal stapled anastomosis, and had failed
      to respond to balloon dilatation. The stricturoplasties were carried out with the
      use of a laparoscopic linear cutter passed transanally. In one patient a
      colonoscope was used to visualize the stricture, whereas in the second patient a
      laparoscope (passed transanally) was used. The operating times were 65 and 59
      min, respectively. There were no complications, and both patients were discharged
      the next day. Both patients are asymptomatic after 9 and 7 months of follow-up. A
      colonoscopy carried out at 6 months has shown patent anastomosis in both
      patients. Endoscopic transanal rectal stricturoplasty is a safe and effective
      technique in dealing with benign rectal strictures and can be performed in an
      outpatient basis.

PMID- 9649043
TI  - Retroperitoneal endoscopic lumbar sympathectomy with balloon dissection:
      experience with a cadaveric model.
AB  - The objective of this study was to determine the feasibility of retroperitoneal
      endoscopic lumbar sympathectomy with balloon dissection technique using a
      cadaveric model. Retroperitoneal endoscopic lumbar sympathectomy was performed on
      10 cadavers. The procedure was combined with balloon dissection to provide easier
      visualization and more working space. The outcome was successful in eight
      cadavers. Average operating time was 40 min, and visualization was good. The only
      major technical problems were perforation of the peritoneum and air leak into the
      abdomen. It was concluded that retroperitoneal endoscopic lumbar sympathectomy
      with balloon dissection has the advantages of minimal invasiveness, clear
      visualization, and controlled blunt dissection. The use of a cadaveric model may
      improve the clinical learning curve.

PMID- 9649044
TI  - Laparoscopic cholecystectomy for the various types of gallbladder inflammation: a
      prospective trial.
AB  - Laparoscopic cholecystectomy (LC), the procedure of choice for elective
      cholelithiasis, is now also used in the management of acute cholecystitis. In the
      various types of gallbladder disease, favorable and unfavorable conditions may
      influence the conversion and complication rates. Information about these
      conditions may help elucidate the optimal circumstances for LC or indicate when
      the procedure is best avoided. We attempted to perform emergency LC on 215
      patients with acute cholecystitis. The procedure was successful in 171 patients
      (79.5%), and conversion to open cholecystectomy (OC) was needed in 44 (20.5%).
      Complications occurred in 37 patients (17%). Uncomplicated acute cholecystitis
      was associated with age <50 years, duration of complaint <48 h, temperature <38.5
      degrees C, a nonpalpable gallbladder, and an alkaline phosphatase >100 U/L. Acute
      gangrenous cholecystitis was associated with a negative gallbladder history,
      other associated diseases, temperature >38.5 degrees C, a palpable gallbladder,
      and serum bilirubin levels <1 mg/dl. Hydrops was associated with a temperature
      <38 degrees C and a leukocyte count of >12,000/cc3, and empyema of the
      gallbladder was associated with duration of complaint >48 h and a palpable
      gallbladder. The conversion rate of acute gangrenous cholecystitis (40%) was
      significantly higher than that of uncomplicated acute cholecystitis (8%) (p <
      0.00001, odds ratio=7.7), as well as that of empyema of the gallbladder (12.5%)
      (p=0.005, odds ratio=4.7). The conversion from LC to OC in uncomplicated acute
      cholecystitis was associated with male sex and with duration of complaint >24 h,
      and in gangrenous cholecystitis with age >60 years, a nonpalpable gallbladder,
      and a leukocyte count of >15,000/cc3. The complication rates of acute
      cholecystitis, hydrops, empyema of the gallbladder, and gangrenous cholecystitis
      were 16%, 7%, 22%, and 21%, respectively (p = NS). The total complication rate in
      acute cholecystitis tended to be associated with a duration of complaint >48 h
      and in gangrenous cholecystitis with male sex, age >60 years, other associated
      disease, larger bile stones, and elevated serum bilirubin levels. Generally, LC
      is safe in all forms of cholecystitis, with acceptably low conversion and
      complication rates, excluding gangrenous cholecystitis. In gangrenous
      cholecystitis, a conversion rate of approximately 40% is expected. Predictors of
      conversion and complications may be particularly helpful in planning the
      laparoscopic approach to acute gangrenous cholecystitis. Patients >60 years of
      age, with a nonpalpable gallbladder and with a leukocyte count >15,000/cc3,
      frequently need conversion. In men >60 years old, with other associated disease,
      with larger bile stones, and with elevated serum bilirubin levels, complications
      are frequently expected. Under these conditions, laparoscopic approach should be
      undertaken by especially experienced teams, or OC should be considered.

PMID- 9649045
TI  - Laparoscopic vs. open cholecystectomy in patients aged 65 and older.
AB  - Laparoscopic cholecystectomy (LC) has displaced open cholecystectomy (OC) in the
      management of cholelithiasis. However, there are few studies on the role of this
      technique in patients who run a high risk of surgical complications. We performed
      a prospective study in 264 patients aged >65 years undergoing surgery for
      symptomatic cholelithiasis. They were divided into two groups according to the
      surgical technique performed: OC (131 patients) and LC (133 patients). Conversion
      from LC to OC was necessary in 11 patients (8.3%). Mean surgery time was 70.9 min
      for the OC group and 75 min for the LC group. The LC group had a lower rate of
      postoperative complications (13.53%) than the OC group (23.6%). The incidence of
      mild complications was similar in both groups; however, the rate of moderate
      complications was significantly higher in the OC group. Hospital stay was
      significantly longer in the OC group (9.9 days) than in the LC group (3.71 days).
      These results suggest that LC should be indicated in elderly patients, as they
      are better than those obtained with with OC and involve a lower morbidity rate
      and shorter hospital stay.

PMID- 9649046
TI  - Laparoscopy-assisted endoscopic bowel anastomosis stenosis revision with stapler:
      report of two cases.
AB  - Anastomosis stenosis is a complication after bowel surgery. We performed
      laparoscopy-assisted endoscopic revision of bowel anastomosis stenosis with a
      stapler in two cases: first, for secondary anastomosis stenosis 14 months after
      sigmoid colon resection, and second, for inadequate-size primary anastomosis
      after segmental colon resection requiring immediate revision. A stapler, an
      endoscopic linear cutter Endopath ETS (Ethicon Endo-Surgery, Cincinnati, Ohio,
      U.S.A.), is transanally inserted and fired once into the stricture to enlarge the
      inner lumen. The procedure seems to be fast and safe, less invasive, and cost
      effective. This new technique can be used to avoid open surgery in cases of
      postoperative anastomosis stenosis as well as initially to increase the
      anastomosis diameter of the lower colon.

PMID- 9649047
TI  - Omental flap obtained by laparoscopic surgery for reconstruction of the chest
      wall.
AB  - The reconstruction of complex defects of the chest wall after infection of the
      sternotomy wound presents a great challenge. Various options have been described
      for these reconstructions using muscle and omental flaps to fill the space and
      cover the defect. A case of reconstruction of a large defect of the chest cage
      and abdominal wall in a 62-year-old patient is presented. After surgery for
      revascularization of the myocardium, the patient developed mediastinitis,
      osteomyelitis, and necrosis of the sternum. The pectoralis major muscle was
      utilized for the reconstruction, but total loss of the flap occurred. After
      debridement, an omental flap obtained by laparoscopy was employed based on the
      left gastroepiploic artery. The omentum was transposed without complications
      through the abdominal wall defect. An overlay skin graft with the omentum as
      receptor bed completed the closure. There are advantages in using minimally
      invasive videolaparoscopy compared with laparotomy in obtaining the omentum, with
      the same result regarding reconstruction of the defect.

PMID- 9649048
TI  - Postoperative ulcer and hemorrhage: an uncommon complication of laparoscopic
      Nissen fundoplication.
AB  - An unusual postoperative complication of ulceration and hemorrhage during the
      postoperative period of a Nissen fundoplication in a patient with severe chronic
      periesophagitis is presented. In a review of the literature we could not find a
      similar report. The possible etiopathogenic mechanisms are discussed, and
      preventive measures are suggested.

PMID- 9649049
TI  - Outcome of laparoscopic transabdominal preperitoneal inguinal hernia repair.
AB  - The long-term efficacy of laparoscopic inguinal hernia repair is unknown. This
      retrospective study was conducted to determine the efficacy of this operation in
      comparison with the open technique and to evaluate the possible factors of
      recurrence. We have evaluated the clinical outcome in a group of patients who
      underwent laparoscopic procedures between January 1995 and December 1996, with
      the aim of assessing the incidence of recurrence and of long-term complications.
      Sixty-three patients underwent laparoscopic transabdominal preperitoneal repair
      by use of a large mesh. We were able to examine 58 of these patients at a median
      follow-up time of 15 months since their operation. Four patients had developed a
      recurrence, and two patients had significant symptoms consistent with nerve
      damage. The recurrence rate of 7% is similar to that reported for open operations
      but higher than that reported for early follow-up after laparoscopic operations.
      Our study illustrates the value of long-term follow-up for the assessment of
      efficacy following laparoscopic inguinal hernia surgery.

PMID- 9649050
TI  - Endoscopic surgery of the neck: a new frontier.
AB  - Endoscopic dissection and surgical intervention of the neck is a safe and
      technically feasible option. A cavity for the operation is made by sharp
      dissection after preliminary CO2 insufflation of the fascial planes to induce
      surgical emphysema. We successfully performed three endoscopic
      parathyroidectomies and five endoscopic hemithyroidectomies without any
      complication. The technical details and factors affecting the result of the
      operation are described here.

PMID- 9649051
TI  - Anterior sacroiliac fusion: a new video-assisted endoscopic technique.
AB  - We present a case of sacroiliac fusion performed for an intraarticular
      osteochondroma of the sacroiliac joint, which was the cause of severe pain and
      disability. Excision of the lesion and sacroiliac fusion were successfully
      performed by utilizing minimally invasive surgical techniques. Although the
      application of this technique requires a dedicated and highly experienced team,
      the encouraging result of our first case, with minimal morbidity and disability
      due to the operation, induces us to recommend this technique in sacroiliac
      fusion, especially when fusion is combined with additional procedures such as
      drainage, biopsy, or excision.

PMID- 9649052
TI  - Needlescopic retrograde cholecystectomy.
AB  - Needlescopic surgery is a refinement of laparoscopic surgery wherein instruments
      smaller than 3 mm are used. The advantage is the minute wounds that heal
      imperceptibly. Initial reports of needlescopic cholecystectomy were confined to
      uninflamed gallbladders where the antegrade technique was invariably used. This
      case demonstrates a needlescopic cholecystectomy by the retrograde approach for
      an inflamed gallbladder.

PMID- 9649053
TI  - Unretrieved gallstone presenting as an inguinal mass.
AB  - We describe a case of a patient 6 months after laparoscopic cholecystectomy who
      presented with inguinal pain and a mass. At inguinal exploration, the patient was
      found to have an unretrieved gallstone.

PMID- 9649054
TI  - Laparoscopic external drainage of a pancreatic pseudocyst associated with
      periportal collaterals.
AB  - A pseudocyst of the pancreas was detected in a 44-year-old man with alcoholic
      chronic pancreatitis. Ultrasound-guided puncture and drainage were attempted but
      were unsuccessful because of unexpected bleeding from the collateral veins around
      the cyst wall. Consequently, a laparoscopic puncture was performed and proved to
      be effective.

PMID- 9649055
TI  - A further case of junction of the cystic duct into the left hepatic duct: a real
      risk for iatrogenic lesions of the bile ducts.

PMID- 9649056
TI  - Uraemic myopathy: fact or fiction.

PMID- 9649057
TI  - Plasma exchange in myasthenia gravis.

PMID- 9649058
TI  - Metabolic acidosis and nutritional status of patients receiving continuous
      ambulatory peritoneal dialysis (CAPD)

PMID- 9649059
TI  - Use of single dose low-molecular-weight heparin in long hemodialysis.
AB  - Low-molecular-weight (LMW) heparin has recently been used for anti-coagulation in
      maintenance hemodialysis. The LMW heparin was administered as a single bolus in
      hemodialysis that usually lasted for four hours or less. The regimen for
      administering LMW heparin in hemodialysis of longer duration (5 hours or more) is
      not well documented and manufacturers recommend a supplementary dose equivalent
      to one-quarter of the initial dose to be given at 4 hours after the commencement
      of hemodialysis. In this study, we explored whether administering a single dose
      of LMW heparin is feasible in hemodialysis of longer duration. Maintenance five
      hour hemodialysis sessions were performed in nine uremic patients with two
      different heparin regimens: single dose of LMW heparin (nadroparin) 12,500 ICU
      AXa at the beginning of dialysis or a priming dose of nadroparin 10,000 ICU AXa
      at the beginning of dialysis followed by a supplementary dose of nadroparin 2,500
      ICU AXa at the beginning of the fifth hour of dialysis. Clots in the airtraps or
      clotting of the dialyser were not observed in hemodialysis with the single dose
      heparin regimen. The anti-Xa activities at different time intervals during
      dialysis were above the therapeutic range of 0.5 U/ml except towards the end of
      the hemodialysis treatment. There was no difference between anti-Xa activities
      determined in dialysis sessions using two different regimens of LMW heparin at
      any individual time interval. The anti-thrombotic effect determined by the area
      under the time response curve for anti-Xa activity was comparable in the two LMW
      heparin regimens. Hence, our findings suggest a single bolus dose of LMW heparin
      (nadroparin) at 12,500 ICU AXa provides adequate, safe, and effective anti
      coagulation for five-hour hemodialysis. This practice is convenient and avoids
      the necessity of administering a double dose of LMW heparin.

PMID- 9649060
TI  - Exhaustion of vascular endowment in hemodialysis: proposal for a permanent inlet
      access.
AB  - The subcutaneous reservoir is a new vascular access for patients on regular
      hemodialysis (HD). A double chamber in Titanium- Pirolytic Carbon with siliconic
      boreable superior caps is inserted in to a subcutaneous subclavian side, and
      always in subcutis connected to two siliconic catheters located in the right
      jugular resulting in the right atrium. The puncture of each chamber is performed
      with a special hemodialysis-cannula telescopically assembled on a "dilatation
      tube", in which a stylet is inserted. In correct sequence, the cutaneous planes
      and the caps are bored, dilated, and finally the HD cannula after sliding over
      the previous structures is positioned in the inner chamber, closing the HD
      circuit. In our study two patients were implanted, with a survival of 24 months,
      good compliance, no cardiovascular impairments and lack of catheteral pathology.

PMID- 9649061
TI  - Myoglobin clearance during continuous veno-venous hemofiltration with or without
      dialysis.
AB  - The management of acute myoglobinuric renal failure, the major complication of
      rhabdomyolysis, continues to be a treatment dilemma for the clinician as limited
      therapeutic options are available. Previously, we have demonstrated that
      continuous arteriovenous hemofiltration (CAVH) is an effective technique for
      removing myoglobin in an animal model. In the present study, swine were
      administered four grams of equine myoglobin intravenously and underwent the
      continuous veno-venous hemofiltration (CVVH) procedure for six hours each.
      Animals were studied in each of the following groups: CVVH at a pump rate 100
      ml/minute, CVVH at a pump rate 200 ml/minute and CVVH at a pump rate 100
      ml/minute plus dialysis at a dialysate flow rate of one Liter/h. Once the
      filtering process was initiated there was a rapid and sustained production of
      ultrafiltrate in all groups. The amount of myoglobin excreted in the
      ultrafiltrate over the six-hour filtering period was 688, 948 and 570 mg which
      corresponded to 17, 24 and 14 percent of the administered dose, respectively, for
      the three treatments. In comparison to previous CAVH experiments, CVVH removed
      more circulating myoglobin and the addition of the dialysis component did not
      appear to improve removal. Based on these findings, it appears that the CVVH
      hemofiltration system is a viable option for the removal of systemic myoglobin.

PMID- 9649062
TI  - Reduction of mononuclear cytokine production in hemodialysis patients treated
      with steam-sterilized low-flux polysulphone membranes.
AB  - An increased cytokine production, correlated with long term complications of
      uremic disease, has been described during hemodialysis. To identify possible
      differences in the cytokine release of differently sterilized membranes, we
      enrolled six uremic patients on chronic hemodialysis. The patients underwent
      dialysis with ETO-sterilized low-flux polysulphone membranes (F6, Fresenius AG)
      for at least three months (A1), they were then switched to steam-sterilized
      polysulphone membranes (F6-HPS Fresenius AG) and further evaluations after one
      (B1) and two months (B2) were carried out. A final evaluation (A2) was made one
      month after switching back to F6 dialyzers. At each time period, samples were
      drawn to measure IL-1beta released by cultured mononuclear cells (MN). Moreover,
      dialysate samples were collected to test endotoxin levels. C3a and C5a levels
      were assessed at 0, 5, 15 and 60 min from starting hemodialysis. Anti-ETO IgE
      levels were also assayed at A1, B1 and A2. The LAL test revealed a good quality
      dialysate. The mean pre-dialysis IL-1beta levels were 215 pg/million cells at A1;
      falling to 49 at B1, and 54 at B2 (p<0.01); there was then a sharp rebound at A2:
      284, p<0.01. Post-dialysis levels followed the same pattern. No correlation
      between the dialysate endotoxin level and cytokine release was found. Complement
      activation did not change and in all the phases of the study no anti-ETO IgE was
      detected in any of the subjects. Our data suggest that the steam sterilized
      polysulphone membrane induces a lower cytokine release than the ETO sterilized
      membrane, although the mechanism by which it does so remains to be clarified.

PMID- 9649063
TI  - A new method of mechanical circulatory support with an implantable multichamber
      pump system (IMPS): presentation and first experimental results.
AB  - This paper presents a new cardiac support device for left ventricular failure
      which consists of two inflatable bellows positioned dorsally and ventrally to the
      left ventricle. The implantable multichamber pump system (IMPS) is driven by a
      pneumatic pump system and controlled by a microcomputer using ECG-trigger and
      pacemaker modules. It was implanted via thoracotomy in 8 pigs. The circulatory
      parameters were measured in the animals on beta-blockers, with cardiac failure
      and in ventricular fibrillation with an activated (IMPS on) and deactivated (IMPS
      off) system. IMPS significantly increased the left ventricular pressure (LVPsys
      IMPS off: 63 +/- 6 mmHg vs IMPS on: 96 +/- 8 mmHg) and the blood pressure in the
      common carotid artery (BPca, IMPS off: 69/38 mmHg vs IMPS on: 95/40 mmHg). The
      IMPS proved to be highly efficient in the therapy of animals with acute cardiac
      failure and in ventricular fibrillation in the experimental model. Apart from its
      efficiency the advantages with this system are the ease of handling and its high
      biocompatibility due to the lack of contact with circulating blood.

PMID- 9649064
TI  - Development of vibrating flow pump for left ventricular assist circulation.
AB  - Vibrating flow pump (VFP) can generate high frequency oscillated blood flow
      within 10-40 Hz. In this study, new type VFP was developed as a ventricular
      assist device. Left Ventricular assist circulation using VFP were performed as
      aseptic animal experiments using goats. hemodynamic parameters were recorded
      continuously at awake state. Driving frequency of VFP was 25 Hz and pump flow
      rate was controlled to approximately 2 l/min. Frequency of VFP was 25 hz and pump
      flow rate was controlled to approximately 2 L/min. Frequency analysis method was
      used for analyzing hemodynamics. The peak of power was observed at 25 Hz from the
      Fourier transformation of blood flow waveform. Systemic vascular resistance was
      decreased by the start of left ventricular assistance using oscillated blood
      flow. No fatal arrhythmia was observed during this study. As the conclusion, new
      type VFP has a sufficient performance for left ventricular assistance. Small size
      blood pump may be enabled by the oscillated blood flow because VFP is driven at
      high frequency moving with short stroke volume.

PMID- 9649065
TI  - High density culture of immortalized liver endothelial cells in the radial-flow
      bioreactor in the development of an artificial liver.
AB  - Liver endothelial cells are important components of the tissue along the hepatic
      sinusoid. They are responsible for microcirculation in the liver and scavenger
      functions. It would therefore be important to include these cells in any hybrid
      type of artificial liver in addition to hepatocytes. However, it is difficult to
      culture these cells in vitro. The development of a liver endothelial cell line,
      which maintains the characteristics of the primary culture, would thus be of
      great benefit in the development of an artificial liver. In the present study we
      established immortalized liver endothelial cells from the liver of an H-2Kb-tsA58
      transgenic mouse, which harbors the SV40 TAg gene. Hepatic sinusoidal cells
      isolated from H-2Kb-tsA58 mouse proliferated in the presence of gamma-interferon
      at 33 degrees C. Four clones were established, out of which clone M1 had the
      highest amounts of PGI2 production, as well as plasminogen activator activity and
      internalized acetylated low density lipoprotein. On culture dishes the M1 cells
      grew individually and spread. Sieve plates on the cell surface were not readily
      visible, but small pores were detected under electron microscopic observation.
      These results suggest that M1 clone cells originated from liver endothelial
      cells. Moreover it was possible to culture the immortalized liver endothelial
      cells in a radial-flow bioreactor for 5 days, with a maximum 6-keto prostaglandin
      F1alpha production of 25 microg per day. This suggests that immortalized liver
      endothelial cells and a radial-flow bioreactor can prove useful tools in the
      development an artificial liver.

PMID- 9649066
TI  - Salvage and reinfusion of chyle in closed chest injury.
AB  - The aim of this study was to describe a system of salvaging and reinfusing chyle
      which accumulated in the right pleural cavity of a patient after a thoracic duct
      lesion caused by a closed chest injury associated with amyelic fracture of the
      dorsal spine D10-D11. The chyle was collected in a reservoir (BT 844 Dideco),
      transferred by an electronic pump (BT 797 recovery Dideco) to a storage bag,
      microfiltered and then reinfused to the patient A solution was needed to prevent
      the patient with severe chylothorax, from having immunological and metabolic
      imbalance. The long period of conservative treatment with our system was imposed
      by the onset of acute post-traumatic myocardic infarction which delayed surgery.
      From experience gained, we can say that using total parenteral nutrition, chyle
      can not only be salvaged but also reinfused, respecting the strict rules of
      hygiene.

PMID- 9649067
TI  - Mechanical and dynamic aspects of voice production as related to voice therapy
      and phonosurgery.
AB  - Laryngeal framework surgery can change the position and tension of the vocal
      folds safely without direct surgical intervention in the vocal fold proper. Some
      23 years of experience with phonosurgery have proved its usefulness in treating
      dysphonia related to unilateral vocal fold paralysis, vocal fold atrophy, and
      pitch-related dysphonias . Meanwhile, much information about the mechanism of
      voice production has been obtained through intraoperative findings of voice and
      fiberscopic examination of the larynx . Based on such knowledge together with
      information obtained through model experiments, the human vocal organ was
      reconsidered mainly from the mechanical view point, and the roles of voice
      therapy and singing pedagogy were discussed in relation to phonosurgery. The
      vocal organ may not be an ideal musical organ and is rather vulnerable, but its
      potential is enormous.

PMID- 9649068
TI  - Suitability of minidisc (MD) recordings for voice perturbation analysis.
AB  - A new digital recording format, Minidisc (MD), shows promise for high-quality
      voice recordings. It is available in a portable size and uses magneto-optical
      recording techniques on a miniature compact disc. The disc can be recorded an
      unlimited number of times with essentially the same playback life span: however,
      the digital recording technique uses a data compression algorithm that may
      interfere with acoustic voice perturbation analysis. This study investigated what
      effects this compression may have and whether the MD format is viable for use in
      this application. The MD format was evaluated by traditional synthetic test
      signals used on recording devices. In addition, human phonation recorded on
      Digital Audio Tape (DAT) was used as the input to the MD. The output of the MD
      was then compared to the original DAT recording. The two signals were analyzed
      for long- and short-term perturbation measures, and their waveforms were visually
      inspected. The results indicated that the MD format performed as well as the DAT
      format in all areas of standard tests, with the exception of signal-to-noise
      (S/N) ratio. S/N ratio for the MD was approximately 10 dB less than for the DAT
      under normal operating conditions; however, in comparing perturbation measures on
      normal human vowels, there were no significant differences between the two
      formats, i.e., no distortions in voice perturbation were introduced by the MD
      record/playback process.

PMID- 9649069
TI  - A hardware-software system for analysis of video images.
AB  - The purpose of this paper is to describe a software/hardware system for the
      analysis of digitized video images and a number of applications for which it may
      be used. The system described includes a Macintosh computer, a frame-grabber
      board, and Image, a public domain software program available at no cost from the
      U.S. National Institutes of Health. In our clinic and laboratory, this system is
      routinely used to make quantitative measurements from videofluoroscopic x-ray
      images of dynamic swallow studies and studies performed to assess velopharyngeal
      dysfunction in speech. It can also be used to examine various laryngeal
      parameters obtained from videotaped endoscopic and stroboscopic examinations.
      With a videocamera attached to a microscope, the system permits quantitative
      analysis of tissue characteristics, e.g., thickness of epithelial or connective
      tissue layers of the vocal folds. The relatively low cost and ease of use of the
      image analysis system make it a particularly attractive option when quantitative
      assessment of clinical or research materials in video format is desirable.

PMID- 9649070
TI  - Optimal glottal configuration for ease of phonation.
AB  - Recent experimental studies have shown the existence of optimal values of the
      glottal width and convergence angle, at which the phonation threshold pressure is
      minimum. These results indicate the existence of an optimal glottal configuration
      for ease of phonation, not predicted by the previous theory. In this paper, the
      origin of the optimal configuration is investigated using a low dimensional
      mathematical model of the vocal fold. Two phenomena of glottal aerodynamics are
      examined: pressure losses due to air viscosity, and air flow separation from a
      divergent glottis. The optimal glottal configuration seems to be a consequence of
      the combined effect of both factors. The results agree with the experimental
      data, showing that the phonation threshold pressure is minimum when the vocal
      folds are slightly separated in a near rectangular glottis.

PMID- 9649071
TI  - Effects of lung volume on vertical larynx position during phonation.
AB  - The vertical position of the larynx seems to be relevant to voice function. As a
      high vertical larynx position is often seen in hyperfunctional and strained
      voices, a lowering of a habitually elevated larynx is sometimes a specific goal
      in clinical voice therapy and different larynx-lowering exercises are used to
      achieve this goal. Earlier investigations have shown that pitch and to some
      extent also vocal loudness are relevant to vertical larynx position. In the
      present investigation, we examine if lung volume affects vertical larynx
      position. Using a multi-channel electroglottograph, the larynx position was
      measured in 29 healthy, vocally untrained subjects, who phonated at different
      lung volumes, pitches, and degrees of vocal loudness. The main results were that
      high lung volume was clearly associated with a lower larynx position as compared
      to low lung volume. In addition, vertical larynx position was strongly correlated
      with pitch. Both of these dependencies were shown to be stronger in males than in
      females. Our results suggest that lung volume is a factor that is highly relevant
      to larynx height in untrained subjects.

PMID- 9649072
TI  - Data on subglottal pressure and SPL at varied vocal loudness and pitch in 8- to
      11-year-old children.
AB  - Phonation threshold pressure has been defined as the minimum subglottal pressure
      to generate phonation. Previous research has indicated that children may
      habitually employ higher subglottal pressures than adults. In the present
      investigation sound pressure level (SPL) and subglottal pressures at different
      pitch levels were measured at and above phonation threshold in nine children.
      Phonation threshold values were scattered in reasonable agreement with Titzes'
      prediction, although a discrepancy was noted regarding the frequency dependence
      in some voices. At normal conversational loudness and loudest level of phonation
      the children's Ps values were between two to four and four to eight times the
      predicted threshold values, respectively. At normal conversational loudness and
      habitual pitch subglottal pressures were lower than those previously observed for
      children, but similar to those found for female adults. The SPL in softest and
      loudest phonation were somewhat lower as compared to previous phonetogram data
      for children and for female adults. At normal loudness and habitual pitch the SPL
      values were similar to those of female adults. For a doubling of Ps mean SPL
      increased by 10.5 dB on the average.

PMID- 9649073
TI  - The effects of time constraints on phonatory stability in normally speaking adult
      women.
AB  - Forty normally speaking women sustained /a/ five times in two conditions, untimed
      and timed. In the untimed condition, phonation began whenever the subject felt
      ready. The timed task required subjects to begin phonation as quickly as possible
      after the examiner's signal. Conditions were counterbalanced across subjects.
      Jitter and shimmer values were obtained on a Kay Elemetrics Computerized Speech
      Lab (Pine Brook, NJ). Three distinct patterns of change emerged for jitter and
      shimmer from the untimed to the timed condition, reflecting either decreases,
      increases, or no change in values. These changes in jitter and shimmer values
      across conditions are related to a reaction time model of "bias toward accuracy."

PMID- 9649074
TI  - Relating objective measurements to expert evaluation of voice quality in Western
      classical singing: critical perceptual parameters.
AB  - Communication between voice pedagogues and voice scientists is often impeded by
      reliance on colorful and sometimes seemingly contradictory descriptions of vocal
      production and voice quality. A recent study identified perceptual criteria which
      are generally used by voice experts for the assessment of voice quality in
      classical singing. In the present study, performances by singers of various voice
      types and levels of accomplishment were rated by panels of expert voice teachers
      according to four perceptual criteria: "resonance/ring," "color/warmth,"
      "clarity/focus," and "appropriate vibrato." Subjective ratings were related to
      objective measurements taken from acoustic analysis of the voice signal. Possible
      acoustic correlates of critical perceptual parameters influencing judgments of
      voice quality were thus identified. Results could help bridge the terminology gap
      between vocal artists and scientists, and help to promote understanding of the
      way in which acoustic stimuli influence perception of voice quality.

PMID- 9649075
TI  - Voice problems and risk factors among aerobics instructors.
AB  - Fifty female and four male aerobics instructors completed a questionnaire
      pertaining to vocal problems and variables that could indicate an increased risk
      for developing problems. The questions concerned teaching experience, physical
      data regarding instructional facilities, method of voice projection, music
      volume, history of illness, allergies, voice loss, hoarseness, smoking habits,
      and knowledge of vocal hygiene. The results showed that a significant number of
      instructors experienced partial or complete voice loss (44%) during and after
      instructing, as well as increased episodes of voice loss, hoarseness, and sore
      throat unrelated to illness since they began instructing. Significant variables
      associated with voice problems included sore throat and hoarseness following
      instruction, and shouting to cue the participants. It was also found that very
      few instructors in this study had any knowledge of vocal hygiene techniques.

PMID- 9649076
TI  - Have women's voices lowered across time? A cross sectional study of Australian
      women's voices.
AB  - Various aspects of our communication are well known to have changed over time (1
      3). This article describes a cross-sectional study that examined the acoustic
      characteristics of two groups of Australian women aged 18-25 years from
      recordings made in 1945 and 1993 and investigated the possible changes in the
      voice across generations. Archival recordings from 1945 which had been used in a
      longitudinal study (4) were compared to recordings made in 1993. The results of
      this study show that women in 1993 have significantly deeper voices than women of
      the same age recorded in 1945. The possible factors influencing this change are
      discussed.

PMID- 9649077
TI  - Variations in adductor spasmodic dysphonia: acoustic evidence.
AB  - Acoustic analysis was used to gain information about the normal, as well as the
      abnormal acoustic events associated with adductor spasmodic dysphonia (ADSD).
      This analysis was completed to determine whether specific acoustic events could
      be used to differentiate the voice of individuals with ADSD from those with
      normal voice. A group comparison between 14 women diagnosed with ADSD and 14
      women (age-matched) with no evidence of vocal pathology or vocal dysfunction was
      completed. Phonatory breaks, aperiodicity, and frequency shifts, acoustic
      parameters previously identified in ADSD, were found throughout sustained vowel
      productions. The duration of the phonatory breaks and aperiodic segments was
      calculated and the amount of frequency shift was determined. The location of each
      acoustic event was marked relative to the onset of the vowel production. The
      subjects with ADSD presented with normal phonation and various amounts of each of
      the three acoustic parameters. Aperiodic segments primarily characterized the
      phonation of ADSD, followed by frequency shifts and phonatory breaks. The
      location of each of these acoustic events was within the midportion of the vowel
      production. The advantages of segmenting the acoustic waveform into these
      measures and separating the spasmodic events from normal phonation when examining
      laryngeal motor control of spasmodic dysphonics is discussed.

PMID- 9649078
TI  - Spasmodic dysphonia and vocal fold paralysis: outcomes of voice problems on work
      related functioning.
AB  - Patients at a university voice disorder clinic diagnosed with spasmodic dysphonia
      (SD, n = 68) or vocal fold paralysis (VFP, n = 57) reported vocal symptoms and
      adverse work outcomes in contrast to a nondisordered group (ND, n = 68). Patients
      with SD most frequently cited symptoms of effortfulness (57%) and weakness (54%),
      VFP cited hoarseness (70%) and weakness (60%), while the nondisordered reported
      hoarseness (28%). SD and VFP produced greater (p< .05) adverse work outcomes than
      the nondisordered in the past (SD: 65%, VFP: 41%, ND: 3%), potential future (SD:
      78%, VFP: 65%, ND: 19%), and current job performance (SD: 64%, VFP: 46%, ND: 2%).
      These disorders significantly disrupt socioeconomic outcomes and research is
      needed to improve functional ability and quality of life.

PMID- 9649079
TI  - Transoral laryngeal surgery under flexible laryngovideostroboscopy.
AB  - Although direct microlaryngoscopic surgery is universally accepted as the
      standard procedure for endolaryngeal surgery, general anesthesia and direct
      laryngoscopy are necessary during the procedure. Suspended laryngeal position
      also impedes intraoperative functional monitoring. Transoral laryngeal surgery
      under indirect laryngeal mirror or telescope has the advantage of sparing general
      anesthesia and direct laryngoscopy, but lower precision, difficult manipulation,
      and a high patient cooperation requirement make the procedure of limited
      application. Trying to overcome the above shortcomings, transoral laryngeal
      surgery under flexible laryngovideostroboscopy (FLVS) is undertaken at our
      institute. The surgery is performed at an outpatient office under topical
      anesthesia, with the help of high-resolution fiberoptic stroboscopy, high-quality
      CCD videocamera, and monitor. From October, 1993 to March, 1996, 157 patients
      with selected laryngeal problems were operated upon using this technique, and 150
      patients smoothly completed the procedure with satisfactory results. The
      technique is highly effective, especially for limited-manipulation, lower
      precision procedures and for patients who are not candidates for general
      anesthesia. With proper patient selection, this is a cost-effective surgery of
      low invasiveness and high applicability.

PMID- 9649080
TI  - Acoustical analysis and perceptual evaluation of tracheoesophageal prosthetic
      voice.
AB  - Voice analysis was performed on 21 "standard" laryngectomized, male patients with
      a Provox voice prosthesis, along with an age- and sex-matched control group of 20
      normal speakers, using acoustical analyses (MDVP and CSL, Kay Elemetrics Corp.),
      maximum phonation time measurements, and perceptual evaluations. Comparison
      between MDVP and CSL revealed that the latter was not useful for the analysis of
      laryngectomized prosthetic voices. In contrast, MDVP seems suitable for this
      purpose, and contains a large number of parameters that significantly
      differentiate between patient and control speakers, as did the perceptual ratings
      and the maximum phonation time. Fundamental frequency appeared to be comparable
      for patients and control speakers. A significant influence of stoma occlusion and
      age was found for some voice parameters. Factor analyses showed correlations
      between the different MDVP parameters and correlations between the MDVP
      parameters and the perceptual ratings.

PMID- 9649081
TI  - Microphone and electroglottographic data from dysphonic patients: type 1, 2 and 3
      signals.
AB  - Recently, it has been suggested that statistics which are dependent upon the
      reliable extraction of a single fundamental period, such as jitter and shimmer,
      are valid only for nearly periodic signals. This study explored the incidence of
      nearly periodic and nonperiodic microphone and electroglottographic signals
      obtained from 202 dysphonic patients. It was found that approximately 42% were
      type 1 (nearly periodic); approximately 35% were type 2 (containing bifurcations,
      modulations or subharmonic structure); and approximately 22% were type 3
      (chaotic). Discriminating between type 2 and 3 signals was very difficult for 40%
      of the signals which were ultimately rated type 3. This was due to the brevity of
      the apparently chaotic segment, and/or the persistence of some harmonic structure
      within the chaos. Irrespective of that difficulty, the results suggest that there
      may be a substantial incidence of nontype 1 signals in a given clinical
      population. It was concluded, therefore, that signal typing is a necessary step
      in the analyses of microphone and electoglottographic data.

PMID- 9649082
TI  - Assessing the role of case mix in cesarean delivery rates.
AB  - OBJECTIVE: Implicit in comparisons of unadjusted cesarean rates for hospitals and
      providers is the assumption that differences result from management practices
      rather than differences in case mix. This study proposes a method for comparison
      of cesarean rates that takes the effect of case mix into account. METHODS: All
      women delivered of infants at our institution from December 1, 1994, through July
      31, 1995, were classified according to whether they received care from community
      based practitioners (N=3913) or from the hospital-based practice that serves a
      higher-risk population (N=1556). Women were categorized according to both
      obstetric history (nulliparas, multiparas without a previous cesarean, multiparas
      with a previous cesarean) and the presence of obstetric conditions influencing
      the risk of cesarean delivery (multiple birth, breech presentation or transverse
      lie, preterm, no trial of labor for a medical indication). We determined the
      percent of women in each parity-obstetric condition subgroup and calculated a
      standardized cesarean rate for the hospital-based practice using the case mix of
      the community-based practitioners as the standard. RESULTS: The crude cesarean
      rate was higher for the hospital-based practice (24.4%) than for the community
      based practitioners (21.5%), a rate difference of 2.9% (95% confidence
      interval=0.4%, 5.4%; P=.02). However, the proportion of women falling into
      categories conferring a high risk of cesarean delivery (multiple pregnancy,
      breech presentation or transverse lie, preterm, no trial of labor permitted) was
      twice as high for the hospital-based practice (24.4% hospital, 12.1% community).
      The standardization indicates that if the hospital-based practitioners had the
      same case mix as community-based practitioners, their overall cesarean rate would
      be 20.1%, similar to the 21.5% rate of community providers (rate difference=
      1.4%, 95% confidence interval =-3.1%, 0.3%; P=.11). CONCLUSION: Standardization
      for case mix provides a mechanism for distinguishing differences in cesarean
      rates resulting from case mix from those relating to differences in practice. The
      methodology is not complex and could be applied to facilitate fairer comparisons
      of rates among providers and across institutions.

PMID- 9649083
TI  - Effect of maternal carbohydrate metabolism on fetal growth.
AB  - OBJECTIVE: To determine the effect of maternal carbohydrate metabolism and
      anthropometric characteristics on fetal growth. METHODS: Eight pregnant women in
      the third trimester with unexplained fetal growth restriction (FGR) and 11 women
      with normal pregnancies in the third trimester were evaluated for maternal
      carbohydrate metabolism, using oral glucose tolerance tests and hyperinsulinemic
      euglycemic clamps. These data and maternal anthropometric characteristics
      subsequently were related to relative birth weight, defined as observed birth
      weight x 100/50th percentile birth weight. RESULTS: The women with FGR
      pregnancies were more insulin sensitive than were controls (21.6+/-4.4 versus
      16.7+/-4.8 micromol/kg x min, P < .05) and showed reduced insulin and glucose
      areas under the curve (96,293+/-25,870 versus 145,291+/-49,356 pmol/L, P < .03;
      1057.0+/-184.7 versus 1210.1 +/-85.9 mmol/L, P < .05, respectively). No
      differences were seen in fasting plasma glucose, insulin and human placental
      lactogen samples, age, height, pregravid weight, weight gain, and parity. In all
      patients, maternal insulin sensitivity and weight gain correlated well with
      relative birth weight (r =-.65, P < .002; r=.68, P < .001, respectively). When
      the same analysis was computed separately in the groups, insulin sensitivity
      exhibited a strong negative correlation with relative birth weight in the FGR
      group but not in controls (r=-.84, P < .007; r=-.54, P=.08, respectively).
      Conversely, in control women the best correlation between relative birth weight
      and the other variables studied was seen with maternal weight gain (r=.82, P <
      .002). CONCLUSION: Women with unexplained FGR have a different glucose metabolic
      pattern than do normals. We speculate that increased insulin sensitivity leads to
      a reduction in metabolic substrates for fetal growth.

PMID- 9649084
TI  - Polycystic ovaries in women with gestational diabetes.
AB  - OBJECTIVE: To examine the occurrence of polycystic ovaries (PCO) in women with
      gestational diabetes mellitus (GDM). METHODS: This was a retrospective
      comparative study of ultrasonographic findings of ovaries in 31 women with GDM
      and 30 healthy controls matched according to maternal age and body mass index
      (BMI). Women who presented evidence of impaired glucose tolerance during
      pregnancy were excluded from the control group. Transvaginal ultrasonographic
      examination was performed during the follicular phase of the menstrual cycle,
      after breast-feeding had been discontinued. RESULTS: Polycystic ovary was a more
      frequent finding among women with GDM than among controls: 14 women with GDM
      (44%) and two controls exhibited PCO. No differences were found in BMI before
      pregnancy or in the weight gain during pregnancy between the groups. No
      difference was observed in the mean birth weight of the infants between the study
      groups. CONCLUSION: Polycystic ovaries were a common finding among women with
      GDM. The data suggest that women with PCO are at risk for developing GDM and
      should be screened accordingly.

PMID- 9649085
TI  - Elevated maternal serum relaxin concentrations throughout pregnancy in singleton
      gestations after superovulation.
AB  - OBJECTIVE: To test the hypothesis that superovulation results in elevated
      maternal circulating relaxin concentrations throughout the second and third
      trimesters of pregnancy, independent of the pattern of hCG secretion. METHODS:
      Two groups of women with singleton gestations were studied: a group of nine women
      who achieved pregnancy after stimulation with human menopausal gonadotropin and a
      group of six women who achieved pregnancy without prior stimulation. Peripheral
      blood samples were drawn approximately every 5 weeks throughout the second and
      third trimesters. Serum relaxin concentrations were measured using a human
      relaxin-specific enzyme-linked immunosorbent assay; hCG was measured by an
      immunofluorometric assay. RESULTS: The stimulated group had significantly higher
      relaxin levels throughout pregnancy (P=.007, multivariate analysis of variance)
      than did nonstimulated controls. The mean relaxin level in stimulated patients
      was 1.78 ng/mL (95% confidence interval [CI] 1.5, 2.17) and in nonstimulated
      subjects the level was 0.73 ng/mL (95% CI 0.59, 1.25). Spline fits demonstrated
      that stimulated patients had higher relaxin levels throughout the second and
      third trimesters. There was no significant difference in hCG concentrations
      between the two groups (P=.61). CONCLUSION: In singleton gestations after
      superovulation, maternal serum relaxin concentrations are significantly higher
      throughout the second and third trimesters of pregnancy. These differences are
      independent of the pattern of hCG secretion. It appears that luteal relaxin
      secretion is controlled by factors in addition to hCG.

PMID- 9649086
TI  - Neonatal group B streptococcal infection in a managed care population. Perinatal
      Group B Streptococcal Infection Study Group.
AB  - OBJECTIVE: In a health maintenance organization population, we determined the
      incidence of early-onset (at less than or equal to 7 days) neonatal group B
      streptococcal (GBS) disease, the sensitivity and prevalence of labor risk
      factors, the adherence to a protocol for intrapartum antibiotics, and the costs
      for care of and outcomes of affected infants. METHODS: Mothers and infants at
      four health maintenance organization hospitals in northern California in 1989 to
      1995 were studied retrospectively using computerized databases and chart review.
      In 1994, two of the four hospitals had adopted protocols similar to the ACOG
      recommendations for intrapartum antibiotics for women with labor risk factors
      (preterm, temperature 100.4F or higher, or rupture of membranes (ROM) 18 hours or
      more). RESULTS: Among the 79,940 live births, the incidence of early-onset
      neonatal GBS infection was higher among preterm than among term infants (3.1
      compared with 0.9 per 1000). Before protocol adoption, 68% of 65 infants with GBS
      had mothers with labor risk factors. Approximately 18% of all mothers had labor
      risk factors: 7.7% had preterm delivery, and 10.6% had term delivery with fever
      and/or ROM 18 hours or more. At the two hospitals that adopted GBS protocols, GBS
      incidence was reduced from 1.3 per 1000 in the preprotocol period to 0.8 per 1000
      in the postprotocol period (P=.08). Six cases of neonatal GBS occurred after
      protocol adoption. Of these, four were not preventable under the protocol and two
      might have been preventable if protocol had been followed. Three of the 19
      preterm infants with group B streptococcal disease died. CONCLUSION: Risk factor
      based protocols hold some promise to reduce GBS disease, but clinical strategies
      to promote protocol adherence are needed.

PMID- 9649087
TI  - Oral quinolone in the treatment of experimental polymicrobial puerperal infection
      in rabbits.
AB  - OBJECTIVE: To evaluate the efficacy of oral levofloxacin in the treatment of
      experimental polymicrobial puerperal infection in the rabbit. METHODS: Timed
      pregnant rabbits were anesthetized on day 29 or 30 of a 31-day gestation and 106
      colony-forming units each of Escherichia coli, group B streptococcus, and
      Staphylococcus saccharolyticus were inoculated endoscopically in the cervices.
      Labor was induced with intramuscular oxytocin 16 hours later if it had not
      occurred spontaneously. The animals then were observed every 3 hours for fever;
      when a temperature of 104F was reached, treatment was begun. Animals were
      assigned randomly in a blinded, placebo-controlled manner to received oral
      levofloxacin (10 mg/kg/day) or placebo and were treated twice daily for 4-5 days.
      The animals were killed and necropsy was performed 4-6 hours after the last dose.
      Specimens for culture were taken from uterine horns, peritoneum, and blood.
      Levofloxacin concentrations were determined from blood samples at necropsy.
      Clinical cure of fever, eradication of microbes, and presence of uterine
      abscesses at necropsy were assessed. RESULTS: Compared with placebo-treated
      rabbits, levofloxacin-treated animals had a significantly greater number of
      clinical cures (nine of 11 versus four of 12, P=.027) and significantly more
      eradication of E coli (ten of 11 versus five of 12, P=.022). Four uterine
      abscesses were seen in 12 placebo-tested animals, compared with none of 11
      levofloxacin-tested animals (P=.093). There was no difference in eradication of
      group B streptococcus between the two groups. No blood cultures were positive for
      organisms in any animal. Levofloxacin was detected in all treated animals, but at
      low levels (less than 1 microg/mL). CONCLUSION: Treatment of experimental
      puerperal infection with oral levofloxacin in rabbits resulted in significantly
      more clinical cures and eradication of E coli compared with treatment with
      placebo.

PMID- 9649088
TI  - Longitudinal assessment of endocervical canal length between 15 and 24 weeks'
      gestation in women at risk for pregnancy loss or preterm birth.
AB  - OBJECTIVE: To determine the weekly cervical shortening rates of the endocervical
      canal between 15 and 24 weeks' gestation in women at risk for pregnancy loss or
      spontaneous preterm birth. METHODS: We performed a retrospective cohort study of
      transvaginal sonographic measurements of the endocervical canal length done at
      least twice between 15 and 24 weeks' gestation in women at risk for pregnancy
      loss and spontaneous preterm birth. The ultrasound diagnosis of cervical
      incompetence was defined as progressive shortening of the endocervical canal
      length to 2 cm or less either spontaneously or after application of transfundal
      pressure. Multivariable linear regression models were developed to determine the
      weekly crude rate of endocervical canal length shortening rates in cases of
      competent cervices and incompetent cervices, with incompetent cervices further
      stratified as those diagnosed at 15-19 weeks' and 20-24 weeks' gestation.
      Comparisons of the models for weekly rate of endocervical canal length shortening
      were performed. RESULTS: The endocervical canal lengths were measured in 61 women
      (180 measurements) who did not develop ultrasound evidence of cervical
      incompetence and 28 women (103 measurements) who had ultrasound evidence of
      cervical incompetence. Between 15 and 24 weeks' gestation, competent cervices had
      a nonsignificant rate of endocervical canal length shortening (-0.03 cm/week).
      During this period in gestation, incompetent cervices had significantly greater
      endocervical canal length shortening (-0.41 cm/week, P < .001). The rate of
      endocervical canal length shortening of incompetent cervices diagnosed between 15
      and 19 weeks' gestation was -0.52 cm/week (P < .001). The rate of endocervical
      canal length shortening in incompetent cervices diagnosed between 20 and 24
      weeks' gestation was significant and varied from -0.49 cm/week to -0.80 cm/week
      at 20 and 24 weeks' gestation, respectively (P < .001). The models describing the
      rate of cervical shortening in the two groups of incompetent cervices were
      significantly different (P < .001). The sonographic detection of endocervical
      canal length shortening in the 28 cases of cervical incompetence was identified
      at a median (range) gestational age of 20 (16-24) weeks. CONCLUSION: Weekly rates
      of endocervical canal length shortening were established, which may be useful for
      detecting and managing cervical incompetence in high-risk women examined with
      cervical sonography.

PMID- 9649089
TI  - Preterm contractions in community settings: I. Treatment of preterm contractions.
AB  - OBJECTIVE: To explore how physicians in community hospitals (non-level III
      nursery facilities) diagnose preterm labor and treat women with preterm
      contractions. METHODS: Chart audits were performed for women presenting with
      preterm contractions at a network of 11 Wisconsin non-level III hospitals.
      RESULTS: Ninety percent (239 of 266) of the women presenting with premature
      contractions agreed to participate. The average gestational age was 31.6 weeks'
      gestation. Only 44 (17%) of these women had any cervical change with their
      contractions. However, tocolytic agents were used frequently, regardless of
      whether cervical changed occurred (61%) or not (76%, P=.10), and tocolytics were
      prescribed frequently upon discharge for those patients who left the hospital
      (54% of those with cervical change versus 62% in those without changes, P=.57).
      Examining the use of appropriate treatments for women who did deliver
      prematurely, we found that only 26% of women who delivered prematurely received
      antenatal antibiotics to prevent group B streptococcal disease in the newborn,
      and only 33% of those who delivered at 34 weeks' gestation or earlier received
      corticosteroids to accelerate fetal lung maturity. CONCLUSION: Women presenting
      at community hospitals with preterm contractions but no evidence of labor are
      overtreated frequently with agents of equivocal benefit, whereas those who have
      active labors and deliver are not receiving agents such as steroids or
      antibiotics that have been shown to benefit outcomes.

PMID- 9649090
TI  - Preterm contractions in community settings: II. Predicting preterm birth in women
      with preterm contractions.
AB  - OBJECTIVE: To examine risk factors for preterm delivery in women who present to
      nontertiary care hospitals with preterm contractions. METHODS: Women who
      presented to a network of community hospitals in Wisconsin with preterm
      contractions were followed until delivery. The main outcomes were preterm
      delivery before completion of 36 weeks of gestation and delivery within 1 week of
      initial presentation. RESULTS: Of the 266 women presenting with contractions over
      the 2-year study period, 90% (n=239) consented to participate. Multiple factors
      were associated with premature delivery, but when examined with a multivariate
      model, only four (ruptured membranes, multiple gestation, cervical effacement at
      least 80%, and nonwhite race) were associated with prematurity, whereas five
      (ruptured membranes, multiple gestation, cervical effacement at least 80%,
      dilation exceeding 1 cm, and being a nonsmoker) predicted delivery within 1 week.
      A decision model that combined the presence of ruptured membranes and effacement
      at least 80% could predict delivery at 34 weeks or less within 7 days of
      presentation with a sensitivity of 71% and a specificity of 98%. CONCLUSION: Only
      two clinical cues (ruptured membranes and effacement of the cervix of 80% or
      more) can predict premature delivery within 7 days. If these results are
      confirmed prospectively, women with either of these signs could be targeted for
      administration of steroids, antibiotics, or transfer to tertiary care facilities.

PMID- 9649091
TI  - Elective induction versus spontaneous labor: a case-control analysis of safety
      and efficacy.
AB  - OBJECTIVE: To investigate the incidence, efficacy, and safety of elective
      induction in a community teaching hospital over 1 year. METHODS: This is a
      retrospective case-control study of rate, safety, and efficacy of all term
      inductions with vertex presentations judged to be elective by chart analysis.
      Cases were matched one for one for age, parity, and pay status with controls in
      spontaneous labor. The elective induction women were compared with those in
      spontaneous labor using chi2 Student t test, and Fisher exact test. Potential
      risk factors for cesarean delivery and neonatal intensive care unit (NICU)
      admission were then selected and subjected to bivariate analysis. Stepwise
      logistic regression was applied to control for confounding and to select which
      risk factors were important for those end points. RESULTS: There were 461 case
      control pairs. The elective induction rate was 12.3%. Cesarean delivery was
      increased by elective induction in bivariate analysis (odds ratio [OR]=1.81,
      confidence interval [CI]=1.07, 3.08; power=.60). The cesarean delivery rate was
      8.7% (control 5.0%). In a multiple regression model of potential risk factors for
      cesarean delivery, nulliparity (OR=6.14, CI=2.90, 13.04), cervical priming
      (OR=3.06, CI=1.46, 6.40), oxytocin usage (OR=2.82, CI=1.03, 7.75), gestational
      age at least 287 days (OR=2.51, CI=1.38, 4.58), and birth weight at least 3800 g
      (OR=2.29, CI=1.27, 4.13) were significant, but elective induction and epidural
      anesthesia were not. Elective induction did not significantly increase the rate
      of NICU admission (4.6% versus control 3.9%). In a multiple regression model of
      potential factors predicting NICU admission, only a 5-minute Apgar score of at
      most 8 was significant (OR = 12.34, CI=6.01, 25.3). CONCLUSION: Elective
      induction is commonly practiced, safe, and efficacious. Cesarean delivery is
      increased significantly by nulliparity and/or an unfavorable cervix, among other
      factors, but not by elective induction itself.

PMID- 9649092
TI  - Association of sociodemographic variables with risk for very preterm birth in
      twins.
AB  - OBJECTIVE: To assess the influence of maternal race, age, marital status, and
      education on risk for earlier and later preterm births in twin pregnancies.
      METHODS: We analyzed 8109 white and 1906 black liveborn twin pregnancies in the
      Missouri Linked Sibship files for the years 1978-1990, using contingency tables
      and multiple logistic regression. RESULTS: Black twin gestations had 1.61-fold
      (95% confidence interval [CI] 1.46, 1.76) greater risk than whites for preterm
      birth before 34 weeks' gestation. However, there was no race difference after 33
      weeks. Among whites, teen age, unmarried status, and education fewer than 12
      years were independently associated with risk for delivery before 34 weeks in
      multivariate analysis (odds ratios [OR] 1.28-1.51, each P < or=.001). These
      associations were diminished or absent for preterm births after 33 weeks'
      gestation. White unmarried teen mothers with fewer than 12 years of education had
      1.83-fold (95% CI 1.39, 2.40) greater risk for preterm birth before 34 weeks'
      gestation compared with white married women more than 19 years of age with at
      least 12 years of education. In blacks, this difference was 1.47-fold (95% CI
      1.13, 1.92). In both races, these differences were absent after 33 weeks'
      gestation. CONCLUSION: Traditional sociodemographic risk factors were present for
      twin preterm birth, but mainly before 34 weeks' gestation. This, together with
      previous data from Missouri Linked Sibship files, indicates that dominant
      pathogenic mechanisms of early preterm birth in twin gestations are likely to be
      different from those causing later preterm twin birth. Therefore, gestational age
      should be accounted for in future studies seeking to identify predictive factors
      or biomechanisms for twin preterm birth.

PMID- 9649093
TI  - Fetal growth restriction at term: myth or reality?
AB  - OBJECTIVE: To evaluate the morbidity and mortality associated with the small for
      gestational age (SGA) fetus born at term to an otherwise uncomplicated pregnancy.
      METHODS: Small for gestational age, singleton newborns (birth weight below the
      tenth percentile for gestational age) born at 37-42 weeks' gestation were
      identified by medical record discharge coding. We excluded gestations complicated
      by structural or chromosomal abnormalities, maternal diabetes mellitus,
      preeclampsia, chronic hypertension, asthma, or renal, endocrine, or autoimmune
      disease. Three low-risk, appropriate for gestational age (AGA) fetuses, matched
      for gestational age at delivery, were selected randomly for each SGA fetus and
      served as controls. Maternal and neonatal data were abstracted via medical record
      review. Statistical analysis included chi2 Fisher exact test, and analysis of
      variance. RESULTS: There were 67 newborns in the study group and 201 in the
      control group. There were no fetal or neonatal deaths in any of these cases. The
      maternal age at delivery, prepregnancy weight, race, smoking status, weight gain
      during pregnancy, and neonatal gender did not statistically differ between the
      two groups. Compared with AGA infants, a larger proportion of SGA newborns had
      low 1-minute Apgar scores and SGA newborns were more likely to be admitted to the
      neonatal intensive care unit, and have respiratory distress, hypoglycemia,
      thrombocytopenia, and hyperbilirubinemia. They were also significantly more
      likely to be delivered by cesarean. CONCLUSION: The SGA newborn from an
      uncomplicated pregnancy delivered at term has increased neonatal morbidity
      compared with its AGA counterpart. These results dispute the notion that term
      growth restriction is a benign condition.

PMID- 9649094
TI  - Elevated umbilical cord plasma erythropoietin levels in prolonged pregnancies.
AB  - OBJECTIVE: To determine if umbilical cord plasma erythropoietin levels are
      elevated in pregnancies that continue beyond their expected date for delivery.
      METHODS: Erythropoietin was measured using an enzyme-linked immunosorbent assay
      in 124 appropriately grown newborns delivered from 37-43 weeks' gestation. Each
      woman had an uncomplicated labor and delivery course without evidence of fetal
      stress or meconium. The comparison was made between pregnancies ending at 37-40
      weeks' gestation and those at 41-43 weeks' gestation. RESULTS: There was no
      difference between the two groups in cord blood gases or Apgar scores at 1 and 5
      minutes. Cord plasma erythropoietin levels were significantly higher in
      pregnancies delivered after 41 completed weeks' gestation (41 or more weeks:
      48.0+/-7.1 mIU/mL, n=45 versus 37-40 weeks: 26.1+/-4.2 mIU/mL, n=79, P < .001).
      When compared with pregnancies delivered between 37 and 40 weeks, erythropoietin
      levels were significantly elevated in pregnancies delivered at either 41, 42, or
      43 weeks' gestation. CONCLUSION: In pregnancies reaching 41 weeks and beyond,
      cord plasma erythropoietin levels are significantly increased, indicating altered
      fetal oxygenation in some of these pregnancies. These results support the current
      practice of close fetal surveillance of prolonged pregnancies.

PMID- 9649095
TI  - Amniocentesis-related fetal loss: a cohort study.
AB  - OBJECTIVE: To assess the risk of fetal loss attributable to second-trimester
      amniocentesis. METHODS: A cohort study was undertaken among singleton pregnant
      women undergoing genetic amniocentesis and controls matched prospectively on a
      one-to-one basis, matched strictly for maternal age, parity, and socioeconomic
      status. Both groups were recruited at 15-24 weeks' gestation and observed until
      delivery. The fetal loss rates of the groups were compared. RESULTS: A total of
      2256 pairs were recruited to the study. After excluding those pairs lost to
      follow-up, those with fetal malformation, and those later proven to have major
      chromosomal abnormalities, 2045 matched pairs were compared by pregnancy
      outcomes. There were no significant differences in fetal loss rates, premature
      deliveries, or placental abruptions between the study and control groups (P >
      .05). However, this study did not have enough statistical power to identify
      differences of less than 1%. CONCLUSION: Second-trimester amniocentesis is
      probably not associated with a greater fetal loss rate than that of matched
      controls.

PMID- 9649096
TI  - Fetal heart rate and nuchal translucency in detecting chromosomal abnormalities
      other than Down syndrome.
AB  - OBJECTIVE: To evaluate whether the combined use of fetal heart rate (FHR) and
      nuchal translucency measurements would be useful in the prediction of fetal
      chromosomal abnormalities at 10-13 weeks' gestation. METHODS: In a prospective
      study, 1053 (553 reported previously) consecutive singleton pregnancies between
      10 and 13 weeks' gestation underwent chorionic villus sampling at our
      institution. Fetal heart rate and fetal nuchal translucency thickness were
      measured immediately before the invasive procedure. RESULTS: Thirty-five abnormal
      karyotypes were diagnosed, including 17 trisomy 21, seven trisomy 18, one trisomy
      13, one trisomy 9, four unbalanced translocation, two Klinefelter syndrome, one
      Turner syndrome, one deletion of chromosome 18, and one true mosaicism. Using 95%
      of normal ranges as the cutoff for both measurements, the detection rate for all
      chromosomal anomalies was 77.1%, with a false-positive rate (1-specificity) of
      7.7%, a positive predictive value of 25.7%, and a negative predictive value of
      99.2%. Fetal heart rate improved the sensitivity of nuchal thickness in trisomies
      21 and 18 (from 62.5% to 75%) and was particularly useful to detect other
      chromosomal anomalies (from 27.2% to 81.8%). CONCLUSION: Our findings suggest
      that there is an added role of FHR in ultrasound screening of chromosomal
      abnormalities, specifically for those other than trisomy 21 and 18. The value of
      a single measurement of fetal heart rate for screening purposes needs to be
      confirmed by further investigation in a low-risk population.

PMID- 9649097
TI  - Amniotic fluid complement C3 as a marker of intra-amniotic infection.
AB  - OBJECTIVE: To determine the value of amniotic fluid (AF) complement C3 as a
      marker of intra-amniotic infection and to compare complement C3 with other rapid
      markers of intra-amniotic infection. METHODS: One hundred four women with
      singleton gestations, in preterm labor with intact membranes, at 23-35 weeks'
      gestation underwent transabdominal amniocentesis. Amniotic fluid was analyzed for
      white blood cell (WBC) count, lactate dehydrogenase (LDH), glucose, Gram stain,
      and complement C3. Cultures for aerobes, anaerobes, and mycoplasma species also
      were performed. The median values of complement C3, WBC, LDH, and glucose were
      compared between the culture-positive and -negative groups. Complement C3 was
      compared with WBC count, LDH, glucose, and Gram stain for sensitivity,
      specificity, positive and negative predictive values, and accuracy in the
      prediction of a positive AF culture. Descriptive statistics, receiver operating
      characteristic curve, Fisher exact test, and Wilcoxon rank-sum test were used for
      analysis. RESULTS: The prevalence of positive cultures was 11.5% (12 of 104). The
      culture-positive group had a significantly higher median C3 (7.0 mg/dL) than the
      median C3 (3.0 mg/dL) of the culture-negative group (P < .001). Also, the median
      values of WBC (1120.5 cells/mm3) and LDH (2697 U/L) were significantly higher and
      the median glucose (6.5 mg/dL) was significantly lower among women with positive
      AF cultures than among women with negative AF cultures (WBC=1 cell/mm3; LDH=165
      U/L; glucose=45 mg/dL; P < .001). Eleven of the 12 culture-positive cases had a
      C3 of 5 mg/dL or more, whereas four of the 92 culture-negative cases had a C3 of
      5 mg/dL (P < .001). Nine of the 12 culture-positive cases but none of the 92
      culture-negative cases had a C3 of 6 mg/dL or more (P < .001). The relative risks
      of a positive AF culture were 65.27 (95% confidence interval [CI] 9.08, 469.27)
      and 31.67 (95% CI 10.40, 96.43) times greater among women with AF complement C3
      levels of 5 and 6 mg/dL or more, respectively. Depending on the cutoff point
      used, complement C3 had similar or higher sensitivity, specificity, positive
      predictive value, and negative predictive value for intra-amniotic infection when
      compared with WBC count, LDH, glucose and Gram stain. CONCLUSION: Amniotic fluid
      complement C3 has value in the diagnosis of intra-amniotic infection in preterm
      labor with intact membranes. Complement C3 is available readily and compares
      favorably with other rapid markers of AF infection. This study supports the
      general concept of fetal inflammatory response to microbial invasion of AF.

PMID- 9649098
TI  - Isolation of Ureaplasma urealyticum from the amniotic cavity and adverse outcome
      in preterm labor.
AB  - OBJECTIVE: To determine the relationship between the presence of Ureaplasma
      urealyticum in the amniotic cavity and adverse maternal and perinatal outcome in
      women with preterm labor. METHODS: Amniocentesis was performed in 181 patients
      with preterm labor and intact membranes. Amniotic fluid (AF) was cultured for
      aerobic and anaerobic bacteria and mycoplasmas. Patients were divided into three
      groups according to the results of AF culture: those with negative AF cultures
      (n=160), those with positive AF cultures and in whom the only microbial isolate
      was U urealyticum (n=11), and those with positive cultures for non-ureaplasmas or
      mixed microorganisms (n=10). Survival techniques were used for analysis. RESULTS:
      The prevalence of positive AF cultures in which the only microbial isolate was
      Uurealyticum was 6.1% (11 of 181), and of positive cultures with non-ureaplasmas
      or mixed microorganisms was 5.5% (10 of 181). The amniocentesis-to-delivery
      interval was significantly shorter in patients with positive cultures limited to
      U urealyticum than in those with negative cultures (median 7 [range 0.1-149]
      hours versus median 264 [0.1-2659] hours, P < .001). Preterm delivery within 48
      hours, 72 hours, and 7 days was more frequent in patients with U urealyticum in
      the AF than in those with sterile AF (48 hour: 91% versus 33%; 72 hour: 91%
      versus 36%; 7 days: 100% versus 45%, P < .001 for each). Patients with positive
      AF cultures limited to U urealyticum had a significantly higher rate of adverse
      perinatal outcome than those with negative culture. Adverse outcomes included low
      gestational age at birth, low birth weight, histologic chorioamnionitis,
      significant neonatal morbidity, and perinatal death. CONCLUSION: Microbial
      invasion of the amniotic cavity with U urealyticum is a risk factor for impending
      preterm delivery and adverse perinatal outcome.

PMID- 9649099
TI  - Invasive cervical cancer in human immunodeficiency virus-infected and uninfected
      hospital patients.
AB  - OBJECTIVE: To compare the prevalence of invasive cervical cancer in women with,
      and in women without, human immunodeficiency virus (HIV) infection, so as to
      evaluate the inclusion of invasive cervical cancer in the AIDS surveillance case
      definition. METHODS: The Sentinel Hospital Surveillance System for HIV Infection
      collected data and serum specimens that remained after clinical testing of
      persons who received inpatient or outpatient care at 14 hospitals with high HIV
      prevalence. We analyzed data on invasive cervical cancer obtained from medical
      record review and HIV serostatus from white, black, and Hispanic women in the age
      groups 20-34, 35-44, and 45-54 years. RESULTS: In 1994 and 1995, 2684 (6.6%) of
      the 40,524 women sampled were HIV infected. Of the HIV-positive women, 28 had
      invasive cervical cancer (10.4 per 1000 women) and of the HIV-negative women, 236
      had invasive cervical cancer (6.2 per 1000 women, relative risk [RR] 1.7, 95%
      confidence interval [CI] 1.1, 2.5). The prevalence of invasive cervical cancer
      was higher for HIV-positive than for HIV-negative black women aged 20-34 (RR 3.8;
      CI 1.7, 8.5) and Hispanic women aged 20-34 (RR 7.3; CI 1.4, 37.1) and 35-44 (RR
      3.9; CI 1.1, 14.7) years. Twenty-six of the 28 cases of invasive cervical cancer
      in HIV-positive women were in women known to be HIV-positive during admission.
      CONCLUSION: The prevalence of invasive cervical cancer was higher for women who
      were HIV positive than for women who were HIV negative. This lends support to the
      inclusion of invasive cervical cancer in the revision of the surveillance case
      definition for AIDS in 1993.

PMID- 9649100
TI  - Oncogene expression: long-term compared with short-term survival in patients with
      advanced epithelial ovarian cancer.
AB  - OBJECTIVE: To determine if oncogene overexpression in patients with advanced
      epithelial ovarian cancer correlates with survival. METHODS: Twenty-two women
      with stage III ovarian cancer, observed for a median of 66 (range 48-204) months
      were compared with 30 with a median survival of 18 (range 2-28) months. Using
      immunocytochemistry, tumors were immunostained for overexpression of p53, c-erb-B
      2, and epidermal growth factor receptor and were evaluated quantitatively for
      expression of estrogen receptor, progesterone receptor, and Ki-67 antigen, a
      marker of cellular proliferation. RESULTS: The median age of long-term survivors
      was 52 (range 30-76) years compared with 55 (range 36-80) years for short-term
      survivors. Optimal cytoreduction was achieved in 11 of the 22 long-term survivors
      compared with seven of the 30 short-term survivors, a significant difference
      (P=.05). The average level of Ki-67 expression was 43% in long-term survivors and
      64% in short-term survivors (P=.007). Overexpression of p53 was seen in 54% of
      long-term survivors and 80% of short-term survivors (P=.05). A combination of Ki
      67 level of 50% or greater plus p53 overexpression was seen in 22% of long-term
      survivors compared with 68% of short-term survivors (P=.005). Epidermal growth
      factor receptor, c-erb-B-2, estrogen receptor, and progesterone receptor statuses
      did not differ significantly between the two groups. CONCLUSION: Markers that did
      not correlate with survival included the hormone receptors, estrogen receptor and
      progesterone receptor, and the oncogenes, c-erb-B-2 and epidermal growth factor
      receptor. Long-term survivors with advanced ovarian cancer were more likely to
      have had an optimal cytoreduction and lower levels of Ki-67 antigen expression
      and were less likely to overexpress p53 than were short-term survivors.

PMID- 9649101
TI  - A randomized controlled trial of early postoperative feeding in gynecologic
      oncology patients undergoing intra-abdominal surgery.
AB  - OBJECTIVE: To evaluate the safety and efficacy of early oral feeding after intra
      abdominal surgery in gynecologic oncology patients. METHODS: During a 1-year
      period, 200 gynecologic oncology patients undergoing intra-abdominal surgery were
      enrolled in a randomized controlled trial of early compared with traditional oral
      postoperative feeding. Patients allocated to early postoperative oral feeding
      began a clear liquid diet on the first postoperative day and then advanced to a
      regular diet as tolerated. Patients allocated to traditional postoperative oral
      feeding received nothing by mouth until return of bowel function (defined as the
      passage of flatus in the absence of vomiting or abdominal distention), then began
      a clear liquid diet, and advanced to a regular diet as tolerated. RESULTS: Age,
      case distribution, surgery length, blood loss, and first passage of flatus were
      similar in the early and traditional feeding groups. Significantly more patients
      in the early group developed nausea. Despite this, the incidence of vomiting,
      abdominal distention, incidence and duration of nasogastric tube use, and
      percentage of patients who tolerated clear liquid and regular diets on the first
      attempt were comparable in both groups. Time to development of bowel sounds, time
      to initiation of clear liquid and regular diets, and hospital stay were
      significantly longer in the traditional group. Major complications (eg,
      pneumonia, atelectasis, and wound complications) and febrile morbidity occurred
      equally in both groups. There were no known anastamotic complications or
      aspirations in either group. Postoperative changes in hematologic indices and
      electrolytes were comparable in both groups. CONCLUSION: Early postoperative
      feeding in gynecologic oncology patients undergoing intra-abdominal surgery is
      safe and well tolerated.

PMID- 9649102
TI  - Thermal balloon and rollerball ablation to treat menorrhagia: a multicenter
      comparison.
AB  - OBJECTIVE: To compare the clinical efficacy and safety of a thermal uterine
      balloon system with hysteroscopic rollerball ablation in the treatment of
      dysfunctional uterine bleeding. METHODS: Two hundred fifty-five premenopausal
      women were treated in a randomized multicenter study comparing thermal uterine
      balloon therapy with hysteroscopic rollerball ablation for the treatment of
      menorrhagia. Preprocedural and postprocedural menstrual diary scores and quality
      of-life questionnaires were obtained. Twelve-month follow-up data are presented
      on 239 women. RESULTS: Twelve-month results indicated that both techniques
      significantly reduced menstrual blood flow with no clinically significant
      difference between the two groups as reflected by return to normal bleeding or
      less (balloon 80.2% and rollerball ablation 84.3%). Multiple quality-of-life
      questionnaire results were also similar, including percent of patients highly
      satisfied with their results (balloon 85.6% compared with rollerball 86.7%). A
      90% decrease in diary scores was seen in more than 60% of patients in both
      groups. Procedural time was reduced significantly in the uterine balloon therapy
      group. Intraoperative complications occurred in 3.2% of the hysteroscopic
      rollerball patients, whereas no intraoperative complications occurred in the
      thermal balloon group. CONCLUSION: In the treatment of dysfunctional uterine
      bleeding, uterine balloon therapy is as efficacious as hysteroscopic rollerball
      ablation and may be safer.

PMID- 9649103
TI  - Tumor growth and dissemination after laparotomy and CO2 pneumoperitoneum: a rat
      ovarian cancer model.
AB  - OBJECTIVE: To compare tumor growth, intraperitoneal implantation, and abdominal
      wall metastasis after laparotomy and CO2 pneumoperitoneum in a rat ovarian cancer
      model. METHODS: To mimic intraoperative rupture of an ovarian tumor in a syngenic
      rat ovarian carcinoma model, 10(5) malignant cells were injected
      intraperitoneally after a 5-cm vertical midline laparotomy or after the
      insufflation of a CO2 pneumoperitoneum achieved with 4 mmHg or 10 mmHg intra
      abdominal pressure. Two weeks later, the intraperitoneal tumor growth and the
      tumor dissemination were evaluated semiquantitatively with a scoring system. The
      scores attributed to each organ were added to calculate the dissemination score
      of each animal. RESULTS: The mean (+/-SD) dissemination score was 83.4+/-12 in
      the laparotomy group and 67.3+/-16 and 71.9+/-17 in the 4 and 10 mmHg CO2
      pneumoperitoneum groups, respectively (P < .01). The scores for the peritoneum
      were 21.8+/-3.8 in the 10 mmHg pneumoperitoneum group and 18+/-2.4 in the
      laparotomy group (P < .01). In the laparotomy group, the implant found along the
      midline scar accounted for a mean of 62.6+/-15% of the peritoneal score, whereas
      the trocar site metastases did not influence the peritoneal score in the
      pneumoperitoneum groups. The incidence of wound metastasis was 96% in the
      laparotomy group and 55% and 54% in the 4 mmHg and 10 mmHg pneumoperitoneum
      groups, respectively. CONCLUSION: In this model, tumor growth was greater after
      laparotomy than after laparoscopy, but peritoneal tumor dissemination was more
      severe after CO2 pneumoperitoneum.

PMID- 9649104
TI  - Comparison of bimanual examination with ultrasound examination before
      hysterectomy for uterine leiomyoma.
AB  - OBJECTIVE: To correlate the preoperative bimanual examination with ultrasound
      examination with regard to estimating the size of enlarged nongravid
      leiomyomatous uteri. METHODS: We performed a retrospective review of 161 patients
      who underwent hysterectomy for uterine leiomyoma between January 1994 and
      December 1994 and between July 1995 and April 1996. Uterine size was estimated
      clinically by bimanual examination. Ultrasound reports were reviewed. Uterine
      weights and dimensions in pathology reports were compared with findings on
      bimanual examination and ultrasonography. Body mass index (BMI) was calculated
      and patients were divided into two groups, one with BMIs of more than 30 and
      another with BMIs of less than or equal to 30. RESULTS: Ultrasound examination
      was ordered in 111 patients (68.9%) preoperatively. There was a strong
      correlation between the bimanual examination findings and the ultrasound
      dimensions. The equation for this relationship is ultrasound length (cm)=3.68 +
      0.68 x number of weeks (r=.78, P < .001). Ultrasound length also was related
      strongly to size given in the pathologic reports; the equation for this
      relationship is ultrasound length (cm)=2.94 + 0.75 x pathology length (cm)
      (r=.73, P < .001). The correlation between bimanual examination and ultrasound
      findings was similar in obese and in nonobese patients, when uterine size could
      be estimated. CONCLUSION: There is a strong correlation between bimanual and
      ultrasound examinations with regard to determining the size of leiomyomatous
      uteri. Routine ultrasound is not indicated when an experienced examiner can
      assess uterine size. Ultrasonography may be appropriate when physical assessment
      is difficult, as in the case of obesity.

PMID- 9649105
TI  - Urinary tract injuries after hysterectomy.
AB  - OBJECTIVE: To evaluate the nationwide incidence and characteristics of urinary
      tract injuries after laparoscopic hysterectomy, total abdominal hysterectomy,
      supracervical abdominal hysterectomy, and vaginal hysterectomy. METHODS: We
      analyzed retrospectively 142 urinary tract injuries after hysterectomy, reported
      to the National Patient Insurance Association in Finland from 1990 through 1995.
      The Finnish Hospital Discharge Register collects data on procedures from all
      hospitals, and 62,379 hysterectomies were carried out during the study period.
      RESULTS: The total incidence of ureteral injury after all hysterectomies was 1.0
      of 1000 procedures: 13.9 of 1000 after laparoscopic, 0.4 of 1000 after total
      abdominal, 0.3 of 1000 after supracervical abdominal, and 0.2 of 1000 after
      vaginal hysterectomy. Difficulties during an operation with a ureteral injury
      were encountered in 51%, 76%, 100%, and 100%; the failure rates of primary repair
      of a ureteral injury were 5%, 12%, 0%, and 0%; and the convalescence times after
      a ureteral injury were 86 days, 94 days, 71 days, and 47 days after laparoscopic,
      abdominal, supracervical abdominal, and vaginal hysterectomies, respectively. The
      incidence of bladder injury was 1.3 of 1000 procedures. Sixty-five percent of
      reported bladder injuries were fistulas, giving an incidence of vesicovaginal
      fistula of 0.8 of 1000 procedures after all hysterectomies: 2.2 of 1000 after
      laparoscopic, 1.0 of 1000 after total abdominal, 0 of 1000 after supracervical
      abdominal, and 0.2 of 1000 after vaginal hysterectomy. Difficulties during an
      operation with a bladder injury were encountered in 53%, 37%, 100%, and 0%; the
      failure rates of primary repair of a simple bladder injury were 5%, 18%, 0%, and
      0%; the failure rates of primary repair of a vesicovaginal fistula were 17%, 20%,
      0%, and 0%; and the convalescence times after a bladder injury were 51 days, 118
      days, 71 days, and 99 days after laparoscopic, abdominal, supracervical
      abdominal, and vaginal hysterectomy, respectively. CONCLUSION: The risk of
      ureteral injury is higher after laparoscopic hysterectomy compared with
      traditional hysterectomies.

PMID- 9649106
TI  - Prognostic validity of neoplastic cells with notable nuclear atypia in
      endometrial cancer.
AB  - OBJECTIVE: To investigate how the architectural grade of endometrial
      adenocarcinoma should be adjusted in the presence of neoplastic cells with
      notable nuclear atypia in order to assign the histologic grade. METHODS: Four
      hundred seventy-six patients with stage I endometrial cancer (endometrioid type)
      who were surgically treated in a single institute formed the study population.
      The architectural grade and the proportion of tumor cells with notable nuclear
      atypia were examined for each case. The effects of notable nuclear atypia on the
      disease-free survival of each architectural grade were analyzed. RESULTS: The
      disease-free survival of architectural grade 1 and grade 2 tumors was
      significantly affected and was worse than that of architectural grade 3 tumors
      when more than 25% of the tumor cells showed notable nuclear atypia. Tumors that
      had 26% to 50% of neoplastic cells with notable nuclear atypia showed a similar
      probability of recurrence as did tumors that had more than 50% of neoplastic
      cells with notable nuclear atypia. CONCLUSION: The series suggests that the
      upgrading of architectural grade 1 or 2 tumors, in which more than 25% of the
      neoplastic cells show notable nuclear atypia, into a grade 3 tumor may be more
      practical than upgrading by one architectural grade 1 or 2 tumors, in which the
      majority of neoplastic cells show notable nuclear atypia.

PMID- 9649107
TI  - Cytology and colposcopy after loop electrosurgical excision: implications for
      follow-up.
AB  - OBJECTIVE: To analyze risk factors associated with residual and recurrent lesions
      after loop electrosurgical excision procedure and to assess the reliability of
      cytology and colposcopy in detection of these lesions. METHODS: Cytology and
      colposcopy were used to follow up 288 women after treatment by loop
      electrosurgical excision 3-6 months, 9-15 months, and 24-36 months after the
      procedure. RESULTS: The mean (+/-standard deviation) postoperative follow-up was
      39+/-13 months (range 24-68 months). Treatment failure, defined as the
      persistence or recurrence of a cervical lesion, was observed in 20 patients
      (6.9%). The endocervical localization of the initial lesion (adjusted relative
      risk [RR] 13.7; 95% confidence interval [CI] 1.3, 150.1; P < .05) and incomplete
      excision (adjusted RR 9.1; 95% CI 3.0, 27.3; P < .001) were the only independent
      risk factors for treatment failure. In six cases, a second treatment was
      performed before the first cytologic and colposcopic visit because of incomplete
      excisions. The remaining 14 treatment failures were diagnosed by postoperative
      cytology and colposcopy, ten after the first visit, three after the second, and
      one after the third. To diagnose the treatment failures, colposcopy and cytology
      provided complementary information at the first (P < .001) and second
      postoperative visits (P < .05). Although the sensitivity of cytology was not
      significantly improved by the association of both methods, the latter decreased
      the number of residual lesions overlooked by cytology alone and contributed to
      the diagnosis of 95% of treatment failures in less than 2 years. CONCLUSION: The
      high detection rate obtained by combining cytology and colposcopy during the
      first 2 postoperative years may allow more leisurely follow-up schedules after
      that time and may reduce the consequences of subsequent loss to follow-up.

PMID- 9649108
TI  - The use and failure rates of protective equipment to prevent blood and bodily
      fluid contamination in the obstetric health care worker.
AB  - OBJECTIVE: To determine the frequency of use and the failure rate of protective
      equipment by obstetric staff during common obstetric procedures. METHODS: A
      prospective observational study was conducted of multiple obstetric procedures.
      The presence, area of specialty, level of training, and gender of each team
      member were recorded along with the use of protective equipment (cap, mask,
      eyewear, gown, gloves, and shoe protection). These observations were recorded by
      two trained observers. Blood and bodily fluid contamination of the protective
      equipment was quantified and recorded for each person. A forensic medicine
      reagent (Luminol; Cluefinders Inc., Tampa, FL) was used to detect trace amounts
      of blood on the inner surface of a selected subset of gowns that had gross
      external contamination but no obvious penetration. RESULTS: Two hundred forty-one
      obstetric procedures were observed involving 1022 medical personnel. The use of
      at least one piece of protective equipment was noted 88% of the time. Compliance
      with universal precautions by attending and resident physicians in all deliveries
      (vaginal, forceps, vacuum, cesarean) was observed in 65 (25.2%) medical
      personnel. The use of protective equipment varied by the type of procedure, area
      of specialty, and level of training of the team member. In the gowns examined
      with the forensic medicine reagent, 44% of the cases demonstrated laboratory
      evidence of penetration. The frequency of gown failure varied with the type of
      surgical gown used. CONCLUSION: Despite the mandate in the medical community for
      universal precautions, the rate of compliance remains low. However, even among
      the compliant medical staff, protective equipment labeled as impenetrable has a
      high failure rate.

PMID- 9649109
TI  - Effect of maternal hydration on fetal renal pyelectasis.
AB  - OBJECTIVE: To assess the effect of maternal hydration on fetal pyelectasis.
      METHODS: Thirteen pregnant women with fetal pyelectasis and 13 controls matched
      for gestational age were recruited during the same period. Ultrasound and Doppler
      studies and maternal urine specific gravity measurements were carried out before
      and after maternal oral hydration. The data were analyzed by either a two- or
      three-factor analysis of variance. RESULTS: Renal artery Doppler pulsatility
      index was significantly greater in the study group than in the controls (2.37
      versus 1.83; P=.009) and this finding was unaffected by maternal hydration
      status. After hydration, the maternal urinary specific gravity decreased
      significantly (1.018 versus 1.009; P < .001), the amniotic fluid index (AFI)
      increased significantly (14.27 versus 18.24 cm; P < .001), and the fetal renal
      pelvis diameter increased significantly (0.29 versus 0.46 cm; P=.002) in both the
      study and control groups. Renal pelvis anteroposterior diameter after hydration
      did not differ significantly whether the fetal bladder was full or empty (0.7
      versus 0.6 cm; P=.1). In this study, each subject served as her own control (ie,
      from before to after hydration). Three of 13 controls met the diagnostic criteria
      for pyelectasis after maternal hydration. CONCLUSION: The AFI increases after
      maternal hydration in both normal fetuses and those with pyelectasis. The fetal
      renal pelvis anteroposterior diameter increases with maternal hydration in both
      normal fetuses and those with pyelectasis and is independent of the state of the
      fetal bladder. The renal artery Doppler pulsatility index is significantly
      greater in fetuses with pyelectasis than in controls.

PMID- 9649110
TI  - Operational improvement of gynecologic laparoscopic operating room services: an
      internal review.
AB  - BACKGROUND: To reorganize reusable laparoscopic instrumentation to promote
      instrument accessibility, minimize instrument breakage, eliminate infrequently
      used instruments on permanent trays, and help control maintenance costs.
      TECHNIQUE: The Robert Wood Johnson University Hospital Gynecologic Steering
      Committee evaluated during a 5-month period the storage, use, and maintenance of
      gynecologic laparoscopic instrument sets used in the surgical suite. Acting on
      this data, the committee oversaw the following changes. Infrequently used
      instruments were removed from permanent trays and separately packaged. Two types
      of gynecologic laparoscopy trays were prepared: one for laparoscopic bilateral
      tubal ligations and one for both diagnostic and operative laparoscopy. A double
      decker compartmentalized tray in which instruments were sterilized and stored
      replaced the extant single-layer ones in which instruments were stacked on each
      other. To facilitate instrument identification and function, a surgical manual
      was compiled with photographs of each instrument and a description of its use.
      EXPERIENCE: After implementation of these changes, maintenance and sterilization
      costs for a 10-month period were compared with those for the previous 10 months.
      There was a savings of $13,889. The ratio of total costs divided by number of
      cases performed during the two study periods was also compared. There was a
      savings of $31 per case. CONCLUSION: Savings were achieved by reorganizing this
      operating room's handling of reusable gynecologic laparoscopy equipment. By
      eliminating infrequently used instruments from the permanent trays and by using a
      double decker compartmentalized tray that was used during surgery, sterilization,
      and storage, both sterilization costs and maintenance costs were reduced.

PMID- 9649111
TI  - The Gupta-Frank clamp for salpingo-oophorectomy at vaginal hysterectomy.
AB  - BACKGROUND: When performing a vaginal hysterectomy, removal of the tubes and
      ovaries can be either necessary or desirable. We describe our experience with a
      new instrument called the Gupta-Frank clamp for performing vaginal salpingo
      oophorectomy at the time of vaginal hysterectomy. INSTRUMENT: The stainless steel
      Gupta-Frank clamp is 260 mm long, and its shanks are curved to avoid impedance
      from the vaginal walls. The 70-mm jaws have a smooth curve, which allows both the
      round and infundibulopelvic ligaments to be incorporated into a single clamp
      bite. Each jaw has three serrated grooves, which interlock with the corresponding
      jaw grooves to give a 6-mm-wide atraumatic nonslip area. EXPERIENCE: We have used
      this instrument in 18 women undergoing bilateral salpingo-oophorectomy at the
      time of vaginal hysterectomy. A single clamp bite on each side was sufficient to
      accomplish salpingo-oophorectomy in all cases. There were no major complications.
      CONCLUSION: Salpingo-oophorectomy performed vaginally at the time of vaginal
      hysterectomy with the Gupta-Frank clamp is feasible and is accomplished easily
      and safely.

PMID- 9649112
TI  - A comprehensive resident training program in operative endoscopy.
AB  - We describe a structured and uniform resident experience in operative endoscopy
      and analyze the costs of implementing such a program at an urban academic medical
      center. The residency curriculum at Northwestern Memorial Hospital incorporates a
      five-part approach to endoscopy training: weekly endoscopy rounds, an annual
      animal laboratory for residents, an individual animal laboratory, supervision by
      skilled endoscopic surgeons, and a laparoscopic training facility. Thirty-two
      residents have completed the training over 4 years. The annual cost of the entire
      program is $34,500, which can be offset partially by vendor support. A
      comprehensive and continuous endoscopic training program is an important and
      affordable part of resident education.

PMID- 9649113
TI  - Prediction of preterm delivery by fetal fibronectin: a meta-analysis.
AB  - OBJECTIVE: To assess the cervicovaginal fetal fibronectin test to predict preterm
      delivery. DATA SOURCES: We searched MEDLINE, Current Contents, Index Medicus, and
      proceedings of meetings for studies published between 1991 and June 1997. METHODS
      OF STUDY SELECTION: Inclusion criteria were prospective cohort study; test
      performed between 20 and 36 weeks' gestation; fetal fibronectin measured by a
      previously described assay, with a cutoff level set at 50 ng/mL; test results not
      disclosed to women or physicians; and fewer than 20% of study participants
      excluded from the analysis. TABULATION, INTEGRATION, AND RESULTS: Twenty-nine
      relevant studies were stratified according to the prevalence of preterm delivery,
      the number of tests performed, and delivery before 34, 35, or 37 weeks.
      Sensitivities, specificities, and likelihood ratios were calculated in each
      study. The summary estimates of the likelihood ratio for tests yielding positive
      results or tests yielding negative results along with their 95% confidence
      intervals (CIs) were computed in each stratum according to a random-effects
      model. All summary likelihood ratios for a test yielding positive results
      indicated a significant association with preterm delivery. The strongest
      association was found between a single test with positive results and delivery
      before 37 weeks in a low-risk population (likelihood ratio 7.5; 95% CI 4.6,
      12.3). This association also was found in high-risk women (likelihood ratio 3.5;
      95% CI 2.6, 4.6). In high-risk women, a test yielding negative results was
      associated with a reduction in risk of preterm delivery (likelihood ratio 0.4;
      95% CI 0.3, 0.5). CONCLUSION: Fetal fibronectin in cervicovaginal secretions is
      associated with preterm delivery in both high-risk and low-risk women.

PMID- 9649114
TI  - Correlates of postmenopausal female hormone use among black women in the United
      States.

PMID- 9649115
TI  - Toxicity to neuroblastoma cells and spheroids of benzylguanidine conjugated to
      radionuclides with short-range emissions.
AB  - Radiolabelled meta-iodobenzylguanidine (MIBG) is selectively taken up by tumours
      of neuroendocrine origin, where its cellular localization is believed to be
      cytoplasmic. The radiopharmaceutical [131I]MIBG is now widely used in the
      treatment of neuroblastoma, but other radioconjugates of benzylguanidine have
      been little studied. We have investigated the cytotoxic efficacy of beta, alpha
      and Auger electron-emitting radioconjugates in treating neuroblastoma cells grown
      in monolayer or spheroid culture. Using a no-carrier-added synthesis route, we
      produced 123I-, 125I-, 131I- and 211At-labelled benzylguanidines and compared
      their in vitro toxicity to the neuroblastoma cell line SK-N-BE(2c) grown in
      monolayer and spheroid culture. The Auger electron-emitting conjugates
      ([123I]MIBG and [125I]MIBG) and the alpha-emitting conjugate ([211At]MABG) were
      highly toxic to monolayers and small spheroids, whereas the beta-emitting
      conjugate [131I]MIBG was relatively ineffective. The Auger emitters were more
      effective than expected if the cellular localization of MIBG is cytoplasmic. As
      dosimetrically predicted however, [211At]MABG was found to be extremely potent in
      terms of both concentration of radioactivity and number of atoms ml(-1)
      administered. In contrast, the Auger electron emitters were ineffective in the
      treatment of larger spheroids, while the beta emitter showed greater efficacy.
      These findings suggest that short-range emitters would be well suited to the
      treatment of circulating tumour cells or small clumps, whereas beta emitters
      would be superior in the treatment of subclinical metastases or macroscopic
      tumours. These experimental results provide support for a clinical strategy of
      combinations ('cocktails') of radioconjugates in targeted radiotherapy.

PMID- 9649116
TI  - Thrombin promotes platelet-mediated melanoma cell adhesion to endothelial cells
      under flow conditions: role of platelet glycoproteins P-selectin and GPIIb-IIIA.
AB  - We investigated the role of platelets in human melanoma cell (line 397)
      interaction with vascular endothelial cells (ECs) under flow conditions. The
      ability of the tumour cells to adhere to the EC monolayer was significantly
      reduced by application of flow at a shear rate of 250 s(-1). A 2.2-fold increase
      in tumour cell adhesion to ECs under flow was observed upon addition of thrombin
      receptor agonist peptide (TRAP)-activated platelets but not resting platelets. A
      similar increase (2.5-fold) in tumour cell adhesion to ECs under flow was
      observed when the tumour cells were incubated with resting platelets on thrombin
      treated ECs. However, thrombin treatment of the ECs alone had no effect on tumour
      cell adhesion in the absence of platelets. The enhancement of tumour cell
      adhesion to ECs by TRAP-activated platelets was virtually abolished by blockade
      of the platelet glycoproteins P-selectin and GPIIb-IIIa by monoclonal antibodies.
      Blockade of P-selectin also inhibited the direct adhesion of TRAP-activated
      platelets to ECs, but did not affect the interaction of the tumour cells with
      platelets immobilized on subendothelial extracellular matrix (ECM). Blockade of
      GPIIb-IIIa inhibited both platelet-EC and platelet-tumor cell interactions. Our
      results indicate that tumour cell adhesion to the endothelium under flow is
      enhanced by platelets under conditions that allow platelet adhesion to ECs.
      Inhibition studies suggest that activated platelet adhesion to ECs is mediated by
      P-selectin and GPIIb-IIIA, and tumour cell adhesion to EC-bound platelets--mainly
      by GPIIb-IIIa.

PMID- 9649117
TI  - Amplification and expression of the ABC transporters ARA and MRP in a series of
      multidrug-resistant leukaemia cell sublines.
AB  - E1000, the most drug-resistant subline from the E-series (CCRF-CEM/E16 to E1000),
      has been previously shown to express high mRNA levels from two ABC transporter
      genes associated with multidrug resistance, ARA and MRP. The expression and
      amplification of both genes has now been characterized for each member of the E
      series of drug-resistant sublines and is reported here. Both ARA [detected by
      reverse transcriptase polymerase chain reaction (RT-PCR)] and MRP (detected by
      Northern blot analysis) were expressed at low levels in the sensitive parental
      CEM cell line. An equivalent level of MRP mRNA expression was detected throughout
      the CEM, E16, E25 and E50 sublines, and there was increasing expression in the
      E100, E200 and E1000 sublines. ARA expression was not detected in the E16, E25,
      E50 and E100 sublines but was detected by both RT-PCR and Northern blot analysis
      in the E200 and E1000 sublines. Southern blot analysis indicated the increased
      levels of MRP and ARA expression resulted from gene amplification and that MRP
      was first amplified in the E100 subline and ARA in the E200 subline, suggesting
      that the two genes were not initially co-amplified. Cytogenetic analysis of E1000
      cells demonstrated a large addition to chromosome 16p, around the region where
      the ARA and MRP genes are located. Increased expression of ARA is associated with
      increased colchicine resistance in the E-series of sublines and combined with MRP
      may account for their resistance phenotype.

PMID- 9649118
TI  - Regulation of interferon responses in medulloblastoma cells by interferon
      regulatory factor-1 and -2.
AB  - Transcriptional activator interferon regulatory factor (IRF)-1 and repressor IRF
      2 are known to play a critical role in the regulation of interferon (IFN)
      responses and oncogenesis in fibroblasts. Although these two factors are
      expressed in many tissues, including the brain, the role of IRFs in the central
      nervous system (CNS) has not been elucidated. We analysed a medulloblastoma cell
      line, ONS-76, as a CNS-derived model system and generated its derivatives, R1 and
      R2 cells, which constitutively expressed each mouse IRF-1 and IRF-2 cDNA at high
      levels. By viral infection, R1 and R2 cells showed IFN-beta gene expression 3 h
      earlier than the control ONS-76 (C-76) cells, with 2.46- and 2.24-fold increase
      in IFN-beta production respectively. In the presence of cycloheximide, virally
      induced IFN-beta gene expression of C-76 cells was suppressed, whereas R1 and R2
      cells produced IFN-beta 7.5- and 2.2-fold higher than C-76 cells respectively. On
      the other hand, induction of IFN-inducible genes was enhanced in R1 cells but was
      suppressed in R2 cells compared with C-76 cells. These results demonstrate that
      IRF-1 and IRF-2 may play an important role in the regulation of IFN-beta and IFN
      inducible genes and that IRF-2 may have dual functions as an activator and
      repressor in CNS-derived cells.

PMID- 9649119
TI  - Anti-proliferative activity and mechanism of action of titanocene dichloride.
AB  - Development of resistance to cytotoxic agents is a major limitation to their
      clinical use. Novel compounds are synthesized with a view to develop non-cross
      resistant, less toxic and more potent activity. The detection of the anti-tumour
      properties of the inorganic compound cisplatin stimulated a broad search for
      other metal-containing complexes. Titanocene dichloride was synthesized on this
      basis and has shown potent anti-neoplastic activity in experimental animals. We
      have examined the in vitro activity of titanocene dichloride in two pairs of
      platinum-sensitive and resistant human ovarian carcinoma cell lines, A2780/2780CP
      and CH1/CH1cisR, and in mutated p53- and bcl-2-transfected clones of A2780 cells.
      A time- and concentration-dependent anti-proliferative effect was observed in all
      cell lines treated with titanocene dichloride. The drug was found to
      significantly overcome platinum resistance in the 2780CP and the CH1 cisR cell
      lines and in the bcl-2 and the mutant p53 transfectants of A2780 cells.
      Titanocene dichloride induced a block in late S/early G2 phase of the cell cycle;
      however apoptotic cell death occurred from any phase of cycle. Titanium-DNA
      adducts were detected in A2780 cells treated with titanocene dichloride using
      atomic absorption spectrometry, suggesting that DNA may be a target for this
      drug. In agreement with this finding, p53 accumulated rapidly in drug-treated
      A2780 cells, indicative of a role for titanocene dichloride as a DNA-damaging
      agent. We have also performed studies to determine whether titanocene dichloride
      could demonstrate synergy with other cytotoxic agents in vitro. Isobologram
      analysis of cytotoxicity data obtained suggests that the combination of
      titanocene dichloride and 5-fluorouracil (5-FU) is synergistic. The potent in
      vivo anti-tumour activity of this compound, supported by the encouraging results
      from two phase I clinical trials, suggests that titanocene dichloride could be a
      promising novel chemotherapeutic agent.

PMID- 9649120
TI  - Interstitial photodynamic therapy with the second-generation photosensitizer
      bacteriochlorin a in a rat model for liver metastases.
AB  - Bacteriochlorin a (BCA) is a second-generation photosensitizer that is effective
      in tumour destruction upon illumination with light of a wavelength of 760 nm.
      Tissue penetration by light at this wavelength is greater compared with
      wavelengths at which commonly used photosensitizers are illuminated, making it
      possible to treat larger tumours. In a model of experimental liver metastases in
      rats, we measured lesion sizes after interstitial illumination of tumours at
      different times after intravenous administration of BCA (10 mg kg(-1)
      bodyweight), as well as BCA concentrations in liver and tumour tissue. In both,
      BCA concentrations showed a rapid decline within the first 4 h, followed by a
      slow decrease over the next 20 h, suggesting biphasic pharmacokinetics. No
      selective uptake in tumour tissue was observed. A near-linear relationship was
      found between lesion sizes and liver and tumour BCA concentrations, suggesting
      that optimal results with photodynamic therapy (PDT) could be obtained by
      illumination within a short time interval after administration, when tissue
      concentrations are highest. No severe liver toxicity was observed as indicated by
      serum ALAT levels. However, in all tumours evaluated, islands of vital-looking
      cells were present leading to tumour regrowth within 35 days. In view of the
      obtained lesion diameters of approximately 13 mm after BCA-PDT and the rapid
      clearance rate of BCA, the concept of a near-infrared absorbing photosensitizer
      for PDT of liver tumours is a potential interesting strategy.

PMID- 9649121
TI  - Electrochemotherapy on liver tumours in rabbits.
AB  - Electrochemotherapy (ECT) is a new therapeutic approach combining the effects of
      a low-permeant cytotoxic drug, bleomycin (BLM), administered i.v. and cell
      permeabilizing electric pulses (EPs) locally delivered to tumours. The transient
      permeabilization of the cell membrane by the EPs allows free access of BLM to its
      intracellular targets, largely enhancing BLM's cytotoxic effects. ECT efficacy
      has been proved so far on transplanted subcutaneous murine tumours and on
      subcutaneous metastases in humans. Here, we present the first study of the
      effects of ECT on tumours transplanted to livers in rabbits. We used a recently
      developed EP applicator consisting of an array of parallel and equidistant
      needles to be inserted in tissues. Effects of EPs alone or of ECT were assessed
      by histological analysis, tumour growth rates and survival of the treated
      animals. A transient blood hypoperfusion was seen in the electropulsed areas,
      with or without BLM, related to EP-dependent vasoconstriction but this had no
      major effects on cell survival. Long-term effects depended on the presence of BLM
      at the time of EP delivery. Almost complete tumour necrosis was observed after
      ECT, resulting from both BLM direct cytotoxic effects on electropermeabilized
      tumour cells and indirect effects on the tumour vessels. A large reduction in
      tumour growth rate and significantly longer survival times were scored in
      comparison with control rabbits. Moreover, ECT of liver tumours was well
      tolerated and devoid of systemic side-effects. When ECT was associated with a
      local interleukin 2-based immunotherapy, increased local anti-tumour
      effectiveness as well as a large decrease in the number of metastases were
      observed. Thus, ECT could become a novel treatment modality for liver tumours and
      other solid internal malignancies.

PMID- 9649122
TI  - Evaluation of a novel in vitro assay for assessing drug penetration into
      avascular regions of tumours.
AB  - The poor blood supply to solid tumours introduces many factors that affect the
      outcome of chemotherapy, one of which is the problem of drug delivery to poorly
      vascularized regions of tumours. Whereas poor drug penetration has been
      recognized as a contributing factor to the poor response of many solid tumours,
      the question of drug penetration through multicell layers has not been thoroughly
      addressed, largely because of restrictions imposed upon these studies by the
      requirement for either radiolabelled or naturally fluorescent compounds. The aim
      of this study is to describe modifications made to a recently published assay
      that broadens the scope for assessing drug penetration during the early stages of
      drug development and to characterize the ability of various drugs to penetrate
      multicell layers. DLD-1 human colon carcinoma cells were cultured on Transwell
      COL plastic inserts placed into 24-well culture plates so that a top and bottom
      chamber were established, the two chambers being separated by a microporous
      membrane. Drugs were added to the top chamber at doses equivalent to peak plasma
      concentrations in vivo and the rate of appearance of drugs in the bottom chamber
      determined by high-performance liquid chromatography (HPLC). Both 3-amino-1,2,4
      benzotriazine 1,4-dioxide (tirapazamine) and 7-[4'-(2-nitroimidazol-1-yl)-butyl]
      theophylline (NITP) rapidly penetrated DLD-1 multicell layers (50.9 +/- 12.1
      microm thick) with t(1/2) values of 1.36 and 2.38 h respectively, whereas the
      rate of penetration of 5-aziridino-3-hydroxymethyl-1-methyl-2-[1H-indole-4,7
      dione] prop-beta-en-alpha-ol (EO9) and doxorubicin through multicell layers was
      significantly slower (t(1/2) = 4.62 and 13.1 h respectively). Inclusion of
      dicoumarol increases the rate of EO9 penetration, whereas reducing the oxygen
      tension to 5% causes a reduction in tirapazamine penetration through multicell
      layers, suggesting that the extent of drug metabolism is one factor that
      determines the rate at which drugs penetrate multicell layers. The fact that EO9
      does not readily penetrate a multicell layer, in conjunction with its rapid
      elimination in vivo (t(1/2) < 10 min), suggests that EO9 is unlikely to penetrate
      more than a few microm from a blood vessel within its pharmacokinetic lifespan.
      These results suggest that the failure of EO9 in the clinic is due to a
      combination of poor drug penetration and rapid elimination in vivo.

PMID- 9649123
TI  - Differential expression of vascular endothelial growth factor mRNA vs protein
      isoform expression in human breast cancer and relationship to eIF-4E.
AB  - Angiogenesis is the formation of new blood vessels from the existing vasculature.
      Vascular endothelial growth factor (VEGF) is an endothelium-specific angiogenic
      factor strongly implicated in pathological angiogenesis. In this study, the mRNA
      and protein expression of the four alternatively spliced VEGF isoforms (121, 165,
      189 and 206 amino acids) were examined in normal and malignant breast tissues.
      Three VEGF transcripts were detected in both (121>165>189), whereas only VEGF165
      protein was detected. The tumours expressed more VEGF mRNA (P = 0.02) and protein
      (P < 0.0001), with eight-fold more VEGF protein generated per mRNA unit (P =
      0.009). To examine this further, the expression of eIF-4E, a translation
      initiation factor, was examined. Increased eIF-4E mRNA levels were detected in
      the tumours (P < 0.0001) that correlated with VEGF mRNA (P = 0.0002), implying co
      regulation of these genes. VEGF mRNA expression was elevated in tumours
      expressing the epidermal growth factor receptor (P < 0.01), but there was no
      difference according to oestrogen receptor status (P = 0.9), node status (P =
      0.09) or between differing histologies (P = 0.4). These data suggest that
      elevated VEGF protein expression, by both enhanced transcription and translation,
      is a potential means by which tumour angiogenesis is induced in breast
      carcinomas. VEGF expression is also significantly associated with factors
      correlating with a poor outcome, implying a role in progression of this disease.

PMID- 9649124
TI  - A sequential treatment regimen with melatonin and all-trans retinoic acid induces
      apoptosis in MCF-7 tumour cells.
AB  - Neoplastic events are marked by uncontrolled cell proliferation. One major focus
      of cancer research has been to identify treatments that reduce or inhibit cell
      growth. Over the years, various compounds, both naturally occurring and
      chemically synthesized, have been used to inhibit neoplastic cell proliferation.
      Two such oncostatic agents, melatonin and retinoic acid, have been shown to
      suppress the growth of hormone-responsive breast cancer. Currently, separate
      clinical protocols exist for the administration of retinoids and melatonin as
      adjuvant therapies for cancer. Using the oestrogen receptor (ER)-positive MCF-7
      human breast tumour cell line, our laboratory has studied the effects of a
      sequential treatment regimen of melatonin followed by all-trans retinoic acid
      (atRA) on breast tumour cell proliferation in vitro. Incubation of hormonally
      responsive MCF-7 and T47D cells with melatonin (10(-9) M) followed 24 h later by
      atRA (10(-9) M) resulted in the complete cessation of cell growth as well as a
      reduction in the number of cells to below the initial plating density. This
      cytocidal effect is in contrast to the growth-suppressive effects seen with
      either hormone alone. This regimen of melatonin followed by atRA induced
      cytocidal effects on MCF-7 cells by activating pathways leading to apoptosis
      (programmed cell death) as evidenced by decreased ER and Bcl-2 and increased Bax
      and transforming growth factor beta 1 (TGF-beta1) expression. Apoptosis was
      reflected morphologically by an increase in the number of lysosomal bodies and
      perinuclear chromatin condensation, cytoplasmic blebbing and the presence of
      apoptotic bodies. The apoptotic effect of this sequential treatment with
      melatonin and atRA appears to be both cell and regimen specific as (a) ER
      negative MDA-MB-231 and BT-20 breast tumour cells were unaffected, and (b) the
      simultaneous administration of melatonin and atRA was not associated with
      apoptosis in any of the breast cancer cell lines studied. Taken together, the
      results suggest that use of an appropriate regimen of melatonin and atRA should
      be considered for preclinical and clinical evaluation against ER-positive human
      breast cancer.

PMID- 9649125
TI  - Modulation of the insulin-like growth factor-I system by N-(4-hydroxyphenyl)
      retinamide in human breast cancer cell lines.
AB  - The potent mitogenic activity of insulin-like growth factor I (IGF-I) on breast
      epithelium is inhibited by retinoic acid in oestrogen receptor-positive (ER+)
      breast cancer cell lines. We studied and compared the effects of N-(4
      hydroxyphenyl)-retinamide (4-HPR) in terms of growth inhibition and modulation of
      the IGF-I system in ER+ (MCF-7) and oestrogen receptor-negative (ER-) (MDA-MB231)
      breast cancer cell lines. Treatment with 1-10 microM 4-HPR for up to 96 h induced
      a dose- and time-dependent inhibition of proliferation in both breast cancer cell
      lines. Induction of apoptosis was much more evident in MCF-7 than in MDA-MB231
      cells (30-40% compared with 0-5% respectively at 5 microM for 48 h). Exogenous
      human recombinant IGF-I (hr-IGF-I)-stimulated cell proliferation was abolished by
      1 microM 4-HPR in MCF-7 cells. Immunoreactive IGF-I-like protein concentration in
      conditioned medium was reduced by 38% in MCF-7 and by 90% in MDA-MB231 cell lines
      following treatment for 48 h with 5 microM 4-HPR. Western ligand blot analysis
      showed a reduction of IGF-binding protein 4 (BP4) and BP5 by 67% and 87%,
      respectively, in MCF-7, whereas IGF-BP4 and -BP1 were reduced by approximately
      20% in MDA-MB231 cells. Exposure to 5 microM 4-HPR for 48 h inhibited [125I]IGF-I
      binding and Scatchard analysis revealed a decrease of more than 50% in maximum
      binding capacity (Bmax) and a reduced receptor number/cell in both cancer cell
      lines. Steady-state type I IGF-receptor mRNA levels were reduced by approximately
      30% in both tumour cell lines. We conclude that 4-HPR induces a significant down
      regulation of the IGF-I system in both ER+ (MCF-7) and ER- (MDA-MB231) breast
      cancer cell lines. These findings suggest that, in our model, interference with
      the ER signalling pathway is not the only mechanism of breast cancer growth
      inhibition by 4-HPR.

PMID- 9649126
TI  - Mutations of the Apc gene in experimental colorectal carcinogenesis induced by
      azoxymethane in F344 rats.
AB  - We investigated in the rat the role of the Apc gene, which is mutated in familial
      adenomatous polyposis and sporadic colon cancer in the process leading from
      normal colonic mucosa to aberrant crypt foci (ACF) and finally to adenomas and
      adenocarcinomas. We analysed mutations in exon 15 of the rat Apc gene using in
      vitro synthesized protein assay in 66 ACF and in 28 colon tumours induced by
      azoxymethane. No Apc mutations were found in ACF, whereas five mutations were
      found in the tumours. The data suggest that mutations of the Apc gene are
      associated with the transition from ACF to adenoma and adenocarcinoma and not
      from normal mucosa to ACF.

PMID- 9649127
TI  - Low-level resistance to camptothecin in a human small-cell lung cancer cell line
      without reduction in DNA topoisomerase I or drug-induced cleavable complex
      formation.
AB  - To study the evolution of camptothecin (CPT) resistance, we have established two
      small-cell lung cancer cell lines with low (3.2-fold, NYH/CAM15) and high (18
      fold, NYH/CAM50) resistance to CPT by stepwise drug exposure. NYH/CAM50 cells had
      reduced topoisomerase I (topo I) content and activity, and consequently CPT
      induced DNA single strand breaks (SSBs) were reduced, as measured by alkaline
      elution. In contrast, NYH/CAM15 cells had identical topo I content and activity
      as compared with wild-type (wt) cells. CPT-mediated SSBs and the rate of their
      reversal after drug removal were also equal in wt and NYH/CAM15 cells, as were
      doubling time, the fraction of cells in S-phase and DNA synthesis rate in
      response to CPT. As the conversion of DNA SSBs to DNA double strand breaks (DSBs)
      is thought to represent a critical event leading to cell death, we measured DNA
      DSBs by neutral elution. In contrast to DNA SSBs, CPT induced fewer DNA DSBs in
      NYH/CAM15 than in wt cells. DNA flow cytometry showed that, in CPT-treated cells,
      the G1 phase was emptied as cells accumulated in late S- and G2M phase. A
      Spearman rank correlation showed that depletion of G1 and accumulation in late S
      and G2M correlated to CPT sensitivity in these three cell lines. In conclusion,
      acquired resistance to CPT can occur without a reduction in either topo I enzyme
      or CPT-induced cleavable complex formation, while a decrease in the level of CPT
      induced DNA DSBs may be of major importance in the early stages of CPT
      resistance.

PMID- 9649128
TI  - Paracrine effects of hepatocyte growth factor/scatter factor on non-small-cell
      lung carcinoma cell lines.
AB  - We have studied the mitogenic, motogenic and morphogenic effects of hepatocyte
      growth factor (HGF), also known as scatter factor (SF), on 15 non-small-cell lung
      carcinoma (NSCLC) cell lines that have had their ras genotype determined. HGF/SF
      stimulated proliferation in only three cell lines and exerted no mitogenic
      activity on six lines. The growth of the remaining six lines was inhibited. The
      mitogenic effects were not related to the ras genotype of these cell lines, but
      the inhibitory effect was more commonly observed in cell lines with relatively
      high levels of Met/HGF receptor (HGFR) expression. HGF/SF induced or enhanced
      both scatter activity on monolayer culture and single-cell invasion in collagen
      gels in approximately half of these cell lines. Although the ras genotype of
      tumour cells did not influence the HGF/SF-induced motogenic activity, cell lines
      with the mutant ras genotype more commonly demonstrated a spontaneous motogenic
      activity than those with the wild-type ras genotype. When tumour cells were grown
      in collagen gels, HGF/SF induced irregular branching extensions of cell
      aggregates formed by five out of eight adenocarcinoma cell lines, but significant
      lumen morphogenesis was distinctly absent. The presence of autocrine HGF/SF loop
      in these tumour cell lines did not influence their spontaneous or HGF/SF-induced
      mitogenic, motogenic or morphogenic activities. Overall, our data suggest that
      stimulation of cell motility, rather than proliferation or differentiation, is
      the predominant paracrine effect of HGF/SF on NSCLC cells in vitro.

PMID- 9649129
TI  - Determinants of CPT-11 and SN-38 activities in human lung cancer cells.
AB  - Irinotecan (CPT-11) is a semisynthetic camptothecin derivative with a broad
      spectrum of anti-tumour activity. Carboxylesterase (CE) catalyses the conversion
      of CPT-11 to SN-38 (7-ethyl-10-hydroxycamptothecin), the active form of CPT-11.
      The antiproliferative effects of CPT-11 and SN-38, CE-activity and topoisomerase
      I protein expression were investigated in five human small-cell lung cancer
      (SCLC) cell lines and four human non-small-cell lung cancer (NSCLC) cell lines.
      Antiproliferative activity, expressed as IC50 values, was determined using the
      MTT assay. CPT-11 was significantly more active in SCLC than in NSCLC cell lines
      (P = 0.0036), whereas no significant difference between histological types was
      observed with SN-38. A significant correlation (r2 = 0.52, P = 0.028) was
      observed between CE activity and chemosensitivity to CPT-11 but not to SN-38, and
      significantly higher CE activity was observed in SCLC compared with NSCLC cell
      lines (P = 0.025). Western blotting experiments showed topoisomerase I protein
      expressions within a factor of 2, and a granular nuclear staining was detectable
      in all cell lines by immunocytochemistry of cytospins. No correlation was
      observed between protein expression and sensitivity to CPT-11 or SN-38. Cellular
      and medium concentrations of CPT-11 and SN-38 were measured by high-performance
      liquid chromatography (HPLC) in one SCLC cell line with high CE activity and high
      sensitivity to CPT-11, and one NSCLC cell line with low sensitivity to CPT-11 and
      CE activity. Intracellular concentrations of CPT-11 and SN-38 were higher in the
      SCLC cell line, and this was associated with an increase in cellular uptake of
      CPT-11 compared with the medium, and an increased intracellular formation of SN
      38. In conclusion, CE activity appears to be associated with higher sensitivity
      to CPT-11 in human lung cancer cell lines and may partly explain the difference
      in the in vitro sensitivity to CPT-11 between SCLC and NSCLC cells. The
      assessment of CE activity in clinical material of lung cancer patients undergoing
      treatment with CPT-11 may be warranted. However, other mechanisms may influence
      sensitivity to CPT-11, possibly including drug transport.

PMID- 9649130
TI  - Telomerase activity in benign and malignant human thyroid tissues.
AB  - Telomerase is a specialized ribonucleoprotein polymerase that directs the
      synthesis of telomerase repeats at chromosome ends. Accumulating evidence has
      indicated that telomerase is stringently repressed in normal human somatic
      tissues but reactivated in cancers and immortal cells, suggesting that activation
      of telomerase activity plays a role in carcinogenesis and immortalization. In
      this work, the status of telomerase activity during the development of human
      thyroid cancer was determined using telomeric repeat amplification protocol
      (TRAP) in 14 nodular hyperplasia, 14 adenomas, 23 papillary carcinomas and 11
      follicular carcinomas. Positive telomerase activity was detected in 2 of 14
      nodular hyperplasias (14%), 4 of 14 adenomas (29%), 12 of 23 papillary carcinomas
      (52%) and 10 of 11 follicular carcinomas (91%). The cancers that are negative for
      telomerase activity are mostly in early stage (stage I or II). These results
      suggest that telomerase reactivation plays a role during the development of
      thyroid cancer.

PMID- 9649131
TI  - Chromosome instability is a predominant trait of fibroblasts from Li-Fraumeni
      families.
AB  - Previous work has indicated a role for p53 in cell cycle control, genomic
      stability and cellular responses to DNA-damaging agents. However, few data are
      available for human fibroblasts heterozygous for defined germline mutations in
      TP53. We report studies on 25 strains derived from 12 families with Li-Fraumeni
      syndrome (LFS) and 18 strains from normal volunteers. The families include three
      that are classical LFS families, but in whom no TP53 mutation has been found. In
      the families with mutations, increased longevity and resistance to low-dose-rate
      ionizing radiation showed a statistically significant association with the
      presence of TP53 mutations. However, not all heterozygotes had increased
      longevity or were radioresistant, and fibroblasts from cancer-affected members of
      LFS families without TP53 mutations showed no significant increase in either of
      these end points. In contrast, all mutation-carrying strains showed evidence of
      genomic instability, expressed as aneuploidy, and accumulated structural
      chromosome aberrations in up to 100% of cells, usually accompanied by loss of the
      wild-type TP53 allele, immediately before senescence. Levels of aneuploidy higher
      than in normal cells were also observed in fibroblasts from families without TP53
      mutations, suggesting that chromosome instability is a major factor in
      determining the cancer proneness of these families.

PMID- 9649132
TI  - Is chromosome 9 loss a marker of disease recurrence in transitional cell
      carcinoma of the urinary bladder?
AB  - Investigation of transitional cell carcinoma of the urinary bladder (TCC)
      patients classified by recurrence and/or progression has demonstrated that loss
      of chromosome 9, as detected by FISH analysis of the pericentromeric classical
      satellite marker at 9q12, occurs early. A total of 105 TCCs from 53 patients were
      analysed in situ by two independent observers for loss of chromosome 9 using
      quantitative fluorescence in situ hybridization (FISH). All 53 primary tumours
      were evaluated for chromosomes 9, 7 and 17. Normal ranges for chromosomal copy
      number were defined for normal skin epidermis and bladder epithelium. Values for
      chromosome 9 copy number outwith the range 1.51-2.10 (mean +/- 3 x s.d. of normal
      values) were significantly abnormal. Twenty-five TCCs were detected with
      consistent monosomic scores. Of 89 TCCs, in which multiple tumour areas were
      analysed, 85 tumours (96%) demonstrated the same chromosome 9 copy number in all
      areas (2-6) analysed; only three tumours demonstrated heterogeneity for this
      locus. A total of 36% (12 out of 33) of patients with subsequent disease
      recurrence demonstrated loss of chromosome 9 in their primary and all subsequent
      TCCs analysed. Only a single patient (n = 20) with non-recurrent TCC showed loss
      of chromosome 9 (P = 0.0085). Of 53 primary tumours, eight showed significant
      elevation of chromosome 17. Of these patients, six demonstrated elevation in
      chromosome 7 copy number. No abnormalities were observed in non-recurrent
      patients. This study describes rapid quantitation of chromosomal copy number by
      FISH using a pericentromeric probe for chromosome 9 in TCC of the urinary
      bladder. Routinely fixed and processed material was evaluated without
      disaggregation. Strict quality control of FISH demonstrated that this technique
      was reproducible in a clinical environment and could be used to detect genetic
      changes relevant to patient outcome. It is proposed that loss of chromosome 9
      from primary TCC of the urinary bladder identified patients at high risk of
      recurrence and possible progression.

PMID- 9649133
TI  - BRCA1 mutations in southern England.
AB  - If genetic testing for breast and ovarian cancer predisposition is to become
      available within a public health care system there needs to be a rational and
      cost-effective approach to mutation analysis. We have screened for BRCA1
      mutations in 230 women with breast cancer, all from the Wessex region of southern
      England, in order to establish the parameters on which to base a cost-effective
      regional mutation analysis strategy. Truncating mutations were detected in 10/155
      (6.5%) consecutive cases selected only for diagnosis under the age of 40 (nine of
      these ten women had a strong family history of breast or ovarian cancer), 3/61
      (4.9%) bilateral-breast cancer cases (all three mutations occurring among women
      for whom the first cancer was diagnosed under 40 years) and 8/30 (26.6%) breast
      cancer cases presenting to the genetics clinic (for whom a strong family history
      of breast and/or ovarian cancer was present). Ten different mutations were
      detected in 17 families, but three of these accounted for 10/17 (59%) of the
      families. The cost of screening the population for mutations in the entire BRCA1
      gene is unacceptably high. However, the cost of screening a carefully selected
      patient cohort is low, the risk of misinterpretation much less and the potential
      clinical benefits clearer.

PMID- 9649134
TI  - Increased microvessel density in mucinous compared with malignant serous and
      benign tumours of the ovary.
AB  - Microvessel density of benign, borderline and malignant ovarian tumours was
      studied immunohistochemically using antibodies to the endothelial cell markers
      CD31, CD34 and factor VIII-related antigen. Microvessel density was compared in
      tumours of different histological subtype, stage and patient outcome. CD31
      immunostained sections were examined and regions of high and average microvessel
      density were selected. Identical regions were located on CD34- and factor VIII
      related antigen-immunostained serial sections and microvessel counts obtained and
      converted to vessels mm(-2). CD31 and CD34 immunostaining revealed increased
      microvessel density in both the high and average vessel density regions of
      mucinous (222.4 +/- 24.8; 79.9 +/- 8.5) compared with serous (105.4 +/- 20.7;
      33.3 +/- 6.8) and benign (84.4 +/- 19.4; 20.4 +/- 4.4) tumours (P < 0.001). CD31
      and CD34 immunostaining also revealed increased microvessel density in early
      stage mucinous tumours (234.6 +/- 28.2; 87.8 +/- 9.2) compared with that observed
      in both early- (72.8 +/- 15; 12.9 +/- 2.4) and late- (115.6 +/- 26.5; 29.8 +/-
      8.5) stage serous tumours (P < 0.001). No differences in microvessel density in
      samples from patients with differing outcomes were observed (P > 0.05). Reduced
      factor VIII-related antigen compared with CD31 and CD34 immunostaining was
      observed in both borderline and malignant mucinous and serous tumours (P < 0.02)
      but not in benign tumours (P > 0.05). Our results contradict the putative
      association between increased microvessel density and poor prognosis and suggest
      that the level and control of angiogenesis may differ between ovarian tumour
      types.

PMID- 9649135
TI  - The luminescence immunoassay S-100: a sensitive test to measure circulating S
      100B: its prognostic value in malignant melanoma.
AB  - In this study we measured S-100B using a recently developed luminometric
      immunoassay with a detection limit of 0.02 microg l(-1). By measuring serum S
      100B concentrations in 58 apparently healthy individuals a reference value of
      0.16 microg l(-1) was found. To assess the sensitivity of the assay we measured
      levels of S-100B protein in the serum of 251 patients with cutaneous malignant
      melanoma before the start of treatment. Only one of 179 patients with limited
      disease had a serum concentration higher than the reference value, whereas
      elevated levels were seen in 79% of patients with metastasized disease. In the
      latter group the NSE serum concentration was elevated in 42%. Using a receiver
      operating characteristic (ROC) curve it is shown that S-100B is a significantly
      better parameter than neuron-specific enolase (NSE) for distinguishing patients
      with limited disease from those with extensive melanoma. Pretreatment S-100B
      values were highly predictive for the period of survival. Patients with limited
      disease have increased risk for early death with increasing levels of S-100B
      protein. Within the group of patients with positive lymph nodes and/or with
      distant metastases, elevated S-100B levels strongly identified high-risk
      patients. Our study indicates that the measurement of S-100B as a tumour marker
      in the management of patients with cutaneous malignant melanoma has clinical
      significance.

PMID- 9649136
TI  - Suppression of tumorigenic and metastatic potentials of human melanoma cell lines
      by mutated (143 Val-Ala) p53.
AB  - Metastatic melanoma, compared with other cancers, appears to be unusual because
      of its low frequency of p53 mutations and prevalence of wild-type p53 protein in
      advanced malignancy. Here, we examined the effects of wild-type and mutated p53
      (143 Val-Ala) on tumorigenic and metastatic potential of two human melanoma cell
      lines. The cell line UISO-MEL-4 contains wild-type p53 and is tumorigenic,
      whereas UISO-MEL-6 lacks p53 and produces lung and liver metastasis upon s.c.
      injection into athymic mice. Our study showed that UISO-MEL-4 stably transfected
      with wild-type p53 cDNA driven by cytomegalovirus promoter-enhancer sequences
      expressed high levels of p53 and p21 and formed s.c. tumours in vivo. Mutated p53
      (143 Val-Ala) expression, on the other hand, inhibited tumour growth in 50% of
      cases and produced significantly slower growing non-metastatic tumours. Reduced
      tumour growth involved necrotic as well as apoptotic cell death. Inhibition of
      tumour growth was abrogated by the addition of Matrigel (15 mg ml(-1)). With UISO
      MEL-6 cells, stably transfected with mutant p53, tumour growth was delayed and
      metastasis was inhibited. In soft agar colony formation assay, both wild-type and
      mutant p53 transfectants reduced anchorage-independent colony formation in vitro.
      These data suggest that mutated (143 Val-Ala) p53, which retains DNA binding and
      some of the transactivation functions of the wild-type p53 protein, suppresses
      tumorigenic and metastatic potentials of human melanoma cell lines in vivo.

PMID- 9649137
TI  - Comparative genomic hybridization and telomerase activity analysis identify two
      biologically different groups of 4s neuroblastomas.
AB  - Chromosomal aberrations of 20 stage 4s neuroblastomas were analysed by
      comparative genomic hybridization (CGH). In a subset of 13/20 tumours, telomerase
      activity was evaluated by the telomeric repeat amplification protocol (TRAP). The
      CGH data were compared with the CGH results of ten stage 1 and 2 (stage 1/2) and
      22 stage 3 and 4 (stage 3/4) neuroblastomas. A total of 17/20 stage 4s
      neuroblastomas did not progress clinically, whereas tumour progression with
      lethal outcome occurred in 3/20 cases. The CGH data of clinically non-progressing
      stage 4s tumours revealed a high rate of whole-chromosome aberrations (73.4%)
      with an overrepresentation of mainly chromosomes 2, 6, 7, 12, 13, 17, 18 and an
      underrepresentation of mainly chromosomes 3, 4, 11, 14. MYCN amplification or 1p
      deletion was observed in only 1/27 or 2/17 clinically non-progressing stage 4s
      tumours respectively, whereas all three progressive stage 4s neuroblastomas
      showed MYCN amplification, 1p deletion and, in 2/3 cases, distal 17q gains.
      Except for one case, telomerase activity was not observed in non-progressing
      stage 4s neuroblastomas. In contrast, 4s tumours with lethal outcome revealed
      elevated telomerase activity levels. Our data suggest that stage 4s
      neuroblastomas belong to two biologically different groups, one of which displays
      the genetic features of localized stage 1/2 tumours, whereas the other mimics
      advanced stage 3/4 neuroblastomas.

PMID- 9649138
TI  - Alterations of TP53 in microdissected transitional cell carcinoma of the human
      urinary bladder: high frequency of TP53 accumulation in the absence of detected
      mutations is associated with poor prognosis.
AB  - We have used microdissection of paraffin-embedded histological sections and
      polymerase chain reaction (PCR)-based direct DNA sequencing for 54 transitional
      cell carcinoma (TCC) of the bladder, to examine critically the association
      between TP53 nuclear accumulation determined by immunohistochemistry and the
      presence of TP53 mutations, and to examine their relationship to tumour stage and
      grade, as well as patient survival. There was a significant association between
      the presence of TP53-positive nuclei (> 10%) and a higher histological stage and
      grade (P = 0.0115, P = 0.0151 respectively; Fisher's exact). A significant
      association between TP53 gene mutations and TP53 nuclear reactivity in more than
      10% of tumour cell nuclei was also observed (P = 0.0003; Fisher's exact).
      Mutations were detected in 18/54 (33%) cases together with the wild-type sequence
      when analysed from bulk frozen samples, with significant clustering of mutations
      in exons 7 and 8. The microdissection method distinguished more clearly between
      heterozygous and/or homozygous alterations of the TP53 tumour-suppressor gene,
      and clearly showed frequent accumulation of TP53 in the absence of mutations.
      When microdissecting immunonegative regions from the same paraffin sections,
      three out of ten samples showed the identical mutations detected in the
      immunopositive regions. There was a significant association between TP53
      immunoreactivity in more than 50% of tumour cell nuclei and decreased survival
      among all patients (P = 0.0325; log-rank test). The patients with TP53 mutations
      showed a trend for a shorter survival period; however, the association was not
      statistically significant at the 95% confidence level (P = 0.132; log-rank test).
      In conclusion, our observations show that accumulation of TP53 occurs frequently
      in the absence of mutations, and that such accumulation is nevertheless
      associated with poor survival when it occurs in a high proportion (> 50%) of
      tumour cell nuclei.

PMID- 9649139
TI  - Expression of matrix metalloproteinases (MMP-1 and -2) and their inhibitors (TIMP
      1, -2 and -3) in oral lichen planus, dysplasia, squamous cell carcinoma and lymph
      node metastasis.
AB  - Although matrix metalloproteinases (MMPs) are among the potential key mediators
      of cancer invasion, their involvement in premalignant lesions and conditions is
      not clarified. Therefore, we studied, using in situ hybridization,
      immunohistochemistry and zymography the expression and distribution of MMP-1 and 
      2, and their tissue inhibitors (TIMPs -1, -2 and -3) in oral squamous cell
      carcinomas (SCC) and lymph node metastases as well as in oral lichen planus,
      epithelial dysplasias and normal buccal mucosa. In oral SCC and lymph node
      metastasis, MMP-1 mRNA was detected in fibroblastic cells of tumoral stroma. In
      two out of ten carcinomas studied, the peripheral cells of neoplastic islands
      were also positive. MMP-2 mRNA expression was noted in fibroblasts surrounding
      the carcinoma cells, and no signal in carcinoma cells was detected. A clear TIMP
      3 mRNA expression was seen in stromal cells surrounding the neoplastic islands in
      all SCCs and lymph node metastases studied. TIMP-1 mRNA was detected in some
      stromal cells surrounding the neoplastic islands, whereas the mRNA expression for
      TIMP-2 was negligible. On the other hand, expression of MMPs and TIMPs was
      consistently low in oral epithelial dysplasias, lichen planus and normal mucosa.
      In certain epithelial dysplasias and lichen planus, MMP-1 and -2 mRNA expressions
      were detected in few fibroblasts under the basement membrane zone, but normal
      mucosa was completely negative. In SCC and lymph node metastasis, a detectable
      immunostaining for MMP-1 in stromal cells and in some carcinoma cells was
      observed. MMP-2 immunoreactivity was detected in the peripheral cell layer in
      neoplastic islands and in some fibroblast-like cells of tumoral stroma.
      Immunostaining for TIMP-3 was detected in stromal cells surrounding the
      neoplastic islands. A weak positive staining for TIMP-1 was located in tumoral
      stroma, whereas the immunostaining for TIMP-2 was negative. Using zymography,
      elevated levels of MMP-2 and MMP-9 were observed in carcinoma samples in
      comparison with lichen planus or normal oral mucosa. Our results indicate that
      the studied MMPs and TIMPs are clearly up-regulated during invasion in oral SCC.
      However, there was also a clear, although weak, up-regulation of the expression
      of the MMPs but not TIMPs in some of the lichen planus and dysplastic lesions.

PMID- 9649140
TI  - Association of tumour necrosis factor alpha and its receptors with thymidine
      phosphorylase expression in invasive breast carcinoma.
AB  - Angiogenesis is an essential requirement for tumour growth and metastasis and is
      regulated by a complex network of factors produced by both stromal cells and
      neoplastic cells within solid tumours. The cytokine tumour necrosis factor alpha
      (TNF-alpha) and the enzyme thymidine phosphorylase (TP) are two factors known to
      promote tumour angiogenesis. We have demonstrated recently that high numbers of
      tumour-associated macrophages (TAMs) are significantly associated with increased
      tumour angiogenesis and poor prognosis in invasive carcinoma of the breast. We
      have also shown that TAMs are a major source of TNF-alpha in invasive breast
      carcinomas, and that macrophage-like stromal cells as well as tumour cells
      synthesize TP in such tumours. However, little is known of the factors that
      regulate the production or activity of these factors in the tumour
      microenvironment. As TNF-alpha has been shown to up-regulate TP expression in
      tumour cells in vitro we performed an immunohistochemical study to investigate
      the possibility that TNF-alpha may be involved in the regulation of TP expression
      by malignant breast epithelial cells in vivo. To do this, we used a cocktail of
      non-neutralizing monoclonal anti-TNF-alpha antibodies to visualize both TNF-alpha
      expressing macrophages and TNF-alpha bound to its receptors on tumour cells and
      endothelial cells in a series of 93 invasive carcinomas of the breast. A
      semiquantitative grading system was then used to compare these staining patterns
      with that for TP in the same biopsies. TNF-alpha immunoreactivity was also
      compared with various important tumour variables known to relate to outcome in
      this disease (microvessel density, node status, grade, stage, receptor status and
      macrophage infiltration), as well as relapse-free and overall survival data for
      these patients. Our data show significant positive correlations between TNF-alpha
      bound to its receptors on tumour cells and: (1) TP protein production by tumour
      cells, and (2) axillary lymph node status (i.e. metastasis). These results
      suggest that tumour cell responsiveness to TNF-alpha produced by neighbouring
      TAMs may play a part in the regulation of TP expression by tumour cells as well
      as their metastatic behaviour. This may explain, in part, the relationship
      between increased macrophage infiltration and angiogenesis in breast cancer, and
      further supports the contention that TAMs may represent an important target for
      future anti-angiogenic therapies.

PMID- 9649141
TI  - Family history and survival in premenopausal breast cancer.
AB  - The clinicopathological characteristics of breast cancer in 95 women between the
      ages of 24 and 45 years with a family history of breast cancer were compared with
      tumours from 329 women with sporadic disease matched for age and year of
      diagnosis. There was a trend for the family history patients to have slightly
      smaller tumours (mean size 2.49 cm) than the controls (mean 3.04 cm) (Mann
      Whitney test, P = 0.09). A significantly greater proportion of the familial cases
      had grade III infiltrating ductal carcinoma than did the controls (40% vs 27%;
      chi2(1) = 5.64, P = 0.02). Despite this, there were more cases of operable node
      negative disease among the study group than among the controls (48% vs 32%;
      chi2(1) = 8.2, P = 0.004). There was a highly significant survival advantage for
      patients with a family history (chi2 = 22.4, P < 0.001). Five- and 10-year
      survival rates were 92% and 87% for those with a family history compared with 70%
      and 54% for those in the control group. This survival advantage was maintained
      when patients with operable disease only were considered. In multivariate
      analysis, which included age, tumour size, stage, histological grade and family
      history, family history was an independent predictor of favourable prognosis and,
      in a Cox model, was associated with a relative risk of survival of 6.11 (95% CI
      2.81-13.28). These results suggest that familial breast cancer has a more
      favourable clinical course than the more common sporadic forms of the disease.

PMID- 9649142
TI  - Doxorubicin vs epirubicin, report of a second-line randomized phase II/III study
      in advanced breast cancer. EORTC Breast Cancer Cooperative Group.
AB  - The EORTC Breast Cancer Cooperative Group carried out a randomized trial to
      compare doxorubicin with epirubicin as second-line chemotherapy in patients with
      metastatic breast cancer. Two hundred and fifty-nine patients with at least one
      site of metastatic disease entered this trial, of whom 232 patients were
      eligible. Treatment consisted of doxorubicin 75 mg m(-2) or epirubicin 90 mg m(
      2) i.v. every 3 weeks. The overall response rates for doxorubicin and epirubicin
      were 36% and 28% respectively (P = 0.173). The median time to progression was 23
      weeks for doxorubicin and 19 weeks for epirubicin (P = 0.063) and the median
      duration of response was 40 weeks for doxorubicin and 32 weeks for epirubicin (P
      = 0.059). The median survival was 47 weeks for doxorubicin and 44 weeks for
      epirubicin (P = 0.196). Leucocyte count on retreatment day (P = 0.011) and
      platelet nadir (P = 0.031) were significantly lower in the doxorubicin-treated
      group. Also mucositis (P < 0.001), diarrhoea (P = 0.005) and haemorrhage (P =
      0.048) were significantly worse in the doxorubicin arm. Nine patients on
      doxorubicin and two patients on epirubicin experienced congestive heart failure
      (CHF). At the dose levels used in this study, no statistical differences in
      response rate and survival were found between the two treatment arms. Treatment
      with doxorubicin tended to result in a slightly longer duration of response and
      time to progression but doxorubicin was more toxic than epirubicin.

PMID- 9649143
TI  - Tamoxifen reduces plasma homocysteine levels in healthy women.
AB  - Treatment with tamoxifen is associated with reduced incidence of myocardial
      infarction. As plasma homocysteine is an independent risk factor for
      cardiovascular disease, we studied the effects of tamoxifen on plasma
      homocysteine in 66 healthy women participating in the Italian prevention trial of
      breast cancer who were randomized in a double-blind manner to tamoxifen 20 mg
      day(-1) or placebo for 5 years. They were aged between 35 and 70 years, had
      undergone previous hysterectomy for non-malignant conditions and had no
      contraindications to the use of tamoxifen. Plasma levels of total homocysteine
      (tHcy) were measured at randomization and after 2 and 6 months. The mean +/- s.d.
      plasma levels of tHcy were 7.59 +/- 1.71 micromol l(-1), 7.25 +/- 1.61 and 7.09
      +/- 1.33 in the tamoxifen group and 8.07 +/- 2.06, 7.93 +/- 1.77 and 8.12 +/-
      2.04 in the placebo group at 0, 2 and 6 months (P = 0.008 for the between-group
      difference over time). The higher the baseline tHcy level, the greater was the
      lowering effect of tamoxifen. No statistically significant effect of age, body
      mass index or smoking habit on baseline tHcy levels and its variation over time
      was found. In conclusion, tamoxifen (20 mg day(-1) for 6 months) decreased plasma
      tHcy levels in healthy women. This effect may contribute to its protective effect
      on myocardial infarction.

PMID- 9649144
TI  - Predictive value of topoisomerase IIalpha and other prognostic factors for
      epirubicin chemotherapy in advanced breast cancer.
AB  - Although cytotoxic chemotherapy is widely used in advanced breast cancer, there
      are no powerful predictors for the therapy response. Because topoisomerase
      IIalpha (Topo IIalpha) is the molecular target for the anthracycline class of
      anti-cancer drugs, we compared the immunocytochemical assay of Topo IIalpha with
      other biomarkers in the prediction of clinical response to Topo II inhibitor
      chemotherapy. Fifty-five patients with advanced breast cancer were treated with a
      single cytotoxic drug, Topo II-inhibitor, epirubicin (30 mg m(-2) weekly up to
      1000 mg m(-2)), as first line cytotoxic chemotherapy. Objective response to
      treatment was analysed according to UICC criteria. The predictive value of Topo
      IIalpha expression, c-erbB2 oncoprotein, p53 tumour-suppressor protein, oestrogen
      (ER) and progesterone receptor (PR), S-phase fraction and DNA ploidy were
      analysed from representative formalin-fixed paraffin-embedded primary tumour
      samples. The proportion of Topo IIalpha-positive cells (Topo IIalpha index)
      failed to predict response to epirubicin therapy. Mean Topo IIalpha scores in 29
      responding patients were similar when compared with those with no change in
      disease progression (n = 13) and those with progressive disease (n = 13) (14.9%
      +/- 11.4% vs 15.5% +/- 7.6% vs 17.3% +/- 13.2%, not significant). Among the other
      biomarkers tested, overexpression of c-erbB2 oncoprotein and hormone receptor
      negativity were significantly associated with poor response. Response rate in
      patients with c-erbB2-overexpressing tumours was 32% compared with 65% in
      patients with no c-erbB2 overexpression (P = 0.0058). Accordingly, the response
      rate for ER-positive patients was 67% compared with 26% in ER-negative patients
      (P = 0.0021). Although both negative ER status and c-erbB2 overexpression are
      associated with high Topo IIalpha expression in breast cancer, step-wise logistic
      regression analysis showed that ER and c-erbB2 were associated with therapy
      response independent of Topo IIalpha expression. Histological grade, p53, DNA
      ploidy, tumour proliferation rate (S-phase fraction), stage of the disease at
      diagnosis, age of the patient, previous anti-oestrogen therapy or site of
      metastasis did not predict the response to epirubicin therapy. In conclusion,
      despite extensive in vitro evidence, expression of Topo IIalpha is unlikely to
      predict the response to Topo II inhibitor chemotherapy in advanced breast cancer.
      Among the prognostic biomarkers, overexpression of c-erbB2 oncogene and negative
      ER may have predictive value in epirubicin therapy in patients with advanced
      breast cancer.

PMID- 9649145
TI  - VLA2 integrin expression in breast carcinomas evaluated by automated and
      quantitative immunohistochemistry.
AB  - VLA2 is thought to be involved in the metastatic process in malignant tumours, in
      particular in carcinomatous cell adhesion to vessel basement membrane. VLA2
      expression was immunohistochemically investigated in 204 breast carcinomas.
      Frozen tissue sections were probed with monoclonal anti-VLA2 using automated
      (Ventana ES 320 System) and quantitative (SAMBA 2005 image processor)
      immunoperoxidase. A positive anti-VLA2 immunoreaction was observed in 48 tumours
      (23.5%), within epithelial carcinomatous cells. The VLA2-positive surface in
      tumours varied from 3% to 20% (mean 8.75, S.D. 7.17) and was correlated with
      histoprognostic indicators and tumour expression of various antigens detected
      using the same method as that for VLA2. The results show that VLA2
      immunoexpression was independent of the tumour size, grade, type and aneuploidy,
      and of the nodal status. VLA2 significantly correlated with ELAM, VCAM, VLA3 and
      P-glycoprotein (P-gp) (P < 0.01) and inversely correlated with cathepsin D (P <
      0.001), but was independent of Ki67/MIB1, p53, bcl-2, c-erbB-2, E cadherin,
      CD44v, CD31, oestrogen and progesterone receptors' (ER, PR) antigenic sites and
      pS2. The exact role, if any, of VLA2 in tumour cell dissemination remains to be
      elucidated and the clinical relevance of VLA2 immunodetection in breast
      carcinomas requires further investigation of the correlation between VLA2
      immunocytochemical expression and patients' outcome and response to chemotherapy.

PMID- 9649146
TI  - Improved cure rate in children with B-cell acute lymphoblastic leukaemia (B-ALL)
      and stage IV B-cell non-Hodgkin's lymphoma (B-NHL)--results of the UKCCSG 9003
      protocol.
AB  - From June 1990 to February 1996, 35 patients with B-cell acute lymphoblastic
      leukaemia (B-ALL) 13 of whom had CNS disease and 28 patients with stage IV B-cell
      non-Hodgkin's lymphoma (B-NHL) 22 of whom had CNS involvement were treated with a
      short, intensive multiagent chemotherapy regimen (UKCCSG 9003 protocol) based on
      the French LMB 86 regimen. Fifty-five were boys. The age range was 11 months to
      16.5 years (median 8.4 years). Chemotherapy included cyclophosphamide,
      vincristine, daunorubicin, high-dose methotrexate (COPADM) and etoposide/high
      dose cytarabine (CYVE) with frequent intrathecal (i.t.) triple therapy
      (methotrexate, cytarabine and hydrocortisone). Cranial irradiation (24 Gy in 15
      fractions) was recommended in patients with overt CNS disease. One patient with
      Wiskott-Aldrich syndrome was withdrawn after entry and has been excluded from the
      analysis. Ten patients (16%) have relapsed (CNS, four; BM, two; combined CNS and
      BM, three; and jaw, one) 4-11 months after diagnosis and two patients never
      achieved complete remission (CR). All have died. In seven of the patients who
      relapsed, treatment had been modified or delayed because of poor clinical
      condition. Seven patients (11%) died of toxicity 11 days to 4 months after
      diagnosis. The cause of death was sepsis (n = 5) or sepsis with renal failure (n
      = 2). With a median follow-up of 3.1 years from diagnosis (range 9 months to 6.3
      years), 43 patients (69%) survive in CR. This study confirms the effectiveness of
      this regimen with regard to the relapse rate (16%), although the rate of toxic
      death is of concern.

PMID- 9649147
TI  - Pulmonary toxicity after granulocyte colony-stimulating factor-combined
      chemotherapy for non-Hodgkin's lymphoma.
AB  - Sporadic cases have developed pulmonary toxicity after receiving chemotherapy and
      granulocyte colony-stimulating factor (G-CSF). However, because such cases
      received chemotherapy that alone frequently causes pulmonary toxicity, the role
      of G-CSF in this toxicity has been unclear. CHOP therapy (cyclophosphamide,
      doxorubicin, vincristine and prednisolone) only slightly induces pulmonary
      toxicity. However, we observed a considerable incidence of this toxicity in non
      Hodgkin's lymphoma subjects receiving CHOP therapy and G-CSF (6 out of 52
      subjects, 11.5%). In this cohort, among various characteristics, including the
      dose and interval of CHOP therapy, only the mean peak leucocyte count (MPLC) with
      each therapy cycle was associated with development of this toxicity (MPLC > or =
      23.0 x 10(9) l(-1), 6 out of 29 cases; MPLC < 23.0 x 10(9) l(-1), 0 out of 23
      cases; P = 0.020). These findings suggest that the effect of G-CSF is the main
      determinant of the pulmonary toxicity in these cases. Because the toxicity was
      associated with a large MPLC and did not recur in cases readministered G-CSF, an
      idiosyncratic reaction to G-CSF is unlikely to be the pathogenesis of this
      toxicity. Thus, lowering the G-CSF dose seems to be useful in the prevention of
      this toxicity. In all six cases, the time course of manifestation of the toxicity
      was the same, and early application of high-dose corticosteroid led to cure. This
      knowledge will be helpful in the care of similar cases.

PMID- 9649148
TI  - Early stem cell transplantation for chronic lymphocytic leukaemia: a chance for
      cure?
AB  - B-cell chronic lymphocytic leukaemia (CLL) cannot be cured by conventional
      therapy. To improve the prognosis of patients with CLL, we have designed a
      sequential treatment strategy that comprises intensive chemotherapy for
      mobilization of peripheral blood progenitor cells (PBPCs) and induction of
      minimal disease, followed by high-dose radiochemotherapy with stem cell
      reinfusion and post-transplant molecular monitoring by polymerase chain reaction
      (PCR) amplification of the complementary determining region III (CDRIII) gene. In
      a prospective study, we have evaluated this protocol in 18 patients with CLL,
      also including early stages of the disease. The median age was 49 (29-61) years;
      Binet stages were A, six; B, nine; and C, three. Adverse prognostic factors [high
      lymphocyte count and/or diffuse bone marrow (BM) infiltration] were present in 16
      out of 18 patients. All patients showed a clone-specific molecular marker as
      demonstrated by PCR amplification of CDRIII rearrangements. For stem cell
      mobilization and reduction of tumour load, one to two cycles of Dexa-BEAM
      chemotherapy were administered, resulting in minimal disease (circulating
      lymphoma cells <1 x 10(9) l(-1); BM infiltration <20%; lymphomas <2 cm) in 16 out
      of 18 patients, including four patients who already had minimal disease before
      Dexa-BEAM. Stem cell harvesting was successful in 14 patients. All grafts [three
      BM, 11 peripheral blood (PB)] were purged from leukaemic cells using
      immunomagnetic methods. Thirteen patients having achieved minimal disease were
      reinfused with purged autologous stem cells (ASC) after preparation with total
      body irradiation and cyclophosphamide. Engraftment was delayed in patients
      receiving BM (n = 3) but prompt [neutrophils >0.5 x 10(9) l(-1) after 10 (9-13)
      days, platelets >20 x 10(9) l(-1) after 11 (9-214) days] in patients restored
      with PBPCs (n = 10). Procedure-related deaths did not occur. Although the results
      of CDRIII PCR suggest persistence or recurrence of the leukaemic clone in at
      least three cases, to date only one patient has relapsed, whereas all others
      survive without clinical evidence of disease with a maximum follow-up of 48
      months. We conclude that sequential high-dose therapy using Dexa-BEAM and
      autologous stem cell transplantation is a safe and highly effective treatment for
      patients with CLL. However, a longer follow-up is needed to assess whether
      definite cures can be achieved using this strategy.

PMID- 9649149
TI  - Combined analysis of differentiation inhibitory factor nm23-H1 and nm23-H2 as
      prognostic factors in acute myeloid leukaemia.
AB  - Differentiation inhibitory factor (nm23 protein) inhibited the induction of the
      differentiation of various leukaemic cell lines. We previously reported that nm23
      genes (H1 and H2) were overexpressed in acute myelogenous leukaemia (AML) and
      nm23-H1 expression predicted the prognosis of AML, especially AML-M5. To clarify
      the correlation between French-American-British (FAB) classification and nm23
      expression level and to clarify the involvement of nm23-H2 and nm23-H1 in patient
      survival, we investigated the relative levels of nm23-H1 and -H2 mRNA in 76 AML
      samples using the reverse transcriptase-polymerase chain reaction. We confirmed
      that the expression of both nm23-H1 and -H2 genes in AML samples from three
      different hospitals was significantly higher than that in normal blood cells (P <
      0.0005). Overexpression of nm23-H1 was observed in each FAB AML-M1, -M2, -M3, -M4
      or -M5 subtype, and the predictive effect of nm23-H1 expression on AML prognosis
      was shown in FAB AML-M2 and -M5 cases. Although overexpression of nm23-H2 was
      also found in each FAB subtype, the expression of nm23-H2 in AML-M1 and -M3 cells
      was not significantly higher than that in normal cells. Among AML subtypes, AML
      M3 showed the lowest expression levels of both nm23 genes. To understand the
      relationship between nm23-H1 and -H2 expression levels, nm23 expression levels
      for all the AML cases were plotted and divided into four groups (group A, nm23-H1
      and -H2 both high; B, both low; C, only nm23-H1 high; D, only nm23-H2 high). A
      statistically significant correlation between the levels of expression of nm23-H1
      and -H2 was observed (r= 0.726). Most AML-M3 cases belonged to group B, but not
      other types of AML. Analysis of survival probability between the groups showed
      that group B survived for significantly longer compared with group A.
      Furthermore, AML-M3 cases survived for significantly longer compared with non-M3
      cases in the same group B. These data suggest that low expression levels of both
      nm23-H1 and -H2 are associated with good prognosis in AML patients.

PMID- 9649150
TI  - High-dose cyclosporin with etoposide--toxicity and pharmacokinetic interaction in
      children with solid tumours.
AB  - The tolerability, anti-tumour activity and pharmacokinetic interaction of high
      dose intravenous cyclosporin combined with intravenous etoposide was evaluated in
      children. Eighteen patients with recurrent or refractory tumours, all of whom had
      previously received etoposide, were treated with a combination of high-dose
      cyclosporin and etoposide. In 13, cyclosporin was given as a continuous infusion
      (15 mg kg(-1) per 24 h for 60 h) and in five a short 3-hour infusion of 30 mg kg(
      1) day(-1) on three consecutive days. Pharmacokinetic profiles of etoposide were
      determined with and without cyclosporin. Cyclosporin levels ranged from 1359 to
      4835 ng ml(-1) and cyclosporin increased the median area under the concentration
      time for etoposide curve from 7.2 to 12.5 mg ml(-1) min. The major toxicity was
      acute with varying forms of hypersensitivity reactions. In four cases this was
      severe. Hyperbilirubinaemia was present in 25 of 32 courses but was of short
      duration. In 14 courses, creatinine and/or urea was elevated, but was also
      transient. Significant hypertension was seen in six courses. Four of 17 patients
      evaluable for response obtained a partial response and one showed stable disease.
      It is concluded that in children given the combination of high-dose cyclosporin
      and etoposide, the etoposide dose should be halved in order to achieve an area
      under the drug concentration-time curve similar to that with etoposide alone. A
      continuous infusion schedule of cyclosporin is better tolerated during the period
      of administration but is associated with similar hepatic and renal dysfunction to
      a short schedule. The 24% response rate in children who had previously received
      etoposide suggests that this may be an effective method of enhancing drug
      sensitivity and further phase II evaluation is justified.

PMID- 9649151
TI  - Unresectable localized neuroblastoma: improved survival after primary
      chemotherapy including carboplatin-etoposide. Neuroblastoma Study Group of the
      Societe Francaise d'Oncologie Pediatrique (SFOP).
AB  - Neuroblastomas (NBs) were assessed according to INSS recommendations including
      MIBG scan and extensive bone marrow staging to eliminate metastatic spread.
      Patients with unresectable tumour received primary chemotherapy including two
      courses of carboplatin-etoposide (CE) and two of vincristine-cyclophosphamide
      doxorubicin (CAdO). Post-operative treatment was to be given only in children
      over 1 year of age at diagnosis who had residual disease or lymph node (LN)
      involvement. Between 1990 and 1994, 130 consecutive children were registered. In
      comparison with resectable primaries, these tumours were more commonly abdominal,
      larger and associated with N-myc amplification (NMA). Complete, very good and
      partial response (CR, VGPR, PR) to CE were, respectively, 1%, 7% and 44%, overall
      response rate (RR) to two courses of CE and two courses of CAdO was 71%, and the
      tumour could be removed in all but four of the children. The toxicity was
      manageable. The 5-year overall survival (OS) and event-free survival (EFS) were,
      respectively, 88% and 78% with a median follow-up of 38 months. In multivariate
      analysis, only NMA and LN involvement adversely influenced the outcome,
      particularly NMA. Children with unresectable NBs and no NMA fared as well as
      children with resectable ones as OS were, respectively, 95% and 99% and EFS 89%
      and 91%. Our data show encouraging results in localized but unresectable NBs as
      90% of children may be considered as definitely cured, especially those without
      NMA.

PMID- 9649152
TI  - A study of the feasibility and accuracy of pharmacokinetically guided etoposide
      dosing in children.
AB  - Pharmacokinetically guided dosing was performed in nine paediatric patients
      receiving etoposide. Doses on day 2 of a 2- or 3-day schedule were adapted on the
      basis of the day-1 area under the plasma etoposide concentration vs time curve
      (AUC). The day-1 AUC was estimated using a limited sampling model and the day-2
      target AUC defined by the etoposide dose-AUC relationship observed in 33
      children. Target AUC values (4.6-8.2 mg ml(-1) x min) were achieved with a high
      degree of precision and with little bias (mean error 11% and root mean squared
      error 15% respectively). Pharmacokinetic parameters were similar to those
      reported previously in children, although interpatient pharmacokinetic
      variability was less than that observed previously: plasma clearance, 23 (18-26)
      ml min(-1) m(-2); volume of distribution at steady state (Vdss), 6.0 (3.9-8.9) l
      m(-2); t(1/2) 254 (127-550) min (median and range). This study has demonstrated
      that pharmacokinetically guided dosing with etoposide is feasible. However,
      pharmacokinetically guided dosing is likely to be of most benefit in patients
      with abnormalities of renal or hepatic function, or in children with prior
      exposure to cisplatin.

PMID- 9649153
TI  - Dose escalation with repeated intrathecal injections of 131I-labelled MAbs for
      the treatment of central nervous system malignancies.
AB  - We have previously demonstrated a 33% response rate in patients with primitive
      neurectodermal tumours after the direct injection of 131I-monoclonal antibodies
      (MAbs) into the cerebrospinal fluid (CSF). Dose-limiting toxicity is
      myelosuppression due to the passage of the radioimmunoconjugate from the CSF to
      the blood compartment. This occurs at doses of 2220 MBq of 131I-MAb and above,
      although this is not seen in all patients studied and appears to be related to
      the degree of prior therapy received. Rather than attempting to improve the
      efficacy of this approach to the treatment of disseminated disease within the CSF
      compartment by dose escalation and haemopoietic rescue, we have explored the
      possibility of repeatedly administering the radioimmunoconjugate. Eight patients
      were recruited to the study, two of whom received two and six of whom received
      three injections of 131I-MAb. After repeated administration of 131I-MAb
      pharmacokinetic data revealed that, with one exception, the radioimmunoconjugate
      cleared from the CSF compartment with similar kinetics, while its residence time
      in the blood decreased with each injection. This was due to the development of an
      anti-mouse Ig response in the blood. Clearance of 131I-MAb from the ventricular
      CSF appears to be independent of the presence of an anti-mouse Ig response in
      this compartment. The differential clearance of the radioimmunoconjugate from the
      ventricular CSF and from the blood results in a marked increase in the
      therapeutic index that can be achieved. Up to 5920 MBq of 131I-MAb was
      administered as the third injection of radioimmunoconjugate and combined doses of
      up to 12,500 MBq were given without either haematological or neurological
      toxicity. These data illustrate that dose escalation and thus an increase in the
      dose rate delivered to tumour cells within the CSF is possible if ways are found
      to reduce the residence time of the radioimmunoconjugate in the blood
      compartment. Suggestions as to how this can best be achieved are reviewed in
      detail.

PMID- 9649154
TI  - Demonstration of increased collagen synthesis in irradiated human skin in vivo.
AB  - Fibrosis is a common side-effect of radiation therapy. As a complex network of
      cytokines and other mediators plays a central role in the process leading to
      fibrosis, we used an in vivo method to measure skin collagen synthesis, taking
      into account the physiological conditions. We determined suction blister (i.e.
      interstitial) fluid concentrations of types I and III procollagen propeptides,
      reflecting types I and III collagen synthesis, in irradiated and unirradiated
      skin of breast cancer patients 1-5 years after surgery and radiation therapy,
      hence using the patients as their own controls. The mean concentrations of the
      measured collagen markers were approximately two times higher in the irradiated
      skin than in the unirradiated contralateral breast skin. The difference slowly
      diminishes with time. These results indicate that abundant collagen synthesis in
      the irradiated skin continues several years after discontinuation of the
      radiation therapy, leading to fibrosis. The method outlined here offers a new in
      vivo perspective to study events leading to radiation fibrosis.

PMID- 9649155
TI  - Effective treatment of cutaneous and subcutaneous malignant tumours by
      electrochemotherapy.
AB  - Electrochemotherapy (ECT) enhances the effectiveness of chemotherapeutic agents
      by administering the drug in combination with short intense electric pulses. ECT
      is effective because electric pulses permeabilize tumour cell membranes and allow
      non-permeant drugs, such as bleomycin, to enter the cells. The aim of this study
      was to demonstrate the anti-tumour effectiveness of ECT with bleomycin on
      cutaneous and subcutaneous tumours. This article summarizes results obtained in
      independent clinical trials performed by five cancer centres. A total of 291
      cutaneous or subcutaneous tumours of basal cell carcinoma (32), malignant
      melanoma (142), adenocarcinoma (30) and head and neck squamous cell carcinoma
      (87) were treated in 50 patients. Short and intense electric pulses were applied
      to tumours percutaneously after intravenous or intratumour administration of
      bleomycin. The tumours were measured and the response to the treatment evaluated
      30 days after the treatment. Objective responses were obtained in 233 (85.3%) of
      the 273 evaluable tumours that were treated with ECT. Clinical complete responses
      were achieved in 154 (56.4%) tumours, and partial responses were observed in 79
      (28.9%) tumours. The application of electric pulses to the patients was safe and
      well tolerated. An instantaneous contraction of the underlying muscles was
      noticed. Minimal adverse side-effects were observed. ECT was shown to be an
      effective local treatment. ECT was effective regardless of the histological type
      of the tumour. Therefore, ECT offers an approach to the treatment of cutaneous
      and subcutaneous tumours in patients with minimal adverse side-effects and with a
      high response rate.

PMID- 9649156
TI  - Aberrant crypt foci in patients with colorectal cancer.
AB  - Aberrant crypt foci (ACF) are clusters of abnormally large colonic crypts
      identified on the mucosal surface of the human colon. They are thought to be
      preneoplastic lesions. The aim of the present study was to compare density
      (number of ACF per square cm of mucosal surface), crypt multiplicity (number of
      crypts per ACF) and histology of ACF in colonic resections of colorectal cancer
      patients resident in two Italian provinces with a twofold difference in
      colorectal cancer incidence rates. Thirty-two and 26 colonic resections were
      collected after operation in Ragusa (Southern Italy) and Modena (Northern Italy),
      respectively, and fixed in 10% formalin. Mucosal layers were observed under a
      light microscope at 25x after staining with methylene blue. Density of ACF was
      significantly higher in Modena (median 0.101 ACF cm(-2)) than in Ragusa (0.049, P
      = 0.001), whereas there was no difference in crypt multiplicity. ACF were
      classified into three groups according to histological features: ACF with mild
      alterations (hypertrophic ACF, 73%), ACF with hyperplasia (hyperplastic ACF, 17%)
      and ACF with dysplasia (microadenomas, 10%). The proportions of ACF in the three
      groups were similar in the two provinces. Density of ACF was higher and crypt
      multiplicity lower proceeding from proximal to distal large bowel. Microadenomas
      were observed only in the colon, whereas hyperplastic ACF were more frequent in
      the rectum. In conclusion, density of ACF correlates with colorectal cancer rates
      in two Italian provinces, and shows a positive gradient from proximal to distal
      large bowel. Histology of ACF suggests that they may be precursors of both
      hyperplastic and adenomatous polyps. These data provide further evidence of the
      role of ACF in human colorectal carcinogenesis.

PMID- 9649157
TI  - Moderate amplifications of the c-myc gene correlate with molecular and
      clinicopathological parameters in colorectal cancer.
AB  - C-myc gene activation is a common event in multiple types of neoplasia and has
      been associated with different cellular processes relevant to the malignant
      transformation of cancer cells. C-myc gene amplification has been analysed in
      colorectal carcinomas by means of an innovative DNA fingerprinting method based
      on the arbitrarily primed PCR. This method requires a low amount of DNA, uses
      multiple internal controls and appears sensitive and reproducible.
      Clinicopathological and molecular correlates have been investigated in a series
      of 70 colorectal carcinomas. The incidence of c-myc amplification was 26%,
      ranging from two- to fivefold increase in copy number. C-myc amplification
      occurrence was more frequent in more advanced stages of tumour invasion (P <
      0.001) and was associated with mutations in the p53 tumour-suppressor gene (P =
      0.048). The presence of c-myc amplification was indicative of a shorter disease
      free survival period but, because of its strong association with Dukes' stage,
      its prognostic value is questionable.

PMID- 9649158
TI  - Plasma levels of tumour necrosis factor and its soluble receptors correlate with
      clinical features and outcome of Hodgkin's disease patients.
AB  - A prospective study was performed to assess the use of plasma measurement of
      tumour necrosis factor (TNF), lymphotoxin alpha (LT alpha) and their soluble
      receptors (p55 and p75) for prognostic risk assignment in 61 patients with
      Hodgkin's disease. Plasma levels of TNF, p55 and p75, but not of LT alpha, were
      higher in Hodgkin's disease patients than in healthy controls. Plasma levels of
      TNF, p55 and p75 were associated with several prognostic factors for Hodgkin's
      disease, including those related to the host (age, performance status) and to the
      tumour (disease stage, extranodal site involvement, bulky tumour, serum levels of
      LDH and beta2-microglobulin, histology). Elevated plasma levels of TNF, p55 and
      p75 were also associated with several parameters reflecting an immune activation,
      including the presence of B symptoms, elevated serum levels of gammaglobulins,
      alkaline phosphatase and fibrinogen, as well as peripheral monocytosis, anaemia
      and low serum albumin levels. Finally, elevated TNF ligand receptor plasma
      markers were associated with a lower incidence of complete response to therapy
      and predicted shorter free-from-progression survival and overall survival of the
      patients. These results indicate that the plasma levels of TNF and its soluble
      receptors correlate with clinical features and outcome of patients with Hodgkin's
      disease.

PMID- 9649159
TI  - A phase I/II study of multicyclic dose-intensive chemotherapy supported with G
      CSF, or G-CSF and haematopoietic progenitor cells in whole blood, in two
      consecutive cohorts of patients.
AB  - We investigated the reconstitutive potential of haematopoietic progenitor cells
      collected in autologous whole blood during multicycle dose-intensified
      chemotherapy. Forty patients with metastatic solid tumours were treated with up
      to six cycles of cisplatin and escalating doses of ifosfamide every 14 days.
      Cisplatin was administered in 3% sodium chloride over 3 h, followed by ifosfamide
      over 24 h and mesna over 36 h. The first cohort of patients received granulocyte
      colony-stimulating factor (G-CSF) days 4-14. Once dose-limiting toxicity was
      reached in cohort 1, the study continued with a second cohort of patients, in
      whom, in addition to G-CSF on days 4-14, 500 ml of G-CSF and chemotherapy
      'primed' whole blood was collected on day 15, i.e. on day 1 of treatment cycles
      two to six, before cisplatin administration. This volume of blood was kept
      unprocessed at 4 degrees C and reinfused 20-24 h after the completion of
      ifosfamide. In cohort 1, dose-limiting toxicity (DLT) was reached at ifosfamide
      6.0 g m(-2) with two out of six of the patients developing neutropenic fever.
      Although in cohort 2 no neutropenic fever was encountered, neither the frequency
      nor the duration of grade 4 neutropenia and thrombocytopenia were reduced.
      Cumulative asthenia resulted in DLT at 7.0 g m(-2). The median number of CD34+
      cells in 500 ml of whole blood after the first cycle (i.e. at start of cycle 2)
      was 1.15 x 10(6) kg(-1). This number was significantly greater after the second
      cycle (2.06 x 10(6) kg(-1), P = 0.01) and then gradually decreased after cycles
      three to six. After storing whole blood, the number of CD34+ cells had not
      decreased (median + 10%). We conclude that the method of combined bone marrow
      support by G-CSF and haematopoietic progenitor cells in autologous whole blood
      collected before each cycle of a 2-weekly regimen of cisplatin-ifosfamide does
      not result in clinically measurable reduced bone marrow toxicity compared with
      what can be expected by the use of G-CSF alone.

PMID- 9649160
TI  - Cisplatin-vindesine-mitomycin (MVP) vs cisplatin-ifosfamide-vinorelbine (PIN) vs
      carboplatin-vinorelbine (CaN) in patients with advanced non-small-cell lung
      cancer (NSCLC): a FONICAP randomized phase II study. Italian Lung Cancer Task
      Force (FONICAP).
AB  - In the present multicentre randomized phase II trial, the activity and toxicity
      of three platinum-based combination regimens for the treatment of advanced non
      small-cell lung cancer (NSCLC) were evaluated. The three regimens were: MVP
      (mitomycin-C 6 mg m(-2) on day 1, vindesine 3 mg m(-2) on days 1 and 15, and
      cisplatin 80 mg m(-2) on day 1 every 28 days), PIN (cisplatin 80 mg m(-2) day 1,
      ifosfamide 3 g m(-2) day 1 and vinorelbine 25 mg m(-2) day 1 and 8 every 21 days)
      and CaN (carboplatin 350 mg m(-2) day 1 and vinorelbine 25 mg m(-2) days 1 and 8
      every 28 days). A total of 140 chemotherapy-naive patients entered the study; 49
      patients were treated with MVP, 48 with PIN and 43 with CaN. Sixty-seven per cent
      of the patients had stage IV disease. Response rates, calculated on an 'intention
      to treat' basis, were as follows: MVP, 14.3% (95% CI 5.94-27.2%); PIN, 16.7% (95%
      CI 7.4-30.2%); and CaN, 14% (95% CI 5.3-27.9%). The overall median survivals were
      256, 269 and 243 days for patients treated with MVP, PIN and CaN respectively.
      Myelosuppression was the most frequent toxicity: grade 3-4 leucopenia was
      observed in 14.3%, 25% and 18.6% of patients treated with MVP, PIN and CaN
      respectively. This multicentre phase II randomized trial shows that MVP, PIN and
      CaN can be administered on an outpatient basis with acceptable toxicities.
      Unfortunately, the three regimens showed an activity significantly lower than
      that reported in previous single-institution phase II trials.

PMID- 9649161
TI  - The in vitro radiosensitivity of human head and neck cancers.
AB  - A study was made of the intrinsic radiosensitivity of 140 biopsy and surgical
      specimens of malignant head and neck tumours of different histologies. Using a
      soft-agar clonogenic assay, the material was assessed for the ability to grow in
      culture (colony-forming efficiency; CFE) and inherent tumour radiosensitivity
      (surviving fraction at 2 Gy, SF2). The success rate for obtaining growth was 74%
      (104/140) with a mean CFE of 0.093% (median 0.031) and a range of 0.002-1.3%. SF2
      was obtained for 88 of 140 specimens, representing a success rate of 63% with a
      mean SF2 of 0.48 (median 0.43) and a range of 0.10-1.00. There were no
      significant differences in radiosensitivity between different sites of the head
      and neck region. There were no significant relationships between SF2 and disease
      stage, nodal status, tumour grade, patient age, primary tumour growth pattern and
      CFE. The results were compared with those for other tumour types previously
      analysed with the same assay. The distribution of the SF2 values for the head and
      neck tumours was similar to that for 145 cervix carcinomas and there was no
      significant difference in mean radiosensitivity between the two tumour types.
      Also, there was no significant difference in radiosensitivity between head and
      neck tumours and either breast or colorectal cancers. However, a group of eight
      lymphomas was significantly more radiosensitive. These results confirm the
      feasibility of carrying out radiosensitivity measurements using a soft-agar
      clonogenic assay on head and neck tumours. In addition, the work has shown that
      radiosensitivity is independent of many clinical parameters and that the mean
      value is similar to that reported for cervix carcinomas.

PMID- 9649162
TI  - A multicentre phase II study of carboplatin and prolonged oral etoposide in the
      treatment of cancer of unknown primary site (CUPS).
AB  - Cisplatin-based combination chemotherapy is frequently used to treat patients
      with carcinoma of unknown primary site (CUPS). Response rates in the literature
      range from 12% to 26% and median survival from 5 to 7 months. The goal of this
      study was to evaluate the combination of carboplatin and prolonged oral etoposide
      in patients with CUPS, with the hope of minimizing toxicity but improving
      efficacy and convenience. Treatment consisted of carboplatin, 300 mg m(-2) on day
      1, and oral etoposide 50 mg on days 1-20, every 4 weeks for up to nine cycles. A
      total of 33 patients were treated and all were evaluable for toxicity. Non
      haematological toxicity was mild to moderate, with the exception of one case of
      grade 4 stomatitis. Grade 4 leucopenia was observed in eight (24%) patients and
      sepsis in four (12%), with two and possibly three treatment-related deaths. For
      the 26 patients evaluable for response, the response rate was 23% with responses
      lasting a median of 11 months (range 7-13 months), with one patient still
      responding at 12 months. An additional nine patients (35%) had stable disease.
      Median survival for all patients was 5.6 months (range 2 weeks to 33 months). The
      combination of carboplatin with prolonged oral etoposide has moderate activity
      similar to that of other platinum-based regimens and is a well tolerated,
      convenient, outpatient regimen. Dosing according to estimated creatinine
      clearance to achieve a carboplatin AUC of 6.0 mg ml(-1) min might have decreased
      the incidence of severe myelotoxicity without compromising the regimen's
      efficacy.

PMID- 9649163
TI  - Predictors of patients' mental adjustment to cancer: patient characteristics and
      social support.
AB  - Because being diagnosed with cancer is considered to be extremely stressful,
      cancer patients' mental adjustment has been widely studied. Previous studies have
      revealed that cancer patients' mental adjustment is correlated with the quality
      of life and the degree of psychological distress and have suggested that one of
      the most adaptive adjustments is 'fighting spirit' whereas one of the most
      maladaptive is 'helplessness/hopelessness'. However, little is known about the
      association between patients' mental adjustment to cancer and their spouses
      characteristics or social support network. This paper describes a study of cancer
      patients' characteristics and social support factors as predictors of the
      patients' responses to having cancer. A total of 455 ambulatory cancer patients
      completed the Mental Adjustment to Cancer (MAC) scale and participated in a
      structured interview about their characteristics and social support. The results
      of multiple regression analysis suggested that size of household, performance
      status, support from physicians and satisfaction with support were predictive of
      patients' fighting spirit, whereas age, education, size of household, performance
      status and satisfaction with support were predictive of
      helplessness/hopelessness.

PMID- 9649164
TI  - Prostate-specific antigen in the cerebrospinal fluid leads to diagnosis of
      solitary cauda equina metastasis: a unique case report and review of the
      literature.
AB  - A 79-year-old male patient presented with a subacute cauda syndrome caused by an
      intradural metastasis of the lumbosacral caudate fibres from an adenocarcinoma of
      the prostate, which had been treated 5 years earlier with external beam radiation
      therapy. Diagnosis could not be established by repeated magnetic resonance images
      (MRIs) during a 2-year period of increasingly severe radicular pain. Eventually,
      a small tumour mass could be visualized on the fourth MRI. Repeated normal serum
      prostate-specific antigen (PSA) did not hint at a prostate cancer metastasis
      (range 2.4-5.1 ng ml(-1)); however, PSA in the cerebrospinal fluid was found to
      be elevated (29.1 ng ml(-1)). Empirical radiation therapy of the caudate region
      did not improve radicular pain. Therefore, an exploratory surgical procedure was
      conducted, which confirmed the suspicion of an intradural prostate cancer
      metastasis. In conclusion, PSA in the cerebrospinal fluid provides a useful
      diagnostic tool for detecting intradural prostate cancer metastasis.

PMID- 9649165
TI  - The halcyon days of clinical field studies of dental caries prevention, 1960
      1980.

PMID- 9649166
TI  - Localization of estrogen-receptor-related antigen in human odontoblasts.
AB  - Estrogen receptors have been demonstrated in many osteogenic cell lines.
      Recently, we showed that estrogen deficiency induced by ovariectomy caused
      enhanced dentin formation in adult rats, suggesting that estrogen receptors may
      be present in dental tissues. Nothing is known about estrogen receptors in human
      teeth. We used immunohistochemical staining and immuno-blotting to demonstrate
      the presence of estrogen receptors in human pulp and/or the pulpo-dentinal
      border. Unerupted human wisdom teeth were surgically removed, frozen in liquid
      nitrogen, and prepared for immunological studies. Western blot analysis with
      monoclonal antibodies specific for human estrogen-receptor-related antigens
      demonstrated an approximately 29-kDa clear double band in the material scraped
      from the predentin-odontoblast border and in the fluid that emerged into the
      pulpal chamber, evidently from the odontoblasts. A weaker double band was also
      present in pulpal tissue samples. By immunohistochemical staining, estrogen
      receptor-related antigens were visualized in the predentinal-odontoblast region
      and in the pulpal blood vessels. Our results suggest the presence of estrogen
      receptors in human teeth, and thus the previously reported enhancement of the
      dentin formation in rats after ovariectomy may be mediated via these receptors.

PMID- 9649167
TI  - Quantitative analysis of amelogenin solubility.
AB  - Amelogenins are a group of extracellular enamel matrix proteins which are
      believed to be involved in the regulation of the size and habits of forming
      enamel crystals. The aim of this study was to compare the solubility properties
      of several amelogenins at various pH (from 4.0 to 9.0) at constant ionic strength
      (IS), and to examine the influence of buffer composition, IS, and divalent metal
      ions (including Ca2+, Mg2+, and Zn2+) on amelogenin solubility. The solubility of
      the recombinant murine amelogenin ("rM179") was minimum near its isoelectric
      point and increased rapidly below and above, regardless of buffer composition. A
      similar trend was observed for the native porcine ("25K") amelogenin. Porcine
      "23K" amelogenin was only sparingly soluble from pH of 4.0 to 9.0, in contrast to
      the analogous recombinant "rM166", which was more soluble in acidic solutions.
      The synthetic amelogenin polypeptide "TRAP" was extremely insoluble, while
      synthetic LRAP was readily soluble. Porcine "20K" amelogenin solubility increased
      strikingly as the solution pH was lowered from 7.0 to 6.0. Increasing IS
      decreased the solubility of rM179. While Zn2+ reduced rM179 solubility, Ca2+ and
      Mg2+ showed no significant effects. We conclude that the solubility of amelogenin
      was dependent on the primary structure, solution pH, and IS, and the low
      solubility of amelogenins under physiological conditions may result from their
      tendency to form quaternary (aggregate) structures in vivo.

PMID- 9649168
TI  - CO2 laser inhibitor of artificial caries-like lesion progression in dental
      enamel.
AB  - Several studies during the last 30 years have demonstrated the potential of laser
      pre-treatment of enamel or tooth roots to inhibit subsequent acid-induced
      dissolution or artificial caries-like challenge in the laboratory. The overall
      objective of ongoing studies in our laboratories is to determine, systematically,
      the optimum sets of parameters for carbon dioxide laser irradiation that will
      potentially effectively inhibit dental caries in enamel and tooth roots. The aim
      of the present study was to examine the roles of wavelength and fluence in the
      prevention of caries progression in vitro in enamel by means of a pH-cycling
      model. The hypothesis to be tested was that the highly absorbed 9.3- and 9.6
      microm wavelengths would be efficiently converted to heat, creating a temperature
      sufficiently high to reduce the acid-reactivity of the mineral and inhibit caries
      like lesion progression in dental enamel. One hundred and sixty caries-free tooth
      crowns were cleaned and varnished with acid-resistant varnish, leaving one
      exposed window of enamel. Twelve groups of 10 enamel samples were irradiated in
      their individual windows by one of the four wavelengths (9.3, 9.6, 10.3, or 10.6
      microm) of a tunable CO2 laser. Energy per pulse was 25, 50, 100, 200, or 250 mJ
      (25 pulses). Repetition rate was 10 Hz, and beam diameter was 1.6 mm. Fluence
      conditions of 1 to 12.5 J/cm2 per pulse were produced. All teeth, including 40
      non-irradiated controls, were subjected to pH-cycling to produce artificial
      caries-like lesions. Results were assessed by cross-sectional microhardness
      testing. Inhibition of caries progression of from 40% to 85% was achieved over
      the range of laser conditions tested. At 9.3 and 9.6 microm, 25 pulses at
      absorbed fluences of 1 to 3 J/cm2 produced inhibition on the order of 70% with
      minimal subsurface temperature elevation (< 1 degree C at 2 mm depth), comparable
      with inhibition produced in this model with daily fluoride dentifrice treatments.
      Safety and efficacy studies will be required in animals and humans before these
      promising laboratory results can be applied in clinical practice.

PMID- 9649169
TI  - Comparison between Er:YAG laser and conventional technique for root caries
      treatment in vitro.
AB  - Effective ablation of dental hard tissues by means of the erbium-doped:yttrium
      aluminum garnet (Er:YAG) laser has been reported recently, and its application to
      caries removal and cavity preparation has been expected. However, few studies
      have investigated the capability of the Er:YAG laser to treat caries. In the
      present study, the effectiveness of caries removal by using an Er:YAG laser in
      vitro was compared with that of conventional mechanical treatment. Thirty-one
      extracted human teeth with root caries were used. Half of the caries in each
      tooth was treated with the Er:YAG laser, and the other was removed with a
      conventional bur or was left untreated as a control. Laser treatment was
      performed by means of a combination of contact and non-contact irradiation modes
      with cooling water spray, with a new fiber delivery and contact probe system.
      Conventional bur treatment was conducted by means of a low-speed micromotor.
      Measurements of the time required for caries removal, histopathological
      observations of decalcified serial sections, scanning electron microscope (SEM)
      observations, and hardness measurements of the treated cavity-floor dentin were
      performed for each treatment. Due to the careful irradiation technique, a longer
      treatment time was required for the complete removal of carious dentin by the
      Er:YAG laser. However, the Er:YAG laser ablated carious dentin effectively with
      minimal thermal damage to the surrounding intact dentin, and removed infected and
      softened carious dentin to the same degree as the bur treatment. In addition, a
      lower degree of vibration was noted with the Er:YAG laser treatment. The SEM
      examination revealed characteristic micro-irregularities of the lased dentin
      surface. Our results show that the Er:YAG laser system is promising as a new
      technical modality for caries treatment.

PMID- 9649170
TI  - Activation of the immune system and systemic immune-complex deposits in Brown
      Norway rats with dental amalgam restorations.
AB  - Dental amalgam restorations are a significant source of mercury exposure in the
      human population, but their potential to cause systemic health effects is highly
      disputed. We examined effects on the immune system by giving genetically mercury
      susceptible Brown Norway (BN) rats and mercury-resistant Lewis (LE) rats silver
      amalgam restorations in 4 molars of the upper jaw, causing a body burden similar
      to that described in human amalgam-bearers (from 250 to 375 mg amalgam/kg body
      weight). BN rats with amalgam restorations, compared with control rats given
      composite resinous restorations, developed a rapid activation of the immune
      system, with a maximum 12-fold increase of the plasma IgE concentration after 3
      wks (p < 0.001; Mann-Whitney's test). LE rats receiving amalgam restorations
      showed no significant increase of plasma IgE (p > 0.05). After 12 wks, BN rats
      with amalgam restorations showed significantly increased (p < 0.05) titers of
      immune-complex (IC) deposits in the renal glomeruli and in the vessel walls of
      internal organs. These rats also showed a significant (p < 0.05), from six- to
      130-fold, increase in tissue mercury concentration in the concentration order
      kidney > spleen > cerebrum occipital lobe > cerebellum > liver > thymus, and the
      tissue silver concentration was significantly (p < 0.05) increased from three- to
      11-fold. Amalgam-implanted BN rats showed a significant (p < 0.05) increase in
      copper concentration in the kidney and spleen, and in kidney selenium
      concentration. We conclude that dental amalgam restorations release substantial
      amounts of their elements, which accumulate in the organs and which, in
      genetically susceptible rats, give rise to activation of the immune system and
      systemic IC deposits.

PMID- 9649171
TI  - The process of physical weakening and dissolution of the HA-coated implant in
      bone and soft tissue.
AB  - Hydroxyapatite (HA)-coated implants were developed to promote osseointegration of
      titanium implants and to overcome the mechanical drawbacks of solid HA implants.
      Although many clinical reports on the prognosis of HA-coated implants have
      reported high success rates, the risks of dissolution and weakening of the
      coating have been noted. We hypothesized that the chemical and mechanical
      stability of HA coating are affected by its microstructural characteristics. The
      present study investigates differences in the microstructures of available HA
      coated implants, before and after implantation into the coxal bones of dogs for
      periods ranging from 3 weeks to 10 months and under the coxal periosteum of dogs
      for 10 months. The results of transmission electron microscopy and energy
      dispersive x-ray analysis revealed that crystallization of super-fine HA crystals
      occurred in the amorphous phase of the HA coating and progressed over time. This
      crystallization weakens HA-coated implants by making the amorphous phase brittle,
      causing stress accumulation within the coating, and causing a decrease in the
      binding strength between the coating and the substrate. Furthermore, the HA
      coating dissolved in soft tissue. Dissolution started with the super-fine HA
      crystals in the crystallized portion that was originally part of the amorphous
      phase.

PMID- 9649172
TI  - Do dental composites always shrink toward the light?
AB  - Many of the current light-curing composite restorative techniques are
      rationalized in compliance with the theory that composite shrinks toward the
      light. Shrinkage directed toward the margins is believed to be responsible for
      the observed improved marginal properties. However, the dental literature does
      not consistently support this theory. Experimental determination of contraction
      patterns is very difficult. In this study, a finite element technique is used to
      analyze the direction of composite shrinkage as it cures. The process of
      polymerization can be characterized by pre- and post-gel phases. The stress
      developed in a restoration can be relieved quickly by the flow of material still
      in the pre-gel phase. Residual stresses arise after gelation. Both auto- as well
      as photo-curing composites were analyzed. In photo-curing composites, the gel
      point varies throughout the material with the intensity of the light.
      Experimentally determined light transmittance data for different materials were
      used in the simulation. Degree of cure and time-dependent shrinkage properties
      were also included from experimental measurements. The analysis showed that the
      shrinkage direction was not significantly affected by the orientation of the
      incoming curing light, but instead was mostly determined by the bonding of the
      restoration to the tooth and by the free surfaces. Consequently, differences
      between the contraction patterns of auto- and photo-cure were minimal. It was
      concluded that composite does not shrink toward the light, but that the direction
      is predominantly determined by cavity shape and bond quality. Improved marginal
      properties should be pursued by the optimization of other factors, such as the
      polymerization process, the curing procedure, and the bond quality. The direction
      of shrinkage vectors in response to light position does not seem to be an
      appropriate criterion for the optimization of marginal quality.

PMID- 9649173
TI  - Distortion behavior of heat-activated acrylic denture-base resin in conventional
      and long, low-temperature processing methods.
AB  - There have been many reports on fatal distortion of heat-activated acrylic
      denture-base resin which is still widely used in the field of removable
      prosthodontics. However, these reports have failed to report quantitatively on
      polymerization and thermal shrinkage factors. In the present study, we attempted
      to verify that the shrinkage of heat-activated acrylic denture-base resin was
      caused mainly by thermal contraction after processing. Furthermore, we examined
      the degree of distortion resulting from long, low-temperature processing, and
      compared the results with that of the conventional method. The strain gauge and
      thermo-couple were embedded in a specimen at the time of resin packing. The
      measurement started from the beginning of processing and continued until the
      specimen was bench-cooled and immediately before and after it was de-flasked, as
      well as during seven-day immersion in water at 37 degrees C. The resin expanded
      when processed by the conventional method. Meanwhile, mild shrinkage, possibly
      polymerization shrinkage, was observed when the resin was processed by the low
      temperature method. This suggested that polymerization shrinkage was compensated
      for by thermal expansion during processing by the conventional method. Moreover,
      the shrinkage strains in the period from the completion of processing to
      immediately after de-flasking, in both the conventional and low-temperature
      methods, were identical to the theoretical value of thermal shrinkage which we
      obtained by multiplying the linear coefficients of thermal expansion by
      temperature differences. The shrinkage strain in the specimen processed by the
      low-temperature method, measured from the end of processing to immediately after
      de-flasking, averaged 64% of that in the specimen processed by the conventional
      method. The results revealed quantitatively that the shrinkage of heat-activated
      acrylic denture-base resin was mainly thermal shrinkage, and demonstrated the
      advantage of the low-temperature method in reducing thermal shrinkage.

PMID- 9649174
TI  - Effects of dopaminergic drugs, occlusal disharmonies, and chronic stress on non
      functional masticatory activity in the rat, assessed by incisal attrition.
AB  - Observational methods and the recording of nonspecific jaw movements or
      masticatory muscle activity have been used to evaluate oral parafunctional
      movements in animal models of bruxism. In this study, we have used a new approach
      in which the non-functional masticatory activity in the rat was assessed by the
      measurement of incisal attrition, with the aim of investigating the role of
      diverse factors involved in the etiology of bruxism. We quantified the attrition
      rate weekly by making superficial notches in the lower incisors and measuring the
      distances to the incisor edges. Repeated stimulation of the dopaminergic system
      with apomorphine led to an enhancement of the non-functional masticatory activity
      (p < 0.0001). The severity of the apomorphine-induced oral behavior was
      positively correlated (r(s) = 0.69, p < 0.01) with an increase in the incisal
      attrition rate (20.9%, p < 0.0001). Apomorphine-induced non-functional
      masticatory activity was strongly enhanced by the placement of an acrylic cap on
      both lower incisors (306%, p < 0.0001), but not by the cutting of a lower
      incisor. Repeated cocaine administration also increased the attrition rate
      (22.5%, p < 0.0001). However, neither chronic blockade of dopaminergic receptors
      with haloperidol, nor its withdrawal, modified attrition. In addition, since
      emotional disturbances are considered to be causal factors of bruxism, we tested
      whether experimental stress might accelerate tooth wear. Exposure to two
      different chronic stress regimes did not induce significant changes in incisal
      attrition. Moreover, exposure to chronic stress after the withdrawal of chronic
      haloperidol treatment did not alter attrition either. These results partially
      support the role of the central dopaminergic system in bruxism and suggest that
      stress, in general, may not be a relevant factor in tooth wear.

PMID- 9649175
TI  - Pain maps from facial pain patients indicate a broad pain geography.
AB  - Two hundred consecutive female patients, who were referred to a university-based
      facial pain clinic, were asked to mark all painful sites on sketches showing the
      contours of a human body in the frontal and rear views. The drawings were
      analyzed with transparent templates containing 1875 (frontal view) and 1929 (rear
      view) square cells of equal size. The average patient scored 71.8 cells in the
      frontal and 99.7 cells in the rear view (corresponding to 3.8% and 5.2% of the
      maximum possible scores). In individual patient drawings, however, up to 42.7%
      and 44.9% of all cells were marked. Only 37 cases (18.5%) exhibited pain that was
      limited to the trigeminal system. An analysis of the pain distribution according
      to the arrangements of dermatomes revealed three distinct clusters of patients:
      (1) pain restricted to the region innervated by the trigeminal nerves (n = 37);
      (2) pain in the trigeminal dermatomes and any combination involving the spinal
      dermatomes C2, C3, and C4, but no other dermatomes (n = 32); and (3) pain sites
      involving dermatomes in addition to the ones listed above (n = 131). Mean ages in
      the three clusters were 38.7, 35.5, and 37.5 years, respectively (p = 0.62,
      n.s.). Widespread pain existed for longer durations (median, 48 months) than
      conditions involving local and regional pain (median, 24 months) (p = 0.02, s.).
      Our findings showed that among a great percentage of persistent facial pain
      patients the pain distribution is more widespread than commonly assumed, and that
      the persistence of pain in the regional and widespread pain presentations is
      significantly greater than in cases with pain limited to the trigeminal system.

PMID- 9649176
TI  - Prostatein (or rat prostatic steroid binding protein) is a major autoantigen in
      experimental autoimmune prostatitis.
AB  - Experimental autoimmune prostatitis (EAP) is a disease that could be considered
      an experimental model of human non-bacterial prostatitis. In this experimental
      model, male rats are intradermally immunized with a saline extract of male sex
      accessory glands (RAG) in an adequate adjuvant. The prostatitis observed in the
      immunized animals develops as a consequence of the immune response against RAG
      antigens, and the histological lesion is strikingly similar to the pattern of
      prostatic inflammation observed in the human disease. In this study, we purified
      one of the prostatic autoantigens recognized by the autoantibodies in our model.
      Amino acid sequence analysis identified the purified protein as prostatein or rat
      prostatic steroid binding protein, a member of the uteroglobin superfamily.
      Prostatein was recognized not only by the humoral autoimmune response, but also
      by the cellular autoimmune response. Certainly, the DTH response and lymph node
      cell proliferative assays against prostatein in immunized animals yielded
      positive results. Prostatein is not only the target of the autoimmune response in
      animals immunized with the whole extract, but also an inducing antigen of the
      disease. Purified prostatein, when incorporated to an adequate adjuvant, elicited
      cellular and humoral autoimmune response and lesion in the prostate gland. The
      identification of one of the target antigens in autoimmune prostatitis has
      provided a further refinement and characterization of our model, which could
      serve for a better understanding of the aetiology, pathogenesis and
      pathophysiology of non-bacterial prostatitis.

PMID- 9649177
TI  - Elevated serum levels of soluble Fas/APO-1 (CD95) in patients with hepatocellular
      carcinoma.
AB  - Fas (APO-1/CD95)-mediated apoptosis plays an important role in liver cell
      destruction in viral hepatitis. Using sandwich ELISA, we measured serum levels of
      soluble Fas (sFas) in patients with hepatocellular carcinoma (HCC) who were
      positive for hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus (HCV)
      antibody. sFas levels were significantly higher in HCC patients (median 4.07
      ng/ml; range 0.14-29.18 ng/ml) than levels in age-matched healthy donors (0.29
      ng/ml; 0-4.90 ng/ ml) (P < 0.0001) and HBsAg or anti-HCV antibody-positive
      patients with liver cirrhosis (LC) (2.16 ng/ ml; 0.24-8.39 ng/ml) (P = 0.0015).
      An arbitrary cut-off level of 3.03 ng/ml (mean + 3 s.d. of controls) revealed the
      positive frequency of sFas in each group: 1.7% in healthy subjects, 25.9% in LC,
      and 59.0% in HCC (sensitivity 59.0% and specificity 74.1%). All HCC sera tested
      contained transmembrane-deleted sFas and some contained another sFas lacking the
      Fas C-terminal. The positive frequency of either sFas (59.0%) or alpha
      fetoprotein (AFP) (57.4%) in HCC patients reached 77.0%. HCC patients with
      multiple tumour foci (7.53 ng/ml; 1.40-29.18 ng/ml) had significantly higher sFas
      levels than did patients with a solitary tumour (2.70 ng/ml; 0.14-19.0 ng/ml) (P
      = 0.003). In all of the sFas-positive patients with a solitary tumour, surgical
      removal of the tumour reduced sFas levels to the negative in the first post-op
      week. These findings suggest that sFas may be closely linked with HCC and may be
      a candidate for a clinical parameter for HCC.

PMID- 9649178
TI  - Differential expression of cytokine transcripts in human epithelial ovarian
      carcinoma by solid tumour specimens, peritoneal exudate cells containing tumour,
      tumour-infiltrating lymphocyte (TIL)-derived T cell lines and established tumour
      cell lines.
AB  - T cell lines derived in low concentrations of recombinant IL-2 (rIL-2) from TIL
      of patients with epithelial ovarian carcinoma (EOC) often exhibit specific
      cytotoxicity against autologous tumour cells. However, the ability of T cells at
      the tumour site to respond to ovarian carcinoma cells may be affected by the
      production of cytokines by the various cell types present. Using reverse
      transcriptase-polymerase chain reaction (RT-PCR) we investigated cytokine
      transcripts in: (i) established EOC tumour cell lines; (ii) solid tumour
      specimens or peritoneal exudate cells (PEC) from ascites or peritoneal washings
      of patients with EOC; and (iii) CD4+ TCRalphabeta+ and CD8+ TCRalphabeta+ TIL
      derived T cell lines developed in rIL-2. We have found that (i) established EOC
      tumour cell lines expressed transcripts for transforming growth factor-beta 2
      (TGF-beta2) (7/7), but not IL-10 (0/7) or interferon-gamma (IFN-gamma) (0/7) and
      rarely IL-2 (1/7); (ii) PEC expressed transcripts for IL-2 (12/13), IL-10 (9/13),
      and TGF-beta2 (12/13), and less often, IFN-gamma (3/13), whereas solid tumour
      specimens from eight patients with EOC expressed transcripts for IL-2 (4/8), TGF
      beta2 (4/8), and IL-10 (5/8), but not for IFN-gamma (0/8); (iii) CD4+
      TCRalphabeta+ T cell lines expressed transcripts for IFN-gamma (4/4), IL-2 (4/4)
      and IL-10 (3/4), whereas CD8+ TCRalphabeta+ T cell lines expressed transcripts
      for IFN-gamma (5/5), IL-2 (1/5) and IL-10 (2/5). None of these T cell lines
      expressed TGF-beta2 transcripts. The frequency of IL-2 and TGF-beta2 transcripts
      in solid tumours was significantly lower than in the PEC (P = 0.0475). CD4+ or
      CD8+ T cell lines expressing IFN-gamma, IL-2 and IL-10 transcripts were derived
      in culture with rIL-2 from the TIL of specimens that did not necessarily express
      these cytokines in the absence of rIL-2. The frequency of cytokine transcripts in
      T cell lines compared with these same transcripts in the PEC was significantly
      higher for IFN-gamma (P = 0.0005) and lower for TGF-beta2 (P = 0.0001). An
      association was observed between the expression of cytokine transcripts in vivo
      or by TIL-derived cell lines and functions exhibited by either production of
      cytokines or in vitro cytotoxicity.

PMID- 9649179
TI  - 1,25-Dihydroxyvitamin D3 restores sensitivity to cyclophosphamide-induced
      apoptosis in non-obese diabetic (NOD) mice and protects against diabetes.
AB  - The activated form of vitamin D, 1,25(OH)2D3, and its analogues can prevent type
      I diabetes in NOD mice. Protection is achieved without signs of systemic
      immunosuppression and is associated with a restoration of the defective immune
      regulator system of the NOD mice. The aim of the present study was to investigate
      whether this restoration of regulator cell function is the only mechanism in the
      prevention of diabetes by 1,25(OH)2D3. We tested therefore if 1,25(OH)2D3 could
      prevent cyclophosphamide-induced diabetes, since diabetes occurring after
      cyclophosphamide injection is believed to be due to an elimination of suppresser
      cells. NOD mice treated with 1,25(OH)2D3 (5 microg/kg every 2 days) from the time
      of weaning were clearly protected against diabetes induced by cyclophosphamide
      (200 mg/kg body wt at 70 days old) (2/12 (17%) versus 36/53 (68%) in control
      mice, P < 0.005). By co-transfer experiments it was demonstrated that
      cyclophosphamide had indeed eliminated the suppresser cells present in
      1,25(OH)2D3-treated mice. Since cyclophosphamide injection did not break the
      protection offered by 1,25(OH)2D3, it was clear that diabetogenic effector cells
      were affected by 1,25(OH)2D3 treatment as well. This was confirmed by the finding
      that splenocytes from 1,25(OH)2D3-treated mice were less capable of transferring
      diabetes in young, irradiated NOD mice, and by the demonstration of lower Th1
      cytokine levels in the pancreases of 1,25(OH)2D3-treated, cyclophosphamide
      injected mice. This better elimination of effector cells in 1,25(OH)2D3-treated
      mice could be explained by a restoration of the sensitivity to cyclophosphamide
      induced apoptosis in both thymocytes and splenocytes, in normally apoptosis
      resistant NOD mice. Altogether, these data indicate that the protection against
      diabetes offered by 1,25(OH)2D3 may be independent of the presence of suppresser
      cells, and may involve increased apoptosis of Th1 autoimmune effector cells.

PMID- 9649180
TI  - Analysis of graft-versus-host disease (GVHD) and graft rejection using MHC class
      I-deficient mice.
AB  - GVHD is a major complication in allogeneic bone marrow transplantation (BMT). MHC
      class I mismatching increases GVHD, but in MHC-matched BMT minor
      histocompatibility antigens (mH) presented by MHC class I result in significant
      GVHD. To examine the modification of GVHD in the absence of cell surface MHC
      class I molecules, beta2-microglobulin-deficient mice (beta2m(-/-)) were used as
      allogeneic BMT recipients in MHC- and mH-mismatched transplants. Beta2m(-/-) mice
      accepted MHC class I-expressing BM grafts and developed significant GVHD. MHC (H
      2)-mismatched recipients developed acute lethal GVHD. In contrast, animals
      transplanted across mH barriers developed indolent chronic disease that was
      eventually fatal. Engrafted splenic T cells in all beta2m(-/-) recipients were
      predominantly CD3+alphabetaTCR+CD4+ cells (15-20% of all splenocytes). In
      contrast, CD8+ cells engrafted in very small numbers (1-5%) irrespective of the
      degree of MHC mismatching. T cells proliferated against recipient strain antigens
      and recognized recipient strain targets in cytolytic assays. Cytolysis was
      blocked by anti-MHC class II but not anti-CD8 or anti-MHC class I monoclonal
      antibodies (MoAbs). Cytolytic CD4+ T cells induced and maintained GVHD in mH
      mismatched beta2m(-/-) mice, supporting endogenous mH presentation solely by MHC
      class II. Conversely, haematopoietic beta2m(-/-) cells were unable to engraft in
      normal MHC-matched recipients, presumably due to natural killer (NK)-mediated
      rejection of class I-negative cells. Donor-derived lymphokine-activated killer
      cells (LAK) were unable to overcome graft rejection (GR) and support engraftment.

PMID- 9649181
TI  - Phenotypic and functional modulation of T cells in vivo by extrathymic T cells
      when T cells with MHC class II disparity were injected into athymic nude mice.
AB  - TCRhigh cells are generated by the mainstream of T cell differentiation in the
      thymus, whereas TCRint cells (or NK1.1+ T cells) are generated extrathymically in
      the liver and by an alternative intrathymic pathway. It is still unknown how
      these T cell populations interact in vivo with each other. To investigate the
      interaction of TCRint cells with TCRhigh cells, we used congenitally athymic nude
      (B6-nu/nu) mice which carry only TCRint cells in all immune organs. When TCRhigh
      cells from B6-C-H-2bm12 (bm12) mice (i.e. I-Abm12) were injected into B6-nu/nu
      mice (i.e. 1-Ab), the expanding T cell population was a mixture of TCRhigh cells
      of donor origin and TCRint cells of recipient origin. However, 9 Gy-irradiated
      nude mice permitted a full expansion of TCRhigh cells which expressed the IL
      2Ralpha+beta+ phenotype, namely, they were at the most activated state. These
      mice died of acute graft-versus-host disease (GVHD) within 5 days. On the other
      hand, non-irradiated nude mice suppressed the expansion of TCRhigh cells of donor
      origin and such TCRhigh cells continued to have the IL-2Ralpha(+/-)beta+
      phenotype. These mice could survive but showed signs of chronic GVHD thereafter.
      In both situations, CD4+alphabeta T cells expanded irrespective of donor or
      recipient origin. These results suggest that TCRint cells in the recipient mice
      possess a regulatory function in relation to donor TCRhigh cells; as a result,
      fully activated TCRhigh cells acquired the IL-2Ralpha+beta+ phenotype and injured
      the host, but TCRhigh cells suppressed in vivo remained as the IL-2Ralpha(+/
      )beta+ phenotype and only partially injured the host.

PMID- 9649182
TI  - Isolation and phenotypic characterization of colonic macrophages.
AB  - Macrophages play an important role in the intestinal mucosal immune system.
      However, they are a poorly defined cell population. We therefore determined their
      phenotype in normal colonic mucosa. Macrophages were isolated from colonic
      biopsies and surgical specimens by collagenase digestion. Colonic macrophages
      were positively sorted by anti-CD33 magnetic beads. Flow cytometric triple
      fluorescence analysis was applied to study CD14, CD16, CD33, CD44, CD11b, CD11c,
      CD64, HLA-DR, CD80, CD86 and CD3/CD19 expression. CD33 was evaluated as a
      positive marker for intestinal macrophages. CD33+ cells isolated from normal
      colonic mucosa showed co-expression of the established intracellular macrophage
      marker CD68 in FACS analysis. CD33+ cells were capable of phagocytosis. Isolation
      of this cell population by magnetic anti-CD33 beads and culture resulted in a 4.2
      40-fold increase in IL-1beta and 4.5-44-fold increase in tumour necrosis factor
      alpha (TNF-alpha) secretion compared with unsorted lamina propria mononuclear
      cells (LPMC). Of the CD33+ cells, 90.9 +/- 6.9% (mean +/- s.d.) were CD44+.
      However, macrophages from colonic mucosa showed only a low expression of CD14
      (10.5 +/- 3.8%), CD16 (10.1 +/- 3.9%), HLA-DR (27.3 +/- 9.2%), CD11b (17.4 +/-
      6.8%), CD11c (17.8 +/- 10.4%). Furthermore, expression of CD80 (9.2 +/- 4.2%) and
      CD86 (15.1 +/- 7.3%) was low, suggesting a low ability of normal intestinal
      macrophages to activate T cells and T cell-mediated immune responses. We conclude
      that CD33 is useful for the isolation and flow cytometric characterization of
      colonic macrophages. These cells exhibit a single phenotype in normal mucosa
      (CD33++, CD44++, CD14-, CD16-, CD11b-, CD11c-, HLA-DRlow, CD80-, CD86-) lacking
      lipopolysaccharide (LPS) receptor and costimulatory molecules.

PMID- 9649183
TI  - CD4+ T cells from 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis
      rodents migrate to the recipient's colon upon transfer; down-regulation by CD8+ T
      cells.
AB  - CD4+ T cells play an important role in the aetiology of inflammatory bowel
      disease (IBD), but it is not clear which factor(s) cause activation of these
      cells. The aim of this study was to examine the effects of adoptive transfer of
      splenic (CD4+) T cells from TNBS/ethanol-sensitized donor rats to naive
      recipients and the migration pattern of transferred T cells. For the transfer
      experiments, colitis was induced in rats by colonic administration of
      TNBS/ethanol. Seventeen days later, either total splenic T cells or CD4+, or CD8+
      T cells were transferred to naive recipients. At days 1, 2 and 3 after transfer,
      the recipients were killed and the migration pattern of the transferred T cells
      was studied, as well as inflammatory cells in several organs, including the
      colon. To determine cytokine profiles of the T cells, colitis was induced in
      mice. Therefore, different combinations of 2,4-dinitrobenzene sulfonic acid
      (DNBS) in ethanol or saline, or ethanol alone were intrarectally administered. At
      day 9 after induction of colitis, mice were killed and cytokine profiles in the
      colon were studied by reverse transcriptase-polymerase chain reaction (RT-PCR)
      and immunohistochemistry. The results show that CD4+ T cells from donor rats with
      TNBS/ethanol-induced colitis migrate in particular to the colon upon transfer to
      naive recipients, and that this process is down-regulated by CD8+ T cells. This
      migration is probably caused by T cell recognition of the colonic bacterial flora
      and initiates an inflammatory reaction in the recipient's colon, characterized by
      an increase of the recipient's own T cells, macrophages, and neutrophils. In the
      mice experiments we showed that a second administration of DNBS/ethanol or
      ethanol alone, which presumably causes bacterial translocation, results in
      increased numbers of T cells into the colon, accompanied by an increase in Th1
      cytokines. These data suggest that Th1 cells recognize the colonic bacterial
      flora.

PMID- 9649184
TI  - Interactions between peripheral blood CD8 T lymphocytes and intestinal epithelial
      cells (iEC).
AB  - Intestinal intraepithelial lymphocytes (iIEL) are primarily CD8 cells and most of
      them have a CD28- phenotype, the phenotype of effector cytotoxic T cells. We
      asked whether the predominance of CD8+CD28- T cells in the gut may result from
      peripheral blood T cells preferentially migrating to the iIEL compartment and
      adhering to iEC. Compared with CD4 cells, adhesion of resting CD8+ T cells to iEC
      cell lines was significantly higher. Adhesion could be blocked with a MoAb to
      gp180, a molecule expressed on iEC which is known to interact with CD8/lck. No
      significant difference in the level of adhesion was observed between CD8+CD28+
      and CD8+CD28- T cells. Thus CD8 cells may preferentially migrate to the iIEL
      compartment, but loss of CD28 expression could occur in situ after migration.
      Consistent with this hypothesis, the CD8+CD28- cells became enriched after co
      culturing T cells with iEC cell lines and primary iEC. Induction of the CD8+CD28-
      phenotype in cord blood and adult T cells was observed in co-cultures with iEC
      and also with mitogens and superantigens. In the latter case, CD28 down
      modulation was seen specifically in the Vbeta subset targeted by the
      superantigen, indicating that loss of CD28 expression is a direct result of T
      cell receptor (TCR)-mediated stimulation. The combined results suggest that
      CD8+CD28- T cells are antigen experienced T cells, and that they may have a
      survival advantage in the presence of gut epithelial cells in vitro. This may
      contribute to the predominance of CD8+CD28- T cells in the iIEL compartment.

PMID- 9649185
TI  - Decay-accelerating factor (DAF) in stool specimens as a marker of disease
      activity in patients with ulcerative colitis (UC).
AB  - Colonic epithelial cells of patients with UC express DAF in relation to the
      severity of mucosal inflammation. The aim of this study was to determine whether
      this factor in stool could be used as a marker of disease activity in UC
      patients. Stool DAF was measured by use of an immunoassay in 181 stool specimens
      obtained from 55 patients with UC of various levels of disease activity. Stool
      DAF concentrations in patients whose UC was active (0.0-785.6 ng/g stool; median
      47.1 ng/g; n = 115) were significantly higher than concentrations in patients
      whose disease was inactive (0.0-48.6 ng/g; median 0.0 ng/g; n = 66) (P < 0.0001).
      Values in active UC patients also were higher than those in control patients with
      diarrhoea (0.0-30.0 ng/g; median 0.0 ng/g; n = 26) (P < 0.0001) and in control
      subjects without apparent colorectal disease (0-20.4 ng/g; median 0.0 ng/g; n =
      44) (P < 0.0001). The elevated levels of stool DAF obtained from UC patients in
      relapse declined markedly in specimens collected after the disease went into
      remission following medical therapy. Stool DAF levels correlated with the
      severity of endoscopic and histological findings and the degree of DAF expression
      on the colonic epithelia. Our results suggest that the measurement of stool DAF
      is useful as a non-invasive means of monitoring intestinal disease activity in
      patients with UC.

PMID- 9649186
TI  - Oxidative stress suppresses transcription factor activities in stimulated
      lymphocytes.
AB  - Effects of oxidative stress on stimulation-dependent signal transduction, leading
      to IL-2 expression, were studied. Purified quiescent human blood T lymphocytes
      were subjected to: (i) acute exposure to hydrogen peroxide; (ii) chronic exposure
      to hydrogen peroxide; and (iii) acute exposure to ionizing radiation. The cells
      were then stimulated for 6 h. DNA-binding activities (determined by the
      electrophoretic mobility shift assay) of three transcription factors: NFkappaB,
      AP-1 and NFAT, were abolished in the lymphocytes by all three modes of oxidative
      stress. The lymphocytes exhibited lipid peroxidation only upon exposure to the
      lowest level of hydrogen peroxide used (20 microM). All three modes of oxidative
      stress induced catalase activity in the lymphocytes. The only exception was
      hydrogen peroxide at 20 microM, which did not induce catalase activity. We
      conclude that: (i) suppression of specific transcription factor functions can
      potentially serve as a marker of exposure to oxidative stress and its effects on
      human lymphocytes; (ii) lipid peroxidation is only detectable in human
      lymphocytes upon exposure to weak oxidative stress which does not induce catalase
      activity; (iii) therefore, transcription factor DNA-binding activities are more
      sensitive to oxidative stress than lipid peroxidation.

PMID- 9649187
TI  - Somatic hypermutation of immunoglobulin genes is independent of the Bloom's
      syndrome DNA helicase.
AB  - Immunoglobulin gene somatic mutation leads to antibody affinity maturation
      through the introduction of multiple point mutations in the antigen binding site.
      No genes have as yet been identified that participate in this process. Bloom's
      syndrome (BS) is a chromosomal breakage disorder with a mutator phenotype. Most
      affected individuals exhibit an immunodeficiency of undetermined aetiology. The
      gene for this disorder, BLM, has recently been identified as a DNA helicase. If
      this gene were to play a role in immunoglobulin mutation, then people with BS may
      lack normally mutated antibodies. Since germ-line, non-mutated immunoglobulin
      genes generally produce low affinity antibodies, impaired helicase activity might
      be manifested as the immunodeficiency found in BS. Therefore, we asked whether
      BLM is specifically involved in immunoglobulin hypermutation. Sequences of
      immunoglobulin variable (V) regions were analysed from small unsorted blood
      samples obtained from BS individuals and compared with germ-line sequences. BS V
      regions displayed the normal distribution of mutations, indicating that the
      defect in BS is not related to the mechanism of somatic mutation. These data
      strongly argue against BLM being involved in this process. The genetic approach
      to identifying the genes involved in immunoglobulin mutation will require further
      studies of DNA repair- and immunodeficient individuals.

PMID- 9649188
TI  - Genetic identification of antigens exposed in damaged endothelial cells as
      laminin-binding proteins.
AB  - A monoclonal antibody, D5G2, which reacts in a balloon angioplasty damage model
      with unfixed damaged but not with unfixed undamaged human endothelial cells, was
      used to screen a human endothelial cDNA library in an Escherichia coli/lambda
      gt11 expression system. Sequences of DNA inserts in D5G2+ phage clones matched
      those reported for a laminin-binding protein, LBP-32. Both D5G2 and purified
      laminin bound to a polypeptide of 55 kD on PVDF membranes carrying
      electrophoretically separated endothelial cell lysates, D5G2 also bound to
      recombinant LBP expressed in E. coli, and showed similar staining patterns on
      human and bovine endothelial cells to another characterized anti-LBP antibody.
      Increased staining of unfixed endothelial cells on detergent permeabilization
      suggests that D5G2 binds to intracellular laminin-binding protein made accessible
      by cell membrane injury. Antibodies to intracellular targets exposed by cell
      damage may be useful in anchoring therapeutic agents at sites of vascular damage.

PMID- 9649189
TI  - Sulphatide-binding properties are shared by serum amyloid P component and a
      polyreactive germ-line IgM autoantibody, the TH3 idiotype.
AB  - Serum amyloid P component (SAP) concentration was elevated in sera from leprosy
      patients, significantly so above endemic controls in lepromatous cases. In the
      sera of lepromatous leprosy (LL) patients who experienced an erythema nodosum
      leprosum (ENL) episode the SAP fell at the onset of ENL and remained low
      throughout, in two of three cases. Changes in SAP concentration parallel anti
      sulphatide IgM concentrations. TH3, a monoclonal IgM germ-line antibody derived
      from a LL patient, and SAP share similar binding patterns. In this study we
      demonstrate binding to heparin and sulphatide. Moreover, SAP inhibited the
      binding of TH3 to sulphatide, as well as anti-sulphatide IgM found in a range of
      sera, and anti-sulphatide IgG in the only sera sample in which it was found. The
      observation that anti-TH3 idiotype monoclonal and polyclonal anti-SAP antibodies
      both inhibited the binding of TH3 and IgM in sera (but not IgG) to sulphatide
      without binding to sulphatide themselves further demonstrated similar binding
      specificities. The observations of similarity in binding reinforce ideas that SAP
      may function as a primitive opsonin, but the clear ability to inhibit binding of
      autoantibodies suggests that SAP may play a role in ameliorating tissue and
      particularly nerve damage in leprosy patients.

PMID- 9649190
TI  - Chemokines produced by mesothelial cells: huGRO-alpha, IP-10, MCP-1 and RANTES.
AB  - Recently we showed the in vivo relevance of chemokines in cases of bacterial
      peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients.
      Mesothelial cells, the most numerous cells in the peritoneal cavity, are
      hypothesized to function as a main source of chemokine production. We
      investigated the time- and dose-dependent expression patterns of four chemokines
      by mesothelial cells at the mRNA and protein level in response to stimulation
      with physiological doses of proinflammatory mediators that are present at the
      site of bacterial inflammation. Besides the chemokines huGRO-alpha (attractant
      for neutrophils), MCP-1 and RANTES (monocyte attractants), the expression and
      production of IP-10 was analysed. Mesothelial cells were cultured and stimulated
      with either IL-1beta, tumour necrosis factor-alpha (TNF-alpha) or IFN-gamma or
      combinations of these. The time- and dose-dependent mRNA expression of the
      chemokines was determined by Northern blot analysis and the protein production by
      ELISA. It was concluded that mesothelial cells could indeed be triggered by the
      mentioned stimuli to induce mRNA and protein production (huGRO-alpha and IP-10)
      or to augment constitutive protein production (MCP-1). However, RANTES mRNA and
      protein production could only be induced in some cases and only in small amounts.
      The chemokine response of mesothelial cells was regulated differentially,
      depending on the stimulus and the chemokine measured. In distinct cases,
      combination of the stimuli led to synergy in mRNA expression and protein
      production. The presented in vitro data support our hypothesis that mesothelial
      cells in vivo are the main source of relevant chemokines in response to
      proinflammatory mediators, suggesting an important role for mesothelial cells in
      host defence.

PMID- 9649191
TI  - Distinct modulation by interferon-gamma (IFN-gamma) of CD23 expression on B and T
      lymphocytes of atopic subjects.
AB  - The low-affinity IgE receptor (FcepsilonRII/CD23) plays a role in IgE production.
      Cytokines participating in IgE synthesis also modulate CD23 expression on
      lymphocytes, but whether this modulation is different in atopic subjects remains
      unclear. We studied CD23 expression on B and T lymphocytes in 10 asthmatic
      patients with Dermatophagoides pteronyssinus hypersensitivity and 10 healthy non
      atopic subjects. Studies were performed by flow cytometry, in phytohaemagglutinin
      (PHA) or IL-4-stimulated mononuclear cell cultures, alone or in the presence of
      IFN-gamma. Soluble CD23 (sCD23) released in the culture supernatants was measured
      by enzyme-linked immunoassay. Both PHA and IL-4 induced the expression of CD23 on
      lymphocytes of atopic and non-atopic subjects. Whereas PHA increased both the
      percentage and mean fluorescence intensity of CD23+ B and T cells, IL-4 alone did
      not increase the percentage of CD23+ T cells. The effects of IFN-gamma were
      different in both groups, since it was able to reduce the percentage of PHA
      stimulated CD23+ T cells only in non-atopic individuals. In non-atopic subjects
      more than atopic, levels of sCD23 were increased in the supernatants of PHA and
      IL-4 cultures. These results show that the modulation of CD23 expression is
      different on B and T cells, and that IFN-gamma acts differently in atopic and non
      atopic individuals.

PMID- 9649192
TI  - P-selectin requirement for neutrophil accumulation and injury in the direct
      passive Arthus reaction.
AB  - The aim of this study was to investigate the role of P-selectin in the
      accumulation of neutrophils in the direct passive Arthus reaction in rat skin.
      Direct passive Arthus dermal reaction was induced in male Sprague-Dawley (SD)
      rats by a single i.v. injection of rat anti-sheep globulin (SG) 1 h before i.d.
      injection of SG antigen. Anti-P-selectin or irrelevant control antibody was given
      1 h before rat anti-SG injection. Complement depletion was also performed in a
      separate group by pretreatment with cobra venom factor (CVF). In all groups
      dermal swelling was assessed 4 h after antigen challenge. Four hours after
      antigen challenge, rats treated with control antibody developed skin swelling
      (2.29 +/- 0.47 mm), prominent complement deposition and neutrophil accumulation.
      This response was associated with local up-regulation of endothelial P-selectin.
      Pre-treatment with anti-P-selectin antibody 1 h before passive Arthus induction
      prevented skin swelling (0.29 +/- 0.06 mm, P < 0.05, cf with control antibody
      treatment), neutrophil accumulation and up-regulation of endothelial P-selectin
      despite complement deposition. CVF treatment prevented complement deposition,
      neutrophil accumulation and skin swelling (0.13 +/- 0.07 mm, P < 0.05, cf with
      saline treatment). However, endothelial P-selectin expression was still present.
      Inhibition of skin swelling and neutrophil accumulation in direct passive Arthus
      by functional inhibition of P-selectin suggest a pivotal role for this adhesion
      molecule in this inflammatory process. These results also suggest that multiple
      steps are involved in the evolution of direct passive Arthus, including both P
      selectin expression and complement activation. However, while complement
      activation is essential for neutrophil accumulation and expression of dermal
      injury, P-selectin up-regulation initiated by antibody/antigen deposition occurs
      independently of complement activation.

PMID- 9649193
TI  - Different susceptibilities of yeasts and conidia of Penicillium marneffei to
      nitric oxide (NO)-mediated fungicidal activity of murine macrophages.
AB  - Penicillium marneffei is an important opportunistic fungal pathogen. Host defence
      mechanisms against P. marneffei are not fully understood. We investigated the
      fungicidal activity of murine peritoneal macrophages against two forms of P.
      marneffei, conidia and yeast cells, and the involvement of the NO-mediated
      killing system. Peritoneal macrophages suppressed the intracellular growth of P.
      marneffei yeast cells and conidia. The number of live yeast cells within
      macrophages was significantly reduced by activation of macrophages by interferon
      gamma (IFN-gamma), while a similar response was not observed with conidia. IFN
      gamma-induced macrophage fungicidal activity against yeast cells was mediated by
      NO and was almost completely inhibited by N(G)-monomethyl-L-arginine (L-NMMA), a
      competitive inhibitor of NO synthesis, while N(G)-monomethyl-D-arginine (D-NMMA),
      an optical isomer of L-NMMA, did not show any influence. NO production by
      macrophages stimulated with IFN-gamma was significantly enhanced when these
      macrophages were cultured with P. marneffei yeast cells, while conidia did not
      enhance macrophage NO production. Furthermore, yeast cells were more susceptible
      to the killing effect of chemically generated NO than conidia. Our results
      indicate that the yeast form of P. marneffei is more sensitive to the fungicidal
      activity of IFN-gamma-stimulated macrophages than conidia, and suggest that the
      different effects of two forms of P. marneffei on macrophage NO production and
      their different susceptibilities to NO may be reasons for the present findings.

PMID- 9649194
TI  - Single-cell analysis of lymphokine imbalance in asymptomatic HIV-1 infection:
      evidence for a major alteration within the CD8+ T cell subset.
AB  - In this study we investigated at single-cell level by flow cytometry the
      potential of T cell cytokine production in asymptomatic HIV-1-infected subjects
      with > 200 CD4 counts and possible correlation with T helper cell depletion and
      viral load. Mitogen-stimulated peripheral blood mononuclear cells from 32 HIV-1+
      patients and 16 healthy subjects were intracytoplasmically stained for IL-2,
      interferon-gamma (IFN-gamma), IL-4 or IL-10, and the frequency of cytokine
      producing cells was assessed in total T cells, CD4, CD8 and CD45RO subsets as
      well as in CD69+CD3+ gated lymphocytes. HIV-1+ patients, irrespective of their
      degree of CD4 depletion, exhibited a major increase in IFN-gamma+ CD8 T cells,
      largely due to CD28- cells, as well as a decrease in the capacity of CD8 T cells
      to produce IL-2. Patients with > 500 CD4 counts showed a diminished frequency of
      IL-4 expression in CD4 T cells and a negative correlation was found between this
      parameter and the ex vivo CD4 counts in the 32 patients. Analysis of patients
      stratified according to viral load revealed a significantly higher proportion of
      IL-2-producing CD4 cells in the group with < 5000 RNA copies/ml. In short, using
      single-cell analysis and an antigen-presenting cell-independent stimulus, we have
      not been able to find any significant cytokine imbalances in the CD4 subset,
      suggesting that the well described T helper defects are not due to intrinsic
      alterations in the potential of CD4 T cells to produce cytokines. On the other
      hand, the major disturbances in the CD8 T lymphocytes agree with the marked
      activation and possible replicative senescence of CD8 T cells and emphasize the
      role of this subset in HIV immunopathogenesis.

PMID- 9649195
TI  - Increased eosinophil activity in acute Plasmodium falciparum infection-
      association with cerebral malaria.
AB  - To assess the eosinophil response to Plasmodium falciparum infection a cohort of
      initially parasite-free Ghanaian children was followed for 3 months. Seven of
      nine children who acquired an asymptomatic P. falciparum infection showed
      increase in eosinophil counts, while a decrease was found in seven of nine
      children with symptomatic malaria, and no change was observed in 14 children who
      remained parasite-free. In a hospital-based study, paediatric patients with
      cerebral malaria (CM), severe anaemia (SA), or uncomplicated malaria (UM) had
      uniformly low eosinophil counts during the acute illness followed by eosinophilia
      30 days after cure. Plasma levels of eosinophil cationic protein (ECP) and
      eosinophil protein X (EPX) were measured as indicators of eosinophil activation.
      In spite of the low eosinophil counts, ECP levels were increased on day 0 and
      significantly higher in patients with CM (geometric mean (95% confidence
      interval) 8.5 ng/ml (6.8-10.7 ng/ml)) than in SA (4.7 ng/ml (3.0-7.5 ng/ml)) and
      UM patients (4.3 ng/ml (3.6-5.3 ng/ml), P < 0.001). A similar pattern was found
      for EPX. It thus appears that the low eosinophil counts may be due to tissue
      sequestration and destruction rather than decreased production. The plasma levels
      of the granule proteins correlated with levels of tumour necrosis factor and
      soluble IL-2 receptor, implicating inflammatory responses and T cell activation
      as causes of the eosinophil activation. By contrast, the eosinophil induction did
      not appear to be part of a Th2-like response. Eosinophil granule proteins may be
      important in both control of malaria infection and the pathogenesis of severe
      malaria.

PMID- 9649196
TI  - Down-regulation of MHC class II molecules and inability to up-regulate class I
      molecules in murine macrophages after infection with Toxoplasma gondii.
AB  - Toxoplasma gondii is able to invade phagocytic cells of the monocyte-macrophage
      lineage and replicates within a parasitophorous vacuole. Since macrophages may
      activate specific T lymphocytes by presenting pathogen-derived antigens in
      association with molecules of the MHC, we investigated the in vitro expression of
      host cell molecules involved in antigen processing and presentation before and
      during infection of murine bone marrow-derived macrophages (BMM) with T. gondii.
      Fifty-one hours after addition of T. gondii tachyzoites at different parasite-to
      host ratios, up-regulation of total MHC class II molecules by interferon-gamma
      (IFN-gamma) was dose-dependently abrogated in up to 50% of macrophages compared
      with uninfected control cultures. Quantitative analyses by flow cytometry
      revealed that the IFN-gamma-induced surface expression of class II antigens as
      well as the IFN-gamma-induced upregulation of class I molecules was significantly
      decreased in T. gondii-infected macrophage cultures compared with uninfected
      controls. However, the constitutive expression of MHC class I antigens was not
      altered after parasitic infection, and infected BMM remained clearly positive for
      these molecules. After infection of macrophages preactivated with IFN-gamma for
      48 h, T. gondii also actively down-regulated an already established expression of
      MHC class II molecules. Furthermore, kinetic analysis revealed that the reduction
      in intracellular and plasma membrane-bound class II molecules started
      approximately 20 h after infection. While MHC class II antigens were most
      prominently reduced in parasite-positive host cells, culture supernatant from T.
      gondii-infected BMM cultures also significantly inhibited expression of these
      molecules in uninfected macrophages. However, down-regulation of MHC class II
      molecules was not mediated by an increased production of prostaglandin E2, IL-10,
      transforming growth factor-beta or nitric oxide by infected BMM compared with
      uninfected controls. Our data indicate that intracellular T. gondii interferes
      with the MHC class I and class II antigen presentation pathway of murine
      macrophages and this may be an important strategy for evasion from the host's
      immune response and for intracellular survival of the parasite.

PMID- 9649197
TI  - Abnormal T cell responses to bacterial superantigens in Behcet's disease (BD).
AB  - This study examines the nature of T cell hypersensitivity in BD. Highly purified
      T cells from 32 BD patients, from 29 rheumatoid arthritis (RA) patients and from
      14 healthy individuals were cultured with various concentrations of
      Staphylococcal enterotoxins (SE) B and C1 in the presence of monocytes for 5
      days, after which the production of interferon-gamma (IFN-gamma) was assessed.
      High concentrations of SE (1 ng/ml) stimulated BD T cells as well as control T
      cells to produce comparably high amounts of IFN-gamma, whereas low concentrations
      of SE (1 pg/ml) stimulated BD T cells much more effectively than normal or RA T
      cells. The hypersensitivity of BD T cells to low concentrations of SEC1 was
      restored with RA monocytes instead of BD monocytes, whereas BD monocytes could
      not elicit the SEC1-induced IFN-gamma production of RA T cells. Moreover, there
      were no significant differences between BD T cells and RA T cells in monocyte
      independent IFN-gamma production stimulated with low or high concentrations of
      immobilized anti-CD3, or in the monocyte-mediated enhancement of IFN-gamma
      production stimulated with a low concentration of immobilized anti-CD3. These
      results confirm that T cell hypersensitivity is not confined to certain specific
      antigens in BD. More importantly, the data strongly suggest that abnormalities in
      signal transduction triggered by perturbation of T cell receptors, but not in
      that induced by cross-linking of CD3 molecules nor in that delivered through
      costimulation molecules, play an important role in the pathogenesis of BD.

PMID- 9649198
TI  - Binding of anticardiolipin antibodies to protein C via beta2-glycoprotein I
      (beta2-GPI): a possible mechanism in the inhibitory effect of antiphospholipid
      antibodies on the protein C system.
AB  - It is known that antiphospholipid antibodies (aPL) hamper the anticoagulant
      activity of the protein C system, but the mechanism is still obscure. In this
      study, we demonstrate that anticardiolipin antibodies (not anti-protein C
      autoantibodies) can bind protein C via beta2-GPI, which bears their binding
      epitope, in a fashion dependent on negatively charged phospholipids. We studied
      the binding of IgG from aPL to protein C in the presence of beta2-GPI by ELISA
      (anti-'protein C' antibody ELISA), and compared their binding with those obtained
      in the absence of beta2-GPI. In the anti-'protein C' antibody ELISA system, 47%
      of 78 aPL+ patients had a positive titre in the presence of cardiolipin (CL) and
      beta2-GPI, but binding was not found in the absence of beta2-GPI. Highly
      significant correlations were found between the titre of anti-'protein C'
      antibody in the presence of beta2-GPI and that of anti-beta2-GPI antibody (r =
      0.802, P = 0.0001). We further analysed the interaction between protein C,
      phospholipids, beta2-GPI and human aCL MoAbs established from patients with
      antiphospholipid syndrome. In a first set of experiments, the binding of beta2
      GPI to protein C and its phospholipid dependency were investigated. Beta2-GPI
      bound to protein C in the presence of CL or phosphatidylserine, but not in the
      presence of phosphatidylcholine or phosphatidylethanolamine. In a second group of
      experiments, the binding of three human monoclonal aCL recognizing the cryptic
      epitope of beta2-GPI (virtually anti-beta2-GPI antibodies) was evaluated in the
      presence of cardiolipin and beta2-GPI. All three human monoclonal aCL bound to
      protein C in the presence of CL and beta2-GPI, whereas they did not in the
      absence of either beta2-GPI or CL. These data suggest that protein C could be a
      target of aCL by making a complex with CL and beta2-GPI, leading to protein C
      dysfunction.

PMID- 9649199
TI  - Effects of granulocyte colony-stimulating factor (G-CSF) treatment on granulocyte
      function and receptor expression in patients with ventilator-dependent pneumonia.
AB  - Considerable experimental evidence in animals suggests that treatment with G-CSF
      may have a beneficial effect in the management of severe infections in non
      neutropenic hosts. This beneficial effect is attributed to an enhancement of
      granulopoiesis and neutrophil function, the latter possibly involving up
      regulation of receptors on neutrophils that are involved in antibody-mediated
      cytotoxicity and killing of microorganisms. We compared neutrophil function and
      phenotype in blood and bronchoalveolar lavage fluid (BALF) of 10 patients with
      severe ventilator-dependent pneumonia, at baseline and following initiation of G
      CSF treatment as adjunct to standard therapy. G-CSF treatment was associated with
      three-fold increased blood neutrophil counts at day 3 of treatment compared with
      baseline counts. Mean serum G-CSF concentration increased from 313 to 2007 pg/ml.
      After correction for lavage dilution effects, BALF G-CSF levels did not differ
      significantly from baseline, nor did neutrophil receptor expression (FcgammaRI,
      FcgammaRII, FcgammaRIII, CR3, and L-selectin) or indicators of neutrophil
      function such as respiratory burst activity, phagocytosis and killing of Candida
      albicans in BALF or blood. The mortality in this group of patients was 30% and
      compared favourably to the APACHE II-derived predicted mortality of 60%. We
      conclude that the possible therapeutic benefit of G-CSF administration in the
      early phase of severe bacterial pneumonia is not readily explained by its effect
      on baseline indicators of neutrophil function or receptor expression.

PMID- 9649200
TI  - Induction of unresponsiveness against IgA in IgA-deficient patients on
      subcutaneous immunoglobulin infusion therapy.
AB  - Patients with IgA deficiency often demonstrate circulating antibodies against
      IgA, which have been suggested to be associated with transfusion reactions. Sera
      from three patients with common variable immunodeficiency (CVID) and one with a
      selective IgA deficiency with anti-IgA antibodies receiving subcutaneous
      gammaglobulin replacement therapy were analysed for serum levels of IgG, IgA and
      anti-IgA before and during a treatment period of 4-7 years. Treatment with
      gammaglobulin preparations containing significant amounts of IgA (< 5 mg/ml)
      resulted in a decrease or disappearance of the anti-IgA antibodies. Analysis of
      serum fractions, however, revealed anti-IgA activity in the complex-containing
      fractions. In vitro experiments gave similar results with a shift of anti-IgA
      activity from the monomeric to the complex-containing fractions (that could not
      be detected in whole serum). When the patients were subsequently switched to
      treatment with a preparation containing less IgA (< 80 microg/ml) or made an
      interruption in the treatment schedule, the anti-IgA antibodies reappeared.
      Importantly, however, one of the patients lost his anti-IgA activity during a 3
      month period on the preparation containing the higher IgA levels, and these
      antibodies did not reappear after switching to the low IgA-containing
      preparation. After 5 years on this preparation, anti-IgA can still not be
      detected, suggesting induction of unresponsiveness.

PMID- 9649201
TI  - Increase in dendritic cell numbers, their function and the proportion uninfected
      during AZT therapy.
AB  - The effects of AZT treatment on the numbers, level of infection and function of
      peripheral blood dendritic cells (DC) were examined in patients with HIV
      infection. This was a cross-sectional study of patients before AZT treatment and
      up to 20 months after initiation of treatment. Numbers of DC separated by density
      gradients were below the normal range in patients before treatment, but increased
      between 3 and 12 months of treatment. The numbers of DC per provirus copy rose
      from around 100 cells to 5000 cells and this decrease in viral load in DC was
      significant between 3 and 20 months of treatment. The capacity of DC to stimulate
      allogeneic T cell proliferation was low before treatment and significantly higher
      between 6 and 12 months after the start of AZT. This study indicated that AZT
      treatment produced beneficial effects on DC by increasing their numbers, reducing
      the provirus load and increasing their function in stimulating T cells. These
      results support the thesis that the function of these potent antigen-presenting
      cells is important in development of immunological defects in AIDS, and that
      effects of AZT treatment on DC may provide a measure of its therapeutic effect.

PMID- 9649202
TI  - Cloning and characterization of a latex allergen (Hev b 7): homology to patatin,
      a plant PLA2.
AB  - We previously identified a 46-kD protein allergen in latex as having amino acid
      sequence homology to the patatin gene family. The objective of this study was to
      characterize this protein by molecular techniques. RNA was isolated from the
      latex or leaf material from Hevea brasiliensis and from potato tubers. Specific
      polymerase chain reaction (PCR) primers were designed from the amino acid
      sequence and reverse transcriptase (RT)-PCR amplified a specific product from
      latex RNA that was subsequently cloned and sequenced. This product was 1493 bp in
      length with an 1167 bp open reading frame. The deduced amino acid sequence
      encodes for a 389 aa protein, pI 4.82 with 43% homology to tobacco patatin.
      Northern analysis of potato, Hevea leaf, and latex RNA demonstrated the message
      to be most abundant in latex, weakly present in Hevea leaf, but no hybridization
      occurred with potato RNA. Patatin has lipid acyl-transferase and PLA2-like
      activity, suggesting it plays a role as a defence-related protein. Other defence
      related proteins in latex such as hevein, glucanase, and hevamine are also
      allergens. Increased production of defence-related proteins as a result of
      increased tapping of the rubber trees to meet the demand for latex may explain
      the increased allergenicity of latex.

PMID- 9649203
TI  - T cell receptor (TCR) Vbeta gene usage in bronchoalveolar lavage and peripheral
      blood T cells from asthmatic and normal subjects.
AB  - T cells are thought to play an important regulatory role in asthma, but little is
      known about the T cell repertoire of the human lung or whether asthma is
      associated with any specific repertoire changes. Flow cytometry and MoAbs to TCR
      VB (TCRBV) families were used to quantify bronchoalveolar lavage (BAL) and blood
      T cells from normal and atopic individuals. Clonality was then assessed by
      polymerase chain reaction (PCR) amplification of cDNA and gene scanning using
      consensus and family-specific TCRBV primers and confirmed by sequence analysis.
      In addition, blood and BAL T cell populations were studied pre- and post-allergen
      challenge in four patients with allergic asthma. The majority of TCRBV families
      detected in blood by MoAb staining were also represented in BAL. While
      differences between BAL and blood populations were evident in each individual
      studied, these differences were not consistent between individuals or between
      CD4+ and CD8+ T cell subpopulations. These results are in broad agreement with
      other published studies, but in contrast to previous work we found a consistent
      difference between TCRBV7 family usage in blood and BAL in all individuals
      studied, and a consistently increased proportion of CD4+ BAL T cells bearing
      BV5S2/3 in asthmatics only. After allergen challenge, the pattern of TCRBV gene
      usage was largely unchanged as judged by flow cytometry. Gene scanning of PCR
      products generated from consensus VB primers revealed polyclonal lymphocyte
      populations in blood and BAL from all seven atopic individuals: in one normal
      tested polyclonal populations were found in blood and oligoclonal populations in
      BAL. Selected families amplified with family-specific primers BV5S2/3, BV6 and
      BV7 (chosen because of their predominance in BAL compared with blood) were more
      variable and revealed predominant polyclonal populations in blood and polyclonal
      or oligoclonal populations in BAL. In one asthmatic patient a clonal BV5S2 family
      was found in BAL. Following allergen challenge there were no significant changes
      in polyclonality/oligoclonality/clonality in three cases, but in one case a
      clonal BV5S2 population was found after challenge, that had not been evident
      beforehand. The lung T cell repertoire is thus broadly representative of blood T
      cells, but shows population differences that may result from response to
      persistent exposure to airborne antigens common to normal and atopic individuals.
      Oligoclonal TCRBV family expansion appears to be primarily lung-specific but
      independent of atopic asthma, although our challenge data in one case support the
      concept that clonal populations may follow local allergen challenge. These data
      are consistent with selection and amplification of specific T cell families in
      the lung in response to local antigenic exposure.

PMID- 9649204
TI  - Immunity to type IX collagen in rodents: a study of type IX collagen for
      autoimmune and arthritogenic activities.
AB  - Type IX collagen (CIX), a cartilage-specific glycoprotein, constitutes < or = 10%
      of cartilage collagen. To ascertain whether CIX can induce arthritis as shown for
      type II and XI collagen (CII and CXI), outbred rats were sensitized with bovine,
      chick and human CIX; inbred rats, mice, and guinea pigs were sensitized with
      bovine CIX. Mice and guinea pigs proved resistant to arthritis, as did rats
      sensitized with CIX/Freund's incomplete adjuvant (FIA). Arthritis was seen in
      rats when 100 microg of Mycobacterium tuberculosis (Mtb) were added to FIA, but
      seldom with smaller doses of Mtb, suggesting the arthritis was adjuvant-induced.
      High levels of antibodies to rat CIX, containing complement-fixing subclasses,
      were detected in rat sera in addition to DTH and lymphocyte proliferation
      responses to rat CIX. Given the potential for CIX-induced disease, CIX-sensitized
      rats were injected intraperitoneally with lipopolysaccharide (LPS) to stimulate
      proinflammatory cytokine release, and intra-articularly with rat CIX to stimulate
      arthritis. LPS stimulation was ineffective; however, intra-articularly injected
      CIX produced transient synovitis. When rats with stable adjuvant arthritis were
      sensitized with CIX/FIA, significant increases in paw volume were measured
      compared with controls given CI/FIA. Immunohistochemical studies of actively and
      passively sensitized rats revealed deposits of CIX antibody, but not C3, at the
      joint margins where proteoglycan staining was weak. Together, these findings
      suggest that autoimmunity to CIX, in contrast to CII and CXI, is not directly
      pathogenic but may contribute to joint injury provided arthritis is initiated by
      an independent disease process.

PMID- 9649205
TI  - Endogenous glucocorticoids modulate neutrophil migration and synovial P-selectin
      but not neutrophil phagocytic or oxidative function in experimental arthritis.
AB  - Pharmacologic glucocorticoids are powerful inhibitors of the inflammatory
      response at many levels, including leucocyte trafficking and function. The
      adhesion molecule P-selectin is a key participant in polymorphonuclear neutrophil
      (PMN) migration to sites of inflammation. The extent to which endogenous
      glucocorticoids influence PMN migration and activation is not clear. We used the
      glucocorticoid receptor antagonist RU486 to examine the effect of endogenous
      glucocorticoid blockade on PMN migration and function in carrageenan
      monoarthritis in the rat. Arthritis was induced by intraarticular injection of
      carrageenan and disease severity measured by PMN count in synovial lavage fluid.
      Decalcified frozen sections of injected joints were analysed for expression of P
      selectin by immunohistochemistry. Adrenal glucocorticoid action was blocked in
      vivo with RU486 20 mg/kg. PMN phagocytosis and reactive oxygen species synthesis
      were measured by flow cytometry. Carrageenan injection was associated with severe
      arthritis (synovial lavage PMN 5.9 +/- 0.7 x 10(6), P < 0.01 versus control)
      which was dose-dependent. P-selectin was not detected in normal joints but was
      abundant in joints injected with 500 microg carrageenan. RU486 resulted in
      exacerbation of carrageenan arthritis (9.7 +/- 0.8 x 10(6), P < 0.05). RU486 also
      altered the threshold for disease induction, in that most RU486-treated animals
      were susceptible to arthritis at a dose of carrageenan (2.5 microg) which did not
      induce arthritis in most control-treated animals (P < 0.05), denoting an altered
      threshold for arthritis induction. RU486 treatment was associated with increased
      synovial P-selectin expression. Activation status as measured by PMN phagocytic
      and oxidative function were not influenced by endogenous glucocorticoid blockade.
      These findings suggest that endogenous glucocorticoids selectively influence PMN
      migration to inflamed joints via P-selectin expression, but have no effect on PMN
      activation status.

PMID- 9649206
TI  - Augmented levels of macrophage and Th1 cell-related cytokine mRNA in
      submandibular glands of MRL/lpr mice with autoimmune sialoadenitis.
AB  - MRL/Mp-lpr/lpr (MRL/lpr) mice spontaneously develop destructive inflammation of
      the salivary and lachrymal glands resembling Sjogren's syndrome (SS),
      representing an animal model to study this disease. We used in situ hybridization
      with synthetic radiolabelled oligonucleotide probes to examine expression of mRNA
      encoding pro- and anti-inflammatory cytokines in submandibular glands of 2, 3, 4
      and 5-month-old MRL/lpr mice. Phenotypic composition of submandibular gland
      infiltrates was evaluated by immunohistochemistry. Cells expressing tumour
      necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6 and IL-12 mRNA were strongly up
      regulated at about the time of onset of sialoadenitis, suggesting a role of these
      cytokines in development of the disease. Interferon-gamma (IFN-gamma) and
      cytolysin mRNA-expressing cells were gradually up-regulated over the disease
      course up to 5 months of age, the time when sialoadenitis is at its height,
      favouring a role of these cytokines in progression of the disease as well. Low
      levels of IL-10 and transforming growth factor-beta (TGF-beta) mRNA-expressing
      cells were observed at 2, 3 and 4 months of age, and were almost undetectable at
      5 months. Maximum levels of CD4+, CD8+ and interdigitating/dendritic cells, as
      well as of MHC class II and MHC class I expression were seen at 3 months, with
      CD4+ outnumbering CD8+ cells. Maximum levels of macrophages were seen at 4 months
      of age. These data argue for a major role of the proinflammatory cytokines TNF
      alpha, IL-1beta, IL-6, IL- 12, IFN-gamma and cytolysin in initiation and
      perpetuation of autoimmune sialoadenitis in MRL/lpr mice, probably in conjunction
      with an insufficiency of the anti-inflammatory cytokines TGF-beta and IL-10.

PMID- 9649207
TI  - IL-6 receptor blockage inhibits the onset of autoimmune kidney disease in NZB/W
      F1 mice.
AB  - In the present study, we examined the preventive effect of anti-mouse IL-6
      receptor (IL-6R) antibody, MR16-1, on the development of autoimmune kidney
      disease in female NZB/W F1 (BWF1) mice. Immunological tolerance to MR16-1 or
      isotype-matched control antibody, KH-5, was induced by the simultaneous
      administration of anti-CD4 MoAb in mice. Thereafter, mice were intraperitoneally
      given 0.5 mg of MR16-1, 0.5 mg of KH-5 or saline once a week from 13 to 64 weeks
      of age. MR16-1 treatment dramatically suppressed proteinuria and prolonged the
      survival time of BWF1 mice. Only one out of 10 mice died with high levels of
      proteinuria throughout the experiment. MR16-1 almost completely suppressed the
      production of IgG forms of anti-DNA and anti-TNP antibodies, but not the IgM
      forms of these antibodies. In particular, all IgG subclasses (IgG1, IgG2a, IgG2b
      and IgG3) of anti-DNA antibody production were significantly suppressed.
      Moreover, serum IgG1, IgG2a and IgG3 levels in MR16-1-treated mice were lower
      than those in saline- and KH-5-treated mice, whereas serum IgM and IgA levels
      were not influenced. In conclusion, MR16-1 potently suppressed the development of
      autoimmune disease in BWF1 mice, and this was attributed to its effect of
      specific suppression of IgG class antibody production.

PMID- 9649208
TI  - Tumour-specific cytotoxic T lymphocyte activity in Th2-type Sezary syndrome: its
      enhancement by interferon-gamma (IFN-gamma) and IL-12 and fluctuations in
      association with disease activity.
AB  - Sezary syndrome (SzS) is the leukaemic variant of cutaneous T cell lymphoma
      (CTCL), whose malignant T cells are of the Th2 type in most cases. In this study
      we investigated the tumouricidal activity of cytotoxic T lymphocytes (CTL)
      present in peripheral blood of a patient with Th2-type SzS, focusing on the
      effect of IL-2, IFN-gamma and IL-12 on their cytotoxic activity, and the
      relationship between their lytic capacity and the patient's clinical course. At
      four different time points during a 2-month clinical period, CD4+CD7- Sezary
      cells and CD8+ cells were separated from the patient's circulating cells. CD8+
      cells were cultured with chemically attenuated, purified Sezary cells in the
      presence of IL-2 to develop specific cytotoxicity. The CD8+ cells thus cultured
      exhibited lytic activity against autologous Sezary cells. Concomitant addition of
      IFN-gamma or IL-12 exerted a synergistic cytolytic effect with IL-2 on the tumour
      cells. Cytotoxicity inhibition studies using MoAbs revealed that the cytotoxicity
      operated in MHC class I-, CD8- and alphabeta T cell receptor-dependent manners.
      Furthermore, eight CD8+ T cell clones generated from cultured CD8+ cells
      exhibited a strong cytotoxicity against Sezary cells in an MHC class I-restricted
      fashion. During the clinical course, the activity of generated CTL and the number
      of CD8+ cells were inversely correlated with disease activity as assessed by the
      serum level of lactate dehydrogenase. These findings suggest that CTL down
      regulate the growth of malignant T cells in this long-standing disease. Since Th2
      cytokines such as IL-4 down-modulate CTL activity, CTL are assumed to be usually
      suppressed in SzS, whose malignant T cells are of Th2 type. It is likely that the
      administration of IFN-gamma normalizes this Th2-skewing state, activates CTL, and
      thus exerts the therapeutic effectiveness in the treatment of CTCL.

PMID- 9649209
TI  - Normal and clonal B lineage cells can be distinguished by their differential
      expression of B cell antigens and adhesion molecules in peripheral blood from
      multiple myeloma (MM) patients--diagnostic and clinical implications.
AB  - Human MM is a haematologic disorder characterized by the accumulation of
      malignant plasma cells (PC), primarily in the bone marrow (BM). Although these
      cells characteristically home to the BM, in recent years several groups have
      detected the presence of related malignant B cells in the peripheral blood (PB)
      which could be implicated in the progression and spread of the disease. However,
      the proportion and origin of these clonotypic circulating B cells is still
      controversial. In this study, using a triple-staining flow cytometric procedure
      and a whole blood lysis method, PB B lineage cells could be divided into two
      populations according to their distinct repertoires of cell adhesion molecules
      and B cell antigens in untreated MM patients. The results show that: (i) the
      percentage and the absolute number of PB CD19+ B cells were decreased in MM
      patients compared with controls; (ii) the quantity and percentage of B cell
      antigens (CD20, CD22, CD24, DR, CD138) and adhesion molecules (beta1- and beta2
      integrins, CD44, CD54, CD56, CD61 and CD62L) expressed by these PB CD19+ cells of
      MM patients and healthy subjects were similar and all of them were virtually
      polyclonal cells; (iii) a very minor circulating CD19-CD38++CD45-/dim subset was
      also detected which expressed CD138 (B-B4) (high intensity), monoclonal
      cytoplasmic immunoglobulin (cIg), and was negative for pan-B antigens (CD19,
      CD20, CD24, DR), surface immunoglobulin (sIg) and several adhesion molecules such
      as CD62L, CD18 and CD11a; this CD19-CD38++CD45-/dim CD138++ subset was not found
      in normal blood and exhibited a phenotypic profile which was closely related to
      that of malignant BM plasma cells, with the exception of the CD56 antigen.
      Polymerase chain reaction (PCR) analysis of IgH clonotypic rearrangements
      confirmed these results. We postulate that, in MM patients, circulating B lineage
      cells may be divided into two different categories: polyclonal CD19+ B cells and
      a very minor proportion of clonal CD138++ PC that escape from the BM.

PMID- 9649210
TI  - Neoplastic thymic epithelial cells of human thymoma support T cell development
      from CD4-CD8- cells to CD4+CD8+ cells in vitro.
AB  - Human thymoma is a thymic epithelial cell tumour which often contains a large
      number of immature T cells and is frequently associated with autoimmune diseases.
      Since thymic epithelial cells play key roles in the development and selection of
      T cells in the normal thymus, we hypothesized that the neoplastic thymic
      epithelial cells of thymoma may support T cell differentiation in the tumour. We
      characterized CD4-CD8- cells in thymoma and applied an in vitro reconstitution
      culture system using the CD4-CD8- cells and the neoplastic epithelial cells
      isolated from thymoma. CD34, a stem cell marker, was expressed on 29.9 +/- 12.2%
      of CD4-CD8- cells in thymoma. TCRgammadelta was expressed on 27.4 +/- 15.1% of
      CD4-CD8- cells and CD19, a B cell marker, was expressed on 14.1 +/- 23.1% of CD4
      CD8- cells. CD4-CD8- cells expressed both IL-7R alpha-chain and common gamma
      chain. Purified CD4-CD8- cells from thymomas were cultured with the neoplastic
      epithelial cells, and their differentiation into CD4+CD8+ cells via CD4 single
      positive intermediates was observed within 9 days' co-culture in the presence of
      recombinant IL-7. Furthermore, we examined the reconstitution culture using
      CD34+CD4-CD8- cells purified from normal infant thymus. The CD34+CD4-CD8- cells
      in normal thymus also differentiated to CD4+CD8+ cells in the allogeneic co
      culture with the neoplastic epithelial cells of thymoma. These results indicate
      that the tumour cells of thymoma retain the function of thymic epithelial cells
      and can induce differentiation of T cells in thymoma.

PMID- 9649211
TI  - Analysis of orbital T cells in thyroid-associated ophthalmopathy.
AB  - Thyroid-associated ophthalmopathy (TAO) has a major effect on the two
      compartments of the retro-orbital (RO) space, leading to enlargement of the
      extraocular muscles and other RO tissues. T lymphocyte infiltration of RO tissue
      is a characteristic feature of TAO and there is current interest in whether these
      T cells are specifically and selectively reactive to RO tissue itself. We
      recently established 18 T cell lines (TCL) from RO adipose/connective tissue of
      six patients with severe TAO by using IL-2, anti-CD3 antibodies and irradiated
      autologous peripheral blood mononuclear cells (PBMC) to maintain the growth of T
      cells reactive to autologous RO tissue protein fractions. Here we report on the
      phenotype characteristics and cytokine gene expression profiles of these orbital
      TCL and on their immunoreactivity to the organ-specific thyroid antigens
      thyrotropin receptor (TSH-R), thyroidal peroxidase (TPO) and thyroglobulin (TG).
      Flow cytometry revealed that 10 TCL were predominantly of CD4+ phenotype, three
      being mostly CD8+ and five neither CD4+ nor CD8+. Analysis with reverse
      transcriptase-polymerase chain reaction (RT-PCR) of cytokine gene expression
      revealed both Th1- and Th2-like products in all TCL: IL-2 product (in 17 TCL),
      interferon-gamma (IFN-gamma) (n = 10), tumour necrosis factor-beta (TNF-beta) (n
      = 15), IL-4 (n = 12), IL-5 (n = 17), IL-6 (n = 13), TNF-alpha (n = 12) and IL-10
      (n = 4). Reactivity to thyroid antigens was observed only in two TCL, the other
      16 being uniformly unreactive. Although 10 out of 18 RO tissue-reactive TCL were
      predominantly CD4+ there were no significant relationships between TCL phenotype,
      cytokine gene profile, magnitude of reactivity to RO tissue protein or the (rare)
      occurrence of thyroid reactivity. The findings of both Th1- and Th2-like cytokine
      gene expression in all RO tissue-reactive TCL support the concept that TAO is a
      tissue-specific autoimmune disease, distinct immunologically from the thyroid,
      and involving both T cell and B cell autoimmune mechanisms in disease
      pathogenesis.

PMID- 9649213
TI  - A pancolitis resembling human ulcerative colitis (UC) is induced by CD4+ TCR
      alphabeta T cells of athymic origin in histocompatible severe combined
      immunodeficient (SCID) mice.
AB  - CD4+ TCRalphabeta+ T cells from the colonic lamina propria of athymic (nude) mice
      were adoptively transferred into histocompatible (SCID) mice homozygous for the
      autosomal recessive mutation scid (severe combined immunodeficiency). Transfer of
      these extrathymic CD4+ T cells into SCID mice induced a pancolitis in the
      adoptive host. The histopathology of this inflammatory response was restricted to
      the colon and closely resembled human UC. CD4+ T cells infiltrating the colonic
      lamina propria of diseased SCID mice displayed the surface phenotype of mucosa
      seeking memory/effector cells, expressed interferon-gamma (IFN-gamma), and lysed
      targets in a Fas (CD95)/FasL-dependent pathway. Massive accumulation of
      oligoclonal CD4+ T cells of athymic origin with the phenotype of Th1
      memory/effector T cells in the colonic lamina propria of a histocompatible,
      immunodeficient host elicits a pancolitis that morphologically mimics human UC.

PMID- 9649212
TI  - Colonic explant production of IL-1and its receptor antagonist is imbalanced in
      inflammatory bowel disease (IBD).
AB  - IBD is associated with an increased activation of intestinal immune cells, which
      causes overproduction of proinflammatory cytokines such as IL-1beta. IL-1beta is
      implicated in mediating the sustained inflammatory response. IL-1 receptor
      antagonist (IL-1Ra), the naturally occurring inhibitor of IL-1, has been shown to
      have beneficial effects in experimental models of colitis. In this study we
      investigated the hypothesis that an imbalance between IL-1 and IL-1Ra exists in
      IBD by measuring their secretion by explant cultures of colonic biopsies. Freshly
      homogenized biopsies from involved tissue in IBD patients exhibited significantly
      lower IL-1Ra/IL-1beta ratios than control and uninvolved IBD mucosal tissue.
      Using explant cultures, in vitro production of IL-1beta and IL-1Ra increased
      progressively during the 4-18-h culture periods. IL-1beta secretion was higher in
      supernatants from involved Crohn's disease (CD) and ulcerative colitis tissue
      compared with control tissue, and IL-1beta levels increased with severity of
      inflammation. IL-1Ra secretion was not elevated in involved IBD samples, but
      significantly higher levels were released when moderate to severely involved
      tissue samples were compared with noninflammatory controls. Similar to freshly
      homogenized tissue, explant studies showed that the IL-1Ra/IL-1beta ratios were
      significantly decreased in involved IBD tissue, but not in uninvolved CD or
      inflammatory control specimens. These data support the hypothesis of an imbalance
      between IL-1beta and IL-1Ra in IBD.

PMID- 9649214
TI  - Detection and characterization of antibodies specific to food antigens (gliadin,
      ovalbumin and beta-lactoglobulin) in human serum, saliva, colostrum and milk.
AB  - Antibodies against food antigens are usually produced in healthy people. This
      humoral response can be detected both in serum and secretions. The
      characterization of this response can be useful for a better understanding of
      food-related immunological alterations. In this study, IgA and IgG antibodies
      specific to ovalbumin, beta-lactoglobulin or gliadin were measured in serum,
      saliva, colostrum and milk from 40 healthy breast-feeding women. Specific IgA and
      IgG to the three antigens were measured by indirect ELISA. Specific IgG levels
      were highest in serum and very low in the other biological fluids. No correlation
      between the IgG specific to the different antigens was found. Specific IgA
      reactivity was found in all the samples analysed. Levels observed were higher in
      colostrum and milk than in serum and saliva. In spite of being three different
      unrelated food antigens, a correlation between the levels of specific IgA was
      found in saliva, colostrum and milk samples of all subjects studied. The
      specificity of IgA anti-gliadin antibodies from serum, saliva and colostrum was
      analysed by immunoblotting of SDS-PAGE-separated wheat proteins. Each sample
      presented a unique pattern of recognition. No common pattern of recognition was
      found either among the same biological fluids of the different subjects tested,
      or among the different samples--either serum, colostrum or saliva--of the same
      individual. Different degrees of specificity to wheat proteins among IgA from
      colostrum, saliva or serum were observed, suggesting that the local IgA-producing
      populations are functionally different in the different tissues of the organism.

PMID- 9649215
TI  - Cytokine-enhanced mixed lymphocyte reaction (MLR) in cord blood.
AB  - Although in cord blood (CB) transplantation graft-versus-host disease (GVHD) is
      reported to be less severe, GVHD may occur even in patients with HLA-identical
      sibling donors. This result shows that HLA typing can not entirely predict GVHD.
      The standard MLR with CB cells was either normal or slightly reduced compared
      with adult peripheral blood (PB) cells. We used two manipulations to increase the
      responses of CB cells to allo-antigens. The first was to treat the stimulator
      cells with cytokines, and the second to amplify weak proliferative responses by
      adding exogenous cytokines to MLR cultures (modified MLR). The stimulator cells
      were treated with both interferon-gamma (IFN-gamma) and IL-4. The responder cells
      were treated with both IL-2 and tumour necrosis factor-alpha (TNF-alpha). It is
      still to be determined whether or not this cytokine-enhanced MLR could be a
      possible predictor of GVHD. However, using these cytokines, 90% of CB could
      recognize allo-antigens, even if the standard MLR was negative.

PMID- 9649216
TI  - Stimulation with thromboxane A2 (TXA2) receptor agonist enhances ICAM-1, VCAM-1
      or ELAM-1 expression by human vascular endothelial cells.
AB  - A previous study reported that intercellular adhesion molecule-1 (ICAM-1)
      expression by human vascular endothelial cells (HUVEC) is augmented by
      intracellular signal transmission mainly through the protein kinase C (PKC)
      system stimulated by TXA2 receptors. In the present study, we show that a TXA2
      receptor agonist, U46619, augments the expression of not only ICAM-1, but also
      vascular cell adhesion molecule-1 (VCAM-1) or endothelial leucocyte adhesion
      molecule-1 (ELAM-1) in HUVEC both at protein and mRNA levels. Pretreatment with
      SQ29,548 (a TXA2 receptor antagonist) or PKC inhibitors greatly diminished the
      extent of U46619-induced mRNA accumulation and surface expression of the adhesion
      molecules. An inhibitor of nuclear factor kappaB (NF-kappaB) activation, PDTC,
      diminishes U46619-induced VCAM-1 mRNA accumulation. NAC, which inhibits NF-kappaB
      and activation protein 1 (AP-1) binding activity, inhibits the expression of ICAM
      1 or ELAM-1 at protein and mRNA levels. These findings suggest that ICAM-1 or
      ELAM-1 expression of HUVEC stimulated via TXA2 receptors is augmented by
      induction of NF-kappaB and AP-1 binding activity through the PKC system, and that
      VCAM-1 expression is augmented by induction of NF-kappaB binding activity.

PMID- 9649217
TI  - Autoantibody prevalence in children with liver disease due to chronic hepatitis C
      virus (HCV) infection.
AB  - HCV infection and interferon-alpha (IFN-alpha) therapy have been associated with
      autoimmunity. To assess whether chronic liver disease (CLD) due to HCV infection
      or its treatment with IFN-alpha cause autoimmune manifestations, the prevalence
      of tissue autoantibodies in 51 children with chronic HCV infection and 84 with
      other CLD was analysed by standard techniques. Sixty-five percent of patients
      with chronic HCV infection, 66% with chronic hepatitis B infection and 60% with
      Wilson's disease were positive for at least one autoantibody. In the 51 subjects
      with chronic HCV infection (29 treated with IFN-alpha, 22 untreated), tested on
      165 occasions over a median of 9 months (range 5-42 months), autoantibodies to
      nuclei (ANA), smooth muscle (SMA), gastric parietal cell (GPC) and/or liver
      kidney microsomal type 1 (LKM-1) were similarly prevalent in treated and
      untreated patients (90% versus 68%, P = 0.12). Positivity for SMA was present in
      67%, GPC in 32%, ANA in 10%, LKM-1 in 8% of cases. Treatment with IFN-alpha had
      to be suspended due to transaminase elevation in one SMA-positive, one ANA
      positive but in three of four LKM-1-positive patients. Our results show that: (i)
      autoantibodies are common in viral-induced hepatitis and Wilson's disease; (ii)
      positivity for SMA, GPC, ANA is part of the natural course of chronic HCV
      infection, their prevalence being unaffected by IFN-alpha; and (iii) IFN-alpha
      should be used cautiously in the treatment of LKM-1/HCV-positive patients.

PMID- 9649218
TI  - Production of cytotoxic factor by peripheral blood mononuclear cells (PBMC) in
      patients with dengue haemorrhagic fever.
AB  - A unique cytokine, human cytotoxic factor (hCF), has been shown to occur in the
      sera of patients with dengue fever (DF) and dengue haemorrhagic fever (DHF). The
      present study was undertaken to investigate the ability of fresh PBMC of such
      patients to produce hCF. The PBMC were cultured for 24 h and the culture
      supernatants (CS) were analysed for the presence of hCF by cytotoxicity assay,
      competitive ELISA and dot blot tests. In 90% of 246 cases CS were positive for
      hCF by the three tests. CS were positive for hCF in PBMC collected from days 1-20
      of illness but not at later periods. Higher cytotoxic activity was observed in CS
      of days 1-4 of illness and was highest in cases of DHF grade IV and lowest in
      cases of DF. Dot blot hybridization of RNA extracted from the PBMC of the
      patients showed the presence of mRNA for hCF in 94% of cases. A similar number of
      patients showed the presence of hCF in situ in the PBMC smears by fluorescent
      antibody technique. hCF was found only in CD4+ T cells. The findings thus present
      direct evidence of the production of hCF by CD4 T cells of cases of DF/DHF.

PMID- 9649219
TI  - The human autoantigen La/SS-B accelerates herpes simplex virus type 1 replication
      in transfected mouse 3T3 cells.
AB  - Permanently transfected mouse cell lines which expressed different levels of the
      human autoantigen La/SS-B were infected with different strains of herpes simplex
      virus type 1, including the strains ANG, HSZP, 17syn+ and HFEM. During infection
      the localization of the human La protein was followed using an anti-La MoAb,
      which recognized only the human La protein but did not cross-react with either
      the endogenous mouse La protein or any viral encoded protein. After infection La
      protein was transported from the nucleus to the cytoplasm. The time course of
      translocation was dependent on the amount of human La protein expressed in the
      respective cell line. Moreover, acceleration of viral replication was dependent
      on the level of expression of human La protein, suggesting that La protein is a
      cellular factor that facilitates virus replication.

PMID- 9649220
TI  - Circulating antibodies to the 60-kD heat shock protein (hsp) family in patients
      with Helicobacter pylori infection.
AB  - Whilst the mechanism by which Helicobacter pylori causes different gastroduodenal
      diseases is uncertain, strains producing the cytotoxin-associated protein (CagA)
      have greater pathogenicity. Hsps are immunogenic molecules induced by
      inflammatory mediators. The aim of this study was to assess pathogenicity of hsp
      antibodies in H. pylori-infected patients. ELISA techniques were used to assay
      sera of H. pylori-positive patients with gastritis, gastric atrophy, duodenal or
      gastric ulcer, and H. pylori-negative controls, for antibodies to CagA and to
      human, mycobacterial, and in 20 sera, H. pylori (hspB) 60-kD hsp. IgA antibodies
      to mycobacterial hsp60 in atrophy patients were elevated compared with patients
      with gastritis (P < 0.05) and with H. pylori-negative controls (P < 0.0005). IgA
      antibodies to human hsp60 in gastric atrophy patients were elevated compared with
      H. pylori-negative controls (P < 0.05). Patients with atrophy (P < 0.0005) and
      gastritis (P < 0.05) who were CagA-positive had raised titres of anti
      mycobacterial hsp60 IgA antibodies compared with controls. IgA antibody levels to
      hspB were positively correlated with those to mycobacterial hsp60 (mhsp60) (P <
      0.05) and human hsp60 (hhsp60) (P < 0.005). IgA antibodies to hsp60 are
      associated with gastroduodenal disease, particularly gastric atrophy, in H.
      pylori-infected patients. Increased humoral responses to hsp60 could either
      contribute to gastric atrophy or result from greater gastric mucosal damage
      induced by CagA-positive strains of H. pylori.

PMID- 9649221
TI  - Deoxyspergualin preferentially inhibits the growth and maturation of anti-CD40
      activated surface IgD+ B lymphocytes.
AB  - Deoxyspergualin (DSG), an analogue of spermidin, is a potent immunosuppressive
      drug with an action quite distinct from that of cyclosporin, rapamycin, or FK506.
      In this study we investigated the effect of DSG and methyldeoxyspergualin (MeDSG)
      on the proliferation and differentiation of human B cells stimulated with anti
      CD40 MoAb. Highly purified B cells obtained from tonsillar samples were used as
      target cells. Both agents inhibited the proliferative response of anti-CD40
      stimulated B cells in the absence and presence of IL-4, IL-2 or IL-10 in a dose
      dependent manner. This inhibitory effect differed markedly among cell populations
      based on surface IgD expression: strong inhibition of sIgD+ B cells but little
      inhibition of sIgD- B cells. The drugs also suppressed the production of IgG, IgM
      and IgA by unfractionated B cells, which suggests that DSG acts against post
      switch (sIgD-) B cells. Although the drugs suppressed immunoglobulin synthesis by
      both sIgD+ and sIgD- B cells, the effect was more marked in the sIgD+ B cells.
      Analysis of the subclass of IgG secreted by sIgD+ B cells revealed a decline in
      IgG1 and IgG3 in the presence of DSG. These results suggest that DSG
      preferentially inhibits the growth and maturation of sIgD+ naive B cells.

PMID- 9649222
TI  - Selective depletion of CD14+ CD16+ monocytes by glucocorticoid therapy.
AB  - Glucocorticoids (GC) are potent anti-inflammatory and immunosuppressive agents
      that act on many cells of the body, including monocytes. Here we show that a 5
      day course of high dose GC therapy differentially affected the CD14++ and the
      CD14+ CD16+ monocyte subpopulations in 10 patients treated for multiple
      sclerosis. While the classical (CD14++) monocytes exhibited a substantial
      increase from 495 +/- 132 to 755 +/- 337 cells/microl, the CD14+ CD16+ monocytes
      responded with a pronounced decrease from 36 +/- 15 to 2 +/- 3 cells/microl (P <
      0.001). In 4/10 patients the CD14+ CD16+ monocytes fell below detection limits
      (<0.2 cells/microl). This observation was confirmed when the CD14+ CD16+
      monocytes were identified by virtue of their low CD33 expression as these cells
      decreased as well. After discontinuation of GC therapy the CD14+ CD16+ monocytes
      reappeared and reached normal levels after 1 week. The profound depletion of
      CD14+ CD16+ monocytes by GC as described here is a novel effect of GC action in
      vivo and may contribute to GC-mediated immunosuppression. Determination of the
      number of this monocyte subset may also serve to monitor the effectiveness of GC
      therapy in patients requiring immunosuppressive treatment.

PMID- 9649223
TI  - Identification and characterization of autoantibodies against catalase and alpha
      enolase in patients with primary sclerosing cholangitis.
AB  - Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of
      unknown aetiology. Recent studies have shown that genetic factors and both
      cellular and humoral immunological abnormalities are important in the
      pathogenesis of PSC. The most prominent autoantibodies in PSC are anti-neutrophil
      cytoplasmic antibodies (ANCA). The autoepitopes of ANCA in PSC are not well
      defined. The aim of this study was to identify corresponding ANCA autoantigens in
      patients with PSC. A biochemical approach with enrichment and partial
      purification of soluble neutrophil proteins, detection of autoantibodies by
      Western blot and partial amino acid sequencing were used. Two new
      autoantigen/autoantibody systems in patients with PSC were detected: catalase and
      alpha-enolase. The presence of catalase autoantibodies in 9/15 (60%) and alpha
      enolase autoantibodies in 4/15 (27%) was confirmed by ELISA and Western blot.
      Furthermore, we showed immunoreactions of PSC sera with human biliary epithelial
      cells, showed the reduction of fluorescence in anti-catalase absorption
      experiments and observed partial co-localization of anti-catalase antibodies and
      PSC sera in double-staining experiments on biliary epithelial cells. The anti
      catalase antibody-positive PSC patients had a more severe course of disease with
      a significantly higher alkaline phosphatase compared with the anti-catalase
      negative PSC patients (P < 0.06). All ulcerative colitis control sera were anti
      catalase antibody-negative. The identified antigens catalase and alpha-enolase
      can partly explain the ANCA fluorescence on ethanol-fixed and formaldehyde-fixed
      granulocytes in patients with PSC. Catalase is an important anti-oxidant enzyme
      and prevents cell damage from highly reactive oxygen-derived free radicals.
      Catalase autoantibodies might play a pathogenic role in patients with PSC. Our
      findings support the hypothesis that oxidative stress is one of the pathogenic
      mechanisms in patients with PSC.

PMID- 9649224
TI  - VH usage and somatic hypermutation in peripheral blood B cells of patients with
      rheumatoid arthritis (RA).
AB  - The human antibody repertoire has been demonstrated to have a marked V-gene
      dependent bias that is conserved between individuals. In RA patients, certain
      heavy chain V genes (VH) have been found to be preferentially used for encoding
      autoantibodies. To determine if such preferential use of VH genes in
      autoantibodies is associated with a general distortion of the V gene repertoire
      in RA patients, the VH composition of peripheral blood B cells was analysed among
      four RA patients and four age- and sex-matched healthy controls. Usage of
      individual VH genes (eight VH3 and three VH4 genes tested by hybridization with a
      set of gene-specific oligonucleotide probes) was highly biased among RA patients,
      but no evidence of a distortion in the bias was observed compared with healthy
      controls. However, the occurrence of somatic mutations in these VH genes
      (estimated by differential hybridization with motif-specific oligonucleotide
      probes targeted to CDR and FR of the tested genes, and by DNA sequence analysis)
      was strikingly different between patients and healthy subjects. The number of VH3
      rearrangements that had accumulated somatic mutations and the number of mutations
      per rearrangement were significantly elevated in three of the four RA patients. A
      slight but not significant elevation in mutations among rearranged VH4 genes was
      also observed in these patients. These data suggest that although usage of
      individual VH genes among peripheral blood B cells is not affected by the
      disease, the autoimmune process may involve a significant fraction of the B cell
      compartment.

PMID- 9649225
TI  - IL-10 and IL-4 co-operate to normalize in vitro IgA production in IgA-deficient
      (IgAD) patients.
AB  - In the present study we evaluated in vitro immunoglobulin production from IgAD
      individuals and healthy controls. Peripheral blood mononuclear cells (PBMC) from
      IgAD and controls were cultured with anti-CD40 MoAb presented on a CDw32
      transfected fibroblast cell line (CD40 system) in the presence of IL-10, IL-2, IL
      4, transforming growth factor-beta (TGF-beta) alone as well as of IL-10 in
      combination with each of the other three cytokines. Only IL-10 added alone
      induced significant changes in baseline immunoglobulin production; marked
      increases in median supernatant levels of all three isotypes were observed in
      both groups. The most striking finding of this study was the synergizing effect
      of IL-4 on IgA production in the IgAD group when added with IL-10; median IgA
      supernatant level increased to a value superimposable on that found in the normal
      controls which remained about the same as when stimulated with IL-10 alone. The
      synergic effect of IL-4 and IL-10 was specific to the IgA isotype.

PMID- 9649226
TI  - Detection of Fcgamma receptors on human endothelial cells stimulated with
      cytokines tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN
      gamma).
AB  - This investigation was conducted to detect Fcgamma receptors (FcgammaR) on
      cytokine-stimulated human endothelial cells (EC) by measuring anti-FcgammaR MoAb
      binding with an ELISA. TNF-alpha and IFN-gamma significantly increased the
      expression of FcgammaR type II (FcgammaRII) and type III (FcgammaRIII) on aortic
      EC. Simultaneous treatment with both cytokines had a synergistic effect and
      pretreatment of EC with IFN-gamma augmented the effect of TNF-alpha. The greatest
      effect was the increase (up to four-to-six-fold) in expression of FcgammaRII
      found by the simultaneous treatment of aortic EC with both cytokines. The
      receptors were expressed on the cell surface and showed receptor capping after
      incubation at 37 degrees C. This study showed that the inflammatory cytokines TNF
      alpha and IFN-gamma enhanced low-affinity FcgammaR expression on human EC in
      vitro. The expression of FcgammaR may contribute to the specific localization of
      circulating immune complexes on blood vessels in areas of vasculitis.

PMID- 9649227
TI  - T lymphocyte responses to anti-neutrophil cytoplasmic autoantibody (ANCA)
      antigens are present in patients with ANCA-associated systemic vasculitis and
      persist during disease remission.
AB  - ANCA with specificity for myeloperoxidase (MPO) and proteinase 3 (PR3) are
      present in patients with systemic vasculitis. The aim of this work was to
      determine whether such patients have T cell responses to these antigens and
      whether these responses are related to disease activity. Peripheral blood
      lymphocytes from 45 patients and 19 controls were cultured with ANCA antigens and
      proliferation measured. The antigens used were heat-inactivated (HI) MPO, HI PR3,
      native (non-HI) PR3, HI whole alpha-granules, and 25 overlapping peptides
      covering the entire PR3 sequence. Significant responses to both whole PR3
      preparations were seen from patient and control groups, and to the alpha-granules
      from the patient group. Patients responded at all stages of disease: active,
      remitting, treated or untreated. Only two patients responded significantly to
      MPO. Responses were significantly higher with the patient group than the control
      group to all four whole ANCA antigens. Responses to those PR3 peptides containing
      epitopes known to be recognized by ANCA were detected from one patient. Thus,
      these studies demonstrate that T cells from vasculitis patients can proliferate
      to PR3 and occasionally to associated ANCA antigens. Further, responses may
      persist even after disease remission has been achieved.

PMID- 9649228
TI  - Biologic foundation of the therapy for advanced germ cell tumors.
AB  - An understanding of the elements that have contributed to the remarkable cure
      rate in patients with germ cell cancers is a useful exercise for clinicians. The
      prevailing view is that the introduction of chemotherapy was largely responsible
      for this remarkable success. Although chemotherapy is clearly the required
      ingredient, there are other important contributing factors that were essential
      for the high cure rate. These contributing elements include the understanding of
      the biology of the cancer and the availability markers. The understanding of the
      clinical biology and ability to assay persistent minimal cancer led to the
      appropriate integration of systemic and local therapies. The treatment of germ
      cell cancers is the paradigm of multidisciplinary therapy of cancer because it
      accommodates many variables into the clinical decision-making process.

PMID- 9649229
TI  - Integration of surgery and systemic therapy: results and principles of
      integration.
AB  - Eight hundred seventy patients with metastatic nonseminomatous germ cell cancer
      underwent postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for
      resection of residual disease. Several risk factors for relapse and survival were
      identified as highly significant (P = .00001), namely, presence of residual
      cancer in the specimen before salvage chemotherapy programs, tumor marker
      elevation, need for "re-do" PC-RPLND, or unresectability. Although more than half
      of the entire group (52.5%) had one or more of these risk factors, 67.5% are long
      term survivors following PC-RPLND. The remaining 47.5% were referred after
      primary chemotherapy, without risk factors. Only 9.8% relapsed and 95.5%
      survived.

PMID- 9649230
TI  - Testicular tumors: clinically relevant histological findings.
AB  - Testicular germ cell neoplasms affect young men in the prime of life. Although
      the overwhelming majority are malignant, they are curable. In addition to the
      stage of the disease and the presence of serum markers, there are important
      pathological changes that have clinical significance. These include (1) the cell
      type, (2) the amount of the component, and (3) the presence or absence of
      vascular invasion. Pure embryonal carcinoma or embryonal carcinoma in excess of
      80% in a mixed tumor and vascular/lymphatic invasion are high-risk factors as
      they are predictors of relapse. These factors should be recognized by the
      pathologist and should be taken into account by the oncologist when selecting the
      management of a patient with a germ cell tumor of the testis.

PMID- 9649231
TI  - Germ cell tumors: staging, prognosis, and outcome.
AB  - Germ cell tumors (GCT) remain the model for solid tumor therapy. Until 1997, GCT
      staging was based on individual institution systems, which limited comparison of
      data and collaboration between GCT groups. GCT staging is based on four basic
      criteria: disease site of origin, histology, secretion of serum tumor markers
      (STM), and bulk of disease. Within most staging systems developed by
      investigators, clinical stage I disease is confined to the testis based on
      radiographic imaging and STM or pathological stage I based on lack of
      histological disease at retroperitoneal lymphadenectomy. Stages II and III are
      considered to be disease outside the testis categorized by lymphatic spread to
      the retroperitoneal lymph nodes or hematological spread to lungs and visceral
      organs, respectively. The major staging systems previously used include the
      Indiana University Staging System; Modified Samuels' Classification (M.D.
      Anderson Cancer Center); Memorial Sloan Kettering Cancer Center Mathematical
      Model; and the Tumor, Nodal, Metastases (TNM) Staging System (American Joint
      Committee on Cancer). The most recent evolution in staging systems is the 1997
      International Germ Cell Consensus Classification, which is based on prognosis and
      outcomes. This system allows for comparison of data and collaboration between
      Germ Cell Tumor Groups.

PMID- 9649232
TI  - Dose intensity: its limitation and the M. D. Anderson Cancer Center's view of its
      application.
AB  - Therapy for germ cell tumors has been viewed as a model of successful treatment
      development in solid tumors. Despite this, treatment remains unsatisfactory in
      patients with poor risk or high volume at initial presentation. Present
      strategies under investigation include the use of dose intensification through
      the shortening of treatment intervals and the dose escalation of agents with a
      presumed dose-response relationship in the presence or absence of bone marrow
      transplant or stem cell support.

PMID- 9649233
TI  - Heat-related mortality--United States, 1997.
AB  - Environmental heat exposure can cause illness, injury, and death. This report
      describes four heat-related deaths that occurred in the United States during 1997
      and summarizes risk factors for and reviews measures to prevent heat-related
      illness, injury, and death.

PMID- 9649234
TI  - Statewide surveillance for ehrlichiosis--Connecticut and New York, 1994-1997.
AB  - In the United States, human monocytic ehrlichiosis (HME) and human granulocytic
      ehrlichiosis (HGE) represent two clinically indistinguishable yet
      epidemiologically and etiologically distinct diseases caused by Ehrlichia
      chaffeensis and a bacterium similar or identical to E. equi, respectively.
      Infection with these emerging tickborne pathogens results in acute, influenza
      like illnesses with fever, headache, malaise, and frequently leukopenia and/or
      thrombocytopenia. Connecticut and New York have initiated statewide laboratory
      based surveillance to determine the magnitude and geographic extent of
      ehrlichiosis. This report summarizes results from the first 3 years of
      surveillance, which showed that rates of ehrlichiosis were similar in counties in
      both states where the disease occurs, and highest age-specific rates occurred
      among persons aged >40 years.

PMID- 9649235
TI  - Sun-protection behaviors used by adults for their children--United States, 1997.
AB  - In the United States, the high incidence of skin cancer--including basal cell
      carcinoma, squamous cell carcinoma, and melanoma-has been attributed primarily to
      sun exposure. To reduce exposures to the sun's harmful ultraviolet (UV) rays, the
      American Academy of Dermatology (AAD), the American Cancer Society, and other
      organizations have recommended sun-protection practices such as wearing
      protective clothing, avoiding sun exposure during the midday hours (when the
      sun's rays are the strongest), and using sunscreen. Such practices are especially
      important for infants and children because sun exposure during the early years of
      life appears to increase the risk for melanoma, the most serious form of skin
      cancer. To characterize sun-protection practices among children, AAD conducted a
      survey of parents with children aged < or =12 years during June-July 1997. This
      report summarizes the results of the survey, which indicate that three fourths of
      adults had their children use one or more measures to reduce exposure to UV rays.

PMID- 9649236
TI  - Multistate outbreak of hemolysis in hemodialysis patients--Nebraska and Maryland,
      1998.
AB  - From May 13 through May 23, 1998, a total of 30 patients in three states
      developed hemolysis with or without chest pains, shortness of breath, nausea, or
      abdominal pain while undergoing hemodialysis (HD). Two patients died. This report
      summarizes the preliminary findings of investigations in Nebraska and Maryland
      and implicated lot number 04015309 of Cobe Centrysystem 3 Blood Tubing sets
      (Gambro Healthcare, Lakewood, Colorado) as the cause of these reactions.

PMID- 9649237
TI  - Studies on gender differences in beta-adrenergic receptors in rabbit bladder.

PMID- 9649238
TI  - Positron emission tomography in urological oncology.
AB  - PURPOSE: We provide scientists and clinicians with an introduction to the basic
      principles and methods of positron emission tomography (PET) and summarize the
      recent research and clinical applications of PET in the urological field.
      Specifically, we introduce PET so that the reader can understand and objectively
      review current and future articles that involve this imaging technology.
      MATERIALS AND METHODS: The recent applications of PET in urology in the published
      literature were searched and reviewed. RESULTS: In prostate carcinoma preliminary
      studies using radiotracer 18-fluoro-2-deoxyglucose (FDG) demonstrated that PET
      cannot reliably differentiate between primary prostate cancer and benign
      prostatic hyperplasia, and that PET is not as sensitive as bone scintigraphy for
      the detection of osseous metastases. However, PET may have a role in the
      detection of lymph node metastases in patients with prostate specific antigen
      relapse after primary local therapy. In renal cell carcinoma recent studies have
      shown the ability of FDG PET to detect primary and metastatic lesions and to
      monitor response to therapy. In the staging of testicular cancer FDG PET has been
      used to differentiate viable carcinoma from benign teratomas and/or fibrotic or
      necrotic changes. CONCLUSIONS: Current developments in PET technology that
      accurately stage the extent of tumor before surgery as well as monitor
      effectiveness or ineffectiveness of new or current therapies may make PET a
      valuable tool in research and in the management of urological diseases.

PMID- 9649239
TI  - Long-term outcome in patients with pTxN+ adenocarcinoma of prostate treated with
      radical prostatectomy and early androgen ablation.
AB  - PURPOSE: We assessed retrospectively the outcome after bilateral pelvic
      lymphadenectomy and radical prostatectomy for pathological pTxN+ adenocarcinoma
      of the prostate when treated with or without adjuvant androgen ablation therapy.
      MATERIALS AND METHODS: A total of 790 men treated with radical prostatectomy for
      prostatic adenocarcinoma were found to have pTxN+ disease and treated further
      with or without androgen ablation therapy. Mean patient age was 64 years (range
      40 to 79). Mean followup was 6.5 years, (range up to 25). Clinical stages were T2
      or less in 60% of the cases, T3 in 38% and N+ in 2%. Gleason scores were 6 or
      less in 31% and 7 or greater in 69%. Deoxyribonucleic acid ploidy was diploid in
      43%, tetraploid in 39% and aneuploid in 18%. Of the patients 96 (12%) received no
      androgen ablation therapy, with the remainder getting androgen ablation therapy
      within 90 days of radical prostatectomy. RESULTS: Of the patients 186 (24%) died,
      with 109 (14%) dying of prostatic anedocarcinoma. Overall (and cause specific)
      survival probabilities at 5, 10 and 15 years were 87 (91), 69 (79) and 39% (60%),
      respectively. Patients with diploid tumors had better cause specific survival
      than those with nondiploid tumors (p = 0.009). Patients with diploid tumors were
      less likely to have progression biochemically, locally or systemically than those
      with nondiploid tumors (p = 0.038). Androgen ablation therapy had no effect on
      cause specific survival in nondiploid patients. Diploid patients treated with
      androgen ablation therapy for up to 10 years had no improvement in disease
      specific survival compared to those with no androgen ablation therapy. However,
      cancer death was significantly reduced after 10 years (p <0.002). The local
      control rate of pTxN+ cases that receive radical prostatectomy and androgen
      ablation therapy at 15 years is virtually identical to that of stage pT2c cases
      at our institution (79 +/- 3.0 versus 80% +/- 3.5%, respectively). There were no
      deaths secondary to radical prostatectomy, and complications were within the
      experience of that seen in patients with localized disease. CONCLUSIONS: Radical
      prostatectomy with androgen ablation therapy is a viable option for patients with
      pTxN+ disease, particularly in view of excellent local control rates and low
      morbidity. Patients with diploid tumors have a more favorable outcome than those
      with nondiploid tumors when treated with androgen ablation therapy.

PMID- 9649240
TI  - Renal colic during pregnancy: a case for conservative treatment.
AB  - PURPOSE: We defined the merits of early evaluation and conservative treatment of
      pregnant patients admitted with renal colic. MATERIALS AND METHODS: We
      retrospectively evaluated 72 pregnancies in 70 patients who were hospitalized
      with the diagnosis of renal colic between 1984 and 1995. Urinalysis was performed
      in every case. Ultrasound was the primary diagnostic test in 65 patients. The
      patients were followed for 2 weeks to 3 months after delivery (mean 21 days).
      RESULTS: Mean patient age at presentation was 27.4 years. The majority of
      patients were multiparous (47 of 70) and presented in the third trimester (44 of
      70). Microscopic urinalysis was not helpful in identifying stone disease in
      pregnant patients. The sensitivity of ultrasound for the diagnosis of renal
      calculi was 95.2%. Watchful conservative nonsurgical treatment resulted in
      spontaneous passage of stones in 64.3% of cases. Of the 19 pregnancies in which
      intervention was necessary cystoscopy and Double-J* silicone stent placement were
      done in 15, and ureteroscopy and stone basketing were done in 4. Two patients,
      who presented with pyelonephritis and premature ruptured membranes had fetal
      loss. Long-term antibiotic prophylaxis was maintained in all stented and
      bacteriuric patients. CONCLUSIONS: Renal colic in pregnant patients can be
      complicated by pyelonephritis and premature labor, especially if misdiagnosed or
      inadequately treated. Ultrasound is a safe and sensitive diagnostic test.
      Approximately two-thirds of renal calculi will pass spontaneously. For those who
      require intervention, placement of a Double-J stent is a safe and effective
      option.

PMID- 9649241
TI  - Predictors of outcome in emphysematous pyelonephritis.
AB  - PURPOSE: We identified and quantified prognostic factors for emphysematous
      pyelonephritis. MATERIALS AND METHODS: The clinical information, laboratory data
      and radiological findings from 38 patients with emphysematous pyelonephritis were
      retrospectively analyzed. RESULTS: There were no significant differences between
      the nonsurvivor and survivor groups with respect to age, gender, diabetes
      mellitus history, presence of bacteremia, identity of infecting organisms, blood
      glucose level, leukocyte count, urinary white blood count, presence or absence of
      urinary tract obstruction or urolithiasis, and modes of treatment. There were
      significant differences between the nonsurvivor and survivor groups, however,
      with respect to platelet count (84,300 +/- 119,500 versus 220,400 +/-
      161,800/mm.3, p = 0.001), serum creatinine level (3.61 +/- 1.25 versus 2.19 +/-
      1.32 mg./dl., p = 0.003) and urinary red blood counts (56.47 +/- 41.86 versus
      27.65 +/- 36.14, p = 0.028). Patients with radiological type I emphysematous
      pyelonephritis were significantly more likely to die than those with type II (69
      versus 18%, p = 0.002). CONCLUSIONS: Serum creatinine level is the most reliable
      predictor of outcome in patients with emphysematous pyelonephritis. By
      calculating likelihood ratios, patients with creatinine levels greater than 1.4
      mg./dl. and platelet counts 60,000/mm.3 or less were at high risk. The posttest
      probability of death increased from 69 and 18% to 92 and 53% for type I and II
      emphysematous pyelonephritis, respectively. Patients with creatinine levels 1.4
      mg./dl. or less and platelet counts greater than 60,000/mm.3 were at much lower
      risk. Posttest mortality risk in these patients dropped from 69 and 18% to 27 and
      4% for type I and II emphysematous pyelonephritis, respectively.

PMID- 9649242
TI  - Current indications for open stone surgery in the treatment of renal and ureteral
      calculi.
AB  - PURPOSE: The development and advances in extracorporeal shock wave lithotripsy
      and endourological procedures have greatly diminished the need for open surgery
      in the treatment of renal and ureteral stones. We reviewed our experience with
      open stone surgery to determine the current indications and efficacy of this
      treatment modality. MATERIALS AND METHODS: Hospital and office charts, operative
      notes and records, and pertinent radiographic studies of all patients undergoing
      open stone surgery from January 1991 through December 1995 at 3 university
      affiliated hospitals were reviewed. Patient characteristics, stone burden,
      indications, surgical factors and outcomes were reviewed for each patient.
      RESULTS: Of 780 procedures performed for stone removal, 42 were open surgical
      procedures (5.4%) including pyelolithotomy in 15 (extended pyelolithotomy or
      pyelonephrolithotomy in 7), anatrophic nephrolithotomy in 14, ureterolithotomy in
      7 and radial nephrolithotomy in 6. There were 24 men and 18 women ranging in age
      from 1 to 90 years (mean age 51.5). The most common indications for open surgery
      were complex stone burden (55%); failure of extracorporeal shock wave lithotripsy
      or endourological treatment (29%); anatomic abnormalities such as ureteropelvic
      junction obstruction, infundibular stenosis and/or renal caliceal diverticulum
      (24%); morbid obesity (10%) and co-morbid medical disease (7%). Mean estimated
      blood loss was 428 cc. Average hospital stay was 6.4 days. The stone-free rate
      after surgery was 93%. Five patients had minor postoperative complications that
      resolved with appropriate therapy. CONCLUSIONS: While most patients with renal
      and ureteral stones can be treated with less invasive techniques, open stone
      surgery continues to represent a reasonable alternative for a small segment of
      the urinary stone population.

PMID- 9649243
TI  - Relationship between glutathione S-transferase M1 deficiency and urothelial
      cancer in dye workers exposed to aromatic amines.
AB  - PURPOSE: It is speculated that the susceptibility to urothelial cancer in dye
      workers who are exposed to aromatic amines is affected not only by occupational
      environmental factors but by host specific factors. We evaluated the interaction
      between glutathione S-transferase M1 gene deficiency and the occupational
      environmental factors associated with urothelial cancer. MATERIALS AND METHODS:
      The study included 137 workers who had prior exposure to dyestuff intermediates,
      of whom 36 had urothelial cancer. The prevalence of a glutathione S-transferase
      M1 gene polymorphism was investigated using polymerase chain reaction. The
      relationship between the glutathione S-transferase M1 0/0 gene and occupational
      environmental factors in the onset of urothelial cancer was examined by
      multivariate analysis. RESULTS: The prevalence of glutathione S-transferase M1
      gene deficiency did not differ significantly between the urothelial cancer (21
      cases, 58.3%) group and the cancer-free (47, 46.3%) group. It was estimated that
      29.6% of the urothelial cancers in these dye workers was attributable to the
      glutathione S-transferase M1 0/0 gene. Analysis using multiple logistic models
      showed low predictive ability for urothelial cancer due to glutathione S
      transferase M1 gene deficiency (p = 0.084, odds ratio 2.260, 95% confidence
      interval [CI] 0.904 to 5.652). A history of working in small factories (p =
      0.000, odds ratio 7.404, 95% CI 2.854 to 19.206) and a long period of exposure (p
      = 0.016, odds ratio 5.051, 95% CI 1.371 to 18.612) significantly predicted
      cancer. CONCLUSIONS: We demonstrated a strong trend using the multiple logistic
      analysis of the contribution of glutathione S-transferase M1 gene polymorphism
      and occupational environmental factors. Therefore, the glutathione S-transferase
      M1 enzyme might have an important role in the detoxification of aromatic amine
      derived carcinogens. Occupational environmental factors, however, might
      contribute more than a glutathione S-transferase M1 gene deficiency to the
      occurrence of urothelial cancer among individuals exposed to aromatic amines,
      because of the extremely potent carcinogenicity of some occupational
      environmental factors.

PMID- 9649244
TI  - Use of Lewis X antigen and deoxyribonucleic acid image cytometry to increase
      sensitivity of urinary cytology in transitional cell carcinoma of the bladder.
AB  - PURPOSE: To improve sensitivity and specificity of urinary cytology for bladder
      cancer cell detection we used deoxyribonucleic acid (DNA) image cytometry and the
      monoclonal anti-Lewis X antibody P12. MATERIALS AND METHODS: Spontaneously voided
      urine and additional barbotage bladder washings of 25 patients with transitional
      cell carcinomas and 25 patients with benign diseases of the bladder were analyzed
      by conventional cytology, immunocytology and DNA image cytometry. The DNA content
      was determined in specimens stained with Feulgen according to the European
      Society for Analytical Cellular Pathology consensus report on standardization of
      DNA image cytometry. For the immunocytological examination we used the avidin
      biotin-complex immunoperoxidase method with the monoclonal antibody P12 directed
      against the Lewis X determinant. RESULTS: The cytological examination revealed a
      sensitivity of 72% and a specificity of 100%. By using DNA image cytometry with
      Kolmogoroff-Smirnow test sensitivity increased up to 84% with a specificity of
      100%. The immunocytological examination with Lewis X showed a sensitivity of 84%
      and a specificity of 80%. CONCLUSIONS: Combining cytology and DNA cytometry the
      overall sensitivity increased to 92% and with the additional application of
      immunocytology for Lewis X antigen sensitivity it increased to 96% but was
      accompanied by a decrease in specificity to 80%. DNA image cytometry and Lewis X
      antigen detection are not suitable for screening but suspicious urothelial cells
      in urinary cytology specimens can be evaluated specifically by DNA measurements.
      In the future it needs to be clarified whether DNA image cytometry in combination
      with Lewis X antigen detection can help to signal relapse and progression of
      transitional cell carcinoma of the bladder.

PMID- 9649245
TI  - Immunostaining of Lewis X in cells from voided urine, cytopathology and
      ultrasound for noninvasive detection of bladder tumors.
AB  - PURPOSE: We examined the use of immunostaining of the Lewis X antigen in
      exfoliated cells from voided urine samples, cytopathology and bladder ultrasound
      for noninvasive detection of bladder tumors as a potential substitute for
      cystoscopy. MATERIALS AND METHODS: A total of 260 patients were included, of whom
      80 were evaluated because of irritative symptoms or hematuria and 180 were
      examined during followup visits after resection of bladder tumors. Voided urine
      samples were obtained from each patient for immunocytology and cytopathology.
      Bladder ultrasound and cystoscopy were performed. Biopsies were obtained whenever
      a bladder tumor was seen or if carcinoma in situ was suspected. Indirect
      immunoperoxidase staining was done on cytocentrifuge slides, using the P12
      monoclonal antibody against the Lewis X antigen. RESULTS: Cystoscopy and biopsies
      revealed bladder tumors in 84 patients. Immunocytology of 1 urine sample resulted
      in a sensitivity of 79.8% and a specificity of 86.4%. The diagnosis of primary
      carcinoma in situ by immunocytology was correct in 100% of the cases. The
      examination of 2 consecutive urine samples detected 95.1% of the tumors. False
      negative results occurred in a few cases with small, superficial, low grade
      tumors. Cytopathology and bladder ultrasound resulted in a sensitivity of 47.6
      and 66.7%, and a specificity of 97.7 and 97.2%, respectively. The results of
      immunocytology of 2 urine samples were equivalent to the combination of
      immunocytology of a single urine sample, cytology and ultrasound. CONCLUSIONS:
      Immunostaining of the Lewis X antigen is significantly more sensitive than
      cytopathology for the detection of low grade as well as high grade tumor cells in
      voided urine. Immunocytological evaluation of 2 consecutive voided urine
      specimens for the Lewis X antigen is the most sensitive method currently
      available for noninvasive detection of transitional cell tumors. This assay may
      replace cystoscopy for detection of bladder cancer.

PMID- 9649246
TI  - Evaluation of NMP22 in the detection of transitional cell carcinoma of the
      bladder.
AB  - PURPOSE: Urinary nuclear matrix protein (NMP22) was evaluated for detection of
      new and recurrent bladder tumors in patients with a history of transitional cell
      carcinoma. Our objective was to determine sensitivity and specificity of this
      marker for tumors of various stages and grades, as well as its use as an adjunct
      to or substitute for urinary cytology. MATERIALS AND METHODS: A total of 231
      patients with a history of transitional cell carcinoma provided 288 voided urine
      samples before cystoscopic examination at 1 of 3 institutions (53 patients were
      reevaluated at least once). Urine samples were assayed for NMP22 using the NMP22
      Test Kit. Select patients underwent biopsy with appropriate additional therapy.
      Voided urinary cytology was obtained in 200 cases. End points for determination
      of the absence and presence of tumor were negative cystoscopy and positive
      biopsy, respectively. A receiver operating characteristics curve was constructed
      to determine the optimal NMP22 threshold for detection of transitional cell
      carcinoma. For positive biopsies NMP22 values were also correlated with tumor
      stage and grade. Comparison to cytology was limited to patients with complete
      data. RESULTS: There were 208 negative cystoscopies (158 with cytology) and 66
      positive cystoscopies with biopsy (42 with cytology). Of the cases 14 were
      eliminated from statistical analysis due to incomplete data. Receiver operating
      characteristics curve interpretation determined that 6.4 units per ml. was an
      optimal reference value for detection of transitional cell carcinoma in this
      patient group. Sensitivity and specificity for all pathological groupings was 68
      and 80%, respectively. When compared to cytology the sensitivities of NMP22 and
      cytology were 67 versus 31 or 40% (depending on the definition of positive
      cytology). CONCLUSIONS: NMP22 values represented significant improvement over
      urinary cytology for detection of transitional cell carcinoma. The sensitivity of
      NMP22 for detection of transitional cell carcinoma in bladder cancer patients was
      as much as twice that of cytology when a reference value of 6.4 units per ml. was
      used. NMP22 analysis was less costly than cytology and operator independent.
      While NMP22 has previously been shown to be a strong predictor of recurrence
      after tumor resection, it is an effective and sensitive screening test for
      detecting tumors in patients with transitional cell carcinoma.

PMID- 9649247
TI  - Is the role of cystoscopy in the detection of bladder cancer really declining?

PMID- 9649248
TI  - Early clinical experience with 5-aminolevulinic acid for the photodynamic therapy
      of upper tract urothelial tumors.
AB  - PURPOSE: Photodynamic therapy is effective in the treatment of superficial
      urothelial cancer of the bladder. We report our experience with photodynamic
      therapy for the treatment of upper urinary tract transitional cell carcinoma.
      MATERIALS AND METHODS: Photodynamic therapy after oral administration of 5
      aminolevulinic acid was performed in 4 patients with widespread superficial
      papillary tumors of the upper urinary tract. RESULTS: Complete remission occurred
      in 2 patients who remained free of local recurrence at 7 and 17 months of
      followup. In the other 2 patients residual tiny papillary tumors were found in
      the distal ureter after photodynamic therapy. These tumors were coagulated with
      neodymium:YAG laser irradiation. Both patients are disease-free at 24-month
      followup. CONCLUSIONS: Photodynamic therapy with 5-aminolevulinic acid is a
      minimally invasive approach for organ preserving treatment of multifocal
      superficial transitional cell carcinoma of the upper urinary tract.

PMID- 9649249
TI  - Detection of Mycoplasma genitalium in patients with urethritis.
AB  - PURPOSE: We attempted to detect Mycoplasma genitalium in urethral swab specimens
      by a polymerase chain reaction based assay to determine the prevalence of M.
      genitalium in patients with urethritis. MATERIALS AND METHODS: We examined a
      total of 171 Japanese men who presented to our hospital from February 1995
      through January 1997. Of these men 150 had symptoms and signs compatible with
      acute urethritis and 21 had no symptoms or signs of urethritis. Urethral swab
      specimens were used to culture Neisseria gonorrhoeae, to detect Chlamydia
      trachomatis by an enzyme immunoassay and to detect M. genitalium by a polymerase
      chain reaction based assay. RESULTS: Gonococcal urethritis was diagnosed in 74
      symptomatic men, and nongonococcal urethritis was diagnosed in 76 symptomatic
      men. Of the 74 cases of gonococcal urethritis 3 (4.1%) were positive for M.
      genitalium, and 14 (18.9%) were positive for C. trachomatis. Of the 76 cases of
      nongonococcal urethritis 10 (13.2%) were positive for M. genitalium, and 42
      (55.2%) were positive for C. trachomatis. While only 1 of the 42 cases with
      chlamydial nongonococcal urethritis (2.4%) was positive for M. genitalium, 9 of
      the 34 chlamydia negative nongonococcal urethritis cases (26.5%) were positive
      for the mycoplasma. In contrast, all 21 cases men were negative for N.
      gonorrhoeae, M. genitalium, and C. trachomatis. CONCLUSIONS: The prevalences of
      M. genitalium in patients with gonococcal urethritis and nongonococcal urethritis
      who attended our clinic were 4.1 and 13.2%, respectively. M. genitalium was
      detected significantly more often in men with nongonococcal urethritis than in
      asymptomatic men. In addition, its prevalence in men with chlamydia negative
      nongonococcal urethritis (26.5%) was significantly greater than in those with
      chlamydia positive nongonococcal urethritis (2.4%). These findings suggest that
      M. genitalium may be associated with the development of nongonococcal urethritis
      independent of C. trachomatis.

PMID- 9649250
TI  - Detection of urethral diverticula in women: comparison of a high resolution fast
      spin echo technique with double balloon urethrography.
AB  - PURPOSE: We compared a rapid high resolution magnetic resonance imaging (MRI)
      technique to contrast urethrography for the detection of urethral diverticula in
      women. MATERIALS AND METHODS: During a 19-month interval 13 patients with
      clinically suspected urethral diverticula were evaluated with MRI and contrast
      urethrography. All patients were referred by a urologist, and had clinical signs
      and symptoms suggesting the presence of a urethral diverticulum. Double balloon
      urethrography was performed in 12 patients and voiding cystourethrography was
      done in 1. MRI was performed using a fast spin echo T2-weighted pulse sequence
      and a dedicated pelvic multicoil. Following a sagittal localizer sequence 3 mm.
      thick axial sections were obtained from the bladder base through the entire
      urethra. Total imaging time was 15 minutes. RESULTS: In 7 patients MRI and
      urethrography were negative for urethral diverticula, and in 3 cystourethroscopy
      was negative. In 1 patient MRI revealed a vaginal inclusion cyst confirmed by
      surgery. Three patients had no other studies or procedures performed. In 6
      patients MRI was positive for urethral diverticula, including 4 in whom the
      diverticulum was confirmed at surgery, 1 who declined surgery and 1 who was lost
      to followup. Of the 4 patients (75%) with a surgically confirmed diverticulum
      double balloon urethrogram was negative in 3. CONCLUSIONS: MRI is a valuable
      noninvasive technique for determining the presence of urethral diverticula as
      well as detecting other abnormalities. In our study MRI had a higher sensitivity
      for detecting diverticula and a much higher negative predictive rate.

PMID- 9649251
TI  - Periurethral fat injection in the treatment of recurrent genuine stress
      incontinence.
AB  - PURPOSE: We evaluated the efficacy, safety and mechanism of periurethral fat
      injection in the treatment of recurrent genuine stress incontinence. MATERIALS
      AND METHODS: Periurethral fat injections were performed in 26 patients for the
      treatment of recurrent genuine stress incontinence. A complete urogynecological
      study, including a 1-hour pad test, urodynamic studies and chain
      urethrocystography were done in each case and were repeated at least 3 months
      after operation. Each patient was followed for at least 12 months. RESULTS: Of 26
      patients 13 (50%) were dry after operation and 4 (15.4%) showed improvement and
      were satisfied with the results of the operation, giving a total success rate of
      65.4%. There were 6 cases of immediate postoperative minor complications (23%).
      Average volume of injected fat was 14.8 +/- 4.8 cc, which did not affect the
      success rate. Preoperative and postoperative chain urethrocystographic values for
      bladder neck descent in reference to the pubosacral tip line showed no
      statistical difference between successfully and unsuccessfully treated groups.
      Urodynamic studies in all cases showed no differences relating to operation.
      However, minimal urethral resistance increased from 0.122 +/- 0.061 to 0.205 +/-
      0.134 (p = 0.023) in the treatment success group. This change was not
      demonstrated in the treatment failure group. CONCLUSIONS: Periurethral fat
      injection for the treatment of recurrent genuine stress incontinence is a simple
      technique that works by the increment of urethral resistance. It has an
      acceptable success rate without financial outlay for the injected material.

PMID- 9649252
TI  - Intralesional sclerotherapy in the management of hemangiomas of the glans penis.
AB  - PURPOSE: We studied the role of sclerotherapy in the management of glans penis
      hemangiomas. MATERIALS AND METHODS: Four patients with hemangiomas of the glans
      penis were treated on an outpatient basis with intralesional injections of 30%
      hypertonic saline. RESULTS: In all 4 patients the lesions regressed and all were
      satisfied with the outcome. CONCLUSIONS: Intralesional sclerotherapy is a cost
      effective modality for the treatment of glans penis hemangiomas, especially in
      developing countries and at peripheral hospitals where expensive laser equipment
      may not be available.

PMID- 9649253
TI  - Burns to the genitalia and the perineum.
AB  - PURPOSE: We conducted a study to determine the treatment of perineal and genital
      burns, the results of therapy and the complications of such burns. MATERIALS AND
      METHODS: A review of the records of 4,216 patients treated between 1981 and 1995
      at the Burn Center of the Academic Surgical Center Stuivenberg, revealed 87 male
      and 30 female patients, 6 months to 86 years old who had associated burns to the
      perineum or genitalia. Mean burn size was 21% of the total body surface area.
      Causes of burn injury were scald in 55% of the cases, flame in 24%, chemical in
      16% and others in 4%. RESULTS: There were 16 deaths in this group (13.6%) but
      none was related to the perineal or genital burns. Of the 101 survivors 41%
      required Foley catheters but the catheters were indwelling during resuscitation
      only (range 1 to 99 days). Perineal and genital burns were treated by topical
      antimicrobials. Only 10 patients (9.9%) required split-thickness skin grafts. As
      late complication 2 patients had scar formation of the penile shaft, which was
      treated with multiple Z-plasties, and of the prepuce, which was treated by
      circumcision, respectively. In 1 patient, who presented with erectile dysfunction
      diagnostic evaluation was negative. CONCLUSIONS: Conservative management of
      perineal and genital burns is recommended.

PMID- 9649254
TI  - Management of the buried penis in adults.
AB  - PURPOSE: Buried penis, most commonly seen in children, is particularly
      debilitating in adults, resulting in the inability to void standing and it
      affects vaginal penetration. The pathophysiology, including scar contracture of
      the distal soft tissue and skin envelope with concurrent descent of the abdominal
      fat pad, represents a surgical challenge. We developed a management algorithm to
      evaluate and treat adults with buried penis. MATERIALS AND METHODS: From January
      1, 1994 to May 1, 1996, 7 patients 23 to 66 years old presented with buried
      penis. Diabetes mellitus, a common co-morbid condition, was present in 5
      patients, and 5 of 7 were morbidly obese. RESULTS: Surgical correction was
      performed in 5 patients with excellent results in 3. Resection of scar
      contracture was sufficient to provide adequate length and none required release
      of the suspensory ligament. Panniculectomy was performed in 1 patient. One man
      requiring a graft to achieve adequate penile coverage required reoperation. This
      patient had undergone a previous attempted repair with extensive contracture. All
      patients regained potency postoperatively. CONCLUSIONS: With appropriate planning
      and adherence to basic reconstructive surgical principles, correction of the
      buried penis can yield a high success rate.

PMID- 9649255
TI  - Efficacy and safety of fluoxetine, sertraline and clomipramine in patients with
      premature ejaculation: a double-blind, placebo controlled study.
AB  - PURPOSE: We compared the efficacy and safety of fluoxetine, sertraline,
      clomipramine and placebo for the oral pharmacotherapy of premature ejaculation.
      MATERIALS AND METHODS: The study included 36 men (mean age 44 years) who had
      intravaginal ejaculation latency of less than 2 minutes. Patients took each of 3
      drugs and the placebo consecutively during a 4-week period per each agent.
      Efficacy and side effects data were obtained by a self-reported patient
      questionnaire that rated intravaginal ejaculation latency, sexual satisfaction of
      patient and partner, and possible side effects. RESULTS: After 4 weeks of
      treatment with placebo, fluoxetine, sertraline and clomipramine the mean
      intravaginal ejaculation latency time was significantly increased from 46 seconds
      to 2.27 minutes, 2.30 minutes, 4.27 minutes and 5.75 minutes, respectively (all p
      <0.01). However, treatment with clomipramine or sertraline caused a greater
      increase in mean intravaginal ejaculation latency time than fluoxetine or placebo
      (p <0.01). Patient sexual satisfaction rate after treatment with clomipramine was
      significantly higher (p <0.05) than with sertraline, fluoxetine or placebo.
      Partner sexual satisfaction rate was also higher with clomipramine than with
      sertraline or fluoxetine but no statistical difference was found. The incidence
      of side effects with clomipramine was significantly higher (p <0.05) compared to
      that of fluoxetine, sertraline and placebo, while no significant difference among
      sertraline, fluoxetine and placebo was noted. CONCLUSIONS: In men with premature
      ejaculation clomipramine was the most useful drug in terms of efficacy. Treatment
      with sertraline was nearly as effective and had a lower incidence of side
      effects.

PMID- 9649256
TI  - Cavernous arterial and arteriolar circulation in patients with erectile
      dysfunction: a power Doppler study.
AB  - PURPOSE: We assessed the morphodynamic features of cavernous arteries and
      helicine arterioles by power Doppler sonography in vasculogenic and
      nonvasculogenic impotent men. MATERIALS AND METHODS: A total of 40 impotent
      patients with and without definite vascular risk factors were studied by penile
      power Doppler sonography. The test was performed during penile flaccidity, after
      intracavernous injection of 20 mcg. alprostadil and after subsequent genital and
      audiovisual sexual stimulation. A second injection and stimulation were given if
      the erectile response observed after the initial injection was less than the
      maximum erection seen during sexual activity. Morphodynamic parameters evaluated
      by power Doppler imaging included vessel course, shape, wall thickness and
      pulsatility, peak systolic velocity, end diastolic velocity, acceleration time
      and resistance index. RESULTS: In the nonvasculogenic group all patients who
      achieved rigid erection showed normal cavernosal artery and helicine arteriole
      inflow. In these cases the arteriolar picture was characterized by the presence
      of 3 orders of distal ramifications originating from the cavernous arteries with
      an acute angle, systolic diastolic flow during penile tumescence and systolic
      flow alone at full rigidity. In the vasculogenic group patients with normal
      cavernous artery inflow showed an arteriolar tree that was pathological in 50%
      and was characterized by a reduced number of ramifications originating
      perpendicularly from the cavernous arteries and irregular caliber (arteriolar
      impotence). In the same group patients with reduced cavernous artery inflow also
      showed normal or pathological arteriolar components (pre-penile arterial
      impotence and diffused penile arterial impotence). CONCLUSIONS: Power Doppler
      sonography allows a precise study of the morphodynamics of the cavernous arteries
      and helicine arterioles. Our preliminary data suggest that the intracavernous
      arteriolar component may have a significant role in the genesis of some forms of
      vasculogenic impotence.

PMID- 9649257
TI  - Yohimbine for erectile dysfunction: a systematic review and meta-analysis of
      randomized clinical trials.
AB  - PURPOSE: Erectile dysfunction is a common problem, particularly in diabetics. It
      is associated with a considerable burden of suffering. No generally accepted drug
      treatment exists. We systematically reviewed and meta-analyzed all randomized,
      placebo controlled trials of yohimbine monotherapy for erectile dysfunction to
      determine its therapeutic efficacy. Our secondary aim was to evaluate the safety
      of yohimbine. MATERIALS AND METHODS: We used computerized literature searches and
      standardized data extraction to rate methodological quality in a meta-analysis
      using computer statistical software. RESULTS: Seven trials fit the predefined
      inclusion criteria. Overall methodological quality of these studies was
      satisfactory. The meta-analysis demonstrated that yohimbine is superior to
      placebo in the treatment of erectile dysfunction (odds ratio 3.85, 95% confidence
      interval 6.67 to 2.22). Serious adverse reactions were infrequent and reversible.
      CONCLUSIONS: The benefit of yohimbine medication for erectile dysfunction seems
      to outweigh its risks. Therefore, yohimbine is believed to be a reasonable
      therapeutic option for erectile dysfunction that should be considered as initial
      pharmacological intervention.

PMID- 9649258
TI  - Successful sperm retrieval by percutaneous epididymal and testicular sperm
      aspiration.
AB  - PURPOSE: We evaluated the safety and efficacy of percutaneous sperm aspiration
      from the epididymis or testicle as a diagnostic technique to confirm sperm
      production and as a therapeutic technique to harvest sperm for use in
      intracytoplasmic sperm injection. MATERIALS AND METHODS: We present our
      experience with 69 sperm aspiration procedures in men considered to have
      nonreconstructible obstructive azoospermia. This short outpatient procedure was
      performed using a butterfly needle with the patient under intravenous sedation
      and local anesthesia. RESULTS: Of the 32 diagnostic aspirations 20 demonstrated
      mature and motile sperm, 9 maturation arrest and 3 germ cell aplasia. In 35 of 37
      therapeutic sperm aspirations (95%) adequate samples of sperm after processing
      (mean of 5.4 million) were obtained. Of 24 epididymal aspirations 13 (54%) had
      sufficient residual sperm for cryopreservation of 1 to 5 vials (mean 2.5)
      containing an average of 170,000 sperm per vial. In the 32 intracytoplasmic sperm
      injection cycles 221 of 392 eggs (56.3%) fertilized (2PN) and 6 resulted in
      ongoing pregnancies (21.4% per transfer). There have been no acute or chronic
      complications in this patient population. Ten men underwent a second successful
      aspiration procedure for intracytoplasmic sperm injection and 3 underwent a third
      aspiration without added difficulty. CONCLUSIONS: Percutaneous epididymal or
      testis sperm aspiration is a minimally invasive sperm retrieval technique and
      appears to be an effective alternative to microsurgical epididymal sperm
      aspiration, which is more invasive, costly and technically difficult.

PMID- 9649259
TI  - Effect of exogenous testosterone on prostate volume, serum and semen prostate
      specific antigen levels in healthy young men.
AB  - PURPOSE: We investigate and define the effects of exogenous testosterone on the
      normal prostate. MATERIALS AND METHODS: A total of 31 healthy volunteers 21 to 39
      years old were randomized to receive either 100, 250 or 500 mg. testosterone via
      intramuscular injection once a week for 15 weeks. Baseline measurements of serum
      testosterone, free testosterone and prostate specific antigen (PSA) were taken at
      week 1. Semen samples were also collected for PSA content and prostate volumes
      were determined by transrectal ultrasound before testosterone injection. Blood
      was then drawn every other week before each testosterone injection for the 15
      weeks, every other week thereafter until week 28 and again at week 40. After the
      first 15 weeks semen samples were again collected, and prostate volumes were
      determined by repeat transrectal ultrasound. RESULTS: Free and total serum
      testosterone levels increased significantly in the 250 and 500 mg. dose groups.
      No significant change occurred in the prostate volume or serum PSA levels at any
      dose of exogenous testosterone. Total semen PSA levels decreased following
      administration of testosterone but did not reach statistical significance.
      CONCLUSIONS: Despite significant elevations in serum total and free testosterone,
      healthy young men do not demonstrate increased serum or semen PSA levels, or
      increased prostate volume in response to exogenous testosterone injections.

PMID- 9649260
TI  - Age specific prostate specific antigen reference ranges: population specific.
AB  - PURPOSE: We determined whether 60 to 79-year-old men with a negative digital
      rectal examination and a serum prostate specific antigen (PSA) within age
      specific PSA reference ranges could safely forgo prostate biopsy. MATERIALS AND
      METHODS: We reviewed the medical records of all 60 to 79-year-old men at the
      Brooklyn Veterans Administration Medical Center who had a PSA assay, digital
      rectal examination and subsequent prostate biopsy for an abnormal rectal
      examination and/or PSA greater than 4.0 ng./ml. from January 1991 through August
      1995. We compared our results using the standard reference range of 0 to 4.0
      ng./ml. with those obtained had we used any of 4 different age specific PSA
      reference ranges. RESULTS: We performed 1,280 prostate biopsies in 1,046 men with
      available PSA and digital rectal examination data. Using age specific PSA
      reference ranges 73 of 1,280 biopsies (5.7%) would have been avoided. Of those 73
      avoided biopsies 15 (20.5%) had cancer that would have gone undetected and 9 of
      15 (60%) undetected cancers had unfavorable histology. Results were not
      statistically significantly different among the 4 age specific PSA reference
      ranges. Regarding race, cancer detection rates were significantly higher for
      black compared with white men but there was no statistically significant
      difference for missed cancers or missed cancers with unfavorable histology.
      CONCLUSIONS: In contrast to previous reports of unfavorable histological
      characteristics in only 5% of missed cancers using age specific PSA reference
      ranges, 60% of missed cancers in our patients exhibited unfavorable histology. We
      conclude that age specific PSA reference ranges did not safely eliminate the need
      for prostate biopsy in our study population. In 60 to 79-year-old men with a
      negative digital rectal examination we continue to use PSA greater than 4.0
      ng./ml. as an indication for prostate biopsy.

PMID- 9649261
TI  - Influence of finasteride on free and total serum prostate specific antigen levels
      in men with benign prostatic hyperplasia.
AB  - PURPOSE: Finasteride therapy for benign prostatic hyperplasia (BPH) results in a
      marked lowering of serum prostate specific antigen (PSA) levels. However, little
      is known about the effect of finasteride on unbound or free serum levels of PSA.
      Such information would be important since percent free PSA may substantially
      improve the cancer specificity of PSA testing. Thus, we prospectively studied the
      effect of finasteride therapy on total and free serum PSA levels. MATERIALS AND
      METHODS: In a randomized, placebo controlled, double-blind trial 40 men with
      histologically confirmed BPH (age range 52 to 78 years) were treated with either
      5 mg. finasteride daily (26 patients) for 9 months or placebo (14) for 6 months.
      Prostate volume was assessed by transrectal ultrasound. Serum levels of free and
      total PSA were measured from archived serum samples stored at -70C at baseline
      and for as long as 9 months of treatment. RESULTS: In the finasteride group mean
      total PSA levels declined from 3.0 ng./ml. at baseline to 1.5 ng./ml. after 6
      months of treatment (50% decrease, p <0.01). In the placebo group, with similar
      baseline levels, no significant change was observed. PSA density declined
      significantly in finasteride treated men (p <0.01) but not in men receiving
      placebo. The mean percent free PSA (13 to 17% at baseline) was not altered
      significantly by finasteride or placebo. CONCLUSIONS: Total PSA serum levels
      decreased by an average of 50% during finasteride therapy but percent free PSA
      did not change significantly. This information is potentially useful in the
      interpretation of PSA data used for early detection of prostate cancer in men
      receiving finasteride. However, further studies are required to demonstrate the
      use of percent free PSA to detect the development of cancer.

PMID- 9649262
TI  - Transurethral resection of the prostate versus transurethral electrovaporization
      of the prostate: a blinded, prospective comparative study with 1-year followup.
AB  - PURPOSE: Transurethral electrovaporization of the prostate has been increasingly
      used as a surgical adjunct in the management of men with lower urinary tract
      symptoms. In this prospective study we compare the safety and efficacy of
      transurethral resection of the prostate and electrovaporization. MATERIALS AND
      METHODS: We compared 32 consecutive men (mean age 68.9 years) with lower urinary
      tract symptoms treated by transurethral electrovaporization of the prostate to a
      cohort of 32 men (mean age 72.8 years) treated by transurethral resection of the
      prostate. Parameters of evaluation included American Urological Association
      symptom score, peak urinary flow rate, adverse events, including serial changes
      in serum hematocrit and sodium, operative time, postoperative catheterization
      time, hospitalization time and days lost from work. The data were analyzed by an
      investigator who was blinded to which procedure was performed. RESULTS: A total
      of 61 patients were evaluable for followup at 1 year. None required retreatment.
      At 1 year symptom score decreased 12.8 (66% of patients) and 12.2 (67%) and peak
      urinary flow increased 9.7 ml. per second (135%) and 11.3 ml. per second (136%)
      for electrovaporization and resection, respectively, (p <0.001). Operative time
      was significantly longer with electrovaporization than with resection (47.6 +/-
      17.6 versus 34.6 +/- 11.2 minutes, p <0.003). Catheterization time (67.4 +/- 13.6
      versus 12.9 +/- 4.6 hours), hospitalization time (2.6 +/- 0.9 versus 1.3 +/- 0.5
      days) and days lost from work (18.4 +/- 7.6 versus 6.7 +/- 2.1) were
      significantly greater for resection than electrovaporization, respectively. There
      were no major complications in the electrovaporization group while in the
      resection group 1 patient required transfusion (5 units) and in 1 a clinical
      transurethral resection syndrome developed. Potency and retrograde ejaculation
      were normal in 18 of 18 patients (100%) and 13 of 17 (76%) after resection and 19
      of 20 (95%) and 17 of 20 (85%) after electrovaporization. CONCLUSIONS: The
      results indicate that transurethral resection and transurethral
      electrovaporization of the prostate are effective in reducing lower urinary tract
      symptoms with similar preservation of sexual function. Both significantly improve
      peak urinary flow, although resection to a greater degree. Postoperative
      morbidity, catheterization time, hospitalization time and days lost from work
      were significantly less, and operative time was significantly longer with
      electrovaporization. Further studies are underway to determine the long-term
      durability of response of transurethral electrovaporization of the prostate
      relative to transurethral resection.

PMID- 9649263
TI  - Transurethral microwave thermotherapy for benign prostatic hyperplasia: clinical
      outcome after 4 years.
AB  - PURPOSE: We describe long-term results of transurethral microwave thermotherapy.
      We determined pretreatment variables favorable for the outcome. MATERIALS AND
      METHODS: We followed for 4 years 187 patients treated with Prostatron software
      2.0.* Preoperative evaluations consisted of score, cystoscopy, transrectal
      ultrasonography, urine flow and residual volume measurements. Followup
      examinations with score and urodynamics were performed for 4 years after
      transurethral microwave thermotherapy. Kaplan-Meier plots and logistic regression
      were used for statistical analyses. RESULTS: A decrease in the number of
      satisfied patients was noted from 62% at 1 year after transurethral microwave
      thermotherapy to 23% at 4 years. Initial decrease in score and increase in urine
      flow were followed by increase in score and decrease in flow at the 4-year
      followup of the 56 patients who had not received supplementary benign prostatic
      hyperplasia (BPH) treatment. The Kaplan-Meier analysis estimated the median time
      for need of supplementary BPH treatment to be 45 months. Pretreatment urine flow
      greater than 10 ml. per second and an irritative score less than 5 were the only
      factors related to a favorable outcome. Prostate volume or energy delivered to
      the prostate did not influence the result. CONCLUSIONS: Four years after
      transurethral microwave thermotherapy 23% of the initially treated group were
      satisfied with the result. Two-thirds had received supplementary BPH treatment.
      Preoperatively less obstructed patients and those with low initial irritative
      scores responded more favorably to transurethral microwave thermotherapy
      treatment.

PMID- 9649264
TI  - Endothelial cell proliferation activity in benign prostatic hyperplasia and
      prostate cancer: an in vitro model for assessment.
AB  - PURPOSE: Urinary excretion of several pro-angiogenic and antiangiogenic
      substances has been correlated with malignant tumor growth. The aim of this study
      was to assay angiogenic activity in urine from patients with cancer of the
      prostate and benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Urine
      specimens from 22 healthy male volunteers (control), 33 patients with BPH and 29
      with organ confined prostate cancer were analyzed for angiogenic activity in a
      bovine capillary endothelial cell proliferation assay. In parallel the
      concentration of basic fibroblast growth factor and vascular endothelial growth
      factor was determined by enzyme immunoassay in the corresponding urine specimens.
      RESULTS: Urine samples from patients with BPH and prostate cancer increased
      bovine capillary endothelial cell proliferation by 13.1% and 15.1%, respectively,
      whereas urine from the control group showed a significantly lower angiogenic
      activity, increasing endothelial cell proliferation by only 0.7% (p = 0.001).
      Urinary basic fibroblast growth factor and vascular endothelial growth factor
      were highest in patients with BPH and lowest in the group with prostate cancer (p
      = 0.0001). CONCLUSIONS: Urine from patients with BPH and prostate cancer
      stimulates endothelial cell proliferative activity. The degree of endothelial
      cell stimulation does not correlate with the concentration of basic fibroblast
      growth factor or vascular endothelial growth factor. Whether the observed pro
      angiogenic activity is due to an increased production or release of (an) other
      angiogenic factor(s) and/or loss of (an) angiogenesis inhibitor(s), deserves
      further investigation.

PMID- 9649265
TI  - Two consecutive sets of transrectal ultrasound guided sextant biopsies of the
      prostate for the detection of prostate cancer.
AB  - PURPOSE: We investigated the role of performing 2 consecutive sets of transrectal
      ultrasound guided sextant biopsies of the prostate in a single office visit as
      the protocol for detecting prostate cancer in men presenting for the first time
      with an abnormal digital rectal examination and/or elevated serum prostate
      specific antigen (PSA). MATERIALS AND METHODS: A total of 137 consecutive men
      presenting for the first time with a clinically localized prostate nodule on
      digital rectal examination and/or elevated serum PSA based upon age specific
      reference ranges underwent 2 consecutive sets of sextant prostate biopsies under
      transrectal ultrasound guidance in a single office visit. The 2 sets of biopsies
      were processed and analyzed separately by pathologists. RESULTS: Adenocarcinoma
      of the prostate was diagnosed in 43 of the patients (31%) undergoing biopsy.
      Adenocarcinoma of the prostate was diagnosed in only the second set of biopsies
      in 13 cases (10%). High grade prostatic intraepithelial neoplasia without
      adenocarcinoma of the prostate was observed in 18 of the first set of biopsies
      (15%). High grade intraepithelial neoplasia without adenocarcinoma of the
      prostate was the only pathological diagnosis in the second set of biopsies in 3
      cases. The second set of biopsies provided important new clinical information
      related to prostate cancer in 20 cases (28%) and increased the number of cancers
      detected by 30%. In addition, 14 patients with high grade intraepithelial
      neoplasia who would have required a second set of biopsies were found not to have
      adenocarcinoma of the prostate. Prostate cancer was detected in 43, 27 and 24% of
      men with prostate volumes less than 30, 30 to 50 and greater than 50 cc,
      respectively. The percentage of prostate cancers detected only in the second set
      of biopsies was not significantly related to prostate size. CONCLUSIONS: Two
      consecutive sets of transrectal ultrasound guided sextant biopsies of the
      prostate performed in a single office visit represent a cost-effective biopsy
      strategy for men presenting with an abnormal digital rectal examination and/or
      elevated serum PSA. The benefits include increasing the detection of
      adenocarcinoma of the prostate and providing the recommended second set of
      biopsies for high grade intraepithelial neoplasia without increased morbidity or
      cost.

PMID- 9649266
TI  - Preliminary outcomes following cryosurgical ablation of the prostate in patients
      with clinically localized prostate carcinoma.
AB  - PURPOSE: Cryosurgical ablation of the prostate is a novel therapeutic modality
      that induces cell lysis in the prostate by direct application of low
      temperatures. We have been conducting an ongoing prospective pilot study of the
      use of cryosurgical prostate ablation in treating patients with nonmetastatic
      prostate adenocarcinoma since January 1993. Results in 145 consecutive patients
      with mean 36 months and minimum 12 months of followup are presented. MATERIALS
      AND METHODS: Accrual was open to patients with clinical stages T1a to T3c
      prostate adenocarcinoma. Pelvic lymph node dissections were recommended but not
      required for patients with prostate specific antigen (PSA) greater than 15
      ng./ml. before study entry. PSA changes, random prostate biopsy findings and
      morbidities after cryosurgical prostate ablation were recorded for each patient.
      RESULTS: Overall actuarial rates at 42 months for maintaining PSA less than 0.3
      and less than 1.0 were 59% and 66%, respectively. The overall actuarial
      progression-free rate at 60 months was 56%. Among 160 biopsies performed 16%
      showed some evidence of residual carcinoma. Overall crude rates of maintaining
      either a negative biopsy or PSA less than 0.3 at 6 and 24 months after
      cryosurgical prostate ablation were 87% and 73%, respectively. Significantly
      higher morbidities were seen in previously radiated patients undergoing
      cryosurgical prostate ablation compared to those with no prior radiation. Among
      nonradiated patients 85% experienced no significant morbidity after cryosurgical
      prostate ablation. CONCLUSIONS: Although preliminary, short-term outcomes after
      cryosurgical prostate ablation appear to be comparable to identical outcomes
      reported for external beam radiotherapy. Based on these results cryosurgical
      prostate ablation appears to be an effective therapeutic alternative for treating
      patients with localized prostate adenocarcinoma.

PMID- 9649267
TI  - Simple reinforcement for thin nephrostomy catheters.
AB  - PURPOSE: Nephrostomy catheters are prone to kinking or damage because the thin,
      flexible silicone tube is too vulnerable against mechanical stress even when the
      proximal end is carefully fixed. We developed a simple method to reinforce the
      outside part of a thin catheter protruding from the skin. MATERIALS AND METHODS:
      We treated 7 children with nephrostomy catheters or ureteral stents with a
      diameter of 8F or smaller. After insertion a large plastic tube was wrapped
      around the small catheter, and fixed to the skin and to the peripheral collection
      system with adhesive tape. RESULTS: Handling of the catheters improved and there
      was less need for re-fixation. CONCLUSIONS: Thin nephrostomy catheters can be
      effectively protected by wrapping them into a larger, outer tube after insertion.

PMID- 9649268
TI  - Nephron sparing management of Fraley's syndrome with a pyelopyelostomy.
AB  - PURPOSE: We describe a new technique for nephron sparing management of
      functionally significant vascular compression of the upper pole
      infundibulocaliceal system (Fraley's syndrome). MATERIALS AND METHODS: Two
      patients evaluated for debilitating, narcotic dependent flank pain had
      significant upper pole infundibulocaliceal obstruction resulting from aberrant
      major arterial branches entering the hilum dorsally. Reconstructive surgery
      consisted of dismembered pyelopyelostomy with transposition of the crossing
      vessels in both patients. RESULTS: Pain relief was immediate and complete in both
      patients. Followup radiographic evaluation at 1 and 12 months, respectively, has
      also documented resolution of the obstruction. CONCLUSIONS: Vascular compression
      causing obstruction of the superior infundibulum can cause debilitating pain.
      Pathophysiologically operative intervention can be nephron sparing and gratifying
      for the surgeon and the patient.

PMID- 9649269
TI  - Obstruction of the renal pelvis due to an insoluble blood clot after epsilon
      aminocaproic acid therapy: resolution with intraureteral streptokinase
      instillations.
AB  - PURPOSE: We demonstrate the effectiveness of intraureteral streptokinase
      instillations for the resolution of an insoluble blood clot in the renal pelvis.
      MATERIALS AND METHODS: A patient with renal adenocarcinoma had prolonged
      hematuria related to involvement of the "pyelum" by the tumor. An insoluble blood
      clot obstruction of the left renal collecting system developed as a consequence
      of epsilon aminocaproic acid therapy, which was treated with low dose
      streptokinase through a ureteral catheter. RESULTS: Complete resolution of the
      clot and obstruction occurred within 3 days of therapy. CONCLUSIONS: This
      relatively simple approach should be used for the treatment of obstruction before
      radical surgery is performed.

PMID- 9649270
TI  - Bladder leak point pressure: the measure for sphincterotomy success in spinal
      cord injured patients with external detrusor-sphincter dyssynergia.
AB  - PURPOSE: Transurethral resection of the external sphincter in patients with
      spinal cord injury and detrusor-external sphincter dyssynergia has high failure
      and reoperation rates. Retrospectively we examined elevated bladder leak point
      pressure after transurethral resection of the external sphincter as an indicator
      of failure. MATERIALS AND METHODS: A total of 55 spinal cord injury patients
      (mean age 50 years) underwent 1 or more sphincter resections, most recently a
      mean of 11 years ago. We reviewed the most recent urodynamic studies for bladder
      leak point pressure, bladder compliance and persisting external detrusor
      sphincter dyssynergia. Each patient was assessed for the presence of an
      indwelling catheter, upper tract damage, stones, bacteriuria, autonomic
      dysreflexia and vesicoureteral reflux. The incidence of each of these urodynamic
      and clinical parameters among patients with bladder leak point pressure less than
      40 cm. water was compared to the incidence among those with bladder leak point
      pressure greater than 40 cm. water. RESULTS: Patients with bladder leak point
      pressure greater than 40 cm. water had a significantly higher incidence of upper
      tract damage (p = 0.021) and persisting external detrusor-sphincter dyssynergia
      (p = 0.00008). The incidence of an indwelling catheter was no different between
      patients with bladder leak point pressure less than and greater than 40 cm.
      water. CONCLUSIONS: Bladder leak point pressure greater than 40 cm. water is a
      valid indicator of failure of transurethral resection of the external sphincter
      since there is a significantly higher incidence of upper tract damage and
      persisting external detrusor-sphincter dyssynergia in these patients. Patients
      with favorable urodynamic parameters after transurethral resection of the
      external sphincter but with indwelling catheters were poorly selected for this
      procedure. Furthermore, those without an indwelling catheter after transurethral
      resection of the external sphincter may still have adverse urodynamic parameters
      and are at significant risk for upper tract damage.

PMID- 9649271
TI  - Anuria and acute renal failure resulting from indinavir sulfate induced
      nephrolithiasis.

PMID- 9649272
TI  - Perinephric abscess masquerading as an angiomyolipoma.

PMID- 9649273
TI  - Shock wave lithotripsy during pregnancy: a successful clinical experiment.

PMID- 9649274
TI  - Lymphoepithelioma-like carcinoma of the ureter.

PMID- 9649275
TI  - Ureteral intussusception by invasive transitional cell carcinoma.

PMID- 9649276
TI  - Metastatic Crohn's disease involving penile skin.

PMID- 9649277
TI  - Primary leiomyosarcoma of the epididymis and late recurrence on the penis.

PMID- 9649278
TI  - Subspecialization, recruitment and retirement trends of American urologists.
AB  - PURPOSE: Trends of urology workforce, subspecialization, recruitment practices,
      retirement planning, practice characteristics and managed care impacts in the
      United States were assessed. MATERIALS AND METHODS: In February 1996 the
      executive interviewing branch of The Gallup Organization selected randomly and
      interviewed by telephone 507 practicing urologists in the United States who had
      provided urological patient care for more than 20 hours per week, practiced in
      1995 and completed a urological residency program. RESULTS: Several important
      issues emerged. Urologists think we may be training too many urologists,
      subspecialty board certification would be a divisive issue to urology as a whole
      and 90% of urologists have an active retirement plan, although 23% are not
      funding the plan fully. CONCLUSIONS: The American Urological Association Gallup
      Poll, as refined by the Health Policy Survey and Research Committee, continues to
      be a unique and valuable tool in assessing practice patterns, gathering
      demographic data and measuring opinions of the American urologist. This
      information will help us chart our way to the twenty-first century.

PMID- 9649279
TI  - Re: Bilateral ureteral obstruction after asymptomatic appendicitis.

PMID- 9649280
TI  - Re: Bladder prolapse in a female infant with complete epispadias.

PMID- 9649281
TI  - Re: The current level of involvement of urological trainees and faculty in
      clinical kidney transplantation in the United States and Canada.

PMID- 9649282
TI  - Report of the American Society of Nephrology meetings.
AB  - PURPOSE: We summarize presentations on topics of interest to the pediatric
      urologist from the annual meeting of the American Society of Nephrology, November
      1996. MATERIALS AND METHODS: We reviewed all abstracts submitted for presentation
      and subsequently published in abstract form. Only those abstracts containing
      information pertinent to the field of pediatric urology were summarized for this
      report. RESULTS: A total of 24 abstracts addressing a variety of topics were
      summarized. Obstructive uropathy was represented by the greatest number of papers
      and reflects the multiple investigative efforts currently evaluating the cellular
      aspects of this disorder. The genetic basis of hypercalciuria and the impact of
      water metabolism on nephroliathisis were also discussed. CONCLUSIONS: Clinical
      and basic research activities that are of mutual interest to pediatric urologists
      and nephrologists are being conducted. The topic of obstructive uropathy has
      received the greatest attention during the last year. However, additional
      research, potentially collaborative in nature, on topics such as nephroliathisis
      and reflux nephropathy should be encouraged.

PMID- 9649283
TI  - 99mTechnetium-dimercapto-succinic acid renal scan in the evaluation of potential
      long-term renal parenchymal damage associated with extracorporeal shock wave
      lithotripsy in children.
AB  - PURPOSE: Extracorporeal shock wave lithotripsy (ESWL) has been reported as
      efficient and safe in children. Because of reports of renal parenchymal damage in
      adults, this study was designed to assess the effects of ESWL in pediatric
      kidneys evaluated before and after treatment with (99m)technetium dimercapto
      succinic acid (DMSA) renal scan. MATERIALS AND METHODS: A total of 15 children, 9
      months to 15 years old (mean age 6.5 years), underwent ESWL treatment for
      urolithiasis. Evaluation imaging included plain abdominal radiography, excretory
      urogram and/or renal sonography. DMSA renal scan was performed 24 hours before
      ESWL and at least 6 months after treatment. RESULTS: ESWL was performed in 1
      session for 8 patients, 2 sessions for 6 and 3 sessions for 1, delivering a range
      of 600 to 3,000 shock waves per session. Treatment was successful in achieving
      stone-free status in 87% of the cases. Long-term followup (1 to 5 years) showed
      no blood pressure changes. On DMSA renal scan no acquired parenchymal scar was
      identified at least 6 months after ESWL treatment. CONCLUSIONS: The efficacy of
      ESWL in treating pediatric urolithiasis is confirmed. Renal parenchymal trauma
      associated with ESWL does not appear to cause long-term lesions identifiable by
      DMSA renal scan.

PMID- 9649284
TI  - Transverse retubularized ileum: early clinical experience with a new second line
      Mitrofanoff tube.
AB  - PURPOSE: Transverse retubularization of small ileal segments has been described
      as a new time and labor saving variation of the Mitrofanoff principle in a dog
      model with good functional results. We report our initial clinical experience
      with this technique. MATERIALS AND METHODS: From May 1996 through January 1997 a
      new technique of channel formation for intermittent catheterization was applied
      in 9 children (1 to 16 years old) and 7 adults (18 to 56) with various
      abnormalities of the lower urinary tract. The new method was used in primary
      reconstruction of the lower urinary tract and in revision procedures. An ileal
      segment 2 cm. long was excised. The bowel wall was opened longitudinally about 1
      cm. from the mesentery. The resulting rectangle was retubularized over a 14F
      catheter in transverse direction. The longer portion of the tube was implanted
      submucosally into the native bladder, the augmented bladder or an intestinal
      reservoir. The shorter portion was used to form the stoma. In 4 patients we
      created a double tube. RESULTS: Of the patients 13 (81%) are completely continent
      day and night with easy catheterization postoperatively. In 2 cases of tunnel
      failure continuous leakage required reimplantation of the intact ileal tube to
      achieve continence. Minor leakage with bladder fullness in an 11-year-old boy
      could be obviated by adjusting the interval of catheterization. CONCLUSIONS: With
      the advantage of constant availability, minimal loss of bowel, relative
      simplicity (no mesentery interfering with implantation, high tube mobility),
      minimized risk of stone formation (no staples), reliable continence (no leak
      point) and easy catheterization (longitudinal folds), this straightforward
      technique is an excellent second choice use of the Mitrofanoff principle.

PMID- 9649285
TI  - Alternatives to appendix in construction of a Mitrofanoff stoma.

PMID- 9649286
TI  - Reconstruction and undiversion of the short or severely dilated ureter: the
      antireflux ileal nipple revisited.
AB  - PURPOSE: Patients undergoing reconstruction of short or severely dilated
      aperistaltic ureters are at significant risk for mechanical or functional
      obstruction and reflux, particularly when the ureters are being reimplanted into
      gastric or intestinal segments. For this problem we describe a simple handsewn,
      "stapleless" antireflux ileal nipple, which serves as a useful bridge between a
      short ureter and the bladder or reservoir. MATERIALS AND METHODS: A total of 12
      patients, 4 to 42 years old (mean age 19), 9 with severely dilated and 3 with
      short ureters have received the stapleless antireflux ileal nipple as part of
      various reconstructive efforts. Briefly, a 12 to 15 cm. segment of ileum is
      isolated and the mesentery is stripped from the middle 8 cm. of the isolated
      segment, preserving the blood supply to the proximal and distal 2 cm. of ileum.
      Intussusception is created and maintained with multiple (5 to 7) circumferential
      rows of 4 to 6 interrupted seromuscular stitches of 3-zero silk. RESULTS: Mean
      followup is 27.5 months (range 6 to 60). Upper tract dilatation has stabilized or
      improved in all patients, deteriorating temporarily in 1 who had distal nipple
      stenosis. All patients underwent followup video urodynamic studies, which
      demonstrated no reflux. Nipple related complications included nipple stenosis in
      1 patient and dessusception in another. Both complications were corrected without
      sequelae. Ureteroileal stenosis or stone formation has not occurred. CONCLUSIONS:
      The stapleless antireflux ileal nipple is safe and reliable in preventing reflux.
      It is a versatile adjunct to urinary reconstruction in patients with short or
      severely dilated, aperistaltic ureters in whom the alternative of a tapered
      reimplantation into a segment of bowel or stomach poses a significant
      complication threat.

PMID- 9649287
TI  - Soluble interleukin-2 receptor in children with reflux nephropathy.
AB  - PURPOSE: Serum soluble interleukin-2 receptor level is a sensitive and
      quantitative marker of lymphocyte activation. We determined levels of serum
      soluble interleukin-2 receptor in children with reflux nephropathy to evaluate
      its clinical significance in the prediction for the progression of renal
      injuries. MATERIALS AND METHODS: Serum soluble interleukin-2 receptor values were
      determined in 63 children with reflux nephropathy. The group consisted of 37 boys
      and 26 girls 10 to 18 years old. T cells (naive and memory), B cells and
      macrophages were evaluated immunohistochemically in the scarred kidneys of 4
      other patients (3 boys and 1 girl 5 to 16 years old) who underwent nephrectomy
      due to severe reflux nephropathy with little function seen on (99m)technetium
      dimercapto-succinic acid (DMSA) renal scan. Levels of serum soluble interleukin-2
      receptor were measured by an enzyme-linked immunosorbent assay. We simultaneously
      determined serum levels of creatinine and beta2-microglobulin, and urinary levels
      of alpha1-microglobulin and microalbumin. Individual functions of the right and
      left kidneys were estimated by renal dimercaptosuccinic acid uptake. RESULTS:
      Levels of serum soluble interleukin-2 receptor in the patients who had low total
      uptake of DMSA (right uptake plus left uptake) were significantly higher than
      those from patients with normal total uptake. Levels of serum soluble interleukin
      2 receptor correlated significantly with levels of creatinine (r=0.616, p
      <0.0001) and beta2-microglobulin (r=0.803, p <0.0001), and levels of urinary
      alpha1-microglobulin (r=0.753, p <0.0001) and microalbumin (r=0.673, p <0.0001).
      A significant negative correlation was observed between levels of serum soluble
      interleukin-2 receptor and total DMSA uptake values (right uptake plus left
      uptake r=-0.678, p <0.0001). In the scarred kidneys leukocyte infiltrates were
      markedly increased in fibrosed spaces. The predominant cell type in these lesions
      was memory T cells. CONCLUSIONS: These results suggest that elevated levels of
      serum soluble interleukin-2 receptor are likely to reflect activated T cells in
      the kidneys of patients with reflux nephropathy and may be a useful predictor of
      progression of renal injury in these children.

PMID- 9649288
TI  - Analysis of testicular migration during the fetal period in humans.
AB  - PURPOSE: We present an analysis concerning the testicular migration and its
      position correlated to body weight, crown-rump length and gestational age during
      the fetal period in humans without congenital abnormalities. MATERIALS AND
      METHODS: We studied bilaterally 142 testes taken from 71 fresh human fetuses
      between 10 and 35 weeks after conception. The fetuses were also evaluated in
      regard to crown-rump length and body weight. The position of the testes was
      correlated to the fetal parameters. RESULTS: In 37 fetuses (74 testes) at 10 to
      23 weeks after conception only 7 testes (9.45%) had migrated from the abdomen and
      were situated in the inguinal canal, in 19 fetuses (38 testes) at 24 to 26 weeks
      after conception 22 testes (57.9%) had migrated from the abdomen and in 9 fetuses
      (18 testes) at 27 to 29 weeks after conception only 3 testes (16.7%) had not
      descended to the scrotum. The testes had not descended into the scrotum in any
      fetus weighing 990 gm. or less and with a crown-rump length of 24.5 cm. or less.
      On the other hand, in all fetuses weighing more than 1,220 gm. and with a crown
      rump length of more than 27.5 cm. the testis was in the scrotum. CONCLUSIONS:
      Until 23 weeks after conception the majority of testes remain in the abdomen. The
      more intense migration of the testes through the inguinal canal occurred between
      21 and 25 weeks after conception. After 30 weeks after conception all testes were
      descended to the scrotum in all fetuses.

PMID- 9649289
TI  - Immunolocalization of apolipoprotein D, androgen receptor and prostate specific
      antigen in early stage prostate cancers.
AB  - PURPOSE: To determine the cellular distribution and levels of immunohistochemical
      staining for apolipoprotein D (Apo-D), prostate specific antigen (PSA) and
      androgen receptor (AR) in early stage prostate cancers. MATERIALS AND METHODS:
      Cellular distribution of Apo-D, PSA and AR in 30 stage A/B prostate cancers and
      in non-malignant glandular tissue contained in the same sections was detected
      immunohistochemically, and staining was evaluated by computerized video image
      analysis. RESULTS: Staining for Apo-D (percentage positive cellular area) was
      significantly increased in tumor cells of early stage prostate cancers compared
      with non-malignant glandular tissue. PSA and AR were present at high levels in
      both early stage prostate tumors and non-malignant prostate. CONCLUSIONS:
      Malignant transformation in the prostate is associated with increased cellular
      levels of Apo-D.

PMID- 9649290
TI  - Sex differences in function and distribution of beta-adrenoceptors in rabbit
      urinary bladder.
AB  - PURPOSE: To examine whether there are sex-related differences in urinary bladder
      function, we evaluated the function and distribution of beta-adrenoceptor in the
      male and female rabbit urinary bladder. MATERIALS AND METHODS: Ten male and ten
      female rabbits were studied. The function and distribution of beta-adrenoceptors
      were studied by measuring changes in contractile forces from isoproterenol, a
      beta-adrenoceptor agonist, and forskolin, an adenylate cyclase activator, and by
      measuring beta-adrenoceptor densities using radioligand receptor binding
      techniques. RESULTS: Isoproterenol caused significantly greater relaxation in
      female trigonal muscles than in male trigonal muscles. It caused similar
      relaxation responses in the male and female detrusors. The Bmax values for
      [3H]dihydroalprenolol (DHA) binding in trigonal muscles were significantly higher
      in the female than in the male, whereas Bmax values for [3H]DHA binding in the
      male and the female detrusor were similar. In contrast, forskolin caused
      similarly marked relaxations in the male and the female detrusor and trigonal
      muscles. CONCLUSION: These findings demonstrate that there are sex-related
      differences in the function and the distribution of beta-adrenoceptors in rabbit
      trigonal smooth muscles.

PMID- 9649291
TI  - Loss of fimbrial adhesion with the addition of Vaccinum macrocarpon to the growth
      medium of P-fimbriated Escherichia coli.
AB  - PURPOSE: Vaccinium macrocarpon--the American cranberry--irreversibly inhibits the
      expression of P-fimbriae of E. coli. Further effects on the function and
      expression of P-fimbriae were studied by growing P-fimbriated E. coli in solid
      media laced with cranberry juice. METHODS: Cranberry concentrate at pH 7.0 was
      added to CFA medium to a final concentration of 25%. E. coli strains JR1 and DS17
      were plated on this medium with a plain CFA control and incubated at 37C.
      Cultures were tested for ability to agglutinate P-receptor specific beads.
      Bacteria were washed in PBS and agglutination retested. Cultures were also
      replated on plain CFA agar and rechecked for their ability to agglutinate.
      Transmission electron micrographs were performed on positive control and test
      bacteria. RESULTS: For E. coli strain JR1, P-fimbrial agglutination was inhibited
      after the third plating. DS17 was fully inhibited after the second plating.
      Washing in PBS did not affect agglutination, but replating on CFA agar allowed
      agglutination to recur. Electron micrographic study of control populations
      confirmed fimbriae. Fully inhibited bacteria had a 100% reduction in expression
      of fimbriae. Additionally, inhibited bacteria showed cellular elongation.
      CONCLUSIONS: Cranberry juice irreversibly inhibits P-fimbriae. Electron
      micrographic evidence suggests that cranberry juice acts on the cell wall
      preventing proper attachment of the fimbrial subunits or as a genetic control
      preventing the expression of normal fimbrial subunits or both.

PMID- 9649292
TI  - Renal actions of endothelin-1 under endothelin receptor blockade by BE-18257B.
AB  - PURPOSE: Endothelin-1 (ET-1), a peptide produced by the vascular endothelium,
      causes profound renal vasoconstriction by binding to ET-A receptors. The present
      study examined the renal actions of ET-1 after ET-A receptors were blocked by BE
      18257B to unmask the functions of ET-B receptors. MATERIALS AND METHODS: Renal
      hemodynamics and clearance measurements were obtained in anesthetized dogs after
      intrarenal infusion of BE-18257B at 100 ng./kg./min. (Group 1), after intrarenal
      infusion of ET-1 at 2 ng./kg./min. (Group 2), or after intrarenal infusion of ET
      1 superimposed on BE-18257B (Group 3). RESULTS: In Group 1, BE-18257B infusion
      did not alter arterial pressure, renal blood flow (RBF), GFR or tubular function.
      In Group 2, ET-1 infusion led to a significant decrease in RBF and GFR (37 and
      40%, respectively) without altering arterial pressure. Urinary volume and sodium
      excretion were not changed but osmolality decreased significantly. In Group 3, BE
      18257B infusion significantly attenuated the decrease in RBF caused by ET-1 and
      increased GFR by 40% without altering arterial pressure, associated with
      significant diuresis and natriuresis. CONCLUSION: Renal vasoconstriction caused
      by ET-1 is attenuated by ET-A receptor blockade with BE-18257B, which unmasks the
      hemodynamic and tubular actions of ET-B receptors. As a result, it limits the ET
      1 induced decrease in RBF and raises GFR, and leads to a diuresis and
      natriuresis.

PMID- 9649293
TI  - Lidocaine prevents noxious excitation of bladder afferents induced by
      intravesical capsaicin without interfering with the ensuing sensory
      desensitization: an experimental study in the rat.
AB  - PURPOSE: The effects of the local anesthetic lidocaine on the noxious excitation
      and subsequent desensitization of bladder sensory fibers, produced by
      intravesical capsaicin, were evaluated through c-fos activation in the spinal
      cord. MATERIALS AND METHODS: Noxious excitation was demonstrated by counting Fos
      immunoreactive (IR) cells occurring in the rat spinal cord 2 hours after
      intravesical administration of 1 mM. capsaicin, preceded or not by 2% lidocaine.
      Desensitization was studied by comparing the number of Fos-IR cells induced by 1%
      acetic acid in rats treated 24 hours before with 1 mM. intravesical capsaicin
      preceded or not by 2% lidocaine. RESULTS: Lidocaine instilled previously markedly
      reduced the number of Fos-IR spinal cells responding to capsaicin-induced bladder
      afferent excitation. Numbers of Fos-IR cells induced by acetic acid instillation
      in bladders desensitized by capsaicin administrated 24 hours before were not
      changed by lidocaine application prior to capsaicin. CONCLUSIONS: These findings
      suggest that local anesthetic pretreatment of the bladder with lidocaine reduces
      the capsaicin-induced noxious excitation of the sensory fibers without decreasing
      their subsequent desensitization.

PMID- 9649294
TI  - Effects of MK-801 on bladder overactivity in rats with cerebral infarction.
AB  - PURPOSE: Our objective was to evaluate the underlying mechanisms of neurogenic
      voiding dysfunction following cerebral infarction. MATERIALS AND METHODS: The
      left middle cerebral artery (MCA) was occluded using 4-0 monofilament nylon
      thread in male S-D rats. Cystometric examination was performed in unanesthetized
      and urethane-anesthetized rats through a catheter chronically implanted in the
      dome of the bladder. RESULTS: Bladder capacity of unanesthetized or urethane
      anesthetized rats was significantly reduced just after occlusion of the left MCA;
      2 weeks after the occlusion, the capacity was less than half that in sham
      operated rats. Intravenous administration of N-methyl-d-aspartate (NMDA) receptor
      antagonist MK-801 to the unanesthetized sham-operated rats led to a marked dose
      dependent decrease in bladder capacity. Its administration to unanesthetized rats
      with cerebral infarction resulted in a slight decrease in bladder capacity. In
      the urethane-anesthetized state, the bladder capacity of the rats with cerebral
      infarction was significantly increased by MK-801, 0.1 mg./kg., without inhibiting
      the contraction pressure or increasing the amount of residual urine. A high dose
      (1 mg./kg.) of MK-801 was required to increase the bladder capacity of sham
      operated rats. This led to an inhibition of contraction pressure and an increase
      in residual urine. CONCLUSION: Results in urethane anesthetized rats indicate
      that NMDA glutamatergic transmission is important in the overactivity of the
      bladder following a cerebral infarction. This model is useful in studying the
      neurogenic voiding dysfunction observed in patients with cerebrovascular disease.

PMID- 9649295
TI  - Change in bladder contractility associated with bladder overactivity in rats with
      cerebral infarction.
AB  - PURPOSE: To evaluate the contractile properties of overactive bladder from rats
      in the chronic stage of experimental cerebral infarction. MATERIALS AND METHODS:
      Cystometry was performed in conscious male S-D rats after inducing occlusion of
      the left middle cerebral artery. Bladder muscle strips were evaluated for force
      development in response to field stimulation, acetylcholine and KCl. By measuring
      the contractile response to field stimulation after adding atropine and
      alpha,beta-methylene-ATP, contributions of cholinergic and purinergic
      transmission were determined. RESULTS: Bladder capacity of cerebral-infarcted
      rats was <50% of the capacity of sham-operated rats and significantly less than
      that of sham-operated rats even 4 months after surgery. There was no significant
      difference in bladder weight between sham-operated rats and cerebral-infarcted
      rats. No differences in the contractile response of detrusor strips to field
      stimulation and acetylcholine, or in the relative contribution of cholinergic and
      purinergic transmission to the contractile response, were observed over time or
      between strips from sham-operated rats and cerebral-infarcted rats. KCl induced
      significantly less contraction in strips from 4 month infarcted rats than in
      strips from 4 month sham-operated rats, 2 week infarcted rats and 2 month
      infarcted rats. CONCLUSIONS: This animal model will be useful for chronic studies
      on the mechanism of detrusor hyperactivity (DH).

PMID- 9649296
TI  - Methotrexate resistance in human uroepithelial cells with p53 alterations.
AB  - PURPOSE: Bladder cancers are frequently treated with combination chemotherapy
      that includes methotrexate (MTX). The development of drug resistance is a common
      problem in treatment of bladder cancers. We tested if the status of p53 and/or
      pRb affects the development of MTX resistance in bladder epithelial cell lines.
      MATERIALS AND METHODS: We used two isogeneic sets of cell lines in which we
      manipulated the status of p53 and/or pRb by transformation with Human
      Papillomavirus (HPV) E6 and/or E7 or with a transdominant TP53 mutant
      (TP53(143)). One series of isogeneic origin was derived from normal human
      uroepithelial cells (HUC), and the other was derived from a human transitional
      cell carcinoma (TCC). Cell lines with p53 and/or pRb alterations were cultured
      for six months while increasing the MTX concentration in each line, as resistance
      developed. RESULTS: Two cell lines with both pRb and p53 alterations, alphaE6/E7
      HUC and alphaE7-HUCp53mu, acquired the greatest resistance (750 nM) to MTX. One
      line with p53 loss, E6-TCC#10, acquired intermediate resistance (500 nM), while
      two lines, alphaE7-HUC and E7-TCC#10, with altered pRb but wildtype p53, showed
      low levels of MTX resistance (125 nM and 80 nM, respectively). Two clear
      mechanisms of MTX resistance were identified. All five MTX resistant cell lines
      showed altered uptake of MTX. In addition, two of five MTX resistant cell lines,
      both with altered p53, showed dihydrofolate reductase (DHFR) amplification.
      CONCLUSIONS: p53 alteration increases the risk for development of drug resistance
      by both DHFR amplification and altered MTX transport in transformed human bladder
      epithelial cell lines.

PMID- 9649297
TI  - Effects of epidermal growth factor on the invasion activity of the bladder cancer
      cell line.
AB  - PURPOSE: Epidermal growth factor (EGF) is excreted in high concentrations in the
      urine and stimulates urothelial cell growth. The cultured bladder cancer cell
      line KU-1 was used to study the molecular mechanisms by which EGF affects
      urothelial tumor growth and invasion activity. MATERIALS AND METHODS: KU-1 cells
      were grown in cell culture in the presence or absence of EGF. Anchorage
      independent cell growth assays and Matrigel invasion assays were performed.
      Expression of cytokeratins was examined by Northern and Western blot analyses.
      Chloramphenicol acetyltransferase assays were used to determine whether EGF
      stimulated matrix metalloproteinase expression. RESULTS: EGF enhanced anchorage
      independent growth in soft agar and increased the number of cells penetrating
      into a Matrigel membrane. A transient transfection assay revealed that EGF
      increased the promoter activities of the matrix metalloproteinase 1 and 9 genes
      in KU-1 cells. Moreover, the morphology of KU-1 cells changed after the addition
      of EGF to the culture medium. Western and Northern blot analyses demonstrated
      that EGF decreased cytokeratin 19 expression, but did not affect expression of
      cytokeratin 8 or 18. CONCLUSION: EGF increased the invasive activity of KU-1
      bladder cancer cells in part by increasing the secretion of matrix
      metalloproteinases. Morphologic changes may result from altered composition of
      cytoskeletal proteins.

PMID- 9649298
TI  - Sensitivity of human prostatic carcinoma cell lines to low dose rate radiation
      exposure.
AB  - PURPOSE: Low dose rate radioemitters, such as 125I, 103Pd, and 89Sr, have been
      used both for local and systemic treatment of prostate cancer. Most normal cells
      exposed to ionizing radiation characteristically activate cell cycle checkpoints,
      resulting in cell cycle arrest at the G1/S and G2/M transition points. Cancer
      cells are typically quite sensitive to radiation killing late in the G2 phase of
      the replicative cell cycle. Furthermore, most cancer cells accumulating at the
      G2/M transition point as a result of low dose rate radiation exposure appear to
      become sensitive to further low dose rate irradiation. For this reason,
      protracted exposure of cancer cells to low dose rate radiation has been proposed
      to result in increased cancer cell killing as compared with brief exposures of
      cancer cells to high dose rate radiation. Since many human prostatic carcinomas
      contain somatic genome alterations targeting genes which affect the cell cycle
      and radiation-associated cell cycle checkpoints, we evaluated the effects of low
      dose rate radiation exposure on the cell cycle and on clonogenic survival for
      various human prostatic carcinoma cell lines. MATERIALS AND METHODS: Human
      prostatic carcinoma cells from the LNCaP, DU 145, PC-3, PPC-1, and TSU-Pr1 cell
      lines were exposed to low dose rate (0.25 Gy/hour) or high dose rate (60 Gy/hour)
      radiation in vitro and then assessed for radiation cytotoxicity by clonogenic
      survival assay. Cell cycle perturbations following protracted exposure to low
      dose rate radiation were evaluated using flow cytometry. RESULTS: For LNCaP
      cells, low dose rate radiation exposure resulted in an accumulation of cells at
      both the G1/S and the G2/M cell cycle transition points. For DU 145, PC-3, PPC-1,
      and TSU-Pr1 cells, treatment with low dose rate radiation triggered G2/M cell
      cycle arrest, but not G1/S arrest. Unexpectedly, the cell cycle redistribution
      pattern phenotypes observed, G1/S and G2/M cell cycle arrest versus G2/M arrest
      alone, appeared to have little effect on low dose rate radiation survival.
      Furthermore, while PC-3, PPC-1, and TSU-Pr1 cells exhibited increased cytotoxic
      sensitivity to low dose rate versus fractionated high dose rate radiation
      treatment, DU 145 and LNCaP cells did not. CONCLUSIONS: Radiation-associated
      pertubations in replicative cell cycle progression were not dominant determinants
      of low dose rate radiation killing efficacy in human prostate cancer cell lines
      in vitro.

PMID- 9649299
TI  - Improved detection of recurrent bladder cancer using the bard BTA stat test.

PMID- 9649301
TI  - Understanding the role of the essential Asp251 in cytochrome p450cam using site
      directed mutagenesis, crystallography, and kinetic solvent isotope effect.
AB  - Proton transfer in cytochromes P450 is a critical step in the activation of
      molecular oxygen. Extensive study of the P450cam active site has identified
      several residues that play a central role in dioxygen bond scission. A highly
      conserved carboxylate, aspartate-251 in P450cam in the distal helix I,
      participates in a series of hydrogen-bond/ion pairs near the molecular surface
      and has been implicated in the catalytic mechanism. Mutation of Asp251 is known
      to lower activity by 2 orders of magnitude and change the rate-limiting step in
      the catalytic cycle, suggesting a role for an acid functionality in generation of
      iron-oxygen reactive intermediates. The turnover rates of the Asp251Asn mutant in
      various protium-deuterium mixtures have been determined and show a significantly
      larger kinetic solvent isotope effect, with an overall magnitude of 10 compared
      to 1.8 for the wild-type P450cam. In addition, a much larger number of protons
      are involved in the rate-limiting step for the Asp251Asn mutant than in the wild
      type enzyme. These results indicate that Asp251 is an essential part of the
      normal proton delivery machinery required for O-O bond scission. The crystal
      structure of the Aps251Asn mutant obtained from data collected at cryogenic
      temperatures has been refined to 1.9 A. Key hydrogen bonds required to hold
      Asp251 in position have been broken which allows the mutant Asn251 side chain to
      swing out and away from the O2 binding site leading to a more open active site.
      This change could allow easier access by water and thus contribute to the
      observed kinetic solvent isotope effects.

PMID- 9649302
TI  - Active-site binding of glycosides by Thermomonospora fusca endocellulase E2.
AB  - The determination of the high-resolution structure of the Thermomonospora fusca
      endocellulase E2 catalytic domain makes it ideal for exploring cellulase
      structure-function relationships. Here we present binding parameters (Kd, DeltaH
      degrees, and DeltaS degrees) describing the interaction of E2 with 4
      methylumbelliferyl glycosides, determined by titrating the quenching of ligand
      fluorescence in equilibrium binding experiments. Quenched MU(Glc)2/E2 complexes
      were used as indicators in displacement titrations to measure the binding of
      natural glycosides and also of a nonhydrolyzable cellotetraose analogue. Binding
      of MU(Glc)2 and cellotriose were also determined by titration calorimetry. The
      results show that E2 binds glycosides exclusively in its active-site cleft, with
      high affinity and specificity. The observed patterns of ligand hydrolysis and the
      results with MU(Glc)2 as a substrate indicated that ligands bound to E2 with
      their nonreducing ends in position -2, consistent with the position of cellobiose
      in the E2cd structure. Polymerase chain reaction (PCR) mutagenesis of the
      conserved residue Tyr 73 (in E2 binding subsite -1) to Phe and Ser produced
      enzymes with lower activity but higher binding affinities, indicating that the
      volume of the subsite -1 binding pocket is crucial for enzyme function.
      Similarly, MUXylGlc (with its xylosyl unit located in position -1) bound with 100
      fold higher affinity than MU(Glc)2. These results are similar to those for the
      related Trichoderma reesei exocellulase CBH II. The binding data were compared
      with that previously reported for CBH II and interpreted in terms of the
      functional differences between endo- and exocellulases.

PMID- 9649303
TI  - NMR solution structure of a DNA dodecamer duplex containing a cis
      diammineplatinum(II) d(GpG) intrastrand cross-link, the major adduct of the
      anticancer drug cisplatin.
AB  - The structure of the DNA duplex dodecamer, d(CCTCTGGTCTCC. GGAGACCAGAGG),
      containing the cisplatin d(GpG) 1,2-intrastrand cross-link at the position
      denoted by asterisks, was determined in solution by high-resolution 2D NMR
      spectroscopy and restrained molecular dynamics refinement. The cis
      [Pt(NH3)2?d(GpG-N7(1), N7(2))?] lesion causes the adjacent guanine bases to roll
      toward one another by 49 degrees, leading to an overall helix bend angle of 78
      degrees. These features are more exaggerated than those observed in the X-ray
      crystal structure determined for the same platinated duplex [Takahara et al.
      (1995) Nature 377, 649-652]. A common property of the solution and crystal
      structures is the widening and flattening of the minor groove opposite the
      platinum adduct, affording geometric parameters resembling those found in A-form
      DNA. This deformation is especially noteworthy for the solution structure because
      its sugar puckers are primarily those of B-form DNA. The unwinding of the helix
      at the site of platination is 25 degrees. The curvature and shape of the
      platinated duplex are remarkably similar to those observed in DNA duplexes
      complexed by the HMG-domain proteins SRY and LEF-1. The structure reveals how
      cisplatin binding alters DNA in such a manner as to facilitate HMG-domain protein
      recognition.

PMID- 9649304
TI  - H11-H12 loop retinoic acid receptor mutants exhibit distinct trans-activating and
      trans-repressing activities in the presence of natural or synthetic retinoids.
AB  - Retinoids, such as the naturally occurring all-trans-retinoic acid (atRA) and
      synthetic ligand CD367 modulate ligand-dependent transcription through retinoic
      acid receptors (RARs). Retinoid binding to RAR is believed to trigger structural
      transitions in the ligand-binding domain (LBD), leading to helix H1 and helix H12
      repositioning and coactivator recruitment and corepressor release. Here, we
      carried out a detailed mutagenesis analysis of the H11-H12 loop (designated the L
      box) to study its contribution to hRARalpha activation process. Point mutations
      that reduced transactivation by atRA also reduced atRA-induced transrepression of
      AP1 transcription, correlating ligand-induced activation and repression. However,
      a correlation was not observed with these mutations when tested with another
      ligand CD367, a synthetic agonist with binding properties identical to those of
      atRA. Transcription was strongly inhibited in the presence of CD367 for some
      mutants, thus leading to an inverse agonist activity of this ligand. None of
      these mutations significantly altered binding affinity for either ligand,
      indicating that altered transcription was not caused by altered ligand binding by
      these mutations. Although simple correlations with transcriptional activities
      were not found, these mutations were also characterized by altered ligand-induced
      structural transitions, which were distinct for the atRA-hRARalpha or CD367
      hRARalpha complexes. These results indicate that amino acids in the L box are
      involved in specifying trans-repressive and trans-activating properties of the
      hRARalpha, and support the notion that different agonists induce distinct
      conformations in the LBD of the receptor.

PMID- 9649305
TI  - A single amino acid substitution changes ribonuclease 4 from a uridine-specific
      to a cytidine-specific enzyme.
AB  - The structural features underlying the strong uridine specificity of ribonuclease
      4 (RNase 4) are largely unknown. It has been hypothesized that the negatively
      charged alpha-carboxylate is close to the pyrimidine binding pocket, due to a
      unique C-terminal deletion. This would suppress the cleavage of cytidine
      containing substrates [Zhou, H.-M., and Strydom, D. J. (1993) Eur. J. Biochem.
      217, 401-410]. Replacement of the alpha-carboxylate by an alpha-carboxamide in a
      fragment complementation system decreased both (kcat/Km)CpA and (kcat/Km)UpA ,
      thus refuting the hypothesis. However, model building showed that the deletion
      allowed the side chain of Arg-101 to reach the pyrimidine binding pocket. From
      the 386-fold reduction in (kcat/Km)UpA in RNase 4;R101N, it is concluded that
      this residue functions in uridine binding, analogous to Ser-123 in RNase A. In
      addition, it may have an effect on Asp-80. The 2-fold increase in (kcat/Km)CpA in
      the mutant R101N and the close proximity of the side chains of Arg-101 and Asp-80
      suggested that the latter could be involved in suppressing CpA catalysis. The
      substrate specificity of RNase 4;D80A was completely reversed: (kcat/Km)UpA
      decreased 159-fold, whereas (kcat/Km)CpA increased 233-fold. The effect on CpA
      was unexpected, because the corresponding residue in bovine pancreatic RNase A
      (Asp-83) hardly affects cytidine-containing substrates. Furthermore, the residue
      is conserved in nearly all sequences of mammalian RNase 1. Thus, an evolutionary
      highly conserved residue does not necessarily function in the same way in
      homologous enzymes. A model, which proposes that the structure of RNase 4 has
      been optimized to permanently fix the position of Asp-80 and impede its movement
      away from the pyrimidine binding pocket, is presented.

PMID- 9649306
TI  - Novel water-mediated hydrogen bonds as the structural basis for the low oxygen
      affinity of the blood substitute candidate rHb(alpha 96Val-->Trp).
AB  - One of the most promising approaches for the development of a synthetic blood
      substitute has been the engineering of novel mutants of human hemoglobin (Hb) A
      which maintain cooperativity, but possess lowered oxygen affinity. We describe
      here two crystal structures of one such potential blood substitute, recombinant
      (r) Hb(alpha 96Val-->Trp), refined to 1.9 A resolution in an alpha-aquomet, beta
      deoxy T-state, and to 2.5 A resolution in a carbonmonoxy R-state. On the basis of
      molecular dynamics simulations, a particular conformation had been predicted for
      the engineered Trp residue, and the lowered oxygen affinity had been attributed
      to a stabilization of the deoxy T-state interface by alpha 96Trp-beta 99Asp
      hydrogen bonds. Difference Fourier maps of the T-state structure clearly show
      that alpha 96Trp is in a conformation different from that predicted by the
      simulation, with its indole side chain directed away from the interface and into
      the central cavity. In this conformation, the indole nitrogen makes novel water
      mediated hydrogen bonds across the T-state interface with beta 101Glu. We propose
      that these water-mediated hydrogen bonds are the structural basis for the lowered
      oxygen affinity of rHb(alpha 96Val-->Trp), and discuss the implications of these
      findings for future molecular dynamics studies and the design of Hb mutants.

PMID- 9649307
TI  - Contribution of domain interface residues to the stability of antibody CH3 domain
      homodimers.
AB  - Dimers of CH3 domains from human IgG1 were used to study the effect of mutations
      constructed at a domain-domain interface upon domain dissociation and unfolding,
      "complex stability". Alanine replacement mutants were constructed on one side of
      the interface for each of the sixteen interdomain contact residues by using a
      single-chain CH3 dimer in which the carboxyl terminus of one domain was joined to
      the amino terminus of the second domain via a (G4S)4 linker. Single-chain
      variants were expressed in Escherichia coli grown in a fermentor and recovered in
      yields of 6-90 mg L-1 by immobilized metal affinity chromatography. Guanidine
      hydrochloride-induced denaturation was used to follow domain dissociation and
      unfolding. Surprisingly, the linker did not perturb the complex stability for
      either the wild type or two destabilizing mutants. The CH3 domain dissociation
      and unfolding energetics are dominated by six contact residues where
      corresponding alanine mutations each destabilize the complex by >2.0 kcal mol-1.
      Five of these residues (T366, L368, F405, Y407, and K409) form a patch at the
      center of the interface and are located on the two internal antiparallel beta
      strands. These energetically key residues are surrounded by 10 residues on the
      two external beta-strands whose contribution to complex stability is small (three
      have a Delta DeltaG of 1.1-1.3 kcal mol-1) or very small (seven have a Delta
      DeltaG of </=0.7 kcal mol-1). Thus, at the center of the CH3 structural interface
      there is a small "functional interface" of residues that make significant
      contributions to complex stability.

PMID- 9649308
TI  - The role of profilin in actin polymerization and nucleotide exchange.
AB  - Properties of human profilin I mutated in the major actin-binding site were
      studied and compared with wild-type profilin using beta/gamma-actin as
      interaction partner. The mutants ranged in affinity, from those that only weakly
      affected polymerization of actin to one that bound actin more strongly than wild
      type profilin. With profilins, whose sequestering activity was low, the
      concentration of free actin monomers observed at steady-state of polymerization
      [Afree], was close to that seen with actin alone ([Acc], critical concentration
      of polymerization). Profilin mutants binding actin with an intermediate affinity
      like wild-type profilin caused a lowering of [Afree] as compared to [Acc],
      indicating that actin monomers and profilin:actin complexes participate in
      polymer formation. With a mutant profilin, which bound actin more strongly than
      the wild-type protein, an efficient sequestration of actin was observed, and in
      this case, the [Afree] at steady state was again close to [Acc], suggesting that
      the mutant profilin:actin had a greatly lowered ability to incorporate actin
      subunits at the (+)-end. The results from the kinetic and steady-state
      experiments presented are consonant with the idea that profilin:actin complexes
      are directly incorporated at the (+)-end of actively polymerizing actin
      filaments, while they do not support the view that profilin facilitates polymer
      formation.

PMID- 9649309
TI  - Apolipoprotein(a) binds to low-density lipoprotein at two distant sites in
      lipoprotein(a).
AB  - Lipoprotein(a) [Lp(a)] consists of low-density lipoprotein (LDL) and
      apolipoprotein(a) [apo(a)] linked with a disulfide bond. Scanning force
      microscopy (SFM) of Lp(a) showed, for the first time, a belt-like structure of
      apo(a) with both ends attached to a spherical LDL. The two ends of apo(a) were
      bound to the LDL sphere at two distant sites. Occasionally, the ends were
      attached to two touching spheres. Under the same imaging conditions, LDL appeared
      as individual spheres. Electron microscopy (EM) studies of Lp(a) by several
      groups over the past decade failed to reveal this belt-like structure of apo(a).
      Images of isolated apo(a) in air or in phosphate buffer showed apo(a) as
      individual belts, and these belts tended to crowd together. Lp(a) formed leaf
      like aggregates; apo(a) aggregates were fishnet-like, whereas LDL aggregates were
      less characteristic. Quantitative analysis of Lp(a) showed the diameter of the
      LDL to be 24.8 +/- 8.7 nm (n = 46), which is close to the reported value of 24.2
      +/- 4.2 nm found with EM. The length of the belts attached to the spheres was
      measured to be 173.5 +/- 6.6 nm (n = 15). I also found, by using a functionalized
      tip, that the interaction force between apo(a) and its ligand, lysine, was
      related to the ionic strength of the bulk solution. This force can be reduced by
      the presence of epsilon-aminocaproic acid.

PMID- 9649310
TI  - Active site modifications in a double mutant of liver alcohol dehydrogenase:
      structural studies of two enzyme-ligand complexes.
AB  - The oxidation of alcohol to aldehyde by horse liver alcohol dehydrogenase (LADH)
      requires the transfer of a hydride ion from the alcohol substrate to the cofactor
      nicotinamide adenine dinucleotide (NAD). A quantum mechanical tunneling
      contribution to this hydride transfer step has been demonstrated in a number of
      LADH mutants designed to enhance or diminish this effect [Bahnson, B. J., et al.
      (1997) Proc. Natl. Acad. Sci. U.S.A. 94, 12797-12802]. The active site double
      mutant Phe93 --> Trp/Val203 --> Ala shows a 75-fold reduction in catalytic
      efficiency relative to that of the native enzyme, and reduced tunneling relative
      to that of either single mutant. We present here two crystal structures of the
      double mutant: a 2.0 A complex with NAD and the substrate analogue
      trifluoroethanol and a 2.6 A complex with the isosteric NAD analogue CPAD and
      ethanol. Changes at the active site observed in both complexes are consistent
      with reduced activity and tunneling. The NAD-trifluoroethanol complex
      crystallizes in the closed conformation characteristic of the active enzyme.
      However, the NAD nicotinamide ring rotates away from the substrate, toward the
      space vacated by replacement of Val203 with the smaller alanine. Replacement of
      Phe93 with the larger tryptophan also produces unfavorable steric contacts with
      the nicotinamide carboxamide group, potentially destabilizing hydrogen bonds
      required to maintain the closed conformation. These contacts are relieved in the
      second complex by rotation of the CPAD pyridine ring into an unusual syn
      orientation. The resulting loss of the carboxamide hydrogen bonds produces an
      open conformation characteristic of the apoenzyme.

PMID- 9649311
TI  - Insights into the mechanism of catalysis by the P-C bond-cleaving enzyme
      phosphonoacetaldehyde hydrolase derived from gene sequence analysis and
      mutagenesis.
AB  - Phosphonoacetaldehyde hydrolase (phosphonatase) catalyzes the hydrolysis of
      phosphonoacetaldehyde to acetaldehyde and inorganic phosphate. In this study, the
      genes encoding phosphonatase in Bacillus cereus and in Salmonella typhimurium
      were cloned for high-level expression in Escherichia coli. The kinetic properties
      of the purified, recombinant phosphonatases were determined. The Schiff base
      mechanism known to operate in the B. cereus enzyme was verified for the S.
      typhimurium enzyme by phosphonoacetaldehyde-sodium borohydride-induced
      inactivation and by site-directed mutagenesis of the catalytic lysine 53. The
      protein sequence inferred from the B. cereus phosphonatase gene was determined,
      and this sequence was used along with that from the S. typhimurium phosphonatase
      gene sequence to search the primary sequence databases for possible structural
      homologues. We found that phosphonatase belongs to a novel family of hydrolases
      which appear to use a highly conserved active site aspartate residue in covalent
      catalysis. On the basis of this finding and the known stereochemical course of
      phosphonatase-catalyzed hydrolysis at phosphorus (retention), we propose a
      mechanism which involves Schiff base formation with lysine 53 followed by
      phosphoryl transfer to aspartate (at position 11 in the S. typhimurium enzyme and
      position 12 in the B. cereusphosphonatase) and last hydrolysis at the imine C(1)
      and acyl phosphate phosphorus.

PMID- 9649312
TI  - NMR solution structure of the oxidized form of MerP, a mercuric ion binding
      protein involved in bacterial mercuric ion resistance.
AB  - Mercuric ions are toxic to living organisms because of their strong affinity for
      cysteine residues in proteins. Some bacteria have developed a resistance
      mechanism whereby Hg2+ is transported into the cytoplasm and reduced to Hg0. One
      of the proteins involved in the transport of mercuric ion is the periplasmic
      binding protein MerP, which can exist both as oxidized (disulfide) and as reduced
      (dithiol) forms. Only the reduced form with Cys-17 and Cys-14 residues as free
      thiols is a potent receptor for mercuric ion. In this work the solution structure
      of the oxidized form of MerP has been determined by multidimensional NMR
      spectroscopy and compared to the NMR structures of the previously published
      structures of the reduced and mercury-bound forms of MerP. The mercury-bound and
      oxidized forms have similar tertiary structures, whereas in the reduced form
      there is a large rearrangement of the mercuric ion binding loop and the nearby
      loop comprising residues 38-41. The structural arrangement of the latter loop
      seems to be important for the stabilization of the surface location of the
      cysteine-containing loop. In the reduced form at low pH the cysteine-containing
      loop adopts a conformation similar to what is observed in the oxidized and
      mercury-bound forms. The oxidized form also differs with respect to the other two
      forms in the relative positions of some of the alpha-helices and beta-strands.
      Structural differences between the oxidized and reduced forms may help explain
      why the reduced form is stable in the periplasm, which is considered to be an
      oxidizing environment.

PMID- 9649313
TI  - 13C relaxation and dynamics of the purine bases in the iron responsive element
      RNA hairpin.
AB  - The iron responsive element (IRE) RNA hairpin contains a conserved six-nucleotide
      loop. The NMR structure of this loop showed that the positions of four of its
      bases are not tightly constrained, while the remaining two are hydrogen-bonded
      [Laing, L. G., and Hall, K. B. (1996) Biochemistry 35, 13586]. To investigate the
      flexibility of the RNA in the loop and in the stem, 13C NMR relaxation methods
      have been used to describe the dynamics of the purine bases. IRE hairpins
      containing [13C]guanosine and [13C]adenosine are used in NMR experiments to
      measure T1, T1rho, and NOE values of the bases as a function of temperature (20
      37 degreesC). Data are analyzed using the Lipari-Szabo model-free formalism
      [Lipari, G., and Szabo, A. (1982) J. Am. Chem. Soc. 104, 4546] to determine order
      parameters and time scales of the motion. Results indicate that the purine bases
      in the stem have order parameters that are independent of temperature, although
      they show evidence of both fast (6-40 ps) motions and slower motions at 37
      degreesC. The three purines in the loop exhibit increasingly complex motions with
      long (nanoseconds) correlation times as the temperature increases, suggesting
      that the loop structure has become disordered.

PMID- 9649314
TI  - Influence of lipid/peptide hydrophobic mismatch on the thickness of
      diacylphosphatidylcholine bilayers. A 2H NMR and ESR study using designed
      transmembrane alpha-helical peptides and gramicidin A.
AB  - We have investigated the effect of a series of hydrophobic polypeptides (WALP
      peptides) on the mean hydrophobic thickness of (chain-perdeuterated)
      phosphatidylcholines (PCs) with different acyl chain length, using 2H NMR and ESR
      techniques. The WALP peptides are uncharged and consist of a sequence with
      variable length of alternating leucine and alanine, flanked on both sides by two
      tryptophans, and with the N- and C-termini blocked, e.g., FmAW2(LA)nW2AEtn. 2H
      NMR measurements showed that the shortest peptide with a total length of 16 amino
      acids (WALP16) causes an increase of 0.6 A in bilayer thickness in di-C12-PC, a
      smaller increase in di-C14-PC, no effect in di-C16-PC, and a decrease of 0.4 A in
      di-C18-PC, which was the largest decrease observed in any of the peptide/lipid
      systems. The longest peptide, WALP19, in di-C12-PC caused the largest increase in
      thickness of the series (+1.4 A), which decreased again for longer lipids toward
      di-C18-PC, in which no effect was noticed. WALP17 displayed an influence
      intermediate between that of WALP16 and WALP19. Altogether, incorporation of the
      WALP peptides was found to result in small but very systematic changes in bilayer
      thickness and area per lipid molecule, depending on the difference in hydrophobic
      length between the peptide and the lipid bilayer in the liquid-crystalline phase.
      ESR measurements with spin-labeled lipid probes confirmed this result. Because
      thickness is expected to be influenced most at the lipids directly adjacent to
      the peptides, also the maximal adaptation of these first-shell lipids was
      estimated. The calculation was based on the assumption that there is little or no
      aggregation of the WALP peptides, as was supported by ESR, and that lipid
      exchange is rapid on the 2H NMR time scale. It was found that even the maximal
      possible changes in first-shell lipid length were relatively small and
      represented only a partial response to mismatch. The synthetic WALP peptides are
      structurally related to the gramicidin channel, which was therefore used for
      comparison. In most lipid systems, gramicidin proved to be a stronger perturber
      of bilayer thickness than WALP19, although its length should approximate that of
      the shorter WALP16. The effects of gramicidin and WALP peptides on bilayer
      thickness were evaluated with respect to previous 31P NMR studies on the effects
      of these peptides on macroscopic lipid phase behavior. Both approaches indicate
      that, in addition to the effective hydrophobic length, also the physical nature
      of the peptide surface is a modulator of lipid order.

PMID- 9649315
TI  - Effect of N-terminal truncation and solution conditions on chemokine dimer
      stability: nuclear magnetic resonance structural analysis of macrophage
      inflammatory protein 1 beta mutants.
AB  - Chemokines (chemotactic cytokines) are a family of immune system proteins,
      several of which have been shown to block human immunodeficiency virus (HIV)
      infection in various cell types. While the solved structures of most chemokines
      reveal protein dimers, evidence has accumulated for the biological activity of
      individual chemokine monomers, and a debate has arisen regarding the biological
      role of the chemokine dimer. Concurrent with this debate, several N-terminal
      truncations and modifications in the CC subfamily of chemokines have been shown
      to have functional significance, in many cases antagonizing their respective
      receptors and in some cases retaining the ability to block HIV entry to the cell.
      As the dimer interface of CC chemokines is located at their N-terminus, a
      structural study of N-terminally truncated chemokines will address the effect
      that this type of mutation has on the dimer-monomer equilibrium. We have studied
      the structural consequences of N-terminal truncation in macrophage inflammatory
      protein 1 beta (MIP-1 beta), a CC chemokine that has been shown to block HIV
      infection. Examination of nuclear magnetic resonance (NMR) spectra of a series of
      N-terminally truncated MIP-1 beta variants reveals that these proteins possess a
      range of ability to dimerize. A mutant beginning at amino acid Asp6 [termed
      MIP(6)] has near wild-type dimer properties, while further truncation results in
      weakened dimer affinity. The mutant MIP(9) (beginning with amino acid Thr9) has
      been found to exist solely as a folded monomer. Relaxation measurements yield a
      rotational correlation time of 8.6 +/- 0.1 ns for wild-type MIP-1 beta and 4.5 +/
      0.1 ns for the MIP(9) mutant, consistent with a wild-type dimer and a fully
      monomeric MIP(9) variant. The presence of physiological salt concentration
      drastically changes the monomer-dimer equilibrium for both wild-type and most
      mutant proteins, heavily favoring the dimeric form of the protein. These results
      have implications for structure-function analysis of existing chemokine mutants
      as well as for the larger debate regarding the biological existence and activity
      of the chemokine dimer.

PMID- 9649316
TI  - Contribution of hydrogen bonds to the conformational stability of human lysozyme:
      calorimetry and X-ray analysis of six tyrosine --> phenylalanine mutants.
AB  - The contribution of hydrogen bonds to the conformational stability of human
      lysozyme was investigated by the combination of calorimetric and X-ray analyses
      of six Tyr --> Phe mutants. Unfolding Delta G and unfolding Delta H values of the
      Tyr --> Phe mutant proteins were changed by from +0.3 to -4.0 kJ/mol and from 0
      to -16 kJ/mol, respectively, compared to those of the wild-type protein. The net
      contribution of a hydrogen bond at a specific site to stability (Delta Gwild/HB),
      considering factors affected by substitutions, was evaluated on the basis of X
      ray structures of the mutant proteins. In the present study, one of six mutant
      proteins was suitable for evaluating the strength of the hydrogen bond. Delta
      Gwild/HB for the intramolecular hydrogen bond at Tyr124 was evaluated to be 7.5
      kJ/mol. Results of the analysis of other mutants also suggest that hydrogen bonds
      of the hydroxyl group of Tyr, including the hydrogen bond with a water molecule,
      contribute to the stabilization of the human lysozyme.

PMID- 9649317
TI  - Regulation of the expression or recruitment of components of the DNA synthesome
      by poly(ADP-ribose) polymerase.
AB  - Poly(ADP-ribose) polymerase (PARP) is a component of the multiprotein DNA
      replication complex (MRC, DNA synthesome) that catalyzes replication of viral DNA
      in vitro. PARP poly(ADP-ribosyl)ates 15 of the approximately 40 proteins of the
      MRC, including DNA polymerase alpha (DNA pol alpha), DNA topoisomerase I (topo
      I), and proliferating-cell nuclear antigen (PCNA). Although about equal amounts
      of MRC-complexed and free forms of PCNA were detected by immunoblot analysis of
      HeLa cell extracts, only the complexed form was poly(ADP-ribosyl)ated, suggesting
      that poly(ADP-ribosyl)ation of PCNA may regulate its function within the MRC. NAD
      inhibited the activity of DNA pol delta in the MRC in a dose-dependent manner,
      whereas the PARP inhibitor, 3-AB, reversed this inhibitory effect. The roles of
      PARP in modulating the composition and enzyme activities of the DNA synthesome
      were further investigated by characterizing the complex purified from 3T3-L1
      cells before and 24 h after induction of a round of DNA replication required for
      differentiation of these cells; at the latter time point, approximately 95% of
      the cells are in S phase and exhibit a transient peak of PARP expression. The MRC
      was also purified from similarly treated 3T3-L1 cells depleted of PARP by
      antisense RNA expression; these cells do not undergo DNA replication nor terminal
      differentiation. Both PARP protein and activity and essentially all of the DNA
      pol alpha and delta activities exclusively cosedimented with the MRC fractions
      from S phase control cells, and were not detected in the MRC fractions from PARP
      antisense or uninduced control cells. Immunoblot analysis further revealed that,
      although PCNA and topo I were present in total extracts from both control and
      PARP-antisense cells, they were present in the MRC fraction only from induced
      control cells, indicating that PARP may play a role in their assembly into an
      active DNA synthesome. In contrast, expression of DNA pol alpha, DNA primase, and
      RPA was down-regulated in PARP-antisense cells, suggesting that PARP may be
      involved in the expression of these proteins. Depletion of PARP also prevented
      induction of the expression of the transcription factor E2F-1, which positively
      regulates transcription of the DNA pol alpha and PCNA genes; thus, PARP may be
      necessary for expression of these genes when quiescent cells are stimulated to
      proliferate.

PMID- 9649318
TI  - Chromium(III) decreases the fidelity of human DNA polymerase beta.
AB  - Certain particulate compounds of hexavalent chromium are well-known occupational
      and environmental human carcinogens. Hexavalent chromium primarily enters the
      cells and undergoes metabolic reduction; however, the ultimate trivalent
      oxidation state of chromium, Cr(III), predominates within the cell. DNA-bound
      Cr(III) has been previously shown to decrease the fidelity of replication in the
      M13 phage mutation assay. This study was done to understand how Cr(III), in the
      presence of physiological concentrations of magnesium, affects the kinetic
      parameters of steady-state DNA synthesis in vitro across site-specific O6
      methylguanine (m6dG) residues by DNA polymerase beta (pol beta). Cr(III) binds to
      the short oligomer templates in a dose-dependent manner and stimulates the
      activity of pol beta. Cr(III) stimulates the mutagenic incorporation of dTTP
      opposite m6dG more than the nonmutagenic incorporation of dCTP, and thereby
      Cr(III) further decreases the fidelity of DNA synthesis across m6dG by pol beta.
      In contrast, Cr(III) does not affect the fidelity of DNA synthesis across the
      normal template base, dG. Both the enhanced activity and the mutagenic lesion
      bypass in the presence of Cr(III) may be associated with Cr(III)-dependent
      stimulation of pol beta binding to DNA as reported here. This study shows some of
      the mechanisms by which mutagenic chromium affects DNA synthesis.

PMID- 9649319
TI  - Antisense binding enhanced by tertiary interactions: binding of phosphorothioate
      and N3'-->P5' phosphoramidate hexanucleotides to the catalytic core of a group I
      ribozyme from the mammalian pathogen Pneumocystis carinii.
AB  - Pneumocystis carinii is the most common lethal opportunistic pathogen infecting
      Acquired Immune Deficiency Syndrome (AIDS) patients, and more effective
      therapeutics for it are needed. P. carinii, but not humans, contain RNA self
      splicing group I introns, so these functionally important RNAs are potential anti
      fungal targets. In vitro, d(ATGACT), which mimics the 3' end of the 5' exon of a
      conserved ribosomal RNA group I intron from mouse-derived Pneumocystis carinii
      binds to a ribozyme that is a truncated form of this intron. The binding is about
      30,000 times tighter than expected for simple base-pairing because binding is
      enhanced by tertiary interactions. Here we report the effects of modifying the
      phosphodiester backbone of d(ATGACT) with phosphorothioate and of d(ATGAC)rU with
      N3'-->P5' phosphoramidate linkages. The enhancement of binding by tertiary
      interactions is not substantially decreased, and in some cases is increased when
      single Rp and Sp phosphorothioate substitutions are made, although overall
      binding is weaker by up to 6-fold. A mixture of 5' exon mimic isomers that each
      contain five phosphorothioate linkages binds to the ribozyme at least 14-fold
      less tightly than the corresponding phosphodiester mimic. In contrast, the 5'
      exon mimic with five internal N3'-->P5' phosphoramidate linkages binds 4-fold
      more tightly than d(ATGAC)rU. This increased binding is largely due to more
      favorable base-pairing, but tertiary interactions still enhance binding by more
      than 2, 000-fold. These results indicate that chemically modified, nuclease
      stable 5' exon mimics can act as antisense agents with binding enhanced by
      tertiary interactions (BETI). This strategy permits design of short antisense
      agents with high specificity.

PMID- 9649320
TI  - Circular substrates of the hammerhead ribozyme shift the internal equilibrium
      further toward cleavage.
AB  - To test whether the Y-shaped conformation of the hammerhead ribozyme is
      maintained throughout the catalytic pathway, the cleavage properties of circular
      substrates which bind the ribozyme through helices I and II were determined.
      Constraining the position of helices I and II in this manner did not
      significantly alter the rate constant for cleavage, consistent with no large
      rearrangement of the helices occurring during catalysis. Unexpectedly, the
      "internal" equilibrium between the cleavage and ligation reactions for the
      circular hammerheads was shifted further toward cleavage. This effect was due to
      the rate of ligation of the circular substrate being slower than the
      corresponding linear substrate. The temperature dependence of the internal
      equilibrium of the circular substrate revealed that although restricting the
      flexibility of the hammerhead reduced the favorable entropy change associated
      with cleavage as expected, the unfavorable enthalpy change was reduced as well,
      resulting in greater overall cleavage.

PMID- 9649321
TI  - Shiga toxin attacks bacterial ribosomes as effectively as eucaryotic ribosomes.
AB  - Several pathogenic bacteria, including Shigelladysenteriae and certain strains of
      Escherichia coli, produce potent class 2 ribosome inhibiting proteins (RIPs)
      termed Shiga toxins (Stx). The toxins are bipartite molecules composed of a
      single A chain (StxA) noncovalently associated with a pentamer of receptor
      binding B subunits (StxB). StxA and Stx1A from E. coli are protoxins. Proteolysis
      generates an A1 enzyme (28 kDa) and an A2 fragment (3 kDa), which remain bound,
      inactivating the enzyme, until a disulfide bond linking them is reduced. Efforts
      to express active recombinant Stx1A1 in the cytoplasm of E. coli were very
      difficult and led to the hypothesis that Stx1A1 is toxic to E. coli. We created
      the gene for a His-tagged Stx1A1 (cStx1A1) and expressed it in E. coli from a
      tightly controlled expression vector. About 1-2 mg of protein can be purified in
      a one-step isolation from 1 L of culture. cStx1A1, RTA, and PAP exhibited similar
      high toxicity against the Artemia ribosomes with IC50 values near 1 nM.
      Surprisingly, Stx1A1 had an IC50 of 0.8 nM against E. coli ribosomes, about the
      same as it had for Artemia ribosomes. This is about 250 times more active than
      PAP against bacterial targets, making Stx1A1 the most powerful RIP toxin
      presently known against E. coli ribosomes.

PMID- 9649322
TI  - Differential effects of camptothecin derivatives on topoisomerase I-mediated DNA
      structure modification.
AB  - The effects of eleven camptothecin derivatives on calf thymus topoisomerase I
      mediated cleavage of synthetic DNA duplex have revealed that the A ring of
      camptothecin is very important for its biochemical activity. Depending on the
      type, number, and location of substituents, highly active or inactive analogues
      were obtained. The persistence of CPT-induced topoisomerase I-DNA covalent binary
      complexes was investigated by using as substrates DNA containing several good
      topoisomerase I cleavage sites, or else a synthetic DNA duplex of defined
      structure with a single high-efficiency cleavage site. The ligation kinetics at a
      given topoisomerase I cleavage site were sometimes quite different in the
      presence of CPT derivatives whose structures were closely related. Even in the
      presence of a single CPT analogue, topoisomerase I-DNA covalent binary complexes
      underwent ligation with different kinetics, presumably reflecting a dependence on
      DNA sequences flanking the individual topoisomerase I cleavage sites. Individual
      camptothecin derivatives also exhibited a spectrum of inhibitory potentials in
      blocking the topoisomerase I-mediated rearrangement of branched, nicked, and
      gapped DNA duplex substrates; in some cases the potencies of inhibition observed
      in these assays for individual camptothecin analogues were quite different than
      those determined for stabilization of the unmodified DNA-topoisomerase I binary
      complex.

PMID- 9649323
TI  - The protein component of Bacillus subtilis ribonuclease P increases catalytic
      efficiency by enhancing interactions with the 5' leader sequence of pre-tRNAAsp.
AB  - Ribonuclease P (RNase P) is a ribonucleoprotein complex that catalyzes the
      formation of the mature 5' end of tRNA. To investigate the role of the protein
      component in enhancing the affinity of Bacillus subtilis RNase P for substrate
      (Kurz, J. C., Niranjanakumari, S., Fierke, C. A. (1998) Biochemistry 37, 2393),
      the kinetics and thermodynamics of binding and cleavage were analyzed for pre
      tRNAAsp substrates containing 5' leader sequences of varying lengths (1-33
      nucleotides). These data demonstrate that the cleavage rate constant catalyzed by
      the holoenzyme is not dependent on the leader length; however, the association
      rate constant for substrate binding to holoenzyme increases as the length of the
      leader increases, and this is reflected in enhanced substrate affinity of up to 4
      kcal/mol. In particular, the protein component of RNase P stabilizes interactions
      with nucleotides at -2 and -5 in the 5' leader sequence of the pre-tRNA
      substrate. A 1 nucleotide leader decreases substrate affinity >/=15-fold compared
      to tRNAAsp due to ground-state destabilization of the enzyme-substrate complex.
      This destabilization is overcome by increasing the length of the leader to 2
      nucleotides due to P RNA-pre-tRNA contacts that are stabilized by the P protein.
      The affinity of RNase P holoenzyme (but not RNA alone) for pre-tRNAAsp is further
      enhanced with a substrate containing a 5 nucleotide leader. These data indicate
      that novel direct or indirect interactions occur between the 5' leader sequence
      of pre-tRNAAsp and the protein component of RNase P.

PMID- 9649324
TI  - Hairpin-forming peptide nucleic acid oligomers.
AB  - A series of partially self-complementary peptide nucleic acid (PNA) oligomers was
      prepared. Examination of their melting behavior, circular dichroism spectra, and
      fluorescence properties reveals that these PNA oligomers exist as stem-loop
      ("hairpin") structures. Fluorescence is readily observed in hairpins containing a
      covalently linked, emissive acridine derivative which is, at least partially,
      intercalated in the duplex region of the PNA hairpin. The acridine fluorescence
      is quenched when an anthraquinone derivative is covalently attached to the PNA so
      that it is bound near the acridine in the hairpin structure. Acridine
      fluorescence is restored in hairpins containing both the anthraquinone and the
      acridine by increasing the temperature and melting the structure to its linear
      form or by opening the hairpin through formation of a hybrid duplex with
      complementary DNA. The latter process may form the basis for development of
      selective and sensitive DNA assays.

PMID- 9649325
TI  - Influence of hairpins on template reannealing at trinucleotide repeat duplexes: a
      model for slipped DNA.
AB  - Hairpin stabilization of polymerase slippage has been proposed as part of the
      mechanism for large-scale expansion of CG-rich (CNG, where N = A, T, G, or C)
      trinucleotide repeats. However, hairpin formation does not entirely account for
      why long repeats but not short repeats or palindromes expand. Using ultraviolet
      spectroscopic methods, we examine the thermodynamic and kinetic properties of
      repeating trinucleotides to evaluate their behavior at a slippage site. We find
      that CNG trinucleotide repeats associated with expansion form stable hairpins
      whether they are short (with as few as 10 repeats) or long. However, long
      repeating stretches exist as single strands up to 2 orders of magnitude longer
      than sequences with either short repeats or random DNA. Thus, long hairpins have
      long lifetimes even in the presence of their complementary strands and inhibit
      duplex reannealing at a slippage site. The kinetic properties explain why
      expansion occurs with high frequency at long repeats but not at short repeats or
      palindromes.

PMID- 9649326
TI  - Nearest-neighbor thermodynamics of internal A.C mismatches in DNA: sequence
      dependence and pH effects.
AB  - Thermodynamics of 27 oligonucleotides with internal A.C mismatches at two
      different pHs were determined from UV absorbance versus temperature melting
      profiles. The data were combined with four literature values and used to derive
      nearest-neighbor parameters for all 16 trimer sequences with internal A.C
      mismatches at pH 7.0 and 5. 0. The results indicate that the contribution of
      single A.C mismatches to duplex stability is strongly dependent on the solution
      pH and the nearest-neighbor context. On average, the protonation of an internal
      A.C mismatch stabilizes the duplex by 1.39 kcal/mol for DeltaG degrees37 and 7.0
      degreesC for the TM. The nearest-neighbor parameters predict DeltaG degrees37,
      DeltaH degrees, DeltaS degrees, and TM of oligonucleotides presented in this
      study with average deviations of 6.3%, 11.0%, 12.2%, and 1.8 degreesC,
      respectively, at pH 7.0 and 4.7%, 5.9%, 6.1%, and 1.3 degreesC, respectively, at
      pH 5. 0. At pH 7.0, the contribution of single A.C mismatches to helix stability
      ranges from 2.25 kcal/mol for TCA/AAT to 1.22 kcal/mol for GCG/CAC. At pH 5.0,
      however, the contribution of A+.C mismatches ranges from 1.09 kcal/mol for
      TCT/AAA to -0.43 kcal/mol for GCC/CAG. Implications of the results for
      replication fidelity and mismatch repair are discussed.

PMID- 9649327
TI  - Fourier transform infrared evidence against Asp beta 99 protonation in
      hemoglobin: nature of the Tyr alpha 42-Asp beta 99 quaternary H-bond.
AB  - The Tyr alpha 42-Asp beta 99 intersubunit H-bond stabilizes the T quaternary
      structure in hemoglobin (Hb) tetramers. We had proposed that Tyr alpha 42 acts as
      an acceptor in this H-bond, because the tyrosine Y8a/8b and Y7a' UVRR
      (ultraviolet resonance Raman) bands shift in directions opposite to those
      expected if tyrosine is an H-bond donor. If Asp beta 99 is the H-bond donor, then
      it must be protonated in the T state, and would be a previously unrecognized
      contributor to the Bohr effect. This implication was strengthened by the
      discovery that an R-minus-T difference FTIR (Fourier transform infrared) band at
      1693 cm-1, which might be a signal from protonated carboxylate, is missing in Hb
      Kempsey, a mutant in which Asp beta 99 is replaced by Asn. However, we now find
      that this FTIR signal is insensitive to 13C-labeling of the aspartate residues in
      Hb, and cannot arise from protonated Asp beta 99. There are no other difference
      signals in the 1700 cm-1 region at a sensitivity of one COOH group. We conclude
      that Asp beta 99 is not protonated, and that the anomalous UVRR shifts must arise
      from compensating polarization of the Tyr alpha 42 OH. Candidates for this
      compensation are the H-bond donated by the Asp beta 94 backbone NH, and the
      nearby positive charge of Arg beta 40.

PMID- 9649328
TI  - Investigation of CO binding and release from Mo-nitrogenase during catalytic
      turnover.
AB  - During enzymatic turnover in the presence of CO, Mo-nitrogenase has been shown to
      generate two different EPR signals termed lo-CO (PCO = 0.08 atm) and hi-CO (PCO =
      0.5 atm). When the formation of hi-CO is monitored under the conditions of very
      low electron flux, a 2 min lag is observed prior to the initial detection of the
      signal followed by a near-linear rate of formation during which the S = 3/2
      cofactor signal exhibits similar decay kinetics. Increasing the electron flux
      produces a significant increase in the rate of both the formation of hi-CO and
      the decay of the S = 3/2 cofactor. These results are interpreted in terms of a
      state of the enzyme (redox or structural) generated only during turnover which is
      needed to initially bind CO to the cofactor. Under high electron flux conditions,
      new EPR inflections are observed at g = 5.78, 5.15 and g = 1.95, 1.81 and
      tentatively assigned to S = 3/2 and 1/2 states of the CO-bound cofactor and 1
      equiv of oxidized P cluster, respectively. Sudden removal of CO from the
      environment results in the slow decay (>10 min) of both the hi-CO signal and CO
      inhibition of acetylene reduction activity. The use of ethylene glycol to quench
      enzymatic activity strongly inhibits the decay of hi-CO (in the presence of CO)
      and the subsequent decay of lo-CO (after removal of CO) but does not prevent the
      reversible interconversion hi-CO left and right arrow lo-CO + CO.

PMID- 9649329
TI  - Simulation of S2-state multiline EPR signal in oriented photosystem II membranes:
      structural implications for the manganese cluster in an oxygen-evolving complex.
AB  - High-quality angular-dependent spectra of multiline electron paramagnetic
      resonance (EPR) signals from the S2-state Mn cluster in a photosynthetic oxygen
      evolving complex (OEC) were obtained for partially oriented photosystem (PS) II
      membranes, and the magnetic structure of the Mn cluster has been studied by
      simulation analysis. The angular-dependent multiline spectra were simulated by
      taking into account the anisotropic properties of both hyperfine tensors of
      intrinsic Mn ions and g-tensor of the cluster in a tetranuclear model. The best
      fit parameters for the simulation indicate that (a) the oxidation state of the S2
      state Mn cluster is Mn(III, IV, IV, IV), (b) the electronic orbital configuration
      of the Mn(III) ion is (dpi)3[dz2(sigma))]1, (c) the effective g-tensor of the Mn
      cluster and the hyperfine tensor of the Mn(III) ion are axially symmetric, and
      their principal z-axes are nearly collinear each other, and (d) the z-axis of the
      dz2 orbital of the Mn(III) ion and the normal of the thylakoid membrane are at an
      angle of 50.1 +/- 1.8 degrees. The results are compatible with those of the
      oriented XAFS study [Mukerji, I., et al. (1994) Biochemistry 33, 9712-9721], and
      indicate that the O-O vector of the putative di-mu-oxo bridged Mn(III)-Mn(IV)
      dimer unit in the Mn cluster tilts by 43-56 degrees with respect to the normal of
      thylakoid membrane. A model of the arrangement of the di-mu-oxo bridged Mn(III)
      Mn(IV) unit with respect to the thylakoid membrane is proposed.

PMID- 9649330
TI  - Temperature dependence of forward and reverse electron transfer from A1-, the
      reduced secondary electron acceptor in photosystem I.
AB  - Electron-transfer reactions following the formation of P700(+)A1- have been
      studied in isolated Photosystem I complexes from Synechococcus elongatus between
      300 and 5 K by flash absorption spectroscopy. (1) In the range from 300 to 200 K,
      A1- is reoxidized by electron transfer to the iron-sulfur cluster FX. The rate
      slows down with decreasing temperature, corresponding to an activation energy of
      220 +/- 20 meV in this temperature range. Analyzing the temperature dependence of
      the rate in terms of nonadiabatic electron-transfer theory, one obtains a
      reorganization energy of about 1 eV and an edge-to-edge distance between A1 and
      FX of about 8 A assuming the same distance dependence of the electron-transfer
      rate as in purple bacterial reaction centers. (2) At temperatures below 150 K,
      different fractions of PS I complexes attributed to frozen conformational
      substates can be distinguished. A detailed analysis at 77 K gave the following
      results: (a) In about 45%, flash-induced electron transfer is limited to the
      formation and decay of the secondary pair P700(+)A1-. The charge recombination
      occurs with a t1/2 of about 170 micros. (b) In about 20%, the state P700(+)FX- is
      formed and recombines with complex kinetics (t1/2 = 5-100 ms). (c) In about 35%,
      irreversible formation of P700(+)FA- or P700(+)FB- is possible. (3) The
      transition from efficient forward electron transfer at higher temperatures to
      heterogeneous photochemistry at low temperatures has been investigated in
      different glass-forming solvents. The yield of forward electron transfer to the
      iron-sulfur clusters decreases in a narrow temperature interval. The temperature
      of the half-maximal effect varies between different solvents and appears to be
      correlated with their liquid to glass transition. It is proposed that
      reorganization processes in the surroundings of the reactants which are required
      for the stabilization of the charge-separated state become arrested near the
      glass transition. This freezing of protein motions and/or solvent reorganization
      may affect electron-transfer reactions through changes in the free-energy gap and
      the reorganization energy. (4) The rate of charge recombination between P700(+)
      and A1- increases slightly (about 1.5-fold) when the temperature is decreased
      from 300 to 5 K. This charge recombination characterized by a large driving force
      is much less influenced by the solvent properties than the forward electron
      transfer steps from A1- to FX and FA/B.

PMID- 9649331
TI  - Fusion between retinal rod outer segment membranes and model membranes: a role
      for photoreceptor peripherin/rds.
AB  - Peripherin/rds plays an essential role in the maintenance of photoreceptor rod
      cell disk membrane structure. The purification of this protein to homogeneity
      [Boesze-Battaglia, K., et al. (1997) Biochemistry 36, 6835-6846] has allowed us
      to characterize the functional role of peripherin/rds in the maintenance of rod
      outer segment (ROS) membrane fusion processes. Utilizing a cell-free fusion assay
      system, we report that the fusion of R18-labeled ROS plasma membrane (R18-PM)
      with disk membranes or peripherin/rds-enriched large unilammellar vesicles (LUVs)
      is inhibited upon trypsinolysis of peripherin/rds. To understand this phenomenon,
      we tested the ability of a series of overlapping synthetic C-terminal
      peripherin/rds peptides to mediate model membrane fusion. Within the 63 amino
      acid long region of the C-terminus, we identified a minimal 15 residue long amino
      acid sequence (PP-5), which is necessary to promote membrane fusion. PP-5 was
      able to inhibit R18-PM disk membrane fusion and promoted ANTS/DPX contents mixing
      in a pure vesicle system. This peptide (PP-5) promoted calcium-induced vesicle
      aggregation of phosphatidylethanolamine:phosphatidylserine LUVs. FTIR analysis
      confirmed the structural prediction of this peptide as alpha-helical. When
      modeled as an alpha-helix, this peptide is amphiphilic with a hydrophobicity
      index of 0.75 and a hydrophobic moment of 0.59. PP-5 has substantial biochemical
      and functional homology with other well-characterized membrane fusion proteins.
      These results demonstrate the necessity for peripherin/rds in ROS membrane
      fusion, specifically the requirement for an intact C-terminal region of this
      protein.

PMID- 9649332
TI  - Depth profiles of pulmonary surfactant protein B in phosphatidylcholine bilayers,
      studied by fluorescence and electron spin resonance spectroscopy.
AB  - Pulmonary surfactant-associated protein B (SP-B) has been isolated from porcine
      lungs and reconstituted in bilayers of dipalmitoylphosphatidylcholine (DPPC) or
      egg yolk phosphatidylcholine (PC) to characterize the extent of insertion of the
      protein into phospholipid bilayers. The parameters for the interaction of SP-B
      with DPPC or PC using different reconstitution protocols have been estimated from
      the changes induced in the fluorescence emission spectrum of the single protein
      tryptophan. All the different reconstituted SP-B-phospholipid preparations
      studied had similar Kd values for the binding of the protein to the lipids, on
      the order of a few micromolar. The depth of penetration of SP-B into phospholipid
      bilayers has been estimated by the parallax method, which compares the relative
      efficiencies of quenching of the protein fluorescence by a shallow or a deeper
      spin-labeled phospholipid probe. SP-B tryptophan was found to be located 10-13 A
      from the center of bilayers, which is consistent with a superficial location of
      SP-B in phosphatidylcholine membranes. Parallax experiments, as well as resonance
      energy transfer from SP-B tryptophan to an acceptor probe located in the center
      of the bilayer, indicate that there are significant differences in the extent of
      insertion of the protein, depending on the method of reconstitution. SP-B
      reconstituted from lipid/protein mixtures in organic solvents is inserted more
      deeply in PC or DPPC bilayers than the protein reconstituted by addition to
      preformed phospholipid vesicles. These differences in the extent of insertion
      lead to qualitative and quantitative differences in the effect of the protein on
      the mobility of the phospholipid acyl chains, as studied by spin-label electron
      spin resonance (ESR) spectroscopy, and could represent different functional
      stages in the surfactant cycle.

PMID- 9649333
TI  - Nonesterified fatty acids induce transmembrane monovalent cation flux: host-guest
      interactions as determinants of fatty acid-induced ion transport.
AB  - Nonesterified fatty acids are key intermediates in cellular metabolism whose
      intracellular concentration is regulated by multiple anabolic, catabolic, and
      oxidative enzymatic cascades. Herein, we demonstrate that fatty acids induce
      transmembrane monovalent cation flux with an apparent rate constant kapp = 10(-)4
      - 10(-)3 s-1. Fatty acid-induced cation efflux exploits the ionic association of
      the cation with the carboxylate anion of the fatty acid and the subsequent
      transmembrane flip-flop of the fatty acid-cation complex. Rates of fatty acid
      induced transmembrane cation flux were dependent upon complex host-guest
      interactions between the fatty acid-cation complex and the phospholipid
      constituents which comprise the membrane bilayer including (1) the degree of
      unsaturation of the fatty acid guest and the regiospecificity and
      stereospecificity of its olefinic linkages; (2) the phospholipid subclass and
      individual molecular species which constitute the host membrane phospholipids;
      (3) impedance matching of host and guest hydrophobic characteristics; and (4) the
      cholesterol content of the membrane bilayer. Arrhenius analysis demonstrated that
      fatty acid-induced K+ efflux was facilitated largely by changes in the entropy of
      activation of ion translocation and not the energy of activation. Moreover,
      Arrhenius analysis demonstrated that the energy of activation of ion
      translocation was phospholipid subclass specific. For example, arachidonic acid
      induced cation efflux in membranes comprised of 16:0-18:1 plasmenylcholine
      possessed an Ea = 5.3 +/- 0.4 kcal/mol, while that for 16:0-18:1
      phosphatidylcholine was 7.2 +/- 0.5 kcal/mol. Electrophysiologic measurements of
      planar lipid membranes containing 10 mol % arachidonic acid as a substitutional
      impurity confirmed the ability of physiologically relevant amounts of fatty acid
      to induce ion translocation with a specific conductance of 2.6 +/- 0.3
      microS/cm2. Collectively, these results demonstrate that fatty acids facilitate
      transmembrane cation flux by an ion carrier type mechanism and suggest that fatty
      acid-mediated ion transport contributes to the leakage current present in many
      cell types and thus potentially modulates cellular responsivity during signal
      transduction where the intracellular content of fatty acids changes dramatically.

PMID- 9649334
TI  - Conformation and lipid binding properties of four peptides derived from the
      membrane-binding domain of CTP:phosphocholine cytidylyltransferase.
AB  - We are probing the mechanism of the lipid selective membrane interactions of
      CTP:phosphocholine cytidylyltransferase (CT). We have proposed that the membrane
      binding domain of CT (domain M) consists of a continuous amphipathic alpha-helix
      between residues approximately 240-295 [Dunne, S. J., et al. (1996) Biochemistry
      35, 11975-11984]. This study examined the secondary structure and membrane
      binding properties of synthetic peptides derived from domain M: a 62mer peptide
      encompassing the entire domain (Pep62), a 33mer corresponding to the N-terminal
      portion (PepNH1), and two 33mers corresponding to the three C-terminal 11mer
      repeats, one with the wild-type sequence (Pep33Ser), and one with the three
      serines in the nonpolar face substituted with alanine (Pep33Ala). Peptide
      secondary structure was analyzed by circular dichroism, and lipid interactions
      were analyzed by a direct vesicle binding assay, by effects of lipid vesicles on
      peptide tryptophan fluorescence, and by monolayer surface pressure changes. All
      peptides bound to vesicles as alpha-helices with selectivity for anionic lipids.
      Binding involved intercalation of the peptide tryptophan into the hydrophobic
      membrane core. PepNH1, the peptide with the highest positive charge density,
      showed strong selectivity for anionic lipids. PepNH1 and Pep33Ser did not bind to
      PC vesicles; however, the more hydrophobic peptides, Pep33Ala and Pep62, did bind
      to PC vesicles, with apparent partition coefficients for PC that were only
      approximately 1 order of magnitude lower than those for PC/PG (1/1). Our results
      suggest that the polar serines interrupting the nonpolar face of the amphipathic
      helix serve to lower the lipid affinity and thereby enhance selectivity for
      anionic lipids. Although diacylglycerol is an activator of the enzyme, none of
      the peptides responded differentially to PC/diacylglycerol vesicles versus pure
      PC vesicles, suggesting that domain M alone is not sufficient for the enzyme's
      response to diacylglycerol. Increases in surface pressure at an air-water
      interface indicated that the domain M peptides had strong surface-seeking
      tendencies. This supports a binding orientation for domain M parallel to the
      membrane surface. Binding of CT peptides to spread lipid monolayers caused
      surface pressure reductions, suggesting condensation of lipids in the formation
      of lipid-peptide complexes. At low monolayer surface pressures, Pep62 interacted
      equally with anionic and zwitterionic phospholipids. This suggests that one
      determinant of the selectivity for anionic lipids is the lipid packing density
      (area per molecule).

PMID- 9649335
TI  - Poly(ADP-ribose) modulates the properties of MARCKS proteins.
AB  - In mammalian cells, the formation of DNA strand breaks is accompanied by
      synthesis of poly(ADP-ribose). This nucleic acid-like homopolymer may modulate
      protein functions by covalent and/or noncovalent interactions. Here we show that
      poly(ADP-ribose) binds strongly to the proteins of the myristoylated alanine-rich
      C kinase substrate (MARCKS) family, MARCKS and MARCKS-related protein (also
      MacMARCKS or F52). MARCKS proteins are myristoylated proteins associated with
      membranes and the actin cytoskeleton. As targets for both protein kinase C (PKC)
      and calmodulin (CaM), MARCKS proteins are thought to mediate cross-talk between
      these two signal transduction pathways. Dot blot assays show that poly(ADP
      ribose) binds to MARCKS proteins at the highly basic effector domain. Complex
      formation between MARCKS-related protein and CaM as well as phosphorylation of
      MARCKS-related protein by the catalytic subunit of PKC are strongly inhibited by
      equimolar amounts of poly(ADP-ribose), suggesting a high affinity of poly(ADP
      ribose) for MARCKS-related protein. Binding of MARCKS-related protein to
      membranes is also inhibited by poly(ADP-ribose). Finally, poly(ADP-ribose)
      efficiently reverses the actin-filament bundling activity of a peptide
      corresponding to the effector domain and inhibits the formation of actin
      filaments in vitro. Our results suggest that MARCKS proteins and actin could be
      targets of the poly(ADP-ribose) DNA damage signal pathway.

PMID- 9649336
TI  - Evidence for hydrophobic interaction between galanin and the GalR1 galanin
      receptor and GalR1-mediated ligand internalization: fluorescent probing with a
      fluorescein-galanin.
AB  - Galanin is a neuropeptide that activates specific receptors to modulate several
      physiological functions including food intake, nociception, and learning and
      memory. The molecular nature of the interaction between galanin and its receptors
      and the fate of the galanin/receptor complex after the binding event are not
      understood. A fluorescein-N-galanin (F-Gal) was generated to measure the
      interaction between galanin and rat GalR1 galanin receptor (rGalR1) and rGalR1
      mediated ligand internalization using flow cytometry in transfected Chinese
      hamster ovary (CHO) cells. Like galanin, F-Gal bound rGalR1 with high affinity
      and stimulated intracellular signaling events. Fluorescence quenching by soluble
      KI of rGalR1-bound F-Gal revealed a highly protected environment around the
      fluorescein, suggesting that the N-terminal portion of galanin, which constitutes
      the binding site of galanin for the receptor, binds to a protected hydrophobic
      binding pocket within the receptor. Exposure to F-Gal stimulated rapid (t1/2
      approximately 10 min) and extensive (78%) internalization of surface F-Gal into
      rGalR1/CHO cells at 37 degreesC but not at 0 degreesC. In addition, the
      internalization did not occur in parental CHO cells at either 0 or 37 degreesC
      and was inhibited by addition of 0.25 M sucrose in the medium, indicating a GalR1
      mediated energy-requiring endocytic process. These results revealed a hydrophobic
      interaction between galanin and the GalR1 receptor, which is in contrast to those
      of other G protein-coupled receptors that mainly require hydrophilic interaction
      with their peptide ligands near or outside the plasma membrane surface, and
      illustrated that the initial binding interaction is followed by rapid cellular
      internalization of the agonist/GalR1 complex.

PMID- 9649337
TI  - Progressive decline in the ability of calmodulin isolated from aged brain to
      activate the plasma membrane Ca-ATPase.
AB  - To identify possible relationships between the loss of calcium homeostasis in
      brain associated with aging and alterations in the function of key calcium
      regulatory proteins, we have purified calmodulin (CaM) from the brains of Fischer
      344 rats of different ages and have assessed age-related alterations in (i) the
      secondary and tertiary structure of CaM and (ii) the ability of CaM to activate
      one of its target proteins, the plasma membrane (PM) Ca-ATPase. There is a
      progressive, age-dependent reduction in the ability of CaM to activate the PM-Ca
      ATPase, which correlates with the oxidative modification of multiple methionines
      to their corresponding methionine sulfoxides. No other detectable age-related
      posttranslational modifications occur in the primary sequence of CaM, suggesting
      that the reduced ability of CaM to activate the PM-Ca-ATPase is the result of
      methionine oxidation. Corresponding age-related changes in the secondary and
      tertiary structure of CaM occur, resulting in alterations in the relative
      mobility of CaM on polyacrylamide gels, differences in the intrinsic fluorescence
      intensity and solvent accessibility of Tyr99 and Tyr138, and a reduction in the
      average alpha-helical content of CaM at 20 degreesC. Shifts in the calcium- and
      CaM-dependent activation of the PM-Ca-ATPase are observed for CaM isolated from
      senescent brain, which respectively requires larger concentrations of either
      calcium or CaM to activate the PM-Ca-ATPase. The observation that the oxidative
      modification of CaM during normal biological aging results in a reduced calcium
      sensitivity of the PM-Ca-ATPase, a lower affinity between CaM and the PM-Ca
      ATPase, and the reduction in the maximal velocity of the PM-Ca-ATPase is
      consistent with earlier results that indicate the calcium handling capacity of a
      range of tissues including brain, heart, and erythrocytes isolated from aged
      animals declines, resulting in both longer calcium transients and elevated basal
      levels of intracellular calcium. Thus, the oxidative modification of selected
      methionines in CaM may explain aspects of the loss of calcium homeostasis
      associated with the aging process.

PMID- 9649338
TI  - Cationic residues 53 and 56 control the anion-induced interfacial k*cat
      activation of pancreatic phospholipase A2.
AB  - Added NaCl or anionic amphiphiles increase the rate of hydrolysis of dispersions
      of zwitterionic phospholipid by pancreatic phospholipase A2 (PLA2). Two effects
      of the negative charge at the interface have been dissected: enhanced binding of
      the enzyme to the interface, and k*cat activation of the enzyme at the interface
      [Berg et al. (1997) Biochemistry 36, 14512-14530]. Results reported here show
      that the structural basis for the k*cat activation is predominantly through
      cationic K53 and K56 in bovine pancreatic PLA2 with the anionic interface. The
      maximum rate at saturating diheptanoylphosphatidylcholine micelles, VMapp, for
      WT, K56M, and K53M in 4 M NaCl is in the 800-1300 s-1 range. In contrast, VMapp
      at 0.1 M NaCl is considerably higher for K56M (400 s-1) and K53M (230 s-1)
      compared to the rate with WT (30 s-1) or K56E (45 s-1). The rate of hydrolysis of
      anionic dimyristoylphosphatidylmethanol vesicles is virtually the same with all
      these mutants (200-300 s-1) and it is not affected by added NaCl. The chemical
      step for the hydrolysis of anionic and zwitterionic substrates remains rate
      limiting in the presence or absence of added NaCl. A modest (approximately 10
      fold) effect of K56M substitution or of added NaCl is seen on the binding of the
      enzyme to the interface; however, the binding of the substrate or a substrate
      mimic to the active site of the enzyme at the interface is not affected by more
      than a factor of 2. Magnitudes of the primary rate and equilibrium parameters at
      the zwitterionic and anionic interfaces show that the effect of mutation or of
      added NaCl is primarily on k*cat at the zwitterionic interface. These results are
      interpreted in terms of a two-state model for the interfacial allosteric
      activation, where the enzyme-substrate complex at the zwitterionic interface
      becomes catalytically active only after the positive charge on cationic K56 and
      K53 has been removed by mutation or neutralized by anionic charges in the
      interface.

PMID- 9649339
TI  - Effects of single and double mutations in plastocyanin on the rate constant and
      activation parameters for the rearrangement gating the electron-transfer reaction
      between the triplet state of zinc cytochrome c and cupriplastocyanin.
AB  - The unimolecular rate constant for the photoinduced electron-transfer reaction
      3Zncyt/pc(II) --> Zncyt+/pc(I) within the electrostatic complex of zinc
      cytochrome c and spinach cupriplastocyanin is kF. We report the effects on kF of
      the following factors, all at pH 7.0: 12 single mutations on the plastocyanin
      surface (Leu12Asn, Leu12Glu, Leu12Lys, Asp42Asn, Asp42Lys, Glu43Asn, Glu59Gln,
      Glu59Lys, Glu60Gln, Glu60Lys, Gln88Glu, and Gln88Lys), the double mutation
      Glu59Lys/Glu60Gln, temperature (in the range 273.3-302.9 K), and solution
      viscosity (in the range 1. 00-116.0 cP) at 283.2 and 293.2 K. We also report the
      effects of the plastocyanin mutations on the association constant (Ka) and the
      corresponding free energy of association (DeltaGa) with zinc cytochrome c at
      298.2 K. Dependence of kF on temperature yielded the activation parameters
      DeltaH, DeltaS, and DeltaG. Dependence of kF on solution viscosity yielded the
      protein friction and confirmed the DeltaG values determined from the temperature
      dependence. The aforementioned intracomplex reaction is not a simple electron
      transfer reaction because donor-acceptor electronic coupling (HAB) and
      reorganizational energy (lambda), obtained by fitting of the temperature
      dependence of kF to the Marcus equation, deviate from the expectations based on
      precedents and because kF greatly depends on viscosity. This last dependence and
      the fact that certain mutations affect Ka but not kF are two lines of evidence
      against the mechanism in which the electron-transfer step is coupled with the
      faster, but thermodynamically unfavorable, rearrangement step. The electron
      transfer reaction is gated by the slower, and thus rate determining, structural
      rearrangement of the diprotein complex; the rate constant kF corresponds to this
      rearrangement. Isokinetic correlation of DeltaH and DeltaS parameters and
      Coulombic energies of the various configurations of the Zncyt/pc(II) complex
      consistently show that the rearrangement is a facile configurational fluctuation
      of the associated proteins, qualitatively the same process regardless of the
      mutations in plastocyanin. Correlation of kF with the orientation of the
      cupriplastocyanin dipole moment indicates that the reactive configuration of the
      diprotein complex involves the area near the residue 59, between the upper acidic
      cluster and the hydrophobic patch. Kinetic effects and noneffects of plastocyanin
      mutations show that the rearrangement from the initial (docking) configuration,
      which involves both acidic clusters, to the reactive configuration does not
      involve the lower acidic cluster and the hydrophobic patch but involves the upper
      acidic cluster and the area near the residue 88.

PMID- 9649340
TI  - Spectroscopic and magnetic studies of human ceruloplasmin: identification of a
      redox-inactive reduced Type 1 copper site.
AB  - Ceruloplasmin is unique among the multicopper oxidases in that in addition to the
      usual copper stoichiometry of one Type 1 copper site and a Type 2/Type 3
      trinuclear copper cluster, it contains two other Type 1 sites. This assignment of
      copper sites, based on copper quantitation, sequence alignment, and
      crystallography, is difficult to reconcile with the observed spectroscopy.
      Furthermore, some chemical or spectroscopic differences in ceruloplasmin have
      been reported depending on the method of purification. We have studied the
      resting (as isolated by a fast, one-step procedure) and peroxide-oxidized forms
      of human ceruloplasmin. Using a combination of X-ray absorption spectroscopy, a
      chemical assay, magnetic susceptibility, electron paramagnetic resonance
      spectroscopy, and absorption spectroscopy, we have determined that peroxide
      oxidized ceruloplasmin contains one permanently reduced Type 1 site. This site is
      shown to have a reduction potential of approximately 1.0 V. Thus, one of the
      additional Type 1 sites in ceruloplasmin cannot be catalytically relevant in the
      form of the enzyme studied. Furthermore, the resting form of the enzyme contains
      an additional reducing equivalent, which is distributed among the remaining five
      copper sites as expected from their relative potentials. This may indicate that
      the resting form of ceruloplasmin in plasma under aerobic conditions is a four
      electron oxidized form, which is consistent with its function in the four
      electron reduction of dioxygen to water.

PMID- 9649341
TI  - Ro 09-2210 exhibits potent anti-proliferative effects on activated T cells by
      selectively blocking MKK activity.
AB  - By using high throughput screening of microbial broths, we have identified a
      compound, designated Ro 09-2210, which is able to block anti-CD3 induced
      peripheral blood T cell activation with an IC50 = 40 nM. Ro 09-2210 was also able
      to block antigen-induced IL-2 secretion with an IC50 = 30 nM, but was
      considerably less potent at blocking Ca2+ flux stimulated by anti-CD3 treatment.
      To determine the mechanism of action of Ro 09-2210, we set up a transient
      expression system in Jurkat T cells using a variety of reporter gene constructs
      and showed effective inhibition of phorbol ester/ionomycin-induced NF-AT
      activation and anti-CD3 induced NF-AT with IC50 = 7.7 and 10 nM, respectively. Ro
      09-2210 was also able to inhibit phorbol ester/ionomycin-induced activation of
      AP1 with IC50 = <10 nM. We further showed that Ro 09-2210 was unable to inhibit c
      jun induced expression of AP1-dependent reporter constructs (IC50 > 500 nM), but
      was able to potently inhibit ras-induced AP1 activation (IC50 = 20 nM). This
      suggested that Ro 09-2210 was inhibiting an activator of AP-1 which was upstream
      of c-jun and downstream of ras signaling. To investigate further, we then
      purified a number of different kinases, including PKC, PhK, ZAP-70, ERK, and MEK
      1 (a MKK), and showed that Ro 09-2210 was a selective inhibitor of MEK1 in vitro
      (IC50 = 59 nM).

PMID- 9649342
TI  - Role of important hydrophobic amino acids in the interaction between the
      glucocorticoid receptor tau 1-core activation domain and target factors.
AB  - In this work, we determined how altered-function mutants affecting hydrophobic
      residues within the tau 1-core activation domain of the human glucocorticoid
      receptor (GR) influence its physical interaction with different target proteins
      of the transcriptional machinery. Screening of putative target proteins showed
      that the tau 1-core can interact with the C-terminal part of the CREB-binding
      protein (CBP). In addition, the previously identified interactions of the tau 1
      core with the TATA-binding protein (TBP) and the Ada2 adaptor protein were
      localized to the C- and N-terminal regions of these proteins, respectively. A
      panel of mutations within the tau 1-core that either decrease or increase
      activation potential was used to probe the interaction of the tau 1-core domain
      with TBP, Ada2, and CBP. We found that the pattern of effects caused by the
      mutations was similar for each of the interactions and that the effects on
      binding generally reflected effects on gene activation potential. Thus, the
      predominant effect of the mutations appears to influence a property of the tau 1
      core that is common to all three interactions, rather than properties that are
      differentially required by each of the target factor interactions, individually.
      Such a property could be the ability of the domain to adopt a folded conformation
      that is generally necessary for interaction with target factors. We have also
      shown that TBP, Ada2, and CBP can interact with both the tau 1-core and the GR
      ligand-binding domain, offering a possible mechanism for synergistic interaction
      between the tau 1-core and other receptor activation domains. However, other
      target proteins (e.g., RIP140, and SRC-1), which interact with the GR C terminus,
      did not show significant interactions with the tau 1-core under our conditions.

PMID- 9649343
TI  - Thermal denaturation of ribonuclease A characterized by water 17O and 2H magnetic
      relaxation dispersion.
AB  - Water oxygen-17 and deuteron nuclear magnetic relaxation dispersion (NMRD)
      measurements were used to characterize ribonuclease A (RNase A) in the course of
      thermal denaturation at pH 2 and 4. The structure and dynamics of the protein
      were probed by specific long-lived water molecules, by the short-lived surface
      hydration, and by labile side-chain hydrogens. The NMRD data show that native
      RNase A contains at least three water molecules with a mean residence time of 8
      ns at 27 degreesC and an activation enthalpy of ca. 40 kJ mol-1. These water
      molecules are identified with some or all of six ordered water molecules partly
      buried in surface pockets in the crystal structure of RNase A. The loss of the
      17O dispersion at higher temperatures demonstrates that, in the thermally
      denatured protein, these surface pockets are either not present or undergoing
      large structural fluctuations on a subnanosecond time scale. The relaxation
      dispersion step vanishes monotonically and essentially in concert with the CD
      denaturation curves, thus ruling out the existence of equilibrium intermediates
      with a substantial amount of non-native and long-lived hydration water. The NMRD
      data show that thermally denatured RNase A has a relatively compact but highly
      flexible structure. The global solvent exposure and the hydrodynamic volume of
      the denatured protein are much less than for maximally unfolded disulfide-intact
      RNase A. The NMRD data show that thermal denaturation is accompanied by a large
      reduction of the mean-square orientational order parameter of side-chain O-H
      bonds, implying that, in the denatured state, these side chains sample a wide
      distribution of conformational states on a subnanosecond time scale.

PMID- 9649344
TI  - Formulation-related problems associated with intravenous drug delivery.

PMID- 9649345
TI  - The impact of stereoisomerism in bioequivalence studies.

PMID- 9649346
TI  - Metabolism of amprenavir in liver microsomes: role of CYP3A4 inhibition for drug
      interactions.
AB  - Amprenavir (141W94, VX-478, KVX-478) is metabolized primarily by CYP3A4
      (cytochrome P450 3A4) in recombinant systems and human liver microsomes (HLM).
      The effects of ketoconazole, terfenadine, astemizole, rifampicin, methadone, and
      rifabutin upon amprenavir metabolism were examined in vitro using HLM.
      Ketoconazole, terfenadine, and astemizole were observed to inhibit amprenavir
      depletion, consistent with their known specificity for CYP3A4. The HIV protease
      inhibitors, indinavir, saquinavir, ritonavir, and nelfinavir, were included in
      incubations containing amprenavir to examine the interactions of HIV protease
      inhibitors in vitro. The order of amprenavir metabolism inhibition in human liver
      microsomes was observed to be: ritonavir > indinavir > nelfinavir > saquinavir.
      The Ki value for amprenavir-mediated inhibition of testosterone hydroxylation in
      human liver microsomes was found to be approximately 0.5 microM. Studies suggest
      that amprenavir inhibits CYP3A4 to a greater extent than saquinavir, and to a
      much lesser extent than ritonavir. Amprenavir, nelfinavir, and indinavir appear
      to inhibit CYP3A4 to a moderate extent, suggesting a selected number of
      coadministration restrictions.

PMID- 9649347
TI  - Investigation on fouling mechanisms for recombinant human growth hormone sterile
      filtration.
AB  - During sterile filtration of recombinant human growth hormone solutions, severe
      membrane fouling was experienced compared to other protein preparations of
      significantly higher molecular weights and concentrations. This phenomenon was
      attributed to rhGH aggregation/adsorption occurring in the filter pore. To better
      understand this phenomenon, we examined several possible fouling mechanisms: (1)
      pore constriction, (2) adsorption due to nonspecific binding between protein and
      the membrane, (3) shear-induced adsorption, (4) hydrophobic interface-induced
      aggregation/adsorption. The protein solutions were sterily filtered using 0.22 mm
      filters, and their filtration fluxes were monitored. Filtration on the capillary
      and the noncapillary filters suggested that constraints by pore constriction and
      tortuosity played only a limited role. Filtration using filters with different
      degrees of protein binding tendency suggested that nonspecific adsorption was
      insignificant. The shear stress acting on the protein during filtration was
      small. RhGH which was intentionally sheared in a high-speed concentrically
      rotating device did not aggravate fouling tendency, suggesting that the shear
      induced adsorption might not be the major fouling mechanism. The dynamic light
      scattering data showed a trace amount of rhGH aggregates always present in
      equilibrium with the hydrophobic (air-water and membrane-water) interface. These
      aggregates tended to be adsorbed to the membrane, and more aggregates were
      generated presumably due to the equilibrium between aggregates and protein
      monomers. This adsorption/aggregation process eventually fouled the membrane.
      When the hydrophobic interface was occupied by surfactant molecules, the
      equilibration kinetics ceased to generate aggregates, thereby minimizing membrane
      fouling. This study clarified the cause of such an unusual fouling phenomenon
      upon microfiltration.

PMID- 9649348
TI  - Morphine-3-glucuronide has a minor effect on morphine antinociception.
      Pharmacodynamic modeling.
AB  - The objective of this study was to quantify the influence of morphine-3
      glucuronide (M3G) on the morphine antinociceptive effect (ANE) and respiratory
      effects in the rat. Three groups of rats were pretreated with either saline or
      M3G at two different rates. Morphine infusion of 10 mg/h/kg (group A) or 20
      mg/h/kg (group B) was administered to each pretreatment group for 3 h. The ANE
      was measured by the electrical stimulation vocalization method, and blood gas
      parameters (pCO2, pO2, and pH) were assessed. Independent of pretreatment all
      groups displayed a concurrent increase in the ANE. The maximal effect diverged
      between pretreatments. Acute tolerance was observed, but no rebound effect was
      detected. To characterize the ANE, an effect compartment model and an indirect
      response model were selected, both capable of describing the observed features.
      In both models incorporation of M3G led to a better explanation of the data. On
      the basis of the parameters obtained in the fits, naturally occurring M3G would
      reduce the antinociceptive effect during a morphine infusion (plasma
      concentration 15 microM) by 15-20%. The exposure of M3G did not significantly
      change the respiratory response following the morphine treatment.

PMID- 9649349
TI  - Quantitation of tricyclic antidepressant drugs based on the formation of mixed
      aggregates with surfactants.
AB  - A new approach for the quantitation of drugs, based on the measurement of the
      critical micelle concentration of mixed surfactant-drug aggregates, is proposed.
      This methodology involves the photometric titration of drugs in an aqueous medium
      using a surfactant as titrant. The Coomassie Brilliant Blue G (CBBG) dye,
      negatively charged, is used as a photometric probe. The analytical applicability
      of this approach is demonstrated by quantifying tricyclic antidepressants (TCAs)
      such as imipramine, desimipramine, amitriptylin, and nortriptylin. Aggregates
      studied included TCA-sodium dodecyl sulfate (SDS) and TCA-Triton X-100 mixtures.
      Because of the opposite charge of TCAs and SDS, which causes strong synergistic
      effects in the mixture relative to the properties of their individual components,
      this anionic surfactant was selected for the quantitation of TCAs. Pharmaceutical
      preparations can be analyzed directly after dissolution of the samples in water
      or ethanol. The detection limit achieved for the studied drugs is about 0.12 mg L
      1, so the proposed method surpasses existing alternative photometric methods in
      sensitivity and features a detection limit similar to fluorimetric methods. The
      relative standard deviation for 0.8 mg L-1 of TCA is 2.6%.

PMID- 9649350
TI  - Calculation of the dimensions of drug-polymer devices based on diffusion
      parameters.
AB  - The release kinetics of a polymeric-controlled release device are determined by
      its geometry and dimensions. A method to calculate the required size and shape of
      diffusion-controlled dosage forms to achieve a particular release profile is
      presented. The diffusion parameters are determined for various drugs
      (theophylline, diltiazem hydrochloride and caffeine) with thin ethyl cellulose
      (EC) films, containing different plasticizers [dibutyl sebacate (DBS) and acetyl
      tributyl citrate (ATBC)]. Computer simulations are then used to predict the drug
      release kinetics from various dosage forms (e.g. microparticles and cylinders).
      The practical benefit of these simulations is to optimize the geometry and
      dimensions of a controlled release device without the need of experimental
      studies. To verify the theoretical predictions, the release kinetics of
      theophylline from EC/ATBC microparticles of different size have also been
      determined experimentally. Good agreement is found between theory and experiment,
      proving the validity of the presented method.

PMID- 9649351
TI  - Racemate and enantiomers of ketoprofen: phase diagram, thermodynamic studies,
      skin permeability, and use of chiral permeation enhancers.
AB  - The role of intrinsic and extrinsic factors on transport of a chiral drug through
      the skin was studied. Ketoprofen (KP) was chosen as a model chiral drug. A
      possible relationship between the melting characteristics and the flux values of
      S- and RS-KP was investigated. The potential use of chiral enhancers, menthol and
      linalool, was also investigated. Thermal analyses were carried out for individual
      enantiomers and the racemate of KP. The melting temperature of each enantiomer
      was 22 degreesC lower than that of the racemic compound. Peak temperatures from
      the melting endotherms were plotted as a function of enantiomeric composition to
      give the binary phase diagram. The phase diagram suggested the presence of a
      racemic compound, and it was verified by calculations of the liquidus curve in
      the dystectic region using reported methods. Powder X-ray diffraction studies
      also confirmed that the racemate of KP is a racemic compound. The permeability of
      individual enantiomers and the racemate of KP through mice skin was determined in
      vitro using side-by-side diffusion cells. Transfer of R- and S-KP from aqueous
      solutions of both the racemate and pure enantiomer showed no significant
      differences in the rates of permeation, indicating that the rate of transfer of
      KP across the mice skin from these solutions was independent of the
      stereochemistry of the drug. No evidence of racemization during the transfer
      process was observed. The permeation-enhancing ratio of linalool was higher, but
      not significant, than that of l-menthol. The predicted ratio of enantiomer to
      racemate flux through the skin by the MTMT concept (1. 97) is in close agreement
      with the experimentally determined ratio (1.79) across mouse skin.

PMID- 9649352
TI  - Pharmacokinetics of (R,S)-Albuterol after aerosol inhalation in healthy adult
      volunteers.
AB  - The pharmacokinetics of inhaled (R,S)-albuterol following pulmonary absorption
      were studied in healthy human subjects. Ten subjects (5 females and 5 males)
      inhaled two puffs (180 microg) of albuterol via a metered-dose inhaler and spacer
      device. All subjects were nonsmoking and had normal pulmonary function. Charcoal
      slurries were ingested to block gastrointestinal absorption of drug. Venous
      samples were obtained from each subject at thirteen time points from 0 through 12
      h post dose. (R,S)-Albuterol concentration in plasma was measured using a gas
      chromatography-mass spectrometry (GC-MS) assay. The plasma concentration-time
      profiles conformed to a two-compartment extravascular model with first-order
      absorption kinetics. The drug levels reached maximum in 12.6 +/- 2.2 (SD)
      minutes, which is in contrast with previous reports that maximum plasma
      concentrations occur within 2 to 4 h. The mean peak plasma level was 1469 +/- 410
      pg/mL. The mean half-life of distribution was 17.9 +/- 8.2 min. The mean half
      life of elimination was 4.4 +/- 1.5 h. Female subjects achieved peak
      concentration more rapidly than male subjects (10.4 vs 14.8 min, p = 0.01) and
      had a higher mean peak concentration (1778 vs 1159 pg/mL, p = 0.04).

PMID- 9649353
TI  - Relative quantities of catalytically active CYP 2C9 and 2C19 in human liver
      microsomes: application of the relative activity factor approach.
AB  - The relative catalytic activities of CYP2C9 and CYP2C19 in human liver microsomes
      has been determined using the approach of relative activity factors (RAFs).
      Tolbutamide methylhydroxylation and S-mephenytoin 4'-hydroxylation were used as
      measures of CYP2C9 and CYP2C19 activity, respectively. The kinetics of these
      reactions were studied in human liver microsomes, in microsomes from human
      lymphoblastoid cells, and in insect cells expressing CYP2C9 and CYP2C19. RAFs
      were calculated as the ratio of Vmax (reaction velocity at saturating substrate
      concentrations) in human liver microsomes of the isoform-specific index reaction
      divided by the Vmax of the reaction catalyzed by the cDNA expressed isoform. RAFs
      were also determined for SUPERMIX, a commercially available mixture of cDNA
      expressed human drug metabolizing CYPs formulated to achieve a balance of enzyme
      activities similar to that found in human liver microsomes. Lymphoblast RAF2C9 in
      human liver microsomes ranged from 54 to 145 pmol CYP/mg protein (mean value:
      87), while a value of 251 pmol CYP/mg protein was obtained for SUPERMIX. Insect
      cell RAF2C9 in human liver microsomes ranged from 1.6 to 143 pmol CYP/mg protein
      (mean value: 49), while a value of 201 pmol CYP/mg protein was obtained for
      SUPERMIX. Both lymphoblast and insect cell RAF2C19 in human liver microsomes
      ranged from 4 to 45 pmol CYP/mg protein (mean values: 29 and 28, respectively),
      while a value of 29 pmol CYP/mg protein was obtained for SUPERMIX. The nature of
      the cDNA expression system used had no effect on the kinetic parameters of CYP2C9
      as a tolbutamide methylhydroxylase, or of CYP2C19 as a S-mephenytoin hydroxylase.
      However insect cell expressed CYP2C19 (which includes oxidoreductase) had
      substantially greater activity as a tolbutamide methylhydroxylase when compared
      to lymphoblast expressed CYP2C19. The ratio of mean lymphoblast-determined RAF2C9
      to RAF2C19 in human livers was 3.0 (range 1.6-17.9; n = 10), while this ratio for
      SUPERMIX was 8.6. The ratio of mean insect cell-determined RAF2C9 to RAF2C19 in
      human livers was 1.7 (range 0.04-16.2; n = 10), while this ratio for SUPERMIX was
      7.0. Neither ratio is in agreement with the 20:1 ratio of immunoquantified levels
      of CYP2C9 and 2C19 in human liver microsomes reported in previous studies.
      SUPERMIX may contain catalytically active CYP2C9 in levels higher than those in
      human liver microsomes.

PMID- 9649354
TI  - Tachycardia alone fails to change the myocardial pharmacokinetics and dynamics of
      lidocaine, thiopental, and verapamil after intravenous bolus administration in
      sheep.
AB  - Previous reports have suggested that tachycardia alone can increase the rate of
      myocardial uptake of some drugs. As part of a systematic study of the
      determinants of the myocardial uptake and effects of drugs in critical illness,
      the effect of tachycardia induced by intracardiac pacing on the myocardial
      disposition and effects of lidocaine, verapamil, and thiopental were studied in
      chronically instrumented sheep. For each drug, seven sheep received either 100 mg
      of lidocaine, 10 mg of verapamil, or 750 mg of thiopental over 2 min in unpaced
      and paced (140 beats/min) states on separate occasions and in random order.
      Arterial and coronary sinus (effluent from the heart) blood samples were taken at
      regular intervals for 30 min, and the maximum rate of change of left ventricular
      pressure (LV dP/dtmax) was measured as an index of myocardial contractility.
      There were no differences between unpaced and paced studies in the time courses
      of arterial and coronary sinus concentrations, or the time-courses of myocardial
      contractility and blood flow, after bolus iv injections of these drugs.
      Tachycardia alone does not appear to influence the myocardial kinetics or
      dynamics of lipophilic drugs that can rapidly diffuse into the heart.

PMID- 9649355
TI  - Compositional heterogeneity in parenteral lipid emulsions after sedimentation
      field flow fractionation.
AB  - This study examines the size and compositional heterogeneity of particles in a
      commercial lipid emulsion (Intralipid) before and after equilibration with
      penclomedine, a highly lipophilic cytotoxic agent. Emulsions were fractionated by
      sedimentation field-flow fractionation (sedFFF), and particle sizes of the
      monodisperse fractions were determined by photon correlation spectroscopy. The
      triglyceride (TG), phosphatidylcholine (PC), and penclomedine (in drug loaded
      emulsions) contents in each fraction were determined by HPLC. The aqueous
      entrapped volume within Intralipid was determined to be approximately 10% by size
      exclusion chromatography using [3H]mannitol. Thirteen sedFFF fractions collected
      from the drug free emulsions yielded particles ranging in size from 154 to 423
      nm. Total channel recoveries were 89% and 95% for TG and PC, respectively.
      Apparent particle densities varied significantly with size, suggesting
      heterogeneity in composition as confirmed by PC/TG mass ratios which varied
      dramatically. Computer fits of the distribution profiles suggested populations of
      phospholipid vesicles and oil droplets containing excess phospholipid in addition
      to classical emulsion droplets. Drug loading induced a significant shift of the
      predominant triglyceride containing population to a larger particle size. The
      penclomedine distribution profile closely mimicked that of the TG rather than the
      PC fraction. These studies suggest the need to consider not only size
      distribution but also compositional distribution in characterizing parenteral
      emulsions.

PMID- 9649356
TI  - In vitro release evaluation of hydrocortisone liquisolid tablets.
AB  - The potential of liquisolid systems to improve the dissolution properties of
      water-insoluble agents was investigated using hydrocortisone as the model
      medication. The in vitro release patterns of this very slightly water-soluble
      corticosteroid, formulated in directly compressed tablets and liquisolid
      compacts, were studied at different dissolution conditions. The new formulation
      technique of liquisolid compacts was used to convert liquid medications such as
      solutions or suspensions of hydrocortisone in propylene glycol, a nonvolatile
      liquid vehicle, into acceptably flowing and compressible powders by blending with
      selective powder excipients. Several liquisolid tablet formulations were prepared
      using a new mathematical model to calculate the appropriate quantities of powder
      and liquid ingredients required to produce acceptably flowing and compressible
      admixtures. Due to their increased wetting properties and surface of drug
      available for dissolution, liquisolid compacts demonstrated significantly higher
      drug release rates than those of conventionally made, directly compressed tablets
      containing micronized hydrocortisone. The in vitro drug dissolution rates of
      liquisolid tablets were found to be consistent and independent of the volume of
      dissolution medium used, in contrast to the plain tablets which exhibited
      declining drug release patterns with decreasing dissolution volumes. It has been
      also shown that the fraction of molecularly dispersed drug in the liquid
      medication of liquisolid systems is directly proportional to their hydrocortisone
      dissolution rates.

PMID- 9649357
TI  - On mathematical modeling of dermal and transdermal drug delivery.
AB  - This paper deals with two extensions of diffusion models for the drug delivery
      process into human skin in order to give a more realistic approach. As one
      extension several penetrating substances formulated within a vehicle are
      considered for modeling the case of an applied drug and some penetration
      modifiers (enhancers and reducers, respectively). A coupling via concentration
      dependent diffusivities between the diffusion equations of the involved
      substances is used to model the dependencies between them. Furthermore, a moving
      boundary problem for the diffusion equation of the drug delivery process is
      developed to describe the time-dependent maximum penetration depth of each
      penetrant marked by a movingboundary. On this basis a model is developed that can
      predict both the concentration profile and the position of the penetration
      boundary depending on time. Both concepts are described on a two-dimensional
      multilayered domain representing a cross section through human skin. The model
      equations are solved by exploiting a suitable numerical discretization method.

PMID- 9649358
TI  - How an increase in the carbon chain length of the ester moiety affects the
      stability of a homologous series of oxprenolol esters in the presence of
      biological enzymes.
AB  - beta-Blockers including timolol and propranolol are administered in eye-drops for
      the treatment of glaucoma. Due to high incidence of cardiovascular and
      respiratory side-effects, their therapeutic value is limited. As a result of poor
      ocular bioavailability, many ocular drugs are applied in high concentrations,
      which give rise to both ocular and systemic side-effects. Therefore, some methods
      have been employed to increase ocular bioavailability such as (a) the development
      of drug delivery devices designed to release drugs at controlled rates, (b) the
      use of various vehicles that retard precorneal drug loss, and (c) the conversion
      of drugs to biologically reversible derivatives (prodrugs) with increased corneal
      penetration properties, from which the active drugs are released by enzymatic
      hydrolysis. A series of structurally related oxprenolol esters were synthesized
      and investigated as potential prodrugs for improved ocular use. The stability of
      each ester was studied in phosphate buffer (pH 7.4), also in the presence of (a)
      30% human plasma, (b) aqueous humor, and (c) corneal extract at pH 7. 4 and at 37
      degreesC. An account is given of how the stability of a homologous series of
      oxprenolol esters in the presence of biological enzymes is affected by an
      increase in the carbon chain length of the ester moiety.

PMID- 9649359
TI  - Determination of absorption characteristics of AG337, a novel thymidylate
      synthase inhibitor, using a perfused rat intestinal model.
AB  - The purpose of this study was to determine the intestinal absorption
      characteristics of AG337, a mechanism-based inhibitor of thymidylate synthase,
      using a perfused rat intestinal model. Effects of site, pH, temperature,
      concentration, Na+, and inhibitors on the absorption of AG337 were determined,
      after the compound was shown to be stable in buffers of various pH, blank
      perfusate, and intestinal homogenate. The results indicated that absorption of
      AG337 was temperature-, pH-, Na+-, concentration-, and site-dependent. The best
      site of absorption is duodenum, where the absorption was 3-10 times (p < 0. 05)
      higher than absorption at jejunum, ileum, and colon. Among the four pH's studied,
      the best was at pH 6.5 (p < 0.05). Absorption was 80% lower in the absence of
      Na+, and 75% lower when the temperature of the perfusate was decreased to 4
      degreesC. Permeability of AG337 also decreased about 75% when the concentration
      was raised to 100 microM. These results suggest that a nutrient carrier may be
      involved in the transport of AG337. To determine the carrier responsible for the
      absorption of AG337, its absorption was determined in the presence of various
      inhibitors at different concentrations. The results indicated that transport of
      AG337 was inhibited significantly (p < 0.01) by 100 microM of adenine,
      hypoxanthine, and xanthine. The transport was also inhibited significantly (p <
      0.01) by a mixture of 100 microM each of adenine, hypoxanthine, and xanthine, but
      not by a mixture of 100 microM each of thymine and uracil. A higher concentration
      of hypoxanthine resulted in increased inhibition. In contrast, prototypical
      inhibitors of nucleoside transporter, dipyridamole and nitrobenzylthioinosine
      (NBMPR), did not significantly decrease the transport of AG337. The results also
      showed that absorption of AG337 had a significant nonsaturable component, with a
      nonsaturable Pw of 0.8. In conclusion, absorption of AG337 in the rat intestine
      has been shown to be mainly via a purine base carrier with a significant
      nonsaturable component.

PMID- 9649360
TI  - Interactions of griseofulvin with cyclodextrins in solid binary systems.
AB  - Griseofulvin/cyclodextrin interactions were investigated in aqueous environment
      and in solid state. Two cyclodextrin derivatives (beta-cyclodextrin and 2
      hydroxypropyl beta-cyclodextrin) were used to prepare different physical mixtures
      and kneaded systems, and the drug/cyclodextrin ratios were 1:1 and 1:2 mol/mol.
      Scanning electron microscopy (SEM), hot-stage microscopy (HSM), differential
      scanning calorimetry (DSC), thermogravimetry (TG), and X-ray powder
      diffractometry were employed to characterize pure substances and their kneaded
      counterparts and all of the binary systems. The solubility of griseofulvin was
      increased in accord with the quantity of cyclodextrin added. HSM examination
      revealed that 2-hydroxypropyl-beta-cyclodextrin was dissolved in the droplets of
      melted griseofulvin, but did not show any interactions between melted
      griseofulvin and beta-cyclodextrin particles. The presence of griseofulvin
      endothermic peak in the DSC curves of all binary systems suggests the absence of
      any griseofulvin/cylcodextrin inclusion compound in the solid state. In TG, data
      of weight loss owing to the dehydration of cyclodextrins was similar for both
      kneaded systems and physical mixtures. X-ray diffraction patterns exhibited the
      amorphous nature of 2-hydroxypropyl-beta-cyclodextrin and the crystalline nature
      of griseofulvin and binary systems. Griseofulvin dissolution profiles from all
      binary systems showed an improvement in drug dissolution, which indicates that an
      "in situ" drug/cyclodextrin inclusion compound was formed in the aqueous
      dissolution medium.

PMID- 9649361
TI  - Plasma-pooling methods to increase throughput for in vivo pharmacokinetic
      screening.

PMID- 9649362
TI  - Splanchnic clearance and its relationship with drug elimination by the liver and
      gastrointestinal tract.

PMID- 9649363
TI  - Spiral waves in two-dimensional models of ventricular muscle: formation of a
      stationary core.
AB  - Previous experimental studies have clearly demonstrated the existence of drifting
      and stationary electrical spiral waves in cardiac muscle and their involvement in
      cardiac arrhythmias. Here we present results of a study of reentrant excitation
      in computer simulations based on a membrane model of the ventricular cell. We
      have explored in detail the parameter space of the model, using tools derived
      from previous numerical studies in excitation-dynamics models. We have found
      appropriate parametric conditions for sustained stable spiral wave dynamics (1 s
      of activity or approximately 10 rotations) in simulations of an anisotropic
      (ratio in velocity 4:1) cardiac sheet of 2 cm x 2 cm. Initially, we used a model
      that reproduced well the characteristics of planar electrical waves exhibited by
      thin sheets of sheep ventricular epicardial muscle during rapid pacing at a cycle
      length of 300 ms. Under these conditions, the refractory period was 147 ms; the
      action potential duration (APD) was 120 ms; the propagation velocity along fibers
      was 33 cm/s; and the wavelength along fibers was 4.85 cm. Using cross-field
      stimulation in this model, we obtained a stable self-sustaining spiral wave
      rotating around an unexcited core of 1.75 mm x 7 mm at a period of 115 ms, which
      reproduced well the experimental results. Thus the data demonstrate that stable
      spiral wave activity can occur in small cardiac sheets whose wavelength during
      planar wave excitation in the longitudinal direction is larger than the size of
      the sheet. Analysis of the mechanism of this observation demonstrates that,
      during rotating activity, the core exerts a strong electrotonic influence that
      effectively abbreviates APD (and thus wavelength) in its immediate surroundings
      and is responsible for the stabilization and perpetuation of the activity. We
      conclude that appropriate adjustments in the kinetics of the activation front
      (i.e., threshold for activation and upstroke velocity of the initiating beat) of
      currently available models of the cardiac cell allow accurate reproduction of
      experimentally observed self-sustaining spiral wave activity. As such, the
      results set the stage for an understanding of functional reentry in terms of
      ionic mechanisms.

PMID- 9649364
TI  - A simple numerical model of calcium spark formation and detection in cardiac
      myocytes.
AB  - The elementary events of excitation-contraction coupling in heart muscle are Ca2+
      sparks, which arise from one or more ryanodine receptors in the sarcoplasmic
      reticulum (SR). Here a simple numerical model is constructed to explore Ca2+
      spark formation, detection, and interpretation in cardiac myocytes. This model
      includes Ca2+ release, cytosolic diffusion, resequestration by SR Ca2+-ATPases,
      and the association and dissociation of Ca2+ with endogenous Ca2+-binding sites
      and a diffusible indicator dye (fluo-3). Simulations in a homogeneous, isotropic
      cytosol reproduce the brightness and the time course of a typical cardiac Ca2+
      spark, but underestimate its spatial size (approximately 1.1 micron vs.
      approximately 2.0 micron). Back-calculating [Ca2+]i by assuming equilibrium with
      indicator fails to provide a good estimate of the free Ca2+ concentration even
      when using blur-free fluorescence data. A parameter sensitivity study reveals
      that the mobility, kinetics, and concentration of the indicator are essential
      determinants of the shape of Ca2+ sparks, whereas the stationary buffers and
      pumps are less influential. Using a geometrically more complex version of the
      model, we show that the asymmetric shape of Ca2+ sparks is better explained by
      anisotropic diffusion of Ca2+ ions and indicator dye rather than by subsarcomeric
      inhomogeneities of the Ca2+ buffer and transport system. In addition, we examine
      the contribution of off-center confocal sampling to the variance of spark
      statistics.

PMID- 9649365
TI  - Free energy profiles for H+ conduction along hydrogen-bonded chains of water
      molecules.
AB  - The molecular mechanism for proton conduction along hydrogen-bonded chains, or
      "proton wires," is studied with free energy simulations. The complete transport
      of a charge along a proton wire requires two complementary processes: 1)
      translocation of an excess proton (propagation of an ionic defect), and 2)
      reorientation of the hydrogen-bonded chain (propagation of a bonding defect). The
      potential of mean force profile for these two steps is computed in model systems
      comprising a single-file chain of nine dissociable and polarizable water
      molecules represented by the PM6 model of Stillinger and co-workers. Results of
      molecular dynamics simulations with umbrella sampling indicate that the
      unprotonated chain is preferably polarized, and that the inversion of its total
      dipole moment involves an activation free energy of 8 kcal/mol. In contrast, the
      rapid translocation of an excess H+ across a chain extending between two
      spherical solvent droplets is an activationless process. These results suggest
      that the propagation of a bonding defect constitutes a limiting step for the
      passage of several protons along single-file chains of water molecules, whereas
      the ionic translocation may be fast enough to occur within the lifetime of
      transient hydrogen-bonded water chains in biological membranes.

PMID- 9649366
TI  - Structure of the Ca2+ pump of sarcoplasmic reticulum: a view along the lipid
      bilayer at 9-A resolution.
AB  - We have used multilamellar crystals of the ATP-driven calcium pump from
      sarcoplasmic reticulum to address the structural effects of calcium binding to
      the enzyme. They are stacks of disk-shaped two-dimensional crystals. A density
      map projected along the lipid bilayer was obtained at 9-A resolution by frozen
      hydrated electron microscopy. Although only in projection, much more details of
      the structure were revealed than previously available, especially in the
      transmembrane region. Quantitative comparison was made with the model obtained
      from the tubular crystals of this enzyme formed in the absence of calcium.
      Unexpectedly large differences in conformation were found, particularly in the
      cytoplasmic domain.

PMID- 9649367
TI  - Capacitance flickers and pseudoflickers of small granules, measured in the cell
      attached configuration.
AB  - We have studied exocytosis of single small granules from human neutrophils by
      capacitance recordings in the cell-attached configuration. We found that 2.2% of
      the exocytotic events were flickers. The flickers always ended with a downward
      step. This indicates closing of the fusion pore. During flickering, the fusion
      pore conductance remained below 1 nS, and no net membrane transfer was
      detectable. After fusion pore expansion beyond 1 nS the pore expanded
      irreversibly, leading to rapid full incorporation of the granule/vesicle into the
      plasma membrane. Following exocytosis of single granules, a capacitance decrease
      directly related to the preceding increase was observed in 7% of the exocytotic
      events. This decrease followed immediately after irreversible pore expansion, and
      is presumably triggered by full incorporation of the vesicle into the patch
      membrane. The capacitance decrease could be interpreted as endocytosis triggered
      by exocytosis. However, the gradual decrease could also reflect a decrease in the
      "free" patch area following incorporation of an exocytosed vesicle. We conclude
      that non-stepwise capacitance changes must be interpreted with caution, since a
      number of factors go into determining cell or patch admittance.

PMID- 9649368
TI  - Simulating energy flow in biomolecules: application to tuna cytochrome c.
AB  - By constructing a continuity equation of energy flow, one can utilize results
      from a molecular dynamics simulation to calculate the energy flux or flow in
      different parts of a biomolecule. Such calculations can yield useful insights
      into the pathways of energy flow in biomolecules. The method was first tested on
      a small system of a cluster of 13 argon atoms and then applied to the study of
      the pathways of energy flow after a tuna ferrocytochrome c molecule was oxidized.
      Initially, energy propagated faster along the direction perpendicular to the heme
      plane. This was due to an efficient through-bond mechanism, because the heme iron
      in cytochrome c was covalently bonded to a cysteine and a histidine. For the
      oxidation of cytochrome c, electrostatic interactions also facilitated a long
      range through-space mechanism of energy flow. As a result, polar or charged
      groups that were further away from the oxidation site could receive energy
      earlier than nonpolar groups closer to the site. Another bridging mechanism
      facilitating efficient long-range responses to cytochrome c oxidation involved
      the coupling of far-off atoms with atoms that were nearer to, and interacted
      directly with, the oxidation site. The different characteristics of these energy
      transfer mechanisms defied a simple correlation between the time that the excess
      energy of the oxidation site first dissipated to an atom and the distance of the
      atom from the oxidation site. For tuna cytochrome c, all of the atoms of the
      protein had sensed the effects of the oxidation within approximately 40 fs. For
      the length scale of energy transfer considered in this study, the speed of the
      energy propagation in the protein was on the order of 10(5) m/s.

PMID- 9649369
TI  - Stability of triple-helical poly(dT)-poly(dA)-poly(dT) DNA with counterions.
AB  - Structural conformation of triple-helical poly(dT)-poly(dA)-poly(dT) has been a
      very controversial issue recently. Earlier investigations, based on fiber
      diffraction data and molecular modeling, indicated an A-form conformation with
      C'3-endo sugar pucker. On the other hand, Raman, solution infrared spectral, and
      NMR studies show a B-form structure with C'2-endo sugars. In accordance with
      these experimental results, a theoretical model with B-form, C'2-endo sugars was
      proposed in 1993. In the present work we investigate the dynamics and stability
      of the two conformations within the effective local field approach applied to the
      normal mode calculations for the system. The presence of counterions was
      explicitly taken into account. Stable equilibrium positions for the counterions
      were calculated by analyzing the normal mode dynamics and free energy of the
      system. The breathing modes of the triple helix are shifted to higher frequencies
      over those of the double helix by 4-16 cm-1. The characteristic marker band for
      the B conformation at 835 cm-1 is split up into two marker bands at 830 and 835
      cm-1. A detailed comparison of the normal modes and the free energies indicates
      that the B-form structure, with C'2-endo sugar pucker, is more stable than the A
      form structure. The normal modes and the corresponding dipole moments are found
      to be in close agreement with recent spectroscopic findings.

PMID- 9649370
TI  - Computer simulations of de novo designed helical proteins.
AB  - In the context of reduced protein models, Monte Carlo simulations of three de
      novo designed helical proteins (four-member helical bundle) were performed. At
      low temperatures, for all proteins under consideration, protein-like folds having
      different topologies were obtained from random starting conformations. These
      simulations are consistent with experimental evidence indicating that these de
      novo designed proteins have the features of a molten globule state. The results
      of Monte Carlo simulations suggest that these molecules adopt four-helix bundle
      topologies. They also give insight into the possible mechanism of folding and
      association, which occurs in these simulations by on-site assembly of the
      helices. The low-temperature conformations of all three sequences have the
      features of a molten globule state.

PMID- 9649371
TI  - Physical constraints in the synthesis of glycogen that influence its structural
      homogeneity: a two-dimensional approach.
AB  - Several aspects of glycogen optimization as an efficient fuel storage molecule
      have been studied in previous works: the chain length and the branching degree.
      These results demonstrated that the values of these variables in the cellular
      molecule are those that optimize the structure-function relationship. In the
      present work we show that structural homogeneity of the glycogen molecule is also
      an optimized variable that plays an important role in its metabolic function.
      This problem was studied by means of a two-dimensional approach, which allowed us
      to simplify the very complicated structure of glycogen. Our results demonstrate
      that there is a molecular size limit that guarantees the structural homogeneity,
      beyond which the structure of the molecule degenerates, as many chains do not
      grow. This strongly suggests that such a size limit is precisely what the
      molecule possesses in the cell.

PMID- 9649372
TI  - Assessment of swelling-activated Cl- channels using the halide-sensitive
      fluorescent indicator 6-methoxy-N-(3-sulfopropyl)quinolinium.
AB  - This study describes a quantitative analysis of the enhancement in anion
      permeability through swelling-activated Cl- channels, using the halide-sensitive
      fluorescent dye 6-methoxy-N-(3-sulfopropyl)quinolinium (SPQ). Cultured bovine
      corneal endothelial monolayers perfused with NO3- Ringer's were exposed to I-
      pulses under isosmotic and, subsequently, hyposmotic conditions. Changes in SPQ
      fluorescence due to I- influx were significantly faster under hyposmotic than
      under isosmotic conditions. Plasma membrane potential (Em) was -58 and -32 mV
      under isosmotic and hyposmotic conditions, respectively. An expression for the
      ratio of I- permeability under hyposmotic condition to that under isosmotic
      condition (termed enhancement ratio or ER) was derived by combining the Stern
      Volmer equation (for modeling SPQ fluorescence quenching by I-) and the Goldman
      flux equation (for modeling the electrodiffusive unidirectional I- influx). The
      fluorescence values and slopes at the inflection points of the SPQ fluorescence
      profile during I- influx, together with Em under isosmotic and hyposmotic
      conditions, were used to calculate ER. Based on this approach, endothelial cells
      were shown to express swelling-activated Cl- channels with ER = 4.9 when the
      hyposmotic shock was 110 +/- 10 mosM. These results illustrate the application of
      the SPQ-based method for quantitative characterization of swelling-activated Cl-
      channels in monolayers.

PMID- 9649373
TI  - Light gradients in spherical photosynthetic vesicles.
AB  - Light-gradient photovoltage measurements were performed on EDTA-treated
      thylakoids and on osmotically swollen thylakoids (blebs), both of spherical
      symmetry but of different sizes. In the case of EDTA vesicles, a negative
      polarity (due to the normal light gradient) was observed in the blue range of the
      absorption spectrum, and a positive polarity, corresponding to an inverse light
      gradient, was observed at lambda = 530 and lambda = 682 nm. The sign of the
      photovoltage polarity measured in large blebs (swollen thylakoids) is the same as
      that obtained for whole chloroplasts, although differences in the amplitudes are
      observed. An approach based on the use of polar coordinates was adapted for a
      theoretical description of these membrane systems of spherical symmetry. The
      light intensity distribution and the photovoltage in such systems were
      calculated. Fits to the photovoltage amplitudes, measured as a function of light
      wavelength, made it possible to derive the values of the dielectric constant of
      the protein, epsilons = 3, and the refractive index of the photosynthetic
      membrane for light propagating perpendicular and parallel to the membrane
      surface, nt = 1.42 and nn = 1.60, respectively. The latter two values determine
      the birefringence of the biological membrane, Deltan = nn - nt = 0.18.

PMID- 9649374
TI  - Structural equilibrium of DNA represented with different force fields.
AB  - We have recently indicated preliminary evidence of different equilibrium average
      structures with the CHARMM and AMBER force fields in explicit solvent molecular
      dynamics simulations on the DNA duplex d(C5T5) . d(A5G5) (Feig, M. and B.M.
      Pettitt, 1997, Experiment vs. Force Fields: DNA conformation from molecular
      dynamics simulations. J. Phys. Chem. B. (101:7361-7363). This paper presents a
      detailed comparison of DNA structure and dynamics for both force fields from
      extended simulation times of 10 ns each. Average structures display an A-DNA base
      geometry with the CHARMM force field and a base geometry that is intermediate
      between A- and B-DNA with the AMBER force field. The backbone assumes B form on
      both strands with the AMBER force field, while the CHARMM force field produces
      heterogeneous structures with the purine strand in A form and the pyrimidine
      strand in dynamical equilibrium between A and B conformations. The results
      compare well with experimental data for the cytosine/guanine part but fail to
      fully reproduce an overall B conformation in the thymine/adenine tract expected
      from crystallographic data, particularly with the CHARMM force field.
      Fluctuations between A and B conformations are observed on the nanosecond time
      scale in both simulations, particularly with the AMBER force field. Different
      dynamical behavior during the first 4 ns indicates that convergence times of
      several nanoseconds are necessary to fully establish a dynamical equilibrium in
      all structural quantities on the time scale of the simulations presented here.

PMID- 9649375
TI  - Diffusion of solvent around biomolecular solutes: a molecular dynamics simulation
      study.
AB  - Effects of the macromolecular solute on the translational mobility of surrounding
      solvent water, and Na+ and Cl- ions are investigated by molecular dynamics (MD)
      simulation. Using MD trajectories of myoglobin and d(C5T5) . d(G5A5) DNA decamer
      of high quality and length, we determine the average diffusion coefficients for
      all solvent species as a function of distance from the closest solute atom. We
      examine solvent mobility in the directions parallel and perpendicular to the
      solute surface and in proximity to three different classes of solute atoms
      (oxygens, nitrogens, and carbons). The nature and the magnitude of the solute
      effects on water diffusion appear to be very similar for protein and DNA decamer.
      The overall diffusion rate at the interface is lower than in the bulk. The rate
      is higher than the average in the direction parallel to the solute surface, and
      lower in the direction normal to the surface, up to 15 A away from the solute.
      The rate is also lower in the solvation shells of the macromolecules, producing
      characteristic depressions in the radial profiles of the diffusion coefficient
      that can be correlated with peaks in the corresponding radial distribution
      functions. The magnitude of these depressions is small compared to the overall
      change in solvent mobility at the interface. Similar features are observed in the
      radial profiles of the diffusion coefficient of sodium and chlorine ions as well.

PMID- 9649376
TI  - Structure, stability, and thermodynamics of lamellar DNA-lipid complexes.
AB  - We develop a statistical thermodynamic model for the phase evolution of DNA
      cationic lipid complexes in aqueous solution, as a function of the ratios of
      charged to neutral lipid and charged lipid to DNA. The complexes consist of
      parallel strands of DNA intercalated in the water layers of lamellar stacks of
      mixed lipid bilayers, as determined by recent synchrotron x-ray measurements.
      Elastic deformations of the DNA and the lipid bilayers are neglected, but DNA
      induced spatial inhomogeneities in the bilayer charge densities are included. The
      relevant nonlinear Poisson-Boltzmann equation is solved numerically, including
      self-consistent treatment of the boundary conditions at the polarized membrane
      surfaces. For a wide range of lipid compositions, the phase evolution is
      characterized by three regions of lipid to DNA charge ratio, rho: 1) for low rho,
      the complexes coexist with excess DNA, and the DNA-DNA spacing in the complex, d,
      is constant; 2) for intermediate rho, including the isoelectric point rho = 1,
      all of the lipid and DNA in solution is incorporated into the complex, whose
      inter-DNA distance d increases linearly with rho; and 3) for high rho, the
      complexes coexist with excess liposomes (whose lipid composition is different
      from that in the complex), and their spacing d is nearly, but not completely,
      independent of rho. These results can be understood in terms of a simple charging
      model that reflects the competition between counterion entropy and inter-DNA (rho
      < 1) and interbilayer (rho > 1) repulsions. Finally, our approach and conclusions
      are compared with theoretical work by others, and with relevant experiments.

PMID- 9649377
TI  - Evidence for a novel bursting mechanism in rodent trigeminal neurons.
AB  - We investigated bursting behavior in rodent trigeminal neurons. The essential
      mechanisms operating in the biological systems were determined based on testable
      predictions of mathematical models. Bursting activity in trigeminal motoneurons
      is consistent with a traditional mechanism employing a region of negative slope
      resistance in the steady-state current-voltage relationship (Smith, T. G. 1975.
      Nature. 253:450-452). However, the bursting dynamics of trigeminal interneurons
      is inconsistent with the traditional mechanisms, and is far more effectively
      explained by a new model of bursting that exploits the unique stability
      properties associated with spike threshold (Baer, S. M., T. Erneux, and J.
      Rinzel. 1989. SIAM J. Appl. Math. 49:55-71).

PMID- 9649378
TI  - Evidence for multiple open and inactivated states of the hKv1.5 delayed
      rectifier.
AB  - The kinetic properties of hKv1.5, a Shaker-related cardiac delayed rectifier,
      expressed in Ltk- cells were studied. hKv1.5 currents elicited by membrane
      depolarizations exhibited a delay followed by biphasic activation. The biphasic
      activation remained after 5-s prepulses to membrane potentials between -80 and 
      30 mV; however, the relative amplitude of the slow component increased as the
      prepulse potential approached the threshold of channel activation, suggesting
      that the second component did not reflect activation from a hesitant state. The
      decay of tail currents at potentials between -80 and -30 mV was adequately
      described with a biexponential. The time course of deactivation slowed as the
      duration of the depolarizing pulse increased. This was due to a relative increase
      in the slowly decaying component, despite similar initial amplitudes reflecting a
      similar open probability after 50- and 500-ms prepulses. To further investigate
      transitions after the initial activated state, we examined the temperature
      dependence of inactivation. The time constants of slow inactivation displayed
      little temperature and voltage dependence, but the degree of the inactivation
      increased substantially with increased temperature. Recovery from inactivation
      proceeded with a biexponential time course, but long prepulses at depolarized
      potentials slowed the apparent rate of recovery from inactivation. These data
      strongly indicate that hKv1.5 has both multiple open states and multiple
      inactivated states.

PMID- 9649379
TI  - Electric field-induced functional reductions in the K+ channels mainly resulted
      from supramembrane potential-mediated electroconformational changes.
AB  - The goal of this study is to distinguish the supramembrane potential difference
      induced electroconformational changes from the huge transmembrane current-induced
      thermal damages in the delayed rectifier K+ channels. A double Vaseline-gap
      voltage clamp was used to deliver shock pulses and to monitor the channel
      currents. Three pairs of 4-ms shock pulses were used to mimic the electric shock
      by a power-line frequency electric field. Each pair consists of two pulses with
      the same magnitude, starting from 350 to 500 mV, but with opposite polarities.
      The shock pulse-generated transmembrane ion flux and the responding electric
      energy, the Joule heating, consumed in the cell membrane, as well as the effects
      on the K+ channel currents, were obtained. Results showed that huge transmembrane
      currents are not necessary to cause damages in the K+ channel proteins. In
      contrast, reductions in the K+ channel currents are directly related to the field
      induced supramembrane potential differences. By a comparison with the shock field
      induced Joule heating effects on cell membranes, the field-induced supramembrane
      potential difference plays a dominant role in damaging the K+ channels, resulting
      in electroconformational changes in the membrane proteins. In contrast, the shock
      field-induced huge transmembrane currents, therefore the thermal effects, play a
      secondary, trivial role.

PMID- 9649380
TI  - Molecular origin of the L-type Ca2+ current of skeletal muscle myotubes
      selectively deficient in dihydropyridine receptor beta1a subunit.
AB  - The origin of Ibetanull, the Ca2+ current of myotubes from mice lacking the
      skeletal dihydropyridine receptor (DHPR) beta1a subunit, was investigated. The
      density of Ibetanull was similar to that of Idys, the Ca2+ current of myotubes
      from dysgenic mice lacking the skeletal DHPR alpha1S subunit (-0.6 +/- 0.1 and 
      0.7 +/- 0.1 pA/pF, respectively). However, Ibetanull activated at significantly
      more positive potentials. The midpoints of the GCa-V curves were 16.3 +/- 1.1 mV
      and 11.7 +/- 1.0 mV for Ibetanull and Idys, respectively. Ibetanull activated
      significantly more slowly than Idys. At +30 mV, the activation time constant for
      Ibetanull was 26 +/- 3 ms, and that for Idys was 7 +/- 1 ms. The unitary current
      of normal L-type and beta1-null Ca2+ channels estimated from the mean variance
      relationship at +20 mV in 10 mM external Ca2+ was 22 +/- 4 fA and 43 +/- 7 fA,
      respectively. Both values were significantly smaller than the single-channel
      current estimated for dysgenic Ca2+ channels, which was 84 +/- 9 fA under the
      same conditions. Ibetanull and Idys have different gating and permeation
      characteristics, suggesting that the bulk of the DHPR alpha1 subunits underlying
      these currents are different. Ibetanull is suggested to originate primarily from
      Ca2+ channels with a DHPR alpha1S subunit. Dysgenic Ca2+ channels may be a minor
      component of this current. The expression of DHPR alpha1S in beta1-null myotubes
      and its absence in dysgenic myotubes was confirmed by immunofluorescence labeling
      of cells.

PMID- 9649381
TI  - A distinct contribution of the delta subunit to acetylcholine receptor channel
      activation revealed by mutations of the M2 segment.
AB  - Acetylcholine receptor (AChR) channels with proline (P) mutations in the putative
      pore-forming domain (at the 12' position of the M2 segment) were examined at the
      single-channel level. For all subunits (alpha, beta, epsilon, and delta), a 12'P
      mutation increased the open channel lifetime >5-fold. To facilitate the
      estimation of binding and gating rate constants, subunits with 12'P mutations
      were co-expressed with alpha subunits having a binding site mutation that slows
      channel opening (alphaD200N). In these AChRs, a 12'P mutation in epsilon or beta
      slowed the closing rate constant approximately 6-fold but had no effect on either
      the channel opening rate constant or the equilibrium dissociation constant for
      ACh (Kd). In contrast, a 12'P mutation in delta slowed the channel closing rate
      constant only approximately 2-fold and significantly increased both the channel
      opening rate constant and the Kd. Pairwise expression of 12'P subunits indicates
      that mutations in epsilon and beta act nearly independently, but one in delta
      reduces the effect of a homologous mutation in epsilon or beta. The results
      suggest that a 12'P mutation in epsilon and beta has mainly local effects,
      whereas one in delta has both local and distributed effects that influence both
      agonist binding and channel gating.

PMID- 9649382
TI  - Anion competition for a volume-regulated current.
AB  - We have examined whether the anionic amino acids, glutamate and aspartate,
      permeate through the same volume-regulated conductance permeant to Cl- ions. Cell
      swelling was initiated in response to establishing a whole-cell configuration in
      the presence of a hyposmotic gradient. Volume-regulated anion currents carried by
      Cl-, glutamate, or aspartate developed with similar time courses and showed
      similar voltage-dependent inactivation. Permeability ratios (Paa/PCl) calculated
      from measured reversal potentials were dependent on the mole fraction ratio (MFR)
      of the permeant anions ([aa]/([aa] + [Cl-])). MFR was varied from 0.00 to 0.97.
      As the fraction of amino acid increased, Paa/PCl decreased. Current amplitude was
      similarly dependent on MFR. These results show that the permeation of anionic
      amino acids and that of Cl- ions are not independent of each other, indicating
      that the ion channel underlying the volume-regulated conductance can be occupied
      by more than one ion at a time. Application of Eyring rate theory indicated that
      the major barrier to Cl- ion permeation is at the intracellular side of the
      membrane, and that the major barrier to amino acid permeation is at the
      extracellular side of the membrane. The interactions between these permeant ions
      may have a physiological modulatory role in volume regulation through a volume
      regulated anion conductance.

PMID- 9649383
TI  - Extrapore residues of the S5-S6 loop of domain 2 of the voltage-gated skeletal
      muscle sodium channel (rSkM1) contribute to the mu-conotoxin GIIIA binding site.
AB  - The tetradomain voltage-gated sodium channels from rat skeletal muscle (rSkM1)
      and from human heart (hH1) possess different sensitivities to the 22-amino-acid
      peptide toxin, mu-conotoxin GIIIA (mu-CTX). rSkM1 is sensitive (IC50 = 51.4 nM)
      whereas hH1 is relatively resistant (IC50 = 5700 nM) to the action of the toxin,
      a difference in sensitivity of >100-fold. The affinity of the mu-CTX for a
      chimera formed from domain 1 (D1), D2, and D3 from rSkM1and D4 from hH1 (SSSH; S
      indicates origin of domain is skeletal muscle and H indicates origin of domain is
      heart) was paradoxically increased approximately fourfold relative to that of
      rSkM1. The source of D3 is unimportant regarding the difference in the relative
      affinity of rSkM1 and hH1 for mu-CTX. Binding of mu-CTX to HSSS was substantially
      decreased (IC50 = 1145 nM). Another chimera with a major portion of D2 deriving
      form hH1 showed no detectable binding of mu-CTX (IC50 > 10 microM). These data
      indicate that D1 and, especially, D2 play crucial roles in forming the mu-CTX
      receptor. Charge-neutralizing mutations in D1 and D2 (Asp384, Asp762, and Glu765)
      had no effect on toxin binding. However, mutations at a neutral and an anionic
      site (residues 728 and 730) in S5-S6/D2 of rSkM1, which are not in the putative
      pore region, were found to decrease significantly the mu-CTX affinity with little
      effect on tetrodotoxin binding (</=1.3-fold increase in affinity). Furthermore,
      substitution at Asp730 with cysteine and exposure to Cd2+ or methanethiosulfonate
      reagents had no significant effect on sodium currents, consistent with this
      residue not contributing to the pore.

PMID- 9649384
TI  - The breakdown of cell membranes by electrical and mechanical stress.
AB  - We attempted to determine whether mechanical tension and electrical stress couple
      to cause membrane breakdown in cells. Using cell-attached patches from HEK293
      cells, we estimated the mechanically produced tension from the applied pressure
      and geometry of the patch. Voltage pulses of increasing amplitude were applied
      until we observed a sudden increase in conductance and capacitance. For pulses of
      50 micros duration, breakdown required >0.5 V and was dependent on the tension.
      For pulses of 50-100 ms duration, breakdown required 0.2-0.4 V and was
      independent of tension. Apparently two physically different processes can lead to
      membrane breakdown. We could explain the response to the short, high-voltage
      pulses if breakdown occurred in the lipid bilayer. The critical electromechanical
      energy per unit area for breakdown by short pulses was approximately 4 dyne/cm,
      in agreement with earlier results on bilayers. Our data suggest that, at least in
      a patch, the bilayer may hold a significant fraction (approximately 40%) of the
      mean tension. To be compatible with the large, nonlytic area changes of patches,
      the bilayer appears to be pulled toward the pipette tip, perhaps by hydrophobic
      forces wetting membrane proteins bound to the glass. Although breakdown voltages
      for long pulses were in agreement with earlier work on algae, the mechanism(s)
      for this breakdown remain unclear.

PMID- 9649385
TI  - Sulfur distribution in bacteriorhodopsin from multiple wavelength anomalous
      diffraction near the sulfur K-edge with synchrotron x-ray radiation.
AB  - Bacteriorhodopsin contains nine sulfur atoms from the nine methionine residues.
      The distribution of these sulfur atoms in the projected density map was
      determined from x-ray diffraction experiments using multiple wavelength anomalous
      diffraction (MAD) at the sulfur K-edge (5.02 A) with synchrotron radiation. The
      experiments were performed with uniaxial samples of oriented purple membranes at
      room temperature and 86% relative humidity. For such samples only the real part
      f' (lambda) of the resonant scattering amplitude of sulfur contributes to the
      observed scattering intensity. The sulfur density was determined from the
      difference in diffraction intensities detected at two wavelengths near the sulfur
      K-edge that were approximately 0.004 A apart. The measured change in f' between
      these two wavelengths corresponds to 6 electron units. This shows that large
      anomalous dispersion effects occur near the sulfur K-edge. The in-plane positions
      of the sulfur atoms of Met32, Met56, and Met209 were determined unambiguously.
      The difference density from Met20, Met60, Met118, and Met145 is concentrated in
      the interior of the seven alpha-helical bundle, overlaps strongly in the
      projected density map, and cannot be resolved at the resolution of these
      experiments (8.2 A). This method of localizing individual sulfur atoms can be
      applied to other two-dimensional protein crystals and is promising in conjunction
      with the site-directed introduction of sulfur atoms by the use of cysteine
      mutants.

PMID- 9649386
TI  - Cholesterol-induced variations in the volume and enthalpy fluctuations of lipid
      bilayers.
AB  - The sound velocity and density of suspensions of large unilamellar liposomes from
      dimyristoylphosphatidylcholine with admixed cholesterol have been measured as a
      function of temperature around the chain melting temperature of the phospholipid.
      The cholesterol-to-phospholipid molar ratio xc has been varied over a wide range
      (0 </= xc </= 0.5). The temperature dependence of the sound velocity number, of
      the apparent specific partial volume of the phospholipid, and of the apparent
      specific adiabatic compressibility have been derived from the measured data.
      These data are particularly discussed with respect to the volume fluctuations
      within the samples. A theoretical relation between the compressibility and the
      excess heat capacity of the bilayer system has been derived. Comparison of the
      compressibilities (and sound velocity numbers) with heat capacity traces display
      the close correlation between these quantities for bilayer systems. This
      correlation appears to be very useful as it allows some of the mechanical
      properties of membrane systems to be calculated from the specific heat capacity
      data and vice versa.

PMID- 9649387
TI  - The influence of polymer molecular weight in lamellar gels based on PEG-lipids.
AB  - We report x-ray scattering, rheological, and freeze-fracture and polarizing
      microscopy studies of a liquid crystalline hydrogel called Lalpha,g. The
      hydrogel, found in DMPC, pentanol, water, and PEG-DMPE mixtures, differs from
      traditional hydrogels, which require high MW polymer, are disordered, and gel
      only at polymer concentrations exceeding an "overlap" concentration. In contrast,
      the Lalpha,g uses very low-molecular-weight polymer-lipids (1212, 2689, and 5817
      g/mole), shows lamellar order, and requires a lower PEG-DMPE concentration to gel
      as water concentration increases. Significantly, the Lalpha,g contains fluid
      membranes, unlike Lbeta' gels, which gel via chain ordering. A recent model of
      gelation in Lalpha phases predicts that polymer-lipids both promote and stabilize
      defects; these defects, resisting shear in all directions, then produce
      elasticity. We compare our observations to this model, with particular attention
      to the dependence of gelation on the PEG MW used. We also use x-ray lineshape
      analysis of scattering from samples spanning the fluid-gel transition to obtain
      the elasticity coefficients kappa and B; this analysis demonstrates that although
      B in particular depends strongly on PEG-DMPE concentration, gelation is
      uncorrelated to changes in membrane elasticity.

PMID- 9649388
TI  - Dynamic excitations in membranes induced by optical tweezers.
AB  - We present the phenomenology of transformations in lipid bilayers that are
      excited by laser tweezers. A variety of dynamic instabilities and shape
      transformations are observed, including the pearling instability, expulsion of
      vesicles, and more exotic ones, such as the formation of passages. Our physical
      picture of the laser-membrane interaction is based on the generation of tension
      in the bilayer and loss of surface area. Although tension is the origin of the
      pearling instability, it does not suffice to explain expulsion of vesicles, where
      we observe opening of giant pores and creeping motion of bilayers. We present a
      quantitative theoretical framework to understand most of the observed
      phenomenology. The main hypothesis is that lipid is pulled into the optical trap
      by the familiar dielectric effect, is disrupted, and finally is repackaged into
      an optically unresolvable suspension of colloidal particles. This suspension, in
      turn, can produce osmotic pressure and depletion forces, driving the observed
      transformations.

PMID- 9649389
TI  - Material property characteristics for lipid bilayers containing lysolipid.
AB  - The apparent area expansion modulus and tensile strength of egg
      phosphatidylcholine (EPC) membranes are measured in the presence of
      monooleoylphosphatidylcholine (MOPC). The apparent area expansion modulus
      decreases from 171 mN m-1 for pure EPC membrane to 82 mN m-1 for a membrane
      containing 30 mol % MOPC. This significant decrease of the apparent area
      expansion modulus is attributed to the change of the membrane area due to the
      tension-dependent exchange of MOPC between the bathing solution and the membrane.
      Similar to the apparent area expansion modulus, the tensile strength of the
      membrane decreases with the increase of the molar concentration of MOPC in the
      membrane. The tensile strength of pure EPC membrane is 9.4 mN m-1 whereas that
      for a membrane containing 30 mol % MOPC is only 1.8 mN m-1, and for a membrane
      containing 50 mol % MOPC it is even smaller, on the order of 0.07 mN m-1. The
      decrease of the tensile strength is coupled with a decrease of the work for
      membrane breakdown, which changes from 4.3 x 10(-2) kT for pure EPC membrane to 2
      x 10(-6) kT for a membrane with 50 mol % MOPC. Overall, these results show that
      the decrease of the apparent area expansion modulus in the presence of
      exchangeable molecules is a fundamental property for all membranes and depends on
      the area occupied by these molecules. The method presented here provides a unique
      tool for measuring the area occupied by an exchangeable molecule in the bilayer
      membrane.

PMID- 9649390
TI  - Water dynamics in glycosphingolipid aggregates studied by LAURDAN fluorescence.
AB  - We have characterized the fluorescence properties of 6-dodecanoyl-2-dimethylamine
      naphthalene (LAURDAN) in pure interfaces formed by sphingomyelin and 10
      chemically related glycosphingolipids (GSLs).1 The GSLs contain neutral and
      anionic carbohydrate residues in their oligosaccharide chain. These systems were
      studied at temperatures below, at, or above the main phase transition temperature
      of the pure lipid aggregates. The extent of solvent dipolar relaxation around the
      excited fluorescence probe in the GSLs series increases with the magnitude of the
      glycosphingolipid polar headgroup below the transition temperature. This
      conclusion is based on LAURDAN's excitation generalized polarization (GPex) and
      fluorescence lifetime values found in the different interfaces. A linear
      dependence between the LAURDAN GPex and the intermolecular spacing among the
      lipid molecules was found for both neutral and anionic lipids in the GSLs series.
      This relationship was also followed by phospholipids. We conclude that LAURDAN in
      these lipid aggregates resides in sites containing different amounts of water.
      The dimension of these sites increases with the size of the GSLs polar headgroup.
      The GP function reports on the concentration and dynamics of water molecules in
      these sites. Upon addition of cholesterol to Gg4Cer, the fluorescence behavior of
      LAURDAN was similar to that of pure cerebrosides and sphingomyelin vesicles. This
      observation was attributed to a change in the interfacial hydration as well as
      changes in the shape and size of the Gg4Cer aggregates in the presence of
      cholesterol. After the addition of cholesterol to gangliosides, the changes in
      the LAURDAN's spectral parameters decrease progressively as the polar headgroup
      of these lipids becomes more complex. This finding suggests that the dehydration
      effect of cholesterol depends strongly on the curvature radius and the extent of
      hydration of these lipid aggregates. In the gel phase of phrenosine, GalCer,
      Gg3Cer, sulfatide, and sphingomyelin, the excitation red band (410 nm) of LAURDAN
      was reduced with respect to that of LAURDAN in the gel phase of pure
      phospholipids. This observation indicates a local environment that interacts
      differently with the ground state of LAURDAN in GSLs when compared with LAURDAN
      in phospholipids.

PMID- 9649391
TI  - Submicron structure in L-alpha-dipalmitoylphosphatidylcholine monolayers and
      bilayers probed with confocal, atomic force, and near-field microscopy.
AB  - Langmuir-Blodgett (LB) monolayers and bilayers of L-alpha
      dipalmitoylphosphatidylcholine (DPPC), fluorescently doped with 1,1'-dioctadecyl
      3,3,3',3'-tetramethylindocarbocyanine perchlorate (diIC18), are studied by
      confocal microscopy, atomic force microscopy (AFM), and near-field scanning
      optical microscopy (NSOM). Beyond the resolution limit of confocal microscopy,
      both AFM and NSOM measurements of mica-supported lipid monolayers reveal small
      domains on the submicron scale. In the NSOM studies, simultaneous high-resolution
      fluorescence and topography measurements of these structures confirm that they
      arise from coexisting liquid condensed (LC) and liquid expanded (LE) lipid
      phases, and not defects in the monolayer. AFM studies of bilayers formed by a
      combination of LB dipping and Langmuir-Schaefer monolayer transfer exhibit
      complex surface topographies that reflect a convolution of the phase structure
      present in each of the individual monolayers. NSOM fluorescence measurements,
      however, are able to resolve the underlying lipid domains from each side of the
      bilayer and show that they are qualitatively similar to those observed in the
      monolayers. The observation of the small lipid domains in these bilayers is
      beyond the spatial resolving power of confocal microscopy and is complicated in
      the topography measurements taken with AFM, illustrating the utility of NSOM for
      these types of studies. The data suggest that the small LC and LE lipid domains
      are formed after lipid transfer to the substrate through a dewetting mechanism.
      The possible extension of these measurements to probing for lipid phase domains
      in natural biomembranes is discussed.

PMID- 9649392
TI  - Nonaxiality in infrared dichroic ratios of polytopic transmembrane proteins.
AB  - In polytopic alpha-helical transmembrane proteins, the distribution of amide
      vibrational transition moments can be nonaxial, if the helix axes are tilted
      relative to the symmetry axis of the helix bundle. The infrared dichroic ratios
      from oriented samples then contain nonaxial terms and, in the most general case,
      require a second-order parameter for the axis of the helix bundle. The extent of
      nonaxiality depends on the summation over the individual amide transition moments
      along the helix. Because this is strongly oscillatory, with a 3.6-residue
      periodicity, complete axial symmetry is not achieved rapidly on progressive
      summation. Expressions for the contributions of residual nonaxiality to the
      dichroic ratios are derived. A similar situation arises for oligomers of
      transmembrane beta-barrel proteins, e.g., the porin trimer. In this case, the
      extent of nonaxiality depends not only on the number of residues in the beta
      barrel, but also on the tilt of the beta-strands relative to the barrel axis and
      the characteristic dimensions of a beta-sheet, which together determine the axial
      periodicity. The nonaxial contributions to the dichroic ratios of beta-barrel
      oligomers are also derived. Estimates are given of the likely size of the
      nonaxial contributions for the different alpha-helical and beta-sheet systems.

PMID- 9649393
TI  - Na-Ca exchange and the trigger for sarcoplasmic reticulum Ca release: studies in
      adult rabbit ventricular myocytes.
AB  - The importance of Na-Ca exchange as a trigger for sarcoplasmic reticulum (SR) Ca
      release remains controversial. Therefore, we measured whole-cell Ca currents
      (ICa), Na-Ca exchange currents (INaCa), cellular contractions, and intracellular
      Ca transients in adult rabbit cardiac myocytes. We found that changing pipette Na
      concentration markedly affected the relationship between cell shortening (or Ca
      transients) and voltage, but did not affect the Ca current-voltage relationship.
      We then inhibited Na-Ca exchange and varied SR content (by changing the number of
      conditioning pulses before each test pulse). Regardless of SR Ca content, the
      relationship between contraction and voltage was bell-shaped in the absence of Na
      Ca exchange. Next, we rapidly and completely blocked ICa by applying nifedipine
      to cells. Cellular shortening was variably reduced in the presence of nifedipine.
      The component of shortening blocked by nifedipine had a bell-shaped relationship
      with voltage, whereas the "nifedipine-insensitive" component of contraction
      increased with voltage. With the SR disabled (ryanodine and thapsigargin
      pretreatment), ICa could initiate late-peaking contractions that were
      approximately 70% of control amplitude. In contrast, nifedipine-insensitive
      contractions could not be elicited in the presence of ryanodine and thapsigargin.
      Finally, we recorded reverse Na-Ca exchange currents that were activated by
      membrane depolarization. The estimated sarcolemmal Ca flux occurring by Na-Ca
      exchange (during voltage clamp steps to +30 mV) was approximately 10-fold less
      than that occurring by ICa. Therefore, Na-Ca exchange alone is unlikely to raise
      cytosolic Ca concentration enough to directly activate the myofilaments. We
      conclude that reverse Na-Ca exchange can trigger SR Ca release. Because of the
      sigmoidal relationship between the open probability of the SR Ca release channel
      and pCa, the effects of ICa and INaCa may not sum in a linear fashion. Rather,
      the two triggers may act synergistically in the modulation of SR release.

PMID- 9649394
TI  - Sequence-dependent dynamics of TATA-Box binding sites.
AB  - We have carried out two nanosecond-length molecular dynamics simulations on a DNA
      oligomer, d(GCGTAAAAAAAACGC)2, which contains a weak binding site for the TATA
      box binding protein. An analysis of the resulting trajectories shows that this
      oligomer behaves differently from a related oligomer [d(GCGTATATAAAACGC)2]
      studied earlier using the same protocol (Flatters, D., M. Young, D. L. Beveridge,
      and R. Lavery. 1997. Conformational properties of the TATA-box binding sequence
      of DNA. J. Biomol. Struct. & Dyn. 14:757-765), and which contains a strong
      binding site for the same protein. The two basepair mutations that relate these
      oligomers lead to significant changes in time-averaged structure and in dynamic
      behavior, which extend over entire length of the oligomer and appear to be
      compatible with the experimentally observed decrease of binding and functional
      activity. These results suggest that molecular dynamics simulations, taking into
      account explicit solvent and counterions, and avoiding the truncation of
      electrostatic interactions, are a powerful tool for investigating the indirect
      aspects of protein-nucleic acid recognition.

PMID- 9649395
TI  - Contribution of proton release to the B2 photocurrent of bacteriorhodopsin.
AB  - The contribution of proton release from the so-called proton release group to the
      microsecond B2 photocurrent from bacteriorhodopsin (bR) oriented in
      polyacrylamide gels was determined. The fraction of the B2 current due to proton
      release was resolved by titration of the proton release group in M. At pH values
      below the pKa of the proton release group in M, the proton release group cannot
      release its proton during the first half of the bacteriorhodopsin photocycle. At
      these pH values, the B2 photocurrent is due primarily to translocation of the
      Schiff base proton to Asp85. The B2 photocurrent was measured in wild-type bR
      gels at pH 4.5-7.5, in 100 mM KCl/50 mM phosphate. The B2 photocurrent area
      (proportional to the amount of charge moved) exhibits a pH dependence with a pKa
      of 6.1. This is suggested to be the pKa of the proton release group in M; the
      value obtained is in good agreement with previous results obtained by examining
      photocycle kinetics and pH-sensitive dye signals. In the mutant Glu204Gln, the B2
      photocurrent of the mutant membranes was pH independent between pH 4 and 7.
      Because the proton release group is incapacitated, and early proton release is
      eliminated in the Glu204Gln mutant, this supports the idea that the pH dependence
      of the B2 photocurrent in the wild type reflects the titration of the proton
      release group. In wild-type bacteriorhodopsin, proton release contributes
      approximately half of the B2 area at pH 7.5. The B2 area in the Glu204Gln mutant
      is similar to that in the wild type at pH 4.5; in both cases, the B2 current is
      likely due only to movement of the Schiff base proton to Asp85.

PMID- 9649396
TI  - Fluorescence and absorption spectroscopy of the weakly fluorescent chlorophyll a
      in cytochrome b6f of Synechocystis PCC6803.
AB  - A spectroscopic characterization of the chlorophyll a (Chl) molecule in the
      monomeric cytochrome b6f complex (Cytb6f) isolated from the cyanobacterium
      Synechocystis PCC6803 is presented. The fluorescence lifetime and quantum yield
      have been determined, and it is shown that Chl in Cytb6f has an excited-state
      lifetime that is 20 times smaller than that of Chl in methanol. This shortening
      of the Chl excited state lifetime is not caused by an increased rate of
      intersystem crossing. Most probably it is due to quenching by a nearby amino
      acid. It is suggested that this quenching is a mechanism for preventing the
      formation of Chl triplets, which can lead to the formation of harmful singlet
      oxygen. Using site-selected fluorescence spectroscopy, detailed information on
      vibrational frequencies in both the ground and Qy excited states has been
      obtained. The vibrational frequencies indicate that the Chl molecule has one
      axial ligand bound to its central magnesium and accepts a hydrogen bond to its
      13(1)-keto carbonyl. The results show that the Chl binds to a well-defined pocket
      of the protein and experiences several close contacts with nearby amino acids.
      From the site-selected fluorescence spectra, it is further concluded that the
      electron-phonon coupling is moderately strong. Simulations of both the site
      selected fluorescence spectra and the temperature dependence of absorption and
      fluorescence spectra are presented. These simulations indicate that the Huang
      Rhys factor characterizing the electron-phonon coupling strength is between 0.6
      and 0.9. The width of the Gaussian inhomogeneous distribution function is 210 +/-
      10 cm-1.

PMID- 9649397
TI  - Evidence for charge-controlled conformational changes in the photocycle of
      bacteriorhodopsin.
AB  - The existence of two different M-state structures in the photocycle of the
      bacteriorhodopsin mutant ASP38ARG was proved. At pH 6.7 (0 to -6 degreesC) a
      spectroscopic M intermediate (M1) that does not differ significantly in its
      tertiary structure from the light-adapted ground state accumulates under
      illumination. At pH > 9 another state (M2), characterized by additional
      pronounced changes in the Fourier transform infrared difference spectrum in the
      region of the amide I and II bands, accumulates. The M2 intermediate trapped at
      pH 9.6 displays the same changes in the x-ray diffraction intensities under
      continuous illumination as previously described for x-ray experiments with the
      mutant ASP96ASN. These observations indicate that in this mutant the altered
      charge distribution at neutral pH controls the tertiary structural changes that
      seem to be necessary for proton translocation.

PMID- 9649398
TI  - New photocycle intermediates in the photoactive yellow protein from
      Ectothiorhodospira halophila: picosecond transient absorption spectroscopy.
AB  - Previous studies have shown that the room temperature photocycle of the
      photoactive yellow protein (PYP) from Ectothiorhodospira halophila involves at
      least two intermediate species: I1, which forms in <10 ns and decays with a 200
      micros lifetime to I2, which itself subsequently returns to the ground state with
      a 140-ms time constant at pH 7 (Genick et al. 1997. Biochemistry. 36:8-14).
      Picosecond transient absorption spectroscopy has been used here to reveal a
      photophysical relaxation process (stimulated emission) and photochemical
      intermediates in the PYP photocycle that have not been reported previously. The
      first new intermediate (I0) exhibits maximum absorption at approximately 510 nm
      and appears in </=3 ps after 452 nm excitation (5 ps pulse width) of PYP. Kinetic
      analysis shows that I0 decays with a 220 +/- 20 ps lifetime, forming another
      intermediate (Idouble dagger0) that has a similar difference wavelength maximum,
      but with lower absorptivity. Idouble dagger0 decays with a 3 +/- 0.15 ns time
      constant to form I1. Stimulated emission from an excited electronic state of PYP
      is observed both within the 4-6-ps cross-correlation times used in this work, and
      with a 16-ps delay for all probe wavelengths throughout the 426-525-nm region
      studied. These transient absorption and emission data provide a more detailed
      understanding of the mechanistic dynamics occurring during the PYP photocycle.

PMID- 9649400
TI  - International symposium on protein condensation, in honor of gregorio weber, may
      21-25, 1997, rio de janeiro, brazil 

PMID- 9649399
TI  - Effective light-induced hydroxylamine reactions occur with C13 = C14
      nonisomerizable bacteriorhodopsin pigments.
AB  - The light-driven proton pump bacteriorhodopsin (bR) undergoes a bleaching
      reaction with hydroxylamine in the dark, which is markedly catalyzed by light.
      The reaction involves cleavage of the (protonated) Schiff base bond, which links
      the retinyl chromophore to the protein. The catalytic light effect is currently
      attributed to the conformational changes associated with the photocycle of all
      trans bR, which is responsible for its proton pump mechanism and is initiated by
      the all-trans --> 13-cis isomerization. This hypothesis is now being tested in a
      series of experiments, at various temperatures, using three artificial bR
      molecules in which the essential C13==C14 bond is locked by a rigid ring
      structure into an all-trans or 13-cis configuration. In all three cases we
      observe an enhancement of the reaction by light despite the fact that, because of
      locking of the C13==C14 bond, these molecules do not exhibit a photocycle, or any
      proton-pump activity. An analysis of the rate parameters excludes the possibility
      that the light-catalyzed reaction takes place during the approximately 20-ps
      excited state lifetimes of the locked pigments. It is concluded that the reaction
      is associated with a relatively long-lived (micros-ms) light-induced
      conformational change that is not reflected by changes in the optical spectrum of
      the retinyl chromophore. It is plausible that analogous changes (coupled to those
      of the photocycle) are also operative in the cases of native bR and visual
      pigments. These conclusions are discussed in view of the light-induced
      conformational changes recently detected in native and artificial bR with an
      atomic force sensor.

PMID- 9649401
TI  - Gregorio Weber, 1916-1997: a fluorescent lifetime.

PMID- 9649402
TI  - A helix propensity scale based on experimental studies of peptides and proteins.
AB  - The average globular protein contains 30% alpha-helix, the most common type of
      secondary structure. Some amino acids occur more frequently in alpha-helices than
      others; this tendency is known as helix propensity. Here we derive a helix
      propensity scale for solvent-exposed residues in the middle positions of alpha
      helices. The scale is based on measurements of helix propensity in 11 systems,
      including both proteins and peptides. Alanine has the highest helix propensity,
      and, excluding proline, glycine has the lowest, approximately 1 kcal/mol less
      favorable than alanine. Based on our analysis, the helix propensities of the
      amino acids are as follows (kcal/mol): Ala = 0, Leu = 0.21, Arg = 0.21, Met =
      0.24, Lys = 0.26, Gln = 0.39, Glu = 0.40, Ile = 0.41, Trp = 0.49, Ser = 0.50, Tyr
      = 0. 53, Phe = 0.54, Val = 0.61, His = 0.61, Asn = 0.65, Thr = 0.66, Cys = 0.68,
      Asp = 0.69, and Gly = 1.

PMID- 9649403
TI  - Protein folding: matching theory and experiment.
AB  - The impact of folding funnels and folding simulations on the way experimentalists
      interpret results is examined. The image of the transition state has changed from
      a unique species that has a strained configuration, with a correspondingly high
      free energy, to a more ordinary folding intermediate, whose balance between
      limited conformational entropy and stabilizing contacts places it at the top of
      the free energy barrier. Evidence for a broad transition barrier comes from
      studies showing that mutations can change the position of the barrier. The main
      controversial issue now is whether populated folding intermediates are productive
      on-pathway intermediates or dead-end traps. Direct experimental evidence is
      needed. Theories suggesting that populated intermediates are trapped in a
      glasslike state are usually based on mechanisms which imply that trapping would
      only be extremely short-lived (e.g., nanoseconds) in water at 25 degrees C. There
      seems to be little experimental evidence for long-lived trapping in monomers, if
      folding aggregates are excluded. On the other hand, there is good evidence for
      kinetic trapping in dimers. alpha-Helix formation is currently the fastest known
      process in protein folding, and incipient helices are present at the start of
      folding. Fast helix formation has the effect of narrowing drastically the choice
      of folding routes. Thus helix formation can direct folding. It changes the
      folding metaphor from pouring liquid down a folding funnel to a train leaving a
      switchyard with only a few choices of exit tracks.

PMID- 9649404
TI  - Thermodynamic volume cycles for electron transfer in the cytochrome c oxidase and
      for the binding of cytochrome c to cytochrome c oxidase.
AB  - Dilatometry is a sensitive technique for measuring volume changes occurring
      during a chemical reaction. We applied it to the reduction-oxidation cycle of
      cytochrome c oxidase, and to the binding of cytochrome c to the oxidase. We
      measured the volume changes that occur during the interconversion of oxidase
      intermediates. The numerical values of these volume changes have allowed the
      construction of a thermodynamic cycle that includes many of the redox
      intermediates. The system volume for each of the intermediates is different. We
      suggest that these differences arise by two mechanisms that are not mutually
      exclusive: intermediates in the catalytic cycle could be hydrated to different
      extents, and/or small voids in the protein could open and close. Based on our
      experience with osmotic stress, we believe that at least a portion of the volume
      changes represent the obligatory movement of solvent into and out of the oxidase
      during the combined electron and proton transfer process. The volume changes
      associated with the binding of cytochrome c to cytochrome c oxidase have been
      studied as a function of the redox state of the two proteins. The volume changes
      determined by dilatometry are large and negative. The data indicate quite clearly
      that there are structural alterations in the two proteins that occur on complex
      formation.

PMID- 9649405
TI  - High-resolution, high-pressure NMR studies of proteins.
AB  - Advanced high-resolution NMR spectroscopy, including two-dimensional NMR
      techniques, combined with high pressure capability, represents a powerful new
      tool in the study of proteins. This contribution is organized in the following
      way. First, the specialized instrumentation needed for high-pressure NMR
      experiments is discussed, with specific emphasis on the design features and
      performance characteristics of a high-sensitivity, high-resolution, variable
      temperature NMR probe operating at 500 MHz and at pressures of up to 500 MPa. An
      overview of several recent studies using 1D and 2D high-resolution, high-pressure
      NMR spectroscopy to investigate the pressure-induced reversible unfolding and
      pressure-assisted cold denaturation of lysozyme, ribonuclease A, and ubiquitin is
      presented. Specifically, the relationship between the residual secondary
      structure of pressure-assisted, cold-denatured states and the structure of early
      folding intermediates is discussed.

PMID- 9649406
TI  - Reversible stalling of transcription elongation complexes by high pressure.
AB  - We have investigated the effect of high hydrostatic pressure on the stability of
      RNA polymerase molecules during transcription. RNA polymerase molecules
      participating in stalled or active ternary transcribing complexes do not
      dissociate from the template DNA and nascent RNA at pressures up to 180 MPa. A
      lower limit for the free energy of stabilization of an elongating ternary complex
      relative to the quaternary structure of the free RNAP molecules is estimated to
      be 20 kcal/mol. The rate of elongation decreases at high pressure; transcription
      completely halts at sufficiently high pressure. The overall rate of elongation
      has an apparent activation volume (DeltaVdouble dagger) of 55-65 ml . mol-1 (at
      35 degrees C). The pressure-stalled transcripts are stable and resume elongation
      at the prepressure rate upon decompression. The efficiency of termination
      decreases at the rho-independent terminator tR2 after the transcription reaction
      has been exposed to high pressure. This suggests that high pressure modifies the
      ternary complex such that termination is affected in a manner different from that
      of elongation. The solvent and temperature dependence of the pressure-induced
      inhibition show evidence for major conformational changes in the core polymerase
      enzyme during RNA synthesis. It is proposed that the inhibition of the elongation
      phase of the transcription reaction at elevated pressures is related to a
      reduction of the partial specific volume of the RNA polymerase molecule; under
      high pressure, the RNA polymerase molecule does not have the necessary structural
      flexibility required for the protein to translocate.

PMID- 9649407
TI  - Determination of the volume changes for pressure-induced transitions of
      apomyoglobin between the native, molten globule, and unfolded states.
AB  - The volume change for the transition from the native state of horse heart
      apomyoglobin to a pressure-induced intermediate with fluorescence properties
      similar to those of the well-established molten globule or I form was measured to
      be -70 ml/mol. Complete unfolding of the protein by pressure at pH 4.2 revealed
      an upper limit for the unfolding of the intermediate of -61 ml/mol. At 0.3 M
      guanidine hydrochloride, the entire transition from native to molten globule to
      unfolded state was observed in the available pressure range below 2.5 kbar. The
      volume change for the N-->I transition is relatively large and does not correlate
      well with the changes in relative hydration for these transitions derived from
      measurements of the changes in heat capacity, consistent with the previously
      observed lack of correlation between the m-value for denaturant-induced
      transitions and the measured volume change of unfolding for cooperativity mutants
      of staphylococcal nuclease (Frye et al. 1996. Biochemistry. 35:10234-10239). Our
      results support the hypothesis that the volume change associated with the
      hydration of protein surface upon unfolding may involve both positive and
      negative underlying contributions that effectively cancel, and that the measured
      volume changes for protein structural transitions arise from another source,
      perhaps the elimination of void volume due to packing defects in the structured
      chains.

PMID- 9649408
TI  - Pressure-induced subunit dissociation and unfolding of dimeric beta
      lactoglobulin.
AB  - Effects of hydrostatic pressure on dimeric beta-lactoglobulin A (beta-Lg) were
      investigated. Application of pressures of up to 3.5 kbar induced a significant
      red shift ( approximately 11 nm) and a 60% increase in intrinsic fluorescence
      emission of beta-Lg. These changes were very similar to those induced by
      guanidine hydrochloride, which caused subunit dissociation and unfolding of beta
      Lg. A large hysteresis in the recovery of fluorescence parameters was observed
      upon decompression of beta-Lg. Pressure-induced dissociation and unfolding were
      not fully reversible, because of the formation of a nonnative intersubunit
      disulfide bond that hampered correct refolding of the dimer. Comparison between
      pressure dissociation/unfolding at 3 degrees C and 23 degrees C revealed a marked
      destabilization of beta-Lg at low temperature. The stability of beta-Lg toward
      pressure was significantly enhanced by 1 M NaCl, but not by glycerol (up to 20%
      v/v). These observations suggest that salt stabilization was not related to a
      general cosolvent effect, but may reflect charge screening. Interestingly,
      pressure-induced dissociation/unfolding was completely independent of beta-Lg
      concentration, in apparent violation of the law of mass action. Possible causes
      for this anomalous behavior are discussed.

PMID- 9649409
TI  - Differential halothane binding and effects on serum albumin and myoglobin.
AB  - To understand further the weak molecular interactions between inhaled anesthetics
      and proteins, we studied the character and dynamic consequences of halothane
      binding to bovine serum albumin (BSA) and myoglobin using photoaffinity labeling
      and hydrogen-tritium exchange (HX). We find that halothane binds saturably and
      with submillimolar affinity to BSA, but either nonspecifically or with
      considerably lower affinity to myoglobin. Titration of halothane binding with
      guanidine hydrochloride suggested more protection of binding sites from solvent
      in BSA as compared with myoglobin. Protection factors for slowly exchanging
      albumin hydrogens are increased in a concentration-dependent manner by up to 27
      fold with 10 mM halothane, whereas more rapidly exchanging groups of albumin
      hydrogens have either unaltered or decreased protection factors. Protection
      factors for slowly exchanging hydrogens in myoglobin are decreased by halothane,
      suggesting destabilization through binding to an intermediate or completely
      unfolded conformer. These results demonstrate the conformation dependence of
      halothane binding and clear dynamic consequences that correlate with the
      character of binding in these model proteins. Preferential binding and
      stabilization of different conformational states may underlie anesthetic-induced
      protein dysfunction, as well as provide an explanation for heterogeneity of
      action.

PMID- 9649410
TI  - Chemical denaturation: potential impact of undetected intermediates in the free
      energy of unfolding and m-values obtained from a two-state assumption.
AB  - The chemical unfolding transition of a protein was simulated, including the
      presence of an intermediate (I) in equilibrium with the native (N) and unfolded
      (U) states. The calculations included free energies of unfolding, DeltaGuw, in
      the range of 1.4 kcal/mol to 10 kcal/mol and three different global m-values. The
      simulations included a broad range of equilibrium constants for the N left arrow
      over right arrow I process. The dependence of the N <--> I equilibrium on the
      concentration of denaturant was also included in the simulations. Apparent
      DeltaGuw and m-values were obtained from the simulated unfolding transitions by
      fitting the data to a two-state unfolding process. The potential errors were
      calculated for two typical experimental situations: 1) the unfolding is monitored
      by a physical property that does not distinguish between native and intermediate
      states (case I), and 2) the physical property does not distinguish between
      intermediate and unfolded states (case II). The results obtained indicated that
      in the presence of an intermediate, and in both experimental situations, the free
      energy of unfolding and the m-values could be largely underestimated. The errors
      in DeltaGuw and m-values do not depend on the m-values that characterize the
      global N <--> U transition. They are dependent on the equilibrium constant for
      the N <--> I transition and its characteristic m1-value. The extent of the
      underestimation increases for higher energies of unfolding. Including no random
      error in the simulations, it was estimated that the underestimation in DeltaGuw
      could range between 25% and 35% for unfolding transitions of 3-10 kcal/mol (case
      I). In case II, the underestimation in DeltaGuw could be even larger than in case
      I. In the same energy range, a 50% error in the m-value could also take place.
      The fact that most of the mutant proteins are characterized by both a lower m
      value and a lower stability than the wild-type protein suggests that in some
      cases the results could have been underestimated due to the application of the
      two-state assumption.

PMID- 9649411
TI  - Partition and permeation of dextran in polyacrylamide gel.
AB  - Partition of sized FITC-dextrans in polyacrylamide gel showed a relationship
      between Kav and solute radius as predicted by the theory of Ogston, which is
      based solely on geometry of the spaces. Permeability data for the same dextrans
      were fit to several theories, including those based on geometry and those based
      on hydrodynamic interactions, and the gel structure predicted by the partition
      and permeability data were compared. The Brinkman effective-medium model (based
      on hydrodynamic interactions and requiring a measure of the hydraulic
      conductivity of the matrix) gave the best fit of permeability data with the
      values for fiber radius (rf) and void volume of the gel (epsilon) that were
      obtained from the partition data. The models based on geometry and the
      hydrodynamic screening model of Cukier, using the rf and epsilon from partition
      data, all predicted higher rates of permeation than observed experimentally,
      while the effective-medium model with added term for steric interaction predicted
      lower permeation than that observed. The size of cylindrical pores appropriate
      for the partition data predicted higher rates of permeation than observed. These
      relative results were unaffected by the method of estimating void volume of the
      gel. In sum, it appears that one can use data on partition of solute, combined
      with measurement of hydraulic conductivity, to predict solute permeation in
      polyacrylamide gel.

PMID- 9649412
TI  - Model for the fluorescence induction curve of photoinhibited thylakoids.
AB  - The fluorescence induction curve of photoinhibited thylakoids measured in the
      presence of 3-(3,4-dichlorophenyl)-1,1-dimethyl urea was modeled using an
      extension of the model of Lavergne and Trissl (Biophys. J. 68:2474-2492), which
      takes into account the reversible exciton trapping by photosystem II (PSII)
      reaction centers and exciton exchange between PSII units. The model of Trissl and
      Lavergne was modified by assuming that PSII consists of photosynthetically active
      and photoinhibited (inactive in oxygen evolution) units and that the inactive
      PSII units can efficiently dissipate energy even if they still retain the
      capacity for the charge separation reaction. Comparison of theoretical and
      experimental fluorescence induction curves of thylakoids, which had been
      subjected to strong light in the presence of the uncoupler nigericin, suggests
      connectivity between the photoinhibited and active PSII units. The model predicts
      that photoinhibition lowers the yield of radical pair formation in the remaining
      active PSII centers. However, the kinetics of PSII inactivation in nigericin
      treated thylakoids upon exposure to photoinhibitory light ranging from 185 to
      2650 micromol photons m-2 s-1 was strictly exponential. This may suggest that
      photoinhibition occurs independently of the primary electron transfer reactions
      of PSII or that increased production of harmful substances by photoinhibited PSII
      units compensates for the protection afforded by the quenching of excitation
      energy in photoinhibited centers.

PMID- 9649413
TI  - Scanning force microscopy of DNA molecules elongated by convective fluid flow in
      an evaporating droplet.
AB  - Scanning force microscopy (SFM) was used to image intact, nearly fully elongated
      lambda bacteriophage DNA molecules, fixed onto freshly cleaved mica surfaces.
      Molecular elongation and fixation were accomplished using a newly characterized
      fixation technique, termed "fluid fixation." Here convective fluid flows
      generated within an evaporating droplet of DNA solution efficiently elongate DNA
      molecules for fixation onto suitably charged surfaces. SFM images of a very large
      bacteriophage genome, G, showed the presence of double-stranded bubbles. We
      speculate that these structures may contain putative replication forks. Overall,
      the experiments presented here demonstrate the viability of using fluid fixation
      for the preparation of DNA molecules for SFM imaging. The combination of largely
      automatable optically based techniques with the high-resolution SFM imaging
      presented here will likely produce a high-throughput system for detailed physical
      mapping of genomic DNA or clones.

PMID- 9649414
TI  - Real-time observation of conformational fluctuations in Zn-substituted myoglobin
      by time-resolved transient hole-burning spectroscopy.
AB  - Equilibrium fluctuations of the protein conformation have been studied in
      myoglobin by a novel method of time-resolved transient hole-burning spectroscopy
      over a temperature range of 180-300 K and a time range of 10 ns to 10 ms. The
      temporal shift of the hole spectrum has been observed in a wide temperature
      region of 200-300 K. It has been found that the time behavior of the peak
      position of the hole is highly nonexponential and can be expressed by a stretched
      exponential function with a beta value of 0.22. As compared with the results for
      a dye solution sample, the time scale of the fluctuation of the protein
      conformation is much more weakly dependent on temperature. The time scale of the
      observed conformational dynamics shows a temperature dependence similar to that
      associated with the ligand escape process of myoglobin.

PMID- 9649415
TI  - Time-resolved analysis of macromolecular structures during reactions by stopped
      flow electrooptics.
AB  - A stopped-flow field-jump instrument and its use for the analysis of
      macromolecular structure changes during reactions is described. The operation of
      the new instrument is simple and reliable, owing to a new type of cell
      construction with electrodes directly integrated in a quartz cuvette: major
      advantages are the relatively low demand on sample quantities and a high time
      resolution. The stopped flow is characterized by a dead time of approximately 0.5
      ms. Electric field pulses with field strengths up to 20 kV/cm and rise times in
      the nanosecond range are applied at adjustable times after stop of the flow. The
      time resolution of the optical detection is up to the nanosecond time range. The
      instrument may be used for the combination of stopped flow with temperature-jump
      and field-jump experiments. A particularly useful new application is the analysis
      of macromolecular reactions by electrooptical measurements, because
      electrooptical data provide information about structures. This is demonstrated
      for the intercalation of ethidium into double-helical DNA. The transients,
      measured at 313 nm, where the signal is exclusively due to ethidium bound to the
      DNA, demonstrate a relatively high negative dichroism at 0.5 ms after mixing. The
      absolute value of this negative dichroism increases in the millisecond time range
      and approaches the equilibrium value within about a second. The dichroism decay
      time constants demonstrate a clear increase of the effective DNA length due to
      ethidium binding, already 0.5 ms after mixing; a further increase to the
      equilibrium value is found in the millisecond time range. The analysis of these
      data demonstrate the existence of up to three relaxation processes, depending on
      the conditions of the experiments. The dichroism amplitudes, together with the
      decay time constants, indicate that all the reaction states found in the present
      investigation are complexes with insertion of ethidium residues between
      basepairs. Moreover, the data clearly show the degree of intercalation in the
      intermediate states, which is very useful information for the quantitative
      assignment of the mechanism.

PMID- 9649416
TI  - ATP-Induced phosphorylation of the sarcoplasmic reticulum Ca2+ ATPase: molecular
      interpretation of infrared difference spectra.
AB  - Time-resolved infrared difference spectra of the ATP-induced phosphorylation of
      the sarcoplasmic reticulum Ca2+-ATPase have been recorded in H2O and 2H2O at pH
      7.0 and 1 degrees C. The reaction was induced by ATP release from P3-1-(2
      nitro)phenylethyladenosine 5'-triphosphate (caged ATP) and from [gamma-18O3]caged
      ATP. A band at 1546 cm-1, not observed with the deuterated enzyme, can be
      assigned to the amide II mode of the protein backbone and indicates that a
      conformational change associated with ATPase phosphorylation takes place after
      ATP binding. This is also indicated between 1700 and 1610 cm-1, where bandshifts
      of up to 10 cm-1 observed upon protein deuteration suggest that amide I modes of
      the protein backbone dominate the difference spectrum. From the band positions it
      is deduced that alpha-helical, beta-sheet, and probably beta-turn structures are
      affected in the phosphorylation reaction. Model spectra of acetyl phosphate,
      acetate, ATP, and ADP suggest the tentative assignment of some of the bands of
      the phosphorylation spectrum to the molecular groups of ATP and Asp351, which
      participate directly in the phosphate transfer reaction: a positive band at 1719
      cm-1 to the C==O group of aspartyl phosphate, a negative band at 1239 cm-1 to the
      nuas(PO2-) modes of the bound ATP molecule, and a positive band at 1131 cm-1 to
      the nuas(PO32-) mode of the phosphoenzyme phosphate group, the latter assignment
      being supported by the band's sensitivity toward isotopic substitution in the
      gamma-phosphate of ATP. Band positions and shapes of these bands indicate that
      the alpha- and/or beta-phosphate(s) of the bound ATP molecule become partly
      dehydrated when ATP binds to the ATPase, that the phosphoenzyme phosphate group
      is unprotonated at pH 7.0, and that the C==O group of aspartyl phosphate does not
      interact with bulk water. The Ca2+ binding sites seem to be largely undisturbed
      by the phosphorylation reaction, and a functional role of the side chains of Asn,
      Gln, and Arg residues was not detected.

PMID- 9649417
TI  - Energy of adhesion of human T cells to adsorption layers of monoclonal antibodies
      measured by a film trapping technique.
AB  - A novel method for studying the interaction of biological cells with interfaces
      (e.g., adsorption monolayers of antibodies) is developed. The method is called
      the film trapping technique because the cell is trapped within an aqueous film of
      equilibrium thickness smaller than the cell diameter. A liquid film of uneven
      thickness is formed around the trapped cell. When observed in reflected
      monochromatic light, this film exhibits an interference pattern of concentric
      bright and dark fringes. From the radii of the fringes one can restore the shape
      of interfaces and the cell. Furthermore, one can calculate the adhesive energy
      between the cell membrane and the aqueous film surface (which is covered by a
      layer of adsorbed proteins and/or specific ligands), as well as the disjoining
      pressure, representing the force of interaction per unit area of the latter film.
      The method is applied to two human T cell lines: Jurkat and its T cell receptor
      negative (TCR-) derivative. The interaction of these cells with monolayers of
      three different monoclonal antibodies adsorbed at a water-air interface is
      studied. The results show that the adhesive energy is considerable (above 0.5
      mJ/m2) when the adsorption monolayer contains antibodies acting as specific
      ligands for the receptors expressed on the cell surface. In contrast, the
      adhesive energy is close to zero in the absence of such a specific ligand
      receptor interaction. In principle, the method can be applied to the study of the
      interaction of a variety of biological cells (B cells, natural killer cells, red
      blood cells, etc.) with adsorption monolayers of various biologically active
      molecules. In particular, film trapping provides a tool for the gentle
      micromanipulation of cells and for monitoring of processes (say the activation of
      a T lymphocyte) occurring at the single-cell level.

PMID- 9649418
TI  - Analysis of fluorophore diffusion by continuous distributions of diffusion
      coefficients: application to photobleaching measurements of multicomponent and
      anomalous diffusion.
AB  - Fluorescence recovery after photobleaching (FRAP) is widely used to measure
      fluorophore diffusion in artificial solutions and cellular compartments. Two new
      strategies to analyze FRAP data were investigated theoretically and applied to
      complex systems with anomalous diffusion or multiple diffusing species: 1)
      continuous distributions of diffusion coefficients, alpha(D), and 2) time
      dependent diffusion coefficients, D(t). A regression procedure utilizing the
      maximum entropy method was developed to resolve alpha(D) from fluorescence
      recovery curves, F(t). The recovery of multi-component alpha(D) from simulated
      F(t) with random noise was demonstrated and limitations of the method were
      defined. Single narrow Gaussian alpha(D) were recovered for FRAP measurements of
      thin films of fluorescein and size-fractionated FITC-dextrans and Ficolls, and
      multi-component alpha(D) were recovered for defined fluorophore mixtures. Single
      Gaussian alpha(D) were also recovered for solute diffusion in viscous media
      containing high dextran concentrations. To identify anomalous diffusion from FRAP
      data, a theory was developed to compute F(t) and alpha(D) for anomalous diffusion
      models defined by arbitrary nonlinear mean-squared displacement <x2> versus time
      relations. Several characteristic alpha(D) profiles for anomalous diffusion were
      found, including broad alpha(D) for subdiffusion, and alpha(D) with negative
      amplitudes for superdiffusion. A method to deduce apparent D(t) from F(t) was
      also developed and shown to provide useful complementary information to alpha(D).
      alpha(D) and D(t) were determined from photobleaching measurements of systems
      with apparent anomalous subdiffusion (nonuniform solution layer) and
      superdiffusion (moving fluid layer). The results establish a practical strategy
      to characterize complex diffusive phenomena from photobleaching recovery
      measurements.

PMID- 9649419
TI  - A possible molecular mechanism governing human erythrocyte shape.

PMID- 9649420
TI  - Does the transmembrane potential (Deltapsi) or the intracellular pH (pHi) control
      the shape of human erythrocytes?

PMID- 9649421
TI  - Transducing Hedgehog: the story so far.
AB  - The secreted proteins of the Hedgehog family have been implicated in many
      different processes in vertebrate development including cartilage
      differentiation, myotome and sclerotome specification, hair follicle development,
      limb morphogenesis and the specification of different neuronal cell types. In
      addition, the aberrant activation of the Hedgehog pathway has been identified as
      the likely cause of a number of tumours in humans including basal cell carcinomas
      (BCCs) and primitive neurectodermal tumours (PNETs). Elucidating the mechanisms
      by which Hedgehog signals are transduced will thus have widespread implications
      for our understanding of both normal development and disease.

PMID- 9649422
TI  - Potent enzyme inhibitors derived from dromedary heavy-chain antibodies.
AB  - Evidence is provided that dromedary heavy-chain antibodies, in vivo-matured in
      the absence of light chains, are a unique source of inhibitory antibodies. After
      immunization of a dromedary with bovine erythrocyte carbonic anhydrase and
      porcine pancreatic alpha-amylase, it was demonstrated that a considerable amount
      of heavy-chain antibodies, acting as true competitive inhibitors, circulate in
      the bloodstream. In contrast, the conventional antibodies apparently do not
      interact with the enzyme's active site. Next we illustrated that peripheral blood
      lymphocytes are suitable for one-step cloning of the variable domain fragments in
      a phage-display vector. By bio-panning, several antigen-specific single-domain
      fragments are readily isolated for both enzymes. In addition we show that among
      those isolated fragments active site binders are well represented. When produced
      as recombinant protein in Escherichia coli, these active site binders appear to
      be potent enzyme inhibitors when tested in chromogenic assays. The low complexity
      of the antigen-binding site of these single-domain antibodies composed of only
      three loops could be valuable for designing smaller synthetic inhibitors.

PMID- 9649423
TI  - Towards a solution for hepatitis C virus hypervariability: mimotopes of the
      hypervariable region 1 can induce antibodies cross-reacting with a large number
      of viral variants.
AB  - The hypervariable region 1 (HVR1) of the putative envelope protein E2 of
      hepatitis C virus (HCV) is the most variable antigenic fragment in the whole
      viral genome and is mainly responsible for the large inter-and intra-individual
      heterogeneity of the infecting virus. It contains a principal neutralization
      epitope and has been proposed as the major player in the mechanism of escape from
      host immune response. Since anti-HVR1 antibodies are the only species shown to
      possess protective activity up to date, developing an effective prevention
      therapy is a very difficult task. We have approached the problem of HVR1
      variability by deriving a consensus profile from >200 HVR1 sequences from
      different viral isolates and used it as a template to generate a vast repertoire
      of synthetic HVR1 surrogates displayed on M13 bacteriophage. This library was
      affinity selected using many different sera from infected patients. Phages were
      identified which react very frequently with patients' sera and bind serum
      antibodies that cross-react with a large panel of HVR1 peptides derived from
      natural HCV variants. When injected into experimental animals, the 'mimotopes'
      with the highest cross-reactivity induced antibodies which recognized the same
      panel of natural HVR1 variants. In these mimotopes we identified a sequence
      pattern responsible for the observed cross-reactivity. These data may hold the
      key for future development of a prophylactic vaccine against HCV.

PMID- 9649424
TI  - Direct link between cytokine activity and a catalytic site for macrophage
      migration inhibitory factor.
AB  - Macrophage migration inhibitory factor (MIF) is a secreted protein that activates
      macrophages, neutrophils and T cells, and is implicated in sepsis, adult
      respiratory distress syndrome and rheumatoid arthritis. The mechanism of MIF
      function, however, is unknown. The three-dimensional structure of MIF is unlike
      that of any other cytokine, but bears striking resemblance to three microbial
      enzymes, two of which possess an N-terminal proline that serves as a catalytic
      base. Human MIF also possesses an N-terminal proline (Pro-1) that is invariant
      among all known homologues. Multiple sequence alignment of these MIF homologues
      reveals additional invariant residues that span the entire polypeptide but are in
      close proximity to the N-terminal proline in the folded protein. We find that p
      hydroxyphenylpyruvate, a catalytic substrate of MIF, binds to the N-terminal
      region and interacts with Pro-1. Mutation of Pro-1 to a glycine substantially
      reduces the catalytic and cytokine activity of MIF. We suggest that the
      underlying biological activity of MIF may be based on an enzymatic reaction. The
      identification of the active site should facilitate the development of structure
      based inhibitors.

PMID- 9649425
TI  - Elongation and clustering of glycosomes in Trypanosoma brucei overexpressing the
      glycosomal Pex11p.
AB  - Kinetoplastid protozoa confine large parts of glycolysis within glycosomes, which
      are microbodies related to peroxisomes. We cloned the gene encoding the second
      most abundant integral membrane protein of Trypanosoma brucei glycosomes. The 24
      kDa protein is very basic and hydrophobic, with two predicted transmembrane
      domains. It is targeted to peroxisomes when expressed in mammalian cells and
      yeast. The protein is a functional homologue of Pex11p from Saccharomyces
      cerevisiae: pex11Delta mutants, which are defective in peroxisome proliferation,
      can be complemented by the trypanosome gene. Sequence conservation is significant
      in the N- and C-terminal domains of all putative Pex11p homologues known, from
      trypanosomes, yeasts and mammals. Several lines of evidence indicate that these
      domains are oriented towards the cytosol. TbPex11p can form homodimers, like its
      yeast counterpart. The TbPEX11 gene is essential in trypanosomes. Inducible
      overexpression of the protein in T.brucei bloodstream forms causes growth arrest,
      the globular glycosomes being transformed to clusters of long tubules filling
      significant proportions of the cytoplasm. Reduced expression results in
      trypanosomes with fewer, but larger, organelles.

PMID- 9649426
TI  - Yeast PKA represses Msn2p/Msn4p-dependent gene expression to regulate growth,
      stress response and glycogen accumulation.
AB  - Yeast cAMP-dependent protein kinase (PKA) activity is essential for growth and
      antagonizes induction of the general stress response as well as accumulation of
      glycogen stores. Previous studies have suggested that the PKA effects on the two
      latter processes result in part from transcription repression. Here we show that
      transcription derepression that accompanies PKA depletion is dependent upon the
      presence of two redundant Zn2+-finger transcription factors, Msn2p and Msn4p. The
      Msn2p and Msn4p proteins were shown previously to act as positive transcriptional
      factors in the stress response pathway, and our results suggest that Msn2p and
      Msn4p also mediate PKA-dependent effects on stress response as well as glycogen
      accumulation genes. Interestingly, PKA activity is dispensable in a strain
      lacking Msn2p and Msn4p activity. Thus, Msn2p and Msn4p may antagonize
      PKAdependent growth by stimulating expression of genes that inhibit growth. In
      agreement with this model, Msn2p/Msn4p function is required for expression of a
      gene, YAK1, previously shown to antagonize PKA-dependent growth. These results
      suggest that Msn2p/Msn4p-dependent gene expression may account for all, or at
      least most, of the pleiotropic effects of yeast PKA, including growth regulation,
      response to stress and carbohydrate store accumulation.

PMID- 9649427
TI  - Fizzy is required for activation of the APC/cyclosome in Xenopus egg extracts.
AB  - The Xenopus homologue of Drosophila Fizzy and budding yeast CDC20 has been
      characterized. The encoded protein (X-FZY) is a component of a high molecular
      weight complex distinct from the APC/cyclosome. Antibodies directed against FZY
      were produced and shown to prevent calmodulin-dependent protein kinase II
      (CaMKII) from inducing the metaphase to anaphase transition of spindles assembled
      in vitro in Xenopus egg extracts, and this was associated with suppression of the
      degradation of mitotic cyclins. The same antibodies suppressed M phase-promoting
      factor (MPF)-dependent activation of the APC/cyclosome in interphase egg
      extracts, although they did not appear to alter the pattern or extent of MPF
      dependent phosphorylation of APC/cyclosome subunits. As these phosphorylations
      are thought to be essential for APC/cyclosome activation in eggs and early
      embryos, we conclude that at least two events are required for MPF to activate
      the APC/cyclosome, allowing both chromatid segregation and full degradation of
      mitotic cyclins. The first one, which does not require FZY function, is the
      phosphorylation of APC/cyclosome subunits. The second one, that requires FZY
      function (even in the absence of MAD2 protein and when the spindle assembly
      checkpoint is not activated) is not yet understood at its molecular level.

PMID- 9649428
TI  - Bax-mediated cell death by the Gax homeoprotein requires mitogen activation but
      is independent of cell cycle activity.
AB  - Tissues with the highest rates of proliferation typically exhibit the highest
      frequencies of apoptosis, but the mechanisms that coordinate these processes are
      largely unknown. The homeodomain protein Gax is down-regulated when quiescent
      cells are stimulated to proliferate, and constitutive Gax expression inhibits
      cell proliferation in a p21(WAF/CIP)-dependent manner. To understand how mitogen
      induced proliferation influences the apoptotic process, we investigated the
      effects of deregulated Gax expression on cell viability. Forced Gax expression
      induced apoptosis in mitogen-activated cultures, but quiescent cultures were
      resistant to cell death. Though mitogen activation was required for apoptosis,
      neither the cdk inhibitor p21(WAF/CIP) nor the tumor suppressor p53 was required
      for Gax-induced cell death. Arrest in G1 or S phases of the cell cycle with
      chemical inhibitors also did not affect apoptosis, further suggesting that Gax
      mediated cell death is independent of cell cycle activity. Forced Gax expression
      led to Bcl-2 down-regulation and Bax up-regulation in mitogen-activated, but not
      quiescent cultures. Mouse embryonic fibroblasts homozygous null for the Bax gene
      were refractive to Gax-induced apoptosis, demonstrating the functional
      significance of this regulation. These data suggest that the homeostatic balance
      between cell growth and death can be controlled by mitogen-dependent pathways
      that circumvent the cell cycle to alter Bcl-2 family protein expression.

PMID- 9649429
TI  - p53 facilitates pRb cleavage in IL-3-deprived cells: novel pro-apoptotic activity
      of p53.
AB  - In the interleukin-3 (IL-3)-dependent lymphoid cell line DA-1, functional p53 is
      required for efficient apoptosis in response to IL-3 withdrawal. Activation of
      p53 in these cells, by either DNA damage or p53 overexpression, results in a
      vital growth arrest in the presence of IL-3 and in accelerated apoptosis in its
      absence. Thus, IL-3 can control the choice between p53-dependent cell-cycle
      arrest and apoptosis. Here we report that the cross-talk between p53 and IL-3
      involves joint control of pRb cleavage and degradation. Depletion of IL-3 results
      in caspase-mediated pRb cleavage, occurring preferentially within cells which
      express functional p53. Moreover, pRb can be cleaved efficiently by extracts
      prepared from DA-1 cells but not from their derivatives which lack p53 function.
      Inactivation of pRb through expression of the human papillomavirus (HPV) E7
      oncogene overrides the effect of IL-3 in a p53-dependent manner. Our data suggest
      a novel role for p53 in the regulation of cell death and a novel mechanism for
      the cooperation between p53 and survival factor deprivation. Thus, p53 makes
      cells permissive to pRb cleavage, probably by controlling the potential activity
      of a pRb-cleaving caspase, whereas IL-3 withdrawal provides signals that turn on
      this potential activity and lead to the actual cleavage and subsequent
      degradation of pRb. Elimination of a presumptive anti-apoptotic effect of pRb may
      then facilitate conversion of p53-mediated growth arrest into apoptosis.

PMID- 9649430
TI  - Aut2p and Aut7p, two novel microtubule-associated proteins are essential for
      delivery of autophagic vesicles to the vacuole.
AB  - AUT2 and AUT7, two novel genes essential for autophagocytosis in the yeast
      Saccharomyces cerevisiae were isolated. AUT7 was identified as a low copy
      suppressor of autophagic defects in aut2-1 cells. Aut7p is a homologue of the rat
      microtubule-associated protein (MAP) light chain 3 (LC3). Aut2p and Aut7p
      interact physically. Aut7p is attached to microtubules via Aut2p, which interacts
      with tubulins Tub1p and Tub2p. aut2- and aut7-deleted cells are unable to deliver
      autophagic vesicles and the precursor of aminopeptidase I to the vacuole. Double
      membrane-layered autophagosome-like vesicles accumulate in the cytoplasm of these
      cells. Our findings suggest that microtubules and an attached protein complex of
      Aut2p and Aut7p are involved in the delivery of autophagic vesicles to the
      vacuole.

PMID- 9649431
TI  - The ubiquitin-conjugating enzyme Pex4p of Hansenula polymorpha is required for
      efficient functioning of the PTS1 import machinery.
AB  - We have cloned the Hansenula polymorpha PEX4 gene by functional complementation
      of a peroxisome-deficient mutant. The PEX4 translation product, Pex4p, is a
      member of the ubiquitin-conjugating enzyme family. In H.polymorpha, Pex4p is a
      constitutive, low abundance protein. Both the original mutant and the pex4
      deletion strain (Deltapex4) showed a specific defect in import of peroxisomal
      matrix proteins containing a C-terminal targeting signal (PTS1) and of malate
      synthase, whose targeting signal is not yet known. Import of the PTS2 protein
      amine oxidase and the insertion of the peroxisomal membrane proteins Pex3p and
      Pex14p was not disturbed in Deltapex4 cells. The PTS1 protein import defect in
      Deltapex4 cells could be suppressed by overproduction of the PTS1 receptor,
      Pex5p, in a dose-response related manner. In such cells, Pex5p is localized in
      the cytosol and in peroxisomes. The peroxisome-bound Pex5p specifically
      accumulated at the inner surface of the peroxisomal membrane and thus differed
      from Pex5p in wild-type peroxisomes, which is localized throughout the matrix. We
      hypothesize that in H. polymorpha Pex4p plays an essential role for normal
      functioning of Pex5p, possibly in mediating recycling of Pex5p from the
      peroxisome to the cytosol.

PMID- 9649432
TI  - Identification of novel stress-induced genes downstream of chop.
AB  - CHOP (GADD153) is a small nuclear protein that dimerizes avidly with members of
      the C/EBP family of transcription factors. Normally undetectable, it is expressed
      at high levels in cells exposed to conditions that perturb protein folding in the
      endoplasmic reticulum and induce an endoplasmic reticulum stress response. CHOP
      expression in stressed cells is linked to the development of programmed cell
      death and, in some instances, cellular regeneration. In this study,
      representational difference analysis was used to compare the complement of genes
      expressed in stressed wild-type mouse embryonic fibroblasts with those expressed
      in cells nullizygous for chop. CHOP expression, in concert with a second signal,
      was found to be absolutely required for the activation by stress of a set of
      previously undescribed genes referred to as DOCs (for downstream of CHOP). DOC4
      is a mammalian ortholog of a Drosophila gene, Tenm/Odz, implicated in patterning
      of the early fly embryo, whereas DOC6 encodes a newly recognized homolog of the
      actin-binding proteins villin and gelsolin. These results reveal the existence of
      a novel CHOP-dependent signaling pathway, distinct from the known endoplasmic
      reticulum unfolded protein response, which may mediate changes in cell phenotype
      in response to stress.

PMID- 9649433
TI  - PrlA4 prevents the rejection of signal sequence defective preproteins by
      stabilizing the SecA-SecY interaction during the initiation of translocation.
AB  - In Escherichia coli, precursor proteins are translocated across the cytoplasmic
      membrane by translocase. This multisubunit enzyme consists of a preprotein
      binding and ATPase domain, SecA, and the SecYEG complex as the integral membrane
      domain. PrlA4 is a mutant of SecY that enables the translocation of preproteins
      with a defective, or missing, signal sequence. Inner membranes of the prlA4
      strain efficiently translocate Delta8proOmpA, a proOmpA derivative with a non
      functional signal sequence. Owing to the signal sequence mutation, Delta8proOmpA
      binds to the translocase with a lowered affinity and the recognition is not
      restored by the prlA4 SecY. At the ATP-dependent initiation of translocation, the
      binding affinity of SecA for SecYEG is lowered causing the premature loss of
      bound preproteins from the translocase. The prlA4 membranes, however, bind SecA
      with a much higher affinity than the wild-type, and during initiation, the SecA
      and preprotein remain bound at the translocation site allowing an improved
      efficiency of translocation. It is concluded that the prlA4 strain prevents the
      rejection of defective preproteins from the export pathway by stabilizing SecA at
      the SecYEG complex.

PMID- 9649434
TI  - Overlapping functions of components of a bacterial Sec-independent protein export
      pathway.
AB  - We describe the identification of two Escherichia coli genes required for the
      export of cofactor-containing periplasmic proteins, synthesized with signal
      peptides containing a twin arginine motif. Both gene products are homologous to
      the maize HCF106 protein required for the translocation of a subset of lumenal
      proteins across the thylakoid membrane. Disruption of either gene affects the
      export of a range of such proteins, and a complete block is observed when both
      genes are inactivated. The Sec protein export pathway was unaffected, indicating
      the involvement of the gene products in a novel export system. The accumulation
      of active cofactor-containing proteins in the cytoplasm of the mutant strains
      suggests a role for the gene products in the translocation of folded proteins.
      One of the two HCF106 homologues is encoded by the first gene of a four cistron
      operon, tatABCD, and the second by an unlinked gene, tatE. A mutation previously
      assigned to the hcf106 homologue encoded at the tatABCD locus, mttA, lies instead
      in the tatB gene.

PMID- 9649435
TI  - A glutamic finger in the guanine nucleotide exchange factor ARNO displaces Mg2+
      and the beta-phosphate to destabilize GDP on ARF1.
AB  - The Sec7 domain of the guanine nucleotide exchange factor ARNO (ARNO-Sec7) is
      responsible for the exchange activity on the small GTP-binding protein ARF1. ARNO
      Sec7 forms a stable complex with the nucleotide-free form of [Delta17]ARF1, a
      soluble truncated form of ARF1. The crystal structure of ARNO-Sec7 has been
      solved recently, and a site-directed mutagenesis approach identified a
      hydrophobic groove and an adjacent hydrophilic loop as the ARF1-binding site. We
      show that Glu156 in the hydrophilic loop of ARNO-Sec7 is involved in the
      destabilization of Mg2+ and GDP from ARF1. The conservative mutation E156D and
      the charge reversal mutation E156K reduce the exchange activity of ARNO-Sec7 by
      several orders of magnitude. Moreover, [E156K]ARNO-Sec7 forms a complex with the
      Mg2+-free form of [Delta17]ARF1-GDP without inducing the release of GDP. Other
      mutations in ARNO-Sec7 and in [Delta17]ARF1 suggest that prominent hydrophobic
      residues of the switch I region of ARF1 insert into the groove of the Sec7
      domain, and that Lys73 of the switch II region of ARF1 forms an ion pair with
      Asp183 of ARNO-Sec7.

PMID- 9649436
TI  - Stat1 combines signals derived from IFN-gamma and LPS receptors during macrophage
      activation.
AB  - Complete activation of macrophages during immune responses results from
      stimulation with the activating cytokine interferon-gamma (IFN-gamma) and a
      second stimulus, usually a microbial product. Bacterial infection of macrophages,
      or treatment with bacterial lipopolysaccharide (LPS), resulted in rapid Stat1
      phosphorylation on Ser727 (S727) independently of concomitant tyrosine
      phosphorylation. IFN-gamma also caused rapid phosphorylation of S727. In both
      situations, S727 phosphorylation was reduced by pre-treatment of cells with the
      serine kinase inhibitor H7. When macrophages were treated sequentially or
      simultaneously with LPS and IFN-gamma, the pool of molecules phosphorylated on
      both Tyr701 (Y701) and S727 was strongly increased. Consistently, Stat1-dependent
      transcription in response to IFN-gamma was significantly enhanced if the cells
      were pre-treated with bacterial LPS. The relative amount of S727-phosphorylated
      Stat1 in the non-tyrosine phosphorylated fraction was considerably smaller than
      that in the tyrosine-phosphorylated fraction. No evidence was found for an effect
      of S727 phosphorylation on the phosphorylation of Y701 by IFN-gamma. Thus, serine
      and tyrosine phosphorylation of Stat1 are caused independently of each other, but
      the serine kinase may recognize tyrosine-phosphorylated Stat1 preferentially in
      the course of an IFN-gamma response. The data suggest Stat1 to be a convergence
      point for immunological stimuli in a macrophage proinflammatory response.

PMID- 9649437
TI  - Regulation of eosinophil-specific gene expression by a C/EBP-Ets complex and GATA
      1.
AB  - The EOS47 antigen is an early and specific marker of eosinophil differentiation
      in the chicken haematopoietic system. To elucidate the transciptional events
      controlling commitment to the eosinophil lineage, we studied the regulation of
      the eosinophil-specific EOS47 promoter. This promoter is TATA-less, and binds
      trancription factors of the Ets, C/EBP, GATA and Myb families. These sites are
      contained within a 309 bp promoter fragment which is sufficient for specific high
      level transcription in an eosinophil cell line. Co-transfection experiments in
      Q2bn fibroblasts showed cooperative activation of the EOS47 proximal promoter by
      c-Myb, Ets-1/Fli-1, GATA-1 and C/EBPalpha. The Ets-1/Fli-1 and C/EBPalpha
      proteins were the most potent activators, and acted with high synergy through
      juxtaposed binding sites located approximately 60 bp upstream of the
      transcription start site. The Ets-1 and C/EBPalpha proteins were found to
      associate physically via their DNA-binding domains and to bind their combined
      binding site cooperatively. GATA-1 showed biphasic regulation of the EOS47
      promoter, activating at low and repressing at high protein concentrations. These
      results demonstrate combinatorial activation of an eosinophil-specific promoter
      by ubiquitous and lineage-restricted haematopoietic transcription factors. They
      also indicate that direct interactions between C/EBPs and specific Ets family
      members, together with GATA-1, are important for eosinophil lineage
      determination.

PMID- 9649438
TI  - Transcription elongation factor P-TEFb mediates Tat activation of HIV-1
      transcription at multiple stages.
AB  - Tat stimulates human immunodeficiency virus type 1 (HIV-1) transcription
      elongation through recognition of the transactivation response (TAR) RNA stem
      loop structure at the 5' end of nascent viral transcripts. Recently, a human
      transcription elongation factor P-TEFb, consisting of CDK9 kinase, cyclin T and
      other associated factors, has been shown to interact with Tat to restore Tat
      activation in HeLa nuclear extract depleted of P-TEFb. Here, we report the
      purification of a P-TEFb complex fraction containing epitope-tagged wild-type
      CDK9 or kinase-inactive CDK9 and five tightly associated polypeptides. Only wild
      type P-TEFb complex with an active CDK9 kinase was able to hyperphosphorylate the
      C-terminal domain of RNA polymerase II and mediate Tat transactivation in P-TEFb
      depleted HeLa nuclear extract. Tat also stimulated transcription elongation by
      recruitment of the P-TEFb complex to the HIV-1 promoter through a Tat-TAR
      interaction. A possible mechanism for P-TEFb to become associated with polymerase
      elongation complexes and function as a general elongation factor was demonstrated
      by an interaction of P-TEFb with double-stranded RNA molecules through an 87 kDa
      subunit. Finally, P-TEFb was found to interact with and phosphorylate Tat-SF1, a
      Tat cofactor required for Tat transactivation. Our data indicate that the various
      subunits of the human P-TEFb complex may play distinct roles at multiple stages
      to mediate Tat activation of HIV-1 transcription elongation.

PMID- 9649439
TI  - A specialized form of RNA polymerase I, essential for initiation and growth
      dependent regulation of rRNA synthesis, is disrupted during transcription.
AB  - Only a small proportion (<2%) of RNA polymerase I (pol I) from whole-cell
      extracts appeared to be competent for specific initiation at the ribosomal gene
      promoter in a yeast reconstituted transcription system. Initiation-competent pol
      I molecules were found exclusively in salt-resistant complexes that contain the
      pol I-specific initiation factor Rrn3p. Levels of initiation-competent complexes
      in extracts were independent of total Rrn3p content and varied with the growth
      state of the cells. Although extracts from stationary phase cells contained
      substantial amounts of Rrn3p and pol I, they lacked the pol I-Rrn3p complex and
      were inactive in promoter-dependent transcription. Activity was restored by
      adding purified pol I-Rrn3p complex to extracts from stationary phase cells. The
      pol I-Rrn3p complex dissociated during transcription and lost its capacity for
      subsequent reinitiation in vitro, suggesting a stoichiometric rather than a
      catalytic activity in initiation. We propose that the formation and disruption of
      the pol I-Rrn3p complex reflects a molecular switch for regulating rRNA synthesis
      and its growth rate-dependent regulation.

PMID- 9649440
TI  - Molecular mechanism of polyhomeotic activation by Engrailed.
AB  - The Drosophila Engrailed homeoprotein has been shown to activate directly a
      Polycomb-group gene, polyhomeotic, during embryogenesis. The molecular mechanism
      involved in this activation has been studied. Two different types of Engrailed
      binding fragments have been detected within the polyhomeotic locus. The P1 and D1
      fragments contain several 'TTAATTGCAT' motifs, whereas the D2 fragment contains a
      long 'TAAT' stretch to which multiple copies of Engrailed bind cooperatively.
      Another homeodomain-containing protein, Extradenticle, establishes protein
      protein interactions with Engrailed on the D2 fragment. We have shown by CAT
      assays that both types of Engrailed-binding sites (P1 or D1 and D2), as well as
      Extradenticle, are necessary to obtain activation by Engrailed. In vivo, we have
      also shown that normal polyhomeotic expression depends on extradenticle
      expression. Moreover, in the absence of Extradenticle, overexpression of
      Engrailed protein represses polyhomeotic expression.

PMID- 9649441
TI  - Hoxa9 transforms primary bone marrow cells through specific collaboration with
      Meis1a but not Pbx1b.
AB  - Hoxa9, Meis1 and Pbx1 encode homeodomaincontaining proteins implicated in
      leukemic transformation in both mice and humans. Hoxa9, Meis1 and Pbx1 proteins
      have been shown to physically interact with each other, as Hoxa9 cooperatively
      binds consensus DNA sequences with Meis1 and with Pbx1, while Meis1 and Pbx1 form
      heterodimers in both the presence and absence of DNA. In this study, we sought to
      determine if Hoxa9 could transform hemopoietic cells in collaboration with either
      Pbx1 or Meis1. Primary bone marrow cells, retrovirally engineered to overexpress
      Hoxa9 and Meis1a simultaneously, induced growth factor-dependent oligoclonal
      acute myeloid leukemia in <3 months when transplanted into syngenic mice. In
      contrast, overexpression of Hoxa9, Meis1a or Pbx1b alone, or the combination of
      Hoxa9 and Pbx1b failed to transform these cells acutely within 6 months post
      transplantation. Similar results were obtained when FDC-P1 cells, engineered to
      overexpress these genes, were transplanted to syngenic recipients. Thus, these
      studies demonstrate a selective collaboration between a member of the Hox family
      and one of its DNA-binding partners in transformation of hemopoietic cells.

PMID- 9649442
TI  - Processing of a dicistronic small nucleolar RNA precursor by the RNA endonuclease
      Rnt1.
AB  - Small nucleolar RNAs (snoRNAs) are intron encoded or expressed from monocistronic
      independent transcription units, or, in the case of plants, from polycistronic
      clusters. We show that the snR190 and U14 snoRNAs from the yeast Saccharomyces
      cerevisiae are co-transcribed as a dicistronic precursor which is processed by
      the RNA endonuclease Rnt1, the yeast ortholog of bacterial RNase III. RNT1
      disruption results in a dramatic decrease in the levels of mature U14 and snR190
      and in accumulation of dicistronic snR190-U14 RNAs. Addition of recombinant Rnt1
      to yeast extracts made from RNT1 disruptants induces the chase of dicistronic
      RNAs into mature snoRNAs, showing that dicistronic RNAs correspond to functional
      precursors stalled in the processing pathway. Rnt1 cleaves a dicistronic
      transcript in vitro in the absence of other factors, separating snR190 from U14.
      Thus, one of the functions of eukaryotic RNase III is, as for the bacterial
      enzyme, to liberate monocistronic RNAs from polycistronic transcripts.

PMID- 9649443
TI  - Depletion of yeast RNase III blocks correct U2 3' end formation and results in
      polyadenylated but functional U2 snRNA.
AB  - Yeast U2 snRNA is transcribed by RNA polymerase II to generate a single non
      polyadenylated transcript. A temperature-sensitive yeast strain carrying a
      disruption in RNT1, the gene encoding a homolog of RNase III, produces 3'
      extended U2 that is polyadenylated. The U2 3'-flanking region contains a putative
      stem-loop that is recognized and cleaved at two sites by recombinant GST-Rnt1
      protein in vitro. Removal of sequences comprising the stem-loop structure blocks
      cleavage in vitro and mimics the effects of Rnt1 depletion in vivo. Strains
      carrying a U2 gene lacking the Rnt1 cleavage site produce only polyadenylated U2
      snRNA, and yet are not impaired in growth or splicing. The results suggest that
      eukaryotic RNase III may be a general factor in snRNA processing, and demonstrate
      that polyadenylation is not incompatible with snRNA function in yeast.

PMID- 9649444
TI  - The snoRNA box C/D motif directs nucleolar targeting and also couples snoRNA
      synthesis and localization.
AB  - Most small nucleolar RNAs (snoRNAs) fall into two families, known as the box C/D
      and box H/ACA snoRNAs. The various box elements are essential for snoRNA
      production and for snoRNA-directed modification of rRNA nucleotides. In the case
      of the box C/D snoRNAs, boxes C and D and an adjoining stem form a vital
      structure, known as the box C/D motif. Here, we examined expression of natural
      and artificial box C/D snoRNAs in yeast and mammalian cells, to assess the role
      of the box C/D motif in snoRNA localization. The results demonstrate that the
      motif is necessary and sufficient for nucleolar targeting, both in yeast and
      mammals. Moreover, in mammalian cells, RNA is targeted to coiled bodies as well.
      Thus, the box C/D motif is the first intranuclear RNA trafficking signal
      identified for an RNA family. Remarkably, it also couples snoRNA localization
      with synthesis and, most likely, function. The distribution of snoRNA precursors
      in mammalian cells suggests that this coupling is provided by a specific
      protein(s) which binds the box C/D motif during or rapidly after snoRNA
      transcription. The conserved nature of the box C/D motif indicates that its role
      in coupling production and localization of snoRNAs is of ancient evolutionary
      origin.

PMID- 9649445
TI  - lambda bar minigene-mediated inhibition of protein synthesis involves
      accumulation of peptidyl-tRNA and starvation for tRNA.
AB  - Expression of the bacteriophage lambda two-codon, AUG AUA, barI minigene (bar+)
      leads to the arrest of protein synthesis in cells defective in peptidyl-tRNA
      hydrolase (Pth). It has been hypothesized that translation of the bar+ transcript
      provokes premature release and accumulation of peptidyl-tRNA (p-tRNA). Inhibition
      of protein synthesis would then result from either starvation of sequestered tRNA
      or from toxicity of accumulated p-tRNA. To test this hypothesis and to
      investigate the cause of arrest, we used a coupled in vitro transcription
      translation system primed with DNA containing bar+ and the beta-lactamase
      encoding gene of the vector as a reporter. The results show that expression of
      bar+ minigene severely inhibits beta-lactamase polypeptide synthesis by Pth
      defective extracts and partially inhibits synthesis by wild-type extracts.
      Fractions enriched for Pth, or a homogeneous preparation of Pth, prevented and
      reversed bar+-mediated inhibition. A mutant minigene, barA702, which changes the
      second codon AUA (Ile) to AAA (Lys), was also toxic for Pth-defective cells.
      Expression of barA702 inhibited in vitro polypeptide synthesis by Pth-defective
      extracts and, as with bar+, exogenous Pth prevented inhibition. Addition of pure
      tRNALys prevented inhibition by barA702 but not by bar+. Expression of bar+ and
      barA702 led to release and accumulation of p-tRNAIle and p-tRNALys respectively
      but bar+ also induced accumulation of p-tRNALys. Finally, bar+ stimulated
      association of methionine with ribosomes probably as fMet-tRNAfMet and the
      accumulation of methionine and isoleucine in solution as peptidyl-tRNA (p-tRNA).
      These results indicate that minigene-mediated inhibition of protein synthesis
      involves premature release of p-tRNA, misincorporation of amino acyl-tRNA,
      accumulation of p-tRNAs and possibly sequestration of tRNAs.

PMID- 9649446
TI  - Identification of a sequence element immediately upstream of the polypurine tract
      that is essential for replication of simian immunodeficiency virus.
AB  - A short stretch of T-rich sequences immediately upstream of the polypurine tract
      (PPT) is highly conserved in the proviral genomes of human and simian
      immunodeficiency viruses (HIV and SIV). To investigate whether this 'U-box'
      influences SIVmac239 replication, we analyzed the properties of mutants with
      changes in this region of the viral genome. All mutants were either retarded in
      their growth (up to one month delay) or did not replicate detectably in CEMx174
      cells. When U-box mutants did replicate detectably, compensatory changes were
      consistently observed in the viral genome. The most common compensatory change
      was the acquisition of thymidines immediately upstream of the PPT, but marked
      expansion in the length of the PPT was also observed. U-box mutants produced
      transiently by transfection were severely impaired in their ability to produce
      reverse transcripts in infectivity assays. Analysis of transiently produced
      mutant virus revealed no defect in RNA packaging or virus assembly. These results
      identify a new structural element important for an early step in the viral life
      cycle that includes reverse transcription.

PMID- 9649447
TI  - The same two monomers within a MuA tetramer provide the DDE domains for the
      strand cleavage and strand transfer steps of transposition.
AB  - The chemistry of Mu transposition is executed within a tetrameric form of the Mu
      transposase (MuA protein). A triad of DDE (Asp, Asp35Glu motif) residues in the
      central domain of MuA (DDE domain) is essential for both the strand cleavage and
      strand transfer steps of transposition. Previous studies had suggested that
      complete Mu transposition requires all four subunits in the MuA tetramer to carry
      an active DDE domain. Using a mixture of MuA proteins with either wild-type or
      altered att-DNA binding specificities, we have now designed specific arrangements
      of MuA subunits carrying the DDE domain. From analysis of the abilities of
      oriented tetramers to carry out DNA cleavage and strand transfer from supercoiled
      DNA, a new picture of the disposition of DNA and protein partners during
      transposition has emerged. For DNA cleavage, two subunits of MuA located at attL1
      and attR1 (sites that undergo cleavage) provide DDE residues in trans. The same
      two subunits contribute DDE residues for strand transfer, also in trans. Thus,
      only two active DDE+ monomers within the tetramer carry out complete Mu
      transposition. We also show that when the attR1-R2 arrangement used on
      supercoiled substrates is tested for cleavage on linear substrates, alternative
      chemically competent DNA-protein associations are produced, wherein the
      functional DDE subunits are positioned at R2 rather than at R1.

PMID- 9649449
TI  - CFTR: from scientific inquiry to clinical remedy.

PMID- 9649448
TI  - DNA ligase I is recruited to sites of DNA replication by an interaction with
      proliferating cell nuclear antigen: identification of a common targeting
      mechanism for the assembly of replication factories.
AB  - In mammalian cells, DNA replication occurs at discrete nuclear sites termed
      replication factories. Here we demonstrate that DNA ligase I and the large
      subunit of replication factor C (RF-C p140) have a homologous sequence of
      approximately 20 amino acids at their N-termini that functions as a replication
      factory targeting sequence (RFTS). This motif consists of two boxes: box 1
      contains the sequence IxxFF whereas box 2 is rich in positively charged residues.
      N-terminal fragments of DNA ligase I and the RF-C large subunit that contain the
      RFTS both interact with proliferating cell nuclear antigen (PCNA) in vitro.
      Moreover, the RFTS of DNA ligase I and of the RF-C large subunit is necessary and
      sufficient for the interaction with PCNA. Both subnuclear targeting and PCNA
      binding by the DNA ligase I RFTS are abolished by replacement of the adjacent
      phenylalanine residues within box 1. Since sequences similar to the RFTS/PCNA
      binding motif have been identified in other DNA replication enzymes and in
      p21(CIP1/WAF1), we propose that, in addition to functioning as a DNA polymerase
      processivity factor, PCNA plays a central role in the recruitment and stable
      association of DNA replication proteins at replication factories.

PMID- 9649450
TI  - Image of the month. Esophageal diverticulum.

PMID- 9649451
TI  - Colonoscopic screening in first-degree relatives of patients with 'sporadic'
      colorectal cancer: a case-control study. The Association Nationale des
      Gastroenterologues des Hopitaux and Registre Bourguignon des Cancers Digestifs
      (INSERM CRI 9505)
AB  - BACKGROUND & AIMS: A screening policy has not been well defined in first-degree
      relatives of patients with sporadic colorectal cancer. This study estimated the
      risk of colorectal adenoma in a cohort of individuals with only 1 affected first
      degree relative. METHODS: A total of 476 first-degree relatives (age, 40-74
      years) of 195 patients with sporadic colorectal cancer were offered a
      colonoscopy. Each examined relative was matched with 2 controls for age, sex,
      symptoms, and center. The prevalence of colorectal adenomas was compared using a
      multiple logistic regression analysis. RESULTS: In 185 relatives, odds ratios
      were 1.5 (95% confidence interval [CI], 1.0-2.4) for adenomas, 2.5 for large
      adenomas (95% CI, 1.1-5.4), 1.2 for small adenomas (95% CI, 0.7-1.9), and 2.6
      (95% CI, 1.3-5.1) for high-risk adenomas (> or = 1 cm in size and/or with a
      villous component). The prevalence of high-risk adenomas in relatives was higher
      when the index patient was younger than 65 years, was male, and had distal rather
      than proximal cancer. CONCLUSIONS: Subjects with only 1 affected first-degree
      relative are at increased risk for developing large adenomas.

PMID- 9649452
TI  - Cruveilhier of la maladie de Cruveilhier.

PMID- 9649453
TI  - Adenoma characteristics at first colonoscopy as predictors of adenoma recurrence
      and characteristics at follow-up. The Polyp Prevention Study Group.
AB  - BACKGROUND & AIMS: All patients with colorectal adenomas may not require
      identical follow-up. We aimed to determine if adenoma characteristics at initial
      colonoscopy could predict adenoma recurrence or characteristics at follow-up.
      METHODS: The number of adenomas and the size, type, and degree of atypia in 479
      patients in a polyp prevention trial were evaluated as predictors of the same
      characteristics at follow-up using odds ratios (ORs) with 95% confidence
      intervals (CIs). Multiple logistic regression analysis was performed to determine
      if several baseline characteristics were simultaneously associated with outcome.
      RESULTS: Although several characteristics were significant predictors of
      recurrence univariately, by multivariate analysis, multiple adenomas at follow-up
      were more likely when patients had > or = 3 baseline adenomas (OR, 2.25; 95% CI,
      1.20-4.21) or at least 1 tubulovillous adenoma (OR, 2.12; 95% CI, 1.12-4.02). No
      specific characteristic was associated with recurrence of high-risk polyps (> or
      = 1 cm, villous, severe atypia). Seventy percent of patients with 1 or 2 baseline
      adenomas had no recurrence, and only 3.3% had any adenomas of clinical concern.
      CONCLUSIONS: Number and type of baseline adenomas predict recurrent adenomas, but
      the recurrence is rarely of clinical concern. Patients with 1 or 2 tubular
      adenomas constitute a low-risk group for whom follow-up might be extended beyond
      3 years.

PMID- 9649454
TI  - Anti-p53 antibodies in patients with Barrett's esophagus or esophageal carcinoma
      can predate cancer diagnosis.
AB  - BACKGROUND & AIMS: We previously discovered anti-p53 antibodies predating a
      cancer diagnosis in subjects at increased risk for liver, lung, breast, and
      prostate cancer. Recently, we reported a significant correlation (P < 0.017)
      between p53 antibodies and p53 mutations in patients with late-stage esophageal
      carcinoma. Because others have reported p53 mutations and overexpression of p53
      protein in Barrett's esophagus, we studied p53 antibodies in plasma of 88
      serially endoscoped patients: 36 with Barrett's metaplasia, 23 with esophageal
      squamous cell carcinoma, 10 with esophageal adenocarcinoma, and 19 with
      esophagitis or normal esophagus. METHODS: We used enzyme immunoassay,
      immunoblotting, and immunoprecipitation assays for p53 antibodies; polymerase
      chain reaction, denaturant gradient gel electrophoresis, and sequencing for p53
      mutations; and immunohistochemistry for p53 protein. RESULTS: p53 antibodies were
      detected in 4 patients with Barrett's esophagus, including 1 with dysplasia that
      later progressed to adenocarcinoma, and in 10 cancer patients (P = 0.002) (8
      squamous and 2 adenocarcinoma), 2 of whom (1 squamous, 1 adenocarcinoma) had
      antibodies before cancer was diagnosed. Other patient groups were too small for
      informative statistical analysis. Six antibody-positive cancer patients had p53
      mutations, whereas 2 patients with cancer and 1 with Barrett's esophagus with
      antibodies had p53 protein overexpressed in esophageal tissues. CONCLUSIONS:
      Patients with Barrett's esophagus and esophageal cancer can develop p53
      antibodies that may predate the clinical diagnosis of malignancy.

PMID- 9649455
TI  - Oral beclomethasone dipropionate for treatment of intestinal graft-versus-host
      disease: a randomized, controlled trial.
AB  - BACKGROUND & AIMS: Beclomethasone dipropionate (BDP), a topically active steroid,
      seemed to be an effective treatment for intestinal graft-versus-host disease
      (GVHD) in a phase I study. The aim of this study was to compare the effectiveness
      of oral BDP to that of placebo capsules in treatment of intestinal GVHD. METHODS:
      Sixty patients with anorexia and poor oral intake because of intestinal GVHD were
      randomized to receive prednisone (1 mg.kg-1.day-1) plus either oral BDP (8
      mg/day) or placebo capsules. Initial responders who were eating at least 70% of
      caloric needs at evaluation on day 10 continued to take study capsules for an
      additional 20 days while the prednisone dose was rapidly tapered. The primary end
      point was the frequency of a durable treatment response at day 30 of treatment.
      RESULTS: The initial treatment response at day 10 was 22 of 31 (71%) in the
      BDP/prednisone group vs. 16 of 29 (55%) for the placebo/prednisone group. The
      durable treatment response at day 30 was 22 of 31 (71%) vs. 12 of 29 (41%),
      respectively (P = 0.02). CONCLUSIONS: The combination of oral BDP capsules and
      prednisone was more effective than prednisone alone in treating intestinal GVHD.
      Oral BDP allowed prednisone doses to be rapidly tapered without recurrent
      intestinal symptoms.

PMID- 9649456
TI  - Effect of a low-impact exercise program on bone mineral density in Crohn's
      disease: a randomized controlled trial.
AB  - BACKGROUND & AIMS: Physical exercise increases bone mineral density (BMD) in
      healthy young adults and slows the rate of bone loss in later life. The aim of
      this randomized controlled trial was to investigate the effect of exercise on BMD
      in patients with Crohn's disease. METHODS: A total of 117 patients with Crohn's
      disease were randomized to a control group or a low-impact exercise program of
      increasing intensity. BMD (g/cm2) was measured at baseline and 12 months at the
      hip and spine (L2-L4) by dual energy x-ray absorptiometry. RESULTS:
      Nonsignificant gains in BMD occurred at the hip and spine in the exercise group
      compared with controls (P > 0.05). In fully compliant patients, BMD increased by
      3.54% (7.95%) at the femoral neck, 2.97% (7.7%) at the spine, 4.1% (10.26%) at
      Ward's triangle, and 7.77% (8.2%) at the greater trochanter. Compared with
      controls, gain in BMD at the greater trochanter was statistically significant
      (difference in means, 4.67; 95% confidence interval, 0.86-8.48; P = 0.02).
      Increases in BMD were significantly related to the number of exercise sessions
      completed (femoral neck; r = 0.28; 95% confidence interval, 0.10-0.45; P = 0.04).
      CONCLUSIONS: Progressive low-impact exercise is a potentially effective method of
      increasing BMD in Crohn's disease. If sustained, the increases in BMD may reduce
      the risk of osteoporotic fracture.

PMID- 9649457
TI  - The clinical and economic value of a short course of omeprazole in patients with
      noncardiac chest pain.
AB  - BACKGROUND & AIMS: Evaluation of new patients with noncardiac chest pain (NCCP)
      may require a variety of costly tests. The aim of this study was to evaluate the
      efficacy of the omeprazole test (OT) in diagnosing gastroesophageal reflux (GERD)
      in patients with NCCP and estimate the potential cost savings of this strategy
      compared with conventional diagnostic evaluations. METHODS: Thirty-nine patients
      referred by cardiologists were enrolled. Baseline symptoms were recorded, and the
      patients were randomized to either placebo or omeprazole (40 mg AM and 20 mg PM)
      groups for 7 days. Patients were crossed over to the other arm after a washout
      period and repeat baseline symptom assessment. All patients underwent 24-hour
      esophageal pH monitoring and upper endoscopy before randomization. RESULTS:
      Thirty-seven patients (94.9%) completed the study. Twenty-three (62.2%) were
      classified as GERD positive and 14 as GERD negative. Eighteen (78%) GERD-positive
      patients and 2 (14%) GERD-negative patients had a positive OT (P < 0.01),
      yielding a sensitivity of 78.3% (95% confidence interval, 61.4-95.1) and
      specificity of 85.7% (95% confidence interval, 67.4-100). Economic analysis
      showed that the OT saves $573 per average patient evaluated and results in a 59%
      reduction in the number of diagnostic procedures. CONCLUSIONS: The OT is
      sensitive and specific for diagnosing GERD in patients with NCCP. This strategy
      results in significant cost savings and decreased use of diagnostic tests.

PMID- 9649458
TI  - The seroprevalence of cagA-positive Helicobacter pylori strains in the spectrum
      of gastroesophageal reflux disease.
AB  - BACKGROUND & AIMS: The role of Helicobacter pylori in the pathogenesis of
      gastroesophageal reflux disease (GERD) is unknown. We determined the prevalence
      of cagA-positive (cagA+) H. pylori strains in patients with GERD or its
      complications compared with controls of similar age. METHODS: A total of 153
      consecutive patients with GERD, Barrett's esophagus, and Barrett's esophagus
      complicated by dysplasia or adenocarcinoma were compared with 57 controls who
      underwent upper endoscopy for reasons other than GERD. H. pylori infection and
      CagA antibody status were determined by histology and enzyme-linked immunosorbent
      assay. RESULTS: H. pylori prevalence was lower (34%) in patients with GERD and
      its sequelae than in the control group (45.6%)(P = 0.15). Regardless of the
      group, increasing age was associated with higher prevalence of H. pylori (P =
      0.003). When compared with controls (42.3%), the prevalence of cagA+ H. pylori
      strains decreased (P = 0.008) in patients with more severe complications of GERD
      (GERD, 36.7% [nonerosive GERD, 41.2%; erosive GERD, 30.8%]; Barrett's esophagus,
      13.3%; and Barrett's with adenocarcinoma/dysplasia, 0%). CONCLUSIONS: Prevalence
      of H. pylori in patients with GERD and its sequelae was lower but not
      significantly different than that of a control group. However, patients carrying
      cagA+ strains of H. pylori may be protected against the complications of GERD,
      especially Barrett's esophagus and its associated dysplasia and adenocarcinoma.

PMID- 9649459
TI  - Clinical relevance of the cagA, vacA, and iceA status of Helicobacter pylori.
AB  - BACKGROUND & AIMS: Clinical outcome of Helicobacter pylori infection may be
      associated with specific virulence-associated bacterial genotypes. The aim of
      this study was to assess the relationships between H. pylori cagA, vacA, and iceA
      status and severity of disease. METHODS: Gastric biopsy specimens from 94
      patients in The Netherlands were analyzed by polymerase chain reaction and
      reverse hybridization. RESULTS: cagA was present in 63 (67%) of 94 cases and was
      associated with peptic ulcer disease (P = 0.0019). vacA geno-types s1a/m1,
      s1b/m2, s1b/m1, s1b/m2, and s2/m2 were found in 36.2%, 23.4%, 2.1%, 5.3%, and
      20.2%, respectively. Ten isolates (10.6%) contained multiple vacA genotypes. The
      presence of peptic ulcers was associated with type s1 strains (P = 0.0006) but
      not with the m type (P = 0.2035). cagA and vacA s1 were strongly associated (P <
      10(-5)). iceA1 was found in 53 (56.4%) and iceA2 in 25 (26.6%) of the 94 cases.
      In 14 isolates (14.9%), both iceA alleles were found, and 2 (2.1%) were negative
      for both iceA1 and iceA2. iceA1 was also associated with peptic ulcer disease (P
      = 0.0042). The iceA allelic type was independent of the cagA and vacA status.
      CONCLUSIONS: vacA s1, cagA, and iceA1 are markers of H. pylori strains that are
      more likely to lead to ulcer disease.

PMID- 9649460
TI  - The effect of tacrolimus (FK506) on intestinal barrier function and cellular
      energy production in humans.
AB  - BACKGROUND & AIMS: The maintenance of the intestinal mucosal barrier may be
      energy dependent. Tacrolimus is a potent immunosuppressive drug that decreases
      mitochondrial adenosine triphosphate production and increases intestinal
      permeability in animals. METHODS: Twelve liver graft recipients receiving
      tacrolimus, 9 healthy volunteers, and 5 liver graft recipients not receiving
      immunosuppression underwent a combined absorption-permeability-mitochondrial
      function test using 5 g lactulose, 1 g L-rhamnose, 0.5 g D-xylose, 0.2 g 3-O
      methyl-D-glucose, 1 mg/kg 2-keto[1-13C]isocaproic acid ([13C]KICA), and 20 mg/kg
      L-leucine. The respiratory quotient and resting energy expenditure were measured
      by indirect calorimetry. Tacrolimus pharmacokinetic profiles and levels of
      endotoxin and IgM and IgG endotoxin core antibodies were determined. RESULTS:
      Tacrolimus inhibited the decarboxylation of [13C]KICA, the resting energy
      expenditure, and the respiratory quotient in an exposure-dependent manner,
      suggesting an inhibition of mitochondrial respiration. Tacrolimus inhibited
      intestinal absorptive capacity in an exposure-dependent manner. Tacrolimus
      treated patients had an increased intestinal permeability and significantly
      higher endotoxin levels compared with healthy volunteers. CONCLUSIONS: Tacrolimus
      inhibits cellular energy production in humans at clinically relevant doses. This
      is associated with an increased intestinal permeability, endotoxemia, and an
      impaired intestinal absorptive capacity.

PMID- 9649461
TI  - Colonocyte differentiation is associated with increased expression and altered
      distribution of protein kinase C isozymes.
AB  - BACKGROUND & AIMS: Colon cancer cells express reduced levels of protein kinase C
      (PKC). This study examines the regulation of PKC isozymes in normal colonic
      epithelium, as a basis for understanding the significance of alterations in this
      enzyme system in colon carcinogenesis. METHODS: The expression and localization
      of PKC isozymes in mouse and rat colonocytes at different developmental stages
      were determined using a combined morphological and biochemical approach. PKC
      alpha expression was compared in colonic adenocarcinomas and adjacent normal
      mucosa by immunoblot analysis. RESULTS: Mouse and rat colonocytes express PKC
      alpha, beta II, delta, epsilon, and zeta. Relatively low levels of these isozymes
      were detected in proliferating cells of the crypt base, predominantly in the
      cytosolic compartment. Coincident with colonocyte growth arrest/differentiation,
      PKC isozyme expression markedly increased in both the cytosolic and, more
      significantly, in the membrane/cytoskeletal fraction. Colonic tumors express
      reduced levels of PKC alpha, an isozyme that has been implicated in negative
      control of intestinal cell growth. CONCLUSIONS: These findings are supportive of
      a role for certain PKC isozyme(s) in signaling pathways mediating postmitotic
      events in colonocytes in situ, and suggest that diminished activity of these
      pathway(s) may contribute to the alterations in growth control/differentiation
      associated with colonic neoplasia.

PMID- 9649462
TI  - Three distinct messenger RNA distribution patterns in human jejunal enterocytes.
AB  - BACKGROUND & AIMS: The importance of messenger RNA (mRNA) localization in human
      enterocytes is poorly understood. Previous studies from our laboratory have
      indicated that mRNAs are asymmetrically distributed in human intestinal
      epithelial cells, but in general colocalized with their encoded proteins. The aim
      of this study was to characterize, in human enterocytes, mRNA localization
      patterns of three genes with distinctly different functions. METHODS: mRNA
      distribution was determined by in situ hybridization with digoxigenin-labeled RNA
      probes in tissue sections of human jejunum. RESULTS: The mRNA for villin, a well
      characterized microvillus cytoskeletal protein, was sorted to the basal region of
      the enterocyte. The mRNA for human sodium glucose cotransporter 1 was localized
      to the apical region, and the mRNA for human liver fatty acid-binding protein was
      distributed diffusely in the cytoplasm. CONCLUSIONS: The three distinct mRNA
      distribution patterns suggest that active mRNA sorting mechanisms exist in human
      enterocytes. This study also reveals for the first time that dichotomies may
      occur between the distribution patterns of sorted mRNAs and their encoded
      proteins.

PMID- 9649463
TI  - Comparison of the signal transduction pathways activated by gastrin in
      enterochromaffin-like and parietal cells.
AB  - BACKGROUND & AIMS: Gastrin stimulates acid secretion from parietal cells and
      histamine release from enterochromaffin-like (ECL) cells through identical
      gastrin receptors. However, gastrin has been shown to have a trophic effect only
      on ECL cells. The aim of this study was to compare gastrin-induced signal
      transduction pathways in the ECL and parietal cells of Mastomys natalensis, an
      African rodent. METHODS: Both ECL and parietal cells were isolated from the
      gastric mucosa of M. natalensis, and intracellular signal transduction events in
      response to gastrin were investigated. RESULTS: Gastrin elicited histamine
      release from ECL cells and acid secretion from parietal cells in association with
      enhanced inositol phospholipid turnover. Although gastrin increased [3H]thymidine
      incorporation into ECL cells, it had no effect on parietal cells. Moreover,
      tyrosine phosphorylation and activation of mitogen-activated protein (MAP) kinase
      as well as c-fos and c-jun gene expression were augmented only in ECL cells. In
      addition, gastrin increased the formation of guanosine triphosphate-Ras with a
      simultaneous decrease in guanosine diphosphate-Ras levels in ECL but not in
      parietal cells. CONCLUSIONS: Although gastrin receptors are present in both ECL
      and parietal cells, they activate the Ras-MAP kinase pathway only in ECL cells.

PMID- 9649464
TI  - Cyclooxygenase 1 contributes to inflammatory responses in rats and mice:
      implications for gastrointestinal toxicity.
AB  - BACKGROUND & AIMS: Selective inhibitors of cyclooxygenase (COX)-2 are being
      developed as gastrointestinal-sparing anti-inflammatory drugs based on the
      premise that this isoform is solely responsible for prostaglandin synthesis at
      sites of inflammation, whereas COX-1 produces prostaglandins important for
      maintenance of mucosal integrity. We investigated the relationship between
      suppression of inflammation by COX-2 inhibitors (NS-398, nimesulide, DuP697, and
      etodolac) and their effects on gastric prostaglandin synthesis. METHODS: Effects
      of pretreatment of rats with drugs with a range of in vitro selectivity for COX-2
      vs. COX-1 on carrageenan-induced paw inflammation were assessed, along with
      extent of suppression of COX-1 and COX-2. The role of COX-1 in inflammation was
      also assessed in COX-2-deficient mice. RESULTS: Significant anti-inflammatory
      effects were only observed at doses of the drugs that inhibited COX-1. At these
      doses, the drugs also significantly suppressed gastric prostaglandin synthesis
      and elicited gastric mucosal erosions. The degree of suppression of prostaglandin
      synthesis at the site of inflammation correlated significantly with inhibition of
      COX-1 but not COX-2. CONCLUSIONS: COX-1 makes an important contribution to
      inflammatory responses. To achieve desirable anti-inflammatory effects, COX-2
      inhibitors needed to be given at doses in which selectivity was lost, leading to
      suppression of gastric prostaglandin synthesis and to mucosal injury.

PMID- 9649465
TI  - Vegetative infection of transjugular intrahepatic portosystemic shunts.
AB  - BACKGROUND & AIMS: The occurrence of and the clinical picture of infection of
      transjugular intrahepatic portosystemic shunts (TIPS) has not been described
      previously. We describe the clinical features, associated pathogens, results of
      treatment of a previously unreported complication of TIPS, and primary infection
      of TIPS occurring after formation of the neointima. METHODS: Patients with TIPS
      and fever were evaluated to exclude other sources of infection. The diagnosis was
      based on the occurrence of fever with positive blood cultures and either a
      thrombus or vegetations on the stent or persistent bacteremia in a patient with a
      TIPS and no other detectable source of infection despite an extensive search.
      RESULTS: Eight patients met diagnostic criteria. Two of 8 cases occurred within
      10 days of TIPS manipulation despite antibiotic administration before the
      procedure. The clinical features included fever (8 patients), tender hepatomegaly
      (5 of 8), hypoxemia (2 of 8), septic pulmonary emboli (1 of 8), septic shock (2
      of 8), neutrophilia (5 of 8), and subsequent development of necrotizing fasciitis
      (1 of 8). Blood cultures were positive in all cases. The organisms included oral
      and enteric aerobic gram-negative bacteria in 7 of 8 patients and Candida in 1
      patient. All 8 responded to administration of antibiotics. Two patients died of
      myocardial infarction and alcoholic hepatitis, respectively. CONCLUSIONS:
      Infective endotipsitis is an uncommon complication of TIPS. Recognition of its
      clinical features will facilitate diagnosis. Most patients responded to
      antibiotic therapy.

PMID- 9649466
TI  - Propranolol plus prazosin compared with propranolol plus isosorbide-5-mononitrate
      in the treatment of portal hypertension.
AB  - BACKGROUND & AIMS: The association of prazosin to propranolol enhances the
      decrease in portal pressure but may cause hypotension and sodium retention. The
      aim of this study was to compare the portal pressure reduction and safety of the
      combination of propranolol plus prazosin with that of propranolol plus isosorbide
      5-mononitrate (ISMN). METHODS: Fifty-six portal-hypertensive cirrhotics received
      randomly propranolol plus prazosin (n = 28) or propranolol plus ISMN (n = 28)
      orally for 3 months. Hemodynamics and liver and renal function were assessed at
      baseline and after 3 months. RESULTS: Propranolol plus prazosin caused a greater
      reduction in hepatic venous pressure gradient (HVPG) than propranolol plus ISMN (
      24.2% +/- 11% vs. -16.1% +/- 11%; P < 0.01). A reduction in HVPG of > 20% was
      significantly more frequent in the propranolol plus prazosin group than in the
      propranolol plus ISMN group (85% vs. 53%; P < 0.05). Neither treatment modified
      hepatic blood flow, quantitative liver function test results, glomerular
      filtration rate, plasma renin activity, or plasma aldosterone level. Side effects
      occurred in 13 patients receiving propranolol plus prazosin compared with 7
      receiving propranolol plus ISMN (P = 0.16). CONCLUSIONS: Propranolol plus
      prazosin has a greater portal pressure-lowering effect than propranolol plus
      ISMN. Both therapies were safe for liver and renal function. However, the
      combination of propranolol plus prazosin caused a greater decrease in arterial
      pressure and was less well tolerated than propranolol plus ISMN.

PMID- 9649467
TI  - Bile lithogenicity and gallbladder emptying in patients with microlithiasis:
      effect of bile acid therapy.
AB  - BACKGROUND & AIMS: Biliary cholesterol supersaturation, rapid nucleation of
      cholesterol, and altered gallbladder motility are prerequisite for gallstone
      formation. However, the pathogenesis of microlithiasis is not clear. The aim of
      this study was to determine the abnormalities of gallbladder emptying and bile
      composition in patients with microlithiasis. METHODS: Nucleation time,
      cholesterol saturation index (CSI), and gallbladder emptying were studied in
      patients with microlithiasis (n = 10), patients with gallstones (n = 10), and
      healthy volunteers (n = 10). Bile analysis was repeated in 6 patients with
      microlithiasis treated with ursodeoxycholic acid (UDCA) for 8 weeks. RESULTS:
      Nucleation time was shorter in patients with microlithiasis and those with
      gallstones than in healthy volunteers (P < 0.0001). Patients with microlithiasis
      had longer nucleation time than those with gallstones (P < 0.001). There was no
      difference in cholesterol levels and CSI in gallstone and microlithiasis
      patients. However, healthy volunteers had lower cholesterol levels (P < 0.01) and
      CSI (P < 0.01). Patients with microlithiasis had prolongation of nucleation time
      (P < 0.001) and lowering of CSI (P < 0.001) after UDCA therapy. Gallbladder
      ejection fraction was higher in microlithiasis patients than in gallstone
      patients (P < 0.01) but lower than in healthy volunteers (P < 0.01). CONCLUSIONS:
      Patients with microlithiasis have longer nucleation time and better gallbladder
      emptying than patients with gallstones. Bile abnormalities can be successfully
      corrected with UDCA therapy in patients with microlithiasis.

PMID- 9649468
TI  - Biliary secretory immunoglobulin A is a major constituent of the new group of
      cholesterol crystal-binding proteins.
AB  - BACKGROUND & AIMS: Recently we described a new group of lectin-bound biliary
      proteins that bind to cholesterol crystals, modify crystal morphology, and
      inhibit cholesterol crystallization. The aim of the current study was to
      characterize and identify individual members of this group of cholesterol crystal
      binding proteins. METHODS: Crystal-binding proteins were purified from human
      gallbladder bile by lectin affinity chromatography and preparative gel
      electrophoresis. Purified crystal-binding proteins were characterized by using
      cholesterol crystal-growth assays, immunoblotting, and amino acid analysis. For
      comparison, identified biliary proteins were isolated from gallbladder bile by
      lectin affinity and immunoaffinity chromatography. RESULTS: The individual
      crystal-binding proteins with molecular weights of 74, 63, and 28 kilodaltons
      inhibited cholesterol crystallization in a dose-dependent manner (2.5-10
      micrograms/mL). Immunoblotting with specific antibodies and N-terminal amino acid
      sequences revealed that the 74-kilodalton crystal-binding protein is the
      secretory component, the 63-kilodalton protein is the heavy chain, and the 28
      kilodalton protein is the light chain of human secretory immunoglobulin (Ig) A.
      Isolated biliary IgA showed a potent inhibitory effect on cholesterol
      crystallization in model bile even at levels less than physiological
      concentrations (1-100 micrograms/mL). CONCLUSIONS: Biliary secretory IgA is a
      major constituent of the previously described group of cholesterol crystal
      binding proteins. Crystal-binding IgA may be an important modulator of crystal
      agglomeration into stones and stone growth in vivo.

PMID- 9649469
TI  - Three-dimensional structure of the major autoantigen in primary biliary
      cirrhosis.
AB  - BACKGROUND & AIMS: Primary biliary cirrhosis (PBC) is a chronic cholestatic liver
      disease characterized by the presence of antimitochondrial autoantibodies in
      patients' serum. The major autoantigen, recognized by antibodies from > 95% of
      patients with PBC, has been identified as the E2 component (E2p) of the pyruvate
      dehydrogenase multienzyme complex. Immunodominant sites on E2p have been
      localized to the inner of the two lipoyl domains, where the essential cofactor
      lipoic acid is attached covalently. The aim of this study was to determine the
      three-dimensional structure of the inner lipoyl domain of human E2p. METHODS: The
      domain was expressed in Escherichia coli; after purification, its structure was
      analyzed using nuclear magnetic resonance spectroscopy. RESULTS: The structure of
      the lipoyl domain from human E2p was determined, and the implications of the
      structure for autoimmune recognition were assessed. CONCLUSIONS: Knowledge of the
      structure further defines the major epitope and may help in the design of antigen
      specific immunotherapy for treatment of PBC.

PMID- 9649470
TI  - Altered biosynthesis of leukotrienes and lipoxins and host defense disorders in
      patients with cirrhosis and ascites.
AB  - BACKGROUND & AIMS: Advanced cirrhosis is associated with impaired leukocyte
      function, but the mechanism underlying this host defense alteration is unknown.
      The aim of this study was to investigate the lipoxygenase pathway of arachidonic
      acid metabolism and its influence in leukocyte trafficking in patients with
      cirrhosis and ascites. METHODS: Neutrophils (polymorphonuclear leukocytes [PMN])
      were isolated from patients with cirrhosis and ascites and healthy subjects, and
      5-lipoxygenase (5-LO) messenger RNA levels and 5-LO-derived products were
      measured. The effect of leukotrienes (LT) and lipoxins (LX) on PMN adhesion and
      migration was also assessed. RESULTS: PMN from patients with cirrhosis showed
      increased 5-LO messenger RNA expression. However, in vitro generation of LTB4,
      cysteinyl-containing LT and LX was significantly decreased in cirrhotic patients.
      Interestingly, a close relationship between the activity of the renin-angiotensin
      system and LXA4 biosynthesis was observed both in vitro and in vivo. PMN isolated
      from cirrhotic patients with ascites showed significantly decreased adhesion and
      migration in response to LTB4. LXA4 did not provoke PMN adhesion and migration,
      but rather abrogated the differences between control and cirrhotic PMN. Cirrhotic
      monocytes showed marked impairment in adherence to laminin when stimulated with
      either LTB4 or LXA4. CONCLUSIONS: These results show the existence of altered
      biosynthesis of LT and LX and defective response to these lipoxygenase products
      in leukocytes from patients with cirrhosis and ascites. This abnormality may be
      relevant to the pathogenesis of host defense disorders in chronic liver disease.

PMID- 9649471
TI  - Role of cytokines in ethanol-induced cytotoxicity in vitro in Hep G2 cells.
AB  - BACKGROUND & AIMS: As shown previously by us, ethanol (EtOH) causes time- and
      concentration-dependent reduction in cytoviability. Tauroursodeoxycholic acid
      (TUDCA) and ursodeoxycholic acid (UDCA) were shown to reduce cytotoxicity. Long
      term EtOH exposure leads to immunoregulatory and detoxification impairment. This
      study aimed to determine the relationship between cytokine (interleukin [IL]-1
      alpha and IL-6 and tumor necrosis factor [TNF]-alpha) production and expression,
      glutathione (GSH) status, and EtOH-induced cytotoxicity on Hep G2 cells. METHODS:
      Cells were incubated with 80 mmol/L EtOH or alpha-minimal essential medium
      (control) in the presence or absence of 50 mumol/L TUDCA or UDCA. Cytokine
      release was quantitated by enzyme-linked immunosorbent assay. Cytokine expression
      was measured by reverse-transcription polymerase chain reaction. GSH content was
      determined in both the cytosolic and mitochondrial fractions. RESULTS: After 24
      hours of EtOH exposure, the release of IL-1 alpha doubled, that of IL-6 increased
      10 times, and that of TNF-alpha increased 3.5 times. Cytokine expression was up
      regulated compared with control for IL-1 alpha (42%), IL-6 (26%), and TNF-alpha
      (52%). Addition of 50 mumol/L TUDCA or UDCA reduced cytokine release and
      expression. TNF-alpha increased cytotoxicity by 18%. Anti-TNF-alpha antibody
      almost abolished it. EtOH depleted mGSH levels by 55% (P < 0.001). TUDCA
      replenished them by 88%. CONCLUSIONS: EtOH up-regulated expression of cytokines
      in Hep G2 cells is down-regulated by bile acids. Increased amounts of TNF-alpha
      and depletion in both cytosolic and mitochondrial GSH contribute to EtOH
      cytotoxicity. Bile acids prevent toxicity.

PMID- 9649472
TI  - Transjugular intrahepatic portosystemic shunt for bleeding angiodysplasia-like
      lesions in portal-hypertensive colopathy.
AB  - Portal-hypertensive colopathy has attracted interest in recent years because such
      lesions can cause life-threatening hemorrhage. In contrast to upper
      gastrointestinal bleeding from varices, there is no established therapy for
      bleeding from angiodysplasia-like lesions. This case report describes the first
      successful use of transjugular intrahepatic portosystemic shunt (TIPS) for long
      term control of bleeding from angiodysplasia-like colonic lesions in a patient
      with cirrhosis caused by chronic hepatitis B infection. During an 18-month course
      after TIPS, angiodysplasia-like lesions disappeared without any further evidence
      of recurrent hematochezia. TIPS may be helpful as second-line treatment in
      patients with recurrent portal-hypertensive bleeding from colonic angiodysplasia
      like lesions who do not tolerate or are unresponsive to treatment with beta
      adrenergic blockers.

PMID- 9649473
TI  - Overexpression of an unstable intrinsic factor-cobalamin receptor in Imerslund
      Grasbeck syndrome.
AB  - Two sisters with Imerslund-Grasbeck syndrome who presented with clinical features
      of cobalamin deficiency are described. Intrinsic factor-cobalamin receptor (IFCR)
      activity and protein levels were determined in ileal biopsy specimens by using
      radioisotope assay and immunoblotting, respectively. IFCR activities in ileal
      homogenates expressed as femtomoles of ligand binding per milligram of protein
      were 38 +/- 4 in control tissue, 494 +/- 24 in patient 1, and 94 +/- 7 in patient
      2. However, when assayed in the presence of IFCR antiserum, the ligand binding
      was inhibited by > 90% in both normal control and the patients with Imerslund
      Grasbeck syndrome. Immunoblotting of total membranes from the biopsy specimen of
      these 2 patients failed to detect an immunoreactive band of molecular mass of 185
      kilodaltons. These findings are at variance with reports of decreased IFCR
      activity and indicate a new phenotype in which an active but an unstable receptor
      is overexpressed in Imerslund-Grasbeck syndrome.

PMID- 9649474
TI  - Treatment of fibrosing cholestatic hepatitis with lamivudine.
AB  - Fibrosing cholestatic hepatitis is a histological variant of hepatitis B virus
      infection with a high rate of mortality. We describe a patient who acquired acute
      hepatitis B virus infection 8 months after renal transplantation. Clinical
      features of rapidly progressive liver failure, indicated by prolonged prothrombin
      time (57 seconds) and increased bilirubin (40.4 mg/dL) and ammonia (129 mumol/L)
      concentrations, were accompanied by an extremely high serum HBV DNA level (2.153
      x 10(6) pg/mL). Liver biopsy specimen showed fibrosing cholestatic hepatitis with
      widespread balloon degeneration of hepatocytes, focal hepatocyte loss, bile
      stasis, periportal fibrosis, mild lymphocytic infiltration, and strongly positive
      immunohistochemical staining for hepatitis B surface antigen (HBsAg) and
      hepatitis B core antigen. Lamivudine therapy suppressed HBV DNA to < 10 pg/mL
      within 4 weeks, which was followed by gradual recovery of liver function from a
      state of hepatic precoma. Twenty-four months after the onset of hepatitis, the
      patient had normal prothrombin time and bilirubin, transaminase, and albumin
      levels. She remained HBsAg positive and hepatitis B e antigen negative. Renal
      allograft function was stable, with a creatinine level of 1.52 mg/dL. HBV DNA
      remained suppressed after 22 months of lamivudine therapy. Our experience shows
      that fibrosing cholestatic hepatitis and liver failure caused by HBV infection
      can be successfully treated with lamivudine.

PMID- 9649475
TI  - Inflammatory bowel disease: etiology and pathogenesis.

PMID- 9649476
TI  - The pathogenesis of celiac disease.

PMID- 9649477
TI  - Diagnosis of celiac sprue.

PMID- 9649478
TI  - Gastroenterology and hepatology look to the future.

PMID- 9649479
TI  - Intestinal graft-versus-host disease.

PMID- 9649480
TI  - The acid suppression test for unexplained chest pain.

PMID- 9649481
TI  - PKC isoforms: villains in colon cancer?

PMID- 9649482
TI  - Selective COX-2 inhibitors: are they safe for the stomach?

PMID- 9649483
TI  - Blocking the bleeding way.

PMID- 9649484
TI  - Enteropathogenic E. coli: intimacy redefined.

PMID- 9649485
TI  - Less than an ounce of prevention.

PMID- 9649486
TI  - Association of primary sclerosing cholangitis and colorectal cancer in patients
      with ulcerative colitis: is it true and does it matter?

PMID- 9649488
TI  - Unintentional Gluten Ingestion in Celiac Patients.

PMID- 9649487
TI  - Pancreatoduodenectomy for chronic pancreatitis.

PMID- 9649489
TI  - Insensitivity of the CLOtest for H. pylori, Especially in the Elderly.

PMID- 9649491
TI  - The Relevance of Luminal Release Is Doubtful.

PMID- 9649490
TI  - HCV NS5A mutations in Europeans infected by genotype 1b.

PMID- 9649492
TI  - Histamine H3 Receptors and Gastric Acid Secretion.

PMID- 9649493
TI  - Benefits of colorectal cancer patient follow-up.

PMID- 9649494
TI  - Surveillance after colorectal cancer: the final word?

PMID- 9649495
TI  - Follow-up after curative resection for colorectal cancer.

PMID- 9649496
TI  - Image of the Month Answer.

PMID- 9649497
TI  - Groucho proteins: transcriptional corepressors for specific subsets of DNA
      binding transcription factors in vertebrates and invertebrates.

PMID- 9649498
TI  - Inhibition of the anti-apoptotic PI(3)K/Akt/Bad pathway by stress.
AB  - The initiation of apoptosis often transpires in the presence of agents that
      regulate cell survival. This study evaluated the effects of stress-induced
      ceramide on the anti-apoptotic activity of the phosphoinositide-3 kinase [PI(3)K]
      pathway. PI(3)K activity is directly down-regulated by stress-induced ceramide in
      a dose-dependent manner with rapid kinetics and high specificity. Ceramide
      inhibition of PI(3)K is dependent on acid-sphingomyelinase. Down-regulation of
      PI(3)K by ceramide results in inhibition of the kinase Akt and decreased
      phosphorylation of the death effector Bad. Thus, ceramide levels could act as a
      general apoptotic rheostat controlling cell survival by regulating PI(3)K anti
      apoptotic effector mechanisms.

PMID- 9649499
TI  - pha-4, an HNF-3 homolog, specifies pharyngeal organ identity in Caenorhabditis
      elegans.
AB  - To build complex organs, embryos have evolved mechanisms that integrate the
      development of cells unrelated to one another by cell type or ancestry. Here we
      show that the pha-4 locus establishes organ identity for the Caenorhabditis
      elegans pharynx. In pha-4 mutants, pharyngeal cells are transformed into
      ectoderm. Conversely, ectopic pha-4 expression produces excess pharyngeal cells.
      pha-4 encodes an HNF-3 homolog selectively expressed in the nascent digestive
      tract, including all pharynx precursors at the time they are restricted to a
      pharyngeal fate. We suggest that pha-4 is a key component of a transcription
      based mechanism to endow cells with pharyngeal organ identity.

PMID- 9649500
TI  - Antigen receptor signaling induces MAP kinase-mediated phosphorylation and
      degradation of the BCL-6 transcription factor.
AB  - The bcl-6 proto-oncogene encodes a POZ/zinc finger transcriptional repressor
      expressed in germinal center (GC) B and T cells and required for GC formation and
      antibody affinity maturation. Deregulation of bcl-6 expression by chromosomal
      rearrangements and point mutations of the bcl-6 promoter region are implicated in
      the pathogenesis of B-cell lymphoma. The signals regulating bcl-6 expression are
      not known. Here we show that antigen receptor activation leads to BCL-6
      phosphorylation by mitogen-activated protein kinase (MAPK). Phosphorylation, in
      turn, targets BCL-6 for rapid degradation by the ubiquitin/proteasome pathway.
      These findings indicate that BCL-6 expression is directly controlled by the
      antigen receptor via MAPK activation. This signaling pathway may be crucial for
      the control of B-cell differentiation and antibody response and has implications
      for the regulation of other POZ/zinc finger transcription factors in other
      tissues.

PMID- 9649501
TI  - Negative regulation of the heat shock transcriptional response by HSBP1.
AB  - In response to stress, heat shock factor 1 (HSF1) acquires rapid DNA binding and
      transient transcriptional activity while undergoing conformational transition
      from an inert non-DNA-binding monomer to active functional trimers. Attenuation
      of the inducible transcriptional response occurs during heat shock or upon
      recovery at non-stress conditions and involves dissociation of the HSF1 trimer
      and loss of activity. We have used the hydrophobic repeats of the HSF1
      trimerization domain in the yeast two-hybrid protein interaction assay to
      identify heat shock factor binding protein 1 (HSBP1), a novel, conserved, 76
      amino-acid protein that contains two extended arrays of hydrophobic repeats that
      interact with the HSF1 heptad repeats. HSBP1 is nuclear-localized and interacts
      in vivo with the active trimeric state of HSF1 that appears during heat shock.
      During attenuation of HSF1 to the inert monomer, HSBP1 associates with Hsp70.
      HSBP1 negatively affects HSF1 DNA-binding activity, and overexpression of HSBP1
      in mammalian cells represses the transactivation activity of HSF1. To establish a
      biological role for HSBP1, the homologous Caenorhabditis elegans protein was
      overexpressed in body wall muscle cells and was shown to block activation of the
      heat shock response from a heat shock promoter-reporter construct. Alteration in
      the level of HSBP1 expression in C. elegans has severe effects on survival of the
      animals after thermal and chemical stress, consistent with a role for HSBP1 as a
      negative regulator of the heat shock response.

PMID- 9649502
TI  - Suppression of the p300-dependent mdm2 negative-feedback loop induces the p53
      apoptotic function.
AB  - The p53 tumor suppressor gene product interacts with the p300 transcriptional
      coactivator that regulates the transactivation of p53-inducible genes. The
      adenovirus E1A protein has been shown to bind to p300 and inhibit its function.
      E1A inhibits p53 transactivation and also promotes p53 accumulation by a p300
      dependent mechanism. Murine double minute 2 (Mdm2) is a transcriptional target of
      p53 that binds to p53 and inhibits its transcriptional activity. E1A inhibited
      mdm2 transactivation without affecting the expression of p21(WAF1) or Bax, which
      resulted in high levels of p53 accumulation and apoptosis. Ectopic expression of
      p300 restored Mdm2 levels and inhibited p53-dependent apoptosis, as did ectopic
      expression of Mdm2. Thus, p300 is required for mdm2 induction by p53 and the
      subsequent inhibition of p53 stabilization. Inhibition of p300 by E1A results in
      stabilization of p53 and causes apoptosis. Moreover, E1B 19K or Bcl-2 expression
      in E1A-transformed cells abrogated p53-dependent apoptosis by restoring mdm2
      transactivation by p53. Hence, p300 regulation of mdm2 expression controls
      apoptotic activity of p53, and 19K or Bcl-2 bypass E1A inhibition of p300
      transactivation of Mdm2.

PMID- 9649503
TI  - Identification of Xenopus SMC protein complexes required for sister chromatid
      cohesion.
AB  - The structural maintenance of chromosomes (SMC) family is a growing family of
      chromosomal ATPases. The founding class of SMC protein complexes, condensins,
      plays a central role in mitotic chromosome condensation. We report here a new
      class of SMC protein complexes containing XSMC1 and XSMC3, Xenopus homologs of
      yeast Smc1p and Smc3p, respectively. The protein complexes (termed cohesins)
      exist as two major forms with sedimentation coefficients of 9S and 14S. 9S
      cohesin is a heterodimer of XSMC1 and XSMC3, whereas 14S cohesin contains three
      additional subunits. One of them has been identified as a Xenopus homolog of the
      Schizosaccharomyces pombe Rad21p implicated in DNA repair and the Saccharomyces
      cerevisiae Scc1p/Mcd1p implicated in sister chromatid cohesion. 14S cohesin binds
      to interphase chromatin independently of DNA replication and dissociates from it
      at the onset of mitosis. Immunodepletion of cohesins during interphase causes
      defects in sister chromatid cohesion in subsequent mitosis, whereas condensation
      is unaffected. These results suggest that proper assembly of mitotic chromosomes
      is regulated by two distinct classes of SMC protein complexes, cohesins and
      condensins.

PMID- 9649504
TI  - Identification of functional exonic splicing enhancer motifs recognized by
      individual SR proteins.
AB  - Using an in vitro randomization and functional selection procedure, we have
      identified three novel classes of exonic splicing enhancers (ESEs) recognized by
      human SF2/ASF, SRp40, and SRp55, respectively. These ESEs are functional in
      splicing and are highly specific. For SF2/ASF and SRp55, in most cases, only the
      cognate SR protein can efficiently recognize an ESE and activate splicing. In
      contrast, the SRp40-selected ESEs can function with either SRp40 or SRp55, but
      not with SF2/ASF. UV cross-linking/competition and immunoprecipitation
      experiments showed that SR proteins recognize their cognate ESEs in nuclear
      extract by direct and specific binding. A motif search algorithm was used to
      derive consensus sequences for ESEs recognized by these SR proteins. Each SR
      protein yielded a distinct 5- to 7-nucleotide degenerate consensus. These three
      consensus sequences occur at higher frequencies in exons than in introns and may
      thus help define exon-intron boundaries. They occur in clusters within regions
      corresponding to naturally occurring, mapped ESEs. We conclude that a remarkably
      diverse set of sequences can function as ESEs. The degeneracy of these motifs is
      consistent with the fact that exonic enhancers evolved within extremely diverse
      protein coding sequences and are recognized by a small number of SR proteins that
      bind RNA with limited sequence specificity.

PMID- 9649505
TI  - The ROOT HAIRLESS 1 gene encodes a nuclear protein required for root hair
      initiation in Arabidopsis.
AB  - The epidermis of Arabidopsis wild-type primary roots, in which some cells grow
      hairs and others remain hairless in a position-dependent manner, has become an
      established model system to study cell differentiation. Here we present a
      molecular analysis of the RHL1 (ROOT HAIRLESS 1) gene that, if mutated, prevents
      the formation of hairs on primary roots and causes a seedling lethal phenotype.
      We have cloned the RHL1 gene by use of a T-DNA-tagged mutant and found that it
      encodes a protein that appears to be plant specific. The predicted RHL1 gene
      product is a small hydrophilic protein (38.9 kD) containing putative nuclear
      localization signals and shows no significant homology to any known amino acid
      sequence. We demonstrate that a 78-amino-acid sequence at its amino terminus is
      capable of directing an RHL1-GFP fusion protein to the nucleus. The RHL1
      transcript is present throughout the wild-type plant and in suspension culture
      cells, but in very low amounts, suggesting a regulatory function for the RHL1
      protein. Structural evidence suggests a role for the RHL1 gene product in the
      nucleolus. We have examined the genetic relationship between RHL1 and GL2, an
      inhibitor of root hair initiation in non-hair cells. Our molecular and genetic
      data with double mutants, together with the expression analysis of a GL2 promoter
      GUS reporter gene construct, indicate that the RHL1 gene acts independently of
      GL2.

PMID- 9649506
TI  - Functional intertwining of Dpp and EGFR signaling during Drosophila endoderm
      induction.
AB  - Endoderm induction in Drosophila is mediated by the extracellular signals
      Decapentaplegic (Dpp) and Wingless (Wg). We discovered a secondary signal with a
      permissive role in this process, namely Vein, a neuregulin-like ligand that
      stimulates the epidermal growth factor receptor (EGFR) and Ras signaling. Dpp and
      Wg up-regulate vein expression in the midgut mesoderm in two regions overlapping
      the Dpp sources. Experiments based on lack of function and ectopic stimulation of
      Dpp and EGFR signaling show that these two pathways are functionally
      interdependent and that they synergize with each other, revealing functional
      intertwining. The transcriptional response elements for the Dpp signal in midgut
      enhancers from homeotic target genes are bipartite, comprising CRE sites as well
      as binding sites for the Dpp signal-transducing protein Mad. Of these sites, the
      CRE seems to function primarily in the response to Ras, the secondary signal of
      Dpp. We discuss the potential significance of why an inductive process might use
      a secondary signal whose function is intertwined with that of the primary signal.

PMID- 9649507
TI  - Proneural gene self-stimulation in neural precursors: an essential mechanism for
      sense organ development that is regulated by Notch signaling.
AB  - To learn about the acquisition of neural fate by ectodermal cells, we have
      analyzed a very early sign of neural commitment in Drosophila, namely the
      specific accumulation of achaete-scute complex (AS-C) proneural proteins in the
      cell that becomes a sensory organ mother cell (SMC). We have characterized an AS
      C enhancer that directs expression specifically in SMCs. This enhancer promotes
      Scute protein accumulation in these cells, an event essential for sensory organ
      development in the absence of other AS-C genes. Interspecific sequence
      comparisons and site-directed mutagenesis show the presence of several conserved
      motifs necessary for enhancer action, some of them binding sites for proneural
      proteins. These and other data indicate that the enhancer mediates scute self
      stimulation, although only in the presence of additional activating factors,
      which most likely interact with conserved motifs reminiscent of NF-kappaB-binding
      sites. Cells neighboring the SMC do not acquire the neural fate because the Notch
      signaling pathway effectors, the Enhancer of split bHLH proteins, block this
      proneural gene self-stimulatory loop, possibly by antagonizing the action on the
      enhancer of the NF-kappaB-like factors or the proneural proteins. These data
      suggest a mechanism for SMC committment.

PMID- 9649508
TI  - Self-renewal of pluripotent embryonic stem cells is mediated via activation of
      STAT3.
AB  - The propagation of embryonic stem (ES) cells in an undifferentiated pluripotent
      state is dependent on leukemia inhibitory factor (LIF) or related cytokines.
      These factors act through receptor complexes containing the signal transducer
      gp130. The downstream mechanisms that lead to ES cell self-renewal have not been
      delineated, however. In this study, chimeric receptors were introduced into ES
      cells. Biochemical and functional studies of transfected cells demonstrated a
      requirement for engagement and activation of the latent trancription factor
      STAT3. Detailed mutational analyses unexpectedly revealed that the four STAT3
      docking sites in gp130 are not functionally equivalent. The role of STAT3 was
      then investigated using the dominant interfering mutant, STAT3F. ES cells that
      expressed this molecule constitutively could not be isolated. An episomal
      supertransfection strategy was therefore used to enable the consequences of
      STAT3F expression to be examined. In addition, an inducible STAT3F transgene was
      generated. In both cases, expression of STAT3F in ES cells growing in the
      presence of LIF specifically abrogated self-renewal and promoted differentiation.
      These complementary approaches establish that STAT3 plays a central role in the
      maintenance of the pluripotential stem cell phenotype. This contrasts with the
      involvement of STAT3 in the induction of differentiation in somatic cell types.
      Cell type-specific interpretation of STAT3 activation thus appears to be pivotal
      to the diverse developmental effects of the LIF family of cytokines.
      Identification of STAT3 as a key transcriptional determinant of ES cell self
      renewal represents a first step in the molecular characterization of
      pluripotency.

PMID- 9649509
TI  - Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3
      and inhibits its transcriptional activity.
AB  - Interferon regulatory factor-3 (IRF-3) was found to specifically interact with
      HPV16 E6 in a yeast two-hybrid screen. IRF-3 is activated by the presence of
      double-stranded RNA or by virus infection to form a stable complex with other
      transcriptional regulators that bind to the regulatory elements of the IFNbeta
      promoter. We show that IRF-3 is a potent transcriptional activator and
      demonstrate that HPV16 E6 can inhibit its transactivation function. The
      expression of HPV16 E6 in primary human keratinocytes inhibits the induction of
      IFNbeta mRNA following Sendai virus infection. The binding of HPV16 E6 to IRF-3
      does not result in its ubiquitination or degradation. We propose that the
      interaction of E6 with IRF-3 and the inhibition of IRF-3's transcriptional
      activity may provide the virus a means to circumvent the normal antiviral
      response of an HPV16-infected cell.

PMID- 9649510
TI  - New POU dimer configuration mediates antagonistic control of an osteopontin
      preimplantation enhancer by Oct-4 and Sox-2.
AB  - The POU transcription factor Oct-4 is expressed specifically in the germ line,
      pluripotent cells of the pregastrulation embryo and stem cell lines derived from
      the early embryo. Osteopontin (OPN) is a protein secreted by cells of the
      preimplantation embryo and contains a GRGDS motif that can bind to specific
      integrin subtypes and modulate cell adhesion/migration. We show that Oct-4 and
      OPN are coexpressed in the preimplantation mouse embryo and during
      differentiation of embryonal cell lines. Immunoprecipitation of the first intron
      of OPN (i-opn) from covalently fixed chromatin of embryonal stem cells by Oct-4
      specific antibodies indicates that Oct-4 binds to this fragment in vivo. The i
      opn fragment functions as an enhancer in cell lines that resemble cells of the
      preimplantation embryo. Furthermore, it contains a novel palindromic Oct factor
      recognition element (PORE) that is composed of an inverted pair of homeodomain
      binding sites separated by exactly 5 bp (ATTTG +5 CAAAT). POU proteins can homo-
      and heterodimerize on the PORE in a configuration that has not been described
      previously. Strong transcriptional activation of the OPN element requires an
      intact PORE. In contrast, the canonical octamer overlapping with the downstream
      half of the PORE is not essential. Sox-2 is a transcription factor that contains
      an HMG box and is coexpressed with Oct-4 in the early mouse embryo. Sox-2
      represses Oct-4 mediated activation of i-opn by way of a canonical Sox element
      that is located close to the PORE. Repression depends on a carboxy-terminal
      region of Sox-2 that is outside of the HMG box. Expression, DNA binding, and
      transactivation data are consistent with the hypothesis that OPN expression is
      regulated by Oct-4 and Sox-2 in preimplantation development.

PMID- 9649511
TI  - The language of gene interaction.

PMID- 9649512
TI  - UV light induces IS10 transposition in Escherichia coli.
AB  - A new mutagenesis assay system based on the phage 434 cI gene carried on a low
      copy number plasmid was used to investigate the effect of UV light on
      intermolecular transposition of IS10. Inactivation of the target gene by IS10
      insertion was detected by the expression of the tet gene from the phage 434 PR
      promoter, followed by Southern blot analysis of plasmids isolated from TetR
      colonies. UV irradiation of cells harboring the target plasmid and a donor
      plasmid carrying an IS10 element led to an increase of up to 28-fold in IS10
      transposition. Each UV-induced transposition of IS10 was accompanied by fusion of
      the donor and acceptor plasmid into a cointegrate structure, due to coupled
      homologous recombination at the insertion site, similar to the situation in
      spontaneous IS10 transposition. UV radiation also induced transposition of IS10
      from the chromosome to the target plasmid, leading almost exclusively to the
      integration of the target plasmid into the chromosome. UV induction of IS10
      transposition did not depend on the umuC and uvrA gene product, but it was not
      observed in lexA3 and DeltarecA strains, indicating that the SOS stress response
      is involved in regulating UV-induced transposition. IS10 transposition, known to
      increase the fitness of Escherichia coli, may have been recruited under the SOS
      response to assist in increasing cell survival under hostile environmental
      conditions. To our knowledge, this is the first report on the induction of
      transposition by a DNA-damaging agent and the SOS stress response in bacteria.

PMID- 9649513
TI  - Salmonella virulence plasmid. Modular acquisition of the spv virulence region by
      an F-plasmid in Salmonella enterica subspecies I and insertion into the
      chromosome of subspecies II, IIIa, IV and VII isolates.
AB  - The spv operon is common to all Salmonella virulence plasmids. DNA hybridization
      analysis indicates that the spv region is limited in distribution to serovars of
      Salmonella enterica subspecies I, II, IIIa, IV, and VII and is absent from
      Salmonella bongori isolates. Among strains of subspecies II, IIIa, and VII, all
      isolates examined contained sequences that hybridized with the spv region.
      However, among isolates of subspecies I, DNA sequences capable of hybridizing
      with the spv region were found in some isolates of certain serovars. Furthermore,
      in isolates of subspecies I, the virulence plasmid was found in the same set of
      isolates as an F-related plasmid, as determined by the presence of the spv region
      of the virulence plasmid and the finO, traD, and repA sequences of the F-plasmid.
      The concordance of the virulence plasmid and all three F-plasmid sequences in
      subspecies I serovar Choleraesuis, Paratyphi, and Typhimurium is most easily
      explained if the spv region is carried in an F-related plasmid in these isolates.
      In contrast, among S. enterica subspecies II, IIIa, IV, and VII, the isolates
      that contain spv sequences did not hybridize with an F-related plasmid or any
      other identifiable plasmid. With the use of pulse-field gel electrophoresis, the
      spv region in subspecies II, IIIa, and VII was found to be encoded on the
      chromosome. Analysis of the phylogenetic distribution of spv among Salmonella
      isolates and comparative nucleotide sequence analysis of spvA and spvC suggests
      that the spv region was acquired very recently, after speciation of the
      salmonellae.

PMID- 9649514
TI  - The M26 hotspot of Schizosaccharomyces pombe stimulates meiotic ectopic
      recombination and chromosomal rearrangements.
AB  - Homologous recombination is increased during meiosis between DNA sequences at the
      same chromosomal position (allelic recombination) and at different chromosomal
      positions (ectopic recombination). Recombination hotspots are important elements
      in controlling meiotic allelic recombination. We have used artificially dispersed
      copies of the ade6 gene in Schizosaccharomyces pombe to study hotspot activity in
      meiotic ectopic recombination. Ectopic recombination was reduced 10-1000-fold
      relative to allelic recombination, and was similar to the low frequency of
      ectopic recombination between naturally repeated sequences in S. pombe. The M26
      hotspot was active in ectopic recombination in some, but not all, integration
      sites, with the same pattern of activity and inactivity in ectopic and allelic
      recombination. Crossing over in ectopic recombination, resulting in chromosomal
      rearrangements, was associated with 35-60% of recombination events and was
      stimulated 12-fold by M26. These results suggest overlap in the mechanisms of
      ectopic and allelic recombination and indicate that hotspots can stimulate
      chromosomal rearrangements.

PMID- 9649515
TI  - Distribution of a limited Sir2 protein pool regulates the strength of yeast rDNA
      silencing and is modulated by Sir4p.
AB  - Transcriptional silencing in Saccharomyces cerevisiae occurs at the silent mating
      type loci HML and HMR, at telomeres, and at the ribosomal DNA (rDNA) locus RDN1.
      Silencing in the rDNA occurs by a novel mechanism that depends on a single Silent
      Information Regulator (SIR) gene, SIR2. SIR4, essential for other silenced loci,
      paradoxically inhibits rDNA silencing. In this study, we elucidate a regulatory
      mechanism for rDNA silencing based on the finding that rDNA silencing strength
      directly correlates with cellular Sir2 protein levels. The endogenous level of
      Sir2p was shown to be limiting for rDNA silencing. Furthermore, small changes in
      Sir2p levels altered rDNA silencing strength. In rDNA silencing phenotypes, sir2
      mutations were shown to be epistatic to sir4 mutations, indicating that SIR4
      inhibition of rDNA silencing is mediated through SIR2. Furthermore, rDNA
      silencing is insensitive to SIR3 overexpression, but is severely reduced by
      overexpression of full-length Sir4p or a fragment of Sir4p that interacts with
      Sir2p. This negative effect of SIR4 overexpression was overridden by co
      overexpression of SIR2, suggesting that SIR4 directly inhibits the rDNA silencing
      function of SIR2. Finally, genetic manipulations of SIR4 previously shown to
      promote extended life span also resulted in enhanced rDNA silencing. We propose a
      simple model in which telomeres act as regulators of rDNA silencing by competing
      for limiting amounts of Sir2 protein.

PMID- 9649516
TI  - Fission yeast cdc24(+) encodes a novel replication factor required for chromosome
      integrity.
AB  - A mutation within the Schizosaccharomyces pombe cdc24(+) gene was identified
      previously in a screen for cell division cycle mutants and the cdc24(+) gene was
      determined to be essential for S phase in this yeast. We have isolated the
      cdc24(+) gene by complementation of a new temperature-sensitive allele of the
      gene, cdc24-G1. The DNA sequence predicts the presence of an open reading frame
      punctuated by six introns which encodes a pioneer protein of 58 kD. A cdc24 null
      mutant was generated by homologous recombination. Haploid cells lacking cdc24(+)
      are inviable, indicating that cdc24(+) is an essential gene. The transcript of
      cdc24(+) is present at constant levels throughout the cell cycle. Cells lacking
      cdc24(+) function show a checkpoint-dependent arrest with a 2N DNA content,
      indicating a block late in S phase. Arrest is accompanied by a rapid loss of
      viability and chromosome breakage. An S. pombe homolog of the replicative DNA
      helicase DNA2 of S. cerevisiae suppresses cdc24. These results suggest that
      Cdc24p plays a role in the progression of normal DNA replication and is required
      to maintain genomic integrity.

PMID- 9649517
TI  - Effects of DNA double-strand and single-strand breaks on intrachromosomal
      recombination events in cell-cycle-arrested yeast cells.
AB  - Intrachromosomal recombination between repeated elements can result in deletion
      (DEL recombination) events. We investigated the inducibility of such
      intrachromosomal recombination events at different stages of the cell cycle and
      the nature of the primary DNA lesions capable of initiating these events. Two
      genetic systems were constructed in Saccharomyces cerevisiae that select for DEL
      recombination events between duplicated alleles of CDC28 and TUB2. We determined
      effects of double-strand breaks (DSBs) and single-strand breaks (SSBs) between
      the duplicated alleles on DEL recombination when induced in dividing cells or
      cells arrested in G1 or G2. Site-specific DSBs and SSBs were produced by
      overexpression of the I-Sce I endonuclease and the gene II protein (gIIp),
      respectively. I-Sce I-induced DSBs caused an increase in DEL recombination
      frequencies in both dividing and cell-cycle-arrested cells, indicating that G1-
      and G2-arrested cells are capable of completing DSB repair. In contrast, gIIp
      induced SSBs caused an increase in DEL recombination frequency only in dividing
      cells. To further examine these phenomena we used both gamma-irradiation,
      inducing DSBs as its most relevant lesion, and UV, inducing other forms of DNA
      damage. UV irradiation did not increase DEL recombination frequencies in G1 or
      G2, whereas gamma-rays increased DEL recombination frequencies in both phases.
      Both forms of radiation, however, induced DEL recombination in dividing cells.
      The results suggest that DSBs but not SSBs induce DEL recombination, probably via
      the single-strand annealing pathway. Further, DSBs in dividing cells may result
      from the replication of a UV or SSB-damaged template. Alternatively, UV induced
      events may occur by replication slippage after DNA polymerase pausing in front of
      the damage.

PMID- 9649518
TI  - A screen for genes involved in the anaphase proteolytic pathway identifies
      tsm1(+), a novel Schizosaccharomyces pombe gene important for microtubule
      integrity.
AB  - The growth of several mitotic mutants of Schizosaccharomyces pombe, including
      nuc2-663, is inhibited by the protease inhibitor N-Tosyl-L-Phenylalanine
      Chloromethyl Ketone (TPCK). Because nuc2(+) encodes a presumptive component of
      the Anaphase Promoting Complex, which is required for the ubiquitin-dependent
      proteolysis of certain proteins during exit from mitosis, we have used
      sensitivity to TPCK as a criterion by which to search for novel S. pombe mutants
      defective in the anaphase-promoting pathway. In a genetic screen for temperature
      sensitive mitotic mutants that were also sensitive to TPCK at a permissive
      temperature, we isolated three tsm (TPCK-sensitive mitotic) strains. Two of these
      are alleles of cut1(+), but tsm1-512 maps to a novel genetic location. The tsm1
      512 mutation leads to delayed nuclear division at restrictive temperatures,
      apparently as a result of an impaired ability to form a metaphase spindle. After
      shift of early G2 cells to 36 degrees, tsm1-512 arrests transiently in the second
      mitotic division and then exits mitosis, as judged by spindle elongation and
      septation. The chromosomes, however, often fail to segregate properly. Genetic
      interactions between tsm1-512 and components of the anaphase proteolytic pathway
      suggest a functional involvement of the Tsm1 protein in this pathway.

PMID- 9649519
TI  - Isolation and characterization of new fission yeast cytokinesis mutants.
AB  - Schizosaccharomyces pombe is an excellent organism in which to study cytokinesis
      as it divides by medial fission using an F-actin contractile ring. To enhance our
      understanding of the cell division process, a large genetic screen was carried
      out in which 17 genetic loci essential for cytokinesis were identified, 5 of
      which are novel. Mutants identifying three genes, rng3(+), rng4(+), and rng5(+),
      were defective in organizing an actin contractile ring. Four mutants defective in
      septum deposition, septum initiation defective (sid)1, sid2, sid3, and sid4, were
      also identified and characterized. Genetic analyses revealed that the sid mutants
      display strong negative interactions with the previously described septation
      mutants cdc7-24, cdc11-123, and cdc14-118. The rng5(+), sid2(+), and sid3(+)
      genes were cloned and shown to encode Myo2p (a myosin heavy chain), a protein
      kinase related to budding yeast Dbf2p, and Spg1p, a GTP binding protein that is a
      member of the ras superfamily of GTPases, respectively. The ability of Spg1p to
      promote septum formation from any point in the cell cycle depends on the activity
      of Sid4p. In addition, we have characterized a phenotype that has not been
      described previously in cytokinesis mutants, namely the failure to reorganize
      actin patches to the medial region of the cell in preparation for septum
      formation.

PMID- 9649520
TI  - The PBN1 gene of Saccharomyces cerevisiae: an essential gene that is required for
      the post-translational processing of the protease B precursor.
AB  - The vacuolar hydrolase protease B in Saccharomyces cerevisiae is synthesized as
      an inactive precursor (Prb1p). The precursor undergoes post-translational
      modifications while transiting the secretory pathway. In addition to N- and O
      linked glycosylations, four proteolytic cleavages occur during the maturation of
      Prb1p. Removal of the signal peptide by signal peptidase and the autocatalytic
      cleavage of the large amino-terminal propeptide occur in the endoplasmic
      reticulum (ER). Two carboxy-terminal cleavages of the post regions occur in the
      vacuole: the first cleavage is catalyzed by protease A and the second results
      from autocatalysis. We have isolated a mutant, pbn1-1, that exhibits a defect in
      the ER processing of Prb1p. The autocatalytic cleavage of the propeptide from
      Prb1p does not occur and Prb1p is rapidly degraded in the cytosol. PBN1 was
      cloned and is identical to YCL052c on chromosome III. PBN1 is an essential gene
      that encodes a novel protein. Pbn1p is predicted to contain a sub-C-terminal
      transmembrane domain but no signal sequence. A functional HA epitope-tagged Pbn1p
      fusion localizes to the ER. Pbn1p is N-glycosylated in its amino-terminal domain,
      indicating a lumenal orientation despite the lack of a signal sequence. Based on
      these results, we propose that one of the functions of Pbn1p is to aid in the
      autocatalytic processing of Prb1p.

PMID- 9649521
TI  - Tip loci: six Chlamydomonas nuclear suppressors that permit the translocation of
      proteins with mutant thylakoid signal sequences.
AB  - Mutations within the signal sequence of cytochrome f (cytf) in Chlamydomonas
      inhibit thylakoid membrane protein translocation and render cells
      nonphotosynthetic. Twenty-seven suppressors of the mutant signal sequences were
      selected for their ability to restore photoautotrophic growth and these describe
      six nuclear loci named tip1 through 6 for thylakoid insertion protein. The tip
      mutations restore the translocation of cytf and are not allele specific, as they
      suppress a number of different cytf signal sequence mutations. Tip5 and 2 may act
      early in cytf translocation, while Tip1, 3, 4, and 6 are engaged later. The tip
      mutations have no phenotype in the absence of a signal sequence mutation and
      there is genetic interaction between tip4, and tip5 suggesting an interaction of
      their encoded proteins. As there is overlap in the energetic, biochemical and
      genetic requirements for the translocation of nuclear and chloroplast-encoded
      thylakoid proteins, the tip mutations likely identify components of a general
      thylakoid protein translocation apparatus.

PMID- 9649522
TI  - A genetic screen for temperature-sensitive cell-division mutants of
      Caenorhabditis elegans.
AB  - A novel screen to isolate conditional cell-division mutants in Caenorhabditis
      elegans has been developed. The screen is based on the phenotypes associated with
      existing cell-division mutations: some disrupt postembryonic divisions and affect
      formation of the gonad and ventral nerve cord-resulting in sterile, uncoordinated
      animals-while others affect embryonic divisions and result in lethality. We
      obtained 19 conditional mutants that displayed these phenotypes when shifted to
      the restrictive temperature at the appropriate developmental stage. Eighteen of
      these mutations have been mapped; 17 proved to be single alleles of newly
      identified genes, while 1 proved to be an allele of a previously identified gene.
      Genetic tests on the embryonic lethal phenotypes indicated that for 13 genes,
      embryogenesis required maternal expression, while for 6, zygotic expression could
      suffice. In all cases, maternal expression of wild-type activity was found to be
      largely sufficient for embryogenesis. Cytological analysis revealed that 10
      mutants possessed embryonic cell-division defects, including failure to properly
      segregate DNA, failure to assemble a mitotic spindle, late cytokinesis defects,
      prolonged cell cycles, and improperly oriented mitotic spindles. We conclude that
      this approach can be used to identify mutations that affect various aspects of
      the cell-division cycle.

PMID- 9649523
TI  - A new marker for mosaic analysis in Caenorhabditis elegans indicates a fusion
      between hyp6 and hyp7, two major components of the hypodermis.
AB  - A fusion of the sur-5 protein to the green fluorescent protein containing a
      nuclear localization signal is demonstrated as a marker for genetic mosaic
      analysis in the nematode Caenorhabditis elegans. Because of an extensive
      accumulation of bright fluorescence in many nuclei, normal growth plates, each
      containing hundreds of worms, can be rapidly screened with a dissecting
      microscope for rare mosaic individuals. As the marker can also be used to detect
      transgenic worms, the construction of strains for mosaic analyses can be
      minimized. In the course of examining rare mosaic animals, an unexpected pattern
      of fluorescence was noticed for hyp6, a syncytial component of the hypodermis,
      which indicated that the marker may serve as a means of assessing cellular
      fusions during development. Immunofluorescent staining of adherens junctions
      confirmed a postembryonic fusion of hyp6 with hyp7, the major syncytium of the
      hypodermis.

PMID- 9649524
TI  - Identification of heterochronic mutants in Caenorhabditis elegans. Temporal
      misexpression of a collagen::green fluorescent protein fusion gene.
AB  - The heterochronic genes lin-4, lin-14, lin-28, and lin-29 specify the timing of
      lateral hypodermal seam cell terminal differentiation in Caenorhabditis elegans.
      We devised a screen to identify additional genes involved in this developmental
      timing mechanism based on identification of mutants that exhibit temporal
      misexpression from the col-19 promoter, a downstream target of the heterochronic
      gene pathway. We fused the col-19 promoter to the green fluorescent protein gene
      (gfp) and demonstrated that hypodermal expression of the fusion gene is adult
      specific in wild-type animals and temporally regulated by the heterochronic gene
      pathway. We generated a transgenic strain in which the col-19::gfp fusion
      construct is not expressed because of mutation of lin-4, which prevents seam cell
      terminal differentiation. We have identified and characterized 26 mutations that
      restore col-19::gfp expression in the lin-4 mutant background. Most of the
      mutations also restore other aspects of the seam cell terminal differentiation
      program that are defective in lin-4 mutant animals. Twelve mutations are alleles
      of three previously identified genes known to be required for proper timing of
      hypodermal terminal differentiation. Among these are four new alleles of lin-42,
      a heterochronic gene for which a single allele had been described previously. Two
      mutations define a new gene, lin-58. When separated from lin-4, the lin-58
      mutations cause precocious seam cell terminal differentiation and thus define a
      new member of the heterochronic gene pathway.

PMID- 9649525
TI  - Molecular evolution of a sex determination protein. FEM-2 (pp2c) in
      Caenorhabditis.
AB  - Somatic sex determination in Caenorhabditis elegans involves a signal
      transduction pathway linking a membrane receptor to a transcription factor. The
      fem-2 gene is central to this pathway, producing a protein phosphatase (FEM-2) of
      the type 2C (PP2C). FEM-2 contains a long amino terminus that is absent in
      canonical PP2C enzymes. The function of this domain is difficult to predict,
      since it shows no sequence similarity to any other known proteins or motifs. Here
      we report the cloning of the fem-2 homologue from Caenorhabditis briggsae (Cb-fem
      2). The sequence identity is much higher than that observed for other C. briggsae
      homologues of C. elegans sex determination proteins. However, this level is not
      uniform across the entire lengths of the proteins; it is much lower in the amino
      termini. Thus, the two domains of the same protein are evolving at different
      rates, suggesting that they have different functional constraints. Consistent
      with this, Cb-FEM-2 is able to replace some, but not all, of the Ce-FEM-2 in vivo
      function. We show that removal of the amino terminus from Ce-FEM-2 has no effect
      on its in vitro phosphatase activity, or its ability to replace the in vivo
      function of a yeast PP2C enzyme, but that it is necessary for proper FEM-2
      function in worms. This demonstrates that the amino terminus is not an extended
      catalytic domain or a direct negative regulator of phosphatase activity.

PMID- 9649526
TI  - The Y chromosomal fertility factor Threads in Drosophila hydei harbors a
      functional gene encoding an axonemal dynein beta heavy chain protein.
AB  - To understand the contradiction between megabase-sized lampbrush loops and
      putative protein encoding genes both associated with the loci of Y chromosomal
      fertility genes of Drosophila on the molecular level, we used PCR-mediated
      cloning to identify and isolate the cDNA sequence of the Y chromosomal Drosophila
      hydei gene DhDhc7(Y). Alignment of the sequences of the putative protein
      DhDhc7(Y) and the outer arm dynein beta heavy chain protein DYH2 of Tripneustes
      gratilla shows homology over the entire length of the protein chains. Therefore
      the proteins can be assumed to fulfill orthologous functions within the sperm
      tail axonemes of both species. Functional dynein beta heavy chain molecules,
      however, are necessary for the assembly and attachment of outer dynein arms
      within the sperm tail axoneme. Localization of DhDhc7(Y) to the fertility factor
      Threads, comprising at least 5.1 Mb of transcriptionally active repetitive DNA,
      results from an infertile Threads- mutant where large clusters of Threads
      specifically transcribed satellites and parts of DhDhc7(Y) encoding sequences are
      missing simultaneously. Consequently, the complete lack of the outer dynein arms
      in Threads- males most probably causes sperm immotility and hence infertility of
      the fly. Moreover, preliminary sequence analysis and several other features
      support the hypothesis that DhDhc7(Y) on the lampbrush loops Threads in D. hydei
      and Dhc-Yh3 on the lampbrush loops kl-5 in Drosophila melanogaster on the
      heterochromatic Y chromosome of both species might indeed code for orthologous
      dynein beta heavy chain proteins.

PMID- 9649527
TI  - Mitochondrial DNA haplotype frequencies in natural and experimental populations
      of Drosophila subobscura.
AB  - The evolution of Drosophila subobscura mitochondrial DNA has been studied in
      experimental populations, founded with flies from a natural population from
      Esporles (Majorca, Balearic Islands, Spain). This population, like other European
      ones, is characterized by the presence of two very common (>96%) mitochondrial
      haplotypes (called I and II) and rare and endemic haplotypes that appear at very
      low frequencies. There is no statistical evidence of positive Darwinian selection
      acting on the mitochondrial DNA variants according to Tajima's neutrality test.
      Two experimental populations, with one replicate each, were established with
      flies having a heterogeneous nuclear genetic background, which was representative
      of the composition of the natural population. Both populations were started with
      the two most frequent mitochondrial haplotypes, but at different initial
      frequencies. After 13 to 16 generations, haplotype II reached fixation in three
      cages and its frequency was 0.89 by generation 25 in the fourth cage. Random
      drift can be rejected as the force responsible for the observed changes in
      haplotype frequencies. There is not only statistical evidence of a linear trend
      favoring a mtDNA (haploid) fitness effect, but also of a significant nonlinear
      deviation that could be due to a nuclear component.

PMID- 9649528
TI  - Evaluating gene flow using selected markers: a case study.
AB  - The extent to which an organism is locally adapted in an environmental pocket
      depends on the selection intensities inside and outside the pocket, on migration,
      and on the size of the pocket. When two or more loci are involved in this local
      adaptation, measuring their frequency gradients and their linkage disequilbria
      allows one to disentangle the forces-migration and selection-acting on the
      system. We apply this method to the case of a local adaptation to organophosphate
      insecticides in the mosquito Culex pipiens pipiens in southern France. The study
      of two different resistance loci allowed us to estimate with support limits gene
      flow as well as selection pressure on insecticide resistance and the fitness
      costs associated with each locus. These estimates permit us to pinpoint the
      conditions for the maintenance of this pocket of adaptation as well as the effect
      of the interaction between the two resistance loci.

PMID- 9649529
TI  - hobo Induced rearrangements in the yellow locus influence the insulation effect
      of the gypsy su(Hw)-binding region in Drosophila melanogaster.
AB  - The su(Hw) protein is responsible for the insulation mediated by the su(Hw)
      binding region present in the gypsy retrotransposon. In the y2 mutant, su(Hw)
      protein partially inhibits yellow transcription by repressing the function of
      transcriptional enhancers located distally from the yellow promoter with respect
      to gypsy. y2 mutation derivatives have been induced by the insertion of two hobo
      copies on the both sides of gypsy: into the yellow intron and into the 5'
      regulatory region upstream of the wing and body enhancers. The hobo elements have
      the same structure and orientation, opposite to the direction of yellow
      transcription. In the sequence context, where two copies of hobo are separated by
      the su(Hw)-binding region, hobo-dependent rearrangements are frequently
      associated with duplications of the region between the hobo elements. Duplication
      of the su(Hw)-binding region strongly inhibits the insulation of the yellow
      promoter separated from the body and wing enhancers by gypsy. These results
      provide a better insight into mechanisms by which the su(Hw)-binding region
      affects the enhancer function.

PMID- 9649530
TI  - Courtship and visual defects of cacophony mutants reveal functional complexity of
      a calcium-channel alpha1 subunit in Drosophila.
AB  - We show by molecular analysis of behavioral and physiological mutants that the
      Drosophila Dmca1A calcium-channel alpha1 subunit is encoded by the cacophony
      (cac) gene and that nightblind-A and lethal(1)L13 mutations are allelic to cac
      with respect to an expanded array of behavioral and physiological phenotypes
      associated with this gene. The cacS mutant, which exhibits defects in the
      patterning of courtship lovesong and a newly revealed but subtle abnormality in
      visual physiology, is mutated such that a highly conserved phenylalanine (in one
      of the quasi-homologous intrapolypeptide regions called IIIS6) is replaced by
      isoleucine. The cacH18 mutant exhibits defects in visual physiology (including
      complete unresponsiveness to light in certain genetic combinations) and visually
      mediated behaviors; this mutant (originally nbAH18) has a stop codon in an
      alternative exon (within the cac ORF), which is differentially expressed in the
      eye. Analysis of the various courtship and visual phenotypes associated with this
      array of cac mutants demonstrates that Dmca1A calcium channels mediate multiple,
      separable biological functions; these correlate in part with transcript diversity
      generated via alternative splicing.

PMID- 9649531
TI  - Molecular screening for P-element insertions in a large genomic region of
      Drosophila melanogaster using polymerase chain reaction mediated by the
      vectorette.
AB  - As an alternative to existing methods for the detection of new insertions during
      a transposon mutagenesis, we adapted the method of vectorette ligation to genomic
      restriction fragments followed by PCR to obtain genomic sequences flanking the
      transposon. By combining flies containing a defined genomic transposon with an
      excess of flies containing unrelated insertion sites, we demonstrate the
      specificity and sensitivity of the procedure in the detection of integration
      events. This method was applied in a transposon-tagging screen for BJ1, the
      Drosophila homolog of the vertebrate gene Regulator of Chromosome Condensation
      (RCCI). Genetic mobilization of a single genomic P element was used to generate
      preferentially new local insertions from which integrations into a genomic region
      surrounding the BJ1 gene were screened. Flies harboring new insertions were
      phenotypically selected on the basis of the zeste1-dependent transvection of
      white. We detected a single transposition to a 13-kb region close to the BJ1 gene
      among 6650 progeny that were analyzed. Southern analysis of the homozygous line
      confirmed the integration 3 kb downstream of BJ1.

PMID- 9649532
TI  - Loss of notum macrochaetae as an interspecific hybrid anomaly between Drosophila
      melanogaster and D. simulans.
AB  - With the aim of revealing genetic variation accumulated among closely related
      species during the course of evolution, this study focuses on loss of
      macrochaetae on the notum as one of the developmental anomalies seen in
      interspecific hybrids between Drosophila melanogaster and its closely related
      species. Interspecific hybrids between a line of D. melanogaster and D. simulans
      isofemale lines exhibited a wide range in the number of missing bristles. By
      contrast, D. mauritiana and D. sechellia lines showed almost no reduction in
      bristle number in hybrids with D. melanogaster. Genetic analysis showed that the
      D. simulans X chromosome confers a large effect on hybrid bristle loss, although
      X-autosome interaction may be involved. This suggests that at least one genetic
      factor contributing to hybrid anomalies arose recently on a D. simulans X
      chromosome. Moreover, the results indicate sex dependency: the male hybrids were
      more susceptible to bristle loss than the female hybrids were. Use of cell type
      markers suggests that the defect does not lie in cell fate decisions during
      bristle development, but in the maintenance of neural fate and/or differentiation
      of the descendants of sensory mother cells.

PMID- 9649533
TI  - Chromosome rearrangements induce both variegated and reduced, uniform expression
      of heterochromatic genes in a development-specific manner.
AB  - In Drosophila melanogaster, chromosome rearrangements that juxtapose euchromatin
      and heterochromatin can result in position effect variegation (PEV), the variable
      expression of heterochromatic and euchromatic genes in the vicinity of the novel
      breakpoint. We examined PEV of the heterochromatic light (lt) and concertina
      (cta) genes in order to investigate potential tissue or developmental differences
      in chromosome structure that might be informative for comparing the mechanisms of
      PEV of heterochromatic and euchromatic genes. We employed tissue pigmentation and
      in situ hybridization to RNA to assess expression of lt in individual cells of
      multiple tissues during development. Variegation of lt was induced in the adult
      eye, larval salivary glands and larval Malpighian tubules for each of three
      different chromosome rearrangements. The relative severity of the effect in these
      tissues was not tissue-specific but rather was characteristic of each
      rearrangement. Surprisingly, larval imaginal discs did not exhibit variegated lt
      expression. Instead, a uniform reduction of the lt transcript was observed, which
      correlated in magnitude with the degree of variegation. The same results were
      obtained for cta expression. These two distinct effects of rearrangements on
      heterochromatic gene expression correlated with the developmental stage of the
      tissue. These results have implications for models of heterochromatin formation
      and the nuclear organization of chromosomes during development and
      differentiation.

PMID- 9649534
TI  - Drosophila hormone receptor 38 functions in metamorphosis: a role in adult
      cuticle formation.
AB  - DHR38 is a member of the steroid receptor superfamily in Drosophila homologous to
      the vertebrate NGFI-B-type orphan receptors. In addition to binding to specific
      response elements as a monomer, DHR38 interacts with the USP component of the
      ecdysone receptor complex in vitro, in yeast and in a cell line, suggesting that
      DHR38 might modulate ecdysone-triggered signals in the fly. We characterized the
      molecular structure and expression of the Dhr38 gene and initiated an in vivo
      analysis of its function(s) in development. The Dhr38 transcription unit spans
      more than 40 kb in length, includes four introns, and produces at least four mRNA
      isoforms differentially expressed in development; two of these are greatly
      enriched in the pupal stage and encode nested polypeptides. We characterized four
      alleles of Dhr38: a P-element enchancer trap line, l(2)02306, which shows
      exclusively epidermal staining in the late larval, pre-pupal and pupal stages,
      and three EMS-induced alleles. Dhr38 alleles cause localized fragility and
      rupturing of the adult cuticle, demonstrating that Dhr38 plays an important role
      in late stages of epidermal metamorphosis.

PMID- 9649535
TI  - Autoregulation of transformer-2 alternative splicing is necessary for normal male
      fertility in Drosophila.
AB  - In the male germline of Drosophila the transformer-2 protein is required for
      differential splicing of pre-mRNAs from the exuperantia and att genes and
      autoregulates alternative splicing of its own pre-mRNA. Autoregulation of TRA-2
      splicing results in production of two mRNAs that differ by the splicing/retention
      of the M1 intron and encode functionally distinct protein isoforms. Splicing of
      the intron produces an mRNA encoding TRA-2(226), which is necessary and
      sufficient for both male fertility and regulation of downstream target RNAs. When
      the intron is retained, an mRNA is produced encoding TRA-2(179), a protein with
      no known function. We have previously shown that repression of M1 splicing is
      dependent on TRA-2(226), suggesting that this protein quantitatively limits its
      own expression through a negative feedback mechanism at the level of splicing.
      Here we examine this idea, by testing the effect that variations in the level of
      tra-2 expression have on the splicing of M1 and on male fertility. Consistent
      with our hypothesis, we observe that as tra-2 gene dosage is increased, smaller
      proportions of TRA-2(226) mRNA are produced, limiting expression of this isoform.
      Feedback regulation is critical for male fertility, since it is significantly
      decreased by a transgene in which repression of M1 splicing cannot occur and TRA
      2(226) mRNA is constitutively produced. The effect of this transgene becomes more
      severe as its dosage is increased, indicating that fertility is sensitive to an
      excess of TRA-2(226). Our results suggest that autoregulation of TRA-2(226)
      expression in male germ cells is necessary for normal spermatogenesis.

PMID- 9649536
TI  - Female genotypes affect sperm displacement in Drosophila.
AB  - Differential success of sperm is likely to be an important component of fitness.
      Extensive variation among male genotypes in competitive success of sperm in
      multiply mated females has been documented for Drosophila melanogaster. However,
      virtually all previous studies considered the female to be a passive vessel.
      Nevertheless, under certain conditions female fitness could be determined by her
      role in mediating use of sperm from multiple males. Here we ask whether females
      differ among genotypes in their tendency to exhibit last-male precedence.
      Competition of sperm from two tester male genotypes (bwD and B3-09, a third
      chromosome isogenic line from Beltsville, MD) was quantified by doubly mating
      female lines that had been rendered homozygous for X, second, or third
      chromosomes isolated from natural populations. The composite sperm displacement
      parameter, P2', was highly heterogeneous among lines, whether or not viability
      effects were compensated, implying the presence of polymorphic genes affecting
      access of sperm to eggs. Genetic variation of this type is completely neutral in
      the absence of pleiotropy or interaction between variation in the two sexes.

PMID- 9649537
TI  - Isolation of the gene encoding the Drosophila melanogaster homolog of the
      Saccharomyces cerevisiae GCN2 eIF-2alpha kinase.
AB  - Genomic and cDNA clones homologous to the yeast GCN2 eIF-2alpha kinase (yGCN2)
      were isolated from Drosophila melanogaster. The identity of the Drosophila GCN2
      (dGCN2) gene is supported by the unique combination of sequence encoding a
      protein kinase catalytic domain and a domain homologous to histidyl-tRNA
      synthetase and by the ability of dGCN2 to complement a deletion mutant of the
      yeast GCN2 gene. Complementation of Deltagcn2 in yeast by dGCN2 depends on the
      presence of the critical regulatory phosphorylation site (serine 51) of eIF
      2alpha. dGCN2 is composed of 10 exons encoding a protein of 1589 amino acids.
      dGCN2 mRNA is expressed throughout Drosophila development and is particularly
      abundant at the earliest stages of embryogenesis. The dGCN2 gene was
      cytogenetically and physically mapped to the right arm of the third chromosome at
      100C3 in STS Dm2514. The discovery of GCN2 in higher eukaryotes is somewhat
      unexpected given the marked differences between the amino acid biosynthetic
      pathways of yeast vs. Drosophila and other higher eukaryotes. Despite these
      differences, the presence of GCN2 in Drosophila suggests at least partial
      conservation from yeast to multicellular organisms of the mechanisms responding
      to amino acid deprivation.

PMID- 9649538
TI  - Nonneutral evolution and differential mutation rate of gender-associated
      mitochondrial DNA lineages in the marine mussel Mytilus.
AB  - Mussels have two types of mitochondrial DNA (mtDNA). The M type is transmitted
      paternally, and the F type is transmitted maternally. To test hypotheses of the
      molecular evolution of both mtDNA genomes, 50 nucleotide sequences were obtained
      for 396 bp of the COIII gene of European populations of Mytilus edulis and the
      Atlantic and Mediterranean forms of M. galloprovincialis. Analysis based on the
      proportion of synonymous and nonsynonymous substitutions indicate that mtDNA is
      evolving in a non-neutral and complex fashion. Previous studies on American
      mussels demonstrated that the F genome experiences a higher purifying selection
      and that the M genome evolves faster. Here we show that these patterns also hold
      in European populations. However, in contrast to American populations, where an
      excess of replacement substitution between F and M lineages has been reported, a
      significant excess of replacement polymorphism within mtDNA lineages is observed
      in European populations of M. galloprovincialis. European populations also show
      an excess of replacement polymorphism within the F but not within the M genome
      with respect to American M. trossulus, as well as a consistent pattern of excess
      of rare variants in both F and M genomes. These results are consistent with a
      nearly neutral model of molecular evolution and a recent relaxation of selective
      constraints on European mtDNA. Levels of diversity are significantly higher for
      the M than F genome, and the M genome also accumulates synonymous and
      nonsynonymous substitutions at a higher rate, in contrast with earlier reports
      where no difference for the synonymous rate was observed. It is suggested that a
      subtle balance between relaxed selection and a higher mutation rate explains the
      faster evolutionary rate of the M lineage.

PMID- 9649539
TI  - Linkage relationships and haplotype polymorphism among cichlid Mhc class II B
      loci.
AB  - The species flocks of cichlid fishes in the Great East African Lakes are
      paradigms of adaptive radiation and hence, of great interest to evolutionary
      biologists. Phylogenetic studies of these fishes have, however, been hampered by
      the lack of suitable polymorphic markers. The genes of the major
      histocompatibility complex hold the promise to provide, through their extensive
      polymorphism, a large number of such markers, but their use has been hampered by
      the complexity of the genetic system and the lack of definition of the individual
      loci. In this study we take the first substantial step to alleviate this problem.
      Using a combination of methods, including the typing of single sperm cells, gyno-
      or androgenetic individuals, and haploid embryos, as well as sequencing of class
      II B restriction fragments isolated from gels for Southern blots, we identify the
      previously characterized homology groups as distinct loci. At least 17
      polymorphic class II B loci, all of which are presumably transcribed, have been
      found among the different species studied. Most of these loci are shared across
      the various cichlid species and genera. The number of loci per haplotype varies
      from individual to individual, ranging from 1 to 13. A total of 21 distinct
      haplotypes differing in the number of loci they carry has thus far been
      identified. All the polymorphic loci are part of the same cluster in which,
      however, distances between at least some of the loci (as indicated by
      recombination frequencies) are relatively large. Both the individual loci and the
      haplotypes can now be used to study phylogenetic relationships among the members
      of the species flocks and the mode in which speciation occurs during adaptive
      radiation.

PMID- 9649540
TI  - Inference of population history using a likelihood approach.
AB  - We introduce an approach to revealing the likelihood of different population
      histories that utilizes an explicit model of sequence evolution for the DNA
      segment under study. Based on a phylogenetic tree reconstruction method we show
      that a Tamura-Nei model with heterogeneous mutation rates is a fair description
      of the evolutionary process of the hypervariable region I of the mitochondrial
      DNA from humans. Assuming this complex model still allows the estimation of
      population history parameters, we suggest a likelihood approach to conducting
      statistical inference within a class of expansion models. More precisely, the
      likelihood of the data is based on the mean pairwise differences between DNA
      sequences and the number of variable sites in a sample. The use of likelihood
      ratios enables comparison of different hypotheses about population history, such
      as constant population size during the past or an increase or decrease of
      population size starting at some point back in time. This method was applied to
      show that the population of the Basques has expanded, whereas that of the Biaka
      pygmies is most likely decreasing. The Nuu-Chah-Nulth data are consistent with a
      model of constant population.

PMID- 9649541
TI  - A rank-based nonparametric method for mapping quantitative trait loci in outbred
      half-sib pedigrees: application to milk production in a granddaughter design.
AB  - We describe the development of a multipoint nonparametric quantitative trait loci
      mapping method based on the Wilcoxon rank-sum test applicable to outbred half-sib
      pedigrees. The method has been evaluated on a simulated dataset and its
      efficiency compared with interval mapping by using regression. It was shown that
      the rank-based approach is slightly inferior to regression when the residual
      variance is homoscedastic normal; however, in three out of four other scenarios
      envisaged, i.e., residual variance heteroscedastic normal, homoscedastic skewed,
      and homoscedastic positively kurtosed, the latter outperforms the former one.
      Both methods were applied to a real data set analyzing the effect of bovine
      chromosome 6 on milk yield and composition by using a 125-cM map comprising 15
      microsatellites and a granddaughter design counting 1158 Holstein-Friesian sires.

PMID- 9649542
TI  - Quantitative trait locus mapping in dairy cattle by means of selective milk DNA
      pooling using dinucleotide microsatellite markers: analysis of milk protein
      percentage.
AB  - "Selective DNA pooling" accomplishes quantitative trait locus (QTL) mapping
      through densitometric estimates of marker allele frequencies in pooled DNA
      samples of phenotypically extreme individuals. With poly(TG) microsatellites,
      such estimates are confounded by "shadow" ("stutter") bands. A correction
      procedure was developed on the basis of an observed linear regression between
      shadow band intensity and allele TG repeat number. Using this procedure, a
      selective DNA pooling study with respect to milk protein percentage was
      implemented in Israel-Holstein dairy cattle. Pools were prepared from milk
      samples of high and low daughters of each of seven sires and genotyped with
      respect to 11 markers. Highly significant associations with milk protein
      percentage were found for 5 of the markers; 4 of these markers confirmed previous
      reports. Selective DNA pooling accessed 80.6 and 48.3%, respectively, of the
      information that would have been available through individual selective
      genotyping or total population genotyping. In effect, the statistical power of
      45,600 individual genotypings was obtained from 328 pool genotypings. This
      methodology can make genome-wide mapping of QTL accessible to moderately sized
      breeding organizations.

PMID- 9649543
TI  - Characterization of Soymar1, a mariner element in soybean.
AB  - Mariner elements, a family of DNA-mediated transposable elements with short,
      inverted terminal repeats, have been reported in a wide variety of arthropods, as
      well as planarians, nematodes, and humans. No such element has been reported in a
      plant. Here we report a mariner element in the plant soybean (Glycine max (L.)
      Merr.). Although this sequence belongs to the mariner family, it is clearly
      distinct from previously reported mariner-like elements, as well as from the Tc1
      transposon family. Novel aspects of its sequence could be useful as a starting
      point to identify mariner-like elements in new organisms, and it may prove useful
      in creating a transformation vector for plants.

PMID- 9649544
TI  - Characterization of an unstable allele of the Arabidopsis HY4 locus.
AB  - The Arabidopsis HY4 gene encodes the nonessential blue light photoreceptor CRY1.
      Loss-of-function hy4 mutants have an elongated hypocotyl phenotype after
      germination under blue light. We previously analyzed 20 independent hy4 alleles
      produced by fast neutron mutagenesis. These alleles were grouped into two classes
      based on their genetic behavior and corresponding deletion size: (1) null hy4
      alleles that were semidominant over wild type and contained small or moderate
      sized deletions at HY4 and (2) null hy4 alleles that were recessive lethal and
      contained large HY4 deletions. Here we describe one additional fast neutron hy4
      mutant, B144, that did not fall into either of these two classes. Mutant B144 was
      isolated as a heterozygote with an intermediate hy4 phenotype. One allele from
      this mutant, hy4-B144(Delta), contains a large deletion at HY4 and is recessive
      lethal. The other allele from this mutant, HY4-B144*, appears to be intact and
      functional but is unstable and spontaneously converts to a nonfunctional hy4
      allele. In addition, HY4-B144* is lethal in homozygotes and suppresses local
      recombination. We discuss genetic and epigenetic mechanisms that may account for
      the unusual behavior of the HY4-B144* allele.

PMID- 9649545
TI  - Molecular characterization of S locus genes, SLG and SRK, in a pollen-recessive
      self-incompatibility haplotype of Brassica rapa L.
AB  - In Brassica species that exhibit self-incompatibility, two genes, SLG and SRK, at
      the S locus are involved in the recognition reaction with self and non-self
      pollen. From a pollen-recessive S29 haplotype of Brassica rapa, both cDNA and
      genomic DNA clones for these two genes were isolated and characterized. The
      nucleotide sequence for the S domain of SRK29 showed a high degree of similarity
      with that of SLG29, and they belong to Class II type. RNA gel blot analysis
      showed that the transcript of SLG29 consisted of the first and second exons, and
      no other transcript containing any part of the intron sequence was detected.
      Because no transmembrane domain was encoded by the second exon of SLG29, SLG29
      was designated a secreted type glycoprotein. SLGs of two other pollen-recessive
      haplotypes, S40 and S44, of B. rapa also had a similar structure to that of
      SLG29. Previously, SLG2 from a pollen-recessive haplotype, S2, of Brassica
      oleracea was found to produce two different transcripts, one for the secreted
      type glycoprotein and the other for a putative membrane-anchored form of SLG.
      Therefore, the nature of these SLGs from pollen-recessive haplotypes of B. rapa
      is different from that of SLG2 of B. oleracea.

PMID- 9649546
TI  - The expected number of heterozygous sites in a subdivided population.
AB  - A simple, exact formula is derived for the expected number of heterozygous sites
      per individual at equilibrium in a subdivided population. The model of infinitely
      many neutral sites is posited; the linkage map is arbitrary. The monoecious,
      diploid population is subdivided into a finite number of panmictic colonies that
      exchange gametes. The backward migration matrix is arbitrary, but time
      independent and ergodic (i.e., irreducible and aperiodic). With suitable
      weighting, the expected number of heterozygous sites is 4Neu, where Ne denotes
      the migration effective population number and u designates the total mutation
      rate per gene (or DNA sequence). For diploid migration, this formula is a good
      approximation if Ne >> 1.

PMID- 9649547
TI  - On the sampling variance of intraclass correlations and genetic correlations.
AB  - Widely used standard expressions for the sampling variance of intraclass
      correlations and genetic correlation coefficients were reviewed for small and
      large sample sizes. For the sampling variance of the intraclass correlation, it
      was shown by simulation that the commonly used expression, derived using a first
      order Taylor series performs better than alternative expressions found in the
      literature, when the between-sire degrees of freedom were small. The expressions
      for the sampling variance of the genetic correlation are significantly biased for
      small sample sizes, in particular when the population values, or their estimates,
      are close to zero. It was shown, both analytically and by simulation, that this
      is because the estimate of the sampling variance becomes very large in these
      cases due to very small values of the denominator of the expressions. It was
      concluded, therefore, that for small samples, estimates of the heritabilities and
      genetic correlations should not be used in the expressions for the sampling
      variance of the genetic correlation. It was shown analytically that in cases
      where the population values of the heritabilities are known, using the estimated
      heritabilities rather than their true values to estimate the genetic correlation
      results in a lower sampling variance for the genetic correlation. Therefore, for
      large samples, estimates of heritabilities, and not their true values, should be
      used.

PMID- 9649548
TI  - Correlation between the substitution rate and rate variation among sites in
      protein evolution.
AB  - It is well known that the rate of amino acid substitution varies among different
      proteins and among different sites of a protein. It is, however, unclear whether
      the extent of rate variation among sites of a protein and the mean substitution
      rate of the protein are correlated. We used two approaches to analyze orthologous
      protein sequences of 51 nuclear genes of vertebrates and 13 mitochondrial genes
      of mammals. In the first approach, no assumptions of the distribution of the rate
      variation among sites were made, and in the second approach, the gamma
      distribution was assumed. Through both approaches, we found a negative
      correlation between the extent of among-site rate variation and the average
      substitution rate of a protein. That is, slowly evolving proteins tend to have a
      high level of rate variation among sites, and vice versa. We found this
      observation consistent with a simple model of the neutral theory where most sites
      are either invariable or neutral. We conclude that the correlation is a general
      feature of protein evolution and discuss its implications in statistical tests of
      positive Darwinian selection and molecular time estimation of deep divergences.

PMID- 9649549
TI  - Fallen arches, or how the vertebrate got its head.

PMID- 9649550
TI  - AZT treatment induces molecular and ultrastructural oxidative damage to muscle
      mitochondria. Prevention by antioxidant vitamins.
AB  - AIDS patients who receive zidovudine (AZT) frequently suffer from myopathy. This
      has been attributed to mitochondrial (mt) damage, and specifically to the loss of
      mtDNA. This study examines whether AZT causes oxidative damage to DNA in patients
      and to skeletal muscle mitochondria in mice, and whether this damage may be
      prevented by supranutritional doses of antioxidant vitamins. Asymptomatic HIV
      infected patients treated with AZT have a higher urinary excretion (355+/-100
      pmol/kg/d) of 8-oxo-7, 8-dihydro-2'-deoxyguanosine (8-oxo-dG) (a marker of
      oxidative damage to DNA) than untreated controls (asymptomatic HIV-infected
      patients) (182+/-29 pmol/kg/d). This was prevented (110+/-79 pmol/kg/d) by
      simultaneous oral treatment with AZT plus antioxidant vitamins (C and E). Mice
      treated with AZT also had a significantly higher urinary excretion of 8-oxo-dG
      than controls. Skeletal muscle mtDNA of mice treated with AZT had more 8-oxo-dG
      than controls. mt lipoperoxidation was also increased and skeletal muscle
      glutathione was oxidized. These effects may be due to an increased peroxide
      production by muscle mitochondria of AZT-treated animals. Dietary supplements
      with vitamins C and E at supranutritional doses protect against oxidative damage
      to skeletal muscle mitochondria caused by AZT.

PMID- 9649551
TI  - Abnormalities of nasal potential difference measurement in Liddle's syndrome.
AB  - In Liddle's syndrome, a rare inherited form of hypertension, epithelial sodium
      channel mutations appear to cause high blood pressure by increasing sodium
      reabsorption through sodium channels in the renal distal tubule. This increase in
      channel activity has not been confirmed previously by in vivo measurement. We
      have made transnasal potential difference measurements (effective in detection of
      increased sodium channel activity in cystic fibrosis) in three brothers with
      genetically proven Liddle's syndrome, their unaffected sister, and 40
      normotensive controls. Maximum potential difference after 2 wk off treatment in
      the affected brothers was -30.4+/-1.2 mV (values mean+/-SD, lumen-negative with
      respect to submucosa) and was significantly more lumen-negative than that of the
      control group (-18.6+/-6.8 mV, P = 0.0228) or the unaffected sister (-18.25 mV, P
      < 0.01). The change in potential difference after topical application of 10(-)4 M
      amiloride was greater in the Liddle's patients, 14.0+/-2.1 mV, than in controls
      (7.9+/-3.9 mV, P = 0.0126) or the unaffected sister (5.5 mV, P < 0.05). This is
      the first in vivo demonstration of increased sodium channel activity in Liddle's
      syndrome. If these results are confirmed in other kindreds with this condition,
      then nasal potential difference measurements could provide a simple clinical test
      for Liddle's syndrome.

PMID- 9649552
TI  - The amiloride-inhibitable Na+ conductance is reduced by the cystic fibrosis
      transmembrane conductance regulator in normal but not in cystic fibrosis airways.
AB  - Cystic fibrosis (CF) airway cells, besides their well-known defect in cAMP
      dependent Cl- conductance, are characterized by an enhanced Na+ conductance. In
      this study we have examined the Na+ conductance in human respiratory tract by
      measuring transepithelial voltage and resistance (Vte, Rte) and by assessing
      membrane voltages (Vm) of freshly isolated airway epithelial cells from CF and
      non-CF patients. Basal amiloride inhibitable (10 micromol/liter) equivalent short
      circuit current (Isc = Vte/Rte) was significantly increased in CF compared with
      non-CF tissues. After stimulation by forskolin (10 micromol/liter) a significant
      depolarization of Vm corresponding to the cAMP-dependent activation of a Cl-
      conductance was observed in non-CF but not in CF airway cells. In non-CF tissue
      but not in CF tissue the effects of amiloride and N-methyl-D-glucamine on Vm were
      attenuated in the presence of forskolin. Also the amiloride-inhibitable Isc was
      significantly reduced by forskolin (1 micromol/liter) and isobutylmethylxanthine
      (IBMX; 100 micromol/liter) only in non-CF tissue. We conclude that cystic
      fibrosis transmembrane conductance regulator acts as a downregulator of
      epithelial Na+ channels in human airways. This downregulation of epithelial Na+
      channels is absent in CF airways, leading to hyperabsorption and to the
      characteristic increase in mucus viscosity.

PMID- 9649553
TI  - Role of Endothelin-1/Endothelin-A receptor-mediated signaling pathway in the
      aortic arch patterning in mice.
AB  - The intercellular signaling mediated by endothelins and their G protein-coupled
      receptors has recently been shown to be essential for the normal embryonic
      development of subsets of neural crest cell derivatives. Endothelin-1 (ET-1) is
      proteolytically generated from its inactive precursor by endothelin-converting
      enzyme-1 (ECE-1) and acts on the endothelin-A (ETA) receptor. Genetic disruption
      of this ET-1/ECE-1/ETA pathway results in defects in branchial arch- derived
      craniofacial tissues, as well as defects in cardiac outflow and great vessel
      structures, which are derived from cephalic (cardiac) neural crest. In this
      study, in situ hybridization of ETA-/- and ECE-1(-)/- embryos with a cardiac
      neural crest marker, cellular retinoic acid-binding protein-1, shows that the
      migration of neural crest cells from the neural tube to cardiac outflow tract is
      not affected in these embryos. Immunostaining of an endothelial marker, platelet
      endothelial cell adhesion molecule CD-31, shows that the initial formation of the
      branchial arch arteries is not disturbed in ETA-/- or ECE-1(-)/- embryos. To
      visualize the subsequent patterning of arch vessels in detail, we generated ETA-/
      or ECE-1(-)/- embryos that expressed an SM22alpha-lacZ marker transgene in
      arterial smooth muscle cells. Wholemount X-gal staining of these mutant embryos
      reveals that the abnormal regression and persistence of specific arch arteries
      results in disturbance of asymmetrical remodeling of the arch arteries. These
      defects include abnormal regression of arch arteries 4 and 6, enlargement of arch
      artery 3, and abnormal persistence of the bilateral ductus caroticus and right
      dorsal aorta. These abnormalities eventually lead to various types of great
      vessel malformations highly similar to those seen in neural crest-ablated chick
      embryos and human congenital cardiac defects. This study demonstrates that ET
      1/ETA-mediated signaling plays an essential role in a complex process of aortic
      arch patterning by affecting the postmigratory cardiac neural crest cell
      development.

PMID- 9649554
TI  - Absence of functional receptors for parathyroid hormone and parathyroid hormone
      related peptide in Blomstrand chondrodysplasia.
AB  - We report the absence of functional parathyroid hormone (PTH)/PTH-related peptide
      (PTHrP) receptors (PTH/PTHrP receptor) in Blomstrand chondrodysplasia, a genetic
      disorder characterized by advanced endochondral bone maturation. Analysis of
      PTH/PTHrP receptor genomic DNA from a patient with Blomstrand chondrodysplasia
      demonstrated that the patient was heterozygous for a point mutation (G--> A
      substitution at nucleotide 1176) inherited from the mother. Analysis of PTH/PTHrP
      receptor cDNA demonstrated that: (a) this point mutation caused the deletion of
      the first 11 amino acids of exon M5 (encoding the fifth transmembrane domain of
      the receptor), resulting from the use of a novel splice site created by the base
      substitution; (b) the mutant receptor was well expressed in COS-7 cells, but did
      not bind PTH or PTHrP, and failed to induce detectable stimulation of either cAMP
      or inositol phosphate production in response to these ligands; and (c) the
      paternal allele was not expressed. Thus, only the abnormal and nonfunctional
      PTH/PTHrP receptors encoded by the maternal allele were expressed by chondrocytes
      from this patient. In view of the known role played by the PTH/PTHrP receptor in
      bone and cartilage development, these results strongly support the conclusion
      that the absence of functional PTH/ PTHrP receptors is responsible for the
      skeletal abnormalities seen in Blomstrand chondrodysplasia, abnormalities that
      are the mirror image of those observed in Jansen's chondrodysplasia. These
      findings emphasize the importance of signaling through this receptor in human
      fetal skeletal development.

PMID- 9649555
TI  - Exacerbation of antigen-induced arthritis in urokinase-deficient mice.
AB  - In rheumatoid arthritis, synovial expression of urokinase (uPA) activity is
      greatly increased (Busso, N., V. Peclat, A. So, and A. -P. Sappino. 1997. Ann.
      Rheum. Dis. 56:550- 557). We report the same effect in murine antigen-induced
      arthritis. uPA-mediated plasminogen activation in arthritic joints may have
      deleterious effects via degradation of cartilage and bone matrix proteins as well
      as beneficial effects via fibrin degradation. We evaluated these contrasting
      effects in vivo by analyzing the phenotype of uPA-deficient (uPA-/-) and control
      mice during antigen-induced arthritis. Joint inflammation was comparable in both
      groups up to day 3 and subsequently declined in control mice, remaining
      significantly elevated in uPA-/- mice on days 10 and 30 after arthritis onset.
      Likewise, synovial thickness was markedly increased in uPA-deficient mice
      persisting for up to 2 mo, whereas it subsided in control animals. Bone erosion
      was exacerbated in uPA-/- mice on day 30. By contrast, no difference in articular
      cartilage proteoglycan content was found between both groups. Significantly
      increased accumulation of fibrin was observed by day 30 in arthritic joints of
      uPA-/- mice. We hypothesized that synovial fibrin deposition plays a role in
      joint inflammation. Accordingly, defibrinogenation of uPA-/- mice by ancrod
      significantly decreased the sustained joint inflammation. All the above
      observations were reproducible in plasminogen-deficient (Pln-/-) mice. In
      conclusion, synovial fibrin deposition plays a role as a nonimmunological
      mechanism which sustains chronic arthritis.

PMID- 9649556
TI  - Induction of B cell responses in the stomach of Helicobacter pylori- infected
      subjects after oral cholera vaccination.
AB  - We have evaluated the possibility of inducing antibody responses locally in the
      human stomach as a prerequisite for the development of a vaccine against
      Helicobacter pylori. Both H. pylori-infected and noninfected subjects were
      immunized with an oral B subunit whole cell (BS-WC) cholera vaccine, and total
      and vaccine-specific antibody-secreting cells (ASC) were determined by the enzyme
      linked immunospot (ELISPOT) technique in cells isolated from the antrum and
      duodenum, respectively, before and after vaccination. Most of the subjects
      responded to the vaccination with high frequencies of vaccine-specific ASCs in
      the duodenum as well as high-serum antibody titers, and no significant
      differences were seen in the responses between H. pylori- infected and
      noninfected subjects. When studying the gastric mucosa, on the other hand, there
      were dramatic differences between the H. pylori-infected and the noninfected
      subjects. Thus, whereas none of the noninfected subjects responded to the
      immunization in antrum, most of the H. pylori-infected subjects had high
      frequencies of vaccine-specific ASCs in this location after vaccination.
      Furthermore, the H. pylori-infected subjects had strikingly higher (as a mean 80
      fold) frequencies of total IgA-secreting cells in antrum than the noninfected
      subjects, whereas the frequencies of total IgA-secreting cells in the duodenum
      were comparable between the groups. In conclusion, these results demonstrate the
      possibility of inducing antibody responses locally in the gastric mucosa of H.
      pylori-infected individuals, a finding with obvious implications for the future
      development of a therapeutic vaccine against H. pylori.

PMID- 9649557
TI  - An aquaporin-2 water channel mutant which causes autosomal dominant nephrogenic
      diabetes insipidus is retained in the Golgi complex.
AB  - Mutations in the aquaporin-2 (AQP2) water channel gene cause autosomal recessive
      nephrogenic diabetes insipidus (NDI). Here we report the first patient with an
      autosomal dominant form of NDI, which is caused by a G866A transition in the AQP2
      gene of one allele, resulting in a E258K substitution in the C-tail of AQP2. To
      define the molecular cause of NDI in this patient, AQP2-E258K was studied in
      Xenopus oocytes. In contrast to wild-type AQP2, AQP2-E258K conferred a small
      increase in water permeability, caused by a reduced expression at the plasma
      membrane. Coexpression of wild-type AQP2 with AQP2-E258K, but not with an AQP2
      mutant in recessive NDI (AQP2-R187C), revealed a dominant-negative effect on the
      water permeability conferred by wild-type AQP2. The physiologically important
      phosphorylation of S256 by protein kinase A was not affected by the E258K
      mutation. Immunoblot and microscopic analyses revealed that AQP2-E258K was, in
      contrast to AQP2 mutants in recessive NDI, not retarded in the endoplasmic
      reticulum, but retained in the Golgi compartment. Since AQPs are thought to
      tetramerize, the retention of AQP2-E258K together with wild-type AQP2 in mixed
      tetramers in the Golgi compartment is a likely explanation for the dominant
      inheritance of NDI in this patient.

PMID- 9649558
TI  - Dietary supplement with vitamin C prevents nitrate tolerance.
AB  - Enhanced formation of superoxide radicals has been proposed to play a major role
      in the development of nitrate tolerance in humans. We tested the effects of
      vitamin C (Vit-C) supplementation on glyceroltrinitrate (GTN)-induced hemodynamic
      effects during 3-d nonintermittent transdermal administration of GTN (0.4 mg/h)
      in nine healthy subjects. Tolerance development was monitored by changes in
      arterial pressure, dicrotic digital pulse pressure, and heart rate. Studies with
      GTN, Vit-C, or GTN/Vit-C were successively carried out at random in three
      different series in the same subjects. GTN treatment caused an immediate rise in
      arterial conductivity (a/b ratio of dicrotic pulse), but within 2 d of initiating
      GTN, the a/b ratio progressively decreased and reached basal levels. In addition,
      there was a progressive loss of the orthostatic decrease in blood pressure.
      However, coadministration of Vit-C and GTN fully maintained the GTN-induced
      changes in the orthostatic blood pressure, and the rise of a/b ratio was
      augmented by 310% for the duration of the test period. Changes in vascular
      tolerance in GTN-treated subjects were paralleled by upregulation of the activity
      of isolated platelets, which was also reversed by Vit-C administration. These
      findings demonstrate that dietary supplementation with Vit-C eliminates vascular
      tolerance and concomitant upregulation of ex vivo-washed platelet activity during
      long-term nonintermittent administration of GTN in humans.

PMID- 9649559
TI  - In vivo phosphorylation of cardiac troponin I by protein kinase Cbeta2 decreases
      cardiomyocyte calcium responsiveness and contractility in transgenic mouse
      hearts.
AB  - Recently, it has been reported that the protein kinase C (PKC) beta isoform plays
      a critical role in the development of hypertrophy and heart failure. The purpose
      of the present study was to clarify the mechanism by which activation of PKCbeta
      led to depressed cardiac function. Thus, we used a PKCbeta2 overexpressing mouse,
      an animal model of heart failure, to examine mechanical properties and Ca2+
      signals of isolated left ventricular cardiomyocytes. The percentage of
      shortening, rate of shortening, and rate of relengthening of cardiomyocytes were
      markedly reduced in PKCbeta2 overexpression mice compared to wild-type control
      mice, although the baseline level and amplitude of Ca2+ signals were similar.
      These findings suggested a decreased myofilament responsiveness to Ca2+ in
      transgenic hearts. Therefore, the incorporation of [32P] inorganic phosphate into
      cardiac myofibrillar proteins was studied in Langendorff-perfused hearts. There
      was a significant increase in the degree of phosphorylation of troponin I in
      PKCbeta2-overexpressing transgenic mice. The depressed cardiomyocyte function
      improved after the superfusion of a PKCbeta selective inhibitor. These findings
      indicate that in vivo PKCbeta2-mediated phosphorylation of troponin I may
      decrease myofilament Ca2+ responsiveness, and thus causes cardiomyocyte
      dysfunction. Since chronic and excess activation of PKCbeta2 plays a direct and
      contributory role in the progression of cardiac dysfunction, the PKCbeta
      selective inhibitor may provide a new therapeutic modality in the setting of
      heart failure.

PMID- 9649560
TI  - In vivo analysis of Fas/FasL interactions in HIV-infected patients.
AB  - Recent insights into the pharmacological control of HIV replication and the
      molecular mechanisms of peripheral T cells homeostasis allowed us to investigate
      in vivo the mechanisms mediating T cell depletion in HIV-infected patients.
      Before the initiation of highly active antiretroviral therapy (HAART), a high
      degree of lymphoid tissue apoptosis is present, which is reduced upon HAART
      initiation (P < 0.001) and directly correlates with reduction of viral load and
      increases of peripheral T lymphocytes (P < 0.01). Because Fas/FasL interactions
      play a key role in peripheral T lymphocyte homeostasis, we investigated the
      susceptibility to Fas-mediated apoptosis in peripheral T lymphocytes and of FasL
      expression in lymphoid tissue before and during HAART. High levels of Fas
      susceptibility found in peripheral CD4 T lymphocytes before HAART were
      significantly reduced after HAART, coinciding with decreases in viral load (P =
      0.018) and increases in peripheral CD4 T lymphocyte counts (P < 0.01). However,
      the increased FasL expression in the lymphoid tissue of HIV-infected individuals
      was not reduced after HAART. These results demonstrate that lymphoid tissue
      apoptosis directly correlates with viral load and peripheral T lymphocyte
      numbers, and suggest that HIV-induced susceptibility to Fas-dependent apoptosis
      may play a key role in the regulation of T cell homeostasis in HIV-infected
      individuals.

PMID- 9649561
TI  - Immortalization of osteoclast precursors by targeting Bcl -XL and Simian virus 40
      large T antigen to the osteoclast lineage in transgenic mice.
AB  - Cellular and molecular characterization of osteoclasts (OCL) has been extremely
      difficult since OCL are rare cells, and are difficult to isolate in large
      numbers. We used the tartrate-resistant acid phosphatase promoter to target the
      bcl-XL and/or Simian Virus 40 large T antigen (Tag) genes to cells in the OCL
      lineage in transgenic mice as a means of immortalizing OCL precursors.
      Immunocytochemical studies confirmed that we had targeted Bcl-XL and/or Tag to
      OCL, and transformed and mitotic OCL were readily apparent in bones from both Tag
      and bcl-XL/Tag mice. OCL formation in primary bone marrow cultures from bcl-XL,
      Tag, or bcl-XL/Tag mice was twofold greater compared with that of nontransgenic
      littermates. Bone marrow cells from bcl-XL/Tag mice, but not from singly
      transgenic bcl-XL or Tag mice, have survived in continuous culture for more than
      a year. These cells form high numbers of bone-resorbing OCL when cultured using
      standard conditions for inducing OCL formation, with approximately 50% of the
      mononuclear cells incorporated into OCL. The OCL that form express calcitonin
      receptors and contract in response to calcitonin. Studies examining the
      proliferative capacity and the resistance of OCL precursors from these transgenic
      mice to apoptosis demonstrated that the increased numbers of OCL precursors in
      marrow from bcl-XL/Tag mice was due to their increased survival rather than an
      increased proliferative capacity compared with Tag, bcl-XL, or normal mice.
      Histomorphometric studies of bones from bcl-XL/Tag mice also confirmed that there
      were increased numbers of OCL precursors (TRAP + mononuclear cells) present in
      vivo. These data demonstrate that by targeting both bcl-XL and Tag to cells in
      the OCL lineage, we have immortalized OCL precursors that form bone-resorbing OCL
      with an efficiency that is 300-500 times greater than that of normal marrow.

PMID- 9649562
TI  - Role of interleukin 10 in specific immunotherapy.
AB  - The induction of allergen-specific anergy in peripheral T cells represents a key
      step in specific immunotherapy (SIT). Here we demonstrate that the anergic state
      results from increased IL-10 production. In bee venom (BV)-SIT the specific
      proliferative and cytokine responses against the main allergen, the phospholipase
      A2 (PLA), and T cell epitope-containing PLA peptides were significantly
      suppressed after 7 d of treatment. Simultaneously, the production of IL-10
      increased during BV-SIT. After 28 d of BV-SIT the anergic state was established.
      Intracytoplasmic cytokine staining of PBMC combined with surface marker detection
      revealed that IL-10 was produced initially by activated CD4(+)CD25(+), allergen
      specific T cells, and followed by B cells and monocytes. Neutralization of IL-10
      in PBMC fully reconstituted the specific proliferative and cytokine responses. A
      similar state of IL-10-associated T cell anergy, as induced in BV-SIT, was found
      in hyperimmune individuals who recently had received multiple bee stings. The
      addition of IL-10 to soluble CD40 ligand IL-4-stimulated PBMC or purified B cells
      inhibited the PLA-specific and total IgE and enhanced the IgG4 formation.
      Accordingly, increased IL-10 production by SIT causes specific anergy in
      peripheral T cells, and regulates specific IgE and IgG4 production toward normal
      IgG4-related immunity.

PMID- 9649563
TI  - Molecular defects in ferrochelatase in patients with protoporphyria requiring
      liver transplantation.
AB  - Protoporphyria is a genetic disorder in which a deficiency of mitochondrial
      ferrochelatase activity causes accumulation of protoporphyrin that produces
      severe liver damage in some patients. In this study, mutations of the
      ferrochelatase gene were examined in eight unrelated patients who had liver
      transplantation. RNA was prepared from liver and/ or lymphoblasts, and specific
      reverse transcriptase-nested polymerase chain reactions amplified and sequenced
      ferrochelatase cDNAs. Products shorter than normal resulted from an exon 3
      deletion in three patients, exon 10 deletion in two, exon 2 deletion in one, and
      deletion of five nucleotides in exon 5 in one. Sequence of normal-size products
      revealed no other mutations. Western blot showed a reduced quantity of normal
      size ferrochelatase protein in protoporphyria liver compared with normal liver
      (19-51%, mean 32% of normal). Levels of the mitochondrial protein F1-ATPase beta
      subunit were not decreased to a similar degree. Liver ferrochelatase activity was
      reduced more than could be explained by the decrease in ferrochelatase protein (4
      20%, mean 9% of normal). These results establish genetic heterogeneity in the
      most severe phenotype of protoporphyria. However, the gene mutations found share
      the property of causing a major structural alteration in the ferrochelatase
      protein.

PMID- 9649564
TI  - Interleukin-11 promotes T cell polarization and prevents acute graft-versus-host
      disease after allogeneic bone marrow transplantation.
AB  - Administration of IL-11 prevented lethal graft-versus-host disease (GVHD) in a
      murine bone marrow transplant (BMT) model (B6 --> B6D2F1) across MHC and minor H
      antigen barriers (survival at day 50: 90 vs 20%, P < 0.001). Surpisingly, IL-11
      administration polarized the donor T cell cytokine responses to host antigen
      after BMT with a 50% reduction in IFNgamma and IL-2 secretion and a 10-fold
      increase in IL-4. This polarization of T cell responses was associated with
      reduced IFNgamma serum levels and decreased IL-12 production in mixed lymphocyte
      cultures (MLC). In addition, IL-11 prevented small bowel damage and reduced serum
      endotoxin levels by 80%. Treatment with IL-11 also reduced TNFalpha serum levels
      and suppressed TNFalpha secretion by macrophages to LPS stimulation in vitro. IL
      11 thus decreased GVHD morbidity and mortality by three mechanisms: (a)
      polarization of donor T cells; (b) protection of the small bowel; and (c)
      suppression of inflammatory cytokines such as TNFalpha. We conclude that brief
      treatment with IL-11 may represent a novel strategy to prevent T cell-mediated
      inflammatory processes such as GVHD.

PMID- 9649565
TI  - Absence of polycythemia in a child with a unique erythropoietin receptor mutation
      in a family with autosomal dominant primary polycythemia.
AB  - Primary familial and congenital polycythemia (PFCP or familial erythrocytosis) is
      a rare proliferative disorder of erythroid progenitor cells, characterized by
      elevated erythrocyte mass and hemoglobin concentration, hypersensitivity of
      erythroid progenitors to erythropoietin (EPO), and autosomal dominant inheritance
      or sporadic occurrence. A number of EPO receptor (EPOR) mutations were found in
      subjects with PFCP; most of these mutations resulted in the truncation of the
      COOH-terminal of the EPOR protein. We studied a family with autosomal dominant
      inheritance of PFCP in which four subjects were affected in three generations. We
      screened the affected individuals for EPOR gene mutations using SSCP analysis and
      found a C5964G mutation in exon VIII that changes tyrosine codon 426 to a
      translation termination codon resulting in an EPOR protein truncated by 83 amino
      acids. The mutant C5964G-EPOR exhibited hypersensitive EPO-dependent
      proliferation compared to the wild-type EPOR when tested in a murine interleukin
      3-dependent myeloid cell line (FDC-P1). We also examined the segregation of the
      mutation with PFCP in the family and found that a child in the third generation
      inherited the mutation without having laboratory evidence of polycythemia.
      Further in vitro analysis of the erythroid progenitor cells of this affected
      child revealed that the progenitor cells were hypersensitive to EPO (a hallmark
      of PFCP) suggesting the presence of the disease at the level of progenitor cells.
      Failure of this child to develop polycythemia suggests the existence of as yet
      unidentified environmental or genetic factors that may suppress disease
      development.

PMID- 9649566
TI  - Type III hyperlipoproteinemia and spontaneous atherosclerosis in mice resulting
      from gene replacement of mouse Apoe with human Apoe*2.
AB  - To study isoform-specific effects of apolipoprotein E (apoE) in vivo, we
      generated mice with a human APOE*2 allele in place of the mouse Apoe gene via
      targeted gene replacement in embryonic stem cells. Mice expressing human apoE2
      (2/2) have virtually all the characteristics of type III hyperlipoproteinemia.
      Their plasma cholesterol and triglyceride levels are both twice to three times
      those in (normolipidemic) mice that are expressing human apoE3 (3/3) made in an
      identical manner. The 2/2 mice are markedly defective in clearing beta-migrating
      VLDL particles, and spontaneously develop atherosclerotic plaques, even on a
      regular diet. An atherogenic diet, high in fat and cholesterol, exacerbates
      development of atherosclerosis and xanthomas in the 2/2 mice. Thus, comparisons
      between the 2/2 and 3/3 mice unequivocally demonstrate that a single amino acid
      difference (Arg158 Cys) in the apoE protein is sufficient to cause type III HLP
      and spontaneous atherosclerosis in mice.

PMID- 9649567
TI  - Modulation of monocyte-endothelial cell interactions by platelet microparticles.
AB  - Platelets, activated by various agonists, produce microparticles (MP) from the
      plasma membrane, which are released into the extracellular space. Although the
      mechanism of MP formation has been clarified, their biological importance remains
      ill defined. We have recently shown that platelet-derived MP influence platelet
      and endothelial cell function. In this study, we have further examined the
      mechanism of cellular activation by platelet MP. To address the possibility that
      they may influence monocyte-endothelial interactions, we used an in vitro assay
      to examine their effects on the adhesion of monocytes to human umbilical vein
      endothelial cells (HUVEC). Platelet MP increased the adhesion of monocytes to
      HUVEC in a time- and dose-dependent manner. Maximal adhesion of monocytes to
      resting HUVEC was observed after 24 h of stimulation with MP. Similar kinetics
      were observed with U-937 (human promonocytic leukemia) cells, used as a model for
      the blood-borne monocyte. Maximal adhesion of resting monocytes to MP-stimulated
      HUVEC was observed after 5 h of stimulation with MP. The EC50s for MP-induced
      increases in HUVEC, monocyte, and U-937 cell adhesion is 8.74, 43.41, and 10.83
      microg/ml of MP protein, respectively. The induction of monocyte-endothelial
      adhesion was mimicked by arachidonic acid isolated from MP. The observed
      increased cellular adhesiveness correlated with MP-induced upregulation of cell
      adhesion molecules. MP-stimulated HUVEC increased intracellular cell adhesion
      molecule-1 (ICAM-1) but not vascular cell adhesion molecule-1 (VCAM-1), P-, or E
      selectin expression. Monocyte and U-937 lymphocyte function-associated antigen-1
      (CD11a/CD18) and macrophage antigen-1 (CD11b/ CD18, alpham/beta2) were both
      upregulated upon MP stimulation, but an increase in p150,95 (CD11c/CD18), very
      late antigen-1, or ICAM-1 expression was not observed. The functional importance
      of these changes was demonstrated with blocking antibodies. MP also induced the
      chemotaxis of U-937 cells in a dose-dependent manner with an EC50 of 4.40
      microg/ml of MP protein. Similarly, arachidonic acid isolated from MP mimicked
      the chemotactic response. A role for PKC was implicated in both adhesion and
      chemotaxis. GF 109203X, a specific inhibitor of PKC, significantly reduced
      monocyte-endothelial adhesion, as well as U-937 chemotaxis. The demonstration
      that platelet MP may modulate important aspects of endothelial and monocyte
      function provides a novel mechanism by which platelets may interact with such
      cells in human atherosclerosis and inflammation.

PMID- 9649568
TI  - The combined role of P- and E-selectins in atherosclerosis.
AB  - P- and E-selectins are adhesion molecules mediating the first step in leukocyte
      extravasation. Because their function in leukocyte adhesion is overlapping, we
      hypothesized that there might be a combined effect of these selectins on the
      development of atherosclerotic lesions. We bred P- and E-selectin-double
      deficient mice onto the low-density lipoprotein receptor (LDLR)-deficient
      background (LDLR-/- P/E-/-) and compared lesion development in these mice to that
      in mice wild type for both selectins (LDLR-/- P/E+/+). After 8 wk on atherogenic
      diet, the LDLR-/- P/E-/- mice developed fatty streaks in the aortic sinus that
      were five times smaller than those in LDLR-/- P/E+/+ mice. The density of
      macrophages in the fatty streaks was comparable between LDLR-/- P/E+/+ and LDLR-/
      P/E-/- mice. After 22 wk on the diet, the lesions spread throughout the aorta
      but this process was delayed in LDLR-/- P/E-/- mice. At 37 wk on diet, the
      lesions progressed to the fibrous plaque stage in both genotypes. However, the
      lesions in the aortic sinus in LDLR-/- P/E-/- mice were 40% smaller and less
      calcified than those of LDLR-/- P/E +/+ mice. Our results suggest that P- and E
      selectins together play an important role in both early and advanced stages of
      atherosclerotic lesion development.

PMID- 9649569
TI  - Regulatory mechanisms of growth hormone secretion are sexually dimorphic.
AB  - Sexually dimorphic growth hormone (GH) secretory pattern is important in the
      determination of gender-specific patterns of growth and metabolism in rats.
      Whether GH secretion in humans is also sexually dimorphic and the neuroendocrine
      mechanisms governing this potential difference are not fully established. We have
      compared pulsatile GH secretion profiles in young men and women in the baseline
      state and during a continuous intravenous infusion of recombinant human insulin
      like growth factor I (rhIGF-I). During the baseline study, men had large
      nocturnal GH pulses and relatively small pulses during the rest of the day. In
      contrast, women had more continuous GH secretion and more frequent GH pulses that
      were of more uniform size. The infusion of rhIGF-I (10 microg/kg/h) potently
      suppressed both spontaneous and growth hormone-releasing hormone (GHRH)-induced
      GH secretion in men. In women, however, rhIGF-I had less effect on pulsatile GH
      secretion and did not suppress the GH response to GHRH. These data demonstrate
      the existence of sexual dimorphism in the regulatory mechanisms involved in GH
      secretion in humans. The persistence of GH responses to GHRH in women suggests
      that negative feedback by IGF-I might be expressed, in part, through suppression
      of hypothalamic GHRH.

PMID- 9649570
TI  - Integrin-dependent homotypic adhesion of neutrophils. Arachidonic acid activates
      Raf-1/Mek/Erk via a 5-lipoxygenase- dependent pathway.
AB  - AA stimulates integrin-dependent neutrophil adhesion, a critical early step in
      acute inflammation. However, neither the signaling pathway(s) of AA-stimulated
      adhesion, nor whether AA acts directly or through the generation of active
      metabolites, has been elucidated. Previously, we have observed a tight
      association between neutrophil Erk activation and homotypic adhesion in response
      to chemoattractants acting through G protein-linked receptors. We now report a
      similar association between homotypic adhesion and Erk activation in response to
      AA. Erk activation was cyclooxygenase independent and required AA metabolism to
      5(S)- hydroperoxyeicosatetraenoic acid (5-HpETE) via 5-lipoxygenase, but not the
      further lipoxygenase-dependent metabolism of 5-HpETE to leukotrienes. AA
      stimulation of Erk was accompanied by Raf-1 activation and was sensitive to
      inhibitors of Raf-1 and Mek. Whereas activation of Erk by AA was pertussis toxin
      sensitive, [3H]-AA binding to neutrophils was not saturable, suggesting that an
      AA metabolite activates a G protein. Consistent with this hypothesis, Erk
      activation by 5(S)-hydroxyeicosatetraenoic acid (5-HETE; lipoxygenase-independent
      metabolite of 5-HpETE) was also pertussis toxin sensitive. These data suggest
      that a 5-lipoxygenase metabolite of AA, e.g., 5-HETE, is released from AA-treated
      cells to engage a plasma membrane-associated, pertussis toxin-sensitive, G
      protein-linked receptor, leading to activation of Erk and adhesion via the Raf
      1/Mek signal transduction pathway.

PMID- 9649571
TI  - Estrogen upregulates cyclooxygenase-1 gene expression in ovine fetal pulmonary
      artery endothelium.
AB  - Prostacyclin (PGI2) is a key mediator of pulmonary vasodilation in the perinatal
      period and its synthesis in the pulmonary vasculature increases markedly during
      late gestation due to enhanced expression of the rate-limiting enzyme
      cyclooxygenase-1 (COX-1). The hormone estrogen may play a role in COX-1
      upregulation since fetal estrogen levels rise dramatically during late gestation
      and estrogen enhances PGI2 synthesis in nonpulmonary vascular cells. We therefore
      studied the direct effects of estrogen on COX-1 expression in ovine fetal
      pulmonary artery endothelial cells (PAEC). Exposure to estradiol-17beta (E2beta,
      10(-)10 to 10(-)6 M) caused a dose-related increase in COX-1 mRNA expression that
      was evident after 48 h and maximal at 10(-)8 M (fourfold increase). COX-1 mRNA
      stability was unchanged, suggesting that the upregulation is mediated at the
      level of transcription. E2beta treatment (10(-)8 M for 48 h) also caused a
      threefold increase in COX-1 protein expression and a threefold increase in PGI2
      synthesis stimulated by bradykinin, the calcium ionophore A23187, or arachidonic
      acid. The estrogen receptor (ER) antagonist ICI 182,780 fully reversed the
      effects of the hormone on COX-1 protein expression and on arachidonic acid
      stimulated PGI2 synthesis, and ER expression was evident in the PAEC by
      immunoblot analysis. These findings indicate that physiologic levels of estrogen
      cause upregulation of COX-1 expression and PGI2 synthesis in fetal PAEC via
      activation of PAEC ER. This process may play a critical role in optimizing the
      capacity for PGI2-mediated pulmonary vasodilation at birth, and it may also be
      involved in estrogen responsiveness in other vascular beds.

PMID- 9649572
TI  - Incorporation of adenovirus in calcium phosphate precipitates enhances gene
      transfer to airway epithelia in vitro and in vivo.
AB  - Adenovirus (Ad)-mediated gene transfer to airway epithelia is inefficient because
      the apical membrane lacks the receptor activity to bind adenovirus fiber protein.
      Calcium phosphate (CaPi) precipitates have been used to deliver plasmid DNA to
      cultured cell lines. However, such precipitates are not effective in many primary
      cultures or in vivo. Here we show that incorporating recombinant adenovirus into
      a CaPi coprecipitate markedly enhances transgene expression in cells that are
      resistant to adenovirus infection. Enhancement requires that the virus be
      contained in the precipitate and viral proteins are required to increase
      expression. Ad: CaPi coprecipitates increase gene transfer by increasing fiber
      independent binding of virus to cells. With differentiated cystic fibrosis (CF)
      airway epithelia in vitro, a 20-min application of Ad:CaPi coprecipitates that
      encode CF transmembrane conductance regulator produced as much CF transmembrane
      conductance regulator Cl- current as a 24-h application of adenovirus alone. We
      found that Ad:CaPi coprecipitates also increased transgene expression in mouse
      lung in vivo; importantly, expression was particularly prominent in airway
      epithelia. These results suggest a new mechanism for gene transfer that may be
      applicable to a number of different gene transfer applications and could be of
      value in gene transfer to CF airway epithelia in vivo.

PMID- 9649573
TI  - Prostaglandin E2 inhibits renal collecting duct Na+ absorption by activating the
      EP1 receptor.
AB  - PGE2 exerts potent diuretic and natriuretic effects on the kidney. This action is
      mediated in part by direct inhibition of collecting duct Na+ absorption via a
      Ca++-coupled mechanism. These studies examine the role the Ca++-coupled PGE-E EP1
      receptor plays in mediating these effects of PGE2 on Na+ transport. Rabbit EP1
      receptor cDNA was amplified from rabbit kidney RNA. Nuclease protection assays
      demonstrated highest expression of EP1 mRNA in kidney, followed by stomach,
      adrenal, and ileum. In situ hybridization, demonstrated renal expression of EP1
      mRNA was exclusively over the collecting duct. In fura-2-loaded microperfused
      rabbit cortical collecting duct, EP1 active PGE analogs were 10-1, 000-fold more
      potent in raising intracellular Ca++ than EP2, EP3, or EP4-selective compounds.
      Two different EP1 antagonists, AH6809 and SC19220, completely blocked the PGE2
      stimulated intracellular calcium increase. AH6809 also completely blocked the
      inhibitory effect of PGE2 on Na+ absorption in microperfused rabbit cortical
      collecting ducts. These studies suggest that EP1 receptor activation mediates
      PGE2-dependent inhibition of Na+ absorption in the collecting duct, thereby
      contributing to its natriuretic effects.

PMID- 9649574
TI  - Osteogenic protein-1 (bone morphogenetic protein-7) reduces severity of injury
      after ischemic acute renal failure in rat.
AB  - We have shown that osteogenic protein-1 (OP-1) (bone morphogenetic protein-7) is
      responsible for the induction of nephrogenic mesenchyme during embryonic kidney
      development. Gene knock-out studies showed that OP-1 null mutant mice die of
      renal failure within the first day of postnatal life. In the present study, we
      evaluated the effect of recombinant human OP-1 for the treatment of acute renal
      failure after 60 min bilateral renal artery occlusion in rats. Bioavailability
      studies in normal rats indicate that approximately 1.4 microg OP-1/ml is
      available in the circulation 1 min after intravenous administration of 250
      microg/kg, which then declines steadily with a half life of 30 min. About 0.5% of
      the administered OP-1 dose/g tissue is targeted for OP-1 receptors in the kidney.
      We show that OP-1 preserves kidney function, as determined by reduced blood urea
      nitrogen and serum creatinine, and increased survival rate when administered 10
      min before or 1 or 16 h after ischemia, and then at 24-h intervals up to 72 h
      after reperfusion. Histochemical and molecular analyses demonstrate that OP-1:
      (a) minimizes infarction and cell necrosis, and decreases the number of plugged
      tubules; (b) suppresses inflammation by downregulating the expression of
      intercellular adhesive molecule, and prevents the accumulation and activity of
      neutrophils; (c) maintains the expression of the vascular smooth muscle cell
      phenotype in pericellular capillaries; and (d) reduces programmed cell death
      during the recovery. Collectively, these data suggest that OP-1 prevents the loss
      of kidney function associated with ischemic injury and may provide a basis for
      the treatment of acute renal failure.

PMID- 9649575
TI  - Anti-idiotypic antibodies prevent the serologic detection of antiribosomal P
      autoantibodies in healthy adults.
AB  - A subset of SLE patients has serologically detectable autoantibodies to the
      ribosomal P proteins (anti-P). We reported the discovery of covert anti-P
      antibodies and their masking IgG-inhibitory antibodies in the sera of healthy
      adults. The aim of this study was to determine if these IgG-inhibitory antibodies
      are anti-idiotypic antibodies (anti-Ids). IgG and IgG-depleted fractions of
      plasma from two healthy adults were assayed for inhibition of anti-P F(ab')2
      binding to the ribosomal P proteins in immunoblot. Anti-P antibody activity was
      completely inhibited by plasma IgG, whereas there was no inhibition by IgG
      depleted plasma. IgG-inhibitory antibodies recognized a cross-reactive epitope
      among anti-P from different SLE patients. Plasma IgG from one healthy adult was
      depleted of pepsin agglutinators and generic anti-F(ab')2 antibodies by
      adsorption with an affinity column prepared with normal IgG F(ab')2. Unretained
      IgG bound exclusively to anti-P F(ab')2 in ELISA. Using four affinity columns, we
      isolated IgG anti-Ids to anti-P antibodies from four healthy adults. These
      purified anti-Ids bound to anti-P F(ab')2 from a healthy adult and SLE patients.
      They did not bind to F(ab')2 fragments prepared from normal IgG or anti-dsDNA.
      Ribosomal antigens blocked this anti-Id-Id interaction. Purified anti-Ids
      inhibited the binding of anti-P F(ab')2 from patients to ribosomal P proteins.
      SLE patients without overt anti-P antibodies also possessed IgG anti-Ids to anti
      P antibodies. We conclude that IgG-inhibitory antibodies are anti-Ids to anti-P
      antibodies, and are directed to public idiotopes on anti-P antibodies. These anti
      Ids may be part of an Id network that regulates anti-P antibody expression, and
      perhaps pathogenicity.

PMID- 9649576
TI  - Natural killer cells from human immunodeficiency virus (HIV)-infected individuals
      are an important source of CC-chemokines and suppress HIV-1 entry and replication
      in vitro.
AB  - Macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES (regulated on
      activation, normal T cell expressed and secreted), which are the natural ligands
      of the CC-chemokine receptor CCR5, inhibit replication of MT-2- negative strains
      of HIV-1 by interfering with the ability of these strains to utilize CCR5 as a
      coreceptor for entry in CD4(+) cells. The present study investigates the capacity
      of natural killer (NK) cells isolated from HIV-infected individuals to produce CC
      chemokines and to suppress HIV replication in autologous, endogenously infected
      cells as well as to block entry of MT-2-negative HIV into the CD4(+) T cell line
      PM-1. NK cells freshly isolated from HIV-infected individuals had a high number
      of mRNA copies for MIP-1alpha and RANTES. NK cells produced significant amounts
      of RANTES, MIP-1alpha, and MIP-1beta constitutively, in response to stimulation
      with IL-2 alone and when they were performing their characteristic lytic activity
      (K562 killing). After CD16 cross-linking and stimulation with IL-2 or IL-15 NK
      cells produced CC-chemokines to levels comparable to those produced by anti-CD3
      stimulated CD8(+) T cells. Furthermore, CD16 cross-linked NK cells suppressed (49
      97%) viral replication in cocultures of autologous CD8/NK-depleted PBMC to a
      degree similar to that of PHA or anti-CD3-stimulated CD8(+) T cells. In 50% of
      patients tested, NK-mediated HIV suppression could be abrogated by neutralizing
      antibodies to MIP-1alpha, MIP-1beta and RANTES; in contrast, CD8(+) T cell
      mediated suppression was not significantly overcome upon neutralization of CC
      chemokines. Supernatants derived from cultures of CD16 cross-linked NK cells
      stimulated with IL-2 or IL-15 dramatically inhibited entry of a MT-2-negative
      strain of HIV, BaL, in the CD4(+)CCR5(+) PM-1 T cell line. These data suggest
      that activated NK cells may be an important source of CC-chemokines in vivo and
      may suppress HIV replication by CC-chemokine-mediated mechanisms in addition to
      classic NK-mediated lytic mechanisms.

PMID- 9649577
TI  - Insulin promoter factor-1 gene mutation linked to early-onset type 2 diabetes
      mellitus directs expression of a dominant negative isoprotein.
AB  - The homeodomain transcription factor insulin promoter factor-1 (IPF-1) is
      required for development of the pancreas and also mediates glucose-responsive
      stimulation of insulin gene transcription. Earlier we described a human subject
      with pancreatic agenesis attributable to homozygosity for a cytosine deletion in
      codon 63 of the IPF-1 gene (Pro63fsdelC). Pro63fsdelC resulted in the premature
      truncation of an IPF-1 protein which lacked the homeodomain required for DNA
      binding and nuclear localization. Subsequently, we linked the heterozygous state
      of this mutation with type 2 diabetes mellitus in the extended family of the
      pancreatic agenesis proband. In the course of expressing the mutant IPF-1 protein
      in eukaryotic cells, we detected a second IPF-1 isoform, recognized by COOH- but
      not NH2-terminal-specific antisera. This isoform localizes to the nucleus and
      retains DNA-binding functions. We provide evidence that internal translation
      initiating at an out-of-frame AUG accounts for the appearance of this protein.
      The reading frame crosses over to the wild-type IPF-1 reading frame at the site
      of the point deletion just carboxy proximal to the transactivation domain. Thus,
      the single mutated allele results in the translation of two IPF-1 isoproteins,
      one of which consists of the NH2-terminal transactivation domain and is
      sequestered in the cytoplasm and the second of which contains the COOH-terminal
      DNA-binding domain, but lacks the transactivation domain. Further, the COOH
      terminal mutant IPF-1 isoform does not activate transcription and inhibits the
      transactivation functions of wild-type IPF-1. This circumstance suggests that the
      mechanism of diabetes in these individuals may be due not only to reduced gene
      dosage, but also to a dominant negative inhibition of transcription of the
      insulin gene and other beta cell-specific genes regulated by the mutant IPF-1.

PMID- 9649578
TI  - Virus- and interferon-induced loss of inhibitory M2 muscarinic receptor function
      and gene expression in cultured airway parasympathetic neurons.
AB  - Viral infections increase vagally mediated reflex bronchoconstriction. Decreased
      function of inhibitory M2 muscarinic receptors on the parasympathetic nerve
      endings is likely to contribute to increased acetylcholine release. In this
      study, we used cultured airway parasympathetic neurons to determine the effects
      of parainfluenza virus and of interferon (IFN)-gamma on acetylcholine release,
      inhibitory M2 receptor function, and M2 receptor gene expression. In control
      cultures, electrically stimulated acetylcholine release increased when the
      inhibitory M2 receptors were blocked using atropine (10(-)5 M) and decreased when
      these receptors were stimulated using methacholine (10(-)5 M). Acetylcholine
      release was increased by viral infection and by treatment with IFN-gamma (300
      U/ml). In these cells, atropine did not further potentiate, nor did methacholine
      inhibit, acetylcholine release, suggesting decreased inhibitory M2 receptor
      function and/or expression. Using a competitive reverse transcription-polymerase
      chain reaction method, we demonstrated that M2 receptor gene expression was
      decreased by more that an order of magnitude both by virus infection and by
      treatment with IFN. Thus, viral infections may increase vagally mediated
      bronchoconstriction both by directly inhibiting M2 receptor gene expression and
      by causing release of IFN-gamma which inhibits M2 receptor gene expression.

PMID- 9649579
TI  - Regulation of acetylcholine receptor gene expression in human myasthenia gravis
      muscles. Evidences for a compensatory mechanism triggered by receptor loss.
AB  - Myasthenia gravis (MG) is a neuromuscular disorder mediated by antibodies
      directed against the acetylcholine receptor (nAChR) resulting in a functional
      nAChR loss. To analyze the molecular mechanisms involved at the muscular target
      site, we studied the expression of nAChR subunits in muscle biopsy specimens from
      MG patients. By using quantitative PCR with an internal standard for each
      subunit, we found that the levels of beta-, delta-, and epsilon-subunit mRNA
      coding for the adult nAChR were increased in severely affected MG patients,
      matching our previous data on the alpha-subunit. Messenger levels were highly
      variable in MG patients but not in controls, pointing to individual factors
      involved in the regulation of nAChR genes. The fetal subunit (gamma-chain)
      transcripts were almost undetectable in the extrajunctional region of MG muscle,
      suggesting that gene regulation in MG differs from that in the denervation model,
      in which nAChR gamma-subunit mRNA is reexpressed. Nicotinic AChR loss mediated by
      monoclonal anti-nAChR antibodies in both the TE671 muscle cell line and cultured
      normal human myotubes induces a similar increase in beta- alphand delta-subunit
      mRNA levels, suggesting the existence of a new muscular signaling pathway system
      coupled to nAChR internalization and independent of muscle electrical activity.
      These data demonstrate the existence of a compensatory mechanism regulating the
      expression of the genes coding for the adult nAChR in patients with MG.

PMID- 9649580
TI  - The voltage dependence of a cloned mammalian renal type II Na+/Pi cotransporter
      (NaPi-2).
AB  - The voltage dependence of the rat renal type II Na+/Pi cotransporter (NaPi-2) was
      investigated by expressing NaPi-2 in Xenopus laevis oocytes and applying the two
      electrode voltage clamp. In the steady state, superfusion with inorganic
      phosphate (Pi) induced inward currents (Ip) in the presence of 96 mM Na+ over the
      potential range -140 </= V </= +40 mV. With Pi as the variable substrate, the
      apparent affinity constant (KmPi) was strongly dependent on Na+, increasing
      sixfold for a twofold reduction in external Na+. KmPi increased with depolarizing
      voltage and was more sensitive to voltage at reduced Na+. The Hill coefficient
      was close to unity and the predicted maximum Ip (Ipmax) was 40% smaller at 50 mM
      Na+. With Na+ as the variable substrate, KmNa was weakly dependent on both Pi and
      voltage, the Hill coefficient was close to 3 and Ipmax was independent of Pi at 
      50 mV. The competitive inhibitor phosphonoformic acid suppressed the steady state
      holding current in a Na+-dependent manner, indicating the existence of uncoupled
      Na+ slippage. Voltage steps induced pre-steady state relaxations typical for Na+
      coupled cotransporters. NaPi-2-dependent relaxations were quantitated by a
      single, voltage-dependent exponential. At 96 mM Na+, a Boltzmann function was fit
      to the steady state charge distribution (Q-V) to give a midpoint voltage (V0.5)
      in the range -20 to -50 mV and an apparent valency of approximately 0.5 e-. V0.5
      became more negative as Na+ was reduced. Pi suppressed relaxations in a dose
      dependent manner, but had little effect on their voltage dependence. Reducing
      external pH shifted V0.5 to depolarizing potentials and suppressed relaxations in
      the absence of Na+, suggesting that protons interact with the unloaded carrier.
      These findings were incorporated into an ordered kinetic model whereby Na+ is the
      first and last substrate to bind, and the observed voltage dependence arises from
      the unloaded carrier and first Na+ binding step.

PMID- 9649581
TI  - Patch clamp on the luminal membrane of exocrine gland acini from frog skin (Rana
      esculenta) reveals the presence of cystic fibrosis transmembrane conductance
      regulator-like Cl- channels activated by cyclic AMP.
AB  - Chloride channels in the luminal membrane of exocrine gland acini from frog skin
      (Rana esculenta) constituted a single homogeneous population. In cell-attached
      patches, channels activated upon exposure to isoproterenol, forskolin, or
      dibutyryl-cAMP and isobutyl-1-methyl-xanthine rectified in the outward direction
      with a conductance of 10.0 +/- 0.4 pS for outgoing currents. Channels in
      stimulated cells reversed at 0 mV applied potential, whereas channels in
      unstimulated cells reversed at depolarized potentials (28.1 +/- 6.7 mV),
      indicating that Cl- was above electrochemical equilibrium in unstimulated, but
      not in stimulated, cells. In excised inside-out patches with 25 mM Cl- on the
      inside, activity of small (8-pS) linear Cl--selective channels was dependent upon
      bath ATP (1.5 mM) and increased upon exposure to cAMP-dependent protein kinase.
      The channels displayed a single substate, located just below 2/3 of the full
      channel amplitude. Halide selectivity was identified as PBr > PI > PCl from the
      Goldman equation; however, the conductance sequence when either halide was
      permeating the channel was GCl > GBr >> GI. In inside-out patches, the channels
      were blocked reversibly by 5-nitro-2-(3-phenylpropylamino)benzoic acid,
      glibenclamide, and diphenylamine-2-carboxylic acid, whereas 4, 4
      diisothiocyanatostilbene-2,2-disulfonic acid blocked channel activity completely
      and irreversibly. Single-channel kinetics revealed one open state (mean lifetime
      = 158 +/- 72 ms) and two closed states (lifetimes: 12 +/- 4 and 224 +/- 31 ms,
      respectively). Power density spectra had a double-Lorentzian form with corner
      frequencies 0.85 +/- 0.11 and 27.9 +/- 2.9 Hz, respectively. These channels are
      considered homologous to the cystic fibrosis transmembrane conductance regulator
      Cl- channel, which has been localized to the submucosal skin glands in Xenopus by
      immunohistochemistry (Engelhardt, J.F., S.S. Smith, E. Allen, J.R. Yankaskas,
      D.C. Dawson, and J.M. Wilson. 1994. Am. J. Physiol. 267: C491-C500) and, when
      stimulated by cAMP-dependent phosphorylation, are suggested to function in
      chloride secretion.

PMID- 9649582
TI  - Properties of a novel pH-dependent Ca2+ permeation pathway present in male germ
      cells with possible roles in spermatogenesis and mature sperm function.
AB  - Rises of intracellular Ca2+ ([Ca2+]i) are key signals for cell division,
      differentiation, and maturation. Similarly, they are likely to be important for
      the unique processes of meiosis and spermatogenesis, carried out exclusively by
      male germ cells. In addition, elevations of [Ca2+]i and intracellular pH (pHi) in
      mature sperm trigger at least two events obligatory for fertilization:
      capacitation and acrosome reaction. Evidence implicates the activity of Ca2+
      channels modulated by pHi in the origin of these Ca2+ elevations, but their
      nature remains unexplored, in part because work in individual spermatozoa are
      hampered by formidable experimental difficulties. Recently, late spermatogenic
      cells have emerged as a model system for studying aspects relevant for sperm
      physiology, such as plasmalemmal ion fluxes. Here we describe the first study on
      the influence of controlled intracellular alkalinization on [Ca2+]i on identified
      spermatogenic cells from mouse adult testes. In BCECF [(2',7')-bis(carboxymethyl)
      (5, 6)-carboxyfluorescein]-AM-loaded spermatogenic cells, a brief (30-60 s)
      application of 25 mM NH4Cl increased pHi by approximately 1.3 U from a resting
      pHi approximately 6.65. A steady pHi plateau was maintained during NH4Cl
      application, with little or no rebound acidification. In fura-2-AM-loaded cells,
      alkalinization induced a biphasic response composed of an initial [Ca2+]i drop
      followed by a two- to threefold rise. Maneuvers that inhibit either Ca2+ influx
      or intracellular Ca2+ release demonstrated that the majority of the Ca2+ rise
      results from plasma membrane Ca2+ influx, although a small component likely to
      result from intracellular Ca2+ release was occasionally observed. Ca2+ transients
      potentiated with repeated NH4Cl applications, gradually obliterating the initial
      [Ca2+]i drop. The pH-sensitive Ca2+ permeation pathway allows the passage of
      other divalents (Sr2+, Ba2+, and Mn2+) and is blocked by inorganic Ca2+ channel
      blockers (Ni2+ and Cd2+), but not by the organic blocker nifedipine. The
      magnitude of these Ca2+ transients increased as maturation advanced, with the
      largest responses being recorded in testicular sperm. By extrapolation, these
      findings suggest that the pH-dependent Ca2+ influx pathway could play significant
      roles in mature sperm physiology. Its pharmacology and ion selectivity suggests
      that it corresponds to an ion channel different from the voltage-gated T-type
      Ca2+ channel also present in spermatogenic cells. We postulate that the Ca2+
      permeation pathway regulated by pHi, if present in mature sperm, may be
      responsible for the dihydropyridine-insensitive Ca2+ influx required for
      initiating the acrosome reaction and perhaps other important sperm functions.

PMID- 9649583
TI  - Interactions of a reversible ryanoid (21-amino-9alpha-hydroxy-ryanodine) with
      single sheep cardiac ryanodine receptor channels.
AB  - The binding of ryanodine to a high affinity site on the sarcoplasmic reticulum
      Ca2+-release channel results in a dramatic alteration in both gating and ion
      handling; the channel enters a high open probability, reduced-conductance state.
      Once bound, ryanodine does not dissociate from its site within the time frame of
      a single channel experiment. In this report, we describe the interactions of a
      synthetic ryanoid, 21-amino-9alpha-hydroxy-ryanodine, with the high affinity
      ryanodine binding site on the sheep cardiac sarcoplasmic reticulum Ca2+-release
      channel. The interaction of 21-amino-9alpha-hydroxy-ryanodine with the channel
      induces the occurrence of a characteristic high open probability, reduced
      conductance state; however, in contrast to ryanodine, the interaction of this
      ryanoid with the channel is reversible under steady state conditions, with dwell
      times in the modified state lasting seconds. By monitoring the reversible
      interaction of this ryanoid with single channels under voltage clamp conditions,
      we have established a number of novel features of the ryanoid binding reaction.
      (a) Modification of channel function occurs when a single molecule of ryanoid
      binds to the channel protein. (b) The ryanoid has access to its binding site only
      from the cytosolic side of the channel and the site is available only when the
      channel is open. (c) The interaction of 21-amino-9alpha-hydroxy-ryanodine with
      its binding site is influenced strongly by transmembrane voltage. We suggest that
      this voltage dependence is derived from a voltage-driven conformational
      alteration of the channel protein that changes the affinity of the binding site,
      rather than the translocation of the ryanoid into the voltage drop across the
      channel.

PMID- 9649584
TI  - Interactions between multiple phosphorylation sites in the inactivation particle
      of a K+ channel. Insights into the molecular mechanism of protein kinase C
      action.
AB  - Protein kinase C inhibits inactivation gating of Kv3.4 K+ channels, and at least
      two NH2-terminal serines (S15 and S21) appeared involved in this interaction (.
      Neuron. 13:1403-1412). Here we have investigated the molecular mechanism of this
      regulatory process. Site-directed mutagenesis (serine --> alanine) revealed two
      additional sites at S8 and S9. The mutation S9A inhibited the action of PKC by
      approximately 85%, whereas S8A, S15A, and S21A exhibited smaller reductions (41,
      35, and 50%, respectively). In spite of the relatively large effects of
      individual S --> A mutations, simultaneous mutation of the four sites was
      necessary to completely abolish inhibition of inactivation by PKC. Accordingly, a
      peptide corresponding to the inactivation domain of Kv3.4 was phosphorylated by
      specific PKC isoforms, but the mutant peptide (S[8,9,15,21]A) was not.
      Substitutions of negatively charged aspartate (D) for serine at positions 8, 9,
      15, and 21 closely mimicked the effect of phosphorylation on channel
      inactivation. S --> D mutations slowed the rate of inactivation and accelerated
      the rate of recovery from inactivation. Thus, the negative charge of the
      phosphoserines is an important incentive to inhibit inactivation. Consistent with
      this interpretation, the effects of S8D and S8E (E = Glu) were very similar, yet
      S8N (N = Asn) had little effect on the onset of inactivation but accelerated the
      recovery from inactivation. Interestingly, the effects of single S --> D
      mutations were unequal and the effects of combined mutations were greater than
      expected assuming a simple additive effect of the free energies that the single
      mutations contribute to impair inactivation. These observations demonstrate that
      the inactivation particle of Kv3.4 does not behave as a point charge and suggest
      that the NH2-terminal phosphoserines interact in a cooperative manner to disrupt
      inactivation. Inspection of the tertiary structure of the inactivation domain of
      Kv3.4 revealed the topography of the phosphorylation sites and possible
      interactions that can explain the action of PKC on inactivation gating.

PMID- 9649585
TI  - Macroscopic Na+ currents in the "Nonconducting" Shaker potassium channel mutant
      W434F.
AB  - C-type inactivation in Shaker potassium channels inhibits K+ permeation. The
      associated structural changes appear to involve the outer region of the pore.
      Recently, we have shown that C-type inactivation involves a change in the
      selectivity of the Shaker channel, such that C-type inactivated channels show
      maintained voltage-sensitive activation and deactivation of Na+ and Li+ currents
      in K+-free solutions, although they show no measurable ionic currents in
      physiological solutions. In addition, it appears that the effective block of ion
      conduction produced by the mutation W434F in the pore region may be associated
      with permanent C-type inactivation of W434F channels. These conclusions predict
      that permanently C-type inactivated W434F channels would also show Na+ and Li+
      currents (in K+-free solutions) with kinetics similar to those seen in C-type
      inactivated Shaker channels. This paper confirms that prediction and demonstrates
      that activation and deactivation parameters for this mutant can be obtained from
      macroscopic ionic current measurements. We also show that the prolonged Na+ tail
      currents typical of C-type inactivated channels involve an equivalent
      prolongation of the return of gating charge, thus demonstrating that the kinetics
      of gating charge return in W434F channels can be markedly altered by changes in
      ionic conditions.

PMID- 9649586
TI  - Vitamin A is required for regulation of polymeric immunoglobulin receptor (pIgR)
      expression by interleukin-4 and interferon-gamma in a human intestinal epithelial
      cell line.
AB  - The secretory immunoglobulin A (IgA) antibody response to infections of mucosal
      surfaces requires transport of IgA from the basal to apical surface of mucosal
      epithelial cells by a specific transport protein, the polymeric immunoglobulin
      receptor (pIgR). We have tested the hypothesis that the vitamin A metabolite all
      trans retinoic acid (RA) is required for the regulation of pIgR expression by the
      cytokines interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) in HT-29 cells, a
      well-differentiated human epithelial cell line derived from a colonic carcinoma.
      pIgR expression is upregulated by IFN-gamma and IL-4 when HT-29 cells are grown
      in normal media, but this upregulation was significantly lower when cells were
      grown in vitamin A-depleted media. Treatment with RA at concentrations from 10(
      9) to 10(-5) mol/L restored normal levels of pIgR expression. The percentages of
      cells expressing cell-surface pIgR after 24, 48 and 72 h of treatment with RA, IL
      4 and IFN-gamma were 66 +/- 10, 90 +/- 5 and 92 +/- 1, respectively,
      significantly higher than the percentages seen without RA treatment, which were
      32 +/- 2.3, 72 +/- 1.2 and 30 +/- 7, respectively. In addition, the intensity of
      fluorescence of pIgR-positive cells was significantly higher in the RA-treated
      cultures than in the cultures without RA treatment. Similarly, pIgR mRNA levels
      (adjusted for beta-actin mRNA levels) in RA-supplemented cultures were 404, 105
      and 949% higher at 24, 48 and 72 h, respectively, than were pIgR mRNA levels in
      identical cultures grown in the absence of RA. These data indicate that RA
      strongly interacts with IL-4 and IFN-gamma to regulate pIgR expression in HT-29
      cells, suggesting that vitamin A may be required for proper in vivo regulation of
      IgA transport in response to mucosal infections.

PMID- 9649587
TI  - Cellular glutathione peroxidase is the mediator of body selenium to protect
      against paraquat lethality in transgenic mice.
AB  - The antioxidative role of Se-dependent cellular glutathione peroxidase (EC
      1.11.1.9, GPX1) in vivo has not been established. Our objective was to determine
      the effects of GPX1 knockout or overexpression on the susceptibility of mice to
      paraquat toxicity and the contributions of GPX1, compared with other
      selenoproteins and vitamin E, to body defenses against such acute oxidative
      stress. Four experiments were conducted using 111 GPX1 knockout or overexpressing
      mice and the respective controls. Mice were fed diets supplemented with Se (as
      sodium selenite) at 0-0.4 mg/kg and/or all-rac-alpha-tocopheryl acetate at 0-75
      mg/kg before intraperitoneal injections of 12.5, 50 or 125 mg paraquat/kg body
      weight. All mice that received 50 or 125 mg paraquat/kg died spontaneously, and
      the survival time of mice was (independent of dietary levels of Se per se or
      alpha-tocopheryl acetate) solely a function of tissue GPX1 activity (P < 0.001).
      Severe acute pulmonary interstitial necrosis was found only in the GPX1
      overexpressing mice and the controls that had extended survival time.
      Thiobarbituric acid reacting substances in postmortem liver inversely correlated
      with the tissue GPX1 activity and dietary levels of Se and/or alpha-tocopheryl
      acetate. In contrast, all mice that received 12.5 mg paraquat/kg survived and
      were killed 2 wk after the injection for tissue collection. Compared with the
      saline injection, this low dose of paraquat resulted in greater (P < 0.001) liver
      and lung F2-isoprostanes in both the GPX1 knockout mice and the controls.
      However, there was no difference in plasma alanine transaminase (EC 2.6.1.2)
      activity or overt injuries in liver, lung and kidney in either group. Our data
      indicate that GPX1 is the major, if not the only, metabolic form of body Se that
      protects mice against the lethal oxidative stress caused by high levels of
      paraquat; it seems less important, however, in protecting mice against the
      moderate oxidative stress by the low level of paraquat.

PMID- 9649588
TI  - Iron deficiency reduces the hydrolysis of cell membrane phosphatidyl inositol-4,5
      bisphosphate during splenic lymphocyte activation in C57BL/6 mice.
AB  - Iron deficiency impairs lymphocyte proliferation in humans and laboratory animals
      by unknown mechanisms. In this study, we investigated whether this alteration can
      be attributed in part to impaired hydrolysis of cell membrane phosphatidyl
      inositol-4, 5-bisphosphate (PIP2), a required early event of T-lymphocyte
      activation. The study involved 46 iron-deficient (ID), 26 control (C) and 23 pair
      fed (PF) mice, and ID mice that were repleted for 3 (n = 16), 7 (n = 17) or 14 d
      (n = 18). Mice were killed after 40-63 d (mean, 48 d) of consuming the test diet
      (0.09 mmol/kg iron) or the control diet (0.9 mmol/kg). The mean (+/-SEM)
      hemoglobin concentrations were 57 +/- 16.7, 176 +/- 2.6 and 181 +/- 9.7 g/L for
      ID, C and PF groups, respectively. After splenic lymphocytes were labeled in
      vitro with 3H-myoinositol for 3 h, PIP2 hydrolysis was estimated by measuring the
      radioactivity recovered as a mixture of inositol mono-, di- and triphosphate (IP)
      from concanavalin A (0, 1, 2.5, 5 and 10 mg/L) activated cells. Although cells
      from ID mice and those from mice repleted for 3 d incorporated slightly more
      radioactivity in cellular phospholipids than did cells from C or PF mice, less (P
      < 0.005) was recovered as IP than in controls, suggesting impaired conversion of
      the precursor to PIP2. At almost all incubation periods (10-120 min) and mitogen
      concentrations, the rate of PIP2 hydrolysis expressed as the ratio of
      radioactivity obtained in Con A-treated to untreated cells was significantly (P <
      0.05) reduced in cells from ID mice compared with those obtained from C and PF
      mice. For cells that were activated for 60 min or less, iron repletion for 14 d
      significantly (P < 0.05) improved the rate of PIP2 hydrolysis. PIP2 hydrolysis
      positively and significantly (P < 0.05) correlated (r = 0.27-0.56) with
      indicators of iron status. Mitogenic response was also significantly (P < 0.05)
      reduced in ID but not PF mice, and it was corrected by iron repletion for 3, 7 or
      14 d. Lymphocyte proliferation positively (r = 0.27-0.37, P < 0.01) correlated
      with indices of iron status and IP ratios. The data suggest that reduced PIP2
      hydrolysis contributes to impaired blastogenesis in iron deficiency.

PMID- 9649589
TI  - Highly purified soybean protein is not hypocholesterolemic in rats but stimulates
      cholesterol synthesis and excretion and reduces polyunsaturated fatty acid
      biosynthesis.
AB  - The specific effects of soybean protein on lipid metabolism were determined with
      highly purified soybean protein. At 5 wk of age, growing rats were fed diets
      containing 20% highly purified soybean protein or casein supplemented or not with
      0.1% cholesterol for 2 mo. Plasma and liver lipid composition, fecal steroid
      excretion and several hepatic enzyme activities were measured. There were no
      significant dietary protein-related differences in plasma and liver cholesterol
      concentrations. When diets were cholesterol free, highly purified soybean protein
      stimulated fecal neutral and acidic steroid excretion associated with
      concomitantly higher hydroxy methylglutaryl CoA (HMG-CoA) reductase activity, but
      lower cholesterol 7alpha-hydroxylase activity. Soybean protein lowered the
      linoleate desaturation index [20:4(n-6)/18:2(n-6)] in liver microsomal lipids and
      phospholipids. This may have been due to the reduced microsomal Delta6(n-6)
      desaturase activity in rats fed soybean protein, whereas Delta5(n-6) desaturase
      activity did not differ between groups fed the two proteins. Cholesterol
      supplementation (0.1%) did not affect plasma cholesterol but increased liver
      cholesterol and triacylglycerol concentrations and reduced HMG-CoA reductase
      activity; this latter effect was greatest in rats fed soybean protein.
      Cholesterol 7alpha-hydroxylase activity, however, was diminished only in rats fed
      casein. Desaturase activities, and particularly Delta5(n-6) activity, were
      lowered by cholesterol supplementation in rats fed both protein diets, including
      a significantly lower 20:4(n-6)/18:2(n-6) ratio in liver microsomal lipids and
      liver phospholipids. Thus although dietary proteins have no effect on serum
      cholesterol in rats, they affect enzyme activities involved in cholesterol
      metabolism and fatty acid desaturation.

PMID- 9649590
TI  - Zinc deficiency enhances interleukin-1alpha-induced metallothionein-1 expression
      in rats.
AB  - This study investigated whether interleukin-1alpha-induced metallothionein gene
      expression is affected by zinc deficiency. Weaning male rats were fed a zinc
      deficient (ZD) diet (2 mg zinc/kg) or a zinc-supplemented diet [50.8 mg zinc/kg;
      controls for the diet included pair-fed (PF) and ad libitum consumption groups
      (AL)] for 4 wk. All rats except those that served as controls for interleukin
      1alpha administration, (injected with vehicle and killed at 0 h) were then
      injected subcutaneously with interleukin-1alpha (2 x 10(7) units/kg body wt) and
      killed at 3, 6, 12, 24 and 72 h after the injection. Compared with AL and/or PF
      rats, zinc depletion significantly reduced zinc concentrations in plasma and
      liver but not in kidney or intestine, and significantly reduced hepatic, renal,
      and intestinal metallothionein-1 mRNA levels analyzed by competitive reverse
      transcription-polymerase chain reaction (RT-PCR). Interleukin-1alpha injection
      reduced plasma zinc concentration and enhanced liver zinc concentration, but did
      not affect zinc levels in kidney or intestine. Metallothionein-1 mRNA was
      significantly elevated by interleukin-1alpha in liver, kidney and intestine of
      all groups; the levels in liver and kidney of ZD rats 6 h after the injection
      were significantly higher than those of AL or PF rats. Liver metallothionein
      protein levels were enhanced after interleukin-1alpha injection in both AL and ZD
      rats. Semiquantitative RT-PCR revealed significantly higher hepatic levels of
      interleukin-1 receptor type-I mRNA in ZD rats than in AL and PF rats but no
      differences in renal or intestinal tissues among groups before interleukin-1alpha
      challenge. In conclusion, zinc deficiency induces upregulation of metallothionein
      1 gene expression in response to interleukin-1alpha challenge in rats.

PMID- 9649591
TI  - Insulin, glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide
      and insulin-like growth factor I as putative mediators of the hypolipidemic
      effect of oligofructose in rats.
AB  - The addition of oligofructose as a dietary fiber decreases the serum
      concentration and the hepatic release of VLDL-triglycerides in rats. Because
      glucose, insulin, insulin-like growth factor I (IGF-I) and gut peptides [i.e.,
      glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1
      (GLP-1)]) are factors involved in the metabolic response to nutrients, this paper
      analyzes their putative role in the hypolipidemic effect of oligofructose. Male
      Wistar rats were fed a nonpurified diet with or without 10% oligofructose for 30
      d. Glucose, insulin, IGF-I and GIP concentrations were measured in the serum of
      rats after eating. GIP and GLP-1 contents were also assayed in small intestine
      and cecal extracts, respectively. A glucose tolerance test was performed in food
      deprived rats. Serum insulin level was significantly lower in oligofructose-fed
      rats both after eating and in the glucose tolerance test, whereas glycemia was
      lower only in the postprandial state. IGF-I serum level did not differ between
      groups. GIP concentration was significantly higher in the serum of oligofructose
      fed rats. The GLP-1 cecal pool was also significantly higher. In this study, we
      have shown that cecal proliferation induced by oligofructose leads to an increase
      in GLP-1 concentration. This latter incretin could be involved in the maintenance
      of glycemia despite a lower insulinemia in the glucose tolerance test in
      oligofructose-fed rats. We discuss also the role of hormonal changes in the
      antilipogenic effect of oligofructose.

PMID- 9649592
TI  - Dietary cholesterol affects serum lipids, lipoproteins and LDL metabolism in
      cynomolgus monkeys in a dose-dependent manner.
AB  - To examine the mechanism(s) underlying the cholesterolemic response to dietary
      cholesterol and saturated fatty acids, low density lipoprotein (LDL) metabolism
      was studied in two groups of cynomolgus monkeys fed diets containing 30 or 36% of
      total energy as fat. At each dietary fat level, the same group of monkeys was
      sequentially fed three dietary cholesterol concentrations as egg yolk in the
      following sequence: low (0.01 mg/kJ), medium (0.03 mg/kJ) and high (0.05 mg/kJ)
      for 30, 32 and 24 wk, respectively. Dietary polyunsaturated and monounsaturated
      fatty acids were the same in the two groups; the 6% difference in fat was due to
      the saturated fatty acids, 12:0 and 14:0. Serum total cholesterol, LDL
      cholesterol and LDL apolipoprotein B concentrations increased (P < 0.05) with
      dietary cholesterol in a dose-dependent manner in both fat groups. These
      elevations were the result of generally increasing LDL apolipoprotein B
      production rates, concomitant with reduced LDL apolipoprotein B fractional
      clearance at the high cholesterol intake. Serum HDL cholesterol and HDL
      apolipoprotein A-I concentrations were not affected in a consistent manner. These
      results demonstrate that cynomolgus monkeys are hyperresponsive to dietary
      cholesterol compared with humans, suggesting that this model may be useful in
      identifying metabolic and genetic predictors for hyperresponsiveness to dietary
      cholesterol in humans as well as assessing the metabolic heterogeneity of
      responses to dietary cholesterol.

PMID- 9649593
TI  - Food deprivation changes peroxisomal beta-oxidation activity but not catalase
      activity during postnatal development in pig tissues.
AB  - Peroxisomal beta-oxidation and catalase activity were investigated in liver,
      kidney and heart from pigs at the following timepoints: within 0.5 h after birth
      (0 h, unfed) and at 24 h (suckled or unsuckled), 10 d (suckled or 24-h food
      deprived), 21 d (suckled or 24-h food-deprived) and 5 mo (overnight food
      deprived). In liver, peroxisomal beta-oxidation increased about twofold at 24 h
      for suckled pigs (P < 0.001) but did not change for unsuckled pigs. The rate was
      further increased in 21-d-old pigs compared with 0- (P < 0. 001) or 24-h-old (P <
      0.05) pigs, but was lower at 5 mo than at 10 or 21 d (P < 0.01). The rate was
      higher for food-deprived pigs than suckled pigs at 10 d (P < 0.001) of age. In
      kidney, peroxisomal beta-oxidation was unchanged during the first 24 h but was
      higher (P < 0.05) at 10 d for suckled pigs and at 21 d than at 0 h. Nutritional
      state did not influence renal peroxisomal beta-oxidation. In heart, peroxisomal
      beta-oxidation did not change with age or nutritional state. The developmental
      pattern of fatty acyl-CoA oxidase activity was similar to that of peroxisomal
      beta-oxidation in each tissue. Developmental increases of peroxisomal beta
      oxidation were greater than those for first-cycle peroxisomal beta-oxidation
      reported earlier, suggesting that peroxisomal beta-oxidation became more complete
      in older pigs. Catalase activity did not change during the first 24 h after birth
      but then increased 10.5-, 2.9-fold and 33% at 10 d in liver, kidney and heart,
      respectively. The concentration of catalase mRNA was only 1.1- and 1. 3-fold
      higher at 10 d than at 24 h in liver and kidney, respectively. Catalase activity
      was not affected by food deprivation. We concluded the following: 1) peroxisomal
      beta-oxidation develops rapidly after birth and may be important for piglets to
      oxidize milk fatty acids; 2) food is required for the initial induction after
      birth; and 3) rapidly increased catalase activity during the first 10 d of life
      resulted from both pretranslational and post-translational regulation.

PMID- 9649594
TI  - Urinary iodine excretion is the most appropriate outcome indicator for iodine
      deficiency at field conditions at district level.
AB  - To empower local authorities to plan and evaluate adequate interventions,
      appropriate iodine deficiency disorders (IDD) indicators need to be identified.
      The aim of this study was to describe the magnitude and severity of IDD with
      different outcome indicators and associate them with functional indicators.
      Schoolchildren (n = 544) aged 8-10 y were assessed in 11 villages within five
      subdistricts of Malang District, East Java, Indonesia. Outcome indicators of IDD
      were goiter size as measured by palpation and ultrasonography (USG), urinary
      iodine excretion (UIE) and serum thyroid stimulating hormone (TSH) concentration
      in blood as well as functional indicators such as intellectual performance (IQ:
      Catell's Culture Fair Intelligence Test) and anthropometric indices. The total
      goiter rate (TGR) measured by palpation and USG were 35.7 and 54.4%,
      respectively. Based on UIE and TSH, the prevalence of iodine deficiency was 63.7
      and 3.4%, respectively. In individuals, goiter, thyroid volume and UIE were
      associated significantly (r = -0.35; P < 0.001 and r = -0.30; P = 0.02
      respectively). Among villages, TGR measured by palpation was significantly
      correlated with thyroid volume (r = 0.61; P = 0.045) and UIE (r = 0.68; P =
      0.021), whereas TSH was not significantly associated with any of the observed
      indicators in individuals or groups. Multiple regression analysis showed that USG
      (beta = -0.67; P < 0.001) and UIE (beta = 4.39; P = 0.008) related significantly
      with cognitive performance (IQ). The associations between IDD indicators and
      cognitive performance and height-for-age Z scores suggest that socioeconomically
      advantaged children had better iodine status. We suggest that UIE is the best
      indicator for local authorities to assess iodine deficiency.

PMID- 9649595
TI  - Eating from a shared plate affects food consumption in vitamin A-deficient Nepali
      children.
AB  - This case-control study evaluates the relationship between shared-plate eating
      behavior in young Nepali children (aged 1-6 y) and risk of vitamin A deficiency.
      Day-long observations of dietary practices were conducted on 7 d over a 15-mo
      period in 162 households: 81 households with a child with a known history of mild
      xerophthalmia (cases) were matched with 81 having a non-xerophthalmic child of
      similar age (controls). Shared-plate eating occurred in 25% of all feeding
      episodes and at least once in 65% of all days observed. Overall, children
      engaging in shared-plate eating were significantly more likely to consume grains,
      vegetables, carotenoid-rich vegetables, pulses, fruits, meats and fish, and dairy
      products and had significantly larger portion sizes for grains, vegetables,
      fruits, pulses and dairy products, compared with children who ate alone. In
      general, feeding behaviors between case and control children tended to be
      similar. However, shared-plate feeding episodes among case children were
      significantly less likely to include meats or fish [odds ratio (OR) = 0.5,
      confidence interval (CI) = 0.3-0.8], dairy products (OR = 0.6, CI = 0.4-0.9) or
      pulses (OR = 0.7, CI = 0.5-1.0). Individual-plate feeding episodes among case
      children were more likely to include vegetables (OR = 1.3, CI = 1.0-1.6) than
      those of control children. Case children were more likely to share a plate with a
      male adult (OR = 1.7, CI = 1.0-2.8), but less likely to eat from a plate shared
      with females of any age compared with controls (female adult: OR = 0.6, CI = 0.4
      0.9; female child: OR = 0.6, CI = 0.4-1.0). Shared-plate eating may benefit a
      young child's dietary intake, but the identity of the food sharer may modify this
      influence.

PMID- 9649596
TI  - The NCHS reference and the growth of breast- and bottle-fed infants.
AB  - The current international growth reference, the National Center for Health
      Statistics (NCHS) reference, is widely used to compare the nutritional status of
      populations and to assess the growth of individual children throughout the world.
      Recently, concerns were raised regarding the adequacy of this reference for
      assessing the growth of breast-fed infants. We used the NCHS reference to
      evaluate infant growth in one of the most developed areas of Brazil. Infants who
      were exclusively or predominantly breast-fed for the first 4-6 mo, and partially
      breast-fed thereafter, grew more rapidly than the NCHS reference in weight and
      length during the first 3 mo, but appeared to falter thereafter. The average
      growth of all infants, regardless of feeding pattern, was faster than the NCHS
      reference until approximately 6 mo, after which their growth became slower than
      that of the NCHS sample. To substantiate this finding, the NCHS growth curves
      were then compared with growth data of breast-fed infants in developed countries
      from pooled published studies, formula-fed North American and European infants
      and predominantly bottle-fed U.S. infants monitored by the Centers for Disease
      Control and Prevention (CDC) Pediatric Surveillance System. In all three cases,
      weights showed the same pattern as the Brazilian infants-higher than NCHS in the
      early months but an apparent decline thereafter. The pattern for length gain was
      similar but less marked. Breast-fed infants showed more pronounced declines than
      those who were predominantly bottle-fed. These findings suggest that the infancy
      portion of the NCHS reference does not adequately reflect the growth of either
      breast-fed or artificially fed infants. This probably results from
      characteristics of the original sample and from inadequate curve-fitting
      procedures. The development of an improved international growth reference that
      reflects the normal infant growth pattern is indicated.

PMID- 9649597
TI  - Sodium iron EDTA [NaFe(III)EDTA] as a food fortificant does not influence
      absorption and urinary excretion of manganese in healthy adults.
AB  - NaFe(III)EDTA is a promising iron (Fe) compound for food fortification programs
      because of its high Fe bioavailability from meals containing dietary inhibitors
      of Fe absorption such as phytic acid. However, this Fe compound is not currently
      used in any large-scale fortification program because of concern over its
      possible negative influence on the metabolism of other essential minerals or its
      possible influence on the absorption of potentially toxic elements, such as
      manganese (Mn). In this study, Mn absorption and urinary excretion were studied
      in adults after intake of an Fe-fortified weaning cereal labeled with 54Mn. In a
      crossover design, the fortification of the weaning cereal with Fe as NaFeEDTA was
      compared with ferrous sulfate. Manganese absorption was measured by extrapolation
      from whole-body retention data 10-30 d after intake, and urinary excretion of
      54Mn was measured over 7 d. No significant differences in 54Mn absorption or
      urinary excretion were found; 1.1 +/- 0.15 and 0.91 +/- 0.35% of the ingested
      dose was absorbed from the cereal fortified with NaFe(III)EDTA and FeSO4,
      respectively. Urinary excretion of 54Mn was very low; the total radioactivity in
      urine represented 1.1 +/- 0.55% of the absorbed dose with NaFe(III)EDTA and 0.72
      +/- 0.53% of the absorbed dose with FeSO4. Until now, Fe-fortification programs
      have met with only limited success. The introduction of NaFeEDTA as a food
      fortificant could be a useful tool to provide bioavailable Fe to vulnerable
      groups in the population and thus aid in combating Fe deficiency.

PMID- 9649598
TI  - Plasma lipid response to hypolipidemic diets in young healthy non-obese men
      varies with body mass index.
AB  - Lipid response to dietary fat is highly variable among individuals of a
      population. The aim of this study was to establish whether being overweight is
      one of the factors that determines this response. Forty-one non-obese healthy men
      were divided into two groups according to body mass index as follows: controls,
      <25 kg/m2; overweight, >25 kg/m2 but <30 kg/m2. After consuming a saturated fat
      rich diet (SAT diet: 38% fat, 20% saturated) for 4 wk, subjects were switched to
      a low fat diet [National Cholesterol Education Program (NCEP)-I diet: 28% fat,
      10% saturated] for 4 wk and then to a monounsaturated fat-rich diet (MUFA diet:
      38% fat, 22% monounsaturated) for 4 wk. Data were analyzed by Student's t test
      and two-way ANOVA for repeated measures. After consuming the NCEP-I diet, the
      overweight subjects had a smaller decrease relative to the SAT diet period in
      plasma total cholesterol [-0.30 vs. -0.67 mmol/L (-7 vs. -16%), P < 0.02] and low
      density lipoprotein-cholesterol concentrations [-0.24 vs. -0.55 mmol/L (-9 vs. 
      21%), P < 0.04] than controls. However, in the overweight subjects, the MUFA diet
      produced a greater decrease in plasma triglycerides than in the controls relative
      to the SAT diet period [-0.36 vs. -0.03 mmol/L (-26 vs. -4%), P < 0.006] and to
      the NCEP-I diet period [-0.29 vs. 0. 01 mmol/L (-22 vs. 1%), P < 0.01). Plasma
      cholesterol concentrations changed to a lesser extent, and triglyceride
      concentration to a greater extent, in overweight but non-obese young men than in
      those of normal weight in response to changes in dietary fat composition. Our
      data suggest that in the diet treatment of obese hyperlipemic subjects, it is
      more important for them to lose weight than to change the fat composition of
      their diets.

PMID- 9649599
TI  - alpha-Tocopherol concentrations in plasma but not in lipoproteins fluctuate
      during the menstrual cycle in healthy premenopausal women.
AB  - Because premenopausal women experience cyclic fluctuations of plasma carotenoids
      and their lipoprotein carriers, it was hypothesized that plasma alpha-tocopherol
      (A-T) fluctuates by phase of the menstrual cycle. Twelve free-living women, with
      a confirmed ovulatory cycle, were given a controlled diet for two consecutive
      menstrual cycles. Blood was drawn during the menses, early follicular, late
      follicular and luteal phases to simultaneously measure serum hormones, plasma
      lipoproteins and A-T concentrations, and A-T distribution in the lipoprotein
      fractions. Plasma A-T concentrations were significantly lower during menses than
      during the luteal phase by approximately 12% in each controlled diet cycle (P <
      0.001). Adjustment for serum cholesterol and triglyceride concentrations did not
      alter these findings. The distributions of A-T in lipoprotein cholesterol
      fractions were not significantly different by menstrual phase. From 61 to 62% of
      A-T was concentrated in the LDL fraction, with another 9-14% in HDL2, 17-22% in
      HDL3 and the remaining 6-8% in VLDL+ IDL. There were no significant differences
      in lipoprotein cholesterol fractions by menstrual phase, except for a significant
      increase (P = 0.03) in HDL2 cholesterol from the early follicular to the late
      follicular phase. Spearman rank correlations from data during the second
      controlled diet month showed A-T in HDL2 in the late follicular phase was
      positively correlated with HDL cholesterol in the early follicular (r = 0.88),
      late follicular (r = 0.86) and luteal phases (r = 0.86) and with luteal
      apolipoprotein (ApoA-1) level (r = 0.90), and luteal HDL2 cholesterol (r = 0.83).
      A-T in HDL3 in the early follicular phase was negatively correlated with HDL2
      cholesterol (r = -0.96) and ApoA-1 (r = -0.85), whereas luteal A-T in HDL3 was
      correlated with luteal HDL3 cholesterol (r = -0.79). Late follicular A-T in VLDL
      was positively correlated with early follicular HDL3 cholesterol and late
      follicular HDL3 cholesterol (r = 0.83). Fluctuations of A-T concentrations by
      phase of the menstrual cycle should be taken into consideration in future
      research concerning premenopausal women and the risk of chronic disease.

PMID- 9649600
TI  - Resistant proteins alter cecal short-chain fatty acid profiles in rats fed high
      amylose cornstarch.
AB  - The objective of this study was to examine the physiologic importance of
      undigested protein on cecal fermentation in rats fed a low (LAS) and high (HAS)
      amylose cornstarch. In Experiment 1, rats were fed diets containing LAS (655 g/kg
      diet) with one of four protein sources: casein, rice (RP), potato (PP) or soybean
      protein (SP) at 250 g/kg diet for 15 d. Apparent digestibilities of casein, RP,
      SP and PP were 96, 94, 93 and 92%, respectively. In rats fed the LAS diet with
      casein, acetate, propionate and succinate were the major cecal organic acids. The
      succinate pools in rats fed RP or SP were significantly lower than in those fed
      casein, whereas butyrate did not differ. Butyrate was significantly higher in
      rats fed PP, but succinate was the same as in rats fed casein. In Experiment 2,
      rats were fed diets containing HAS (200 g/kg diet) with one of the four protein
      sources at 250 g/kg diet for 10 d. HAS was substituted for the same amount of
      LAS. In rats fed the HAS diet, succinate was the major acid in rats fed casein;
      in rats fed RP or PP, however, the pools of this acid were significantly lower
      than in those fed casein, whereas butyrate was significantly higher in rats fed
      RP or PP. Fecal starch excretion was significantly lower in rats fed RP or PP
      than in those fed casein. In Experiment 3, rats were fed the casein-HAS diet with
      graded levels of PP (0, 10, 30, 50, 100 and 250 g/kg diet) for 14 d. The PP was
      substituted for the same amount of casein. Cecal butyrate was low in rats fed up
      to 100 g of PP/kg diet and then rose with 250 g of PP/kg diet. In Experiment 4,
      ileorectostomized rats were used and fed the same diets described in Experiment 3
      for 9 d. The ileal starch/nitrogen ratio declined with increasing dietary PP, due
      solely to greater nitrogen excretion, whereas starch excretion was unaffected. In
      Experiment 5, rats were fed the casein-HAS diet with or without 60 g of
      artificial resistant protein/kg diet for 10 d. The resistant protein (apparent
      digestibility, 63%) was substituted for the same amount of casein. Rats fed the
      casein-HAS diet with resistant protein had significantly greater cecal butyrate
      and lower succinate than those fed the casein-HAS diet. These data show that
      large bowel fermentation of starch is altered by dietary protein. They support
      the hypothesis that nondigested protein, namely, resistant protein, may control
      fermentation efficiency as well as the fermentation profile of HAS, possibly as a
      result of a change in microflora through the change in the ratio of starch to
      nitrogen in the cecum.

PMID- 9649601
TI  - Regulation of branched-chain amino acid metabolism in the lactating rat.
AB  - There is evidence that during lactation, uptake of the essential branched-chain
      amino acids (BCAA) by mammary glands exceeds their output in milk protein. In
      this study, we have measured the potential of lactating rats to catabolize BCAA.
      The activity, relative protein and specific mRNA levels of the first two enzymes
      in the BCAA catabolic pathway, branched-chain aminotransferase (BCAT) and
      branched-chain alpha-keto acid dehydrogenase (BCKD), were measured in mammary
      gland, liver and skeletal muscle obtained from rat dams at peak lactation (12 d),
      from rat dams 24 h after weaning at peak lactation and from age-matched virgin
      controls. Western analysis showed that the mitochondrial BCATm isoenzyme was
      found in mammary gland. Comparison of lactating and control rats revealed that
      tissue BCATm activity, protein and mRNA were at least 10-fold higher in mammary
      tissue during lactation. Values were 1.3- to 1. 9-fold higher after 24 h of
      weaning. In mammary gland of lactating rats, the BCKD complex was fully active.
      In virgin controls and weaning dams, only about 20% of the complex was in the
      active state. Hypertrophy of the liver and mammary gland during lactation
      resulted in a 73% increase in total oxidative capacity in lactating rats. The
      results are consistent with increased expression of the BCATm gene in the mammary
      gland during lactation, whereas oxidation appears to be regulated primarily by
      changes in activity state (phosphorylation state) of BCKD.

PMID- 9649602
TI  - Accumulation of (-)-epicatechin metabolites in rat plasma after oral
      administration and distribution of conjugation enzymes in rat tissues.
AB  - Absorption of orally administered (-)-epicatechin (EC) in rats was studied to
      obtain plasma pharmacokinetic profiles of EC metabolites. Rats were administered
      172 micromol/kg body weight of EC, and blood was collected from the tail for 8 h
      after administration. Seven groups of compounds possessing the basic structure of
      EC were identified by using a combination of enzymatic hydrolysis, HPLC and
      electron impact mass spectrometry. Metabolites were quantified with a new, simple
      and sensitive method using HPLC with electrochemical detection. Ingested EC was
      absorbed from the alimentary tract and was present in the rat common blood
      circulation in the form of glucuronide and/or sulfate conjugates. The activity of
      conjugative enzymes in rat tissues was studied. The highest activity of
      glucuronosyltransferase was found in the intestinal mucosa of both of the small
      and large intestine; the highest activity of phenolsulfotransferase occurred in
      the liver, and that of catechol-O-methyl transferase was found in the liver and
      kidney. It has been proposed that the first detoxification step of dietary EC,
      namely, glucuronidation, occurs at the level of the intestinal mucosa in rats,
      and EC enters the common blood circulation exclusively in the glucuronized form.
      The compound is then sulfated in the liver and methylated in the liver and
      kidney. Because ingested EC undergoes extensive conjugation, its biological
      activities previously demonstrated in vitro may not be occurring in in vivo
      systems.

PMID- 9649603
TI  - Tissue stores of beta-carotene are not conserved for later use as a source of
      vitamin A during compromised vitamin A status in mongolian gerbils (Meriones
      unguiculatus).
AB  - Vitamin A (VA) deficiency remains a serious problem in the world today. Current
      approaches to preventing or treating VA deficiency, including dietary
      intervention with provitamin A compounds, rely on the body converting ingested
      beta-carotene (betaC) to VA. However, it is not known whether betaC that is
      already in the tissues can be used as a source of VA to prevent deficiency. The
      objectives of these studies were to determine whether tissue betaC stores are
      converted to VA when the Mongolian gerbils have low VA status and whether
      previously fed betaC is retained in the tissues for later conversion to VA. In
      the first study, gerbils were prefed diets with betaC (20.3 +/- 6.2 nmol/g diet)
      (+betaC) or without betaC (-betaC), and with VA [2.4 +/- 1.5 nmol/g diet (+betaC
      diet) or 12.0 +/- 4.2 nmol/g diet (-betaC diet)] for 7 d, and then depleted of
      both betaC and VA for up to 84 d. On d 0 after the prefeeding period, hepatic
      betaC stores were 13.3 +/- 9.1 nmol. These stores were significantly lower after
      28d of consuming the -VA/-betaC diet (2.16 +/- 1.7 nmol), even though the hepatic
      VA concentrations did not change. In the second study, the gerbils were prefed a 
      VA/+betaC diet (74.3 +/- 19. 7 nmol betaC/g diet) for 7 d, and then fed a betaC
      free diet either with (7.1 +/- 1.4 nmol/g) or without VA for up to 34 d. Hepatic
      betaC stores after the 7-d prefeeding period were 38.1 +/- 20.6 nmol, and were
      significantly higher than after 7d of consuming either a +VA/-betaC (12.4 +/-
      10.8 mmol) or -VA/-betaC diet (11.4 +/- 8.0 nmol). The results from both studies
      suggest that a substantial amount of hepatic betaC is rapidly lost when betaC is
      eliminated from the diet and therefore is not conserved to meet later VA needs.
      The presence of VA in the diet (Study 2) did not affect the rate of betaC loss
      from the serum and tissues. Moreover, no evidence was found that the stored betaC
      was utilized for VA. The data suggest that there may be two pools of hepatic
      betaC, one that is lost rapidly and another that is lost more slowly over time,
      but losses are not affected by VA status.

PMID- 9649604
TI  - Feeding diets containing high levels of milk products or cellulose decrease
      urease activity and ammonia production in rat intestine.
AB  - Three studies were done to determine the effect of feeding diets containing high
      levels of a readily fermentable carbohydrate (lactose in milk or yogurt, or pure
      lactose) or an undigestible, unfermentable diluent (alpha-cellulose) on urease
      (EC 3.5.1.5) activity and net ammonia production in the rat gastrointestinal (GI)
      contents. Rats (170-200 g) were fed a control diet or diets containing 55% dried
      milk or 55% dried yogurt, 25% lactose or 10% alpha-cellulose. Feeding diets
      containing milk or yogurt decreased urease activity to approximately 11% of the
      control value in the small intestine (on the basis of grams of collected contents
      or total contents), and to 50% in the large intestine (only on the basis of grams
      of collected contents). Feeding the diet containing 25% lactose also decreased
      urease activity (on the basis of grams of collected contents or total contents)
      to about 20% of the control value in the small intestine, but not (P > 0.05) in
      the large intestine. Net ammonia production rate was correlated (r2 = 0.98) with
      urease activity in the large intestinal contents, and the rate of ammonia
      production from ureolysis represented about two thirds of the total. Feeding the
      cellulose diet decreased (P < 0.05) both urease activity and net ammonia
      production in the large intestine to approximately 30% of the control value.
      Weights of tissue and contents of the large intestine were much higher (P < 0.01)
      in rats fed diets containing milk products or lactose than in the control rats,
      but were not affected by consumption of the cellulose diet. Results of our
      studies indicate that feeding diets containing high levels of milk products
      (lactose) or cellulose reduces urease activity and net ammonia production in the
      rat intestine, and thus may be beneficial for improving animal and human health.

PMID- 9649605
TI  - Intestinal fermentation lessens the inhibitory effects of phytic acid on mineral
      utilization in rats.
AB  - The specific effects of phytic acid (PA) and resistant starch (RS) on mineral
      bioavailability, namely, Ca, Mg, Fe, Zn and Cu, were investigated in rats adapted
      to semipurified diets. The diets provided either 73 g/100 g digestible wheat
      starch (DS) alone, or 53 g/100 g DS plus 20 g/100 g crude potato starch (RS) and
      either 0 or 1.1 g/100 g PA. A period of 3 wk was first planned to adapt the rats
      to their respective diets. Compared with rats fed the DS diets, those fed the RS
      diets had significant cecal hypertrophy and an accumulation of short-chain fatty
      acids, together with greater cecal blood flow. RS enhanced the cecal absorption
      of Ca and Mg (from 0.15 to 0.55 micromol/min for Ca, and from 0.10 to 0.35
      micromol/min for Mg). Mineral balance was enhanced significantly by RS (Ca, +46%;
      Mg +50%; Fe +20%; Zn, + 33% and Cu, +61%). PA had no significant effect on Ca or
      Mg solubility and absorption in the cecum, and it failed to alter significantly
      Ca or Mg balance. The apparent absorption of Fe, Zn and Cu was significantly
      lower in rats fed the DS + PA diet than in rats fed the DS diet (Fe, -35%; Zn, 
      28%; and Cu, -31%). In rats adapted to the RS diet, the inhibitory effects of PA
      were practically abolished and the mineral balance was restored to the control
      values. We conclude that the negative effects of PA on mineral balance are
      relatively minor compared with the stimulatory effect of RS.

PMID- 9649606
TI  - Dietary psyllium increases fecal bile acid excretion, total steroid excretion and
      bile acid biosynthesis in rats.
AB  - Psyllium, a source of dietary fiber rich in soluble components results in lower
      serum cholesterol concentration in several species. Suggested mechanisms for the
      hypocholesterolemic effect include a greater excretion of fecal bile acids and
      total steroids, and up-regulation of bile acid biosynthesis. The activity of
      cholesterol 7alpha-hydroxylase (7alphaOHase), the rate limiting enzyme in bile
      acid biosynthesis, is higher in rats fed 5% psyllium. Whether this higher
      activity corresponds to an increase in mRNA levels has not been determined. Four
      groups of 10 rats were fed a semipurified diet containing 5% cellulose (CEL;
      control), 5% cellulose plus 1% cholic acid (CCA), 5% cellulose plus 2%
      cholestyramine (CHY) or 5% psyllium hydrocolloid (PSY) for 3 wk. Liver
      cholesterol concentration, fecal bile acid and total steroid excretion,
      7alphaOHase activity and 7alphaOHase mRNA levels were measured. Liver cholesterol
      content in rats fed CCA was significantly higher than in all other groups. Rats
      fed CHY and PSY had significantly lower liver cholesterol content than those fed
      CEL. Total fecal steroid and bile acid excretions were significantly greater in
      rats fed CCA, CHY and PSY than in those fed CEL. Activities and mRNA levels of
      7alphaOHase in rats fed CHY and PSY were significantly higher than in rats fed
      CEL or CCA. These data indicate that feeding psyllium to rats increases fecal
      bile acid and total steroid excretion as well as 7alphaOHase activity and
      7alphaOHase mRNA levels.

PMID- 9649607
TI  - Moderate folate depletion increases plasma homocysteine and decreases lymphocyte
      DNA methylation in postmenopausal women.
AB  - To determine the human folate requirement on the basis of changes in biochemical
      pathways, we studied the effect of controlled folate intakes on plasma
      homocysteine and lymphocyte DNA methylation and deoxynucleotide content in
      healthy postmenopausal women. Eight women (49-63 y of age) were housed in a
      metabolic unit and fed a low folate diet containing 56 microg/d of folate for 91
      d. Folate intake was varied by supplementing 55-460 microg/d of folic acid
      (pteroylglutamic acid) to the diet to provide total folate intake periods of 5 wk
      at 56 microg/d, 4 wk at 111 microg/d and 3 wk at 286-516 microg/d. A subclinical
      folate deficiency with decreased plasma folate was created during the first two
      periods. This resulted in significantly elevated plasma homocysteine and urinary
      malondialdehyde, and lymphocyte DNA hypomethylation. The folate depletion also
      resulted in an increased ratio of dUTP/dTTP in mitogen-stimulated lymphocyte DNA
      and decreased lymphocyte NAD, changes suggesting misincorporation of uracil into
      DNA and increased DNA repair activity. The DNA hypomethylation was reversed with
      286-516 microg/d of folate repletion, whereas the elevated homocysteine decreased
      with 516 but not 286 microg/d of folate. The results indicate that marginal
      folate deficiency may alter DNA composition and that the current RDA of 180
      microg/d may not be sufficient to maintain low plasma homocysteine concentrations
      of some postmenopausal women.

PMID- 9649608
TI  - Dorsomedial hypothalamic lesions alter intake of an imbalanced amino acid diet in
      rats.
AB  - Within 3 h of ingesting an imbalanced amino acid diet (IAAD), rats show
      attenuated intake. The associated conditioned taste aversion can be ameliorated
      by giving the serotonin3 receptor blocker, tropisetron (TROP). A recent c-fos
      study indicated that the dorsomedial hypothalamic nucleus (DMN) may be activated
      2-3 h after ingestion of IAAD. In Experiment 1, DMN-lesioned rats (DMNL) or sham
      operated (SHAM) rats were injected with saline (SAL) or TROP just before
      introduction of IAAD. By 3 h, SAL-DMNL rats consumed more (P < 0.01) of the IAAD
      than did the SAL-SHAM rats. Thereafter, over the next 21 h, the intake of the SAL
      DMNL group returned to control levels. TROP treatment enhanced the intake of the
      treated groups; the TROP and the lesion effect were additive (P < 0.01). By d 4
      of receiving the IAAD, the DMNL groups were eating less than SHAM rats (P <
      0.05). The data suggest that the DMN may be involved in the early detection of
      the amino acid deficiency induced by IAAD, is not involved in the TROP effect and
      is necessary for proper long-term adaptation to an IAAD.

PMID- 9649609
TI  - Zinc deficiency increases hypothalamic neuropeptide Y and neuropeptide Y mRNA
      levels and does not block neuropeptide Y-induced feeding in rats.
AB  - Zinc deficiency reduces intake and produces an unusual approximately 3.5-d cycle
      of intake in rats. The mechanism underlying the anorexia and cycling has not yet
      been defined; current hypotheses suggest that alterations in amino acid
      metabolism and neurotransmitter concentrations may be a part of this anorexia.
      Recent reports indicate that appetite-stimulating neuropeptide Y (NPY) may be
      elevated during zinc deficiency. This suggests that a resistance to NPY may exist
      during zinc deficiency because NPY levels are high, yet appetite is low. The
      purpose of this study was to measure NPY peptide and mRNA concentrations during
      zinc deficiency in specific nuclei of the hypothalamus in which peptide and mRNA
      for NPY are known to be associated with appetite, and also to determine whether
      zinc-deficient rats are responsive to central infusions of NPY. Both NPY peptide
      levels in the paraventricular nucleus and NPY mRNA levels in the arcuate nucleus
      were higher (P < 0.05) in zinc-deficient rats than in zinc-adequate rats. When
      rats were administered exogenous NPY to the paraventricular nucleus, both zinc
      deficient and zinc-adequate rats responded similarly by increasing food intake.
      These results suggest that NPY is elevated during zinc deficiency in an attempt
      to restore normal food intake levels, rather than being reduced and thereby
      contributing to the anorexia associated with zinc deficiency. During zinc
      deficiency, NPY receptors are able to bind NPY and initiate an orexigenic
      response.

PMID- 9649610
TI  - Prenatal malnutrition-induced functional alterations in callosal connections and
      in interhemispheric asymmetry in rats are prevented by reduction of noradrenaline
      synthesis during gestation.
AB  - Prenatal malnutrition results in increased concentration and release of central
      noradrenaline, a neurotransmitter that is an important regulator of normal
      regressive events such as axonal pruning and synaptic elimination. This suggests
      that some of the functional disturbances in brain induced by prenatal
      malnutrition could be due at least in part to increased noradrenaline activity
      that may enhance regressive events during early stages of development. To test
      this hypothesis we studied whether chronic administration of alpha-methyl-p
      tyrosine, an inhibitor of tyrosine hydroxylase, to rats during gestation might
      prevent long-term deleterious effects of prenatal malnutrition on functional
      properties of interhemispheric connections of the visual cortex, and on asymmetry
      of visual evoked responses. The experiments were conducted on normal and
      malnourished rats 45-50 d of age. Prenatal malnutrition was induced by
      restricting the food consumption of pregnant rats to 40%, from d 8 postconception
      to parturition. At birth, prenatally malnourished rats had significantly greater
      whole-brain noradrenaline concentration as well as significantly enhanced
      noradrenaline release in the visual cortex. At 45-50 d of age, the malnourished
      group had a significantly smaller cortical area, exhibiting transcallosal evoked
      responses; in addition, the amplitude of these responses was significantly
      smaller. Malnourished rats showed a significant reduction of the normal
      interhemispheric asymmetry of visual evoked responses. The addition of 0.3% alpha
      methyl-p-tyrosine to the diet of malnourished pregnant rats during the last 2 wk
      of gestation prevented functional disorders induced in the offspring by prenatal
      malnutrition on interhemispheric connectivity of visual areas and on
      interhemispheric bioelectrical asymmetry, probably by reducing the elevated brain
      noradrenaline activity and thereby restoring the normal trophic role of this
      neurotransmitter.

PMID- 9649611
TI  - Calcium-deprived rats avoid sweet compounds.
AB  - To characterize the link between calcium status and sweet solution intake, rats
      fed a diet containing 25 mmol Ca2+/kg (Ca-25, low calcium) or 150 mmol Ca2+/kg
      (Ca-150, control) were given 48-h two-bottle tests with a choice between water
      and various concentrations of a nutrient (sucrose, Polycose, ethanol and/or corn
      oil). Rats fed the Ca-25 diet had significantly lower sucrose intakes and
      preferences over the entire range tested (10-320 g/L) even though the same
      (Experiment 1), or identically treated (Experiment 2a) rats had normal Polycose
      and ethanol intakes and normal (Experiment 1, 2b) or significantly greater
      (Experiment 2a) corn oil intakes. In additional tests, rats fed the Ca-25 diet
      had significantly lower intakes relative to rats fed the Ca-150 diet of other
      sweeteners (30 mmol/L D-phenylalanine, 1 mmol/L saccharin and 0.3 mmol/L
      aspartame), significantly higher intakes of 0.5 mg/L capsaicin and 300 mmol/L
      monosodium glutamate, and normal intakes of 10 g/L or 80 g/L safflower oil and 10
      g/L peanut oil. In a three-cup macronutrient selection experiment (Experiment 3),
      calcium-deprived rats ate significantly less of a high sucrose carbohydrate
      source and significantly more of a protein source than did controls. These
      results suggest that calcium deficiency reduces the rat's liking for sweetness,
      irrespective of the type or form of sweetener, and that this is not due to a
      general reduction in energy intake.

PMID- 9649612
TI  - Zinc pretreatment inhibits isotretinoin teratogenicity and induces embryonic
      metallothionein in CD-1 mice.
AB  - Isotretinoin (ITR), a teratogen in many species, is associated with increased
      oxidative stress. Metallothionein (MT) is an important tissue antioxidant whose
      concentrations are induced by zinc. To study the role of supplemental Zn as an
      inducer of embryonic MT, we injected pregnant CD-1 mice subcutaneously with
      saline vehicle, or 20 or 40 mg/kg Zn on gestational day (GD) 6.5. After 48 h,
      embryonic MT concentrations increased in a dose-related manner (r = 0.64, P <
      0.05) with Zn treatment. The possible protective role of Zn pretreatment against
      ITR teratogenicity was investigated in vivo and in vitro. CD-1 mice were
      pretreated with saline or Zn (20 and 40 mg/kg) on GD 8.5 and 9.5. ITR was
      administered to both groups of mice via three intragastric intubations of 100 mg
      ITR/kg at 4 h intervals on GD 10.5. On GD 18.5, Zn pre-treated mice demonstrated
      decreased ITR-mediated growth retardation, cleft palates and postpartum
      mortality. A reduction in embryonic MT concentrations was observed in mice
      exposed to ITR. Mouse embryos cultured on GD 8.5 with an addition of 15
      micromol/L Zn for 48 h had a sixfold greater MT concentration (688 microg/g
      protein) than controls. The Zn pretreatment of cultured embryos prevented
      malformations and lessened growth retardation caused by 24 h exposure to 17
      micromol/L ITR. These results suggest that Zn-mediated induction of MT in mouse
      embryos could protect against ITR teratogenicity.

PMID- 9649613
TI  - Cytoplasmic ribosomal protein genes of the fission yeast Schizosaccharomyces
      pombe display a unique promoter type: a suggestion for nomenclature of
      cytoplasmic ribosomal proteins in databases.
AB  - We identified 34 new ribosomal protein genes in the Schizosaccharomyces pombe
      database at the Sanger Centre coding for 30 different ribosomal proteins. All
      contain the Homol D-box in their promoter. We have shown that Homol D is, in this
      promoter type, the TATA-analogue. Many promoters contain the Homol E-box, which
      serves as a proximal activation sequence. Furthermore, comparative sequence
      analysis revealed a ribosomal protein gene encoding a protein which is the
      equivalent of the mammalian ribosomal protein L28. The budding yeast
      Saccharomyces cerevisiae has no L28 equivalent. Over the past 10 years we have
      isolated and characterized nine ribosomal protein (rp) genes from the fission
      yeast S.pombe . This endeavor yielded promoters which we have used to investigate
      the regulation of rp genes. Since eukaryotic ribosomal proteins are remarkably
      conserved and several rp genes of the budding yeast S.cerevisiae were sequenced
      in 1985, we probed DNA fragments encoding S.cerevisiae ribosomal proteins with
      genomic libraries of S.pombe . The deduced amino acid sequence of the different
      isolated rp genes of fission yeast share between 65 and 85% identical amino acids
      with their counterparts of budding yeast.

PMID- 9649614
TI  - Thermal stability of DNA.
AB  - Tij and Delta Hij for stacking of pair i upon j in DNA have been obtained over
      the range 0.034-0.114 M Na+from high-resolution melting curves of well-behaved
      synthetic tandemly repeating inserts in recombinant pN/MCS plasmids. Results are
      consistent with neighbor-pair thermodynamic additivity, where the stability
      constant, sij , for different domains of length N depend quantitatively on the
      product of stability constants for each individual pair in domains, sijN . Unit
      transition enthalpies with average errors less than +/-5%, were determined by
      analysis of two-state equilibria associated with the melting of internal domains
      and verified from variations of Tij with [Na+]. Enthalpies increase with Tij , in
      close agreement with the empirical function: Delta Hij = 52.78@ Tij - 9489, and
      in parallel with a smaller increase in Delta Sij . Delta Hij and Delta Sij are in
      good agreement with the results of an extensive compilation of published Delta
      Hcal and Delta Scal for synthetic and natural DNAs. Neighbor-pair additivity was
      also observed for (dA@dT)-tracts at melting temperatures; no evidence could be
      detected of the familiar and unusual structural features that characterize tracts
      at lower temperatures. The energetic effects of loops were determined from the
      melting behavior of repeating inserts installed between (G+C)-rich barrier
      domains in the pN/MCS plasmids. A unique set of values for the cooperativity,
      loop exponent and stiffness parameters were found applicable to internal domains
      of all sizes and sequences. Statistical mechanical curves calculated with values
      of Tij([Na+]) , Delta Hij and these loop parameters are in good agreement with
      observation.

PMID- 9649615
TI  - Comparative structure analysis of vertebrate ribonuclease P RNA.
AB  - Ribonuclease P cleaves 5'-precursor sequences from pre-tRNAs. All cellular RNase
      P holoenzymes contain homologous RNA elements; the eucaryal RNase P RNA, in
      contrast to the bacterial RNA, is catalytically inactive in the absence of the
      protein component(s). To understand the function of eucaryal RNase P RNA,
      knowledge of its structure is needed. Considerable effort has been devoted to
      comparative studies of the structure of this RNA from diverse organisms,
      including eucaryotes, primarily fungi, but also a limited set of vertebrates. The
      substantial differences in the sequences and structures of the vertebrate RNAs
      from those of other organisms have made it difficult to align the vertebrate
      sequences, thus limiting comparative studies. To expand our understanding of the
      structure of diverse RNase P RNAs, we have isolated by PCR and sequenced 13
      partial RNase P RNA genes from 11 additional vertebrate taxa representing most
      extant major vertebrate lineages. Based on a recently proposed structure of the
      core elements of RNase P RNA, we aligned the sequences and propose a minimum
      consensus secondary structure for the vertebrate RNase P RNA.

PMID- 9649616
TI  - Localised sequence regions possessing high melting temperatures prevent the
      amplification of a DNA mimic in competitive PCR.
AB  - The polymerase chain reaction is an immensely powerful technique for
      identification and detection purposes. Increasingly, competitive PCR is being
      used as the basis for quantification. However, sequence length, melting
      temperature and primary sequence have all been shown to influence the efficiency
      of amplification in PCR systems and may therefore compromise the required
      equivalent co-amplification of target and mimic in competitive PCR. The work
      discussed here not only illustrates the need to balance length and melting
      temperature when designing a competitive PCR assay, but also emphasises the
      importance of careful examination of sequences for GC-rich domains and other
      sequences giving rise to stable secondary structures which could reduce the
      efficiency of amplification by serving as pause or termination sites. We present
      data confirming that under particular circumstances such localised sequence, high
      melting temperature regions can act as permanent termination sites, and offer an
      explanation for the severity of this effect which results in prevention of
      amplification of a DNA mimic in competitive PCR. It is also demonstrated that
      when Taq DNA polymerase is used in the presence of betaine or a proof reading
      enzyme, the effect may be reduced or eliminated.

PMID- 9649617
TI  - BfiI, a restriction endonuclease from Bacillus firmus S8120, which recognizes the
      novel non-palindromic sequence 5'-ACTGGG(N)5/4-3'.
AB  - A new type IIS restriction endonuclease Bfi I hasbeen partially purified from
      Bacillus firmus S8120. Bfi I recognizes the non-palindromic hexanucleotide
      sequence 5'-ACTGGG(N)5/4-3' and makes a staggered cut at the fifth base pair
      downstream of the recognition sequence on the upper strand, producing a single
      base 3' protruding end.

PMID- 9649618
TI  - Biophysical and antisense properties of oligodeoxynucleotides containing 7
      propynyl-, 7-iodo- and 7-cyano-7-deaza-2-amino-2'-deoxyadenosines.
AB  - The synthesis of 7-propynyl-, 7-iodo- and 7-cyano-7-deaza-2-amino-2'
      deoxyadenosines is described. The nucleosides were synthesized, functionalized
      into the phosphoramidites and incorporated into oligodeoxynucleotides.
      Spectroscopic melting experiments against complementary RNA showed increases of 3
      4 degreesC per modification for single substitutions and smaller increases per
      incorporation for multiple substitutions relative to unmodified control
      sequences. The 7-propyne and 7-iodo nucleosides were incorporated into antisense
      sequences targeting the 3'-UTR of murine C- raf mRNA. Both nucleosides
      demonstrated substitution-dependent potency. The sequences with three and four
      substitutions of the 7-propyne-7-deaza-2-amino-2'-deoxyadenosine exhibited a 2-3
      fold increase in potency over unmodifed controls.

PMID- 9649619
TI  - Eosinophil cationic protein/RNase 3 is another RNase A-family ribonuclease with
      direct antiviral activity.
AB  - Eosinophil cationic protein (ECP) is one of two RNase A-superfamily ribonucleases
      found in secretory granules of human eosinophilic leukocytes. Although the
      physiologic function of eosinophils [and thus of the two eosinophil
      ribonucleases, ECP and eosinophil-derived neurotoxin (EDN)] remains
      controversial, we have recently shown that isolated human eosinophils promote
      ribonuclease-dependent toxicity toward extracellular virions of the single
      stranded RNA virus, respiratory syncytial virus, group B (RSV-B). We have also
      shown that recombinant human EDN (rhEDN) can act alone as a ribonuclease
      dependent antiviral agent. In this work, we provide a biochemical
      characterization of recombinant human ECP (rhECP) prepared in baculovirus, and
      demonstrate that rhECP also promotes ribonuclease-dependent antiviral activity.
      The rhECP described here is N-glycosylated, as is native ECP, and has
      approximately 100-fold more ribonuclease activity than non-glycosylated rhECP
      prepared in bacteria. The enzymatic activity of rhECP was sensitive to inhibition
      by placental ribonuclease inhibitor (RI). Although rhECP was not as effective as
      rhEDN at reducing viral infectivity (500 nM rhECP reduced infectivity of RSV-B
      approximately 6 fold; 500 nM rhEDN, >50 fold), the antiviral activity appears to
      be unique to the eosinophil ribonucleases; no reduction in infectivity was
      promoted by bovine RNase A, by the amphibian ribonuclease, onconase, nor by the
      closely-related human ribonuclease, RNase k6. Interestingly, combinations of
      rhEDN and rhECP did not result in either a synergistic or even an additive
      antiviral effect. Taken together, these results suggest that that the interaction
      between the eosinophil ribonucleases and the extracellular virions of RSV-B may
      be specific and saturable.

PMID- 9649620
TI  - Novel site-specific DNA modification in Streptomyces: analysis of preferred
      intragenic modification sites present in a 5.7 kb amplified DNA sequence.
AB  - Both Streptomyces lividans and Streptomyces avermitilis encode similar systems of
      post-replicative DNA modification which act site-specifically on closely opposed
      guanines on either strand. The modifications can be detected since they react in
      vitro with an oxidative derivative of Tris, resulting in strand cleavage.
      Previous analysis of the preferred modification site of plasmid pIJ101 indicated
      that extensive amounts of flanking sequence, including direct and inverted repeat
      structures, are required to direct modification in vivo within a central 6 bp
      palindrome. We have now examined the preferred modification sites of a
      chromosomal element, the 5.7 kb amplified DNA sequence (ADS5.7) found in certain
      S. lividans mutants. In contrast to the pIJ101 site, each of the ADS5. 7sites is
      intragenic and modified with a 10-fold reduced frequency. However, similar
      extents of flanking sequence are required for authentic double-strand
      modification; deletion mutants exhibited different modification profiles,
      including displaced double-stranded or single-stranded modi-fication. Comparison
      of different modification sites reveals conservation of the central core
      sequence, but no significant similarities between flanking sequences. Enhanced
      modification was detected in a cloned region of the ADS5.7, suggesting that local
      DNA topology, probably influenced by both DNA supercoiling and the nature of
      flanking sequences, can influence the modifying activity.

PMID- 9649621
TI  - Linear amplicons as precursors of amplified circles in methotrexate-resistant
      Leishmania tarentolae.
AB  - Gene amplification is frequently observed in Leishmania cells selected for drug
      resistance. By gene targeting we have tagged both alleles of the H locus of
      Leishmania tarentolae with the neomycin and hygromycin phosphotransferase genes (
      neo and hyg ). Selection of these recombinant parasites for low level
      methotrexate resistance led to amplification of the H locus as part of linear
      amplicons. The availability of tags has permitted us to determine that both
      alleles can be amplified in the same cell and that chromosomal deletions are
      frequent. When methotrexate concentration was increased in subsequent selection
      steps, circles were observed in several mutants. We have introduced a hyg marker
      into linear amplicons to test whether the circles originated from linear
      amplicons. After selection with a high methotrexate concentration, circles with
      the hyg marker were observed, showing that circles can indeed be formed from
      linear amplicons. The tagging of H locus alleles permits appreciation of the
      extent of genetic rearrangements leading to amplicon formation in Leishmania
      cells selected for drug resistance.

PMID- 9649622
TI  - Allosteric regulation of a ribozyme activity through ligand-induced
      conformational change.
AB  - An allosteric ribozyme has been designed using the hammerhead ribozyme as the
      active site and aflavin-specific RNA aptamer as a regulatory site. We constructed
      six variants with a series of base pairs in the linker region (stem II). Under
      single turnover conditions, kinetic studies were carried out in the absence and
      presence of flavin mononucleotide (FMN). Interestingly, FMN addition did not
      influence the cleavage rate of constructs with a 5-6 bp linker but stimulated the
      catalytic activity of those bearing a shorter linker. In particular, the apparent
      k cat of Rz3 increases by approximately 10-fold upon addition of saturating
      amounts of FMN. To determine the rate constants( K m4and k cat), the ribozyme
      regulated most effectively by FMN was further investigated. FMN mainly affected
      the k cat value, reflecting the rate limiting conformational change step of the
      overall cleavage reaction, depending on helix formation in stem II. Probably, FMN
      influences the orientation of structures necessary for the cleavage reaction
      through stem II formation. The result of chemical modification revealed that
      binding of FMN to the aptamer domain induced the helix formation in stem II
      required for catalytic activity. Therefore, a specific FMN-mediated allosteric
      interaction seems to promote a conformational alteration from an open to a closed
      structure in stem II. The concept of conformational modification in the
      allosteric effect is consistent with other allosteric enzymes, suggesting that
      such a conformational change is a fundamental feature of allosteric enzymes in
      biological systems.

PMID- 9649623
TI  - Effects of helical structures formed by the binding arms of DNAzymes and their
      substrates on catalytic activity.
AB  - As a part of our efforts to clarify structure-function relationships in reactions
      catalyzed by deoxyribozymes (DNAzymes), which were recently selected in vitro ,
      we synthesized various chimeras and analyzed the kinetics of the corresponding
      cleavage reactions. We focused on the binding arms and generated helices composed
      of binding arms and substrates that consisted of RNA and RNA, of RNA and DNA or
      of DNA and DNA. As expected for the rate limiting chemical cleavage step in
      reactions catalyzed by DNAzymes, a linear relationship between log( k cat) and pH
      was observed. In all cases examined, introduction of DNA into the binding helix
      enhanced the rate of chemical cleavage. Comparison of CD spectra of DNAzyme.
      substrate complexes suggested that higher levels of B-form-like helix were
      associated with higher rates of cleavage of the substrate within the complex. To
      our surprise, the enhancement of catalytic activity that followed introduction of
      DNA into the binding helix (enhancement by the presence of more B-form-like
      helix) was very similar to that observed in the case of the hammerhead ribozymes
      that we had investigated previously. These data, together with other
      observations, strongly suggest that the reaction mechanism of metal-ion-dependent
      DNAzymes is almost identical to that of hammerhead ribozymes.

PMID- 9649624
TI  - Metal ion-dependent hydrolysis of RNA phosphodiester bonds within hairpin loops.
      A comparative kinetic study on chimeric ribo/2'-O-methylribo oligonucleotides.
AB  - Several chimeric ribo/2'- O -methylribo oligonucleotides were synthesized and
      their hydrolytic cleavage studied in the presence of Mg2+, Zn2+, Pb2+and the
      1,4,9-triaza-cyclododecane chelate of Zn2+(Zn2+[12]aneN3) to evaluate the
      importance of RNA secondary structure as a factor determining the reactivity of
      phosphodiester bonds. In all the cases studied, a phosphodiester bond within a 4
      7 nt loop was hydrolytically more stable than a similar bond within a linear
      single strand, but markedly less stable than that in a double helix. With Zn2+and
      Zn2+[12]aneN3, the hydrolytic stability of a phosphodiester bond within a hairpin
      loop gradually decreased on increasing the distance from the stem. A similar but
      less systematic trend was observed with Pb2+. Zn2+- and Pb2+-promoted cleavage
      was observed to be considerably more sensitive to the secondary structure of the
      chain than that induced by Zn2+[12]aneN3. This difference in behaviour may be
      attributed to bidentate binding of uncomplexed aquo ions to two different
      phosphodiester bonds. Mg2+was observed to be catalytically virtually inactive
      compared with the other cleaving agents studied.

PMID- 9649626
TI  - Automated detection of point mutations using fluorescent sequence trace
      subtraction.
AB  - The final step in the detection of mutations is to determine the sequence of the
      suspected mutant and to compare it with that of the wild-type, and for this
      fluorescence-based sequencing instruments are widely used. We describe some
      simple algorithms forcomparing sequence traces which, as part of our sequence
      assembly and analysis package, are proving useful for the discovery of mutations
      and which may also help to identify misplaced readings in sequence assembly
      projects. The mutations can be detected automatically by a new program called
      TRACE_DIFF and new types of trace display in our program GAP4 greatly simplify
      visual checking of the assigned changes. To assess the accuracy of the automatic
      mutation detection algorithm we analysed 214 sequence readings from hypermutating
      DNA comprising a total of 108 497 bases. After the readings were assembled there
      were 1232 base differences, including 392 Ns and 166 alignment characters. Visual
      inspection of the traces established that of the 1232 differences, 353 were real
      mutations while the rest were due to base calling errors. The TRACE_DIFF
      algorithm automatically identified all but 36, with 28 false positives. Further
      information about the software can be obtained from http://www.mrc
      lmb.cam.ac.uk/pubseq/

PMID- 9649625
TI  - Rapid changes of nucleotide excision repair gene expression following UV
      irradiation and cisplatin treatment of Dictyostelium discoideum.
AB  - Organisms use different mechanisms to detect and repair different types of DNA
      damage, and different species vary in their sensitivity to DNA damaging agents.
      The cellular slime mold Dictyostelium discoideum has long been recognized for its
      unusual resistance to UV and ionizing radiation. We have recently cloned three
      nucleotide excision repair (NER) genes from Dictyostelium , the rep B, D and E
      genes (the homologs of the human xeroderma pigmentosum group B, D and E genes,
      respectively). Each of these genes has a unique pattern of expression during the
      multicellular development of this organism. We have now examined the response of
      these genes to DNA damage. The rep B and D DNA helicase genes are rapidly and
      transiently induced in a dose dependent manner following exposure to both UV
      light and the widely used chemotherapeutic agent cisplatin. Interestingly, the
      rep E mRNA level is repressed by UV but not by cisplatin, implying unique signal
      transduction pathways for recognizing and repairing different types of damage.
      Cells from all stages of growth and development display the same pattern of NER
      gene expression following exposure to UV-light. These results suggest that the
      response to UV is independent of DNA replication, and that all the factors
      necessary for rapid transcription of these NER genes are either stable throughout
      development, or are continuously synthesized. It is significant that the up
      regulation of the rep B and D genes in response to UV and chemical damage has not
      been observed to occur in cells from other species. We suggest that this rapid
      expression of NER genes is at least in part responsible for the unusual
      resistance of Dictyostelium to DNA damage.

PMID- 9649627
TI  - Oligonucleotide binding specificities of the hnRNP C protein tetramer.
AB  - Through the use of various non-equilibrium RNA binding techniques, the C protein
      tetramer of mammalian40S hnRNP particles has been characterized previously as a
      poly(U) binding protein with specificity for the pyrimidine-rich sequences that
      often precede 3' intron-exon junctions. C protein has also been characterized as
      a sequence-independent RNA chaperonin that is distributed along nascent
      transcripts through cooperative binding and as a protein ruler that defines the
      length of RNA packaged in 40S monoparticles. In this study fluorescence
      spectroscopy was used to monitor C protein-oligonucleotide binding in a
      competition binding assay under equilibrium conditions. Twenty nucleotide
      substrates corresponding to polypyrimidine tracts from IVS1 of the adenovirus-2
      major late transcript, the adenovirus-2 oncoprotein E1A 3' splice site, IVS2 of
      human alpha-tropomyosin, the consensus polypyrimidine tract for U2AF65, AUUUA
      repeats and r(U)20were used as competitors. A 20 nt beta-globin intronic sequence
      and a randomly generated oligo were used as competitor controls. These studies
      reveal that native C protein possesses no enhanced affinity for uridine-rich
      oligonucleotides, but they confirm the enhanced affinity of C protein for an
      oligonucleotide identified as a high affinity substrate through selection and
      amplification. Evidence that the affinity of C protein for the winner sequence is
      due primarily to its unique structure or to a unique context is seen in its
      retained substrate affinity when contiguous uridines are replaced with contiguous
      guanosines.

PMID- 9649628
TI  - hnRNP C increases amyloid precursor protein (APP) production by stabilizing APP
      mRNA.
AB  - We have previously shown that heterogeneous nuclear ribonucleoprotein C (hnRNP C)
      and nucleolin bound specifically to a 29 nt sequence in the 3'-untranslated
      region of amyloid precursor protein (APP) mRNA. Upon activation of peripheral
      blood mononuclear cells, hnRNP C and nucleolin acquired APP mRNA binding
      activity, concurrent with APP mRNA stabilization. These data suggested that the
      regulated interaction of hnRNP C and nucleolin with APP mRNA controlled its
      stability. Here we have directly examined the role of the cis element and trans
      factors in the turnover and translation of APP mRNA in vitro . In a rabbit
      reticulocyte lysate (RRL) translation system, a mutant APP mRNA lacking the 29 nt
      element was 3-4-fold more stable and synthesized 2-4-fold more APP as wild-type
      APP mRNA. Therefore, the 29 nt element functioned as an APP mRNA destabilizer.
      RNA gel mobility shift assays with the RRL suggested the presence of endogenous
      nucleolin, but failed to show hnRNP C binding activity. However, wild-type APP
      mRNA was stabilized and coded for 6-fold more APP when translated in an RRL
      system supplemented with exogenous active hnRNP C. Control mRNAs lacking the 29
      nt element were unaffected by hnRNP C supplementation. Therefore, occupancy of
      the 29 nt element by hnRNP C stabilized APP mRNA and enhanced its translation.

PMID- 9649629
TI  - Topological complexity of different populations of pBR322 as visualized by two
      dimensional agarose gel electrophoresis.
AB  - Neutral/neutral two-dimensional (2D) agarose gelelectrophoresis was used to
      investigate populations of the different topological conformations that pBR322
      can adopt in vivo in bacterial cells as well as in Xenopus egg extracts. To help
      in interpretation and identification of all the different signals, undigested as
      well as DNA samples pretreated with DNase I, topoisomerase I and topoisomerase II
      were analyzed. The second dimension of the 2D gel system was run with or without
      ethidium bromide to account for any possible changes in the migration behavior of
      DNA molecules caused by intercalation of this planar agent. Finally, DNA samples
      were isolated from a recA-strain of Escherichia coli , as well as after direct
      labeling of the replication intermediates in extracts of Xenopus laevis eggs.
      Altogether, the results obtained demonstrated that 2D gels can be readily used to
      identify most of the complex topological populations that circular molecules can
      adopt in vivo in both bacteria and eukaryotic cells.

PMID- 9649630
TI  - Pausing of reverse transcriptase on retroviral RNA templates is influenced by
      secondary structures both 5' and 3' of the catalytic site.
AB  - In the most extensive examination to date of the relationship between the pausing
      of reverse transcrip-tase (RT) and RNA secondary structures, pause events were
      found to be correlated to inverted repeats both ahead of, and behind the
      catalytic site in vitro. In addition pausing events were strongly associated with
      polyadenosine sequences and to a lesser degree diadenosines and monoadenosine
      residues. Pausing was also inversely proportional to the potential bond strength
      between the nascent strand and the template at the point of termination, for both
      mono and dinucleotides. A run of five adenosine and four uridine residues caused
      most pausing on the HIV-1 template, a region which is the site of much sequence
      heterogeneity in HIV-1. We propose that homopolyadenosine tracts can act as
      termination signals for RT in the context of inverted repeats as they do for
      certain RNA polymerases.

PMID- 9649631
TI  - A reliable way of obtaining stable inducible clones.
AB  - Inducible gene expression systems provide a powerful tool for the analysis of
      gene product functions. The 'Tetracycline (Tc) expression system' has been widely
      and successfully used in many instances. However, this system remains somewhat
      tedious to use due to: (i) the establishment of a primary cell line
      constitutively and stably expressing the Tc-regulated transactivator and (ii) the
      obtention of a secondary line expressing the gene of interest in a Tc-dependent
      manner. In order to facilitate these two critical steps, we devised an efficient
      and molecular biology-free strategy allowing the successful selection of clones
      expressing any cDNA under tight regulation.

PMID- 9649632
TI  - Enhanced concatemer cloning-a modification to the SAGE (Serial Analysis of Gene
      Expression) technique.
AB  - The Serial Analysis of Gene Expression (SAGE) method, described in 1995 by
      Velculescu et al ., represents a powerful means to compare gene expression
      between two mRNA populations. An improvement to SAGE that removes contaminating
      linker molecules, which compromise the efficiency of the method, has been
      developed. This modification utilises biotinylated PCR primers, which generate
      biotinylated linkers at an early stage in the SAGE protocol, thus allowing
      removal of the unwanted linkers by binding to streptavidin-coated magnetic beads
      at a later stage. The application of this modification resulted in the rapid
      generation of high ditag yields and clones with large average insert sizes.

PMID- 9649633
TI  - Efficient modification of a human chromosome by telomere-directed truncation in
      high homologous recombination-proficient chicken DT40 cells.
AB  - Truncation of human chromosomes at desired sites by homologous recombination
      techniques enables functional and structural analyses of human chromosomes and
      development of human artificial chromosomes. However, this targeted truncation
      has been inefficient. We describe here an efficient method for targeted
      truncation in the chicken DT40 cells with a high homologous recombination rate.
      The human chromosome 22 was transferred into DT40 cells, where human telomeric
      repeat (TTAGGG)n was targeted to the LIF locus on the chromosome. Molecular and
      cytogenetic analyses showed that the predicted truncation at the LIF locus
      occurred in all of the targeted clones.

PMID- 9649634
TI  - Chemical mapping of co-existing RNA structures.
AB  - In many cases RNA can assume co-existing or meta-stable structures preventing
      structure determination by chemical mapping. A novel method is described, by
      which RNA is modified with dimethyl sulphate without shifting the distribution of
      different structures. The different structures are then separated in native gel
      electrophoresis, and structure determination by primer extension can be carried
      out separately for each structure.

PMID- 9649635
TI  - Solid-phase cDNA library construction, a versatile approach.
AB  - A rapid and versatile method for cDNA library construction was developed. It is
      based on conventional cDNA library synthesis including all enzymatic steps
      usually required, but is performed on a solid support. The cDNA is immobilised
      via a biotin residue to streptavidin coupled magnetic beads, which allows rapid
      and easy to perform changes of buffers and enzymes. Therefore, it combines speed
      (library construction within a single day) with high quality libraries, making it
      ideally suited for most purposes.

PMID- 9649636
TI  - Dobutamine stress echocardiography for preoperative cardiac risk stratification
      in patients undergoing orthotopic liver transplantation.
AB  - This study attempts to evaluate the efficacy of dobutamine stress
      echocardiography for preoperative cardiac risk stratification in patients
      undergoing orthotopic liver transplantation. Two hundred twenty consecutively
      submitted patients were evaluated in preparation for orthotopic liver
      transplantation. Dobutamine stress echocardiography was performed in 80 patients
      with known or suspected coronary artery disease. Follow-up information was
      available in 40 patients in the form of cardiac catheterization and/or outcome
      from liver transplantation to validate the dobutamine stress echo findings. The
      prevalence of coronary artery disease in this cohort was 5% and was closely
      associated with the presence of diabetes mellitus. Dobutamine stress
      echocardiography, when interpreted as abnormal in the presence of wall motion
      abnormalities only, is associated with a sensitivity, specificity, and positive
      and negative predictive value of 100%. Dobutamine stress echocardiography is
      highly efficacious and should be the screening study of choice to detect coronary
      artery disease in patients undergoing orthotopic liver transplantation.

PMID- 9649637
TI  - Biliary lipid composition after liver transplantation: effect of allograft
      function and cyclosporine.
AB  - Biliary lipid composition and bile flow are altered after orthotopic liver
      transplantation. Cyclosporine may have additional effects on biliary lipid
      composition and secretion. We studied the effects of liver transplantation,
      allograft function, and cyclosporine on biliary lipids in humans. Changes in
      lipid composition and secretion were correlated with serum cyclosporine levels,
      clinical events, and allograft function. Bile samples were withdrawn via a T-tube
      at interval time points in 17 patients during the first 3 months
      posttransplantation. Total and individual bile acid, cholesterol, and
      phospholipid were determined using high-performance liquid chromatography.
      Biliary lipid profiles were then correlated with clinical events, serum
      cyclosporine levels, and other clinical laboratory values. Biliary lipid
      concentrations decreased in 3 patients during periods of graft dysfunction (acute
      cellular rejection, drug-induced hepatitis, and inferior vena caval thrombosis)
      and increased with resolution of the graft injury. Serum cyclosporine levels were
      positively correlated with total bile acid, cholesterol, and phospholipid
      concentrations in bile. There was no relationship between the composition of
      secreted bile acids and serum cyclosporine levels. Bile acid, cholesterol, and
      phospholipid secretion were not uncoupled in the presence of cyclosporine. We
      concluded that (1) a decrease in biliary lipid concentrations may be an indicator
      of worsened graft function in some allografts; (2) biliary lipid concentrations
      are correlated with increasing cyclosporine levels; and (3) bile acid composition
      is unchanged, and uncoupling of secretion of other biliary lipids is not observed
      in the presence of cyclosporine.

PMID- 9649638
TI  - Risk factors for recurrence of hepatitis C after liver transplantation.
AB  - Recurrent hepatitis C is a frequent complication after liver transplantation for
      hepatitis C virus-related cirrhosis, but risk factors related to its development
      remain ill defined. Twenty-three patients receiving a primary liver graft for
      hepatitis C virus-related cirrhosis and with an assessable biopsy performed at
      least 6 months after liver transplantation were studied retrospectively. The end
      point of this study was to look for risk factors associated with the development
      of histologic hepatitis C in the graft. Thirty-six major variables were studied,
      and those reaching significance by univariate analysis were included in a
      multivariate analysis. Eighteen patients (78%) developed posttransplant hepatitis
      C. On univariate analysis, six variables showed significant predictive value:
      increased immunosuppression for treatment of acute rejection; pretransplant
      hepatocellular carcinoma; cumulative doses of prednisone at 3, 6, and 12 months
      after transplantation; and mean blood trough levels of cyclosporine in the first
      6 months posttransplantation. On multivariate analysis, two variables retained
      independent statistical significance as predictors of hepatitis C recurrence,
      namely receipt of antirejection therapy (P = .0087) and lower mean cyclosporine
      levels in the first 6 months after transplantation (P = .0134). Therefore,
      recurrence of hepatitis C after liver transplantation seems to be at least
      partially related to posttransplantation immunosuppressive therapy.

PMID- 9649639
TI  - An appraisal of percutaneous treatment of liver metastases.
AB  - Percutaneous treatments, such as ethanol injection and radiofrequency, have been
      recently proposed for the treatment of liver metastases. The aim of this study
      was to evaluate the effects of these treatments in a series of 8 patients who
      subsequently underwent liver resection. These patients had been treated with
      percutaneous methods between December 1995 and May 1997. In 6 patients, the
      primary tumor was colonic; in 2 patients, carcinoid; and in 1 patient, ileal
      leiomyosarcoma. The lesions were all initially small in size (1.5 to 3.5 cm),
      single in 7 patients, and multiple in 1 patient with a carcinoid tumor. The
      initial decision for percutaneous treatment had been made on subjective grounds
      by the radiologists who originally saw the patients. The number of percutaneous
      treatment sessions ranged from 2 to 21. In all patients, a progression of the
      disease occurred. Four patients underwent a right hepatectomy; 1 patient, a left
      lobectomy; 2 patients, a segmentectomy; and 1 patient, a wedge resection. There
      was no operative mortality in any of these 8 patients. Two patients presented
      with seeding of the neoplasm on the diaphragm, which was resected. Histologic
      examination of all surgical specimens revealed the presence of vital neoplastic
      tissue; only two specimens of carcinoid tumors showed more than 50% necrosis of
      the nodules treated percutaneously. These results led us to express doubts as to
      the efficacy of percutaneous ablative treatment for liver metastases.

PMID- 9649640
TI  - A prospective, randomized, double-blind trial evaluating the efficacy of
      ursodeoxycholic acid in prevention of liver transplant rejection.
AB  - Acute cellular rejection (ACR) after orthotopic liver transplantation occurs in
      50% to 80% of patients despite the recent advances in immunosuppressive therapy.
      Adjuvant use of ursodeoxycholic acid (UDCA) is theoretically attractive, but
      studies have shown conflicting results. In this randomized, controlled study, we
      evaluated the efficacy of UDCA in reduction of the incidence of ACR. Thirty
      patients were randomized to receive either UDCA (15 mg/kg) or placebo in addition
      to the standard triple-drug regimen; 14 patients received UDCA, and the rest
      received placebo, for 3 to 6 months. The diagnosis of ACR was based on histologic
      criteria. Three patients withdrew from the study within 1 month of therapy, all
      because of capsule size. There was no difference in the total incidence of ACR
      between the placebo and UDCA groups, with 12 and 11 episodes within 6 months,
      respectively; the overall incidence of rejection was 77%. There were also no
      differences in the incidence of recurrent rejection, in the number of rejection
      episodes occurring after 5 days of therapy, or in the use of OKT3. There was no
      difference in 1-year survival between groups. This study shows that adjuvant
      therapy with UDCA in addition to standard triple-drug immunosuppressive therapy
      does not reduce the incidence of ACR.

PMID- 9649641
TI  - The effect of a positive T-lymphocytotoxic crossmatch on hepatic allograft
      survival and rejection.
AB  - The influence of crossmatching in liver transplantation is still controversial,
      and at present, our unit does not alter management according to the result of
      standard lymphocytotoxicity testing. This study retrospectively assessed outcome
      of grafts transplanted in the presence of preformed antidonor cytotoxic antibody.
      One hundred twelve patients undergoing their first orthotopic liver
      transplantation had results available (mean follow-up: 18 months). Twelve
      patients had a positive crossmatch and 100 negative. The 1-year graft survival
      was 58% in the positive crossmatch group, compared with 81% in the negative
      crossmatch group (P = .02). The 1-year patient survival was 83% in the positive
      crossmatch group compared with 90% in the negative group (P = .41). Acute
      cellular rejection occurred in 6 of 7 (86%) grafts surviving more than 7 days in
      the positive crossmatch group compared with 46 of 88 (52%) grafts in the negative
      group (P = .09). However, episodes of further acute cellular rejection requiring
      treatment occurred in 4 of the 6 grafts in the positive crossmatch group but in
      only 4 of the 46 grafts with a negative crossmatch (P = .0006). The authors
      conclude that evidence exists in our population that preformed antidonor
      antibodies adversely affect the outcome of hepatic allografts but not patient
      survival.

PMID- 9649642
TI  - Weight change and obesity after liver transplantation: incidence and risk
      factors.
AB  - Obesity is a concern in the long-term management of patients following liver
      transplantation, yet the risk of obesity and the factors that influence its
      development have not been well defined. We evaluated posttransplantation weight
      change among a cohort of 774 adults who had their height and weight recorded
      before liver transplantation at three major centers. Obesity was defined as a
      body mass index (BMI) of at least 30 kg/m2. Weight at transplantation was
      adjusted by the amount of ascites removed. Mean BMI increased from 24.8 kg/m2
      pretransplantation to 27.0 kg/m2 in the first posttransplantation year, to 28.1
      kg/m2 in the second year, and very little with subsequent observation. Among 320
      patients who were not obese before transplantation, 21.6% became obese within 2
      years after transplantation. On evaluation of numerous potential donor and
      pretransplantation risk factors, greater recipient BMI, greater donor BMI, and
      being married were found to be predictors of subsequent obesity (P < .05).
      Posttransplantation predictors of obesity included absence of acute cellular
      rejection, higher cumulative prednisone dose in the second year, and cyclosporine
      based immunosuppression, although only rejection and prednisone dose remained
      predictors on multivariate analysis. Despite the marked weight gain after
      transplantation, prevalence of obesity at 2 years was only slightly greater than
      in the general US population. Obesity occurred commonly after liver
      transplantation, sometimes with a striking gain in weight. In addition to BMI at
      transplantation, donor BMI, marital status, occurrence of acute rejection, and
      prednisone dose affected the incidence of obesity.

PMID- 9649643
TI  - Intraoperative donor cholangiography.
AB  - Biliary drainage has long been called the Achilles' heel of liver
      transplantation, and biliary complications compromise the success of liver
      transplantation by increasing graft loss and the rates of a required second
      operation, morbidity, and mortality. One cause of complications is unrecognized
      anomalous biliary anatomy. We examined 73 intraoperative donor duct
      cholangiograms (IODDCs) to assess our ability to identify biliary anomalies
      intraoperatively. Normal anatomy was seen in 42% (31/73); some part of the right
      sided biliary system drained into the left bile duct in 22% (16/73); trifurcated
      systems with a single branch point for the right posterior, right anterior, and
      left ducts appeared in 16% (12/73); low insertion of a right segmental duct to
      the hepatic duct was seen in 11% (8/73); and drainage of a right segmental duct
      into the cystic duct or into the hepatic duct at the cystic duct origin was noted
      in 8% (6/73). It was believed that the last group represented a condition that
      dictated extra caution in biliary reconstruction. The incidence of radiographic
      recognition of these anomalies was more than twice the clinical recognition in
      our patient population, implying that many such "problem" ducts usually go
      unrecognized. IODDCs facilitate training of transplant fellows. Costs are low,
      and morbidity is nil.

PMID- 9649644
TI  - Splanchnic hyperemia after liver transplantation in patients with end-stage liver
      disease.
AB  - Systemic and splanchnic hemodynamic parameters were evaluated in 12 patients with
      cirrhosis before and 3 and 6 months after liver transplantation. Results were
      compared with those obtained in 8 healthy subjects. Three months after liver
      transplantation recipients had an increase in mean arterial pressure (98 +/- 7 v
      78 +/- 9 mmHg; P < .05), an insignificant decrease in cardiac index (3. 4 +/- 0.6
      v 4.0 +/- 1.0 L . min-1 . m-2), and a marked increase in peripheral vascular
      resistance (1,563 +/- 308 v 800 +/- 205 dyne . s . cm-5; P < .05) compared with
      pretransplantation values. Portal blood flow was also significantly increased
      (1,494 +/- 200 v 829 +/- 130 mL/min; P < .05). These hemodynamic changes were
      more pronounced 6 months after transplantation (mean arterial pressure, 100 +/- 8
      mmHg; cardiac index, 3.0 +/- 1.0 L . min-1 . m-2; P < .01; peripheral vascular
      resistance, 1,680 +/- 405 dyne . s . cm-5; portal blood flow, 1,520 +/- 180
      mL/min). Systemic hemodynamics 6 months after liver transplantation were similar
      to those observed in the healthy control group (mean arterial pressure, 95 +/- 6
      mmHg; cardiac index, 2.9 +/- 0.9 L . min-1 . m-2; peripheral vascular resistance,
      1,480 +/- 380 dyne . s . cm-5). However, portal blood flow was still
      significantly higher than in healthy controls at 6 months (1,520 +/- 180 v 910 +/
      140 mL/min; P < .05). This study shows that systemic hemodynamics are normalized
      after liver transplantation. However, an increase in portal blood flow occurs and
      persists for at least 6 months after liver transplantation. Further studies are
      needed to clarify the cause of the abnormally high portal flows.

PMID- 9649645
TI  - Cholestatic hepatitis C in liver allografts.
AB  - Some liver allograft recipients with hepatitis C virus (HCV) infection develop
      hyperbilirubinemia, which might be the result of a cholestatic variant of
      hepatitis C. We evaluated all liver biopsy samples from 6 liver transplant
      recipients who had polymerase chain reaction-positive HCV infection and
      histologic evidence of hepatitis and jaundice and compared them with liver biopsy
      samples from a control group of transplant recipients with HCV hepatitis without
      jaundice. Patients with known ductopenic rejection, biliary obstruction, or co
      infection with hepatitis A or B were excluded from the study. Measurement of
      viral titers and genomic typing were performed when possible. Six patients
      developed hepatitis and jaundice, with maximum bilirubin levels ranging from 5.8
      to 47.6 mg/dL. In this group, 5 (83%) had moderate interface hepatitis (control
      group, 15%), 6 (100%) had confluent necrosis (control group, 12%), 5 (83%) had
      bridging fibrosis (control group, 18%), 4 (67%) had significant hepatocyte
      swelling (control group, 9%), 4 (67%) had prominent ductular proliferation
      (control group, 3%), and 6 (100%) had mild duct damage and inflammation (control
      group, 53%). All 6 of the patients with cholestasis had allograft failure. Of
      these, three allografts were available for review, which did not reveal occult
      obstruction, rejection, or duct loss. All patients in the control group have
      retained their allografts. In 4 patients with cholestasis, the median HCV RNA
      titer was 93.97 mEq/mL, with a mean of 54.19 mEq/mL (control mean = 5.2 mEq/mL).
      Five patients also underwent viral genomic typing: 2 with type 1a, 2 with type
      1b, and 1 with mixed type 1a and 1b. Cholestasis in patients with
      posttransplantation hepatitis C may be caused by an aggressive HCV infection that
      exhibits histologic features of confluent necrosis, hepatocyte swelling, and/or
      ductular proliferation. Viral titers are often increased in such patients.

PMID- 9649646
TI  - Bone metabolism in orthotopic liver transplantation: a prospective study.
AB  - Bone mineral density (BMD) and mineral metabolism were assessed in 54 patients
      with end-stage liver disease who were evaluated for orthotopic liver
      transplantation (OLT) and assessed 3, 6, and 12 months after surgery in 26
      patients who underwent OLT. Serum and urinary electrolyte and mineral levels,
      serum liver function test results, and parathyroid hormone (PTH), osteocalcin
      (BGP), 25-hydroxyvitamin D, and urinary hydroxyproline levels were assessed. BMD
      of the lumbar spine was measured at baseline and 3, 6, and 12 months after OLT.
      At baseline, 40.7% of patients had BMD below the fracture threshold (0.800
      g/cm2). Using multiple stepwise regression analysis, we found that BMD was
      significantly (P < .0001) affected by age, serum creatinine level, and PTH level
      but not by indices of cholestasis or liver function. In the patients who
      underwent OLT, a 1.4% reduction (P < .006) was observed in BMD 3 months after
      OLT. Thereafter, BMD returned to pretransplant values. A significant increase in
      serum BGP was observed after 6 (P < .02) and 12 (P < . 005) months. PTH levels
      increased progressively 3 (P < .02), 6 (P < . 001), and 12 (P < .0001) months
      after OLT. This increase did not seem to be caused by cyclosporine-induced
      nephropathy. It was concluded that osteopenia is a major complication in hepatic
      cirrhosis, regardless of its causes. The increase in serum BGP levels 6 and 12
      months after OLT indicates metabolic activation of osteoblasts. The increase in
      PTH levels after OLT warrants further investigation.

PMID- 9649647
TI  - Recurrent hepatitis C virus infection after liver transplantation:
      immunohistochemical assessment of the viral antigen.
AB  - BACKGROUND: The value of immunohistochemical methods to identify hepatitis C
      virus antigen (HCVAg) in liver tissue has not been established. We have evaluated
      the significance of HCVAg expression in livers of patients with transplants and
      recurrent hepatitis C virus (HCV) infection. METHODS: Forty-two liver biopsy
      specimens from 32 liver-transplant recipients with recurrent HCV infection were
      tested for HCVAg using fluorescein isothiocyanate-labeled polyclonal,
      polyreactive human immunoglobulin. Histologic assessment of liver and
      quantitation of HCV RNA in sera were carried out in specimens obtained
      simultaneously with biopsies. RESULTS: HCVAg was found in 33% of the liver
      specimens obtained during the first month after transplantation and in all liver
      specimens obtained between 1 and 18 months after transplantation. Amounts of the
      antigen were significantly greater in specimens obtained more than 1 month after
      transplantation. A statistically significant increase of the average HCV RNA
      level in serum was observed in samples tested after the first month after the
      transplantation, and some decrease in the HCV RNA level was found in those
      obtained between 6 and 18 months after transplantation. Larger amounts of HCVAg
      were observed in specimens corresponding to episodes of acute or chronic
      hepatitis than in those associated with minimal parenchymal evidence of
      rejection. CONCLUSIONS: OBSERVATIONS of HCVAg expression in liver biopsy
      specimens indicated that the presence of viral antigens in hepatocytes is a
      constant finding in specimens obtained 1 month or longer after transplantation.
      Although large amounts of HCVAg correlated with acute or chronic hepatitis, the
      nature of this association with the development of pathologic changes remains to
      be established.

PMID- 9649648
TI  - Late hypertension after liver transplantation: a comparison of cyclosporine and
      tacrolimus (FK 506).
AB  - Hypertension frequently develops early after liver transplantation when
      cyclosporine-based immunosuppression is used. However, initial experience with
      tacrolimus has suggested that its use leads to a lower early incidence of
      hypertension. In this study, the blood pressure status of patients treated with
      cyclosporine (n = 131) and those treated with tacrolimus (n = 28) was compared 24
      months after liver transplantation. At this time interval, the prevalence of
      hypertension in the cyclosporine and tacrolimus groups were 82% and 64%,
      respectively (P < .05). For those patients who were hypertensive by 24 months,
      onset was delayed in the tacrolimus group compared with the cyclosporine group:
      40% versus 71% and 73% versus 93% at 1 and 12 months, respectively (P < .05).
      Within the cyclosporine group, patients with hypertension were heavier than those
      with normal blood pressure, 84.7 +/- 1.8 versus 73.4 +/- 4.0 kg, respectively (P
      < .05). Within the tacrolimus group, hypertensive patients had lower glomerular
      filtration rates and higher renal vascular resistances compared with normotensive
      patients, 74 +/- 12 versus 47 +/- 6 mL/min and 15,711 +/- 2,445 versus 28,830 +/-
      4,310 dyne/s/cm5/m2, respectively (P < .05). There were no within-group
      differences for age, gender, pretransplant history of hypertension, family
      history of hypertension, graft function, or daily doses of prednisone,
      cyclosporine, or tacrolimus. These results indicate that, compared with
      cyclosporine, the onset of hypertension after liver transplantation is delayed
      and less prevalent with tacrolimus. Additionally, hypertension is associated with
      increased body weight in cyclosporine-treated patients and with more severe renal
      dysfunction in patients receiving tacrolimus. The relationships of these findings
      to the development of posttransplant hypertension requires further study.

PMID- 9649649
TI  - Tolerance induction using bone marrow transplantation.

PMID- 9649650
TI  - Stress echocardiography identifies coronary artery disease in liver transplant
      candidates.

PMID- 9649651
TI  - Announcements 
AB  - Copyright

PMID- 9649652
TI  - Schnitzler's syndrome versus adult onset Still's disease.
AB  - We report the case of a 50-year-old man with a 4-year history of high spiking
      fever accompanied by a widespread, urticarial, non-pruritic or only sometimes
      mildly pruritic eruption and arthralgia. He also had generalized lymphadenopathy,
      hepatosplenomegaly, and hyperosteoses of the lower lumbar spine. Laboratory
      examination revealed an elevated erythrocyte sedimentation rate, elevated white
      blood cell and platelet counts, hypoalbuminemia, and elevated serum IgM with IgM
      kappa monoclonal immunoglobulin. We diagnosed his condition as Schnitzler's
      syndrome, in contrast to the diagnosis of adult onset Still's disease, for which
      he had been initially followed up by his internist. We compare clinical and
      histopathological findings for both diseases and, as this patient meets two of
      the six existing diagnostic criteria for adult onset Still's disease, we propose
      that Schnitzler's syndrome is an important entity to be added to the list of
      differential diagnoses for adult onset Still's disease.

PMID- 9649653
TI  - Pemphigus vulgaris on an old surgical scar: Koebner's phenomenon?
AB  - Pemphigus is an autoimmune bullous skin disorder. Several cases have been
      reported to originate in traumatized areas or on a scar, suggesting Koebner's
      phenomenon. Pemphigus can either remain localized or subsequently extend. This
      paper reports on a 60-year-old man in whom pemphigus vulgaris began on a 40-year
      old surgical scar. The pemphigus initially remained localized to the scar and
      subsequently extended after two months. The time to onset of this bullous disease
      on the scar was especially long, compared to that which has been previously
      reported in the literature. A few cases have been reported where pemphigus
      developed a few months to a few years after surgery. A time to onset exceeding 3
      years is extremely rare.

PMID- 9649654
TI  - The use of skin substrates deficient in basement membrane molecules for the
      diagnosis of subepidermal autoimmune bullous disease.
AB  - A case is presented of subepidermal, autoimmune bullous disease in which the
      initial examinations suggested the combination of epidermolysis bullosa acquisita
      and bullous pemphigoid. The diagnosis of epidermolysis bullosa acquisita was made
      by indirect immunofluorescence microscopy: the patient's serum bound to normal
      skin substrate but not to type VII collagen-deficient skin substrate derived from
      a patient with mutilating dystrophic epidermolysis bullosa. The use of skin
      substrates deficient in basement membrane molecules also excluded the presence of
      concomitant, circulating bullous pemphigoid autoantibodies in our patient. The
      diagnosis of epidermolysis bullosa acquisita was confirmed by split mapping,
      fluorescence overlay antigen mapping and Western blot.

PMID- 9649655
TI  - Linear IgA disease and ulcerative colitis.
AB  - Linear IgA disease is an acquired bullous disease of the skin characterized by
      linear IgA deposits along the dermal-epidermal junction. Inflammatory bowel
      diseases have been rarely reported in association with linear IgA disease. We
      have recently observed a patient suffering from ulcerative colitis who developed
      a cutaneous bullous eruption that was diagnosed as a linear IgA disease. Foreign
      antigens penetrating the inflamed bowel mucosa might give rise to the production
      of autoantibodies cross-reacting with the cutaneous antigens involved in the
      pathogenesis of linear IgA disease.

PMID- 9649656
TI  - Crohn's disease masquerading as aphthous ulcers.
AB  - Although intraoral involvement in Crohn's disease (CD) is observed in only
      approximately 9% of cases, oral inflammation precedes intestinal symptoms of CD
      in about 60% of these patients. We describe a 20-year-old male with recurrent,
      painful, intraoral lesions who presented no other signs of systemic disease apart
      from severe loss of body weight. From the routinely screened serological
      parameters only the erythrocyte sedimentation rate and the acute phase reactants
      were elevated. A biopsy from the vestibular mucosa revealed a dense mononuclear
      infiltrate and, focally, small noncaseating granulomas suggestive of CD.
      Gastrointestinal endoscopy was performed showing mucosal involvement reaching
      from the esophagus to the descending colon. The diagnosis of active CD was
      confirmed by histopathology of intestinal biopsy specimens. As oral lesions are
      sometimes treated without a definite diagnosis, we emphasize the need to search
      for underlying systemic illness in the differential diagnosis of recurrent
      inflammatory lesions of the oral cavity.

PMID- 9649657
TI  - Production of host-protective (IFN-gamma), host-impairing (IL-10, IL-13) and
      inflammatory (TNF-alpha) cytokines by PBMC from leprosy patients stimulated with
      mycobacterial antigens.
AB  - The production of IFNgamma, IL-10, IL-13 and TNFalpha was determined using PBMC
      from 7 tuberculoid (TT) and 7 lepromatous leprosy (LL) patients, after
      stimulation with several mycobacterial antigens, in an attempt to characterize
      the cytokine responses to these antigens. The results showed that TT patients
      displayed higher IFNgamma levels than LL patients with the mycobacterial antigens
      tested, but no differences in IL-10 production were observed between the two
      groups. MLSC antigen was associated with the lowest IFNgamma production in TT and
      LL groups. Only BCG could be identified with stimulation of IFNgamma production
      in some LL patients. The mycobacterial antigens SP+, SP- and BCG were associated
      with higher TNFalpha production in patients and controls, suggesting that these
      antigens could be involved in immunopathological effects. Our findings showed
      that the antigens tested were associated with a heterogeneous cytokine production
      in leprosy patients. Further studies are required to establish if an individual
      antigen can be identified as inducing a protective immune response in leprosy.

PMID- 9649658
TI  - Drug eruption due to Bufferin showing erythema exsudativum multiforme with a
      photo-recall-like phenomenon.
AB  - A 21-year-old woman who had been taking several kinds of analgesics to treat
      dysmenorrhea developed episodic attacks of a purpuric macular eruption and a
      burning sensation on unexposed areas of the upper chest and back where she had
      sustained severe sunburn eight months earlier. Target-like lesions developed on
      these areas after intake of Bufferin, a combination of aspirin and dialuminate.
      After the eruptions had abated following systemic administration of a
      corticosteroid agent, a challenge test was performed, using a quarter of a tablet
      of Bufferin. The patient developed a temporary burning sensation and a
      erythematous color on the previously sunburned skin. We diagnosed this case as a
      drug eruption due to Bufferin showing erythema exsudativium multiforme with a
      photo-recall-like phenomenon. In our case, skin tests would be useful to confirm
      the causal drug.

PMID- 9649659
TI  - Expression of cathepsins in dermal fibrous tumors: an immunohistochemical study.
AB  - Cathepsins are lysosomal proteases that are distributed in many normal tissues
      and are primarily responsible for intracellular catabolism and turnover. The
      increased level of cathepsins in tumors together with their ability to degrade
      extracellular matrix proteins has led to the hypothesis that they are involved in
      the process of invasion and metastasis. We studied immunohistochemically the
      expression of cathepsins B, pro-D and pro-L in 8 cases of dermatofibrosarcoma
      protuberans (DFS), five cases of atypical fibroxanthoma (AFX) and twenty cases of
      dermatofibroma (DF). Expression of cathepsins B and pro-D could be detected in 5
      of the 8 cases (62.5%) of DFS, whereas cathepsin pro-L was found in 4 (50%)
      cases. All AFX expressed cathepsin pro-L, whereas cathepsins B and pro-D were
      observed in 4 out of 5 cases. None of the malignant tumors showed a recurrence or
      metastasis after a period of four years. We found no expression of cathepsins in
      DF. In the epidermis and appendages, an expression of cathepsins pro-D, pro-L and
      B was seen. We conclude that cathepsins may be markers of increased metabolism
      rather than specific markers of malignancy.

PMID- 9649660
TI  - A comparison of the efficacy and safety of lymecycline and minocycline in
      patients with moderately severe acne vulgaris.
AB  - A multicentre, randomised, double-blind and double-dummy study was conducted to
      compare the efficacy and safety of lymecycline (n = 71) with that of minocycline
      (n = 73) in 144 patients with moderately severe acne vulgaris. Patients with an
      acne score of 1-5 on the Leeds scale received oral lymecycline, 300 mg/day for 2
      weeks, then 150 mg/day for 10 weeks or oral minocycline, 100 mg/day for 2 weeks
      then 100 mg every other day for 10 weeks. Inflammatory, non-inflammatory and
      total lesion counts were determined at baseline (week 0) and after 4, 8 and 12
      weeks' treatment, and global efficacy and safety assessments were made by the
      patient and investigator at the end of the study. Both treatments were equally
      effective at reducing differential lesion counts and improving acne condition and
      severity, with no significant differences between treatments. Inflammatory
      lesions were reduced by 50.6% and 52.2% with lymecycline and minocycline,
      respectively, and non-inflammatory lesions by 40.6% and 32.2%. Acne severity was
      reduced by 42.4% with lymecycline and by 47.9% with minocycline. A total of 4.3%
      of lymecycline recipients and 4.1% of minocycline recipients experienced
      treatment-related adverse events, the majority of which were mild in nature.
      Lymecycline was as effective as minocycline for the treatment of moderately
      severe acne vulgaris. Both treatments were well tolerated, although there were
      slightly fewer adverse gastrointestinal and dermatological effects with
      lymecycline.

PMID- 9649661
TI  - Regulatory effects of 1alpha,25-dihydroxyvitamin D3 on inflammatory responses in
      psoriasis.
AB  - Topical application of 1alpha,25-dihydroxyvitamin D3 (VD3) is thought to be
      beneficial in psoriasis because of its action in regulating keratinocyte
      proliferation and inflammation mediated by various cytokines. We assessed the
      effect of VD3 on the production levels of interferon (IFN)-alpha, interleukin
      (IL)-6, IL-8 and tumor necrosis factor (TNF)-alpha in mitogen-stimulated
      peripheral blood mononuclear cells (PBMC) of psoriatic patients. The results
      demonstrated that VD3 significantly inhibited IFN- , IL-6, and IL-8 levels
      produced by concanavalin A (Con A)-stimulated PBMC of psoriatic patients in a
      dose-dependent manner, and reduced mRNA expression for IFN- and IL-8. These
      findings suggest that in addition to the direct anti-proliferation effect on
      keratinocytes, VD3 may down-regulate the inflammatory cytokine production by
      infiltrating cells in psoriatic lesions.

PMID- 9649662
TI  - Multiple squamous cell carcinomas of the skin during long-term treatment with
      hydroxyurea.
AB  - Hydroxyurea is a chemotherapeutic agent used extensively for myeloproliferative
      disorders. Cutaneous side effects have been described during long-term
      hydroxyurea treatment. We described the occurrence of multiple squamous cell skin
      carcinomas in a patient treated with hydroxyurea for chronic myelogenous
      leukemia. The lesions were removed and the hematological therapy switched to
      busulfan. In a previously reported case, the development of cutaneous epithelial
      cancers required the discontinuation of hydroxyurea, in addition to the surgical
      excision of the neoplastic lesions. Since squamous cell carcinoma is a malignant
      cutaneous neoplasm that can metastatize, the surveillance of skin changes is
      advisable during hydroxyurea treatment.

PMID- 9649663
TI  - Is chronic ulcerative stomatitis an entity? Clinical and immunological findings
      in 18 cases.
AB  - Chronic ulcerative stomatitis (CUS), a rare disease of oral mucosa found to be
      associated with unusual antinuclear antibodies reactive exclusively with squamous
      epithelia (squamous epithelium-specific antinuclear antibodies - SES-ANA), has
      been reported to occur almost exclusively in older females and to respond
      dramatically to antimalarials. We report on a large series of 18 cases positive
      for SES-ANA, 15 of them with active CUS, followed-up for several years. We found
      that the disease may occur, although rarely, in men and younger females. The
      antibodies persist after clearance of mucosal lesions, are fixed in vivo and also
      in uninvolved skin and other mucosa, and may occur in patients without CUS. Thus
      their pathogenic potential remains to be established. We also describe some
      unusual cases of CUS, one associated with cicatricial conjunctivitis, another
      associated with gluten-sensitive enteropathy and bizarre skin lesions, and 3
      cases associated with lichen planus (LP) or LP-like lesions. The antimalarials,
      initially highly effective, even for several months or years, not infrequently
      proved to be insufficient and the relapses responded usually only to combined
      therapy with chloroquine and small doses of corticosteroids. SES-ANA antibodies
      are quite specific and present an immunologic marker of this unusual autoimmune
      disease.

PMID- 9649664
TI  - Sweet's syndrome associated with cutaneous T cell lymphoma.
AB  - Although the association of Sweet's syndrome with haemoproliferative disorders or
      solid malignant tumors is well known, only two previous observations associated
      with T lymphoma have been reported. We report the first observation of Sweet's
      syndrome associated with cutaneous T cell lymphoma. The role of a cytokine
      cascade released by an abnormal T cell clone is discussed as an initiating event
      responsible for secondary infiltration with neutrophils.

PMID- 9649665
TI  - Behcet's disease-like symptoms induced by the Herpes simplex virus in ICR mice.
AB  - Herpes simplex virus (HSV) infection has been suggested to be one of the
      etiologic or triggering factors in Behcet's disease. To test this hypothesis, 258
      ICR mice were inoculated with HSV type 1 (KOS strain). After the induced
      infection, 86 mice (33.3%) died, 77 (29. 8%) showed Behcet's disease-like
      symptoms, and 95 (36.8%) had a healthy, normal appearance or just a single
      symptom. The symptoms included skin ulcers on the earlobe, neck, abdomen, back or
      face (57. 1%); eye syndromes (39.0%); partial hair loss (33.8%); genital ulcers
      (19.5%); bullae (11.7%); arthritis (5.2%); gastrointestinal ulcer (5.2%); and
      tongue ulcers (3.9%). The induced Behcet's disease-like symptoms are similar to
      the clinical manifestations of ulcers, uveitis, and arthritis which have been
      significant in diagnosing Behcet's disease in patients.

PMID- 9649666
TI  - Recurring atypical ("pseudosarcomatous") cutaneous fibrous histiocytoma.
AB  - Atypical ("pseudosarcomatous"), cutaneous, fibrous histiocytoma is a rare
      connective tissue tumor arising on the trunk and limbs in young adults. Its
      histological diagnosis is difficult. We report the case of a 25-year-old woman
      who presented a nodule on her left leg. Two years after an incomplete excision,
      she developed a large local recurrence. Additional radiotherapy, after total
      reexcision was performed. This treatment was successful and no further recurrence
      occurred. Clinicopathological features of atypical ("pseudosarcomatous"),
      cutaneous, fibrous histiocytoma are reviewed. Differential diagnoses, including
      atypical fibroxanthoma, angiomatoid fibrous malignant histiocytoma and aneurysmal
      fibrous histiocytoma are discussed.

PMID- 9649667
TI  - Introduction to the round table: "UV and the immune system" 

PMID- 9649668
TI  - Immunosuppression induced by chronic ultraviolet irradiation in humans and its
      prevention by sunscreens.

PMID- 9649669
TI  - Successful treatment of Grover's disease with calcipotriol.
AB  - We report the case of an 84-year-old man with clinical, histological and electron
      microscopic features of a Darier-like pattern of Grover's disease. The lesions
      had a persistent course, with a 5-month history before diagnosis and a clinical
      onset 2 years after the surgical removal of a cholangiocarcinoma. A significant
      clinical improvement was observed after a three-week course of calcipotriol
      ointment applied as a monotherapy regimen. Clinical uses of topical calcipotriol
      in dermatological conditions are reviewed with emphasis on dyskeratotic
      disorders.

PMID- 9649671
TI  - Surgery and cyclosporine A in the treatment of erosive lichen planus of the feet.
AB  - Erosive lichen planus is known to be relatively unresponsive to medical
      treatment. Surgery could be an alternative treatment for this disease. We report
      the case of a 68-year-old man with a 10-year history of painful, disabling,
      ulcerative lesions on the soles of both feet. All previous topical and oral
      treatments had failed and his condition was gradually worsening. Cyclosporine A
      was administered twice. The first time, systemic cyclosporine A gave a marked but
      only temporary improvement. The second time, treatment with cyclosporine A was
      begun 10 days before the ulcer on his left sole was covered with a Thiersch split
      skin graft. The grafting was successful, so cyclosporine A was gradually reduced
      to smaller maintenance doses and 10 months later it was completely withdrawn. The
      patient refused to undergo surgery on his right foot thus providing the
      opportunity to compare the results. At the present time, eighteen months
      following grafting and ten months after total withdrawal of cyclosporine A, the
      condition of the left sole is stable and free from pain while the ungrafted ulcer
      on his right sole is still painful and has increased in size.

PMID- 9649670
TI  - Verrucous cyst.
AB  - A verrucous cyst is an unusual, histopathologically distinctive, epidermoid cyst
      characterised by verrucous changes in its wall. We report two cases of verrucous
      cysts in different patients, one on the back and the other on the cheek.
      Clinically, the lesions were thought to represent an epidermoid cyst and a basal
      cell carcinoma, respectively. Histologically, we found in both cases an
      intradermal epidermoid cyst lined by a stratified squamous epithelium with focal
      cytopathogenic viral changes, consisting of papillomatosis, ortho- and
      parakeratosis, and hypergranulosis. One case also showed, within the squamous
      areas of the hyperplastic epithelium, occasional squamous eddies. These
      histopathological features support the diagnosis of verrucous cyst, which may
      represent a manifestation of human papillomavirus infection. This virus may
      induce cyst formation or just infect a pre-existing one.

PMID- 9649672
TI  - Dose-responses for UV-induced suppression of various immune responses.

PMID- 9649673
TI  - Rheumatoid vasculitis in a patient with seronegative rheumatoid arthritis.
AB  - We report on a 47-year-old woman with a 10-year history of seronegative
      rheumatoid arthritis (RA) who had experienced an episode of bilateral aseptic
      pleuritis, and in whom livedo reticularis and ulcers had developed on both lower
      extremities. Histological examination revealed rheumatoid vasculitis. In
      rheumatoid vasculitis, high titers of rheumatoid factors are commonly observed.
      In our case, however, there have been no characteristic laboratory findings
      throughout the course of the disease so far, despite the active RA. This report
      describes a rare case of seronegative RA with systemic rheumatoid vasculitis.

PMID- 9649674
TI  - Epidemiology of contact dermatitis. The information network of departments of
      dermatology (IVDK) in Germany.
AB  - In 1988, the multicenter project "Information Network of Departments of
      Dermatology (IVDK)", including eight university skin hospitals was founded. It
      now comprises 30 participating centers. At these centers, all patch test results
      are recorded, together with important anamnestic details and, twice a year, these
      are sent to the data center at the Gottingen University Skin Hospital. Regular,
      descriptive analyses of data collected by this epidemiological surveillance
      system serve the different purposes discussed in this paper: 1) observation of
      "sentinel events"; e.g. an increase in the proportion of patients tested who were
      sensitized to a certain allergen, or the identification of certain subgroups at
      particular risk as a starting point for further research or preventive action,
      and 2) advancement of good clinical practice in patch testing. In October 1996, a
      working group of the European Society of Contact Dermatitis (ESCD) called the
      "European Surveillance System on Contact Allergies (ESSCA)" was established with
      a similar aim of communal data collection and analysis.

PMID- 9649675
TI  - Transient leucoderma appearing in an untreated area following contact
      immunotherapy for alopecia areata.
AB  - One of the possible unwanted side effects following contact immunotherapy of
      alopecia areata is skin hypopigmentation, either in the form of a transient, post
      inflammatory hypopigmentation or as the development of a persistent, depigmented
      patch. A case of leucoderma occurring on the forehead of a 16-year-old girl
      following application of squaric acid dibutylester to the scalp for the treatment
      of alopecia areata is described. Past medical and family history were negative
      for vitiligo and autoimmune disorders. The hypopigmented patch was distant from
      the scalp area where squaric acid dibutylester had been applied, and it was not
      preceded by any sign of eczema, erythema or itch in the same area. Moreover, it
      faded as soon as treatment was discontinued. A 4-year follow-up revealed no
      evidence of vitiligo. In conclusion, the possible occurrence of a transient
      leucoderma in untreated areas should be included among the side effects of
      contact immunotherapy of alopecia areata with squaric acid dibutylester.

PMID- 9649676
TI  - Longterm remission of tumor-stage mycosis fungoides following total-skin electron
      beam radiotherapy.
AB  - We report the case of a patient with mycosis fungoides, stage II B with
      generalized plaques and ulcerated tumors in a severely reduced general condition,
      with anemia and extremely poor compliance, who was successfully treated with
      total-skin electron-beam radiotherapy with a less severe relapse after more than
      three years.

PMID- 9649677
TI  - Coagulation factor XIII in scleroderma.
AB  - The ability of blood coagulation factor XIII (FXIII) to affect collagen synthesis
      and degradation led to its use in the treatment of scleroderma. Encouraging
      initial results were achieved principally in terms of skin sclerosis,
      musculoskeletal involvement and weakness. Further assessment of this treatment in
      scleroderma was abandoned when, following the HIV epidemic, FXIII use became
      strictly regulated. Safer concentrates are now available which may allow us to
      reconsider this therapy. This paper, which briefly reviews available data related
      to FXIII use in scleroderma and which proposes general rules for prescribing, is
      aimed at generating an open debate as to the need to widen the regulated use of
      FXIII to scleroderma.

PMID- 9649678
TI  - Adhesion molecule expression in basal cell carcinoma.
AB  - Basal cell carcinomas (BCCs) are frequently associated with a peritumoral
      mononuclear infiltrate. Until now, the function of this inflammatory infiltrate
      and its possible role in the control of tumor growth is unclear. Mechanisms
      controlling endothelial and target cell adhesiveness for leukocytes are important
      features in the development of a specific local immune response. The expression
      and distribution of the adhesion molecules ICAM-1, VCAM-1 and E-selectin by
      microvascular endothelial cells and tumor cells, together with their leukocyte
      receptors LFA-1, VLA-4 and CLA respectively, were studied in 33 BCCs of different
      histological subtypes. In normal skin, ICAM-1 is expressed by resting endothelial
      cells, whereas VCAM-1 and E-selectin expression correlates with endothelial
      activation. The epidermis in normal conditions displays no ICAM-1, VCAM-1, or E
      selectin expression. In BCC, endothelial ICAM-1 expression was only slightly
      increased compared to normal skin, whereas expression of endothelial VCAM-1 and E
      selectin was low or absent in all BCCs examined. Peritumoral infiltrates
      contained mostly LFA-1-expressing lymphocytes, with minimal VLA-4 and CLA
      positivity. In none of the cases studied was adhesion molecule expression by BCC
      tumor cells identified. The lack of significant expression of adhesion molecules
      on peritumoral vascular endothelial cells and BCC tumor cells does not support
      the idea of specific, cell-mediated immunity being an important mechanism in
      limiting BCC tumor spread.

PMID- 9649679
TI  - Shaving: a simple and effective treatment for moderate congenital hypertrichosis.
AB  - Congenital hypertrichosis is a rare disorder. It is sometimes associated with
      facial dysmorphism, and dental and gingival abnormalities. This condition
      constitutes an esthetic problem and regular shaving with a simple razor can be a
      simple method of treatment.

PMID- 9649680
TI  - Pachyonychia congenita with steatocystoma multiplex. A report of two cases and a
      discussion of the classification.
AB  - Pachyonychia congenita is a rare syndrome in which the main and most common
      clinical sign is onychodystrophy of all finger and toe nails. The most frequent
      type of transmission seems to be autosomal dominant, but recessive forms have
      also been described. Typical onychodystrophy can be associated with other
      clinical manifestations. The most recent literature refers to descriptions of
      about 250 cases up until 1993. Numerous classifications of pachyonychia congenita
      have been suggested by several authors over the years. We report two cases of
      pachyonychia congenita in association with steatocystoma multiplex in a mother
      and son.

PMID- 9649681
TI  - Purpuric lichen nitidus.
AB  - We report the case of a patient in whom lichen nitidus with hemorrhage was found
      on the palm and the thigh. Histopathologically, the small vessels in the lesions
      showed extensive changes and were increased in number. The capillary walls
      revealed degenerative changes with extravasation of erythrocytes. On electron
      microscopy, amorphous, electron-dense deposits were observed along the outside of
      the endothelial cells. These findings can explain the presence of the hemorrhagic
      changes. We describe this as a case of purpuric lichen nitidus.

PMID- 9649682
TI  - Expression of the bcl-2 homologue bax in normal human skin, psoriasis vulgaris
      and non-melanoma skin cancers.
AB  - Bax (bcl-2-associated X protein) is a recently identified member of the bcl-2
      family and one of the principal inducers of apoptosis. We examined the
      distribution of bax protein in normal human skin and several skin diseases by
      immunohistochemistry. Bax immunoreactivity was present in normal epidermis and
      its appendages, with the suprabasal compartment being stained more strongly than
      basal keratinocytes. Bax immunostaining was also detected in the epidermis of
      psoriasis vulgaris and 5 keratoacanthomas examined. We could observe only weak
      bax immunoreactivity in 15 squamous cell carcinomas examined, with the exception
      of well-differentiated tumour islands in two tumours, which expressed
      immunostaining for bax comparable to that of normal suprabasal epidermis.
      Immunostaining for bax was negative in 12 out of 17 basal cell carcinomas and the
      remaining five tumours showed weak bax reactivity in tumour cells scattered
      within tumour masses and in palisading layers of some tumour formations. Western
      blot analysis confirmed the expression of bax protein in normal skin, psoriasis
      vulgaris and squamous cell carcinoma as well as the absence of bax in basal cell
      carcinoma. Our findings suggest that the loss of pro-apoptotic bax protein in
      basal cell carcinoma and its reduced expression in squamous cell carcinoma might
      be an important step in the development of these two skin cancers.

PMID- 9649683
TI  - Development of pemphigus foliaceus in a patient with psoriasis: a simple
      coincidence?
AB  - Several cases of psoriasis associated with bullous diseases have been reported in
      the literature. Bullous pemphigoid is the most frequent association observed,
      while pemphigus-related disorders are less frequently described. The authors
      report a case of a patient with long-standing psoriasis who developed pemphigus
      foliaceous and discuss the possible relationship between the diseases.

PMID- 9649684
TI  - Mechanisms of UV-induced immunosuppression. Link between UV-induced tolerance and
      apoptosis.

PMID- 9649685
TI  - Ultraviolet A radiation-induced immunomodulation: molecular and photobiological
      mechanims.

PMID- 9649686
TI  - Post-kala-azar dermal leishmaniasis.
AB  - Post-kala-azar dermal leishmaniasis is a dermatosis which was described during
      the first quarter of this century. Most cases reported are from the Indian
      subcontinent and certain parts of Africa. The disease generally follows an attack
      of kala-azar, usually a few months to several years after the visceral disease
      has healed. The clinical picture is variable. In this report, we present a case
      of post-kala-azar dermal leishmaniasis in a 5-year-old Iranian boy who presented
      with multiple, asymptomatic, erythematous papules on his trunk and extremities
      and a brownish, figurate discoloration on his lower extremities, 4 years after an
      attack of kala-azar which was completely cured. Histopathological examination of
      one of the biopsied papules revealed multiple Leishman bodies. The patient was
      successfully treated with a pentavalent antimonial compound.

PMID- 9649687
TI  - The antipsoriatic dimethyl-fumarate suppresses interferon-gamma -induced ICAM-1
      and HLA-DR expression on hyperproliferative keratinocytes. Quantification by a
      culture plate-directed APAAP-ELISA technique.
AB  - The derivatives of fumaric acid show antipsoriatic effects but details of the
      mechanism of action are largely unknown. The study focused on the effect of
      fumaric acid, dimethyl-fumarate, Zn-, Ca- and Mg-monoethyl-fumarate on the
      interferon-gamma (IFN-gamma)-induced expression of ICAM-1 and HLA-DR molecules on
      keratinocytes. Human hyperproliferative keratinocytes of the HaCaT cell line were
      exposed to IFN-gamma (10 U/ml) alone or in combination with fumaric acid and its
      derivatives for 48 hrs. The effect of fumarates was investigated
      semiquantitatively using the alkaline phosphatase-anti-alkaline phosphatase
      (APAAP) method. Subsequently, the effect of dimethyl-fumarate, the main component
      of "fumaric acid therapy", was evaluated quantitatively by means of an APAAP
      ELISA technique. The semiquantitative evaluation revealed that in the micromolar
      dose range investigated only dimethyl-fumarate demonstrated substantial growth
      inhibition and down-regulation of the cell surface markers. In the quantitative
      evaluation, dimethyl-fumarate significantly (p</=0.05) suppressed the expression
      of ICAM-1 (84%) and HLA-DR (67%) on HaCaT keratinocytes at a subtoxic
      concentration of 4.0 microM as compared to untreated controls (100%). In
      contrast, concentrations of 4.0, 12 and 35 microM dimethyl-fumarate had no
      influence on the ICAM-1 and HLA-DR expression on IFN-gamma-exposed normal human
      epidermal keratinocytes in primary cultures. Thus, there is experimental evidence
      that dimethyl-fumarate may exert its antipsoriatic effect not only as an
      antiproliferative agent but also by down-regulation of ICAM-1 and HLA-DR
      molecules on hyperproliferative keratinocytes.

PMID- 9649688
TI  - Multiple basal cell carcinoma developing two years after 60Co irradiation.
AB  - A 66-year-old Japanese man developed multiple basal cell carcinoma 2 years after
      receiving 60Co irradiation for oropharyngeal tumors. All of the tumors were
      located within the radiation fields where the skin was atrophied and
      telangiectatic. In the present case, the total dose (112 Gy) of 60Co radiation
      received by the patient had been large and the latent period was much shorter
      than in previously reported cases. It is suggested that the reasons for the short
      latency in our case were 1) the total radiation dose and 2) the fact that the
      area irradiated was a frequently sun-exposed area.

PMID- 9649689
TI  - 99mTc-MIBI uptake in a primitive leptomeningeal melanoma.
AB  - Primitive leptomeningeal melanoma is a rare and aggressive condition. The authors
      report on a case of primitive leptomeningeal melanoma imaged with 99mTc-Sestamibi
      (MIBI). There was an intense accumulation of the radiotracer in the frontal and
      parietal leptomeningeal regions and even after injections of gadolinium the MRI
      continued to reveal a cystic image of the brain. In view of the diagnosis, MRI
      demonstrated only limited usefulness. On the other hand, this case highlights the
      important role of MIBI for the imaging of malignant tumors.

PMID- 9649690
TI  - Acne-like eruption induced by pseudoxanthoma elasticum: effectiveness of liquid
      nitrogen cryotherapy.
AB  - We report a case of pseudoxanthoma elasticum associated with an acneiform
      eruption involving the cervical area. When she was 16 years-old our patient was
      diagnosed with pseudoxanthoma elasticum, affecting the skin (flexural, cervical
      and neck areas) and the eyes (bilateral ocular angioid streaks). Ten years later,
      acneiform lesions (inflammatory and comedones) developed on these lesions: - the
      inflammatory lesions were characterized by phagocytosis of pathological elastic
      fibers inducing granuloma - the histological aspects of pseudoxanthoma elasticum
      were observed around large comedones. This association is rarely reported and we
      think that atypical, cervical acneiform lesions may be an indication of
      pseudoxanthoma elasticum. The mechanism for this association is not clearly
      understood. In our case, Von-Kossa staining was negative for the granulomatous
      lesions and positive for the comedones: calcification could protect elastopathic
      fibers from phagocytosis. Treatment is difficult: anti-acneic treatments are not
      effective except for tetracylines, the anti-inflammatory effects of which can
      improve granulomatous lesions. As its efficacy has been reported in elastosis
      perforans serpiginosa, we used liquid nitrogen cryotherapy on the inflammatory
      lesions with good results (separation of epidermis from dermis perhaps promoting
      transepithelial elimination of the abnormal dermal elastic tissue).

PMID- 9649691
TI  - Are local and systemic conditions important for the development of onychomycosis?
AB  - Available epidemiological data indicate that the prevalence of onychomycosis due
      to dermatophytes increases with ageing. The aim of this study was to investigate
      the epidemiology of dermatophyte nail infections in 2 populations selected only
      on an age basis and to verify whether the presence of onychomycosis was
      associated with increased exposure to possible predisposing factors. From January
      to June 1995, the nails of 1,800 military recruits and 253 elderly individuals
      living in a nursing home were examined. Mycological studies were performed in all
      cases of suspected onychomycosis. The presence of systemic or local diseases that
      may favor fungal nail infection as well as exposure to environmental factors were
      assessed in the 2 populations. Onychomycosis was diagnosed in 8 recruits (0. 44%)
      and 38 of the elderly people (15%). The presence of onychomycosis was not related
      to the degree of exposure to environmental factors or to systemic or local
      diseases.

PMID- 9649692
TI  - Angiolymphoid hyperplasia with eosinophilia.
AB  - We report a case of angiolymphoid hyperplasia with eosinophilia (ALHE).
      Histologically, some vessels were lined with plump endothelial cells.
      Infiltration by lymphocytes, histiocytes and eosinophils was marked. An
      arteriovenous malformation and vessels occluded by endothelial cell hyperplasia
      were present. PCNA staining gave positive results for the nuclei of many of the
      plump endothelial cells. Electron-microscopic findings disclosed increased
      metabolic activity in the cells. These observations suggest that the plump
      endothelial cells, characteristic of ALHE, have high metabolic activity. These
      results suggest that blood flow is increased by arteriovenous malformations and
      that blood pressure is elevated by occlusion, resulting in hyperplasia of plump
      endothelial cells and accelerated neovascularization.

PMID- 9649694
TI  - Analysis of T cell receptor Vbeta repertoires of annular erythema associated with
      Sjogren's syndrome.
AB  - Sjogren's syndrome (SjS) is an autoimmune disorder characterized by lymphocytic
      infiltration into the lacrimal and salivary glands. Annular erythema has recently
      been reported to be a specific, cutaneous manifestation associated with SjS. In
      this study, the T cell receptor (TCR) Vbeta gene usage and expansion was examined
      in annular erythema associated with SjS (AESjS) in 7 patients with primary SjS (5
      definite and 2 probable), using reverse transcriptase polymerase chain reaction
      (RT-PCR) amplification of 22 Vbeta gene families. For 4 out of the 7 patients,
      the TCR V repertoire in lesional skin of AESjS was compared with paired
      peripheral blood mononuclear cells (PBL). In one case, two lesional tissue
      specimens biopsied from different sites of AESjS (face and trunk) were examined.
      As a control, the TCR Vbeta repertoire was examined from the lesional skin of
      butterfly rash biopsied from 3 cases of systemic lupus erythematosus (SLE).
      Results showed that TCR Vbeta 2 was detected in 6 out of the 7 cases of AESjS,
      although diverse usage was observed. TCR Vbeta 2 and 17 (but particularly Vbeta
      2) were predominantly expressed in AESjS in comparison with paired PBL. In the
      case which presented AESjS at two separate sites, Vbeta 2, 6, 18 and 19 were
      preferentially expressed in both skin sites as compared with PBL. On the other
      hand, TCR Vbeta 6, 13-2 and 14 were commonly demonstrated in the cutaneous
      lesions of SLE. These results suggest that (1) the TCR Vbeta usage by
      infiltrating T cells in AESjS is not strictly limited, however, Vbeta 2 may play
      an important role in the induction of AESjS, and that (2) different subsets of
      TCR Vbeta genes are used in the lesional skin of SjS and SLE, which might account
      for the clinical and histological differences seen in the erythema found in these
      two autoimmune disorders.

PMID- 9649695
TI  - Subcutaneous interleukin-2 and interferon-alpha therapy associated with cisplatin
      monochemotherapy in the treatment of metastatic melanoma.
AB  - The anti-tumoral activity of interleukin-2 (IL-2) is well-documented. Although
      the response rate with this cytokine is low, it appears to be improved when
      associated with interferon-alpha (INF-alpha) and/or cytotoxic drugs. Aim of this
      work was to study the efficacy and tolerance of an ambulatory treatment using
      subcutaneous, low-dose IL-2 with subcutaneous INF-alpha and chemotherapy. We
      report a multicenter study of ambulatory treatment combining subcutaneous (SC)
      low-dose IL-2 (9 x 10(6) IU) with SC INF-alpha-2a (3 x 10(6) IU) and cisplatin
      (100 mg/m2) in 33 patients (13 women and 20 men, 22 to 66 years of age) with
      metastatic malignant melanoma. Metastases were mainly nodal (54.5%) and pulmonary
      (51.5%). For 81.8% of patients, this therapy constituted the firstline treatment.
      The overall response rate at the end of the first maintenance course was 30.3% (3
      complete responses and 7 partial responses). Adverse effects were observed in 28
      patients (84.8%), but were most often minor (grade 1 or 2 on the WHO toxicity
      scale). The results confirmed the good tolerance to SC IL-2 and its suitability
      for ambulatory therapy, as well as the potential benefit of associating IL-2 with
      cisplatin in the treatment of metastatic melanoma (a possibility considered in
      two previous studies).

PMID- 9649696
TI  - Disparate effects of photoprotection on ultraviolet radiation-induced
      immunosuppression.

PMID- 9649697
TI  - Lidocaine-prilocaine cream (EMLA Cream) as a topical anaesthetic for the
      cleansing of leg ulcers. The effect of length of application time.
AB  - Pain prevents the effective cleansing of many leg ulcers. Pain relief during
      debridement has been reported after topical anaesthesia with EMLA cream. The
      purpose of this study was to assess and compare the pain intensity during
      debridement after different lengths of application time of EMLA. Fifty-nine
      patients, stratified for leg ulcer type, were randomised to 10, 20 or 60 minutes
      treatment with EMLA prior to debridement. The pain was rated by each patient on a
      100-mm visual analogue scale (VAS). Pain intensity during debridement decreased
      significantly with increasing duration of EMLA application (p = 0.001). The
      median values of the VAS pain scores were 41, 20 and 8 in the 10-, 20- and 60-
      minute groups respectively. A minimum of 20 minutes application time gives
      substantial pain relief in the majority of patients.

PMID- 9649698
TI  - Immunomodulation by UV light: role of neuropeptides.

PMID- 9649699
TI  - Infundibulocystic basal cell carcinoma.
AB  - We report on a 72-year-old male patient with a solitary, dome-shaped tumor on the
      preauricular region. Histologically, it showed an intradermal basaloid cell tumor
      composed of many anastomosing epithelial cords. There were multiple infundibular
      cystic structures containing corneocytes lined by follicular infundibular
      epithelium and bud-like structures simulating the follicular germs throughout the
      neoplasm. Follicular bulbs and papillae were absent within the tumor. The stroma
      was scant and not highly fibroplastic. The tumor was diagnosed as
      infundibulocystic basal cell carcinoma, a recently described, uncommon variant of
      basal cell carcinoma.

PMID- 9649700
TI  - Guess what! Scrofuloderma (tuberculosis colliquativa cutis) of the left foot.

PMID- 9649701
TI  - The chemokine family. Potential therapeutic targets from allergy to HIV
      infection.
AB  - Basal trafficking and homing of leukocytes is controlled by a large subfamily of
      cytokines, the chemokines. The initiation and perpetuation of an inflammatory
      response is also mediated by the chemokines. The chemokine family acts through a
      sub-family of the seven transmembrane, G-protein-coupled receptor class. Despite
      the large number of chemokine proteins, several factors such as regulated
      expression of the ligands and their receptors, glycosoaminoglycan interactions
      and their signaling mechanisms introduce the required selectivity in vivo.
      Recently, chemokine receptors have been identified as an essential component for
      the infection of host cells by HIV. Chemokine receptors thus present an
      attractive therapeutic target for inflammatory disorders and HIV infection, and
      evidence for their validation using antibodies and receptor antagonists is
      discussed.

PMID- 9649702
TI  - Unilateral demodicidosis.
AB  - A 45-year-old man presented with a unilateral, papulopustular, rosacealike,
      chronic dermatitis which involved the left portion of the forehead and the
      eyelids unilaterally. Many Demodex mites were found in the follicles of the
      affected area. Topical crotamiton cleared the lesions after an unsuccessful trial
      with oral metronidazole. This observation provides further evidence that
      demodicidosis is a condition distinct from common rosacea.

PMID- 9649703
TI  - Cyclosporine A delays wound healing and apoptosis and suppresses activin beta-A
      expression in rats.
AB  - Cyclosporine A is a powerful immunosuppressive agent which is widely used for the
      prevention of allograft rejection and for the treatment of autoimmune diseases.
      Clinical and experimental data show that it may also act on connective tissue. We
      investigated the influence of cyclosporine A on granulation tissue formation and
      wound healing. Using an in vitro approach, we followed the time course of rat
      dermal fibroblasts during wound repair. Granulation fibroblasts were compared to
      dermal fibroblasts flow cytometrically and by mRNA analysis with respect to the
      expression of procollagen alpha1(I), integrin beta1, interleukin-6, transforming
      growth factor beta1, keratinocyte growth factor and activin betaA. The most
      pronounced effect in cyclosporine-treated rats was the strong down-regulation of
      activin beta expression. In cryo-sections of granulation tissue from the same
      rats, the distribution and expression intensity of intercellular adhesion
      molecule and its receptors were investigated by immunohistology. Clearly, a time
      course was detectable. Tissue from CsA-treated animals showed a delay of three
      days compared to untreated animals. Apoptosis was also delayed in CsA-treated
      rats by around three days. Furthermore, we investigated the effect of CsA on the
      expression of collagen alpha1(I), fibronectin and matrix metalloprotease 1 genes
      in dermal fibroblasts from untreated donors. No changes in the mRNA steady state
      levels of these genes were revealed after direct addition of different doses of
      CsA to fibroblast cultures. Our data suggest that CsA may interfere with the
      complicated net of interactions between connective tissue and the immune system
      by down-regulation of the inflammatory phase by modulation of cytokines and a
      subsequent delay of tissue repair.

PMID- 9649704
TI  - Immunomodulation induced by psoralen plus ultraviolet A radiation.

PMID- 9649705
TI  - Sporadic generalized lentiginosis without systemic involvement.
AB  - A 42-year old Caucasian man with generalized, acquired lentiginosis and no other
      associated diseases is described. A brief discussion about the significance of
      the term lentiginoses, the problems of their classification and nomenclature is
      also presented. The presence at the histopathologic examination, of some
      junctional nests of melanocytes provides the basis for a discussion of the
      relationship of the case presented, as well as other lentiginoses, with
      melanocytic naevi.

PMID- 9649706
TI  - Relevance of photo-immunosuppression for viral infections (i.e. human papilloma
      virus).

PMID- 9649707
TI  - Pathogenesis of leukocytoclastic vasculitis.
AB  - There is compelling animal and human experimental evidence that leukocytoclastic
      vasculitis is a hypersensitivity vasculitis, similar in nature to the
      experimental Arthus reaction. The immune complexes formed in antigen excess
      circulate until some event occurs that cause deposition in blood vessel walls.
      Adhesion molecules and cytokines released by endothelial cells and activated
      neutrophils represent a key factor in this process. The membrane attack complex
      of complement plays a significant role in altering the endothelial cell membrane
      integrity. Activated neutrophils release proteolytic enzymes, especially
      collagenases and elastases, along with free oxygen radicals that damage the
      vessel walls and the surrounding tissues. It remains uncertain whether
      antineutrophilic cytoplasmic antibodies, anti-endothelial antibodies and anti
      cardiolipin antibodies are epiphenomena or are directly involved in the disease
      process. Apoptotic cell death mediated by the Fas/Bc12 system is a feature of
      leucocytoclastic vasculitis. In conclusion, the post-capillary venule is the
      active orchestrator of neutrophils in leukocytoclastic vasculitis which mediate a
      complex series of endothelial/leukocyte interactions.

PMID- 9649708
TI  - Photoprotection and photo-immunosuppression in man.

PMID- 9649709
TI  - Variable expression of Mn SOD in three different human melanoma cell lines.
AB  - In recent studies, decreased expression of Mn SOD, an intramitochondrial enzyme
      responsible for the dismutation of anion superoxide, has been reported in
      multiple, malignant cell types, whereas its gene has been proposed as a tumour
      suppressor gene in melanoma. We studied the expression of Mn SOD both at genetic
      (DNA, mRNA) and protein levels in three human melanoma cell lines (M3 Da, M4 Be,
      M1 Do). All cell lines were tumorigenic in a nude mouse model. In these cell
      lines, Mn SOD was studied at the molecular level using PCR of genomic DNA, and by
      RT-PCR of total mRNA extracts to detect Mn SOD transcripts. Mn SOD protein
      expression was studied by indirect immunofluorescence using a monoclonal antibody
      anti-human Mn SOD (Bender) on suspended cells fixed on slides after cytospin. All
      three human melanoma cell lines studied contained detectable amounts of DNA and
      mRNA specific for the Mn SOD gene. In contrast, there was variable expression of
      Mn SOD at the protein level. As detected by immunofluorescence, Mn SOD protein
      was expressed in only two cell lines (strongly in M3 Da, weakly in M4 Be) but not
      in M1 Do. These preliminary, qualitative results demonstrate that the deficit of
      Mn SOD protein expression is variable depending on the particular melanoma cell
      line. Further investigations are required in order to evaluate quantitative Mn
      SOD protein expression and activity as well as the level of functional Mn SOD
      mRNA and DNA in these or other cell lines.

PMID- 9649710
TI  - An immunohistochemical study of UV-induced skin lesions in actinic prurigo.
      Resistance of langerhans cells to UV light.
AB  - Actinic prurigo is an inflammatory disease of the skin that appears to be
      mediated by an abnormal immune response. Cell adhesion molecules play a key role
      in the induction of the immune response as well as in the pathogenesis of
      inflammation. We investigated the expression of cell adhesion and activation
      molecules, as well as the density of Langerhans cells in skin from patients with
      actinic prurigo. Skin biopsies from ultraviolet light-induced lesions, and non
      irradiated areas from 10 actinic prurigo patients were studied; in addition,
      several spontaneous skin lesions were studied. Skin biopsies from normal
      individuals were used as controls. The expression of ICAM-1, ICAM-3, LFA-3, CD2,
      LFA-1, VLA-4, CD1a, VCAM-1, CD69, and activated b1 integrins were assessed by
      immunostaining. An increased expression of LFA-1, LFA-2, ICAM-3, VLA-4, and
      activated b1 integrins was observed in the cell infiltrate of actinic prurigo
      lesions and an up-regulated expression of ICAM-1 was detected in keratinocytes
      from these specimens. Interestingly, the number of Langerhans cells (CD1a + ) in
      actinic prurigo skin was not significantly affected by ultraviolet irradiation, a
      phenomenon that was not observed in normal controls. The increased expression of
      adhesion molecules in the cell infiltrate of actinic prurigo, indicates that
      these cells are activated and suggests that they are involved in the skin damage
      seen in these patients. The resistance of Langerhans cells from patients with
      actinic prurigo to ultraviolet light may have an important role in the
      pathogenesis of this condition. The involvement of keratinocytes in the
      pathogenesis of actinic prurigo is suggested by the expression of ICAM-1 on these
      cells.

PMID- 9649711
TI  - Annular elastolytic sarcoidosis of the face.
AB  - We report a case of facial annular lesions in a non-diabetic, Japanese woman aged
      78, the histopathological study of which showed noncaseating, epithelioid cell
      granuloma with multinucleated giant cells. Together with the aberrant laboratory
      data, these clinical and histopathological findings were considered to be
      compatible with those of sarcoidosis, but elastic tissue stain disclosed the
      existence of elastolytic changes which were clinically and histopathologically
      similar to those found in actinic granuloma or annular elastolytic giant cell
      granuloma. Based on a review of the literature, we believe that several annular
      elastolytic granulomatous diseases of the face form a disease spectrum, some of
      which are identified with intermediate features of these three diseases.

PMID- 9649712
TI  - The pathophysiology of lupus erythematosus.
AB  - Systemic lupus erythematosus disseminatus in addition to the more restricted,
      lupus-like syndromes, is the consequence of an attack by the immune system on the
      cellular and nuclear structures of the body. These disorders are also frequently
      associated with disturbances of the coagulation cascade. In this review paper,
      the factors that provoke or enhance these disturbances are considered, as well as
      the way by which this provocative effect is exerted. An intermutual relation
      between various elements is described, whereby congenital factors (heredity,
      race) and non-congenital factors (sex hormones, pregnancy, environment,
      ultraviolet light, drugs, infection) play a role. These factors induce the
      activation cascade of the disease, via two different axes: on the one hand
      modifications in the DNA structure, on the other immune stimulation. This
      eventually results in tissue damage.

PMID- 9649713
TI  - Pyoderma gangrenosum associated with the secondary antiphospholipid syndrome.
AB  - A 64-year-old woman with an 11-year history of systemic lupus erythematosus and
      amputation of her left lower leg as a consequence of arterial embolism, presented
      with two large, non-healing ulcers on her right shank. Pyoderma gangrenosum
      associated with secondary antiphospholipid syndrome was diagnosed based upon the
      typical clinical features and increased antibodies to cardiolipin. Although an
      aggressive therapy with corticosteroids and cyclosporine was started, her
      condition continued to worsen. She finally died as a result of sepsis. We discuss
      the difficulties in diagnosis and therapy of SLE combined with the
      antiphospholipid syndrome and pyoderma gangrenosum.

PMID- 9649714
TI  - Gowers' local panatrophy.
AB  - We report a patient with Gowers' local panatrophy, who developed skin atrophy on
      the left upper arm, right lower leg and facial hemiatrophy without a thickening
      or a sclerosing process. Histological examination revealed loss of thickness of
      the dermis and subcutaneous tissue. It is suggested that skin atrophy was induced
      by a nonsclerosing process, different from the inflammation and fibrosis observed
      in scleroderma.

PMID- 9649715
TI  - Neurofibromatosis type 1 associated with systemic vasculopathy.
AB  - Systemic vasculopathy in patients with neurofibromatosis type 1 is rare. We
      describe a case of unusual cerebral and renal involvement in a young, 29-year-old
      patient, who died of a cerebral ischemic attack one year after our observation.

PMID- 9649716
TI  - Immunocytochemical demonstration of reduced Cu,Zn-superoxide dismutase levels
      following topical application of dithranol and sodium lauryl sulphate: an
      indication of the role of oxidative stress in acute irritant contact dermatitis.
AB  - Oxidative stress is known to be implicated in the inflammation induced by the
      anti-psoriatic irritant, dithranol. In this study, we wished to investigate
      whether this is reflected in the levels of the antioxidant enzyme, Cu,Zn
      superoxide dismutase, as detected by quantitative immunocytochemistry, and
      whether similar changes also occur following exposure to an irritant not normally
      associated with reactive oxygen species generation, namely sodium lauryl
      sulphate. Analysis of biopsies from patch test sites revealed that significant
      reductions in the epidermal levels of Cu,Zn-superoxide dismutase were induced by
      both dithranol and sodium lauryl sulphate, although the time course of diminished
      activity was different for each irritant. Our findings suggest that oxidative
      stress plays a general role in the pathophysiology of acute irritant contact
      dermatitis.

PMID- 9649717
TI  - A case of chromoblastomycosis due to Phialophora verrucosa responding to
      treatment with fluconazole.
AB  - We report the case of a 40-year-old Filippino woman, with a 5-year history of a
      slowly spreading, painful skin lesion on her left foot. Histological examination
      showed a dermal, granulomatous infiltrate consisting of neutrophils, histiocytes
      and lymphocytes, with "sclerotic bodies" in the cytoplasm of phagocytic cells.
      Mycological culture revealed the presence of Phialophora verrucosa and confirmed
      the histopathological diagnosis of chromo-blastomycosis. Association of surgical
      curettage of the exuberant, infected tissue with systemic fluconazole
      administration gave good therapeutic results with no relevant side effects.

PMID- 9649718
TI  - Segmental arrangement of multiple, partly congenital and partly acquired
      melanocytic nevi.
AB  - A 15 year-old girl presented with numerous congenital melanocytic nevi,
      occasionally hairy, with a segmental distribution at the left pre-auricular
      region. On the left side of the back of the neck there were multiple melanocytic
      nevi with a warty appearance, which had started to appear when she was 5 and
      which had remained stable from the time she was 10. These lesions had a
      distribution reminiscent of an epidermal nevus with a pattern similar to
      Blaschko's lines. On general physical examination there was a moderate degree of
      idiopathic scoliosis, with a left lumbar curvature. Biopsies were taken from both
      types of nevus which were diagnosed as congenital compound melanocytic nevus and
      acquired compound melanocytic nevus respectively. We consider that the segmental
      distribution of the melanocytic nevi of this patient supports the theory that a
      genetic defect determined the appearance of both these congenital and acquired
      lesions.

PMID- 9649719
TI  - Melanin and melanosome complexes in long standing stable vitiligo--an
      ultrastructural study.
AB  - To investigate the presence of melanin and melanocytes (MC) in stable vitiligo,
      skin biopsies from five patients with vitiligo lesions of between 1 to 17 years
      duration were examined under the electron microscope. Areas of the upper dermis
      and epidermis were explored. There was a significant amount of melanin in a few
      keratinocytes (KC) grouped in the stratum basale in 1-3 year-old vitiligo
      lesions. In these KC, the melanosomes were most often aggregated into melanosome
      complexes (MCo) while the remaining KC were completely devoid of melanin.
      Solitary MCo were also observed in a few dermal cells in all vitiligo biopsies.
      All non-keratinocytes were scrutinized in series of 200-300 consecutive sections
      and were identified according to morphological characteristics. Neither active
      nor inactive MC, nor MC dendrites were found. These observations show that
      melanin in non-negligible amounts can be found even in 3 year-old vitiligo
      epidermis. Since there were no MC detected in the epidermis it implies that the
      melanosomes can persist in certain KC for some time after the onset of vitiligo.

PMID- 9649720
TI  - Findings in vivo of Sarcoptes scabiei with incident light microscopy.
AB  - Parasites, especially Sarcoptes scabiei, may represent a difficult diagnostic
      problem. In many cases, the results of the usual methods for the diagnosis of
      scabies, such as microscopic identification, can be negative owing to the small
      number of parasites present in the cornified layer. Moreover, tape stripping or
      removal of mites with a needle is difficult and sometimes painful, and therefore,
      not well accepted. We have evaluated the applicability and usefulness of
      epiluminescence microscopy, a new technique frequently used for the study of
      pigmented lesions of the skin. Thirty seven patients with the presumptive
      clinical and/or anamnestic diagnosis of scabies were enrolled in our study. With
      this method many suspicious sites may be examined within a few minutes without
      causing any harm or discomfort to the patient.

PMID- 9649721
TI  - Prologue: placental-fetal metabolic inter-relationships.

PMID- 9649722
TI  - An overview of early post-partum nutrition and metabolism.

PMID- 9649723
TI  - Nutrient and metabolic needs of the fetus and very small infant: a comparative
      approach.

PMID- 9649724
TI  - Fuel selection: the maternal adaptation to fetal nutrient demand.

PMID- 9649725
TI  - Mechanisms of maternofetal exchange across the human placenta.

PMID- 9649726
TI  - Maternal nutrition and disproportionate placental-to-fetal growth.

PMID- 9649727
TI  - Long-chain polyunsaturated fatty acids: who needs them?

PMID- 9649728
TI  - Milk: integrative signalling between mother and offspring.

PMID- 9649729
TI  - Environmental contaminants in milk: the problem of organochlorine xenobiotics.

PMID- 9649730
TI  - Role of long-chain fatty acids in the postnatal induction of genes coding for
      liver mitochondrial beta-oxidative enzymes.

PMID- 9649731
TI  - Neonatal brown adipose tissue, UCP1 and the novel uncoupling proteins.

PMID- 9649732
TI  - Neonatal metabolic adaptation after preterm delivery or intra-uterine growth
      retardation.

PMID- 9649733
TI  - Impaired neonatal hepatic ketogenesis.

PMID- 9649734
TI  - Total parenteral nutrition in surgical infants.

PMID- 9649735
TI  - Inborn errors of ketogenesis.

PMID- 9649736
TI  - Inborn errors of metabolism in the light of metabolic control analysis.

PMID- 9649737
TI  - Recent developments in the detection of inherited disorders of mitochondrial beta
      oxidation.

PMID- 9649738
TI  - Glycosidase families.

PMID- 9649739
TI  - Mechanisms of cellulases and xylanases.

PMID- 9649740
TI  - The cellobiohydrolases of Trichoderma reesei: a review of indirect and direct
      evidence that their function is not just glycosidic bond hydrolysis.

PMID- 9649741
TI  - Kinetics of fungal cellulases.

PMID- 9649742
TI  - Structural studies on cellulases.
AB  - Recent advances in chemical methodologies, together with the technique of X-ray
      structure analysis, are providing profound structural and mechanistic insights
      into cellulase action. At the structural level, detailed analyses of nearly all
      the enzyme families involved in cellulose breakdown are not known.
      Oligosaccharide complexes for all these enzymes have not yet been described, but
      utilization of the chemistry provided by non-hydrolysable oligosaccharides,
      sugars modified so as to provide long-lived glycosyl-enzyme intermediates, and
      the development of transition-state analogues, should soon extend and develop our
      knowledge of these systems. The way in which enzyme structure dictates reaction
      chemistry is beginning to be more clearly understood.

PMID- 9649743
TI  - Trichoderma reesei cellobiohydrolases: why so efficient on crystalline cellulose?

PMID- 9649744
TI  - The cellulosome of Clostridium thermocellum.

PMID- 9649745
TI  - Structure and function analysis of Pseudomonas plant cell wall hydrolases.

PMID- 9649746
TI  - Superfamilies: the 4/7 superfamily of beta alpha-barrel glycosidases and the
      right-handed parallel beta-helix superfamily.

PMID- 9649747
TI  - Structure, function and protein engineering of starch-degrading enzymes.

PMID- 9649748
TI  - Specificity of ferulic acid (feruloyl) esterases.

PMID- 9649749
TI  - Molecular and intracellular events in the assembly and secretion of chylomicrons
      by enterocytes.

PMID- 9649750
TI  - The role of gastrointestinal hormones in carbohydrate and lipid metabolism and
      homeostasis: effects of gastric inhibitory polypeptide and glucagon-like peptide
      1.

PMID- 9649751
TI  - Modification of the gut flora by dietary means.

PMID- 9649752
TI  - Effect of non-digestible fermentable carbohydrates on hepatic fatty acid
      metabolism.

PMID- 9649753
TI  - Salvage of urea-nitrogen in the large bowel: functional significance in metabolic
      control and adaptation.

PMID- 9649754
TI  - Bcl-2 as a possible sensor of nutritional stress inhibiting apoptosis and
      allowing cell survival during colorectal carcinogenesis.

PMID- 9649755
TI  - Plasmalogen-selective phospholipase A2 and its involvement in Alzheimer's
      disease.

PMID- 9649756
TI  - The role of docosahexaenoic acid in brain development and fetal alcohol syndrome.

PMID- 9649757
TI  - Do long-chain polyunsaturated fatty acids influence infant cognitive behaviour?

PMID- 9649758
TI  - Role of apolipoprotein E in modulating neurite outgrowth: potential effect of
      intracellular apolipoprotein E.

PMID- 9649759
TI  - Apolipoprotein E and neuronal plasticity following experimental de-afferentation
      and in Alzheimer's disease.

PMID- 9649760
TI  - Pharmacological, physiological and clinical implications of the discovery of
      cannabinoid receptors.

PMID- 9649761
TI  - Herpes simplex virus type I in brain and the type 4 allele of the apolipoprotein
      E gene are a combined risk factor for Alzheimer's disease.

PMID- 9649762
TI  - A simple method for the extraction and quantification of daidzein and genistein
      in food using gas chromatography mass spectrometry.

PMID- 9649763
TI  - Flux control exerted by mitochondrial outer membrane carnitine
      palmitoyltransferase over ketogenic flux in hepatocytes isolated from suckling
      rats.

PMID- 9649764
TI  - Gestational and neonatal expression and activity of human hepatic 3-hydroxy-3
      methylglutaryl-CoA synthase.

PMID- 9649765
TI  - Effect of maternal fatty acid supply on umbilical cord and piglet tissue
      composition.

PMID- 9649766
TI  - Beta-oxidation in neonatal cardiac mitochondria.

PMID- 9649767
TI  - Ca2+ inhibits Mg(2+)-mediated trophoblast cell adhesion to extracellular matrix
      in vitro.

PMID- 9649768
TI  - Transition metal cations potently mediate adhesion of trophoblast cells to
      extracellular matrix in vitro.

PMID- 9649769
TI  - Choline metabolism in the neonatal period.

PMID- 9649770
TI  - The general transcription factor Sp1 plays an important role in the regulation of
      fatty acid synthase.

PMID- 9649771
TI  - Expression of a sodium-dependent L-carnitine transporter in lactating rat mammary
      tissue.

PMID- 9649772
TI  - Prematurity: influence of atopic status and infant feeding practices on specific
      IgG levels in cord and infant serum.

PMID- 9649773
TI  - Hyperleptinaemia precedes hyperinsulinaemia in Zucker (fa/fa) rats.

PMID- 9649774
TI  - Copper and iron interactions in a placental cell line (BeWo).

PMID- 9649775
TI  - Growth sensitive genes expressed in the placenta.

PMID- 9649776
TI  - The role of polyamines in pregnancy.

PMID- 9649777
TI  - Changes in ferrozine detectable iron in liver cells during hypoxia and
      hypothermia.

PMID- 9649778
TI  - Screening for the trifunctional protein G1528C mutation in alcoholic liver
      disease.

PMID- 9649779
TI  - Problem-based learning in modular science degrees.

PMID- 9649780
TI  - Are we getting W.I.S.E. (Women Into Science and Engineering) or do we still have
      W.A.S.T.E. (Women Averse Science, Technology and Engineering).

PMID- 9649781
TI  - Distribution and activities of neuronal protein 4.1 isotypes.

PMID- 9649782
TI  - Intracellular localisation of beta I sigma 2 spectrin with GLUT4 vesicles.

PMID- 9649783
TI  - A method for the measurement of [3H]-glutamate release from cultured dorsal root
      ganglion neurons.

PMID- 9649784
TI  - Interaction of synapsin IIb with calmodulin: identification of a high affinity
      site.

PMID- 9649785
TI  - Interaction of synapsin I with actin and SSVs: differential regulation by
      calmodulin.

PMID- 9649786
TI  - The effect of cytochalasin D and colcemid on noradrenaline release in the human
      neuroblastoma SH-SY5Y.

PMID- 9649787
TI  - CPT (8-cyclopentyl theophylline) corrects CFTR antibody inhibited mucin
      secretion.

PMID- 9649788
TI  - Remodelling glycans on IgG by genetic re-engineering.

PMID- 9649789
TI  - Physiological influences on recombinant IgG glycosylation.

PMID- 9649790
TI  - Genetic engineering of alpha 2,6-sialyltransferase in recombinant CHO cells.

PMID- 9649791
TI  - Fragmentation patterns of human paranasal sinus mucins.

PMID- 9649792
TI  - MUC5B expression in middle ear mucosal glands.

PMID- 9649793
TI  - Protein glycosylation and peripheral vascular disease in diabetic patients.

PMID- 9649794
TI  - Protein-protein and protein-lipid interactions of the CaLB domain.

PMID- 9649795
TI  - Identification of a monocarboxylate transporter isoform type 1 (MCT1) on the
      luminal membrane of human and pig colon.

PMID- 9649796
TI  - Sequence comparisons of ruminant renal Na+/phosphate co-transporters.

PMID- 9649797
TI  - Isolation of a RT-PCR fragment from human colon and sheep rumen RNA with
      nucleotide sequence similarity to human and rat urea transporter isoforms.

PMID- 9649798
TI  - Molecular modelling of the mechanism of bile acid transport by the hepatocyte
      canalicular ecto-ATPase (CAM-105).

PMID- 9649799
TI  - Does glutathione flush reduce acute cellular rejection in liver allografts?

PMID- 9649800
TI  - Adhesion molecule activation and hepatocyte damage following orthotopic liver
      transplantation (OLT).

PMID- 9649801
TI  - A GFP-PKC fusion protein to investigate the mechanism of PKC down-regulation.

PMID- 9649802
TI  - Serum total antioxidant status during vascular surgery.

PMID- 9649803
TI  - Regulation of phospholipase C delta 1 activity by GTP-binding proteins: rhoA as
      an inhibitory modulator.

PMID- 9649804
TI  - Synthesis and characterization of tagged human oxytocin receptors (hOTRs).

PMID- 9649805
TI  - ADP-ribosyltransferase inhibitors and pseudo-substrates inhibit rat smooth muscle
      cell migration in vitro.

PMID- 9649806
TI  - PPADS and extracellular ATP both mediate endothelial dependent relaxation of
      guinea pig aorta.

PMID- 9649807
TI  - Regulation of phospholipase C gamma 1 activity by GTP-binding proteins in
      vascular smooth muscle.

PMID- 9649808
TI  - Differential expression of phospholipase C delta 1 in Wistar Kyoto compared to
      spontaneously hypertensive rats.

PMID- 9649809
TI  - Streptozotocin-induced diabetes is associated with increased renal lipoxygenase
      activity.

PMID- 9649810
TI  - The significance of 2' and 3' aminoacylation of RNA in the origin of amino acid
      homochirality.

PMID- 9649811
TI  - Angiotensin-converting enzyme (ACE) gene polymorphism and alcoholism.

PMID- 9649812
TI  - Angiotensin-converting enzyme (ACE) gene polymorphism in patients with
      sarcoidosis.

PMID- 9649813
TI  - Selective expression of a novel striated muscle protein.

PMID- 9649814
TI  - Autocatalytic processing of mutant SIV-PR polyproteins.

PMID- 9649815
TI  - Free radical analysis via ESR spectroscopy during vascular surgery.

PMID- 9649816
TI  - Kinetics of reactive oxygen intermediate formation and apoptosis in human glioma
      and glioma C6 cell line: effects of radiation and n-6 essential fatty acids.

PMID- 9649817
TI  - Depletion of docosahexaenoic acid in red blood cell membranes of depressive
      patients.

PMID- 9649818
TI  - Interactions of nitric oxide, free radicals and polyamines in the membrane
      pathology of schizophrenia.

PMID- 9649819
TI  - The production of a transgenic rat expressing nerve growth factor using cell-type
      specific keratin promoters.

PMID- 9649820
TI  - Effect of insulin and serum on lipoprotein lipase in lactation.

PMID- 9649821
TI  - C-terminal His6-tagged lecithin-cholesterol acyltransferase (LCAT) is
      catalytically active.

PMID- 9649822
TI  - Immunoaffinity-isolation of plasma lecithin-cholesterol acyltransferase (LCAT)
      from patients with hepatic cirrhosis.

PMID- 9649823
TI  - Plasma, platelet and erythrocyte lipids in the Watanabe heritable hyperlipidaemic
      (WHHL) rabbit.

PMID- 9649824
TI  - Chylomicron remnants derived from fish oil are bound and internalised more
      rapidly by isolated hepatocytes than those derived from olive or palm oil.

PMID- 9649825
TI  - Effects of oestrogen on plasma, hepatic and biliary cholesterol levels in rats
      fed fish oil.

PMID- 9649826
TI  - Biochemical studies of oil biosynthesis in olive (Olea europea) and oil palm
      (Elaeis guineensis) callus cultures.

PMID- 9649827
TI  - Characteristics of wheat seed lipase.

PMID- 9649828
TI  - Genetic mechanisms involved in the adaptation of marine algae to heavy metal
      pollution.

PMID- 9649829
TI  - Reaction products of the lipoxygenase pathway in olive tissue cultures.

PMID- 9649830
TI  - The effects of Iprodione on the lipid metabolism of Botrytis cinerea.

PMID- 9649831
TI  - Trans monounsaturated fatty acid and the oxidation of low density lipoproteins.

PMID- 9649832
TI  - Trans mono-unsaturated fatty acids and tissue factor activity in a monocytic cell
      line.

PMID- 9649833
TI  - Modulation of colonocyte proliferation and apoptosis by dietary fish oil in
      experimental colorectal carcinogenesis.

PMID- 9649834
TI  - The effect of prostaglandin E2 on the intracellular lipolysis of triacylglycerol
      in cultured rat hepatocytes.

PMID- 9649835
TI  - Crystallising the LH1-RC "core" complex of purple bacteria.

PMID- 9649836
TI  - Effects of indomethacin on mitochondrial ATP synthesis.

PMID- 9649837
TI  - Effects of indomethacin on mitochondrial oxygen uptake in intestine.

PMID- 9649838
TI  - Adenosine deaminase activity: to be an useful marker in distinguishing pleural
      effusions due to malignancy from tuberculosis.

PMID- 9649839
TI  - Identification of active site residues in a ferulic acid esterase (FAE-III) from
      Aspergillus niger.

PMID- 9649840
TI  - Stability of feruloyl esterases from Aspergillus.

PMID- 9649841
TI  - Properties of ferulate dimers from plant cell walls.

PMID- 9649842
TI  - Three distinct ferulic acid esterases produced by Aspergillus niger have
      specificities for different phenolic-sugar linkages in plant cell walls.

PMID- 9649843
TI  - Enzymic hydrolysis of diferulates from wheat bran cell walls.

PMID- 9649844
TI  - Plant cell wall degrading enzyme complexes from the cellulolytic rumen bacterium
      Ruminococcus flavefaciens.

PMID- 9649845
TI  - Determination of the catalytic site content of a polyclonal catalytic antibody
      preparation.

PMID- 9649846
TI  - Sensitivities of transition state geometries to P1-P2 binding in reactions of
      papain and actinidin.

PMID- 9649847
TI  - The kinetically influential ionizations of caricain D158N revealed by using 4,4'
      dipyrimidyl disulfide as a reactivity probe.

PMID- 9649848
TI  - Detection of a free enzyme isomerisation in actinidin catalysed hydrolysis.

PMID- 9649849
TI  - The role of Mg2+ in biotin carboxylation in pyruvate carboxylase.

PMID- 9649850
TI  - Production of a yeast cell wall degrading enzyme, beta-1,3-glucanase by
      recombinant Bacillus subtilis.

PMID- 9649851
TI  - Use of argentation TLC with GC to resolve C18:1 fatty acid isomers in test and
      commercial spreads.

PMID- 9649852
TI  - Effects of body size on postprandial lipid metabolism in postmenopausal women.

PMID- 9649853
TI  - Effect of the bile acid: fatty acid ratio on in vivo essential fatty acid
      absorption in the rat.

PMID- 9649854
TI  - Functional expression of Na(+)-independent bile acid transport in Xenopus laevis
      oocytes following injection with pig intestinal mRNA.

PMID- 9649855
TI  - Sugar analogues as potential inhibitors of the intestinal Na+/glucose co
      transporter (SGLT1).

PMID- 9649856
TI  - Cloning and characterisation of the ovine intestinal Na+/D-glucose cotransporter
      (SGLT1) promoter.

PMID- 9649857
TI  - Trimethylamine N-oxide as a probable source of urinary dimethylamine in man; a
      statistical approach.

PMID- 9649858
TI  - Mechanisms of inhibition of hepatic secretion of very low density lipoproteins by
      dietary fish oils.

PMID- 9649859
TI  - Lactose [13C]Ureide as a marker for colonic fermentation and the deconvolution of
      a complex 13CO2 breath test curve.

PMID- 9649860
TI  - Pea flour digestibility and fermentability measured with 13C isotopes.

PMID- 9649861
TI  - The effect of a three week high fat diet on the mouth to caecum transit time of a
      high fat meal in humans.

PMID- 9649862
TI  - Faecal concentrations of biologically active diacylglycerols in humans.

PMID- 9649863
TI  - Influence of lipid content of testmeal on gastrointestinal handling and metabolic
      partitioning of dietary lipid in young men.

PMID- 9649864
TI  - Gastrointestinal transit adaptation to low- and high-fat cafeteria diets.

PMID- 9649865
TI  - Gastrointestinal transit adaptation to high-fat diet in the rat.

PMID- 9649866
TI  - Copper and iron homeostasis in mammalian cells and cell lines.

PMID- 9649867
TI  - Feeding and vigilance behaviour of breeding ostriches (Struthio camelus) in a
      farming environment in Britain.
AB  - 1. Vigilance and feeding behaviour of male and female adult breeding ostriches
      were recorded to determine feeding and scanning bout lengths, a time budget and
      the pattern of vigilance immediately after food was provided. 2. Males were more
      vigilant and fed for shorter periods than females immediately after concentrate
      food was delivered but not throughout the whole day. 3. Most interscan periods of
      males were below 40 s with a maximum of 90 s compared with most interscan periods
      of females lasting less than 70 s with a maximum of 160 s. 4. Gender differences
      in behaviour are attributed to increased male vigilance for predators and/or
      conspecifics, and increased female feeding required for egg production and
      greater opportunity to feed because of male vigilance.

PMID- 9649868
TI  - Feather pecking in growers: a study with individually marked birds.
AB  - 1. The aim of the present study was to investigate whether individual birds
      specialise in feather pecking. Growers were individually marked and reared in
      groups of 30 or 31 in pens with a slatted floor. At an age of 4 to 6 weeks
      feather pecking was frequent in all pens. 2. On average 83% of all group members
      (10 groups, experiment 1) were recorded at least once as initiator of a feather
      pecking interaction. In each group 2 to 6 individuals feather pecked more than
      twice as often as the average for the group, and were defined as 'high rate
      peckers'. They initiated 39% of all recorded feather pecking interactions. 3.
      Every interaction was classified (with increasing intensity) as pecking,
      pinching, pulling or plucking. Compared to the others, 'high rate peckers' had
      more of their feather pecking classified as plucking and less classified as
      pecking. 4. There was no evidence that particular individuals specialised in
      pecking at other specific birds, at specific areas of the body or at birds
      engaged in specific activities. 5. Growers (3 groups, experiment 2) that had just
      feather pecked engaged in more feather pecking during a subsequent 2-min focal
      observation than control birds that had not pecked before the start of the
      observation. 6. It was concluded that feather pecking interactions are clustered
      in time and that the behaviour is not performed by just a few members of a group.
      However, some individuals are characterised by relatively high rates and more
      severe forms of feather pecking.

PMID- 9649869
TI  - Factors affecting the use of perches in cages by laying hens.
AB  - 1. Three experiments were carried out with ISA Brown laying hens housed in
      individual cages with softwood perches of rectangular cross section fitted across
      the width of each cage, to investigate factors affecting the tendency of hens to
      lay their eggs from the perches and to use perches at other times. These factors
      were perch width and angle and method of perch introduction. 2. In experiment 1
      there were 4 treatments. Perches were 38 or 60 mm wide; half of each width were
      flat and half were fixed at 8 degrees, parallel to the slope of the floor. In 2
      similar trials (with 48 and 44 birds respectively, equally divided between
      treatments) birds were moved to experimental cages already fitted with perches.
      Birds with 38 mm, sloping perches laid less than one third of their eggs from the
      perch (31% and 9% in the two trials) while those with the other designs laid more
      than 80% from the perch. Narrow sloping perches were not otherwise aversive and
      there was no consistent variation between treatments in total time perching. 3.
      In experiment 2, 32 birds were allowed to start laying on the floor of the
      experimental cages then perches were introduced at 24 weeks with 8 birds on each
      of 4 treatments: 50 mm perches fixed flat and 38 mm perches fixed flat, and at 5
      and 10 degrees respectively. Only 27% of eggs were laid from the perches with no
      variation between treatments either in this behaviour or in total time perching.
      4. Experiment 3 provided 24 of the birds from experiment 2 with double-length
      perches to determine whether they showed preferences for the design features
      under consideration. Either half the perch length was flat and half sloping at 10
      degrees or half was 38 and half 50 mm wide. Again a relatively low proportion of
      eggs was laid from the perches (18%) and birds showed no significant preference
      for different perch designs as indicated by either how much they perched or where
      they perched. 5. These results suggest that both perch design and the way pullets
      are introduced to perches influence the proportion of perch-laid eggs. They
      confirm that in some circumstances laying from perches can be a serious problem,
      but that in other circumstances incidence can be reduced to a manageable
      frequency. Perches may therefore be practical in commercial production without
      increasing the number of cracked eggs. The results are also likely to be
      applicable in cages with other facilities including nest boxes.

PMID- 9649870
TI  - Wet litter and perches as risk factors for the development of foot pad dermatitis
      in floor-housed hens.
AB  - 1. An experiment was conducted to determine whether different moisture levels of
      litter and perches with different hygienic conditions are involved in the
      manifestation of foot pad dermatitis in White Leghorn layers. 2. Four different
      treatments were compared: dry litter and dry perches; dry litter and wet perches;
      wet litter and dry perches; and wet litter and wet perches. Temperature, pH, air
      humidity and ammonia changes in the pens were monitored. 3. The mean prevalence
      of foot pad lesions in groups 1, 2, 3 and 4 was 17%, 13%, 49% and 48%
      respectively. The overall incidence of foot pad lesions in birds reared on dry
      litter was 38%, and in birds reared on wet litter 92%. 4. When the air
      temperature was above 20 degrees C, an increasing moisture content in the litter
      was associated with an increasing incidence of foot pad dermatitis. However, when
      the air temperature was below 20 degrees C there were no new cases of dermatitis
      in any of the 4 treatments. There were no significant differences in litter pH or
      ammonia between the 4 treatments when compared over the whole experiment. 5.
      Although the incidence of lesions was not significantly affected by the presence
      of wet perches, the area of the lesions tended to be in groups with wet patches
      than in groups with dry perches. 6. It is suggested that moisture and temperature
      are important contributing factors for the occurrence of foot pad dermatitis in
      laying hens. Wet perches may contribute to the severity of such lesions.

PMID- 9649871
TI  - Effect of cage area, cage height and perches on feather condition, bone breakage
      and mortality of laying hens.
AB  - 1. The health of 2 flocks of 896 ISA Brown laying hens were studied successively
      over the years 1995 and 1996 under different caging conditions. Hens were kept in
      groups of 4 in a total of 224 cages. The treatments (7 different types of cages)
      differed in area per hen (450, 600 or 800 cm2) and height (40 or 60 cm). In the
      large (800 cm2/hen) and high (60 cm cage) treatment, half of the cages were
      equipped with perches (20 cm/hen). Each study lasted 48 weeks. 2. Feather
      condition was found to be independent of cage type. 3. No differences were
      apparent between the 7 treatments in tibia breaking strength (using the 3-point
      breakage technique). A significant increase in humerus breaking strength was
      observed in the high cages. The frequency of broken wings recorded after
      slaughter was lower in high cages (23%) than in low ones (36%). 4. Mortality was
      different between treatments. This was explained by a higher proportion of birds
      killed by 'body cannibalism' in the 60 cm high cages, and by a higher proportion
      of birds killed by 'vent cannibalism' in the cages with perches.

PMID- 9649872
TI  - UK survey of broiler ascites and sudden death syndromes in 1993.
AB  - 1. The mean incidence of deaths from ascites in the UK in 1993 was 1.4% (0.7% in
      1991 and 0.9% in 1992) and 0.8% from sudden death syndrome (SDS). In total, the
      economic loss to the UK Broiler Industry in 1993 as a result of these 2
      conditions was 24 Pounds M. 2. Clear geographical differences emerged in the
      occurrence of ascites, with, not only the lowest incidences being observed in
      Northern Ireland, but also the peak of the mortality from ascites occurring much
      later in the rearing cycle than in other regions on the mainland. 3. In all
      regions the incidence of SDS was lower than that of ascites but the reason for
      this disparity remains to be established. 4. Some of the variables associated
      with the road transportation of day-old chicks from the hatchery to the farm
      appeared to influence the incidence of ascites. These included distance or time
      travelled, stocking density, internal lorry temperature and the length of time
      the lorry was heated before transport as well as the time the shed was heated
      before chick arrival. Temperature was also an important factor during growth
      (brooding and finishing). 5. Negative pressure-powered ventilation was preferred
      in most organisations but more ascites was seen with positive pressure
      ventilation. However, the lowest incidence of ascites occurred with natural
      ventilation. There was more ascites relative to shed orientation when the wind
      direction was from the west compared to the east. 6. This survey identifies the
      extent of the problem of broiler ascites in the UK and also highlights the
      importance of good management control of day-old chicks, not only following
      placement, but even before their arrival on the farm.

PMID- 9649873
TI  - Comparison of sex-linked dwarf genes in chickens from two sources when
      introgressed into unrelated genetic backgrounds.
AB  - 1. Sex-linked dwarfing genes from 2 broiler stock origins (EU and US) were each
      introgressed into 2 White Leghorn populations that had been divergently selected
      for antibody response to sheep erythrocytes. 2. When the resulting backcrossed
      populations were 87.5% of their respective. White Leghorn line, non-dwarf pullets
      were assessed for body weights, shank lengths, immunoresponsiveness, age and body
      weight at sexual maturity, egg production, average egg weight, and duration of
      fertility. For measurements where there were no differences between non-dwarf
      pullets from the 2 origins of the dwarfing genes, then the dwarf pullets (which
      were full sisters to the non-dwarfs) were compared. 3. Shank length at 8 weeks of
      age and mature (24-week) body weights were higher for dwarf pullets from EU than
      US dwarf origin. Immune response and several egg production traits were higher
      for dwarf pullets from the high antibody backcross than from those of the low
      antibody backcross. 4. There were few differences in expression of the dwarfing
      genes from 2 origins in the unrelated backcross populations used in this study.
      Also each of the dwarfing genes, when introgressed into different genomic
      backgrounds, was not discernibly different in its expression in terms of antibody
      response or egg production characteristics.

PMID- 9649874
TI  - Nuclear magnetic resonance imaging as a tool to estimate the mass of the
      Pectoralis muscle of chickens in vivo.
AB  - 1. Nuclear magnetic resonance imaging (MRI) was used to assess the advantages of
      the technique in determining the size (volume) and shape of the Pectoralis muscle
      (Pectoralis major and minor) in broiler chickens, non-invasively and in vivo. 2.
      The imaging was performed using a Spectroscopy Imaging System 2.0 Tesla/31 cm
      bore imaging spectrometer. Three-dimensional reconstruction of transverse images
      was used to estimate the size of the Pectoralis muscle of chickens ranging in
      body weight from 362 to 1643 g. 3. Regression analysis resulted in R2 values of
      0.92 and 0.99 for the relationship between Pectoralis muscle weight, body weight
      and muscle volume, respectively. 4. It is concluded that MRI and 3-dimensional
      image reconstruction may be used to estimate the Pectoralis muscle size and
      shape. This may be readily extended to monitor the influence of various factors
      on the growth and development of specific organs and tissues in the body.

PMID- 9649875
TI  - Organic matrix morphology and distribution in the palisade layer of eggshells
      sampled at selected periods during lay.
AB  - 1. 1 cm2 pieces of eggshells from a commercial battery flock were plasma etched
      to remove the outer shell membranes. 2. They were decalcified using EDTA (200
      g/l, pH 6.9 to 7.0) in paraformaldehyde (20 g/l) and 25% gluteraldehyde (20 ml in
      0.98 l) in phosphate buffer, then prepared for light and transmission electron
      microscopy. 3. Light microscopy revealed a differential distribution of matrix
      material within all 3 regions of the palisade layer at the beginning of lay. 4.
      Transmission electron microscopy revealed a more even distribution of matrix at
      the beginning of lay, although morphological differences were observed. At the
      end of lay all 3 regions showed an increase in % matrix and vesicles/10 cm2 of
      micrograph compared to the middle and beginning of lay periods. 5. It is
      hypothesised that matrix vesicles are involved in the regulation of the
      physiochemical environment within the forming eggshell and that the decline in
      shell quality associated with the end of lay is related to a concomitant change
      in matrix quality.

PMID- 9649876
TI  - Antimicrobial efficacy of AvGard carcase wash under industrial processing
      conditions.
AB  - 1. The efficacy of the AvGard Trisodium Phosphate (TSP) immersion carcase wash
      process was evaluated during 5 industrial trials against Salmonella,
      Enterobacteriaceae, thermotolerant coliforms and total aerobic count. The effect
      against Pseudomonas was also studied in the first 3 trials. 2. Dramatic
      reductions in Salmonella incidence were seen using a whole carcase rinse method.
      In 4 of the 5 trial sites, only one positive sample was found after AvGard
      treatment (average 0.5% incidence), in spite of an average control incidence of
      57.7%. In the 5th site, a water-chilled broiler plant, an average control
      incidence of 74.0% was reduced to 9.4% after AvGard treatment. 3. In the latter
      case, Most Probable Number (MPN) analyses were performed on some of the
      Salmonella positive samples taken from the control and post-treatment series; the
      average MPN count per carcase on controls was 115, whereas for AvGard treated
      birds the figure was only 0.6 per carcase, a greater than 2 log reduction. 4. In
      addition, AvGard treatment gave average log reductions for all trials of:
      Enterobacteriaceae; 2.5 log; Coliforms; 2.7 log, and Total Aerobic Count; 1.1
      log, leading to carcases substantially free of Gram negative pathogens. 5.
      Pseudomonas was reduced by an average of 1.7 log in the first 3 trials,
      dramatically reducing the carcase loading of this important spoilage organism.

PMID- 9649877
TI  - Effect of dietary administration of oil extracts from rosemary and sage on lipid
      oxidation in broiler meat.
AB  - 1. Oxidation of meat and membrane from broilers fed on a diet containing 500
      mg/kg rosemary and sage extracts was compared to meat and membrane oxidation from
      broilers receiving a control diet (not enriched with antioxidants) and a diet
      enriched in alpha-tocopheryl acetate (200 mg/kg). 2. After 9 d of refrigerated
      storage, thiobarbituric acid reactive substances of white meat from broilers fed
      on the control and the alpha-tocopheryl acetate-enriched diets were 0.51 and 0.25
      mg malonaldehyde/kg meat, respectively. Values for meat from broilers fed on the
      diets containing the rosemary and sage extracts were in the range 0.30 to 0.35 mg
      malonaldehyde/kg meat, significantly lower than those from birds fed on the
      control diet. A similar trend was observed in the dark meat but differences were
      not significant at 9 d of storage. Similar trends were observed in raw samples
      stored at -20 degrees C for up to 4 months and in samples cooked at 70 degrees C
      and kept stored under refrigeration for up to 4 d. 3. The meat from broilers fed
      on the diet containing spice extracts had smaller concentrations of total
      cholesterol oxidation products (COPS) than meat from the control group (P <
      0.05). Supplemental alpha-tocopheryl acetate reduced the COPS concentrations to a
      greater extent than did spice extracts (P < 0.05). 4. A similar trend was
      observed in microsomal fraction isolates, in which the rate of
      metmyoglobin/hydrogen peroxide-catalysed lipid peroxidation was lower in animals
      receiving spice extracts than in those fed on the basal diet.

PMID- 9649878
TI  - Decreasing profile of residual sulphaquinoxaline in eggs.
AB  - 1. Sulphaquinoxaline (SQ) was added to the diet of laying hens at 200 mg/kg for 7
      successive days. Contents (mg/kg) of SQ in albumen and egg yolk of eggs laid
      after drug withdrawal were determined by high pressure liquid chromatography
      (HPLC). The contents in the whole egg were calculated taking into consideration
      the respective weights of albumen and egg yolk. 2. A time-lag in the initiation
      of decrease of SQ from eggs after the withdrawal of dietary SQ was observed. 3.
      The decreasing pattern from whole egg could be well described by the following
      equation with a time-lag of 1.0 d, y = 2.07 e-0.5620(t-1.0), where y is the SQ
      content in whole egg, t is time (d) after the withdrawal of dietary SQ and a
      constant of 2.07 is the SQ content in whole egg laid at the withdrawal. 4.
      Biological half-life of SQ in the whole egg was estimated to be 1.23 d. 5. From
      the above equation, SQ residue of whole egg laid at 9th d after withdrawal will
      be below the detection limit of 0.01 mg/kg.

PMID- 9649879
TI  - Comparison of the utilisation of palm kernel meal, brewers' dried grains and
      maize offal by broiler chicks.
AB  - 1. Palm kernel meal (PKM), brewers dried grains (BDG) and maize offal (MO) were
      included in broiler diets, each at 100, 150 or 200 g/kg; the diets were fed up to
      35 d of age. 2. Overall food intake and weight gain decreased in the order BDG,
      PKM and MO. There were, however, significant interactions between the test
      ingredients and dietary concentrations in all the growth responses. Food intakes
      increased with the dietary concentrations of each test ingredient, but the
      increase was greater for BDG than PKM or MO. For weight gain, at 100 g/kg, the
      final body weights of the chicks fed on the diets with BDG and MO were similar,
      and those of chicks fed on the diet with PKM slightly lower. However, at 200
      g/kg, growth rate of chicks fed on the BDG and PKM diets were similar while those
      of chicks fed on the MO diet was 7% lower. Efficiency of food utilisation was
      similar at 100 g/kg for all the ingredients and decreased as their concentrations
      increased; however, the decrease was considerably less for the PKM than for the
      MO and BDG diets. 3. Broilers fed on the BDG-based diets voided most excreta
      followed by those fed on the PKM and MO diets; excreta water content was highest
      from birds fed on the MO diets followed by the PKM and BDG diets. Apparent
      retention of dry matter was similar with all the test ingredients, but it
      decreased only significantly at 200 g/kg dietary concentration. The rate of
      passage was faster with the PKM diets followed by the MO and BDG diets; it was
      increased at 200 g/kg dietary concentration of the test ingredients.

PMID- 9649880
TI  - Influence of dietary protein and sex on walking ability and bone parameters of
      broilers.
AB  - 1. The study was conducted to investigate the effect of dietary protein on the
      walking ability and bone parameters of broilers reared under summer temperatures
      which ranged from 26 degrees to 32 degrees C (+/- 2 degrees C). 2. Three
      different dietary protein combinations were used. The diets (per kg) were: low
      protein with 205 g crude protein and 12.94 MJ ME, 184 g crude protein and 12.75
      MJ ME; medium protein with 219 g crude protein and 12.99 MJ ME, 201 g crude
      protein and 12.87 MJ ME; and high protein with 238 g crude protein and 12.99 MJ
      ME, 216 g crude protein and 12.96 MJ ME from 0 to 4 and 4 to 7 weeks of age,
      respectively. Body weights of birds were recorded and birds' walking ability
      (gait scoring) were scored for each bird, according to 3 categories (completely
      normal to immobile, at 4 and 7 weeks). Tibia parameters and tibia plateau angles
      were also determined at 7 weeks. 3. Birds fed on the low protein were lighter
      than those fed on the medium or high protein diets. At 7 weeks, birds with poor
      walking ability weighted 149 g less than birds with no walking difficulty. 4.
      Bone parameters were not affected by dietary protein, sex or gait score. There
      was a significantly positive correlation between bone strength and radiographic
      density. Bone strength was also significantly correlated with bone weight and
      length.

PMID- 9649881
TI  - Effect of supplementing the hen's diet with vitamin A on the accumulation of
      vitamins A and E, ascorbic acid and carotenoids in the egg yolk and in the
      embryonic liver.
AB  - 1. The effect of a range of supplementations of vitamin A to the laying hen on
      the concentration of vitamins A, E, ascorbic acid and carotenoids in the maternal
      liver, the egg yolk and the embryonic liver were investigated. 2. Four groups of
      25 Rhode Island Red hens were fed on standard layer-breeder diets with
      concentrations of supplemented vitamin A ranging from 0 to 120 micrograms/g
      retinol equivalents from 28 weeks of age. After 3 months, the concentration of
      vitamin A in the maternal liver was found to be greatly enhanced in proportion to
      the increasing rates of supplementation with the vitamin. However, the
      concentration of vitamin E in the maternal liver was markedly reduced by high
      dietary contents of vitamin A. 3. The concentration of vitamin A in the yolk of
      the hens' eggs was markedly increased by the dietary supplementation. However,
      the concentration of both vitamin E and carotenoids in the yolks were
      significantly reduced by high dietary contents of vitamin A. 4. The concentration
      of vitamin A in the liver of the embryo and the day old chick was greatly
      increased by the high concentrations of maternal vitamin A provision. However,
      the concentration of vitamin E, carotenoids and ascorbic acid in the
      embryonic/neonatal liver were significantly reduced by high contents of vitamin A
      in the maternal diet. 5. The susceptibility of the embryonic/neonatal liver to
      lipid peroxidation was significantly increased as a result of high provisions of
      maternal vitamin A. 6. It is concluded that excessive provision of vitamin A to
      the laying hen results in an adverse effect on vitamin E, carotenoids and
      ascorbic acid in the embryonic/neonatal liver and can compromise the antioxidant
      status of the progeny.

PMID- 9649882
TI  - Energy and protein metabolism between 3 and 6 weeks of age of male broiler
      chickens selected for growth rate or for improved food efficiency.
AB  - 1. A new open-circuit respiration unit consisting of 6 respiration chambers, gas
      analysis unit and data-acquisition system is briefly described. 2. Energy and
      protein metabolism in broiler lines selected for improved food efficiency (FC) or
      for growth rate (GL) were measured weekly from 3 to 6 weeks of age. 3. Gross and
      apparent metabolisable energy intake per kg W0.75 was on average higher for GL
      than for FC chickens without differences in metabolisability. Fed and fasted heat
      production per kg W0.75 did not differ between the lines. FC chickens retained
      less energy per kg W0.75 than GL chickens. 4. FC chickens deposited much less of
      the retained energy as fat than their GL counterparts and also showed greater
      protein conversion efficiency. The leaner composition of the body weight gain in
      FC chickens was confirmed by the estimated lower fat deposition per kg W0.75 and
      by the lower fat: protein ratio.

PMID- 9649883
TI  - Quantification of a sperm-egg interaction for estimating the mating efficiency of
      broiler breeder flocks.
AB  - 1. The frequency distribution of points of sperm hydrolysis (or holes) produced
      per unit area of the inner perivitelline layer was examined in samples of
      approximately 60 laid eggs, taken on the same day from each of 19 flocks of
      broiler breeder hens. 2. The holes counted in samples of perivitelline layer from
      eggs varied from 0 to greater than 100; lower numbers being found in eggs from
      flocks with lower fertility. 3. The median frequency of holes in the inner
      perivitelline layer was strongly correlated (r = 0.92) with the median frequency
      of spermatozoa found trapped in the corresponding outer perivitelline layer. 4.
      The median frequency of holes in the inner perivitelline layer and of spermatozoa
      in the outer perivitelline layer were both strongly correlated (r = 0.80 and
      0.77, respectively) with flock fertility. 5. It is suggested that counting
      'holes' in the inner perivitelline layer of laid eggs is a more convenient method
      for assessing breeding efficiency and predicting flock fertility than counting
      spermatozoa trapped in the outer perivitelline layer.

PMID- 9649884
TI  - Evaluation of semen from individual male domestic fowl by assessment of sperm:
      perivitelline interaction in vitro and in vivo.
AB  - 1. Spermatozoa in semen samples from 8 individual male domestic fowls were shown
      to have a differential and characteristic ability to hydrolyse holes in the inner
      perivitelline layer from laid eggs in an in vitro assay. 2. The number of holes
      produced by samples of spermatozoa per unit area of inner perivitelline layer in
      vitro was linearly correlated with sperm ATP content (r = 0.85) and motility (r =
      0.76). 3. The number of holes formed in the inner perivitelline layer in vitro
      was also linearly correlated with the numbers of holes formed in the inner
      perivitelline layer of eggs fertilised in vivo, in inseminated hens (r = 0.90);
      and was correlated logarithmically with the proportion of fertile eggs laid by
      these hens.

PMID- 9649885
TI  - Effects of age at onset of production, light regime and dietary calcium on
      performance, eggshell traits, duodenal calbindin and cholecalciferol metabolism.
AB  - 1. Rate of production and shell thickness (ST) decreased, while body weight (BW),
      egg weight (EW) and percentage breakage increased progressively with age. Shell
      weight (SW) increased until 8 to 13 months of age and then decreased. 2. Early
      onset of production resulted in lower BW and EW at the onset of production, and
      lower pooled averages of BW, EW, SW and ST, as compared with late or medial onset
      of production. In 4 out of 5 trials, early onset did not result in the production
      of more eggs during the laying period. 3. Early onset of production is associated
      with physiological Ca deficiency as indicated by increases in kidney-1
      hydroxylase and duodenal calbindin in early layers as compared with late layers.
      Early layers exhibited a more severe reduction in shell quality as the result of
      Ca deficiency as compared with late layers. 4. Feeding pullets with a prelaying
      diet containing 3.9% Ca did not affect unequivocally the performance or shell
      quality during the whole productive period, whether the birds started to lay
      early or late. The dietary treatment did not cause renal damage, as indicated by
      morphological examination and by plasma calcium and uric acid concentration.

PMID- 9649886
TI  - Comparative development of the ovary and production, fertility and hatchability
      of eggs from traditional turkeys and a contemporary male-line fed ad libitum or
      restricted.
AB  - 1. Ovarian function was assessed at first egg and at 44 and 54 weeks of age in
      traditional turkeys and in a male-line fed ad libitum or restricted to 0.5 of ad
      libitum during rearing. Egg production was recorded daily and fertility and
      hatchability were determined at 2 ages. 2. Age at sexual maturity did not differ
      between the 3 treatments. 3. The number of follicles at first egg in the male
      line averaged 16.3 compared with 8.9 in traditional turkeys. Food restriction in
      the male line decreased the number of yellow follicles to 14.6 at first egg and
      restricted birds were largely in a non-reproductive state from 44 to 54 weeks of
      age. 4. The total number of recorded ovipositions to 54 weeks of age in male line
      fed ad libitum or restricted and traditional turkeys respectively were 40.1, 25.2
      and 70.7; comparable productions of normal shelled eggs were 28, 20 and 66.3. 5.
      There were no differences between treatments in fertility after a single
      insemination at 2 different ages. Hatch of fertiles after the first inseminations
      were 71.4, 45.5 and 90.3 respectively for male line fed ad libitum or restricted
      and traditional turkeys.

PMID- 9649887
TI  - Establishing a medical research agenda for child sexual abuse. Historical
      perspective and executive summary.

PMID- 9649888
TI  - It's time to broaden the agenda.

PMID- 9649889
TI  - Epidemiology of sexual abuse of children: old problems, new directions.
AB  - Over the last 2 decades, the science of epidemiology has made important
      contributions to the understanding of sexual abuse of children. Well-designed
      epidemiological studies conducted during the next two decades should help refine
      our knowledge of the frequency of the problem, as well as further our
      understanding of risk factors and consequences.

PMID- 9649890
TI  - Prevalence, risk, sensitivity, and specificity: a commentary on the epidemiology
      of child sexual abuse and the development of a research agenda.

PMID- 9649891
TI  - Triage and referrals for child sexual abuse medical examinations from the
      sociolegal system.

PMID- 9649892
TI  - Triage and referrals for child sexual abuse medical examinations: which children
      are likely to have positive medical findings?

PMID- 9649893
TI  - Behavioral manifestations of child sexual abuse.

PMID- 9649894
TI  - Medical consequences of child sexual abuse.

PMID- 9649895
TI  - Technical conduct of the child sexual abuse medical examination.

PMID- 9649896
TI  - Further technical considerations regarding conducting and documenting the child
      sexual abuse medical examination.

PMID- 9649897
TI  - Emotional impact of the medical examination for child sexual abuse.

PMID- 9649898
TI  - Children's responses to the medical evaluation for child sexual abuse.

PMID- 9649899
TI  - Normal anogenital anatomy.

PMID- 9649900
TI  - The appearance of acute, healing, and healed anogenital trauma.

PMID- 9649901
TI  - The transmissibility of sexually transmitted diseases in sexually abused
      children.

PMID- 9649902
TI  - Impact of child sexual abuse medical examinations on the dependency and criminal
      systems.

PMID- 9649904
TI  - Quantitative digital evaluation of myocardial exercise thallium-201 single-photon
      emission tomography in post-menopausal women.
AB  - Quantitative computerized analysis of data from myocardial thallium-201 (201Tl)
      single-photon emission tomography (SPET) may improve the diagnostic accuracy of
      coronary heart disease. The reference ranges for post-menopausal women are,
      however, limited and obtained mainly from patients. To compare reference values
      from healthy post-menopausal women and to improve the quantitative analysis, 20
      women (10 patients with coronary heart disease and previous infarction and 10 age
      matched healthy volunteers) were examined immediately post exercise and after a
      delay. A nine-segment 'bull's-eye' model was used for analysis. At visual
      evaluation, reproducibility was high (93%), no false-positive results were
      obtained and in 70% of the patients the SPET was interpreted as abnormal. Using
      reported reference values for quantitative analysis, all the healthy women had an
      abnormal result. New reference values based on three different methods of
      'normalization' were calculated: the relative activity of segment 3 set to 100%,
      the segment with the highest activity set to 100% and a least-squares method.
      They all differed significantly from those that had previously been reported. The
      frequencies of agreement between visual and quantitative analysis were 84-92% and
      were highest when segment 3 was used as a reference, but in this case only 40% of
      the patients with coronary heart disease had an abnormal SPET. Using the least
      squares method for handling digital information, the SD of the normal values
      decreased and 90% of the patients with coronary heart disease were accurately
      diagnosed. These results provide quantitative digital reference values for
      healthy post-menopausal women. They verify that quantitative analysis is in
      diagnostic agreement with visual evaluation, stress the need for local
      verification of reference ranges and suggest a least-square normalization method
      for the analysis.

PMID- 9649905
TI  - Electrocardiographic changes during prolonged coronary artery occlusion in man:
      comparison of standard and high-frequency recordings.
AB  - Detection of acute myocardial ischaemia using electrocardiographic methods is
      generally based on assessment of the ST segments in the standard 12-lead
      electrocardiogram (ECG). Several studies have also shown changes in high
      frequency QRS components during acute ischaemia. The purpose of the present study
      was to determine the changes in high-frequency QRS components during prolonged
      percutaneous transluminal coronary angioplasty (PTCA) and to compare these
      changes with ST-segment deviations in the standard 12-lead ECG. The study
      population consisted of 19 patients receiving prolonged PTCA. Standard and high
      resolution signal-averaged ECGs were recorded before and during balloon
      inflation. The high-resolution recordings were performed using bipolar X, Y and Z
      leads. The QRS complexes in the high-resolution signal-averaged ECGs were
      analysed within a bandwidth of 150-250 Hz. During inflation, significant
      reductions in high-frequency QRS components were observed (12-72%). Changes in
      the high-frequency QRS components were seen in four of the patients without ST
      segments deviation in the standard ECG. The correlation between the ST-segment
      deviation and the reduction in high-frequency QRS components was weak (r = 0.27).
      Acute coronary artery occlusion produces changes in high-frequency QRS
      components, even in the absence of ST-segment deviation in the standard ECG.
      Further studies need to be carried out to evaluate whether analysis of high
      frequency QRS components could provide a method for detecting myocardial
      ischaemia and give additional information to that available in the ST segment in
      the standard ECG.

PMID- 9649906
TI  - Poor reproducibility of exercise test in assessment of claudication.
AB  - To assess reproducibility of the exercise test in intermittent claudication, a
      prospective, comparative, randomized study was undertaken. Ten patients with
      stable intermittent claudication of ischaemic origin were exercised on a flat
      surface (0-Ex), with 12% steady inclination (12-Ex) and with progressively
      increasing inclination (p-Ex) in a random order during three different sessions.
      The ankle-brachial index (ABI) at rest and after exercise (rABI, exABI), initial
      and maximum walking distance (IWD, MWD) and metabolic equivalent (MET) were
      obtained as the main outcome measures. The results were analysed using
      intraindividual coefficients of variation (CVs) and standard deviations (SDs).
      The ABI values of the worst extremity were used in evaluation of results.
      Reproducibility of the exercise ABI appeared to be good, especially during
      progressively increasing exercise, the mean CV being 9 +/- 5%. The best mean CV
      was observed during p-Ex (16% +/- 14%) for maximum walking distance. The mean CV
      for initial walking distances ranged from 30% to 54%. Treadmill exercise testing
      to measure walking distances is highly inaccurate and the value of exercise on
      the flat treadmill should be questioned. Graded exercise appeared to be the most
      reproducible in this respect. The ABI after exercise, however, was a reliable
      single parameter when assessing arterial insufficiency causing decreased walking
      capacity.

PMID- 9649907
TI  - Reduced left ventricular relaxation velocity after acute myocardial infarction.
AB  - Diastolic left ventricular function is usually described using Doppler recording
      of the early to atrial (E/A) ratio. However, because of pseudonormalization in
      patients with moderately impaired diastolic function, the E/A ratio does not
      allow a meaningful comparison between a group of patients with varying degrees of
      dysfunction, e.g. after acute myocardial infarction (AMI), and a group of healthy
      control subjects. In this study, diastolic function was assessed using the E/A
      ratio, deceleration time of early mitral inflow and maximal longitudinal
      relaxation velocity. The relaxation velocity was measured using echocardiographic
      M-mode recording of mitral annulus motion. Mitral annulus motion was recorded in
      four- and two-chamber views. Relaxation velocities were measured in the septal,
      lateral, anterior and posterior parts of the mitral annulus and the mean value
      (RVm) was calculated. Twenty-two consecutive patients were investigated 3-21 days
      after first transmural AMI. Twenty-two healthy subjects of similar age served as
      a control group. The group of patients with AMI had an RVm of 40.9 +/- 15.4 mm s
      1 compared with 68.5 +/- 12.4 mm s-1 in the control group (P < 0.0001). In
      contrast, the E/A ratio, deceleration time and heart rate did not differ
      significantly between the two groups. The results suggest that maximal
      longitudinal relaxation velocity is a simple and appropriate measure of diastolic
      function in patients with transmural AMI.

PMID- 9649908
TI  - High blood pressure and muscle morphology/metabolism--causal relationship or only
      associated factors?
AB  - As muscle tissue constitutes a main target organ for glucose metabolism and is
      responsible for the development of insulin resistance, it seems plausible to
      elucidate the relationship between blood pressure and muscle morphology and
      metabolism. The association between blood pressure and capillarization/morphology
      of the vastus lateralis muscle and metabolic variables was evaluated in 24
      perimenopausal obese women [body mass index (BMI) 34.9 +/- 1.1; waist-hip ratio
      (WHR) 0.90 +/- 0.02]. The muscle enzyme activity of lipoprotein lipase (LPL),
      citrate synthase and glycogen synthase was determined. There was a significant
      negative correlation between the percentage of type I fibres and relative fibre
      area of type I on the one hand and systolic and diastolic blood pressure on the
      other. There was a negative correlation between the capillary density (i.e.
      number of capillaries/muscle fibre) and a positive correlation between the
      diffusion distance (fibre area supplied by one capillary) and diastolic blood
      pressure. The activities of LPL and citrate synthase were positively correlated
      with the percentage of type I and negatively correlated with the percentage of
      type II muscle fibres. The activity of LPL was also negatively correlated with
      plasma glucose and the insulin/C-peptide ratio. The insulin/C-peptide ratio was
      positively correlated with the percentage of type II muscle fibres. In stepwise
      multiple regression analyses, 20-30% of the variation in systolic and diastolic
      blood pressure could be explained by the variables of muscle fibre distribution.
      Excluding muscle morphological variables from the regression model, the insulin/C
      peptide ratio accounted for 13% of the variation in systolic and diastolic blood
      pressure. The results of the study show the close association between muscle
      morphology and blood pressure. It remains to be elucidated whether this
      association indicates a causal relationship.

PMID- 9649909
TI  - Office and laboratory blood pressures as predictors of daily blood pressure level
      in normotensive subjects and borderline and mild hypertensive subjects.
AB  - A series of standardized laboratory tests [10 min sitting and supine, 9 min
      standing, dynamic; cycle ergometer (ERG) and isometric exercise; handgrip (HG)]
      were performed during intra-arterial blood pressure (BP) recording in 97 healthy
      unmedicated men, initially classified as normotensive (NT, n = 34), borderline
      hypertensive (BHT, n = 29) or mildly hypertensive (HT, n = 34) by repeated office
      blood pressure (OBP) measurements. After testing, a 24-h intra-arterial
      ambulatory BP (IABP) recording was obtained while subjects performed their normal
      activities. Day and night periods were analysed as well as 24-h averages for
      systolic BP (SBP) and diastolic BP (DBP) using Pearson correlations and multiple
      linear regressions. In normotensive subjects, the supine SBP predicted IABP
      measurements best (r range 0.39-0.69, P < 0.05-0.001). In multiple regression,
      supine SBP explained 49% of 24-h SBP variance (F = 12.4, P = 0.001). For BHT,
      supine SBP was also the best predictor (r range 0.09-0.64, P NS to P < 0.001),
      and it explained 37% of 24-h SBP variance (F = 15.6, P = 0.0005). In HT, ERG DBP
      correlated best with IABP (r range 0.52-0.75, P < 0.01-0.001). ERG SBP explained
      49% of 24-h SBP (F = 31.0, P = 0.0000) and ERG DBP explained 56% of 24-h DBP (F =
      35.4, P = 0.0000) variance. Laboratory BP correlations were generally better with
      day than with night measurements. OSBP correlated moderately well with IABP in
      NT, and weakly in BHT and HT; ODBP instead correlated with IABP in NT and HT but
      not significantly in BHT. In conclusion, OBP is less closely related to IABP than
      laboratory BP, but even laboratory BP generally explains less than 50% of IABP
      variance. Stressors such as exercise are useful only in HT. For BHT, the
      prediction of IABP with laboratory measures was even weaker than in other groups,
      and thus ambulatory measurements cannot be replaced by short-duration laboratory
      measurements and stress tests.

PMID- 9649910
TI  - Reproducibility of oximetry with a static charge-sensitive bed in evaluation of
      obstructive sleep apnoea.
AB  - The reproducibility of overnight polygraphic recording with oximetry, the use of
      a static charge-sensitive bed (SCSB), thermistors and a body position sensor was
      assessed in diagnosing obstructive sleep apnoea syndrome (OSAS). Forty-six
      patients with a clinical suspicion of OSAS underwent a repeat recording. No
      treatment for OSAS and no change in patient characteristics was allowed between
      duplicate nights. Between repeated recordings significant correlations were found
      for ODI4, time spent at SaO2 < 90% and the mean nadir SaO2. Good agreement was
      found in concordance of classification of ODI4, time spent at SaO2 < 90% and body
      movements. The combination of oximetry, thermistors, SCSB and body position
      sensor has a good reproducibility as an affordable screening method in the
      evaluation of OSAS.

PMID- 9649911
TI  - Breathing efficiency during inspiratory threshold loading in patients with
      chronic obstructive pulmonary disease.
AB  - Patients with chronic obstructive pulmonary disease (COPD) demonstrate an
      increased oxygen cost of breathing. It is as yet unclear whether this is related
      to a decreased breathing efficiency. The aim of the present study was to compare
      breathing efficiency in 16 patients with COPD (11 men, five women) and 16 healthy
      elderly subjects (seven men, nine women), and to investigate a possible
      relationship between breathing efficiency and resting energy expenditure (REE).
      REE was measured using a ventilated hood system. Breathing efficiency was
      assessed by measuring oxygen consumption (V'O2), mean inspiratory mouth pressure
      (MIP) and flow during breathing at rest and subsequently during breathing against
      an inspiratory threshold (40% of maximal inspiratory pressure). During loaded
      breathing there was a significant increase in V'O2, MIP, and external work of
      breathing compared with unloaded breathing in both groups. As intended,
      ventilation did not increase significantly during the breathing efficiency test
      in the patients with COPD. The breathing efficiency (median, range) of the
      patients with COPD was similar (3.7%, 1.4-8.7%) to that of the healthy elderly
      subjects (3.2%, 1.7-8.3%). Breathing efficiency was not correlated with REE in
      either group. In the present study, in which dynamic hyperinflation was probably
      prevented, no difference in breathing efficiency was found between healthy
      elderly subjects and COPD patients when breathing against an external inspiratory
      threshold. Furthermore, breathing efficiency was not related to REE in both
      groups.

PMID- 9649912
TI  - Divergent cardiac response to exercise in essential hypertension vs. normotension
      and the effect of enalapril.
AB  - The aims of this study were to examine (1) the cardiac response to exercise in
      essential hypertension and (2) the effect of long-term enalapril treatment on
      cardiac reserve. Ten normotensive control subjects and 15 patients with moderate,
      essential hypertension underwent radionuclide ventriculography during graded,
      supine exercise (0 W-50 W-100 W). The hypertensive patients were studied during
      monotherapy using hydrochlorothiazide and 3 and 12 months after supplementation
      with enalapril 10-40 mg o.d. During exercise, the control subjects demonstrated a
      17% increase in left ventricular ejection fraction (LVEF) mediated by a 30%
      decrease in end-systolic volume, a small increase in stroke volume and a minor
      biphasic (increase-decrease) change in end-diastolic volume. In the hypertensive
      patients, both the end-diastolic and the end-systolic volume increased
      substantially with no increase in LVEF, although stroke volume increased by 33%.
      Long-term therapy with enalapril induced only a minor change towards a more
      normal pattern of cardiac response to exercise. The hypertensive patients
      increased their stroke volume during exercise by recruiting preload reserve
      instead of increasing contractility. Long-term treatment with enalapril had
      little, if any, effect on this abnormal cardiac response.

PMID- 9649913
TI  - Oral contraception and other factors in relation to hospital referral for
      fracture. Findings in a large cohort study.
AB  - There is good evidence that estrogens and progestogens have an important effect
      on bone metabolism. This article explores the relationship between oral
      contraceptive (OC) use and fractures occurring at various sites among the 17,032
      participants in the Oxford-Family Planning Association contraceptive study, which
      now includes information accumulated during 310,000 woman-years of observation
      between 1968 and 1994. In total, 1308 women suffered at least one fracture during
      the follow-up period, which was largely confined to premenopausal years. When all
      fractures were combined, there was a modest, but highly significant trend (p <
      0.001) of increasing risk with total duration of oral contraceptive use. In
      addition, there was statistically significant heterogeneity (p < 0.01) when
      overall fracture rates were examined in relation to recency of oral contraceptive
      use during the premenopausal lifespan. The highest relative risk (1.3, 95% CI 1.1
      1.5) was for current or recent oral contraceptive users; however, viewed as a
      whole, no clear pattern of risk was apparent. Examination of the data for
      individual fracture sites (including the lower end of the radius/ulna) did not
      provide any evidence of a protective effect of oral contraceptive use. These
      results are closely similar to those reported from the Royal College of General
      Practitioners Oral Contraception Study in 1993.

PMID- 9649914
TI  - Depressive symptoms and Depo-Provera.
AB  - Women enrolled in a multicenter prospective study were evaluated to identify any
      possible relationship between depressive symptoms and the use of contraceptives.
      Women choosing Depo-Provera (n = 495) were evaluated before starting these
      contraceptives and were reinterviewed 1 year later. Women who continued the
      method had lower depressive symptom scores at baseline than did the women who
      discontinued the method or who were lost to follow-up. Among the continuing Depo
      Provera users, the depressive symptom scores improved slightly at 1 year (7.4 vs
      6.7). Those subjects with the highest (i.e., worst) scores at enrollment
      demonstrated improved scores at follow-up.

PMID- 9649915
TI  - Depressive symptoms and Norplant contraceptive implants.
AB  - Women enrolled in a multicenter prospective study were evaluated to identify any
      possible relationship between depressive symptoms and the use of contraceptive
      implants. Women choosing Norplant implants (n = 910) were evaluated before
      starting this contraceptive and were reinterviewed at 6 months and 2 years. Women
      who continued the method had lower depressive symptom scores before initiating
      Norplant implants than did the women who discontinued the method or who were lost
      to follow up. Among the continuing Norplant implant users, the mean scores were
      similar before starting Norplant and at 6 months (7.9 vs 7.7). The strongest
      overall predictor of the depressive symptom score was relationship satisfaction.
      At 24 months, the subgroup of continuing users with decreased relationship
      satisfaction had an increase in depressive symptom score, but those with stable
      or improved relationships had stable depressive symptom scores. The subjects with
      the highest (i.e., worst) scores at enrollment demonstrated improved scores
      during follow-up. These results are reassuring for women who are concerned that
      Norplant use may adversely affect their mood.

PMID- 9649916
TI  - Oral contraceptive use before and after the latest pill scare in The Netherlands.
      Changes in oral contraceptive use and how users change.
AB  - In October 1995, a "pill scare" developed in Europe. In the Netherlands, the
      recommendations given were 1) to not alarm women without risk for deep vein
      thrombosis (DVT), and 2) to be reserved in prescribing third generation oral
      contraceptives (OC) for young women who were beginning OC use. To determine
      whether there is a change in the prescription of third generation OC after the
      latest pill scare, prescription data from 1/10/94 to 1/10/96, covering a
      population of +/- 120,000 persons, were studied with respect to OC use before and
      after the pill scare. Trend analyses revealed a significant decline in third
      generation compared with total OC prescribing only in the youngest age category
      (p = 0.0034). Further, switch behavior was studied. Switches from third to second
      generation OC were more prevalent after the pill scare than before (odds ratio =
      2.63; 95% confidence interval 1.84-3.75) and switches from second to third
      generation OC were significantly less prevalent after the pill scare. This
      indicates that Dutch prescribers have reacted to the pill scare in the way that
      the government recommended.

PMID- 9649917
TI  - Perforations with intrauterine devices. Report from a Swedish survey.
AB  - This survey comprised 50 consecutive perforations occurring with intrauterine
      devices (IUD) reported to the National Patient Insurance Scheme Register during
      1990 to 1993. All 50 women were parous and > 20 years of age at the time of IUD
      insertion. Forty-two (84%) of the IUD were inserted by a midwife and eight by a
      gynecologist. A total of 45 women (90%) had their IUD inserted < 1 year after a
      full-term pregnancy and 31 women (62%) had their IUD inserted < or = 12 weeks
      after delivery. Of the 50 women, 27 (54%) reported that they were breastfeeding
      at the time of IUD insertion. No particular IUD was overrepresented in relation
      to its share on the market. In 31 cases (62%), severe pain at insertion and
      during the first 24 h was recorded. In 14 women (28%), the perforation was
      diagnosed early (i.e., within 1 month of insertion) and in 36 women (72%), the
      perforation was diagnosed > 1 month after insertion. Lower abdominal pain was the
      most frequent symptom at early diagnosis but in two cases, the main symptom was
      heavy bleeding. Among the 36 women in whom the perforation was discovered more
      than 1 month after insertion, the diagnosis was made when an unexpected pregnancy
      occurred in 20 women (56%). In 15 cases, the IUD strings were not visible during
      pelvic examination at a routine check-up, which led to efforts to locate the IUD.
      Thirty-two women (64%) underwent laparotomy for removal. We conclude that
      lactating women seem to be a risk group for perforation and that a national
      register of IUD perforations could provide a better means of quality control.

PMID- 9649918
TI  - Identification of choriocarcinoma by the hCG beta-to-hCG proportion in patients
      with delayed diagnosis caused by contraceptive use.
AB  - The use of contraceptives, especially subdermal implants and levonorgestrel
      containing intrauterine device (IUD), often cause irregular bleeding. Thus, they
      may mask unsuspected choriocarcinoma, which also often presents with abnormal
      bleeding. Choriocarcinoma is mostly curable with combination chemotherapy, but
      delayed diagnosis can lead to treatment failure. Two cases of choriocarcinoma
      with considerable delay in diagnosis, due partly to contraceptive use, are
      reported. The proportion of human chorionic gonadotropin-beta (hCG beta) and
      total hCG immunoreactivity showed that the proportion of hCG beta was elevated at
      presentation in both cases.

PMID- 9649919
TI  - Tamoxifen-induced light and electron microscopic changes in the rat testicular
      morphology and serum hormonal profile of reproductive hormones.
AB  - The effects of oral administration of tamoxifen at doses of 40 and 200
      micrograms/kg/day on testicular histology, testicular ultrastructure and serum
      hormonal profile were studied. The drug was administered to adult male rats over
      a period of 90 days and the effect was assessed at 10-day intervals. The
      morphometry, microscopic structures of the testis, including ultrastructure and
      daily sperm production rate, were evaluated. The hormone profiles of luteinizing
      hormone (LH), follice-stimulating hormone (FSH), testosterone, and estradiol were
      studied. The testes from treated animals showed disorganization of tubular
      elements with increased intercellular space. At day 50, the changes were
      extensive including presence of phagosomes. Morphometric studies showed a
      reduction in the spermatid and spermatozoan population (69.3%) with no changes in
      tubular diameter. The mean Leydig cell area was significantly lowered at day 50,
      at both doses. The daily sperm production rate was reduced as compared with
      controls. An array of degenerative changes were revealed by ultrastructural
      studies. The changes were extensive at day 50 at both doses. The characteristic
      features were lost in most of the cells with phagolysosomes becoming abundant.
      The cytoplasm of the cells was dense with poorly defined cytoplasmic organelles.
      Circulating LH levels were not modified at the 40 micrograms/kg/day dose but at
      200 micrograms/kg/day, LH levels were significantly decreased. Initial transitory
      rise in FSH was seen with both doses. Both doses of tamoxifen decreased
      testosterone levels. Changes in the circulating estradiol levels were
      inconsistent, and no apparent relationship between dose and days of treatment was
      observed. Thus, this study supports our thesis of tamoxifen as a potential male
      contraceptive agent.

PMID- 9649920
TI  - Long-term sequelae of tolnidamine on male reproduction and general body
      metabolism in rabbits.
AB  - The long-term effects of tolnidamine on male reproduction and general body
      metabolism were studied in rabbits (Oryctolagus cuniculus). The study was divided
      into three groups of 10 animals each. The first group (A) received vehicle alone
      to serve as controls. The second and third groups (B and C) of animals were
      administered tolnidamine orally at 50 mg/kg body weight/week and 50 mg/kg body
      weight/day, respectively, for a period of 150 days. The animals of group B
      exhibited a sperm density of 23.60 million/mL +/- 4.87 million/mL (vs 453.00
      million/mL +/- 65.30 million/mL in group A) after 150 days of treatment. In group
      C, all animals were azoospermic after 135 days of treatment. A reversible
      impairment of sperm motility, vitality and morphology was noticed. Semen weight,
      volume, color, pH, libido, and circulatory levels of testosterone remained
      unchanged. In group B animals, sperm density did not return to control levels
      even at 150 days after cessation of treatment (37.40 million/mL +/- 4.46
      million/mL, vs 380.00 +/- 40.80 million/mL in group A). However, spermatozoa
      reappeared in animals treated daily (group C) after 30 days of recovery but
      remained < 5 million/mL during the entire recovery period. A reversible,
      significant depletion was recorded in seminal glycerylphosphorylcholine (GPC)
      levels. Fertility was unimpaired in group B animals when compared with those in
      group A. In group C, fertility was reduced to zero after 150 days of treatment
      and at 90 days and 150 days after cessation of treatment. No significant
      alterations were observed in other semen biochemical, hematologic, or blood/serum
      biochemical parameters with either dose regimen. It is concluded that tolnidamine
      administration induced dose dependent, irreversible inhibition of sperm
      production without altering general body metabolism in male rabbits.

PMID- 9649921
TI  - c-fos protein expression in apoptotic rat spermatocytes induced by gossypol.
AB  - Proto-oncogene products such as c-fos protein with a molecular weight of 62 kDa
      have been identified in rat spermatocytes. In this study, cellular levels of c
      fos proteins in spermatocyte, either with or without gossypol exposure, were
      quantitatively detected by Western immunoblot and a computer-controlled Spot
      denso-program with an IS-1000 Digital Imaging System. Within 0.5-3.5 h (an
      average of 2 h) of the addition of gossypol, levels of c-fos proteins fell
      dramatically. The reduction in c-fos proteins occurred 6 h before the apoptosis
      of spermatocytes in the presence of gossypol. Four hours after exposure to
      gossypol, the c-fos protein content was overexpressed. The period of c-fos up
      regulation lasted for approximately 8 h. The increase in c-fos protein coincided
      with a high rate of apoptotic cell death. Morphologic structure of the dying cell
      was revealed by electron microscopy. These results suggest that spermatocyte
      apoptosis induced by gossypol correlates with biphasic c-fos protein-mediated
      apoptosis.

PMID- 9649922
TI  - Growth response of human coronary smooth muscle cells to angiotensin II and
      influence of angiotensin AT1 receptor blockade.
AB  - BACKGROUND: The renin-angiotensin system has been implicated in the development
      of vascular wall thickening in cardiovascular disease, through the growth
      promoting actions of the vasoconstrictive agent, angiotensin II, on vascular
      smooth muscle cells. OBJECTIVE: To investigate the effect of angiotensin II on
      growth of human coronary artery smooth muscle cells (cSMCs) in culture, and to
      identify the angiotensin receptor(s) mediating such a response. METHODS: Human
      cSMCs were isolated from coronary arteries of recipient hearts obtained during
      transplantation, and characterized by immunohistochemistry. The effect of
      angiotensin II on protein synthesis by cSMCs was measured by [3H]leucine
      incorporation and protein concentration assays. Human cSMC proliferation was
      assessed by [3H]thymidine incorporation assay and cell count. Reverse
      transcriptase polymerase chain reaction (RT-PCR) was used to detect angiotensin
      receptor expression. Transient increases in intracellular calcium concentration
      in cSMCs in response to angiotensin II stimulation were visualized under fura-2
      fluorescence microscopy. RESULTS: Angiotensin II (1 nmol/l-10 mumol/l) stimulated
      protein synthesis in cSMCs (maximum 24 +/- 2% increase in incorporation of
      [3H]leucine over 48 h; n = 4, P < 0.01). An increase in cellular protein content
      was also measured. However, angiotensin II had no effect on proliferation of
      quiescent cSMCs. The increased protein synthesis was completely inhibited by
      pretreatment with the angiotensin AT1 receptor antagonist, losartan, but not the
      AT2 receptor antagonist, PD123319. Expression of the angiotensin AT1 receptor
      subtype was detected in cSMCs by RT-PCR. Angiotensin II stimulation of cells
      triggered transient increases in intracellular calcium concentration, which were
      abolished by losartan, but were insensitive to PD123319 and pertussis toxin.
      CONCLUSIONS: The results of this study in human coronary VSMCs indicate that
      angiotensin II and the AT1 receptor may be involved in the development of
      coronary artery disease in man.

PMID- 9649923
TI  - Pathogenetic implications of hyaluronan-induced modification of vascular smooth
      muscle cell fibrinolysis in diabetes.
AB  - BACKGROUND: Proteolysis, modulated in part by intramural fibrinolytic system
      proteins and their inhibitors, appears to influence vascular smooth muscle cell
      (SMC) migration and proliferation and remodeling of extracellular matrix (ECM).
      Alterations of fibrinolysis in circulating blood and of proteolysis within vessel
      walls in experimental animals and patients with diabetes have been associated
      with accelerated vascular disease. Hyaluronan, a prominent component of ECM in
      normal vessels, is increased in the tunica media of macroscopically normal
      arterial vessels from patients with type 2 diabetes. OBJECTIVE: To determine
      whether hyaluronan alters the expression of the fibrinolytic system protein,
      plasminogen activator inhibitor type-1 (PAI-1), in human vascular SMCs, thereby
      potentially accelerating vascular disease in patients with type 2 diabetes.
      METHODS: Urokinase-type and tissue-type plasminogen activators (uPA and tPA) and
      PAI-1 were assayed in vascular SMC conditioned media and in cell lysates, using
      enzyme-linked immunosorbent assay and western blotting. RESULTS: Hyaluronan
      increased the 24-h release of PAI-1 into conditioned media in a concentration
      dependent and time-dependent manner (1.8-fold compared with control with 1 mg/ml
      hyaluronan; n = 9, P < 0.01). Although the accumulation of uPA in conditioned
      media tended to increase also, uPA content was reduced in cell lysates (64% of
      control with 0.1 mg/ml hyaluronan at 24 h; n = 9, P < 0.01) without any change in
      PAI-1. Concentrations of tPA in conditioned media and cell lysates were
      unchanged. Digestion of hyaluronan with hyaluronidase (50 turbidity reducing
      units (TRU)/ml) or exposure of the smooth muscle cells to antihuman CD44 antibody
      (1 microgram/ml) that binds to the hyaluronan cell surface receptor obviated the
      effects of hyaluronan. CONCLUSION: Our results indicate that increases in
      hyaluronan increase vascular SMC expression of PAI-1, a phenomenon that may alter
      the balance between proteolysis and its inhibition in vessels of patients with
      type 2 diabetes, thereby contributing to the acceleration of macroangiopathy.

PMID- 9649924
TI  - Influence of the culprit lesion on clinical symptoms of coronary artery disease,
      with special emphasis on exercise data.
AB  - BACKGROUND: Clinical symptoms have been found to correlate only poorly with the
      severity of the culprit lesion in coronary artery disease. The purpose of the
      present study was to evaluate the influence of the culprit lesion and its change
      during exercise on clinical symptoms in patients with this condition. METHODS:
      Minimal luminal area was determined using biplane quantitative coronary
      angiography in 42 patients (aged 53 +/- 8 years) with coronary artery disease.
      Percent diameter stenosis and minimal luminal area and its change during exercise
      were assessed in all patients and compared with clinical symptoms judged
      according to the functional classification of the New York Heart Association
      (NYHA). Coronary dimensions were determined with the patient at rest, during
      supine bicycle exercise and after sublingual administration of 1.6 mg glyceryl
      trinitrate. RESULTS: Exercise-induced vasoconstriction of the culprit lesion was
      found in all patients (-14.0% at 102 W), but there was exercise-induced
      vasodilatation in the normal vessel segments (+13.0%). However, only minimal
      vasoconstriction was found in groups 1 (NYHA I: -0.5%, NS) and 2 (NYHA II: -4.7%,
      NS), but significant constriction in groups 3 (NYHA II-III: -18.0%, P < 0.01) and
      4 (NYHA III: -31.4, P < 0.01). Vasodilatation of the normal vessel segments was
      similar in the four groups. The observed inverse relationship between exercise
      induced changes in minimal luminal area and NYHA classification was stronger than
      the relationship between NYHA and minimal luminal area when the patient was at
      rest. There was no correlation between glyceryl trinitrate-induced vasodilatation
      and NYHA classification. CONCLUSIONS: The more severe the culprit lesion, the
      more pronounced the exercise-induced vasoconstriction. This effect of the culprit
      lesion was reflected by the clinical symptoms: the greater the exercise-induced
      vasoconstriction, the higher the NYHA classification. Thus the anatomy of the
      lesion (= severity) and the functional integrity of the endothelium (= exercise
      induced vasomotion) are two major determinants of clinical symptoms.

PMID- 9649925
TI  - Alterations in collagen subtype III and IV protein in experimental venous bypass
      grafting.
AB  - OBJECTIVE: To examine changes in collagen III and IV protein during the
      development of intimal hyperplasia in experimental vein grafts. METHODS: Sixteen
      New Zealand White rabbits underwent reversed, jugular vein, interposition
      grafting of the carotid artery. Vessels were harvested 3, 7 or 28 days after
      operation and subjected to immunohistochemical examination and gelatinase assays.
      RESULTS: In control vein, collagen IV was expressed around adventitial blood
      vessels and throughout the endothelium. Compared with its presence in control
      veins, collagen IV protein was decreased in the endothelium in all 3-day vein
      grafts and undetectable in the endothelium and intima in 7-day vein grafts, but
      was present in the endothelium and intimal hyperplasia in 28-day vein grafts. In
      contrast, collagen III was absent from the endothelium of control vein and 3-day
      vein grafts, was present at low levels in the intima of 7-day vein grafts, but
      was absent from the endothelium and intimal hyperplasia in 28-day vein grafts. In
      3-day vein grafts, areas of collagen IV loss colocalized to areas of leukocyte
      infiltration. Protein extracts from 3-day vein grafts contained a 72 kDa
      gelatinase. CONCLUSIONS: The presence and alterations of collagen protein in
      veins and vein grafts are subtype specific. Collagen III does not appear to be a
      normal component of intimal hyperplasia in vein grafts. The decrease in collagen
      IV protein in the endothelium of veins may be a component of the endothelial
      changes that follow bypass grafting, mediated by leukocytes, the induction of
      gelatinase activity, or both.

PMID- 9649926
TI  - QRS complex distortion predicts no reflow after emergency angioplasty in patients
      with anterior wall acute myocardial infarction.
AB  - BACKGROUND: In patients with acute myocardial infarction, distortion of the
      terminal portion of the QRS complex on the electrocardiogram (ECG) at the time of
      their admission to hospital is associated with larger final infarct size and
      greater mortality. This study assessed the results of emergency coronary
      angioplasty in patients with anterior acute myocardial infarction with and
      without distortion of the terminal portion of the QRS complex on the admission
      ECG. METHODS: We assessed the Thrombolysis in Myocardial Infarction (TIMI) trial
      flow grade, resolution of ischemic ECG changes, and clinical outcome after
      emergency angioplasty for acute anterior wall myocardial infarction in patients
      with (n = 21) and without (n = 21) distortion of the terminal portion of the QRS
      complex on the admission ECG. RESULTS: Compared with patients without distortion
      of the terminal portion of the QRS complex on the admission ECG, those with
      distortion had a significantly lower incidence of TIMI flow grade 3 (52% compared
      with 84%, P < 0.05), lower rate of resolution of the ischemic ECG changes (33%
      compared with 84%, P < 0.005), and greater rate of mortality during their stay in
      hospital despite successful balloon angioplasty (19% compared with 0%, P < 0.05).
      CONCLUSIONS: In patients with anterior wall acute myocardial infarction,
      distortion of the terminal portion of the QRS complex on the admission ECG
      predicts a greater mortality rate and a greater incidence of reflow impairment
      after emergency angioplasty.

PMID- 9649927
TI  - Protective effect of nisoldipine on dipyridamole-induced myocardial ischemia:
      correlation with exercise electrocardiography.
AB  - BACKGROUND: Nisoldipine, a dihydropyridine calcium channel blocker with strong
      coronary dilatative action, is commonly used in the treatment of myocardial
      ischaemia; its beneficial effect on effort angina has been demonstrated by
      several previous reports. Infusion of dipyridamole in doses sufficient to provoke
      myocardial ischaemia in patients with significant coronary artery disease is used
      safely in imaging studies for diagnostic purposes. OBJECTIVE: To evaluate the
      potential effect of nisoldipine on dipyridamole-induced ischaemia and to compare
      the results with the effect of nisoldipine on exercise-induced ischaemia. METHOD:
      Twelve patients (10 men and two women, mean age 62 +/- 8 years) with significant
      coronary artery disease (at least 70% lumen reduction in at least one major
      coronary vessel) were selected for inclusion in the study. In accordance with the
      inclusion criteria, the patients exhibited an ischaemic diagnostic response to a
      multistage exercise electrocardiography stress test (> 0.15 mV ST segment
      depression compared with the resting electrocardiographic tracing) and to a
      dipyridamole-echocardiography test (transient left ventricular dyssynergy of
      contraction during infusion of dipyridamole up to 0.84 mg/kg over 10 min), after
      3 days' cessation of antianginal treatment. After treatment with oral nisoldipine
      (10 mg twice daily) was introduced, the patients repeated the two tests, within
      18 days of the first evaluation. RESULTS: The dipyridamole-echocardiography test
      was positive for ischaemia in 12 patients who were not receiving nisoldipine and
      in eight patients who were receiving the drug (100% and 67% respectively, P <
      0.05). In the eight patients who gave positive dipyridamole-echocardiography
      tests both with and without treatment, dipyridamole time (time to onset of
      dyssynergy during the test) increased from 7.9 +/- 2.9 min to 10.2 +/- 3.1 min (P
      < 0.01). In these patients, no significant changes were observed, at ischaemia,
      in the severity and extent of induced dyssynergy, evaluated as wall motion score
      index (each of 16 left ventricular segments scored from 1 = normal to 4 =
      dyskinetic) after treatment (score variations from baseline to ischaemia: 0.20 +/
      0.11 without nisoldipine and 0.16 +/- 0.06 with nisoldipine; NS). Variations in
      dipyridamole time (arbitrarily considered to be 15 min in the negative
      dipyridamole-echocardiography test) were significantly correlated with variations
      in exercise time (duration of exercise to exhaustion or diagnostic positive
      response on the electrocardiogram): r = 0.75 (P < 0.01). No significant
      differences were recorded in rate-pressure product (beats/min x mmHg x 100) at
      peak ischaemia between patients who were or were not receiving nisoldipine,
      during either the exercise electrocardiography stress test (233 +/- 36 with
      nisoldipine and 244 +/- 39 without nisoldipine; NS) or the dipyridamole
      echocardiography test (147 +/- 21 with nisoldipine and 133 +/- 30 without
      nisoldipine; NS). CONCLUSION: Nisoldipine treatment can protect from dipyridamole
      induced ischaemia, being associated with a longer stress time, and completely
      preventing the development of ischaemia in some patients. The therapy-induced
      changes in ischaemic threshold during the dipyridamole-echocardiography test
      correlate with variations in exercise tolerance.

PMID- 9649928
TI  - Indobufen compared with aspirin and dipyridamole on graft patency after coronary
      artery bypass surgery: results of a combined analysis.
AB  - BACKGROUND: Two prospective, randomized, double-blind clinical trials, performed
      in the UK and Italy, showed that indobufen, a reversible cyclo-oxygenase
      inhibitor, is as effective as, and safer than, a combination of aspirin with
      dipyridamole in preventing occlusion of saphenous vein coronary artery bypass
      grafts (CABG) 1 year after surgery. OBJECTIVE: To obtain, in a larger patient
      population, a more precise estimate of the possible differences in efficacy and
      safety between the two treatments. METHODS: We performed a combined analysis of
      the results of the two studies, based on the 1-year angiography data, on a total
      of 934 patients with 2258 saphenous vein distal anastomoses. RESULTS: Patients in
      the UK and Italy had similar baseline clinical characteristics. The analysis
      confirmed that there were no significant differences between the two treatment
      groups in the proportion of patients with one or more occluded grafts and in the
      proportion of occluded distal anastomoses. The combined analysis showed that the
      difference in response frequency (indobufen compared with aspirin and
      dipyridamole) was close to 0: 2.0% (95% confidence interval (CI) -4.2 to 8.2) in
      terms of patients, and 0.8% (95% CI -2.5 to 4.2) in terms of distal anastomoses.
      The 1-year incidence of postoperative major cardiovascular events was not
      statistically different between the treatment groups (19/694 indobufen compared
      with 25/678 aspirin and dipyridamole). CONCLUSIONS: Two multicentre CABG studies
      performed in different countries in patients with similar characteristics showed
      similar results in terms of graft patency. On the basis of the combined analysis,
      the two treatments can reasonably be considered to be equally effective in the
      prevention of graft occlusion.

PMID- 9649930
TI  - Bibliography. Current world literature.

PMID- 9649929
TI  - Warfarin reduces silent cerebral infarction in elderly patients with atrial
      fibrillation.
AB  - BACKGROUND: Atrial fibrillation is reportedly one of the risk factors of silent
      cerebral infarction. The Shiga Atrial Fibrillation Trial was conducted in five
      medical centers, to test the hypothesis that warfarin can prevent silent cerebral
      infarction in patients with atrial fibrillation. METHODS: Magnetic resonance
      images (MRI) were taken at the time of the patient's entry to the study and 1
      year later in 15 asymptomatic patients (74 +/- 4 years old) with atrial
      fibrillation who were randomly allocated to two treatment groups to receive or
      not receive warfarin. The frequency of hyperintensities on T2-weighted axis MRI
      was rated using a four-point scale in the periventricular and centrum semiovale
      areas. Total silent cerebral infarction scores were calculated at the sum of the
      scores on MRI. RESULTS: Silent cerebral infarction was seen in 14 (93%) of the 15
      patients with atrial fibrillation and a total of 109 silent cerebral infarction
      lesions were detected. The number of hyperintensities in the periventricular and
      centrum semiovale areas increased over the 1 year of study (P < 0.01). The
      increase in total score over 1 year was less in the warfarin-treated group (1.6
      +/- 0.7 compared with 5.4 +/- 0.9, P < 0.05). CONCLUSION: Anticoagulation therapy
      can be useful to prevent silent cerebral infarction in neurologically normal
      elderly patients with atrial fibrillation.

PMID- 9649931
TI  - Pregnancy after breast cancer. The relationship of pregnancy to breast cancer
      development and progression.

PMID- 9649932
TI  - Essential fatty acids: molecular and cellular basis of their anti-cancer action
      and clinical implications.

PMID- 9649933
TI  - Small cell lung cancer: current status of new chemotherapeutic agents.

PMID- 9649934
TI  - The role of adjuvant chemotherapy in the treatment of adult soft tissue sarcomas.

PMID- 9649935
TI  - Soluble and insoluble fiber influences on cancer development.

PMID- 9649936
TI  - The role of exercise testing and gas-exchange measurement in the prognostic
      assessment of patients with heart failure.
AB  - Functional impairment has long been recognized as an important factor in the risk
      paradigm among patients with heart disease. In chronic heart failure, this issue
      has been even more important in recent years because of the steady growth in the
      number of patients awaiting heart transplantation relative to the available pool
      of donor hearts. The use of gas-exchange techniques to assess patients with heart
      failure has attracted interest because these techniques provide a more precise,
      reproducible, objective, and physiologic expression of exercise tolerance.
      Numerous studies published in the 1990s demonstrate that maximal oxygen uptake
      (peak VO2) is an independent predictor of mortality in patients with heart
      failure. Achievement of a peak VO2 that is less than 14 mL/kg/min has been
      recognized as one of the relative indications for transplantation, because
      patients who achieve a measurement that is higher than 14 mL/kg/min have a 1-year
      mortality rate similar to that of patients who undergo transplantation (i.e., >
      90%). However, some debate exists regarding the optimal cutpoint that separates
      survivors from nonsurvivors, and studies have not consistently defined the timing
      of the test relative to optimization of medical therapy. It has also been debated
      which hemodynamic variables, at rest or during exercise, should be used in
      combination with peak VO2 to optimally stratify risk in these patients. This
      article reviews the applications of cardiopulmonary exercise testing in prognosis
      among patients with chronic heart failure.

PMID- 9649937
TI  - Changing the remodeling process in heart failure: basic mechanisms and laboratory
      results.
AB  - Heart failure continues to be a major source of death and disability, and
      concepts and understanding of the disorder continue to evolve. There is now
      widespread recognition that myocardial remodeling is an important driving force
      behind the progression of heart failure. Both scientists and clinicians strive to
      understand the remodeling process better. Several animal models have been helpful
      in this regard. Yet controversy and uncertainties persist regarding the
      fundamental mechanisms of cardiac remodeling. To appreciate better the
      contribution of diminished contractility to the syndrome of heart failure, a
      number of laboratories have studied isolated cardiac myocyte function, both in
      animal models and in humans with cardiomyopathy. Results have been mixed and
      contradictory. A consistent theme found in many studies, however, is that the
      cells assume a more elongated shape. There may or may not be concurrent
      incremental changes in myocyte transverse diameter, depending on the model under
      study. At least two groups have claimed that maximal contractile properties of
      myocytes isolated from human failing hearts and from animals with experimental
      heart failure are normal, but this may depend on where the cells are taken in
      reference to acute myocardial injury. There are some important model-specific
      considerations when interpreting the results of isolated myocyte studies.
      Nevertheless, such experiments reinforce the concept that structural changes
      during cardiac remodeling, including myocyte growth, deposition of collagen, cell
      dropout, and perhaps myocyte slippage, all contribute to the architectural
      changes in the geometry of the left ventricle. The quantitative contribution that
      each structural change makes is not yet entirely clear. Studies in humans suggest
      that myocyte elongation may be the dominant mechanism, but it cannot account for
      the disproportionate increase in chamber size relative to myocyte length.
      Therefore, myocyte slippage is likely making some contribution to cardiac
      remodeling. Whether the remodeling process can be reversed is currently a topic
      of great research interest. Preliminary data from studies of left ventricular
      assist devices and beta-adrenergic blockers suggest that attenuation of
      progression and perhaps even reversal of remodeling is possible.

PMID- 9649938
TI  - Ventricular remodeling and its prevention in the treatment of heart failure.
AB  - Ventricular remodeling refers to changes in left ventricular (LV) geometry, mass,
      and volume in response to myocardial injury or alterations in load. The extent of
      LV dilatation or remodeling after myocardial infarction (MI) or in patients with
      heart failure is a strong predictor of both morbidity and mortality. Based on
      these observations, it is clear that LV remodeling is a maladaptive process. Two
      classes of drugs appear to inhibit LV remodeling. A large amount of data support
      the use of angiotensin-converting enzyme (ACE) inhibitors to improve survival and
      to prevent progressive remodeling. In addition, recent studies suggest that beta
      adrenergic blockers have a beneficial effect on both survival and remodeling.
      These data support a causative role of the renin-angiotensin system and perhaps
      the sympathetic nervous system in this process. Thus, ACE inhibitors and possibly
      beta-blockers should be part of the pharmacologic regimen for the treatment of
      patients with LV dysfunction to prevent progressive LV remodeling.

PMID- 9649939
TI  - Genetic risk factors for myocardial infarction.
AB  - Myocardial infarction (MI) is a complex phenotype caused by interaction of a
      number of genetic and environmental factors. A genetic susceptibility to MI was
      observed in a familial aggregation and studies in twins. Advances in molecular
      genetics have led to identification of a number of potential genetic risk factors
      for MI, such as variants of genes involved in vascular homeostasis, thrombosis,
      and lipid metabolism. Functional variants of angiotensin-1-converting enzyme
      (ACE), beta-fibrinogen, plasminogen activator inhibitor-1,
      methylenetetrahydrofolate reductase, glycoprotein Illa, and many apolipoprotein
      genes are considered excellent candidate risk factors for MI. Interaction of the
      susceptibility genes with modifier genes, environmental factors, and conventional
      risk factors results in the final phenotype of MI. Understanding the complex
      interaction between these factors is expected to provide significant insights
      into the pathogenesis of MI and lead to development of genetic-based risk
      stratification, prevention, and treatment.

PMID- 9649940
TI  - Molecular aspects of myocarditis.
AB  - The mechanisms of pathogenesis of myocarditis have remained elusive. Despite the
      demonstration a decade ago that persistent viral infection of the myocardium
      occurred in many patients, a clear description of the pathologic progression has
      not been forthcoming. Over the past year, a number of studies have added to the
      data defining the crucial roles of cytokine expression in the myocardium and the
      aberrant induction of apoptosis. Further, a mouse model of myocarditis resulting
      from the myocardial expression of tumor necrosis factor-alpha has been described.
      In addition, the identification of the common coxsackievirus B and adenovirus
      receptor has offered an explanation for the puzzling observation that these
      highly distinct virus types both cause cardiac disease. Finally, the near
      eradication of endocardial fibroelastosis associated with persistent mumps virus
      infection by vaccination supports the notion that coxsackievirus B and adenovirus
      vaccines may help reduce the incidence of myocarditis.

PMID- 9649941
TI  - The genetics of midline and cardiac laterality defects.
AB  - Left-right asymmetric looping of the cardiac tube during embryogenesis places the
      segments of the cardiac tube that give rise to the left and right chambers into
      their appropriate spatial orientation. Cardiac looping is required for subsequent
      formation of septa, valves, and outflow tract. Defects in embryonic left-right
      axis formation represent a significant portion of congenital heart malformations.
      Recent discoveries make it apparent that the orientation of cardiac tube looping
      is dependent on a cascade of genes in noncardiac embryonic cells, including
      lateral cells and midline cells, before neural tube closure. These observations
      suggest a linkage between complex cardiac defects and subtle midline defects in
      early embryos.

PMID- 9649942
TI  - Mitochondria and heart disease.
AB  - Because the myocardium depends heavily on oxidative metabolism, it is not
      surprising that genetic errors of mitochondrial function often result in
      cardiomyopathies. The emphasis of this review is on disorders of the respiratory
      chain, the only area of cell metabolism that is under dual genetic control: 1)
      the mitochondrial genome (mtDNA) encodes 13 subunits of respiratory chain
      complexes, and 2) the nuclear genome not only encodes all other respiratory chain
      proteins, but also mitochondrial translocases, components of the mitochondrial
      protein transport machinery, and factors that are essential for mtDNA
      transcription, translation, and replication. Mitochondrial cardiomyopathies due
      to mutations in the nuclear DNA are inherited as mendelian traits involving
      structural or enzyme proteins of the respiratory chain, mitochondrial protein
      importation, or the dialogue between the two genomes. Mitochondrial
      cardiomyopathies due to mtDNA mutations can be sporadic or inherited as maternal
      traits and follow the rules of "mitochondrial genetics," which are outlined
      briefly. MtDNA mutations can cause isolated cardiomyopathies or, more often,
      multisystem disorders of which cardiac involvement is a major component. We
      review recent advances in this rapidly expanding field and briefly discuss
      pathogenetic problems and the mitochondrial theory of presbycardia.

PMID- 9649943
TI  - Molecular genetics of Marfan syndrome and Ehlers-Danlos type IV.
AB  - Two inherited disorders of connective tissue have major cardiovascular
      complications, Marfan syndrome and Ehlers-Danlos syndrome type IV. Major progress
      has been made toward understanding both the genetic defect and the molecular
      pathogenesis of these two disorders. Marfan syndrome results from mutations in
      the FBN1 gene, which encodes fibrillin-1, an extracellular matrix component found
      in structures called microfibrils. Histologic characterization of the effect of
      FBN1 mutations on fibrillin-1 cellular processing and microfibril formation has
      provided insights into fibrillin-1 function. Ehlers-Danlos syndrome type IV
      results from mutations in the COL3A1 gene, which encodes the polypeptides in type
      III collagen. Despite advances in the molecular genetics of these two disorders,
      there is not a molecular diagnostic test for these syndromes based on the
      identification of gene mutations. Marfan syndrome remains primarily a clinical
      diagnosis. Biochemical analysis of the amount of type III collagen produced by
      dermal fibroblasts has proven to be a powerful diagnostic test for Ehlers-Danlos
      syndrome type IV.

PMID- 9649944
TI  - Gene therapy and cardiovascular disease.
AB  - This article provides the cardiologist with an overview of recent basic research
      relevant to the application of somatic cell gene therapy against cardiovascular
      disease. Somatic cell gene therapy simply refers to the use of genes as medicine,
      but this is a potent form of medicine that will bring major advances to nearly
      every form of medical practice. In the field of cardiology, research suggests
      that gene therapy may find application against nearly every form of
      cardiovascular disease. Although it is not possible to review every advance in
      the field, this article does provide an overview of some of the gene therapy
      approaches currently being pursued against atherosclerosis, thrombosis,
      restenosis, myocardial infarction, hypertension, heart failure, and transplant
      rejection.

PMID- 9649945
TI  - Genetic aspects of supravalvular aortic stenosis.
AB  - Supravalvular aortic stenosis (SVAS) occurs as an autosomal dominant trait or as
      part of the phenotype of the usually sporadic condition Williams syndrome. SVAS
      is the result of mutation or deletion of the elastin gene (ELN), located at
      chromosome 7q11.23. Thus, SVAS may be more appropriately termed an elastin
      arteriopathy. Studies have demonstrated various point mutations and intragenic
      deletions of ELN resulting in nonsyndromic SVAS. Individuals with Williams
      syndrome are hemizygous for the elastin gene, owing to a 1 to 2 megabase deletion
      of a portion of the long arm of chromosome 7 that encompasses ELN. This
      submicroscopic deletion is readily detected by fluorescent in-situ hybridization,
      useful in the diagnosis of Williams syndrome. The severity of SVAS is quite
      variable, both in series of Williams syndrome patients and within SVAS kindreds,
      suggesting that other genetic factors are involved in expression of the
      phenotype. Experiments with elastin knockout mice will likely yield clues
      regarding the role of elastin in arterial morphogenesis and the pathogenesis of
      obstructive vascular disease.

PMID- 9649947
TI  - Molecular genetics.

PMID- 9649946
TI  - Cardiac failure.

PMID- 9649948
TI  - A simplified diagnostic test for ambulatory screening of peripheral diabetic
      neuropathy.
AB  - The reliability and reproducibility of Michigan Neuropathy Screening Instrument
      (MNSI), a recently proposed simple test for ambulatory screening of peripheral
      diabetic neuropathy (PDN), was evaluated on 80 diabetic patients. MNSI was
      carried out by two diabetologists and repeated after a week. It consisted of the
      sum of scores varying from 0 to 1 for each abnormality revealed in foot
      appearance, achilles reflexes presence and vibratory threshold (VPT) by tuning
      fork (maximum score = 8). Then patients had to go to neurologist for PDN
      diagnosis by a quantitative neurological examination and electrophysiological
      evaluation, the so named Michigan Diabetic Neuropathy Score (MDNS) and the
      results compared with MNSI score according to one of the two observers. The inter
      observer reproducibility of MNSI was 88.75% the within observer reproducibility
      was 95 and 94%, respectively, for each observer with good correlation between the
      two measurements (P < 0.001). The MNSI score of 2.5 as a cut-off appeared to be
      reliable for ambulatory screening of suspected PDN (false positive and false
      negative = 2.5%; specificity and sensitivity = 75% and 78.6%, respectively). In
      conclusion MNSI by using 2.5 score as cut-off may be considered a rapid, simple,
      reproducible and reliable test for rapid ambulatory screening of PDN from the
      diabetologists.

PMID- 9649949
TI  - Islet cell surface antibodies (ICSA) do bind to human pancreas: computerised,
      quantitative determination of ICSA using both pre- and postembedding
      immunocolloidal techniques.
AB  - Islet cell surface antibodies (ICSA) have been demonstrated significantly more
      often in serum of patients with IDDM and their relatives than in healthy
      controls, but some investigators have been unable to show binding to human
      islets. It has therefore been suggested that ICSA is an artefact. We have
      localised and quantified ICSA binding to different specimens, including human
      pancreas. ICSA-positive and ICSA-negative patients' serum, determined by a RIA
      method, were incubated with ultrathin sections of rat insulinoma (RIN5AH) cells,
      stained with Goat-anti-human IgG conjugated with 10 nm gold particles. Sections
      were viewed in transmission electron microscopy (Mag. 30,000 x) and image
      analyses was used to calculate immunolabelling. To test cell specificity we used
      (RIN5AH-cells, rat tumour cells producing growth hormone (GH3), normal human
      pancreas, human insulinoma, and mice liver). Sections showed good morphology.
      ICSA-positive sera, with or without islet cell antibodies (ICA) gave always
      higher immunocolloidal labelling then ICSA-negative sera on RIN5AH sections.
      Thus, the colloidal gold technique could confirm the ICSA results determined with
      RIA. Immunolabelling was pronounced on normal human pancreas and human insulinoma
      cells, but none was found on GH3-cells or mice liver cells. ICSA is not an
      artefact but do exist and bind to human islet cells and therefore maybe can be
      used as a marker for IDDM immunity.

PMID- 9649950
TI  - Changing prevalence of retinopathy in newly diagnosed non-insulin dependent
      diabetes mellitus patients in Hong Kong.
AB  - In this retrospective study, the prevalence of chronic microangiopathic
      complications was determined in 474 Chinese patients with non-insulin dependent
      diabetes mellitus (NIDDM) who presented within 1 year of diagnosis to the
      diabetes clinic from January 1990 to December 1996. Mean age (+/- S.E.) was 53.6
      (+/- 0.6) years. The overall prevalence of retinopathy was 21.9%. A significant
      increase was observed from 1990 to 1994 (P < 0.005), with the prevalence being
      14.8, 13.0, 24.5, 32.3 and 35.4%, respectively, in consecutive years. A
      decreasing prevalence was seen from 1994 to 1996 (P < 0.001), being 8.2 and 7.4%
      in 1995 and 1996, respectively. A total of 95% of patients had nonproliferative
      retinopathy--proliferative retinopathy was found in 5% only. The overall
      prevalence of clinical nephropathy (proteinuria > 0.5 g/day) was 3.7%. Clinical
      neuropathy (increased vibration perception threshold) was found in 12.8% of
      patients. Patients with retinopathy and neuropathy were older (P < 0.0001 and P <
      0.005, respectively) than those without the complications and systolic
      hypertension was more prevalent in patients with retinopathy (P < 0.05). In
      conclusion, a high prevalence of diabetic microangiopathic complications,
      especially of retinopathy, is present in newly diagnosed NIDDM patients in our
      population. It remains to be determined whether the changing prevalence of
      retinopathy at diagnosis bears any relationship to the increasing public
      awareness of diabetes and its complications in Hong Kong in recent years.
      Examination for chronic microangiopathic complications should be carried out in
      all newly diagnosed NIDDM patients.

PMID- 9649951
TI  - Combination insulin and sulfonylurea therapy in insulin-requiring type 2 diabetes
      mellitus.
AB  - PURPOSE: To determine the effect(s) on glucose control, insulin dose, and
      circulating insulin levels of the addition of a sulfonylurea (glipizide) to the
      treatment regimen of patients with insulin-requiring type 2 diabetes mellitus.
      PATIENTS AND METHODS: Thirty seven patients with type 2 diabetes mellitus taking
      insulin for at least 1 year prior to study and treated with > or = 40 U of
      insulin per day were recruited for a randomized, double-blind, placebo
      controlled, crossover trial. Patients were treated with 3 months of insulin +
      placebo (I + P) and 3 months of insulin + glipizide (I + G), with an intermediate
      1 month washout period using insulin therapy alone. Adjustments were made
      initially to the maximum dose of glipizide (40 mg/day), followed by insulin dose
      adjustments. Twenty-nine of the 37 patients demonstrated a significant C-peptide
      response to Ensure and were selected for analysis. RESULTS: The fasting plasma
      glucose in the I + G arm was 6.8 (121.8 mg/dl) vs. 8.7 mmol/L (156.0 mg/dl) in
      the I + P arm, P < 0.001. Mean plasma glucose over 24 hours was 9.8 (176.9 mg/dl)
      for I + G vs. 11.3 mmol/L (203.8 mg/dl) for I + P, P < 0.001. Glycated hemoglobin
      was significantly different (9.8 I + G vs. 11.4% I + P, P < 0.008). The total
      daily insulin dose required was significantly lower with I + G (69.1 vs. 87.3 U,
      P < 0.0005). However, there were no significant differences in free insulin
      levels. CONCLUSION: The addition of a sulfonylurea (glipizide) to insulin therapy
      in patients with insulin-requiring type 2 diabetes mellitus taking large doses of
      insulin results in a rapid and substantial improvement in glucose control despite
      a significant reduction in insulin dose. Therefore, this form of combination
      therapy should be considered for patients with the above characteristics whose
      diet and exercise programs are correct but whose response to insulin therapy is
      inadequate.

PMID- 9649952
TI  - Quantification of apolipoprotein AI-containing lipoprotein particles in non
      insulin-dependent diabetes mellitus.
AB  - Quantification of LpAI (lipoprotein particles containing apolipoprotein AI not
      associated with apolipoprotein AII) was performed through an electroimmunoassay
      on serum from 49 non-insulin-dependent diabetic patients (mean age 60 +/- 9
      years) and 53 age-matched control subjects of both sexes not affected by coronary
      heart disease. Serum lipid and lipoprotein levels were not significantly
      different between the two groups. Serum levels of LpAI determined for diabetic
      patients did not differ from those of control subjects, while concentrations of
      LpAI in men were significantly lower than in women, both among diabetics (P <
      0.05) and controls (P < 0.005). Serum levels of apolipoprotein AI and high
      density lipoprotein cholesterol were significantly correlated with those of LpAI
      (P < 0.005, for both variables). On the contrary, levels of LpAI/AII (lipoprotein
      particles containing both apolipoprotein AI and AII) were significantly increased
      in diabetic patients (P < 0.005).

PMID- 9649953
TI  - Onset age-dependent variations of three islet specific autoantibodies in Japanese
      IDDM patients.
AB  - The age related incidence rate of insulin-dependent diabetes mellitus shows a
      bimodal distribution, not only in Caucasians but also in Japanese. To evaluate
      the onset age-related autoimmune profile at presentation in insulin-dependent
      diabetes mellitus (IDDM), glutamic acid decarboxylase (GAD) autoantibody, islet
      cell antibody (ICA), and insulin autoantibody (IAA) were measured in 137 newly
      diagnosed Japanese IDDM patients with onset ages between 0-29 years. The
      prevalence of GAD autoantibody was significantly increased from the lowest (32%)
      in the 0-5 years onset age group to 75% in the 13-19 years onset age group (P <
      0.05), whereas the IAA prevalence significantly decreased from the peak (48%) in
      the 6-12 years onset age group to 10% in the 20-29 years onset age group (P <
      0.05). The ICA prevalence was increased from the lowest (32%) in the 0-5 years
      onset age group to the highest (53%) in the 20-29 years onset age group similar
      to that for the GAD autoantibody. Such results demonstrate that there was age
      related autoimmune characteristics at presentation of IDDM in Japanese as well as
      in Caucasians.

PMID- 9649954
TI  - Clinical classification of diabetes in tropical west Africa.
AB  - The objective of this work was to classify and describe the different types of
      diabetic patients detected in West Africa. In four health centres (three in Ivory
      Coast, one in Niger) 310 new cases were detected and followed up over 1 year.
      Classification was based on age at diagnosis, BMI, ketonuria, basal and
      stimulated C-peptide levels at inclusion, and response to antidiabetic therapy.
      In this population, males were predominant (sex ratio = 2.40), and random blood
      glucose levels very high at screening (mean +/- SE, 18.6 +/- 0.4 mmol/l). Only
      one case of fibrocalculous pancreatic diabetes and one possible case of diabetes
      mellitus related to malnutrition were detected. IDDM was diagnosed in 11.3% of
      the patients, half of them above 35 years. Leanness was observed in 59% of the
      patients with NIDDM. A dramatic decrease of fasting blood glucose was observed in
      all groups after 2 months of treatment, especially in NIDDM. As IDDM and non
      obese NIDDM presented great similarities before treatment, even for C-peptide
      levels, a point score system is proposed to classify these two groups at
      baseline. In conclusion, it is confirmed that the form of diabetes previously
      defined as related to malnutrition is a very rare entity in black African
      populations. In contrast, African diabetes is characterised by the high
      proportion of NIDDM patients with low BMI, and reduced beta-cell function, rarely
      associated to ketonuria. This form of diabetes seems to be adequately controlled
      with oral hypoglycaemic drugs and/or diet in the year following diagnosis.

PMID- 9649955
TI  - Hypertension and nephropathy in diabetes mellitus: what is inherited and what is
      acquired?
AB  - Prolonged duration of diabetes mellitus, poor long term glycemic control and
      raised blood pressure have all been clearly related to the development of
      diabetic nephropathy. Evidence exists to suggest that a subset of individuals
      with diabetes have a genetic predisposition to diabetic nephropathy. Cases of
      diabetic nephropathy cluster in families and a parental history of hypertension
      is more common in patients with diabetic nephropathy. Current evidence suggests
      an important role for hypertension in the genetic susceptibility to diabetic
      nephropathy but the extent of this is unknown. While cellular and animal studies
      have generated a plethora of data regarding mechanisms involved in the role of
      hypertension and diabetic nephropathy, these are not helpful for drawing
      conclusions in humans. In the following review, we examine the available
      clinical, epidemiologic and family studies to assess the relationship between the
      development of hypertension and diabetic nephropathy in IDDM and NIDDM. We will
      demonstrate the differences in the epidemiology of hypertension in diabetes
      depending on the type of diabetes and thus, move the emphasis of nephropathy
      susceptibility away from hypertension per se. We hope to emphasize instead the
      homogeneity of nephropathy risk in both IDDM and NIDDM and also the idea that a
      common genetic susceptibility exists for all types of diabetes and is conditional
      on cumulative exposure to hyperglycemia. Regarding the interaction of
      hypertension and nephropathy in diabetes mellitus, any conclusions at this time
      about what is inherited and what is acquired must be regarded as speculative.
      However we will discuss some potential mechanisms of hypertension in the
      evolution of nephropathy and we will allude to the role for novel genetic studies
      in the search for nephropathy susceptibility gene(s).

PMID- 9649956
TI  - Salt sensitivity: concept and pathogenesis.
AB  - Almost two decades ago, the existence of a subset of essential hypertensive
      patients, who were sensitive (according to the increase in blood pressure levels)
      to the intake of a diet with a high salt content, was described. These patients
      are characterized by an increase in blood pressure and in body weight when
      switched from a low to a high sodium intake. The increase in body weight is due
      to the incapacity of the kidneys to excrete the whole intake of sodium until
      renal perfusion pressure (mean blood pressure) attains a level that is able to
      restore pressure-natriuresis relationship to values that enable the kidney to
      excrete the salt ingested or administered intravenously. Salt sensitivity does
      not seem to depend on the existence of an intrinsic renal defect to handle
      sodium, but on the existence of subtle abnormalities in the regulation of the
      sympathetic nervous system, the renin-angiotensin system or endothelial function.
      It is also relevant that organ damage secondary to arterial hypertension, has
      been shown in animal models and in hypertensive humans sensitive to a high salt
      intake to be significantly higher when compared with that of salt-resistant
      animals or humans. Interestingly, in humans, salt sensitivity has been shown to
      correlate with microalbuminuria, an important predictor of cardiovascular
      morbidity and mortality, which correlates with most of the cardiovascular risk
      factors commonly associated with arterial hypertension. One of these factors is
      insulin resistance, that usually accompanies high blood pressure in overweight
      and obese hypertensives. Insulin resistance and hyperinsulinism are present in a
      significant percentage of hypertensive patients developing cardiovascular
      symptoms or death. For these reasons, therapy of arterial hypertension must be
      directed, not only to facilitate the lowering of BP level, but also, to halt the
      mechanisms underlying the increase in BP, when salt intake is increased.
      Furthermore, therapy must preferably improve the diminished insulin sensitivity
      present in salt-sensitive subjects that contribute independently to increased
      cardiovascular risk.

PMID- 9649957
TI  - Hypertension and macrovascular disease--the killing fields of NIDDM.
AB  - Diabetes mellitus and particularly non-insulin-dependent diabetes mellitus
      (NIDDM) increases the risk for all manifestations of: (a) atherosclerotic
      vascular disease; (b) coronary heart disease (CHD); (c) cerebrovascular disease;
      and (d) peripheral vascular disease. NIDDM is known to be associated with several
      adverse cardiovascular risk factors, including: (i) hypertension; (ii) obesity;
      (iii) central obesity; (iv) hyperinsulinemia; and (v) serum lipid and lipoprotein
      abnormalities, characterized mainly by elevated serum total triglycerides and low
      high-density lipoprotein cholesterol. This review will discuss the prevalence of
      hypertension in NIDDM, the role of hypertension to increase the risk for
      macrovascular complications in NIDDM and finally trial evidence for the
      beneficial effect of blood pressure lowering in patients with NIDDM.

PMID- 9649958
TI  - Progression of diabetic nephropathy. A focus on arterial pressure level and
      methods of reduction.
AB  - It is well accepted that a reduction of arterial pressure to levels of less than
      140/90 mmHg will slow the decline in renal function among patients with diabetic
      nephropathy. More recently it is appreciated that the reduction of arterial
      pressure to levels much below 130/85 mmHg provides even greater levels of
      protection against the progression of renal disease. Given that the achievement
      of blood pressure reduction to such a level requires more than one medication and
      that the patient's compliance is best with a once-daily medication, it makes
      sense to combine antihypertensive medications so as to maximize the benefit. In
      this way, fixed dose combination medications yield synergistic effects on blood
      pressure reduction while providing, in some cases, maximal benefit to
      preservation of renal function. Such a combination is the verapamil/trandolapril
      combination. This paper discusses in great detail the advantages of blood
      pressure reduction and the types of medications that may achieve both protection
      against diabetic nephropathy progression as well as blood pressure reduction.

PMID- 9649959
TI  - Is antihypertensive treatment the same for NIDDM and IDDM patients?
AB  - The prevalence of abnormally elevated albumin excretion rate (> 30 mg/24 h) is
      approximately 40% in insulin-dependent (IDDM) and non-insulin-dependent (NIDDM)
      diabetic patients. Diabetes has become the leading cause of end-stage renal
      failure in the US, Japan and Europe. Approximately 90% of the direct and indirect
      cost of caring for diabetic patients are spent on the complications of diabetes.
      Identification of patients at high risk of developing diabetic nephropathy is
      possible by screening for microalbuminuria (30-300 mg/24 h). Elevated urinary
      albumin excretion rate indicates a substantially increased mortality risk in
      diabetic patients. Randomised controlled trials in normotensive IDDM and NIDDM
      patients with persistent microalbuminuria indicate that ACE inhibitors diminish
      urinary albumin excretion rate, postpone it and may even prevent progression to
      clinical overt nephropathy. These findings indicate that screening and
      intervention programs are likely to have life saving effects and lead to
      considerable economic savings. Systemic blood pressure elevation to a
      hypertensive level is an early and frequent phenomenon in diabetic nephropathy.
      Furthermore, nocturnal blood pressure elevation (non-dippers) occurs more
      frequently in patients with nephropathy. Systemic blood pressure elevation and to
      a lesser degree albuminuria accelerate the progression of diabetic nephropathy.
      Effective blood pressure reduction with non-ACE-inhibitors and/or ACE-inhibitors
      frequently in combination with diuretics: (a) reduces albuminuria; (b) delays the
      progression of nephropathy; (c) postpones renal insufficiency; and (d) improves
      survival in IDDM and NIDDM patients with diabetic nephropathy. A specific renal
      protective effect of ACE-inhibitors in diabetic nephropathy has been demonstrated
      in IDDM patients with moderately reduced kidney function (s-creatinine > 133
      mumol/l) while the data conflict with NIDDM patients. Antihypertensive treatment
      for diabetic nephropathy simultaneously extends life and saves money. Finally,
      reduced risk of fatal and non-fatal cardiovascular events have been demonstrated
      when diabetic patients with isolated systolic hypertension are treated with blood
      pressure lowering agents. Absolute risk reduction with active treatment compared
      to placebo was twice as great for the diabetic versus non-diabetic patients
      (101/1000 versus 51/1000 randomised participants at the 5-year follow-up),
      reflecting the higher risk of diabetic patients. In conclusion, early detection
      and aggressive treatment of arterial hypertension with ACE-inhibitors, long
      acting calcium antagonist and low dose diuretics as first line drugs are highly
      warranted in diabetic patients with or without diabetic renal disease.

PMID- 9649960
TI  - Prognosis of diabetic nephropathy: how to improve the outcome.
AB  - Chronic renal diseases, including diabetic nephropathy, evolve to terminal renal
      failure by a process leading to progressive parenchimal damage which appears
      relatively independent of the initial insult. When glomerular permselectivity is
      lost, proteins filtered through the glomerular capillary, through proximal
      tubular cell activation and up-regulation of genes of inflammatory and vasoactive
      mediators, may give rise to an inflammatory reaction that in the long-term can
      contribute to renal scarring. If this interpretation is correct, the best
      approach to try to retard the progression of several renal diseases would be to
      limit the excessive traffic of macromolecules throughout the glomerular capillary
      by molecules, as the angiotensin-converting-enzyme (ACE) inhibitors, that may
      help restore perm-selective properties to normal. Thus, the present review
      addresses the mechanism(s) of the renal protective effect of ACE inhibitors and
      analyzes the evidence so far available of their salutary effect in human
      nephropathies, with particular focus on diabetic nephropathy. The issue of
      whether ACE inhibitors alone or in combination with other antihypertensives
      (namely non-dihydropyridinic calcium channel blockers) may even prevent the onset
      of nephropathy at the stage of normoalbuminuria is discussed.

PMID- 9649961
TI  - Investigation of hallucinogenic and related beta-carbolines.
AB  - Certain beta-carbolines are known to be hallucinogenic in humans, and several
      produce stimulus effects in animals similar to those of the classical
      hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM). Classical
      hallucinogens bind at 5-HT2 serotonin receptors and these receptors are thought
      to play a role in their mechanism of action. In the present study, we examined
      the binding of 15 beta-carbolines at rat 5-HT2A and 5-HT2C receptors. Affinities
      (Ki values) of the beta-carbolines ranged from about 100 nM to greater than
      10,000 nM depending upon the degree of saturation of the pyridyl ring, and upon
      the presence and location of methoxy substituents in the benzenoid ring. In a
      further study, six rats were trained to discriminate the hallucinogenic beta
      carboline harmaline (3.0 mg/kg, i.p.) from vehicle using a VI-15s schedule of
      reinforcement. This represents the first time a hallucinogenic beta-carboline has
      been used as a training drug in a drug discrimination study. Administration of
      DOM to the harmaline-trained animals resulted in 76% harmaline-appropriate
      responding at 1.25 mg/kg DOM and disruption of behavior at a higher dose. Taken
      together, the results of the present investigation demonstrate that: (a) certain
      beta-carbolines bind at 5-HT2 receptors; (b) that harmaline serves as a training
      drug at 3.0 mg/kg in drug discrimination studies with rats as subjects; and that
      (c) there is some similarity between the stimulus effects produced by harmaline
      and DOM.

PMID- 9649962
TI  - Predictors of cessation of marijuana use: an event history analysis.
AB  - Event history analysis was applied to monthly life and drug histories of a
      representative community sample of 706 marijuana users, followed from ages 15-16
      to 34-35, to investigate factors associated with cessation of marijuana use from
      adolescence to adulthood. In addition to age and gender, the most important
      determinants of cessation are the phenomenology of marijuana use, social role
      participation, depressive symptoms and deviance. Frequent users, those who
      started using early and those who use illicit drugs other than marijuana are more
      likely to continue their marijuana use. Using marijuana for social reasons
      accelerates cessation, using to change one's mood reduces cessation. Becoming
      pregnant and a parent is the most important social role leading to marijuana
      cessation for women. There is also a very important experimental effect of the
      interview itself on the reported timing of a cessation. The effect of a social
      context favorable to marijuana use appears to reflect selection rather than
      social influence.

PMID- 9649963
TI  - Separation of the locomotor stimulant and discriminative stimulus effects of
      cocaine by its C-2 phenyl ester analog, RTI-15.
AB  - During a routine evaluation of several analogs of cocaine, we observed that the C
      2 phenyl ester, RTI-15, appeared to suppress motor activity in rats. We
      subsequently examined RTI-15 for its cocaine-like stimulus effects as well as for
      its locomotor activity effects. RTI-15 dose-dependently generalized from the
      cocaine stimulus in rats trained to discriminate 10 mg/kg cocaine from saline
      with complete substitution (> or = 80% cocaine-lever responding) occurring at 24
      mg/kg. During automated locomotor activity tests in mice, cocaine (3-60 mg/kg)
      dose-dependently increased activity counts and movement time across the entire 1
      h test session. RTI-15, however, had little affect on activity counts and
      movement time from 10-30 mg/kg, and decreased these measures at 60 mg/kg, the
      highest dose tested. These results indicate that while changing the C-2 methyl
      ester of cocaine to a C-2 phenyl ester increases dopamine-transporter
      selectivity, it dissociates its locomotor activity effects from its
      discriminative stimulus effects suggesting that the underlying mechanisms
      mediating these effects are not identical.

PMID- 9649964
TI  - A comparison of subjective, psychomotor and physiological effects of a novel
      muscarinic analgesic, LY297802 tartrate, and oral morphine in occasional drug
      users.
AB  - This study compared the subjective, physiological and psychomotor effects of a
      novel muscarinic analgesic (LY297802) and oral morphine in healthy volunteers.
      Nine, non-dependent, occasional drug users participated in nine experimental
      sessions in which they received the following conditions: placebo, 0.1, 0.3, 0.56
      and 1 mg of oral LY297802 and 10, 30, 56 and 100 mg of oral morphine. Subjective
      drug effects were assessed using the Visual Analog Scale (VAS), the Addiction
      Research Center Inventory (ARCI) and subjective and objective agonist and
      antagonist scales of the Adjective Rating Scale (ARS). These measures were
      collected 30 min before and every 30 min post drug administration for a 4-h
      period. Psychomotor performance was evaluated using the Digit Symbol Substitution
      Test (DSST) at these same time intervals. Physiological measures were collected
      continuously throughout the sessions. Oral morphine produced significant
      increases in some subjective effects scales, including elevations on the VAS,
      ARCI and ARS. In contrast, LY297802 did not engender changes different from
      placebo on any of these indices. Morphine produced significant dose-dependent
      effects in DSST performance, heart rate, blood oxygen saturation and pupil
      diameter. LY297802 significantly and dose dependently increased heart rate, mean
      arterial pressure and diastolic blood pressure. These results suggest that
      LY297802 does not induce subjective effects similar to morphine, but that it has
      some significant physiological effects.

PMID- 9649965
TI  - Impulsivity and history of drug dependence.
AB  - Impulsivity was contrasted between 32 subjects with a history of drug-dependence
      (DRUG+) and 26 subjects with no drug use history (DRUG-) using both behavioral
      and self-report measures. The hypothesis was that the DRUG+ group would be more
      impulsive than the DRUG- group. Subjects in the DRUG+ group self-reported more of
      a tendency toward impulsivity than the DRUG- group in the situations posed in
      questionnaires. In the behavioural paradigm involving a choice between a smaller
      intermediate reward and a larger but delayed reward, DRUG+ subjects selected the
      impulsive option more often, but these differences were not significant. The
      DRUG+ and DRUG- groups did differ on the mean delay interval for the larger
      reward, indicating less ability to tolerate longer delays for the larger reward.
      A frequency distribution of delay intervals for the larger reward indicated that
      DRUG+ subjects were more likely to maintain very short intervals and less likely
      to maintain longer intervals.

PMID- 9649966
TI  - Effects of chronic opioid dependence and HIV-1 infection on pattern shift visual
      evoked potentials.
AB  - The goal of the present study was to examine the effects of opioid dependence,
      alone and in combination with asymptomatic HIV-1 infection, on the pattern shift
      visual evoked potential (PSVEP). For this purpose, three groups of patients were
      evaluated, including patients characterized by: (1) a past history (2-4 months
      abstinent) of DSM-IIIR opioid dependence (i.e. in partial remission); (2) a
      recent history (7 days abstinent) of opioid dependence with ongoing methadone
      maintenance; and (3) a recent history of opioid dependence, ongoing methadone
      maintenance, and asymptomatic HIV-1 infection. A group of healthy, non-drug
      dependent volunteers was also evaluated. Analyses revealed no PSVEP differences
      between patients with a past history of opioid dependence and healthy volunteers.
      There were also no PSVEP differences between methadone-maintained patients with
      or without HIV-1 infection. Collectively, however, the two methadone maintenance
      groups exhibited significant delays in the N75 and P100 components of the PSVEP
      relative to the other two groups. The delay in N75 latency was strongly
      correlated with self-reported years of heroin abuse, but not with years of
      cocaine, alcohol, or other drug abuse. These results are interpreted as
      reflecting an adverse effect of chronic opioid dependence on neural transmission
      within primary visual areas of the brain.

PMID- 9649967
TI  - Effects of nicotine on methadone self-administration in humans.
AB  - The effects of nicotine abstinence, ad libitum smoking, and 0, 2, and 4 mg
      nicotine gum on methadone self-administration were investigated. Five methadone
      maintained patients with a history of smoking (18-30 cigarettes/day) were
      recruited as subjects. Upon arrival expired carbon monoxide levels were measured
      to confirm self-reported abstinence of 10-12 h. At 30 min prior to the methadone
      self-administration session, two response options were concurrently available.
      When a 64-button press requirement (FR64) was completed, 10 ml of 0.054 mg/ml
      methadone solution, or vehicle, was delivered. Immediately following, and 30, 60,
      90, and 120 min after the self-administration session, expired carbon monoxide
      levels and typical symptoms of nicotine withdrawal were assessed. Relative to
      abstinence, subjects consumed more methadone following the 4-mg nicotine gum and
      ad libitum smoking conditions. Ratings of cigarette craving were significantly
      less following ad libitum smoking or administration of 4-mg nicotine gum, than
      following abstinence. Implications for understanding opioid and nicotine
      interactions are discussed.

PMID- 9649968
TI  - Using geographic information systems to assess spatial patterns of drug use,
      selection bias and attrition among a sample of injection drug users.
AB  - This study sought to assess whether frequency and type of drug use are
      geographically located within the city of Baltimore independent of neighborhood
      characteristics. The second goal was to assess geographic factors associated with
      sample selection and attrition. The sample consisted of 597 inner-city injection
      drug users who were enrolled in a HIV prevention study. The residential locations
      were plotted using Geographic Information Systems (GIS) software. Three patterns
      of drug use in the prior 6 months were examined: daily use of injection heroin,
      daily use of injection cocaine and any use of crack cocaine. Daily use of cocaine
      and any use of crack were found to be statistically associated with residing in
      the western portion of the city and distance from the western district sexually
      transmitted disease clinic. After adjusting for individual level characteristics
      and neighborhood level variables, as measured by 1990 census tract data, daily
      use of cocaine was found to be associated with residing in a more southern area
      of the city and distance from the western district sexually transmitted disease
      clinic, and any crack use was found to be associated with residing in a more
      western area of the city and distance from the western district sexually
      transmitted disease clinic. Men and younger participants were more likely to
      reside further away from the study clinic as were individuals who dropped out of
      the intervention condition. The results of this study suggest that type and
      frequency of drug use is associated with specific geographic areas, independent
      of neighborhood characteristics. These results have implications for the location
      of drug prevention, needle exchange and other HIV prevention activities.

PMID- 9649969
TI  - Computers in community-based drug and alcohol clinical settings: are they
      acceptable to respondents?
AB  - The use of computer technology is not new in the delivery of health services.
      Previous studies have assessed the reliability and validity of computerised
      surveys, relative to pen and paper versions or interviews or the acceptability of
      computers in a range of treatment settings. Generally, these studies have
      reported that the reliability, validity and acceptability of computer surveys is
      at least comparable to more traditional survey methods. This study provides
      evidence for the appropriateness of using computers in community-based drug and
      alcohol clinical settings, reporting a high level of computer acceptability among
      clients. The advantages of utilising computers in clinical settings, for
      researchers and clinicians, are discussed.

PMID- 9649970
TI  - Attention and memory in illicit amphetamine users: comparison with non-drug-using
      controls.
AB  - The purpose of this study was to clarify the extent of neuropsychological
      impairment previously found among amphetamine users (McKetin and Mattick, 1997)
      by comparing them with a non-drug-using control group. Amphetamine users who were
      classified as low dependence (n = 15) or high dependence (n = 11) according to
      the severity of dependence scale (SDS) were compared to non-drug-using control
      subjects (n = 9) on indices of the Wechsler Memory Scale-Revised (WMS-R).
      Dependent amphetamine users (high dependence group) performed approximately one
      half of a standard deviation worse than controls on the verbal memory,
      attention/concentration and delayed recall indices of the WMS-R but amphetamine
      users who were less dependent (low dependence group) showed no impairment.

PMID- 9649971
TI  - Regional cerebral blood flow during acute and chronic abstinence from combined
      cocaine-alcohol abuse.
AB  - Regional cerebral blood flow (rCBF) was assessed using SPECT and HMPAO in ten
      cocaine abusers within 72 h of last cocaine use and then after 21 days of
      abstinence. In comparison to normals the cocaine abusers had significantly
      reduced rCBF in 11 of 14 brain regions with the largest reductions in the frontal
      and parietal cortex and greater rCBF in the brain stem. These perfusion defects
      appeared to be primarily due to combined alcohol and cocaine abuse and frontal
      but not parietal defects appeared to resolve partially during 21 days of
      abstinence.

PMID- 9649972
TI  - A mathematical model of HIV transmission in NSW prisons.
AB  - A mathematical model was developed to estimate HIV incidence in NSW prisons. Data
      included: duration of imprisonment; number of inmates using each needle; lower
      and higher number of shared injections per IDU per week; proportion of IDUs using
      bleach; efficacy of bleach; HIV prevalence and probability of infection. HIV
      prevalence in IDUs in prison was estimated to have risen from 0.8 to 6.7% (12.2%)
      over 180 weeks when using lower (and higher) values for frequency of shared
      injections. The estimated minimum (and maximum) number of IDU inmates, infected
      with HIV in NSW prisons was 38 (and 152) in 1993 according to the model. These
      figures require confirmation by seroincidence studies.

PMID- 9649973
TI  - Prenatal cocaine exposure and school-age intelligence.
AB  - Assessments of the possible consequences of prenatal exposure to cocaine have
      been limited by lack of control for socio-demographic confounders and lack of
      follow-up into the school years. We evaluated intelligence at ages 6-9 years in
      88 children from a cohort of 280 born between September 1, 1985 and August 31,
      1986 and identified at birth as cocaine-exposed, and in a group of unexposed (n =
      96) births of comparable gender and birthweight. IQ scores did not differ between
      children with and without prenatal exposure to cocaine (mean 82.9 vs. 82.4,
      difference = 0.5 points, 95% CI-3.1, 4.1); results were unchanged with adjustment
      for child height, head circumference and prior residence in a shelter or on the
      street, and for caregiver IQ and home environment (mean difference = 2.2 points,
      95% CI-1.5, 5.8).

PMID- 9649974
TI  - The differential effects of alcohol consumption and dependence on adverse alcohol
      related consequences: implications for the workforce.
AB  - Previous literature has supported the hypothesis that high rates of alcohol
      consumption are associated with adverse social consequences and that dependence
      on alcohol has an effect on that relationship. The purpose of this paper is to
      further specify the alcohol consumption-adverse consequences linkage by
      developing and estimating a latent variable model that incorporates the mediating
      effects of loss of control over alcohol consumption. This model is applied to
      measures for three alcohol-related constructs--consumption, loss of control and
      adverse consequences--incorporated in the 1991 National Household Survey on Drug
      Abuse, for members of the primary workforce in the US. The research suggests that
      workplace decision makers attempting to minimize the adverse workplace
      consequences of alcohol abuse should implement procedures that assess and respond
      to alcohol dependency rather than relying exclusively on detection of and
      intervention with alcohol consumption per se.

PMID- 9649975
TI  - Fluoxetine treatment of depressive disorders in methadone-maintained opioid
      addicts.
AB  - This study tested the effectiveness of fluoxetine as a treatment for depression
      in a population of methadone-maintained opioid addicts. Methadone-maintained
      opioid addicts (44) with depression received fluoxetine or placebo in addition to
      their methadone, in a double-blind randomized trial, for 12 weeks. Depressive
      symptoms decreased significantly overall with no significant differences between
      the groups treated with fluoxetine versus placebo. In addition, drug use
      outcomes, including cocaine and heroin self-reported use and urine toxicology
      were measured. There was a significant decrease in heroin use in treatment, but
      no medication effect. Cocaine use, was unchanged from pre-treatment to endpoint.
      In separately analyzing data for the subsample of subjects with the most severe
      depression, there was a significant decrease in depression during treatment and a
      significant decrease in self-reported cocaine use, but no medication effect on
      either depressive symptoms or on cocaine use. This study suggests that fluoxetine
      is not an effective agent in treating depression or cocaine use in this
      population.

PMID- 9649976
TI  - Accelerated lofexidine treatment regimen compared with conventional lofexidine
      and methadone treatment for in-patient opiate detoxification.
AB  - This open study compares an accelerated 5-day lofexidine regimen with orthodox 10
      day lofexidine and methadone regimens in the treatment of opiate withdrawal in 61
      polysubstance abusing opiate addicts. Significant differences in levels of
      withdrawal symptoms were found on days 11, 13-15 and 17-20, symptoms resolving
      most rapidly in the 5-day lofexidine treatment group, whilst withdrawal responses
      in the 10-day lofexidine treatment group were intermediate between the 5-day
      lofexidine and standard methadone treatment conditions. When the two lofexidine
      regimens were separately compared with methadone the 5-day lofexidine treatment
      was significantly more effective on day 10, 11 and 13-20, whilst the 10-day
      lofexidine treatment was not significantly different from methadone. There were
      no significant differences in rates of completion of detoxification between the
      three treatments. Both the lofexidine treatment regimens had a similar effect on
      blood pressure. Five patients experienced side effects which resolved with dose
      reduction, all remaining in the study. An accelerated 5-day lofexidine regimen
      may attenuate opiate withdrawal symptoms more rapidly than conventional 10-day
      lofexidine or methadone treatment schedules without exacerbating hypotensive side
      effects.

PMID- 9649977
TI  - Treatment failure and methadone dose in a public methadone maintenance treatment
      programme in Geneva.
AB  - The aim of this study was to identify predictors of treatment failure in a
      methadone maintenance treatment programme in Geneva. All patients (n = 149)
      starting treatment between May 1993 and May 1995 were followed until end of
      treatment or 31st July 1996. The proportion of depressed patients decreased
      significantly over time, as did the proportion of those injecting illegal drugs.
      The overall treatment failure was 21%. The probability of treatment failure was
      higher for women than for men (RR 2.2, P = 0.03) and decreased in successive
      cohorts. There was no correlation between the methadone dose at 2 months and
      treatment outcome, probably because doses were individualised and the associated
      level of psycho-social services high.

PMID- 9649978
TI  - Autoradiographic analysis of cannabinoid receptor binding and cannabinoid agonist
      stimulated [35S]GTP gamma S binding in morphine-dependent mice.
AB  - The present study was designed to test the possible existence of changes in brain
      cannabinoid receptors in morphine-dependent mice. To this end, we compared
      cannabinoid receptor binding and WIN 55,212-2-stimulated [35S]guanylyl-5'-O
      (gamma-thio)-triphosphate ([35S]GTP gamma S) binding in several brain regions of
      mice chronically exposed to morphine or saline. The existence of opiate
      dependence in morphine-injected mice was assessed by analyzing the well-known
      jumping behavior induced by the blockade of opioid receptors with naloxone,
      whereas these animals were unresponsive to the blockade of cannabinoid receptors
      with SR141716. The different structures analyzed exhibited similar cannabinoid
      receptor binding levels in morphine-dependent and control mice, with the only
      exception of the globus pallidus, which exhibited a very small, but statistically
      significant, increase. In addition, the activation of cannabinoid receptors with
      WIN 55,212-2 increased [35S]GTP gamma S binding in most of the structures
      examined. The increase was of similar magnitude in morphine-dependent and control
      mice, except in the substantia nigra, where morphine-dependent mice exhibited
      lesser [35S]GTP gamma S binding levels in basal conditions, although a
      significantly higher WIN 55,212-2-stimulated binding. Other structures, such as
      the central gray substance, where there was a poor agonist-induced stimulation in
      control mice, exhibited, however, higher levels of WIN 55,212-2-stimulated
      [35S]GTP gamma S binding in morphine-dependent mice, whereas these animals tended
      to exhibit a higher [35S]GTP gamma S binding levels in basal conditions, although
      a lesser and not statistically significant WIN 55,22-2-stimulated binding, in the
      deep layers of the cerebral cortex. Thus, the data support the potential
      existence of a specific effect of morphine in the coupling of cannabinoid
      receptors to GTP-binding proteins, rather than on receptor binding, although this
      was observed only in the substantia nigra and central gray substance.

PMID- 9649979
TI  - Randomised double-blind comparison of lofexidine and clonidine in the out-patient
      treatment of opiate withdrawal.
AB  - This study compares the clinical response to lofexidine and clonidine in the out
      patient treatment of opiate withdrawal in 50 opiate addicts, using a randomised
      double-blind study design. Patients were taking 40 mg or less methadone daily, or
      equivalent amounts of other opiates. Fifty-eight percent of those starting
      treatment completed detoxification, and were opiate free at 4 weeks: more
      patients completed withdrawal in the lofexidine group, but the difference was not
      significant. Clonidine produced more hypotensive effects: more home visits were
      also required by medical staff. There was no other significant difference in side
      effects. Both drugs can be used successfully in out-patient detoxification, but
      lofexidine is more economical in regard to staff time.

PMID- 9649980
TI  - Acute pain services: transition from the Middle Ages to the 21st century.

PMID- 9649981
TI  - Who was the first to monitor blood pressure during anaesthesia?

PMID- 9649982
TI  - Local vs. systemic immune and haemostatic response to hip arthroplasty.
AB  - Local and systemic immune and haemostatic responses were studied in 10 patients,
      aged 57-78 years, undergoing elective hip arthroplasty. Cytokines, soluble
      cytokine receptors, interleukin-1 receptor antagonist, soluble adhesion
      molecules, antithrombin, fibrin, soluble and fibrin D-dimer were analysed in
      wound drainage blood and in blood taken from the systemic circulation for up to
      24 h post-operatively. Wound drainage blood concentrations of cytokines,
      interleukin-1 receptor antagonist and soluble cytokine receptors were increased
      compared with those in the systemic circulation except for the soluble
      interleukin-6 receptor. In wound drainage blood, soluble tumour necrosis factor
      receptors (P < 0.05), interleukin-1 receptor antagonist (P < 0.05) and
      interleukin-6 (P < 0.05-< 0.01) increased during the study period. In blood from
      the systemic circulation interleukin-6 increased (P < 0.05) while the soluble
      interleukin-6 receptor decreased (P < 0.05) compared with pre-operative values.
      Concentrations of soluble adhesion molecules did not change. Wound drainage blood
      showed marked hypercoagulation. After hip arthroplasty pro-inflammatory cytokines
      and their inhibitors were mainly confined to the local trauma site. A
      predominance for inhibitors was noted.

PMID- 9649983
TI  - An audit of post-operative pain and nausea in day case surgery.
AB  - A telephone audit was carried out on patients 24 hours after day case surgery. An
      initial audit shortly after the day case opened indicated pain scores and nausea
      that were considered unacceptable. Some 8.6% of patients called their family
      doctor (GP) to visit their home in the post-operative period. Pre-operative
      Piroxicam 20 mg was then initiated (in most patients) to reduce the pain scores,
      which it did. Only one patient in 111 (0.9%) called their GP out, but nausea
      scores remained unchanged. Methods to reduce this index are suggested.

PMID- 9649984
TI  - Effect of diluent volume on post-operative analgesia and sedation produced by
      epidurally administered midazolam.
AB  - We have studied the optimal diluent volume for post-operative analgesia and
      sedation produced by epidurally administered midazolam after upper abdominal
      surgery. Sixty patients were randomly allocated to four groups of 15 patients.
      When patients complained of pain after surgery, epidural midazolam 0.05 mg kg-1
      in 3 mL saline (Group A), in 5 mL saline (Group B), in 10 mL saline (Group C) or
      in 15 mL saline (Group D) were injected as a bolus. The sedation was better and
      lasted longer in groups B and C than in the other two groups. Groups B and C also
      had significantly more extensive areas of analgesia than groups A and D from 30
      min after the administration of midazolam. The interval to the second request for
      an analgesic was significantly shorter in Group D than in the other three groups.
      Memory retention of the pin-prick examination was reported by four patients in
      Group A. The present results indicate that 5-10 mL saline is the optimal volume
      for epidural injection when using midazolam 0.05 mg kg-1 for post-operative
      analgesia following upper abdominal surgery.

PMID- 9649985
TI  - Sevoflurane anaesthesia in paediatric patients: better than halothane?
AB  - Forty-two children (aged 2-16 years) were randomly assigned to receive either
      sevoflurane (n = 21) or halothane (n = 21) in nitrous oxide/oxygen. After pre
      medication with midazolam, anaesthesia was induced by facemask and the
      anaesthetic concentration was increased until loss of eyelash reflex
      (sevoflurane, 6%; halothane, 2.5%). Thereafter, 1-1.5 MAC of the inhalational
      agents were maintained until skin closure. Intra-operative analgesia was provided
      either by intermittent intravenous (i.v.) bolus doses of fentanyl (2-3 micrograms
      kg-1) or by a regional blockade. Induction was smooth and the time to loss of
      eyelash reflex was slightly shorter with sevoflurane than with halothane, the
      difference not quite reaching statistical significance (P = 0.06). In both
      groups, heart rate remained stable and blood pressure decreased significantly
      during induction. Haemodynamic parameters remained stable during anaesthetic
      maintenance; no cardiac dysrhythmias were observed. Emergence time with
      sevoflurane was 12.9 min vs. 16.3 min with halothane, but this difference was not
      statistically significant. It is concluded that sevoflurane is as suitable for
      paediatric patients as halothane. The slightly faster emergence time offered by
      sevoflurane over halothane was of no clinical significance in the present study.

PMID- 9649987
TI  - Clonidine prolongs fentanyl-induced ventilatory depression.
AB  - The aim of the present study was to investigate the effect of intravenously
      (i.v.) administered fentanyl and clonidine on ventilation in 12 healthy male
      volunteers (age 30.8 +/- 4.9 years) who either received fentanyl alone (1.5 > or
      = micrograms kg-1) or fentanyl (1.5 > or = micrograms kg-1) in combination with
      clonidine (3 > or = micrograms kg-1). The effect on ventilation was measured with
      a CO2 rebreathing system. The respiratory depression caused by fentanyl
      disappeared 120 min after injection. The corresponding slopes were 7430 +/- 2075
      mL kPa-1 prior to (t0) and 6263 +/- 1864 mL kPa-1 120 min post-application (base
      line vs. t120; P = 0.106). An impaired ventilatory response was observed during
      CO2 rebreathing at t120 after the injection of fentanyl and clonidine. Before
      drug administration, the slope of the response curves was 7700 +/- 2800 mL kPa-1,
      which was reduced to 5480 +/- 2135 mL kPa-1 (P < 0.035) at t120. These data
      suggest a prolongation of a fentanyl-induced ventilatory depression when used in
      combination with clonidine.

PMID- 9649986
TI  - Effective dose of granisetron for the prevention of post-operative nausea and
      vomiting in patients undergoing laparoscopic cholecystectomy.
AB  - This study was undertaken to determine the minimum effective dose of granisetron,
      a selective 5-hydroxytryptamine type 3 receptor antagonist, for the prevention of
      post-operative nausea and vomiting (PONV) in female patients undergoing elective
      laparoscopic cholecystectomy. In randomized, placebo-controlled, double-blind
      study, 120 women were assigned to receive either placebo (saline) or granisetron
      at three different doses (20 micrograms kg-1, 40 micrograms kg-1 or 80 micrograms
      kg-1) intravenously immediately before the induction of anaesthesia. All patients
      received standardized anaesthesia consisting of isoflurane and nitrous oxide in
      oxygen. The incidence of PONV during the first 24 hours after anaesthesia was 43,
      40, 13 and 13% after administration of placebo and granisetron 20 micrograms kg
      1, 40 micrograms kg-1 and 80 micrograms kg-1, respectively (P < 0.05, overall
      Fisher's exact probability test). Adverse effects post-operatively were not
      different among the groups. In conclusion, granisetron 40 micrograms kg-1 is the
      minimum effective dose in the prevention of PONV after laparoscopic
      cholecystectomy.

PMID- 9649988
TI  - Pharmaco-economic evaluation of a disposable patient-controlled analgesia device
      and intramuscular analgesia in surgical patients.
AB  - The present study contrasted the pharmaco-economics and analgesic efficacy of
      intramuscular (i.m.) opioid treatment with a parenteral disposable patient
      controlled analgesia (PCA) system in two groups of 20 female patients (ASA I-II,
      aged 35-69 years) scheduled for abdominal hysterectomy. The PCA group received a
      continuous infusion of 1.5 mg h-1 piritramide, a mu-opioid receptor agonist, with
      incremental doses of 1.5 mg (lock-out interval = 15 min). The i.m. group received
      0.3 mg kg-1 piritramide i.m. when requested by the patient with a minimum
      interval of 5 h. Pain intensity, sedation and the functional recovery of the
      patients were followed for 72 h post-operatively. The sum of pain intensity
      differences (SPID) was used as a measure of analgesic efficiency. Equipment and
      drug costs, and the demand on nursing time were recorded over 3 days post
      operatively. The costs of PCA and i.m. therapies per patient were used to
      calculate the cost-benefit (cost of treatment vs. nursing time) and cost
      effectiveness (cost of treatment vs. SPID) analyses. Both treatments initially
      provided comparable analgesia, but PCA was more efficient after 16 h and
      significantly reduced nursing time for pain treatment (PCA = 61 +/- 4 min, i.m. =
      88 +/- 5 min; P < 0.001). Functional recovery was not different for either
      treatment. Cost analysis indicated a better cost-benefit ratio for the i.m.
      treatment (0.35 vs. 1.1 for PCA treatment), but a similar cost-effectiveness for
      both treatments (PCA = 1.9 Belgian Francs (BEF) unit-1 SPID; i.m. = 1.7 BEF unit
      1 SPID).

PMID- 9649989
TI  - Addition of droperidol to morphine administered by the patient-controlled
      analgesia method: what is the optimal dose?
AB  - Eighty patients were recruited into a double-blind, randomized trial to find the
      optimal dose of droperidol for addition to the patient-controlled analgesia (PCA)
      morphine infusate for female patients undergoing gynaecological surgery. A
      standardized anaesthetic technique was employed. Post-operative analgesia was
      provided by PCA morphine. Patients were allocated at random into one of four
      treatment groups receiving with each PCA morphine bolus: (1) droperidol 0.05 mg;
      (2) droperidol 0.10 mg; (3) droperidol 0.15 mg; and (4) droperidol 0.20 mg,
      respectively. The incidence of post-operative nausea and vomiting (PONV),
      requests for rescue anti-emetic medication, and incidence of side effects were
      recorded. The number of symptom-free patients in each group increased as the
      droperidol dose increased, but although there was a significant inverse
      association between the total dose of droperidol received and the severity of
      PONV (P < 0.05), there were no significant differences between individual groups.
      In each group, patients were significantly less sedated at 24 h compared with 12
      h (P < 0.01). However, after 24 h, patients in group 4 were significantly more
      sedated than patients in groups 1 and 2 (P < 0.05). There were no significant
      differences between the groups in terms of the incidence of anxiety or other side
      effects attributable to droperidol. The present authors suggest that, although
      the results demonstrate few statistically significant differences between the
      four groups, a PCA bolus dose of droperidol of 0.10 mg mL-1 appears to provide
      the optimal balance between anti-emetic efficacy and an acceptable incidence of
      side effects.

PMID- 9649990
TI  - Comparison of time course of neuromuscular blockade in young children following
      rocuronium and atracurium.
AB  - In order to compare the neuromuscular effects following rocuronium 0.6 mg kg-1
      and atracurium 0.5 mg kg-1 30 children aged from 18 to 67 months were studied
      under the same anaesthetic conditions. After induction of anaesthesia with
      etomidate and fentanyl, neuromuscular blockade was monitored by recording the
      electromyographic response of the adductor pollicis muscle to a supramaximal
      train-of-four (TOF) stimulation of the ulnar nerve at 2 Hz for 2 s at 20-s
      intervals. Intubation was performed when more than 90% muscle relaxation was
      achieved, thereafter anaesthesia was maintained with 70% nitrous oxide in oxygen
      and isoflurane 0.5% end-tidal. Mean onset of action was significantly faster
      following rocuronium (86 +/- 44.9 s) (mean +/- SD) compared with atracurium
      (126.3 +/- 61.0 s). Clinical duration with rocuronium was 22.8 +/- 5.31 min and
      thus significantly shorter than that of atracurium, which was 31.5 +/- 6.01 min.
      A statistically significant difference between rocuronium and atracurium also had
      been found for recovery of T1 to 50%, 75% and 90% as well as for the time taken
      to a TOF ratio of 70%. The recovery index for rocuronium and atracurium was not
      significantly different with 9.2 +/- 3.43 min and 10.9 +/- 2.65 min,
      respectively. Thus, rocuronium may be more advantageous than atracurium for short
      lasting surgical procedures in young children.

PMID- 9649991
TI  - Checking the anaesthetic machine: self-reported assessment in a university
      hospital.
AB  - Checking the anaesthetic machine before its daily use is essential. The aim of
      our study was to evaluate, through the use of an anonymous questionnaire, how the
      anaesthetists of our institution (physicians and nurses) report their daily
      checking. Sixty-three questions were used to ask the participants how frequently
      they checked the main components of the anaesthetic machine; the answers were
      evaluated with a score (0-3). The overall response rate was 78%, nurses; rate
      being lower than physicians' rate. Nurses obtained a higher global score, which
      raises the question of different adherence to guidelines by nurses and
      physicians. Moreover, questions in relation to gas supply were badly scored by
      all participants, which should alert us to reinforce theoretical and practical
      training in these items. Finally, although the methodology used in this survey
      could raise the question of the best way to evaluate the actual checkout
      procedure, self-reported assessment remains an alternative to more complex and
      expensive methods, such as an observer or a video evaluation.

PMID- 9649992
TI  - Haemodynamic effects of repeated epidural test-doses of adrenaline in the chronic
      maternal-fetal sheep preparation.
AB  - A randomized crossover study was designed using the chronically instrumented
      pregnant sheep preparation to study the possible effects of epidural injection of
      adrenaline as a single compound on the circulation of mother and fetus. Three
      consecutive identical doses of adrenaline were administered epidurally with a 30
      min interval between treatments. In a randomized crossover fashion two dosages
      (10 and 15 micrograms) were tested on different days. The day after the last
      epidural experiment the same doses of adrenaline were given intravenously (i.v.).
      Between the two i.v. doses a 30 min interval was allowed for values to return to
      baseline. Twenty-seven experiments were performed in eight ewes. Epidural
      administration of adrenaline did not affect maternal mean arterial pressure,
      maternal heart rate, uterine blood flow, fetal mean arterial pressure, fetal heat
      rate, or maternal and fetal blood gases and acid-base status. After i.v.
      administration of adrenaline the uterine blood flow decreased in a dose-dependent
      fashion, but the other haemodynamic variables were not affected. In conclusion,
      this study indicates that consecutive epidural injections of adrenaline have no
      significant effect on maternal and fetal haemodynamic responses, uterine blood
      flow, blood gases and acid-base status in the gravid ewe. However, an i.v.
      injection of 10 or 15 micrograms adrenaline decreases the uterine blood flow and
      could compromise the fetus.

PMID- 9649993
TI  - Adsorption of desflurane from the scavenging system during high-flow and minimal
      flow anaesthesia by zeolites.
AB  - Application of high-silica zeolites in a special adsorber allows complete
      selective adsorption of the inhalation anaesthetic desflurane from the outlet
      port of the scavenging system of the anaesthesia machine. In comparison with
      charcoal filters, zeolites allow almost complete desorption at moderate
      temperatures followed by condensation of the desflurane to the liquid phase. The
      adsorption of scavenged desflurane by zeolites was measured in 13 patients. The
      duration of the anaesthesia was between 70 and 130 min. A minimal-flow regime
      (0.5 L min-1 fresh gas inflow) was used for maintenance in seven patients and a
      higher-flow regime (3 L min-1 fresh gas flow) was used for maintenance in six
      patients. In minimal-flow anaesthesia, 62% of the delivered desflurane was
      adsorbed by the zeolite while 86% of the delivered desflurane was adsorbed in
      higher-flow anaesthesia. Preliminary results show that about 85% of the adsorbed
      desflurane could be recovered as liquid with high purity via desorption.

PMID- 9649994
TI  - Value of oropharyngeal Mallampati classification in predicting difficult
      laryngoscopy among obese patients.
AB  - The prediction of difficult intubation in obese patients was investigated by co
      estimating the degree of visibility of oropharyngeal structures in conjunction
      with the respective body mass index. Data were collected prospectively in a
      series of 1833 consecutive adult patients. Body mass index (BMI) in kg m-2 was
      used as a measure of obesity (morbid: > 40, moderate: 30-40, no obesity: < 30).
      The oropharyngeal class findings were assessed using the original methodology as
      well as by a modification requiring the tongue to be pulled forward by the
      examiner. Difficult intubation was defined as inadequate exposure of the glottis
      by direct laryngoscopy. Both oropharyngeal class methodologies were of equal
      sensitivity, whereas the modified technique presented a significantly higher
      positive predictive value (50.0% vs. 37.2%, P < 0.01). Statistical analysis
      revealed an increased risk of difficult laryngoscopy among obese patients
      compared with subjects with normal body mass index (20.2% vs. 7.6%, P < 0.001).
      When obesity is estimated with respect to oropharyngeal class the positive
      predictive value is greatly improved (66.7% vs. 20.2%, P < 0.001). We conclude
      that obesity which is associated with a disproportionately large base of the
      tongue, is a predisposing factor for difficult laryngoscopy.

PMID- 9649995
TI  - Changes in plasma catecholamine concentrations and haemodynamic effects of
      rocuronium and vecuronium in elderly patients.
AB  - Rocuronium administration may cause tachycardia and an increase in cardiac index.
      Pancuronium, another steroidal non-depolarizing muscle relaxant, augments release
      of, and blocks re-uptake of catecholamines at adrenergic nerve endings. This
      study compared the haemodynamic effects of, and changes in catecholamine
      concentrations following administration of vecuronium (0.12 mg kg-1) or
      rocuronium (0.9 mg kg-1) to elderly patients. Thirty patients, 65 years or older,
      not receiving beta-blockers, were studied. During thiopentone, fentanyl, nitrous
      oxide anaesthesia, either rocuronium (0.9 mg kg-1) or vecuronium (0.12 mg kg-1)
      was administered, according to random allocation. In all 30 patients, blood
      pressure and heart rate were measured before induction of anaesthesia,
      immediately and 1 min after induction, 1 and 2 min after muscle relaxant
      administration, and immediately, 1 and 2 min after tracheal intubation. In the
      latter 20 patients, samples for plasma catecholamine estimation were obtained
      prior to, and 1 min after muscle relaxant administration and 1 min after tracheal
      intubation. Blood pressure and heart rate were similar in the two groups
      throughout the study. Plasma noradrenaline concentrations were similar in the
      vecuronium and rocuronium groups prior to muscle relaxant administration
      (589(SD240) and 444(SD213) pg mL-1, respectively), 1 min after muscle relaxant
      administration (602(SD220) and 520(SD392) pg mL-1, respectively) and 1 min after
      tracheal intubation (597(SD351) and 440(SD181) pg mL, respectively). There was no
      significant change in either plasma noradrenaline or adrenaline concentrations in
      either group following muscle relaxant administration or tracheal intubation. The
      use of rocuronium (0.9 mg kg-1) in elderly patients does not result in a
      clinically significant change in heart rate, blood pressure or plasma
      catecholamine concentration.

PMID- 9649996
TI  - Efficacy of thoracic epidural analgesia following laparoscopic cholecystectomy.
AB  - This study was undertaken to determine whether epidural analgesia has any benefit
      for post-operative pain relief in patients undergoing laparoscopic
      cholecystectomy. Patients were randomly assigned to receive post-operative
      epidural analgesia with a morphine-bupivacaine combination (Group A, n = 22) or
      placebo (saline) (Group B, n = 22). The same standard general anaesthetic
      technique, which consists of nitrous oxide and isoflurane in oxygen was used.
      Analgesia was assessed using visual analogue pain scores (0-10 cm). The
      evaluation was carried out 24 and 48 h post-operatively. At 24 h after
      anaesthesia, pain scores in Group A (2.3 +/- 1.2) were lower than those in Group
      B (4.4 +/- 1.5) (P < 0.05). However, at 48 h post-operatively, no difference in
      scores was observed between the two groups. In conclusion, epidural analgesia
      with a morphine-bupivacaine combination improves pain relief during the first 24
      h following laparoscopic cholecystectomy.

PMID- 9649997
TI  - Changes in adhesion molecule expression and oxidative burst activity of
      granulocytes and monocytes during open-heart surgery with cardiopulmonary bypass
      compared with abdominal surgery.
AB  - Cardiac and major abdominal surgery are associated with granulocytosis in
      peripheral blood. The purpose of the present study was to describe the
      granulocyte and monocyte oxidative burst and the expression of adhesion molecules
      following cardiac surgery with cardiopulmonary bypass and abdominal surgery. The
      ability to respond with an oxidative burst was measured by means of flow
      cytometry using 123-dihydrorhodamine. The adhesion molecules CD11a/CD18,
      CD11c/CD18, CD44 were measured using monoclonal antibodies. Blood samples from
      eight patients undergoing open-heart surgery were taken before surgery, 1, 5, 10
      and 20 min after aortic clamping, and then 1, 5, 10 and 20 min and 1, 2 and 3 h
      after declamping. Samples from eight patients undergoing abdominal surgery were
      taken before surgery, at the end of surgery, and 2 and 3 h post-operatively. A
      decrease in number of granulocytes and monocytes during cardiopulmonary bypass
      was observed. The percentage of CD11a-positive granulocytes increased from 30%
      pre-operatively to 75% following cardiopulmonary bypass, while CD44-positive
      granulocytes increased from 5% to 13%. Despite the extent of the changes, these
      were not significant. The oxidative burst of the granulocytes and monocytes
      decreased after declamping to 15% and 27% of initial values in vitro. Several
      hours after surgery, there was no significant difference between the two groups.
      These results can be explained by a granulocyte and monocyte refractory response
      developing subsequent to an increased per-operative oxidative burst activity, and
      the induction of adhesion molecules on granulocytes associated with the
      cardiopulmonary bypass and surgery. In conclusion, open-heart surgery with
      cardiopulmonary bypass was associated with a rapid and pronounced activation of
      leukocytes which may play a role in reperfusion injury.

PMID- 9649998
TI  - Acute pain services in Europe: a 17-nation survey of 105 hospitals. The EuroPain
      Acute Pain Working Party.
AB  - A 17-nation survey was undertaken with the aim of studying the availability of
      acute pain services (APS) and the use of newer analgesic techniques, such as
      epidural and patient-controlled analgesia (PCA). A questionnaire was mailed to
      selected anaesthesiologists in 105 European hospitals from 17 countries.
      Depending on the population, between five and ten representative hospitals from
      each country were selected by a country coordinator. A total of 101 (96.2%)
      completed questionnaires were returned. A majority of respondents were
      dissatisfied with pain management on surgical wards. Pain management was better
      in post-anaesthesia care units (PACUs); however, 27% of participating hospitals
      did not have PACUs. There were no organized APS in 64% of hospitals, although
      anaesthesiologists from chronic pain centres were available for consultation. In
      the hospitals that had APS, the responsible person for the APS was either: (1) a
      junior anaesthesiologist (senior anaesthesiologist available for consultation);
      or (2) a specially trained nurse (supervised by consultant anaesthesiologists).
      Many anaesthesiologists were unable to introduce techniques such as PCA on wards
      because of the high equipment costs. Although 40% of hospitals used a visual
      analogue scale (VAS) or other methods for assessment of pain intensity, routine
      pain assessment and documenting on a vital sign chart was rarely practised. There
      was a great variation in routines for opioid prescription and documentation
      procedures. Nursing regulations regarding injection of drugs into epidural and
      intrathecal catheters also varied considerably between countries. This survey of
      105 hospitals from 17 European countries showed that over 50% of
      anaesthesiologists were dissatisfied with post-operative pain management on
      surgical wards. Only 34% of hospitals had an organized APS, and very few
      hospitals used quality assurance measures such as frequent pain assessment and
      documentation. There is a need to establish organized APS in most hospitals and
      also a need for clearer definition of the role of anaesthesiologists in such APS.

PMID- 9649999
TI  - Anaesthetic management for caesarean section combined with removal of
      phaeochromocytoma.
AB  - In this case report, the anaesthetic management for a removal of
      phaeochromocytoma undertaken immediately following Caesarean section is
      described. A 32-year-old female patients was given epidural anaesthesia for
      Caesarean section, and thereafter, general anaesthesia for a resection of
      phaeochromocytoma. During surgery, phentolamine, nitroglycerine and prostaglandin
      E1 were electively administered to decrease blood pressure and heart rate. A live
      infant was delivered and the supra-adrenal tumour was excised successfully. The
      patient's post-operative recovery was uneventful.

PMID- 9650000
TI  - Cerebral aneurysm surgery in a patient with phaeochromocytoma.
AB  - This case report describes the peri-operative management of a 48-year-old woman
      with three cerebral aneurysms and phaeochromocytoma. The pharmacological and
      anaesthetic management of such patients is complex, and needs to be managed
      carefully by titrating anaesthetic agents and vasoactive drugs. The primary
      concern is the maintenance of cerebral perfusion pressure and autoregulation
      throughout the procedure, although these states cannot be monitored directly. The
      patient survived the operation neurologically intact, and it is presumed that the
      course of management which was chosen helped to achieve this result.

PMID- 9650001
TI  - Intestinal pseudo-obstruction associated with oral morphine.
AB  - Morphine is recommended as the strong opioid of choice by the World Health
      Organization (WHO) for cancer pain management. It is associated with delay in
      gastro-intestinal transit; as a result, patients may experience marked
      constipation. We describe a case of intestinal pseudo-obstruction associated with
      the use of oral morphine in a terminally ill cancer patient.

PMID- 9650002
TI  - Fatal air embolism: a complication of manipulation of a cavitating metastatic
      lesion of the liver.
AB  - A patient undergoing emergency laparotomy for an acute abdomen developed fatal
      air embolism as a result of surgical manipulation of a cavitating metastatic
      lesion of the liver. The diagnosis was made at postmortem examination. This cause
      of air embolism has apparently not been reported before. The causes and
      management of air embolism are briefly reviewed. It is concluded that in
      exceptional circumstances when intubated patients are sent to a recovery area,
      the continuation of CO2 monitoring into the post-operative period should be
      considered.

PMID- 9650003
TI  - Use of the laryngeal mask during emergence from anaesthesia.

PMID- 9650004
TI  - Treating severe tetanus with muscle paralysis and intermittent positive pressure
      ventilation.

PMID- 9650005
TI  - Repeated measures ANOVA for responses developing over time.

PMID- 9650006
TI  - Relevance of erythrocyte Na+/Li+ countertransport measurement in essential
      hypertension, hyperlipidaemia and diabetic nephropathy: a critical review.
AB  - In this review the usefulness of the measurement of erythrocyte Na+/Li+
      countertransport (Na+/Li+ CT) activity is evaluated. In particular, the
      association between enhanced erythrocyte Na+/Li+ CT activity and essential
      hypertension, hyperlipidaemia and diabetic nephropathy is discussed. The
      conclusion of this review is that elevated erythrocyte Na+/Li+ CT activity is
      associated with essential hypertension and hyperlipidaemia. A relationship
      between Na+/Li+ CT activity and diabetic nephropathy is less evident. Despite a
      significant link of Na+/Li+ CT activity with hypertension and hyperlipidaemia,
      the diagnostic significance of Na+/Li+ CT activity is low. This is due to the
      large overlap between the results of control subjects and patients. The factors
      that contribute to this broad range are discussed in detail.

PMID- 9650007
TI  - Effects of parathyroid hormone and serum calcium on the phenotype and function of
      mononuclear cells in patients with primary hyperparathyroidism.
AB  - BACKGROUND: Several studies have demonstrated specific influence of parathyroid
      hormone (PTH) on immune parameters, especially on T- and B-cell function,
      migration of polymorphonuclear leucocytes (PMNLs) and antibody synthesis, in
      patients with secondary hyperparathyroidism and chronic renal failure and
      recently also in patients with primary hyperparathyroidism (pHPT). METHODS: We
      therefore examined 12 patients with pHPT before and 6 months after
      parathyroidectomy (PTX) and nine sex- and age-matched control subjects to
      determine the impact of PTH and serum calcium concentrations on several immune
      parameters, including (a) serum concentrations of immunoglobulins, (b)
      immunophenotype of peripheral blood lymphocytes, (c) phytohaemagglutinin (PHA)
      induced lymphocyte proliferation and (d) monocytic surface marker expression.
      RESULTS: Serum concentrations of immunoglobulins (IgG, IgA, IgM) were unaffected
      by elevated serum PTH and calcium levels. T lymphocytes (CD3), B lymphocytes
      (CD19), NK cells (CD16/56) and monocytes (CD16) revealed a normal distribution
      and were not different before and after PTX in patients with pHPT when compared
      with the control group. CD4+ T-helper lymphocytes were significantly elevated pre
      and post-operatively in patients with pHPT. The lymphocyte proliferation
      response to PHA in the highest concentration (12.5 micrograms L-1) tested was
      significantly suppressed in patients with pHPT preoperatively when compared with
      the patients post-operatively and the control group. In addition, both CD4+ and
      CD8+ lymphocytes showed a lower expression of activation markers, interleukin 2
      (IL-2) receptor (CD25) and transferrin receptor (CD71), which could be partially
      restored 6 months after PTX, but did not reach normal values. CONCLUSION: In
      summary, in contrast to the findings in patients with secondary HPT, pHPT appears
      to be associated with less alterations of immune functions. Chronically elevated
      serum PTH and calcium concentrations in patients with pHPT induce a higher
      percentage of CD4+ helper T lymphocytes and a suppressed lymphocyte response to
      PHA as well as a reduced expression of activation markers on peripheral blood
      lymphocytes.

PMID- 9650008
TI  - Oral guar gum treatment of intrahepatic cholestasis and pruritus in pregnant
      women: effects on serum cholestanol and other non-cholesterol sterols.
AB  - BACKGROUND: Our aim was to investigate whether intestinal binding of bile acids
      by guar gum, a dietary fibre, relieves cholestasis and pruritus in intrahepatic
      cholestasis of pregnancy. METHODS: Forty-eight pregnant women with cholestasis
      and pruritus were randomized double-blind to guar gum and placebo until the time
      of delivery, and 20 healthy pregnant women were used as control subjects. The
      pruritus score and serum bile acids, lipids and non-cholesterol sterols were
      measured at baseline, at least 2 weeks after treatment, just before delivery and
      up to 4 weeks after delivery. RESULTS: The increase in serum bile acids and
      worsening of pruritus were prevented by guar gum in relation to placebo (P <
      0.05). Serum cholesterol was unchanged, but increased cholesterol precursor
      sterol values suggested that cholesterol synthesis was increased by guar gum.
      Serum cholestanol proportion, an indicator of cholestasis, was related to
      pruritus but was unaffected by guar gum. CONCLUSION: We conclude that in
      intrahepatic cholestasis of pregnancy and pruritus, guar gum treatment is
      beneficial in relieving pruritus, even although indicators of cholestasis are
      only partially reduced.

PMID- 9650009
TI  - Cellular and molecular characteristics of inflammation in chronic bronchitis.
AB  - METHODS: To examine the inflammatory process in chronic bronchitis, we evaluated
      the cell and cytokine profile in bronchoalveolar lavage fluid from 12 chronic
      bronchitis patients who smoked, six chronic bronchitis patients who did not
      smoke, 10 subjects control subjects without pulmonary diseases who smoked and
      eight control subjects who did not smoke. RESULTS: Chronic bronchitis patients
      who smoked had increased numbers of macrophages, neutrophils, eosinophils, mast
      cells and activated CD8+ T lymphocytes and predominantly expressed interleukin-8,
      tumour necrosis factor alpha and interleukin-2 genes and proteins. The number of
      macrophages and neutrophils and the expression of interleukin 8 were also
      increased in control subjects who smoked compared with healthy subjects who did
      not smoke. Chronic bronchitis patients who did not smoke had increased numbers of
      eosinophils, mast cells and activated CD4+ T lymphocytes and predominantly
      expressed interleukin-5 and granulocyte-macrophage colony-stimulating factor
      genes and proteins. CONCLUSION: Thus, the cellular and molecular characteristics
      of the inflammatory process in chronic bronchitis patients who smoke and do not
      smoke are different, suggesting a different pathogenesis of the disease.

PMID- 9650010
TI  - Expression of tenascin is related to angiogenesis in pre-eclampsia.
AB  - METHODS: Ten samples of decidua basalis from pre-eclamptic women and 10 from
      healthy primigravid women subjected to caesarean section (control tissues) were
      investigated immunohistochemically for changes in angiogenesis and expression of
      tenascin, an extracellular matrix protein thought to modulate angiogenesis. In
      addition, pre-eclamptic and control samples were grafted onto the chick embryo
      chorioallantoic membrane (CAM) to study their possible angiogenic activity in
      vivo. RESULTS: Although the microvessel area was low in control samples, it
      increased significantly in the pre-eclamptic decidua. In parallel, the area
      covered by tenascin staining underwent a significant expansion that was highly
      correlated with the microvessel area. Angiogenic activity was assessed both
      macroscopically and microscopically on histological sections 4 days after
      grafting. In contrast to control samples, pre-eclamptic decidua induced an
      intense capillary growth, and numerous capillaries converging towards the implant
      and forming a spoke-wheel pattern were evident. Histological examination using a
      planimetric point-count method showed that microvessel counts in the CAM area
      under and around the pre-eclamptic implants were significantly higher than those
      of control samples. Again, the extracellular matrix of nearby microvessels was
      strongly immunoreactive with tenascin. CONCLUSION: It is suggested that, unlike
      normal decidua, pre-eclamptic decidua displays an intense, autonomous angiogenic
      activity, probably mediated by tenascin in addition to its own angiogenic
      factors.

PMID- 9650011
TI  - Accumulation of chylomicron remnants in homozygous subjects with familial
      hypercholesterolaemia.
AB  - BACKGROUND: Post-prandial lipoprotein kinetics were investigated in subjects who
      lack functioning low-density lipoprotein (LDL) receptors [homozygous familial
      hypercholesterolaemia (FH)]. METHODS: An oral fat load was given, and chylomicron
      plasma kinetics was determined by monitoring the clearance of triglyceride,
      retinyl palmitate and apolipoprotein B48, calculated as the area under the curve,
      for 7.5 h. In addition, the binding and uptake of chylomicron remnants by
      fibroblasts of FH and control subjects were assessed in vitro. RESULTS: Based on
      the plasma kinetics of chylomicron triglyceride, retinyl palmitate and
      apolipoprotein B48 after a lipid meal, chylomicron clearance was found to be
      substantially delayed compared with normolipidaemic control subjects. Consistent
      with involvement of the LDL receptor in chylomicron clearance, binding and uptake
      of chylomicron remnants by fibroblasts of FH subjects was found to be
      substantially less than in cells from control subjects. CONCLUSION: This study
      shows that, in addition to LDL, chylomicron metabolism is severely impaired in FH
      and that the LDL receptor is significantly involved in the clearance of post
      prandial lipoproteins. Moreover, this study raises the possibility that in FH,
      and in other disorders in which LDL receptor expression is reduced, atherogenesis
      might be a post-prandial disease.

PMID- 9650012
TI  - Lack of relationship between the P1A1/P1A2 polymorphism of platelet glycoprotein
      IIIa and premature myocardial infarction.
AB  - BACKGROUND: The P1A1/P1A2 polymorphism of the platelet glycoprotein IIIa has been
      variably associated with an increased risk of coronary thrombosis. MATERIALS: We
      investigated the linkage between the P1A1/P1A2 polymorphism and the risk of
      myocardial infarction in 98 patients who suffered their first myocardial
      infarction at the age of 45 years or less and 98 well-matched control subjects
      without coronary artery disease. Lipid parameters were measured using
      conventional methods of clinical chemistry; P1A genotypes were determined by
      polymerase chain reaction and restriction enzyme digestion. RESULTS: There was no
      significant difference in the prevalence of P1A2-positive genotypes (either
      P1A1/P1A2 or P1A2/P1A2) between patients and control subjects (chi 2 = 0.66, d.f.
      = 1, P = 0.41). CONCLUSIONS: These results suggest that the P1A2 polymorphism of
      the platelet glycoprotein IIIa does not contribute to the genetic susceptibility
      to premature myocardial infarction.

PMID- 9650013
TI  - Sodium selenite and N-acetylcysteine in antiretroviral-naive HIV-1-infected
      patients: a randomized, controlled pilot study.
AB  - BACKGROUND: The aim of this work was to study the effects of combined oral
      administration of N-acetylcysteine (NAC) and sodium selenite (Se) on plasma
      glutathione (GSH), lymphocyte subpopulations and viral load in asymptomatic human
      immunodeficiency virus (HIV)-infected patients. METHODS: We used a prospective,
      randomized and controlled therapy trial with partial crossover. Twenty-four
      antiretroviral-naive HIV-infected outpatients at Centers for Disease Control
      (CDC)'93 stages I and II were randomized to receive the antioxidant combination
      NAC 600 mg t.i.d. and Se 500 micrograms per day for either 24 weeks (group A, n =
      13) or from the end of week 12 (group B, n = 11) until the end of week 24. Thus,
      group B served as untreated control during the first 12 weeks. RESULTS: There was
      (a) a trend towards an increase in the percentage of CD4+ lymphocytes after 6
      weeks (P = 0.08); (b) an increase in the CD4/CD8 ratio after 6 and 12 weeks (P =
      0.02 and P = 0.04 respectively); and (c) a decrease in the absolute CD8/CD38
      count and percentage of lymphocytes after 6 weeks (P = 0.002 and P = 0.033
      respectively) and 12 weeks (P = 0.033, P = 0.1 respectively) in group A compared
      with the control period of group B. The effects observed in group A were,
      however, not paralleled to the same extent by group B after crossing-over to
      treatment after 12 weeks. In addition, erythrocyte glutathione peroxidase (GSH
      Px) activity and GSH, glutathionedisulphide (GSSG) concentrations and the
      reduced/total GSH ratio were not affected by the treatment. Serum selenium levels
      increased significantly (P < 0.001) upon treatment. Viral load was not altered.
      CONCLUSIONS: The changes in lymphocyte subsets after NAC/Se treatment were not
      comparable to those after standard antiretroviral drug therapy. This, however,
      does not preclude per se possible benefits of antioxidant supplementation in HIV
      disease.

PMID- 9650014
TI  - Growth effects of alpha-interferon but not of bombesin or angiotensin II are
      mediated by activation of STAT proteins.
AB  - BACKGROUND: The recently discovered Jak/STAT signal transduction pathway is
      associated with cytokine or growth factor receptors; whether members of the G
      protein-coupled receptor superfamily also activate this pathway is not yet clear.
      As a first member, the angiotensin (AT)1A receptor has been demonstrated to
      phosphorylate Jak and STAT proteins. Bombesin, a neurotransmitter and growth
      factor in many cells and tissues, activates its G protein-coupled receptor and in
      addition phosphorylates proteins that might be members of the Jak/STAT family.
      This study investigated whether bombesin- or angiotensin-mediated growth effects
      are associated with STAT protein activation. METHODS: Functional receptors were
      characterized using ligand-binding studies, second-messenger activation and
      determination of ligand-mediated growth effects. STAT protein activation was
      analysed by electrophoretic mobility shift assay (EMSA) using labelled DNA
      response elements recognizing all known STAT proteins. RESULTS: Functional
      bombesin receptors mediating mitogenic effects were demonstrated on Swiss 3T3
      fibroblasts, human melanoma cells (A375-6) and primary human lung fibroblasts;
      however, bombesin-related STAT protein activation was not observed by EMSA.
      Interferon-alpha typically activated a STAT1-STAT2-p48 heterotrimer, as well as
      STAT1-3 hetero- and homodimers in human melanoma cells and significantly
      inhibited growth of this cell line in vitro. Functional AT1A receptors on primary
      rat cardiac fibroblasts mediated angiotensin-stimulated growth effects but, in
      contrast to recently published data, did not activate any known STAT protein.
      CONCLUSION: Interferon alpha-stimulated growth inhibition is mediated by
      activation of the Jak/STAT pathway, whereas bombesin or AT1A receptor-mediated
      effects on cellular proliferation do not involve phosphorylation of STAT
      proteins.

PMID- 9650015
TI  - Comparison of three fatty meals in healthy normolipidaemic men: high post
      prandial retinyl ester response to soybean oil.
AB  - BACKGROUND: Oral fat tolerance tests (FTTs) have been widely used as a tool to
      investigate post-prandial lipaemia. However, there is no consensus regarding the
      type and amount of fat used in the tests. METHODS: We compared three commonly
      used FTTs, each containing 63 g of fat: a mixed meal, a liquid cream meal and a
      liquid soybean oil meal. The study group consisted of 10 healthy normolipidaemic
      men. We measured triglycerides (TGs), retinyl esters (REs), apolipoprotein E
      (apoE), apolipoprotein B-48 (apoB-48) and apolipoprotein B-100 (apoB-100) in
      plasma and in triglyceride-rich lipoprotein (TRL) fractions separated by density
      gradient ultracentrifugation at baseline and 3, 4, 6, and 8 h after the FTTs.
      RESULTS: We observed similar TGs, apoE, apoB-48 and apoB-100 responses after all
      three FTTs, despite the different fatty acid composition of the meals. In
      contrast, the commonly used marker for exogenous particles, RE, differed clearly
      when polyunsaturated (soybean oil) and saturated fat (cream or mixed meal) were
      used. The RE response in plasma (P < 0.005, repeated measures ANOVA), in
      chylomicrons (P < 0.013) and in very low-density lipoprotein (VLDL) 1 (P <
      0.017), as well as the RE area under the incremental curve in plasma and
      chylomicron fractions, were markedly increased after the soybean oil meal
      compared with the mixed meal and cream meal tests. The peak of RE response
      occurred parallel to the responses of other markers (i.e. TG or apoB-48) of post
      prandial TRL during soybean oil meal. In contrast, RE peak concentration was
      delayed after saturated fat-containing meals. After soybean oil, FTT plasma
      cholesterol concentration was lower and the chylomicron cholesterol concentration
      was higher compared with mixed or cream meals, but no differences were detected
      in post-prandial high-density lipoprotein (HDL)-cholesterol concentration.
      CONCLUSION: When the amount of fat is similar, post-prandial responses of TG,
      apoE, apoB-48, apoB-100 and HDL-cholesterol were comparable after different FTTs.

PMID- 9650016
TI  - Expression of cGMP-dependent protein kinase I and its substrate VASP in
      neointimal cells of the injured rat carotid artery.
AB  - BACKGROUND: Neointimal fibroproliferative lesions after balloon angioplasty
      remain a major clinical problem, frequently leading to restenosis of initially
      successfully dilated coronary arteries. The cGMP-dependent protein kinase type I
      (cGMP-PK I) and its substrate vasodilator-stimulated phosphoprotein (VASP),
      molecular targets of the atrial natriuretic factor (ANF) and nitric oxide (NO)
      signalling pathways, are likely to be involved in various aspects of vascular
      wall regulation and restenosis formation. METHODS: To investigate the occurrence
      of cGMP-PK I and VASP in neointimal cells in situ, we performed
      immunohistochemistry and immunoblotting experiments on denuded rat carotid
      arteries. RESULTS: Although the soluble cGMP-PK I showed a homogeneous
      distribution throughout the neointima, VASP apparently was more concentrated in
      smooth muscle cells (SMCs) lining the artery lumen, possibly reflecting enhanced
      growth factor stimulation of luminal SMCs. The membrane-associated cGMP-PK type
      II could not be detected in both the non-injured vessel wall and the restenotic
      tissue. CONCLUSION: The presence of both cGMP-PK I and VASP, major regulators of
      the actin cytoskeleton and cell motility, in neointimal tissue suggest that this
      emerging signal transduction pathway could be a target for the regulation and
      control of restenosis.

PMID- 9650017
TI  - Pneumocystis carinii induces interleukin 6 production by an alveolar epithelial
      cell line.
AB  - BACKGROUND: Pneumocystis carinii (PC) infection often results in severe pneumonia
      in immunocompromised patients. Attachment of PC organisms to alveolar epithelial
      cells is a hallmark of PC pneumonia; however, few studies have investigated the
      response of alveolar epithelial cells to PC infection. METHODS: Interleukin 6 (IL
      6) is a multifunctional cytokine that is produced by alveolar epithelial cells in
      response to a variety of stimuli. Our investigation was undertaken to determine
      whether PC organisms induce production of IL-6 by alveolar epithelial cells and
      to determine the effect of IL-6 on PC attachment. RESULTS: Incubation of the
      human alveolar epithelial cell line, A549, with PC organisms resulted in a
      significant increase in IL-6 secreted into the cell culture media. Time-course
      studies showed that IL-6 production was detected as soon as 2 h after addition of
      PC and continued up to 48 h of exposure. Further studies demonstrated that
      preincubation of A549 cells with IL-6 resulted in a concentration-dependent
      increase in both A549 cell production of fibronectin and PC attachment.
      CONCLUSION: Thus, PC attachment to an alveolar epithelial cell line results in
      epithelial cell production of IL-6, which can act to further increase PC
      attachment. This may provide an important mechanism whereby PC organisms directly
      affect the host response to PC infection.

PMID- 9650018
TI  - Intestinal epithelial hyperpermeability. Mechanisms and relevance to disease.
AB  - Pathologic increases in intestinal permeability to hydrophilic macromolecules has
      been identified in a number of clinical conditions. The significance of gut
      barrier dysfunction as a clinical issue remains to be delineated, although it
      seems likely that alterations in intestinal epithelial permeability play a
      causative role in a number of conditions ranging from inflammatory bowel disease
      to the development of complications after cardiopulmonary bypass. It is unlikely
      that any one mechanism can account for all cases of intestinal hyperpermeability.
      Rather, it is more probable that myriad factors or combinations of factors,
      including mesenteric ischemia and cytokine-induced phenomena, lead to alterations
      in permeability in different clinical entities. Nevertheless, from a purely
      mechanistic standpoint, some common themes, notably the role of ATP depletion,
      increases in [Ca2+]i, and cytoskeletal derangements in enterocytes, have emerged
      as being particularly important.

PMID- 9650019
TI  - The aging gut. Nutritional issues.
AB  - With improvements in health care, living standards, and socioeconomic status,
      more adults are living to old age. As the population ages, it is increasingly
      important to understand the factors that affect the nutritional status and thus
      the health status of older adults. Many factors contribute to inadequate
      nutrition, including health status, financial capacities, mobility, exercise, and
      physiologic needs. This article considered only the potential changes in
      nutritional needs because of alterations in the gastrointestinal tract owing to
      aging. One of the most remarkable changes with aging is the frequent development
      of atrophic gastritis and the inability to secrete gastric acid. This process
      affects approximately a third of older adults in the United States and only
      recently was recognized to be due to infection by H. pylori in the majority of
      cases. The lack of gastric acid in atrophic gastritis may lead to small
      intestinal bacterial overgrowth and influences the absorption of a variety of
      micronutrients, including iron, folate, calcium, vitamin K, and vitamin B12.
      Lactose maldigestion is a frequent condition in older adults and is extremely
      common worldwide. The intolerance of dairy products leads to avoidance of these
      foods and likely contributes to the development of osteopenia. Overall, the small
      intestine and pancreas undergo astonishingly few clinically significant changes
      with aging. The relative preservation of overall gastrointestinal function with
      aging is likely due to the large reserve capacity of this multiorgan system.
      Further research is needed to define the precise nutritional needs for older
      adults because simple extrapolation of values from younger adults is now
      recognized to be insufficient. In addition, it is no longer acceptable to define
      adequate nutriture in terms of amounts of vitamins needed to maintain serum
      levels of a nutrient. Further RDAs must consider the functional implications of
      adequate nutrition. Nutrients in the elderly will be measured as to whether they
      result in improvements in markers of chronic disease such as homocysteine or,
      most importantly, in the prevention of chronic disease such as osteoporosis and
      cardiovascular disease.

PMID- 9650020
TI  - Diet, nutrients, and gastrointestinal cancer.
AB  - Tobacco and alcohol use are strong risk factors for cancer of the upper
      gastrointestinal tract. Saturated fat and red meat intake also appear to increase
      the risk of colorectal cancer. The strongest and most consistent dietary
      protective factors for gastrointestinal cancer are vegetables and fruits. Some
      micronutrients show beneficial effects, but the degree of protection is less than
      that observed from whole plant foods. Substantial decreases in the morbidity and
      mortality from gastrointestinal cancer could occur with more widespread adoption
      of dietary guidelines designed for cancer prevention.

PMID- 9650021
TI  - Nutritional assessment.
AB  - Nutritional status is a dynamic entity that changes because of interactions
      between nutrient intake and absorption and requirements and disease. Clinically
      relevant nutritional assessment should determine whether the patient's
      nutritional status will decline in the absence of nutritional support. In
      addition, such assessment should predict complications in the absence of
      nutritional intervention. The role of different techniques--clinical body
      compositional, and functional--is discussed in this context.

PMID- 9650022
TI  - Enteral nutrition.
AB  - This article briefly reviews the literature supporting the use of enteral
      nutrition, which appears to be the preferred method of nutritional support in
      critically ill patients. Patients who benefit the most from this type of support,
      as well as the administration and route preferences in enteral nutrition, are
      discussed. In addition, the different types of enteral formulas and the more
      frequently associated complications that occur with tube feedings are reviewed.

PMID- 9650023
TI  - Nutrient pharmacotherapy for gut mucosal diseases.
AB  - The use of nutrients for pharmacotherapy is a recent advance in the treatment of
      gastrointestinal disorders or alterations of gut function and structure.
      Nutrients may have a direct effect on the gut, or may enhance the response to
      medications. Alternatively, pharmacologic agents may improve the absorption of
      nutrients. Potentially, pharmacotherapy may be an adjunct to the traditional
      approach used in the treatment of compromised patients.

PMID- 9650024
TI  - Nutrient antioxidants in gastrointestinal diseases.
AB  - Oxidative stress appears to play a role in the pathogenesis of a number of
      gastrointestinal disease states, including pancreatitis; gastric and duodenal
      ulcer disease; IBD; gastric, esophageal, and colon cancers; and hepatic injury
      secondary to alcohol, metal storage disorders, hepatitis, and
      ischemia/reperfusion injury. The nutritional antioxidants are attractive
      potential therapeutic and chemopreventive agents because they are inexpensive and
      have a relatively low toxicity profile. A word of caution should be noted: Some
      antioxidants, such as vitamin C, can be prooxidant under certain conditions, and
      systemically altering the redox state may have untoward effects on the
      inflammatory response in certain disease states. Thus, at the current time,
      antioxidant therapy should be restricted to randomized, controlled clinical
      trials, in which treatment effects can be closely monitored, and therapeutic
      efficacy can be determined with scientific accuracy.

PMID- 9650025
TI  - Nutritional management in acute and chronic pancreatitis.
AB  - Patients with severe pancreatitis, characterized by multiple organ failure and
      pancreatic necrosis on CT scan (identified by an Acute Physiology and Chronic
      Health Evaluation II score of > or = 10 with > or = 3 Ranson criteria), most
      likely require aggressive nutritional support. Use of the enteral route of
      feeding may help contain the hypermetabolic stress response, reduce morphologic
      change and atrophy of the gut, and theoretically decrease late complications of
      nosocomial infection and organ failure. Evidence that decreasing degrees of
      stimulation of the pancreas occur as the site of feeding descends in the
      gastrointestinal tract and evidence from perspective, randomized trials suggest
      that jejunal feeding appears at least as safe and well tolerated as total
      parenteral nutrition in acute pancreatitis.

PMID- 9650026
TI  - Nutritional issues in inflammatory bowel disease.
AB  - Malnutrition is a very common problem in patients with chronic inflammatory bowel
      diseases. This article discusses the incidence, causes, and clinical consequences
      of malnutrition in these patient groups. The role of nutritional support
      administered enterally or parenterally either as primary or adjunctive therapy is
      highlighted, based on past and more recent controlled studies. Additional
      attention is given to the roles of glutamine, short-chain fatty acids, fish oil,
      and alternative nutritional therapy.

PMID- 9650027
TI  - New clinical issues in celiac disease.
AB  - Celiac disease is a chronic disorder of gluten sensitivity associated with a
      spectrum of mucosal lesions termed preinfiltrative, infiltrative, hyperplastic,
      destructive, and atrophic. The symptoms are not related to the degree of mucosal
      pathology but to the extent of the mucosal lesion. Neoplasms constitute the major
      complication of celiac disease, and EATCL is the most common neoplasm in this
      category. There is evidence that a strict gluten-free diet is protective against
      the complications of celiac disease; hence it is important that even the
      subclinical forms be diagnosed early. Small bowel biopsy remains the gold
      standard for diagnosis of celiac disease; however, antibody tests are a useful
      adjunct in deciding whom to biopsy and for screening groups at high risk before
      initiating a lifelong gluten-free diet.

PMID- 9650028
TI  - Short bowel syndrome.
AB  - This article discusses the causes, prognosis, and management of short bowel
      syndrome. Attempts to enhance intestinal adaptation with trophic factors and
      surgical treatment options, including small bowel transplantation, are discussed.

PMID- 9650029
TI  - Home parenteral nutrition. 25 years later.
AB  - After 25 years, there is enough clinical outcome experience to determine
      appropriate use of home parenteral nutrition in different disease states and age
      groups. Information regarding how to avoid complications and how patients and
      families can find necessary psychosocial support is provided in this article.
      Currently, small bowel transplantation is not a safer choice, unless there is
      severe liver disease caused by home parenteral nutrition or lack of central
      intervenous access.

PMID- 9650030
TI  - Metabolic bone disease in gut diseases.
AB  - A wide spectrum of gastrointestinal illnesses impairs bone health and can result
      in bone pain, demineralization, and fracture. This article summarizes current
      knowledge of the skeletal pathology exhibited in patients with diseases of the
      liver, biliary tree, pancreas, and bowel. Mechanisms responsible for these
      syndromes and treatment options are discussed. This article enhances the
      practicing gastroenterologist's knowledge of the implications of gastrointestinal
      illness for bone.

PMID- 9650031
TI  - Adjustment disorder: a multisite study of its utilization and interventions in
      the consultation-liaison psychiatry setting.
AB  - The consultation-liaison (C-L) psychiatry services of seven university teaching
      hospitals in the United States, Canada, and Australia (the MICRO-CARES
      Consortium) used a common clinical database to examine 1039 consecutive
      referrals. A diagnosis of adjustment disorder (AD) was made in 125 patients
      (12.0%); as the sole diagnosis, in 81 (7.8%); and comorbidly with other Axis I
      and II diagnoses in 44 (4.2%). It had been considered as a rule-out diagnosis in
      a further 110 (10.6%). AD with depressed mood, anxious mood, or mixed emotions
      were the commonest subcategories used. AD was diagnosed comorbidly most
      frequently with personality disorder and organic mental disorder. Sixty-seven
      patients (6.4%) were assigned a V code diagnosis only. Patients with AD were
      referred significantly more often for problems of anxiety, coping, and
      depression; had less past psychiatric illness; and were rated as functioning
      better--all consistent with the construct of AD as a maladaptation to a
      psychosocial stressor. Interventions were similar to those for other Axis I and
      II diagnoses, in particular, the prescription of antidepressants. Patients with
      AD required a similar amount of clinical time and resident supervision. It is
      concluded that AD is an important and time-consuming diagnostic category in C-L
      psychiatry practice.

PMID- 9650032
TI  - Risks for oral health with the use of antidepressants.
AB  - In this article, attention is focused on oral pathology, particularly dental
      caries, caused by hyposalivation as a consequence of (long-term) use of
      antidepressants. Changes in clinical psychiatric practice and increasing numbers
      of prescriptions of antidepressants in primary care and specialty care settings
      have made awareness of this risk even more relevant than in the past. Normal
      physiology of salivary glands and changes in the secretion of saliva during use
      of antidepressants are described. Monitoring, prevention, and treatment of
      hyposalivation induced by antidepressants are encouraged as an adjunct in the
      clinical management of depression.

PMID- 9650033
TI  - DSM-IV hypochondriasis in primary care.
AB  - The object of this study was to assess the prevalence and correlates of the DSM
      IV diagnosis of hypochondriasis in a primary care setting. A large sample (N =
      1456) of primary care users was given a structured interview to make diagnoses of
      mood, anxiety, and somatoform disorders and estimate levels of disability. The
      prevalence of hypochondriasis (DSM-IV) was about 3%. Patients with this disorder
      had higher levels of medically unexplained symptoms (abridged somatization) and
      were more impaired in their physical functioning than patients without the
      disorder. Of the various psychopathologies examined, major depressive syndromes
      were the most frequent among patients with hypochondriasis. Interestingly, unlike
      somatization disorder, hypochondriasis was not related to any demographic factor.
      Hypochondriasis is a relatively rare condition in primary care that is largely
      separable from somatization disorder but seems closely intertwined with the more
      severe depressive syndromes.

PMID- 9650034
TI  - How C-L services can comply with new HCFA guidelines.
AB  - A psychiatric consultation report form was developed to efficiently and
      accurately meet the stringent Medicare documentation guidelines that go into
      effect July 8, 1998. This form was designed for use in academic institutions
      where the consultation team includes teaching physicians, psychiatric residents,
      and medical students. Medicare has strict requirements regarding who may document
      each element of the consultation for billing purposes. These requirements were
      taken into account in the design of this form. Two academic consultation-liaison
      psychiatric services piloted the form and conducted internal audits to evaluate
      its usefulness. The accuracy of billing improved twofold at one site because the
      form facilitated rapid completion of details requisite to justify CPT codes of
      complex assessments. This saved considerable time and effort over the previous
      methods used to determine an appropriate level of billing. Critical information
      was documented more frequently, thereby meeting the documentation requirements
      more consistently. Instructions for use, criticisms, and cautions are given.

PMID- 9650035
TI  - Recovery and relapse in geriatric depression after treatment with antidepressants
      and ECT in a medical-psychiatric population.
AB  - The objective of this naturalistic, longitudinal treatment outcome study was to
      determine relapse rates in geriatric depression following treatment with
      antidepressants and electroconvulsive therapy in a medical-psychiatric
      population. Thirty-nine elderly patients (average age 71 years) with unipolar
      major depression were treated with either antidepressants (AD) or, if resistant
      to AD treatment, ECT followed by maintenance antidepressants. Patients were
      monitored over 18 months, and relapse rates were closely determined using the
      Longitudinal Interval Follow-up Evaluation (LIFE) and the 21-item Hamilton
      Depression Rating Scale. Although 90% of patients recovered from their index
      episode of depression, relapse rates were approximately 29%. These results
      indicate that in spite of high chances of recovery from geriatric depression,
      intensive psychopharmacologic and psychotherapeutic strategies are needed to
      decrease relapse rates in geriatric depression.

PMID- 9650036
TI  - Referral patterns and recognition of depression among African-American and
      Caucasian patients.
AB  - A retrospective review of psychiatric consultations was conducted for African
      American and Caucasian patients for a 2-year period. Reasons for referral,
      assigned diagnoses, accuracy rates, and discordance and concordance rates were
      assessed. Referrals for depression comprised 24.6% of all consults for Caucasian
      and African-American inpatients. Only 40.3% of patients referred for depression
      were diagnosed with a depressive disorder; 54.4% of patients diagnosed with
      depressive disorders were referred for other reasons. African-American patients
      were referred for evaluation of depression and diagnosed with depressive
      disorders significantly less often than Caucasian patients. No significant
      differences were obtained between African-Americans and Caucasians in the
      accuracy rates of patients referred for depression. Discordance and concordance
      rates for the two groups were comparable. Diagnoses assigned to African-Americans
      and Caucasians incorrectly referred for depression did not differ significantly.
      For depressed African-Americans and Caucasians referred for reasons other than
      depression, the only difference noted was in the referral rates for adjustment of
      psychotropics. The nonpsychiatric staff fails to recognize depression and often
      refer depressed patients inappropriately. Depressed patients are primarily
      referred for suicide assessment and disruptive behaviors. Referrals for
      depression may be a secondary concern to nonpsychiatric staff. In addition,
      cultural variables and racial differences between hospital staff and patients may
      account for the differences in referral patterns. Awareness of the needs of
      African-American patients is required.

PMID- 9650037
TI  - The contribution of cognitive impairment, medical burden, and psychopathology to
      the functional status of geriatric psychiatric inpatients.
AB  - In order to define the contributions of cognitive impairment, medical burden, and
      psychopathology to the functional status of geriatric psychiatric patients, a
      forward-looking, retrospective study of 106 consecutive admissions to a geriatric
      psychiatric unit at the Houston Veterans Affairs Medical Center Hospital was
      done. It was found that psychopathology and cognitive status, but not medical
      burden, contributed to the variance in functional status of geriatric psychiatric
      inpatients for both admission scores and for changes in scores during
      hospitalization. Improvements in cognitive state and psychopathology were
      associated with improvements in functional status during hospitalization.

PMID- 9650038
TI  - Psychotherapy with a woman at high risk for developing breast cancer.
AB  - Women who are at high risk for developing breast cancer increasingly consult with
      psychiatrists about the psychological, social, and sexual consequences of genetic
      testing and risk-reducing surgeries such as bilateral mastectomy and
      oophorectomy. The 9-year psychotherapy with a woman who had bilateral mastectomy
      because of her family history of breast cancer and who later tested negative for
      BRCA1 is described and discussed.

PMID- 9650039
TI  - Psychiatric morbidity in a series of patients referred from a trauma service.
AB  - We studied the clinical characteristics of trauma patients referred to psychiatry
      to determine whether these patients differ from the total trauma population. A
      chart review of trauma cases referred to psychiatry at our setting in 1995 (N =
      60) was compared with all 609 trauma admissions from the same period. The most
      common reasons for referral were suicide attempts and depression. The most common
      diagnosis was mood disorders (28%). The patients required an average 5.1 follow
      up visits. The psychiatric referral group had twice the length of stay.
      Psychiatric illness is relatively common in trauma patients and impacts on
      psychiatric service resources and length of hospital stay.

PMID- 9650040
TI  - Isolated systolic hypertension in the elderly--what's next?

PMID- 9650041
TI  - Is the decline in renal function with normal aging inevitable?
AB  - The structural changes observed in the normal aging kidney support a concept that
      one should expect a decline in renal function as one ages. Reports by renal
      physiologists, however, suggest that this is not always true. The suggestion is
      made that vascular adaptations to structural changes may help to preserve
      glomerular filtration rate by producing a state of hyperperfusion and
      hyperfiltration in surviving nephrons.

PMID- 9650042
TI  - The controversy surrounding cholesterol treatment in older people.
AB  - The evidence of the benefit of lowering cholesterol levels in seniors from
      epidemiologic studies and RCTs is conflicting. Epidemiologic studies suggest that
      elevated cholesterol levels in elderly people may be a marker of good health. In
      some cases, lowering cholesterol in seniors may even prove harmful. Conversely,
      RCTs of lipid-lowering therapy have shown clear benefits in reducing coronary
      events in younger and middle-aged adults with or without pre-existing CAD. Both
      the epidemiologic studies and the RCTs we evaluated have methodologic concerns
      that make generalization to all seniors difficult. One epidemiologic study, in
      fact, found that there may be a physiologic decline in cholesterol levels as
      people age into their 70s and beyond [16]. We still do not appear to have a clear
      insight into the precise role cholesterol plays in seniors, especially those over
      the age of 75. In the future, as more data becomes available from RCTs and meta
      analyses evaluating seniors in the older age group [15], we hope to have a better
      understanding of how to treat hypercholesterolaemia in this population. Until
      further studies are published, treatment plans need to be individualized, and the
      risks and benefits of treatment on various outcomes must be weighed according to
      the best evidence we have available.

PMID- 9650043
TI  - The treatment choice of elderly patients with erectile dysfunction.
AB  - The aim of this study was to determine treatment preference, commitment to choice
      of therapy, and the influence of physical disability on treatment choice in a
      geriatric group of males with erectile dysfunction (E.D.) of various etiologies.
      Eighty-nine patients aged 65 to 83 years (mean 69.5 years) were assessed and
      followed at our erectile dysfunction clinic from July 1991 to September 1996.
      Etiology of ED was based on clinical assessment. Available treatment options
      included oral medications, vacuum devices, injection therapy, penile prostheses,
      sex counseling and testosterone when indicated. Median follow-up since initial
      consultation was 9 months (range 1 to 63 months). Data was retrieved in a
      retrospective fashion from chart review and selective telephone follow-up.
      Clinical assessment yielded the following distribution of etiologies:
      vasculogenic (57.2%), neurogenic (7.9%), hormonal (1.1%), psychogenic (2.2%), and
      multifactorial (32.6%). The most popular initial treatment choices were injection
      therapy (30.3%), vacuum device (27.0%), and oral medication (20.2%). Of the 84
      patients who chose to be treated, 34 (40.5%) elected to switch to a different
      form of therapy after a median time of 7.5 months (range 1 week to 63 months).
      Five patients tried a third form of therapy and two proceeded to a fourth. The
      remaining patients have continued with their original choice for a median time of
      7 months (range 1 to 63 months). A greater drop-out rate (78%) amongst those who
      initially chose oral medication was statistically significant when compared to
      drop-out rates for injection therapy (48%) and vacuum devices (29%), p = 0.044
      and p = 0.005, respectively. Significant physical disabilities in eight patients
      did not appear to influence their treatment selection. In conclusion, the elderly
      are a unique group of patients who are more likely to have an organic etiology to
      their erectile dysfunction. When they do present with erectile dysfunction, they
      are inclined to pursue treatment. The choices made by this group of men did not
      differ from impotent men in general. When unsatisfied with one form of therapy
      they were inclined to pursue an alternative treatment. A significant physical
      disability did not preclude a therapeutic choice.

PMID- 9650045
TI  - Frequency urgency syndrome following urinary bladder suspension.
AB  - Bladder suspension for urinary incontinence secondary to bladder neck
      hypermobility is highly successful. Of those who fail, however, a subset will
      develop new onset or markedly worsened irritative voiding symptoms. A series of
      such patients were identified to study the associated urodynamic abnormalities of
      this symptom complex. The charts of female patients presenting for incontinence
      from 1992-94 were reviewed. Forty-six patients with a mean age of 59.4 (range 28
      79) fulfilled the inclusion criteria of developing new onset or markedly worsened
      post-operative frequency, urgency and urge incontinence within two years of
      undergoing bladder suspension. All had been evaluated with thorough history,
      physical examination, and urodynamic testing. Seventeen patients were found to
      have recurrent hypermobility. Eighteen had a diagnosis of intrinsic sphincter
      deficiency (ISD), including six that also had another diagnosis. Four patients
      were diagnosed with detrusor overactivity and seven with other miscellaneous
      diagnoses. Patients presenting with this symptom complex should be evaluated so
      that treatment can be tailored appropriately.

PMID- 9650044
TI  - Complications of vascular access in hemodialysis (HD)--aged vs adult patients.
AB  - Reports on the success of permanent vascular access in elderly HD patients vary
      considerably. We reviewed the records of 149 patients [62F and 87M] aged 20-89
      years old (median 59) who were on hemodialysis for 6-242 (49 median) months, and
      had undergone 202 vascular access procedures (177 Cimmino-Brescia fistulae and 25
      PTFE grafts). Patients were divided into two groups according to the age they
      started HD. Group A: 48 patients, over 60 years old (range 60-83; median 70) on
      HD for 43.5, (6-140) months. Group B: 101 patients, under 60 years old, range (15
      59) median 46, on HD for 54 (6-242) months. There were no differences between the
      two groups in terms of gender, primary renal disease, (except polycystic kidney
      disease), Hct and EPO administration. The initial choice of vascular access, the
      complications and the technique survival were examined in both groups. Cimmino
      Brescia fistulae were used as the first choice of vascular access in all patients
      except one in group B. PTFE-grafts were the second or third choice in 7/48 (group
      A) and 15/101 (group B) (p: NS). The only reason for technique failure was
      vascular thrombosis in both groups (11/48 group A and 31/101 group B p: NS).
      Other complications were: aneurysms (10/48 and 14/101, p: NS), infections (0/48
      and 2/101 p: NS) and edema (0/48 and 6/101, p: NS). Five-year technique survival
      of the first AV fistula in the two groups was 35% and 45% respectively (log-rank
      test, p: NS). These findings suggest that: a) A.V. fistula is the first choice of
      vascular access in aged HD patients; b) There is no difference in vascular access
      complications across age groups; c) Survival of the first A.V. fistula is
      independent of age.

PMID- 9650046
TI  - Nephrologic complications of drug therapy in the elderly.

PMID- 9650047
TI  - Acute renal failure in an elderly patient.

PMID- 9650048
TI  - Refractory severe nocturia: its treatment with intranasal desmopressin.

PMID- 9650049
TI  - Novel vaccines against Theileria parva: prospects for sustainability.
AB  - A first-generation subunit vaccine for East Coast fever based on the Theileria
      parva p67 sporozoite surface antigen is entering preliminary field trials.
      Intensive efforts are also focused on the identification of a schizont-specific
      component for incorporation in a second-generation multi-component product. It is
      clear that many questions remain unanswered regarding the likely performance of
      these vaccines under field conditions. In particular, their effect on the endemic
      status of the parasite in targeted areas will be crucial to their sustainability.
      Ideally, challenge should be maintained so that immunity is boosted in the
      absence of repeat vaccination. In the event that efficacy of the p67 vaccine in
      the field reflects that observed in extensive laboratory trials, it is possible
      that some reduction in the heterogeneity of the indigenous parasite population
      will occur, and this may be accompanied by selection for more highly infective
      strains. In contrast, available information suggests that schizont-specific
      components of a second-generation subunit vaccine are unlikely to affect the
      endemic status of parasite populations. However, endemic stability will
      inevitably decline as management systems become more intensive and necessitate
      frequent vaccination to maintain protective cover.

PMID- 9650050
TI  - Binding of [3H]m-aminolevamisole to receptors in levamisole-susceptible and 
      resistant Haemonchus contortus.
AB  - M-aminolevamisole, a potent analogue of the commercial anthelmintic levamisole,
      was used to investigate ligand-binding properties of homogenates of larval and
      parasitic stages of the nematode parasite of sheep, Haemonchus contortus.
      Kinetics of the binding of [3H]m-aminolevamisole to homogenates was measured in a
      drug-susceptible isolate and compared with a levamisole-resistant isolate.
      Equilibrium binding studies and kinetic studies revealed a high affinity binding
      component with a KD of 3 nM. A low affinity component (KD = 2.4 microM) was also
      apparent in equilibrium studies. High affinity [3H]m-aminolevamisole binding was
      displaced in a concentration-dependent manner by levamisole analogues and
      cholinergic agonists. Compared with the susceptible isolate, binding in a
      levamisole-resistant isolate of the parasite, was quantitatively similar over a
      range of developmental stages and binding conditions. However, under the
      conditions of binding there was a reduced affinity (larger KD) and more binding
      sites (larger Bmax) at the low affinity site in the resistant compared with the
      susceptible isolate. It was concluded that the ligand was binding to
      acetylcholine receptor populations of the nematode and that resistance may be
      associated with alterations in the low affinity site of this receptor.

PMID- 9650051
TI  - Determinants of transmission success of individual clones from mixed-clone
      infections of the rodent malaria parasite, Plasmodium chabaudi.
AB  - Interactions between malaria parasite clones within mixed infections can have a
      profound effect on transmission and therefore the epidemiology of the disease.
      However, factors which determine the relative transmission success of individual
      clones from mixed infections are unknown. We have used two clones of the rodent
      malaria Plasmodium chabaudi to investigate changes in the clonal composition of
      asexual parasites over the course of mixed-clone infections in mice and how these
      relate to the clonal composition of transmission (oocyst) populations in
      mosquitoes. Clonal composition was determined using monoclonal antibody analyses
      for the asexual blood stage populations and PCR analysis of single oocysts for
      the transmission populations in mosquitoes. The relative frequency of the two
      clones changed dramatically during the course of the infection in mice, depending
      on their ratio in the inoculum. The clonal composition of parasites within
      mosquitoes most closely resembled that in the asexual infection at the time of
      transmission rather than that at any point earlier in the infection. These
      results provide no evidence that clones increase rates of gametocytogenesis in
      response to competitive suppression. Most likely, transmission success follows
      from asexual success in the later parts of the infection. The clone which
      dominated the earlier part of the infection, when most parasites are produced,
      did not necessarily dominate the transmission from the infection. The two clones
      differed in competitive ability and the data suggest that interactions with the
      host immune system may be a major factor in determining transmission success from
      mixed-clone infections.

PMID- 9650052
TI  - Parasite extinction and colonisation and the evolution of parasite communities: a
      simulation study.
AB  - We determined what evolutionary processes influence the likelihood of detecting
      an effect of host ecological characteristics on the richness of parasite
      communities in comparative analyses among related host species. We used a
      mathematical model to generate phylogenies of hosts in which parasite communities
      varied over evolutionary time as parasite species were either gained or lost
      during host speciation events. Gain or loss of parasites were stochastic and
      could either be strongly, moderately, weakly, or not, affected by host ecological
      characteristics. The model was evaluated over this range of effects of host
      ecology, and for various mean probabilities of parasite gain and loss and various
      rates of change in host ecological characteristics at speciation events. Our
      results suggest that phylogenetic effects (the passing of parasite species from
      mother to daughter host species) are likely to obscure ecological effects (the
      effect of host body size, diet, habitat, lifespan, etc.) except when the effects
      of host ecology are strong, and the probabilities of gain or loss of parasites
      are high, or host ecological characteristics change markedly at speciation
      events. This outcome was not influenced by the shape of the phylogenetic tree
      used in the simulations. Sensitivity analysis of our model also shows this result
      to be robust to a wide range of assumptions and parameter values. Thus, because
      the composition of parasite communities tends to reflect their ancestry, the
      effect of host ecology will often be very difficult to detect.

PMID- 9650053
TI  - Attempts to generate immunity against Trichostrongylus colubriformis and
      Haemonchus contortus in young lambs by vaccination with viable parasites.
AB  - The ability of young Merino lambs to achieve protective immunity following
      vaccination via viable nematode infections was assessed. Lambs were infected from
      1 month of age by repeated continuous low dose (trickle) administration of
      Trichostrongylus colubriformis or Haemonchus contortus infective larvae (L3), or
      by truncated infections with high doses of viable T. colubriformis L3. After 7
      weeks all groups were drenched with anthelmintic and at 3 months of age they were
      re-infected with the homologous species. Protection was assessed by faecal egg
      counts at 3, 4, 5, 6 and 7 weeks after challenge, and worm count at 7 weeks after
      challenge. Young lambs were partially protected by 3 months of age against
      Trichostrongylus by trickle infection. This protection correlated with local mast
      cell and T-cell priming, increased numbers of local antigen-presenting cells and
      T-cells and increased worm-specific antibody titres in the intestine. However,
      there was no evidence that young lambs were capable of immunologically
      recognising H. contortus antigens following trickle infection, nor did trickle
      infection significantly protect young lambs against Haemonchus challenge.

PMID- 9650054
TI  - The effects of parasites on a wild population of the Mountain Brushtail Possum
      (Trichosurus caninus) in south-eastern Australia.
AB  - The effects of a reduction of parasite burdens were determined in adult female
      Mountain Brushtail Possums, Trichosurus caninus, on the birth, mortality and
      growth rates of pouch-dependent young, as well as the haematological and serum
      biochemical values of the mothers. The efficacy of the anthelmintic drug
      ivermectin for reducing parasite burdens in this host was assessed using faecal
      and necropsy examinations of a small number of animals. Ivermectin began to
      reduce parasite burdens by 48 h after treatment. In the second stage of the
      experiment, animals were treated or sham injected (control individuals) with
      ivermectin and praziquantel at 8-10-week intervals throughout the breeding season
      to the time of emergence of young from the pouch. Treatment with ivermectin and
      praziquantel had no significant effect on the proportion of females giving birth,
      or on the survival of young to emergence. An effect of treatment was recorded for
      absolute eosinophil counts in adult females, which, in spring; were higher among
      control animals than those that were treated.

PMID- 9650055
TI  - A Taenia solium oncosphere protein homologous to host-protective Taenia ovis and
      Taenia saginata 18 kDa antigens.
AB  - A Taenia solium cDNA (TSOL-18) encoding a protein with close homology to host
      protective oncosphere antigens from Taenia ovis (To18) and Taenia saginata (TSA
      18) is described here. TSOL-18 was cloned from mRNA obtained from hatched and
      activated oncospheres of T. solium. The high level of predicted amino acid
      sequence homology among TSOL-18 and other host protective taeniid antigens
      suggests that the protein expressed by TSOL-18 may be capable of being used as a
      vaccine against T. solium infection in the parasite's intermediate hosts.

PMID- 9650056
TI  - Quantitative and qualitative changes in intestinal goblet cells during primary
      infection of Trichostrongylus colubriformis high and low responder guinea pigs.
AB  - Small intestine goblet cell numbers and the composition of their mucus were
      compared in guinea pigs with genetically determined differences in responsiveness
      to Trichostrongylus colubriformis infection. Prior to infection, no differences
      between high responder and low responder animals were detected. However,
      following primary infection with T. colubriformis, pronounced goblet cell
      hyperplasia developed and the proportion of sulphomucin in these cells increased.
      Both changes developed significantly earlier in high responder animals.

PMID- 9650057
TI  - Molecular phylogeny of the families Campulidae and Nasitrematidae (Trematoda)
      based on mtDNA sequence comparison.
AB  - Historically, the systematic arrangement of the genera within the family
      Campulidae, and its relationship with its allied family Nasitrematidae have been
      rather confused, particularly because only adult morphology has been available to
      classical taxonomic analysis. In this paper we provide a partial phylogeny of the
      genera of these families based on mtDNA from five campulid species: Campula
      oblonga, Zalophotrema atlanticum, Hadwenius tursionis, Oschmarinella rochebruni
      and Orthosplanchnus fraterculus; and one nasitrematid, Nasitrema globicephalae.
      Fasciola hepatica and Dicrocoelium dendriticum were used as outgroups. Maximum
      parsimony and neighbour-joining methods were applied. Both methods produced
      similar trees where H. tursionis appeared as the basal campulid, with a
      sequential divergence of Z. atlanticum, N. globicephalae, C. oblonga, O.
      rochebruni and O. fraterculus. Results suggest that Nasitrematidae as defined
      should loose its familial status and the current subfamilial division of the
      family Campulidae is at least partly artificial and should not be maintained.

PMID- 9650058
TI  - Triploid form of Fasciola in Japan: genetic relationships between Fasciola
      hepatica and Fasciola gigantica determined by ITS-2 sequence of nuclear rDNA.
AB  - The ITS-2 sequences from seven worms of the Japanese triploid form of Fasciola,
      two of Fasciola hepatica from Uruguay and four of Fasciola gigantica from Zambia
      and Indonesia were determined. The ITS-2 sequences of the Japanese triploid worms
      were divided into two distinct types, one of which was almost identical to that
      of F. hepatica and the other to F. gigantica from Indonesia.

PMID- 9650059
TI  - Evidence of multiple mechanisms of avermectin resistance in haemonchus contortus-
      comparison of selection protocols.
AB  - Three isolates of Haemonchus contortus selected for avermectin resistance in
      sheep were compared in three in vitro pharmacological tests previously shown to
      discriminate between field isolates of H. contortus resistant and susceptible to
      the avermectins. Two isolates, F7-A and IVC, were selected for avermectin
      resistance in the laboratory from a reference susceptible isolate using
      suboptimal doses of ivermectin (LD95) for 7 and 16 generations, respectively. In
      these isolates avermectin resistance was not associated with a decreased
      sensitivity to avermectin inhibition of larval development or L3 motility but was
      associated with an increased sensitivity to paraherquamide. The third isolate,
      Warren, was derived from an overwhelmingly avermectin-susceptible, mixed species
      field isolate in a single generation by propagating the small number of survivors
      of a 0.2 mg/kg ivermectin treatment (i.e. 10 x LD95). This isolate, like
      previously characterised avermectin-resistant H. contortus isolates derived from
      the field in South Africa and Australia, showed a markedly reduced sensitivity to
      avermectin inhibition of larval development and L3 motility, as well as an
      increased sensitivity to paraherquamide. These results suggest that avermectin
      resistance can manifest itself in different ways and that the two selection
      protocols used to generate the F7-A, IVC and Warren isolates have resulted in the
      selection of different resistance phenotypes.

PMID- 9650060
TI  - Effect of plant species on the larvae of gastrointestinal nematodes which
      parasitise sheep.
AB  - Faeces containing Trichostrongylus colubriformis and/or Ostertagia circumcincta
      eggs were used to provide four contaminations in each of 2 years on plots of
      browntop, Yorkshire fog, ryegrass, tall fescue, lucerne, chicory, cocksfoot,
      white clover, and prairie grass and in the second year a mixed sward of
      ryegrass/white clover. Third stage larvae were recovered from faeces and from
      four strata of herbage, 0-2.5, 2.5-5, 5-7.5 and > 7.5 cm above the soil surface
      at 2, 4, 6, 8, 11, and 14 weeks after faeces were deposited on the swards.
      Herbage species had a significant (P < 0.0001) effect on the number of larvae
      recovered. Greatest numbers of larvae, as indicated by ranking analysis, were
      recovered from Yorkshire fog, ryegrass, and cocksfoot and lowest numbers from
      white clover and lucerne. The difference between herbages in numbers of larvae
      recovered was due to the "development success", the ability of larvae to develop
      to the infective stage and migrate on to herbage, rather than "survival", the
      rate of population decline once on the herbage. Faecal degradation was most rapid
      from white clover and browntop, intermediate from tall fescue, lucerne, prairie
      grass, cocksfoot, and ryegrass, and slowest from Yorkshire fog swards. The
      numbers of larvae recovered from herbages were related (r2 = 0.59, P < 0.05) with
      the faecal mass remaining. A greater proportion of the total larvae recovered
      from the herbage was recovered from the bottom stratum of Yorkshire fog and
      prairie grass than from white clover, with the other herbages intermediate,
      indicating that larvae had greater difficulty migrating up Yorkshire fog and
      prairie grass than the other herbage species. In most herbage species, despite
      more larvae being recovered from the lowest stratum, larval density (L3/kg
      herbage DM) was highest in the top stratum. This study has demonstrated that
      herbage species can have a significant impact on the population dynamics and
      vertical migration of T. colubriformis and O. circumcincta larvae.

PMID- 9650061
TI  - The application of chaetotaxy in the discrimination of Gyrodactylus salaris
      Malmberg, 1957 (Gyrodactylidae: Monogenea) from species of the genus parasitising
      British salmonids.
AB  - The chaetotaxy of argentophilic structures on three species of the monogenean
      genus Gyrodactylus was investigated in an attempt to distinguish species of this
      genus. Maps were prepared for Gyrodactylus salaris from Scandinavia and compared
      with two native species of Gyrodactylus parasitising salmonids in Britain, namely
      Gyrodactylus derjavini and Gyrodactylus truttae. The maps were subsequently
      refined and analysed for zones of homology and differentiation. The results
      demonstrate that G. salaris can be readily distinguished by this technique, which
      is, therefore, of great potential value in the identification of this notifiable
      pathogen. The key aggregations of sensilla discriminating G. salaris are,
      ventrally, the antero-ventral set, the medio-lateral set and the postero-lateral
      set, and, dorsally, the postero-dorsal set.

PMID- 9650062
TI  - Association of host cell intermediate filaments with Toxoplasma gondii cysts in
      murine astrocytes in vitro.
AB  - Toxoplasma gondii is an intracellular parasite that is a common opportunistic
      infection of AIDS patients where it causes a severe and often fatal encephalitis.
      Toxoplasmic encephalitis in AIDS patients results from a reactivation of the cyst
      stage of Toxoplasma gondii in the brain. A previous study found an association of
      host cell intermediate filaments with parasitophorous vacuoles and some studies
      have suggested the host cell cytoskeletal elements are incorporated into the cyst
      wall. In this study, the interaction of glial filaments with Toxoplasma gondii
      cysts was studied in cysts derived in vitro in mouse astrocytes and in cysts
      isolated from mouse brains. Glial filaments, detected by immunostaining of the
      glial fibrillary acidic protein, were found to accumulate around the perimeter of
      the cysts as they developed in mouse astrocytes. Transmission electron microscopy
      revealed a layer of glial filaments was wrapped around the cytoplasmic side of
      the cyst. The glial filaments were present in close apposition to the cyst wall
      and arranged around the cysts in a concentric layer, measuring 5-10 microns in
      thickness. The layer of glial filaments excluded host cell mitochondria and
      endoplasmic reticulum from the cytoplasmic surface of the cyst. Colocalisation of
      glial fibrillary acidic protein and the cyst wall via confocal and immunoelectron
      microscopy, confirmed that there was no glial fibrillary acidic protein present
      within the cyst wall. The cyst wall of cysts isolated from mouse brains were also
      found to be negative for glial fibrillary acidic protein. In conclusion, we found
      no evidence of structural integration of the host cell intermediate filaments in
      the cyst wall, but glial filaments were found to encase the cysts in the host
      cell during cyst development in host cells in vitro. The glial filaments wrapping
      of cysts may play a role in bradyzoite differentiation and/or cyst stabilisation
      in the host cell cytoplasm.

PMID- 9650063
TI  - Immunocytochemical detection of vasoactive intestinal peptide-like and peptide
      histidine isoleucine-like peptides in the nervous system and the excretory system
      of adult Nippostrongylus brasiliensis.
AB  - Vasoactive intestinal peptide-like and peptide histidine isoleucine-like
      immunoreactivities were detected in the excretory duct of adult male and female
      Nippostrongylus brasiliensis, thus indicating the source of these two
      physiologically active peptides previously isolated from the excretory/secretory
      products of adult N. brasiliensis. In the nervous system immunoreactivity to both
      these peptides was confined to females and was found in the neurons of the
      ovijector associated ganglion. This is consistent with co-synthesis of vasoactive
      intestinal peptide-like and peptide histidine isoleucine-like peptides which has
      also been shown to occur in all mammalian vasoactive intestinal peptid-ergic
      neurons studied to date. However, in addition to this, and in common to some
      previous studies on helminth vasoactive intestinal peptide and peptide histidine
      isoleucine immunoreactivities, co-synthesis of the peptides was not indicated in
      a pair of branched neurons which projected posteriorly and peripherally from the
      ganglion associated with the ovijector of females and which terminated in two
      pairs of ganglia also exhibiting vasoactive intestinal peptide-like
      immunoreactivity only. The position of these ganglia indicated that they
      innervate muscles close to the body wall and may be responsible for the muscular
      contractions required for expulsion of eggs from female Nippostrongylus
      brasiliensis. This is also the first study to successfully detect these peptides
      in the excretory system of gastrointestinal nematodes.

PMID- 9650064
TI  - Comparative sequence analysis of the intergenic spacer region of cyathostome
      species.
AB  - The ribosomal DNA intergenic spacer was amplified by the polymerase chain
      reaction from 16 cyathostome species using primers derived from conserved regions
      within the flanking 18S and 26S rRNA genes. This generated a 1.5-2.5 kb fragment
      which was sequenced from five species. The areas covering the 26S and 18S rRNA
      genes were more than 99% similar among the five species. Furthermore, in all
      species there existed a highly conserved region of approximately 380 bp at the 3'
      end of the intergenic spacer. Subsequently, two cyathostome-specific primers were
      designed to amplify a smaller, more variable region of the intergenic spacer.
      Eleven further species were amplified using these primers and analysis showed
      that sequence similarities varied from 40 to 97% between species. The sequence
      information obtained in this study is being used to develop a PCR-based assay for
      the differentiation of preparasitic stages of cyathostomes.

PMID- 9650065
TI  - Grandparental impact in young adults' relationships with their closest
      grandparents: the role of relationship strength and emotional closeness.
AB  - This study explored the role that relationship strength, generally, and emotional
      closeness, more specifically, may play in delimiting the bounds of grandparental
      influence in young adults' lives. One-hundred and seventy-one college-aged young
      adults completed a questionnaire evaluating their relationship with the living
      grandparent to whom they felt most emotionally close or, if they felt close to
      none of their living grandparents, the grandparent with whom they had the most
      contact. Participants' perceptions of the strength of this relationship were
      significantly and positively related to their responses on measures of the extent
      to which their closest grandparent influenced various aspects of their lives
      (e.g., their beliefs and values, how much their lives would be missing had they
      never known the grandparent). In addition, participants whose grandparent
      grandchild relationships were emotionally close endorsed a broader range of
      alternatives on checklist measures of perceived relationship impact than did
      those whose relationships were more emotionally distant.

PMID- 9650066
TI  - (Re)constructing relationships with grandparents: a turning point analysis of
      granddaughters' relational development with maternal grandmothers.
AB  - This study explores how granddaughters account for the development of their
      relationships with their maternal grandmothers. The retrospective interviewing
      technique was used to elicit turning points in their relational histories.
      Analysis of the turning point content revealed several different types of turning
      points that reflected both normative and idiosyncratic events. Increases in
      relational closeness resulted from decreases in geographic separation, engaging
      in shared activities, deaths or serious illnesses in the family, and family
      disruptions. Decreases in closeness were associated with negative experiences
      with the grandmother, increases in geographic separation, and the transition to
      college. Granddaughters reported that turning points related to death or serious
      illness and participation in shared activities were the most significant ones in
      their relationships with maternal grandmothers.

PMID- 9650067
TI  - Coping with the stress of immigration among new immigrants to Israel from
      Commonwealth of Independent States (CIS) who were exposed to Chernobyl: the
      effect of age.
AB  - This study examined the differential effect of age on coping and psychological
      measures among immigrants from Commonwealth of Independent States (CIS) to
      Israel. Some of these immigrants originated in the Republics adjacent to the
      Chernobyl Power Plant, site of the 1986 accident. The sample consisted of 708
      immigrants who were interviewed between the years 1993-1995 with an average age
      of 47.5 (sd 11.8). This sample was reinterviewed approximately a year and three
      months later (n = 520). The sample included two exposure groups--high exposed and
      low exposed based on the estimated levels of ground cesium contamination from the
      IAEA maps and a comparison group matched by age, gender, and year of immigration.
      Those over the age of sixty-five were disadvantaged, compared to those aged fifty
      to sixty-four, and younger, when it came to the tasks of immigrant absorption;
      learning the language, working and acquiring an income, and establishing
      alternative social networks which could offer support in times of illness. The
      psychological variables showed that over time, somatization, depression, and post
      traumatic stress disorder (PTSD) symptoms related to Chernobyl improved, however
      at a much slower pace for older immigrants (aged 55 and over) compared to younger
      ones.

PMID- 9650068
TI  - Measurement of aging anxiety in an elderly Australian population.
AB  - The purpose of this investigation was to modify an existing aging anxiety scale
      to produce an instrument specifically designed to assess aging anxiety in an
      elderly population. Existing instruments fail to consistently orientate aging
      associated threats into the future, and this poses a significant problem for the
      measurement of aging anxiety in the elderly population. It is proposed that this
      factor has confounded reports of the relationship between aging anxiety and
      advancing age. An existing valid and reliable instrument, the Anxiety about Aging
      Scale was modified for use with elderly respondents and tested on 123 independent
      community dwelling elderly individuals. The results indicated the modified scale
      provides a valid assessment of aging anxiety in the elderly.

PMID- 9650069
TI  - The association between mortality, morbidity and age in New Zealand's oldest old.
AB  - People aged eighty-five years and over (the oldest old) will form an increasing
      proportion of the population of New Zealand and many other countries. Because of
      their smaller numbers and relative inaccessibility, their health status has
      sometimes been extrapolated from populations of people aged sixty-five to eighty
      four years. For people aged sixty-five to eighty-four years an exponential
      relationship is seen between age and morbidity and mortality. We explore if this
      exponential relationship extends to people aged ninety years and over. We
      analyzed data from the New Zealand 1991 Census and 1992 hospital discharge
      records and, for people aged sixty to eighty-nine years, confirmed an exponential
      relationship between age and mortality, inactivity, hospital utilization, and
      occupation of residential institutions. This exponential trend did not continue
      for people aged ninety years and over for whom mortality rates and indicators of
      morbidity were considerably lower than expected, and conclude that the actual
      health status of people aged ninety years and over is better than the status
      extrapolated from that of people aged sixty to eighty-nine years.

PMID- 9650070
TI  - Genealogy of the alpha-crystallin--small heat-shock protein superfamily.
AB  - Sequences of 40 very diverse representatives of the alpha-crystallin-small heat
      shock protein (alpha-Hsp) superfamily are compared. Their characteristic C
      terminal 'alpha-crystallin domain' of 80-100 residues contains short consensus
      sequences that are highly conserved from prokaryotes to eukaryotes. There are, in
      addition, some positions that clearly distinguish animal from non-animal alpha
      Hsps. The alpha-crystallin domain is predicted to consist of two hydrophobic beta
      sheet motifs, separated by a hydrophilic region which is variable in length.
      Combination of a conserved alpha-crystallin domain with a variable N-terminal
      domain and C-terminal extension probably modulates the properties of the various
      alpha-Hsps as stress-protective and structural oligomeric proteins. Phylogeny
      reconstruction indicates that multiple alpha-Hsps were already present in the
      last common ancestor of pro- and eukaryotes. It is suggested that during
      eukaryote evolution, animal and non-animal alpha-Hsps originated from different
      ancestral gene copies. Repeated gene duplications gave rise to the multiple alpha
      Hsps present in most organisms.

PMID- 9650071
TI  - The effect of the intersubunit disulfide bond on the structural and functional
      properties of the small heat shock protein Hsp25.
AB  - The murine small heat shock protein Hsp25 carries a single cysteine residue in
      position 141 of its amino acid sequence. Interestingly, Hsp25 can exist within
      the cell as covalently bound dimer which is linked by an intermolecular disulfide
      bond between two monomers. Oxidative stress caused by treatment of the cells with
      diamide, arsenite, or hydrogen peroxide leads to an increase in Hsp25
      dimerisation which can be blocked by simultaneous treatment with reducing agents.
      Recombinant Hsp25 was prepared in an oxidized dimeric (oxHsp25) and reduced
      monomeric (redHsp25) from. The two species were compared with regard to secondary
      structure, stability, oligomerization properties and their chaperone activity. It
      is demonstrated by CD measurements in the far UV region that there are no
      significant differences in the secondary structure and temperature- or pH
      stability of oxHsp25 and redHsp25. However, according to CD measurements in the
      near UV region an increase in the asymmetry of the microenvironment of aromatic
      residues in oxHsp25 is observed. Furthermore, an increase in stability of the
      hydrophobic environment of the tryptophan residues mainly located in the N
      terminal domain of the protein against urea denaturation is detected in oxHsp25.
      Both reduced and oxidized Hsp25 from oligomeric complexes of similar size and
      stability against detergents and both species prevent thermal aggregation of
      citrate synthase and assist significantly in oxaloacetic acid-induced refolding
      of the enzyme. Hence, the overall secondary structure, the degree of
      oligomerization and the chaperone activity of Hsp25 seem independent of the
      formation of the intermolecular disulfide bond and only the stability of the
      hydrophobic N-terminal part of the molecule is influenced by formation of this
      bound. The obtained data do not exclude the possible involvement of dimerization
      of this protein in other cellular functions, e.g. in intracellular sulfhydryl
      buffering or in the protection of actin filaments from fragmentation upon
      oxidative stress.

PMID- 9650072
TI  - Refinement of 3D structure of bovine lens alpha A-crystallin.
AB  - In absence of 3D structures for alpha-crystallin subunits, alpha A and alpha B,
      we utilized a number of experimental and molecular modeling techniques to
      generate working 3D models of these polypeptides (Farnsworth et al., 1994. In
      Molecular Modeling: From Virtual Tools to Real Problems (Eds. Kumosinski, T.F.
      and Liebman, M.N.) ACS Symposium Series 576, Ch. 9:123-134, 1994, ACS Books,
      Washington DC). The refinement of the initial bovine alpha A model was achieved
      using a more accurate estimation of secondary structure by new/updated methods
      for analyzing the far UV-CD spectra and by neural network secondary structure
      predictions in combination with database searches. The spectroscopic study
      reveals that alpha-crystallin is not an all beta-sheet protein but contains
      approximately 17% alpha-helices, approximately 33% beta-structures and
      approximately 50% turns and coils. The refinement of the alpha A structure
      results in an elongate, asymmetric amphipathic molecule. The hydrophobic N
      terminal domain imparts the driving force for subunit aggregation while the more
      flexible, polar C-terminal domain imparts aggregate solubility. In our quaternary
      structure of the aggregate, the monomer is the minimal cooperative subunit. In
      bovine alpha A, the highly negatively charged C-terminal domain has three small
      positive areas which may participate in dimer or tetramer formation of
      independently expressed C-terminal domains. The electrostatic potential of
      positive areas is modulated and become more negative with phosphorylation and ATP
      binding. The refined bovine alpha A model was used to construct alpha A models
      for the human, chick and dogfish shark. A high degree of conservation of the
      three dimensional structure and the electrostatic potential was observed. Our
      proposed open micellar quaternary structure correlates well with experimental
      data accumulated over the past several decades. The structure is also predictive
      of the more recent data.

PMID- 9650073
TI  - Mutations and modifications support a 'pitted-flexiball' model for alpha
      crystallin.
AB  - alpha-Crystallin is renown for resisting crystallization and electron microscopic
      image analysis. The spatial conformation thus remaining elusive, the authors
      explored the structure and chaperone functioning by analyzing the effects of site
      directed mutagenesis, the properties of naturally occurring aberrant forms of
      alpha-crystallin and the influence of chemical modifications. The authors
      observed that the globular multimeric structure, as well as the chaperoning
      capacity are remarkably tolerant towards changes and modifications in the primary
      structure. The essential features of the quaternary structure--globular shape,
      flexibility, highly polar exterior and accessible hydrophobic surface pockets-
      support a 'pitted-flexiball' model, which combines tetrameric subunit building
      blocks in an open micelle-like arrangement.

PMID- 9650074
TI  - NMR spectroscopy of alpha-crystallin. Insights into the structure, interactions
      and chaperone action of small heat-shock proteins.
AB  - The subunit molecular mass of alpha-crystallin, like many small heat-shock
      proteins (sHsps), is around 20 kDa although the protein exists as a large
      aggregate of average mass around 800 kDa. Despite this large size, a well
      resolved 1H NMR spectrum is observed for alpha-crystallin which arises from
      short, polar, highly-flexible and solvent-exposed C-terminal extensions in each
      of the subunits, alpha A- and alpha B-crystallin. These extensions are not
      involved in interactions with other proteins (e.g. beta- and gamma-crystallins)
      under non-chaperone conditions. As determined by NMR studies on mutants of alpha
      A-crystallin with alterations in its C-terminal extension, the extensions have an
      important role in acting as solubilising agents for the relatively-hydrophobic
      alpha-crystallin molecule and the high-molecular-weight (HMW) complex that forms
      during the chaperone action. The related sHsp, Hsp25, also exhibits a flexible C
      terminal extension. Under chaperone conditions, and in the HMW complex isolated
      from old lenses, the C-terminal extension of the alpha A-crystallin subunit
      maintains its flexibility whereas the alpha B-crystallin subunit loses, at least
      partially, its flexibility, implying that it is involved in interaction with the
      'substrate' protein. The conformation of 'substrate' proteins when they interact
      with alpha-crystallin has been probed by 1H NMR spectroscopy and it is concluded
      that alpha-crystallin interacts with 'substrate' proteins that are in a
      disordered molten globule state, but only when this state is on its way to large
      scale aggregation and precipitation. By monitoring the 1H and 31P NMR spectra of
      alpha-crystallin in the presence of increasing concentrations of urea, it is
      proposed that alpha-crystallin adopts a two-domain structure with the larger C
      terminal domain unfolding first in the presence of denaturant. All these data
      have been combined into a model for the quaternary structure of alpha-crystallin.
      The model has two layers each of approximately 40 subunits arranged in an annulus
      or toroid. A large central cavity is present whose entrance is ringed by the
      flexible C-terminal extensions. A large hydrophobic region in the aggregate is
      exposed to solution and is available for interaction with 'substrate' proteins
      during the chaperone action.

PMID- 9650075
TI  - alpha-Crystallin quaternary structure and interactive properties control eye lens
      transparency.
AB  - The eye lens is the foremost biological system where function is directly under
      control of the physico-chemical properties of the cytoplasmic macromolecular
      solution. Indeed, lens transparency and opacity, lens refractive index gradient
      and viscosity, are the result of the structural and interactive properties of the
      crystallins, of their stability, of the fine tuning of their interaction
      potentials and associations at different levels of organization. Among the
      different crystallin classes, alpha-crystallins have represented a major
      challenge for a long time. The alpha-crystallin secondary, tertiary and
      quaternary structures are still unknown. On the functional side, however, it is
      established that alpha-crystallin quaternary structure and repulsive interactions
      determine lens transparency, whereas the alpha-crystallin chaperone effect most
      probably plays a role in the aging process. In the present paper, we recall the
      physico-chemical properties and the quaternary structure features of alpha
      crystallins that were demonstrated to control light scattering and transparency.
      The interest of a crystallin mixture for lens function is discussed. Then, a
      formal approach is proposed to design models for the alpha-crystallin quaternary
      structure, including the question of whether alpha-crystallins assemble with
      symmetry. An hypothesis relevant to the fold of the alpha-crystallin C-terminal
      domain is presented in another paper in this issue.

PMID- 9650076
TI  - alpha-Crystallin C-terminal domain: on the track of an Ig fold.
AB  - New results obtained from a two-dimensional sequence analysis of the small heat
      shock protein (shsp) family are described. It is confirmed that the conserved C
      terminal alpha-crystallin domain is essentially made of beta-strands, most
      probably two groups of beta-strands separated by a large loop. A direct
      correspondence between the putative beta-strands that have been identified in
      shsps and the seven beta-strands of a classical immunoglobulin-like fold is
      proposed. The hypothesis that the shsp family could belong to the immunoglobulin
      superfamily (IgSF) is consistent with the ubiquitous distribution and the
      multifunctional properties of the crystallins that are now emerging.

PMID- 9650077
TI  - Quaternary structure of bovine alpha-crystallin: influence of temperature.
AB  - The tertiary and quaternary structure of alpha-crystallin is still a matter of
      controversy. We have characterized the native alpha-crystallin quaternary
      structure by isolating it at the in vivo temperature and solvent conditions. It
      can be represented by a distribution of expanded particles with a weight average
      molar mass of 550,000 g/mol. On decreasing (to 4 degrees C) or increasing (up to
      50 degrees C) the temperature, the size distribution increases to larger
      particles. Only at lower temperatures (4 degrees C), a stable population of
      particles is obtained with weight average molar mass of 700,000 g/mol. In all
      conditions, alpha-crystallin behaves as a very expanded particle with a maximum
      hydrodynamic volume of 3.15 ml/g. The transitions in quaternary structure are
      rather slow: it takes several hours to evolve from a population of aggregates,
      characteristic for given solvent conditions, to another distribution in size and
      quaternary structure on changing the environment. The quaternary structure of
      alpha-crystallin is an uncharacteristic parameter of the particle: a broad
      distribution of values can be obtained on changing the environment. Any realistic
      model should include this property. Our studies favor an open loose structure,
      where peptides can be added or removed without drastic changes of secondary and
      tertiary structure of the peptides.

PMID- 9650078
TI  - Hydrophobicity and flexibility of alpha A- and alpha B-crystallin are different.
AB  - Since the discovery that the lens protein alpha-crystallin is also found in non
      lenticular tissues and can function as a chaperone, relatively little attention
      has been paid to differences in properties between alpha A- and alpha B
      crystallin, which form mixed aggregates in the lens but have so far never been
      found together in other tissues. In this study hydrophobicity and flexibility,
      properties that are thought to be relevant for chaperone function, are compared
      for alpha A- and alpha B-crystallin. Hydrophobicity was monitored from sodium
      dodecylsulphate polyacrylamide gel electrophoresis in the absence and presence of
      (methyl-substituted) ureas. Flexibilities were calculated from primary
      structures. Based on literature data also some other properties are compared. The
      results indicate significant difference in hydrophobicity profile, flexibility of
      the terminal parts and stability of alpha A- and alpha B-crystallin.

PMID- 9650079
TI  - Thermodynamic stability of bovine alpha-crystallin in its interactions with other
      bovine crystallins.
AB  - Light scattering measurements were performed on dilute solutions of alpha
      crystallin mixed with different combinations of beta H, beta L and gamma
      fractions of bovine lens crystallins. Light scattering intensities were obtained
      as a function of scattering angle, concentration and temperature. The temperature
      dependence of the second virial coefficients was used to obtain partial molar
      enthalpy and end entropy of solutions. The difference between the thermodynamic
      parameters of the crystallin mixtures and those of the weighted averages of the
      individual components yielded the excess enthalpy and entropy functions of the
      solutions. Both the excess enthalpy and entropy functions indicated that
      thermodynamic stability of alpha-crystallin is progressively enhanced by its
      interactions with gamma [symbol: see text] (beta H + gamma) [symbol: see text]
      (beta H + beta L + gamma) crystallins. The last two combinations showed negative
      values both for excess enthalpy as well for excess entropy of solutions. Other
      combinations demonstrated increasing positive values. This implies that the
      combination of all four crystallins in the vertebrate lens enables the best
      solvation property as well as the best packing as opposed to any other single or
      combinatorial arrangements of crystallins. Similar conclusions have been obtained
      in the past from water and other vapor sorption studies.

PMID- 9650080
TI  - alpha-Crystallin polymers and polymerization: the view from down under.
AB  - Several models have been proposed for the quaternary structure of alpha
      crystallin. Some suggest the subunits are arranged in concentric shells. Others
      propose that the subunits are in a micelle-like arrangement. However, none is
      able to satisfactorily account for all observations on the protein and the
      quaternary structure of alpha-crystallin remains to be established. In this
      review, factors contributing to the assembly and polymerization are examined in
      order to evaluate the different models. Consideration of the variations in
      particle size and molecular weight under different conditions leads to the
      conclusion that alpha-crystallin cannot be a micelle or a layered structure.
      Instead, it is suggested that the protein may be assembled from a 'monomeric'
      unit comprising eight subunits arranged in two tetramers with cyclic symmetry.
      The octameric unit is proposed to be disc-like particle with a diameter of 9.5 nm
      and a height of 3 nm. The larger particles, chains and sheet-like structures
      commonly observed are assembled from the octamers. Structural predictions
      indicate that the polypeptide may be folded into three independent domains which
      have different roles in the structural organization and functions of the protein.
      It is suggested that the tetramers are stabilized through interactions involving
      the second domain (residues 64-104) while assembly into the octamers and higher
      polymers requires hydrophobic interactions involving the N-terminal domain.
      Deletion of parts of this domain by site directed mutagenesis revealed that
      residues 46-63 play a critical role in the assembly. Current research aims to
      identify the specific amino acids involved.

PMID- 9650081
TI  - Mutation of alpha B-crystallin: effects on chaperone-like activity.
AB  - A recent paper by Plater et al. [20], showed that the mutation of a single
      phenylalanine residue F27R in mouse alpha B completely abolished the chaperone
      like property of alpha-crystallin when assayed with insulin at 25 degrees C or
      with gamma-crystallin at 66 degrees C. We have produced the same mutation as well
      as some additional mutations in human alpha B-crystallin. Our data suggest that
      the F27R mutation effected the thermal stability of alpha B-crystallin making it
      unstable at temperatures > or = 60 degrees C. In agreement with the published
      work, at these temperatures the F27R human recombinant alpha B-crystallin does
      not protect the target protein from aggregation. When assayed with insulin or
      alpha-lactalbumin at 25 or 37 degrees C, however, there were no differences in
      the protective abilities between the native alpha B-crystallin or the F27R
      mutated human alpha B-crystallin. Several other multiple mutations involving
      proline residues were also produced. These mutations did not effect the chaperone
      like properties of human alpha B-crystallin, but some of them did effect the
      native molecular weight size as judged by gel filtration chromatography.

PMID- 9650082
TI  - Structural perturbation of alpha-crystallin and its chaperone-like activity.
AB  - alpha-Crystallin is a multimeric lenticular protein that has recently been shown
      to be expressed in several non-lenticular tissues as well. It is shown to prevent
      aggregation of non-native proteins as a molecular chaperone. By using a non
      thermal aggregation model, we could show that this process is temperature
      dependent. We investigated the chaperone-like activity of alpha-crystallin
      towards photo-induced aggregation of gamma-crystallin, aggregation of insulin and
      on the refolding induced aggregation of beta- and gamma-crystallins. We observed
      that alpha-crystallin could prevent photo-aggregation of gamma-crystallin and
      this chaperone-like activity of alpha-crystallin is enhanced several fold at
      temperatures above 30 degrees C. This enhancement parallels the exposure of its
      hydrophobic surfaces as a function of temperature, probed using hydrophobic
      fluorescent probes such as pyrene and 8-anilinonaphthalene-1-sulfonate. We,
      therefore, concluded that alpha-crystallin prevents the aggregation of other
      proteins by providing appropriately placed hydrophobic surfaces; a structural
      transition above 30 degrees C involving enhanced or re-organized hydrophobic
      surfaces of alpha-crystallin is important for its chaperone-like activity. We
      also addressed the issue of conformational aspects of target proteins and found
      that their aggregation prone molten globule states bind to alpha-crystallin. We
      trace these developments and discuss some new lines that suggest the role of
      tertiary structural aspects in the chaperone process.

PMID- 9650083
TI  - Environmental factors influencing the chaperone-like activity of alpha
      crystallin.
AB  - The effects of mild environmental changes (e.g. the addition of divalent cations
      or EDTA, as well as variations of buffer pH) on the heat stability and chaperone
      like activity of native alpha-crystallin, and denatured-renatured alpha
      crystallin in the native molar isoform ratio, have been investigated using
      circular dichroism (CD) spectropolarimetry and functional assays. The presence or
      absence of divalent cations has little or no effect on the secondary structure of
      renatured samples, although chaperone-like activity levels can vary widely; the
      only relevant spectral difference observed is a loss of some alpha-helical
      content in all the renatured samples relative to the native protein, but this
      change has no impact on function. The range of concentration over which the
      inhibitory Mg2+ effect is observed is 10-fold higher for dialyzed fresh protein
      than for protein renatured into buffers containing Mg2+, but for both sets of
      samples, the full effect is established below physiological Mg2+ concentrations.
      Renaturing into various pH buffers, in contrast, affects both heat stability and
      chaperone-like activity below pH 7.0, with essentially no functionality observed
      at pH 6.0. CD spectra of these samples indicate that acidic conditions lead to
      some degree of unfolding, and that this unfolding correlates directly with
      functionality. Similar results are obtained for fresh protein dialyzed against
      these pH levels. Overall, these results suggest that heat stability is a function
      of the protein's secondary structure and folding state, while chaperone-like
      activity is primarily a function of factors at the tertiary and quaternary levels
      of organization.

PMID- 9650084
TI  - Protection of enzymes by alpha-crystallin acting as a molecular chaperone.
AB  - How can enzymes function in the centre of a crowded lens over the many decades of
      an individual's life when the same proteins are usually turned over in a period
      of days or h in most other tissues? The discovery that alpha-crystallin could
      function as a molecular chaperone in-vitro has led to the hypothesis that alpha
      crystallin could protect enzyme activities against various stresses. In the
      laboratory the authors have focused on the effect of alpha-crystallin on the
      activity of enzymes upon exposure to a chemical or thermal stress. The authors
      have demonstrated that enzymes are rapidly inactivated by sugars, sugar
      phosphates, steroids and cyanate. These compounds are elevated in diseases such
      as diabetes, diarrhoea and renal failure, all of which are risk factors for
      cataract. alpha-Crystallin has been shown to protect specifically against both
      chemically- and thermally-induced inactivation. Some enzymes are protected with a
      stoichiometry of one or two enzyme molecules protected per alpha-crystallin
      aggregate, consistent with a chaperone-like structure. However with other enzymes
      a more efficient protection occurs consistent with a micellar structure or
      binding on the outside of alpha-crystallin molecules. Investigation of complex
      formation indicates that although stable complex formation between enzymes and
      alpha-crystallin may be involved in protection of enzymes against thermal
      inactivation, protection against chemically-induced inactivation may be more
      dynamic in nature.

PMID- 9650085
TI  - Phosphorylations of alpha A- and alpha B-crystallin.
AB  - In addition to being refractive proteins in the vertebrate lens, the two alpha
      crystallin polypeptides (alpha A and alpha B) are also molecular chaperones that
      can protect proteins from thermal aggregation. The alpha B-crystallin
      polypeptide, a functional member of the small heat shock family, is expressed in
      many tissues in a developmentally regulated fashion, is stress-inducible, and is
      overexpressed in many degenerative diseases and some tumors indicating that it
      plays multiple roles. One possible clue to alpha-crystallin functions is the fact
      that both polypeptides are phosphorylated on serine residues by cAMP-dependent
      and cAMP-independent mechanisms. The cAMP-independent pathway is an
      autophosphorylation that has been demonstrated in vitro, depends on magnesium and
      requires cleavage of ATP. Disaggregation of alpha A-, but not alpha B-crystallin
      into tetramers results in an appreciable increase in autophosphorylation
      activity, reminiscent of other heat shock proteins, and suggests the possibility
      that changes in the aggregation state of alpha A-crystallin are involved in yet
      undiscovered signal transduction pathways. The alpha-crystallin polypeptides
      differ with respect to their abilities to undergo cAMP-dependent phosphorylation,
      with preference given to the alpha B-crystallin chain. These differences and
      complexities in alpha-crystallin phosphorylations, coupled with the differences
      in expression patterns of the two alpha-crystallin polypeptides, are consistent
      with the idea that each polypeptide has distinctive structural and metabolic
      roles.

PMID- 9650086
TI  - Interaction of DNA with bovine lens alpha-crystallin: its functional
      implications.
AB  - Under normal conditions, lens aggregates of alpha-crystallin subunits, alpha A
      and alpha B, are found in the cytoplasm. However, during stress in nonlenticular
      tissues, alpha B translocates to the nucleus. A sequence study revealed that both
      subunits share a consensus sequence with other DNA binding proteins. These
      observations prompted us to investigate DNA binding with alpha-crystallin by UV
      mediated photo-crosslinking. The data show that both single and double stranded
      DNA crosslink mainly with tetramers of alpha-crystallin subunits. The formation
      of tetramers appears to modify alpha-crystallin interactive properties and,
      therefore, its induction may have functional significance. These observations
      suggest that alpha-crystallin may have a nuclear function which includes DNA
      binding.

PMID- 9650087
TI  - Evidence for the participation of alpha B-crystallin in human age-related nuclear
      cataract.
AB  - The aim of this study was to determine if the unusual coloured species
      characteristic of age-related nuclear cataract could be localised to specific
      residues of the crystallins. The insoluble, crosslinked and coloured cataract
      protein fraction (CPF) was isolated from cataract human lenses. Using a
      combination of tryptic digestion, gel filtration and multiple reversed phase high
      performance liquid chromatography (RP-HPLC), coloured peaks were isolated and
      subjected to amino acid sequence analysis. With these techniques, it was hoped to
      identify and locate the modified residues. Sequence information was obtained on
      16 'coloured' peptides. Many of the peptides were found to be derived from alpha
      B-crystallin. When redundancies are taken into account, six distinctive peptides
      were found to be derived from alpha B-crystallin; one from beta B1-crystallin,
      two from beta A3/A1-crystallin and three from gamma S-crystallin. Three sites of
      possible crystallin residue isomerisation to modification were detected in the
      alpha B- and beta A3/beta A1-crystallins, including probable asp isomerisation at
      residues 25 and 36 in alpha B-crystallin. Since the CPF is unique to nuclear
      cataract lenses, these data suggest that alpha-crystallin, and alpha B-crystallin
      in particular, may be implicated in the cataract process. This finding supports
      that of a recent study on cataract proteins using pronase digestion [Chen YC,
      Reid GE, Simpson RJ, Truscott RJW. Exp Eye Res 1997;65:835.]

PMID- 9650088
TI  - The possible role of alpha-crystallins in human senile cataractogenesis.
AB  - alpha-Crystallins possess molecular chaperone properties and are one of the most
      abundant of the lenticular proteins. Posttranslational modifications of these
      proteins have been implicated as a possible etiology of human cataracts. This
      article will review current knowledge concerning the effects of known
      posttranslational modifications upon the molecular chaperone properties and
      aggregation behavior of alpha-A and alpha-B crystallin. Based upon these effects,
      experimental approaches will be discussed that may be useful in the development
      of reagents that may selectively inhibit the cataractogenic process in the aging
      human lens.

PMID- 9650089
TI  - Recombinant adenovirus encoding gp100 modulates experimental melanin-protein
      induced uveitis (EMIU).
AB  - Experimental melanin-protein induced uveitis (EMIU) is a T-cell mediated
      autoimmune uveitis induced by immunization with bovine uveal melanin protein.
      Gp100, a melanocyte lineage-specific protein, is identified as a human melanoma
      antigen. A recombinant adenovirus construct encoding gp100 (Ad2CMV-gp100) has
      been used as a vaccine for cancer therapy. This study examines the effect of
      Ad2CMV-gp100 on EMIU. To induce EMIU, rats were injected intraperitoneally on day
      7 before immunization with ad2CMV-gp100, control adenovirus encoding LacZ (Ad2CMV
      LacZ), or no virus. On day 21 after immunization, the right eye was processed for
      histology and the left eye was analysed for cytokines by quantitative reverse
      transcriptase-polymerase chain reaction. Western blot analysis showed that uveal
      melanin-protein contains gp100. In three independent experiments, ocular
      inflammation was significantly suppressed, and expression of ocular IL-12p40 mRNA
      was much lower in the rats which received Ad2CMV-gp100 before immunization than
      in those that received Ad2CMV-LacZ or no virus. No abnormalities developed in
      rats which received Ad2CMV-gp100 or Ad2CMV-LacZ alone. Therefore, Ad2CMV-gp100
      injection prevents the development of EMIU, at least in part, through cytokine
      regulation.

PMID- 9650090
TI  - Inhibition of the development of spontaneous autoimmune thyroiditis in the obese
      strain (OS) chickens by in vivo treatment with anti-CD4 or anti-CD8 antibodies.
AB  - The involvement of CD4+ and CD8+ T cells in pathogenesis of spontaneous
      autoimmune thyroiditis (SAT) in obese strain (OS) chickens has not been studied
      in depth until now. We depleted CD4+ or CD8+ T cells in OS chickens by treatment
      with murine monoclonal anti-CD4 or anti-CD8 antibodies at 3 day intervals
      beginning at hatching. The birds were killed at 19-25 days of age. Treatment with
      anti-CD4 antibody completely prevented SAT development, while treatment with anti
      CD8 antibody partially inhibited SAT. These results show the critical role of
      CD4+ T cells in the development of SAT in OS chickens, and indicate that CD8+ T
      cells are also involved in SAT pathogenesis.

PMID- 9650091
TI  - Protection from insulin dependent diabetes mellitus afforded by insulin antigens
      in incomplete Freund's adjuvant depends on route of administration.
AB  - Several islet antigens have been shown to modify the time of onset and severity
      of spontaneous insulin dependent diabetes mellitus (IDDM) in NOD (non-obese
      diabetic) mice. Oral, intravenous and intra-nasal administration of insulin and
      glutamic acid decarboxylase (GAD) or their derived peptides have all been shown
      to be effective to differing degrees in reducing the incidence and delaying the
      onset of diabetes in this mouse model of the disease. Incomplete Freund's
      Adjuvant (IFA) has also played a key role in tolerance when co-administered with
      insulin peptides subcutaneously. We show that route of administration may be of
      crucial importance, since although insulin B chain and the B9-23 peptide given in
      IFA subcutaneously protected (either partially or completely) from IDDM, when
      given intraperitoneally they completely failed to modify the disease.

PMID- 9650092
TI  - Induction of IgG rheumatoid factor (RF) production by antibody-antibody (RF-like)
      immune complexes: the role of T cells, complement and Fc gamma receptors.
AB  - Rheumatoid factors (RF) are autoantibodies with specificity for the constant
      regions of IgG molecules. They are found in several immunopathological diseases.
      The mechanism(s) by which these autoantibodies are produced is largely unknown.
      We have previously shown that a single injection of RF-like immune complexes
      (ICs) into mice selectively induced an intense IgG1-antibody production with RF
      activity. This response was sustained for several months and did not resemble a
      conventional immune response to an antigen or other immune complexes. In the
      present study, we sought to elucidate the mechanism for the IgG1 RF response to
      RF-like ICs. Therefore, the roles of CD4+ T cells, complement and Fc gamma
      receptors were analysed. In order to characterize the role of CD4+ T cells, RF
      like induced IgG1-RF production was analysed in NZB mice treated with a
      monoclonal antibody (mAb) against the CD4 molecule, which resulted in complete
      abrogation of IgG1 RF production. To evaluate the importance of Fc gamma Rs, the
      effect of RF-like ICs was tested in mice deficient for RF gamma RI/III. A
      significant decrease in the numbers of IgG1 antibody secreting cells, as well as
      in serum IgG1 RF levels, was found in the deficient mice, as compared with their
      normal outbred littermates. The role of complement in RF-like ICs mediated IgG1
      RF was tested in complement depleted NZB mice, using Cobra venom factor. The IgG1
      RF response in complement depleted and intact mice was comparable. Thus, our
      results demonstrate that RF-like immune complexes selectively induce an Fc gamma
      R-dependent, complement independent antibody response in mice.

PMID- 9650093
TI  - Adhesion elicits an intrinsic defect in interleukin-1 expression by macrophages
      from autoimmune-prone MRL mice.
AB  - Macrophages (m phi) from prediseased autoimmune-prone MRL/+ and MRL/ lpr mice
      have a marked defect in endotoxin (LPS)-induced expression of several cytokines
      including interleukin 1 (IL-1). The progressive nature of this defect over time
      suggests that it may develop in response to specific extracellular stimuli. In
      this report, we show that adhesion is an essential factor for the development of
      aberrant IL-1 expression by m phi from autoimmune-prone MRL mice. Thus, when
      MRL/+ m phi were allowed to adhere before being stimulated with LPS, they
      demonstrated a striking defect in expression of both IL-1 message and protein in
      comparison with multiple normal strains. In marked contrast, when MRL/+ m phi
      were maintained in a non-adherent state by culture on agarose, the IL-1 defect
      was not evident and IL-1 expression was restored to nearly normal levels. Since
      an identical defect in IL-1 expression was found when MRL/+ m phi were cultured
      on a variety of extracellular matrix proteins (including laminin, fibronectin,
      type I collagen, and type IV collagen), it appears that IL-1 underexpression is
      dependent on the adhesive state per se rather than on engagement of any one
      specific adhesion receptor. Moreover, the cytoskeletal inhibitor cytochalasin D
      had no effect on the magnitude of the defect, indicating that the adhesion
      dependent signaling events necessary to elicit IL-1 underexpression are
      independent of cytoskeletal rearrangement. Taken together, these results indicate
      that m phi from autoimmune prone MRL/+ mice have an adhesion-dependent signaling
      abnormality that leads to profound underexpression of the cytokine IL-1.

PMID- 9650094
TI  - Natural and disease associated autoantibodies to the autoantigen,
      dihydrolipoamide acetyltransferase, recognise different epitopes.
AB  - Naturally occurring autoantibodies are ubiquitous and may serve physiological
      functions. We examined the relationship of natural and disease-associated
      autoantibodies in the context of autoantibodies to dihydrolipoamide
      acetyltransferase, the 74 kDa E2 sub-unit of the mitochondrial pyruvate
      dehydrogenase complex (PDC-E2), characteristic of primary biliary cirrhosis
      (PBC). We tested for natural autoantibodies to PDC-E2 in normal sera, and
      compared epitopes recognised by natural and disease-associated autoantibodies.
      Methods included affinity purification of anti-PDC-E2 from normal and PBC sera,
      ELISA and immunoblotting, capacity of antibodies to inhibit the enzyme function
      of the pyruvate dehydrogenase complex (PDC), use of F(ab)2 fragments of anti-PDC
      E2 in inhibition assays, and testing affinity purified anti-PDC-E2 on peptide
      fragments of PDC-E2. We found that natural auto-antibodies to PDC-E2 of IgG class
      were demonstrable in all healthy human sera (10/10). However, their reactivity
      differed from that of disease-associated autoantibodies, in that anti-PDC-E2 from
      normal serum failed to inhibit the catalytic activity of PDC; and F(ab)2
      fragments from PBC sera potently blocked the binding of anti-PDC-E2 from PBC sera
      to PDC-E2, but not the binding of natural anti-PDC-E2 to PDC-E2. Immunoblotting
      on fragments of PDC-E2 using affinity-purified preparations from PBC sera and
      normal sera failed to provide evidence for gross differences in epitope
      reactivity. We conclude that normal human sera contain natural IgG autoantibodies
      to the immunodominant inner lipoyl domain of PDC-E2, as seen characteristically
      in PBC. However, there is evidence for differences in fine epitope recognition.

PMID- 9650095
TI  - Cross-reactivity of antibodies immunoadsorbed to laminin with recombinant human
      La (SS-B) protein.
AB  - Anti-La (SS-B) antibodies cross-reacting with mouse B1 laminin were reported in
      sera of patients with systemic lupus erythematosus. However, the common epitope
      had not been characterized. Immunoblotting conditions were established, allowing
      detection and elution of anti-La (SS-B)/laminin cross-reacting antibodies.
      Antibodies adsorbed to mouse B1 laminin represented a subclass of anti-La
      antibodies. They strongly reacted with human full length recombinant La protein.
      However, they failed to react with either an N-terminal La peptide consisting of
      amino acids 1-192 or a C-terminal La peptide starting at methionine 223, while
      they still reacted with recombinant La peptides consisting of the amino acids 1
      341 or starting at 192. These data indicate that the La (SS-B)/laminin epitope is
      located between amino acids 192-223 of human La protein, which includes the amino
      acids EAKLRA, common to the nuclear autoantigen La (SS-B) and the human or mouse
      B1 laminin.

PMID- 9650096
TI  - Cloned T cells from a recent onset IDDM patient reactive with insulin B-chain.
AB  - Insulin-dependent diabetes mellitus (IDDM) results from selective autoimmune
      destruction of insulin producing beta-cells. T-cell reactivity and autoantibodies
      to several islet proteins such as insulin, GAD and IA-2 are associated with IDDM
      in mice and men. In NOD mice, the majority of T cells from insulitis specifically
      recognize the insulin B-chain peptide amino acid 9-22, in contrast to the
      periphery where the precursor frequency is much lower. It is important to note
      that these cells are diabetogenic. Surprisingly, the same insulin B-chain region
      contains epitopes recognized by protective T cells. In fact, autoimmune diabetes
      in NOD mice could be prevented by prophylactic treatment with this immunodominant
      T-cell epitope. In humans, however, no immunodominant regions of insulin have yet
      been defined. We have isolated and characterized a human insulin-specific T-cell
      clone that was derived from peripheral blood of a newly diagnosed IDDM patient.
      This patient displayed weakly positive primary T-cell responses to insulin. The
      peptide recognized by the clone was mapped to the insulin B chain (B:11-27).
      Functionally, the human insulin-specific CD4+ T cells displayed a Th1/0 like
      cytokine profile and were restricted by HLA-DR. The previously proposed
      alternative superantigen-like binding of insulin-B chain peptide outside of the
      peptide binding groove of HLA-DR could not be confirmed, since T-cell recognition
      was inhibited in competition experiments of insulin-B chain peptide with HLA-DR16
      binding influenza peptide HA307-319. Our results indicate that human clonal T
      cells isolated from a recent onset IDDM patient recognize an epitope overlapping
      with the insulin B-chain region that is immunodominant and potentially
      therapeutic in NOD mice. This observation may be useful in studying the role of
      insulin-specific T cells in IDDM, and may eventually help to establish peptide
      based immunotherapies in IDDM.

PMID- 9650097
TI  - The gene responsible for autoimmune polyglandular syndrome type 1 maps to
      chromosome 21q22.3 in US patients.
AB  - Autoimmune polyglandular syndrome type 1 [APS-1] comprises multiple organ
      specific autoimmunities such as acquired hypoparathyroidism and autoimmune
      Addison's disease, and a predisposition to certain infections such as chronic
      mucocutaneous candidiasis. An APS-1 candidate gene was assigned to chromosome
      21q22.3 by linkage analyses in patients with APS-1 from Finland. To examine the
      influence of ethnic and geographic differences on the location of the candidate
      gene locus, we studied 24 US patients with APS-1 by microsatellite marker typing,
      using five microsatellite markers, D21S49, PFKL, D21S171, D21S1903 and CD18,
      selected from chromosome 21q22.3. By allelic association analyses, the
      frequencies of allele number 5 for D21S171 and allele number 8 for D21S1903 were
      significantly higher in the 24 patients with APS-1 than in 33 controls (33/48 vs.
      31/66, P = 0.0207, X2 = 5.35; 12/48 vs. 7/66, P = 0.0418, X2 = 4.15
      respectively). The frequency of homozygosity for allele number 5 of D21S171 was
      also significantly higher in the patients than in controls, 15/24 vs. 9/33 (P =
      0.0078, X2 = 7.07). Maximum lod scores detected for the five markers in nine
      families (containing 15 of the patients with APS-1) were: 2.384 for D21S49, 3.144
      for PFKL, 3.506 for D21S171, 4.329 for D21S1903, and 1.130 for CD18. These
      results confirm the linkage of the candidate APS-1 gene to 21q22.3 in US APS-1
      patients, and suggest that the candidate gene is located near the D21S1903
      marker. The demonstration of the location of the APS-1 candidate gene to 21q22.3
      in an out-bred heterogeneous patient population should promote the physical
      mapping of the responsible gene.

PMID- 9650098
TI  - Antineutrophil cytoplasmic autoantibodies (ANCA) in children with cystic
      fibrosis.
AB  - Anti-neutrophil cytoplasmic antibodies (ANCA) represent a useful diagnostic tool
      in patients with small vessel vasculitis. Circulating ANCA specific for
      bactericidal/permeability increasing protein (BPI) have been recently reported in
      adult patients with cystic fibrosis (CF), an autosomal recessive disorder caused
      by mutations in the cystic fibrosis transmembrane regulator (CFTR) gene with
      consequent impaired function of a transmembrane chloride channel. To contribute
      to the better understanding of the significance of ANCA in this disease, we
      investigated ANCA presence and antigenic specificity in children with CF. Results
      were correlated with clinical status, immunological data, age and genotype. The
      indirect immunofluorescence pattern of a total of 71 children with CF indicated
      that 31 were c-ANCA positive, while seven were p-ANCA positive. In further ELISA
      studies of ANCA antigenic specificity, 51 out of 66 investigated samples were
      positive for BPI, and 14 out of 28 were positive for proteinase 3 (PR3). We found
      an association between levels of antibodies against PR3 with age and Pseudomonas
      infection. We did not, however, find any correlation between CFTR genotypes,
      Pseudomonas infection or paediatric parameters and the level of anti-BPI
      antibodies. High positivity of anti-BPI antibodies were seen even among the
      youngest CF patients, before the development of clinical signs of CF, indicating
      that formation of ANCA might be a very early event in the disease. Both anti-BPI
      and anti-PR3 antibodies may play a significant, although variable role, in the
      pathogenesis of CF.

PMID- 9650099
TI  - Response of CD4+ T cells from myasthenic patients and healthy subjects of
      biosynthetic and synthetic sequences of the nicotinic acetylcholine receptor.
AB  - We investigated the suitability of pools of overlapping synthetic peptides
      spanning the complete alpha 1 subunit sequence of the human muscle acetylcholine
      receptor (AChR) (alpha 1 pool) or the extracellular domain (residues 1-218, alpha
      11-218 pool), and of biosynthetic alpha 1 constructs from E. coli, as stimulants
      of human CD4+ cells from myasthenia gravis (MG) patients and healthy subjects. A
      construct corresponding to residues alpha 11-209 was obtained as solubilized
      inclusion bodies (ib alpha 11-209), or purified by SDS gel electrophoresis (pur
      alpha 11-209). A second construct included the extracellular, cytoplasmic and
      carboxylterminal domains plus histidine residues, and was obtained as inclusion
      bodies (ib alpha 1NoTrans) or purified by gel permeation and histidine tag
      affinity chromatography (pur alpha 1NoTrans). A biosynthetic extracellular domain
      of the neuronal AChR alpha 7 subunit (ib alpha 71-206) isolated from E. coli as
      inclusion bodies served as control for bacterial contaminants. We used ib alpha
      11-209, pur alpha 11-209 and peptide pools to propagate CD4+ lines from two MG
      patients. The lines obtained using pur alpha 11-209 and the peptide pools
      recognized the peptide pools and alpha 1 constructs tested well, but ib alpha 71
      206 poorly or not at all. These lines recognized peptides known to form CD4+
      epitopes in these patients. The ib alpha 11-209 lines recognized ib alpha 11-209
      and ib alpha 71-206 strongly, but recognized poorly pur alpha 11-209 and the
      alpha 11-218 pool. We propagated T-cell lines from a healthy subject using pur
      alpha 11-209 and ib alpha 11-209. The pur alpha 11-209 line recognized pur alpha
      11-209 and the alpha 11-218 pool, but not ib alpha 11-209 or ib alpha 71-206. The
      ib alpha 11-209 line recognized ib alpha 11-209 and ib alpha 71-206, but not pur
      alpha 11-209 or the alpha 11-218 pool. We tested blood CD4+ cells from six MG
      patients and eight healthy subjects with ib alpha 11-209, pur alpha 11-209, the
      alpha 11-218 pool and--in the healthy subjects--also ib alpha 71-206, ib alpha
      1NoTrans and pur alpha 1NoTrans. In both populations, the alpha 11-218 pool
      elicited low and sporadic responses, while the constructs elicited clear
      responses that were frequently higher for ib alpha 11-209 than pur alpha 11-209.
      The responses to ib alpha 71-206 were strong and comparable to those to ib alpha
      11-209, ib alpha 1NoTrans, and pur alpha 1NoTrans. These results indicate that
      even purified constructs from E. coli contain bacterial contaminants recognized
      by CD4+ cells. They should not be used to test unselected blood CD4+ cells,
      because they may evoke strong CD4+ responses to the bacterial antigens. Purified
      recombinant sequences may be suitable for propagation of CD4+ cell lines, if the
      specificity of the lines can be verified using different antigen preparations.
      Short synthetic peptide sequences can be safely used for propagation of specific
      CD4+ cells. Although they are poor stimulants for unselected blood CD4+ cells,
      the low responses they elicit are probably due to these cells.

PMID- 9650100
TI  - ESR and U-series analyses of teeth from the palaeoanthropological site of Hexian,
      Anhui Province, China.
AB  - ESR and U-series analyses of teeth from the palaeoanthropological site of Hexian
      which contained Homo erectus remains, illustrate the limited effectiveness of
      stand-alone ESR and U-series age estimates on faunal materials. The problem lies
      in the unknown U-uptake history causing very large uncertainties in the age
      results of both techniques. This study demonstrates the particular strength that
      lies in the integration of ESR and U-series dating analyses allowing the
      estimation of the U-uptake history. We obtained a combined ESR/U-series age
      estimate of 412 +/- 25 ka (average of six analyses on two teeth). This pinpoints
      the deposition of the faunal remains to the time of the transition between oxygen
      isotope stages 12 and 11. This is in agreement with the faunal composition which
      show a mixture of cold adapted northern mammals and more subtropical-tropical
      southern elements. The age also implies that the advanced Hexian Homo erectus
      occurred at a similar time as the less advanced Homo erectus specimens at
      Locality 1 at Zhoukoudian (LI-LIII).

PMID- 9650101
TI  - Archaeological predictions for hominid land use in the paleo-Olduvai Basin,
      Tanzania, during lowermost Bed II times.
AB  - We present a preliminary predictive model of Oldowan stone artefact and scavenged
      larger mammal bone assemblages for 11 landscape facets modeled earlier to occur
      across a large portion (> 300 km2) of the paleo-Olduvai Basin during lowermost
      Bed II times. This second phase of model-building is based on our earlier
      characterizations of the basin's landscape ecostructure and the inter-facet
      distribution of key resources and hazards probably encountered by Late Pliocene
      hominids (Peters & Blumenschine, 1995, 1996). Our current extension of the model
      of hominid-landscape interactions specifies additional theoretical components,
      including: (1) the assumed capabilities of Oldowan hominids (presumably Homo
      habilis, primarily); (2) the landscape-facet-specific tasks they carried out; (3)
      the immediate stone and bone task residues they produced; and (4) the predicted
      composition, condition, density, and clustering of stone artefact and butchered
      and unbutchered bone assemblages for each facet. We develop ecological linkages
      between these new and formerly reported modeling components, the most fundamental
      of which is the facet-specific degree of tree/shrub cover abundance, and the
      correlated degree of competition among larger carnivores and hominids for
      scavengeable larger mammal carcasses. These factors condition variability among
      landscape facets in scavenging opportunities encountered by hominids, which in
      our model is the major predictor of bone and stone artefact assemblage
      composition. The predictive value of scavenging reflects the bias of
      paleoanthropological traces toward technology and butchery in their landscape
      context, but the model is surprisingly insensitive to what are usually thought to
      be critical social components of hominid land use. The predictions for the traces
      of hominid-landscape interactions modeled herein can be tested in the future
      against the landscape archaeological sample being excavated from lowermost Bed II
      by the Olduvai Landscape Paleoanthropology Project.

PMID- 9650102
TI  - Theropithecus atlanticus (Thomas, 1884) (Primates: Cercopithecidae) from the late
      Pliocene of Ahl al Oughlam, Casablanca, Morocco.
AB  - The site of Ahl al Oughlam near Casablanca, Morocco, dated to ca. 2.5 Ma, has
      yielded a good sample of Theropithecus atlanticus (Thomas, 1884), a North African
      late Pliocene species previously known only by its holotype, a lower molar from
      Algeria. Theropithecus atlanticus, which can now be much better defined, is
      clearly distinct from other species of the genus, which is thus more diverse than
      previously thought. The mandible of T. atlanticus has a very characteristic deep
      and long post-molar sulcus and a deep and well excavated supra-lateral triangular
      depression of the ramus, with a sharp postero-inferior ridge. The upper and lower
      canines are rather large but low. The male P3 is very wide, with well developed
      posterior crests; the P4 is rounded, with a large talonid and weak notches and
      clefts. Median lingual notches of the lower molars form an acute angle. Although
      our incomplete knowledge of T. atlanticus precludes a detailed phylogenetic
      analysis, we suggest that it arose by cladogenesis from the T. darti-T. oswaldi
      lineage; it is replaced by the latter species in the Pleistocene.

PMID- 9650103
TI  - Late Pleistocene human population bottlenecks, volcanic winter, and
      differentiation of modern humans.
AB  - The "Weak Garden of Eden" model for the origin and dispersal of modern humans
      (Harpending et al., 1993) posits that modern humans spread into separate regions
      from a restricted source, around 100 ka (thousand years ago), then passed through
      population bottlenecks. Around 50 ka, dramatic growth occurred within dispersed
      populations that were genetically isolated from each other. Population growth
      began earliest in Africa and later in Eurasia and is hypothesized to have been
      caused by the invention and spread of a more efficient Later Stone Age/Upper
      Paleolithic technology, which developed in equatorial Africa. Climatic and
      geological evidence suggest an alternative hypothesis for Late Pleistocene
      population bottlenecks and releases. The last glacial period was preceded by one
      thousand years of the coldest temperatures of the Later Pleistocene
      (approximately 71-70 ka), apparently caused by the eruption of Toba, Sumatra.
      Toba was the largest known explosive eruption of the Quaternary. Toba's volcanic
      winter could have decimated most modern human populations, especially outside of
      isolated tropical refugia. Release from the bottleneck could have occurred either
      at the end of this hypercold phase, or 10,000 years later, at the transition from
      cold oxygen isotope stage 4 to warmer stage 3. The largest populations surviving
      through the bottleneck should have been found in the largest tropical refugia,
      and thus in equatorial Africa. High genetic diversity in modern Africans may thus
      reflect a less severe bottleneck rather than earlier population growth. Volcanic
      winter may have reduced populations to levels low enough for founder effects,
      genetic drift and local adaptations to produce rapid population differentiation.
      If Toba caused the bottlenecks, then modern human races may have differentiated
      abruptly, only 70 thousand years ago.

PMID- 9650104
TI  - Multivariate analyses of the hominid ulna from Klasies River mouth.

PMID- 9650105
TI  - A newly discovered Kenyapithecus skeleton and its implications for the evolution
      of positional behavior in Miocene East African hominoids.

PMID- 9650106
TI  - Ethics and law for medical students: the core curriculum.

PMID- 9650107
TI  - Palliative care--a euthanasia-free zone?

PMID- 9650108
TI  - Reaching targets in the national cervical screening programme: are current
      practices unethical?
AB  - The principle of informed consent is now well established within the National
      Health Service (NHS) in relation to any type of medical treatment. However, this
      ethical principle appears to be far less well established in relation to medical
      screening programmes such as Britain's national cervical screening programme.
      This article will critically examine the case for health care providers
      vigorously pursuing women to accept an invitation to be screened. It will discuss
      the type of information which women would need in order to make an informed
      decision about whether or not to be screened. The lack of such information in
      current patient leaflets on the "smear test" will then be documented. Finally,
      the article will explore possible ways of maximising women's autonomy in relation
      to the cervical screening programme without sacrificing any of its main benefits.

PMID- 9650109
TI  - Empirical examination of the ability of children to consent to clinical research.
AB  - This study examined the quality of children's assent to a clinical trial. In
      subjects younger than 9 years of age, understanding of most aspects of the study
      was found to be poor to non-existent. Understanding of procedures was poor in
      almost all subjects. In addition, voluntariness may have been compromised in many
      subjects by their belief that failure to complete the study would displease
      others. If the fact that a child's assent has been obtained is used to justify
      the exposure of that child to the potential harm of a non-therapeutic blood
      sample, the assent must be meaningful. In the nutrition study observed here, the
      quality of the assent of children younger than 9 years of age was very poor. The
      assent therefore did not provide a valid justification for requesting a blood
      sample from these children. This study indicates that most children younger than
      9 years of age cannot be expected to consent or assent to clinical research in a
      meaningful way. The current age of 7 years for initiating assent (in addition to
      parental consent) is possibly not appropriate and should be reconsidered.

PMID- 9650110
TI  - The subtle politics of organ donation: a proposal.
AB  - Organs available for transplantation are scarce and valuable medical resources
      and decisions about who is to receive them should not be made more difficult by
      complicated calculations of desert. Consideration of likely clinical outcome must
      always take priority when allocating such a precious resource otherwise there is
      a danger of wasting that resource. However, desert may be a relevant concern in
      decision-making where the clinical risk is identical between two or more
      potential recipients of organs. Unlikely as this scenario is, such a decision
      procedure makes clear the interdependence of organ recipient and organ donor and
      hints at potential disadvantages for those who are willing to accept but
      unwilling to donate organs (free-riders). A combined opting-out and preference
      system weakens many of the objections to opting-out systems and may make the
      decision to donate organs on behalf of their deceased relatives easier for
      families.

PMID- 9650111
TI  - Imaginary restrictions.
AB  - The role of literature and imagination in medicine and medical ethics is
      currently under discussion. This paper argues that the role of literature is not
      to furnish generalisable examples for guidance. Rather, engagement with
      literature parallels moral engagement with other people. The work of the
      imagination, in this context, is not to hypothesise, but to grant life to the
      characters and world of literature. In doing this, one may develop one's moral
      life.

PMID- 9650112
TI  - Narrative and knowledge development in medical ethics.
AB  - The role of individual life accounts has been promoted--largely through what has
      come to be described as narrative ethics-as important to the practice of medical
      ethics for a number of years. Beyond this the apparent incompatibility of
      personal stories with scientific procedure has limited their use. In this article
      I will argue that this represents a serious under-utilisation of a valuable
      method for researching ethical dilemmas and the settings in which these dilemmas
      are played out. Life stories need not simply provide a stimulus to scientific
      research but can in themselves yield intellectually robust evidence on the
      general as well as the particular. By drawing on the rigorous methods developed
      elsewhere, personal accounts not only allow us to "enter the world of the sick
      person" but allow us to do so in such a way as to contribute to empirical and
      theoretical knowledge.

PMID- 9650113
TI  - Balancing the quality of consent.
AB  - The rule that one must obtain informed consent is well established in medical
      ethics and an intrinsic part of clinical practice and of research in biomedicine.
      However, there is a tendency that the rule today is being applied too rigidly and
      with too little sensitivity to the values that are at stake in connection with
      different kinds of research protocols. It is here argued that the quality of
      consent needs to be balanced against variables such as degree of confidentiality
      and importance of values at stake, in order to be ethically acceptable.
      Appropriate information and consent procedures should be adjusted accordingly.
      Three levels are suggested, ranging from extensively informed consent with both
      written and oral information, through informed refusal with only a limited amount
      of information given to, at the other end of the scale, just making relevant
      information available.

PMID- 9650114
TI  - Teaching medical ethics and law within medical education: a model for the UK core
      curriculum.

PMID- 9650115
TI  - Ethical dilemmas in occupational therapy and physical therapy: a survey of
      practitioners in the UK National Health Service.
AB  - OBJECTIVES: To identify ethical dilemmas experienced by occupational and physical
      therapists working in the UK National Health Service (NHS). To compare ethical
      contexts, themes and principles across the two groups. DESIGN: A structured
      questionnaire was circulated to the managers of occupational and physical therapy
      services in England and Wales. SUBJECTS: The questionnaires were given to 238
      occupational and 249 physical therapists who conformed to set criteria. RESULTS:
      Ethical dilemmas experienced during the previous six months were reported by 118
      occupational and 107 physical therapists. The two groups were similar in age,
      grade, and years of experience. Fifty of the occupational therapy dilemmas
      occurred in mental health settings but no equivalent setting emerged for physical
      therapy. Different ethical themes emerged between the two groups, with the most
      common in occupational therapy being difficult/dangerous behaviour in patients
      and unprofessional staff behaviour, and for physical therapists resource
      limitations and treatment effectiveness. No differences were found in the ethical
      principles used. CONCLUSION: The ethical dilemmas reported by the therapists were
      primarily concerned with health care ethics, rather than the more dramatic ethics
      reported in much of the biomedical ethics literature. Differences were found
      between the two professional groups when ethical contexts and themes were
      compared but not when ethical principles were compared. This suggests that
      educators and researchers need to be aware of work settings and the
      interdisciplinary nature of employment as well as ethical principles held by
      individual therapists.

PMID- 9650116
TI  - Limits of neonatal treatment: a survey of attitudes in the Danish population.
AB  - OBJECTIVES: To study attitudes in the Danish population towards treatment of
      severely handicapped and extremely preterm infants and to define areas of
      consensus and controversy. DESIGN: Mail-delivered questionnaire. SETTING:
      Denmark. Survey sample--A random sample of 1080 persons aged from 18 to 45 years.
      RESULTS: The overall response rate was 68%. There was strong consensus (more than
      75% agreement) that life-prolonging treatment should be provided for an infant
      born after 24 weeks' gestation with respiratory distress and, for an infant with
      myelomeningocele, when the parents were in favour of treatment. Further, there
      was almost uniform agreement that not all infants should be treated no matter how
      serious the condition. Major controversies concerned the severity of a condition
      needed to justify omission of life-prolonging treatment, the role of parental
      attitude and the options in non-treatment cases. Forty-six per cent thought it
      ought to be legal to kill the infant in at least some of these cases. CONCLUSION:
      Although the study revealed wide divergences of opinion with regard to questions
      about limits of treatment and about end-of-life decisions it also showed that
      there was general acceptance both that life-prolonging treatment ought to be
      provided even in relatively severe cases if this was in accordance with parental
      wishes, and that life should not be saved at all costs.

PMID- 9650117
TI  - Is there a demand for a clinical ethics advisory service in the UK?

PMID- 9650118
TI  - ACE-inhibitors and progression of chronic renal insufficiency: a contribution of
      Italian clinical research.

PMID- 9650119
TI  - Neutrophils and acute ischemia-reperfusion injury.
AB  - Leukocyte infiltration in response to I/R injury is a well-known but poorly
      understood phenomenon. The contribution of neutrophils in this process is still
      controversial. Despite numerous data, little is known about exact numbers of
      infiltrating neutrophils. The role of monocytes/macrophages in this process is
      even more unclear. The role neutrophils in the kidney and other organs was
      reviewed. The variability in models and methods for neutrophil quantification
      were examined, along with carrying out a critical overview of depletion and anti
      adhesion approaches. Nevertheless, the exact role attributed to neutrophils in
      the I/R process remains unclear.

PMID- 9650120
TI  - Ischemic disease of the kidney: how and why to consider revascularization.
AB  - With increasingly accurate non-invasive tests, the clinician frequently discovers
      obstruction of the renal arteries by atherosclerosis. The decision to reverse
      this obstruction is not straightforward, particularly when blood pressure can be
      easily controlled with medications. Proper management of this problem requires
      knowledge of the accuracy of the diagnosis, the natural history of the disorder,
      and the outcomes of possible interventions. This review will emphasize the value
      of a variety of non-invasive tests, the consequences of allowing the arteries to
      remain obstructed, and the long-term results from reversing renal artery
      obstruction. Surgical and non-surgical interventions will be examined, including
      percutaneous angioplasty, angioplasty with wall stenting, surgical atherectomy,
      and surgical bypass procedures. In contemporary practice hypertension is
      routinely recognized and aggressively treated regardless of the etiology.
      Therefore preservation of kidney function is becoming an increasingly important
      clinical goal. This review will pursue a unified approach to renal artery
      obstruction and emphasize the goal of preserving glomerular filtration rate.

PMID- 9650121
TI  - Surgical complications of kidney transplantation.
AB  - Over the last 30 years, kidney transplantation has evolved tremendously, from an
      experimental procedure with barely 50% allograft acceptance to a highly refined
      management program with a success rate of 80-90%. Not only has the overall rate
      of complications decreased to less than 5%, due to more secure technical
      approaches, but also advances in immunosuppressive regimens have reduced the
      morbidity associated with the procedure. This contribution, addressing all stages
      of the transplant process (donor nephrectomy, benchwork preparation, and
      implantation) assesses potential pitfalls and technical misadventures that must
      be avoided in order to assure the patient of a complication-free course.

PMID- 9650122
TI  - Absence status: an overlooked cause of acute confusion in hemodialysis patients.
AB  - Epileptic seizures are a known complication of uremia, but non-convulsive
      seizures appear to be rare. We describe a patient with absence status presenting
      with acute confusion who responded well to intravenous diazepam. Attention is
      drawn to this rare cause of acute confusional state in the hemodialysis
      population.

PMID- 9650123
TI  - Analysis of 490 kidney biopsies: data from the United Arab Emirates Renal
      Diseases Registry.
AB  - There is little data on the spectrum of renal diseases in the United Arab
      Emirates. A renal diseases registry has been set up in an attempt to address this
      issue nationwide, and we report here the first outcome of this endeavor, a
      retrospective histopathologic analysis of 490 native kidney biopsies performed on
      adult patients presenting to four hospitals in the Emirate of Abu Dhabi from 1978
      to June 1996. The most common indication for a biopsy was the nephrotic syndrome
      (54.0%), followed by asymptomatic urinary abnormalities (29.7%), and chronic
      renal failure (12.7%). Primary glomerular disease accounted for 77.1% of all
      biopsies. Chronic proliferative glomerulonephritis as a group was the predominant
      pathology (36.2%), followed by idiopathic membranous glomerulopathy (20.1%),
      focal segmental glomerulosclerosis (18.3%), minimal change nephropathy (18.3%),
      and IgA nephropathy (6.3%). Of the patients with secondary kidney diseases, 33
      (40.7%) had systemic lupus erythematosis, 27 (33.3%) amyloidosis, 14 interstitial
      nephropathy, and seven diabetic nephropathy. Kidney biopsies of 187 patients with
      primary glomerular disease who presented with the nephrotic syndrome were
      analyzed. In this group idiopathic membranous glomerulopathy, proliferative
      glomerulonephritis, and minimal change glomerulopathy was found in almost equal
      proportions (28.3%, 26.6%, 26.2%) with focal segmental glomerulosclerosis (15.4%)
      accounting for the bulk of the remainder. Though the overall results of this
      analysis do not show any major differences in the spectrum of primary
      glomerulopathies in the United Arab Emirates compared with other countries, a
      slight tendency towards a higher frequency of focal segmental glomerulosclerosis
      among patients indigenous to the Arabian Peninsular (20.4%) deserves further
      evaluation.

PMID- 9650124
TI  - The nonselective adenosine antagonist theophylline does prevent renal dysfunction
      induced by radiographic contrast agents.
AB  - Radiocontrast agents (RCA) induce nephrotoxicity characterized by acute renal
      failure (ARF), which seems to be mediated partly by adenosine. ARF significantly
      influences erythropoietin (EPO) secretion and plasma renin activity (PRA). The
      present study assessed the influence of theophylline, a nonspecific adenosine
      receptor antagonist, on renal function, EPO secretion and PRA after the use of
      RCA. Fifty-eight patients underwent X-ray examinations with administration of
      RCA. Patients were randomized to receive either 165 mg of theophylline or placebo
      (saline) before the injection of 40 ml of high-osmolar contrast medium Plasma
      concentrations of EPO and PRA were assayed in blood samples drawn 2 hours before
      and 3, 6, 12 and 24 hours after RCA. Glomerular filtration rate, evaluated from
      endogenous creatinine clearance, urinary excretion of beta 2-microglobulin (beta
      2-M), Tamm-Horsfall protein (THP) and albumin were assessed one day before RCA,
      on the day of RCA injection and one day later. In patients not treated with
      theophylline, RCA injection was followed by a significant reduction of GFR and
      increased urinary excretion of both beta 2-M and THP, which declined or were
      normal one day later. Simultaneously there was a significant decrease of plasma
      EPO and PRA. Theophylline prevented the decline of GFR, the increase of urinary
      beta 2-M and THP and the reduction of plasma EPO and PRA. The drug did not
      influence urinary albumin excretion. We conclude that RCA-induced impairment of
      renal excretory, endocrine and tubular function can be prevented by giving
      theophylline before RCA. These results suggest that adenosine may play a role in
      the pathogenesis of RCA-induced nephropathy.

PMID- 9650125
TI  - Intravenous immunoglobulin induced-nephropathy: a complication of IVIG therapy.
AB  - Since the early 1950s, intravenous immunoglobulin (IVIG) preparations are being
      used in the treatment of hematologic, neurologic, nephrologic, autoimmune, and
      immunodeficiency disorders. Infusion of IVIG preparations may cause osmotic
      induced acute renal failure. Despite the fact that this entity has been reported
      previously, it is not a widely appreciated complication. A total of 22 reports
      involving 52 patients in whom renal failure occurred in association with IVIG
      infusion. The patients' ages ranged from 20 to 82 years. Thirty patients had
      preexisting renal insufficiency. Rise in serum creatinine was noted after 1-10
      days of IVIG infusion and creatinine returned to baseline within 2-60 days of
      discontinuation. One developed end stage renal disease. There were four
      fatalities related to complications of renal failure. Histopathology of renal
      tissue showed osmotically induced tubular injury (5 patients), tubular
      vacuolization (2 patients), tubulointerstitial infiltrate (1 patient), and
      cryoglobulin deposits (1 patient). There appears to be no direct relationship
      between the development of acute renal failure and the type of IVIG. However,
      underlying renal insufficiency increases the risk of renal failure. In view of
      the increasing use of IVIG preparations in medicine, it is imperative that
      clinicians be aware of this unusual form renal injury.

PMID- 9650126
TI  - Obstetric outcome in women who present with a reduction in fetal movements in the
      third trimester of pregnancy.
AB  - A complaint of decreased fetal movements is a common indication for the
      assessment of fetal well being. The aim of this study was to review the outcome
      of a group of women whose primary indication for referral was decreased fetal
      movements. Over a 20 month period, 435 patients were seen in the fetal assessment
      unit of an inner London teaching hospital, following a primary complaint of
      reduced fetal movements. Investigations included: the fetal abdominal
      circumference (AC), amniotic fluid volume (AFV), the umbilical artery pulsatility
      index (UAPI) derived from Doppler ultrasound waveforms and a computerised
      analysis of fetal heart rate (FHR) recordings or cardiotocograph (CTG). Outcome
      measures were: gestational age at delivery, Apgar score < 7 at 5 minutes,
      admission to the Special Care Baby Unit (SCBU), the need for delivery by an
      emergency cesarean section for fetal compromise (CSFC), and any perinatal deaths.
      A comparison of actual versus expected outcome for women with decreased fetal
      movement revealed the following relative risks, with the 95% confidence intervals
      (CI) in brackets; low 5 minute Apgar score 0.03 vs. 0.05 expected (CI = 0.01,
      0.05), SCBU admission, 0.06 vs. 0.07 (0.04, 0.08), and preterm delivery, 0.08 vs.
      0.11 (0.05, 0.10). Cesarean sections for fetal compromise, 0.07 vs. 0.053 (0.050
      0.096). The addition of FHR monitoring to standard ultrasound assessment of well
      being did not appear to confer any added benefit. There were no fetal deaths. The
      outcome for pregnancies where the mother presents with decreased fetal movements
      in the third trimester is comparable with the outcome for the general population.

PMID- 9650127
TI  - Quality assessment of two lactate test strip methods suitable for obstetric use.
AB  - Accuracy of lactate determinations in cord blood was tested for one
      reflectometric (Accusport) and one amperometric (Lactate Pro) microvolume test
      strip lactate meter. Both meters, using a whole blood sample, measure lower
      levels of lactate than a reflectometric device considered as a reference method,
      which analyses lactate in plasma. Readings were unaffected irrespective of
      lactate concentrations for the Lactate Pro, whilst the Accusport overestimated
      low lactate concentrations and underestimated high values. Both lactate meters
      underestimated lactate concentrations at high hematocrits, as compared with the
      reference method. The Lactate Pro has a fixed sample volume of 5 microliters
      while the Accusport uses random blood drop as sample volume. However, in analyses
      with less than 20 microliters sample volume considerable underestimation was
      found with the Accusport. Coefficient of variation was 3.8-8.9% for the Accusport
      and 3.1-4.0% for the Lactate Pro within lactate concentrations between 2.1 and
      5.3 mmol/l. The amperometric device, the Lactate Pro, performed best in these
      tests dealing with fetal blood lactate concentrations. The new technique can be a
      useful tool in perinatal research as well as in obstetric practice.

PMID- 9650128
TI  - Comparison of maternal and cord blood polymorphonuclear leukocyte elastase
      levels.
AB  - The main objective of this study was to examine the influence of parturition on
      the polymorphonuclear leukocyte elastase release in the fetus and the mother.
      There were 32 babies and parturients. The mean arterial cord blood elastase level
      was 294.8 +/- 129.15 ng/ml (median 304.25), while the mean plasma (venous) level
      in the adult normal controls was 35.66 +/- 14.1 ng/ml. The difference was highly
      significant at p < 0.0001 (Student's t test, two-tailed). The mean elastase level
      of the mothers was 143.45 +/- 109 ng/ml (median 115.25). This was significantly
      lower than the mean arterial cord blood elastase level (p < 0.0001) but higher
      than the mean elastase level in healthy adults (p < 0.0001). The mean cord blood
      and the mothers' white blood cell counts were 11.9 +/- 3.1 (median 11.8, range
      6.3-18.7 x 10(9)/l) and 12.4 +/- 2.8 (median 12.4, range 7.3-17.1 x 10(9)/l)
      respectively. The difference was not statistically significant (p = 0.4). The WBC
      counts correlated significantly with the mothers' (r = 0.4, p = 0.03) and cord
      blood (r = 0.7, p < 0.0001) elastase levels. These results suggest that the
      raised arterial cord blood elastase levels during parturition may reflect the
      disturbance of fetal homeostasis during parturition.

PMID- 9650129
TI  - Risk factors for neonatal sepsis in offspring of women with prelabor rupture of
      the membranes at 34-42 weeks.
AB  - One thousand three hundred eighty-five women with PROM (prelabor rupture of the
      membranes) participated in a prospective randomized study. Women with PROM were
      randomized to induction the following morning after PROM (early induction group)
      or induction two days later (late induction group). If contractions started
      within 2 hours after admission these women were included in the short latency
      group. All neonatal infections were classified as verified sepsis (positive
      culture) or clinical sepsis. The aim of the study was to compare the perinatal
      infectious outcome between the groups with different expectant managements in
      women with PROM and to study the association between demographic, intrapartum and
      postpartum variables and neonatal sepsis. In the short latency group one neonate
      had a proven sepsis while four neonates with proven sepsis were found in the
      early induction group. No proven sepsis was detected in the late induction group.
      Univariate analyses showed a significant association between clinical sepsis and:
      induction of labor (OR = 2.94, 95% CI 1.30-6.68), established labor 24.1-32 hours
      after ROM (OR = 5.89, 95% CI 1.68-20.63), established labor > 32 hours after ROM
      (OR = 4.59, 95% CI 1.52-13.87), time from ROM to delivery > 32 hours (OR = 5.07,
      95% CI 1.40-18.39), cesarean section (OR = 11.03, 95% CI 4.10-29.68),
      chorioamnionitis before or during delivery (OR = 27.14, 95% CI 2.38-309.16),
      endometritis (OR = 18.08, 95% CI 1.82-179.87), CRP over 20 mg/l in the umbilical
      cord (OR = 17.12, 95% CI 5.68-52.12) and Apgar score < 7 after 1, 5 or 10
      minutes. In a stepwise logistic regression analysis a significant association was
      found between clinical sepsis and cesarean section (OR = 10.08, 95% CI = 3.26
      31.20), time from ROM to delivery > 32 h (OR = 3.74, 95% CI 1.62-8.62),
      gestational age 34-36 weeks (OR = 3.16, 95% CI 1.11-8.96) and parous women (OR =
      2.41, 95% CI 1.04-5.57). In conclusion, this study indicates that that there was
      no difference in the incidence of neonatal infections between those with early
      and late induction. Clinical neonatal sepsis was associated with time from PROM
      to delivery over 32 hours, cesarean section, parous women and gestational age
      between 34 and 36 weeks.

PMID- 9650130
TI  - Computerised analysis of fetal heart rate recordings in patients with diabetes
      mellitus: the Dawes-Redman criteria may not be valid indicators of fetal well
      being.
AB  - Computerised cardiotocograph analysis has been used in our medical antenatal
      clinic for women with insulin dependent diabetes mellitus for five years. We had
      observed that many of the patients failed the computer criteria and wished to
      examine this finding in more detail. All cardiotocographs from 40 pregnant women
      with insulin dependent diabetes mellitus who delivered between 1992 and 1995 were
      reviewed. The number of traces failing the criteria were calculated. Outcome was
      compared between patients with a normal trace and those with an abnormal trace.
      233 recordings were examined. 30.5% of antenatal CTGs failed the criteria because
      of absent high episodes of variation (a parameter which is a specific marker of
      fetal well-being). After excluding repeat traces on all patients a sample of 26
      traces was examined. 34.6% of these had failed because of absent high episodes of
      variation. Both these figures are significantly higher than the published normal
      values. There was no apparent difference in neonatal outcome between women whose
      trace had failed (9) and those with a normal trace (17). We suggest that the
      normal values of criteria used to analyse computerised CTGs may not be valid when
      applied to fetuses of women with diabetes mellitus.

PMID- 9650131
TI  - Cerebral Doppler blood flow velocimetry and central hemodynamics in the ovine
      fetus during hypoxemia-acidemia.
AB  - The purpose of this study was to assess the effects of hypocapnic hypoxia,
      acidemia and the combination of hypoxia/acidemia on blood flow velocity variables
      in the fetal cerebral circulation. Chronically instrumented fetal sheep were used
      and the ewes were induced to breathe a hypoxic gas mixture for about 90 min. This
      caused an initial period of hypoxemia followed by a period of mixed
      hypoxemia/acidemia. When the ewe was reoxygenated, the fetus experienced a period
      of normoxic acidemia. The fetal cerebral circulation was assessed by recording
      Doppler blood flow velocity waveform variables in a cerebral vessel and the
      umbilical artery, using standard ultrasound equipment. External carotid artery
      blood flow was maintained during hypoxic and hypoxic/acidotic periods despite a
      fall in cardiac output. In the cerebral vessel, mean maximum velocity (time
      averaged maximum velocity), minimum diastolic velocity and maximum systolic
      velocity manifested increases during hypoxic and hypoxic-acidotic periods, but
      pulsatility index did not change due to the effect of reduced heart rate on
      pulsatility index. Umbilical artery pulsatility index increased in the hypoxic
      and hypoxic-acidotic periods, despite unchanged mean maximum velocity, minimum
      diastolic velocity and maximum systolic velocity. With acute hemodynamic changes,
      the measurement of pulsatility index can yield misleading results. For clinical
      and experimental research on the fetal cerebral circulation, more attention
      should be paid to the individual Doppler variables, especially to the mean
      maximum velocity, than to the pulsatility index alone. Changes in mean maximum
      velocity recorded from the cerebral artery seem to reflect changes in the
      cerebral arterial flow.

PMID- 9650132
TI  - Effects of magnesium sulfate infusion upon clotting parameters in patients with
      pre-eclampsia.
AB  - The objectives of this study were to evaluate the possible mechanisms involved in
      prolongation of bleeding time in pre-eclamptic patients receiving a magnesium
      sulfate infusion to prevent convulsions. Eighteen pre-eclamptic patients near
      term or at term (4 cases 33 to 35 weeks; the remainder > 36 weeks) were studied.
      Fifteen of them received magnesium sulfate infusion; 3 did not and served as
      controls. Bleeding time (modified Ivy method with Surgicutt), platelet count,
      platelet aggregation pattern, as well as serum arachidonic acid metabolites
      [thromboxane B2 (TxB2) and 6-Keto-prostaglandin F1 alpha (6-Keto-PGF1 alpha)]
      werde done on admission to the labor floor (before magnesium infusion) and
      repeated at discontinuation of the infusion, 12-24 hours postpartum; the controls
      received the second test 24 hours postpartum. Thirteen of 15 patients receiving
      magnesium sulfate had an increase in bleeding time from an average of 6 minutes
      31 seconds to 11 minutes 56 seconds, an 82% rise (p < 0.004). In 2 there was a
      decrease. Among the 3 controls the averages were 6 minutes 38 seconds and 6
      minutes 3 seconds. The total magnesium given ranged from 52.5 to 145 grams.
      Platelet counts averaged 251,000/mm3 (range 145,000-519,000). Platelet
      aggregation pattern done in 11 patients and was normal and unchanged after
      magnesium in 10 of the patients with increased bleeding time and one control.
      TxB2 and 6-Keto-PGF1 alpha levels did not change significantly either after
      magnesium administration (688 and 135 pgm/ml, to 654 and 117) or in controls (695
      and 230 pgm/ml, to 445 and 225). Likewise, the ratio of these 2 substances did
      not change in either group (6.3 to 6.6, and 4.2 to 2.2). There was no correlation
      between duration of infusion or total magnesium given and directions of small
      changes observed. This study confirms a prior preliminary observation that
      magnesium sulfate infusion, as currently used to prevent eclamptic convulsions,
      induces a significant prolongation of bleeding time. This effect is mediated
      neither by changes in platelets count or aggregation pattern, nor by changing the
      level or ratios of serum arachidonic acid metabolites (TxB2 and 6-Keto-PGF1
      alpha). Further studies are needed to clarify the mechanism of this clinically
      important observation of increased bleeding following magnesium sulfate infusion.

PMID- 9650133
TI  - The umbilical ring--the first rapid in the fetoplacental venous system.
AB  - In this study, the effect of the umbilical ring on blood flow velocities in the
      umbilical vein was examined using Doppler sonography. The maximum blood flow
      velocity in the umbilical vein was measured just before and behind the umbilical
      ring in eleven normal singleton pregnancies at 24-34 gestational weeks. The
      maximum velocity increased in each single case (p < 0.0001), the mean increase
      was from 16 cm/sec to 31 cm/sec. Thus, the narrowing of the umbilical ring serves
      as the first rapid in venous fetoplacental circulation. The physiological role of
      the acceleration of venous blood flow remains to be elucidated. Possible
      functions include stabilizing venous blood flow or preferential streaming.

PMID- 9650134
TI  - A simple technique to isolate DNA and supernatant of genital Mycoplasma hominis
      and Ureaplasma urealyticum.
AB  - Vaginal colonization with Mycoplasma hominis and Ureaplasma urealyticum has been
      implicated as a cause of prematurity. Several mechanisms to induce preterm labor
      have been discussed. The investigation of expressed and secreted enzymes requires
      a feasible method for culturing and further processing of these bacteria. We
      describe a simple technique for culturing of Mycoplasma hominis and Ureaplasma
      urealyticum without contamination with other microorganisms and isolating DNA and
      supernatant. PCR amplification of a chromosomal Mycoplasma fragment was performed
      as positive control.

PMID- 9650135
TI  - Cervical balloon for dysfunctional labor following amniotomy.
AB  - The conventional treatment for arrest of protracted active phase dilatation is
      amniotomy and oxitocin. This kind of labor dystocia is associated with an
      increased incidence in Cesarean delivery. We describe the use of cervical balloon
      after amniotomy for protracted active phase dilatation. We have used this
      approach in five parturients. All five patients had a spontaneous vaginal
      delivery. Intrapartum cervical balloon in patients with dysfunctional labor may
      reduce the need for Cesarean delivery.

PMID- 9650136
TI  - Effective drug treatment. Testing the distal needs hypothesis.
AB  - A long-standing view held by many drug abuse treatment providers, researchers,
      and policy makers is that maximally effective drug treatment needs to attend to
      the employment, health, housing, and other "distal needs" of the client. This
      paper tests the distal needs hypothesis by determining the effects of resolved,
      unresolved, and emergent family, housing, health, legal, emotional, and
      vocational needs on treatment engagement and treatment outcomes. Findings from a
      prospective, longitudinal study of 330 clients in 26 outpatient programs in the
      Los Angeles metropolitan area indicate little support for the distal needs
      hypothesis. Specifically, those with unresolved or emergent distal needs were not
      less likely to engage in treatment or use drugs during and after treatment.
      Treatment and research implications of these findings are addressed.

PMID- 9650137
TI  - The Teen Treatment Services Review (T-TSR).
AB  - This report describes the Teen-Treatment Services Review (T-TSR) and its initial
      testing. This brief interview modified from the adult Treatment Services Review
      (McLellan et al., 1992) furnishes a quantitative profile of the types and number
      of in-program and out-program treatment services provided during a treatment
      episode for substance use disorders (SUD). One-day test-retest interval data were
      collected from adolescent patients in a partial hospitalization program (PHP, N =
      20) and from an outpatient clinic (OPA, N = 24). The clinical utility is
      supported. The test-retest reliabilities of the T-TSR were variable. The T-TSR
      may be useful at the programmatic level in describing and comparing programs by
      the type and number of services delivered to adolescents with SUD. Additionally,
      it may offer a tool for quality assessment by evaluating actual patient treatment
      services matching. Further studies of the psychometric properties of this
      instrument in various clinical settings for adolescents are recommended.

PMID- 9650138
TI  - Measuring treatment process beliefs among staff of specialized addiction
      treatment services.
AB  - In a survey conducted in Ontario, front-line staff of specialized addiction
      treatment services were asked to indicate the extent to which they believed 53
      different treatment processes to be necessary for the effective treatment of
      people with alcohol and drug problems. Cognitive-behavioural processes were
      generally rated as almost essential for treatment to be effective. Other
      processes received mixed ratings, while confrontation and pharmacological
      treatment were, on average, rated as detrimental. Factor analysis identified
      three interpretable dimensions of beliefs (a) cognitive-behavioural, (b) disease,
      and (c) medication. A fourth dimension involved both psychodynamic and
      conditioning processes and did not clearly correspond with any known therapeutic
      approach. Scores on scales developed using items from these four dimensions were
      variously influenced by respondents age, education, place of work, and
      certification status. Two groups identified using cluster analysis differed
      primarily with respect to scores on the disease scale. Logistic regression
      analysis showed that age, certification status, and place of work were associated
      with membership in these groups. Implications for treatment system development
      and research are discussed.

PMID- 9650139
TI  - Smoking cessation for clients in chemical dependence treatment. A demonstration
      project.
AB  - A demonstration project was conducted to examine the factors that facilitate
      implementation of nicotine dependence treatment in a chemical dependence (cd)
      program. The project included: (a) staff education; (b) staff training to conduct
      nicotine dependence treatment groups; (c) voluntary smoking cessation treatment
      for smoking staff; and (d) smoking cessation treatment for client volunteers in
      outpatient and residential cd programs. A 12-week, cognitive/behavioral group
      program with nicotine patches was conducted separately for staff and client
      volunteers. Forty-two of approximately 70 staff returned smoking questionnaires,
      10 of whom reported current smoking. Four staff members began treatment, in
      addition to four staff from a second treatment agency. There were three of eight
      staff (37.5%) who reported ongoing abstinence at the end of the 12-week program.
      There were 83 cd clients (approximately 20% of smoking clients) who volunteered
      to participate in smoking cessation treatment. Forty clients began treatment, 3
      (7.5%) of whom were abstinent from smoking at the conclusion of the 12-week
      program. Staff smoking, lack of clinic resources devoted to the project, and
      voluntary client participation, which was adjunctive to other treatment
      components, were impediments to implementation and success. Success was greatest
      in a clinical setting in which smoking cessation treatment was staff supported
      and integrated with cd treatment. We recommend that (a) smoking cd staff be
      offered nicotine dependence treatment, (b) nicotine dependence treatment become a
      standard, integrated component of cd treatment, and (c) initiation of smoking
      cessation be individualized according to clients' needs and circumstances.

PMID- 9650140
TI  - Types of abuse and cocaine use in pregnant women.
AB  - Previous research has found an association between childhood and adult physical
      and sexual abuse and substance abuse, but has not examined or compared specific
      dimensions of the abuse experience, such as its age of onset or the type,
      severity, or frequency. Women receiving perinatal care (N = 1189) at an inner
      city hospital clinic were systematically questioned about their lifetime and
      current cocaine use and experiences of abuse. We found an association between a
      history of abuse in childhood and lifetime and current cocaine use, as well as
      physical and sexual abuse during childhood and pregnancy. There was no difference
      in the rates of cocaine use between women whose onset of abuse was in childhood
      versus adulthood. Childhood sexual abuse (alone or in combination with physical
      abuse) was more associated with lifetime cocaine use than was physical abuse
      alone. Cocaine use was related to the severity, but not the frequency of abuse.

PMID- 9650141
TI  - Stories of spiritual awakening. The nature of spirituality in recovery.
AB  - Substance abuse has had a devastating impact on the lives of millions. As
      substance use and abuse continues to ravage communities, researchers remain in
      the dark about what works to ensure successful recovery from addiction. In
      searching for the answers, researchers have often overlooked the role of
      religious and spiritual practices and beliefs in preventing use and relapse. The
      study reported here describes the process of spiritual awakenings experienced by
      some persons in recovery during their quest for sobriety. The data suggests that
      persons in recovery often undergo life altering transformations as a result of
      embracing a power higher than one's self, that is, a Higher Power. The result is
      often an intense spiritual journey that leads to sustained abstinence. Given how
      widespread substance abuse is, research on the nature, implications, and
      limitations of a spiritual approach to addiction might offer new options for
      treatment.

PMID- 9650142
TI  - The ARISE Intervention. Using family and network links to engage addicted persons
      in treatment.
AB  - An alternative method to the Johnson Institute's "Intervention" is presented
      which, while incorporating many of Johnson's innovations, is, additionally: (a)
      less confrontative, thereby avoiding the reactivity in clients and family members
      that such confrontational approaches have tended to evoke; (b) takes into account
      both the needs of the chemically dependent person as well as the needs of the
      larger family and network system; and (c) aimed toward enrolling substance
      abusers in outpatient (as well as inpatient) treatment, thus placing it more in
      line with managed care priorities. Principles for treatment engagement are
      presented, accompanied by case examples. The approach is part of a more
      comprehensive model designed to maximize successful engagement with a minimum
      amount of professional time and effort.

PMID- 9650143
TI  - Perceptions of the supervisory relationship. A preliminary qualitative study of
      recovering and nonrecovering substance abuse counselors.
AB  - Interviews with a sample (N = 5) of substance abuse counselors were conducted
      concerning perceptions of their relationship with their clinical supervisors. The
      interview protocol was developed from four existing supervision relationship
      inventories, with an additional group of questions concerning satisfaction with
      supervision. Significant themes were determined from the examination of interview
      data. In addition, the supervisory relationship responses were compared to
      responses about supervisee satisfaction with supervision. Salient themes also
      were compared based upon counselor and supervisor substance abuse recovery
      status. The significance of recovery within the supervisory relationship is
      discussed as well.

PMID- 9650144
TI  - Suicide attempts, substance abuse, and personality.
AB  - The prevalence and relevance of a positive suicide attempt history among 103
      subjects who had entered a substance abuse program and participated in a study of
      personality was examined. Twenty subjects had a positive suicide attempt history.
      Women were more likely to attempt suicide. Attempters were more likely to have
      additional psychiatric diagnoses, such as major depression. Attempters had higher
      addiction severity scores, abused more substances, and were more likely to have
      abused alcohol and sedative hypnotics than were nonattempters. DSM-III-R and
      Eysenck personality measures were compared across groups. Attempters had
      significantly higher neuroticism and borderline scores. Impulse dysregulation may
      predispose this group to more severe addictions.

PMID- 9650145
TI  - A review of systematic and quantifiable methods of estimating the needs of a
      community for alcohol treatment services.
AB  - The purpose of this paper was to review a variety of systematic and quantifiable
      methodologies for planning and evaluating the provision of alcohol treatment
      services for communities. These methods include: (a) developing and evaluating
      indicators of alcohol-related harm in and across defined geographic areas, to
      assess the relative need for services; (b) demand-oriented techniques that
      involve the prediction of future demand for services based on the previous
      utilisation of treatment facilities; (c) comprehensive systems approaches to
      planning services; and (d) the estimation of the prevalence of individuals who
      need or would benefit from an intervention for their alcohol problem. In
      practice, service planners may incorporate a combination of approaches that could
      be compared and contrasted to assess the convergent validity of results. These
      methodologies can also be used to provide information for planning and evaluating
      prevention/health promotion and early intervention initiatives.

PMID- 9650146
TI  - Accountability in public short-term adult AOD residential treatment.
      Fontainebleau Treatment Center.
AB  - Fontainebleau Treatment Center provides short-term public residential AOD
      treatment and primary health care to a lower-socioeconomic adult population. The
      multimodal focus of treatment includes interactive group therapy, behavioral
      contracting, relapse prevention, and 12-step involvement. Research funded by the
      National Institute on Drug Abuse indicated both positive treatment outcome and
      significant cost efficacy. These results may be in some contrast to prevailing
      assumptions about public sector, government-operated behavioral health-care
      delivery to high-risk populations. Multiple variables for consideration in future
      outcome research are discussed, with potential for database inclusion toward
      standardization of treatment and cost protocols.

PMID- 9650147
TI  - Shouting 'cure!'--or whispering 'hope'--in a crowded cancer ward.

PMID- 9650148
TI  - Research funding and cloning: top recent policy agenda.

PMID- 9650149
TI  - Promoting the health and wellness of women with disabilities.

PMID- 9650150
TI  - Pamphlets for your patients: diabetes.

PMID- 9650151
TI  - Toward optimal health: the experts discuss tamoxifen and breast cancer
      prevention. Interview by Jodi Godfrey Meisler.

PMID- 9650152
TI  - Soy: just a hill of beans?

PMID- 9650153
TI  - A review of the effectiveness of Cimicifuga racemosa (black cohosh) for the
      symptoms of menopause.
AB  - In this review of eight human studies on the effectiveness of an extract of
      Cimicifuga racemosa on alleviating menopausal symptoms, it is apparent that it is
      a safe, effective alternative to estrogen replacement therapy for those patients
      in whom estrogen replacement therapy is either refused or contraindicated.

PMID- 9650155
TI  - Female gender as a risk factor for drug-induced cardiac arrhythmias: evaluation
      of clinical and experimental evidence.
AB  - One of the most pronounced gender-based differences in response to drugs is
      women's far greater risk of developing the life-threatening ventricular
      arrhythmia called torsades de pointes (TdP). A review of the literature and
      databases of the Food and Drug Administration reveals that a much higher
      percentage of women than men develop TdP arrhythmias after taking a variety of
      drugs, such as antihistamines (terfenadine, astemizole), antibiotics
      (erythromycin), antimalarials (halofantrine), antiarrhythmics (quinidine, d
      sotalol), and miscellaneous other drugs. All of these drugs have in common the
      ability to block potassium currents, thereby prolonging cardiac repolarization
      and the QT interval on the ECG. The available experimental data support the
      hypothesis that gender differences in specific cardiac ion current densities are
      responsible, at least in part, for the greater susceptibility of females for
      developing TdP arrhythmias. In isolated perfused rabbit hearts (Langendorff
      technique), female rabbit hearts display greater baseline and drug-induced
      (quinidine and d-sotalol) changes in QT intervals than male hearts, and at least
      two different repolarizing potassium current densities (IKr and IKl) are found to
      be significantly lower in ventricular cardiomyocytes from female rabbits compared
      with those from males. Thus, it appears that as in humans, clear gender
      differences exist in the electrophysiologic characteristics governing cardiac
      repolarization in rabbits. This model and perhaps others should be examined as
      predictors of functional and pharmacologic differences between men and women.
      Understanding the potential mechanisms responsible for the greater risk of drug
      induced arrhythmias in women could lead to screening methods for identification
      of individuals at risk for drug-induced arrhythmias or to the development of
      drugs with reduced risk of inducing arrhythmia.

PMID- 9650154
TI  - Genetic testing for BRCA1 and BRCA2: recommendations of the Stanford Program in
      Genomics, Ethics, and Society. Breast Cancer Working Group.

PMID- 9650156
TI  - Menopause: when hormone replacement therapy is not an option. Part I.
AB  - Although the perimenopausal period is often experienced as a positive life
      transition, it is frequently accompanied by a variety of distressing physical and
      emotional sequelae. Hormone replacement therapy (HRT) has been hailed as the
      first-line treatment for many of these symptoms. A significant number of women,
      however, are unable to take exogenous hormones because of absolute or relative
      contraindications to therapy. Other women are unwilling to use this treatment for
      a variety of reasons, including reluctance to use unnatural exogenous hormones
      and fear of unknown risks of HRT. This two-part review discusses the physiology
      of menopause and its related symptoms, as well as the risks and benefits of both
      oral and non-oral routes of hormone administration. Self-help measures and
      alternative therapeutic options are recommended for the treatment of menopausal
      symptoms, which include vasomotor instability, urogenital atrophy, psychologic
      disturbances, and risk of osteoporosis and cardiovascular disease.

PMID- 9650157
TI  - Compromised bone density 11.4 years after diagnosis of anorexia nervosa.
AB  - This investigation evaluated bone density in 36 premenopausal women (mean +/- SD
      age = 29.5 +/- 8.4 years) an average of 11.4 years after diagnosis for anorexia
      nervosa. Twenty-nine women were aged 20-45 years, and seven were aged 16-19
      years. Body composition, age of menarche, length of amenorrhea, estrogen
      exposure, and lumbar spine and proximal femur bone density were determined.
      Average appendicular bone density for those > or = 20 years was found to meet
      World Health Organization T score criteria for osteopenia: total femur T = -1.22
      and femoral neck T = -1.33. The average total lumbar Z score for all 36
      participants was -0.95, which was 90% of the mean for their age, and the mean Z
      scores for adolescent subjects were within 91% of the mean for their age (Z = 
      0.84). Years of estrogen exposure were correlated with lumbar mineral content (r
      = 0.50, p = 0.002). A modest but significant inverse relationship was observed
      between length of amenorrhea and femoral and lumbar bone density. The total
      proximal femur and trochanteric bone densities were best predicted, using
      stepwise regression, by the number of years after diagnosis and years of
      amenorrhea, respectively (R2 = 0.23, p = 0.02 and R2 = 0.21, p = 0.04). Lumbar
      density was best predicted by years of amenorrhea and current percent of ideal
      body weight (%IBW)(R2 = 0.25, p = 0.02). Length of amenorrhea, estrogen exposure,
      and %IBW independently contribute to axial and appendicular bone density. Because
      of risk for compromised bone density, women with a history of anorexia nervosa
      should be followed longitudinally to maximize premenopausal bone replacement.

PMID- 9650158
TI  - Impairment of autonomic function induced by posture change in postmenopausal
      women.
AB  - This study was designed to determine if there is a difference in autonomic
      regulation induced by posture change between postmenopausal and young women. To
      evaluate autonomic nervous system function, spectral analysis of heart rate
      variability (HRV) was done in postmenopausal women (n = 13, 46-59 years of age),
      age-matched men (n = 8, 45-55 years of age), and young women (n = 10, 20-37 years
      of age) for 3-min periods of controlled frequency breathing (15 breaths/min) in
      supine followed by sitting positions. In the supine position, the R-R interval
      variation in older persons decreased significantly compared with that during the
      follicular phase in young women. Furthermore, the high-frequency (HF) components
      of HRV, which reflect only parasympathetic activity, were lower in older subjects
      than in young women. Following a change of position from supine to sitting, the
      HF component did not change significantly in the postmenopausal women or the men,
      but the low/high frequency (LF/HF) component ratio, which reflects the balance of
      autonomic nerve activities, increased significantly in the men. These results
      suggest that cardiac parasympathetic tone may be reduced in older persons in
      comparison with young women. Furthermore, arterial baroreflex control of
      parasympathetic nerve activity caused by posture changes is impaired in the
      postmenopausal women and aged-matched men. The baroreflex control of the
      sympathetic component is maintained in the men but not in the postmenopausal
      women. These differences might result in part from changes in the level of female
      hormones.

PMID- 9650159
TI  - Stress urinary incontinence in women: guidelines for surgical treatment.

PMID- 9650160
TI  - Preventing HIV infection: the effects of community linkages, time, and money on
      recruiting and retaining women in intervention groups.
AB  - Few studies have addressed recruitment and retention of participants in
      preventive interventions directed at human immunodeficiency virus (HIV), and
      these generally have not focused on women. In this study, part of the Women in
      Group Support (WINGS) project, we examine the experience of three sites in
      recruiting 444 high-risk women for a small group intervention to reduce risky
      sexual behavior. The intervention included six structured sessions, followed by a
      continuing series of client-focused, drop-in sessions. Incentives for
      participants included child care, food, and transportation tokens. Attendees at
      each structured session also received a cash incentive of $10-$20. Forty-six
      percent of the women were recruited from community sources, 35% from clinics, and
      19% from drug programs. Across all recruitment sources, almost a third of the
      women reported having had a sexually transmitted disease (STD) in the past year,
      88%-94% reported a risky male partner (who, they believed, had sex with other
      partners or with sex workers, was an injecting drug user, or was HIV positive),
      and 10%-36% reported trading sex for money or drugs. During 18 months of
      recruitment, each site averaged 34 screening interviews monthly to secure 8
      eligible women a month who completed baseline interviews and reported for
      randomization. The average number of paid sessions attended by participants was
      five of six (83%). Average attendance at unpaid sessions was 1 of 12 (8%). Key
      facilitators to recruitment and retention included linkages with community
      agencies and monetary incentives. Our findings suggest that researchers and
      community service providers need to explore alternative strategies to paying
      women for attending group sessions (e.g., incorporating group interventions into
      existing program requirements) and balance these against the costs and
      recruitment effectiveness.

PMID- 9650161
TI  - Women as caregivers.

PMID- 9650162
TI  - Anxiety and depression. Diagnosis and treatment during pregnancy.

PMID- 9650163
TI  - Specificity of neurobehavioral outcomes associated with prenatal alcohol
      exposure.

PMID- 9650164
TI  - National Institutes of Health Consensus Development Conference statement on
      cervical cancer. April 1-3, 1996.

PMID- 9650165
TI  - LiteratureWatch.

PMID- 9650166
TI  - 1st Vitreoretinal Symposium. March 20th and 21st, 1998 in Frankfurt am Main.

PMID- 9650167
TI  - Proposition: federally mandated imaging standards (e.g., MQSA) serve the best
      interests of patients.

PMID- 9650168
TI  - Preliminary study of a metal/a-Se-based portal detector.
AB  - A feasibility study has been performed on metal/amorphous selenium detectors for
      megavoltage portal imaging. The metal plates of the detectors were positioned
      facing the incident 6 MV and Co-60 photon spectra. The detectors consist of
      various thicknesses (0.15 mm, 0.30 mm, and 0.50 mm) of amorphous selenium (a-Se)
      deposited on metal plates of varying thicknesses: aluminum (2.0 mm), copper (1.0
      mm and 1.5 mm), stainless steel (0.9 mm), or glass (1.1 mm). The detectors were
      charged prior to irradiation by corona methods, and the portal images were
      subsequently digitized after irradiation with a noncontact electrostatic probe.
      The sensitivity of the detectors to dose, electric field across the a-Se layer,
      metal plate type and a-Se thickness, was studied. The electrostatic voltage
      remaining on the a-Se layer was found, both theoretically and experimentally, to
      exhibit a cubic relationship with respect to dose. An increase in electric field
      increases the sensitivity (gradient of the a-Se surface voltage vs dose curve)
      and dynamic range of the resultant image. An increase in a-Se thickness, however,
      although also increasing the sensitivity, decreases the dynamic range. The metal
      plate types and thicknesses within the range studied do not have a significant
      effect on detector sensitivity. Image quality and contrast resolution of the
      detector were evaluated with a contrast-detail phantom and compared to
      commercially available film based and electronic portal imaging devices. Image
      quality of the metal/a-Se detector as a function of dose was studied by
      discharging the a-Se to various fractions of its initial charge, and as expected,
      increases with dose due to a decrease in quantum noise. Contrast-detail images
      obtained by metal/a-Se detectors are superior to those obtained at higher dose
      levels by other commercial systems.

PMID- 9650169
TI  - A simple algorithm for planar image registration in radiation therapy.
AB  - A simple algorithm is presented for planar image registration and the method is
      applied to the simulator and portal image registration for patient setup
      verification in radiation therapy. Basically, the algorithm follows the concept
      proposed by Balter et al. [Med. Phys. 19, 329-334 (1992)], which converts the
      problem of open curve registration into matching a series of points along the
      curves. Balter's algorithm consists of three steps: (1) to determine a common
      starting point for each curve pair, (2) acquire two corresponding point sets
      along each curve, and (3) obtain a global transform matrix by matching two point
      sets. We integrate all three steps into one simple procedure which fits the
      sampled points along the intended curve pair by taking the relative path length
      shift as an independent fitting parameter. After being modified, the algorithm is
      able to take the different magnification factors of images into account, and it
      avoids curvature calculations. Numerical simulation as well as clinical and
      phantom images have been utilized to test the accuracy of the algorithm. The
      typical errors are less than 1 mm in translation and 1 degree in rotation. We
      also made a comparison study with the chamfer method. The results of the two
      methods agree to within 0.5 mm in translation and 0.5 degree in rotation.

PMID- 9650170
TI  - Portal dose image (PDI) prediction for dosimetric treatment verification in
      radiotherapy. I. An algorithm for open beams.
AB  - A method is presented for calculation of transmission functions for high energy
      photon beams through patients. These functions are being used in our clinic for
      prediction of portal dose images (PDIs) which are compared with PDIs measured
      with an electronic portal imaging device (EPID). The calculations are based on
      the planning CT-scan of the patient and on the irradiation geometry as determined
      in the treatment planning process. For each beam quality, the required input data
      for the algorithm for transmission prediction are derived from a limited number
      of measured beam data. The method has been tested for a PDI-plane at 160 cm from
      the focus, in agreement with the fixed focus-to-detector distance of our
      fluoroscopic EPIDs. For 6, 23 and 25 MV photon beams good agreement
      (approximately 1%) has been found between calculated and measured transmissions
      through anthropomorphic phantoms.

PMID- 9650171
TI  - A pencil-beam photon dose algorithm for stereotactic radiosurgery using a
      miniature multileaf collimator.
AB  - A computer-controlled miniature multileaf collimator (MMLC) with 4 mm leaf width
      and a maximum field size of 6 cm X 6 cm has been designed as a tertiary beam
      shaping device for linac-based stereotactic radiosurgery. The purpose of this
      study is to develop an accurate and efficient dose calculation model for use with
      the MMLC. A pencil-beam based algorithm using a sum of three Gaussian kernels was
      developed to model the off-axis ratio of MMLC fields. Because the kernel
      integration over a rectangular field can be solved in closed form, dose to any
      point from an arbitrary MMLC field can be calculated efficiently by summing dose
      contribution from a set of rectangular apertures and transmission blocks that
      model individual leaf openings or leaf transmissions. The model uses an effective
      rectangular field and equivalent square method for determination of depth dose
      and dose output. Results showed that the calculated percentage depth dose was
      within 1% and output factor was within 1.5% of measured data. The parameters of
      the pencil beam kernels were extracted by fitting measured off-axis profiles for
      a few field sizes at a few depths. The accuracy of the calculated off-axis ratio
      was tested by comparison with measured data for a number of MMLC fields. The
      algorithm was shown to be accurate to within 1.5% or 1 mm for off-axis ratios.
      The algorithm computes at a speed of 34,600 data points per second on a DEC Alpha
      server model 2000/433 (Digital Equipment Corp., Maynard, MA), which is about 15
      times faster than a Clarkson-type summation method.

PMID- 9650172
TI  - Multiple scattering theory for total skin electron beam design.
AB  - The purpose of this manuscript is to describe a method for designing a broad beam
      of electrons suitable for total skin electron irradiation (TSEI). A theoretical
      model of a TSEI beam from a linear accelerator with a dual scattering system has
      been developed. The model uses Fermi-Eyges theory to predict the planar fluence
      of the electron beam after it has passed through various materials between the
      source and the treatment plane, which includes scattering foils, monitor chamber,
      air, and a plastic diffusing plate. Unique to this model is its accounting for
      removal of the tails of the electron beam profile as it passes through the
      primary x-ray jaws. A method for calculating the planar fluence profile for an
      obliquely incident beam is also described. Off-axis beam profiles and percentage
      depth doses are measured with ion chambers, film, and thermoluminescent
      dosimeters (TLD). The measured data show that the theoretical model can
      accurately predict beam energy and planar fluence of the electron beam at normal
      and oblique incidence. The agreement at oblique angles is not quite as good but
      is sufficiently accurate to be of predictive value when deciding on the optimal
      angles for the clinical TSEI beams. The advantage of our calculational approach
      for designing a TSEI beam is that many different beam configurations can be
      tested without having to perform time-consuming measurements. Suboptimal
      configurations can be quickly dismissed, and the predicted optimal solution
      should be very close to satisfying the clinical specifications.

PMID- 9650173
TI  - Photon beam skin dose analyses for different clinical setups.
AB  - A comprehensive set of data on skin dose for 8 MV and 18 MV photon beams from a
      medical linear accelerator was measured using a parallel-plate chamber to
      document the effect of field size, source-to-surface distance (SSD), off-axis
      distance, acrylic block tray, wedge (external standard wedge), Lipowitz's metal
      block, multileaf collimator (MLC), and dynamic wedge. The skin dose increased as
      field size increased from 5 X 5 cm2 to 40 X 40 cm2 (6% to 38% for 8 MV and 5% to
      44% for 18 MV beam). With the use of an acrylic block tray, the skin dose
      increased for all field sizes (7% to 59% for 8 MV and 5% to 62% for 18 MV beam),
      but the increase was minimal for small fields. The skin dose with a wedge showed
      a much more complex trend. It was generally lower than the dose for an open
      field, but higher in the case of large fields and higher degree wedges. When both
      wedge and block tray were used, the tray was a major contributor to the skin dose
      because some of the contaminant electrons from the wedge assembly were absorbed
      by the block tray. Field-shaping blocks increased the skin dose, but,
      interestingly, the block tray reduced the skin dose for small blocked fields
      treated with a high-energy photon beam. The effect of an MLC on skin dose was
      very similar to that of a Lipowitz's metal block, but its magnitude was less. The
      skin dose was higher for dynamic wedge fields than it was for standard wedge
      fields. As SSD decreased, the skin dose increased, and this effect was dominant
      in larger field sizes. The SSD effect was enhanced in the presence of an acrylic
      block tray. The skin dose off-axis was the same as at the central axis, or
      smaller. A similar pattern of behavior of the skin dose is expected for photon
      beams from other linear accelerators.

PMID- 9650174
TI  - A patient-specific Monte Carlo dose-calculation method for photon beams.
AB  - A patient-specific, CT-based, Monte Carlo dose-calculation method for photon
      beams has been developed to correctly account for inhomogeneity in the patient.
      The method employs the EGS4 system to sample the interaction of radiation in the
      medium. CT images are used to describe the patient geometry and to determine the
      density and atomic number in each voxel. The user code (MCPAT) provides the data
      describing the incident beams, and performs geometry checking and energy scoring
      in patient CT images. Several variance reduction techniques have been implemented
      to improve the computation efficiency. The method was verified with measured data
      and other calculations, both in homogeneous and inhomogeneous media. The method
      was also applied to a lung treatment, where significant differences in dose
      distributions, especially in the low-density region, were observed when compared
      with the results using an equivalent pathlength method. Comparison of the DVHs
      showed that the Monte Carlo calculated plan predicted an underdose of nearly 20%
      to the target, while the maximum doses to the cord and the heart were increased
      by 25% and 33%, respectively. These results suggested that the Monte Carlo method
      may have an impact on treatment designs, and also that it can be used as a
      benchmark to assess the accuracy of other dose calculation algorithms. The
      computation time for the lung case employing five 15-MV wedged beams, with an
      approximate field size of 13 X 13 cm and the dose grid size of 0.375 cm, was less
      than 14 h on a 175-MHz computer with a standard deviation of 1.5% in the high
      dose region.

PMID- 9650175
TI  - Beam profiles for x-ray rotation therapy.
AB  - Determining the beam configuration necessary to deliver a desired dose
      distribution with rotation therapy is equivalent to solving an integral equation.
      The equation has been solved analytically for a handful of dose distributions
      having specific radial variation and either rotational or reflective angular
      symmetry. In this work a numerical method for calculating beam profiles
      appropriate for producing distributions having arbitrary radial variation and
      angular symmetry of order l > or = 2 is presented. The accuracy of the technique
      is demonstrated by comparison with one of the few dose distributions for which an
      analytic solution exists, and the ability to produce both more general and
      conformal distributions is also shown. The problems of negative intensity and
      scatter are discussed.

PMID- 9650176
TI  - Combined use of FLUKA and MCNP-4A for the Monte Carlo simulation of the dosimetry
      of 10B neutron capture enhancement of fast neutron irradiations.
AB  - Boron neutron capture enhancement (BNCE) of the fast neutron irradiations use
      thermal neutrons produced in depth of the tissues to generate neutron capture
      reactions on 10B within tumor cells. The dose enhancement is correlated to the
      10B concentration and to thermal neutron flux measured in the depth of the
      tissues, and in this paper we demonstrate the feasibility of Monte Carlo
      simulation to study the dosimetry of BNCE. The charged particle FLUKA code has
      been used to calculate the primary neutron yield from the beryllium target, while
      MCNP-4A has been used for the transport of these neutrons in the geometry of the
      Biomedical Cyclotron of Nice. The fast neutron spectrum and dose deposition, the
      thermal flux and thermal neutron spectrum in depth of a Plexiglas phantom has
      been calculated. The thermal neutron flux has been compared with experimental
      results determined with calibrated thermoluminescent dosimeters (TLD-600 and TLD
      700, respectively, doped with 6Li or 7Li). The theoretical results were in good
      agreement with the experimental results: the thermal neutron flux was calculated
      at 10.3 X 10(6) n/cm2 s1 and measured at 9.42 X 10(6) n/cm2 s1 at 4 cm depth of
      the phantom and with a 10 cm X 10 cm irradiation field. For fast neutron dose
      deposition the calculated and experimental curves have the same slope but
      different shape: only the experimental curve shows a maximum at 2.27 cm depth
      corresponding to the build-up. The difference is due to the Monte Carlo
      simulation which does not follow the secondary particles. Finally, a dose
      enhancement of, respectively, 4.6% and 10.4% are found for 10 cm X 10 cm or 20 cm
      X 20 cm fields, provided that 100 micrograms/g of 10B is loaded in the tissues.
      It is anticipated that this calculation method may be used to improve BNCE of
      fast neutron irradiations through collimation modifications.

PMID- 9650177
TI  - A light localizer for use at large distances from a radiation source.
AB  - In the superconducting cyclotron used for neutron therapy at Harper Hospital,
      space limitations prevented the use of a simple conventional light localizing
      system, employing a single mirror and a light source. The superconducting magnet
      coil is close to the neutron producing target and the vacuum window separating
      the acceleration chamber from atmospheric pressure is situated approximately 56
      cm from this target. Therefore, the light localizing system must be designed to
      incorporate lenses, mirrors, an optical fiber light pipe and adjustment motors,
      in order to make the system compact enough to fit in the available space and to
      allow easy access for adjustment and alignment. The design of the light
      localizing system is explained in detail.

PMID- 9650178
TI  - A practical target system for accelerator-based BNCT which may effectively double
      the dose rate.
AB  - A dose-limiting component of a proton accelerator-based source of epithermal
      neutrons is the neutron production target. Possible targets are lithium,
      producing high yield but having low melting point and thermal conductivity, and
      beryllium, presenting less engineering problems but a much smaller neutron yield.
      We propose that a hybrid Be-Li target would provide the best of both worlds, with
      the upstream beryllium component producing neutrons and providing containment to
      the lithium, and the downstream liquid lithium in turn producing further neutrons
      as well as cooling the beryllium. The engineering considerations associated with
      such a target system are within the range of current technology. Calculations
      suggest a yield of such a practical target that is at least double that from pure
      beryllium.

PMID- 9650179
TI  - Microprocessor controlled limitation system for a stand-alone freely movable
      treatment couch.
AB  - Because of the capability of free movement in the treatment room, we recently
      introduced a Hercules treatment couch on one of our linear accelerators. One of
      the advantages of this couch is that it allows for a more flexible way of patient
      setup and that it can be moved entirely out of the way to enable treatment with a
      hospital bed. A disadvantage, however, is that the couch can hit a wall or a
      cover of the accelerator accidentally. A limitation system has been developed to
      protect both the table and the accelerator against such collisions.

PMID- 9650180
TI  - Liquid ionization chambers for absorbed dose measurements in water at low dose
      rates and intermediate photon energies.
AB  - Two new liquid ionization chamber (LIC) designs, consisting of cylindrical and
      plane-parallel configurations, are presented. They are designed to be suitable
      for high-precision measurements of absorbed dose-to-water at dose rates and
      photon energies typical for LDR intermediate photon energy brachytherapy sources.
      The chambers have a sensitive liquid layer thickness of 1 mm and sensitive
      volumes of 7 mm3 (plane-parallel) and 20 mm3 (cylindrical). The liquids used as
      sensitive media in the chambers are either isooctane (C8H18), tetramethylsilane
      (Si(CH3)4) or mixtures of these two liquids in the approximate proportions 2 to
      1. A chamber filled with such a liquid mixture and with a polarizing voltage of
      300 V, provides a volume sensitivity of about 10(-9)C Gy(-1) mm(-3) for absorbed
      dose measurements in water in an x-ray radiation field with an effective photon
      energy of 120 keV. In the interval 30 to 140 keV, the relative change in
      sensitivity is less than +/- 2.5%. The leakage current of the chambers is low and
      stable, which implies that absorbed dose measurements can be done with good
      reproducibility at dose-rates as low as 50 microGy min-1 (sigma < 3%). The long
      term calibration stability was tested for a set of five chambers over a period of
      more than 1 year. No systematic change in their sensitivity could be observed.
      The general recombination at a polarizing voltage of 300 V is less than 2% for
      dose-rates up to about 100 mGy min-1. The temperature dependence at room
      temperature is 0.5% per degree C. The response is almost independent of the
      direction of the radiation for the plane-parallel LIC.

PMID- 9650181
TI  - Determination of saturation charge and collection efficiency for ionization
      chambers in continuous beams.
AB  - The procedure recommended by radiation dosimetry protocols for determining the
      collection efficiency f of an ionization chamber assumes the predominance of
      general recombination and ignores other charge loss mechanisms such as initial
      recombination and ionic diffusion. For continuous radiation beams, general
      recombination theory predicts that f can be determined from a linear relationship
      between 1/Q and 1/V2 in the near saturation region (f > 0.7), where Q is the
      measured charge and V the applied chamber potential. Measurements with Farmer
      type cylindrical ionization chambers exposed to cobalt-60 gamma rays reveal that
      the assumed linear relationship between 1/Q and 1/V2 breaks down in the extreme
      near-saturation region (f > 0.99) where Q increases with V at a rate exceeding
      the predictions of general recombination theory. A comprehensive model is
      developed to describe the saturation characteristics of ionization chambers. The
      model accounts for dosimetric charge loss (initial recombination, ionic
      diffusion, and general recombination) and nondosimetric charge multiplication in
      an ionization chamber, and suggests that charge multiplication plays a
      significant role under typical chamber operating conditions (300 V) used in
      radiation dosimetry. Through exclusion of charge multiplication from the measured
      chamber signal Q, the model predicts the breakdown of the 1/Q vs 1/V2
      relationship and shows that the final approach to saturation is governed by
      initial recombination and ionic diffusion which are characterized by a linear
      relationship between 1/Q and 1/V. Collection efficiencies calculated with this
      model differ by up to 0.4% from those determined through a rigorous application
      of general recombination theory alone.

PMID- 9650182
TI  - Influence of electron contamination on in vivo surface dosimetry for high-energy
      photon beams.
AB  - The influence of the electron contamination at in vivo dosimetry with diodes on
      the patient surface has been investigated by introducing different accessories in
      the beam path and by changing the field size and SSD. The results show a clear
      correlation between the electron contamination at an effective measuring depth of
      the diode and the signal from the patient diode. When the electron contamination
      is taken into account the agreement between the diode values and the absorbed
      dose is greatly improved. More accurate in vivo dosimetry with less error margins
      is therefore possible if better predictions of the electron contamination in high
      energy photon beams can be performed.

PMID- 9650183
TI  - Texture analysis in radiographs: the influence of modulation transfer function
      and noise on the discriminative ability of texture features.
AB  - Tissue structures, represented by textures in radiographs, can be quantified
      using texture analysis methods. Different texture analysis methods have been used
      to discriminate between different aspects of various diseases in primarily x rays
      of chest, bone, and breasts. However, most of these methods have not specifically
      been developed for use on radiographs. Certain characteristics of the
      radiographic process, e.g., noise and blurring, influence the visible texture. In
      order for a texture analysis method to be able to discriminate between different
      underlying textures, it should not be too sensitive for such processes as image
      noise and blur. In this study, we investigated the sensitivity of four different
      texture analysis methods for image noise and blur. First, a baseline measurement
      was performed of the discriminative performance of the Spatial Gray-Level
      Dependence method, the Fourier Power Spectrum, the Fractal Dimension, and the
      Morphological Gradient Method on images, which were not affected by radiographic
      noise and blur. Two types of images were used: fractal and Brodatz. Whereas the
      Brodatz images represent very different textures, the differences between the
      fractal images are more gradual. We assume that the behavior of the different
      texture analysis methods on the fractal images is representative for their
      performance on radiologic textures. On these types of images we simulated the
      effect of four different noise levels and the effect of two different modulation
      transfer functions, corresponding with different screenfilm combinations. The
      influence on the discriminative performance of the four texture analysis methods
      was evaluated. The influence of noise on the discriminative performance is, as
      expected, dependent on the image type used; the discrimination of more gradually
      different images, such as the fractal images, is already lowered for relatively
      low noise levels. In contrast, when the images are more different, only high
      noise levels decrease the discriminative performance. The discriminative power of
      the Morphological Gradient Method is least affected by image blur. We conclude
      that the discriminative performance of the Morphological Gradient Method is
      superior to that of other methods in circumstances which mimic the conditions
      prevailing in radiographs.

PMID- 9650184
TI  - Classification of compressed breast shapes for the design of equalization filters
      in x-ray mammography.
AB  - We are developing an external filter method for equalizing the x-ray exposure in
      mammography. Each filter is specially designed to match the shape of the
      compressed breast border and to preferentially attenuate the x-ray beam in the
      peripheral region of the breast. To be practical, this method should require the
      use of only a limited number of custom built filters. It is hypothesized that
      this would be possible if compressed breasts can be classified into a finite
      number of shapes. A study was performed to determine the number of shapes. Based
      on the parabolic appearance of the outer borders of compressed breasts in
      mammograms, the borders were fit with the polynomial equations y = ax2 + bx3 and
      y = ax2 + bx3 + cx4. The goodness-of-fit of these equations was compared. The a,b
      and a,b,c coefficients were employed in a K-Means clustering procedure to
      classify 470 CC-view and 484 MLO-view borders into 2-10 clusters. The mean
      coefficients of the borders within a given cluster defined the "filter" shape,
      and the individual borders were translated and rotated to best match that filter
      shape. The average rms differences between the individual borders and the
      "filter" were computed as were the standard deviations of those differences. The
      optimally shifted and rotated borders were refit with the above polynomial
      equations, and plotted for visual evaluation of clustering success. Both
      polynomial fits were adequate with rms errors of about 2 mm for the 2-coefficient
      equation, and about 1 mm for the 3-coefficient equation. Although the fits to the
      original borders were superior for the 3-coefficient equation, the matches to the
      "filter" borders determined by clustering were not significantly improved. A
      variety of modified clustering methods were developed and utilized, but none
      produced major improvements in clustering. Results indicate that 3 or 4 filter
      shapes may be adequate for each mammographic projection (CC- and MLO-view). To
      account for the wide variations in exposures observed at the peripheral regions
      of breasts classified to be of a particular shape, it may be necessary to employ
      different filters for thin, medium and thick breasts. Even with this added
      requirement, it should be possible to use a small number of filters as desired.

PMID- 9650185
TI  - Optimally weighted wavelet transform based on supervised training for detection
      of microcalcifications in digital mammograms.
AB  - We are developing a computer-aided diagnosis (CAD) scheme for detection of
      clustered microcalcifications in digital mammograms. The use of an empirically
      chosen wavelet and scale combination for detection of microcalcifications as an
      initial step of the CAD scheme has been reported by us previously. In this study,
      we developed a technique for optimizing the weights at individual scales in the
      wavelet transform to improve the performance of our CAD scheme based on the
      supervised learning method. In the learning process, an error function was
      formulated to represent the difference between a desired output and the
      reconstructed image obtained from weighted wavelet coefficients for a given
      mammogram. The error function was then minimized by modifying the weights for
      wavelet coefficients by means of a conjugate gradient algorithm. The Least
      Asymmetric Daubechies' wavelets were optimized with 297 regions of interest
      (ROIs) as a training set by a jackknife method. The performance of the optimally
      weighted wavelets was evaluated by means of receiver-operating characteristic
      (ROC) analysis by use of the above set of ROIs. The analysis yielded an average
      area under the ROC curve of 0.92, which outperforms the difference-image
      technique used in our existing CAD scheme, as well as the partial reconstruction
      method used in our previous study.

PMID- 9650186
TI  - Computer-aided diagnosis: automatic detection of malignant masses in digitized
      mammograms.
AB  - A computerized method to automatically detect malignant masses on digital
      mammograms based on bilateral subtraction to identify asymmetries between left
      and right breast images was developed. After the digitization, in order to align
      left and right mammograms the breast border and nipple were automatically
      detected. Images were corrected to avoid differences in brightness due to the
      recording procedure. Left and right mammograms were subtracted and a threshold
      was applied to obtain a binary image with the information of suspicious areas.
      The suspicious regions or asymmetries were delimited by a region growing
      algorithm. Size and eccentricity tests were used to eliminate false-positive
      responses and texture features were extracted from suspicious regions to reject
      normal tissue regions. The scheme, tested in 70 pairs of digital mammograms,
      achieved a true-positive rate of 71% with an average number of 0.67 false
      positives per image. Computerized detection was evaluated by using free-response
      operating characteristic analysis (FROC). An area under the AFROC (A1) of 0.667
      was obtained. Our results show that the scheme may be helpful to the radiologists
      by serving as a second reader in mammographic screening. The low number of false
      positives indicates that our scheme would not confuse the radiologist by
      suggesting normal regions as suspicious.

PMID- 9650187
TI  - Evaluation of imaging geometries calculated from biplane images.
AB  - A technique is developed that will calculate accurate and reliable imaging
      geometries and three-dimensional (3D) positions from biplane images of a
      calibration phantom. The calculated data provided by our technique will
      facilitate accurate 3D analysis in various clinical applications. Biplane images
      of a Lucite cube containing lead beads 1 mm in diameter were acquired. After
      identifying corresponding beads in both images and calculating their image
      positions, the 3D positions of the beads relative to each focal spot were
      determined. From these data, the transformation relating the 3D configurations
      were calculated to give the imaging geometry relating the biplane views. The 3D
      positions of objects were determined from the biplane images along with the
      corresponding imaging geometries. In addition, methods are developed to evaluate
      the quality of the calculated results on a case-by-case basis in the clinical
      setting. Methods are presented for evaluating the reproducibility of the
      calculated geometries and 3D positions, the accuracy of calculated object sizes,
      and the effects of errors due to time jitter, variation in user-indication,
      centering, and distortions on the calculated geometries and 3D reconstructions.
      The precision of the translation vectors and rotation matrices of the calculated
      geometries were within 1% and 1 degree, respectively, in phantom studies, with
      estimated accuracies of approximately 0.5% and 0.4 degree, respectively, in
      simulation studies. The precisions of the absolute 3D positions and orientations
      of the calculated 3D reconstructions were approximately 2 mm and 0.5 degree,
      respectively, in phantom studies, with estimated accuracies of approximately 1.5
      mm and 0.4 degree, respectively, in simulation studies. This technique will
      provide accurate and precise imaging geometries as well as 3D positions from
      biplane images, thereby facilitating 3D analysis in various clinical
      applications. We believe that the study presented here is unique in that it
      represents the first steps toward understanding and evaluating the reliability of
      these 3D calculations in the clinical situation.

PMID- 9650188
TI  - Identification of lung regions in chest radiographs using Markov random field
      modeling.
AB  - The authors present an algorithm utilizing Markov random field modeling for
      identifying lung regions in a digitized chest radiograph (DCR). Let x represent
      the classifications of each pixel in a DCR as either lung or nonlung. We model x
      as a realization of a spatially varying Markov random field. This model is
      developed utilizing spatial and textural information extracted from samples of
      lung and nonlung region-types in a training set of DCRs. With this model, the
      technique of Iterated Conditional Modes is used to determine the optimal
      classification of each pixel in a DCR. The algorithm's ability to identify lung
      regions is evaluated on a testing set of DCRs. The algorithm performs well
      yielding a sensitivity of 90.7% +/- 4.4%, a specificity of 97.2% +/- 2.0%, and an
      accuracy of 94.8% +/- 1.6%. In an attempt to gain insight into the meaning and
      level of the algorithm's performance numbers, the results are compared to those
      of some easily implemented classification algorithms.

PMID- 9650189
TI  - A comprehensive physical image quality evaluation of a selenium based digital x
      ray imaging system for thorax radiography.
AB  - A selenium based digital x-ray system dedicated to chest radiography has been
      installed by the UK Department of Health's Medical Devices Agency at Leeds
      General Infirmary, UK, to undergo a comprehensive evaluation, including the
      physical image quality. The underlying characteristics which define the overall
      image quality of a system are the following: sensitometric response, modulation
      transfer function, and noise power spectrum. These have been measured objectively
      on preprocessed digital data acquired under relevant radiographic conditions. The
      image data is further processed prior to hard copy display. The displayed image
      quality may only be measured subjectively; threshold contrast detail
      detectability is such a measure which can be related to the objective measures of
      image quality. The objective imaging characteristics suggest that Thoravision has
      a significant advantage over conventional radiography imaging systems. However,
      subjective measures have demonstrated that the image processing can have a
      significant effect on the perceived image quality. Thoravision has the potential
      to deliver a significantly improved image quality to clinicians with no increase
      in radiation exposure to the patient, or image quality may be maintained with a
      reduction in radiation exposure. Digital image processing is central to the
      efficiency with which it achieves this.

PMID- 9650190
TI  - Automated segmentation of anatomic regions in chest radiographs using an adaptive
      sized hybrid neural network.
AB  - The purposes of this research are to investigate the effectiveness of our novel
      image features for segmentation of anatomic regions such as the lungs and the
      mediastinum in chest radiographs and to develop an automatic computerized method
      for image processing. A total of 85 screening chest radiographs from Johns
      Hopkins University Hospital were digitized to 2 K by 2.5 K pixels with 12 bit
      gray scale. To reduce the amount of information, the images were smoothed and
      subsampled to 256 by 310 pixels with 8 bit. The determination approach consists
      of classifying each pixel into two anatomic classes (lung and others) on the
      basis of several image features: (1) relative pixel address (Rx, Ry) based on
      lung edges extracted through image processing using profile, (2) density
      normalized from lungs and mediastinum density, and (3) histogram equalized
      entropy. The combinations of image features were evaluated using an adaptive
      sized hybrid neural network consisting of an input, a hidden, and an output
      layer. Fourteen images were used for the training of the neural network and the
      remaining 71 images for testing. Using four features of relative address (Rx,
      Ry), normalized density, and histogram equalized entropy, the neural networks
      classified lungs at 92% accuracy against test images following the same rules as
      for the training images.

PMID- 9650191
TI  - A semianalytic model to investigate the potential applications of x-ray scatter
      imaging.
AB  - Although x-ray scatter is generally regarded as a nuisance that reduces
      radiographic contrast (C) and the signal-to-noise ratio (SNR) in conventional
      images, many technologies have been devised to extract useful information from
      the scattered x rays. A systematic approach, however, for analyzing the potential
      applications of x-ray scatter imaging has been lacking. Therefore, we have
      formulated a simple but useful semianalytic model to investigate C and SNR in
      scatter images. Our model considers the imaging of a target object against a
      background material of the same dimensions when both are situated within a water
      phantom. We have selected biological materials (liver, fat, bone, muscle, blood,
      and brain matter) for which intermolecular form factors for coherent scattering
      were available. Analytic relationships between C and SNR were derived, and
      evaluated numerically as the target object thickness (0.01-40 mm) and photon
      energy (10-200 keV) were systematically varied. The fundamental limits of scatter
      imaging were assessed via calculations that assumed that all first-order scatter
      exiting the phantom, over 4 pi steradians, formed the signal. Calculations for a
      restricted detector solid angle were then performed. For the task of imaging
      white brain matter versus blood in a 15 cm thick water phantom, the maximum SNR,
      over all energies, for images based on the detection of all forward scatter
      within the angular range 2 degrees-12 degrees is greater than that of primary
      images for target object thicknesses < or = 23 mm. Use of the backscattered x
      rays within the range 158 degrees-178 degrees to image objects 3 cm below the
      surface of a 25 cm thick water phantom allows the liver to be distinguished from
      fat with a SNR superior to that of primary imaging when the objects are < or = 22
      mm thick. Our analysis confirms the usefulness of scattered x rays, and provides
      simple methods for determining the regimes of medical interest in which x-ray
      scatter imaging could outperform conventional imaging.

PMID- 9650192
TI  - The effect on dose to computed tomography phantoms of varying the theoretical x
      ray spectrum: a comparison of four diagnostic x-ray spectrum calculating codes.
AB  - Theoretical x-ray spectra calculated by four different codes for the same tube
      parameters are compared by calculating and measuring doses to computed tomography
      (CT) body and head phantoms. The effect on the 120 kV spectrum, and hence on the
      calculated dose, of varying the anode angle, tube voltage, and total filtration
      of the x-ray tube is investigated. Codes used were those of Nowotny and Hofer
      (XCOMP), Boone, Iles, and Tucker et al. The code based on the work of Tucker et
      al. produced calculated doses noticeably lower than the other codes and compared
      best to the measured value. The variation in calculated dose between the Tucker
      code and the others is of the same order as the variation introduced by
      uncertainties in total filtration of about 20%, in peak tube voltage of +/- 4 kV,
      and in change of anode angle from 7 degrees to 13 degrees.

PMID- 9650193
TI  - Panoramic radiology quality assessment.
AB  - A procedure is proposed for performing noninvasive x-ray quality assessment tests
      on panoramic radiology equipment. A simple cardboard tube jig eliminates relative
      motion between the measurement system and the narrow, collimated x-ray beam.
      Accurate measurements of beam HVL, x-ray exposure coefficient of variation and mA
      linearity may be obtained. Use of the tube jig permits easy and routine
      monitoring of these important x-ray parameters as well as consistency checks of
      tube output. Film/screen contact also should be routinely checked in the clinic.

PMID- 9650194
TI  - Exposure and dose in panoramic radiology.
AB  - Panoramic radiology entrance skin exposure (ESE) was measured for a Siemens
      Orthopantomograph 10 E using a thimble chamber and TLDs. Thimble chamber
      measurements are shown to be inaccurate for the moving, narrow beam panoramic
      scan geometry due to partial volume and partial charged-particle equilibrium
      effects. For 75 KVp, 8 mA panoramic scans the TLD measured beam central ray ESE
      on the scan central plane (patient midsagittal plane) was an approximately
      constant 20 mR for the first 7.5 cm from the entrance slit. A theoretical model
      of central plane ESE for a fixed rotation center agrees very well with the TLD
      measurements and is consistent with all of the known ESE (and dose) properties
      near rotation centers. Head phantom skin dose measurements demonstrate the
      dependence of skin dose on exact equipment mode of use and patient anatomy.
      Central plane, beam central ray ESE is judged to be a convenient, universal
      measure of panoramic radiology radiation output.

PMID- 9650195
TI  - Specific absorption rate ratio patterns of cylindrical ultrasound transducers for
      breast tumors.
AB  - The purpose of this paper is to examine the optimal driving frequency and to
      configure the ultrasound energy deposition schema for a various size and location
      of breast tissues when a portion or the entire cylindrical ultrasound transducer
      is employed for breast hyperthermia treatments. This work employs a computer
      simulation program based on an ideal ultrasound power deposition from a
      cylindrical transducer. The ultrasound power within the breast is assumed to be
      exponentially attenuated according to the penetration depth of the ultrasound
      beam and a uniform absorption for the entire breast is also assumed. The
      distribution of the specific absorption rate (SAR) ratio is employed to determine
      the heating pattern of a set of given parameters. The control parameters
      considered are the ultrasound frequency in the breast tissue, the active portion
      of cylindrical transducer, and the shifting distance between the central axes of
      the breast and the transducer. The effect of the breast size on the SAR ratio is
      also considered. Simulation results demonstrate that the breast size, the
      ultrasound frequency in breast tissue, the shifting distance, and the active
      portion of the cylindrical transducer are the potential parameters for
      influencing the distribution of the SAR ratio. High frequencies should be used
      for the superficial heating treatments and the active portion of the transducer
      can be changed to obtain a region with an appropriate SAR ratio to cover the
      treatment region. Low frequencies are used for deep heating treatments and the
      region of the high SAR ratio can be moved by shifting the transducer and its
      pattern is varied with the transducer's active portion. The distribution of the
      SAR ratio indicates the domain of treatable tumor size and tumor depth for a
      given set of parameters (driving frequency, shifting distance and active portion
      of the transducer, as well as breast diameter). Findings of this study can be
      used to know whether or not the tumor is treatable as well as to select the
      optimal driving frequency and the appropriate active portion of the cylindrical
      transducer for a treatment, and hopefully to design an appropriate cylindrical
      ultrasound heating system for breast tumors.

PMID- 9650196
TI  - Measurement of small inter-scan fluctuations in voxel dimensions in magnetic
      resonance images using registration.
AB  - We present a method to estimate fluctuations in voxel dimensions in MR images. In
      the proposed method images of a standard test object are acquired serially and
      registered to an initial dataset. We present the results of experiments where
      changes in voxel dimensions between 0.1% and 2% were prescribed and measured with
      an accuracy of 0.02%. The method can be integrated as part of a standard MRI
      Quality Assurance program and may also be useful to correct for inter-scan
      variability introduced by fluctuations in gradient performance.

PMID- 9650197
TI  - Estimating RBEs at clinical doses from microdosimetric spectra.

PMID- 9650198
TI  - [Analysis of telomeric length in epithelial carcinoma of the ovary].
AB  - BACKGROUND: As a consequence of the high cell division rate, telomeric repeat
      reduction in human tumor cells, giving rise to genetic instability, has recently
      been described. The aim of this study was to analyze by Southern blot telomeric
      length alterations in a retrospective group of patients with ovarian epithelial
      carcinoma. PATIENTS AND METHODS: Tumor and corresponding normal DNA were isolated
      from paraffin-embedded tissue of 16 patients with ovarian epithelial carcinoma.
      Telomeric Restriction Fragments (TRF) were studied by Southern blot and
      densitometric analysis. RESULTS: No telomere alterations were detected in 37.5%
      of patients (6/16). Of the remaining ten, 5 were found to have telomere reduction
      and five telomere elongation. No significant correlation was found between
      clinicopathological variables, response to chemotherapy, survival rate or time to
      progression, and telomere length alterations. CONCLUSIONS: In ovarian epithelial
      carcinoma telomere elongation may be a marker of the presence of immortal cells
      within the tumor, but telomere or the absence of telomeric alterations do not
      rule out the presence of these cells. Although TRF analysis can be performed in
      paraffin-embedded tissues, it is not the best indicator of telomerase activity
      and thus of tumor aggressiveness in early stages of this carcinoma.

PMID- 9650199
TI  - [Factors associated with an atherogenic lipid profile in premenopausal women
      without clinical cardiovascular disease].
AB  - BACKGROUND: To investigate different factors associated to a non desirable lipid
      profile in premenopausal women without cardiovascular disease. To determine the
      independent factors of lipid profile as a whole of the sample, for planning
      preventive studies. PATIENTS AND METHODS: We study (March 1994 to June 1996)
      premenopausal women with alcohol consumption less than 14 g/day and normal serum
      level of glucose. Group I: women with a non desirable lipid profile (total
      cholesterol [TCH, mg/dl]/high density lipoprotein cholesterol [HDL-C, mg/dl] > or
      = 5). Group II: with a desirable lipid profile (TCH/HDL-C < 5). The following
      factors were analyzed: age, body mass index (BMI), waist/hip ratio (W/H),
      systolic blood pressure (SBP, mmHg), fasting plasma insulin (fpI, microU/ml),
      cigarette smoke (CS) and presence of parents with history of non insulin
      dependent diabetes mellitus (NIDDM) or hypertension. STATISTICAL METHODS: Mann
      Whitney and Student statistics. Contingency-table analysis (chi 2 statistic).
      Pearson correlation and multiple linear regression. RESULTS: We analyzed 126
      women (age = 30 +/- 8.2; 95% CI, 29-32; TCH = 197 +/- 36; 95% CI, 190-203 mg/dl),
      with 20 women (group I) and 106 (group II). Women from group I had higher values
      of W/H (0.83 +/- 0.04 vs 0.78 +/- 0.06; p < 0.001), BMI (29.9 +/- 9 vs 24.6 +/-
      4.9; p < 0.03), fpI (12.9 +/- 10.4 vs 7.8 +/- 3.5; p < 0.05), SBP (125.9 vs 117;
      p < 0.02), as well as higher percentage of smokers (75 vs 40%; p < 0.01) and
      parents with NIDDM (60 vs 26%; p < 0.01) or hypertension (60 vs 49%; NS). No
      differences of age were detected (32 +/- 7.3 vs 30 +/- 8.3; NS). BMI (0.32; p <
      0.01), W/H (0.50; p < 0.01), SBP (0.27; p < 0.01) and fpI (0.33; p < 0.01) were
      positively correlated with TCH/HDL-C ratio (n = 126). In multiple regression
      analysis (n = 126), W/H (regression coefficient = 6.1; 95% CI, 3.1-9.1), fpI
      (regression coefficient = 0.045; 95% CI, 0.018-0.072) and CS (regression
      coefficient = 0.5; 95% CI, 0.336-0.667) were the only independent predictors (p <
      0.01) of the TCH/HDL-C ratio, controlling a 46% of the variance (R2 = 0.46).
      CONCLUSIONS: Our data indicates that central obesity, hyperinsulinemia and
      cigarette smoke are independently associated to a high risk cardiovascular lipid
      profile in premenopausal women without cardiovascular disease. This study
      suggests the importance of these factors in the management of early lipid control
      in these women.

PMID- 9650200
TI  - [Gallium-67 (Ga-67) scintigraphy in tuberculosis and Mycobacterium avium-M.
      intracellulare infections in patients with HIV infections].
AB  - BACKGROUND: Diagnosis of mycobacterioses in HIV infected patients is sometimes
      difficult because of atypical findings. The aim of this study was to assess the
      utility of gallium scintigraphy in diagnosis of AIDS related mycobacterioses in
      patients with fever of unknown origin. PATIENTS AND METHODS: We retrospectively
      reviewed the scans of 220 HIV(+) patients with fever (176 males [80%] and 44
      females) who were evaluated with conventional diagnostic procedures at least of a
      week before. RESULTS: Gallium scintigraphy was positive in 114 patients (51%) and
      negative in 106 (49%). Mycobacteria were isolated in 83 patients (38%), 75 of
      these patients (90%) had a positive scintigraphy (sensitivity 90%; specificity
      71%). Positive predictive value was 66% and negative predictive value was 92%.
      Mycobacterium avium-M. intracellulare (MAI) and M. tuberculosis were diagnosed in
      22 (29%) and 53 (71%) HIV(+) patients, respectively. Seventy one (94%) of 75
      patients with mycobacterioses had gallium uptake in at least two localizations.
      CONCLUSIONS: 67Ga scintigraphy is very useful in HIV(+) patients with fever of
      unknown origin. A negative gallium scintigraphy makes unlikely the diagnosis of
      mycobacterioses.

PMID- 9650201
TI  - [Treatment of lymphoma in the aged].

PMID- 9650202
TI  - [The European Union begins its road to orphan drugs].

PMID- 9650203
TI  - [Smoking and school children: context, opinions and behavior].
AB  - BACKGROUND: This paper studies smoking epidemiology in school-age students.
      MATERIAL AND METHODS: A cross-sectional survey of 8th grade students (13-14 years
      old) in the schools of Barcelona (Catalonia, Spain) in 1987, 1992 and 1994.
      RESULTS: The perception of smoking in the students environment has decreased. The
      proportion of regular smokers decreases, from 12.6% in 1987 to 9.5% in 1994 (p <
      0.05) (an annual decrease of 3.5%) although the proportion who experiment with
      tobacco remains table. CONCLUSIONS: There is a decrease in the prevalence of
      regular smoking in the school-age population (13-14 years-old) in Barcelona
      (Spain).

PMID- 9650204
TI  - [Quality of life of patients with bone marrow transplant].

PMID- 9650205
TI  - [Pathogenic mechanisms in systemic vasculitis. New concepts].

PMID- 9650206
TI  - [Polyglobulia in the Canadas del Teide? Preliminary results of a prospective
      study].

PMID- 9650207
TI  - [Disseminated Mycobacterium kansasii infection with skin involvement in a patient
      with acquired immunodeficiency syndrome].

PMID- 9650208
TI  - [Impact of consensus for control of cholesterolemia in Spain].

PMID- 9650209
TI  - [Advice of the general practitioner and healthy life styles: is there an
      alternative to passivity caused by technical and ethical difficulties?].

PMID- 9650210
TI  - [Ambulatory versus stationary radiotherapy].

PMID- 9650211
TI  - [Comparison of 51Cr-EDTA with 99m-Tc-DTPA slope clearance for estimation of
      glomerular filtration rate using the one compartment model].
AB  - AIM: Of this study is to determine the relationship between 51Cr-EDTA and 99mTc
      DTPA slope clearance applying the "one-compartment model". METHODS: The "one
      compartment model" was chosen to calculate and to compare the glomerular
      filtration rates of 25 patients with normal and pathological creatinin values
      after injection of 51Cr-EDTA and 99mTc-DTPA simultaneously. RESULTS: The two
      clearance values correlated well (r = 0.996), and the 99mTc-DTPA clearance was
      systematically higher (28%). The 99mTc-DTPA was calculated and compared after
      taking three plasma samples. Taking two samples, only minor differences were seen
      and the correlation was high (r = 0.992). CONCLUSION: The results of this study
      encouraged us to adopt the use of 99mTc-DTPA instead of 51Cr-EDTA in determining
      the glomerular filtration applying the "one-compartment model" in slope with two
      plasma samples.

PMID- 9650212
TI  - [Clinical relevance of I-123/I-131-MIBG scintigraphy in intestinal carcinoid
      tumors].
AB  - AIM: Of this retrospective study was to determine the value of MIBG-scintigraphy
      in patients with intestinal carcinoids dependent on histological, clinical, and
      biochemical parameters. METHODS: In 15 patients uptake in carcinoid tumors and
      metastasis was correlated with location of the primary tumor, intra- and
      extrahepatic tumor masses, histology, immunhistochemistry, neuroendocrinological
      markers, and clinical symptoms. RESULTS: High uptake was to be seen almost only
      in tumor masses of primary tumors located in the terminal ileum. There also was a
      positive correlation with clinical symptoms for carcinoids and urinary 5-HIAA
      level. No correlation between MIBG uptake and tumor masses, histology, and most
      of the immunhistochemical and neuroendocrinological markers could be found.
      CONCLUSION: There is a limited indication for MIBG-scintigraphy in follow up of
      intestinal carcinoids. In patient with proven uptake MIBG scintigraphy is
      suitable for long-term follow up and therapy monitoring.

PMID- 9650213
TI  - [Kinetics of receptor-mediated radiotoxicity of 16alpha-[125I]-iodostradiol
      3,17beta].
AB  - AIM: The radiocytotoxic effects in estrogen receptor (ER) containing MCF-7 cells
      of a mamma carcinoma were investigated following incubation with [125I]E ranging
      from 1 h to 24 h. METHODS: The receptor status of the cells was confirmed by
      immunohistochemical staining. The accumulation of [125I]E in MCF-7 cells was
      tested in the presence and absence of radioinert E and [127I]E and in ER-negative
      cells in comparison to ER-positive cells. The subcellular distribution was
      investigated in 0.25 M Saccharose by ultra centrifugation. The radiocytotoxicity
      was assessed in ER-positive and negative cells by a standard colony forming assay
      after incubating with [125I]E (1.85 kBq/ml-55.5 kBq/ml) for 1, 2, 4, 8, 12, and
      24 h. RESULTS: A significant cytotoxicity was observed only when ER-rich MCF-7
      cells were incubated with [125I]E alone. The maximal cytotoxic effect was a
      reduction of survival fraction to 20-25%. This was achieved at radioactivity
      concentrations > 37 kBq/ml. Maximal effect was seen after 8 h incubation,
      extension of incubation time did not further increase toxicity. CONCLUSION: The
      results suggest that the radioactivity was bound to ER. Through their nuclear
      localization radioestrogens tagged with radionuclides emitting very low energy
      electrons (Auger electrons) bear potential for therapy by ER-mediated deposition
      of lethal doses of ionizing radiation to single cells without affecting
      neighbouring cells. But, instead of 125I the shorter-living 123I shall be used
      for labelling because the deciding radiation effectes occur within the first 8 h.

PMID- 9650214
TI  - Adrenocortical scintigraphy with 131I-6-beta-iodomethyl-norcholesterol (NP 59) in
      bilateral adrenocortical carcinoma.
AB  - A case of a 49-year-old man suffering from bilateral adrenocortical carcinoma
      with local and secondary rapid progression is reported. The results of
      adrenocortical scintigraphy (NP 59) and histological findings allowed the
      diagnosis. This case report and a literature review showed the importance of
      using adrenocortical scintigraphy as a complementary imaging procedure of CT or
      MR images.

PMID- 9650215
TI  - [Septal myocardial perfusion in complete left bundle branch block: case report
      and review of the literature].
AB  - Myocardial scintigraphy was performed three times in a 55-year-old woman with
      left bundle branch block (LBBB). A significant LAD stenosis had been excluded by
      coronary angiography. The first scintigraphy was performed with Tc-99m sestamibi
      after submaximal bicycle exercise and revealed a septal perfusion deficit. This
      deficit could not be reproduced in the following examinations after
      pharmacological stress testing with dipyridamole using both Tl-201 and Tc-99m
      sestamibi. Perfusion at rest assessed with Tl-201 was normal in all studies. It
      is concluded that pharmacological stress testing with dipyridamole is to be
      preferred in patients with LBBB. With respect to the accuracy of myocardial
      perfusion imaging the choice of the radiopharmaceutical plays a less important
      role.

PMID- 9650216
TI  - [Scintigraphic assessment of function in renal dystopia].
AB  - In patients with renal dystopia radionuclide urography in commonly used technique
      may yield inaccurate results concerning split renal function. In a case of
      unilateral pelvic kidney a simple strategy to avoid this methodical error is
      demonstrated.

PMID- 9650218
TI  - [Pathogenetic differentiation of the bone superscan using bone marrow
      scintigraphy].
AB  - The case of a 54 year old patient suffering from a prostatic carcinoma is
      presented. At the time of diagnosis multiple bone metastases were detected by
      bone scintigraphy. An initial improvement was observed following antiandrogenic
      therapy. After three years the patient presented with increasing bone pain, which
      was most prominent in the knee joints. A "superscan" was found in bone
      scintigraphy with an unusually high uptake in the peripheral skeleton. Bone
      marrow scinitgraphy showed a nearly complete metastatic displacement of central
      bone marrow and a peripheral marrow extension as explanation for the bone scan
      findings.

PMID- 9650217
TI  - Pulmonary tumor microembolism.
AB  - Pulmonary tumor embolism is an often missed antemortem diagnosis in patients with
      cancer and respiratory failure. Although rare, this complication is an important
      cause of additional morbidity. Referred for radionuclide pulmonary perfusion and
      ventilation scintigraphy, a typical pattern of multiple subsegmental peripheral
      defects on perfusion lung scanning without matching ventilation defects,
      suggesting a high probability of pulmonary thromboembolism, often leads to false
      conclusions. We present a case of bilateral multiple subsegmental mismatched
      defects in lung ventilation perfusion scintigraphy, where autopsy confirmed the
      diagnosis of pulmonary tumor embolism, secondary to an undifferentiated ductal
      type adenocarcinoma of the pancreas. Pulmonary tumor embolism is an entity to
      keep in mind in patients treated for carcinoma presenting with (sub) acute
      dyspnea.

PMID- 9650219
TI  - Remodelling: historical perspectives and definition of terms.
AB  - The changes that occur in both the structure and geometry of blood vessels in
      pathological conditions has been termed remodelling. The importance of the
      changes in geometry have only been recently widely appreciated, although
      geometric remodelling has been recognized for more than 30 years. Geometric
      remodelling can be favourable, as occurs with compensatory enlargement, or
      unfavourable, as with constriction. Vascular remodelling is recognized to occur
      in a variety of pathological conditions, including atherosclerosis, hypertension,
      arterio-venous grafts, and following restenosis. A better understanding of the
      pathophysiology should permit development of new therapeutic strategies to treat
      these conditions.

PMID- 9650220
TI  - Arterial remodelling by atherosclerosis.
AB  - Until recently, plaque formation was considered to be the only determinant of
      atherosclerotic luminal narrowing. Recent post-mortem and intravascular
      ultrasound studies, however, revealed that arterial remodelling is another
      important determinant of luminal narrowing in de novo atherosclerosis. The change
      in total arterial circumference relative to a reference cross-section ranges from
      excessive enlargement with an actual increase in lumen to arterial shrinkage
      contributing to lumen narrowing. The mechanisms responsible for this spectrum of
      remodelling are unknown, but their identification will be important for the
      potential development of therapeutic strategies to promote favourable
      remodelling.

PMID- 9650221
TI  - Remodelling and restenosis: insights from animal studies.
AB  - Animal studies have been instrumental in elucidating the process of remodelling
      and its contribution to restenosis relative to neointimal formation following
      angioplasty. The majority of studies have utilized rabbit, porcine and nonhuman
      primate models of vascular injury. Despite the use of different experimental
      models, different forms of vascular injury, different methods of analysis and
      different definitions of arterial remodelling, all animal studies, with rare
      exceptions, have demonstrated the importance of remodelling in the maintenance of
      vascular patency in both atherogenesis and in restenosis following angioplasty.
      The finding that remodelling in the non-human primate is most comparable to that
      that occurs in man suggests that there may be a genetic predisposition to the
      balance of neointimal formation and arterial remodelling following vascular
      injury.

PMID- 9650222
TI  - Remodelling and restenosis: intravascular ultrasound studies.
AB  - Remodelling, defined as a change in total vessel area, was demonstrated to be
      another important mechanism of restenosis after coronary angioplasty in a study
      utilizing intravascular ultrasound. In this study, remodelling was also
      demonstrated to be bidirectional (constrictive modelling and adaptive
      remodelling). A recent serial intravascular ultrasound study revealed that time
      course of remodelling after coronary angioplasty was typically biphasic; early
      (post-procedure-1 month) adaptive remodelling and late (1 month-6 months)
      constrictive remodelling. Remodelling after coronary angioplasty should be
      regarded not only as a cause of restenosis but also as a mechanism maintaining
      patency.

PMID- 9650223
TI  - The role of the extracellular matrix in arterial remodelling.
AB  - The extracellular matrix is now recognized as a biologically active and dynamic
      composition of structural, adhesive, and counteradhesive fibrous proteins
      embedded in a hydrated ground substance of glycosaminoglycans and proteoglycans.
      The ability of resident cells to detect small differences in the specific
      combination, concentration and distribution of matrix components suggests that
      perturbation of the homeostatic matrix can lead to remodelling following
      angioplasty. Recent studies reviewed herein have focused on how alterations of
      the relative composition of matrix components ultimately leads to changes in cell
      growth, behaviour and differentiation, all of which can significantly contribute
      to remodelling of the vascular wall following injury. These cell-matrix
      interactions may provide novel therapeutic targets in the prevention of
      unfavourable remodelling that leads to restenosis.

PMID- 9650224
TI  - Remodelling: therapeutic opportunities.
AB  - Restenosis after angioplasty has been recently attributed to a lack of
      compensatory enlargement and/or chronic constrictive remodelling, rather than
      neointimal growth. Also, restenosis occurring after stent has been clearly
      related to neointimal growth. This clarification has dramatically helped in
      designing strategies targeted against the appropriate mechanisms. The mechanism
      of stent-related restenosis has been the most studied and several
      antiproliferative agents including gene therapy and radioactive stents have been
      successfully tested. Constrictive remodelling has been identified more recently
      and its pathophysiological mechanism remains poorly understood. Control of
      extracellular matrix metabolism might be an important pathway. Moreover,
      detection of the arteries that will 'enlarge' should avoid any preventive
      strategy including systematic stenting.

PMID- 9650225
TI  - The physician's moral obligations to the pregnant woman, the fetus, and the
      child.
AB  - The moral obligations and ethical duties of health care professionals responsible
      for the care of a pregnant woman, a fetus, and a child are complex and evolve
      with gestation and birth. Well-intentioned physicians and others concerned with
      the interests of pregnant women and their fetuses may disagree about the moral
      status of the fetus and ethical duties owed to both the woman and fetus. This
      article lays out a framework for thinking about these issues from several
      perspectives.

PMID- 9650226
TI  - Ethical issues in reproductive genetics.
AB  - Because of technological developments in reproductive genetics, couples now have
      many options not available a decade ago. Some developments are controversial and
      deeply divide our society. This article examines some of these issues and
      establishes guidelines of approach.

PMID- 9650227
TI  - Ethical dilemmas in the delivery room.
AB  - The decision to withhold or withdraw life support in the neonatal intensive care
      unit (NICU) is common but is never routine. Often, moral demands make such
      decisions difficult and emotionally exhausting. But, what is perhaps more
      challenging from the moral point of view is the transition from the delivery room
      to the NICU. A satisfactory analysis of the moral issues of delivery room
      practices must include a discussion of quality of life, the best interest of the
      infant, the best interests of the family members, and futile treatment. Although
      these topics are relevant in any discussion of the moral justification of the
      omission, withdrawal, or use of treatment for patients, they are especially
      telling when entertained in the context of the transition of the fetus to a
      newborn. This article uses these four topics as a moral compass for certain
      decisions made in the delivery room.

PMID- 9650228
TI  - Ethical issues in the care of extremely low birth weight infants.
AB  - This article examines the difficulties in making decisions about the medical
      treatment of infants who have uncertain viability because of extremely low birth
      weight. The advantages and disadvantages of three systematic approaches are
      reviewed. An approach called "provisional intensive care for all" may offer the
      most benefit and cause the least harm. With this approach, all liveborn infants
      would be presumed viable and would receive intensive care, at least initially.
      After further assessment of the infant, the parents would be informed as fully as
      possible about the possible outcome of continuing intensive care. The treating
      physicians would offer the parents the options of continuing intensive care or
      withdrawing it and providing basic care. Although the physicians would provide
      recommendations based on their best medical judgment, they would be prepared to
      support and carry out the parents' decision.

PMID- 9650229
TI  - Futility considerations in the neonatal intensive care unit.
AB  - The purpose of this article is to summarize and comment on the history of medical
      decision making in the neonatal intensive care nursery, emphasizing
      considerations of futility. Several epochs will be described, with shifting roles
      of health care providers, the infant's family, and proxies for society at large.
      Futility has been an issue in the intensive care of newborn infants throughout
      the last 35 years. Long before the Baby Doe regulations and the formation of
      ethics committees, neonatologists tried to determine which care measures were
      indicated. Given the frequency of severe malformations, birth asphyxia, and
      extreme prematurity, it has been a common event for the responsible physician to
      ask himself: will this treatment be beneficial or merely futile? As the
      therapeutic armamentarium became more powerful and complex, the choices from
      among a possible array of interventions became increasingly difficult. The
      autonomy of parents as decision makers was increasingly affirmed. In the 1980s,
      the federal government, the courts, and frequent malpractice suits set boundaries
      on medical decision making. In the 1990s, third party payors became increasingly
      assertive in limiting resource expenditure. These legal and societal mandates are
      frequently at variance with one another. Thus the issue of medical futility, as
      it applies to neonates in the United States, must be considered unresolved.

PMID- 9650230
TI  - Ethical dilemmas in medical innovation and research: distinguishing
      experimentation from practice.
AB  - The words research and experimentation continue to have the power to evoke fear
      in potential subjects. But much of standard practice, particularly in critical
      care settings, involves interventions of unknown efficacy and safety. Innovation
      also abounds in practice settings, typically unchecked by prospective or
      retrospective review. Historical attention has focused on the conflict of
      interest of the physician/investigator, but contemporary safeguards have reduced
      the risks of research and increased the likelihood that the patient/subject will
      have the opportunity to make an informed choice. Innovation and untested
      interventions in practice, in contrast, are often unknown to the patient and lack
      institutional safeguards. Some common cliches that suggest that research is more
      to be feared than standard practice will be examined, leading to the following
      conclusions: defining an intervention as experimental may be less important in
      ethical terms than the quality of prospective and retrospective review and the
      standards for informed consent, and the concerns that led to regulation of
      research should now be directed toward unproven interventions and innovation in
      the practice setting.

PMID- 9650231
TI  - Reproductive health under managed care: expanding provider obligations.
AB  - The discussion of ethical issues in managed care can be focused on two general
      areas. The first of these is the impact of the shift toward managed care on the
      fiduciary relationship between health care professional and patient, including
      the issue of trust, the potential for conflict of interest, and the impact of
      cost-saving strategies on the clinician's ability to address a patient's health
      care needs. The second is the attention to justice that managed care demands.
      Health care professionals must take issues in both areas into account, attempting
      to balance obligations to individual patients with obligations to patients
      collectively. Strategies for doing so are discussed.

PMID- 9650232
TI  - Guidance on the use of PrP genotyping as an aid to the control of clinical
      scrapie. Scrapie Information Group.

PMID- 9650233
TI  - Cataracts in farmed Atlantic salmon (Salmo salar) in Ireland, Norway and Scotland
      from 1995 to 1997.
AB  - From 1995 to 1997 cataracts were observed in Atlantic salmon (Salmo salar) in
      Ireland, Norway and Scotland at around the time of smoltification (when
      freshwater fish become adapted to the hypertonic seawater) in both fresh- and
      seawater fish. Over 38,000 fish were screened for the presence of cataracts.
      Posterior cortical cataracts were the earliest and most consistent change,
      followed by perinuclear, equatorial and anterior cortical cataracts. On
      histological examination vacuolation of the lens fibres was consistently present
      in the posterior cortex. The pattern of the outbreak suggested that a nutritional
      factor was involved although the variable incidence and severity of the condition
      indicated that a number of modifying factors may have been involved in the
      expression of the condition.

PMID- 9650234
TI  - Clinical efficacy and safety of propofol or ketamine anaesthesia in dogs
      premedicated with medetomidine.
AB  - Combinations of medetomidine with either propofol or ketamine were compared for
      the sedation and induction of anaesthesia in dogs undergoing a variety of
      surgical (60 per cent) and non-surgical (40 per cent) procedures. Eighty-four
      dogs were used at four sites. Medetomidine was administered intramuscularly at a
      dose of 1000 micrograms/m2 body surface area 10 to 15 minutes before the
      induction of anaesthesia by the administration of propofol (n = 44) or ketamine
      (n = 40) dosed to effect. The dogs became sedated by medetomidine after a mean
      (sd) time of 6.7 (5.4) minutes, and their heart rates and respiration rates
      decreased. Sixteen of the dogs suffered an adverse effect, 13 of them vomited.
      Anaesthesia was induced by the intravenous administration of propofol (2.1 [0.7]
      mg/kg) or ketamine (3.7 [1.9] mg/kg), and further doses of the anaesthetic were
      given, depending on the length of the operation, once in 17 per cent, twice in 11
      per cent and three or more times in 24 per cent of the cases. The heart rate of
      the dogs anaesthetised with ketamine was significantly higher than that of the
      dogs anaesthetised with propofol, but there were no other significant
      physiological differences. There were 11 adverse side-effects in the ketamine
      group compared with five in the propofol group and they were generally more
      severe. The quality of the recovery from anaesthesia was considered to be smooth
      in 89 per cent of the propofol group but in only 63 per cent of the ketamine
      group.

PMID- 9650235
TI  - Use of metronidazole in equine acute idiopathic toxaemic colitis.
AB  - Sixteen cases of acute idiopathic toxaemic colitis developed in a veterinary
      hospital over a period of three years. Before the onset of colitis, 15 horses had
      received antibiotics, 11 had undergone general anaesthesia and various surgical
      procedures, and 10 had been treated with non-steroidal anti-inflammatory drugs.
      The horses had acute onset, profuse watery diarrhoea, profound depression, mild
      to moderate abdominal pain, reduced intestinal borborygmi, tachycardia,
      dehydration and endotoxic shock. Leucopenia, neutropenia and pyrexia were common
      early indicators of impending colitis. Metronidazole appeared to be an effective
      treatment; eight horses treated with metronidazole survived whereas five of seven
      horses that received other treatments, but no metronidazole, died or had to be
      euthanased. The aetiology of the colitis could not be determined, but the
      clinicopathological features resembled those of colitis attributed to an
      intestinal overgrowth of Clostridium perfringens type A. No Salmonella species
      were isolated from 52 samples of faeces, colonic contents and colonic mucosa
      which were collected from the horses antemortem and postmortem.

PMID- 9650236
TI  - Use of disease models in the development and evaluation of therapeutic agents.
AB  - A key part of the regulatory review of new therapeutic agents depends on a clear
      demonstration of their efficacy. There can be difficulties when the evaluations
      of efficacy depend only on in vitro studies, such as minimum inhibitory
      concentrations (MICs), and clinical field trials. The MIC data often correlate
      poorly with in vivo results, and field trials can suffer from the
      unpredictability of disease outbreaks and from differences in the severity of
      outbreaks at different sites. This paper discusses the use of experimentally
      induced diseases as a means of bridging the gap between the in vitro data and the
      results of field trials.

PMID- 9650237
TI  - Paralytic phycotoxins in monk seal mass mortality.

PMID- 9650238
TI  - Pancreatic necrosis in a llama.

PMID- 9650239
TI  - Detection of strangles carriers.

PMID- 9650240
TI  - Surgical treatment of oral stereotypies in horses.

PMID- 9650241
TI  - History of trauma and attempted suicide among women in a primary care setting.
AB  - The results of past research have demonstrated apparent links between suicidality
      and a history of sexual abuse or physical abuse. However, the relative predictive
      power of such abuse histories in explaining sucidality remains unknown, as does
      the potential relationship between sucidality and emotional abuse, physical
      neglect, and witnessing violence. In the current study, 151 women who presented
      for nonemergent medical care indicated whether they had experienced each of five
      types of abuse and whether they had ever attempted suicide. Similar to past
      research, increased rates of having attempted suicide were evident among women
      who had been sexually or physically abused. Rates of past suicide attempts were
      also higher among those who had experienced emotional abuse or had witnessed
      violence. However, many women indicated having experienced multiple forms of
      trauma. In a multivariate analysis, only sexual abuse and physical abuse were
      uniquely predictive of having attempted suicide. Results are discussed with
      regard to the potential importance of bodily intrusiveness during abuse as most
      predictive of subsequent suicidality.

PMID- 9650242
TI  - Correlates of sexual assault in Mexican American and white non-Hispanic
      adolescent males.
AB  - Psychosocial and emotional characteristics were assessed in a nonclinical sample
      of 1,385 adolescent Mexican American and White non-Hispanic males. Fifty-four
      males who reported being sexually assaulted one or more times were compared to
      1,331 males who reported no history of sexual assault. Sexually assaulted male
      victims were more emotionally distressed, socially isolated, deviant (e.g., lying
      & stealing), likely to affiliate with deviant peers, and to come from homes in
      which there was parental substance use, than males who did not report sexual
      assault. Significant differences were not found between Mexican American and
      White non-Hispanic assault victims. Implications of these findings are discussed.

PMID- 9650243
TI  - Immigrants and the criminal justice system: an exploratory study.
AB  - Experts have argued that there are significant barriers to recent immigrants' use
      of the criminal justice system. This exploratory study, using convenience
      samples, is among the first to look empirically at the experiences of recent
      immigrant victims with the criminal justice system in the United States. Contrary
      to expectations, we found that immigrants reported relatively few problems unique
      to foreign-born persons in dealing with the police and the courts, and that their
      satisfaction with the justice system was comparable to levels reported in studies
      of native-born victims. The results suggest that although recent immigrants'
      expectations of the criminal justice system may be different from those of native
      born, the experiences of immigrant victims and their satisfaction with the
      justice system are similar in many respects to those of native-born victims.

PMID- 9650244
TI  - Close relationships of violent and nonviolent African American delinquents.
AB  - One hundred and one incarcerated African American adolescent delinquents, 51
      violent and 50 nonviolent were contrasted on background variables and measures of
      close relationships. Violent delinquents were found to be older, have a greater
      number of arrests, lower reading achievement scores, and were more likely to have
      a criminal parent in the home. Violent, as compared with nonviolent delinquent,
      showed differences in close relationships. Violent delinquents were more likely
      to perceive their mothers as showing more rejection/undifferentiated behavior and
      their attachments, mainly to hetero-sexual partners, were more anxious. The
      results were interpreted in terms of both quantitative and qualitative
      distinctions between violent and nonviolent delinquents, with violent delinquents
      showing greater impairment.

PMID- 9650245
TI  - Coercive sexual strategies.
AB  - This study examines the use of coercive sexual strategies by men and the outcomes
      of these behaviour for women. Using a sample of 541 college undergraduates, data
      were gathered from men on their use of three types of coercive sexual strategies
      and from women on their experiences with these same forms of behaviors. For
      women, there is a positive association between being sexually active, having
      sexually permissive attitudes, drinking alcohol and being a victim of certain
      types of sexual coercive strategies. For men, sexually permissive attitudes and
      attitudes toward rape are found to be significant predictors of their use of
      verbal coercion. Furthermore, being a fraternity member is associated with the
      use of verbal coercion and physical force and being a sorority member is
      associated with being a victim of alcohol/drug coercion and physical force.
      Reports from both men and women give a more comprehensive interpretation of the
      specific mechanisms through which different coercive strategies are played out.

PMID- 9650246
TI  - Relationships between experiences of parental violence during childhood and
      women's self-esteem.
AB  - The interrelationships between experience of parental verbal aggression and
      physical violence during childhood and the development of low self-esteem during
      adulthood were explored separately for the father-daughter and mother-daughter
      relationships. Data were collected from 472 women between the ages of 18 and 45
      during in-depth interviews drawn from five sources: outpatient alcoholism
      treatment, DWI (Driving While Intoxicated) education programs, shelter for
      battered women, outpatient mental health treatment, and randomly from the
      community. Control variables included respondents' alcohol problems and help
      seeking behavior, parental alcohol problems, number of changes in childhood
      family (e.g., divorce), and respondents' race and social class. Controlling for
      these variables, experiences of father-to-daughter verbal aggression, moderate
      violence, and severe violence were found related to lower self-esteem in
      adulthood for women. Conversely, controlling for these variables, experiences of
      mother-to-daughter verbal aggression, moderate violence, and severe violence were
      not found related to lower self-esteem in adulthood for women.

PMID- 9650247
TI  - Follow-up of rapists treated in a forensic psychiatric hospital.
AB  - Current research examining the effectiveness of sex offender treatment is
      encouraging. Despite this optimism, research focusing on men who sexually assault
      adult women is less optimistic. This study examines the preliminary results of 74
      rapists admitted into the Phoenix program, a voluntary sex offender treatment
      program in a forensic psychiatric hospital. Patients were categorized according
      to whether they completed treatment or not. Treated rapists (n = 36) reoffended
      at a substantially lower rate than untreated rapists who were assessed but not
      treated (n = 38). Statistically significant differences in reoffense rates were
      found for violent, nonsexual offenses as well as nonviolent, nonsexual offenses.
      Although nearly twice as many treatment noncompleters reoffended sexually, the
      difference between the two groups was not statistically significant. Mean follow
      up time was well over four years for both groups. The implications of these
      findings are discussed.

PMID- 9650248
TI  - Degradation of dioxin-like compounds by microorganisms.
AB  - Polychlorinated dibenzo-p-dioxins (PCDD) and polychlorinated dibenzofurans (PCDF;
      PCDD/F, dioxins) have not been commercially produced in bulk amounts, as were
      polychlorinated biphenyls and other haloaromatic organics. Within the past two
      decades a lot of information has accumulated on the biodegradation of PCDD/F and
      other dioxin-like compounds because of their toxicity and because of significant
      environmental concern about many congeners of this class of chemicals. PCDD/F are
      subjected to reductive dehalogenations leading to less halogenated congeners,
      which can be attacked efficiently by fungal and bacterial oxidases and
      dioxygenases. In several cases these compounds can be utilized as carbon and
      energy sources. Pathways for their enzymatic degradation and the organisation of
      the corresponding degradative genes have been elucidated. Consequently,
      biotechnological applications will exploit the degradative potential of such
      microorganisms for bioremediation of contaminated sites.

PMID- 9650249
TI  - Ethanol production using nuclear petite yeast mutants.
AB  - Two respiratory-deficient nuclear petites, FY23 delta pet191 and FY23 delta
      cox5a, of the yeast Saccharomyces cerevisiae were generated using polymerase
      chain-reaction-mediated gene disruption, and their respective ethanol tolerance
      and productivity assessed and compared to those of the parental grande, FY23WT,
      and a mitochondrial petite, FY23 rho(0). Batch culture studies demonstrated that
      the parental strain was the most tolerant to exogenously added ethanol with an
      inhibition constant, Ki, of 2.3% (w/v) and a specific rate of ethanol production,
      qp, of 0.90 g ethanol g dry cells-1 h-1. FY23 rho(0) was the most sensitive to
      ethanol, exhibiting a Ki of 1.71% (w/v) and qp of 0.87 ethanol g dry cells-1 h-1.
      Analyses of the ethanol tolerance of the nuclear petites demonstrate that
      functional mitochondria are essential for maintaining tolerance to the toxin with
      the 100% respiratory-deficient nuclear petite, FY23 delta pet191, having a Ki of
      2.14% (w/v) and the 85% respiratory-deficient FY23 delta cox5a, having a Ki of
      1.94% (w/v). The retention of ethanol tolerance in the nuclear petites as
      compared to that of FY23 rho(0) is mirrored by the ethanol productivities of
      these nuclear mutants, being respectively 43% and 30% higher than that of the
      respiratory-sufficient parent strain. This demonstrates that, because of their
      respiratory deficiency, the nuclear petites are not subject to the Pasteur effect
      and so exhibit higher rates of fermentation.

PMID- 9650250
TI  - Use of azo dye ligand chromatography for the partial purification of a novel
      extracellular peroxidase from Streptomyces viridosporus T7A.
AB  - Crude peroxidase preparations from the lignocellulose-degrading actinomycete,
      Streptomyces viridosporus T7A, were shown to decolorize several azo dye isomers
      and showed a correlation of dye structure to degradability similar to that shown
      by fungal Mn-peroxidase, an enzyme not previously described in actinomycetes.
      Addition of the heme-peroxidase inhibitor KCN did not significantly change the
      ability of the T7A enzyme(s) to decompose the dyes. These results suggest that
      T7A may produce an Mn- or other peroxidase with similar substrate specificity to
      Mn-peroxidase. Affinity chromatography using immobilized azo dye isomers was used
      for purifying peroxidases from T7A. A significantly purified peroxidase
      preparation was obtained irrespective of the azo dye used. In comparison,
      concanavalin A lectin affinity chromatography showed very poor binding and
      resolution for T7A peroxidases. Azo dye affinity purification gave preparations
      sufficiently purified to allow amino acid microsequencing for two of the bound
      proteins. N-terminal amino acid sequences were found to share significant
      homology with a fungal Mn-peroxidase and actinomycete cellulases.

PMID- 9650251
TI  - Recombinant bioprocess optimization for heterologous protein production using two
      stage, cyclic fed-batch culture.
AB  - A two-stage, cyclic fed-batch bioprocess was designed, and its performance
      evaluated to improve rice alpha-amylase productivity by the yeast Yarrowia
      lipolytica SMY2 (MatA, ade1, ura3, xpr2), ATCC 201847, containing a replicative
      plasmid coding for a rice alpha-amlyase. Transcription of the recombinant gene is
      controlled by the XPR2 promoter. The first stage (or growth stage) was operated
      in the fed-batch mode, and the growth medium, designed to maintain a constant
      high cell density (i.e., 60 g/l), was fed according to a predetermined and
      preprogrammed optimal feed rate which, in turn, maintained the specific cell
      growth rate at an optimal value (i.e., 0.1 h-1). Typically, when the volume in
      the first stage reached a preset value, a portion of culture broth (i.e., 55%)
      was transferred to the second stage (or production stage). The remaining cells in
      the growth stage were then fed with fresh growth medium according to the
      bioprocess control strategy developed, while induction of alpha-amylase
      expression and its production was taking place in the second stage. The second
      stage was also operated in the fed-batch mode, and the production medium designed
      to maintain a constant high cell density and high productivity of heterologous
      protein was fed at a predetermined and preprogrammed rate, which maintained the
      specific cell growth rate at an optimal level. The volumetric alpha-amylase
      productivity achieved (1835 units l-1 h-1) from the two-stage, cyclic fed-batch
      culture process was twofold higher than that of the fed-batch culture process.
      The genetic stability of the recombinant strain and the design of optimal media
      for growth and production stages are also critically important to a successful
      implementation of the two-stage, cyclic fed-batch process for production of
      heterologous protein.

PMID- 9650252
TI  - Laccase from the white-rot fungus Trametes trogii.
AB  - The white-rot fungus Trametes trogii excretes a main laccase showing a molecular
      mass of 70 kDa, acidic isoelectric point and N-terminal sequence homologous to
      that of several phenol oxidases. The purified enzyme oxidizes a number of
      phenolic and non-phenolic compounds; recalcitrant molecules may be converted into
      substrates by introducing, in the correct position, o- or p-orienting ring
      activating groups.

PMID- 9650253
TI  - Identification of tandemly repeated type VI cellulose-binding domains in an
      endoglucanase from the aerobic soil bacterium Cellvibrio mixtus.
AB  - Cellulose-binding domains (CBD) play a pivotal role during plant cell wall
      hydrolysis by cellulases and xylanases from aerobic soil bacteria. Recently we
      have reported the molecular characterisation of a single-domain endoglucanase
      from Cellvibrio mixtus, suggesting that some cellulases produced by this aerobic
      bacterium preferentially hydrolyse soluble cellulosic substrates. Here we
      describe the complete nucleotide sequence of a second cellulase gene, celB, from
      the soil bacterium C. mixtus. It revealed an open reading frame of 1863 bp that
      encoded a polypeptide, defined as cellulase B (CelB) with a predicted Mr of 66
      039. CelB contained a glycosyl hydrolase family 5 catalytic domain at its N
      terminus followed by two repeated domains, which exhibited sequence identity with
      type VI CBD previously found in xylanases. Full-length CelB bound to cellulose
      while catalytically active truncated cellulase derivatives were unable to bind
      the polysaccharide, confirming that CelB is a modular enzyme and that the type VI
      CBD homologues were functional. Analysis of the biochemical properties of CelB
      revealed that the enzyme hydrolyses a range of cellulosic substrates, although it
      was unable to depolymerise Avicel. We propose that type VI CBD, usually found in
      xylanases, provide an additional mechanism by which cellulases can accumulate on
      the surface of the plant cell wall, although they do not potentiate cellulase
      activity directly. The results demonstrate that C. mixtus, in common with other
      aerobic bacteria, is able to produce cellulases that are directed to the
      hydrolysis of cellulose in its natural environment, the plant cell wall.

PMID- 9650254
TI  - Production of a new DNA vehicle for gene transfer using site-specific
      recombination.
AB  - Supercoiled DNA molecules, minicircles, were produced by in vivo site-specific
      recombination. They contained exclusively the desired excisable fragment.
      Recombination was driven by bacteriophage lambda integrase from a plasmid
      substrate containing the attP and attB recombination sites in the same
      orientation. Conditions for minicircle production within the lysogen Escherichia
      coli D1210HP were optimised. Up to 1.5 mg minicircles could be produced per litre
      bacterial culture, and the remaining, unrecombined plasmid comprised less than
      about 15% of the minicircle produced. However minicircle multimers were also
      produced, and comprised up to 30% of all minicircles synthesised. The par ABCDE'
      locus from plasmid RK2 was introduced into the minicircle fragment, resulting in
      minicircle dimers being reduced to less than 2% of all minicircles. The par A
      gene encodes a resolvase that catalyses recombination at the multimer resolution
      site in the parABCDE' locus. Minicircle multimers were also resolved when par A
      was introduced downstream from the integrase gene of the lambda pL transcript in
      D1210HP together with a multimer resolution site carried by the minicircle
      fragment.

PMID- 9650255
TI  - Overexpression of high-molecular-mass nitrile hydratase from Rhodococcus
      rhodochrous J1 in recombinant Rhodococcus cells.
AB  - High-molecular-mass nitrile hydratase (H-NHase, 530 kDa) is a cobalt-containing
      enzyme produced by Rhodococcus rhodochrous J1. For efficient production of H
      NHase in R. rhodochrous ATCC12674, several plasmids were constructed. The enzyme
      was produced in the recombinant Rhodococcus cells only in the presence of an
      upstream region (approximately 4 kb) of the H-NHase gene under the control of the
      promoter for the amidase-NHase gene cluster from Rhodococcus sp. N-774. Although
      H-NHase was produced as a soluble protein in the cells, the protein did not show
      NHase activity. However, when the recombinant R. rhodochrous ATCC12674 cells were
      cultured in the presence of amide compounds, such as crotonamide and
      methacrylamide, markedly high NHase activity was detected, Gel-filtration
      chromatography revealed that the NHases produced by the cells grown in the
      presence and absence of the amide compounds had a molecular mass of more than 500
      kDa and 50-80 kDa respectively. These results suggest that the amide compounds
      are essential for subunit assembly to form an enzymatically active multimer. By
      the use of the recombinant expression system, NHase activity 1.7 times higher
      than that of the original strain, R. rhodochrous J1, was achieved.

PMID- 9650256
TI  - Phosphate-independent expression of the carbon-phosphorus lyase activity of
      Escherichia coli.
AB  - On the basis of mutational analysis, the genes for phosphonate uptake and
      degradation in Escherichia coli were shown to be organized in a 10.9-kb operon of
      14 genes (named phnC to phnP) and induced by phosphate (P(i)) starvation [Metcalf
      and Wanner (1993) J Bacteriol 175: 3430-3442]. The repression of phosphonate
      utilization by P(i) has hindered both the biochemical characterization of the
      carbon-phosphorus (C-P) lyase activity and the development of improved methods
      for phosphonate biodegradation in biotechnology. We have cloned the genes phnG to
      phnP (associated with C-P lyase activity) with the lac promoter to provide
      expression of C-P lyase in the presence of P(i). A number of strains lacking
      portions of the phn operon have been constructed. In vivo complementation of the
      strains, in which phnC to phnP (including both Pn transport and catalysis genes)
      or phnH to phnP (including only catalysis genes) was deleted, with plasmids
      carrying various fragments of the phn operon revealed that the expression of phnC
      phnP gene products is essential to restore growth on minimal medium with
      phosphonate as the sole phosphorus source, while phnG-phnM gene products are
      required for C-P lyase activity as assessed by in vivo methane production from
      methylphosphonic acid. The minimum size of the DNA required for the whole-cell C
      P lyase activity has been determined to be a 5.8-kb fragment, encompassing the
      phnG to phnM genes. Therefore, there is no requirement for the phn CDE-encoded
      phosphate transport system, suggesting that cleavage of the C-P bond may occur on
      the outer surface of the inner membrane of E. coli cells, releasing the carbon
      moiety into the periplasm. These data are in agreement with the observation that
      phosphonates cannot serve as the carbon source for E. coli growth.

PMID- 9650257
TI  - The effects of space flight on the production of monorden by Humicola fuscoatra
      WC5157 in solid-state fermentation.
AB  - The effect of space flight on the production of the antibiotic monorden on two
      types of agar media, T8 and PG, by Humicola fuscoatra WC5157 was examined on
      board the US Space Shuttle mission STS-77 in May 1996. Paired space-flight and
      ground control samples were prepared using identical hardware, protocol, media,
      and inoculum. Inoculation occurred simultaneously for both groups 2.5 after
      launch. The flight and ground samples were allowed to grow for the entire 10-day
      mission in a dark, thermally controlled (22 degrees C) environment. Post-flight
      HPLC analysis of the flight and ground sample extracts indicated that the
      production of monorden by H. fuscoatra WC5157 in the flight samples was higher
      than in the ground samples in both agar media. In the T8 medium, the production
      of monorden in the flight and ground samples was 11.6 +/- 3.5 micrograms and 8.9
      +/- 1.1 micrograms respectively (30% increase). In the PG medium, the production
      of monorden in the flight and ground samples was 23.8 +/- 3.3 micrograms and 8.2
      +/- 2.2 micrograms respectively (190% increase). The production of monorden in
      the flight and ground control samples was confirmed by HPLC-MS analysis.

PMID- 9650258
TI  - The diversion of lactose carbon through the tagatose pathway reduces the
      intracellular fructose 1,6-bisphosphate and growth rate of Streptococcus bovis.
AB  - Twenty strains of Streptococcus bovis grew more slowly on lactose (1.21 +/- 0.12
      h-1) then than on glucose (1.67 +/- 0.12 h-1), and repeated transfers or
      prolonged growth in continuous culture (more than 200 generations each) did not
      enhance the growth rate on lactose. Lactose transport activity was poorly
      correlated with growth rate, and slow growth could not be explained by the ATP
      production rate (catabolic rate). Batch cultures growing on lactose always had
      less intracellular fructose 1,6-bisphosphate (Frul,6P2) than cells growing on
      glucose (6.6 mM compared to 16.7 mM), and this difference could be explained by
      the pathway of carbon metabolism. Glucose and the glucose moiety of lactose were
      metabolized by the Embden-Meyerhoff-Parnas (EMP) pathway, but the galactose
      moiety of lactose was catabolized by the tagatose pathway, a scheme that by
      passed Frul,6P2. A mutant capable of co-metabolizing lactose and glucose grew
      more rapidly when glucose was added, even though the total rate of hexose
      fermentation did not change. Wild-type S. bovis grew rapidly with galactose and
      melibiose, but these galactose-containing sugars were activated by galactokinase
      and catabolized via EMP. On the basis of these results, rapid glycolytic flux
      through the EMP pathway is needed for the rapid growth (more than 1.2 h-1) of S.
      bovis.

PMID- 9650259
TI  - Isolation and characterization of two bacteriocins of Lactobacillus acidophilus
      LF221.
AB  - Lactobacillus acidophilus LF221 produced bacteriocin-like activity against
      different bacteria including some pathogenic and food-spoilage species. Besides
      some lactic acid bacteria, the following species were inhibited: Bacillus cereus,
      Clostridium sp., Listeria innocua, Staphylococcus aureus, Streptococcus D. L.
      acidophilus LF221 produced at least two bacteriocins, acidocin LF221 A and
      acidocin LF221 B, which were purified by ammonium sulphate precipitation, ion
      exchange chromatography, hydrophobic interaction and reverse-phase FPLC. The
      antibacterial substances were heat-stable, sensitive to proteolytic enzymes
      (trypsin, pepsin, pronase, proteinase K) and migrated as 3500- to 5000-Da
      proteins on sodium dodecyl sulphate/polyacrylamide gel electrophoresis. The
      sequences of 46 amino-terminal amino acid residues of peptide A and 35 of peptide
      B were determined. Among the residues identified, no modified amino acids were
      found. No significant homology was found between the amino acid sequences of
      acidocin LF221 A and other bacteriocins of lactic acid bacteria and 26% homology
      was found between acidocin LF221 B and brevicin 27. L. acidophilus LF221 may be
      of interest as a probiotic strain because of its human origin and inhibition of
      pathogenic bacteria, especially clostridium difficile.

PMID- 9650260
TI  - Biodegradation of atrazine under denitrifying conditions.
AB  - Anaerobic biodegradation of atrazine by the bacterial isolate M91-3 was
      characterized with respect to mineralization, metabolite formation, and
      denitrification. The ability of the isolate to enhance atrazine biodegradation in
      anaerobic sediment slurries was also investigated. The organism utilized atrazine
      as its sole source of carbon and nitrogen under anoxic conditions in fixed-film
      (glass beads) batch column systems. Results of HPLC and TLC radiochromatography
      suggest that anaerobic biotransformation of atrazine by microbial isolate M91-3
      involved hydroxyatrazine formation. Ring cleavage was demonstrated by 14CO2
      evolution. Denitrification was confirmed by detection of 15N2 in headspace
      samples of K15NO3-amended anaerobic liquid cultures. In aquatic sediments,
      mineralization of uniformly ring-labeled [14C]atrazine occurred in both M91-3
      inoculated and uninoculated sediment. Inoculation of sediments with M91-3 did not
      significantly enhance anaerobic mineralization of atrazine as compared to
      uninoculated sediment, which suggests the presence of indigenous organisms
      capable of anaerobic atrazine biodegradation. Results of this study suggest that
      the use of M91-3 in a fixed-film bioreactor may have applications in the
      anaerobic removal of atrazine and nitrate from aqueous media.

PMID- 9650261
TI  - Rapid atrazine mineralisation in soil slurry and moist soil by inoculation of an
      atrazine-degrading Pseudomonas sp. strain.
AB  - The evaluation of pesticide-mineralising microorganisms to clean-up contaminated
      soils was studied with the widely applied and easily detectable compound
      atrazine, which is rapidly mineralised by several microorganisms including the
      Pseudomonas sp. strain Yaya 6. The rate of atrazine removal was proportional to
      the water content of the soil and the amount of bacteria added to the soil. In
      soil slurry, 6 mg atrazine kg soil-1 was eliminated within 1 day after
      application of 0.3 g dry weight inoculant biomass kg soil-1 and within 5 days
      when 0.003 g kg soil-1 was used. In partially saturated soil (60% of the maximal
      water-holding capacity) 15 mg atrazine kg soil-1 was used. In unsaturated soil,
      about 60% [U-ring-14C] atrazine was converted to 14CO2 within 14 days. Atrazine
      was very efficiently removed by the inoculant biomass, not only in soil that was
      freshly contaminated but also in soil aged with atrazine for up to 260 days. The
      bacteria exposed to atrazine in unsaturated sterile soil were still active after
      starvation period of 240 days: 15 mg newly added atrazine kg soil-1 was
      eliminated within 5 days.

PMID- 9650262
TI  - A review of radiologically important trace elements in human bones.
AB  - The authors recently compiled and reviewed the literature for minor and trace
      elements in human bones and teeth as a part of an International Atomic Energy
      Agency (IAEA) study. Various aspects of elemental composition, analytical
      methodologies, quality assurance and quality control methods for hard tissue
      analysis were evaluated. Important data on selected radiologically important
      elements (Cs, Pu, Ra, Sr, Th, and U) in calcified tissue from various countries
      are discussed. The results of this compilation study suggest a need for new
      reference materials with matrix properties similar to bones including one with
      separated cortical and trabecular segments.

PMID- 9650263
TI  - An investigation of the imaging characteristics of the Y2O2S:Eu3+ phosphor for
      application in X-ray detectors of digital mammography.
AB  - Y2O2S:Eu laboratory prepared screens were evaluated as mammographic image
      receptors and were compared to similarly prepared screens of Gd2O2S:Tb and
      Y2O2S:Tb phosphor materials, often used in X-ray imaging detectors. The
      evaluation was performed by determining the Modulation Transfer Function (MTF)
      and the spatial frequency dependent Detective Quantum Efficiency (DQE). Y2O2S:Eu
      exhibited higher DQE values at low frequencies and given its good spectral
      matching with digital optical detectors, it may be appropriate for use in X-ray
      digital mammography.

PMID- 9650264
TI  - Cytotoxicity and mutagenicity of a 2,4,6-trinitrotoluene (TNT) and hexogen
      contaminated soil in S. typhimurium and mammalian cells.
AB  - The toxicity and mutagenicity of aqueous and organic extracts of soil
      contaminated with TNT, TNT metabolites and hexogen was determined in mammalian
      cell lines and in prokaryotic cells. The prokaryotic toxicity was determined via
      the colony forming ability of Salmonella typhimurium (strains TA 98 and TA 100).
      The same strains were used to test mutagenicity in the Ames test. The mammalian
      toxicity was analyzed in human fibroblasts by the inhibition of cell growth and
      cell viability (MTT assay). The mammalian mutagenicity was tested with the HPRT
      test in V79 cells (hamster lung). The aqueous soil extract did not reveal
      toxicity or mutagenicity in any of the tests performed. The DMSO/ethanol extract
      showed toxicity and mutagenicity in S. typhimurium. Thereby strain TA 98 was more
      sensitive than strain TA 100. In human fibroblasts cell growth was strongly
      inhibited, whereas no reduction of cell viability was found in the MTT test.
      Mutagenicity of the DMSO/ethanol extract of the soil was demonstrated in V79
      cells.

PMID- 9650265
TI  - Identification of lipophilic pollutants discharged from a Finnish pulp and paper
      mill.
AB  - Lipophilic organic compounds originating from kraft pulping and papermaking were
      identified by straight gas chromatography/mass spectrometry (GC/MS) analyses.
      Samples analyzed included a primary clarifier effluent (PE) and a secondary
      clarifier effluent (SE) from the activated sludge treatment plant of a Finnish
      ECF-bleached (Elementally Chlorine Free) kraft pulp and paper mill. Liquid-liquid
      extraction composition of PE was compared with solid phase extraction (SPE) and
      dialysis of a semipermeable membrane device (SPMD) exposed to PE. Dichloromethane
      extracts of particulate material isolated from PE, sludges from both the primary
      and secondary clarifier, a sediment collected in the vicinity of the mill and
      whitefish subacutely exposed to the secondary treatment effluent were also
      investigated. Typical pulp mill-related compounds such as terpenes, terpenoids
      and aromatic compounds were identified in PE whereas these were non-detectable in
      SE. For example, thunbergene, thunbergol, squalene, longifolene and derivatives
      of abietic acid were observed in PE. Alkylated polycyclic aromatics were major
      compounds identified in the sediment sample with retene (C4-alkyl phenanthrene)
      as a predominant component.

PMID- 9650266
TI  - Kinetics of biodegradation of di-n-butyl phthalate in continuous culture system.
AB  - The characteristics of microbial growth and kinetics of DBP biodegradation was
      studied in a continuous culture system using DBP as a sole source of carbon. The
      results showed that, at high substrate concentration, the microbial growth was
      inhibited by DBP, and can be described by the Haldane model. Kinetic parameters
      based on Haldane substrate inhibition were evaluated. The values were mu(m) =
      0.38 h-1, Ki = 86 mg/l, Ks = 28 mg/l. The DBP concentration to avoid substrate
      inhibition was inferred theoretically and determined to be 49 mg/L.

PMID- 9650267
TI  - The efficiency of different phenol-degrading bacteria and activated sludges in
      detoxification of phenolic leachates.
AB  - Phenolic composition, toxicity and biodegradability of three different phenolic
      leachates/samples was studied. Samples A and C were the leachates from the oil
      shale industry spent shale dumps at Kohtla-Jarve, Estonia. Sample B was a
      laboratory-prepared synthetic mixture of 7 phenolic compounds mimmicking the
      phenolic composition of the leachate A. Toxicity of these 3 samples was analyzed
      using two photobacterial test (BioTox and Microtox), Daphnia test (DAPHTOXKIT F
      pulex) and rotifiers' test (ROTOXKIT F). All the LC50 values were in the range of
      1-10%, leachate A being the most toxic. The growth and detoxifying potential
      (toxicity of the growth medium was measured using photobacterial tests) of 3
      different phenol-utilizing bacteria and acclimated activated sludges was studied
      in shake-flask cultures. 30% leachate A (altogether 0.6 mM total phenolic
      compounds) was too toxic to rhodococci and they did not grow. Cell number of
      Kurthia sp. and Pseudomonas sp. in 30% leachate A increased by 2 orders of
      magnitude but despite of the growth of bacteria the toxicity of the leachate did
      not decrease even by 7 weeks of cultivation. However, if the activated sludge was
      used instead of pure bacterial cultures the toxicity of the 30% leachate A was
      eliminated already after 3 days of incubation. 30% samples B and C were
      detoxified by activated sludge even more rapidly, within 2 days. As the
      biodegradable part of samples A and B should be identical, the detoxification of
      leachate A compared to that of sample B was most probably inhibited by inorganic
      (e.g. sulphuric) compounds present in the leachate A. Also, the presence of toxic
      recalcitrant organic compounds in the leachate A (missed by chemical analysis)
      that were not readily biodegradable even by activated sludge consortium should
      not be excluded.

PMID- 9650268
TI  - The 'two-phase closed bottle test'--a suitable method for the determination of
      'ready biodegradability' of poorly soluble compounds.
AB  - The Two-Phase Closed Bottle test (BODIS test) is a cost-effective supplement of
      the existing OECD tests for ready biodegradability (OECD 301) due to its entire
      compatibility with them and its particular suitability for testing poorly soluble
      compounds. The comparison of a number of test data from this and other ready
      biodegradability tests showed that the BODIS test has a similar stringency in
      terms of the attainment of the pass level and the time window criterion as well.
      A significant influence of the strength of the bacterial inoculum on the test
      results was not observed.

PMID- 9650269
TI  - Uptake of moderately hydrophobic chlorophenols from water by semipermeable
      membrane devices (SPMDs) and by goldfish (Crassius auratus).
AB  - Semipermeable membrane devices (SPMDs) filled with triolein and goldfish
      (Crassius auratus) were simultaneously exposed to nine moderately hydrophobic
      chlorophenols in a laboratory continuous-flow experiment. The results showed that
      the test compounds were concentrated in the device to an extent very closed to
      that in fish. The overall uptake rate constants (Ku) and average pollutant
      sampling rates (Rs) were similar for both SPMDs and goldfish. We conclude that
      the SPMDs can be used to estimate the levels of moderately hydrophobic
      chlorophenols in field water as an environmental monitor.

PMID- 9650270
TI  - Environmental biotechnology regulatory affairs. Web alert.

PMID- 9650271
TI  - Molecular genetics of bacterial attachment and biofouling.
AB  - Microbial adhesion to animate or inert surfaces is potentially mediated by
      nonspecific physical or specific ligand-receptor interactions. Growth and
      survival of the microbial community or biofilm then depends on adaptation to a
      series of changing environmental milieux. Within the realm of cell-cell
      interaction, recent advances suggest that flagella, fimbriae and other protein
      receptors are essential for bacterial attachment to surfaces. There has also been
      profound progress in the elucidation of genes and molecules necessary for
      bacterial attachments to surfaces and subsequent biofilm formation.

PMID- 9650272
TI  - The molecular biology of chitin digestion.
AB  - Chitinases catalyze the hydrolysis of chitin, an unbranched polymer of beta-1,4-N
      acetylglucosamine. In recent years, soil-borne microorganisms that produce
      chitinases are considered as potential biocontrol agents against fungi and
      nematodes which causes diseases of agricultural crops. Chitinases also play an
      important physiological and ecological role in ecosystems as recyclers of chitin,
      by generating carbon and nitrogen sources. Many chitinases of varied organisms
      have been isolated and their corresponding genes cloned.

PMID- 9650273
TI  - Bioenergetics of marine bacteria.
AB  - Some marine bacteria have a special energy-transducing mechanism that is
      different from those found in Escherichia coli or most of the freshwater and
      terrestrial bacteria. These marine bacteria specifically require Na+ for their
      growth and utilize a Na+ circuit for various cellular functions. So far, three
      types of primary Na+ pump have been identified (i.e. respiration-dependent,
      decarboxylase-driven and Na+ ATP synthase). Among them, the first type of Na+
      pump plays the major role in the marine environment. Recently, the gene sequence
      and distribution of this Na+ pump have been clarified. In addition, information
      on genetics and the ecological significance of Na+ driven flagellar motors has
      also been accumulating. This recent progress in the research of the 'Na+ world'
      is revealing an interesting way of life that is unique to marine microorganisms.

PMID- 9650274
TI  - Molecular approaches to measuring microbial marine pollution.
AB  - Developments in the rapid detection of pathogens (PCR and its variations) and
      molecular typing of strains isolated from the ecosystem illustrate the
      stimulation of research due to the recent foodborne and waterborne disease
      outbreaks.

PMID- 9650275
TI  - Strengthening the biological weapons convention and implications on the
      pharmaceutical and biotechnology industry.
AB  - The development, production, stockpiling, and use of biological weapons are
      banned by the 1972 Biological Weapons Convention (BWC). Reflecting the realities
      of the Cold War era in which it was negotiated, the BWC lacks means for
      compliance verification or enforcement. International efforts to remedy this
      deficiency are accelerating in the face of evidence that covert biological weapon
      programs are proliferating at the national and subnational levels.

PMID- 9650276
TI  - Specifications for biotechnology-derived protein drugs.
AB  - Specifications are the regulatory and legal standards that a product must meet to
      be suitable for use in humans. Specifications evolve in parallel with drug
      development and are refined prior to marketing authorization and, in some cases,
      after marketing. Recent changes in regulatory procedures for biotechnology
      derived protein products have placed much emphasis on the use of characterization
      and final product specifications to provide assurance of overall quality of these
      products. In addition, harmonized guidelines for the testing and specifications
      for biotechnology products have been developed through the International
      Conference on Harmonization process. The availability of sensitive, quantitative,
      and specific analytical methods for characterization has made this possible, thus
      providing regulatory flexibility in the development of biotechnology-derived
      protein products. Further refinement of these analytical tools will undoubtedly
      enhance this regulatory flexibility.

PMID- 9650277
TI  - Heterozygosity-fitness correlations: new perspectives on old problems.
AB  - Heterozygosity-fitness correlations (HFC) have been studied in various organisms
      for more than two decades, but they are not universal. Although their
      detectability is limited by several factors (null alleles, inaccuracy of the
      phenotypic description of fitness, small sample sizes) the correlations appear
      intrinsically weak and often inconsistent across samples. Determining the origins
      of HFC is therefore a complex task. However, this issue might soon be resolved
      provided clear hypotheses and definitions are used (especially, if the problem of
      the neutrality of allozyme variation is not identified with the related issue of
      HFC), as well as new empirical (molecular markers) & theoretical (statistical
      models) tools.

PMID- 9650278
TI  - Gene conversion disparity in yeast: its extent, multiple origins, and effects on
      allele frequencies.
AB  - The extent of disparity in gene conversion direction in yeast (Saccharomyces
      cerevisiae) is important for recombination mechanisms and for effects of
      conversion on allele frequencies in populations. An analysis of published and
      unpublished data demonstrates that yeast frequently shows significant and
      extensive conversion disparity, contrary to many published statements. All types
      of mutation--base-substitutions, frameshifts and longer deletions and additions-
      can show significant 6:2/2:6 and/or 5:3/3:5 disparity. There was little
      correlation between the occurrence of 6:2/2:6 and 5:3/3:5 disparities; when both
      were significant, they were more often in opposite directions than in the same
      direction. Surprisingly, there was little correlation between a mutation's
      molecular nature and its disparity properties, which generally seem
      unpredictable. Disparity in yeast has multiple origins. From the equations
      discussed, all disparity types can be explained by one or more of: correction
      direction disparity, chromatid invasion disparity (including cases caused by
      different frequencies of double-strand breaks or gaps in nonsister homologous
      chromatids), strand invasion disparity, and different correction frequencies for
      the two types of mispair for a heterozygous mutation. Levels of overall disparity
      and of conversion frequency mean that conversion must often change allele
      frequencies in sexually reproducing yeast populations.

PMID- 9650279
TI  - Chloroplast DNA recognizes three refugial sources of European oaks and suggests
      independent eastern and western immigrations to Finland.
AB  - Refugial differentiation and routes of postglacial migration are major
      determinants of the patterns of geographical variation we see in natural
      populations today. We used patterns of chloroplast DNA (cpDNA) variation to
      investigate the postglacial colonization history of the European oak species
      Quercus robur and Q. petraea. By sequencing two cpDNA segments using universal
      primers, we revealed four polymorphic sites which identify four cytotypes with
      characteristic geographical distributions. Of these, the principal eastern,
      central and western cytotypes divide the range into three longitudinal zones,
      each extending from the south to the north of Europe. This corroborates the idea
      that the postglacial colonization started from three distinct southerly refugia.
      The fourth cytotype, restricted to East Anglia, was probably derived from the
      western type postglacially. As a special problem, we addressed the controversial
      origin of Q. robur at its northern limits in south-western Finland, where it
      currently occupies a narrow coastal zone disjunct from the remaining oak range.
      Using a PCR-RFLP assay that discriminates the eastern cytotype, a contact zone of
      two cytotypes was identified in the region of the Salpausselka ridges. This
      suggests that the marginal northern occurrence was independently colonized both
      from the east and from the west, across the Baltic Sea.

PMID- 9650280
TI  - Genetic relationships within the genus Beta determined using both PCR-based
      marker and DNA sequencing techniques.
AB  - The sequences of ITS1 of the internal transcribed spacer regions of nuclear
      ribosomal DNA from 11 species or subspecies in four sections of the genus Beta
      were compared. Phylogeny of these wild beet taxa was inferred from the sequence
      data using phenetic and phylogenetic analyses. Multiple accessions from the same
      11 taxa were subjected to random amplified polymorphic DNA (RAPD) analysis, and
      the data were analysed phenetically. With both molecular techniques and each
      analysis, three distinctive groups were formed: species from section Beta formed
      one group; species from section Procumbentes formed a very distinct group; and
      species from both section Nanae and section Corollinae clustered together forming
      the third group, which is closer to Beta than Procumbentes. The RAPD data
      revealed within-section interspecies relationships that are consistent with those
      reported previously; this was not always the case using the single-locus sequence
      data.

PMID- 9650281
TI  - mtDNA phylogeography and postglacial patterns of subdivision in the meadow
      grasshopper Chorthippus parallelus.
AB  - A 300 bp portion of the mitochondrial cytochrome oxidase subunit I (COI) gene was
      used to investigate the intraspecific genetic structure of the European meadow
      grasshopper Chorthippus parallelus. Levels of genetic subdivision between
      geographical regions in Europe were assessed using the KST statistic and revealed
      patterns indicative of the postglacial history of this organism. Northern
      European populations are shown to share a very recent common ancestor with, and
      hence originate from, a Balkan expansion. Genetic distances between these areas
      and both southern Italy and central Spain are shown to be approximately equal,
      even though only the Spanish form is recognized as a distinct subspecies.
      Distance estimates indicate that the common ancestor of the two subspecies lived
      more than one glacial cycle ago, and the refugial populations have probably been
      diverging in isolation for five or six glacial cycles (approximately equal to
      550,000 years). Comparisons are made to the analysis of a similar data set using
      an anonymous nuclear DNA marker (Cooper et al., 1995). Although the structure
      revealed is generally very similar, differences in the location of transition
      zones between different genetic forms of C. parallelus may reflect the different
      historical assortment of these molecules.

PMID- 9650282
TI  - Inheritance of behavioural differences between two interfertile, sympatric
      species, Drosophila silvestris and D. heteroneura.
AB  - The Hawaiian fly species, Drosophila silvestris and D. heteroneura, are sympatric
      and interfertile but show strong behavioural isolation and major differences in
      male aggressive behaviour and the associated morphology. As a first step in
      elucidating the genetic control of the differences between these species, we
      examined the mating and aggressive behaviour of their reciprocal F1 hybrids. The
      latency to the first wing vibration and the latency to copulate did not differ
      significantly between the parental species. However, D. heteroneura females had a
      very low tendency to copulate with D. silvestris males, rarely mating during the
      observation period. The duration of copulation also differed significantly; same
      species pairs of D. silvestris had copulations that lasted about 50% longer than
      those of same-species pairs of D. heteroneura. The hybrids were intermediate
      between the parental species for both the tendency to copulate with D. silvestris
      males and the duration of copulation, suggesting codominance or polygenic
      inheritance for those traits. The aggression traits that we scored were the leg
      posture and wing extension during early aggression, and the leg posture and head
      position during escalated aggression. The parental species showed clear
      differences for each of these traits. The F1 hybrids resembled one parent or the
      other, without showing intermediate values, suggesting single-gene dominance or
      threshold expression of many genes for those traits. None of the courtship or
      aggressive traits showed X-chromosomal effects, although the head shape of
      hybrids is influenced by genes on the X chromosome. It is difficult to reconcile
      the patterns of inheritance of aggressive behaviour and the lack of an X
      chromosomal effect with the hypothesis that these traits are influenced by a
      coadapted gene complex.

PMID- 9650283
TI  - Substrate-dependent enantioselectivity of a novel hydantoinase from Arthrobacter
      aurescens DSM 3745: purification and characterization as new member of cyclic
      amidases.
AB  - A hydantoinase from Arthrobacter aurescens DSM 3745 has been purified to
      homogeneity with a yield of 77% using a three-step purification procedure. The
      active enzyme is a tetramer consisting of four identical subunits, each with a
      molecular mass of 49670 Da as determined by mass spectrometry. The N-terminal
      amino acid sequence of the enzyme indicates sequence identities to cyclic
      amidases involved in the nucleotide metabolism as the D-hydantoinase from
      Agrobacterium radiobacter (53%), the D-selective dihydropyrimidinase from
      Bacillus stearothermophilus (38%), the allantoinase from Rana catesbeiana (26%),
      as well as to the catalytic subunit of the urease from Helicobacter pylori (50%).
      However, all studies based on substrate-dependent growth, induction and catalytic
      behavior documented the novelty of the bacterial hydantoinase and that its
      physiological role is not related to any of these enzymes or known metabolic
      pathways. Its substrate specificity differs from hydantoinases listed in Enzyme
      Nomenclature and is rather more predominant for the cleavage of aryl- than for
      alkyl-hydantoin derivatives. It is shown that the stereoselectivity of this
      enzyme depends on the substrate used for bioconversion: although it is strictly L
      selective for the cleavage of D,L-5-indolylmethylhydantoin, it appears to be D
      selective for the hydrolysis of D,L-methylthioethylhydantoin. Due to these
      findings we conclude that this novel bacterial hydantoinase should be classified
      as a new member of the EC-group 3.5.2 of cyclic amidases.

PMID- 9650284
TI  - Effect of the dilution rate on the mode of oscillation in continuous cultures of
      Saccharomyces cerevisiae.
AB  - The growth properties of the asymmetric budding yeast Saccharomyces cerevisiae
      were analysed during spontaneous oscillations in continuous cultures at varying
      dilution rates D. The length of the oscillation period changed between 1.4 and 14
      h in response to the decrease of dilution rate from 0.15 to 0.05 h-1. The
      distribution of parent and daughter cells in the population was determined
      microscopically after staining the bud scars and DNA. Most of the data obtained
      fits a theoretical population balance model assuming two-classes of
      subpopulations and integer ratios between the generation times of both classes.
      Some data has to be described by an extended population model assuming there is
      one parent and two daughter cell classes. How changes of dilution rate may cause
      an accidental switch of the mode of oscillation is demonstrated. Glucose
      consumption and metabolite production were measured off-line by enzymatic methods
      and gas exchange was monitored on-line. All these data of one period point to
      internal and external signals responsible for the synchronisation of the cell
      cycle.

PMID- 9650285
TI  - Subcellular localization of enzyme activities in chemostat-grown murine myeloma
      cells.
AB  - As part of the development of structured models for the metabolism of myeloma
      cells in suspension culture, a study was made of the subcellular localization of
      key enzymes of glucose and glutamine metabolism. Steady state chemostat cultures
      of the mouse myeloma SP2/0-Ag14 were used as a reproducible source of biomass.
      Homogenates of the cells, obtained via mechanical disruption, were separated into
      a mitochondrial and a cytosolic fraction via differential centrifugation. The
      following conclusions are drawn: (1) approximately one fifth of the hexokinase
      activity of cell-free homogenates is associated with the mitochondria; (2) a
      malate-aspartate shuttle may operate for oxidation of cytosolic NADH, as
      indicated by high levels of malate dehydrogenase and aspartate aminotransferase
      in both particulate and soluble fractions; (3) the pentose phosphate pathway and
      isocitrate dehydrogenase may contribute to the provision of cytosolic NADPH; (4)
      phosphoenolpyruvate carboxykinase and pyruvate kinase, which are present in high
      activities, are exclusively cytosolic and probably play a key role in glutamine
      metabolism; (5) oxidation of glutamine via these enzymes leads to the formation
      of pyruvate that enters the same pool as pyruvate generated by glycolysis. As a
      result, lactate and alanine formation can occur from both glucose and glutamine.

PMID- 9650286
TI  - Expression in Saccharomyces cerevisiae of antigenically and enzymatically active
      recombinant glutamic acid decarboxylase.
AB  - Glutamic acid decarboxylase (GAD) is one of the major autoantigens found in
      insulin-dependent (Type 1) diabetes mellitus (IDDM). A novel hybrid form of GAD
      was created by fusing amino acids 1-101 of the human GAD67 protein to amino acids
      96-585 of the human GAD65 protein. This hybrid GAD67/65 was expressed
      constitutively under the control of the phosphoglycerate kinase promoter (PGK1)
      in the yeast Saccharomyces cerevisiae. Enzymatically active GAD was prepared from
      yeast lysates by a one-step purification on an affinity column using GAD-1
      antibody. The purified hybrid GAD67/65 was radiolabelled with iodine-125 and
      tested in an immunoprecipitation assay with IDDM sera. Results obtained using the
      recombinant yeast hybrid GAD67/65 were very similar to those obtained using 125I
      labelled porcine GAD. Recombinant yeast hybrid GAD67/65 should have utility for
      diagnosis and presymptomatic detection of IDDM.

PMID- 9650287
TI  - Review of ionic models of vagal-cardiac pacemaker control.
AB  - Mathematical models of ion currents in pacemaker cells of the heart and their
      associated modulation by vagal stimulation have provided numerous insights into
      the ionic mechanisms underlying parasympathetic control of heart rate. In this
      article, ionic models described in the literature are reviewed and compared, with
      a view to examining their effectiveness in reproducing known chronotropic
      responses to vagal stimulation.

PMID- 9650288
TI  - Modelling the dynamics of LCMV infection in mice: conventional and exhaustive CTL
      responses.
AB  - Lymphocytic choriomeningitis virus (LCMV) infection in mice provides an example
      of an extraordinarily dynamic process with an extreme sensitivity of phenotype of
      infection to parameters of virus/host interaction. A mathematical model is
      developed to examine the dynamics of virus-specific cytotoxic T lymphocyte (CTL)
      response for LCMV infection in mice. The model, formulated by a system of
      nonlinear delay-differential equations, considers the interacting populations of
      viruses, precursor CTLs, terminally differentiated effector CTLs and total virus
      antigen load. Clonal elimination of virus-specific cytotoxic T cells in high-dose
      LCMV-Docile infection represents an example of the classical phenomenon--high
      zone tolerance. To describe both conventional and exhaustive CTL responses in the
      acute phase of LCMV-D infection two mechanisms are invoked: the high virus
      antigen load inhibition of T-cells proliferation via energy induction and the
      activation-induced cell death by apoptosis. Parameters of the model,
      characterizing the rates of virus and CTL production and elimination in spleen,
      are estimated by assimilating with the model data on the LCMV-D infection in
      C57BL/6 mice for low-, moderate- and high-dose infections. It is suggested that
      not only the clonal expansions have to be described in mathematical models as
      being virus regulated but also the later phases of primary immune response. Down
      regulation of the primary CTL response is controlled by a network of mechanisms
      inducing anergy and apoptosis in activated T cells. The model is used to
      investigate the effect of variations in virus and CTL response parameters on LCMV
      infection outcome and suggest predictions for experimental studies, in particular
      the phenotype of LCMV-WE infection in C57BL/6 as a function of initial virus
      doses.

PMID- 9650289
TI  - Evolution of the immune repertoire with and without somatic DNA recombination.
AB  - Repertoire of an immune system is a set of antigen receptors each having a unique
      specificity to bind an antigen. In many vertebrate species, antigen receptors are
      produced via combinatorial arrangements of DNA segments in specialized immune
      cells. Due to this molecular mechanism, repertoire of vertebrate species is
      potentially very large. The diversity of repertoire is thought to guarantee
      recognition of most ill-causing micro-organisms. In vertebrate species however,
      similar editing of DNA segments has not been demonstrated to take place. Immune
      system of invertebrate species therefore seems to operate in a distinct manner
      from that of vertebrate species. Using an evolutionary model in which organisms
      struggle to fight infections, we attempt to understand why some species use a
      more diverse set of antigen receptors than others. Individuals in our model
      either use somatic DNA recombination to produce antigen receptors (as in
      vertebrates) or do not use such a mechanism (as in vertebrates). We found that
      individuals having an invertebrate-like immune system came to employ only a few
      antigen receptors to recognize a set of pathogens whereas those with a vertebrate
      like immune system use a larger set of more specific antigen receptors to
      recognize the same set of pathogens. Our interpretation of this finding is that
      because the genetics of the immune system imposed different constraints on the
      evolutionary process, two distinct recognition strategies have been adapted by
      these species.

PMID- 9650290
TI  - Analysis of a reduced model of corticotroph action potentials.
AB  - We have previously described a model for corticotroph plasma membrane
      electrophysiology [LeBeau et al. (1997). Biophysical Journal 73, 1263-1275]. The
      model is a Hodgkin-Huxley-like formalism consisting of six coupled ordinary
      differential equations. Analysis of this model showed that Ca2+ action potentials
      could be induced by an increase in the L-type voltage-sensitive Ca2+ current.
      Thus we have demonstrated a putative causal link between an increase in the
      corticotroph Ca2+ current and action potential generation. We report here the
      reduction of the model to one with three equations, the behaviour of which was
      found to correspond well with that of the full model. The reduced model was then
      subjected to fast-slow subsystem analysis, which revealed the mechanistic
      interaction between the membrane potential and intracellular Ca2+ concentration
      that underlies action potential generation. Insights obtained from this analysis
      were used to investigate experimentally observed aspects of corticotroph
      electrophysiology such as spontaneous electrical activity, bursting action
      potentials, and observations from anode break excitation experiments.

PMID- 9650291
TI  - Host spatial heterogeneity and extinction of an SIS epidemic.
AB  - Spatially explicit epidemic models explore population-level consequences of
      interactions between neighboring infectious and susceptible individuals. Most
      such models equate local and global host density, so that each individual
      interacts with the same number of neighbors. But many natural populations exhibit
      heterogeneity in local abundance. Therefore, we let host dispersion vary from
      uniform to clumped in a spatial epidemic with recovery. We analytically
      approximated the epidemic with a branching process to show how the probability of
      pathogen extinction could depend on the degree of host clumping. We then
      simulated the detailed model across a range of parameter combinations. Both
      approaches to the problem indicate that host spatial aggregation strongly
      increases the chance of pathogen extinction.

PMID- 9650292
TI  - "Critical slowing down" in time-to-extinction: an example of critical phenomena
      in ecology.
AB  - We study a model for two competing species that explicitly accounts for effects
      due to discreteness, stochasticity and spatial extension of populations. The two
      species are equally preferred by the environment and do better when surrounded by
      others of the same species. We observe that the final outcome depends on the
      initial densities (uniformly distributed in space) of the two species. The
      observed phase transition is a continuous one and key macroscopic quantities like
      the correlation length of clusters and the time-to-extinction diverge at a
      critical point. Away from the critical point, the dynamics can be described by a
      mean-field approximation. Close to the critical point, however, there is a
      crossover to power-law behavior because of the gross mismatch between the largest
      and smallest scales in the system. We have developed a theory based on surface
      effects, which is in good agreement with the observed behavior. The course
      grained reaction-diffusion system obtained from the mean-field dynamics agrees
      well with the particle system.

PMID- 9650293
TI  - In vitro sulfotransferase activity of NoeE, a nodulation protein of Rhizobium sp.
      NGR234.
AB  - Soil bacteria of the genera Azorhizobium, Bradyrhizobium, and Rhizobium liberate
      morphogenetic lipochitin-oligosaccharides (Nod factors) into legume rhizospheres.
      Nod factors, which are synthesized by the products of rhizobial nodulation (nod)
      genes, vary in core length as well as in the number and type of substitutions. In
      Rhizobium sp. NGR234, the N-acylated pentamers of N-acetyl-D-glucosamine carry an
      O-methylfucose group on the reducing terminus that is substituted, on a mutually
      exclusive basis, with either an acetyl or a sulfuryl group. A sulfotransferase
      encoded by noeE is required for adjunction of activated sulfate donated by 3'
      phosphoadenosine 5'-phosphosulfate (PAPS). Here we show that when expressed in
      NGR234 cured of its symbiotic plasmid (= ANU265) or when purified as a fusion
      protein (MBP-NoeE), NoeE transfers sulfate from PAPS to fucosylated lipochitin
      oligosaccharides. Enzyme assays showed that sulfotransferase activity is
      dependent on the presence of an acyl group (stearic and vaccenic acids were
      tested) since no activity was detected when fucosylated oligochitins (oligomers
      of two to six N-acetyl-D-glucosamine units) were used as substrates. Thus, NoeE
      is unique in that it is the only characterized sulfotransferase that is specific
      for fucosylated Nod factors. It probably acts after NodA, which acylates the
      amino-sugar backbone.

PMID- 9650294
TI  - A virulence-associated, 6.4-kb, double-stranded RNA from Rhizoctonia solani is
      phylogenetically related to plant bromoviruses and electron transport enzymes.
AB  - We have recently shown that acquisition of a 6.4-kb, double-stranded (ds) RNA
      (M1) by hyphal anastomosis is associated with enhanced vigor and virulence,
      whereas its removal by hyphal tipping correlates with diminished virulence in the
      plant-pathogenic basidiomycete Rhizoctonia solani. The M1 dsRNA is not
      encapsidated by a typical nucleocapsid, has a circular and/or concatemeric form,
      and is associated with the mitochondrial and cytosolic fractions. M1 possesses
      six open reading frames (ORFs) the longest of which (ORF 2) is located on the (+)
      strand, and encodes a putative polypeptide consisting of 1,747 amino acids or
      199.4 kDa. This polypeptide has a significant amino acid sequence similarity,
      including six conserved helicase domains and an ATP/GTP binding motif, with the
      1A protein of broad bean mottle virus (BBMV) and other bromoviruses. ORF 5, which
      is located on the (-) strand of M1 and is complementary to a region of ORF 2,
      codes for a putative polypeptide that has a significant amino acid sequence
      similarity with the cytochrome c oxidase assembly factor. This complementarity
      provides direct evidence suggesting that the long-standing hypothesis of viruses
      evolving from cellular genes may be valid.

PMID- 9650295
TI  - Cell-to-cell movement of beet necrotic yellow vein virus: I. Heterologous
      complementation experiments provide evidence for specific interactions among the
      triple gene block proteins.
AB  - Cell-to-cell movement of beet necrotic yellow vein virus (BNYVV) requires three
      proteins encoded by a triple gene block (TGB) on viral RNA 2. A BNYVV RNA 3
      derived replicon was used to express movement proteins to functionally substitute
      for the BNYVV TGB proteins was tested by coinoculation of TGB-defective BNYVV
      with the various replicons to Chenopodium quinoa. Trans-heterocomplementation was
      successful with the movement protein (P30) of tobacco mosaic virus but not with
      the tubule-forming movement proteins of alfalfa mosaic virus and grapevine
      fanleaf virus. Trans-complementation of BNYVV movement was also observed when all
      three TGB proteins of the distantly related peanut clump virus were supplied
      together but not when they were substituted for their BNYVV counterparts one by
      one. When P30 was used to drive BNYVV movement in trans, accumulation of the
      first TGB protein of BNYVV was adversely affected by null mutations in the second
      and third TGB proteins. Taken together, these results suggest that highly
      specific interactions among cognate TGB proteins are important for their function
      and/or stability in planta.

PMID- 9650296
TI  - Differential involvement of indole-3-acetic acid biosynthetic pathways in
      pathogenicity and epiphytic fitness of Erwinia herbicola pv. gypsophilae.
AB  - Erwinia herbicola pv. gypsophilae (Ehg), which induces galls on Gypsophila
      paniculata, harbors two major pathways for indole-3-acetic acid (IAA) synthesis,
      the indole-3-acetamide (IAM) and indole-3-pyruvate (IPyA) routes, as well as
      cytokinin biosynthetic genes. Mutants were generated in which the various
      biosynthetic routes were disrupted separately or jointly in order to assess the
      contribution of IAA of various origins and cytokinins to pathogenicity and
      epiphytic fitness. Inactivation of the IAM pathway or cytokinin biosynthesis
      caused the largest reduction in gall size. Inactivation of the IPyA pathway
      caused a minor, nonsignificant decrease in pathogenicity. No further reduction in
      gall size was observed by the simultaneous inactivation of both IAA pathways only
      or in combination with that of cytokinin production. However, inactivation of the
      IPyA pathway caused a 14-fold reduction in the population of Ehg on bean plants.
      Inactivation of the IAM pathway or cytokinin production did not affect epiphytic
      fitness. While the apparent transcriptional activity of iaaM-inaZ fusion
      increased slightly in cells of Ehg on bean and gypsophila leaves, compared with
      that in culture, very high levels of induction were observed in cells injected
      into gypsophila stems. In contrast, moderate levels of induction of ipdC-inaZ in
      Ehg were observed on leaves of these plants and in gypsophila stems, when
      compared with that in culture. These results suggest that the IAM pathway is
      involved primarily in gall formation and support the main contribution of the
      IpyA pathway to the epiphytic fitness of this bacterial species.

PMID- 9650297
TI  - Induced resistance responses in maize.
AB  - Systemic acquired resistance (SAR) is a widely distributed plant defense system
      that confers broad-spectrum disease resistance and is accompanied by coordinate
      expression of the so-called SAR genes. This type of resistance and SAR gene
      expression can be mimicked with chemical inducers of resistance. Here, we report
      that chemical inducers of resistance are active in maize. Chemical induction
      increases resistance to downy mildew and activates expression of the maize PR-1
      and PR-5 genes. These genes are also coordinately activated by pathogen infection
      and function as indicators of the defense reaction. Specifically, after pathogen
      infection, the PR-1 and PR-5 genes are induced more rapidly and more strongly in
      an incompatible than in a compatible interaction. In addition, we show that
      monocot lesion mimic plants also express these defense-related genes and that
      they have increased levels of salicylic acid after lesions develop, similar to
      pathogeninfected maize plants. The existence of chemically inducible disease
      resistance and PR-1 and PR-5 gene expression in maize indicates that maize is
      similar to dicots in many aspects of induced resistance. This reinforces the
      notion of an ancient plant-inducible defense pathway against pathogen attack that
      is shared between monocots and dicots.

PMID- 9650298
TI  - Genetic characterization of RRS1, a recessive locus in Arabidopsis thaliana that
      confers resistance to the bacterial soilborne pathogen Ralstonia solanacearum.
AB  - The soilborne, vascular pathogen Ralstonia solanacearum, the causative agent of
      bacterial wilt, was shown to infect a range of Arabidopsis thaliana accessions.
      The pathogen was capable of infecting the Col-5 accession in an hrp-dependent
      manner, following root inoculation. Elevated bacterial population levels were
      found in leaves of Col-5, 4 to 5 days after root inoculation by the GMI1000
      strain. Bacteria were found predominantly in the xylem vessels and spread
      systematically throughout the plant. The Nd-1 accession of A. thaliana was
      resistant to the GMI1000 strain of R. solanacearum. Bacterial concentrations
      detected in leaves of Nd-1, inoculated with an hrp+ strain of R. solanacearum,
      were only slightly higher than those detected in the susceptible accession, Col
      5, following inoculation with a strain whose hrp gene cluster was deleted. Leaf
      inoculation of the GMI1000 strain on the resistant accession Nd-1 induced the
      formation of lesions in the older leaves of the rosette whereas the same strain
      of R. solanacearum provoked complete wilting of Col-5. Resistance to strain
      GMI1000 of R. solanacearum segregated as a simply inherited recessive trait in a
      genetic cross between Col-5 and Nd-1. F9 recombinant inbred lines generated
      between these two accessions were used to map a locus, RRS1, that was the major
      determinant of resistance between restriction fragment length polymorphism
      markers mi83 and mi61 on chromosome V. This region of the A. thaliana genome is
      known to contain many other pathogen recognition capabilities.

PMID- 9650299
TI  - Role of the Agrobacterium tumefaciens VirD2 protein in T-DNA transfer and
      integration.
AB  - VirD2 is one of the key Agrobacterium tumefaciens proteins involved in T-DNA
      processing and transfer. In addition to its endonuclease domain, VirD2 contains a
      bipartite C-terminal nuclear localization sequence (NLS) and a conserved region
      called omega that is important for virulence. Previous results from our
      laboratory indicated that the C-terminal, bipartite NLS and the omega region are
      not essential for nuclear uptake of T-DNA, and further suggested that the omega
      domain may be required for efficient integration of T-DNA into the plant genome.
      In this study, we took two approaches to investigate the importance of the omega
      domain in T-DNA integration. Using the first approach, we constructed a T-DNA
      binary vector containing a promoterless gusA-intron gene just inside the right T
      DNA border. The expression of beta-glucuronidase (GUS) activity in plant cells
      transformed by this T-DNA would indicate that the T-DNA integrated downstream of
      a plant promoter. Approximately 0.4% of the tobacco cell clusters infected by a
      wild-type A. tumefaciens strain harboring this vector stained blue with 5-bromo-4
      chloro-3-indolyl beta-D-glucuronic acid (X-gluc). However, using an omega-mutant
      A. tumefaciens strain harboring the same binary vector, we did not detect any
      blue staining. Using the second approach, we directly demonstrated that more T
      DNA is integrated into high-molecular-weight plant DNA after infection of
      Arabidopsis thaliana cells with a wild-type A. tumefaciens strain than with a
      strain containing a VirD2 omega deletion/substitution. Taken together, these data
      indicate that the VirD2 omega domain is important for efficient T-DNA
      integration. To determine whether the use of the T-DNA right border is altered in
      those few tumors generated by A. tumefaciens strains harboring the omega
      mutation, we analyzed DNA extracted from these tumors. Our data indicate that the
      right border was used to integrate the T-DNA in a similar manner regardless of
      whether the VirD2 protein encoded by the inciting A. tumefaciens was wild-type or
      contained an omega mutation. In addition, a mutant VirD2 protein lacking the
      omega domain was as least as active in cleaving a T-DNA border in vitro as was
      the wild-type protein. Finally, we investigated the role of various amino acids
      of the omega and bipartite NLS domains in the targeting of a GUS-VirD2 fusion
      protein to the nucleus of electroporated tobacco protoplasts. Deletion of the
      omega domain, or mutation of the 10-amino-acid region between the two components
      of the bipartite NLS, had little effect upon the nuclear targeting of the GUS
      VirD2 fusion protein. Mutation of both components of the NLS reduced, but did not
      eliminate, targeting of the fusion protein to the nucleus.

PMID- 9650300
TI  - Identification of an Arabidopsis thaliana mutation (vsm1) that restricts systemic
      movement of tobamoviruses.
AB  - Following inoculation, many plant viruses spread locally from cell to cell until
      they reach the vascular system, through which they then move to other parts of
      the plant, resulting in systemic infection. To isolate host genes involved in
      systemic transport of plant viruses, ethyl methanesulfonate-mutagenized
      Arabidopsis thaliana plants were screened for significant delays in the systemic
      movement of turnip vein clearing virus (TCVC). One such mutant, designated vsm1
      (virus systemic movement), was identified. Unlike the wild-type plants, vsm1 did
      not develop viral disease and did not allow the systemic spread of the virus. The
      local viral movement within the inoculated vsm1 leaves, however, was not
      affected. TVCV systemic movement within the vsm1 plants was likely blocked at the
      step of viral entry into the host plant vasculature from the infected leaf
      tissue. vsm1 plants also restricted the systemic movement of another tobamovirus
      but not of an unrelated carmovirus.

PMID- 9650301
TI  - Use of monoclonal antibodies to determine biomass of Cladosporium fulvum in
      infected tomato leaves.
AB  - A monoclonal antibody, OX-CH1, was raised against surface washings of
      Cladosporium herbarum. This antibody recognizes an epitope that is found in
      various fungi belonging to the genus Cladosporium, including C. fulvum, the
      causal agent of tomato leaf mold. The epitope is present at comparable levels in
      two different races of C. fulvum and in transgenic isolates derived from them.
      The epitope is heat-and protease-resistant but sensitive to oxidation with
      periodate and it is constitutively expressed in C. fulvum grown in pure culture
      and on the plant. C. fulvum can be detected in infected tissues at levels
      starting from around 1 mg fresh weight of fungus per g fresh weight of leaf
      tissue. Noninfected tomato leaves do not cross-react with OX-CH1. We have
      developed an enzyme-linked immunosorbent assay (ELISA) for fungal biomass in
      tomato leaves and compared it with the assay based on measurements of beta
      glucuronidase (GUS) activity in tissues infected with a transgenic isolate of C.
      fulvum race 4 carrying a uidA gene; the two assays give similar results.

PMID- 9650302
TI  - Quantification of ammonia in human breath by the selected ion flow tube
      analytical method using H30+ and 02+ precursor ions.
AB  - We show how our selected ion flow tube mass spectrometric technique for trace gas
      analysis can be used to determine the concentrations of ammonia in alveolar
      breath from single exhalations using both H30+ and 02+ precursor ions for
      chemical ionization. Thus, data are presented of the alveolar ammonia
      concentrations in the breath of six healthy volunteers following the ingestion of
      a liquid protein meal, which show that consistent values are obtained using these
      two precursor ions. Alveolar breath ammonia concentrations (which range from 200
      to 1750 ppb in these individuals) are compared with those obtained from bag
      samples of breath from the same individuals.

PMID- 9650303
TI  - Ion trap mass spectrometry for the characterization of N-methyl-1- (3,4-methylene
      dioxyphenyl)-2-butanamine and N-ethyl-3,4- methylenedioxyamphetamine, two widely
      distributed street drugs.
AB  - The potential of ion trap mass spectrometry has been evaluated for the
      characterization and distinction of two isomeric amphetamines drugs, namely N
      methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine and N-ethyl-3,4
      methylenedioxyamphetamine. Whereas the electron impact spectra of the two
      molecules lack specificity, collisional experiments on the ionic species at m/z
      72 allows unequivocal distinction between the two isomers. Analogous results are
      achieved by positive ion chemical ionization and collisional experiments on the
      protonated molecules. All the different approaches have been successfully applied
      to the gas chromatography/mass spectrometry analysis of a tablet of illicit drug.

PMID- 9650304
TI  - Further considerations on the use of matrix-assisted laser desorption/ionization
      mass spectrometry in the analysis of glycated globins.

PMID- 9650306
TI  - [Experimental microsurgery of the facial nerve: end-to-end suture versus
      approximated ends wrapped with masseter muscle aponeurosis].
AB  - As an alternative to end-to-end facial nerve microsurgery, we propose anastomosis
      of the sectioned nerve ends and wrapping with ipsilateral masseter fascia. This
      intervention was performed on the right facial nerve of 20 Wistar rats and
      compared with classical end-to-end anatomosis performed on the left nerve of the
      same rats. At the end of the experiment, histological studies were made of each
      nerve removed "en bloc" with the ipsilateral lip orbicular muscle. Five micra
      thick sections were stained using conventional and immunohistochemical methods.
      We analyzed truncal integrity, fibroblast proliferation, demyelination,
      lymphocyte proliferation, granulomatous reaction, and muscle degeneration in both
      types of anastomosis. The differences between the two types of anastomosis were
      statistically non-significant, and both interventions produced similar functional
      results. Small differences between the techniques might condition the use of one
      or the other in selected cases.

PMID- 9650305
TI  - [The effects of aging on the volume of human vestibular nuclei].
AB  - Elderly persons often have balance disorders, with dizziness that sometimes leads
      to falls. Changes in the peripheral vestibular system with age, with loss of the
      hair cells and neurons of Scarpa's nucleus, have been studied for years. However,
      the changes in the vestibular nuclear complex with age have not been examined. We
      studied paraffin-embedded brainstems from nine persons of different ages in order
      to analyze possible changes with age. No abnormalities were observed in the
      volume or length of the vestibular nuclei, except for a decrease in both
      dimensions in the superior vestibular nucleus (SNV). All the main vestibular
      nuclei showed an increase in lipofuscin content with age that seemed to be less
      marked in the SNV. The low lipofuscin concentration in the SNV could be related
      with the conservation of vestibular reflexes, the center of which seems to be the
      SVN, in elderly persons.

PMID- 9650307
TI  - [Comparative cephalometric study in patients with obstructive sleep apnea
      syndrome (OSAS), simple snorers and controls].
AB  - Lateral cranial teleradiography was carried out in 106 subjects, including obese
      and non-obese patients with obstructive sleep apnea syndrome (OSAS) and obese and
      non-obese healthy snorers and controls. In the OSAS patients alone, the hyoid
      bone occupied an abnormally low position, which pushed the tongue into a more
      vertical position. OSAS patients had the most voluminous soft tissues, followed
      by simple snorers and controls. Soft tissue volume generally was related with
      obesity. The pharyngeal airway space was widest in controls, intermediate in
      snores and narrowest in OSAS patients, except in the hypopharynx, where airway
      dimensions were similar in all the patients studied.

PMID- 9650308
TI  - [Surgical treatment of cholesteatoma: are wall-down techniques superior to wall
      up techniques? A 50-year-old controversy].
AB  - A retrospective study was made of the evolution of our policies in the surgical
      treatment of cholesteatoma between 1984 and 1993. An evaluation was made of 103
      patients operated by one of the authors [mean age 38 +/- 15 years; 60 (58%) men
      and 43 (42%) women]. The mean follow-up was 34 +/- 31 years. Binary logistical
      regression was used to analyze our patient series. Two factors that were
      associated statistically with the wall-down procedure were the degree of
      ossicular chain damage and the integrity of the posterior wall of the external
      auditory canal. The frequency of wall-down procedures has increased in our
      department.

PMID- 9650309
TI  - [study of acoustic trauma in hunters using otoacoustic emission recording].
AB  - Transitory otoacoustic emissions (TOAE) were analyzed in 48 ears of male hunters
      (age range: 30-45 years: mean age: 37 years) and in a population with normal
      hearing. All the ears had TOAE. The incidence of TOAE for the 1, 2, 3, 4, 5 and 6
      KHz frequential bands was significantly lower in hunters than in the normal
      subjects (p < 0.001). The mean amplitude of TOAE was significantly lower in
      hunters (9.2 dB SPL) than in the control group (16 dB SPL; p < 0.001). The
      amplitude of the TOAE for the frequencies 1, 2, 3, 4, 5 and 6 KHz was
      significantly lower in hunters than in controls (p < 0.001).

PMID- 9650310
TI  - [Diagnostic biopsy with paranasal sinus endoscopy].
AB  - Rigid endoscopy allows clear visualization of the nasal fossa and paranasal
      sinuses and permits biopsies to be obtained under direct vision from relatively
      inaccessible sites. In most cases the biopsy can be made using local anesthesia,
      but selected patients require general anesthesia. We report the results of 31
      patients who underwent biopsy with rigid nasal endoscopy under general
      anesthesia. Of the 31 patients, a diagnostic biopsy was achieved in 30 (96.7%).
      We define a diagnostic biopsy as one which yielded a histopathological diagnosis
      that did not change as a result of clinical findings, examinations or further
      biopsies performed during follow-up. We recommend the use of endoscopic nasal
      biopsy of nasal and paranasal neoplasms as an easy, safe and reliable technique.

PMID- 9650311
TI  - [Overexpression of p53 protein in epidermoid carcinoma of the pyriform sinus].
AB  - Mutation of the p53 protein may be the commonest genetic event in the development
      of malignant neoplasms in humans. We analyzed the immunohistological expression
      of p53 in tissue sections from 51 patients with squamous cell carcinoma of the
      pyriform sinus who were treated with surgery and postoperative radiotherapy.
      Overexpression of p53 was found in 37 (72.5%) tumors. No correlation was found
      between p53 overexpression and clinical and histopathological parameters.
      Recurrence and overall survival did not differ between p53-positive and p53
      negative cases.

PMID- 9650312
TI  - [Prevalence of voice disorders among educational professionals. Factors
      contributing to their appearance or their persistence].
AB  - A study was made of the prevalence of voice disorders and their risk factors in
      teaching professionals of Logrono, Spain. A prevalence and case-control study was
      made, including interviews, ENT examination, videostrobolaryngoscopy, perceptual
      evaluation of hoarseness, basic aerodynamic tests, the physical range of
      phonation, and a physical analysis of the acoustic signal. The prevalence of
      voice disorders among Logrono teachers was 17.7% (confidence interval: 12.1-25%).
      Nodular lesions (8.1%) were the most frequent pathology, followed by
      hyperfunctional dysphonia (4.1%), chronic laryngitis (2.7%), polyps (1.4%),
      hypofunctional dysphonia (0.7%), and submucous suffusion (0.7%). Voice disorders
      were more prevalent in women (19.3%) than in men (15.6%), and among teachers of
      the lowest grades: 36.4% in nursery schools, 25% in elementary school, and 20.8%
      in junior school. The width and depth of classrooms, larger number of students,
      longer classroom hours, and noise level were related with the frequency of voice
      disorders.

PMID- 9650313
TI  - [Prognostic value of morphometry and nuclear stereology in laryngeal epidermoid
      carcinoma].
AB  - BACKGROUND AND METHODS: A series of 70 consecutive patients with laryngeal
      carcinoma treated by induction chemotherapy is reported. The prediction of the
      response to induction chemotherapy was evaluated by nuclear morphometric and
      stereological analysis of the tumor cells. RESULTS: Statistically significant
      differences were found in the nuclear form factor (FF, p < 0.021) and nuclear
      contour index (NCI, p < 0.017) between the groups of patients with a complete
      response (CR), partial response (PR) or no response (NR) to induction
      chemotherapy. Comparison of the groups of patients with partial response or
      complete response to IC with the group with no response yielded statistically
      significant differences in the nuclear form factor (FF, p < 0.002), nuclear
      contour index (NCI, p < 0.0032) and nuclear orientation angle (NOA, p < 0.036).
      CONCLUSION: Nuclear morphometric analysis of the tumor cells was a useful tool
      for predicting response to induction chemotherapy in a significant number of the
      patients with laryngeal tumors in our series.

PMID- 9650314
TI  - [Laryngeal granular cell tumor].
AB  - Granular cell tumors are rare benign neoplasms. Their usual location is in the
      head and neck, with the larynx being the most frequent ENT site. Three cases of
      granular cell tumor of the larynx are reported and their characteristics are
      reviewed.

PMID- 9650315
TI  - [Benign paroxysmal vertigo in childhood].
AB  - Benign paroxysmal vertigo of childhood is a clinical disorder that usually begins
      at age 4. The child's otoneurological examination is normal in the intercrisis
      and the brief episodes of true vertigo are typical. In this paper we describe six
      new cases that had a follow-up of at least one year after diagnosis. Only a few
      of the patients had demonstrated vasomotor migraine, but all the children had a
      family history of migraine, which supports the hypothesis that this disorder is a
      migraine equivalent. The pathogenesis may be related with a transitory vascular
      disturbance that produces ischemia of the vestibular nuclei and pathways, as
      occurs in other vascular territories during typical migraine. One longer-than
      usual episode is reported. Otherwise, the evolution of this condition is
      favorable.

PMID- 9650316
TI  - [Invasive giant prolactinoma].
AB  - Large prolactin-secreting tumors are rare and their endocrinological and surgical
      management may be complex. We report the case of a patient with a prolonged
      history of unilateral tinnitus and sensation of a stopped-up ear who had a very
      large, invasive and aggressive tumor of the sphenoidal region with bone
      destruction, invasion of structures in every direction from the sellar region and
      extracranial extension to the ethmoid and nasopharynx. Serum prolactin level at
      the time of diagnosis was 16,860 ng/ml (normal: 3-17 ng/ml). Medical treatment
      with bromocriptine reduced the prolactin level to 31 ng/ml and reduced the size
      of the tumor, although less than expected. The literature is reviewed and the
      rarity of such large, invasive prolactinomas is highlighted, as well as the
      absence of symptoms and signs suggesting the presence of such a large tumor of
      the skull base.

PMID- 9650317
TI  - [Malignant pleomorphic adenoma of the palate].
AB  - Pleomorphic adenoma or mixed tumor is the most common benign neoplasm of the
      minor salivary glands. These tumors rarely have malignant features. Three
      varieties are differentiated by histological features and tumor behavior. Whether
      malignant tumors develop on benign adenomas or are malignant from onset is still
      not known. A malignant mixed tumor of the minor salivary glands of the palate is
      reported. The difficulty of histological diagnosis, in spite of
      immunohistochemical techniques, is emphasized and the surgical treatment is
      described.

PMID- 9650318
TI  - [Ethmoid metastasis of primary breast tumor].
AB  - Metastatic tumors to the paranasal sinuses are uncommon. Symptoms and imaging
      studies are non-specific and usually similar to primary neoplasms in this region.
      Histological study of the neoplastic tissue is essential in order to ascertain
      its origin. A case of breast adenocarcinoma that metastasized to the ethmoid
      sinus is reported and the literature is reviewed.

PMID- 9650319
TI  - [Cavernous hemangioma of the maxillary sinus].
AB  - A 67-year-old man had an intraosseous giant cavernous hemangioma in maxillary
      sinus. We describe the MRI features of the case and note the potential risk of
      performing office biopsies on such lesions. Our patient did not have profuse
      hemorrhage and preventive measures were taken.

PMID- 9650320
TI  - [Postsurgical hyponatremia].
AB  - Hyponatremia is a relatively common postoperative complication which sometimes
      has dramatic consequences. A case of severe hyponatremia is reported. Although
      unrelated with the surgical technique, this complication is potentially life
      threatening.

PMID- 9650321
TI  - [Laparoscopic feeding gastrostomy: an alternative to the nasogastric tube].
AB  - Dysphagia is common in head and neck cancer and feeding becomes difficult.
      Nasogastric tubes cannot by placed in some patients and are poorly tolerated in
      others. However, endoscopic laparotomy techniques have advanced to a point in
      which they allow feeding gastrostomies to be used, which are non-aggressive, well
      tolerated and a satisfactory alternative for patients with contraindications for
      upper endoscopy.

PMID- 9650322
TI  - [Facial paralysis after non-otologic surgery under general anesthesia].
AB  - Peripheral facial palsy is rare after non-otological surgery under general
      anesthesia. The condition generally is attributed to damage produced by
      endotracheal intubation maneuvers in patients with anatomic variants of the
      facial nerve. We report three cases of facial palsy which occurred after
      abdominal surgery. In every case, nitrous oxide gas was used in anesthesia. One
      patient had intubation via tracheostomy; all the patients had endocranial facial
      symptoms and a history of previous surgery. The diversity of these factors
      suggests that other mechanisms of production aside from damage produced by
      endotracheal intubation should be considered. The use of nitrous oxide increases
      middle ear pressure and could produce focal nerve compression. This does not
      invalidate earlier hypotheses, but does clarify pathophysiological concepts of
      this condition.

PMID- 9650323
TI  - Are case reports obsolete?

PMID- 9650324
TI  - Effects of colchicine and colchiceine in a biochemical model of liver injury and
      fibrosis.
AB  - BACKGROUND: The accumulation of collagen is a salient feature of chronic liver
      injury. The objective of this study was to investigate and compare the
      therapeutic effectiveness of colchicine and one of its metabolites, colchiceine,
      to protect rats from developing liver injury and fibrosis. METHODS: To accomplish
      this, the authors used a procedure developed by others to produce liver injury
      and fibrosis by chronic administration of CCl4 in rats. The effect of both
      compounds on collagen metabolism and liver injury was analyzed. RESULTS: Although
      both compounds prevented increase in collagen synthesis, animals treated with
      colchicine did not show a reduction in collagen content compared with animals
      treated with CCl4. On the other hand, the animals treated with colchiceine along
      with CCl4 showed a 50% reduction in hepatic collagen content as well as an
      improvement in histological architecture. Both compounds, colchicine and
      colchiceine, increased the intracellular degradation of collagen in addition to
      increasing collagenase activity as compared to non-treated rats. However,
      collagenase activity was lower in animals treated with colchicine and colchiceine
      than in the fibrotic livers treated with CCl4. The changes in collagen metabolism
      correlated with changes in parameters of liver injury. CONCLUSIONS: In
      conclusion, the compound colchiceine may be recommended in the treatment of
      chronic liver diseases rather than its precursor, colchicine, due to the fact
      that it showed a lower accumulation of collagen content and has a better anti
      fibrogenic effect than does colchicine.

PMID- 9650325
TI  - Progesterone: protective effects on the cat hippocampal neuronal damage due to
      acute global cerebral ischemia.
AB  - BACKGROUND: Barbiturates, benzodiazepines, and synthetic steroids having
      anesthetic properties, by enhancing the inhibitory GABAergic neurotransmission to
      the neuronal circuits of cerebral structures vulnerable to ischemia, reduce the
      damage induced by this condition. Some endogenous steroids resulting from
      progesterone (P4) biotransformation in the brain exert GABAergic effects, thus
      inhibiting neuronal excitability. Hence, P4 administration both before and after
      an experimentally induced ischemic episode may prevent or decrease the ischemic
      cerebral damage. METHODS: Ovariectomized adult cats were treated s.c. with either
      P4 (10 mg/kg/day) or corn oil during 7 days before and 7 days after being
      subjected to a period of acute global cerebral ischemia by 15 min of
      cardiorespiratory arrest followed by 4 min of reanimation. After 14 days of
      survival, animals were sacrificed and the brains perfused in situ and formalin
      fixed for histological examination. RESULTS: Acute global cerebral ischemia
      resulted in a severe loss of neurons (54-85%), mainly in CA1 and CA2 subfields of
      oil-treated cats. Progesterone significantly reduced the neuronal loss in those
      areas (21-49%). CONCLUSIONS: Overall results suggest that progesterone exerts
      protective effects against the neuronal cerebral damage induced by acute global
      cerebral ischemia.

PMID- 9650326
TI  - The hindlimb hyperextension associated to the urogenital response in newborn
      underfed rats.
AB  - BACKGROUND: The aim of the study was to investigate how neonatal undernutrition
      interacts with mother-infant relationships to interfere with the expression of
      the urogenital response in the newborn. METHODS: The hyperextensive reflex
      components associated to the urogenital response (HUR) were measured between
      postnatal days 1-21, in control and neonatally undernourished rats with or
      without fullness of the bladder. RESULTS: In Experiment 1, both male and female
      underfed rats with different degrees of bladder fullness exhibited an increment
      in HUR latency and vertical hindlimb displacement, reduced transversal separation
      and prolonged performance of hindlimb relaxation. Experiment 2 was performed in
      rats after urine elicitation provoked only reduced hindlimb transversal
      separation in males, and prolonged latency to HUR in females. DISCUSSION: These
      findings may be related to the vulnerability to neonatal undernutrition of the
      maturational processes which take place in the spinal cord, the condition of the
      bladder, and hindleg muscle maturation during this period of life. CONCLUSIONS:
      Data suggest that neonatal undernutrition may play a role in mother-infant
      interaction by interfering with HUR responses to maternal anogenital licking of
      the pups.

PMID- 9650327
TI  - Biotypes and serotypes of Haemophilus influenzae of clinical isolates from
      Mexican children.
AB  - BACKGROUND: Infectious diseases caused by H. influenzae type b are considered
      preventable through vaccination with Hib conjugate vaccines. Some countries which
      follow Hib vaccination programs are close to eradication of the disease. In
      Mexico in particular, little epidemiological information is available. METHODS:
      In this study, 90 clinical strains of H. influenzae were obtained from Mexican
      children who were treated in four pediatric hospitals in Puebla City, and were
      diagnosed with invasive or localized infectious diseases. The strains were
      identified by standard bacteriological methods. Biotyping was done by Kilian
      criteria and serotyping by coagglutination. RESULTS: H. influenzae infections
      were found in children younger than 5 years of age, and 68.8% of the children
      were younger than 24 months. Sixty percent of the isolates belonged to serotype
      b, 31.1% were nontypeable, and 7.7% were considered non-type b. Serotype b was
      the most frequent isolate associated with invasive infectious diseases; however,
      nontypeable strains were isolated more frequently from children with otitis,
      sinusitis, conjunctivitis, and bronchial secretion. Non-type b serotypes were
      isolated from invasive and non-invasive infections in few cases. Biotypes I and
      IV were the most frequent isolates of H. influenzae. CONCLUSIONS: This study
      emphasizes the urgent need for an Hib-conjugated vaccine to achieve immunization
      in a pediatric population.

PMID- 9650328
TI  - Lowering glycemic index of food by acarbose and Plantago psyllium mucilage.
AB  - BACKGROUND: A study was designed to evaluate the effect of acarbose and Plantago
      psyllium mucilage on glycemic index (GI) of bread. METHODS: Twelve patients with
      non-insulin-dependent diabetes mellitus (NIDDM) and ten healthy volunteers were
      studied. Three meal tests with an intake of 90 g of white bread (50 g of
      carbohydrates) were performed on each subject. In one test, 200 mg of acarbose
      was given, while 15 g of P. psyllium mucilage was given in another test, and only
      bread was ingested in the control test. Serum glucose and insulin concentrations
      were measured every 30 min from 0-180 min. Net area under curve (AUC)
      concentrations of glucose and insulin, GI and insulinic index were calculated.
      RESULTS: In NIDDM patients, AUC-glucose in the test with acarbose (1.9 +/- 0.7
      mmol/L) and with P. psyllium (4.3 +/- 1.2 mmol/L) were significantly lower than
      in the control test (7.4 +/- 1.5 mmol/L) (p < 0.01). GI of bread plus acarbose
      was 26 +/- 13, and of bread plus P. psyllium, 59 +/- 10 (p < 0.05). AUC-insulin
      and insulinic index behave similarly. In healthy individuals, AUC-glucose and GI
      did not significantly change with the treatments; however, insulinic index with
      acarbose was 17 +/- 16, and with P. psyllium was 68 +/- 15 (p < 0.05). Acarbose
      or P. psyllium decreased GI of bread in NIDDM patients and diminished insulinic
      index in NIDDM and in healthy subjects. CONCLUSIONS: Adding acarbose or P.
      psyllium to meals may reduce glycemic index of carbohydrate foods and may help
      diabetic control.

PMID- 9650329
TI  - Recognition of Streptococcus pyogenes and skin autoantigens in guttate psoriasis.
AB  - BACKGROUND: Guttate psoriasis is associated with infections by Streptococcus
      pyogenes and cross-reactions between skin and streptococcal antigens have been
      reported, suggesting an autoimmune component in the disease. METHODS: In this
      work, the authors looked for antibodies against S. pyogenes M-5 antigens by
      immunoblot in 52 sera of psoriasis patients and in 52 sera of normal individuals.
      Histological and immunohistochemical analysis in skin biopsies from lesions of
      another group of 16 clinically diagnosed guttate psoriasis patients and four
      healthy controls were also carried out. RESULTS: All guttate psoriasis patients
      studied (11) had IgG antibodies that intensively recognized three different
      proteins of 70, 60 and 14 kDa, as compared to sera from patients with other forms
      of psoriasis or from healthy controls. The diagnosis of psoriasis was confirmed
      in 14 of the patients by hematoxylineosin staining. Of the other two patients,
      one was diagnosed as parapsoriasis and the other as liquen. By indirect
      immunofluorescence (IFI), all 14 psoriatic patients had autoantibodies against
      their own lesional skin that did not recognize normal skin from control subjects
      or from the two non-psoriatic patients. The parapsoriatic and the liquen patients
      did not have autoantibodies. A rabbit immune serum against S. pyogenes antigens
      reacted with lesional skin from the 14 guttate psoriatic patients, but not with
      normal skin from controls or with lesional skin from the 2 non-psoriatic
      patients. CONCLUSIONS: The recognition by immunoblot of streptococcal antigens by
      serum of guttate psoriasis patients, the presence of autoantibodies against their
      own skin, and recognition of the same skin antigens by anti-streptococcal rabbit
      antibodies confirm the participation of the immune system and of streptococcal
      infections in guttate psoriasis.

PMID- 9650330
TI  - Studies on nap sleep in young students. Relationships between polygraphic data
      and the occurrence of dreams in replacing naps.
AB  - BACKGROUND: Afternoon nap sleep was studied in 32 young male medical students who
      take customary naps to replace loss in nocturnal sleep. METHODS: From 16
      subjects, a group called dreamers was formed, and the other 16 individuals were
      grouped as non-dreamers. Polygraphic recordings lasting 30 min were done at a
      fixed time in the afternoon, and the relationship between these data and the
      occurrence of dreams was investigated. RESULTS: We found that this replacing of
      nap sleep can adopt different sequences and relative durations of its phases, and
      can also show individual variations that have a systematic relationship with the
      occurrence of dreams. It was observed that dreaming was closely related to the
      appearance, during the first 10 minutes of the nap, of Stage I with Slow Eye
      Movements, interrupted by Sleep Onset REM Periods (SOREMPs) and, to a lesser
      degree, to phases IV and III of slow sleep. CONCLUSIONS: According to these
      findings, the existence of dreamers and non-dreamers depends upon the
      relationship between an internal sleep-waking rhythm, and an external rhythm
      imposed by the daytime resting-activity schedule on the habit of dreaming, and,
      to a certain extent, on the mental phenomena occurring between the generation of
      dreams and the moment of awakening.

PMID- 9650331
TI  - Prognostic significance of cutaneous depigmentation in Mexican patients with
      malignant melanoma.
AB  - BACKGROUND: The clinical significance of cutaneous depigmentary phenomena in
      patients with malignant melanoma is not clear. There are two varieties: 1)
      vitiligo (VIT), and 2) leukoderma acquisitum centrifugum (LAC). METHODS: In order
      to evaluate the outcome of our patients with malignant melanoma and skin
      depigmentation (VIT or LAC), the patients in this study with this association
      were retrospectively reviewed and compared with the total melanoma patients at
      the Oncology Hospital and the XXI Century National Medical Center of the Mexican
      Social Security Institute in Mexico City. RESULTS: Nine cases were found from
      1985-1995. There were eight women and one man, their mean age was 63 years. Six
      melanomas were located in the foot, one in the leg, one in the anus and one in
      the neck. All were Clark's levels III, IV or V, and their mean tumor thickness
      was 5.7 mm. Four out of nine patients had regional lymph node metastasis. Six
      melanomas were associated with VIT and three with LAC. Three patients developed
      the depigmentation after chemo- or chemoimmunotherapy. All nine patients are
      alive (100%) with a mean follow-up of 55 months (9-141), eight out of nine have
      no evidence of tumor. CONCLUSIONS: From these data it may be concluded that the
      study patients with malignant melanoma and VIT or LAC have a higher-than-expected
      survival according to their prognostic factors. Therefore, the presence of the
      depigmentation phenomena must be looked for intentionally.

PMID- 9650332
TI  - Immediate results of the Inoue mitral valvotomy in patients with previous
      surgical mitral commissurotomy. Preliminary report.
AB  - BACKGROUND: The objective of this study is to evaluate the immediate result of
      the percutaneous mitral valvotomy in patients with previous surgical mitral
      commissurotomy, compared with patients considered ideal for the performance of
      the procedure. METHODS: The authors of this paper compared the immediate results
      of the percutaneous mitral valvotomy (PMV) performed on two groups of patients.
      Group I included 20 patients who were good candidates for PMV, with an
      echocardiographic score of < or = 8, without evidence of left atrial thrombus,
      and with no recent embolic event. Group II included seven patients with previous
      mitral commissurotomy (MC). RESULTS: According to the Wilcoxon non-parametric t
      test analysis, the hemodynamic variables changed significantly in the patients of
      group I: the mitral area increased from 1.21 +/- 0.41 to 2.62 +/- 0.75 cm2 (P = <
      0.001); the mean left atrial pressure decreased from 17.2 +/- 7.2 mmHg to 9.2 +/-
      4.5 mmHg (P = < 0.001), and the pressure transmitral gradient decreased 12.4 +/-
      6.8 to 3.3 +/- 1.26 mmHg (P = < 0.001). No statistically significant difference
      in the hemodynamic changes of the patients of group II after the PMV was found:
      the mitral area increased from 1.2 +/- 0.2353 to 1.96 +/- 0.57 cm2; the mean left
      atrial pressure decreased from 17.42 +/- 10.35 to 12.42 +/- 7.3 mmHg, and the
      pressure mitral gradient decreased from 11.47 +/- 6.5 to 5.7 +/- 4.8 mmHg. The
      mitral area determined by echocardiographic procedure showed the same tendency in
      patients with previous MC. CONCLUSIONS: In spite of this tendency, during the
      follow-up after PMV the NYHA functional class decreased from II-IV to I in the
      patients with previous MC. Because a second surgical MC results in higher
      mortality, PMV is indicated in patients with previous MC, delaying or avoiding a
      second MC or valve replacement.

PMID- 9650333
TI  - Maternal mortality regionalization and trend in Mexico (1937-1995)
AB  - BACKGROUND: The objectives were to establish regions by level of maternal
      mortality in order to evaluate its trend from 1937-1995 and to analyze
      characteristics of cases which occurred from 1990-1995. METHODS: Regionalization
      of the country by maternal mortality level was carried out using Poisson
      regression. Level and mortality trends were analyzed globally and compared by
      regions using Poisson and linear regression. Characteristics of cases were
      analyzed from 1990-1995 using proportions and X2 test. RESULTS: Four well
      differentiated and independent regions were established. Low and medium maternal
      mortality rate regions were found in northern and northwestern Mexico. High and
      very high maternal mortality regions were found in the South and the Southeast of
      the country. Even when maternal mortality had descended, the speed of the descent
      has decreased and in the last few years, maternal mortality has increased. The
      quality of health care is a challenge for regions with low mortality rates, while
      the problem of accessibility is present in those with very high mortality rates.
      CONCLUSION: The employment of this regionalization approach in maternal mortality
      analysis would be useful to determine specific problems for each region. The
      establishment of programs according to this analysis could contribute to decrease
      in maternal mortality cases in Mexico.

PMID- 9650334
TI  - Risk factors of stroke at high and low altitude areas in Saudi Arabia.
AB  - BACKGROUND: The epidemiology of stroke at different geographical locations in the
      Kingdom of Saudi Arabia has not been adequately investigated. METHODS: In this
      study, clinical types and risk factors of stroke were compared among patients at
      low-altitude (Riyadh, 620 m) and high-altitude (Al Baha > 2000 m) areas using a
      case-control study design. One-hundred ninety recently diagnosed cases (109 from
      Riyadh and 81 from Al Baha) were verified and subjects were interviewed. An equal
      number of age- and sex-matched controls from the corresponding areas were also
      interviewed using a specific standard questionnaire. RESULTS: The frequency of
      thrombotic stroke at high altitude was 93.4% as compared to 79.3% at low altitude
      (P < 0.05). The odds ratios (OR) for the different risk factors at high and low
      altitudes, respectively, were: hypertension 4.4 and 2.1; diabetes mellitus: 2.7
      and 1.9; ischemic heart disease (IHD): 2.4 and 1.9; atrial fibrillation: 3.9 and
      3.3, and smoking: 2.3 and 2.5. The mean hematocrit values were 45.3% at high
      altitude and 41.0% for low altitude patients (P < 0.001) and its association with
      stroke at high altitude remained significant even after adjusting for age, gender
      and occupation. CONCLUSIONS: The study's finding of an increased frequency of
      thrombotic stroke at high altitude was explained by increased hematocrit which
      might have caused this in conjunction with other factors such as hypertension and
      IHD. Larger studies are recommended for better clarification of interaction
      between high altitude and other established risk factors not included in this
      study, such as sickle cell anemia and congenital heart diseases in young
      patients.

PMID- 9650335
TI  - Risk factors for amputation in diabetic patients: a case-control study.
AB  - BACKGROUND: The objective was to quantify risk factors for lower extremity
      amputation in patients with diabetes mellitus in an attempt to prevent
      amputation. METHODS: This investigation was conducted as a case control study
      among diabetic males from 30-90 years of age with an average clinical duration of
      diabetes of 10 years: included were 80 cases which required a supracondyle
      amputation associated with diabetes mellitus, and 240 controls without injuries
      in the lower extremities. Measurements included the following: socioeconomic
      level, psychosocial risk factors, neuropathics, peripheral vascular factors, high
      blood pressure, smoking; environmental factors, health care, self care, and
      nutritional and metabolic factors in patients with diabetes mellitus before
      surgery. Statistically significant risk factors identified from analyses were:
      absence of lower leg vibratory perception (odds ratio = 14.9, 95% CI: 8.2-27.9);
      peripheral vascular disease (OR = 8.9, 95% CI: 5.3-15.9); high blood cholesterol
      > 450 mg (OR = 3.8, 95% CI: 2.9-8.6); low blood albumin < 3.5 g (OR = 7.9, 95%
      CI: 4.8-14.9); hyperurea blood nitrogen > 3.5 mg (OR = 3.1, 95% CI: 1.7-4.9);
      obesity (OR = 4.2, 95% CI: 1.51-9.8); time of evolution of diabetes mellitus > 10
      years (OR = 3.47, 95% CI: 1.40-8.56); cracks in feet (OR = 3.45, 95% CI: 1.33
      8.82); feet soaked in water (OR = 1.8, 95% CI: 1.07-2.93); ingrown toenails (OR =
      2.0, 95% CI: 0.6-5.3), and lack of outpatient diabetes education (OR = 3.2, 95%
      CI: 1.5-6.7). CONCLUSIONS: Different risk factors for lower extremity amputation
      in diabetes mellitus patients were quantified, identifying certain aspects of
      preventive impact (patient education, glycemic control, careful daily foot
      hygiene, and appropriate footwear) which may be applicable in environmental
      factors and which have the possibility of success in lowering the rate of risk
      for lower extremity amputation.

PMID- 9650336
TI  - Localization of intranuclear RNA by electron microscopy in situ hybridization
      using a genomic DNA probe.
AB  - BACKGROUND: The presence of RNA in the cell nucleus is well known. However, a
      high resolution in situ hybridization evidence for the presence of RNA in some
      nuclear particles is still lacking. The aim of this work is to localize RNA in
      subnuclear particles using a novel ultrastructural in situ hybridization
      procedure. In this study, biotinylated genomic mouse DNA as a probe to localize
      total RNA in the nuclei of mouse hepatocytes was used. METHODS: The procedure is
      based on paraformaldehyde fixation and embedding in lowicryl resin. Thin sections
      are mounted in formvar-coated gold grids. Hybridization is performed on non
      denatured thin sections. DNA-RNA hybrids are detected with streptavidin-10 nm
      gold particles complex. By controlling the time of nick-translation during
      incorporation of biotin into the probe, labeling in the fibrillar portions of the
      nucleoplasm is obtained. More digested probes generate more labeling in the
      granular components. Nucleoli were similarly labeled. RESULTS: As expected, no
      label was observed in the compact chromatin clumps. These results indicate that
      granular components as perichromatin granules in the nucleus contain more
      processed RNA than fibrillar portions. As a comparison, viral DNA sequences on
      denatured RNase-treated thin sections of adenovirus-2 (Ad-2)-infected human cells
      were detected. As previously reported, at late stages DNA was observed in the
      viral particles and surrounding nucleoplasm, where Ad-2 DNA is synthesized.
      CONCLUSIONS: The present procedure allows the study of intranuclear RNA
      distribution and will be useful for the analysis of RNA processing in several
      types of cells.

PMID- 9650337
TI  - Antimicrobial compounds detected in Bocconia arborea extracts by a direct
      bioautographic method.
AB  - BACKGROUND: Among the numerous in vitro methods for studying the antimicrobial
      activity of plant drugs, bioautography has found widespread applications,
      especially for the detection of new compounds in complex plant extracts. METHODS:
      This paper describes the results obtained during the application of the
      bioautographic method to detect antimicrobial compounds in a chloroformic extract
      of leaves and stems of Bocconia arborea, a plant used profusely in traditional
      medicine for the treatment of diverse infectious diseases. RESULTS AND
      CONCLUSIONS: The methods allows for the detection of spots of growth inhibition
      of cultures directly in the extract thin layer chromatographic plate previously
      dispersed with a broth culture containing the microorganisms. The procedure also
      allowed for the detection of the presence of several products in the B. arborea
      extract with considerable activity against five different microorganisms.
      Additionally, the method allowed the determination that the antimicrobial
      activity is due to compounds of probable alkaloid origin.

PMID- 9650338
TI  - Chagas disease. First congenital case report.
AB  - This is the first report of a congenitally transmitted case of Chagas disease
      occurring in Mexico, in a febrile premature newborn girl with low birth weight,
      hepatosplenomegaly and pneumonitis. Trypanosoma cruzi blood infection was
      detected using both direct smears and concentrated blood preparations. The
      patient's mother had a positive serological reaction by two techniques for anti
      T. Cruzi antibodies. Two years after anti-chagastic treatment, the child has had
      a normal evolution, her serology is negative, and no abnormalities have been
      detected by electrocardiography.

PMID- 9650339
TI  - [650th anniversary of the founding of Charles University. Six- and-one-half
      centuries of medical education in Prague].

PMID- 9650340
TI  - [Endocrinology 1996-1997].
AB  - Post-traumatic stress-induced disorders are still the focus of interest and most
      recently discussions are under way whether stress-induced cortisol excess leads
      to atrophy of the brain. In investigation on carcinogenesis the first reports
      were published on the use of antisense-oligonucleotides during inhibition of the
      development of tumours by a humoral mechanism and on the gene-based
      neuroendocrine differentiation of the lungs, perhaps associated with the basis
      for the development of small cell carcinoma. The oncogenic action of superoxides
      has also humoral mediators. Interest in nitrogen oxide is focused on two areas:
      inflammations and hypertension. Intraluminal NO concentrations increase in asthma
      2-10x, in cystitis 30-100x, in Crohn's disease 20-200x. Humoral mechanisms in
      asthma offer new drugs--inhibitors of the development or action of leucotrienes.
      The basal NO production is reduced in "essential" hypertension but it is not
      known whether it is the cause or consequence. IGF-I increases the formation of NO
      in the vascular wall and thus perhaps reduces vascular contractility. As far as
      IGF is concerned, it is obvious that if recombinant preparations will be
      available, they will be tested in amyotrophic lateral sclerosis, myotonic
      dystrophy, multiple sclerosis, catabolic conditions, osteoporosis, in renal
      failure and to promote wound healing. STH may also prove useful in cardiac
      failure, in particular in cardiac cachexia. That TRH has receptors in the gut is
      not surprising, it acts, however, even there via TSH. Thrombopoietin is being
      tested in clinical trials. Neocytolysis is a new phenomenon: when erythropoietin
      secretion declines new erythrocytes disappear and only old ones remain in the
      blood stream. Alpha-adducin is a renal tubular protein, regulating the sodium
      balance.

PMID- 9650341
TI  - [Fluorine in the prevention of dental caries].
AB  - Classical epidemiological trials which were implemented in localities with a
      natural fluoride concentration in drinking water provided evidence that a
      concentration of 1 mg per 1 litre of water ensures on optimal preventive effect
      as regards dental caries and has no adverse effects on the health status of the
      population. In 1945 fluoride supplementation of drinking water was started in the
      USA, then in Canada, Chile, Brazil, New Zealand. Based on experience of overseas
      countries, this type of prevention of dental caries was started also in European
      countries. In the Czech Republic fluoridation of drinking water introduced in
      1958 in Tabor and in the course of 25 years it was introduced in 567 localities.
      Control examinations in these localities provided evidence of a reduction of
      caries experience on average by 40-50% in deciduous as well as permanent
      dentition. Despite clearly proved advantages, fluoride prevention has adversaries
      who are motivated emotionally or politically and their views are not consistent
      with health authorities. In the Czech Republic fluoridation of drinking water was
      discontinued in 1988 in Prague and from 1993 in the whole Republic
      Discontinuation of fluoridation led to an alarming situation in particular in
      preschool children where caries experience and the percentage of children with
      intact teeth reached the level recorded twenty years ago.

PMID- 9650342
TI  - [Analysis of mortality trends in the West Bohemian Region in comparison with the
      entire Czech Republic 1988-1995].
AB  - BACKGROUND: Unfavourable trends in Czech republic (CR) started in the sixties and
      peaked in the late eighties i.e. in years when a dramatic mortality fall was
      observed in most western european countries. So, CR belonged among those Eastern
      European countries in that total and cardiovascular mortality showed increasing
      and alarming trends. West Bohemia Region (WB) was characterised by the
      concentration of heavy industry and high environmental pollution. Because of its
      geographical position on the western frontier, it was generally restricted in
      capital investment in the past. We wondered whether these phenomenon were
      reflected in higher mortality rates than in the rest of CR and which changes
      occurred after the year 1989. METHODS AND RESULTS: We compared the age
      standardized mortality data from 1988, 91, 93 and 95 in CR and WB for total
      mortality, cardiovascular mortality, coronary heart disease, strokes,
      malignancies and respiratory diseases. Data were age-adjusted for "World
      Population Standards" and rates were given for 100,000 inhabitants. In the whole
      CR a significant decrease of total, cardiovascular and cancer mortality was
      observed from 1988 to 1995. In WB these trends were similar, however in
      comparison to the whole CR the mortality rates remained in each respective period
      higher for total, cancer (mainly lung cancer) mortality and for non specific
      respiratory disease. In contrast, the coronary mortality rates in CR and WB were
      similar, however in WB after a temporary decrease in 1993 a significant increase
      in 1995 was observed. On the other hand the stroke mortality rates which were
      until 1993 in WB higher, significantly decreased in 1995 below the rates for CR.
      The cause of higher mortality rates in WB are far from being clear. To elucidate
      this observation epidemiologic studies of environmental pollution, life style of
      the population and socioeconomic factors are necessary, even as a further
      monitoring of regional mortality rates and trends.

PMID- 9650343
TI  - [Surgical treatment of bronchogenic carcinoma. Long-term results in 496 surgical
      patients].
AB  - BACKGROUND: The operability of lung cancer and the period of survival after
      resection of the lungs in our country does not yet attain the standard recorded
      in some advanced countries. The objective of the present work is to analyze
      factors which influence the survival period after resection therapy of lung
      cancer. METHODS AND RESULTS: In 1985-90 in our department 496 patients were
      operated on account of lung cancer. This number comprised 31 patients subjected
      to explorative thoracototomy and three patients with pulmonary resection on
      account of a stage IIIb (pTNM) tumour who were excluded from the statistical
      analysis. The retrospective study proper analyzes the results of 462 patients
      (403 men and 59 women) operated in stages I, II and IIIa. Their mean age was 57
      years (range 30-74 years, SD 7.5 years). The most frequent histological type was
      epidermoid carcinoma (68.8%), adenocarcinoma 18.2%, small-cell tumours 5.4% (25
      patients). In 262 patients operated on account of lung cancer in stage I (pTNM)
      the probability of five-year survival was 49.2%, in patients in stage II 42.1%,
      in 158 patients in stage IIIa 20.9% (for all histological types combined). In 437
      patients after resection of the lungs on account of non-small-cellular carcinoma
      the probability of five-year survival was as follows: stage I 50.0%, stage II
      45.0%, stage IIIa 21.2%. CONCLUSIONS: The probability of five-year survival for
      the whole group of 462 patients in stages I, II and IIIa was 38.8%. The most
      important factor which influenced the probability of five-year survival was the
      stage of the disease. Neither age nor sex of the patients nor the histological
      type of the tumour had a statistically significant effect on the probability of
      five-year survival.

PMID- 9650344
TI  - [Calcium channel blockers in the treatment of hypertension and ischemic coronary
      disease. Conflicts in their evaluation].
AB  - Calcium channel blockers represent a pharmacologically non homogenic group.
      Verapamil and diltiazem have myocardial component of their effect, which acts
      against activated sympathicus. Short acting dihydropyridines (nifedipin) appear
      to be harmful by patients after myocardial infarction which is caused by the
      reflex sympathetic response to the predominant vasodilation. In the treatment of
      cardiovascular disease (e.g. hypertension, coronary vascular disease) are short
      acting dihydropyridines not recommended. Dihydropyridines of the new generation
      (amlodipin, felodipin, isradipin, lacidipin, nicardipin, nimodipin, nisoldipin,
      nitrendipin) induce less tachycardia due to their favorable kinetic features. If
      the slow movement in blood or at the receptor site is not a result of molecule
      features there is necessary to use retarded preparations of active substance.
      Nevertheless, commonly used retarded preparations fulfil this requirement only
      incompletely. The desirable quality is provided by modern form of retardation.
      (e.g. GITS) only.

PMID- 9650345
TI  - [Transmissible spongiform encephalopathy].
AB  - Transmissible spongiform encephalopaties (TSE) are a group of rare fatal diseases
      of humans and animals. Prions, small infectious proteinaceous particles, are
      their supposed cause. Prusiner's theory (Nobel price 1997) proves that
      pathogenetically active prions are conformated physiological prions but problems
      of pathogenesis of TSE are still open. Most important representative of human TSE
      is Creutzfeldt-Jakob's disease (CJD), that of animal TES is bovine spongiform
      encephalopathy (BSE). It seems that a new variant of CJD found in more than 14
      young people in the UK is in reality human BSE. Whether it means start of an
      epidemy of human BSE is not known.

PMID- 9650346
TI  - [Advances in the diagnosis and treatment of neuroblastoma].
AB  - Neuroblastoma is the second most common solid tumor in children. The prognosis is
      poor for approximately 70% of patients who have widespread disease at the time of
      diagnosis. The use of new strategies for classification and therapy has raised
      expectations for cure in advanced neuroblastoma. We summarise results and
      experiences reached during the last decade.

PMID- 9650347
TI  - [Prevalence of osteoporosis in the Czech Republic].
AB  - BACKGROUND: The objective of this study was to evaluate the prevalence of
      osteoporosis and osteopenia in Czech women and men aged 50 to 75 years. METHODS
      AND RESULTS: Bone mineral density was assessed in an age-stratified random sample
      of 713 women and 429 men from two cities (Prague and Litomerice) in the lumbar
      spine, proximal femur and total body by dual X-ray absorptiometry and in the
      distal forearm by single X-ray absorptiometry. The proportion of women and men in
      each age group with bone density below specified levels at any of these skeletal
      sites was projected to the population structure of the Czech Republic. With
      advancing age, in women at 55 years and in men at 65 years of age the population
      with normal bone mineral density becomes smaller, and a greater proportion has
      osteopenia or osteoporosis. Overall, an estimated 428,000 women and 195,000 men
      over age 50 have osteoporosis and another 680,000 women and 435,000 men have
      osteopenia. CONCLUSIONS: The results of this first population-based cross
      sectional study in the Czech Republic document a high prevalence of osteoporosis
      and osteopenia which is comparable with that published for the Netherlands and
      the United States. The results offer a basis for economical considerations in
      diagnosis, treatment and consequences of osteoporosis.

PMID- 9650348
TI  - [Trace elements in biological materials. Preanalysis safeguards].
AB  - In order to obtain objective information from estimations of trace elements (Al,
      As, Cd, Cr, Co, Cu, Pb, Li, Mn, Hg, Ni, Se, Zn) on deficiency or intake beyond
      the toxic limit it is necessary to pay attention among others also to
      preanalytical safeguarding, i.e. obtain all relevant information on the patient,
      ensure proper selection of material and sampling time, proper sampling and
      safeguarding the sample before the estimation proper. If the above rules and
      principles are respected, possible significant distortion on the results, which
      can be caused e.g. by contamination of the sample, can be prevented.

PMID- 9650349
TI  - The legacy of the Nuremberg Code.

PMID- 9650350
TI  - [Diuretics in the treatment of hypertension].
AB  - Diuretics belong into the group of basic antihypertensive drugs. A number of
      clinical trials provided evidence that long-term administration of diuretics
      leads not only to effective control of hypertension but has at the same time a
      favourable impact on cardiovascular morbidity and mortality. Along with beta
      blockers diuretics are recommended as drugs of first choice in patients with
      arterial hypertension. The author presents a brief account of different groups of
      diuretics incl. their indications.

PMID- 9650351
TI  - [Comment on the article by Z. Skodova et al: Decrease in cardiovascular disease
      mortality in the Czech Republic 1984-1993 and its causes].

PMID- 9650352
TI  - [Nitric oxide--its effects and significance in the human body].
AB  - Nitric oxide is a reactive gas with series of important functions in human body.
      An important deal of nitric oxide in the etiology and pathogenesis of series of
      autoimmune diseases, degenerative diseases of central nervous system etc. is
      suggested. This article summarizes the current knowledge about NO mean in
      medicine with impact to a perspective possibility of influence of any diseases by
      modulation of nitric oxide synthesis.

PMID- 9650353
TI  - [A new generation of dressings in the treatment of leg ulcers].
AB  - Current methods of topical treatment of leg ulcers are reviewed. Leg ulcers are
      chronic wounds in a trophically altered tissue that affects the healing capacity.
      Complete healing requires prolonged and rather expensive treatment and the
      patient is often disabled during this period. The conventional methods of
      treatment of leg ulcers, including various compresses, ointments, pastes and
      other topical drugs, that may possess a considerable sensitizing potential, are
      to an increasing extent replaced by updated therapy consisting in the use of a
      new generation of dressings. The latter include a number of materials that have
      been developed on the basis of recent knowledge of wound healing, such as
      hydrogels, hydrocolloids, xerogels, hydropolymer dressings, polyurethane foam
      sheets, alginate dressings, and non-adherent, non-woven cloth impregnated with
      silver and activated charcoal. The selection of the available materials must
      depend on the character and stage of the healing process. Each group of dressings
      exerts specific effects and none of them can recommended generally for the
      treatment of any types of ulceration. A brief survey of indications is given for
      each group to avoid their abuse.

PMID- 9650354
TI  - [Interleukin-6, tumor necrosis factor alpha and their soluble receptors in Bence
      Jones nephropathy. Possible role in pathogenesis andthe importance in the
      determination of prognosis in renal insufficiency].
AB  - BACKGROUND: Bence-Jones nephropathy, the most serious form of which is renal
      failure, is one of the frequent complications in multiple myeloma (MM). Precise
      pathogenetic mechanism of renal injury remains unclear. Experimental study points
      to the possible role of some cytokines in the development of this type of
      nephropathy. We have investigated the levels of interleukin-6 (IL-6), tumour
      nekrosis factor alpha (TNF-alpha) and their soluble receptors in patients with
      plasmocytoma. METHODS AND RESULTS: The group comprised 49 patients with
      plasmocytoma, mostly with MM. Significantly higher levels of IL-6 were found in
      patients with irreversible renal insufficiency and/or failure (group A-median
      13.3 pg/ml, range 3.6-33.3) comparing patients with reversible impairment (group
      B-median 3.1-range 1.8-38.4) (p < 0.01) and those with normal renal functions
      (group C-median 2.3-range 0.97-7.41) (p < 0.01). Significant difference was also
      found between the groups B and C (p < 0.05). Analysis of variance with the use of
      various factors showed that the correlation between IL-6 and prognosis of renal
      disease was stronger (p < 0.001) than the correlation between cytokine levels and
      the clinical phase of MM (p < 0.05). The difference of IL-6 levels between
      various clinical stages of MM was not significant. The levels of sIL-6R were
      significantly increased in patients with both reversible and irreversible renal
      insufficiency comparing the group with unaffected renal functions (p < 0.05 and p
      < 0.01 respectively). TNF-alpha levels did not differ between all 3 groups of
      patients, however, significantly increased values of sTNF-R II were observed in
      group A vs B and group B vs C (p < 0.05). CONCLUSIONS: We conclude, that some
      cytokines, especially IL-6/sIL-6R, could play an important role in development of
      renal insufficiency in MM or other monoclonal gammapathies. We suggest that IL-6
      levels could be predictive factor for renal insufficiency recovery.

PMID- 9650355
TI  - [Soluble cytokinin receptors in renal vasculitis and lupus nephritis].
AB  - BACKGROUND: Activation of various cytokines, e.g. TNF alpha, IL-1 and/or IL-6 may
      play important role in the pathogenesis of renal vasculitis and lupus nephritis
      (LN). Systemic effects of these cytokines may be modulated by their circulating
      soluble receptors. Plasma levels of cytokine receptors may thus be also markers
      of the activation of these cytokines. METHODS AND RESULTS: Plasma levels of TNF
      alpha, its soluble receptor p75 (sTNF-RII), IL-6 and soluble IL-6 receptor (sIL
      6R) were measured using ELISA in 17 pts with ANCA-positive renal vasculitis (12
      active-ANCA-A, 7 in remission ANCA-R), 9 pts with active lupus nephritis (LN) and
      5 healthy subjects. Pts with LN had in comparison with controls increased plasma
      levels of TNF alpha, sTNF-RII, IL-6 and sIL-6R. Pts with ANCA-A had also in
      comparison with controls increased plasma levels of TNF alpha, sTNF-RII and sIL
      6R, but plasma levels of IL-6 were not significantly increased dut to great
      standard deviation. Pts with ANCA-R had in comparison with controls increased
      plasma levels of sTNF-RII, but plasma levels of TNF alpha were in ANCA-R
      significantly lower than in ANCA-A. While the ratio TNF alpha/sTNF-RII was
      significantly lower in all groups of pts than in controls, the ratio IL-6R/sIL-6R
      was in comparison with controls significantly increased only in LN. CONCLUSIONS:
      While increased plasma levels of TNF alpha may be nonspecific marker of the
      activity of ANCA-positive renal vasculitis and LN, plasma levels of sTNF-RII are
      increased also in pts with ANCA-positive renal vasculitis in remission. Increased
      plasma levels of sTNF-RII may interfere with systemic effects of TNF alpha, but
      may also prolong the lifetime of its active form. Plasma levels of sIL-6R are
      increased both in ANCA-A and in LN, but their increase is, however, much less
      pronounced than that of sTNF-RII and cannot effectively block systemic effects of
      IL-6.

PMID- 9650356
TI  - [Dangerous religious sects].

PMID- 9650357
TI  - [Beta blockers in the treatment of arterial hypertension].
AB  - The authors present a detailed review on beta-blockers (BB) in the treatment of
      hypertension. In the introduction they deal with the organ distribution and
      effects of stimulation of adrenergic receptors, followed by a detailed
      classification of beta-blockers by selectivity and the presence of internal
      sympathetic activity (ISA or PAA). The mechanisms of the antihypertensive action
      of beta-blockers are due mainly to a reduction of the minute volume. However,
      other possible effects of BB are also mentioned. The authors discuss in detail
      the use of BB in hypertension and associated diseases, side-effects of BB,
      contraindications for their administration, possible interaction with other
      groups of drugs and the strategy of their use in patients with high blood
      pressure.

PMID- 9650358
TI  - [Spiral (helical) computer tomography].
AB  - The introduction of spiral (helical) computed tomography (CT) has revolutionized
      the way established body CT examination are performed and has created new
      examinations as CT angiography. The production of overlapping images from single
      short X-ray exposure, the minimization of motion artefact and the suppression of
      respiratory misregistration have all improved performance of routine CT
      examinations. These same technical advantages have also led to the development of
      new applications. With advanced 3-D postprocessing applications, simulated
      endoscopy is made possible permitting the radiologist the view anatomy from
      within any lumen or anatomic space within the body.

PMID- 9650359
TI  - [Chronic fatigue syndrome].
AB  - A great concern is recently given to the chronic fatigue syndrome in the Czech
      Republic. Unfortunately, published data allow us to state neither the etiologic
      agent nor the pathophysiology of the disease. Although many authors published
      various laboratory abnormalities, these changes are inconstant and do not allow
      to state a diagnosis of the chronic fatigue syndrome by a single laboratory test,
      and effective therapy is not known either. Psychotherapy, and in some cases
      antidepressants, are recommended by some authors to alleviate patient's symptoms.
      Neither immunological nor antiviral therapy showed positive results in controlled
      trials and are not generally used in most centers.

PMID- 9650361
TI  - [What was not included in the recommendations for the diagnosis and therapy of
      hyperlipoproteinemia in childhood].
AB  - Screening and treatment of hyperlipidaemia should be the concern of
      paediatricians. This is suggested by the finding of fatty streaks and other
      atheromatic changes in children. The authors prefer selective to nationwide
      screening in children who have close relatives with coronary heart disease or
      cerebral haemorrhage before the age of 55 years in men and 65 years in women or
      elevated total cholesterol levels. In case of repeated total cholesterol levels
      of 4.4-5.2 mmol/l the authors recommend annual, in case of levels above 5.2
      mmol/l 3-6 month intervals between examinations. The authors found values above
      5.2 mmol/l in one quarter of otherwise healthy children. In addition to the
      hyperlipidaemic theory there is the infectious theory of development of
      atherosclerosis and the theory of programming of coronary heart disease during
      pregnancy. By dietary and lifestyle provisions it is possible to reduce
      hyperlipidaemia in the great majority of children. In boys above 10 years and
      girls above 20 years resins are indicated if the total cholesterol level is above
      8 mmol/l.

PMID- 9650360
TI  - [The effect of pharmacologic prophylaxis with Panpal on acetylcholinesterase
      activity in the diaphragm and various parts of the brain in rats during treated
      and untreated Soman poisoning].
AB  - BACKGROUND: The pharmacological prophylaxis protecting the organism against
      organophosphorus compounds could increase the effect of antidotal treatment of
      poisoning with organophosphates. METHODS AND RESULTS: The influence of the
      pharmacological prophylaxis with Panpal (pyridostigmine in combination with
      benaetyzine and trihexyphenidyle) on acetylcholinesterase activity in diaphragm
      and various parts of brain at 1 and 3 h following non-treated and treated (the
      oxime HI-6 in combination with atropine) soman poisoning was tested on male rats.
      While Panpal did not significantly influence the acetylcholinesterase activity in
      brain following non-treated as well as treated soman poisoning. Panpal increased
      so many-induced acetylcholinesterase inhibition following non-treated poisoning
      and decreased the reactivating effect of the oxime HI-6 following treated soman
      poisoning in diaphragm. CONCLUSIONS: Our data confirm the importance of the
      combination of reversible acetylcholinesterase inhibitor pyridostigmine with
      anticholinergic drugs in the pharmacological prophylaxis of soman poisoning
      because of the elimination of consequences of pyridostigmine-induced increasing
      in acetylcholinesterase inhibition in the peripheral compartment.

PMID- 9650362
TI  - [Hypertensive crisis and its treatment].
AB  - Hypertensive crises threaten, due to the rapid rise of blood pressure the
      patient's life by cerebral, cardiovascular and renal complications. It may cause
      left-sided heart failure, dissection of the aorta, cerebral haemorrhage, renal
      failure. Patients with hypertensive crises are admitted to intensive care units
      with the possibility of systematic monitoring of the pulse rate, BP, ECG,
      diuresis and other vital functions. Treatment is started immediately by
      injections (usually i.v.) of antihypertensive drugs while monitoring the BP,
      vital functions and the general condition. At first small amounts of
      antihypertensives are administered and, depending on the BP, the dosage is
      adjusted. The recommended safe drop of BP which should be achieved within one
      hour is 100-110 mm Hg of diastolic BP or a 20% drop of the initial pressure.
      Concurrently with injections oral administration of antihypertensives is started.
      Correct treatment leads in the majority of patients to regression of hypertension
      and of acute danger to the patient's life. On the other hand, inadequate
      treatment threatens the patients with fatal complications.

PMID- 9650363
TI  - [The Christian search for health and treatment of illness].
AB  - The link between Euro-American medicine and Christian ways of thinking is
      essentially beyond doubt. Deviations from and tension between so-called mundane
      philosophy of health and disease and theological views ensure rather from
      bilateral non-communication and isolation. Christian thinking owes the world more
      profound and more up-to-date study of anthropological and biological problems.
      The philosophy of medicine needs also innovations and more convincing spiritual
      foundations.

PMID- 9650365
TI  - [Practical experience in providing pharmaceutical services in public pharmacies
      in Denmark].
AB  - The paper evaluates practical activities of the public pharmacy in Denmark, which
      materialize the content of the so-called pharmaceutical care in everyday contacts
      of the pharmacist and patients. It has been found that the conception of
      pharmaceutical care is materialized in somewhat different ways in different
      countries and in different types of establishments (clinical pharmacy--public
      pharmaceutical service). The Czech pharmaceutical service could link up with the
      tradition of the 1970s and 1980s when there were efforts to make pharmacist's
      work more effective, aiming at solving the patient's problems concerning
      medication. This is a world-wide trend worth joining.

PMID- 9650366
TI  - [Relation between chemical structure and antimycobacterial activity against
      atypical strains. XIII. Thiosalicylanilides].
AB  - On the basis of a preliminary study of antimycobacterial activity of
      thiobenzanilides a series of eight thiosalicylanilides have been prepared.
      Synthetized compounds have been examined in vitro against Mycobacterium
      tuberculosis, Mycobacterium kansasii, Mycobacterium avium and Mycobacterium
      fortuitum. All compounds have been found very active. The values of minimal
      inhibitory concentrations are summarized in Table 1. 3',4'-Salicylanilide was
      selected for the following research. The compound have been found inactive in
      vivo (on experimental murine tuberculosis).

PMID- 9650367
TI  - [Azabischalcones--a new class of potential antitubercular agents].
AB  - A series of substituted azabischalcones Ia-Ip, monochalcone II and
      dihydroxyderivative III has been prepared and examined for their in vitro
      activity against Mycobacterium tuberculosis, Mycobacterium kansasii,
      Mycobacterium avium, Mycobacterium fortuitum as well as INH-resistant strains.
      Several compounds under study have the same activity as INH and greater than PAS,
      Contebene, Ethionamide. The results are summarized in Table 1. In the case of
      compound Ie, its in vivo activity was studied against M. tuberculosis as well
      (see Table 2). The toxicity of compounds under study is very low--2000
      mg/kg/mouse.

PMID- 9650368
TI  - [Antiedematous activity of certain arylcarboxylate copper aquacomplexes].
AB  - Using rat paw carrageenan edema, the anti-inflammatory activity of nine selected
      arylcarboxylatocopper(II) aquacomplexes of the general composition
      Cu(RCOO)2.nH2O, where R represents 2-hydroxy-Y-methylphenyl, Y = 3 (n = 1.5), 4
      (4) or 5 (2); 2-hydroxy-3,6-dimethylphenyl (n = 4); 2,5-diacetoxyphenyl (1); 2
      methoxy-(1) and 4-methoxyphenyl (3); 2-furyl (3) and 2-thienyl (1), was assayed
      and compared to that of the free acids. Copper(II) salicylate tetrahydrate and
      salicylic acid were used as standards for comparison. All compounds were applied
      i.p. in a single dose of 50 mumol/kg body weight, calculated for the RCOO
      fragment. m-Cresotato- (mean edema reduction 70%) and p-cresotatocopper(II) (80%)
      aquacomplexes were clearly more effective than copper(II) salicylate tetrahydrate
      (55%). The nonsubstituted hydroxyl of the salicylate skeleton of acidoligands is
      required for the activity of the complexes and of free acids tested. Isomeric
      cresotic acids (82-47-62%) and 2-furoic acid (48%) exhibited a higher effect than
      salicylic acid (42%). The relationship between the coordination-chemical
      properties and the biological effects of the complexes studied is discussed.

PMID- 9650369
TI  - [Topical preparations for burns and their evaluation].
AB  - The study focused on some problems connected with the formulation of the topical
      preparation of the hydrocream type, intended for the treatment of dermal burns.
      Seven cream bases containing Emulgator E 2155, Polysorbate 80 and silicone oils
      were evaluated. The employed drugs included carbizocaine, lidocaine,
      chlorohexidine, and the immunomodulating substance glucan. A measurement of the
      surface tension of chlorohexidine and carbizocaine did not reveal interaction
      between these two drugs. Liberation tests confirmed a higher release of lidocaine
      in comparison with carbizocaine and chlorohexidine. The silicone oil present did
      not influence the release of carbizocaine, but it promoted the release of
      lidocaine and chlorohexidine. The determination of rheological parameters
      revealed that an addition of drugs influenced the flow properties of creams. The
      suitability of cream ointments was evaluated on the basis of their drying.

PMID- 9650371
TI  - [Analysis of the activities of the Information Service of the National Institute
      for Drug Control].
AB  - An analysis was carried out concerning the questions regarding drug information
      solved by the information service section of the State Institute for Drug Control
      (SUKL) in 1992-1995. A rapid decrease in the number of questions was observed
      during the period under study. This trend was mainly caused by a decline in
      questions regarding the availability of drugs in the market. Questions were posed
      in a similar ratio by physicians and pharmacists predominantly from Prague and
      surrounding areas. Questions from other categories of health-care professionals
      and the lay public are in minority. Most questions focus on the characteristic of
      the drug and its availability. AISLP, Martindale and Rote Liste serve as the
      principal information sources.

PMID- 9650370
TI  - [HPLC analysis of nonsteroidal antirheumatic agents in biological materials. III.
      Pyrazolidinediones].
AB  - The present paper surveys published HPLC methods estimating pyrazolidinediones in
      biological materials and an HPLC method for estimation of kebuzone in the samples
      of whole blood, isolated erythrocytes and plasma. An addition of propyl gallate
      prevented undesired oxidation of kebuzone. For liquid-liquid extraction, kebuzone
      was analysed on the reverse phases Separon SGX C-18 with the mobile phase
      methanol--water (pH 2.7) and detected at 247 nm. The elaborated method was used
      in a pharmacokinetic study of kebuzone on rabbits.

PMID- 9650372
TI  - [Antiedema activity of selected compounds with a gallate skeleton].
AB  - Using rat paw dextran-induced and carrageenan-induced edemas, the anti
      inflammatory activity of gallic acid (I), triacetylgallic acid (II) and
      monohydrate copper(II) triacetylgallate (III) was assayed. All compounds tested
      were applied i.p. in a single dose of 50 mumol/kg body weight, calculated for the
      RCOO-fragment. The average antiedematous activities in dextran/carrageenan edemas
      were decreasing in the following order: III (55.9/41.8%) > I (38.6/31.1%) > II (
      3.4/13.3%). The relationship between the biological effects found and gallic acid
      as well as its structural derivatives is discussed.

PMID- 9650373
TI  - A comparison of three preinduction cervical priming methods: prostaglandin E2
      gel, Dilapan S rods and Estradiol gel.
AB  - The aim of the study was to evaluate the efficacy of three cervical priming
      methods. From January 1, 1994 to December 31, 1996 247 patients presenting an
      indication for induction of labor with an unripe cervix were randomly assigned to
      one of the following preinduction protocols: 0.5 mg of Prostaglandin E2 gel
      administered intracervically (n = 83), four hygroscopic Dilapan S rods applied
      intracervically (n = 82), and 150 mg of Estradiol gel administered intravaginally
      (n = 82). The inclusion criteria were the patient's informed consent, singleton
      pregnancy of more than 36 weeks, cephalic presentation, Bishop score < 5 points
      and reactive non-stress test. If the cervical maturation (Bishop score > or = 5,
      and/or Bishop score augmentation by 2 points) did not occur after 14 hours of
      priming, the case was considered a failure. In the opposite case the patient was
      induced by means of extraamniotic PGE2 administration. The mean gain in the
      Bishop score was 3.7 points in the PGE2 group 3.9 points in the Dilapan S group,
      and 2.8 points in the Estradiol group. 71 patients (85.5%) were successfully
      preinduced in the PGE2 group, 73 (89.0%) in the Dilapan S group, and 63 (76.8%)
      in the Estradiol group. Labor was induced by preinduction only in 23 patients
      (31.3%) of the PGE2 group in 17 (20.7%) of the Dilapan S group, and in 14 (17.1%)
      of the Estradiol group. The mean induction to delivery interval was 7 h 27 min in
      PGE2 group, 7 h 49 min in the Dilapan S group and 9 h 15 min in the Estradiol
      group. The Caesarean section rate was 24.4% in the PGE2 group, 10.5% in the
      Dilapan S group, and 24.4% in the Estradiol group. PGE2 gel and Dilapan S rods
      proved higher efficacy than Estradiol gel. The highest frequency of labor induced
      by preinduction only was in the PGE2 group. There were shorter induction to
      delivery intervals in the PGE2, and Dilapan S groups. The lowest Caesarean
      section rate was in the Dilapan S group. Neither serious side effects nor
      negative neonatal outcome were noted in either group.

PMID- 9650374
TI  - [Personal experience with diagnosis of complete hydatidiform mole based on DNA].
AB  - In our study we analyzed 13 cases of histologically defined complete hydatidiform
      mole (CHM), by using cytogenetic and molecular genetic methods. There were seven
      homozygous and six heterozygous CHM. In one case of heterozygous CHM we found a
      biparental contribution to genomic DNA. This is evidence of a more heterogeneous
      etiopathogenesis of hydatidiform mole.

PMID- 9650375
TI  - [MESA, TESA, TESE + ICSI: results of the first 50 cases].
AB  - During the period between February 1996 and August 1997 51 infertile men were
      operated. The authors evaluate the results from 47 couples--25 cases of
      testicular azoospermia and 22 cases of obstructive azoospermia. The mean age of
      the men in the group was 33 years (22-48 years). The follow-up period is 1-18
      months. In 17 cases, microsurgical epididymal sperm aspiration (MESA) was made,
      in five cases testicular sperm aspiration (TESA) and in 25 men, testicular sperm
      extraction (TESE) was performed. In the group with testicular azoospermia it
      proved possible to obtain sperm in 12 of 25 cases, i.e. in 48%. In men with
      obstructive azoospermia all aspirations were successful, i.e. the yield was 100%.
      In this group five children were born, seven pregnancies are under way. Thus
      regardless of the etiology of male infertility 12 of 47 cases, i.e. 25.5% were
      resolved successfully. When the results of the two groups are differentiated, the
      outcome is as follows: in the group with testicular azoospermia one child was
      born and two pregnancies are under way, i.e. 12%, in the group with obstructive
      azoospermia four children were born and five pregnancies are under way, i.e.
      40.9%.

PMID- 9650376
TI  - [Clinico-teratologic counseling and the Teratology Information Service].
AB  - Medical records of 1179 pregnant women counselled at the Department of Medical
      Genetics Klimentska during the period 1990-1995 because of exposure to
      medicaments during the preconception period and in the first trimester were
      analyzed. Women exposed to antimicrobial agents prevailed (48 per cent). Most
      frequent was treatment with Doxycycline, Co-trimoxazole and Metronidazole. 23 per
      cent of women were exposed to sex hormones, most frequently to oral
      contraceptives and norethisterone. The average gestational age at exposure to
      antimicrobial agents was 21.5 days and 30 days at exposure to sex hormones.
      Specific features of clinical-teratological counselling and the role of the Czech
      Teratologic Information Service are described.

PMID- 9650377
TI  - [Occurrence of diaphragmatic hernia in the Czech Republic 1961-1995].
AB  - During 1961-1995 the incidence of diaphragmatic hernia on the territory of the
      Czech Republic was investigated. From a consecutive series of 5,137,907 births
      during the period from 1961-1995 in the Czech Republic 1242 cases of
      diaphragmatic hernia were diagnosed, incl. 1233 in born children; 9 were
      diagnosed prenatally and the pregnancies were terminated. The mean incidence of
      diaphragmatic hernia in born children during the investigation period was 2.36
      per 10,000 liveborn infants and when the prenatally diagnosed cases were added,
      the mean incidence was 2.39 per 10,000 liveborn infants.

PMID- 9650378
TI  - [Occurrence of urinary bladder exstrophy in the Czech Republic 1961-1995].
AB  - During the period from 1961-1995 the incidence of extrophy of the urinary bladder
      was investigated on the territory of the Czech Republic. From a consecutive
      series of 5,137,907 infants born in the Czech Republic in 1961-1995 65 cases of
      this defect were diagnosed. The mean incidence of extrophy of the urinary bladder
      in born children during the investigation period was 0.14 per 10,000 liveborn.
      Nationwide data on the prenatal diagnosis of this defect during the investigation
      period are not available so far.

PMID- 9650379
TI  - [The importance of hormone receptors in benign breast diseases].
AB  - Benign breast lesions are usually divided with regard to the proliferative
      activity into three categories. These lesions, depending on their
      histopathological characteristics and correlation with epidemiological studies
      differ as to the risk of breast cancer. 1. The concentration of hormonal
      receptors in the breast tissue in our group correlated with the proliferative
      activity of the lesion. 2. A major proliferative lesion and atypical hyperplasia
      of the ductal epithelium are a typical precancerous condition. 3. The hormonal
      receptor concentration defines, in addition to the histological classification,
      the biological activity more accurately. The prevalence of the oestrogen receptor
      or its trend to predominate over the progesterone receptor is a serious marker of
      imminent cancerogenesis. 4. Based on the prevalence of hormonal receptors it is
      possible to select suitable hormonal treatment to suppress the proliferative
      potential of the breast lesion. 5. A high level of the oestrogen receptor in non
      malignant formations of the breast can be considered a manifestation of increased
      sensitivity of this target tissue to circulating oestrogens. It is a question
      whether it is the manifestation of mutation of the oestrogen receptor or the
      consequence of long-term exposure to uncovered levels of bioavailable oestrogens.

PMID- 9650380
TI  - [Pregnancy outcome and perinatal results in a group of women treated with
      fertilization in vitro and embryo transfer].

PMID- 9650381
TI  - [The Schaut radical vaginal hysterectomy with laparoscopic pelvic
      lymphadenectomy].

PMID- 9650382
TI  - [Ultrasonography of the uterus in the diagnosis of pathologic states of the
      endometrium and uterus].

PMID- 9650383
TI  - [Ultrasound findings and revision of the uterine cavity after labor].

PMID- 9650384
TI  - [Chromosome markers and balanced translocation in the etiology of infertility].

PMID- 9650385
TI  - [Adenomyosis as a possible manifestation of long-term treatment with tamoxifen].

PMID- 9650386
TI  - [Pregnancy and labor in Leyden-Moebius myodystrophy].

PMID- 9650387
TI  - [Prevention of congenital toxoplasmosis].

PMID- 9650388
TI  - [Sirenomelia: the sequence of undevelopment of cloacal membranes].

PMID- 9650389
TI  - [Prediction and detection of ovulation in clinical practice].

PMID- 9650390
TI  - [Endometriosis].

PMID- 9650391
TI  - [Surgical treatment of endometriosis].

PMID- 9650392
TI  - [Surgical procedures using hysteroscopy].

PMID- 9650393
TI  - [Experience with diagnostic and therapeutic hysteroscopy].

PMID- 9650394
TI  - [Importance of laparoscopy in vaginal hysterectomy].

PMID- 9650395
TI  - [Laparoscopic hysterectomy of the enlarged uterus: an advanced vaginal technique-
      retrospective analytic study].

PMID- 9650396
TI  - [Laparoscopic lymphadenectomy and hysterectomy in the treatment of endometrial
      carcinoma].

PMID- 9650397
TI  - [Registry of complications in gynecologic laparoscopy--initial results-
      complications of laparoscopic vaginal hysterectomy].

PMID- 9650398
TI  - [Personal experience with laparoscopic hysterectomy].

PMID- 9650399
TI  - [Laparoscopic management of gynecologic malignancies--controversies].

PMID- 9650400
TI  - [Diagnosis of endometrial pathology in postmenopausal women].

PMID- 9650401
TI  - Ethical issues in gynecology.
AB  - The authors apply the language and concepts of ethics to the problem of
      differences between the gynecologist and the patient about what is in the
      patient's interest. We develop a framework for clinical judgment and decision
      making about the ethical dimensions of the gynecologist-patient relationship. To
      achieve this goal we define the ethical principles of beneficence and respect for
      autonomy. We then show how these two principles interact in clinical judgement
      and decision making using common examples from gynecologic practice. We examine
      factors that influence the relative weight of these principles, including subject
      matter, probability of net medical benefit, availability of reasonable
      alternatives, and ability of the patient to participate in the informed consent
      process.

PMID- 9650402
TI  - [The National Register for Assisted Reproduction: results and analysis of
      complications].
AB  - 1. Analysis of achieved results of assisted reproduction provides evidence of a
      steadily increasing success of ART methods in the Czech Republic. 2. Analysis of
      results and complications makes it possible a) to prove optimal therapeutic
      procedures in different groups of patients b) to recommend preventive measures to
      avoid complications c) assess possible side-effects on women and the foetus.

PMID- 9650403
TI  - [Reduced serum dehydroepiandrosterone levels in postmenopausal osteoporosis].
AB  - The decline of the production of several hormones with age has been recently
      linked to several degenerative processes related to aging including osteoporosis.
      The aim of our study was to confirm the observations published in 1994 suggesting
      that postmenopausal women with DHEAS levels below a certain limit have a much
      higher risk of osteoporosis than those with the levels above this limit. The
      DHEAS levels were measured by RIA and compared to our own age-adjusted reference
      ranges. The values lower than 25th quantile were considered "subnormal". More
      than 500 postmenopausal subjects were included in our study. In those with
      "subnormal" levels bone mineral density (BMD) was measured on DEXA (Lunar or
      Hologic). Decreased BMD ranging from osteopenia to severe osteoporosis was found
      in 86% of 74 women with "subnormal" DHEAS, while the expected frequency in our
      postmenopausal population may be about 30%. In the following period the serum
      DHEAS levels were compared with DEXA findings in another 134 postmenopausal
      women. The DHEAS levels in all stages of decreased BMD were significantly lower
      than those in the group with normal BMD. The clinical sensitivity and specificity
      of DHEAS as a marker of increased risk of osteoporosis has been calculated for a
      cut-off limit of 0.5 MoM. In the light of these findings we believe that the
      robust and relatively cheap DHEAS determination could help us to identify women
      who are at higher risk of osteoporosis. Also, in the future, only the women with
      evidently deficient DHEA production might possibly become candidates for eventual
      DHEA substitution.

PMID- 9650404
TI  - [The biology of menopause].

PMID- 9650405
TI  - [The role of the vascular endothelium and reactive forms of oxygen and nitrogen
      in the pathogenesis of preeclampsia].

PMID- 9650406
TI  - [Pfannenstiel--a software program for video documentation of surgical records in
      gynecology].

PMID- 9650407
TI  - [Laparoscopy in chronic pelvic pain].

PMID- 9650408
TI  - [Importance of vaginal sonography and curettage in the diagnosis of dysfunctional
      hemorrhage].

PMID- 9650409
TI  - [Primary vaginal carcinoma].

PMID- 9650410
TI  - [Use of variable number of tandem repeat polymorphism in assessing correct
      sampling in prenatal diagnosis of monogenic disorders].

PMID- 9650411
TI  - [Current laws on venereal diseases: notification of sexual diseases, contact with
      laboratories, serology of lues, culture and diagnosis of gonorrhea, recourse in
      noncompliance, isolation in health care facilities].

PMID- 9650412
TI  - [Adenosarcoma of the uterus in a 19-year-old patient].

PMID- 9650413
TI  - [Recent and old history of the Czech Gynecologic and Obstetrical Society].

PMID- 9650414
TI  - [Professor Karel Klaus--a classical figure in Czech obstetrics].

PMID- 9650415
TI  - [Review of the molecular genetics of the Lynch syndrome].
AB  - The molecular genetics of the hereditary nonpolyposis colorectal cancer (HNPCC,
      Lynch syndrome) is reviewed. Recently, four genes (hMSH2, hMLH1, hPMS1, hPMS2)
      whose mutations are related to HNPCC were discovered. The products of these genes
      are homologues of the bacterial mismatch repair (MMR) system proteins MutS and
      MutL. Dysfunction of MMR system both in bacterial and human cells leads to the
      microsatellite instability (MI) in repetitive sequences of DNA. These sequences
      are also present in some tumor suppressor genes (e.g. TGF-beta RII or BAX).
      Therefore, the MI probably leads to the impairment of the cell cycle regulation
      and a carcinoma can develop from the clone of such cells with nonregulated
      growth.

PMID- 9650416
TI  - [Hormonally active peptides].
AB  - The article reviews hormonally active peptides, mechanisms of their biosynthesis
      and chemical synthesis. Special attention is given to achievements of the Czech
      school of peptidology. Mechanisms of activity of peptidergic hormones is based
      mainly on the activation of adenylatcyclase and formation of the "second
      messenger", cAMP. Other three possible mechanisms are also reviewed. Main groups
      of peptidergic hormones (neurohypophyseal hormones, hypothalamic regulatory
      hormones, gastrointestinal hormones, natriuretic peptides, and many others) are
      described and their therapeutic and diagnostic significance is summarised. Future
      prospects of peptidology in the clinical praxis are briefly reviewed.

PMID- 9650417
TI  - [Intracranial hypertension].
AB  - Intracranial hypertension is a serious consequence of the impaired intracranial
      volume homeostasis. It can be encountered in practically all fields of clinical
      praxis. The article reviews bibliographic data of the mechanisms of the
      intracranial hypertension development: Intracranial expansion, Brain edema,
      Hemodynamic brain edema, Liquor accumulation--hydrocephalus. A pathophysiological
      approach to the hypotheses of edema and brain swelling is stressed. Outlines of
      the modern diagnostics and therapy of the intracranial hypertension are
      presented.

PMID- 9650419
TI  - Neuronal connections, cell formation and cell migration in the perinatal human
      hippocampal dentate gyrus.
AB  - Jean Piaget's "stage theory" suggests that cognitive development proceeds in
      discrete steps, among which the first is the sensorimotor period that occupies
      the first two years. In recent years it became clear that an intact and mature
      hippocampus is necessary for memory formation both in experimental animals and in
      human. In the present experiments the perinatal morphological development of the
      human hippocampus was studied to describe structural changes that may correlate
      with the developmental changes of intellectual growth. Our results suggest that
      cell formation in the human hippocampus terminates several weeks before birth,
      but immature cells migrate to their final positions through the first six
      postnatal months. The newborn hippocampus contains all cell types and cell layers
      that are characteristic for the adult hippocampus. However, changes of the light
      microscopic features of the postsynaptic target neurons of hippocampal granule
      cells indicate that connections between granule cells and their target neurons
      are immature at birth and develop through an extended period of time that may
      last for three years. Since this neuronal connection is the first link in the
      chain of the main hippocampal synaptic circuitry, it may be suggested that human
      hippocampus is functionally impaired at birth. This period of light microscopic
      morphological maturation correlates well with the time period of Piaget's first
      stage of cognitive development. It can also be suggested that the prolonged
      postnatal development of some neuronal circuitries in the human hippocampus may
      be responsible for the psychological phenomenon of "infantile amnesia", that is
      the lack of memory traces from the early postnatal period.

PMID- 9650420
TI  - Protective effect of flavonoids and tocopherol in high altitude hypoxia in the
      rat: comparison with ascorbic acid.
AB  - The mixture of flavonoids (silymarin) from Carduus Marianus (0.9 mg.g-1 body
      weight) and/or ascorbic acid (0.4 mg.g-1 body weight) were administered in the
      food to 21 day-old (b.w. 35-45 g) rats for one week. Then the animals were
      exposed, in a hypobaric chamber, to simulated altitude 8,000-12,000 m for one
      hour. Mean lethal altitude was calculated by the Behrens equation: it was 10,150
      m in controls, 10,550 m in ascorbic acid treated, 10,500 m in silymarin and
      tocopherol treated and 10,450 m in animals, receiving both ascorbic acid and
      silymarin. Thus silymarin protected the animals against lethality of high
      altitude hypoxia. The effect of ascorbic acid and silymarin were not additive.

PMID- 9650421
TI  - On the intrinsic mechanisms of spontaneous motility in chick embryos.
AB  - Our experimental study was aimed on the problems of co-operation of NMDA- and NO
      ergic mechanisms in the genesis of spontaneous motility in 17-day-old chick
      embryos. 1. Blockade of NO-synthase (NOS) by 7-nitro indazole prevented effect of
      an activation cocktail (NMDA + L-arginine). 2. Simultaneous blockade of NOS and
      of polyamine site in NMDA-receptor by arcaine was revealed by increased NMDA
      activation of the spontaneous motility and by blockade of L-arginine and cocktail
      effects. 3. The blockade of NMDA-activation, depression of L-arginine activation
      and short-lasting potentiation of cocktail effect. 4. Blockade of NMDA mechanism
      by Mg2+ abolished activatory effect of both NMDA and L-arginine. The initial
      activation remained from the cocktail effect only. Results were considered as an
      evidence of a possible co-operation among NMDA- and NO-ergic mechanisms in the
      development of the embryonic spontaneous motility.

PMID- 9650422
TI  - [Developmental neuronal plasticity and its importance in the recovery and
      function of neural tissue].
AB  - Plasticity is understand as a natural ability of the nervous tissue to respond to
      intrinsic and extrinsic stimuli by means of functional or structural changes. All
      its manifestations, including the developmental changes and processes of recovery
      are controlled by general genetic programs. One of the major research goals in
      the field of neuroplasticity is to design a strategy for the activation of the
      functional recovery. Enough evidence has shown that the internal environment of
      the nervous tissue is one of the decisive factors which determine the degree of
      both the developmental and regenerative plasticity. To improve capacity for the
      recovery it is therefore necessary to activate these intrinsic neuroplastic
      mechanisms. One alternative is the method of implantation of the embryonal nerve
      cells suspension into the site of neuronal lesion. The grafted cells can either
      replace the lost cells or they might become a source of stimulating factors which
      may activate the process of recovery. In the model of the intrahippocampal
      pathways interruption (experimental partial elimination of granule cells in the
      dorsal blade of the dentate gyrus), the subsequent implantation of embryonal
      neurons of the same origin into the site of lesion can partly restore the
      structural pattern of the gyrus dentatus and probably preserve some of the
      afferent connections. However, the outgrow of efferent fibers probably remains
      limited to the grafted tissue.

PMID- 9650423
TI  - [Intermittent hypobaric hypoxia during development--morphologic changes in the
      neocortex and hippocampus].
AB  - Infant rats, together with their mother, were exposed to the simulated altitude
      of 7,000 m for 8 hours per day since birth to the age of 18 days. Animals were
      studied the 25th day, 7 days after the last exposure to hypoxia. The experimental
      and control animals were killed the 25th day by the transaortic perfusion with 4%
      buffered neutral formaldehyde under ether anaesthesia. Brains were processed for
      classical neurohistological analysis (Nissl staining). 1. Cortical area in the AP
      plane 3 mm posterior to bregma were subjected to quantification and "laminar
      analysis" of the neuron count. 2. Hilus of the dentate gyrus between the AP plane
      2.5 mm and 4 mm posterior to bregma were subjected to quantification of the
      neurons. The findings were as follows: a) The cytoarchitectonics of the brain in
      animals exposed to hypoxia was not severely damaged. b) The thickness of
      neocortex is in the experimental animals lower than that in the controls. c) The
      "laminar analysis" of neocortex showed a relative increase of neuronal density in
      layers I., II., V. and VI. of the cortex. d) The quantification of the neuron
      count showed a decrease in hilus of the dentate gyrus. These results demonstrate
      that the intermittent hypobaric hypoxia has a profound effect on morphological
      maturation of central nervous system in infant rats.

PMID- 9650424
TI  - [Postictal depression in 12-day-old animals].
AB  - Postictal depression systematically follows epileptic after-discharges (AD)
      evoked from many different regions of the brain of adult animals. In presented
      experiments we tested by evoking ADs from sensorimotor cortex whether the
      susceptibility to undergo postictal depression is age-dependent and whether it
      correlates with the individual duration of ADs. Groups of 12-, 18- and 25-day-old
      male rats were used (freely moving animals--semichronic preparations; six trains
      of rhythmic electrical stimulations in one min. intervals after the end of
      previous seizure; EEG recordings; durations of ADs were measured). In the whole
      group of the 25-day-old animals the mean duration of ADs after individual
      stimulations illustrated the inhibitory influence of the first seizure on the
      duration of all subsequent ADs. In 18-day-old animals the depression was less
      pronounced and in 12-day-old it seemed to be not present. Analysis of results in
      individual animals in the group of youngest animals showed, that duration of
      pairs of subsequent seizures was related to the duration of the first of them.
      Also in this age group long seizures caused postictal depression. Duration of
      seizures seems to vary individually and it strongly influences the mean results
      of the whole group. The differences between the groups could be explained on the
      basis of the different pattern of ADs in young and older animals. In young
      animals the total "output" of seizure is low and it could also cause not so
      intensive and long posttetanic depression based on changes of intracellular Ca2+,
      because this form of synaptic plasticity seems to involve the activation of
      Ca(2+)-dependent protein kinases. Synaptic energy consumption also may play some
      role in postictal depression occurrence.

PMID- 9650425
TI  - [Morphologic and functional characteristics of an animal model of cerebellar
      degeneration (lurcher mutant mice)].
AB  - Lurcher mutant mice are characterized by genetically determined degeneration of
      cerebellar Purkinje cells, granule cells and inferior olivary neurons (ION). In
      the morphological part of this study Lurcher mutant and wild type mice were given
      intraperitoneal injections of 3-acetylpyridine (3AP) to look at the effect of
      this neurotoxin and niacinamide antagonist on the ION. Intraperitoneal
      administration of 3AP is characterized by the different sensitivity of ION in
      Lurcher mutant mice and wild type mice in both infant and young adult animals.
      Lurcher mutants suffered a destruction of these neurons while wild type mice were
      unaffected. Since the cerebellum plays an essential role in the sphere of motor
      learning and behavior, in the functional part of this study we investigated some
      characteristics of early learning in Lurcher mutant and wild type mice. The first
      experimental results show some differences in the inhibitory reaction of the
      passive avoidance between Lurcher mutant and wild type mice in early ontogeny,
      during the first month of their life. Both morphological and functional findings
      show not only different effects of 3AP on genetically mutated and wild type mice
      in the same inbred strain but also some functional changes in the sphere of early
      learning and memory as well.

PMID- 9650426
TI  - [Pathophysiology: the past, present and future].

PMID- 9650427
TI  - Prostate cancer: local staging with endorectal magnetic resonance imaging.
AB  - BACKGROUND: Prostate cancer has received increasing attention during the past
      decades. Staging of tumors before treatment is imperative for planning
      appropriate therapy. The purpose of this study is to assess the role of
      endorectal magnetic resonance imaging (MRI) in local staging of prostate cancer.
      METHODS: Endorectal MRI was performed in 31 patients with histologically-proven
      prostate cancer. MRI was done three to 100 days (mean, 32.1 days) after either
      transrectal ultrasonography (TRUS) with biopsy or transurethral resection of the
      prostate (TURP). Radical prostatectomies were performed within two weeks after
      MRI. The diagnostic accuracy of endorectal MRI for local tumor staging,
      specifically for extracapsular extension (ECE) and seminal vesicle invasion
      (SVI), was evaluated by correlating MRI results with histopathologic findings of
      whole-mount specimens. RESULTS: The accuracy of endorectal MRI for the detection
      of tumor presence and estimation of tumor volume was 48%. Sensitivity,
      specificity and positive predictive value for evaluation of ECE were 88%, 69% and
      80%, respectively, and for SVI, were 66%, 84% and 50%, respectively. The overall
      accuracy of MRI in local tumor staging (using the TMN system) was 61%. Accuracy
      in differentiating localized from invasive cancer was 84%. CONCLUSION: Endorectal
      MRI is not accurate enough to detect tumor presence or estimate tumor volume.
      Diagnostic accuracy for local tumor staging is unsatisfactory. However,
      endorectal MRI is highly accurate in differentiating localized (stage B) from
      invasive (stage C) cancer.

PMID- 9650428
TI  - Prediction of right ventricular infarction from standard surface ECG in patients
      with inferior myocardial infarction.
AB  - BACKGROUND: Patients with inferior myocardial infarction (MI) have a 45% chance
      of having concurrent right ventricular infarction (RVI); of these, 5-10% suffer
      hemodynamic collapse. Immediate correct diagnosis and appropriate management of
      such patients is vital. ST-segment elevation in the right precordial V4 lead
      (V4R) has a high diagnostic value in identifying RVI, but this determination
      requires additional time and cost. An attempt was made to use a collection of
      patients' standard surface electrocardiograms (ECG) to find any available data to
      detect RVI and to lead to a new way to diagnose RVI. METHODS: Fifty patients
      (males/females, 44/6; mean age, 64.3 +/- 6.9 years) with acute inferior
      myocardial infarction were enrolled in a first group to develop new diagnostic
      criteria for RVI. As a first step, the ST-segment change in every standard
      surface ECG lead was analyzed and compared with corresponding changes in V4R. RVI
      was diagnosed by typical clinical symptoms (chest pain for more than 30 minutes,
      ST elevation > 0.1 mV and enzyme changes) accompanying ST elevation of more than
      0.1 mV in V4R (by Lopez-Sendon criteria) and echocardiographic findings. RVI was
      diagnosed in 24 (48%) patients using ECG. The new criteria were then tested in a
      secondary group of 48 patients (males/females, 43/5; mean age, 65.5 +/- 7.9
      years) with inferior MI. RESULTS: Analysis of these patients found that ST
      depression in lead I and aVL was a specific characteristic of RVI (I + aVL > 0.2
      mV). This criterion was applied to another group of patients with acute inferior
      MI to check the predictive value (sensitivity, 94.7%; specificity, 89.7%;
      positive predictive value, 85.7%; negative predictive value, 96.3%). CONCLUSIONS:
      In patients with evolving inferior MI, standard surface ECG analyzed for this
      criterion could aid clinical recognition of concomitant RVI.

PMID- 9650429
TI  - Endovascular embolization of arteriovenous fistulas of the external carotid
      artery.
AB  - BACKGROUND: External carotid arteriovenous fistulas (AVFs) are rare and most
      hospitals have limited experience with their management. This study was designed
      to evaluate the effectiveness and safety of endovascular embolization of AVFs of
      the external carotid artery under angiographic control. METHODS: A series of 13
      patients with AVFs involving the branches of the external carotid artery, all
      treated with endovascular embolization, were reviewed. There were 10 males and
      three females ranging in age from nine to 46 years, with a mean of 27 years. The
      most frequent presenting symptoms were pulsatile tinnitus, followed by bruit
      and/or thrill, ocular problems, headache and a pulsatile mass in the neck. The
      middle meningeal artery was most often involved, followed by the internal
      maxillary artery and the occipital artery. The AVFs were caused by trauma in 10
      patients and occurred spontaneously in three. N-butyl-2-cyanoacrylate was used to
      embolize the fistula in 11 patients and a detachable balloon was used in two.
      RESULTS: All the patients were cured and no significant complications were
      observed. No recurrence was noted after a clinical follow-up of three months to
      seven years (mean, 37 months). CONCLUSIONS: Endovascular embolization proved to
      be a safe and effective procedure. It should be the treatment of choice for
      repair of external carotid AVFs.

PMID- 9650430
TI  - Analysis of costs borne by families of patients hospitalized for stroke.
AB  - BACKGROUND: Studies focusing on the economic impact of cancer on families have
      emphasized that costs of chronic disease are substantial for patients and their
      families. However, little effort has been devoted to measuring the costs of care
      for families of patients hospitalized with stroke. METHODS: A total of 215 stroke
      patients and their families from four teaching hospitals in the Taipei
      metropolitan area were monitored from the date of the patient's admission to
      hospital until the date of discharge. The value of labor contributed by families
      was estimated by assigning the current monetary market rate of providing health
      aide to the time families spent caring for patients in hospital. Lost earnings of
      patients and families, expenditure for medical care, and expenses for food,
      clothes, adult diapers, transportation and other miscellaneous items were
      determined and summed to arrive at the total family cost of providing care.
      RESULTS: The average cost of care for one family per inpatient day was
      NT$4,358.20. A total of 98.6% of the families incurred labor costs, which
      accounted for about half of family costs for providing care. Hospital bills
      accounted for almost 19% of total family costs. The income loss for families and
      patients accounted for about 25% of total family costs. Expenses for food,
      clothes, transportation, diapers and other illness-related miscellaneous items
      accounted for about 12% of total family costs. Multiple regression analyses
      demonstrated that the number of family members involved in giving care and the
      length of stay are important predictors for the total cost of care. Average total
      family costs per day increased by 24.3% when an additional family member was
      involved in providing care. Total family costs increased 2.5% for each hospital
      day. CONCLUSIONS: If direct and indirect nonmedical costs are not included in the
      total cost calculation for providing hospital care to stroke patients, the
      economic impact of care on families is likely to be underestimated.

PMID- 9650431
TI  - Endoscopic vein harvest for coronary artery bypass surgery.
AB  - BACKGROUND: Despite increased awareness of risk factors, wound complications
      continue to be a problem following coronary artery bypass graft (CABG) surgery. A
      minimally invasive alternative was therefore developed to reduce the risk of
      complications while providing the same benefits as the standard open vein harvest
      procedure. METHODS: Video-assisted endoscopic technique for vein harvest was
      introduced in our medical center in October 1996. The procedure was evaluated and
      compared with the standard open vein harvest procedure. With the endoscopic
      technique, small incisions were made, each about 2-3 cm at the selected access
      sites (groin and above and below the knee). An endopath subcutaneous dissector
      was subsequently inserted along the anterior surface of the saphenous vein with
      the assistance of an endoscope and video monitor. The venous side branches were
      detected and positioned using a vessel dissector. A ligaclip was applied and the
      branches were divided using endopath-scissors. In some cases, the venous branches
      were divided directly using the endopath-scissors. Therefore, the distal and
      proximal ends of the saphenous vein were isolated, ligated and divided. The
      harvested veins were used for CABG. Each patient was evaluated for length of
      surgery, hospital stay and morbidity. RESULTS: From October 1996 through May
      1997, we performed 50 procedures using video-assisted endoscopic vein harvest.
      The results were compared with those from 106 patients who underwent standard
      open vein harvest during the same period. The rate of complications was 2% in the
      endoscopic group compared with 13.2% in the open group (p < 0.05). The average
      hospital stay was 7.2 days in the endoscopic group and 11.5 days in the open
      group (p < 0.05). Twelve weeks after the operation, all of the incisions healed
      with good cosmetic results in the endoscopic group. However, long visible scars
      were found in the patients in the open group. CONCLUSIONS: Endoscopic saphenous
      vein harvest provides a minimally invasive alternative to open vein harvest. It
      provides good cosmetic results without a hypertrophic scar and enables the
      patient to regain early ambulation.

PMID- 9650432
TI  - Malignancy following renal transplantation.
AB  - BACKGROUND: A markedly increased incidence of malignancy in transplant recipients
      is well recognized. However, the incidence and pattern of post-transplantation
      malignancies shows some discrepancy among different reports. The renal transplant
      recipients monitored at Taichung Veterans' General Hospital comprise the largest
      group in Taiwan. An analysis of the characteristics of post-transplant
      malignancies emphasizes the differences from malignancies that occur in the
      Taiwanese general population and those reported in Western countries. METHODS:
      The incidence and characteristics of de novo malignancy in 390 renal transplant
      recipients who underwent renal transplantation between May 1983 and June 1996
      were analyzed. A total of 232 men and 158 women (mean age at transplantation:
      38.5 +/- 10.7 years) were included. The relative risk for developing malignancies
      was calculated based on the sex- and age-matched cancer incidence of reference
      for the Taiwanese population; data from the Cancer Registry Annual Report in
      Taiwan (1989) was obtained for comparison. RESULTS: A total of 25 cancers were
      diagnosed in 24 renal transplant recipients, for an incidence of 6.2%. The
      relative risk of renal malignancy was 13.8-fold higher among transplant
      recipients than in the general population. The impact of gender and age on the
      development of post-transplantation malignancy was not significant. The most
      common types of cancer were transitional cell carcinoma (TCC) of the urinary
      tract (8/25), and hepatoma (8/25), followed by two cases of Kaposi's sarcoma.
      Aside from immunosuppressive agents, the high incidence of hepatoma and TCC may
      be attributed to the high incidence of hepatitis infection and the possible
      carcinogenic effect of abnormal milieu induced by uremia per se. Survival was
      largely dependent on the extent of disease at presentation, and post
      transplantation cancer did not show more aggressive behavior if detected early.
      CONCLUSIONS: The high cumulative incidence of malignancies makes it imperative to
      define an effective safe immunosuppressive regimen to achieve a lower risk of
      malignancies. In the future, the prime approach to treatment of post
      transplantation malignancies should begin with early detection and ensuing
      aggressive treatment to improve the outcome.

PMID- 9650433
TI  - Rupture of rudimentary horn pregnancy: a case report.
AB  - A rare case of rupture of a noncommunicating rudimentary horn pregnancy is
      presented. The pregnancy continued to 16-weeks' gestation, when the rudimentary
      horn ruptured. The patient had signs and symptoms of massive hemoperitoneum. An
      emergency exploratory laparotomy revealed a ruptured rudimentary horn and an
      intact amnionic sac. Prompt excision of the rudimentary horn was performed. The
      relative literature and factors associated with a rudimentary horn pregnancy are
      reviewed and discussed.

PMID- 9650434
TI  - Primary retroperitoneal liposarcoma mimicking ovarian cancer: a case report.
AB  - Primary retroperitoneal liposarcoma is a rare malignancy comprising about only
      0.1% of all cancers. It produces nonspecific symptoms and is often extensive when
      diagnosed. In this report, we present a case of a 68-year-old female patient who
      had a 29-kg retroperitoneal liposarcoma. Her early symptoms--including vague
      digestive disturbances, increasing abdominal girth and an abdominal mass, and
      clinical examinations such as sonography and computed tomography scan led to a
      preoperative diagnosis of ovarian cancer, until surgical and pathologic
      confirmation. Gross, radical resection of the tumor was successfully performed,
      and provided the most effective primary therapeutic approach. Histopathology
      revealed a mixed-type liposarcoma, with metastasis to the appendix. A poor
      prognosis was expected. Postoperative periodic follow-up was started to monitor
      for early detection of recurrence.

PMID- 9650435
TI  - Focal segmental glomerulosclerosis after poststreptococcal glomerulonephritis in
      the elderly: a case report.
AB  - Acute poststreptococcal glomerulonephritis (PSGN) is quite rare in the elderly
      population. It is very difficult to recognize because the initial symptoms are
      similar to those of more common diseases of this age group. Compared with younger
      patients, elderly patients with PSGN tend to have a high incidence of renal
      function impairment and anuria or prolonged oliguria. Recovery from acute PSGN in
      the elderly is less predictable than in children and younger adults, especially
      when associated with severe impairment of renal function. We present the case of
      an elderly patient with PSGN, who had a skin infection of the face and anuria on
      admission. Percutaneous left renal biopsy was performed in the initial
      hospitalization period and in the recovery phase of the disease. Renal function
      recovered within two months. However, increased urinary white blood cell
      sediments with normal serum creatinine concentrations persisted in the successive
      three years of follow-up. Renal biopsy was repeated and showed evidence of focal
      segmental glomerulosclerosis.

PMID- 9650436
TI  - Diagnosis of cerebral toxoplasmosis by a nested polymerase chain reaction: a case
      report.
AB  - A 24-year-old man infected with human immunodeficiency virus type I rapidly
      progressed to acquired immune deficiency syndrome. His clinical picture was
      compatible with a presumptive diagnosis of cerebral toxoplasmosis. Application of
      a nested polymerase chain reaction (PCR) succeeded in detecting Toxoplasma gondii
      DNA in both the venous blood and cerebrospinal fluid specimens. This result
      indicates that PCR is a convenient tool for making a rapid and accurate diagnosis
      of cerebral toxoplasmosis, especially in developing countries.

PMID- 9650437
TI  - Hypnotic susceptibility order effects in waking analgesia.
AB  - This study reexamined Spanos, Hodgins, Stam, and Gwynn's (1984) contention that
      susceptibility testing order effects generated a relationship between waking
      analgesia pain reduction and level of hypnotic responsiveness. Undergraduate
      volunteers with no previous hypnosis experience were randomly assigned to two
      groups. Group 1 (n = 69) first received a cold pressor pain protocol, and then
      was administered the Standford Hypnotic Susceptibility Scale, Form C (SHSS:C).
      Group 2 (n = 69) was administered the SHSS:C prior to the cold pressor pain
      protocol. Our findings do not support Spanos, Hodgins et al.'s contention that
      susceptibility testing order effects generate the often reported relationship
      between waking analgesia and level of hypnotic responsiveness. We found
      significant partial correlation coefficients between the SHSS:C and nonhypnotic
      pain reduction regardless of order of susceptibility testing. Implications
      regarding the adequacy of design-generated expectancies to explain hypnotic
      analgesia phenomena were examined.

PMID- 9650438
TI  - Waterloo-Stanford Group Scale of Hypnotic Susceptibility, Form C: manual and
      response booklet.
AB  - The manual and response booklet for the Waterloo-Stanford Group Scale of Hypnotic
      Susceptibility, Form C (WSGC) is presented. The WSGC is a group adaptation of the
      individually administered Stanford Hypnotic Susceptibility Scale, Form C
      (SHSS:C).

PMID- 9650439
TI  - Experiential scoring for the Waterloo-Stanford Group C scale.
AB  - A scale is presented that assesses subjective experiences associated with the
      test suggestions contained in the Waterloo-Stanford Group C scale (WSGC), a group
      adaptation of the Stanford Hypnotic Susceptibility Scale: Form (SHSS:C). This
      scale, along with the standard behavioral scoring system of the WSGC, was given
      to 926 students at the University of Connecticut. Normative data from this sample
      indicate that the experiential scoring scale is both reliable and valid as a
      measure of suggestibility. It is suggested that it may be useful to supplement
      behavioral scoring with experiential scoring when the WSGC is used.

PMID- 9650440
TI  - Effects on suggestibility of a new method of active-alert hypnosis: alert hand.
AB  - Research has shown that the active-alert method described by Banyai and Hilgard
      (1976) produces a similar increase on suggestibility as relaxation-based
      techniques, but it has some limitations, including the need for a stationary
      bicycle and a certain level of physical fitness. The authors compared that method
      with the new "alert hand" method, which emphasizes activity and alertness, but is
      simpler and less strenuous. In a repeated measures, counterbalanced design (N =
      80), the authors found that (a) the alert hand method produced significantly
      higher objective and subjective suggestibility scores than the active-alert
      technique, and (b) a high percentage (23%) of volunteers discontinued
      participation during the active-alert method but not during the alert hand
      method. The alert hand method extends the benefits of active hypnosis to
      individuals who may have difficulties with the physical demands required by the
      active-alert method, and it seems to enhance suggestibility even more.

PMID- 9650441
TI  - Intentionality during hypnosis: an ironic process analysis.
AB  - Two studies were completed to test whether responding to hypnotic suggestions
      requires intentional effort. Hypnotic suggestions for amnesia were used as an
      analog of thought suppression, and Wegner's model of ironic processing was
      applied to hypnotic responding. In the first study, participants were required to
      maintain suggested amnesia while performing a cancellation task with and without
      a cognitive load. The second study required suppression of thoughts of a favorite
      car, once with "blank-mind" instructions and then with a suggestion for amnesia.
      The results of these studies indicate that dissociated control theory provides
      the best explanation for hypnotic responding in one subset of highly hypnotizable
      participants, whereas more intentional responding provides the best explanation
      for others.

PMID- 9650442
TI  - Multicenter cooperative study group in hematology in Japan: the 10-year history
      and role of the Japan Adult Leukemia Study Group in Japan.
AB  - Leukemia is an uncommon disease. In order to conduct a scientific clinical study,
      a large number of patients is required for reliable statistical analysis, and
      therefore, multicenter cooperative study is indispensable in leukemia. Not only
      in the field of hematology/oncology but also in other fields of clinical
      medicine, well-functioning clinical study groups are still rare in Japan. In this
      review, the reason why the organization of multicenter cooperative study groups
      is difficult in Japan is analyzed. Then the 10-year experience of a self
      supporting and quite successful cooperative study group, the Japan Adult Leukemia
      Study Group, is reviewed. Finally, the next steps for the Group and the way it
      might be successfully led are discussed.

PMID- 9650443
TI  - Usage of activating mutations in the analysis of cytokine signal transduction
      pathways.
AB  - Cytokine signal transduction pathways are highly redundant and complex. The
      analysis of the structure and function of signal transduction molecules was
      conventionally done by using mutated or truncated receptors, dominant negative
      molecules, and knockout mice. These methods are designed to look at the result of
      a subtraction of a part of the whole signal transduction pathway. In contrast,
      analysis using activating mutations of a signal transduction molecule is designed
      to look at the downstream result of one pathway which originated from the
      pertinent molecule. This method is less influenced by other signal transduction
      molecules which may have an overlapping effect on the downstream molecules. By
      combining both the subtraction and activating methods, we can gain more insight
      into the complex interactions between signal transduction molecules. An
      activating mutation of a signal transduction molecule is usually found as an
      oncogene. However, known oncogenes are not always the molecules of interest. In
      this review, several methods to create activating mutations of a target molecule
      are discussed.

PMID- 9650444
TI  - Molecular interaction between factor VII and tissue factor.
AB  - Complex formation between serine protease factor VIIa (VIIa) and tissue factor
      (TF) dramatically enhances the catalytic activity of VIIa, leading to the
      initiation of extrinsic blood coagulation. The recently determined crystal
      structure of the complex formed between VIIa and the extracellular domain of TF
      has revealed in detail the interacting surfaces of the two molecules. Mutational
      and biochemical studies have further identified regions of VIIa and/or those of
      TF essential for the high affinity interaction. These studies indicate that the
      regions extending from the gamma-carboxyglutamic acid domain through the first
      epidermal growth factor-like domain and protease domain of VIIa are involved
      separately in the interaction with the distinct sites of TF. The interaction of
      TF with the protease domain of VIIa apparently induces a conformational
      transition of the VIIa active site. Studies of the chemical modification of VIIa
      provided a model for the mechanism of TF-mediated acceleration of VIIa activity.
      In this model, the protease domain of VIIa exists in equilibrium between minor
      active and dominant zymogen-like inactive conformational states, and preferential
      binding of TF to the active state leads to a shift in equilibrium into the active
      state, thereby accelerating VIIa activity. Overall docking of TF with VIIa in the
      presence of phospholipids further supports a recognition of macromolecular
      substrates, such as factors IX and X. Therefore, single VIIa-TF interaction
      contains several distinct mechanisms for enhancing the coagulant activity of
      VIIa, which may be important for the initiation of coagulation specifically
      mediated by TF. Studies of the interaction between VIIa and TF provide not only a
      detailed understanding of the regulated initiation of blood coagulation but also
      the potential to design novel anticoagulants for the treatment of thrombotic
      diseases.

PMID- 9650445
TI  - Assessment of mitomycin C sensitivity in Fanconi anemia complementation group C
      gene (Fac) knock-out mouse cells.
AB  - Fanconi anemia (FA) is a genetic disorder defined by cellular hypersensitivity to
      DNA cross-linking agents, such as mitomycin C (MMC). MMC causes increased FA cell
      death, chromosome breakage, and accumulation in the G2 phase of the cell cycle.
      Recently, Fanconi anemia complementation group C (fac) gene knock-out mice have
      been developed, and SV40-transformed fibroblasts were established from fac
      homozygous knock-out (-/-), heterozygous (+/-), and wild-type mice (+/+). MMC
      sensitivity of these cell lines was assessed by three methods: colony-formation
      assay in the presence of MMC, chromosome breakage, and cell cycle analysis to
      detect G2 phase arrest. The fac knock-out fibroblasts (-/-) showed a
      significantly higher sensitivity to MMC than did fibroblasts from wild-type (+/+)
      or heterozygous (+/-) mice (three experiments). In addition, we analyzed
      hematopoietic progenitor colony assays of bone marrow cells from fac knock-out (
      /-) and heterozygous (+/-) mice. CFU-E, BFU-E, and CFU-GM colony formation from
      fac nullizygous mouse progenitors was markedly diminished by MMC when compared to
      growth of progenitors from heterozygous mice. These results show that fac knock
      out mouse cells mimic the behavior of human FA-C patient cells in terms of MMC
      hypersensitivity. The fac knock-out mouse may be used to model some aspects of
      human FA and should be useful for understanding the function of the FAC protein.

PMID- 9650446
TI  - PLA2-independent induction of CSF-1 gene expression in growth-arrested
      fibroblasts.
AB  - At the site of a wound or an infection, localized production of colony
      stimulating factor-1 (CSF-1) by resident macrophages is chemotactic for
      circulating monocytes. Several intracellular signaling pathways, including those
      initiated in response to activation of phospholipase A2 (PLA2) have been proposed
      to play a role in the regulation of CSF-1 gene expression. The goal of these
      studies was to determine whether PLA2 is required for the initial increase in CSF
      1 gene expression in serum- or IL-1 alpha-stimulated growth-arrested fibroblasts.
      IL-1 alpha- or serum-stimulation of growth-arrested fibroblasts had no effect on
      PLA2 enzyme activity and inhibitors of cytosolic or Ca(2+)-independent PLA2
      activity had no effect on IL-1 alpha- or serum-mediated increases in CSF-1 mRNA
      levels. High concentrations of the PLA2 inhibitors, 4-bromophenacyl lactone and
      quinacrine, resulted in a generalized decrease in cellular mRNA levels. Our
      results, obtained in fibroblasts, suggest treatment with 4-bromophenacyl lactone
      or quinacrine, instead of inhibiting PLA2 activity specifically, results in a
      generalized depression of cellular mRNA levels. These data demonstrate that the
      initial increase in CSF-1 gene expression in growth-arrested fibroblasts treated
      with serum or IL-1 alpha occurs through a PLA2-independent mechanism.

PMID- 9650447
TI  - Dual action of CD30 antigen: anti-CD30 antibody induced apoptosis and interleukin
      8 secretion in Ki-1 lymphoma cells.
AB  - CD30 is a member of the tumor necrosis factor superfamily. In this study, we
      examined the effect of four anti-CD30 (aCD30) antibodies (Abs) on CD30-positive
      anaplastic large cell lymphoma-derived cell line, Ki-JK. The aCD30 Abs suppressed
      [3H]thymidine (TdR) incorporation. With a TdT mediated dUTP-biotin nick end
      labeling method, apoptosis was detected in Ki-JK cells at day 5 after the
      addition of aCD30 Ab to the culture. Genistein, an inhibitor of protein tyrosine
      kinase, had no effect on aCD30 Ab-induced apoptosis. The aCD30 Ab simultaneously
      induced interleukin-8 (IL-8) secretion in the Ki-JK cells. In culture of the Ki
      JK cells with aCD30 Ab for 5 days, the IL-8 concentration of the cell free
      supernatant increased to 240 +/- 16 pg/ml, though the concentration was < 12.5
      pg/ml without aCD30 Ab. In combination with aCD30 Ab, genistein decreased the
      concentration of IL-8 in day 5 supernatants. Although, doxorubicin and herbimycin
      A suppressed [3H]TdR incorporation and induced apoptosis in the Ki-JK cells, they
      did not induce IL-8 secretion. Only aCD30 Ab-induced apoptosis was accompanied by
      IL-8 secretion. IL-8 mRNA was not detected in the Ki-JK cells by reverse
      transcription-polymerase chain reaction assay. IL-8 mRNA was detected 5 days
      after adding aCD30 Ab to the culture.

PMID- 9650448
TI  - Improved methods of HIV vector mediated gene transfer.
AB  - HIV vectors are capable of targeted gene transfer into CD4+ cells. However,
      extensive testing of HIV vectors in gene therapy applications is hampered by the
      low titer of current HIV vector could be concentrated by approximately 20 times
      by sulfonated cellulose column chromatography. No replication competent
      cytopathic HIV was detected in the concentrated vector preparation. When the
      vector preparation and the target cells were centrifuged at transduction, about a
      five-fold increase in the apparent titer was achieved. Accordingly, by combining
      these two techniques the overall titer was increased by approximately two orders
      of magnitude. Using this high efficiency strategy, we transduced human primary
      lymphocytes that are refractory to transduction with currently available viral
      vectors. Amplification and sequencing of the integration sites showed that HIV
      vectors could stably integrate into the chromosomes of CD4 enriched human
      peripheral blood mononuclear cells. These findings indicate that HIV vectors are
      useful for the development of gene therapy targeting lymphocytes.

PMID- 9650449
TI  - Osteoblastic cells regulate mi gene expression in cultured bone marrow cells.
AB  - The microphthalmia (mi) gene encodes a bHLH-Zip protein and certain mutations in
      this gene are known to result in osteopetrosis. We examined mi gene expression in
      murine bone marrow (BM) cells and calvaria-derived osteoblastic (OB) cells. The
      mi message level in BM cells was three- to four-fold higher than that in OB
      cells. The mi message level in BM cells alone was not enhanced by 1,25(OH)2
      vitamin D3 (vitamin D) which induces TRAP-positive multinucleated cells, but was
      enhanced two-fold by the addition of conditioned medium obtained from cultures of
      OB cells. The mi message levels in BM cells were also enhanced by macrophage
      colony-stimulating factor (M-CSF). The mi message levels in cocultures of BM
      cells and osteoblastic MC3T3-E1 cells, which do not support osteoclastogenesis,
      were similar to those in the cocultures of BM cells and OB cells. Cocultures of
      BM cells with MC3T3-E1 cells did not yield TRAP-positive multinucleated cells,
      but they did maintain osteoclast progenitor cells. These findings suggest that mi
      is expressed in BM cells that may be under the control of OB cells.

PMID- 9650450
TI  - Establishment of novel cell lines derived from two patients with chronic
      myelogenous leukemia in blast crisis; IMS-BC1 and IMS-BC2 which exhibit markedly
      different sensitivity to apoptosis.
AB  - We established two novel cell lines, designated as IMS-BC1 and IMS-BC2, from two
      patients with chronic myelogenous leukemia in blast crisis. The two cell lines
      were positive for CD13 and CD33 and negative for CD34 and HLA-DR by surface
      marker analysis. IMS-BC1 had four Philadelphia (Ph1) chromosomes and a breakpoint
      within the 3'-portion of M-bcr, and IMS-BC2 had five Ph1 chromosomes and two
      breakpoints within the 3'- and 5'-portions of M-bcr. Both cell lines' growth
      activities were moderately suppressed by IFN-alpha. The proliferation of IMS-BC2
      was inhibited by IFN-gamma and apoptosis was induced within 72 h, while IMS-BC1
      was resistant to IFN-gamma. Fibronectin inhibited the proliferation of the two
      cell lines at higher than 10 micrograms/ml, but only IMS-BC2 showed apoptosis.
      Transforming growth factor-beta inhibited the proliferation of IMS-BC2 resulting
      in apoptosis, while it inhibited that of IMS-BC1 moderately but failed to induce
      apoptosis. All-trans retinoic acid (ATRA) inhibited the proliferation of IMS-BC2
      at very low concentration (10(-17) mol/l) and induced apoptosis at doses higher
      than 10(-9) mol/l within 72 h without terminal differentiation, while IMS-BC1 was
      completely resistant to ATRA. The two cell lines showed different responses to
      growth inhibitory cytokines and factors. These cell lines should prove useful in
      the analysis of mechanisms of apoptosis induced by growth inhibitory cytokines
      and factors.

PMID- 9650451
TI  - Establishment and characterization of bone marrow stroma-dependent leukemia cell
      line, HB-1.
AB  - Radiation-induced M361 leukemia bearing mice (M361 mice) show characteristics of
      acute myelogenous leukemia (AML) with granulocytosis. Granulocyte-macrophage
      colony forming unit (CFU-GM) increased in the bone marrow and spleen and high
      activity of colony stimulating factor (CSF) was found in the sera of M361 mice. A
      cell line (HB-1) was established from the spleen cells of M361 mice. Injection of
      HB-1 cells induced a similar leukemic response as M361 in syngeneic mice. HB-1
      cells did not survive in the suspension culture, but proliferated when cultured
      on hemopoietic supportive stromal cells (MS-10). HB-1 cells appear to be strictly
      dependent on the hemopoietic supportive bone marrow stroma, which would provide a
      useful model for the study of cell-cell interactions between hemopoietic cells
      and marrow stromal cells.

PMID- 9650452
TI  - Prolonged secretion of IL-15 in patients with severe forms of acute graft-versus
      host disease after allogeneic bone marrow transplantation in children.
AB  - Graft-versus-host disease (GVHD) is one of the most common and fatal
      complications that follows allogeneic bone marrow transplantation (BMT). Donor
      origin T cells are responsible for the initiation of GVHD. In this report, we
      demonstrate that conditioning regimens for BMT resulted in elevated serum levels
      of interleukin-15 (IL-15), which reached maximum levels within 15 days and
      returned to basal levels within 25 days after allogeneic BMT, in all patients
      examined. Thereafter, circulating IL-15 was detected only in patients with grade
      III or IV acute GVHD with gut involvement. In contrast, IL-2 was not detected at
      any time in these patients. Since IL-15 is able to activate antigen-stimulated T
      cells and natural killer (NK) cells, IL-15 may play an important role in the
      development of severe forms of acute GVHD.

PMID- 9650453
TI  - Elevated expression of differentiation inhibitory factor nm23 mRNA in monoblastic
      crisis of a patient with chronic myelogenous leukemia.
AB  - Differentiation inhibitory factor nm23 gene has been found to be expressed in
      high quantities in acute myelogenous leukemia (AML), especially in acute
      monocytic leukemia (AML-M5) and is suggested as a new prognostic factor in AML
      M5. We report an example of elevated expression of nm23 mRNA in a patient with
      chronic myelogenous leukemia (CML) who developed monoblastic crisis. Relative
      levels of nm23-H1 and -H2 mRNA extracted from the patient's peripheral blood
      mononuclear cells and bone marrow mononuclear cells were measured by quantitative
      reverse transcriptase polymerase chain reaction. The level of nm23-H1 mRNA in CML
      cells at the chronic phase was as high as that in bone marrow cells from healthy
      volunteers. The mRNA level of nm23-H2 was slightly below the normal level. At
      blastic crisis, however, expression of both nm23-H1 and -H2 mRNA was elevated to
      about three to nine times of that at the chronic phase. Proliferated blastic
      cells were positive for non-specific esterase, and the serum lysozyme level was
      elevated and diagnosed as monoblastic crisis. The patient received combined
      chemotherapy but response was partial. These findings are compatible with our
      previous report that nm23 gene is overexpressed in monocytic leukemia.

PMID- 9650454
TI  - Development of Epstein-Barr virus-associated B cell lymphoma after intensive
      treatment of patients with angioimmunoblastic lymphadenopathy with
      dysproteinemia.
AB  - Evolution of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) into
      aggressive B cell lymphoma is thought to be a rare event and the cause of this
      transformation has not been fully elucidated. We describe two patients with AILD
      that progressed to aggressive large-cell lymphoma with a B cell phenotype. At
      presentation, the lymph nodes of both patients showed the typical features of
      AILD by hematoxylin-eosin staining. Immunohistochemical staining with monoclonal
      antibodies revealed positive staining of atypical cells with UCHL-1 and negative
      staining with L-26. In situ hybridization of EBV RNA showed rare positive cells
      in one patient and was negative in the other patient. At relapse, both patients
      showed systemic lymph nodes swelling, which is characteristic of diffuse large
      immunoblastic lymphoma. Single-cell analysis with monoclonal antibodies and
      immunohistochemical staining showed the monoclonal proliferation of B cells.
      Southern blot analysis of the lymph nodes showed a rearrangement in both patients
      of the Ig heavy chain gene and germ line configuration of the T cell receptor
      beta chain gene. Southern blot analysis using the EBV terminal repeat region
      probe detected clonal proliferation of EBV in the lymph nodes of both patients.
      In situ hybridization studies identified considerable EBV mRNA in both patients.
      These observations suggest that EBV proliferation plays an important role in the
      development of B cell lymphoma that arises from AILD. We suggest that infection
      or reactivation of EBV may occur in some patients with AILD, probably due to
      their immunodeficient state, and that this infection or reactivation is directly
      involved in the development of B cell lymphoma.

PMID- 9650456
TI  - [Physical and chemical properties of vanadium and its compounds].
AB  - Vanadium is present in the earth crust mainly in the heavy oils, carbons and
      bituminous materials, where is associated with the heavy fractions. Many live
      beings have vanadium in their tissues. Their industrial applications are
      fundamentally based in the physical and chemical properties. From the
      environmental point of view the vanadium emissions to the atmosphere are produced
      in areas around siderurgical industries, oil refineries and cities that use
      fossil fuels for heating. The pollution process in these areas is associated
      partially with the presence of vanadium compounds, as is the case in the eastern
      coast of the lake of Maracaibo, Venezuela. Some clinical-epidemiological
      researches report a high incidence of congenital malformations at the Central
      Nervous System level, and this has been associated with the intense oil
      activities of the region. The high incidence of the Central Nervous System
      congenital malformations could be associated with the vanadium compounds present
      in the eastern coast of the lake of Maracaibo; here is the interest in the
      physical and chemical properties knowledge of vanadium and their compounds.

PMID- 9650457
TI  - [Role of vanadium in metabolism].
AB  - The trace element vanadium, has been studied during the past few years, however
      is unknown its cellular actions. This paper intends to give a review of the
      different vanadium routes, its absorption, distribution, metabolism and
      biotransformation, mainly because vanadium use has increased in the petroleum and
      steel industries affecting their workers for its toxic effects.

PMID- 9650458
TI  - [Determination of vanadium concentration in foods produced on the Eastern Coast
      of Lake Maracaibo].
AB  - In the northeastern coast of Lake Maracaibo it has been reported some years ago a
      high incidence of congenital malformations of the Central Nervous Systems (Neural
      Tube Defects Type). This epidemiological problem is present in other countries
      too (Ireland and New Zealand) and has been associated with oil activities. In
      fact, some experimental works inform about the vanadium compounds cellular toxic
      effects mainly in the Central Nervous System of mammals. The main goal of this
      work is to measure the vanadium content in foods produced in the northeastern
      coast of Lake Maracaibo. Lagunillas, Valmore Rodriguez, and Baralt were the
      districts selected for the work. The digestion of the samples achieved by the
      methodology reported by Myron et al., with Graphite Furnace Atomic Absorption.
      The amounts of vanadium in the different foods analized were higher than the
      controls in the bibliographic reports. At this moment, there is not definitive
      proofs that vanadium compounds are the etiological agents of the Neural Tube
      Defects, but, these compounds are presents in foods produced in the northeastern
      coast of Lake Maracaibo.

PMID- 9650459
TI  - [Genotoxic effects of vanadium compounds].
AB  - Vanadium is a metal member of the periodic table VB group, with atomic weight
      59.95 and atomic number 23 and it has some oxidizing states from -1 to +5.
      Vanadium has many industrial uses and its contribution with environmental
      contamination is growing every day. In the last 10 years research about the
      vanadium effects on living beings, has been increasing substantially, due to its
      presence in the environment from different sources. Interest for vanadium and
      their compounds is because its toxic effects and uses in some biomedical areas:
      such as antineoplastic, cholesterol and glucose level blood, diuretic, oxygen
      haemoglobin affinity. Vanadium toxic effects are so due to the fact of its
      property of inhibiting many enzymatic systems. Vanadate and vanadyl ions make
      chemical complexes exhibiting the property of inhibiting or increasing the
      activity of the enzymes participating in the DNA and RNA synthesis. They also
      induce mutagenic and genotoxic effects. Biochemical assays show cytotoxic
      effects, increase in the cellular differentiation, gene expression alterations
      and other biochemical and metabolic alterations. Research has been done with in
      vitro systems, but few with laboratory animals. It is necessary to carry out more
      work in the field of genetic toxicology with vanadium compounds. This type of
      compounds may be considered mutagenic and genotoxic, with cytotoxic and
      aneuploidogenous effects.

PMID- 9650460
TI  - [Teratogenic effect of ammonium metavanadate in Swiss albino mice].
AB  - Far as it is known to us, there is only one report in the medical literature
      dealing with the teratogenous effect of vanadium on neural structures (1): while
      trying to experimentally induce anencephaly in the offsprings of swiss-albino
      mice through the administration of ammonium metavanadate via drinking water,
      during different stages of their lives; a neural tube defect consisting of
      arrhinencephaly was obtained; various degrees of hypoplasia or aplasia of both
      the olfactory bulbs and tracts were evidenced, as well as congenital lesions of
      variable intensity in other rhinencephalic structures. The probable mechanisms
      through which vanadium exercises its neural teratogenous effect are analyzed.

PMID- 9650461
TI  - [Teratogenic effects of ammonium metavanadate on the CNS of the offspring of
      albino rats. A histological and histochemical study].
AB  - The vanadium is a metallic oligoelement present in the majority of tissues. Its
      abnormal biological disposal environment can be related with its possible
      teratogenicity and alteration in the contents of glycosaminoglycans acids (GAGs),
      which participate in the morphological processes and the maturation of Central
      Nervous System (CNS). The proposal of the project is to analyze the teratogenic
      effect of ammonium metavanadate (AMV) and its action on the GAGs in the CNS of
      the litter of albino rats. The ammonium metavanadate was diluted in distilled
      water in concentration of 100 and 200 ppm, drunk by the rats since their birth
      and/or weaning to adult age, except during the matching and gestation. The
      animals control drunk water without this metal. The litter were analyzed to
      detect possible congenital malformations, then CNS were removed of descendents
      and were processed by light microscope, cuts of 6 u were stained with H/E; Alcian
      Blue pH 3.5 and 5.6, this last one concentrations of C12Mg from 0.05 M to until
      1.0 M. Previously parallels sections were treated with testicular hyaluronidase.
      The macroscopic analysis of the new born rats that came from rats that received
      AMV in concentrations 100 and 200 ppm, resulted in congenital anomalies like
      unilateral hypoplasia of olfactory bulbs and cerebral hemisphere. The microscopic
      analysis revealed changes in the layers patron of olfactory bulbs and an
      increased of alcianophilia in the pH 5.6 to 0.2 M MgC12, in the extracellular
      matrix of CNS of rats descendents treated with AMV to the dose 200 ppm, sensibles
      to the testicular hyaluronidase, corresponding to hyaluronic acid (HA) and
      chondroitin 4 and/or 6 sulphate (C4S or C6S) of low grade of sulphation. These
      results suggest that the AMV given to albino rats has a teratogenic result when
      it is used before the gestation and for long periods of animals life that alter
      the of GAGs of CNS contents during the development.

PMID- 9650462
TI  - [Toxic effects of ammonium metavanadate on the growth and number of the offspring
      of Swiss albino mice].
AB  - The present research show, an statistical study of the effects of ammonium
      metavanadate (AMV) on size, weight and number of offsprings of 56 albino swiss
      mice (male and female) was carried out. These mice ingested AMV in concentration
      of 100 and 200 ppm "ad libitum" since birth, continuing throughout breasting
      until mating. The control group received water free from the metal. The
      statistical results, obtained by the Duncan and Tukey method, were the following:
      a significant drop in body size in 200 ppm concentration of AMV, and in tail size
      in a concentrations of 100 and 200 ppm. A significant increase was observed in
      the number of the offsprings on the groups treated with AMV on a concentration of
      200 ppm with respect to the control group.

PMID- 9650463
TI  - [Changes in female reproduction induced by ammonium metavanadate in Swiss albino
      mice].
AB  - Female reproduction alterations induced by vanadium salts, taken in periods no
      related with mating/gestation, correlated with histological alterations has not
      been reported. Vanadium is a metal from VB group of periodical table, and it has
      been detected in high concentrations in heavy petroleum produced in this region
      of our country, there have not had investigations about vanadium effect on
      species reproduction. In this work 100 and 200 ppm doses of ammonium vanadate
      (A.M.V.) prepared with demineralized water were administered orally to swiss
      albino mice in different periods. The administration of vanadium salt was
      suspended before mating. Pregnant mice were allowed to deliver and a statistical
      analysis were performed to pregnancy percent and pups means. Non pregnant mice
      were killed after 21 days of mating. Uterus and ovaries were weight, luteal
      bodies were counted and histological samples of ovaries were prepared. The
      results shown a non significative increase of pregnancy (p < 1) in mice exposed
      from weaning to adult, for animals exposed to maximum concentrations 200 ppm a
      significative reduction of pregnancy (p = 0.00001), to mean pups were detected (z
      = 0.68), and number of luteal bodies (s = 3.3 +/- 0.5). The microscopic
      observation shown polycystic ovary, atresic follicular increasing, follicle in
      mature stage and luteal bodies; hard decreasing; hard depletion was observed in
      thecoluteic cells of luteal bodies. A.M.V. modify reproduction even though if
      exposition have been made in period before mating and pregnancy. As doses and
      exposition periods increase detrimental effects induces alteration in the
      follicular phase and luteal of ovarian cycle. Epidemiological and genetic studies
      are recommended in regions where vanadium concentrations are high, and the
      drinking water and foods are contaminated with this metal, in order to know how
      it affect human reproduction.

PMID- 9650464
TI  - [Genotoxic effects of vanadyl sulfate in Drosophila melanogaster].
AB  - This study presents the analysis of chemically induced somatic mutation in
      Drosophila larvae assayed later as single light (LS) mosaic spots in the adult
      eye. The larvae were treated with Vanadyl sulphate (VOSO4), the highest exposure
      was 10.0, 8.0, 6.0 and 4.0 mM which was the acutely lethal concentration, while
      than lowest exposure of 2.5, 2.0 and 1.0 mM, cause reproductive effects and
      genotoxic activity, compared to the control. Previous to the realization of the
      mutagenicity assay was determined the lethal toxicity of the compound undertest
      since the concentration-mortality relationship is a useful indicator of the
      biological activity of Vanadium. The toxic effect in fly adult was to compare any
      differences in the sensitivity of males (white) and female (oregon), observing
      the higher sensitivity of the males. The date presented with tests SMART and
      their statistical evaluation lead to the following conclusions. To test the two
      hypotheses was propose to apply the conditional binomial test (Kastenbaum and
      Bowman, 1970) or the X2 test for proportions (K. Pearson criterion). Each
      hypothesis was tested at the 5% significance level. In conclusion the Vanadyl
      Sulphate produce aberrant red sector in w+/w, it is not correlated with the
      capacity of an agent to induce chromosomal damage and mitotic recombination, but
      rather seems positively correlated with its weak capacity to produce points
      mutations.

PMID- 9650465
TI  - Fifteen years' experience with gastric partitioning for obesity treatment.
AB  - Most reports derived from experiences in Western countries indicate that surgery
      offers the best hope for morbidly obese patients. We report our experience with
      gastric partitioning in 63 Chinese patients (17 men and 46 women) aged 14 to 42
      years, whose preoperative excess weights ranged from 62.3% to 166.7% above their
      ideal body weight. Transverse stapling was performed in 30 patients treated
      before April 1983, while vertical stapling gastric partitioning with a window and
      a Marlex band to encircle the outlet tract was done in 33 patients after that. No
      patient died, but one had leakage at the anastomosis. Success was defined as a
      return to within 50% of the ideal body weight. Vertical-windowed gastric
      partitioning with a Marlex-banded outlet resulted in a significantly higher
      success rate than transverse stapling--70% vs 37%. Our experience suggests that
      vertical-windowed gastric partitioning with a Marlex-banded outlet is a safe and
      effective surgical treatment for morbidly obese Chinese people.

PMID- 9650466
TI  - Urinary endothelin-1 in children with acute renal failure of tubular origin.
AB  - To understand the changes of urinary endothelin-1 (ET-1) concentrations in acute
      renal failure (ARF) and to investigate the origin of human urinary ET-1, we
      studied urinary ET-1 excretion in 70 normal children and 12 children with ARF
      caused by tubular dysfunction. Urinary ET-1 excretion was expressed as a ratio of
      urinary ET-1 to urinary creatinine (ET-1/Cr). Among healthy children, the highest
      urinary ET-1/Cr values were found during infancy. In patients with ARF, there was
      a positive correlation between urinary ET-1/Cr values and daily total urinary ET
      1 (r = 0.42, n = 26, p < 0.05). Plasma ET-1 concentrations were elevated in
      children with ARF during the period of peak serum creatinine concentration.
      During the course of ARF, the lowest urinary ET-1/Cr value occurred during the
      period of peak serum creatinine, whereas the plasma ET-1 concentration declined
      after the peak. These results provide insight into the developmental changes of
      urinary ET-1 values in normal children, and illustrate the pattern of changes in
      plasma and urinary ET-1 concentrations during the course of ARF in children. The
      results suggest that renal production, rather than clearance from the circulation
      by glomerular filtration, may be the source of urinary ET-1.

PMID- 9650467
TI  - Liquid ventilation for treatment of meconium aspiration syndrome in a piglet
      model.
AB  - We tested the hypothesis that liquid ventilation (LV) with perfluorocarbon (PFC)
      can remove aspirated meconium and improve lung function in experimental meconium
      aspiration syndrome (MAS). PFC (FC-77) was used as the medium in LV. Sixteen
      piglets were divided into control and LV groups (8 animals/group). All animals
      received slurry meconium (20% in normal saline) via endotracheal instillation at
      baseline. Thirty minutes later, the LV group received 15 cycles of LV. Pulmonary
      mechanics, arterial blood gases, and hemodynamic values were recorded at
      baseline, and 30, 60, 120, 180, and 240 minutes after meconium instillation.
      Chest radiographs and lung sections were taken and scored at the end of the
      study. The percentage of meconium cleared by LV was calculated as the ratio of
      the dry weight of washings to that of meconium instilled, multiplied by 100. The
      procedure was tolerated well by the animals. LV cleared 25% +/- 7% of the
      instilled meconium. Tidal volume (9.5 +/- 2.0 vs 7.1 +/- 0.8 mL/kg, p = 0.012),
      respiratory system compliance (2.32 +/- 0.60 vs 1.60 +/- 0.24 mL/cmH2O, p =
      0.01), PaO2 (65 +/- 7 torr vs 55 +/- 6 torr, p = 0.0067), and arterial to
      alveolar oxygen ratio (0.14 +/- 0.01 vs 0.12 +/- 0.01, p = 0.0077) were improved
      in the LV group at 60 minutes after meconium instillation compared with those of
      the control group. The scores of exudative debris (1.7 +/- 0.3 vs 2.1 +/- 0.2)
      and visible meconium (1.4 +/- 0.5 vs 2.1 +/- 0.5) were significantly lower in the
      LV group. In conclusion, short-term L.V with FC-77 can partially remove aspirated
      meconium from the lungs and improve pulmonary function transiently.

PMID- 9650468
TI  - Dideoxy fingerprinting for rapid screening of rpoB gene mutations in clinical
      isolates of Mycobacterium tuberculosis.
AB  - Rifampin is a key component of therapeutic regimens for tuberculosis control, and
      a marker for multidrug resistance of Mycobacterium tuberculosis. Mutations
      responsible for conferring rifampin resistance in M. tuberculosis are known to
      occur in a 69-bp region of the rpoB gene. In this study, we assessed the accuracy
      of dideoxy fingerprinting (ddF), a hybrid technique employing elements of dideoxy
      sequencing and single-strand polymorphism analysis, for rapid screening of
      rifampin resistance in clinical isolates of M. tuberculosis. This technique was
      used to analyze 72 M. tuberculosis isolates. The results were compared with those
      of automated dideoxy sequencing and the antibiotic resistance profile (determined
      with the BACTEC system). Of the 72 isolates, 50 were rifampin resistant. The ddF
      findings were completely consistent with those of dideoxy sequencing in all
      isolates. In 68 (94%) isolates, the ddF findings were consistent with the
      rifampin resistance status determined with the BACTEC system; all four isolates
      with inconsistent results had no mutation in the 69-bp region, but were resistant
      to rifampin. Our findings suggest that ddF accurately detects mutations in the
      rifampin resistance-associated 69-bp region of the rpoB gene in clinical isolates
      of M. tuberculosis, and may be a valuable screening tool for rifampin resistance.

PMID- 9650469
TI  - Bacteremia in patients with hematologic malignancies.
AB  - The decision regarding the appropriate empirical antibiotic therapy for
      bacteremia in patients with hematologic malignancies must be individualized in
      each institution, by taking into account variations in the patterns of microbial
      isolates and their resistance profiles. Microbial isolates and antibiotic
      resistance patterns must be taken into account at each hospital. A shift from
      bacteremia due to infections caused by predominantly gram-negative organisms to
      predominantly gram-positive organisms in patients with hematologic malignancies
      has been noted in reports from other countries. We investigated bacterial
      isolates and their antibiotic sensitivities in patients with hematologic
      malignancies in the Veterans General Hospital-Taipei. A total of 185 episodes of
      bacteremia in 140 patients with hematologic malignancies were recorded during the
      period from 1995 to 1996. Unlike foreign reports, our investigation shows that
      gram-negative organisms still predominate, accounting for 72.7% of isolates,
      followed by gram-positive organisms, accounting for 26.3% of isolates, and
      anaerobes, accounting for 1% of isolates. Escherichia coli was the most commonly
      isolated organism, accounting for 23.9% of isolates, followed by Klebsiella
      pneumoniae (18.5%), Pseudomonas aeruginosa (12.2%), Enterobacter cloacae (7.3%),
      and methicillin-resistant Staphylococcus aureus (7.3%). A high mortality rate was
      observed in gram-negative bacteremia: 31% for E. coli, 26% for K. pneumoniae, 24%
      for P. aeruginosa, and 33% for E. cloacae. If methicillin-resistant S. aureus
      bacteremia occurred, mortality was high (47%). The antibiotic sensitivity
      profiles of the four most common gram-negative isolates (E. coli, K. pneumoniae,
      P. aeruginosa, and E. cloacae) indicated that, in our hospital, amikacin with
      either cefoperazone, ceftazidime, ciprofloxacin, or imipenem, would be an ideal
      combination for empirical therapy for bacteremia in patients with hematologic
      malignancies.

PMID- 9650470
TI  - Hybrid total knee arthroplasty: a 3- to 6-year outcome analysis.
AB  - We retrospectively analyzed the outcomes of hybrid total knee arthroplasty (TKA)
      with Miller Galante I (MG I) prostheses in 113 consecutive patients (140 knees).
      The mean follow-up period was 4.8 years (range 3.2-6.6). There were 135 cases of
      osteoarthritis and five of rheumatoid arthritis. The average age of patients at
      the time of surgery was 62.6 years. The Hospital for Special Surgery knee score
      along with radiographs were used to evaluate preoperative and postoperative knee
      status, and the Cybex isokinetic test was used to assess muscle strength at the
      final follow-up. The average knee score improved from 64 points preoperatively to
      90 points postoperatively (p < 0.05). The mean motion are of the knee improved
      from 108 degrees preoperatively to 116 degrees at the final evaluation. A total
      of 122 knees were pain free on walking and 130 knees were completely pain free at
      rest. A total of 134 knees achieved good to excellent clinical results. The
      radiographic results showed that the mechanical axis of the lower extremity was
      realigned from a mean of 12 degrees varus preoperatively to a mean of 1 degree
      varus postoperatively. No obvious radiolucent zones were found on the lateral
      view of the femoral components in 60.7% of the knees, or on the anteroposterior
      or lateral views around the tibial components in 49.3% and 82.9% of knees,
      respectively. The Cybex isokinetic test at the final follow-up examination
      revealed that the hamstring/quadriceps peak torque ratio was 0.8 at a speed of 60
      degrees per second and 0.96 at 180 degrees per second, indicating that quadriceps
      muscle strength did not recover to within the range of healthy subjects. There
      were 23 (16.4%) complications, including polyethylene wear of patellar components
      (14), patellofemoral maltracking (4), septic loosening (2), aseptic loosening
      (2), and superficial infection (1). Revision surgery improved the functional
      outcomes in all of these knees. Based on our experience, we do not recommend the
      use of the MG I prosthesis in total knee arthroplasty (TKA) because of the high
      rate of patellar complications. Strengthening of the quadriceps must be
      emphasized in postoperative rehabilitation. Hybrid fixation might be a useful
      alternative fixation mode in TKA procedures.

PMID- 9650471
TI  - Evolution of dilated cardiomyopathy from hypertrophic obstructive cardiomyopathy
      in a child.
AB  - Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are two
      different diseases and have distinct etiologies. HCM is rare in children and
      rarely progresses to DCM. We report a 5-year-old Taiwanese girl with a definite
      diagnosis of hypertrophic obstructive cardiomyopathy. The diagnosis was based on
      echocardiograms, cardiac catheterization, and endomyocardial biopsy. However, the
      clinical features progressed to a picture of nonobstructive HCM at age 9, and the
      patient developed dilated poorly contractile ventricles with intractable
      congestive heart failure at age 10. She died from ventricular tachycardia at age
      13. This report emphasizes the importance of periodic reevaluation for children
      with HCM.

PMID- 9650472
TI  - Response of Epstein-Barr virus-associated Ki-1+ anaplastic large cell lymphoma to
      13-cis retinoic acid and interferon alpha.
AB  - The response of peripheral T-cell lymphoma to 13-cis retinoic acid (13-cis-RA)
      has been well established, especially in Ki-1+ anaplastic large cell lymphoma
      (ALCL) confined to the skin. Here, we report the use of 13-cis-RA in combination
      with interferon alpha in a patient with refractory ALCL. The patient, an 18-year
      old man, suffered from retroperitoneal, hepatic, and splenic ALCL. Reactive
      hemophagocytic syndrome also developed. Active Epstein-Barr virus infection was
      demonstrated by serologic tests and in situ hybridization of Epstein-Barr virus
      early RNA-1. Although high-dose intravenous immunoglobulin (IgG), etoposide, and
      steroids were administered, only chemotherapy (methotrexate, bleomycin,
      doxorubicin, cyclophosphamide, vincristine, and dexamethasone) successfully
      controlled the progress of hemophagocytosis. However, the retroperitoneal mass
      and splenic tumor did not show a satisfactory response to three cycles of
      chemotherapy. Hence, interferon 4.5 MU/m2 every other day with 13-cis-RA 1
      mg/kg/day was instituted. Abdominal computed tomogram after 58 days of treatment
      revealed that the tumor had significantly reduced in size. Bone marrow biopsy
      demonstrated alleviation of hemophagocytosis as well. However, lymphoma cells had
      begun to infiltrate the bone marrow. Our findings suggest that 13-cis-RA and
      interferon alpha may be partially effective in treating ALCL.

PMID- 9650473
TI  - Conjunctivitis caused by Thelazia callipaeda infestation in a woman.
AB  - Thelazia is a nematode (Spirurida) that can parasitize the mammalian conjunctival
      sac. This is the first reported case of ocular. Thelazia callipaeda infestation
      in Taiwan. A 41-year-old woman experienced swelling, itching sensation and
      occasional blurred vision of the right eye 2 weeks after a small group of flies
      swarmed her eye while she was hiking. Her symptoms were first misdiagnosed as
      allergic conjunctivitis at a local medical clinic. During her first visit to our
      outpatient department, five white thread-like living worms were discovered on the
      superior and inferior fornices. The worms were cream-colored, slender and
      approximately 1 cm in length. Follicular and papillary conjunctivitis was noted
      in her right eye. After removing the worms, the symptoms resolved and no other
      worms were found in the following 2 months. This case is a remainder to
      physicians that parasitic infestation should be included in the differential
      diagnoses of ocular itching, conjunctivities, and blurred vision after insect
      contact.

PMID- 9650474
TI  - Regional nerve block for total knee arthroplasty.
AB  - Femoral and sciatic nerve blocks have been used occasionally for unilateral total
      knee arthroplasty (TKA). In order to evaluate the effectiveness of this
      technique, combined femoral 3-in-1 and sciatic nerve blocks were performed in 20
      cases of TKA, by the same surgeon. This surgeon also performed unilateral TKA
      under spinal anesthesia in another 20 cases. The anesthetic effectiveness of the
      two types of anesthesia was compared in terms of the time needed to complete the
      surgery, amount of intraoperative blood loss, and time interval until the first
      dose of analgesic. The results showed that the two types of anesthesia had
      comparable anesthetic effects. Ten of the 20 patients who had spinal anesthesia
      complained of postoperative urinary retention, while none of those who had nerve
      block had this complaint. Neither group experienced postpunctural headache,
      neurovascular damage, or drug-over-dose toxicity. We conclude that combined
      femoral 3-in-1 and sciatic nerve block is an effective anesthetic alternative for
      unilateral TKA.

PMID- 9650475
TI  - Adrenal extramedullary hematopoietic tumor in a patient with beta-thalassemia.
AB  - We report a case of adrenal extramedullary hematopoiesis in a 27-year-old woman
      with beta-thalassemia. She underwent cholecystectomy for gallstones and
      splenectomy for splenomegaly at the age of 20 years. In January 1996, she was
      admitted to our hospital because of a palpable nontender mass in the right
      subcostal area. Ultrasound, computed tomography, and magnetic resonance imaging
      disclosed a right suprarenal mass 7.5 x 5.8 cm in size. Surgical exploration and
      biopsy confirmed the diagnosis of extramedullary hematopoietic (EMH) tumor. The
      tumor was left in situ. Subsequent follow-up showed no increase in the size of
      the tumor and no progression of anemia. The patient remained asymptomatic, and no
      additional EMH tumor developed. Surgery or radiotherapy should be performed only
      when EMH tumors cause symptoms, such as during spinal cord compression. Adrenal
      EMH tumors should be considered in thalassemia patients with an adrenal mass, to
      avoid unnecessary surgical procedures.

PMID- 9650476
TI  - [Surgical treatment of war injuries of the veins].
AB  - Between April 1991 and December 1995, 118 patients were treated for wartime
      venous injuries. There were 108 (91.5%) venous injuries combined with arterial
      ones, and 52 (49%) with bone fractures. A total of 85 (72%) venous repairs were
      done and 33 (27.9%) were treated by ligation. Arteriovenous fistulas were found
      in 20 (16.9%) venous injuries. Venous injuries were associated with 10 (62.5%)
      amputations and 5 (45.4%) deaths. In the early postoperative period the authors
      found 15 (17.6%) thromboses of venous reconstructions.

PMID- 9650477
TI  - [Prognostic value of determination of the presence and histologic grade of the
      intraductal component in invasive ductal carcinoma of the breast after
      conservative treatment].
AB  - In recent years, breast-conserving therapy and radiation therapy have become an
      important treatment option for patients with stage I and II invasive breast
      cancer. The results of long-term retrospective studies have demonstrated that
      this treatment can provide a high level of local tumor control with satisfactory
      cosmetic results. Numerous studies have shown that the presence of extensive
      intraductal component (prominent intraductal carcinoma) is highly associated with
      subsequent local recurrence. In this article we have stressed the value of the
      determination of the presence and the histologic grade of prominent intraductal
      component of invasive ductal breast carcinoma in the determination of the extent
      of surgery. We also point out the possibility of determination of prominent DCIS
      on frozen sections.

PMID- 9650478
TI  - [Acute respiratory infection in general clinical practice].
AB  - Due to high frequency, certain risk of related complications, absenteeism, direct
      and indirect costs related to them, acute respiratory infections represent a
      significant health problem. The aim of the paper is to examine the frequency and
      characteristics of acute respiratory infections, as well as the characteristics
      of patients with these infections among the population in care of general
      practitioners/family physicians. In 11 teaching general practices in Zagreb, data
      were collected from medical records on patients and acute respiratory infections
      which the patients developed over the period from October 1, 1994 to September
      30, 1995. For statistical data processing description, distribution analysis and
      chi-square test were used. Out of 17,888 patients in care of general
      practitioners involved in the study, acute respiratory infections were noticed in
      4,114 (22.9%) patients ranging in age from newborn to 97 years out of which 1,473
      (35.8%) were males and 2,641 (64.2%) were females. A total of 5,892 acute
      respiratory infections were observed, in average 1.43 infections per patient, for
      which the patients visited their general practitioners 11,610 times (1.97 visits
      per infection). Most of the patients 2,958 (71.9%) attended their general
      practitioners because of one acute respiratory infection. The initial diagnosis
      of acute upper respiratory tract infection was registered in 4,601 (78.1%)
      infections, and final diagnosis in 4,475 (75.9%) infections. The most frequent
      diagnoses included: pharyngitis and tonsillitis (including streptococcal
      pharyngitis and tonsillitis), nasopharyngitis, sinusitis and bronchitis. In 4,874
      (82.7%) cases, general practitioners based their diagnosis on patient history and
      clinical examination. Antibiotics were prescribed in 3,892 (66.1%) cases. Out of
      42 (1.2%) patients treated in hospital, seven patients were admitted for
      tuberculosis and two for bronchi cancer detected during the acute respiratory
      infection. Follow-up was reported in 3,644 (60.3%) cases, and sick leave in 1,236
      (31%) cases. The results of this study have shown significantly higher frequency
      of acute respiratory infections in the morbidity in outpatient health care, and
      also that management of patients with these diseases is mainly the responsibility
      of general practitioners. In order to improve professional competence of general
      practitioner/family physician and quality of work in the management of patients
      with acute respiratory infections in general practice/family medicine, it is
      necessary to continuously improve the knowledge on all characteristics of the
      management of patient with these diseases in general practice, as well as to make
      a critical assessment of the existing practice.

PMID- 9650479
TI  - [Comparison of the convergence:accommodation ratio in amblyopes treated with
      various pleoptic methods].
AB  - C:A ratios were tested in 50 amblyopes healed by methods of penalization and in
      50 amblyopes healed by classic pleoptic methods. C:A ratios were same for both
      groups of subjects, so both methods of treatment can be applied in this sense.

PMID- 9650480
TI  - [First degree atrioventricular block caused by a calcified tumor of the
      atrioventricular septum].
AB  - First degree atrioventricular block occurred in a 69-year-old patient with a
      calcified atrioventricular septum tumour. The patient suffered several episodes
      of syncope and the only abnormality found in the routine clinical work-up was a
      remarkable first degree atrioventricular block. The echocardiogram, computed
      tomography (CT) and the magnetic resonance imaging (MRI) procedure showed a
      calcified tumour in the posterior part of the left ventricle, between the left
      atrium and left ventricle, just beneath the aortic root spreading to the
      interventricular septum. It was suggested that the first degree atrioventricular
      block was caused by the tumour. The symptoms were relieved by implantation of
      permanent cardiac pacemaker.

PMID- 9650481
TI  - [X-linked adrenoleukodystrophy--2 case reports].
AB  - Cases of a ten-year-old boy with childhood cerebral adrenoleukodystrophy (ALD)
      and a 22-year-old youngster with adrenomyeloneuropathy (AMN) are reported. ALD is
      an inherited, X-linked perixisomal disorder associated with the accumulation of
      very long chain fatty acids (VLCFA). Neurological symptoms occur due to
      progressive demyelination and destruction of cerebral white matter and primary
      adrenal insufficiency. The boy with ALD manifested neurological signs (impaired
      spatial orientation, visual disturbances, poor handwriting, seizures). Latent
      primary adrenal insufficiency was established, and successfully treated by gluco-
      and mineralocorticoids. Lorenzo's oil (mixture of
      glyceroltrioleate:glyceroltrierucate 4:1) treatment significantly reduced
      elevated concentrations of VLCFA, but in spite of that, neurological symptoms
      progressed and the boy died a year after the initial clinical presentation of the
      disease. The boy with AMN revealed primary adrenal insufficiency at the age of 15
      years. AMN was suspected when hair and eyebrows loss occurred and the diagnosis
      was established due to elevated VLCFA levels in the serum at the age of 22 years.
      On examination no neurologic signs of the disease could be detected. Adrenal
      insufficiency is well controlled by gluco- and mineralocorticoids. In addition to
      the previously described two women who were symptomatic heterozygotes we now also
      report on two patients with ALD and AMN. The patients reported are the first four
      with this peroxisomal disorder described in Croatia so far. Probably a great
      number of such patients remains unrecognised. Therefore, it is necessary to
      measure the serum VLCFA levels in males with primary adrenal insufficiency, and
      in those with signs of progressive central demyelination and destruction of
      cerebral white matter accompanied by neurological symptoms of unknown etiology.

PMID- 9650482
TI  - [Injuries in the etiopathogenesis of multiple sclerosis].
AB  - An injury might derange the protective function of the blood-brain barrier, and
      thus it represents one of the possible pathogenetic factors in the demyelination
      of the neural axis. However, the effect of injury on the occurrence or
      deterioration of multiple sclerosis is still controversial. According to most
      authors, the importance of injury in individual cases of multiple sclerosis is
      undeniable, as well as the fact that injuries are factors of progression and
      deterioration of the disease, but never its cause. Consequently, injuries can
      cause only temporary disability, and not permanent. Nevertheless, the incidence
      of multiple sclerosis increases proportionally to the severity of injury. The
      length of the period from the occurrence of injury to possible demyelination is
      still not established. Studies and clinical reports point to the fact that in the
      evaluation of injury as a precipitating factor for the vulnerability of the blood
      brain barrier, the severity of the injury is of greater importance than its site.

PMID- 9650483
TI  - [The respiratory system--its self-cleaning system. General mechanisms of
      clearance].
AB  - The behaviour of particles and deposition in different parts of respiratory
      system are described. Listed are factors which contribute to the deposition of
      particles in the lungs and upper areas of the respiratory system. The general
      mechanisms of lung clearance and their action such as cough, mucociliary
      transport, alveolar clearance and immunological system are reported. Particularly
      is stressed the necessity of coordination of all defense mechanisms in order to
      maintain normal respiratory function.

PMID- 9650484
TI  - [Paraneoplastic autoimmune neurologic syndromes].
AB  - Paraneoplastic neurologic syndromes are group of distant nonmetastatic neurologic
      manifestations of malignant diseases. In last few decades a major advance in
      understanding their etiology and pathogenesis has been achieved. Larger series of
      patients have been reported allowing more detailed clinical research of
      particular syndromes. To practicing physician they can be a first clinical sign
      in diagnosing a neoplasm. In these conditions immunologists can test new theories
      in tumor immunology and autoimmunity. To the oncologists they can serve as a
      model in development of new modalities of treating malignant tumors. Neurologic
      syndromes that can be explained as autoimmune reactions initiated by the
      development of malignancy are presented in this paper.

PMID- 9650485
TI  - [Group psychotherapy in the treatment of post-traumatic stress disorder].
AB  - Working with psychotraumatized war veterans we perceived their extremely
      regressive position, which is accompanied by several destructive and
      autodestructive compulsions. Facing the multiple traumatic experiences which they
      lived through, a certain degree of regression has been appearing, since even a
      satisfying "nourishing-indulgence of their needs" cannot completely make up for
      their pre-war position. In this way occurred the splitting between ideal
      (introjected) object and real object, in which were projected all bad
      experiences, and which is still persecuting and wants to destroy. Through
      interactions between all group members of traumatized patients we analyzed the
      phenomena and the specificities of these groups-particularly their regressive
      position. The aim of the group psychotherapy was to enable progressive overcoming
      of regressive position and transition into a more mature stage of development,
      thus creating a favorable climate for growing up and independence.

PMID- 9650486
TI  - [In memory of Dr. Danko Riessner].

PMID- 9650487
TI  - Schools misinterpret immunization rules.

PMID- 9650488
TI  - Court rules insurer employee was practicing medicine.

PMID- 9650489
TI  - The liquidation of PIC and PIE: what physicians need to know.

PMID- 9650490
TI  - Should medications be crushed?

PMID- 9650491
TI  - Delaware Valley organ donation system is national model.

PMID- 9650492
TI  - [The future of immunology and clinical allergy in Mexico].

PMID- 9650493
TI  - [Oropharyngeal bacterial flora in asthmatic and health subjects].
AB  - MATERIAL AND METHODS: It was carried out cultivation of oozing pharyngeal to 248
      fellows, 128 of them were asthmatic and 120 seemingly healthy. From group of
      asthmatic 55.46% they correspond to the masculine sex and 44.54% to the feminine;
      72.97% they present more than two sharp squares of asthma per month. RESULTS: In
      the cultivation of 107 asthmatic the presence of germs is reported like:
      Staphylococcus aureus positive 43.56% (p = NS), the Streptococcus betahemolytic
      72.97% (p = 0.001), Candida albicans 70.58% (p = 0.004), Streptococcus alpha
      haemolyticus 61.42% (p = 0.008). CONCLUSIONS: When they exist more than two germs
      in a same individual frequently the Staphylococcus aureus is detected with the
      Streptococcus beta hemolytic 42.10% or with the Candida albicans 31.57%. We
      proposes to magnify the problem to which the patients face in order to order a
      medication or examine of laboratory with opportunity and when we hoped to obtain
      the good benefit for the health of the population.

PMID- 9650494
TI  - [Comparison of 4 skin prick tests to detect immediate hypersensitivity].
AB  - AIMS: To diagnostic allergic diseases it's necessary an adequate history, and in
      vivo or in vitro test, to determine specific IgE. The skin prick test are the
      best for this, because are more sensitive, economic and quick to do. However
      there are variability in results with the different instruments to do it (the
      Morrow-Brown (MB), needle, Prick lancet (L)t Multi-Test (MT), and the Doutip
      Test). To consider this instruments how adequate diagnostic proceedings, we
      should evaluate some characteristics. Because it, our objective was to evaluate
      precision, sensitivity, specificity and patient preference by each one. METHOD:
      Prospective study in 20 patients with asthma or allergic rhinitis who comes to
      the allergy service of Hospital Infantil de Mexico Federico Gomez. We analyzed
      skin prick test with DT, MB, MT and L on the back surface with histamine in five
      times and glicerosaline in one. We measured wheel and flare diameters 15 minutes
      after applications. We consider positive results if medium diameter of wheel was
      3 mm or flare 10 mm. Precision was measured by coefficient of variation of wheel
      with histamine with each instrument. Patient preference was considered in
      relation to low grade of discomfort with each one. Precision was compared by two-
      vias varianza analysis. No parametric Friedman test was used to compared patient
      preference. RESULTS: We studied 20 patients, 40% was females and 60% males. The
      ages were 10 to 16 years old Promedio wheal histamine diameter was to MB = 5.1 +/
      1.1, L = 6.1 +/- 0.8, DT = 6.7 +/- 0.9, MT = 6.3 +/- 1.5; promedio flare
      diameter with histamine was to MB: 15.9 +/- 4.2, L: 19.0 +/- 4.8, DT = 21.9 +/-
      4.8, MT = 18 +/- 6.9. Sensibility of DT was 100%, L = 99%, MT = 97% and MB 95%.
      The specificity of MB was 90%, L = 70%, MT = 41.6% and DT 30%. DT coefficient of
      variation was 15.6%, L: 17.3%, MT = 24.4% and MB 24.6%. CONCLUSIONS: In our study
      more sensitive device was DT, more specific was MB and more precise was DT.
      Patients preferred the lancet, because they had less discomfort when used it.

PMID- 9650495
TI  - [Effect of levamisole on microbicidal activity and chemotaxis in
      polymorphonuclear cells].
AB  - AIMS: Neonatal septicemia may have a mortality of 20% in newborns small for their
      gestational age. This susceptibility for infections has been explained by
      immunological disorders. The aim of this study to know the effect of levamisole
      on the functions of chemotaxis and bacterial activity of PMN cells in newborns
      small for their-gestational age. MATERIAL AND METHODS: Twenty full-term newborns
      were studied. Ten of them were small for their-gestational age, and the other 10
      had body weight within the normal range. Microbicidal activity and chemotaxis
      were measured, and comparisons between groups were made with non-parametric
      statistical tests. RESULTS: In the group of newborns small for their-gestational
      age. Microbicidal activity was similar to control group, but chemotactic activity
      was reduced (p < 0.05).

PMID- 9650496
TI  - [Development of a questionnaire to assess the knowledge on infantile++ asthma in
      medical students].
AB  - Asthma is the most common chronic childhood illness. The increasing morbidity and
      mortality are striking contrast to major scientific advances in our understanding
      of asthma. It is now regarded as a chronic rather than a episodic illness and the
      major factors contributing to asthma morbidity and mortality are underdiagnosis
      and inappropriate treatment. The majority of children with asthma are cared for
      by nonspecialist physicians. Studies have shown that only small proportions of
      practitioners have an adequate understanding of the changing concepts of asthma
      management. We development an asthma knowledge questionnaire based on "Guidelines
      and the Practice Parameters for the Diagnosis and Management of Asthma" of The
      National Heart, Lung, and Blood Institute. The questionnaires include 25
      questions on definition, physiopathology, diagnosis and treatment.

PMID- 9650497
TI  - [Kartagener syndrome (type 1 primary ciliary dyskinesia). Report of a case and
      review of the literature].

PMID- 9650498
TI  - [A single-center controlled clinical study with Sandimmune Neoral after kidney
      transplantation].
AB  - The authors compared in a controlled clinical study two groups of patients after
      a first renal transplantation treated by triple drug immunosuppressive therapy.
      In a group of 31 patients the triple combination comprised Sandimmune Neoral. In
      the control group there were 30 patients who received Sandimmune. No differences
      were found between the two groups as regards the effectiveness of this treatment
      and the authors did not confirm a lower incidence of rejections described in
      patients treated with Sandimmune Neoral. They confirmed, however, a lower
      interindividual variability of Cy-A levels assessed specifically in patients
      treated with Sandimmune Neoral.

PMID- 9650499
TI  - [The effects of Carvedilol, a beta-blocker, in experimental ischemia-reperfusion
      kidney injury].
AB  - Carvedilol is a recently introduced drug with multiple action with a non
      selective beta-antiadrenergic and selective alpha1-antiadrenergic action used for
      treatment of mild to medium severe hypertension. The authors investigated in
      their experiments the protective effect of carvedilol under conditions of
      ischaemia-reperfusion of the kidney in the laboratory rat. The animals were
      divided into four groups 1. the control group was fed a diet without carvedilol
      for a period of two weeks. Groups 2, 3 and 4 were fed for two weeks a diet
      containing carvedilol, 1-3-10 mg/kg/day resp. After completed medication in all
      animals ischaemia of the kidney was induced (60 min.) with subsequent reperfusion
      (10 min.) Then the animals were sacrificed, the kidney was removed for
      histopathological examination, in blood the malondialdehyde (MDA) level was
      assessed. The conclusions of the investigation indicate a marked protective
      effect of the administered preparation. Carvedilol prevents the disintegration of
      tubular epithelia, pycnosis of the nuclei, and reduced the development of
      oedematous changes. These findings correlate with MDA levels.

PMID- 9650500
TI  - [Analysis of perception in patients during an acute attack of bronchial asthma].
AB  - An analysis of subjective sensations during an asthmatic attack in 51 asthma
      patients was performed. A difficult inspiration or inspiration and expiration was
      the most prevalent sensation, while isolated difficult expiration was only sparse
      finding. A tightness on the chest was often noticed as well. The probable
      explanation for these observation could be the breathing a high lung volume
      (hyperinflation), caused by closing small airway a mostly due to
      bronchoconstriction during the asthmatic attack. The authors suggest not to
      generally use the term "expiratory breathlessness" when describing the clinical
      picture of an asthmatic attack.

PMID- 9650501
TI  - [Levels of CK MB mass in patients with acute myocardial infarct treatedwith
      fibrinolysis. Comparison with levels of CK, CKMB, CKMB mass and troponin T in the
      diagnosis of coronary ischemia].
AB  - In a group of 26 patients with AIM the CKMB value was raised above the
      discrimination level already on admission--on average 2.7 +/- 1.4 hours after
      development of ischaemic pain--in 46% patients. The maximal value of CKMB mass
      was achieved in the group with probable reperfusion 12.1 +/- 3.8 hours after the
      development of ischaemic pain and this value was elevated in relation to the
      discrimination value 41.5 +/- 17x and in relation to the so-called basal value
      145 +/- 117x. In the group without probable reperfusion the maximal value was
      achieved significantly later, after 19.8 +/- hours and was elevated in relation
      to the discrimination value 31 +/- 17x and in relation to the final value 84 +/-
      42 times. The value of CKMB mass increased above the discrimination limit from
      the onset of ischaemic pain after 4.0 +/- 1.5 and after 5.7 +/- 3 hours in the
      group with probable and without probable reperfusion and declined below the
      discrimination limit after 00 +/- 60 and 119 +/- 98.0 hours in the same groups.
      On comparison of CK, CKBM, CKBM mass and troponin T on admission the CKMB mass
      value was elevated in 46% patients, the value of CK in 23%, of CKMB in 27% and
      the troponin T value in 96% patients. With regard to the assembled experience
      that haemolytic serum raises false troponin T values, the percentage of elevated
      troponin T values on admission declines from the original 96% to 81% when all
      haemolytic samples are eliminated. The time of reaching maximal values of CKMB
      mass in patients with AIM and probable reperfusion was significantly shorter than
      in CK values and is similar as in CKMB values. The time taken to raise the CKBMB
      mass value above the discrimination value is significantly shorter than the time
      taken by CK levels, but significantly longer than the time before troponin T
      levels are raised. The time of total elevation of CKMB mass levels above the
      discrimination limit does not differ from the time taken to raise CK values, it
      is however shorter than the increase of troponin T values, although the exact
      time of persistence of raised levels of troponin T was not assessed in our work.
      The time of increase above and decrease below the discrimination limit was not
      assessed in CKMB values. Based on mutual comparison of the impact of indicators
      for assessment of the diagnosis of ischaemic heart attacks the authors consider
      it best regardless of financial costs--to assess troponin T, possibly along with
      levels of CKMB mass.

PMID- 9650502
TI  - [The effect of 4 years' of hypolipemic treatment on the width of the common
      carotid artery intima in patients with familial hyperlipidemias].
AB  - Sixty-four patients with familial hyperlipoproteinaemia were treated for almost
      four years by dietetic treatment and various hypolipidaemic drugs. In 25 patients
      with familial hypercholesterolaemia who had clinical signs of ischaemic heart
      disease total and LDL-cholesterol declined and the width of the intima of the
      common carotid artery diminished from 0.78 mm to 0.69 mm (p = 0.004). In the
      above artery the maximal flow rate of blood declined. The increase was, however,
      not statistically significant. In 12 patients with familial hypercholesterolaemia
      who suffered from ischaemic heart disease the width of the intima of the common
      carotid artery and maximum flow rate did not change, however, the diameter of the
      artery increased (from 6.3 to 6.6 mm, p = 0.034). In 27 patients with familial
      combined hyperlipidaemia during the drop of cholesterol, LDL-cholesterol and
      triacylglycerols the width of the intima of the common carotid artery diminished
      (from 0.72 to 0.67 mm, p = 0.044), the diameter of the artery increased (from 6.1
      to 6.4 mm, p = 0.014). The authors assume that the reduction of the width of the
      intima during hypolipidaemic treatment reflected the decline of cholesterol in
      the arterial wall and is a favourable sign which indicates possible regression of
      atherosclerosis.

PMID- 9650503
TI  - [10 years' of care of adult patients with cystic fibrosis].
AB  - The authors summarized the results of ten years care of adult patients with
      cystic fibrosis (CF). They treated a total of 45 patients incl. 26 men and 19
      women. Nineteen patients (42%) died. The most frequent cause of admission to
      hospital was respiratory infection (84%), planned antibiotic treatment (6.5%),
      pneumothorax (6%) and haemoptysis (4%). In all patients impaired ventilation of
      the obstructive type was found. The mean annual decline of FEV1 was 0.173 +/-
      0.194 l, VC 0.303 +/- 0.323 l. The authors did not find a significant difference
      between live and dead patients. The mean annual increase of PaCO2 was 0.5 +/-
      0.87 kPa, the mean annual decrease of PaO2 was 0.6 +/- 0.96 kPa. The difference
      of values in dead and live patients was significant. CF still remains an
      incurable disease. It is, however, possible by comprehensive treatment to prolong
      the patients life and to improve its quality.

PMID- 9650504
TI  - [Endogenous levels of somatostatin, C-peptide and insulin in acute pancreatitis].
AB  - The authors compared in seven patients with acute pancreatitis the levels of
      endogenous somatostatin, insulin and C-peptide to assess their mutual correlation
      and relation to the development of the disease and serum amalyse levels. The
      results were compared with values recorded in 11 healthy volunteers. The levels
      of endogenous somatostatin were in patients with acute pancreatitis significantly
      higher (p < 0.05) than in the control group. The authors found an inverse
      relationship between the somatostatin and amylase level (correlation coefficient
      0.75). They did not observe a significant correlation between somatostatin and
      insulin levels nor between somatostatin and C-peptide levels. The elevated
      somatostatin level may be due to the counteregulatory reaction during secretion,
      stimulated by endogenous or exogenous factors (cholecystokinin, alcohol, food).

PMID- 9650505
TI  - [Significance of vegetative nerve tone in patients with vasovagal
      neurocardiogenic syncope].
AB  - The timely provided and precise diagnostic of the syncopal states as well as
      their causal therapy is a main subject of many medical branches interest within
      last time. Our work was concentrated on a vasovagal neurocardiogenic syncope. The
      definition of the vegetative nervous tonus participation on its development by a
      method of evaluation of the heart rate variability as well as the review of a
      possibility to the application of quantification these results to a prediction of
      vasovagal reaction, respective of its malignant variant, was the main aim of our
      effort. Our results enable a conclusion, that the observation of aquiet autonomic
      nervous tonus does not represent a contribution to a differential diagnostics of
      syncope of uncleared etiology with a suspicion on vasovagalous neurocardiogenous
      syncope, because the basal vagal tonus does not allow the forecast of head
      upright tilt table testing results as well as determination of the type of
      respectively provocated vasovagal neurocardiogenic syncope. However, a
      correlation between an actual reactive vageous tonus surveyed by the SD index for
      patients with vasovagal neurocardiogenic syncope of the type I and IIa in
      comparison with healthy persons, was found out. It allows to draw a conclusion,
      that the vasovagal neurocardiogenic syncope is not homogeneous nosological unit,
      what results in efforts to it's more detailed classification.

PMID- 9650506
TI  - [Plasminogen activator inhibitor (PAI-1) and markers of endothelial dysfunction
      in patients with diabetes mellitus].
AB  - The authors examined 25 patients with diabetes mellitus type 2 (NIDDM) without
      vascular complications, treated by sulphonyl urea preparations, 12
      hyperinsulinaemic (HI) non-diabetic subjects and 11 normoinsulinaemic healthy
      subject s. Patients with NIDDM and HI non-diabetics had significantly elevated
      PAI-1 levels which correlated with the C-peptide level (r = 0.519, p < 0.001),
      triacylglycerols (TG) (r = 0.685, p < 0.001), BMI (r = 0.607, p < 0.001) and
      levels of endothelial markers such as von Willebrand s factor and thrombomodulin
      (TM). In the group of patients with NIDDM no relationship of PAI-1 and C-peptide
      was found and a significant correlation was found with TM levels (r = 0.609, p =
      0.001) and TG levels (r = 0.476, p = 0.046). The results suggest that the
      endothelial department has an effect on the regulation of PAI-1 levels in
      patients with NIDDM.

PMID- 9650507
TI  - [The effect of sulodexide, a glycosaminoglycan, on albuminuria in diabetic
      patients].
AB  - The authors administered to type 1 diabetics (n = 15) or type 2 diabetics (n =
      20) with microalbuminuria or macroalbuminuria for a period of 15 days i.m. doses
      of sulodexide (Vessel Due F), 600 i.u. (i.e. 60 mg). The evaluation of the whole
      group revealed a statistically significant reduction of the original mean value
      of albuminuria (509 +/- 127 ug/min) already during the first week of sulodexide
      administration (382 +/- 105). A further decrease was recorded after the second
      and third week of treatment (326 +/- 89, 319 +/- 85 ug/min). While in diabetics
      with microalbuminuria < 100 micrograms/min the mean levels of excreted albumin
      were not affected, in diabetics with macroalbuminuria 200 ug/min a significant
      reduction of albuminuria persisted (p < 0.001) achieved during sulodexide
      treatment persisted for three weeks after completed treatment. No differences
      were found between the results of type 1 and type 2 diabetics. CONCLUSION:
      Seventy-seven per cent type 1 and type 2 diabetics responded to parenteral
      sulodexide administration for 15 days by a statistically significant reduction of
      albumin.

PMID- 9650508
TI  - [Calciphylaxis in a patient on long-term dialysis].
AB  - Calciphylaxis is a special form of soft tissue calcification (in particular blood
      vessels), affecting specially patients with chronic renal insufficiency and
      associated secondary hyperparathyroidism. Most severely affected are small
      arteries with a diameter of 0.2-0.5 mm at the interface of the corium and
      subcutaneous layer. Calcification of the vascular media with subsequent narrowing
      of the lumen causes ischaemic changes manifested by the development of painful
      reddish-violet spots on the skin with necrosis and ulcerations. The authors
      describe the case of a 73-year-old diabetic female patient with regular
      dialyzation treatment. The patient developed reddish-violet spots on the lower
      extremities shortly before admission to hospital. At the site of the spots
      rapidly progressing necroses developed. The cause of these ischaemic changes were
      calciphylactic changes confirmed on post-mortem examination and by histological
      examination.

PMID- 9650509
TI  - [Autologous transplantation of peripheral hematopoietic cells in a patient with
      multiple myeloma and renal insufficiency].
AB  - High dosage melfalan chemotherapy with subsequent autologous blood stem cell
      transplantation in suitably selected patients with multiple myeloma greatly
      increases the probability that complete remission will be achieved and it
      prolongs the mean survival period as compared with classical chemotherapy. Till
      recently patients with multiple myeloma and renal insufficiency were not included
      in transplantation programmes. Only recently several papers were published abroad
      which indicate the possibility to implement transplantations also in these
      patients. The authors describe the treatment, incl. the first autologous
      transplantation of blood stem cells in a patient with multiple myeloma and renal
      insufficiency.

PMID- 9650510
TI  - [Stress echocardiography in "non-ischemic myocardial disease"].
AB  - Stress echocardiography is nowadays an integral part of the diagnosis of
      ischaemic heart disease. In the submitted review the authors draw attention to
      the fact that ischaemic heart disease is no longer the domain of stress
      echocardiography. In recent years the interest of cardiologists in this method
      increased also in other cardiac diseases. Based on the appropriate
      pathophysiological mechanism of cardiac affection stress echocardiography is used
      to test left ventricular function after a dynamic or pharmacological stress, i.e.
      increased cardiac activity and cardiac minute volume in a number of heart
      diseases where we must know the extent of left ventricular affection and the
      functional reserve of the myocardium. These tests were also introduced to
      evaluate the impact of valvular disease and function of artificial grafts to
      evaluate left ventricular function in the transplanted heart. Stress
      echocardiograph holds its place also in paediatrics.

PMID- 9650511
TI  - [Present trends in the pathogenesis, diagnosis and therapy of vasovagal syncope].
AB  - Vasovagal syncope is the most frequent cause of syncopal conditions. In its
      pathogenesis autonomic nervous, neurohumoral, cerebrovascular and other
      mechanisms participate. The gold standard in the diagnosis of vasovagal syncope
      is in recent years the head up tilt test. In treatment pharmacotherapy, cardiac
      pacing or their combination can be used.

PMID- 9650513
TI  - Annonaceous acetogenins as natural pesticides: potent toxicity against
      insecticide-susceptible and -resistant German cockroaches (Dictyoptera:
      Blattellidae).
AB  - Six compounds, representing the mono-tetrahydrofuran (THF) (gigantetrocin A,
      annomontacin), adjacent bis-THF (asimicin, parviflorin), and nonadjacent bis-THF
      (sylvaticin, bullatalicin) classes of annonaceous acetogenins, were compared with
      technical grades of synthetic amidinohydrazone (hydramethylnon), carbamate
      (propoxur, bendiocarb), organophosphate (chlorpyrifos), and pyrethroid
      (cypermethrin) insecticides to determine their dietary toxicities to insecticide
      resistant and insecticide-susceptible strains of the German cockroach, Blattella
      germanica (L.). Differential susceptibility occurred among B. germanica nymphs of
      both strains to this variety of the acetogenins and the 5 conventional synthetic
      insecticides. The speed of kill (LT50) values against insecticide-susceptible and
      insecticide-resistant 2nd and 5th instars permitted ranking of all 11 compounds.
      The adjacent bis-THF acetogenins showed the highest potency among the 3
      acetogenin classes. The acetogenins caused high percentages of mortality and
      delays in development of the 5th instars of both strains. Insecticide-susceptible
      nymphal development was mainly affected by gigantetrocin A and annomontacin,
      whereas insecticide-resistant nymphal development was mainly affected by
      gigantetrocin A and bullatalicin. Most tested acetogenins performed better than
      the conventional insecticides against both stages of both strains. No growth
      regulation effects were caused by any of the compounds tested. Low resistance
      ratios were obtained for most compounds (except chlorpyrifos). Low resistance
      ratios values for 2nd instars ranged from 0.9 to 2.2 with the natural acetogenins
      and from 1.0 to 3.8 with the synthetic compounds; the 5th instars ranged from 0.2
      to 3.9 with the natural acetogenins and from 0.6 to 8.0 with the synthetic
      compounds. Insecticidal properties and characteristics of acetogenins and the
      possible use of acetogenins in baits for cockroach control are discussed.

PMID- 9650514
TI  - Delivery of ivermectin by injectable microspheres.
AB  - A bioabsorbable, injectable microsphere formulation containing ivermectin in poly
      (lactide-co-glycolide) copolymer (PLA/PGA) was developed to provide long-lasting
      delivery of the drug for control of livestock pests. A solvent-evaporation
      technique was used to produce the spherical beads containing approximately 30%
      ivermectin and ranging in size from 25-250 microns. The pattern of delivery of
      the drug into the blood stream of Spanish goats was characterized for a 50:50
      PLA/PGA, a 90:10 PLA/PGA copolymer formulation, and a PLA monomer formulation.
      When the 50:50 PLA/PGA formulation was used in cattle at the rate of 2 mg (AI)/kg
      body weight, 2 peaks of 45-50 ppb of ivermectin in serum were observed. The 1st
      peak was at approximately 1 wk after injection and the 2nd peak, which was
      broader than the 1st, occurred at approximately 6-7 wk after injection.
      Percentage of inhibition of estimated larvae for the lone star tick, Amblyomma
      americanum (L.), placed on treated cattle was 100% for the first 8 wk after
      injection and was 75, 57, 46 and 44% for wk 9, 10, 11, and 12, respectively. The
      treatment provided 98-100% control of larval horn flies, Haematobia irritans
      (L.), in the manure of treated cattle for 10 wk. The bioassay results against
      lone star ticks and larval horn flies were in agreement with the serum
      concentration data. The injectable microsphere formulation of ivermectin should
      be useful in a variety of other applications ranging from the control of
      Boophilus spp. ticks in south Texas to heartworms in pets.

PMID- 9650515
TI  - Typhaea stercorea (Coleoptera: Mycetophagidae), a carrier of Salmonella enterica
      serovar Infantis in a Danish broiler house.
AB  - In December 1994, Salmonella enterica serovar Infantis (S. Infantis) was
      accidentally introduced into a Danish broiler house by stocking an S. Infantis
      infected broiler flock of 39,900 day-old chicks. At the time of the study, the
      infection had persisted through 6 broiler cycles. Typhaea stercorea (L.), the
      hairy fungus beetle, was found in large quantities inside and around the broiler
      house. Various attempts to control the beetle had failed; T. stercorea had been
      uncontrollable on the farm since Alphitobius diaperinus (Panzer), the lesser
      mealworm, was eradicated approximately 10 yr earlier. We investigated the ability
      of T. stercorea to act as a carrier of S. Infantis in the broiler house between 2
      broiler cycles. We examined the empty, cleaned, and disinfected broiler house for
      S. Infantis 3 d before stocking the 7th broiler flock, and S. Infantis was
      isolated from the beetles only. Of 20 singly examined T. stercorea, 9 (45%) were
      S. Infantis positive. A rapid spread of the infection was seen in the 7th broiler
      flock; 100% of the culled chicks were S. Infantis positive 3 d after stocking.
      Under experimental conditions chicks were observed eating beetles, and when 5 d
      old, specified pathogen-free chicks were fed with S. Infantis-positive T.
      stercorea collected from the broiler house, all 5 chicks became infected in 4 d.
      We conclude that T. stercorea may act as a potential carrier of S. Infantis
      between successive broiler cycles.

PMID- 9650518
TI  - Migraine. More than a headache.

PMID- 9650517
TI  - Prevention. Who should take cholesterol-lowering drugs?

PMID- 9650519
TI  - Recommendations updated for hypertension.

PMID- 9650520
TI  - My teeth look yellow and I've considered bleaching them. Can I do this at home or
      do I need to go to the dentist?

PMID- 9650522
TI  - Irradiation may make meat supply safer.

PMID- 9650521
TI  - Gaining weight increases breast cancer risk.

PMID- 9650523
TI  - Clear thinking on tamoxifen.

PMID- 9650524
TI  - Taking the sting out of shingles.

PMID- 9650525
TI  - Cataracts: when is surgery necessary?

PMID- 9650526
TI  - Taking advantage of gallstone advances.

PMID- 9650527
TI  - Do cholesterol-lowering drugs reduce stroke risk?

PMID- 9650528
TI  - Who needs to take antibiotics before dental work?

PMID- 9650529
TI  - Is it normal for hives to last longer than a month?

PMID- 9650530
TI  - Cloning of intestinal phospholipase A2 from intestinal epithelial RNA by
      differential display PCR.
AB  - Differential display polymerase chain reaction (DD-PCR) is a powerful technique
      for comparing gene expression between cell types, or between stages of
      development or differentiation. Differentially expressed genes may be cloned and
      analysed further. Here we extend the use of DD-PCR to analyse differences in gene
      expression between two complex epithelia: that of the small intestine and of the
      large intestine. The aim of this study was to identify genes expressed
      preferentially in Paneth cells. Paneth cells are secretory epithelial cells
      putatively involved in host defense and regulation of crypt cell proliferation
      and are found at the base of the small intestinal crypts adjacent to the stem
      cell zone. Of 34 clones that were analysed, partial sequencing identified two
      clones related to known Paneth cell products: a homologue of secretory
      phospholipase A2 (clone B1) and a homologue of a neutrophil defensin (clone C5).
      B1 was strongly expressed in Paneth cells, as demonstrated by in-situ
      hybridization. B1 was also expressed at a lower level in the large intestinal
      epithelium. A full length B1 cDNA clone was isolated and sequenced, and shown to
      be highly homologous to type II secretory phospholipase A2 genes, and almost
      identical to the enhancing factor gene and the putative gene for the MOM-1 locus.
      B1 expression is limited to the intestinal tract, and we propose that it be
      designated intestinal phospholipase A2, or i-PLA2. The method we describe is well
      suited to the rapid identification of genes expressed exclusively or
      predominantly in Paneth cells.

PMID- 9650531
TI  - Unbalanced growth in mouse cells with amplified dhfr genes.
AB  - When grown in the absence of methotrexate, cells carrying unstably amplified
      dihydrofolate reductase (dhfr) genes have a growth disadvantage that is a
      function of their level of gene amplification. Although this growth disadvantage
      is thought to drive the loss of unstably amplified dhfr genes in the absence of
      methotrexate, its mechanism is not understood. The present studies of murine cell
      lines with different levels of dhfr gene amplification demonstrate that such
      cells experience increased unbalanced growth (excess RNA and protein content
      relative to DNA content) with increased levels of dhfr gene amplification.
      Stathmokinetic analysis of a cell line with unstably amplified dhfr genes showed
      that the unbalanced growth was associated with a very low rate of G1/S transit,
      which suggests that amplified DNA sequences may activate a cell cycle checkpoint
      at the G1/S boundary. Hydroxyurea, which is known to induce rapid elimination of
      amplified genes at sub-cytotoxic concentrations, also inhibits the cell cycle at
      the G1/S transition and causes unbalanced growth. Earlier work has shown that
      hydroxyurea selectively targets those cells within the heterogeneous drug
      resistant cell populations which have the highest amplified gene dosage. The
      finding that unstable gene amplification and hydroxyurea have similar effects on
      the cell suggests that hydroxyurea may achieve this selective targeting by
      pushing those cells with the highest levels of gene amplification over a critical
      stress threshold to cause growth arrest or cell death.

PMID- 9650532
TI  - Roles of epidemiology, pathology, molecular biology, and biomarkers in the
      investigation of occupational lung cancer.
AB  - The pathology and molecular biology of lung cancer demonstrate that these tumors
      evolve through a series of mutations, molecular changes, and corresponding
      morphologic changes. To elucidate how occupational and environmental factors
      influence lung cancer histogenesis it is important not only to understand
      epidemiology and the interactions between etiologic agents but also to integrate
      information from pathology, biochemistry and molecular biology. This review
      focuses on the range of techniques currently available for characterizing lung
      cancer and how their prudent use can be beneficial in the identification of
      occupational carcinogens. Because many occupational and environmental lung
      cancers are caused by multiple etiologic agents, the integration of histology
      with cellular, biochemical and molecular biomarker techniques may provide new
      approaches for understanding the disease process.

PMID- 9650533
TI  - The alveolar macrophage as a model of calcium signaling in oxidative stress.
AB  - Regulation of the free intracellular calcium concentration, [Ca2+]i, plays a
      major role in physiological signal transduction. Many of the essential enzymes in
      signaling cascades are Ca(2+)-dependent, as are numerous proteins that
      participate in the regulated function. Oxidative stress, which for many years was
      considered synonymous with cell and tissue injury, has more recently been
      demonstrated to alter signal transduction in both positive and negative
      directions. The realization that hydrogen peroxide and lipid hydroperoxides are
      produced as part of normal metabolism has led to the proposal that these oxidants
      function as second messengers. Exposure to environmental and other agents that
      produce hydroperoxides or the addition of exogenous hydroperoxides also causes
      elevation of [Ca2+]i in some cells. At sublethal exposure to hydroperoxides, the
      elevation in [Ca2+]i can either alter or mimic physiological stimulation. In
      addition to endoplasmic reticulum, mitochondria, and the extracellular space, the
      phospholipid- and Ca(2+)-binding proteins known as annexins constitute a Ca2+
      pool from which this ion may be released under situations of oxidative stress. In
      this article, the source and consequences of Ca2+ elevation are reviewed with an
      emphasis on studies done with alveolar macrophages. These phagocytes, which
      modulate much of the physiological and immunological function of the lung, are
      susceptible targets for environmental oxidants.

PMID- 9650534
TI  - Need for dietary control by caloric restriction in rodent toxicology and
      carcinogenicity studies.
AB  - The conditions under which laboratory animals are maintained can powerfully
      influence the results of toxicological studies utilized for risk assessment.
      Nutrition is of importance in toxicological bioassays and research, because diet
      composition and the conditions under which it is fed can affect the metabolism
      and activity of xenobiotic test substances and alter the results and
      reproducibility of long-term studies. It is known that ad libitum (AL) overfed
      sedentary laboratory rodents suffer from an early onset of degenerative disease
      and diet-related tumors that lead to poor survival in chronic bioassays. AL-fed
      animals are not well-controlled subjects for any experimental studies.
      Examination of study-to-study variability in food consumption, body weight, and
      survival in carcinogenicity studies for the same strain or stock of rodents shows
      tremendous laboratory-to-laboratory variability. However, a significant
      correlation between average food (calorie) consumption, adult body weight, and
      survival has been clearly established. The use of moderate dietary restriction
      (DR) results in a better controlled rodent model with a lower incidence or
      delayed onset of spontaneous diseases and tumors. Operationally simple, moderate
      DR significantly improves survival, controls adult body weight and obesity,
      reduces age-related renal, endocrine, and cardiac diseases, increases exposure
      time, and increases the statistical sensitivity of these expensive, chronic
      bioassays to detect a true treatment effect. A moderate DR regimen of 70-75% of
      the maximum unrestricted AL food intake is recommended as a nutritionally
      intelligent, well-established method in conducting well-controlled toxicology and
      carcinogenicity studies.

PMID- 9650535
TI  - Chemical and epidemiological aspects of modified butter oil fractions.
AB  - Butter lipids are an important traditional source of dietary energy intake in the
      form of fat. Butter lost a sizable portion of its market share due to
      controversies associated with its cholesterol content and high percentage of long
      chain saturated fatty acids. Accordingly, the use of vegetable oils and their
      chemically manipulated counterparts such as those produced by partial
      hydrogenation or interestrification increased proportionally. However, beginning
      in 1940, researchers developed several procedures such as temperature-controlled
      crystallization, refractionation of crystallized butter oil solids, and
      supercritical carbon dioxide extraction to improve the acceptance of butter oil.
      Others proposed preparation of synthetic substitutes such as sucrose polyesters
      to reduce intestinal absorption of fatty acids, thus reducing caloric intake with
      concomitant reduction in serum cholesterol. The present review provides a summary
      of the efforts of several attempts to improve the acceptability of butter
      together with the anticipated epidemiological consequences of long-term
      consumption of altered butter oil to mammalian health.

PMID- 9650536
TI  - Use of angiotensin-converting enzyme inhibitors as monotherapy and in combination
      with diuretics and calcium channel blockers.
AB  - Angiotensin-converting enzyme (ACE) inhibitors have earned an important place in
      medical therapy since their discovery about two decades ago. This family of drug
      has grown tremendously since the introduction of captopril in 1981. There are
      currently more than 14 ACE inhibitors in the world and 9 are available in the
      United States. Although these agents share many similarities, they differ in
      their pharmacokinetic properties, approved indications, and cost. This paper
      provides guidance for selection of ACE inhibitors by examining the
      pharmacokinetics, pharmacodynamics, drug interactions, adverse effects, and cost
      of these agents. Combination products of ACE inhibitors with either diuretics or
      calcium channel blockers also are reviewed.

PMID- 9650537
TI  - Effect of multiple doses of rifampin on the [14C N-methyl] erythromycin breath
      test in healthy male volunteers.
AB  - The erythromycin breath test (EBT), which measures 14CO2 produced from [14C N
      methyl] erythromycin, is one of the most frequently employed measures to examine
      drug interactions involving cytochrome P450 3A4 (CYP3A). However, the
      reproducibility and reliability of this test, and the effects of drugs that alter
      CYP3A activity, continue to be defined. In this study, the reproducibility of the
      EBT was evaluated in eight healthy volunteers before and after oral
      administration of 600 mg of rifampin daily for 8 days. Two sequential EBT
      determinations performed 5 days apart before rifampin administration were highly
      reproducible. Rifampin induced CYP3A, reflected in a mean percent (+/- standard
      deviation) increase in EBT values of 86 +/- 30%. Recovery of enzyme function
      after discontinuation of rifampin for 17 days was manifested as a return of EBT
      values to preinduction levels. These results support the utility of EBT as a
      valid, reproducible, and reliable measure of CYP3A activity in vivo.

PMID- 9650538
TI  - Intravenous and oral propafenone for treatment of tachycardia in infants and
      children: pharmacokinetics and clinical response.
AB  - To elucidate contribution of an active metabolite to overall clinical responses
      to propafenone, steady-state disposition of propafenone and its active metabolite
      and the clinical responses to treatment were examined in pediatric patients
      receiving intravenous or oral propafenone. There were more than ten-fold
      interindividual differences in apparent clearance, resulting in a wide range of
      the steady-state trough plasma concentrations of propafenone. The active
      metabolite, 5-hydroxypropafenone, was detected in four of the six patients
      receiving oral propafenone; however, two neonates receiving oral propafenone and
      all eight receiving intravenous propafenone had no detectable levels of 5
      hydroxypropafenone in plasma. In nine patients for whom electrocardiographic
      (ECG) data were available, the PQ interval was significantly increased, whereas
      the QRS duration and the QTc interval were not. There was no close relationship
      between plasma concentrations of propafenone or 5-hydroxypropafenone and ECG
      parameters. Lack of good correlation between serum concentrations and clinical
      response precludes using a serum-concentration targeting strategy with
      propafenone therapy.

PMID- 9650539
TI  - Application of serum nicotine and plasma cotinine concentrations to assessment of
      nicotine replacement in light, moderate, and heavy smokers undergoing transdermal
      therapy.
AB  - As part of a clinical trial investigating the level of nicotine replacement with
      different doses of transdermal therapy for smoking cessation, peak and trough
      serum nicotine and plasma cotinine concentrations were measured in 70 subjects
      while they were actively smoking (baseline) and daily for 6 consecutive inpatient
      days while they were receiving transdermal nicotine. Subjects were randomly
      assigned to a daily 24-hour patch delivering a transdermal nicotine dose of 0,
      11, 22, or 44 mg and stratified by self-reported smoking rate as either light (10
      15 cigarettes per day), moderate (16-30 cigarettes per day), or heavy (>30
      cigarettes per day). Steady-state concentrations of nicotine and cotinine were
      attained in 1 and 3 days, respectively, at all doses and were independent of
      baseline smoking rate. Mean percentage replacement of nicotine was calculated by
      dividing steady-state peak nicotine or cotinine concentrations by their
      respective baseline concentrations. Significant underreplacement occurred in
      subjects receiving the 11 mg/day patch regardless of baseline smoking rate.
      Underreplacement also occurred in moderate and heavy smokers receiving 22 mg/day
      and in light smokers at this same dose. Complete replacement occurred only in
      subjects receiving the 44 mg/day patch. These results have several implications
      for transdermal nicotine therapy. First, with the higher nicotine and cotinine
      levels observed with heavier smoking, it is inherent that one size does not fit
      all, and there is a need to consider more individualization of dosage for
      nicotine patch therapy. Second, there is substantial underreplacement with the 22
      mg/day dose in moderate to heavy smokers and in some light smokers. Third, even
      with twice the usual dose (i.e., 44 mg/day), there was no accumulation of either
      nicotine or cotinine. Plasma cotinine levels after achievement of steady state
      (i.e., after 3 days of patch therapy) can be collected at any time and used to
      calculate percent replacement using baseline levels.

PMID- 9650540
TI  - Application of urine nicotine and cotinine excretion rates to assessment of
      nicotine replacement in light, moderate, and heavy smokers undergoing transdermal
      therapy.
AB  - As part of a clinical trial investigating the level of nicotine replacement with
      different doses of transdermal therapy for smoking cessation, urine excretion
      rates of nicotine and cotinine were measured in 70 subjects while they were
      actively smoking (baseline) and for 6 consecutive inpatient days while they were
      receiving transdermal nicotine therapy. Subjects were stratified according to
      baseline smoking rate as light (10-15 cigarettes per day), moderate (16-30
      cigarettes per day), or heavy (>30 cigarettes per day) smokers and randomly
      assigned to a daily 24-hour patch delivering a transdermal nicotine dose of 0,
      11, 22, or 44 mg. Steady-state excretion rates of nicotine and cotinine were
      attained in 2 and 3 days, respectively, at all doses and were independent of
      smoking rate. Percentage replacement of nicotine was calculated by dividing
      steady-state nicotine or cotinine excretion rates by their respective baseline
      excretion rates. Significant underreplacement occurred with the 11-mg/day dose,
      particularly in moderate and heavy smokers (<50%). At a dose of 22 mg/day,
      nicotine replacement was still <100% in the majority of subjects. Only at a dose
      of 44 mg/day did mean replacement exceed 100% regardless of baseline smoking
      rate.

PMID- 9650541
TI  - Pharmacokinetics of rifapentine in patients with varying degrees of hepatic
      dysfunction.
AB  - In this open-label investigation, the pharmacokinetics of rifapentine and its
      active metabolite, 25-desacetyl-rifapentine, were characterized in patients with
      varying degrees of hepatic dysfunction. Eight patients with mild-to-moderate
      chronic, stable hepatic dysfunction and seven patients with moderate-to-severe
      hepatic dysfunction received single oral 600-mg doses of rifapentine. Maximum
      plasma concentration of rifapentine was lower, time to maximum plasma
      concentration (tmax) was greater, and elimination half-life (t 1/2) was longer in
      the patients with moderate-to-severe hepatic dysfunction than in those with mild
      to-moderate dysfunction. However, mean area under the concentration-time curve
      extrapolated to infinity (AUC0-infinity) for the two groups was similar. AUC0
      infinity values in patients with hepatic dysfunction were 19% to 25% higher than
      values previously reported for healthy volunteers. The 25-desacetyl metabolite
      appeared in plasma slowly after the single oral dose of rifapentine. Similar to
      findings for the parent drug, comparable plasma exposures of 25-desacetyl
      rifapentine based on AUC0-infinity were found in the two groups of patients with
      mild-to-moderate and moderate-to-severe hepatic dysfunction. Rifapentine was well
      tolerated in this patient population, irrespective of the etiology or severity of
      hepatic dysfunction. These safety and pharmacokinetic results suggest that no
      dosage adjustments for rifapentine are needed in patients with hepatic
      impairment.

PMID- 9650542
TI  - Pharmacokinetics of intravenous and oral losartan in patients with heart failure.
AB  - The pharmacokinetics of a selective AT1-subtype, nonpeptide, orally active,
      angiotensin II receptor antagonist, losartan, were characterized in 11 patients
      with heart failure (New York Heart Association class II, n = 6; class III, n = 4;
      class IV, n = 1) after oral and intravenous administration. In these patients,
      average plasma clearance of losartan was 566 mL/min, volume of distribution at
      steady-state was 34 L, and terminal plasma half-life was 1.5 hours. Average
      bioavailability was 36%. No clinically significant accumulation of losartan or
      its active metabolite, EXP3174, occurred after multiple-dose oral administration
      for 7 to 8 days. Terminal plasma half-life of EXP3174 after oral administration
      of losartan was 7.6 hours. The pharmacokinetics of losartan in patients in this
      study appear to be similar to those in healthy subjects studied previously.

PMID- 9650543
TI  - Pharmacokinetics of acetazolamide in healthy volunteers after short- and long
      term exposure to high altitude.
AB  - Exposure to high altitude results in significant physiologic changes and may
      precipitate mountain sickness, ranging from mild symptoms above 2,500 m to severe
      symptoms above 4,000 m. In a previous study, changes in the pharmacokinetics of
      meperidine were observed after exposure to high altitude. This study was
      conducted to investigate whether similar changes occur for acetazolamide, which
      is prescribed for prophylaxis of acute mountain sickness. Acetazolamide 250 mg
      was administered orally to young, healthy male volunteers in groups of 12 each:
      those residing at sea level (group L), these same volunteers on the day after
      arrival at high altitude (4,360 m, group HA), and volunteers living at high
      altitude for 10 months or longer (group HC). Serial blood samples were collected
      for 24 hours and acetazolamide concentrations were measured in whole blood,
      plasma, and plasma water. The elimination rate constant (lambda z) was
      significantly increased in group HA compared with group L. Clearance uncorrected
      for bioavailability (Cl/F) increased significantly in group HA compared with
      group L, and further increased in group HC. Apparent volume of distribution
      (Vz/F) was decreased by 17% in group HA compared with group L, and increased by
      37% in group HC compared with group HA. Mean residence time (MRT) was
      significantly decreased in group HA compared with groups L and HC. Erythrocyte
      (RBC) uptake increased significantly after a significant increase in RBC count in
      group HC compared with group L. The extent of protein binding (EPB), however, was
      significantly decreased in group HA compared with groups L and HC. Free
      acetazolamide concentrations were significantly lower in group HC than in group L
      12 hours after administration. Based on these observations, it is suggested that
      patients travelling to high altitude, especially altitudes above 4,000 m, should
      be closely monitored and acetazolamide dosage adjusted as necessary.

PMID- 9650544
TI  - A novel recombinant soluble human thrombomodulin, ART-123, activates the protein
      C pathway in healthy male volunteers.
AB  - The effect of a novel recombinant soluble human thrombomodulin, ART-123, on
      protein C activation was investigated by measuring plasma prothrombinase activity
      in four healthy male volunteers. ART-123 at a dose of 0.3 mg was administered as
      a bolus intravenous injection for 1 minute. Plasma ART-123 concentration and
      prothrombinase activity were determined before and immediately, 24, and 48 hours
      after injection, and thromboelastography was recorded before and immediately and
      24 hours after injection. The mean elimination half-life was 19.82 +/- 2.10
      hours. Compared with pretreatment levels, ART-123 reduced prothrombinase activity
      by 44.2 +/- 11.7%, 52.1 +/- 10.8%, and 61.0 +/- 14.7%, respectively, immediately,
      24, and 48 hours after injection, suggesting that ART-123 activated the protein C
      pathway. ART-123 did not affect thromboelastography values. There were no
      abnormal findings for objective signs or laboratory tests, including blood
      pressure, heart rate, electrocardiogram, body temperature, hematology,
      coagulation and hemostatic parameters, blood chemistry, and urinalysis. Based on
      these observations, ART-123 at a dose of 0.3 mg can activate the protein C
      pathway in healthy volunteers.

PMID- 9650545
TI  - Effects of oral and intravenous terazosin and head-up tilt on blood pressure
      responses in patients with hypertension.
AB  - Terazosin is a selective alpha1-adrenoceptor antagonist. A double-blind,
      randomized, placebo-controlled, two-period study evaluated the effects of posture
      and of oral and intravenous administration of terazosin on blood pressure and
      heart rate in patients with hypertension. At least one week after withdrawal of
      all antihypertensive medications, 31 patients with sitting diastolic blood
      pressure of 95 to 114 mmHg were enrolled in the study. After a 24-hour, single
      blind, placebo lead-in phase, the patients were randomized to receive either oral
      terazosin (1 mg on day 1, 2 mg on day 2, and 5 mg on days 3 and 4), a 12-hour
      intravenous infusion of terazosin (2.5 mg, 5 mg, or 7.5 mg), or placebo for 4
      consecutive days. Head-up tilt (60 degrees for 20 minutes) evaluations were
      performed before and 0.5, 1.5, 2.5, 6, 12, and 16 hours after start of
      administration during the placebo lead-in phase and on each of the 4 days of the
      double-blind treatment phase. Blood pressure and heart rate were monitored every
      2 minutes during the 20-minute tilt. Statistically significantly larger mean
      changes in blood pressure and heart rate were observed with the 7.5-mg
      intravenous dose of terazosin compared with those after oral terazosin or
      placebo. With respect to intravenous terazosin, the orthostatic changes were
      maximal on the first day of the 4-day treatment and increased with increasing
      doses of terazosin. Maximum orthostatic changes in blood pressure after oral
      administration of terazosin were not significantly different from those observed
      with placebo. The most common treatment-emergent adverse events during tilt were
      dizziness and nausea. Dizziness occurred more frequently with intravenous
      terazosin than with oral terazosin. The results of this study indicate that oral
      dose titration of terazosin rather than a slower rate of terazosin infusion
      minimized the postural effects on blood pressure and associated symptoms during
      head-up tilt.

PMID- 9650546
TI  - Tramadol hydrochloride: analgesic efficacy compared with codeine, aspirin with
      codeine, and placebo after dental extraction.
AB  - Tramadol hydrochloride is a novel, centrally acting analgesic with two
      complementary mechanisms of action: opioid and aminergic. Relative to codeine,
      tramadol has similar analgesic properties but may have fewer constipating,
      euphoric, and respiratory depressant effects. A two-center randomized double
      blind controlled clinical trial was performed to assess the analgesic efficacy
      and reported side effects of tramadol 100 mg, tramadol 50 mg, codeine 60 mg,
      aspirin (ASA) 650 mg with codeine 60 mg, and placebo. Using a third molar
      extraction pain model, 200 healthy subjects were enrolled in a 6-hour evaluation
      after a single dose of drug. Of the 200 patients enrolled, seven provided
      incomplete efficacy data or discontinued prematurely and one was lost to follow
      up. Using standard measures of analgesia, including total pain relief score
      (TOTPAR), maximum pain relief score (MaxPAR), sum of pain intensity difference
      scores (SPID), peak pain intensity difference (Peak PID), remedication, and
      global evaluations, all active treatments were found to be numerically superior
      to placebo. ASA/codeine was found to be statistically superior to placebo for all
      measures of efficacy. Tramadol 100 mg was statistically superior to placebo for
      TOTPAR, SPID, and time of remedication, whereas tramadol 50 mg was statistically
      superior to placebo onlyfor remedication time. Codeine was not found to be
      statistically superior to placebo for any efficacy measure. A greater TOTPAR
      response compared with all other active measures was seen for ASA/codeine during
      the first 3 hours of study. The 6-hour TOTPAR scores for the tramadol groups and
      ASA/ codeine group were not significantly different. Gastrointestinal side
      effects (nausea, dysphagia, vomiting) were reported more frequently with tramadol
      100 mg, ASA/ codeine, and codeine 60 mg than with placebo.

PMID- 9650547
TI  - Pentoxifylline potentiates in vitro lymphocyte suppression by glucocorticoids and
      immunosuppressive drugs.
AB  - Pentoxifylline, which has immunomodulatory effects in addition to its better
      known rheologic effects, might potentiate the effectiveness of traditional
      immunosuppressive drugs. We therefore studied the suppressive effect of
      pentoxifylline in combination with clinically relevant concentrations of
      prednisolone, methylprednisolone, cyclosporine, tacrolimus, rapamycin, and
      mycophenolic acid on mitogen-stimulated lymphocytes from 29 patients with
      glomerular diseases. Inhibition of lymphocyte proliferation obtained with 10(-7)
      and 10(-8) mol/L concentrations of the glucocorticoids and with 300 ng/mL
      cyclosporine was significantly increased when each was combined with 5, 25, or 50
      microg/mL of pentoxifylline. The additive inhibitory effect of pentoxifylline in
      combination with 10(-7) mol/L glucocorticoids was inversely proportional to the
      inhibitory effect of the 10(-7) mol/L concentration of glucocorticoid alone,
      suggesting that the less sensitive the patient's cells, the greater the
      potentiation by pentoxifylline. The greatest degree of potentiation by
      pentoxifylline occurred when combined with the lower (10(-8) mol/L) concentration
      of glucocorticoids. Pentoxifylline also significantly increased lymphocyte
      suppression in combination with 150 and 300 ng/mL concentrations of cyclosporine,
      5 ng/mL of tacrolimus, 2.5 x 10(-7) mol/L mycophenolic acid, and 10 ng/mL of
      rapamycin. These in vitro results suggest that pentoxifylline might have steroid
      sparing effects and contribute to improved clinical outcomes from
      immunosuppressive treatment of renal diseases.

PMID- 9650548
TI  - High resolution deletion mapping reveals frequent allelic losses at the DNA
      mismatch repair loci hMLH1 and hMSH3 in non-small cell lung cancer.
AB  - To study the involvement of DNA mismatch repair genes in non-small cell lung
      cancer, matched normal and tumoral DNA samples from 31 patients were analyzed for
      both LOH and microsatellite instability with 34 markers at or linked to hMLH1
      (3p21), hMSH2 (2p16), hMSH3 (5q11-q13), hMSH6 (2p16), hPMS1 (2q32), and hPMS2
      (7p22) loci. Chromosomal regions 3p21 and 5q11-q13 were found to be hemizygously
      deleted in 55% and 42% of the patients, respectively. Sixty five percent of the
      patients deleted at hMLH1 were also deleted at hMSH3. The shortest regions of
      overlap for 3p21 and 5q11-q13 deletions delimited by D3S1561/D3S1612 and
      D5S2107/D5S624, respectively, were restricted to genetic distances of only 1 cM.
      Currently, the hMLH1 (3p21) and hMSH3 (5q11-q13) genes are the only known
      candidates located within these regions. The mutational analysis of hMLH1 and
      hMSH3 in hemizygously deleted patients led to the detection of 2 new
      polymorphisms in hMSH3. The consequence of these allelic losses remains unclear,
      but the lack of inactivating mutation might explain that replication error, the
      hallmark of mismatch repair genes inactivation in cancer cells, was quasi-absent
      in tumors. We suggest that hMLH1 and hMSH3 genes could be involved in lung
      tumorigenesis through dosage effect in cellular functions other than replication
      error correction.

PMID- 9650549
TI  - Chimeric scFv/gamma receptor-mediated T-cell lysis of tumor cells is coregulated
      by adhesion and accessory molecules.
AB  - Adhesion and accessory molecules play a critical role in T-cell activation and
      effector function in general and in tumor cell recognition and lysis in
      particular. We investigated the contribution of CD2, CD3, CD11a/CD18, CD54 and
      CD58 molecules in T lymphocyte-tumor cell interactions mediated by chimeric
      immunoglobulin receptors. The chimeric receptor is composed of a single chain
      antibody binding site and a gamma-chain signal transducing molecule (scFv/gamma).
      T lymphocytes expressing such scFv/gamma receptors recognize the G250 Ag on renal
      cell carcinoma (RCC) in an major histocompatibility complex (MHC)-unrestricted
      manner and exert RCC selective cytolysis. A coregulatory role for CD2, CD3 and
      CD11a/CD18 molecules in scFv/gamma-mediated cytolysis was demonstrated using
      monoclonal antibody (MAb)-induced inhibition of scFv/gamma-mediated cytolysis.
      The inhibition of lysis was not due to inhibition of cytotoxic T lymphocyte (CTL)
      target cell conjugation but rather to a post-conjugate signaling event. Binding
      of CD54 and CD58 MAbs to the RCC did not inhibit cytolysis of RCC cells that
      expressed high levels of both CD54 and the G250 antigen (Ag) (A75), whereas
      cytolysis of RCC expressing intermediate levels of CD54 and G250 Ag (SK-RC-17
      cl.4) was partly inhibited by the CD54 MAb. Binding of low concentrations of G250
      MAb to RCC (A75) rendered these cells sensitive to CD54 MAb inhibition,
      demonstrating a direct functional relation between G250 Ag expression level and
      adhesion molecules. Taken together, our findings indicate a coregulatory role for
      CD2, CD3 and CD11a/CD18 molecules in the scFv/gamma-mediated cytolysis of tumor
      cells and show that the requirement of CD11a/CD18-CD54 interactions is dependent
      on the level of free Ag. This make these gene-transduced T lymphocytes attractive
      tools for adoptive immunogene therapy of cancer.

PMID- 9650550
TI  - Predictors of level of circulating abnormal lymphocytes among human T
      lymphotropic virus type I carriers in Japan.
AB  - Human T-lymphotropic virus type I (HTLV-I) carriers often have abnormal
      lymphocytes (Ably) that resemble malignant cells of adult T-cell leukemia (ATL).
      To identify predictors of the level of Ably in a longitudinal study of
      asymptomatic HTLV-I carriers, we analyzed data from 215 subjects (67 men and 148
      women) with multiple Ably measurements on blood smears. Ably+ (those having Ably
      > 0.6% of leukocytes counted on a blood smear at least once) was strongly
      associated with a high proviral load (OR 8.9; 95% CI 4.1, 19.5). The association
      among those defined as Ably++ (Ably > 0.6% at all screens or Ably > 1.6% at least
      once) was higher (19.7; 6.9, 56.1). Ably++ was also significantly associated with
      male gender (2.8; 1.0, 7.8). Multivariate analysis of Ably level indicates that
      men with a high proviral load, high anti-HTLV-I titer and low anti-Tax reactivity
      have the highest Ably level.

PMID- 9650551
TI  - MUC6 expression in breast tissues and cultured cells: abnormal expression in
      tumors and regulation by steroid hormones.
AB  - Neoplastic transformation of epithelial cells is commonly associated with
      alterations in the expression of mucin genes. The mechanisms involved in this
      process are largely unknown. MUC6, isolated from a stomach cDNA library, is
      mainly expressed in stomach antral glands, as detected by using in situ
      hybridization and immunohistochemistry. We examined MUC6 expression in normal and
      pathological breast tissues using immunohistochemistry with MUC6-specific
      antibodies and in cultured breast cancer cells using immunocytochemistry and
      Northern blotting. MUC6 was generally not detected in normal breast (1/11) but
      was detected in fibrocystic disease without atypia (7/17, 41%), in atypical
      fibrocystic disease (11/11, 100%) and in carcinoma (57/60, 95%). To study the
      mechanisms involved in mucin gene up-regulation in breast cancer, we examined
      baseline, growth-related and steroid-induced levels of MUC1, MUC3 and MUC6 in 4
      breast cancer cell lines, 2 of which express estrogen receptors. MUC6 levels were
      up-regulated at post-confluence in 2/4 cell lines, whereas no changes were
      detected for the other mucin genes examined. MUC6 and MUC3 were constitutively
      expressed, and steroid-induced, in BT-474 and MCF-7 cells, respectively. As a
      control, pS2 was induced in both cell lines. Our results indicate that (1) MUC6
      is overexpressed in breast cancer and in benign breast disease, (2) in vitro,
      MUC6 and MUC3 are up-regulated by steroids and (3) abnormal expression of MUC6 in
      breast cancers may, in part, be explained by hormonal changes associated with
      tumor development.

PMID- 9650552
TI  - High homogeneity of MAGE, BAGE, GAGE, tyrosinase and Melan-A/MART-1 gene
      expression in clusters of multiple simultaneous metastases of human melanoma:
      implications for protocol design of therapeutic antigen-specific vaccination
      strategies.
AB  - Human melanoma cells express several antigens which are recognized by autologous
      and specific CTL clones in association with HLA-class-I molecules. Many of these
      antigens represent suitable targets for tumor immunotherapy, since their
      expression in human melanoma cells is common and highly specific. In order to
      achieve real clinical success with therapeutic vaccination strategies, one
      important requirement is the expression of the target antigen by all the tumor
      lesions of a patient. We have studied this issue by assessing, through an RT-PCR
      approach, the expression of MAGE-1, MAGE-2, MAGE-3, BAGE, GAGE-1/2, Tyrosinase
      and Melan-A/MART-1 genes in 17 clusters of simultaneous in-transit or regional
      lymph-node metastases collected from 15 stage-III and 1 stage-IV (AJCC/UICC pTNM
      system) melanoma patients. In 14 out of 17 clusters of simultaneous metastatic
      lesions (82%), the homogeneity in the pattern of gene expression within the
      cluster was complete. Heterogeneity within the same cluster was observed in only
      3 out of 17 clusters (18%) and represented only minor features. Our data reveal
      that, in AJCC-stage-III melanoma patients, different but simultaneous metastatic
      lesions express the same pattern of antigen-coding genes. These observations have
      2 main clinical implications: (i) the antigenic characterization of one single
      and easily accessible lesion allows identification of optimal targets for an
      active antigen-specific immunotherapy treatment; (ii) almost all the metastatic
      lesions are expected to be hit by the immune response eventually induced against
      the tumor antigen. Moreover, these data suggest that active specific
      immunotherapy directed against MAGE-1, MAGE-3, BAGE, GAGE-1/2, Melan-A/MART-1 and
      Tyrosinase antigens could be exploited as an adjuvant treatment to surgery in
      high-risk AJCC-stage-III-melanoma patients.

PMID- 9650553
TI  - Different distribution of H1-H2 Epstein-Barr virus variant in oropharyngeal virus
      and in biopsies of Hodgkin's disease and in nasopharyngeal carcinoma from
      Algeria.
AB  - In a previous study of Epstein-Barr virus (EBV) strains in North African
      nasopharyngeal carcinoma (N PC) biopsies, we have found that the viral strain
      present was of A/F/W'-I'/Xhol kept/H1-H2 type, while the strain associated with
      Chinese NPC was the A/"f"/W'I'/Xhol lost/H type. Using the restriction fragment
      length polymorphism (RFLP) and PCR-RFLP methods, the present study analyzed the
      H1-H2 variant in different clinical samples from Algeria, including the saliva of
      healthy EBV-positive individuals and patients with NPC or Hodgkin's disease (HD),
      as well as HD biopsies and lymphoblastoid cell lines (LCLs) established from the
      oropharyngeal virus-infected cells. Our results demonstrate that, in contrast to
      the H1-H2 variant found in NPC biopsies, the H genotype was dominant in HD
      biopsies. Moreover, H genotype was also dominant in the oropharynx of healthy EBV
      positive individuals, of patients with NPC and with HD. Our results clearly
      indicate that in North Africa the EBV strain present of NPC biopsies is different
      from that shed in the oropharynx. This may suggest a specific distribution of the
      H1-H2 variant in the NPC epithelial tumor, whereas the H genotype is dominant in
      HD biopsies and in the oropharynx. The specific association of both viral strains
      with these 2 distinct diseases in North Africa may reflect a difference in
      tumorigenicity.

PMID- 9650554
TI  - Cruciferous vegetables in relation to renal cell carcinoma.
AB  - Little is known about the possible role of diet in the development of renal cell
      carcinoma (RCC). A population-based case-control study was conducted in non
      Asians of Los Angeles; it included 1,204 RCC patients and an equal number of
      neighborhood controls matched to the index cases by sex, date of birth (within 5
      years) and ethnicity. Information on intake frequencies of food groups rich in
      vitamins A and C, various carotenoids and nitrosamines or their precursors was
      collected through in-person, structured interviews. After adjustment for non
      dietary risk factors including level of education, obesity, history of
      hypertension, cigarette smoking and regular use of analgesics and amphetamines,
      there were strong inverse associations between cruciferous and dark green
      vegetable intakes and RCC risk (both p values for linear trend < 0.001). In terms
      of nutrients, there were significant inverse associations of RCC risk with
      consumption of a variety of carotenoids including alpha-carotene (p < 0.001),
      beta-carotene (p = 0.004), beta-cryptoxanthin (p = 0.01) and lutein (p = 0.005).
      However, after adjustment for these nutrients, we still observed a significant
      residual effect of cruciferous vegetables, suggesting that other substances
      present in these vegetables may be responsible, at least partially, for the
      observed reduction in risk of RCC. Dietary nitrosamines and their precursors were
      not related to RCC risk.

PMID- 9650555
TI  - Cytogenetics of a malignant ovarian germ-cell tumor.
AB  - Cytogenetic investigation of a malignant ovarian tumor diagnosed as a mixed germ
      cell tumor, composed of extensive choriocarcinoma and foci of yolk-sac tumor,
      revealed a highly abnormal chromosomal pattern. We found a chromosome number in
      the hypertriploid/hypotetraploid range, and several clonal structural
      abnormalities, including 2 copies of an isochromosome 12p. We showed that the
      chromosomal pattern of this ovarian tumor is very similar to that of testicular
      germ-cell tumors. This finding, together with reported cytogenetic data of
      malignant ovarian germ-cell tumors, supports the hypothesis that ovarian and
      testicular germ-cell tumors are strongly related entities that may have a similar
      origin and pathogenetic pathway.

PMID- 9650556
TI  - Oral contraceptives and breast cancer risk in Taiwan, a country of low incidence
      of breast cancer and low use of oral contraceptives.
AB  - One hundred and seventy four (81% of all) pathologically confirmed new incident
      cases of female breast cancer identified from a medical center in Taipei from
      February, 1993 to June, 1994 were selected as the case group. Four hundred and
      fifty three inpatient controls who were without obstetric-gynecological, breast,
      or malignant diseases were individually matched for each case by age and date of
      admission. Information was obtained through direct interview and review of
      medical records. Conditional logistic regression was used to estimate the effects
      of each risk factor. After adjusting for education level, body mass index, age at
      menarche and first full-term pregnancy, parity, menopausal status and age at
      menopause, lifetime lactation, use of lactation inhibition hormones, and family
      history of breast cancer, breast cancer risk significantly elevated in use of OC
      before 25 years old and before 1971. In stratified analysis, significantly higher
      risk were found in OC use before 25 years old and in duration of use less than
      one year among post-menopausal subjects. Our results support the notion that OC
      use in early life for younger women and in early calendar years increase breast
      cancer risk.

PMID- 9650557
TI  - Parity and the risk of pancreatic cancer: a nested case-control study.
AB  - Smoking is the only generally accepted risk factor for pancreatic cancer.
      Reproductive history has in recent studies been associated with pancreatic
      cancer, but with contradictory results. In order to evaluate a possible
      association between age at first birth and the number of births and pancreatic
      cancer, we conducted a nested case-control study by linking 2 Swedish nationwide
      registries: the Cancer Registry and The Fertility Registry. Among women born
      between 1925 and 1970, 1,015 patients with pancreatic cancer were compared with
      5,073 age-matched controls. No association between pancreatic cancer and number
      of births was found. Age at first birth was inversely related with the risk of
      pancreatic cancer (OR per 5 years = 0.90; 95% CI 0.83-0.97; p = 0.01), an
      association mainly confined to women with a diagnosis of pancreatic cancer before
      50 years of age (OR per 5 years = 0.85; 95% CI 0.73-1.00; p = 0.04). This trend
      remained after adjustment for parity, but was less prominent. Young age at first
      birth and high parity in Sweden are, however, associated with an increased
      frequency of smoking, thus at least some of the increased risk for pancreatic
      cancer in women with young age at first birth is likely to be explained by
      smoking acting as a confounder.

PMID- 9650558
TI  - Nasopharyngeal carcinoma in Malaysian Chinese: salted fish and other dietary
      exposures.
AB  - We interviewed 282 histologically confirmed cases of nasopharyngeal carcinoma
      (NPC) in Chinese residents of Selangor and the Federal Territory, Malaysia, and
      an equal number of Chinese age-, sex-, and length-of-residence-matched controls
      sampled from the general population. Consumption of 55 dietary items during
      childhood, and 5 years pre-diagnosis of NPC, was analyzed by univariate and
      multivariate methods. Four salted preserved foods (fish, leafy vegetables, egg
      and root), fresh pork/beef organ meats and beer and liquor consumption exhibited
      strong positive associations, and 4 vegetable/fruit combinations strong negative
      associations with NPC. Factor analysis and multivariable modeling using estimated
      factor scores strongly supported separate effects on NPC of vegetables/fruits,
      salted preserved foods, pork/beef organ meats and beer/liquor consumption.
      Multivariable modeling associated NPC most clearly with high consumption of
      salted fish, salted eggs, pork/beef liver and beer and low consumption of Chinese
      flowering cabbage, oranges/tangerines and shrimp. A strong residual association
      of social class with NPC remained after adjustment for diet, which is consistent
      with a substantial role for non-dietary environmental factors.

PMID- 9650559
TI  - Complexes between urokinase-type plasminogen activator and its receptor in blood
      as determined by enzyme-linked immunosorbent assay.
AB  - Complexes between urokinase-type plasminogen activator (uPA) and its receptor
      (uPAR) were assessed in plasma and serum from 39 breast cancer patients and from
      20 healthy individuals, applying a recently developed enzyme-linked immunosorbent
      assay (ELISA) for the analysis of these complexes in tumor tissue extracts. The
      assay is based on a combination of rabbit polyclonal anti-uPA antibodies for
      catching and a mouse anti-uPAR monoclonal antibody (MAb) for detection. The
      specificity of the assessment of uPA:uPAR complexes was verified by simultaneous
      analysis of the individual blood samples in corresponding non-sense ELISA
      formats, in which either the anti-uPA catching antibody or the anti-uPAR
      detecting antibody was substituted with an irrelevant antibody. Assessment of
      native uPA:uPAR complexes was ascertained by demonstrating the absence of any de
      novo formation of uPA:uPAR complexes in plasma and serum during the sample
      incubation step in the ELISA, as verified by the use of a peptide antagonist for
      uPAR. Plasma and serum samples contained almost identical levels of uPA:uPAR
      complexes. The levels of uPA:uPAR complexes were found to be significantly lower
      in serum from breast cancer patients compared to the serum of healthy donors,
      while the levels of (total) uPAR in plasma from breast cancer patients were
      significantly higher than in plasma from the healthy controls. In addition, the
      free, uncomplexed uPAR levels, estimated by subtraction of uPA:uPAR complex
      levels from (total) uPAR levels, were significantly elevated in plasma as well as
      in serum from breast cancer patients compared to healthy individuals. The
      uPA:uPAR complex levels were highly comparable to the uPA levels analyzed in the
      same plasma and serum samples, indicating that most if not all of the uPA present
      in these samples is complexed with uPAR.

PMID- 9650560
TI  - Mechanism of antitumor action of PKC activator, gnidimacrin.
AB  - Daphnane-type diterpene gnidimacrin isolated from the Chinese plant Stellera
      chamaejasme L. is an antitumor agent that activates protein kinase C (PKC). The
      mechanism of antitumor action of gnidimacrin and the possible involvement of PKC
      were examined using sensitive K562 and refractory HLE cells. Gnidimacrin did bind
      to K562 cells 3 times more than to HLE cells. Immunoblot analyses revealed
      pronounced PKC betaII expression in gnidimacrin sensitive cell lines including
      K562 cells, while refractory HLE cells strongly expressed PKC alpha, but not PKC
      betaII. In a 24-hr exposure of K562 cells to gnidimacrin, G1 phase arrest and
      inhibition of cdk2 kinase activity was found at growth-inhibitory concentration
      (0.0005 microg/ml). Complete inhibition of cdk2 activity and maximum G1 phase
      arrest were observed at 0.005 microg/ml, however, these biological effects were
      reduced at 0.05 microg/ml (260 times the 50% inhibitory concentration). Cellular
      PKC after a 24-hr exposure was examined by immunoblot analysis and specific
      binding of [3H]phorbol-12,13-dibutyrate as a ligand of PKC. Expression and the
      amount of functional PKC of K562 cells were not changed at 0.002 microg/ml, but
      down-regulated to less than 1/10th of the control at 0.05 microg/ml. The
      reduction of biological effects at 0.05 microg/ml is most likely due to PKC down
      regulation. Our results suggest that PKC (particularly betaII) is one of the
      major determinants of the ability of cells to respond to gnidimacrin and that the
      antitumor action might be associated with cell-cycle regulation through
      suppression of cdk2 activity.

PMID- 9650561
TI  - Anti-CD3-based bispecific antibody designed for therapy of human B-cell
      malignancy can induce T-cell activation by antigen-dependent and antigen
      independent mechanisms.
AB  - Anti-CD3 x anti-B-cell antigen bispecific monoclonal antibodies (bsAbs) can
      redirect T-cell-mediated lysis toward malignant B cells. Clinical trials with CD3
      based bsAbs have shown toxicity in patients which is likely related to
      nonspecific T-cell activation and targeting. Our current studies were designed to
      explore the mechanisms responsible for the observed in vivo toxicity by
      evaluating the immunologic effects of 2 different bsAb preparations in vitro.
      1D10 was used as the tumor specific arm of the bsAbs. This antibody reacts with a
      variant of HLA-DR found on a majority of pre-B- and B-cell malignancies, and
      normal B cells in some individuals. Anti-CD3 served as the T-cell specific arm. A
      1D10 x anti-CD3 bispecific IgG (bsIgG) produced using the hybrid-hybridoma method
      was compared to a 1D10 x anti-CD3 bispecific F(ab')2 [bsF(ab')2] produced using
      the leucine zipper technique. In cytotoxicity assays, both bsIgG and bsF(ab')2
      induced lysis by pre-activated T cells of 1D10 (+) malignant B cells. bsIgG at
      high concentrations also induced lysis of 1D10 (-) tumor cells, while bsF(ab')2
      did not. Proliferation of T cells induced by bsIgG and bsF(ab')2 was also
      evaluated. Both forms of bsAbs induced T-cell proliferation in the presence of
      antigen (+) Raji cells, while only bsIgG did so in the presence of antigen (-)
      malignant B cells. bsF(ab')2 induced T-cell activation in the absence of any
      tumor cells when testing was performed on samples where the 1D10 target antigen
      was present on normal peripheral blood B cells. We conclude that non-specific T
      cell activation from bsAbs can occur in an antigen-independent manner due to the
      Fc/Fc receptor (FcR) interaction, or in an antigen-dependent manner when antigen
      is expressed on normal or tumor cells. Both mechanisms may have been responsible
      for the toxicity observed in prior clinical studies.

PMID- 9650562
TI  - Over-expression of urokinase receptor in human epidermoid-carcinoma cell line
      (HEp3) increases tumorigenicity on chorio-allantoic membrane and in severe
      combined-immunodeficient mice.
AB  - Using chorio-allantoic membranes (CAMs) of chick embryos and severe-combined
      immunodeficient (SCID) mice, we investigated the effects of urokinase-type
      plasminogen-activator receptor (u-PAR) over-expression on the process of invasion
      and tumorigenicity. By the transfection of u-PAR cDNA, 3 u-PAR-over-expressing
      clones expressing 1.6- to 4.6-fold more u-PAR mRNA than parent cells were
      obtained from a human epidermoid-carcinoma cell line, HEp3, that expresses
      urokinase-type plasminogen activator (u-PA) and u-PAR. All the u-PAR-over
      expressing clones showed greater invasiveness (13 to 29%) than that of parent
      HEp3 cells on CAMs. Immunohistochemistry revealed densely stained u-PAR-positive
      cells near the margin of the tumor, where a u-PAR-over-expressing clone,
      designated SM-3, was invading thickened fibrous tissue on CAMs. Three u-PAR
      overexpressing clones formed larger tumors (>40 mm3) than did parent HEp3 cells
      on CAMs. Moreover, when the u-PAR-overexpressing clone (SM-3) was injected s.c.
      into the back of the SCID mice it produced a larger tumor volume than the control
      (HEp3) and down-regulated (AS-2) clones and significantly shortened the survival
      of SCID mice. These results demonstrate that increased u-PAR expression is an
      important factor in determining the malignant phenotype that makes cancer cells
      more invasive and tumorigenic.

PMID- 9650563
TI  - SP220K is a novel matrix serine proteinase.
AB  - Matrix proteinases play a critical role in extracellular matrix remodeling, which
      is particularly involved in cancer invasion and metastasis. We have previously
      characterized and purified a new tetrameric serine proteinase (SP220K) from human
      kidney clear cell carcinoma plasma membranes. Here, we report that SP220K
      exhibits gelatinase activity as assessed both in solution and by zymography.
      Optimum gelatinase activity ranges between pH 7.5 to pH 9.0. Fibronectin and type
      I collagen were hydrolyzed by SP220K, at variance with laminin and type IV
      collagen. Like other trypsin-like fibronectin degrading proteinases, SP220K
      released the 29-kDa N-terminal heparin-binding domain of fibronectin. By using a
      panel of proteinase inhibitors, we found that the inhibition profile of SP220K
      was different from that of other known serine proteinases such as thrombin,
      trypsin, plasmin, plasminogen activators and tryptase. Altogether, our results
      indicate that SP220K corresponds to a novel matrix proteinase that exhibits a
      marked specificity for fibronectin and type I collagen.

PMID- 9650564
TI  - 12(S)-hydroxyeicosatetraenoic acid increases the actin microfilament content in
      B16a melanoma cells: a protein kinase-dependent process.
AB  - 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE], a lipoxygenase metabolite of
      arachidonic acid, has been shown to be involved in a wide variety of cellular
      activities (i.e., adhesion, spreading, motility, invasion) which promote
      metastasis to occur in tumor cells. In this study, several techniques (Western
      blotting, flow cytometry and DNase I assay) were performed to examine the
      alterations in the distribution of G- and F-actin expressed in B16a melanoma
      cells. Each of these methods independently revealed that 12(S)-HETE treatment
      (0.1 mM, 15 min) resulted in an increase in the F-actin content in the
      cytoskeletal preparations. Since the integrity of cytoskeletal networks (i.e.,
      actin filaments) can be dynamically regulated through protein phosphorylation, we
      investigated the potential role of several protein kinases in the 12(S)-HETE
      induced actin polymerization. By flow cytometric analysis, 12(S)-HETE was found
      to increase the actin filament contents. This effect could be inhibited by
      protein kinase C (PKC) inhibitors (calphostin C and staurosporine) as well as by
      protein tyrosine kinase (PTK) inhibitor (genistein) but not by protein kinase A
      inhibitor (H8), suggesting that the 12(S)-HETE effect involves PKC and PTK. This
      conclusion is consistent with the observations that phorbol 12-myristate-13
      acetate (PMA) mimics the biological effect of 12(S)-HETE in promoting the F-actin
      formation in B16a cells. As a final analysis, direct protein phosphorylation
      studies indicate that 12(S)-HETE treatment led to enhanced phosphorylation of
      myosin light chain, which may contribute to the increased stress fiber formation
      following 12(S)-HETE stimulation.

PMID- 9650565
TI  - Effect of a newly developed bisphosphonate, YH529, on osteolytic bone metastases
      in nude mice.
AB  - YH529, [1-hydroxy-2-(imidazo [1,2-a] pyridin-3-yl) ethylidene]-bisphosphonic acid
      monohydrate, is a newly developed third-generation bisphosphonate with a potent
      inhibitory activity toward osteoclastic bone resorption. The primary cellular
      mechanism of osteolysis associated with metastatic cancer is osteoclast-mediated.
      It is likely that bisphosphonates would be efficacious in this situation. In the
      present study, we examined the effect of YH529 in a nude mice bone metastasis
      model, in which the intracardiac injection of a human breast cancer cell line,
      MDA-MB-231 (MDA-231), leads to osteolytic bone metastases. To examine whether
      YH529 would prevent such bone metastasis, we administered YH529 s.c. to nude mice
      simultaneously with cancer cell inoculation through the entire experimental
      period (protocol 1) or performed short-term prophylactic administration before
      inoculation of the MDA-231 cells (protocol 2). In addition, to examine the
      possible therapeutic effects of the drug on established bone metastases, we
      injected YH529 after radiographically small but distinct osteolytic bone
      metastases had been detected (protocol 3). In all protocols, YH529 (2
      microg/mouse/day) markedly inhibited bone metastases as well as the progression
      of established metastatic foci that were quantified on the radiographs.
      Histological examination and histomorphometrical analysis revealed that YH529
      markedly reduced the number of osteoclasts and the size of the tumor at the
      metastatic bone sites. Our results suggest that YH529 may suppress metastasis
      formation and tumor growth in bone through inhibition of osteoclastic bone
      resorption.

PMID- 9650566
TI  - Fasting/re-feeding before initiation enhances the growth of aberrant crypt foci
      induced by azoxymethane in rat colon and rectum.
AB  - In contrast to the protective effect of chronic caloric restriction on tumor
      development, we have shown that fasting sustained tumor initiation in rat liver
      by a noninitiating dose of diethylnitrosamine. Here we investigated whether
      fasting had a similar favorable effect on initiation in the colorectal mucosa in
      80 male F344 rats. Animals fasted for 4 days were given a single s.c. dose of
      azoxymethane (AOM) (20 mg/kg) on the first day of re-feeding, and rates of
      kinetic proliferative parameters, and development of the pre-neoplastic lesions
      such as aberrant crypt foci (ACF), were evaluated. Starvation before AOM
      treatment enhanced the growth of ACF, as shown by the significantly higher crypt
      multiplicity of fasted/re-fed rats as compared with fully fed rats (3.97 +/- 0.50
      vs. 2.64 +/- 0.20, p < or = 0.025). This difference was associated with
      perturbations in cell death and cell proliferation. Fasting induced apoptosis and
      depressed cell division, while re-feeding had opposite effects, resulting in a
      higher percentage of S-phase cells at the time of AOM injection and 2 days
      thereafter. Starvation-induced apoptosis may represent the mitogenic stimulus to
      an increase in the number of cells susceptible to AOM damage, and may favor its
      fixation, leading to enhanced growth of ACF. Our data therefore suggest that
      fasting/re-feeding enhances colon cancer.

PMID- 9650567
TI  - Extracellular matrix modulates expression of growth factors and growth-factor
      receptors in liver-colonizing colon-cancer cell lines.
AB  - Site-specific metastasis is determined by the extracellular matrix (ECM) of the
      colonized organ. We have shown that hepatocyte-derived ECM stimulated
      proliferation of colon-cancer cells via induction of autocrine growth factors and
      their receptors. The ECM component responsible was heparin proteoglycan. We
      therefore investigated the effect of exogenously added heparin on colon cell
      lines of varying liver-colonizing potential. The cells were grown on typical
      liver matrix components, such as fibronectin and collagens type I and IV. We
      assessed the effect of these matrix components on clonal growth, proliferation
      and expression of autocrine growth factors and their receptors. The clonal growth
      of the KM12 cells was not affected by heparin, while the other cell lines were
      inhibited by heparin. Cell proliferation in weakly metastatic KM12, but not in
      strongly metastatic KM12SM, was inhibited by heparin on plastic. Weakly
      metastatic LS174T, but not strongly metastatic LiM6, was inhibited by heparin on
      fibronectin. Expression of erb-B2 was also differently modulated by heparin in
      weakly metastatic vs. highly metastatic cells. In weakly metastatic cells,
      heparin reduced erb-B2 levels when cells were on plastic and fibronectin, while
      in strongly metastatic cells, erb-B2 was induced by heparin. In all 4 cell lines,
      mRNA for cripto was induced by heparin when the cells were grown on fibronectin.
      In KM12SM cells, amphiregulin was induced by heparin in cells on fibronectin and
      collagen IV. We show that soluble heparin, similar in its carbohydrate chemistry
      to liver heparin proteoglycan, regulates the growth of colon-cancer cells. This
      effect depends on other matrix components found in the liver and is mediated in
      part by EGF family members.

PMID- 9650568
TI  - Chemoprevention by N-acetylcysteine of urethane-induced clastogenicity and lung
      tumors in mice.
AB  - A major goal in pre-clinical cancer chemoprevention research is to assess the
      predictive value of intermediate biomarker modulation towards tumor prevention.
      With this aim, BALB/c mice were treated with 10 daily i.p. injections of urethane
      (ethyl carbamate), each of 400 mg/kg body weight. Groups of mice received with
      drinking water either a drug containing the thiol N-acetylcysteine (NAC), at 0.1
      or 0.5 g/kg body weight, or its excipient, starting 27 days before the first
      injection of the carcinogen until the end of the experiment. Out of the 30 mice,
      10 per group were identified and individually monitored for 8 sequential times in
      order to assess the course of micronucleated normochromatic erythrocytes in
      peripheral blood. This systemic genotoxicity biomarker increased during the 10
      day period of treatment with urethane, reached a peak 2 to 6 days after the last
      injection, and was still significantly higher than the baseline after 10
      additional days. Clastogenicity was significantly inhibited by NAC, with a dose
      related effect, but not by the drug excipient. As evaluated 4 months after the
      first injection of urethane, most mice developed lung tumors, whose multiplicity
      was not affected by the drug excipient but was significantly decreased in the
      presence of NAC. Correlation between the frequency of micronucleated
      normochromatic erythrocytes at peak levels and lung-tumor multiplicity was highly
      significant when evaluated in the context of all 40 mice undergoing cytogenetic
      analyses (r = 0.561, p = 0.0002). It was similarly high, but did not reach the
      significance threshold, within each treatment group, due to the lower number of
      animals and some deviations from the regression line. Therefore, the prediction
      of lung-tumor yield based on the intensity of the early genotoxicity biomarker is
      justified when formulated within a sufficiently large group of animals, but is
      not absolute at individual level.

PMID- 9650569
TI  - Expression of Ly-6, a marker for highly malignant murine tumor cells, is
      regulated by growth conditions and stress.
AB  - Ly-6E.1 is highly expressed in murine tumor cells with a high malignancy
      phenotype and may serve as a marker for such a phenotype. In this study, we
      examined the effects of various growth conditions and stress on the expression
      levels of Ly-6E.1 by tumor cells. Previous preliminary results have shown that
      murine DA3 mammary tumor cells expressing high levels of Ly-6E.1 (Ly-6(hi)) are
      more highly tumorigenic than the same tumor cells expressing low levels of this
      membrane protein (Ly-6(lo)). In this study, we demonstrate that mice bearing Ly
      6(hi) DA3 tumors have a significantly higher burden of spontaneous pulmonary
      metastasis than mice bearing Ly-6(lo) DA3 tumors. Furthermore, the survival time
      of the former mice was significantly shorter than that of the latter ones. We
      further show that certain other members of the Ly-6 gene family such as Ly-6C.1
      and Ly-6G.1 are coregulated with Ly-6E.1. This was shown to occur with respect to
      both DA3 cells as well as A3 tumor cells which are of fibroblast origin. However,
      these 2 cells differ with respect to regulation of Sca-2 (TSA1, another member of
      the Ly-6 family) expression on these cells. Levels of Sca-2 on A3 cells appear to
      be coregulated with Ly-6E.1 (i.e., Ly-6(hi) A3 cells express high levels of Sca-2
      and Ly-6(lo) A3 cells express low levels of Sca-2). These 2 Ly-6 proteins were,
      however, not coregulated on DA3 cells. Both Ly-6(hi) as well as Ly-6(lo) DA3
      cells express equal levels of Sca-2. Levels of Thy-1, another
      glycosylphosphatidylinositol (GPI)-anchored protein expressed by A3 tumor cells,
      were equally expressed by both Ly-6(hi) and Ly-6(lo) A3 tumor cells. Levels of Ly
      6 (but not those of CD44) on A3 tumor cells were upregulated on cells from dense
      cultures but were not influenced by the position of the cells in the cell cycle.
      Stress conditions such as serum starvation or heat shock upregulated the
      expression of Ly-6 by the 2 types of tumor cells but did not induce apoptosis in
      these cells. The kinetics of the stress-dependent upregulation of Ly-6 expression
      differed, however, between the epithelial and fibroblastic tumor cells.

PMID- 9650570
TI  - Prevalence of respiratory symptoms and increased specific IgE levels in West
      African workers exposed to isocyanates.
AB  - Respiratory symptoms and immunological effects from chronic exposure to
      isocyanates (toluene diisocyanate) were studied in a cross survey of workers from
      West African factories producing paints and polyurethane foam. A questionnaire, a
      pulmonary function test, immunoglobulin E (IgE) levels, radioallergosorbent test
      (RAST) and an atmospheric sample to quantify isocyanate exposures were carried
      out in the workplace for each worker. Ninety-six workers, of whom 44 had
      occupational isocyanate-induced asthma, were included in the study. Twenty-four
      viral-infected subjects were excluded from the immunological study. Specific
      antibodies to isocyanates were detected in two of the symptomatic individuals.
      This low proportion appeared to be a common feature of this disease. The
      prevalence of isocyanate-induced asthma in a West African working population
      appears to be significant in the context of chronic human exposure, as current
      data are based on excessive acute exposure due to an accident as seen in India.

PMID- 9650571
TI  - Multigenerational study of the effects of consumption of PCB-contaminated carp
      from Saginaw Bay, Lake Huron, on mink. 1. Effects on mink reproduction, kit
      growth and survival, and selected biological parameters.
AB  - This study was conducted to determine the multigenerational effects of
      consumption of PCB-contaminated carp (Cyprinus carpio) from Saginaw Bay (Lake
      Huron) on mink (Mustela vison) reproduction and health and to examine selected
      biomarkers as potential indicators of polyhalogenated hydrocarbon toxicity in
      mink. The mink were fed diets formulated to provide 0 (control), 0.25, 0.5, or
      1.0 ppm polychlorinated biphenyls (PCBs) through substitution of Saginaw Bay carp
      for ocean fish in the diets. To determine whether the effects of PCB exposure
      were permanent, half of the parental (P1) animals were switched from their
      respective treatment diets to the control diet after whelping the first of two F1
      generations. Effects of in utero and lactational exposure to PCBs on subsequent
      reproductive performance of the F1 animals were examined by switching half of the
      first-year F1 offspring (kits) to the control diet at weaning, while the other
      half was continued on their parental diet (continuous exposure). Continuous
      exposure to 0.25 ppm, or more, of PCBs delayed the onset of estrus (as determined
      by vulvar swelling and time of mating) and lessened the whelping rate. Litters
      whelped by females continually exposed to 0.5 ppm, or more, of PCBs had greater
      mortality and lesser body weights than controls. Continuous exposure to 1.0 ppm
      PCBs had a variable effect on serum T4 and T3 concentrations. Compared to the
      controls, there were significant differences in kidney, liver, brain, spleen,
      heart, and thyroid gland weights of the mink continually exposed to 1.0 ppm PCBs.
      There was an increase in the incidence of periportal and diffuse vacuolar
      hepatocellular lipidosis in the P1 mink with continuous exposure to increasing
      concentrations of PCBs. Plasma and liver PCB concentrations of the adult and kit
      mink were, in general, directly related to the dietary concentration of PCBs and
      the duration and time of exposure. Short-term parental exposure to PCBs had
      detrimental effects on survival of subsequent generations of mink conceived
      months after the parents were placed on "clean" feed. The lowest observed adverse
      effect level (LOAEL) for dietary PCBs in this study was 0.25 ppm.

PMID- 9650572
TI  - Multigenerational study of the effects of consumption of PCB-contaminated carp
      from Saginaw Bay, Lake Huron, on mink. 2. Liver PCB concentration and induction
      of hepatic cytochrome P-450 activity as a potential biomarker for PCB exposure.
AB  - This study examined the effect of polychlorinated biphenyls (PCBs) from Saginaw
      Bay (Lake Huron) carp on the hepatic cytochrome P-450 activity in mink (Mustela
      vison). Hepatic cytochrome P-450 activities are of interest for their possible
      use as biomarkers to indicate consumption and biological effects of PCBs in the
      environment. Adult mink were fed diets containing ocean fish (control diet, 0.0
      ppm) or Saginaw Bay carp toprovide 0.25, 0.5, or 1.0 ppm PCBs. Mink were bred
      after 3 mo of exposure, and half of the parental mink (P1) and kits (F1-1)
      previously consuming diets containing Saginaw Bay carp were switched to control
      diet at weaning of the F1-1 kits. P1 and F1-1 mink were then bred within their
      age and dietary groups after 15 mo of exposure, to produce the second-year F1 (F1
      2) and F2 kits. Mink were killed when the new kits were weaned. Transfer of half
      the animals to the control diet examined whether the effects of the PCB
      containing diet on hepatic cytochrome P-450 activity were permanent. Continual
      exposure to diets containing PCBs from Saginaw Bay carp induced cytochrome P-450
      activity in a generally dose-dependent manner. Cytochrome P-450 activity was not
      different from untreated controls in animals switched to the control diet from
      the PCB-containing diet. The response of cytochrome P-4501A1 (EROD) activity in a
      dose-dependent manner and the lack of induction after transfer to noncontaminated
      diets suggest that this hepatic enzyme activity is a potential biomarker for
      current exposure to PCBs and other similar cytochrome P-450 inducers.

PMID- 9650573
TI  - Multigenerational study of the effects of consumption of PCB-contaminated carp
      from Saginaw Bay, Lake Huron, on mink. 3. Estrogen receptor and progesterone
      receptor concentrations, and potential correlation with dietary PCB consumption.
AB  - Mink (Mustela vison) were fed diets containing ocean fish (control diet, 0.0 ppm
      polychlorinated biphenyls, PCBs) or Saginaw Bay carp to provide 0.25, 0.5, or 1.0
      ppm PCBs to examine the effect of PCBs on homeostasis of binding sites for
      ovarian steroid hormones. Ranch-raised mink fed Great Lakes fish contaminated
      with PCBs, or treated with PCBs directly, have demonstrated reproductive
      impairment including anovulation, fetal resorption, delayed ovulation, increased
      gestation, and decreased litter size. Previous studies have demonstrated that
      estrogen and progesterone levels are unaltered in mink treated with PCBs,
      suggesting that the effect of PCBs on reproduction is not mediated through
      alterations in hormone homeostasis. In vitro studies have demonstrated that the
      most likely means by which PCBs exert antiestrogenic ability is through a down
      regulation of the estrogen receptor in normally estrogen-responsive tissues such
      as liver and uterus. Hepatic and uterine estrogen binding site concentrations
      were measured in female mink consuming diets containing PCBs for up to 18 mo at
      up to 1 ppm. Hepatic estrogen binding site concentrations generally decreased
      with increasing dietary PCB concentrations. Uterine estrogen binding site
      concentration did not decrease in these animals. Uterine progesterone receptor
      concentration also did not change with increasing PCB consumption. In total, the
      response of hepatic and uterine estrogen and uterine progesterone binding sites
      in mink fed diets containing Saginaw Bay carp suggests that concentrations of
      PCBs available to uterine tissue may not have been sufficient to decrease uterine
      estrogen receptor, despite their effect on hepatic estrogen receptor.

PMID- 9650574
TI  - Acute effects of a bicyclophosphate neuroconvulsant on monoamine neurotransmitter
      and metabolite levels in the rat brain.
AB  - Naive male Sprague-Dawley rats were injected intraperitoneally (i.p.) with the
      bicyclophosphate convulsant trimethylolpropane phosphate (TMPP) at dose levels
      from 0.2 to 0.6 mg/kg. Rats were observed for convulsive activity, and were
      sacrificed 15 min posttreatment. Levels of the monoamine neurotransmitters
      norepinephrine (NE), epinephrine (EPI), dopamine (DA), and serotonin (5-HT) and
      the major metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid
      (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were assayed in forebrain,
      midbrain, hindbrain, cerebellum and brainstem regions. Neurotransmitter and
      metabolite levels were compared between control rats and rats that did and did
      not experience seizures. TMPP administration induced significant decreases in
      levels of measured neurotransmitters that varied as a function of brain region,
      dose, and expression of the seizure activity. These results show that tonic or
      tonic-clonic seizures induced by TMPP administration (0.6 mg/kg) are reliably
      associated with regional decreases in serotonin, dopamine, and norepinephrine.
      Convulsive activity resulting from lower dose administrations (0.2-0.4 mg/kg) of
      TMPP result only in decreased regional levels of serotonin.

PMID- 9650575
TI  - Substrate inhibition of cruzipain is not affected by the C-terminal domain.
AB  - Endogenous and recombinant cruzipain, the major cysteine proteinase from the
      protozoan parasite Trypanosoma cruzi, exhibit differences in the protein and
      circular dichroism spectra probably attributed to the absence of the C-terminal
      domain in the recombinant enzyme. Substrate hydrolysis of both molecules at 25
      degrees C and neutral pH obeyed Michaelis-Menten kinetics whereas significant
      substrate inhibition was observed above neutral pH. The results suggest that
      substrate inhibition of cruzipain is pH-dependent, and that the C-terminal domain
      does not play an essential role in this process.

PMID- 9650576
TI  - BEN1 and ZEN1 cDNAs encoding S1-type DNases that are associated with programmed
      cell death in plants.
AB  - We describe the isolation and characterization of cDNAs encoding two DNases that
      may be involved in the programmed death of plant cells: a 35-kDa nuclease of
      barley, which had been reported to be secreted from the aleurone layer into the
      endosperm during germination and may be responsible for the digestion of nuclear
      DNA in the course of degradation (cell death) of endosperm, and a 43-kDa nuclease
      of zinnia, which appears transiently in association with differentiation to
      tracheary elements and is likely to participate in the autolysis at the final
      step of the differentiation. Genes for these nucleases of barley and zinnia were
      designated BEN1 and ZEN1, respectively. The amino acid sequence of BEN1 protein
      deduced from the nucleotide sequence of BEN1 cDNA consisted of 288 residues with
      a putative signal sequence of 23 residues. RNA gel blot analysis revealed that
      BEN1 mRNA increased in the embryo-less half seeds of barley in response to the
      application of gibberellic acid. The deduced amino acid sequence of ZEN1 protein
      consisted of 303 residues with a putative signal sequence of 25 residues.
      Temporal accumulation of ZEN1 mRNA was detected during transdifferentiation of
      zinnia mesophyll cells into tracheary elements. Significant similarities were
      found among the amino acid sequences of BEN1, ZEN1, nuclease S1 from Aspergillus
      oryzae, and two other S1-type nucleases.

PMID- 9650577
TI  - Activation of the A2A adenosine receptor inhibits nitric oxide production in
      glial cells.
AB  - Selective adenosine receptor agonists and antagonists have marked effects on the
      outcome of cerebral ischemia, and adenosine receptors are expressed on
      astrocytes. In this study we examined the effects of various adenosine receptor
      agonists on the production of nitric oxide and the induction of iNOS in
      astrocytes activated by LPS/IFN-gamma and TNF-alpha/IL-1beta and on the
      production of TNF-alpha. Treatment of the cells with the A2A receptor agonist CGS
      21680 inhibited both NO production and iNOS expression induced by stimulation
      with either LPS/IFN-gamma or TNF-alpha/IL-1beta, whereas the A1 and A3 receptor
      agonists, CPA and Cl-IB-MECA, respectively, did not have significant inhibitory
      effects. The inhibitory effect of the A2A receptor agonist was antagonized by the
      specific A2A receptor antagonist CSC. The A2A agonist also exerted a small
      inhibitory effect on the production of TNF-alpha. Similar inhibitory effects on
      the production of NO were obtained by cyclic AMP-elevating reagents, such as
      forskolin and dibutyryl cyclic AMP. Our findings suggest that activation of the
      A2A receptor inhibits NO production and iNOS expression likely via increased
      cAMP.

PMID- 9650578
TI  - Potent inhibition of specific diadenosine polyphosphate hydrolases by suramin.
AB  - The cytosolic enzymes asymmetrical diadenosine tetraphosphate hydrolase (EC
      3.6.1.17, Ap4Aase) and diadenosine triphosphate hydrolase (EC 3.6.1.29, Ap3Aase)
      are inhibited competitively by suramin. Ap4Aase and Ap3Aase were assayed in
      cytosolic rat brain extracts using fluorogenic analogues of the respective
      substrates diadenosine tetraphosphate (Ap4A) and diadenosine triphosphate (Ap3A).
      Ki values for suramin as inhibitor of Ap4Aase and Ap3Aase were 5 x 10(-6) M and 3
      x 10(-7) M, respectively. Results indicate that suramin or suramin-like
      derivatives may be useful tools to investigate diadenosine polyphosphate cleaving
      enzymes and that the intracellular diadenosine polyphosphate metabolism may be a
      pharmacological target of suramin with biological and clinical implications.

PMID- 9650579
TI  - The role of transient starch in acclimation to elevated atmospheric CO2.
AB  - Although increased concentrations of CO2 stimulate photosynthesis, this
      stimulation is often lost during prolonged exposure to elevated carbon dioxide,
      leading to an attenuation of the potential gain in yield. Under these conditions,
      a wide variety of species accumulates non-structural carbohydrates in leaves. It
      has been proposed that starch accumulation directly inhibits photosynthesis, that
      the rate of sucrose and starch synthesis limits photosynthesis, or that
      accumulation of sugars triggers changes in gene expression resulting in lower
      activities of Rubisco and inhibition of photosynthesis. To distinguish these
      explanations, transgenic plants unable to accumulate transient starch due to leaf
      mesophyll-specific antisense expression of AGP B were grown at ambient and
      elevated carbon dioxide. There was a positive correlation between the capacity
      for starch synthesis and the rate of photosynthesis at elevated CO2
      concentrations, showing that the capability to synthesize leaf starch is
      essential for photosynthesis in elevated carbon dioxide. The results show that in
      elevated carbon dioxide, photosynthesis is restricted by the rate of end product
      synthesis. Accumulation of starch is not responsible for inhibition of
      photosynthesis. Although transgenic plants contained increased levels of hexoses,
      transcripts of photosynthetic genes were not downregulated and Rubisco activity
      was not decreased arguing against a role of sugar sensing in acclimation to high
      CO2.

PMID- 9650581
TI  - 31P NMR study of the interactions between oligodeoxynucleotides containing (6-4)
      photoproduct and Fab fragments of monoclonal antibodies specific for (6-4)
      photoproduct.
AB  - A 31P nuclear magnetic resonance (NMR) study of the interactions between
      oligonucleotides containing the (6-4) photoproduct and the Fab fragments of
      monoclonal antibodies (64M3 and 64M5) recognizing the (6-4) photoproduct is
      reported. The 31P chemical shift data indicate that backbone conformation of (64)
      adduct is affected by the presence of flanking oligodeoxynucleotides, and (6-4)
      adducts with different backbone conformations are accommodated in the antigen
      binding sites of these antibodies. It was also revealed that epitopes for these
      antibodies consist of not only the (6-4) adduct but the flanking di- or tri
      deoxynucleotides on both the 5' and 3' sides as well.

PMID- 9650580
TI  - 2-Arachidonoylglycerol, an endogenous cannabinoid receptor agonist:
      identification as one of the major species of monoacylglycerols in various rat
      tissues, and evidence for its generation through CA2+-dependent and -independent
      mechanisms.
AB  - The molecular species compositions of monoacylglycerols obtained from various rat
      tissues were examined by reverse-phase high-performance liquid chromatography
      (HPLC) and gas chromatography-mass spectrometry (GC-MS) analyses. We confirmed
      that 2-arachidonoylglycerol, an endogenous cannabinoid receptor agonist, is one
      of the most abundant molecular species of monoacylglycerols in the brain.
      Substantial amounts of 2-arachidonoylglycerol were also found in the liver,
      spleen, lung and kidney, but the levels were considerably lower than that in the
      brain. We found that a small amount of 2-arachidonoylglycerol was generated in a
      brain homogenate during incubation in the absence of Ca2+. Importantly, the
      generation of 2-arachidonoylglycerol was markedly augmented in the presence of
      Ca2+, suggesting that Ca2+ plays a key role in regulation of the generation of 2
      arachidonoylglycerol in this tissue.

PMID- 9650582
TI  - Different degradation pathways for heterologous glycoproteins in yeast.
AB  - Rat nerve growth factor receptor ectodomain (NGFRe) and Escherichia coli beta
      lactamase were translocated into the yeast endoplasmic reticulum (ER),
      glycosylated, misfolded and rapidly degraded. NGFRe underwent ATP-dependent
      thermosensitive degradation independently of vesicular transport. Since no
      evidence for degradation by the cytoplasmic 26S proteosome complex could be
      obtained, NGFRe appeared to be degraded in the ER. Beta-lactamase exited the ER
      by vesicular traffic and was transported from the Golgi via the Vps10 receptor
      pathway to the vacuole for degradation. Machineries in the ER and the Golgi
      appear to recognize distinct structural features on misfolded heterologous
      proteins and guide them to different degradation pathways.

PMID- 9650583
TI  - Localization of fractalkine and CX3CR1 mRNAs in rat brain: does fractalkine play
      a role in signaling from neuron to microglia?
AB  - Localization of the mRNAs for fractalkine, a CX3C chemokine, and for its receptor
      CX3CR1 was investigated in the rat brain. In situ hybridization study revealed
      that fractalkine mRNA was dominantly expressed in neuronal cells particularly in
      the olfactory bulb, cerebral cortex, hippocampus, caudate putamen and nucleus
      accumbens. In vitro study using enriched neuronal or glial culture supported the
      dominant expression of fractalkine mRNA in neurons. On the other hand, CX3CR1
      mRNA was dominantly expressed in glial cells throughout the whole brain. The in
      vitro study suggested the cells expressing CX3CR1 mRNA are microglia, not
      astrocytes or neurons. Fractalkine appears to function as a signal molecule from
      neuron to microglia.

PMID- 9650584
TI  - Topological and functional analysis of the rat liver carnitine
      palmitoyltransferase 1 expressed in Saccharomyces cerevisiae.
AB  - The rat liver carnitine palmitoyltransferase 1 (L-CPT 1) expressed in
      Saccharomyces cerevisiae was correctly inserted into the outer mitochondrial
      membrane and shared the same folded conformation as the native enzyme found in
      rat liver mitochondria. Comparison of the biochemical properties of the yeast
      expressed L-CPT 1 with those of the native protein revealed the same detergent
      lability and similar sensitivity to malonyl-CoA inhibition and affinity for
      carnitine. Normal Michaelis-Menten kinetics towards palmitoyl-CoA were observed
      when careful experimental conditions were used for the CPT assay. Thus, the
      expression in S. cerevisiae is a valid model to study the structure-function
      relationships of L-CPT 1.

PMID- 9650585
TI  - Identification of multispecific organic anion transporter 2 expressed
      predominantly in the liver.
AB  - In the present study, we demonstrate that NLT (novel liver-specific transport
      protein) is a multispecific organic anion transporter of the liver. The amino
      acid sequence of NLT shows 42% identity to that of the renal multispecific
      organic anion transporter, OAT1. When expressed in Xenopus laevis oocytes, NLT
      mediated uptake of organic anions, such as salicylate, acetylsalicylate, PGE2,
      dicarboxylates and p-aminohippurate. [14C]Salicylate uptake via NLT was saturable
      (Km = 88.8 +/- 23.4 microM) and sodium-independent. Expression of the mRNA of NLT
      was detected in the liver and kidney (liver >> kidney). We propose that NLT be
      renamed OAT2.

PMID- 9650586
TI  - The carboxy-terminal region of adenovirus E1A activates transcription through
      targeting of a C-terminal binding protein-histone deacetylase complex.
AB  - Binding of the C-terminal binding protein, CtBP, to the adenovirus E1A moiety of
      a Gal4-E1A fusion protein abolishes conserved region (CR) 1-dependent
      transcription activation. In contrast, a non-promoter targeted E1A peptide,
      capable of binding CtBP, can induce transcription from the proliferating cell
      nuclear antigen (PCNA) promoter. CtBP is shown here to bind the histone
      deacetylase HDAC1, suggesting that a promoter targeted CtBP-HDAC1 complex can
      silence transcription from the PCNA promoter through a deacetylation mechanism.
      Expression of the CtBP binding domain of E1A is sufficient to alleviate
      repression, possibly due to the displacement of the CtBP-HDAC1 complex from the
      promoter.

PMID- 9650587
TI  - A G.U base pair in the eukaryotic selenocysteine tRNA is important for
      interaction with SePF, the putative selenocysteine-specific elongation factor.
AB  - In Escherichia coli, selenocysteine biosynthesis and incorporation into
      selenoproteins requires the action of four gene products, including the
      specialized selenocysteine tRNA(Sec) and elongation factor SELB, different from
      the universal EF-Tu. In this regard, the situation is less clear in eukaryotes,
      but we previously reported the existence of SePF, a putative SELB homologue. The
      secondary structure of the tRNA(Sec) differs slightly in eukaryotes, due to a
      change in the lengths of several stems. Two non-Watson-Crick base pairs, G5a x
      U67b and U6 x U67, reside in the acceptor stem and are conserved in the course of
      evolution. Since it has already been reported that changing them to Watson-Crick
      base pairs did not affect the serylation or selenylation levels of tRNA(Sec), we
      asked whether these non-Watson-Crick base pairs are required for the interaction
      with SePF. To this end, tRNA(Sec) variants carrying Watson-Crick changes at these
      positions were tested for their ability to maintain the interaction with SePF. In
      these assays, the tRNA(Sec)-SePF interaction was determined by the protective
      action it confers against hydrolysis of the amino acid ester bond, under basic
      conditions. All the changes introduced at U6 x U67 did not significantly affect
      the interaction. Interestingly, however, the G5a x U67b to G5a-C67b substitution
      was sufficient, by itself, to lead to unprotection of the ester bond. Therefore,
      our finding strongly suggests that SePF is unable to interact with a tRNA(Sec)
      mutant version carrying a Watson-Crick G5a-C67b instead of the wild-type G5a x
      U67b base pair, establishing that G5a x U67b constitutes a structural determinant
      for SePF interaction.

PMID- 9650588
TI  - Purification and properties of exopolyphosphatase isolated from Saccharomyces
      cerevisiae vacuoles.
AB  - An exopolyphosphatase (polyPase) with a specific activity of 60 U/mg protein has
      been purified from the vacuolar sap of Saccharomyces cerevisiae. The molecular
      mass of the intact enzyme was found to be 245 kDa. It is highly specific towards
      high-molecular polyphosphates (polyP). The activity with polyP9 is 24% of that
      with polyP208. The apparent Km for polyP15 and polyP208 hydrolysis is 93 and 2.4
      microM, respectively. The enzyme is slightly active with polyP3 and adenosine-5'
      tetraphosphate, but does not hydrolyze pyrophosphate, ATP, GTP and p
      nitrophenylphosphate. It is stimulated by divalent metal cations. Co2+, the best
      activator, stimulates it 6-fold. Antibodies that inhibit the cell envelope and
      cytosol polyPases of S. cerevisiae have no effect on the vacuolar polyPase. The
      vacuolar polyPase differs from other yeast polyPases in molecular mass, substrate
      specificity and effects of activators.

PMID- 9650589
TI  - Coupling of proton source and sink via H+-migration along the membrane surface as
      revealed by double patch-clamp experiments.
AB  - Long-range proton transfer along the surface of black lipid bilayers was observed
      between two integral membrane channels (gramicidins), one operating as a proton
      source, the other as a sink, by patch-clamp technique. In contrast, potassium
      ions were shown to equilibrate with the aqueous bulk phase before being consumed.
      Both channels opened and closed simultaneously only if the charge between them
      was carried by protons. In this case an anomalous high conductance between two
      patched membrane fragments was measured, each of them containing one single
      gramicidin channel. The coupled state disappeared when the distance between these
      two channels was increased above the critical value. The latter was shown to
      increase with the channel lifetime. Our results support the idea of the
      'localized' proton coupling, in which protons that have been pumped across
      membranes migrate along the membrane surface to reach another membrane protein
      that utilizes the established pH gradient.

PMID- 9650590
TI  - Identification of an uncoupling mutation affecting the b subunit of F1F0 ATP
      synthase in Escherichia coli.
AB  - A specific b subunit arginine, b(Arg-36) in Escherichia coli, displays
      evolutionary conservation among bacterial F1F0 ATP synthases. Site-directed
      mutagenesis was used to generate a collection of mutations affecting b(Arg-36).
      The phenotype differed depending upon the substitution, and the b(Arg-36-Glu) and
      b(Arg-36-Ile) substitutions virtually abolished enzyme function. Although the
      total amounts of F1F0 ATP synthase present in the membranes prepared from mutant
      strains were reduced, the primary effect of the b(Arg-36) substitutions was on
      the activities of the intact enzyme complexes. The most interesting result was
      that the b(Arg-36-Glu) substitution results in the uncoupling of a functional F0
      from F1 ATP hydrolysis activity.

PMID- 9650591
TI  - T-cadherin and signal-transducing molecules co-localize in caveolin-rich membrane
      domains of vascular smooth muscle cells.
AB  - Cadherins are a family of cellular adhesion proteins mediating homotypic cell
      cell binding. In contrast to classical cadherins, T-cadherin does not possess the
      transmembrane and cytosolic domains known to be essential for tight mechanical
      coupling of cells, and is instead attached to the cell membrane by a
      glycosylphosphatidylinositol (GPI) anchor. This study explores the hypothesis
      that T-cadherin might function as a signal-transducing protein. Membranes from
      human and rat vascular smooth muscle cells were fractionated using Triton X-100
      solubilization and density gradient centrifugation techniques. We demonstrate
      that T-cadherin is enriched in a minor detergent-insoluble low-density membrane
      domain and co-distributes with caveolin, a marker of caveolae. This domain was
      enriched in other GPI-anchored proteins (CD-59, uPA receptor) and signal
      transducing molecules (G alpha s protein and Src-family kinases), but completely
      excluded cell-cell and cell-matrix adhesion molecules (N-cadherin and beta1
      integrin). Coupling of T-cadherin with signalling molecules within caveolae might
      enable cellular signal transduction.

PMID- 9650592
TI  - Crystal structure of domain E of Thermus flavus 5S rRNA: a helical RNA structure
      including a hairpin loop.
AB  - The synthetic RNA fragment 5'-CUGGGCGG(GCGA)CCGCCUGG (nucleotides in parentheses
      indicate the loop region) corresponds to the natural sequence of domain E from
      nucleotides 79-97 of the Thermus flavus 5S rRNA including a hairpin loop. The RNA
      structure determined at 3.0 A and refined to an R-value of 24.1% also represents
      the first X-ray structure GNRA tetraloop. The loop is in distinctly different
      conformation from other GNRA tetraloops analyzed by NMR. The conformation of the
      two molecules in the asymmetric unit is influenced and stabilized by specific
      intermolecular contacts. The structural features presented here give evidence for
      the ability of RNA molecules to adapt to specific environments.

PMID- 9650593
TI  - Role of copper during carbon monoxide binding to terminal oxidases.
AB  - Under fully reduced conditions, reassociation kinetics of CO were studied in
      several terminal oxidases containing copper in their binuclear center. The
      purified Paracoccus denitrificans ba3-type quinol oxidase was found to recombine
      with CO monophasically (tau 25-30 ms) like oxidases of the bo type from
      Escherichia coli, the caa3 type from Bacillus halodurans FTU, and the bo type
      from Methylobacillus flagellatum KT. Oxidase of the aa3 type from bovine heart
      recombined with CO monophasically at a higher rate (tau 16-19 ms) than the
      studied copper-containing bacterial oxidases. After prolonged incubation in the
      presence of CO, oxidases of the ba3 and aa3 types changed their CO-binding
      properties. The contribution of the slow component was diminished while new fast
      components arose. Measurement of the metal content in the oxidases indicated that
      during the incubation, the enzymes lost their copper, the process being
      accompanied by the appearance of a fast CO recombination rate resembling that of
      the non-copper oxidases of the bd type from E. coli and the bb type from Bacillus
      halodurans FTU. This points to a role of copper in CO binding by terminal
      oxidases.

PMID- 9650594
TI  - Publication of negative results is an essential part of the scientific process.

PMID- 9650595
TI  - Proteolysis of poly(ADP-ribose) polymerase by caspase 3: kinetics of cleavage of
      mono(ADP-ribosyl)ated and DNA-bound substrates.
AB  - Poly(ADP-ribose) polymerase (PARP) is an abundant nuclear enzyme which is
      responsible for synthesis of poly(ADP-ribose) in response to DNA damage caused by
      numerous agents and during DNA base excision repair. After DNA damage, the enzyme
      binds to nicks in DNA through its N-terminal zinc fingers and catalyzes the
      formation of poly(ADP-ribose) on various nuclear acceptors including itself. When
      DNA damage is extensive, cells induce their own demise by activating the
      proteases that induce apoptosis (caspases) which cleave PARP and other death
      substrates. Here we report the development of a new approach to investigate the
      sensitivity of mono(ADP-ribosyl)ated and DNA-bound PARP to cleavage during
      apoptosis. The development of a stoichiometric labeling procedure of the enzyme
      has allowed us to evaluate the catalytic properties of caspase 3 toward mono(ADP
      ribosyl)ated PARP at various enzyme:substrate molar ratios. We show that low
      levels of automodification (< or = 3 U of ADP-ribose per chain) do not inhibit
      the proteolysis of the substrate. In addition, we demonstrate that binding of
      unmodified PARP to DNA influences the kinetics of its cleavage by caspase 3.

PMID- 9650596
TI  - Radiosensitivity in ataxia telangiectasia fibroblasts is not associated with
      deregulated apoptosis.
AB  - Ataxia telangiectasia (AT) is an autosomal recessive human disorder featuring
      diverse clinical abnormalities including proneness to cancer and extreme
      sensitivity to ionizing radiation. Although cells from AT patients exhibit faulty
      activation of the p53 signal transduction pathway at early times after radiation
      exposure, it has been proposed that high levels of DNA damage persisting in AT
      cells may up-regulate p53 through an ATM-independent mechanism at late times
      after irradiation, leading to cell death by apoptosis. In this study we
      demonstrate that diploid skin fibroblast strains homozygous for the AT mutation
      fail to up-regulate p53 protein at late times (< or = 48 h) after irradiation
      with 60Co gamma rays. Moreover, exposure of normal and AT fibroblasts to a dose
      of 8 Gy does not result in a significant increase in the fraction of apoptotic
      cells. Since this treatment reduces the clonogenic potential of human cells by at
      least two orders of magnitude, we conclude that apoptosis is not the primary
      mechanism of cell death induced by ionizing radiation in human normal and AT
      fibroblast cultures. Therefore, our results are not in accordance with the
      current hypothesis suggesting that increased radiosensitivity of AT cells is
      associated with deregulated apoptosis.

PMID- 9650597
TI  - Comparison between pulsed-field gel electrophoresis and the comet assay as
      predictive assays for radiosensitivity in fibroblasts.
AB  - The radiosensitivity of skin fibroblasts derived from patients as measured in
      vitro by a clonogenic survival assay appears to correlate with the risk of
      developing severe late reactions to radiation. Unfortunately, these assays are
      clinically impractical as a predictive test for radiosensitivity. The purpose of
      this study was to assess the utility of two possible surrogate assays for
      radiosensitivity, pulsed-field gel electrophoresis (PFGE) and single-cell gel
      electrophoresis (comet assay), both of which can be used to measure DNA double
      strand breaks. Twenty-three nontransformed human fibroblast cell lines exhibiting
      a range of radiosensitivities were studied with both of these assays. The results
      were correlated with measurements of radiosensitivity obtained as part of a
      larger study examining the correlation between cellular radiosensitivity and
      clinical response. [2-(14)C]Thymidine-labeled confluent cultures were irradiated
      at 1.0 Gy/min with doses of 0 to 150 Gy. After allowing 4 h for repair at 37
      degrees C, cells were trypsinized and aliquots were used for preparing slides for
      the comet assay. After neutral lysis and electrophoresis, the slides were stained
      with ethidium bromide and 50 comet moments were measured for each dose. The
      remainder of the cells were formed into agarose plugs and, after neutral lysis,
      were subjected to PFGE. The fraction of activity released (FAR) from the well was
      measured by scintillation counting of appropriate segments of each gel lane.
      Cellular radiosensitivity was measured with a standard clonogenic assay at a low
      dose rate of 1.2 cGy/min, and the dose that resulted in a surviving fraction of
      0.01 (D0.01) was calculated. The slope of the plot of comet moment as a function
      of dose for each cell line did not correlate with D0.01 (R = 0.36, P > 0.1). In
      contrast, the slope of the FAR as a function of dose had a weak inverse
      correlation with D0.01 (R = 0.43 and P = 0.05) such that the more radiosensitive
      cell lines exhibited a steeper dose response for FAR. Although the correlation
      between the slope of the dose response for FAR and D0.01 was weak, refinement of
      the PFGE technique may provide a potentially useful predictive assay for
      radiosensitivity.

PMID- 9650598
TI  - MYC mRNA abundance is unchanged in subcultures of HL60 cells exposed to power
      line frequency magnetic fields.
AB  - Epidemiological data have not demonstrated conclusively that there exists an
      association between exposure to power-line frequency electric and magnetic fields
      (EMFs) and cancer. Some laboratory studies performed to investigate possible
      mechanisms for such an association reported biological effects of EMF exposure,
      but attempts to confirm some such reports have had mixed success. The most
      publicized experiments in this regard were studies on the purported EMF-induced
      increase in MYC expression in HL60 cells. To address the accuracy and
      reproducibility of this effect, HL60 cells were exposed to 6-microT 60 Hz
      magnetic fields, and MYC expression was measured. Assay methods and exposure
      conditions were as close as practical to those of the investigators that
      originally reported a positive effect. A chemical agent was used to demonstrate
      that the cells were responsive to a known stimulus and that the experimental
      system was sufficiently sensitive to detect such a stimulus. The experimental
      system had sufficiently low basal variability to allow the detection of effects
      of the magnitude that had been reported previously. Using either cells from a
      commercial source or cells supplied by the original investigators, no evidence
      was obtained to support the hypothesis that EMF exposure could induce MYC
      expression.

PMID- 9650599
TI  - Transfection of a vector expressing wild-type p53 into cells of two human glioma
      cell lines enhances radiation toxicity.
AB  - Replication-deficient adenovirus (Adv5)-based vectors containing either wild-type
      p53 or the beta-gal marker gene were introduced into cells of the T98G (p53
      mutant) and U87MG (p53 wild-type) human glioma cell lines. The wild-type p53 gene
      was successfully expressed in each cell line as shown by flow cytometry and
      Western blotting. The presence of the p53-expressing vector was toxic in both
      cell lines compared to control cells or to those containing the beta-gal vector.
      At levels of Adv5p53 vector that produced detectable toxicity, the effect of
      irradiation was enhanced, producing a twofold increase in cell killing. In the
      T98G cells, the presence of the p53 vector resulted in an increase in the number
      of cells undergoing apoptosis after irradiation, whereas a smaller and only
      additive response was observed in the U87MG cells. Conversely, an increase in
      micronucleus formation, indicating corrupt mitotic activity, was observed in
      irradiated Adv5p53-positive U87MG cells but not in T98G cells. These data suggest
      that p53-expressing vectors effectively enhance radiation lethality in these
      human glioma cell lines, but that the mechanism of action cannot be simply
      related to activation of the p53-dependent pathway to apoptosis.

PMID- 9650600
TI  - Evaluation of lactate as a 1H nuclear magnetic resonance spectroscopy index for
      noninvasive prediction and early detection of tumor response to radiation therapy
      in EMT6 tumors.
AB  - In a recent study (Int. J. Radiat. Oncol. Biol. Phys. 36, 635-639, 1996), 1H
      nuclear magnetic resonance (NMR) spectroscopy was used to demonstrate significant
      decreases in lactate levels after gamma irradiation of radiosensitive RIF-1
      tumors in vitro. For comparison, we have examined the effects of gamma radiation
      on lactate levels in the more radioresistant EMT6 tumor. Single-slice (5-6 mm
      thick) localized 1H spectra of subcutaneous RIF-1 (untreated) and EMT6 tumors
      (pretreatment, 24 and 48 h postirradiation with 4, 10 or 20 Gy of gamma
      radiation) were measured by the selective multiple quantum coherence transfer
      method (Sel-MQC, approximately 4 min acquisition time). Both pretreatment lactate
      levels and pretreatment lactate dehydrogenase (LDH) activities were found to be
      similar in RIF-1 and EMT6 tumors, suggesting that steady-state lactate levels are
      unlikely to be reliable indices for predicting response to radiation therapy.
      After 10 Gy gamma irradiation, EMT6 tumors showed a 21% decrease relative to
      pretreatment lactate levels at 48 h (1.04 +/- 0.22 to 0.82 +/- 0.16; P = 0.06);
      after 20 Gy a 40% decrease was observed at 48 h (1.34 +/- 0.27 to 0.81 +/- 0.10;
      P = 0.07). No significant changes in lactate levels were observed in control EMT6
      tumors or in tumors treated with 4 Gy of gamma radiation, in contrast to changes
      detected previously in RIF-1 tumors, which showed a significant decrease in
      lactate by 48 h for both 2 and 4 Gy. The decreased effect of radiation on lactate
      levels in EMT6 compared to RIF-1 tumors may be attributed to the higher hypoxic
      fraction and lower radiosensitivity of EMT6 tumors (Int. J. Radiat. Oncol. Biol.
      Phys. 10, 695-712, 1984). The decrease in lactate levels did not, however,
      strictly reflect the extent of the response to therapy for the high dose of 20
      Gy. This study together with our earlier study (Int. J. Radiat. Oncol. Biol.
      Phys. 36, 635-639, 1996) provides evidence to support the hypothesis that changes
      in steady-state tumor lactate levels may serve as sensitive early indices of
      tumor response to gamma radiation at doses of the order of 2 to 4 Gy.

PMID- 9650601
TI  - Effects of ionizing radiation (neutrons/gamma rays) on plasma lipids and
      lipoproteins in rats.
AB  - Male Wistar rats weighing 250 g were exposed to 4 Gy of neutrons/gamma radiation
      (3.33 Gy of neutrons and 0.66 Gy of gamma rays). After whole-body irradiation,
      plasma cholesterol and phospholipid levels increased up to 62 and 37%,
      respectively, at day 4 and then returned to control values 12 days after
      irradiation. Plasma triglyceride concentrations decreased concomitantly with
      decreased food intake after irradiation but remained higher than in pair-fed
      control rats. Plasma lipoproteins were separated by ultracentrifugation on a
      density gradient (1.006-1.210 g/ml). Four days after irradiation, most of the
      cholesterol (62% compared to 31% in controls, P < 0.001) is transported by
      apolipoprotein E-rich high-density lipoproteins. At the same time, plasma levels
      of apolipoproteins B and E were increased by 28 and 65%, respectively, while
      those of apolipoproteins AI and AIV were reduced by 21 and 59%, respectively.
      While in the liver of irradiated rats the apolipoprotein B/E receptor number was
      not modified, the hydroxymethylglutaryl coenzyme A reductase activity was
      fivefold higher than in control pair-fed rats. Four days after irradiation, the
      susceptibility of lipoproteins to peroxidation, as measured by the formation of
      conjugated dienes in the presence of Cu2+, was markedly increased while plasma
      vitamin E levels were decreased, demonstrating that irradiation reduces
      antioxidant stores markedly. These results suggest that such modified
      lipoproteins could be involved in radiation-induced vascular damage.

PMID- 9650602
TI  - Effects of gamma radiation on levels of brain metallothionein and lipid
      peroxidation in transgenic mice.
AB  - The induction of metallothionein (MT) synthesis in the brain was investigated in
      MT-I isoform-overexpressing transgenic (MT-I*) and control mice after exposure to
      increasing doses of 2 to 20 Gy of whole-body gamma radiation. Although the MT-I
      isoform was the major isoform of MT in this transgenic mouse, the other isoforms,
      MT-II and MT-III, were also present in the brain. The total concentration of MT
      in the brain was measured by a cadmium-binding assay, while zinc and lipid
      peroxides were measured by atomic absorption spectrophotometry and by the
      thiobarbituric acid method, respectively. In MT-I* mice at 24 h after radiation
      exposure, the level of MT in the brain was increased from a basal level of 44.4
      +/- 4.0 microg/g to a maximum level of 91.0 +/- 9.0 microg/g after 5 Gy and
      remained high after 10 and 20 Gy. In a time-course experiment with 5 Gy, the
      concentration of MT in the brain of MT-I* mice increased at 3 h and reached a
      maximum of 175.3 +/- 15.3 microg/g at 6 h. This high level of MT remained
      unchanged for 48 h after radiation exposure. Metallothionein was not induced
      markedly in the brains of control mice either at 24 h after exposure to 2-20 Gy
      gamma radiation or at different times after exposure to 5 Gy gamma radiation. In
      both strains of mice, the total concentration of zinc in the brain decreased with
      increasing radiation dose. No differences in lipid peroxide levels were seen in
      control mice exposed to 5 Gy at 6 and 12 h or after exposure to three other doses
      (2, 10 and 20 Gy) at 24 h. Slight increases (1.35 and 1.22, respectively) in
      lipid peroxide levels were observed in control mice at 24 and 48 h after exposure
      to 5 Gy. Lipid peroxide levels in the brain were not changed in irradiated MT-I*
      mice. The results show a marked increase in the levels of MT in the brain of
      transgenic mice after exposure to gamma radiation. The induced synthesis of MT
      may be only one of several mechanisms that prevent the induction of lipid
      peroxidation in the brain by gamma radiation.

PMID- 9650603
TI  - Radon-progeny exposure and lung cancer risk in a cohort of Newfoundland fluorspar
      miners.
AB  - Although radon is a well-established lung carcinogen, there are uncertainties
      concerning the exposure-response relationship, whether exposures in early life
      are particularly hazardous, and how smoking affects the risks associated with
      radon exposure. A cohort study of the mortality experience of 1,743 underground
      fluorspar miners and 321 surface workers from 1950 to 1984 reported previously
      has been extended to include 6 additional years of follow-up (1985-1990). A
      statistically significant relationship was noted between radon-progeny exposure
      and risk of lung cancer mortality. Our analysis found no effect for age at first
      exposure. Attained age was strongly predictive of excess relative risk (ERR) per
      working level month (WLM) of radon exposure, falling from 0.025 for those aged
      less than 50 years to 0.002 for those 70 years or older. An inverse exposure-rate
      effect was also observed, wherein for equal total exposure, a high exposure rate
      (and short duration) is less harmful than a low exposure rate (and long
      duration). The ERR/WLM increased from 0.0019 for exposures of less than 10 years
      to 0.0076 for exposures of 20 or more years. The analysis of time-since-exposure
      windows revealed a greater ERR/WLM for exposures received in more recent periods,
      similar to the result for time since last exposure. Excess relative risks per WLM
      were higher for current smokers than for nonsmokers (never and former smokers).
      Analyses were consistent with a multiplicative relationship between radon-progeny
      exposure and current smoking and the risk of lung cancer. The assessment of radon
      exposure and lung cancer risk should incorporate the effects of exposure rate,
      time since exposure, smoking status and attained age.

PMID- 9650604
TI  - Statistical modeling of carcinogenic risks in dogs that inhaled 238PuO2.
AB  - Combined analyses of data on 260 life-span beagle dogs that inhaled 238PuO2 at
      the Inhalation Toxicology Research Institute (ITRI) and at Pacific Northwest
      National Laboratory (PNNL) were conducted. The hazard functions (age-specific
      risks) for incidence of lung, bone and liver tumors were modeled as a function of
      cumulative radiation dose, and estimates of lifetime risks based on the combined
      data were developed. For lung tumors, linear-quadratic functions provided an
      adequate fit to the data from both laboratories, and linear functions provided an
      adequate fit when analyses were restricted to doses less than 20 Gy. The
      estimated risk coefficients for these functions were significantly larger when
      based on ITRI data compared to PNNL data, and dosimetry biases are a possible
      explanation for this difference. There was also evidence that the bone tumor
      response functions differed for the two laboratories, although these differences
      occurred primarily at high doses. These functions were clearly nonlinear (even
      when restricted to average skeletal doses less than 1 Gy), and evidence of
      radiation-induced bone tumors was found for doses less than 0.5 Gy in both
      laboratories. Liver tumor risks were similar for the two laboratories, and linear
      functions provided an adequate fit to these data. Lifetime risk estimates for
      lung and bone tumors derived from these data had wide confidence intervals, but
      were consistent with estimates currently used in radiation protection. The dog
      based lifetime liver tumor risk estimate was an order of magnitude larger than
      that used in radiation protection, but the latter also carries large
      uncertainties. The application of common statistical methodology to data from two
      studies has allowed the identification of differences in these studies and has
      provided a basis for common risk estimates based on both data sets.

PMID- 9650605
TI  - The linear-quadratic model and most other common radiobiological models result in
      similar predictions of time-dose relationships.
AB  - One of the fundamental tools in radiation biology is a formalism describing time
      dose relationships. For example, there is a need for reliable predictions of
      radiotherapeutic isoeffect doses when the temporal exposure pattern is changed.
      The most commonly used tool is now the linear-quadratic (LQ) formalism, which
      describes fractionation and dose-protraction effects through a particular
      functional form, the generalized Lea-Catcheside time factor, G. We investigate
      the relationship of the LQ formalism to those describing other commonly discussed
      radiobiological models in terms of their predicted time-dose relationships. We
      show that a broad range of radiobiological models are described by formalisms in
      which a perturbation calculation produces the standard LQ relationship for dose
      fractionation/protraction, including the same generalized time factor, G. This
      approximate equivalence holds not only for the formalisms describing binary
      misrepair models, which are conceptually similar to LQ, but also for formalisms
      describing models embodying a very different explanation for time-dose effects,
      namely saturation of repair capacity. In terms of applications to radiotherapy,
      we show that a typical saturable repair formalism predicts practically the same
      dependences for protraction effects as does the LQ formalism, at clinically
      relevant doses per fraction. For low-dose-rate exposure, the same equivalence
      between predictions holds for early-responding end points such as tumor control,
      but less so for late-responding end points. Overall, use of the LQ formalism to
      predict dose-time relationships is a notably robust procedure, depending less
      than previously thought on knowledge of detailed biophysical mechanisms, since
      various conceptually different biophysical models lead, in a reasonable
      approximation, to the LQ relationship including the standard form of the
      generalized time factor, G.

PMID- 9650606
TI  - Physical and biological interface dose effects in tissue due to X-ray-induced
      release of secondary radiation from metallic gold surfaces.
AB  - Dose enhancement up to more than a factor of 100 was found in an environment of
      tissue-equivalent polymethylmethacrylate (PMMA) close to the surface of a thin
      metallic gold foil. The enhancement factors were determined for heavily filtered
      X rays (40 to 120 kV tube potential) under backscatter conditions, using thin
      film radiation detectors with sub-micrometer resolution. The secondary electrons
      were found to range up to some 10 microm in tissue-equivalent material.
      Correspondingly, enhanced biological effects could be shown in vitro, using
      monolayers of C3H 10T1/2 mouse embryo fibroblasts exposed in intimate contact
      with the gold surface. The decay of the survival curves of cells irradiated on
      gold was significantly steeper than for those obtained from irradiation between
      PMMA disks with the same dose, also giving biological evidence for significantly
      enhanced doses at the gold interface. The shape of the inactivation curves
      resembled those for high-LET radiation, lacking a pronounced shoulder at the
      lower doses. Quantitatively, doses of e.g. 50 mGy (80 kV X rays) in homogeneous
      PMMA caused about 35% cell killing and 200 mGy about 80% when the cells were
      irradiated at the gold surface. From a comparison of these inactivation numbers
      with those found for irradiation between PMMA disks, biological dose enhancement
      factors for the cell system considered ranged up to about a factor of 50. In
      addition to cell inactivation, the in vitro irradiations of C3H 10T1/2 cells
      adjacent to the gold surface resulted in increased rates of oncogenic
      transformation. A dose of 100 mGy 80 kV X rays (measured in homogeneous PMMA)
      caused a frequency at an inserted gold surface comparable to that obtained with a
      dose of about 4.5 Gy of 60Co gamma rays in homogeneous PMMA.

PMID- 9650607
TI  - Migration of electrons and holes in crystalline d(CGATCG)-anthracycline complexes
      X-irradiated at 4 K.
AB  - Electrons and holes generated in irradiated DNA migrate to stable trapping sites.
      Protonation and deprotonation reactions at these sites promote the trapping of
      electrons and holes, thereby inhibiting further migration. The extent of
      migration determines the final distribution of damage in irradiated DNA. In this
      study, electron and hole migration is investigated in a crystalline DNA hexamer
      intercalated with an anthracycline drug. The intercalator is no further than 2
      base pairs away from any DNA base. From EPR measurements, there is no evidence of
      DNA-centered radicals in the irradiated DNA hexamer. The aromatic region of the
      anthracycline intercalator evidently sequesters most or all of the electrons and
      most of the holes. Further hole trapping and radical stabilization appear to
      occur on the anthracycline's amino sugar group, which is nestled in the minor
      groove of the hexamer. The relatively large yield of this proposed amino sugar
      radical suggests that holes generated in the DNA solvation shell migrate to the
      amino sugar, where they become trapped. This would be the first observation of a
      radical formed by the direct effect of low-dose, low-LET radiation that is
      trapped within the DNA helix, yet lies outside of the stacked bases. With respect
      to holes generated in the DNA bases at 4 K, we conclude that most, if not all,
      are capable of migrating to an intercalator < or = 2 base pairs away. With
      respect to dry electrons, we conclude that anthracycline competes effectively for
      electron trapping over a region of at least 2 base pairs; our experiments cannot
      distinguish between electron attachment to the bases followed by transfer to the
      intercalator and direct attachment to the intercalator.

PMID- 9650608
TI  - The effects of delta rays on the number of particle-track traversals per cell in
      laboratory and space exposures.
AB  - It is a common practice to estimate the number of particle-track traversals per
      cell or cell nucleus as the product of the ion's linear energy transfer (LET) and
      cell area. This practice ignores the effects of track width due to the lateral
      extension of delta rays. We make estimates of the number of particle-track
      traversals per cell, which includes the effects of delta rays using radial
      cutoffs in the ionization density about an ion's track of 1 mGy and 1 cGy.
      Calculations for laboratory and space radiation exposures are discussed, and show
      that the LET approximation provides a large underestimate of the actual number of
      particle-track traversals per cell from high-charge and energy (HZE) ions. In
      light of the current interest in the mechanisms of radiation action, including
      signal transduction and cytoplasmic damage, these results should be of interest
      for radiobiology studies with HZE ions.

PMID- 9650609
TI  - Adaptive response in embryogenesis: I. Dose and timing of radiation for reduction
      of prenatal death and congenital malformation during the late period of
      organogenesis.
AB  - An adaptive response was demonstrated during embryogenesis in mice. Whole-body
      irradiation at a dose of 0-50 cGy was given to condition pregnant ICR mice on day
      9 to day 11 of gestation. Then their whole bodies were exposed to a challenging
      dose of 5 Gy on the next day. The numbers of living fetuses, prenatal deaths and
      living fetuses with external gross malformations were determined on day 19. A
      conditioning dose of 30 cGy on day 11 significantly increased the rate of living
      fetuses and reduced the incidence of congenital malformations induced by a 5-Gy
      dose on day 12. This indicates the existence of a critical dose and timing for
      administering a conditioning dose for radioadaptation during the late period of
      organogenesis in mice. The possible mechanisms involved are discussed.

PMID- 9650610
TI  - Cancer cells under the fire of combined therapies.

PMID- 9650611
TI  - New prodrug activation gene therapy for cancer using cytochrome P450 4B1 and 2
      aminoanthracene/4-ipomeanol.
AB  - Vector-mediated transfer of prodrug-activating genes provides a promising means
      of cancer gene therapy. In a search for more selective and more potent
      bioactivating enzymes for gene therapy of malignant brain tumors, the toxicity
      generating capacity of the rabbit cytochrome P450 isozyme CYP4B1 was
      investigated. Rabbit CYP4B1, but not rat or human isozymes, efficiently converts
      the inert prodrugs, 2-aminoanthracene (2-AA) and 4-ipomeanol (4-IM), into highly
      toxic alkylating metabolites. Toxicity of these two prodrugs was evaluated in
      culture in parental and genetically modified rodent (9L) and human (U87) glioma
      cell lines stably expressing CYP4B1, and in vivo in a subcutaneous 9L tumor model
      in nude mice. The most sensitive CYP4B1-expressing glioma clone, 9L4B1-60,
      displayed an LD50 of 2.5 microM for 2-AA and 4-IM after 48 h of prodrug
      incubation, whereas 20 times higher prodrug concentrations did not cause any
      significant toxicity to control cells. Substantial killing of control tumor cells
      by 2-AA was achieved by co-culturing these cells with CYP4B1-expressing cells at
      a ratio of 100:1, and toxic metabolites could be transferred through medium. In
      both CYP4B1-expressing cells and co-cultured control cells, prodrug bioactivation
      was associated with DNA fragmentation, as assayed by fluorescent TUNEL assays and
      by annexin V staining. Alkaline elution of cellular DNA after exposure to 4-IM
      revealed extensive protein-DNA crosslinking with single-strand breakage. Growth
      of 9L-4B1 tumors in nude mice was inhibited by intraperitoneal injection of 4-IM
      with minimal side effects. Potential advantages of the CYP4B1 gene therapy
      paradigm include: the low concentrations of prodrug needed to kill sensitized
      tumor cells; low prodrug conversion by human isozymes, thus reducing toxicity to
      normal cells; a tumor-killing bystander effect that can occur even without cell
      to-cell contact; and the utilization of lipophilic prodrugs that can penetrate
      the blood-brain barrier.

PMID- 9650612
TI  - Suppression of immunological response against a transgene product delivered from
      microencapsulated cells.
AB  - A potential obstacle to successful gene therapy for some patients is the in vivo
      production of neutralizing antibodies against the recombinant therapeutic product
      delivered. To mimic this clinical situation, we implanted microencapsulated
      recombinant cells producing human growth hormone into C57B1/6 mice to provoke
      antihuman growth hormone antibody production. We then investigated the efficacy
      of different immunosuppressive treatments to inhibit the development of
      neutralizing antibodies. The experimental mice were treated with either an
      immunosuppressive drug (FK506 or cyclophosphamide), a cytokine (interferon-gamma
      [IFN-gamma] or interleukin-12 [IL-12], or a monoclonal antibody (anti-CD4, anti
      gp39, or CTLA4-Ig). Serum human growth hormone and mouse anti-human growth
      hormone antibody levels were measured by enzyme-linked immunosorbent assay
      (ELISA) for 4 weeks. There were three patterns of response noted among the seven
      treatment groups. First, the mice receiving IFN-gamma, IL-12, anti-gp39, or CTLA4
      Ig were similar to the untreated controls-no suppression of anti-hGH antibodies
      and no improvement in delivery of hGH. Next, the mice receiving FK506 or
      cyclosphosphamide showed > or = 90% suppression of antibodies but also no
      improvement in product delivery. Last, the mice receiving anti-CD4 showed almost
      complete antibody suppression over 1 month postimplantation. Furthermore, only
      anti-CD4 permitted a sustained level of human growth hormone delivery to day 28,
      in contrast to the controls whose human growth hormone delivery was undetectable
      by day 14 postimplantation. Hence, the use of anti-CD4 inhibited formation of
      neutralizing antibodies against a recombinant gene product delivered in vivo, and
      allowed prolonged delivery of a foreign protein. Its role as adjunct treatment
      for appropriate patients receiving gene therapy should be examined further.

PMID- 9650613
TI  - Preclinical characterization of an anti-tat ribozyme for therapeutic application.
AB  - A hammerhead ribozyme retroviral construct, denoted RRz2, targeting the coding
      region of the human immunodeficiency virus type 1 (HIV-1) tat gene, has shown
      itself to be effective in a range of test systems. Inhibition of the replication
      of HIV-1 IIIB and primary drug-resistant strains in pooled transduced CEMT4 cells
      was consistently found to be more than 80% compared with the control-vector
      transduced cells, whereas a mutant RRz2 gave approximately 45% inhibition. A
      multiple HIV-1 passage assay showed the absence of emergence of mutations within
      the specific viral RNA ribozyme target sequences. This lack of generation of
      ribozyme "escape mutants" occurred despite the almost complete disappearance of a
      HIV-1 quasi-species in the testing virus. When RRz2 was tested in peripheral
      blood lymphocytes (PBLs) from HIV-1-infected patients, paired analysis showed
      that cell viability in the ribozyme-transduced HIV-1-infected PBLs was
      significantly higher than that in the vector-transduced cells. This difference in
      viability (vector versus RRz2) was not observed in PBLs from non-HIV-1-infected
      donors. Taken together, these results indicate that the transfer of an anti-HIV-1
      ribozyme gene into human T lymphocytes could have major impact on viral
      replication and T cell viability in the HIV-1-infected individual.

PMID- 9650614
TI  - Retrovirus-mediated in vivo gene transfer in the replicating liver using
      recombinant hepatocyte growth factor without liver injury or partial hepatectomy.
AB  - Retrovirus-mediated gene delivery into hepatocytes in vivo provides long-term
      gene expression, which is of great importance for treating most genetic and
      metabolic disorders. However, clinical application has not been realized because
      of the requirement for prior 70% partial hepatectomy or chemical (toxic) liver
      injury to initiate hepatocyte replication at the time of retroviral gene
      transduction. In this paper, we describe a novel gene delivery system that uses
      recombinant hepatocyte growth factor (rHGF) prior to retrovirus-mediated in vivo
      gene transfer in the liver without partial hepatectomy or liver injury. A single
      retroviral infusion through the portal vein following five systemic injections
      (via the tail vein) of 100 microg/kg rHGF resulted in a 10.4% 5-bromo-2'
      deoxyuridine (BrdU) labeling index (BLI) and 0.14% retroviral gene transduction
      efficiency (RGTE) in hepatocytes, which were 6.3- and 12.9-fold higher than those
      of controls, respectively. Modest additional increases in BLI and RGTE (13.4% and
      0.22%, respectively) were seen after five systemic injections of 500 microg/kg
      rHGF. The correlation between BLI and RGTE was statistically confirmed regardless
      of treatment. When rats received multiple retroviral infusions through a
      cannulated portal vein following five portal injections of 100 microg/kg rHGF,
      RGTE was dramatically increased (1.3%) and in some areas of the liver exceeded
      more than 10%. There was no evidence of liver injury in any animal. This approach
      has great potential for clinical application in terms of avoiding invasive
      procedures or liver injury.

PMID- 9650615
TI  - Interleukin-2 gene-modified allogeneic tumor cells for treatment of relapsed
      neuroblastoma.
AB  - Tumor cells that have been genetically modified to express immunostimulatory
      genes will induce effective antitumor responses in a range of syngeneic animal
      models. For human applications, transduced autologous tumor cell lines are often
      difficult or impossible to prepare, so that there are strong incentives for
      substituting a standardized allogeneic tumor cell line. However, such lines may
      be inferior immunogens if they differ from host tumors in the antigens they
      express. We have evaluated the safety, immunostimulatory, and antitumor activity
      of an interleukin-2-secreting allogeneic neuroblastoma cell line in 12 children
      with relapsed stage IV neuroblastoma. They received two to four subcutaneous
      injections of cells in a dose-escalating schedule, up to a maximum of 10(8) cells
      per injection. There was induration and pruritus at the injection site, and skin
      biopsies revealed mild panniculitis with CD3+ cells surrounding scanty residual
      tumor cells. There was a limited but significant peripheral monocytosis. No
      patient showed any increase in direct cytotoxic effector function against the
      immunizing cell line, but 3 patients had a rise in the frequency of neuroblastoma
      reactive cytotoxic T lymphocyte precursor cells. One child had > 90% tumor
      response (PR), 7 had stable disease, and 4 had progressive disease in response to
      vaccine alone. Although these results offer some encouragement for the continued
      pursuit of allogeneic vaccine strategies in human cancer, the antitumor immune
      responses we observed are inferior to those obtained in an earlier immunization
      study using autologous neuroblastoma cells. Hence, we suggest that this earlier
      approach remains preferable, its difficulties notwithstanding.

PMID- 9650616
TI  - Adenovirus-mediated transduction of intestinal cells in vivo.
AB  - The intestinal tract has many features that make it an attractive target for
      therapeutic gene transfer. In this study, replication-defective adenoviral
      vectors were used to explore parameters that may be important in administering
      gene therapy vectors to the intestine. After surgically accessing the intestine,
      an E1-, E3-deleted adenoviral vector encoding beta-galactosidase (beta-Gal) was
      directly injected into various regions of the small and large intestine of rats
      and rabbits. Significant transduction of the tissue was observed and
      histochemical staining was used to identify enterocytes as the primary targets of
      gene transfer. Expression of beta-Gal did not differ substantially when the virus
      was administered to the duodenum, ileum, or colon. When the vector was directly
      administered to segments of the distal ileum containing a Peyer's patch,
      transgene expression was approximately 10-fold higher than in segments lacking a
      Peyer's patch. In the Peyer's patches, a high level of expression was localized
      to epithelial cells, potentially M cells, overlying the lymphoid follicle domes.
      Transduction of these cells could have application in DNA-mediated oral
      vaccination. Administration of an adenoviral vector encoding a secreted alkaline
      phosphatase to the lumen resulted in expression and secretion of this gene
      product into the circulation. This finding demonstrates the potential of
      enterocytes to serve as heterotopic sites for the synthesis of heterologous gene
      products that would be secreted into the lumen of the intestinal tract or into
      the bloodstream.

PMID- 9650617
TI  - A novel three-pronged approach to kill cancer cells selectively: concomitant
      viral, double suicide gene, and radiotherapy.
AB  - Two obstacles limiting the efficacy of nearly all cancer gene therapy trials are
      low gene transduction efficiencies and the lack of tumor specificity. Recently, a
      replication-competent, E1B-attenuated adenovirus (ONYX-015) was developed that
      could overcome these limitations, because it was capable of efficiently and
      selectively destroying tumor cells lacking functional p53. In an attempt to
      improve both the efficacy and safety of this approach, we constructed a similar
      adenovirus (FGR) containing a cytosine deaminase (CD)/herpes simplex virus type-1
      thymidine kinase (HSV-1 TK) fusion gene, thereby allowing for the utilization of
      double-suicide gene therapy, which has previously been demonstrated to produce
      significant antitumor effects and potentiate the therapeutic effects of
      radiation. The FGR virus exhibited the same tumor cell specificity and
      replication kinetics as the ONYX-015 virus in vitro. Importantly, both the CD/5
      FC and HSV-1 TK/GCV suicide gene systems markedly enhanced the tumor cell
      specific cytopathic effect of the virus, and, as expected, sensitized tumor cells
      to radiation. By contrast, neither the FGR virus nor either suicide gene system
      showed significant toxicity to normal human cells. Both suicide gene systems
      could be used to suppress viral replication effectively, thereby providing a
      means to control viral spread. The results support the thesis that the three
      pronged approach of viral therapy, suicide gene therapy, and radiotherapy may
      represent a powerful and safe means of selectively destroying tumor cells in
      vivo.

PMID- 9650618
TI  - Human melanoma cells transfected with the B7-2 co-stimulatory molecule induce
      tumor-specific CD8+ cytotoxic T lymphocytes in vitro.
AB  - Neoplastic cells express tumor-associated antigens, but tumor rejection seldom
      occurs in vivo. The absence of an effective immune response may be explained by
      the inability of tumor cells to deliver co-stimulatory signals. Indeed,
      transfection of either B7-1 or B7-2 co-stimulatory molecules into mouse tumor
      cells enhances antitumor immune responses. In this study, we stably transfected
      human melanoma cells with the cDNA encoding the B7-2 molecule to evaluate in
      vitro: (i) the induction of anti-melanoma cytotoxic T lymphocytes (CTL) by
      stimulation of CD8+ T cells, purified from healthy donors and a melanoma patient,
      with B7-2 transfected allogeneic HLA-matched melanoma cells; (ii) the tumor
      specificity and the HLA restriction of the induced CTL; and (iii) the feasibility
      to propagate long-term antimelanoma CTL lines. We found that B7-2 transfected,
      but not untransfected or mock-transfected, melanoma cells activated MHC-class I
      restricted, melanoma-specific CD8+ CTL from healthy donors. More importantly,
      CD8+ tumor-associated lymphocytes, purified from a tumor-invaded lymph node of a
      melanoma patient and stimulated with B7-2-transfected melanoma cells, acquired a
      strong reactivity toward the autologous tumor. CTL lines with specific cytolytic
      activity could be propagated in long-term culture. These results indicate that:
      (i) the expression of the B7-2 molecule into human melanoma cells makes them
      immunogenic and able to act as antigen-presenting cells and (ii) purified CD8+
      cells, stimulated with B7-2+ allogeneic HLA-matched melanoma cells,
      preferentially recognize melanoma-specific rather than allogeneic antigens. This
      study may have clinical implications for passive and/or active immunotherapy in
      melanoma patients.

PMID- 9650619
TI  - Retroviral vector-mediated expression in primary human T cells of an endoplasmic
      reticulum-retained CD4 chimera inhibits human immunodeficiency virus type-1
      replication.
AB  - Intracellular expression of genes that inhibit key steps in the human
      immunodeficiency virus (HIV-1) replicative cycle could offer an alternative
      therapy for AIDS treatment. One of these approaches involves the inhibition of
      env protein maturation through the expression of CD4 molecules with added
      exogenous sequences that promote their retention in the endoplasmic reticulum
      (ER). We have tested this strategy using a CD4 chimera (CD4epsilon10) containing
      an ER retention sequence derived from the TCR CD3-epsilon chain. Transfection of
      CD4epsilon10 in the human T cell line Jurkat made it resistant to infection with
      two different HIV-1 isolates, which was evaluated by measuring p24 antigen
      production, induction of apoptosis, and syncytia formation. Furthermore,
      polymerase chain reaction (PCR) analysis of genomic DNA showed no traces of the
      proviral HIV-1 genome in CD4epsilon10-transfected cells, suggesting it was not
      maintained latently in these cells. To facilitate the delivery of the
      CD4epsilon10 chimera to primary cells from AIDS patients, a Moloney-based
      retroviral vector was constructed that expresses CD4epsilon10 under the
      transcriptional control of the HIV-1 long terminal repeat (LTR) promoter.
      Transduction of the MT-2 human T cell line with this vector rendered it resistant
      to infection with HIV-1 by a process that involved the inhibition of gp160
      proteolytic processing. Finally, transduction of the CD4epsilon10 chimera into T
      lymphoblasts derived from asymptomatic HIV-infected individuals demonstrated a
      protective effect, resulting in both an increased cellular proliferation rate and
      an increased percentage of CD4+ cells. These results suggest that it is feasible
      to use retroviral transduction of CD4epsilon10 as a gene therapy approach for
      AIDS treatment.

PMID- 9650620
TI  - Corrective transduction of human epidermal stem cells in laminin-5-dependent
      junctional epidermolysis bullosa.
AB  - Laminin-5 is composed of three distinct polypeptides, alpha3, beta3, and gamma2,
      which are encoded by three different genes, LAMA3, LAMB3, and LAMC2,
      respectively. We have isolated epidermal keratinocytes from a patient presenting
      with a lethal form of junctional epidermolysis bullosa characterized by a
      homozygous mutation of the LAMB3 gene, which led to complete absence of the beta3
      polypeptide. In vitro, beta3-null keratinocytes were unable to synthesize laminin
      5 and to assemble hemidesmosomes, maintained the impairment of their adhesive
      properties, and displayed a decrease of their colony-forming ability. A
      retroviral construct expressing a human beta3 cDNA was used to transduce primary
      beta3-null keratinocytes. Clonogenic beta3-null keratinocytes were transduced
      with an efficiency of 100%. Beta3-transduced keratinocytes were able to
      synthesize and secrete mature heterotrimeric laminin-5. Gene correction fully
      restored the keratinocyte adhesion machinery, including the capacity of proper
      hemidesmosomal assembly, and prevented the loss of the colony-forming ability,
      suggesting a direct link between adhesion to laminin-5 and keratinocyte
      proliferative capacity. Clonal analysis demonstrated that holoclones expressed
      the transgene permanently, suggesting stable correction of epidermal stem cells.
      Because cultured keratinocytes are used routinely to make autologous grafts for
      patients suffering from large skin or mucosal defects, the full phenotypic
      reversion of primary human epidermal stem cells defective for a structural
      protein opens new perspectives in the long-term treatment of genodermatoses.

PMID- 9650621
TI  - Human immunodeficiency virus type 2 lentivirus vectors for gene transfer:
      expression and potential for helper virus-free packaging.
AB  - In addition to the long-term expression of the transgene provided by all
      retroviral vectors, lentiviruses present the opportunity to transduce nondividing
      cells and potentially achieve regulated expression. The development of lentiviral
      vectors requires the design of transfer vectors to ferry the transgene with
      efficient encapsidation of the transgene RNA and with full expression capability,
      and of a packaging vector to provide packaging machinery in trans but without
      helper virus production. For both vectors, a knowledge of packaging signal is
      required-the signal to be included in the transfer vector but excluded from the
      packaging vector. Among the human lentiviruses, human immunodeficiency virus type
      1 and type 2 (HIV-1 and HIV-2), we think HIV-2 is better suited for gene transfer
      than HIV-1. It is less pathogenic and thus safer during design and production;
      its desirable nuclear import and undesirable cell-cycle arrest functions are
      segregated on two separate genes. In HIV-1 infection, it is less likely to
      recombine with the resident HIV-1, and it may itself downregulate HIV-1
      expression. Evidently, elements located both upstream and downstream of the
      splice donor site in the leader sequence participated in RNA encapsidation and
      these sequences appeared necessary and sufficient. Deletion of both sequence
      elements resulted in a dramatic curtailment of RNA encapsidation and helper virus
      production. This was accompanied by some but acceptable loss of gene expression
      capability. The helper virus-free phenotype and expression capability of the
      double mutant was maintained upon replacement of its 3' long terminal repeat with
      a minigene cassette containing a transcriptional termination signal and a drug
      resistance marker gene. Deletion of the splice donor site itself had a dramatic
      negative effect on gene expression, supporting the important role of this element
      in the life of RNA.

PMID- 9650622
TI  - Redox gene therapy protects human IB-3 lung epithelial cells against ionizing
      radiation-induced apoptosis.
AB  - Toxicity to nontumor-derived tissue has proven to be a significant obstacle in
      achieving therapeutic levels of gamma irradiation in the treatment of cancer. The
      formation of reactive oxygen species (ROS) such as superoxide radicals (O2-)
      following irradiation is thought to be a major determinant of cellular damage. To
      this end, we describe the generation of two recombinant adenoviral vectors
      expressing the radical-scavenging enzymes MnSOD and CuZnSOD to test therapeutic
      strategies of radioprotection. Using a human lung epithelial cell line (IB-3), we
      have demonstrated that infections with both Ad.CMVMnSOD or Ad.CMVCuZnSOD
      significantly increase both the levels of SOD protein and enzymatic activity as
      compared to control cells. This increase in SOD expression reduced the level of
      apoptosis at 72 hr post-irradiation by 50% as compared to mock- or Ad.CMVLacZ
      infected cells. Such studies provide the foundation for radioprotective gene
      therapies in the treatment of cancer.

PMID- 9650623
TI  - Effects of reward and response cost on response inhibition in AD/HD, disruptive,
      anxious, and normal children.
AB  - In previous research, children with attention deficit/hyperactivity disorder
      (AD/HD) have demonstrated impaired response inhibition on the stop paradigm. In
      this study we examined whether this impairment in fact reflects a motivational
      deficit. Four groups of children (age range 7-13 years) participated in the
      study: 14 AD/HD children, 21 normal controls, 14 disruptive children, and 14
      anxious children. The psychopathological groups were recruited from special
      educational services and mental health outpatient clinics. Parent, teacher, and
      child questionnaires were used to select children with pervasive disorders.
      Normal controls attended regular classes and scored low on all questionnaires.
      Children were tested once with reward contingencies and once with response cost
      contingencies in a randomized cross-over design. We hypothesized that if a
      motivational deficit underlies poor response inhibition in AD/HD children, this
      deficit will be remedied by response contingencies. Despite the presence of
      response contingencies, AD/HD children showed poor response inhibition compared
      with normal controls. Findings argue against a motivational explanation for the
      response inhibition deficit in AD/HD children.

PMID- 9650624
TI  - Social anxiety in children with anxiety disorders: relation with social and
      emotional functioning.
AB  - Investigated the psychometric properties of the Social Anxiety Scale for children
      Revised (SASC-R) as well as relations between social anxiety and children's
      social and emotional functioning. Participants were a clinic sample of children,
      ages 6-11 with anxiety disorders (N = 154) who completed the SASC-R. For a subset
      of these children, parent ratings of social skills, and self-ratings of perceived
      competence and peer interactions were also obtained. Factor analysis of the SASC
      R supported the original three-factor solution and internal consistencies were in
      the acceptable range. Among children with simple phobia, scores on the SASC-R
      differentiated those with and without a comorbid social-based anxiety disorder.
      Social anxiety was also associated with impairments in social and emotional
      functioning. Specifically, highly socially anxious children reported low levels
      of social acceptance and global self-esteem and more negative peer interactions.
      Girls with high levels of social anxiety were also rated by parents as having
      poor social skills, particularly in the areas of assertive and responsible social
      behavior.

PMID- 9650625
TI  - Assessing culturally different students for attention deficit hyperactivity
      disorder using behavior rating scales.
AB  - Behavior rating scales are commonly used in the assessment of attention deficit
      hyperactivity disorder (ADHD). However, there is little information available
      concerning the extent to which scales are valid with culturally different
      students. This study explored the use of the ADHD-IV Rating Scale School Version
      with male Caucasian (CA) and African American (AA) students from ages 5 to 18
      years. Teachers rated AA students higher on all symptoms across all age groups.
      LISREL analysis indicated that scale does not perform identically across groups.
      This was supported by the results of multidimensional scaling with suggested that
      there is a different relation between items across groups. Implications for
      research and practice are discussed.

PMID- 9650626
TI  - Moderators and mediators of the effects of interparental conflict on children's
      adjustment.
AB  - Moderational and mediational models of the relationships among appraisals,
      interparental conflict, and children's adjustment were tested in a sample of 174
      families with a school-age child. Parents rated children's exposure to
      interparental conflict and internalizing, externalizing, and total behavior
      problems. Children completed questionnaires regarding their appraisals of their
      parents' conflicts, including frequency and intensity, perceived threat, control,
      and self-blame, as well as measures of anxiety and depression. Results overall
      demonstrated more consistent support for the moderational than mediational
      hypotheses. Appraisals of conflict properties, threat, self-blame, and perceived
      control moderated the effects of interparental conflict on externalizing, total
      problems, and anxiety in boys. Conflict properties, threat, self-blame, perceived
      control, and self-calming acted as moderators of internalizing in girls.

PMID- 9650627
TI  - Cross-informant agreement in the assessment of social phobia in youth.
AB  - In the present study involving children and adolescents with a principal
      diagnosis of social phobia, we measured parent-child agreement regarding social
      anxiety symptoms. Additionally, we examined variables related to the severity of
      the children's social phobia symptoms as reported by children and as rated by
      clinicians. Examination of cross-informant agreement indicated little difference
      between mean parent and children ratings of the children's social fears. In
      contrast, there was a significant difference in parent and children ratings of
      the children's avoidance, with parents endorsing greater degrees of social
      avoidance. Children's report of social avoidance was negatively related to scores
      on a measure of self-presentational concerns (i.e., social desirability).
      Clinicians' determination of the severity of the children's social phobia was
      also influenced by the children's self-presentation as well as parent report of
      social avoidance and children's depression scores. Thus, this differential
      weighting by the clinician of parent versus child report may be related to the
      finding that children's self-reported social avoidance was negatively related to
      their concerns regarding positive self-presentation. Results suggest the need to
      consider the impact of social desirability when examining clinical
      characteristics of children and adolescents with social phobia.

PMID- 9650629
TI  - Alcohol drinking and blood pressure among adolescents.
AB  - The purpose of this study was to evaluate alcohol consumption among adolescents
      from Tucuman, Argentina, and to determine its possible relationship with
      increased levels of blood pressure. Three hundred fifty-six students aged 13-18
      included in the study were asked to answer questionnaires anonymously. Two blood
      pressures measures were then taken. Differences between both sexes were found in
      quantity and frequency of alcohol consumption. Enjoyment was determined to be the
      main reason for drinking. There was an association between frequency and alcohol
      related problems, and smoking habits. There were also differences in blood
      pressure among males and females. A weak, but significant, relationship between
      quantity/frequency index and diastolic blood pressure was found. A greater
      prevalence of hypertension in male heavy drinkers was noted as well. Because this
      addiction implies multiple social problems and it also accounts for a
      hypertension risk factor, the importance of aiming at developing prevention
      strategies for alcohol abuse among adolescents is stressed.

PMID- 9650628
TI  - Comorbidity of conduct and depressive problems at sixth grade: substance use
      outcomes across adolescence.
AB  - The comorbidity of conduct and depressive problems and substance use outcomes
      were examined in a community-based sample of 340 African American males and
      females. Alcohol, tobacco, and marijuana use were examined at Grades 6, 8, and 10
      based on the following group membership at sixth grade: (a) comorbid conduct and
      depressive problems; (b) conduct problems only; (c) depressive problems only; (d)
      neither conduct nor depressive problems. Overall, the two conduct problem groups
      displayed the highest levels of substance use, although at some time points,
      comorbid youth displayed significant higher substance use levels. Subjects with
      depressive problems only displayed levels of substance use that were equivalent
      to subjects in the nonproblem group. Results highlight the importance of
      controlling for comorbid symptoms, possible interactive effects between conduct
      and depressive problems, and implications for treatment and prevention of
      substance use.

PMID- 9650630
TI  - Relative and combined effects of ethanol and protein deficiency on zinc, iron,
      copper, and manganese contents in different organs and urinary and fecal
      excretion.
AB  - The relative contribution of protein deficiency to the altered metabolism of
      certain trace elements in chronic alcoholics is not well defined, so this study
      was performed to analyse the relative and combined effects of ethanol and protein
      deficiency on liver, bone, muscle, and blood cell content of copper, zinc, iron,
      and manganese, and also on serum levels and urinary and fecal excretion of these
      elements in four groups of eight animals each that were pair-fed during 8 weeks
      with a nutritionally adequate diet, a 36% (as energy) ethanol-containing
      isocaloric diet, a 2% protein isocaloric diet, and a 36% ethanol 2% protein
      isocaloric diet, respectively, following the Lieber-DeCarli model. Five
      additional rats were fed ad lib the control diet. Protein malnutrition, but not
      ethanol, leads to liver zinc depletion. Both ethanol and protein malnutrition
      cause muscle zinc depletion and increase urinary zinc and manganese excretion,
      whereas ethanol also increases urinary iron excretion and liver manganese
      content. No differences were observed regarding copper metabolism.

PMID- 9650631
TI  - Altered ambient temperature and ethanol-induced conditioned place preference in
      mice.
AB  - Previous studies with rats exposed to altered ambient temperature (Ta) or with
      mice selectively bred for their thermal response to ethanol have shown that a
      reduced hypothermic response is correlated with decreased place aversion and
      greater place preference, respectively. The present experiment was designed to
      test whether alterations in Ta would alter ethanol's ability to produce
      conditioned place preference in genetically heterogeneous mice. Three groups of
      mice underwent a differential conditioning procedure that paired one distinctive
      floor texture with ethanol (2.25 g/kg, i.p.) and a different floor texture with
      saline. During conditioning, each group was exposed to a different Ta: cold (10
      degrees C), normal (21 degrees C), or warm (34 degrees C). Each group was further
      divided and subgroups were tested for preference at either the conditioning
      temperature or a different temperature. Consistent with previous findings, mice
      conditioned and tested at normal Ta developed a conditioned preference for the
      ethanol-paired floor. In contrast, mice exposed to a warm or cold Ta during
      conditioning or testing failed to show place conditioning. Although exposure to
      either warm or cold Ta interfered with place conditioning, only the warm Ta had
      an effect on hypothermia. These findings suggest that altered Ta produced stimuli
      that may have interfered with the association between floor cues and ethanol
      during conditioning or interfered with expression of this association during
      testing.

PMID- 9650632
TI  - Splenic sympathetic response to endotoxin is blunted in the fetal alcohol-exposed
      rat: role of nitric oxide.
AB  - This study was designed to test the hypothesis that nitric oxide (NO) mediates
      the blunted splenic sympathetic response to lipopolysaccharide (endotoxin) that
      occurs in young rats exposed to alcohol in utero (FAE). The subjects, 26-29-day
      old rats, were progeny of pregnant dams fed an alcohol diet (35% of the calories
      were derived from ethanol) or their control and pair-fed (PFC) cohorts. We
      examined the effects of lipopolysaccharide (LPS) (0.5 mg/kg, i.p.) on splenic
      norepinephrine (NE) turnover, an index of sympathetic neural activity, splenic
      inducible NO synthase (iNOS) protein immunoreactivity, and NO metabolites
      nitrite/nitrate concentrations in plasma. In response to LPS, splenic NE turnover
      was increased by more than twofold in the PFC groups, but the increase did not
      occur in their FAE cohorts. The blockade of NOS with L-NAME (30 mg/kg, i.p.)
      reversed this difference. In both the PFC and FAE rats, basal levels of splenic
      iNOS protein immunoreactivity were equally barely detected and plasma NO
      metabolite levels were relatively low (25 microM in both groups). In response to
      LPS, however, iNOS protein displayed a marked increase in the PFC group and an
      even greater increase (by close to threefold) in the FAE rats. LPS also
      substantially increased plasma NO metabolite levels by close to eightfold in the
      control groups, but by 15-fold in their FAE cohorts compared to the basal levels.
      These findings support the hypothesis that in the FAE rat, an augmented NO
      formation accounts for the blunted sympathetic response to endotoxin.

PMID- 9650633
TI  - Pyrrolidine dithiocarbamate attenuates alcohol-induced leukocyte-endothelial cell
      interaction and cerebral vascular damage in rats: possible role of activation of
      transcription factor NF-kappaB in alcohol brain pathology.
AB  - Effects of chronic (14-day) pretreatment of orally administered pyrrolidine
      dithiocarbamate (PDTC) (100 or 200 mg/kg/day) on alcohol-induced venular
      cerebrovasospasm, microvessel rupture, leukocyte-endothelial chemoattraction, and
      microhemorrhaging was studied by direct, quantitative in vivo high-resolution TV
      microscopy of the intact rat brain. Sham animals chronically treated with placebo
      exhibited concentration-dependent venular cerebrovasospasm, endothelial-leukocyte
      rolling and attraction, microvessel rupture. and focal hemorrhages, irrespective
      of route (i.e., perivascular, systemic) of ethanol administration. PDTC
      pretreatment either prevented or ameliorated greatly the cerebrovasospasm,
      leukocyte-endothelial chemoattraction, and brain vascular damage induced by
      ethanol. These new data suggest that alcohol induces cerebral vascular and brain
      damage by reperfusion injury events, which trigger induction of proinflammatory
      factors, and transcription factor NF-kappaB and lipid peroxidation of vascular
      smooth muscle and endothelial cell membranes; these proinflammatory, pro-oxidant,
      and redox events could play a crucial role in the pathogenesis of alcohol-induced
      cerebral ischemia and stroke.

PMID- 9650634
TI  - The D2 dopamine receptor gene: a review of association studies in alcoholism and
      phenotypes.
AB  - The role of the D2 dopamine receptor (DRD2) gene in alcoholism and other
      substance use disorders has come under intense investigation since the minor TaqI
      A (A1) allele of the DRD2 gene was first reported to be associated with
      alcoholism. In a meta-analysis of 15 US and international studies of European
      (non-Hispanic) Caucasians, consisting of 1015 alcoholics (more severe and less
      severe) and 898 controls (unassessed and assessed for alcoholism), alcoholics had
      a higher prevalence (p < 10(-7)) and frequency (p < 10(-5)) of the A1 allele than
      controls. The prevalence of the A1 allele was 1.5-fold higher in more severe than
      less severe alcoholics (p < 10(-4)), whereas unassessed controls had a twofold
      higher prevalence of the A1 allele than assessed controls (p < 10(-4)). Whereas
      more severe alcoholics had a threefold higher A1 allelic prevalence than assessed
      controls (p < 10(-10)), A1 allelic prevalence was virtually identical in less
      severe alcoholics and in unassessed controls. The A1 allele has also been
      associated with other drug problems including cocaine, nicotine, and
      polysubstance abuse. Furthermore, the minor TaqI B (B1) allele of the DRD2 gene
      has been associated with alcoholism and psychostimulant (cocaine, amphetamine)
      abuse. Beyond association studies, phenotypic differences exist between genotypes
      containing the TaqI A minor (A1A1 and A1A2) and major (A2A2) alleles of the DRD2.
      These different phenotypes have been identified through a number of approaches,
      including pharmacological, neurophysiological, neuropsychological, stress,
      personality, metabolic, and treatment studies. In conclusion, the present review
      suggests that the type of alcoholics and the nature of controls used are among
      critical factors in DRD2 association studies in alcoholism. Intronic mutations in
      both the 3'(TaqI A) and 5'(TaqI B) regions of the DRD2 associate with alcoholism
      and other drug use disorders. The identification of phenotypes of DRD2 genotypes
      suggests that the observed intronic DRD2 mutations may have functional
      consequences that predispose individuals to a variety of substance use disorders.

PMID- 9650635
TI  - A functionally deficient DRD2 variant [Ser311Cys] is not linked to alcoholism and
      substance abuse.
AB  - Association studies with the DRD2 Taq1A marker have been variable in implicating
      DRD2 as a "Reward Deficiency Syndrome Gene" for alcoholism and substance abuse.
      Given that the Taq1A marker is not functionally significant, second-generation
      studies on the DRD2 receptor to identify functional variants and evaluate their
      effect on the phenotype are the logical step towards confirming and extending the
      DRD2 hypothesis. This article discusses the implications and process of progress
      made in these directions. The new findings are the description of structural
      variants in the D2 receptor, the demonstration that one of these, Ser311Cys,
      largely prevents signal transduction following receptor activation and the use of
      Ser311Cys in a large association and sib-pair linkage anlysis in an American
      Indian isolate. In this particular population, the Cys311 variant is far more
      abundant (0.16) than in Caucasians (0.03). Genotyping of Ser311Cys, the DRD2
      intron 2 STR, and the Taq1A marker in 459 subjects, including 373 sib-pairs and
      15 Cys311/Cys311 homozygous individuals, revealed no association to alcoholism,
      substance use disorders, or schizophrenia. The implication is that a DRD2 variant
      that dramatically impairs receptor function was not sufficient to significantly
      alter alcoholism vulnerability in a relatively large and also genetically and
      environmentally homogeneous sample.

PMID- 9650636
TI  - Alternative strategies for uncovering genes contributing to alcoholism risk:
      unpredictable findings in a genetic wonderland.
AB  - In spite of technological advances in genetic mapping, the field of alcoholism
      genetics has had few findings that could be confirmed. Possible sources for the
      largely negative results and suggested ways for improving the search for genes
      contributing to alcoholism risk are discussed. These include the choice of
      phenotype to be studied, whether narrow or broad, whether only mild or severe
      forms are included, and whether or not comorbidity should be excluded. The
      ascertainment schema for selecting families utilized in our laboratory which
      results in an especially high recurrence risk will be discussed with respect to
      finding candidate genes. The complexity of the alcoholism phenotype will be
      discussed with respect to the existence of phenocopies, genetic heterogeneity,
      and the difficulties associated with defining the disorder in a way that covers
      all ages and both genders adequately. Finally, the equivocal results found for
      the D2 dopamine receptor are discussed with respect to current data analytic
      techniques, which emphasize affected sib-pairs, techniques that may be especially
      problematic for a disorder such as alcoholism that has marked tendencies for
      phenocopies to arise.

PMID- 9650637
TI  - Why different rules are required for polygenic inheritance: lessons from studies
      of the DRD2 gene.
AB  - In 1990 Blum, Noble and coworkers reported a significant association between the
      1 allele of the Tarq1A polymorphism of the D2 dopamine receptor gene (DRD2) and
      severe alcoholism. Subsequently, some reports using both linkage and association
      techniques supported this finding whereas others either did not, or seemed not to
      support this association. Although some of the controversy is due to true
      variability in the frequency of the D2A1 allele in different groups of alcoholics
      and controls, some is also due to the frequent attempt to apply the rules of
      single-gene disorders to what is in all likelihood a multifactorial, polygenic
      disorder. When the rules that are appropriate to polygenic inheritance are used a
      significant portion of the controversy is resolved. Those rules, and their
      application to the role of the DRD2 gene in addictive, impulsive behaviors, are
      reviewed.

PMID- 9650638
TI  - Issues and strategies in the genetic analysis of alcoholism and related addictive
      behaviors.
AB  - Research into the genetics of alcoholism susceptibility and related behaviors has
      become highly contentious for a number of reasons: at issue is the identification
      of factors that may ultimately determine human behaviors, the limitations of the
      technologies being used to conduct relevant studies have not been assessed
      exhaustively, and independent studies have produced widely different results.
      Addressing these and other questions of relevance in the dissection of the
      genetic basis of alcoholism susceptibility will be nothing if not difficult. In
      this article, we consider issues related to one not-so-minor research angle being
      used more and more in investigations of alcoholism and related disorders: the
      identification of susceptibility loci through the use of anonymous (or seemingly
      anonymous) DNA markers. We also consider issues that might promote (or resist)
      the reconcilability of independent study results, and describe some basic
      strategies that might help make study results more compelling in light of the
      complexity of alcoholism and related behaviors.

PMID- 9650639
TI  - Molecular genetics of alcoholism and other addiction/compulsive disorders.
      General discussion.

PMID- 9650640
TI  - Cadmium and calcium-dependent c-fos expression in mesangial cells.
AB  - Cadmium is a carcinogenic metal known to increase the expression of several
      protooncogenes in a variety of cells. although the underlying mechanisms are
      unknown. Renal mesangial cells are smooth muscle cells in which Ca2+ signaling
      pathways regulate the induction of c-fos through both cAMP-dependent and mitogen
      activated protein kinase- (MAPK-) dependent pathways. We report that c-fos is
      induced in these cells by both protein kinase C- (PKC-) dependent (phorbol ester,
      platelet-derived growth factor), and independent (serum, ionomycin) mechanisms.
      In all cases, prevention of an increase in cytosolic [Ca2+] with the chelator
      BAPTA prevented this induction. CdCl2 (10 microM) caused an accumulation of c-fos
      mRNA over 30 min that was sustained for at least 8 h. Cycloheximide inhibits
      turnover of c-fos mRNA and shows a synergistic effect with Cd2+ on transcript
      levels. Together with a similar half life of the transcript whether accumulated
      in response Cd2+ or induced by phorbol ester, this suggests induction of c-fos by
      Cd2+ rather than an effect of Cd2+ on transcript stability. Cadmium increased
      MAPK activity by 5 min; this was sustained for at least 8 h, consistent with the
      time course of c-fos mRNA accumulation. The MAPK kinase inhibitor PD98059 caused
      a marked decrease in the induction of c-fos by Cd2+, but did not eliminate the
      phenomenon completely. Although Cd2+ has been reported to activate PKC in vitro,
      no effect was found on PKC activity in Cd2+ -treated cells, indicating the
      activation of MAPK by Cd2+ is through an unidentified PKC-independent pathway. We
      conclude that Cd2+ can cause a sustained induction of c-fos in part through
      sustained activation of MAPK, that contrasts with the transient activation of
      these species in response to physiological mitogenic stimuli.

PMID- 9650641
TI  - Effect of calmodulin-inhibitors and verapamil on the nephrotoxicity of cadmium in
      rat.
AB  - Recent reports indicate that calmodulin inhibitors (CIs) can modify cadmium (Cd)
      toxicity in rodents. Pretreatment with CIs prevents Cd-induced testicular damage
      in mice and reduces the severity of such damage in rats. On the other hand it has
      been suggested that the cellular transport of Cd can be partly inhibited by the
      calcium-channel inhibitor, verapamil. The aim of this study was to determine
      whether these inhibitors can prevent the toxic effects of Cd on the kidney which
      is the critical organ. For that purpose, we have examined the effects of two CIs
      (trifluoperazine and chlorpromazine) and of verapamil on the development of
      tubular damage in female Sprague-Dawley rats. The animals were injected
      subcutaneously 5 days a week for 8 weeks with cadmium chloride (1 mg Cd/kg),
      alone or in association with trifluoperazine (20 mg/kg), chlorpromazine (15
      mg/kg) or verapamil (2 x 5 mg/kg). The development of renal dysfunction was
      followed by measuring the urinary excretion of the low molecular weight protein
      Clara cell protein (CC16). In Cd-treated rats, the urinary excretion of CC16
      started to increase from week 6 to reach at the end of experiment values more
      than 100-times above normal. CIs or verapamil did not influence the rise of
      urinary CC16 induced by Cd. The three inhibitors, by contrast, enhanced the
      accumulation of Cd in the liver and, at the exception of chlorpromazine, in the
      kidneys of Cd-treated rats. Although interfering with the metabolism of Cd, CIs
      and verapamil do not prevent renal damage in rats chronically exposed to this
      heavy metal.

PMID- 9650642
TI  - Effect of cocaine, 95% oxygen and ellagic acid on the development and antioxidant
      status of cultured rat embryos.
AB  - Prenatal exposure to cocaine has been associated with adverse developmental
      effects and current data suggest cocaine induced malformations are caused by
      ischemic-reperfusion injury. This study was undertaken to assess a new in vitro
      model which uses a routine rat whole embryo culture system that incorporates a
      change in oxygen status, and to examine the effects of altered oxygen status and
      pretreatment with ellagic acid (EA), an anti-oxidant, after cocaine exposure.
      Embryos were evaluated by determining a developmental score and by measuring
      tissue reduced glutathione (GSH) levels. Following re-oxygenation with 95% O2 for
      the last 6 h of culture, embryos treated with cocaine had reduced developmental
      scores and GSH levels. Embryos treated with cocaine and not re-oxygenated with
      95% O2 did not have reduced developmental scores. EA blocked the effects of
      cocaine on developmental score and GSH level. These data support ischemia
      reperfusion injury as the mechanism of cocaine developmental toxicity.

PMID- 9650643
TI  - Hepatoprotective activity of thymoquinone in isolated rat hepatocytes.
AB  - Thymoquinone, the active constituent of Nigella sativa, was tested in isolated
      rat hepatocytes as a hepatoprotective agent against tert-butyl hydroperoxide
      (TBHP) toxicity. TBHP (2 mM) was used to produce oxidative injury in isolated rat
      hepatocytes and caused progressive depletion of intracellular glutathione (GSH),
      loss of cell viability as evidenced by trypan blue uptake and leakage of
      cytosolic enzymes, alanine transaminase (ALT) and aspartic transaminase (AST).
      Preincubation of hepatocytes with 1 mM of either thymoquinone or silybin, which
      is a known hepatoprotective agent, resulted in the protection of isolated
      hepatocytes against TBHP induced toxicity evidenced by decreased leakage of ALT
      and AST, and by decreased trypan blue uptake in comparison to TBHP treated
      hepatocytes. Both thymoquinone and silybin prevented TBHP induced depletion of
      GSH to the same extent. Although thymoquinone protected the liver enzymes
      leakage, the degree of protection was less than that caused by silybin.

PMID- 9650644
TI  - Cypermethrin increases apo A-1 and apo B mRNA but not hyperlipidemia in rats.
AB  - The hepatotoxic effect of cypermethrin and the expression of hepatic genes at the
      mRNA level, as molecular markers of liver damage, were evaluated in rats
      following exposure to cypermethrin. The expression of hepatic genes was compared
      with conventional liver functional tests, and correlations were made by studying
      the liver at the ultrastructural level. Cypermethrin treated rats presented a
      significant decrease, of 79% and 22%, on the expression of albumin and apo E
      genes at 5 days, respectively. The levels of apo A-1 and apo B mRNA were
      increased up to four- and fivefold, respectively. This increase did not correlate
      with the serum values of HDL and VLDL lipoprotein particles. Intracytoplasmic
      lipid droplets were observed after the first 2 days following cypermethrin
      administration, suggesting that apo A-1 and B mRNA were translated but not
      secreted. There were significant correlations between the low values of the
      albumin gene expression, the decrease in the HDL concentrations, and the
      ultrastructural alterations, respectively. These alterations were mainly a large
      amount and increased size of mitochondria in the animals exposed to cypermethrin.
      It is concluded that under the experimental conditions used, cypermethrin may
      alter the metabolism of lipids and proteins in rat liver.

PMID- 9650645
TI  - Toxicokinetics of trimethyltin in four inbred strains of mice.
AB  - Sixteen week old male AKR/J, Balb/cByJ, C57B1/6J and DBA/2J mice received single
      i.p. injections of trimethyltin (TMT). The toxic effects were weight loss,
      hyperexcitability, tremor, clonic-tonic convulsion, posterior paresis and death.
      The minimum toxic dose was 1.8 mg/kg, for the AKR strain and 2.3 mg/kg for the
      other strains. The highest non-lethal dose was 2.7 mg/kg for the AKR, DBA/2 and
      C57B1/6 strains and 3.0 mg/kg for the Balb/c strain. Blood levels of TMT peaked
      within 1 h and declined with half-lives of approximately 1.5 days. Blood levels
      of TMT were lower in the C57B1/6 mice due to greater tissue binding of TMT in
      C57B1/6 mice. Some of the toxic endpoints showed different rank orders among the
      strains, leading us to conclude that more than one biological process is
      responsible for the acute toxic effects of TMT in mice.

PMID- 9650646
TI  - Protein oxidation biomarkers in hyperoxic lung injury in rats: effects of U
      74389.
AB  - Hyperoxia, used therapeutically in the treatment of respiratory insufficiencies,
      can cause lung injury, probably through the actions of reactive oxygen species.
      The present studies were designed to test the hypothesis that oxidation of
      specific proteins would provide useful biomarkers of the onset of tissue injury,
      and thereby provide clues as to the mechanisms responsible. We exposed adult male
      Sprague-Dawley rats to room air or to greater than 95% O2 for 60 h and examined
      proteins in pleural effusion and broncho-alveolar lavage (BAL) fluids, and in
      lung tissue homogenates and subfractions. Oxidation of protein thiols was
      assessed by derivatization with monobromobimane, separation by electrophoresis,
      and visualization of the fluorescent thioether derivatives. Derivatization with
      2,4-dinitrophenylhydrazine (DNPH), electrophoresis, and western analysis was
      employed to assess a different class of oxidative modifications, frequently
      termed 'protein carbonyls'. In addition, we investigated the effects of the 21
      aminosteroid U-74389G, 10 mg/kg, given intraperitoneally every 12 h, on
      biomarkers of protein oxidation and on manifestations of lung injury. Hyperoxia
      caused lung injury evidenced by pleural effusions, increases in BAL protein
      concentrations, and pulmonary edema; U-74389G attenuated the first two indices of
      lung injury, but did not alter edema. Protein thiol status of the fractions
      studied were not affected notably by hyperoxia, or by the aminosteroid. The
      formation of DNPH-reactive sites on a limited number of proteins by hyperoxia was
      observed, and some of these effects were attenuated in the animals given U
      74389G. Histological examination of lung tissues showed accumulation of intra
      alveolar protein exudates in hyperoxic rats, and a significant attenuation of
      this effect was observed in the animals treated with U-74389G. In conclusion,
      studies of shifts in protein thiol status that may be caused by hyperoxia will
      require increasingly specific methods of analysis, and characterization of the
      specific DNPH-reactive proteins formed in hyperoxia may provide critical insights
      into the mechanisms of lung injury. Administration of U-74389G offers some degree
      of protection against hyperoxia and attenuation of these biomarkers of oxidation,
      but the precise mechanisms by which this protection is effected will require
      additional study.

PMID- 9650647
TI  - The experimental toxicology of tramadol: an overview.
AB  - The experimental toxicological findings of tramadol are reviewed and discussed.
      Tramadol is a centrally acting analgesic. In acute toxicity studies, LD50 values
      are estimated to be around 300-350 mg/kg body weight (rat, mouse, oral
      administration). After intravenous administration the LD50 values ranged from 50
      to 100 mg/kg body weight. In subacute and chronic toxicity studies, clinical
      signs of intoxication are mainly behavioural disorders and convulsions, beginning
      at dose levels of 25 mg/kg. Clinical pathological alterations or morphological
      lesions, in particular neuropathological findings were not detected. Overall, the
      battery of mutagenicity studies shows no evidence of a genotoxic risk to man.
      Reproductive and developmental toxicity investigations and carcinogenicity
      studies were without substance-dependent findings. Toxicological and
      toxicokinetical data of both enantiomers did not show biologically relevant
      deviations in comparison to the data on tramadol. The toxicological
      characteristic of this compound is demonstrated.

PMID- 9650648
TI  - Therapeutic amnioinfusions and fetal fibronectin pattern in a case with preterm
      ruptured membranes that resealed.
AB  - OBJECTIVE: Determination of fetal fibronectin (fFN) levels in a patient at risk
      of preterm delivery and having premature rupture of the membranes. PATIENT AND
      METHODS: The present case report concerns a pregnant woman with premature rupture
      of the membranes at 16 weeks of gestation who was submitted to repeated
      therapeutic transabdominal amnioinfusions and had a spontaneous resolution of the
      rupture at 32 weeks of gestation. RESULTS: A good pregnancy outcome was observed.
      High cervicovaginal fFN levels were observed during the period of membrane
      rupture with following drop of fFN levels during this period and spontaneous
      reseal of the membranes. CONCLUSIONS: Active expectant management, using repeated
      amnioinfusions, probably played a useful role in the therapeutic success of this
      pregnancy. Further, fFN was a reliable marker of the rupture of membranes. The
      possible role of fFN in the clinical management of high-risk pregnancies is
      confirmed.

PMID- 9650649
TI  - Prenatal diagnosis of cloacal dysgenesis sequence: differential diagnosis from
      other forms of fetal obstructive uropathy.
AB  - Cloacal dysgenesis sequence (CDS) is a rare cause of fetal obstructive uropathy
      (FOU). The prenatal differentiation of CDS from other FOU is important because
      CDS is not amenable to in utero surgical intervention in the form of
      vesicoamniotic shunts. We evaluated the prenatal characteristics of 8 fetuses
      with CDS, including a pair of monozygotic twins concordant for CDS, in order to
      identify features that would enable differentiation from other forms of FOU.
      Pathologic examination in each of the 8 fetuses confirmed characteristic features
      of absent anal, genital, and urinary orifices associated with a smooth perineum
      and abnormal phallic development. Associated abnormalities included dysplastic
      kidneys in 6, hydroureters in 5, intraluminal colonic calcifications in 2, and
      hypoplastic lungs in 5. Five of these fetuses initially presented as posterior
      urethral valve syndrome. Six fetuses had megacystis, and 4 underwent
      vesicocenteses to evaluate urinary electrolytes, all of which were in the 'poor
      risk' category. Six fetuses were male and 2 female, contradicting earlier claims
      that CDS occurs only in females. Evaluation of candidates for in utero surgical
      intervention should include fetal karyotype, and CDS should be suspected in cases
      of FOU in whom the karyotype reveals a male fetus and sonographic evaluation
      demonstrates colonic calcifications or abnormal phallic development. Diagnostic
      microendoscopy may be of benefit in such cases.

PMID- 9650650
TI  - Management of a case of twin-to-twin transfusion syndrome by a combined surgical
      approach.
AB  - OBJECTIVE: The management of a case of severe twin-to-twin transfusion syndrome
      at 24 weeks of gestation is presented, using a combined surgical and medical
      approach. METHODS: Operative fetoscopy was used to coagulate placental vessels
      crossing the intertwin membranes. Repeated intrauterine transfusions were used to
      correct recurrent anemia in the donor twin. Selective three-dimensional placental
      angiography and directed histological analysis were used to study the placenta
      after delivery. RESULTS: Resolution of twin-to-twin transfusion syndrome was
      obtained by coagulation of placental anastomoses, but was followed by recurrent
      anemia in the donor twin. This was successfully treated by serial intrauterine
      blood transfusions, and 2 healthy twins were delivered at 31 weeks of gestation.
      One artery-to-vein anastomosis was demonstrated to be the only communication left
      between the two circulations. CONCLUSIONS: This case illustrates the limitations
      of placental surgery in twin-to-twin transfusion syndrome and highlights the need
      for ultrasound and Doppler follow-up of these high-risk fetuses to indicate
      further treatment. Placental anastomoses can be overlooked by macroscopic
      examination and injection technique, but can be demonstrated by placental
      angiography.

PMID- 9650651
TI  - Outcome of 116 moderate renal pelvis dilatations at prenatal ultrasonography.
AB  - To determine the incidence of urinary tract abnormalities detected in the
      presence of moderate fetal renal pelvis dilatation, we followed up pre- and
      postnatally 116 fetuses and children between 1985 and 1995. At prenatal
      ultrasound, 50 (43%) fetuses showed regressive dilatations, 57 (49%) a stable
      pattern, and 9 (8%) an evolutive pattern. In the presence of an evolutive
      dilatation, urinary tract obstruction was present in 8 cases. When a stable
      pattern was observed, i.e., a patent uropathy was present, surgical correction
      was performed in 27 of 53 (51%) cases. Regarding the postnatal evolution of 50
      prenatal regressive moderate dilatations, we observed in 12 of 50 (24%)
      vesicoureteric reflux, of which 5 (10%) required surgical correction, and it is
      concluded that careful and extensive follow-up is mandatory.

PMID- 9650652
TI  - Surgical approach of an early mammalian embryo: the rabbit model.
AB  - We describe an experimental surgical model in early rabbit embryo (12.5 days of
      gestation). Twenty-one embryos were operated, of which 9 survived the first
      postoperative week and 5 had normal further growth until term. As far as we can
      ascertain, this is the first successful report of a surgical approach in early
      mammalian embryos. We think that this model may be useful for workers involved in
      the study of early congenital malformations.

PMID- 9650653
TI  - Amniotic septostomy for the treatment of twin oligohydramnios-polyhydramnios
      sequence.
AB  - OBJECTIVE: To report our experience with intentional puncture of the intervening
      membrane ('septostomy') for the treatment of the twin oligohydramnios
      polyhydramnios sequence (TOPS). METHODS: 12 patients were diagnosed with TOPS
      based on ultrasonographic findings. A 20- to 22-gauge spinal needle was used to
      puncture the membrane between the twins without any attempt at amnioreduction in
      9 patients, while the procedure was combined with amnioreductions in 3 patients.
      RESULTS: Gestational age was 23.1 +/- 3.3 weeks at the time of septostomy and
      31.1 +/- 4.4 weeks at delivery. Rapid accumulation of fluid around the 'stuck'
      fetus occurred in all cases following a single procedure. Three of the 24 fetuses
      died in utero and 1 died on the fifth day of life, for a combined survival of
      83.3%. In the survivors, the septostomy to delivery interval ranged between 0.6
      and 13 weeks (mean +/- SD 8.3 +/- 4.8). CONCLUSION: Amniotic septostomy is a
      promising new method for the management of TOPS and is associated with survival
      rates that are better than, or comparable to, more invasive modalities. A
      multicenter trial comparing septostomy to other modalities is warranted.

PMID- 9650654
TI  - A simple method to estimate volume for fetal intravascular transfusions.
AB  - We derived a constant termed the transfusion coefficient to simplify the
      estimation of the fetal intravascular transfusion volume. The product of the
      estimated fetal weight (g) and 0.02 (transfusion coefficient), estimates the
      transfusion volume (ml) required to increase the fetal hematocrit by
      approximately 10 percentage points. Our estimation was comparable to Mandelbrot's
      technique and better than Plecas' method for estimating fetal transfusion
      volumes. Utilizing the transfusion coefficient to estimate the intravascular
      transfusion volume for an anemic fetus is simple, rapid and accurate.

PMID- 9650655
TI  - Fatal sepsis due to Escherichia coli after second-trimester amniocentesis.
AB  - The case of a pregnant woman (16th week) needing an amniocentesis is reported.
      She rapidly developed a septic shock. Despite vaginal delivery, curettage and
      antibiotherapy, the patient deteriorated with the onset of an acute respiratory
      distress syndrome and a typical disseminated intravascular coagulation.
      Bacteriological data showed positive blood cultures to Escherichia coli. Amniotic
      liquid was positive to the same E. coli. Cultures obtained from instruments,
      disinfectant solutions and gel used during the procedure were negative. On the
      contrary, amniotic and fetal cultures were positive to E. coli and Clostridium
      perfringens. She died 2 days later. The incidence of septic shock following
      amniocentesis is very low but we report the first case of fatal sepsis and
      multiorgan failure, due to E. coli and C. perfringens. The mechanisms of
      infection are discussed: contamination from the instruments, systemic
      dissemination of bacteria coming from an asymptomatic intra-amniotic infection,
      and inoculation of the placenta with a needle passing through the bowel.

PMID- 9650656
TI  - Effects of antenatal thyrotropin-releasing hormone on fetal heart rate and
      breathing movements.
AB  - OBJECTIVE: To determine the effect of maternally administered thyrotropin
      releasing hormone (TRH) on fetal heart rate (FHR) pattern and fetal breathing
      movements (FBM). METHODS: Prospective observational study of 75 pregnant women
      between 26 and 34 weeks' gestation in whom pharmacological fetal lung maturation
      was clinically indicated. Forty-minute recordings were made of FBM or FHR
      patterns before and after drug administration. Twenty-five received TRH 400
      microg as an intravenous bolus, 25 TRH 400 microg in 50 ml 0.9% saline as an
      intravenous infusion, and 25 acted as controls. Recordings were processed
      digitally to calculate the change in FHR (n = 45) and FBM parameters (n = 30).
      The main outcome measures for FHR were number of accelerations and decelerations,
      baseline rate, overall and short-term variation and duration of high and low
      variability, while for FBM they were rate, breath-to-breath interval and
      incidence. Results between groups were compared by analysis of variance. RESULTS:
      There was no significant change in FHR, accelerations or variation in any of the
      groups. Similarly, there was no change in the incidence of FBM. TRH administered
      as a bolus produced a small statistically but not clinically significant increase
      in breathing rate (mean delta = 35 breaths/h, p = 0.004), which was not seen in
      the TRH infusion and control groups. CONCLUSIONS: Maternally administered TRH as
      used to enhance fetal lung maturation has no clinically significant direct effect
      on FHR or FBM patterns.

PMID- 9650657
TI  - 'Dual positivity' for neural tube defects and down syndrome at maternal serum
      screening: gestational outcome.
AB  - OBJECTIVE: To evaluate the gestational outcome of pregnancies screen-positive for
      both neural tube defects (NTD) and Down syndrome (DS) ('dual positivity').
      METHODS: Among 10,667 mid-trimester women screened for DS and NTD with alpha
      fetoprotein (AFP), unconjugated estriol (uE3), and human chorionic gonadotropin
      (hCG), delivered up to July 1996, we have selected cases with both an unexplained
      AFP value > or = 2.5 multiples of median (MoM) and a DS risk > or = 1:250. All
      these pregnant women were managed with amniocentesis and/or CVS, ultrasound
      scans, and Doppler velocimetry. We have collected all data about the gestations
      with 'dual positivity' and no obvious explanation for these findings (cases with
      fetal malformations related to raised AFP). RESULTS: Twelve women (1.1:1,000)
      showed unexplained 'dual positivity'. Abnormal karyotypes were found in 3
      fetuses, and pregnancies were terminated: there were 2 triploidies with partial
      hydatiform mola, and 1 DS. In 9 cases the fetal karyotype was normal, but a
      confined placental trisomy 16 was found in 4. Of the 9 continuing gestations, 8
      displayed fetal growth retardation (FGR). One gestation ended with fetal death at
      27 weeks. All 9 fetuses were morphologically normal, and 8 were small for
      gestational age. CONCLUSIONS: 'Dual positivity' at NTD/DS screening may
      anticipate pregnancy complications. The finding of trisomy 16 confined to the
      placenta and FGR in 4 cases suggests that at least some fetuses with growth
      restriction may suffer from a distinct placental disease. Maternal serum
      screening may have implications different from DS and NTD, as demonstrated by the
      2 cases with triploidy and incomplete hydatiform mola, the 4 cases with placental
      trisomy 16, and the 4 cases of FGR of the 5 fetuses without chromosome
      abnormalities. As the pathologic outcome of these pregnancies is more important
      than the mere serum screening results, we feel that these cases need a strict
      work-up, including CVS, amniocentesis and ultrasound studies to better address
      the obstetrical management.

PMID- 9650658
TI  - Early antenatal diagnosis of cardiac defects using transvaginal Doppler
      ultrasound: new perspectives?
AB  - OBJECTIVE: Cardiac defects are the most prevalent congenital anomalies. Screening
      policies have adopted an 18- to 22-week ultrasound scan to detect such anomalies.
      However, diagnosis may be feasible early in pregnancy using transvaginal Doppler
      ultrasound. METHODS: Transvaginal ultrasound, including nuchal translucency (NT)
      measurement, is routinely performed at 10-13 weeks of gestation at our
      department. Complementary arterial and venous blood flow Doppler evaluation is
      also performed in cases of increased NT as a part of an ongoing research project.
      RESULTS: Ultrasound revealed complete atrioventricular septal defects in 2
      trisomic fetuses (trisomy 18 and 21) at 12 and 13 weeks of gestation,
      respectively, with increased NT and abnormal venous blood flow velocity.
      CONCLUSIONS: Increased NT has been associated with major chromosomal anomalies
      and is being increasingly related to cardiac defects. Considering that venous
      blood flow patterns may provide additional clues to the cardiac function, it may
      be useful as a complementary tool for the earlier diagnosis of structural cardiac
      anomalies.

PMID- 9650659
TI  - Blood gas and pH in the human fetus with severe anemia.
AB  - Leiden University Hospital is the national referral center for the management of
      fetal isoimmunization in The Netherlands. In this observational study, blood gas
      and acid-base measurements from 286 pretransfusion samples and 214 paired
      posttransfusion samples of 113 fetuses were analyzed. In umbilical arterial
      blood, we found a significant positive correlation between the degree of anemia
      and pH, as well as a significant negative correlation between degree of anemia
      and pO2. However, umbilical venous blood gas and pH remained virtually unchanged
      even in severe anemia. During intrauterine transfusion with unbuffered adult red
      cells, there was a small but statistically significant decrease of pH and pO2 in
      fetal blood. We conclude that severe fetal anemia is associated with decreased
      umbilical arterial pH, but that umbilical venous pH remains normal until shortly
      before death.

PMID- 9650660
TI  - Pastoral care utilization among women electing pregnancy termination for fetal
      anomalies.
AB  - OBJECTIVE: To identify determinants of requesting pastoral care (PC) at the time
      of pregnancy termination for fetal anomalies. METHODS: PC was provided by a
      hospital-based chaplain. Data were reviewed for 88 women who elected pregnancy
      termination. Nominal logistic regression and Kruskal-Wallis and Student t tests
      were used as appropriate. RESULTS: None of 37 women who underwent dilatation and
      curettage (D&C) or dilatation and evacuation (D&E) requested PC as compared with
      40 of 51 patients who underwent prostaglandin induction of labor (p < 0.001). The
      decision to seek PC was related to gestational age (p < 0.001), but not to
      maternal age, prior termination of pregnancy, gravidity, parity, racial
      background, or insurance status. The gestational age was also a significant
      predictor of the procedure performed (p < 0.001). D&C/D&E were significantly more
      likely to be performed at earlier gestational ages. Women seeking PC were less
      likely to have experienced previous pregnancy loss or the death of a child. Among
      women who sought PC, 20% had experienced previous pregnancy loss or the death of
      a child, as opposed to 54% of women in the prostaglandin group who did not seek
      PC (p = 0.03). In the D&C/D&E group, the figure was 46%. CONCLUSIONS: Utilization
      of PC is much more frequent among women undergoing prostaglandin induction of
      labor than D&C/D&E. Determinants of seeking PC are related to issues congruent
      with choices of the termination procedure. Patients who experienced a previous
      pregnancy loss or the death of a child are also less likely to feel the need, or
      do not want, chaplaincy involvement.

PMID- 9650662
TI  - Design and development strategy for the rotary blood pump.
AB  - Development of an antitraumatic antithrombogenic and durable blood pump is a very
      difficult task. Based upon this author's experience of over 35 years in the
      development of various types of cardiac prostheses, development strategies for a
      rotary blood pump are described. A step-by-step development strategy is thus
      proposed. Initially, the development of a 2 day antitraumatic pump (Phase 1)
      would be made. Then, conversion of this pump to a 2 week antithrombogenic pump
      (Phase 2) should be attempted. After the successful development of the Phase 2
      pump, the conversion of this device to a durable, implantable, and long-term
      blood pump (Phase 3) should be established. Based upon this development strategy,
      2 rotary blood pumps, namely, the axial flow blood pump and the centrifugal blood
      pump, have been developed in less than 6 years with modest development costs.

PMID- 9650661
TI  - Coenzyme Q10 fetal plasma levels.
AB  - OBJECTIVE: This study aims at determining a cutoff value differentiating the
      fetal from the adult coenzyme Q10 (CoQ10) values and comparing substantial
      increases in CoQ10 plasma levels in fetuses with hypoxic hypoxia and nonimmune
      fetal hydrops. METHODS: We have selected 61 pregnancies and determined the CoQ10
      levels in fetal and maternal samples obtained by cordocentesis. Our study
      included a control group and pregnancies with intrauterine growth retardation, Rh
      isoimmunization, nonimmune fetal hydrops, and fetal malformations. RESULTS: To
      differentiate the fetal from the adult values we have set 0.3 mg/ml as the cutoff
      value. The CoQ10 were higher only in fetuses with hypoxic hypoxia and nonimmune
      hydrops. CONCLUSION: Normal fetal CoQ10 plasma levels are lower than 0.3 mg/ml.

PMID- 9650663
TI  - Cleveland Clinic continuous flow blood pump: progress in development.
AB  - The Cleveland Clinic continuous flow blood pump is the central element of our
      innovative ventricular assist system (IVAS). Recent progress has been made in the
      design/fabrication of a pulsatile mock loop, journal bearing materials testing,
      and evaluation of a system control algorithm. These results have allowed an
      acceleration of our program.

PMID- 9650664
TI  - Eccentric roller type total artificial heart designed for implantation.
AB  - In the process of developing a completely implantable total artificial heart
      system, we have made an eccentric roller type total artificial heart and
      evaluated it by means of a mock circulatory system and by an acute animal
      experiment. The actuator of the artificial heart consists of 2 cylindrical drum
      type rollers which squeeze 2 blood chambers. The blood chambers are made of
      silicone rubber and are torus in shape. There is no valve used in this artificial
      heart. The artificial heart appears to be a nearly circular cylinder,
      approximately 10 cm in length and 8 cm in diameter. In the Donovan mock test, the
      artificial heart worked at a roller speed of 100-125 rpm with flow rates of 2.5
      3.0 L/min for the right side and 3.2-3.8 L/min for the left side, respectively.
      The electric power consumption was 19.0-24.7 W. Our artificial heart is
      characterized by an ejection of blood alternatively in the pulsatile mode without
      need for reversing the motor. In the ex vivo evaluation, circulation of an adult
      sheep was maintained with this artificial heart for 4 h.

PMID- 9650665
TI  - Implantable micropump system for augmented liver perfusion.
AB  - Liver cirrhosis, a worldwide health problem, decreases the blood flow through the
      liver. This in turn leads to dangerous portal hypertension and decreased
      metabolic function within the liver. To improve this situation, a new concept is
      proposed which involves introducing a microaxial blood pump into the portal vein.
      This device is intended to increase blood flow through the liver and to enhance
      hepatic function. Furthermore, high pressures will be reduced to physiological
      levels. The microaxial pump with its single stage impeller is powered by a
      proximally integrated microelectric motor. The pump unit is completely immersed
      within the blood vessel. Heat caused by electrical and mechanical losses will be
      transported into the blood. In vitro optimization of the pump design was
      accomplished using both hydraulic and hemolysis tests.

PMID- 9650666
TI  - Development of the small caliber centrifugal blood pump.
AB  - Regarding the development of a centrifugal blood pump to be connected directly
      with small diameter tubings for pediatric use while minimizing hemolysis, we have
      studied the inlet port side configurations of a pump using both a hemolysis test
      and computational fluid dynamics (CFD) analysis. We have conducted a hemolysis
      test on 2 models. The tapered shape inlet has proven to be lower in the index of
      hemolysis (IH) than the straight shape. CFD analyses utilizing expanded flow
      paths indicated that the flow velocity decreased as the fluid path became larger
      within the tapered nozzle. When entering the pump chamber, the flow rushed in at
      a greater velocity through the straight nozzle due to its small diameter. The
      straight shape showed an abrupt change in pressure around the entrance of the
      pump chamber while the tapered shape did not. The flow inlet angle of the
      straight model was observed to be larger than that of the tapered model because
      of its smaller turning radius.

PMID- 9650667
TI  - An implantable centrifugal blood pump with a recirculating purge system (Cool
      Seal system).
AB  - A compact centrifugal blood pump has been developed as an implantable left
      ventricular assist system. The impeller diameter is 40 mm, and pump dimensions
      are 55 x 64 mm. This first prototype, fabricated from titanium alloy, resulted in
      a pump weight of 400 g including a brushless DC motor. The weight of a second
      prototype pump was reduced to 280 g. The entire blood contacting surface is
      coated with diamond like carbon (DLC) to improve blood compatibility. Flow rates
      of over 7 L/min against 100 mm Hg pressure at 2,500 rpm with 9 W total power
      consumption have been measured. A newly designed mechanical seal with a
      recirculating purge system (Cool-Seal) is used for the shaft seal. In this seal
      system, the seal temperature is kept under 40 degrees C to prevent heat
      denaturation of blood proteins. Purge fluid also cools the pump motor coil and
      journal bearing. Purge fluid is continuously purified and sterilized by an
      ultrafiltration unit which is incorporated in the paracorporeal drive console. In
      vitro experiments with bovine blood demonstrated an acceptably low hemolysis rate
      (normalized index of hemolysis = 0.005 +/- 0.002 g/100 L). In vivo experiments
      are currently ongoing using calves. Via left thoracotomy, left ventricular (LV)
      apex descending aorta bypass was performed utilizing an expanded
      polytetrafluoroethylene (ePTFE) vascular graft with the pump placed in the left
      thoracic cavity. In 2 in vivo experiments, the pump flow rate was maintained at 5
      9 L/min, and pump power consumption remained stable at 9-10 W. All plasma free Hb
      levels were measured at less than 15 mg/dl. The seal system has demonstrated good
      seal capability with negligible purge fluid consumption (<0.5 ml/day). In both
      calves, the pumps demonstrated trouble free continuous function over 6 month (200
      days and 222 days).

PMID- 9650668
TI  - Performance of a continuous flow ventricular assist device: magnetic bearing
      design, construction, and testing.
AB  - A new centrifugal continuous flow ventricular assist device, the CFVAD III, which
      is fully magnetic bearing suspended, has been developed. It has only one moving
      part (the impeller), has no contact (magnetic suspension), is compact, and has
      minimal heating. A centrifugal impeller of 2 inch outer diameter is driven by a
      permanent magnet brushless DC motor. This paper discusses the design,
      construction, testing, and performance of the magnetic bearings in the unit. The
      magnetic suspension consists of an inlet side magnetic bearing and an outlet side
      magnetic bearing, each divided into 8 pole segments to control axial and radial
      displacements as well as angular displacements. The magnetic actuators are
      composed of several different materials to minimize size and weight while having
      sufficient load capacity to support the forces on the impeller. Flux levels in
      the range of 0.1 T are employed in the magnetic bearings. Self sensing electronic
      circuits (without physical sensors) are employed to determine the impellar
      position and provide the feedback control signal needed for the magnetic bearing
      control loops. The sensors provide position sensitivity of approximately 0.025
      mm. A decentralized 5 axis controller has been developed using modal control
      techniques. Proportional integral derivative controls are used for each axis to
      levitate the magnetically supported impeller.

PMID- 9650669
TI  - Fine trabecularized carbon: ideal material and texture for percutaneous device
      system of permanent left ventricular assist device.
AB  - The development of a percutaneous artificial internal organ system requires a
      reliable biocompatible connection between the external environment and the inside
      of the human body. Such is necessary for the success of a permanent left
      ventricular assist device. However, the search for a satisfactory interface at
      the epidermal level has proven to be difficult. Carbon has been proposed for this
      application, but its texture does not typically promote ingrowth from surrounding
      tissue. We have therefore employed a new processing method to produce a fine
      trabecularized carbon implant. The method for preparing the implant involves
      infiltrating low temperature pyrolytic carbon into the surface of a carbon core
      which is wrapped with carbon fabric. This results in a tightly woven porous
      structure of carbon (carbon fiber diameter: 35-50 microm, maximal pore size >200
      microm) with gradually increasing porosity from 15-75%. We implanted test samples
      percutaneously in a calf for in vivo histological evaluation. Thirty days after
      implantation epidermal downgrowth was minimal. Microscopic analysis revealed that
      a thin fibrous capsule surrounded the implant, and mature connective tissue with
      accompanying blood vessels filled the pores of the fine trabecularized carbon
      layer. From these results we suggest that fine trabecularized carbon is ideally
      suited for a percutaneous device system in a permanent left ventricular assist
      device.

PMID- 9650670
TI  - Development of a flow estimation and control system of an implantable centrifugal
      blood pump for circulatory assist.
AB  - A bypass flow rate estimation and control system (BECS) for an implantable
      centrifugal blood pump (ICBP) has been developed in our institute. The estimated
      flow rate (EF) of the ICBP was derived from the electric power consumption, the
      rotating speed of a motor, and the blood viscosity presumed by the hematocrit and
      body temperature. The error in the EF was 0.5 +/- 0.4 L/min in in vivo
      experiments for 40 days. The rotating speed of the motor was controlled
      automatically every 200 ms to bring the EF in accord with the desired flow rate
      (DF). The reactivity and accuracy of the BECS were investigated in in vitro and
      in vivo experiments. The ICBP was operated by the BECS in a mock circuit in
      parallel with a pulsatile ventricular assist device (PVAD) to simulate left heart
      bypass. The reactivity was evaluated by changing the DF from 7 L/min to 5 L/min
      at an afterload of 160/97 mm Hg. To evaluate the accuracy of the BECS, the ICBP
      was driven under the aortic pressure of 110/85 mm Hg in the abdominal wall of an
      adult goat (70 kg). The DF was set at 5 L/min for 4 min for the goat in an awake
      condition. It took 13 s to change the flow rate in the in vitro experiment. The
      measured flow rate (MF) was maintained at 5.0 +/- 0.2 L/min by the BECS in vivo.
      In conclusion, the BECS has moderate reactivity and accuracy.

PMID- 9650671
TI  - Intrathoracic and intraabdominal wall implantation of a centrifugal blood pump
      for circulatory assist.
AB  - An implantable centrifugal pump (ICP) 320 ml in volume and 830 g in weight has
      been developed for prolonged circulatory assist. The antithrombogenicity of the
      ICP is provided by a balancing hole in the center of the impeller. The
      watertightness and histocompatibility of the ICP are supported by its silicone
      ring seal and its casing of titanium and acrylic resin, respectively. The total
      efficiency of the ICP was 30% at a 5 L/min flow rate and a 100 mm Hg head. The
      heat generation, watertightness, and anatomical fitting of the ICP were assessed
      in an intrathoracic implantation in a goat (66 kg) and in an intraabdominal wall
      implantation in a goat (70 kg). Warfarin was given for anticoagulation in each
      experiment to keep the prothrombin time around 1.7 times that of the control. The
      temperatures of the pump surface, the pleura, and the room were measured every 3
      h. Anatomical fitting was evaluated by pathological observation after the
      termination of the experiment. The ICP could run for 40 days in the chest cavity
      and for 11 days in the abdominal wall. The temperature of the motor remained
      about 1.8 degrees C higher than the reference in both experiments. The ICP was
      completely covered by a layer of smooth fibrous tissue. The moisture content of
      the seals remained normal. Although a small amount of atelectasis was found in
      the lingula, neither lung adhesion nor necrotic change of the chest wall was
      observed. The inflammation of the surrounding tissue including foreign body
      reaction and thermal burn was minimal. In conclusion, the ICP has satisfied in
      vivo testing of its watertightness, exothermicity, and anatomical fitting.

PMID- 9650672
TI  - Clinical experiences of percutaneous cardiopulmonary support: its effectiveness
      and limit.
AB  - In recent years, several types of centrifugal pumps have been widely used as the
      main pumps for cardiopulmonary bypass (CPB) and postcardiotomy cardiac support.
      From April 1990 to March 1997, a percutaneous cardiopulmonary support (PCPS)
      system was used in 20 patients with an average age of 58 years (13 males and 7
      females). They comprised 11 ischemic, 6 valvular, 2 aortic, and 1 congenital
      heart disease patients. Our PCPS system consists of a centrifugal pump
      (BioMedicus BP-80), an oxygenator, and a reservoir. The entire blood contacting
      surface, including that of the thin wall cannulas, is coated by heparin bonded
      materials. As a result of this new technology, this system can be used for the
      long term without systemic heparinization. No major critical thrombi were
      revealed inside the pumps or circuits. Of the 20 patients, 7 (35%) (Group 1)
      could be weaned from PCPS, and the remaining 13 (Group 2) could not. In Group 1
      although 2 patients suffered from renal failure and pneumonia, respectively, both
      were discharged from our hospital. The long-term survival rate was 35%. In Group
      2 cerebral vascular damage was recognized in 3 patients, renal failure in 4,
      multiple system organ failure in 4, bleeding in 2, arrhythmia in 1, and leg
      ischemia in 2. Pulse pressure was significantly elevated due to the recovery of
      the native heart in Group 1, 2 days after support. However, in Group 2, it did
      not elevate, and the left ventricular ejection fraction was less than 30%,
      associated with high left atrial pressure. In conclusion, this heparin coated
      PCPS system was very simple and easy to control. It demonstrated long-term
      biocompatibility and was very effective in recovering deteriorated cardiac
      function. Quicker application of this system can play an important role in
      preventing severe complications and obtaining better clinical results. If long
      term support is necessary, a ventricular assist device (VAD), which is more
      powerful, durable, and biocompatible, has to be applied instead of PCPS.

PMID- 9650673
TI  - Left centrifugal pump cardiac assist with transseptal percutaneous left atrial
      cannula.
AB  - Left cardiac support postcardiotomy requires a second operation for removal of
      the atrial cannula following weaning from assistance. To avoid the risk of this
      procedure, we used a transseptal cannula prototype. The cannula was introduced
      percutaneously through the femoral vein and advanced into the left atrium guided
      by the finger of the surgeon. Optimal positioning of the tip of the cannula was
      verified by perioperative transesophageal echocardiography. A long arterial
      cannula was positioned in the descending aorta via the femoral artery and a
      Carmeda circuit with a centrifugal pump was connected to both cannulas. This
      procedure was used in 3 patients with low cardiac output who underwent emergency
      surgery, a 63-year-old patient referred for aortic and mitral valve replacement,
      a 54-year-old man for aortic valve replacement, and a 64-year-old patient in the
      acute phase of myocardial infarction after myocardial revascularization. The
      assistance was used systematically at the end of the operation. The assist flow
      was 1.2-2.6 L/min. The patients were all weaned from support between 18 h and 8
      days later. No complications related to the device occurred. Both cannulas were
      removed surgically from the femoral vessels without reopening the chest. This new
      procedure is of interest for 2 reasons: the systematic implantation allows for
      early assistance, and the use of a percutaneous approach avoids the risk of
      reopening the chest. More cases are needed to confirm this initial good
      impression.

PMID- 9650674
TI  - Safety of beating heart anastomosis during video-assisted coronary surgery
      attested by cardiac troponin I.
AB  - Our objective was to evaluate the safety of coronary anastomosis on the beating
      heart by measuring the release of cardiac troponin I during minimally invasive
      coronary artery bypass grafting (MICABG). Cardiac troponin I (cTnI) is a reliable
      marker of cardiac ischemia during heart operations under cardiopulmonary bypass
      (CPB). Ten patients (8 males and 2 females, aged 41-63) underwent MICABG with
      single vessel bypass grafting for left anterior descending coronary artery (LAD)
      stenosis (n = 7) or occlusion (n = 3). Video-assisted surgery with left anterior
      minithoracotomy was performed in all patients. Serial venous blood samples were
      collected for measurement of cTnI before LAD occlusion (T0), during anastomosis
      (T1) and 10 min (T2), 6 h (T3), 24 h (T4), 48 h (T5), and 72 h (T6) after
      coronary reperfusion. The assay method used a specific enzyme-linked
      immunosorbent Stratus autoanalyzer. Control coronary angiography was performed in
      all patients. There were no operative complications or reoperations for bleeding.
      The cTnI concentrations were expressed in ng/ml +/- SD. The mean cTnI level was
      less than 3.05 +/- 0.2 ng/ml (range 0-32.8). Values were T0 = 0, T1 = 0.4 +/-
      0.03, T2 = 1.15 +/- 0.2, T3 = 2.16 +/- 0.6, T4 = 1.5 +/- 0.3, T5 = 0.6 +/- 0.02,
      and T6 = 0.4 +/- 0.01. Angiography showed patent grafts in 9 patients. In one
      case, early internal thoracic artery (ITA) graft occlusion in a patient with 2
      vessel disease was correlated with a higher cTnI concentration (17.8 ng/ml).
      Percutaneous angioplasty was performed on the right coronary artery, complicated
      with dissection and cardiac failure. This patient died 3 months after the MICABG
      despite support from a ventricular assist device. In conclusion, collateral
      circulation developed in the setting of chronic coronary occlusion may be
      efficient for myocardial preservation during short periods such as coronary
      anastomosis. cTnI immunoassay confirmed the safety of coronary anastomosis on the
      beating heart during minimally invasive coronary operations.

PMID- 9650675
TI  - Summary of the 5th congress of the International Society for Rotary Blood Pumps,
      Marseille, France, 1997.

PMID- 9650676
TI  - Limitations and obstacles encountered in developing a practical hybrid hepatic
      assist device.

PMID- 9650677
TI  - The syndrome of acute near-total intrauterine asphyxia in the term infant.
AB  - Eleven term infants sustained an acute, near-total intrauterine asphyxia at the
      end of labor. Imaging studies documented a consistent pattern of injury in
      subcortical brain nuclei, including thalamus, basal ganglia, and brainstem; in
      contrast the cerebral cortex and white matter were completely or relatively
      spared. This pattern of injury correlated with the acute and long-term neurologic
      syndromes in these patients. Four patients had a severe neonatal encephalopathy
      that included prominent signs of brainstem dysfunction. The other seven patients
      had a moderate neonatal encephalopathy. Three of these patients had dystonia
      consistent with basal ganglia injury; all seven remained normocephalic and had
      good cognitive outcomes consistent with sparing of cerebral cortex and white
      matter. Finally, in all 11 patients, injury to organs other than the brain was
      usually subtle. The distribution of injury in these patients reflects the
      hierarchy of metabolic needs that are unmet after a severe, sudden disruption of
      substrate supply as occurs in an acute, severe asphyxia. Thus, the higher
      metabolic rate of the brain compared with other organs explains the significant
      neonatal encephalopathy with relative sparing of nonbrain organs. Similarly, the
      higher metabolic rate of subcortical nuclei compared with cerebral hemispheres
      explains the preponderance of subcortical damage. This clinical and imaging
      syndrome is in contrast with that seen in more prolonged but less severe
      intrauterine asphyxia, in which shunting of blood flow from nonbrain organs to
      the brain and from cerebral hemispheres to the thalamus and brainstem renders
      nonbrain organs and cerebral hemispheres most vulnerable.

PMID- 9650678
TI  - Visual function in children with merosin-deficient and merosin-positive
      congenital muscular dystrophy.
AB  - This study evaluates whether abnormalities of visual function are present in
      children with congenital muscular dystrophy and whether these, if present, are
      associated with merosin status or magnetic resonance imaging (MRI) findings.
      Twenty children (age range 5-17 years) with a diagnosis of classical congenital
      muscular dystrophy were assessed on visual acuity, stereopsis, and visual fields
      and the results compared with merosin status and MRI findings. Visual-evoked
      potential results were available for 14 of 20 children. All 20 children revealed
      normal results on all the clinical tests assessing visual function, irrespective
      of their merosin status or of MRI findings. Visual-evoked potentials were normal
      in the children with merosin-positive congenital muscular dystrophy but were
      abnormal in those with merosin deficiency. Unlike the other forms of congenital
      muscular dystrophy, which are associated with structural brain changes and eye
      involvement, visual function was always normal in the classical form of
      congenital muscular dystrophy. Interestingly, visual function was normal also in
      the group of children with merosin-deficient congenital muscular dystrophy who
      manifested white matter changes involving the occipital lobes on MRI and abnormal
      visual evoked potentials. Further studies are needed to specify the nature of the
      white matter changes observed with MRI and the reason for the dissociation
      between clinical and neurophysiologic findings.

PMID- 9650679
TI  - Antiepileptic drugs and atypical evolution of idiopathic partial epilepsy.
AB  - Six patients with classic benign epilepsy of childhood with centrotemporal
      spikes, treated with carbamazepine (four patients) or sodium valproate (two
      patients) evolved atypically because the epileptic disorder, diffusion of the
      electroencephalographic (EEG) discharges during wakefulness, and continuous spike
      and-wave during slow sleep associated with severe neuropsychologic abnormalities
      worsened. These features appeared after a seizure-free interval varying for 2
      weeks to 1 year 6 months after initiating therapy and remitted when the previous
      anticonvulsant drug was discontinued and either substituted with another drug or
      the patient was left without any treatment. Once the initial antiepileptic drug
      was discontinued and after a period roughly proportional to the duration of the
      clinical-EEG complication, the evolution of the patients' seizures was not
      unusual for this type of epilepsy, with patients eventually becoming free of both
      seizures and medication and reaching normal school achievement. The clinical
      complications cannot be attributed solely to the drugs. It must also be related
      to the underlying substract (i.e., the specific epileptic syndrome involved) that
      in some patients becomes susceptible to atypical evolution when either product is
      administered.

PMID- 9650680
TI  - Treatment of type I spinal muscular atrophy with noninvasive ventilation and
      gastrostomy feeding.
AB  - Type I spinal muscular atrophy (SMA) is a rapidly progressive, degenerative
      neuromuscular disease of infancy. In severe SMA, weakness, hypotonia, and bulbar
      involvement lead to progressive respiratory insufficiency and swallowing
      dysfunction, which are frequently complicated by aspirations. There are few
      studies reported in the literature that address the respiratory management of
      type I SMA. This article reports the results of treating four patients with
      infantile SMA with noninvasive positive pressure ventilation and gastrostomy
      feeding. All patients had gastroesophageal reflux disease, which was managed
      medically. Despite these therapies, survival was only 1 to 3.5 months after
      presenting with severe aspirations. The treatment strategy, which can be
      effective in less rapidly progressive neuromuscular diseases, did not alter the
      very poor prognosis of type I SMA. The treatment options are reviewed, and a
      strategy designed to optimize quality of life for infants with this fatal disease
      is presented.

PMID- 9650681
TI  - Dysarthria in children with cerebellar or brainstem tumors.
AB  - Speech features were perceptually analyzed in two groups of children. The first
      group (n = 6) had undergone cerebellar tumor resection, and the second group (n =
      6) included children with brainstem tumors. Children belonging to the first group
      became dysarthric after a postoperative mute phase. Slow speech rate was a
      specific feature, but scanning speech and irregular articulatory breakdown (i.e.,
      prominent characteristics in adult ataxic dysarthria) were not observed. In the
      second group, hypernasality was a prominent characteristic and resembled flaccid
      dysarthria in adults. These findings suggest that acquired childhood dysarthria
      needs a proper classification.

PMID- 9650682
TI  - Liposteroid (dexamethasone palmitate) therapy for West syndrome: a comparative
      study with ACTH therapy.
AB  - Dexamethasone palmitate (liposteroid) was used for the treatment of West syndrome
      and compared with adrenocorticotropic hormone (ACTH) therapy. A single
      intravenous injection of liposteroid (0.25 mg/kg) was administered seven times in
      3 months (total dosage = 1.75 mg/kg) to five symptomatic patients with West
      syndrome, aged 4-11 months. ACTH (0.025 mg/kg/day) was administered
      intramuscularly for 6 weeks according to the conventional therapy in Japan (total
      dosage = 0.625 mg/kg) to five symptomatic patients with West syndrome, aged 6-10
      months. Nodding spasm and hypsarrhythmia on EEG disappeared in all patients in
      the liposteroid therapy group within four doses; however, partial seizures and
      focal spikes on EEG reappeared in three patients 2 months after the end of
      liposteroid therapy. In the ACTH therapy group, nodding spasm and hypsarrhythmia
      on EEG similarly disappeared during treatment in all patients, but nodding spasm
      reappeared 2 months after therapy in two patients and partial seizures reappeared
      in one patient 3 months after therapy. No notable adverse reactions occurred in
      the liposteroid group, but transient dysfunction of the thyroid and anterior
      pituitary gland and increased levels of serum cortisol were experienced in the
      ACTH group. These results suggest that glucocorticoid incorporated in a lipid
      emulsion is useful for the treatment of West syndrome.

PMID- 9650684
TI  - Ultracytochemical analysis of E-PTA-positive synaptic junctions in postmortem
      examined brains with neurologic disorders.
AB  - The synaptic junctions from four postmortem-examined brains were studied
      ultracytochemically, using the ethanolic phosphotungustic acid (E-PTA) method. A
      noteworthy finding was the presence of variable-shaped vesicles that were not
      observed in the control E-PTA-treated preparations. This structural change in
      synaptic junctions is thought to represent a degenerative process. It is
      suggested that the neuronal transmission in brains with acquired neuropathologic
      abnormalities may be impaired because of the degenerative change in synaptic
      junctions.

PMID- 9650683
TI  - Neurophysiologic evaluation of long-term desferrioxamine therapy in beta
      thalassemia patients.
AB  - Forty patients with beta-thalassemia major (BTM), between 11 and 19 years of age
      and maintained on long-term desferrioxamine (DFO) treatment, were examined by
      evoked potential and nerve conduction velocity studies to investigate a possible
      involvement of the auditory, visual, somatosensory, or peripheral nervous
      pathways. Pathologic findings in brainstem auditory-, visual-, and somatosensory
      evoked potentials, and nerve conduction velocity studies were demonstrated in
      25%, 15%, 7.5%, and 25% of the patients, respectively, whereas 15% demonstrated
      involvement of multiple neural pathways. Subclinical involvement of the auditory
      pathway was statistically associated with higher mean daily DFO dose and longer
      duration of DFO therapy, whereas abnormalities regarding the somatosensory
      pathways were related to older age, longer mean duration of DFO therapy, and
      lower serum copper levels. Involvement of the peripheral nervous system was
      related to lower serum copper levels. Multiple involvement of neural pathways was
      related to longer mean duration of DFO therapy. We conclude that risk factors
      related to long-term DFO treatment are only partly responsible for the
      subclinical involvement of neural pathways demonstrated in beta-thalassemia major
      patients.

PMID- 9650685
TI  - mtDNA nt3243 mutation, external ophthalmoplegia, and hypogonadism in an
      adolescent girl.
AB  - A 14-year-old girl presented with a 3-month history of easy fatigue and exercise
      intolerance, especially when climbing stairs. She had a mild ptosis and mild
      limitation of upward gaze. Her puberty was delayed, and she manifested
      hypogonadotrophic hypogonadism. Serum lactic and pyruvic acids were elevated.
      Cranial magnetic resonance imaging was normal. Muscle biopsy documented typical
      ragged-red fibers. A point mutation at nucleotide 3243 in the tRNALeu(UUR)
      (typical mitochondrial encephalomyopathy, lactic acidosis, and stroke-like
      episodes (MELAS) mutation) was detected in mitochondrial DNA from both blood and
      muscle tissues, indicating that our patient was suffering from a mitochondrial
      myopathy. Hypogonadism may be a manifestation of the MELAS nucleotide 3243
      mutation.

PMID- 9650686
TI  - Dancing eye syndrome and hyperphosphatasemia.
AB  - An 11-month-old boy with a relapsing dancing eye syndrome associated with
      elevation of serum alkaline phosphatase, lactate dehydrogenase, and
      aminotransferase activities is reported. During two clinical episodes the serum
      alkaline phosphatase activity increased up to four times the upper reference
      limit, remained elevated for a few weeks and normalized gradually in parallel
      with clinical improvement under steroid therapy. We found no evidence of liver or
      bone pathology nor of a neural crest tumor. The association between dancing eye
      syndrome and hyperphosphatasemia has not yet been described. The beneficial
      effect of the steroid therapy strengthens the hypothesis of an autoimmune origin.

PMID- 9650687
TI  - Focal pachypolymicrogyria in three siblings.
AB  - The malformation of focal pachypolymicrogyria might be the manifestation of an X
      linked recessive disorder according to the results of this study. Three siblings
      revealed focal pachypolymicrogyria on magnetic resonance imaging (MRI) and had a
      strong family history of epilepsy and mental retardation. All three siblings had
      the same mother; the father of Patient 1 was not related to the mother, but the
      father of Patients 2 and 3 was related to her. The MRI of the father of Patients
      2 and 3 demonstrated focal pachypolymicrogyria. The mother's MRI was normal. In
      this family, epilepsy or mental retardation was found mainly in the males
      (Patient 3 was an exception), and they were all born to female members of this
      family, not male. Patient 3 was probably a homozygote with an X-linked recessive
      inheritance, and therefore, she demonstrated the most severe clinical findings.

PMID- 9650688
TI  - Pseudotumor cerebri in Lyme disease: a case report and literature review.
AB  - Pseudotumor cerebri is an unusual presentation of Lyme disease. The case of an 8
      year-old girl with pseudotumor cerebri secondary to acute neuroborreliosis is
      reported. She presented with acute onset of headache, papilledema, sixth nerve
      palsy, increased intracranial pressure, and cerebrospinal fluid pleocytosis.
      Serum and cerebrospinal fluid Lyme antibodies were positive. Twelve reported
      cases that mostly presented with systemic findings and signs of Lyme disease
      before development of pseudotumor cerebri were reviewed. We conclude that acute
      neuroborreliosis can present with pseudotumor cerebri as an initial
      manifestation. It is important to include Lyme disease in the differential
      diagnosis of pseudotumor cerebri in an area endemic for Lyme disease.

PMID- 9650689
TI  - Successful treatment of progressive myoclonus epilepsy with TRH.
AB  - Thyrotropin-releasing hormone (TRH) is sometimes used for the treatment of
      neurologic disorders such as intractable epilepsy and spinocerebellar
      degeneration. A 14-year-old girl with progressive myoclonus epilepsy was treated
      with intravenous TRH for 12 months. Clinical symptoms, such as cortical myoclonus
      and cerebellar signs, were improved, and P25-N33 amplitudes of somatosensory
      evoked potentials decreased after TRH therapy. P100 amplitudes on flash visual
      evoked potentials and photosensitivity on electroencephalograms also decreased
      but only temporarily. Changes in neurophysiologic findings after TRH therapy
      indicate that TRH inhibits hyperexcitability in the sensorimotor cortex and the
      visual cortex. Therefore, intravenous TRH therapy is recommended as an
      alternative therapy in the treatment of progressive myoclonus epilepsy.

PMID- 9650690
TI  - New syndrome with the Sakoda complex, bilateral anophthalmia, and cortical
      dysgenesis.
AB  - An 8-year-old Japanese boy had Sakoda complex (basal encephalomeningocele,
      agenesis of the corpus callosum, and cleft lip and/or palate) associated with
      bilateral anophthalmia, dysgenesis of the cerebral cortex, severe mental
      retardation, and intractable epilepsy as core symptoms and hemiparesis,
      microcephalus, short stature, and hemivertebra. Tada and Nakamura described the
      first case of the Sakoda complex associated with bilateral anophthalmia, cortical
      dysgenesis, neonatal-onset seizures, and severe mental retardation. Fourteen
      patients with the Sakoda complex with or without ocular dysplasia were reviewed.
      It is proposed that these cases belong to a clinical entity that is
      distinguishable from the remaining 12 patients because of bilateral anophthalmia,
      cortical dysgenesis, and its resulting severe mental retardation and intractable
      epilepsy. There is a possibility that these two cases are one severe end of
      certain spectrum disorders in which certain common gene(s) might be implicated.

PMID- 9650691
TI  - Hemimegalencephaly and Hirschsprung's disease: a unique association.
AB  - A 2-year-old boy with hemimegalencephaly and Hirschsprung's disease is reported.
      The unique association of these two entities is considered to be the presence of
      a common insult or insults that affect the innervation of the bowel and the
      formation of the cerebral cortex. Short-segment subtype of Hirschsprung's disease
      may suggest that this effect occurred between the eighth and twelfth weeks of
      gestation. Although there is a well-known coexistence of Hirschsprung's disease
      with the malformations that share a common neurocristopathic origin
      (abnormalities of neural crest cell growth, migration, or differentiation), a few
      extremely rare cases, as in this case, might reflect the coexistence of
      Hirschsprung's disease with a cerebral malformation (i.e., hemimegalencephaly)
      that is a nonneurocristopathic entity by itself.

PMID- 9650692
TI  - Parkinsonian syndrome complicating systemic lupus erythematosus.
AB  - Two girls with florid extrapyramidal parkinsonism complicating systemic lupus
      erythematosus (SLE) are reported. One patient (15 years old) presented with
      extreme rigidity, irritability, and mutism initially diagnosed as acute
      psychosis. Examination revealed severe extrapyramidal akinetic mutism, along with
      marked restlessness. CT and MRI imaging of the brain were unremarkable. EEG
      revealed moderate generalized disturbance of background activity. 99mTc-HmPAO
      SPECT cerebral scanning detected decreased regional cerebral blood flow at the
      basal ganglia. Dopamine-agonist drugs led to complete recovery after 3 months,
      along with normalization of EEG and SPECT alterations. The second patient (16
      years old) was assessed for progressive bradykinesia and apathy impeding her
      active daily activities, and she was suspected to have developed depression.
      Neurologic assessment revealed a parkinsonian syndrome that was less severe than
      that of the first patient. The EEG showed mild disturbance of background
      activity, and 99mTc-HmPAO SPECT demonstrated impaired regional cerebral blood
      flow over the basal ganglia. A parkinsonian extrapyramidal syndrome complicating
      SLE should therefore be taken into account in any patient with SLE presenting
      with marked behavioral alterations, rigidity, or akinetic mutism.

PMID- 9650693
TI  - LE or not LE--that is the question: an unsuccessful attempt to separate
      lymphocytic infiltration from the spectrum of discoid lupus erythematosus.
AB  - Lymphocytic infiltration of the skin (LIS) has been claimed to be a distinct
      entity that differs from discoid lupus erythematosus (DLE) by the lack of
      epidermal changes, negative immunofluorescence tests, and differences in the
      composition of the inflammatory cell infiltrate. In studies that sought to
      distinguish both conditions, however, cases of established lupus erythematosus
      without epidermal involvement have not been considered. We studied 72 patients
      with the clinical and histopathologic diagnosis of either LIS or DLE in regard to
      the same clinical, histopathologic, immunofluorescence, and immunohistochemical
      criteria. No significant differences were noted between cases with and without
      epidermal involvement on the one hand and between cases with and without
      immunofluorescence or clinical findings suggestive of lupus erythematosus on the
      other. Based on our findings, it is not possible to separate LIS from the
      spectrum of DLE.

PMID- 9650694
TI  - Apoptosis in the pathogenesis of cutaneous lupus erythematosus.
AB  - Defective regulation of apoptosis may play a role in the development of
      autoimmune diseases such as systemic lupus erythematosus, in which the skin is a
      prominent target. To our knowledge, however, the nature of epidermal changes in
      cutaneous lupus erythematosus (LE) has not previously been investigated. We
      investigated the involvement of apoptosis in cutaneous LE. A total of 44 lesional
      skin samples from patients with cutaneous LE, 44 skin samples from patients with
      scleroderma, five skin specimens from patients suffering from dermatomyositis,
      and 13 normal skin samples were stained immunohistochemically with monoclonal
      antibodies to Ki-67, p53 (DO-7), and bcl-2. The lesional skin from cutaneous LE,
      except LE profundus, showed a marked increase in Ki-67- and p53-positive
      keratinocytes, which were predominantly located in the basal layer of the
      epidermis and follicle, and a drastic reduction in the number of bcl-2-positive
      cells localized in the basal cell compartment. With TdT-mediated dUTP-biotin nick
      end-labeling staining, we demonstrated that extensive apoptosis occurred in
      almost the whole epidermis of cutaneous LE, except in cases of LE profundus. This
      abnormal expression of Ki-67, p53, and bcl-2 and the occurrence of apoptosis in
      the epidermis was also observed in epidermis from patients with dermatomyositis,
      but not in that from patients with scleroderma.

PMID- 9650695
TI  - Histopathologic differentiation between localized and systemic scleroderma.
AB  - It is widely accepted that a histopathologic differentiation between localized
      scleroderma (LS) and systemic scleroderma (SS) is not always possible. With the
      objective of identifying differentiating histopathological features between them,
      32 cases of LS and 19 cases of SS were reviewed. Histological features such as
      the distribution, composition, and density of the inflammatory cell infiltrate,
      thickness of the dermis, alterations of dermal collagen, and the presence of
      calcification were evaluated in each case. On the basis of our observations, LS
      and SS can be differentiated usually by the distribution and density of the
      inflammatory infiltrate and by the involvement of the papillary dermis.
      Inflammatory changes are more prominent in LS than in SS. Sclerosis of the
      papillary dermis is frequently seen in LS but is absent in SS.

PMID- 9650696
TI  - The asteroid bodies of sporotrichosis.
AB  - Some believe that asteroid bodies (AB) in sporotrichosis are nonspecific and are
      equivalent to the AB of sarcoidosis and other granulomatous diseases. We studied
      25 skin biopsy specimens of sporotrichosis in which AB were demonstrated, ten of
      them with Sporothrix-positive culture. Immunohistochemistry was performed in
      paraffin-embedded biopsy specimens using an anti-Sporothrix antibody. The same
      procedures were done with seven biopsy specimens of lobomycosis, which contained
      AB within giant cells. These did not react with the anti-Sporothrix antibody, and
      by electron microscopy they displayed filamentous and myelin figures similar to
      the AB of sarcoidosis. In sporotrichosis, the AB are extracellular eosinophilic
      structures, 15-35 microm in diameter, and located within abscesses. One to three
      are found in a section. They consist of a central yeast, surrounded by
      eosinophilic spicules. The yeast stains with the anti-Sporothrix antibody, while
      the spicules do not. Therefore, AB in sporotrichosis are specific for disease.
      Visualization of the spicules alone can lead to the demonstration of the AB in
      adjacent sections, and thus is a useful clue in the diagnosis of sporotrichosis.
      Sporotrichotic AB must not be confused with the intracellular AB seen in giant
      cells of granulomatous reactions, which are filamentous and myelin figures that
      contain lipid.

PMID- 9650697
TI  - Detection of Epstein-Barr virus and HTLV-I in T-cell lymphomas of skin in Taiwan.
AB  - Viral etiology has been associated with the pathogenesis of T-cell lymphomas of
      skin (TCLS). Therefore, we studied the presence of Epstein-Barr virus (EBV) and
      type I human T-cell lymphotropic virus (HTLV-I) in tumor cells of TCLS to
      determine the significance of these viruses with the disease. A retrospective
      study was conducted on the skin tissues from 28 Chinese patients with TCLS. We
      used in situ hybridization, immunohistochemistry, and polymerase chain reaction
      to determine the presence of viruses. Among the 28 cases, HTLV-I was only
      detected in two cases with adult T-cell leukemia/lymphoma, not in other cases of
      TCLS. This suggests that HTLV-I may not play a significant role in the
      oncogenesis of TCLS in Chinese patients. Conversely, EBV was detected in 12 cases
      (42.9%), including the secondary TCLS, large cell lymphoma, mycosis fungoides,
      adult T-cell leukemia/lymphoma, and angiocentric lymphoma. Nevertheless, latent
      membrane protein 1 was not detected in any of the EBV-positive cases. Neither was
      any correlation found between the presence of EBV in TCLS and the prognosis or
      the severity of the skin lesion. Although there is a close association of EBV
      with a portion of TCLS, its pathogenic role needs further investigation.

PMID- 9650698
TI  - p16 and p21WAF1 protein expression in melanocytic tumors by immunohistochemistry.
AB  - To determine whether variation in the level of expression of p16 and p21WAF1
      (p21) is associated with critical stages in cutaneous melanoma development or
      progression, the expression of these antigens was analyzed by
      immunohistochemistry in 110 benign and malignant melanocytic lesions.
      Differential expression of p16 protein has been reported in cutaneous melanocytic
      lesions, with loss of expression associated with the invasive stage of tumor
      development. Expression of p16 was seen in 31 of 35 benign melanocytic tumors
      (89%), 11 of 12 in situ melanomas (92%), 19 of 38 invasive primary melanomas
      (50%), and 16 of 25 metastatic melanomas (64%). There was a significant
      difference in the expression level of p16 observed in in situ versus invasive
      primary melanomas (p = 0.006), which is consistent with loss of normal p16
      activity occurring in association with malignant tumor invasion. Overall, p21
      levels were found to be low or undetectable in the majority of benign lesions,
      with greater p21 expression seen in malignant tumors. p21 was expressed in 28% of
      nevi, 60% of in situ melanomas, 61% of invasive melanomas, and 48% of metastatic
      melanomas. Among primary invasive tumors, the frequency of p21 expression
      increased with level of invasion (p < 0.01) and with increasing thickness (p <
      0.01). However, differences in p21 expression were not clearly related to a
      particular stage of melanoma development.

PMID- 9650699
TI  - C-fos protein expression in Spitz nevi, common melanocytic nevi, and malignant
      melanomas.
AB  - The expression of c-fos protein was studied in formalin-fixed, paraffin-embedded
      sections of 11 compound Spitz nevi (SNs), 16 ordinary compound melanocytic nevi
      (MNs), and 17 malignant melanomas (MMs) using monoclonal antibody MAB1283 and an
      immunoperoxidase technique. Eleven (100%) SNs, 15 (94%) MNs, and 16 (94%) MMs
      showed positive reactions in some of the tumor cells (p = nonsignificant). In the
      majority of the tumors the staining was located in nuclei and graded as moderate
      to strong in intensity. The percentages of positively stained cells did not
      differentiate the three types of tumor, although they were higher in the
      melanocytic nevi. Most of the lesions with a significant dermal component did not
      show stratification of staining with progressive descent into the dermis.
      Positive staining for c-fos was also frequently found in the normal skin
      constituents within and adjacent to the melanocytic tumors. In conclusion, the
      pattern of expression of c-fos in routinely processed specimens does not
      differentiate between SNs, MNs, and MMs.

PMID- 9650700
TI  - A case of glomeruloid hemangioma associated with multicentric Castleman's
      disease.
AB  - Glomeruloid hemangioma is a term that was coined J.K.C. Chan and colleagues in
      1990 because the condition is histopathologically similar to renal glomeruli. In
      the three cases described to date, there have been signs of POEMS syndrome of
      multicentric Castleman's disease. We present the case of a 44-year-old Korean
      woman who developed glomeruloid hemangioma in association with multicentric
      Castleman's disease and some features of POEMS syndrome. It is interesting that
      in this patient, the first biopsy specimen revealed an immature vascular tumor
      that could not be precisely classified and the second indicated glomeruloid
      hemangioma. The present case may lend support to the suggestion that in POEMS
      disease, some types of vascular proliferations develop in response to angiogenic
      stimuli that show a spectrum of histopathologic features, and glomeruloid
      hemangioma is one of the reactive vascular proliferations. We believe that the
      primitive vascular tumor seen in the first biopsy specimen may be the most
      immature stage of this spectrum.

PMID- 9650701
TI  - Mycosis fungoides palmaris et plantaris or acral pagetoid reticulosis?
AB  - There has been ongoing debate about the nature of Woringer-Kolopp disease
      (unilesional pagetoid reticulosis). Despite the histologic resemblance to mycosis
      fungoides, these lesions are typically solitary and indolent. Recently, cutaneous
      plaques of epidermotropic lymphocytes restricted to acral sites resembling
      Woringer-Kolopp disease were reported to show T-cell clonality, leading to the
      designation mycosis fungoides palmaris et plantaris. We describe a similar case
      of recurrent plaques on palms and soles of a 45-year-old man that persisted for
      >14 years without other cutaneous or systemic disease. Histologically, the
      lesions were comprised of epidermotropic atypical lymphocytes with sparse dermal
      infiltrates. Immunohistochemically, the majority of intraepidermal lymphocytes
      labeled as CD8-positive suppressor/cytotoxic T cells and expressed alphaE beta7
      (CD103), an integrin associated with epitheliotropism. Polymerase chain reaction
      studies revealed similar clonal gene rearrangements of T-cell receptors beta and
      gamma in tissue from both palm and sole. In view of these findings, the diagnosis
      of mycosis fungoides palmaris et plantaris may be appropriate. To date, however,
      the lesions have remained localized and continue to resolve spontaneously. As
      such, the behavior is similar to what has been described as pagetoid reticulosis.
      Long-term follow-up will be necessary to determine the biologic potential of this
      disease.

PMID- 9650702
TI  - Membranocystic lesions in a patient with cytophagic histiocytic panniculitis
      associated with subcutaneous T-cell lymphoma.
AB  - A 51-year-old Japanese woman had erythematous, tender subcutaneous nodules on her
      lower legs and buttocks, as well as fever, pancytopenia, and liver dysfunction.
      Histopathologic examination of the nodules showed subcutaneous T-cell lymphoma
      with cytophagocytosis and membranocystic lesions. Our patient was unique in
      having the combination of cytophagic histiocytic panniculitis due to subcutaneous
      T-cell lymphoma and membranocystic lesions.

PMID- 9650703
TI  - Primary cutaneous Langerhans cell histiocytosis in an adult.
AB  - A 76-year-old man with Langerhans cell histiocytosis was admitted with an
      asymptomatic, dark red nodule on his left buttock. Histologic examination of the
      nodule showed a dense dermal infiltrate of histiocytic cells with bean-shaped
      nuclei; these cells reacted with antibodies to S-100 and CD1a. Ultrastructural
      analysis showed Birbeck granules in the cytoplasm of the histiocytic cells.
      Inguinal lymph node involvement subsequently developed in the patient and
      cutaneous nodules recurred three times in the inguinal area. Four years have
      passed since he first was admitted to our hospital with the cutaneous nodule on
      his buttock, and he is doing well without any intensive treatment except wide
      excision of the nodules and inguinal lymph nodes. We believe this case should be
      classified as one of "benign" primary cutaneous Langerhans cell histiocytosis
      based on the clinical course.

PMID- 9650704
TI  - Synovial metaplasia in lipoma.
AB  - We present a unique case of a lipoma with widespread synovial metaplasia. A 52
      year-old woman had a recurrence 1 year after excision of a subcutaneous lipoma of
      the neck. Histologically, the primary tumor was an ordinary lipoma. The recurrent
      tumor was a myxoid lipoma with synovial metaplasia. The synovial metaplastic
      process manifested as labyrinthlike clefts, which were lined by one or more
      synovial-like cell layers. Ultrastructurally, the synovial metaplastic cell had
      secretory, phagocytic, and fibroblastlike features.

PMID- 9650705
TI  - Myxoid malignant fibrous histiocytoma mimicking papular mucinosis.
AB  - Malignant fibrous histiocytoma is the most common type of soft tissue sarcoma in
      late adulthood. The myxoid variant of malignant fibrous histiocytoma, also known
      as myxofibrosarcoma, can develop in subcutaneous rather than deep soft tissue,
      and the true extent of these superficial tumors is often underestimated. Patients
      with these low-grade myxoid malignant fibrous histiocytomas have an excellent 5
      year survival rate, and it is therefore important to recognize them. We present a
      case with a superficial cutaneous accumulation of mucin that was diagnosed
      clinically and histologically as papular mucinosis. In retrospect, a subcutaneous
      presentation of myxofibrosarcoma should have been considered.

PMID- 9650706
TI  - Syringomatous changes of eccrine sweat ducts associated with prurigo nodularis.
AB  - Alteration of the eccrine sweat ducts has been observed in association with an
      expanding list of conditions. To our knowledge, this phenomenon has not been
      described in association with prurigo nodularis. We report on a 68-year-old man
      with a fibrotic nodule on his chin that had been present for 8 months.
      Microscopic examination showed marked hyperkeratosis overlying the epithelium.
      There was also hypergranulosis, marked acanthosis, and irregular elongation of
      the rete ridges. These findings were consistent with prurigo nodularis. In
      addition, within the reticular dermis, there was marked fibrosis and a
      proliferation of eccrine sweat ducts. The ducts were enlarged and varied from
      cystic to rarely solid structures. Rare ducts formed a tadpole-shaped tail,
      reminiscent of syringoma. The duct lining demonstrated a multilayered epithelium
      that was three to eight cells thick, yielding a solid component to some of the
      cysts. Although some of these features were similar to those of a syringoma, the
      typical small gland proliferation and bilayered lining was not evident. This case
      (a) demonstrates the association of syringomatous changes of eccrine sweat ducts
      with yet another condition, prurigo nodularis, and (b) emphasizes the importance
      of differentiating this benign reactive process from the malignant neoplasms
      microcystic adnexal carcinoma and squamous cell carcinoma.

PMID- 9650707
TI  - A review of tumor suppressor genes in cutaneous neoplasms with emphasis on cell
      cycle regulators.
AB  - Cells normally have five options. These include renewal or proliferation,
      terminal differentiation, quiescence, senescence, and apoptosis. Many factors
      interact with cell cycle regulators to direct the cells toward these different
      options. Tumor suppressor genes play a pivotal role in this process. Alterations
      in these genes may limit the options that cells have and thus play a significant
      role in the multistep process of carcinogenesis. We will focus on tumor
      suppressor genes and especially tumor suppressor genes that interact directly
      with the cell cycle proteins.

PMID- 9650708
TI  - Patterns versus mechanisms of cutaneous metastases.

PMID- 9650709
TI  - Spiradenocylindroma--more than a coincidence?

PMID- 9650710
TI  - Interactive CD34-positive fibroblasts and factor XIIIa-positive histiocytes in
      cutaneous mesenchymal tumors.

PMID- 9650711
TI  - p53 protein and Kaposi's sarcoma.

PMID- 9650712
TI  - Cutaneous apocrine mixed tumor: derived from the apocrine duct of the folliculo
      sebaceous-apocrine unit?
AB  - We report a case of cutaneous mixed tumor (CMT) composed of tubular branching
      structures lined by cells with apocrine characteristics. In addition, an apocrine
      duct in the outer sheath of an hair follicle was connected to the mixed tumor, a
      previously unreported finding. Follicular and sebaceous differentiation have been
      described in CMT, leading some observers to suggest the existence of an apocrine
      type of CMT and its presumed differentiation toward the folliculo-sebaceous
      apocrine unit (FSAU). Our case demonstrated continuity of an apocrine duct in the
      FSAU and lends support to the previous speculations about the histogenesis of
      apocrine type of CMT.

PMID- 9650713
TI  - Isolation and characterization of insulin in Russian sturgeon (Acipenser
      guldenstaedti).
AB  - Insulin was isolated from the pancreas of Chondrostean fish, the Russian
      sturgeon, Acipenser guldenstaedti, by acid-ethanol extraction followed by ion
      exchange and reverse-phase high-performance liquid chromatographies. The amino
      acid sequence determined by automated Edman degradation is as follows: A-chain
      (21-amino-acid peptide), H-Gly-Ile-Val-Glu-Gln-Cys-Cys-His-Ser-Pro-Cys-Ser-Leu
      Tyr-Asp-Leu-Glu-As n-Tyr-Cys-Asn-OH; and B-chain (31-amino-acid peptide), H-Ala
      Ala-Asn-Gln-His-Leu-Cys-Gly-Ser-His-Leu-Val-Glu-Ala-Leu-Tyr-Leu-Va l-Cys-Gly-Glu
      Arg-Gly-Phe-Phe-Tyr-Thr-Pro-Asn-Lys-Val-OH. The sturgeon insulin appears to be
      identical with one of two forms of paddlefish insulin and differs from the other
      form by a single substitution in the A-chain, Asp15: His15. The amino acid
      sequence of sturgeon insulin is more similar to the amino acid sequence of
      mammalian insulins than of other fish insulins. Sturgeon insulin showed parallel
      but weaker displacement than porcine insulin and pink salmon insulin in their
      respective radioimmunoassays and was less potent than porcine insulin in
      displacing radiolabeled porcine insulin bound to partially purified rat liver
      plasma membranes.

PMID- 9650714
TI  - Comparison of the binding of alpha-helical and beta-sheet peptides to a
      hydrophobic surface.
AB  - The induction and stabilisation of secondary structure for a series of
      amphipathic alpha-helical and beta-sheet peptides upon their binding to lipid
      like surfaces has been characterised by reversed phase high-performance liquid
      chromatography (RP-HPLC). In addition, a series of peptides which have been shown
      to switch from beta-sheet to alpha-helical conformation upon transfer from a
      polar to a non-polar solution environment also have been studied. Binding
      parameters related to the hydrophobic contact area and affinity for immobilised
      C18 chains were determined at temperatures that ranged from 5 to 85 degrees C,
      allowing conformational transitions for the peptides during surface adsorption to
      be monitored. The results demonstrated that all peptides which adopt secondary
      structure in solution also exhibited large changes in their interactive
      properties. Overall, this study demonstrates that the hydrophobic face of each
      amphipathic peptide dominates the binding process and that hydrophobic
      interactions are a major factor controlling the surface induction of secondary
      structure.

PMID- 9650715
TI  - Synthesis and stabilization of amino and carboxy terminal constrained collagenous
      peptides.
AB  - Short collagenous peptides cross-linked at their amino and carboxy termini with
      Lys-Lys-dimer template(s) were synthesized, and the effect of the cross-linking
      on their stabilities was investigated by thermal denaturation experiments. Two
      chemoselective ligations were used for the construction of the amino and the
      carboxy cross-linked peptides. The thermal transition temperature (Tm) and the
      standard free energies (deltaG(o)) of the cross-linked collagenous peptides
      increased, and the thermal stabilization effect corresponded to an elongation by
      two units of the Gly-Pro-Hyp triad. The van't Hoff enthalpy (deltaH(o)) and the
      entropy (deltaS(o)) values of the cross-linked peptides increased with chain
      elongation, although the increments were smaller than those of the linear
      peptides. When the same chain lengths were compared, the deltaH(o) was increased
      and the deltaS(o) was nearly the same or increased by the cross-linking. These
      results suggest that the cross-linking of the collagenous peptides with the Lys
      Lys-dimer template(s) for stabilization contributes to the enthalpic effect,
      rather than the entropic effect.

PMID- 9650716
TI  - NMR and quenched molecular dynamics studies of superpotent linear and cyclic
      alpha-melanotropins.
AB  - Conformational searching, computer simulations, synthesis and NMR are used on a
      variety of alpha melanocyte-stimulating hormone (alpha-MSH) analogues to
      understand the physical characteristics required for biological potency. Peptides
      I (Ac-[Nle4,Asp5,D-Phe7,Lys10]alpha-MSH(4-10)-NH2), II (Ac-c[Nle4,Asp5,D
      Phe7,Lys10]alpha-MSH(4-10)-NH2) and III (Ac-[Nle4,Asp5,D-Phe7,Dap10]alpha-MSH(4
      10)-NH2 all show very similar conformational properties (backbone and side-chain
      torsional angles), and all display high biological potencies. The modeling
      results for these compounds are supported by the NMR data. Peptide IV (Ac
      c[Nle4,Asp5,D-Phe7,Dap10]alpha-MSH(4-10)-NH2) appears to have a markedly
      different conformation and has decreased biological potency.

PMID- 9650717
TI  - Lanthionine macrocyclization by in situ activation of serine.
AB  - The present report details a straightforward, solid-phase approach to
      cyclolanthionine peptides. After stepwise assembly of the linear sequence and
      transformation of a single exposed serine to bromoalanine using P(Ph)3/CBr4, the
      detritilation of a cysteine side-chain sets the stage for a base-promoted
      macrocyclization. The entire procedure can be carried out in a solid-phase vessel
      using conventional 9-fluorenylmethyloxycarbonyl/tert-butyl-based chemistry and is
      amenable to automated format. The utility of this novel procedure is demonstrated
      by the synthesis of two previously reported lanthionine-containing cyclic
      peptides.

PMID- 9650718
TI  - Characterization of the thiol/disulfide chemistry of peptides corresponding to
      the 603-609 disulfide loop of the human immunodeficiency virus (HIV) envelope
      glycoprotein gp41.
AB  - The redox chemistry of two synthetic model peptides for the 603-609 disulfide
      loop found in envelope glycoprotein gp41 of the human immunodeficiency virus type
      1 (HIV-1) are reported. The two peptides: N-Ac-Trp-Gly-Cys-Ser-Gly-Lys-Leu-Ile
      Cys-Thr-Thr-NH2 (I) and N-Ac-Trp-Gly-Cys-Ser-Gly-Arg-His-Ile-Cys-Thr-Thr-NH2 (II)
      were synthesized by the solid phase method. Peptide I corresponds to amino acids
      601-611 of gp41 of the North American/European strain of HIV-1. Peptide II
      incorporates amino acid replacements frequent in African HIV-1 isolates. The
      redox chemistry of the disulfide bonds in the two peptides was characterized in
      aqueous and aqueous/urea solution by studying their thiol-disulfide exchange
      reactions with the tripeptide glutathione (GSH). GSH reacts with the disulfide
      bonds to form mixed disulfides, which in turn react with another molecule of GSH
      to give the dithiol form of the peptide and GSSG. Equilibrium constants were
      determined for each step and for the overall reduction reactions. Redox
      potentials of -0.246V and -0.241V were calculated from the equilibrium constants
      for the disulfide bonds in peptides I and II in aqueous solution at 25 degrees C
      and pH 7.0. The overall equilibrium constants are less in 8 M urea solution,
      which indicates a stabilization of the reduced, dithiol form of both peptides by
      secondary structure which can be denatured by urea. This conclusion is supported
      by nuclear Overhauser enhancement data obtained from 2D-ROESY NMR spectra which
      provide evidence of elements of secondary structure for the reduced forms of both
      peptides. The results are discussed in terms of a protein disulfide isomerase
      catalyzed reduction of the disulfide bond in gp41.

PMID- 9650720
TI  - A comparative conformational analysis of thimet oligopeptidase (EC 3.4.24.15)
      substrates.
AB  - The specificity of thimet oligopeptidase (EC 3.4.24.15) (TOP 24.15) does not
      agree with theoretical models devised to explain the specificity characteristic
      of peptidases toward certain sequences of amino acid residues. According to
      previous studies peptide chains hydrolyzed by TOP 24.15 adopt similar main chain
      conformations, although with different and in some cases small probabilities of
      occurrence in aqueous solution. To determine specific structural features
      recognized by TOP 24.15, a conformational search including eight polypeptides
      with known susceptibilities for catalytic hydrolysis was executed and the
      distribution of each main chain conformation found in the search was tabulated.
      Two sets of main chain conformations were selected, those common to all peptides
      in the study and those common only to substrates of TOP 24.15. The former set is
      very small and includes mainly extended conformations. In contrast, the latter
      set is large and its conformations are coiled and exhibit sharp turns coincident
      with positions of hydrolysis by TOP 24.15. These results indicate a possible
      basis for the selectivity of TOP 24.15.

PMID- 9650719
TI  - Analysis of synthetic peptides by capillary zone electrophoresis in
      organic/aqueous buffers.
AB  - Whereas synthetic peptides have been routinely analyzed for purity by reverse
      phase high performance liquid chromatography (RPHPLC) for a number of years, it
      is only in the last decade that the use of capillary zone electrophoresis (CZE)
      in aqueous buffers has been taken advantage of as an orthogonal method for the
      detection of impurities. However, we have found that hydrophobic amino acids and
      peptides often migrate as very broad, tailing absorbances or even precipitate in
      the aqueous buffers during CZE analysis. As a result, alternative buffer systems
      containing organic modifiers were sought. Varying concentrations of acetonitrile,
      methanol and isopropanol in sodium phosphate and triethylammonium phosphate
      buffers were used to study their effects on the electrophoretic migration of
      several synthetic peptides [gonadotropin releasing hormone (GnRH), corticotropin
      releasing factor (CRF) and analogs] and an enantiomeric synthetic amino acid. The
      organic/aqueous buffers used to obtain the best conditions for separation of
      porcine gonadotropin-releasing hormone (GnRH) and chicken II GnRH were then used
      to optimize a separation of nine native forms of GnRH decapeptides.
      Interestingly, several of these GnRHs have identical formal charges and yet could
      be separated. This suggests a mixed mechanism of separation that discriminates
      not only on the basis of peptide charge and structure but also of adsorptive
      properties (Van der Waals forces, dipole-dipole interactions and hydrogen
      bonding) of the capillaries.

PMID- 9650721
TI  - Structure of cyclic peptides: the crystal and solution conformation of cyclo(Phe
      Phe-Aib-Leu-Pro).
AB  - A solid-state and solution conformation analyses of the cyclopentapeptide
      cyclo(Phe-Phe-Aib-Leu-Pro) has been carried out by X-ray diffraction and nuclear
      magnetic resonance techniques. The structure of the hexagonal crystals, grown
      from a methanol solution [a = b = 16.530(4) A, c = 21.356(9) A, space group
      P6(5), Z = 6], shows the presence of one intramolecular N-H ..O=C hydrogen bond
      with the formation of a gamma-turn (C7). The Aib3 residue, at the center of the
      gamma-turn, presents unexpected values of the torsion angles [phi = 70.5 degrees
      and psi = -73.8 degrees], which have been observed only once before for this
      helicogenic residue. A cis peptide bond occurs between Leu4 and Pro5; all other
      peptide bonds are trans. The overall conformation for the cyclopentapeptide with
      one cis-peptide bond on one side and an intramolecular gamma-turn on the opposite
      side results in an equatorial topology of the side-chains of the Phe1, Phe2 and
      Leu4 residues. Indeed, the Calpha-Cbeta and Cbeta-Cgamma bonds of these residues
      lie approximately in the mean plane of the cyclic ring system. The structure is
      compared with data in the literature on cyclic pentapeptides. In addition the Pro
      Phe-Phe moiety shows a conformation similar to that observed in other larger
      cyclic bioactive peptides, which indicates a reduced number of conformations for
      this sequence. The solution study was carried out in three different solvent
      systems: chloroform, acetonitrile and methanol in the temperature interval 220
      300 K. In all three solvents the room temperature spectra show that the peptide
      is conformationally nonhomogeneous. In acetonitrile at low temperatures it is
      possible to reduce the conformational equilibrium to two predominant conformers
      which differ for the cis-trans isomerism of the Leu4-Pro5 peptide bond.

PMID- 9650722
TI  - Soil forming and plant density effects on carrot yield and internal quality.
AB  - The effects of soil forming (SF) and plant density (PD) on the carrot yield, mean
      root weight and internal quality was studied in field experiments in 1993 and
      1994. 'Fontana BZ' carrots were grown in flat land, a narrow ridge, a broad
      ridge, and a compacted broad ridge soil configurations with low (LD) and high
      (HD) target plant densities, four and seven hundred thousand carrots per hectar.
      The total and marketable yields were larger in flat land and narrow ridge than in
      the broad- and compacted broad ridges in 1993 and in 1994 at HD. The number of
      marketable carrots were highest with the flat land soil configurations in both
      years. A dry spring in 1993 favored flat land growing conditions; in ridges the
      fine sand dried quickly. SF did not influence the mean weight of a marketable
      carrot in 1993, but in 1994 the narrow ridge configuration resulted in heavier
      carrots than the flat land or broad ridge growing conditions. In the climatically
      more unfavorable year of 1993, SF and PD affected quality; dry matter was lower
      in flat land than in the ridges. At HD, the flat land soil configuration produced
      higher glucose and fructose than carrots grown in the narrow and broad ridges.
      Dietary fiber and vitamin C were higher in narrow ridge than in compacted broad
      ridge grown carrots. At LD the flat land and broad ridge produced highest and
      compacted broad ridge the lowest beta-carotene contents; alpha-carotene was
      higher at LD than at HD.

PMID- 9650723
TI  - Mineral binding capacity of dephytinized insoluble fiber from extruded wheat, oat
      and rice brans.
AB  - Insoluble fiber fractions from raw and extruded oat, rice and wheat brans were
      isolated and phytate removed. In vitro mineral binding studies were performed
      utilizing copper (Cu2+), calcium (Ca2+) and zinc (Zn2+) ions, which were added
      individually to enzymatically treated (Prosky et al., 1985), acid washed
      insoluble fiber residues from oat, rice and wheat brans. The enzymatic digestion
      step with alpha-amylase, protease and amyloglucosidase served to remove protein
      and starch from the samples. Mineral binding studies were performed on the
      insoluble fiber residue. Mineral content was determined by flame atomic
      absorption spectroscopy. Raw brans served as controls. A twin-screw extruder
      Model DNDG-62/20D, manufactured by Buhlerag (CH-9240, Uzwil, Switzerland) was
      utilized. The objectives of the study were to determine the total Cu2+, Ca2+ and
      Zn2+ binding capacity of the dephytinized insoluble fiber from each bran; and to
      determine if extrusion screw speed affected the brans' insoluble fiber mineral
      binding capacity. Although dephytinized, the brans' insoluble fiber fraction
      bound Cu2+, Ca2+ and Zn2+ ions. Oat bran bound more Cu2+, Ca2+ and Zn2+ than
      wheat bran, which bound more than rice bran. Extrusion processing did not affect
      the brans' insoluble fiber binding capacity to bind Cu2+. However, it increased
      the binding capacity of Ca2+ and Zn2+ of the insoluble fiber fraction from rice
      and oat brans.

PMID- 9650724
TI  - Evaluation of growth of Neosartorya spp. on some Nigerian fruit products.
AB  - Growth of Neosartorya fischeri, N. fischeri var. spinosa and N. quadricincta on
      inoculated fruit juice agars (FJAs) consisting of 1% agar and juices from mango
      (MJA), orange (OJA) and pineapple (PJA) containing various levels of added
      sucrose was studied in terms of the average number of colonies produced by their
      ascospores, time (days) required before colonies were formed and developed to
      confluent mycelial mat as well as the level of reproductive spores produced. The
      means of the number of colonies on PJA and OJA without added sucrose were
      significantly (p = 0.05) higher than that of MJA. Addition of sucrose at levels
      of 10% to PJA, 11.5% to OJA and 9% to MJA increased the numbers of colonies
      whereas sucrose levels of 30% or more in PJA, 31.5% or more in OJA and 29% or
      more in MJA decreased the number of colonies produced. At any level of added
      sucrose to FJAs, a significant (p = 0.05) delay occurred before the colonies were
      formed and developed to confluent mycelial mat except in PJA containing 10%
      sucrose. All cultures produced abundant cleistothecia on all FJAs without added
      sucrose. Addition of sucrose at levels of 30% to PJA, 31.5% to OJA and 29% to MJA
      resulted in the production of abundant conidial heads with a corresponding
      decrease in the proportion of cleistothecia.

PMID- 9650725
TI  - Hypolipidemic effect of flavonoids from Solanum melongena.
AB  - Flavonoids extracted from the fruits of Solanum melongena (Brinjal) orally
      administered at a dose of 1 mg/100 g BW/day showed significant hypolipidemic
      action in normal and cholesterol fed rats. HMG CoA reductase activity was found
      to be enhanced, while activities of glucose-6-phosphate dehydrogenase and malate
      dehydrogenase were significantly reduced. Activities of lipoprotein lipase and
      plasma LCAT showed significant enhancement. A significant increase in the
      concentrations of hepatic and fecal bile acids and fecal neutral sterols was also
      observed indicating a higher rate of degradation of cholesterol.

PMID- 9650726
TI  - Composition and functional properties of protein isolates obtained from
      commercial legumes grown in northern Spain.
AB  - Pea (Pisum sativum), faba bean (Vicia faba) and soybean (Glycine max) seeds were
      characterized, and protein isolates were prepared following an isoelectric point
      precipitation procedure. Soybean seeds showed the highest protein content (36.7%)
      and carbohydrate was the major constituent in the pea (59.4%) and the faba bean
      seeds (52.1%). Protein contents were higher than 80% in all the protein isolates.
      The amino acid contents in the protein isolates were, in general, higher than
      those in their own starting seeds. The antinutritional factor contents were
      reduced after the protein isolate preparation. The highest reductions achieved
      for tannins were 95% in the faba bean protein isolate, and for phytates (45%) and
      trypsin inhibitor activity (46%) in the pea protein isolate. Haemagglutinating
      activity was not detected in any of the protein isolates. Minimum solubility
      values were observed at a pH range between 4.0 and 6.0, and maximal solubilities
      were obtained at basic pH values. The faba bean protein isolate showed the
      highest water and oil absorption capacities, and the best gelling properties. The
      soybean protein isolate had the best foam expansion capacity. Thus, the protein
      isolates had an improvement in some of the characteristics compared to their
      original seeds with lower contents in tannins, phytates and haemagglutinating
      activity, but had weak functional properties.

PMID- 9650727
TI  - Cultivar and processing effects on the pasting characteristics, tannin content
      and protein quality and digestibility of cowpea (Vigna unguiculata).
AB  - Four popular West African local cultivars of cowpea (Vigna unguiculata), with
      distinctly different seed coat colors, were evaluated for their relative
      amylograph pasting characteristics, condensed tannin content, in vitro protein
      digestibility and Tetrahymena protein efficiency ratio (t-PER). The effects of
      roasting and dehulling on these properties were also determined. There were wide
      variations in the hot paste viscosity characteristics of the different cultivars
      studied. The raw cowpea flour samples exhibited maximum paste viscosities ranging
      between 260 Brabender Units (BU) for the Mottled cultivar and 460 BU for the
      cream-colored Blackeye cultivar. Cowpea cultivars with the greatest peak
      viscosities showed low stabilities to extended cooking. Roasting depressed paste
      viscosity properties of all the cowpea cultivars studied. Tannin concentrations
      were 0.3-6.9 and 7.2-116 mg CE/g flour from whole cowpea seeds and seed coats
      respectively, increasing with intensity of seed color. Although dehulling removed
      98% of the tannin content of raw cowpeas, improvement in protein quality as a
      result of dehulling was observed for only the highly-pigmented Maroon-red
      variety. Roasting significantly improved digestibility and more than doubled the
      t-PER of all cowpea cultivars studied. Roasted cowpeas possess adequate
      nutritional and functional qualities as protein supplements in cereal-based
      weaning foods. However, it appears that dehulling is necessary to enhance the
      nutritional quality of the highly pigmented cultivars of cowpea.

PMID- 9650728
TI  - Effect of spraying selected pesticides on the contents of specified minerals in
      cabbage.
AB  - The present study was conducted to assess the effect of spraying of pesticides on
      the content of minerals in cabbage harvested at varying waiting periods (0, 7, 14
      and 21 days) after spraying. The amounts of phosphorus and zinc in cabbage were
      significantly (p < 0.05) decreased while those of iron, calcium and potassium
      were significantly (p < 0.05) increased by the sprayings of pesticides. At
      varying waiting periods after the spraying of pesticides calcium, phosphorus,
      zinc and potassium contents of cabbage were found to be decreased remarkably (p <
      0.05) while the content of iron was increased significantly (p < 0.05). Between
      the two pesticides, the spraying of endosulfan exerted a more pronounced effect
      in altering the contents of minerals than the spraying of malathion.

PMID- 9650729
TI  - Effect of soy-fortification method on the fermentation characteristics and
      nutritional quality of fermented maize meal.
AB  - Studies were conducted to develop an appropriate household/small-scale enterprise
      level technique for the production of soy-fortified fermented maize dough (or
      meal) by comparing different treatments, processing methods and fortification
      levels. The effects of fortification method of the Ghanaian traditional fermented
      maize dough with raw or heat-treated whole soybeans and full-fat soyflour at 0%,
      10% and 20% replacement levels, on the rate of fermentation and product quality
      were investigated. Sensory characteristics, trypsin inhibitor activity, amino
      acid pattern, proximate composition and hot paste viscosity were used as the
      indices of quality. Addition of whole soybeans to maize before milling and
      fermentation reduced the fermentation time by 60% while increasing the protein
      content by 24% and 70% respectively for 10% and 20% levels of fortification. A
      significant improvement was also achieved in the amino acids pattern of the
      fortified dough. However, raw whole soybeans imparted an undesirable color and
      beany flavor and an appreciable concentration of trypsin inhibitor activity (TIA)
      to the dough. Boiling soybeans for 20 min before incorporation into the maize for
      milling and fermentation was found necessary for desirable flavor and low levels
      of TIA. Little or no changes in the pasting viscosity characteristics occurred in
      samples containing boiled soybeans, while the usual method of fortifying maize
      meal with soy flour was found to severely depress the pasting viscosity
      characteristics and drastically reduced the acidity of the fermented dough. Based
      on the findings of the study, the most appropriate technique for the production
      of soy-fortified high protein fermented maize dough has been suggested to involve
      incorporation of boiled whole soybeans in soaked maize before milling and
      fermentation for improved sensory characteristics, enhanced nutritive value and
      optimal functional properties.

PMID- 9650730
TI  - Energy cost and running mechanics during a treadmill run to voluntary exhaustion
      in humans.
AB  - The aim of the present study was to examine the physiological and mechanical
      factors which may be concerned in the increase in energy cost during running in a
      fatigued state. A group of 15 trained triathletes ran on a treadmill at
      velocities corresponding to their personal records over 3000m [mean 4.53 (SD
      0.28) m x s(-1)] until they felt exhausted. The energy cost of running (CR) was
      quantified from the net O2 uptake and the elevation of blood lactate
      concentration. Gas exchange was measured over 1 min firstly during the 3rd-4th
      min and secondly during the last minute of the run. Blood samples were collected
      before and after the completion of the run. Mechanical changes of the centre of
      mass were quantified using a kinematic arm. A significant mean increase [6.9 (SD
      3.5)%, P < 0.001] in CR from a mean of 4.4 (SD 0.4) J x kg(-1) x m(-1) to a mean
      of 4.7 (SD 0.4) J x kg(-1) x m(-1) was observed. The increase in the O2 demand of
      the respiratory muscles estimated from the increase in ventilation accounted for
      a considerable proportion [mean 25.2 (SD 10.4)%] of the increase in CR. A mean
      increase [17.0 (SD 26.0)%, P < 0.05] in the mechanical cost (CM) from a mean of
      2.36 (SD 0.23) J x kg m(-1) to a mean of 2.74 (SD 0.55) J x kg(-1) x m(-1) was
      also noted. A significant correlation was found between CR and CM in the non
      fatigued state (r=0.68, P < 0.01), but not in the fatigued state (r=0.25, NS).
      Furthermore, no correlations were found between the changes (from non-fatigued to
      fatigued state) in CR and the changes in CM suggesting that the increase in CR is
      not solely dependent on the external work done per unit of distance. Since step
      frequency decreased slightly in the fatigued state, the internal work would have
      tended to decrease slightly which would not be compatible with an increase in CR.
      A stepwise regressions showed that the changes in CR were linked (r=0.77, P <
      0.01) to the changes in the variability of step frequency and in the variability
      of potential cost suggesting that a large proportion of the increase in CR was
      due to an increase in the step variability. The underlying mechanisms of the
      relationship between CR and step variability remains unclear.

PMID- 9650731
TI  - Physiological and performance responses to supplementation with thiamin and
      pantothenic acid derivatives.
AB  - The purpose of this study was to investigate the physiological and performance
      responses to supplementation with allithiamin and pantethine. On two separate
      occasions, six highly trained cyclists [maximum O2 consumption or VO2max 61.8
      (2.1) ml x kg(-1) x min(-1)] performed a 50-km steady-state ride on a cycle
      ergometer at a workload corresponding to approximately 60% of VO2max followed by
      a 2000-m time trial. For 7 days prior to each ride, subjects daily ingested
      either a placebo (PL) or a combination of 1 g of allithiamin and 1.8 g of a
      55%/45% pantethine/pantothenic acid compound (AP). Treatments were administered
      using a randomized, double-blind, counter-balanced design. During the 50km ride,
      measures of heart rate, respiratory gas exchange and ratings of perceived
      exertion were recorded at 5, 15, 25, 35 and 45 km. Blood samples were collected
      at 10, 20, 30, 40 and 50 km and analyzed for lactate, glucose and free fatty
      acids. Blood samples for the analysis of lactate were also collected 3 and 5 min
      after the completion of the 2000-m time trial. There were no significant
      differences in any of the measured parameters between experimental conditions.
      Time to complete the 2000-m time trial was also not significantly different
      between experimental conditions [PL 178.2 (8.4), AP 170.7 (10.2) s; P=0.58].
      These results suggest that, despite the reported enhanced absorption properties,
      supplementation with allithiamin and pantethine does not alter exercise
      metabolism or exercise performance.

PMID- 9650732
TI  - The mathematics of breaking away and chasing in cycling.
AB  - In cycling stage races a small group of riders will often form a "breakaway" and
      establish a lead over the main group. This paper examines the factors that affect
      the likelihood of success for the breakaway. A mathematical approach is used,
      drawing on a model of cycling previously developed and validated (Olds et al. J
      Appl Physiol 78:1596 1611, 1995). In a breakaway group, the power required to
      overcome air resistance is reduced because the lead can be shared, with trailing
      riders sheltering or drafting behind leading riders. The benefit of drafting can
      be quantified as a function of the distance between riders using previously
      obtained data. Of course, this advantage is even greater in the (larger) chasing
      group, so that eventually the chasing group will catch the breakaway, assuming
      identical bicycles and physiological characteristics. The question addressed is:
      what factors determine how great a lead the breakaway must have in order for the
      chasing group to be unable to catch the breakaway before the finish of the race?
      Demand-side simulations show that the critical factors are: the distance
      remaining in the race; the speed of the breakaway group; the number of riders in
      the chasing and breakaway groups: how closely riders in each group draft one
      another; the grade; surface roughness; as well as head- and cross-winds. When
      supply-side physiological factors are incorporated, the maximum sustainable speed
      and maximum lead time can be calculated.

PMID- 9650733
TI  - Electron spin resonance spectroscopic detection of oxygen-centred radicals in
      human serum following exhaustive exercise.
AB  - Free radicals or oxidants are continuously produced in the body as a consequence
      of normal energy metabolism. The concentration of free radicals, together with
      lipid peroxidation, increases in some tissues as a physiological response to
      exercise - they have also been implicated in a variety of pathologies. The
      biochemical measurement of free radicals has relied in the main on the indirect
      assay of oxidative stress by-products. This study presents the first use of
      electron spin resonance (ESR) spectroscopy in conjunction with the spin-trapping
      technique, to measure directly the production of radical species in the venous
      blood of healthy human volunteers pre- and post-exhaustive aerobic exercise.
      Evidence is also presented of increased lipid peroxidation and total antioxidant
      capacity post-exercise.

PMID- 9650734
TI  - Effects of in vivo-like activation frequency on the length-dependent force
      generation of skeletal muscle fibre bundles.
AB  - It is known that a range of firing frequencies can be observed during in vivo
      muscle activity, yet information is lacking as to how different in vivo-like
      frequencies may affect force generation of skeletal muscle. This study examined
      the effects of constant (CSF, constant within one contraction) and decreasing
      stimulation frequencies (DSF) on mean sarcomere length-force characteristics of
      rat gastrocnemius medialis fibre bundles. The CSF resulted in an optimal mean
      sarcomere length (lso) of 2.30 (SEM 0.02), 2.46 (SEM 0.03), 2.76 (SEM 0.03) and
      more than 2.99 (SEM 0.07) lm, for 100, 50, 30 and 15 Hz, respectively. Compared
      to 100-Hz stimulation, both lso and the ascending limb of the relationship
      significantly shifted to higher lengths with lower frequencies. No shift was
      encountered for the initial part of the descending limb. The DSF reduced the
      frequency-induced shift to higher mean lengths [lso 2.33 (SEM 0.02), 2.52 (SEM
      0.08) and more than 2.92 (SEM 0.10) microm, respectively, for 50, 30 and 15 Hz].
      No effect of activation time on length-force characteristics was observed. It was
      concluded from these studies that the frequency and history of stimulation is a
      major determinant of the length-force characteristics of muscle fibre bundles,
      and should be taken into account when analysing animal and human locomotion. The
      previously observed frequency-induced shift in whole muscle length-force
      relationship resides mainly at the level of fibre bundles.

PMID- 9650735
TI  - Heritability of running economy: a study made on twin brothers.
AB  - Running economy (RE), defined as the steady-state of oxygen uptake (VO2) for a
      given running velocity, is a factor of sports performance the genetic component
      of which has seldom been reported to date. We studied this component using a
      heritability index (HI) in a group of 32 male twins, 8 monozygotic (MZ) and 8
      dizygotic (DZ) pairs, all sportsmen with similar perinatal and environmental
      backgrounds. Zygocity was determined by the identity of erythrocytic antigenic,
      protein and enzymatic polymorphism, and human leucocyte antigen serologic types
      between co-twins. The subjects exercised twice on a treadmill, once until
      exhaustion and again at submaximal intensities. Pulmonary gas exchange was
      measured continuously using an automatic analyser system during both tests. Blood
      samples were obtained during the recovery period to determine lactate
      concentrations. No significant differences were observed between MZ and DZ, in
      respect of RE at any speed or in maximal VO2 relative to body mass. Nevertheless,
      significant HI (P < 0.05) was found in maximal lactate concentrations (HI=0.75)
      and in respiratory equivalent for oxygen at two speeds, 7 km x h(-1) HI=0.71) and
      8 km x h(-1) (HI=0.79), differences which probably suggest that there are
      differences in RE. In conclusion, we did not detect a genetic component in RE or
      in maximal oxygen uptake, but a genetic component for markers of anaerobic
      metabolism was present.

PMID- 9650736
TI  - Effect of restricted blood flow on exercise-induced hormone changes in healthy
      men.
AB  - To test the influence of the accumulation of metabolites on exercise-induced
      hormone responses, plasma concentrations of cortisol, growth hormone (GH),
      insulin, testosterone, thyrotropin (TSH), free thyroxine (fT4) and
      triiodothyronine (T3) were compared during exercise performed under normal
      conditions (control) and under conditions of restricted blood flow of exercising
      leg muscles (ischaemia) in nine healthy young men. Blood supply was reduced by
      15%-20% by the application of 50 mmHg external pressure over the exercising leg.
      During 45-min cycling exercise during ischaemia the increase in GH concentration
      was twice as large as under normal conditions. Despite the below-threshold
      exercise intensity for activation of the pituitary-adrenocortical system under
      normal exercise conditions ischaemic exercise elicited cortisol and T3 responses
      (concentration increases of 83% and 9.5%, respectively). Ischaemic exercise
      attenuated the decrease of plasma insulin concentration found under normal
      conditions. The concentrations of testosterone, TSH and fT4 were not changed
      significantly during exercise performed in either condition. The results support
      the suggested essential role of muscle metaboreceptors in the control of hormone
      responses during muscle activity.

PMID- 9650737
TI  - Effects of beta-adrenoceptor-blockade on stress-induced adrenocorticotrophin
      release in humans.
AB  - We investigated the mechanisms of stress-induced alterations in
      adrenocorticotrophin (ACTH) release. Tandem parachutists received either a
      placebo or the beta-adrenoceptor antagonist propranolol prior to a first time
      parachute jump. Blood samples were drawn 4 h before, immediately after, and 1 h
      after the jump. Cortisol and catecholamine concentrations displayed a significant
      stress-induced increase in both groups. The ACTH plasma concentrations
      significantly increased in the placebo and the propranolol group, with
      significantly more pronounced changes in the propranolol-treated subjects
      compared to the placebo group. These data demonstrated a stress-induced increase
      of ACTH plasma concentrations in humans that was enhanced by beta-blockade.

PMID- 9650738
TI  - Summation of elementary phonomyograms during isometric twitches in humans.
AB  - To study its summation principle, the phonomyogram (PMG) from the first
      interosseus dorsalis muscle was recorded in five subjects during single twitches
      evoked by electrical stimulation over the motor point. By increasing the current
      pulse from threshold to maximal intensity, PMG amplitude increased linearly with
      motor unit recruitment. The twitch amplitude-intensity relationship was also
      linear. The PMG amplitude was therefore linearly related to the external force.
      For all these relationships highly significant correlation coefficients were
      found. These relationships were interpreted as being a consequence of an orderly
      recruitment, although, contrary to what happens during voluntary contraction, the
      largest and strongest motor units were recruited before the smallest and weakest
      ones during axon electrical stimulation. The PMG onset always preceded twitch
      onsets as indicated by latency measurements [mean 3.2 (SD 1.3) ms versus 11.5 (SD
      3.9) ms, respectively]. Moreover, PMG and twitch latencies may have been
      significantly reduced by recruitment, suggesting that orderly recruitment
      influenced both PMG amplitude and occurrence. These results were interpreted as
      being the result of the summation of elementary PMG from every contracting motor
      unit and the stiffness change of the muscle medium occurring with recruitment.

PMID- 9650739
TI  - The influence of either no fluid or carbohydrate-electrolyte fluid ingestion and
      the environment (thermoneutral versus hot and humid) on running economy after
      prolonged, high-intensity exercise.
AB  - This study investigated the effects on running economy (RE) of ingesting either
      no fluid or an electrolyte solution with or without 6% carbohydrate
      (counterbalanced design) during 60-min running bouts at 80% maximal oxygen
      consumption (VO2max). Tests were undertaken in either a thermoneutral (22-23
      degrees C; 56-62% relative humidity, RH) or a hot and humid natural environment
      (Singapore: 25-35 degrees C; 66-77% RH). The subjects were 15 young adult male
      Singaporeans [VO2max=55.5 (4.4 SD) ml kg(-1) min(-1)]. The RE was measured at 3 m
      s(-1) [65 (6)% VO2max] before (RE1) and after each prolonged run (RE2). Fluids
      were administered every 2 min, at an individual rate determined from prior tests,
      to maintain body mass (group mean=17.4 ml min(-1)). The VO2 during RE2 was higher
      (P < 0.05) than that during the RE1 test for all treatments, with no differences
      between treatments (ANOVA). The mean increase in VO2 from RE1 to RE2 ranged from
      3.4 to 4.7 ml kg(-1) min(-1) across treatments. In conclusion, the deterioration
      in RE at 3 m s(-1) (65% VO2max) after 60 min of running at 80% VO2max appears to
      occur independently of whether fluid is ingested and regardless of whether the
      fluid contains carbohydrates or electrolytes, in both a thermoneutral and in a
      hot, humid environment.

PMID- 9650740
TI  - The effect of severe eccentric exercise-induced muscle damage on plasma elastase,
      glutamine and zinc concentrations.
AB  - The aim of this study was to determine if severe exercise-induced muscle damage
      alters the plasma concentrations of glutamine and zinc. Changes in plasma
      concentrations of glutamine, zinc and polymorphonuclear elastase (an index of
      phagocytic cell activation) were examined for up to 10 days following eccentric
      exercise of the knee extensors of one leg in eight untrained subjects. The
      exercise bout consisted of 20 repetitions of electrically stimulated eccentric
      muscle actions on an isokinetic dynamometer. Subjects experienced severe muscle
      soreness and large increases in plasma creatine kinase activity indicative of
      muscle fibre damage. Peak soreness occurred at 2 days post-exercise and peak
      creatine kinase activity [21714 (6416) U x l(-1) mean (SEM)] occurred at 3 days
      post-exercise (P < 0.01 compared with pre-exercise). Plasma elastase
      concentration was increased at 3 days post-exercise compared with pre-exercise (P
      < 0.05), and is presumably indicative of ongoing phagocytic leucocyte
      infiltration and activation in the damaged muscles. There were no significant
      changes in plasma zinc and glutamine concentrations in the days following
      eccentric exercise. We conclude that exercise-induced muscle damage does not
      produce changes in plasma glutamine or zinc concentrations despite evidence of
      phagocytic neutrophil activation.

PMID- 9650741
TI  - Effects of arm and leg loading on sprint performance.
AB  - The effects of loading on sprint kinematics were examined in 24 male students.
      The moment of inertia of either the arms or legs was increased by up to 50% of
      their unloaded values and the time for distances of 0.5-15 m and 15-30 m from a
      sprint start was measured. An increase in leg loading was associated with a
      gradual decrease in velocity of both sprint phases, while the change associated
      with arm loading was modest and significant only in the second phase. The
      decrease in sprint velocity was predominantly due to a reduction in stride rate,
      while the stride length remained almost unchanged. It was concluded that leg
      loading affected sprint velocity more than arm loading, and also that the
      velocity was reduced due to a decrease in the stride rate rather than in the
      stride length.

PMID- 9650742
TI  - Oxygen uptake during moderate intensity running: response following a single bout
      of interval training.
AB  - Eight male endurance runners [mean+/-(SD): age 25 (6) years; height 1.79 (0.06)
      m; body mass 70.5 (6.0) kg; % body fat 12.5 (3.2); maximal oxygen consumption
      (VO2max 62.9 (1.7) ml x kg(-1) x min(-1)] performed an interval training session,
      preceded immediately by test 1, followed after 1 h by test 2, and after 72 h by
      test 3. The training session was six 800-m intervals at 1 km x h(-1) below the
      velocity achieved at VO2max with 3 min of recovery between each interval. Tests
      1, 2 and 3 were identical, and included collection of expired gas, measurement of
      ventilatory frequency (fr), heart rate (Fc)r rate of perceived exertion (RPE),
      and blood lactate concentration ([La-]B) during the final 5 min of 15 min of
      running at 50% of the velocity achieved at V02max (50% v-VO2max). Oxygen uptake
      (VO2), ventilation (VE), and respiratory exchange ratio (R) were subsequently
      determined from duplicate expired gas collections. Body mass and plasma volume
      changes were measured preceding and immediately following the training session,
      and before tests 1-3. Subjects ingested water immediately following the training
      session, the volume of which was determined from the loss of body mass during the
      session. Repeated measures analysis of variance with multiple comparison (Tukey)
      was used to test differences between results. No significant differences in body
      mass or plasma volume existed between the three test stages, indicating that the
      differences recorded for the measured parameters could not be attributed to
      changes in body mass or plasma volume between tests, and that rehydration after
      the interval training session was successful. A significant (P < 0.05) increase
      was found from test 1 to test 2 [mean (SD)] for VO2 [2.128 (0.147) to 2.200
      (0.140) l x min(-1)], fc [125 (17) to 132 (16) beats x min(-1)], and RPE [9 (2)
      to 11 (2)]. A significant (P < 0.05) decrease was found for submaximal R [0.89
      (0.03) to 0.85 (0.04)]. These results suggest that alterations in VO2 during
      moderate-intensity, constant-velocity running do occur following heavy-intensity
      endurance running training, and that this is due to factors in addition to
      changed substrate metabolism towards greater fat utilisation, which could explain
      only 31% of the increase in VO2.

PMID- 9650743
TI  - Significant changes in VLDL-triacylglycerol and glucose tolerance in obese
      subjects following ten days of training.
AB  - We characterized the effect of ten days of training on lipid metabolism in 6 [age
      37.2 (2.3) years] sedentary, obese [BMI 34.4 (3.0) kg x m(-2)] males with normal
      glucose tolerance. An oral glucose tolerance test was performed prior to and at
      the end of the 10 d of training period. The duration of each daily exercise
      session was 40 min at an intensity equivalent to approximately 75% of the age
      predicted maximum heart rate. Blood measurements were performed after an
      overnight fast, before and at the end of the 10 d period. Plasma triacylglycerol
      was significantly (p < 0.05) reduced following exercise training (2.15+/-0.29 vs.
      1.55+/-0.28 mmol x l(-1)). Very low density lipoprotein-triacylglycerol was also
      significantly (p < 0.05) reduced (1.82+/-0.3 vs. 1.29+/-0.29 mmol x l(-1)). No
      significant changes in high density lipoprotein-cholesterol were observed as a
      result of training. Following training fasting plasma glucose and fasting plasma
      insulin were significantly reduced [Glucose: 5.9 (0.2) mmol x l(-1) vs. 5.3
      (0.22) mmol x l(-1) (p < 0.05); Insulin 264.3 (53.8) rho x mol x l(-1) vs. 200.9
      (30.1) rho x mol x l(-1), p=0.05]. The total area under the glucose curve during
      the OGTT decreased significantly (p < 0.05). These preliminary data suggest that
      short-term exercise, without concomitant loss of body mass, induces favorable
      changes in plasma triacylglycerol, and very low density lipoprotein
      triacylglycerol and glucose tolerance but has no effect on high density
      lipoprotein-cholesterol.

PMID- 9650744
TI  - Prolonged intermittent high intensity exercise impairs neuromuscular performance
      of the knee flexors.
AB  - This study investigated the effect of prolonged intermittent high intensity
      exercise upon the isokinetic leg strength and electromechanical delay of the knee
      flexors. Seven male collegiate soccer players were exposed to: (i) a prolonged
      intermittent high intensity exercise task (PIHIET) which required subjects to
      complete a single-leg pedalling task, with the preferred limb, (75 rpm for all
      constant-load portions of the task) consisting of 48 x 1.8 minute cycles of
      exercise, and (ii) a control task consisting of no exercise. Pre-, mid- and post
      PIHIET gravity corrected indices of knee flexion angle-specific torque (0.44 rad
      knee flexion (AST); 0 rad=full knee extension; [1.05 rad x s(-1)]) were made for
      both intervention and control limbs. Electromechanical delay (EMD) of the m.
      biceps femoris during supine knee flexion movements was evaluated in the
      preferred leg on both intervention and control days. Repeated measures ANOVAs
      revealed significant condition (intervention; control) by time (pre; mid; post)
      interactions for both knee flexor AST (F[2,12]=4.8; p < 0.03) and EMD
      (F[2,12]=4.1; p < 0.05). AST was observed to decrease by 16% and EMD increase by
      30% pre to post intervention. These observations suggest an impairment of
      neuromuscular control and the ability to maintain force generation in the knee
      flexors, near the extremes of the range of motion during prolonged intermittent
      high-intensity exercise activities. Changes of this magnitude may pose a threat
      to the integrity of the knee joint.

PMID- 9650745
TI  - Advanced glycation end products co-localized with astrocytes and microglial cells
      in Alzheimer's disease brain.
AB  - In the previous study [Takeda et al. (1996) Neurosci Lett 221: 17-21], we
      reported that the advanced glycation end products (AGEs) in the external space of
      neuronal perikarya (extraneuroperikaryal AGE deposits) were significantly
      abundant in the Alzheimer's brain. In this study, we investigated the spatial
      relationship of the extraneuroperikaryal AGE (carboxymethyllysine and
      pentosidine) deposits in astrocytes and microglial cells in the Alzheimer's
      disease brain using double immunolabelling for AGEs and astrocyte or microglial
      cell markers. Most of the extraneuroperikaryal AGE deposits were co-localized
      with glial fibrillary acidic protein-positive astrocytes. AGE deposit-bearing
      astrocytes also contained Gomori-positive granules. Furthermore, some of the
      extraneuroperikaryal AGE deposits were co-localized with microglial cells. These
      extraneuroperikaryal AGEs may activate astrocyte and microglia, and play a role
      in pathogenesis of Alzheimer's disease.

PMID- 9650746
TI  - p53 and PTEN gene mutations in gemistocytic astrocytomas.
AB  - The gemistocytic astrocytoma is a histological variant of diffuse astrocytomas
      and is characterised by the presence of large, GFAP-expressing neoplastic
      astrocytes (gemistocytes) and a tendency towards rapid progression to
      glioblastoma. In this study, we analyzed 28 gemistocytic astrocytomas (mean
      fraction of gemistocytes, 35.0+/-9.9%) for mutations in the p53 and PTEN (MMAC1)
      tumour suppressor genes. Single strand conformation polymorphism (SSCP), followed
      by direct DNA sequencing of p53 exons 5-8, revealed a mutation in 23 of 28 (82%)
      cases. Regional analysis of four tumours revealed identical p53 mutations in
      gemistocytic and fibrillary tumour areas. In contrast, none of 15 gemistocytic
      astrocytomas (WHO Grade II) and only two of 11 (18%) anaplastic gemistocytic
      astrocytomas (WHO Grade III) contained a PTEN mutation. Of these, one was a 1 bp
      deletion in codon 345 and the other a 1 bp insertion in intron 4. Differential
      PCR did not reveal homozygous PTEN deletion in any of the tumours analysed. These
      results indicate that p53 mutations are a genetic hallmark of gemistocytic
      astrocytomas, whilst PTEN mutations are absent in low-grade and rare in
      anaplastic gemistocytic astrocytomas.

PMID- 9650747
TI  - Enhanced protein synthesis in the ipsilateral substantia nigra following middle
      cerebral artery occlusion in the rat.
AB  - Following focal cerebral ischemia, neuronal cell death is detected in remote
      areas of the brain, including the ipsilateral thalamus and substantia nigra (SN),
      as well as in the ischemic core. We have investigated protein synthesis in the
      remote areas of rats exposed to focal ischemia using autoradiography. The
      proximal portion of the left middle cerebral artery (MCA) was permanently
      occluded, and at various periods (6 h, 2, 4 and 7 days and 2 and 4 weeks
      following ischemia) animals received a single dose of L-[2,3-3H]valine (6.7
      mCi/kg). Brain sections containing the thalamus and SN were processed for
      autoradiography. In the ipsilateral cerebral cortex and striatum, marked
      impairment of protein synthesis was observed and was never completely recovered
      during the experiment. No changes in protein synthesis in the ipsilateral
      thalamus were detected during the experiment. However, a change in protein
      synthesis was demonstrated in the ipsilateral SN. At 2 days after MCA occlusion,
      incorporation of [3H]valine into the whole zona reticulata of the ipsilateral SN
      was slightly enhanced and the increase became evident at 4 days after ischemia.
      Increased incorporation of [3H]valine began to be localized in the lateral
      portion of the zona reticulata after 7 days and continued up to 4 weeks following
      ischemia. Enhanced protein synthesis during the early stage (2 and 4 days after
      ischemia) may be due to the activated function of the neurons in the zona
      reticulata and that during the late stage (7 days and 2 and 4 weeks) after
      ischemia to astroglial proliferation

PMID- 9650748
TI  - Immunohistochemical study of clathrin in distal myopathy with rimmed vacuoles.
AB  - Clathrin-coated vesicles are involved in three receptor-mediated intracellular
      transport pathways: export from the Golgi apparatus, transfer of lysosomal
      enzymes from the Golgi apparatus to lysosomes, and endocytosis at the plasma
      membrane. Seeking evidence of transport abnormalities in distal myopathy with
      rimmed vacuoles (DMRV), we performed immunohistochemistry for clathrin in muscle
      biopsy specimens from patients with this disorder or other neuromuscular
      disorders, and also in control muscle samples resected in orthopedic procedures.
      While most myofibers from control muscle did not stain for clathrin, some fibers
      revealed finely granular sarcoplasmic staining. In specimens from patients with
      Duchenne and Becker muscular dystrophy, amyotrophic lateral sclerosis, peripheral
      neuropathy, and DMRV, numerous clathrin-positive granules were often scattered
      through the sarcoplasm and seen to a lesser extent in subsarcolemmal regions.
      Quantitative immunohistochemical assessment showed more reactivity for clathrin
      in DMRV than in controls and other diseased muscles, particularly in atrophic
      fibers and type 2 fibers. Not all strongly clathrin-positive muscle fibers
      contained rimmed vacuoles, although most fibers with vacuoles were clathrin
      positive. The result suggests that the lysosome system is activated and receptor
      mediated intracellular transport pathways function appropriately in the muscles
      of DMRV patients.

PMID- 9650749
TI  - Cortical Lewy bodies and Alzheimer-type changes in patients with Parkinson's
      disease.
AB  - We investigated the role of cortical Lewy bodies (LB) and Alzheimer-type changes
      in cognitive impairment in patients with idiopathic Parkinson's disease (PD). We
      evaluated 44 cases for the extent of neuropathological lesions with a CERAD
      neuropathological assessment battery and the stage of dementia using Reisberg's
      global deterioration scale (GDS). Substantia nigra, amygdala, hippocampus and
      cerebral cortex were examined for LB and Alzheimer-type changes. For detection of
      LB, the cortical areas were stained with polyclonal antibodies against ubiquitin
      and tau. We found at least one cortical LB in 93% of cases. Furthermore, 43% of
      the cases had histological findings of definite Alzheimer's disease (AD). The
      association between cognitive impairment and the number of cortical LB and
      Alzheimer-type changes in the amygdala, hippocampus and six selected gyri from
      cerebral cortex were analyzed using stepwise linear regression. In this analysis
      the total number of cortical LB, and the amount of neurofibrillary tangles in the
      temporal cortex remained statistically significant. When the cases with
      neuropathological changes consistent with a diagnosis of AD were excluded, the
      correlation between the total number of cortical LB and cognitive impairment was
      more obvious. A stepwise linear regression analysis in these cases found the
      total number of cortical LB to be the statistically significant predictor of
      cognitive impairment. This study revealed that LB densities in the cortex,
      especially in the temporal neocortex, correlated significantly with the cognitive
      impairment in PD independent of or in addition to Alzheimer-type pathology.

PMID- 9650750
TI  - Phenytoin alters Purkinje cell axon morphology and targeting in vitro.
AB  - In adult mice, administration of the anticonvulsive drug phenytoin caused focal
      swellings along the Purkinje cell axon correlated with ataxia and incoordination
      of movements. In our model, we used murine cerebellar slice cultures to study the
      influence of phenytoin on postnatal Purkinje cell axon differentiation. Almost
      all of our untreated cultures developed to mature-like cerebellar tissue.
      Immunohistochemistry with anti-calbindin-D28k or UCHTI (anti-CD3) antibodies
      revealed numerous Purkinje cell axons in the white matter. In the area of the
      deep cerebellar nuclei, immunolabelled axons formed a large axonal plexus. The
      few neurofilament-positive neurons in this area were densely covered with
      Purkinje cell axon terminals. The synaptophysin immunoreactivity revealed
      connections between the terminals and the neurons of the deep cerebellar nuclei.
      Treatment of cerebellar slice cultures with phenytoin (10-80 microM) for 10-16
      days resulted in focal swellings of different size along the axon. The number of
      swellings increased with an increasing dosage. At concentrations of 40 microM
      phenytoin, Purkinje cell axons seemed to be unable to invade the deep cerebellar
      nuclei, but numerous aberrant, recurrent collaterals could be detected
      immunohistochemically with the two specific Purkinje cell antibodies. Possible
      cytotoxic effects after treatment, such as dendritic degeneration and a decrease
      in the number of immunolabelled Purkinje cells, were observed above 40 microM
      phenytoin. These data suggest that the response of juvenile Purkinje cells is
      dependent upon the dosage of the antiepileptic drug because of morphological
      alterations as well as a misrouting of previously established connections.

PMID- 9650751
TI  - Neurotoxicity evoked by N-methyl-D-aspartate in the organotypic static slice
      cultures of rat cerebral cortices: effect of GABA(A) receptor activation.
AB  - We investigated the neurotoxicity evoked by N-methyl-D-aspartate (NMDA) receptor
      stimulation in the organotypic static slice cultures of rat cerebral cortices. We
      also examined whether the gamma-aminobutyric acid (GABA)A receptor agonist
      muscimol has a protective effect on the NMDA-mediated neurotoxicity in this
      culture system. NMDA-mediated cytotoxicity was evaluated histologically and
      quantified by the measurement of lactate dehydrogenase (LDH) release into the
      culture medium. There was an NMDA-induced, dose-dependent leakage of LDH release
      and neuronal cell death, which were not attenuated by muscimol treatment. The
      results suggested that NMDA neurotoxicity is reproduced in the organotypic
      culture, and that GABA(A) receptor activation exerted no protective action
      against the NMDA cytotoxicity.

PMID- 9650752
TI  - Expression of low-affinity neurotrophin receptor p75NTR in the peripheral nervous
      system of human neuropathies.
AB  - Expression of low-affinity neurotrophin receptor (p75NTR) was
      immunohistochemically examined in the peripheral nerve trunks, dorsal root
      ganglia, sympathetic nerve ganglia and spinal cords in various human neurological
      diseases manifesting peripheral neuropathies. p75NTR was expressed in the nerves
      with axonal degeneration, and was also prominent in the nerves with newly
      regenerating axons. In contrast, axonal pathology tended to reduce the expression
      of p75NTR in the neuronal perikarya of the dorsal root ganglion and sympathetic
      nerve ganglion neurons. In the ventral and lateral horn cells, the p75NTR
      immunoreactivity was not detected in the normal and diseased nerves except for
      amyloid polyneuropathy. These p75NTR expressions in the diseased human peripheral
      nervous tissues would be regulated by an underlying pathology-related process,
      and could play a role in peripheral nerve repair.

PMID- 9650753
TI  - Mapping immunoreactive epitopes in the human peripheral nervous system using
      human monoclonal anti-GM1 ganglioside antibodies.
AB  - A series of monoclonal IgM anti-GM1 ganglioside antibodies has been cloned from
      peripheral blood lymphocytes of patients with multifocal motor neuropathy and
      Guillain-Barre syndrome. In solid-phase immunoassay, the antibodies react with
      GMI, and also in differing degrees to the structurally related glycolipids asialo
      GM1 (GA1) and GD1b. Here we describe the binding patterns of six human anti-GM I
      antibodies to epitopes within the human nervous system. Antibodies were observed
      to bind to motor neurons and spinal grey matter, dorsal and ventral spinal roots,
      dorsal root ganglion neurons, nodes of Ranvier, neuromuscular junctions and
      skeletal muscle. The distribution of immunoreactive epitopes, which included
      sensory structures, extended beyond those sites conventionally regarded as
      pathologically affected in anti-GM1 antibody-associated motor nerve syndromes.
      This undermines a model of disease pathogenesis based solely on antigen
      distribution. Factors other than the presence or absence of antigen, such as the
      local ganglioside topography, antibody penetration into, and pathophysiological
      vulnerability of a particular site may also influence the clinicopathological
      outcome of anti-GM1 antibody-mediated autoimmune attack.

PMID- 9650754
TI  - Expression of retinoblastoma gene product and p21 (WAF1/Cip 1) protein in
      gliomas: correlations with proliferation markers, p53 expression and survival.
AB  - Using immunohistochemistry we evaluated the expression of two negative regulators
      of the cell cycle, the retinoblastoma gene product (pRb) and the WAF1/Cip1 gene
      product (p21), in consecutive paraffin sections from 54 gliomas (49 astrocytomas
      and 5 oligodendrogliomas) and related it to clinicopathological parameters,
      proliferative fraction, p53 expression and survival. Survival analysis was
      restricted to the group of diffuse astrocytomas (48 patients). pRb expression did
      not correlate with histological type, grade or p53 expression, while a moderately
      strong correlation existed between pRb expression and the percentages of
      proliferating cell nuclear antigen (PCNA) and MIB-1-positive cells. In 30% of
      cases we observed diminished pRb expression (i.e., a low pRb/Ki-67 ratio),
      irrespective of grade or histological type. p21 protein was elevated in 50% of
      cases, especially within the higher grades. The percentage of p21-positive cells
      was not related to histological type or grade but correlated loosely with PCNA
      and pRb expression. A p53-negative/p21-negative phenotype was characteristic of
      oligodendrogliomas and low-grade astrocytomas, whereas the p53-positive/p21
      positive, p53-positive/p21-negative and p53-negative/p21-positive phenotypes were
      almost equally distributed among high-grade tumors. In survival analysis (either
      univariate or multivariate) diminished pRb expression was not a statistically
      significant prognostic indicator. In contrast, p21 expression emerged as an
      important indicator of shortened disease-free survival, in both univariate and
      multivariate analyses. Moreover, the double-positive p53/p21 phenotype tended to
      be associated with a shorter overall survival. Our results suggest that Rb gene
      deregulation does not significantly affect prognosis but p21 expression may play
      an important role in disease-free survival of astrocytoma patients.

PMID- 9650755
TI  - Axonal injury and the neuropathology of shaken baby syndrome.
AB  - We examined an autopsy series of 14 children with shaken baby syndrome (SBS) who
      lacked skull fracture. Evidence of axonal injury was sought using
      immunohistochemical stains for neurofilament, 68-kDa neurofilament and beta
      amyloid precursor protein (betaAPP). BetaAPP-positive axons were present in the
      cerebral white matter of all cases of SBS but were also present in 6 of 7
      children dying of non-traumatic hypoxic ischemic encephalopathy (HIE). Swollen
      axons were present in 11 of 14 cases of SBS and in 6 of 7 cases of HIE. BetaAPP
      positive axons were present in both groups in the midbrain and medulla. The
      cervical spinal cord in SBS contained betaAPP-positive axons in 7 of 11 cases; 5
      of 7 contained swollen axons within the white matter tracts; in 2
      immunoreactivity was localized to spinal nerve roots; in all 7 there was a
      predilection for staining at the glial head of the nerve root. Among cases of
      HIE, none showed abnormal axons or betaAPP-positive reactivity in the cervical
      cord white matter. We conclude that cerebral axonal injury is common in SBS, and
      may be due in part to hypoxic/ischemic injury. Cervical cord injury is also
      common, and cannot be attributed to HIE. These findings corroborate suggestions
      that flexion-extension injury about the cervical spinal column may be important
      in the pathogenesis of SBS.

PMID- 9650756
TI  - Structural and functional changes in skeletal muscle in anorexia nervosa.
AB  - Protein-energy malnutrition in anorexia nervosa is an under-recognised cause of
      muscle dysfunction. To characterise the skeletal myopathy that occurs in patients
      with severe anorexia nervosa, muscle function and structure were comprehensively
      examined in eight young adult female patients with severe (40%) self-induced
      weight loss. All of the patients showed impaired muscle function on strength and
      exercise measurement. The maximum voluntary contraction force for the patient
      group was significantly less than predicted values. Electromyography revealed
      myopathy in five of the patients, four of whom also had electro-physiological
      evidence of neuropathy. However, muscle biopsy specimens consistently showed
      myopathic changes with severe type 2 fibre atrophy but with no evidence of
      neuropathic changes. Ultrastructurally, there was separation and segmental loss
      of myofibrils and most biopsy samples contained abundant glycogen granules; we
      have previously reported that one of the most consistent biochemical
      abnormalities in these patients is impaired ischaemic lactate responses to
      forearm exercise. The result of severe protein-energy malnutrition on the musculo
      skeletal system is a metabolic myopathy. Although the patients admitted to a
      variety of abnormal dieting behaviours, such as over-exercising and self-induced
      vomiting, no association was found between any of these and quantitative
      histological changes in the muscle biopsy samples. It is recommended that
      myopathy in anorexia nervosa be treated by instituting an appropriate refeeding
      programme.

PMID- 9650757
TI  - Tissue distribution of pathological lesions and Hu antigen expression in
      paraneoplastic sensory neuronopathy.
AB  - We investigated the distribution of lesions and Hu antigen expression in two
      autopsied cases of anti-Hu antibody-positive paraneoplastic sensory neuronopathy
      (carcinomatous subacute sensory neuropathy). Pathological changes in both
      patients were limited to the primary sensory neurons, some of the sympathetic
      ganglia and hippocampal regions. The lesions showed a multifocal distribution
      that differed among the spinal segmental levels and in the individual dorsal root
      ganglia as well as in the nerve fascicles. Western blot analysis of the patients'
      serum revealed that Hu antigens were extensively and widely expressed throughout
      the central nervous system, sensory and sympathetic ganglia and cancer cells, but
      not in the non-neural visceral tissues. Reverse transcriptase-polymerase chain
      reaction also showed that the Hu D, Hu C, Hel-N1 and Hel-N2 mRNAs were
      extensively and widely expressed through the neural tissues and cancer cells, but
      not in the visceral tissues. Thus, the distribution of antigen expression was
      very different from that of the lesions. Taken together with the distribution of
      lesions and Hu antigen expression, it is suggested that factors other than anti
      Hu antibodies are also involved in the pathogenesis of this neuronopathy.

PMID- 9650758
TI  - Mixed dysembryoplastic neuroepithelial tumor and ganglioglioma.
AB  - We report a case of a 15-year-old girl with new onset seizures, who had a mixed
      dysembryoplastic neuroepithelial tumor (DNT) and ganglioglioma of the right
      parieto-occipital lobe. The tumor appeared well demarcated and exhibited a low T1
      and a high T2 signal on magnetic resonance imaging. Architecturally it was in
      large part intracortical and multinodular, but also featured a leptomeningeal
      component. The former corresponded to DNT, a proliferation of oligodendroglia
      like cells (OLCs) arranged in nodules, as well as comprising a diffuse
      internodular element featuring "floating neurons" in a mucoid matrix. The
      leptomeningeal portion of the lesion was a ganglioglioma consisting of large
      neurons and astrocytes in association with marked desmoplasia. Spatially, the two
      components abutted one another but appeared distinct. Immunohistochemistry showed
      the neurons of the ganglioglioma to be positive for class III beta-tubulin,
      synaptophysin, and chromogranin A, whereas the astrocytic cells stained only for
      glial fibrillary acidic protein. Most OLCs in the DNT were positive for S-100
      protein. This apparently mixed lesion suggests that a close histogenetic
      relationship exists between DNT and ganglioglioma. We postulate that the
      pluripotential progenitor cells residing in the subpial granular layer may have
      given rise to the cortical DNT and to the leptomeningeal ganglioglioma. To our
      knowledge, this is the first detailed histological, immunochemical and
      ultrastructural report of a mixed DNT and ganglioglioma.

PMID- 9650759
TI  - The fatal attraction of polyglutamine-containing proteins.

PMID- 9650760
TI  - Detection and incidence of cryptic Y chromosome sequences in Turner syndrome
      patients.
AB  - The presence of Y chromosome sequences in Turner syndrome (TS) patients may
      predispose them to gonadoblastoma formation with an estimated risk of 15-25%. The
      aim of this study was to determine the presence and the incidence of cryptic Y
      chromosome material in the genome of TS patients. The methodology involved a
      combination of polymerase chain reaction (PCR) and nested PCR followed by
      Southern blot analysis of three genes the sex determining region Y (SRY), testis
      specific protein Y encoded (TSPY) and RNA binding motif protein (RBM) (previously
      designated as YRRM) and nine additional STSs spanning all seven intervals of the
      Y chromosome. The methodology has a high sensitivity as it detects one 46,XY cell
      among 10(5) 46,XX cells. Reliability was ensured by taking several precautions to
      avoid false positive results. We report the results of screening 50 TS patients
      and the identification of cryptic Y chromosome material in 12 (24%) of them.
      Karyotypes were divided in four groups: 5 (23.8%) patients out of the 21 TS
      patients which have the 45,X karyotype (group A) also have cryptic Y sequences;
      none (0%) of the 7 patients who have karyotypes with anomalies on one of the X
      chromosomes have Y mosaicism (group B); 1 (6.3%) of the 16 patients with a mosaic
      karyotype have Y material (group C); and 6 (100%) out of 6 patients with a
      supernumerary marker chromosome (SMC) have Y chromosome sequences (group D). Nine
      of the 12 patients positive for cryptic Y material were recalled for a repeat
      study. Following new DNA extraction, molecular analysis was repeated and, in
      conjunction with fluorescent in situ hybridization (FISH) analysis using the Y
      centromeric specific probe Yc-2, confirmed the initial positive DNA findings.
      This study used a reliable and sensitive methodology to identify the presence of
      Y chromosome material in TS patients thus providing not only a better estimate of
      a patient's risk in developing either gonadoblastoma or another form of gonadal
      tumor but also the overall incidence of cryptic Y mosaicism.

PMID- 9650761
TI  - Sex ratio and absence of uniparental disomy in spontaneous abortions with a
      normal karyotype.
AB  - A series of spontaneous abortions collected in the South Wales region over a
      period of 18 months was karyotyped to identify those with a normal chromosome
      complement. Microsatellite polymorphisms distributed throughout all autosomes
      were typed by the polymerase chain reaction to determine the parental origin of
      each autosome pair in karyotypically normal spontaneous abortions. In 35 cases
      biparental inheritance of every autosome pair was demonstrated. The sex ratio of
      the normal spontaneous abortions of proven biparental origin was 0.77, but this
      was not significantly different from 1.00.

PMID- 9650762
TI  - G2 repair in Nijmegen breakage syndrome: G2 duration and effect of caffeine and
      cycloheximide in control and X-ray irradiated lymphocytes.
AB  - Lymphocytes from a patient with the Nijmegen breakage syndrome (NBS/NBS) and his
      parents (NBS/+) have been analyzed to identify possible disturbances in
      chromosomal G2 repair. The study included the determination of G2 duration and
      the analysis of the chromosomal aberration frequencies in lymphocytes
      with/without caffeine and cyclohexemide (CHM) treatments during G2, under control
      and X-irradiated conditions. Under control conditions, NBS/NBS lymphocytes showed
      that the basal chromosomal damage as well as the damage detected in G2, with
      caffeine treatment, and the G2 duration were higher than cells from an age
      matched control. In X-irradiated NBS/NBS lymphocytes, the basal and G2 chromosome
      aberration frequencies were higher than in the controls; however, no significant
      differences in G2 duration were detected between these two type of cells. Under X
      irradiated conditions, NBS/+ lymphocytes showed that while the level of
      chromosomal damage in G2 and the duration of this cell cycle phase were similar
      to the control cells, the frequency of unrepaired chromosomal lesions was higher
      than in the control lymphocytes. No significant differences in chromosomal damage
      and G2 duration were detected in NBS/+ lymphocytes compared to the control cells,
      under control conditions. CHM treatment, which induces an increase in G2
      duration, decreased the basal spontaneous and X-ray induced chromosome aberration
      frequency in NBS/NBS and NBS/+ lymphocytes. These results suggest that NBS
      lymphocytes might be affected by some disturbances in their ability to extend the
      G2 duration, which may be influencing their DNA repair efficiency in this phase
      of the cell cycle.

PMID- 9650764
TI  - Discordant repeat size and phenotype in Kennedy syndrome.
AB  - Previous reports in the literature have described correlation of increasing
      repeat length with severity of the phenotype, in Kennedy syndrome. We describe
      male siblings with different repeat lengths, with lack of expression of the
      phenotype in the sibling with the longer repeat length. The phenotype was
      identical to motor neurone disease. There is variability of expression in Kennedy
      syndrome and repeat length even in siblings cannot be taken as a conclusive
      indicator of severity. CAG repeat length cannot be used to predict the natural
      history of Kennedy disease. The diagnosis of Kennedy syndrome should be
      considered in male patients presenting with atypical motor neurone disease.

PMID- 9650763
TI  - Photoanthropometric study of craniofacial traits in individuals with Prader-Willi
      syndrome on short-term growth hormone therapy.
AB  - An objective photoanthropometric method, useful for delineating craniofacial
      characteristics, was performed on 20 individuals with Prader-Willi syndrome (PWS;
      14 males and 6 females) under 12 years of age and on growth hormone therapy (e.g.
      for 3-12 months) to determine the effects of therapy on craniofacial features in
      PWS. Facial parameters were measured from strict frontal and profile photographic
      35 mm slides and compared with other facial measurements from the same face (e.g.
      palpebral fissure width to bizygomatic diameter). We studied 16
      photoanthropometric craniofacial indices following previously established
      protocols. Our photoanthropometric data on 20 PWS subjects meeting diagnostic
      criteria further supported previous findings of a high midface, a broad interalar
      distance, a prominent high chin and broad ears in PWS patients without growth
      hormone therapy. In addition, while on growth hormone therapy, the high midface,
      broad interalar distance and prominent high chin appeared to accentuate over time
      in relationship to untreated PWS patients. Conversely, broad appearing ears were
      not accentuated by growth hormone therapy in the PWS subjects analyzed in this
      study.

PMID- 9650765
TI  - Wilms' tumor and gonadal dysgenesis in a child with the 2q37.1 deletion syndrome.
AB  - Here we report Wilms' tumor, gonadal dysgenesis and a bifid uterus in an 18-month
      old female with a terminal deletion of the long arm of chromosome 2
      [46,XX,del(2)(q37.1)]. Since Wilms' tumor has been previously reported in the
      2q37 deletion syndrome, the present observation raises the question of whether a
      tumor susceptibility gene maps to chromosome 2q37 and suggests giving
      consideration to the possible occurrence of Wilms' tumor in the course of
      disease.

PMID- 9650766
TI  - A novel mutation of the beta-glucocerebrosidase gene associated with neurologic
      manifestations in three sibs.
AB  - We report on a sibship in which three members were affected by Gaucher disease.
      Molecular analysis of the patients showed homozygosity for a novel mutation
      (C5390G) of the beta-glucocerebrosidase gene, resulting in the substitution of
      the arginine 353 with a glycine. Western blot analysis showed a reduced amount of
      beta-glucocerebrosidase-related polypeptides in fibroblasts. The phenotype
      resulting from this mutation is characterized by visceral and skeletal
      manifestations. In addition, the presence of seizures and electrophysiological
      abnormalities only in the 3 patients and in none of the other unaffected sibs
      suggests that the mutation is responsible for neurologic involvement.

PMID- 9650767
TI  - Prenatal diagnosis of low level trisomy 15 mosaicism: review of the literature.
AB  - Low level chromosome mosaicism found at amniocentesis is problematic for
      clinicians and patients. We report prenatal diagnosis of a fetus with a rare
      karyotype of 47,XX, + 15/46,XX. Second trimester amniocentesis was performed for
      advanced maternal age. Fetal ultrasound revealed a hypoplastic right ventricle
      and intrauterine growth retardation (IUGR). The rest of the fetal anatomy was
      within normal limits. A mosaic karyotype of 47,XX, + 15/46,XX was observed. The
      couple interrupted the pregnancy at 19 weeks by dilation and suction evacuation.
      Careful evaluation of multiple pieces of fetal parts and placenta revealed one
      abnormal finding: a single umbilical artery. Cytogenetic metaphase and
      fluorescent in situ hybridization (FISH) interphase analyses of cells from fetal
      lung, heart, placenta, and skin revealed the presence of the trisomic line in all
      tissues. Molecular analysis demonstrated that the origin of the extra chromosome
      15 was maternal, the error most likely occurred in meiosis I and the diploid line
      was of biparental inheritance. This case report discusses the associated findings
      in this fetus and reviews the literature describing other cases of mosaic trisomy
      15.

PMID- 9650768
TI  - Molecular and cytogenetic [correction of cytogenate] analysis of an X/autosomal
      translocation: 45,X,dic(X;17)(p22.2;p13)
AB  - We present an unusual case of monosomy 17p13-pter and monosomy Xp22.2-pter due to
      a dicentric translocation chromosome X/17 in a female newborn with severe
      anomalies. The karyotype was identified as 45,X,dic(X;17)(p22.2;p13) by high
      resolution GTG banding in lymphocytes. R banding showed the translocational X
      chromosome to be late replicating, and there was no spreading of X-inactivation
      onto the autosomal segment. Furthermore, it could be demonstrated by C banding
      that the X-centromere in the translocation chromosome was inactive. The results
      of short tandem repeat (STR) typing confirmed the partial monosomy X and 17 as
      well as the paternal origin of the two chromosomes X and 17 which were involved
      in the translocation chromosome formation. The cell stage of the structural
      rearrangement was consistent with paternal meiosis as well as with postzygotic
      mitosis. The monosomy was confirmed in lymphocytes and fibroblasts, and mosaicism
      was not detected.

PMID- 9650769
TI  - Complex chromosomal rearrangements associated with congenital erythrophagocytotic
      histiocytosis.
AB  - We describe a patient with a congenital malignant blood disorder and a
      constitutional de novo chromosomal rearrangement that includes four breakpoints.
      By conventional cytogenetic analysis an obviously reciprocal balanced
      translocation with the breakpoints 1p36 and 5q11.2 was diagnosed. Due to a
      suspicious dark band in the breakpoint area of 1p a more detailed analysis of the
      breakpoints was performed using microdissection and reverse chromosome painting.
      This revealed a small inversion at 1p36 that must have occurred prior to the
      reciprocal translocation. The three breakpoints in chromosome 1 (1p36.11, 1p36.21
      and 1p36.31) are within or close by regions known to contain tumor suppressor
      genes. The chromosomal rearrangement might have resulted either in a
      submicroscopic deletion, in loss of heterozygosity of one or more imprinted
      genes, or in gene position effects as possible explanations for the clinical
      course of our patient.

PMID- 9650770
TI  - Apparent normalisation of fetal renal size in autosomal dominant polycystic
      kidney disease (PKD1).
AB  - We present a family with adult onset autosomal dominant polycystic kidney disease
      (ADPKD) in two generations, linked to the PKD1 locus and with paternal
      transmission to the fetus. The fetus carried the PKD1 haplotype and was,
      therefore a gene carrier. Progressive hyperechogenic renal enlargement, but no
      cysts, was documented by serial fetal ultrasounds at 21, 23 and 34 weeks of
      gestation. Surprisingly, the newborn renal scan showed normal sized kidneys with
      apparently normal corticomedullary differentiation. However, at 11 months of age,
      the evolution of cysts in one kidney, and then in the other kidney at 20 months,
      was documented by ultrasound in the absence of clinical symptoms or signs. The
      observed normalisation of fetal renal ultrasound appearances at birth has not
      previously been described in fetuses presenting with PKD1.

PMID- 9650771
TI  - Kabuki (Niikawa-Kuroki) syndrome associated with immunodeficiency.
AB  - We report a case of a 19-year-old male with the cardinal features of the Kabuki
      syndrome (KS) and, in addition, with severe immunodeficiency. Finding immune
      deficiency in a KS patient, prompted us to determine whether this association was
      related to a deletion within the DiGeorge chromosomal region. Fluorescence in
      situ hybridization (FISH) with the Oncor probe N25(D22S75) revealed no deletion
      of 22q11.2 in the patient.

PMID- 9650772
TI  - Tetranucleotide repeat polymorphism at the CCSP gene.

PMID- 9650773
TI  - A novel Mbo II polymorphism in exon 15 of the human adenomatous polyposis coli
      gene.

PMID- 9650774
TI  - Cerebral aqueductal stenosis as a presentation of deletion 6q25-qter.

PMID- 9650775
TI  - Two cases of prenatally diagnosed diaphragmatic hernia accompanied by the same
      undescribed chromosomal deletion (15q24 de novo)

PMID- 9650776
TI  - Apolipoprotein E alleles in mothers of trisomy 18 conceptuses.

PMID- 9650777
TI  - An alpha-actinin-profilin chimaera with two alternatively operating actin-binding
      sites.
AB  - Studying the mode of interaction between actin and actin-binding proteins, we
      constructed a chimaeric protein consisting of the sequence for bovine profilin I
      (P), to which the sequence for the actin-binding domain of Dictyostelium
      discoideum alpha-actinin (alphaA1-2) was fused N-terminally. The resulting hybrid
      clone was expressed in Escherichia coli, and the chimaeric protein, alphaA1-2P,
      purified by affinity chromatography on poly-(L-proline) (PLP) columns and
      identified using specific antibodies. High resolution electron microscopy
      demonstrated that this protein consists of two discrete subdomains. In
      biochemical, viscometric and electron microscopic analyses, we showed that both
      modules in this molecule are biologically active. The chimaera binds to poly-(L
      proline) and inhibits the polymerization of G-actin in KCl, which is consistent
      with the assumption that the profilin part is intact. Inhibition of actin
      polymerization in KCl was stronger than that of the parental profilin, and the Kd
      value of its interaction with rabbit skeletal muscle actin, as determined by
      falling ball viscometry, was smaller (mean value 0.5 x 10(-6) M, as compared to
      1.9 x 10(-6) M for bovine profilin). In 2mM MgCl2, the actin polymerized rapidly,
      consistent with the interpretation that under these conditions the chimaera, like
      profilin, is less efficient as an actin-sequestering agent. In the presence of
      alphaA1-2P, the resulting filaments were decorated with particles projecting from
      the filament axis. We conclude that under these conditions the alphaA1-2 domain
      of alphaA1-2P is preferentially active, attaching the chimaeric particles
      laterally to the filaments. Hence, the parental modules combined in alphaA1-2P
      permit this molecule to switch from a G-actin- to an F-actin-binding form.

PMID- 9650778
TI  - Actin microfilaments are essential for the cytological positioning and morphology
      of the Golgi complex.
AB  - The organization and function of the Golgi complex was studied in normal rat
      kidney cells following disruption of the actin cytoskeleton induced by
      cytochalasin D. In cells treated with these reagents, the reticular and
      perinuclear Golgi morphology acquired a cluster shape restricted to the
      centrosome region. Golgi complex alteration affected all Golgi subcompartments as
      revealed by double fluorescence staining with antibodies to the cis/middle
      Mannosidase II and the trans-Golgi network TGN38 proteins or vital staining with
      the lipid derivate C6-NBD-ceramide. The ultrastructural and stereological
      analysis showed that the Golgi cisternae remained attached in a stacked
      conformation, but they were swollen and contained electron-dense intra-cisternal
      bodies. The Golgi complex cluster remained linked to microtubules since it was
      fragmented and dispersed after treatment with nocodazole. Moreover, the
      reassembly of Golgi fragments after the disruption of the microtubuli with
      nocodazole does not utilize the actin microfilaments. The actin microfilament
      requirement for the disassembly and reassembly of the Golgi complex and for the
      ER-Golgi vesicular transport were also studied. The results show that actin
      microfilaments are not needed for either the retrograde fusion of the Golgi
      complex with the endoplasmic reticulum promoted by brefeldin A or the anterograde
      reassembly after the removal of the drug, or the ER-Golgi transport of VSV-G
      glycoprotein. However, actin microfilaments are directly involved in the
      subcellular localization and the morphology of the Golgi complex.

PMID- 9650779
TI  - Quantitative immunoelectron microscopy reveals alpha2,6 sialyltransferase is
      concentrated in the central cisternae of rat hepatocyte Golgi apparatus.
AB  - The Golgi apparatus is a membrane bound organelle involved in synthesis of N
      linked oligosaccharides which are trimmed and then lengthened by a series of
      sugar transferases adding N-acetylglucosamine, galactose and sialic acid in
      sequence. We previously published qualitative work which localized
      Galbeta1,4GlcNAc alpha2,6 sialyltransferase of rat hepatocytes to the trans
      cisternae and the trans Golgi network. We now report the use of combined
      stereological and immunoelectron microscopical techniques for mapping the Golgi
      stack composition and distribution of sialyltransferase protein in rat
      hepatocytes. The Golgi stack showed substantial variation in composition
      consisting of 1, 2, 3, 4, or 5 cisternae with an average of 2.5 cisternae.
      Sialyltransferase labeling was mainly located in the central cisternae of the
      Golgi stacks irrespective of whether the stacks were oriented in a cis/trans
      direction using morphological criteria. Only 20% of the total sialyltransferase
      labeling was present in the transmost cisterna and 2% in the trans Golgi Network.
      The low labeling in the transmost cisterna was essentially due to the presence of
      a sialyltransferase negative cisterna. These data emphasize the importance of
      quantitation in obtaining a representative picture of Golgi enzyme distribution
      in three dimensions. They indicate that central cisternae, rather than the
      transmost cisterna and TGN, function in sialylation along the secretory pathway
      of rat hepatocytes.

PMID- 9650780
TI  - The leucine-based motif DDQxxLI is recognized both for internalization and
      basolateral sorting of invariant chain in MDCK cells.
AB  - The major histocompatibility complex (MHC) class II-associated invariant chain
      (Ii) contains signals for transport to endocytic compartments where the class II
      molecules bind antigenic peptides for presentation to CD4+ T cells. Two leucine
      based signals in the Ii cytoplasmic tail can be independently recognized for
      endosomal sorting of Ii, and we have recently shown that each signal is
      sufficient for basolateral sorting and internalization of Ii in polarized Madine
      Darby Canine Kidney (MDCK) II cells. The recognition motif for endosomal sorting
      is complex and consists of two critical leucine-like residues as well as
      surrounding amino acids. Here, we have analyzed the importance of residues
      surrounding the membrane-distal leucine-based signal in basolateral sorting and
      internalization of Ii in MDCK II cells. We find that the DDQxxLI motif is
      involved in both sorting events indicating the presence of similar signal
      recognition components both at the TGN and at the plasma membrane. The identical
      motif is required for endosomal localization and internalization of Ii also in
      simian COS cells and the human HeLa and M1 cells.

PMID- 9650781
TI  - Tyrphostin A9 and wortmannin perturb the Golgi complex and block proliferation of
      vascular smooth muscle cells.
AB  - To proliferate, vascular smooth muscle cells first convert from a contractile to
      a synthetic phenotype. Earlier studies indicate that this process is supported by
      fibronectin and accelerated by platelet-derived growth factor (PDGF). Here, the
      mechanisms in this transition were further explored. Isolated rat aortic smooth
      muscle cells were treated with tyrphostin A9, a PDGF receptor tyrosine kinase
      inhibitor, and wortmannin, a phosphoinositide 3-kinase inhibitor. Electron
      microscopy did not show any effect on the reorganization of the cells during the
      first days in culture, i.e. the loss of actin filaments and the formation of a
      large secretory apparatus. Conversely, both drugs caused hypertrophy of the Golgi
      complex, with large and partly vacuolized cisternal stacks. Nevertheless, a
      juxtanuclear staining pattern for the Golgi enzyme mannosidase II, the coat
      protein beta-COP, and the PDGF beta-receptor was retained. Moreover, the serum
      induced proliferation of the cells was blocked. These findings suggest that
      signaling via PDGF receptor tyrosine kinases and phosphoinositide 3-kinases is
      not necessary for the shift of the smooth muscle cells from a contractile to a
      synthetic phenotype. On the other hand, these enzymes apparently carry out
      important functions in the control of intracellular membrane traffic and cell
      division.

PMID- 9650782
TI  - Traffic into the prevacuolar/endosomal compartment of Saccharomyces cerevisiae: a
      VPS45-dependent intracellular route and a VPS45-independent, endocytic route.
AB  - The vps (vacuolar protein sorting) mutants have been used to dissect and
      characterize the vacuolar biogenesis pathway in the yeast Saccharomyces
      cerevisiae. The vps mutants were isolated through their loss of ability to
      correctly sort the vacuolar hydrolase CPY, which travels from Golgi membranes to
      the vacuole through a prevacuolar compartment. Over 50 VPS genes have been
      divided into 6 classes according to vacuolar morphology. Mutations in any one of
      the class E VPS genes, such as VPS27, lead to an exaggerated form of the
      prevacuolar compartment. This class E compartment contains endocytosed proteins
      as well as proteins en route to the vacuole, and is thus taken to represent an
      intersection point between the endocytic and biosynthetic pathways. Mutations in
      the class D gene VPS45 can be used to define a second transport intermediate
      along the vacuolar biogenesis pathway, Golgi-derived transport vesicles carrying
      vacuolar membrane proteins on their way to the vacuole. Here we demonstrate that
      the Sec1p-like protein Vps45p is required for the fusion of Golgi-derived
      vesicles with the prevacuolar compartment indicating that VPS45 functions before
      VPS27 in the vacuolar biogenesis pathway. In addition, we show that VPS45
      function is not required for the delivery of endocytosed proteins to the
      prevacuolar compartment from the plasma membrane suggesting that the function of
      Vps45p is restricted to a single vesicular pathway.

PMID- 9650783
TI  - Iodination of mature cathepsin D in thyrocytes as an indicator for its transport
      to the cell surface.
AB  - Thyrocytes are known for their ability to iodinate thyroglobulin from which the
      thyroid hormones are generated. In the intact thyroid gland the iodination
      process is almost exclusively executed at the apical plasma membrane of thyroid
      epithelial cells. Here, we show that freshly isolated thyrocytes iodinated
      polypeptides other than thyroglobulin and that one of the major iodinated
      polypeptides was the mature form of the lysosomal protease cathepsin D (CD). The
      detection of mature CD as an iodinated polypeptide suggested that a fraction of
      the lysosomally maturated enzyme was delivered to the apical plasma membrane
      where it became available for iodination. After labeling of thyrocytes with
      [35S]methionine/cysteine overnight part of the mature CD was released into the
      culture medium. This was abolished by inhibiting maturation of CD with NH4Cl,
      indicating that mature CD appeared in the medium after its proteolytic maturation
      in an acidic compartment. Besides CD other soluble lysosomal polypeptides like
      the beta-N-acetylhexosaminidase and the sphingolipid-activating protein D (Sap D)
      were iodinated and partially secreted as mature polypeptides. In contrast, the
      membrane-associated lysosomal ceramidase was iodinated and partially secreted as
      immature single-chain enzyme and not as fully maturated two-chain enzyme. These
      data indicate that a portion of mature CD and other soluble lysosomal enzymes is
      delivered from lysosomes to the cell surface whereas some membrane-associated
      enzymes from the terminal lysosomal compartment are efficiently excluded from
      this process.

PMID- 9650784
TI  - Cell fate specification in an in vitro model of neural development.
AB  - We have studied in an in vitro model of neural development the effect of
      neighboring cells on the fate of single fluorescently labeled precursor cells. In
      one line of experiments, PCC7-Mz1 embryonal carcinoma cells were transiently
      transfected with "green fluorescent protein" (GFP) and, following incubation with
      0.1 microM all-trans retinoic acid (RA), the number and morphology of derivatives
      (neuronal or non-neuronal) was determined that form groups of GFP-expressing
      cells in a surrounding of unlabeled cells. Because single PCC7-Mz1 cells can
      produce single-lineage and mixed-lineage derivatives, they are individually
      pluripotent. In another line of experiments, we have analyzed the fate of GFP
      expressing PCC7-MzN cells in different cellular environments. Whereas in the
      absence of other cells, PCC7-MzN cells exclusively differentiated to neuronal
      derivatives following RA induction (Lang, E., M. L. Mazauric-Stuker, A. Maelicke,
      J. Cell Biol. 109, 2481-2493 (1989)), they differentiated also to non-neuronal
      phenotypes (astrocytes and fibroblasts) when co-cultured with either PCC7-Mz1
      stem cells or freshly RA-induced cells. The fate of PCC7-MzN cells could also be
      shifted in the absence of other cells when the cells were grown on laminin-coated
      surfaces. These results suggest that a putative fate-shifting activity (FSA) is
      released by PCC7-Mz1 and PCC7-MzN cells which requires, at least in the case of
      MzN cells, presentation by extracellular matrix-like structures in order to
      function in cell fate specification. Very few other cell types, in particular
      primary cultures of mouse forebrain cells of embryonic day 13, were capable of
      shifting the developmental potential of PCC7-MzN cells in a similar manner as
      PCC7-Mz1 cells do. We conclude that cell type specification in this model of
      neural development may occur by similar mechanisms as have been established in
      Drosophila neurogenesis. A default pathway (neuronal) is modulated by lateral
      signaling between neighboring cells so that cellular diversity can arise from
      initially homogeneous populations of progenitor cells.

PMID- 9650785
TI  - Surface exposure of phosphatidylserine during apoptosis of rat thymocytes
      precedes nuclear changes.
AB  - Cell surface exposure of phosphatidylserine (PS) during apoptosis serves
      recognition and removal of the dying cell by phagocytes. Loss of phospholipid
      asymmetry and PS exposure is investigated by immunocytochemistry and related to
      morphological changes. Loss of membrane asymmetry was determined on dexamethasone
      treated rat thymocytes using the PS specific probe annexin V. Thymocytes
      incubated in the presence of dexamethasone were studied in time series during the
      execution of the apoptotic program. Thymocytes first start to expose PS at their
      cell surface. At this initial stage the barrier function of the plasma membrane
      remains intact. At a later stage the plasma membrane becomes leaky for compounds
      like propidium iodide and subsequently the cell disintegrates into apoptotic
      bodies. Microscopical evaluation of dexamethasone-treated thymocytes showed that
      the cells with an apoptotic morphology all bound annexin V. The cells with a
      normal viable morphology lacked annexin V binding except for those cells that
      started to shed small vesicles. These vesicles were positive for annexin V,
      indicating a local disturbance of the phospholipid asymmetry. The local exposure
      of PS is considered to be a very early event of apoptosis, preceding the full
      sequence of morphological changes at the ultrastructural level.

PMID- 9650786
TI  - Optical pumping in indium phosphide: 31P NMR measurements and potential for
      signal enhancement in biological solid state NMR.
AB  - The initial results of optically-pumped, directly-detected NMR experiments on InP
      are reported. At low temperatures (4.2 K and above) and in a 9.39 T magnetic
      field, irradiation of a sample of an undoped InP wafer with 835-nm-wavelength
      light from a diode laser enhances the spin polarization of 31P nuclei near the
      sample surface in a manner that depends on the polarization of the light. The
      nuclear spin polarization is monitored by direct radio-frequency detection of
      nuclear free induction-decay signals. The maximum nuclear spin polarization (Szn>
      generated by optical pumping is approximately - 0.004, corresponding to a spin
      temperature of -0.5 K. The nuclear spin polarization may be limited in these
      experiments by the use of a high photon energy (1.484 eV) relative to the InP
      band gap (1.423 eV at low temperatures). It is proposed that optically-pumped InP
      may be useful as a source of enhanced nuclear spin polarizations for solid state
      NMR measurements on organic and biological overlayers deposited on InP
      substrates. Estimates are given for the magnitude of the spin polarization and
      the efficiency of the polarization transfer from the semiconductor substrate to
      the overlayer that would be required to permit solid state NMR measurements on
      sub-nanomole quantities of molecules in the overlayer. These estimates appear
      well within the range of possibility.

PMID- 9650787
TI  - Microscopic interpretation of optically pumped NMR signals in GaAs.
AB  - By numerical modelling and least squares fitting to the field, time and
      polarization dependence of optically pumped 69Ga NMR data in semi-insulating GaAs
      at low temperature and high field, a microscopic picture of this phenomenon
      emerges. Numerical values can be obtained for the key optical pumping parameters:
      the correlation time for the electron-nuclear contact interaction, and the
      electronic g-factor. The values of these parameters, which are in close agreement
      with previously reported values, can be combined with literature estimates for
      the average hyperfine interaction and spin diffusion coefficient D to generate
      numerical solutions for the Zeeman nuclear spin order, <Iz>(r,t). The modelling
      permits the influence of variations with any other relevant parameter to be
      predicted. Experimentally, the optical polarization and time dependence data are
      presented. Least squares fits to the optical polarization dependence yield a
      value for the optically induced electron spin polarization at the given field,
      temperature, and excitation intensity. With the numerical solutions <Iz>(r,t)
      that best fit the available data, the hyperfine frequency shift can be used to
      simulate the time evolution of the 69Ga NMR line shape. These simulations provide
      guidance on how to optimize the experimental conditions to most effectively
      observe hyperfine effects near shallow donors in this particular material.

PMID- 9650788
TI  - Solid state NMR studies of photoinduced polarization in photosynthetic reaction
      centers: mechanism and simulations.
AB  - We simulate Photo-Chemically Induced Dynamic Nuclear Polarization in the 15N
      solid-state NMR of 15N-labeled photosynthetic reaction centers using a Radical
      Pair Mechanism (RPM). According to the experimental data, the directly polarized
      nuclei include all eight nitrogens in the ground state of the bacteriochlorophyll
      special pair (P), and N-II in the bacteriopheophytin acceptor (H) [M.G.
      Zysmilich, A.E. McDermott, J. Am. Chem. Soc., 116 (1994) 8362-8363.] [M.G.
      Zysmilich, A. McDermott, J. Am. Chem. Soc., 118 (1996) 5867-5873.] [M.G.
      Zysmilich, A. McDermott, Proc. Natl. Acad. Sci. U.S.A., 93 (1996) 6857-6860.];
      other signals are polarized in nonspecifically labeled samples, but the
      polarization apparently results from magnetization exchange with neighboring
      polarized nitrogens, and these are not treated in this work. Two quantitative
      models for the polarization associated with the RPM are presented and are used to
      test the validity of the proposal that this mechanism is cooperative in the
      reaction centers. The kinetic models can treat the steady state polarizations as
      well as the approach to steady state, and in principle could be expanded to
      include anisotropic effects, or pulse-probe experiments. Several features of the
      detailed simulations of the steady-state amplitudes and the kinetics of the
      approach to steady-state are compared with our data, including the signs and
      approximate absolute magnitudes of the polarization on the nitrogen nuclei in P
      and H(L), and the changes in the relative amplitudes with the change in the
      lifetime of the molecular triplet, photoaccumulation time, nuclear relaxation
      rate and illumination intensity. The simulations demonstrate that the
      polarization intensities are in qualitative agreement with those predicted for
      the RPM, including the curious observation of strong polariza-tion on the
      pheophytin acceptor for certain experimental conditions. However, this agreement
      requires efficient relaxation of the nitrogens on H(L) by 3P, due to a fortuitous
      low nanosecond value for the spin-lattice relaxation for the electrons in the
      molecular triplet of the donor, T1e of 3P. Whether this fortuitous match is valid
      is unproven.

PMID- 9650789
TI  - Optical NMR from single quantum dots.
AB  - Nuclear magnetic resonance (NMR) from constituent Ga and As nuclei was optically
      detected on excitonic recombination in single GaAs quantum dots formed by
      interface fluctuations in GaAs/Al0.3Ga0.7As quantum wells. Orientation of the
      nuclear spin system by optical pumping causes an Overhauser shift of the
      excitonic energy levels proportional to the degree of nuclear orientation. NMR
      was subsequently detected by monitoring changes in the combined Overhauser plus
      Zeeman splitting of excitons localized in single quantum dots as the RF frequency
      was swept through a nuclear resonance. The NMR signals originate from
      approximately 10(5) nuclei in the quantum dot-with dimensions of approximately 4
      nm X 10 nm X 100 nm--illustrating the extreme sensitivity and spatial resolution
      of the technique. NMR from such small structures provides a chemically specific
      probe of the local environment on the nanometer scale.

PMID- 9650790
TI  - Projection noise in the optically detected magnetic resonance signal of a single
      electron spin.
AB  - The spin quantum noise owing to a single molecular triplet electron spin jumping
      from one eigenstate to another has been detected. As a result of the
      superposition of two spin eigenstates in the triplet level of the molecule by a
      microwave pi/2-pulse an increase in the noise of the fluorescence intensity of a
      single molecule is detected. This increase in noise is attributed to the decay of
      coherence between the two spin eigenstates.

PMID- 9650791
TI  - Magnetic resonance force microscopy with a ferromagnetic tip mounted on the force
      detector.
AB  - The Magnetic Resonance Force Microscope (MRFM) presents the opportunity for a
      magnetic resonance imaging probe with ultra-high, potentially atomic-scale,
      resolution. The successful application of this technique in detection of nuclear
      magnetic, electron-spin and ferromagnetic resonance (FMR) highlights its
      significant potential. We discuss the capabilities of the MRFM with particular
      emphasis on the detection of FMR using MRFM techniques. A crucial remaining
      challenge in the development of the magnetic resonance force microscope (MRFM) is
      to place the magnetic probe on the mechanical resonator. We address the problem
      of spurious detector response arising from interactions between the magnetic tip
      and various external applied fields. We show that miniature, magnetically
      polarized Nd2Fe14B particles show promise as magnetic probe tips. Our experience
      indicates it will be important to minimize the total polarized moment of the
      magnetic tip and to ensure that the applied fields are as uniform as possible.

PMID- 9650792
TI  - Force-detected magnetic resonance without field gradients.
AB  - A novel method of nuclear magnetic resonance (NMR) is described which promises to
      be preferable to known general methods at sample length scales below
      approximately 100 microm. Its advantages stem from the seemingly paradoxical
      combination of a homogeneous static magnetic field and detection of a mechanical
      force between a spin-bearing sample and a magnet assembly. In contrast to other
      methods of force-detected nuclear magnetic resonance (FDNMR), the method is
      characterized by better observation of magnetization, enhanced resolution, and no
      gradient (BOOMERANG), and it is generally applicable with respect to sample
      composition, pulse sequence, and magnetic field strength. Further advantages of
      portability and low cost stem from the small instrument volume and mass and
      promise to extend the use of NMR to new applications and environments. A
      sensitivity analysis, relevant to spectroscopy or imaging, quantifies the
      advantage of BOOMERANG relative to magnetic induction using microcoils and to
      FDNMR methods that rely on large gradients of the magnetic field at the sample.

PMID- 9650793
TI  - Particle detected Fourier transform NMR at single crystal surfaces--6Li on
      Ru(001).
AB  - Fourier transform nuclear magnetic resonance at single crystal surfaces is
      described. The adsorption of 6Li on Ru(001) is investigated by newly developed
      techniques utilizing atomic beam sample preparation and optical detection of the
      NMR signal on desorbing atoms (laser induced fluorescence) or ions (beamfoil
      spectroscopy). In complete analogy to magnetically detected NMR, the transverse
      magnetisation is coherently recorded. This allows pulse NMR to be applied to
      surface problems.

PMID- 9650794
TI  - Muon spin relaxation studies of interstitial and molecular motion.
AB  - The unusual methods of preparation and analysis of spin polarization in muSR
      spectroscopy, which exploit the unique properties of the positive muon, are
      introduced in this article. Following a summary overview of applications,
      particular attention is paid to the problem of spin-lattice relaxation for a muon
      experiencing a hyperfine interaction with a single unpaired electron. The
      specific cases considered are the interstitial diffusion of muonium--the 1
      electron atom which may be considered as a light isotope of hydrogen-and the
      molecular dynamics of organic radicals labelled by muonium. Rate equations for
      the evolution of population in the hyperfine-coupled spin states are solved
      numerically for various relaxation mechanisms. The formalism is equally valid for
      conventional ESR studies of paramagnetic states but is pursued specifically to
      simulate T1-relaxation in muSR. The simulations are compared with literature
      data. Also treated is the case of intermittent hyperfine coupling, appropriate to
      electron capture and loss in semiconductors or soliton motion in polymers; for
      this, a Monte Carlo approach is used to simulate the muon response. (For low
      dimensional motion, the relaxation function is not exponential, so that a unique
      value of T1 cannot be defined.) Finally, a proposal is made to implement muon-T1
      measurements in the rotating frame; this is designed for the selective study of
      electronically diamagnetic muonium states (i.e., those without hyperfine
      coupling) in the presence of a paramagnetic muonium or radical fraction.

PMID- 9650795
TI  - Nuclear magnetic resonance by measuring reaction yield of spin symmetry species.
AB  - It is proposed that the nuclear magnetic resonance of sites which release
      dihydrogen can be obtained by measuring the branching fraction to the ortho and
      para forms. The motivation is to transform the sensitivity problem from that of
      detecting magnetization into the more tractable one of establishing the para and
      ortho content of free H2. It is shown with a density operator formalism that the
      para mole fraction reports directly on the zero-quantum coherence of the
      precursor and that other spin operators may be observed indirectly. Spectra are
      simulated for the case of a surface site from which H2 is released.

PMID- 9650796
TI  - The excitation of NMR transitions by the current in a sample and the proposals
      for its detection.
AB  - A new magnetic resonance technique for investigating conducting samples is
      described. NMR transitions are excited by the magnetic field of alternating
      current which flows across the sample. The dissipation of the energy caused by
      NMR transitions results in a change of the impedance of the sample. The NMR
      signal is detected as an associated change of the voltage drop across a sample
      while passing through the resonance region. It is predicted that the resonance
      can be detected by state-of-the-art low-noise superconducting quantum
      interference device (SQUID)-based NMR spectrometers. The method is believed to be
      useful for investigations of small-volume samples which are inaccessible by other
      NMR techniques.

PMID- 9650797
TI  - SQUID detected NMR and NQR. Superconducting Quantum Interference Device.
AB  - The dc Superconducting QUantum Interference Device (SQUID) is a sensitive
      detector of magnetic flux, with a typical flux noise of the order 1 muphi0 Hz(
      1/2) at liquid helium temperatures. Here phi0 = h/2e is the flux quantum. In our
      NMR or NQR spectrometer, a niobium wire coil wrapped around the sample is coupled
      to a thin film superconducting coil deposited on the SQUID to form a flux
      transformer. With this untuned input circuit the SQUID measures the flux, rather
      than the rate of change of flux, and thus retains its high sensitivity down to
      arbitrarily low frequencies. This feature is exploited in a cw spectrometer that
      monitors the change in the static magnetization of a sample induced by radio
      frequency irradiation. Examples of this technique are the detection of NQR in
      27Al in sapphire and 11B in boron nitride, and a level crossing technique to
      enhance the signal of 14N in peptides. Research is now focused on a SQUID-based
      spectrometer for pulsed NQR and NMR, which has a bandwidth of 0-5 MHz. This
      spectrometer is used with spin-echo techniques to measure the NQR longitudinal
      and transverse relaxation times of 14N in NH4ClO4, 63+/-6 ms and 22+/-2 ms,
      respectively. With the aid of two-frequency pulses to excite the 359 kHz and 714
      kHz resonances in ruby simultaneously, it is possible to obtain a two-dimensional
      NQR spectrum. As a third example, the pulsed spectrometer is used to study NMR
      spectrum of 129Xe after polariza-tion with optically pumped Rb. The NMR line can
      be detected at frequencies as low as 200 Hz. At fields below about 2 mT the
      longitudinal relaxation time saturates at about 2000 s. Two recent experiments in
      other laboratories have extended these pulsed NMR techniques to higher
      temperatures and smaller samples. In the first, images were obtained of mineral
      oil floating on water at room temperature. In the second, a SQUID configured as a
      thin film gradiometer was used to detect NMR in a 50 microm particle of 195Pt at
      6 mT and 4.2 K.

PMID- 9650798
TI  - Ion-transporting ATPases as ion channels.
AB  - Ion-transporting ATPases (pumps) hydrolyze ATP to maintain ion gradients across
      cell membranes. A presupposition for the maintenance of the gradients is that the
      ionophore of the pump that conducts the ions is accessible only from one of the
      two surfaces of the plasma membrane at any given time. Thus, a characteristic
      feature of pumps is an occluded state of the transported ions, whereas ion
      channels upon stimulation remain open at both ends and allow ions to flow through
      them down their chemical gradients. Recent experiments, however, provide evidence
      that a channel, simultaneously open on both sides of the plasma membrane, can
      also be formed within the mammalian sodium pump (Na+,K+-ATPase) upon its
      interaction with the marine toxin palytoxin, thus underlining common structural
      features shared by channels and pumps. This assumption is further supported by
      the demonstration of structural and functional homology between the extracellular
      loop of the sodium pump alpha subunit connecting the M7 and M8 transmembrane
      spans and the P-loops of Na+ channels. Possibly, pumps are simply channels that
      are able to be gated by ATP and its product phosphate.

PMID- 9650799
TI  - [125I]Tyr10-cortistatin14 labels all five somatostatin receptors.
AB  - The recently cloned rat preprocortistatin, which shows homology to the
      preprosomatostatin peptide, is thought to be enzymatically cleaved to
      cortistatin14 (CST14) similarly to somatostatin14 (SRIF14). High structural
      similarity of cortistatin14 compared to SRIF14 suggested binding properties to
      somatostatin receptors similar to SRIF14. In the present study, we expressed
      stably the five human somatostatin receptor subtypes (hsst1-hsst5) in CCL39 cells
      (Chinese hamster lung fibroblast cells). The receptors were labelled with an
      iodinated analogue of CST14 ([125I]Tyr10)-cortistatin14, [125I]Tyr10-CST) to
      establish the pharmacological profile of hsst1-hsst5 sites labelled with
      [125I]Tyr10-CST. In parallel, [Leu8,D-Trp22,125I-Tyr25]-SRIF28 ([125I]LTT-SRIF28)
      was used as a control at the five recombinant SRIF receptors stably expressed in
      CCL39 cells. High affinity [125I]Tyr10-CST binding could be demonstrated to all
      five recombinant somatostatin receptor subtypes. The pKd (-log mol/l) and Bmax
      values (fmol/mg) for hsst1-5 receptors were: 10.02+/-0.04, 220+/-30; 9.45+/-0.09,
      340+/-70; 10.06+/-0.11, 340+/-50; 9.67+/-0.14, 340+/-110 and 10.33+/-0.03, 5630+/
      1330, respectively. The pharmacological profiles determined with [125I]Tyr10-CST
      and [125I]LTT-SRIF28 were very similar at every receptor studied. These data
      suggest that cortistatin and somatostatin have similar high affinity for SRIF
      receptors. None of the receptors showed marked selectivity for either CST14/CST17
      or the somatostatins. In conclusion, the data show that cortistatin and
      somatostatin have very similar high affinity to all five recombinant somatostatin
      receptors. It remains to be seen whether there are specific receptors which bind
      only somatostatins or cortistatins.

PMID- 9650800
TI  - Interaction of 5-HT1B/D ligands with recombinant h 5-HT1A receptors: intrinsic
      activity and modulation by G-protein activation state.
AB  - Many 5-HT1B/D receptor ligands have affinity for 5-HT1A receptors. In the present
      study, the intrinsic activity of a series of 5-HT1B/D ligands was investigated at
      human 5-HT1A (h 5-HT1A) receptors by measuring G-protein activation in
      recombinant C6-glial and HeLa membranes, using agonist-stimulated [35S]GTPgammaS
      binding. In these two membrane preparations, the density of h 5-HT1A receptors
      (i.e., 246 to 320 fmol mg(-1) protein) and of their G-proteins, and the receptor:
      G-protein density ratio (0.08 to 0.18) appeared to be similar. It was found that:
      (i) the maximal [35S]GTPgammaS binding responses induced by the 5-HT1B/D receptor
      ligands in the HeLa preparation at 30 microM GDP were comparable to that of the
      native agonist 5-HT; (ii) as compared to 5-HT (1.00), similar potencies but lower
      maximal responses were observed in the C6-glial preparation at 0.3 microM GDP for
      zolmitriptan (0.89), dihydroergotamine (0.81), rizatriptan (0.71), CP122638
      (0.69), naratriptan (0.60) and sumatriptan (0.53); and that (iii) maximal
      [35S]GTPgammaS binding responses induced by 5-HT1B/D ligands in the C6-glial
      preparation were either unaffected or significantly enhanced by increasing the
      GDP concentration from 0.3 to 30 microM and higher concentrations. These features
      differ from those observed with 5-HT1A receptor agonists; the latter display the
      same rank order of potency and efficacy in both membrane preparations, and
      increasing the amount of GDP with C6-glial membranes results in an attenuation of
      both the agonist's maximal effect and the apparent potency of partial agonists.
      The differential regulation of 5-HT1A and 5-HT1B/D agonist responses by GDP
      suggests that different G-protein subtypes are involved upon 5-HT1A receptor
      activation by 5-HT1A and 5-HT1B/D agonists.

PMID- 9650801
TI  - In vivo labelling of the mouse brain 5-hydroxytryptamine1A receptor with the
      novel selective antagonist 3H-NAD-299.
AB  - The in vivo labelling of 5-hydroxytryptamine (5-HT)1A receptors in the mouse
      brain was studied with the novel selective 5-HT1A receptor antagonist, NAD-299
      ((R)-3-N,N-dicyclobutylamino-8-fluoro-3,4-dihydro-2H-1-benzopyran- 5-carboxamide
      hydrogen (2R,3R)-tartrate monohydrate). 3H-NAD-299 was injected in a tail vein
      and the radioactivity in various brain regions was determined. More than 90% of
      the radioactivity in hippocampus, 15 min after the injection, was intact NAD-299.
      At this time the amount of 3H-NAD-299 was highest in hippocampus followed by
      frontal cortex, mesencephalon, hypothalamus, striatum and cerebellum. The
      specific accumulation of radioactivity (after subtracting cerebellum values) in
      frontal cortex and hippocampus was maximal 10 to 30 min after the injection and
      had almost disappeared after 2 h. Saturation kinetics derived Bmax (pmol/g wet
      weight tissue) values of 19.6+/-2.0 in frontal cortex and 38.0+/-3.5 in
      hippocampus. The apparent Kd values expressed in nmol/kg 3H-NAD-299 injected,
      were 12.3+/-2.2 in frontal cortex and 20.3+/-3.1 in hippocampus. The 5-HT1A
      receptor antagonist, WAY-100,635 competitively inhibited the specific
      accumulation of 3H-NAD-299 and was about equipotent with unlabelled NAD-299 with
      ED50 values of 20-30 nmol/kg s.c. These compounds were about 10 times more potent
      than the 5-HT1A receptor antagonists, p-MPPI and NDL-249 and 100 times more
      potent than (S)-UH-301. 5-HT1A receptor agonists, e.g. 8-OH-DPAT and flesinoxan
      and partial agonists, e.g. pindolol, buspirone and ipsapirone had low potency in
      this in vivo assay. Spiperone and methiothepin inhibited the 3H-NAD-299
      accumulation at 10 micromol/kg s.c. The alpha1-adrenoceptor antagonist, prazosin
      at 2 micromol/kg s.c. increased significantly the specific accumulation of 3H-NAD
      299. Pretreatment of the mice with the non-selective, irreversible receptor
      antagonist, EEDQ produced a dose related long-lasting decrease in the
      accumulation of 3H-NAD-299. It is concluded that NAD-299 is a very suitable
      ligand for studies of 5-HT1A receptors in the brain in vivo.

PMID- 9650802
TI  - Improvement by FUB 181, a novel histamine H3-receptor antagonist, of learning and
      memory in the elevated plus-maze test in mice.
AB  - Effects of FUB 181 [3-(4-chlorophenyl)propyl-3-(1H-imidazol-4-yl)propyl ether], a
      novel histamine H3-receptor antagonist, on a scopolamine-induced learning deficit
      in the elevated plus-maze test were studied in mice. FUB 181 alone (2.5 and 5
      mg/kg, i.p.) ameliorated the scopolamine-induced learning deficit in mice. This
      effect was antagonized by BP 2.94 (10 mg/kg, i.p.), a prodrug of (R)-alpha
      methylhistamine (histamine H3-receptor agonist), and by ketotifen (4 mg/kg,
      i.p.), a histamine H1-receptor antagonist, both penetrating the blood-brain
      barrier. However, the ameliorating effect of FUB 181 (2.5 mg/kg) was not
      antagonized by either terfenadine (10 mg/kg, i.p.), a histamine H1-receptor
      antagonist with poor penetration of the blood-brain barrier, or zolantidine (20
      mg/kg, i.p.), a centrally effective histamine H2-receptor antagonist. In a
      biochemical study, FUB 181 had no significant effect on either acetylcholine or
      choline level in mice brain at the doses tested. These findings suggest that FUB
      181 increases the release of histamine by blocking presynaptic histamine H3
      autoreceptors, and that released histamine in turn activates postsynaptic H1 and
      H2 receptors, predominantly histamine H1 receptors, and in this fashion improves
      learning and memory in mice. Our findings also suggest that the histaminergic
      system may play an important role in learning and memory, and that FUB 181 may be
      a clinical candidate for the therapy of dementia.

PMID- 9650803
TI  - Role of vasopressin on excitatory amino acids mediated pressor responses in the
      periaqueductal gray area.
AB  - In order to evaluate the role played by vasopressin on pressor responses elicited
      by stimulation of the periaqueductal gray (PAG) area by excitatory amino acids we
      carried out in vivo studies in genetically vasopressin deficient rats
      (Brattleboro). Microinjections of 1-glutamic acid (glutamate, 0.6 to 60 nmol/rat)
      or N-methyl-d-aspartic acid (NMDA, 0.07 to 7 nmol/rat) into the PAG area of
      freely moving Brattleboro rats induced increases of arterial blood pressure
      values significantly lower than those obtained in Long Evans rats (control)
      (glutamate in Brattleboro rats: from +2+/-1 mmHg to 16+/-3 mmHg; glutamate in
      Long Evans rats: from +16+/-2 mmHg to +36+/-4 mmHg; NMDA in Brattleboro rats:
      from +5+/-2 mmHg to +34 +/-8 mmHg; NMDA in Long Evans rats: from +18+/-7 mmHg to
      80+/-9 mmHg; n=5). Similarly, in anaesthetized Brattleboro rats (urethane 1.2
      g/kg i.p.) pressor responses to NMDA microinjections (0.7 nmol/rat) into the PAG
      area were significantly lower than in Long Evans rats (controls) (+15+/-3 mmHg vs
      +24+/-4 mmHg). In Long Evans rats NMDA injection also reversed blood pressure
      decrease induced by ganglionic blocker, hexamethonium and/or losartan (3 mg/kg
      i.v.), an AT1 receptor antagonist. In Brattleboro rats, NMDA injection did not
      reverse blood pressure decreases induced by hexamethonium (5 mg/kg i.v.).
      Moreover, hexamethonium induced blood pressure decrease was not reversed by
      acetylcholine injection (137 nmol/rat) into the PAG area of anaesthetized Long
      Evans rats, but if injected before hexamethonium, acetylcholine was able to
      increase blood pressure (+25+/-3 mmHg). Our results document: i) the importance
      of the PAG area in the control of cardiovascular system; ii) the involvement of
      excitatory amino acids in the neural control of vasopressin release; iii) the
      close relationship between glutamate and vasopressin in the central blood
      pressure regulation.

PMID- 9650804
TI  - Effects of P2-receptor agonists on sympathetic neuroeffector transmission in the
      rat isolated anococcygeus muscle.
AB  - The effects of nicotinamide adenine dinucleotide phosphate (NADPH), alpha,beta
      methylene adenosine 5'-triphosphate (alpha,beta-MeATP), L-beta,gamma-methylene
      adenosine 5'-triphosphate (L-beta,gamma-MeATP), 2-methylthio-adenosine 5'
      triphosphate (MeSATP) and adenosine-5-O-(2'-thiodiphosphate) (ADPbetaS) were
      investigated on the contractions to electrical field stimulation in the rat
      anococcygeus muscle. Stimulation-induced contractions were not affected by L
      beta,gamma-MeATP (3-100 microM) or MeSATP (3-100 microM), but were enhanced by
      NADPH (10-100 microM), alpha,beta-MeATP (3-30 microM) and ADPbetaS (3-10 microM)
      in a concentration-dependent manner, and the enhancements were antagonised by the
      P2-receptor antagonist suramin (100 microM). The enhancement produced by
      alpha,beta-MeATP (10 microM) and ADPbetaS (10 microM) was also antagonised by
      pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (10 microM) and reactive
      blue 2 (100 microM). The enhancement produced by alpha,beta-MeATP (10 microM) was
      not altered by NG-nitro-L-arginine methyl ester (100 microM), desipramine (1
      microM) or idazoxan (0.1 microM) excluding, respectively, the possible
      involvement of nitric oxide, neuronal amine uptake or alpha2-autoinhibition of
      noradrenergic transmission. Contractions elicited by low (0.1 and 0.3 microM) but
      not by higher (1 and 3 microM) concentrations of exogenously applied
      noradrenaline were enhanced by alpha,beta-MeATP (10 microM). Neither the resting
      nor the stimulation-induced effluxes of radioactivity from [3H]-noradrenaline
      labelled anococcygeus muscles were affected by alpha,beta-MeATP (10-100 microM).
      The findings suggest that P2-receptors subserve the enhancing actions of NADPH,
      alpha,beta-MeATP and ADPbetaS on sympathetic neuroeffector transmission; however,
      the subtype of P2-receptor involved and its location remain unclear.

PMID- 9650805
TI  - Selective inhibition by riluzole of voltage-dependent sodium channels and
      catecholamine secretion in adrenal chromaffin cells.
AB  - We examined the effects of riluzole, a neuroprotective drug, on voltage-dependent
      Na channels, nicotinic receptors, and voltage-dependent Ca channels, as well as
      catecholamine secretion, in comparison with those of verapamil and nicardipine,
      in primary cultures of bovine adrenal chromaffin cells. Riluzole inhibited
      veratridine-induced 22Na influx via voltage-dependent Na channels even in the
      presence of ouabain, an inhibitor of Na,K-ATPase. Blockade of Na channels by
      riluzole was concentration-dependent with an IC50 of 5.3 microM. It was
      associated with a similar concentration-related reduction of veratridine-induced
      45Ca influx via voltage-dependent Ca channels, and of catecholamine secretion.
      Riluzole had no effect on 45Ca influx caused by high K, which directly activates
      voltage-dependent Ca channels, and on nicotine-induced 22Na influx, which passes
      through the nicotinic receptors. Verapamil and nicardipine attenuated 22Na influx
      caused by veratridine or nicotine at the same concentrations as they suppressed
      high K-induced 45Ca influx. The inhibitory effect of riluzole on veratridine
      induced 22Na influx disappeared at high concentrations of veratridine. A
      potentiation of veratridine (site 2 toxin)-induced 22Na influx caused by alpha
      scorpion venom (site 3 toxin), beta-scorpion venom (site 4 toxin), or brevetoxin
      PbTx-3 (site 5 toxin), occurred in the presence of riluzole in the same manner as
      in control cells. These results suggest that riluzole binds to the veratridine
      site in voltage-dependent Na channels. It does not impair the cooperative
      interaction between the functional peptide segments of Na channels, but
      selectively inhibits gating of Na channels, thereby reducing Ca influx via Ca
      channels and catecholamine secretion. In contrast, verapamil and nicardipine
      suppress Na influx both Na channels and nicotinic receptors.

PMID- 9650806
TI  - Effect of the Na+-channel modulator BDF 9148 on Ca2+-sensitivity and force of
      contraction of hypertrophic myocardium from transgene rats harboring the mouse
      Renin gene (TG(mREN2)27).
AB  - The present study aimed to investigate the inotropic effect of the Na+-channel
      modulator BDF 9148 in hypertrophic myocardium compared to control tissue. Thus,
      TG(mREN2)27 rats (TGR), a model with hypertension induced cardiac hypertrophy,
      was compared with age matched Sprague-Dawley rats (SPDR). The effect of BDF 9148
      (0.01-10 microM) on force of contraction (1 Hz, 37 degrees C), the force
      frequency relationship (0.5-7 Hz) and the frequency-dependent diastolic tension
      (0.5-7 Hz) was studied on left ventricular papillary muscles from SPDR and TGR.
      Chemically skinned muscle fibers of the same hearts were used to examine the
      influence of BDF 9148 on the Ca2+-sensitivity of the contractile proteins. For
      control the Ca2+-sensitizer EMD 57033 was examined. In addition the Na+/K+-ATPase
      activity was measured in both, SPDR and TGR. BDF 9148 showed a concentration
      dependent positive inotropic effect in SPDR and TGR cardiac preparations.
      Comparing SPDR and TGR, a higher effectiveness of BDF 9148 on TGR was found,
      while the potency was unchanged. With increasing stimulation rates a significant
      higher decrease in force of contraction in TGR compared to SPDR was observed. In
      addition, a significant higher increase in diastolic tension was found in TGR.
      After exposure to 1 microM BDF 9148 the decrease in force of contraction was
      significantly reduced in both SPDR and TGR, while only in TGR the increase in
      diastolic tension was reduced. BDF 9148 had no effect on the Ca2+-sensitivity or
      maximal developed tension of skinned fiber preparations from SPDR or TGR. In
      contrast, the Ca2+-sensitizer EMD 57033 increased the Ca2+-sensitivity. The
      activity of the Na+/K+-ATPase was significantly reduced in TGR compared to
      controls. CONCLUSIONS: The Na+-channel modulator BDF 9148 was more effective in
      hypertrophic compared to control myocardium in increasing force of contraction,
      enhancing frequency-dependent force generation and reducing diastolic tension.
      These effects were not mediated via interaction with the contractile apparatus.
      The enhanced effectiveness of Na+-channel modulation in hypertrophic myocardium
      could result from alterations of the Na+ homeostasis, i. e. a reduced Na+/K+
      ATPase activity.

PMID- 9650807
TI  - Inhibition of the delayed rectifier K current in guinea-pig cardiomyocytes by
      thiamine tetrahydrofurfuryl disulfide.
AB  - We examined effect of thiamine tetrahydrofurfuryl disulfide on
      electrophysiological characteristics of single atrial myocytes, obtained by
      digestion of guinea-pig heart, using collagenase. Membrane potential and ion
      channel current in the atrial myocytes were recorded by the patch clamp method.
      Thiamine tetrahydrofurfuryl disulfide prolonged action potentials at cycle
      lengths from 250 to 10,000 ms. The degree of thiamine tetrahydrofurfuryl
      disulfide-induced prolongation was similar among these cycle lengths. Thiamine
      tetrahydrofurfuryl disulfide inhibited the delayed rectifier K+ current, without
      affecting Ca2+ current and inward-rectifier K+ current. Thiamine
      tetrahydrofurfuryl disulfide blocked the delayed rectifier K+ current in voltage-
      and time-independent manner, indicating that thiamine tetrahydrofurfuryl
      disulfide blocked both subtypes of the delayed rectifier K+ current (rapid and
      slow components). Thiamine, the parent molecule of thiamine tetrahydrofurfuryl
      disulfide, blocked the delayed rectifier K+ current only when thiamine was
      applied intracellularly. Thiamine tetrahydrofurfuryl disulfide may be converted
      to thiamine in the cytoplasm, and then may block the the delayed rectifier K+
      channel from the intracellular side. Although thiamine tetrahydrofurfuryl
      disulfide (or thiamine) has some of the properties of class III antiarrhythmics
      agents, thiamine tetrahydrofurfuryl disulfide did not exhibit reverse use
      dependent prolongation of action potential.

PMID- 9650808
TI  - Autoreceptors can modulate 5-hydroxytryptamine release from porcine and human
      small intestine in vitro.
AB  - The effects of 5-hydroxytryptamine (5-HT) receptor agonists and antagonists were
      studied on the release of 5-HT from enterochromaffin cells of incubated strips of
      porcine and human small intestine. Tetrodotoxin (1 micromol/l) was present in the
      incubation medium to block neuronally mediated inputs to the enterochromaffin
      cells. The 5-HT1A receptor agonist (+)-8-hydroxy-dipropylaminotetralin (8-OH
      DPAT, 1 micromol/l) and the 5-HT2 receptor agonist alpha-methyl-5-HT (1
      micromol/l) increased 5-HT release by 40% in about 60% of the human preparations.
      These agonists showed no effect on 5-HT release in porcine intestinal mucosa. The
      5-HT3 receptor agonist 2-methyl-5-HT (3-100 micromol/l) increased 5-HT release in
      both species by 60% (pig) and 90% (man), respectively. These stimulatory effects
      were antagonized by tropisetron (10 nmol/l). The 5-HT4 receptor agonist 5
      methoxytryptamine (0.3-30 micromol/l) reduced 5-HT release by about 50% in both
      species. These inhibitory effects were antagonized by tropisetron (3 micromol/l).
      The basal outflow of 5-HT from the intestinal mucosa was not significantly
      affected by tropisetron (10 nmol/l; 3 micromol/l). The specific 5-HT4 receptor
      antagonist GR 113808 ((1-[2-methylsulphonyl)amino]ethyl]-4-piperidinyl]methyl-1
      methyl-1H-ind ole-3-carboxylate) (0.1 micromol/l) which by itself did not
      significantly affect 5-HT release from human duodenal specimens blocked the
      inhibitory effect of 5-methoxytryptamine (30 micromol/l). These findings indicate
      that stimulatory 5-HT3 and inhibitory 5-HT4 receptors are present on
      enterochromaffin cells of the porcine and human intestinal mucosa. Under the
      present experimental conditions endogenous 5-HT does not significantly activate
      these receptors. Stimulatory 5-HT1A and 5-HT2 receptors may additionally be
      present on human enterochromaffin cells.

PMID- 9650809
TI  - Phorbol ester-induced contractions of mouse detrusor muscle are inhibited by
      nifedipine.
AB  - The effects of phorbol esters on contractions of detrusor strips isolated from
      mouse urinary bladder were studied. Beta-phorbol-12,13-dibutyrate (beta-PDBu, 10
      nM) significantly enhances both the neurogenic and myogenic detrusor contractions
      to a similar extent. By contrast, an inactive isoform of protein kinase C (PKC)
      stimulation, alpha-phorbol-12,13-dibutyrate (100 nM) has no such enhancing effect
      on the muscle contraction. The effect of beta-PDBu was dependent on the
      extracellular Ca2+ concentration. Nifedipine (0.3 microM, a L-type Ca2+ channel
      blocker), staurosporine (1 microM) and bisindolylmaleimide I (microM, a selective
      PKC inhibitor) but not omega-conotoxin GVIA (an N-type Ca2+ channel blocker)
      abolished the enhancing effect of beta-PDBu. In other words, beta-PDBu failed to
      augment the nifedipine-insensitive component of the muscle contraction. Moreover,
      beta-PDBu not only enhances the muscle response induced by exogenous agonists
      (acetylcholine or ATP) and KCl but also increases the resting tone of detrusor
      muscle, an effect which is also inhibited by nifedipine and bisindolylmaleimide
      I. From these findings, it is concluded that the enhancing effect of beta-PDBu is
      due to activation of the L-type Ca2+ channel through phosphorylation by protein
      kinase C. This allows more Ca2+ influx from the extracellular medium, leading to
      an increase in the contractions of the mouse detrusor muscle.

PMID- 9650810
TI  - Protective effect of the combined treatment of pancreatic and neutrophil elastase
      inhibitors on acute pancreatitis elicited by lipopolysaccharide in rats given
      intraductal injection of taurocholate plus trypsin.
AB  - A severe acute pancreatitis was produced by intraperitoneal injection of
      lipopolysaccharide (LPS) in rats with preexisting hemorrhagic and necrotizing
      pancreatitis induced by retrograde injection of a 5% taurocholate plus 1% trypsin
      solution into the pancreatic duct. Mortality and time-course changes in
      pancreatic, hepatic, renal and pulmonary functions, and organ myeloperoxidase
      (MPO) levels were examined in this model. LPS at an intraperitoneal dose of 30
      mg/kg, which scarcely caused death and had no marked effect on serum parameters
      and organ MPO levels in rats without pancreatitis, increased the mortality in
      rats with taurocholate plus trypsin-induced pancreatitis. Pancreatic weight and
      ascitic volume increased in rats with taurocholate plus trypsin-induced
      pancreatitis regardless of the presence or absence of LPS. Serum amylase and
      lipase levels were also significantly increased in rats with induced
      pancreatitis, but was higher in the group given LPS. Serum glutamic oxaloacetic
      transaminase (GOT), glutamic pyruvic transaminase (GPT), blood urea nitrogen
      (BUN) and creatinine levels were significantly elevated in LPS-treated rats with
      induced pancreatitis, whereas levels in rats with induced pancreatitis not given
      LPS were only slightly elevated. Renal weight was also significantly increased in
      rats with induced pancreatitis despite the presence or absence of LPS. In LPS
      treated rats with induced pancreatitis, the arterial oxygen pressure, pulmonary
      weight and pulmonary MPO level were significantly elevated. However, the MPO
      level in the kidney in these rats was not different from that in control rats,
      indicating that the renal dysfunction was not produced by the infiltration of
      neutrophils into the kidney. Increase in the pancreatic MPO level was observed in
      rats with induced pancreatitis, but combination treatment with LPS did not raise
      it. Protective effects of prophylactic treatment of 2-(3-methylsulfonylamino-2
      oxo-6-phenyl-1,2-dihydro-1-pyridyl)-N-( 3,3,3-trifluoro-1-isopropyl-2
      oxopropyl)acetamide (compound 1), a neutrophil elastase inhibitor, and
      trifluoroacetyl-L-lysyl-L-alaninanilide hydrochloride (compound 2), a pancreatic
      elastase inhibitor, on mortality were also examined in this model. Results were
      compared with that of the combined treatment of compound 1 and compound 2. In LPS
      treated rats with taurocholate plus trypsin-induced pancreatitis, the combined
      treatment of compound 1 (2 mg/kg/h) and compound 2 (30 mg/kg/h) significantly
      reduced mortality, whereas single treatment of compound 1 or compound 2 did not
      show the beneficial effect. These results suggest that marked hepatic and renal
      dysfunction accompanies pancreatitis in this pancreatitis model rats, which may
      be good models for acute pancreatitis in humans. It is also suggested that
      neutrophil and pancreatic elastases may be synergistically involved in the
      pathogenesis of acute pancreatitis in this model.

PMID- 9650811
TI  - Suppression of leukotriene B4 and tumour necrosis factor alpha release in acute
      inflammatory responses by novel prenylated hydroquinone derivatives.
AB  - A series of prenyl hydroquinone derivatives synthesized as structural analogs of
      marine products were tested for their effects on inflammatory responses in vitro
      and in vivo. 2-Prenyl-1,4-hydroquinone (H1), 2-diprenyl-1,4-hydroquinone (H2), 2
      triprenyl-1,4-hydroquinone (H3) and 2-tetraprenyl-1,4-hydroquinone (H4) scavenged
      reactive oxygen species and inhibited 5-lipoxygenase (5-LO) activity in human
      neutrophils. The inhibition of 5-LO activity was demonstrated in vivo in the
      mouse air pouch injected with zymosan and arachidonic acid-induced ear
      inflammation. The four compounds suppressed the production of tumour necrosis
      factor alpha (TNFalpha) in J774 cells stimulated with lipopolysaccharide (LPS)
      and also in vivo in the mouse air pouch injected with zymosan. In addition, all
      prenyl-hydroquinones inhibited the release of nitrite and PGE2 in LPS-stimulated
      J774 cells, without direct effects on cyclo-oxygenase-1 (COX-1), cyclo-oxygenase
      2 (COX-2) or inducible nitric oxide synthase (iNOS) activities in several cell
      free systems. The reduction in the length of the lateral chain in prenyl
      hydroquinones (1-4 isoprene units) with respect to their marine analogs (7-8
      isoprene units) has improved the anti-inflammatory activity of this class of
      compounds. Marine natural products may be a model to design new anti-inflammatory
      agents.

PMID- 9650812
TI  - Inhibition of interleukin-4 and interleukin-13 release from immunologically
      activated human basophils due to the actions of anti-allergic drugs.
AB  - Human basophils have recently been shown to rapidly produce and release
      interleukin (IL-)4 and IL-13 as well as histamine and eicosanoids. Since both IL
      4 and IL-13 can initiate and maintain late phase allergic reactions we addressed
      whether some widely used anti-allergic drugs can inhibit the anti-IgE induced
      release of these cytokines from enriched human basophils. Basophils were enriched
      (47-92% purity) by Ficoll density centrifugation followed by elutriation and
      negative selection of contaminating cells using immunomagnetic beads. Basophils
      were stimulated with sub-optimal dilutions of anti-IgE in the presence or absence
      of various drugs and the release of histamine and cytokines were measured after
      30 min and 4 h, respectively. The beta-2 agonist salmeterol, the H1-receptor
      antagonist terfenadine and the phosphodiesterase inhibitor theophylline inhibited
      the release of IL-4 and IL-13 by more than 50% following 4 h of basophil
      stimulation with anti-IgE. These drugs also inhibited the release of histamine
      following 30 min stimulation, although with less efficacy than for IL-4 and IL
      13. Short preincubation of basophils with salmeterol or terfenadine before
      stimulation gave rise to significantly greater inhibition of histamine release
      but had less effect on the inhibition of cytokine release. The effects of
      theophylline, however, were not significantly affected by preincubation of the
      cells with the drug. In contrast to the aforementioned drugs, salbutamol and
      cetirizine were ineffective at inhibiting both histamine and cytokine release
      from basophils. These results suggest that a number of anti-allergic drugs may
      mediate their effects, in part, in reducing late phase allergic responses due to
      their actions on IL-4 and IL-13 secretion from basophils.

PMID- 9650813
TI  - Nitric oxide inhibits isoprenaline-induced positive inotropic effects in normal,
      but not in hypertrophied rat heart.
AB  - Evidence has accumulated that, in the rat heart, nitric oxide (NO) inhibits beta
      adrenoceptor-mediated positive inotropic effects. The aim of this study was to
      investigate whether this effect of NO may be altered in cardiac hypertrophy. For
      this purpose we studied the effects of the NO-donor SNAP (S-nitroso-N-acetyl-D,L
      penicillamine) on isoprenaline-induced positive inotropic effects in left
      ventricular strips from three models of cardiac hypertrophy: a) 12-16 weeks old
      male spontaneously hypertensive rats (SHR) vs. age-matched normotensive Wistar
      Kyoto (WKY) rats, b) six weeks old male Wistar WKY-rats sub-totally
      nephrectomized (SNX) 7 weeks after SNX vs. sham-operated rats (SOP) and c) four
      weeks old male Wistar WKY-rats supra-renal aortic-banded (AOB, band diameter 1.0
      mm) 8 weeks after AOB vs. SOP. In all three models of cardiac hypertrophy the
      heart weight/body weight ratio was significantly higher than in their respective
      controls. On isolated electrically driven ventricular strips isoprenaline (10(
      10)-10(-5) M) caused concentration-dependent increases in force of contraction.
      Maximal increases (Emax) were similar in SHR vs. WKY-rats, but reduced in SNX-
      (2.9+/-0.29 vs. 5.1+/-0.34 mN, p<0.01) and AOB-rats (2.3+/-0.37 vs. 4.2+/-0.33
      mN, p<0.01). In control rats (WKY and the respective SOP) the NO-donor SNAP (10(
      5) M) caused a significant rightward-shift of the concentration-response curve
      for isoprenalinel; this rightward-shift could be inhibited by methylene blue (10(
      5) M). In ventricular strips of SHR, SNX- and AOB-rats, however, 10(-5) M SNAP
      failed to significantly affect isoprenaline-induced positive inotropic effect. We
      conclude that in cardiac hypertrophy effects of NO are attenuated. Such an
      impairement of the NO-system could contribute to the development and/or
      maintenance of cardiac hypertrophy.

PMID- 9650814
TI  - The role of carbon monoxide in the regulation of neuroendocrine function.
AB  - This paper discusses the current evidence supporting the notion that endogenous
      carbon monoxide (CO) is a modulator of neuroendocrine function. CO is normally
      formed in the body during the enzymatic catabolism of heme moieties by heme
      oxygenase (HO). Three HO isoforms have been described to date: HO-1, HO-2 and HO
      3. In the brain, CO is principally generated by HO-2 but, in discrete brain areas
      such as the paraventricular nuclei of the hypothalamus, a role for HO-1 is also
      possible. Moreover, under pathological conditions, the latter isoform is
      expressed by activated glial cells. The possible contribution by the recently
      described HO-3 remains to be established. Once formed, CO exerts its biological
      effects mainly via the activation of soluble guanylyl cyclase, but alternative
      signaling mechanisms, such as the activation of cyclooxygenase or the inhibition
      of cytochrome P450, have also been reported. In in vitro studies, the formation
      of CO within the hypothalamus has been associated with inhibition of the release
      of hormones such as corticotropin-releasing hormone, arginine vasopressin and
      oxytocin involved in hypothalamo-pituitary-adrenal axis activation and,
      conversely, with stimulation of luteinising hormone-releasing hormone release,
      thus suggesting that the gas may have a neuroendocrine role which may be to
      prevent over-exuberant activation of the hypothalamo-pituitary-adrenal axis and
      inhibition of reproductive processes within the hypothalamus during stress. At
      present, however, the possible pathophysiological relevance of the in vitro
      observations remains to be demonstrated.

PMID- 9650815
TI  - Effect of homologous interleukin-1, interleukin-6 and tumor necrosis factor-alpha
      on the core body temperature of mice.
AB  - Lipopolysaccharide (LPS) and homologous cytokines were tested for their effect on
      core temperature in mice using battery-operated telemetric devices placed in the
      peritoneal cavity. One microgram LPS injected intraperitoneally (i.p.) induced a
      biphasic effect on core body temperature (Tc), a rapid decrease in Tc with a peak
      around 30-45 min followed by a prolonged rise around 150-300 min. When a higher
      dose of LPS (5 microg) was used, the hypothermia was increased in magnitude and
      lasted much longer, and no fever was observed. Both the decrease and the increase
      in Tc caused by LPS were prevented by pretreating the mice with indomethacin, a
      cyclooxygenase inhibitor, but not by a nitric oxide synthase inhibitor. Mouse
      interleukin-1beta (mIL-1beta, 100 ng, i.p.) induced changes resembling those to
      LPS, a short-lived decrease in Tc, followed by a small increase. When 1 microg
      mIL-1beta was injected a profound hypothermia lasting more than 3 h was observed.
      Mouse IL-6 (1 microg) failed to alter core temperature after either intravenous
      (i.v.) or i.p. administration. Human IL-6 was also ineffective. Recombinant mouse
      tumor necrosis factor-alpha (mTNFalpha) also failed to alter the core temperature
      of mice when injected at a dose of 1 microg (i.p. or i.v.). However, a higher
      dose of mTNFalpha (5 microg i.p.) caused a short-lived decrease in Tc, followed
      by a small increase. Similar results were obtained with LPS and the cytokines in
      C57Bl/6J mice, except that mIL-1beta was ineffective in this strain. These
      results indicate that the endocrine, neurochemical and behavioral responses to IL
      1, IL-6 and TNFalpha administration cannot be explained by changes in Tc,
      although they may contribute to them. They also suggest that IL-1beta may account
      for the fever observed following LPS, but that these cytokines are probably not
      the only factors involved in LPS-induced changes in Tc.

PMID- 9650816
TI  - Granulocyte-macrophage colony stimulating factor suppresses LHRH release by
      inhibition of nitric oxide synthase and stimulation of gamma-aminobutyric acid
      release.
AB  - Several cytokines produced by immune cells act within the hypothalamus and/or on
      the pituitary to produce the pattern of pituitary hormone secretion that
      characterizes infection. Granulocyte-macrophage colony stimulating factor (GMCSF)
      was first described as a hematopoietic cytokine; however, its synthesis is also
      stimulated during infection, and it has been found in glia in the brain. Previous
      research indicates that interleukin-1 inhibits release of luteinizing hormone
      releasing hormone (LHRH) both in vivo and in vitro. In the present study, we
      determined that GMCSF inhibited the release of LHRH in vitro and evaluated the
      mechanisms involved. After a 1-hour preincubation in Krebs-Ringer bicarbonate
      glucose buffer (KRB), medial basal hypothalamic explants were incubated in KRB
      together with recombinant murine GMCSF for 0.5 h in a Dubnoff metabolic shaker
      (50 cycles/min) in an atmosphere of 95% O2/5% CO2. LHRH release into the media
      was determined by radioimmunoassay. At concentrations of 10(-12) and 10(-11) M,
      GMCSF significantly inhibited LHRH release. There was a U-shaped dose-response
      curve and LHRH release was not inhibited at lower or higher cytokine
      concentrations. The inhibition was specific since it was completely blocked by
      GMCSF antiserum. Since sodium nitroprusside (NP; 300 microM), a releaser of
      nitric oxide (NO), stimulates LHRH, presumably by acting within the LHRH neurons,
      we examined the effect of GMCSF (10(-11) M) on NP-induced LHRH release. It
      completely suppressed NP-induced release of LHRH. Bicuculline (10(-5) M), a gamma
      aminobutyric acid (GABA) receptor antagonist, partially reversed the inhibitory
      effects of GMCSF on LHRH release. This dose completely reversed the suppression
      of LHRH release induced by GABA. The present results indicate that the inhibitory
      effects of GMCSF on LHRH release are partially caused by blockade of NO-induced
      LHRH release by its activation of GMCSF receptors on GABAergic neurons. The
      stimulated release of GABA acts on the GABA-a receptors on the LHRH terminals to
      inhibit their response to NO. At the end of the experiment, NO synthase (NOS)
      activity was measured in the tissue homogenate by the citrulline method. NOS
      activity was highly significantly reduced by GMCSF (10(-11) M) indicating that
      part of its suppressive action on LHRH release is mediated by reduction in NOS
      activity in the medial basal hypothalamus.

PMID- 9650817
TI  - Stimulation of T-cell proliferation by pancreastatin and its C-terminal fragment
      (33-49).
AB  - We have studied the effect of pancreastatin and its C-terminal fragment (33-49)
      on mitogen-stimulated T lymphocyte proliferation. In a concentration range from
      10(-12) to 10(-8) M they exhibit a dose-dependent stimulatory effect on
      concanavalin A-induced response with the maximal effect at 10(-8) M
      concentration. They were inactive in response to a B-cell mitogen,
      lipopolysaccharide, which points to an involvement of T but not B lymphocytes in
      their response. Pancreastatin can still produce a stimulatory effect when added
      18 h after incubation of cultures with concanavalin A and apparently uses a
      diacylglycerol independent mechanism. When cells were preincubated for 4, 16 or
      24 h with pancreastatin or its fragment and then stimulated with concanavalin A,
      a ten times lower concentration of peptides was needed (10(-9) M) to obtain the
      maximal response. This suggests that resting cells are more sensitive to
      pancreastatin and its fragment. Both peptides exhibit a very similar
      pharmacological profile, indicating that the C-terminal part of the molecule is
      responsible for the effect on T-cell proliferation.

PMID- 9650818
TI  - Direct morphological evidence of neuroimmunomodulation in colonic mucosa of
      patients with Crohn's disease.
AB  - Different neuropeptide-containing nerve fibers were investigated to clarify their
      role in the pathogenesis of Crohn's disease (CD) using immunohisto- and
      immunocytochemical techniques. Specimens were obtained from patients with CD from
      grossly affected colonic regions, from biopsies obtained from patients with CD
      treated with mesalazine and from control individuals. Quantitative analysis was
      made for the changes of the number of nerve terminals and their vesicle contents.
      The distribution pattern of all immunoreactive (IR) nerve fibers was similar both
      in the control and in the surgical specimens as well as in the biopsies obtained.
      The number of the synapses, the IR nerve fibers and their vesicle content were
      markedly decreased in the grossly affected colonic regions. Some degenerated
      axons were found in close proximity to the plasma cells. Immunocytochemistry
      demonstrated that substance P, vasoactive intestinal polypeptide and somatostatin
      IR nerve fibers were in direct contact with the plasma cells, lymphocytes and
      other immunocompetent cells. The gap between the membranes of immunoreactive
      nerve terminals and immunocompetent cells was 20-200 nm, in a few cases even
      less. In the mesalazine-treated group the number of the IR nerve terminals as
      well as their vesicle content was increased. These results suggest that changes
      in the number of different neuropeptide-containing nerve terminals and their
      content might alter the neuroimmunological processes, because these peptides are
      known to be immunoregulators.

PMID- 9650819
TI  - Administration of interleukin-1 into the hypothalamic paraventricular nucleus
      induces febrile and behavioral effects.
AB  - Administration of interleukin-1 (IL-1) into the cerebral ventricles produces
      marked physiological and behavioral effects. However, the precise locations
      within the central nervous system that mediate these effects have not been
      determined. Previous studies indicated that IL-1 induces neurophysiological,
      neurochemical and neuroendocrine changes within the hypothalamic paraventricular
      nucleus (PVN). These findings suggest that the PVN is also involved in mediating
      the behavioral effects of IL-1. This hypothesis was tested by examining the
      effects of administration of IL-1beta (10 or 50 ng/rat) or saline, either
      intracerebroventricularly or into the PVN, on fever and several behavioral
      parameters. IL-1beta, administered into both locations, induced a comparable
      suppression of motor activity, reduction in food and saccharine consumption, and
      loss of body weight. The febrile response to IL-1beta, assessed by a
      biotelemetric system, was significantly greater following administration into the
      PVN than into the lateral ventricle. Additionally, IL-1 administration into
      adjacent thalamic locations had no febrile or behavioral effects. These findings
      suggest that the PVN may be one of the brain structures involved in mediating the
      response to IL-1.

PMID- 9650820
TI  - Vagal afferent nerve fibres contact mast cells in rat small intestinal mucosa.
AB  - Mast cells degranulate when exposed to specific antigens (via surface bound IgE),
      resulting in the release of numerous pro-inflammatory mediators. Neuroregulatory
      substances also activate mast cells, and may effect differential mediator
      release, without degranulation, suggesting a role for nerves in modulating mast
      cell activity. We previously investigated the microanatomical relationships of
      intestinal mucosal mast cells (IMMC) with nerves and found extensive associations
      in the intestinal mucosae of rats and humans. The origins of nerves that contact
      IMMC have not been determined; however, recent morphological and functional
      studies suggest the possibility that the vagus nerve might be involved. In the
      current study we show that vagal afferent fibers (labeled by injecting DiI into
      the nodose ganglion) penetrate to the tips of jejunal villi; and that some of
      these nerves make intimate contact with IMMC. These data provide the
      microanatomical basis for direct neural communication between the central nervous
      system (CNS) and mast cells in the gastrointestinal mucosa.

PMID- 9650821
TI  - Centrally mediated inhibition of local inflammation by ciliary neurotrophic
      factor.
AB  - Since ciliary neurotrophic factor (CNTF) inhibits the production of TNF and
      activates the hypothalamus-pituitary-adrenal axis (HPAA), we investigated whether
      CNTF can produce antiinflammatory actions and whether it may act through a
      central mechanism, using the murine air pouch model of inflammation. In this
      model, inflammation is evaluated by measuring the induction of TNF and IL-6 as
      well as cell recruitment in the pouch fluid 24 h after carrageenan.
      Intracerebroventricular injection, but not intravenous or local injection of CNTF
      markedly inhibited inflammation. This was associated with high serum
      corticosterone levels, and antiinflammatory action was not observed in
      adrenalectomized mice, indicating that an intact HPAA is required. A CNTF
      receptor antagonist increased carrageenan inflammation, suggesting that
      endogenous CNTF might have a centrally mediated antiinflammatory role.

PMID- 9650822
TI  - Possible control of cell death pathways in ataxia telangiectasia. A case report.
AB  - Peripheral blood monocytes (PBMCs) obtained from a boy with the
      neuroimmunodegenerative syndrome of ataxia telangiectasia (AT) failed to
      aggregate or replicate efficiently when mitogenically activated under serum
      depleted conditions. These cells rapidly swelled, then slowly shrank, and
      flattened as they excreted vesicles containing chromatin. This accelerated cell
      death with loss of homoadhesiveness could be prevented in vitro in most of the
      homozygous PBMCs by adding large amounts of autologous serum or by adding
      mixtures of Th1 cytokines, serum factors, and redox agents. However, even in high
      serum media containing added cytokines, 20-30% of the homozygous PBMCs quickly
      flattened, produced minicells, and died. Since the defective functions of the
      human ataxia-telangiectasia nuclear kinase gene (ATM) could be bypassed in vitro
      in these defective AT PMBCs by addition of appropriate cytokines and redox
      survival factors, it may be possible to slow the progressive losses of ATM
      deficient lymphoid cells seen in vivo. Since the neuronal degeneration in AT, as
      seen in the retrovirus-induced neuroimmunodegenerative syndromes, may also be a
      consequence of impairment of the central and peripheral immune system, it may
      become possible to prevent the neurodegeneration in AT by using signaling
      therapies that upregulate the ATM-induced signal deficiencies in the developing
      immune system.

PMID- 9650823
TI  - Molecular biology of opioid receptors: recent advances.
AB  - Endogenous opioid peptides and opiates like morphine produce their
      pharmacological effects through the membrane bound opioid receptors. These
      receptors belong to a superfamily of G-protein-coupled receptors, all of which
      possess seven membrane-spanning regions. Structure-activity relationship studies
      of opioids opened up new avenues for the pharmacological characterization of the
      opioid receptors. As a further advancement in this direction, molecular cloning
      has led to the identification of three different types of opioid receptors -- OP1
      (delta), OP2 (kappa) and OP3 (mu) -- thereby supporting the results of earlier
      pharmacological studies which postulated their existence. The three opioid
      receptors are highly homologous. Consequent to the development of highly specific
      and selective agonists and antagonists, it was proposed that the three types of
      opioid receptors could be further categorized into different subtypes. However,
      the molecular biology data generated so far do not support the presence of the
      various subtypes of the three well-characterized opioid receptors. Recent strides
      towards the advancement of our knowledge relating to the molecular biology of
      these receptors have been reviewed in this article.

PMID- 9650824
TI  - Afferent signals to the CNS appear not to condition the modulation of interleukin
      1 receptors in the hippocampus.
AB  - Conditioned alteration of natural killer (NK) cell activity was used as an
      indicator of the functional bidirectional communication between the immune and
      central nervous systems. Poly I:C and lipopolysaccharide (LPS) from Escherichia
      coli and Salmonella typhimurium were used as unconditioned stimuli and odor of
      camphor as the conditioned stimulus. An attempt was made to demonstrate the role
      of central interleukin (IL-1) receptors in this communication process. Brain IL-1
      receptors were down-regulated by treatment with 50 microg/mouse of LPS from S.
      typhimurium, but not with the same dose of LPS from E. coli or poly I:C. A
      significant level of conditioned augmentation of NK cell activity was observed
      with poly I:C. Conditioned alteration in NK cell activity was also observed with
      LPS from E. coli, but at much lower level than poly I:C. NK cell activity was not
      conditioned with LPS from S. typhimurium at the same dose as E. coli LPS, but
      conditioned enhancement of NK cell activity was observed with a higher dose (100
      microg) of S. typhimurium LPS. These results suggest that modulation of central
      IL-1 receptors do not seem to play a role in the conditioned augmentation of NK
      cell activity.

PMID- 9650825
TI  - Bradykinin receptors and their antagonists.
AB  - Bradykinin and related kinins act on two receptor types, named B1 and B2.
      Initially identified in classical bioassays, these receptors have been cloned and
      characterized in binding assays performed on plasma membranes of cells expressing
      the native or the transfected human kinin B1 or B2 receptor types. The two
      classification criteria recommended by Schild, namely the order of potency of
      agonists and the actual affinity of antagonists have been found to be applicable
      for receptor classification based not on data only from bioassays but also from
      other approaches (binding assays, molecular biology techniques). The order of
      potency for agonists was found with naturally occurring peptides (the kinins,
      their desArg9-metabolites) and with selective agonists (e.g., [Hyp3]bradykinin,
      [Aib7]bradykinin): the findings obtained with agonists could be validated with
      various antagonists. Critical evaluation of the initial compounds, typified by D)
      Arg-[Hyp3, D-Phe7]bradykinin, has indicated that they are short-acting, partial
      agonists, non-selective for the bradykinin B2 receptor because they can be
      metabolized to desArg9-fragments that act on the kinin B1 receptor. Use of such
      compounds has given rise to misunderstandings, especially with regard to new
      receptor types (e.g., type B3), the existence of which was not confirmed by
      molecular cloning. A second generation of antagonists, represented by D
      Arg[Hyp3,Thi5,D-Tic7,Oic8]bradykinin (HOE 140) has been found resistant to
      degradation, long-acting in vivo, selective and specific for the B2 receptor and
      potent in all species tested. HOE 140 has been used successfully in basic
      pharmacology, in animal physiopathologies involving kinins and their receptors
      and even in clinical studies. A third generation of non-peptide B2 receptor
      antagonists, whose prototype is FR 173657 ((E)-3-(6-acetamido-3-pyridyl)-N-[N-2-4
      dichloro-3-[(2-methyl-8-quinolin yl)oxymethyl]phenyl]-N-methylamino carbonyl
      methyl]acrylamide) is now emerging and may represent substantial progress since
      FR 173657 is a potent orally active, selective and specific antagonist of the
      human and other species B2 receptors. There is also progress regarding
      antagonists for the B1 receptor. The initial compounds, especially Lys
      [Leu8]desArg9-bradykinin remain among of the most potent, specific and selective
      B1 antagonists which, however, show partial agonistic effects in some B1 receptor
      subtypes (e.g., the mouse). Progress has been made with AcLys-[D-betaNal7,
      Ile8]desArg9-bradykinin (R 715) and Lys-Lys-[Hyp3, Cpg5, D-Tic7,Cpg8]desArg9
      bradykinin (B 9958) which are pure B1 antagonists in humans and rabbits; both
      peptides have shown resistance to degradation by peptidases and have little if
      any, residual agonistic activity on mouse and rat B1 receptors. No non-peptide
      antagonists are yet available for the B1 receptor.

PMID- 9650826
TI  - Basal nitric oxide release differentially modulates vasodilations by pinacidil
      and levcromakalim in goat coronary artery.
AB  - In the current investigation, the role of basal nitric oxide (NO) in modulating
      the vasorelaxant responses to pinacidil and levcromakalim was examined in goat
      isolated coronary artery. Pinacidil (10(-8) 10(-4) M) elicited concentration
      dependent relaxations of the coronary artery ring segments (with intact
      endothelium) constricted with 30 mM K+ saline solution. The EC50 of the
      vasodilator was 2.57 x 10(-6) M (95% CL, 1.9-3.46 x 10(-6) M). The removal of
      endothelium by mechanical rubbing caused a rightward shift in the concentration
      response curve of pinacidil with a corresponding increase in EC50 value (1.90 x
      10(-5) M; 95% CL, 1.12-3.23 x 10(-5) M). Similar to endothelium removal,
      treatment of endothelium-intact rings either with the NO synthesis inhibitor L
      NAME (NG-nitro-L-arginine methyl ester; 3 x 10(-5) M) or the guanylate cyclase
      inhibitor, methylene blue (3 x 10(-6) M) resulted in a marked inhibition in the
      relaxant responses to pinacidil. Hence, the EC50 values of the potassium channel
      opener were significantly higher in tissues treated either with L-NAME (7.41 x
      10(-6) M; 95% CL, 6.02-9.12 x 10(-6) M) or methylene blue (2.29 x 10(-5) M; 95%
      CL, 1.58-3.31 x 109-5) M) as compared to untreated controls. The ATP-sensitive
      potassium (KATP) channel blocker glibenclamide, which caused a significant
      rightward shift in the concentration-relaxation curve of pinacidil in control
      tissues, was found to be less potent in antagonising the relaxant responses of
      the KATP channel opener in endothelium-denuded rings and in rings with intact
      endothelium but treated with either L-NAME or methylene blue. In contrast to the
      observations made with pinacidil, the vasodilator responses to another KATP
      channel opener, levcromakalim, were potentiated in the absence of basal NO. Thus,
      the EC50 of levcromakalim was 1.33 x 10(-8) M (95% CL, 0.8-2.21 x 10(-8) M) in
      control tissues with intact endothelium, which was significantly higher than
      those obtained in endothelium-deprived rings (4.81 x 10(-9) M; 95% CL, 4.04-5.73
      x 10(-9) M) or endothelium intact rings treated either with L-NAME (2.63 x 10(-9)
      M; 95% CL, 1.58-4.36 x 10(-9) M) or methylene blue (2.82 x 10(-9) M; 95% CL, 1.7
      4.68 x 10(-9) M). The selective modulation by basal NO of the arterial
      relaxations elicited with the KATP channel openers was evident from the findings
      that papaverine-induced relaxations were not affected in the absence of basal NO.
      Taken together, the results of the present study suggest that basal NO
      differentially modulates the interaction of pinacidil and levcromakalim with the
      KATP channels in goat coronary artery through a cGMP-dependent pathway.

PMID- 9650827
TI  - Interaction of endothelial eccrine mechanisms and human adrenomedullin on
      vascular resistance in canine bone.
AB  - Adrenomedullin is a novel peptide known to be one of the most potent vascular
      smooth muscle relaxing agents in vivo. The aim of this study is to investigate
      the effect of adrenomedullin in relation to nitric oxide, prostaglandins and
      endothelium-derived hyperpolarized factor (EDHF). A 0.1-ml bolus of 1 nmol human
      adrenomedullin is a potent inhibitor of the pressor response to exogenous
      norepinephrine infusion in an ex vivo canine tibia perfusion model for a duration
      of at least 70 min (P < 0.005). This attenuation of vascular smooth muscle
      contraction occurs even when nitric oxide production is blocked by NG-monomethyl
      L-arginine acetate (L-NMMA) infusion and EDHF is blocked by tetraethylammonium
      infusion, although the effect is of shorter duration (at least 10 min).
      Indomethacin as well does not affect the suppression of norepinephrine-induced
      vascular smooth muscle contraction. Based on these data, human adrenomedullin has
      both nitric oxide- and EDHF-dependent mechanism as well as a nitric oxide- and
      EDHF-independent mechanism.

PMID- 9650828
TI  - 5-hydroxydecanoate selectively reduces the initial increase in extracellular K+
      in ischemic guinea-pig heart.
AB  - The aim of the present study was to determine the effect of 5-hydroxydecanoate (5
      HD) on extracellular K+ levels during global ischemia for 30 min employing K+
      sensitive electrodes in isolated guinea-pig hearts. 5-HD (100 microM) reduced the
      K+ accumulation during the early period of ischemia, but did not inhibit the
      elevation of extracellular K+ in the latter half of the ischemic period which was
      selectively enhanced by ouabain (3 microM). Thus, 5-HD appears to exert a similar
      mode of action as glibenclamide on extracellular K+ accumulation in the ischemic
      guinea-pig hearts. The present study also strengthens the previous conclusion
      that an ATP-sensitive K+ channel contributes only to the initial increasing phase
      of extracellular K+ accumulation during ischemia in guinea-pig hearts.

PMID- 9650829
TI  - Effect of lipo-prostaglandin E1 on crescentic-type anti-glomerular basement
      membrane nephritis in rats.
AB  - The antinephritic effect of lipo-prostaglandin E1, prostaglandin E1 ((1R,2R,3R)-3
      hydroxy-2-[(E)-(3S)-3-hydroxy-1-octenyl]-5-oxocyclopent ane heptanoic acid)
      incorporated in lipid microspheres was investigated using an experimental model
      of nephritis, crescentic-type anti-glomerular basement membrane nephritis. Lipo
      prostaglandin E1 was given i.v. twice a day at 20, 40 and 80 microg/kg and
      azathioprine, an immunosuppressive agent, at 20 mg/kg was given p.o. once daily
      from the autologous phase, in which glomerulonephritis was fully developed (the
      21 st day after injection of the anti-glomerular basement membrane serum), to the
      50th day. Lipo-prostaglandin E1 (40 and 80 microg/kg x 2 per day) significantly
      inhibited the development of glomerular alterations as well as the elevation of
      proteinuria and plasma creatinine. Lipo-prostaglandin E1 (20 microg/kg x 2 per
      day) and azathioprine (20 mg/kg per day) significantly inhibited only the
      glomerular histopathological changes. Lipo-prostaglandin E1 at three doses
      significantly decreased the deposition of both rabbit immunoglobulin G and rat
      immunoglobulin G on the glomerular basement membrane in nephritic rats, but
      azathioprine apparently inhibited only the deposition of rat immunoglobulin G. A
      single administration of lipo-prostaglandin E1 inhibited the elevation of
      platelet aggregation and restored the decrease in renal tissue blood flow in
      nephritic rats. In addition, a single administration of lipo-prostaglandin E1
      inhibited the elevation of glomerular thromboxane B2 and 6-keto prostaglandin
      F1alpha production in nephritic rats. These results suggest that lipo
      prostaglandin E1 may be an effective agent for the treatment of
      glomerulonephritis. Its antinephritic effect may be due to the inhibition of
      platelet aggregation, an increase in renal tissue blood flow, a decrease in
      rabbit and rat immunoglobulin G deposition, and amelioration of the abnormal
      metabolism of arachidonic acid.

PMID- 9650830
TI  - Antipyretic activity of cinnamyl derivatives and related compounds in influenza
      virus-infected mice.
AB  - Kakkon-to is composed of seven medicinal herbs and exhibited novel antipyretic
      activity by suppressing interleukin-1alpha production responsive to interferon in
      a murine intranasal influenza virus infection model. Using this model,
      antipyretic compounds with such novel biological activities were characterized
      from the herbs. The organic solvent-extractable fractions of Cinnamomum cassia
      among the herbs showed antipyretic activity. We selected six antipyretic
      compounds from 48 cinnamyl derivatives and related compounds that may be mainly
      involved in the fractions. Their antipyretic activity was significantly
      correlated with interleukin-1alpha regulatory activity. Four of them suppressed
      interleukin-1alpha production to a basal level and showed different mode of
      antipyretic action from that of aspirin in interleukin-1alpha-injected mice.
      Structure-bioactivity relationship of the four suggested that an ester bond
      played an important role for both antipyretic and interleukin-1alpha regulatory
      activities. These compounds may be useful in analyzing interleukin-1alpha
      producing cells in fever production and the mechanism of defervescence by
      suppressing interferon-induced interleukin-1alpha production.

PMID- 9650831
TI  - Cyclic AMP accumulation in rat soleus muscle: stimulation by beta2- but not beta3
      adrenoceptors.
AB  - The beta-adrenoceptor subtypes involved in cyclic AMP accumulation in rat soleus
      muscle were studied using beta1- beta2- and beta3-adrenoceptor agonists and
      antagonists. Responses to (-)-isoprenaline were antagonised by (-)-propranolol (p
      KB = 8.32 at 0.1 microM) and by erythro-DL-1(7-methylindian-4-yloxy)-3
      isopropylaminobuta n-2-ol (+/-)-ICI 118551) (pKB = 9.38 at 10 nM and 9.65 at 100
      nM) but not by 2-hydroxy-5(2-((2-hydroxy-3-(4-((1-methyl-4-trifluoromethyl)1H
      imidazole -2-yl)-phenoxy)propyl)amino)ethoxy)-benzamide monomethane sulfonate
      ((+/-)-CGP 20712A at 10 nM or 100 nM). The beta3-adrenoceptor agonist sodium-4-[
      2[-2-hydroxy-2-(-3-chlorophenyl)ethylamino]propyl]phenoxya cetate (BRL 37344 at
      10 pM or 10 microM) caused no significant change in basal cyclic AMP levels and
      had no effect on the level of cyclic AMP accumulation stimulated by (-)
      isoprenaline, zinterol or forskolin. (-)-Isoprenaline pretreatment (400 microg
      kg(-1) h(-1), 14 days) abolished responses to (-)-isoprenaline (10 microM) and
      zinterol (1 microM) while BRL 37344 had no effect in either isoprenaline or
      vehicle-treated groups. These results show that beta3-adrenoceptor agonists do
      not stimulate cyclic AMP accumulation in rat soleus muscle and that (-)
      isoprenaline induced increases in cyclic AMP levels are mediated predominantly by
      beta2-adrenoceptors. This suggests that the previously reported increase in
      glucose uptake by beta3-adrenoceptor agonists in skeletal muscle does not involve
      direct stimulation of adenylate cyclase.

PMID- 9650832
TI  - The properties of caffeine- and carbachol-induced intracellular Ca2+ release in
      mouse bladder smooth muscle cells.
AB  - Freshly dissociated bladder smooth muscle cells of mice developed spontaneous,
      caffeine- (ICAF) and carbachol-induced (ICCh) currents under voltage-clamped
      conditions. Spontaneous currents, ICAF and ICCh were blocked with
      tetraethylammonium at 3 x 10(-4)-10(-2) M but were resistant to both
      charybdotoxin (10(-7)-10(-6) M) and iberiotoxin (10(-7)-10(-6) M). The reversal
      potential for each current indicated that K+ channels play a major role in the
      generation of each current. Both spontaneous currents and ICAF but not ICCh were
      abolished in nominally Ca2+-free and nicardipine (10(-6) M)-containing media.
      These results suggest that the activity of L-type voltage-sensitive Ca2+ channels
      is important in the generation and maintenance of spontaneous currents and ICAF
      but not ICCh. Ryanodine (10(-6) M) prevented spontaneous currents, ICAF and
      caffeine-induced [Ca2+]i elevation but not ICCh and carbachol-induced [Ca2+]i
      elevation, suggesting that the response of bladder smooth muscle cells to
      carbachol may involve a Ca2+ store distinct from that for caffeine. Pretreatment
      with carbachol suppressed ICAF to 22 +/- 7% (n = 7) and the caffeine-induced
      [Ca2+]i elevation to 25 + 3% (n = 6). Similarly, caffeine suppressed ICCh to 23
      +/- 4% (n = 9) and the carbachol-induced [Ca2+]i elevation to 24 +/- 6% (n = 6).

PMID- 9650833
TI  - P2 receptor-mediated inhibition of adenylyl cyclase in PC12 cells.
AB  - PC12 pheochromocytoma cells have P2 receptors which are coupled to Ca2+ influx
      and catecholamine release. Previously we reported that ATP stimulated cyclic AMP
      accumulation at low concentrations up to 100 microM but showed inhibitory effects
      above this concentration [Yakushi, Y., Watanabe. A.. Murayama, T., Nomura, Y.,
      1996. Eur. J. Pharmacol. (314) 243-248]. In this study we investigated the
      characteristics of the inhibitory effects of ATP analogs. In the presence of 10
      microM forskolin, an activator of adenylyl cyclase, ATP, adenosine 5'-O-(3
      thiotriphosphate) (ATPgammaS), 2',3'-O-(4-benzoyl) benzoyl ATP, 2-methylthio ATP
      and adenosine 5'-O-(2-thiodiphosphate) inhibited cyclic AMP accumulation in a
      dose-dependent manner from 100 microM. UTP, alphabeta and betagamma-methylene ATP
      had no or very limited effects. The relative order of ATP analogs suggests that
      the ATP receptor appears to be P2Y-like. However, suramin, an antagonist of P2X
      and P2Y receptors, and reactive blue-2, which inhibited betagamma-methylene ATP
      induced cyclic AMP accumulation, did not modify the inhibitory effect of
      ATPgammaS. Treatment with pertussis toxin, which completely abolished the effect
      of carbachol, had no effect on the action of ATP over 300 microM. The existence
      of a new type of ATP receptor-mediated inhibition of adenylyl cyclase is proposed
      in PC12 cells.

PMID- 9650834
TI  - Structural significance of azaheterocyclic amines related to Parkinson's disease
      for dopamine transporter.
AB  - We have evaluated the neuronal uptake of 12 neutral and quaternary
      azaheterocyclic amines that are possible candidates for idiopathic Parkinson's
      disease via dopamine transporter of striatal synaptosomes. The double-reciprocal
      plots for dopamine transporter obtained from Wistar rat and C57BL/6 mouse
      synaptosomes with N-methyl-4-phenylpyridinium cation (MPP+) as a substrate were
      identical to each other. Neutral beta-carbolines and tetrahydroisoquinolines were
      unfavorable substrates for dopamine transporter. The quarternization of these
      compounds strikingly increased the affinity for dopamine transporter with 2-10
      times greater Km and 10 times smaller Vmax values than MPP+. Although catechol
      tetrahydroisoquinolines were weak substrates, their quarternization reduced their
      original properties as substrates for dopamine transporter. These results provide
      both topographic and electrogenic information of azaheterocyclic amines for the
      dopamine transporter-mediated influx. The intramolecular distance between the N
      atom and the centroid of the benzene ring could be an important factor for the
      recognition of binding site of dopamine transporter, and an adequate net charge
      similar to dopamine would be further required for translocation into the cells.

PMID- 9650835
TI  - Catecholaminergic CATH.a cells express predominantly delta-opioid receptors.
AB  - CATH.a cells are a catecholaminergic cell line of neuronal origin. The opioid
      receptor complement expressed by CATH.a cells was defined pharmacologically and
      by reverse transcription-polymerase chain reaction (RT-PCR). CATH.a cells were
      found to express mRNA encoding all three of the major subtypes of opioid
      receptors. The relative abundance of CATH.a cell opioid receptor transcripts was
      delta > kappa> mu. Pharmacological and functional data were in agreement with the
      results of RT-PCR inasmuch as delta-opioid receptor was identified as the most
      abundant opioid receptor subtype expressed by CATH.a cells. In addition, at least
      one of the opioid signalling pathways, inhibition of adenylyl cyclase activity,
      was found to be operant in this cell line. CATH.a cells should be of general
      utility for the study of opioid receptor signalling mechanisms in the context of
      catecholaminergic neurons.

PMID- 9650836
TI  - Vasoactive intestinal peptide modification at position 22 allows discrimination
      between receptor subtypes.
AB  - Secretin and growth hormone releasing factor (GRF) have a weak affinity for VIP
      (vasoactive intestinal peptide)/PACAP (pituitary adenylate cyclase activating
      polypeptide) receptors, but discriminate between VIP1/PACAP and VIP2/PACAP
      receptors. This previously allowed us to develop modified secretin and GRF
      derivatives as high affinity and highly selective VIP1/PACAP receptor ligands. We
      tested the hypothesis that the presence of a Gln residue at position 24 and a Leu
      residue at position 22 was responsible for their VIP1/PACAP receptor selectivity.
      [Gln24]VIP was not different from VIP but [Leu22]VIP had a 100-fold lower
      affinity for VIP2/PACAP receptors as compared to VIP1/PACAP receptors. The
      substitution of Tyr22 by Phe22 in VIP had no significant effect on the
      recognition of both receptors but [Ala22]VIP had a reduced affinity for the
      VIP2/PACAP receptor. This indicated that an aromatic residue at position 22 of
      VIP was required for a high affinity for the VIP2/PACAP receptor but not for the
      VIP1/PACAP receptor.

PMID- 9650837
TI  - Characterization and distribution of angiotensin II receptor subtypes in the
      mouse brain.
AB  - We localized and characterized angiotensin II receptor subtypes (AT1 and AT2) in
      the mouse brain, with the use of autoradiography after incubation with
      [l25I][Sar1]-angiotensin II or [125I]CGP 42112 and displacement with selective
      angiotensin AT1 (losartan and candesartan) or angiotensin AT2 (CGP 42112(1) and
      PD 123319(2)) receptor ligands. In the mouse, the receptor subtype affinity for
      the different ligands was similar to that of the rat. The receptor subtype
      distribution was also similar to that in the rat, with some notable exceptions,
      such as the presence of angiotensin AT1 but not AT2 receptors in the locus
      coeruleus, and the expression of angiotensin AT1 receptors in the caudate
      putamen. These results confirm that careful consideration of the specific
      distribution of receptor subtypes in different species, even those closely
      related such as the mouse and the rat, should be conducted before meaningful
      comparisons could be proposed. Our data also form the basis for future studies of
      mouse models such as those with angiotensin receptor gene deficiencies.

PMID- 9650838
TI  - Dose-related inversion of cinnarizine and flunarizine effects on mitochondrial
      permeability transition.
AB  - We investigated the effects of cinnarizine and flunarizine on mitochondrial
      permeability transition, ATP synthesis, membrane potential and NAD(P)H oxidation.
      Both drugs were effective in inhibiting the mitochondrial permeability transition
      induced either by Ca2+ alone or in the presence of tert-butylhydroperoxide. This
      protective effect occurred at low concentrations (< 50 microM) of these drugs and
      was accompanied by the inhibition of NAD(P)H oxidation and the restoration of the
      mitochondrial membrane potential decreased by a high concentration of Ca2+ (25
      microM). However, at higher concentrations (> 50 microM) of cinnarizine and
      flunarizine and in the absence of both tert-butylhydroperoxide and Ca2+, their
      effects on the mitochondria were reversed as follows: mitochondrial permeability
      transition was generated, mitochondrial NAD(P)H was oxidized and membrane
      potential collapsed. These deleterious effects were not antagonized by
      cyclosporine A, the most potent inhibitor of the mitochondrial permeability
      transition, but by 2,6-di-tert-butyl-4-methylphenol, a known antioxidant agent.
      This mitochondrial effect was neither accompanied by an increase in
      malondialdehyde production nor by an increase in H2O2 generation, which attested
      that the effect of both drugs was not due to an increase in reactive oxygen
      species production. The dual effects of both cinnarizine and flunarizine on
      mitochondrial functions is discussed with regard to both the protective effect
      afforded by these drugs against ischemia-reperfusion injury and their side effect
      observed in some therapeutic situations where an overdosage seems likely.

PMID- 9650839
TI  - An agonist-like monoclonal antibody against the human beta2-adrenoceptor.
AB  - Monoclonal antibodies were produced against a peptide corresponding to the second
      extracellular loop of the human beta2-adrenoceptor. One of these monoclonals,
      inducing an agonist-like effect in neonatal rat cardiomyocytes, was used to
      define the structural and physiological basis of this activity. The epitope
      recognized by the antibody corresponds to the sequence Trp-Tyr-Arg-Ala-Thr-His
      Gln-Glu as determined by peptide scanning. Analysis by alanine modification of
      the peptide epitope showed the importance of the Trp, and Glu residues in
      antibody recognition The apparent affinity of the antibody assessed either by
      surface plasmon resonance or by functional titration on its agonist-like activity
      showed a similar value (10(8) M(-1)). The antibody recognized the receptor in its
      native form as shown by immunofluorescence experiments on A431 cells but not in
      its denatured form as shown by its absence of staining in immunoblots. The
      positive chronotropic effect in vitro was specifically blocked by both the
      antigenic peptide and the specific beta2-antagonist (+/-)-1-[2,3-(Dihydro-7
      methyl1H-inden-4-yl)oxy]-3-[(1-methy lethyl)amino]-2-butanol hydrochloride
      (ICI1118,551). This activity was mediated through activation of Ca2+ L-type
      channels as assessed in guinea pig cardiomyocytes. These results suggest that the
      epitope is located in an extracellular alpha-helix, whose recognition by the
      antibody could stabilize the receptor in its 'active' conformation.

PMID- 9650840
TI  - Concomitant regulation of Ca2+ mobilization and G13 expression in human
      erythroleukemia cells.
AB  - In human erythroleukemia (HEL) cells, stimulation of alpha2-adrenoceptors by
      adrenaline or neuropeptide Y Y1 receptors by neuropeptide Y, concomitantly
      inhibit cAMP accumulation and stimulate mobilization of Ca2+ from intracellular
      stores via pertussis toxin-sensitive G-proteins. Treatment of HEL cells in
      chemically-defined, serum-free medium with 1.25% dimethylsulfoxide (DMSO) for 4
      days, increased alpha2-adrenoceptor number by 120%, while the neuropeptide Y
      receptor number was not significantly changed. In DMSO-treated HEL cells, Ca2+
      elevations by adrenaline or neuropeptide Y were significantly reduced by 28% and
      57%, respectively, while basal Ca2+ and elevations by thrombin or thapsigargin
      were not significantly altered. Adrenaline and neuropeptide Y-induced inhibition
      of forskolin-stimulated cAMP accumulation was not significantly altered upon DMSO
      treatment. While immunodetectable alpha-subunits of Gi2 were not significantly
      changed by DMSO treatment, those of Gi3 were reduced by 27%. Inactivation of
      pertussis toxin substrates by pertussis toxin treatment and inhibition of
      adrenaline or neuropeptide Y stimulated Ca2+ elevations were linearly correlated.
      These data are compatible with the idea that, in HEL cells, alpha2-adrenoceptors
      and neuropeptide Y receptors couple to inhibition of adenylyl cyclase via Gi2
      while they couple to Ca2+ elevations via Gi3.

PMID- 9650841
TI  - Potent effects of a selective cannabinoid receptor agonist on some guinea pig
      medial vestibular nucleus neurons.
AB  - Binding studies have indicated that the density of the cannabinoid CB, receptor
      is very low in the vestibular nucleus complex compared to other areas of the
      central nervous system (CNS), suggesting that CB1 receptors may have little
      functional significance for the vestibular nucleus. However, the dizziness often
      produced by cannabis suggests that the vestibular system may be implicated. We
      investigated the effects of the selective CB1 receptor agonist, CP 55940 (the
      levorotatory enantiomer of desacetyllevonantradol), on medial vestibular nucleus
      neurons in guinea pig brainstem slices in vitro. Only 3/18 medial vestibular
      nucleus neurons tested with 1 microM CP 55940 showed changes in firing rate,
      however these were decreases with an average magnitude of 72.3%; 3/4 neurons
      tested with 10 microM CP 55940 showed decreases with an average magnitude of
      92.7% (P < 0.05 in both cases). In all cases the effects of CP 55940 were long
      lasting. These results suggest that despite the low density of CB1 receptors in
      the vestibular nucleus complex, they may be of functional significance for the
      behavioural effects of cannabis use.

PMID- 9650842
TI  - Adenosine receptor activation and nociception.
AB  - Adenosine and ATP exert multiple influences on pain transmission at peripheral
      and spinal sites. At peripheral nerve terminals in rodents, adenosine A1 receptor
      activation produces antinociception by decreasing, while adenosine A1 receptor
      activation produces pronociceptive or pain enhancing properties by increasing,
      cyclic AMP levels in the sensory nerve terminal. Adenosine A3 receptor activation
      produces pain behaviours due to the release of histamine and 5-hydroxytryptamine
      from mast cells and subsequent actions on the sensory nerve terminal. In humans,
      the peripheral administration of adenosine produces pain responses resembling
      that generated under ischemic conditions and the local release of adenosine may
      contribute to ischemic pain. In the spinal cord, adenosine A receptor activation
      produces antinociceptive properties in acute nociceptive, inflammatory and
      neuropathic pain tests. This is seen at doses lower than those which produce
      motor effects. Antinociception results from the inhibition of intrinsic neurons
      by an increase in K+ conductance and presynaptic inhibition of sensory nerve
      terminals to inhibit the release of substance P and perhaps glutamate. There are
      observations suggesting some involvement of spinal adenosine A2 receptors in pain
      processing, but no data on any adenosine A3 receptor involvement. Endogenous
      adenosine systems contribute to antinociceptive properties of caffeine, opioids,
      noradrenaline, 5-hydroxytryptamine, tricyclic antidepressants and transcutaneous
      electrical nerve stimulation. Purinergic systems exhibit a significant potential
      for development as therapeutic agents. An understanding of the contribution of
      adenosine to pain processing is important for understanding how caffeine produces
      adjuvant analgesic properties in some situations, but might interfere with the
      optimal benefit to be derived from others.

PMID- 9650843
TI  - Apamin improves spatial navigation in medial septal-lesioned mice.
AB  - We investigated the effects of acute i.p. injections of the Ca2+-dependent K+
      channel blocker, apamin, on water maze spatial navigation, Y-maze and passive
      avoidance behavior in intact and medial septal-lesioned mice. Apamin 0.02, 0.06
      or 0.2 mg/kg (i.p.) administered 30 min before or immediately after the training
      did not affect the performance of intact mice. Apamin 0.02 or 0.06 mg/kg (i.p.)
      administered immediately after the daily training did not affect the performance
      of medial septal-lesioned mice. Apamin 0.02 and 0.06 mg/kg (i.p.) administered 30
      min before daily training reversed the navigation failure present in medial
      septal-lesioned mice during the initial and reversal learning stages of the water
      maze task. Apamin had no effect on the cognitive performance in Y-maze or passive
      avoidance tests. The results indicate that blockade of Ca2+-dependent K+ channels
      may facilitate acquisition of spatial navigation performance, but has no effect
      on consolidation, inhibitory avoidance and spontaneous alternation behavior in
      mice.

PMID- 9650844
TI  - The effect of oxcarbazepine on behavioural despair and learned helplessness.
AB  - The effect of oxcarbazepine was evaluated in two tests of depression (forced
      swimming and learned helplessness) and in the open-field test. Acute (three times
      over 24 h) oxcarbazepine 80 mg/kg (but not 40 mg/kg) decreased immobility time in
      the forced swimming test. In the learned helplessness test, 4 days of treatment
      with oxcarbazepine 80 mg/kg reversed the deficits induced by foot-shock in rats
      submitted to the two-way active avoidance test. Oxcarbazepine 80 mg/kg did not
      modify the behaviour of rats in the open-field test, an indication that, at this
      dose, oxcarbazepine did not show a locomotor stimulatory effect. Thus, the data
      of the present study suggest that oxcarbazepine has a potential antidepressive
      effect.

PMID- 9650845
TI  - Facilitation of cognitive functions by a specific alpha2-adrenoceptor antagonist,
      atipamezole.
AB  - The present experiments investigated the effects of a specific and potent alpha2
      adrenoceptor antagonist, atipamezole (as a stimulator of the noradrenergic
      system) on cognitive performance in rats. Atipamezole enhanced the acquisition of
      a linear-arm maze test and also improved the choice accuracy of poorly performing
      rats in a delayed (20 min) three-choice maze test. Furthermore, atipamezole
      improved the achievement of a one-trial appetite-maze when injected immediately
      after teaching, thus having an effect on consolidation. Atipamezole clearly
      impaired the acquisition of the active avoidance test. The present results
      indicate that stimulation of noradrenergic system by atipamezole improves the
      performance of animals in tasks assessing relational learning and memory,
      possibly affecting attention, short-term memory and the speed of information
      processing. It has also an effect on a consolidation process unrelated to
      attentional or motivational mechanisms. In a stressful test. stimulation of
      noradrenaline release leads to impairment of performance.

PMID- 9650846
TI  - Effects of WAY 100635 and (-)-5-Me-8-OH-DPAT, a novel 5-HT1A receptor antagonist,
      on 8-OH-DPAT responses.
AB  - The neurochemical profile at both post and presynaptic 5-HT1A receptors of a
      novel 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) analog, 5-methyl-8
      hydroxy-2-(di-n-propylamino)tetralin ?(+/-)-5-Me-8-OH-DPAT? and its stereoisomers
      was determined and compared to that of the highly selective 5-HT1A receptor
      antagonist, N-[4-(2-methoxyphenyl)-1-piperazinyl]-N-(2-pyridinyl) cyclo
      hexanecarboxamide (WAY 100635). We evaluated their effects on 8-OH-DPAT-induced
      decrease in cAMP production, on 8-OH-DPAT-induced decrease in rat ventral
      hippocampal extracellular 5-hydroxytryptamine (5-HText) levels and in body
      temperature in mice. Both (+/-)- and (-)-5-Me-8-OH-DPAT blocked the 8-OH-DPAT
      induced inhibition of forskolin-stimulated cAMP production. Moreover, while
      having no significant effect when injected alone, (+/-)-, (-)-5-Me-8-OH-DPAT and
      WAY 100635 antagonized the 8-OH-DPAT-induced decrease in 5-HText in rats and
      hypothermia in mice. By contrast, the (+) isomer inhibited the cAMP synthesis and
      did not modify the 8-OH-DPAT response on 5-HText in ventral hippocampus. These
      data suggest that (+/-)-5-Me-8-OH-DPAT acts selectively, its activity residing in
      the (-) enantiomer, this latter compound acting similarly to WAY 100635 as a
      full, selective and silent 5-HT1A antagonist.

PMID- 9650847
TI  - 5-Hydroxytryptophan-induced myoclonus in guinea pigs: mediation through 5-HT1/2
      receptor subtypes.
AB  - In guinea pigs, myoclonus can be induced by 5-hydroxytryptamine (5-HT, serotonin)
      precursors and synthetic 5-HT receptor agonists, yet the receptor subtype
      specificity of this behavior is not fully delineated. Guinea pigs were pre
      treated with carbidopa (50 mg) followed by one of eight 5-HT antagonists: (-)-N
      tert-butyl-3-[4-(2-methoxyphenyl) piperazin-1-yl]-2-phenyl propionamide ((-)-WAY
      100135) (5-HT1A), N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethyl]-N-(2-pyridyl)
      cy clohexancarboxamide (WAY 100635) (5-HT1A), methiothepin mesylate (5-HT1/2),
      mesulergine hydrochloride (5-HT2A/2C), N[4-methoxy-3-(4-methyl-L
      piperazinyl)phenyl]-2'-methyl-4'-(5-methyl-1,2 ,4-oxadizol-3-yl) (GR 127935) (5
      HT1D), trans-4-[(3Z)3-(2-dimethylaminoethyl)oxyimino-3(2-fluorop hen yl) propen-1
      yl]phenol, hemifumarate (SR 46349) (5-HT2), ondansetron hydrochloride (5-HT3),
      and [1-[2-[methylsulphonyl)amino]ethyl]-4-piperidinyl]methyl-5-fluoro-2-meth oxy
      1H-indole-3-carboxylate (GR 125487) (5-HT4). Thirty minutes later, they received
      5-hydroxytryptophan (5-HTP) (75 mg/kg, sc) and myoclonic jumping rates were
      assessed every 10 min for 200 min by a blinded observer. Repeated measures
      analysis of variance of drug-induced antagonism of 5-HTP-induced myoclonus
      revealed a significant effect for the 5-HT receptor antagonists methiothepin
      mesylate, GR127935, and mesulergine hydrochloride compared to placebo, and each
      of these drugs inhibited 5-HTP-induced myoclonus in a dose-dependent fashion.
      Based on the receptor profiles of the three effective antagonists, 5-HTP-induced
      myoclonus is influenced by the 5-HT1/2 receptor systems. The absence of a
      significant change with any other receptor subtype antagonist suggests that
      myoclonus is not related to diffuse activation of central serotonergic
      mechanisms.

PMID- 9650848
TI  - Pharmacologic restoration of suppressed temperature rhythms in rats by melatonin,
      melatonin receptor agonist, S20242, or 8-OH-DPAT.
AB  - Endogenous circadian rhythms in body temperature and locomotor activity rhythms
      are suppressed in Sprague-Dawley rats exposed to prolonged continuous light,
      possibly as a result of a profound alteration of the melatonin secretion rhythm.
      The ability to restore circadian system function with either exogenous melatonin,
      or melatonin receptor agonist S20242 (N-[2-(7-methoxy napth-1-yl)ethyl]
      propionamide), or 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin
      (8-OH-DPAT), was investigated under these conditions. Seven rats received a daily
      6-h intravenous infusion of melatonin (0.01 mg kg(-1)) for 10 days, which
      generates a nearly physiological circadian rhythm of urinary 6-sulfatoxy
      melatonin, the main urinary metabolite of melatonin. Nevertheless, there was no
      effect on body temperature or locomotor activity rhythms. Then, 49 rats received
      daily subcutaneous melatonin (0.01, 1 or 5 mg kg(-1) day(-1)), S20242 (1 or 5 mg
      kg(-1) day(-1)) or 8-OH-DPAT (5 mg kg(-1) day(-1)) for 30 days. The circadian
      rhythm in body temperature was restored by subcutaneous melatonin or by S20242 as
      a function of the dose or by 8-OH-DPAT. The effect started within the first 10
      days of treatment and persisted for I to 3 weeks following the end of treatment
      in 8 of 10 rats receiving melatonin, in 9 of 11 rats treated with S20242 and in 1
      of 4 rats treated with 8-OH-DPAT. Activity was less susceptible to entrainment
      than temperature with these drugs, since circadian rhythmicity was restored in
      only 2 of 6 rats treated with melatonin and in 1 of 4 rats treated with 8-OH
      DPAT. These data demonstrate a specific action of subcutaneous melatonin, S20242
      or 8-OH-DPAT on temperature rather than on activity rhythms. This differential
      effect on two major outputs of the suprachiasmatic nucleus further supports the
      existence of two independent oscillators in this hypothalamic circadian clock,
      which may be considered as separate pharmacological targets in the circadian
      system.

PMID- 9650849
TI  - Dexamethasone augments ischemia-induced extracellular accumulation of glutamate
      in gerbil hippocampus.
AB  - Glucocorticoids exacerbate neuronal damage due to hypoxia, ischemia, seizure and
      hypoglycemia. Because the release of glutamate is closely involved in neuronal
      damage, the effects of dexamethasone on the ischemia-induced accumulation of
      extracellular amino acids (aspartate, glutamate, and glycine) were investigated
      in the gerbil hippocampal CA1 region by a microdialysis-high-performance liquid
      chromatography procedure in vivo. There were no differences in the extracellular
      concentrations of amino acids before ischemia between the control group and the
      dexamethasone (3m microg, i.c.v.)-injected group. The concentration of glutamate
      reached 246% of that before ischemia within 2.5 min of transient forebrain
      ischemia. Dexamethasone augmented the increase in glutamate to 508% of that
      before ischemia. This finding suggests that glucocorticoids aggravate ischemic
      neuronal damage by causing glutamate to accumulate in the extracellular space.

PMID- 9650850
TI  - Depressor responses to endothelin-1 into the superior colliculus of rats:
      predominant role of endothelin ET(B) receptors.
AB  - We used in vitro autoradiography to identify the endothelin-1 receptor subtype(s)
      in the superficial gray layer of the superior colliculus of rats. These studies
      showed dense binding of (3-[125I]iodotyrosyl13)-[Ala11,15]Ac-endothelin-1-(6-2 1)
      (BQ3020) (for endothelin ETB receptors), while tissues incubated with [125I]( N
      (hexahydro-1-azepinyl)carbonyl)L-Leu(1-Me)D-Trp-D-Tyr (PD151242) (for endothelin
      ETA receptors) had low binding. In addition, we examined the effects of the
      endothelin receptor antagonists, (R)-2-[(R)-2-[(S)-2-[[1-hexahydro-1H
      azepinyl)]carbonyl]amino-4-++ +methylpentanoyl]-amino-3-(2-pyridyl)propionic acid
      (FR139317) (endothelin ETA receptor-selective), (+)-(1S,2R,3S)-3-(2
      carboxymethoxy-4-methoxyphenyl)-1-(3,4-methylenediox yphenyl)-5-(prop-1
      yloxy)indane-2-carboxylic acid (SB209670) (endothelin ETA/ETB receptor non
      selective) and N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma-metLeu-D-1-m
      ethoxycarbonylTrp-D-Nle (BQ-788) (endothelin ETB receptor-selective antagonist)
      on the responses following administration of endothelin-1 into the superficial
      layer of the superior colliculus. Endothelin-1 microinjected into this nucleus
      causes decreases in blood pressure (control, 109 +/- 6 mmHg, n = 6; endothelin-1,
      72 +/- 5 mmHg, n = 6). These effects were greatly reduced by pre-administration
      into the superior colliculus of BQ-788 (5 nmol/rat) or SB209670 (3 nmol/rat) (94
      +/- 5 and 98 +/- 6%, respectively) but were not affected by FR139317 (5 nmol/rat)
      (6 +/- 3%). Therefore, together with autoradiography, our functional data showed
      that endothelin ETB receptors are the predominant mediators of depressor
      responses induced by endothelin-1 injected into the superior colliculus of the
      rat.

PMID- 9650851
TI  - Effect of the gastrin-releasing peptide antagonist BIM 26226 and lanreotide on an
      acinar pancreatic carcinoma.
AB  - The effects of a potent specific gastrin-releasing peptide receptor antagonist,
      BIM 26226 ([D-F5 Phe6, D-Ala11] bombesin (6-13) OMe), and the long-acting
      somatostatin analogue, lanreotide (BIM 23014), on the growth of an acinar
      pancreatic adenocarcinoma growing in the rat or cultured in vitro were
      investigated. Lewis rats bearing a pancreatic carcinoma transplanted s.c. in the
      scapular region, were treated with gastrin-releasing peptide (30 microg/kg per
      day), BIM 26226 (30 and 100 microg/kg per day) and lanreotide (100 microg/kg per
      day) alone or in combination for 14 successive days. Chronic administration of
      BIM 26226 and lanreotide significantly inhibited the growth of pancreatic tumours
      stimulated or not by gastrin-releasing peptide (GRP), as shown by a reduction in
      tumour volume, protein, ribonucleic acid, amylase and chymotrypsin contents. This
      effect was more pronounced with 100 microg/kg per day BIM 26226 than with 30
      microg/kg per day. However, BIM 26226 and lanreotide, given together, did not
      exert any additive effect on GRP-treated and -untreated tumours. In cell
      cultures, both BIM 26226 and lanreotide (10(-6) M) inhibited [3H]thymidine
      incorporation in tumour cells induced or not by GRP, but no increased effect was
      observed after combined treatment with both agents. Binding studies showed that
      BIM 26226 had a high affinity for GRP receptors in tumour cell membranes (IC50 =
      6 nM). These results from in vivo and in vitro experiments suggest that BIM 26226
      and lanreotide are able to reduce the growth of an experimental acinar pancreatic
      tumour. Thus, these agents represent interesting steps toward the development of
      new approaches for treatment of pancreatic carcinomas.

PMID- 9650852
TI  - Comparison of cyclooxygenase-1 and -2 inhibitory activities of various
      nonsteroidal anti-inflammatory drugs using human platelets and synovial cells.
AB  - Recent studies have shown that cyclooxygenase exists in two isozyme forms. Since
      differences in the pharmacological profiles of nonsteroidal anti-inflammatory
      drugs (NSAIDs) might be accounted for by varying degrees of selectivity for these
      isozymes, cyclooxygenase-1 and -2, the relative potency of various NSAIDs in
      inhibiting their activities was examined in intact human cells. We used human
      platelets cyclooxygenase-1 and interleukin-1beta-stimulated human synovial cell
      cyclooxygenase-2 for measuring cyclooxygenase selectivity. The presence of the
      enzymes was confirmed by immunoblotting and immunoprecipitation analysis, and by
      the reverse transcriptase-polymerase chain reaction. Mean IC50 values (microM)
      for human platelet cyclooxygenase-1 and interleukin-1beta-stimulated human
      synovial cell cyclooxygenase-2 and cyclooxygenase-1/-2 IC50 ratio of various
      NSAIDs were as follows: aspirin, 3.2, 26, 0.12; diclofenac, 0.037, 0.00097, 38;
      etodolac, 122, 0.68, 179; ibuprofen, 3.0, 3.5, 0.86; indomethacin, 0.013, 0.044,
      0.30; loxoprofen (active metabolite), 0.38, 0.12, 3.2; NS-398, 12, 0.0095, 1263;
      oxaprozin, 2.2, 36, 0.061; zaltoprofen, 1.3, 0.34, 3.8; respectively. Our
      bioassay system employing intact human cells to assess the cyclooxygenase
      selectivity of NSAIDs may provide clinically useful information.

PMID- 9650853
TI  - Immunologic action of [Met5]enkephalin fragments.
AB  - The aim of this study was to evaluate the effects of [Met5]enkephalin, des-Met
      [Met5]enkephalin, des-Tyr-[Met5]enkephalin, and Tyr-Gly-Gly on natural killer
      cytotoxic activity and on concanavalin A- and lipopolysaccharide-stimulated
      proliferation of B and T cells in mice. Single i.p. injections of
      [Met5]enkephalin, des-Met-[Met5]enkephalin, and Tyr-Gly-Gly increased both
      natural killer cytotoxicity and proliferation of mitogen-stimulated B and T
      cells. These effects were inhibited by naloxone pretreatment, which suggests the
      opioid mechanism of the peptides studied. The rate of lymphocytic proliferation
      increases not only after single injection of [Met5]enkephalin or its metabolites,
      but also after 3 or 7 days of treatment. Apart from the functional effects,
      [Met5]enkephalin, des-Met-[Met5]enkephalin, and Tyr-Gly-Gly increased the
      percentages of natural killer cells and T cells. The results of this study
      suggest that the immunomodulatory action of [Met5]enkephalin may be mediated or
      enhanced by its N-terminal metabolites des-Met-[Met5]enkephalin and Tyr-Gly-Gly.

PMID- 9650854
TI  - Inhibition of nociceptin on sensory neuropeptide release and mast cell-mediated
      plasma extravasation in rats.
AB  - Nociceptin (20 microg/kg i.p.) strongly inhibited cutaneous Evans blue
      accumulation in the chronically denervated hindpaw of the rat in response to mast
      cell degranulating peptide (MCDP, 0.25 microg in 100 microl) but it had no and
      marginal effect on plasma extravasation induced by 5-hydroxytryptamine (5-HT, 0.5
      microg in 100 microl) and histamine (0.1 microg in 100 microl), respectively.
      Release of sensory neuropeptides such as substance P, calcitonin gene-related
      peptide (CGRP) and somatostatin from the rat isolated trachea in response to
      capsaicin (10(-8) M) or bradykinin (10(-7) M) were also attenuated by nociceptin
      (100 and 300 nM). It is concluded that chemically induced discharge of mediators
      from mast cells and from capsaicin-sensitive afferent nerve terminals are both
      inhibited by nociceptin that participates in the anti-inflammatory effect of the
      peptide.

PMID- 9650855
TI  - Buprenorphine hydrochloride induces apoptosis in NG108-15 nerve cells.
AB  - A morphine alkaloid derivative, buprenorphine hydrochloride, induces apoptosis in
      NG108-15 cells. Apoptosis was detected mainly by apoptosis-specific DNA
      fragmentation and morphological changes. This apoptosis was dose-dependent and
      the time-course experiment indicated that DNA fragmentation occurred within 4 h
      after administration of buprenorphine hydrochloride. Specific inhibitors of the
      previously characterized apoptotic signal cascade as well as antagonists for
      opioid receptors were tested. Zn2+, herbimycin A, caspase inhibitors YVAD (Ac-Tyr
      Val-Ala-Asp-CHO) and DEVD (Ac-Asp-Glu-Val-Asp-CHO), naloxone and naltrindole had
      no effect on apoptosis-specific DNA fragmentation. The serine protease inhibitor
      TPCK (N-tosyl-L-phenylalanyl chloromethyl ketone) specifically inhibited
      apoptosis-specific DNA fragmentation induced by buprenorphine hydrochloride;
      however, cell viability measurements revealed that cell death still occurred in
      NG108-15 cells. Thus TPCK pretreatment before buprenorphine hydrochloride
      administration induced apoptosis-independent cell death, presumably necrosis, in
      NG108-15 cells. This suggests that an unidentified serine protease, presumably
      functioning in the buprenorphine hydrochloride-specific death-signal cascade,
      could be pivotal for the rapid apoptosis observed in NG108-15 cells upon
      treatment with buprenorphine hydrochloride.

PMID- 9650856
TI  - Functional interactions of L-162,313 with angiotensin II receptor subtypes and
      mutants.
AB  - A nonpeptide ligand, L-162,313 (5,7-dimethyl-2-ethyl-3-[[4-[2(n
      butyloxycarbonylsulfonamido)-5-is obutyl-3
      thienyl]phenyl]methyl]imidazo[4,5,6]pyridine) was characterized on the
      angiotensin II receptors. This compound displaced [125I][Sar1]angiotensin II from
      rat angiotensin AT1A, AT1B or AT2 receptor individually expressed in COS-7 cells
      (Ki = 207 nM, 226 nM and 276 nM, respectively). In monkey kidney cells expressing
      angiotensin AT1A or AT1B receptors, it stimulated inositol phosphate
      accumulation, but the maximal response was 34.9 and 23.3%, respectively, of those
      of angiotensin II. Furthermore, an antagonist effect of L-162.313 was observed in
      response to angiotensin II. Single-point substitutions in the second and third
      transmembrane domains of the rat angiotensin AT1A receptor, which impaired the
      binding of losartan (2-n-butyl-4-chloro-5-hydroxymethyl-1[(1H-tetrazol-5
      yl)biphenyl-4 -yl)methyl]imidazole), also affected the binding of L-162,313.
      Losartan and L-162,313 require some common structural determinants for non
      peptide recognition on the angiotensin AT1 receptor. Furthermore, some of these
      substitutions, which impaired the inositol phosphate accumulation in response to
      angiotensin II, also impaired the response to L-162,313. Angiotensin II and L
      162,313 require common critical residues for angiotensin AT1 receptor activation.

PMID- 9650857
TI  - The electrophysiological effects of tetraphenylphosphonium on vascular smooth
      muscle.
AB  - The effect of the lipophilic quaternary ion, tetraphenylphosphonium, on membrane
      potential of segments of rat small mesenteric artery and on the current in single
      voltage-clamped smooth muscle cells from rabbit portal vein was studied. In rat
      small mesenteric artery, tetraphenylphosphonium (1-30 microM) caused membrane
      depolarization of approximately 23 mV and decreased or abolished the
      hyperpolarization induced by the KATP channel opener, levcromakalim (0.1-3
      microM). In rabbit portal vein K+ currents induced by levcromakalim (10 microM)
      or pinacidil (10 microM) were completely inhibited by tetraphenylphosphonium
      (IC50 0.5 microM). The results show that tetraphenylphosphonium antagonizes the
      KATP current induced by K+ channel openers in vascular smooth muscle possibly by
      acting on the KATP channel itself.

PMID- 9650858
TI  - Alpha1-adrenoreceptor stimulation causes vascular smooth muscle cell hypertrophy:
      a possible role for isoprenoid intermediates.
AB  - We investigated whether contraction-induced agonists such as alpha1-adrenoceptor
      agonists are important regulators of smooth muscle cell hypertrophy by examining
      the effects of one potent agonists, phenylephrine, on the hypertrophy. Under the
      experimental conditions used, we found that phenylephrine was potent in inducing
      alpha1-adrenoreceptor-dependent hypertrophy of vascular smooth muscle cells as
      defined by increased incorporation of [14C]leucine in a dose-dependent fashion.
      Further, we assessed the effect of lovastatin, an 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase inhibitor, on hypertrophy of cultured vascular
      smooth muscle cells as defined by the increased incorporation of [14C]leucine
      caused by phenylephrine. Lovastatin (5-15 microM) caused a significant dose
      dependent reduction in [14C]leucine incorporation which was completely prevented
      in the presence of exogenous mevalonate (100 microM). Exogenous low density
      lipoprotein (100 microg/ml) and cholesterol (15 microg/ml) did not prevent
      lovastatin inhibition of [14C]leucine incorporation. In contrast, the isoprenoid
      farnesol largely prevented inhibition of [14C]leucine incorporation by the
      lovastatin. We conclude that mevalonate metabolites are essential for
      phenylephrine-induced smooth muscle cell hypertrophy, possibly through the
      production of the isoprenoid farnesol.

PMID- 9650860
TI  - An asparagine residue regulating conductance through P2X2 receptor/channels.
AB  - Single channel currents were recorded from Xenopus oocytes expressing wild-type
      and mutated P2X2 receptors. When 100 mM Na+ was used as the permeant cation,
      unitary currents of about 80 pS were recorded from the oocyte expressing the wild
      type channels. The single channel conductance was roughly halved when Asn333 was
      replaced by Ile (N333I). A similar decrease in single channel currents was also
      observed when 100 mM Li+ or Cs+ was used as the permeant cation. With two other
      mutants, in which Asp315 was replaced by Val (D315V) or Tyr330 was replaced by
      lie (T333I), single channel conductance was almost the same as that of the wild
      type channels. The results suggest that Asn333, which is believed to be involved
      in the channel pore, plays an essential role in ion transport through P2X2
      receptor/channels.

PMID- 9650859
TI  - Up-regulation of human alpha7 nicotinic receptors by chronic treatment with
      activator and antagonist ligands.
AB  - This study examined the binding and functional properties of human alpha7
      neuronal nicotinic acetylcholine receptors stably expressed in human embryonic
      kidney (HEK) 293 cells following chronic treatment with nicotinic receptor
      ligands. Treatment of cells with (-)-nicotine (100 microM) for 120 h increased
      the Bmax values of [125I]alpha-bungarotoxin binding 2.5-fold over untreated
      cells. This effect was concentration-dependent (EC50) = 970 microM) and a 6-fold
      upregulation was observed with the maximal concentration of (-)-nicotine tested.
      Also, treatment of cells with ligands of varying intrinsic activities including
      (+/-)-epibatidine, (2,4)-dimethoxybenzylidene anabaseine (GTS-21) and 1,1
      dimethyl-4-phenyl piperazinium iodide (DMPP) also upregulated [125I]alpha
      bungarotoxin binding. A concentration-dependent upregulation of binding sites was
      also observed following treatment with the alpha7 nicotinic receptor antagonist,
      methyllycaconitine (EC50 = 92 microM) with a maximal upregulation of about 7
      fold. Functionally, the peak amplitude of the whole-cell currents recorded by
      fast application of (-)-nicotine after chronic treatment of cells with
      concentrations of (-)-nicotine (1000 microM) or methyllycaconitine (10 microM)
      that elicited similar increases in binding levels (3.5-fold) resulted in
      increases of 2-fold (505 +/- 21 pA) and 6-fold (1820 +/- 137 pA) respectively in
      whole cell current amplitude compared to untreated cells (267 +/- 24 pA). These
      studies clearly demonstrate that long-term exposure to both activator and
      antagonist ligands can increase the density of alpha7 nicotinic receptors and can
      differentially enhance nicotinic receptor function.

PMID- 9650861
TI  - Immunochemical characterization of in vitro culture-derived antigens of Babesia
      bovis and Babesia bigemina.
AB  - Cross-reactivity between Babesia bovis and B. bigemina becomes a problem in
      discrimination of the two infections in endemic areas where the two species
      usually occur in association. With the aim of identifying candidate proteins for
      use as specific diagnostic tools, culture-derived components of three
      geographically different stocks of B. bovis (Lismore, Kwanyanga and Mexico) and
      one of B. bigemina (Mexico) were analyzed by immunoprecipitation using acrylamide
      gel electrophoresis. The approach taken was based on the analysis of 35S
      methionine-labelled parasite antigens released into culture supernatant. A
      variety of serum samples were tested, including a panel of calf sera
      experimentally produced against the different stocks of Babesia, serum samples
      from cattle naturally infected in the field in Brazil, and a panel of anti-B.
      bovis monoclonal antibodies, previously characterized by the indirect fluorescent
      antibody test, ELISA and Western immuno-blotting. Approximately 28 and 23 bands
      (with molecular weights ranging from 200 to 14 kDa) were detected in total
      protein profiles of B. bovis and B. bigemina culture supernatants, respectively,
      whereas no bands were seen in the uninfected red blood cell culture supernatant
      (negative control). The immunoprecipitation analysis showed antigenic diversity
      amongst the stocks of B. bovis and resulted in identification of at least five B.
      bovis specific antigens common to the three stocks (molecular weights of 80, 72,
      58, 38 and 24 kDa) and four B. bigemina specific antigens (molecular weights of
      240, 112, 50 and 29 kDa).

PMID- 9650862
TI  - Seroprevalence of Babesia equi among horses in Israel using competitive
      inhibition ELISA and IFA assays.
AB  - Sera from 361 horses were tested by indirect immunofluorescence antibody test
      (IFA) and by competitive inhibition ELISA (cELISA), to detect antibodies to
      Babesia equi. The concordance between the assays was 95.7%. Application of a
      cutoff based on a calculated percent inhibition of < 20% gave a total of 22
      discrepant results, while only 8 sera negative by the cELISA were found positive
      by the IFA when a cutoff of > 20% inhibition was used. Approximately one-third of
      all the horses tested were found serologically positive to B. equi, with more
      horses testing positive from northern Israel. Among horses raised with access to
      pasture there was a significant difference in the percentage of seropositive
      reactors (76.6% in the north and 20.1% in the central region), compared with
      horses without access to pasture (14.3 and 10.3%, respectively). Nineteen percent
      of stallions were found to be positive, which was significantly less than the
      proportions of seropositive mares and geldings: 38 and 42%, respectively. No
      significant association was found between the mean age of horses and
      seroreactivity to B. equi.

PMID- 9650863
TI  - Coccidiosis in goats in the Czech Republic.
AB  - An observational study was conducted to determine coccidial infections in goats
      of 13 farms in the Czech Republic. The prevalence of oocysts of Eimeria species
      in kids (less than 3 months old), weaned but not served goats (from 3 months to 1
      year), and adult goats (1 year or more) was determined. Nine Eimeria species were
      identified in fecal samples by Sheather's sugar flotation technique. The overall
      prevalence of Eimeria oocysts in fecal specimens was 92.2%. Eimeria arloingi was
      the most common species with an overall prevalence of 84%, followed by E. hirci
      (63%) and E. ninakohlyakimovae (56%). Other species present were E. christenseni
      (55%), E. alijevi (36%), E. caprina (25%), E. aspheronica (12%), E. capriovina
      (6%) and E. jolchijevi (2%). Two or more Eimeria species were detected in 88% of
      the samples. The most prevalent species in kids was E. arloingi, while in weaned
      but not served and adult goats E. ninakohlyakimovae was the most frequently
      found. The number of oocysts excreted was generally lower in adult goats
      (2567.3+/-12678 OPG), whereas higher number oocyst per gram of feces (OPG) were
      found in kids (18565+/-24888 OPG). Clinical coccidiosis was detected in two
      farms, and E. arloingi and E. ninakohlyakimovae were implicated as its cause.
      Disease was observed in kids 2 to 4 weeks after weaning and watery feces with
      clumps of mucus, and color changes from brown to yellow or dark tarry, weight
      loss, and dehydration were the most conspicuous clinical signs. At necropsy,
      macroscopic changes included mucosal hemorrhages and whitish nodular polyps in
      the jejunum were found. Histopathological changes were characterized by local
      hypertrophy and hyperplasia of intestinal villi, villus blunting and inflammatory
      infiltration in the lamina propria. Numerous developmental stages of the
      parasites were observed in enterocytes and lacteals of intestinal villi.

PMID- 9650864
TI  - Improved detection of circulating antigen in cattle infected with Taenia saginata
      metacestodes.
AB  - In order to improve the sensitivity and the specificity of an existing IgM
      monoclonal antibody-based ELISA (Brandt et al., 1992) for the detection of
      circulating antigen in the sera of cattle infected with T. saginata metacestodes,
      a modified sandwich ELISA was developed. Monoclonal antibodies (MAbs) of the IgG
      isotype were produced against the excretory-secretory (ES)-products of T.
      saginata metacestodes. Since it was shown that the affinity of these IgG MAbs for
      ES antigen was higher than that of the IgM MAbs, the latter were replaced by two
      IgG1 MAbs (158C11 and 60H8). Furthermore, heat treatment of the sera
      significantly increased the OD-values of ES-spiked serum samples as compared to
      nontreated samples. It also decreased the number of false positive reactions.
      When the original IgM MAb-based ELISA was compared with the IgG MAb-based ELISA
      using heat treated sera from animals harbouring more than 50 living metacestodes
      of T. saginata, the sensitivity increased from 56% with the former to 92% with
      the latter assay. Only a small percentage of animals carrying less than 50 cysts
      were detected both with the ELISA using IgG or IgM MAbs. The specificity of the
      IgM- and IgG MAb-based ELISAs was 93.4% and 98.7% respectively.

PMID- 9650865
TI  - Comparative analysis of two methods used to show interspecific associations in
      naturally acquired parasite nematode communities from the abomasum of ewes.
AB  - The aim of our study was to compare a multivariate and a univariate method to
      evaluate the associations between nematode species in natural infections. We used
      a data set based on the 3-year study of the community of abomasal nematodes in
      ewes of the middle-Atlas region of Morocco. Frequency data (percentage of each
      species in the individual host community) were processed by principal component
      analysis. Euclidean distances between species (D2) were calculated from
      projections of principal component analysis on three axes and compared to a
      bivariate estimate (1 - correlation coefficient R). Low distances were recorded
      between morphs of the same species (Teladorsagia circumcincta and T. trifurcata,
      for example), which indicates a positive association. Only two species,
      Trichostrongylus axei and T. circumcincta, were negatively associated having D2
      values much over 1. The distances D2, i.e., multivariate measure of association
      intensity were similar in most cases to 1- R estimates, indicating probably the
      absence of strong multispecies association. The D2 fitted a Motomura geometric
      progression model indicating that associations were arranged in a continuum from
      low to high values, but they did not depart much from what could be expected from
      random associations for most species. The D2 interest is mostly to relate
      associations with environmental variables, and comparing with 1 - R, to assess
      the degree of interaction in the community.

PMID- 9650866
TI  - Effects of preventive anthelmintic treatment on acquired resistance to
      gastrointestinal nematodes in naturally infected cattle.
AB  - The objective of this study was to investigate the influence of different types
      of chemoprophylaxis in first season grazing calves on their resistance against a
      natural reinfection with Ostertagia ostertagi and Cooperia oncophora in the
      second grazing season. Thirty helminth-naive crossbred calves were randomly
      divided in three groups of 10 animals. The animals of group B received an
      ivermectin sustained release bolus on day 0. The calves of group D were treated
      on days 0 and 56 with a subcutaneous injection of doramectin (0.2 mg kg(-1) BW).
      Group C was the untreated control group ('immune' controls). Although exposure to
      gastrointestinal nematodes in the first grazing season was only limited, the
      chemoprophylactic treatments in groups B and D resulted in three distinctly
      different infection levels (group C > group D > group B). At the start of the
      second grazing season, six helminth-naive steers (group N, 'susceptible'
      controls) were turned out together with the second season animals. After 3 weeks
      of grazing, the 'susceptible' controls were slaughtered, together with four
      animals from each other group. Parasitological and immunological parameters
      indicated that resistance to reinfection with Ostertagia was reduced in the
      chemoprophylactic treated animals, and was negatively related to the degree of
      suppression of host-parasite contact in the first grazing season (group C > group
      D > group B > group N). None of the groups had developed a complete resistance
      against Cooperia yet. A negative relationship was observed between reduction of
      first grazing season exposure, and weight gains early in the second grazing
      season. The remaining animals stayed on pasture until the beginning of November.
      At the end of the second grazing season, levels of acquired resistance against
      Ostertagia infection were similar in all groups, and all animals had become
      immune against Cooperia. No effect of first year chemoprophylaxis on total weight
      gains could be demonstrated. Because of discrepancy between pasture larval counts
      and tracer worm counts, it was not possible to draw firm conclusions on the
      effect of chemoprophylaxis on pasture infestation levels in the second year.

PMID- 9650867
TI  - Intestinal parasites in swine in the Nordic countries: prevalence and
      geographical distribution.
AB  - In Denmark (DK), Finland (FIN), Iceland (I), Norway (N), and Sweden (S), 516
      swine herds were randomly selected in 1986-1988. Individual faecal analyses
      (mean: 27.9 per herd) from eight age categories of swine showed that Ascaris
      suum, Oesophagostomum spp., Isospora suis, and Eimeria spp. were common, while
      Trichuris suis and Strongyloides ransomi-like eggs occurred sporadically. Large
      fatteners and gilts were most frequently infected with A. suum with maximum
      prevalences of 25-35% in DK, N and S, 13% in I and 5% in FIN. With the exception
      of the remarkably low A. suum prevalence rates in FIN, no clear national
      differences were observed. Oesophagostomum spp. were most prevalent in adult pigs
      in the southern regions (21-43% in DK and southern S), less common in the
      northern regions (4-17% adult pigs infected), and not recorded in I. I. suis was
      common in piglets in DK, I, and S (20-32%), while < 1% and 5% were infected in N
      and FIN, respectively. Eimeria spp. had the highest prevalences in adult pigs
      (max. 9%) without clear geographical differences. I. suis and Eimeria spp. were
      recorded for the first time in I, and I. suis for the first time in N.

PMID- 9650868
TI  - The control of the free-living stages of Strongyloides papillosus by the
      nematophagous fungus, Arthrobotrys oligospora.
AB  - Two laboratory trials were conducted to determine the effect of the addition of
      spores (conidia) of the nematophagous fungus, Arthrobotrys oligospora, on the
      development of the ruminant parasite, Strongyloides papillosus, in cultures of
      bovine faeces. Both studies showed that at a concentration of 2000 conidia/g
      faeces virtually eliminated infective larvae (> 99% reduction), following 14 days
      incubation under ideal conditions (25 degrees C and saturated humidity) for free
      living development of this parasite species. In one trial, a high level of
      control was also observed at a 10-fold decrease in conidia concentration (200
      spores/g faeces). This work has demonstrated, in principle, that A. oligospora
      could provide a practical biological control agent against S. papillosus
      infecting intensively raised young ruminants in the humid tropics/subtropics.

PMID- 9650869
TI  - Subgingival microbiota in healthy, well-maintained elder and periodontitis
      subjects.
AB  - This investigation compared the site prevalence of 40 subgingival species in 30
      periodontally healthy (mean age 36+/-9 years), 35 elders with a well-maintained
      periodontium (mean age 77+/-5) and 138 adult periodontitis subjects (mean age
      46+/-11). Subgingival plaque samples were taken from the mesial aspect of each
      tooth (up to 28 samples) in the 203 subjects at baseline. The presence and levels
      of 40 subgingival taxa were determined in 5003 plaque samples using whole genomic
      DNA probes and checkerboard DNA-DNA hybridization. Clinical assessments including
      dichotomous measures of gingival redness, bleeding on probing, plaque
      accumulation and suppuration, as well as duplicate measures of pocket depth and
      attachment level, were made at 6 sites per tooth. The % of sites colonized by
      each species (prevalence) was computed for each subject. Differences in
      prevalence and levels among groups were sought using the Kruskal-Wallis test.
      Commonly detected species, such as Actinomyces naeslundii genospecies 2,
      Streptococcus sanguis and Streptococcus oralis did not differ significantly among
      subject groups. After adjusting for multiple comparisons, 4 species were
      significantly elevated and at greater prevalence in the periodontitis group. Mean
      % of sites (+/-SEM) colonized by Bacteroides forsythus was 10+/-3, 12+/-2 and
      40+/-2 (p<0.001) for healthy, elder and periodontitis groups respectively. The
      odds ratio was 14.4:1 that a subject had periodontitis when B. forsythus was
      detected at > or = 5% of sampled sites. Mean prevalence for Porphyromonas
      gingivalis in healthy, elder and periodontitis subjects was 4+/-2, 5+/-2 and 23+/
      2 respectively (p<0.001); for Treponema denticola 12+/-4, 10+/-3 and 30+/-2
      (p<0.001) and for Selenomonas noxia 6+/-2, 7+/-2 and 19+/-2 (p<0.01). Similar
      differences among subject groups were observed when only sites with PD 0-4 mm
      were analyzed. The data suggest an etiologic role for B. forsythus, P.
      gingivalis, T. denticola and S. noxia in adult periodontitis.

PMID- 9650870
TI  - The use of metronidazole and amoxicillin in the treatment of advanced periodontal
      disease. A prospective, controlled clinical trial.
AB  - The present clinical trial was performed to study the effect of systemic
      administration of metronidazole and amoxicillin as an adjunct to mechanical
      therapy in patients with advanced periodontal disease. 16 individuals, 10 female
      and 6 male, aged 35-58 years, with advanced periodontal disease were recruited. A
      baseline examination included assessment of clinical, radiographical,
      microbiological and histopathological characteristics of periodontal disease. The
      16 patients were randomly distributed into 2 different samples of 8 subjects
      each. One sample of subjects received during the first 2 weeks of active
      periodontal therapy, antibiotics administered via the systemic route
      (metronidazole and amoxicillin). During the corresponding period, the 2nd sample
      of subjects received a placebo drug (placebo sample). In each of the 16 patients,
      2 quadrants (1 in the maxilla and 1 in the mandible) were exposed to non-surgical
      subgingival scaling and root planing. The contralateral quadrants were left
      without subgingival instrumentation. Thus, 4 different treatment groups were
      formed; group 1: antibiotic therapy but no scaling, group 2: antibiotic therapy
      plus scaling, group 3: placebo therapy but no scaling, group 4: placebo therapy
      plus scaling. Re-examinations regarding the clinical parameters were performed,
      samples of the subgingival microbiota harvested and 1 soft tissue biopsy from 1
      scaled and 1 non-scaled quadrant obtained 2 months and 12 months after the
      completion of active therapy. The teeth included in groups 1 and 3 were following
      the 12-month examination exposed to non-surgical periodontal therapy, and
      subsequently exited from the study. Groups 2 and 4 were also re-examined 24
      months after baseline. The findings demonstrated that in patients with advanced
      periodontal disease, systemic administration of metronidazole plus amoxicillin
      resulted in (i) an improvement of the periodontal conditions, (ii)
      elimination/suppression of putative periodontal pathogens such as A.
      actinomycetemcomitans, P. gingivalis, P. intermedia and (iii) reduction of the
      size of the inflammatory lesion. The antibiotic regimen alone, however, was less
      effective than mechanical therapy with respect to reduction of BoP - positive
      sites, probing pocket depth reduction, probing attachment gain. The combined
      mechanical and systemic antibiotic therapy (group 2) was more effective than
      mechanical therapy alone in terms of improvement of clinical and microbiological
      features of periodontal disease.

PMID- 9650871
TI  - Effect of a triclosan/copolymer dentifrice on the incidence of periodontal
      attachment loss in adolescents.
AB  - The aim of this study was to assess the effectiveness of a dentifrice containing
      0.3% triclosan, 2.0% copolymer and 0.243% sodium fluoride (Colgate Total) in the
      prevention of periodontal attachment loss in adolescents. A 3-year, double-blind,
      randomised, controlled, clinical trial was conducted on 641 adolescents,
      initially aged 11-13 years. The participants were enrolled from schools in
      economically deprived areas of Manchester, England, which had a high % of Asian
      pupils originating from India, Pakistan and Bangladesh. After the baseline
      examination, which included assessments of pocket depth, attachment loss and
      subgingival calculus, the adolescents were randomly allocated to use either a
      triclosan/copolymer or control dentifrice. The control was identical to the test
      dentifrice with the exception that it did not contain triclosan/copolymer.
      Participants were re-examined after 18 and 36 months. After 3 years, a total of
      239 adolescents remained in the test and 241 in the control group. The prevalence
      of attachment loss increased from 2% at baseline to 24% after 3 years. The mean
      increment of attachment loss during the study was 0.025 mm per site in the
      control group and 0.018 mm per site in the test group. A linear regression model
      showed a statistically significant difference in attachment loss between the test
      and control group, in adolescents with high mean pocket depths at baseline. No
      adverse effects attributable to the test or control dentifrices were observed
      during the study. This study has demonstrated that unsupervised use of a
      triclosan/copolymer dentifrice can significantly reduce periodontal attachment
      loss, particularly in adolescents with high mean pocket depths.

PMID- 9650872
TI  - Association of crevicular fluid elastase-like activity with histologically
      confirmed attachment loss in ligature-induced periodontitis in beagle dogs.
AB  - Experimental periodontitis was induced using ligatures in 6 beagle dogs over 57
      days. Levels of elastase like activity in healthy sites, gingivitis sites, and in
      sites ligated for different time points were analyzed with respect to levels of
      histologically confirmed attachment loss. Attachment loss increased with
      increasing periods of ligation and reached a maximum of 0.15 mm at 57 days.
      Maximum loss of histological attachment was found to coincide with the period of
      maximum enzyme activity; during the first 7 days of ligature. Spearman
      correlation analysis of enzyme activity with attachment loss yielded a
      significant correlation (0.73, p=0.0396). The healthy and gingivitis sites were
      found to have minimal levels of enzyme activity throughout. Thus, this
      prospective study in beagle dogs found a relationship between histologically
      confirmed attachment loss and increased levels of elastase like activity
      indicating the probable usefulness of this parameter, either alone or in
      conjunction with other markers, for disclosing active periodontitis.

PMID- 9650873
TI  - The effects of an ultrasonic toothbrush on plaque accumulation and gingival
      inflammation.
AB  - The purpose of this study was to evaluate the effectiveness of an ultrasonic
      toothbrush to reduce plaque and gingival inflammation when compared to a manual
      toothbrush. 62 healthy adult patients with a plaque index of at least 2.0, a 50%
      bleeding index and at least 16 natural teeth participated in this study. 31
      patients were randomly assigned to the manual toothbrush group (group A) and 31
      were assigned to an ultrasonic toothbrush group (group B). The Turesky et al.
      plaque index (PI), Eastman bleeding index, and Loe & Silness gingival index (GI)
      were performed at baseline, 15, and 30 days at the beginning of each appointment
      (pre-brushing). Patients then brushed with their assigned toothbrush and a post
      brushing plaque index was recorded. Kruskal-Wallis one-way analysis of variance
      (ANOVA) was performed to determine between group differences on the parameters of
      all clinical indices. Results of the pre-brushing plaque index in group B were
      significantly lower at 15 and 30 days compared to group A. The post-brushing
      plaque index demonstrated no statistically significant between or within group
      differences. Both groups demonstrated significant within group reductions in GI
      and BI from baseline to 15 days and from 15 to 30 days, however, no between group
      differences were noted. The results of this study support the ability of an
      ultrasonic toothbrush to significantly remove plaque and reduce inflammation as
      well as a manual toothbrush over a 30 day period.

PMID- 9650874
TI  - Differential clinical treatment outcome after systemic metronidazole and
      amoxicillin in patients harboring Actinobacillus actinomycetemcomitans and/or
      Porphyromonas gingivalis.
AB  - 48 adult patients with untreated periodontitis harboring subgingival
      Actinobacillus actinomycetemcomitans and/or Porphyromonas gingivalis as assessed
      by PCR were randomly assigned to receive full-mouth scaling alone (control) or
      scaling with systemic metronidazole plus amoxicillin and supragingival irrigation
      with chlorhexidine digluconate (test). In patients harboring A.
      actinomycetemcomitans intraorally at baseline, the adjunctive antimicrobial
      therapy resulted in a significantly higher incidence of probing attachment level
      (PAL) gain of 2 mm or more compared to scaling alone over 12 months (p<0.05). In
      addition, suppression of A. actinomycetemcomitans in subgingival plaque below
      detectable levels was associated with an increased incidence of PAL gain. In
      contrast, patients initially harboring P. gingivalis but not A.
      actinomycetemcomitans in the oral cavity showed a significantly higher incidence
      of PAL loss following adjunctive antimicrobial therapy compared to scaling alone
      (p<0.05). When the presence of pathogens at baseline was disregarded in the
      analysis, adjunctive antimicrobial therapy did not significantly enhance clinical
      treatment outcome. The results indicated that adults with untreated periodontitis
      harboring A. actinomycetemcomitans may benefit from the adjunctive antimicrobial
      therapy for a minimum of 12 months, whereas, the regimen may adversely affect the
      clinical treatment outcome of patients harboring P. gingivalis but not A.
      actinomycetemcomitans.

PMID- 9650875
TI  - Instrumentation of furcation with modified sonic scaler inserts: study on
      manikins, part I.
AB  - The purpose of this study was to determine the suitability of different scaling
      instruments for the debridement of furcations. 12 upper and 12 lower replicated
      molars with through-and-through furcations were instrumented 3x with 5 different
      types of instruments: (i) hand instruments; (ii) hand instruments in conjunction
      with diamond burrs; (iii) a conventional ultrasonic scaler insert; (iv) a
      conventional sonic scaler insert; (v) a set of 2 modified diamond coated sonic
      scaler inserts with different angulated shafts. The plastic replicas were fixed
      in a manikin head without replicated soft tissues. Following debridement, weight
      loss and % of instrumented furcation area were assessed. In the case of lower
      molars, it made little difference whether they were treated with hand
      instruments, hand instruments combined with diamond burrs, or diamond-coated
      sonic scaler inserts. On upper molars, however, significantly more area was
      instrumented with the diamond-coated inserts than with the other instruments.
      Substance removal was greater with diamond-coated inserts than with the other
      devices. In conclusion, an effective debridement of the furcation seems possible
      only with an odontoplasty, in which a furcation is fitted to the instrument by
      means of intensive instrumentation, thus leading to substance loss. To improve
      results with these instruments, further research is necessary.

PMID- 9650876
TI  - Hyper-reactive peripheral neutrophils in adult periodontitis: generation of
      chemiluminescence and intracellular hydrogen peroxide after in vitro priming and
      FcgammaR-stimulation.
AB  - We have earlier reported a higher Fcgamma-receptor (FcgammaR)-mediated generation
      of reactive oxygen species, measured as luminol-enhanced chemiluminescence (CL)
      from peripheral neutrophils in adult periodontitis patients. The aims of this
      study were to confirm our previous results and to elucidate the mechanism of this
      phenomenon by measuring CL in parallel with the intracellular production of
      hydrogen peroxide, after stimulation with opsonized bacteria. To determine
      whether the higher CL was associated with altered responsiveness to priming, the
      cells were preincubated with tumor necrosis factor alpha (TNFalpha) and
      lipopolysaccharide (LPS). While CL was significantly higher in subjects with
      periodontitis, there was no difference in hydrogen peroxide production between
      the patients and the controls, indicating that the hyperreactivity is related to
      the generation of other oxygen species than H2O2 and/or to processes in the outer
      cell membrane. The responsiveness to priming with LPS on CL was slightly but not
      significantly higher in the periodontitis group, suggesting that priming could be
      of value for distinguishing subjects with periodontitis. When assaying
      intracellular production of H2O2, TNFalpha and LPS had both a priming and an
      activating effect. There were no significant differences between the two groups.
      In conclusion, this study shows a higher FcgammaR-mediated CL of peripheral
      neutrophils from adult patients with periodontitis, thus confirming our earlier
      results. The hyperreactivity seems to be related to the outer cell membrane or to
      oxygen species other than H2O2.

PMID- 9650877
TI  - The effect of herbal extracts in an experimental mouthrinse on established plaque
      and gingivitis.
AB  - The purpose of the present study was to establish in vitro the inhibiting effect
      of a herbal extract mixture on a selected number of micro-organisms and to test
      in vivo the effect of a mouthwash containing 6.3 mg/ml herbal extract mixture on
      plaque and gingivitis as compared to a minus active control mouthrinse. The
      herbal extract was a mixture of: Juniperus communis (juniper), Urtica dioca
      (nettle), Achillaea millefolium (yarrow); 1:1:1. In the study, in-vitro, the
      effect of pure herbal extract mixture on acid production of Streptococcus mutans
      was tested and the minimum inhibitory concentrations (MIC) of the following micro
      organisms were tested: Streptococcus mutans, Streptococcus mitis, Actynomyces
      viscosus, Actynomyces naeslundii, Actinobacillus actinomycetemcomitans,
      Prevotella intermedia, Campylobacter rectus, Fusobacterium nucleatum, Veillonella
      parvula. The MIC-values for A. viscosus and P. gingivalis were 100 mg/ml. The MIC
      values for A. naeslundii and A. actinomycetemcomitans were considerably lower (10
      mg/ml). S. mitis was the most susceptible of the tested organisms to the extract
      with a MIC value of 1 mg/ml. S. mutans, C. rectus, V. parvula, and F. nucleatum
      were not influenced by the extracts. No inhibitory effect of the 6.3 mg/ml herbal
      extract mixture was observed on the acid production of S. mutans. For the study
      in-vivo, 45 volunteers were selected on the basis of having moderate gingival
      inflammation. As efficacy parameters the plaque index, modified gingival index
      and angulated bleeding index were assessed. The subjects were randomly divided
      among 3 experimental groups (2x test and 1 'minus active' control). The
      participants were requested to rinse with 10 ml of mouthwash twice a day for a
      period of three months. After 6 weeks and 3 months, the same clinical indices as
      at baseline were recorded. The results show no difference between the two test
      groups and the control group. In conclusion, the results of the present study
      have shown that the mixture of the 3 herbal extracts, Juniperus communis, Urtica
      dioca and Achillaea millefolium when used in a mouthrinse has no effect on plaque
      growth and gingival health.

PMID- 9650878
TI  - Human periodontal ligament fibroblast response to PDGF-BB and IGF-1 application
      on tetracycline HCI conditioned root surfaces.
AB  - The purpose of this study was to investigate the effect of 2 growth factors,
      platelet-derived growth factor-BB (PDGF-BB) and insulin-like growth factor-1 (IGF
      1), alone or in combination, on the adherence of human periodontal ligament
      fibroblast (PDL) to tetracycline HCl (TTC) conditioned and nonconditioned
      periodontally involved root surfaces. There were 80 root dentine chips from 80
      patients, ranging from 35 to 70 years of age, each with one periodontally
      involved tooth requiring extraction. A root dentine chip was obtained from the
      subgingival surface opposite to the periodontal pocket of each extracted tooth.
      The dentine chips were randomly distributed into one of 8 groups. In group 1, PDL
      fibroblasts were cultured and allowed to attach on the dentine surface. In group
      2, PDL fibroblasts were cultured on a PDGF-BB pre-treated dentine surface and in
      group 3, they were cultured on a IGF-1 pre-treated dentine surface. In group 4,
      PDL fibroblasts were cultured on a dentine surface pretreated with a combination
      of PDGF-BB and IGF-1. In group 5, PDL fibroblasts were cultured and allowed to
      attach on the TTC conditioned dentine surfaces. In groups 6 and 7, surface of
      dentine chips were conditioned with TTC and then were treated with PDGF-BB or IGF
      1 respectively, followed by placement of PDL fibroblast and cultured. In group 8,
      dentine surfaces were conditioned with TTC and then pre-treated with a
      combination of PDGF-BB and IGF-1 before the fibroblasts were cultured. After 24 h
      of incubation, the media was removed and samples were fixed and processed for SEM
      at magnifications of x34, x750, x2000. Photographing and evaluation of samples
      was performed at x750 in which fibroblast adherence was measured by counting
      cells within a standard test area. The results of the non-TTC conditioned root
      surfaces demonstrated a significant increase in fibroblasts adherence in the PDGF
      BB and combination PDGF-BB/IGF-I treatment groups (groups 2, 4) when compared to
      the control (group 1) as well as the TTC control (group 5). The combination of
      PDGF-BB/IGF-1 (group 4) did not significantly improve the adhesion of cells
      compared to PDGF-BB alone (group 2), but did significantly improve adhesion when
      compared to IGF-1 alone (group 3). There were no significant differences in cell
      morphology between the growth factor groups (groups 2, 3, 4) and control (group
      1). In general, the cells demonstrated a flat, stellate-shaped morphology. The
      results of the TTC conditioned root surfaces, showed a statistically significant
      increase of cellular adherence in the PDGF-BB group (group 6) when compared to
      the TTC control (group 5), similar to the non-TTC group (group 2). However, the
      morphology of the cells in groups 5, 6, 7, and 8 demonstrated generally a rounded
      or oval shape with only an occasional cell exhibiting a flat form. In the
      experimental system of this study, the inclusion of PDGF-BB on the surface of
      dentine chips increased the number of adhering PDL cells, and the addition of TTC
      conditioning had little effect except to change the morphology of adhering cells.

PMID- 9650879
TI  - Relationship between the plaque removal efficacy of a manual toothbrush and
      brushing force.
AB  - This survey investigated the association between the efficacy of plaque removal
      and toothbrushing forces during a normal brushing regime. The 94 subjects
      participating in this study were requested not to brush 24 h prior to the
      experiment. Panelists brushed for 1 min with a manual toothbrush. Before and
      after brushing, plaque was assessed using the Turesky modification of the Quigley
      & Hein plaque index. A second 1-min exercise of brushing was carried out to
      assess the toothbrushing force. The mean plaque reduction was 39%, with
      vestibular surfaces being cleaned most effective (69%) and the lingual surfaces
      the least (21%). The mean brushing force was 330 g. No correlation was observed
      between efficacy and brushing force (r=0.14, p=0.16). The relationship between
      pre- and post-brushing plaque was stronger (r=0.68, p<0.001). Multiple regression
      analysis entering squared values of force as an independent variable into the
      equation, indicated that the relation between efficacy and force was not linear.
      A curve could be fitted to the plot (p=0.0004), demonstrating that up to a
      certain level of force, an increase of force is associated with an increase in
      efficacy (r=0.33, p<0.01). Beyond this point, application of higher forces
      resulted in reduced efficacy (r=-0.49, p=0.03). As was calculated in this
      particular test this 'transition' level of force was 407.4 g. The absence of a
      correlation between brushing force and plaque removal efficacy suggests that in a
      'user model' brushing situation, other factors than brushing force are of major
      influence on the amount of plaque removed.

PMID- 9650880
TI  - Probe penetration in relation to the connective tissue attachment level:
      influence of tine shape and probing force.
AB  - Previous research has shown that probing force and probe tine shape influence the
      clinically assessed probing depth. The purpose of the present study was to
      investigate the effect of tine shape and probing force on probe penetration, in
      relation to the microscopically assessed attachment level in untreated
      periodontal disease. In 22 patients, scheduled for partial or full mouth tooth
      extraction and no history of periodontal treatment, 135 teeth were selected. At
      mesial and distal sites of the teeth reference marks were cut. Three probe tines,
      mounted in a modified Florida Probe handpiece, were tested: a tapered, a parallel
      and a ball-ended; tip-diameter 0.5 mm. The three tines were distributed at random
      over the sites. At each site increasing probing forces of 0.10 N, 0.15 N, 0.20 N,
      0.25 N were used. After extraction, the teeth were cleaned and stained for
      connective tissue fiber attachment. The distance between the reference mark and
      the attachment level was determined using a stereomicroscope. The results showed
      that the parallel and ball-ended tine measured significantly beyond the
      microscopically assessed attachment level at all force levels; with increasing
      forces, the parallel tine measured 0.96 to 1.38 mm and the ball-ended tine 0.73
      to 1.06 mm deeper. The tapered tine did not deviate significantly from the
      microscopic values at the forces of 0.15, 0.20 and 0.25 N. It can be concluded
      that for the optimal assessment of the attachment level in inflamed periodontal
      conditions, a tapered probe with a tip diameter of 0.5 mm and exerting a probing
      force of 0.25 N may be most suitable.

PMID- 9650881
TI  - Gingival dimensions after root coverage with free connective tissue grafts.
AB  - Traumatic injury in the presence of a thin and narrow zone of gingival tissue may
      lead to gingival recession. Especially in class I and II recessions, root
      coverage may be accomplished with connective tissue grafts. In order to prevent
      recurrent recession, altering gingival dimensions width and thickness might be of
      advantage. In the present study, dimensions of gingiva were followed for 1 year
      after root coverage with connective tissue grafts. The study population consisted
      of 18 patients with a total of 28 class I or II recessions. Gingival width and
      depth of the recession were measured with a caliper, and thickness of the
      marginal tissue with an ultrasonic device. Periodontal probing depth was
      determined with a pressure-controlled electronic probe. Mean (+/-sd) recession
      depth at baseline was 3.1+/-1.4 mm. After 12 months, coverage amounted to 74+/
      30%. Width of gingiva rose from 2.1+/-1.0 mm to 3.2+/-1.4 mm, whereas thickness
      was increased from 0.8+/-0.3 mm to 1.5+/-0.7 mm, on average. No significant
      alteration of periodontal probing depth was observed but a mean gain of clinical
      attachment of 1.7+/-1.1 mm was ascertained. In a multiple regression analysis,
      recession depth and presence of the recession in the maxilla, but not tooth type
      significantly influenced relative root coverage (R2=0.34, p<0.01). Attachment
      gain after surgery depended on baseline attachment loss and was negatively
      influenced by smoking. The present results point to the possibility of doubling
      gingival thickness after root coverage with connective tissue grafts.

PMID- 9650882
TI  - Increase in gingival inflammation under academic stress.
AB  - Several correlational questionnaire studies have observed a positive relationship
      between psychological stress and periodontal diseases. This paper analyses the
      effects of academic stress on periodontal health in a prospective quasi
      experimental design. 26 medical students participating in a major exam and the
      same number of medical students not participating in any exam throughout the
      study period volunteered for the study. Bleeding on probing was assessed 4 weeks
      prior to the exam period (baseline) and at the last day of the exam. Severe
      deterioration in gingival health from baseline to the last exam day were observed
      more frequently in exam students than in controls (p=0.014). 6 exam students but
      only 1 control person developed a severe gingivitis at at least one formerly
      healthy tooth throughout the study period. These results further support the
      hypothesis that psychological stress is a significant risk factor for periodontal
      inflammation. Future studies should examine factors mediating this relationship.

PMID- 9650883
TI  - On the discussion concerning microbiological culture and DNA probes in the
      detection of periodontopathogenic bacteria.

PMID- 9650884
TI  - Direct observation of t-butyl alcohol frozen and sublimated samples using low
      vacuum scanning electron microscopy.
AB  - Frozen biological specimens in t-butyl alcohol were examined under a low-vacuum
      environment in a "wet SEM" or "variable pressure SEM (scanning electron
      microscope)" equipped with a cooling stage and highly sensitive backscattered
      detector of the YAG type. After fixation with glutaraldehyde and osmium
      tetroxide, rat tissue blocks (tracheae and kidneys), and cultured human carcinoma
      cells were dehydrated with a graded series of t-butyl alcohol. The specimens were
      directly frozen on the cooling stage at -10 degrees C, evacuated to 20 Pa in the
      specimen chamber, and observed by detecting backscattered electrons at
      accelerating voltages of 5-6 kV. The images became clearer 20 min after the
      vacuum reached 20 Pa and revealed had good quality by 30 min, probably because t
      butyl alcohol was sublimated during the time. The cilia of tracheal ciliated
      cells, end-feet of the podocytes of the renal glomerulus, and processes of
      cultured cells were clearly observed without any serious preparation artifacts.
      Since the low-vacuum SEM of t-butyl alcohol frozen samples is both simple and
      provides high imaging quality, it is expected to be useful in a variety of
      biological fields such as the rapid pathological diagnosis.

PMID- 9650885
TI  - Immunocytochemical localization of chromogranin A and secretogranin II in female
      rat gonadotropes.
AB  - Ultrastructures of pituitary gonadotropes are known to show a prominent sex
      related difference: typical male rat gonadotropes contain both large- and small
      sized granules, whereas typical female rat gonadotropes appear to exhibit
      uniformly small-sized granules. Our preceding studies have demonstrated that two
      representative granins, chromogranin A (CgA) and secretogranin II (SgII), are
      separately localized to each type of granule in male rat gonadotropes. To clarify
      whether or not there is a certain relationship between granin proteins and
      characteristic features of secretory granules in female rat gonadotropes, we
      examined the expression levels and immunocytochemical localizations of CgA and
      SgII in the cells. Northern blot and immunoblot analyses demonstrated that both
      CgA and SgII were synthesized and stored in the female pituitary, although the
      amount of CgA was much lower in the female than that in the male pituitary.
      Immunocytochemical observations clarified that gonadotropes in the female
      pituitary possessed intermediate secretory granules containing both CgA and SgII,
      in addition to solely CgA-positive and SgII-positive ones. However, secretory
      granules containing CgA in the female gonadotropes were much smaller in size and
      appeared less frequently than those in the male cells, whereas no sexual
      difference was discerned in SgII-positive granules. Moreover, the size and
      appearance of CgA-positive secretory granules varied depending on stages of the
      estrous cycle. These findings suggest that the size and appearance of secretory
      granules containing CgA are closely associated with the expression and storage
      levels of CgA in the pituitary.

PMID- 9650886
TI  - Evidence for polymorphism of Merkel cells in the adult human oral mucosa.
AB  - We recently reported that Merkel cells in the normal palatine mucosa of adult
      rodents are highly polymorphic. In order to ascertain whether or not this
      polymorphism is also evident in the human oral mucosa, palatine mucosae from
      cadavers without oral diseases and perilesional palatine mucosae of patients with
      pleomorphic adenoma were examined by immunohistochemistry using an antibody
      against cytokeratin 20. Findings showed that Merkel cells in the human normal
      palatine mucosa were polymorphic, and a number of irregular-shaped Merkel cells
      (dendritic Merkel cells) with apparent cytoplasmic projections were present among
      typical oval to round Merkel cells. The mucosa usually contained a small number
      of oval to round Merkel cells residing in ectopic places such as prickle and
      granular cell layers. On the other hand, the slightly inflamed perilesional
      palatine mucosa contained an increased incidence of dendritic Merkel cells.
      Ectopic Merkel cells were rare in the perilesional palatine mucosa.
      Characteristics of dendritic Merkel cells were examined using specimens from
      perilesional palatine mucosae by means of immunohistochemistry and electron
      microscopy. It was shown that every dendritic Merkel cell and most roundish
      Merkel cells in the perilesional mucosa lacked innervation. Electron microscopy
      suggested that dendritic Merkel cells release secretory granules from the tip of
      the cytoplasmic process and the basal cytoplasm towards the lamina propria
      mucosae, in a manner resembling the case of similar cells in rodents.

PMID- 9650887
TI  - Molecular weight-dependent effects of hyaluronate on the arthritic synovium.
AB  - Intra-articular injection of hyaluronate (HA) is widely used in the treatment of
      arthropathies. However, the mechanism of the effects of HA preparations on the
      arthritic synovium and the relationship between their effects and molecular
      weights (MW) remains unknown. The objectives of this study were to compare the
      effects of two hyaluronate preparations, HA84 (MW: 84 X 10(4)) and HA230 (MW: 230
      X 10(4)), on the synovium of an arthritis model and to examine the mechanism of
      the effects of HA. The HA preparations were intra-articularly injected in a model
      of canine arthritis induced by anterior cruciate ligament transection for a total
      trial of 5 weeks. To define the accessibility of HA preparations to the synovial
      lining layers, fluorescein-labeled HA84 or HA230 was injected at the last
      administration. Pathological changes analyzed included increases in volumes and
      prostaglandin E2 concentrations in synovial fluids, thickening of the synovial
      lining layers, vacuolar alterations in the lining cells, and stainability of HA
      in the synovium. Expression levels of Heat shock protein 72 (Hsp72) were
      immunohistochemically detected in the tissues to investigate the ability of the
      cells to survive the degeneration. The pathological changes described above were
      more significantly suppressed in the HA84-treated than in the HA230-treated
      groups. In most cases of the HA84-treated group (five cases out of six),
      fluorescein particles were intensely distributed in the synovial lining layers,
      but only two cases in the HA230-treated group showed a weak distribution of
      fluorescein particles in the layers, indicating a certain difference in the
      accessibility of HA preparations to the lining cells between the two HA
      molecules. Moreover, the immunoreactivity for Hsp72 in the lining cells as more
      intense in the HA84-treated than in the HA230-treated groups. The difference in
      the accessibility of HA molecules corresponded well with that in the inducibility
      of Hsp72 in the lining cells. These results suggest that the up-regulation of
      Hsp72 may offer a new concept concerning mechanism of the effects of HA
      preparations on the arthritic synovium.

PMID- 9650888
TI  - Development of diaphragmatic lymphatics: the process of their direct connection
      to the peritoneal cavity.
AB  - The development of the lymphatic system in the rat diaphragm was studied from
      embryonic day 16 to 25 weeks after birth by histochemistry for 5'-nucleotidase,
      scanning electron microscopy of KOH-treated or intact tissues, and transmission
      electron microscopy of thin sections. On embryonic day 16, distinct lymphatics
      were noted in the subpleural space of the diaphragm periphery. The endothelial
      cells at this stage contained an abundance of rough endoplasmic reticulum, a
      developed Golgi apparatus and mitochondria, and fewer pinocytotic vesicles than
      those in adults. The subpleural lymphatics subsequently increased and formed a
      polygonal network. They possessed many valves, and by postnatal week 6, some
      thick collecting lymphatics became endowed with smooth muscle cells. On embryonic
      day 19, some lymphatics appeared in the subperitoneal space. They extended
      centripetally and had many lateral projections that subsequently became elongated
      and connected with those from adjacent lymphatics, thus forming a lattice-like
      network. During the early postnatal days, the subperitoneal lymphatics projected
      many bulges that subsequently became elongated, and came into contact with the
      pores among the mesothelial cells, thus forming lymphatic stomata connecting the
      lymphatic lacunae to the peritoneal cavity. The lymphatic stomata increased until
      postnatal week 10. The results show that lymphatics appear as early as embryonic
      day 16 in the subpleural space of the diaphragm periphery, and develop with age
      by sprouting to form networks in both the subpleural and the subperitoneal
      spaces, and that the direct connection of the lymphatic lacunae to the peritoneal
      cavity is formed after birth.

PMID- 9650889
TI  - Immunohistochemical identification of type B intercalated cells in the rat kidney
      by a monoclonal antibody.
AB  - We recently produced monoclonal antibodies using macrophagic cells derived from
      cultured rat glomeruli as the antigen. One of the antibodies, named OS-3, was
      found to detect a cell population scattered in collecting ducts of the rat kidney
      as well as macrophages in various tissues. The present study deals with the
      cellular and subcellular localization of immunoreactivities with OS-3 in the
      kidney and other organs of rats. Double immunostaining using OS-3 and an anti
      serum against either calbindin or epidermal cytokeratin showed that OS-3
      immunoreactive cells exist exclusively in both the connecting segment and
      cortical collecting duct, and differ from calbindin- or cytokeratin-positive
      epithelial cells. Ultrastructurally, OS-3-immunoreactive cells appeared spherical
      in shape with few cytoplasmic microprojections on the narrow apical surface.
      Their relatively dark cytoplasm contained numerous mitochondria and a developed
      tubulo-vesicular system. The intense immunoreactivity was selectively localized
      in the basolateral membrane exhibiting shallow but complicated infoldings.
      Distribution and ultrastructural properties of the OS-3-immunoreactive cells
      showed that they were type B intercalated cells, which are engaged in the
      regulation of the acid-base balance mainly by secreting HCO3-. Another positive
      staining with OS-3 was found in the macula densa and some epithelial cells of
      Bowman's capsule, the former monitoring Cl- concentrations in the urine.
      Immunoblotting of extracts from the rat kidney demonstrated a protein band
      immunoreactive to OS-3 at a molecular weight of 43 kDa. Aside from the kidney, a
      specific and intense immunoreactivity with OS-3 was also found in the epithelial
      cells of the pancreatic excretory duct and in the secretory cells of the
      salivary, pyloric and duodenal glands, all of which are HCO3- -secreting cells.
      These immunohistochemical findings imply that OS-3 is useful for the detection of
      type B intercalated cells and recognizes a functional molecule involved in the
      production/secretion of HCO3- or transport of Cl-.

PMID- 9650890
TI  - Novel S100 proteins in human esophageal epithelial cells: CAAF1 expression is
      associated with cell growth arrest.
AB  - CAAF1 and CAAF2, newly identified calcium-binding proteins from bovine amniotic
      fluid, have been revealed to be members of the S100 protein family preferentially
      produced by fetal squamous epithelial cells, including epidermal keratinocytes.
      Having previously cloned the cDNA of human CAAF1 protein from the esophageal
      epithelium, we report here on the characteristic expression pattern of CAAF1 and
      related S100 proteins in human esophageal epithelial cells. Normal cells of the
      human esophageal epithelium expressed CAAF1, and also expressed the homologous
      novel S100 proteins including CAAF2, MRP8, and MRP14, but not S100alpha. An
      immunohistochemical study with specific monoclonal antibodies against CAAF1
      proteins demonstrated that CAAF1 proteins were produced by the esophageal
      epithelial cells in the process of cell differentiation. The immature
      proliferating cells in the epithelium did not produce CAAF1 proteins, but the
      differentiated cells expressed CAAF1, which overlay the immature cells and were
      stratifying in the epithelium. These CAA 1-producing cells did not show any
      proliferating activities. Esophageal carcinoma cells did not express CAAF1,
      except for the keratinized cells with no proliferating activity. In addition, the
      forced expression of CAAF1 proteins in the carcinoma cells resulted in a marked
      decrease in DNA synthesis. These findings indicate that human esophageal
      epithelial cells express the multiple genes of S100 proteins including CAAF
      proteins, and that CAAF1 is closely associated with the terminal differentiation
      of these cells. CAAF1 expression also might play some role in cell growth.

PMID- 9650891
TI  - Embryonic development of the inner ear and otolith of the rainbow trout
      Oncorhynchus mykiss.
AB  - The embryonic development of the inner ear, especially the sensory epithelia and
      otoliths in the rainbow trout Oncorhynchus mykiss, was studied by light and
      electron microscopy. Light microscopically, the auditory vesicle, saccular
      otolith and statoacoustic ganglion were first observed by 12 days after
      fertilization, while the utricular otolith appeared at 15 days after
      fertilization. Both the saccular and utricular maculae were more developed at 22
      days after fertilization, and well developed by 27 days. The crista ampullaris of
      the horizontal canal was also developed at 27 days after fertilization, while the
      other cristae were not yet distinguished. Electron microscopically, vesicular
      structures and short microvilli were found on the sensory epithelia of the
      maculae by 15 days after fertilization. At 22 days after fertilization, the
      saccular otolith possessed 7 incremental layers, and developing cilia,
      microvilli, and aggregates of secretory materials also appeared on the apical
      surface of the sensory epithelia. At 27 days after fertilization, the apical
      surface of each hair cell was covered with a hair bundle consisting of a single
      kinocilium and a bundle of stereocilia. These findings are discussed with special
      regard to the environmental factors on early development in fishes.

PMID- 9650892
TI  - MRI findings of multiple malignant gliomas: differentiation from multiple
      metastatic brain tumors.
AB  - Multiple malignant gliomas are relatively uncommon, but are sometimes difficult
      to differentiate from multiple metastatic brain tumors. We analyzed the MR
      findings of four cases of multiple gliomas, comparing them with 12 cases of
      multiple metastatic brain tumors. All tumors were pathologically proven by
      surgical operation or autopsy. Gliomas were located in the deep white matter of
      the cerebrum, with none found in the posterior fossa. Tumors were relatively
      large, and irregular, thick, ring-like enhancement was noted after the
      administration of Gd-DTPA. Intratumoral hemorrhage was noted in only one case.
      High signal intensity on T2WI around the tumor suggested that edema was greater
      and more extensive than in metastatic tumors and was seen even in the corpus
      callosum. One autopsied case that showed this high intensity presented not only
      edema but also tumor infiltration. Metastatic tumors were located mainly in the
      corticomedullary junction of the brain. They were relatively small, and eight of
      12 tumors showed, nodular or smooth ring-like enhancement. Intratumoral
      hemorrhage was noted in four cases. Edema was noted mainly around the tumor. We
      conclude that differential diagnosis between gliomas and metastases is possible
      to some extent by MRI.

PMID- 9650893
TI  - Screening helical CT for mass screening of lung cancer: application of low-dose
      and single-breath-hold scanning.
AB  - PURPOSE: To investigate the usefulness of helical CT with low-dose and single
      breath-hold scanning for lung cancer screening. MATERIALS AND METHODS: Twenty
      four helical CT scans of the lung were performed using various parameters in 10
      healthy volunteers. The effects of tube current and pitch were evaluated by
      assessment of image quality and detection of simulated nodules. Screening helical
      CT was performed at 120 kVp, 50 mA, 1 sec/rotation, 10 mm collimation, and a
      pitch of 2.0 in 110 patients. The ability of this method to detect nodules and
      masses, focal parenchymal opacities, and diffuse fibrotic changes was evaluated
      using conventional CT as the gold standard. RESULTS: A reduction in tube current
      to 50 mA did not significantly change the assessment of image quality or
      detection of simulated nodules. Although these factors were degraded by
      increasing the pitch, there was no significant difference between 1.5 and 2.0.
      Screening helical CT permitted the entire lung to be scanned with ease during a
      single-breath-hold in all patients. This method detected 177 of 196 nodules and
      masses (87 of 91 lesions greater than 5 mm in diameter), 54 of 57 focal
      parenchymal opacities, and 15 of 15 cases with fibrotic changes. CONCLUSION:
      Screening helical CT with low-dose and single-breath-hold scanning shows promise
      for lung cancer screening.

PMID- 9650894
TI  - Evaluation of reconstructed hepatic veins with breath-hold 2D time-of-flight MR
      venography.
AB  - PURPOSE: The purpose of this study was to assess the ability of magnetic
      resonance (MR) venography to evaluate the patency of reconstructed hepatic veins
      after surgery. PATIENTS AND METHODS: Five normal volunteers with normal hepatic
      veins and eight patients who underwent reconstruction of the hepatic veins after
      resection of hepatic tumors were included. All subjects underwent breath-hold two
      dimensional (2D) time-of-flight MR venography using a fast low angle shot (FLASH)
      technique with a 1.5 Tesla magnet. The initial imaging plane was coronal, and
      sagittal and/or transverse planes were added when necessary. Data were
      postprocessed with a maximum intensity projection (MIP) algorithm. In six
      patients, the MR findings were verified by iodinated hepatic venography. RESULTS:
      The confidence level increased when patency was evaluated using a combination of
      MIP and source images or other imaging planes compared with the use of MIP images
      alone (3.0 to 3.6, p < 0.05). A signal drop near the orifice at the inferior vena
      cava was observed in three normal patients. The severity of stenosis was
      overestimated by MR venography in five patients. Obstruction was correctly
      suggested in one patient. CONCLUSION: Although 2D time-of-flight MR venography
      overestimated stenosis of the hepatic vein at the site of connection, it might
      provide information on the patency of reconstructed hepatic veins especially when
      more than one orthogonal plane is used and both MIP and source images are
      evaluated.

PMID- 9650895
TI  - CT angiography with helical CT in the assessment of acute stage of subarachnoid
      hemorrhage.
AB  - PURPOSE: We evaluated the usefulness of helical CT in the preoperative assessment
      of ruptured cerebral aneurysms during the acute stage of subarachnoid hemorrhage
      (SAH). METHODS: Nine patients with 13 aneurysms were included in this study.
      Helical CT scanning was performed before preoperative angiography. The section
      thickness and the table-movement speed were 1-2 mm/sec. Helical CT scanning was
      started 20 sec after the start of injection of 100 ml of contrast agent at a rate
      of 3 ml/sec. RESULTS: The average CT value of SAH was 51.9 Hounsfield units (HU)
      and that of the aneurysm was 191.7 HU. Nine of 13 aneurysms greater than 3.0 mm
      in diameter were identified by three-dimensional CT angiography (3DCTA). In seven
      cases, the information provided by 3DCTA images, maximum intensity projection
      images, and multiplanar images, was very useful in surgical planning, providing
      information concerning the configuration of the neck and relationships between
      the aneurysm and brain parenchyma. Four aneurysms in two cases were not depicted
      by 3DCTA because they were located outside the imaging volume. This problem was
      overcome by changing the imaging volume according to the extent of origin of SAH.
      CONCLUSION: We conclude that helical CT in patients with SAH is useful for
      surgical planning, providing valuable information that cannot be obtained by
      conventional angiography.

PMID- 9650896
TI  - Imaging techniques for measuring adipose-tissue distribution in the abdomen: a
      comparison between computed tomography and 1.5-tesla magnetic resonance spin-echo
      imaging.
AB  - Eight subjects were examined both by abdominal X-ray computed transverse axial
      tomography (CT) and magnetic resonance imaging (MRI) (SE) (TR/TE, 200 ms/15 ms);
      another eight volunteers were subjected to three MRI scans to test the
      reliability of repeated measures. Correlations between fat area measures obtained
      by CT and by MRI for subcutaneous fat, total fat, and visceral vs. subcutaneous
      fat ratio were highly significant (r = 0.93, 0.91, and 0.94, respectively; p <
      0.01), and the standard errors of estimation were 9.99, 23.87, and 0.0047. The
      average errors of the method for different fat areas were 2.20 cm2 (intra
      examination variance) and 3.75 cm2 (inter-examination variance) for visceral and
      0.82 cm2 (intra-examination variance) and 1.29 cm2 (inter-examination variance)
      for subcutaneous fat areas, respectively. These results suggest that SE MRI is a
      practical approach to evaluate body fat distribution without the exposure to
      radiation. The reproducibility of SE MRI for the determination of fat areas is
      high; variation is small and acceptable. However, it is difficult to determine
      which estimate of fat area should be accepted when there is a discrepancy between
      MRI and CT measures.

PMID- 9650897
TI  - Treatment in patients with glioblastoma multiforme and poor performance status:
      is it worthwhile?
AB  - It has not been ascertained that treatment of glioblastoma multiforme of the
      brain (GMB) favorably alters the prognosis in patients with poor pretreatment
      performance status (PPS). We report on 52 patients with GMB and PPS. The mean
      survival of 43 treated persons was 19 +/- 12 months (95% confidence interval) and
      of nine untreated individuals, 2 +/- 1 months (p > 0.50); the corresponding
      survival rates at 1 year were 39 +/- 16% and 0% (p > 0.05) and at 2 years, 15 +/-
      12% and 0% (p > 0.40). We recommend active treatment of patients with GMB even
      when they present with poor functional status.

PMID- 9650898
TI  - Prognostic value of anti-Epstein-Barr virus antibodies in nasopharyngeal
      carcinoma (NPC).
AB  - INTRODUCTION: Epstein-Barr virus (EBV) is a ubiquitous human herpes virus with
      worldwide infection. It is associated with Burkitt's lymphoma in Africa and
      nasopharyngeal cancer (NPC) in Asian countries. EBV-coded DNA was found to be
      present in epithelial elements of NPC, and is usually associated with non
      keratinizing (WHO type II) or undifferentiated carcinoma (WHO type III).
      Transcriptional analyses of EBV genome expression in NPC demonstrate an activated
      viral state in some of these tumors, leading to elevated levels of serum anti
      viral capsid antigen (VCA) antibody in NPC patients. METHODS: Eighty patients
      with histological diagnoses of NPC according to the 1978 WHO classification were
      referred to the Department of Radiation Oncology at Chang-Hua Christian Hospital
      for curative radiotherapy from 1985 to 1995. The patients were staged according
      to the AJCC staging system. A mean dose of 7,020 cGy in 39 fractions was
      delivered to the primary tumor using a telecobalt-60 unit or 6-10 MV X-ray linear
      accelerator. Pre- and postradiotherapy serum levels of anti-EBV/VCA IgG and IgA
      were determined for all patients using the indirect immunoperoxidase assay (IPA).
      Multivariate analysis was done to determine which factors affected the patients'
      treatment outcome and survival. RESULTS: Five patients were excluded from this
      study due to incomplete radiotherapy, leaving 75 patients eligible for analysis.
      Overall local control was 77.3%, with a mean disease-free interval of 19.7
      months. Factors affecting local control included radiation dose and pretreatment
      anti-EBV/VCA IgG titer. The overall 5-year actuarial survival for the 75 patients
      was 75%, with a median survival of 129.5 months. The 5-year actuarial survival
      rates for stage I + II, III, and IV patients were 90%, 40%, and 45%,
      respectively. Prognostic factors for survival included tumor histological type
      and pretreatment anti-EBV/VCA IgA titer, while prognostic factors for local
      control included total radiation dose received and pretreatment anti-EBV/VCA IgG
      titer. CONCLUSION: We found that there was a significant difference in the
      geometric mean titer of anti-EBV/VCA IgA antibodies before and after
      radiotherapy. Prognostic factors affecting NPC patients' actuarial survival
      included tumor histology and pretreatment IgA titer, while prognostic factors for
      local control of NPC included total radiation dose received and pretreatment IgG
      titer.

PMID- 9650899
TI  - Pitfalls of CT diagnosis of aortic dissection: nonvisualized intimal flap in the
      ascending aorta or aortic arch.
AB  - We describe our experience with initial CT scans that failed to demonstrate an
      intimal flap in the ascending aorta or aortic arch that was subsequently
      identified on echocardiography, angiography, or MR imaging in four patients. This
      problem was presumably caused by the flailing motion of a thin intimal flap and
      localized small dissection in the ascending aorta, or transverse intimal flap
      within the aortic arch. Radiologists should be aware of this pitfall in CT
      diagnostic imaging.

PMID- 9650900
TI  - Appendiceal abscess mimicking infected urachal cyst in a child with intestinal
      malrotation.
AB  - An appendiceal abscess with intestinal malrotation can occur anywhere in the
      abdomen, not only in the right lower quadrant. We report a case presenting a
      midline mass of the lower abdomen whose computed tomography (CT) and
      ultrasonography (US) findings mimicked a urachal abscess. A retrospective review
      of CT findings led to the correct diagnosis by showing malposition of the
      ascending colon.

PMID- 9650901
TI  - A case of chest wall Castleman's disease.
AB  - We describe the findings of a rare case of right anterior chest wall Castleman' s
      disease of the hyaline vascular type. It manifested as a solitary mass, 7.5 x 4.5
      x 3.0 cm in size, with incomplete border and extrapleural signs on chest
      roentgenograms. The mass was hypoechoic with numerous tiny bright spots on US; it
      enhanced homogeneously on CT, had a homogeneously high intensity on both T1- and
      T2-weighted MR images, and showed rich vascularity with homogeneous capillary
      blush on internal thoracic arteriogram.

PMID- 9650902
TI  - Case report: MR findings of Guillain-Barre syndrome.
AB  - Guillain-Barre syndrome (GBS) is characterized as an acute, symmetrically
      progressive, inflammatory demyelinating polyneuropathy. We report a case of GBS
      in which gadolinium-enhanced magnetic resonance (MR) imaging showed marked
      enhancement of nerve roots of the conus medullaris and cauda equina. On enhanced
      MR imaging, the spinal cord and nerve roots in the thecal sac generally do not
      take up much gadolinium because of the blood-nerve barrier or blood-brain
      barrier. Therefore, in our case, marked enhancement of nerve roots indicates a
      breakdown of the blood-nerve barrier. It is thought to correlate with the
      inflammatory infiltration of GBS.

PMID- 9650903
TI  - Primary central nervous system lymphoma presenting as diffuse cerebral
      infiltration.
AB  - We report a case of primary central nervous system lymphoma presenting as diffuse
      cerebral infiltration. On T2-weighted spin echo MR imaging using a 1.0 Tesla
      unit, high signal intensity lesions were presented mainly in the bilateral
      pyramidal tracts and also diffusely extended to white matter with brain swelling.
      No enhancing lesion was demonstrated after the intravenous injection of
      Gadolinium-DTPA, during the course of her disease. Radiological diagnosis of
      gliomatosis cerebri was made because of the characteristic MR appearance.
      Stereotactic biopsy was performed, and diffusely scattered lymphocytes, probably
      neoplastic, in the cerebral white matter were demonstrated histopathologically.
      Oral corticosteroids, radiation therapy, and chemotherapy were applied soon after
      her admission. The patient's condition improved dramatically. MR imaging using a
      1.5 Tesla unit after the treatments showed marked regression and reduction of
      high intensity lesions on T2-weighted images and improvement of brain swelling.
      It should be emphasized that brain biopsy is important method for correct
      diagnosis in case of diffuse non-enhancing brain lesions like our case.

PMID- 9650904
TI  - Endovascular management of an aneurysm arising from posterior inferior cerebellar
      artery originated at the level of C2.
AB  - A 22-year-old man was admitted with a spontaneous subarachnoid hemorrhage. Right
      vertebral angiography demonstrated an aneurysm arising from a distal segment of
      an anomalous posterior inferior cerebellar artery (PICA) at the level of C 1. The
      PICA originated from the third segment of the vertebral artery at the level of
      C2. The lesion was treated with endovascular techniques, and the patient suffered
      no residual neurological deficits.

PMID- 9650905
TI  - Percutaneous fenestration of type B aortic dissection for decompression of false
      lumen pressure: case report.
AB  - We describe our experience with percutaneous treatment by transfemoral balloon
      fenestration of the abdominal aorta in a patient with type B aortic dissection.
      Percutaneous fenestration was effective in reducing the pressure in the false
      lumen and equalizing the pressure between the two lumens. The patient was doing
      well at three-year follow-up.

PMID- 9650906
TI  - Effect of the distribution of radioactive sources on deadtime loss in a single
      crystal gamma camera.
AB  - Quantitative studies with a single-crystal gamma camera often require correction
      for deadtime count loss. We evaluated the deadtime characteristics of a gamma
      camera using point sources. Point sources with various radioactivities were
      measured, and the relation between radioactivity and count rate was assessed. Two
      sources with different activities were imaged apart or adjacent to each other,
      and the effect of the geometrical distribution on counting efficiency was
      investigated. Count loss was increased at a high radioactivity level, and was
      well corrected using a nonparalyzable model and a deadtime of 4.99 microsec. It
      was not affected by the distance between the two sources, and occurred equally
      for the two sources imaged together. The count loss in imaging two sources was
      successfully corrected by multiplying the obtained image by a correction factor
      based on the count rate in the whole field-of-view. These results support the
      reliability of the analytic technique for deadtime correction.

PMID- 9650907
TI  - Reirradiation therapy for brain metastases from small cell lung cancer.
AB  - Three patients with recurrence of brain metastases from small cell lung cancer
      were treated with whole brain reirradiation therapy. A total dose of 20 Gy was
      administered to two patients with hyperfractionation (20 fractions) and to one
      with conventional fractionation (10 fractions). Two cases achieved PR and the
      other NC. Survival after reirradiation was four months for all patients. Two
      patients died of progressive brain metastases and one patient of liver
      metastases. No radiation injury was observed during follow-up. Whole brain
      reirradiation at a dose of 20 Gy in 10 or 20 fractions was therefore considered
      useful and safe for brain recurrence of small cell lung cancer.

PMID- 9650908
TI  - Chemoembolization of maxillary tumors via the superficial temporal artery using a
      coaxial catheter system.
AB  - A preliminary experience of embolization of maxillary tumors via the superficial
      temporal artery using a coaxial catheter system is presented. Five patients with
      maxillary carcinoma were slated to undergo embolization before radical surgery.
      Embolization with carboplatine microcapsules was performed via the superficial
      temporal artery using a coaxial catheter system. Carboplatine microcapsules
      consisted of 60% (W/W) carboplatine core and 40% (W/W) ethylcellulose shell.
      Embolization was performed twice in three patients, three times in one patient,
      and once in one patient. The interval between embolizations was from one to three
      weeks. The total dose of carboplatine microcapsules given ranged from 100 to 230
      mg. Responses to the treatment were determined by measurements of tumor reduction
      and increase in low attenuation areas of the tumor on postcontrast CT. Tumor
      reduction over 48% was achieved in four of five tumors. All the tumors showed an
      increased area of low attenuation in the tumor on the postcontrast CT after
      embolization. No significant complications occurred. This method makes it easy to
      superselectively repeat embolization.

PMID- 9650909
TI  - Relationship among age, prostate-specific antigen, and prostate volume in men
      with lower urinary tract symptoms (LUTS) and in different groups of men with and
      without benign and malignant prostate diseases.
AB  - BACKGROUND: In order to enhance prostate-specific antigen (PSA) as a predictor of
      prostate cancer, it is necessary to understand the characteristics of this tumor
      marker in a population of men without evidence of prostate cancer but who are at
      risk for developing the condition. METHODS: In an age-stratified population of
      328 men with lower urinary tract symptoms (LUTS), we analyzed the distribution of
      PSA levels as a function of age and prostate volume, and we analyzed the
      percentage of age-related variance in PSA that can be explained by the age
      related variance in prostate volume. RESULTS: Classifying the 328 cases with LUTS
      according to four age groups, a correlation was found between PSA and prostate
      volume, becoming stronger from the younger (correlation coefficient, -0.1265) to
      the older group (correlation coefficient, 0.6044). Serum PSA variance per
      milliliter of prostate volume also increased from the younger (not significant, P
      > 0.1) to the older age decades (7.3% in men age 70 years or over). Moreover, the
      results of the regression analysis suggest that 10% of the variance in PSA with
      age can be accounted for by prostate volume in men under age 50 years, reaching
      37% in men age 70 years or more. CONCLUSIONS: These data confirm that the serum
      PSA concentration increases with advancing age in the absence of clinically
      evident prostatic malignancy. In younger patients with LUTS, serum PSA variance
      with age seems to be less dependent upon the age-related variance in prostate
      volume.

PMID- 9650910
TI  - Prostate-thyroid axis: stimulatory effects of ventral prostate secretions on
      thyroid function.
AB  - BACKGROUND: Endocrine cells of the prostate secrete thyrotropin (TSH)-releasing
      hormone (TRH), TRH- and TSH-like peptides, and growth factors. Propylthiouracil-
      and methimazole-induced hypothyroidism increased prostatic levels of TRH in rats
      as in hypothalamus, whereas thyroxine (T4) replacement decreased TRH. From these
      reports, we inferred the existence of a prostate-thyroid axis. METHODS: The
      influence of the prostate on the thyroid gland was studied in albino rats.
      Ventral prostate was surgically removed on day 31 postpartum. The animals were
      sacrificed on day 60 postoperation. Serum thyroid hormones were assayed by
      radioimmunoassay (RIA). For in vitro studies, normal thyroid and ventral prostate
      glands were cocultured with or without thyroid-stimulating hormone (TSH)
      antibody, to assess the direct influence of prostatic secretions on thyroid
      hormone secretion. RESULTS: Serum total and free T4 and triiodothyronine (T3)
      were significantly reduced in ventral prostatectomized rats. Histological
      analysis of the thyroid showed that the diameters of the peripheral and middle
      follicles, colloid epithelial cells, and nuclei were increased in
      prostatectomized rats, indicating hypothyroid status. Total T3 and T4 were
      significantly elevated in the culture medium when thyroid and prostate were
      cocultured, irrespective of the presence of TSH antibody. CONCLUSIONS: The
      present study suggests that ventral prostatic secretions have a stimulatory role
      on the thyroid gland.

PMID- 9650911
TI  - Effect of bone proteins on human prostate cancer cell lines in vitro.
AB  - BACKGROUND: Despite the high incidence and serious consequences of skeletal
      metastasis in prostate cancer patients, the mechanisms involved in establishing
      secondary lesions in bone are not well-understood. In this study, the role of the
      mineralized bone matrix in the process of skeletal metastasis was evaluated.
      METHODS: Attachment, migration, and proliferation responses of human prostate
      cancer cells to a crude bone protein extract (CBE) were studied. LNCaP and DU145
      cells were utilized in 24-hr attachment assays. Boyden chamber chemotactic assays
      and cell proliferation assays utilized DU145 cells. RESULTS: CBE and fibronectin
      (FN) promoted attachment of DU145 cells, whereas only FN facilitated attachment
      of LNCaP cells. CBE-mediated adhesion of DU145 cells was reduced by 94% with
      cycloheximide, by 98% with RGD peptides, and by 94% with an antibody to
      alphavbeta3. Although DU145 cells migrated toward FN, CBE did not promote
      migration of DU145 cells. DU145 cells grown in the presence of CBE-containing
      media demonstrated a significant reduction in cell number by day 4. The
      antiproliferative effect of CBE was not due to cell toxicity. CONCLUSIONS: In
      conclusion, results from this study indicate that mineralized bone proteins
      promote the attachment of DU145 cells in vitro and suggest that bone proteins may
      play a key role in vivo during the development of metastatic prostate lesions in
      bone.

PMID- 9650912
TI  - Apoptosis and related genes in the rat ventral prostate following androgen
      ablation in response to ethane dimethanesulfonate.
AB  - BACKGROUND: Following androgen withdrawal, regression of the prostate is
      characterized by apoptotic cell death. The molecular events governing this
      process have not been fully characterized. METHODS: Using ethane-1,2
      dimethanesulfonate (EDS) to induce androgen ablation, we investigated the role of
      the Bcl-2 family members and Fas pathway in this phenomenon. Prostates were
      examined from adult male rats injected with 100 mg/kg EDS and killed 2, 5, and 8
      days later. RESULTS: Regression of the prostate was evident as a time-dependent
      decrease in weight. The number of apoptotic cells identified by in situ end
      labeling was maximal after 5 days of treatment. There was no statistically
      significant change in the expression of Bax, Bcl-xl, Bcl-2, or p53 following
      androgen withdrawal. In contrast, 5 days post-EDS treatment, testosterone
      repressed prostate message (TRPM-2) and Fas-R expression were induced. There was
      a decline in Fas-L levels 8 days after EDS administration. CONCLUSIONS: This
      study extends previous work which has shown that androgen withdrawal induces
      apoptosis in the prostate. We have shown that although p53 and the Bcl-2 family
      members examined in this study do not seem to be important in this process, the
      Fas pathway may play a role in apoptosis of the ventral prostate in response to
      androgen ablation.

PMID- 9650913
TI  - Chromosome 16q24 deletion and decreased E-cadherin expression: possible
      association with metastatic potential in prostate cancer.
AB  - BACKGROUND: Deletion of chromosome 16q is a frequent aberration in prostatic
      carcinoma, indicating the existence of candidate tumor suppressor genes involved
      in the pathogenesis of prostate cancer. METHODS: Chromosome 16 numerical
      aberration and loss of 16q were studied by fluorescence in situ hybridization in
      31 primary and 22 metastatic tumors from 53 patients. The results were compared
      with E-cadherin expression, tumor grade and stage, and DNA ploidy. RESULTS:
      Numerical chromosome 16 aberrations, 16q deletion, and loss of E-cadherin
      expression were found in 29%, 35%, and 29% of the primary tumors, respectively,
      and in 73%, 73%, and 73% of the metastases, respectively. High tumor grade and
      DNA aneuploidy were also found to have significant correlation with metastases.
      CONCLUSIONS: Deletion of chromosome 16q24 and/or loss of the E-cadherin function
      appears in a high frequency in metastases of prostate cancer. The strong
      correlations suggest that they may be important risk factors, contributing to the
      metastatic potential of the tumor.

PMID- 9650914
TI  - Evaluation of phase I/II clinical trials in prostate cancer with dendritic cells
      and PSMA peptides.
AB  - BACKGROUND: A phase I trial involving patients with advanced prostate cancer was
      conducted to assess the safe administration of dendritic cells (DC) and HLA-A0201
      specific prostate-specific membrane antigen (PSMA) peptides (PSM-P1 or -P2).
      Thirty-three of the phase I participants were subsequently enrolled in a phase II
      trial, which involved six infusions of DC pulsed with PSM-P1 and -P2 peptides.
      METHODS: Clinical monitoring was conducted up to 770 days from the start of the
      phase I study. Data collected included: complete blood count, bone and total
      alkaline phosphatase, prostate markers, physical examination, performance status,
      bone scan, ProstaScint scan, and chest X-ray, as well as assays to monitor
      cellular immune responses. RESULTS: Nine partial responders were identified in
      the phase II study based on National Prostate Cancer Project (NPCP) criteria,
      plus 50% reduction of prostate-specific antigen. Four of the partial responders
      were also responders in the phase I study, with an average response duration of
      225 days. Their combined average total response period was over 370 days. Five
      other responders were nonresponders in the phase I study. Their average partial
      response period was 196 days. CONCLUSIONS: The responses observed in the phase I
      and II clinical trials were significant and of long duration. The partial
      responder group included patients who continued to respond from phase I, as well
      as those who started to respond during the phase II trial.

PMID- 9650915
TI  - Conference summary: First International Workshop on Animal models of Prostate
      Cancer.

PMID- 9650916
TI  - Workgroup I: rodent models of prostate cancer.

PMID- 9650917
TI  - Workgroup 2: human xenograft models of prostate cancer.

PMID- 9650918
TI  - Workgroup 3: transgenic and reconstitution models of prostate cancer.

PMID- 9650919
TI  - Workgroup 4: spontaneous prostate carcinoma in dogs and nonhuman primates.

PMID- 9650920
TI  - Diagnosis of Q fever.

PMID- 9650921
TI  - Monoclonal antibody against Babesia equi: characterization and potential
      application of antigen for serodiagnosis.
AB  - Monoclonal antibody (MAb) BEG3 was produced against Babesia equi parasites to
      define a species-specific antigen for diagnostic use. The MAb reacted with
      single, paired, and Maltese cross forms of B. equi, and no reaction was observed
      with this MAb on acetone-fixed Babesia caballi, Babesia ovata, or Babesia microti
      parasites in the indirect immunofluorescent antibody test. Confocal laser and
      immunoelectron microscopic studies showed that the antigen which was recognized
      by this MAb was located on the surface of B. equi parasites. This MAb recognized
      a 19-kDa protein of B. equi antigen and did not react with B. caballi antigen or
      normal horse erythrocytes in immunoblot analysis. This MAb also significantly
      inhibited the in vitro growth of the B. equi parasite. Preliminary studies using
      partially purified antigen, which was separated by high-pressure liquid
      chromatography and recognized by the MAb, suggested that it is a suitable antigen
      for enzyme-linked immunosorbent assay detection of anti-B. equi antibodies in
      naturally infected horse sera.

PMID- 9650922
TI  - Diagnosis of Mycobacterium microti infections among humans by using novel genetic
      markers.
AB  - As a result of DNA typing of Mycobacterium microti isolates from animals in the
      United Kingdom and The Netherlands, we diagnosed four human M. microti
      infections. These are the first M. microti infections among humans to be
      reported. Three of the patients were immunocompromised and suffered from
      generalized forms of tuberculosis. The fourth patient was a 34-year-old
      immunocompetent male with a persistent cough and undefined X-ray abnormalities.
      Two of the M. microti infections were recognized by their IS6110 restriction
      fragment length polymorphism (RFLP) patterns, which showed a high degree of
      similarity with those of M. microti strains isolated from a pig and a ferret in
      The Netherlands. The two other human M. microti infections were recognized by
      using the recently developed DNA fingerprinting method, "spoligotyping," directly
      on clinical material. All M. microti isolates from the United Kingdom and The
      Netherlands were found to contain an exceptionally short genomic direct repeat
      region, resulting in identical two-spacer sequence reactions in spoligotyping. In
      contrast, the highly similar IS6110 RFLP patterns of the vole strains from the
      United Kingdom differed considerably from the RFLPs of all M. microti strains
      isolated in The Netherlands, suggesting that geographic isolation led to
      divergent strains in the United Kingdom and on the continent.

PMID- 9650923
TI  - Molecular epidemiological study of nosocomial Enterobacter aerogenes isolates in
      a Belgian hospital.
AB  - In 1995, the rate of isolation of Enterobacter aerogenes in the Saint-Pierre
      University Hospital in Brussels, Belgium, was higher than that in the preceding
      years. A total of 45 nosocomial E. aerogenes strains were collected from 33
      patients of different units during that year, and they were isolated from 19
      respiratory specimens, 13 pus specimens, 7 blood specimens, 4 urinary specimens,
      1 catheter specimen, and 1 heparin vial. The strains were analyzed to determine
      their epidemiological relatedness and were characterized by their antibiotic
      resistance pattern determination, plasmid profiling, and genomic fingerprinting
      by macrorestriction analysis with pulsed-field gel electrophoresis (PFGE). The
      majority of the strains (82%) were multiply resistant to different commonly used
      antibiotics. Two major plasmid profiles were found: most strains (64%) harbored
      two plasmids of different sizes, whereas the others (20%) contained a single
      plasmid. PFGE with SpeI and/or XbaI restriction enzymes revealed that a single
      clone (80%) was responsible for causing infections or colonizations throughout
      the year, and this result was concordant with those obtained by plasmid
      profiling, with slight variations. By comparing the results of these three
      methods, PFGE and plasmid profiling were found to be the techniques best suited
      for investigating the epidemiological relatedness of E. aerogenes strains, and
      they are therefore proposed as useful tools for the investigation of nosocomial
      outbreaks caused by this organism.

PMID- 9650924
TI  - Characterization of glycopeptide-resistant enterococci from a Swiss hospital.
AB  - Between August 1994 and September 1996, 28 glycopeptide-resistant enterococci
      (GRE) were isolated from 8 infected patients and 11 intestinal carriers
      hospitalized at the University Hospital of Geneva. Identification to the species
      was made by both phenotypic (API 20 STREP and Rapid ID 32 STREP systems, and
      Vitek Gram Positive Identification Card) and genotypic methods using a multiplex
      PCR assay developed also for the determination of the genotype of glycopeptide
      resistance (vanA, vanB, vanC1, and vanC2-C3 genes). Fifteen isolates were
      identified as Enterococcus faecium, 8 as E. gallinarum, 4 as E. faecalis, and 1
      as E. hirae. All of the phenotypic identification methods failed to differentiate
      some isolates of E. gallinarum from E. faecium, or vice versa. Both vanA (n = 18)
      and vanB (n = 4) glycopeptide resistance genotypes were found. For the first
      time, the vanB determinant was found in two isolates of E. gallinarum. Two
      patients were colonized by two different species containing the vanA gene and one
      by two different species containing the vanB gene. All vanA isolates were highly
      resistant to both vancomycin and teicoplanin except for three isolates which were
      susceptible to teicoplanin. Molecular typing by pulsed-field gel electrophoresis
      showed identical or similar patterns among E. faecium isolates with the vanA gene
      in five patients for whom the epidemiological link could not be always
      elucidated. This study emphasizes the necessity of utilizing both phenotypic and
      genotypic methods to characterize GRE.

PMID- 9650925
TI  - Characterization of IS1245 for strain typing of Mycobacterium avium.
AB  - IS1245 is an insertion element widely prevalent among isolates of Mycobacterium
      avium. We used PvuII Southern blots to analyze IS1245 polymorphisms among 159 M.
      avium isolates (141 clinical isolates from 40 human immunodeficiency virus
      infected patients plus 18 epidemiologically related environmental isolates) that
      represented 40 distinct M. avium strains, as resolved by previous studies by
      pulsed-field gel electrophoresis (PFGE). All 40 strains carried DNA homologous to
      IS1245 and thus were typeable. Twenty-five (63%) strains had > or = 10 copies of
      the element, 6 (15%) had 4 to 9 copies, and 9 (23%) had only 1 to 3 copies. Among
      the last group of nine strains (each of which was distinct by PFGE analysis),
      IS1245 typing resolved only four patterns and thus provided poor discriminatory
      power. To evaluate the in vivo stability of IS1245, we analyzed 32 strains for
      which sets of 2 to 19 epidemiologically related isolates were available. For 19
      (59%) of these sets, all isolates representing the same strain had
      indistinguishable IS1245 patterns. Within eight (25%) sets, one or more isolates
      had IS1245 patterns that differed by one or two fragments from the modal pattern
      for the isolates of that strain. Five (16%) sets included isolates whose patterns
      differed by three or more fragments; on the basis of IS1245 typing those isolates
      would have been designated distinct strains. IS1245 was stable during in vitro
      passage, suggesting that the variations observed represented natural
      translocations of the element. IS1245 provides a useful tool for molecular strain
      typing of M. avium but may have limitations for analyzing strains with low copy
      numbers or for resolving extended epidemiologic relationships.

PMID- 9650926
TI  - Use of multiple competitors for quantification of human immunodeficiency virus
      type 1 RNA in plasma.
AB  - Quantification of human immunodeficiency virus type 1 (HIV-1) RNA in plasma has
      rapidly become an important tool in basic HIV research and in the clinical care
      of infected individuals. Here, a quantitative HIV assay based on competitive
      reverse transcription-PCR with multiple competitors was developed. Four RNA
      competitors containing identical PCR primer binding sequences as the viral HIV-1
      RNA target were constructed. One of the PCR primers was fluorescently labeled,
      which facilitated discrimination between the viral RNA and competitor amplicons
      by fragment analysis with conventional automated sequencers. The coamplification
      of known amounts of the RNA competitors provided the means to establish internal
      calibration curves for the individual reactions resulting in exclusion of tube-to
      tube variations. Calibration curves were created from the peak areas, which were
      proportional to the starting amount of each competitor. The fluorescence
      detection format was expanded to provide a dynamic range of more than 5 log
      units. This quantitative assay allowed for reproducible analysis of samples
      containing as few as 40 viral copies of HIV-1 RNA per reaction. The within- and
      between-run coefficients of variation were <24% (range, 10 to 24) and <36%
      (range, 27 to 36), respectively. The high reproducibility (standard deviation,
      <0.13 log) of the overall procedure for quantification of HIV-1 RNA in plasma,
      including sample preparation, amplification, and detection variations, allowed
      reliable detection of a 0.5-log change in RNA viral load. The assay could be a
      useful tool for monitoring HIV-1 disease progression and antiviral treatment and
      can easily be adapted to the quantification of other pathogens.

PMID- 9650927
TI  - Detection of Echinococcus multilocularis in the definitive host: coprodiagnosis
      by PCR as an alternative to necropsy.
AB  - Recently, extensions of the range of Echinococcus multilocularis in Europe and
      North America and drastic increases in fox populations in Europe put an
      increasing proportion of the human population at risk of alveolar echinococcosis.
      To obtain data on the local infection pressure, studies of the prevalence of the
      parasite in the animals that transmit the parasite, foxes, dogs, and cats, are
      urgently required. Such investigations, however, have been hampered by the need
      for necropsy of the host animal to specifically diagnose infection with the
      parasite. In this study, a nested PCR and an improved method for DNA extraction
      were developed to allow the sensitive and specific diagnosis of E. multilocularis
      infections directly from diluted fecal samples from foxes. The target sequence
      for amplification is part of the E. multilocularis mitochondrial 12S rRNA gene.
      The specificity of the method was 100% when it was tested against 18 isolates
      (metacestodes and adult worms) of 11 cestode species, including E. granulosus.
      The sensitivity of the method was evaluated by adding egg suspensions and
      individual eggs to samples of diluted feces from uninfected foxes. The presence
      of one egg was sufficient to give a specific signal. To confirm the PCR results,
      an internal probe which hybridized only with E. multilocularis amplification
      products but not with the DNA of other cestodes was constructed. In order to
      investigate the applicability of this method for epidemiological studies, 250
      wild foxes from a area in southern Germany where echinococcosis is highly endemic
      were examined by both necropsy and PCR of rectal contents. The sensitivity
      correlated with the parasites' number and stage of maturity. It ranged from 100%
      (>1,000 gravid worms) to 70% (<10 nongravid worms). On the basis of positive PCR
      results for 165 foxes, the sensitivity of the traditional and widely used
      necropsy method was found to be not higher than 76%. We therefore present this
      PCR system as an alternative method for the routine diagnosis of E.
      multilocularis in carnivores.

PMID- 9650928
TI  - Use of monoclonal antibodies to identify serotypes of enterovirus isolates.
AB  - Nonpoliovirus enteroviruses cause a variety of diseases that are common in young
      children and adults. The "gold standard" for laboratory diagnosis of
      enteroviruses is cell culture isolation, followed by serotype identification by
      neutralization assay. These procedures are time-consuming and expensive. Rapid
      serotype identification of enteroviruses is important in differentiating
      nonpoliovirus enterovirus pathogens from vaccine strain polioviruses that can be
      shed for some time after vaccination. In the present investigation, we evaluated
      a rapid method for serotype identification of enteroviruses by indirect
      immunofluorescence assay (IFA) using commercially available monoclonal antibodies
      for polioviruses, coxsackieviruses type B, and six serotypes of commonly
      circulating echoviruses. Of 291 isolates of enteroviruses included in the study,
      95 were polioviruses and 196 were nonpoliovirus enteroviruses. Two hundred thirty
      four of these (38 polioviruses and 196 nonpoliovirus enteroviruses) were
      consecutively grown in the laboratory over a 5-year period. IFA identified the
      serotypes of 74% of the consecutive isolates and 71% of all enterovirus isolates
      by yielding a positive staining result. The levels of agreement in the
      identification of the enterovirus group between IFA and neutralization tests were
      92% for consecutively grown isolates and 85% for all enterovirus isolates. The
      sensitivity of the IFA for the detection of viruses for which specific monoclonal
      antibodies were applied was 73% for polioviruses, 85% for coxsackieviruses type
      B, and 94% for echoviruses. Specificity was near 100% for polioviruses and
      coxsackieviruses type B and 94% for echoviruses. We conclude that IFA can be
      helpful as a preliminary test for serotype identification of enteroviruses. The
      results are most accurate when the test identifies the isolate as a poliovirus.

PMID- 9650929
TI  - Determination of types of Enterocytozoon bieneusi strains isolated from patients
      with intestinal microsporidiosis.
AB  - To determine the types of Enterocytozoon bieneusi strains associated with
      intestinal microsporidiosis, we developed a rapid and efficient approach for
      typing parasites obtained from stool specimens by PCR-restriction fragment length
      polymorphism (PCR-RFLP). Typing was based on DNA polymorphism of the ribosomal
      DNA internal transcribed spacer (ITS) region of E. bieneusi. RFLPs generated with
      two restriction enzymes (NlaIII and Fnu4HI) in PCR-amplified ITS products were
      used to classify strains into different lineages. This approach was successfully
      used to differentiate 78 strains that had been obtained from the stools of 65
      patients with intestinal microsporidiosis. Among the 78 strains, we found four
      genetically unrelated lineages, showing the genetic diversity of E. bieneusi.
      Type I strains of E. bieneusi were found in a majority of the samples, accounting
      for 51 (78%) of the 65 microsporidiosis cases. In contrast, type II, III, and IV
      strains were found in only 8 (12%), 3 (5%), and 3 (5%) cases, respectively. All
      strains of E. bieneusi we have tested so far fall into one of four different
      lineages, and this study shows that human intestinal microsporidiosis is most
      often associated with type I strains. PCR-RFLP analysis of the ITS region of E.
      bieneusi should be useful for epidemiological studies.

PMID- 9650930
TI  - International surveillance of bloodstream infections due to Candida species:
      frequency of occurrence and antifungal susceptibilities of isolates collected in
      1997 in the United States, Canada, and South America for the SENTRY Program. The
      SENTRY Participant Group.
AB  - An international program of surveillance of bloodstream infections (BSIs) in the
      United States, Canada, and South America between January and December 1997
      detected 306 episodes of candidemia in 34 medical centers (22 in the United
      States, 6 in Canada, and 6 in South America). Eighty percent of the BSIs were
      nosocomial and 50% occurred in patients hospitalized in an intensive care unit.
      Overall, 53.3% of the BSIs were due to Candida albicans, 15.7% were due to C.
      parapsilosis, 15.0% were due to C. glabrata, 7.8% were due to C. tropicalis, 2.0%
      were due to C. krusei, 0.7% were due to C. guilliermondii, and 5.8% were due to
      Candida spp. However, the distribution of species varied markedly by country. In
      the United States, 43.8% of BSIs were due to non-C. albicans species. C. glabrata
      was the most common non-C. albicans species in the United States. The proportion
      of non-C. albicans BSIs was slightly higher in Canada (47.5%), where C.
      parapsilosis, not C. glabrata, was the most common non-C. albicans species. C.
      albicans accounted for 40.5% of all BSIs in South America, followed by C.
      parapsilosis (38.1%) and C. tropicalis (11.9%). Only one BSI due to C. glabrata
      was observed in South American hospitals. Among the different species of Candida,
      resistance to fluconazole (MIC, > or = 64 microg/ml) and itraconazole (MIC, > or
      = 1.0 microg/ml) was observed with C. glabrata and C. krusei and was observed
      more rarely among other species. Isolates of C. albicans, C. parapsilosis, C.
      tropicalis, and C. guilliermondii were all highly susceptible to both fluconazole
      (99.4 to 100% susceptibility) and itraconazole (95.8 to 100% susceptibility). In
      contrast, 8.7% of C. glabrata isolates (MIC at which 90% of isolates are
      inhibited [MIC90], 32 microg/ml) and 100% of C. krusei isolates were resistant to
      fluconazole, and 36.9% of C. glabrata isolates (MIC90, 2.0 microg/ml) and 66.6%
      of C. krusei isolates were resistant to itraconazole. Within each species there
      were no geographic differences in susceptibility to fluconazole or itraconazole.

PMID- 9650931
TI  - Rapid detection of Chlamydia pneumoniae by PCR-enzyme immunoassay.
AB  - Chlamydia pneumoniae is an important human respiratory pathogen. Laboratory
      diagnosis of infection with this organism is difficult. To facilitate the
      detection of C. pneumoniae by PCR, an enzyme immunoassay (EIA) for analysis of
      PCR products was developed. Biotin-labeled PCR products generated from the 16S
      rRNA gene of C. pneumoniae were hybridized to a digoxigenin-labeled probe and
      then immobilized to streptavidin-coated microtiter plates. Bound PCR product
      probe hybrids were detected with antidigoxigenin peroxidase conjugate and a
      colorimetric substrate. This EIA was as sensitive as Southern blot hybridization
      for the detection of PCR products and 100 times more sensitive than visualization
      of PCR products on agarose gels. The diagnostic value of the PCR-EIA in
      comparison to cell culture was assessed in throat swab specimens from children
      with respiratory tract infections. C. pneumoniae was isolated from only 1 of 368
      specimens tested. In contrast, 15 patient specimens were repeatedly positive for
      C. pneumoniae by PCR and Southern analysis. All of these 15 specimens were also
      identified by PCR-EIA. Of the 15 specimens positive by 16S rRNA-based PCR, 13
      specimens could be confirmed by omp1-based PCR or direct fluorescent-antibody
      assay. Results of this study demonstrate that PCR is more sensitive than cell
      culture for the detection of C. pneumoniae. The EIA described here is a rapid,
      sensitive, and simple method for detection of amplified C. pneumoniae DNA.

PMID- 9650932
TI  - Algorithmic approach to high-throughput molecular screening for alpha interferon
      resistant genotypes in hepatitis C patients.
AB  - This study was designed to analyze the feasibility and validity of using Cleavase
      Fragment Length Polymorphism (CFLP) analysis as an alternative to DNA sequencing
      for high-throughput screening of hepatitis C virus (HCV) genotypes in a high
      volume molecular pathology laboratory setting. By using a 244-bp amplicon from
      the 5' untranslated region of the HCV genome, 61 clinical samples received for
      HCV reverse transcription-PCR (RT-PCR) were genotyped by this method. The
      genotype frequencies assigned by the CFLP method were 44.3% for type 1a, 26.2%
      for 1b, 13.1% for type 2b, and 5% type 3a. The results obtained by nucleotide
      sequence analysis provided 100% concordance with those obtained by CFLP analysis
      at the major genotype level, with resolvable differences as to subtype
      designations for five samples. CFLP analysis-derived HCV genotype frequencies
      also concurred with the national estimates (N. N. Zein et al., Ann. Intern. Med.
      125:634-639, 1996). Reanalysis of 42 of these samples in parallel in a different
      research laboratory reproduced the CFLP fingerprints for 100% of the samples.
      Similarly, the major subtype designations for 19 samples subjected to different
      incubation temperature-time conditions were also 100% reproducible. Comparative
      cost analysis for genotyping of HCV by line probe assay, CFLP analysis, and
      automated DNA sequencing indicated that the average cost per amplicon was lowest
      for CFLP analysis, at $20 (direct costs). On the basis of these findings we
      propose that CFLP analysis is a robust, sensitive, specific, and an economical
      method for large-scale screening of HCV-infected patients for alpha interferon
      resistant HCV genotypes. The paper describes an algorithm that uses as a reflex
      test the RT-PCR-based qualitative screening of samples for HCV detection and also
      addresses genotypes that are ambiguous.

PMID- 9650933
TI  - Identification and molecular characterization of beta-hemolytic streptococci
      isolated from harbor porpoises (Phocoena phocoena) of the North and Baltic Seas.
AB  - The present study was designed to identify and comparatively investigate 35 beta
      hemolytic streptococci isolated from stranded harbor porpoises or from animals
      caught in fishing nets of the North and Baltic seas. According to biochemical and
      serological data and to lectin agglutination tests with the lectin of Arachis
      hypogaea, all 35 isolates could be classified in Lancefield's serological group L
      and could be identified as Streptococcus dysgalactiae subsp. dysgalactiae. All 35
      group L streptococci were uniformly sensitive to most of the antibiotics tested.
      To further analyze the epidemiological relationship, the isolates were subjected
      to macrorestriction analysis of their chromosomal DNA by pulsed-field gel
      electrophoresis. Digestion of the chromosomal DNA with the restriction enzymes
      SmaI and ApaI revealed that most of the group L streptococci seemed to be
      apparently identical or related. These results indicate that one clone or at
      least related group L streptococcal clones play an important role for infections
      of harbor porpoises of the North and Baltic seas. This might possibly be caused
      by a direct transfer of the bacteria from animal to animal.

PMID- 9650934
TI  - Effects of different test conditions on MICs of food animal growth-promoting
      antibacterial agents for enterococci.
AB  - The influence of the addition of sheep blood to Mueller-Hinton II agar and the
      effects of aerobic incubation with or without CO2 and of anaerobic incubation
      were tested with bacitracin, tylosin, avoparcin, virginiamycin, avilamycin,
      narasin, and flavomycin on enterococci. The antibacterial activity of bambermycin
      (Flavomycin) was strongly inhibited by the addition of blood, except with the
      species Enterococcus faecium, Enterococcus mundtii, Enterococcus hirae,
      Enterococcus casseliflavus, and Enterococcus gallinarum, which were not
      susceptible to this antibiotic on blood-free medium. With all other
      antimicrobials except avoparcin and tylosin, the presence of blood resulted in
      MIC increases of 1 to 3 log2 differences. Incubation in aerobic or anaerobic
      atmospheres enriched with CO2 lowered the susceptibility of enterococci to
      tylosin and increased their susceptibility to avilamycin, narasin, and avoparcin.
      This effect was most pronounced in tests on blood-free media. Results of
      susceptibility tests incubated under anaerobiosis and in a CO2-enriched
      atmosphere did not differ. For all enterococcal species, the preferred conditions
      for testing the susceptibility are Mueller-Hinton II medium supplemented with
      blood and incubation in a CO2-enriched atmosphere. However, when only E. faecium
      and Enterococcus faecalis are being tested, Mueller-Hinton II medium without
      blood incubated aerobically gives satisfactory results.

PMID- 9650936
TI  - Use of lambda phage DNA as a hybrid internal control in a PCR-enzyme immunoassay
      to detect Chlamydia pneumoniae.
AB  - An inherent problem in the diagnostic PCR assay is the presence of ill-defined
      inhibitors of amplification which may cause false-negative results. Addition of
      an amplifiable fragment of foreign DNA in the PCR to serve as a hybrid internal
      control (HIC) would allow for a simple way to identify specimens containing
      inhibitors. Two oligonucleotide hybrid primers were synthesized to contain
      nucleic acid sequences of the Chlamydia pneumoniae 16S rRNA primers in a position
      flanking two primers that target the sequences of a 650-bp lambda phage DNA
      segment. By using the hybrid primers, hybrid DNA comprising a large sequence of
      lambda phage DNA flanked by short pieces of chlamydia DNA was subsequently
      generated by PCR, cloned into a plasmid vector, and purified. Plasmids containing
      the hybrid DNA were diluted and used as a HIC by adding them to each C.
      pneumoniae PCR test. Consequently, C. pneumoniae primers were able to amplify
      both chlamydia DNA and the HIC DNA. The production of a 689-bp HIC DNA band on an
      acrylamide gel indicated that the specimen contained no inhibitors and that
      internal conditions were compatible with PCR. Subsequently, a biotinylated RNA
      probe for the HIC was transcribed from a nested sequence of the HIC and was used
      for its hybridization. Detection of the HIC DNA-RNA hybrid was achieved by enzyme
      immunoassay (EIA). This PCR-EIA system with a HIC was initially tested with 12
      previously PCR-positive and 14 previously PCR-negative specimens. Of the 12 PCR
      positive specimens, 11 were reconfirmed as positive; 1 had a negative HIC value,
      indicating inhibition. Of the 14 previously PCR-negative specimens, 13 were
      confirmed as true negative; 1 had a negative HIC value, indicating inhibition.
      The assay was then used with 237 nasopharyngeal specimens from patients with
      pneumonia. Twenty-one of 237 (8.9%) were positive for C. pneumoniae, and 42
      (17.7%) were found to inhibit the PCR. Specimens showing inhibitory activity were
      diluted 1:10 and were retested. Ten specimens were still inhibitory to the PCR
      and required further DNA purification. No additional positive samples were
      detected and 3 nasopharyngeal specimens remained inhibitory to PCR.
      Coamplification of a HIC DNA can help confirm true-negative PCR results by ruling
      out the presence of inhibitors of DNA amplification.

PMID- 9650935
TI  - Antigenic and molecular characterization of wild type 1 poliovirus causing
      outbreaks of poliomyelitis in Albania and neighboring countries in 1996.
AB  - Mass vaccination has led poliomyelitis to become a rare disease in a large part
      of the world, including Western Europe. However, in the past 20 years wild
      polioviruses imported from countries where polio is endemic have been responsible
      for outbreaks in otherwise polio-free European countries. We report on the
      characterization of poliovirus isolates from a large outbreak of poliomyelitis
      that occurred in Albania in 1996 and that also spread to the neighboring
      countries of Yugoslavia and Greece. The epidemics involved 145 subjects, mostly
      young adults, and caused persisting paralysis in 87 individuals and 16 deaths.
      The agent responsible for the outbreak was isolated from 74 patients and was
      identified as wild type 1 poliovirus by both immunological and molecular methods.
      Sequence analysis of the genome demonstrated the involvement of a single virus
      strain throughout the epidemics, and genotyping analysis showed 95% homology of
      the strain with a wild type 1 poliovirus strain isolated in Pakistan in 1995.
      Neutralization assays with both human sera and monoclonal antibodies were
      performed to analyze the antigenic structure of the epidemic strain, suggesting
      its peculiar antigenic characteristics. The presented data underline the current
      risks of outbreaks due to imported wild poliovirus and emphasize the need to
      improve vaccination efforts and also the need to implement surveillance in
      countries free of indigenous wild poliovirus.

PMID- 9650937
TI  - Blood cultures positive for coagulase-negative staphylococci: antisepsis,
      pseudobacteremia, and therapy of patients.
AB  - A blood culture cohort study investigating issues related to isolation of
      coagulase-negative staphylococci (CoNS) and other skin microflora is reported.
      Data were collected over 12 weeks to determine the incidence of significant CoNS
      bacteremia versus that of pseudobacteremia (contaminants) and to evaluate drug
      therapy in patients with cultures positive for CoNS. In addition, the
      effectiveness of 0.2% chlorine peroxide as a bactericidal disinfectant was
      compared to that of 10% providone iodine. A total of 3,276 cultures of blood from
      1,433 patients were evaluated in the study. Eighty-nine cultures were positive
      for skin flora, with 81 of 89 (91%) involving CoNS. The incidence of significant
      CoNS bacteremia was 20 of 81 (24.7%), that of indeterminate bacteremia was 10 of
      81 (12.3%), and that of contamination was 59 of 81 (72.8%). The incidence of
      significant bacteremia involving CoNS was double the 10 to 12% rate based on
      previous estimations at our institutions. In tests with the two bactericidal
      disinfectants, 22 of 1,639 cultures (1.3%) in the chlorine peroxide group versus
      37 of 1,637 (2.3%) in the providone iodine group were considered contaminated (P
      = 0.065). Rates of contamination for venipuncture versus catheter collection were
      not significantly different (P = 0.46). The overall contamination rate was 59 of
      3,276 (1.8%), which is consistent with the lower end of published quality
      assurance benchmark standards. The low rate was believed to be due to the
      professional phlebotomy staff in our institutions. There was excellent agreement
      between retrospective analysis by reviewers, when formal criteria were used, and
      the attending physicians' intuitive clinical impressions in the classification of
      significant bloodstream infections (100% agreement) or contamination (95%
      agreement). However, physicians still used antimicrobial agents to treat nearly
      one-half of the patients with contaminated blood cultures, with vancomycin being
      misused in 34% of patients. In addition, 10% of patients with significant
      bacteremia were treated with inappropriate agents. There were no significant
      adverse events or prolonged hospital stays due to the unnecessary use of
      vancomycin; however, the additional costs of treating patients whose cultures
      contained CoNS contaminants was estimated to be $1,000 per patient. Measures to
      limit the unnecessary use of vancomycin (and other agents) are important.

PMID- 9650938
TI  - Molecular characterization of vancomycin-resistant enterococci from hospitalized
      patients and poultry products in The Netherlands.
AB  - Vancomycin-resistant enterococci (VRE) pose an emerging health risk, but little
      is known about the precise epidemiology of the genes coding for vancomycin
      resistance. To determine whether the bacterial flora of consumer poultry serves
      as a gene reservoir, the level of contamination of poultry products with VRE was
      determined. VRE were genotyped by pulsed-field gel electrophoresis (PFGE), and
      transposon structure mapping was done by PCR. The vanX-vanY intergenic regions of
      several strains were further analyzed by sequencing. A total of 242 of 305 (79%)
      poultry products were found to be contaminated with VRE. Of these VRE, 142 (59%)
      were high-level-vancomycin-resistant Enterococcus faecium strains (VREF). PFGE
      revealed extensive VREF heterogeneity. Two genotypes were found nationwide on
      multiple occasions: type A (22 of 142 VREF [15%]) and type B (14 of 142 VREF
      [10%]). No PFGE-deduced genetic overlap was found when VREF from humans were
      compared with VREF from poultry. Two vanA transposon types were identified among
      poultry strains. In 59 of 142 (42%) of the poultry VREF, the size of the
      intergenic region between vanX and vanY was approximately 1,300 bp. This
      transposon type was not found in human VREF. In contrast, all human strains and
      83 of 142 (58%) of the poultry VREF contained an intergenic region 543 bp in
      size. Sequencing of this 543-bp intergenic vanX-vanY region demonstrated full
      sequence conservation. Though preliminary, these data suggest that dissemination
      of the resistance genes carried on transposable elements may be of greater
      importance than clonal dissemination of resistant strains. This observation is
      important for developing strategies to control the spread of glycopeptide
      resistance.

PMID- 9650939
TI  - Extremely high prevalence of nasopharyngeal carriage of penicillin-resistant
      Streptococcus pneumoniae among children in Kaohsiung, Taiwan.
AB  - Resistance (intermediate and high) to penicillin among Streptococcus pneumoniae
      strains is an emerging problem worldwide. From 1995 to 1997, isolates of S.
      pneumoniae not susceptible to penicillin were seen with increasing frequency from
      blood, cerebrospinal fluid, pleural fluid, and middle ear fluid from pediatric
      patients at the Veterans General Hospital-Kaohsiung. To determine the prevalence
      of carriage of these penicillin-nonsusceptible S. pneumoniae isolates, we
      obtained nasopharyngeal swab specimens from 2,905 children (ages, 2 months to 7
      years) attending day-care centers or kindergartens or seen in our outpatient
      clinic. S. pneumoniae was isolated from 611 children, and 584 strains were
      available for analysis. The oxacillin disc test was used as a screening test to
      evaluate penicillin susceptibility. The MICs of 11 antibiotics (penicillin,
      cefaclor, cefuroxime, ceftriaxone, cefotaxime, imipenem, chloramphenicol,
      clarithromycin, rifampin, vancomycin, and teicoplanin) were determined by the E
      test. Only 169 (29%) of the strains were susceptible to penicillin; 175 (30%)
      strains were intermediately resistant and 240 (41%) were highly resistant. The
      isolates also demonstrated high rates of resistance to other beta-lactams (46%
      were resistant to cefaclor, 45% were resistant to cefuroxime, 45% were resistant
      to ceftriaxone, 31% were resistant to cefotaxime, and 46% were resistant to
      imipenem). The rate of resistance to macrolide antimicrobial agents was
      strikingly high; 95% of the isolates were not susceptible to clarithromycin.
      However, 97% were susceptible to rifampin and 100% were susceptible to the two
      glycopeptides (vancomycin and teicoplanin). While reports of penicillin-resistant
      S. pneumoniae increased worldwide through the 1980s, the high prevalence (71%) of
      resistance reported here is astonishing. Surveillance of nasopharyngeal swab
      specimen cultures may provide useful information on the prevalence of
      nonsusceptible strains causing invasive disease. Such information could be used
      to guide therapy of pneumococcal infections.

PMID- 9650940
TI  - Survival of Acinetobacter baumannii on dry surfaces: comparison of outbreak and
      sporadic isolates.
AB  - Acinetobacter spp. are important nosocomial pathogens reported with increasing
      frequency in outbreaks of cross-infection during the past 2 decades. The majority
      of such outbreaks are caused by Acinetobacter baumannii. To investigate whether
      desiccation tolerance may be involved in the ability of certain strains of A.
      baumannii to cause hospital outbreaks, a blind study was carried out with 39
      epidemiologically well-characterized clinical isolates of A. baumannii for which
      survival times were determined under simulated hospital conditions. The survival
      times on glass coverslips of 22 strains isolated from eight well-defined hospital
      outbreaks in a German metropolitan area were compared with the survival times of
      17 sporadic strains not involved in outbreaks but rather isolated from inpatients
      in the same geographic area. All sporadic isolates have been shown by pulsed
      field gel electrophoresis to represent different strain types. There was no
      statistically significant difference between the survival times of sporadic
      strains of A. baumannii and outbreak strains (27.2 versus 26.5 days,
      respectively; P < or = 0.44) by the Wilcoxon-Mann-Whitney test. All investigated
      A. baumannii strains, irrespective of their areas of endemicity or epidemic
      occurrence, have the ability to survive for a long time on dry surfaces.
      Antimicrobial susceptibility testing showed that A. baumannii outbreak strains
      were significantly more resistant to various broad-spectrum antimicrobial agents
      than sporadic strains. Both desiccation tolerance and multidrug resistance may
      contribute to their maintenance in the hospital setting and may explain in part
      their propensity to cause prolonged outbreaks of nosocomial infection.

PMID- 9650941
TI  - Epidemiological and environmental investigations of Legionella pneumophila
      infection in cattle and case report of fatal pneumonia in a calf.
AB  - A fatal pneumonia due to Legionella pneumophila was diagnosed in a young calf
      reared in a dairy herd located in northern Italy. Clinical symptoms consisted of
      watery diarrhea, hyperthermia, anorexia, and severe dyspnea. The pathological and
      histological findings were very similar to those observed in human legionellosis.
      Legionella pneumophila serogroup 1 (SG1) and SG10 were isolated from the calfs
      lung, and L. pneumophila SG1 was isolated from the calfs liver. L. pneumophila
      SG1 was also demonstrated in the lung tissue by immunofluorescence and
      immunohistochemical examinations. Nine of 10 L. pneumophila SG1 isolates belonged
      to the Olda subtype, and 1 belonged to the Camperdown subtype. A very low
      prevalence of antibodies to Legionella was detected in cows and calves reared in
      the same herd. Cultures of aqueous sediment of an old electric water heater which
      supplied hot water for the feeding of the calves yielded L. pneumophila SG1. Four
      of the colonies tested belonged to the Olda subtype. Ten clinical and four
      environmental isolates were examined for the presence of plasmids. Nine of them
      were also examined by pulsed-field gel electrophoresis assay, and the same
      patterns were found for L. pneumophila SG1 Olda strains isolated from the calf
      and from the electric heater. This is the first report of a documented case of a
      naturally occurring Legionella pneumonia in an animal. Cattle probably act as
      accidental hosts for legionellae, much the same as humans.

PMID- 9650942
TI  - Evaluation of the VITEK 2 system for rapid identification of medically relevant
      gram-negative rods.
AB  - The new VITEK 2 system (bioMerieux) was evaluated at two independent sites with
      the identification card for gram-negative bacilli (ID-GNB card). Of the 845
      strains tested, which represented 70 different taxa belonging to either the
      family Enterobacteriaceae or the nonenteric bacilli, 716 (84.7%) were correctly
      identified at the species level. Thirty-two (3.8%) additional strains were
      identified to the species level after the performance of simple, rapid manual
      tests (oxidase, hemolysis, indole reaction, motility, and pigmentation). For 80
      (9.5%) strains, these additional tests did not lead to an identification at the
      species level but the correct species identification was given among the
      organisms listed. Only 7 (0.8%) strains were misidentified, and 10 (1.2%) were
      not identified. Mistakes were randomly distributed over different taxa. Due to
      the new, more sensitive fluorescence-based technology of the VITEK 2 system,
      final results were available after 3 h. Since our evaluation was mainly a stress
      test, it is predicted that the VITEK 2 system in conjunction with the ID-GNB card
      would perform well under conditions of a routine clinical laboratory in
      identifying members of the family Enterobacteriaceae and selected species of
      nonenteric bacteria. This system is a promising, highly automated new tool for
      the rapid identification of gram-negative bacilli from human clinical specimens.

PMID- 9650943
TI  - Molecular epidemiology of Stenotrophomonas maltophilia isolated from clinical
      specimens from patients with cystic fibrosis and associated environmental
      samples.
AB  - Stenotrophomonas maltophilia was isolated from the respiratory tracts of 41 (25%)
      of 163 children attending our pediatric cystic fibrosis unit between September
      1993 and December 1995. The extents of S. maltophilia contamination of
      environmental sites frequented by these patients were investigated with a
      selective medium incorporating vancomycin, imipenem, and amphotericin B. Eighty
      two isolates of S. maltophilia were cultured from 67 different environmental
      sites sampled between January and July 1996. The organism was widespread in the
      home environment, with 20 (36%) and 25 (42%) of sampled sites positive in the
      homes of colonized and noncolonized patients, respectively. In the nosocomial
      setting, it was isolated from 18 (32%) sites in the hospital ward and from 4
      (17%) sites in the outpatient clinic area. The most common sites of contamination
      were sink drains, faucets, and other items frequently in contact with water. All
      environmental and clinical isolates were genotyped with enterobacterial
      repetitive intergenic consensus sequences as primers. A total of 33 of the 41
      patients were colonized with unique strains, and four pairs of patients shared
      strains. Further characterization by pulsed-field gel electrophoresis after
      digestion with XbaI found that there was no evidence of patient-to-patient
      transmission; however, there was some evidence that a small number of patients
      may have acquired the organism from the hospital environment. Resampling of
      environmental sites in the hospital ward in January 1997 revealed evidence of
      genetic drift, complicating the accurate determination of environmental sources
      for clinical strains. The source of the majority of S. maltophilia strains
      colonizing the respiratory tracts of these patients with cystic fibrosis remained
      uncertain but may have represented multiple, independent acquisitions from a
      variety of environmental sites both within and outside the hospital.

PMID- 9650944
TI  - Cytoplasmic, nuclear, and platelet autoantibodies in human granulocytic
      ehrlichiosis patients.
AB  - Serum samples from patients with confirmed human granulocytic ehrlichiosis (HGE)
      were tested for cytoplasmic, nuclear, and platelet autoantibodies and rheumatoid
      factor. The indirect fluorescence antinuclear antibody test on Hep-2 cells
      demonstrated antinuclear titers of > or = 40 and > or = 160 in 44 and 10%,
      respectively, of serum samples from HGE patients. Two patients (4%) had
      anticytoplasmic (mitochondrial and spindle apparatus) antibodies with a titer of
      80 and two patients (4%) had anticytoplasmic (mitochondrial) antibodies with a
      titer of 160 or greater. Flow cytometry was used to demonstrate antiplatelet
      antibodies in 80% of first serum samples from HGE patients. Rheumatoid factor was
      not detected. Nuclear and cytoplasmic autoantibodies are a major cause of
      interference when the indirect fluorescence antibody test is used to detect
      fluorescence of morulae in Ehrlichia-infected equine neutrophils or HL-60
      promyelocytes. Antiplatelet antibodies may contribute to the profound
      thrombocytopenia which is a characteristic laboratory feature during the acute
      phase of HGE infection. Whether autoantibodies precede infection or are caused by
      immune activation of HGE deserves further study.

PMID- 9650945
TI  - Comparison of the ABI 7700 system (TaqMan) and competitive PCR for quantification
      of IS6110 DNA in sputum during treatment of tuberculosis.
AB  - Mycobacterium tuberculosis can persist in sputum for long periods of time after
      the initiation of antituberculosis chemotherapy. The purpose of this study was to
      determine whether quantitative estimates of M. tuberculosis DNA in sputum
      correlate with the numbers of viable bacilli and thus measure the therapeutic
      response of patients during treatment. Two methods of M. tuberculosis DNA
      quantification were examined by using DNA isolated from sputum specimens serially
      collected during the course of chemotherapy. A competitive PCR assay was compared
      to an automated system of real-time quantification with the ABI Prism 7700
      Sequence Detection System (TaqMan). The ABI 7700 system uses standard PCR in
      conjunction with a fluorogenic probe in which the intensity of fluorescence is
      proportional to the amount of target DNA present. The results showed that both
      PCR systems are reproducible and accurate. The amounts of M. tuberculosis DNA
      quantified in sputum corresponded well with the numbers of acid-fast bacilli
      (AFB) counted by microscopy. Before initiation of antituberculosis therapy,
      measures of AFB, M. tuberculosis DNA, and cultivable bacilli were similar,
      suggesting that quantification of DNA is a good method for measuring the initial
      bacillary load. However, the rate of disappearance of both AFB and M.
      tuberculosis DNA did not correlate with the decline in cultivable bacilli in the
      specimen; therefore, these tests are not appropriate for monitoring treatment
      efficacy.

PMID- 9650946
TI  - Comparison of three molecular assays for rapid detection of rifampin resistance
      in Mycobacterium tuberculosis.
AB  - Multidrug-resistant Mycobacterium tuberculosis (MDR-TB) is an emerging problem of
      great importance to public health, with higher mortality rates than drug
      sensitive TB, particularly in immunocompromised patients. MDR-TB patients require
      treatment with more-toxic second-line drugs and remain infectious for longer than
      patients infected with drug-sensitive strains, incurring higher costs due to
      prolonged hospitalization. It is estimated that 90% of United Kingdom rifampin
      resistant isolates are also resistant to isoniazid, making rifampin resistance a
      useful surrogate marker for multidrug resistance and indicating that second- and
      third-line drugs to which these isolates are susceptible are urgently required.
      Resistance in approximately 95% of rifampin-resistant isolates is due to
      mutations in a 69-bp region of the rpoB gene, making this a good target for
      molecular genotypic diagnostic methods. Two molecular assays, INNO-LiPA Rif.TB
      (Innogenetics, Zwijndrecht, Belgium) and MisMatch Detect II (Ambion, Austin,
      Tex.), were performed on primary specimens and cultures to predict rifampin
      resistance, and these methods were compared with the resistance ratio method. A
      third method, the phenotypic PhaB assay, was also evaluated in comparison to
      cultures in parallel with the genotypic assays. In an initial evaluation 16 of
      16, 15 of 16, and 16 of 16 rifampin-resistant cultures (100, 93.8, and 100%,
      respectively), were correctly identified by line probe assay (LiPA), mismatch
      assay, and PhaB assay, respectively. Subsequently 38 sputa and bronchealveolar
      lavage specimens and 21 isolates were received from clinicians for molecular
      analysis. For the 38 primary specimens the LiPA and mismatch assay correlated
      with culture and subsequent identification and susceptibility tests in 36 and 38
      specimens (94.7 and 100%), respectively. For the 21 isolates submitted by
      clinicians, both assays correlated 100% with routine testing.

PMID- 9650947
TI  - Evaluation of intestinal protozoan morphology in human fecal specimens preserved
      in EcoFix: comparison of Wheatley's trichrome stain and EcoStain.
AB  - As a result of disposal problems related to the use of mercury compounds, many
      laboratories have switched from mercuric chloride-based Schaudinn's and polyvinyl
      alcohol (PVA) stool preservatives to other, non-mercury-based preservatives. A
      comparison of organism recoveries and morphologies of the intestinal protozoa was
      undertaken with PVA containing the EcoFix zinc-based Schaudinn's preservative
      (Meridian Diagnostics, Inc.); both Wheatley's modification of Gomori's trichrome
      stain (WT) and EcoStain (ES) were used to stain 51 human fecal specimens.
      Morphology, clarity of nuclear and cytoplasmic detail, overall color differences,
      and the ease or difficulty in detecting intestinal protozoa in fecal debris were
      assessed for the two permanent stained smears. Overall, organism morphology of
      the intestinal protozoa stained with WT and that of protozoa stained with ES were
      not equal in nuclear and cytoplasmic detail or range of color. However, the same
      organisms were identified in stained fecal smears with either WT or ES, with the
      exception of situations in which organism numbers were characterized as rare.
      Included were 67 protozoan challenges (number of organisms): Entamoeba
      histolytica-Entamoeba dispar (5), Entamoeba coli (9), Entamoeba hartmanni (6),
      Endolimax nana (12), Iodamoeba butschlii (8), Blastocystis hominis (19), Giardia
      lamblia (6), Dientamoeba fragilis (2), yeast (2), and leukocytes (2). Five
      specimens were negative for parasites but contained fecal debris that was
      compared for morphologic detail and color range. The ES produces a more gray
      green monotone with very little pink or red tone; contrast among the various
      colors is less than that seen with WT. Stain intensity for all organisms was
      acceptable, and there were no problems with stain deposition. The quality of the
      protozoan morphology with ES was often comparable to that with WT (36 of 67
      [53.7%]) and, in some cases, better (24 of 67 [35.8%]). Organisms on the WT
      stained smear exhibited better morphology in a few instances (4 of 67 [6%]), and
      in three instances, there were discrepant organism numbers.

PMID- 9650948
TI  - Genetic diversity among strains of Moraxella catarrhalis: analysis using multiple
      DNA probes and a single-locus PCR-restriction fragment length polymorphism
      method.
AB  - Moraxella (Branhamella) catarrhalis, a causative agent of otitis media,
      sinusitis, and exacerbation of bronchitis, has acquired widespread ability to
      produce beta-lactamase and can be nosocomially transmitted. The typing methods
      used in epidemiological analyses of M. catarrhalis are not optimal for genetic
      analyses. Two methods, a multiple-locus Southern blot (SB) method and a single
      locus PCR-restriction fragment length polymorphism (RFLP) method, were developed
      and used to assess genetic diversity and potential clinical and geographic
      relationships in M. catarrhalis. Nine randomly cloned M. catarrhalis DNA
      fragments were used as probes of SBs containing DNA from 54 geographically and
      clinically diverse strains. For comparison, a PCR-RFLP method was developed as a
      quick, inexpensive, and discriminating alternative. A highly variable 3.7-kb
      genomic region (M46) was cloned and sequenced, and 3.5 kb of the cloned DNA was
      targeted for PCR amplification. DNAs from the 54 strains were subjected to PCR
      RFLP. SB analysis distinguished all strains that had no apparent epidemiological
      linkage (40 of 54), and PCR-RFLP distinguished fewer strains (21 of 54).
      Epidemiologically linked strains appeared genetically identical by both methods.
      PCR-RFLP was compared to pulsed-field gel electrophoresis (PFGE) for 8 of the 54
      strains and 23 additional strains. PCR-RFLP distinguished fewer strains than PFGE
      typing (16 of 31 versus 20 of 31 strains), but PCR-RFLP was more useful for
      inferring interstrain relatedness. Separate cluster analyses of multilocus SB and
      single locus PCR-RFLP data showed high genetic diversity within and across
      geographic locations and clinical presentations. The resultant dendrograms were
      not entirely concordant, but both methods often gave similar strain clusters at
      the terminal branches. High genetic diversity, nonconcordance of cluster analyses
      from different genetic loci, and shared genotypes among epidemiologically linked
      strains support a hypothesis of high recombination relative to spread of clones.
      Single-locus PCR-RFLP may be suitable for short-term epidemiological studies, but
      the SB data demonstrate that greater strain discrimination may be obtained by
      sampling variation at multiple genomic sites.

PMID- 9650949
TI  - Detection of Mycoplasma hyopneumoniae in bronchoalveolar lavage fluids of pigs by
      PCR.
AB  - In the present investigation we developed a method for the detection of
      Mycoplasma hyopneumoniae in bronchoalveolar lavage fluid (BALF) of pigs by PCR
      with a primer pair flanking a DNA fragment of 853 bp specific for M.
      hyopneumoniae. Several methods were tested to eliminate the amplification
      inhibitors present in BALFs. The best results were obtained by the extraction of
      the DNA from the BALFs. By the PCR performed with the extracted DNA, 10(2) CFU of
      M. hyopneumoniae could be detected in 1 ml of BALF from specific-pathogen-free
      swine experimentally inoculated with M. hyopneumoniae. DNA from 11 other
      mycoplasma species and 17 cell-walled bacterial species colonizing the
      respiratory tracts of pigs was not amplified. In a field study BALFs from 40 pigs
      from farms with a history of chronic pneumonia were tested for M. hyopneumoniae
      by cultivation and by PCR (i) with BALFs incubated in Friis medium and (ii) with
      DNA extracted from the BALFs. In addition, PCR was performed with postmortem lung
      washings from 19 of the 40 pigs, and immunofluorescence tests were carried out
      with sections of lungs from 18 of the 40 pigs. M. hyopneumoniae could not be
      detected in 18 of the 40 pigs by any of the five methods tested. The remaining 22
      pigs showed a positive reaction by the PCR with DNA extracted from the BALFs and
      variable positive reactions by the other tests. A complete correspondence could
      be observed between the immunofluorescence test result and the result of PCR with
      DNA. The investigation shows that the PCR with DNA extracted from BALFs is a
      suitable technique for the sensitive and specific in vivo detection of M.
      hyopneumoniae.

PMID- 9650950
TI  - Single-step multiplex PCR assay for characterization of New World Leishmania
      complexes.
AB  - We have developed a PCR assay for one-step differentiation of the three complexes
      of New World Leishmania (Leishmania braziliensis, Leishmania mexicana, and
      Leishmania donovani). This multiplex assay is targeted to the spliced leader RNA
      (mini-exon) gene repeats of these organisms and can detect all three complexes
      simultaneously, generating differently sized products for each complex. The assay
      is specific to the Leishmania genus and does not recognize related kinetoplastid
      protozoa, such as Trypanosoma cruzi, Trypanosoma brucei, and Crithidia
      fasciculata. It correctly identified Leishmania species with a broad geographic
      distribution in Central and South America. The sensitivity of the PCR
      amplification ranged from 1 fg to 10 pg of DNA (0.01 to 100 parasites), depending
      on the complex detected. Crude extracts of cultured parasites, prepared simply by
      boiling diluted cultures, served as excellent templates for amplification. Crude
      preparations of clinical material were also tested. The assay detected L.
      braziliensis in dermal scrapings from cutaneous leishmanial lesions, Leishmania
      chagasi in dermal scrapings of atypical cutaneous leishmaniasis, and L. mexicana
      from lesion aspirates from infected hamsters. We have minimized the material
      requirements and maximized the simplicity, rapidity, and informative content of
      this assay to render it suitable for use in laboratories in countries where
      leishmaniasis is endemic. This assay should be useful for rapid in-country
      identification of Leishmania parasites, particularly where different Leishmania
      complexes are found in the same geographical area.

PMID- 9650951
TI  - Novel method for processing respiratory specimens for detection of mycobacteria
      by using C18-carboxypropylbetaine: blinded study.
AB  - A novel method for processing respiratory specimens to improve culture and acid
      fast staining of mycobacteria is introduced. This new method utilized N,N
      dimethyl-N-(n-octadecyl)-N-(3-carboxypropyl)ammonium inner salt (Chemical
      Abstract Service no. 78195-27-4), also known as C18-carboxypropylbetaine (CB-18).
      In a blinded, five-center study, CB-18-based processing was compared to the
      standard method combining NALC and NaOH (NALC/NaOH). A total of 573 respiratory
      specimens were tested. Individual specimens were split approximately equally; the
      host institutions processed half of each specimen by the NALC/NaOH method, while
      the other half was processed with CB-18 at Quest Diagnostics--Baltimore. A total
      of 106 specimens were culture positive for acid-fast bacilli (AFB). Replacement
      of the primary decontamination agent with CB-18 caused changes in all diagnostic
      parameters. Aggregate culture sensitivity improved by approximately 43% (P <
      0.01), and smear sensitivity improved by approximately 58% (P < 0.01). The
      sensitivity of smear relative to that of M. tuberculosis isolates exceeded 93% (P
      < 0.01) when specimens were processed with CB-18. The average times to a positive
      result were reduced by 7.3 days in liquid culture (P < 0.01) and 5.3 days on
      solid media (P < 0.05); however, the CB-18 method had a 20.8% contamination rate
      in liquid culture versus a rate of approximately 7.5% with NALC/NaOH processing.
      There were also unusual reductions in liquid culture sensitivity and smear
      specificity among CB-18-processed specimens. The characteristics of the latter
      parameters suggested that refinement of the CB-18 processing method should allow
      further improvements in culture sensitivity. This study showed that the CB-18
      method has the potential to improve both smear and culture detection for these
      important human pathogens.

PMID- 9650952
TI  - Processing respiratory specimens with C18-carboxypropylbetaine: development of a
      sediment resuspension buffer that contains lytic enzymes to reduce the
      contamination rate and lecithin to alleviate toxicity.
AB  - The C18-carboxypropylbetaine (CB-18) procedure for processing respiratory
      specimens for the detection of mycobacteria was shown to provide significant
      increases in sensitivity by smear and culture. However, the procedure also
      produced increased contamination, a loss in liquid culture sensitivity, and a
      reduction in smear specificity. Because of these observations, the toxicity of CB
      18 and the nature of the contamination were characterized. Preincubation in 1 mM
      CB-18 impacted viability in a time-dependent fashion, but the magnitude of the
      loss was species and isolate dependent. Mycobacterium tuberculosis isolates were
      the most susceptible, losing 20 to 30% of the CFU within 30 min and 30 to 60%
      after 3 h, whereas Mycobacterium avium and Mycobacterium fortuitum isolates were
      unaffected by CB-18. In liquid culture, when the concentration of CB-18 exceeded
      5 microg/ml, there was an impact on growth characteristics for the most
      susceptible M. tuberculosis isolate. In contrast, M. fortuitum isolates were able
      to grow in 100 microg of CB-18 per ml. In liquid culture, the deleterious effects
      of CB-18 were enhanced in the presence of antibiotics, whereas growth on solid
      media was not similarly affected. Supplementation of the resuspension buffer with
      0.15% lecithin alleviated toxicity. Initial attempts to modify the CB-18
      procedure to control contamination incorporated acids or alkalis; however, losses
      in culture sensitivity occurred. Studies to identify these contaminants led to
      the development of a sediment resuspension buffer that contained lytic enzymes to
      combat contamination and lecithin to alleviate toxicity. This formulation
      included lysozyme, zymolyase, and Cytophaga and Trichoderma extracts and was seen
      to reduce contamination to acceptable levels (<5%).

PMID- 9650953
TI  - Recombinant hepatitis A virus antigen: improved production and utility in
      diagnostic immunoassays.
AB  - Hepatitis A virus (HAV) immunoassays use cell culture-derived HAV antigen to
      detect HAV-specific antibodies. The current method of production of HAV antigen
      in tissue culture is time-consuming and expensive. We previously expressed the
      HAV open reading frame in recombinant vaccinia viruses (rV-ORF). The recombinant
      HAV polyprotein was accurately processed and was assembled into subviral
      particles. These particles were bound by HAV-neutralizing antibodies and were
      able to elicit antibodies which were detected by commercial immunoassays. The
      present investigation compared the production of HAV antigen by standard tissue
      culture methods to the production of HAV antigen with the recombinant vaccinia
      virus system. In addition, HAV and rV-ORF antigens were assessed for their
      utility in diagnostic immunoassays. Serum or plasma samples from HAV antibody
      positive and antibody-negative individuals were evaluated by immunoassay that
      used either HAV or rV-ORF antigen. All samples (86 of 86) in which HAV antibody
      was detected by a commercial enzyme-linked immunosorbent assay (ELISA) also
      tested positive by the recombinant antigen-based immunoassay (VacRIA). Similarly,
      all samples (50 of 50) that were HAV antibody negative also tested negative by
      the VacRIA. The lower limit of detection of HAV antibody was similar among
      immunoassays with either HAV or rV-ORF antigen. Thus, in the population studied,
      the sensitivity and specificity of the VacRIA were equivalent to those of the
      commercial ELISA. Since production of recombinant antigen is faster and less
      expensive than production of traditional HAV antigen, the development of
      diagnostic HAV antibody tests with recombinant HAV antigen appears warranted.

PMID- 9650954
TI  - Characterization of serologically nontypeable Actinobacillus
      actinomycetemcomitans isolates.
AB  - Our previous studies have shown that Actinobacillus actinomycetemcomitans
      isolates of a given arbitrarily primed PCR (AP-PCR) genotype belong to the same
      serotype (of serotypes a through e). In the present study we investigated whether
      the AP-PCR genotypes of nonserotypeable A. actinomycetemcomitans isolates match
      those of the serotypeable isolates. The isolates were additionally characterized
      by restriction analysis of the apaH PCR amplification products. The material
      included 75 nonserotypeable and 18 serotypeable A. actinomycetemcomitans isolates
      from 34 epidemiologically unrelated subjects. The serotypeable isolates were
      obtained from subjects who also harbored nonserotypeable isolates. Eight AP-PCR
      genotypes were distinguished among the isolates; six genotypes matched those
      detected in our previous studies, whereas two genotypes were new.
      Intraindividually, the A. actinomycetemcomitans isolates produced identical AP
      PCR banding patterns, regardless of whether they were serotypeable or
      nonserotypeable, in 22 of 23 subjects participating with multiple isolates. AP
      PCR genotype 3, corresponding to serotype c, was by far the most common among the
      nonserotypeable isolates (62% of subjects). Results obtained with the apaH
      restriction analysis confirmed the results obtained with AP-PCR for 31 of the 34
      subjects. The results suggest that nonserotypeable A. actinomycetemcomitans
      isolates originate from serotypeable isolates, especially from serotype c
      isolates, and the likelihood of the existence of additional serotypes is small.

PMID- 9650955
TI  - Comparison of Roche Cobas Amplicor Mycobacterium tuberculosis assay with in-house
      PCR and culture for detection of M. tuberculosis.
AB  - The new Roche Cobas Amplicor Mycobacterium tuberculosis assay, which is a
      semiautomated version of the manually performed Roche Amplicor M. tuberculosis
      test, was compared to culture and an IS6110-based in-house PCR protocol. A total
      of 1,681 specimens from 833 patients, including specimen types other than sputum,
      were tested in parallel by both the in-house PCR and the Cobas Amplicor M.
      tuberculosis assay. After we resolved discrepant PCR results, the sensitivity,
      specificity, and positive and negative predictive values for the Cobas Amplicor
      M. tuberculosis assay were 66.33, 99.71, 94.36, and 97.66%, respectively. The
      corresponding values for the in-house PCR were 91.08, 99.85, 97.87, and 99.37%,
      respectively. For culture- and smear-positive specimens, the sensitivity of the
      Cobas Amplicor M. tuberculosis test was 96.42% (in-house PCR, 100%). If only
      smear-negative sputum specimens were considered, the Cobas Amplicor M.
      tuberculosis assay exhibited a sensitivity of 45.45% (in-house PCR, 63.63%)
      relative to that of culture. With a modified protocol for DNA extraction (washing
      of samples plus ultrasonication), both PCR methods performed better with gastric
      aspirates than with sputum samples (sensitivity of the Cobas Amplicor M.
      tuberculosis assay with smear-negative gastric aspirates, 70.00%; sensitivity of
      in-house PCR, 90.00%). With dithiothreitol being used for liquefaction of
      specimens in this study, the Cobas Amplicor M. tuberculosis assay exhibited an
      inhibition rate of 9.16%. In our view, the new Cobas Amplicor M. tuberculosis
      test (i) is well suited for typing of smear-positive specimens, (ii) may also be
      applied to gastric aspirates and other types of specimens if DNA extraction
      methods are modified appropriately, and (iii) exhibits a sensitivity with smear
      negative sputum specimens which makes it recommendable that a minimum of three
      samples from the same patient be tested.

PMID- 9650957
TI  - Identification of a granulocytic Ehrlichia strain isolated from a horse in
      Switzerland and comparison with other rickettsiae of the Ehrlichia phagocytophila
      genogroup.
AB  - This case report describes a 12-year-old Arabian mare with granulocytic
      ehrlichiosis. Clinical signs included fever, apathy, anorexia, icterus, limb
      edema, and reluctance to move. Examination of buffy coat smears revealed
      Ehrlichia organisms in neutrophils and eosinophils. A band of 1,428 bp was
      amplified from DNA of leukocytes via nested PCR and was identified as part of the
      Ehrlichia 16S rRNA gene. It differed from the gene sequences of Ehrlichia
      phagocytophila and E. equi at two and three positions, respectively.
      Interestingly, the nucleotide sequence of the 16S rRNA was 100% identical to that
      of the agent of human granulocytic ehrlichiosis.

PMID- 9650956
TI  - Rapid diagnosis of Japanese encephalitis by using an immunoglobulin M dot enzyme
      immunoassay.
AB  - Japanese encephalitis (JE) occurs in rural settings in southern and eastern Asia,
      where diagnostic facilities are limited. For the diagnosis of JE virus (JEV)
      infection, we developed a nitrocellulose membrane-based immunoglobulin M (IgM)
      capture dot enzyme immunoassay (MAC DOT) that is rapid, simple to use, requires
      no specialized equipment, and can distinguish JEV from dengue infection. In a
      prospective field study in southern Vietnam, 155 cerebrospinal fluid (CSF) and
      341 serum samples were collected from 111 children and 83 adults with suspected
      encephalitis. The JEV MAC DOT, performed on site, was scored visually from
      negative to strongly positive by two observers, and the results were compared
      subsequently with those of the standard IgM capture enzyme-linked immunosorbent
      assay. For the 179 patients with adequate specimens, the MAC DOT correctly
      identified 59 of 60 JEV-positive patients and 118 of 119 JEV-negative patients
      (sensitivity [95% confidence intervals], 98.3% [92.1 to 99.91%]; specificity,
      99.2% [95.9 to 100.0%]; positive predictive value, 0.98; negative predictive
      value, 0.99). The MAC DOT also correctly identified three patients with dengue
      encephalopathy. Admission specimens were positive for 73% of JE patients.
      Interobserver agreement for MAC DOT diagnosis was excellent (kappa = 0.94). The
      JEV MAC DOT is a simple and reliable rapid diagnostic test for JE in rural
      hospitals.

PMID- 9650958
TI  - Distribution of Staphylococcus species among human clinical specimens and emended
      description of Staphylococcus caprae.
AB  - By DNA-DNA hybridization on microplates, we identified 1,230 strains of
      staphylococci from human clinical specimens and determined the distribution of
      species. The 10 Staphylococcus species isolated most often were S. epidermidis
      (31.3%), S. aureus (23.3%), S. haemolyticus (12.2%), S. caprae (10.7%), S.
      simulans (4.4%), S. hominis (4.0%), S. capitis (3.9%), S. saprophyticus (3.6%),
      S. warneri (2.2%), and S. lugdunensis (1.3%). From these results, we realized
      that S. caprae strains were widely distributed in human clinical specimens. The
      description in Bergey's Manual of Systematic Bacteriology indicates that no
      strains of S. caprae produce acid from fructose and mannitol, but all our S.
      caprae strains produced acid from fructose and mannitol. Consequently, many
      strains of S. caprae isolated from human clinical specimens have been
      misidentified as S. haemolyticus or S. hominis by conventional biochemical tests.
      In this paper, we propose an emended description of S. caprae.

PMID- 9650959
TI  - Microtiter assay for detecting Campylobacter spp. and Helicobacter pylori with
      surface gangliosides which bind cholera toxin.
AB  - Campylobacter jejuni with Gm1 ganglioside in the core of its lipopolysaccharide
      has been associated with Guillain-Barre syndrome. Since this epitope may be of
      considerable pathophysiologic importance and since this ganglioside binds cholera
      toxin, a rapid screening assay to detect bacteria that bind cholera toxin as an
      indication of Gm1 on their surfaces was developed. In the assay, bacterial lawns
      were grown on agar plates, harvested with phosphate-buffered saline, boiled, and
      incubated with a standard concentration of cholera B subunit. Preparations from
      strains with Gm1 were observed to inhibit the binding of cholera B subunit to Gm1
      in a microtiter enzyme-linked immunosorbent assay. By using this assay with two
      groups of strains, 37 positive strains were detected among the 197 tested.
      Species with positive isolates included C. jejuni, Campylobacter coli, and
      Helicobacter pylori. The assay is capable of testing large numbers of isolates
      and should prove useful in future clinical and epidemiological studies of
      bacteria with this epitope.

PMID- 9650960
TI  - The L1 major capsid protein of human papillomavirus type 16 variants affects
      yield of virus-like particles produced in an insect cell expression system.
AB  - The L1 major capsid proteins of six human papillomavirus type 16 (HPV-16) strains
      were expressed in insect cells by using recombinant baculoviruses. Virus-like
      particles (VLPs) which appeared similar to empty virions were identified by
      electron microscopy for all HPV strains investigated. However, the yield of VLPs
      produced varied in a range from 1 to 79 depending on the HPV-16 strain. The L1
      proteins of these strains differed by up to 15 amino acids from the L1 protein of
      the prototype HPV-16 strain. Mutations in the amino acid region from residues 83
      to 97 seemed to affect the level of expression of the L1 protein. These results
      are important when considering the development of HPV vaccines and serological
      tests. They indicate that strains inducing high levels of VLP production must be
      selected for the development of vaccines. Moreover, the L1 proteins of all
      strains investigated were able to bind with DNA. We also investigated the
      seroreactivities of VLPs derived from three different HPV-16 strains from
      Algeria, Senegal, and the Philippines by testing sera from women from 11
      countries in immunoglobulin G-specific enzyme-linked immunosorbent assays. We
      observed a strong correlation between the reactivities of the three different VLP
      variants, independent of the geographical origin of the sera investigated. These
      results indicate that the three strains investigated are serologically cross
      reactive despite the fact that their L1 proteins differ in 14 amino acids and
      suggest that VLPs derived from only one HPV-16 strain could be sufficient for the
      development of an HPV-16 vaccine and anti-HPV-16 tests.

PMID- 9650961
TI  - Direct susceptibility testing with positive BacT/Alert blood cultures by using
      MicroScan overnight and rapid panels.
AB  - Studies were conducted on a method of direct inoculation of MicroScan dried
      overnight and of rapid panels with positive aerobic blood cultures obtained from
      the BacT/Alert to determine antimicrobial susceptibilities. Inocula were limited
      to specimens that appeared unimicrobic on Gram stain. Results were compared to
      those obtained from panels inoculated following subculture. For 133 gram-negative
      bacilli, there were 94.7 and 93.5% categorical agreements between direct and
      standard methods for all drugs tested with overnight and rapid panels,
      respectively. For 104 gram-positive cocci, there were 93.2 and 93.1% categorical
      agreements for overnight and rapid panels, respectively. The major error (false
      resistance) rate for gram negatives was 1.4% for overnight versus 0.7% for rapid
      panels. The very major error (false susceptibility) rate was 2.7% for overnight
      versus 8.1% for rapid panels. The total error rates were 1.6% for overnight
      panels and 1.5% for rapid panels. The major error rates for gram-positive direct
      susceptibility tests were 2.6% for overnight and 2.5% for rapid panels. The very
      major error rates were 8.8 and 7.2% for overnight and rapid panels, respectively.
      Total error rates were 3.6% for overnight and rapid gram-positive panels. These
      findings suggest that susceptibility results obtained from directly inoculated
      gram-negative overnight panels have the greatest correlation to those obtained by
      standard methods. When discrepant results occur with direct-susceptibility
      testing, they are more likely to show false susceptibility than false resistance.

PMID- 9650962
TI  - Utility of random amplified polymorphic DNA PCR and TaqMan automated detection in
      molecular identification of Aspergillus fumigatus.
AB  - We developed a method for the identification of Aspergillus fumigatus fungal
      isolates by using random amplified polymorphic DNA (RAPD) PCR (RAPD-PCR) cloning
      and the TaqMan LS50B fluorogenic detection system (Perkin-Elmer Corp., Applied
      Biosystems, Foster City, Calif.). DNA from seven clinically important Aspergillus
      species was screened by RAPD-PCR to identify section- or species-specific
      amplicons. With the OPZ19 RAPD primer a 1,264-bp product was amplified from all
      A. fumigatus strains initially examined but not from other species. A partial DNA
      sequence of this product was used to design a specific primer pair, which
      generated a single 864-bp fragment with DNA from 90 of 100 A. fumigatus isolates
      when a "touchdown" (65-->55 degrees C) annealing protocol was used. The TaqMan
      system, a fluorogenic assay which uses the 5'-->3' endonuclease activity of Taq
      DNA polymerase, detected this 864-bp product with DNA from 89 of these 90 A.
      fumigatus strains; 1 DNA sample generated an indeterminate result. With DNA from
      three morphologically typical A. fumigatus isolates, six white ("albino") A.
      fumigatus isolates, and five of six Neosartorya species (non-A. fumigatus members
      of the section Fumigati), the 864-bp product was amplified differentially at an
      annealing temperature of 56 degrees C but not with the touchdown annealing
      format. No amplicon was detected with DNA from 56 isolates of heterologous
      Aspergillus, Penicillium, and Paecilomyces species or from Neosartorya
      fennelliae; TaqMan assay results were either negative (51 isolates) or
      indeterminate (5 isolates) for all isolates. This RAPD-PCR and TaqMan assay
      offers promise as a nucleic acid-based system that can be used for the
      identification of filamentous fungal isolates and that requires no
      postamplification sample manipulations.

PMID- 9650963
TI  - Q fever in the Greek island of Crete: detection, isolation, and molecular
      identification of eight strains of Coxiella burnetii from clinical samples.
AB  - Over a period of 6 years (1989 to 1995), serum samples from 3,300 patients
      suspected to be infected by Coxiella burnetii were assayed for the presence of
      antibodies against antigen phase II of the microorganism by the indirect
      immunofluorescence antibody technique (IFAT). One hundred fifty-two cases were
      recorded, and blood samples from 17 patients were cultured for the isolation of
      the pathogen. By a centrifugation shell vial technique, eight strains were
      isolated from patients suffering from acute Q fever. The microorganism was
      detected in the cultures by IFAT, by Gimenez staining, and by the cytopathogenic
      effect on Vero and human embryonic lung (HEL) cells. PCR followed by restriction
      fragment length polymorphism analysis was used to confirm the diagnosis and
      identify the Coxiella burnetii strains within the cell cultures as well as to
      compare them with reference strains. In order to avoid time-consuming cultures,
      to achieve direct detection of Coxiella burnetii in clinical samples (blood,
      buffy coat, etc.), and to increase the specificity and sensitivity of the
      detection, nested PCR was performed. The first step of DNA extraction was
      performed with the QIAamp blood kit 250. For the second step of the PCR assays,
      the conditions of temperature and times of recycling were properly modified, and
      the microorganism was detected within 4 h. Our study demonstrates that Q fever is
      an endemic disease in Crete and that the diagnosis of Coxiella burnetii infection
      can be rapidly achieved by the detection of the microorganism in buffy coat
      samples by nested PCR. Although the presenting symptoms of the disease in this
      study differed from those in other studies, the Cretan strains do not differ
      genotypically from the reference strains (Nine Mile and Q212).

PMID- 9650964
TI  - Diagnostic use of PCR for detection of Pneumocystis carinii in oral wash samples.
AB  - There is a need to develop noninvasive methods for the diagnosis of Pneumocystis
      carinii pneumonia in patients unable to undergo bronchoscopy or induction sputum.
      Oral wash specimens are easily obtained, and P. carinii nucleic acid can be
      amplified and demonstrated by PCR. In routine clinical use, easy sample
      processing and single-round PCR are needed to ensure rapid analysis and to reduce
      the risk of contamination. We developed a single-round Touchdown PCR (TD-PCR)
      protocol with the ability to detect PCR inhibition in the specimen. The TD-PCR
      was evaluated in a routine diagnostic laboratory and was compared to a previously
      described PCR protocol (mitochondrial RNA) run in a research laboratory. Both PCR
      methods amplified a sequence of the mitochondrial rRNA gene of P. carinii. Paired
      bronchoalveolar lavage (BAL) and oral wash specimens from 76 consecutive human
      immunodeficiency virus type 1-infected persons undergoing a diagnostic
      bronchoscopy were included. The TD-PCR procedure was quicker than the
      mitochondrial PCR procedure (<24 versus 48 h) and, compared to microscopy, had
      sensitivity, specificity, and positive and negative predictive values of 89, 94,
      93, and 91%, respectively, for oral wash specimens and 100, 91, 90, and 100%,
      respectively, for BAL specimens. Our results suggest that oral wash specimens are
      a potential noninvasive method to obtain a diagnostic specimen during P. carinii
      pneumonia infection and that it can be applied in a routine diagnostic
      laboratory.

PMID- 9650965
TI  - Assessment of spontaneous fluctuations of viral load in untreated patients with
      chronic hepatitis C by two standardized quantitation methods: branched DNA and
      Amplicor Monitor.
AB  - Quantitation of hepatitis C virus (HCV) RNA in serum has been used to predict and
      monitor the efficacy of interferon therapy in chronic HCV infection. We
      prospectively studied the fluctuation of viremia by a longitudinal follow-up of
      HCV RNA levels for 2 months in six untreated patients. Spontaneous fluctuations
      of HCV RNA ranged from 2.8- to 5.7-fold with branched DNA assay and from 2.9- to
      5.6-fold with Monitor. These large spontaneous fluctuations (up to 0.75 log),
      observed daily, weekly, and monthly, raise doubt about the clinical value of a
      single assessment of pretherapeutic viremia.

PMID- 9650966
TI  - Survey of incidence of Clostridium difficile infection in Canadian hospitals and
      diagnostic approaches.
AB  - A questionnaire relating to Clostridium difficile disease incidence and
      diagnostic practices was sent to 380 Canadian hospitals (all with > 50 beds). The
      national questionnaire response rate was 63%. In-house testing was performed in
      17.6, 61.5, and 74.2% of the hospitals with < 300, 300 to 500, and > 500 beds,
      respectively. The average test positivity rates were 17.2, 15.3, and 13.2% for
      hospitals with < 300, 300 to 500, and > 500 beds, respectively. The average
      disease incidences were 23.5, 30.8, and 40.3 cases per 100,000 patient days in
      the hospitals with < 300, 300 to 500, and > 500 beds, respectively. In the 81
      hospitals where in-house testing was performed, cytotoxin testing utilizing
      tissue culture was most common (44.4%), followed by enzyme-linked immunosorbent
      assay (38.3%), culture for toxigenic C. difficile (32.1%), and latex
      agglutination (13.6%). The clinical criteria for C. difficile testing were
      variable, with 85% of hospitals indicating that a test was done automatically if
      ordered by a doctor. Our results show that C. difficile-associated diarrhea is a
      major problem in hospitals with > or = 200 beds. Despite a lower disease
      incidence in smaller hospitals, there was a higher diagnostic test positivity
      rate. This may reflect the preference of smaller hospitals for culture and latex
      agglutination tests.

PMID- 9650967
TI  - Molecular diagnosis of human rhinovirus infections: comparison with virus
      isolation.
AB  - To compare the sensitivity and specificity of RT-PCR with that of virus isolation
      in the detection of human rhinoviruses, we tested nasopharyngeal aspirates from
      200 patients on the 1st and 7th days after the onset of the common cold. An assay
      utilizing a short amplicon in the conserved 5' noncoding region was found highly
      sensitive. Of 192 positive samples altogether, 65 were found positive by RT-PCR
      only, 6 were positive by isolation exclusively, and 121 gave positive results in
      both tests.

PMID- 9650968
TI  - Low-level viremia and intracellular expression of hepatitis B surface antigen
      (HBsAg) in HBsAg carriers with concurrent hepatitis C virus infection.
AB  - Assays of hepatitis B virus (HBV) replication and antigen expression in HBV
      surface antigen (HBsAg) carriers with concurrent hepatitis C or D virus (HCV or
      HDV) infection revealed that HCV and HDV can suppress HBV replication but that
      HCV also substantially suppresses HBV surface protein expression. HBsAg carriers
      with concurrent HCV infection thus have low-level viremia and intracellular
      HBsAg.

PMID- 9650969
TI  - Coryneform bacteria in throat cultures of healthy individuals.
AB  - Throat swabs from 113 healthy individuals from Hamburg, Germany, and Zurich,
      Switzerland, were investigated for coryneform bacteria with nonselective and
      selective media. Ninety specimens contained 123 strains. Surprisingly, 76% of
      them were strains of Corynebacterium durum (47%) and Rothia dentocariosa (29%).
      Only two were strains of Corynebacterium pseudodiphtheriticum, and none were
      strains of C. striatum, C. amycolatum, or C. diphtheriae.

PMID- 9650970
TI  - Clinical importance of identifying coagulase-negative staphylococci isolated from
      blood cultures: evaluation of MicroScan Rapid and Dried Overnight Gram-Positive
      panels versus a conventional reference method.
AB  - We evaluated the clinical usefulness of species identification of blood isolates
      of coagulase-negative staphylococci as a predictor of the clinical significance
      of the isolates. In addition, we compared results of species identification
      obtained with MicroScan Rapid Gram-Positive Identification panels and Dried
      Overnight (Conventional) Gram-Positive Identification panels with those obtained
      by a tube reference method. Two hundred eighty-five blood isolates were tested,
      including 92 judged to represent true bacteremia and 193 judged to represent
      contamination. The most common species detected were Staphylococcus epidermidis,
      Staphylococcus hominis, and Staphylococcus haemolyticus. These three species
      accounted for nearly 98% of the clinically significant isolates and 89% of the
      contaminants. The isolation of other species almost always represented
      contamination. However, identification of the three most common species did not
      help distinguish pathogens from contaminants. Both the Rapid and the Dried
      Overnight Gram-Positive panels identified S. epidermidis strains accurately, but
      the panels performed less well for the other species. Analysis revealed that S.
      hominis was frequently misidentified due to the presence of a previously unknown
      subspecies. Based on the initial results, revised investigational Dried Overnight
      Gram-Positive Identification panels (CPID-2) were prepared and tested. The CPID-2
      panels identified 85 to 95% of S. epidermidis strains, 76 to 86% of S. hominis
      strains, and 88 to 92% of S. haemolyticus strains with high probability (>85%)
      and, overall, represented a significant improvement over the other panels for
      identification of these staphylococcal species.

PMID- 9650971
TI  - Simple, inexpensive, reliable method for differentiation of Candida dubliniensis
      from Candida albicans.
AB  - Candida dubliniensis is a recently described pathogenic species which shares many
      phenotypic features with Candida albicans, including the ability to form germ
      tubes and chlamydospores. These similarities have caused significant problems in
      the identification of C. dubliniensis by the average clinical mycology
      laboratory. To facilitate the differentiation of these species, we investigated
      the growth of 120 isolates of C. dubliniensis and 98 C. albicans isolates at 42
      and 45 degrees C on Emmons' modified Sabouraud glucose agar (SGA) and 10 isolates
      of each species in yeast-peptone-dextrose broth. None of the C. dubliniensis
      isolates grew on the agar or in the broth medium at 45 degrees C, while 11
      isolates were capable of growing on SGA at 42 degrees C. In contrast, all of the
      C. albicans isolates but one grew at 45 degrees C on or in either medium. These
      reproducible results clearly demonstrate that the incubation of isolates
      suspected to be C. dubliniensis or C. albicans at 45 degrees C provides a simple,
      reliable, and inexpensive method for the differentiation of the two species.

PMID- 9650972
TI  - Quantification of human immunodeficiency virus type 1 RNA levels in plasma by
      using small-volume-format branched-DNA assays.
AB  - We have developed small-volume (50 or 250 microl)-format branched-DNA assays for
      human immunodeficiency virus type 1 (HIV-1) RNA for use with specimens in which
      the volume is limited and/or a high viral load is anticipated. These formats
      exhibited good correlation with the standard 1-ml format; high specificity,
      reproducibility, and linearity; and no significant difference in the
      quantification of HIV-1 subtypes.

PMID- 9650973
TI  - Clonal nature of enterotoxigenic Escherichia coli serotype O6:H16 revealed by
      randomly amplified polymorphic DNA analysis.
AB  - The genetic relatedness among 29 enterotoxigenic Escherichia coli strains of
      serotype O6:H16 was investigated by randomly amplified polymorphic DNA (RAPD)
      analysis. The strains were isolated in different parts of the world, displayed
      CS1-CS3 or CS2-CS3 profiles, and expressed heat-labile toxin (LT) and heat-stable
      toxin; a single strain expressed only LT. Ten RAPD types were distinguished and
      showed significant similarity, having on average 82% of the amplified bands in
      common. These results indicated that, irrespective of the different geographical
      origin or virulence factors, these strains belonged to a widespread clonal group.

PMID- 9650974
TI  - Evidence of Toscana virus variants circulating in Tuscany, Italy, during the
      summers of 1995 to 1997.
AB  - The Toscana virus can cause neurological infection in adults. This study of 112
      cases of acute meningitis which occurred during the summers of 1995, 1996, and
      1997 demonstrated the presence of viral RNA in the cerebrospinal fluid of 56
      patients. Their sequence analysis shows four variants of the Toscana virus.

PMID- 9650975
TI  - Genetic analysis of multiple vancomycin-resistant Enterococcus isolates obtained
      serially from two long-term-care patients.
AB  - Fifty-eight vancomycin-resistant enterococcal isolates were obtained from two
      patients over 9 weeks. Numerous pulsed-field gel electrophoresis fingerprinting
      types were isolated from each patient. By PCR, all isolates were vanA+. However,
      many isolates from patient B were found to lack vanA by hybridization. Our
      results demonstrate the importance of examining multiple isolates, especially
      from patients who are at high risk of infection.

PMID- 9650976
TI  - Replication of bovine herpesvirus type 4 in human cells in vitro.
AB  - A reference strain (Movar 33/63) of bovine herpesvirus type 4 (BHV-4) was
      inoculated into 14 different human cell lines and five primary cell cultures
      representing various human tissues. BHV-4 replicated in two embryonic lung cell
      lines, MRC-5 and Wistar-38, and in a giant-cell glioblastoma cell culture.
      Cytopathic effect and intranuclear inclusion bodies were observed in these cells.
      PCR detected a 10,000-times-higher level of BHV-4 DNA. Titration of the
      supernatant indicated a 100-fold increase of infectious particles. Since this is
      the first bovine (human herpesvirus 8 and Epstein-Barr virus related) herpesvirus
      which replicates on human cells in vitro, the danger of possible human BHV-4
      infection should not be ignored.

PMID- 9650977
TI  - Use of fluorescent-antibody staining of cytocentrifuge-prepared smears in
      combination with cell culture for direct detection of respiratory viruses.
AB  - Over a 3-year period, 1,003 respiratory samples were collected and examined for
      selected respiratory viruses with cytocentrifuged prepared smears stained with
      fluorescently labeled antibodies (IFA) in conjunction with cell culture. IFA
      results were compared with results obtained by cell culture. Viruses were
      isolated or detected by direct means in 401 samples. Agreement between culture
      and IFA was 90%.

PMID- 9650978
TI  - Sudden increase in isolation of group B streptococci, serotype V, is not due to
      emergence of a new pulsed-field gel electrophoresis type.
AB  - Until recently, group B streptococcus, serotype V (GBS-V), was an infrequent
      cause of disease. It is now recognized as a significant cause of infections in
      both children and adults. To determine if this increase was due to the recent
      introduction and spread of a single clone of GBS-V, we analyzed, by pulsed-field
      gel electrophoresis (PFGE), the SmaI chromosomal DNA digests of 45 bacteria: 41
      isolated from human infections between 1986 and 1996 in the United States, 2 from
      human infections in Argentina, and 2 from naturally infected mice. Seventeen
      patterns were found and arbitrarily designated patterns A to Q. Pattern N
      constituted 24 (53%) of the isolates and was found in all of the years tested and
      from all surveillance areas, as well as in both isolates from Argentina, and was
      very similar to the GBS-V isolated from a mouse. Pattern P was found in three
      isolates, pattern F was found in two, and the remaining patterns were found in
      one isolate each. We concluded that the majority of isolates of GBS-V are of one
      PFGE subtype and that this subtype was predominate before the increase in disease
      caused by GBS-V and that GBS-V disease is caused by several different subtypes.

PMID- 9650979
TI  - Effects of various handling and storage conditions on stability of Treponema
      pallidum DNA in cerebrospinal fluid.
AB  - Treponema pallidum DNA from even small numbers of organisms was detectable in
      cerebrospinal fluid (CSF) stored at room temperature or at 4 degrees C for
      several hours and in CSF subjected to three freeze-thaw cycles. These results
      suggest that negative PCR results for T. pallidum from patients diagnosed with T.
      pallidum invasion of the central nervous system are probably not due to the loss
      of target DNA prior to testing.

PMID- 9650980
TI  - Comparison of sample preparation methods for detection of Legionella pneumophila
      in culture-positive bronchoalveolar lavage fluids by PCR.
AB  - A prospective study was conducted on 25 Legionella pneumophila culture-positive
      and 98 culture-negative bronchoalveolar lavage fluid samples to compare two DNA
      preparation methods: a rapid modified Chelex-based protocol and a proteinase K
      method. PCR was found to be more sensitive with the Chelex-based method (P =
      0.03). N difference was found concerning the inhibition rate.

PMID- 9650981
TI  - Chromosomal rearrangements in Salmonella enterica serotype typhi affecting
      molecular typing in outbreak investigations.
AB  - Salmonella enterica serotype Typhi strains belonging to eight different outbreaks
      of typhoid fever that occurred in Spain between 1989 and 1994 were analyzed by
      ribotyping and pulsed-field gel electrophoresis. For three outbreaks, two
      different patterns were detected for each outbreak. The partial digestion
      analysis by the intron-encoded endonuclease I-CeuI of the two different strains
      from each outbreak provided an excellent tool for examining the organization of
      the genomes of epidemiologically related strains. S. enterica serotype Typhi
      seems to be more susceptible than other serotypes to genetic rearrangements
      produced by homologous recombinations between rrn operons; these rearrangements
      do not substantially alter the stability or survival of the bacterium. We
      conclude that genetic rearrangements can occur during the emergence of an
      outbreak.

PMID- 9650982
TI  - Borna disease in a dog with lethal meningoencephalitis.
AB  - A dog was euthanatized because of progressive neurological signs. Histologically,
      a nonsuppurative meningoencephalitis was found. By immunohistochemistry, in situ
      hybridization, and nested PCR procedures, Borna disease virus (BDV) antigen and
      BDV-specific RNA were demonstrated in brain tissues of the dog. The nucleotide
      sequence of the PCR product showed 94 to 98% homology to published BDV sequences.
      This is the first description of Borna disease in a dog.

PMID- 9650983
TI  - Experimental transmission of Ehrlichia equi to horses through naturally infected
      ticks (Ixodes pacificus) from Northern California.
AB  - We report the experimental transmission of Ehrlichia equi from naturally infected
      Ixodes pacificus ticks to horses. Three weeks after exposure to ticks, two of
      three horses developed clinical signs compatible with E. equi infection, while
      one horse remained asymptomatic. 16S rRNA gene PCR of blood leukocyte lysates was
      positive for all horses at various time points; two horses seroconverted. The 16S
      rRNA gene sequences amplified from tick-exposed horses showed more than 99%
      homology to corresponding fragments of the 16S rRNA genes of E. equi, Ehrlichia
      phagocytophila, and the human granulocytic ehrlichiosis agent.

PMID- 9650984
TI  - Isolation and characterization of sorbitol-fermenting Shiga toxin (Verocytotoxin)
      producing Escherichia coli O157:H- strains in the Czech Republic.
AB  - Two sorbitol-fermenting (SF) Shiga toxin-producing Escherichia coli (STEC) O157:H
      strains were isolated from patients with hemolytic-uremic syndrome in the Czech
      Republic in 1995. Their phenotypic and genotypic characteristics and genomic DNA
      fingerprints were identical or closely related to those of SF STEC O157:H-
      strains isolated in Germany in 1988 to 1997. This indicates that the Czech
      isolates belong to the SF STEC O157 clone which is widespread in Germany. It is
      the first finding of the clone outside Germany.

PMID- 9650985
TI  - Bacillus thuringiensis subsp. konkukian (serotype H34) superinfection: case
      report and experimental evidence of pathogenicity in immunosuppressed mice.
AB  - We present a case of severe war wounds infected by Bacillus thuringiensis
      serotype H34 and describe the experimental protocol used to demonstrate its
      ability to infect mice after cutaneous inoculation. This case is interesting
      because B. thuringiensis is considered to be a contaminant in laboratories and
      receives inadequate attention.

PMID- 9650986
TI  - Therapeutic effect of doxycycline in experimental subclinical canine monocytic
      ehrlichiosis: evaluation of a 6-week course.
AB  - The efficacy of doxycycline treatment (10 mg/kg of body weight every 24 h for 42
      days) in eliminating Ehrlichia canis from four subclinically infected dogs was
      evaluated. One dog remained PCR positive, suggesting that 6 weeks of doxycycline
      treatment may not be sufficient to clear E. canis parasites from all
      subclinically infected dogs. Serology (indirect immunofluorescent antibody assay)
      was shown to be unreliable in assessing recovery from the carrier state, as anti
      E. canis antibodies persisted after elimination of the parasite. Our findings
      suggest that an increase in the platelet count may be an important indicator for
      dogs that recover from subclinical ehrlichiosis.

PMID- 9650987
TI  - Line probe assay for detection of human immunodeficiency virus type 1 mutations
      conferring resistance to nucleoside inhibitors of reverse transcriptase:
      comparison with sequence analysis.
AB  - We compared the line probe assay (LiPA) to sequence analysis for the detection of
      mutations conferring resistance to nucleoside inhibitors of human
      immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). Plasma samples
      from 40 patients who had received zidovudine, dideoxyinosine, and
      dideoxycytosine, alone or in combination, and who were enrolled in the ALTIS 2
      clinical trial (lamivudine [3TC] plus stavudine) were tested at enrollment and at
      week 24. RT PCR products from plasma were used for LiPA, and DNA was used for
      sequence analysis. LiPA gave uninterpretable results for 8.5% of the analyzed
      codons corresponding to 63 samples, mainly for codons 41, 69, and 70. Several
      minor discrepancies between the two methods occurred, mainly due to the ability
      of LiPA to detect mixed populations while sequence analyses detect a single
      homogeneous population. LiPA is suitable for detecting mixed populations and easy
      to implement in clinical laboratories and might be useful for epidemiological
      surveys of primary HIV-1 resistance.

PMID- 9650988
TI  - Facklamia ignava sp. nov., isolated from human clinical specimens.
AB  - Two strains of a hitherto-undescribed gram-positive, catalase-negative coccus
      isolated from human sources were characterized by phenotypic and molecular
      taxonomic methods. Comparative 16S rRNA gene sequencing studies demonstrated that
      the unknown strains are genealogically identical and constitute a new line close
      to, but distinct from, Facklamia hominis. The unknown bacterium was readily
      distinguished from F. hominis by biochemical tests and electrophoretic analysis
      of whole-cell proteins. On the basis of phylogenetic and phenotypic evidence, it
      is proposed that the unknown bacterium be classified as Facklamia ignava sp. nov.
      The type strain of Facklamia ignava is CCUG 37419.

PMID- 9650989
TI  - Molecular epidemiology of reemergent Vibrio cholerae O139 Bengal in India.
AB  - We report the prevalence of the O139 serogroup in Calcutta, India, after its
      reemergence in August 1996 and the spread of the reemerged clone to other parts
      of the country by using previously established molecular markers. Phenotypically,
      the reemerged Vibrio cholerae O139 displayed a difference compared to those that
      appeared in late 1992 and 1993 in that the current O139 strains are sensitive to
      co-trimoxazole. Ribotyping with the enzyme BglI produced two rRNA restriction
      patterns in the O139 strains isolated after August 1996, and these patterns were
      identical to those exhibited by strains of O139 isolated in 1992. Three clones of
      V. cholerae O139 are currently prevailing in the country, with strains exhibiting
      three bands after HindIII digestion and hybridization with a ctxA probe being
      dominant. The reemergence of V. cholerae O139 in Calcutta after a 32-month
      quiescent period reestablishes the O139 serogroup as an entity which is likely to
      play a crucial role in the temporal antigenic variations among the serogroups of
      V. cholerae causing cholera.

PMID- 9650990
TI  - Differentiation of Rhizomucor species by carbon source utilization and isoenzyme
      analysis.
AB  - Nineteen Rhizomucor miehei and Rhizomucor pusillus isolates were assayed for
      their ability to utilize 87 various substrates as a single carbon source. Besides
      a difference in sucrose utilization, distinctive differences were found in the
      utilization of glycine, phenylalanine, and beta-alanine. Five isoenzyme systems
      also proved useful for the determination of markers of distinctive value at a
      species level. Data were used to obtain information about the genetic
      polymorphism of these species: a high degree of variability was found among the
      R. pusillus isolates, whereas the group of R. miehei isolates was more
      homogeneous genetically.

PMID- 9650992
TI  - Streptococcus iniae, a human and animal pathogen: specific identification by the
      chaperonin 60 gene identification method.
AB  - It was recently reported that Streptococcus iniae, a bacterial pathogen of
      aquatic animals, can cause serious disease in humans. Using the chaperonin 60
      (Cpn60) gene identification method with reverse checkerboard hybridization and
      chemiluminescent detection, we identified correctly each of 12 S. iniae samples
      among 34 aerobic gram-positive isolates from animal and clinical human sources.

PMID- 9650991
TI  - Fatal Hormonema dematioides peritonitis in a patient on continuous ambulatory
      peritoneal dialysis: criteria for organism identification and review of other
      known fungal etiologic agents.
AB  - We report a fatal case a fungal peritonitis caused by the yeast-like dematiaceous
      mould Hormonema dematioides in a 45-year-old woman. The woman had a 13-year
      history of insulin-dependent diabetes mellitus and had been on continuous
      ambulatory peritoneal dialysis for chronic renal failure. H. dematioides was
      repeatedly isolated from the dialysate culture specimens collected on days 3, 9,
      16, and 20 of her hospital stay. Preliminary culture reports on day 7 of the
      growth of a yeast-like fungus, a probable Candida species, prompted the
      administration of fluconazole (FLU). Intraperitoneal and intravenous FLU failed
      to eliminate the mould, and the patient expired on day 21 of her hospital stay.
      We use this case to present what appears to be the first report of fungal
      peritonitis due to H. dematioides, to provide laboratorians with criteria for
      differentiating this organism from the similar mould Aureobasidium pullulans and
      from various yeast genera, and to provide a review of known fungal taxa inciting
      peritonitis.

PMID- 9650993
TI  - Molecular cloning and DNA sequencing of the Staphylococcus aureus UDP-N
      acetylmuramyl tripeptide synthetase (murE) gene, essential for the optimal
      expression of methicillin resistance.
AB  - The Tn551 insertion in mutant RUSA235 of a highly methicillin resistant
      Staphylococcus aureus strain results in drastic reduction in the level of
      methicillin resistance and abnormalities, both in the composition of the
      peptidoglycan and of the cell wall precursor pool. Cloning and sequencing of the
      inactivated gene indicates that it is the murE gene of Staphylococcus aureus.

PMID- 9650994
TI  - Characterization of a mutationally altered dihydropteroate synthase contributing
      to sulfathiazole resistance in Escherichia coli.
AB  - A series of Escherichia coli strains were selected for increasing resistance to
      sulfathiazole. Resistance occurred in seven increments, suggesting the
      accumulation of several mutations that contributed to overall sulfathiazole
      resistance. All of the resistant strains had a sulfathiazole-resistant
      dihydropteroate synthase with a Pro to Ser substitution at amino acid position
      64. Overproduction of the wild-type enzyme did not result in sulfathiazole
      resistance, however overproduction of the mutant enzyme resulted in significant
      resistance. Conversely, overproduction of the wild-type enzyme in a sulfathiazole
      resistant background resulted in a decrease in resistance. Although the specific
      activity of DHPS in crude extracts was not significantly different from the wild
      type, the amino acid substitution resulted in an enzyme with a tenfold increase
      in the Km for p-aminobenzoate, and a 100-fold increase in the Ki for
      sulfathiazole.

PMID- 9650995
TI  - Limiting the spread of penicillin-resistant Streptococcus pneumoniae: experiences
      from the South Swedish Pneumococcal Intervention Project.
AB  - In an attempt to limit the spread of penicillin-resistant pneumococci (PRP), an
      intervention project was initiated in the Malmohus County, southern Sweden in
      January 1995. The ongoing project combines traditional communicable disease
      control measures and actions aiming at reducing antibiotics consumption. All
      patients in the county with a nasopharyngeal culture positive for PRP with MIC of
      Penicillin G > or =0.5 mg/L are followed with nasopharyngeal cultures until PRP
      negative. Nasopharyngeal cultures are obtained from family members and close
      contacts of the index cases. Preschool children carrying PRP are denied
      attendance at group day-care. From January 1995 to March 1997, 1,038 PRP-carriers
      (429 index cases and 609 contact cases) were identified. Children aged 1-6 years
      dominated (83%). Antibiotics sales decreased during the study period, and
      epidemiologic data indicate that the intervention may have limited the
      dissemination of PRP in the county, but further evaluation is needed.

PMID- 9650996
TI  - Spread of the multiresistant Iberian clone of methicillin-resistant
      Staphylococcus aureus (MRSA) to Italy and Scotland.
AB  - The multidrug-resistant "Iberian" clone of methicillin-resistant Staphylococcus
      aureus (MRSA) was first identified on the basis of its unique DNA fingerprints as
      the strain responsible for the massive 1989 outbreak of MRSA disease in the
      hospital Princeps d'Espanya, Barcelona, Spain. Most Iberian MRSA carry a
      constitutive beta-lactamase. They are resistant to most beta-lactam antibiotics,
      macrolides, aminoglycosides, tetracycline, rifampin and ciprofloxacin and are
      susceptible to fosfomycin, fusidic acid, mupirocin, sulfamethoxazole/trimethoprim
      and vancomycin. The characteristic DNA fingerprints of the clone include the mecA
      polymorph I, Tn554 pattern E (or its variants), a chromosomal macrorestriction
      pattern (pulsed-field gel electrophoretic type) A (or its subtype variants), the
      lack of the mecI regulatory gene and a homogeneous, high level of expression of
      methicillin resistance. Molecular surveillance studies have documented the
      extensive spread of this clone to many Portuguese hospitals during the 1990s. In
      this article, we describe the spread of the Iberian MRSA to hospitals in Rome,
      Italy, and Scotland.

PMID- 9650997
TI  - Molecular epidemiology of antibiotic resistance genes in multiresistant epidemic
      Salmonella typhimurium DT 104.
AB  - The epidemiology of antibiotic resistance genes in epidemic multiresistant S.
      typhimurium DT 104 of human and animal origin was investigated. DNA prepared from
      45 human and 21 animal strains isolated between 1984 and 1997, including eight
      isolated in other European countries, the USA, Trinidad, and South Africa and
      resistant to ampicillin, chloramphenicol, streptomycin, sulphonamides,
      spectinomycin, tetracyclines (R-type ACSSuSpT) were examined for the presence of
      integrons by PCR. Integron hot spots were observed in all strains conferring
      resistance to ACSSuSpT in two copies, determined by two discrete bands of
      approximately 1.0 and 1.2 kb. Direct nucleotide sequencing of the individual
      amplicons of selected strains indicated that the 1.0 kb gene product was ant (3")
      Ia, responsible for resistance to streptomycin and spectinomycin; the 1.2 kb
      amplicon contained the gene blaPSE-1, encoding the beta-lactamase PSE-1 (CARB-2).
      Both integrons were encoded on a single XbaI macrorestriction fragment of
      approximately 10 kb. All isolates of DT 104 of this resistance phenotype
      contained the same inserted gene cassettes, irrespective of source and country of
      origin, supporting the suggestion of the spread of an epidemic clone. Sequence
      analysis of the quinolone resistance determining region (QRDR) of gyrA of 15
      multiresistant strains conferring additional resistance to nalidixic acid and
      ciprofloxacin (R-type ACSSuSpTNxCp) identified two discrete base substitutions at
      codon Asp-87. Conversion of Asp-87 --> Asn was most commonly observed, in 7/10
      human and 4/5 animal isolates, suggesting that this codon plays a major role in
      the development of ciprofloxacin resistance in multiresistant S. typhimurium DT
      104.

PMID- 9650998
TI  - Trends in antibiotic resistance of staphylococci over an eight-year period:
      differences in the emergence of resistance between coagulase positive and
      coagulase-negative staphylococci.
AB  - The antimicrobial susceptibilities of 1058 Staphylococcus aureus and 2,163
      coagulase-negative staphylococci (CNS) isolates obtained from clinical specimen
      between 1988 and 1995, were determined against 13 anti-staphylococcal
      antibiotics. During the study period the resistance of Staphylococcus aureus to
      ciprofloxacin, ceftazidime, and norfloxacin increased significantly by 7%, 4%,
      and 6%, respectively (p < or = 0.001). By comparison, the antibiotic resistance
      of CNS to ceftazidime, oxacillin, norfloxacin, ciprofloxacin, fusidic acid, and
      cefoxitin increased by 20%, 17%, 15%, 14%, 12% and 10%, respectively (p < or =
      0.001). Invasive and noninvasive S. aureus had similar antibiotic resistance,
      whereas CNS invasive isolates were more resistant than noninvasive isolates to
      every antibiotics, except vancomycin and fusidic acid. These differences were
      significant (p < 0.001) for oxacillin, cefoxitin, and clindamycin. Our
      observations confirm that staphylococci and particularly CNS isolates show an
      important rate of increased resistance to the standard antimicrobials used for
      therapy, and that the rate of emergence of resistance differ considerably between
      coagulase-positive and coagulase-negative staphylococci.

PMID- 9650999
TI  - Antimicrobial susceptibility profiles of oropharyngeal viridans group
      streptococci isolates from cystic fibrosis and non-cystic fibrosis patients.
AB  - The antimicrobial susceptibility profile of 77 oropharyngeal viridans
      streptococci isolates from 34 cystic fibrosis (CF) patients and 58 isolates from
      43 healthy non-CF patients were studied by the E-test and the standard disk
      diffusion methods. Overall penicillin and cefotaxime resistances (intermediate
      plus resistant isolates) were significantly higher (p < 0.05) among CF isolates
      (72.7% and 45.5%, respectively) than among non-CF isolates (51.7% and 15.5%,
      respectively). No significant difference was observed in overall (intermediate
      plus resistant) erythromycin resistance rates, although high-level erythromycin
      resistance (> or =32 microg/mL) was more frequently found in CF isolates (24.6%)
      than in non-CF isolates (12.1%). An unexpected high percentage of isolates showed
      low level erythromycin resistance (MIC range, 0.5-15 microg/mL): 41.5% in cystic
      fibrosis and 46.5% in non-CF isolates. No significant differences were observed
      regarding the percentage of colonized patients with at least one penicillin
      resistant isolate. On the contrary, colonization with cefotaxime (p < 0.001) or
      erythromycin (p = 0.014) resistant isolates were significantly more prevalent in
      CF patients. Similar tetracycline and chloramphenicol resistance rates were
      observed for both groups. Viridans isolates resistant to a single antibiotic were
      more prevalent among non-CF patients and multiple resistance was higher among CF
      patients. Prior antibiotic exposure could result in differences in beta-lactam
      resistance and colonization rates with resistant isolates between both groups.
      None of the non-CF patients was previously treated with antimicrobials for a
      period of three months before sampling. In contrast, 94.1% of CF patients were
      treated with antimicrobials within the same period; 65.6% with beta-lactam
      antibiotics. Patients with CF disease, frequently exposed to antimicrobials, may
      be a reservoir of viridans streptococci isolates with resistance determinants,
      particularly to beta-lactam antibiotics.

PMID- 9651000
TI  - Phase variation in colony opacity by Streptococcus pneumoniae.

PMID- 9651001
TI  - Association between decreased susceptibility to a new antibiotic for treatment of
      human diseases, everninomicin (SCH 27899), and resistance to an antibiotic used
      for growth promotion in animals, avilamycin.
AB  - The emergence of multiresistant bacteria has increased the need for new
      antibiotics or modifications of older antibiotics. One promising agent might be
      the everninomicin SCH 27899, an oligosaccharide antibiotic recently developed by
      Schering Plough. However, another oligosaccharide, avilamycin, that is
      structurally very similar has been used as a growth promoter for food animals in
      the EU for several years, and a very frequent occurrence of resistance to
      avilamycin has been found among Enterococcus faecium isolates from broilers in
      Denmark. This study was conducted to investigate whether the resistance to
      avilamycin was associated with decreased susceptibility to everninomicin. From
      broilers, a total of 31 avilamycin susceptible and 55 avilamycin resistant (MIC
      >16 microg/mL) E. faecium isolates were selected. From pigs, 21 avilamycin
      susceptible and eight avilamycin-resistant Enterococcus faecalis and 50
      avilamycin-susceptible and two avilamycin-resistant E. faecium isolates were
      selected. All isolates were tested for susceptibility to everninomicin by E-test.
      The avilamycin-susceptible enterococci isolates had MICs to everninomicin from
      0.064 to 0.75 microg/mL (MIC50 = 0.38 microg/mL) and the avilamycin-resistant
      isolates had MICs from 1.5 to 16 microg/mL (MIC50 = 3 microg/mL). Complete
      agreement between decreased susceptibility to avilamycin and everninomicin was
      found. This study showed that the use of avilamycin as a growth promoter for
      broilers and pigs has created a reservoir of E. faecium and E. faecalis isolates
      with decreased susceptibility to everninomicin among food animals already before
      this antibiotic have been finally developed for human use.

PMID- 9651002
TI  - Early formation of sexually dimorphic glomeruli in the developing olfactory lobe
      of the brain of the moth Manduca sexta.
AB  - The antennal lobes (ALs), the primary olfactory centers, of the moth Manduca
      sexta are sexually dimorphic. Only ALs of males possess the macroglomerular
      complex (MGC), the site of primary processing of information about the female's
      sex pheromone. To understand the development of identified, odor-specific
      olfactory glomeruli, we investigated the cellular events involved in the
      morphogenesis of the MGC by means of various fluorescence staining techniques and
      laser-scanning confocal microscopy. The MGC lies near the entrance of the
      antennal nerve into the AL of the adult male and comprises three glomeruli, the
      globular cumulus and two toroidal structures. The MGC forms during early stages
      of metamorphic adult development through a stereotyped sequence of coordinated
      changes in MGC-specific receptor axons, glial cells, and early-ingrowing
      projection neurons of the medial group of AL neurons. The MGC divisions are the
      earliest glomeruli to form in the male AL, and their basic organization is
      established within about 3 days after ingrowth of the first sensory axons.
      Despite their special anatomical features, the MGC glomeruli develop in a manner
      similar to that of the ordinary glomeruli. Comparison of the ALs of males and
      females reveals that two relatively large and early-developing glomeruli that are
      situated dorsolaterally in the female AL appear to be female-specific.
      Development of the sexually dimorphic glomeruli diverges immediately after the
      ingrowth of the first olfactory receptor axons, resulting in the formation of
      these large glomeruli in females and the MGC in males.

PMID- 9651003
TI  - Characterisation of the adventitial rectal ganglia in the male rat by their
      immunohistochemical features and projections.
AB  - In recent years, considerable progress has been made in characterising the neural
      circuitry of the pelvic plexus, particularly in the male rat. However, the small
      ganglia on the adventitial surface of the rectum remain largely unstudied. We
      have used immunohistochemistry and retrograde tracing techniques to determine the
      content and projections of these neurons. The adventitial ganglia contain 600
      1,000 neurons. All of these are immunoreactive for choline acetyltransferase, 44%
      are immunoreactive for calbindin, and 35% are immunoreactive for vasoactive
      intestinal peptide. Very few (1-5%) adventitial neurons contain tyrosine
      hydroxylase or neuropeptide Y. In contrast, most adventitial neurons are
      surrounded by varicose axons that do contain tyrosine hydroxylase or neuropeptide
      Y. Retrograde tracing studies showed that the primary targets of adventitial
      neurons within the bowel are the internal anal sphincter and the circular muscle
      directly adjacent to the sphincter. However, more adventitial neurons project out
      of the gut wall than to targets within the bowel. These are most likely to be
      viscerofugal and rectospinal neurons. Combining the immunohistochemical and
      tracing observations, these studies suggest that the rat adventitial ganglia do
      not represent an additional source of pelvic (autonomic postganglionic) neurons
      but, instead, that they are comprised primarily of viscerofugal and rectospinal
      neurons. This is very different from the adventitial rectal ganglia of the cat,
      which represent merely an extension of the pelvic plexus.

PMID- 9651004
TI  - Developmental changes in human cerebellum: expression of intracellular calcium
      receptors, calcium-binding proteins, and phosphorylated and nonphosphorylated
      neurofilament protein.
AB  - Few recent data are available on the development of the precise projection maps
      of the cerebellar cortex in humans. To address this topic, we studied temporal
      and spatial distribution of several antigens involved in calcium (Ca)-dependent
      processes: the intracellular Ca receptors, inositol 1,4,5-trisphosphate receptor
      type 1 (IP3R1) and ryanodine receptor (RyR); the Ca-binding proteins, calbindin D
      28k (CB), parvalbumin (PV), and synaptophysin; and phosphorylated (SMI 31) and
      nonphosphorylated (SMI 32) forms of neurofilament protein. All antigens were
      studied in the human cerebellum during intrauterine development. The results of
      this study show that immunocytochemical markers appeared in the following
      sequence: CB and both forms ofneurofilament protein were observed at 4-5
      gestational weeks (g.w.), PV appeared in the external granular layer and in a few
      Purkinje cells at 11 g.w., a diffuse immunostaining for IP3R1 and synaptophysin
      were observed at 13 g.w., whereas RyR was observed at 17-18 g.w. From 24 g.w. on,
      Purkinje cells expressed all four examined markers of intracellular Ca signaling
      as well as two forms of neurofilament protein. At the same time, compartmentation
      of the Purkinje cell layer was detected with three intracellular Ca-signaling
      molecules (IP3R1, CB, and PV) and with SMI 32. These results indicate that the
      developmentally regulated expression of antigens studied here may play a role in
      establishing a highly regular organization of terminal fields in the human
      cerebellar cortex. Moreover, the initial expression of these antigens is
      correlated temporally with other developmental processes in the cerebellum, such
      as cellular maturation, revealed by the immunoreaction to cytoskeletal protein,
      and synaptogenesis, revealed by immunoreaction to synaptophysin.

PMID- 9651005
TI  - Projections from substantia nigra and zona incerta to the cat's nucleus of
      Darkschewitsch.
AB  - The goal of the present experiments was to examine the relationships of the
      nucleus of Darkschewitsch (ND) with the substantia nigra pars reticulata (SNr),
      the zona incerta (ZI), and the oculomotor nuclei by using wheat germ agglutinin
      horseradish peroxidase (WGA-HRP) as a retrograde and anterograde neuronal tracer
      injected into various sites of the cat's brain. To eliminate the possibility that
      fibres of passage from the motor cortex passing through the SNr and ZI were
      responsible for the ND label, WGA-HRP also was injected into the SNr or the ZI
      after a large area of the frontal cortex, including the motor area, was
      destroyed. Retrograde axonal transport demonstrated that many cells of the
      rostromedial part of the ZI project to the ND, with the ipsilateral projections
      being dominant. Some cells of the caudomedial part of the SNr project to the ND,
      again, with the ipsilateral projection being dominant. A few small cells in the
      ND project bilaterally to the oculomotor nucleus. Anterograde tracer demonstrated
      that the SNr-ND terminal fields are less dense than the ZI-ND terminal fields. A
      few fine terminal fibres were observed bilaterally in the oculomotor, trochlear,
      and abducens nuclei. Electron microscopic examination demonstrated that these
      fine, labelled terminals contain pleomorphic vesicles and have symmetrical
      synaptic contacts with dendrites. These results indicate that the ND, a structure
      that is known to be important for the control of axial muscles (i.e., eye, head,
      and body muscles), is the target of projections from restricted areas of the SNr
      and ZI: areas that, during saccadic eye movement, may lead to disinhibition of
      the ND-oculomotor projection. Accordingly, the ND may function to inhibit the
      activity of extraocular muscles during saccades.

PMID- 9651006
TI  - Differences in developmental cell death between somatic and autonomic motor
      neurons of rat spinal cord.
AB  - Considerable knowledge concerning developmental cell death has come from the
      study of somatic motor neurons (SMNs), but a related set of spinal neurons, the
      autonomic motor neurons (AMNs), have been studied less extensively in this
      respect. In the present study, we used three different approaches to determine
      the amount of AMN cell death during normal development in the rat. First, target
      dependency was studied in organotypic slice cultures, and it was found that AMNs
      survived for at least 12 days after removal of their postsynaptic targets. No
      factors were added to the serum-free medium to substitute for the ablated
      targets, indicating that AMNs were able to survive without target-derived trophic
      factors. Such target-independent survival is not characteristic of neurons that
      undergo typical developmental cell death. Second, AMNs were counted in double
      stained choline acetyltransferase immunocytochemical and NADPH diaphorase
      histochemical preparations at ages (postnatal days 4-22) encompassing the period
      when AMN postsynaptic target cells undergo developmental death. Neuron numbers
      were essentially identical at all ages examined, indicating that no AMN cell
      death occurred postnatally. Finally, from embryonic day 13 to postnatal day 22,
      animals were analyzed by using terminal transferase-mediated nick-end labeling to
      identify dying cells. Many fewer labeled cells were observed among AMNs than
      among SMNs. Thus, all three approaches indicated that there is a significant
      SMN/AMN difference in developmental cell death. The phenotypic trait(s) that
      underlies this difference may also be important in the relative resistance of
      AMNs to pathological conditions that induce death of SMNs, e.g., those involved
      in amyotrophic lateral sclerosis and excitotoxicity.

PMID- 9651007
TI  - Area-specific laminar distribution of cortical feedback neurons projecting to cat
      area 17: quantitative analysis in the adult and during ontogeny.
AB  - Corticocortical pathways can be classified as feedback and feedforward, in part
      according to the laminar distribution of the parent cell bodies. Here, we have
      developed exhaustive sampling procedures to determine unambiguously this laminar
      distribution. This shows that individual extrastriate areas in the adult cat have
      highly stereotyped proportions of supragranular layer neurons with respect to the
      total population of neurons back-projecting to area 17. During development, these
      adult laminar patterns emerge from an initially uniform radial distribution
      through a process of selective reorganization, which is highly specific to each
      area. Injections of fluorescent retrograde tracers were made in area 17. In areas
      19, 20, posteromedial lateral suprasylvian area, and anteromedial lateral
      suprasylvian area, we defined a projection zone as the region containing
      retrogradely labeled neurons. In the neonate, counts of labeled neurons
      throughout the projection zones show constant percentages of 40% in the
      supragranular layers. During development, there is an area-specific reduction in
      the percentage of supragranular labeled neurons generating the laminar
      distributions characteristic of each area. Numbers of labeled neurons were
      estimated at different eccentricities of the projection zone. This finding
      indicates that during development there is a relative decrease in the numbers of
      labeled neurons of the periphery of the projection zone in the supragranular
      layers but not in the infragranular layers. This decrease is accompanied by a
      relative decrease in the dimensions of the supragranular projection zone with
      respect to the infragranular projection zone. These findings suggest that each
      extrastriate area precisely adjusts the proportions of supragranular layer
      neurons back-projecting to striate cortex in part by developmental changes in the
      divergence-convergence values of individual neurons. This shaping of
      corticocortical connectivity occurs relatively late in postnatal development and
      could, therefore, be under epigenetic control.

PMID- 9651008
TI  - Expression of differential immune factors in temporal cortex and cerebellum: the
      role of alpha-1-antichymotrypsin, apolipoprotein E, and reactive glia in the
      progression of Alzheimer's disease.
AB  - A variety of factors and processes have been implicated in the development and
      progression of the pathology of Alzheimer's Disease (AD), including amyloid
      fragment deposition, reactive gliosis, alpha-1-antichymotrypsin (ACT), and
      apolipoprotein E (APOE). Carriers of the APOE 4 allele have been shown to have an
      enhanced risk of developing AD, and the ACT signal peptide A/A genotype may
      modify the APOEepsilon4 risk. The protein products of these genes have been shown
      to enhance conversion of diffuse beta amyloid (Abeta) fibrils, which are found in
      diffuse plaques, to the fibrillar form found in neuritic plaques. In affected
      regions of AD brain, ACT and APOE colocalize with Abeta deposits and reactive
      microglia and astrocytes. We examined the regional distribution of ACT, APOE, and
      reactive glia in temporal cortex, where neuritic plaques are abundant, and
      cerebellum (in areas where diffuse plaques but not neuritic plaques accumulate)
      to examine the relationship of these markers to the deposition of Abeta. In
      temporal cortex, ACT and APOE staining was localized to plaque-like profiles,
      reactive astrocytes, and blood vessels; human leukocyte antigen-DR (HLA-DR) and
      glial fibrillary acidic protein (GFAP) staining revealed focal clusters of
      reactive microglia and astrocytes. In cerebellum, ACT and APOE immunoreactivity
      was never localized to plaque-like profiles but was weakly localized to
      unreactive astrocytes; weak HLA-DR and GFAP immunoreactivity was present on
      quiescent microglia throughout the cerebellum. The lack of fibrillar amyloid
      deposits in cerebellum, despite the presence of well-characterized markers
      thought to mediate the production of Abeta, suggests that this brain region may
      be lacking certain factors necessary for fibril formation or that the cerebellum
      responds differently to stimuli that successfully mediate inflammation in
      affected cortex.

PMID- 9651009
TI  - Comparison of cortically and subcortically controlled motor systems: I.
      Morphology of intracellularly filled rubrospinal neurons in rat and turtle.
AB  - The rat and turtle differ markedly in major structural features of the
      corticocerebellorubrospinal circuitry. Although both species have a well
      developed cerebellorubrospinal system, they differ in that a direct cerebral
      cortical input to the red nucleus is present only in the rat. The aim of the
      present study was to compare features of the soma and dendritic morphology of
      rubrospinal neurons that receive cortical input, as in rats, with those that do
      not, as in turtles. Intracellular Lucifer Yellow injections of neurons
      retrogradely labeled with Fast Blue in the rat or activity-dependent
      sulforhodamine-labeled neurons in the turtle were used to fill rubrospinal
      neurons in 150-200-microm-thick fixed sections. Images of filled neurons were
      imported into a computer to analyze quantitatively soma and dendritic morphology.
      The results show that rubrospinal soma size is slightly larger in the rat than in
      the turtle. However, analysis of the dendritic morphology, including total
      dendritic length, length of primary, secondary, and tertiary dendritic branches,
      and a Scholl analysis of dendritic branch intersections across concentric rings,
      demonstrated no significant differences between the two species. These findings
      suggest that the basic dendritic morphology of rubrospinal neurons may have been
      established early in phylogeny, preceding the evolution of cortical inputs.
      Alternatively, similar dendritic morphologies may have arisen due to the presence
      of other synapses in the turtle that occupy the sites of the cortical input in
      the rat. This comparative approach provides insights into the information
      processing capabilities of cortically versus subcortically controlled motor
      systems.

PMID- 9651010
TI  - Patterns of brainstem projection to the thalamic reticular nucleus.
AB  - To understand better how the brainstem may influence thalamocortical activity, we
      have examined the projection patterns of different brainstem nuclei to the
      thalamic reticular nucleus. Iontophoretic injections of biotinylated dextran were
      made into various nuclei of the brainstem (superior colliculus, periaqueductal
      grey matter, parabrachial nucleus, pedunculopontine tegmental nucleus,
      laterodorsal tegmental nucleus, substantia nigra, ventral tegmental area, and
      locus coeruleus) of Sprague-Dawley rats by using stereotaxic coordinates. Our
      results show that afferents from each brainstem nucleus make distinct zones
      within the reticular nucleus. For example, the superior colliculus projects
      largely to the dorsal parts of the reticular nucleus, whereas the
      pedunculopontine nucleus projects to the ventral parts of the reticular nucleus.
      The substantia nigra, on the other hand, projects to the ventrolateral edge of
      the reticular nucleus. We also examined the distribution of these brainstem
      afferents within the dorsal thalamus and compared these distributions with those
      seen in the reticular nucleus. We found three different patterns. First, a given
      brainstem nucleus projects to a particular dorsal thalamic nucleus as well as to
      the corresponding, functionally associated, reticular sector (e.g., from the
      substantia nigra). Second, a given brainstem nucleus projects to a particular
      dorsal thalamic nucleus but not to the corresponding reticular sector (e.g., from
      the superior colliculus). Finally, a given brainstem nucleus projects to a given
      reticular sector but not to the corresponding dorsal thalamic nucleus (e.g., from
      the midbrain reticular nucleus). In general, our results indicate that various
      brainstem nuclei project to particular territories of the thalamic reticular
      nucleus. Through these reticular projections, brainstem nuclei may influence
      distinct thalamocortical pathways in addition to those that are influenced by
      their direct projection to the dorsal thalamus.

PMID- 9651011
TI  - Patterns of connections between zona incerta and brainstem in rats.
AB  - To understand better the organisation of zona incerta of the thalamus, this study
      has examined the patterns of connections that this nucleus has with various
      nuclei of the brainstem. Injections of biotinylated dextran or cholera toxin
      subunit B were made into the dorsal raphe, midbrain reticular nucleus,
      pedunculopontine tegmental nucleus, periaqueductal grey matter, pontine reticular
      nucleus, substantia nigra, superior colliculus, and ventral tegmental area of
      Sprague-Dawley rats, and their brains were processed by using standard tracer
      detection methods. In general, our results show that zona incerta forms the major
      zone in the thalamus where these ascending brainstem axons terminate and from
      which descending axons that travel back to these same brainstem centres
      originate. These incertal inputs and outputs are limited largely to a distinct
      sector of zona incerta, the dorsal sector. An exception to this pattern is
      evident in the incertal projection to the deep layers of the superior colliculus;
      this projection, unlike all of the others, arises from cells in the ventral
      sector of zona incerta. Our results also show little evidence for a well-defined
      topography of projection between the brainstem and the zona incerta. For
      instance, small injections into each brainstem nucleus result in labelled
      terminals and in cells spread throughout much of the dorsal sector of zona
      incerta, with no local zone of concentration within the sector. Again, an
      exception to this pattern is seen in the incertal projection to the superior
      colliculus. This projection, unlike the others, shows a clear topographical
      organisation: A medial-lateral shift in the injection site in the colliculus
      results in a lateral-medial shift in the position of labelled cells in zona
      incerta. Curiously, even though the incertal projection to the colliculus appears
      to be mapped, the collicular projection back to zona incerta is not mapped. In
      conclusion, then, a number of brainstem nuclei (except for the deep collicular
      layers) have strong and overlapping connections within the same sector of zona
      incerta. This convergence of many functionally diverse brainstem afferents within
      zona incerta places this nucleus in a strategic position to sample the general
      activity of the brainstem and, perhaps, acts as a relay of this information to
      higher centres, such as the dorsal thalamic relay nuclei and the cerebral
      hemispheres.

PMID- 9651012
TI  - A model for the fluid motion of vitreous humour of the human eye during saccadic
      movement.
AB  - During saccadic motion the eyewall moves in a manner similar to a sinusoid or at
      least can be represented by a sine Fourier series. Motion of the vitreous is
      induced by the saccade and the vitreo-retinal interface is subjected to a time
      dependent shear. This force may be a significant factor for retinal tearing in
      the neighbourhood of small retinal holes or tears. An analytical viscoelastic
      model and a numerical, Newtonian model of the motion of the vitreous are
      presented and compared. Under sinusoidal boundary motion the analytical model
      shows that a viscous wave propagates inward toward the axis of rotation and the
      characteristic length of this wave is a function of the Womersley number. The
      numerical solution indicates that the vitreous moves similarly to the analytical
      result with small secondary motion; however, this motion allows complete
      recirculation of the vitreous over large timescales. Excellent agreement is found
      between the analytical and numerical models. The time-dependent fluid shear is
      evaluated and from the analytical solution the maximum value of this is found to
      be proportional to R0 square root of v(omega)3, where R0 is the eye radius, v the
      modified complex viscosity and omega the sinusoidal frequency. This indicates
      that myopes have a larger shear force exerted on them by virtue of the larger eye
      size. Further work is directed toward a model which links the stress found in the
      sclera to that exerted on the vitreo-retinal interface by the vitreous fluid
      motion.

PMID- 9651013
TI  - A data reduction scheme for improving the accuracy of oxygen saturation
      calculations from spectrometric in vivo measurements.
AB  - A developing tool in ophthalmological research and practice is the study of the
      oxygen saturation in retinal vessels because this measurement contains important
      diagnostic information about the metabolism at the human ocular fundus. Imaging
      spectrometry enables locally resolved measurements of the oxygen saturation
      simultaneously in arteries and veins. The vessel reflex, imaging errors of the
      detection system and the noise of the signal result in substantial uncertainties
      in the calculated data. We present a data processing method for the improvement
      of the primary information leading to a reduction of the uncertainties of the
      derived oxygen saturation.

PMID- 9651014
TI  - Monte Carlo simulation of source-excited in vivo x-ray fluorescence measurements
      of heavy metals.
AB  - This paper reports on the Monte Carlo simulation of in vivo x-ray fluorescence
      (XRF) measurements. Our model is an improvement on previously reported
      simulations in that it relies on a theoretical basis for modelling Compton
      momentum broadening as well as detector efficiency. Furthermore, this model is an
      accurate simulation of experimentally detected spectra when comparisons are made
      in absolute counts; preceding models have generally only achieved agreement with
      spectra normalized to unit area. Our code is sufficiently flexible to be applied
      to the investigation of numerous source-excited in vivo XRF systems. Thus far the
      simulation has been applied to the modelling of two different systems. The first
      application was the investigation of various aspects of a new in vivo XRF system,
      the measurement of uranium in bone with 57Co in a backscatter (approximately 180
      degrees) geometry. The Monte Carlo simulation was critical in assessing the
      potential of applying XRF to the measurement of uranium in bone. Currently the
      Monte Carlo code is being used to evaluate a potential means of simplifying an
      established in vivo XRF system, the measurement of lead in bone with 57Co in a 90
      degrees geometry. The results from these simulations may demonstrate that
      calibration procedures can be significantly simplified and subject dose may be
      reduced. As well as providing an excellent tool for optimizing designs of new
      systems and improving existing techniques, this model can be used in the
      investigation of the dosimetry of various XRF systems. Our simulation allows a
      detailed understanding of the numerous processes involved when heavy metal
      concentrations are measured in vivo with XRF.

PMID- 9651015
TI  - Electrochemical study of insulating properties of dental amalgam bonding
      polymers.
AB  - The standard techniques used for amalgam restorations often result in a lack of
      adhesion to mineralized dental tissues. The bonding of amalgam with polymer has
      been suggested to improve its adaptation to dental tissues. Moreover the polymer
      involved in the bonding should inhibit the corrosion and the diffusion of
      metallic ions. The aim of this study was to evaluate in vitro the capacity of
      bonded amalgam to prevent ionic diffusion and migration. In this respect, an
      original method employing electrochemical techniques was used to determine the
      leakage current of bonded amalgam restorations. The electrochemical behaviour of
      conventional and bonded amalgam restorations was compared using a potentiostat
      driven by a computerized system (Voltamaster, Radiometer Analytical) with
      software for specific applications such as chronoamperometry or cyclic
      voltammetry. Samples of recently extracted teeth of young patients were first
      examined, and then the results were checked by other experimental assays using
      protected and unprotected copper sticks. The measurements obtained with
      chronoamperometry (E = +300 mV/SCE) in Ringer's solution at 37 degrees C showed
      that after polarization for 30 h the oxidation current decreased threefold for
      bonded samples (10 microA cm(-2)) as compared with the unprotected samples (35
      microA cm(-2)). These results, as well as those obtained with the copper wires,
      demonstrated that even with two layers of adhesive the bonded joint is permeable
      to ions probably as a result of the hydrophylic properties of HEMA, a component
      of the adhesive. However, using five layers of adhesive reduced the ionic current
      by a factor as large as 10(6).

PMID- 9651016
TI  - A novel equivalent circuit model for gap-connected cells.
AB  - Gap junctions connect neighbouring cells, providing the intercellular
      communication that is essential for cell growth regulation, for example. There is
      some evidence that gap communication changes upon exposure to electromagnetic
      (EM) fields. In previous work, we performed detailed finite element method (FEM)
      modelling of gap junction connected cells exposed to EM fields. For cell
      configurations, the presence of gap junctions influences the transmembrane
      potential and its frequency behaviour. The relaxation frequency cannot be
      accurately predicted by previously developed simplified models. We present a
      novel equivalent circuit model (ECM) that incorporates more detailed models of
      the gaps, and compare results obtained with this ECM to finite element and leaky
      cable (LC) model results. Our ECM provides more accurate estimates of the
      frequency behaviour of cells than the leaky cable model. Also, our ECM results
      suggest limitations of the application of simple models to gap-connected cells:
      with higher gap resistivity, the current flow in the cell interiors becomes
      increasingly complex and is not well represented by simple models. In this case,
      techniques such as the finite element method are required to model accurately
      cell behaviour.

PMID- 9651017
TI  - Value of epicardial potential maps in localizing pre-excitation sites for
      radiofrequency ablation. A simulation study.
AB  - Using computer simulations, we systematically investigated the limitations of an
      inverse solution that employs the potential distribution on the epicardial
      surface as an equivalent source model in localizing pre-excitation sites in Wolff
      Parkinson-White syndrome. A model of the human ventricular myocardium that
      features an anatomically accurate geometry, an intramural rotating anisotropy and
      a computational implementation of the excitation process based on electrotonic
      interactions among cells, was used to simulate body surface potential maps
      (BSPMs) for 35 pre-excitation sites positioned along the atrioventricular ring.
      Two individualized torso models were used to account for variations in torso
      boundaries. Epicardial potential maps (EPMs) were computed using the L-curve
      inverse solution. The measure for accuracy of the localization was the distance
      between a position of the minimum in the inverse EPMs and the actual site of pre
      excitation in the ventricular model. When the volume conductor properties and
      lead positions of the torso were precisely known and the measurement noise was
      added to the simulated BSPMs, the minimum in the inverse EPMs was at 12 ms after
      the onset on average within 0.65 +/- 0.26 cm of the pre-excitation site. When the
      standard torso model was used to localize the sites of onset of the pre
      excitation sequence initiated in individualized male and female torso models, the
      mean distance between the minimum and the pre-excitation site was 0.67 +/- 0.31
      cm for the male torso and 0.82 +/- 0.53 cm for the female torso. The findings of
      our study indicate that a location of the minimum in EPMs computed using the
      inverse solution can offer non-invasive means for pre-interventional planning of
      the ablative treatment.

PMID- 9651018
TI  - Lung uptake of thallium-201: a marker of defect reversibility?
AB  - High lung uptake of thallium-201 at stress is reported to be associated with a
      large number of perfusion defects and poor prognosis. This study was performed to
      assess whether the reversibility of stress perfusion defects was related to lung
      uptake. Gated planar thallium scans at stress and at redistribution from 102
      consecutive patients with essentially normal left ventricular ejection fraction
      (using 99mTc gated blood pool ventriculography) were graded in terms of defect
      size. Lung and myocardial uptake of thallium were quantitated by region of
      interest methods relative to the given activity in a previously validated method.
      There was no significant correlation (non-parametric) between lung uptake and
      degree of redistribution (p = ns, rs = 0.140). There was a weak but positive
      correlation between lung uptake and defect size (p < 0.05, rs = 0.188). Both
      exercise time and double product showed a negative correlation with lung uptake
      (e.g. for double product, p < 0.0005, rs = -0.541). In conclusion, contrary to
      our expectation, lung uptake is not related to the degree of redistribution. High
      lung uptake seems to reflect poor cardiovascular reserve.

PMID- 9651019
TI  - Configuration options for intensity-modulated radiation therapy using multiple
      static fields shaped by a multileaf collimator. II: constraints and limitations
      on 2D modulation.
AB  - This paper addresses the technique of using multiple static multileaf-collimator
      shaped field components to create a two-dimensional intensity-modulated beam (2D
      IMB). It addresses the physical constraints on the problem of determining the
      optimum field-component leaf configurations under the circumstances that (i) the
      static field components are shaped by leaves alone and (ii) the 2D intensity
      distribution is delivered by exactly N field components when there are N rising
      intensity equal-fluence increments in the 1D channel containing the maximum
      fluence in the 2D IMB. This corresponds to the least inefficient delivery. In
      general it is noted that an optimum solution (set of field-component leaf
      configurations) with zero tongue-and-groove underdose may not exist (depending on
      the distribution) and an exhaustive search for the set of leaf configurations
      with the minimum tongue-and-groove underdose is impossible for realistically
      sized problems. Against this background iterative methods to examine a limited
      search space are shown to yield an optimum solution with zero tongue-and-groove
      underdose for certain intensity distributions. These searches are not robust and
      can be defeated. The problem of finding an optimum solution may be generally
      insoluble for some 2D IMBs under the conditions (i) and (ii). If, however, a
      larger number of field components is permitted and/or the accelerator jaws may
      also be used, in addition to the multileaves, then an optimum solution with zero
      tongue-and-groove underdose can always be found with lower efficiency.

PMID- 9651020
TI  - Calculation of absorbed dose distributions from dynamic wedges.
AB  - In radiotherapy with photon beams, the use of dynamic wedges, which are obtained
      by the movement of one of the jaws, offers an increasing flexibility relative to
      the traditional use of metal wedges. But it is a disadvantage for the measurement
      of absorbed dose distributions, because the absorbed dose at each measurement
      point can only be obtained after a complete movement of the jaw. Consequently,
      for radiotherapy planning, an algorithm should be available that does not require
      measurements for any specific dynamically wedged beam, but is based on only a
      modest number of measurements. In this paper, an algorithm for the calculation of
      the dose distribution from dynamic wedges is described. This algorithm uses the
      convolution of pencil beam kernels with a non-uniform field function. These
      pencil beam kernels are derived from empirical data resulting from measurements
      of the open beam only.

PMID- 9651021
TI  - Spectral reconstruction of clinical megavoltage photon beams and the implications
      of spectral determination on the dosimetry of such beams.
AB  - An analysis technique, based on simulated annealing, is described which is
      employed to derive megavoltage photon beam spectral information from narrow beam
      attenuation measurements. Megavoltage photon beam spectra have been determined
      using this technique for linear accelerators from different manufacturers, and
      different models from individual manufacturers at a range of energies from
      nominal 6 MV to nominal 25 MV. All of the photon beams included in the study are
      in routine clinical use. The subsequent effects on dosimetry of employing derived
      primary spectra to specify beam quality are examined. The results suggest that
      the quality index TPR(20)10 may be insensitive to beam quality changes for high
      energy beams in the range of 15 MV to 25 MV. Although the quality index may be
      insensitive as a beam quality specifier at these higher qualities, the actual
      difference in the calculated dose delivered using derived spectra as the quality
      specifier rather than TPR(20)10 is likely to be small, the results obtained
      indicating a difference of between 0.2% and 0.7% in the calculated dose
      delivered.

PMID- 9651022
TI  - An evaluation of epoxy resin phantom materials for electron dosimetry.
AB  - The use of epoxy resin 'solid water' (water substitute) phantoms is becoming
      increasingly common in radiotherapy dosimetry, and depth ionization curves and
      conversion factors from ionization to dose identical to water have often been
      assumed. Fluence ratios of water to solid water for WTe (produced by Radiation
      Physics, St Bartholomew's Hospital, London) and RMI 457 (produced by Radiation
      Measurements Inc., Middleton, Wisconsin) have therefore been determined and have
      been found to decrease with energy, which, within measurement uncertainty, can be
      described with a linear function dependent on mean electron beam energy at the
      depth of measurement, Ed. The fluence ratios for WTe are very close to unity
      (i.e. within the measuring uncertainty) for most of the energies examined, the
      exception being a nominal 20 MeV beam. The results also show that an assumption
      of unity for the fluence ratios of RMI 457 may introduce a systematic error of
      the order of 1% in electron beam dosimetry at lower energies. As regards the
      depth ionization curves measured in the respective solid water materials, these
      are shown to be in agreement with those measured in water within the limits of
      the measuring uncertainty.

PMID- 9651023
TI  - Dose accuracy check of the 3D electron beam algorithm in a treatment planning
      system.
AB  - The accuracy of the recently implemented three-dimensional electron beam dose
      calculating algorithm in CADPLAN version 2.62 manufactured by Varian Dosetek was
      investigated. The algorithm uses a generalized Gaussian pencil beam model and the
      dose distributions are calculated as the sum of three weighted Gaussians. To use
      the calculating program in an optimum way, one needs to know the dose calculation
      accuracy of the algorithm as well as its limitations. This investigation includes
      comparisons of measured relative dose distributions with calculated dose
      distributions and also comparisons of measured and calculated monitor units. The
      geometries tested were quadratic fields, irregularly shaped fields, oblique
      fields, irregularly shaped phantom surfaces and internal heterogeneities and were
      most often irradiated with 8 and 20 MeV electrons. The results indicate that the
      algorithm is well suited for clinical three-dimensional dose planning. Some
      deviations occurred but they were most often within the limits of international
      criteria of acceptability.

PMID- 9651024
TI  - Dose characteristics of in-house-built collimators for stereotactic radiotherapy
      with a linear accelerator.
AB  - Dose characteristics of a stereotactic radiotherapy unit based on a standard
      Varian Clinac 4/100 4 MV linear accelerator, in-house-built Lipowitz collimators
      and the SMART stereotactic radiotherapy treatment planning software have been
      determined. Beam collimation is constituted from the standard collimators of the
      linear accelerator and a tertiary collimation consisting of a replaceable
      divergent Lipowitz collimator. Four collimators with isocentre diameters of 15,
      25, 35 and 45 mm, respectively, were constructed. Beam characteristics were
      measured in air, acrylic or water with ionization chamber, photon diode, electron
      diode, diamond detector and film. Monte Carlo simulation was also applied. The
      radiation leakage under the collimators was less than 1% at 50 mm depth in water.
      Specific beam characteristics for each collimator were imported to SMART and dose
      planning with five non-coplanar converging 140 degrees arcs separated by 36
      degrees angles was performed for treatment of a RANDO phantom. Dose verification
      was made with TLD and radiochromic film. The in-house-built collimators were
      found to be suitable for stereotactic radiotherapy and patient treatments with
      this system are in progress.

PMID- 9651025
TI  - Dose rate constants for 125I, 103Pd, 192Ir and 169Yb brachytherapy sources: an
      EGS4 Monte Carlo study.
AB  - An exhaustive revision of dosimetry data for 192Ir, 125I, 103Pd and 169Yb
      brachytherapy sources has been performed by means of the EGS4 simulation system.
      The DLC-136/PHOTX cross section library, water molecular form factors, bound
      Compton scattering and Doppler broadening of the Compton-scattered photon energy
      were considered in the calculations. The absorbed dose rate per unit contained
      activity in a medium at 1 cm in water and air-kerma strength per unit contained
      activity for each seed model were calculated, allowing the dose rate constant
      (DRC) A to be estimated. The influence of the calibration procedure on source
      strength for low-energy brachytherapy seeds is discussed. Conversion factors for
      125I and 103Pd seeds to obtain the dose rate in liquid water from the dose rate
      measured in a solid water phantom with a detector calibrated for dose to water
      were calculated. A theoretical estimate of the DRC for a 103Pd model 200 seed
      equal to 0.669 +/- 0.002 cGy h(-1) U(-1) is obtained. Comparison of obtained DRCs
      with measured and calculated published results shows agreement within 1.5% for
      192Ir, 169Yb and 125I sources.

PMID- 9651026
TI  - Shuttle dose at the Vienna Leksell Gamma Knife.
AB  - The aim of this study was to determine the shuttle dose for all collimator
      helmets (4, 8, 14 and 18 mm) of the Gamma Knife, model B, in Vienna, Austria. The
      additional dose accumulated during the transport of the patient in and out of the
      treatment position should be considered in the dose planning procedure of
      multicentre treatment regimens and in fractionated stereotactic Gamma Knife
      radiotherapy. The GafChromic film study was basically used to determine the
      shuttle dose of all four collimator helmets. In addition, measurements with an
      ionization chamber (18 and 14 mm collimator--and, for the 18 mm collimator
      helmet, TLD dosimetry--were performed in order to confirm the GafChromic film
      data. The shuttle dose ranged between 99.6 and 183.5 mGy, depending mainly on the
      size of the collimator and the irradiated isocentres at the half-life activity of
      Co-60 in a brand new Gamma unit. Our film-generated data were in good correlation
      with the dose levels obtained with the ionization chamber and the TLD dosimetry,
      showing a dose difference of less than 0.8%. Since it was possible to verify the
      shuttle dose even for the 4 and 8 mm collimator helmets, we consider it a non
      negligible factor and would advocate the inclusion of the shuttle dose in
      radiosurgical dose planning.

PMID- 9651027
TI  - The precision of proton range calculations in proton radiotherapy treatment
      planning: experimental verification of the relation between CT-HU and proton
      stopping power.
AB  - The precision in proton radiotherapy treatment planning depends on the accuracy
      of the information used to calculate the stopping power properties of the tissues
      in the patient's body. This information is obtained from computed tomography (CT)
      images using a calibration curve to convert CT Hounsfield units into relative
      proton stopping power values. The validity of a stoichiometric method to create
      the calibration curve has been verified by measuring pairs of Hounsfield units
      and stopping power values for animal tissue samples. It was found that the
      agreement between measurement and calibration curve is better than 1% if beam
      hardening effects in the acquisition of the CT images can be neglected. The
      influence of beam hardening effects on the quantitative reading of the CT
      measurements is discussed and an estimation for the overall range precision of
      proton beams is given. It is expected that the range of protons in the human body
      can be controlled to better than +/-1.1% of the water equivalent range in soft
      tissue and +/-1.8% in bone, which translates into a range precision of about 1-3
      mm in typical treatment situations.

PMID- 9651028
TI  - The equivalent square concept for the head scatter factor based on scatter from
      flattening filter.
AB  - The equivalent field relationship between square and circular fields for the head
      scatter factor was evaluated at the source plane. The method was based on
      integrating the head scatter parameter for projected shaped fields in the source
      plane and finding a field that produced the same ratio of head scatter to primary
      dose on the central axis. A value of sigma/R approximately equal to 0.9 was
      obtained, where sigma was one-half of the side length of the equivalent square
      and R was the radius of the circular field. The assumptions were that the
      equivalent field relationship for head scatter depends primarily on the
      characteristics of scatter from the flattening filter, and that the differential
      scatter-to-primary ratio of scatter from the flattening filter decreases linearly
      with the radius, within the physical radius of the flattening filter. Lam and co
      workers showed empirically that the area-to-perimeter ratio formula, when applied
      to an equivalent square formula at the flattening filter plane, gave an accurate
      prediction of the head scatter factor. We have analytically investigated the
      validity of the area-to-perimeter ratio formula. Our results support the fact
      that the area-to-perimeter ratio formula can also be used as the equivalent field
      formula for head scatter at the source plane. The equivalent field relationships
      for wedge and tertiary collimator scatter were also evaluated.

PMID- 9651029
TI  - An adaptive control algorithm for optimization of intensity modulated
      radiotherapy considering uncertainties in beam profiles, patient set-up and
      internal organ motion.
AB  - A new general beam optimization algorithm for inverse treatment planning is
      presented. It utilizes a new formulation of the probability to achieve
      complication-free tumour control. The new formulation explicitly describes the
      dependence of the treatment outcome on the incident fluence distribution, the
      patient geometry, the radiobiological properties of the patient and the
      fractionation schedule. In order to account for both measured and non-measured
      positioning uncertainties, the algorithm is based on a combination of dynamic and
      stochastic optimization techniques. Because of the difficulty in measuring all
      aspects of the intra- and interfractional variations in the patient geometry,
      such as internal organ displacements and deformations, these uncertainties are
      primarily accounted for in the treatment planning process by intensity modulation
      using stochastic optimization. The information about the deviations from the
      nominal fluence profiles and the nominal position of the patient relative to the
      beam that is obtained by portal imaging during treatment delivery, is used in a
      feedback loop to automatically adjust the profiles and the location of the
      patient for all subsequent treatments. Based on the treatment delivered in
      previous fractions, the algorithm furnishes optimal corrections for the remaining
      dose delivery both with regard to the fluence profile and its position relative
      to the patient. By dynamically refining the beam configuration from fraction to
      fraction, the algorithm generates an optimal sequence of treatments that very
      effectively reduces the influence of systematic and random set-up uncertainties
      to minimize and almost eliminate their overall effect on the treatment. Computer
      simulations have shown that the present algorithm leads to a significant increase
      in the probability of uncomplicated tumour control compared with the simple
      classical approach of adding fixed set-up margins to the internal target volume.

PMID- 9651030
TI  - An optimized leaf-setting algorithm for beam intensity modulation using dynamic
      multileaf collimators.
AB  - A leaf-setting algorithm is developed for generating arbitrary beam intensity
      profiles in discrete levels using dynamic multileaf collimators (DMLCs). The
      algorithm starts with the algebraic expression for the area under the beam
      profile. It is shown that the coefficients in this expression can be transformed
      into the specifications for the leaf-setting sequence. It is proven that the
      algorithm optimizes beam delivery time and total monitor units for the DMLC leaf
      setting for intensity modulated radiotherapy (IMRT). The algorithm is
      demonstrated to be applicable to both the 'step-and-shoot' and 'dynamic' type of
      beam delivery. The graphical interpretation and numerical implementation scheme
      of the algorithm is illustrated using a simplified example.

PMID- 9651031
TI  - Registration of synthetic tomographic projection data sets using cross
      correlation.
AB  - Tomographic registration, a method that makes possible accurate patient
      registration directly from projection data, consists of three processing steps:
      (i) manual coarse positioning, (ii) tomographic projection set acquisition, and
      (iii) computer mediated refined positioning. In the coarse positioning stage, the
      degree of patient alignment is comparable with that achieved with the standard
      radiotherapy set-up. However, the accuracy requirements are somewhat more relaxed
      in that meticulous alignment of the patient using external laser indicators is
      not necessary. Instead, tomographic projection sets are compared with planning
      CTs in order to achieve improved patient set-up. The projection sets are cross
      correlated to obtain the best-fit translation and rotation offsets. The algorithm
      has been tested on synthetic data with the incorporation of varying amounts of
      Gaussian pseudo-random noise. These tests demonstrate the algorithm's stability
      and also confirm that alignment can be achieved with an accuracy of less than one
      projection pixel.

PMID- 9651032
TI  - A new method to estimate parameters of linear compartmental models using
      artificial neural networks.
AB  - At present, the preferred tool for parameter estimation in compartmental analysis
      is an iterative procedure; weighted nonlinear regression. For a large number of
      applications, observed data can be fitted to sums of exponentials whose
      parameters are directly related to the rate constants/coefficients of the
      compartmental models. Since weighted nonlinear regression often has to be
      repeated for many different data sets, the process of fitting data from
      compartmental systems can be very time consuming. Furthermore the minimization
      routine often converges to a local (as opposed to global) minimum. In this paper,
      we examine the possibility of using artificial neural networks instead of
      weighted nonlinear regression in order to estimate model parameters. We train
      simple feed-forward neural networks to produce as outputs the parameter values of
      a given model when kinetic data are fed to the networks' input layer. The
      artificial neural networks produce unbiased estimates and are orders of magnitude
      faster than regression algorithms. At noise levels typical of many real
      applications, the neural networks are found to produce lower variance estimates
      than weighted nonlinear regression in the estimation of parameters from mono- and
      biexponential models. These results are primarily due to the inability of
      weighted nonlinear regression to converge. These results establish that
      artificial neural networks are powerful tools for estimating parameters for
      simple compartmental models.

PMID- 9651033
TI  - Application of distance-dependent resolution compensation and post-reconstruction
      filtering for myocardial SPECT.
AB  - Compensation for distance-dependent resolution can be directly incorporated in
      maximum likelihood reconstruction. Our objective was to examine the effectiveness
      of this compensation using either the standard expectation maximization (EM)
      algorithm or an accelerated algorithm based on use of ordered subsets (OSEM). We
      also investigated the application of post-reconstruction filtering in combination
      with resolution compensation. Using the MCAT phantom, projections were simulated
      for 360 degrees data, including attenuation and distance-dependent resolution.
      Projection data were reconstructed using conventional EM and OSEM with subset
      size 2 and 4, with/without 3D compensation for detector response (CDR). Also post
      reconstruction filtering (PRF) was performed using a 3D Butterworth filter of
      order 5 with various cutoff frequencies (0.2-1.2 cycles cm(-1)). Image quality
      and reconstruction accuracy were improved when CDR was included. Image noise was
      lower with CDR for a given iteration number. PRF with cutoff frequency greater
      than 0.6 cycles cm(-1) improved noise with no reduction in recovery coefficient
      for myocardium but the effect was less when CDR was incorporated in the
      reconstruction. CDR alone provided better results than use of PRF without CDR.
      Results suggest that using CDR without PRF, and stopping at a small number of
      iterations, may provide sufficiently good results for myocardial SPECT. Similar
      behaviour was demonstrated for OSEM.

PMID- 9651034
TI  - Statistical distribution of factors and factor images in factor analysis of
      medical image sequences.
AB  - From a time or energy image sequence, factor analysis of medical image sequences
      (FAMIS) estimates factors, representing kinetics or spectra in a given
      physiological compartment, and associated factor images, showing the compartments
      corresponding to each curve. In this paper, we show that the statistical
      properties of factor images and associated factors can be determined using a well
      known result from elementary probability theory. Numerical experiments are
      conducted to demonstrate that the variance observed in factor images can be
      predicted when the statistical properties of the original data are known. It is
      shown how these theoretical results can be used to relax the non-negativity
      constraints during FAMIS oblique analysis and to improve the quantitative
      interpretation of the factor images by associating a confidence interval with
      each pixel value.

PMID- 9651035
TI  - Selection of task-dependent diffusion filters for the post-processing of SPECT
      images.
AB  - Iterative reconstruction from single photon emission computed tomography (SPECT)
      data requires regularization to avoid noise amplification and edge artefacts in
      the reconstructed image. This is often accomplished by stopping the iteration
      process at a relatively low number of iterations or by post-filtering the
      reconstructed image. The aim of this paper is to develop a method to
      automatically select an optimal combination of stopping iteration number and
      filters for a particular imaging situation. To this end different error measures
      between the distribution of a phantom and a corresponding filtered SPECT image
      are minimized for different iteration numbers. As a study example, simulated data
      representing a brain study are used. For post-reconstruction filtering, the
      performance of 3D linear diffusion (Gaussian filtering) and edge preserving 3D
      nonlinear diffusion (Catte scheme) is investigated. For reconstruction methods
      which model the image formation process accurately, error measures between the
      phantom and the filtered reconstruction are significantly reduced by performing a
      high number of iterations followed by optimal filtering compared with stopping
      the iterative process early. Furthermore, this error reduction can be obtained
      over a wide range of iteration numbers. Only a negligibly small additional
      reduction of the errors is obtained by including spatial variance in the filter
      kernel. Compared with Gaussian filtering, Catte diffusion can further reduce the
      error in some cases. For the examples considered, using accurate image formation
      models during iterative reconstruction is far more important than the choice of
      the filter.

PMID- 9651036
TI  - Electrical impedance tomography with compensation for electrode positioning
      variations.
AB  - Ideally electrical impedance tomography (EIT) should not be oversensitive to
      electrode positions, but this conflicts with efforts to produce high-resolution
      images. Two procedures are presented that balance reducing the sensitivity to
      electrode position errors with generating practicable EIT images. The first
      provides a criterion based on electrode sensitivity for regularizing the
      reconstruction through spectral expansion. The main consequences of this are that
      smoother images are produced and the number of artefacts and their magnitude are
      generally reduced. The second modification uses the recorded data to compensate
      for electrode movements that have occurred after the reference data were
      measured. Image smoothness is used as the criterion for the readjustment.
      Computer simulation tests have shown that this modification produces improved
      image fidelity.

PMID- 9651037
TI  - Site-specific confocal fluorescence imaging of biological microstructures in a
      turbid medium.
AB  - Normally transparent biological structures in a turbid medium are imaged using a
      laser confocal microscope and multiwavelength site-specific fluorescence
      labelling. The spatial filtering capability of the detector pinhole in the
      confocal microscope limits the number of scattered fluorescent photons that reach
      the photodetector. Simultaneous application of different fluorescent markers on
      the same sample site minimizes photobleaching by reducing the excitation time for
      each marker. A high-contrast grey-level image is also produced by summing
      confocal images of the same site taken at different fluorescence wavelengths.
      Monte Carlo simulations are performed to obtain the quantitative behaviour of
      confocal fluorescence imaging in turbid media. Confocal images of the following
      samples were also obtained: (i) 15 microm diameter fluorescent spheres placed
      1.16 mm deep beneath an aqueous suspension of 0.0823 microm diameter polystyrene
      latex spheres, and (ii) hindbrain of a whole-mount mouse embryo (age 10 days)
      that was stained to fluoresce at 515 nm and 580 nm peak wavelengths. Expression
      of RNA transcripts of a gene within the embryo hindbrain was detected by a
      fluorescence-based whole-mount in situ hybridization procedure that we recently
      tested.

PMID- 9651038
TI  - A two-compartment phantom for VOI profile measurements in small-bore 31P MR
      spectroscopy.
AB  - A two-compartment gel phantom for VOI profile measurements in volume-selective
      31P spectroscopy in small-bore units is presented. The phantom is cylindrical
      with two compartments divided by a very thin (30 microm) polyethene film. This
      thin film permits measurements with a minimum of susceptibility influences from
      the partition wall. The phantom was used for evaluation of the volume selection
      method ISIS (image-selected in vivo spectroscopy). The position of the phantom
      was fixed in the magnet during the measurements, while the volume of interest
      (VOI) was moved stepwise over the border. The signal from the two compartments
      was measured for each position and the data were evaluated following
      differentiation. We have found this phantom suitable for VOI profile measurements
      of ISIS in small-bore systems. The phantom forms a useful complement to
      recommended phantoms for small bore-spectroscopy.

PMID- 9651039
TI  - Determination of the wavelength dependence of the differential pathlength factor
      from near-infrared pulse signals.
AB  - For the calculation of changes in oxyhaemoglobin, deoxyhaemoglobin and the redox
      state of cytochrome-c-oxidase from attenuation data via a modified Beer-Lambert
      equation the wavelength dependence of the differential pathlength factor
      (DPF(lambda)) has to be taken into account. The DPF, i.e. the ratio of the mean
      optical pathlength and the physical light source-detector separation at each
      wavelength, determines the crosstalk between the different concentrations and is
      therefore essential for a sensitive detection of chromophore changes. Here a
      simple method is suggested to estimate the wavelength dependence of the
      DPF(lambda) from pulse-induced attenuation changes measured on the head of adult
      humans. The essence is that the DPF is the ratio of the attenuation changes over
      absorption coefficient changes, and that the spectral form of the pulse
      correlated absorption coefficient change can be assumed to be proportional to the
      extinction coefficient of blood. Indicators for the validity of the DPF(lambda)
      derived for wavelengths between 700 and 970 nm are the stability of the
      calculated haemoglobin and cytochrome signals with variations of the wavelength
      range included for their calculation and its overall agreement with the data
      available from the literature.

PMID- 9651041
TI  - Characteristics of a commercially available film digitizer and their significance
      for film dosimetry.
AB  - Dosimetric detectors used in high-energy photon radiation dosimetry mainly
      perform a zero- or one-dimensional measurement. These low-dimensional methods are
      not always adequate in the context of conformal radiotherapy. Therefore, two
      dimensional film dosimetry has attracted attention. We studied a 12-bit CCD-based
      film digitizer (Vidar VXR-12) with regard to accurate film dosimetry. We
      investigated the stability, linearity, noise, effects of aberrant light scatter
      and built-in conversion tables. A digitizing resolution of 75 dpi and a
      digitizing speed of 20 ms/line result in an optimal signal-to-noise ratio. At
      optical densities above 2.0, the reading accuracy of the digitizer is limited by
      noise. The results of various experiments prove both the capabilities and
      limitations of the digitizer studied. We also propose a method to acquire and
      process film data using such a digitizer.

PMID- 9651040
TI  - Application of the Monte Carlo integration (MCI) method for calculation of the
      anisotropy of 192Ir brachytherapy sources.
AB  - Source anisotropy is a very important factor in the brachytherapy quality
      assurance of high-dose rate (HDR) 192Ir afterloading stepping sources. If
      anisotropy is not taken into account then doses received by a brachytherapy
      patient in certain directions can be in error by a clinically significant amount.
      Experimental measurements of anisotropy are very labour intensive. We have shown
      that within acceptable limits of accuracy, Monte Carlo integration (MCI) of a
      modified Sievert integral (3D generalization) can provide the necessary data
      within a much shorter time scale than can experiments. Hence MCI can be used for
      routine quality assurance schedules whenever a new design of HDR or PDR 192Ir is
      used for brachytherapy afterloading. Our MCI calculation results are compared
      with published experimental data and Monte Carlo simulation data for
      microSelectron and VariSource 192Ir sources. We have shown not only that MCI
      offers advantages over alternative numerical integration methods, but also that
      treating filtration coefficients as radial distance-dependent functions improves
      Sievert integral accuracy at low energies. This paper also provides anisotropy
      data for three new 192Ir sources, one for the microSelectron-HDR and two for the
      microSelectron-PDR, for which data are currently not available. The information
      we have obtained in this study can be incorporated into clinical practice.

PMID- 9651042
TI  - Photon dose calculations in homogeneous media for a treatment planning system
      using a collapsed cone superposition convolution algorithm.
AB  - This work reports on some of the initial tests that were conducted during the
      commissioning of a commercially available 3D treatment planning system. The
      system (Pinnacle 3.0d-u1) uses a collapsed cone implementation of the
      superposition convolution algorithm. Calculated and measured dose in homogeneous
      media were compared for wedged and unwedged fields for both symmetric and
      asymmetric collimator settings. Results show agreement of 2% or 2 mm in most
      cases. Where larger differences were found, further investigation was undertaken
      to explain these differences. These tests demonstrate the correct behaviour of
      the collapsed cone implementation of the algorithm in homogeneous media and its
      ability to characterize the beam.

PMID- 9651043
TI  - The FEMA GRAS assessment of lactones used as a flavour ingredients. The Flavor
      and Extract Manufacturers' Association. Generally recognized as safe.

PMID- 9651044
TI  - Heterocyclic amine content in beef cooked by different methods to varying degrees
      of doneness and gravy made from meat drippings.
AB  - Meats cooked at high temperatures sometimes contain heterocyclic amines (HCAs)
      that are known mutagens and animal carcinogens, but their carcinogenic potential
      in humans has not been established. To investigate the association between HCAs
      and cancer, sources of exposure to these compounds need to be determined. Beef is
      the most frequently consumed meat in the United States and for this study we
      determined HCA values in beef samples cooked in ways to represent US cooking
      practices, the results of which can be used in epidemiological studies to
      estimate HCA exposure from dietary questionnaires. We measured five HCAs [2-amino
      3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline
      (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8
      trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP)] in different types of cooked beef using
      solid-phase extraction and HPLC. Steak and hamburger patties were pan-fried, oven
      broiled, and grilled/barbecued to four levels of doneness (rare, medium, well
      done or very well done), while beef roasts were oven cooked to three levels of
      doneness (rare, medium or well done). The measured values of the specific HCAs
      varied with the cut of beef, cooking method, and doneness level. In general,
      MeIQx content increased with doneness under each cooking condition for steak and
      hamburger patties, up to 8.2 ng/g. PhIP was the predominant HCA produced in steak
      (1.9 to 30 ng/g), but was formed only in very well done fried or grilled
      hamburger. DiMeIQx was found in trace levels in pan-fried steaks only, while IQ
      and MeIQ were not detectable in any of the samples. Roast beef did not contain
      any of the HCAs, but the gravy made from the drippings from well done roasts had
      2 ng/g of PhIP and 7 ng/g of MeIQx. Epidemiological studies need to consider the
      type of meat, cooking method and degree of doneness/surface browning in survey
      questions to adequately assess an individual's exposure to HCAs.

PMID- 9651045
TI  - Heterocyclic amine content of pork products cooked by different methods and to
      varying degrees of doneness.
AB  - Heterocyclic amines (HCAs) are known mutagens and animal carcinogens produced in
      meats cooked at high temperature. As pork is the second most frequently consumed
      meat in the United States, five predominant HCAs [2-amino-3-methylimidazo[4,5
      f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8
      dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4.5
      f]quinoxaline (DiMeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
      (PhIP)] were measured in various pork products, cooked by different techniques
      and to varying doneness levels. Pork chops and ham slices were pan-fried and oven
      broiled; bacon was pan-fried, oven-broiled or microwaved; hot dogs were pan
      fried, oven-broiled, grilled/barbecued or boiled; sausage links and patties were
      pan-fried. All the products were cooked to three levels of doneness: just until
      done, well done or very well done. HCA type and level varied substantially by
      pork product, cooking method and doneness level. The highest PhIP levels were
      found in well done and very well done oven-broiled bacon; for very well done 30.3
      and 4.0 ng per gram of meat of PhIP and MeIQx, respectively. Pan-fried very well
      done sausage patties contained 5.4 ng of MeIQx per gram of meat, while sausage
      links contained 1.3 ng per gram of meat. MeIQx was formed in well done and very
      well done pan-fried but not broiled pork chops. Hot dogs or ham slices had low or
      undetectable levels of HCAs. These results demonstrate that epidemiological
      studies investigating the relationship between HCA intake and cancer risk need to
      incorporate type of meat, cooking method and degree of doneness/surface browning
      into questions to assess adequately an individual's HCA exposure.

PMID- 9651046
TI  - Variation in susceptibility to the induction of forestomach tumours by butylated
      hydroxyanisole among rats of different strains.
AB  - The forestomach carcinogenicity of butylated hydroxyanisole (BHA) was compared in
      males of the F344, SHR, Lewis and Sprague Dawley rat strains. Groups of 30 6-wk
      old animals were given a pellet diet containing 2% BHA for 104 wk. Forestomach
      squamous cell papillomas and hyperplasias developed in all rats given BHA,
      independent of the strain, but the incidences of squamous cell carcinomas (SCCs)
      differed considerably: F344, 26.7% (8/30) SHR, 76.7% (23/30) SD, 36.7% (1130)
      Lewis, 6.7% (2/30). Cytotoxic effects, reflected by inflammation, were also most
      severe in the SHR strain, correlating well with the development of SCCs. The
      present results indicate that major strain differences exist regarding BHA rat
      forestomach carcinogenesis and that sensitivity to cytotoxicity might be an
      important parameter.

PMID- 9651047
TI  - Identification of 2,5-dimethyl-4-hydroxy-3(2H)-furanone (DMHF) and 4-hydroxy-2(or
      5)-ethyl-5(or 2)-methyl-3(2H)-furanone (HEMF) with DNA breaking activity in soy
      sauce.
AB  - Components with DNA breaking activity in soy sauce were investigated. It was
      found that there were water soluble high molecular weight DNA breaking components
      in soy sauce. Two DNA breaking components in the ethyl acetate extract of soy
      sauce were identified as fragrant components, 2,5-dimethyl-4-hydroxy-3(2H)
      furanone (DMHF) and 4-hydroxy-2(or 5)-ethyl-5(or 2)-methyl-3(2H)-furanone (HEMF),
      in addition to the previously characterized DNA breaking fragrant component 4
      hydroxy-5-methyl-3(2H)-furanone (HMF) (Hiramoto et al., 1996b). Characterization
      of DNA breaking activity of HEMF was performed, and the mechanisms for the
      breaking were considered. HEMF cleaved the single strands of supercoiled pBR 322
      DNA at pH 7.4 dose dependently and time dependently. DNA breaking was inhibited
      by superoxide dismutase, catalase, hydroxyl radical scavengers, spin trapping
      agents and metal chelators, and enhanced by Fe(III) ion. Electron spin resonance
      spin trapping technique revealed the generation of hydroxyl radical. Hence,
      active oxygen species derived from interaction of HEMF with metal ions and oxygen
      participated in the cleavage. HEMF exhibited mutagenicity to Salmonella
      typhimurium TA100 without metabolic activation and induced micronucleated mouse
      peripheral reticulocytes.

PMID- 9651048
TI  - Effect of baking and freeze-drying on the direct and indirect mutagenicity of
      extracts from the edible mushroom Agaricus bisporus.
AB  - The objectives of the study were to evaluate the effect of baking and freeze
      drying on the direct and indirect mutagenicity in the Ames test of ethanolic
      extracts from the edible mushroom Agaricus bisporus. Direct mutagenicity was not
      influenced by baking for 10 min at 225 degrees C, but more prolonged baking, for
      example 4 hr at 100 degrees C reduced mutagenicity. Hepatic cytosol from Aroclor
      1254-induced rats and mushroom tyrosinase potentiated the mutagenic response
      elicited by the mushroom extracts. Baking did not influence either of these
      processes. Finally, freeze-drying influenced neither the direct nor the indirect
      mutagenicity of the mushroom extracts. It is concluded that mutagenic and
      premutagenic compounds present in mushroom are generally not heat labile.

PMID- 9651049
TI  - Ability of dairy strains of lactic acid bacteria to bind a common food
      carcinogen, aflatoxin B1.
AB  - This study was conducted to examine the ability of selected dairy strains of
      lactic acid bacteria to remove aflatoxin B1 (AFB1) from liquid media. Both
      Lactobacillus rhamnosus strain GG (LBGG) and L. rhamnosus strain LC-705 (LC705)
      can significantly (P > 0.05) remove AFB1 when compared with that by other strains
      of either Gram-positive or Gram-negative bacteria. Removal of AFB1 by LBGG and
      LC705 was a rapid process with approximately 80% AFB1 removed at 0 hr. Removal of
      AFB1 by these two strains was both temperature and bacterial concentration
      dependent.

PMID- 9651050
TI  - Strategies for identifying false positive responses in predictive skin
      sensitization tests.
AB  - It is important that predictive toxicological test methods are selective for
      their intended endpoint and that their limitations are understood and
      acknowledged. The local lymph node assay (LLNA) is a relatively new predictive
      test for skin sensitization potential that can replace traditional guinea pig
      tests and offers significant scientific and animal welfare advantages. However,
      there has been some concern that certain irritant materials may yield false
      positive results, although it must be emphasized that false positives also occur
      in guinea pig methods. Consequently, we have examined the performance in the LLNA
      of a range of skin irritants, from varying chemical classes and covering a range
      of irritation potency. The results presented here demonstrate clearly that the
      majority of skin irritants are negative in the LLNA. These results are reviewed
      in the context of the occurrence of false positive reactions in the guinea pig
      maximization test and the strategies for dealing with such results are discussed.
      The need for careful scientific evaluation of the results in all predictive tests
      for sensitization is thus emphasized. In terms of specificity, the LLNA has been
      more fully evaluated than other predictive test methods and is at least as
      accurate. In terms of animal welfare, objectivity, reproducibility and
      reliability it is superior to other methods. In summary, all predictive skin
      sensitization test results should be evaluated in a scientifically rigorous
      manner and the additional data provided herein further support the adoption of
      the LLNA as a complete replacement for the traditional guinea pig methods.

PMID- 9651051
TI  - Biochemistry and toxicology of the diterpenoid glycoside atractyloside.
AB  - Atractyloside (Atr) is a diterpenoid glycoside that occurs naturally in plants
      (many of which are used in ethnomedicines) found in Europe, Africa, South
      America, Asia and the far East. It is also present in animal grazing forage. Atr
      (and its analogues) may be present at levels as high as 600 mg/kg dried plant
      material. Consumption of the plants containing Atr or carboxyatractyloside
      (carboxyAtr) has caused fatal renal proximal tubule necrosis and/or centrilobular
      hepatic necrosis in man and farm animals. Although pure Atr and crude plant
      extracts disrupt carbohydrate homeostasis and induce similar pathophysiological
      lesions in the kidney and liver, it is also possible that the toxicity of Atr may
      be confounded by the presence of other natural constituents in plants. Atr
      competitively inhibits the adenine nucleoside carrier in isolated mitochondria
      and thus blocks oxidative phosphorylation. This has been assumed to explain
      changes in carbohydrate metabolism and the toxic effects in liver and kidney.
      Although the acute toxicity of Atr is well described, many aspects of Atr
      toxicity (subchronic and chronic toxicity, reproductive toxicity, mutagenicity
      and carcinogenicity) have not been investigated and pharmacokinetic and
      metabolism data are limited. In vitro proximal tubular cells are selectively
      sensitive to Atr, whereas other renal cell types are quite resistant. There are
      also differences in the response of liver and renal tissue to Atr. Thus, not all
      of the clinical, biochemical and morphological changes caused by Atr can simply
      be explained on the basis of inhibition of mitochondrial phosphorylation. The
      relevance to a wider human risk is shown by the presence of Atr analogues in
      dried roasted Coffea arabica beans (17.5 32 mg/kg). There are no data to help
      identify the risk of low dose chronic exposure in human coffee consumers, nor is
      there information on the levels of Atr or its analogues in other commonly
      consumed human foodstuffs.

PMID- 9651052
TI  - Review of the biological properties and toxicity of bee propolis (propolis).
AB  - Propolis is a multifunctional material used by bees in the construction and
      maintenance of their hives. Use of propolis by humans has a long history,
      predated only by the discovery of honey. Use of products containing propolis have
      resulted in extensive dermal contact and it is now increasingly being used a
      dietary supplement. Unlike many 'natural' remedies, there is a substantive
      database on the biological activity and toxicity of propolis indicating it may
      have many antibiotic, antifungal, antiviral and antitumour properties, among
      other attributes. Although reports of allergic reactions are not uncommon,
      propolis is relatively non-toxic, with a no-effect level (NOEL) in a 90-mouse
      study of 1400 mg/kg body weight/day.

PMID- 9651053
TI  - The role of the radiologist in breast diagnosis: a surgeon's personal view.

PMID- 9651054
TI  - Pulmonary arteriovenous malformations.
AB  - Pulmonary arteriovenous malformations (PAVMs) are uncommon lesions, but are the
      cause of considerable morbidity and occasional mortality. They most commonly
      occur in association with hereditary haemorrhagic telangectasia and screening of
      families with this condition is therefore important. Embolization of PAVMs by
      coils is a well tolerated effective procedure with a low complication rate in
      skilled hands. Treatment results in both symptomatic and physiological
      improvement, and evidence for a reduction in stroke and cerebral abscess is
      accumulating. Radiological techniques now represent the primary treatment of
      choice, with surgical resection rarely required.

PMID- 9651055
TI  - Radiology of the jugular foramen.
AB  - The jugular foramen, a complex bony canal, transmits vessels and nerves from the
      posterior cranial fossa through the skull base into the carotid space. It is
      inaccessible to clinical examination and radiology plays a central role in
      evaluating this region. Familiarity with the normal anatomy of this area will
      help in the formulation of differential diagnosis and the assessment of disease
      extent. Both intracranial and extracranial lesions may affect the jugular foramen
      in addition to intrinsic abnormalities. Normal variants and artefacts seen on
      magnetic resonance imaging (MRI) should not be mistaken for pathological
      processes.

PMID- 9651056
TI  - CT appearances and prognostic significance of splenic metastasis in ovarian
      cancer.
AB  - DESIGN: A retrospective review of women undergoing computed tomography (CT) as
      part of the investigation and management of pathologically proven ovarian cancer
      in a single specialist gynaecological cancer centre. OBJECTIVE: To ascertain CT
      appearances and prognostic significance of splenic involvement in ovarian cancer.
      RESULTS: We found a 10.3% frequency of splenic metastasis in a series of 321
      patients with ovarian cancer. Thirty-three women had splenic metastases
      demonstrated on CT. Twenty-three women had surface lesions with an irregular
      scalloped shape and broad contact with the splenic surface; 17 of these women had
      lesions at presentation. Ten women had parenchymal lesions, five at presentation
      and five at relapse, typically with a rounded shape surrounded by normal splenic
      tissue. Four out of 10 cases with parenchymal involvement showed lesion
      progression during chemotherapy. However, lesion progression occurred in only one
      of 23 cases with surface disease (P < 0.025, Fisher's exact test). In 16 cases
      with disease involving both spleen and liver, the response to chemotherapy was
      the same in both organs. CONCLUSION: We have found a higher frequency of splenic
      metastasis from ovarian cancer during life than previously reported. Parenchymal
      lesions are significantly less likely to respond to treatment than surface
      lesions but are more commonly a feature of relapsed disease. We have demonstrated
      that splenic metastases behave similarly to liver metastases in ovarian cancer.
      We suggest that the presence of splenic parenchymal metastasis is indicative of
      FIGO stage IV disease. This finding has implications for proposed cytoreductive
      surgery.

PMID- 9651057
TI  - Correlation of CT with histopathological findings in patients with gastric and
      gastro-oesophageal carcinomas following neoadjuvant chemotherapy.
AB  - Gastric carcinoma is the fourth commonest cause of death from malignant disease
      in United Kingdom. In the Western hemisphere, it usually presents with advanced
      disease, which contributes to its very poor prognosis. Pre-operative
      (neoadjuvant) chemotherapy offers the possibility of down-staging such tumours
      and the potential to render tumours operable. Computed tomography (CT) plays a
      central role in the assessment of patients presenting with the disease, and in
      those who undergo chemotherapy, in evaluating their response. OBJECTIVE: This
      study was undertaken to evaluate the role of CT in predicting loco-regional
      spread of tumour following neoadjuvant chemotherapy in non-metastatic gastric and
      gastro-oesophageal cancers. METHODS AND MATERIALS: We correlated CT evidence of
      loco-regional spread with pathological findings following surgery in 21 patients
      who received pre-operative chemotherapy. RESULTS: Residual masses were seen on CT
      in 19 patients, and 15 contained active tumour, although in four patients no
      viable tumour was demonstrated at histopathology. The overall accuracy of CT in
      assessing loco-regional disease was disappointing with sensitivities,
      specificities, positive and negative predictive values of 57%, 43%, 75% and 33%,
      respectively. CONCLUSIONS: We conclude that CT is not accurate in identifying
      residual loco-regional spread and therefore should not preclude surgery in those
      patients who have received neoadjuvant chemotherapy.

PMID- 9651058
TI  - Characterization of primary intracranial lymphoma by computed tomography: an
      analysis of 36 cases and a review of the literature with particular reference to
      calcification haemorrhage and cyst formation.
AB  - Previous published series describing the appearances of primary central nervous
      system lymphoma (PCNSL) state that calcification, haemorrhage and cyst formation
      are rare, but generally fail to quantify or expand on this statement. We present
      the pre-treatment computed tomography (CT) findings of 36 patients with biopsy
      proven PCNSL. In this series, calcification was present in only one very atypical
      lesion and evidence of haemorrhage was not seen. Small intralesional cysts were
      present in four of the total of 50 lesions. PCNSL usually appeared as one or more
      well defined focal lesions, iso- or hyperdense to grey matter, with homogeneous
      enhancement following IV contrast injection. Less commonly the contrast
      enhancement was inhomogeneous, only one lesion failed to enhance.
      Disproportionately little oedema and mass effect compared with lesion size was
      noted on approximately half the CTs. Lesions usually touch either the ependymal
      lining of the ventricles or the leptomeningeal surface.

PMID- 9651059
TI  - Mediastinal lymphadenopathy in cryptogenic fibrosing alveolitis: the effect of
      steroid therapy on the prevalence of nodal enlargement.
AB  - PURPOSE: To determine the prevalence of enlarged mediastinal lymph nodes in
      cryptogenic fibrosing alveolitis (CFA) and to assess whether this frequency was
      related to steroid administration. MATERIAL AND METHODS: Retrospective review of
      chest radiographs and high-resolution computed tomography (CT) of 54 patients
      with proven cryptogenic fibrosing alveolitis (CFA). Twenty-two of the 54 patients
      received oral steroids up to 2 months before the time of high-resolution CT
      examination (group 1); the remaining 32 patients had not taken steroids for at
      least 6 months before study entry (group 2). The prevalence, distribution, and
      size of enlarged mediastinal lymph nodes was determined in all groups. The
      diagnosis of CFA was histologically established in 44 patients. In 10 patients
      the diagnosis of CFA was based on clinical and high-resolution CT findings.
      RESULTS: Mediastinal lymphadenopathy was present in 26 of 54 patients with CFA.
      The prevalence of enlarged nodes was 14% (three of 22) in patients who had
      received oral steroids up to 2 months before the time of CT examination, and 71%
      (23 of 32) in patients that had not taken steroids for at least 6 months before
      study entry. CONCLUSION: We conclude that patients with CFA on steroid therapy
      had a significantly lower prevalence of mediastinal adenopathy (P < 0.001) than
      patients who had not taken steroids.

PMID- 9651060
TI  - The effect of angiographic technique and image quality on the reproducibility of
      measurement of carotid stenosis and assessment of plaque surface morphology.
AB  - We studied the reproducibility of measurement of carotid stenosis and assessment
      of plaque surface morphology on 1001 angiograms from a consecutive series of
      patients entered into the European Carotid Surgery Trial. Inter-observer
      agreement (Kappa statistic, 95% confidence interval (CI)) for categorization of
      carotid stenosis, as 0-29%, 30-69% or 70-99% was good (0.68, 0.63-0.73) on 789
      conventional or digitally subtracted selective angiograms, and good (0.64, 0.54
      0.75) on 174 conventionally and digitally subtracted aortic arch injection
      angiograms, but was poor (0.29, 0.02-0.80) on 29 intravenous digital subtraction
      angiograms. Inter-observer agreement did not vary with the method of image
      acquisition of arterial angiograms, but was dependent on the quality of
      visualization of the stenosis: kappa = 0.73 (0.67-0.79) for good quality
      angiograms vs. 0.54 (0.44-0.64) for poor quality angiograms. Inter-observer
      agreement for assessment of plaque surface morphology was moderate (kappa 0.4
      0.6) and did not vary with type of angiography or method of image acquisition.
      However, ulceration was reported most frequently on selective angiograms and on
      those angiograms on which the quality of visualization of the stenosis was good.
      We conclude that the reproducibility of measurement of carotid stenosis and the
      assessment of plaque surface morphology vary depending on the type of angiography
      and the quality of visualization of the stenosis. This should be taken into
      account when validating non-invasive methods of imaging the carotid bifurcation.

PMID- 9651061
TI  - Technical report: Combined carotid bifurcation endarterectomy and intra-operative
      transluminal angioplasty of a proximal common carotid artery stenosis: an
      alternative to extrathoracic bypass.
AB  - A method of management of a dual stenoses affecting the proximal common carotid
      artery and the internal carotid artery, the tandem lesion, is described in two
      cases. The combination of a surgical endarterectomy of the internal carotid
      artery narrowing and percutaneous balloon dilatation of the more proximal common
      carotid artery narrowing, via the arteriotomy site, with clamping of the internal
      carotid artery was successfully employed to avoid an extrathoracic bypass
      procedure.

PMID- 9651062
TI  - Imaging of the portal vein during transjugular intrahepatic portosystemic shunt
      procedures: a comparison of carbon dioxide and iodinated contrast.
AB  - We report our experience with wedged hepatic injections of carbon dioxide (CO2)
      in the imaging of the portal vein during transjugular intrahepatic portosystemic
      shunt (TIPS) procedures. In all patients CO2 allowed quick and effective
      visualization of the portal vein. The image quality and extent of visualization
      of the portal vein was considered superior to iodinated contrast media in all
      cases. We suggest that CO2 should be used more frequently during TIPS.

PMID- 9651063
TI  - Gallstone ileus: CT findings.
AB  - We describe the CT findings of four consecutive cases of surgically proven
      gallstone ileus and discuss the pathophysiology of gallstone ileus and the impact
      of CT on diagnosis of the condition.

PMID- 9651064
TI  - Case report: Transcatheter embolization of a superior mesenteric artery
      pseudoaneurysm with interlocking detachable coils.

PMID- 9651065
TI  - Case report: Urinary bladder rhabdomyosarcoma associated with Beckwith-Wiedemann
      syndrome.

PMID- 9651066
TI  - Case report: Portal venous thrombosis in acute cholecystitis. CT, ultrasound,
      Doppler and power Doppler findings.

PMID- 9651067
TI  - Case report: Use of an IVC filter in the management of IVC thrombosis occurring
      as a complication of acute pancreatitis.

PMID- 9651068
TI  - Diabetics on Metformin.

PMID- 9651069
TI  - Ocular ultrasound.

PMID- 9651070
TI  - Solitary cystic nodal metastasis occult papillary carcinoma of the thyroid
      mimicking a branchial cyst--a potential pitfall.

PMID- 9651071
TI  - Corticosteroids--a case of mistaken identity?

PMID- 9651072
TI  - Skin and joint disease in psoriatic arthritis: what is the link?

PMID- 9651073
TI  - Monoclonal antibody therapy in rheumatoid arthritis.
AB  - Monoclonal antibodies bind to their targets with high specificity and therefore
      have excellent potential as therapeutic agents. Biotechnological advances have
      allowed the production of large quantities of engineered monoclonal antibodies
      for therapeutic use. Recent research in rheumatoid arthritis has identified
      important mediators of synovitis. Monoclonal antibodies targeting these have been
      tested in clinical trials over the last decade. Anti-cytokine therapies, in
      particular anti-tumour necrosis factor alpha monoclonal antibodies, suppressed
      inflammation and produced rapid symptomatic improvement. Anti-lymphocyte
      monoclonal antibodies produced long-lasting disease suppression in animal models
      of rheumatoid arthritis. The use of depleting anti-lymphocyte monoclonal
      antibodies in rheumatoid arthritis had been disappointing as they did not
      penetrate the synovial joint in sufficient quantity to suppress disease without
      producing severe and protracted peripheral blood lymphopenia. Consequently, their
      use in rheumatoid arthritis had been abandoned. In contrast, clinical trials of
      non-depleting anti-CD4 monoclonal antibodies in rheumatoid arthritis showed that
      they could suppress synovitis. However, it remains unclear whether they could
      lead to prolonged disease improvement.

PMID- 9651074
TI  - Prevalence of the major rheumatic disorders in the adult population of north
      Pakistan.
AB  - The prevalence of rheumatic diseases in developing countries is largely unknown.
      Studies which allow comparison of data within the contrasting communities of the
      Third World and the developed world have the potential to provide insights into
      disease aetiologies. The current study compared the frequency of rheumatic
      symptoms (point prevalence) amongst 1997 adults distributed evenly between poor
      rural and poor urban communities and relatively affluent urban people.
      Comparisons were also made with similarly but previously derived prevalence rates
      of rheumatic symptoms and rheumatoid arthritis (RA) in south Pakistan and
      Pakistanis in England. A significantly higher prevalence of joint pain was seen
      in the north compared with the south. RA was more common in the north and similar
      to the frequency amongst Pakistanis resident in England. Ethnic and genetic
      susceptibility might have accounted for this. There was significantly more soft
      tissue rheumatism and back pain in the northern rural population compared with
      those in the city. Fibromyalgia was almost completely absent from the urban
      affluent, but osteoarthritis of the knee was significantly more common in this
      community, perhaps due to relative obesity. RA was least in the urban poor, a
      phenomenon that might be attributable to earlier death of females or other
      undetermined factors.

PMID- 9651075
TI  - Clinical evaluation of spine morphometric X-ray absorptiometry.
AB  - A new method for vertebral height measurements, morphometric X-ray absorptiometry
      (MXA) based on dual-energy X-ray absorptiometry, has been proposed. This
      technique overcomes some limitations of morphometric radiography (MRX): the
      effective radiation dose is low, some sources of geometric distortion are
      eliminated, such as dependence on patient position, magnification gradient, and
      the effect of scoliosis is minimized. The purpose of this study was to compare
      morphometric parameters obtained by both methods (MXA and MRX), and to evaluate
      the agreement between morphometric evaluations and qualitative reading for
      vertebral fracture diagnosis. The evaluation was performed with an Hologic QDR
      2000 device in 67 women without vertebral fractures and 31 women with vertebral
      fractures (according to a qualitative assessment). The reproducibility of the
      image analysis was <4% and comparable to MRX. The estimated bias between the two
      methods was on average 10 mm, and was a function of the vertebral height,
      according to the Bland and Altman method. The agreement between MXA and other
      methods for vertebral fracture diagnosis was poor for the thoracic level above
      T7, due to a lack of resolution and rib interposition. Agreement was also low for
      T10, due to the motion of the diaphragm muscle. MXA cannot currently be used for
      the diagnosis of thoracic vertebral fracture in clinical practice. Technological
      improvements are necessary to make this promising method useful as a screening
      tool to evaluate the presence of thoracic vertebral fractures.

PMID- 9651076
TI  - Methotrexate reduces inflammatory cell numbers, expression of monokines and of
      adhesion molecules in synovial tissue of patients with rheumatoid arthritis.
AB  - Methotrexate (MTX) is one of the most widely prescribed drugs in the treatment of
      rheumatoid arthritis (RA). The mechanism by which MTX exerts its anti-rheumatic
      effect has not yet been defined. The aim of the present study was to investigate
      the effect of MTX treatment (7.5-15 mg/week) on synovial tissue in RA. For this
      purpose, synovial biopsies were taken from 11 RA patients before and 16 weeks
      after initiation of MTX therapy. Immunohistochemistry was performed using
      monoclonal antibodies (MAb) specific for CD3, CD4, CD8, CD22, CD25, CD38, CD68,
      MAb67, Ki67, interferon gamma (IFN-gamma), interleukin (IL)-1alpha, IL-1beta,
      tumour necrosis factor alpha (TNF-alpha), E-selectin, ICAM-1 and VCAM-1. All
      parameters for disease activity improved during the period of treatment.
      Immunohistochemical analysis revealed a statistically significant decrease in
      scores for CD3, CD8, CD38, CD68, Ki67, IL-1beta, TNF-alpha and the adhesion
      molecules E-selectin and VCAM-1. The observed decrease in synovial scores for
      inflammatory cells, monokines and adhesion molecules suggests that the anti
      inflammatory effect of MTX is, in part, dependent on a reduction in monokine
      inducible vascular adhesion molecules and subsequent reduction of cell traffic
      into joints.

PMID- 9651077
TI  - The short-term health outcome of out-patient rheumatology consultations in
      relation to rationing: a pilot study.
AB  - The objectives were to test whether the short-term health outcome of rheumatology
      out-patients differs according to clinical priority. The setting was an NHS
      regional rheumatology out-patient department serving a catchment population of
      over 1 million. The subjects were 249 consecutive rheumatology out-patients
      categorized on the basis of the referral letter as 'urgent' (n = 50), 'soon' (n =
      100) or 'routine' (n = 99). Primary outcome measures were the proportion of
      patients reporting improvement in health categorized by clinical priority
      (urgent, soon or routine) or main diagnostic group (inflammatory or non
      inflammatory disease). Secondary outcome was change in health status measured
      using the EuroQol generic health instrument (EQ-5D). Small but insignificant
      differences in the proportion of patients reporting health improvement were found
      between the urgent (28%), soon (23%) and routine (17%) categories (Kruskal
      Wallis, P = 0.186). Thirty per cent of patients with inflammatory joint disease
      reported improvement compared with 17% of those with non-inflammatory conditions
      (Mann-Whitney U, P = 0.019). In patients reporting improvement, the median
      (interquartile range) improvement in EQ-5D health utility score was +0.2 (0.58)
      (P = 0.0001) and that of visual analogue health score was +5 (16) (P = 0.001).
      Clinical priority setting, by giving priority to some patients over others,
      results in rationing by delay. These data do not support the hypothesis that
      fewer patients given a low clinical priority gain health benefit compared with
      those given a high priority. However, those with inflammatory joint disease do
      appear to have better short-term health outcomes.

PMID- 9651078
TI  - Body composition in systemic lupus erythematosus.
AB  - The objectives were to determine the body composition, and the effects of disease
      and corticosteroid therapy on body composition, in a population of female
      patients with systemic lupus erythematosus (SLE). All female SLE patients managed
      through a single centre were invited to participate in a cross-sectional study of
      body composition. Data were collected by standardized interview and examination,
      and review of medical records. Body composition was assessed by dual-energy X-ray
      absorptiometry (DXA). Eighty-two subjects were evaluated, 30 of whom were post
      menopausal. Univariate linear regression analysis revealed a significant
      association of reduced fat-free mass with SLE severity [as measured by the
      Systemic Lupus International Collaborative Clinics (SLICC)] (P = 0.020), a
      history of corticosteroid exposure (P = 0.043) and age (P = 0.048). Reduced total
      body bone mineral density (BMD) was also significantly associated with SLICC (P <
      0.001) and corticosteroid exposure (P = 0.017), and with age (P < 0.001), post
      menopausal status (P = 0.003) and the duration of menopause (P < 0.001). Stepwise
      multiple linear regression analysis revealed a significant association between
      fat-free mass and total body, lumbar spine and femoral neck BMD (P = 0.007, P =
      0.025, P = 0.003, respectively). Fat mass was significantly associated only with
      lumbar spine BMD (P = 0.008). In this SLE population, disease severity and
      corticosteroid exposure were independently associated with a negative effect both
      on total body BMD and on fat-free mass. Fat-free mass was a significant predictor
      of lumbar spine, femoral neck and total body BMD.

PMID- 9651079
TI  - Bacteria-specific lymphocyte proliferation in peripheral blood in reactive
      arthritis and related diseases.
AB  - The cellular immune response seems to be important for the pathogenesis of
      reactive arthritis (ReA) and a bacteria-specific lymphocyte proliferation (LP) is
      often found in synovial fluid (SF) of ReA patients. However, the role of the
      bacteria-specific LP in peripheral blood (PB) is less well defined. In this
      study, we investigated 215 paired samples of SF and PB from patients with ReA (n
      = 65), undifferentiated oligoarthritis (n = 133) and undifferentiated
      spondylarthropathy (n = 17) to analyse the LP in PB and SF in relation to time.
      In 24 out of 87 patients (27.6%) with a bacteria-specific LP in synovial fluid, a
      positive LP to the same bacterium was also found in PB. While a positive LP in SF
      was found most frequently in the first week of the arthritis, a positive LP in PB
      was detected in 45% of patients when investigated between weeks 2 and 4 after the
      onset of arthritis, but was rarely found very early and late in the course of the
      arthritis. The time point seems to be crucial for the investigation of an LP in
      PB in patients with ReA.

PMID- 9651080
TI  - Characterization of the humoral immune response to Klebsiella species in
      inflammatory bowel disease and ankylosing spondylitis.
AB  - This study was carried out to characterize the antibody class response by ELISA
      to seven Klebsiella pneumoniae serotypes (K2, K3, K17, K21, K26, K36, K50) in
      five different groups, 40 HLA-B27-positive ankylosing spondylitis (AS) patients,
      46 patients with Crohn's disease (CD), 38 patients with ulcerative colitis (UC),
      50 patients with active anti-endomysial antibody-positive coeliac disease and 40
      healthy controls, using whole bacteria and capsular polysaccharide. IgG antibody
      levels were significantly elevated in AS patients to K17, K36, K50; IgA to K2,
      K3, K21, K26, K36 and K50; and IgM to serotype K21 when compared to normal
      controls. Furthermore, IgG antibody levels were significantly elevated in CD
      patients to K2, K17, K21, K26, K36 and K50; IgA to K2, K3, K21, K26, K36 and K50;
      and IgM to K2, K3, K17, K21 and K50. Increased IgG antibody levels in the UC
      group were limited only to K17, K36 and K50. No antibody class was increased to
      any of the K. pneumoniae serotypes in the coeliac disease group. The immune
      responses in AS patients also involve Klebsiella bacteria having capsular
      serotypes other than K26, K36 and K50. The similarity in the immune responses
      between CD and AS groups suggests that many AS patients may have occult bowel
      inflammation.

PMID- 9651081
TI  - Joint stiffness and 'articular gelling': inhibition of the fusion of articular
      surfaces by surfactant.
AB  - It was proposed some years ago that, in osteoarthritis, one source of joint
      stiffness arises from 'articular gelling', but, if so, why does this not occur in
      the normal joint? In a preliminary experiment using agar gels, it is shown how
      such fusion of gel surfaces can be inhibited by surface-active phospholipid
      (SAPL)--both synthetic and human--as quantified by the shear stress needed to
      cause cleavage between samples after prolonged contact. On the other hand, normal
      bovine articular cartilage (BAC) does not fuse to itself, but can be made to do
      so if rinsed with a powerful lipid solvent known to remove the outermost layer of
      adsorbed SAPL along with the hydrophobicity so characteristic of the normal
      'waxy' surface it imparts. It is then shown how the inhibition of gel fusion can
      be restored by treating both bovine and human articular surfaces with exogenous
      SAPL derived from human AC and with synthetic SAPL. Samples of human articular
      cartilage excised from osteoarthritic hips and knees during total joint
      replacement showed a 55% greater tendency to fuse together than normal BAC. This
      was exacerbated by solvent rinsing and can be attributed to a deficiency in the
      outermost lining of SAPL previously studied as a load-bearing boundary lubricant
      capable of reducing friction and wear to the remarkably low levels observed
      physiologically. Hence, joint stiffness can be attributed, in part, to a
      deficiency in the lubricating layer of SAPL lining the normal articular surface
      where it can inhibit articular gelling/gel fusion, possibly imparting other
      desirable physiological functions. The possibility of clinical replenishment of
      SAPL in the osteoarthritic joint is discussed.

PMID- 9651082
TI  - Bone mineral density at distal forearm can identify patients with osteoporosis at
      spine or femoral neck.
AB  - Forearm bone mineral density (BMD) was investigated in women to identify
      osteoporosis at the spine or femoral neck (or both) defined by WHO criteria (T
      score -2.5) without requirement for fracture. BMD was measured by single-energy X
      ray absorptiometry (DTX100) and by dual-energy X-ray absorptiometry (DXA) in the
      lumbar spine and femoral neck in 422 subjects aged 22-90 yr. A total of 62% of
      subjects with osteoporosis (at the spine, femoral neck, or both sites) were
      detected with 89% specificity [receiver operating characteristics (ROC) analysis]
      and included all subjects below forearm BMD 0.34 g/cm2. Conversely, above 0.419
      g/cm2, only 10% of patients had osteoporosis. A total of 71.8% of women could be
      assigned either to those who warranted therapy (<0.34 g/cm2) or to those who did
      not (>0.419 g/cm2) with 90% certainty. Subjects with forearm BMD between 0.34 and
      0.419 g/cm2, who constituted 28.2% of the total group and included 31% of
      subjects with osteoporosis, had a 40% chance of having osteoporosis. This leads
      to a high identification rate on subsequent DXA scanning, which is thus used
      efficiently.

PMID- 9651083
TI  - A case of refractory adult dermatomyositis.

PMID- 9651084
TI  - The clinical management of rheumatoid arthritis and osteoarthritis: strategies
      for improving clinical effectiveness.

PMID- 9651085
TI  - National database of patients visiting rheumatologists in The Netherlands: the
      standard diagnosis register of rheumatic diseases. A report and preliminary
      analysis.

PMID- 9651086
TI  - Inflammatory cytokines and cytokine antagonists in whole blood cultures of
      patients with systemic juvenile chronic arthritis.
AB  - In the present study, we investigated the kinetics and the activation thresholds
      for the production of a number of pro-inflammatory cytokines and cytokine
      antagonists in Escherichia coli lipopolysaccharide (LPS) or phytohaemagglutinin
      (PHA) stimulated whole blood cultures of 13 patients with systemic juvenile
      chronic arthritis (SJCA) and 10 healthy children. In unstimulated cultures, the
      levels of interleukin (IL)-1beta, IL-6 and tumour necrosis factor alpha (TNF
      alpha) were undetectable in both groups, suggesting that there was no spontaneous
      production of these cytokines by circulating leucocytes. The activation
      thresholds for the production of these cytokines, as well as the capacity for
      production, did not differ significantly between patients and controls. The level
      of interleukin-1 receptor antagonist (IL-1ra) in plasma of the patients was
      significantly elevated, while the in vitro production of IL-1ra was essentially
      normal and it did not correlate with plasma levels of IL-1ra. Supernatant levels
      of soluble TNF-alpha receptor (sTNF-R) I and II were both significantly elevated
      and correlated with the global activity score. In contrast, the supernatant
      levels of IL-10 were reduced in both PHA- and LPS-driven cultures. Although IL-10
      levels did not correlate with laboratory or clinical indices of disease activity,
      the results suggest that reduced IL-10 production may play a pathogenetic role in
      SJCA.

PMID- 9651087
TI  - Increased serum IgD concentrations in children with Henoch-Schonlein purpura.
AB  - Serum IgD concentrations were measured in 39 children with Henoch Schonlein
      purpura (HSP) and 40 control children by means of radial immunodiffusion. Serum
      IgG, IgA and IgM concentrations in the HSP patients were measured by
      nephelometry. The geometric mean IgD concentration in children with HSP (16.7
      microg/ml) was significantly higher than in control children (9.1 microg/ml;
      P=0.03). Serial testing in 10 HSP patients revealed no significant change in IgD
      concentrations over periods ranging from 1 to 12 months. There was no
      relationship between IgD and IgA concentrations in the HSP patients. Nineteen of
      the 39 HSP patients (49%) had nephritis. The mean IgD concentration in patients
      with nephritis (10.7 microg/ml) did not differ from control values, but was
      significantly lower than the mean IgD level in the remaining 20 patients who did
      not have nephritis (25.4 microg/ml; P=0.02). These results indicate that serum
      IgD levels are increased in children with HSP who did not have nephritis. IgD
      concentrations in patients with nephritis were similar to levels in control
      children.

PMID- 9651088
TI  - Do psychosocial interventions have a role to play in paediatric rheumatology?

PMID- 9651089
TI  - Juvenile chronic arthritis: diagnosis and management of tibio-talar and sub-talar
      disease.

PMID- 9651090
TI  - Treatment of gout after transplantation.

PMID- 9651091
TI  - Antimalarial drugs in the treatment of rheumatological diseases.

PMID- 9651092
TI  - Kelley-Seegmiller syndrome: a case report and review of the literature.

PMID- 9651093
TI  - Sacroiliitis in an HLA B27-negative patient following giardiasis.

PMID- 9651094
TI  - Nailfold capillary microscopy in patients with Raynaud's phenomenon: experience
      in a district general hospital.

PMID- 9651095
TI  - CD134/OX40 expression by synovial fluid CD4+ T lymphocytes in chronic synovitis.

PMID- 9651096
TI  - Mseleni Joint Disease: social priorities.

PMID- 9651097
TI  - Two different drug-induced pulmonary complications in a patient suffering from
      rheumatoid arthritis.

PMID- 9651098
TI  - Trigeminal sensory neuropathy in systemic sclerosis.

PMID- 9651099
TI  - Association of antiphospholipid syndrome and chronic hepatitis C.

PMID- 9651100
TI  - Ondansetron prevents refractory and severe methotrexate-induced nausea in
      rheumatoid arthritis.

PMID- 9651101
TI  - Three infected injections from the same organism.

PMID- 9651102
TI  - Use of myoblasts in assaying the osteoinductivity of bone morphogenetic proteins.
AB  - A novel, time- and BMP-saving in vitro method for the detection and quantitation
      of bone morphogenetic protein (BMP) activity was developed based on the
      measurable effects of BMP on rat skeletal muscle myoblasts (L6). Calcium
      incorporation, stimulation of alkaline phosphatase activity and production of
      osteocalcin were used as markers of bone cell metabolism and on-going
      morphogenesis. The morphological change was confirmed by Chlorantine fast red and
      von Kossa staining. The response of various BMPs was purity-dependent and
      consistent with intramuscular implantations of the same materials. Neither TGF
      beta1 nor insulin could induce the same actions. The data from this study
      indicate that at least in part in vivo implantations of BMP extracts can be
      replaced by in vitro measurement of osteoinductivity. Considerable saving of
      time, BMP and experimental animals can be achieved using cell culture conditions
      for the determination of bone-forming activity.

PMID- 9651103
TI  - Effect of 3,5-diiodo-L-thyronine on thyroid stimulating hormone and growth
      hormone serum levels in hypothyroid rats.
AB  - We have investigated the biological effects of physiological doses of 3,5-diiodo
      L-thyronine (3,5-T2) and 3,3'-diiodo-L-thyronine (3,3'-T2) (at doses from 2.5 to
      10 microg/100 g BW) on serum TSH and GH levels in rats made hypothyroid by
      propylthiouracil and iopanoic acid administration. In such animals deiodinase
      activities were inhibited and thyroid hormones serum levels strongly reduced. The
      effects of T2s were compared with those elicited by 3,5,3'-triiodo-L-thyronine
      (T3) (2.5 microg/100 g BW).The serum TSH level was much greater in hypothyroid
      rats than in euthyroid ones. T3 administration suppressed TSH by 88% compared to
      control (i.e, the level in hypothyroid rats); it thus reached a value not
      significantly different from that seen in the euthyroid rats. 3,5-T2 produced a
      similar effect, suppressing the TSH level by about 75% compared to control; it
      thus reached values not significantly different from those of the euthyroid and
      T3-treated rats. By contrast, 3,3'-T2 had no effect on TSH, whatever the dose.
      The serum GH level was much lower in hypothyroid rats than in euthyroid ones. T3
      administration increased the GH level by about 5-fold, restoring it to the value
      seen in euthyroid rats. 3,5-T2-treated hypothyroid rats, at all the doses used
      (from 2.5 to 10 microg/100 g BW), showed increased serum GH levels: at a dose of
      10 microg/100 g BW the level reached a value about 5-fold higher than that in
      hypothyroid rats. This value was not significantly different from those of
      euthyroid and T3-treated rats. 3,3'-T2 did not affect GH levels whatever the
      dose. Thus, 3,5-T2 (but not 3,3'-T2) seems to mimic the effects of T3 on serum
      TSH and GH levels in rats.

PMID- 9651104
TI  - Pituitary adenylate cyclase-activating polypeptide (PACAP) 38 and PACAP27
      differentially stimulate growth hormone release and mRNA accumulation in porcine
      somatotropes.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) has been suggested to
      regulate growth hormone (GH) secretion in several species. Here, we analyzed the
      in vitro effects of PACAP38 and PACAP27 on the secretory activity of porcine
      somatotropes. Cultures of porcine pituitary cells were treated with PACAP38 and
      PACAP27, and GH release, intracellular GH content, and GH mRNA levels were
      evaluated. Also, the time course of changes in the somatotrope content of GH and
      its mRNA in response to PACAPs were measured. Both PACAPs stimulated GH release
      from porcine somatotropes in a broad range of doses (10(-10)-10(-6) M), yet only
      PACAP27 elicited a dose-dependent response. GH cell content remained essentially
      unchanged after PACAP treatment. In contrast, both PACAPs induced significant and
      sustained increases in GH mRNA cell content, although the response to PACAP27
      appeared faster (8 h) than to PACAP38 (16 h). These results demonstrate that
      PACAP stimulates GH production in porcine somatotropes. Furthermore, the
      differential responses induced by PACAP38 and PACAP27 suggest that distinct
      mechanisms mediate their effects on this cell type.

PMID- 9651105
TI  - Interaction of isatin with type-A natriuretic peptide receptor: possible
      mechanism.
AB  - The effect of isatin on rat brain particulate guanylate cyclase (GC) was
      investigated. The enzyme was stimulated by atrial natriuretic peptide (ANP),
      brain natriuretic peptide (BNP) and urodilatin, but not by C-type natriuretic
      peptide (CNP). Their effects were not additive, pointing to action via the GC-A
      receptor. Isatin, in dose-dependent manner, abolished this stimulation. The non
      hydrolysable ATP analogue, adenylylimidodiphosphate, potentiated the effects of
      submaximal doses of ANP, BNP and urodilatin on this particulate GC-A, and
      attenuated or abolished sensitivity to isatin. These results suggest that isatin
      antagonises the generation of second messenger by GC-A; this sensitivity might be
      regulated at an ATP binding site, possibly a protein kinase-like domain.

PMID- 9651106
TI  - The pharmacokinetic change of lidocaine by catecholamines using isolated perfused
      rat liver (IPRL).
AB  - We hypothesized that changes in the pharmacokinetics of lidocaine might reveal
      changes in portal circulation induced by catecholamines. Isolated perfused rat
      liver (IPRL) was selected as an experimental model, since experimental conditions
      in this model could be regulated. The liver was perfused with a recirculating
      system at a constant flow rate of 20 ml/min. Two milligrams of lidocaine was
      administered along with one of three drugs, dopamine, norepinephrine or adenosine
      triphosphate. The fractional transfer rate constants, k21 and k12, from medium to
      liver and liver to medium, respectively, and ke, the elimination rate constant,
      were calculated using a two-compartment model with the SAAM II program. Curves of
      decay of lidocaine from the recirculating medium consisted of a fast and a slow
      component. Norepinephrine and high-dose dopamine significantly increased k12,
      while low-dose dopamine significantly increased k21 and ke compared with control
      values. Thus, norepinephrine and high-dose dopamine increased lidocaine transfer
      rate from liver to medium, while low-dose dopamine increased the transfer rate
      from medium to liver and the rate of elimination from liver. These findings
      suggest that norepinephrine and high-dose dopamine inhibit hepatic drug uptake
      and that low-dose dopamine improves uptake in IPRL.

PMID- 9651107
TI  - Role of beta-adrenoceptor on renal interleukin-6 and tumor necrosis factor in
      spontaneously hypertensive rats.
AB  - We have shown previously in the spontaneously hypertensive rat (SHR) kidney that
      interleukin-6 (IL-6) and tumor necrosis factor (TNF) mRNA levels were low under
      conditions of acute anaesthesia and surgical stress. The reasons for the
      suppression of IL-6 and TNF gene expression in the SHR were investigated by
      examining the influence of enhanced beta-adrenergic stimulation, high blood
      pressure, and renal function (renal blood flow, glomerular filtration rate,
      plasma creatinine levels) on renal IL-6 and TNF mRNAs. The experiments were
      performed by means of the following three studies; (1) SHR and Wistar rats at 4,
      7, 9 week old were injected with lipopolysaccaride (LPS), and then a relationship
      between blood pressure levels and IL-6 and TNF mRNA levels were estimated, (2)
      isoproterenol and propranolol were administered into SHR and WKY rats, and the
      levels of IL-6 and TNF mRNA were compared, (3) under condition of anaesthesia and
      surgical stress, blood pressure and renal functions in SHR were measured, and
      then the relationships between these factors and IL-6 or TNF mRNA levels were
      analyzed. Renal IL-6 and TNF mRNAs in SHR remained low even though blood pressure
      increased with age and there was no significant correlation between IL-6 or TNF
      mRNA levels and values of blood pressure or renal function under anaesthesia and
      surgical stress. However, the inhibition of the IL-6 and TNF mRNAs in SHR was
      prevented by propranolol treatment. These results suggested that suppression of
      IL-6 and TNF mRNAs in the SHR kidney could be due to overactivity of beta
      adrenergic influences which may importantly contribute to the development of
      hypertension.

PMID- 9651108
TI  - Influence of the antidepressants desipramine and fluoxetine on tryptophan-2,3
      dioxygenase in the presence of exogenous melatonin.
AB  - The effects of desipramine and fluoxetine were examined on rat hepatic tryptophan
      2,3-dioxygenase activity in the presence or absence of exogenous melatonin. Male
      Wistar rats were treated intraperitoneally over 8 days. The antidepressants were
      also administered individually and their impact on the enzyme noted. Desipramine
      reduced basal hepatic tryptophan-2,3-dioxygenase activity in the liver while
      fluoxetine had no observable effect. However, fluoxetine also prevented the hemin
      induced elevation in total enzyme activity. Exogenous melatonin (0.25mg/kg/day)
      for 8 days counteracted the inhibitory effects of both desipramine and fluoxetine
      at concentrations of 2.5mg/kg/day. Total enzyme activity was restored when
      melatonin was administered in combination with either drug. The experimental
      findings indicate that there is chemical antagonism at the surface of the enzyme
      between melatonin and the antidepressants that abolishes the observed inhibitory
      effects of the administered compounds.

PMID- 9651109
TI  - Increased endogenous nitric oxide synthase inhibitor in patients with congestive
      heart failure.
AB  - Nitric oxide (NO) plays a role in controlling vascular tone and regulates the
      contractile properties of cardiac myocytes. Patients with heart failure exhibit
      high plasma levels of nitrite/nitrate (NOx), a stable metabolite of NO, and of
      cytokines such as tumor necrosis factor-alpha, a potent inducer of NO synthase.
      An increase in inducible NO synthase activity has been found in cardiac tissue
      from patients with dilated cardiomyopathy. These findings raise the possibility
      that local or systemic overproduction of NO induced by cytokines exerts a chronic
      negative inotropic effect on the myocardium and may have detrimental effects on
      systemic hemodynamics in patients with heart failure. Plasma levels of NG,NG
      dimethylarginine (asymmetric dimethylarginine; ADMA), a circulating endogenous NO
      synthase inhibitor, were measured in control subjects and patients with valvular,
      hypertensive, or ischemic heart diseases or idiopathic cardiomyopathy. The plasma
      levels of NOx and ADMA were assessed by high performance liquid chromatography.
      The plasma levels of NOx and ADMA were significantly elevated in patients with
      heart failure. Both NOx and ADMA were positively correlated with New York Heart
      Association functional class. There was a significant inverse correlation between
      plasma NOx and ejection fraction, as estimated by echocardiography. A significant
      relationship between plasma NOx and ADMA was found only in patients with moderate
      to severe heart failure (r=0.41, p=0.01). Findings suggest a compensatory role of
      a circulating endogenous NO synthase inhibitor against induced NO synthase
      activity in patients with heart failure.

PMID- 9651110
TI  - Delta9-tetrahydrocannabinol, but not the endogenous cannabinoid receptor ligand
      anandamide, produces conditioned place avoidance.
AB  - Although exogenous cannabinoid ligands such as delta9-tetrahydrocannabinol (THC)
      have been implicated in reward-related learning and aversion, the hedonic effects
      of the endogenous cannabinoid agonist anandamide (arachidonylethanolamide) have
      never been assessed. Thus, the effects of anandamide were tested in a place
      conditioning task. Male Wistar rats received THC (0.0-8.0 mg/kg) or anandamide
      (0.0-16.0 mg/kg) during conditioning sessions. The half-life of anandamide was
      increased by pretreatment with the protease inhibitor phenylmethylsulfonyl
      fluoride (2.0 mg/kg). A significant place aversion was found at the 1.0 and 1.5
      mg/kg doses of THC. No significant place conditioning effects were found with
      anandamide. Locomotor activity during conditioning was significantly decreased by
      the 1.0, 1.5, 2.0 and 4.0 mg/kg doses of THC as well as the 8.0 and 16.0 mg/kg
      doses of anandamide. These results fail to implicate the endogenous cannabinoid
      anandamide in reward-related learning or aversion.

PMID- 9651111
TI  - Cyclosporin A has low potency as a calcineurin inhibitor in cells expressing high
      levels of P-glycoprotein.
AB  - Cyclosporin A (CsA) is a widely-used immunosuppressant drug whose therapeutic and
      toxic actions are mediated through inhibition of calcineurin (CN), a calcium- and
      calmodulin-dependent phosphatase. Inhibition of CN by CsA requires drug binding
      to its protein cofactor in the inhibition, cyclophilin. Because cyclophilin is a
      high affinity target for CsA it is expected that this protein can act as a
      reservoir for the drug in the cell and may be able to inhibit cellular efflux of
      CsA. P-glycoprotein (P-gp) is known to increase the rate of CsA efflux from CsA
      loaded cells but it is not clear if the P-gp drug efflux pump can compete
      effectively with cyclophilin at therapeutically relevant concentrations of CsA.
      To test the hypothesis that increased expression of P-gp confers protection
      against CsA-dependent inhibition of CN phosphatase activity, KB-V cells
      expressing varying levels of P-gp were analyzed to determine the potency of CsA
      as a CN inhibitor. When intact cells were treated with CsA, a positive
      correlation was observed between P-gp expression and resistance to CsA-dependent
      inhibition of CN: the IC50 is approximately 20-fold higher in the multidrug
      resistant epidermal carcinoma cell line, KB-V, which expresses P-gp at a high
      level than in the parental, KB, cell line expressing very low levels of P-gp. The
      resistance displayed by KB-V cells is abrogated by co-administration of the P-gp
      inhibitor verapamil, whereas verapamil has no effect on CsA potency in control KB
      cells. In cell lysates from KB-V cells with different amounts of P-gp CsA
      exhibits equivalent potency, indicating that the difference in sensitivity to CsA
      among the cell types requires maintenance of cell integrity. These observations
      support the view that resistance to CN inhibition by CsA occurs in cells with
      moderately elevated P-gp activity. Therefore, P-gp activity appears to be an
      important determinant of CsA cellular specificity for both therapeutic and toxic
      effects.

PMID- 9651112
TI  - Measurement of acetylcholine released from rabbit detrusor smooth muscle using
      HPLC with electro-chemical detection coupled with microdialysis procedure.
AB  - We measured the amount of acetylcholine (ACh) released from rabbit detrusor
      smooth muscles induced by electrical field stimulation (EFS) using microdialysis
      procedure. The dialysis probe was inserted through the detrusor muscle strip and
      was continuously perfused with a Ringer solution containing physostigmine
      sulfate, at a rate of 2 microl/min. The strip was suspended in an organ bath
      filled with the modified Krebs-Henseleit solution and then EFS was delivered. The
      isometric force was recorded and monitored in each muscle preparation. The
      dialysates were collected every 10 min. ACh was determined by a high performance
      liquid chromatography with electro-chemical detection. The contraction of the
      muscle strip and ACh release induced by EFS were increased in a frequency and
      duration dependent manner. There were some differences between frequency response
      curves of contraction and frequency dependent ACh release. In the contractile
      response, the maximum contractions were observed at lower frequencies, while ACh
      releases reached the maximum at higher frequencies. There was a significant, but
      not simple correlation between EFS-induced contraction and ACh release. The
      results suggest that this new method is useful to investigate the ACh release
      from rabbit detrusor smooth muscles, and that other neurotransmitters than ACh
      possibly contribute to EFS-induced contraction.

PMID- 9651113
TI  - Pharmacological characterization of the pseudopterosins: novel anti-inflammatory
      natural products isolated from the Caribbean soft coral, Pseudopterogorgia
      elisabethae.
AB  - Pseudopterosin E (PSE), a C-10 linked fucose glycoside and pseudopterosin A
      (PSA), a C-9 xylose glycoside isolated from the marine gorgonian
      Pseudopterogorgia elisabethae were both effective in reducing PMA-induced mouse
      ear edema when administered topically (ED50 (microg/ear) PSE(38), PSA(8)) or
      systemically (ED50 (mg/kg, i.p.) PSE (14), PSA (32)). Both compounds exhibited in
      vivo analgesic activity in phenyl-p-benzoquinone-induced writhing (ED50 (mg/kg,
      i.p.) PSE(14), PSA(4). PSE inhibited zymosan-induced writhing (ED50 = 6 mg/kg,
      i.p.), with a concomitant dose-dependent inhibition of peritoneal exudate 6-keto
      prostaglandin F1alpha (ED50 = 24 mg/kg) and leukotriene C4 (ED50 = 24 mg/kg). In
      vitro, the pseudopterosins were inactive as inhibitors of phospholipase A2,
      cyclooxygenase, cytokine release, or as regulators of adhesion molecule
      expression. PSA inhibited prostaglandin E2 and leukotriene C4 production in
      zymosan-stimulated murine peritoneal macrophages (IC50 = 4 microM and 1 microM,
      respectively); however, PSE was much less effective. These data suggest that the
      pseudopterosins may mediate their anti-inflammatory effects by inhibiting
      eicosanoid release from inflammatory cells in a concentration and dose-dependent
      manner.

PMID- 9651114
TI  - Behaviour of human lymphocytic isoenzymes of 5'-nucleotidase.
AB  - The behaviour of 5'-nucleotidase isoenzymes (ecto-5'-nucleotidase, e-Ns and c-N
      II soluble 5'-nucleotidases) was studied in lymphocytes from patients with B-cell
      chronic lymphocytic leukemia. A strong reduction in ecto- and soluble activities
      was observed, although the pattern of the three 5'-nucleotidases did not always
      strictly overlap. A significant decrease (p<0.05) in ecto-5'-nucleotidase, e-Ns
      and c-N-II was found in B and T populations (B lymphocytes: 1.13, 0.88 and 1.26
      nmol/h/10(6) cells versus 95.96, 9.64 and 13.73 nmol/h/10(6) cells in controls; T
      lymphocytes: 1.31, 0.23 and 0.06 nmol/h/10(6) cells versus 9.25, 1.31 and 2.10
      nmol/h/10(6) cells in healthy subjects). The percentage of ecto-5'-nucleotidase
      positive cells (CD73+) was reduced in leukemia patients, indicating a lower
      number of active molecules on the cell surface. The results of RT-PCR analysis
      showed that the ecto-5'-nucleotidase mRNA of leukemia patients was not defective.

PMID- 9651115
TI  - Parathyroid hormone-related protein increases DNA synthesis in proximal tubule
      cells by cyclic AMP- and protein kinase C-dependent pathways.
AB  - The present study was performed to characterize the possible involvement of cAMP
      synthesis and protein kinase C (PKC) activation in the DNA synthesis-stimulating
      effect of parathyroid hormone-related protein (PTHrP) in proximal tubule cells.
      We found that DNA synthesis was stimulated by 10 microM 8BrcAMP, and 1 microM Sp
      cDBIMPS, two cAMP analogs, and also by 1 microM phorbol 12-myristate 13-acetate
      (PMA) and 100 microM 1,2-dioctanoyl-sn-glycerol, two PKC activators, and 10 nM
      [Cys23] human (h)PTHrP (24-35) amide in rabbit proximal tubule cells (PTC). Both
      Sp-cDBIMPS and PMA, at 1 microM, also increased DNA synthesis in SV40
      immortalized mouse proximal tubule cells MCT. Human PTHrP (7-34) amide [PTHrP (7
      34)] dose dependently stimulated DNA synthesis in a similar manner as
      [34Tyr]PTHrP (1-34) amide [PTHrP (1-34)], in PTC. PMA pre-treatment for 20 h,
      which downregulates PKC, completely blocked the effect induced by PTHrP (7-34),
      but not that of PTHrP (1-34), in the latter cells. In contrast, the same PMA pre
      treatment abolished the DNA synthesis stimulation by PTHrP (1-34) and PTHrP (7
      34) in MCT cells, which appear to have PTH receptors mainly coupled to
      phospholipase C and not adenylate cyclase. Our results indicate that the
      stimulatory effect of PTHrP on DNA synthesis in proximal tubule cells is mediated
      by a cAMP- and PKC-dependent mechanism.

PMID- 9651116
TI  - Polyploidization and exit from cell cycle as mechanisms of cultured melanoma cell
      resistance to methotrexate.
AB  - Numerous malignant neoplasias are found to contain varying proportions of high
      ploidy cells. Although the role they play in the tumor is poorly understood,
      several lines of evidence suggest that these cells could be especially resistant
      to various aggressions, a possibility of great interest in cancer treatment. In
      the present study, we tested this hypothesis through the analysis of the presence
      of high-ploidy cells following the administration of the chemotherapeutic agent
      methotrexate. We also determined the expression of two proliferation markers,
      PCNA and CDK1, after methotrexate-treatment. Cultured cells from the murine
      melanoma B16F10 were treated with high doses of methotrexate for seven days prior
      to determination of DNA content and proliferation markers. Our results showed an
      obvious increase in the mean ploidy of this population. Specifically, there was a
      dramatic reduction in the proportion of tetraploid cells (predominant in the
      original population), and an increase in the proportion of cells with higher
      ploidies, particularly those whose DNA content was greater than 8c, including
      some cells with ploidies greater than 16c. Furthermore, there was a reduction in
      the number of PCNA-expressing cells and the reduction was much more marked in the
      case of CDK1 that was almost absent in the modal-ploidy treated cells. These
      alterations concerning ploidy and expression of proliferation markers had
      completely reverted two weeks after withdrawal of the drug. Our results indicate
      that methotrexate at a high dosage selects a cell population heterogeneous
      concerning its ploidy level, composed of one subpopulation of high-ploidy cells
      and another of modal-ploidy cells that, considering its lack of CDK1 expression,
      would remain in a latent state to evade the effects of the drug.

PMID- 9651117
TI  - Inhibitory effects of berberine on voltage- and calcium-activated potassium
      currents in human myeloma cells.
AB  - The effects of berberine, an isoquinoline alkaloid, were investigated in human
      myeloma cells. In cells with intracellular Ca2+ concentration ([Ca2+]i) = 10 nM,
      the depolarizing square pulses from -80 mV elicited an instantaneous outward
      current with an inactivation. This outward current was voltage dependent,
      activating at -30 mV and showed inactivation with repetitive depolarization, and
      was hence believed to be n type voltage-activated K+ current (IK(V)). Berberine
      (30 microM) produced a prolongation in the recovery of IK(V) inactivation. In
      cells with [Ca2+]i = 1 microM, berberine also inhibited A23187-induced IK(Ca).
      Berberine (1-300 microM) caused the inhibition of IK(V) and IK(Ca) in the
      concentration-dependent manners. The IC50 values of berberine-induced inhibition
      of IK(V) and IK(Ca) were approximately 15 microM and 50 microM, respectively. In
      inside-out configurations, berberine inside the pipette suppressed the activity
      of K(Ca) channels without changing the single channel conductance. Berberine also
      inhibited the proliferation of this cell line and the IC50 value of berberine
      induced inhibition of cell proliferation was 5 microM. Thus, the cytotoxic effect
      of berberine in cancer cells may be partially explained by its direct blockade of
      these K+ channels.

PMID- 9651118
TI  - Involvement of dopamine D1 and D2 receptors in Fos immunoreactivity induced by
      stepholidine in both intact and denervated striatum of lesioned rats.
AB  - Stepholidine (SPD), a natural product, has been demonstrated in previous studies
      as a D1 agonist and D2 antagonist. In this work SPD-induced Fos immunoreactivity
      was examined. In the normal rats, Fos was induced in the striatum by SPD (1-20
      mg/kg, i.p.) dose-dependently. The distribution of Fos-positive cells induced by
      SPD showed a rostral-caudal decline, matching the distribution of D2 dopamine
      receptors. The Fos-positive cells were mainly found in striatal neurons
      retrogradely labeled with horseradish peroxidase (HRP) from GP but not from SN,
      and could be abolished by the pretreatment of a D2 agonist LY171555 (2 mg/kg,
      i.p.), suggesting that the Fos expression in normal rats was due to the D2
      antagonistic action of SPD. In the unilateral 6-hydroxydopamine-lesioned rats,
      SPD (4 mg/kg, i.p.) induced Fos expression in intact and denervated side of the
      striatum with different characteristics. Similar to that of normal rats, the Fos
      expression in intact side possessed the rostral-caudal gradient and could be
      abolished by the pretreatment of LY171555. However, in the denervated side, the
      Fos positive cells were widely distributed, and mainly found in striatal neurons
      retrogradely labeled from SN but not from GP. Furthermore, this expression was
      prevented by the pretreatment of SCH23390 (0.2 mg/kg, i.p.) but not LY171555,
      suggesting that the Fos expression in denervated side was due to the D1 agonistic
      action of SPD. Therefore, we concluded that the Fos expression induced by SPD in
      intact and denervated striatum was mediated via D2 and D1 receptor respectively,
      supporting the previous standpoint that SPD possesses the dual action, i.e
      antagonist to D2 and agonist to D1 receptors. Furthermore, it is suggested that
      the contralateral turning behavior induced by SPD may result from the D1-mediated
      excitation of striatonigral neurons of the denervated side of the lesioned rats.

PMID- 9651119
TI  - Characterization of bradykinin receptors in human lung fibroblasts using the
      binding of 3[H][Des-Arg10,Leu9]kallidin and [3H]NPC17731.
AB  - Bradykinin (BK) receptors are involved in pain and inflammation. Two BK receptor
      subtypes, B1 and B2, have been defined based on their pharmacological properties.
      Both B1 and B2 receptors are G-protein coupled membrane receptors. B1 receptors
      are present in smooth muscle tissue, whereas B2 receptors are found in both
      smooth muscle tissue and neurons. [Des-Arg10,Leu9]kallidin (DALKD) is a selective
      B1 receptor antagonist, and NPC17731 is a selective B2 receptor antagonist. To
      develop binding assays for the two known BK receptor subtypes, [3H]DALKD and
      [3H]NPC17731 were used as selective ligands for B1 and B2 receptors respectively.
      Both ligands bound to the CCD-16 human lung fibroblast membranes reaching
      equilibrium at 25 degrees C within 30 min. Binding was stable for at least 60
      min. The Kd of [3H]DALKD was 0.33 nM and Bmax was 52 fmol/mg membrane protein.
      The Kd of [3H]NPC17731 was 0.39 nM and Bmax was 700 fmol/mg membrane protein.
      Competition for [3H]DALKD binding with BK receptor agonists was in the order:
      [des-Arg10]KD (DAKD) > KD >> [des-Arg9]BK (DABK) > BK, and competition for
      [3H]DALKD binding with BK receptor antagonists was in the order: DALKD > [des
      Arg10]Hoe 140 (DAHoe 140) > [des-Arg9,Leu8]BK (DALBK) > NPC17731 > Hoe 140 >
      DNMFBK, suggesting that [3H]DALKD bound selectively to B1 receptors. By contrast,
      competition for [3H]NPC17731 binding by BK agonists was in the order: BK > KD >>
      DAKD > DABK, and competition for [3H]NPC17731 binding by BK antagonists was in
      the order: NPC17731 = Hoe 140 >> DNMFBK > DAHoe 140 > DALBK > DALKD, indicating
      that [3H]NPC17731 labeled B2 receptors selectively. These results demonstrate
      that [3H]DALKD and [3H]NPC17731 can be used with CCD-16 human lung fibroblast
      membranes to provide a pair of binding assays for the simultaneous evaluation of
      B1 and B2 BK receptor subtypes.

PMID- 9651120
TI  - The expressions of mRNAs for interleukin-6 (IL-6) and the IL-6 receptor (IL-6R)
      in the rat hypothalamus and midbrain during restraint stress.
AB  - Over the past few years, it has been reported that physical and psychological
      stress elevate plasma interleukin-6 (IL-6), and that neural cells can produce IL
      6 and have receptors for IL-6 (IL-6R). However, it is unknown whether IL-6 plays
      a role in regulating the functions of neural cells in response to stress. We
      demonstrated recently, using the reverse transcriptase-polymerase chain reaction
      (RT-PCR), that the levels of mRNAs for IL-6 and IL-6R in the rat brain are
      changed by restraint stress for four hours. In the present study, we investigated
      the expression of mRNAs for IL-6 and the IL-6R in the rat hypothalamus and
      midbrain during restraint stress. After rats had been restrained for 10, 30, 60,
      120 or 240 min, the hypothalamus and midbrain were removed immediately and levels
      of IL-6 mRNA and of IL-6R mRNA in these regions were determined by RT-PCR. The
      expression of mRNAs for IL-6 and IL-6R in both regions was reduced after short
      term (30-60 min) restraint stress and tended to return toward the control level
      after 120 min restraint stress. After long-term (240 min) restraint stress, the
      level of IL-6 mRNA was significantly increased in the midbrain, while the level
      of IL-6R mRNA was significantly reduced in both regions. These findings suggest
      that the need for IL-6 might decline after short-term restraint stress and,
      moreover, that the synthesis and secretion of IL-6 might be enhanced and IL-6
      might be needed as a neurotrophic factor in the midbrain after long-term stress.

PMID- 9651121
TI  - The relationship between circadian patterns of salivary cortisol and endogenous
      inhibitor of monoamine oxidase A.
AB  - The circadian pattern of free cortisol, measured in saliva, was monitored in
      normal healthy adults (N=41) for the first half hour immediately after awakening
      and in a smaller group (N=8) at timed intervals throughout the day. The
      endogenous inhibitor of monoamine oxidase A (MAO-AI) was measured in the same
      saliva samples in order to explore the relationship between circadian activation
      of the hypothalamic-pituitary-adrenocortical (HPA) axis and MAO-AI. A marked
      elevation of salivary cortisol was recorded in the first half hour immediately
      after awakening resulting in a two to three fold increase from the first
      awakening level. By contrast MAO-AI was highest immediately upon awakening and
      fell subsequently. Hence the cortisol response to awakening is preceded by
      heightened MAO-AI. Moreover those subjects who showed more persistently elevated
      MAO-AI were characterised by a more pronounced cortisol response. An association
      between MAO-AI and cortisol was also manifest in the diurnal pattern recorded at
      timed intervals throughout the day. The decline of salivary cortisol from the
      morning acrophase to the evening nadir was paralleled by MAO-AI. Both patterns of
      decline were significant (P< 0.01). Taken together with previously reported
      psychological stress studies these findings suggest a possible relationship
      between MAO-AI and HPA activity.

PMID- 9651122
TI  - Effect of chronic administration of Ginkgo biloba extract or Ginkgolide on the
      hypothalamic-pituitary-adrenal axis in the rat.
AB  - The hypersecretion of glucocorticoids during exposure to various stressors may
      induce or worsen pathological states in predisposed subjects. Therefore it is of
      interest to evaluate drugs able to reduce glucocorticoid secretion. It has
      recently been shown that chronic administration of a Ginkgo biloba extract (EGb
      761) inhibits stress-induced corticosterone hypersecretion through a reduction in
      the number of adrenal peripheral benzodiazepine receptors. The present study was
      designed to analyze the effect of EGb 761 and one of its components, Ginkgolide B
      on the biosynthesis and secretion of CRH and AVP, the hypothalamic neurohormones
      that regulate the pituitary-adrenal axis. Chronic administration of EGb 761 (50
      or 100 mg/kg p.o. daily for 14 days) reduced basal corticosterone secretion and
      the subsequent increase in CRH and AVP gene expression. Under the same
      conditions, surgically-induced increase in CRH secretion was attenuated while the
      activation of CRH gene expression, ACTH and corticosterone secretion following
      insulin-induced hypoglycemia remained unchanged. Chronic i.p. injection of
      Ginkgolide B reduced basal corticosterone secretion without alteration in the
      subsequent CRH and AVP increase. However, the stimulation of CRH gene expression
      by insulin-induced hypoglycemia was attenuated by Ginkgolide B. These data
      confirm that the administration of EGb 761 and Ginkgolide B reduces
      corticosterone secretion. In addition, these substances act also at the
      hypothalamic level and are able to reduce CRH expression and secretion. However
      the latter effect appears to be complex and may depend upon both the nature of
      stress and substance (Ginkgolide B or other compounds of EGb 761).

PMID- 9651123
TI  - The repetitive activation of extracellular signal-regulated kinase is required
      for renal regeneration in rat.
AB  - In this study, we investigated the activation of p42 extracellular signal
      regulated kinase (ERK2) during renal regeneration after HgCl2-induced acute renal
      failure (ARF) in rat. ERK2 activation was observed at 5 and 29 hr after HgCl2
      injection, respectively. The tyrosine phosphorylation of hepatocyte growth factor
      receptor (c-MET) occurred between 2.5 and 5 hr after the treatment. On the other
      hand, the phosphorylation of epidermal growth factor receptor (EGFR) was
      transiently observed at 29 hr after the injection. The peak of ornithine
      decarboxylase activity as a marker of G1 phase was at 10 hr, and subsequently the
      labeling index of proliferating cell nuclear antigen as a marker of S phase
      increased at 53 hr. These results indicate that the repetitive activation of ERK2
      related to the phosphorylation of c-MET and EGFR is required for the renal
      regeneration in HgCl2-induced ARF of rat.

PMID- 9651124
TI  - Effects of curcumin on P-glycoprotein in primary cultures of rat hepatocytes.
AB  - Curcumin is a natural phenolic compound found in the rhizomes of Curcuma longa
      and endowed with beneficial biological activities including antioxidant,
      anticarcinogenic and hepatoprotective effects. In this study curcumin was tested
      for its potential ability to interact in vitro with hepatic P-glycoprotein (Pgp),
      in a model system represented by primary cultures of rat hepatocytes, in which
      spontaneous overexpression of multidrug resistance (mdr) genes occurs. In both
      freshly-plated hepatocytes, containing low levels of Pgp, and 72 hour-cultured
      hepatocytes, containing high levels of Pgp, the Rhodamine-123 (R-123) efflux,
      which represents a specific functional test for Pgp-mediated transport, was
      inhibited by curcumin in a dose-dependent manner. Western blot analysis showed
      that 25microM curcumin, when included in the culture medium throughout the
      experimental observation (72 hours), was able to significantly lower the increase
      of mAb C219-immunoreactive protein spontaneously occurring in the cells during
      culture. Curcumin, at doses ranging from 50 to 150microM was cytotoxic for
      freshly-plated hepatocytes, as shown by the strong decrease in the cell ability
      to exclude trypan blue 24 hours later, but it was significantly less cytotoxic
      when added to 24 or 48 hour-cultured cells. The resistance to curcumin,
      progressively acquired by cells during culture, was significantly reduced by high
      concentrations of dexamethasone (DEX) or dimethyl-sulfoxide (DMSO), culture
      conditions known to inhibit the spontaneous overexpression of Pgp. In addition,
      in a concentration-dependent manner, verapamil reverted curcumin resistance in
      Pgp overexpressing hepatocytes. In photoaffinity labeling studies, curcumin
      competed with azidopine for binding to Pgp, suggesting a direct interaction with
      glycoprotein. These results suggest that curcumin is able to modulate in vitro
      both expression and function of hepatic Pgp and support the hypothesis that
      curcumin, a chemopreventive phytochemical, could reveal itself also as a compound
      endowed with chemosensitizing properties on mdr phenotype.

PMID- 9651125
TI  - Lack of cisplatin-ranitidine kinetic interactions: in vivo study in children, and
      in vitro study using dog renal brush border membrane vesicles.
AB  - The interactions between cisplatin and organic ions have been extensively
      investigated in animal models for the potential to reduce cisplatin cellular
      uptake and resultant nephrotoxicity. To further investigate the beneficial
      interaction clinically, we studied the effects of the organic cation, ranitidine,
      on the renal handling of cisplatin in children. In parallel, we examined the
      effects of cisplatin on the uptake kinetics of organic cations and anions by
      brush border membrane vesicles (BBMV) prepared from dog renal cortex. The results
      indicate that: 1) there is no measurable effect of ranitidine on renal clearance
      of cisplatin in children; and 2) BBMV uptake of anionic p-aminohippurate, but not
      cationic N-methylnicotinamide, is inhibited by cisplatin at concentrations of <1
      mM. These findings suggest that cisplatin may not share transport systems with
      organic cations to a clinically significant degree. Assuming that renal tubular
      transport is a prerequisite for cisplatin nephrotoxicity, the lack of apparent
      kinetic interactions between cisplatin and organic cations may preclude clinical
      use of organic cations as a modality to prevent cisplatin nephrotoxicity.

PMID- 9651126
TI  - Feature article: are neurons lost from the primate cerebral cortex during normal
      aging?

PMID- 9651127
TI  - Impaired performance in a conditioned reaction time task after thermocoagulatory
      lesions of the fronto-parietal cortex in rats.
AB  - The present study examined whether cortical damage in rats may disrupt the
      integrative processes and motor control involved in the performance of a reaction
      time (RT) task. To investigate the nature of the deficits in the conditioned
      task, rats were subjected, after learning, to a coagulation of pia brain surface
      of varying extent, including the frontal and parietal cortical areas. They were
      then tested daily for over one month. The behavioural task required the rats to
      hold a lever down during a variable and random delay and react quickly to the
      onset of a visual cue by releasing the lever within a RT limit for food
      reinforcement. Extensive bilateral cortical lesions had no effect on spontaneous
      motor activity, but severely impaired RT performance. Latencies to release the
      lever after the cue were dramatically increased during the first postoperative
      sessions and gradually returned to baseline levels within 3 weeks, whereas less
      dramatic but long-lasting increase in premature responding (anticipatory response
      before the visual cue) was observed throughout the testing sessions. More
      restricted lesions to the frontoparietal cortex produced a similar pattern of
      incorrect responding with a faster recovery of delayed responses and a strong
      deficit in premature responding. The major effects of lesions confined to the
      rostral pole of the frontal cortex were observed on premature responding,
      however. The present results demonstrate that the impairment in movement
      initiation is rapidly recovered within 2-3 weeks even after extensive
      thermocoagulatory lesions of the frontal and parietal areas. This recovery
      suggests the involvement of adaptive processes developing progressively and
      probably reflecting the remarkable synaptic plasticity of the extrapyramidal
      motor output. In contrast, the long-lasting increase in premature responding,
      supposed to reflect some attentional deficits, may produce anatomofunctional long
      term disorganization of subcortical structures such as the basal ganglia.
      Interestingly enough, these results show that the rat neocortex supports
      functions very similar to those of primates and provide a good model for studying
      these higher functions in operant motor procedures that require prior associative
      learning and appropriate motor coordination.

PMID- 9651128
TI  - Integrating electrophysiological and anatomical experimental data to create a
      large-scale model that simulates a delayed match-to-sample human brain imaging
      study.
AB  - We propose a model that draws together experimental evidence from anatomical,
      electrophysiological and imaging experiments in order to understand better the
      neural substrate of human imaging studies using positron electron tomography
      (PET) and functional magnetic resonance imaging (fMRI). First, we define a simple
      local circuit that reflects the major role that local connectivity plays in
      producing PET and fMRI data, which are thought to mainly reflect synaptic
      activity. Second, in order to account for the role of varying behaviors during
      the course of a typical imaging experiment, we propose a local circuit that can
      perform a delayed match-to-sample task. The elements of this circuit behave very
      much like neurons that have been found in the prefrontal cortex during similar
      tasks in monkeys. One subpopulation responds selectively only when stimuli are
      present. Two different populations show the two types of delay-period activity
      that have been identified, one with high activity both during the cue and the
      delay period, the other with a rise during the delay period only. Last, a
      subpopulation shows a brief response only if the second stimulus matches the
      first, thus mediating the decision about whether the stimuli match. We show that
      in addition to performing the task, the integrated summed synaptic activities of
      the model are similar to experimental PET data.

PMID- 9651129
TI  - Widespread origin of the primate mesofrontal dopamine system.
AB  - The dopaminergic innervation of the frontal cortex, commonly implicated in
      psychiatric and neurological disorders, has traditionally been associated with a
      circumscribed midline group of ventral tegmental area (VTA) neurons. We have
      employed a combination of retrograde tracing, using fluorescent dyes, and
      tyrosine hydroxylase (TH) immunohistochemistry to amplify knowledge of frontal
      cortex-projecting dopamine (DA) neurons in non-human primates. Injections of
      retrograde fluorochromes were made in areas 46, 8B/6M, 12, 4, 24, and the
      prelimbic (PL) and infralimbic areas (IL) of the rhesus monkey. The mesencephalic
      distribution of neurons exhibiting both retrograde labeling and TH
      immunoreactivity or retrograde labeling alone was examined from the level of the
      mammillary bodies to the locus coeruleus. DA afferents innervating the macaque
      frontal cortex as a whole originate from an unexpectedly widespread continuum of
      neurons distributed in the dorsal aspects of all three of the mesencephalic DA
      cell groups [A9, A10 and A8; generally corresponding to the DA cells of the
      substantia nigra (SN), VTA, and the retrorubral area (RRA) respectively]. A large
      number of these retrogradely labeled neurons are non-dopaminergic. The dorsal
      frontal cortex (areas 46, BB/6M and 4) receive DA projections primarily from the
      full medial-lateral extent of A9 cells dorsal to the SN pars compacta (i.e. A9
      dorsalis), the RRA and to a lesser extent from the A10 parabrachial pigmented
      nucleus (PBPG) and linear nuclei, the latter of which have been associated with
      the mesocortical DA system. In contrast, the ventromedial PL and IL exhibit a
      significantly more robust input from the PBPG and midline linear VTA nuclei than
      from the lateral groups. The anterior cingulate cortex (area 24) is innervated by
      a group of DA neurons primarily located between these laterally and medially
      concentrated populations. These findings demonstrate a degree of
      compartmentalization of the mesofrontal DA system in primates, and suggest that
      this projection should no longer be viewed as a unitary midline system.

PMID- 9651130
TI  - Behavioral constraints in the development of neuronal properties: a cortical
      model embedded in a real-world device.
AB  - The ability of organisms to categorize diverse and often novel stimuli depends on
      ongoing interactions with their environment. In a modality such as vision,
      categorization requires the generation of both selective and invariant responses
      of cortical neurons to complex visual stimuli. How does behavior contribute to
      shaping the responses of these neurons? Analysis of this question is made
      difficult by the complex multilevel interactions between many neural and
      behavioral variables. To mitigate this difficulty, we studied the development and
      ongoing plasticity of pattern-selective neuronal responses by means of synthetic
      neural modeling. For this purpose, we constructed Darwin V, which consists of a
      simulated neuronal model embedded in a real-world device that is capable of
      motion and autonomous behavior. The neuronal model consists of four major
      components: a visual system (containing cortical and subcortical networks); a
      taste system based on conductance; sets of motor neurons capable of triggering
      behavior; and a diffuse ascending (value) system. The modeled visual cortex
      consists of two areas: a topographic map responsive to elementary features
      connected to a higher-order map composed of initially non-selective neuronal
      units. During behavior over time in its environment, Darwin V encounters numerous
      objects consisting of black metal cubes displaying different patterns of white
      blobs and stripes. Initially, the lack of specific higher-order visual responses
      does not allow visual pattern discrimination, and appetitive and aversive
      behaviors are triggered by the 'taste' (surface conductivity of objects) alone.
      In the course of sensory experience, however, changes occur in visual and
      sensorimotor connection strengths, with two major consequences. First, units
      within the higher visual area acquire responses that are both pattern selective
      and translation invariant. Second, as a result of the operation of the value
      system, these responses become linked to appropriate behaviors. Analysis of
      Darwin V after such changes indicates that the continuity of self-generated
      movements is essential for the development of pattern-selective and translation
      invariant responses. The concomitant development of a preference for foveal over
      parafoveal objects was found to be due to increased behavioral interactions with
      object cubes gripped by the centrally mounted effector (snout) of Darwin V.
      Finally, even after development of higher-order visual responses, visual
      responses to more frequently encountered objects continued to be enhanced, while
      other responses were diminished. Overall, the detailed study of Darwin V over
      multiple levels of organization provides a heuristically revealing example of the
      crucial role played by behavioral and environmental interactions in the
      development of complex responses by specialized neurons.

PMID- 9651131
TI  - Direction selectivity in the middle lateral and lateral (ML and L) visual areas
      in the California ground squirrel.
AB  - Extracellular recordings obtained from the extrastriate cortex of the California
      ground squirrel, a diurnal sciurid, show that large receptive fields and a strong
      direction selectivity are present in the middle lateral area (ML) and the lateral
      area (L), located laterally to V2 and V3. Direction selectivity was tested by
      presenting stimuli of varying dimensions, shapes and speeds at different
      locations in the visual field. Most cells in ML and L (84%) were direction
      selective, with a preference for fast speeds, indicating that these areas share a
      role in motion processing. Areas ML and L may be homologous to area MT or may
      represent a case of homoplasia. A directional anisotropy for motion towards the
      vertical meridian was found in ML and L cells, suggesting that these areas may be
      involved in detecting predators and other moving objects coming from the
      periphery, rather than in processing flow fields caused by forward locomotion,
      for which a centrifugal bias might be expected.

PMID- 9651132
TI  - Gyri of the human neocortex: an MRI-based analysis of volume and variance.
AB  - This magnetic resonance imaging (MRI)-based morphometric analysis of cortical
      topography in the human brain is based upon the segmentation and parcellation of
      volumetric T1-weighted MRI data for a set of 20 young adult brains including 10
      males and 10 females. For the most part, each parcellation unit (PU) of the
      neocortex corresponds to a single or a portion of a single gyrus. The volumes of
      each PU were computed for each brain. Subsets of PUs were also grouped so as to
      represent the neocortex for the frontal, temporal, parietal and occipital lobes.
      The coefficient of variation of the mean volume of total neocortex and that of
      the neocortex assigned to individual lobes cluster around 10%, whereas that of
      neocortex assigned to the individual gyri (PU) is more than twice that value.
      Approximately 80% of the total variance in gyral volume arises from determinants
      interactive for individual and specific gyri, while only approximately 10% of the
      total variance appears to be a reflection of uniform scaling to total neocortical
      volume. Sexual dimorphism contributes a pervasive though relatively small
      component of this variance. These results have implications for the study of
      structure-function correlation, and the proper statistical methods of handling
      volumetric data in morphometric studies. In addition, the nature of the
      covariance structure of the data will lead to future hypotheses regarding the
      relationships between the various potential genetic and epigenetic gyral
      influencing factors.

PMID- 9651133
TI  - Psychological morbidity in caregivers is associated with depression in patients
      with dementia.
AB  - The relationship between psychological morbidity in caregivers and depression in
      patients with dementia was examined using data collected on 193 patient-caregiver
      dyads attending a memory disorders clinic. Caregivers had high rates and levels
      of psychological morbidity which were associated with the severity of dementia
      (but neither the type nor duration), with the caregiver being a spouse and female
      and living with the person with dementia. A logistic regression analysis
      identified clinician-rated patient depression score and demanding problem
      behaviors as being independently and significantly associated with caregiver
      psychological morbidity. This new finding of a link between patient depression
      and caregiver psychological morbidity has implications for more focused treatment
      programs for both caregivers and patients.

PMID- 9651134
TI  - Carnitine acyltransferases are not changed in Alzheimer disease.
AB  - We evaluated the activities of carnitine palmitoyltransferase (CPT), carnitine
      octanoyltransferase (COT), and carnitine acetyltransferase (CAT) in the frontal
      cortex, temporal cortex, parietal cortex, hippocampus, and cerebellum of
      Alzheimer disease (AD) patients and normal human brains. There were no
      significant differences in total CPT activity, its inhibition by malonyl-CoA, the
      effect of the detergent Triton X-100 on CPT activity, COT activity, and CAT
      activity in any of the brain regions examined whether activities were expressed
      as grams of wet weight or corrected for noncollagen protein content. The addition
      of Triton X-100 increased CAT activity by 50%. Our results suggest that there is
      no defect of fatty acid transport within the AD brain cell. Total CPT activity,
      COT activity, and CAT activity are not affected in AD nor is the ratio of CPT I
      to CPT II altered in the AD versus the normal human brain.

PMID- 9651135
TI  - Limited effect of neuritic plaques on neuronal density in the hippocampal CA1
      area of Alzheimer patients.
AB  - Neurofibrillary tangles (NFTs) and neuritic plaques (NPs) are the classic
      neuropathological hallmarks of Alzheimer disease (AD). It is generally assumed
      that the pathogenic process of AD could start by local neurotoxicity induced by
      the beta-amyloid core of plaques, followed by the appearance of NFTs and
      eventually cell death. To determine whether or not local neurotoxicity around NPs
      is indeed a major pathogenetic mechanism, we used an image analysis system to
      measure the neuronal density around Bodian-stained NPs in the hippocampal CA1
      area of eight AD patients. Neuronal density, as measured within two arbitrary
      concentric circles around NPs with a radius of 74 and 123.5 microm, respectively,
      was on average 19% and 16% lower than the density in similar control circles
      without NPs in the same section. Furthermore, neuronal density around NPs was
      inversely related to their size. To investigate the impact of such a local
      reduction in cell density around NPs on the entire CA1 area, we also determined
      the proportion of the CA1 covered by the NPs and the arbitrary concentric circles
      around them. This appeared to be 16.3% of the total CA1 area, which means that
      the negative effect of NPs on the cell density can only explain 2.6% of cell
      death in the entire CA area. In conclusion, this study suggests that although NPs
      have a local negative effect on neighboring neurons, their contribution to the
      strong decrease in CA1 cell numbers is limited.

PMID- 9651136
TI  - Silicon reduces aluminum accumulation in rats: relevance to the aluminum
      hypothesis of Alzheimer disease.
AB  - In recent years, a possible relation between the aluminum and silicon levels in
      drinking water and the risk of Alzheimer disease (AD) has been established. It
      has been suggested that silicon may have a protective effect in limiting oral
      aluminum absorption. The present study was undertaken to examine the influence of
      supplementing silicon in the diet to prevent tissue aluminum retention in rats
      exposed to oral aluminum. Three groups of adult male rats were given by gavage
      450 mg/kg/day of aluminum nitrate nonahydrate 5 days a week for 5 weeks.
      Concurrently, animals received silicon in the drinking water at 0 (positive
      control), 59, and 118 mg Si/L. A fourth group (-Al, - Si) was designated as a
      negative control group. At the end of the period of aluminum and silicon
      administration, urines were collected for 4 consecutive days, and the urinary
      aluminum levels were determined. The aluminum concentrations in the brain
      (various regions), liver, bone, spleen, and kidney were also measured. For all
      tissues, aluminum levels were significantly lower in the groups exposed to 59 and
      118 mg Si/L than in the positive control group; significant reductions in the
      urinary aluminum levels of the same groups were also found. The current results
      corroborate that silicon effectively prevents gastrointestinal aluminum
      absorption, which may be of concern in protecting against the neurotoxic effects
      of aluminum.

PMID- 9651137
TI  - Guidelines for conducting bridging studies in Alzheimer disease.
AB  - This report provides guidelines for conducting bridging studies in patients with
      Alzheimer disease (AD). Bridging studies are late phase I safety/tolerance
      studies that determine the maximum tolerated dose (MTD) in patients before phase
      II efficacy studies are initiated, facilitating the transition from phase I to
      phase II development. Determining the MTD in patients maximizes the potential to
      detect efficacy by permitting the use of the highest tolerated doses in phase II
      while providing a good understanding of potential adverse events. Bridging
      studies should be double-blind, placebo-controlled, inpatient studies conducted
      in acute-care facilities by clinical personnel who are equipped to handle
      unexpected contingencies under the oversight of a competent, multidisciplinary
      review board. Patients should be in good physical health (excluding AD), and a
      comprehensive informed consent procedure must be instituted. We recommend
      initially using a fixed-dose panel design with a dose schedule based on the MTD
      in normal volunteers and later establishing the dose titration MTD.

PMID- 9651138
TI  - Safety of tacrine: clinical trials, treatment IND, and postmarketing experience.
AB  - The safety of tacrine (Cognex), a centrally active, reversible
      acetylcholinesterase inhibitor approved in 1993 for the treatment of mild to
      moderate dementia of the Alzheimer type, was evaluated in 2,706 patients with
      Alzheimer disease (AD) in clinical trials and in 9861 patients with AD in a
      treatment investigational new drug (TIND) program. More than 190,000 patients in
      the United States received tacrine during the first 2 years following marketing
      approval. The most common tacrine-associated adverse events were elevated liver
      transaminase levels [alanine aminotransferase (ALT) and, to a lesser degree,
      aspartate aminotransferase] and peripheral cholinergic events involving primarily
      the digestive system (nausea, vomiting, diarrhea, dyspepsia, anorexia, and weight
      loss). Based on clinical trial experience, potentially clinically significant (>3
      x upper limit of normal) ALT elevations occurred in 25% of patients, requiring
      routine monitoring early in treatment. The elevations were almost always
      asymptomatic, rarely accompanied by significant increases in bilirubin, and
      related to time on drug rather than to dose (90% occurred within the first 12
      weeks of treatment). Gastrointestinal events were related to dose and generally
      of mild to moderate intensity. Tacrine-associated events, including ALT
      elevations, were reversible. Cholinergic events were manageable with dosage
      adjustment. Tacrine was not associated with permanent liver injury in clinical
      trials or a TIND setting.

PMID- 9651139
TI  - Activation of the contact system in cerebrospinal fluid of patients with
      Alzheimer disease.
AB  - Several converging lines of evidence suggest that beta-amyloid and inflammation
      may be linked in the pathogenesis of Alzheimer disease (AD), but the mechanism of
      beta-amyloid neurotoxicity is unclear. In this study, by demonstrating that high
      molecular weight kininogen may be massively cleaved in the cerebrospinal fluid
      (CSF) of patients with AD, we provide evidence of the potential involvement of
      the contact system in the inflammatory processes taking place in this disease. In
      the CSF of patients with neuroimmune inflammatory disease (multiple sclerosis,
      chronic inflammatory demyelinating polyneuropathy), there was no evidence of
      increased cleavage of high molecular weight kininogen, suggesting that this
      finding may be characteristic of the Alzheimer brain. The data obtained from in
      vitro experiments seem to indicate that the cleavage of high molecular weight
      kininogen in vivo may be the result of the interaction of beta-amyloid with
      factor XII and of kallikrein generation. The actual relevance of such a
      phenomenon remains to be established in vivo. However, the demonstration that the
      contact system may be activated in the brains of Alzheimer patients points to the
      potential involvement of the kallikrein-kinin system in the inflammatory process
      of this disease.

PMID- 9651140
TI  - Bromocriptine treatment for perseveration in demented patients.
AB  - Some forms of behavioral perseveration may reflect the disruption of specific
      neurotransmitter systems including mesencephalic dopaminergic projection. We
      present an open-labeled trial of a dopamine agonist for treating perseveration in
      dementia. Eight patients with ischemic vascular or degenerative dementia
      completed a 25-day trial of bromocriptine with a maximum daily dose of 10 mg.
      Patients were assessed with neuropsychological scales and a test battery for
      detecting perseveration. Recurrent and stuck-in-set types of perseveration
      significantly improved during the treatment, whereas measures for general
      attention and overall cognitive function showed no significant changes. We assume
      that bromocriptine supplemented the mesolimbocortical or ventral mesostriatal
      dopamine system ameliorated a certain frontal lobe function such as focused
      attention or working memory and improved the patients' perseverations. Although
      this study is preliminary because of the small sample size and open-labeled
      design, the results underline the possibility of pharmacotherapy for
      perseveration and recommend a double-blind, placebo-controlled study.

PMID- 9651141
TI  - Transcutaneous electrical nerve stimulation (TENS) improves circadian rhythm
      disturbances in Alzheimer disease.
AB  - In patients with Alzheimer disease (AD), an irregular day-night rhythm with
      behavioral restlessness during the night makes a strong demand on caregivers and
      is among the most important reasons for institutionalization. A dysfunctioning
      circadian timing system is supposed to underlie the disturbance or at least to
      contribute to it. The disturbance improves with increased environmental light,
      which, through the retinohypothalamic tract, activates the suprachiasmatic
      nucleus (SCN), the biological clock of the brain. Because recent studies have
      indicated both direct and indirect spinal projections to the SCN, we investigated
      whether excitation of spinal neurons by means of transcutaneous electrical nerve
      stimulation (TENS) could also improve circadian rhythm disturbances in AD
      patients. The actigraphically obtained rest-activity rhythm of 14 AD patients
      showed an improvement in its coupling to Zeitgeber after TENS treatment but not
      after placebo treatment.

PMID- 9651142
TI  - Three novel missense mutations in unrelated Japanese patients with type I and
      type II protein S deficiency and venous thrombosis.
AB  - A molecular analysis of protein S deficiency in three unrelated Japanese patients
      was performed. An approximately 50% reduction in both functional and immunologic
      levels of protein S was detected in the plasmas from two unrelated patients,
      designated protein S Osaka 1 and protein S Osaka 2. An approximately 50%
      reduction in the functional level, but a normal immunologic level of protein S,
      was detected in plasma from a third patient, designated protein S Osaka 3. All of
      the exons and exon/intron junctions of the protein S gene were studied using a
      strategy combining polymerase chain reaction amplification and rapid non
      radioactive single-strand conformational polymorphism analysis. We identified a G
      to-A change in exon X of the protein S gene in protein S Osaka 1. This mutation
      resulted in the substitution of Gly for Ser at position 295 in the sex hormone
      binding globulin-like region. In protein S Osaka 2, a G-to-C change at the
      position of the 3' end of exon III was identified, leading to the amino acid
      substitution of Val46 by Leu in the aromatic stack region. In protein S Osaka 3,
      an A-to-G change in exon II was identified, leading to the substitution of Lys9
      by Glu in the Gla domain. It was concluded that the Gly295-to-Ser mutation and
      Val46-to-Leu mutation cause type I protein S deficiency and that the Lys9-to-Glu
      mutation causes type II deficiency.

PMID- 9651143
TI  - Prevention of the influence of fibrin and alpha2-macroglobulin in the continuous
      measurement of the thrombin potential: implications for an endpoint determination
      of the optical density.
AB  - We proposed the endogenous thrombin potential (ETP) as an overall function test
      of the coagulation system. We recently introduced a routine test which requires
      defibrinated plasma. In order to develop an assay in which the ETP-value can be
      directly obtained by measuring the optical density, we investigated two methods
      to inhibit fibrinogen clottability and to inactivate alpha2-macroglobulin. The
      first method makes use of hydroxylamine to inactivate alpha2-macroglobulin and H
      Gly-Pro-Arg-Pro-OH to inhibit fibrin polymerization. At pH 7.35, plasma incubated
      with 25 mM hydroxylamine and 1.5 mg/mL H-Gly-Pro-Arg-Pro-OH for 5 minutes at 37
      degrees C resulted in a reduced endlevel of the amidolytic activity on small
      chromogenic substrates. The second method uses a metalloprotease purified from
      Crotalus basiliscus to remove alpha2-macroglobulin from plasma in combination
      with H-Gly-Pro-Arg-Pro-OH. Herein plasma is incubated with 3.5 LM protease during
      15 minutes at 37 degrees C in the presence of 1 mg/mL polymerization inhibitor.
      The enzymatic method results in a zero endlevel of the amidolytic activity and
      this would imply that measurement of the ETP is reduced to an endpoint
      determination of the optical density. We show that the endpoint determination of
      the optical density correlates well with the calculated ETP in plasmas with
      different degrees of anticoagulation.

PMID- 9651144
TI  - Enhancement of thrombolysis in vivo without skin and soft tissue damage by
      transcutaneous ultrasound.
AB  - Previous studies have shown that transcutaneous ultrasound enhances thrombolysis
      by streptokinase in animals in vivo; however, skin and soft tissue damage induced
      by ultrasound energy has been a major limitation. The objective of this study was
      to examine the efficacy of thrombolysis and damage to skin and soft tissues using
      a newly designed concentrated ultrasound system with a cooling manifold. Using a
      rabbit model with iliofemoral arterial thrombotic occlusions, 15 pairs of
      arteries were randomized to receive ultrasound treatment or no ultrasound
      treatment. Streptokinase (25,000 unit/kg) was given intravenously. Skin
      temperature was maintained at 25-33 degrees C when ultrasound energy was applied.
      The serum level of creatine kinase, lactate dehydrogenase, red blood cell counts,
      and platelet counts were checked at baseline, after thrombus induction, and after
      ultrasound treatment. Fifteen of fifteen (100%) iliofemoral arteries were
      angiographically recanalized after ultrasound treatment. In contrast, only 1/15
      (6.7%) contralateral arteries were patent after 1 hour. After the subsequent hour
      with heparin the patency was 14/15 in the ultrasound treated group and 3/15 in
      the control group. Histologically, the patent arteries had only minimal focal
      mural thrombus, whereas the angiographically occluded arteries had occlusive
      thrombi. There was no histologic evidence of ultrasound induced damage to
      overlying skin, soft tissues, or arteries. In addition, there was no significant
      rise of creatine kinase, lactate dehydrogenase, or decrease in red blood cell
      counts and platelet counts induced by ultrasound. In conclusion, transcutaneous
      concentrated ultrasound which significantly enhances streptokinase induced
      thrombolysis in vivo can be delivered without concomitant tissue damage. This
      simple combination therapy has clinical potential for safely treating patients
      with arterial or venous thromboses.

PMID- 9651146
TI  - Species specificity of the anticoagulant activity of human urinary soluble
      thrombomodulin.
AB  - The anticoagulant activities of human urinary soluble thrombomodulin (UTM) in
      blood taken from various species using several anticoagulant assay systems were
      compared; it was examined which coagulant assay system is appropriate for
      evaluation of the antithrombotic effects of UTM and how the species specificity
      of UTM is involved in the mechanisms of action of UTM. When anticoagulant
      activities were compared using activated partial thromboplastin time (APTT),
      thromboelastography (TEG), and thrombin generation test (TGT), the effect of UTM
      was found to be the strongest in humans among various species tested. Among the
      anticoagulant assays tested, TGT reflecting protein C (PC) activation by UTM,
      appeared to be more sensitive than APTT and TEG in detection of thrombomodulin
      activity. In the study of the mechanisms of action of UTM, UTM exhibited nearly
      the same antithrombin activity against human and rat thrombin; the rate of
      activation of human PC by thrombin/UTM complex was much higher than that of rat
      PC. Therefore, the species specificity of the anticoagulant activity of UTM may
      be attributable to thrombin/UTM-PC interaction, but not to UTM-thrombin
      interaction. From these results, we concluded that TGT reflecting PC activation
      by UTM will be a more useful assay than APTT and TEG for estimating the
      antithrombotic effects of UTM in humans. Furthermore, our findings suggest that
      UTM will exhibit more potent antithrombotic effects in humans than those in rats
      by strongly enhancing thrombin-catalyzed PC activation.

PMID- 9651145
TI  - A kinetic analysis of the interaction of human recombinant tissue factor pathway
      inhibitor with factor Xa utilizing and immunoassay and the effect of antithrombin
      III/heparin on the complex formation.
AB  - We have recently shown that a complex formation of tissue factor pathway
      inhibitor (TFPI) and factor Xa (Xa) promotes a clearance of proteoglycans
      associated TFPI. In the current studies, the interaction between human
      recombinant TFPI (h-rTFPI) and Xa were kinetically analyzed by utilizing both a
      protease inhibitor, p-(amidophenyl) methanesulfonyl fluoride hydrochloride, and a
      specific enzyme-linked immunosorbent assay for the complex of h-rTFPI with Xa. We
      further investigated the effect of antithrombin III on the complex formation
      between h-rTFPI and Xa. We found that the h-rTFPI/Xa complex formed in a time
      dependent manner: the second-order rate constant (K1) for the complex formation
      was calculated to be 0.86x10(6) M(-1)s(-1). The addition of antithrombin III to
      the h-rTFPI solution modestly reduced the rate of the complex formation between h
      rTFPI and Xa. Heparin strikingly enhanced antithrombin III's inhibition of Xa and
      resulted in complete abrogation of the complex formation between h-rTFPI and Xa
      in the absence or presence of acidic phospholipids. Furthermore, antithrombin III
      induced dissociation of the preformed h-rTFPI/Xa complex in the presence of
      heparin. These results suggest that in the presence of heparin, antithrombin III
      interferes with the catabolism of TFPI mediated via Xa.

PMID- 9651147
TI  - Cost-effectiveness of venous thrombosis prophylaxis following ischemic stroke: an
      assessment of currently available literature.

PMID- 9651148
TI  - 1-[2(R)-(2-amino-2-methylpropionylamino)-3-(1H-indol-3-yl)propionyl]- 3
      benzylpiperidine-3(S)-carboxylic acid ethyl ester (L-163,540): a potent, orally
      bioavailable, and short-duration growth hormone secretagogue.

PMID- 9651149
TI  - 5-Fluoro-2-methyl-N-[4-(5H-pyrrolo[2,1-c]-[1, 4]benzodiazepin-10(11H)-ylcarbonyl)
      3-chlorophenyl]benzamide (VPA-985): an orally active arginine vasopressin
      antagonist with selectivity for V2 receptors.

PMID- 9651150
TI  - Substituted halogenated arylsulfonamides: a new class of sigma receptor binding
      tumor imaging agents.
AB  - The discovery of a series of novel halogenated arylsulfonamides (HAS) as new
      sigma receptor binding tumor imaging agents is described. Several substituted
      halogenated sulfonamides have been prepared and characterized. Target compounds
      were examined for their affinity for sigma1 and sigma2 receptor subtypes using
      guinea pig brain membranes and rat liver membranes, respectively. A number of
      substituted halogenated sulfonamides displayed subnanomolar affinities for sigma1
      sites and low nanomolar affinities for sigma2 subtype receptors. A limited
      structure-activity relationship study of this chemical series is discussed. The
      radioiodination (I-125) of one congener member (4-[125I]iodo-N-[2-(1'
      piperidinyl)ethyl]benzenesulfonamide, 4-[125I]IPBS) was accomplished in high
      yields. The in vitro competition binding studies of 4-[125I]IPBS in guinea pig
      brain membranes with sigma receptor binding ligands confirmed its sigma
      pharmacology. The rank order of potency was BD1008 (N-[2-(3, 4
      dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine) > 4-IPBS >
      haloperidol > (+)-pentazocine > DTG (1, 3-di-o-tolylguanidine) > (-)-pentazocine.
      The inhibition constants (IC50) were 0.70, 1.46, 6.28, 10.4, 87.2, and 152 nM,
      respectively, and are consistent with labeling of sigma1 receptors. The tumor
      imaging potential of 4-[125I]IPBS was studied in C57 black mice bearing B16
      melanoma xenograft. A high tumor uptake of 4-[125I]IPBS was observed (7.40% ID/g)
      at 1 h postinjection. The wash out of activity from the tumor was slow at 6 h
      postinjection (7.22% ID/g). The tumor also had the highest amount of
      radioactivity (1.54% ID/g) at 24 h postinjection. These results demonstrate that
      radiohalogenated benzenesulfonamides could be a potentially useful class of
      compounds in nuclear oncologic scintigraphy.

PMID- 9651151
TI  - Structure-activity relationship studies of novel carbocyclic influenza
      neuraminidase inhibitors.
AB  - A series of influenza neuraminidase inhibitors with the cyclohexene scaffold
      containing lipophilic side chains have been synthesized and evaluated for
      influenza A and B neuraminidase inhibitory activity. The size and geometry of
      side chains have been modified systematically in order to investigate structure
      activity relationships of this class of compounds. The X-ray crystal structures
      of several analogues complexed with neuraminidase revealed that the lipophilic
      side chains bound to the hydrophobic pocket consisted of Glu276, Ala246, Arg224,
      and Ile222 of the enzyme active site. The structure-activity relationship studies
      of this series have also demonstrated remarkably different inhibitory potency
      between influenza A and B neuraminidase. This indicated that the lipophilic side
      chains had quite different hydrophobic interactions with influenza A and B
      neuraminidase despite their complete homology in the active site. Influenza B
      neuraminidase appeared to be much more sensitive toward the increased steric
      bulkiness of inhibitors compared to influenza A neuraminidase. From the extensive
      structure-activity relationship investigation reported in this article, GS 4071
      emerged as one of the most potent influenza neuraminidase inhibitors against both
      influenza A and B strains.

PMID- 9651152
TI  - Inhibition of human neutrophil elastase. 4. Design, synthesis, X-ray
      crystallographic analysis, and structure-activity relationships for a series of
      P2-modified, orally active peptidyl pentafluoroethyl ketones.
AB  - A series of P2-modified, orally active peptidic inhibitors of human neutrophil
      elastase (HNE) are reported. These pentafluoroethyl ketone-based inhibitors were
      designed using pentafluoroethyl ketone 1 as a model. Rational structural
      modifications were made at the P3, P2, and activating group (AG) portions of 1
      based on structure-activity relationships (SAR) developed from in vitro (measured
      Ki) data and information provided by modeling studies that docked inhibitor 1
      into the active site of HNE. The modeling-based design was corroborated with X
      ray crystallographic analysis of the complex between 1 and porcine pancreatic
      elastase (PPE) and subsequently the complex between 1 and HNE.

PMID- 9651153
TI  - New chemical descriptors relevant for the design of biologically active peptides.
      A multivariate characterization of 87 amino acids.
AB  - In this study 87 amino acids (AA.s) have been characterized by 26 physicochemical
      descriptor variables. These descriptor variables include experimentally
      determined retention values in seven thin-layer chromatography (TLC) systems,
      three nuclear magnetic resonance (NMR) shift variables, and 16 calculated
      variables, namely six semiempirical molecular orbital indices, total, polar, and
      nonpolar surface area, van der Waals volume of the side chain, log P, molecular
      weight, and four indicator variables describing hydrogen bond donor and acceptor
      properties, and side chain charge. In the present study, the data from a previous
      characterization of 55 AA.s from our laboratory have been extended with data for
      32 additional AA.s and 14 new descriptor variables. The new 32 AA.s were selected
      to represent both intermediate and more extreme physicochemical properties,
      compared to the 20 coded AA.s. The new extended and updated principal property
      scales, the z-scales, were calculated and aligned to previously reported z(old)
      scales. The appropriateness of the extended z-scales were validated by the use in
      quantitative sequence-activity modeling (QSAM) of 89 elastase substrate analogues
      and in a QSAM of 29 neurotensin analogues.

PMID- 9651154
TI  - Design of a new class of orally active fibrinogen receptor antagonists.
AB  - The integrin receptor recognition sequence Arg-Gly-Asp was successfully used as a
      template from which to develop a series of potent, selective, orally active,
      peptide-based fibrinogen receptor antagonists with a long duration of action.
      Simple modifications centered on the Arg and Gly residues quickly led to a
      modified peptide (1) with significantly enhanced ability to inhibit in vitro
      platelet aggregation. Substitution of the guanidino group in 1 by piperidine
      provided 3, which showed not only a further increase in potency but also a modest
      degree of oral efficacy. Finally, exploration of the nature of the C-terminal
      amino acid, with respect to its side-chain functionality and the carboxy
      terminus, yielded a group of molecules that showed excellent in vitro potency for
      inhibiting platelet aggregation, excellent integrin selectivity, a high level of
      oral efficacy, and an extended duration of action.

PMID- 9651155
TI  - Pharmacophores incorporating numerous excluded volumes defined by X-ray
      crystallographic structure in three-dimensional database searching: application
      to the thyroid hormone receptor.
AB  - In the present study we investigate whether augmentation of pharmacophores with
      excluded (ligand-inaccessible) volumes can condense the lengthy unspecific hit
      lists often obtained in 3D-database searching. Our pharmacophores contained
      hydrophobic features defined by the hormone, hydrogen bond donor and acceptor
      features of the liganded rat THR-alpha X-ray structure, and excluded volumes
      located at the positions and scaled according to the sizes of atoms delineating
      the binding cavity. We now show, for the first time, that it is perfectly
      feasible with the Catalyst software to search, in 1-2 h, medium-sized databases
      such as Maybridge (with 5 x 10(5) compounds registered as multiple conformers)
      with pharmacophores containing numerous (approximately 10(2)) excluded volumes.
      The excluded volumes did not slow the search significantly; for pharmacophores
      containing more features they also reduced the size of the hit list the most. For
      example, with a 7-feature pharmacophore, the Maybridge hit list shrank from 4 to
      1. The single remaining compound was subsequently shown to bind to THR-alpha with
      an IC50 of 69 microM. Thus, we conclude that structure-based pharmacophores
      augmented with numerous excluded volumes can effectively prune and focus hit
      lists. The performance of multiple excluded volume-supplemented structure-based
      pharmacophores in 3D-database mining as implemented with the Catalyst software
      compares very favorably with other published procedures, with respect to speed,
      specificity, and ease of use.

PMID- 9651156
TI  - Heteroaryl analogues of AMPA. 2. Synthesis, absolute stereochemistry,
      photochemistry, and structure-activity relationships.
AB  - We have previously shown that (S)-2-amino-3-(3-hydroxy-5-phenyl-4
      isoxazolyl)propionic acid [(S)-APPA, 2] is a weak agonist at (RS)-2-amino-3-(3
      hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptors, specifically
      activated by (S)-AMPA (1), whereas (S)-2-amino-3-[3-hydroxy-5-(2-pyridyl)-4
      isoxazolyl]propionic acid [(S)-2-Py-AMPA, 5] and (RS)-2-amino-3-[3-hydroxy-5-(2
      thiazolyl)-4-isoxazolyl]propionic acid (4) are potent AMPA agonists. On the other
      hand, (R)-APPA (3) and (R)-2-Py-AMPA (6) have been shown to be weak AMPA
      antagonists. We now report the synthesis of 2-Py-AMPA (7a) and the isomeric
      compounds 3-Py-AMPA (7b) and 4-Py-AMPA (7c) as well as the 7a analogues, (RS)-2
      amino-3-[3-hydroxy-5-(6-methyl-2-pyridyl)-4-isoxazolyl]p ropion ic acid (7d) and
      (RS)-2-amino-3-[3-hydroxy-5-(2-quinolinyl)-4-isoxazolyl]propionic acid (7e).
      Furthermore, (RS)-2-amino-3-[3-hydroxy-5-(2-furyl)-4-isoxazolyl]propionic acid (2
      Fu-AMPA, 7f) and its 5-bromo-2-furyl derivative (7g) were synthesized, and (S)-2
      Fu-AMPA (8) and (R)-2-Fu-AMPA (9) were prepared by semipreparative chiral HPLC
      resolution of 7f. HPLC analyses and circular dichroism spectroscopy indicated the
      absolute stereochemistry of 8 and 9 to be S and R, respectively. This was
      confirmed by an X-ray crystallographic analysis of 9.HCl. In receptor binding
      (IC50 values) and rat cortical wedge electrophysiological (EC50 values) studies,
      7c (IC50 = 5.5 +/- 0.6 microM; EC50 = 96 +/- 5 microM) was shown to be markedly
      weaker than 7a (IC50 = 0.57 +/- 0.16 microM; EC50 = 7.4 +/- 0.2 microM) as an
      AMPA agonist, whereas 7b,d,e were inactive. The very potent AMPA agonist effect
      of 7f (IC50 = 0.15 +/- 0.03 microM; EC50 = 1.7 +/- 0. 2 microM) was shown to
      reside exclusively in 8 (IC50 = 0.11 +/- 0.01 microM; EC50 = 0.71 +/- 0.11
      microM), whereas 9 did not interact significantly with AMPA receptors, either as
      an agonist or as an antagonist. 8 was shown to be photochemically active and is a
      potential photoaffinity label for the recognition site of the AMPA receptors.
      Compound 7g turned out to be a very weak AMPA receptor agonist (IC50 = 12 +/- 0.7
      microM; EC50 = 160 +/- 15 microM). None of these new compounds showed detectable
      effects at N-methyl-d-aspartic acid (NMDA) or kainic acid receptors in vitro. The
      present studies have emphasized that the presence of a heteroatom in the 2
      position of the heteroaryl 5-substituent greatly facilitates AMPA receptor
      agonist activity.

PMID- 9651157
TI  - Design and synthesis of m1-selective muscarinic agonists: (R)-(-)-(Z)-1
      Azabicyclo[2.2.1]heptan-3-one, O-(3-(3'-methoxyphenyl)-2-propynyl)oxime maleate
      (CI-1017), a functionally m1-selective muscarinic agonist.
AB  - The synthesis and SAR of a series of (Z)-(+/-)-1-azabicyclo[2.2. 1]heptan-3-one,
      O-(3-aryl-2-propynyl)oximes are described. The biochemistry and pharmacology of
      24Z (PD 142505) and its enantiomers are highlighted. 24Z is functionally an m1
      selective muscarinic agonist. Efficacy and m1 selectivity reside in the R
      enantiomer, (R)-24Z (CI-1017).

PMID- 9651158
TI  - Synthesis and evaluation of analogues of the partial agonist 6-(propyloxy)-4
      (methoxymethyl)-beta-carboline-3-carboxylic acid ethyl ester (6-PBC) and the full
      agonist 6-(benzyloxy)-4-(methoxymethyl)-beta-carboline-3-carboxylic acid ethyl
      ester (Zk 93423) at wild type and recombinant GABAA receptors.
AB  - A pharmacophore and an alignment rule have previously been reported for BzR
      agonist ligands. The design and synthesis of 6-(propyloxy)-4-(methoxymethyl)-beta
      carboline-3-carboxylic acid ethyl ester (6-PBC, 24, IC50 = 8.1 nM) was based on
      this pharmacophore. When evaluated in vivo this ligand exhibited
      anticonvulsant/anxiolytic activity but was devoid of the muscle relaxant/ataxic
      effects of "classical" 1,4-benzodiazepines (i.e., diazepam). Significantly, 6-PBC
      24 also reversed diazepam-induced muscle relaxation in mice. The 3-substituted
      analogues 40-46 and 48 of 6-PBC 24 and Zk 93423 27(IC50 = 1 nM) were synthesized
      and evaluated in vitro to determine what affect these modifications would have on
      the binding affinity at recombinant BzR subtypes. With the exception of the 3
      amino ligands 40 and 41, all the beta-carbolines were found to exhibit high
      binding affinity at BzR sites. The 3-propyl ether derivative 45 was also
      evaluated in vivo and found to be devoid of any proconvulsant or anticonvulsant
      activity at doses up to 40 mg/kg. The 6-(1-naphthylmethyloxy) and 6-octyloxy
      analogues 25, 26, 28, and 29 of 6-PBC 24 were synthesized to further evaluate the
      proposed alignment of agonists vs inverse agonists in the pharmacophore of the
      BzR. In addition, ligands 26 and 29 were designed to probe the dimensions of
      lipophilic pocket L3 at the agonist site. The activity of 29 was evaluated in
      vivo; however, this analogue elicited no pharmacological effects at doses up to
      80 mg/kg. These and other related beta-carbolines were also examined in five
      recombinant GABAA receptor subtypes. Ligands 52-61 all exhibited moderate to high
      affinity at GABAA receptors containing alpha1 subunits. These ligands will be
      useful in further defining the pharmacophore at alpha1 beta3 gamma2 receptors.

PMID- 9651159
TI  - Three-dimensional quantitative similarity-activity relationships (3D QSiAR) from
      SEAL similarity matrices.
AB  - The program SEAL is suited to describe the electrostatic, steric, hydrophobic,
      and hydrogen bond donor and acceptor similarity of different molecules in a
      quantitative manner. Similarity scores AF can be calculated for pairs of
      molecules, using either a certain molecular property or a sum of weighted
      properties. Alternatively, their mutual similarity can be derived from distances
      d or covariances c between SEAL-based property fields that are calculated in a
      regular grid. For a set of N chemically related molecules, such values form an N
      x N similarity matrix which can be correlated with biological activities, using
      either regression analysis and an appropriate variable selection procedure or
      partial least-squares (PLS) analysis. For the Cramer steroid data set, the test
      set predictivities (r2pred = 0.53-0.84) of different PLS models, based on a
      weighted sum of molecular properties, are superior to published results of CoMFA
      and CoMSIA studies (r2pred = 0.31-0.40), regardless of whether a common alignment
      or individual, pairwise alignments of all molecules are used in the calculation
      of the similarity matrices. Training and test set selections have a significant
      influence on the external predictivities of the models. Although the SEAL
      similarity score between two molecules is a single number, its value is based on
      the 3D properties of both molecules. The term 3D quantitative similarity-activity
      analyses (3D QSiAR) is proposed for approaches which correlate 3D structure
      derived similarity matrices with biological activities.

PMID- 9651160
TI  - Homonojirimycin isomers and N-alkylated homonojirimycins: structural and
      conformational basis of inhibition of glycosidases.
AB  - A series of natural epimers of alpha-homonojirimycin and its N-alkylated
      derivatives have been prepared to investigate the contribution of the different
      chiral centers and conformation of the specificity and potency of inhibition of
      glycosidases. These epimers and N-alkylated derivatives are alpha-homonojirimycin
      (1), beta-homonojirimycin (2), alpha-homomannojirimycin (3), beta
      homomannojirimycin (4), alpha-3,4-di-epi-homonojirimycin (5), beta-4,5-di-epi
      homonojirimycin (6), N-methyl-alpha-homonojirimycin (7), and N-butyl-alpha
      homonojirimycin (8). Compound 1 was a potent inhibitor of a range of alpha
      glucosidases with IC50 values of 1 to 0.01 microM. Compounds 2, 3, and 4 were
      surprisingly inactive as inhibitors of beta-glucosidase and alpha- and beta
      mannosidases but were moderately good as inhibitors of rice and some mammalian
      alpha-glucosidases. Compound 4 was active in the micromolar range toward all
      alpha-glucosidases tested. Furthermore, compound 4, which superimposes well on
      beta-l-fucose, was a 10-fold more effective inhibitor of alpha-l-fucosidase than
      1-deoxymannojirimycin (12) and 3, with a Ki value of 0.45 microM. Only compounds
      5 and 6 showed inhibitory activity toward alpha- and beta-galactosidases (6with
      an IC50 value of 6.4 microM against alpha-galactosidase). The high-resolution
      structure of 1 has been determined by X-ray diffraction and showed a chair
      conformation with the C1 OH (corresponding to the C6 OH in 1-deoxynojirimycin)
      predominantly equatorial to the piperidine ring in the crystal structure. This
      preferred (C1 OH equatorial) conformation was also corroborated by 1H NMR
      coupling constants. The coupling constants for 7 suggest the axial orientation of
      the C1 OH, while in 8 the C1 OH axial conformation was not observed. The C1 OH
      axial conformation appears to be responsible for more potent inhibition toward
      processing alpha-glucosidase I than alpha-glucosidase II. It has been assumed
      that the anti-HIV activity of alkaloidal glycosidase inhibitors results from the
      inhibition of processing alpha-glucosidase I, but 1, 7, and 8 were inactive
      against HIV-1 replication at 500 microg/mL as measured by inhibition of virus
      induced cytopathogenicity in MT-4 cells. In contrast, the EC50 value for N-butyl
      1-deoxynojirimycin (11), which also inhibits processing alpha-glucosidase I, was
      37 microg/mL. Compound 7 has been shown to be a better inhibitor of alpha
      glucosidase I than 1 and 8 both in vitro and in the cell culture system. These
      data imply that inhibition of HIV by glycosidase inhibitors can be due to factors
      other than simply inhibition of processing alpha-glucosidase I.

PMID- 9651161
TI  - Carbocyclic analogues of the potent cytidine deaminase inhibitor 1-(beta-D
      ribofuranosyl)-1,2-dihydropyrimidin-2-one (zebularine).
AB  - Three carbocylic analogues of the potent cytidine deaminase inhibitor (CDA)
      zebularine [1-(beta-D-ribofuranosyl)-1, 2-dihydropyrimidin-2-one, 1a] were
      synthesized. The selected pseudosugar templates correspond, respectively, to the
      cyclopentenyl moiety of neplanocin A (compound 4), the cyclopentyl moiety of
      aristeromycin (compound 5), and a newly designed, rigid bicyclo[3.1. 0]hexane
      moiety (compound 6). These three carba-nucleoside versions of zebularine were
      fashioned to overcome the inherent instability of the parent drug. Each target
      compound was approached differently using either convergent or linear approaches.
      The immediate precursor to the cyclopentenyl analogue 4 was obtained by a
      Mitsunobu coupling of pseudosugar 7 with 2-hydroxypyrimidine. The cyclopentyl
      analogue 5 was linearly constructed from carbocyclic amine 17, and the final
      target 6 was similarly constructed from the carbobicyclic amine 27. Of the three
      target compounds, only 5 showed a significant level of inhibition against human
      CDA, but it was 16 times less potent than zebularine (Ki = 38 microM vs
      Ki(apparent) = 2.3 microM). Although these carbocyclic analogues appeared to be
      more stable than zebularine, replacement of the electronegative CO4' oxygen for
      the less electronegative carbon in 4-6 presumably reduces the capacity of the
      pyrimidin-2(1H)-one ring to form a covalent hydrate, a step considered crucial
      for the compound to function as a transition-state inhibitor of the enzyme.

PMID- 9651162
TI  - Synthesis and evaluation of peptidyl Michael acceptors that inactivate human
      rhinovirus 3C protease and inhibit virus replication.
AB  - Human rhinovirus, the chief cause of the common cold, contains a positive-sense
      strand of RNA which is translated into a large polyprotein in infected cells.
      Cleavage of the latter to produce the mature viral proteins required for
      replication is catalyzed in large part by a virally encoded cysteine proteinase
      (3Cpro) which is highly selective for -Q approximately GP- cleavage sites. We
      synthesized peptidyl derivatives of vinylogous glutamine or methionine sulfone
      esters (e.g., Boc-Val-Leu-Phe-vGln-OR: R = Me, 1; R = Et, 2) and evaluated them
      as inhibitors of HRV-14 3C protease (3Cpro). Compounds 1 and 2 and several
      related tetra- and pentapeptide analogues rapidly inactivated 3Cpro with
      submicromolar IC50 values. Electrospray mass spectrometry confirmed the expected
      1:1 stoichiometry of 3Cpro inactivation by 1, 2, and several other analogues.
      Compound 2 also proved to be useful for active site titration of 3Cpro, which has
      not been possible heretofore because of the lack of a suitable reagent. In
      contrast to 1, 2, and congeners, peptidyl Michael acceptors lacking a P4 residue
      have greatly reduced or negligible activity against 3Cpro, consistent with
      previously established structure-activity relationships for 3Cpro substrates.
      Hydrolysis of the P1 vinylogous glutamine ester to a carboxylic acid also
      decreased inhibitory activity considerably, consistent with the decreased
      reactivity of acrylic acids vs acrylic esters as Michael acceptors. Incorporating
      a vinylogous methionine sulfone ester in place of the corresponding glutamine
      derivative in 1 also reduced activity substantially. Compounds 1 and 2 and
      several of their analogues inhibited HRV replication in cell culture by 50% at
      low micromolar concentrations while showing little or no evidence of cytotoxicity
      at 10-fold higher concentrations. Peptidyl Michael acceptors and their analogues
      may prove useful as therapeutic agents for pathologies involving cysteine
      proteinase enzymes.

PMID- 9651163
TI  - Synthesis and biological evaluations of 3-substituted indolin-2-ones: a novel
      class of tyrosine kinase inhibitors that exhibit selectivity toward particular
      receptor tyrosine kinases.
AB  - 3-Substituted indolin-2-ones have been designed and synthesized as a novel class
      of tyrosine kinase inhibitors which exhibit selectivity toward different receptor
      tyrosine kinases (RTKs). These compounds have been evaluated for their relative
      inhibitory properties against a panel of RTKs in intact cells. By modifying the 3
      substituted indolin-2-ones, we have identified compounds which showed selective
      inhibition of the ligand-dependent autophosphorylation of various RTKs at
      submicromolar levels in cells. Structure-activity analysis for these compounds
      and their relative potency and selectivity to inhibit particular RTKs has
      determined that (1) 3-[(five-membered heteroaryl ring)methylidenyl]indolin-2-ones
      are highly specific against the VEGF (Flk-1) RTK activity, (2) 3-(substituted
      benzylidenyl)indolin-2-ones containing bulky group(s) in the phenyl ring at the C
      3 position of indolin-2-ones showed high selectivity toward the EGF and Her-2
      RTKs, and (3) the compound containing an extended side chain at the C-3 position
      of the indolin-2-one (16) exhibited high potency and selectivity when tested
      against the PDGF and VEGF (Flk-1) RTKs. Recent published crystallographic data
      for two of these 3-substituted indolin-2-ones provides a rationale to suggest
      that these compounds may bind in the ATP binding pocket of RTKs. The structure
      activity analysis supports the use of subsets of these compounds as specific
      chemical leads for the development of RTK-specific drugs with broad application
      for the treatment of human diseases.

PMID- 9651164
TI  - Neurosteroid analogues. 6. The synthesis and GABAA receptor pharmacology of
      enantiomers of dehydroepiandrosterone sulfate, pregnenolone sulfate, and
      (3alpha,5beta)-3-hydroxypregnan-20-one sulfate.
AB  - The unnatural enantiomers of dehydroepiandrosterone sulfate (1), pregnenolone
      sulfate (2), and (3alpha,5beta)-3-hydroxypregnan-20-one sulfate (3), compounds 4
      6, respectively, were prepared by total steroid synthesis. The enantioselectivity
      of the compounds as negative modulators of the GABAA receptors present in
      cultured rat hippocampal neurons was examined using electrophysiological methods.
      Enantioselectivity was found for the inhibitory actions of the
      dehydroepiandrosterone enantiomers. The IC50s for compounds 1 and 4 were 11 +/- 1
      and 80 +/- 14 microM, respectively. Little, if any, enantioselectivity was found
      for the other two pairs of steroid sulfate inhibitors. The IC50s for compounds 2
      and 5 were 82 +/- 12 and 76 +/- 27 microM, respectively. The IC50s for compounds
      3 and 6 were 39 +/- 7 and 46 +/- 2 microM, respectively. The results suggest that
      the sites of action for the androstane and pregnane series of steroid sulfate
      blockers of GABA-mediated current are different. The observed enantioselectivity
      for the actions of dehydroepiandrosterone sulfate indicates that its inhibitory
      actions are mediated via a chiral recognition site and provides new evidence in
      support of the earlier hypothesis that there is a binding site for this compound
      on GABAA receptors. Conversely, the failure to observe enantioselectivity for the
      actions of pregnenolone sulfate and steroid sulfate 3 indicates that a chiral
      recognition site for these steroids does not exist on GABAA receptors and
      suggests that the effects of these compounds on this receptor's function may
      arise indirectly as a consequence of steroid-induced membrane perturbation.

PMID- 9651165
TI  - Minimal-size, constrained corticotropin-releasing factor agonists with i-(i+3)
      Glu-Lys and Lys-Glu bridges.
AB  - In three earlier publications (Miranda et al. J. Med. Chem. 1994, 37, 1450-1459;
      1997, 40, 3651-3658; Gulyas et al. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 10575
      10579) we have hypothesized that covalent constraints such as side-chain-to-side
      chain lactam rings would stabilize an alpha-helical conformation shown to be
      important for the recognition and binding of the CRF C-terminus 30 residues, to
      CRF receptors. These studies led to the discovery of useful CRF antagonists such
      as alpha-helical CRF (alpha-hel-CRF) and Astressin both in vitro and in vivo. To
      test the hypothesis that such lactam rings may also be modulating activation of
      the receptor when introduced at the N-terminus of CRF, we studied the influence
      of the successive introduction from residues 4 to 14 of a cyclo(i, i+3)[Lysi
      Glu(i+3)] and a cyclo(i,i+3)[Glui-Lys(i+3)] bridge on the in vitro potency of the
      agonist [Ac-Pro4,dPhe12,Nle21,38]hCRF(4-41) and related compounds. We have also
      introduced the favored cyclo(Glu30-Lys33) substitution found to be remarkable in
      several families of antagonists (such as Astressin) and in a number of CRF
      agonists and investigated the role of residues 4-8 on receptor activation using
      successive deletions. Earlier studies had shown that in both oCRF and alpha
      helical CRF, deletion of residues 1-6, 1-7, and 1-8 led to gradual loss of
      intrinsic activity (IA) (from 50% IA to <10% IA) resulting in alpha-hel-CRF being
      a potent competitive antagonist. We show that acetylation of the N-terminus of
      these fragments generally increases potency by a factor of 2-3 with no influence
      on IA. While cyclo(30-33)[Ac-Leu8,dPhe12,Nle21, Glu30,Lys33,Nle38]hCRF(8-41) (30)
      is the shortest reported analogue of CRF to be equipotent to CRF (70% IA), the
      corresponding linear analogue (31) is 120 times less potent (59% IA). Addition of
      one amino acid at the N-terminus ?cyclo(30-33)[Ac-Ser7,dPhe12,Nle21,
      Glu30,Lys33,Nle38]hCRF(7-41) (28)? results in a 5-fold increase in agonist
      potency and full intrinsic activity (113%). The most favored modifications were
      also introduced in other members of the CRF family including sauvagine (Sau),
      urotensin (Utn), urocortin (Ucn), and alpha-hel-CRF. Parallel and consistent
      results were obtained suggesting that the lactam cyclization at residues 29-32
      and 30-33 (for the members of the CRF family with 40 and 41 amino acid residues,
      respectively) will induce (in the shortened agonists) a structural constraint
      (alpha-helix) that stabilizes a bioactive conformation similar to that shown in
      the Astressin family of CRF antagonists and that residue 8 (leucine or
      isoleucine) bears the sole responsibility for activation of the receptor since
      deletion of that residue leads to potent antagonists (Gulyas et al. Proc. Natl.
      Acad.Sci. U.S.A. 1995, 92, 10575-10579).

PMID- 9651166
TI  - Synthesis of 7,8-(methylenedioxy)-1-phenyl-3,5-dihydro-4H-2, 3-benzodiazepin-4
      ones as novel and potent noncompetitive AMPA receptor antagonists.
AB  - A group of 7,8-(methylenedioxy)-1-phenyl-3,5-dihydro-4H-2, 3-benzodiazepin-4-ones
      was synthesized and assayed for antagonism of rat brain alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionic acid (AMPA) receptors expressed in Xenopus oocytes.
      The benzodiazepinones inhibited AMPA-activated membrane current responses in a
      manner consistent with noncompetitive, allosteric inhibition of the receptor
      channel complex. The most potent compound in the series was 1-(4-aminophenyl)-7,8
      (methylenedioxy)-3,5-dihydro-4H-2, 3-benzodiazepin-4-one (6), which had an IC50
      of 2.7 microM. For comparison, the reference compound GYKI 52466 (2) had an IC50
      of 6.9 microM. Compound 6 also had potent anticonvulsant activity in a mouse
      maximum electroshock-induced seizure (MES) assay: the ED50 was 2.8 mg/kg iv,
      whereas the ED50 for GYKI 52466 was 4.6 mg/kg iv. In contrast to a previous
      report, the 7,8-dimethoxy analogue of 6 was a low-potency AMPA antagonist (IC50
      >100 microM) and weak anticonvulsant (ED50 >10 mg/kg iv). The benzodiazepinones
      described herein are potent noncompetitive AMPA receptor antagonists that could
      have therapeutic potential as anticonvulsants and neuroprotectants.

PMID- 9651167
TI  - In vitro platelet-activating factor receptor binding inhibitory activity of
      pinusolide derivatives: a structure-activity study.
AB  - Pinusolide, a labdane-type diterpene lactone isolated from Biota orientalis, was
      found to be a potent platelet-activating factor (PAF) receptor binding
      antagonist. To investigate the structure-activity relationship and find
      derivatives with improved pharmacological profiles, 17 pinusolide derivatives
      were prepared and tested for their ability to inhibit the PAF receptor binding.
      The results demonstrated that the carboxymethyl ester group at C-19, the
      integrity of the alpha,beta-unsaturated butenolide ring, and the exocyclic
      olefinic function of pinusolide are all necessary for its maximum PAF receptor
      binding inhibitory activity. Among the derivatives, the 17-nor-8-oxo derivative 8
      was found to be as potent as pinusolide. The results also suggested that several
      derivatives warrant further pharmaceutical and pharmacological studies due to
      their improved water solubility (8 and 11) and apparent lack of susceptibility to
      Michael-type nucleophilic addition (13 and 18).

PMID- 9651169
TI  - Nitroaromatic amino acids as inhibitors of neuronal nitric oxide synthase.
AB  - Nitric oxide (NO.) is an important biomodulator of many physiological processes.
      The inhibition of inappropriate production of NO. by the isoforms of nitric oxide
      synthase (NOS) has been proposed as a therapeutic approach for the treatment of
      stroke, inflammation, and other processes. In this study, certain 2-nitroaryl
      substituted amino acid analogues were discovered to inhibit NOS. Analogues
      bearing a 5-methyl substituent on the aromatic ring demonstrated maximal
      inhibitory potency. For two selected inhibitors, investigation of the kinetics of
      the enzyme showed the inhibition to be competitive with l-arginine. Additionally,
      functional NOS inhibition in tissue preparations was demonstrated.

PMID- 9651168
TI  - Synthesis and biological activity of a novel methylamine-bridged enkephalin
      analogue (MABE): a new route to cyclic peptides and peptidomimetics.
AB  - The synthesis and biological activity of a methylamine-bridged enkephalin
      analogue (MABE) is presented. The key step in the synthesis of the target
      compound involves the ring opening of Cbz-d-serine beta-lactone with Boc-Phe
      NHCH2CH2NHCH3. Further synthetic elaboration of the resulting building block
      yielded compound 1 (MABE, Tyr-c[(NbetaCH3)-D-A2pr-Gly-Phe-NHCH2CH2-], where A2pr
      is a 2,3-diaminopropionic acid residue). Utilizing a combination of NMR and
      molecular modeling, the structure-biological activity relationships for compound
      1 were studied. Using an in vitro isolated receptor assay, MABE was found to have
      affinities for isolated mu delta, and kappa opioid receptors of 1.6, 2.1, and 340
      nM, respectively. By an in vivo thermal escape assay, MABE was found to have an
      ED50 of 0.027 microg in the rat when administered intrathecally. This effect was
      reversed by naloxone. By comparison, DAMGO, morphine, and DPDPE were found to
      yield ED50 values of 0.14, 2.4, and 54 microg, respectively, in the same assay.

PMID- 9651170
TI  - Identification of a dihydropyridine as a potent alpha1a adrenoceptor-selective
      antagonist that inhibits phenylephrine-induced contraction of the human prostate.
AB  - A number of novel dihydropyridine derivatives based upon 1, 4-dihydro-3
      (methoxycarbonyl)-2, 6-dimethyl-4-(4-nitrophenyl)-5-((3-(4, 4-diphenylpiperidin-1
      yl)propyl)aminocarbonyl)pyridine (4) have been synthesized and tested at cloned
      human alpha adrenoceptors as well as the rat L-type calcium channel. Within this
      compound series, 5-(aminocarbonyl)-1,4-dihydro-2, 6-dimethyl-4-(4-nitrophenyl)-3
      ((3-(4, 4-diphenylpiperidin-1-yl)propyl)aminocarbonyl)pyridine (19) displayed
      good binding affinity and selectivity for the alpha1a adrenoceptor (pKi = 8.73)
      and potently inhibited (pA2 = 9.23) phenylephrine-induced contraction of the
      human prostate.

PMID- 9651171
TI  - N-Arylalkyl pseudopeptide inhibitors of farnesyltransferase.
AB  - Inhibitors of Ras protein farnesyltransferase are described which are reduced
      pseudopeptides related to the C-terminal tetrapeptide of the Ras protein that
      signals farnesylation. Reduction of the carbonyl groups linking the first three
      residues of the tetrapeptide leads to active inhibitors which are chemically
      unstable. Stability can be restored by alkylating the central amine of the
      tetrapeptide. Studies of the SAR of these alkylated pseudopeptides with
      concomitant modification of the side chain of the third residue led to 2(S)-(2(S)
      ?[2(S)-(2(R)-amino-3-mercaptopropylamino)-3(S)- methylpentyl]naphthalen-1
      ylmethylamino?acetylamino)-4 -methylsulfany lbutyric acid (11), a subnanomolar
      inhibitor. The methyl ester (10) of this compound exhibited submicromolar
      activity in the processing assay and selectively inhibited anchorage-independent
      growth of Rat1 cells transformed by v-ras at 2.5-5 microM.

PMID- 9651173
TI  - Matching scientific with societal interests: charges for the new editor.

PMID- 9651172
TI  - 14-Desoxy analogues of naltrindole and 7-spiroindanyloxymorphone: the role of the
      14-hydroxy group at delta opioid receptors.
AB  - The 14-hydroxy group is known to increase the antagonist potency of mu-selective
      opioid ligands. To investigate the role of this group at the delta opioid
      receptor, the 14-desoxy analogues (7 and 9) of the delta-selective ligands,
      naltrindole (1, NTI) and spiroindanyloxymorphone (2, SIOM), have been synthesized
      and tested. The in vitro pharmacologic activities of 7 and 9 suggest that the 14
      hydroxy group plays an important role in determining the delta selectivity and
      potency of NTI and SIOM.

PMID- 9651174
TI  - Assessment of activation, differentiation, and carcinogenesis of lung cells by
      quantitative competitive RT-PCR.

PMID- 9651175
TI  - Expression measurement of many genes simultaneously by quantitative RT-PCR using
      standardized mixtures of competitive templates.
AB  - Progress toward complete sequencing of all human genes through the Human Genome
      Project has already resulted in a need for methods that allow quantitative
      expression measurement of multiple genes simultaneously. It is increasingly
      recognized that relative measurement of multiple genes will provide more
      mechanistic information regarding cell pathophysiology than measurement of
      individual genes one by one or by methods that do not allow direct intergene
      comparison. In this study, previously described quantitative reverse
      transcription-polymerase chain reaction methods were modified in an effort to
      provide a rapid, simple method for this purpose. Internal standard competitive
      templates (CTs) were prepared for each gene and were combined in a single
      solution containing CTs for more than 40 genes at defined concentrations relative
      to one another. Any subsequent dilution of the CT mixture did not alter the
      relationship of one CT to another. Because the same CT standard solution or a
      dilution of it was used in all experiments, data obtained from different
      experiments were easily compared. The use of multiple CT mixtures with different
      housekeeping gene to target gene ratios provided a linear dynamic range spanning
      the range of expression of all genes thus far evaluated. CT stock solutions were
      used to simultaneously quantify the expression of 25 genes relative to beta-actin
      and glyceraldehyde-3-phosphate dehydrogenase in normal and malignant bronchial
      epithelial cells. Because the CT concentrations were known, data in the form of
      both absolute messenger RNA (mRNA) copy number and mRNA relative to housekeeping
      gene mRNA were obtained. The methods and reagents described will allow rapid,
      quantitative measurement of multiple genes simultaneously, using inexpensive and
      widely available equipment. Furthermore, the CT standard solution may be
      distributed to other investigators for interlaboratory standardization of
      experimental conditions.

PMID- 9651176
TI  - The gene expression index c-myc x E2F-1/p21 is highly predictive of malignant
      phenotype in human bronchial epithelial cells.
AB  - Recent methodological developments allow expression measurement of many genes
      simultaneously, thereby revealing patterns of gene expression that can be related
      to phenotype. We hypothesized that through the use of such methods we could
      identify patterns of gene expression associated with the malignant phenotype in
      human bronchial epithelial cells (BEC). To test this hypothesis, a recently
      developed quantitative reverse transcriptase polymerase chain reaction method was
      used to assess simultaneously expression of 15 genes mechanistically associated
      with cell-cycle control (c-myc, E2F-1, p21, rb, PCNA, cyclin D2, cyclin D3,
      cyclin E, cdc2, CDK2, CDK4, mad, max p21, max p22, and p53) in normal cell
      cultures from five individuals and in nine different malignant BEC lines.
      Relative to the mean expression levels in cultured normal cell populations,
      expression of c-myc, E2F-1, PCNA, cyclin E, and CDK4 messenger RNA (mRNA) were
      significantly increased and expression of p21 and p53 mRNA were significantly
      decreased in one or two, but not all three subtypes (squamous, adenocarcinoma and
      small cell) of carcinoma cell lines evaluated. No single cell-cycle control gene
      discriminated all three subtypes from normal cell populations. In contrast, the
      gene expression index c-myc x E2F-1/p21 separated all carcinoma cell lines from
      all normal cell populations initially evaluated. This malignancy index was
      validated in an additional three cultured normal BEC and three carcinoma cell
      lines, as well as three pairs of matched primary normal bronchial epithelial and
      primary bronchogenic carcinoma samples, and three pairs of matched primary normal
      lung parenchyma and primary bronchogenic carcinoma tissue. Again, the c-myc x E2F
      1/ p21 index successfully discriminated all cultured and primary normal from
      malignant samples and thereby had a predictive value of 1 (no false positives and
      no false negatives). We hypothesize that because of functional mutations in cell
      cycle regulatory genes (e.g., p53 and/or rb), cells lose the ability to maintain
      a pattern of gene expression mechanistically associated with normal, division
      limited homeostatic equilibrium. Because the c-myc x E2F-1/p21 gene expression
      index has high specificity for malignant tissue, it will allow confirmation that
      there is a significant amount of tumor tissue present in small (e.g., fine
      needle) biopsy specimens prior to evaluating them for expression of other genes,
      such as those involved in chemoresistance or radioresistance. In addition, the
      goal of most gene therapy efforts is to alter levels of gene expression
      quantitatively. This index and others derived in a similar manner may better
      define potential gene therapy targets as well as response of targeted genes to
      therapy.

PMID- 9651177
TI  - Loss of spr1 expression measurable by quantitative RT-PCR in human bronchogenic
      carcinoma cell lines.
AB  - Expression of the small, proline-rich protein (spr1) squamous differentiation
      marker was measured in five cultured normal and 12 malignant human bronchial
      epithelial cell (BEC) populations by quantitative reverse transcriptase
      polymerase chain reaction (RT-PCR). Whereas spr1 expression was quantifiable and
      inducible in all five cultured normal cell populations, in all 12 carcinoma cell
      lines evaluated it was neither quantifiable nor inducible. Primers spanning the
      entire spr1 coding sequence amplified full-length PCR product from genomic DNA;
      therefore, large deletions in the coding region were not responsible for the loss
      of expression measurable by RT-PCR. This is the first molecular genetic marker
      reported that distinguishes all normal from all carcinoma cell populations
      evaluated. Because the spr1 protein is a component of the crosslinked envelope
      that forms during the squamous differentiation process, we hypothesize that the
      apparent loss of spr1 gene expression disrupts mechanisms for terminal squamous
      differentiation in the bronchial epithelium, thereby contributing to malignant
      transformation.

PMID- 9651178
TI  - MUC5B and MUC7 are differentially expressed in mucous and serous cells of
      submucosal glands in human bronchial airways.
AB  - Mucins are high molecular-weight glycoproteins involved in the protection and
      lubrication of respiratory, gastrointestinal, and reproductive tracts.
      Hypersecretory diseases such as cystic fibrosis (CF), chronic bronchitis, and
      asthma result in dysregulated levels of mucin production stemming from increased
      abundance of mucin-secreting cell types in the surface airway epithelium and
      submucosal glands. The isolation of at least nine mucin genes has prompted
      studies to characterize the cellular expression patterns of these mucins in
      normal and diseased tissues. In the present study, in situ hybridization and
      immunocytochemical methods were used to determine the cellular distribution of
      MUC5B and MUC7 expression in CF and non-CF human bronchus. Our findings indicate
      that MUC5B and MUC7 have expression patterns in human bronchial airways that are
      limited exclusively to submucosal glands. Specifically, MUC5B expression was
      confined to all mucous tubules, whereas MUC7 expression was seen in a subset of
      lysozyme expressing serous tubules of submucosal glands. Interestingly,
      heterogeneity of MUC7 expression between glands of the same bronchus ranged from
      0 to 93% of serous tubules, suggesting that functional diversity may exist
      between glands within the same bronchial sample. No remarkable differences were
      observed in the expression patterns of MUC5B or MUC7 between CF (n = 7) and non
      CF (n = 10) bronchial samples. In conclusion, MUC5B and MUC7 expressions define
      different cellular compartments within submucosal glands of human bronchus and
      lend insight into the heterogeneity of mucin production in the lung.

PMID- 9651179
TI  - Induction, duration, and resolution of airway goblet cell hyperplasia in a murine
      model of atopic asthma: effect of concurrent infection with respiratory syncytial
      virus and response to dexamethasone.
AB  - We recently described a murine model of atopic asthma in which a marked,
      extensive hyperplasia of airway goblet cells is induced by repeated challenge of
      ovalbumin (OA)-sensitized mice with intratracheally administered allergen (Am. J.
      Respir. Cell Mol. Biol. 1996;14:425-438). We report here the time course of the
      duration of this feature and of its spontaneous resolution in the absence of
      further allergen exposure. Induction of severe neutrophilic inflammation in the
      airways by repeated intratracheal administration of lipopolysaccharide failed to
      induce goblet cell hyperplasia (GCH) to as great a degree as that induced by
      allergen, suggesting that nonallergic inflammation is a relatively poor inducer
      of this phenotype change in mice. When a "subclinical" infection of the lungs
      with the human A2 strain of respiratory syncytial virus was superimposed on the
      model of atopic asthma, recruitment of monocytes and lymphocytes to the airways
      was enhanced and a discharge of goblet cell mucin contents was observed. This may
      partly explain the respiratory difficulty that typifies virally induced
      exacerbations of asthma in humans. Daily systemic treatment of sensitized mice
      with dexamethasone during the period of allergen challenge produced a dose
      related suppression of developing GCH, while similar treatment during the period
      following the establishment of extensive hyperplasia induced an accelerated
      resolution toward a normal epithelial phenotype. These results confirm and extend
      the relevance of this model as a representation of the human disease.

PMID- 9651180
TI  - Enhanced expression of GM-CSF in differentiating eosinophils of atopic and atopic
      asthmatic subjects.
AB  - Higher numbers of eosinophil/basophil colony-forming units (Eo/B CFU) are
      observed in blood of atopic individuals, and can be enhanced in atopic asthmatics
      by allergen-inhalation challenge. It is known that mature basophils and
      eosinophils synthesize cytokines relevant to allergic inflammation. To
      investigate the potential role of growth factors in allergic disease we examined
      the expression of the hemopoietic cytokines, granulocyte-macrophage colony
      stimulating factor (GM-CSF) and interleukin (IL)-5, in differentiating Eo/B
      colony cells from normal and atopic individuals, and from atopic asthmatics
      before and after allergen-inhalation challenge. Peripheral blood was collected
      from two normal and 12 atopic individuals, and also from 25 atopic asthmatics
      before and 24 h after allergen challenge. Nonadherent mononuclear cells were
      isolated and grown in semisolid growth medium. Eo/B colonies were selected and
      cytospins were prepared for immunocytochemical analysis of colony cells. Eo/B
      colonies, especially carbol chromotrope 2R+ cells, selected at Days 10, 14, and
      18 from atopic donors contained messenger RNA for GM-CSF by combined in situ
      reverse transcription-polymerase chain reaction and cytochemistry, and
      demonstrated time-dependent expression of GM-CSF by immunocytochemistry (P =
      0.007). Atopic individuals demonstrated a higher percentage of cells expressing
      GM-CSF than did normal subjects under all growth conditions when examined at Day
      14 (P = 0. 04). Atopic asthmatics challenged with inhaled allergen who
      demonstrated a dual airway response, an increase in the number of blood
      eosinophils (P = 0.0001), and an increase in the number of Eo/B CFU (P = 0.02)
      also demonstrated a significant increase in the percentage of colony cells
      expressing immunostainable GM-CSF (P = 0. 0009), but only a variable effect on
      those expressing IL-5, 24 h after allergen. These results suggest that GM-CSF
      expression by differentiating Eo/Bs may provide an additional stimulus in vivo to
      enhance Eo/B progenitor differentiation in atopic and asthmatic individuals,
      especially after allergen challenge. The concept of microenvironmental
      differentiation, where blood progenitor cells may aid in their own
      differentiation, is supported by these ex vivo findings.

PMID- 9651181
TI  - Modulation of glucose transport in fetal rat lung: a sexual dimorphism.
AB  - Male fetuses exhibit delayed lung maturation and surfactant production in
      comparison with female fetuses. This delay may be related to sex hormone effects:
      estrogen enhances and androgens delay lung development. The uptake of glucose, an
      important precursor for surfactant synthesis, may be differently affected by
      estrogen and androgens. In these studies we determined the effects of these two
      hormones on glucose transport (glucose uptake, glucose transporter [Glut] 1
      protein, and mRNA) and hexokinase activity in lung tissue of fetal rats. On Day
      20 of gestation (term = 21.5 d) lung tissue was harvested from female and male
      fetal rats, minced into explants, and cultured for 24 h. Basal glucose uptake,
      measured in the absence of sex hormones, was 37% higher (P < 0.05) in female
      compared with male lungs. Explants were washed and cultured for an additional 3 h
      or 24 h in either estradiol or dihydrotestosterone (DHT) at 0, 1, 10, or 100 nM.
      Twenty-four-hour treatment with estradiol in both male and female explants
      increase 2-deoxyglucose uptake, Glut 1 protein, and mRNA levels (P < 0.05).
      However, explants from male fetuses were not as responsive to estradiol treatment
      as were those from females (P < 0.05). Treatment for 24 h with DHT decreased 2
      deoxyglucose uptake, Glut 1 protein, and mRNA levels in females and males (P <
      0.05). There was no difference in response between females and males. Short-term
      incubation (3 h) with sex hormones had no effect on glucose uptake. However, 3-h
      treatment with estradiol did increase Glut 1 mRNA levels (P < 0.05). Hexokinase
      activity was not affected by estradiol or DHT treatment. These findings indicate
      that estradiol and DHT differentially regulate glucose uptake in fetal rat lung
      tissue. This regulation of substrate supply (glucose) by estradiol and DHT may be
      another mechanism for the sexual dimorphism observed in lung development and
      surfactant synthesis.

PMID- 9651182
TI  - A correlation between epithelial proliferation rates, basement membrane component
      localization patterns, and morphogenetic potential in the embryonic mouse lung.
AB  - Lung epithelial branching morphogenesis results from a repetitive series of cleft
      and bud formation, a process dependent upon a complex interaction with the
      surrounding mesenchyme. The present study describes these cleft- and bud-forming
      regions as autonomous morphogenetic compartments within the embryonic day 11.5
      (E11.5) mouse lung and directly correlates their identity with differences in
      epithelial proliferation rates and the localization pattern of specific basement
      membrane components. Lung buds were cultured in vitro, in two-dimensional planes,
      and labeled with a series of 5-bromo-2'-deoxyuridine (BrdU) pulses. Collectively,
      epithelial cells within actively budding regions of the bronchiolar tree
      demonstrated an at least 2.5-fold greater proliferation rate than those situated
      in the adjacent cleft-forming regions. Epithelial proliferation rates showed an
      inverse relationship with the degree of immunoreactivity of nidogen, laminin-1,
      fibronectin, and collagen IV within the underlying basement membrane. Epithelial
      cells dissected free from mesenchyme demonstrated cell-cell contact-dependent
      proliferation, thus revealing a hierarchy between mesenchymal signaling and
      direct epithelial cell-cell communication during branch formation. Dissection of
      the E11.5 bronchiolar tree into specific distalbud and interbud regions and their
      in vitro culture demonstrated differences in their autonomous morphogenetic
      potential. Tissue dissected from the distal tips of the lung continued to branch,
      whereas tissue dissected from immediately adjacent cleft regions seldom branched.
      Isolated distalbud tissue also continued to correlate regional differences in
      epithelial proliferation rates and immunolocalization patterns of nidogen,
      laminin-1, fibronectin, and collagen IV with branch formation. These results
      support the basement membrane remodeling hypothesis, thus connecting nidogen,
      collagen type IV, fibronectin, and laminin-1 localization with the molecular
      processes directing epithelial proliferation and supporting bud outgrowth and
      cleft formation/stabilization during lung morphogenesis.

PMID- 9651183
TI  - Localization of Staphylococcus aureus in infected airways of patients with cystic
      fibrosis and in a cell culture model of S. aureus adherence.
AB  - Staphylococcus aureus causes chronic respiratory tract infections in patients
      with cystic fibrosis (CF). Using immunofluorescence and scanning and transmission
      electron microscopy we located S. aureus in lung specimens of three infected CF
      patients, in a nasal polyp of one CF patient, and in a suspension cell culture
      system of primary nasal epithelial cells in vitro. Very little of S. aureus was
      attached to the lung epithelium, whereas abundant S. aureus was detectable in the
      mucus of obstructed airways. Similarly, S. aureus adhered to components of
      secreted mucus on primary nasal epithelial cells of CF patients and healthy
      control subjects, grown as cell balls in vitro (bacteria/cell +/- SD: CF: 21.9 +/
      1.5; controls: 22. 0 +/- 5.8). Mucus depletion of cell balls prior to incubation
      with S. aureus resulted in a significantly reduced binding (bacteria/cell +/- SD:
      CF: 4.2 +/- 0.3; P < 0.001; controls: 5.0 +/- 1.3; P < 0. 007). Binding of S.
      aureus to cell balls from CF patients or control subjects did not differ
      significantly. When cell balls were treated with human neutrophil elastase,
      hypersecretion caused removal of S. aureus from cell-associated mucus. The
      results suggest that S. aureus adheres primarily to mucus components of the
      respiratory epithelium and that significant differences do not exist in binding
      of S. aureus to CF or non-CF cells.

PMID- 9651184
TI  - Expression of the high-affinity receptor for IgE on bronchial epithelial cells of
      asthmatics.
AB  - Bronchial epithelial cells are the first cells to come into contact with inhaled
      pneumoallergens. It has been suggested that these cells may play an important
      role in the allergic response, and indeed bronchial epithelial cells of some
      atopic asthmatic subjects have been shown to express the low-affinity receptor
      for IgE on their surface. In this report we demonstrate, using bronchial
      biopsies, that bronchial epithelial cells of some asthmatic subjects express both
      the alpha and gamma chains of the high-affinity receptor for IgE (Fcepsilon RI)
      on their surface and that they are capable of fixing IgE. Second, using reverse
      transcription-polymerase chain reaction, we show that both control and asthmatic
      subjects have messenger RNA for Fcepsilon RI. Finally, we demonstrate that this
      receptor may be functional since stimulation of the cells with the antibody to
      the alpha chain of Fcepsilon RI results in the liberation of 15
      hydroxyeicosatetraenoic acid from epithelial cells of asthmatic, but not control,
      subjects or subjects suffering from chronic bronchitis. These data suggest that
      bronchial epithelial cells from at least some asthmatic subjects express a
      functional high-affinity receptor for IgE and it is therefore possible that these
      cells may be able to interact directly with inhaled allergens.

PMID- 9651185
TI  - Air pollution particles induce IL-6 gene expression in human airway epithelial
      cells via NF-kappaB activation.
AB  - Fine particles in the air have been associated with increased mortality and
      morbidity. Particulate air pollution is a complex mixture which varies by region
      and includes a number of components including residual oil fly ash (ROFA), a
      byproduct of power plant and industry fuel-oil combustion. Human airway
      epithelial cells exposed to ROFA release inflammatory cytokines including
      interleukin (IL)-6, IL-8, and tumor necrosis factor. Expression of these genes is
      dependent upon pretranscriptional binding of cis regulatory elements, including
      nuclear factor kappaB (NF-kappaB). To investigate the role of NF-kappaB in the
      particulate-induced IL-6 response, we exposed human airway epithelial cells (BEAS
      2B) to ROFA in vitro. ROFA stimulated a time- and dose-dependent increase in IL-6
      messenger RNA (mRNA), which was preceded by the activation of nuclear proteins
      binding to the NF-kappaB sequence motif in the IL-6 promoter. Transient
      transfection of BEAS-2B cells with the 5' promoter region of the IL-6 gene linked
      to a luciferase reporter gene confirmed that NF-kappaB binding is necessary for
      the transcription of IL-6 mRNA. The IL-6 response was inhibited by the metal
      chelator deferoxamine and the free radical scavenger N-acetyl-L-cysteine,
      suggesting that the activation of NF-kappaB may be mediated through reactive
      oxygen intermediates generated by transition metals found in ROFA. Activation of
      NF-kappaB may therefore be a critical first step in the inflammatory cascade
      following exposure to particles generated by oil combustion.

PMID- 9651186
TI  - Identification of a novel alternatively spliced mRNA of murine pulmonary
      surfactant protein B.
AB  - An alternatively spliced mRNA of pulmonary surfactant protein B (SP-B) was
      identified in murine lung. Sequencing analysis revealed a 69 base-pair (bp)
      deletion at the beginning of exon 7 of SP-B, presumably the result of an
      alternative splicing event. Reverse transcription-polymerase chain reaction (RT
      PCR) of mouse, rat, and rabbit lung RNA revealed the existence of full-length and
      the 69-bp deleted short form. Ribonuclease protection assay of the SP-B messenger
      RNA (mRNA) demonstrated expression of both isoforms in five strains of adult and
      fetal mice with different genetic backgrounds, as well as in rabbit, but not in
      human. Splice junction sequences in exon 6 and at the exon 7 splice boundary for
      the two isoforms are similar, including AG doublet identity, but sequence
      differences do not account for species variation in isoform abundance. The
      abundance of the short SP-B mRNA isoform was approximately 30% of total SP-B mRNA
      in mouse and rabbit. Analysis of precursor SP-B protein in mouse lung suggested
      that the two mRNA species are expressed as stable protein isoforms.

PMID- 9651187
TI  - Susceptibility of heterozygous MnSOD gene-knockout mice to oxygen toxicity.
AB  - Recent studies have shown that homozygous Mn superoxide dismutase (Sod2) gene
      knockout mice (Sod2(-/-)) die shortly after birth with extensive myocardial
      injury, whereas heterozygous mutants (Sod2(+/-)) are phenotypically normal in
      room air. In the current study, we showed that Sod2(+/-) mice with approximately
      50% of normal pulmonary MnSOD activity and normal levels of lung CuZnSOD,
      catalase, and glutathione peroxidase activities were not substantially more
      susceptible to 100% O2 toxicity than their normal Sod2(+/+) littermates. The mean
      (+/- SD) survival of Sod2(+/-) mice in 100% O2 was 101.4 +/- 14.8 h (n = 20)
      versus 103.2 +/- 11.3 h (n = 20) for Sod2(+/+) littermates (P > 0.60). In
      addition, Sod2(+/-) mice with approximately 50% of normal heart MnSOD activity
      and Sod2(+/+) mice did not develop any ultrastructural abnormalities in the
      myocardium at 75 h or 90 h after 100% O2 exposure. These results suggest that in
      mice, only 50% of MnSOD activity may be sufficient for normal resistance to 100%
      O2 toxicity.

PMID- 9651188
TI  - Tissue sources of cytochrome P450 4A and 20-HETE synthesis in rabbit lungs.
AB  - We previously reported that 20-hydroxyeicosatetraenoic acid (20-HETE) is an
      endogenous cytochrome P450 (cP450) 4A metabolite of arachidonic acid (AA) in
      human lung tissue, and is a potent cyclooxygenase-dependent vasodilator of
      isolated pulmonary arteries. In the present investigations, we identified sources
      of cP450 4A immunospecific protein, messenger RNA (mRNA), and 20-HETE synthesis
      in rabbit lungs. Microsomes of peripheral lung tissue, airways, small and large
      vessels, and lysates of alveolar macrophages all express proteins of
      approximately 50 kD which cross-reacted with a primary antibody raised against
      rat liver cP450 4A1. Peripheral lung tissue, small and large pulmonary arteries,
      airways, and isolated vascular smooth muscle cells from small pulmonary arteries
      produced 20-HETE when incubated with AA. Expression of cP450 4A6/4A7 mRNA was
      readily detectable by reverse transcription-polymerase chain reaction using
      isoform-specific probes and 5 microg total RNA extracted from microdissected
      small pulmonary arteries. These data demonstrate that small pulmonary arteries
      express cP450 4A proteins and vascular smooth muscle cells derived from these
      arteries synthesize 20-HETE. Furthermore, cP450 4A appears to be widely
      distributed in rabbit tissue, raising the possibility that 20-HETE generated from
      nonvascular tissue could serve as a paracrine factor in the pulmonary
      circulation.

PMID- 9651189
TI  - Prolonged cell-cycle arrest associated with altered cdc2 kinase in monocrotaline
      pyrrole-treated pulmonary artery endothelial cells.
AB  - Monocrotaline pyrrole (MCTP), a metabolite of the pyrrolizidine alkaloid
      monocrotaline, is thought to initiate damage to pulmonary endothelial cells
      resulting in delayed but progressive pulmonary interstitial edema, vascular wall
      remodeling, and increasing pulmonary hypertension. MCTP was previously shown to
      inhibit pulmonary endothelial cell proliferation and cause cell-cycle arrest in
      vitro. To determine the persistence of arrest and better characterize the cell
      cycle stage at which it occurs, bovine pulmonary artery endothelial cells (BPAEC)
      under differing growth conditions were exposed to low (5 microg/ml) or high (34.5
      microg/ml) concentrations of MCTP for varying times. Flow cytometric cell-cycle
      analysis was coupled with Western blot and biochemical analysis of cdc2 kinase
      and measurements of cell size. MCTP treatment induced a G2 + M phase arrest in 48
      h exposed confluent BPAEC that persisted for at least 28 d and was associated
      with continued cellular enlargement. A short-duration MCTP exposure of confluent
      (low and high concentration) and log phase (high concentration) BPAEC caused
      persistent cell-cycle arrest for 1 wk, whereas a low-concentration exposure in
      log phase cells resulted in cell-cycle arrest with reversal 96 h after exposure.
      Western blot examination revealed that by 24 h of MCTP exposure, the
      phosphorylation state of cdc2 was consistent with the inactive form of the kinase
      (confirmed by biochemical assay); this alteration persisted through at least 96 h
      of exposure. We conclude that MCTP induces a progressive irreversible endothelial
      cell dysfunction leading to inactivation of cdc2 kinase and irreversible cell
      cycle arrest at the G2 checkpoint.

PMID- 9651190
TI  - Evidence against a role of mouse, rat, and two cloned human t1alpha isoforms as a
      water channel or a regulator of aquaporin-type water channels.
AB  - T1alpha is a protein of unknown function that is expressed at the plasma membrane
      in epithelia involved in fluid transport, including type I alveolar epithelial
      cells, choroid plexus, and ciliary epithelium. The purpose of this study was to
      test the hypothesis that T1alpha functions as a water channel or a regulator of
      aquaporin-type water channels that are coexpressed with T1alpha. Two
      complementary DNAs (cDNAs) (hT1alpha-1 and hT1alpha-2) encoding human isoforms of
      T1alpha were cloned by homology to the rat T1alpha coding sequence. The cDNAs
      encoded 164 (hT1alpha-1) and 162 (hT1alpha-2) amino acid proteins with high
      homology to rat T1alpha in a putative membrane-spanning domain. hT1alpha-1
      transcripts of 2. 6 and 1.4 kb were detected in human lung, heart, and skeletal
      muscle, and a single hT1alpha-2 transcript of 1.2 kb was detected in human lung.
      Rat and mouse T1alpha were isolated by reverse transcription-polymerase chain
      reaction and confirmed by DNA sequence analysis. Expression of mouse, rat, and
      human T1alpha isoforms in Xenopus oocytes did not increase osmotic water
      permeability (Pf) above that in water-injected oocytes, nor was there an effect
      of protein kinase A or C activation; Pf was increased > 10-fold in positive
      control oocytes expressing aquaporin (AQP)1 or AQP5. Coexpression of AQP1 or AQP5
      with excess T1alpha gave Pf not different from that in oocytes expressing AQP1 or
      AQP5 alone. Oocyte plasma membrane localization of epitope-tagged T1alpha protein
      was confirmed and quantified by immunoprecipitation of microdissected plasma
      membranes. Quantitative densitometry indicated that the single-channel water
      permeability of T1alpha is under 2 x 10(-16) cm3/s, suggesting that T1alpha is
      not involved in the high transalveolar water permeability in intact lung. The
      cloning of hT1alpha isoforms may permit the development of an assay of type I
      cell antigen in airspace fluid as a marker of human lung injury.

PMID- 9651191
TI  - Platelet-activating factor mediates intercellular adhesion molecule-1-dependent
      radical production in the nonhypoxic ischemia rat lung.
AB  - It has been reported that reperfusion is the most important factor in ischemia
      reperfusion (I/R) injury. However, causes of I/R injury in the lung are
      controversial, because oxygen is always supplied if ventilation continues.
      Therefore, we hypothesized that nonhypoxic ischemia without reperfusion is
      sufficient for lung injury. To test our hypothesis, we measured both hydrogen
      peroxide (H2O2) production in the pulmonary circulation, by digital imaging
      fluorescent dichlorofluorescein, and microvascular permeability (MVP), by the
      Evans blue extravasation technique in the nonhypoxic ischemia rat lung. We made a
      nonhypoxic ischemia rat lung by clamping the left pulmonary artery. Both H2O2
      production and MVP increased in the nonhypoxic ischemia rat lung. We also
      determined the effect of oxygen removal by clamping the bronchus in advance of
      pulmonary artery occlusion, intercellular adhesion molecule-1 (ICAM-1)
      neutralization with monoclonal antibody 1A29, and platelet-activating factor
      (PAF) receptor antagonist CV6209 on H2O2 production and MVP. These treatments
      inhibited both H2O2 production and MVP increase. At high-power viewing of the
      fluorescent dichlorofluorescein image, H2O2 was detected in the leukocytes within
      pulmonary capillaries. These data indicate that the nonhypoxic ischemia without
      reperfusion alone causes radical production and increases MVP. Furthermore, PAF
      and ICAM-1 contribute to these reactions.

PMID- 9651192
TI  - Granulocyte macrophage colony-stimulating factor augments ICAM-1 and VCAM-1
      activation of eosinophil function.
AB  - Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1
      (VCAM-1) are members of the immunoglobulin superfamily adhesion molecules on
      vascular endothelium and important in the development of eosinophil (EOS)
      accumulation in allergic inflammation. To define the role of these adhesion
      proteins in EOS inflammation, peripheral blood EOS from allergic donors were
      incubated in either buffer (control)-, recombinant human (rh)-VCAM-1-, or rh-ICAM
      1-coated plates, and the effects of these adhesion proteins on EOS effector
      functions were determined. VCAM-1 induced spontaneous EOS adhesion whereas EOS
      adhesion to ICAM-1 required a second signal, such as granulocyte macrophage
      colony-stimulating factor (GM-CSF). Although only VCAM-1 stimulated EOS
      superoxide anion (O2-) generation, the addition of GM-CSF (100 pM) to the
      reactions resulted in a greater and equivalent production of O2- with VCAM-1 and
      ICAM-1. In the presence of GM-CSF, ICAM-1 and VCAM-1 caused significant release
      of EOS-derived neurotoxin (EDN). Moreover, only ICAM-1 (no GM-CSF) promoted
      calcium ionophore A23187 (0.2 microM)-induced EOS leukotriene C4 (LTC4). Enhanced
      O2- generation, EDN release, and LTC4 generation observed with ICAM-1 and VCAM-1
      were significantly inhibited by anti-beta2-integrin antibody. These results
      suggest that ICAM-1 and VCAM-1 are important in determining the eventual function
      of airway EOS.

PMID- 9651193
TI  - Granulocyte colony-stimulating factor induces neutrophil sequestration in rabbit
      lungs.
AB  - The effects of intravenous injection of recombinant human granulocyte colony
      stimulating factor (rhG-CSF) on circulating neutrophil numbers, pulmonary
      vascular permeability, and morphologic changes in the lung were examined in
      rabbits. Intravenous injection of rhG-CSF caused a rapid, profound neutropenia
      due to neutrophil sequestration primarily within capillaries but also in larger
      microvessels of the lungs. Examination of neutrophil deformability using
      microfilters revealed that granulocyte colony-stimulating factor (G-CSF)
      treatment caused a rapid stiffening of neutrophils through the polymerization of
      F-actin but not microtubule assembly. The expression of CD11b, CD11c, and CD18 on
      human neutrophils after G-CSF treatment increased, but CD11a did not. Intravenous
      injection of rhG-CSF did not induce neutrophil emigration or albumin leakage into
      alveolar space, wet/dry lung weight ratios were unchanged, and no pathologic
      changes in lung histology were observed. These studies indicate that injection of
      rhG-CSF caused a rapid neutropenia and neutrophil sequestration in the lungs that
      is likely to be mediated through a G-CSF-induced decrease in neutrophil
      deformability, although neutrophil-endothelial cell adhesion may also play a
      role. However, this G-CSF-induced neutrophil sequestration did not induce a
      massive lung injury.

PMID- 9651194
TI  - Contribution of subsaturating GABA concentrations to IPSCs in cultured
      hippocampal neurons.
AB  - The time course of EPSCs and IPSCs is at least partly determined by the
      concentration profile of neurotransmitter acting on postsynaptic receptors.
      Several recent reports have suggested that the peak synaptic cleft concentration
      of the inhibitory neurotransmitter GABA likely reaches at least 500 microM, a
      level that saturates the GABAA receptor. In the course of investigating the
      experimental anticonvulsant 3,3-diethyl-2-pyrrolidinone (diethyl-lactam), we have
      observed an important contribution to IPSC decay by subsaturating concentrations
      of GABA. Diethyl-lactam augments currents elicited by the exogenous application
      of subsaturating concentrations of GABA in voltage-clamped, cultured hippocampal
      neurons and significantly prolongs the decay of autaptic IPSCs and miniature
      IPSCs in our cultures. In addition, diethyl-lactam potentiates currents in
      excised outside-out membrane patches elicited by the prolonged application of low
      concentrations of GABA. However, when patches are exposed to 1-2 msec pulses of 1
      mM GABA, diethyl-lactam does not alter current decay. Tiagabine, which blocks
      GABA reuptake, does not prolong IPSCs, so it is unlikely that uptake inhibition
      accounts for the enhancement of IPSCs. EPSCs and miniature IPSC frequency are
      unaffected by diethyl-lactam, again consistent with a postsynaptic site of
      action. We propose that during an IPSC, a substantial number of postsynaptic
      receptors must be exposed to subsaturating concentrations of GABA. A simplified
      model of GABAA receptor kinetics can account for the effects of diethyl-lactam on
      exogenous GABA and IPSCs if diethyl-lactam has its main effect on the
      monoliganded states of the GABAA receptor.

PMID- 9651195
TI  - Neuroprotective actions of dipyridamole on cultured CNS neurons.
AB  - We report that dipyridamole is neuroprotective for a variety of rat embryonic CNS
      neurons cultured in serum-free basal medium lacking trophic factors or other
      additives. We also describe the mechanism underlying this action. Neurons died
      rapidly in basal medium but were rescued in large measure by 10 microM
      dipyridamole. The protective action of dipyridamole seems to be attributable to
      its antioxidant property. Vitamin E and N-acetylcysteine provided comparable
      neuroprotection in basal medium, whereas an array of compounds that mimic other
      actions of dipyridamole (inhibition of phosphodiesterases, blockade of nucleoside
      and chloride transport, interference with the multidrug resistance protein, and
      enhancement of prostacyclin synthesis) failed to promote survival. Thus, a major
      cause of neuronal death in this system seems to be oxidative stress that is
      relieved by dipyridamole. Iron plays a significant role in generation of such
      stress, as indicated by the observations that addition of apotransferrin or iron
      chelators to basal medium or use of iron-free medium also afforded protection.
      Although oxidative stress was a major determinant of neuronal death, it was not
      the only factor. Dipyridamole or other antioxidant measures did not provide
      sustained neuroprotection. However, provision of insulin, which was not
      protective alone in basal medium, along with dipyridamole significantly enhanced
      long-term neuronal survival. Hence, optimal protection requires both trophic
      support and relief from oxidative stress. These findings lend credence to the
      potential use of dipyridamole or its derivatives in prevention and/or treatment
      of CNS injuries and degenerative disorders in which oxidative stress is a
      significant component.

PMID- 9651196
TI  - Lasting N-terminal phosphorylation of c-Jun and activation of c-Jun N-terminal
      kinases after neuronal injury.
AB  - Transcription factor c-Jun is proposed to control neuronal cell death and
      survival, but its activation by N-terminal phosphorylation and the underlying
      activity of the c-Jun N-terminal kinases (JNKs) remain to be elucidated in the
      adult mammalian brain. We generated a polyclonal antiserum that specifically
      recognizes c-Jun phosphorylated at its serine 73 (S73) residue after UV
      irradiation of 3T3 cells. Disruption of the c-jun locus in 3T3 cells abolished
      this reaction, and retransfection of the human c-jun at the c-jun-/- background
      restored it. The phospho-c-Jun antiserum was used to visualize N-terminally
      phosphorylated c-Jun in the adult rat brain with cellular resolution. Prolonged c
      Jun S73 phosphorylation was detected in affected neurons up to 5 d after
      transient occlusion of medial cerebral artery or up to 50 d after transection of
      central nerve fiber tracts. After cerebral ischemia-reperfusion, phosphorylation
      of c-Jun was linked with induced expression of Fas-ligand (APO-1, CD95-ligand),
      whose gene is a putative c-Jun/AP-1 target, and with terminal deoxynucleotidyl
      transferase-mediated biotinylated UTP nick end labeling (TUNEL) reactivity, a
      marker for apoptosis. After nerve fiber transection, however, lasting c-Jun
      phosphorylation occurred in axotomized neurons negative for Fas-ligand or TUNEL
      and regardless of degeneration or survival. In contrast to these lasting
      phosphorylation patterns, transient seizure activity by pentylenetetrazole
      provoked only a brief c-Jun phosphorylation and JNK activation. In extracts from
      ischemic or axotomized brain compartments, c-Jun phosphorylation correlated with
      enhanced long-term JNK activity, and in-gel kinase assays visualized proteins
      with sizes corresponding to JNK isoforms as the only c-Jun N-terminally
      phosphorylating enzymes. These results demonstrate that lasting c-Jun S73
      phosphorylation and JNK activity are part of neuronal stress response after
      neurodegenerative disorders in the adult mammalian brain with Fas-ligand as a
      putative apoptotic effector.

PMID- 9651197
TI  - Electrophysiological characterization of a putative supporting cell isolated from
      the frog taste disk.
AB  - Chemosensory cells in vertebrate taste organs have two obvious specializations:
      an apical membrane with access to the tastants occurring in food, and synapses
      with sensory axons. In many species, however, certain differentiated taste cells
      have access to the tastants but lack any synaptic contacts with axons, and a
      supportive rather than chemosensory function has been attributed to them. Until
      now, no functional data are available for these taste cells. To begin to
      understand their role in taste organ physiology, we have characterized with patch
      clamp recording techniques the electrophysiological properties of a putative
      supporting cell-the so-called wing cell-isolated from frog taste disks. Wing
      cells were distinguished from chemosensory elements by the presence of a typical,
      sheet-like apical process. Their resting potential was approximately -52 mV, and
      the average input resistance was 4.8 GOmega. Wing cells possessed voltage-gated
      Na+ currents sensitive to TTX, and an inactivating, voltage-gated K+ current
      sensitive to TEA. Current injections elicited single action potentials but not
      repetitive firing. We found no evidence for voltage-gated Ca2+ currents under
      various experimental conditions. Amiloride-sensitive Na+ channels, thought to be
      involved in Na+ chemotransduction, were present in wing cells. Many of the
      membrane properties of wing cells have been also reported for chemosensory taste
      cells. The presence of ion channels in wing cells might be suggestive of a role
      in controlling the microenvironment inside the taste organs or the functioning of
      chemosensory cells or both. In addition, they might participate directly in the
      sensory transduction events by allowing loop currents to flow inside the taste
      organs during chemostimulation.

PMID- 9651198
TI  - Cyclosporin A, but not FK 506, protects mitochondria and neurons against
      hypoglycemic damage and implicates the mitochondrial permeability transition in
      cell death.
AB  - Induction of the mitochondrial permeability transition (MPT) has been implicated
      in cellular apoptosis and in ischemia-reperfusion injury. During MPT, a channel
      in the inner mitochondrial membrane, the mitochondrial megachannel, opens and
      causes isolated mitochondria to swell. MPT and mitochondrial swelling is
      inhibited by cyclosporin A (CsA), which may also inhibit apoptosis in some cells.
      Treatment with CsA (50 mg/kg, i.v.) showed a robust reduction of brain damage
      when administered 30 min before insulin-induced hypoglycemic isoelectricity of 30
      min duration. Ultrastructural examination of the dentate gyrus revealed a marked
      swelling of dendrites and mitochondria during the hypoglycemic insult. In CsA
      treated animals, mitochondria resumed a normal and contracted appearance during
      and after the hypoglycemic insult. Treatment with FK 506 (2 mg/kg, i.v.), a
      compound with immunosuppressive action similar to that of CsA, was not
      protective. Studies on the swelling kinetics of isolated mitochondria from the
      hippocampus showed that CsA, but not FK 506, inhibits calcium ion-induced MPT. We
      conclude that CsA treatment during hypoglycemic coma inhibits the MPT and reduces
      damage and that mitochondria and the MPT are likely to be involved in the
      development of hypoglycemic brain damage in the rat.

PMID- 9651199
TI  - Neuromodulators enhance transmitter release by two separate mechanisms at the
      inhibitor of crayfish opener muscle.
AB  - A presynaptic voltage control method has been used to investigate the modulatory
      effects of serotonin (5-HT) and okadaic acid (OA) on the inhibitory junction of
      the crayfish opener muscle. Instead of using action potentials, we used 20 msec
      pulses depolarized to 0 mV to activate transmitter release. This approach allowed
      us to monitor two separate physiological parameters related to the release
      process. The first parameter, transmitter release kinetics, is characterized as
      the delay when inhibitory postsynaptic conductance reaches its half-maximum
      (IPSG50). The second parameter, the total area of IPSG (IPSGarea), estimates
      total transmitter output. We have reported previously that the F2 component of
      synaptic facilitation is associated with a decrease in IPSG50 but without a
      change in IPSGarea. These results raised the possibility that IPSG50 and IPSGarea
      could be mediated by separate mechanisms that were modulated independently. To
      explore this possibility, we investigated the effects of 5-HT (100-200 nM) and OA
      (2.5 microM) on the two parameters. 5-HT and OA enhanced IPSG neither by changing
      the sensitivity of postsynaptic receptors, as tested by iontophoretically ejected
      GABA, nor by elevating resting and action potential-activated presynaptic free
      calcium, as monitored by fura-2 imaging. 5-HT and OA decreased IPSG50 by 3.0 +/-
      1.4 and 3.6 +/- 1.1 msec, respectively, and increased IPSGarea by 50 +/- 21 and
      37 +/- 6%, respectively. The ability of F2 facilitation to accelerate release
      kinetics was reduced in the presence of the modulators, suggesting that the
      mechanism underlying the accelerated release kinetics was shared by the two modes
      of synaptic enhancement. This report demonstrates that the acceleration in
      release kinetics and the increase in total release are two separate mechanisms
      for enhancing transmitter output and that these two mechanisms can be activated
      without changes in presynaptic calcium dynamics.

PMID- 9651200
TI  - P2Y2 nucleotide receptors expressed heterologously in sympathetic neurons inhibit
      both N-type Ca2+ and M-type K+ currents.
AB  - The P2Y2 receptor is a uridine/adenosine triphosphate (UTP/ATP)-sensitive G
      protein-linked nucleotide receptor that previously has been reported to stimulate
      the phosphoinositide signaling pathway. Messenger RNA for this receptor has been
      detected in brain tissue. We have investigated the coupling of the molecularly
      defined rat P2Y2 receptor to neuronal N-type Ca2+ channels and to M-type K+
      channels by heterologous expression in rat superior cervical sympathetic (SCG)
      neurons. After the injection of P2Y2 cRNA, UTP inhibited the currents carried by
      both types of ion channel. As previously reported [Filippov AK, Webb TE, Barnard
      EA, Brown DA (1997) Inhibition by heterologously expressed P2Y2 nuerones. Br J
      Pharmacol 121:849-851], UTP inhibited the Ca2+ current (ICa(N)) by up to 64%,
      with an IC50 of approximately 0.5 microM. We now find that UTP also inhibited the
      K+M current (IK(M)) by up to 61%, with an IC50 of approximately 1.5 microM. UTP
      had no effect on either current in neurons not injected with P2Y2 cRNA. Structure
      activity relations for the inhibition of ICa(N) and IK(M) in P2Y2 cRNA-injected
      neurons were similar, with UTP >/= ATP > ITP >> GTP,UDP. However, coupling to
      these two channels involved different G-proteins: pretreatment with Pertussis
      toxin (PTX) did not affect UTP-induced inhibition of IK(M) but reduced inhibition
      of ICa(N) by approximately 60% and abolished the voltage-dependent component of
      this inhibition. In unclamped neurons, UTP greatly facilitated depolarization
      induced action potential discharges. Thus, the single P2Y2 receptor can couple to
      at least two G-proteins to inhibit both Ca2+N and K+M channels with near-equal
      facility. This implies that the P2Y2 receptor may induce a broad range of
      effector responses in the nervous system.

PMID- 9651201
TI  - Dopamine D1-like receptor activation excites rat striatal large aspiny neurons in
      vitro.
AB  - The aim of this study was to elucidate electrophysiologically the actions of
      dopamine and SKF38393, a D1-like dopamine receptor agonist, on the membrane
      excitability of striatal large aspiny neurons (cholinergic interneurons). Whole
      cell and perforated patch-clamp recordings were made of striatal cholinergic
      neurons in rat brain slice preparations. Bath application of dopamine (1-100
      microM) evoked a depolarization/inward current with an increase, a decrease, or
      no change in membrane conductance in a dose-dependent manner. This effect was
      antagonized by SCH23390, a D1-like dopamine receptor antagonist. The current
      voltage relationships of the dopamine-induced current determined in 23 cells
      suggested two conductances. In 10 cells the current reversed at -94 mV,
      approximately equal to the K+ equilibrium potential (EK); in three cells the I-V
      curves remained parallel, whereas in 10 cells the current reversed at -42 mV,
      which suggested an involvement of a cation permeable channel. Change in external
      K+ concentration shifted the reversal potential as expected for Ek in low Na+
      solution. The current observed in 2 mM Ba2+-containing solution reversed at -28
      mV. These actions of dopamine were mimicked by application of SKF38393 (1-50
      microM) or forskolin (10 microM), an adenylyl cyclase activator, and were blocked
      by SCH23390 (10 microM) or SQ22536 (300 microM), an inhibitor of adenylyl
      cyclase. These data indicate, first, that dopamine depolarizes the striatal large
      aspiny neurons by a D1-mediated suppression of resting K+ conductance and an
      opening of a nonselective cation channel and, second, that both mechanisms are
      mediated by an adenylyl cyclase-dependent pathway.

PMID- 9651202
TI  - Alternative RNA splicing of the NMDA receptor NR1 mRNA in the neurons of the
      teleost electrosensory system.
AB  - The sequence for cDNA encoding the NMDA receptor subunit 1 (aptNR1) of the weakly
      electric fish Apteronotus leptorhynchus has been determined. The deduced amino
      acid sequence is approximately 88% identical to other vertebrate NR1 proteins,
      with sequence homology extending to the alternatively spliced cassettes N1 and
      C1. The fish and mammalian N1 and C1 splice cassettes are identical at 20 of 21
      and 30 of 37 amino acid positions, respectively. We did not detect a C2 splice
      cassette in aptNR1 mRNA, but we did find two novel C-terminal alternative splice
      cassettes labeled C1' and C1". The relative levels of NR1 transcripts containing
      the N1 and C1 splice cassettes were determined by using RNase protection and in
      situ hybridization analysis. N1-containing mRNAs are more abundant in caudal
      brain regions, similar to the patterns reported for mammalian brain. In contrast,
      the relative levels of transcripts containing the C1 splice cassette are much
      lower in fish than in mammals, averaging only 9% for the whole brain. The levels
      of C1 splicing increased in more rostral brain regions. In situ hybridizations
      with N1- and C1-specific probes demonstrated that N1 cassette splicing occurs in
      most neurons but that C1 splicing is heterogeneous and is restricted to a subset
      of neuronal types in the electrosensory system.

PMID- 9651203
TI  - Neuronal matrix metalloproteinase-2 degrades and inactivates a neurite-inhibiting
      chondroitin sulfate proteoglycan.
AB  - Chondroitin sulfate proteoglycans (CSPGs) are implicated in the regulation of
      axonal growth. We previously reported that the neurite-promoting activity of
      laminin is inhibited by association with a Schwann cell-derived CSPG and that
      endoneurial laminin may be inhibited by this CSPG as well [Zuo J, Hernandez YJ,
      Muir D (1998) Chondroitin sulfate proteoglycan with neurite-inhibiting activity
      is upregulated after peripheral nerve injury. J Neurobiol 34:41-54]. Mechanisms
      regulating axonal growth were studied by using an in vitro bioassay in which
      regenerating embryonic dorsal root ganglionic neurons (DRGn) were grown on
      sections of normal adult nerve. DRGn achieved slow neuritic growth on sections of
      normal nerve, which was reduced significantly by treatment with metalloproteinase
      inhibitors. Similar results were obtained on a synthetic substratum composed of
      laminin and inhibitory CSPG. DRGn expressed the matrix metalloproteinase, MMP-2,
      which was transported to the growth cone. Recombinant MMP-2 inactivated the
      neurite-inhibiting CSPG without hindering the neurite-promoting potential of
      laminin. Similarly, neuritic growth by DRGn cultured on normal nerve sections was
      increased markedly by first treating the nerve sections with MMP-2. The
      proteolytic deinhibition by MMP-2 was equivalent to and nonadditive with that
      achieved by chondroitinase, suggesting that both enzymes inactivated inhibitory
      CSPG. Additionally, the increases in neuritic growth resulting from treating
      nerve sections with MMP-2 or chondroitinase were blocked by anti-laminin
      antibodies. From these results we conclude that MMP-2 provides a mechanism for
      the deinhibition of laminin in the endoneurial basal lamina and may play an
      important role in the regeneration of peripheral nerve.

PMID- 9651204
TI  - Response of thalamocortical neurons to hypoxia: a whole-cell patch-clamp study.
AB  - The effect of hypoxia (3-4 min of 95% N2, 5% CO2) on thalamocortical (TC) neurons
      was investigated using the whole-cell patch-clamp technique in rat dorsal lateral
      geniculate nucleus slices kept submerged at 32 degreesC. The predominant feature
      of the response of TC neurons to hypoxia was an increase in input conductance
      (DeltaGN = 117 +/- 15%, n = 33) that was accompanied by an inward shift in
      baseline holding current (IBH) at -65 and -57 mV (DeltaIBH = -45 +/- 6 pA, n =
      18, and -25 +/- 8 pA, n = 33, respectively) but not at -40 mV. The hypoxia
      induced increase in GN (as well as the shift in IBH) was abolished by procedures
      that are known to block Ih, i.e., bath application of 4-(N-ethyl-N-phenylamino)
      1, 2-dimethyl-6-(methylamino)-pyrimidinium chloride (100-300 microM) (DeltaGN = 5
      +/- 13%, n = 11) and CsCl (2-3 mM) (DeltaGN = 16 +/- 16%, n = 5), or low [Na+]o
      (DeltaGN = 10 +/- 10%, n = 5), whereas bath application of BaCl2 (0.1-2.0 mM) had
      no significant effect (DeltaGN = 128 +/- 14%, n = 8). The hypoxic response was
      also abolished in low [Ca+2]o (DeltaGN = 25 +/- 16%, DeltaIBH = -6 +/- 8 pA, n =
      13), but was unaffected by recording with electrodes containing EGTA (10 mM),
      BAPTA (10-30 mM), Cs+, or Cl-, as well as in the presence of external
      tetraethylammonium and 4-aminopyridine. Furthermore, preincubation of the slices
      with botulinum toxin A (100 nM), which is known to reduce Ca2+-dependent
      transmitter release, blocked the hypoxic response (DeltaGN = -3 +/- 15%, DeltaIBH
      = 10 +/- 5 pA, n = 4). We suggest that a positive shift in the voltage-dependence
      of Ih and a change in its activation kinetics, which transforms it into a fast
      activating current, may be responsible for the hypoxia-induced changes in GN and
      IBH, probably via an increase in Ca+2-dependent transmitter release.

PMID- 9651205
TI  - Preferential utilization of acetate by astrocytes is attributable to transport.
AB  - Exogenous acetate is preferentially metabolized by astrocytes in the CNS, but the
      biochemical basis for this selectivity is unknown. We observed that rat cortical
      astrocytes produce 14CO2 from 0.2 mM [14C]acetate at a rate of 0.43 nmol/min per
      milligram of protein, 18 times faster than cortical synaptosomes. Subsequent
      studies examined whether this was attributable to cellular differences in the
      transport or metabolism of acetate. The activity of acetyl-CoA synthetase, the
      first enzymatic step in acetate utilization, was greater in synaptosomes than in
      astrocytes (5.0 and 2.9 nmol/min per milligram of protein), indicating that
      slower metabolism in synaptosomes cannot be attributed to lack of enzymatic
      activity. [14C]Acetate uptake in astrocytes is rapid and time-dependent and
      follows saturation kinetics (Vmax, 498 nmol/min per milligram of protein; Km, 9.3
      mM). Uptake is inhibited stereospecifically by L-lactate as well as by pyruvate,
      fluoroacetate, propionate, and alpha-cyano-4-hydroxycinnamate (CHC). Preloading
      astrocytes with L-lactate or acetate, but not D-lactate, pyruvate, or glyoxylate,
      transaccelerates [14C]acetate uptake. Acetate uptake by astrocytes appears to be
      mediated by a carrier with properties similar to that of monocarboxylate
      transport. In contrast, studies with synaptosomes provided no evidence for time
      dependent, saturable, transaccelerated, or CHC-inhibitable uptake of
      [14C]acetate. The high rate of transport in astrocytes compared with synaptosomes
      explains the rapid incorporation of [14C]acetate into brain glutamine over
      glutamate. These findings provide support for the use of acetate as a marker for
      glial metabolism and suggest that extracellular acetate in the brain generated
      from acetylcholine and ethanol metabolism is accumulated first by astrocytes.

PMID- 9651206
TI  - The sodium channel Scn8a is the major contributor to the postnatal developmental
      increase of sodium current density in spinal motoneurons.
AB  - Sodium currents were recorded from motoneurons that were isolated from mice at
      postnatal days 0-8 (P0-P8) and maintained in culture for 12-24 hr. Motoneurons
      from normal mice exhibited a more than threefold increase in peak sodium current
      density from P0 to P8. For mice lacking a functional Scn8a sodium channel gene,
      motoneuronal sodium current density was comparable at P0 to that of normal mice
      but failed to increase from P0 to P8. The absence of Scn8a sodium channels is
      associated with the phenotype "motor end plate disease," which is characterized
      by a progressive neuromuscular failure and is fatal by 3-4 postnatal weeks. Thus,
      it appears that the development and function of mature motoneurons depends on the
      postnatal induction of Scn8a expression.

PMID- 9651207
TI  - G-Protein-dependent facilitation of neuronal alpha1A, alpha1B, and alpha1E Ca
      channels.
AB  - Modulation of neuronal voltage-gated Ca channels has important implications for
      synaptic function. To investigate the mechanisms of Ca channel modulation, we
      compared the G-protein-dependent facilitation of three neuronal Ca channels.
      alpha1A, alpha1B, or alpha1E subunits were transiently coexpressed with alpha2
      deltab and beta3 subunits in HEK293 cells, and whole-cell currents were recorded.
      After intracellular dialysis with GTPgammaS, strongly depolarized conditioning
      pulses facilitated currents mediated by each Ca channel type. The magnitude of
      facilitation depended on current density, with low-density currents being most
      strongly facilitated and high-density currents often lacking facilitation.
      Facilitating depolarizations speeded channel activation approximately 1.7-fold
      for alpha1A and alpha1B and increased current amplitudes by the same proportion,
      demonstrating equivalent facilitation of G-protein-inhibited alpha1A and alpha1B
      channels. Inactivation typically obscured facilitation of alpha1E current
      amplitudes, but the activation kinetics of alpha1E currents showed consistent and
      pronounced G-protein-dependent facilitation. The onset and decay of facilitation
      had the same kinetics for alpha1A, alpha1B, and alpha1E, suggesting that Gbeta
      gamma dimers dissociate from and reassociate with these Ca channels at very
      similar rates. To investigate the structural basis for N-type Ca channel
      modulation, we expressed a mutant of alpha1B missing large segments of the II-III
      loop and C terminus. This deletion mutant exhibited undiminished G-protein
      dependent facilitation, demonstrating that a Gbeta gamma interaction site
      recently identified within the C terminus of alpha1E is not required for
      modulation of alpha1B.

PMID- 9651208
TI  - Membrane current induced by protein kinase C activators in rhabdomeric
      photoreceptors: implications for visual excitation.
AB  - Visual excitation in rhabdomeric photoreceptors is thought to be mediated by
      activation of a light-regulated phospholipase C (PLC) and the consequent
      hydrolysis of phosphatidylinositol bisphosphate. Whereas much attention has been
      devoted to inositol trisphosphate (IP3) production and intracellular Ca2+
      release, little is known about the possible role of the DAG branch in the
      generation of the light response. We have tested the effect of chemically
      distinct surrogates of DAG on isolated Lima photoreceptors. Application of the
      phorbol ester PMA (0.5-10 microM) or the alkaloid (-)-indolactam (20-100 microM)
      from a holding potential of -50 mV elicited an inward current, several hundred
      picoamperes in amplitude, accompanied by a pronounced increase in membrane
      conductance. The stereoisomers 4alpha-PMA and (+)-indolactam were both inactive,
      arguing for the specificity of the effects. Elevation of cytosolic Ca2+ by
      intracellular dialysis accelerated this current, whereas chelerythrine
      antagonized it, suggesting the involvement of PKC. The reversal potential of the
      membrane current induced by PKC activators was approximately +10 mV; replacement
      of extracellular Na with impermeant N-methyl-D-glucamine decreased its amplitude
      and shifted the reversal potential in the negative direction. Stimulation by PMA
      and (-)-indolactam was accompanied by a pronounced depression of light
      responsiveness; conversely, steady illumination reduced the size of the current
      elicited by these PKC activators. Taken together, these results support the
      notion that the DAG branch of the PLC cascade, in addition to its suggested
      participation in visual adaptation, may play a role in the activation of the
      photoresponse or a component thereof, probably in synergy with IP3-mediated Ca2+
      release.

PMID- 9651209
TI  - The activity of a highly promiscuous AP-1 element can be confined to neurons by a
      tissue-selective repressive element.
AB  - Tissue-specific gene transcription can be determined by the use of either
      positive-acting or negative-acting DNA regulatory elements. We have analyzed a
      promoter from the growth-associated protein 43 (GAP-43) gene and found that it
      uses both of these mechanisms to achieve its high degree of neuron-specific
      activity. Two novel transcription factor binding sites, designated Cx1 and Cx2,
      drive promoter activity in neurons from developing cerebral cortex but not in
      several other cell types. The promoter also contains an activator protein 1 (AP
      1) site that contributes to activity in neurons. The AP-1 site can drive promoter
      activity in a wide range of non-neuronal cells that express little or no
      endogenous GAP-43, but only in the absence of a tissue-specific repressive
      element located downstream of the GAP-43 TATA box. These findings suggest that
      the GAP-43 repressive element plays an important role in allowing AP-1 signaling
      pathways to modulate activity of the GAP-43 gene in neurons, without also causing
      inappropriate activation by AP-1 transcription factors in other cell types.

PMID- 9651210
TI  - Withdrawal from 3alpha-OH-5alpha-pregnan-20-One using a pseudopregnancy model
      alters the kinetics of hippocampal GABAA-gated current and increases the GABAA
      receptor alpha4 subunit in association with increased anxiety.
AB  - In the present study, we have characterized properties of steroid withdrawal
      using a pseudopregnant rat model. This paradigm results in increased production
      of endogenous progesterone from ovarian sources and as such is a useful
      physiological model. "Withdrawal" from progesterone induced by ovariectomy on day
      12 of pseudopregnancy resulted in increased anxiety, as determined by a decrease
      in open arm entries on the elevated plus maze compared to control rats and
      pseudopregnant animals not undergoing withdrawal. Similar findings were obtained
      24 hr after administration of a 5alpha-reductase blocker to a pseudopregnant
      animal, suggesting that it is the GABAA-modulatory 3alpha-OH-5alpha-pregnan-20
      one (3alpha, 5alpha-THP) that produces anxiogenic withdrawal symptoms. Twenty
      four hours after steroid withdrawal, the time constant for decay of GABAA-gated
      current was also reduced sixfold, assessed using whole- cell patch-clamp
      procedures on pyramidal neurons acutely dissociated from CA1 hippocampus. Thus,
      3alpha,5alpha-THP withdrawal results in a marked decrease in total GABAA current,
      a possible mechanism for its anxiogenic, proconvulsant sequelae. In addition,
      3alpha,5alpha-THP withdrawal resulted in insensitivity to the normally
      potentiating effect of the benzodiazepine lorazepam (LZM) on GABAA-gated Cl-
      current. This withdrawal profile is similar to that reported for other GABAA
      modulatory drugs such as the benzodiazepines (BDZs), barbiturates, and ethanol.
      These changes were also associated with significant two and threefold increases
      in both the mRNA and protein for the alpha4 subunit of the GABAA receptor,
      respectively, in hippocampus. The pseudopregnancy paradigm may be a useful model
      for periods of endogenous 3alpha,5alpha-THP withdrawal such as premenstrual
      syndrome and postpartum or postmenopausal dysphoria, when increased emotional
      lability and BDZ insensitivity have been reported.

PMID- 9651211
TI  - Vasoactive intestinal peptide enhances its own expression in sympathetic neurons
      after injury.
AB  - Neurons in the adult rat superior cervical sympathetic ganglion (SCG)
      dramatically increase their content of vasoactive intestinal peptide (VIP) and
      its mRNA after axotomy in vivo and after explantation. Because the VIP gene
      contains a functional cAMP response element, the effects of cAMP-elevating agents
      on VIP expression were examined. VIP, forskolin, or isoproterenol increased cAMP
      accumulation in explanted ganglia. Secretin, a peptide chemically related to VIP,
      or forskolin increased VIP levels above those seen in ganglia cultured in control
      medium, whereas treatment with VIP or secretin increased the level of peptide
      histidine isoleucine (PHI), a peptide coded for by the same mRNA that encodes
      VIP. VIP or forskolin also increased VIP-PHI mRNA. In contrast, isoproterenol did
      not alter levels of VIP, PHI, or VIP-PHI mRNA. Although VIP or forskolin
      increased cAMP levels in both dissociated neurons and in non-neuronal cells,
      isoproterenol significantly stimulated cAMP accumulation only in the latter. VIP6
      28 was an effective antagonist of the actions of exogenous VIP on cAMP and VIP
      PHI mRNA in neuron-enriched cultures. When adult SCG explants were cultured in
      defined medium, endogenous VIP immunoreactivity was released. When VIP6-28 was
      added to such cultures, it significantly inhibited the increase in VIP-PHI mRNA
      that normally occurs. These data indicate that VIP, or a closely related
      molecule, produced by adult neurons after injury can enhance the expression of
      VIP. Such a mechanism may prolong the period during which VIP is elevated after
      axonal damage. The possibility is also discussed that, because VIP is present in
      preganglionic neurons in normal animals, its release during periods of increased
      sympathetic nerve activity could alter VIP expression in the SCG.

PMID- 9651212
TI  - Comparison of hippocampal dendritic spines in culture and in brain.
AB  - We have quantified hippocampal spine structure at the light and ultrastructural
      levels in cell cultures approximately 1- 3 weeks old and in the brains of rodents
      5 and 21 d old. The number of spines bearing synapses increases with age in
      cultures and in brain, but the structures are similar in both. In culture, about
      half of the synapses are formed on spines and the remainder are formed on
      dendritic shafts. In the 5-d-old brain, about half of the synapses occur on
      dendritic shafts, by 3 weeks of age only approximately 20% of synapses are found
      on dendritic shafts, and in the adult shaft synapses are very rare.

PMID- 9651213
TI  - A complex program of striatal gene expression induced by dopaminergic
      stimulation.
AB  - Dopamine acting in the striatum is necessary for normal movement and motivation.
      Drugs that change striatal dopamine neurotransmission can have long-term effects
      on striatal physiology and behavior; these effects are thought to involve
      alterations in gene expression. Using the 6-hydroxydopamine lesion model of
      Parkinson's disease and differential display PCR, we have identified a set of
      more than 30 genes whose expression rapidly increases in response to stimulation
      of striatal dopamine D1 receptors. The induced mRNAs include both novel and
      previously described genes, with diverse time courses of expression. Some genes
      are expressed at near-maximal levels within 30 min, whereas others show no
      substantial induction until 2 hr or more after stimulation. Some of the induced
      genes, such as CREM, CHOP, and MAP kinase phosphatase-1, may be components of a
      homeostatic response to excessive stimulation. Others may be part of a genetic
      program involved in cellular and synaptic plasticity. A very similar set of genes
      is induced in unlesioned animals by administration of the psychostimulant cocaine
      or the antipsychotic eticlopride, although in distinct striatal cell populations.
      In contrast to some previously described early genes, most of the novel genes are
      not induced in cortex by apomorphine, indicating specificity of induction. Thus
      we have identified novel components of a complex, coordinated genetic program
      that is induced in striatal cells in response to various dopaminergic
      manipulations.

PMID- 9651215
TI  - Hippocampal neurotoxicity of Delta9-tetrahydrocannabinol.
AB  - Marijuana consumption elicits diverse physiological and psychological effects in
      humans, including memory loss. Here we report that Delta9-tetrahydrocannabinol
      (THC), the major psychoactive component of marijuana, is toxic for hippocampal
      neurons. Treatment of cultured neurons or hippocampal slices with THC caused
      shrinkage of neuronal cell bodies and nuclei as well as genomic DNA strand
      breaks, hallmarks of neuronal apoptosis. Neuron death induced by THC was
      inhibited by nonsteroidal anti-inflammatory drugs, including indomethacin and
      aspirin, as well as vitamin E and other antioxidants. Furthermore, treatment of
      neurons with THC stimulated a significant increase in the release of arachidonic
      acid. We hypothesize that THC neurotoxicity is attributable to activation of the
      prostanoid synthesis pathway and generation of free radicals by cyclooxygenase.
      These data suggest that some of the memory deficits caused by cannabinoids may be
      caused by THC neurotoxicity.

PMID- 9651214
TI  - The neural cell adhesion molecule L1 interacts with the AP-2 adaptor and is
      endocytosed via the clathrin-mediated pathway.
AB  - Cell-cell interactions mediated via cell adhesion molecules (CAMs) are
      dynamically regulated during nervous system development. One mechanism to control
      the amount of cell surface CAMs is to regulate their recycling from the plasma
      membrane. The L1 subfamily of CAMs has a highly conserved cytoplasmic domain that
      contains a tyrosine, followed by the alternatively spliced RSLE (Arg-Ser-Leu-Glu)
      sequence. The resulting sequence of YRSL conforms to a tyrosine-based sorting
      signal that mediates clathrin-dependent endocytosis of signal-bearing proteins.
      The present study shows that L1 associates in rat brain with AP-2, a clathrin
      adaptor that captures plasma membrane proteins with tyrosine-based signals for
      endocytosis by coated pits. In vitro assays demonstrate that this interaction
      occurs via the YRSL sequence of L1 and the mu 2 chain of AP-2. In L1-transfected
      3T3 cells, L1 endocytosis is blocked by dominant-negative dynamin that
      specifically disrupts clathrin-mediated internalization. Furthermore, endocytosed
      L1 colocalizes with the transferrin receptor (TfR), a marker for clathrin
      mediated internalization. Mutant forms of L1 that lack the YRSL do not colocalize
      with TfR, indicating that the YRSL mediates endocytosis of L1. In neurons, L1 is
      endocytosed preferentially at the rear of axonal growth cones, colocalizing with
      Eps15, another marker for the clathrin endocytic pathway. These results establish
      a mechanism by which L1 can be internalized from the cell surface and suggest
      that an active region of L1 endocytosis at the rear of growth cones is important
      in L1-dependent axon growth.

PMID- 9651216
TI  - Regulated expression of the cell adhesion glycoprotein F3 in adult hypothalamic
      magnocellular neurons.
AB  - F3, a glycoprotein of the immunoglobulin superfamily implicated in axonal growth,
      occurs in oxytocin (OT)-secreting and vasopressin (AVP)-secreting neurons of the
      adult hypothalamo-neurohypophysial system (HNS) whose axons undergo morphological
      changes in response to stimulation. Immunocytochemistry and immunoblot analysis
      showed that during basal conditions of HNS secretion, there are higher levels of
      this glycosylphosphatidyl inositol-anchored protein in the neurohypophysis, where
      their axons terminate, than in the hypothalamic nuclei containing their somata.
      Physiological stimulation (lactation, osmotic challenge) reversed this pattern
      and resulted in upregulation of F3 expression, paralleling that of OT and AVP
      under these conditions. In situ hybridization revealed that F3 expression in the
      hypothalamus is restricted to its magnocellular neurons and demonstrated a more
      than threefold increase in F3 mRNA levels in response to stimulation. Confocal
      and electron microscopy localized F3 in secretory granules in all neuronal
      compartments, a localization confirmed by detection of F3 immunoreactivity in
      granule-enriched fractions obtained by sucrose density gradient fractionation of
      rat neurohypophyses. F3 was not visible on any cell surface in the magnocellular
      nuclei. In contrast, in the neurohypophysis, it was present not only in secretory
      granules but also on the surface of axon terminals and glia and in extracellular
      spaces. Taken together, our observations reveal that the cell adhesion
      glycoprotein F3 is colocalized with neurohypophysial peptides in secretory
      granules. It follows, therefore, the regulated pathway of secretion in HNS
      neurons to be released by exocytosis at their axon terminals in the
      neurohypophysis, where it may intervene in activity-dependent structural axonal
      plasticity.

PMID- 9651217
TI  - Identification of the dopamine D3 receptor in oligodendrocyte precursors:
      potential role in regulating differentiation and myelin formation.
AB  - Expression of the dopamine D3 receptor (D3r) was found in primary mixed glial
      cultures from newborn brain and in the corpus callosum in vivo during the peak of
      myelination. Expression of the D3r mRNA, but not D2r mRNA, was detected as early
      as 5 d in vitro (DIV) by RT-PCR. Immunoblot studies revealed D3r protein was also
      expressed in the cultures. Double immunofluorescence analysis for the D3r and for
      surface markers of specific stages of oligodendrocyte development indicated that
      D3r expression occurred in precursors and in immature oligodendrocytes but not in
      mature oligodendrocytes (i.e. , A2B5(+) 007(-) 01(-) and A2B5(+) 007(+) 01(-)
      cells but not A2B5(-) 007(+) 01(+) cells). Confocal microscopic analysis
      indicated that D3r was associated with cell bodies and cell membranes but not
      with the processes emanating from cell somas. Immunohistochemistry of brain
      sections revealed the presence of D3r in some oligodendrocytes located mainly
      within the genu and radiato of the corpus callosum during the active period of
      myelination. Treatment of cultures with 20 microM quinpirole led to decreased
      numbers of O1(+) oligodendrocytes possessing myelin-like membranes as well as an
      increase in the number of precursors in 14 DIV cultures. This effect was
      prevented by the dopamine antagonist haloperidol. These results show that the D3r
      expression is not restricted to neurons but it is also expressed in
      differentiating oligodendrocytes before terminal maturation. It also suggests
      that dopamine or some other D3r ligand may play a role in oligodendrocyte
      differentiation and/or the formation of myelin by mature oligodendrocytes.

PMID- 9651218
TI  - Neurotrophin-3 and brain-derived neurotrophic factor induce oligodendrocyte
      proliferation and myelination of regenerating axons in the contused adult rat
      spinal cord.
AB  - Functional loss after spinal cord injury (SCI) is caused, in part, by
      demyelination of axons surviving the trauma. Neurotrophins have been shown to
      induce oligodendrogliagenesis in vitro, but stimulation of oligodendrocyte
      proliferation and myelination by these factors in vivo has not been examined. We
      sought to determine whether neurotrophins can induce the formation of new
      oligodendrocytes and myelination of regenerating axons after SCI in adult rats.
      In this study, fibroblasts producing neurotrophin-3 (NT-3), brain-derived
      neurotrophic factor (BDNF), ciliary neurotrophic factor, nerve growth factor,
      basic fibroblast growth factor, or beta-galactosidase (control grafts) were
      transplanted subacutely into the contused adult rat spinal cord. At 10 weeks
      after injury, all transplants contained axons. NT-3 and BDNF grafts, however,
      contained significantly more axons than control or other growth factor-producing
      grafts. In addition, significantly more myelin basic protein-positive profiles
      were detected in NT-3 and BDNF transplants, suggesting enhanced myelination of
      ingrowing axons within these neurotrophin-producing grafts. To determine whether
      augmented myelinogenesis was associated with increased proliferation of
      oligodendrocyte lineage cells, bromodeoxyuridine (BrdU) was used to label
      dividing cells. NT-3 and BDNF grafts contained significantly more BrdU-positive
      oligodendrocytes than controls. The association of these new oligodendrocytes
      with ingrowing myelinated axons suggests that NT-3- and BDNF-induced
      myelinogenesis resulted, at least in part, from expansion of oligodendrocyte
      lineage cells, most likely the endogenous oligodendrocyte progenitors. These
      findings may have significant implications for chronic demyelinating diseases or
      CNS injuries.

PMID- 9651219
TI  - Type 1 inositol 1,4,5-trisphosphate receptor is required for induction of long
      term depression in cerebellar Purkinje neurons.
AB  - The inositol 1,4,5-trisphosphate receptor (InsP3R) is an intracellular Ca2+
      channel that releases Ca2+ from internal Ca2+ stores in response to InsP3.
      Although InsP3R is highly expressed in various regions of the mammalian brain,
      the functional role of this receptor has not been clarified. We show here that
      cerebellar slices prepared from mice with a disrupted InsP3R type 1 gene, which
      is predominantly expressed in Purkinje cells, completely lack long-term
      depression (LTD), a model of synaptic plasticity in the cerebellum. Moreover, a
      specific antibody against InsP3R1, introduced into wild-type Purkinje cells
      through patch pipettes, blocked the induction of LTD. These data indicate that,
      in addition to Ca2+ influx through Ca2+ channels on the plasma membrane, Ca2+
      release from InsP3R plays an essential role in the induction of LTD, suggesting a
      physiological importance for InsP3R in Purkinje cells.

PMID- 9651220
TI  - Patterns of intracellular calcium fluctuation in precursor cells of the
      neocortical ventricular zone.
AB  - Changes in intracellular free calcium concentration ([Ca2+]i) are known to
      influence a variety of events in developing neurons. Although spontaneous changes
      of [Ca2+]i have been examined in immature cortical neurons, the calcium dynamics
      of cortical precursor cells have received less attention. Using an intact
      cortical mantle and confocal laser microscopy, we examined the spatiotemporal
      patterns of spontaneous [Ca2+]i fluctuations in neocortical ventricular zone (VZ)
      cells in situ. The majority of activity consisted of single cells that displayed
      independent [Ca2+]i fluctuations. These events occurred in cells throughout the
      depth of the VZ. Immunohistochemical staining confirmed that these events
      occurred primarily in precursor cells rather than in postmitotic neurons. When
      imaging near the ventricular surface, synchronous spontaneous [Ca2+]i increases
      were frequently observed in pairs of adjacent cells. Cellular morphology, time
      lapse imaging, and nuclear staining demonstrated that this activity occurred in
      mitotically active cells. A third and infrequently encountered pattern of
      activity consisted of coordinated spontaneous increases in [Ca2+]i in groups of
      neighboring VZ cells. The morphological characteristics of these cells and
      immunohistochemical staining suggested that the coordinated events occurred in
      gap junction-coupled precursor cells. All three patterns of activity were
      dependent on the release of Ca2+ from intracellular stores. These results
      demonstrate distinct patterns of spontaneous [Ca2+]i change in cortical precursor
      cells and raise the possibility that these dynamics may contribute to the
      regulation of neurogenesis.

PMID- 9651221
TI  - Tlx-1 and Tlx-3 homeobox gene expression in cranial sensory ganglia and hindbrain
      of the chick embryo: markers of patterned connectivity.
AB  - Recent evidence suggests that in vertebrates the formation of distinct neuronal
      cell types is controlled by specific families of homeodomain transcription
      factors. Furthermore, the expression domains of a number of these genes
      correlates with functionally integrated neuronal populations. We have isolated
      two members of the divergent T-cell leukemia translocation (HOX11/Tlx) homeobox
      gene family from chick, Tlx-1 and Tlx-3, and show that they are expressed in
      differentiating neurons of both the peripheral and central nervous systems. In
      the peripheral nervous system, Tlx-1 and Tlx-3 are expressed in overlapping
      domains within the placodally derived components of a number of cranial sensory
      ganglia. Tlx-3, unlike Tlx-1, is also expressed in neural crest-derived dorsal
      root and sympathetic ganglia. In the CNS, both genes are expressed in
      longitudinal columns of neurons at specific dorsoventral levels of the hindbrain.
      Each column has distinct anterior and/or posterior limits that respect inter
      rhombomeric boundaries. Tlx-3 is also expressed in D2 and D3 neurons of the
      spinal cord. Tlx-1 and Tlx-3 expression patterns within the peripheral and
      central nervous systems suggest that Tlx proteins may be involved not only in the
      differentiation and/or survival of specific neuronal populations but also in the
      establishment of neuronal circuitry. Furthermore, by analogy with the LIM genes,
      Tlx family members potentially define sensory columns early within the developing
      hindbrain in a combinatorial manner.

PMID- 9651222
TI  - Localized sources of neurotrophins initiate axon collateral sprouting.
AB  - The sprouting of axon collateral branches is important in the establishment and
      refinement of neuronal connections during both development and regeneration.
      Collateral branches are initiated by the appearance of localized filopodial
      activity along quiescent axonal shafts. We report here that sensory neuron axonal
      shafts rapidly sprout filopodia at sites of contact with nerve growth factor
      coated polystyrene beads. Some sprouts can extend up to at least 60 micro(m)
      through multiple bead contacts. Axonal filopodial sprouts often contained
      microtubules and exhibited a debundling of axonal microtubules at the site of
      bead-axon contact. Cytochalasin treatment abolished the filopodial sprouting, but
      not the accumulation of actin filaments at sites of bead-axon contact. The axonal
      sprouting response is mediated by the trkA receptor and likely acts through a
      phosphoinositide-3 kinase-dependent pathway, in a manner independent of
      intracellular Ca2+ fluctuations. These findings implicate neurotrophins as local
      cues that directly stimulate the formation of collateral axon branches.

PMID- 9651223
TI  - Blocking N-cadherin function disrupts the epithelial structure of differentiating
      neural tissue in the embryonic chicken brain.
AB  - The cell adhesion molecule N-cadherin is ubiquitously expressed in the early
      neuroepithelium, with strongest expression in the ependymal lining. We blocked
      the function of N-cadherin during early chicken brain development by injecting
      antibodies against N-cadherin into the tectal ventricle of embryos at 4-5 d of
      incubation [embryonic day 4 (E4)-E5]. N-cadherin blockage results in massive
      morphological changes in restricted brain regions. At approximately E6, these
      changes consist of invaginations of pieces of the ependymal lining and the
      formation of neuroepithelial rosettes. The rosettes are composed of central
      fragments of ependymal lining, surrounded by an inner ventricular layer and an
      outer mantle layer. Radial glia processes are radially arranged around the
      ependymal centers of the rosettes. The normal layering of the neural tissue is
      thus preserved, but its coherent epithelial structure is disrupted. The observed
      morphological changes are restricted to specific brain regions such as the tectum
      and the dorsal thalamus, whereas the ventral thalamus and the pretectum are
      almost undisturbed. At E10-E11, analysis of late effects of N-cadherin blockage
      reveals that in the dorsal thalamus, gray matter is fragmented and disorganized;
      in the tectum, additional layers have formed at the ventricular surface.
      Together, these results indicate that N-cadherin function is required for the
      maintenance of a coherent sheet of neuroepithelium in specific brain regions.
      Disruption of this sheet results in an abnormal morphogenesis of brain gray
      matter.

PMID- 9651224
TI  - Role of the nucleus raphe magnus in antinociception produced by ABT-594:
      immediate early gene responses possibly linked to neuronal nicotinic
      acetylcholine receptors on serotonergic neurons.
AB  - Recently, a novel cholinergic channel modulator, (R)-5-(2-azetidinylmethoxy)-2
      chloropyridine (ABT-594), was shown to produce potent analgesia in a variety of
      rodent pain models when administered either systemically or centrally into the
      nucleus raphe magnus (NRM). The purpose of the present study was to investigate
      the possible supraspinal contribution of ABT-594 by assessing its ability to
      induce expression of the immediate early gene c-fos, a biochemical marker of
      neuronal activation, in the NRM of rats. Putative serotonergic neurons in the
      NRM, a medullary nucleus proposed to be involved in descending antinociceptive
      pathways, were identified immunohistochemically using a monoclonal antibody (mAb)
      against tryptophan hydroxylase. ABT-594 (0.03-0.3 micromol/kg, i.p.) produced a
      dose-dependent induction of Fos protein that was blocked by the central nicotinic
      acetylcholine receptor (nAChR) antagonist mecamylamine (5 micromol/kg, i.p.) but
      not by the peripheral nAChR antagonist hexamethonium (15 micromol/kg, i.p.).
      Immunohistological studies using mAb 299 revealed the expression of alpha4
      containing nAChRs in the NRM. The alpha4 immunostaining was dramatically reduced
      by pretreating (30 d) animals with the serotonin neurotoxin 5,7
      dihydroxytryptamine (5,7-DHT), which was previously shown to substantially
      attenuate the antinociceptive actions of ABT-594. In a double immunohistochemical
      labeling experiment, coexpression of the serotonin marker tryptophan hxdroxylase
      and the alpha4 nAChR subunit in NRM neurons was observed. These results suggest
      that the analgesic mechanism of ABT-594 may in part involve the activation of the
      NRM, a site where alpha4-containing nAChRs are expressed by serotonergic neurons.

PMID- 9651225
TI  - Monocular core zones and binocular border strips in primate striate cortex
      revealed by the contrasting effects of enucleation, eyelid suture, and retinal
      laser lesions on cytochrome oxidase activity.
AB  - In primate striate cortex, geniculocortical afferents in layer IVc terminate in
      parallel stripes called ocular dominance columns. We propose that this
      segregation of ocular inputs generates a related but distinct columnar system of
      monocular core zones alternating with binocular border strips. Evidence for this
      functional parcellation was obtained by comparing the effects of enucleation,
      eyelid suture, and retinal laser lesions on cytochrome oxidase (CO) activity in
      eight macaques. Enucleation produced a high-contrast pattern of dark and light
      columns in layer IVc, corresponding precisely to the ocular dominance columns,
      whereas eyelid suture produced a low-contrast pattern of thin dark columns
      alternating with wide pale columns. [3H]Proline eye injection showed that the
      thin dark columns corresponded to the core zones of the open eye's ocular
      dominance columns. The wide pale columns resulted from loss of CO activity in the
      sutured eye's core zones and within both eyes' border strips. Loss of CO activity
      within both eyes' border strips suggested that these regions are binocular. To
      confirm our findings, we compared different CO patterns in the same cortex by
      making retinal laser lesions in four animals. They produced a CO pattern
      tantamount to "focal" enucleation, although contrast was low when laser damage
      was confined to the outer retina. CO levels in cortical scotomas remained
      severely depressed for months after retinal lesions, even when the other eye was
      enucleated. This observation provided little anatomical support for the notion of
      topographic plasticity after visual deafferentation. In a single human subject
      with macular degeneration, CO revealed a low-contrast pattern of ocular dominance
      columns, resembling the pattern in monkeys with laser-induced photoreceptor
      damage.

PMID- 9651226
TI  - Leukemia inhibitory factor is an anti-inflammatory and analgesic cytokine.
AB  - The mRNA for leukemia inhibitory factor (LIF), a neuroimmune signaling molecule,
      is elevated during skin inflammation produced by intraplantar injection of
      complete Freund's adjuvant (CFA). Moreover, although LIF knock-out mice display
      normal sensitivity to cutaneous mechanical and thermal stimulation compared with
      wild-type mice, the degree of CFA-induced inflammation in mice lacking LIF is
      enhanced in spatial extent, amplitude, cellular infiltrate, and interleukin (IL)
      1beta and nerve growth factor (NGF) expression. Conversely, local injection of
      low doses of recombinant LIF diminishes mechanical and thermal hypersensitivity
      as well as the IL-1beta and NGF expression induced by CFA. These data show that
      upregulation of LIF during peripheral inflammation serves a key, early anti
      inflammatory role and that exogenous LIF can reduce inflammatory hyperalgesia.

PMID- 9651227
TI  - Anterograde signaling by nitric oxide: characterization and in vitro
      reconstitution of an identified nitrergic synapse.
AB  - Nitric oxide (NO) is recognized as a signaling molecule in the CNS where it is a
      candidate retrograde neurotransmitter. Here we provide direct evidence that NO
      mediates slow excitatory anterograde transmission between the NO synthase (NOS)
      expressing B2 neuron and an NO-responsive follower neuron named B7nor. Both are
      motoneurons located in the buccal ganglia of the snail Lymnaea stagnalis where
      they participate in feeding behavior. Transmission between B2 and B7nor is
      blocked by inhibiting NOS and is suppressed by extracellular scavenging of NO.
      Furthermore, focal application of NO to the cell body of the B7nor neuron causes
      a depolarization that mimics the effect of B2 activity. The slow interaction
      between the B2 and B7nor neurons can be re-established when the two neurons are
      cocultured, and it shows the same susceptibility to NOS inhibition and NO
      scavenging. In cell culture we have also examined spatial aspects of NO
      signaling. We show that before the formation of an anatomical connection, the
      presynaptic neuron can cause depolarizing potentials in the follower neuron at
      distances up to 50 micro(m). The strength of the interaction increases when the
      distance between the cells is reduced. Our results suggest that NO can function
      as both a synaptic and a nonsynaptic signaling molecule.

PMID- 9651228
TI  - Hypothalamic neurons preferentially respond to female nest coo stimulation:
      demonstration of direct acoustic stimulation of luteinizing hormone release.
AB  - Avian vocalizations are generally understood to play a pivotal role in
      reproductive functions. The role of the hypothalamus in gonadotropin release in
      higher vertebrates including birds is well established. To date, however, a
      direct linkage between the neuronal processing of vocal input and the contingent
      luteinizing hormone (LH) response has not been demonstrated. In this study, using
      female ring doves, we recorded neuronal activity from hypothalamic nuclei that,
      as we have shown previously, receive acoustic inputs from the auditory thalamic
      relay. Concurrently with recording single-unit responses to stimulation with
      species-specific coo vocalizations, we sampled LH levels in blood from the
      pituitary veins. LH concentration in the plasma was significantly elevated in
      birds hearing species-typical coos but not in birds exposed to experimentally
      altered coos or white noise or in birds that received no vocal stimulation. We
      found two types of neurons in the preoptic and anterior hypothalamus that
      selectively responded to the female nest coo: excitatory units and inhibitory
      units. Among the excitatory neurons are units characterized by two bursts
      separated by a period of slow spiking or complete silence, in a pattern
      approximately corresponding temporally to the two-note coo. We designate them as
      female-nest-coo-specific units. Most neurons in the posterior hypothalamus were
      nonselective in their response. Female nest coo and male nest coo stimulation
      evoked an equal magnitude of discharge changes from responsive units in the
      preoptic-anterior hypothalamic area. We found, however, that the LH increment was
      three times greater for birds hearing female nest coos than for birds hearing
      male nest coos. These observations suggest that feature-detecting neurons such as
      the female-nest-coo-specific units are involved in gonadotropin-releasing hormone
      output. The present findings are consistent with the well established behavioral
      evidence that female nest coos mediate ovarian growth.

PMID- 9651229
TI  - Behavioral state control through differential serotonergic inhibition in the
      mesopontine cholinergic nuclei: a simultaneous unit recording and microdialysis
      study.
AB  - Cholinergic neurons of the mesopontine nuclei are strongly implicated in
      behavioral state regulation. One population of neurons in the cholinergic zone of
      the laterodorsal tegmentum and the pedunculopontine nuclei, referred to as rapid
      eye movement (REM)-on neurons, shows preferential discharge activity during REM
      sleep, and extensive data indicate a key role in production of this state.
      Another neuronal group present in the same cholinergic zone of the laterodorsal
      tegmentum and the pedunculopontine nuclei, referred to as Wake/REM-on neurons,
      shows preferential discharge activity during both wakefulness and REM sleep and
      is implicated in the production of electroencephalographic activation in both of
      these states. To test the hypothesis of differential serotonergic inhibition as
      an explanation of the different state-related discharge activity, we developed a
      novel methodology that enabled, in freely behaving animals, simultaneous unit
      recording and local perfusion of neuropharmacological agents using a
      microdialysis probe adjacent to the recording electrodes. Discharge activity of
      REM-on neurons was almost completely suppressed by local microdialysis perfusion
      of the selective 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH
      DPAT), although this agonist had minimal or no effect on the Wake/REM-on neurons.
      We conclude that selective serotonergic inhibition is a basis of differential
      state regulation in the mesopontine cholinergic nuclei, and that the novel
      methodology combining neurophysiological and neuropharmacological information
      from the freely behaving animal shows great promise for further insight into the
      neural basis of behavioral control.

PMID- 9651230
TI  - Intracellular correlates of acquisition and long-term memory of classical
      conditioning in Purkinje cell dendrites in slices of rabbit cerebellar lobule
      HVI.
AB  - Intradendritic recordings in Purkinje cells from a defined area in parasaggital
      slices of cerebellar lobule HVI, obtained after rabbits were given either paired
      (classical conditioning) or explicitly unpaired (control) presentations of tone
      and periorbital electrical stimulation, were used to assess the nature and
      duration of conditioning-specific changes in Purkinje cell dendritic membrane
      excitability. We found a strong relationship between the level of conditioning
      and Purkinje cell dendritic membrane excitability after initial acquisition of
      the conditioned response. Moreover, conditioning-specific increases in Purkinje
      cell excitability were still present 1 month after classical conditioning.
      Although dendritically recorded membrane potential, input resistance, and
      amplitude of somatic and dendritic spikes were not different in cells from paired
      or control animals, the size of a potassium channel-mediated transient
      hyperpolarization was significantly smaller in cells from animals that received
      classical conditioning. In slices of lobule HVI obtained from naive rabbits, the
      conditioning-related increases in membrane excitability could be mimicked by
      application of potassium channel antagonist tetraethylammonium chloride,
      iberiotoxin, or 4-aminopyridine. However, only 4-aminopyridine was able to reduce
      the transient hyperpolarization. The pharmacological data suggest a role for
      potassium channels and, possibly, channels mediating an IA-like current, in
      learning-specific changes in membrane excitability. The conditioning-specific
      increase in Purkinje cell dendritic excitability produces an
      afterhyperpolarization, which is hypothesized to release the cerebellar deep
      nuclei from inhibition, allowing conditioned responses to be elicited via the red
      nucleus and accessory abducens motorneurons.

PMID- 9651231
TI  - Mice lacking ataxin-1 display learning deficits and decreased hippocampal paired
      pulse facilitation.
AB  - Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disorder
      characterized by ataxia, progressive motor deterioration, and loss of cerebellar
      Purkinje cells. To investigate SCA1 pathogenesis and to gain insight into the
      function of the SCA1 gene product ataxin-1, a novel protein without homology to
      previously described proteins, we generated mice with a targeted deletion in the
      murine Sca1 gene. Mice lacking ataxin-1 are viable, fertile, and do not show any
      evidence of ataxia or neurodegeneration. However, Sca1 null mice demonstrate
      decreased exploratory behavior, pronounced deficits in the spatial version of the
      Morris water maze test, and impaired performance on the rotating rod apparatus.
      Furthermore, neurophysiological studies performed in area CA1 of the hippocampus
      reveal decreased paired-pulse facilitation in Sca1 null mice, whereas long-term
      and post-tetanic potentiations are normal. These findings demonstrate that SCA1
      is not caused by loss of function of ataxin-1 and point to the possible role of
      ataxin-1 in learning and memory.

PMID- 9651232
TI  - Glutamate receptor targeting to synaptic populations on Purkinje cells is
      developmentally regulated.
AB  - Selective targeting of neurotransmitter receptors to specific synapse populations
      occurs in adult neurons, but little is known about the development of these
      receptor distribution patterns. In this study, we demonstrate that a specific
      developmental switch occurs in the targeting of a receptor to an identified
      synapse population. Localization of delta and AMPA glutamate receptors at
      parallel and climbing fiber synapses on the developing Purkinje cells was studied
      using postembedding immunogold. Delta receptors were found to be abundant on
      postsynaptic membranes at parallel fiber synapses from postnatal day 10 (P10) to
      adult. In contrast, delta receptors were found to be high at climbing fiber
      synapses only at P10 and P14. Thus, a major finding of this paper is that high
      levels of delta receptors are transiently expressed in climbing fiber synapses in
      the second postnatal week. Labeling of synapses with anti-delta receptor antibody
      at P10 was limited to the postsynaptic membrane of excitatory synapses and was
      absent from GABAergic synapses. Unlike delta receptor immunolabeling, AMPA
      receptor immunolabeling (GluR2/3 and GluR2 antibodies) was high in the
      postsynaptic membranes of synapses at early postnatal ages (P2 and P5) and was
      higher in climbing fiber synapses than in parallel fiber synapses from P10 to
      adult. The present study shows that synapse-specific targeting of glutamate
      receptors in Purkinje cells is developmentally regulated, with the postsynaptic
      receptor composition established during synapse maturation. This composition is
      not dependent on the nature of the initial establishment of synaptic connections.

PMID- 9651233
TI  - The role of corticotropin-releasing factor and corticosterone in stress- and
      cocaine-induced relapse to cocaine seeking in rats.
AB  - We have shown previously that footshock stress and priming injections of cocaine
      reinstate cocaine seeking in rats after prolonged drug-free periods (Erb et al.,
      1996). Here we examined the role of brain corticotropin-releasing factor (CRF)
      and the adrenal hormone corticosterone in stress- and cocaine-induced
      reinstatement of cocaine seeking in rats. The ability of footshock stress and
      priming injections of cocaine to induce relapse to cocaine seeking was studied
      after intracerebroventricular infusions of the CRF receptor antagonist D-Phe
      CRF12-41, after adrenalectomy, and after adrenalectomy with corticosterone
      replacement. Rats were allowed to self-administer cocaine (1.0 mg/kg/infusion,
      i.v) for 3 hr daily for 10-14 d and were then placed on an extinction schedule
      during which saline was substituted for cocaine. Tests for reinstatement were
      given after intermittent footshock (10 min; 0.5 mA) and after priming injections
      of saline and cocaine (20 mg/kg, i.p.). Footshock reinstated cocaine seeking in
      both intact animals and animals with corticosterone replacement but not in
      adrenalectomized animals. The CRF receptor antagonist D-Phe CRF12-41 blocked
      footshock-induced reinstatement at all doses tested in both intact animals and
      animals with corticosterone replacement. Reinstatement by priming injections of
      cocaine was only minimally attenuated by adrenalectomy and by pretreatment with D
      Phe CRF12-41. These data suggest that brain CRF plays a critical role in stress
      induced, but only a modulatory role in cocaine-induced, reinstatement of cocaine
      seeking. Furthermore, the data show that although reinstatement of cocaine
      seeking by footshock stress requires minimal, basal, levels of corticosterone,
      stress-induced increases in corticosterone do not play a role in this effect.

PMID- 9651234
TI  - Absence of fenfluramine-induced anorexia and reduced c-Fos induction in the
      hypothalamus and central amygdaloid complex of serotonin 1B receptor knock-out
      mice.
AB  - Fenfluramine, a serotonin releaser and uptake inhibitor, has been widely
      prescribed as an appetite suppressant. Despite its popular clinical use, however,
      the precise neural pathways and specific 5-HT receptors that account for its
      anorectic effect have yet to be elucidated. To test the hypothesis that
      stimulation of 5-HT1B receptors is required for the anorectic effect of
      fenfluramine, we assessed food intake in wild-type and 5-HT1B knock-out mice.
      Next, to determine possible brain structures and pathways that may contribute to
      the 5-HT1B-mediated effects of fenfluramine, we studied by immunohistochemistry
      the induction of the immediate early gene c-fos. Although the effect of
      fenfluramine on locomotion was indistinguishable between both wild-type and 5
      HT1B knock-out mice, the anorectic effect of the drug was absent in only the
      knock-out mice. Furthermore, the induction of c-Fos immunoreactivity found in the
      paraventricular nucleus of the hypothalamus (PVN) of wild-type mice was
      substantially reduced in the knock-outs. Induction in the central amygdaloid
      nucleus (CeA) and in the bed nucleus of the stria terminalis (BNST), although
      robust in wild-type animals, was completely absent in knock-out animals. The
      mixed 5-HT1A/1B agonist RU24969 was able to mimic both the hypophagia and c-fos
      induction elicited by fenfluramine in wild-type mice, but not in the 5-HT1B knock
      out mice. Our results thus demonstrate that stimulation of 5-HT1B receptors is
      required for fenfluramine-induced anorexia and suggest a role for the PVN, CeA,
      and BNST in mediating this effect.

PMID- 9651235
TI  - Corticolimbic dopamine neurotransmission is temporally dissociated from the
      cognitive and locomotor effects of phencyclidine.
AB  - The behavioral syndrome produced by phencyclidine (PCP) and its analog ketamine
      represents a pharmacological model for some aspects of schizophrenia. Despite the
      multifaceted properties of these drugs, the main mechanism for their
      psychotomimetic and cognitive-impairing effects has been thought heretofore to
      involve the corticolimbic dopamine system. The present study examined the
      temporal relationship between alterations in corticolimbic dopamine and glutamate
      neurotransmission and two dopamine-dependent behavioral effects of PCP in the
      rodent that have relevance to the clinical phenomenology, namely, impairment of
      working memory, which is used to model the frontal lobe deficits associated with
      schizophrenia, and hyperlocomotion, which is used as a predictor of the
      propensity of a drug to elicit or exacerbate psychosis. PCP increased dopamine
      and glutamate efflux in the prefrontal cortex and nucleus accumbens, as measured
      by microdialysis. The increase in dopamine in both regions remained elevated well
      above baseline 2.5 hr after the injection, at which time the experiment was
      terminated. However, locomotor activity returned to baseline in <2 hr after
      injection. Furthermore, impaired performance in a discrete trial delayed
      alternation task, a rodent working memory task, was only evident up to 60 min
      after PCP injection; animals tested 80 min after injection, when cortical
      dopamine release was elevated at 300% of baseline, did not exhibit impaired
      performance. These findings indicate that activation of dopamine
      neurotransmission is not sufficient to sustain PCP-induced locomotion and
      impairment of working memory. Thus, effects of PCP, including a glutamatergic
      hyperstimulation, may be necessary to account for the psychotomimetic and
      cognitive-impairing effects of this drug.

PMID- 9651236
TI  - Quality of life for individuals with traumatic brain injury: comparison with
      others living in the community.
AB  - OBJECTIVES: To provide a conceptual overview of approaches to quality of life
      (QOL) measurement and an extensive review of research relating to QOL after TBI;
      to document subjective QOL of individuals with traumatic brain injury (TBI); to
      explore how subjective QOL differs for people with TBI in comparison to
      individuals with no disability (ND) and those with spinal cord injury (SCI); and
      to document the perceptions of unmet important needs and the relationship between
      such perceptions and subjective QOL. DESIGN: Interview-based data focusing on
      current perceptions of QOL and unmet important needs, obtained from individuals
      with TBI, SCI, or ND. Covariance and partial regression analyses were used to
      explore group differences and to document relationships between variables.
      SETTING: Individuals drawn from diverse communities across New York State.
      PARTICIPANTS: TBI group: 430 individuals who identified themselves as having TBI;
      SCI group: 101 individuals with spinal cord injury; ND group: 187 people who
      identified themselves as having no disability. Participants were recruited
      through recruitment ads in general circulation newspapers and newsletters and
      through contacting a wide variety of community agencies. MAIN OUTCOME MEASURES:
      Two summary QOL indicators: a Global QOL Measure based on two items tapping the
      individual's emotion-based view of QOL, and a summary score adapted from
      Flanagan"s Scale of Needs, reflecting the individual's perceptions of total unmet
      important needs. RESULTS: Both summary QOL indicators were correlated with
      demographic characteristics. Unmet important needs were stronger in the TBI group
      than in the SCI and ND groups. Most areas of unmet important need were moderately
      correlated with the summary QOL indicators. Analyses of covariance showed that
      severity of injury was a more powerful modulator of post-TBI QOL judgments than
      the mere fact of TBI. For example, those with the most severe injury (ie, loss of
      consciousness [LOC] >1 month) rated their QOL similar to that in the ND group,
      whereas individuals who had experienced only a brief LOC (<20 minutes) viewed
      their QOL as significantly lower than that in the ND and SCI groups and lower
      than other TBI severity subgroups. CONCLUSIONS: This exploration of subjective
      QOL strengthens the argument that after TBI, the insider"s reaction to injury
      varies greatly within the population. Thus, severity of injury strongly affects
      perceptions of QOL. The use of a multimethod approach for exploring the reactions
      and perceptions of QOL has proven useful in this study.

PMID- 9651237
TI  - Axis I psychopathology in individuals with traumatic brain injury.
AB  - OBJECTIVES: To assess the incidence, comorbidity, and patterns of resolution of
      DSM-IV mood, anxiety, and substance use disorders in individuals with traumatic
      brain injury (TBI). DESIGN: The Structured Clinical Interview for DSM-IV
      Diagnoses (SCID) was utilized. Diagnoses were determined for three onset points
      relative to TBI onset: pre-TBI, post-TBI, and current diagnosis. Contrasts of
      prevalence rates with community-based samples, as well as chi-square analysis and
      analysis of variance were used. Demographics considered in analyses included
      gender, marital status, severity of injury, and years since TBI onset. SETTING:
      Urban, suburban, and rural New York state. PARTICIPANTS: 100 adults with TBI who
      were between the ages of 18 and 65 years and who were, on average, 8 years post
      onset at time of interview. MAIN OUTCOME MEASURES: SCID Axis I mood diagnoses of
      major depression, dysthymia, and bipolar disorder; anxiety diagnoses of panic
      disorder, obsessive-compulsive disorder (OCD), posttraumatic stress disorder
      (PTSD), generalized anxiety disorder (GAD), and phobia; and substance use
      disorders. RESULTS: Prior to TBI, a significant percentage of individuals
      presented with substance use disorders. After TBI, the most frequent Axis I
      diagnoses were major depression and select anxiety disorders (ie, PTSD, OCD, and
      panic disorder). Comorbidity was high, with 44% of individuals presenting with
      two or more Axis I diagnoses post TBI. Individuals without a pre-TBI Axis I
      disorder were more likely to develop post-TBI major depression and substance use
      disorders. Rates of resolution were similar for individuals regardless of
      previous psychiatric histories. Major depression and substance use disorders were
      more likely than were anxiety disorders to remit. CONCLUSION: TBI is a risk
      factor for subsequent psychiatric disabilities. The need for proactive
      psychiatric assessment and timely interventions in individuals post TBI is
      indicated.

PMID- 9651238
TI  - The Beck Depression Inventory: is it a suitable measure of depression for
      individuals with traumatic brain injury?
AB  - OBJECTIVE: This study examined the relationship between Beck Depression Inventory
      (BDI) scores and current diagnosis of depression, based on The Structured
      Clinical Interview for DSM-IV Diagnosis (SCID). DESIGN: Correlation. SETTING:
      Community-based sample. PARTICIPANTS: 100 individuals with traumatic brain injury
      (TBI) participated in this study, 25 of whom were diagnosed as depressed and 75
      as not depressed at the time of interview. MAIN OUTCOME MEASURES: BDI scores,
      number of symptoms reported on a symptom checklist and DSM-IV diagnosis of
      depression. RESULTS: BDI symptoms correlated significantly with the SCID
      diagnosis of depression (r = .30) but were more strongly related (r = .67) to the
      number of non-depression-related problems reported, using the TIRR Symptom
      Checklist, a list of symptoms frequently found post TBI. The BDI had low
      sensitivity for discriminating depressed from nondepressed individuals
      (sensitivity = 36% when specificity was set at 80%). These results suggest that
      for individuals with TBI, high BDI scores may reflect hyperreactivity to post-TBI
      symptoms to a greater extent than clinical depression. CONCLUSIONS: Further study
      is needed to (1) understand the physiological, functional, and psychosocial
      factors that are associated with depression in individuals with TBI; (2) provide
      the basis for developing better measures of depression; and (3) understand how
      depression is experienced after TBI.

PMID- 9651239
TI  - Undiagnosed health issues in individuals with traumatic brain injury living in
      the community.
AB  - OBJECTIVES: To examine the self-reported prevalence of long-term health issues in
      individuals with traumatic brain injury (TBI) living in the community. DESIGN: A
      structured health interview. For individuals with TBI, the presence of a specific
      health-related issue with onset post-TBI and currently a problem at the time of
      the interview was explored. For individuals without disability, a specific health
      related issue was evaluated at time of interview. For each health issue, the
      proportion of individuals with TBI experiencing post-TBI onset but current
      symptoms was contrasted with symptom reports of individuals without disability.
      Chi-square statistical analyses were used to determine significance. For
      individuals with TBI, logistic regressions were used to model the probability of
      having a particular health difficulty when four covariates were examined, such as
      age, gender, time since onset of TBI, and duration of loss of consciousness
      (LOC). SETTING: Urban, suburban, and rural New York State. PARTICIPANTS: 338
      individuals with TBI and 273 individuals without disability between the ages of
      18 and 65 years. Individuals with TBI were, on average, 10 years post-onset at
      the time of interview. MAIN OUTCOME MEASURES: Self-reported health issues
      reflective of neuroendocrine, neurological, immunosuppression, and other health
      issues. RESULTS: Chronic health issues suggestive of ongoing neuroendocrine
      dysfunctions (ie, changes in hair/skin texture, body temperature changes),
      neurologic difficulties (ie, headaches, seizures, balance difficulties,
      spasticity, sleep disturbances, loss of urinary control), and arthritic
      complaints were significantly more common in individuals with TBI. The prevalence
      of many of these health-related difficulties was related to duration of LOC but
      not to time since injury. Age and gender effects were found, with older women
      with TBI more likely to report thyroid conditions, sleep disturbances, loss of
      urinary control, and arthritic changes. Women also reported greater frequency of
      headaches, colds, weight changes, and temperature changes post TBI. CONCLUSION:
      Health issues reflective of neuroendocrine, neurological, and arthritic
      difficulties are common long-term health issues for individuals with TBI.
      Proactive patient education, ongoing health screening with appropriate medical
      follow-up, and timely interventions for individuals with TBI are indicated.
      Longitudinal studies are necessary to examine the natural course of post-TBI
      health difficulties.

PMID- 9651240
TI  - The benefits of exercise in individuals with traumatic brain injury: a
      retrospective study.
AB  - OBJECTIVE: This study examined the benefits of exercise. DESIGN: A retrospective
      study. SETTING: A community-based sample. PARTICIPANTS: A sample of 240
      individuals with traumatic brain injury (TBI) (64 exercisers and 176
      nonexercisers) and 139 individuals without a disability (66 exercisers and 73
      nonexercisers). MAIN OUTCOME MEASURES: Scales measuring disability and handicap.
      RESULTS: It was found that the TBI exercisers were less depressed than
      nonexercising individuals with TBI, TBI exercisers reported fewer symptoms, and
      their self-reported health status was better than the nonexercising individuals
      with TBI. There were no differences between the two groups of individuals with
      TBI on measures of disability and handicap. CONCLUSIONS: The findings suggest
      that exercise improves mood and aspects of health status but does affect aspects
      of disability and handicap.

PMID- 9651241
TI  - The effect of employment on quality of life and community integration after
      traumatic brain injury.
AB  - OBJECTIVES: To investigate the effect of employment on perceived quality of life
      (QOL), social integration, and home and leisure activities for individuals with
      traumatic brain injuries (TBIs). DESIGN: A number of demographic and injury
      related variables (age at injury, time since injury, severity of injury,
      education, gender, preinjury household income, and marital status) were analyzed
      for their association first with employment and then with the QOL, social
      integration, and home and leisure activities. Any of these variables showing
      significant associations were then included along with level of employment in
      three final multivariate analyses of variance (MANOVAs), again predicting QOL,
      social integration, and home and leisure activities. SETTING: Urban, suburban,
      and rural New York state. PARTICIPANTS: 337 adults with TBI who resided in New
      York state and were between the ages of 18 and 65 years. MAIN OUTCOME MEASURES:
      The Craig Handicap Assessment Capacity Technique, the Bigelow Quality of Life
      Questionnaire, the Flanagan Scale of Needs (adapted), and a global QOL measure.
      RESULTS: Employment showed a strong and consistent relationship with perceived
      QOL, social integration within the community, and home and leisure activities.
      Part-time employment may have been superior to full-time employment for
      individuals with TBI: part-time workers had fewer unmet needs, were more socially
      integrated, and were more engaged in home activities than full-time workers. Loss
      of consciousness, as a measure of severity, was unexpectedly predictive of
      diminished sense of QOL for individuals with less severe injuries. CONCLUSIONS:
      Being employed contributes to one"s sense of well-being, social integration, and
      pursuit of leisure and home activities. Select advantages of working part-time
      for individuals with TBI were identified.

PMID- 9651242
TI  - Reproductive dominance of pasture trees in a fragmented tropical forest mosaic 
AB  - Tropical forest fragmentation threatens biodiversity, yet basic information on
      population responses for major groups such as plants is lacking. Hypervariable
      genetic markers were used to reconstruct a population-level pedigree in
      fragmented tropical forest for the tree Symphonia globulifera. Though seedlings
      occurred only in remnant forest, the pedigree showed that most seedlings had been
      produced by sequentially fewer adults in pasture, creating a genetic bottleneck.
      The pedigree also implicated shifts in the foraging of animals that disperse
      pollen and seed in a secondary constriction of the bottleneck. These results
      suggest that tropical conservation strategies should anticipate complex, cryptic
      responses to fragmentation.

PMID- 9651243
TI  - Interaction of human Arp2/3 complex and the Listeria monocytogenes ActA protein
      in actin filament nucleation.
AB  - Actin filament assembly at the cell surface of the pathogenic bacterium Listeria
      monocytogenes requires the bacterial ActA surface protein and the host cell
      Arp2/3 complex. Purified Arp2/3 complex accelerated the nucleation of actin
      polymerization in vitro, but pure ActA had no effect. However, when combined, the
      Arp2/3 complex and ActA synergistically stimulated the nucleation of actin
      filaments. This mechanism of activating the host Arp2/3 complex at the L.
      monocytogenes surface may be similar to the strategy used by cells to control
      Arp2/3 complex activity and hence the spatial and temporal distribution of actin
      polymerization.

PMID- 9651244
TI  - Congenital heart disease caused by mutations in the transcription factor NKX2-5.
AB  - Mutations in the gene encoding the homeobox transcription factor NKX2-5 were
      found to cause nonsyndromic, human congenital heart disease. A dominant disease
      locus associated with cardiac malformations and atrioventricular conduction
      abnormalities was mapped to chromosome 5q35, where NKX2-5, a Drosophila tinman
      homolog, is located. Three different NKX2-5 mutations were identified. Two are
      predicted to impair binding of NKX2-5 to target DNA, resulting in
      haploinsufficiency, and a third potentially augments target-DNA binding. These
      data indicate that NKX2-5 is important for regulation of septation during cardiac
      morphogenesis and for maturation and maintenance of atrioventricular node
      function throughout life.

PMID- 9651246
TI  - 7500 years of prehistoric footwear from arnold research cave, missouri 
AB  - Accelerator mass spectrometer dating of an assemblage of fibrous and leather
      footwear from Arnold Research Cave in central Missouri documents a long sequence
      of shoe construction by prehistoric Midwestern peoples, beginning perhaps as
      early as 8300 calendar years before the present (cal years B.P.). An earlier
      fibrous sandal form dates from 8325 to 7675 cal years B.P., and later fibrous or
      leather slip-ons span the period from 5575 to 1070 cal years B.P. The assemblage
      adds to a growing picture of the highly varied nature of prehistoric footwear
      production in the United States throughout the Holocene.

PMID- 9651245
TI  - Complete structure of the 11-subunit bovine mitochondrial cytochrome bc1 complex.
AB  - Mitochondrial cytochrome bc1 complex performs two functions: It is a respiratory
      multienzyme complex and it recognizes a mitochondrial targeting presequence.
      Refined crystal structures of the 11-subunit bc1 complex from bovine heart reveal
      full views of this bifunctional enzyme. The "Rieske" iron-sulfur protein subunit
      shows significant conformational changes in different crystal forms, suggesting a
      new electron transport mechanism of the enzyme. The mitochondrial targeting
      presequence of the "Rieske" protein (subunit 9) is lodged between the two "core"
      subunits at the matrix side of the complex. These "core" subunits are related to
      the matrix processing peptidase, and the structure unveils how mitochondrial
      targeting presequences are recognized.

PMID- 9651247
TI  - Dissociative recombination of HD+ in selected vibrational quantum states 
AB  - Rate coefficients for dissociative recombination of HD+ in selected vibrational
      states have been measured by a combination of two molecular fragment imaging
      methods by using the heavy-ion storage ring technique. Recombination fragment
      imaging yields state-to-state reaction rates. These rates are converted to rate
      coefficients by using vibrational level populations of the stored ion beam,
      derived from nuclear coordinate distributions measured on extracted ions. The
      results show strongly increasing rate coefficients for high vibrational
      excitation, where additional dissociation routes open up, in agreement with a
      theoretical calculation. Very low rate coefficients are found for certain,
      isolated vibrational states.

PMID- 9651248
TI  - An inverted hexagonal phase of cationic liposome-DNA complexes related to DNA
      release and delivery.
AB  - A two-dimensional columnar phase in mixtures of DNA complexed with cationic
      liposomes has been found in the lipid composition regime known to be
      significantly more efficient at transfecting mammalian cells in culture compared
      to the lamellar (LalphaC) structure of cationic liposome-DNA complexes. The
      structure, derived from synchrotron x-ray diffraction, consists of DNA coated by
      cationic lipid monolayers and arranged on a two-dimensional hexagonal lattice
      (HIIC). Two membrane-altering pathways induce the LalphaC --> HIIC transition:
      one where the spontaneous curvature of the lipid monolayer is driven negative,
      and another where the membrane bending rigidity is lowered with a new class of
      helper-lipids. Optical microscopy revealed that the LalphaC complexes bind stably
      to anionic vesicles (models of cellular membranes), whereas the more transfectant
      HIIC complexes are unstable and rapidly fuse and release DNA upon adhering to
      anionic vesicles.

PMID- 9651249
TI  - Pleistocene collapse of the west antarctic ice sheet 
AB  - Some glacial sediment samples recovered from beneath the West Antarctic ice sheet
      at ice stream B contain Quaternary diatoms and up to 10(8) atoms of beryllium-10
      per gram. Other samples contain no Quaternary diatoms and only background levels
      of beryllium-10 (less than 10(6) atoms per gram). The occurrence of young diatoms
      and high concentrations of beryllium-10 beneath grounded ice indicates that the
      Ross Embayment was an open marine environment after a late Pleistocene collapse
      of the marine ice sheet.

PMID- 9651250
TI  - Effects of water on the alpha-beta transformation kinetics in san carlos olivine 
AB  - In experiments at 13.5 gigapascals and 1030 degreesC, the growth rate of
      wadsleyite, which forms from transformation of olivine, was substantially
      enhanced by the presence of water. Wadsleyite had a low dislocation density and
      subgrain boundaries in wet runs. Water enhanced the dislocation recovery in
      wadsleyite and therefore caused inelastic relaxation of the localized pressure
      drop associated with the transformation, resulting in an increase of the growth
      rate in wet runs. These results imply that even a small amount of water of 0. 05
      weight percent can weaken wadsleyite in the mantle.

PMID- 9651251
TI  - High-temperature silicate volcanism on Jupiter's moon Io.
AB  - Infrared wavelength observations of Io by the Galileo spacecraft show that at
      least 12 different vents are erupting lavas that are probably hotter than the
      highest temperature basaltic eruptions on Earth today. In at least one case, the
      eruption near Pillan Patera, two independent instruments on Galileo show that the
      lava temperature must have exceeded 1700 kelvin and may have reached 2000 kelvin.
      The most likely explanation is that these lavas are ultramafic (magnesium-rich)
      silicates, and this idea is supported by the tentative identification of
      magnesium-rich orthopyroxene in lava flows associated with these high-temperature
      hot spots.

PMID- 9651252
TI  - Mixer, a homeobox gene required for endoderm development.
AB  - An expression cloning strategy in Xenopus laevis was used to isolate a homeobox
      containing gene, Mixer, that can cause embryonic cells to form endoderm. Mixer
      transcripts are found specifically in the prospective endoderm of gastrula, which
      coincides with the time and place that endodermal cells become histologically
      distinct and irreversibly determined. Loss-of-function studies with a dominant
      inhibitory mutant demonstrate that Mixer activity is required for endoderm
      development. In particular, the expression of Sox17alpha and Sox17beta, two
      previously identified endodermal determinants, require Mixer function. Together,
      these data suggest that Mixer is an embryonic transcription factor involved in
      specifying the endodermal germ layer.

PMID- 9651253
TI  - Visualization of specific B and T lymphocyte interactions in the lymph node.
AB  - Early events in the humoral immune response were visualized in lymph nodes by
      simultaneous tracking of antigen-specific CD4 T and B cells after immunization.
      The T cells were initially activated in the T cell areas when the B cells were
      still randomly dispersed in the B cell-rich follicles. Both populations then
      migrated to the edges of the follicles and interacted there, resulting in CD154
      dependent B cell proliferation and germinal center formation. These results
      provide visual documentation of cognate T-B cell interactions and localize them
      to the follicular border.

PMID- 9651255
TI  - Our feet set on a new path entirely. To the transformation of primary care and
      partnership with patients.

PMID- 9651256
TI  - The jewel in welfare's crown. The NHS will glisten still if it retains middle
      class support.

PMID- 9651254
TI  - C1 transfer enzymes and coenzymes linking methylotrophic bacteria and
      methanogenic Archaea.
AB  - Methanogenic and sulfate-reducing Archaea are considered to have an energy
      metabolism involving C1 transfer coenzymes and enzymes unique for this group of
      strictly anaerobic microorganisms. An aerobic methylotrophic bacterium,
      Methylobacterium extorquens AM1, was found to contain a cluster of genes that are
      predicted to encode some of these enzymes and was shown to contain two of the
      enzyme activities and one of the methanogenic coenzymes. Insertion mutants were
      all unable to grow on C1 compounds, suggesting that the archaeal enzymes function
      in aerobic C1 metabolism. Thus, methylotrophy and methanogenesis involve common
      genes that cross the bacterial/archaeal boundaries.

PMID- 9651257
TI  - Imagining futures for the NHS. Familiar institutions might be revamped and
      strong.

PMID- 9651258
TI  - On the way to Calvary. Ministers should realise the command and control model the
      white paper entails.

PMID- 9651259
TI  - Getting evidence into practice. Needs the right resources and the right
      organisation.

PMID- 9651260
TI  - Randomised trial of heroin maintenance programme for addicts who fail in
      conventional drug treatments.
AB  - OBJECTIVE: To evaluate an experimental heroin maintenance programme. DESIGN:
      Randomised trial. SETTING: Outpatient clinic in Geneva, Switzerland. SUBJECTS:
      Heroin addicts recruited from the community who were socially marginalised and in
      poor health and had failed in at least two previous drug treatments.
      INTERVENTION: Patients in the experimental programme (n=27) received intravenous
      heroin and other health and psychosocial services. Control patients (n=24)
      received any other conventional drug treatment (usually methadone maintenance).
      MAIN OUTCOME MEASURES: Self reported drug use, health status (SF-36), and social
      functioning. RESULTS: 25 experimental patients completed 6 months in the
      programme, receiving a median of 480 mg of heroin daily. One experimental subject
      and 10 control subjects still used street heroin daily at follow up (difference
      44%; 95% confidence interval 16% to 71%). Health status scores that improved
      significantly more in experimental subjects were mental health (0.58 SD; 0.07 to
      1.10), role limitations due to emotional problems (0.95 SD; 0.11 to 1.79), and
      social functioning (0.65 SD; 0.03 to 1.26). Experimental subjects also
      significantly reduced their illegal income and drug expenses and committed fewer
      drug and property related offences. There were no benefits in terms of work,
      housing situation, somatic health status, and use of other drugs. Unexpectedly,
      only nine (38%) control subjects entered the heroin maintenance programme at
      follow up. CONCLUSIONS: A heroin maintenance programme is a feasible and
      clinically effective treatment for heroin users who fail in conventional drug
      treatment programmes. Even in this population, however, another attempt at
      methadone maintenance may be successful and help the patient to stop using
      injectable opioids.

PMID- 9651261
TI  - Malignant spinal cord compression: prospective study of delays in referral and
      treatment.
AB  - OBJECTIVES: To examine the delay in presentation, diagnosis, and treatment of
      malignant spinal cord compression and to define the effect of this delay on motor
      and bladder function at the time of treatment. DESIGN: Prospective study of all
      new patients presenting to a regional cancer centre with this condition. SETTING:
      Regional cancer centre. SUBJECTS: 301 consecutive patients. MAIN OUTCOME
      MEASURES: Interval from onset of symptoms to presentation and treatment, delay at
      each stage of referral, and functional deterioration. RESULTS: The median (range)
      delay from onset of symptoms of spinal cord compression to treatment was 14 (0
      840) days. Of the total delay, 3 (0-300) days were accounted for by patients, 3
      (0-330) days by general practitioners, 4 (0-794) days by the district general
      hospital, and 0 (0-114) days by the treatment unit. Initial presentation to the
      regional cancer centre with symptoms of malignant spinal cord compression led to
      a significant reduction in delay to treatment and improved functional status at
      the time of treatment. Deterioration of motor or bladder function >=1 grade
      occurred at the general practice stage in 28% (57) and 18% (36) of patients, the
      general hospital stage in 36% (83) and 29% (66), and the treatment unit stage in
      6% (19) and 5% (15), respectively. CONCLUSIONS: Unacceptable delay in diagnosis,
      investigation, and referral occurs in most patients with malignant spinal cord
      compression and results in preventable loss of function before treatment.
      Improvement in the outcome of such patients requires earlier diagnosis and
      treatment.

PMID- 9651262
TI  - Reactions of participants to the results of a randomised controlled trial:
      exploratory study.
AB  - OBJECTIVES: To assess views of parents of babies who participated in a neonatal
      trial, about feedback of trial results. DESIGN: Qualitative analysis of
      interviews. SETTING: Parents' homes. SUBJECTS: Parents of 24 surviving babies
      enrolled in a UK randomised controlled trial comparing ventilatory support by
      extracorporeal membrane oxygenation with conventional management. MAIN OUTCOME
      MEASURES: Views about contents of results, reactions to results, effect of
      hindsight, and importance of feedback. RESULTS: Information about mortality was
      well understood by the parents but morbidity was less clearly reported. Even when
      the content was emotionally exacting, the information was still wanted as it
      removed uncertainty; provided an endpoint to difficult events; promoted further
      discussion within couples; and acknowledged their contribution to answering an
      important clinical question. CONCLUSIONS: Feedback of trial results to
      participants should be a consideration of researchers, but a careful approach is
      required. This study was based on a highly selective group of parents within a
      particularly sensitive trial. More research is needed to assess the extent to
      which these results can be generalised to other trials or to groups such as
      bereaved parents.

PMID- 9651263
TI  - Efficacy of home sampling for screening of Chlamydia trachomatis: randomised
      study.

PMID- 9651265
TI  - It pays to be a native 

PMID- 9651264
TI  - It pays to be a native 

PMID- 9651267
TI  - Feet on the ground 

PMID- 9651266
TI  - Influence of social problems on management in general practice: multipractice
      questionnaire survey.
AB  - OBJECTIVES: To find how often social problems influence clinical management in
      general practice, how management is changed, and how the characteristics of
      patients, doctors, and the doctor-patient relationship influence this management.
      DESIGN: Multipractice survey of patients consulting general practitioners.
      Doctors completed a questionnaire for each patient. SETTING: General practices in
      Buskerud county, Norway. SUBJECTS: 1401 consecutive adult patients attending 89
      general practitioners. MAIN OUTCOME MEASURES: How often management of patients
      was influenced by different types of social problem and main reasons for
      consultation; frequency and intercorrelation of different types of management
      applied; odds ratios for social problems' influence on management, controlled for
      by characteristics of doctors, patients, and their relationship. RESULTS: In 17%
      of all consultations the doctors' knowledge of patients' social problems
      influenced their management, stressful working conditions being the most frequent
      influencing type of problem. Knowledge of social problems influenced management
      more often when the doctor knew a patient well, but less often the longer a
      doctor had worked in a practice. When social problems influenced management, the
      commonest types of management offered were extra time for consultation (51%),
      advice (42%), authorisation of sick leave (28%), and prescription of a
      psychotropic drug (20%), while referral to community services was used in 2.6% of
      these consultations. Prescription of a psychotropic drug was positively
      correlated with use of extra time, and was made more often by female doctors.
      CONCLUSIONS: Patients' social problems influenced choice of management in at
      least a sixth of consultations. Prior knowledge of the patient, the doctor's time
      in present practice, age and sex of the patient, and sex of the doctor
      significantly influenced management of patients.

PMID- 9651268
TI  - Treatment of the common cold.

PMID- 9651269
TI  - The NHS's 50 anniversary. Something to celebrate. The Bevan legacy.

PMID- 9651270
TI  - The NHS's 50 anniversary. Something to celebrate. As I recall.

PMID- 9651271
TI  - The NHS's 50 anniversary. Something to celebrate. The BMA and the NHS.

PMID- 9651272
TI  - The NHS's 50 anniversary. As others see us: views from abroad. A rational
      bureaucracy in a civilised society.

PMID- 9651273
TI  - The NHS's 50 anniversary. As others see us: views from abroad. A great leap for
      humankind?

PMID- 9651274
TI  - The NHS's 50 anniversary. As others see us: views from abroad. The importance of
      social context.

PMID- 9651275
TI  - The NHS's 50 anniversary. As others see us: views from abroad. Justice and health
      care in a caring society.

PMID- 9651276
TI  - The NHS's 50 anniversary. As others see us: views from abroad. A social
      experiment that keeps adapting.

PMID- 9651277
TI  - The NHS's 50 anniversary. Looking forward. The NHS: feeling well and thriving at
      75.

PMID- 9651278
TI  - The NHS's 50 anniversary. Clinical governance and the drive for quality
      improvement in the new NHS in England.

PMID- 9651279
TI  - The NHS's 50 anniversary. Will the fudge on equity sustain the NHS into the next
      millennium?

PMID- 9651280
TI  - The NHS's 50 anniversary. Change and resistance to change in the NHS.

PMID- 9651281
TI  - Making better use of research findings.

PMID- 9651282
TI  - The new NHS: message to the medical profession from the minister of health 

PMID- 9651283
TI  - Hypertension treatment and control in Sub-saharan Africa. Figure of $1800 per
      life saved seems optimistic.

PMID- 9651284
TI  - Ion channels. Ion specificity of motor end plate acetylcholine receptor.

PMID- 9651285
TI  - Mistaken subdural cannulation can produce Horner's syndrome.

PMID- 9651286
TI  - Incorporating patient preferences into clinical trials. Information about
      patients' preference must be obtained first.

PMID- 9651287
TI  - Potential biases do not affect results of waiting time study.

PMID- 9651288
TI  - Temporary pacing before permanent pacing should be avoided unless essential.

PMID- 9651289
TI  - People at risk of coronary heart disease should not be denied treatment with
      effective drugs for purely financial reasons.

PMID- 9651290
TI  - Dilemmas exist in withdrawing ventilation from dying children.

PMID- 9651291
TI  - Prescribing patient information leaflets may be better than prescribing drugs.

PMID- 9651292
TI  - Substitution of another opioid for morphine. Opioid toxicity should be managed
      initially by decreasing the opioid dose.

PMID- 9651294
TI  - Genetic counselling must be non-directive.

PMID- 9651293
TI  - Consideration of short term consequences of heavier babies is important.

PMID- 9651295
TI  - Private practice should mirror the NHS. Fee structure for anaesthetists in
      private practice needs overhaul.

PMID- 9651297
TI  - George hebbington field 

PMID- 9651296
TI  - Only minority of doctors supported idea of state funded health service in 1945.

PMID- 9651298
TI  - Local medical committee conference 

PMID- 9651299
TI  - Audit in auchendreich 

PMID- 9651300
TI  - Cancer screening-how can we do better? 

PMID- 9651301
TI  - Protean elephants 

PMID- 9651302
TI  - Protean elephants 

PMID- 9651304
TI  - Delays occur in referring and treating malignant spinal cord compression 

PMID- 9651303
TI  - Severely addicted heroin users benefit from heroin maintenance programme 

PMID- 9651305
TI  - Parents involved in research welcome hearing the results 

PMID- 9651306
TI  - GPs management decisions are influenced by patients' social problems in 17% of
      consultations 

PMID- 9651307
TI  - Adapt and survive: the NHS at 50 

PMID- 9651308
TI  - G protein-coupled receptors minireview series.

PMID- 9651309
TI  - G protein-coupled receptors. I. Diversity of receptor-ligand interactions.

PMID- 9651310
TI  - Differential regulation of p53-dependent and -independent proliferating cell
      nuclear antigen gene transcription by 12 S E1A oncoprotein requires CBP.
AB  - The tumor suppressor protein p53 and the adenoviral 12 S E1A oncoprotein are both
      known to elicit their biological effects mainly by regulating the transcription
      of important cellular genes. The human proliferating cell nuclear antigen (PCNA)
      gene is a transcriptional target of both p53 and E1A. We have analyzed the
      effects of p53 and 12 S E1A, separately as well as together, on PCNA gene
      transcription. Our results showed that whereas both p53 and 12 S E1A separately
      activated PCNA transcription, 12 S E1A repressed p53-mediated transcriptional
      activation. Thus, 12 S E1A uses a dual strategy of transcriptional activation and
      repression to take control of the cellular PCNA gene regulation. The cyclic AMP
      response element in the PCNA core promoter, besides being crucial for basal
      transcription, synergizes with p53 to activate transcription. The cyclic AMP
      response element-binding protein (CREB)-binding protein (CBP) is an essential
      component of both the transcriptional activation and repression by E1A. Our data
      demonstrate for the first time that E1A can modulate CBP function to activate
      PCNA transcription, while at the same time repressing p53-mediated activation by
      disrupting CBP interaction with p53, thereby uncoupling PCNA transcription from
      the regulatory effects of p53.

PMID- 9651311
TI  - Regulation of Bcl-xl channel activity by calcium.
AB  - Recent studies have demonstrated that the anti-apoptotic proteins, Bcl-2 and Bcl
      xl, with the carboxyl-terminal hydrophobic domain removed, form cation-selective
      channels in the lipid bilayer reconstitution system. However, the regulatory
      properties of these channels are unknown. In this study, we investigated the ion
      conducting properties of full-length Bcl-xl in the lipid bilayer reconstitution
      system. Our findings indicate that Bcl-xl forms a cation-selective channel that
      conducts sodium but not calcium and that Bcl-xl channel activity is reversibly
      inhibited by luminal calcium with a half-dissociation constant of approximately
      60 microM. This calcium-dependent regulation of the Bcl-xl channel provides new
      insights into the roles of calcium and Bcl-2-related proteins in the programmed
      cell death pathway.

PMID- 9651312
TI  - Constitutive activation of photoreceptor guanylate cyclase by Y99C mutant of GCAP
      1. Possible role in causing human autosomal dominant cone degeneration.
AB  - Photoreceptor membrane guanylate cyclases (RetGC) are regulated by calcium
      binding proteins, GCAP-1 and GCAP-2. At Ca2+ concentrations below 100 nM,
      characteristic of light-adapted photoreceptors, guanylate cyclase-activating
      protein (GCAPs) activate RetGC, and at free Ca2+ concentrations above 500 nM,
      characteristic of dark-adapted photoreceptors, GCAPs inhibit RetGC. A mutation,
      Y99C, in human GCAP-1 was recently found to be linked to autosomal dominant cone
      dystrophy in a British family (Payne, A. M., Downes, S. M., Bessant, D. A. R.,
      Taylor, R., Holder, G. E., Warren, M. J., Bird, A. C., and Bhattachraya, S. S.
      (1998) Hum. Mol. Genet. 7, 273-277). We produced recombinant Y99C GCAP-1 mutant
      and tested its ability to activate RetGC in vitro at various free Ca2+
      concentrations. The Y99C mutation does not decrease the ability of GCAP-1 to
      activate RetGC. However, RetGC stimulated by the Y99C GCAP-1 remains active even
      at Ca2+ concentration above 1 microM. Hence, the cyclase becomes constitutively
      active within the whole physiologically relevant range of free Ca2+
      concentrations. We have also found that the Y99C GCAP-1 can activate RetGC even
      in the presence of Ca2+-loaded nonmutant GCAPs. This is consistent with the fact
      that cone degeneration was dominant in human patients who carried such mutation
      (Payne, A. M., Downes, S. M., Bessant, D. A. R. , Taylor, R., Holder, G. E.,
      Warren, M. J., Bird, A. C., and Bhattachraya, S. S. (1998) Hum. Mol. Genet. 7,
      273-277). A similar mutation, Y104C, in GCAP-2 results in a different phenotype.
      This mutation apparently does not affect Ca2+ sensitivity of GCAP-2. Instead, the
      Y104C GCAP-2 stimulates RetGC less efficiently than the wild-type GCAP-2. Our
      data indicate that cone degeneration associated with the Y99C mutation in GCAP-1
      can be a result of constitutive activation of cGMP synthesis.

PMID- 9651313
TI  - Arachidonic acid activates a proton current in the rat glutamate transporter
      EAAT4.
AB  - The excitatory amino acid transporter EAAT4 is expressed predominantly in
      Purkinje neurons in the rat cerebellum (1-3), and it participates in postsynaptic
      reuptake of glutamate released at the climbing fiber synapse (4). Transporter
      mediated currents in Purkinje neurons are increased more than 3-fold by
      arachidonic acid, a second messenger that is liberated following depolarization
      induced Ca2+ activation of phospholipase A2 (5). In this study we demonstrate
      that application of arachidonic acid to oocytes expressing rat EAAT4 increased
      glutamate-induced currents to a similar extent. However, arachidonic acid did not
      cause an increase in the rate of glutamate transport or in the chloride current
      associated with glutamate transport but rather activated a proton-selective
      conductance. These data reveal a novel action of arachidonate on a glutamate
      transporter and suggest a mechanism by which synaptic activity may decrease
      intracellular pH in neurons where this transporter is localized.

PMID- 9651314
TI  - Three activator protein-1-binding sites bound by the Fra-2.JunD complex cooperate
      for the regulation of murine laminin alpha3A (lama3A) promoter activity by
      transforming growth factor-beta.
AB  - Several lines of evidence suggest a role for laminin-5 in skin wound healing. We
      report here that transforming growth factor-beta (TGF-beta), which elicits
      various responses during cutaneous healing, stimulates transcription of the mouse
      laminin alpha3A (lama3A) gene. To identify the TGF-beta-responsive elements
      (TGFbeta-REs) on the lama3A promoter, we have generated a series of 5'-deletions
      of the promoter upstream of the beta-galactosidase reporter gene. Transient cell
      transfection assays using mouse PAM212 keratinocytes revealed that TGFbeta-REs
      lie between nucleotides -297 and -54 relative to the transcription start site.
      Insertion of the TGFbeta-RE in front of the unresponsive minimal SV40 promoter
      conferred TGF-beta inducibility. Computer analysis of the promoter sequence
      identified three canonical activator protein-1 (AP-1) sites located at
      nucleotides -277 (AP-1A), -125 (AP-1B), and -69 (AP-1C). Site-directed
      mutagenesis of either the AP-1A or AP-1C site did not drastically alter the basal
      activity of the lama3A promoter, but reduced TGF-beta responsiveness by 50%.
      Simultaneous mutation of these two AP-1 sites resulted in a 65% decline in the
      response to TGF-beta, suggesting a cooperative contribution of each site to the
      overall promoter activity. In contrast, mutation of the AP-1B site markedly
      reduced the basal activity of the lama3A promoter, indicating that this AP-1 site
      is essential for gene expression. Mobility shift assays demonstrated specific
      binding of Fra-2 and JunD to the AP-1 sites, suggesting for the first time a
      possible regulatory function for the Fra-2.JunD AP-1 complex in a basal
      keratinocyte-specific gene.

PMID- 9651315
TI  - Identification of protein-protein contacts between alpha/beta-type small, acid
      soluble spore proteins of Bacillus species bound to DNA.
AB  - Small, acid-soluble spore proteins (SASP) of the alpha/beta-type from several
      Bacillus species were cross-linked into homodimers, heterodimers and
      homooligomers with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) in the
      presence of linear plasmid DNA. Significant protein cross-linking was not
      detected in the absence of DNA. In all four alpha/beta-type SASP examined, the
      amino donor in the EDC induced amide cross-links was the alpha-amino group of the
      protein. However, the carboxylate containing amino acid residues involved in
      cross-linking varied. In SASP-A and SASP-C of Bacillus megaterium two conserved
      glutamate residues, which form part of the germination protease recognition
      sequence, were involved in cross-link formation. In SspC from Bacillus subtilis
      and Bce1 from Bacillus cereus the acidic residues involved in cross-link
      formation were not in the protease recognition sequence, but at a site closer to
      the N terminus of the proteins. These data indicate that, although there are
      likely to be subtle structural differences between different alpha/beta-type
      SASP, the N-terminal regions of these proteins are involved in protein-protein
      interactions while in the DNA bound state.

PMID- 9651316
TI  - Functional roles of conserved amino acid residues in DNA methyltransferases
      investigated by site-directed mutagenesis of the EcoRV adenine-N6
      methyltransferase.
AB  - All DNA methyltransferases (MTases) have similar catalytic domains containing
      nine blocks of conserved amino acid residues. We have investigated by site
      directed mutagenesis the function of 17 conserved residues in the EcoRV alpha
      adenine-N6-DNA methyltransferase. The structure of this class of MTases has been
      predicted recently. The variants were characterized with respect to their
      catalytic activities and their abilities to bind to DNA and the S
      adenosylmethionine (AdoMet) cofactor. Amino acids located in motifs X, I, and II
      are shown to be involved in AdoMet binding (Lys16, Glu37, Phe39, and Asp58). Some
      of the mutants defective in AdoMet binding are also impaired in DNA binding,
      suggesting allosteric interactions between the AdoMet and DNA binding site. Asp78
      (motif III), which was supposed to form a hydrogen bond to the AdoMet on the
      basis of the structure predictions, turned out not to be important for AdoMet
      binding, suggesting that motif III has not been identified correctly. R128A and
      N130A, having mutations in the putative DNA binding domain, are unable to bind to
      DNA. Residues located in motifs IV, V, VI, and VIII are involved in catalysis
      (Asp193, Tyr196, Asp211, Ser229, Trp231, and Tyr258), some of them presumably in
      binding the flipped target base, because mutations at these residues fail to
      significantly interfere with DNA and AdoMet binding but strongly reduce
      catalysis. Our results are in substantial agreement with the structure prediction
      for EcoRV alpha-adenine-N6-methyltransferase and x-ray structures of other
      MTases.

PMID- 9651317
TI  - A membrane setting for the sorting motifs present in the adenovirus E3-13.7
      protein which down-regulates the epidermal growth factor receptor.
AB  - The adenovirus E3-13.7 protein interferes with endosomal protein sorting to down
      regulate the epidermal growth factor receptor and related tyrosine kinase
      receptors. The cytoplasmic C terminus of this protein contains three protein
      sorting motifs which are related to the function of E3-13.7. In this study, the
      structure of a 23-residue polypeptide corresponding to this domain was examined
      using solution NMR and CD spectroscopic methods. The peptide was observed to
      exist in a mostly random structural state in aqueous solution but underwent high
      affinity association with dodecylphosphocholine micelles, where it adopted an
      ordered structure. The affinity of this peptide for the micellar surface and the
      structure of the bound peptide were independent of pH variation, surface charge,
      or attachment of a myristoyl anchor to the N-terminal. Studies with phospholipid
      vesicles suggested that the micellar structural results can be extrapolated to a
      true lipid bilayer. On the micellar surface all three sorting motifs are closely
      associated with the water/apolar interface: 72-YLRH and 87-LL lie within
      interfacial amphipathic helices, while 76-HPQY is non-helical and dimples just
      above the surface. These results contribute to the development of an
      understanding of the basis for specificity in recognition of sorting motifs by
      components of the cellular protein trafficking machinery.

PMID- 9651318
TI  - A leucine-based motif mediates the endocytosis of vesicular monoamine and
      acetylcholine transporters.
AB  - Specific transport proteins mediate the packaging of neurotransmitters into
      secretory vesicles and consequently require targeting to the appropriate
      intracellular compartment. To identify residues in the neuron-specific vesicular
      monoamine transporter (VMAT2) responsible for endocytosis, we examined the effect
      of amino (NH2-) and carboxyl (COOH-)-terminal mutations on steady state
      distribution and internalization. Deletion of a critical COOH-terminal domain
      sequence (AKEEKMAIL) results in accumulation of VMAT2 at the plasma membrane and
      a 50% reduction in endocytosis. Site-directed mutagenesis shows that replacement
      of the isoleucine-leucine pair within this sequence by alanine-alanine alone
      reduces endocytosis by 50% relative to wild type VMAT2. Furthermore, the KEEKMAIL
      sequence functions as an internalization signal when transferred to the plasma
      membrane protein Tac, and the mutation of the isoleucine-leucine pair also
      abolishes internalization of this protein. The closely related vesicular
      acetylcholine transporter (VAChT) contains a similar di-leucine sequence within
      the cytoplasmic COOH-terminal domain that when mutated results in accumulation of
      VAChT at the plasma membrane. The VAChT di-leucine sequence also confers
      internalization when appended to two other proteins and in one of these chimeras,
      conversion of the di-leucine sequence to di-alanine reduces the internalization
      rate by 50%. Both VMAT2 and VAChT thus use leucine-based signals for efficient
      endocytosis and as such are the first synaptic vesicle proteins known to use this
      motif for trafficking.

PMID- 9651319
TI  - Multiple epsilon-promoter elements participate in the developmental control of
      epsilon-globin genes in transgenic mice.
AB  - To delineate the regulation of the human epsilon-globin gene, we investigated
      epsilon-gene expression during the development of transgenic mice carrying
      constructs with epsilon-promoter truncations linked to a micro-locus control
      region (microLCR). Expression levels were compared with those of microLCR epsilon
      mice carrying a 2 kilobase epsilon-promoter and betaYAC controls. epsilon mRNA in
      the embryonic cells of microLCR (-179)epsilon mice were as high as in microLCR
      epsilon mice suggesting that the proximal epsilon-promoter contains most elements
      required for epsilon-gene activation. epsilon mRNA in adult microLCR (-179)
      epsilon mice was significantly lower than in the embryonic cells indicating that
      elements involved in epsilon-gene silencing are contained in the proximal epsilon
      promoter. Extension of the promoter sequence to -463 epsilon decreased epsilon
      gene expression in the definitive erythroid cells, supporting previous evidence
      that the -179 to -463epsilon region contains an epsilon-gene silencer. However,
      the epsilon-gene of the microLCR(-463)epsilon mice was not silenced in the
      definitive cells of fetal and adult erythropoiesis indicating that additional
      silencing elements are located upstream of position -463epsilon. These results
      provide in vivo evidence that multiple elements of the distal as well as the
      proximal promoter contribute to epsilon-gene silencing.

PMID- 9651320
TI  - Specificity of pyridinium inhibitors of the ubiquinone reduction sites in
      mitochondrial complex I.
AB  - Dual binding sites for pyridinium-type inhibitors in bovine heart mitochondrial
      complex I have been proposed (Gluck, M. R., Krueger, M. J., Ramsay, R. R.,
      Sablin, S. O., Singer, T. P., and Nicklas, W. J. (1994) J. Biol. Chem. 269, 3167
      3174). The marked biphasic nature of the dose-response curve for inhibition of
      the enzyme by MP-6(N-methyl-4-[2-(p-tert-butylbenzyl)propyl]pyridinium) makes
      this compound the first selective inhibitor of the two sites (Miyoshi, H., Inoue,
      M., Okamoto, S., Ohshima, M., Sakamoto, K., and Iwamura, H. (1997) J. Biol. Chem.
      272, 16176-16183). Modifications of the structure of MP-6 show that a tert-butyl
      group on the benzene ring, a methyl group attached to the pyridine nitrogen atom,
      para-substitution pattern in the pyridine ring, and the presence of a branched
      structure in the spacer moiety are important for the selective inhibition. On the
      basis of the structural specificity, we synthesized a selective inhibitor, MP-24
      (N-methyl-4-[2-methyl-2-(p-tert-butylbenzyl)propyl]pyridinium), which elicits
      greater selectivity. Characterization of the inhibitory behavior of MP-24
      provided further strong evidence for the dual binding sites model.

PMID- 9651321
TI  - Structure and transcriptional regulation of the human cystatin A gene. The 12-O
      tetradecanoylphorbol-13-acetate (TPA) responsive element-2 site (-272 to -278) on
      cystatin A gene is critical for TPA-dependent regulation.
AB  - Cystatin A, a cysteine proteinase inhibitor, is one of the precursor proteins of
      cornified cell envelope of keratinocytes and is expressed during the late stage
      of keratinocyte differentiation. We have isolated and characterized the human
      cystatin A gene. The cystatin A gene consists of three exons and two introns. The
      first, the second, and the third exons consist of coding sequences that are 66,
      102, and 126 base pairs in length, respectively. The first and the second introns
      consist of 14 and 3.6 kilobase pairs, respectively. The transcription initiation
      site was located 55 base pairs upstream from the first translation site. The
      fragment, +77 to -2595 in the 5'-flanking region of the human cystatin A gene,
      was subcloned into a chloramphenicol acetyltransferase (CAT) reporter vector. The
      expression vector, p2672CAT, produced a significant CAT activity in transiently
      transfected SV40-transformed human keratinocytes (SVHK cells), that were further
      stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA), a potent protein kinase
      C activator. Sequence analysis of the gene detected three TPA responsive elements
      (TRE-1, TRE-2, and TRE-3) and one AP-2 site on the 5' upstream promoter region.
      Deletion analyses of the p2672CAT vector demonstrated that TRE-2, which was
      located between -272 and -278, was critical for the regulation by TPA. Gel shift
      analyses revealed that c-Jun, JunD, and c-Fos bound to the TRE-2 region and that
      the p2672CAT activity level was elevated by co-transfection with c-Jun and c-Fos
      or with JunD and c-Fos expression vectors. Furthermore, co-transfection of SVHK
      cells with the protein kinase C-alpha expression vector and the p2672CAT
      expression vector also resulted in an increased CAT activity. These results
      indicate that the 5'-flanking region of the human cystatin A gene confers
      promoter activity and contains a TRE (TRE-2) that mediates, at least in part, the
      enhanced expression of this gene by TPA.

PMID- 9651322
TI  - Diversity of calcium signaling by metabotropic glutamate receptors.
AB  - During prolonged application of glutamate (20 min), patterns of increase in
      intracellular Ca2+ concentration ([Ca2+]i) were studied in HEK-293 cells
      expressing metabotropic glutamate receptor, mGluR1alpha or mGluR5a. Stimulation
      of mGluR1alpha induced an increase in [Ca2+]i that consisted of an initial
      transient peak with a subsequent steady plateau or an oscillatory increase in
      [Ca2+]i. The transient phase was largely attributed to Ca2+ mobilization from the
      intracellular Ca2+ stores, but the sustained phase was solely due to Ca2+ influx
      through the mGluR1alpha receptor-operated Ca2+ channel. Prolonged stimulation of
      mGluR5a continuously induced [Ca2+]i oscillations through mobilization of Ca2+
      from the intracellular Ca2+ stores. Studies on mutant receptors of mGluR1alpha
      and mGluR5a revealed that the coupling mechanism in the sustained phase of Ca2+
      response is determined by oscillatory/non-oscillatory patterns of the initial
      Ca2+ response but not by the receptor identity. In mGluR1alpha-expressing cells,
      activation of protein kinase C selectively desensitized the pathway for
      intracellular Ca2+ mobilization, but the mGluR1alpha-operated Ca2+ channel
      remained active. In mGluR5a-expressing cells, phosphorylation of mGluR5a by
      protein kinase C, which accounts for the mechanism of mGluR5a-controlled [Ca2+]i
      oscillations, might prevent desensitization and result in constant oscillatory
      mobilization of Ca2+ from intracellular Ca2+ stores. Our results provide a novel
      concept in which oscillatory/non-oscillatory mobilizations of Ca2+ induce
      different coupling mechanisms during prolonged stimulation of mGluRs.

PMID- 9651323
TI  - Herpes simplex virus inhibitor ICP47 destabilizes the transporter associated with
      antigen processing (TAP) heterodimer.
AB  - Chemical cross-linking of the transporter associated with antigen processing
      (TAP) heterodimer was used to determine whether the herpes simplex virus
      inhibitor of TAP, ICP47, induces a conformational change in TAP. Cross-linking of
      TAP in cellular membranes produced a major species of approximately 220 kDa which
      was comprised solely of TAP.1 and TAP.2 and most likely represents the TAP
      heterodimer. Interestingly, prior treatment of TAP-containing membranes with TAP
      peptide substrates stimulated the formation of the cross-linked TAP heterodimer,
      whereas pretreatment of membranes with ICP47 completely blocked the formation of
      the cross-linked heterodimer. These data suggest that suitable substrates for TAP
      stabilize the TAP heterodimer, whereas ICP47 destabilizes the heterodimer. The
      results indicate that subtle conformational changes occur in the TAP heterodimer
      upon the binding of peptides and the inhibitor ICP47 and that ICP47 has a
      deleterious effect on TAP heterodimer structure, in addition to its role as a
      potent blocker of substrate binding to TAP.

PMID- 9651324
TI  - Enhanced cholesterol efflux by tyrosyl radical-oxidized high density lipoprotein
      is mediated by apolipoprotein AI-AII heterodimers.
AB  - Myeloperoxidase secreted by phagocytes in the artery wall may be a catalyst for
      lipoprotein oxidation. High density lipoprotein (HDL) oxidized by peroxidase
      generated tyrosyl radical has a markedly enhanced ability to deplete cultured
      cells of cholesterol. We have investigated the structural modifications in
      tyrosylated HDL responsible for this effect. Spherical reconstituted HDL (rHDL)
      containing the whole apolipoprotein (apo) fraction of tyrosylated HDL reproduced
      the ability of intact tyrosylated HDL to enhance cholesterol efflux from
      cholesterol-loaded human fibroblasts when reconstituted with the whole lipid
      fraction of either HDL or tyrosylated HDL. Free apoAI or apoAII showed no
      increased capacity to induce cholesterol efflux from cholesterol-loaded
      fibroblasts following oxidation by tyrosyl radical, either in their lipid-free
      forms or in rHDL. The product of oxidation of a mixture of apoAI and apoAII (1:1
      molar ratio) by tyrosyl radical, however, reproduced the enhanced ability of
      tyrosylated HDL to induce cholesterol efflux when reconstituted with the whole
      lipid fraction of HDL. HDL containing only apoAI or apoAII showed no enhanced
      ability to promote cholesterol efflux following oxidation by tyrosyl radical,
      whereas HDL containing both apoAI and apoAII did. rHDL containing apoAI
      apoAIImonomer and apoAI-(apoAII)2 heterodimers showed a markedly increased
      ability to prevent the accumulation of LDL-derived cholesterol mass by sterol
      depleted fibroblasts compared with other apolipoprotein species of tyrosylated
      HDL. These results indicate a novel product of HDL oxidation, apoAI-apoAII
      heterodimers, with a markedly enhanced capacity to deplete cells of the
      regulatory pool of free cholesterol and total cholesterol mass. The recent
      observation of tyrosyl radical-oxidized LDL in vivo suggests that a similar
      modification of HDL would significantly enhance its ability to deplete peripheral
      cells of cholesterol in the first step of reverse cholesterol transport.

PMID- 9651325
TI  - Biosynthesis of branched polylactosaminoglycans. Embryonal carcinoma cells
      express midchain beta1,6-N-acetylglucosaminyltransferase activity that generates
      branches to preformed linear backbones.
AB  - Two types of beta1,6-GlcNAc transferases (IGnT6) are involved in in vitro
      branching of polylactosamines: dIGnT6 (distally acting), transferring to the
      penultimate galactose residue in acceptors like GlcNAcbeta1-3Galbeta1
      4GlcNAcbeta1-R, and cIGnT6 (centrally acting), transferring to the midchain
      galactoses in acceptors of the type (GlcNAcbeta1-3)Galbeta1-4GlcNAcbeta1
      3Galbeta1-+ ++4GlcNAcbeta1-R. The roles of the two transferases in the
      biosynthesis of branched polylactosamine backbones have not been clearly
      elucidated. We report here that cIGnT6 activity is expressed in human (PA1) and
      murine (PC13) embryonal carcinoma (EC) cells, both of which contain branched
      polylactosamines in large amounts. In the presence of exogenous UDP-GlcNAc,
      lysates from both EC cells catalyzed the formation of the branched
      pentasaccharide Galbeta1-4GlcNAcbeta1-3(GlcNAcbeta1-6)Galbeta1-4 GlcNAc from the
      linear tetrasaccharide Galbeta1-4GlcNAcbeta1-3Galbeta1-4GlcNAc. The PA1 cell
      lysates were shown to also catalyze the formation of the branched
      heptasaccharides Galbeta1-4GlcNAcbeta1-3Galbeta1-4GlcNAcbeta1-3(+ ++GlcNAcbeta1
      6)Galbeta1 -4GlcNAc and Galbeta1-4GlcNAcbeta1-3(GlcNAcbeta1-6)Galbeta1-+
      ++4GlcNAcbeta1-3Galbeta1 -4GlcNAc from the linear hexasaccharide Galbeta1
      4GlcNAcbeta1-3Galbeta1-4GlcNAcbeta1- 3Galbeta1-4GlcNAc in reactions
      characteristic to cIGnT6. By contrast, dIGnT6 activity was not detected in the
      lysates of the two EC cells that were incubated with UDP-GlcNAc and the acceptor
      trisaccharide GlcNAcbeta1-3Galbeta1-4GlcNAc. Hence, it appears likely that
      cIGnT6, rather than dIGnT6 is responsible for the synthesis of the branched
      polylactosamine chains in these cells.

PMID- 9651326
TI  - Truncation of amino acids 12-128 causes deregulation of the phosphatase activity
      of the sensor kinase KdpD of Escherichia coli.
AB  - The kdpFABC operon, which encodes the structural genes for the high affinity K+
      transport complex KdpFABC, is regulated by the sensor kinase KdpD and the
      response regulator KdpE. KdpD is a bifunctional enzyme catalyzing the
      autophosphorylation by ATP and the dephosphorylation of the corresponding
      response regulator KdpE. Here, we demonstrate that the phosphatase activity of
      KdpD is dependent on ATP, whereas GTP, ITP, CTP, ADP, and GDP have no effect. The
      phosphatase activity requires only ATP binding, because nonhydrolyzable analogs
      (adenosine-5'-[gamma-thio]triphosphate and adenosine-5'-[beta,gamma
      imido]triphosphate) work as well. However, KdpD proteins missing amino acids 12
      128 are characterized by a phosphatase activity that is independent of ATP. These
      proteins are still able to respond to K+ starvation, but an increase in
      osmolarity is no longer sensed. Comparison of different KdpD sequences reveals a
      conserved motif in this amino acid region that is very similar to a classical ATP
      binding site (Walker A motif). Replacement of the conserved Gly37, Lys38, and
      Thr39 residues in the consensus ATP-binding sequence results in a KdpD protein
      that causes a kdpFABC expression pattern comparable with that seen with KdpD
      proteins missing amino acids 12-128. However, in vitro phosphatase activity is
      comparable with that of wild-type KdpD. These results suggest that amino acids 12
      128 of KdpD are important for its activity and that an additional ATP-binding
      site in the N-terminal region seems to be involved in modulation of the
      phosphatase activity.

PMID- 9651327
TI  - Structure-function relationships in membrane segment 5 of the yeast Pma1 H+
      ATPase.
AB  - Membrane segment 5 (M5) is thought to play a direct role in cation transport by
      the sarcoplasmic reticulum Ca2+-ATPase and the Na+, K+-ATPase of animal cells. In
      this study, we have examined M5 of the yeast plasma membrane H+-ATPase by alanine
      scanning mutagenesis. Mutant enzymes were expressed behind an inducible heat
      shock promoter in yeast secretory vesicles as described previously (Nakamoto, R.
      K., Rao, R., and Slayman, C. W. (1991) J. Biol. Chem. 266, 7940-7949). Three
      substitutions (R695A, H701A, and L706A) led to misfolding of the H+-ATPase as
      evidenced by extreme sensitivity to trypsin; the altered proteins were arrested
      in biogenesis, and the mutations behaved genetically as dominant lethals. The
      remaining mutants reached the secretory vesicles in sufficient amounts to be
      characterized in detail. One of them (Y691A) had no detectable ATPase activity
      and appeared, based on trypsinolysis in the presence and absence of ligands, to
      be blocked in the E1-to-E2 step of the reaction cycle. Alanine substitution at an
      adjacent position (V692A) had substantial ATPase activity (54%), but was likewise
      affected in the E1-to-E2 step, as evidenced by shifts in its apparent affinity
      for ATP, H+, and orthovanadate. Among the mutants that were sufficiently active
      to be assayed for ATP-dependent H+ transport by acridine orange fluorescence
      quenching, none showed an appreciable defect in the coupling of transport to ATP
      hydrolysis. The only residue for which the data pointed to a possible role in
      cation liganding was Ser-699, where removal of the hydroxyl group (S699A and
      S699C) led to a modest acid shift in the pH dependence of the ATPase. This change
      was substantially smaller than the 13-30-fold decrease in K+ affinity seen in
      corresponding mutants of the Na+, K+-ATPase (Arguello, J. M., and Lingrel, J. B
      (1995) J. Biol. Chem. 270, 22764-22771). Taken together, the results do not give
      firm evidence for a transport site in M5 of the yeast H+-ATPase, but indicate a
      critical role for this membrane segment in protein folding and in the
      conformational changes that accompany the reaction cycle. It is therefore worth
      noting that the mutationally sensitive residues lie along one face of a putative
      alpha-helix.

PMID- 9651328
TI  - Biosynthesis of pteridines in Escherichia coli. Structural and mechanistic
      similarity of dihydroneopterin-triphosphate epimerase and dihydroneopterin
      aldolase.
AB  - An open reading frame located at 69.0 kilobases on the Escherichia coli
      chromosome was shown to code for dihydroneopterin aldolase, catalyzing the
      conversion of 7,8-dihydroneopterin to 6-hydroxymethyl-7,8-dihydropterin in the
      biosynthetic pathway of tetrahydrofolate. The gene was subsequently designated
      folB. The FolB protein shows 30% identity to the paralogous dihydroneopterin
      triphosphate epimerase, which is specified by the folX gene located at 2427
      kilobases on the E. coli chromosome. The folX and folB gene products were both
      expressed to high yield in recombinant E. coli strains, and the recombinant
      proteins were purified to homogeneity. Both enzymes form homo-octamers. Aldolase
      can use L-threo-dihydroneopterin and D-erythro-dihydroneopterin as substrates for
      the formation of 6-hydroxymethyldihydropterin, but it can also catalyze the
      epimerization of carbon 2' of dihydroneopterin and dihydromonapterin at
      appreciable velocity. Epimerase catalyzes the epimerization of carbon 2' in the
      triphosphates of dihydroneopterin and dihydromonapterin. However, the enzyme can
      also catalyze the cleavage of the position 6 side chain of several pteridine
      derivatives at a slow rate. Steady-state kinetic parameters are reported for the
      various enzyme-catalyzed reactions. We propose that the polarization of the 2'
      hydroxy group of the substrate could serve as the initial reaction step for the
      aldolase as well as for the epimerase activity. A deletion mutant obtained by
      targeting the folX gene of E. coli has normal growth properties on complete
      medium as well as on minimal medium. Thus, the physiological role of the E. coli
      epimerase remains unknown. The open reading frame ygiG of Hemophilus influenzae
      specifies a protein with the catalytic properties of an aldolase. However, the
      genome of H. influenzae does not specify a dihydroneopterin-triphosphate
      epimerase.

PMID- 9651329
TI  - Modulation of DNA binding of a tramtrack zinc finger peptide by the
      metallothionein-thionein conjugate pair.
AB  - The ability of metallothionein (MT) to modulate DNA binding by a two-finger
      peptide of Tramtrack (TTK), a CCHH zinc transcription factor, was investigated
      using metal-bound and metal-deficient forms of rabbit MT-2 and the TTK peptide.
      Thionein inhibited DNA binding by zinc-bound TTK, and Zn-MT restored DNA-binding
      by zinc-deficient apo-TTK. "Free" zinc at low concentrations was as effective as
      Zn-MT in restoring DNA binding by apopeptide but was inhibitory at concentrations
      equal to zinc bound to 2 mol eq and higher of Zn-MT. Substitution of cadmium for
      zinc reduced the affinity of the peptide for its DNA binding site. This effect
      was reversed by incubation with Zn-MT. The circular dichroic spectra of the TTK
      peptide indicated that zinc removal resulted in loss of alpha-helical structures,
      which are sites of DNA contact points. Reconstitution with cadmium resulted in
      stoichiometric substitution of 2 mol of Cd/mol of peptide but not recovery of
      alpha-helical structures. Incubation of Cd-TTK with Zn-MT restored the secondary
      structure expected for zinc-bound TTK. The ability of Zn-MT and thionein to
      restore or inhibit DNA-binding by TTK was associated with effects on the
      metallation status of the peptide and related alterations in its secondary
      structure.

PMID- 9651330
TI  - Matrilin-3 forms disulfide-linked oligomers with matrilin-1 in bovine epiphyseal
      cartilage.
AB  - A comparison of noncollagenous matrix proteins from different types of bovine
      cartilage by SDS-polyacrylamide gel electrophoresis showed a prominent 240-kDa
      component in extracts of epiphyseal but not tracheal tissue. On amino-terminal
      sequence analysis, it gave two sequences. One matched the NH2 terminus of
      cartilage matrix protein (CMP) as reported for tracheal cartilage. The other did
      not match any known protein sequence. Further analysis of the 240-kDa protein
      after reduction of disulfides resolved two bands on SDS-polyacrylamide gel
      electrophoresis. Isolation and sequence analysis of tryptic peptides confirmed
      that one was bovine CMP and the other a CMP homolog. A data base search
      identified the latter as matrilin-3, a molecule recently predicted from human and
      mouse cDNA sequences (Wagener, R., Kobbe, B., and Paulsson, M. (1997) FEBS Lett.
      413, 129-134). Matrilin-3 and CMP (matrilin-1) were prominent in equimolar
      amounts in fetal bovine epiphyseal cartilage and absent from adult articular
      cartilage. Adult tracheal cartilage contained almost exclusively CMP. Although
      the mechanism of polymeric assembly is unknown, the matrilin-3 chain appears to
      function in the matrix linked to matrilin-1 in the form of disulfide-bonded
      heteromeric molecules. The results indicate a molecular stoichiometry of
      (matrilin-1)2(matrilin-3)2.

PMID- 9651331
TI  - UV-B-induced differential transcription of psbA genes encoding the D1 protein of
      photosystem II in the Cyanobacterium synechocystis 6803.
AB  - UV-B irradiation of intact Synechocystis sp. PCC 6803 cells results in the loss
      of photosystem II activity, which can be repaired via de novo synthesis of the D1
      (and D2) reaction center subunits. In this study, we investigated the effect of
      UV-B irradiation on the transcription of the psbA2 and psbA3 genes encoding
      identical D1 proteins. We show that UV-B irradiation increases the level of psbA2
      mRNA 2-3-fold and, more dramatically, it induces a 20-30-fold increase in the
      accumulation of the psbA3 mRNA even at levels of irradiation too low to produce
      losses of either photosystem II activity or D1 protein. The induction of psbA3
      transcript accumulation is specific for UV-B light (290-330 nm). Low intensity UV
      A emission (330-390 nm) and white light induce only a small, at most, 2-3-fold
      enhancement, whereas no effect of blue light was observed. Expression patterns of
      chimeric genes containing the promoter regions of the psbA2, psbA3 genes fused to
      the firefly luciferase (luc) reporter gene indicate that (i) transcription of
      psbA2/luc and psbA3/luc transgenes was elevated, similarly to that of the
      endogenous psbA genes, by UV-B irradiation, and that (ii) a short, 80-base pair
      psbA3 promoter fragment is sufficient to maintain UV-B-induced transcription of
      the luc reporter gene. Furthermore, our findings indicate that UV-B-induced
      expression of the psbA2 and psbA3 genes is a defense response against UV-B
      stress, which is regulated, at least, partially at the level of transcription and
      does not require active electron transport.

PMID- 9651332
TI  - Hydrolysis of phosphodiesters through transformation of the bacterial
      phosphotriesterase.
AB  - The phosphotriesterase from Pseudomonas diminuta catalyzes the hydrolysis of a
      wide array of phosphotriesters and related phosphonates, including
      organophosphate pesticides and military nerve agents. It has now been shown that
      this enzyme can also catalyze the hydrolysis of phosphodiesters, albeit at a
      greatly reduced rate. However, the enzymatic hydrolysis of ethyl-4-nitrophenyl
      phosphate (compound I) by the wild-type enzyme was >10(8) times faster than the
      uncatalyzed reaction (kcat = 0.06 s-1 and Km = 38 mM). Upon the addition of
      various alkylamines to the reaction mixture, the kcat/Km for the phosphodiester
      (compound I) increased up to 200-fold. Four mutant enzymes of the
      phosphotriesterase were constructed in a preliminary attempt to improve
      phosphodiester hydrolysis activity of the native enzyme. Met-317, which is
      thought to reside in close proximity to the pro-S-ethoxy arm of the paraoxon
      substrate, was mutated to arginine, alanine, histidine, and lysine. These mutant
      enzymes showed slight improvements in the catalytic hydrolysis of organophosphate
      diesters. The M317K mutant enzyme displayed the most improvement in catalytic
      activity (kcat = 0.34 s-1 and Km = 30 mM). The M317A mutant enzyme catalyzed the
      hydrolysis of the phosphodiester (compound I) in the presence of alkylamines up
      to 200 times faster than the wild-type enzyme in the absence of added amines. The
      neutralization of the negative charge on the oxygen atom of the phosphodiester by
      the ammonium cation within the active site is thought to be responsible for the
      rate enhancement by these amines in the hydrolytic reaction. These results
      demonstrate that an active site optimized for the hydrolysis of organophosphate
      triesters can be made to catalyze the hydrolysis of organophosphate diesters.

PMID- 9651333
TI  - Characterization of aggrecan retained and lost from the extracellular matrix of
      articular cartilage. Involvement of carboxyl-terminal processing in the
      catabolism of aggrecan.
AB  - The catabolism of aggrecan in bovine articular cartilage explants is
      characterized by the release into the culture medium of high molecular weight
      aggrecan fragments, generated by the proteolytic cleavage of the core protein
      between residues Glu373 and Ala374 within the interglobular domain. In this
      study, the position of the carboxyl-terminus of these aggrecan fragments, as well
      as a major proteolytically shortened aggrecan core protein present in cartilage
      matrix, have been deduced by characterizing the peptides generated by the
      reaction of aggrecan core protein peptides with cyanogen bromide. It was shown
      that two out of three such peptide fragments having an amino terminus starting at
      Ala374 have their carboxyl terminus located within the chondroitin sulfate 1
      domain. The third and largest aggrecan core protein peptide, with an amino
      terminus starting at Ala374, has a carboxyl terminus in a region of core protein
      between the chondroitin sulfate 1 domain and the chondroitin sulfate 2 domain.
      The carboxyl terminus of this peptide appeared to be the same as that of the
      proteolytically degraded aggrecan core protein, which is retained within the
      extracellular matrix of the tissue. Another two aggrecan fragments recovered from
      the medium of explant cultures with amino-terminal sequences in the chondroitin
      sulfate 2 domain at Ala1772 and Leu1872 were shown to have their carboxyl termini
      within the G3 globular domain. These results suggest that the catabolism of
      aggrecan between residues Glu373 and Ala374 in the interglobular domain by the
      putative proteinase, aggrecanase, may be dependent on prior proteolytic
      processing within the carboxyl-terminal region of the core protein.

PMID- 9651334
TI  - Antichymotrypsin interaction with chymotrypsin. Reactions following encounter
      complex formation.
AB  - Serpins, serine proteinase inhibitors, form enzymatically inactive, 1:1 complexes
      (denoted E*I*) with their target proteinases, that only slowly release I*, in
      which the P1-P1' linkage is cleaved. Recently we presented evidence that the
      serpin antichymotrypsin (ACT, I) reacts with the serine proteinase chymotrypsin
      (Chtr, E) to form an E*I* complex via a three-step mechanism, E + I <==> E .I
      <==> EI' <==> E*I* in which EI', which retains the P1-P1' linkage, is formed in a
      partly or largely rate-determining step, depending on temperature (O'Malley, K.
      H, Nair, S. A., Rubin, H., and Cooperman, B. S. (1997) J. Biol. Chem. 272, 5354
      5359). Here we extend these studies through the introduction of a new assay for
      the formation of the postcomplex fragment, corresponding to ACT residues 359 (the
      P1' residue) to 398 (the C terminus), coupled with rapid quench flow kinetic
      analysis. We show that the E.I encounter complex of wild type-rACT and Chtr forms
      both E*I* and postcomplex fragment with the same rate constant, so that both
      species arise from EI' conversion to E*I*. These results support our earlier
      conclusion that the P1-P1' linkage is preserved in EI' and imply that E*I*
      corresponds to a covalent adduct of E and I, either acyl enzyme or the
      tetrahedral intermediate formed by water attack on acyl enzyme. Furthermore, we
      show that the A347R (P12) variant of rACT, which is a substrate rather than an
      inhibitor of Chtr, has a rate constant for postcomplex fragment formation from
      the E.I complex very similar to that observed for WT-rACT, implying that EI' is
      the common intermediate from which partitioning to inhibitor and substrate
      pathways occurs. These results are used to elaborate a proposed scheme for ACT
      interaction with Chtr that is considered in the light of relevant results from
      studies of other serpin-serine proteinase pairs.

PMID- 9651335
TI  - Zinc cluster proteins Leu3p and Uga3p recognize highly related but distinct DNA
      targets.
AB  - Members of the family of fungal zinc cluster DNA-binding proteins possess 6
      highly conserved cysteines that bind to two zinc atoms forming a structure
      (Zn2Cys6) that is required for recognition of specific DNA sequences. Many zinc
      cluster proteins have been shown to bind as homodimers to a pair of CGG triplets
      oriented either as direct (CGG NX CGG), inverted (CGG NX CCG), or everted repeats
      (CCG NX CGG), where N indicates nucleotides. Variation in the spacing between the
      CGG triplets also contributes to the diversity of sites recognized. For example,
      Leu3p binds to the everted sequence CCG N4 CGG with a strict requirement for a 4
      base pair spacing. Here, we show that another member of the family, Uga3p,
      recognizes the same DNA motif as Leu3p. However, these transcription factors have
      distinct DNA targets. We demonstrate that additional specificity of binding is
      provided by nucleotides located between the two everted CGG triplets. Altering
      the 4 nucleotides between to the two everted CGG triplets switches the
      specificity from a Uga3p site to a Leu3p site in both in vitro and in vivo
      assays. Thus, our results identify a new mechanism that expands the repertoire of
      DNA targets of the family of zinc cluster proteins. These experiments provide a
      model for discrimination between targets of zinc cluster proteins.

PMID- 9651336
TI  - Stimulation of type 1 and type 8 Ca2+/calmodulin-sensitive adenylyl cyclases by
      the Gs-coupled 5-hydroxytryptamine subtype 5-HT7A receptor.
AB  - The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) plays an important
      regulatory role in developing and adult nervous systems. With the exception of
      the 5-HT3 receptor, all of the cloned serotonin receptors belong to the G protein
      coupled receptor superfamily. Subtypes 5-HT6 and 5-HT7 couple to stimulation of
      adenylyl cyclases through Gs and display high affinities for antipsychotic and
      antidepressant drugs. In the brain, mRNA for 5-HT6 is found at high levels in the
      hippocampus, striatum, and nucleus accumbens. 5-HT7 mRNA is most abundant in the
      hippocampus, neocortex, and hypothalamus. To better understand how serotonin
      might control cAMP levels in the brain, we coexpressed 5-HT6 or 5-HT7A receptors
      with specific isoforms of adenylyl cyclase in HEK 293 cells. The 5-HT6 receptor
      functioned as a typical Gs-coupled receptor in that it stimulated AC5, a Gs
      sensitive adenylyl cyclase, but not AC1 or AC8, calmodulin (CaM)-stimulated
      adenylyl cyclases that are not activated by Gs-coupled receptors in vivo.
      Surprisingly, serotonin activation of 5-HT7A stimulated AC1 and AC8 by increasing
      intracellular Ca2+. 5-HT also increased intracellular Ca2+ in primary neuron
      cultures. These data define a novel mechanism for the regulation of intracellular
      cAMP by serotonin.

PMID- 9651337
TI  - Reactive oxygen species- and dimerization-induced activation of apoptosis signal
      regulating kinase 1 in tumor necrosis factor-alpha signal transduction.
AB  - Reactive oxygen species (ROS) have been implicated in the induction of apoptosis
      by tumor necrosis factor-alpha (TNFalpha) and other cytotoxic insults, although
      the molecule(s) regulated by ROS in TNFalpha signaling have not been identified.
      Apoptosis signal-regulating kinase 1 (ASK1) is a member of the mitogen-activated
      protein kinase kinase kinase (MAPKKK) superfamily that has been shown to be
      activated during TNFalpha-induced apoptosis. ASK1 increases apoptosis when
      overexpressed, but the mechanism of ASK1 activation and the mechanisms of ASK1
      induced apoptosis are unclear. We now report that hydrogen peroxide induces the
      activation of ASK1 in 293 cells. TNFalpha-induced activation of ASK1 was
      inhibited by antioxidants. Hydrogen peroxide-induced apoptosis was markedly
      enhanced by the expression of ASK1. These results suggest that TNFalpha-induced
      activation of ASK1 is mediated by ROS. We also examined how ASK1 activity is
      regulated by ROS. We found that ASK1 formed dimers or higher order oligomers in
      293 cells. TNFalpha or hydrogen peroxide treatment increased the dimeric form of
      ASK1, and pretreatment with N-acetylcysteine decreased it. Furthermore, synthetic
      dimerization of an ASK1-gyrase B fusion protein by coumermycin resulted in
      substantial activation of ASK1, suggesting that dimerization of ASK1 is
      sufficient for its activation. These results taken together suggest that TNFalpha
      causes ASK1 activation via ROS-mediated dimerization of ASK1.

PMID- 9651338
TI  - Apolipoprotein E2 reduces the low density lipoprotein level in transgenic mice by
      impairing lipoprotein lipase-mediated lipolysis of triglyceride-rich
      lipoproteins.
AB  - Apolipoprotein (apo) E2 is often associated with low levels of low density
      lipoprotein (LDL) cholesterol and high levels of plasma triglycerides in humans.
      Mice expressing apoE2 also have low LDL levels. To evaluate the possible role of
      the LDL receptor in the cholesterol-lowering effect of apoE2, we bred transgenic
      mice expressing low levels of apoE2 with LDL receptor-null mice (hE2(+/0), LDLR-/
      ). Even in the absence of the LDL receptor, plasma total and LDL cholesterol
      levels decreased progressively with increasing levels of plasma apoE2. At plasma
      apoE2 levels >20 mg/dl, LDL cholesterol was approximately 45% lower than in LDLR
      /- mice. Thus, the LDL cholesterol-lowering effect of apoE2 is independent of the
      LDL receptor. In contrast, plasma triglyceride levels increased (mostly in very
      low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL))
      progressively as apoE2 levels increased. At plasma apoE2 levels >20 mg/dl,
      triglycerides were approximately 150% higher than in LDLR-/- mice. Furthermore,
      in apoE-null mice (hE2(+/0), mE-/-), apoE2 levels also correlated positively with
      plasma triglyceride levels, suggesting impaired lipolysis in both hE2(+/0),LDLR-/
      and hE2(+/0),mE-/- mice. Incubating VLDL or IDL from the hE2(+/0),LDLR-/- or the
      hE2(+/0),mE-/- mice with mouse postheparin plasma inhibited lipoprotein lipase
      mediated lipolysis of apoE2-containing VLDL and IDL by approximately 80 and
      approximately 70%, respectively, versus normal VLDL and IDL. This observation was
      confirmed by studies with triglyceride-rich emulsion particles, apoE2, and
      purified lipoprotein lipase. Furthermore, apoE2-containing VLDL had much less
      apoC-II than normal VLDL. Adding apoC-II to the incubation partially corrected
      the apoE2-impaired lipolysis in apoE2-containing VLDL or IDL and corrected it
      completely in apoE2-containing emulsion particles. Thus, apoE2 lowers LDL
      cholesterol by impairing lipoprotein lipase-mediated lipolysis of triglyceride
      rich lipoproteins (mostly by displacing or masking apoC-II). Furthermore, the
      effects of apoE2 on both plasma cholesterol and triglyceride levels are dose
      dependent and act via different mechanisms. The increase in plasma cholesterol
      caused by apoE2 is due mostly to impaired clearance, whereas the increase in
      plasma triglycerides is caused mainly by apoE2-impaired lipolysis of triglyceride
      rich lipoproteins.

PMID- 9651339
TI  - Evidence that IRS-2 phosphorylation is required for insulin action in
      hepatocytes.
AB  - Insulin receptor substrates (IRSs) are tyrosine-phosphorylated following
      stimulation with insulin, insulin-like growth factors (IGFs), and interleukins. A
      key question is whether different IRSs play different roles to mediate insulin's
      metabolic and growth-promoting effects. In a novel system of insulin receptor
      deficient hepatocytes, insulin fails to (i) stimulate glucose phosphorylation,
      (ii) enhance glycogen synthesis, (iii) suppress glucose production, and (iv)
      promote mitogenesis. However, insulin's ability to induce IRS-1 and gab-1
      phosphorylation and binding to phosphatidylinositol (PI) 3-kinase is unaffected,
      by virtue of the compensatory actions of IGF-1 receptors. In contrast,
      phosphorylation of IRS-2 and generation of IRS-2/PI 3-kinase complexes are
      markedly reduced. Thus, absence of insulin receptors selectively reduces IRS-2,
      but not IRS-1 phosphorylation, and the impairment of IRS-2 activation is
      associated with lack of insulin effects. To address whether phosphorylation of
      additional IRSs is also affected, we analyzed phosphotyrosine-containing proteins
      in PI 3-kinase immunoprecipitates from insulin-treated cells. However, these
      experiments indicate that IRS-1 and IRS-2 are the main PI 3-kinase-bound proteins
      in hepatocytes. These data identify IRS-2 as the main effector of both the
      metabolic and growth-promoting actions of insulin through PI 3-kinase in
      hepatocytes, and IRS-1 as the main substrate mediating the mitogenic actions of
      IGF-1 receptors.

PMID- 9651340
TI  - Cross-talk between 5-hydroxytryptamine receptors in a serotonergic cell line.
      Involvement of arachidonic acid metabolism.
AB  - The study of signaling cascades and of functional interactions between 5
      hydroxytryptamine (5-HT) receptor pathways with heterogenous brain cell
      populations remains an arduous task. We took advantage of a serotonergic cell
      line to elucidate cross-talks between 5-HT receptors and to demonstrate the
      involvement of two 5-HT2 receptor subtypes in the regulation of 5-HT1B/1D
      function. The inducible 1C11 cell line has the unique property of acquiring
      within 4 days a complete serotonergic phenotype (1C11* cells), including three 5
      HT receptors. 5-HT1B/1D and 5-HT2B receptors are expressed since day 2 of the
      serotonergic differentiation while 5-HT2A receptors are induced at day 4. We
      first established that 5-HT2B receptors are coupled with the phospholipase A2
      (PLA2)-mediated release of arachidonic acid (AA) and that the activation of 5
      HT2B receptors in 1C11*d2 cells inhibits the 5-HT1B/1D receptor function via a
      cyclooxygenase-dependent AA metabolite. At day 4, this 5-HT2B-mediated inhibition
      of the 5-HT1B/1D function can be blocked upon concomitant 5-HT2A activation
      although a 5-HT2A/PLA2 positive coupling was evidenced. This suggests the
      existence in 1C11*d4 cells of pathway(s) for 5-HT2A receptors, distinct from PLC
      and PLA2. Finally, this study reveals the antagonistic roles of 5-HT2A and 5-HT2B
      receptors in regulating the function of 5-HT1B/1D, a receptor involved in
      neuropsychiatric disorders and migraine pathogenesis.

PMID- 9651341
TI  - Endocytosis of the glucose transporter GLUT4 is mediated by the GTPase dynamin.
AB  - To study the role of the GTPase dynamin in GLUT4 intracellular recycling, we have
      overexpressed dynamin-1 wild type and a GTPase-negative mutant (K44A) in primary
      rat adipose cells. Transfection was accomplished by electroporation using an
      hemagglutinin (HA)-tagged GLUT4 as a reporter protein. In cells expressing HA
      GLUT4 alone, insulin results in an approximately 7-fold increase in cell surface
      anti-HA antibody binding. Studies with wortmannin indicate that the kinetics of
      HA-GLUT4-trafficking parallel those of the native GLUT4 and in addition, that
      newly synthesized HA-GLUT4 goes to the plasma membrane before being sorted into
      the insulin-responsive compartments. Short term (4 h) coexpression of dynamin
      K44A and HA-GLUT4 increases the amount of cell surface HA-GLUT4 in both the basal
      and insulin-stimulated states. Under conditions of maximal expression of dynamin
      K44A (24 h), most or all of the intracellular HA-GLUT4 appears to be present on
      the cell surface in the basal state, and insulin has no further effect.
      Measurements of the kinetics of HA-GLUT4 endocytosis show that dynamin-K44A
      blocks internalization of the glucose transporters. In contrast, expression of
      dynamin wild type decreases the amount of cell surface HA-GLUT4 in both the basal
      and insulin-stimulated states. These data demonstrate that the endocytosis of
      GLUT4 is largely mediated by processes which require dynamin.

PMID- 9651342
TI  - Directed mutations in the poorly defined region of porcine liver fructose-1,6
      bisphosphatase significantly affect catalysis and the mechanism of AMP
      inhibition.
AB  - Asn64, Asp68, Lys71, Lys72, and Asp74 of porcine liver fructose-1, 6
      bisphosphatase (FBPase) are conserved residues and part of a loop for which no
      electron density has been observed in crystal structures. Yet mutations of the
      above dramatically affect catalytic rates and/or AMP inhibition. The Asp74 -->
      Ala and Asp74 --> Asn mutant enzymes exhibited 50,000- and 2,000-fold reductions,
      respectively, in kcat relative to wild-type FBPase. The pH optimum for the
      catalytic activity of the Asp74 --> Glu, Asp68 --> Glu, Asn64 --> Gln, and Asn64 
      -> Ala mutant enzymes shifted from pH 7.0 (wild-type enzyme) to pH 8.5, whereas
      the Lys71 --> Ala mutant and Lys71,72 --> Met double mutant had optimum activity
      at pH 7.5. Mg2+ cooperativity, Km for fructose 1,6-bisphosphate, and Ki for
      fructose 2,6-bisphosphate were comparable for the mutant and wild-type enzymes.
      Nevertheless, for the Asp74 --> Glu, Asp68 --> Glu, Asn64 --> Gln, and Asn64 -->
      Ala mutants, the binding affinity for Mg2+ decreased by 40-125-fold relative to
      the wild-type enzyme. In addition, the Asp74 --> Glu and Asn64 --> Ala mutants
      exhibited no AMP cooperativity, and the kinetic mechanism of AMP inhibition with
      respect to Mg2+ was changed from competitive to noncompetitive. The double
      mutation Lys71,72 --> Met increased Ki for AMP by 175-fold and increased Mg2+
      affinity by 2-fold relative to wild-type FBPase. The results reported here
      strongly suggest that loop 51-72 is important for catalytic activity and the
      mechanism of allosteric inhibition of FBPase by AMP.

PMID- 9651343
TI  - Nucleosome unfolding during DNA repair in normal and xeroderma pigmentosum (group
      C) human cells.
AB  - The fate of nucleosomes during nucleotide excision repair is unclear. We have
      used organomercurial chromatography to capture accessible thiol groups of
      proteins at (or near) nascent repair sites in normal and xeroderma pigmentosum
      (group C) human cells. The reactive groups include cysteine 110 of histone H3,
      which is exposed in unfolded nucleosomes. Immediately after UV irradiation and a
      short pulse labeling of repair patches, intact nuclei were digested with
      restriction enzymes to release approximately 18% of the chromatin into soluble
      fragments, which are enriched (approximately 4-fold) in a constitutively
      transcribed gene. Upon organomercurial affinity fractionation, approximately 1.8%
      of the soluble chromatin remains bound in high salt (0.5 M NaCl) and is released
      with dithiothreitol. In normal cell chromatin, this fraction is enriched in
      nascent repair patches (1.5-1.8-fold) over the unbound fraction. This enrichment
      decreases following short chase periods with a time course similar to the loss of
      enhanced nuclease sensitivity of these regions (t 1/2 approximately 30 min). Much
      less enrichment of nascent repair patches is observed in the thiol-reactive
      fraction from XPC cells, which repair primarily the transcribed strand of active
      genes. These results suggest that transient nucleosome unfolding occurs during
      nucleotide excision repair in normal human cells, and this unfolding may require
      the XPC protein.

PMID- 9651344
TI  - The ets family member Tel binds to the Fli-1 oncoprotein and inhibits its
      transcriptional activity.
AB  - The tel gene, recently shown to be translocated in a spectrum of acute and
      chronic human leukemias, belongs to the ets family of sequence-specific
      transcription factors. To determine the role of Tel in normal hematopoietic
      development, we used the tel gene as the bait in the yeast two-hybrid system to
      screen a hematopoietic stem cell library. Two partners were identified: Tel binds
      to itself, and Tel binds to the ets family member Fli-1. In vitro and in vivo
      assays confirmed these interactions. In transient transfection assays, Fli-1
      transactivates megakaryocytic specific promoters, and Tel inhibits this effect of
      Fli-1. Transactivation studies using deletion mutants of Tel, and the Tel-AML-1
      fusion protein, indicate that the helix-loop-helix domain of Tel only partially
      inhibits transactivation and that complete inhibition requires the full-length
      Tel molecule, including the DNA binding domain. The Tel and Fli-1 proteins are
      expressed early in hematopoiesis, and the inability of Tel fusion proteins such
      as Tel-AML-1 to counteract Fli-1 mediated transactivation may contribute to the
      malignant phenotype in human leukemias where this fusion protein is present.

PMID- 9651345
TI  - Human beta-filamin is a new protein that interacts with the cytoplasmic tail of
      glycoprotein Ibalpha.
AB  - We have cloned and sequenced a 9.4-kilobase cDNA specifying a new 280-kDa protein
      interacting with the cytoplasmic tail of glycoprotein (Gp) Ibalpha and showing
      considerable homology to actin-binding protein 280 (ABP-280) and chicken retinal
      filamin. We term this protein human beta-filamin. The gene for beta-filamin
      localizes to chromosome 3p14.3-p21.1. beta-Filamin mRNA expression was observed
      in many tissues and in cultured human umbilical vein endothelial cells (HUVECs);
      only minimal expression was detected in platelets and the megakaryocytic cell
      line CHRF-288. Like ABP-280, beta-filamin contains an NH2-terminal actin-binding
      domain, a backbone of 24 tandem repeats, and two "hinge" regions. A polyclonal
      antibody to the unique beta-filamin first hinge sequence identifies a strong 280
      kDa band in HUVECs but only a weak band in platelets, and stains normal human
      endothelial cells in culture and in situ. We have confirmed the interaction of
      beta-filamin and GpIbalpha in platelet and HUVEC lysates. In addition, using two
      hybrid analysis with deletion mutants, we have localized the binding domain for
      GpIbalpha in beta-filamin to residues 1862-2148, an area homologous to the
      GpIbalpha binding domain in ABP-280. beta-Filamin is a new member of the filamin
      family that may have significance for GpIbalpha function in endothelial cells and
      platelets.

PMID- 9651346
TI  - Polynucleotide phosphorylase is a component of a novel plant poly(A) polymerase.
AB  - We have isolated cDNA clones encoding a novel RNA-binding protein that is a
      component of a multisubunit poly(A) polymerase from pea seedlings. The encoded
      protein bears a significant resemblance to polynucleotide phosphorylases
      (PNPases) from bacteria and chloroplasts. More significantly, this RNA-binding
      protein is able to degrade RNAs with the resultant production of nucleotide
      diphosphates, and it can add extended polyadenylate tracts to RNAs using ADP as a
      donor for adenylate moieties. These activities are characteristic of PNPase.
      Antibodies raised against the cloned protein simultaneously immunoprecipitate
      both poly(A) polymerase and PNPase activity. We conclude from these studies that
      PNPase is the RNA-binding cofactor for this poly(A) polymerase and is an integral
      player in the reaction catalyzed by this enzyme. The identification of this RNA
      binding protein as PNPase, which is a chloroplast-localized enzyme known to be
      involved in mRNA 3'-end determination and turnover (Hayes, R., Kudla, J.,
      Schuster, G., Gabay, L., Maliga, P., and Gruissem, W. (1996) EMBO J. 15, 1132
      1141), raises interesting questions regarding the subcellular location of the
      poly(A) polymerase under study. We have reexamined this issue, and we find that
      this enzyme can be detected in chloroplast extracts. The involvement of PNPase in
      polyadenylation in vitro provides a biochemical rationale for the link between
      chloroplast RNA polyadenylation and RNA turnover which has been noted by others
      (Lisitsky, I., Klaff, P., and Schuster, G. (1996) Proc. Natl. Acad. Sci. U. S. A.
      93, 13398-13403).

PMID- 9651348
TI  - Iron uptake by the halotolerant alga Dunaliella is mediated by a plasma membrane
      transferrin.
AB  - A 150-kDa transferrin-like protein (Ttf) is associated with the plasma membrane
      of the halotolerant unicellular alga Dunaliella salina (Fisher, M., Gokhman, I.,
      Pick, U., and Zamir, A. (1997) J. Biol. Chem. 272, 1565-1570). The Ttf level
      rises with medium salinity or upon iron depletion. Evidence that Ttf is involved
      in iron uptake by Dunaliella is presented here. Algal iron uptake exhibits
      characteristics resembling those of animal transferrins: high specificity and
      affinity for Fe3+ ions, strict dependence on carbonate/bicarbonate ions, and very
      low activity in acidic pH. Reducing the level of Ttf by mild proteolysis of whole
      cells is accompanied by lowered uptake activity. Conversely, accumulation of high
      levels of Ttf is correlated with an enhancement of iron uptake. Kinetically, iron
      uptake consists of two steps: an energy-independent binding of iron to the cell
      surface and an energy-dependent internalization. Salinities as high as 3.5 M NaCl
      do not inhibit iron uptake or decrease the apparent affinity for Fe3+ ions,
      implying that Ttf activity is not affected by high salt. These results indicate
      that transferrins, hitherto identified only in animals, are present and function
      in iron transport also in plant systems.

PMID- 9651347
TI  - Mutagenesis of the C2 domain of protein kinase C-alpha. Differential roles of
      Ca2+ ligands and membrane binding residues.
AB  - The C2 domains of conventional protein kinase C (PKC) have been implicated in
      their Ca2+-dependent membrane binding. The C2 domain of PKC-alpha contains
      several Ca2+ ligands that bind multiple Ca2+ ions and other putative membrane
      binding residues. To understand the roles of individual Ca2+ ligands and protein
      bound Ca2+ ions in the membrane binding and activation of PKC-alpha, we mutated
      five putative Ca2+ ligands (D187N, D193N, D246N, D248N, and D254N) and measured
      the effects of mutations on vesicle binding, enzyme activity, and monolayer
      penetration of PKC-alpha. Altered properties of these mutants indicate that
      individual Ca2+ ions and their ligands have different roles in the membrane
      binding and activation of PKC-alpha. The binding of Ca2+ to Asp187, Asp193, and
      Asp246 of PKC-alpha is important for the initial binding of protein to membrane
      surfaces. On the other hand, the binding of another Ca2+ to Asp187, Asp246,
      Asp248, and Asp254 induces the conformational change of PKC-alpha, which in turn
      triggers its membrane penetration and activation. Among these Ca2+ ligands,
      Asp246 was shown to be most essential for both membrane binding and activation of
      PKC-alpha, presumably due to its coordination to multiple Ca2+ ions. Furthermore,
      to identify the residues in the C2 domain that are involved in membrane binding
      of PKC-alpha, we mutated four putative membrane binding residues (Trp245, Trp247,
      Arg249, and Arg252). Membrane binding and enzymatic properties of two double-site
      mutants (W245A/W247A and R249A/R252A) indicate that Arg249 and Arg252 are
      involved in electrostatic interactions of PKC-alpha with anionic membranes,
      whereas Trp245 and Trp247 participate in its penetration into membranes and
      resulting hydrophobic interactions. Taken together, these studies provide the
      first experimental evidence for the role of C2 domain of conventional PKC as a
      membrane docking unit as well as a module that triggers conformational changes to
      activate the protein.

PMID- 9651349
TI  - Induction of a caspase-3-like activity by calcium in normal cytosolic extracts
      triggers nuclear apoptosis in a cell-free system.
AB  - Calcium is involved in several steps of the apoptotic process. In nuclei,
      endonucleases are presumed to be the main targets of calcium; however, little is
      known about its role during the cytosolic phase of apoptosis. We used a cell-free
      system to address this question. Our results show that CaCl2 triggered nuclear
      apoptosis (i.e. typical morphological change and DNA fragmentation) at
      concentrations of 5 mM. This concentration was lowered 10-fold by the co
      incubation with cytosolic extracts from nonapoptotic cells. Apoptotic changes
      induced by the incubation of nuclei with CaCl2 in the presence of these cytosols
      were strongly reduced in the presence of an inhibitor of caspase-3 and to a
      lesser extent by an inhibitor of caspase-1. We also show that calcium-induced
      apoptosis is affected by protease inhibitors such as N-tosyl-L-phenylalanine
      chloromethyl ketone, but not by calpain or several lysosomal protease inhibitors.
      The addition of CaCl2 to the cell-free system increased a caspase-3 activity in
      nonapoptotic cytosols as shown by specific antibodies and an enzymatic assay. No
      activation of a caspase-3-like activity by the addition of cytochrome c was
      observed in these extracts under similar conditions. The enhanced caspase-3
      activity induced by calcium was inhibited by protease inhibitors affecting
      morphological nuclear apoptosis except for those responsible for the degradation
      of lamin A. These results suggest that CaCl2 could trigger, in normal cells, an
      apoptotic cascade through the activation of cytosolic caspase-3 activity.

PMID- 9651350
TI  - Identification of a novel cadherin (vascular endothelial cadherin-2) located at
      intercellular junctions in endothelial cells.
AB  - Endothelial cells express two major cadherins, VE- and N-cadherins, but only the
      former consistently participates in adherens junction organization. In heart
      microvascular endothelial cells, we identified a new member of the cadherin
      superfamily using polymerase chain reaction. The entire putative coding sequence
      was determined. Similarly to protocadherins, while the extracellular domain
      presented homology with other members of the cadherin superfamily, the
      intracellular region was unrelated either to cadherins or to any other known
      protein. We propose for this new protein the name of vascular endothelial
      cadherin-2. By Northern blot analysis, the mRNA was present only in cultured
      endothelial cell lines but not in other cell types such as NIH 3T3, Chinese
      hamster ovary, or L cells. In addition, mRNA was particularly abundant in highly
      vascularized organs such as lung or kidney. In endothelial cells and
      transfectants, this cadherin was unable to bind catenins and presented a weak
      association with the cytoskeleton. This new molecule shares some functional
      properties with VE-cadherin and other members of the cadherin family. In Chinese
      hamster ovary transfectants it promoted homotypic Ca2+ dependent aggregation and
      adhesion and clustered at intercellular junctions. However, in contrast to VE
      cadherin, it did not modify paracellular permeability, cell migration, and
      density-dependent cell growth. These observations suggest that different
      cadherins may promote homophilic cell-to-cell adhesion but that the functional
      consequences of this interaction depend on their binding to specific
      intracellular signaling/cytoskeletal proteins.

PMID- 9651351
TI  - Disruption of vitamin D receptor-retinoid X receptor heterodimer formation
      following ras transformation of human keratinocytes.
AB  - A partial resistance to the growth inhibitory influence of 1, 25-dihydroxyvitamin
      D3 is apparent when immortalized keratinocytes are transformed by the ras
      oncogene. The vitamin D receptor (VDR) was isolated, analyzed, and found to be
      identical in normal, immortalized, and ras-transformed keratinocytes.
      Subsequently, nuclear extracts from immortalized and ras-transformed
      keratinocytes were analyzed in gel mobility shift assays utilizing labeled
      vitamin D response elements or thyroid hormone response elements. A specific
      protein.DNA complex that was shown to contain VDR using an anti-VDR antibody was
      identified in both types of extracts; however, the addition of an anti-retinoid X
      receptor (RXR) antibody identified RXR in the complex of both normal and
      immortalized keratinocyte cell extracts, but not in ras-transformed
      keratinocytes. Furthermore, transfection of ras-transformed keratinocytes with
      wild-type human RXRalpha rescued VDR.RXR and thyroid hormone receptor.RXR
      complexes as demonstrated by a supershift in the presence of the anti-RXR
      antibody. Both cell lines were found to express RXRalpha message in equal
      amounts. Western blot analysis revealed that RXRalpha protein from ras
      transformed keratinocytes was indistinguishable from that from immortalized
      keratinocytes and from control cells. These results suggest a causal relationship
      between resistance to the growth inhibitory influences of 1,25-dihydroxyvitamin
      D3 and disruption of the VDR.RXR complex in malignant keratinocytes.

PMID- 9651352
TI  - A mechanism for calmodulin (CaM) trapping by CaM-kinase II defined by a family of
      CaM-binding peptides.
AB  - Autophosphorylation of Ca2+/calmodulin (CaM)-dependent protein kinase II (CaM
      kinase II) induces a striking >1,000-fold increase in its affinity for CaM, which
      has been called CaM trapping. Two peptides modeled after the CaM binding domain
      of CaM-kinase II were previously shown to kinetically resemble CaM binding to
      phosphorylated and dephosphorylated forms of the enzyme, thus providing a model
      system with which to define the molecular basis of CaM trapping. In this report,
      the specific contribution of each amino acid to the rates of association and
      dissociation, and the overall Kd of CaM binding to CaM-kinase II was determined
      using an overlapping peptide family, and a fluorescently labeled CaM. The
      association rate constants were similar for the entire family of peptides and
      ranged from 8 x 10(7) to 32 x 10(7) M-1 s-1. In contrast, the dissociation rate
      constants for the peptides varied by >3500-fold and ranged from 0.26 to 7 x 10(
      5) s-1. These rate constants yield overall Kd values for binding CaM to the
      peptides that range from 2 x 10(-9) M to 2 x 10(-13) M. Extending the low
      affinity CaM-binding peptide, CKII(296-312), to include 293Phe-Asn-Ala295
      provided the single largest contribution to the decreased dissociation rate
      constant, 1,300-fold. It was further shown using Ala-substituted peptides that
      the basic residues 296Arg-Arg-Lys299 were also essential for slow CaM
      dissociation; however, their contribution was realized only when 293Phe-Asn
      Ala295 were present. These results suggest a plausible model in which
      autophosphorylation of CaM-kinase II leads to a conformational change in the
      region of 293Phe-Asn-Ala295 which makes these residues accessible for binding to
      CaM. As a consequence of these changes, further CaM contacts with 296Arg-Arg
      Lys299 are established leading to high affinity CaM binding or "CaM trapping."

PMID- 9651353
TI  - Differential interactions of the C terminus and the cytoplasmic I-II loop of
      neuronal Ca2+ channels with G-protein alpha and beta gamma subunits. I. Molecular
      determination.
AB  - Interactions of G-protein alpha (Galpha) and beta gamma subunits (Gbeta gamma)
      with N- (alpha1B) and P/Q-type (alpha1A) Ca2+ channels were investigated using
      the Xenopus oocyte expression system. Gi3alpha was found to inhibit both N- and
      P/Q-type channels by receptor agonists, whereas Gbeta1 gamma2 was responsible for
      prepulse facilitation of N-type channels. L-type channels (alpha1C) were not
      regulated by Galpha or Gbeta gamma. For N-type, prepulse facilitation mediated
      via Gbeta gamma was impaired when the cytoplasmic I-II loop (loop 1) was deleted
      or replaced with the alpha1C loop 1. Galpha-mediated inhibitions were also
      impaired by substitution of the alpha1C loop 1, but only when the C terminus was
      deleted. For P/Q-type, by contrast, deletion of the C terminus alone diminished
      Galpha-mediated inhibition. Moreover, a chimera of L-type with the alpha1B loop 1
      gained Gbeta gamma-dependent facilitation, whereas an L-type chimera with the N-
      or P/Q-type C terminus gained Galpha-mediated inhibition. These findings provide
      evidence that loop 1 of N-type channels is a regulatory site for Gbeta gamma and
      the C termini of P/Q- and N-types for Galpha.

PMID- 9651354
TI  - Differential interactions of the C terminus and the cytoplasmic I-II loop of
      neuronal Ca2+ channels with G-protein alpha and beta gamma subunits. II. Evidence
      for direct binding.
AB  - The present study was designed to obtain evidence for direct interactions of G
      protein alpha (Galpha) and beta gamma subunits (Gbeta gamma) with N- (alpha1B)
      and P/Q-type (alpha1A) Ca2+ channels, using synthetic peptides and fusion
      proteins derived from loop 1 (cytoplasmic loop between repeat I and II) and the C
      terminus of these channels. For N-type, prepulse facilitation as mediated by
      Gbeta gamma was impaired when a synthetic loop 1 peptide was applied
      intracellularly. Receptor agonist-induced inhibition of N-type as mediated by
      Galpha was also impaired by the loop 1 peptide but only when applied in
      combination with a C-terminal peptide. For P/Q-type channels, by contrast, the
      Galpha-mediated inhibition was diminished by application of a C-terminal peptide
      alone. Moreover, in vitro binding analysis for N- and P/Q-type channels revealed
      direct interaction of Galpha with C-terminal fusion proteins as well as direct
      interaction of Gbeta gamma with loop 1 fusion proteins. These findings define
      loop 1 of N- and P/Q-type Ca2+ channels as an interaction site for Gbeta gamma
      and the C termini for Galpha.

PMID- 9651355
TI  - Crystal structure and mutational analysis of the Escherichia coli putrescine
      receptor. Structural basis for substrate specificity.
AB  - PotF protein is a periplasmic substrate-binding protein of the putrescine
      transport system in Escherichia coli. We have determined the crystal structure of
      PotF protein in complex with the substrate at 2.3-A resolution. The PotF molecule
      has dimensions of 54 x 42 x 30 A and consists of two similar globular domains.
      The PotF structure is reminiscent of other periplasmic receptors with a highest
      structural homology to another polyamine-binding protein, PotD. Putrescine is
      tightly bound in the deep cleft between the two domains of PotF through 12
      hydrogen bonds and 36 van der Waals interactions. The comparison of the PotF
      structure with that of PotD provides the insight into the differences in the
      specificity between the two proteins. The PotF structure, in combination with the
      mutational analysis, revealed the residues crucial for putrescine binding (Trp
      37, Ser-85, Glu-185, Trp-244, Asp-247, and Asp-278) and the importance of water
      molecules for putrescine recognition.

PMID- 9651356
TI  - Adenosine deaminase and A1 adenosine receptors internalize together following
      agonist-induced receptor desensitization.
AB  - A1 adenosine receptors (A1Rs) and adenosine deaminase (ADA; EC 3.5.4. 4) interact
      on the cell surface of DDT1MF-2 smooth muscle cells. The interaction facilitates
      ligand binding and signaling via A1R, but it is not known whether it has a role
      in homologous desensitization of A1Rs. Here we show that chronic exposure of
      DDT1MF-2 cells to the A1R agonist, N6-(R)-(phenylisopropyl)adenosine (R-PIA),
      caused a rapid aggregation or clustering of A1 receptor molecules on the cell
      membrane, which was enhanced by pretreatment with ADA. Colocalization between A1R
      and ADA occurred in the R-PIA-induced clusters. Interestingly, colocalization
      between A1R and ADA also occurred in intracellular vesicles after internalization
      of both protein molecules in response to R-PIA. Agonist-induced aggregation of
      A1Rs was mediated by phosphorylation of A1Rs, which was enhanced and accelerated
      in the presence of ADA. Ligand-induced second-messenger desensitization of A1Rs
      was also accelerated in the presence of exogenous ADA, and it correlated well
      with receptor phosphorylation. However, although phosphorylation of A1R returned
      to its basal state within minutes, desensitization continued for hours. The loss
      of cell-surface binding sites (sequestration) induced by the agonist was time
      dependent (t1/2= 10 +/- 1 h) and was accelerated by ADA. All of these results
      strongly suggest that ADA plays a key role in the regulation of A1Rs by
      accelerating ligand-induced desensitization and internalization and provide
      evidence that the two cell surface proteins internalize via the same endocytic
      pathway.

PMID- 9651357
TI  - Isolation and characterization of PAGE-1 and GAGE-7. New genes expressed in the
      LNCaP prostate cancer progression model that share homology with melanoma
      associated antigens.
AB  - The LNCaP progression model of human prostate cancer consists of lineage-related
      sublines that differ in their androgen sensitivity and metastatic potential. A
      differential display polymerase chain reaction was employed to evaluate mRNA
      expression differences between the LNCaP sublines in order to define the
      differences in gene expression between the androgen-sensitive, nontumorigenic
      LNCaP cell line and the androgen-insensitive, metastatic LNCaP sublines, C4-2 and
      C4-2B. An amplicon, BG16.21, was isolated that showed increased expression in the
      androgen-independent and metastatic LNCaP sublines, C4-2 and C4-2B. Hybridization
      screening of a lambda gt11 expression library with BG16.21 revealed two
      transcripts, both homologous to BG16.21 at the 3' end. A GenBankTM data base
      search using the GCG Wisconsin software package revealed the shorter
      approximately 600-bp transcript (designated GAGE-7) to be a new member of the
      GAGE family. The second approximately 700-bp transcript was a novel gene
      (designated PAGE-1, "prostate associated gene") with only 45% homology to GAGE
      gene family members. RNA blot analysis demonstrated that GAGE-7 mRNA was
      expressed at equal levels in all lineage related prostate cancer cell sublines,
      while PAGE-1 mRNA levels were elevated 5-fold in C4-2 and C4-2B as compared with
      LNCaP cells. Neither GAGE-7 nor PAGE-1 demonstrated any regulation by androgens
      in the prostate cancer cell lines used in this study. PAGE-1 and GAGE-7
      expression was found to be restricted to testes (high) and placenta (low) on
      human multiple tissue Northern blots. As GAGE/MAGE antigens were reported
      previously to be targets for tumor-specific cytotoxic lymphocytes in melanoma,
      these results suggest that PAGE-1 and GAGE-7 may be related to prostate cancer
      progression and may serve as potential targets for novel therapies.

PMID- 9651358
TI  - Structure-function analysis of FLT3 ligand-FLT3 receptor interactions using a
      rapid functional screen.
AB  - FLT3 ligand (FLT3L) stimulates primitive hematopoietic cells by binding to and
      activating the FLT3 receptor (FLT3R). We carried out a structure-activity study
      of human FLT3L in order to define the residues involved in receptor binding. We
      developed a rapid method to screen randomly mutagenized FLT3L using a FLT3R-Fc
      fusion protein to probe the relative binding activities of mutated ligand.
      Approximately 60,000 potential mutants were screened, and the DNA from 59 clones
      was sequenced. Thirty-one single amino acid substitutions at 24 positions of
      FLT3L either enhanced or reduced activity in receptor binding and cell
      proliferation assays. Eleven representative proteins were purified and analyzed
      for receptor affinity, specific activity, and physical properties. Receptor
      affinity and bioactivity were highly correlated. FLT3L affinity for receptor
      improved when four individual mutations that enhance FLT3L receptor affinity were
      combined in a single molecule. A model of FLT3L three-dimensional structure was
      generated based on sequence alignment and x-ray structure of macrophage colony
      stimulating factor. Most residues implicated in receptor binding are widely
      dispersed in the primary structure of FLT3L, yet they localize to a surface patch
      in the tertiary model. A mutation that maps to and is predicted to disrupt the
      proposed dimerization interface between FLT3L monomers exhibits a Stokes radius
      that is concentration-dependent, suggesting that this mutation disrupts the FLT3L
      dimer.

PMID- 9651359
TI  - Mutational analysis of the STAT6 SH2 domain.
AB  - The SH2 domain of the STAT family of transcription factors is essential for STAT
      binding to phosphorylated cytoplasmic domains of activated cytokine receptors.
      Furthermore, the same domain mediates dimerization of activated STAT monomers, a
      prerequisite for DNA binding by this family of proteins. To identify amino acid
      residues within the STAT protein that mediate these various interactions, we have
      carried out an extensive mutational analysis of the Stat6 SH2 domain. Recombinant
      proteins carrying C-terminal deletions or double alanine substitutions were
      expressed in mammalian and insect cells and assayed for DNA binding,
      transcription activation, tyrosine phosphorylation, and the ability to interact
      with a tyrosine-phosphorylated peptide derived from the interleukin-4 receptor
      signaling chain. From these studies, we have identified amino acids that are
      required for both DNA binding and interleukin-4 receptor interaction, as well as
      residues that when mutated impair only one of the two functions. Our results
      suggest that the structural homology between the SH2 domain of Stat6 and that of
      the distantly related Src protein may be higher than predicted on the basis of
      primary amino acid sequence comparisons. However, the two types of SH2 domains
      may differ at their C-terminal ends.

PMID- 9651360
TI  - Merbarone inhibits the catalytic activity of human topoisomerase IIalpha by
      blocking DNA cleavage.
AB  - Merbarone is a catalytic inhibitor of topoisomerase II that is in clinical trials
      as an anticancer agent. Despite the potential therapeutic value of this drug, the
      mechanism by which it blocks topoisomerase II activity has not been delineated.
      Therefore, to determine the mechanistic basis for the inhibitory action of
      merbarone, the effects of this drug on individual steps of the catalytic cycle of
      human topoisomerase IIalpha were assessed. Concentrations of merbarone that
      inhibited catalytic activity >/=80% had no effect on either enzyme.DNA binding or
      ATP hydrolysis. In contrast, the drug was a potent inhibitor of enzyme-mediated
      DNA scission (in the absence or presence of ATP), and the inhibitory profiles of
      merbarone for DNA cleavage and relaxation were similar. These data indicate that
      merbarone acts primarily by blocking topoisomerase II-mediated DNA cleavage.
      Merbarone inhibited DNA scission in a global (rather than site-specific) fashion
      but did not appear to intercalate into DNA or bind in the minor groove. Since the
      drug competed with etoposide (a cleavage-enhancing agent that binds directly to
      topoisomerase II), it is proposed that merbarone exerts its inhibitory effects
      through interactions with the enzyme and that the drug shares an interaction
      domain on topoisomerase II with cleavage-enhancing agents.

PMID- 9651361
TI  - Hepatitis C virus core protein interacts with heterogeneous nuclear
      ribonucleoprotein K.
AB  - Hepatitis C virus (HCV) core protein, a component of viral nucleocapsid, has been
      shown to modulate cellular and viral promoter activities. To identify potential
      cellular targets for HCV core protein, a human liver cDNA library was screened
      for core-interacting proteins using the yeast two-hybrid system. Among the
      proteins identified was heterogeneous nuclear ribonucleoprotein K (hnRNP K),
      which has been demonstrated to be a transcriptional regulator. The interaction of
      HCV core protein with hnRNP K was confirmed by glutathione S-transferase fusion
      protein binding assay, protein-protein blotting assay, and coimmunoprecipitation
      in vitro and in vivo. Additionally, these two proteins were shown to be partially
      colocalized in the nucleus. The hnRNP K-binding site in HCV core protein was
      mapped to the region from amino acid residues 25-91, a hydrophilic area near the
      N terminus. The HCV core protein-binding domain was located within amino acid
      residues 250 to 392, which contain the three proline-rich domains, of hnRNP K.
      Furthermore, HCV core protein relieved the suppression effect of hnRNP K on the
      activity of the human thymidine kinase gene promoter. The specific binding of HCV
      core protein to hnRNP K suggests that multiple functions of hnRNP K may be
      disrupted by the core protein during HCV infection and thus explains, in part,
      the pathogenesis of HCV.

PMID- 9651362
TI  - Platelet-activating factor receptor activation. An initiator step in HIV-1
      neuropathogenesis.
AB  - Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous
      system results in neuronal apoptosis. Activated HIV-1-infected monocytes secrete
      high levels of the proinflammatory cytokine tumor necrosis factor-alpha (TNF
      alpha) and the phospholipid mediator platelet-activating factor (PAF). TNF-alpha
      and PAF are elevated in the central nervous system of patients with HIV-1
      associated dementia. We now demonstrate that conditioned media from activated HIV
      1-infected monocytes induces neuronal apoptosis, which can be prevented by co
      incubation with PAF acetylhydrolase, the enzyme that catabolizes PAF in the
      central nervous system. Preceding apoptosis is a TNF-alpha-induced increase in
      neuronal ceramide levels. TNF-alpha-mediated neuronal apoptosis can also be
      blocked by co-incubation with PAF acetylhydrolase, or a PAF receptor antagonist.
      Blocking pathologic activation of PAF receptors may therefore be a pivotal step
      in the treatment of HIV-1-associated dementia.

PMID- 9651363
TI  - A type I peritrophic matrix protein from the malaria vector Anopheles gambiae
      binds to chitin. Cloning, expression, and characterization.
AB  - Upon feeding, mosquito midguts secrete the peritrophic matrix (PM), an
      extracellular chitin-containing envelope that completely surrounds the blood
      meal. Because the malaria parasite must cross the PM to complete its life cycle
      in the mosquito, the PM is a potential barrier for malaria transmission. By
      antibody screening of an expression library we have identified and partially
      characterized a cDNA encoding a putative PM protein, termed Anopheles gambiae
      adult peritrophin 1 (Ag-Aper1). Ag-Aper1 is the first cloned PM gene from a
      disease vector. Northern analysis detected an abundant Ag-Aper1 transcript only
      in the adult gut, and not in any other tissues or at any other stages of
      development. The predicted amino acid sequence indicates that it has two tandem
      chitin-binding domains that share high sequence similarity with each other and
      also with the chitin-binding domain of an adult gut-specific chitinase from the
      same organism. The presumed ability of Ag-Aper1 to bind chitin was verified by a
      functional assay with the baculovirus-expressed recombinant protein. Ag-Aper1 did
      bind to chitin but not to cellulose, indicating that Ag-Aper1 binds chitin
      specifically. The double chitin-binding domain organization of Ag-Aper1 suggests
      that each protein molecule is able to link two chitin polymer chains. Hence, this
      protein is likely to act as a molecular linker that connects PM chitin fibrils
      into a three-dimensional network.

PMID- 9651364
TI  - Subunit interactions within an expressed regulatory domain of chicken skeletal
      myosin. Location of the NH2 terminus of the regulatory light chain by
      fluorescence resonance energy transfer.
AB  - The regulatory domain (RD), or neck region of the myosin head, consists of two
      classes of light chains that stabilize an alpha-helical segment of the heavy
      chain. RD from chicken skeletal muscle myosin was prepared in Escherichia coli by
      coexpression of a 9-kDa heavy chain fragment with the essential light chain.
      Recombinant regulatory light chain (RLC), wild type or mutant, was added
      separately to reconstitute the complex. The affinity of RD for divalent cations
      was determined by measuring the change in fluorescence of a pair of heavy chain
      tryptophans upon addition of calcium or magnesium. The complex bound divalent
      cations with high affinity, similar to the association constants determined for
      native myosin. The intrinsic fluorescence of the tryptophans could be used as a
      donor to measure the fluorescence resonance energy transfer distance to a single
      labeled cysteine engineered at position 2 on RLC. Dansylated Cys2 could also
      serve as a donor by preparing RLC with a second cysteine at position 79 which was
      labeled with an acceptor probe. These fluorescence resonance energy transfer
      distances (24-30 A), together with a previous measurement between Cys2 and Cys155
      (Wolff-Long, V. L., Tao, T., and Lowey, S. (1995) J. Biol. Chem. 270, 31111
      31118) suggest a location for the NH2 terminus of RLC that appears to preclude a
      direct interaction between the phosphorylatable serine and specific residues in
      the COOH-terminal domain.

PMID- 9651365
TI  - Isoenzymes of pyruvate dehydrogenase phosphatase. DNA-derived amino acid
      sequences, expression, and regulation.
AB  - Pyruvate dehydrogenase phosphatase (PDP) is one of the few mammalian phosphatases
      residing within the mitochondrial matrix space. It is responsible for
      dephosphorylation and reactivation of the pyruvate dehydrogenase complex (PDC)
      and, by this means, is intimately involved in the regulation of utilization of
      carbohydrate fuels in mammals. PDP is a dimeric enzyme consisting of catalytic
      and regulatory subunits. The catalytic subunit of PDP is a Mg2+-dependent enzyme
      homologous to the cytosolic phosphatases of the 2C family. In the present study,
      we isolated two cDNAs encoding for mitochondrial phosphatases. The first cDNA is
      highly homologous to the previously identified cDNA encoding for the catalytic
      subunit of PDP (PDP1). The second cDNA encodes a previously unknown catalytic
      subunit of PDP (PDP2). The new phosphatase, expressed as the recombinant protein
      in Escherichia coli, shows strict substrate specificity toward PDC and does not
      use phosphorylated branched chain alpha-ketoacid dehydrogenase as substrate. Like
      PDP1, PDP2 is a Mg2+-dependent enzyme, but its sensitivity to Mg2+ ions is almost
      10-fold lower than that of PDP1. In contrast to PDP1, PDP2 is not regulated by
      Ca2+ ions. Instead, it is sensitive to the biological polyamine spermine, which,
      in turn, has no effect on the enzymatic activity of PDP1. Western blot analysis
      of PDP extracted from mitochondria isolated from liver and skeletal muscle
      revealed that PDP1 is predominantly expressed in mitochondria from skeletal
      muscle, whereas PDP2 is much more abundant in the liver rather than muscle
      mitochondria. Both isoenzymes are expressed in mitochondria from 3T3-L1
      adipocytes, but the level of expression of PDP2 is considerably higher. These
      observations are consistent with previous findings on the enzymatic parameters of
      PDP in adipose tissue. Thus, our results provide the first evidence that there
      are at least two isoenzymes of PDP in mammals that are different with respect to
      tissue distribution and kinetic parameters and, therefore, are likely to be
      different functionally.

PMID- 9651366
TI  - Molecular cloning, chromosomal localization, tissue distribution, and functional
      expression of the human pancreatic sodium bicarbonate cotransporter.
AB  - We report the cloning, sequence analysis, tissue distribution, functional
      expression, and chromosomal localization of the human pancreatic sodium
      bicarbonate cotransport protein (pancreatic NBC (pNBC)). The transporter was
      identified by searching the human expressed sequence tag data base. An I.M.A.G.E.
      clone W39298 was identified, and a polymerase chain reaction probe was generated
      to screen a human pancreas cDNA library. pNBC encodes a 1079-residue polypeptide
      that differs at the N terminus from the recently cloned human sodium bicarbonate
      cotransporter isolated from kidney (kNBC) (Burnham, C. E., Amlal, H., Wang, Z.,
      Shull, G. E., and Soleimani, M. (1997) J. Biol. Chem. 272, 19111-19114). Northern
      blot analysis using a probe specific for the N terminus of pNBC revealed an
      approximately 7.7-kilobase transcript expressed predominantly in pancreas, with
      less expression in kidney, brain, liver, prostate, colon, stomach, thyroid, and
      spinal chord. In contrast, a probe to the unique 5' region of kNBC detected an
      approximately 7.6-kilobase transcript only in the kidney. In situ hybridization
      studies in pancreas revealed expression in the acini and ductal cells. The gene
      was mapped to chromosome 4q21 using fluorescent in situ hybridization. Expression
      of pNBC in Xenopus laevis oocytes induced sodium bicarbonate cotransport. These
      data demonstrate that pNBC encodes the sodium bicarbonate cotransporter in the
      mammalian pancreas. pNBC is also expressed at a lower level in several other
      organs, whereas kNBC is expressed uniquely in kidney.

PMID- 9651367
TI  - A role for RalGDS and a novel Ras effector in the Ras-mediated inhibition of
      skeletal myogenesis.
AB  - Oncogenic Ras inhibits the differentiation of skeletal muscle cells through the
      activation of multiple downstream signaling pathways, including a Raf-dependent,
      mitogen-activated or extracellular signal-regulated kinase kinase/mitogen
      activated protein kinase (MEK/MAPK)-independent pathway. Here we report that a
      non-Raf binding Ras effector-loop variant (H-Ras G12V,E37G), which retains
      interaction with the Ral guanine nucleotide dissociation stimulator (RalGDS),
      inhibits the conversion of MyoD-expressing C3H10T1/2 mouse fibroblasts to
      skeletal muscle. We show that H-Ras G12V,E37G, RalGDS, and the membrane-localized
      RalGDS CAAX protein inhibit the activity of alpha-actin-Luc, a muscle-specific
      reporter gene containing a necessary E-box and serum response factor (SRF)
      binding site, while a RalGDS protein defective for Ras interaction has no effect
      on alpha-actin-Luc transcription. H-Ras G12V,E37G does not activate endogenous
      MAPK, but does increase SRF-dependent transcription. Interestingly, RalGDS,
      RalGDS CAAX, and RalA G23V inhibit H-Ras G12V, E37G-induced expression of an SRF
      regulated reporter gene, demonstrating that signaling through RalGDS does not
      duplicate the action of H-Ras G12V,E37G in this system. As additional evidence
      for this, we show that H-Ras G12V,E37G inhibits the expression of troponin I-Luc,
      an SRF-independent muscle-specific reporter gene, whereas RalGDS and RalGDS CAAX
      do not. Although our studies show that signaling through RalGDS can interfere
      with the expression of reporter genes dependent on SRF activity (including alpha
      actin-Luc), our studies also provide strong evidence that an additional signaling
      molecule(s) activated by H-Ras G12V,E37G is required to achieve the complete
      inhibition of the myogenic differentiation program.

PMID- 9651368
TI  - A hinge at the central helix of the regulatory light chain of myosin is critical
      for phosphorylation-dependent regulation of smooth muscle myosin motor activity.
AB  - The motor function of smooth muscle myosin is activated by phosphorylation of the
      regulatory light chain (RLC) at Ser19. However, the molecular mechanism by which
      the phosphorylation activates the motor function is not yet understood. In the
      present study, we focused our attention on the role of the central helix of RLC
      for regulation. The flexible region at the middle of the central helix (Gly95
      Pro98) was substituted or deleted to various extents, and the effects of the
      deletion or substitution on the regulation of the motor activity of myosin were
      examined. Deletion of Gly95-Asp97, Gly95-Thr96, or Thr96-Asp97 decreased the
      actin-translocating activity of myosin a little, but the phosphorylation
      dependent regulation of the motor activity was not disrupted. In contrast, the
      deletion of Gly95-Pro98 of RLC completely abolished the actin translocating
      activity of phosphorylated myosin. However, the unregulated myosin long
      subfragment 1 containing this RLC mutant showed motor activity the same as that
      containing the wild type RLC. Since long subfragment 1 motor activity is
      unregulated by phosphorylation, i.e. constitutively active, these results suggest
      that the deletion of these residues at the central helix of RLC disrupts the
      phosphorylation-mediated activation mechanism but not the motor function of
      myosin itself. On the other hand, the elimination of Pro98 or substitution of
      Gly95-Pro98 by Ala resulted in the activation of actin translocating activity of
      dephosphorylated myosin, whereas it did not affect the motor activity of
      phosphorylated myosin. Together, these results clearly indicate the importance of
      the hinge at the central helix of RLC on the phosphorylation-mediated regulation
      of smooth muscle myosin.

PMID- 9651369
TI  - The death inhibitory molecules CED-9 and CED-4L use a common mechanism to inhibit
      the CED-3 death protease.
AB  - The apoptotic machinery of Caenorhabditis elegans includes three core interacting
      components: CED-3, CED-4, and CED-9. CED-3 is a death protease composed of a
      prodomain and a protease domain. CED-4 is a P-loop-containing, nucleotide-binding
      molecule that complexes with the single polypeptide zymogen form of CED-3,
      promoting its activation by autoprocessing. CED-9 blocks death by complexing with
      CED-4 and suppressing its ability to promote CED-3 activation. A naturally
      occurring alternatively spliced form of CED-4 that contains an insertion within
      the nucleotide-binding region (CED-4L) functions as a dominant negative inhibitor
      of CED-3 processing and attenuates cell death. Domain mapping studies revealed
      that distinct regions within CED-4 bind to the CED-3 prodomain and protease
      domain. Importantly, the CED-4 P-loop was involved in prodomain binding.
      Disruption of P-loop geometry because of mutation of a critical lysine (K165R) or
      insertional inactivation (CED-4L) abolished prodomain binding. Regardless, K165R
      and CED-4L still retained CED-3 binding through the protease domain but were
      unable to initiate CED-3 processing. Therefore, the P-loop-prodomain interaction
      is critical for triggering CED-4-mediated CED-3 processing. Underscoring the
      importance of this interaction was the finding that CED-9 contacted the P-loop
      and selectively inhibited its interaction with the CED-3 prodomain. These results
      provide a simple mechanism for how CED-9 functions to block CED-4-mediated CED-3
      processing and cell death.

PMID- 9651370
TI  - Interaction of eye protein kinase C and INAD in Drosophila. Localization of
      binding domains and electrophysiological characterization of a loss of
      association in transgenic flies.
AB  - Drosophila eye-specific protein kinase C (eye-PKC) is involved in light
      adaptation and deactivation. eye-PKC, NORPA (phospholipase Cbeta), and transient
      receptor-potential (TRP) (calcium channel) are integral components of a signal
      transduction complex organized by INAD, a protein containing five PDZ domains. We
      previously demonstrated the direct association between the third PDZ domain of
      INAD with TRP in addition to the carboxyl-terminal half of INAD with the last
      three residues of NORPA. In this work, the molecular interaction between eye-PKC
      and INAD is defined via the yeast two-hybrid and ligand overlay assays. We show
      that the second PDZ domain of INAD interacts with the last three residues in the
      carboxyl-terminal tail of eye-PKC, Thr-Ile-Ile. The association between eye-PKC
      and INAD is disrupted by an amino acid substitution (Ile-700 to Asp) at the final
      residue of eye-PKC. In flies lacking endogenous eye-PKC (inaCp215), normal visual
      physiology is restored upon expression of wild-type eye-PKC, whereas the eye
      PKCI700D mutant is completely inactive. Flies homozygous for inaCp209 and
      InaDp215, a mutation that causes a loss of the INAD-TRP association, were
      generated. These double mutants display a more severe response inactivation than
      either of the single mutants. Based on these findings, we conclude that the in
      vivo activity of eye-PKC depends on its association with INAD and that the
      sensitivity of photoreceptors is cooperatively regulated by the presence of both
      eye-PKC and TRP in the signaling complex.

PMID- 9651371
TI  - Inhibition of hGrb10 binding to the insulin receptor by functional domain
      mediated oligomerization.
AB  - hGrb10 is a newly identified Src homology 2 (SH2) and pleckstrin homology (PH)
      domain-containing protein that binds to autophosphorylated receptor tyrosine
      kinases, including the insulin and insulin-like growth factor receptors. To
      identify potential downstream proteins that interact with hGrb10, we screened a
      yeast two-hybrid cDNA library using the full-length hGrb10gamma as bait. A
      fragment of hGrb10, which included the IPS (insert between the PH and SH2 domain)
      and the SH2 domains, was found to bind with high affinity to the full-length
      protein. The interaction between the IPS/SH2 domain and the full-length hGrb10
      was further confirmed by in vitro glutathione S-transferase fusion protein
      binding studies. Gel filtration assays showed that hGrb10 underwent
      tetramerization in mammalian cells. The interaction involved at least two
      functional domains, the IPS/SH2 region and the PH domain, both of which
      interacted with the NH2-terminal amino acid sequence of hGrb10gamma (hGrb10gamma
      DeltaC, residues 4-414). Competition studies showed that hGrb10gamma DeltaC
      inhibited the binding of hGrb10 to the tyrosine-phosphorylated insulin receptor,
      suggesting that this region may play a regulatory role in hGrb10/insulin receptor
      interaction. We present a model for hGrb10 tetramerization and its potential role
      in receptor tyrosine kinase signal transduction.

PMID- 9651372
TI  - Acylamino acid-releasing enzyme from the thermophilic archaeon Pyrococcus
      horikoshii.
AB  - When the genome of the thermophilic archaeon Pyrococcus horikoshii was sequenced,
      a gene homologous to the mammalian gene for an acylamino acid-releasing enzyme
      (EC 3.4.19.1) was found in which the enzyme's proposed active residues were
      conserved. The P. horikoshii gene comprised an open reading frame of 1,896 base
      pairs with an ATG initiation codon and a TAG termination codon, encoding a 72,390
      Da protein of 632 amino acid residues. This gene was overexpressed in Escherichia
      coli with the pET vector system, and the resulting enzyme showed the anticipated
      amino-terminal sequence and high hydrolytic activity for acylpeptides. This
      enzyme was concluded to be the first acylamino acid-releasing enzyme from an
      organism other than a eukaryotic cell. The existence of the enzyme in archaea
      suggests that the mechanisms of protein degradation or initiation of protein
      synthesis or both in archaea may be similar to those in eukaryotes. The enzyme
      was stable at 90 degreesC, with its optimum temperature over 90 degreesC. The
      specific activity of the enzyme increased 7-14-fold with heat treatment,
      suggesting the modification of the enzyme's structure for optimal hydrolytic
      activity by heating. This enzyme is expected to be useful for the removal of
      Nalpha-acylated residues in short peptide sequence analysis at high temperatures.

PMID- 9651373
TI  - SNAP-23 requirement for transferrin recycling in Streptolysin-O-permeabilized
      Madin-Darby canine kidney cells.
AB  - Fusion of recycling and transcytotic vesicles with the apical and basolateral
      plasma membrane domains of Madin-Darby canine kidney (MDCK) cells requires the N
      ethylmaleimide-sensitive factor and is sensitive to botulinum neurotoxin serotype
      E (BoNT/E). BoNT/E is thought to selectively proteolyze the 25,000-dalton
      synaptosomal associated protein (SNAP-25), a protein found in neurons or cells of
      neuroendocrine origin. However, SNAP-25 is not found in MDCK cells. One possible
      target for BoNT/E in MDCK cells is SNAP-23, a newly described SNAP-25 homolog
      that is found in several organs including kidney. Currently, the function of SNAP
      23 is unknown. We have reconstituted transferrin recycling in permeabilized MDCK
      cells to assess the role of SNAP-23 in the endocytic traffic of this protein. We
      find that: (i) SNAP-23 is expressed in MDCK cells and is found both at the
      basolateral plasma membrane and associated with apical and basolateral vesicles,
      (ii) canine SNAP-23 is cleaved by BoNT/E, (iii) transferrin recycling is N
      ethylmaleimide-sensitive factor-dependent and BoNT/E-sensitive, and (iv) addition
      of either exogenous SNAP-23 or anti-SNAP-23 antibodies inhibits ligand recycling.
      Our observations suggest that SNAP-23 may be required for fusion of recycling
      vesicles with the basolateral membrane of polarized MDCK cells.

PMID- 9651374
TI  - Role of tyrosine kinases in induction of the c-jun proto-oncogene in irradiated B
      lineage lymphoid cells.
AB  - Exposure of B-lineage lymphoid cells to ionizing radiation induces an elevation
      of c-jun proto-oncogene mRNA levels. This signal is abrogated by protein-tyrosine
      kinase (PTK) inhibitors, indicating that activation of an as yet unidentified PTK
      is mandatory for radiation-induced c-jun expression. Here, we provide
      experimental evidence that the cytoplasmic tyrosine kinases BTK, SYK, and LYN are
      not required for this signal. Lymphoma B-cells rendered deficient for LYN, SYK,
      or both by targeted gene disruption showed increased c-jun expression levels
      after radiation exposure, but the magnitude of the stimulation was lower than in
      wild-type cells. Thus, these PTKs may participate in the generation of an optimal
      signal. Notably, an inhibitor of JAK-3 (Janus family kinase-3) abrogated
      radiation-induced c-jun activation, prompting the hypothesis that a chicken
      homologue of JAK-3 may play a key role in initiation of the radiation-induced c
      jun signal in B-lineage lymphoid cells.

PMID- 9651375
TI  - GTPase activating specificity of RGS12 and binding specificity of an
      alternatively spliced PDZ (PSD-95/Dlg/ZO-1) domain.
AB  - Regulator of G-protein signaling (RGS) proteins increase the intrinsic guanosine
      triphosphatase (GTPase) activity of G-protein alpha subunits in vitro, but how
      specific G-protein-coupled receptor systems are targeted for down-regulation by
      RGS proteins remains uncharacterized. Here, we describe the GTPase specificity of
      RGS12 and identify four alternatively spliced forms of human RGS12 mRNA. Two
      RGS12 isoforms of 6.3 and 5.7 kilobases (kb), encoding both an N-terminal PDZ
      (PSD-95/Dlg/ZO-1) domain and the RGS domain, are expressed in most tissues, with
      highest levels observed in testis, ovary, spleen, cerebellum, and caudate
      nucleus. The 5.7-kb isoform has an alternative 3' end encoding a putative C
      terminal PDZ domain docking site. Two smaller isoforms, of 3.1 and 3.7 kb, which
      lack the PDZ domain and encode the RGS domain with and without the alternative 3'
      end, respectively, are most abundantly expressed in brain, kidney, thymus, and
      prostate. In vitro biochemical assays indicate that RGS12 is a GTPase-activating
      protein for Gi class alpha subunits. Biochemical and interaction trap experiments
      suggest that the RGS12 N terminus acts as a classical PDZ domain, binding
      selectively to C-terminal (A/S)-T-X-(L/V) motifs as found within both the
      interleukin-8 receptor B (CXCR2) and the alternative 3' exon form of RGS12. The
      presence of an alternatively spliced PDZ domain within RGS12 suggests a mechanism
      by which RGS proteins may target specific G-protein-coupled receptor systems for
      desensitization.

PMID- 9651376
TI  - Cloning and characterization of a novel binding factor (GMEB-2) of the
      glucocorticoid modulatory element.
AB  - The 21-base pair glucocorticoid modulatory element (GME) of the rat tyrosine
      aminotransferase gene is the only cis-acting element known to modulate the
      transcriptional activity of receptors bound to glucocorticoid response elements.
      Specifically, the GME increases the activity of complexes bound both by
      physiological concentrations of glucocorticoids, due to a left shift in the dose
      response curve, and by saturating concentrations of anti-glucocorticoids. For
      this reason, the nuclear protein(s) that has been demonstrated to bind to the GME
      is of major interest as a possible transcription factor with hitherto undescribed
      properties. Subsequent studies indicated that not one but two proteins of 88 and
      67 kDa (= GMEB-1 and -2, respectively) formed a heteromeric complex with double
      stranded GME oligonucleotides in gel shift assays and participated in the
      expression of GME activity (Oshima, H., Szapary, D., and Simons, S. S., Jr.
      (1995) J. Biol. Chem. 270, 21893-21910). Here, we report the use of polymerase
      chain reaction of degenerate oligonucleotides and 5'- and 3'-rapid amplification
      of cDNA ends to clone two cDNAs of 2. 0 and 1.9 kilobase pairs that probably
      result from alternative splicing. Both cDNAs encoded open reading frames
      containing all four previously sequenced peptides. The longer 2.0-kilobase pair
      cDNA encoded an open reading frame for an acidic, 529-amino acid protein and
      afforded a major 67-kDa and a minor 58-kDa protein after in vitro
      transcription/translation. Both proteins were recognized by a mono-epitopic
      antibody raised against a peptide of GMEB-2. The in vitro translated protein
      bound to GME DNA in gel shift assays. However, the binding to GME DNA increased
      markedly after mixing with authentic GMEB-1 to give a gel-shifted complex that
      was similar to that derived from HTC cell cytosol. GMEB-2 shares a unique domain
      (KDWKR) with proteins derived from diverse organisms as follows: Drosophila (DEAF
      I), rat (Suppressin), and Caenorhabditis elegans (three unknown open reading
      frames). Collectively, these data suggest that the 67-kDa GMEB-2 not only is an
      important factor for the modulation of glucocorticoid receptor bound to
      glucocorticoid response elements but also may belong to a novel family of
      transcription factors.

PMID- 9651377
TI  - Ceramides are bound to structural proteins of the human foreskin epidermal
      cornified cell envelope.
AB  - An important component of barrier function in human epidermis is contributed by
      ceramides that are bound by ester linkages to undefined proteins of the cornified
      cell envelope (CE). In this paper, we have examined the protein targets for the
      ceramide attachment. By partial saponification of isolated foreskin epidermal CEs
      followed by limited proteolysis, we have recovered several lipopeptides.
      Biochemical and mass spectroscopic characterization revealed that all contained
      near stoichiometric amounts of ceramides of masses ranging from about 690 to 890
      atomic mass units, of which six quantitatively major species were common. The
      array of ceramides was similar to that obtained from pig skin, the composition of
      which is known, thereby providing strong indirect data for their fatty acid and
      sphingosine compositions. The recovered peptides accounted for about 20% of the
      total foreskin CE ceramides. By amino acid sequencing, about 35% of the peptides
      were derived from ancestral glutamine-glutamate-rich regions of involucrin, an
      important CE structural protein. Another 18% derived from rod domain sequences of
      periplakin and envoplakin, which are also known or suspected CE proteins. Other
      peptides were too short for unequivocal identification. Together, these data
      indicate that involucrin, envoplakin, periplakin, and possibly other structural
      proteins serve as substrates for the attachment of ceramides by ester linkages to
      the CE for barrier function in human epidermis.

PMID- 9651378
TI  - Insulin-like growth factor I (IGF-I)-stimulated pancreatic beta-cell growth is
      glucose-dependent. Synergistic activation of insulin receptor substrate-mediated
      signal transduction pathways by glucose and IGF-I in INS-1 cells.
AB  - Nutrients and certain growth factors stimulate pancreatic beta-cell mitogenesis,
      however, the appropriate mitogenic signal transduction pathways have not been
      defined. In the glucose-sensitive pancreatic beta-cell line, INS-1, it was found
      that glucose (6-18 mM) independently increased INS-1 cell proliferation (>20-fold
      at 15 mM glucose). Insulin-like growth factor I (IGF-I)-induced INS-1 cell
      proliferation was glucose-dependent only in the physiologically relevant
      concentration range (6-18 mM glucose). The combination of IGF-I and glucose was
      synergistic, increasing INS-1 cell proliferation >50-fold at 15 mM glucose + 10
      nM IGF-I. Glucose metabolism and phosphatidylinositol 3'-kinase (PI 3'-kinase)
      activation were necessary for both glucose and IGF-I-stimulated INS-1 cell
      proliferation. IGF-I and 15 mM glucose increased tyrosine phosphorylation
      mediated recruitment of Grb2/mSOS and PI 3'-kinase to IRS-2 and pp60. Glucose and
      IGF-I also induced Shc association with Grb2/mSOS. Glucose (3-18 mM) and IGF-I,
      independently of glucose, activated mitogen-activated protein kinase but this did
      not correlate with IGF-I-induced beta-cell proliferation. In contrast, p70(S6K)
      was activated with increasing glucose concentration (between 6 and 18 mM), and
      potentiated by IGF-I in the same glucose concentration range which correlated
      with INS-1 cell proliferation rate. Thus, glucose and IGF-I-induced beta-cell
      proliferation were mediated via a signaling mechanism that was facilitated by
      mitogen-activated protein kinase but dependent on IRS-mediated induction of PI 3'
      kinase activity and downstream activation of p70(S6K). The glucose dependence of
      IGF-I mediated INS-1 cell proliferation emphasizes beta-cell signaling mechanisms
      are rather unique in being tightly linked to glycolytic metabolic flux.

PMID- 9651379
TI  - Expression and characterization of a 70-kDa fragment of the insulin receptor that
      binds insulin. Minimizing ligand binding domain of the insulin receptor.
AB  - In order to characterize regions of the insulin receptor that are essential for
      ligand binding and possibly identify a smaller insulin-binding fragment of the
      receptor, we have used site-directed mutagenesis to construct a series of insulin
      receptor deletion mutants. From 112 to 246 amino acids were deleted from the
      alpha-subunit region comprising amino acids 469-729. The receptor constructs were
      expressed as soluble insulin receptor IgG fusion proteins in baby hamster kidney
      cells and were characterized in binding assays by immunoblotting and chemical
      cross-linking with radiolabeled insulin. The shortest receptor fragment
      identified was a free monomeric alpha-subunit deleted of amino acids 469-703 and
      718-729 (exon 11); the mass of this receptor fragment was found by mass
      spectrometry to be 70 kDa. This small insulin receptor fragment bound insulin
      with an affinity (Kd) of 4.4 nM, which is similar to what was found for the full
      length ectodomain of the insulin receptor (5.0 nM). Cross-linking experiments
      confirmed that the 70-kDa receptor fragment specifically bound insulin. In
      summary we have minimized the insulin binding domain of the insulin receptor by
      identifying a 70-kDa fragment of the ectodomain that retains insulin binding
      affinity making this an interesting candidate for detailed structural analysis.

PMID- 9651380
TI  - Adrenomedullin gene expression is developmentally regulated and induced by
      hypoxia in rat ventricular cardiac myocytes.
AB  - Adrenomedullin is a recently discovered hypotensive peptide that is expressed in
      a variety of cell and tissue types. Using the technique of differential display,
      the adrenomedullin gene was observed to be differentially expressed in developing
      rat heart. Reverse transcription-polymerase chain reaction analysis revealed that
      the level of adrenomedullin mRNA was significantly higher in adult ventricular
      cardiac muscle as compared with embryonic day 17 ventricular cardiac muscle.
      Adrenomedullin receptor mRNA was constitutively expressed throughout development
      of the ventricular heart. Two potential hypoxia-inducible factor-1 (HIF-1)
      consensus binding sites were identified in the mouse adrenomedullin promoter at 
      1095 and -770 nucleotides from the transcription start site. Exposure of cultured
      adult rat ventricular cardiac myocytes to hypoxia (1% O2) resulted in a
      significant, time-dependent increase in adrenomedullin mRNA levels. Transfection
      studies revealed that the 5'-flanking sequence of adrenomedullin was capable of
      mediating a hypoxia-inducible increase in transcription. Mutation of the putative
      HIF-1 consensus binding sites revealed that the major regulatory sequence that
      mediates the hypoxia-inducible transcriptional response is located at -1095.
      These data demonstrate that the adrenomedullin gene is developmentally regulated
      in ventricular cardiomyocytes, that adrenomedullin transcription can be induced
      by hypoxia, and that this response is primarily mediated by HIF-1 consensus sites
      in the adrenomedullin promoter.

PMID- 9651381
TI  - Apolipoprotein(a) synthesis and secretion from hepatoma cells is coupled to
      triglyceride synthesis and secretion.
AB  - Apolipoprotein(a) (apo(a)) is synthesized and secreted from liver cells and
      represents one of the two major protein components of the atherogenic
      lipoprotein, Lp(a). Little is known, however, of the factors that regulate the
      secretion of this protein. We have undertaken an analysis of the response to
      oleate supplementation in stable clones of HepG2 and McA-RH7777 cells expressing
      either a 6 K-IV or 17 K-IV isoform of apo(a). These cell lines were examined by
      pulse-chase analysis and each demonstrated an increase (range 2-6-fold) in apo(a)
      secretion following supplementation with 0.8 mM oleate. Microsomal membranes,
      prepared from HepG2 cells expressing a 6 K-IV apo(a) isoform, demonstrated that
      oleate supplementation increased the apparent protection of apo(a) from protease
      digestion, suggesting that alterations in the translocation efficiency of apo(a)
      may accompany the addition of oleate. Cells incubated with brefeldin A
      demonstrated increased recovery of the precursor form of apo(a) with oleate
      supplementation, suggesting that alterations in post-translational degradation
      may also contribute to the observed increase in apo(a) secretion following oleate
      addition. To further characterize the oleate-dependent increase in apo(a)
      secretion, cells were incubated with an inhibitor of the microsomal triglyceride
      transfer protein. These experiments demonstrated a dose-dependent decrease in
      apo(a) secretion from both cell lines. Furthermore, addition of either the
      microsomal triglyceride transfer protein inhibitor or triacsin C, an inhibitor of
      acyl-CoA synthase, completely abrogated the oleate-dependent increase in apo(a)
      secretion. Taken together, these data provide evidence that apo(a) secretion from
      hepatoma cells may be linked to elements of cellular triglyceride assembly and
      secretion.

PMID- 9651382
TI  - Second-site cleavage in sterol regulatory element-binding protein occurs at
      transmembrane junction as determined by cysteine panning.
AB  - In response to sterol deprivation, two sequential proteolytic cleavages release
      the NH2-terminal fragments of sterol regulatory element-binding proteins (SREBPs)
      from cell membranes. The fragments translocate to the nucleus where they activate
      genes involved in cholesterol and fatty acid metabolism. The SREBPs are bound to
      membranes in a hairpin fashion. The NH2-terminal and COOH-terminal domains face
      the cytoplasm, separated by two membrane spanning segments and a short lumenal
      loop. The first cleavage occurs at Site-1 in the lumenal loop. The NH2-terminal
      fragment is then released by cleavage at Site-2, which is believed to lie within
      the first transmembrane segment. Here, we use a novel cysteine panning method to
      identify the second cleavage site (Site-2) in human SREBP-2 as the Leu484-Cys485
      bond that lies at the junction between the cytoplasmic NH2-terminal fragment and
      the first transmembrane segment. We transfected cells with cDNAs encoding fusion
      proteins with single cysteine residues at positions to the NH2-terminal and COOH
      terminal sides of cysteine 485. The NH2-terminal fragments were tested for
      susceptibility to modification with Nalpha-(3-maleimidylpropionyl)biocytin, which
      attaches a biotin group to cysteine sulfhydryls. Cysteines to the NH2-terminal
      side of cysteine 485 were retained on the NH2-terminal fragment, but cysteines to
      the COOH-terminal side of leucine 484 were lost. Leucine 484 is three residues to
      the COOH-terminal side of the tetrapeptide Asp-Arg-Ser-Arg, which immediately
      precedes the first transmembrane segment and is required for Site-2 cleavage.

PMID- 9651383
TI  - Transactivation of the human apolipoprotein CII promoter by orphan and ligand
      dependent nuclear receptors. The regulatory element CIIC is a thyroid hormone
      response element.
AB  - The regulatory elements CIIC (-159/-116) and CIIB (-102/-81) of the
      apolipoprotein CII (apoCII) promoter have distinct specificities for orphan
      nuclear receptors (Vorgia, P., Zannis, V. I., and Kardassis, D. (1998) J. Biol.
      Chem. 273, 4188-4199). In this communication we investigated the contribution of
      ligand-dependent and orphan nuclear receptors on the transcriptional regulation
      of the human apoCII gene. It was found that element CIIC in addition to ARP-1 and
      EAR-2 binds RXRalpha/T3Rbeta heterodimers strongly, whereas element CIIB binds
      hepatic nuclear factor 4 (HNF-4) exclusively. Binding is abolished by mutations
      that alter the HRE binding motifs. Transient cotransfection experiments showed
      that in the presence of T3, RXRalpha/T3Rbeta heterodimers transactivated the 
      205/+18 apoCII promoter 1.6- and 11-fold in HepG2 and COS-1 respectively. No
      transactivation was observed in the presence of 9-cis-retinoic acid.
      Transactivation requires the regulatory element CIIC, suggesting that this
      element contains a thyroid hormone response element. HNF-4 did not affect the
      apoCII promoter activity in HepG2 cells. However, mutations in the HNF-4 binding
      site on element CIIB and inhibition of HNF-4 synthesis in HepG2 cells by
      antisense HNF-4 constructs decreased the apoCII promoter activity to 25-40% of
      the control, indicating that HNF-4 is a positive regulator of the apoCII gene.
      ARP-1 repressed the -205/+18 but not the -104/+18 apoCII promoter activity in
      HepG2 cells, indicating that the repression depends on the regulatory element
      CIIC. In contrast, combination of ARP-1 and HNF-4 transactivated different apoCII
      promoter segments as well as a minimal adenovirus major late promoter driven by
      the regulatory element CIIB. Mutagenesis or deletion of elements CIIB or CIIC
      established that the observed transactivation requires DNA binding of one of the
      two factors and may result from HNF-4-ARP-1 interactions that elicit the
      transactivation functions of HNF-4. The combined data indicate that
      RXRalpha/T3Rbeta in the presence of T3 and HNF-4 can upregulate the apoCII
      promoter activity by binding to the regulatory elements CIIC and CIIB,
      respectively. In addition, ARP-1 can either have inhibitory or stimulatory
      effects on the apoCII promoter activity via different mechanisms.

PMID- 9651384
TI  - Lipid products of phosphoinositide 3-kinase and phosphatidylinositol 4',5'
      bisphosphate are both required for ADP-dependent platelet spreading.
AB  - We have shown previously that ADP released upon platelet adhesion mediated by
      alphaIIb beta3 integrin triggers accumulation of phosphatidylinositol 3',4'
      bisphosphate (PtdIns-3,4-P2) (Gironcel, D. , Racaud-Sultan, C., Payrastre, B.,
      Haricot, M., Borchert, G., Kieffer, N., Breton, M., and Chap, H. (1996) FEBS
      Lett. 389, 253-256). ADP has also been involved in platelet spreading. Therefore,
      in order to study a possible role of phosphoinositide 3-kinase in platelet
      morphological changes following adhesion, human platelets were pretreated with
      specific phosphoinositide 3-kinase inhibitors LY294002 and wortmannin. Under
      conditions where PtdIns-3, 4-P2 synthesis was totally inhibited (25 microM
      LY294002 or 100 nM wortmannin), platelets adhered to the fibrinogen matrix,
      extended pseudopodia, but did not spread. Moreover, addition of ADP to the medium
      did not reverse the inhibitory effects of phosphoinositide 3-kinase inhibitors on
      platelet spreading. Although synthetic dipalmitoyl PtdIns-3,4-P2 and dipalmitoyl
      phosphatidylinositol 3',4', 5'-trisphosphate restored only partially platelet
      spreading, phosphatidylinositol 4',5'-bisphosphate (PtdIns-4,5-P2) was able to
      trigger full spreading of wortmannin-treated adherent platelets. Following 32P
      labeling of intact platelets, the recovery of [32P]PtdIns-4,5-P2 in anti-talin
      immunoprecipitates from adherent platelets was found to be decreased upon
      treatment by wortmannin. These results suggest that the lipid products of
      phosphoinositide 3-kinase are required but not sufficient for ADP-induced
      spreading of adherent platelets and that PtdIns-4,5-P2 could be a downstream
      messenger of this signaling pathway.

PMID- 9651385
TI  - Complete exon-intron organization of the human gene for the alpha1 chain of type
      XV collagen (COL15A1) and comparison with the homologous COL18A1 gene.
AB  - The human gene for the alpha1 chain of type XV collagen (COL15A1) is about 145
      kilobases in size and contains 42 exons. The promoter is characterized by the
      lack of a TATAA motif and the presence of several Sp1 binding sites, some of
      which appeared to be functional in transfected HeLa cells. Comparison with
      Col18a1, which encodes the alpha1(XVIII) collagen chain homologous with
      alpha1(XV), indicates marked structural homology spread throughout the two genes.
      The mouse Col18a1 contains one exon more than COL15A1, due to the fact that
      COL15A1 lacks sequences corresponding to exon 3 of Col18a1, which encodes a
      cysteine-rich sequence motif. Twenty-five of the exons of the two genes are
      almost identical in size, six of them contain conserved split codons, and the
      locations of the respective exon-intron junctions are identical or almost
      identical in the two genes. The homologous exons include the closely adjacent
      first pair of exons and the exons encoding a thrombospondin-1 homology found in
      the N-terminal noncollagenous domain 1, which are followed by the most variable
      part of the two genes, covering the C-terminal half of their noncollagenous
      domain 1 and the beginning of the collagenous portion, after which most of the
      exons are homologous. The lengths of the introns are not similar in these genes,
      with two exceptions, namely the first intron, which is very short, less than 100
      base pairs, and the second intron, which is very large, about 50 kilobases, in
      both genes. It can be concluded that COL15A1 and Col18a1 are derived from a
      common ancestor.

PMID- 9651386
TI  - Differential expression of agrin in renal basement membranes as revealed by
      domain-specific antibodies.
AB  - We determined the specificity of two hamster monoclonal antibodies and a sheep
      polyclonal antiserum against heparan sulfate proteoglycan isolated from rat
      glomerular basement membrane. The antibodies were characterized by enzyme-linked
      immunosorbent assay on various basement membrane components and
      immunoprecipitation with heparan sulfate proteoglycan with or without
      heparitinase pre-treatment. These experiments showed that the antibodies
      specifically recognize approximately 150-, 105-, and 70-kDa core proteins of rat
      glomerular basement membrane heparan sulfate proteoglycan. Recently, we showed
      that agrin is a major heparan sulfate proteoglycan in the glomerular basement
      membrane (Groffen, A. J. A., Ruegg, M. A., Dijkman, H. B. P. M., Van der Velden,
      T. J., Buskens, C. A., van den Born, J., Assmann, K. J. M., Monnens, L. A. H.,
      Veerkamp, J. H., and van den Heuvel, L. P. W. J. (1998) J. Histochem. Cytochem.
      46, 19-27). Therefore, we tested whether our antibodies recognize agrin. To this
      end, we evaluated staining of Chinese hamster ovary cells transfected with
      constructs encoding full-length or the C-terminal half of rat agrin by analysis
      on a fluorescence-activated cell sorter. Both hamster monoclonals and the sheep
      antiserum clearly stained cells transfected with the construct encoding full
      length agrin, whereas wild type cells and cells transfected with the construct
      encoding the C-terminal part of agrin were not recognized. A panel of previously
      characterized monoclonals, directed against C-terminal agrin, clearly stained
      cells transfected with either of the constructs but not wild type cells. This
      indicates that both hamster monoclonals and the sheep antiserum recognize
      epitopes on the N-terminal half of agrin. By immunohistochemistry on rat renal
      tissue, we compared distribution of N-terminal agrin with that of C-terminal
      agrin. The monoclonal antibodies against C-terminal agrin stained almost
      exclusively the glomerular basement membrane, whereas the anti-N-terminal agrin
      antibodies recognized all renal basement membranes, including tubular basement
      membranes. Based on these results, we hypothesize that full-length agrin is
      predominantly expressed in the glomerular basement membrane, whereas in most
      other renal basement membranes a truncated isoform of agrin is predominantly
      found that misses (part of) the C terminus, which might be due to alternative
      splicing and/or posttranslational processing. The possible significance of this
      finding is discussed.

PMID- 9651387
TI  - Characterization of recombinant CD45 cytoplasmic domain proteins. Evidence for
      intramolecular and intermolecular interactions.
AB  - CD45 is a transmembrane two-domain tyrosine phosphatase required for efficient
      signal transduction initiated by lymphocyte antigen receptors. As with most
      transmembrane two-domain phosphatases, the role of the second phosphatase domain
      is unclear. In this study, recombinant CD45 cytoplasmic domain proteins purified
      from bacteria were used to evaluate the function of the individual phosphatase
      domains. A recombinant protein expressing the membrane-proximal region, first
      phosphatase domain, and spacer region of CD45 (rD1) was catalytically active and
      found to exist primarily as a dimer. In contrast to this, a recombinant protein
      expressing the spacer region, the second phosphatase domain and the carboxy tail
      of CD45 (rD2) existed as a monomer and had no catalytic activity against any of
      the substrates tested. Comparison of rD1 with the recombinant protein expressing
      the entire cytoplasmic domain of CD45 (rD1/D2) indicated that rD1/D2 was 2-3-fold
      more catalytically active, was more thermostable, and existed primarily as a
      monomer. Limited trypsin digestion of rD1/D2 provided evidence for a noncovalent
      association between an N-terminal 27-kDa fragment and a C-terminal 53-kDa
      fragment, suggesting an intramolecular interaction. Furthermore, rD1 was found to
      specifically associate with rD2 in an in vitro binding assay. Taken together,
      these data provide evidence for an intramolecular interaction occurring in the
      cytoplasmic domain of CD45. In the absence of the C-terminal region containing
      the second phosphatase domain, intermolecular interactions occur, resulting in
      dimer formation.

PMID- 9651388
TI  - Increased mature interleukin-1beta (IL-1beta) secretion from THP-1 cells induced
      by nigericin is a result of activation of p45 IL-1beta-converting enzyme
      processing.
AB  - Perregaux and Gabel (Perregaux, D., and Gabel, C. A. (1994) J. Biol. Chem. 269,
      15195-15203) reported that potassium depletion of lipopolysaccharide-stimulated
      mouse macrophages induced by the potassium ionophore, nigericin, leads to the
      rapid release of mature interleukin-1beta (IL-1beta). We have now shown a similar
      phenomenon in lipopolysaccharide-stimulated human monocytic leukemia THP-1 cells.
      Rapid secretion of mature, 17-kDa IL-1beta occurred, in the presence of nigericin
      (4-16 microM). No effects on the release of tumor necrosis factor-alpha, IL-6, or
      proIL-1beta were seen. Addition of the irreversible interleukin-1beta-converting
      enzyme (ICE) inhibitor, Z-Val-Ala-Asp-dichlorobenzoate, or a radicicol analog,
      inhibited nigericin-induced mature IL-1beta release and activation of p45 ICE
      precursor. The radicicol analog itself did not inhibit ICE, but markedly, and
      very rapidly depleted intracellular levels of 31-kDa proIL-1beta. By contrast,
      dexamethasone, cycloheximide, and the Na+/H+ antiporter inhibitor, 5-(N-ethyl-N
      isopropyl)amiloride, had no effect on nigericin-induced release of IL-1beta. We
      have therefore shown conclusively, for the first time, that nigericin-induced
      release of IL-1beta is dependent upon activation of p45 ICE processing. So far,
      the mechanism by which reduced intracellular potassium ion concentration triggers
      p45 ICE processing is not known, but further investigation in this area could
      lead to the discovery of novel molecular targets whereby control of IL-1beta
      production might be effected.

PMID- 9651389
TI  - HIV-1 Tat induces neuronal death via tumor necrosis factor-alpha and activation
      of non-N-methyl-D-aspartate receptors by a NFkappaB-independent mechanism.
AB  - Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous
      system may result in neuronal apoptosis in vulnerable brain regions, including
      cerebral cortex and basal ganglia. The mechanisms for neuronal loss are likely to
      be multifactorial and indirect, since HIV-1 productively infects brain-resident
      macrophages and microglia but does not cause cytolytic infection of neurons in
      the central nervous system. HIV-1 infection of macrophages and microglia leads to
      production and release of diffusible factors that result in neuronal cell death,
      including the HIV-1 regulatory protein Tat. We demonstrate in this report that
      recombinant Tat1-86 and Tat peptides containing the basic region induce neuronal
      apoptosis in approximately 50% of vulnerable neurons in both rat and human
      neuronal cultures, and this apoptotic cell death is mediated by release of the
      pro-inflammatory cytokine tumor necrosis factor alpha, and by activation of
      glutamate receptors of the non-N-methyl-D-aspartate subtype. Finally, we show
      that Tat-induced apoptosis of human neuronal cell cultures occurs in the absence
      of activation of the transcription factor NFkappaB. These findings further define
      cellular pathways activated by Tat, that dysregulate production of tumor necrosis
      factor alpha, and lead to activation of glutamate receptors and neuronal death
      during HIV-1 infection of the central nervous system.

PMID- 9651390
TI  - The N-terminal region of yeast TFIIB contains two adjacent functional domains
      involved in stable RNA polymerase II binding and transcription start site
      selection.
AB  - The general transcription factor IIB (TFIIB) is required for accurate and
      efficient transcription of protein-coding genes by RNA polymerase II (RNAPII). To
      define functional domains in the highly conserved N-terminal region of TFIIB, we
      have analyzed 14 site-directed substitution mutants of yeast TFIIB for their
      ability to support cell viability, transcription in vitro, accurate start site
      selection in vitro and in vivo, and to form stable complexes with purified RNAPII
      in vitro. Mutations impairing the formation of stable TFIIB.RNAPII complexes
      mapped to the zinc ribbon fold, whereas mutations conferring downstream shifts in
      transcription start site selection were identified at multiple positions within a
      highly conserved homology block adjacent and C-terminal to the zinc ribbon. These
      results demonstrate that the N-terminal region of yeast TFIIB contains two
      separable and adjacent functional domains involved in stable RNAPII binding and
      transcription start site selection, suggesting that downstream shifts in
      transcription start site selection do not result from impairment of stable
      TFIIB.RNAPII binding. We discuss models for yeast start site selection in which
      TFIIB may affect the ability of preinitiation complexes to interact with
      downstream DNA or to affect start site recognition by a scanning polymerase.

PMID- 9651391
TI  - CBP is required for sterol-regulated and sterol regulatory element-binding
      protein-regulated transcription.
AB  - Cells were transfected with luciferase reporter genes, under the control of
      promoters derived from either the farnesyl diphosphate (FPP) synthase, 3-hydroxy
      3-methylglutaryl coenzyme A (HMG-CoA) synthase, HMG-CoA reductase, or low density
      lipoprotein receptor genes. The increase in luciferase activity that occurred
      when cells were either incubated in sterol-depleted medium or cotransfected with
      a cDNA encoding sterol regulatory element-binding protein (SREBP)-1a was
      prevented by coexpression of wild-type E1A or a Gal4-CBP (1-451) fusion protein.
      The inhibitory effect of E1A was overcome by coexpression of CBP. The increase in
      reporter gene activity noted above was not affected when the cells were
      cotransfected with cDNAs that encoded either a mutant E1A that is unable to
      interact with the transcriptional activator CBP or Gal4-CBP fusion proteins
      encoding separate fragments of CBP, which span the remainder of the CBP molecule.
      A preformed SREBP-1a:[32P]DNA complex bound specifically to membrane-immobilized
      GST-CBP fusion proteins that contained amino-terminal portions of CBP. In order
      to investigate the role of CBP in the regulation of endogenous genes, we isolated
      stable transformants that express Gal4-CBP(1-451) in response to added
      doxycycline. Induction of endogenous FPP synthase and HMG-CoA synthase mRNAs, in
      response to cellular cholesterol depletion, was prevented when cells expressed
      Gal4-CBP(1-451). We conclude that when cells are incubated in the absence of
      sterols, the transcriptional activation of the HMG-CoA synthase, HMG-CoA
      reductase, FPP synthase, and low density lipoprotein receptor genes is dependent
      on a specific interaction between SREBP, which is bound to the promoter DNA, and
      the amino-terminal domain (amino acids 1-451) of CBP.

PMID- 9651392
TI  - Nitroxides tempol and tempo induce divergent signal transduction pathways in MDA
      MB 231 breast cancer cells.
AB  - Tempol and tempo are stable free radical nitroxides that possess antioxidant
      properties. In this study, we examined the effects of these compounds on
      components of the mitogen-activated protein kinase signal transduction cascade.
      Tempo treatment (15 min) of MDA-MB 231 human breast cancer cells resulted in
      significant levels of tyrosine phosphorylation of several as yet unidentified
      proteins compared with equimolar concentration of tempol (10 mM). Both compounds
      caused tyrosine phosphorylation and activation of Raf-1 protein kinase (30 min, 2
      3-fold). Interestingly, however, only tempol caused increased extracellular
      signal-regulated kinase 1 activity (2 h, approximately 3-fold). On the other
      hand, tempo, but not tempol, potently activated stress-activated protein kinase
      (2 h, >3-fold). Consistent with these data, tempol was found to be noncytotoxic,
      whereas tempo induced apoptotic cell death (2 h, >50%). Tempo treatment also
      resulted in significant elevation of ceramide levels at 30 min (54% over control)
      and 1 h (71% over control) posttreatment, preceding stress-activated protein
      kinase activation and apoptosis. These data suggest that in the absence of an
      environmental oxidative stress, tempol and tempo elicit distinct cellular
      signaling pathways. The recognition of the molecular mechanisms of nitroxide
      action may have important implications for biological effectiveness of these
      compounds.

PMID- 9651393
TI  - Topoisomerase IV catalysis and the mechanism of quinolone action.
AB  - Topoisomerase IV is a bacterial type II topoisomerase that is essential for
      proper chromosome segregation and is a target for quinolone-based antimicrobial
      agents. Despite the importance of this enzyme to the survival of prokaryotic
      cells and to the treatment of bacterial infections, relatively little is known
      about the details of its catalytic mechanism or the basis by which quinolones
      alter its enzymatic functions. Therefore, a series of experiments that analyzed
      individual steps of the topoisomerase IV catalytic cycle were undertaken to
      address these critical mechanistic issues. The following conclusions were drawn.
      First, equilibrium levels of DNA cleavage mediated by the bacterial enzyme were
      considerably (>10-fold) higher than those observed with its eukaryotic
      counterparts. To a large extent, this reflected decreased rates of DNA
      religation. Second, the preference of topoisomerase IV for catalyzing DNA
      decatenation over relaxation reflects increased rates of strand passage and
      enzyme recycling rather than a heightened recognition of intermolecular DNA
      helices. Third, quinolones stimulate topoisomerase IV-mediated DNA cleavage both
      by increasing rates of DNA scission and by inhibiting religation of cleaved DNA.
      Finally, quinolones inhibit the overall catalytic activity of topoisomerase IV
      primarily by interfering with enzyme-ATP interactions.

PMID- 9651394
TI  - Functional characterization of a series of mutant G protein alphaq subunits
      displaying promiscuous receptor coupling properties.
AB  - The N termini of two G protein alpha subunits, alphaq and alpha11, differ from
      those of other alpha subunits in that they display a unique, highly conserved six
      amino acid extension (MTLESI(M)). We recently showed that an alphaq deletion
      mutant lacking these six amino acids (in contrast to wild type alphaq) was able
      to couple to several different Gs- and Gi/o-coupled receptors, apparently due to
      promiscuous receptor/G protein coupling (Kostenis, E., Degtyarev, M. Y., Conklin,
      B. R., and Wess, J. (1997) J. Biol. Chem. 272, 19107-19110). To study which
      specific amino acids within the N-terminal segment of alphaq/11 are critical for
      constraining the receptor coupling selectivity of these subunits, this region of
      alphaq was subjected to systematic deletion and alanine scanning mutagenesis. All
      mutant alphaq constructs (or wild type alphaq as a control) were coexpressed (in
      COS-7 cells) with the m2 muscarinic or the D2 dopamine receptors, two
      prototypical Gi/o-coupled receptors, and ligand-induced increases in inositol
      phosphate production were determined as a measure of G protein activation.
      Surprisingly, all 14 mutant G proteins studied (but not wild type alphaq) gained
      the ability to productively interact with the two Gi/o-linked receptors. Similar
      results were obtained when we examined the ability of selected mutant alphaq
      subunits to couple to the Gs-coupled beta2-adrenergic receptor. Additional
      experiments indicated that the functional promiscuity displayed by all
      investigated mutant alphaq constructs was not due to overexpression (as compared
      with wild type alphaq), lack of palmitoylation, or initiation of translation at a
      downstream ATG codon (codon seven). These data are consistent with the notion
      that the six-amino acid extension characteristic for alphaq/11 subunits forms a
      tightly folded protein subdomain that is critical for regulating the receptor
      coupling selectivity of these subunits.

PMID- 9651395
TI  - Cloning and characterization of a novel matrix metalloproteinase (MMP), CMMP,
      from chicken embryo fibroblasts. CMMP, Xenopus XMMP, and human MMP19 have a
      conserved unique cysteine in the catalytic domain.
AB  - We cloned a novel matrix metalloproteinase (MMP) called CMMP from cultured
      primary chicken embryo fibroblasts. The cDNA-derived CMMP sequence contains 472
      amino acids including a putative 19-residue signal peptide and a unique cysteine
      in the catalytic domain, an insertion in a sequence motif that binds the
      structural (noncatalytic) zinc of MMPs. Strikingly, a homologously inserted
      cysteine is also found in Xenopus XMMP and human MMP19, two recently cloned novel
      members of the MMP family. Phylogenetic analysis suggest that XMMP and MMP19
      represent founding members of the MMP family, whereas CMMP is related to
      collagenase MMPs. Bacterially produced recombinant CMMP (without the amino
      terminal inhibition domain), which was autoproteolyzed at the carboxyl-terminal
      domain, digested casein and gelatin. As shown by Northern blotting, CMMP mRNA of
      1.8 kilobase pairs was constitutively expressed in cultured primary chicken
      embryo fibroblasts and up-regulated by tumor necrosis factor-alpha and the
      phorbol ester 12-O-tetradecanoylphorbol-13-acetate, but it was not regulated by
      interleukin-1, basic fibroblast growth factor, or retinoic acid. CMMP mRNA of 1.8
      kb was also detected in the head and body of 8-day-old chicken embryos and
      dramatically up-regulated in 9-day-old embryos.

PMID- 9651396
TI  - Crucial role of N terminus in function of cardiac L-type Ca2+ channel and its
      modulation by protein kinase C.
AB  - The role of the cytosolic N terminus of the main subunit (alpha1C) of cardiac L
      type voltage-dependent Ca2+ channel was studied in Xenopus oocyte expression
      system. Deletion of the initial 46 or 139 amino acids (a.a.) of rabbit heart
      alpha1C caused a 5-10-fold increase in the whole cell Ca2+ channel current
      carried by Ba2+ (IBa), as reported previously (Wei, X., Neely, A., Olcese, R.,
      Lang, W., Stefani, E., and Birnbaumer, L. (1996) Recept. Channels 4, 205-215).
      The plasma membrane content of alpha1C protein, measured immunochemically, was
      not altered by the 46-a.a. deletion. Patch clamp recordings in the presence of a
      dihydropyridine agonist showed that this deletion causes a approximately 10-fold
      increase in single channel open probability without changing channel density.
      Thus, the initial segment of the N terminus affects channel gating rather than
      expression. The increase in IBa caused by coexpression of the auxiliary beta2A
      subunit was substantially stronger in channels with full-length alpha1C than in
      46- or 139-a.a. truncated mutants, suggesting an interaction between beta2A and N
      terminus. However, only the I-II domain linker of alpha1C, but not to N or C
      termini, bound beta2A in vitro. The well documented increase of IBa caused by
      activation of protein kinase C (PKC) was fully eliminated by the 46-a.a.
      deletion. Thus, the N terminus of alpha1C plays a crucial role in channel gating
      and PKC modulation. We propose that PKC and beta subunit enhance the activity of
      the channel in part by relieving an inhibitory control exerted by the N terminus.
      Since PKC up-regulation of L-type Ca2+ channels has been reported in many
      species, we predict that isoforms of alpha1C subunits containing the initial N
      terminal 46 a.a. similar to those of the rabbit heart alpha1C are widespread in
      cardiac and smooth muscle cells.

PMID- 9651397
TI  - cDNA cloning, tissue distribution, and substrate characteristics of a cis
      Retinol/3alpha-hydroxysterol short-chain dehydrogenase isozyme.
AB  - We report here a mouse cDNA that encodes a 316-amino acid short-chain
      dehydrogenase that prefers NAD+ as its cofactor and recognizes as substrates
      androgens and retinols, i.e. has steroid 3alpha- and 17beta-dehydrogenase and
      cis/trans-retinol catalytic activities. This cis-retinol/androgen dehydrogenase
      type 2 (CRAD2) shares close amino acid similarity with mouse retinol
      dehydrogenase isozyme types 1 and 2 and CRAD1 (86, 84, and 87%, respectively).
      CRAD2 exhibits cooperative kinetics with 3alpha-adiol (3alpha-hydroxysteroid
      dehydrogenase activity) and testosterone (17beta-hydroxysteroid dehydrogenase
      activity), but Michaelis-Menten kinetics with androsterone (3alpha-hydroxysteroid
      dehydrogenase activity), 11-cis-retinol, all-trans-retinol, and 9-cis-retinol,
      with V/K0.5 values of 1.6, 0.2, 0.1, 0.04, 0.005, and not saturated,
      respectively. Carbenoxolone (IC50 = 2 microM) and 4-methylpyrazole (IC50 = 5 mM)
      inhibited CRAD2, but neither ethanol nor phosphatidylcholine had marked effects
      on its activity. Liver expressed CRAD2 mRNA intensely, with expression in lung,
      eye, kidney, and brain (2.9, 2, 1.6, and 0.6% of liver mRNA, respectively). CRAD2
      represents the fifth isozyme in a group of short-chain dehydrogenase/reductase
      isozymes (retinol dehydrogenases 1-3 and CRAD1), closely related in primary amino
      acid sequence (approximately 85%), that are expressed in different quantities in
      various tissues, have different substrate specificities, and may serve different
      physiological functions. CRAD2 may alter the amounts of active and inactive
      androgens and/or convert retinols into retinals. These data expand insight into
      the multifunctional nature of short-chain dehydrogenases/reductases and into the
      enzymology of steroid and retinoid metabolism.

PMID- 9651399
TI  - A potent cell death activity associated with transient high level expression of
      BCL-2.
AB  - The BCL-2 proto-oncogene contains unusually long untranslated 5' and 3'
      sequences. Deletion of the sequences flanking the BCL-2 open reading frame
      dramatically increases the level of protein expression. Transient high level BCL
      2 protein expression mediated by plasmid transfection or by infection with
      recombinant adenovirus results in potent apoptosis of several cell lines.
      Detailed mutational (deletion and add-back) analysis reveals that both 5'- and 3'
      flanking sequences contribute to the negative modulation of protein expression
      from the BCL-2 open reading frame. It appears that these sequences exert the
      negative regulatory effect in an orientation-dependent manner. Analysis of BCL-2
      RNA levels indicate that elevated levels of mRNA may be the primary cause of
      elevated levels of protein expression. Apoptosis induced by adenovirus vectors
      expressing elevated levels of BCL-2 can be readily inhibited by the caspase
      inhibitor z-VAD-fmk, suggesting that high levels of BCL-2 expression induce
      apoptosis via the caspase cascade. Mutational analysis of BCL-2 indicates that
      its pro-apoptotic activity is separable from its anti-apoptosis activity. Our
      results raise the possibility that oncogenic conversion of BCL-2 may require
      somatic mutations in the pro-apoptotic activity, in addition to other activating
      mutations that result in enhanced expression. Consistent with this hypothesis, a
      somatic mutation of BCL-2 observed in multiple human tumors results in reduced
      apoptosis activity.

PMID- 9651400
TI  - Biochemical coupling between the DrrA and DrrB proteins of the doxorubicin efflux
      pump of Streptomyces peucetius.
AB  - The drrAB operon of Streptomyces peucetius encodes for resistance to the
      antibiotics doxorubicin and daunorubicin. Subcloning of the drrAB genes in
      Escherichia coli has previously been shown to result in expression of DrrA and
      DrrB proteins and resistance to doxorubicin in a sensitive strain of E. coli.
      DrrA, a peripheral membrane protein, binds ATP in a UV-catalyzed reaction in a
      doxorubicin-dependent manner; DrrB, a hydrophobic protein, is localized to the
      inner membrane of E. coli (Kaur, P. (1997) J. Bacteriol. 179, 569-575). The
      present study provides evidence that DrrB, the membrane component of the complex,
      is stably maintained in the cell only if DrrA is present. Furthermore, it was
      found that the catalytic component DrrA is in an active conformation only when it
      is in a complex with DrrB. In a subclone containing the drrB gene by itself, no
      DrrB protein could be detected, although a translational fusion of the first 15
      amino acids of DrrB to beta-galactosidase indicated that DrrB is translated in
      the absence of DrrA. Upon co-transformation with a plasmid containing the drrA
      gene in trans, DrrB could again be detected in these cells. UV cross-linking
      studies with [alpha-32P]ATP showed that only the membrane-bound form of DrrA in
      cells containing both DrrA and DrrB was in a conformation competent to bind ATP.
      Chemical cross-linking studies also provided direct evidence for interaction
      between the two proteins. Based on these analyses, a model for interaction
      between DrrA and DrrB proteins is presented.

PMID- 9651398
TI  - The gut-enriched Kruppel-like factor suppresses the activity of the CYP1A1
      promoter in an Sp1-dependent fashion.
AB  - The gut-enriched Kruppel-like factor (GKLF) is a newly identified zinc finger
      containing transcription factor. Recent studies indicate that GKLF binds to a
      core DNA sequence of 5'-(G/A)(G/A)GG(C/T)G(C/T)-3', which is found in an
      endogenous cis element, the basic transcription element (BTE) of the cytochrome P
      450IA1 (CYP1A1) promoter. The present study characterizes the ability of GKLF to
      regulate CYP1A1 expression. By electrophoretic mobility gel shift assay (EMSA)
      and methylation interference assay, GKLF was found to bind BTE in a manner
      similar to several other transcription factors known to interact with BTE
      including Sp1 and BTEB. Cotransfection studies in Chinese hamster ovary cells
      showed that GKLF inhibited the CYP1A1 promoter in a dose- and BTE-dependent
      manner. The same experiments also revealed that BTE was responsible for a
      significant portion of the CYP1A1 promoter activity. EMSA of nuclear extracts
      from Chinese hamster ovary cells showed that Sp1 and Sp3 were two major proteins
      that interacted with BTE. Additional cotransfection studies showed that GKLF
      inhibited Sp1-mediated activation of the CYP1A1 promoter. In contrast, GKLF
      enhanced Sp3-dependent suppression of the same promoter. Moreover, the ability of
      GKLF to inhibit Sp1-dependent transactivation was in part due to physical
      interaction of the two proteins. These findings indicate that GKLF is a negative
      regulator of the CYP1A1 promoter in a BTE-dependent fashion and that this
      inhibitory effect is in part mediated by physical interaction with Sp1.

PMID- 9651401
TI  - Identification of the hepatic protein targets of reactive metabolites of
      acetaminophen in vivo in mice using two-dimensional gel electrophoresis and mass
      spectrometry.
AB  - Liver toxicity following an overdose of acetaminophen is frequently considered a
      model for drug-induced hepatotoxicity. Extensive studies over many years have
      established that such toxicity is well correlated with liver protein arylation by
      acetaminophen metabolites. Identification of protein targets for covalent
      modifications is a challenging but necessary step in understanding how covalent
      binding could lead to liver toxicity. Previous approaches suffered from technical
      limitations, and thus over the last 10 years heroic efforts were required to
      determine the identity of only a few target proteins. We present a new mass
      spectrometry-based strategy for identification of all target proteins that now
      provides a comprehensive survey of the suite of liver proteins modified. After
      administration of radiolabeled acetaminophen to mice, the proteins in the liver
      tissue lysate were separated by two-dimensional polyacrylamide gel
      electrophoresis. In-gel digestion of the radiolabeled gel spots gave a set of
      tryptic peptides, which were analyzed by matrix-assisted laser desorption
      ionization mass spectrometry. Interrogation of data bases based on experimentally
      determined molecular weights of peptides and product ion tags from postsource
      decay mass spectra was employed for the determination of the identities of
      modified liver proteins. Using this method, more than 20 new drug-labeled
      proteins have been identified.

PMID- 9651402
TI  - Involvement of retinoic acid/retinoid receptors in the regulation of murine
      alphaB-crystallin/small heat shock protein gene expression in the lens.
AB  - Crystallins are a diverse group of abundant soluble proteins that are responsible
      for the refractive properties of the transparent eye lens. We showed previously
      that Pax-6 can activate the alphaB-crystallin/small heat shock protein promoter
      via the lens-specific regulatory regions LSR1 (-147/-118) and LSR2 (-78/-46).
      Here we demonstrate that retinoic acid can induce the accumulation of alphaB
      crystallin in N/N1003A lens cells and that retinoic acid receptor heterodimers
      (retinoic acid receptor/retinoid X receptor; RAR/RXR) can transactivate LSR1 and
      LSR2 in cotransfection experiments. DNase I footprinting experiments demonstrated
      that purified RAR/RXR heterodimers will occupy sequences resembling retinoic acid
      response elements within LSR1 and LSR2. Electrophoretic mobility shift assays
      using antibodies indicated that LSR1 and LSR2 can interact with endogenous
      RAR/RXR complexes in extracts of cultured lens cells. Pax-6 and RAR/RXR together
      had an additive effect on the activation of alphaB-promoter in the transfected
      lens cells. Thus, the alphaB-crystallin gene is activated by Pax-6 and retinoic
      acid receptors, making these transcription factors examples of proteins that have
      critical roles in early development as well as in the expression of proteins
      characterizing terminal differentiation.

PMID- 9651403
TI  - Structure-function relationships in OxlT, the oxalate/formate transporter of
      Oxalobacter formigenes. Topological features of transmembrane helix 11 as
      visualized by site-directed fluorescent labeling.
AB  - Analysis of hydropathy suggests that in OxlT, the oxalate/formate antiporter of
      Oxalobacter formigenes, lysine 355 is within transmembrane helix no. 11. To test
      this idea, we used single-cysteine, histidine-tagged OxlT variants to study the
      organization of a 30-residue segment (residues 344-373) containing this region.
      Topology was examined by probing the A345C and A370C proteins with Oregon Green
      maleimide carboxylic acid, an impermeant and fluorescent thiol-reactive agent.
      Examination of purified protein showed that only A370C was fluorescent after
      treating intact cells with the probe, while both proteins were modified in tests
      with isolated membrane ghosts. In addition, labeling of A370C, but not A345C, was
      blocked when external cysteines were protected with the impermeant and
      nonfluorescent agent, methanethiosulfonate ethyltrimethylammonium. These findings
      confirm that A345 faces the cytoplasm, while A370C faces the periplasm. A similar
      study focused on 13 single-cysteine variants positioned throughout the target
      segment. That work revealed a striking discontinuity in reactivity toward Oregon
      Green maleimide; cysteines within a 10-residue central core (residues 351-360)
      were not labeled when membranes were probed, but were readily modified after
      protein denaturation. We suggest this core resides within the lipid bilayer,
      unavailable to an impermeant reporter. Since this region includes position 355,
      we also suggest that lysine 355 lies within the OxlT hydrophobic sector, where it
      may facilitate the binding and translocation of the anionic substrates, oxalate
      and formate.

PMID- 9651404
TI  - Identification of an insulin-responsive, slow endocytic recycling mechanism in
      Chinese hamster ovary cells.
AB  - In adipocytes, the insulin-regulated aminopeptidase (IRAP) is trafficked through
      the same insulin-regulated recycling pathway as the GLUT4 glucose transporter. We
      find that a chimera, containing the cytoplasmic domain of IRAP fused to
      transmembrane and extracellular domains of the transferrin receptor, is slowly
      recycled and rapidly internalized in Chinese hamster ovary cells. Morphological
      studies indicate that the chimera is slowly trafficked through the general
      endosomal recycling compartment rather than being sorted to a specialized
      recycling pathway. A chimera in which a di-leucine sequence within the
      cytoplasmic domain of IRAP has been mutated to alanines is rapidly internalized
      and rapidly recycled, indicating that this di-leucine is required for the slow
      recycling but not for the rapid internalization. Insulin stimulates a 2-3-fold
      increase in the recycling of the chimera and only a 1.2-fold increase in the
      recycling of the transferrin receptor. The effect of insulin on the recycling of
      the chimera is blocked by wortmannin, a phosphatidylinositol 3'-kinase inhibitor.
      GTPgammaS (guanosine 5'-3-O-(thio)triphosphate) increases the recycling of the
      chimera by 50% but has no effect on the recycling of the transferrin receptor. In
      these studies, we have identified in Chinese hamster ovary cells a novel, slow
      endocytic recycling mechanism that is regulated by insulin.

PMID- 9651405
TI  - Zinc supplementation reduces the incidence of acute lower respiratory infections
      in infants and preschool children: a double-blind, controlled trial.
AB  - BACKGROUND: Increased acute lower respiratory infection incidence, severity, and
      mortality are associated with malnutrition, and reduced immunological competence
      may be a mechanism for this association. Because zinc deficiency results in
      impaired immunocompetence and zinc supplementation improves immune status, we
      hypothesized that zinc deficiency is associated with increased incidence and
      severity of acute lower respiratory infection. METHODS: We evaluated the effect
      of daily supplementation with 10 mg of elemental zinc on the incidence and
      prevalence of acute lower respiratory infection in a double-blind, randomized,
      controlled trial in 609 children (zinc, n = 298; control, n = 311) 6 to 35 months
      of age. Supplementation and morbidity surveillance were done for 6 months.
      RESULTS: After 120 days of supplementation, the percentage of children with
      plasma zinc concentrations <60 microg/dL decreased from 35.6% to 11.6% in the
      zinc group, whereas in the control group it increased from 36.8% to 43.6%. Zinc
      supplemented children had 0.19 acute lower respiratory infection
      episodes/child/year compared with 0.35 episodes/child/year in the control
      children. After correction for correlation of data using generalized estimating
      equation regression methods, there was a reduction of 45% (95% confidence
      interval, 10% to 67%) in the incidence of acute lower respiratory infections in
      zinc-supplemented children. CONCLUSIONS: A dietary zinc supplement resulted in a
      significant reduction in respiratory morbidity in preschool children. These
      findings suggest that interventions to improve zinc intake will improve the
      health and survival of children in developing countries.

PMID- 9651406
TI  - A randomized, placebo-controlled trial of granulocyte colony-stimulating factor
      administration to newborn infants with neutropenia and clinical signs of early
      onset sepsis.
AB  - OBJECTIVE: To determine whether recombinant human granulocyte colony-stimulating
      factor (G-CSF) administration: 1) accelerates production of neutrophils; 2)
      increases bone marrow stored and precursor neutrophils; and 3) is safe in newborn
      infants with neutropenia and clinical signs of early-onset sepsis. STUDY DESIGN:
      We randomized 20 infants with neutropenia and clinical signs of early-onset
      sepsis in the first 3 days of life to receive G-CSF (10 microg/kg/d) or placebo
      for 3 days. Entry criteria included neutropenia as defined by Manroe criteria, an
      elevated immature to total neutrophil ratio [(I/T) >/=0.25], and a requirement
      for ventilatory support. Cultures were obtained and antibiotics initiated on all
      study infants. Circulating absolute neutrophil count (ANC), I/T ratio, bone
      marrow neutrophil storage pool (NSP) and neutrophil proliferative pool (NPP), and
      plasma G-CSF concentrations were evaluated. Also, severity of illness as
      determined using the Score for Neonatal Acute Physiology (SNAP), morbidity, and
      mortality were recorded. RESULTS: Circulating ANC increased in both G-CSF and
      placebo recipients by day 1. Also, the I/T neutrophil ratio decreased in both G
      CSF and placebo recipients. There were no significant differences in the ANC or
      I/T ratio between the two groups during the study period. Similarly, bone marrow
      NSP and NPP did not differ between G-CSF and placebo recipients at study entry or
      day 2. No differences were observed in the secondary outcome measures including
      severity of illness, morbidity, and mortality. CONCLUSIONS: Administration of
      recombinant G-CSF to infants with neutropenia and clinical signs of early-onset
      sepsis did not increase circulating ANC, or bone marrow NSP and NPP compared with
      placebo. No differences were observed between G-CSF and placebo recipients in
      severity of illness, morbidity, or mortality. No adverse effects of G-CSF
      administrations were noted.

PMID- 9651407
TI  - Course of tic severity in Tourette syndrome: the first two decades.
AB  - OBJECTIVE: Prevalence studies indicate a 10-fold higher rate of Tourette syndrome
      (TS) among children compared with adults. The purpose of this investigation was
      to examine the course of tic severity during the first 2 decades of life. METHOD:
      A birth-year cohort of 42 TS patients followed at the Yale Child Study Center was
      recontacted an average of 7.3 years after their initial clinical evaluation. Data
      concerning the onset and course of tic severity until 18 years of age were
      available on 36 TS patients. A variety of statistical techniques were used to
      model aspects of the temporal patterning of tic severity. RESULTS: Mean (SD) tic
      onset at 5.6 (2. 3) years of age was followed by a progressive pattern of tic
      worsening. On average, the most severe period of tic severity occurred at 10.0
      (2.4) years of age. In eight cases (22%), the frequency and forcefulness of the
      tics reached a severe level during the worst-ever period such that functioning in
      school was impossible or in serious jeopardy. In almost every case this period
      was followed by a steady decline in tic severity. By 18 years of age nearly half
      of the cohort was virtually tic-free. The onset of puberty was not associated
      with either the timing or severity of tics. CONCLUSIONS: A majority of TS
      patients displayed a consistent time course of tic severity. This consistency can
      be accurately modeled mathematically and may reflect normal neurobiological
      processes. Determination of the model parameters that describe each patient's
      course of tic severity may be of prognostic value and assist in the
      identification of factors that differentially influence the course of tic
      severity.

PMID- 9651408
TI  - Decreasing nonurgent emergency department utilization by Medicaid children.
AB  - OBJECTIVE: To test interventions to decrease the utilization of hospital
      emergency departments (EDs) for routine, nonemergent health care among Medicaid
      recipients. METHODS: Families of a Medicaid-recipient child presenting to a
      children's hospital ED for nonurgent problems received information from either a
      health professional or a clerical employee about the importance of a primary care
      provider and assistance with making an appointment to the provider of their
      choice. The health professional continued to work with her assigned families in
      eliminating barriers to appropriate utilization of a primary care provider for up
      to 3 months after the index ED visit. A third (comparison) group received no
      intervention. Subsequent health care utilization for each enrollee was tracked
      via Ohio Medicaid claims data throughout the four subsequent 6-month periods
      after the index ED visit. RESULTS: Children in the intervention groups had 11.1%
      and 14.5% fewer nonurgent ED visits in the 6 months after the index ED visit with
      a concomitant decrease in cost for this type of care when compared with the
      comparison group during the same time period. No difference in the number of
      preventive or ill-child primary care visits was seen. There was no difference in
      health care cost or utilization in the time period 6 to 24 months after the
      intervention. CONCLUSIONS: Interventions in pediatric EDs aimed at decreasing
      subsequent ED utilization for nonurgent care can be effective, resulting in
      modest decreases in the cost of health care for a Medicaid population.

PMID- 9651409
TI  - The association between adequacy of prenatal care utilization and subsequent
      pediatric care utilization in the United States.
AB  - OBJECTIVE: To explore the association between adequacy of prenatal care
      utilization and subsequent pediatric care utilization. DESIGN: A longitudinal
      follow-up of a nationally representative sample of infants born in 1988.
      PARTICIPANTS: Nine thousand four hundred forty women who had a live birth in
      1988, and whose child was alive at the time of interview, and 8285 women from the
      original sample who were reinterviewed in 1991. MAIN OUTCOME MEASURE: There were
      four outcome measures: number of well-child visits; adequate immunization for
      diphtheria, tetanus, and pertussis; adequate immunization for polio; and
      continuity of a regular source of care, as measured by the number of sites for
      pediatric care. RESULTS: Children whose mothers had less than adequate prenatal
      care utilization had significantly fewer well-child visits, and were
      significantly less likely to have adequate immunizations, even after income,
      health insurance coverage, content of prenatal care, wantedness of child, sites
      of prenatal and pediatric care, and maternal and pregnancy risk characteristics
      were taken into account. Less than adequate prenatal care utilization was not
      associated with having more than one pediatric care site. CONCLUSIONS: Prenatal
      care utilization can be used to identify and target interventions to women who
      are at risk for not obtaining well-child care or complete immunizations for their
      children.

PMID- 9651410
TI  - Should fewer premature infants be screened for retinopathy of prematurity in the
      managed care era?
AB  - OBJECTIVE: To determine appropriate upper limits for gestational age and birth
      weight when screening infants for retinopathy of prematurity (ROP). DESIGN:
      Retrospective survey. SETTING: Tertiary neonatal intensive care nursery.
      PATIENTS: Seven hundred seven infants born July 1, 1990 to June 30, 1996 and
      screened for ROP according to the 1988 to 1996 American Academy of Pediatrics
      guidelines. OUTCOME MEASURES: Maximum stage of ROP with respect to birth weight
      and gestational age. RESULTS: No ROP more than Stage 1 was observed in infants
      with gestational ages >/=32 weeks or birth weights >/=1500 g. All cases of
      threshold and Stage 4 ROP were confined to infants with gestational ages </=30
      weeks or birth weights <1200 g. CONCLUSIONS: The latest American Academy of
      Pediatrics screening guidelines for ROP are discretionary for infants with birth
      weights >1500 g or gestational ages >28 weeks. If ROP screening is limited to
      infants with birth weights of </=1500 g, 34.2% fewer infants would require
      screening compared with the previous <1800 g recommendation, while missing no
      cases of ROP more than Stage 1. A gestational age cut-off of </=28 weeks,
      however, is less desirable, and could potentially miss several infants with more
      advanced retinopathy (including Stage 4). If ROP screening criteria were instead
      modified to include infants of gestational ages <32 weeks, the number of patients
      requiring screening could be reduced 29.1% compared with the previous
      recommendation of <35 weeks, again without missing any cases of ROP more than
      Stage 1. Use of such a screening strategy (birth weight <1500 g or gestational
      age <32 weeks) is predicted to save in excess of 1.5 million dollars annually in
      the United States, while missing no cases of ROP more than Stage 1.

PMID- 9651411
TI  - Cost-effectiveness of care for very low birth weight infants.
AB  - OBJECTIVE: Very low birth weight (VLBW)infants (those with birth weights <1500 g)
      account for only 1.2% of births but 46% of infant deaths. Large improvements in
      neonatal technology in the last 2 decades have significantly improved survival
      prospects for infants with low birth weights, but at a high cost. Due largely to
      a lack of data, the costs of medical care during the period in which infant
      mortality is measured (the first year of life), as well as the cost-effectiveness
      of that care for VLBW infants, have not been quantified. Despite this fact,
      public policies both toward providing insurance coverage for their care, as well
      as denying payment for their treatment, have either been proposed or implemented
      on cost-effectiveness grounds. PATIENTS: The study includes all VLBW single live
      births in the state of California during 1986 and 1987 that were continuously
      eligible (through traditional channels) for the state's Medicaid program. MAIN
      OUTCOME MEASURES: Treatment costs were measured for all medical care received
      during the first year of life, including all inpatient and outpatient care
      received. The cost-effectiveness of care is measured by aggregate treatment costs
      for all singleton VLBW liveborns divided by the number of first-year survivors.
      RESULTS: Average treatment costs per first-year survivor for infants <1500 g was
      $93 800 (in 1987 constant dollars). Treatment costs per survivor were twice as
      high for infants <750 g ($273 900) as for the next highest birth weight group 750
      to 999 g ($138 800) which was itself almost twice as high as for the 1000 to 1249
      g group ($75 100). The gradient in cost-effectiveness with birth weight then
      drops off to $58 000 per survivor for infants with birth weights between 1250 and
      1499 g. CONCLUSION: Public policies aimed at improving birth outcomes by
      providing insurance coverage for pregnant women and children, such as the recent
      Medicaid expansions, can potentially be very cost-effective. Although maternal
      interventions such as prenatal care are relatively inexpensive, each normal birth
      that results instead in a VLBW birth saves $59 700 in first year medical
      expenses. However, cost savings attributable to increased birth weights depend on
      where in the birth weight distribution the increase occurs as well as the size of
      the birth weight increase. For infants with birth weights >750 g, significant
      gains can accrue from even a small shift in the birth weight distribution. A
      shift of 250 g at birth saves an average of $12 000 to $16 000 in first year
      medical costs and a shift of 500 g generates $28 000 in savings. However, there
      is a threshold effect on birth weight. For infants <750 g, increases in birth
      weight may increase medical expenditures. For instance, a shift in birth weight
      to the 750 to 999 g range increases costs by $29 000.

PMID- 9651412
TI  - Cystic fibrosis newborn screening: impact on reproductive behavior and
      implications for genetic counseling.
AB  - OBJECTIVE: To evaluate the impact of newborn screening for cystic fibrosis (CF)
      on the reproductive knowledge and behavior of CF families and to determine if
      heterozygote detection with the immunoreactive trypsinogen (IRT) method in
      conjunction with DNA analysis (IRT/DNA) influences knowledge and attitudes about
      reproduction in false-positive families. METHODS: The Wisconsin CF Neonatal
      Screening Project investigated 650 340 infants from 1985 to 1994 in a
      comprehensive randomized controlled trial to study both benefits and risks of
      newborn screening and to determine if early diagnosis would improve the prognosis
      of children with CF. Assessments of reproductive knowledge, attitudes, and
      behaviors of 135 families of children diagnosed as having CF in both the early
      treatment group and control groups were made 3 months after diagnosis using a
      questionnaire which was completed by 100 families. The same questionnaire was
      administered 1 year later to evaluate retention of information. It was completed
      by 71 families. A follow-up assessment tool was also administered in 1994 and
      responses obtained from 73 families. Knowledge, attitudes, and behavior among
      false-positive families were also assessed at the time of the sweat test in 206
      families who experienced IRT screening and 109 families tested with the IRT/DNA
      method. Follow-up assessments were completed 1 year later in 106 IRT families and
      63 IRT/DNA families. RESULTS: In families with a CF child, 95% initially
      understood that there was a 1 in 4 risk in subsequent pregnancies, and there was
      good retention of this information 1 year later. At the 1994 assessment, 52% of
      families had not yet conceived more children, but 74% of these already had
      children. In the couples in whom CF was diagnosed in the first child, 70% (95%
      confidence interval = 54% to 85%) conceived more children. There were 43
      subsequent pregnancies in 31 families. Prenatal diagnosis was used by 26% of the
      families (8/31) for 21% of the pregnancies (9/43). There were 3 pregnancies with
      CF detected, all of which were carried to term. In the false-positive groups,
      >95% of families initially understood that their child definitely did not have
      CF. There was no difference between false-positive IRT and IRT/DNA groups, and
      the information was retained at 1 year. Follow-up assessment 1 year after
      negative sweat tests revealed that 7% of the IRT and 10% of the IRT/DNA families
      still thought about the results often or constantly. When asked whether the
      experience of screening affected feelings about having more children, an
      affirmative response was obtained in 4% of IRT families but in 17% of IRT/DNA
      families. One year later, more than half of the false-positive IRT/DNA families
      did not understand that they were at increased risk of having a child with CF.
      CONCLUSIONS: We conclude that CF neonatal screening does not have a significant
      impact on the reproductive behavior of most families and that prenatal diagnosis
      is not used by the majority of CF families. IRT/DNA testing experiences seem to
      affect attitudes about having more children, and some parents are confused about
      the implications of the results, even with genetic counseling. However,
      persistent concerns about the sweat test result are limited. Questions raised by
      this study confirm the need for more research regarding the process of genetic
      counseling and its impact on reproductive attitudes and behavior in the newborn
      screening setting.

PMID- 9651413
TI  - Documentation of child physical abuse: how far have we come?
AB  - OBJECTIVES: To determine the effects of increased physician training and a
      structured clinical form on physician documentation of child physical abuse.
      DESIGN: Retrospective chart review. PARTICIPANTS: Children evaluated in the
      pediatric emergency department in 1980 and 1995 who were given the diagnosis of
      physical abuse. MEASUREMENTS: The unstructured pediatric emergency department
      form and the structured child abuse reporting form were reviewed for
      documentation of 20 items including history, physical examination, diagnostic
      procedures, and disposition. Data documented in 1980 were compared with that in
      1995. RESULTS: The only significant differences between 1980 and 1995 concerning
      documentation on the unstructured pediatric emergency department form were better
      recording in the latter year of Child Protective Services involvement and case
      disposition. Half or more of the records omitted documentation of at least one of
      the following: witnesses to injury, past injuries, description of size and/or
      color of injuries, illustration, and a genital exam. None of the records
      contained a developmental history. Significantly fewer skeletal surveys were
      obtained in 1995, although notation of the results was similar to 1980. For both
      years, the structured child abuse reporting form improved documentation of only
      two items: time of arrival to the pediatric emergency department and
      illustrations of injuries. CONCLUSIONS: Little improvement in physician
      documentation of child physical abuse was noted between 1980 and 1995 despite
      increased efforts to educate housestaff in the evaluation of child abuse during
      this time period. Although a structured form prompted physicians to document
      dates and times and to illustrate physical injuries on the diagram provided, it
      did not significantly improve documentation of other items.

PMID- 9651414
TI  - Pharmacologic and psychologic interventions for procedural pain.
AB  - OBJECTIVE: This study evaluated a combined pharmacologic and psychologic
      intervention (combined intervention, CI) relative to a pharmacologic-only (PO)
      intervention in reducing child distress during invasive procedures in childhood
      leukemia. Predictors of child distress included age, group (CI, PO), and
      procedural variables (medications and doses, technical difficulty, number of
      needles required). METHODOLOGY: This was a randomized, controlled prospective
      study that compared the PO (n = 45) and CI arms (n = 47), at 1, 6, and >12 months
      after diagnosis. A cross-sectional control group consisted of parents of 70
      patients in first remission before the prospective study. Parent questionnaires,
      staff and parent ratings, and data on medications administered, technical
      difficulty of the procedure, and needle insertions were obtained for each
      procedure. This article reports on the final data point for the project (>12
      months). RESULTS: Mothers and nurses reported lower levels of child distress in
      the CI than the PO group. The CI and PO groups showed lower levels of child and
      parent distress than the cross-sectional control group. Distress decreased
      throughout the time, and child age was inversely related to distress (younger
      children had more distress) regardless of group. Child distress was associated
      with staff perceptions of the technical difficulty of the procedure and with
      child age, but not with medications administered. CONCLUSIONS: The data showed
      that pharmacologic and psychologic interventions for procedural distress were
      effective in reducing child and parent distress and support integration of the
      two approaches. Younger children experienced more distress and warranted
      additional consideration. Staff perceptions of the technical difficulty of
      procedures were complex and potentially helpful in designing intervention
      protocols.

PMID- 9651416
TI  - A retrospective review of pediatric patients with epididymitis, testicular
      torsion, and torsion of testicular appendages.
AB  - STUDY OBJECTIVE: To compare historical features, physical examination findings,
      and testicular color Doppler ultrasound in pediatric patients with epididymitis,
      testicular torsion, and torsion of appendix testis. METHODS: A retrospective
      review of patients with the diagnosis of epididymitis, testicular torsion, or
      torsion of appendix testis. RESULTS: Ninety patients were included in the study
      (64 with epididymitis, 13 with testicular torsion, and 13 with torsion of
      appendix testis). Historical features did not differ among groups except for
      duration of symptoms. Of 13 patients with testicular torsion all had a tender
      testicle and an absent cremasteric reflex. When compared with the testicular
      torsion group, fewer patients with epididymitis had a tender testicle (69%) or an
      absent cremasteric reflex (14%). 62 (97%) patients with epididymitis had a tender
      epididymis and 43 (67%) had scrotal erythema/edema. By comparison, 3 (23%) and 5
      (38%) patients with testicular torsion had a tender epididymis or scrotal
      erythema/edema, respectively. Doppler ultrasound showed decreased or absent blood
      flow in 8 patients, 7 of whom were diagnosed with testicular torsion. Ten out of
      13 patients with testicular torsion had a salvageable testicle at the time of
      surgery. CONCLUSION: The physical examination is helpful in distinguishing among
      epididymitis, testicular torsion, and torsion of appendix testis. Patients
      presenting with a tender testicle and an absent cremasteric reflex were more
      likely to have a testicular torsion rather than epididymitis or torsion of
      appendix testis. An absent cremasteric reflex was the most sensitive physical
      finding for diagnosing testicular torsion. Color Doppler ultrasound is a useful
      adjunct in the evaluation of the acute scrotum when physical findings are
      equivocal.

PMID- 9651415
TI  - Occult bacteremia with group B streptococci in an outpatient setting.
AB  - OBJECTIVES: We undertook this study to determine the relative frequency of occult
      bacteremia with group B streptococci (GBS) and to define the clinical features of
      infants with occult bacteremia attributable to GBS at the time of initial
      clinical contact. DESIGN: The logs of the microbiology laboratory were reviewed
      for blood and cerebrospinal fluid isolates of GBS from 1982 to 1996. Records of
      patients identified with GBS were abstracted. Patients were classified as having
      occult bacteremia if GBS were isolated from their blood and they seemed nontoxic
      and had no apparent clinical or laboratory evidence of focal infection. All other
      patients were diagnosed with sepsis, meningitis, or nonmeningeal foci. RESULTS:
      We reviewed the medical records of 147 children with GBS and identified 108
      outpatients, including 47 (44%) with occult bacteremia, 42 (39%) with meningitis,
      11 (10%) with nonmeningeal foci, and 8 (7%) with sepsis. Compared with patients
      with sepsis or focal infections, those with occult bacteremia were older (61.1 vs
      39.1 days) and had slightly, although not significantly, higher white blood cell
      (WBC) counts (13 280 +/- 6854 vs 10 688 +/- 8574), but similar degrees of fever.
      Among the 47 patients with occult bacteremia, none died, as compared with 2 of 61
      with serious infections, and fewer had neurologic sequelae (0/47 vs 11/61).
      Patients with occult bacteremia >90 days of age generally had temperatures >39
      degreesC (9/11, mean 39.3 degreesC) and WBC counts >15 000/mm3 (7/10, mean 19
      070/mm3), both of which differed significantly compared with those who were <90
      days of age. Thirty of the 47 patients with occult bacteremia received
      intravenous antibiotics and recovered. One of 8 patients discharged without
      antibiotics and none of 8 with antibiotics developed a focal complication; 1
      discharged patient was lost to follow-up. CONCLUSIONS: Almost one-half of the
      children with GBS disease beyond the immediate neonatal period had occult
      bacteremia. Among 8 untreated patients with bacteremia, 1 developed a focal
      complication. Although the small proportion of children with GBS occult
      bacteremia who were >90 days of age usually had the risk factors of temperature
      >39 degrees C and WBC >15 000/mm3, as seen with occult bacteremia attributable to
      other organisms, the majority of the patients who were younger did not have a
      characteristic clinical syndrome. Prevention of sequelae in these young infants
      will require a low threshold for diagnosis and treatment.

PMID- 9651417
TI  - Asthma in non-inner city Head Start children.
AB  - OBJECTIVE: Asthma is a significant cause of morbidity and mortality in children.
      The objective of this study was to determine whether the federal program Head
      Start in Dane County, Wisconsin, could be used as a mechanism to identify
      preschool-aged children with asthma. DESIGN: Five-year, cross-sectional survey of
      parents with children enrolled in Head Start. METHODS: Investigator-administered
      asthma screening questionnaire to parents of enrolling Head Start children in
      Dane County, Wisconsin. MEASUREMENTS: Asthma prevalence and asthma-related health
      care use, including emergency department visits, hospitalizations, and medication
      usage, were measured using an asthma screening questionnaire developed by
      investigators. RESULTS: Information was gathered on 2215 children. The prevalence
      of physician-diagnosed asthma in the screened children was 15.8%. Parental
      reports of physician-diagnosed asthma were validated in a subset of 133 children,
      with a 98.5% confirmation rate. Independent risk factors for asthma included male
      gender (relative risk, 1.4) and African-American ethnicity (relative risk, 1.4).
      Asthma-related morbidity was substantial with 26.7% of identified children
      hospitalized for asthma and 54.5% with an emergency department visit during their
      lifetime. The majority of children (46.4%) were treated with intermittent, quick
      relief medications (beta-agonists) alone, whereas only 6.1% were on daily, long
      term controller medications. CONCLUSIONS: Asthma screening through a Head Start
      program provides an effective means of targeting preschool-aged children from
      socioeconomic groups at high risk for asthma. Identification of children early in
      the disease course and those at high risk for asthma provides an ideal
      opportunity for the implementation of preventive and therapeutic interventions.

PMID- 9651418
TI  - Maternal asthma and transient tachypnea of the newborn.
AB  - OBJECTIVE: To examine the relationship between transient tachypnea of the newborn
      and asthma complicating pregnancy. DESIGN: Historical cohort analysis. Setting.
      Singleton live deliveries in New Jersey hospitals during 1989 to 1992 (n = 447
      963). PATIENTS: Mother-infant dyads were identified from linked birth certificate
      and maternal and infant hospital claims data. Women with an International
      Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)
      diagnosis code (493) for asthma (n = 2289) were compared with a four-fold larger
      randomly selected control sample (n = 9156) from the remaining pool of women.
      MAIN OUTCOME MEASURE: Transient tachypnea of the newborn. RESULTS: In the overall
      sample, after controlling for the confounding effects of important variables,
      infants of asthmatic mothers were more likely [odds ratio (OR), 1. 79; 95%
      confidence interval (CI), 1.35-2.37] than infants of control mothers to exhibit
      transient tachypnea of the newborn. A stratified analysis by gestational age and
      sex revealed larger and statistically significant associations in term infants
      (OR, 2.02; 95% CI, 1.42-2.87) as opposed to preterm infants (OR, 1.51; 95% CI,
      0.94-2.43) and in male infants (OR, 1.91; 95% CI, 1.35-2.71) as opposed to female
      infants (OR, 1.51; 95% CI, 0.92-2.47). On the other hand, after adjusting for
      important confounding variables, respiratory distress syndrome and maternal
      asthma were not found to be associated (OR, 1.14; 95% CI, 0.79-1.64). CONCLUSION:
      The results of this study provide evidence that maternal asthma is a risk factor
      for transient tachypnea of the newborn and differences in gestational age and sex
      were apparent in this association. The mechanism for this association remains to
      be determined.

PMID- 9651419
TI  - Upstairs downstairs: vertical integration of a pediatric service.
AB  - BACKGROUND: The combined effects of recent changes in health care financing and
      training priorities have compelled academic medical centers to develop innovative
      structures to maintain service commitments yet conform to health care marketplace
      demands. In 1992, a municipal hospital in the Bronx, New York, affiliated with a
      major academic medical center reorganized its pediatric service into a vertically
      integrated system of four interdependent practice teams that provided
      comprehensive care in the ambulatory as well as inpatient settings. One of the
      goals of the new system was to conserve inpatient resources. OBJECTIVE: To
      describe the development of a new vertically integrated pediatric service at an
      inner-city municipal hospital and to test whether its adoption was associated
      with the use of fewer inpatient resources. DESIGN: A descriptive analysis of the
      rationale, goals, implementation strategies, and structure of the vertically
      integrated pediatric service combined with a before-and-after comparison of in
      hospital resource consumption. METHODS: A before-and-after comparison was
      conducted for two periods: the period before vertical integration, from January
      1989 to December 1991, and the period after the adoption of vertical integration,
      from July 1992 to December 1994. Four measures of inpatient resource use were
      compared after adjustment for case mix index: mean certified length of stay per
      case, mean number of radiologic tests per case, mean number of ancillary tests
      per case, and mean number of laboratory tests per case. Difference-in-differences
      in-differences estimators were used to control for institution-wide trends
      throughout the time period and regional trends in inpatient pediatric practice
      occurring across institutions. Results. In 1992, the Department of Pediatrics at
      the Albert Einstein College of Medicine reorganized the pediatric service at
      Jacobi Medical Center, one of its principal municipal hospital affiliates, into a
      vertically integrated pediatric service that combines ambulatory and inpatient
      activities into four interdependent practice teams composed of attending
      pediatricians, allied health professionals, house officers, and social workers.
      The new vertically integrated service was designed to improve continuity of care
      for patients, provide a model of practice for professional trainees, conserve
      scarce resources, and create a clinical research infrastructure. The vertically
      integrated pediatric service augmented the role of attending pediatricians,
      extended the use of allied health professionals from the ambulatory to the
      inpatient sites, established interdisciplinary practice teams that unified the
      care of pediatric patients and their families, and used less inpatient resources.
      Controlling for trends within the study institution and trends in the practice of
      pediatrics across institutions throughout the time period, the vertical
      integration was associated with a decline in 0.6 days per case, the use of 0.62
      fewer radiologic tests per case, 0.21 fewer ancillary tests per case, and 2.68
      fewer laboratory tests per case. CONCLUSIONS: We conclude that vertical
      integration of a pediatric service at an inner-city municipal hospital is
      achievable; conveys advantages of improved continuity of care, enhanced
      opportunities for primary care training, and increased participation of senior
      clinicians; and has the potential to conserve significant amounts of inpatient
      resources.

PMID- 9651420
TI  - Consequences of the delayed diagnosis of ataxia-telangiectasia.
AB  - OBJECTIVES: Ataxia-telangiectasia (AT) is a rare, autosomal recessive
      neurodegenerative disorder in which the diagnosis is obvious when ataxia and
      telangiectasia are both present. However, the diagnosis can be made upon the
      onset of ataxia and before the appearance of telangiectasia if confirmed by
      laboratory tests. Early diagnosis is important for genetic counseling,
      appropriate care, and avoidance of unnecessary tests. The purpose of this study
      is to identify factors responsible for delays in the diagnosis of AT. DESIGN: The
      records of all patients seen at the Ataxia-Telangiectasia Clinical Center from
      July 1, 1995 to April 1, 1997 were reviewed to determine age of onset of gait
      abnormality, recognition of telangiectasia, and diagnosis. RESULTS: In 48
      patients with AT, who were the index cases in their respective families, the
      median age of diagnosis (78 months) occurred after the onset of gait
      abnormalities (15 months) and closely corresponded to the development of
      telangiectasia (72 months). In the majority of cases (34/48), telangiectasia
      appeared before the diagnosis was established. The most common misdiagnosis was
      cerebral palsy (29/48 cases). Twenty-one children (4 with AT) were born after the
      start of symptoms in the index case, but before the establishment of a diagnosis.
      CONCLUSIONS: The term AT, although a concise and memorable label for the
      disorder, is also a barrier to early diagnosis. We recommend the use of routine
      serum alpha-fetoprotein testing for all children with persistent ataxia.

PMID- 9651421
TI  - A phase I/II study of the protease inhibitor indinavir in children with HIV
      infection.
AB  - BACKGROUND: Indinavir, an inhibitor of the human immunodeficiency virus type 1
      (HIV-1) protease, is approved for the treatment of HIV infection in adults when
      antiretroviral therapy is indicated. We evaluated the safety and pharmacokinetic
      profile of the indinavir free-base liquid suspension and the sulfate salt dry
      filled capsules in HIV-infected children, and studied its preliminary antiviral
      and clinical activity in this patient population. In addition, we evaluated the
      pharmacokinetic profile of a jet-milled suspension after a single dose. METHODS:
      Previously untreated children or patients with progressive HIV disease despite
      antiretroviral therapy or with treatment-associated toxicity were eligible for
      this phase I/II study. Three dose levels (250 mg/m2, 350 mg/m2, and 500 mg/m2 per
      dose given orally every 8 h) were evaluated in 2 age groups (<12 years and >/=12
      years). Indinavir was initially administered as monotherapy and then in
      combination with zidovudine and lamivudine after 16 weeks. RESULTS: Fifty-four
      HIV-infected children (ages 3.1 to 18.9 years) were enrolled. The indinavir free
      base suspension was less bioavailable than the dry-filled capsule formulation,
      and therapy was changed to capsules in all children. Hematuria was the most
      common side effect, occurring in 7 (13%) children, and associated with
      nephrolithiasis in 1 patient. The combination of indinavir, lamivudine, and
      zidovudine was well tolerated. The median CD4 cell count increased after 2 weeks
      of indinavir monotherapy by 64 cells/mm3, and this was sustained at all dose
      levels. Plasma ribonucleic acid levels decreased rapidly in a dose-dependent way,
      but increased toward baseline after a few weeks of indinavir monotherapy.
      CONCLUSIONS: Indinavir dry-filled capsules are relatively well tolerated by
      children with HIV infection, although hematuria occurs at higher doses. Future
      studies need to evaluate the efficacy of indinavir when combined de novo with
      zidovudine and lamivudine.

PMID- 9651422
TI  - Family burden and adaptation during the initial year after traumatic brain injury
      in children.
AB  - OBJECTIVE: Traumatic brain injury (TBI) often leads to long-term behavioral and
      cognitive deficits in children. However, little is known about the burden and
      psychosocial morbidity of pediatric TBI for families. The purpose of this study
      was to test the hypothesis that moderate and severe TBI in children has more
      adverse consequences than orthopedic trauma. DESIGN: The sample was comprised of
      children between the ages of 6 and 12 recruited from hospital trauma and
      inpatient units including 53 with severe TBI, 56 with moderate TBI, and 80 with
      orthopedic injuries not involving central nervous system insult. Measures of
      injury-related burden, parental distress, and family functioning were
      administered to the child's primary caregiver at baseline assessment conducted
      soon after injury and at 6- and 12-month follow-ups. Multivariate repeated
      measures analysis of covariance was used to examine group differences in these
      outcomes over time. RESULTS: Caregivers in the severe TBI group reported
      significantly higher levels of family burden, injury-related stress, and parental
      psychological symptoms than caregivers in the orthopedic injury group (ORTHO).
      The groups did not differ with respect to marital distress. Caregivers in the
      severe TBI group were significantly more likely than caregivers in the ORTHO
      group to exceed the clinical cutoff on the Brief Symptom Inventory and to report
      clinically significant levels of family dysfunction at follow-up. CONCLUSIONS:
      The findings suggest that severe TBI is a source of considerable caregiver
      morbidity, even when compared with other traumatic injuries. Caregivers in the
      severe TBI group had persistent stress associated with the child's injury, as
      well as the reactions of other family members, and a relative risk of clinically
      significant psychological symptoms nearly twice that of the ORTHO comparison
      group. These findings underscore the need for interventions that facilitate
      family adaptation after pediatric TBI.

PMID- 9651423
TI  - An epidemiologic profile of children with special health care needs.
AB  - OBJECTIVE: To present an epidemiologic profile of children with special health
      care needs using a new definition of the population developed by the federal
      Maternal and Child Health Bureau. METHODS: We operationalized the new definition
      using the recently released 1994 National Health Interview Survey on Disability.
      Estimates are based on 30 032 completed interviews for children <18 years old.
      The overall response rate was 87%. RESULTS: Eighteen percent of US children <18
      years old in 1994, or 12.6 million children nationally, had a chronic physical,
      developmental, behavioral, or emotional condition and required health and related
      services of a type or amount beyond that required by children generally. This
      estimate includes children with existing special health care needs but excludes
      the at-risk population. Prevalence was higher for older children, boys, African
      Americans, and children from low-income and single-parent households. Children
      with existing special health care needs had three times as many bed days and
      school absence days as other children. An estimated 11% of children with existing
      special health care needs were uninsured, 6% were without a usual source of
      health care, 18% were reported as dissatisfied with one or more aspects of care
      received at their usual source of care, and 13% had one or more unmet health
      needs in the past year. CONCLUSIONS: A substantial minority of US children were
      identified as having an existing special health care need using national survey
      data. Children with existing special health care needs are disproportionately
      poor and socially disadvantaged. Moreover, many of these children face
      significant barriers to health care.

PMID- 9651424
TI  - Neonatal circumcision: when can infants reliably be expected to void?
AB  - OBJECTIVE: Analysis of factors influencing voiding after neonatal circumcision.
      DESIGN: Prospective study of the following factors in 200 circumcised infants:
      birth weight, gestational and postnatal age, type and timing of feeding before
      the procedure, and timing of last voiding before circumcision. RESULTS: There was
      no significant difference in the age when circumcision was performed between
      breastfed infants (6 and 60 hours) and in those formula-fed (8 and 130 hours).
      All infants voided after circumcision, with 75% of breastfed infants and 100% of
      formula-fed infants voiding within 8 hours of the procedure. Breastfed infants
      voided up to 8 hours after the procedure, compared with up to 6 hours in formula
      fed infants, but without a significant difference. The interval between last feed
      before the procedure and the time of voiding after circumcision was significantly
      shorter in formula-fed infants (1 to 9 hours) than in breastfed infants (2 to 21
      hours). The interval between precircumcision and postcircumcision voiding was
      also significantly shorter in formula-fed infants (3 to 12 hours) than in
      breastfed infants (1 to 23 hours). Ninety percent of formula-fed and 64% of
      breastfed infants voided within 10 hours of the last voiding before circumcision.
      No infants aspirated during the procedure, regardless of the time of the last
      feed. No hemorrhagic, infectious, or surgical complications of circumcision were
      observed. CONCLUSION: Postoperative voiding time is predictable. Healthy infants
      who undergo an uncomplicated circumcision can be discharged before voiding
      occurs.

PMID- 9651425
TI  - Female genital mutilation. American Academy of Pediatrics. Committee on
      Bioethics.
AB  - The traditional custom of ritual cutting and alteration of the genitalia of
      female infants, girls, and adolescents, referred to as female genital mutilation
      (FGM), persists primarily in Africa and among certain communities in the Middle
      East and Asia. Immigrants in the United States from areas where FGM is endemic
      may have daughters who have undergone a ritual genital procedure or may request
      that such a procedure be performed by a physician. The American Academy of
      Pediatrics (AAP) believes that pediatricians and pediatric surgical specialists
      should be aware that this practice has serious, life-threatening health risks for
      children and women. The AAP opposes all forms of FGM, counsels its members not to
      perform such ritual procedures, and encourages the development of community
      educational programs for immigrant populations.

PMID- 9651426
TI  - The psychotherapeutic role of the pediatrician, by Milton J. E. Senn, MD,
      Pediatrics, 1948;2:147-152.

PMID- 9651427
TI  - Replacement transfusion as a treatment of erythroblastosis fetalis, by Louis K.
      Diamond, MD, Pediatrics, 1948;2:520-524.

PMID- 9651428
TI  - New concepts of the etiology, diagnosis, and treatment of congenital megacolon
      (Hirschsprung's disease), by Orvar Swenson, MD, et al, Pediatrics, 1949;4:201
      209.

PMID- 9651429
TI  - Humoral antibody formation in infants aged one to three months injected with a
      triple (diphtheria-tetanus-pertussis) alum-precipitated antigen, by William L.
      Bradford, MD, et al, Pediatrics, 1949;4:711-718.

PMID- 9651430
TI  - Treatment of mixed tumors of the kidney in childhood, by Robert E. Gross, MD, and
      Edward B. D. Neuhauser, MD, Pediatrics, 1950;6:843-852.

PMID- 9651431
TI  - Pseudomonas aeruginosa infection as a complication of therapy in pancreatic
      fibrosis (mucoviscidosis), by Sterling D. Garrard, et al, Pediatrics, 1951;8:482.

PMID- 9651432
TI  - Agammaglobulinemia, by Col. Ogden C. Bruton, MC, USA, Pediatrics, 1952;9:722-728.

PMID- 9651433
TI  - Further studies on the treatment of congenital adrenal hyperplasia with
      cortisone: IV. Effect of cortisone and compound B in infants with disturbed
      electrolyte metabolism, by John F. Crigler Jr, MD, Samuel H. Silverman, MD, and
      Lawson Wilkins, MD, Pediatrics, 1952;10:397-413.

PMID- 9651434
TI  - A difference in mortality rate and incidence of kernicterus among premature
      infants allotted to two prophylactic antibacterial regimens, by William A.
      Silverman, et al, Pediatrics, 1956;18:614-624.

PMID- 9651435
TI  - The exposure of children to lead, by J. Julian Chisholm and Harold E. Harrison,
      Pediatrics, 1956:18;943-958.

PMID- 9651436
TI  - The maintenance need for water in parenteral fluid therapy, by Malcolm A.
      Holliday, MD, and William E. Segar, MD, Pediatrics, 1957;19:823-832.

PMID- 9651437
TI  - Test for the concentration of electrolytes in cystic fibrosis of the pancreas
      utilizing pilocarpine by iontophoresis, by Lewis E. Gibson and Robert E. Cooke,
      Pediatrics; 1959;24:545-549.

PMID- 9651438
TI  - Isolation of the respiratory syncytial virus from a patient with pneumonia, by
      Daniel S. Rowe, MD, and Richard H. Michaels, MD, Pediatrics, 1960;26:623-629.

PMID- 9651439
TI  - The alveolar lining layer: a review of studies on its role in pulmonary mechanics
      and in the pathogenesis of atelectasis, by Mary Ellen Avery, MD, Pediatrics,
      1962:30:324-330.

PMID- 9651440
TI  - A simple phenylalanine method for detecting phenylketonuria in large populations
      of newborn infants, by Robert Guthrie and Ada Susi, Pediatrics, 1963;32:318-343.

PMID- 9651441
TI  - Intrauterine growth as estimated from liveborn birth-weight data at 24 to 42
      weeks of gestation, by Lula O. Lubchenco et al, Pediatrics, 1963;32:793-800.

PMID- 9651442
TI  - Reactions to the threatened loss of a child: a vulnerable child syndrome, by
      Morris Green, MD, and Albert A. Solnit, MD, Pediatrics, 1964;34:58-66.

PMID- 9651443
TI  - Studies in acute iron poisoning. I. Desferrioxamine In the treatment of acute
      iron poisoning: clinical observations, experimental studies, and theoretical
      considerations, by Charles F. Whitten et al, Pediatrics, 1965;36:322-335; and
      Studies in acute iron poisoning. II. Further observations on desferrioxamine in
      the treatment of acute experimental iron poisoning, by Charles F. Whitten et al,
      Pediatrics, 1966;38:102-110.

PMID- 9651444
TI  - Child development: a basic science for pediatrics, by Julius B. Richmond, MD,
      Pediatrics, 1967;39:649-658.

PMID- 9651445
TI  - A program to increase health care for children: the pediatric nurse practitioner
      program, by Henry K. Silver, MD, Loretta C. Ford, EdD, and Susan G. Stearly, MS,
      Pediatrics, 1967;39:756-760.

PMID- 9651446
TI  - Antenatal detection of hereditary disorders, by Henry L. Nadler, MD, Pediatrics,
      1968;42:912-918.

PMID- 9651447
TI  - A controlled trial of antepartum glucocorticoid treatment for prevention of the
      respiratory distress syndrome in premature infants, by G. C. Liggins, MB, PhD,
      FRCOG, and R. N. Howie, MB, MRACP, Pediatrics, 1972;50:515-525.

PMID- 9651448
TI  - Responses of children immunized with capsular polysaccharide of Hemophilus
      influenzae type b, by David H. Smith, MD, et al, Pediatrics, 1973;52:637-644; and
      Haemophilus influenzae type b capsular polysaccharide vaccine in children: a
      double-blind field study of 100 000 vaccinees 3 months to 5 years of age in
      Finland, by Heikki Peltola, MD et al, Pediatrics, 1977;60:730-737.

PMID- 9651449
TI  - Tap water scald burns in children, by K. W. Feldman, R. T. Schaller, J. A.
      Feldman, and M. McMillon, Pediatrics, 1978;62:1-7.

PMID- 9651450
TI  - Report of the New England Regional Infant Cardiac Program, by Donald C. Fyler,
      MD, Pediatrics, 1980;65(suppl):375-461.

PMID- 9651451
TI  - Apgar scores as predictors of chronic neurologic disability, by Karin B. Nelson,
      MD, and Jonas H. Ellenberg, PhD, Pediatrics, 1981;68:36-44.

PMID- 9651452
TI  - Aerosol beclomethasone dipropionate compared with theophylline as primary
      treatment of chronic, mild to moderately severe asthma in children, by David G.
      Tinkelman, MD, et al, Pediatrics, 1993;92:64-77.

PMID- 9651453
TI  - Resuscitation of asphyxiated newborn infants with room air or oxygen: an
      international controlled trial: the Resair 2 study.
AB  - OBJECTIVE: Birth asphyxia represents a serious problem worldwide, resulting in
      approximately 1 million deaths and an equal number of serious sequelae annually.
      It is therefore important to develop new and better ways to treat asphyxia.
      Resuscitation after birth asphyxia traditionally has been carried out with 100%
      oxygen, and most guidelines and textbooks recommend this; however, the scientific
      background for this has never been established. On the contrary, theoretic
      considerations indicate that resuscitation with high oxygen concentrations could
      have detrimental effects. We have performed a series of animal studies as well as
      one pilot study indicating that resuscitation can be performed with room air just
      as efficiently as with 100% oxygen. To test this more thoroughly, we organized a
      multicenter study and hypothesized that room air is superior to 100% oxygen when
      asphyxiated newborn infants are resuscitated. METHODOLOGY: In a prospective,
      international, controlled multicenter study including 11 centers from six
      countries, asphyxiated newborn infants with birth weight >999 g were allocated to
      resuscitation with either room air or 100% oxygen. The study was not blinded, and
      the patients were allocated to one of the two treatment groups according to date
      of birth. Those born on even dates were resuscitated with room air and those born
      on odd dates with 100% oxygen. Informed consent was not obtained until after the
      initial resuscitation, an arrangement in agreement with the new proposal of the
      US Food and Drug Administration's rules governing investigational drugs and
      medical devices to permit clinical research on emergency care without the consent
      of subjects. The protocol was approved by the ethical committees at each
      participating center. Entry criterion was apnea or gasping with heart rate <80
      beats per minute at birth necessitating resuscitation. Exclusion criteria were
      birth weight <1000 g, lethal anomalies, hydrops, cyanotic congenital heart
      defects, and stillbirths. Primary outcome measures were death within 1 week
      and/or presence of hypoxic-ischemic encephalopathy, grade II or III, according to
      a modification of Sarnat and Sarnat. Secondary outcome measures were Apgar score
      at 5 minutes, heart rate at 90 seconds, time to first breath, time to first cry,
      duration of resuscitation, arterial blood gases and acid base status at 10 and 30
      minutes of age, and abnormal neurologic examination at 4 weeks. The existing
      routines for resuscitation in each participating unit were followed, and the
      ventilation techniques described by the American Heart Association were used as
      guidelines aiming at a frequency of manual ventilation of 40 to 60 breaths per
      minute. RESULTS: Forms for 703 enrolled infants from 11 centers were received by
      the steering committee. All 94 patients from one of the centers were excluded
      because of violation of the inclusion criteria in 86 of these. Therefore, the
      final number of infants enrolled in the study was 609 (from 10 centers), with 288
      in the room air group and 321 in the oxygen group. Median (5 to 95 percentile)
      gestational ages were 38 (32.0 to 42.0) and 38 (31.1 to 41.5) weeks (NS), and
      birth weights were 2600 (1320 to 4078) g and 2560 (1303 to 3900) g (NS) in the
      room air and oxygen groups, respectively. There were 46% girls in the room air
      and 41% in the oxygen group (NS). Mortality in the first 7 days of life was 12.2%
      and 15.0% in the room air and oxygen groups, respectively; adjusted odds ratio
      (OR) = 0.82 with 95% confidence intervals (CI) = 0.50-1.35. Neonatal mortality
      was 13.9% and 19.0%; adjusted OR = 0. 72 with 95% CI = 0.45-1.15. Death within 7
      days of life and/or moderate or severe hypoxic-ischemic encephalopathy (primary
      outcome measure) was seen in 21.2% in the room air group and in 23.7% in the
      oxygen group; OR = 0.94 with 95% CI = 0.63-1.40. (ABSTRACT TRUNCATED)

PMID- 9651454
TI  - Airbag injuries in infants and children: a case report and review of the
      literature.
AB  - Airbags have saved an estimated 2620 lives as of November 1997. However, airbags
      also have caused a number of injuries and deaths and have received a lot of
      publicity from the NHTSA and the media as a result. The majority of the injuries
      have occurred when seat belts and shoulder harnesses were not used properly in
      conjunction with airbags. This article describes an injury that apparently
      occurred despite use of an age-appropriate, state-of-the-art child protection
      seat.

PMID- 9651455
TI  - Reducing risks to children in vehicles with passenger airbags.
AB  - This review examines the risk that passenger airbags pose for children and
      discusses behavioral and technologic measures aimed at protecting children from
      airbag deployment. Although airbags reduce fatal crash injuries among adult
      drivers and passengers, this safety technology increases mortality risk among
      children younger than age 12. The magnitude of the risk is multiplied when
      children are unrestrained or restrained improperly. As new vehicles are resold to
      buyers who tend to be less safety-conscious than new car owners, the number of
      children endangered by passenger airbag deployment may increase. For vehicles
      already in the fleet, strong measures are required to secure children in the rear
      seat and increase the proper use of appropriate restraint systems through police
      enforcement of laws. One promising strategy is to amend child passenger safety
      laws to require that parents secure children in the rear seats. For future
      vehicles, a mandatory performance standard should be adopted that suppresses
      airbag deployment automatically if a child is located in the front passenger
      seat. Other promising improvements in airbag design also are discussed. Major
      changes in passenger airbag design must be evaluated in a broad analytical
      framework that considers the welfare of adults as well as children.

PMID- 9651456
TI  - Childhood obesity, adipose tissue distribution, and the pediatric practitioner.
AB  - The prevalence of pediatric obesity is increasing in the United States. Sequelae
      from pediatric obesity are increasingly being seen, and long-term complications
      can be anticipated. Obesity is the most common cause of abnormal growth
      acceleration in childhood. Obesity in females is associated with an early onset
      of puberty and early menarche. Puberty is now occurring earlier in females than
      in the past, and this is probably related either directly or indirectly to the
      population increase in body weight. The effect of obesity on male pubertal
      maturation is more variable, and obesity can lead to both early and delayed
      puberty. Pubertal gynecomastia is a common problem in the obese male. Many of the
      complications of obesity seen in adults appear to be related to increased
      accumulation of visceral fat. It has been proposed that subcutaneous fat may be
      protective against the adverse effects of visceral fat. Males typically
      accumulate fat in the upper segment of the body, both subcutaneously and
      intraabdominally. In females, adiposity is usually subcutaneous and is found
      particularly over the thighs, although visceral fat deposition also occurs.
      Gender-related patterns of fat deposition become established during puberty and
      show significant familial associations. There are no reliable means for assessing
      childhood and adolescent visceral fat other than radiologically. Noninsulin
      dependent diabetes is being seen more commonly in the pediatric population.
      Diabetes and impaired glucose tolerance are noted particularly in obese children
      with a family history of diabetes. In this situation, a glucose tolerance test
      may be indicated, even in the presence of fasting normoglycemia.
      Hypertriglyceridemia and low high-density lipoprotein-cholesterol levels are the
      primary lipid abnormalities of obesity and are related primarily to the amount of
      visceral fat. Low-density lipoprotein-cholesterol levels are not typically
      elevated in simple obesity. The offspring of parents with early coronary disease
      tend to be obese. Very low-density lipoprotein and intermediate-density
      lipoprotein particles, which are small in size, may be important in atherogenesis
      but they cannot be identified in a fasting lipid panel. The propensity to
      atherogenesis cannot be interpreted readily from a fasting lipid panel, which
      therefore should be interpreted in conjunction with a family history for coronary
      risk factors. Hypertriglyceridemia may be indicative of increased visceral fat,
      familial combined hyperlipidemia, familial dyslipidemic hypertension, impaired
      glucose tolerance, or diabetes. Almost half of adult females with polycystic
      ovary syndrome are obese and many have a central distribution of body fat. This
      condition frequently has its origins in adolescence. It is associated with
      increased androgen secretion, hirsutism, menstrual abnormalities, and
      infertility, although these may not be present in every case. Adults with
      polycystic ovary syndrome adults are hyperlipidemic, have a high incidence of
      impaired glucose tolerance and noninsulin-dependent diabetes, and are at
      increased risk for coronary artery disease. Weight reduction and lipid lowering
      therefore are an important part of therapy. Obstructive sleep apnea with daytime
      somnolence is a common problem in obese adults. Pediatric studies suggest that
      obstructive sleep apnea occurs in approximately 17% of obese children and
      adolescents. Sleep disorders in the obese may be a major cause of learning
      disability and school failure, although this remains to be confirmed. Symptoms
      suggestive of a sleep disorder include snoring, restlessness at night with
      difficulty breathing, arousals and sweating, nocturnal enuresis, and daytime
      somnolence. Questions to exclude obstructive sleep apnea should be part of the
      history of all obese children, particularly for the morbidly obese. For many
      children and adolescents with mild obesity, and particularly for females, one can
      speculate that obesity may not be a great health risk

PMID- 9651458
TI  - Clinical features of acute allergic reactions to peanut and tree nuts in
      children.
AB  - BACKGROUND: Peanut (PN) and tree nut (TN) allergies are potentially life
      threatening, rarely outgrown, and appear to be increasing in prevalence. However,
      there is relatively little reported about the clinical features of acute
      reactions to these foods and their potential association. OBJECTIVE: To describe
      the clinical features of acute reactions during initial and subsequent accidental
      ingestions of PN and TN among children with a history of at least one acute
      allergic reaction to these foods. DESIGN: Questionnaire survey, examination, and
      serologic testing for specific IgE antibody of patients with convincing histories
      of acute reactions (at least one organ system involved within 60 minutes of
      ingestion) to PN or TN. RESULTS: A total of 122 patients (63% males; median age,
      8 years at time of study) had acute reactions; 68 had reactions only to PN, 20
      only to TN, and 34 to both PN and TN. Of those reacting to TN, 34 had reactions
      to one, 12 to two, and 8 to three or more different TN, the most common being
      walnut, almond, and pecan. Initial reactions usually occurred at home (median
      age, 24 months for PN and 62 months for TN) and were considered to result from a
      first exposure in 72% of cases. Eighty-nine percent of the reactions involved the
      skin (urticaria, angioedema), 52% the respiratory tract (wheezing, throat
      tightness, repetitive coughing, dyspnea), and 32% the gastrointestinal tract
      (vomiting, diarrhea). Two organ systems were affected in 31% of initial
      reactions, and all three in 21% of reactions. Thirty-eight of 190 first reactions
      to PN or TN were treated with epinephrine. Accidental ingestions occurred in 55%
      of PN-allergic children (average of two accidents per patient with an accidental
      ingestion) and in 30% of TN-allergic children over a median period of 5.5 years.
      On average, symptoms after accidental exposure were generally similar to those at
      initial exposure. Accidents occurred commonly in school but also at home and in
      restaurants. Modes of accidental ingestion included sharing food, hidden
      ingredients, cross-contamination, and school craft projects using peanut butter.
      Eighty-three percent of the children were breastfed, with >90% of the mothers
      ingesting PN and at least one TN during lactation. Among patients reporting no
      history of exposure (>60% of patients for each TN), IgE antibodies were found to
      a particular TN in 50% to 82% of patients and to PN in 100% of patients.
      CONCLUSIONS: Acute allergic reactions to PN occur early in life. PN and TN
      allergic reactions coexist in one third of PN-allergic patients, frequently occur
      on first known exposure, and may be life-threatening, requiring emergency
      treatment. Accidental ingestions are common, occur frequently outside of the
      home, and often require emergency treatment. Consequently, early diagnosis
      followed by education on avoidance and treatment measures (including self
      administered epinephrine) is imperative.

PMID- 9651457
TI  - Incidence of passive exposure to crack/cocaine and clinical findings in infants
      seen in an outpatient service.
AB  - OBJECTIVES: Passive exposure to crack/cocaine and the associated clinical
      symptoms may present a significant health risk to very young infants and
      children. This study was designed to determine the incidence of cocaine exposure,
      presumed to be passive, in ill infants younger than 1 year of age, using a
      threshold of detection for cocaine and/or its major metabolite, benzoylecognine
      (BE), that is lower than the current National Institute on Drug Abuse standard.
      The study also investigates the morbidity associated with passive cocaine
      exposure in this population. METHODS: We prospectively obtained 124 samples of
      urine from 122 children younger than 1 year of age for routine clinical
      indications from the emergency department at Yale-New Haven Hospital. Samples
      were analyzed by radioimmunoassay (RIA) for cocaine, with cross-reactivity for
      BE. The presence of BE in a portion of the RIA-positive samples also was detected
      in additional analyses by enzyme-multiplied immunoassay technique or by gas
      chromatography-mass spectrometry. A chart review was conducted on all 122
      patients by reviewers blind to the urine toxicology results. Presenting
      complaints, symptoms, vital signs, and diagnosis were obtained for all visits
      before the first birthday. Birth history, including maternal drug history and
      birth weight, demographics, and number of medical visits in the first year, were
      recorded as well. RESULTS: Of the 124 samples, 45 (36.3%) were positive (>/=50
      ng/mL of BE equivalents) for cocaine and/or cocaine metabolite by RIA testing.
      The positive results, determined by RIA, were highly correlated with patients who
      had lower and upper respiratory symptoms and sought medical care more often.
      CONCLUSIONS: The incidence of unsuspected, passive cocaine exposure in ill
      infants seeking medical care primarily through an emergency service may be as
      high as 1 in 3 to 6 infants from our predominantly inner city population. Current
      immunoassay methods, specific for BE, and their routine threshold of detection
      (200 to 300 ng/mL) may not be sensitive enough to detect cocaine and BE in the
      urine samples of children younger than 1 year of age who are exposed passively.
      The development of upper and lower respiratory symptoms is correlated
      significantly with positive urine results in this study. The increased use of
      health care resources correlated with passive cocaine exposure in this sample may
      serve as an indirect marker for the increased medical needs of these infants.

PMID- 9651459
TI  - Kawasaki disease in the older child.
AB  - OBJECTIVES: To determine the prevalence of Kawasaki disease in older children and
      to evaluate its clinical presentation, time to diagnosis, and outcome in
      comparison with younger patients with the disease. METHODOLOGY: A retrospective
      analysis of all patients discharged with a diagnosis of Kawasaki disease at a
      pediatric tertiary care hospital over a 12-year period. RESULTS: A total of 133
      patients were included in this study; 7.5% were 9 years of age or older at the
      time of illness. Patients were grouped by age: infants included children age 1 to
      8 years of age and children 9 years of age or older. Older children had a higher
      frequency of abnormal cardiovascular physical examination (50%) versus children
      (6%) and infants (10%). The older age group and the infants had a higher
      prevalence of coronary artery abnormalities and poor left ventricular function
      than did the 1- to 8-year-olds. Eighty percent of the older children had coronary
      arteries that were either dilated or aneurysmal, and 30% demonstrated left
      ventricular dysfunction on initial echocardiography. The number of days to
      diagnosis after meeting the diagnostic criteria was 5.8 +/- 2.3 for infants, 5.2
      +/- 1.5 for older children, and 1.9 +/- 0.3 for children. Older children had a
      complicated course of Kawasaki disease compared with younger patients.
      CONCLUSION: We found a higher prevalence of older children with Kawasaki disease
      at our center than has previously been reported. Older patients, as well as
      infants, had a higher rate of coronary artery abnormalities than did the children
      between 1 and 8 years of age. Older age at the time of illness or a delay in
      treatment may be important factors in determining cardiac involvement in Kawasaki
      disease.

PMID- 9651460
TI  - Early language development in children exposed to or infected with human
      immunodeficiency virus.
AB  - OBJECTIVES: To compare language development in infants and young children with
      human immunodeficiency virus (HIV) infection to language development in children
      who had been exposed to HIV but were uninfected, and (among subjects with HIV
      infection) to compare language development with cognitive and neurologic status.
      DESIGN: Prospective evaluation of language development in infected and in exposed
      but uninfected infants and young children. SETTING: Pediatric Infectious Disease
      Clinic, State University of New York-Health Science Center at Syracuse. SUBJECTS:
      Nine infants and young children infected with HIV and 69 seropositive but
      uninfected infants and children, age 6 weeks to 45 months. RESULTS: Mean Early
      Language Milestone Scale, 2nd edition (ELM-2) Global Language scores were
      significantly lower for subjects with HIV infection, compared with uninfected
      subjects (89.3 vs 96.2, Mann-Whitney U test). The proportion of subjects scoring
      >2 SD below the mean on the ELM-2 on at least one occasion also was significantly
      greater for subjects with HIV infection, compared with uninfected subjects (4 of
      9 infected subjects, but only 5 of 69 uninfected subjects; Fisher's exact test).
      Seven of the 9 subjects with HIV infection manifested deterioration of language
      function. Four manifested unremitting deterioration; only 1 of these 4
      demonstrated unequivocal abnormality on neurologic examination. Three subjects
      with HIV infection and language deterioration showed improvement in language
      almost immediately after the initiation of antiretroviral drug treatment.
      Magnetic resonance imaging or computed tomography of the brain were performed in
      6 of 7 infected subjects with language deterioration, and findings were normal in
      all 6. ELM-2 Global Language scaled scores showed good agreement with the Bayley
      Mental Developmental Index or the McCarthy Global Cognitive Index (r = 0. 70).
      Language deterioration, or improvement in language after initiation of drug
      therapy, coincided with or preceded changes in global cognitive function, at
      times by intervals of up to 12 months. CONCLUSIONS: Language deterioration occurs
      commonly in infants and young children with HIV infection, is seen frequently in
      the absence of abnormalities on neurologic examination or central nervous system
      imaging, and may precede evidence of deterioration in global cognitive ability.
      Periodic assessment of language development should be added to the developmental
      monitoring of infants and young children with HIV infection as a means of
      monitoring disease progression and the efficacy of drug treatment.

PMID- 9651461
TI  - Experiment of nurture: ablatio penis at 2 months, sex reassignment at 7 months,
      and a psychosexual follow-up in young adulthood.
AB  - Guidelines of psychosexual management for infants born with physical intersex
      conditions are intended to assist physicians and parents in making decisions
      about sex of assignment and rearing including the following: 1) sex assignment
      should be to the gender that carries the best prognosis for good reproductive
      function, good sexual function, normal-looking external genitalia and physical
      appearance, and a stable gender identity; 2) the decision regarding sex
      assignment should be made as early as possible, preferably during the newborn
      period, with an upper age limit for reversal of an initial sex assignment no
      later than 18 to 24 months; and 3) there should be minimal uncertainty and
      ambiguity on the part of parents and professionals regarding the final decision
      about sex assignment and rearing. J. Money used these guidelines in a case of a
      biologically normal male infant (one of a pair of monozygotic twins) whose penis
      was accidentally ablated during a circumcision at the age of 7 months. The
      decision to reassign the infant boy to the female sex and to rear him as a girl
      was made at 17 months, with surgical castration and initial genital
      reconstruction occurring at 21 months. Money reported follow-up data on this
      child through the age of 9 years. Although the girl was described as having many
      "tomboyish" behavioral traits, a female gender identity had apparently
      differentiated. Thus, it was concluded that gender identity is sufficiently
      incompletely differentiated at birth as to permit successful assignment of a
      genetic male as a girl, in keeping with the experiences of rearing. Subsequent
      follow-up by other investigators reported that by early adolescence the patient
      had rejected the female identity and began to live as a male at the age of 14
      years. In adulthood, the patient recalled that he had never felt comfortable as a
      girl, and his mother reported similar recollections. At age 25, the patient
      married a woman and adopted her children. The patient reported exclusive sexual
      attraction to females. The present case report is a long-term psychosexual follow
      up on a second case of ablatio penis in a 46 XY male. During an electrocautery
      circumcision at the age of 2 months, the patient sustained a burn of the skin of
      the entire penile shaft, and the penis eventually sloughed off. At age 7 months,
      the remainder of the penis and the testes were removed. By age 7 months, if not
      earlier, the decision was made to reassign the patient as a female and to raise
      the infant as a girl. The patient was interviewed on two occasions: at 16 years
      and twice while in the hospital for additional surgery at 26 years of age. At
      ages 16 and 26, the patient was living socially as a woman and denied any
      uncertainty about being a female. During childhood, the patient recalled that she
      self-identified as a "tomboy" and enjoyed stereotypically masculine toys and
      games; however, the patient also recalled that her favorite playmates were
      usually girls and that her best friend was always a girl. When seen at age 16,
      the patient had been admitted to the hospital for vaginoplasty. At that time, she
      wished to proceed with the further repair of her genitalia to make them suitable
      for sexual intercourse with males. At age 26, the patient returned to the
      hospital for further vaginoplasty. Regarding the patient's sexual orientation,
      she was attracted predominantly to women in fantasy, but had had sexual
      experiences with both women and men. At the time of the second surgery, she was
      in a relationship with a man and wished to be able to have intercourse. The
      patient's self-described sexual identity was "bisexual." After surgery at age 26
      years, the patient developed a rectovaginal fistula. Within a few months of the
      surgery, the patient and her male partner separated for reasons other than the
      patient's physical problems. The patient subsequently began living with a new
      partner, a woman, in a lesbian relationship. The psychosexual development of our
      patient was bot the other patient was married to a woman. Our patient had a
      "bisexual" sexual identity; the other patient had a "heterosexual" sexual
      identity. The patients were similar in that they had a childhood history of
      "tomboyism." Our patient was predominantly sexually attracted to women; the other
      patient was exclusively sexually attracted to women. Our patient had sexual
      experiences with both women and men; the other patient had sexual experiences
      only with women. The most plausible explanation of our patient's differentiation
      of a female gender identity is that sex of rearing as a female, beginning at
      around age 7 months, overrode any putative influences of a normal prenatal
      masculine sexual biology. Because cases of ablatio penis in infancy are so rare
      and long-term follow-up data are scant, it is obviously impossible to know
      whether our patient or the previous case would be more typical of the
      psychosexual outcome in a larger sample of such individuals. However, our case
      suggests that it is possible for a female gender identity to differentiate in a
      biologically "normal" genetic male. At present, however, the clinical literature
      is deeply divided on the best way to manage cases of traumatic loss of the penis
      during infancy. Further study is clearly required to decide on the optimal model
      of psychosocial and psychosexual management for affected individuals.

PMID- 9651462
TI  - A comparison of supination/flexion to hyperpronation in the reduction of radial
      head subluxations.
AB  - OBJECTIVE: To compare supination at the wrist followed by flexion at the elbow
      (the traditional reduction technique) to hyperpronation at the wrist in the
      reduction of radial head subluxations (nursemaid's elbow). MATERIALS AND METHODS:
      This prospective, randomized study involved a consecutive sampling of children
      younger than 6 years of age who presented to one of two urban pediatric emergency
      departments and two suburban pediatric ambulatory care centers with a clinical
      diagnosis of radial head subluxation. Patients were randomized to undergo
      reduction by one of the two methods and were followed every 5 minutes for return
      of elbow function. The initial procedure was repeated if baseline functioning did
      not return 15 minutes after the initial reduction attempt. Failure of that
      technique 30 minutes after the initial reduction attempt resulted in a cross-over
      to the alternate method of reduction. The alternate procedure was repeated if
      baseline functioning did not return 15 minutes after the alternate procedure was
      attempted. If the patient failed both techniques, radiography of the elbow was
      performed. RESULTS: A total of 90 patients were enrolled in the study. Five
      patients were removed from further analysis secondary to a final diagnosis of
      fracture, 84 were reduced successfully, and 1 failed both techniques. Demographic
      characteristics of each group were similar. Thirty-nine of 41 patients (95%)
      randomized to hyper-pronation were reduced successfully on the first attempt
      versus 34 of 44 patients (77%) randomized to supination. Two patients in the
      hyperpronation group required two attempts versus 10 patients in the supination
      group. Hyperpronation was more successful; 40 of 41 patients (97.5%) in the
      hyperpronation group were reduced successfully versus 38 of 44 patients (86%) in
      the supination group. Of the 6 patients who crossed over from supination to
      hyperpronation, 5 were reduced on the first attempt and 1 was reduced on the
      second attempt. CONCLUSIONS: In the reduction of radial head subluxations, the
      hyperpronation technique required fewer attempts at reduction compared with
      supination, was successful more often than supination, and was often successful
      when supination failed.

PMID- 9651463
TI  - Maternal cigarette smoking and child psychiatric morbidity: a longitudinal study.
AB  - OBJECTIVE: Previous studies have linked maternal smoking during pregnancy with
      behavioral disturbance in children. However, additional evidence is needed to
      address the causality of the relationship. The present study analyses result from
      an Australian cohort of 5342 5-year-old children whose mothers were recruited
      early in pregnancy. METHODS: Smoking history was gathered for prepregnancy, first
      clinic visit (FCV), late pregnancy, and when the child was 6 months and 5 years
      of age. Behavior problems at the age of 5 were assessed using a modified Child
      Behavior Check List (CBCL) shown to have high agreement with the complete CBCL.
      This resulted in the formation of three scales: internalizing; social,
      attentional and thought; and externalizing behavior problems, which were then
      dichotimized at the 90th percentile in each case. Logistic regression was used to
      model these outcomes as a function of maternal smoking at five time points during
      which it was assessed. A series of models explored the effect of additional
      adjustment for confounding. The predictors of attrition (29.5%) throughout the
      cohort were also identified by multivariate modeling. RESULTS: The final analysis
      was carried out on a cohort of mother-child pairs for whom data and child
      behavior outcomes were complete. The mean age of children was 5 years, 6 months
      with a range from 4 to 6 years. The mean age of mothers at the time of birth of
      the child was 25 years, with a range from 13 to 47 years. Mothers lost to follow
      up were more likely to be younger, single, and less well-educated than those who
      continued participation, although maternal smoking was not an independent
      determinant. Unadjusted analyses showed strong associations between externalizing
      child behavior and maternal smoking during pregnancy and at the 5-year follow-up,
      with relative risks (RRs) up to 2.6 for children of women smoking at least 20
      cigarettes per day at the first antenatal clinic visit. A clear dose-response
      relationship existed in most relationships with higher levels of smoking being
      associated with higher rates of externalizing behavior problems. Weaker
      relationships occurred for internalizing behavior and social, attentional and
      thought behavior problems. Multivariate analysis of the timing in more detail
      that the association between maternal smoking and child behavior problems
      persisted, although the evidence for dose-response diminished. Moreover, it was
      primarily associated with smoking as determined by questions asked at the FCV (RR
      = 1.52, 2.03, 2.16) for 1 to 9, 10 to 19, and >/=20 cigarettes per day,
      respectively, compared with nonsmoking and secondarily by smoking determined at
      the 5-year follow-up (RR = 1.52, 1.87, 1.29) for 1 to 9, 10 to 19, and >/=20
      cigarettes per day respectively, compared with nonsmoking. This association
      appeared to be independent of a wide range of possible confounders such as
      maternal age, education, social class, marital status and mental health,
      gestation at FCV, complications during pregnancy, the child's sex, gestational
      age at birth, and age at last follow-up. Adjustments were also made for the
      mother's employment since birth, family structure, and maternal mental health at
      the time of the CBCL assessment. Associations between externalizing behavior
      problems and maternal smoking at other times, and those between other behavioral
      problems examined and maternal smoking were not significant. CONCLUSION: Although
      previous studies have found evidence for an association between maternal smoking
      and child behavior problems, the strength of this study lies in its size, its
      detailed and consistent measurement of maternal smoking, and its ability to
      control for many social and biological factors linked to maternal smoking and
      child behavior. (ABSTRACT TRUNCATED)

PMID- 9651464
TI  - Further delineation of aortic dilation, dissection, and rupture in patients with
      Turner syndrome.
AB  - OBJECTIVE: Although cardiovascular malformations (CVMs) are well-recognized
      congenital anomalies in Turner syndrome, aortic dilation and dissection are less
      common and less familiar. Most of the relevant literature is limited to single
      cases reports or small series. We sought to increase the information available
      about the frequency and characteristics of aortic dilation in patients with
      Turner syndrome. DESIGN: A 1-page survey of cardiac abnormalities, including
      aortic dilation, was mailed to approximately 1000 (1040 verified) members of the
      Turner Syndrome Society as an enclosure in the June 1997 newsletter. We also
      conducted a literature review. PARTICIPANTS: A total of 245 patients or families
      of patient members of the Turner Syndrome Society responded to the survey (
      approximately 24% response rate). RESULTS: A CVM was reported in 120 of 232 (52%)
      respondents to this questionnaire. Obstructive lesions of the left side of the
      heart predominated and included bicuspid aortic valve (38%) and coarctation
      (41%). Aortic dilation was reported in at least 15 of 237 respondents (6.3%; 95%
      confidence interval: 3.6%-10.3%); 2 of 15 (13%) had dissection. Twelve of 15
      (80%) patients had an associated risk factor for aortic dilation such as a CVM or
      hypertension. The 3 (20%) patients who did not have a CVM or hypertension were
      all younger than 21 years. In the entire group with aortic dilation, 10 of 15
      (67%) patients were younger than 21 years. All patients with aortic dilation had
      involvement of the ascending aorta, and 2 had additional involvement of the
      descending aorta distal to a repaired coarctation. An update of the literature
      revealed 68 patients with aortic dilation, dissection, or rupture. An associated
      CVM or hypertension was reported in 53 of 59 (90%) informative patients. At least
      6 (10%) had no predisposing risk factor (information was inadequate for 9 of 68
      patients). The following patterns of aortic involvement were identified:
      ascending +/- descending aorta with coarctation (14); ascending +/- descending
      aorta without coarctation (39); descending aorta with coarctation (3); descending
      thoracic or abdominal aorta without coarctation (4); and unspecified (8).
      Dissection or rupture was reported in 42/68 (62%). Two reported patients died
      suddenly from aortic dissection in the third trimester of assisted pregnancy. At
      least 20 (29%) patients were younger than 21 years. One of the 6 (17%) patients
      with isolated aortic dilation was in this younger group. CONCLUSIONS: More
      information is needed about the frequency and natural history of aortic dilation
      in Turner syndrome. This work contributes new patient data and increases the
      literature review. Despite the well-recognized limitations of self-reporting,
      this survey detected aortic dilation with or without dissection in approximately
      6% of patients with Turner syndrome. Although rare, this is a potentially
      catastrophic occurrence, warranting greater awareness among health professionals.
      In this study and the literature, the vast majority of patients with aortic
      dilation have an associated risk factor such as a CVM, typically bicuspid aortic
      valve or coarctation, or systemic hypertension. These patients represent a higher
      risk group that should be followed appropriately, usually under the direction of
      a cardiologist. Patients undergoing assisted pregnancy also should be evaluated
      closely. It is generally accepted that at the time of diagnosis of Turner
      syndrome, all patients should have a complete cardiology evaluation including
      echocardiography. The small number of patients with aortic dilation without a
      CVM, who would not be under the long-term care of a cardiologist, makes it
      prudent to screen all patients with Turner syndrome for this potentially lethal
      abnormality. The specific timing for this screening is controversial. Our
      recommendations for prospective imaging do not represent a rigid standard of
      care.

PMID- 9651465
TI  - Desensitization to pancreatic enzyme intolerance in a child with cystic fibrosis.
AB  - OBJECTIVE: Pancreatic enzyme is essential in the treatment of cystic fibrosis
      (CF), but intolerance to it occasionally occurs. We encountered a child who was
      intolerant to multiple commercially available preparations of pancreatic enzymes
      and, hence, desensitization was attempted, with success. CASE PRESENTATION: A 33
      month-old girl was diagnosed with CF at 6 months of age. Initially, she was
      started on Pancrease MT 16, which was subsequently discontinued because fecal fat
      studies were normal and she seemed to do well on Nutramigen and vitamin
      supplements. At 29 months of age, she developed diarrhea with bulky stools and
      weight loss. A fecal fat 72-hour study revealed a coefficient of absorption of
      50%. She was treated with Pancrease MT 16, but had consistent vomiting 1 to 2
      hours after administration of enzymes. The vomiting occurred on switching to
      different pancreatic enzymes preparations, ie, Creon 10, Viokase, and Pancrease
      MT 16. Vomiting occurred even with small doses of enzymes disguised in food. She
      had no history suggestive of gastroesophageal reflux, peptic ulcer, or pork
      allergy, and no vomiting on days when enzymes were not given. This was suggestive
      of type I hypersensitivity reaction. Pancreatic enzymes were discontinued, and
      she was given a low-fat, high-carbohydrate diet with satisfactory weight gain.
      METHODS: Double-blind, placebo-controlled titrated oral challenges with
      pancreatic enzymes resulted in definite vomiting within 1 to 1.5 hours after
      challenges with Viokase and Pancrease MT 16, but not with placebo. Rush oral
      desensitization with Viokase solution was attempted, starting with 5 mg, and the
      dose was doubled every 20 minutes, aiming to reach a cumulative dose of 700 mg.
      However, the child vomited when a cumulative dose of 315 mg was reached. Another
      trial of slower desensitization was done using Pancrease MT 16 (1 capsule: 16 000
      U of lipase, 48 000 U of amylase, and 48 000 U of protease), starting with 1/4
      capsule per day, with increments of 1/4 capsule every 3 days, until an entire
      capsule was reached by day 10, then increased by approximately 1/2 capsule every
      4 days until reaching the therapeutic dose of 1 capsule with each meal by day 25.
      RESULTS: The patient tolerated this fairly well and has been on this treatment
      and regular diet for >1 year, without any adverse reaction. This illustrates a
      rare case of gastrointestinal adverse reaction to pancreatic enzymes that was
      treated successfully with desensitization. CONCLUSION: Pancreatic enzyme
      intolerance, although rare, would be a major problem in the management of
      patients with CF. Hence, desensitization would be essential and may be
      accomplished successfully using the protocol described in this report.

PMID- 9651466
TI  - One-week triple therapy with omeprazole, clarithromycin, and nitroimidazole for
      Helicobacter pylori infection in children and adolescents.
AB  - BACKGROUND: Resolution of Helicobacter pylori infection is important in the
      management of peptic ulcer disease and reduces peptic ulcer recurrence in both
      adults and children. Various anti-H pylori treatment regimens have been proposed,
      reflecting the incomplete clinical success of each. A combination of omeprazole,
      clarithromycin, and tinidazole, given for 1 week, has been shown to be highly
      tolerable and effective, achieving a success rate of >90% in the adult
      population. OBJECTIVE: The aim of this study was to evaluate this short-term
      regimen in pediatric and adolescent populations. METHODS: The study group
      consisted of 35 children referred for evaluation of dyspeptic symptoms. They all
      underwent upper gastrointestinal endoscopy, in which H pylori infection was
      confirmed by rapid urease test and/or histologic staining. They were given
      omeprazole (20 mg twice daily), clarithromycin (250 mg twice daily), and
      tinidazole or metronidazole (500 mg twice daily) for 1 week. The patients were
      divided into two groups: those who received the first course of anti-H pylori
      therapy during this study (group 1) and those who had previously received
      standard metronidazole and bismuth combination therapies that failed to eradicate
      H pylori (group 2). Therapeutic efficacy was assessed by a 13C-urea breath test
      performed 4 weeks after completion of treatment. Results. The 35 study patients
      had a mean age of 15.9 years (range, 10 to 19) and included 19 males and 16
      females, of whom 22 were born in Israel and 13 were immigrants from the former
      USSR. There were 27 patients (77. 1%) in group 1 and 8 patients (22.9%) in group
      2. Endoscopic findings were nodular gastritis (14), gastritis (11), gastric ulcer
      (1), duodenal ulcer (5), and duodenitis (4). H pylori resolution was
      significantly higher in group 1 patients (24/27, 88.9%) than in group 2 patients
      (1/8, 12.5%). There was no difference between patients with nodular gastritis and
      those with nonnodular gastritis, and between Israeli-born patients and patients
      born in the former USSR. Compliance in both groups was equally good, and no major
      side effects were recorded. CONCLUSIONS: One-week
      omeprazole/clarithromycin/tinidazole triple therapy is highly tolerable and
      effective for treating H pylori in the pediatric age group, but previous
      treatment failure diminishes the likelihood of success with this regimen.

PMID- 9651467
TI  - Voltage-dependent calcium influx in human sperm assessed by simultaneous optical
      detection of intracellular calcium and membrane potential.
AB  - There are several physiological and pharmacological evidences indicating that
      opening of voltage dependent calcium channels play a crucial role in the
      induction of the acrosome reaction in mammalian sperm. In mature sperm,
      physiological inductors of the acrosome reaction such as ZP3, a zona pellucida
      protein, and the steroid hormone progesterone, induce depolarization and calcium
      influx, which are required for the acrosome reaction. In this paper, we describe
      a voltage-dependent calcium influx present in human sperm. We report an
      experimental procedure that allows measurement of intracellular calcium and
      membrane potential simultaneously using the fluorescent dyes DiSC3(5) and Fura-2.
      We found that in human uncapacitated sperm, depolarization induces a nifedipine
      insensitive calcium influx that, in most cases, was transient. Calcium influx was
      observed in the range of -60 to -15 mV (the range tested). At resting membrane
      potential (around -40 mV), potassium addition depolarized and induced calcium
      influx, but when the depolarization was preceded by a hyperpolarization (induced
      with valinomycin), calcium influx was remarkably enhanced, suggesting that at -40
      mV, channels are in a putative inactivated state. When sperm was incubated in
      medium without calcium, calcium restoration caused calcium influx that depended
      on voltage, and decayed between 1 and 2 min after depolarization. Unlike ram,
      mouse or bovine sperm, in which an alkalinization is required to induce calcium
      influx with potassium, the voltage-dependent calcium influx observed in human
      sperm did not require an increase in internal or external pH. However, we
      observed that ammonium, which increases intracellular pH, enhanced the voltage
      dependent calcium influx about 90%. Furthermore, depolarization by itself caused
      a small increase in intracellular pH suggesting that pH can be regulated by
      membrane potential in human sperm.

PMID- 9651468
TI  - The R8-photoreceptor equivalence group in Drosophila: fate choice precedes
      regulated Delta transcription and is independent of Notch gene dose.
AB  - It has been suggested that lateral specification of cell fate by Notch signaling
      depends on feedback on Notch (N) and Delta (Dl) transcription to establish
      reciprocal distributions of the receptor and its ligand at the protein level. In
      Drosophila neurogenesis the predicted reciprocal protein distributions have not
      been observed. Either this model of lateral specification or the description of N
      and/or Dl protein distributions must be incomplete. We have reexamined R8
      photoreceptor specification in the developing eye to resolve this question for
      this example of lateral specification. N and Dl protein levels were assessed in
      the cell as a whole and at the cell surface, where these proteins were mostly
      found at the intercellular cell junctions. Protein levels did not correspond to
      Notch signaling in wild type. However, Dl transcription and protein levels did
      correlate with altered N signaling in mutant genotypes. Our findings suggest the
      difference relates to the speed of lateral specification in vivo. The time
      required for N signaling to inhibit ato expression was at most 90 min, but
      changes in the Dl protein distribution in mutant genotypes arose more slowly. N
      expression was little regulated by N signaling, but protein encoded by the Nts1
      allele was temperature-sensitive for appearance at the cell surface. Some aspects
      of the pattern of Dl protein appeared to be due to endocytosis. We conclude that
      feedback of N signaling on Dl transcription does occur but is too slow to account
      for the pattern of R8 specification. Studies of ommatidia mosaic for a Notch
      duplication, or for the Nts1 allele at semi-restrictive temperatures, found that
      cells beginning with less N activity were not necessarily predisposed to be
      selected for R8 differentiation. Our data argue that other signals may be
      responsible for the pattern of R8 cell fate allocation by N. Potential relevance
      to other neurogenic regions is discussed.

PMID- 9651469
TI  - Triggerable liposomal fusion by enzyme cleavage of a novel peptide-lipid
      conjugate.
AB  - A novel peptide-lipid sensitive to enzyme cleavage was designed to generate
      liposomes that could be triggered to fuse by enzymatic activation. Covalent
      linkage of dioleoyl phosphatidylethanolamine (DOPE) to an elastase substrate, N
      acetyl-ala-ala-, resulted in a cleavable peptide-lipid (N-Ac-AA-DOPE) with no
      intrinsic fusogenic activity. Cleavage of N-Ac-AA-DOPE and concomitant conversion
      to the fusogenic lipid DOPE could be detected after treatment with human
      leukocyte elastase or proteinase K, two proteases with similar substrate
      specificities. A strategy to utilize this cleavage to trigger fusogenicity was
      tested by modeling the fusion of liposomes containing the expected product of
      complete cleavage. Based on these results liposomes were designed to contain N-Ac
      AA-DOPE, DOTAP, and PE in the ratio of 15/15/70. These liposomes exhibited lipid
      mixing with acceptor liposomes after elastase or proteinase K protease treatment.
      Activation of fusion, as monitored by a lipid mixing assay, appeared to be
      dependent on protease activity, as (1) heat inactivated enzyme did not activate
      liposomal fusion, and (2) the time and concentration dependence of proteinase K
      mediated cleavage of N-Ac-AA-DOPE correlated with membrane mixing. Liposomes
      could also be formulated that exhibited lipid mixing and transfer of aqueous
      fluorescent probe with erythrocyte ghosts. These observations demonstrate
      fusogenic lipids conjugated to enzyme substrates serve as triggerable fusion
      systems that may be useful for gene and drug delivery.

PMID- 9651470
TI  - Partial respecification of nasotemporal polarity in double-temporal chick and
      chimeric chick-quail eyes.
AB  - In chick embryos, naso-temporal polarity of the retina becomes established before
      Hamburger-Hamilton stage 10. To examine the plasticity of the early eye anlage,
      double-temporal eyes were made using stage 10-11 (E1.5) chick embryos and stage 8
      9 quail embryos. In vivo and in vitro experiments revealed that these double
      temporal compound eyes were not completely temporal but nasal in a large
      peripheral part of the graft. Four hours after transplantation, the nasal
      specific fork head transcription factor CBF1 was not expressed in double-temporal
      eyes but was clearly detectable 24 h later. This suggests that in the peripheral
      part of the graft, temporal positional values were changed into nasal positional
      values by a respecification process.

PMID- 9651471
TI  - A proton-translocating H+-ATPase is involved in C6 glial pH regulation.
AB  - Glial cells extrude acid equivalents to maintain pHi. Although four mechanisms
      have been described so far, pHi-control under physiological conditions is still
      not sufficiently explained. We therefore investigated whether a H+-translocating
      ATPase is involved in glial pHi homeostasis using an established glial cell line
      (C6 glioma). In the absence of bicarbonate, the inhibition of H+-ATPases by NEM
      led to a pHi decrease. The application of a more specific inhibitor (NBD-Cl)
      showed that the H+-ATPase involved is of the vacuolar type. Inhibition went along
      with delayed cell swelling. Together with the fact that glial acidification was
      far more pronounced in Na+-free media, this may serve as evidence for a secondary
      activation of Na+/H+-exchange once an activation setpoint is reached, which in
      turn causes secondary swelling from Na+-uptake. Stimulation of Na+/H+-exchange by
      PMA can increase the setpoint. pHi-recovery after an acid load was blocked by the
      inhibition of v-type H+-ATPase, if pHi did not reach 6.6 during the acid load.
      The inhibition of Na+/H+-exchange by amiloride inhibited recovery only if
      acidification was below the threshold. Finally, in bicarbonate-free media a v
      type H+-ATPase contributes to pH-regulation in glial cells, especially during pH
      homeostasis at physiological conditions, while Na+/H+-exchange gains significance
      during severe acid loads.

PMID- 9651472
TI  - Structural and functional analysis of the BMP-4 promoter in early embryos of
      Xenopus laevis.
AB  - The Xenopus laevis BMP-4 gene shows an evolutionary conserved structure
      containing two coding exons and a leader exon. The transcripts which are detected
      after zygotic activation of the gene in ventral mesoderm of late blastula stage
      embryos do either contain the leader exon or begin within the first intron.
      Luciferase reporter/promoter studies revealed multiple elements being required
      for the activation and for the spatial control of transcription. These elements
      are located within the upstream region and within the second intron and they
      interact with a most proximal located basal promoter being indispensable for
      transcriptional activation. The auto-activatory capacity of BMP-4 is mediated by
      several enhancer elements being responsive not only to BMP-4 but also to BMP-2
      signaling. BMP-2 might thus function as a natural activator of the BMP-4 gene in
      the early embryo. Since reporter activity obtained with distinct BMP-2/4
      responsive promoter deletion mutants is simultaneously inhibited by the dominant
      negative BMP receptor as well as by chordin, we suggest that down-regulation of
      the BMP-4 gene by chordin results from an interference with the auto-regulatory
      loop at the level of protein-protein interactions.

PMID- 9651473
TI  - Multiple Sp1 sites efficiently drive transcription of the TATA-less promoter of
      the human glypican 3 (GPC3) gene.
AB  - Simpson-Golabi-Behmel Syndrome (SGBS) is an X-linked disease characterized by pre
      and postnatal overgrowth. Recently, we have shown that mutations in the glypican
      family gene, GPC3, cause SGBS. This gene is predominantly expressed in the same
      mesoderm-derived tissues that overgrow in its absence. To investigate the basis
      for promoter function, 3.3kb of GC-rich DNA 5' of the transcribed region were
      fused to a luciferase cDNA, transfected into Caco-2 and NT2 cells, and assayed
      for activity. Deletion analysis identified a 218-bp fragment upstream of the
      transcription start site that conferred more than 80% of maximal reporter gene
      activation. This fragment contains five putative Sp1 binding sites, three of
      which (centered at nt -14, -34, and -92) were active when assessed by DNaseI
      footprinting and gel shift/supershift assays. Additionally, Sp1 specifically
      transactivated transcription in Sp1-deficient Drosophila SL2 cells, demonstrating
      the functionality of Sp1 on the GPC3 promoter. A full-length promoter construct
      was also highly active in HeLa cells, which do not express endogenous GPC3. These
      results indicate that the GPC3 promoter is dependent on Sp1 for proper
      activation, but tissue-specific repression in non-expressing cells must involve
      either DNA that lies outside the region tested or auxiliary structural features
      of chromatin.

PMID- 9651474
TI  - Modulatory drug action in an allosteric Markov model of ion channel behaviour:
      biphasic effects with access-limited binding to either a stimulatory or an
      inhibitory site.
AB  - Concentration-dependent biphasic effects of drugs on ion channel activity have
      been reported in a variety of preparations, usually with stimulatory effects seen
      at low concentrations followed by increasingly dominant inhibition at higher
      levels. Such behaviour is often interpreted as evidence for the existence of
      separate modulatory drug binding sites. We demonstrate in this paper that it is
      possible for biphasic effects to be produced in an allosteric model of a ligand
      activated ion channel, where diffusion-limited binding of the modulatory drug is
      restricted to either a stimulatory or an inhibitory site (but not both) because
      of steric overlap. The possibility of such an interaction mechanism should be
      kept in mind when interpreting experimental data if stoichiometric evidence from
      complementary techniques suggests that only one drug molecule is bound per
      receptor/ion channel complex.

PMID- 9651475
TI  - The loss of ventral ectoderm identity correlates with the inability to form an
      AER in the legless hindlimb bud.
AB  - We have characterized the early stages of murine hindlimb morphogenesis in the
      legless (lgl)mutant and non-mutant littermates. Initially the entire ventral
      ectoderm expresses many genetic markers characteristic of the AER (en-1, fgf-8,
      msx-2, dlx-2, cd44, and cx-43). Subsequently, the expression domain of most of
      these genes is restricted to the thickened ectoderm of the disto-ventral limb
      margin prior to forming an AER. In lgl, the expression of these genes is
      initiated but not maintained and the disto-ventral marginal ectoderm does not
      thicken. In contrast, Wnt7a expression is initiated and maintained in the dorsal
      ectoderm. The limb mesenchyme of lgl and non-mutant embryos initially expresses
      lmx-1b and fgf-10 uniformly. As the ventro-distal marginal ectoderm thickens, lmx
      1b is progressively dorsally restricted in non-mutants but continues to be
      expressed ventrally in lgl hindlimb buds. These data suggest that establishment
      of a dorso-ventral ectodermal interface is not sufficient for AER formation and
      that restriction of lmx-1b to the dorsal mesenchyme is coordinately linked to AER
      formation.

PMID- 9651476
TI  - Polymorphism in the 5' flanking region of the human somatostatin receptor subtype
      5.
AB  - The human somatostatin receptor subtype 5 (hSSTR5) gene has previously been
      cloned and localized to chromosome 16 p13.3. This region is evolutionarily
      conserved in all vertebrate genomes from the puffer fish (Fugu rubripes) to
      human, and also contains loci for genes associated with two common multisystemic
      disorders, adult polycystic kidney disease (PKD1) and tuberous sclerosis (TSC2).
      Analysis of the 5' flanking region of the hSSTR5 gene has revealed consensus
      sequences for a number of transcription factors as well as Alu-like repeat
      elements. In the present study, genomic DNA from 53 unrelated individuals was
      analysed by PCR and Southern blots probed with radiolabeled fragments generated
      from different segments of the hSSTR5 gene. We have identified two restriction
      fragment length polymorphisms (RFLP) with high heterozygosity values at the 5'
      flanking region of the hSSTR5 gene. These RFLP markers will be useful for
      determining the allelic loss of genetic material from this region. The observed
      polymorphism in the promoter region may affect the function of the hSSTR5 gene.

PMID- 9651477
TI  - Lipid interactions with human antiphospholipid antibody, beta 2-glycoprotein 1,
      and normal human IgG using the fluorescent probes NBD-PE and DPH.
AB  - Recurrent venous thrombosis, arterial thrombosis and pregnancy losses are
      clinical manifestation associated with antiphospholipid antibody (aPL) that
      recognizes negatively charged phospholipid antigens. Enzyme-linked immunosorbent
      assays (ELISA) are generally used to determine the presence and specificity of
      aPL. In this paper, a fluorescence spectroscopy method has been applied, through
      monitoring the alteration of fluorescence intensity and anisotropy of a
      fluorophore that was incorporated in liposomes to explore the changes of
      molecular structure or configuration elicited by the binding aPL with
      phospholipid antigens. The bilayer surface was markedly ordered by aPL binding as
      indicated by the surface-sensitive probe NBD-PE. The binding of aPL on the
      bilayer surface is saturable. The saturation concentration of aPL is 40% (w/w,
      aPL/lipid) for cardiolipin membranes. The binding of aPL on cardiolipin took
      place in the absence of beta 2-GP1. The addition of beta 2-GP1 further increased
      the anisotropy and decreased the intensity of fluorescence. The binding of aPL is
      predominantly attributed to electrostatic interaction, but the configuration of
      the acyl chains of phospholipid also plays a role. It is found that the thermal
      history is important for aPL binding. The incubation at 37 degrees C is more
      favorable for aPL binding than ambient temperature. Normal human serine (IgG-NHS)
      did not elicit any distinct change of NBD-PE fluorescence, which indicates it
      does not interact with the lipid.

PMID- 9651478
TI  - Identification of a short interspersed repetitive element in partially spliced
      transcripts of the bell pepper (Capsicum annuum) PAP gene: new evolutionary and
      regulatory aspects on plant tRNA-related SINEs.
AB  - In bell pepper, a gene encoding a major plastid-lipid associated protein is
      expressed as both partially and totally spliced transcripts (respectively PAP2
      and PAP1). Although PAP is present as a single-copy gene in the bell pepper
      genome, Southern blots using PAP2 as a probe revealed multiple homologous copies.
      Analyses of the intronic sequence of PAP2 showed the existence of a 206bp short
      interspersed repetitive element (SINE) belonging to the Ts family of
      retrotransposons (Yoshioka et al., 1993). Comparison with PAP sequences in other
      Solanaceae species suggested that the structure of the gene is highly conserved:
      the two introns are inserted at the same position. However, the Ts insertion
      found in bell pepper is absent in tobacco and tomato. Studies using RT-PCR showed
      that in these latter species only totally spliced transcripts of PAP are present.
      On the other hand, RNA analyses of tobacco plants transformed with the bell
      pepper PAP revealed the presence of both totally and incompletely spliced
      transcripts. Altogether our results support the hypothesis that the Ts insertion
      into the first intron of PAP results in a splicing defect of the corresponding
      pre-mRNA. Based on the presence of peculiar, previously unidentified Ts elements,
      a possible horizontal transmission of Ts elements from animals to plants is
      discussed.

PMID- 9651479
TI  - Linking cell-fate specification to planar polarity: determination of the R3/R4
      photoreceptors is a prerequisite for the interpretation of the Frizzled mediated
      polarity signal.
AB  - The adult eye of Drosophila is a highly ordered structure composed of about 800
      ommatidia, each displaying precise polarity. The planar polarity is reflected in
      the mirror-symmetric arrangement of ommatidia relative to the dorso-ventral
      midline, the equator. This arrangement is generated when ommatidia rotate towards
      the equator and the photoreceptor R3 displaces R4 creating different chiral forms
      in each half. Analysis of ommatidia mosaic for the tissue polarity gene frizzled
      (fz) has shown that the presence of a single Fz+ photoreceptor cell within the
      R3/ R4 pair is critical for the direction of rotation and chirality. By analysing
      clones mutant for seven-up (svp), in which R3/R4 precursors reside in their
      normal positions and become photoreceptor neurones but fail to adopt the normal
      R3/R4 fate, we find that the R3/R4 photoreceptor subtype specification is a
      prerequisite for planar polarisation in the eye. Moreover, in mosaic R3/R4 pairs
      we find that the svp- cell always adopts the R4 position. This bias is
      reminiscent of what happens in fz mosaic R3/R4 pairs, where the fz- cell also
      almost always adopts the R4 position. In addition, we find that in genotypes
      where too many cells adopt the R3/R4 fate, ommatidial polarity is also disturbed.
      Taken together, these data imply that correct specification of a single R3 cell
      per ommatidium is essential for the normal interpretation of the Fz-mediated
      polarity signal.

PMID- 9651480
TI  - Delivery of an anti-HIV-1 ribozyme into HIV-infected cells via cationic
      liposomes.
AB  - Cationic liposome-mediated intracellular delivery of a fluorescein-labeled
      chimeric DNA-RNA ribozyme targeted to the HIV-1 5' LTR was investigated, using
      THP-1, THP-1/HIV-1IIIB or HeLa/LAV cells. Different fluorescence patterns were
      observed when the cells were exposed to Lipofectamine, Lipofectin or DMRIE:DOPE
      (1:1) complexed to the ribozyme. With Lipofectamine intense cell-associated
      fluorescence was found. Incubation with Lipofectin resulted in less intense
      diffuse fluorescence, while with DMRIE an intense but sporadic fluorescence was
      observed. Differentiated THP-1/HIV-1IIIB cells were more susceptible to killing
      by liposome-ribozyme complexes than THP-1 cells. Under non-cytotoxic conditions
      (a 4-h treatment) complexes of 5, 10 or 15 microM Lipofectin or DOTAP:DOPE (1:1)
      and ribozyme, at lipid:ribozyme ratios of 8:1 or 4:1, did not affect p24
      production in THP-1/HIV-1IIIB cells in spite of the intracellular accumulation of
      the ribozyme. A 24-h exposure of THP-1/HIV-1IIIB cells to 5 microM Lipofectin or
      DOTAP:DOPE (1:1) complexed with either the functional or a modified control
      ribozyme reduced virus production by approximately 30%. Thus, the antiviral
      effect of the liposome-complexed ribozyme was not sequence-specific. In contrast,
      the free ribozyme at a relatively high concentration inhibited virus production
      by 30%, while the control ribozyme was ineffective, indicating a sequence
      specific effect. Both Lipofectin and DOTAP complexed with ribozyme were toxic at
      10 and 15 microM after a 24-h treatment. A 4-h treatment of HeLa/LAV cells with
      Lipofectin at 5, 10 or 15 microM was not toxic to the cells, but also did not
      inhibit p24 production. In contrast, treatment of HeLa CD4+ cells immediately
      after infection with HIV-1IIIB at the same lipid concentrations and
      lipid:ribozyme ratios was cytotoxic. Our results indicate that the delivery of
      functional ribozyme into cells by cationic liposomes is an inefficient process
      and needs extensive improvement before it can be used in ex vivo and in vivo
      applications.

PMID- 9651481
TI  - The origin and fate of pioneer myotomal cells in the avian embryo.
AB  - The ontogeny of the myotome was investigated using [3H]thymidine or Brdu
      treatment in conjunction with 1,1', di-octadecyl-3, 3, 3', 3',-tetramethylindo
      carbocyanine perchlorate (DiI) labeling and expression of specific markers. We
      have identified a subset of early post-mitotic cells that is present in the
      dorsomedial aspect of epithelial somites and is homogeneously distributed along
      their entire rostrocaudal extent. The post-mitotic quality of this cell subset
      enabled us to trace their fate in time-course experiments. Following initial
      somite dissociation, this epithelial post-mitotic layer bends underneath the
      medial portion of the nascent dermomyotome. Then, these cells progressively lose
      epithelial arrangement and migrate in a rostral direction where they accumulate
      temporarily. Subsequently, these early post-mitotic precursors extend processes
      that reach both rostral and caudal edges of each segment. Medial somite-derived
      myofibers also fill the entire mediolateral extent of the segment and reach the
      dorsomedial lip of the dermomyotome, thus forming the primary myotome. During
      this process, their large nuclei localize to a narrow stripe in the middle of the
      nascent myotome. Consistent with the proliferation studies, DiI labeling of the
      medial epithelial somite cells gave rise to a primary myotomal structure, and
      continuous pulsing of the DiI-injected embryos with radioactive thymidine
      revealed that these fibers indeed developed from post-mitotic progenitors. As
      these early post-mitotic cells that arise prior to somite dissociation are the
      first wave of progenitors that constitutes the myotome, we have termed them avian
      muscle pioneers. We propose that the primary myotome formed by the muscle
      pioneers constitutes a longitudinal scaffold that serves as a substrate for the
      addition of subsequent waves of myotomal cells.

PMID- 9651482
TI  - The four cdc25 genes from the nematode Caenorhabditis elegans.
AB  - During eukaryotic evolution, multicellular organisms have evolved multiple
      members of gene families that may display unique, partially overlapping, or
      redundant functions during development. More than 75% of the C. elegans genome
      has been sequenced, which represents approximately 95% of the coding sequences.
      This provides a unique opportunity to identify most, if not all, of the members
      of a given gene family. We have searched the C. elegans genome database for
      members of a key family of cell cycle regulators, the CDC25 phosphatases, and
      have identified four genes. The four C. elegans genes represent a larger family
      within a single organism than has been reported so far in Drosophila, mice and
      humans. An amino acid comparison revealed a high degree of similarity and
      identity within the phosphatase domain. This analysis also identified an expanded
      consensus sequence that can be used to discover new members of the CDC25
      phosphatase family. However, the four C. elegans sequences display a few novel
      amino acid substitutions in the residues surrounding the invariant catalytic
      motif CX5R. These data demonstrate the value of genome database searching for
      identifying new members of known gene families, understanding genetic diversity,
      and for studying gene structure.

PMID- 9651483
TI  - Cloning and structure of a rabbit protein inhibitor of neuronal nitric oxide
      synthase (PIN) gene and its pseudogene.
AB  - Neuronal nitric oxide synthase (nNOS), the biosynthetic enzyme for the free
      radical neurotransmitter nitric oxide, was found to be inhibited by the protein
      inhibitor of nNOS, designated PIN (Jaffrey, S.R. and Snyder, S.H., (1996) Science
      274, 774-777). The cDNA clone encoding a rabbit PIN was isolated, and the
      translated PIN protein was89 amino acid long sharing 100% of its deduced amino
      acid sequence with rat PIN. Using a radiolabelled riboprobe derived from the
      rabbit PIN cDNA, the rabbit PIN gene was isolated from a rabbit genomic library
      and the structural organization of the gene was determined. The gene contains
      three exons separated by two introns spanning approx. 2.3kb of genomic DNA. 5'
      RACE analysis mapped the transcriptional initiation site 98bp upstream of the
      initiator methionine codon. Characterization of the 5' flanking genomic region
      revealed that the rabbit PIN promoter is TATA-less, but contains a CCAAT box as
      well as various putative transcription factor-binding elements. The 3'
      untranslated region contains consensus polyadenylation signal (AATAAA). We also
      isolated an intronless gene with 93% nucleotide sequence similarity to the rabbit
      PIN cDNA. Sequence analysis indicates that the open reading frame was interrupted
      by a premature stop codon and frameshift which resulted in a processed pseudogene
      of the rabbit PIN.

PMID- 9651484
TI  - Organization of the canine gene encoding the E isoform of retinal guanylate
      cyclase (cGC-E) and exclusion of its involvement in the inherited retinal
      dystrophy of the Swedish Briard and Briard-beagle dogs.
AB  - Intracellular cyclic GMP concentration is known to change in response to a wide
      variety of agents, including hormones, neurotransmitters or light. In vertebrate
      photoreceptors, different membrane-bound guanylate cyclase isoforms are
      responsible for cGMP synthesis and thus directly involved in termination of light
      signalling via the phototransduction cascade and recovery of the dark state. We
      have characterized a 4.7 kb long cDNA for the canine retinal guanylate cyclase
      isoform E (cGC-E) predicting a polypeptide of 1109 amino acids. The genomic
      structure and the complete sequence of the canine GC-E gene, which consists of 20
      exons and spans about 14.5 kb, has also been determined. Northern blot analysis
      showed that GC-E was expressed in the canine retina as a 4.7 and 6.1 kb large
      transcript. RT-PCR analysis also detected low expression in cerebrum (occipital
      lobe). We performed a sequence analysis of the cGC-E gene in animals of a Swedish
      Briard and Briard-Beagle dog kinship in which an inherited retinal dystrophy is
      segregating. Several intragenic DNA polymorphisms were identified and used for
      segregation analysis which excluded cGC-E as a candidate gene for this type of
      canine retinal dystrophy.

PMID- 9651485
TI  - Ventral mesoderm induction and patterning by bone morphogenetic protein
      heterodimers in Xenopus embryos.
AB  - Bone morphogenetic proteins (BMPs) perform diverse functions in vertebrate
      development. Here we demonstrate that the heterodimeric BMP-4/7 protein directly
      induces ventral mesoderm and blood in Xenopus animal caps, and BMP-2/7
      heterodimers may function similarly. We also provide indirect evidence that BMP
      heterodimers function in embryos, using assays with dominant-negative BMP
      ligands. Homodimeric BMP-2 and BMP-4 proteins do not induce mesoderm, but they
      ventralize mesoderm induction by activin. In contrast, BMP-7 protein interferes
      with mesoderm induction by activin, but BMP-7 stimulates ventral mesoderm
      induction by the heterodimer, BMP-4/7. This novel property of BMP-7 distinguishes
      it from other BMPs. BMP-7 may therefore function in early embryogenesis to
      antagonize activin signals and potentiate BMP signals. We propose that BMP
      heterodimers convey signals for ventral mesoderm induction and patterning in
      Xenopus development.

PMID- 9651486
TI  - Identification and functional analysis of the mouse lens filensin gene promoter.
AB  - Filensin (also called CP94; CP95; CP97; 115kDa protein) is a component of the
      lens-specific beaded filament which is believed to be functionally important in
      lens fiber cell differentiation and in maintaining lens fiber cell conformation
      and transparency. A 17.2kb fragment containing the 5'-upstream sequence of the
      filensin gene was isolated. S1-mapping analysis determined the transcription
      start point (tsp; +1) which locates at 94base pairs upstream from the initiating
      ATG on the filensin gene. In addition to a major tsp, a minor tsp (-136) was
      observed. DNA sequence of the fragment around the tsp (-2144 to +155) was
      identified. Analysis of the DNA sequence of the promoter region around tsp
      revealed two motifs with sequence homology to Sox2 and Maf recognition sequences
      in addition to one GATA-1 site, two Sp1 binding sites, and three AP-2 binding
      motifs. No TATA-box or CCAAT-motif was found around the tsp region. A series of
      sequentially deleted fragments of (-2144 to +40) were fused to firefly luciferase
      reporter plasmid pGL2 and tested for activity in chicken embryonic lens explants.
      A minimal promoter region for mouse filensin of (-70 to +40) was identified. The
      lens-specific promoter activity was detected using lens explants cultured within
      12h after dissection. The activity was remarkably enhanced by culture in the
      presence of 5ng/ml of basic fibroblast growth factor. Each one of the Sp1 and AP
      2 binding motifs was localized to the fragment of (-27 to +40) using
      electrophoretic mobility shift assays. These are the first data to identify the
      basic elements to the 5'-upstream sequences of the filensin gene, namely the tsp
      and the minimal filensin promoter.

PMID- 9651487
TI  - Membrane permeabilisation and antimycoplasmic activity of the 18-residue
      peptaibols, trichorzins PA.
AB  - The membrane permeabilisation properties of six linear natural 18-residue
      peptaibols, termed trichorzins PA, have been assessed on liposomes and on
      mollicutes (trivial name, mycoplasmas), a class of parasitic bacteria
      characterized by a small genome, the lack of a cell wall, a minute cell size, and
      the incorporation in their plasma membrane of exogenously supplied cholesterol.
      The trichorzins PA used in this study (PA II, PA IV-VI, PA VIII, and PA IX)
      differ between them by amino acid or amino alcohol substitutions at positions 4,
      7, and 18, and form slightly amphipathic alpha-helices. They proved bactericidal
      for mollicutes belonging to the genera Acholeplasma, Mycoplasma, and Spiroplasma,
      with minimal inhibitory concentrations (3.12</=MICs</=50 microM) generally 2 to 4
      fold higher than those of alamethicin F50, a related 20-residue peptide
      (1.56</=MICs</=12.5 microM). Spiroplasma cells were apparently not protected by
      the presence of spiralin on their surface. The activities of the six trichorzins
      PA were not influenced by their sequence variations and no synergistic effect was
      observed. Consistent with the marginal effect of cholesterol on the incorporation
      of the trichorzins PA into liposome bilayers, the antibiotic activity was
      independent of the amount of cholesterol in the membranes of the different
      mollicutes. The trichorzins PA and alamethicin inhibited the motility of
      Spiroplasma melliferum, the helical cells being deformed and split into coccoid
      forms. Membrane potential measurements in Acholeplasma laidlawii and S.
      melliferum showed that trichorzin PA V and alamethicin F50 very efficiently
      depolarized the plasma membrane of mollicutes. This was consistent with
      fluorescence and 23Na NMR measurements on liposomes that revealed the
      permeabilisation of the lipid bilayer and the nonselective ionophoric activity of
      the trichorzins PA. These data suggest that the bactericidal activity exhibited
      by the trichorzins PA on mollicutes is due to the permeabilisation of the plasma
      membrane.

PMID- 9651488
TI  - Emotion in the perspective of an integrated nervous system.

PMID- 9651489
TI  - Structural divisions and functional fields in the human cerebral cortex.
AB  - The question of what is a cortical area needs a thorough definition of borders
      both in the microstructural and the functional domains. Microstructural
      parcellation of the human cerebral cortex should be made on multiple criteria
      based on quantitative measurements of microstructural variables, such as neuron
      densities, neurotransmitter receptor densities, enzyme densities, etc. Because of
      the inter-individual variations of extent and topography of microstructurally
      defined areas, the final microstructurally defined areas appear as population
      maps. In the functional domain, columns, patches and blobs signifying
      synaptically active parts of the cortex appear as cortical functional fields.
      These fields are the largest functional entities of the cerebral cortex according
      to the cortical field hypothesis. In its strong version, the cortical field
      hypothesis postulates that all neurons and synapses within the fields perform a
      co-operative computation. A number of such fields together provide the functional
      contribution of the cerebral cortex. The functional parcellation of the human
      cerebral cortex must be based on field population maps, which after intersection
      analysis appear as functional domains. The major structural-functional hypothesis
      to be examined is whether these functional domains are equi-territorial to the
      microstructurally defined meta-maps. The cortical hypothesis predicts that, if
      two brain tasks make use of one or several identical or largely overlapping
      fields, they cannot be performed simultaneously without errors or increases in
      latency. Evidence for such interference is presented. This evidence represents a
      restriction in the parallel processing of the human brain. In the posterior part
      of the brain not only visual cortical areas may qualify for parallel processing,
      but also the somatosensory cortices appear to have separate functional streams
      for the detection of microgeometry and macrogeometry.

PMID- 9651490
TI  - Comparison of sequence and function of the Oct-6 genes in zebrafish, chicken and
      mouse.
AB  - To examine the role of the Oct-6 gene in Schwann cell differentiation we have
      cloned and characterized the chicken and zebrafish homologues of the mouse Oct-6
      gene. While highly homologous in the Pit1-Oct1/2-Unc86 (POU) domain, sequence
      similarities are limited outside this domain. Both genes are intronless and both
      proteins lack the amino acid repeats that are a characteristic feature of the
      mammalian Oct-6 proteins. However as in mammals, the aminoterminal parts of the
      chicken and zebrafish Oct-6 proteins are essential for transactivation of octamer
      containing promoters. By immunohistochemistry we have found that the chicken Oct
      6 protein is expressed in late embryonic ensheathing Schwann cells of the sciatic
      nerve and is rapidly downregulated when myelination proceeds. This expression
      profile in glial cells is identical to that in the mouse and rat. Furthermore the
      zebrafish Oct-6 homolog is expressed in the posterior lateral nerve at a time
      when it contains actively myelinating Schwann cells. Thus despite extensive
      primary sequence divergence among the vertebrate Oct-6 proteins, the expression
      of the chicken and zebrafish Oct-6 proteins is consistent with the notion that
      Oct-6 functions as a 'competence factor' in promyelin cells to execute the
      myelination program.

PMID- 9651491
TI  - Evidence for a role of the multidrug resistance protein (MRP) in the outward
      translocation of NBD-phospholipids in the erythrocyte membrane.
AB  - Phosphatidylserine (PS) containing a 7-nitrobenz-2-oxa-1, 3-diazol-4-yl- (NBD-)
      hexanoyl residue, like native PS, preferentially distributes into the inner
      membrane leaflet of human erythrocytes. In the case of NBD-PS, this preference
      results from two opposite active processes, an inward translocation mediated by
      the aminophospholipid flippase and an outward translocation mediated by an ill
      defined floppase. Selective inhibition of this floppase by alkylating reagents or
      cationic and anionic drugs increases the extent of accumulation of NBD-PS in the
      inner membrane leaflet from about 70% in control cells to about 90%. Different
      inhibitor sensitivities of the flippase and the floppase strongly suggest that
      both represent different entities. The floppase was characterized in further
      detail by comparing inhibitory effects of various compounds on this translocase
      with their effects on known primary active transport systems for amphiphilic
      compounds. The inhibitory effects of various drugs, glutathione conjugates and
      GSSG on the floppase activity closely correlate with those reported for the
      active transport by the multidrug resistance protein (MRP) while only poorly
      going parallel with those for the active transport by the low affinity pump for
      glutathione conjugates and the multidrug resistance MDR1 P-glycoprotein. The NBD
      phospholipid floppase activity of the erythrocyte is thus probably a function of
      MRP.

PMID- 9651492
TI  - Characterization and targeted disruption of a glycosyltransferase gene in the
      tylosin producer, Streptomyces fradiae.
AB  - An open reading frame, designated tylN, has been identified by sequence analysis
      at one end of the tylosin biosynthetic gene cluster of Streptomyces fradiae,
      alongside a cluster of genes encoding the biosynthesis of dTDP-deoxyallose. This
      6-deoxyhexose sugar is converted to mycinose, via bis O-methylation, following
      attachment to the polyketide lactone during tylosin biosynthesis. The deduced
      product of tylN is similar to several glycosyltransferases, authentic and
      putative, and displays a consensus sequence motif that appears to be
      characteristic of a sub-group of such enzymes. Specific disruption of tylN within
      the S. fradiae genome resulted in the production of demycinosyl-tylosin, whereas
      other glycosyltransferase activities involved in tylosin biosynthesis were not
      affected. Evidently, tylN encodes deoxyallosyl transferase.

PMID- 9651493
TI  - Homeotic regulation of segment-specific differences in neuroblast numbers and
      proliferation in the Drosophila central nervous system.
AB  - The number and pattern of neuroblasts that initially segregate from the
      neuroectoderm in the early Drosophila embryo is identical in thoracic and
      abdominal segments. However, during late embryogenesis differences in the numbers
      of neuroblasts and in the extent of neuroblast proliferation arise between these
      regions. We show that the homeotic genes Ultrabithorax and abdominal-A regulate
      these late differences, and that misexpression of either gene in thoracic
      neuroblasts after segregation is sufficient to induce abdominal behaviour.
      However, in wild type embryos we only detect abdominal-A and Ultrabithorax
      proteins in early neuroblasts. Furthermore, transplantation experiments reveal
      that segment-specific behaviour is determined prior to neuroblast segregation.
      Thus, the segment-specific differences in neuroblast behaviour seem to be
      determined in the early embryo, mediated through the expression of homeotic genes
      in early neuroblasts, and executed in later programmes controlling neuroblast
      numbers and proliferation.

PMID- 9651494
TI  - Mosaic structure of the cox2 gene in the petite negative yeast
      Schizosaccharomyces pombe: a group II intron is inserted at the same location as
      the otherwise unrelated group II introns in the mitochondria of higher plants.
AB  - In contrast to homologous genes in other fungal mitochondrial genomes, the gene
      encoding subunit 2 of cytochrome oxidase (cox2) in several Schizosaccharomyces
      pombe strains contains a large group II intron. Its 2436 nucleotides can be
      folded into a typical group II intron secondary structure, possessing all the
      expected sequence motifs for subgroup IIA1 (Michel et al., 1989). This intron is
      remarkable for the following reasons: (i) Five nucleotide changes were observed
      compared with the continuous form of the cox2 gene in the reference strain 50 at
      the 3'-exon sequence, but not in the 5'-exon. (ii) One of these changes occurred
      at the splice point leading to a serine instead of a threonine residue in the
      deduced cox2 polypeptide. In all cases, the alterations resulted in the
      replacement of more frequently used codons by rare ones. (iii) Although the
      intron is able to undergo splicing, the sequence motifs thought to be necessary
      for interaction between the 5'-exon and the intron during the splicing process
      (the EBS1/IBS1 as well as the EBS2/IBS2 pairings) are unusual. (iv) The intron is
      inserted at the same location in the cox2 gene as the otherwise unrelated intron
      from higher plants.

PMID- 9651495
TI  - Enhanced efficiency of a targeted fusogenic peptide.
AB  - Membrane targeting was investigated as a potential strategy to increase the
      fusogenic activity of an isolated fusion peptide. This was achieved by coupling
      the fusogenic carboxy-terminal part of the beta-amyloid peptide (Abeta, amino
      acids 29-40), involved in Alzheimer's disease, to a positively charged peptide
      (PIP2-binding peptide, PBP) interacting specifically with a naturally occurring
      negatively charged phospholipid, phosphatidylinositol 4, 5-bisphosphate (PIP2).
      Peptide-induced vesicle fusion was spectroscopically evidenced by: (i) mixing of
      membrane lipids, (ii) mixing of aqueous vesicular contents, and (iii) an
      irreversible increase in vesicle size, at concentrations five to six times lower
      than the Abeta(29-40) peptide. In contrast, at these concentrations the PBP
      Abeta(29-40) peptide did not display any significant activity on neutral
      vesicles, indicating that negatively charged phospholipids included as targets in
      the membranes, are required to compensate for the lower hydrophobicity of this
      peptide. When the alpha-helical structure of the chimeric peptide was induced by
      dissolving it in trifluoroethanol, an increase of the fusogenic potential of the
      peptide was observed, supporting the hypothesis that the alpha-helical
      conformation of the peptide is crucial to trigger the lipid-peptide interaction.
      The specificity of the interaction between PIP2 and the PBP moiety, was shown by
      the less efficient targeting of the chimeric peptide to membranes charged with
      phosphatidylserine. These data thus demonstrate that the specific properties of
      both the Abeta(29-40) and the PBP peptide are conserved in the chimeric peptide,
      and that a synergetic effect is reached through chemical linkage of these two
      fragments.

PMID- 9651496
TI  - Functional magnetic resonance imaging of mental rotation and memory scanning: a
      multidimensional scaling analysis of brain activation patterns.

PMID- 9651497
TI  - An internet-accessible database of mouse developmental anatomy based on a
      systematic nomenclature.
AB  - This paper reports an internet-accessible database of mouse developmental anatomy
      (DMDA) that currently holds a hierarchy of the names and synonyms of the tissues
      in the first 22 Theiler stages of development (E1-E13.5), together with other
      appropriate information. The purposes of the database are to provide, first, a
      nomenclature for analyzing normal and mutant mouse anatomy, and second a language
      for inputting, storing and querying gene-expression and other spatially organized
      data. DMDA currently contains some 6900 named and staged tissues (e.g. 360 and
      1161 tissues in Theiler stage (TS) 14 (E9) and TS22 (E13.5) embryos). DMDA will
      be extended to include further lineage and other data when it becomes available.
      The database can be interactively accessed over the internet using either a Java
      or a non-Java WWW browser at http://genex.hgu.mrc.ac.uk/.

PMID- 9651498
TI  - Salient features of synaptic organisation in the cerebral cortex.
AB  - The neuronal and synaptic organisation of the cerebral cortex appears exceedingly
      complex, and the definition of a basic cortical circuit in terms of defined
      classes of cells and connections is necessary to facilitate progress of its
      analysis. During the last two decades quantitative studies of the synaptic
      connectivity of identified cortical neurones and their molecular dissection
      revealed a number of general rules that apply to all areas of cortex. In this
      review, first the precise location of postsynaptic GABA and glutamate receptors
      is examined at cortical synapses, in order to define the site of synaptic
      interactions. It is argued that, due to the exclusion of G protein-coupled
      receptors from the postsynaptic density, the presence of extrasynaptic receptors
      and the molecular compartmentalisation of the postsynaptic membrane, the synapse
      should include membrane areas beyond the membrane specialisation. Subsequently,
      the following organisational principles are examined: 1. The cerebral cortex
      consists of: (i) a large population of principal neurones reciprocally connected
      to the thalamus and to each other via axon collaterals releasing excitatory amino
      acids, and, (ii) a smaller population of mainly local circuit GABAergic neurones.
      2. Differential reciprocal connections are also formed amongst GABAergic
      neurones. 3. All extrinsic and intracortical glutamatergic pathways terminate on
      both the principal and the GABAergic neurones, differentially weighted according
      to the pathway. 4. Synapses of multiple sets of glutamatergic and GABAergic
      afferents subdivide the surface of cortical neurones and are often co-aligned on
      the dendritic domain. 5. A unique feature of the cortex is the GABAergic axo
      axonic cell, influencing principal cells through GABAA receptors at synapses
      located exclusively on the axon initial segment. The analysis of these salient
      features of connectivity has revealed a remarkably selective array of
      connections, yet a highly adaptable design of the basic circuit emerges when
      comparisons are made between cortical areas or layers. The basic circuit is most
      obvious in the hippocampus where a relatively homogeneous set of spatially
      aligned principal cells allows an easy visualization of the organisational rules.
      Those principles which have been examined in the isocortex proved to be identical
      or very similar. In the isocortex, the basic circuit, scaled to specific
      requirements, is repeated in each layer. As multiple sets of output neurones
      evolved, requiring subtly different needs for their inputs, the basic circuit may
      be superimposed several times in the same layer. Tangential intralaminar
      connections in both the hippocampus and isocortex also connect output neurones
      with similar properties, as best seen in the patchy connections in the isocortex.
      The additional radial superposition of several laminae of distinct sets of output
      neurones, each representing and supported by its basic circuit, requires a co
      ordination of their activity that is mediated by highly selective interlaminar
      connections, involving both the GABAergic and the excitatory amino acid releasing
      neurones. The remarkable specificity in the geometry of cells and the selectivity
      in placement of neurotransmitter receptors and synapses on their surface,
      strongly suggest a predominant role for time in the coding of information, but
      this does not exclude an important role also for the rate of action potential
      discharge in cortical representation of information.

PMID- 9651499
TI  - Differential activation of system A and betaine/GABA transport in MDCK cell
      membranes by hypertonic stress.
AB  - Accumulation of osmolytes by renal cells is due in part to increased uptake via
      specific transporters. These include amino acid transport system A and the
      betaine/GABA transporter (BGT1). Transport changes have been characterized using
      intact cells which makes the intracellular mechanisms difficult to determine. In
      this study the hypertonic upregulation of system A and BGT1 was studied directly
      at the membrane level in Madin-Darby canine kidney (MDCK) cells. Both system A
      and BGT1 transport systems were detected in an isolated membrane fraction
      containing plasma membranes. System A transport was increased in membranes
      prepared from cells after 6 h hypertonic stress (449 mosmol/kg) but BGT1 activity
      was minimal and not different from isotonic controls. The increase in system A
      was blocked by inhibitors of RNA and protein synthesis. BGT1 transport was
      induced in membranes prepared after 24 h hypertonicity. At this time system A
      activity in the membrane fraction remained increased, unlike the downregulation
      observed in intact MDCK cells. We conclude that differential upregulation of
      system A and BGT1 by hypertonic stress is due to intrinsic changes in these
      transporters at the membrane level. In contrast, the downregulation of system A
      in intact cells when hypertonicity is prolonged for 24 h is likely due to the
      action of an intracellular repressor that is not present in the isolated
      membranes.

PMID- 9651500
TI  - Three alternatively spliced mouse slow skeletal muscle troponin T isoforms:
      conserved primary structure and regulated expression during postnatal
      development.
AB  - We have cloned and sequenced full-length cDNAs encoding mouse slow skeletal
      muscle troponin T (sTnT). Alternative mRNA splicing-generated two high Mr
      isoforms and one low Mr sTnT isoform differing in the NH2-terminal primary
      structure have been identified by Western blotting, reverse transcription
      polymerase chain reaction and cDNA cloning/expression analyses. Together with a
      5'-alternative exon that was also found in human sTnT encoding an 11-amino-acid
      acidic segment, the results revealed a novel alternative splicing pathway to
      include or exclude a three-base segment to generate additional sTnT isoforms with
      NH2-terminal charge variations. Overriding the phylogenetic divergence, primary
      structure of sTnT is better conserved between mammalian and avian species than
      that of cardiac, fast and skeletal muscle TnTs from one species. Western blots
      demonstrate four expression patterns of sTnT during postnatal skeletal muscle
      development: (1) a decrease to a non-detectable level in mouse masseter, (2) an
      increase to become the sole TnT in sheep masseter, (3) an increase of the total
      level as well as the proportion of the low Mr isoform in sheep diaphragm and, (4)
      no significant change in total level or high/low Mr isoform ratio in sheep
      gastrocnemius. The highly conserved primary structure and fiber type-specific and
      developmentally regulated expression of sTnT indicate a physiological importance
      of this under-studied member of the TnT gene family.

PMID- 9651501
TI  - Mammalian and Drosophila dachshund genes are related to the Ski proto-oncogene
      and are expressed in eye and limb.
AB  - We have isolated mammalian homologues of the Drosophila dachshund gene. Two
      domains of high conservation, one of which contains an alpha-helical, coiled-coil
      motif, show similarity to the Ski family of genes. We therefore propose that
      Dachshund belongs to a superfamily including these genes. Mouse Dachshund (Dach)
      is expressed in the eye and limb, structures affected by the Drosophila loss-of
      function mutant, and rib primordia, CNS and genital eminence. Pax6 and Dach show
      overlapping but non-identical expression patterns. Dach expression is unaffected
      in smalleye mouse brain, indicating that Pax6 is not directly activating Dach. In
      Drosophila eye development dachshund is a component of an interacting network of
      proteins. Genes homologous to many of these exist in mammals; Dach joins this
      expanding group.

PMID- 9651502
TI  - Interaction of DPPC monolayers with soluble surfactants: electrostatic effects of
      membrane perturbants.
AB  - We studied the effects of four soluble surfactants on DPPC monolayers to
      elucidate the action of these membrane perturbants. The presence of nonionic N-9
      and amphoteric C31G strongly affected the pure DPPC isotherm, while anionic SDS
      and cationic DTAB had little effect. The impact of surfactant on DPPC domain
      shape in the liquid condensed-liquid expanded coexistence region showed the
      opposite result. Neutral surfactants had minimal effect on the shape of DPPC
      domains; charged surfactants, on the other hand, induced a new shape transition
      at high surface pressures previously unreported for DPPC domains. All of these
      results are discussed with particular attention given to electrostatic effects at
      the interface.

PMID- 9651503
TI  - Identification of a novel casein kinase-1 homolog in fission yeast
      Schizosaccharomyces pombe.
AB  - Fission yeast cells lacking either the ste9+- or rum1+ function cannot enter the
      cell differentiation pathway upon nutritional starvation. Sterility in both
      mutants is suppressed by the srs1-S41 mutation. A gene encoding a novel casein
      kinase-1 (CK1) isoform, cki3+, was isolated as a high-copy-number suppressor gene
      of the srs1 mutation. Cki3 protein is structurally more related to the Cki/Yck
      subfamily proteins than those of the Hhp/Hrr25 subfamily. A mutant cki3 gene in
      which a highly conserved lysine residue in the kinase subdomain II was
      substituted to arginine lost the ability to recover the growth defect in the srs1
      mutant, indicating that catalytic activity was necessary for suppression. Gene
      disruption revealed that cki3+ was dispensable for cell viability, and cells
      lacking functional cki3+ exhibited no characteristic phenotype. Thus, S. pombe
      has three highly related CK1 isoforms (Cki1, Cki2 and Cki3), but none of them has
      an essential function.

PMID- 9651504
TI  - The Xcad-2 gene can provide a ventral signal independent of BMP-4.
AB  - Patterning of the marginal zone in the Xenopus embryo has been attributed to
      interactions between dorsal genes expressed in the organizer and ventral-specific
      genes. In this antagonistic interplay of activities, BMP-4, a gene that is not
      expressed in the organizer, provides a strong ventralizing signal. The Xenopus
      caudal type homeobox gene, Xcad-2, which is expressed around the blastopore with
      a gap over the dorsal lip, was analyzed as part of the ventral signal. Xcad-2 was
      shown to efficiently repress during early gastrula stages the dorsal genes gsc,
      Xnot-2, Otx-2, XFKH1 and Xlim-1, while it positively regulates the ventral genes,
      Xvent-1 and Xvent-2, with Xpo exhibiting a strong positive response to Xcad-2
      overexpression. Xcad-2 was also capable of inducing BMP-4 expression in the
      organizer region. Support for a ventralizing role for Xcad-2 was obtained from co
      injection experiments with the dominant negative BMP receptor which was used to
      block BMP-4 signaling. Under lack-of-BMP-signaling conditions Xcad-2 could still
      regulate dorsal and ventral gene expression and restore normal development,
      suggesting that it can act downstream of BMP-4 signaling or independently of it.
      Xcad-2 could also inhibit secondary axis formation and dorsalization induced by
      the dominant negative BMP receptor. Xcad-2 was also shown to efficiently reverse
      the dorsalizing effects of LiCl. These results place Xcad-2 as part of the
      ventralizing gene program which acts during early gastrula stages and can execute
      its ventralizing function in the absence of BMP signaling.

PMID- 9651505
TI  - In vitro reconstitution of stratum corneum lipid lamellae.
AB  - In the final stages of differentiation in the epidermis of terrestrial mammals,
      lipids are extruded into the intercellular spaces. The initially extruded lipid
      becomes transformed into broad, multilamellar sheets that are found in the
      intercellular spaces throughout the stratum corneum. These lamellae display an
      unusual alternating broad-narrow-broad pattern of lucent bands as revealed by
      transmission electron microscopy (TEM). This arrangement results in two
      periodicities that can be measured from electron micrographs and are also evident
      in X-ray diffraction-5 nm (broad) and 13 nm (broad-narrow-broad). The goal of the
      present study was to reconstitute these lamellae in vitro. Porcine stratum
      corneum lipids were applied to Millipore filters. The disks were placed in water
      and heated to 80 degrees C for 1 h. After cooling, the disks were stored over
      desiccant. At each stage, the disks were prepared for TEM. TEM revealed that the
      application of the lipid solutions onto the disks resulted to deposition of
      mostly amorphous material. Heating in water resulted in the formation of many
      lamellae. The width of the lamellae was uniform and in the range of 5 to 6 nm
      with no broad-narrow-broad pattern; however, after storage under desiccating
      conditions, the broad-narrow-broad pattern was reproduced.

PMID- 9651506
TI  - The emergence of the volume transmission concept.
AB  - Interneuronal communication in the central nervous system (CNS) have always been
      of basic importance for theories on the cerebral morphofunctional architecture.
      Our group has proposed that intercellular communication in the brain can be
      grouped into 2 broad classes based on some general features of the transmission:
      wiring (WT) and volume (VT) transmission. WT occurs via a relatively constrained
      cellular chain (wire), while VT consists of 3-dimensional diffusion of signals in
      the extracellular fluid (ECF) for distances larger than the synaptic cleft. Both
      morphological and functional evidence indicates that dopamine (DA) synapses in
      striatum are 'open' synapses, i.e., synapses which favor diffusion of the
      transmitter into the surrounding ECF and observations are compatible with the
      view that DA varicosities can synthesize, store and release DA for VT. The
      DAergic mesostriatal transmission has, therefore, been examined by several groups
      to give experimental support to VT. Moreover, due to its minor structural
      requirements, VT may become prevalent under some pathological conditions, e. g.
      Parkinson's disease. In animal models of DAergic pathway degeneration, it has
      been shown that a compensatory activation of surviving DA terminals may lead to a
      preferential potentiation of VT. WT and VT favor different and complementary
      types of computation. VT is markedly slower and less safe than WT, but has minor
      spatial constraints and allows the reach of a large number of targets. Models of
      neuronal systems integrating classical neuronal circuits and diffusible signals
      begin to show how WT and VT may interact in the neural tissue.

PMID- 9651507
TI  - Novel testis-specific protein that interacts with heat shock factor 2.
AB  - Although heat shock factor 2 (HSF2) binds to heat shock element (HSE)
      constitutively during differentiation, development and spermatogenesis, little is
      known about the nature and mechanism of transcriptional control of heat shock
      genes by HSF2. We screened a human testis cDNA library for proteins that can
      associate with HSF2 by the yeast two-hybrid system, and isolated clones encoding
      a novel protein, designated HSF2 binding protein (HSF2BP), that associates with
      HSF2 in vitro and in vivo and is specifically expressed in testis. The
      interaction seemed to occur between the trimerization domain of HSF2 and the
      amino terminal hydrophilic region of HSF2BP that comprises two leucine zipper
      motifs. HSF2BP may therefore be involved in modulating HSF2 activation in testis.

PMID- 9651508
TI  - Free liposomes enhance the transfection activity of DNA/lipid complexes in vivo
      by intravenous administration.
AB  - Factors that regulate the transfection efficiency of cationic lipid-based
      carriers are still largely unknown. We have shown in a previous report [F. Liu,
      H.W. Qi, L. Huang, D. Liu, Factors controlling the efficiency of cationic lipid
      mediated transfection in vivo via intravenous administration, Gene Ther., 4
      (1997) 517-523. ] that the transfection efficiency, to the lung, of a lipid
      formulation composed of N-[1-(2,3-dioleoyloxy)propyl-N,N, N-trimethylammonium
      chloride (DOTMA) and Tween 80 is directly proportional to the ratio of DOTMA to
      DNA. In this study, we investigated the mechanism underlying the high cationic
      lipid to DNA ratio dependent transfection activity. Specifically, we have
      examined the role of free cationic liposomes in affecting the transfection
      efficiency of the DNA/lipid complexes in vivo by intravenous administration. The
      data show that greater transfection activity of DNA/lipid complexes in the lung
      at a higher cationic lipid to DNA ratio is due to the function of free liposomes
      present in the DNA/lipid mixture. Free liposomes enhance the transfection
      activity of DNA/lipid complexes by increasing the retention time of DNA and
      decreasing transgene degradation in different organs. In addition to DOTMA
      liposomes, liposomes composed of 1,2-dioleoyl-3-trimethylammonium propane
      chloride (DOTAP) and 3beta[N-(N', N'-dimethylaminoethane) carbamoyl] cholesterol
      (DC-Chol) also enhance the level of gene expression in animals transfected by
      DNA/DOTMA complexes. These results suggest that inclusion of free liposomes into
      the DNA/lipid complexes may be important in achieving an optimal transfection
      activity in vivo.

PMID- 9651509
TI  - A role for Xenopus Frizzled 8 in dorsal development.
AB  - The establishment of cell and tissue polarity during animal development often
      requires signaling by Wnts, extracellular signaling polypeptides. Transmembrane
      receptors of the Frizzled family are implicated in the transduction of Wnt
      signals in responding cells. Xfz8 is a novel cDNA encoding a Xenopus homologue of
      mouse Frizzled 8. Xfz8 transcripts are expressed zygotically in the organizer at
      the early gastrula stage and in the most anterior ectoderm at later stages,
      suggesting a role in axis specification. When Xfz8 mRNA is overexpressed in
      ventral marginal zone cells, a secondary body axis with prominent head structures
      develops. Surprisingly, axis induction was not accompanied by activation of early
      dorsal marginal zone markers at the gastrula stages, whereas Xwnt8 induced these
      markers with high efficiency. These findings suggest that Xfz8 is a product of
      the organizer and mimics its function. Head induction by Xfz8 was blocked by co
      expression of GSK3beta or a dominant negative form of Xenopus Dishevelled,
      suggesting that this effect of Xfz8 requires Wnt signal transduction. When Xfz8
      is overexpressed in animal pole cells, dorsal marginal zone markers Xnr3, Xotx2
      and a promoter construct for Siamois, were selectively activated, demonstrating
      the difference in competence between animal pole cells and ventral marginal zone
      cells in response to Xfz8. It is proposed that the Wnt pathways are activated at
      two different steps during axis formation: to induce the Spemann organizer and to
      implement organizer functions by triggering dorsoanterior development.

PMID- 9651510
TI  - Identification of two Y-box binding proteins that interact with the promoters of
      columbid annexin I genes.
AB  - Two annexin I (anxI) genes, called cp35 and cp37, are expressed from the pigeon
      (Columba livia) genome, but they are regulated differently at both the
      transcriptional and post-transcriptional levels. The proximal promoter elements
      of these two genes are very similar. A conserved sequence from the cp35 and cp37
      promoters bound specifically with proteins present in cropsac cell extracts. This
      sequence of DNA was used to screen a lambdagt11 cDNA expression library. Clones
      encoding two pigeon Y-box binding proteins (YB) were isolated. One of the pigeon
      YB cDNAs was found to be most similar to YB1 from other species, and the other
      was most similar to chicken YB2. Each YB is encoded by a single-copy gene in the
      pigeon, and their mRNAs are expressed in many tissues. On Northern blots, the
      sizes of the mRNAs encoding pigeon YB1 (pYB1) and pigeon YB2 (pYB2) were 1.8 and
      1.7kb, respectively. The sequences of both pYB1 and pYB2 diverge from their
      previously identified relatives in the N-terminal domain 'A'. Antisera were
      developed to unique peptide epitopes in YB1 or 2. Affinity-purified anti-YB1 and
      anti-YB2 detected immunoreactive proteins in extracts from a variety of pigeon
      tissues, including the cropsac. To confirm that pYB1 and pYB2 interact with the
      cp35 promoter, electrophoretic gel mobility shift reactions were carried out in
      the presence or absence of YB antibodies. Binding to the cp35 promoter was
      specifically neutralized by either anti-pYB1 or anti-pYB2. These results are the
      first evidence that two YB proteins simultaneously bind to a promoter element,
      and thereby may interact during regulation of gene expression.

PMID- 9651511
TI  - Re-evaluation of the role of the dopamine transporter in dopamine system
      homeostasis.
AB  - Mice with a genetic deletion of the dopamine transporter (DAT) were used to
      assess its role in the function of dopamine (DA) neurons. Profound alterations in
      the homeostasis of the nigrostriatal DA system were induced by the absence of the
      DAT. Extracellular levels of DA were elevated and clearance of released DA was
      300-times slower than in control mice. This was accompanied by a 20-fold decrease
      in tissue DA levels and a paradoxical doubling of the rate of DA synthesis. A
      crucial role is indicated for the DAT in maintenance of DA neuron presynaptic
      function, particularly in the control of storage mechanisms.

PMID- 9651513
TI  - Neuropeptide Y: some viewpoints on a multifaceted peptide in the normal and
      diseased nervous system.
AB  - Using immunohistochemical and in situ hybridization methodologies the
      localization of neuropeptide tyrosine (NPY) and two of its receptors, the Y1- and
      the Y2-receptor (R), has been analysed in various tissues in normal animals and
      animals subjected to different experimental procedures as well as animals with a
      genetic and an acquired disease. (1) Dorsal root ganglion (DRG) neurons are
      discussed with special focus on the effect of peripheral nerve injury. In normal
      DRG neurons NPY cannot be detected, whereas Y1-R mRNA and Y1-R-like
      immunoreactivity (LI) are strongly expressed. The Y1-Rs decorate the membrane of
      the cell soma and are not transported peripherally into the axonal branches. Y2-R
      mRNA levels are low. After axotomy there is a marked increase in NPY, a decrease
      in Y1-Rs and an increase in Y2-Rs. The Y2-R is transported centrifugally. These
      findings suggest that NPY-ergic mechanisms participate in the adaptive changes of
      sensory neurons in response to injury. (2) Using specific antibodies the cellular
      and subcellular localization of the Y1-R protein have been analysed in cerebral
      blood vessels. The results demonstrate high concentrations of receptors in smooth
      muscle cells around pial arterioles with lower numbers in large vessels on the
      basal surface of the brain. In many regions the receptors 'disappear' after the
      arterioles have entered the brain tissue. At the ultrastructural level the
      receptors are found both on the endothelial and peripheral side of the muscle
      cells as well as laterally, where muscle cells oppose each other. The receptor
      protein is often associated with small vesicles. No NPY-positive nerve fibers
      were found around the Y1-R-rich arterioles, but they were only seen around the
      arteries with low Y1-R levels. The Y1-R-rich arterioles were, however, seen close
      to numerous NPY-positive fibers originating from central interneurons. These
      findings raise the possibility that centrally originating NPY can influence
      cerebral blood flow, possibly by stimulating NPY-Rs on the peripheral side of the
      muscle cells. However, also blood borne NPY, released under special conditions,
      such as stress from sympathetic nerves and the adrenal medulla and transported
      with blood, may stimulate receptors on the endothelial side of the smooth muscle
      cells. (3) In the arcuate nucleus Y1- and Y2-Rs are found, whereby the Y1-Rs are
      located in its ventro-medial portion and co-localized with POMC peptides, and the
      Y2-R in its ventromedial part, partly co-localized with NPY. NPY nerve endings
      makes synaptic contact with the POMC/Y1-R-positive neurons. In a mouse model for
      genetic anorexia very high levels of NPY were observed in arcuate neurons as
      compared to control mice. However, NPY mRNA levels were not different between the
      two groups. Taken together these findings are in good agreement with the view
      that NPY in the arcuate nucleus plays an important role in regulating feeding
      behaviour. (4) After intracerebral prion inoculation in mice an upregulation of
      NPY mRNA levels was observed in CA3 pyramidal neurons, and this effect was seen
      at a time point just before the first behavioural symptoms were manifested. At
      approximately the same time there was a dramatic decrease in Y2-R binding in
      strata oriens and radiatum of the CA1 region of the hippocampus, whereas in other
      regions no changes or much smaller changes were observed. Also, there was only a
      very slight decrease in Y2-R mRNA levels in CA3 neurons. It thus appears as if
      the prion disease prevents ligand binding to the Y2-R, perhaps by influencing
      traffic of receptor proteins, possibly at the level of cell membrane-associated
      caveolae, which have been implicated in the conversion of normal protein to
      scrapie protein. It is possible that these changes in NPY-ergic mechanisms may
      underlie some of the central symptoms associated with the prion disease.
      (ABSTRACT TRUNCATED)

PMID- 9651514
TI  - Sequence comparisons and functional studies of the proximal promoter of the
      carbonic anhydrase 3 (CA3) gene.
AB  - Carbonic anhydrase 3 (CA3) is a member of a gene family encoding proteins which
      catalyse the hydration of CO2 to generate protons and bicarbonate ions for
      cellular ion transport and pH homeostasis. In mouse embryos CA3 is expressed at
      high levels in notochord and skeletal muscle and here we demonstrate that this
      pattern of expression is the same in the developing human embryo. To investigate
      mechanisms controlling CA3 transcription, we have isolated and compared 2.8kb of
      sequence flanking exon 1 from the mouse and human genes. Several segments of high
      sequence identity >80% have been identified, the longest segments of which
      represent a proximal promoter region and a putative enhancer element. We have
      shown previously that in cultured cells the human 2.8kb promoter region imposes
      high level myogenic specific transcription of a reporter gene. However, we now
      show that while this promoter region directed muscle-specific expression in
      transgenic mouse embryos this was subject to position effects.

PMID- 9651515
TI  - Six3, a medaka homologue of the Drosophila homeobox gene sine oculis is expressed
      in the anterior embryonic shield and the developing eye.
AB  - The conserved transcription factor Pax6 is essential for eye development in
      Drosophila and mammals (Hill, R.E., Favor, J., Hogan, B.L.M., Ton, C.C.T.,
      Saunders, G.F., Hanson, I.M., Prosser, J., Jordan, T., Hastie, N.D., van
      Heyningen, V., 1991. Mouse small eye results from mutations in a paired-like
      homeobox containing gene. Nature 354, 522-525; Ton, C., Hirvonen, H., Miwa, H.,
      Weil, M., Monaghan, P., Jordan, T., van Heyningen, V., Hastie, N., Meijers
      Heijboer, H., Drechsler, M., Royer-Pokora, B., Collins, F., Swaroop, A., Strong,
      L.C., Saunders, G.F., 1991. Positional cloning and characterization of a paired
      box- and homeobox-containing gene from the aniridia region. Cell 6, 1059-1074;
      Matsuo, T., Osumi-Yamashita, N., Noji, S., Ohuchi, H., Koyama, E., Myokai, F.,
      Matsuo, N., Toniguchi, S., Dari, H., Jseki, S., Ninomiya, Y., Fujiwara, M.,
      Watanabe, T., Eto, K., 1993. A mutation at the Pax-6 gene in rat small eye is
      associated with impaired migration of midbrain crest cells. Nature genet. 3, 299
      304; Quiring, R., Walldorf, U., Kloter, U., Gehring, W.J., 1994. Homology of the
      eyeless gene of Drosophila to the small eye gene in mice and aniridia in humans.
      Science 265, 785-789). These findings led to the hypothesis that additional genes
      involved in invertebrate and vertebrate eye development are structurally and
      functionally conserved (Halder, G., Callaerts, P., Gehring, W.J., 1995. New
      perspectives on eye evolution. Curr. Opin. Gen. Dev. 5, 602-609; Quiring, R.,
      Walldorf, U., Kloter, U., Gehring, W.J., 1994. Homology of the eyeless gene of
      Drosophila to the small eye gene in mice and aniridia in humans. Science 265, 785
      789). Candidates for such conserved genes are the Drosophila homeobox gene sine
      oculis (Cheyette, B.N.R., Green, P.J., Martin, K., Garren, H., Hartenstein, V.,
      Zipursky, S.L., 1994. The Drosophila sine oculis locus encodes a homeodomain
      containing protein required for the development of the entire visual system.
      Neuron l2, 977-996) and its murine homologue Six3 (Oliver, G., Mailhos, A., Wehr,
      R., Copeland, N.G., Jenkins, N.A., Gruss, P., 1995. Six3, a murine homologue of
      the sine oculis gene, demarcates the most anterior border of the developing
      neural plate and is expressed during eye development. Development 121, 4045
      4055). sine oculis (so) is essential for the development of the larval and adult
      visual system (Cheyette, B.N.R., Green, P.J., Martin, K., Garren, H.,
      Hartenstein, V., Zipursky, S.L., 1994. The Drosophila sine oculis locus encodes a
      homeodomain-containing protein required for the development of the entire visual
      system. Neuron l2, 977-996). Six3 is expressed in the anterior neural plate and
      optic vesicles, lens, olfactory placodes and ventral forebrain (Oliver, G.,
      Mailhos, A., Wehr, R., Copeland, N.G., Jenkins, N.A., Gruss, P., 1995. Six3, a
      murine homologue of the sine oculis gene, demarcates the most anterior border of
      the developing neural plate and is expressed during eye development. Development
      121, 4045-4055). Overexpression of mouse Six3 gene in medaka fish embryos
      (Orvzias latipes) results in the formation of an ectopic lens, indicating that
      Six3 activity can trigger the genetic pathway leading to lens formation (Oliver,
      G., Loosli, F., Koster, R., Wittbrodt, J., Gruss, P., 1996. Ectopic lens
      induction in fish in response to the murine homeobox gene Six3. Mech. Dev. 60,
      233-239). We isolated the medaka Six3 homologue and analyzed its expression
      pattern in the medaka embryo. It is expressed initially in the anterior embryonic
      shield and later in the developing eye and prosencephalon. The early localized
      expression of Six3 suggests a role in the regionalization of the rostral head.

PMID- 9651516
TI  - Expression of T-box genes Tbx2-Tbx5 during chick organogenesis.
AB  - T-box genes encode putative transcription factors implicated in diverse
      developmental processes (Papaioannou, V.E. and Silver, L.M., 1998. BioEssays 20,
      9-19). We have previously reported the embryonic expression patterns of T-box
      genes in mice (Chapman, D.L., Garvey, N., Hancock, S., Alexiou, M., Agulnik,
      S.I., Gibson-Brown, J.J., Cebra-Thomas, J., Bollag, R.J., Silver, L.M.,
      Papaioannou, V.E., 1996. Dev. Dyn. 206, 379-390; Chapman, D.L., Agulnik, I.,
      Hancock, S., Silver, L.M. and Papaioannou, V.E., 1996. Dev. Biol. 180, 534-542;
      Gibson-Brown, J.J., Agulnik, S.I., Chapman, D.L., Alexiou, M., Garvey, N.,
      Silver, L.M., Papaioannou, V.E., 1996. Mech. Dev. 56, 93-101). Four of these
      genes (Tbx2-Tbx5) are represented in the mouse genome as two cognate, linked gene
      pairs (Agulnik, S.I., Garvey, N., Hancock, S., Ruvinsky, I., Chapman, D.L.,
      Agulnik, I., Bollag, R., Papaioannou, V.E., Silver, L.M., 1996. Genetics 144, 249
      254), and have all been implicated in playing important roles in limb development
      (Gibson-Brown, J.J., Agulnik, S.I., Chapman, D.L., Alexiou, M., Garvey, N.,
      Silver, L.M., Papaioannou, V.E., 1996. Mech. Dev. 56, 93-101). To investigate the
      role of these genes in limb development, we cloned the chicken orthologs and
      report functional studies, as well as patterns of expression in the developing
      limbs, elsewhere (Gibson-Brown, J.J., Agulnik, S.I., Silver, L.M., Niswander, L.,
      Papaioannou, V.E., Development, in press). This report details the patterns of
      expression of Tbx2-Tbx5 in chick embryonic tissues other than the limbs.

PMID- 9651517
TI  - Chromatin structure and functional analysis of the mouse HNF3alpha gene.
AB  - The transcription factor HNF3alpha is a member of the winged-helix family of
      regulatory proteins. It is expressed in the definitive endoderm, notochord, and
      neural tube in embryos, but in the adult is expressed primarily in endoderm
      derived tissues such as liver, lung, and pancreas. We present here the cloning of
      the mouse HNF3alpha gene and a characterization of its chromatin structure and
      regulatory sequences. The HNF3alpha gene is encoded by two exons and its
      transcription initiates at multiple start sites at a TATA-less promoter that is
      highly conserved between mouse and rat. We found different patterns of DNaseI
      hypersensitive sites in HNF3alpha gene chromatin in different adult tissues in
      which HNF3alpha is expressed, suggesting distinct regulatory mechanisms occurring
      within different tissue derivatives of the endoderm germ layer. Cell transfection
      data indicate that sequences spanning certain upstream hypersensitive sites can
      enhance transcription from the HNF3alpha promoter, but only when stably
      integrated into chromatin and not when transiently transfected. The results
      suggest a complex regulatory interplay between distinct genetic regulatory
      sequences that function specifically in chromatin.

PMID- 9651518
TI  - Nitric oxide and carbon monoxide: parallel roles as neural messengers.
AB  - Nitric oxide is now appreciated to be a molecule with important signaling
      functions in the body. The purification and cloning of the first NO synthesizing
      enzyme, NO synthase (NOS), from brain has led to the characterization of the
      roles of NO in normal physiology and in pathogenic states. NO synthesis is
      regulated in a complex manner, involving the association of activatory and
      inhibitory proteins. The body appears to use at least one other, highly related
      gas in a signaling function, carbon monoxide (CO). The enzyme responsible for CO
      biosynthesis in brain, heme oxygenase-2 (HO2), is rapidly regulated by
      neurotransmitter stimulation. The role for CO as neurotransmitter is suggested by
      the altered intestinal motility in mice harboring a genomic deletion of HO2.

PMID- 9651519
TI  - Immunohistochemical analysis of the expression of two serine-threonine kinases in
      the maturing mouse testis.
AB  - Previously we identified two intronless serine-threonine kinase genes (Tsk1 and
      Tsk2) located 3 kb apart on mouse chromosome 16 (Galili, N., Baldwin, H.S., Lund,
      J., Reeves, R., Gong, W., Wang, Z., Roe, B.A., Emanuel, B.S., Nayak, S.,
      Mickanin, C., Budraf, M.L., Buck, C.A., 1997. A region of mouse chromosome 16 is
      syntenic to the DiGeorge, velocardiofacial syndrome minimal critical region. Gen.
      Res. 7, 17-26). Tsk1 was identical to a putative testicular kinase reported by
      Bielke et al. (Bielke, W., Blaschke, R.J., Miescher, G.C., Zurcher, G., Andres,
      A.C., Ziemiecki, A., 1994. Characterization of a novel murine testis-specific
      serine/threonine kinase. Gene 13, 235-239). Here we document the expression
      patterns of each Tsk throughout spermiogenesis showing an initial association of
      Tsk1 with cells in meiotic metaphase and a later association of Tsk2 with tail
      like structures in the lumen of the seminiferous tubule.

PMID- 9651520
TI  - Comparison of the expression of three highly related genes, Fgf8, Fgf17 and
      Fgf18, in the mouse embryo.
AB  - In mammals, 16 members of the Fgf family have so far been described with diverse
      roles in embryonic cell growth and differentiation. Here, we report the
      expression from early streak stage to midgestation of two newly-identified murine
      genes, Fgf17 and Fgf18, that are most closely related to Fgf8 (63.7% and 56.8%
      identical, respectively, at the amino acid level). Fgf17 is expressed during
      gastrulation but at lower levels than Fgf8, while Fgf18 RNA is not expressed
      until later, in paraxial mesoderm. In the developing tail bud, each Fgf gene
      shows a different pattern of transcription. Distinct and overlapping expression
      patterns are also described in the developing brain and limbs.

PMID- 9651521
TI  - Gap junction wiring: a 'new' principle in cell-to-cell communication in the
      nervous system?
AB  - This review gives an updated excerpt of recent advances in our understanding of
      brain gap junctions. It starts with a brief description of the principle
      molecular composition of gap junctions before specific issues concerning brain
      tissues are addressed. The following questions and matters are subjected to a
      detailed analysis: First, why are there so many gap junctions in the brain?
      Second, what is the functional significance of the cellular diversity of brain
      gap junctions? Third, how do astrocytic gap junctions mediate intercellular
      volume transmission (IVT), and what does IVT mean for glial-neuronal interaction?
      Fourth, how frequent are interneuronal gap junctions; and what is their
      functional significance in brain development and in interrelated chemical
      electrotonic transmission at mixed synapses.

PMID- 9651522
TI  - Mouse submandibular gland mucin: embryo-specific mRNA and protein species.
AB  - Mouse submandibular salivary gland (SMG) mucin is the primary
      histodifferentiation product of submandibular epithelia. We demonstrate marked
      differences between embryonic, neonatal, and adult SMG mucin mRNA and protein by
      Northern and Western blot analyses: E17 and 1-day-old neonates exhibit two unique
      mucin transcripts (1.20 and 0.85 kb) which are approximately 19% greater or
      smaller in size than the single (1.01 kb) adult transcript. Two embryonic protein
      isoforms (Mr approximately 110 and 152 kDa) are immunodetected compared to a
      single adult protein (Mr approximately 136 kDa), with the larger (approximately
      152 kDa) embryonic isoform persisting in neonatal glands. Mucin transcripts are
      localized to the branching epithelia in E14 and older SMGs, with increased
      hybridization signal being seen in terminal bud and proacinar epithelial cells
      with age; a significant 26% increase in transcript levels is detected by RNase
      protection assay between E14 and E19. By contrast, submandibular mucin protein is
      not immunodetected until E17, being primarily immunolocalized to terminal bud and
      proacinar epithelial cell membranes. Our data clearly shows that substantial
      qualitative differences exist between embryonic and adult SMG mucin mRNA and
      protein.

PMID- 9651523
TI  - Intrinsic function of a neuronal network - a vertebrate central pattern
      generator.
AB  - The cellular bases of vertebrate locomotor behaviour is reviewed using the
      lamprey as a model system. Forebrain and brainstem cell populations initiate
      locomotor activity via reticulospinal fibers activating a spinal network
      comprised of glutamatergic and glycinergic interneurons. The role of different
      subtypes of Ca2+ channels, Ca2+ dependent K+ channels and voltage dependent NMDA
      channels at the neuronal and network level is in focus as well as the effects of
      different metabotropic, aminergic and peptidergic modulators that target these
      ion channels. This is one of the few vertebrate networks that is understood at a
      cellular level.

PMID- 9651524
TI  - Highly restricted expression at the ectoderm-endoderm boundary of PIHbox 9, a sea
      urchin homeobox gene related to the human HB9 gene.
AB  - Characterisation of a sea urchin (P. lividus) homeobox gene PIHbox 9 is reported.
      The homeodomain of PIHbox9 is 95% identical to the homeodomain of the human HB9
      gene, indicating that the two genes are highly related. Temporal expression
      analysis during sea urchin embryogenesis showed an absence of transcripts at
      early cleavage stages. At late gastrula stage, transcripts were barely detectable
      and reached the highest abundance at prism/early pluteus stages. By whole mount
      in situ hybridisation we observed a highly restricted expression in a few cells
      of the ectoderm-endoderm boundary of embryos at the prism stage. At pluteus
      stages, expression of PIHbox 9 was confined around the anus.

PMID- 9651525
TI  - Genomic structure and isoform expression of the mouse, rat and human Cbfa1/Osf2
      transcription factor.
AB  - Although the CBFA1 gene encodes an osteoblast-specific transcription factor that
      regulates osteoblast differentiation, uncertainty exists about the organization
      of its 5' end and the relevance of a novel N-terminal sequence identified in the
      mouse Cbfa1/Osf2 isoform. We found the novel 5' Cbfa1/Osf2 sequence is encoded by
      a previously unrecognized upstream exon, designated exon -1, which is highly
      conserved in mouse, rat and human. In addition, two splice donor sites may be
      utilized to generate Cbfa1/Osf2 cDNAs containing different N-terminal sequences.
      The first ATG and splice donor site in exon -1 is predicted to transcribe a cDNA
      containing the unique Osf2 5' sequence, whereas a second donor splice site gives
      rise to cDNAs that contain sequences encoding an 11 amino acid insert. In the
      human CBFA1 gene, an additional 2-bp nucleotide insert shifts the reading frame
      and results in stop codons in the cDNA sequence derived from exon -1. The 5'-most
      exon of the human CBFA1 gene, therefore, contains the 5' non-coding region rather
      than a human OSF2 homolog. The absence of a homologous OSF2 coding sequence in
      the human CBFA1 cDNA suggests that the novel mouse N-terminal Osf2 sequence is
      not essential for functioning of the CBFA1 gene product. In addition, multiple
      transcripts derived from a single CBFA1/Cbfa1 gene were detected in osteoblasts
      by Northern analysis and RT-PCR, including additional Cbfa1/Osf2 isoforms
      containing deletions of exons 1 and 4. Thus, the alternative use of transcription
      start sites and splicing leads to the genesis of CBFA1/Cbfa1 isoforms with
      possible differences in transactivation potentials.

PMID- 9651526
TI  - MDM2 expression during mouse embryogenesis and the requirement of p53.
AB  - We compared mouse embryonic expression of the MDM2 proto-oncogene, p21WAF1/CIP1
      and their transcriptional regulator, p53. MDM2 expression is ubiquitous from 7.5
      to 11.5 days post coitum (dpc) and more restricted from 12.5 dpc, with the
      highest levels in the testes and neural tube. From 14.5 to 18.5 dpc, the nasal
      respiratory epithelium expresses high levels of MDM2 RNA and protein and
      p21WAF1/CIP1 RNA, in both wild type and p53 null embryos. MDM2 expression during
      development is tissue-specific and, like p21WAF1/CIP1, is independent of p53.
      MDM2 may have a developmental role after 6.5 dpc, when MDM2 null mice die (Jones,
      S.N., Roe, A.E., Donehower, L.A., Bradley, A., 1995. Rescue of embryonic
      lethality in Mdm2-deficient mice by absence of p53. Nature 378, 206-208; Montes
      de Oca Luna, R., Wagner, D.S., Lozano, G., 1995. Rescue of early embryonic
      lethality in mdm2-deficient mice by deletion of p53. Nature 378, 203-206).

PMID- 9651527
TI  - Brain nicotinic receptors: structure and regulation, role in learning and
      reinforcement.
AB  - The introduction, in the late sixties, of the concepts and methods of molecular
      biology to the study of the nervous system had a profound impact on the field,
      primarily through the identification of its basic molecular components. These
      structures include, for example, the elementary units of the synapse:
      neurotransmitters, neuropeptides and their receptors, but also ionic channels,
      intracellular second messengers and the relevant enzymes, cell surface adhesion
      molecules, or growth and trophic factors [21,78,81, 52,79]. Attempts to establish
      appropriate causal relationships between these molecular components, the actual
      organisation of neural networks, and a defined behavior, nevertheless, still must
      overcome many difficulties. A first problem is the recognition of the minimum
      levels of organisation, from the molecular, cellular, or multicellular (circuit)
      to the higher cognitive levels, that determine the given physiological and/or
      behavioral performance under investigation. A common difficulty (and potential
      source of errors of interpretation) is to relate a cognitive function to a
      network organization which does not possess the required structural complexity
      and vice-versa. Another problem is to distinguish, among the components of the
      system, those which are actually necessary and those which, taken together,
      suffice for a given behavior to take place. Identification of such a minimal set
      of building blocks may receive decisive insights from the elaboration of neurally
      plausible formal models that bring together, within a single and coherent
      'artificial organism', the neuronal network, the circulating activity, and the
      behavior they determine (see [42,43,45,72,30]). In this communication, we shall
      attempt, still in a preliminary fashion, to bring together: (1) our recent
      knowledge on the molecular biology of brain nicotinic receptors (nAChRs) and
      their allosteric properties and (2) integrated behaviors, such as cognitive
      learning, investigated for instance with delayed-response or passive avoidance
      tasks that are likely to involve nAChRs in particular at the level of
      reinforcement (or reward) mechanisms (see [18,29,135]).

PMID- 9651528
TI  - Cloning of 5'-flanking region and a polymorphic CTT trinucleotide repeat within
      5'-untranslated region of mouse R-type calcium channel alpha1-subunit (Cchra1)
      gene, and its genetic mapping.
AB  - The 5'-flanking region of the mouse R-type calcium channel (Cchra1) gene was
      cloned, and a transcriptional start point (tsp) was determined by rapid
      amplification of 5'-cDNA end (5'RACE) method. The putative promoter region of the
      gene contained no obvious TATA or CCAAT element in the expected positions, but
      multiple putative binding sites for transcriptional factors, such as Sp1, AP-1,
      AP-2, AP-3, EGR-1, EGR-2, NF-kappaB and HIP1, were detected. We found the
      existence of a tandem CTT trinucleotide repeat within the 5'-untranslated region
      (UTR) of the gene, and its polymorphism between C57BL/6J and Mus spretus. Using
      this polymorphism, the Cchra1 was mapped to the region of chromosome 1 where the
      synteny to human chromosome 1q was conserved.

PMID- 9651529
TI  - Eubacterial origin of nuclear genes for chloroplast and cytosolic glucose-6
      phosphate isomerase from spinach: sampling eubacterial gene diversity in
      eukaryotic chromosomes through symbiosis.
AB  - Higher plants possess two distinct nuclear-encoded glucose-6-phosphate isomerase
      (GPI) isoenzymes, a cytosolic enzmye of the Embden-Meyerhof pathway and a
      chloroplast enzyme essential to storage and mobilization of carbohydrate fixed by
      the Calvin cycle. We have purified spinach chloroplast GPI to homogeneity,
      determined amino acid sequences from the active enzyme, and cloned cDNAs for
      chloroplast and cytosolic GPI isoenzymes from spinach. Sequence comparisons
      reveal three distantly related families of GPI genes that are non-uniformly
      distributed among contemporary eubacteria and archaebacteria, suggesting that
      ancient gene diversity existed for this glycolytic enzyme. Spinach chloroplast
      GPI is much more similar to its homologue from the cyanobacterium Synechocystis
      PCC6803 than it is to the enzyme from any other source, providing strong evidence
      that the gene for chloroplast GPI was acquired by the nucleus via endosymbiotic
      gene transfer from the cyanobacterial antecedants of chloroplasts. Eukaryotic
      nuclear genes for cytosolic GPI are more similar to eubacterial than to
      archaebacterial homologues, suggesting that these too were acquired by eukaryotes
      from eubacteria, probably during the course of the endosymbiotic origin of
      mitochondria. Chloroplast and cytosolic GPI provide evidence for a eubacterial
      origin of yet another component of the eukaryotic glycolytic pathway.

PMID- 9651530
TI  - Isolation of a novel metabolizing system enriched in phase-II enzymes for short
      term genotoxicity bioassays.
AB  - Murine S9 liver fractions isolated from mice fed 7.5 g kg-1 2(3)-tert-Butyl-4
      hydroxyanisole (BHA) for 3 weeks were tested to determine: (a) the profile of
      both phase-I and phase-II xenobiotic metabolizing enzymes; (b) their ability to
      induce in vitro covalent binding of some precarcinogens to calf thymus DNA; and
      (c) their activation in a standard genetic toxicology assay. With regard to phase
      I pathway, the S9 fraction expressed various cytochrome P-450-(CYP) (classes 1A1,
      1A2, 2B1, 2E1, and 3A)-dependent biotransformation enzymes at levels comparable
      with those present in murine control liver. For post-oxidative enzymes, the S9
      expressed high levels of glutathione S-transferases (up to 12-fold increase),
      glutathione S-epoxide-transferase (up to 2.6-fold), UDP-glucuronosyl transferase
      (up to 5.3-fold) and epoxide hydrolase (up to 2.6-fold) activities, as compared
      to untreated mice. The in vitro DNA binding of the precarcinogenic agents [14C]
      1,4-dichlorobenzene, [14C]-1,2-dichlorobenzene and [14C]-1,4-dibromobenzene,
      mediated by BHA-induced cytosol and/or microsomal preparation, showed an increase
      in specific activity comparable to that observed with phase-I (PB/beta NF)
      induced S9. In some instances, covalent binding was even more elevated using the
      BHA-induced systems as compared with traditional S9 fractions. For example,
      cytosol derived from BHA-administered mice was able to induce a significant
      binding to calf thymus DNA up to 26.2-fold increase for [14C]-1,4
      dichlorobenzene, while cytosol from PB/beta NF was not. A high mutagenic response
      on diploid D7 strain of Saccharomyces cerevisiae as exemplified by a marked
      induction of mitotic gene conversion and point (reverse) mutation confirmed that
      BHA-derived S9 fractions activate precarcinogens to final genotoxins. Because a
      number of chemicals are activated by either oxidative or post-oxidative enzymes,
      the use of metabolizing biosystems, with an enhanced phase-II pathway, together
      with classical S9 fractions, can improve the sensitivity of the assay in
      detecting unknown genotoxins.

PMID- 9651532
TI  - RNA editing of brain glutamate receptor channels: mechanism and physiology.
AB  - Glutamate-gated cation selective channels mediate fast excitatory
      neurotransmission in the mammalian brain. Functionally critical channel positions
      contain amino acid residues not predicted from the exonic sequence for the
      channel subunits. The codons for these residues are created in the respective
      primary gene transcripts by the site selective deamination of adenosine to
      inosine. This type of RNA editing requires a short double-stranded RNA structure
      formed by the exonic sequence around the adenosine targeted for deamination with
      a complementary sequence in the downstream intron and hence, it precedes
      splicing. Candidate enzymes for nuclear transcript editing currently comprise
      three molecularly cloned mammalian RNA-dependent adenosine deaminases. Two of
      these are expressed in most body tissues, perhaps indicating that adenosine
      deamination in transcripts is more global than has been recognized. Indeed,
      numerous mRNAs in different tissues may contain inosine residues and encode
      proteins with amino acid substitutions and different properties relative to the
      exonically encoded forms. If so, RNA editing by adenosine deamination may
      significantly enlarge the functional repertoire of the mammalian genome.

PMID- 9651531
TI  - Genomic organization and cloning of the human homologue of murine Sipa-1.
AB  - Murine Sipa-1 (signal-induced proliferation associated protein) is a mitogen
      induced GTPase activating protein (GAP). While mapping candidate genes for
      multiple endocrine neoplasia type 1 (MEN1) at 11q13, we cloned the human
      homologue of Sipa-1. Herein, we report the complete cDNA sequence, expression,
      and genomic organization of SIPA-1. SIPA-1 consists of 16 exons with highly
      conserved exon-intron boundaries. The predicted SIPA-1 protein is highly
      homologous to the mouse protein, particularly in the region of the GAP-related
      domain at the amino terminus and the leucine zipper at the carboxy terminus. It
      is widely expressed, including in fetal tissues, but is most highly expressed in
      lymphoid organs. During the course of cloning SIPA-1, the MEN1 gene was
      identified, thus excluding human SIPA-1 as a candidate for this disease.

PMID- 9651533
TI  - Development of new tester strains derived from E. coli WP2uvrA for the
      determination of mutational specificity.
AB  - We have developed a set of multipurpose tester strains (WP3101 to WP3106) derived
      from E. coli WP2uvrA for the detection and classification of mutagens. Six kinds
      of F' plasmid (lacI, lacZ, proAB+) in strains CC101-CC106, each of which carried
      a different lacZ allele, were transferred to a delta(lac-pro) derivative of
      WP2uvrA. Assays for transitions and transversions are based upon Lac+ reversion
      of a specific mutation located within the lacZ gene on an F' plasmid in strains
      WP3101-WP3106. In addition, the trpE65(ochre) allele in the same strains is
      available for Trp+ reversion assays. Using the new tester strains, we
      investigated the mutational specificities of various chemical mutagens. Base
      analog mutagens and alkylating mutagens induced specific types of base
      substitutions. G:C-->A:T transitions and G:C-->T:A transversions predominated in
      mutagenesis induced by 4-nitroquinoline 1-oxide. Only a slight increase in G:C-
      >T:A transversions was observed in cells treated with 2-(2-furyl)-3-(5-nitro-2
      furyl)acrylamide (AF-2), although the potent mutagenicity of AF-2 was detected in
      a concurrent Trp+ reversion assay in the same strain. Sodium azide, on the other
      hand, was negative in the Trp+ reversion assay but specifically induced G:C-->A:T
      transitions. Present finding suggested that target sites for AF-2- and azide
      induced lesions may largely depend on sequence context.

PMID- 9651534
TI  - Modulation of mitomycin C-induced sister chromatid exchanges and cell cycle delay
      by buthionine sulfoximine and reduced glutathione in mouse bone marrow cells in
      vivo.
AB  - Mitomycin C (MMC) is a bifunctional alkylating agent and a chemotherapeutic drug,
      covalently binds to the DNA of cells and produces monoadducts and DNA-DNA, DNA
      protein crosslinks, induces damages at chromosomal level and slows down the rate
      of cell proliferation. Reduced glutathione (GSH), a major non-protein thiol
      substance plays an important role in detoxification of cells against the toxic
      effect of exogenous compounds. In order to understand the role of factor which
      affects MMC sensitivity, we have made an attempt to establish a relationship
      between MMC-induced DNA damages and the endogenous GSH-status of the cells. MMC
      was treated to normal and buthionine sulfoximine (BSO; GSH-depleting agent)
      treated mice. Exogenous GSH was also added to MMC-treated normal mice. Cells were
      fixed at 24 h and sister chromatid exchanges (SCEs) and average generation time
      (AGT) were scored. MMC-induced SCEs and cell cycle delay significantly with
      respect to control and the frequency of SCEs was increased considerably while MMC
      treatment combined with either GSH or BSO. The induction of cell cycle delay by
      MMC was reduced significantly when GSH or BSO was present along with MMC. These
      observations indicate that the factor responsible for inducing delay in cell
      cycle after MMC treatment may not be relevant for SCE-induction.

PMID- 9651535
TI  - Glutamate receptors: brain function and signal transduction.
AB  - Glutamate receptors are important in neural plasticity, neural development and
      neurodegeneration. N-methyl-d-aspartate (NMDA) receptors and alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate receptors act as glutamate
      gated cation channels, whereas metabotropic receptors (mGluRs) modulate the
      production of second messengers via G proteins. Molecular studies from our and
      other laboratories indicated that NMDA receptors and mGluRs exist as multiple
      subunits (NMDAR1 and NMDAR2A-2D) and multiple subtypes (mGluR1-mGluR8). In light
      of the molecular diversity of glutamate receptors, we explored the function and
      intracellular signaling mechanisms of different members of glutamate receptors.
      In the visual system, retinal bipolar cells receive glutamate transmission from
      photoreceptors and contribute to segregating visual signals into ON and OFF
      pathways. The molecularly cloned mGluR6 is restrictedly expressed at the
      postsynaptic site of ON-bipolar cells in both rod and cone systems. Gene
      targeting of mGluR6 results in a loss of ON responses without changing OFF
      responses and severely impairs detecting visual contrasts. Since AMPA receptors
      mediate OFF responses in OFF-bipolar cells, two distinct types of glutamate
      receptors effectively operate for ON and OFF responses. mGluR1 and mGluR5 are
      both coupled to inositol triphosphate (IP3)/calcium signal transduction with an
      identical agonist selectivity. Single-cell intracellular calcium ([Ca2+]i)
      recordings indicated that glutamate evokes a non-oscillatory and oscillatory
      [Ca2+]i response in mGluR1-expressing and mGluR5-expressing cells, respectively.
      This difference results from a single amino acid substitution, aspartate of
      mGluR1 or threonine of mGluR5, at the G protein-interacting carboxy-terminal
      domains. Protein kinase C phosphorylation of the threonine of mGluR5 is
      responsible for inducing [Ca2+]i oscillations in mGluR5-expressing cells and
      cultured glial cells. Thus, the two closely related mGluR subtypes mediate
      diverging intracellular signaling in glutamate transmission.

PMID- 9651536
TI  - Caged amphibian tadpoles and in situ genotoxicity monitoring of aquatic
      environments with the alkaline single cell gel electrophoresis (comet) assay.
AB  - In previous studies we demonstrated that indigenous amphibian tadpoles are
      suitable organisms for monitoring small bodies of water (e.g., creeks, ponds, and
      drainage ditches) using the alkaline single cell gel electrophoresis (SCG) or
      'comet' assay. This approach involves detection, under alkaline conditions, of
      cell DNA fragments which on electrophoresis migrate from the nuclear core,
      resulting in a 'comet with tail' formation. However, although often plentiful,
      tadpoles are not present in all aquatic environments. Both larger bodies of water
      (e.g., lakes and rivers) and those impacted upon heavily by man (e.g., bodies of
      water near industrial sites, on landfills, and in urban areas) often do not
      support amphibian tadpole populations. An alternative approach to the collection
      of indigenous tadpoles is to place caged tadpoles at these sites for short term
      exposures to environmental contaminants. To determine the feasibility of such an
      approach, Rana clamitans (green frog) and Bufo americanus (American toad)
      tadpoles were housed in cages at 11 sites in southwestern Ontario (Canada). In a
      preliminary experiment, we found that tadpoles caged at a polluted reference site
      (Tallgrass Prairie Heritage Park in Windsor, Ontario) for either 7 or 14 days
      showed significant (P < 0.05) increases in DNA damage, relative to tadpoles caged
      in the laboratory in dechlorinated water. As a result we routinely used a 7 day
      exposure time. Significantly (P < 0.05) increased levels of DNA damage, relative
      to their controls, were observed in tadpoles caged at three sites along two
      creeks draining a large petrochemical installation south of Sarnia, Ontario; at
      two sites in the Tallgrass Prairie Heritage Park; and at a site along the Ecarte
      Channel which is part of the St. Clair River. The DNA damage levels of animals
      caged in Lake St. Clair, in the Trenton Channel of the Detroit River, at a
      landfill site, and in two creeks in the city of Windsor did not differ
      significantly (P > 0.05) from their controls. This study demonstrates that caged
      tadpoles are suitable for monitoring most bodies of fresh water, particularly
      those aquatic habitats mentioned above where indigenous tadpoles are not present.
      A combined approach of collecting indigenous tadpoles and using caged tadpoles
      should provide a sensitive system for aquatic genotoxicity monitoring.

PMID- 9651537
TI  - Functional implications of multiple dopamine receptor subtypes: the D1/D3
      receptor coexistence.
AB  - The D3 dopamine receptor, a D2-like receptor, is selectively expressed in the
      ventral striatum, particularly in the shell of nucleus accumbens and islands of
      Calleja, where it is found in medium sized substance P neurons. The latter co
      express the D1 receptor whose interaction with the D3 receptor was studied by
      treating rats with selective agonists and antagonists. In agreement with the
      opposite cAMP response, they mediate in cultured neuroblastoma cells, the D1 and
      D3 receptors exerted opposite influences on c-fos expression in islands of
      Calleja. However, in agreement with the synergistic influence of cAMP on D3
      receptor-mediated mitogenesis on the same cultured cells, D1 and D3 receptor
      stimulation in vivo synergistically enhanced preprotachykinin mRNA in the shell
      of accumbens. This indicates that the two receptor subtypes may affect neurons in
      either synergy or opposition according to the cell or signal generated. Levodopa
      induced behavioral sensitization in hemiparkinsonian rats is another example of
      D1/D3 receptor interaction. Hence repeated levodopa administration induces the
      ectopic appearance of the D3 receptor in substance P/dynorphin, striatonigral
      neurons of the dorsal striatum. This induction is secondary to D1 receptor
      stimulation in neurons of the denervated side and fully accounts for the
      sensitization, i.e. the increased behavioral responsiveness to levodopa. During
      brain development, a similar process could operate to control the late appearance
      of the D3 receptor in D1-receptor bearing neurons of the ventral striatum at a
      time at which they start to be innervated by dopamine neurons. Finally, taking
      into account a variety of genetic, developmental, neuroimaging and
      pharmacological data, we postulate that imbalances between the levels of D1 and
      D3 receptors in the same neurons could be responsible for schizophrenic
      disorders.

PMID- 9651538
TI  - Signal transduction molecules at the glutamatergic postsynaptic membrane.
AB  - We have applied techniques from modern molecular biology and biochemistry to
      unravel the complex molecular structure of the postsynaptic membrane at
      glutamatergic synapses in the central nervous system. We have characterized a set
      of new proteins that are constituents of the postsynaptic density, including PSD
      95, densin-180, citron (a rho/rac effector protein), and synaptic gp130 Ras GAP
      (a new Ras GTPase-activating protein). The structure of PSD-95 revealed a new
      protein motif, the PDZ domain, that plays an important role in the assembly of
      signal transduction complexes at intercellular junctions. More recently, we have
      used new imaging tools to observe the dynamics of autophosphorylation of CaM
      kinase II in intact hippocampal tissue. We have been able to detect changes in
      the amount of autophosphorylated CaM kinase II in dendrites, individual synapses,
      and somas of hippocampal neurons following induction of long-term potentiation by
      tetanic stimulation. In addition, we have observed a specific increase in the
      concentration of CaM kinase II in dendrites of neurons receiving tetanic
      stimulation. This increase appears to be the result of dendritic synthesis of new
      protein. Over the next several years we will apply similar methods to study
      regulatory changes that occur at the molecular level in glutamatergic synapses in
      the CNS as the brain processes and stores new information.

PMID- 9651539
TI  - Random population-wide genetic damage induced in replicating cells treated with
      methotrexate.
AB  - Low lethality treatment of the NIH 3T3 mouse cell line with methotrexate (MTX)
      during exponential multiplication results in heterogeneous, heritable reduction
      in growth rate of most if not all the replicatively surviving cells. The
      effective concentrations of MTX are 10 to 100 times higher in molecular, cellular
      and developmental biology medium 402 (MCDB 402) than in Dulbecco's modification
      of Eagle's medium (DMEM) medium because of the folate-sparing presence of
      adenine, thymidine and, particularly, of folinic acid in MCDB 402 medium. The
      reduced growth rates are detectable during early passages of surviving
      populations before the faster growing cells dominate them. The heritable effect
      is most clearly demonstrated by sequestered cloning of many individual cells
      immediately after drug treatment, and repeatedly measuring the growth rates of
      the clones in serial passages. After 7-10 passages of the clones, there is an
      increase in growth rate of some of the slow growing clones presumably due to the
      generation and selection of faster growing cells. Evidence from mutagenic studies
      at a single genetic locus in other cell lines suggests that heritable reductions
      in growth rate arise from chromosome aberrations although point mutations may
      also contribute to the effect. Clastogenic changes can be induced by a wide
      variety of mutagens and carcinogens, many of which are used in chemotherapy of
      cancer and other chronic diseases. The population-wide, heritable damage to cells
      may be the source of, or may contribute to, late-occurring side effects of
      treatment in cancer and other chronic diseases.

PMID- 9651540
TI  - Integrated events in central dopamine transmission as analyzed at multiple
      levels. Evidence for intramembrane adenosine A2A/dopamine D2 and adenosine
      A1/dopamine D1 receptor interactions in the basal ganglia.
AB  - An analysis at the network and membrane level has provided evidence that
      antagonistic interactions between adenosine A2A/dopamine D2 and adenosine
      A1/dopamine D1 receptors in the ventral and dorsal striatum are at least in part
      responsible for the motor stimulant effects of adenosine receptor antagonists
      like caffeine and for the motor depressant actions of adenosine receptor
      agonists. The results obtained in stably cotransfected cells also underline the
      hypothesis that the intramembrane A2A/D2 and A1/D1 receptor interactions
      represent functionally important mechanisms that may be the major mechanism for
      the demonstrated antagonistic A2A/D2 and A1/D1 receptor interactions found in
      vivo in behavioural studies and in studies on in vivo microdialysis of the
      striopallidal and strioentopeduncular GABAergic pathways. A major mechanism for
      the direct intramembrane A2A/D2 and A1/D1 receptor interactions may involve
      formation of A2A/D2 and A1/D1 heterodimers leading to allosteric changes that
      will alter the affinity as well as the G protein coupling and thus the efficacy
      to control the target proteins in the membranes. This is the first molecular
      network to cellular integration in the nerve cell membrane and may be well suited
      for a number of integrated tasks and can be performed in a short-time scale, in
      comparison with the very long-time scale observed when receptor heteroregulation
      involves phosphorylation or receptor resynthesis. Multiple receptor-receptor
      interactions within the membranes through formation of receptor clusters may lead
      to the storage of information within the membranes. Such molecular circuits can
      represent hidden layers within the membranes that substantially increase the
      computational potential of neuronal networks. These molecular circuits are biased
      and may therefore represent part of the molecular mechanism for the storage of
      memory traces (engrams) in the membranes.

PMID- 9651541
TI  - Mutagenicity of three disinfection by-products: di- and trichloroacetic acid and
      chloral hydrate in L5178Y/TK +/- (-)3.7.2C mouse lymphoma cells.
AB  - The disinfection of water, required to make it safe for human consumption, leads
      to the presence of halogenated organic compounds. Three of these carcinogenic
      'disinfection by-products', dichloroacetic acid (DCA), trichloroacetic acid (TCA)
      and chloral hydrate (CH) have been widely evaluated for their potential toxicity.
      The mechanism(s) by which they exert their activity and the steps in the etiology
      of the cancers that they induce are important pieces of information that are
      required to develop valid biologically-based quantitative models for risk
      assessment. Determining whether these chemicals induce tumors by genotoxic or
      nongenotoxic mechanisms (or a combination of both) is key to this evaluation. We
      evaluated these three chemicals for their potential to induce micronuclei and
      aberrations as well as mutations in L5178Y/TK +/- (-)3.7.2C mouse lymphoma cells.
      TCA was mutagenic (only with S9 activation) and is one of the least potent
      mutagens that we have evaluated. Likewise, CH was a very weak mutagen. DCA was
      weakly mutagenic, with a potency (no. of induced mutants/microgram of chemical)
      similar to (but less than) ethylmethanesulfonate (EMS), a classic mutagen. When
      our information is combined with that from other studies, it seems reasonable to
      postulate that mutational events are involved in the etiology of the observed
      mouse liver tumors induced by DCA at drinking water doses of 0.5 to 3.5 g/l, and
      perhaps chloral hydrate at a drinking water dose of 1 g/l. The weight-of-evidence
      for TCA suggest that it is less likely to be a mutagenic carcinogen. However,
      given the fact that DCA is a weak mutagen in the present and all of the published
      studies, it seems unlikely that it would be mutagenic (or possibly carcinogenic)
      at the levels seen in finished drinking water.

PMID- 9651542
TI  - The DARPP-32/protein phosphatase-1 cascade: a model for signal integration.

PMID- 9651543
TI  - Determination of diesel genotoxicity in firebreathers by micronuclei and nuclear
      abnormalities in buccal mucosa.
AB  - Diesel or its derivatives could have aneuploidogenic and/or clastogenic activity.
      Hence, the genotoxicity of diesel gases has been studied, considering exposure to
      them as potentially carcinogenic. The results obtained by different authors
      suggest the need to know the effects of direct and chronic exposure to diesel in
      humans, as in the case of the street workers called 'firebreathers' who fill
      their buccal cavity with diesel and then spread it to a burning torch many times
      during the day in order to give a 'dragon show' for 5 h a day and 6 days a week.
      The buccal samples of eight firebreathers were collected, processed and scored
      according to the criterion established by Tolbert et al., 1992 and then compared
      with positive and negative control groups. The results revealed that diesel was
      not micronucleogenic although it induces some nuclear abnormalities.

PMID- 9651544
TI  - Role of reelin in the control of brain development.
AB  - Reeler is an autosomal recessive mutation in mice that results in widespread
      disruption of laminated regions of the brain. We isolated a gene, reelin, that is
      mutated in reeler mice. The protein product of reelin has features of
      extracellular matrix components and it is expressed in a temporal and spatial
      pattern during embryonic and postnatal development consistent with the phenotypic
      defects in reeler mice. To understand the molecular basis of the function of
      Reelin, we constructed a full length reelin clone and used it to direct Reelin
      expression. Using this clone we found that Reelin is a secreted glycoprotein and
      that a highly charged C-terminal region is essential for secretion. Furthermore,
      we demonstrated that an amino acid sequence present in the N-terminal region of
      Reelin contains an epitope that is recognized by the CR-50 monoclonal antibody.
      CR-50 was raised against an antigen expressed in normal mouse brain that is
      absent in reeler mice. The interaction of CR-50 with its epitope has been shown
      to disrupt neuronal migration in vitro and in vivo. We used CR-50 to precipitate
      p385 Reelin from reticulocyte extracts programmed with reelin mRNA, from cells
      transfected with reelin clones and from cerebellar explants. Reelin appears to
      function as an instructive signal in the regulation of cell patterning during
      development.

PMID- 9651545
TI  - Neurotrophin receptors: mediators of life and death.
AB  - The mechanism of action of NGF has continued to provide a challenging and
      formidable problem in signal transduction. NGF can bind independently to two
      different receptors, the trkA tyrosine kinase receptor and the p75 neurotrophin
      receptor, which are involved in many different signaling events. In addition to
      promoting cell differentiation survival, NGF can paradoxically be an inducer of
      cell death. Several receptor mediated mechanisms are proposed to explain how NGF
      might act as a trophic factor and as a cell killer. The survival and cell death
      properties of the receptors are dependent upon the relative ratio of receptors
      and the persistent nature of the signaling events.

PMID- 9651546
TI  - On CNS repair and protection strategies: novel approaches with implications for
      spinal cord injury and Parkinson's disease.
AB  - In the adult mammalian central nervous system lost nerve cells are not replaced
      and there is no regeneration of injured axons in white matter. Together, these
      two facts mean that there are no spontaneous reparative mechanisms in operation.
      Instead, the adult central nervous system copes with the risks of injuries and
      diseases by protective encapsulation in bone, by a multitude of neuroprotective
      mechanisms, and finally by the fact that many important functions are represented
      by a much larger number of neurons than minimally needed. The long life
      expectancy of a human being nevertheless means that the risk that the central
      nervous system is affected by disease, injury or other forms of insults for which
      it cannot fully compensate is relatively high. Experimentally, two strategies are
      being pursued in order to develop ways of minimizing various forms of CNS damage,
      namely neuroprotective and reparative strategies. Here we present a possible
      reparative intervention applicable to spinal cord injury based on multiple white
      to-gray matter peripheral nerve bridge grafts and work based on the specific role
      of Nurr1 for dopamine neuron development, suggesting that development of ligands
      to transcription factor might be a new inroad to neuroprotective treatments in
      Parkinson's disease.

PMID- 9651547
TI  - Interleukin-1 receptors: cloning studies and role in central nervous system
      disorders.

PMID- 9651548
TI  - Inflammatory cytokines: putative regulators of neuronal and neuro-endocrine
      function.
AB  - The cytokines are a large and diverse family of polypeptide regulators with
      multiple regulatory functions that have been comprehensively evaluated in the
      immune system under strictly controlled experimental conditions. These peptide
      signals exhibit often unpredictable interactions when evaluated for their
      pathophysiological involvement in specific inflammatory conditions in vivo. In
      our joint efforts to understand the basis for early pathophysiological changes in
      the brains of HIV-infected subjects, we have developed animal models for
      lentivirus infections, and assessed the actions of various cytokines acutely on
      transmitter release properties in vitro, and in an in vivo transgenic mouse
      model. IL1beta, IL2, IL6, and IFNalpha will each enhance the release of AVP in
      slices of rat hypothalamus and amygdala. TGFbeta selectively blocks the ability
      of ACh to release AVP from hypothalamus or amygdala, but has no effects on the
      release stimulated by other cytokines. IFNalpha, but not TGFbeta will also
      activate CRH release; as with AVP, TGF selectively blocks the ACh-stimulated CRH
      release in both amygdala and hypothalamus. The IFNalpha-stimulated release of AVP
      and CRH appears to be mediated by cyclic GMP production, and this release by
      IFNalpha and IL-2 may be mediated in part by activation of constitutive nitric
      oxide synthase. These combined in vitro actions would suggest that cns cytokine
      actions should upregulate the hypothalamic pituitary adrenal axis. In a
      transgenic mouse model with increased astrocytic expression and release of the
      cytokine IL6, the HPA axis is upregulated, but the effect seems attributable to
      adrenocortical hypersensitization to ACTH. Lastly, in studies of cytokine
      mediated effects on astrocytic uptake of the excitatory transmitter glutamate,
      the reactive oxygen species hydrogen peroxide and peroxynitrite, but not nitric
      oxide, inhibited glutamate uptake in a concentration-dependent manner. Although
      superoxide and nitric oxide had no effect by themselves on the rate of glutamate
      uptake by astrocytes, the same cultures did respond to nitric oxide with a
      sustained increase in cytoplasmic free calcium. Thus while reactive oxygen
      species do provide a potential path to neurotoxicity but one apparently not
      involving nitric oxide. These various data provide important opportunities for
      early therapeutic interventions in neuro-inflammatory states such as Neuro-AIDS.

PMID- 9651549
TI  - Transgenic mice and cytokine actions in the brain: bridging the gap between
      structural and functional neuropathology.
AB  - Deciphering the neurobiological consequences of cerebral cytokine expression in
      vivo represents an important research objective which has implications for our
      understanding of the pathogenesis and treatment of many significant neurological
      disorders. In our own pursuit of this objective, studies by us have utilized a
      transgenic strategy employing the GFAP promoter to direct the chronic expression
      of the cytokines IL-3, IL-6, IFN-alpha or TNF-alpha to astrocytes in mice.
      Transgenic expression of each cytokine produces a unique spectrum of
      neuropathological and functional alterations, thereby directly implicating these
      mediators in the pathogenesis of CNS disease. Moreover, as exemplified here with
      the GFAP-IL6 transgenic mice, these models are valuable tools in which to perform
      multi-level analysis to link molecular and cellular alterations to specific
      electrophysiological, neuroendocrine and behavioral outcomes. Integrative studies
      such as described here in the GFAP-cytokine transgenic mice, are providing a more
      thorough understanding of the actions of cytokines in the CNS and bridge the gap
      between structural and functional neuropathology.

PMID- 9651550
TI  - Gene regulation of cell adhesion: a key step in neural morphogenesis.
AB  - A mounting body of evidence suggests that cell adhesion molecules (CAMs) play
      important roles in morphogenetic patterning of the nervous system. The combined
      factors that control the expression of CAMs during early neural development are,
      however, largely unknown. We have hypothesized that the coordinate expression of
      homeobox (Hox) and paired box (Pax) proteins in the neural axis leads to the
      differential expression of particular CAM genes. Following this hypothesis, we
      have characterized the promoters and identified cis-regulatory sequences that
      bind to and respond to Hox and Pax proteins in the genes for three neurally
      expressed CAMs - the neural cell adhesion molecule, N-CAM, the neuron-glia cell
      adhesion molecule, Ng-CAM, and L1. Experiments on transgenic mice carrying N-CAM
      promoter/lacZ reporter gene constructs indicated that mutation of either the HBS
      or the PBS disrupted patterning of N-CAM expression in the embryonic spinal cord.
      To examine the factors that restrict the expression of certain CAMs to the
      nervous system, we identified regulatory elements that block expression of the Ng
      CAM and L1 genes in non-neural cells. We characterized a 310 base pair region of
      the first intron of the Ng-CAM gene containing five neural restrictive silencer
      elements (NRSEs) and a binding site for the Pax-3 protein. These elements
      silenced activity of the Ng-CAM promoter in NIH3T3 fibroblasts, but had no effect
      on its activity in N2A neuroblastoma cells line. Similar analyses of the L1 gene
      revealed a single NRSE within the second intron that was important for silencing
      in this cellular transfection system. To analyze the role of the NRSE in vivo, we
      prepared transgenic mice containing two L1 gene/lacZ constructs, one containing
      the NRSE and another in which the NRSE was deleted. The wild type L1lacZ
      transgene showed a neurally restricted pattern of expression, whereas the NRSE
      mutated L1 construct showed extensive extraneural expression of the L1 gene.
      Thus, neural specificity of CAM expression is controlled by the NRSE. The general
      significance of these observations is that they connect the expression of
      important families of transcriptional regulators with gene products capable of
      direct cellular mechanochemistry.

PMID- 9651551
TI  - Long-term potentiation and spatial training are both associated with the
      generation of new excitatory synapses.

PMID- 9651553
TI  - How to study consciousness scientifically.

PMID- 9651552
TI  - Positive and negative regulatory mechanisms that mediate long-term memory
      storage.
AB  - The protein kinase A pathway and the cyclic AMP-response element binding protein
      (CREB) appear to play a critical role in the consolidation of short-term changes
      in neuronal activity into long-term memory storage in a variety of systems
      ranging from the gill and siphon withdrawal reflex in Aplysia to olfactory
      conditioning in Drosophila to spatial and contextual learning in mice. In this
      review we describe the molecular machinery that mediates memory consolidation in
      each of these systems. One of the surprising findings to emerge, particularly
      from studies of long-term facilitation in Aplysia, is that memory storage is
      mediated by not only positive but also negative regulatory mechanisms, in much
      the same way as cell division is controlled by the proteins encoded by oncogenes
      and tumor suppressor genes. This suggests the interesting possibility that there
      are memory suppressor genes whose protein products impede memory storage.

PMID- 9651554
TI  - Do genetic determinates of ischaemic heart disease imply that prevention may
      become more difficult?
AB  - Favourable changes in environment and lifestyle in the community may lead to a
      situation in which genetic determinants of ischaemic heart disease assume greater
      importance. Does this imply that ischaemic heart disease becomes more difficult
      to prevent? Much of the role of the family history as a risk factor within
      populations may be explained by new genetic mutations. However, differences
      between populations are generally attributable to environmental differences. A
      model of gene-environment interaction implies that individuals or populations
      with genetic risk markers are both more susceptible and more responsive to
      environmental changes, including lifestyle and drugs, and thus, may be eminently
      treatable.

PMID- 9651555
TI  - Metabolic features of inflammatory bowel disease in a remission phase of the
      disease activity.
AB  - OBJECTIVES: To evaluate the anthropometric and metabolic characteristics of
      patients with Crohn's disease (CD) and ulcerative colitis (UC), comparing both
      groups with healthy volunteers. DESIGN: A cross-sectional study. SETTING: The
      Department of Internal Medicine, Catholic University Hospital, Rome, Italy.
      SUBJECTS: Thirty-four patients with biopsy-proven inflammatory bowel disease (18
      CD; 16 UC) in clinical remission (SCDAI < 3 and Powell-Tuck index < 4) not
      receiving steroid therapy. INTERVENTIONS: All patients had a clinical
      examination. MAIN OUTCOME MEASURES: Blood indicators of inflammation and
      nutritional status. Body composition was assessed by both anthropometry and
      bioimpedance and metabolic variables were measured by indirect calorimetry over a
      60-90 min period. RESULTS: CD had a lower body weight than both controls (58.1
      kg, range 41.5-71.0 vs. 66.4 kg, range 57.0-76.0; P < 0.001) and UC) 58.1 kg,
      range 41.5-71.0 vs. 69.6 kg, range 50.5-94.0; (P < 0.001). Fat-free mass (FFM)
      did not differ between the groups, whilst fat mass was significantly lower in CD
      than in UC (P < 0.05) and controls (P < 0.001). Normalizing the basal metabolic
      rate by FFM, a higher value was found in CD compared with UC (143 kJ kg-1) d-(
      1), range 97.5-179 vs. 133 kJ kg-1 d-1, range 123-148; P < 0.05) and control
      subject 143 kj kg-1 d-1, range 97.5-179 vs. 134 kj kg-1 d-1, range 122-162; P <
      0.05). The nonprotein respiratory quotient was significantly lower in CD compared
      to UC 0.80, range 0.73-0.84 vs. 0.84, range 0.79-0.91; P < 0.01) and controls
      (0.80, range 0.73-0.84 vs. 0.83, range 0.81-0.87; P < 0.001), with a consequently
      higher lipid oxidation rate in CD. CONCLUSIONS: CD subjects showed a decreased
      fat mass and enhanced utilization of lipids compared with UC and controls. These
      data could be explained by the larger intestinal involvement and considered as a
      contribution to lipid tissue wasting in CD.

PMID- 9651556
TI  - Dynamic assessment of parathyroid function in acute malaria.
AB  - OBJECTIVES: To investigate the dynamic parathyroid response to rapidly induced,
      sustained hypocalcaemia in patients with acute malaria and in healthy volunteers.
      DESIGN: Serum intact parathormone (PTH) concentrations were measured on samples
      taken before and during a variable-rate tri-sodium citrate infusion designed to
      'clamp' the whole blood ionised calcium concentration 0.20 mmol L-1 below
      baseline for 120 min. SUBJECTS: Six Malaysian patients aged 17-42 years with
      acute malaria, four of whom were restudied in convalescence, and 12 healthy
      controls aged 19-36 years. MAIN OUTCOME MEASURES: Whole-blood ionised calcium and
      serum intact PTH concentrations. RESULTS: The mean (SD baseline ionised calcium
      was lower in the malaria patients than in controls (1.09 +/- 0.06 vs. 1.18 +/-
      0.03 mmol L-1, respectively; P = 0.01) but PTH concentrations were similar (3.0
      +/- 1.8 vs. 3.3 +/- 1.3 pmol L(-1); P = 0.33). Target whole-blood ionised calcium
      concentrations were achieved more rapidly in the controls than the patients
      (within 15 vs. 30 min) despite significantly more citrate being required in the
      patients (area under the citrate infusion-time curve 0.95 (0.25 vs. 0.57 +/- 0.09
      mmol kg-1; P < 0.01). The ratio of the change in serum PTH to that in ionised
      calcium (delta PTH/ delta Ca2+), calculated to adjust for differences in initial
      rate of fall of ionised calcium, was similar during the first 5 min of the clamp
      (132 +/- 75 x 10(-6) vs. 131 +/- 43 x 10(-6) in patients and controls,
      respectively, P > 0.05), as were steady-state serum PTH levels during the second
      hour (7.0 +/- 2.2 pmol L-1 in each case). Convalescent patients had normal basal
      ionised calcium levels but the lowest serum intact PTH levels before and during
      the clamp, consistent with an increase in skeletal PTH sensitivity after
      treatment. CONCLUSIONS: There is a decreased ionised calcium 'set point' for
      basal PTH secretion but a normal PTH response to acute hypocalcaemia in malaria.
      Skeletal resistance may attenuate the effects of the PTH response but patients
      with malaria appear relatively resistant to the calcium chelating effects of
      citrated blood products.

PMID- 9651557
TI  - Gemfibrozil decreases autoantibodies against oxidized low-density lipoprotein in
      men with combined hyperlipidaemia.
AB  - OBJECTIVES: Gemfibrozil is the most widely used fibric acid for the management of
      combined hyperlipidaemia. It has beneficial effects in the prevention of coronary
      heart disease (CHD). The mechanisms by which it exerts this effect are not
      completely resolved. We studied whether gemfibrozil affects low-density
      lipoprotein (LDL) size and LDL oxidation parameters in males with a moderate
      combined hyperlipidaemia at high risk for progressive atherosclerosis. DESIGN:
      Open treatment with 2 x 600 mg gemfibrozil daily for 12 weeks. SETTING:
      Outpatient lipid clinic of a tertiary referral centre. SUBJECTS: Twenty-three
      patients with combined hyperlipidaemia and CHD or a positive family history for
      both CHD and hyperlipidaemia. MAIN OUTCOME MEASURES: Effects on triglyceride
      (TG), autoantibodies to oxidized LDL, LDL pattern and resistance to oxidative
      modification. RESULTS: During treatment with gemfibrozil, plasma TG concentration
      decreased from 2.83 +/- 0.85 to 2.02 +/- 0.89 mmol L-1 (P < 0.001). All but one
      patient were shown to have LDL pattern B. The LDL pattern did not change upon
      treatment with gemfibrozil. The resistance to oxidation, reflected in the lagtime
      during in-vitro oxidation slightly decreased from 105 +/- 22 to 99 +/- 18 min (P
      = 0.01). The concentration of autoantibodies against oxidized LDL indicates the
      rate of LDL oxidation in vivo. This concentration significantly decreased from
      14.2 +/- 9.9 to 13.1 +/- 9.2 mg L-1 (P < 0.01). CONCLUSIONS: The beneficial
      effect of gemfibrozil in reducing CHD may at least in part depend on a decrease
      of the rate of LDL oxidation in vivo.

PMID- 9651558
TI  - Salbutamol inhalation has no effect on myocardial ischaemia, arrhythmias and
      heart-rate variability in patients with coronary artery disease plus asthma or
      chronic obstructive pulmonary disease.
AB  - OBJECTIVES: Inhaled beta-2 agonists raise heart rate, systolic blood pressure and
      contractility, all of which cause an increase in oxygen consumption of the heart.
      We performed a study on the influence of inhaled salbutamol on myocardial
      ischaemia, rhythm, and heart rate variability as assessed by Holter monitoring of
      24 patients with coronary artery disease (CAD) and clinically stable asthma or
      chronic obstructive pulmonary disease (COPD). DESIGN: In hospital the patients
      received 0.2 mg (hour 1), 0.4 mg (hour 6), 0.8 mg (hour 13) of salbutamol with a
      metered-dose inhaler and a spacer, and 5 mg (hour 25) with a nebulizer; symptoms,
      peak expiratory flow (PEF), 30-h Holter monitoring, and blood pressure (BP) were
      recorded. The study parameters were compared for the hour preceding and following
      each dose of salbutamol. RESULTS: No cardiac symptoms were associated with
      salbutamol inhalation. PEF increased after all doses (P < 0.005). A dose of 0.2
      mg salbutamol induced no changes in heart rate, whereas dose of 0.4 mg increased
      heart rate from a mean of 75 +/- 13 to 79 +/- 14 beats min-1 (P < 0.005), and a
      dose of 0.8 mg from 76 +/- 14 to 78 +/- 15 beats min-1 (P < 0.05). No changes in
      systolic BP appeared after any dose of salbutamol. The diastolic BP was lowered
      after 0.8 mg of salbutamol from 86 +/- 12 to 82 +/- 10 mmHg (P < 0.05). The 5 mg
      of nebulized drug provoked no significant changes in heart rate or BP. Myocardial
      ischaemia, heart rate variability and ventricular arrhythmias remained unaltered
      with all doses. CONCLUSIONS: The commonly used doses of inhaled or nebulized
      salbutamol induced no acute myocardial ischaemia, arrhythmias or changes in heart
      rate variability in patients with CAD and clinically stable asthma or COPD.

PMID- 9651559
TI  - Efficacy and safety of systemic recombinant interferon-alpha in Behcet's disease.
AB  - OBJECTIVES: To evaluate the therapeutic efficacy and safety of systemic
      recombinant interferon alpha-2a (IFN-alpha) in patients with Behcet's disease
      (BD) and to determine the incidence of episodes in complete responders during the
      one-year pretreatment period and follow-up. DESIGN: An open clinical study.
      SETTING: Departments of Dermatology and Ophthalmology, University of Patras,
      Greece and Department of Dermatology, Heinrich-Heine University of Dusseldorf,
      Germany. SUBJECTS: Twelve patients (aged 23-52 years) with active BD who had
      previously been unsuccessfully treated with systemic steroids and/or
      immunosuppressives. INTERVENTIONS: IFN-alpha was administered subcutaneously at a
      dose of 6 X 10(6) IU per day 3 times per week for 2 months. MAIN OUTCOME
      MEASURES: Change of area or number of mucocutaneous lesions, grading score for
      thrombophlebitis and ocular inflammation, haematological and biochemical
      parameters and number of episodes during the pretreatment period and the follow
      up. Evaluation of IFN-alpha side effects. RESULTS: Nine patients (75.0%) revealed
      a complete remission, two (16.6%) a partial remission and one patient (8.3%)
      showed no response. During the follow-up in five out of the nine complete
      responders (55.5%) no episodes of BD were seen, whereas, the other four patients
      (44.5%) had 1-2 episodes, as compared to 5-8 and 5-12 episodes, respectively,
      during the pretreatment period. An influenza-like syndrome (fever, nausea and
      myalgias) appeared during the early phase of therapy in all (but one) patients.
      No patient had to discontinue IFN-alpha because of intolerance. CONCLUSIONS:
      Subcutaneous human recombinant interferon alpha-2a appears to be an effective and
      fairly well tolerated therapy for BD.

PMID- 9651560
TI  - Compliance with and efficacy of treatment with pravastatin and cholestyramine: a
      randomized study on lipid-lowering in primary care.
AB  - OBJECTIVES: Lipid-lowering drugs as 3-hydroxy-3-methyl glutaryl coenzyme A (HMG
      CoA) reductase inhibitors and cholestyramine are effective in reducing
      cardiovascular morbidity both in primary and secondary prevention. Patient
      compliance is an important determinant of the outcome of therapy. This study was
      designed to compare compliance with tolerance and lipid-lowering effectiveness of
      pravastatin and/or cholestyramine in primary care. DESIGN: Nine hundred and
      eighty nine women and 1047 men were randomized to treatment at 100 primary-care
      centres in Sweden. After dietary intervention, an eligible patient was randomly
      assigned to one of four programs of daily treatment: group Q, 16 g
      cholestyramine, group QP, 8 g cholestyramine and 20 mg pravastatin, group P20, 20
      mg pravastatin or group P40, 40 mg pravastatin. RESULTS: In group Q, group QP,
      group P20 and group P40 the reductions in low density lipoprotein (LDL)
      cholesterol were 26%, 36%, 27% and 32%. The dose actually taken was 91-95% of the
      prescribed for the pravastatin treatment groups and 77-88% for the cholestyramine
      groups. In the pravastatin and cholestyramine groups 76-78% and 44-53%,
      respectively, completed the trial. Only 8-27% of the patients reached a serum
      cholesterol target level of 5.2 mmol L-1. There was no difference in lipid
      lowering effect between women and men. CONCLUSION: Pravastatin alone is
      efficacious and compliance is high, independent of dose. Combined treatment with
      cholestyramine and pravastatin had a better cholesterol lowering effect (although
      not statistically significant) than 40 mg pravastatin. Despite this, only 8-27%
      of the patients actually reached a serum cholesterol level of 5.2 mmol L-1. No
      unexpected serious adverse events were detected in any of the treatment groups.
      As predicted, the gastrointestinal disturbances were more common on
      cholestyramine treatment. These two factors suggest that an increase in the
      dosage of the HMG-CoA reductase inhibitor may be appropriate. Results from other
      studies indicate that there also might be other positive effects of statin
      treatment beyond cholesterol lowering.

PMID- 9651561
TI  - Serum 25-hydroxyvitamin D levels and bone mineral density in 16-20 years-old
      girls: lack of association.
AB  - OBJECTIVE: Hypovitaminosis D has been shown to be associated with low bone
      mineral density in middle-aged and elderly women. The aim of this study was to
      evaluate whether such an association might exist in adolescent and young adult
      girls, approaching peak bone mass. DESIGN: Cross-sectional study carried out in
      late winter. SETTING: Reykjavik area at latitude 64 degrees N. SUBJECTS: Two
      hundred and fifty-nine Icelandic Caucasian girls, aged 16, 18 and 20 years,
      randomly selected from the registry of Reykjavik. MAIN OUTCOME MEASURES: Bone
      mineral density in lumbar spine, hip, distal forearm and total skeleton was
      measured with dual-energy X-ray absorptiometry (DEXA) and compared with 25
      hydroxyvitamin D levels [25 (OH)D] in serum, measured by radioimmunoassay.
      Calcium and vitamin-D intake were also assessed by a questionnaire. RESULTS:
      18.5% of the girls were below 25 nmol L-1 in serum 25 (OH)D which has been
      recognized as the lower normal limit for adults. No significant association was
      found between 25 (OH)D levels and bone mineral density. CONCLUSIONS: Normal
      calcium and phosphate concentrations in plasma and normal bone mineral density
      are maintained in adolescent and young adult girls at lower 25 (OH)D levels than
      published 'normal' levels for middle-aged and elderly.

PMID- 9651562
TI  - Hypoglycaemia following pancreatic allograft transplantation.
AB  - Pancreatic transplantation is an established treatment for patients with insulin
      dependent diabetes mellitus. Side-effects are mainly related to surgical
      complications, immunosuppressive therapy and graft rejection. We report on two
      patients having recurrent hypoglycaemic events following pancreatic
      transplantation. The cause of hypoglycaemia in our patients remained obscure.
      Hypoglycaemia following pancreatic transplantation has been described.
      Hypoglycaemic events may appear years after transplantation. In the article we
      review three possible mechanisms of hypoglycaemia: hyperinsulinaemia, secondary
      to systemic drainage (due to loss of first pass hepatic insulin clearance),
      presence of anti-insulin antibodies and persistence of counter-regulatory
      abnormalities. Physicians and patients should be aware of possible hypoglycaemia
      events following transplantation.

PMID- 9651563
TI  - Atherosclerosis: usage and misusage.

PMID- 9651565
TI  - Cardiac tamponade preceding adrenal insufficiency--an unusual presentation of
      Addison's disease.

PMID- 9651564
TI  - Hyperthyroidism and pulmonary hypertension.

PMID- 9651566
TI  - Neurobiology of the association of chronic work stress with atherogenic lipids
      and elevated fibrinogen in middle-aged men.

PMID- 9651567
TI  - Smoking cessation in patients with stable or unstable ischaemic heart disease.

PMID- 9651568
TI  - The additional effects of acipimox to simvastatin in the treatment of combined
      hyperlipidaemia.
AB  - OBJECTIVES: Nicotinic acid, an effective drug for treatment of combined
      hyperlipidaemia, is often not tolerated because of side-effects. Acipimox is a
      nicotinic acid like lipid lowering drug with less side-effects. We studied
      whether the addition of acipimox to simvastatin improves the lipid profile in
      patients with a combined hyperlipidaemia. DESIGN: Randomized double-blind placebo
      controlled crossover trial. SETTING: Outpatient lipid clinic of a tertiary
      referral centre. SUBJECTS: Eighteen patients with combined hyperlipidaemia
      treated with diet and 20-40 mg simvastatin for at least 3 months. INTERVENTION:
      Acipimox in a daily dose of 3 X 250 mg for 12 weeks. MAIN OUTCOME MEASURES:
      Effects on the concentration of LDLc, TG, HDLc, Lp(a) and Apolipoprotein B, as
      well as on LDL-size and LDL-resistance to oxidative modification. RESULTS:
      Acipimox reduced Lp(a) levels by 8% (P < 0.05). A substantial but not
      statistically significant change in TG (-32%) and HDLc (+6%) levels was seen. All
      patients were found to have small dense LDL, with a size of 229 +/- 4 A. LDL size
      and the resistance to oxidation, reflected in the lag phase during in vitro
      oxidation, were not affected by the addition of acipimox. In a subgroup of 8
      patients with the most severe hypertriglyceridaemia (baseline TG > 4 mmol L-
      [1]), acipimox induced a significant increase in HDLc (+ 15%, P < 0.01). The
      effects on TG (-41%), LDLc (-10%) and lag phase (+17%) were also more pronounced
      than in the group with a lower baseline TG, but none of these changes reached the
      level of significance. CONCLUSIONS: Adding acipimox to simvastatin reduced Lp(a)
      and substantially but not significantly lowered TG. However, in patients with the
      highest TG levels. HDLc was also significantly improved.

PMID- 9651569
TI  - [Treatment costs in a medical intensive care unit: a comparison of 1992 and
      1997].
AB  - BACKGROUND AND OBJECTIVE: Treatment in an intensive care unit (ICU) is very
      expensive. Aim of this study was to determine the exact composition of costs and
      to analyse what factors are responsible for the rise in costs over the last 5
      years. METHODS: In a prospective investigation all 790 patients who had been
      treated at the ICU of the Medical Department of Frankfurt University during 1992
      were included, findings being compared with data on all 208 patients treated in
      the ICU in May and June 1997. All important diagnostic and therapeutic measures
      were quantitatively determined each day. RESULTS: The mean age of the ICU
      patients rose in the 5 years from 55 to 59 years (P < 0.001). Mean period of stay
      in the ICU remained unchanged (4.1 days), total duration of hospital stay (15 and
      12 days, respectively), and treatment intensity (sum of points according to the
      "Therapeutic Intervention Scoring System" per ICU stay: 96 and 77, respectively).
      The mortality rate in the ICU fell from 16.3% to 10.6% (P = 0.02), hospital
      mortality rate from 23% to 14% (P = 0.01). Total cost rose from DM 797,860 to DM
      1,148,945 per 100 patients (+44%). Of this total, personnel costs were DM 286,885
      in 1992 and 356,091 in 1997 (+24%), costs for apparatus-based diagnostic and
      therapeutic tests were DM 169,743 and 245,156, respectively (+44%), DM 98,496 and
      129,222 for drugs (+31%), and DM 60,399 and 186,671 (+209%) for blood and
      clotting products (in each category per 100 patients). Per case costs rose from
      DM 7970 to 11,489, per day costs from DM 1943 to 2831. 90% of cost increases were
      due to new strategies in the treatment of patients with myocardial infractions
      and those with severe clotting disorders and a rise in personnel costs.
      CONCLUSION: The costs of a stay in the ICU has greatly increased over the last 5
      years, the main causes being a change to new forms of treatment, especially in
      patients with myocardial infarction and those with haemophilia.

PMID- 9651570
TI  - [Percutaneous balloon pericardiotomy for the treatment of a malignant pericardial
      tamponade].
AB  - HISTORY AND CLINICAL FINDINGS: A 72-year old man was admitted because of
      increasing dyspnoea, failing fitness and weight loss. Physical examination was
      unremarkable except for decreased heart sounds. INVESTIGATIONS: He was anaemic
      (haemoglobin 11.7 g/dl), erythrocyte sedimentation rate was raised (80/90 mm) as
      was C-reactive protein (169 mg/dl). Chest radiogram showed tent-like widening of
      the cardiac silhouette and a 6 cm space-occupying lesion in the left hilus.
      Echocardiography revealed pericardial effusion of up to 2.3 cm (epi- to
      pericardium). TREATMENT AND COURSE: Because of an increase in dyspnoea and
      pericardial effusion a pericardiocentesis was performed. This fluid and needle
      biopsy of the space-occupying lesion revealed small-cell carcinoma. 6 days after
      the pericardiocentesis the dyspnoea further increased as did the pericardial
      effusion (to 3.9 cm). Percutaneous balloon pericardiotomy was uneventfully
      performed. During a follow-up period of 14 months there were no further
      pericardial effusions. CONCLUSION: Percutaneous balloon pericardiotomy can be
      undertaken as a minimally invasive treatment of symptomatic pericardial effusion.
      It should be considered as an alternative to surgical creation of a pericardial
      window, especially in very ill patients.

PMID- 9651571
TI  - [Primary pulmonary plasmacytoma. Case report of a rare lung tumor].
AB  - HISTORY AND CLINICAL FINDINGS: A 45-year old man, suffering from dry cough
      without haemoptysis, was admitted for evaluation of pulmonary changes of
      uncertain aetiology. A chest radiograph and computed tomography (CT) had shown a
      large space-occupying lesion in the left hilus. His general condition was poor
      and he had resting dyspnoea and stridor. On auscultation of the lung there were
      decreased breath sounds and dry rales over the left and vesicular breathing over
      the right lung. INVESTIGATIONS: CT revealed a 7.0 x 6.0 cm space-occupying lesion
      in the left hilus and ipsilaterally a tumour in the dorsolateral lower lobe
      surrounding the left lower lobe bronchus. Initial bronchoscopy showed this
      bronchus to be involved in the tumour process. Biopsy demonstrated monomorphic
      proliferating plasma cells which on immunochemical testing showed selective
      staining to lambda-light chains and immunoglobulin G. The first serum
      electrophoresis was unremarkable, but a later repeat discovered a small amount of
      paraprotein for IgG-lambda type. Bence-Jones protein was demonstrated in the
      urine. On the basis of these findings an extramedullary plasmacytoma of the lung
      (PPP) was diagnosed. TREATMENT AND COURSE: At first the patient was given i.v.
      chemotherapy, and to prevent a threatening bronchial occlusion oral dexamethasone
      was given. Pericardial effusion and recurrent retention pneumonia developed. 6
      month after onset of symptoms radiotherapy was begun and the tumour became
      markedly smaller. CONCLUSION: PPP should be included in the differential
      diagnosis of pulmonary space-occupying lesions even when initial serum protein
      electrophoresis is negative for monoclonal paraproteinaemia. Pericardial effusion
      may be caused by pulmonary involvement of the plasma cell tumours.

PMID- 9651572
TI  - [Angioedema caused by C1 esterase inhibitor deficiency].

PMID- 9651573
TI  - [Social medicine evaluation and advice for patients with coronary heart disease].

PMID- 9651574
TI  - [Anticardiolipin antibody level in myocardial infarction].

PMID- 9651576
TI  - [Physical training in geriatrics].

PMID- 9651575
TI  - ["Auto-continuous positive airway pressure" and "autotitration"].

PMID- 9651577
TI  - The CRY1 blue light photoreceptor of Arabidopsis interacts with phytochrome A in
      vitro.
AB  - Plants have at least two major photosensory receptors: phytochrome (absorbing
      primarily red/far-red light) and cryptochrome (absorbing blue/UV-A light);
      considerable physiological and genetic evidence suggests some form of
      communication or functional dependence between the receptors. Here, we
      demonstrate in vitro, using purified recombinant photoreceptors, that Arabidopsis
      CRY1 and CRY2 (cryptochrome) are substrates for phosphorylation by a phytochrome
      A-associated kinase activity. Several mutations within the CRY1 C terminus lead
      to reduced phosphorylation by phytochrome preparations in vitro. Yeast two-hybrid
      interaction studies using expressed C-terminal fragments of CRY1 and phytochrome
      A from Arabidopsis confirm a direct physical interaction between both
      photoreceptors. In vivo labeling studies and specific mutant alleles of CRY1,
      which interfere with the function of phytochrome, suggest the possible relevance
      of these findings in vivo.

PMID- 9651578
TI  - Autoactivation of procaspase-9 by Apaf-1-mediated oligomerization.
AB  - Activation of procaspase-9 by Apaf-1 in the cytochrome c/dATP-dependent pathway
      requires proteolytic cleavage to generate the mature caspase molecule. To
      elucidate the mechanism of activation of procaspase-9 by Apaf-1, we designed an
      in vitro Apaf-1-procaspase-9 activation system using recombinant components.
      Here, we show that deletion of the Apaf-1 WD-40 repeats makes Apaf-1
      constitutively active and capable of processing procaspase-9 independent of
      cytochrome c an dATP. Apaf-1-mediated processing of procaspase-9 occurs at Asp
      315 by an intrinsic autocatalytic activity of procaspase-9 itself. We provide
      evidence that Apaf-1 can form oligomers and may facilitate procaspase-9
      autoactivation by oligomerizing its precursor molecules. Once activated, caspase
      9 can initiate a caspase cascade involving the downstream executioners caspase-3,
      -6, and -7.

PMID- 9651579
TI  - The von Hippel-Lindau tumor suppressor protein is required for proper assembly of
      an extracellular fibronectin matrix.
AB  - Fibronectin coimmunoprecipitated with wild-type von Hippel-Lindau protein (pVHL)
      but not tumor-derived pVHL mutants. Immunofluorescence and biochemical
      fractionation experiments showed that fibronectin colocalized with a fraction of
      pVHL associated with the endoplasmic reticulum, and cold competition experiments
      suggested that complexes between fibronectin and pVHL exist in intact cells.
      Assembly of an extracellular fibronectin matrix by VHL-/- renal carcinoma cells,
      as determined by immunofluorescence and ELISA assays, was grossly defective
      compared with VHL+/+ renal carcinoma cells. Reintroduction of wildtype, but not
      mutant, pVHL into VHL-/- renal carcinoma cells partially corrected this defect.
      Finally, extracellular fibronectin matrix assembly by VHL-/- mouse embryos and
      mouse embryo fibroblasts (MEFs), unlike their VHL+/+ counterparts, was grossly
      impaired. These data support a direct role of pVHL in fibronectin matrix
      assembly.

PMID- 9651580
TI  - The 3' to 5' exonuclease activity of Mre 11 facilitates repair of DNA double
      strand breaks.
AB  - MRE11 and RAD50 are known to be required for nonhomologous joining of DNA ends in
      vivo. We have investigated the enzymatic activities of the purified proteins and
      found that Mre11 by itself has 3' to 5' exonuclease activity that is increased
      when Mre11 is in a complex with Rad50. Mre11 also exhibits endonuclease activity,
      as shown by the asymmetric opening of DNA hairpin loops. In conjunction with a
      DNA ligase, Mre11 promotes the joining of noncomplementary ends in vitro by
      utilizing short homologies near the ends of the DNA fragments. Sequence
      identities of 1-5 base pairs are present at all of these junctions, and their
      diversity is consistent with the products of nonhomologous end-joining observed
      in vivo.

PMID- 9651581
TI  - A mouse model for the basal transcription/DNA repair syndrome
      trichothiodystrophy.
AB  - The sun-sensitive form of the severe neurodevelopmental, brittle hair disorder
      trichothiodystrophy (TTD) is caused by point mutations in the essential XPB and
      XPD helicase subunits of the dual functional DNA repair/basal transcription
      factor TFIIH. The phenotype is hypothesized to be in part derived from a
      nucleotide excision repair defect and in part from a subtle basal transcription
      deficiency accounting for the nonrepair TTD features. Using a novel gene
      targeting strategy, we have mimicked the causative XPD point mutation of a TTD
      patient in the mouse. TTD mice reflect to a remarkable extent the human disorder,
      including brittle hair, developmental abnormalities, reduced life span, UV
      sensitivity, and skin abnormalities. The cutaneous symptoms are associated with
      reduced transcription of a skin-specific gene strongly supporting the concept of
      TTD as a human disease due to inborn defects in basal transcription and DNA
      repair.

PMID- 9651582
TI  - Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF
      and inhibits 3'end formation of cellular pre-mRNAs.
AB  - Inhibition of the nuclear export of poly(A)-containing mRNAs caused by the
      influenza A virus NS1 protein requires its effector domain. Here, we demonstrate
      that the NS1 effector domain functionally interacts with the cellular 30 kDa
      subunit of CPSF, an essential component of the 3' end processing machinery of
      cellular pre-mRNAs. In influenza virus-infected cells, the NS1 protein is
      physically associated with CPSF 30 kDa. Binding of the NS1 protein to the 30 kDa
      protein in vitro prevents CPSF binding to the RNA substrate and inhibits 3' end
      cleavage and polyadenylation of host pre-mRNAs. The NS1 protein also inhibits 3'
      end processing in vivo, and the uncleaved pre-mRNA remains in the nucleus. Via
      this novel regulation of pre-mRNA 3' end processing, the NS1 protein selectively
      inhibits the nuclear export of cellular, and not viral, mRNAs.

PMID- 9651583
TI  - Coordinated leading and lagging strand DNA synthesis on a minicircular template.
AB  - The coordinated synthesis of both leading and lagging DNA strands is thought to
      involve a dimeric DNA polymerase and a looping of the lagging strand so that both
      strands can be synthesized in the same direction. We have constructed a
      minicircle with a replication fork that permits an assessment of the
      stoichiometry of the proteins and a measurement of the synthesis of each strand.
      The replisome consisting of bacteriophage T7 DNA polymerase, helicase, primase,
      and single-stranded DNA-binding protein mediates coordinated replication. The
      criteria for coordination are fulfilled: (1) a replication loop is formed, (2)
      leading and lagging strand synthesis are coupled, (3) the lagging strand
      polymerase recycles from one Okazaki fragment to another, and (4) the length of
      Okazaki fragments is regulated. T7 single-stranded DNA-binding protein is
      essential for coordination.

PMID- 9651584
TI  - Assembly of a 12/23 paired signal complex: a critical control point in V(D)J
      recombination.
AB  - The 12/23 rule requires that V(D)J recombination only occurs between
      recombination signals with 12 and 23 base pair spacers. We show that the 12/23
      rule is established prior to DNA cleavage, by the formation of a synaptic complex
      containing both 12-spacer and 23-spacer signals. The RAG1 and RAG2 proteins, as
      well as the DNA bending protein HMG1, are needed for efficient formation of this
      complex. We show further that the synaptic complex is the functional complex for
      coupled cleavage. After cleavage, all four broken DNA ends remain associated with
      the RAG proteins in a postcleavage synaptic complex, whose existence helps to
      explain the known role of RAG1 and RAG2 in the subsequent end-joining events that
      complete V(D)J recombination.

PMID- 9651585
TI  - SAP30, a novel protein conserved between human and yeast, is a component of a
      histone deacetylase complex.
AB  - Histone acetylation plays a key role in the regulation of eukaryotic gene
      expression. Recently, histone acetylation and deacetylation were found to be
      catalyzed by structurally distinct, multisubunit complexes that mediate,
      respectively, activation and repression of transcription. Here, we identify SAP30
      as a novel component of the human histone deacetylase complex that includes Sin3,
      the histone deacetylases HDAC1 and HDAC2, histone binding proteins RbAp46 and
      RbAp48, as well as other polypeptides. Moreover, we describe a SAP30 homolog in
      yeast that is functionally related to Sin3 and the histone deacetylase Rpd3. The
      human SAP30 complex is active in deacetylating core histone octamers, but
      inactive in deacetylating nucleosomal histones due to the inability of the
      histone binding proteins RbAp46 and RbAp48 to gain access to nucleosomal
      histones. These results define SAP30 as a component of a histone deacetylase
      complex conserved among eukaryotic organisms.

PMID- 9651586
TI  - Transcriptional pausing at +62 of the HIV-1 nascent RNA modulates formation of
      the TAR RNA structure.
AB  - A strong transcriptional pause delays human RNA polymerase II three nt after the
      last potentially paired base in HIV-1 TAR, the RNA structure that binds the
      transactivator protein Tat. We report here that the HIV-1 pause depends in part
      on an alternative RNA structure (the HIV-1 pause hairpin) that competes with
      formation of TAR. By probing the nascent RNA structure in halted transcription
      complexes, we found that the transcript folds as the pause hairpin before and at
      the pause, and rearranges to TAR concurrent with or just after escape from the
      pause. The pause signal triggers a 2 nt reverse translocation by RNA polymerase
      that may block the active site and be counteracted by formation of TAR. Thus, the
      HIV-1 pause site modulates nascent RNA rearrangement from a structure that favors
      pausing to one that both recruits Tat and promotes escape from the pause.

PMID- 9651587
TI  - Conditional loss-of-myosin-II-function mutants reveal a position in the tail that
      is critical for filament nucleation.
AB  - Myosin-II must be assembled into filaments to perform its cellular functions. Two
      conditional loss-of-myosin-II-function mutants were recovered from a previous
      genetic screen with defects that were mapped to the coiled-coil tail region of
      Dictyostelium myosin-II. Strikingly, both tail mutations affected the same
      arginine residue at position 1880. A single amino acid substitution, R1880P,
      disrupted both the dimerization and tetramerization steps of filament nucleation.
      Even a single charge reversal at this position, R1880D, was sufficient to inhibit
      filament assembly, while other single charge reversals in the region of
      antiparallel contract suppressed these filament assembly mutants. The
      considerable impact of small electrostatic forces on nucleation suggests that
      these steps are delicately balanced and easily reversible.

PMID- 9651588
TI  - A single amino acid change in the yeast retrotransposon Ty5 abolishes targeting
      to silent chromatin.
AB  - Many retrotransposons and retroviruses are thought to select integration sites
      through interactions with specific chromosomal proteins. In yeast, the Ty5
      retrotransposon integrates preferentially with regions bound by silent chromatin,
      namely the telomeres and the HMR and HML mating loci. A Ty5 mutant (M3) was
      identified with an approximately 20-fold decrease in targeted integration as
      measured by a plasmid-based targeting assay. Often chromosomal insertions
      generated by M3, none were located at the telomeres or silent mating loci. A
      single amino acid change at the boundary of integrase and reverse transcriptase
      is responsible for the mutant phenotype. We predict that this mutation lies
      within a targeting domain that mediates Ty5 target choice by interacting with a
      component of silent chromatin.

PMID- 9651589
TI  - The Drosophila Polycomb group gene pleiohomeotic encodes a DNA binding protein
      with homology to the transcription factor YY1.
AB  - Genes of the Polycomb group (PcG) of Drosophila encode proteins necessary for the
      maintenance of transcriptional repression of homeotic genes. PcG proteins are
      thought to act by binding as multiprotein complexes to DNA through Polycomb group
      response elements (PREs); however, specific DNA binding has not been demonstrated
      for any of the PcG proteins. We have identified a sequence-specific DNA binding
      protein that interacts with a PRE from the Drosophila engrailed gene. This
      protein (PHO) is a homolog of the ubiquitous mammalian transcription factor Yin
      Yang-1 and is encoded by pleiohomeotic, a known member of the PcG. We propose
      that PHO acts to anchor PcG protein complexes to DNA.

PMID- 9651590
TI  - A conserved sequence motif in Polycomb-response elements.

PMID- 9651591
TI  - Intravascular imaging.
AB  - Based on three-dimensional (3D) information, quantitative data such as plaque
      volume can be calculated. The procedure includes automatic contour detection
      based in image segmentation methods and greatly speeds up clinical evaluation.
      With the use of additional X-ray information, the true tortuous vessel geometry
      can be reconstructed in 3D. This allows, by numerical modelling techniques, to
      calculate endothelial shear stress values which in turn may indicate sites prone
      to stenosis. With a decorrelation technique for radio frequency (RF) echo
      information from sequential data in the same beam direction and integration
      method over the entire cross section, blood velocity can be shown colour-coded
      during the cardiac cycle, while even blood flow quantification seems to be
      possible. In vitro as well as animal experiments have shown the feasibility of
      the method. Intravascular imaging can be used to study the biomechanical
      properties of atheroma components. Local radial strain as a measure of local
      tissue hardness can be estimated in principle. Hard or soft plaques can be
      identified from the strain images independently of the echogenic contrast between
      plaque and vessel wall.

PMID- 9651592
TI  - Three-dimensional ultrasound imaging of the vasculature.
AB  - With conventional ultrasonography, the diagnostician must view a series of two
      dimensional images in order to form a mental impression of the three-dimensional
      anatomy, an efficient and time consuming practice prone to operator variability,
      which may cause variable or even incorrect diagnoses. Also, a conventional two
      dimensional ultrasound image represents a thin slice of the patients anatomy at a
      single location and orientation, which is difficult to reproduce at a later time.
      These factors make conventional ultrasonography non-optimal for prospective or
      follow-up studies. Our efforts have focused on overcoming these deficiencies by
      developing three-dimensional ultrasound imaging techniques that are capable of
      acquiring B-mode, colour Doppler and power Doppler images of the vasculature, by
      using a conventional ultrasound system to acquire a series of two-dimensional
      images and then mathematically reconstructing them into a single three
      dimensional image, which may then be viewed interactively on an inexpensive
      desktop computer. We report here on two approaches: (1) free-hand scanning, in
      which a magnetic positioning device is attached to the ultrasound transducer to
      record the position and orientation of each two-dimensional image needed for the
      three-dimensional image reconstruction; and (2) mechanical scanning, in which a
      motor-driven assembly is used to translate the transducer linearly across the
      neck, yielding a set of uniformly-spaced parallel two-dimensional images.

PMID- 9651593
TI  - Edge detection in prostatic ultrasound images using integrated edge maps.
AB  - OBJECTIVE: We investigated an algorithm to detect grey level transitions with
      multiple scales of resolution to improve edge detection and localisation in
      ultrasound images of the prostate. INTRODUCTION: We had developed a non
      analytical operator for prostate contour determination implemented with minimum
      and maximum filters and locate edges. We implemented a technique for improved
      determination of boundary parts in prostatic ultrasound images by adjusting the
      edge detection parameter to signal information. METHODS: First the influence of
      prefilter settings and edge detection parameters is investigated in a test image
      and a real ultrasound image. Then, local standard deviation is used to identify
      or fewer homogeneous regions that are filtered with course resolution, while
      areas with larger deviation that grey level transitions occur, which should be
      preserved using smaller filter sizes to improve edge localisation. RESULTS:
      Analysis of images with different filter sizes indicated that areas are merged
      for increasing filter sizes: less pronounced edges disappear or displace for
      larger filters. Two scales of resolution lead to an improved localisation of
      edges when smaller filter sizes are used in areas with an increased local
      standard deviation. CONCLUSIONS: This paper illustrates an edge detection method
      suitable as pre-processing step in interpretation of medical images. By adapting
      input parameters to signal information, object recognition can be applied in
      images from different imaging modalities. Also, disadvantages are discussed,
      resulting in a new application combining a localisation algorithm to find the
      initial contour and a delineation algorithm to improve the outlining of the
      resulting contour.

PMID- 9651594
TI  - Real-time sonomammography based on the intersecting canonical body approximation
      of the diffracted wave field.
AB  - The inverse problem of the identification of an anomalous object (e.g., cyst or
      tumor) in a female breast immersed in water is solved by the matching of
      theoretical fields (for trial objects), employing an approximate field ansatz, to
      the scattered ultrasonic wave field measured on a surface fully enclosing the
      object.

PMID- 9651596
TI  - Quality assurance tools for therapeutic ultrasound.
AB  - Compared to diagnostic ultrasound, special phantoms and measurement techniques
      for therapeutic ultrasound are still far from standardization. In the following
      article, the development of quality assurance (QA) tools for two therapy methods
      are described: Extracorporeal shockwave lithotripsy (ESWL) and high intensity
      focused ultrasound (HiFU). The three consequent parts are QA tools in research
      and development, QA in clinical environment and standardization. For part one the
      computerized scanning with hydrophones, the use of Schlieren optics and sound
      force balances are state of the art. For clinical use the test procedures have to
      be simple so that routine checking of the equipment becomes convenient.

PMID- 9651595
TI  - Development of an example flow test object and comparison of five of these test
      objects, constructed in various laboratories.
AB  - Doppler test objects are used to characterise Doppler systems, both stand-alone
      systems and the Doppler part of so-called duplex scanners. The aim of the project
      partially presented here is the development and validation of an example of a
      Doppler test object fulfilling the requirements of the IEC 1685. The project has
      been carried out by nine partners of five European countries and has been funded
      by the European Commission. The flow Doppler test object is composed of: tissue
      mimicking material (TMM), blood mimicking fluid (BMF), tube (embedded in the TMM
      and carrying the BMF), tank flow system, including a pump and a flow meter. In
      the normative part of the IEC 1685, requirements are given for the values of
      acoustical parameters of TMM and BMF such as sound velocity, attenuation and
      backscattering. For BMF, requirements are given also for values of density and
      viscosity. In an informative (but not compulsory) annex, a description is given
      of a flow test object meeting these requirements as an example. 'example test
      object' developed during the project is composed of TMM based on agar and
      including SiC- and Al2O3-powders, BMF based on nylon particles suspended in water
      and glycerine, and a tube of c-flex, a silicon copolymer. Two tube sizes are
      used: 4.0 mm ID and 8.0 mm ID. During the project, very precise recipes have been
      developed for the composition and preparation of both TMM and BMF. Based on these
      recipes and a description of the construction in a design five flow test objects
      have been constructed in the laboratories of five participants. The test objects
      have been compared by measurements of the physical parameters and by Doppler
      measurements of the five test objects with the Doppler system. The measurements
      have been carried out by five observers. Inter-test object and inter-observer
      variabilities are determined, yielding information about usefulness of the
      parameters.

PMID- 9651597
TI  - Design and in vitro results of a high intensity ultrasound interstitial
      applicator.
AB  - Interstitial technologies were proposed for the treatment of deep-seated and
      unresectable tumours. This study was designed to demonstrate the possibility of
      producing coagulation necrosis for a short exposure duration (20s) and a large
      volume with an interstitial ultrasonic applicator equipped with a plane
      transducer. The applicator was evaluated in terms of electroacoustic efficiency
      (58% at 10.7 MHz), temperature pattern and in vitro pig liver tissues
      destruction. The temperature elevation reached 52, 39, 22 and 15 degrees C at,
      respectively, 2.5, 7.5 and 10 mm from the applicator surface along the
      propagation axis. The evident cigar-shaped lesions spread on a depth of (8 +/- 2)
      mm from the surface applicator, (10 +/- 1) mm high and (3 +/- 1) mm high and (3
      +/- 1) mm wide. The temperature measurements showed the limitations encountered
      with a 10 MHz transducer. The high increase in temperature of tissues close to
      the transducer can induce vaporisation and a gaseous barrier opaque to
      ultrasound. Owing to the shape and the operating frequency of the transducer, we
      hope to obtain the same satisfactory performances in vivo with weakly perfusion
      dependent lesions. Axial and longitudinal applicator motions will enable us to
      treat more important volumes.

PMID- 9651598
TI  - The generation of negative pressure waves for cavitation studies.
AB  - A technique for producing strong focused negative pressure waves in water is
      described. The method is based on the phase inversion of the planar shock wave
      from an electromagnetic transducer. This is achieved by reflection and focusing
      at a pressure release boundary. The acoustic concentrator has a phase inverting
      central element and a phase maintaining annular mirror. Focal pressures of
      approximately -16 MPa from an initial +5 MPa EMAT source have been measured and
      the focal volume was found to be approximately the same as that obtained with a
      conventional ultrasonic lens. The electromagnetic transducer and the parabolic
      concentrator is an excellent source of cavitation bubbles in water. The focused
      negative wave has been observed using high speed laser-lit Schlieren photography.

PMID- 9651600
TI  - On the effect of lung filtering and cardiac pressure on the standard properties
      of ultrasound contrast agent.
AB  - The goal standard of contrast echocardiography is the absolute measure of
      myocardial perfusion using a contrast agent. Actually, several contrast agents
      are developed. All these agents show left ventricular opacification after
      intravenous injection. However, none of these agents shows an acceptable
      enhancement of the myocardium yet using conventional imaging techniques. The
      explanation of this phenomenon should be easy by measuring the acoustic
      characteristics of the contrast agent and then making a comparison of these
      characteristics with those of the myocardium. In this study we present
      definitions of standard acoustic parameters of ultrasound contrast agent, the
      backscatter coefficient Bs and the scattering-to-attenuation ratio STAR.
      Afterwards, considering an intravenous injection of the contrast agent, and
      taking into account the effects of lung filtering and cardiac pressure, the
      standard properties of contrast agents are determined in different sites: right
      ventricle (before lung passage), left ventricle (after lung passage and taking
      into account the pressure effect) and in the coronary system. Calculations showed
      that the acoustic properties are considerably influenced by these two effects:
      lung filtering and cardiac pressure. Comparison of these properties with the
      tissue properties (myocardium) is then performed. This determines the
      contribution of the contrast agent to the enhancement of the tissue
      visualization. The simulations are performed on Albunex microspheres. The results
      reveal that the difference between scattering of the myocardium and scattering of
      intravenously injected Albunex is too slight to be visible on an echographic
      image.

PMID- 9651599
TI  - Clinical applications of ultrasound contrast agents.
AB  - Within the last decade safe and practical ultrasound contrast agents have been
      introduced. Most of these are based on gas-filled microbubbles, which markedly
      enhance Doppler signals and, in some cases, also gray-scale images. The clinical
      improvements expected from ultrasound contrast is reviewed. Tissue-specific
      contrast agents constitute another area of potential clinical significance. One
      particular agent is taken up by the reticulo-endothelial system and produces so
      called acoustic emission signals when imaged. An introduction to the unique
      clinical applications of acoustic emission is given. Harmonic imaging is a new
      contrast-specific imaging modality, which utilizes the nonlinear properties of
      some agents in an attempt to alleviate current limitations of ultrasound contrast
      studies. Examples of harmonic images are presented.

PMID- 9651601
TI  - Effect of ultrasound on the release of micro-encapsulated drugs.
AB  - Although ultrasound is used extensively in medical therapies and diagnostics, it
      has been recognized only recently as a method for external controlled diversity
      of drugs. In this paper, firstly, a literature review on drug delivery and the
      combination with ultrasound is given. Then an experiment is described on
      measuring the release of a model drug (hexabrix) under ultrasound irradiation,
      from a polymer carrier.

PMID- 9651603
TI  - [Predictive factors for development of hemolytic uremic syndrome (HUS) and early
      intensive treatments for prevention of HUS enterohemorrhagic Escherichia coli
      infection].
AB  - Predictive factors for the development of hemolytic uremic syndrome (HUS) were
      evaluated in 88 inpatients who suffered from enterohemorrhagic E. coli infections
      in the outbreak in Sakai, 1996. All in- and outpatients received oral or
      intravenous fosfomycin within acute phase of hemorrhagic colitis, and HUS
      complicated 1.4% of them. Persistence of bloody stools and diarrhea were longer
      in HUS patients than in non-HUS patients, but persistence of abdominal pain was
      not different in either group. Leukocytosis with leukocyte counts over
      15,000/microliters and/or elevated CRP level over 2.0 mg/dl at admission, and
      fever and/or vomiting in the course of hemorrhagic colitis were more frequent in
      HUS patients than in non-HUS patients. Early intensive treatments including
      gammaglobulin, urinastatin, aspirin, and dipyridamole were employed in 34 high
      risk patients for prevention of HUS. These patients were estimated to be at risk
      of developing HUS because of incomplete HUS, nephropathy, elevated LDH level,
      thrombocytopenia, or age younger than two years old. These treatments were
      clinically effective.

PMID- 9651602
TI  - Characterising ultrasonic physiotherapy systems by performance and safety now
      internationally agreed.
AB  - The IEC 1689 standard specifies: methods of measurement, characterisation of the
      output performance, requirements for safety due to the ultrasonic field
      generated, characteristics to be declared by manufacturers and acceptance
      criteria for aspects of performance. For the characterisation, reference as well
      as routine testing methods are described. Important parameters such as effective
      radiating area (AER), beam nonuniformity ratio (RBN) (characterising 'hot-spots':
      potentially harmful to patients) and beam type have been re-defined. The quality,
      reproducibility and accuracy of measurements of AER are significantly improved
      compared to those in IEC 150 (which is now replaced) and the FDA 1050.10 (USA)
      standards. As a result, values of effective intensity are shown to be
      significantly higher than those obtained using the FDA 1050.10 (USA) definitions.
      As it may be expected that the new standard will be implemented worldwide, this
      problem is just a matter of time. The standard discussed above specifies the need
      for acoustic power measurement with an accuracy of more than 15%. However,
      several investigations carried out over the last ten years show a lack of proper
      facilities to calibrate the acoustic output power at physiotherapy levels. A
      project to investigate the complications and to produce definitive guidance for
      therapy-level power measurements is funded by the EC and has been started
      recently. Future activities will be undertaken to estimate the expected
      temperature rise in tissue due to the ultrasonic field. Such a figure may result
      in an improved judgement of the ultrasonic safety aspects of physiotherapy
      systems.

PMID- 9651604
TI  - [Efficacy and safety of sulbactam/cefoperazone for hepato-biliary infections].
AB  - We studied efficacy and safety of sulbactam/cefoperazone (SBT/CPT) in the
      treatment of biliary tract infections in hospitalized patients at 26 hospitals
      from February 1993 to March 1995. Secondary to dropout, 273 out of 338 patients
      entered in the study were evaluated, 127 patients with cholecystitis, 132
      patients with cholangitis, and 14 patients with liver abscesses. Of these, 93
      patients (34.1% had malignancy as an underlying disease. SBT/CPZ had an efficacy
      of 79.9% (218 patients; excellent: 52, good: 166), with the efficacy in patients
      with cholecystitis, cholangitis and liver abscess at 89.0% (113 patients), 77.3%
      (102 patients and 21.4% (3 patients), respectively. A significant difference (p <
      0.05) was observed in the efficacy rates of patients with (59 patients [63.4%])
      and without malignancy (159 patients [88.3%]). A total of 84 strains were
      isolated from bile specimens of 53 patients, and the major isolates were
      Escherichia coli, Pseudomonas aeruginosa and Enterococcus spp. Two or more
      bacterial strains were isolated simultaneously in 20 patients. Mild or moderate
      side effect (allergic reaction including rash etc.) were noted in 4 patients
      (1.18%), and laboratory abnormalities (increased GOT, etc.) were in 16 patients
      (4.71%) out of the total 338 patients. This study clearly demonstrated that
      SBT/CPZ retains its excellent clinical efficacy and safety profile, throughout
      its use over the past decade.

PMID- 9651605
TI  - Concentration of levofloxacin in cervical mucus and its clinical effects on
      cervicitis.
AB  - An investigation was made on the concentration of levofloxacin (LVFX) in cervical
      mucus and its clinical effects on cervicitis. The results were as follows: 1) The
      concentrations of orally administered LVFX in the cervical mucus of 110 subjects
      were determined by HPLC. During 1-4 hour after the administration the mean
      concentration of LVFX in the cervical mucus reached a level of 2 micrograms/g,
      which was higher than the serum level. The transfer of LVFX to the cervical mucus
      was almost the same as that to other genital organs. 2) When LVFX was given to
      102 patients at a dose of 100-200 mg, t.i.d for 4-5 days and the efficacy was
      evaluated with clinical improvement, the clinical efficacy rate of LVFX was
      72/102 (70.6%). Significant bacteriological effects were observed in 70/73
      (95.9%), especially, the disappearance rate of C. trachomatis was 18/18 (100%).
      3) The administration LVFX did not cause any subjective or objective side effects
      and any abnormalities were not detected in the laboratory test done in this
      study. These results demonstrate that LVFX can be sufficiently transferred to the
      cervical mucus for the treatment of cervicitis due to the infection of C.
      trachomatis etc.

PMID- 9651606
TI  - [Antimicrobial activities of clindamycin against clinical isolated Streptococcus
      pneumoniae].
AB  - We investigated antimicrobial activity of clindamycin (CLDM) against clinically
      isolated Streptococcus pneumoniae in 1996. The results are summarized as follows;
      1. The detection frequencies of macrolides (MLs)-resistance against penicillin
      (PC)-susceptible S. pneumoniae (PSSP) was 48.0% and those against PC-intermediate
      S. pneumoniae (PISP)/ PC-resistant S. pneumoniae (PRSP) was 92.0%. 2. It was
      found that the ratio of MLs-inducible resistant strains of PSSP was 24.6% and
      that of PISP/PRSP was 66.0%. MLs-constitutive resistant strains of PSSP accounted
      for 24.0% and that of PISP/PRSP for 26.0%. MLs-constitutive resistant strains was
      relatively frequent in PSSP and MLs-inducible resistant strains was frequent in
      PISP/PRSP. 3. CLDM showed strong antimicrobial activity against MLs-inducible
      resistant strains. The MIC70 of CLDM against PSSP was < or = 0.025 microgram/ml
      and that against PISP/PRSP was 0.1 microgram/ml. From these results, it was
      suggested that CLDM is effective against the infection of PISP/PRSP where the
      detection frequency of MLs-inducible strains was high. 4. Antimicrobial activity
      of CLDM was found to be strong against MLs-inducible resistant strains, but to be
      weak against MLs-constitutive resistant strains. When S. pneumoniae is detected,
      susceptibility of the strain to CLDM should be examined.

PMID- 9651607
TI  - [Studies on penetration of cefepime into respiratory tract using broncho-alveolar
      lavage and sputum].
AB  - We investigated broncho-alveolar distribution of cefepime (CFPM), a fourth
      generation cephem, using 38 BALF specimens from 19 serious pneumonia patients who
      underwent artificial respiratory system control. The mean broncho-alveolar CFPM
      level was 3.44 microgram/ml (5.34% of the mean peak blood level). We thus
      observed that the BALF level after a single dose of 1 g of CFPM exceeds the MIC90
      of the drug against RTI causing bacteria such as Streptococcus pneumoniae,
      Klebsiella pneumoniae, Haemophillus influenzae, Branhamella catarrhalis,
      coagulase-negative Staphylococcus, Pseudomonas aeruginosa and Staphylococcus
      aureus.

PMID- 9651608
TI  - Cochlear implantation: past and present.
AB  - Experimental stimulation of the ear started at the end of the 18th century with
      Volta. The first electrode implantation was performed by Djouno and Eyries in
      1957. This was followed by intensive cochlear implant research at first in
      California, then all over the world. During the past 2 decades there has been an
      evolution from single to high performance multichannel implants with the
      development of more sophisticated speech coding strategies.

PMID- 9651609
TI  - Cochlear implantation: an overview of existing implants.
AB  - Cochlear implants (CI) bypass the external and middle ear and parts of the inner
      ear, by delivering electrical stimuli to the remaining neural fibres of the
      acoustic nerve in a meaningful way. Many features of current CI are similar. They
      are all multi-channel devices with intracochlear placement of the active
      electrodes and with transcutaneous information and energy transfer. Factors
      affecting the auditory performance of CI recipients are patient-linked factors
      and device factors. An overview is given of key design parameters, processing
      characteristics and specifications of following CI platforms: Clarion S-Series,
      Combi 40 and Combi 40+, Digisonic DX 10, Laura-Flex and nucleus CI22 and CI24M.
      These data, combined with outcome parameters can enhance the information of CI
      teams, patients or parents of children in their decision making process when
      faced with a hearing impairment to such an extent that hearing aids are of little
      or no benefit.

PMID- 9651610
TI  - The LAURA Pediatric Cochlear Implant Program in Antwerp: what have we learnt in 5
      years?
AB  - The LAURA Cochlear Implant Program at the University of Antwerp was initiated 5
      years ago. Up to now 50 children have received the LAURA cochlear implant
      (Philips Hearing Implants). Our accumulated experience in selecting the patients,
      counselling their parents, implanting and fitting the device allowed us to
      gradually modify the inclusion/exclusion criteria for cochlear implantation and
      achieve very rewarding results. The most important change was the gradual shift
      towards a younger age at implantation, our youngest implantee being 11 months
      old. In this paper we describe the rationale for this change, as well as the
      prerequisites for a successful pediatric cochlear implant program.

PMID- 9651611
TI  - Congenitally deaf children following cochlear implantation.
AB  - The aim of this study is to determine the auditory performance of congenitally
      deaf children following cochlear implantation. A prospective study is undertaken
      of 71 such children who have been implanted in a dedicated paediatric cochlear
      implant centre and who have been followed up to 3 years following implantation.
      All children are aged less than 8 years at the time of implantation and all
      receive a multichannel cochlear implant system. No child meeting these criteria
      has been excluded from the study. The average age at implantation is 56.5 months
      (range 27 to 93 months, standard deviation 15.9 months). Auditory performance is
      assessed by using the Categories of Auditory Perception (CAP) scale which is
      developed primarily as a clinical tool for evaluating profoundly deaf young
      children following cochlear implantation. The median score prior to implantation
      on this scale is Category 0 (no awareness of environmental sound), at the 1 year
      interval is Category 4 (discrimination some speech sounds without lip-reading),
      and at the 2 and 3 year interval, the median score on the CAP scale is Category 5
      (understanding of common phrases without lip-reading). These results indicate the
      ability of cochlear implants to provide significant auditory receptive skills to
      young congenitally deaf children.

PMID- 9651612
TI  - New developments in cochlear implants.
AB  - Essential to improve the performance with cochlear implants is a better control
      of the electrode-nerve interface. The long-term stability of the electrode
      characteristics has to be guaranteed. Most important herein is to have a low and
      stable electrical impedance and to prevent fibrosis. Results of electrode coating
      and fibrosis-inhibiting products are described. To assess the properties of the
      electrode-nerve interface such as stimulation threshold, spatial selectivity and
      channel interaction, the electrically evoked compound action potential is
      measured. The measurement paradigm and the first results are described. Models of
      auditory nerve response to electrical stimulation can be used as a tool for
      cochlear implant fitting. A simple model is proposed and its predictions are
      compared with measured responses.

PMID- 9651613
TI  - Developments in speech processing for cochlear implants.
AB  - The status of speech processing for cochlear implants is reviewed. Points of
      interest to enhance further speech intelligibility based on improved signal
      processing, are discussed.

PMID- 9651614
TI  - Imaging and cochlear implant.
AB  - The auditory pathway imaging may be morphologic and/or functional. The high
      resolution computed tomography and the magnetic resonance imaging (MRI) provide
      an evaluation of the anatomical and structural landmarks useful for a safe and
      successful cochlear implantation. The electrical stimulations supplied by the
      cochlear implant give rise to ascending electrochemical activities reaching the
      cortex. These activities can be recorded with scalp electrodes by Evoked
      Potentials (EP) or fields techniques and eventually translated in isochronic or
      isopotential brain mapping. These techniques provide a very sharp temporal
      resolution with an imprecise spatial resolution. The late auditory EP of
      implantees are closely comparable to the responses of normal hearing people. The
      neuronal metabolism's increase is associated with a cerebral blood flow increase.
      Comparing regional cerebral blood flow (rCBF) between two or more conditions
      allows the localisation of brain areas involved in a fixed task. Single photon or
      positron emission tomography and functional MRI (fMRI) demonstrate cBF changes
      associated with an auditory stimulation. (f)MRI is contraindicated in cochlear
      implantees.

PMID- 9651615
TI  - Some reflections on distribution of centres for cochlear implants.
AB  - Belgian has about 10 million inhabitants. Flanders has five and a half million
      inhabitants and five "CI-implant centre". As the ENT-community is not able to
      find sensible solutions to regulate this absurdity of one CI-centre per one
      million inhabitants (in Antwerp even one per 150,000 inhabitants) some legal
      activity should be provided by the government.

PMID- 9651616
TI  - The additional hospital costs and outcome of the LAURA Cochlear Implant in the
      Department of Otorhinolaryngology, Head and Neck Surgery of the University
      Hospitals, Leuven.
AB  - The additional hospital costs and the effects of cochlear implantation are
      described. From the start in 1994 until 1996 ten patients, 8 adults and 2
      children, received a cochlear implant after careful preoperative selection. Only
      the 8 deaf adults implanted with the LAURA cochlear implant in the department of
      Otorhinolaryngology, Head and Neck Surgery of the University Hospital Leuven will
      be included in this retrospective analysis. In this study, the additional
      hospital costs associated with cochlear implantations are estimated. In
      estimating the costs, a differentation is made between 'fixed' costs and
      'variable' costs. In general the costs of cochlear implantation is high: an
      average cost of 1,186,741, -Bef per implanted adult and a direct fixed cost of
      262,880, -Bef for the computer requisites. To evaluate the effect of cochlear
      implantation a standard test, the AN-test battery, is used. In general, the
      cochlear implant enhances the speech perception scores in the postlingually
      deafened as well as in the prelingually deafened adults. After intensive
      training, all implanted adults of the University hospital Leuven could recognize
      the segmental aspects of speech with scores above the level of significance. The
      cochlear implant has also a positive psychological and social impact.

PMID- 9651617
TI  - A tentative exploration of the character of pediatric cochlear implant critique.
AB  - Deaf communities have resisted pediatric cochlear implants in many western
      countries since the introduction of the technique in the late 1970's. In this
      struggle they have been supported by quite a few scientists from a diverse,
      albeit social scientific background. The arguments of the latter have been the
      source of much misapprehension. In this paper we will explore this
      misapprehension by structurally probing for implicit conceptualisations of
      benefit and legitimation procedures in the discourse of proponents and opponents
      alike.

PMID- 9651618
TI  - OSHA's renewed mandate for regulatory flexibility review: in support of the 1984
      ethylene oxide standard.
AB  - BACKGROUND: The Regulatory Flexibility Act of 1980 requires that all federal
      agencies consider the impact of regulations on small entities. One of the
      provisions of the Act requires review of regulations ever 10 years to determine
      whether such regulations should be continued without changes, rescinded, or
      amended to make them more effective or less burdensome on businesses. The Small
      Business Regulatory Enforcement Fairness Act (SBREFA) of 1996 amended and
      expanded the Regulatory Flexibility Act. Most significantly, SBREFA entitles
      aggrieved small entities or their representative (e.g., trade associations) to
      sue OSHA for failure to fulfill Regulatory Flexibility Act requirements. In
      response to this new political reality, OSHA held the first public meeting of
      their kind in June of 1997 to gather information on the ethylene oxide and lock
      out/tag-out standards for the purposes of Regulatory Flexibility review. METHOD:
      This paper presents the development of the Regulatory Flexibility review process
      and details our analysis of the ethylene oxide standard using OSHA's eight
      Regulatory Flexibility review criteria. RESULTS: Great progress in ethylene oxide
      health and safety has been made since the promulgation of the standard in 1984,
      including a considerable decrease in average workshift exposures. Yet, important
      concerns remain, such as the lack of safer substitutes for EtO's most common
      uses, the widespread occurrence of accidental exposures to EtO that are not
      captured by personal monitoring, and the recent increase in the occurrence of
      catastrophic EtO explosions. CONCLUSIONS: Because of the considerable study that
      has been devoted to EtO and to the EtO standard, there is a very strong cases for
      either making the EtO standard more worker protective, or continuing the standard
      without change while improving outreach and enforcement efforts to address
      shortcomings. Other valuable standards for which fewer data exist may be
      inappropriately threatened by the Regulatory Flexibility review process.
      Importantly, Regulatory Flexibility review could be constructive if accompanied
      by appropriations to fund sound evaluation studies. Instead, it will likely
      divert OSHA's limited resources from the numerous urgent health hazard that await
      initial rule-making. As signified by the designation of "intervention
      effectiveness research" as one of the 21 priorities on the National Occupational
      Research Agenda, evaluation studies of OSHA standards and other interventions are
      urgently needed. The occupational health community's response to this need will
      play a crucial role in preserving hard-won protections, as well as in developing
      other urgently needed protections in the future.

PMID- 9651619
TI  - Construction injury rates may exceed national estimates: evidence from the
      construction of Denver International Airport.
AB  - BACKGROUND: Construction of Denver International Airport (DIA) provided a unique
      opportunity to describe the magnitude of injury on a major construction project
      for which complete data on injury and hours at risk were available for over
      32,000 employees working 31 million hours. METHODS: Comprehensive payroll data
      for all workers, who were paid standard Davis-Bacon wages, allowed calculation of
      person-hours at risk by job classification. Complete reporting, facilitated by a
      single workers' compensation plan covering all contracts and by an on-site
      medical clinic and designated provider system, allowed us to determine both total
      and lost-work-time (LWT) injury rate per 200,000 hours at risk by industrial
      sector, company size, and year of construction. Workers' compensation payment
      rates were calculated and compared with expected loss rates, derived by the
      National Council on Compensation Insurance, by sector, company size, and year.
      RESULTS: DIA's overall total injury rates were over twice those published by the
      Bureau of Labor Statistics (BLS) for the construction industry for each year of
      DIA construction. Differences in LWT injury rates were more modest. Total injury
      rates were also at least twice BLS's rates for all contractor sizes. The injury
      rate pattern by company size at DIA differed from BLS's in that small firms had
      injury rates that were lower than or comparable to most other size categories;
      BLS's rates for small firms were lower than those for all but the very largest
      (250 or more employees) contractors. DIA's total workers' compensation (WC)
      payment rate of $7.06 per $100 payroll was only 11% higher than Colorado-specific
      expected loss rates reported by the National Council on Compensation Insurance.
      DISCUSSION: Complete reporting, facilitated by the existence of a single WC plan,
      an on-sites medical clinic, and designated medical providers, yielded injury
      rates significantly higher than previously reported. The relatively small
      difference between DIA payment rates significantly higher than previously that
      the discrepancy between DIA's injury rates and national estimates is due to
      underreporting of non-LWT injuries of the BLS. The burden of on-site work-related
      construction injury may be higher and more costly than has been evident from
      national data.

PMID- 9651620
TI  - Risk factors for injury among construction workers at Denver International
      Airport.
AB  - BACKGROUND: The Denver International Airport construction project provided a rare
      opportunity to identify risk factors for injury on a large construction project
      for which 769 contractors were hired to complete 2,843 construction contracts.
      Workers' compensation claims and payroll data for individual contracts were
      recorded in an administrative database developed by the project's Owner
      Controlled Insurance Program. METHODS: From claims andy payroll data linked with
      employee demographic information, we calculated injury rates per 200,000 person
      hours by contract and over contract characteristics of interest. We used Poisson
      regression models to examine contract-specific risk factors in relation to total
      injuries, lost-work-time (LWT), and non-LWT injuries. We included contract
      specific expected loss rates (ELRs) in the model to control for prevailing risk
      of work and used logistic regression methods to determine the association between
      LWT and non-LWT injuries on contracts. RESULTS: Injury rates were highest during
      the first year of construction, at the beginning of contracts, and among older
      workers. Risk for total and non-LWT injuries was elevated for building
      construction contracts, contract for special trades companies (SIC 17), contracts
      with payrolls over $1 million, and those with overtime payrolls greater than 20%.
      Risk for LWT injuries only was increased for site development contracts and
      contract starting in the first year of construction. Contracts experiencing one
      or more minor injuries were four times as likely to have at least one major
      injury (OR = 4.0, 95% CI (2.9, 5.5)). CONCLUSIONS: Enhancement of DIA's safety
      infrastructure during the second year of construction appears to have been
      effective in reducing serious (LWT) injures. The absence of correlation between
      injury rates among contracts belonging to the same company suggest that targeting
      of safety resources at the level of the contract may be an effective approach to
      injury prevention. Interventions focused on high-risk contracts, including those
      with considerable overtime work, contracts held by special trades contractors
      (SIC 17), and contracts belonging to small and mid-sized companies, and on high
      risk workers, such as those new to a construction site or new to a contract may
      reduce injury burden on large construction sites. The join occurrence of minor
      and major injuries on a contract level suggests that surveillance of minor
      injuries may be useful in identifying opportunities for prevention of major
      injures.

PMID- 9651621
TI  - Occupational injuries among adolescents in Washington State, 1988-1991.
AB  - BACKGROUND: To characterize work-related injuries and illnesses in minors.
      METHODS: We analyzed Washington State workers' compensation claims from 1988
      through 1991. RESULTS: There were 17,800 claims among adolescents from age 11
      through 17 years accepted in the 4-year period, including three occupational
      fatalities, 22 amputations, and 464 fractures; 89% of all injuries occurred among
      the 16- and 17-year-olds. Claims were most frequent in restaurants, food stores,
      service industry, other retail and wholesale trade, and agriculture. Washington
      State census data were used for denominator in calculating injury rates for
      adolescents and adults. The crude injury rate for 16- and 17-year-olds employed
      at the time of the census was similar to that seen among adults (9.0 vs 10.4 per
      100 workers), despite that minors work fewer hours per year. The rate among boys
      was almost twice that seen among girls (11.7 vs. 6.4 per 100 workers). Highest
      rates, per 100 workers, were in public administration (27.0), construction
      (21.1), agriculture (11.4), and restaurants (11.0). Using census data for those
      working anytime over the course of the year and adjusted for the number of hours
      worked, the injury rate for 16- and 17-year-olds was 19.4/100 full time
      equivalents compared with 10.6 of 100 full-time equivalents for adults. Most
      injuries were lacerations, sprains and strains, contusions, and burns.
      CONCLUSIONS: Public health policy and injury prevention strategies for working
      adolescents should be developed and implemented.

PMID- 9651622
TI  - Evaluation of narrative text for case finding: the need for accuracy measurement.
AB  - This article reviews the analysis of a narrative text electronic search technique
      being used in the insurance industry. We reviewed a previously published study of
      motor vehicle crashes in roadway construction workzones as well as additional
      data supplied by the authors with respect to the methods of keyword selection.
      The narrative text search technique was evaluated with decision statistics and
      was found to have a sensitivity of 92.3%, 95% confidence interval 67.5%-99.6%.
      This range of sensitivity, at its most extreme value, led to a 32.5%
      underestimation of claims prevalence. Furthermore, because the electronic search
      developed two classification categories from a limited text field (approximately
      20 words), only half of the cases had at least one classification. Systematic
      error estimates were used to obtain true population proportions for crash
      characteristics, revealing significant underestimations in costs. This analysis
      highlights the need for investigators to apply decision statistics to narrative
      text searching techniques when they are used essentially as diagnostic test
      procedures on insurance claims datasets.

PMID- 9651623
TI  - Pathomechanisms and pathophysiology of isocyanate-induced diseases--summary of
      present knowledge.
AB  - During recent years in Western countries, diisocyanates are one of the main
      causes of occupational asthma. The mechanism of diisocyanate-induced asthma is
      still unknown but recent evidence suggests immunological mechanisms, including
      cell-mediated immune responses. Immune responses to isocyanates may result in
      different illnesses, cell- and/or antibody-mediated entities. In addition,
      irritative, toxic, and mutagenic effects may occur. This review summarizes
      current knowledge of the pathomechanisms, including immunological and
      nonimmunological (mutagenic and genotoxic) aspects of isocyanate disorders.

PMID- 9651624
TI  - Associations between several sites of cancer and occupational exposure to
      benzene, toluene, xylene, and styrene: results of a case-control study in
      Montreal.
AB  - BACKGROUND: Except for the leukemogenic effects of benzene, there is inadequate
      or sparse evidence on the carcinogenicity of the most common monocyclic aromatic
      hydrocarbons. The purpose of this study was to generate hypotheses on
      associations between exposure to benzene, toluene, xylene, and styrene and
      various common types of cancer. METHODS: In the context of a population-based
      case-control study carried out in Montreal, 3,730 cancer patients (15 types of
      cancers, not including leukemia) and 533 population controls were interviewed,
      and their job histories were translated by a team of experts into occupational
      exposures, including benzene, toluene, xylene, and styrene. In the present
      analysis, exposure to these substances was compared between each case series and
      a control group pooling selected cancer patients and population controls, using
      logistic regression analysis. RESULTS: Exposure levels were low for most exposed
      subjects, and there was a high correlation between exposure to benzene, toluene
      and xylene. For most sites of cancer there was no evidence of excess risk due to
      these substances. However, limited evidence of increased risk was found for the
      following associations: esophagus-toluene, colon-xylene, rectum-toluene, rectum
      xylene and rectum-styrene. CONCLUSIONS: These latter observations warrant further
      investigation.

PMID- 9651625
TI  - Cancer incidence among Ontario police officers.
AB  - The National Institute for Occupational Safety and Health (NIOSH) published a
      report in 1995 suggesting the possibility of increased incidence of testicular
      cancer, leukemia, and cancers of the brain, eye, and skin among police officers
      working with traffic radar. NIOSH recommended epidemiologic study of the issue.
      This report presents the results of a retrospective cohort cancer incidence study
      among 22,197 officers employed by 83 Ontario police departments. The standardized
      incidence ration (SIR) for all tumors sites was 0.9% (95% confidence interval
      [CI] = 0.83-0.98). There was an increased incidence of testicular cancer (SIR =
      1.3, 90% CI = 0.9-1.8) and melanoma skin cancer (SIR = 1.45, 90% CI = 1.1-1.9).
      These anatomical sites might absorb energy from radar units, but at this time the
      author has no information about individual exposures to radar emissions, and it
      is not possible to draw etiologic conclusions. Nested case-control studies are
      planned to assess individual radar exposures.

PMID- 9651626
TI  - Work-related respiratory symptoms and lung function in New Zealand mussel
      openers.
AB  - Our objectives were to measure the prevalence of work-related and nonwork-related
      respiratory symptoms in a group of New Zealand mussel openers who open green
      lipped mussels, and to relate these to demographic factors, work history, smoking
      history, and pulmonary function measurements. A cross-section study of
      respiratory symptoms and lung function was performed on 224 New Zealand mussel
      openers (99.6% of the study population) at nine work sites. In addition, peak
      expiratory flow (PEF) change across-shift was measured at one work site in 19
      workers. The mean age of all mussel openers was 33.4 years and the mean duration
      of mussel opening was 5.0 years; 25% were male, 54.7% were current smokers, and
      13.9% were ex-smokers. The reported symptom prevalences were: any wheeze, 35%;
      work-related wheeze, 23%; any chest tightness, 30.5%; work-related chest
      tightness, 20.2% (work-related symptoms were defined as symptoms improving on
      rest days or worse at work). Seventy-two mussel openers (32.3%) answered
      positively to at least 1 of 4 questions concerning work-related symptoms. The
      mean predicted FEV1 (SD) for this group was 74.3% (14.5), and the mean predicted
      FVC (SD) was 79.2 (16.0). Nineteen workers completed serial PEF, and the mean
      percentage change was +1.5% at 7 hr, but 8 workers had falls ranging between 1.1
      14% after either 1 or 7 hr of work. Duration of mussel opening of greater than 2
      years, but less than 7 years (OR = 2.29; 95% CI, 1.07-4.91), and duration of
      mussel opening greater than 7 years (OR = 3.72; 95% CI, 1.52-9.11), were
      significant predictors of work-related respiratory symptoms. Female sex (OR =
      1.73; 95% CI, 0.83-3.60) was also associated with the presence of work-related
      symptoms. No relationship was found with measured hygiene parameters of cleaning
      agents used. In conclusions, duration of work as a mussel opener was associated
      with the present of work-related respiratory symptoms, after adjustment of age,
      sex, and smoking habit. There were marked abnormalities in mean FEV1 and FVC,
      although no consistent changes across working shift were noted.

PMID- 9651627
TI  - Dermal and respiratory sensitization to chromate in a cement floorer.
AB  - BACKGROUND: To report a well-documented case of both allergic contact dermatitis
      and occupational asthma due to chromate exposure in a 48-year-old floorer.
      METHODS AND RESULTS: A 48-year-old floorer, occupationally exposed to cement and
      with a documented chromate contact dermatitis, reported dyspnea and wheezing
      after work. These conditions were demonstrated by self-measured sequential peak
      expiratory flows. A first bronchial provocation (BPT) with potassium dichromate
      (K2Cr2O7) (0.3% nebulized for a total of 60 minutes) led to pronounced and
      sustained decreases in forced expiratory volume in 1 second (FEV1) and forced
      vital capacity, accompanied by pruritus, a decrease in arterial PO2, a slight
      rise in temperature, and peripheral blood leukocytosis. (This concentration of
      K2Cr2O7 is not recommended for BPT). Bronchoalveolar lavage performed 2 days
      later showed 18% eosinophils. Tow years later, a BPT with a lower dose of K2Cr2O7
      (0.01% for the total of 31 min) led to an "earl late" reaction (FEV1 dropped by
      195 compared with the initial FEV1 value), accompanied by pruritus. A BPT with
      dry cement, containing 12 ppm hexavalent chromium, was borderline (FEV1 dropped
      by 13%), and a similar result (FEV1 dropped by 14%) was obtained after smoking
      five cigarettes, laced with 10 mg of cement per cigarette. CONCLUSIONS: This
      report illustrates that a subject, with allergic contact dermatitis to chromates,
      may develop a respiratory allergic reaction to an airborne source of this metal.
      The main novelty of our report is that the smoking of cigarettes contaminated
      with cement may have been significant factor in the causation or elicitation of
      these reactions.

PMID- 9651628
TI  - Evaluation of workers exposed to dust containing hard metals and aluminum oxide.
AB  - BACKGROUND: Fourteen worker exposed to hard metals and aluminum oxide were
      evaluated. METHODS: Six heavily exposed workers underwent bronchoscopy and
      bronchoalveolar lavage, and five workers underwent transbronchial biopsy.
      RESULTS: Microchemical analysis of transbronchial biopsies showed a high lung
      burden of exogenous particles, especially metal related to their hard metals
      exposure. Lung tissue and cellular changes, which were associated with exposure
      to hard metal and aluminum oxide, corresponded well with the microanalytic test
      results. CONCLUSIONS: Three workers had at biopsy diffuse interstitial
      inflammatory changes: two of them were asymptomatic with normal chest X-ray
      films, and one had clinically evident disease with severe giant cell
      inflammation. Two other workers showed focal inflammation. The worker showing
      clinical disease and one asymptomatic worker with interstitial inflammatory
      changes had evaluated bronchoalveolar lavage fluid-eosinophilia counts. These two
      were father (with clinical disease) and son (asymptomatic).

PMID- 9651629
TI  - Toxigenic fungi in a water-damaged building: an intervention study.
AB  - In an investigation of health complaints among employees of a water-damaged
      office building, the environment showed evidence of fungal contamination with the
      isolation of Stachybotrys chartarum in one of five bulk samples tested for fungal
      growth. In response, a public health official recommended that employees be
      relocated from the building. Employees were subsequently moved to a different
      environment. A focused environmental investigation of microbial growth within the
      building followed, revealing moderate to high levels of fungi (Penicillium,
      Aspergillus versicolor) and bacteria in bulk and surface samples. S. Chartarum
      was identified in one of 19 (5%) environmental samples using Czapek agar. A
      health survey of building occupants revealed a high prevalence of multiple
      symptoms, with the predominance of neurobehavioral and upper respiratory tract
      complaints. The majority of symptoms were significantly less prevalent after
      relocation from the water-damaged environment. The initial hypothesis that
      exposure to toxigenic fungi was responsible for the high prevalence of reported
      symptoms is difficult to investigate and confirm given the current limits of
      epidemiological knowledge regarding exposure to these organisms and building
      related illness. Future interventions where mycotoxin exposure is suspected
      should emphasize the importance of risk assessment and risk communication.

PMID- 9651630
TI  - Lead exposure in a developmentally disabled workforce.
AB  - Over-exposure to lead was identified among developmentally disabled workers
      engage in furniture refinishing at two separate sites. The index case was
      identified at the first site by a public health nurse assigned to provide care to
      some of the workers. Referral to a regional occupational health clinic initiated
      an exposure assessment and medical consultation at both work sites. Blood lead
      levels (BLLs) among sanders and helpers at site A averaged 60 micrograms per
      deciliter of blood (mcg/dl). At site B, BLLs were lower, but 6 individuals had
      BLLs greater than mcg/dl. Hand sanding of chemically stripped wood previously
      coated with lead-based paint was determined to be the exposure source. These
      incidents document potential lead overexposure in an underecognized setting. They
      also emphasize the importance of incorporating a workplace health risk assessment
      in the process of placing and protecting the developmentally disabled on the job.

PMID- 9651631
TI  - Asbestos-related x-ray changes in foundry workers.
AB  - Michigan has a statewide mandatory occupational disease reporting system. As part
      of that system, reports are received from hospital, physicians, death
      certificates, the worker's compensation bureau, and company medical departments.
      Based on this reporting, the State of Michigan has a special emphasis program for
      the surveillance of silicosis, a known disease outcome among foundry workers.
      From 1985-1996, 115 cases reported to the State Surveillance System as silicosis,
      pneumoconiosis not specified, or pulmonary fibrosis were reclassified as having
      asbestos related x-ray changes after a B-reader interpretation of each case's
      chest x-ray. During this same period there were an additional 697 reports
      confirmed as silicosis and 6,724 cases reported to the surveillance system as
      asbestosis. Among the 115 reports reclassified as having asbestos-related x-ray
      changes without evidence of silicosis-related x-ray changes, 54 had worked in
      foundries. Only 7 (14.8%) of these individuals had their primary work in
      maintenance in the foundry; 40 (85.1%) had their primary foundry work in a
      production job; and for 10 individuals the occupation was not known. Asbestos has
      been used in foundries on pipe laggings, boiler coverings, as insulation in fan
      housings, in gloves, aprons and curtains, as insulation in cupolas, and in ladles
      and insulation in sand molds. Clinicians caring for foundry workers need to be
      aware that asbestos-related x-ray changes are not uncommon in this population and
      asbestos exposure should be considered as one of the carcinogens contributing to
      the known increased risk of lung cancer among foundry workers.

PMID- 9651633
TI  - Smokers' misperceptions of light and ultra-light cigarettes may keep them
      smoking.
AB  - INTRODUCTION: This study examined smokers' understanding of the relative tar
      deliveries of Ultra-light, Light, and Regular cigarettes, reasons for smoking
      Ultra-light/Light cigarettes, and the likelihood of both quitting smoking and
      switching to Regular cigarettes if they came to learn that one Ultra-light/Light
      cigarette gave the same amount of tar as one Regular cigarette. DESIGN: Ten- to
      fifteen-minute random-digit-dialed, computer-assisted telephone interviews (CATI)
      were conducted with both a national probability sample (n = 788) and a state
      random sample (n = 266) of daily smokers over the age of 18. RESULTS: Less than
      10% of smokers in the national sample and only 14% of smokers in the state sample
      knew that one Light cigarette could give the same amount of tar as one Regular
      cigarette. Less than 10% of smokers in the state sample knew that one Ultra-light
      cigarette could give the same amount of tar as one Regular cigarette. Thirty-two
      percent of the Light and 26% of the Ultra-light smokers in the national sample,
      and 27% of Light and 25% of Ultra-light smokers in the state sample, said they
      would be likely to quit smoking if they learned one Light/Ultra-light equaled one
      Regular. CONCLUSION: Many Light and Ultra-light smokers are smoking these
      cigarettes to reduce the risks of smoking and/or as a step toward quitting.
      However, these smokers are unaware that one Ultra-light/Light cigarette can give
      them the same amount of tar and nicotine as one Regular cigarette. Many of the
      Ultra-light/Light smokers sampled in this study stated that they would be likely
      to quit if they knew this information. Mistaken beliefs about low-yield brands
      are reducing intentions to quit smoking.

PMID- 9651632
TI  - Immunogenicity of hepatitis B Vaccines. Implications for persons at occupational
      risk of hepatitis B virus infection.
AB  - OBJECTIVE: To assess risk factors for decreased immunogenicity among adults
      vaccinated with hepatitis B vaccine and to determine the importance of
      differences in immunogenicity between vaccines among health care workers (HCWs).
      DESIGN: Randomized clinical trial and decision analysis. PARTICIPANTS: HCSw. MAIN
      OUTCOME MEASURES: Development of seroprotective levels of antibody to hepatitis B
      surface antigen (anti-HBs) and the number of expected chronic hepatitis B virus
      (HBV) infections associated with lack of protection. RESULTS: Overall, 88% of
      HCWs developed seroprotection. Risk factors associated with failure to develop
      seroprotection included increasing age, obesity, smoking and male gender (P <
      .05). Presence of a chronic disease was associated with lack of seroprotection
      only among persons > or = 40 years of age (P < .05). The two vaccines studied
      differed in their overall seroprotection rates (90% vs. 86%; P < .05), however,
      this difference was restricted to persons > or = 40 years of age (87% vs. 81%; P
      < .01). Among HCWs > or = 40 years of age, the decision analysis found 44
      (0.34/100,000 person-years) excess chronic HBV infections over the working life
      of the cohort associated with use of the less immunogenic vaccine compared to the
      other. CONCLUSIONS: He patitis B vaccines are highly immunogenic, but have
      decreased immunogenicity associated with increasing age, obesity, smoking, and
      male gender; and among older adults, the presence of a chronic disease. One of
      the two available vaccines is more immunogenic among older adults; however, this
      finding has little clinical or public health importance. Hepatitis B vaccines
      should be administered to persons at occupational risk for HBV infection early in
      their career, preferably while they are still in their training.

PMID- 9651634
TI  - Factors associated with smoking among children and adolescents in Connecticut.
AB  - INTRODUCTION: The age of smoking initiation has dropped over the past four
      decades. Since behaviors and attitudes adopted in late childhood or early
      adolescence predict future smoking, it is important to understand the smoking and
      other risk-taking behaviors and attitudes of children aged 12 and younger. The
      goal of the analyses presented here was to describe behavioral and attitudinal
      factors associated with smoking among elementary school (grades 4-6), middle
      school (grade 7-8), and high school (grades 9-12) students in Connecticut.
      METHODS: We have used data from 8 years (1988-1996) of an anonymous, self
      administered health risk appraisal survey given to children and adolescents in
      self-selected public and private schools. We compared the proportion of smokers
      and nonsmokers who reported various behaviors and attitudes and compared them
      with the chi-square test. RESULTS: Fifteen percent (n = 4,884) of the total
      population (n = 31, 861) were current smokers. At all grade levels, current
      smokers were more likely than nonsmokers to engage in risk-taking behaviors, and
      to report more stress and depression. Indicators of risk-taking and stress were
      also associated with the intent to smoke among children in grades 4-6.
      CONCLUSIONS: Smoking occurs within the context of other risk-taking behavior and
      psychological distress, among both children and older adolescents. Our data
      provide support for the idea of early identification and targeting of children at
      high risk of smoking in elementary school, possibly as early as grade four.

PMID- 9651635
TI  - Smoking relapse prevention during pregnancy. A trial of coordinated advice from
      physicians and individual counseling.
AB  - INTRODUCTION: Our objective was to examine the efficacy of physicians' advice and
      referral to individual counseling in preventing relapse to smoking among women
      who were smokers early in pregnancy, but quit prior to their first prenatal
      visit. DESIGN: A randomized controlled trial of prompted physician's advice and
      individual relapse prevention counseling during pregnancy compared to usual
      physician advice. Smoking status was assessed by self-report, exhaled carbon
      monoxide, and urinary cotinine during pregnancy and by self-report 1 year
      postpartum. RESULTS: There were no significant differences in relapse rates
      between the intervention and usual-care groups during pregnancy, nor at 1 year
      postpartum. Relapse rates were 23% in both groups at the 36-week visit, and 32%
      and 22%, respectively, 1 year postpartum. Younger age, higher motivation to
      resume smoking, and higher levels of exhaled carbon monoxide at the first
      prenatal visit were predictive of relapse to smoking during pregnancy. With the
      conservative assumption that all those lost to follow-up relapsed, the combined 1
      year postpartum relapse rate, 51%, was 17 percentage points lower than we
      observed in an earlier relapse prevention trial, and 15 percentage points lower
      than that observed nationally a decade earlier. CONCLUSION: Prompting physicians
      to provide supportive advice combined with referral to individual relapse
      prevention counseling did not reduce smoking relapse rates during pregnancy, or
      postpartum. However, the level of attention paid to smoking by physicians in both
      intervention and usual-care groups during pregnancy may have contributed to the
      relatively low relapse rates seen 1-year postpartum.

PMID- 9651636
TI  - Por La Vida model intervention enhances use of cancer screening tests among
      Latinas.
AB  - OBJECTIVE: To describe the short-term impact of the intervention known as Por La
      Vida (PLV) on cancer screening for Latinas in San Diego, California. METHODS:
      Thirty-six lay community workers (consejeras) were recruited and trained to
      conduct educational group sessions. Each consejera recruited approximately 14
      peers from the community to participate in the program. The consejeras were
      randomly assigned to either a twelve-week cancer screening intervention group or
      a control group in which they participated in an equally engaging program
      entitled "Community Living Skills." Pre- and post-intervention self-report
      information was obtained from project participants on the use of cancer screening
      examinations. Outcome measures were changes in the percentages of women who had
      breast and cervical cancer screening test within the past year before and after
      the intervention occurred. Experimental and control groups were compared using t
      tests. Analyses were conducted using both consejeras and participants as the unit
      of analysis. RESULTS: The increase in the use of the cancer screening test was
      higher in the PLV cancer intervention group in comparison to women in the
      community living skills control group. CONCLUSIONS: Key to the PLV intervention
      model is the identification of natural helpers in the Latino community and their
      subsequent training in intervention based on social learning theory using
      culturally appropriate educational materials. The model is an effective and
      viable approach for increasing the use of cancer screening tests in Latinas of
      low socioeconomic level and low level of acculturation.

PMID- 9651637
TI  - Increased drug use among old-for-grade and dropout urban adolescents.
AB  - INTRODUCTION: In tracking the epidemic of drug use in our communities, much
      emphasis has been placed on identifying predictive variables. In this study, we
      examine the relationship between drug use and school progress among a sample of
      inner-city adolescents. METHODS: A blinded, anonymous questionnaire covering a
      variety of health risk behaviors was administered to 1,720 adolescent patients
      who visited our outpatient clinic. Participants were classified as age
      appropriate for last school grade completed, older than normal for grade, or as a
      dropout. A urine specimen was also collected in a blinded, anonymous fashion from
      each participant, and tested for five common substances of abuse. RESULTS: Nearly
      12% of participants tested positive for drugs. Participants who were old for
      grade were over 40% more likely to be positive for drugs than grade-appropriate
      respondents, while school dropouts were more than twice as likely to test
      positive. CONCLUSIONS: These results demonstrate that being old-for-grade (OFG)
      and being a dropout in our population are markers for being at higher risk of
      substance abuse.

PMID- 9651638
TI  - U.S. women physicians' residential radon testing practices.
AB  - INTRODUCTION: These analyses were designed to elucidate U.S. physicians'
      perception of residential radon risk, as measured by the prevalence of
      residential radon testing using a representative sample of U.S. women physicians
      from the Women Physicians' Health Study database. In addition, characteristics of
      women physicians who were more likely to have conducted a residential radon test
      were identified. METHODS: A random sample (n = 4,501 respondents) of U.S. women
      physicians aged 30 to 70 was obtained in the Women Physicians' Health Study.
      Analyses were conducted using SUDAAN. RESULTS: The overall prevalence of
      residential radon testing among respondents was 18%, 2- to 6-fold higher than any
      estimate of residential radon testing in the general population. The strongest
      relationship with radon testing observed through logistic regression was with
      marital status; age, ethnicity, and region of residence were also related.
      CONCLUSION: The study demonstrates that although U.S. women physicians are more
      likely to have conducted a personal residential radon test than the general
      population, 82% report not having done so. Increasing the awareness of physicians
      about the health risks associated with prolonged radon exposure will be essential
      if they are to play a role in addressing this important public health problem.

PMID- 9651639
TI  - The influence of psychosocial factors, alcohol, drug use on African-American
      women's high-risk sexual behavior.
AB  - OBJECTIVE: The present study examines psychosocial and behavioral influences,
      particularly drug and alcohol use, as correlates of inconsistent condom use and
      having multiple sexual partners during the past months among African-American
      women. METHODS: The cross-sectional study, conducted between May and June 1996,
      recruited a convenience sample of 180 African-American women in Birmingham,
      Alabama. Women completed a face-to-face interview that assessed alcohol and drug
      use, sexual behaviors, depression, condom use, and negotiation skills. RESULTS:
      The majority of women, 51.6% (n = 93), had used either alcohol or drugs during
      the previous month. Many women, 31.1%, consumed alcohol, 18.3% used marijuana,
      and 8.3% had smoked crack within the past month. Nearly 42.7% of women used
      condoms inconsistently in the past month and 13.3% of women had multiple sexual
      partners within the past month. A logistic regression model predicting
      inconsistent condom use indicated that women were less likely to use condoms if
      they consumed alcohol between 20 and 30 days of the month (OR = 2.8, 90% CI = 1.3
      5.9) and if they had not negotiated condom use (OR = 32.4, 90% CI = 7.9-131.6).
      The logistic regression model predicting multiple sexual partners indicated that
      women were more likely to have multiple sexual partners if they had smoked crack
      in the past month (OR = 5.3, 90% CI = 1.6-18.2). CONCLUSION: HIV sexual risk
      reduction interventions for African-American women need to address the
      overlapping epidemics of drugs, alcohol, and STDs. Additionally, HIV sexual risk
      reduction efforts should be incorporated into existing drug and alcohol treatment
      programs and STD clinics.

PMID- 9651640
TI  - Prevention of elderly suicide. Physicians' assessment of firearm availability.
AB  - INTRODUCTION: Physicians have a unique role to play in the prevention of elder
      suicide, yet they may not be sufficiently attentive to the prominence of firearms
      in the rising trend in suicide by elder persons. This study sought to examine the
      extent to which physicians inquired about firearms with their depressed and
      suicidal elderly patients and further identified factors associated with
      physicians' likelihood of asking about firearms. METHODS: A probability sample of
      300 primary care physicians in Illinois was drawn from the American Medical
      Association Physician Masterfile. Physicians were chosen from the specialties
      most likely to be involved with elderly persons: internal medicine and family
      practice. A mailed questionnaire yielded a 63% response rate. RESULTS: Although
      they were treating depressed and suicidal older patients, a sizable proportion of
      the respondents (42%) reported that they did not ask such patients or their
      family members whether they had access to a firearm. Several factors
      distinguished physicians who assessed for firearms from those who did not. The
      most salient predictors were: continuing medical education training in suicide
      risk assessment, expertise in geriatric mental health, confidence in diagnosing
      depression, having a patient mention suicide in the past year, and indicating
      patient reluctance as a barrier to mental health treatment. DISCUSSION:
      Physicians working with depressed and suicidal elderly persons need to be
      informed about the prevalence of elder suicide and about the likelihood of
      elderly persons using firearms as a method of suicide. Effective suicide
      prevention will require physician training that directly addresses geriatric
      mental health and firearm suicide, in particular, at the student, residency, and
      continuing education levels.

PMID- 9651641
TI  - Competencies for population-based clinical managers. A survey of managed care
      medical directors.
AB  - BACKGROUND: The evolution of American health care into integrated systems of
      delivery and finance requires a specialized set of population-based skills for
      physicians. The field of preventive medicine represents one source of this
      expertise. Specific competencies for the emerging area of managerial medicine
      have not been well delineated. METHODS: Using concept documents from the
      Residency Review Committee for Preventive Medicine and the American Board of
      Preventive Medicine, a list of proposed competencies for managerial medicine was
      identified. Surveys were mailed to medical directors of all members of the
      American Association of Health Plans and to a random sample of diplomates of the
      American Board of Preventive Medicine. Respondents were asked to rate the
      importance of these competencies for a population-oriented clinician manager.
      RESULTS: Areas rated highly by medical directors included health services
      research (including outcome research), quality assurance and improvement, health
      risk assessment and reduction, programmatic skills, and clinical preventive
      skills. Responses from preventive medicine specialists were similar, but placed
      lower emphasis on these skills. CONCLUSION: Despite its limited response rate,
      this survey may be useful in the implementation of specialty training in
      managerial medicine. Residency training programs may choose to emphasize specific
      content area that reflect the priorities expressed by physicians actively
      involved in management.

PMID- 9651642
TI  - Medical directors, managed care, and population medicine competencies. Old wine
      in new bottles.

PMID- 9651643
TI  - Hepatitis B immunization in health care workers. Dealing with vaccine
      nonresponse.

PMID- 9651644
TI  - Harm-reduction approaches to smoking. The need for data.

PMID- 9651645
TI  - The strength of the relation between prenatal care and low birthweight.

PMID- 9651646
TI  - American College of Preventive Medicine practice policy. Screening for prostate
      cancer in American men.

PMID- 9651647
TI  - Cranial allometry and geographic variation in slow lorises (Nycticebus)
AB  - A series of 20 craniodental measurements was obtained for two sister taxa:
      Nycticebus coucang (common slow loris) and N. pygmaeus (pygmy slow loris).
      Multivariate analysis of variance was performed with adult data to describe
      patterns of subspecific and specific variation in this genus. The geometric mean
      of adult cranial dimensions was compared to field data on latitudinal coordinates
      for available specimens to investigate if size variation in Nycticebus is clinal
      in nature. Ontogenetic series for larger-bodied N. coucang and smaller-bodied N.
      pygmaeus were compared to test the hypothesis that species and subspecific
      variation in skull form results from the differential extension of common
      patterns of relative growth. A MANOVA provides independent support of Groves's
      [pp. 44-53 in Proceedings of the Third International Congress on Primatology,
      Vol. 1 (Basel: S. Karger), in 1971)] classification of Nycticebus into two
      species, with four subspecies in the common slow loris and one form of the pygmy
      slow loris. Within N. coucang, cranial proportions for all four subspecies are
      ontogenetically scaled, and size differentiation is mainly clinal (Bergmann's
      Rule). N. c. bengalensis represents the most northerly disposed and the largest
      form. N. c. javanicus represents the next-largest form and is located in a
      southerly direction the next-farthest away from the equator. N. c. coucang and N.
      c. menagensis are both equatorial; however, the latter subspecies is the
      smallest. A genetic basis for some of the taxonomic variation between N. c.
      coucang and N. c. menagensis is supported by such nonclinal variation in body
      size. Variation in the presence/absence of I2 is not size-related but rather
      tracks geographic proximity and isolating factors which predate the most recent
      inundation of the Sunda Shelf. Although they inhabit a nonequatorial environment,
      pygmy slow lorises are the smallest of all Nycticebus. As N. pygmaeus is
      sympatric with N. c. bengalensis, the largest slow loris, it appears that the
      evolution of its smaller body size represents a case of character displacement.
      Unlike N. coucang, skull size becomes significantly smaller in more northern N.
      pygmaeus. This may also reflect character displacement between sympatric sister
      taxa underlain by a cline-dependent ecological factor which is marked in more
      northerly latitudes. On the other hand, the negative correlation between body
      size and latitude in N. pygmaeus could be due to the influence of nonprimate
      fauna, such as predators, which themselves evince a similar clinal pattern.
      Analyses of relative growth indicate that skull proportions in the two species of
      Nycticebus are ontogenetically scaled in two-thirds of the cases. All but one of
      the seven comparisons (interorbital breadth) which do not indicate ontogenetic
      scaling represent part of the masticatory complex. This likely reflects a
      reorganization of N. pygmaeus maxillomandibular proportions linked to smaller
      size and changes in diet.

PMID- 9651648
TI  - Differences in stress reactivity of laboratory macaques measured by heart period
      and respiratory sinus arrhythmia.
AB  - Some laboratory primates are more likely than others to react to anxiety
      provoking stressors. Individuals that overreact to stressors may experience
      diminished psychological well-being and would be inappropriate for some
      experiments. The differences between reactive and nonreactive individuals may be
      reflected in heart period and respiratory sinus arrhythmia (RSA). Using surface
      electrodes and radio telemetry, we measured these two cardiac variables in seven
      male and ten female singly caged longtailed macaques (Macaca fascicularis) when
      they were exposed to two stressors, a sudden noise (whistle test) and an
      unfamiliar technician wearing capture gloves (glove test). Behavior was
      videotaped during both tests. For the whistle test, cardiac data were recorded
      before, during, and after two 1 minute whistle blasts separated by 90 min. For
      the glove test, data were recorded in 1 minute blocks every 8 minutes over 96
      minutes before, during, and after 1 minute exposure to the gloved technician.
      Heart period was decreased and RSA was suppressed during both the whistle and
      glove exposures. After the whistle test, the cardiac activity of most subjects
      returned to baseline levels within 10 minutes. The glove test produced more
      extended suppression, with greater individual differences, than the whistle test.
      There were greater individual differences in RSA than in heart period. These
      enhanced individual differences were used to define stress reactors that differed
      from nonreactors in their cardiac data profiles. Of 16 subjects that completed
      the glove test, five were identified as reactors.

PMID- 9651649
TI  - Feeding ecology of the black howler monkey (Alouatta pigra) in northern Belize.
AB  - We studied the feeding ecology of the black howler monkey (Alouatta pigra) from
      March 1994 to April 1995 in the Community Baboon Sanctuary in northern Belize,
      Central America. Activity and diet composition were recorded using continuous
      focal animal sampling. Diet composition was compared with the relative abundance
      of plant parts eaten by the howlers within the study site. The study animals
      spent an average of 24.4% of their time feeding, 61.9% resting, and approximately
      9.8% traveling. In contrast to previously published reports on A. pigra, we found
      the diet composition to be similar to that of other Alouatta species (conforming
      to the folivore/frugivore profile), with 41% of feeding time spent eating fruit,
      45% foliage, and 11% flowers. This contrast may indicate a wide degree of dietary
      flexibility that allows A. pigra to inhabit a variety of habitat types. We
      suggest that a high level of resource abundance throughout the year makes the
      Community Baboon Sanctuary excellent habitat for Alouatta pigra.

PMID- 9651650
TI  - Use of sleeping trees by black and white colobus monkeys (Colobus guereza) in the
      Kakamega Forest, Kenya.
AB  - Groups of black and white colobus monkeys, or guerezas (Colobus guereza),
      observed in the Kakamega Forest, Kenya, had weak fidelity for sleeping sites.
      Groups often slept in trees near commonly used food sources, which might reduce
      the time and energetic costs of travel. Although the home range of each group
      overlapped with four to seven others, groups seemed to avoid sleeping near other
      groups, which would give them immediate and exclusive access to nearby food
      sources in the morning. The number of times a species of tree was slept in was
      positively correlated with its density. This may have occurred because so many
      suitable sites were available that proximity to feeding trees could be obtained
      whether or not groups slept in the feeding trees. Groups slept in tall trees,
      which provide stable sleeping sites and which may provide protection from both
      aerial and ground predators. Groups were more tightly clustered on nights with
      greater visibility, which might reduce the risk of predation.

PMID- 9651651
TI  - Topographical localization of iron in brains of the aged fat-tailed dwarf lemur
      (Cheirogaleus medius) and gray lesser mouse lemur (Microcebus murinus).
AB  - Iron deposits in the human brain are characteristic of normal aging but have also
      been implicated in various neurodegenerative diseases. Among nonhuman primates,
      strepsirhines are of particular interest because hemosiderosis has been
      consistently observed in captive aged animals. In particular, the cheirogaleids,
      because of their small size, rapid maturity, fecundity, and relatively short life
      expectancy, are a useful model system for the study of normal and pathological
      cerebral aging. This study was therefore undertaken to explore iron localization
      in the brain of aged cheirogaleids (mouse and dwarf lemurs) with histochemistry
      and magnetic resonance microscopy. Results obtained with both techniques were
      comparable. There was no difference between old animals in the two species. The
      young animals (3 years old) showed no iron deposits. In the old animals (8-15
      years old), iron pigments were mainly localized in the globus pallidus, the
      substantia nigra, the neocortical and cerebellar white matter, and anterior
      forebrain structures, including the nucleus basalis of Meynert. This distribution
      agrees with previous findings in monkeys and humans. In addition, we observed
      iron in the thalamus of these aged non-human primates. Microscopic NMR images
      clearly reveal many features seen with the histochemical procedure, and magnetic
      resonance microscopy is a powerful method for visualizing age-related changes in
      brain iron.

PMID- 9651652
TI  - Presence of platelet-activating factor in squirrel monkey (Saimiri boliviensis)
      spermatozoa: seasonal differences.
AB  - Platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphoryl-choline)
      (PAF) is a potent signaling phospholipid which has pleiotropic biological
      properties in addition to platelet activation. PAF has been detected in the
      spermatozoa in a number of species. The concentration of PAF is inversely related
      to human spermatozoa quality. There are no reports on the presence of PAF in
      nonhuman primate spermatozoa. Therefore, the primary objective of this study was
      to determine if PAF is present in the spermatozoa from the squirrel monkey (which
      is a seasonal breeder). A second objective was to determine if PAF levels change
      from the breeding to the nonbreeding season. Endogenous lipids were extracted
      from mature Bolivian squirrel monkeys (Saimiri boliviensis) spermatozoa and
      assayed for the presence of PAF by [125I] radioimmunoassay. PAF was detected in
      all samples assayed. PAF levels were significantly higher (P < 0.01) during the
      breeding season (mean: 3.58 ng/10(6) spermatozoa) than the nonbreeding season
      (mean: 0.76 ng/10(6) spermatozoa). The data demonstrate that PAF is present in
      squirrel monkey spermatozoa, with higher levels found during the breeding season.
      Additional studies are warranted to elucidate the role of PAF in spermatozoa
      function.

PMID- 9651653
TI  - Responses of gibbons (Hylobates lar) to their mirror images.
AB  - Nine gibbons (Hylobates lar) and one gibbon-siamang crossbreed were observed
      during exposure to their mirror images over two 30 minute baseline condition
      periods (mirror off) and four 30 minute treatment condition periods (mirror on).
      Greater frequencies and durations of gazing at the mirror and mirror-contingent
      behaviors were noted during the reflective conditions than for nonreflective
      conditions. Despite two subjects' apparent use of the mirror to view body parts
      otherwise not visible to them, no subjects passed a modified mark test. One
      subject exhibited limited aggressive displays toward the mirror, but no subjects
      exhibited abnormal behaviors in the presence of the mirror. The results expand on
      and confirm similar findings by Lethmate and Ducker [Zeitschrift fur
      Tierpsychologie 33:248-269, 1973].

PMID- 9651654
TI  - Sex-selection of human spermatozoa: evolution of current techniques and
      applications.
AB  - Methods claiming to achieve sex selection by sperm sorting have existed for many
      years. Numerous applications for safe and effective selection procedures exist in
      current clinical practice, as sex-linked conditions could be theoretically
      eliminated by use of appropriate sperm for fertilization or insemination. Use of
      such techniques could also address the need to effect family balancing for some
      couples. Modern preconception sex-selection methods may be classified into two
      general types: those that attempt to segregate spermatozoa on the basis of subtle
      physical or kinetic features, and those that rely on distinctive nuclear
      characteristics unique either to X- or Y-chromosome bearing sperm. Laboratories
      providing sperm sexing using the former method have been available for some
      years, although the associated efficiency and reproducibility are controversial.
      Sex selection of spermatozoa by chromatin differences has been shown to achieve
      significant enrichment of X- or Y-chromosome bearing sperm, but clinical
      experience in humans is limited. The fundamental elements of the two approaches
      introduced here are reviewed and compared. Selected key historical concepts in
      sex selection by sperm sorting are outlined, followed by a summary of promising
      areas for future research.

PMID- 9651655
TI  - Effect of clomiphene citrate on ovulation after treatment withdrawal.
AB  - The effect of clomiphene citrate (CC) on ovarian function in cycles subsequent to
      treatment withdrawal was studied. Thirty two out of 45 patients with anovulation
      due to polycystic ovarian syndrome (PCOS) and with no other factor affecting
      fertility who got pregnant were included. All patients received CC to induce
      ovulation. Pregnancies in CC treated cycles and after treatment were recorded.
      Twenty pregnancies were achieved during CC treated cycles and 12 in the cycles
      after it was withdrawn. In the latter group, eight pregnancies were achieved in
      the cycle following CC therapy, and four in the second subsequent cycle. In
      relation to pregnancy complications no significant statistical differences were
      found between the group of patients who became pregnant during the stimulation
      cycles and in the cycles after CC.

PMID- 9651656
TI  - Relation between bone mineral content and clinical, hormonal and biochemical
      parameters in postmenopausal women.
AB  - We studied factors related to bone mass after a natural or surgical menopause in
      73 healthy women attending the menopause clinic of a university hospital. In the
      natural menopause group we found inverse correlations between bone mineral
      density (BMD) vs. menopausal duration; BMD vs. body mass index (BMI) and BMI vs.
      inorganic phosphate (Pi), borderline correlations between weight vs. thyroxin
      (T4) and weight vs. luteinising hormone (LH) and a positive correlation between
      androstenedione (D4A) vs. urinary calcium (Uca). In the surgical menopause group
      we found some negative correlations (BMD vs. menopausal duration, BMI vs. Pi; BMI
      vs. dehydroepiandrosterone sulphate (DS), weight vs. DS and cortisol vs. Uca) and
      some positive correlations (BMD vs. free testosterone (fT), BMD vs. calcium (Ca),
      and BMD vs. Uca). We concluded that the serum hormone levels we measured were not
      useful markers of current bone mineral status.

PMID- 9651657
TI  - Human leucocyte antigens in pregnant women with pre-eclampsia associated with
      intrauterine growth retardation and in normal controls.
AB  - OBJECTIVE: To investigate the association between maternal HLA class II and
      intrauterine growth retardation with associated birthweight of the newborn, in
      women with preeclampsia. METHODOLOGY: Thirty preeclamptics and 30 normotensive
      matched for age, parity and gestation were investigated for HLA class II profile
      using Terasaki microlymphocytotoxicity test as the typing technique. The outcome
      of the pregnancy in terms of intrauterine growth retardation, birthweight and
      placental weight, were investigated to elucidate a susceptibility factor in the
      HLA Class II profile of the preeclamptic women. RESULTS: HLA class II DR2, DR4,
      DRw11, DRw14 and DQw2 were more common in the preeclamptic women (p < 0.04, 0.03,
      0.05, 0.03, 0.05), while DQw3 was more common in the controls (p < 0.05). Mean
      birthweight was 2.71 +/- 0.73 kg with preeclampsia compared to 3.4 +/- 0.4 kg for
      controls (p < O.01). Low birthweight was 56.7% versus 6.1% (p < 0.001) and mean
      placental weight was 474.8 +/- 100.8 gm versus 692.1 +/- 107.3 gm (p < 0.01). DR4
      and DQW2 were significantly associated with intrauterine growth retardation with
      associated low birthweight and placental weight (p < 0.01). CONCLUSION: HLA class
      II hyaplotypes DR4, and DQw2 are associated with intrauterine growth retardation
      with associated low birthweight and placental weight through preeclampsia. The
      association between intrauterine growth retardation and HLA may be a direct
      susceptibility factor. This needs further elucidation.

PMID- 9651658
TI  - Prognostic relevance of immunohistology, tumor size and vascular space
      involvement in axillary node negative breast cancer.
AB  - OBJECTIVE: Adjuvant treatment for patients with axillary node negative (ANN)
      breast cancer is controversial because operation alone gives a 70% cure rate.
      Features which predict recurrence are needed and we therefore evaluated the
      predictive value of tumor diameter and vascular involvement as well as of
      estrogen receptors (ER), progesterone receptors (PR), p53, MIB-1, c-erb and PCNA
      demonstrated by immunohistological staining in 178 patients with ANN breast
      cancer. Although ER status, tumor diameter and vascular space involvement were
      significantly correlated to the development of recurrence, their sensitivity,
      specificity and predictive value were too low to give them clinical value.

PMID- 9651659
TI  - Functional and phenotypic alterations in peritoneal macrophages from patients
      with early and advanced endometriosis.
AB  - The aim of this study was to elucidate whether peritoneal macrophage (pMO)
      alterations are a generalized feature in all stages of endometriosis and the
      effect of hormonal treatment on this leukocyte population. For this purpose we
      quantified the number of pMO, the expression of HLA-DR antigen (pMO DR+),
      percentages of pMO that reduced nitro-blue tetrazolium (pMO NBT+), and
      interleukin-1 (IL-1) and prostaglandin E2 (PGE2) production by pMO from patients
      with early (stages I/II) and advanced (stages III/IV) endometriosis, we also
      analyzed some of these properties in pMO from patients which had been treated for
      6 months with 800 mg/day of Danazol or gonadotropin releasing hormone agonist
      (GnRHa). We found that there were a significant increase of the pMO number in
      both types of patients, though the highest values were obtained in early
      endometriosis (p < 0.001). Percentages of pMO DR+ were decreased in all patients
      (p < 0.01) while percentages of pMO NBT+ were significantly increased. Production
      of IL-1 by early and advanced endometriosis pMO were considerably enhanced. PGE2
      release was not altered in early endometriosis pMO but, in advanced
      endometriosis, pMO PGE2 levels were 100-fold higher than control values. In
      posttreatment patients, the number of pMO and percentage of pMO NBT+ were similar
      to early endometriosis patients, though the percentage of pMO DR+ was within the
      normal range. We conclude that the pMO population, as well as IL-1 and PGE2
      production, were altered in all stages of endometriosis, and that these changes
      could be involved in the pathogenesis of endometriosis and associated
      infertility. Hormonal treatments do not reverse the pMO changes.

PMID- 9651660
TI  - Cancer associated serum antigen (CASA) levels in patients with breast carcinoma
      and in 3 control groups without breast cancer.
AB  - We have examined the predictive value of measurements of CASA (Cancer Associated
      Serum Antigen) levels in patients with breast carcinoma. The measurement uses
      monoclonal antibodies that bind to an epitope on the polymorphic epithelial
      mucin. CASA levels were of less value compared with the levels of other tumor
      markers (CA 15-3, CA 549 and CEA) in the management of patients with early breast
      cancer.

PMID- 9651661
TI  - Conjoined twin's cephalothoracopagus janiceps monoymmetros: a case report.

PMID- 9651662
TI  - The sympathetic skin response in peripheral autonomic failure--evaluation in pure
      failure, pure cholinergic dysautonomia and dopamine-beta-hydroxylase deficiency.
AB  - The sympathetic skin response (SSR) detects changes in the electrical potential
      in the skin in response to physiological and electrical stimuli and, therefore,
      may indicate the integrity of sympathetic cholinergic neural pathways to sweat
      glands. This has been evaluated in 21 patients with three forms of peripheral
      autonomic failure. Of these, 15 had pure autonomic failure (PAF) without
      additional neurological features; investigations indicated both sympathetic and
      parasympathetic failure. Four patients had pure cholinergic dysautonomia (PCD),
      with clinical and laboratory features indicating only cholinergic failure. Two
      siblings had dopamine-beta-hydroxylase (DBH) deficiency with only sympathetic
      adrenergic failure. None was on drugs affecting cholinergic function. Ten normal
      individuals were aged-matched with PAF patients and studied as controls. The SSR
      was recorded from the palmar hand and plantar foot surfaces, using previously
      described techniques, in response to physiological (auditory, cough and
      inspiratory gasp) and electrical stimuli. Nerve conduction studies excluded an
      associated motor or sensory neuropathy. The SSR was present in all normal
      individuals, and in both patients with DBH deficiency who had preserved
      cholinergic and sudomotor function, It was absent in all 15 PAF and all four PCD
      patients with impaired cholinergic function. Therefore, we conclude that the SSR
      reflected sympathetic cholinergic function in these three different groups with
      peripheral autonomic failure.

PMID- 9651663
TI  - QTc interval, and autonomic and somatic nerve function in diabetic neuropathy.
AB  - QTc intervals were measured using an electrocardiogram and other autonomic
      function tests, in 66 neuropathy patients with non-insulin-dependent diabetes
      mellitus (59.0 +/- 12.5 years; mean +/- SD). The change in R-R interval did not
      influence the QTc interval, as calculated by the equation: QTc = QT + (1000 - R
      R)/7 (ms), compared with the conventional Bazett's equation which appeared to
      overcompensate in the case of a small R-R interval. The QTc interval in the
      diabetic patients was significantly longer than that in age-matched controls. The
      QTc interval showed an inverse correlation with the coefficient of variation of
      the R-R interval and skin blood flow at rest. However, no correlation was found
      between QTc interval and blood pressure change, change in heart rate on standing,
      or results of the sympathetic skin response. The QTc interval did not correlate
      significantly with motor or sensory nerve conduction parameters. We conclude that
      the QTc interval can be a simple and useful autonomic indicator for diabetic
      neuropathy relatively independent of other abnormalities of autonomic and somatic
      nervous system function.

PMID- 9651664
TI  - Heart rate variability effects of an agonist or antagonists of the beta
      adrenoceptor assessed with scatterplot and sequence analysis.
AB  - There is evidence that the processes regulating heart rate variations reflect non
      linear complexity and show 'chaotic' determinism. Data analyses using non-linear
      methods may therefore reveal patterns not apparent with conventional statistical
      approaches. We have consequently investigated two non-linear methods, the
      Poincare plot (scatterplot) and cardiac sequence (quadrant) analysis, and
      compared these with standard time-domain summary statistics, during a normal
      volunteer investigation of an agonist and antagonists of the cardiac beta
      adrenoceptor. Under double-blind and randomized conditions (Latin square design),
      12 normal volunteers received placebo, celiprolol (beta 1- and beta 2
      adrenoceptor partial agonist), propranolol (beta 1- and beta 2-adrenoceptor
      antagonist), atenolol (beta 1-adrenoceptor antagonist) and combinations of these
      agents. Single oral doses of medication (at weekly intervals) were administered
      at 22:30 hours with sleeping heart rates recorded overnight. The long (SDNN,
      SDANN) and short-term (rmsSD) time-domain summary statistics were reduced by
      celiprolol--effects different from the unchanged or small increases after
      atenolol and propranolol alone. The Poincare plot was constructed by plotting
      each RR interval against the preceding RR interval, but unlike previous
      descriptions of the method, an automated computer method, with a high level of
      reproducibility, was employed. Scatterplot length and area were reduced following
      celiprolol and different from the small increases after propranolol and atenolol.
      The geometric analysis of the scatterplots allowed width assessment (i.e.
      dispersion) at fixed RR intervals. Differences between the drugs were confined to
      the higher percentiles (i.e. 75% and 90% of scatterplot length: low heart rate).
      The long-term time-domain statistics (SDNN, SDANN) correlated best with
      scatterplot length and area whereas the short-term heart rate variability (HRV)
      indices (rmsSD), pNN50) correlated strongly with scatterplot width. Cardiac
      sequence analysis (differences between three adjacent beats; delta RR vs delta
      RRn+1) assessed the short-term patterns of cardiac acceleration and deceleration,
      four patterns are identified: +/+ (a lengthening sequencing), +/- or -/+
      (balanced sequences), and finally -/- (a shortening sequence). A running count of
      events by quadrant, together with the average magnitude of the differences was
      computed. The beta-adrenoceptor partial agonist celiprolol increased acceleration
      sequences. The duration of beat-to-beat difference shortened after celiprolol;
      this contrasted with increased duration of beat-to-beat difference after
      propranolol and atenolol. These results demonstrated a shift towards sympathetic
      dominance after the beta-adrenoceptor partial agonist celiprolol contrasting in
      parasympathetic dominance after the beta-adrenoceptor antagonists propranolol and
      atenolol. These non-linear methods appear to be valuable tools to investigate HRV
      in health and in cardiovascular disease and to study the implications of
      alterations in autonomic control during therapeutic intervention.

PMID- 9651666
TI  - Effect of parasympathetic blockade on the signal-averaged electrocardiogram.
AB  - Low parasympathetic activity is associated with late potentials detected at a
      noise level of 0.4 microV in a signal-averaged electrocardiogram (SAECG)
      following myocardial infarction. In contrast, at a noise level of 0.2 microV,
      lowering parasympathetic activity influences late potential parameters in the
      opposite direction in healthy subjects. The aim of this study was to estimate the
      relationship between parasympathetic activity and the SAECG obtained at noise
      levels of 0.4 and 0.2 microV in healthy subjects. Two SAECG recordings in 10
      healthy subjects were obtained at noise levels of 0.2 and 0.4 microV before and
      after parasympathetic blockade using atropine (1 mg). Signal-averaged QRS
      duration (SA-QRS), late potential duration (LPD) defined as duration of terminal
      signals below 40 microV, and root mean square voltage of the terminal 40 ms of
      the averaged QRS (RMS40) were measured. At a noise level of 0.2 microV SA-QRS
      reduced from 124 +/- 14 to 114 +/- 17 ms (P = 0.008), LPD from 37 +/- 10 to 28 +/
      14 ms (P = 0.01), and RMS40 increased from 26 +/- 22 to 41 +/- 25 microV (P =
      0.006) during parasympathetic blockade compared to baseline values. At a noise
      level of 0.4 microV the SA-QRS (115 +/- 15 ms) and LPD (29 +/- 11 ms) were lower
      and the RMS40 (37 +/- 23 microV) was higher compared to the noise level 0.2
      microV, and no systematic alterations of the three variables were found during
      parasympathetic blockade. The parasympathetic nervous system may induce a very
      low-amplitude late potential in the SAECG. The data suggest that parasympathetic
      activity and a low noise level may lead to a false late potential-positive SAECG
      in low arrhythmia risk subjects. Therefore, we recommend the use of a noise level
      of 0.4 microV or identification of high arrhythmia risk patients by late
      potential and low parasympathetic activity.

PMID- 9651665
TI  - Effect of a 'vagomimetic' atropine dose on canine cardiac vagal tone and
      susceptibility to sudden cardiac death.
AB  - We manipulated the level of cardiac vagal tone in dogs with healed myocardial
      infarctions during exercise plus acute ischemia, to explore vagal involvement in
      the pathophysiology of sudden cardiac death. We occluded the circumflex coronary
      artery during the last minute of treadmill exercise in 32 dogs with healed
      anterior myocardial infarctions. Twenty-one dogs experienced ventricular
      fibrillation (susceptible) and 11 did not (resistant). On a subsequent day, we
      gave intravenous low-dose atropine to susceptible dogs to increase their levels
      of cardiac vagal tone, as estimated by moving polynomial time-series analysis of
      R-R interval variability (0.24-1.04 Hz). We also measured vagal responses to
      coronary occlusion at rest, before and after low-dose atropine. In susceptible
      dogs, atropine increased the average vagal tone index at rest (atropine: 7.3 +/-
      0.4 versus control: 6.6 +/- 0.5 ln ms2, P < 0.01) and during maximum exercise
      (atropine: 2.5 +/- 0.4 versus control: 1.6 +/- 0.3 ln ms2, P < 0.01), but failed
      to prevent ventricular fibrillation actually decreased from 63 +/- 3 to 42 +/- 2s
      (P < 0.01), and R-R interval shortening elicited by coronary occlusion increased
      (atropine: delta -144 +/- 64 versus control: delta -55 +/- 32 ms, P < 0.01). In
      resting susceptible dogs, atropine significantly increased preocclusion indexes
      of vagal tone (atropine: 7.8 +/- 0.3 versus control: 6.9 +/- 0.4 ln ms2, P <
      0.01), but did not prevent large reductions of vagal tone during ischemia
      (atropine: delta -4.4 +/- 0.6 versus control: delta -3.8 +/- 0.4 ln ms2, P >
      0.05). We conclude that increases of resting vagal tone after low-dose atropine
      in dogs with healed anterior myocardial infarctions do not protect against sudden
      cardiac death. Quite the contrary, vagal tone is withdrawn more completely during
      ischemia, and the time to ventricular fibrillation during exercise plus ischemia
      is shortened.

PMID- 9651667
TI  - Distribution of cardiovascular related cells within the human thalamus.
AB  - Representation of cardiovascular function has not been investigated in the human
      thalamus. In the rat, the insular cortex is the principal forebrain site of
      cardiovascular representation whose afferents originate from a circumscribed
      thalamic area (nucleus ventralis posterolateralis-parvicellular portion, VPLpc).
      We therefore evaluated 4481 thalamic cells for phasic cardiovascular activity
      using extracellular recording techniques in 60 unanesthetized patients undergoing
      neurosurgical procedures. We identified 26 cells with phasic activity strongly
      related to the cardiac cycle in 10 patients. These cells clustered within the
      ventrocaudal nucleus of the thalamus (the principal sensory nucleus analogous to
      the ventral posterior thalamic group in the rat and monkey) and were equally
      distributed between the right and left sides. The majority of these cells (17/26)
      showed peaks of phasic neuronal activity within 50 ms of the peak systolic
      pressure; 35% had peripheral cutaneous fields in areas to which cardiac pain is
      often referred. We suggest that these cells may be involved in the integration of
      afferent baroreceptor information; may possibly be concerned with the generation
      and/or processing of central cardiac pain in humans; and that their derangement
      may possibly contribute to the lethal cardiovascular disturbances which occur in
      fatal familial insomnia.

PMID- 9651668
TI  - Short-term variability of blood pressure and heart rate in hyperthyroidism.
AB  - The effect of hyperthyroidism on the short-term memory variability of blood
      pressure and heart rate was evaluated in 12 untreated hyperthyroid patients
      during thyrotoxicosis and after a 6 1/2 month treatment designed to achieve a
      stable euthyroid state. Beat-by-beat finger blood pressure was measured with a
      Finapres device. The pulse interval, from which pulse rate was derived, was
      obtained from the blood pressure signal. Due to the significant change in heart
      rhythm associated with thyrotoxicosis, both pulse interval (taken as a surrogate
      of heart period) and pulse rate (taken as a surrogate of heart rate) were
      computed. Power spectral analysis showed a reduction in the overall heart period
      variability in the supine position in the hyperthyroid compared to the euthyroid
      state. This effect was observed in the low-frequency (0.005-0.068 Hz), mid
      frequency (0.068-0.127 Hz) and high-frequency (respiratory) domains as well, with
      a significant reduction of the modulus of these bands of 31%, 35% and 47%,
      respectively. The heart rate spectral modulus also exhibited a reduction of the
      high-frequency component (31%) in the supine position in the hyperthyroid
      subjects. These changes in heart rhythmicity corroborate a vagal deficit in
      hyperthyroidism. In addition, blood pressure spectral power exhibited a
      significant deficit in the orthostatism-induced mid-frequency systolic blood
      pressure rise in the hyperthyroid state (64%) compared with the euthyroid state.
      This observation may reflect a reduced vascular sympathetic activation with
      standing. The resulting vasodilatation could well contribute to normalize blood
      pressure in thyrotoxicosis in which cardiac output is increased.

PMID- 9651669
TI  - Bacterial chemotaxis: unsolved mystery of the flagellar switch.
AB  - Impressive progress has been made in understanding the mechanism of bacterial
      chemotaxis and function of the flagellar motor, but how the direction of rotation
      is reversed by the 'flagellar switch'--a central step in chemotaxis--remains
      obscure and calls for new experimental approaches.

PMID- 9651670
TI  - Transcriptional control: Tat cofactors and transcriptional elongation.
AB  - HIV-1 gene expression requires the transactivator Tat, which stimulates viral
      transcript elongation. Recent results show that two cellular cyclin-dependent
      kinases, which phosphorylate the carboxy-terminal domain of the RNA polymerase II
      large subunit, contact Tat and contribute to the control of transcriptional
      elongation.

PMID- 9651671
TI  - Ion channels: a first view of K+ channels in atomic glory.
AB  - Crystal structures have been solved for the transbilayer pore domain of a
      bacterial K+ channel and the tetramerisation domain of voltage-gated K+ channel.
      These provide our first real structural insights into possible mechanisms of ion
      selectivity and permeation for K+ channels.

PMID- 9651672
TI  - Proteasome assembly: biting the hand.
AB  - Proteasome assembly is regulated to ensure the enzyme is inactive until its
      active sites are compartmentalized within an interior aqueous chamber. In yeast,
      this depends on a dedicated chaperone that is trapped within the nascent
      proteasome, and degraded on maturation of the proteolytic subunits.

PMID- 9651673
TI  - Cell-mediated immunity: the role of bacterial protein secretion.

PMID- 9651674
TI  - Meiosis: step-by-step through sporulation.
AB  - A transcription factor, Ndt80p, has been identified that has a critical role in
      the pathway that controls meiosis--sporulation--in budding yeast. Ndt80p
      coordinately controls genes that mediate spore formation and progression through
      the two meiotic divisions; it may also be a target of a checkpoint control.

PMID- 9651675
TI  - Molecular chaperones: clamps for the Clps?
AB  - The Clp/Hsp100 molecular chaperones are unusual in their ability to tease apart
      protein aggregates and complexes. Recent results make a good case that these
      chaperones bind substrates via PDZ-like domains; this may reflect a general
      strategy for manipulating the] assembly state of substrate proteins.

PMID- 9651676
TI  - Protein folding: a missing redox link in the endoplasmic reticulum.
AB  - Native disulphide-bond formation during protein folding in the endoplasmic
      reticulum requires oxidative machinery, the components and mechanism of which are
      not yet fully understood. Two recent papers have identified a novel protein
      component that appears to play a key role in this important redox pathway.

PMID- 9651677
TI  - The pleckstrin homology domain of oxysterol-binding protein recognises a
      determinant specific to Golgi membranes.
AB  - BACKGROUND: Peripheral membrane proteins are targeted to the cytoplasmic face of
      specific intracellular membranes. The organelle-specific ligands recognised by
      peripheral proteins include other proteins and lipids. Oxysterol-binding protein
      (OSBP) translocates from the cytoplasm to the Golgi apparatus on binding
      oxygenated derivatives of cholesterol. The mechanism by which OSBP recognises the
      Golgi is unknown. It does, however, contain a pleckstrin homology (PH) domain,
      which in other proteins has been found to mediate regulated membrane binding,
      although in all previously studied examples the binding is to the plasma
      membrane. RESULTS: The PH domain of OSBP and of a yeast homologue, Osh1p, were
      sufficient to target proteins specifically to mammalian Golgi membranes. In
      addition, high level expression disrupted Golgi architecture and prevented
      forward traffic of cargo protein. In vitro, the OSBP PH domain bound to Golgi
      membranes in a manner apparently dependent on phosphatidylinositol-4,5
      bisphosphate (PI(4,5)P2) or a related phosphatidylinositide. The OSBP PH domain
      bound to PI(4,5)P2 in liposomes with a submicromolar dissociation constant.
      CONCLUSIONS: The PH domains of OSBP and its yeast homologue recognise a
      determinant which is specific to Golgi membranes and important for Golgi
      function. The determinant appears to be a combination or a phosphatidylinositol
      polyphosphate and a second, Golgi-specific feature.

PMID- 9651678
TI  - Calcium triggers calcineurin-dependent synaptic vesicle recycling in mammalian
      nerve terminals.
AB  - BACKGROUND: Following exocytosis at the synapse, synaptic vesicle components are
      recovered by endocytosis. Morphological analysis has suggested that this occurs
      by a clathrin-mediated pathway, and the GTPase dynamin is thought to be involved
      in 'pinching off' endocytosing vesicles. The finding that the calcium-dependent
      phosphatase calcineurin can dephosphorylate dynamin and two other proteins
      implicated in endocytosis (amphiphysin and synaptojanin) has suggested a
      potential role for calcium and dephosphorylation in regulating synaptic vesicle
      endocytosis. RESULTS: We tested this hypothesis with an endocytosis assay in
      isolated nerve terminals (synaptosomes) that relies on the use of the fluorescent
      dye FM2-10. In synaptosomes, vesicle recycling occurs predominantly via a pathway
      dependent on both dynamin and amphiphysin. We found that endocytosis could be
      stimulated maximally at calcium concentrations that yielded only low levels of
      exocytosis, suggesting that the two processes had different calcium sensitivities
      cyclosporin A and Fk506, we identified calcineurin as a calcium sensor for
      endocytosis and showed that its activity is essential for synaptic vesicle
      endocytosis in synaptosomes. CONCLUSIONS: Our results suggest that dynamin
      dependent synaptic vesicle endocytosis is triggered by calcium influx occurring
      upon nerve-terminal depolarisation. An essential mediator of calcium's effect is
      calcineurin, the activation of which leads to dephosphorylation of at least four
      proteins implicated in endocytosis-dynamin, amphiphysin 1, amphiphysin 2 and
      synaptojanin. Our findings also imply that endocytosis and exocytosis may occur
      in tandem in vivo simply because they share a responsiveness to calcium influx,
      rather than because they are mechanistically coupled.

PMID- 9651679
TI  - The regulation of Cdc20 proteolysis reveals a role for APC components Cdc23 and
      Cdc27 during S phase and early mitosis.
AB  - BACKGROUND: In eukaryotic cells, a specialized proteolysis machinery that targets
      proteins containing destruction-box sequences for degradation and that uses a
      ubiquitin ligase known as the anaphase-promoting complex/cyclosome (APC) plays a
      key role in the regulation of mitosis. APC-dependent proteolysis triggers the
      separation of sister chromatids at the metaphase-anaphase transition and the
      destruction of mitotic cyclins at the end of mitosis. Recently, two highly
      conserved WD40-repeat proteins, Cdc20 and Cdh1/Hct1, have been identified as
      substrate-specific regulators for APC-dependent proteolysis in the budding yeast
      Saccharomyces cerevisiae. Here, we have investigated the cell cycle regulation of
      Cdc20 and Cdh1/Hct1. RESULTS: Whereas the levels CDH1/HCT1 RNA and Cdh1/Hct1
      protein are constant throughout the cell cycle, CDC20 RNA and Cdc20 protein are
      present only during late S phase and mitosis and Cdc20 protein is unstable
      throughout the entire cell cycle. The instability of Cdc20 depends on CDC23 and
      CDC27, which encode components of the APC. During the G1 phase, a destruction box
      within Cdc20 mediates its instability, but during S phase and mitosis, although
      Cdc20 destruction is still dependent on CDC23 and CDC27, it does not depend on
      the Cdc20 destruction box. CONCLUSIONS: There are remarkable differences in the
      regulation of Cdc20 and Cdh1/Hct1. Furthermore, the APC activator Cdc20 is itself
      a substrate of the Cdc27 have a role in the degradation of Cdc20 during S Phase
      and early mitosis that is not mediated by its destruction box.

PMID- 9651680
TI  - Probing the role of homomeric and heteromeric receptor interactions in TGF-beta
      signaling using small molecule dimerizers.
AB  - BACKGROUND: Transforming growth factor Beta (TGF-Beta) arrests many cell types in
      the G1 phase of the cell and upregulates plasminogen activator inhibitor 1 (PAI
      1). The type 1 (TGF-Beta RI) an II (TGF-Beta RII) TGF-Beta receptors mediate
      these and other effects of TGF-Beta on target cells. TGF-Beta initially binds to
      TGF-Beta RII and subsequently TGF-Beta RI is recruited to form a heteromeric
      complex. TGF-Beta RI phosphorylates the downstream effectors Smad2 and Smad3,
      leading to their translocation into the nucleus. Here, we explored the role of
      receptor oligomerization in TGF-Beta signaling. RESULTS: We constructed fusion
      proteins containing receptor cytoplasmic tails linked to binding domains for
      small-molecule dimerizers. In COS-1 cells, recruitment of a soluble TGF-Beta RII
      tail to a myristoylated TGF-Beta RI tail promoted Smad2 nuclear translocation. In
      mink lung cells, homo-oligomerization of a myristoylated TGF-Beta Ri tail in
      presence of a myristoylated TGF-Beta RII tail activated the PAI-1 promoter.
      Oligomerization of an acidic mutant of the TGF-Beta RI tail in absence of TGF
      Beta RII activated the PAI-A promoter and inhibited the growth of mink lung
      cells. CONCLUSIONS: Non-toxic, small molecules designed to oligomerize
      cytoplasmic tails of TGF-Beta receptors at the plasma membrane can activate TGF
      Beta signaling. Although TGF-Beta normally signals through two receptors that are
      both necessary for signaling, in one small-molecule system, a dimerizer activates
      signaling through a single type of receptor that is sufficient to induce TGF-Beta
      signaling. These methods of activating TGF-Beta signaling could be extended to
      signaling pathways of other TGF-Beta superfamily members such as activin and the
      bone morphogenetic proteins.

PMID- 9651681
TI  - Indirect evidence for Delta-dependent intracellular processing of notch in
      Drosophila embryos.
AB  - Cell-cell signaling mediated by the receptor Notch regulates the differentiation
      of a wide variety of cell types in invertebrate and vertebrate species, but the
      mechanism of signal transduction following receptor activation is unknown. A
      recent model proposes that ligand binding induces intracellular processing of
      Notch; the processed intracellular form of Notch then translocates to the nucleus
      and interacts with DNA-bound Suppressor of Hairless (Su(H)), a transcription
      factor required for target gene expression. As intracellular processing of
      endogenous Notch has so far escaped immunodetection, we devised a sensitive
      nuclear-activity assay to monitor indirectly the processing of an engineered
      Notch in vivo. First, we show that the intracellular domain of Notch, fused to
      the DNA-binding domain of Gal4, regulated transcription, in a delta-independent
      manner. Second, we show that full-length Notch, containing the Gal4 DNA-binding
      domain inserted 27 amino acids carboxy-terminal to the transmembrane domain,
      activated transcription in a delta-dependent manner. These results provide
      indirect evidence for a ligand-dependent intracellular processing event in vivo,
      supporting the view that Su(H)-dependent Notch signaling involves intracellular
      cleavage, and transcriptional regulation by processed Notch.

PMID- 9651682
TI  - The Pristionchus pacificus mab-5 gene is involved in the regulation of ventral
      epidermal cell fates.
AB  - One system that can be used to study the evolution of gene function is the
      nematode vulva. In Caenorhabditis elegans, the vulva is formed from three of the
      six multipotent precursors P(3-8).p. Comparison of vulval development between C.
      elegans and Pristionchus pacificus has revealed that, during evolution, there
      have been changes in the specification of cell fate for certain vulval cells. For
      example, the cell P8.p is a vulval precursor cell (VPC) in C. elegans, but is
      incompetent to adopt vulval fate in P. pacificus We have fate specification and
      have isolated P. pacificus mutants with a second vulva-like structure in the
      posterior region resulting from the ectopic differentiation of P8.p Genetic and
      molecular analysis indicated that point mutations in the Hox-cluster gene mab-5
      of P. pacificus cause this multivulval phenotype. Further cell ablation studies
      revealed that the differentiation of P8.p is independent of gonadal signaling. In
      C. elegans, mab-5 also acts in P8.p specification, but mab-5 mutant animals do
      not develop differs between species, indicating that alterations in the intrinsic
      properties of P8.p and corresponding changes in the functional specificity of mab
      5 have occurred during evolution.

PMID- 9651684
TI  - Conversion of zebrafish blastomeres to an endodermal fate by TGF-beta-related
      signaling.
AB  - The endoderm contributes cells to the gut, and participates in the induction and
      patterning of the vertebrate head and heart. The mechanisms controlling the
      formation of endoderm are poorly understood. Commitment of endoderm cells occurs
      at the onset of gastrulation and requires cell interactions; studies in vitro
      have implicated transforming growth factor Beta (TGF-beta)-related molecules in
      this process. TARAM-A is a zebrafish receptor kinase that is related to the type
      I subunit of the TGF-beta receptor, and is expressed in presumptive
      endomesodermal cells at gastrulation. We provide here evidence for its
      involvement in endoderm formation in vivo. Activation of TARAM-A was found to
      drive blastomeres towards an endodermal fate. The induced endoderm behaved ad
      endogenous endoderm during gastrulation: it migrated in contact with the yolk and
      expressed endoderm-specific markers. Loss-of-function mutations in the zebrafish
      one-eyed-pinhead (OEP) gene lead to defects in heart formation, defects of the
      ventral central nervous system (CNS) and cyclopia. Mutant embryos also lack
      endoderm and anterior mesoderm. Endoderm formation in oep mutant embryos was
      found to be restored by the activation of the TARAM-A signaling pathway. Cardiac
      and ocular defects, but not midline CNS structures, were rescued non
      autonomously, demonstrating that endoderm may provide signals that can pattern
      the eye anlage, and which are distinct form those specifying the ventral midline
      of the CNS.

PMID- 9651683
TI  - The kit receptor promotes cell survival via activation of PI 3-kinase and
      subsequent Akt-mediated phosphorylation of Bad on Ser136.
AB  - The c-kit-encoded receptor protein tyrosine kinase for stem cell factor (Kit/SCF
      R) is essential for the development of cells within the hematopoietic,
      melanogenic and gametogenic lineages. SCF stimulation induces activation of
      phosphatidylinositol (PI) 3-kinase, which is required for SCF-induced mitogenesis
      and cell survival, and for activation of the serine/threonine, we found that, in
      response to SCF Akt became activated and mediated phosphorylation of Bad, a pro
      apoptotic molecule, in a PI-3-kinase-dependent manner. Phosphorylation of Bad was
      restricted to Ser112 and Ser136 in vivo, but only the Akt phosphorylation sit
      Ser136 was essential for SCF-promoted cell survival. Furthermore, Bad and Akt
      interacted and colocalized in intact cells. A Kit/SCF-R gain-of-function mutant
      that has increased mitogenic and PI 3-kinase activation potential, due to the
      absence of the two protein kinase C negative feedback phosphorylation site,
      enhanced both Akt activation and Bad phosphorylation and also resulted in
      increased cell survival. Such a mechanism may account for how deregulated PI 3
      kinase activity and naturally occurring gain-of-function point mutants of Kit/SCF
      R lead to cellular transformation and fatal malignancies in man.

PMID- 9651685
TI  - Sif2p interacts with Sir4p amino-terminal domain and antagonizes telomeric
      silencing in yeast.
AB  - Several regions of the Saccharomyces cerevisiae genome are subject to position
      dependent transcriptional repression mediated by a multi-component nucleosome
      binding complex of silent information regulator proteins (Sir2p, Sir3p and
      Sir4p). These proteins are present in limiting amounts in the nucleus and are
      targeted to specific chromosomal regions by interaction with sequence-specific
      DNA-binding factors. Different sites of repression compete for Sir complexes,
      although it is not known how Sir distribution is regulated. In a screen for
      factors that interact with Sir4p amino terminus, we have cloned SIF2, which
      encodes a WD40-repeat-containing factor that disrupts telomeric silencing when
      overexpressed. In contrast to deletion of SIR4, SIF2 deletion improved telomeric
      repression, suggesting that under normal conditions Sif2p antagonizes Sir4p
      function at telomeres. Sif2p overexpression altered the subnuclear localization
      of Sir4p, but not its protein expression level, suggesting that Sif2p may recruit
      Sir4p to nontelomeric sites or repression. The sif2 mutant strains were
      hypersensitive to a range of stress conditions, but did not have decreased
      viability and did not alter repression in the rDNA. In conclusion, Sif2p
      resembles the Sir4p regulatory proteins Sir1p and Uth4p in that it competes for
      the functional assembly of Sir4p at telomeres, yet unlike Sir1p or Uth4p, it does
      not target Sir4p to either mating-type or rDNA loci.

PMID- 9651686
TI  - Service development to meet the needs of 'people with communication disabilities'
      in developing countries.
AB  - PURPOSE: In spite of the catastrophic consequences of impaired communication
      skills on the quality of human life, development of services for people with
      communication disabilities have low priority in health care and rehabilitation.
      Nowhere is this more apparent than in developing countries. The low coverage
      levels of the limited services which do exist in these countries, indicate a need
      to develop new and innovative service structures. It is to this end, given the
      limited literature available, that this review looks mainly at articles of a
      descriptive nature based on clinical experience. The review seeks to identify
      ideology which could be used to under-pin alternative service delivery and
      structures. METHOD: Three collections of literature relevant to the topic under
      discussion are identified, one collection relates to impairment categories, one
      to disability perspectives and one to speech and language therapy provision. It
      is recognized that all three collections are needed to form a basis for
      innovative change, but this review aims to examine the latter collection only,
      referring the reader to items in the other collections, when relevant. RESULTS:
      The information reviewed is analysed for recurring themes and the results are
      seen to concur with many of the disability perspectives expressed in present day
      literature.

PMID- 9651687
TI  - Effects of a multidisciplinary rehabilitation programme on health-related quality
      of life in patients with prolonged musculoskeletal disorders: a 6-month follow-up
      of a prospective controlled study.
AB  - PURPOSE: The aim of this prospective, controlled, follow-up study (6 months) was
      to examine the effects of a multidisciplinary rehabilitation programme on
      perceived health-related quality of life (HRQL) in patients with prolonged
      musculoskeletal disorders (PMSD). The programme focused on body awareness therapy
      and cognitive and relaxation treatment. METHOD: The rehabilitation group
      comprised 122 patients, and there were 114 patients in the matched control group
      (CG). Both groups of patients had access to primary health care. Baseline data
      were compared with 6-month follow-up data within and between the groups. The
      following measurements were employed: HRQL (Nottingham Health Profile), body
      awareness, postural control, pain (VAS), pain-related medicine consumption,
      isometric arm muscle endurance, aerobic capacity, psychosomatic symptoms,
      physical and psychosocial working environment and sick leave. RESULTS: Variables
      that improved significantly as compared with the CG were: HRQL, anxiety, pain
      related to movements, psychosomatic symptoms and need for pain-related medicines.
      CONCLUSIONS: The multidisciplinary rehabilitation programme used here improved
      HRQL in patients with PMSD to a greater extent than the standard treatment
      provided within primary heath care (p = 0.01) at least in the short term.

PMID- 9651688
TI  - Hospital-based rehabilitative care versus outpatient services: effect on
      functioning and health status.
AB  - PURPOSE: The goal of this clinical trial was to examine the long-term impact of
      rehabilitative care on the health status of patients diagnosed with a disabling
      disorder. METHOD: Study patients consisted of first-time hospitalizations from
      diagnostic groups commonly admitted for inpatient rehabilitation, including
      nervous, circulatory, and musculoskeletal disorders or injury. Patients were
      randomly assigned to inpatient rehabilitation (n = 43) or to outpatient follow-up
      (n = 42) in which the usual medical services were provided but no scheduled
      rehabilitative therapies were offered. Specific objectives of the study were to
      determine the effects of impatient rehabilitation on: (1) functional ability, (2)
      health and mental health status, (3) personal adjustment, and (4) family
      function. Cost and use of health-care resources were descriptively assessed.
      RESULTS: Analysis of covariance found no significant treatment effects, either at
      6 months or at 1 year, for any of the variables under study. In addition, there
      were no differences between groups in their use of nursing homes, length of
      hospital stay, mortality, or in the number of hospital readmissions or clinic
      visits during the first year after hospital discharge. Use of rehabilitation
      services and cost of care was significantly higher than outpatient services. The
      findings were consistent with previous studies for most outcomes, with the major
      exception being functional improvements. Contrary to earlier studies,
      rehabilitation was not found to effectively produce lasting functional outcomes.
      However, study conditions may not have fully corresponded to those of previous
      studies, and further research is needed. The patient sample was representative of
      a full inpatient service and therefore more heterogeneous than samples reported
      in prior studies, but the small sample size (due to reductions in the number of
      admitted patients to the rehabilitation unit during the course of the study)
      precluded subgroup analysis of diagnostic groupings. CONCLUSION: The findings
      suggest that hospital-based rehabilitative care does not have lasting benefits,
      and that alternative care or supportive follow-up by a subacute-care facility may
      be needed to assist patients in maintaining functional gains and health benefits.

PMID- 9651689
TI  - Percutaneous endoscopic gastrostomy in neurological rehabilitation: a report of
      six cases.
AB  - PURPOSE: This study reports the cases of six patients with severe chronic
      neurological disability and swallowing difficulties due to traumatic brain injury
      (TBI), anoxia and multiple sclerosis (MS). METHOD: The patients required
      nutritional supplement through percutaneous endoscopic gastrostomy (PEG).
      RESULTS: Their clinical follow-up showed a decrease of intercurrent medical
      complications, especially pressure sores. In addition, an improvement of
      oropharyngeal function was observed in some patients, also accompanied by
      slightly better basic psychomotor functions such as vigilance, sustained
      attention and tone or motor control. However, not every patient did improve with
      this procedure. The two MS patients benefited most, while the improvement was
      less homogenous in the three TBI patients. CONCLUSIONS: The advantages of PEG
      over nasogastric tube on oropharyngeal function can be related to the absence of
      pharyngeal irritation and its role in overall recovery could be due to an
      increase in social activities, a control of infections, a better rehabilitation
      schedule and a long-term effect on brain function due to better nutritional
      support.

PMID- 9651690
TI  - Re: Clinical commentary. Disability and rehabilitation.

PMID- 9651691
TI  - Associated EMG responses to voluntary hand movement in probable Alzheimer's
      disease.
AB  - The goal of this work is to dilucidate the mechanism that yields the associated
      EMG responses in patients with probable Alzheimer's disease. Seventeen subjects
      fulfilling this criteria and ten normal subjects as a control group were
      selected. They were asked to perform an oddball task in which they had to
      discriminate between two kinds of stimuli and produce a response to one of them.
      Results show that reaction times in controls and in patients when there is no
      associated EMG are equal in latency. When the associated EMG response occurs in
      the pathological group reaction time is significantly increased. Furthermore, the
      associated EMG response is delayed in 55 milliseconds when compared to the
      voluntary movement. Although these results may reflect some controversy, we
      interpret this finding as a contralateral inhibitory deficit associated to the
      corpus callosum abnormalities that occur in the evolving course of Alzheimer's
      disease.

PMID- 9651692
TI  - Visual evoked potentials in hypothyroidism: a long-term evaluation.
AB  - Visual Evoked Potentials (VEP) were measured in 9 new-diagnosed hypothyroid
      female patients--mean age 46 +/- 12 ys--before treatment, during (with monthly
      evaluations) thyroid hormone replacement therapy and after long-term therapy, at
      the achievement as well as one year after having achieved and maintained
      euthyroidism. Three of the hypothyroids had abnormally prolonged latencies (m.v.
      131.7 +/- 7.9 ms), while 7 had lower than normal amplitude (m.v. 2.3 +/- 2.8
      microV). No remarkable change of amplitude was observed after the achievement of
      euthyroidism, after a mean time of 5.9 +/- 4.9 months (range 2-14 months). A
      significant shortening of latency (m 128.3 +/- 7.6 ms), even still higher than
      the control value (m 122.7 +/- 3.7 ms) was found. Significant correlation between
      P100 latency and thyroid hormone levels was found for TT4 (r = 0.3353; p =
      0.005), TT3 (r = 0.2568; p = 0.032) and FT4 (r = 0.3572; p = 0.002). No further
      improvement in P100 latency (m 129.5 +/- 7.2 ms; p = 0.037) was found one year
      after the achievement of euthyroidism, while a remarkable amplitude increase (m
      9.2 +/- 3.4 micro; p = 0.001) was observed. Our findings indicate that, as well
      as other studied parameters, VEP are reversibly alterated in hypothyroidism,
      probably in relation to metabolic rather than to structural alterations.
      Moreover, VEP can represent a useful neurophysiologic parameter for quantitation
      of SNC involvement in hypothyroidism.

PMID- 9651693
TI  - Electrophysiological study of myoclonus in pediatric practice.
AB  - Myoclonus can be caused from a variety of central nervous system disorders. With
      regard to its pathophysiology, much work has been done in adult patients, but
      reports from pediatric clinics are scarce. We describe the clinical and
      electrophysiological features of four different types of myoclonus in children
      using back averaging technique. In a patient with cortical reflex myoclonus,
      myoclonic jerks were induced in the distal right arm by taps on the ipsilateral
      fingers. Myoclonus was preceded by the cortical spike which was localized
      posterior to the central sulcus contralateral to the myoclonus, and the cortical
      spike was time-locked to the myoclonus. In a patient with subcortico-cortical
      myoclonus, myoclonus occurred as a focal motor seizure. Myoclonic jerks were
      preceded by generalized cortical waves which were of maximal amplitude over the
      cortex contralateral to the myoclonus, and cortical waves time-locked to the
      myoclonus. A patient with spinal myoclonus had rhythmical and segmental
      myoclonus. Myoclonus was induced in both arms after electrical stimulation at the
      wrist with a latency which was slightly longer than that of the F wave. In a
      patient with brainstem myoclonus, muscle activity was bilaterally synchronous and
      was predominant in the proximal flexors. The pattern of muscle recruitment
      suggested that the myoclonus signal travelled downward along the spinal cord and
      upward through the brainstem. The back averaging technique is essential in the
      differential diagnosis of myoclonus.

PMID- 9651694
TI  - Electromyographic evaluation of the rectus femoris muscle during exercises
      performed on the leg press.
AB  - The rectus femoris was analysed in 10 volunteers during knee flexion and
      extension with the feet in normal, plantar flexion and dorsal flexion positions.
      Hewlett-Packard surface electrodes, an electromyographic signal amplifier, a
      computer equipped with an A/D conversion plaque (Model CAD 10/26), software
      specially designed to record and analyse the signals, Horizontal Leg Press, and
      electrogoniometers were used. The rectus femoris muscle showed strong potentials
      at the beginning of knee extension. In the simultaneous bending of the knee and
      hip the activity was strong toward the end of the movement. The rectus femoris
      showed a similar activity both in the upper and lower platforms. As for foot
      positions, the rectus femoris showed the smallest potentials with the foot in
      plantar flexion and the largest ones with the foot in dorsal flexion.

PMID- 9651695
TI  - Effect of nerve block on sural amplitude during remote muscle contraction.
AB  - We previously reported that the median sensory nerve action potentials (SNAPs)
      increased in amplitude during both near (3) and remote (4) muscle contraction.
      The objective of the present project was to begin to study the pathway by which
      this occurred. The sural amplitude was measured after one min. of isometric
      biceps contraction and compared pre and post lidocaine nerve block in 10 healthy
      subjects. The baseline was defined as the least amount of current needed to
      elicit a minimal sural response pre contraction. This level of stimulus remained
      constant throughout the experiment. Results showed that the sural amplitude
      peaked 4 min. after muscle contraction. An 8.1 microV increase in sural amplitude
      from baseline was noted pre injection as 5 min. post contraction, and an increase
      of 13.4 microV was noted comparing pre to post injection amplitudes at the same
      time. Statistical analysis using two-way interaction comparing the time courses
      pre and post injection showed a 92% chance the responses were dissimilar Post hoc
      least significant difference (LSD) analyses were significant at 4 min. (p = .005)
      and 6 min. (p = 0.29) post contraction. In conclusion, the increase in sural
      amplitude after remote muscle contraction was no longer apparent after proximal
      sural nerve block. This suggests that the nerve itself is required in the final
      common pathway for the transmission of this induced signal.

PMID- 9651696
TI  - Quantitative study of Stewart-Holmes test.
AB  - Stewart-Homes test (SHT) is an ordinary neurological test performed for the
      diagnosis for cerebellar disease. We developed a quantitative method based on SHT
      carried out on the upper limb. Nineteen cerebellar patients and fifteen volunteer
      healthy subjects were tested. During the test, acceleration of forearm and two
      associated surface EMGs over biceps and triceps brachialis were recorded and
      analyzed. (1) Acceleration curve showed an oscillating pattern with flexion and
      extension over the elbow in both groups, but in cerebellar patient group, the
      acceleration oscillation wave was more pronounced and latencies of peak
      acceleration were significantly longer. (2) Correspondingly, the EMGs timing
      parameters were also different between the two groups: in patient group, ceasing
      isometric biceps contraction was delayed; rebound EMGs bursts over both biceps
      and triceps were prolonged. (3) Modelization of the oscillation of acceleration
      curve with dampened oscillation model showed that in patient group the
      oscillating amplitude attenuated much more slowly than in control group. A
      standard curve was established for detecting the acceleration profile
      abnormalities of SHT in cerebellar patients.

PMID- 9651697
TI  - Event-related potentials in the segmental exclusion syndrome of the upper limb.
AB  - Upper limb segmental exclusion syndromes are frequent after traumatic or
      infectious affections. They can be defined as an insufficient utilization of a
      limb segment--fingers or hand--reversible on verbal exhortation and arising in
      subjects with no other neurologic or psychiatric disorder. Our hypothesis was
      that the segmental exclusion syndrome could be likened to a neglect behavior. To
      verify the validity of this hypothesis, we measured digital nerve short-latency
      SEP and SEP-P300 waves in response to odd-ball task target stimuli in healthy
      volunteers (n = 11) and patients with digit exclusion syndromes (n = 19). For N20
      latency, there was no significant difference (Wilcoxon's test: p = 0.52) between
      normal and excluded digits. Stimulation of the excluded vs normal digit resulted
      in a significant lengthening in SEP-P300 latency (p = 0.0003). The implication of
      these results and means of extending our knowledge of the pathophysiology of
      exclusion syndromes are discussed.

PMID- 9651698
TI  - The abductor pollicis brevis R1 response: normative data and physiological
      behavior.
AB  - BACKGROUND: Although H reflexes cannot be reliably recorded from resting human
      hand intrinsic muscles, a short latency R1 response, thought to be similar to the
      H reflex, is readily obtained from upper extremity muscles during voluntary
      contraction. METHODS: The right and left median nerves of 20 normal subjects were
      repetitively stimulated at 3 Hz at stimulus intensities corresponding to
      threshold and 20%, 40% and 60% of maximal M response, recording from the abductor
      pollicis brevis muscle. Studies were done during both minimal and moderate
      voluntary contraction. RESULTS: The R1 response was present in all subjects at
      the 40% stimulation intensity level during moderate contraction. The mean latency
      was 27 ms (SD 1.77 ms) with a good correlation to arm length. The mean amplitude
      was 1.17 mV (SD 0.79 mV). CONCLUSIONS: Abductor pollicis muscle R1 response can
      be reliably measured, although latency showed much less intersubject and side to
      side variability than amplitude. This technique may be useful for the assessment
      of demyelinative lesions of the inferior segments of the brachial plexus and C8
      T1 roots.

PMID- 9651699
TI  - Low molecular weight heparins in acute coronary syndromes.

PMID- 9651700
TI  - Sleep apnoea: a therapeutic target in congestive heart failure.

PMID- 9651701
TI  - Time delays in starting thrombolytic therapy.

PMID- 9651702
TI  - Trans-septal catheterization: a new frontier in clinical electrophysiology?

PMID- 9651703
TI  - Evaluation of chest pain in women.

PMID- 9651704
TI  - Cardiothoracic ratio and relative heart volume as predictors of coronary heart
      disease mortality.

PMID- 9651705
TI  - Pushing the ablation frontier in atrioventricular node reentrant tachycardia.

PMID- 9651706
TI  - Overview of studies of exercise training in chronic heart failure: the need for a
      prospective randomized multicentre European trial.

PMID- 9651707
TI  - Should we screen for asymptomatic left ventricular dysfunction to prevent heart
      failure?
AB  - A programme to detect and treat asymptomatic left ventricular dysfunction would
      seem to fulfil all five principles of screening. Indeed, such a programme would
      appear to be at least as firmly based as those already in existence for, for
      example, cervical and breast cancer. Further evaluation of the screening of high
      risk groups to detect asymptomatic left ventricular systolic dysfunction with the
      aim of giving treatment to prevent the development of heart failure is merited.

PMID- 9651708
TI  - Assessment of tissue viability: clinical demand and problems.

PMID- 9651709
TI  - Cardiothoracic ratio and relative heart volume as predictors of coronary heart
      disease mortality. The Whitehall study 25 year follow-up.
AB  - AIM: To examine the association of radiographic measures of heart size with
      mortality from coronary heart disease. METHODS AND RESULTS: One thousand, one
      hundred and ninety-one male civil servants aged 40-69 years were followed-up for
      mortality over 25 years in relation to cardiothoracic ratio and relative heart
      volume. A high cardiothoracic ratio and relative heart volume predicted coronary
      (n = 196 deaths) and all-cause mortality, but not respiratory or malignant
      mortality. After adjustment for age, systolic and diastolic blood pressure, the
      highest (> or = 0.47) compared to the lowest quintile of the cardiothoracic ratio
      (< 0.40) was associated with a rate ratio of 1.84 (95% CI 1.14-2.97) for the
      effect on coronary heart disease mortality. Further adjustment for heart rate,
      smoking, cholesterol, angina and ECG ischaemia had little effect, reducing the
      rate ratio to 1.65 (95% CI 1.01-2.70). Similar rate ratios were observed for
      relative heart volume. CONCLUSIONS: Cardiothoracic ratio within the range
      considered 'normal' in clinical practice predicted coronary heart disease
      mortality independent of established coronary heart disease risk factors. The
      relative heart volume, which uses measurements from the lateral as well as the
      posteroanterior chest X-ray, did not predict coronary heart disease any better
      than the cardiothoracic ratio. The extent to which left ventricular mass and
      systolic dysfunction-- pathophysiological correlates of the cardiothoracic ratio
      and relative heart volume--are independent risk factors for coronary heart
      disease should be further investigated.

PMID- 9651710
TI  - Lesion morphology assessed by pre-interventional intravascular ultrasound does
      not predict the incidence of severe coronary artery dissections.
AB  - AIMS: Coronary artery dissections are common findings following percutaneous
      transluminal coronary angioplasty and occur with an incidence of approximately
      20% to 40%. The purpose of this study was to evaluate the impact of intravascular
      ultrasound for the prediction of severe dissections by pre-interventional
      analysis of lesion morphology and plaque composition. METHODS AND RESULTS: Pre-
      and post-interventional intravascular ultrasound was performed in 197 patients
      with 205 lesions. Using intravascular ultrasound criteria, 24 lesions were
      classified as soft (hypo- or iso-echogenic), 73 as intermediate (hyper-echogenic)
      and 108 as calcified (calcific arc > 90 degree of the vessel circumference).
      Additionally, calcium localization was defined as subendothelial, central or
      deep. The incidence of dissections was 37.5% in patients with soft lesions, 24.7%
      in patients with intermediate and 36.1% in patients with calcified lesions. In
      calcified lesions, the occurrence of severe dissections was not dependent on the
      localization of calcium deposits. The procedural parameters were similar in all
      patients. The minimal inflation pressure, however, was significantly higher in
      calcified lesions (P < 0.01). CONCLUSION: Assessment of lesion morphology by
      intravascular ultrasound cannot predict the occurrence of severe dissections
      following percutaneous transluminal coronary angioplasty. Furthermore, despite
      significantly higher inflation pressures in heavily calcified lesions, the
      incidence of dissections was found to be comparable in all lesions.

PMID- 9651712
TI  - Delays in thrombolytic therapy for acute myocardial infarction in Finland.
      Results of a national thrombolytic therapy delay study. Finnish Hospitals'
      Thrombolysis Survey Group.
AB  - OBJECTIVE: To determine lengths and causes of pre- and in-hospital delays in
      thrombolytic treatment. DESIGN: A prospective national survey covering 48 of the
      51 Finnish university, central and general hospitals to obtain basic data before
      the start of a public campaign to shorten patient-related delay in acute
      myocardial infarction. SUBJECTS: One thousand and twelve consecutive patients
      with acute myocardial infarction who received thrombolytic therapy over 3 months
      in 1995 and who represent 40% of all patients with confirmed acute myocardial
      infarction. RESULTS: The median interval between onset of infarction symptoms and
      initiation of thrombolytic therapy was 160 min (30-647). Only 13% of the patients
      received thrombolysis within 60 min and 38% within 120 min. The median time from
      the onset of symptoms to the call for help was 60 min (5-491), and no difference
      was found in patients with or without a history of previous myocardial infarction
      (60 and 64 min, respectively). Only 52% of the patients called to the dispatch
      centre. The median delay from calling for help to hospital arrival was 40 min (10
      170). The median in-hospital door-to-needle thrombolysis delay was 40 min (12
      196). In 13% of hospitals the median delay was more than 60 min. The emergency
      physician encountered difficulties in decision making in 33% of cases.
      CONCLUSIONS: Only 38% of the patient received thrombolysis within 2 h of onset of
      symptoms. Patient-related delay before they sought help accounted for the major
      portion of the total treatment delay. Thus the findings emphasize the importance
      of prompt action when people are confronted with an acute heart attack.
      Reorganizing the emergency medical service and emergency department routines is
      also a necessary target to shorten thrombolysis delays. The delay attributable to
      transporting patients could be shortened by initiating thrombolytic treatment in
      the pre-hospital setting. In Finnish hospitals, door-to-needle delay was
      acceptable in cases with clear indications for thrombolysis. However, emergency
      physicians often had diagnostic difficulties, which led to remarkably longer in
      hospital delays.

PMID- 9651711
TI  - The 60 Minutes Myocardial Infarction Project. Characteristics on admission and
      clinical outcome in patients with reinfarction compared to patients with a first
      infarction.
AB  - PURPOSE: The purpose of the study was to evaluate parameters that characterize
      patients with myocardial reinfarction as compared to patients with a first
      infarction in clinical practice, and possibly to determine their clinical
      outcome. METHODS: The 60 minutes Myocardial Project is a German multicentre
      prospective observational study in which 136 hospitals are participating.
      Fourteen thousand, nine hundred and eighty consecutive patients with acute Q wave
      myocardial infarction were included from July 1992 to September 1994. RESULTS:
      Out of these 14,980 patients, there were 2854 (19%) with reinfarction and 12,126
      (81%) with a first infarction. Patients with a reinfarction arrived at the
      hospital 24 min earlier than patients with a first infarction (pre-hospital delay
      156 vs 180 min; P < 0.001); the door-to-needle time with reinfarction was longer
      (38 vs 30 min; P < 0.001); however, patients with reinfarction were older (69 vs
      66 years; P < 0.001), had a lower rate of a diagnostic first ECG (54 vs 71%; P <
      0.001) and received thrombolytic therapy less frequently than patients with a
      first infarction (46 vs 52%; P < 0.001). A low number of patients received
      primary PTCA ( n = 205) since only a few hospitals offered a primary PTCA service
      at the time the study was performed. In patients with reinfarction, there were
      more reasons as to why thrombolytic therapy was not given (24 vs 21%; P < 0.001).
      Left bundle branch block occurred more frequently in patients with reinfarction
      (15 vs 8%; P < 0.001). The intra-hospital course in patients with reinfarction
      was associated with an increase of complications and intra-hospital death (23 vs
      15%; P < 0.001. CONCLUSIONS: Although reinfarction patients arrived earlier at
      hospital than patients with a first infarction, the former received thrombolytic
      therapy less frequently than the latter. Patients with reinfarction were older,
      more frequently had a non-diagnostic ECG on admission and had a higher rate of
      contraindications against thrombolytic therapy.

PMID- 9651713
TI  - Frequency and prognostic implications of conduction defects in acute myocardial
      infarction since the introduction of thrombolytic therapy.
AB  - OBJECTIVE: To document the frequency of conduction defects and their influence on
      prognosis in a large series of patients with acute myocardial infarction who
      underwent coronary care during a period when thrombolytic therapy was in common
      usage. BACKGROUND: Conduction defects have been associated with an adverse
      prognosis following acute myocardial infarction, but there are few data on the
      incidence and outcome of conduction defects since the introduction of
      thrombolytic therapy. PATIENTS AND METHODS: The study group comprised 1225
      consecutive patients with acute myocardial infarction treated in the coronary
      care unit from 1 January 1988 to 31 December 1994. Conduction defects were
      recorded prospectively and were classified as follows: complete atrioventricular
      node block associated with narrow complex escape rhythms; left or right bundle
      branch block; bifascicular block; complete heart block involving both bundle
      branches. RESULTS: Electrocardiographic data were available in 1220 patients.
      Complete atrioventricular node block occurred in 65 (5.3%), left and right bundle
      branch block in 29 (2.4%) and 44 (3.6%) bifascicular block in 36 (2.9%) and
      complete heart block involving both bundle branches in 20 (1.6%). The more
      advanced degrees of block in the bundle branches occurred more commonly in
      patients with diabetes, previous infarction. Q-wave infarction, anterior
      infarction and left ventricular failure. Survival analysis showed an increased
      short- and long-term cardiac mortality in patients with conduction defects,
      prognosis worsening as the severity of the conduction defect increased.
      CONCLUSION: Conduction defects complicated acute myocardial infarction in 16% of
      cases and had a graded impact on the short- and long-term prognosis, patients
      with advanced bundle branch involvement faring worst. The data showed a small
      decline in the rate of severe conduction defects compared with previous studies,
      possibly reflecting the beneficial effects of thrombolytic therapy on infarct
      size.

PMID- 9651714
TI  - Unstable coronary artery disease in post-menopausal women. Identifying patients
      with significant coronary artery disease by basic clinical parameters and
      exercise test. IRIS Study Group.
AB  - BACKGROUND: The diagnostic information from an ECG taken while at rest and an
      exercise test is considered less reliable in women than in men, mostly due to a
      high percentage of false-positive tests. This can be explained by a lower pre
      test likelihood of coronary heart disease. AIMS: To evaluate the diagnostic
      information that can be gained from basic clinical parameters, an ECG and
      exercise test in a group of post-menopausal women with symptoms of unstable
      coronary artery disease in order to identify patients with significant coronary
      artery stenoses. METHODS AND RESULTS: We prospectively studied 200 post
      menopausal women admitted to the coronary care unit with symptoms of unstable
      coronary artery disease and ECG changes suggestive of ischaemia. The diagnostic
      value of common risk factors, myocardial enzymes and an early exercise test were
      assessed. A coronary angiogram was performed within 60 days. Median age was 67
      years. On admission, 38% had ST depression on an ECG taken while at rest, 76% had
      T-wave inversion, and 41% increased enzyme levels. The coronary angiogram
      revealed that 15% had no atherosclerosis, 14% had atherosclerosis but not lesion
      > or = 50% of luminal diameter and 71% had at least one significant stenosis. Of
      patients with known indicators of atherosclerotic disease, all but one had
      atherosclerosis visualized on the coronary angiogram. A relative ST depression >
      or = 0.1 mV and a low maximum workload at exercise test were strong predictors of
      significant coronary artery disease. The positive predictive value of ST
      depression was 91% and of low maximum workload 84% CONCLUSION: In post-menopausal
      women with signs of unstable angina and ischaemia on an ECG taken while at rest,
      the prevalence of coronary atherosclerosis is high, 85%. Contrary to earlier
      studies, ST T-changes at the early exercise test had a high positive predictive
      value, especially in combination with a low maximum workload with no false
      positive results.

PMID- 9651715
TI  - Predictors of left ventricular thrombus formation and disappearance after
      anterior wall myocardial infarction.
AB  - AIMS: This study sought to determine predictors of left ventricular thrombus
      formation and resolution after acute anterior wall myocardial infarction. METHODS
      AND RESULTS: We have analysed clinical, echocardiographic and angiographic data
      in 53 consecutive patients with anterior myocardial infarction. Two-dimensional
      and Doppler echocardiographic examinations were performed on days 1, 2, 3 and 7,
      after 3 and 6 weeks, and 3, 6, and 12 months following infarction. Coronary
      angiography was performed in 44 patients before hospital discharge. Left
      ventricular thrombus was detected in 30/53 patients (29/30 in the first week
      after infarction). Univariate analysis showed that left ventricular thrombus
      formation was associated with a higher initial end-systolic volume index (beta =
      0.04, P = 0.001), and end-diastolic volume index (beta = 0.03, P = 0.03), a
      larger infarct perimeter (beta = 0.02, P = 0.01), a lower initial ejection
      fraction (beta = 0.06, P =0.001), a higher initial wall motion score index (beta
      = 1.75, P = 0.023), a higher peak creatine kinase level (beta = 3.90, P = 0.01),
      Killip class >1 (beta = 1.11, P = 0.003), infarct expansion (beta = 0.78, P =
      0.04), occluded infarct-related artery (beta = -0.87, P = 0.04) and non
      thrombolytic therapy (beta = -0.76, P = 0.047). According to the Cox proportional
      regression model, independent predictors of thrombus formation after anterior
      myocardial infarction were high end-systolic volume index (beta = 0.06, P =
      0.001) and high peak creatine kinase level (beta = 5.17, P = 0.046). Thrombus
      disappeared in 11/30 (36.7%) patients during one-year echocardiographic follow
      up. The only independent predictor of thrombus disappearance after acute
      myocardial infarction was the absence of apical dyskinesis 6 weeks after
      infarction (beta = -1.53, P = 0.045). CONCLUSIONS: Our data demonstrate that the
      best predictor of left ventricular thrombus formation after acute anterior
      myocardial infarction is a high initial end-systolic volume. Thrombus resolution
      is more likely to occur in patients without apical dyskinesis at the end of the
      healing phase of infarction.

PMID- 9651716
TI  - Direct percutaneous transluminal coronary angioplasty in acute myocardial
      infarction. Predictors of short-term outcome and the impact of coronary stenting.
      Study Group of The Arbeitsgemeinschaft Leitender Kardiologischer Krankenhausarzte
      (ALKK).
AB  - BACKGROUND: Direct percutaneous transluminal coronary angioplasty (PTCA) is
      widely accepted in the treatment of acute myocardial infarction since excellent
      results had been reported from several small randomized trials. Less favourable
      results were observed in large-scale registries. In particular, the use of stents
      in acute myocardial infarction has become common practice without documented
      evidence of clinical efficacy. METHODS: Data were analysed from a registry of all
      consecutive percutaneous transluminal coronary angioplasty procedures from 62
      centres in Germany, including 2331 direct percutaneous transluminal coronary
      angioplasty in acute myocardial infarction from July 1994 to April 1997. RESULTS:
      The overall angiographic success rate of percutaneous transluminal coronary
      angioplasty, defined as complete antegrade perfusion of the infarct vessel, was
      87%. In-hospital mortality was 11.2%. The most important predictor of death was
      the presence of cardiogenic shock in 15% of patients, of whom 52% died. Mortality
      in patients without shock was 3.9%. Failed percutaneous transluminal coronary
      angioplasty was associated with a mortality of 36%. Further independent
      predictors of death were older age, multivessel disease, and anterior myocardial
      infarction. Stents were used in 4.1% of the procedures in 1994, increasing to 53%
      in 1997. However, this was not accompanied by improved clinical outcome.
      Mortality with coronary stenting was 9.9% vs 11.6% without stents (ns).
      CONCLUSIONS: Direct percutaneous transluminal coronary angioplasty is a valuable
      treatment strategy in acute myocardial infarction, although the results are less
      exceptional than reported from some highly specialized centres. Failed
      percutaneous transluminal coronary angioplasty seems to be harmful, thus
      outweighing much of the benefit from successful procedures. Stents did not
      improve the clinical outcome significantly, despite technically successful
      placement in 98%. Mortality from cardiogenic shock continues to be excessively
      high despite direct PTCA.

PMID- 9651717
TI  - Effect of oxygen on sleep quality, cognitive function and sympathetic activity in
      patients with chronic heart failure and Cheyne-Stokes respiration.
AB  - BACKGROUND: Cheyne-Stokes respiration disrupts sleep, leading to daytime
      somnolence and cognitive impairment. It is also an independent marker of
      increased mortality in heart failure. This study evaluated the effectiveness of
      oxygen therapy for Cheyne-Stokes respiration in heart failure. METHODS: Eleven
      patients with stable heart failure and Cheyne-Stokes breathing were studies.
      Oxygen and air were administered for 4 weeks in a double-blind, cross-over study.
      Sleep and disordered breathing was assessed by polysomnography. Symptoms were
      assessed using the Epworth Sleepiness Scale, visual analogue and quality of lift
      scores. Cognitive function was assessed by neuropsychometric testing. Overnight
      urinary catecholamine excretion was used as a measure of sympathetic nerve
      activity. RESULTS: Ninety-seven percent of apnoeas were central in origin. Oxygen
      therapy reduced the central apnoea rate (18.4 +/- 4.1 vs 3.8 +/- 2.1 per hour; p
      = 0.05) and periodic breathing time (33.6 +/- 7.4 vs 10.7 +/- 3.9% of actual
      sleep time; p = 0.003). Oxygen did not improve sleep quality, patient symptoms or
      cognitive failure. Oxygen reduced urinary noradrenaline excretion (8.3 +/- 1.5 vs
      4.1 +/- 0.6 nmol.mmol-1 urinary creatinine; p = 0.03). CONCLUSION: Oxygen
      stabilized sleep disordered breathing and reduced sympathetic activity in
      patients with heart failure and Cheyne-Stokes respiration. We were unable to
      demonstrate an effect on either patient symptoms or cognitive function.

PMID- 9651718
TI  - Fast pathway ablation in patients with common atrioventricular nodal reentrant
      tachycardia and prolonged PR interval during sinus rhythm.
AB  - AIMS: This study aimed to clarify the safety and efficacy of selective fast
      pathway ablation in patients with atrioventricular nodal reentrant tachycardia
      and a prolonged PR interval during sinus rhythm. Such patients have been reported
      to have an increased incidence of complete atrioventricular block. METHODS AND
      RESULTS: In this study, the earliest retrograde atrial activation during
      atrioventricular nodal reentrant tachycardia and right ventricular stimulation
      was localized. Fast pathway ablation was then performed in five patients with the
      common form of atrioventricular nodal reentrant tachycardia and a prolonged PR
      interval. Three of the five patients had almost incessant atrioventricular nodal
      reentrant tachycardia. Radiofrequency catheter ablation induced a complete
      ventriculo-atrial block during right ventricular stimulation in four patients and
      a marked prolongation of ventriculo-atrial conduction during right ventricular
      stimulation in one. Non-inducibility of common atrioventricular nodal reentrant
      tachycardia with and without isoproterenol was achieved in all five patients. The
      PR interval increased from 254 +/- 53 ms to 276 +/- 48 ms and the atrio-His
      interval from 172 +/- 46 ms to 192 +/- 45 ms. Second- or third-degree
      atrioventricular block did not occur during the ablation procedure. During the
      followup of 19 +/- 20 months none of the patients developed symptoms suggestive
      of atrioventricular nodal reentrant tachycardia or evidence of second- or third
      degree atrioventricular block. CONCLUSION: These data suggest that
      atrioventricular node (retrograde) fast pathway ablation can apparently be safely
      performed in patients with common atrioventricular nodal reentrant tachycardia
      and a prolonged PR interval during sinus rhythm.

PMID- 9651719
TI  - Permanent junctional re-entry tachycardia. A multicentre long-term follow-up
      study in infants, children and young adults.
AB  - AIMS: Permanent junctional re-entry tachycardia is a relatively uncommon form of
      re-entry tachycardia with antegrade conduction occurring through the
      atrioventricular node and retrograde conduction over an accessory pathway usually
      located in the postero-septal region. It was the aim of the study to investigate
      the course of permanent junctional re-entry tachycardia with particular regard to
      the effectiveness of pharmacological treatment and ablation procedures;
      evaluation was performed with respect to the patient's symptoms, tachycardia
      rate, frequency of the tachycardia and left ventricular function. METHODS AND
      RESULTS: The long-term follow-up of 32 patients with permanent junctional re
      entry tachycardia was evaluated. The first presentation with supraventricular
      tachycardia occurred between the 27th week of gestation and 27 years. The
      tachycardia rate ranged from 100 to 250 beats.min-1. During Holter-ECG, permanent
      junctional re-entry tachycardia was documented as present for over 50% of the
      time in 24 h in 22 patients (69%). Left ventricular performance was impaired in
      nine patients (28%) due to a tachycardia-related cardiomyopathy. Symptoms or
      signs of heart failure were mild to moderate in eight and severe in four
      patients; 20 patients showed no clinical impairment. Follow-up time was 1 to 31
      (mean 10) years; current age of the patients ranged from 1.5 months to 35 (mean =
      15 x 3) years. Four patients needed no therapy because of the infrequency of
      permanent junctional re-entry tachycardia episodes. Twenty-five patients
      initially received antiarrhythmic drugs, which were effective or partially
      effective in 14 (56%). Eight of them are still on medical therapy; in five
      treatment was discontinued because of absence of symptoms. Eleven patients had
      ablation of the accessory pathway during follow-up, three underwent ablation as a
      primary procedure. CONCLUSION: Permanent junctional re-entry tachycardia in our
      experience is an arrhythmia with a large variety of clinical symptoms. Patients
      with a slow tachycardia rate and infrequent episodes of tachycardia may never
      develop symptoms and therefore do not need any therapy. Patients with frequent
      permanent junctional re-entry tachycardia, a fast tachycardia rate and impaired
      left ventricular function need effective therapy. In infancy and early childhood
      medical therapy is recommended as a first option, whereas in older and
      symptomatic patients catheter ablation is an effective and safe procedure.

PMID- 9651720
TI  - Trans-septal catheterization for radiofrequency catheter ablation of cardiac
      arrhythmias. Results and safety of a simplified method.
AB  - AIM: This study reports on the results and safety of a simplified method of trans
      septal catheterization for radiofrequency catheter ablation of cardiac
      arrhythmias. METHODS AND RESULTS: Over 5 years, 411 patients underwent trans
      septal catheterization for radiofrequency catheter ablation: 388 patients had a
      left-sided accessory pathway, 19 a left-sided focal atrial tachycardia, two
      atrial fibrillation and two post-infarction ventricular tachycardia. All but one
      patient with ventricular tachycardia underwent elective trans-septal
      catheterization. In the absence of a patent foramen ovale, puncture of the atrial
      septum was performed by using an 8F Mullins sheath and a Brockenbrough needle,
      according to the simplified method described in this paper. Trans-septal
      catheterization was accomplished in 383/388 patients (98.7%); in 41 patients a
      second trans-septal catheterization and radiofrequency catheter ablation was
      performed for initial failure or recurrence. Radiofrequency catheter ablation was
      successful in 96% of accessory pathway patients, 90% of atrial tachycardia
      patients, in both patients with atrial fibrillation and in both patients with
      ventricular tachycardia. No complication related to trans-septal catheterization
      was observed. CONCLUSION: In experienced hands and according to the method
      described in this paper, the elective use of transseptal catheterization for
      radiofrequency catheter ablation in a large cohort of patients with cardiac
      arrhythmias is feasible, safe and allows successful ablation in the vast majority
      of the patients.

PMID- 9651721
TI  - Impact of dietary sodium intake on left ventricular diastolic filling in early
      essential hypertension.
AB  - AIMS: Dietary sodium intake modulates left ventricular hypertrophy in established
      essential hypertension independent of blood pressure level. We conducted this
      study to elucidate the relationship between sodium intake and left ventricular
      structural or functional changes in early essential hypertension. METHODS: Forty
      four young male patients (age 25.9 +/- 2.6 years) with mild essential
      hypertension that had never been treated and 45 normotensive male control
      subjects of similar age were examined. Dietary sodium intake was measured from 24
      h urinary sodium excretion, blood pressure from 24 h ambulatory monitoring
      (SpaceLabs 90207), left ventricular structure from 2-D guided M-mode
      echocardiography, and diastolic filling of the left ventricle (as the main
      compound of diastolic function in a young population) by pulse-wave Doppler
      sonography. RESULTS: In hypertensive patients, daily sodium excretion correlated
      with the ratio of late (A) to early (E) maximum velocity (A/E; r = + 0.27, P =
      0.07), velocity time integrals (A/E; r = + 0.54, P < 0.001) as well as atrial
      contribution, as a percent of left ventricular filling (VH ATCO; r = + 0.52, P <
      0.001) independent of heart rate, whereas the opposite correlations were observed
      in normotensive (all P < 0.001). Stepwise multiple regression analysis confirmed
      these results. Sodium excretion emerged as the strongest independent determinant
      of impaired diastolic filling in hypertensive patients (velocity time integrals
      A/E: R(2) = 0.49, beta = 0.57, P = 0.0001; VH ATCO: R(2) = 0.48, beta = + 0.56, P
      < 0.0001; Vmax A/E: ns). In normotensive subjects, sodium excretion was a similar
      strong, but inverse determinant of diastolic filling (velocity time integrals
      A/E: R(2) = 0.40, beta = -0.43, P = 0.0028). Heart rate was a strong determinant
      of diastolic filling in hypertensive patients (beta = +0.55, P = 0.0002) and in
      normotensive subjects (beta = + 0.34, P = 0.011). Left ventricular mass and end
      diastolic volume index were not related to diastolic filling in either group.
      CONCLUSION: In early essential hypertension, sodium excretion is correlated with
      impaired left ventricular diastolic filling independent of left ventricular mass.
      The renin-angiotensin-aldosterone-aldosterone system might be a mediator of the
      observed correlation.

PMID- 9651722
TI  - Segmental comparison between coronary angiography and positron emission
      tomography reveals low predictive value of epicardial flow for viability.
AB  - BACKGROUND: The functional significance of the anterograde and retrograde filling
      of coronaries on angiography is controversial. METHODS AND RESULTS: Eighteen
      patients with 27 severe lesions (> 85% diameter stenosis) after previous
      extensive myocardial infarction were selected. The left ventricle was divided
      into 33 segments for regional comparison of epicardial flow (as assessed by
      angiography) and tissue perfusion as well as metabolism (as measured by 13NH3-
      and 18FDG-PET). Viability was defined as normal perfusion (> 80% relative of
      maximum 13NH3 activity) or mismatch defect (> 1.2 metabolism/flow ratio). A
      method has been developed to register the 'lesion predicted region', determined
      on the basis of angiography, in the same polar map as derived from the positron
      emission tomography data. Distal to the lesion, the anterograde epicardial flow
      was evaluated by Thrombolysis in Myocardial Infarction (TIMI) criteria (TIMI flow
      0-3), and retrograde filling was graded on a 0-3 scale (collateral grade 0-3).
      TIMI flow grade and retrograde collateral grade in every lesion predicted region
      segment were summed to indicate the total segmental epicardial flow. Out of the
      594 segments, 369 were associated with a severe lesion. Among them, significantly
      higher average perfusion and metabolic activities were found in segments of good
      epicardial filling (summed epicardial flow > or = 3) than in the territories of
      limited epicardial flow (summed score < 3): 65.4 +/- 17% vs 45.6 +/- 10 (P =
      0.001%) and 68.6 +/- 16% vs 47.4 +/- 11% (P = 0.0004), respectively. However,
      when we analysed the predictive value of angiographically detectable good
      epicardial flow for positron emission tomography viability criteria then the
      positive predictive value was found to be as low as 0.5, while the negative
      predictive value was considerably higher (0.82). CONCLUSION: After myocardial
      infarction, angiographically detectable limited epicardial flow reveals scarred
      segments while good epicardial contrast filling does not necessarily indicate
      maintenance of nutritive function.

PMID- 9651723
TI  - Impaired diastolic suction during coronary angioplasty.

PMID- 9651724
TI  - Harmful effect of enalapril on left ventricular remodelling in patients without a
      severe residual stenosis after acute anterior wall infarction?

PMID- 9651725
TI  - Serum lactate dehydrogenase activity: indicator of the development of pneumonitis
      induced by amiodarone.

PMID- 9651726
TI  - Arginine consumption in coronary disease.

PMID- 9651727
TI  - An association of an antibody against Chlamydia pneumoniae and coronary heart
      disease observed in Japan.

PMID- 9651728
TI  - Catecholamines: the cardiovascular and neuroendocrine system.
AB  - The development of profound autonomic dysfunction and of neuroendocrine
      activation characterizes and possibly contributes to the progression of heart
      disease to congestive heart failure. Sympathetic activation is a generalized
      process and the proposed mechanisms for neurohumoral activation include decreased
      input from excitatory afferences and increased input from excitatory chemoceptors
      and metabaroceptor. These phenomena vary to a great extent in different subjects:
      in the more impaired patients, renal and cardiac overflow of catecholamines can
      increase three- and ten-fold, respectively, accounting for about 60% of the
      increase of noradrenaline in congestive heart failure. Efficient methods to
      quantify sympathetic cardiovascular influences and neuroendocrine indices have
      been developed and it has been recognized that sympathoneural activation
      independently predicts the survival of patients. The pathophysiological role and
      the clinical relevance of neuroadrenergic abnormalities also constitute the
      grounds for the understanding of the therapeutic benefit obtained with
      interventions aimed at mitigating the harmful consequences of adrenergic
      hyperactivity.

PMID- 9651729
TI  - Methods to quantify sympathetic cardiovascular influences.
AB  - This paper will critically review the main features of the various techniques
      (plasma noradrenaline assay, noradrenaline spillover technique, microneurographic
      recording of postganglionic muscle sympathetic nerve and power spectral analysis
      of blood pressure and heart rate signals in specific bands) currently employed to
      assess sympathetic cardiovascular control in humans. After highlighting the
      advantages and limitations of each approach, the paper will describe some of the
      results obtained by employing the above mentioned techniques to detect
      abnormalities in sympathetic cardiovascular tone in physiological and
      pathological conditions.

PMID- 9651730
TI  - Effect of sympathetic overactivity on cardiovascular prognosis in hypertension.
AB  - Increased sympathetic tone is found in about 30% of patients with hypertension.
      This abnormality is closely associated with the metabolic syndrome of
      dyslipidaemia and hyperinsulinaemia. In this short review we discuss the
      mechanisms by which sympathetic over-activity could cause the metabolic syndrome.
      Sympathetic stimulation enhances cardiac and vascular hypertrophy. Left
      ventricular hypertrophy is a strong predictor of poor cardiovascular outcomes.
      Hypertrophy of resistance vessels accelerates hypertension, whereas hypertrophy
      of smaller coronary vessels limits coronary reserve and increases tendency for
      coronary spasms. Epidemiologically, high haematocrit is associated with
      hypertension and is recognized as an independent coronary risk factor.
      Sympathetic stimulation increases haematocrit through an increase of post
      capillary vascular resistance. Sympathetic over-activity is also associated with
      platelet activation which may further add to the risk of coronary thrombosis in
      neurogenic hypertension. Tachycardia, which is due to increased sympathetic and
      deceased parasympathetic tone, is a hallmark of neurogenic hypertension. Fast
      heart rate is a strong predictor of coronary events and sudden death. The
      mechanisms by which tachycardia increases the cardiovascular risk are outlined.

PMID- 9651731
TI  - Relevance of heart rate as a prognostic factor in patients with acute myocardial
      infarction: insights from the GISSI-2 study.
AB  - AIMS: It is as yet undefined whether simple indexes of autonomic balance such as
      heart rate (HR) may play a role in risk stratification in patients with acute
      myocardial infarction (MI). The aim of this study was to quantify the prognostic
      significance of HR from the surface ECG obtained both at entry and at discharge,
      in a large population of patients all treated with fibrinolysis during the acute
      phase and having confirmed acute MI. METHODS AND RESULTS: Surface ECGs obtained
      at entry and at discharge in patients with confirmed MI enrolled in the GISSI-2
      study, a large multicentre trial of different thrombolytic agents, were
      retrieved. Heart rhythm was evaluated and HR was measured; these data were then
      added to the main database of GISSI-2 allowing a complete evaluation of the
      prognostic significance of HR. Patients not in sinus rhythm or with grade 2-3
      atrioventricular block were excluded. The prognostic significance of HR (cut-offs
      predefined at 60, 80, 100 beats.min-1) at entry for in-hospital mortality and at
      discharge for 6-month mortality was evaluated in the general population and in
      predefined subgroups. Multivariate analyses were used to assess the independent
      prognostic value of HR. A total of 8915 patients (more than 70% of the original
      population) were suitable for the analysis. There was a progressive increase in
      mortality with increasing HR in the general population (from 7.1% for HR < 60
      beats.min-1) to 23.4% for HR > 100 beats.min-1) and in the predefined subgroups.
      Multivariate analysis showed that HR exerted an independent prognostic
      significance. Data for analysis of HR at discharge were available for 7831
      patients. Consistent with the data observed at entry, a progressive increase of 6
      month mortality with increasing HR was present in the general population (from
      0.8% for HR < 60 beats.min-1) to 14.3% for HR > 100 beats.min-1) and for the
      different predefined subgroups. Multivariate analysis confirmed the independent
      prognostic significance of HR. There was no relation between HR and the incidence
      of fatal and non-fatal reinfarction. CONCLUSION: The present study indicates that
      HR values from a standard 12-lead ECG independently predict mortality in patients
      with acute MI during the in-hospital phase and after discharge. This simple index
      appears very useful for risk stratification in clinical practice.

PMID- 9651732
TI  - Effect of calcium antagonists on sympathetic activity.
AB  - OBJECTIVE: We evaluated the effects of calcium antagonists on sympathetic
      activity in hypertensive patients by searching Medline for English language
      articles published between 1975 and May 1996 using the terms calcium antagonists,
      sympathetic nervous system and catecholamines. METHODS: Data from clinical
      studies reporting only the effects of calcium antagonists on blood pressure,
      heart rate and plasma norepinephrine (NE) levels in patients with hypertension
      were analysed according to class of calcium antagonist (dihydropyridine vs non
      dihydropyridine), their duration of action (short-acting (SA) vs long-acting
      (LA)) and treatment duration. RESULTS: We identified 63 studies involving 1252
      patients. Acutely after single dosing, SA calcium antagonists decreased mean
      arterial pressure by 13.7 +/- 1.1% and increased heart rate by 13.7 +/- 1.4% and
      NE levels by 28.6% +/- 2.5%. Change in NE levels correlated with change in heart
      rate (r = 0.59, P < 0.01) and inversely with change in arterial pressure (r =
      0.46, P < 0.05) in patients taking dihydropyridine calcium antagonists acutely.
      With sustained therapy, both classes of SA calcium antagonists increased NE
      levels. Whereas NE levels remained slightly elevated and heart rate unchanged
      with LA dihydropyridine calcium antagonists, both heart rate and NE levels
      decreased with LA non-dihydropyridine calcium antagonists. SA calcium antagonists
      stimulate sympathetic activity when given acutely and over the long term,
      irrespective of their molecular structure. In contrast, sympathetic activation is
      less pronounced with LA dihydropyridine calcium antagonists and falls with LA non
      dihydropyridine calcium antagonists. CONCLUSIONS: The present findings offer a
      possible pathophysiological explanation for the increase in morbidity and
      mortablity observed in some studies using SA calcium antagonists.

PMID- 9651733
TI  - Role of sympathetic nervous system in hypertension and effects of cardiovascular
      drugs.
AB  - The sympathetic nervous system (SNS) plays an important role in the regulation of
      cardiac performance and peripheral circulation. Changes in SNS activity measured
      as catecholamines in plasma or organ spillover have been implicated in the
      pathogenesis of hypertension. Recent studies using microneurography to directly
      assess peripheral sympathetic nerve activity have demonstrated an increase in
      sympathetic activity in patients with borderline hypertension at rest and during
      hypoxia. We have recently shown that resting muscle sympathetic nerve activity is
      comparable in offspring of hypertensive and normotensive parents. However, during
      mental arithmetic the increase in muscle sympathetic nerve activity and blood
      pressure was significantly more pronounced in offspring of hypertensive than in
      offspring of normotensive parents, but resting blood pressure was in the
      normotensive range and comparable in both groups. These data indicate that the
      response to mental stress results in a more pronounced activation of SNS in
      normotensive subjects with a genetic background of hypertension. In other
      cardiovascular disease states such as acute myocardial infarction and heart
      failure activity of the SNS may determine prognosis significantly. Some calcium
      antagonists which are successfully used to treat patients with hypertension and
      stable angina pectoris may have unfavourable effects in patients with impaired
      left ventricular function. This could be due in part to baroreceptor-mediated
      activation of the SNS, an effect which seems to be related to pharmacokinetics
      and pharmacodynamics of the drugs. In contrast, angiotensin converting enzyme
      inhibitors seem to directly decrease sympathetic nerve activity. This may explain
      at least in part their beneficial effects in patients with impaired left
      ventricular function. Thus, the SNS as a regulator of the cardiovascular system
      also plays an important role in the pathophysiology of cardiovascular diseases
      such as hypertension, myocardial infarction and heart failure. Furthermore, drug
      therapy could have a significant impact on the activity of the SNS.

PMID- 9651734
TI  - The sympathetic nervous system in hypertension: differing effects of drug
      treatment.

PMID- 9651735
TI  - The neuroendocrine and sympathetic nervous system in congestive heart failure.
AB  - A review of recent randomized clinical trials has shown that neurohormonal
      activation starts early in the natural history of left ventricular dysfunction
      and levels of the circulating hormones increase in proportion to the severity of
      heart failure. Most studies suggest that high levels of neurohormones predict a
      poor prognosis. Among the several neurohormones, the sympathetic system is the
      one which is activated earlier, it increases in proportion to the severity of the
      disease and has a negative prognostic implication. These concepts have been also
      proven in untreated patients. Augmented sympathetic activity in the syndrome of
      heart failure is initially beneficial, appears to be adaptive and helps support
      blood pressure and cardiac output. Prolonged and excessive sympathetic activation
      has deleterious effects with adverse consequences at both cardiac and vascular
      levels which aggravates the clinical status of the syndrome and negatively
      affects its prognosis. Evidence is accumulating that, contrary to popular belief,
      beta-blockers may be beneficial in heart failure by inhibiting sympathetic
      activation. In addition to neuroendocrine activation, another class of
      biologically active molecules, termed cytokines, are excessively secreted by
      cells in heart failure. Important among these cytokines are tumour necrosis
      factor-alpha and interleukin-6. They appear to exert deleterious effects on the
      heart and circulation which may be also involved in the progression of heart
      failure.

PMID- 9651736
TI  - Beta-blockers in heart failure.
AB  - Beta-blocker therapy for heart failure has gained popularity as a result of
      recent growing evidence that this group of drugs can reverse or slow the
      progressive left ventricular dilation that characterizes heart failure. Although
      the mechanism of this favourable effect on remodelling remains unclear, the
      present evidence indicates that at least a portion of the long-term benefit of
      these drugs is mediated through their beta-blocking action. A direct effect on
      myocyte and interstitial growth may be a key factor in their ability to inhibit
      the remodelling process. The growing database will eventually raise the
      possibility that all patients with left ventricular dilation should take one of
      these drugs. A better understanding of differing mechanisms in individual
      patients would ideally provide selectivity in the therapeutic approach.

PMID- 9651737
TI  - Catecholamine levels and treatment in chronic heart failure.
AB  - Neurohormonal activation is well studied in chronic heart failure, and covers
      aspects such as abnormalities of plasma catecholamines, particularly since plasma
      noradrenaline levels have been found to predict impaired prognosis in heart
      failure patients. This review will concentrate on the information available on
      circulating levels of adrenaline and noradrenaline. It will discuss how
      catecholamine levels change during different disease stages from myocardial
      infarction to severe chronic heart failure. It has been clearly shown that
      angiotensin converting enzyme (ACE) inhibitors exert particularly beneficial
      effects in heart failure patients with raised catecholamine levels. Nevertheless,
      reviewing how a variety of drug and non-drug interventions affect catecholamine
      levels and patients' survival, it is concluded that the effect on catecholamine
      levels does not directly correlate with a survival benefit of the respective
      intervention. Despite their prognostic significance, due to the development of
      new prognostic markers for patients with chronic heart failure, the overall
      clinical value of spot catecholamine levels remains limited.

PMID- 9651738
TI  - The sympathetic nervous system and ischaemic heart disease.
AB  - The sympathetic nervous system, coronary artery disease and myocardial ischaemia
      are related in different ways. First, the sympathetic system may be involved in
      the process of atherosclerosis through platelet activation and subsequent
      platelet-derived growth factor formation and by inducing mechanical injury to the
      vascular wall as a result of increased blood pressure and increased flow
      velocity. Secondly, sympathetic control of coronary vasomotor tone, which under
      normal conditions is not important, becomes functionally significant once
      coronary artery disease endothelial dysfunction has occurred. Under these
      circumstances, increased sympathetic adrenergic tone may lead to coronary
      vasoconstriction and, as myocardial oxygen demand increases concomitantly,
      myocardial ischaemia may ensue. Alternatively, myocardial ischaemia activates
      several neurohormonal systems, such as the sympathetic and, during more severe
      ischaemia, the circulating renin-angiotensin system. This leads to systemic and,
      possibly, coronary vasoconstriction and thus to further myocardial ischaemia.
      Prolonged myocardial ischaemia results in progressive norepinephrine release from
      the heart, reaching extracellular levels as high as 100-1000 x plasma
      concentrations. As cardiac beta-receptor density rises simultaneously,
      sympathetically-induced irreversible myocardial damage may occur, although
      through concomitantly increased beta-receptor kinase activity the beta-receptor
      may become functionally inactive. To counteract the detrimental effects of
      enhanced sympathetic activation on the heart, beta-blockade appears to be the
      proper choice. However, acute beta-blockade may lead to more profound ischaemia
      induced neurohormonal activation and hence to vascular constriction through
      unoccupied alpha-receptors. In contrast, under ischaemic conditions and with
      concomitant beta-blockade, acute alpha-blockade does improve subendocardial flow
      and reduces myocardial ischaemia. A novel approach to anti-ischaemic therapy,
      which relates to modulating ischaemia-induced sympathetic activation, is through
      ACE inhibition. ACE inhibitors affect myocardial ischaemia by reducing
      neurohormonal activation and related systemic and coronary vasoconstriction.
      These acute effects may become more important over time, as coronary endothelial
      function improves following long-term ACE inhibition. A large multicentre
      controlled trial comparing ACE inhibition with placebo in patients with coronary
      artery disease, the EUROPA (EUopean trial on Reduction Of cardiac events with
      Perindopril in stable coronary Artery disease), which is currently underway,
      addresses the issue of whether ACE inhibition does in fact offer a novel approach
      in myocardial ischaemia.

PMID- 9651740
TI  - Blastoderm structure, cell migration and formation of the embryonic shield during
      gastrulation in the carp (Cyprinus Carpio); a scanning electron microscopic
      study.
AB  - This paper describes an ultrastructural study of the cell movements during the
      gastrulation of the common carp, Cyprinus carpio, using scanning electron
      microscopy. The morphology of the deep cells was studied in several consecutive
      stages ranging from 0-100% epiboly. Furthermore, the formation of the embryonic
      shield was followed from its earliest appearance at 50% epiboly onwards. This
      paper gives morphological evidence for the existence of two different pathways
      for involving and convergent movements. Firstly, cells may move along the inner
      surface of the not (yet) involuted cells. Secondly, a much smaller group may use
      the YSL as their substrate. These results are discussed in the light of the
      hypothesis that the two migrating cell populations may be differently induced,
      subsequently leading to the formation of mesoderm and endoderm.

PMID- 9651739
TI  - The autonomic nervous system and sudden death.
AB  - The knowledge progressively accumulated on the relation between changes in
      autonomic activity and cardiac mortality, particularly in the setting of acute
      myocardial ischaemia, has turned during the last decade toward the potential
      prognostic value of markers of autonomic activity. Two of these markers, heart
      rate variability and baroreflex sensitivity, have gained progressive popularity.
      This chapter reviews some of the experimental observations that were instrumental
      for the novel clinical approach to post-myocardial infarction risk stratification
      based on the use of autonomic markers as risk stratifiers. It then focuses on
      clinical studies with special attention for a very recent multicentre prospective
      study (ATRAMI) carried out in almost 1300 post-myocardial infarction patients and
      aimed at the evaluation of the prognostic value of both heart rate variability
      and baroreflex sensitivity. Finally, some pathophysiological considerations are
      added to clarify the legitimacy, or lack of it, of the terminology currently used
      in clinical studies based on autonomic markers.

PMID- 9651741
TI  - Ultrastructure of rat atrial tissue after either perfusion-or immersion-fixation
      both in vivo and in vitro study: comparison of methodological reliability.
AB  - The present study compares, from a morphological point of view, the possible
      differences between perfusion- and immersion-fixation techniques performed on rat
      myocardium in order to evaluate their reliability. The data we obtained showed
      that when the two techniques are carried out with particular care, they do not
      present significant differences in tissue preservation. Furthermore, we also
      evaluated the ultrastructural of rat myocardium at the end of in vitro
      experiments. In this case, signs of subcellular changes, such as vacuolar
      degeneration, swollen mitochondria, intermyofibrillar myelin-like figures and
      enlargements of non specialized junctions of the intercalated discs can
      frequently occur. So, our results indicate that the morphological integrity of
      myocardium is not completely preserved during in vitro investigations.

PMID- 9651742
TI  - Sublethal alterations and sustained cell proliferation associated with the
      diethylstilbestrol-induced renal carcinogenesis in male Syrian golden hamsters.
AB  - The current study was initiated to explore the sublethal alterations and the
      tissue damage occurring in the hamster kidney during diethylstilbestrol-induced
      renal carcinogenesis. A total of 49 male Syrian golden hamsters (35 treated and
      13 control animals) was utilized in the experimental procedure. Chronic exposure
      to diethylstilbestrol was achieved by s.c. insertion of implants containing 25 mg
      diethylstilbestrol. For long-term observation, adequate blood level of
      diethylstilbestrol was insured by renewing the implant every 2 months.
      Experimental groups (n = 4 to 9) were terminated 1, 2, 4, 6, 9 and 11 months
      after initial implantation for morphological examination of the kidney.
      Diethylstilbestrol carcinogenicity in this experimental model was confirmed by
      the observation that most animals undergoing drug exposure for 6 months or more
      exhibited renal neoplasms. The most striking nonneoplastic morphological
      abnormality disclosed by histological and cytological examination consisted in
      the accumulation of granular inclusions in proximal tubule cells. In renal
      tissue, the extent of cell proliferation determined by PCNA labeling
      progressively increased along with the duration of diethylstilbestrol exposure
      and suggested a sustained proliferative response in altered proximal tubules. The
      present data suggest that an impairment of functional tubular regeneration could
      promote, as well as the estrogen genotoxic effect, the tumorigenicity of
      diethylstilbestrol in the kidney of male hamsters.

PMID- 9651743
TI  - Light and scanning electron microscopic study of the palatine mucosa of nine
      banded armadillo (Dasypus novemcinctus).
AB  - The three-dimensional structure of the lamina propria of the hard and soft
      palatine mucosa of the nine-banded armadillo was observed by scanning electron
      microscopy. Sodium hydroxide cell maceration method was applied to demonstrate
      the architecture of the connective tissue papillae. The palatine mucosa of the
      armadillo had a triangular shape and measured appr. 6.5 cm length. The hard
      palate showed 9 transverse palatine plicae while the soft palate was smooth. In
      the 10% NaOH treated specimens, the lamina propria of the hard palatine mucosa
      showed numerous connective tissue papillae with a general finger-like shape.
      These structures were composed by a meshwork of collagen fibers arranged in
      several directions. On the other hand, the connective tissue papillae of the soft
      palate mucosa were scattered and small. Numerous openings of glandular ducts with
      circular or elliptical shape were located in the interplicae area and in the soft
      palate.

PMID- 9651744
TI  - A quantitative study of the ventricular myoarchitecture in the stage 21-29 chick
      embryo following decreased loading.
AB  - During the early developmental period, ventricular myoarchitecture undergoes a
      transition from a smooth-walled cardiac tube, to left and right ventricular
      chambers filled with a sponge-like network of trabecular struts. We measured the
      quantitative changes of ventricular myocardium properties in normal stage 21-29
      chick embryos and after chronic verapamil suffusion, which is known to decrease
      work load and decelerate ventricular growth. The morphologic parameters (compact
      layer thickness, ventricular wall composition, porosity of different layers and
      trabecular orientation) were determined from scanning electron micrographs of
      transversely dissected perfusion-fixed hearts. A vascular bed of stage 21 chick
      embryos was suffused with 1 ng of verapamil at 1 microliter per hour up to stages
      24, 27 and 29 via a miniosmotic pump. From stage 24, the thickness of the compact
      myocardium in the left ventricle was greater than that of the right. The increase
      in thickness was minimal between stages 24 and 27, while the predominantly
      radially arranged trabeculae comprised up to 75% to total myocardial mass. The
      ratio of intertrabecular spaces to trabeculae (local porosity) decreased form the
      ventricular center (70%) towards the compact myocardium (0%). In verapamil
      treated embryos, the hearts were smaller and showed delayed development. The
      compact myocardium was thinner than normal, and the proportion of trabeculae was
      higher than in controls. The local porosity values were similar in control and
      experimental groups. Decreased load resulted in delayed growth and morphogenesis,
      expressed as persistence of trabeculae and a thinner compact myocardium.
      Embryonic heart pumping function is largely based on extensively developed
      trabeculation with regionally different properties.

PMID- 9651746
TI  - EUROSON 98--SFAUMB 98. 10th Congress of EFSUMB--19th Congress of SFAUMB. March 26
      30, 1998, Tours, France. Abstracts.

PMID- 9651745
TI  - Sensory innervation of myosin heavy chain-based types of chicken intrafusal
      fiber.
AB  - Chicken intrafusal fibers that had been categorized as slow or fast contracting
      by their reactions with monoclonal antibodies against myosin heavy chains (MHC)
      at polar regions were examined at the equator and neighboring juxtaequator to
      determine if fiber type-specific morphologies were also present at the sensory
      region. The parameters chosen for examination were contractile filaments,
      distribution of acetylcholinesterase and sensory innervation. Evaluation of
      acetylcholinesterase was included to define the proximal limit of motor terminal
      distribution. At the equator actin was primarily restricted to a thin layer
      beneath myosensory junctions. Myosin heavy chains at the equator and the
      juxtaequator were more evenly distributed. Although absent from the synaptic side
      of the sensory region, acetylcholinesterase activity was present on the
      extrasynaptic side. Plots of diameters of sensory axon collaterals and of sensory
      endings yielded continuous spectra instead of distinct peaks. Taken together,
      these features indicated a uniform equatorial morphology. However, sensory
      terminals to fast intrafusal fibers were longer and narrower than those to slow
      intrafusal fibers, and typically more terminals impinged on fast than on slow
      intrafusal fibers. Moreover, in the larger spindles short sensory terminals were
      most prevalent near the equatorial-juxtaequatorial junction, the region where in
      mammalian intrafusal fibers secondary sensory axons make contact. The differences
      seen in sizes and distributions of terminals suggest that, despite the lack of
      type-specific morphologies at the sensory region of chicken intrafusal fiber
      types, some level of functional separation is maintained there.

PMID- 9651747
TI  - Deconstructing the dialectic.
AB  - The author examines some of the newly offered ideas and concepts about the
      interaction of the patient and the analyst. This interaction is termed a
      dialectic in the sense of interacting forces and this study is called a
      deconstruction, which is an effort to see how unstable and self-contradictory
      these new ideas may be. They are examined in terms of viewpoints of analysis as a
      developmental process, the location of the data of analysis, and the technical
      modifications that follow from this changed theoretical vision. A clinical
      example is offered to demonstrate the resultant problems. The suggested present
      status of the impact of these new ideas is that of a family of related concepts
      with no unifying theory.

PMID- 9651748
TI  - The changing aims of psychoanalytic psychotherapy. An integrative perspective.
AB  - The purpose of this paper is to relate traditional psychoanalytic ideas on aims
      and outcomes to the changing world of contemporary psychoanalytic psychotherapy,
      with its financial constraints and theoretical and technical innovations. An
      emphasis on splitting rather than repression, on the nature of the attachment
      between therapist and patient, and on realistic goals and modest change all
      characterise contemporary perspectives. Recent developments in the cognitive
      behavioural psychotherapy literature indicate possible areas of overlap with
      psychoanalytic psychotherapy. Attachment theory proposes that patient-therapist
      attunement is likely to be a key variable in outcome. Since attunement is
      intrinsically responsive rather than directive, the paradox of psychoanalytic
      'aimlessness' is inherent in the nature of psychoanalytic psychotherapy.

PMID- 9651749
TI  - From simplicity through contradiction to paradox. The evolving psychic reality of
      the borderline patient in treatment.
AB  - The thesis of this paper is two-fold. First, it proposes that the psychic reality
      of the borderline patient evolves in a three-step process during the analytic
      treatment. These steps include: (i) experiencing and presenting disparate psychic
      states without the awareness of inherent contradictions, (ii) observing,
      acknowledging, and mending the splits responsible for these contradictions, and
      (iii) developing a capacity for feeling and accepting paradox, i.e. coexistence
      of multiple meanings at different levels of abstraction. Second, the author
      suggests that this three-step movement vis-a-vis the associative material takes
      place first within the analyst's reverie and then in the patient's psychic
      reality. The analyst's holding, unmasking, bridging and depth-rendering
      interventions (and the vicissitudes of identification) make the patient's advance
      possible. The author presents two clinical vignettes, highlighting these
      hypotheses and their technical implications. A vignette from the non-clinical
      realm of a mother's interaction with her children is also included in the hope of
      demonstrating a developmental 'Anlage' of the analyst's interventions outlined
      above. The paper concludes with the observation that the practising analyst also
      needs to traverse a 'simplicity-contradiction-paradox' sequence in his view of
      the divergent theoretical approaches to the analytic understanding and treatment
      of severe character pathology.

PMID- 9651750
TI  - The poignant, the excessive and the enigmatic in sexuality.
AB  - The author offers a contribution to redressing a certain lack of theorization
      concerning the specific power and meaning of sexuality. This begins with George
      Klein's suggestion that it is the quality of a specific, poignant sensuality that
      characterizes sexuality. Bataille's ideas about the violent and excessive aspects
      of eroticism provide some answers to the question of what makes for this special
      poignant quality. Bataille captures a profound link between the sacred and the
      erotic with regard to their both being linked with taboos and their transgression
      as opposed to habitual 'work mentality' and established order. The excessive
      dimension highlighted by Bataille is complemented in the work of Laplanche about
      sexuality as opposed to 'functional', self-preservative ego needs, and the excess
      of the 'enigmatic message' transmitted by the mother while satisfying the
      infant's ego needs that establishes the infant's unconscious and sexuality.
      Losing the nutritive object, a process of fantasizing sets in; the influx of
      strong sensations that cannot yet be integrated spills over into libidinal
      excitement. The gap between the other's excess and the child's limited resources
      can then be sexualized. A picture emerges of non-procreative sexuality as foreign
      to ordinary experience and as transcending one's limits.

PMID- 9651751
TI  - A look at the Salome-Freud correspondence.
AB  - The author notes that the changing emphasis of the correspondence between Lou
      Andreas-Salome and Sigmund Freud over the years reflects certain aspects of the
      development of every analyst. Her contributions are shown to illustrate the
      evolution of the analyst's relationship with theory and the growth of his or her
      clinical capacity and involvement. Two phases in the analyst's clinical
      progression are stated to be discernible in the correspondence, marked by changes
      of direction that mirror the changing nature of her relationship with Freud.
      Theoretical considerations predominate in the first phase, while clinical aspects
      gradually come to the fore in the second. Freud is seen to be offering Salome a
      kind of supervision by letter. Lou's underlying transference to Freud also
      emerges from the correspondence, its two aspects being the relationship to a big
      brother and to a father respectively. Freud's complementary transference to
      Salome is also discussed, partly in connection with her relationship with his
      daughter Anna. The author's arguments are supported by extensive quotations from
      the correspondence, biographical works and Lou Andreas-Salome's published diaries
      and reminiscences. Last but not least, her relationship with Freud in the
      author's view indirectly raises the issue of that of any analyst to the founder
      of psychoanalysis.

PMID- 9651752
TI  - The Ambulatorium: Freud's free clinic in Vienna.
AB  - At the close of World War I, Freud proposed the creation of clinics providing
      free treatment, in the first of a series of politically liberal statements
      promoting the development of a kind of institution that is rarely associated with
      psychoanalysis today. Using archival and oral history research methods, this
      study offers a descriptive and statistical history of the Vienna Ambulatorium,
      the free psychoanalytic clinic and child guidance centre created--we can now
      surmise--under Freud's direction. Presented within the cultural context of
      central Europe's inter-war rush of progressivism in 'Red Vienna' and in Germany's
      Weimar Republic, little-known aspects of the history of psychoanalysis emerge.
      From 1922 to 1936, the staff of the Ambulatorium treated gratis patients of all
      ages and social classes, ranging from professional to unemployed. Candidates too
      were analysed at no cost. Reflecting the urban energy of his era, Freud believed
      that psychoanalysis could be both productive and free of cost. What emerges is an
      unexpectedly activist, community-oriented profile of some of the earliest
      participants in the psychoanalytic movement.

PMID- 9651753
TI  - Never before and never again. The compulsion to repeat, the fear of breakdown and
      the defensive organisation.
AB  - In this clinical communication, the author discusses the compulsion to repeat
      past trauma within the area of personal omnipotence provided in the transference,
      the fear of breakdown that may arise in the course of an analysis, and the
      defensive organisation deployed by the patient in the interest of survival. The
      development of and some connections between the compulsion to repeat, the fear of
      breakdown and the defensive organisation are illustrated and discussed in light
      of the writings of Freud, Winnicott and various Kleinian authors and some of the
      factors that may contribute to the emergence of the fear of breakdown--those
      inherent in both the analytic setting and in the early history and character of
      the patient--are exemplified by the case of one analysand which is offered to
      highlight further the dynamics of a particular variety of defensive organisation
      against breakdown.

PMID- 9651754
TI  - Chronicle of an incest foretold.
AB  - In this paper the author discusses the situation of children handed over to
      grandparents or to other relatives of the natural parents to be brought up. She
      notes that such children are faced with the riddle of their own filiation and
      postulates that this scenario often conceals an oedipal fantasy to the effect
      that the child concerned is the fruit of an incestuous relationship between a
      grandparent and the relevant parent. Following the example of Freud, the author
      adduces literary models for illustration. As with the Oedipus of Sophocles, the
      author shows how efforts to thwart the workings of fate actually bring about the
      consummation of the tragedy in the form of incest, which is favoured by the
      confused oedipal configuration in the families of handed-over children. The main
      argument is based on the characters and situations of two novels by Gabriel
      Garcia Marquez, written at different times in his life. With reference to the
      psychoanalytic literature on artistic creativity, the author shows the importance
      of the mid-life crisis in determining how Garcia Marquez came to terms with the
      fact of having himself been entrusted to grandparents as a child and how this
      situation is reflected in the works concerned.

PMID- 9651755
TI  - Illusion and uncertainty in psychoanalytic writing.
AB  - Psychoanalytic writing may be viewed as a particular version of creative process.
      As such, it evokes many of the self and object-related anxieties and conflicts
      associated with creative expression. This paper considers the role of illusion in
      facilitating an entry into the psychoanalytic writing process in the light of
      contemporary relational and feminist perspectives. It is suggested that the
      writer who struggles to write may engage certain real or internalized object
      experiences to retreat to a transitional idealized self-state and to enter the
      writing process. Two variants of this subjective state are described, based on
      Winnicott's notion of 'being' and 'doing' as underlying dimensions of human
      experience. Each self-state excludes a particular set of self- and object-related
      anxieties and creates a temporary illusion of creative certainty. That illusion
      helps the writer temporarily to avoid self-doubt and anxiety in order to enter
      the creative arena Ultimately, however, the protected writing space must expand
      if the writer is to address and integrate the world of psychoanalytic ideas
      within the writer's own creative process. This process is illustrated by a
      description of the evolution of my own experience as a psychoanalytic writer.

PMID- 9651756
TI  - Emotional processing: the mind-body connection.

PMID- 9651757
TI  - Presentation of clinical material on sexuality.

PMID- 9651758
TI  - Sexuality in the analysis of adolescents: its impact on the transference
      countertransference.

PMID- 9651759
TI  - Presentation of clinical material on sexuality.

PMID- 9651760
TI  - Mass sexuality/private sexuality.

PMID- 9651761
TI  - The Holocaust.

PMID- 9651762
TI  - Castration as an organiser of bisexuality.

PMID- 9651764
TI  - Film reviews guest editorial.

PMID- 9651763
TI  - Psychosis.

PMID- 9651765
TI  - Robert Caper on 'A mind of one's own' (IJPA, 78: 265-278)

PMID- 9651766
TI  - Hitchcock's Vertigo: the collapse of a rescue fantasy, by Emanuel Berman (Int. J.
      Psychoanal., 78: 975-996)

PMID- 9651767
TI  - Historicising the origins of Kleinian psychoanalysis (IJPA, 78: 1165-1182)

PMID- 9651768
TI  - 'The elusive concept of "Internal Objects" (1934-1943)' by R. D. Hinshelwood.

PMID- 9651769
TI  - Defatted, gas-sterilised cortical bone allograft for posterior lumbar interbody
      vertebral fusion.
AB  - In posterior lumbar interbody vertebral fusion operations, variously sized,
      rectangular shaped, defatted, freeze-dried, gas-sterilised cortical bone
      allografts were used in combination with cancellous bone autografts from excised
      posterior elements. Single-level fusion, with or without internal fixation, was
      undertaken in 38 patients aged 50 years or less with disc herniation or a failed
      discectomy (the younger group) and in 33 women aged 60 years or more with
      degenerative spondylolisthesis (the older group). Of the various observable
      indicators of union, changes in the allograft-host interface alone proved to be
      of practical use. The incidence of nonunion in patients managed with pedicle
      screws, with a hook and rod system or without internal fixation was 0 of 8
      patients; 1 of 14 patients; and 3 of 16 patients, respectively, in the younger
      group, and 0 of 11 patients; 0 of 8 patients; and 2 of 14 patients, respectively,
      in the older group. Of the six patients with nonunion, three had persistent low
      back pain and only two had mobility of the fused segment which was evident on
      lateral radiographs during flexion and extension. No patient had graft collapse.
      The decrease in the height of the intervertebral space, chiefly due to settlement
      of the allograft into the vertebral bodies, in the younger and older groups
      averaged 1.1 and 1.6 mm, respectively. We concluded that this simplified
      technique is mechanically sound and effective in maintaining the height of the
      intervertebral space. Even when the graft failed to unite, fibrous union could be
      obtained without graft collapse. Combination with a simple internal fixator, such
      as a compression rod, facilitates bone union.

PMID- 9651770
TI  - Anterior lumbar vertebral translation following translaminar screw fixation. A
      report of five cases.
AB  - Translaminar screw fixation is a good procedure for posterolateral spinal fusion
      of one or two motion segments. Anterior translation of the upper fused vertebra
      occurred in 5 of our patients following this procedure. A further fusion with
      pedicle screw fixation was needed in 2 of them. This complication has been
      previously reported after decompression operations on the lumbar spine.
      Translaminar screwing produces slight posterior distraction which pushes forward
      the upper vertebra. This procedure should be avoided in cases with even minimal
      anterior translation before operation. Translaminar screw fixation is an ideal
      technique for fusion of a degenerated segment when the upper vertebra has slipped
      posteriorly.

PMID- 9651771
TI  - Infantile idiopathic scoliosis in the newborn.
AB  - We have reviewed 7 patients (5 boys and 2 girls) with infantile idiopathic
      scoliosis which was present at birth and was diagnosed at ages from 1 day to 1
      month. The mean follow up was 16 years. The objectives were to discover whether
      intrauterine forces play a role in the aetiology and to determine whether early
      treatment of a potentially progressive curve can induce resolution. Two infants
      were male conjoined twins and were united by skin over the posterior sacrum. Six
      infants had a rib vertebral angle difference greater than 20 degrees in the first
      radiograph and 5 had stiff curves. In 2 with flexible curves, the deformity
      disappeared by the end of the first year. The 5 with stiff curves were treated
      conservatively for 6 to 24 months. Growth has now been completed in 5; 4 have a
      straight spine and one developed an adolescent curve of 26 degrees. The 2 who are
      still growing have no scoliosis. Intrauterine moulding was only demonstrated in
      the conjoined twins. There was a correlation between the rib vertebral angle
      difference above 20 degrees and the rigidity of the curve. Early treatment of a
      potentially progressive curve can lead to resolution.

PMID- 9651772
TI  - Osteotomy at the knee for advanced cases of Kashin-Beck disease.
AB  - The results of 247 osteotomies at the knee were analysed in 195 patients with
      Kashin-Beck disease. Since 1983, 37 varus and 210 valgus deformities have been
      operated on. Supracondylar osteotomy was carried out so that there is a cortical
      spike in the distal metaphysis which is impacted into the femoral condyle. A U
      shaped tibial osteotomy is made 0.5 cm below the growth plate and around the
      insertion of the patellar ligament. The mechanical axis is corrected and
      stability obtained by impacting the fragments; internal fixation is not used.
      Correction of the initial angular deformities was achieved after the osteotomies,
      and function was improved.

PMID- 9651773
TI  - Patellofemoral contact forces and pressures during intramedullary tibial nailing.
AB  - Patellofemoral joint forces and pressures were measured in a cadaver model during
      intramedullary nailing of the tibia. A significant increase in contact pressures
      was found at the lateral facet of the patellofemoral articulation using the
      medial paratendinous approach (P = 0.01) and at the medial facet when using the
      trans-patellar tendon approach (P = 0.001) to the proximal tibia. Increased
      contact pressures at the patello-femoral joint may result in chondral injury,
      which in turn may cause anterior knee pain, a common complication of tibial
      nailing.

PMID- 9651774
TI  - Unreamed intramedullary locking nailing for open tibial fractures.
AB  - We reviewed the results of the treatment of 24 cases of open tibial fractures
      using unreamed intramedullary locking nailing. The fractures were classified,
      following the Gustilo system as grade I-7, grade II-7 and grade III-10. The
      average time to achieve bony union was 22 weeks with a 26% incidence of
      pseudoarthrosis. There were no cases of deep infection. Five cases healed with
      shortening of over 1 cm, but we did not observe angular deformity in any of the
      patients. In 2 fractures with associated articular lesions, joint motion was
      limited at final follow up. The nail broke in 2 cases and the screws in 5. The
      surgical procedure is well tolerated by patients, allows good management of soft
      tissue lesions and rehabilitation with low rate of infection and malunion. The
      main disadvantages have been the relative high incidence of nonunion and breakage
      of metal.

PMID- 9651775
TI  - The posterior interosseous nerve and the radial tunnel syndrome: an anatomical
      study.
AB  - Twenty anatomical specimens were carefully studied in order to establish a
      possible connection between the posterior interosseous nerve and the radial
      tunnel syndrome. Our results show that the posterior interosseous nerve distal to
      the supinator muscle may be compressed by various structures. These include the
      distal border of the supinator muscle, the ramifications of the anterior and
      posterior interosseous vessels, and the septum between the extensor carpi ulnaris
      and the extensor digitorum minimi. The posterior interosseous nerve is also
      stressed during passive supination (elongation and rotation), and during passive
      pronation (compression). This suggests that the interosseous nerve distal to the
      supinator muscle should be explored in radial tunnel compression syndromes.

PMID- 9651776
TI  - The value of an operating microscope in peripheral nerve repair. An experimental
      study using a rat model of tibial nerve grafting.
AB  - The aim of this study was to test the hypothesis that the use of an operating
      microscope improves the results of peripheral nerve repair. Tibial nerve grafting
      was carried out on 48 Fischer rats divided into 2 groups: in one, a loupe was
      used, and in the other a surgical microscope. At 5 months after grafting,
      recovery was evaluated by functional, electromyographic, and morphometric tests.
      The mean motor nerve conduction velocity was 26.77 +/- 9.37 m/sec in the group
      where the loupe was used compared with 44.19 +/- 11.36 m/s when the microscope
      group was used. The soleus muscle weight and the diameter of myelinated fibres
      also confirmed better regeneration in the microscope group. These results clearly
      indicate that it is essential to use the microscope for peripheral nerve repair.

PMID- 9651777
TI  - Evaluation of simplified Frykman and AO classifications of fractures of the
      distal radius. Assessment of interobserver and intraobserver agreement.
AB  - In order to evaluate interobserver and intraobserver agreement of the Frykman and
      AO classifications and their variations between assessors with different levels
      of experience, three hand specialists, a fellow and two senior residents
      classified radiographs of 200 fractures of the distal radius in anteroposterior
      and lateral views. Reproducibility was assessed by the use of the proportion of
      agreement and kappa coefficient between pairs of observers. The Frykman
      classification showed moderate interobserver reproducibility (kappa = 0.43) and
      good intraobserver reproducibility (kappa = 0.61). The experience of the
      reviewers did not significantly affect either of these. The AO system showed
      regular interobserver reproducibility (kappa = 0.37) and moderate intraobserver
      reproducibility (kappa = 0.57). The younger group obtained higher intraobserver
      agreement than the senior. Possible causes for the low reproducibility of both
      classifications are discussed together with a review of the literature. We do not
      recommend the Frykman or AO classifications for clinical application because of
      their questionable reproducibility.

PMID- 9651778
TI  - Simulation by stereographic processing of computed tomography for
      transtrochanteric rotation osteotomy in necrosis of the femoral head.
AB  - The transtrochanteric rotation osteotomy described by Sugioka will preserve the
      femoral head in patients with avascular necrosis of the femoral head, but there
      is controversy about the clinical results. We developed a simulation system for
      rotation osteotomy, based on stereographic processing through computed
      tomography, the object being to determine the indication for this procedure and
      the degree of rotation required. This method makes it possible to determine the
      degree of rotation needed to displace the necrotic areas from the weightbearing
      zone; the need for a varus osteotomy can also be assessed. Our clinical results
      improved when we used this method. CT stereographic drawings in patients with
      avascular necrosis of the femoral head are useful for assessing the necrotic
      area.

PMID- 9651779
TI  - Rotationplasty as a limb salvage procedure for malignant bone tumours.
AB  - Sixteen patients with malignant bone tumours, 15 osteosarcoma and one Ewing's
      sarcoma, were treated by rotationplasty at Tata Memorial Hospital between 1989
      and 1994. The functional results are better than after amputation.

PMID- 9651780
TI  - External fixation in tumour pathology.
AB  - An appraisal of the clinical records of patients with malignant bone tumours
      enabled us to identify 61 whom we have treated by external fixation. There were
      38 males and 23 females with ages ranging from 4 to 58 years, the mean being 14
      years. The average period of follow-up was 6 years (1-12 years). For the purpose
      of our analysis the patients were divided into three groups according to whether
      the fixator was fitted before, during or after tumour resection.

PMID- 9651781
TI  - Skeletal metastases of intermediate grade chondrosarcoma without pulmonary
      involvement. A case report.
AB  - Although pulmonary metastases are typical of chondrosarcoma, only 2 patients with
      intermediate grade tumours have been reported with bone metastases and without
      pulmonary involvement. We report one patient with an intermediate grade
      chondrosarcoma which metastasised to the lumbar spine following surgical
      resection of a locally recurrent tumour. The local recurrence and the metastases
      were resected and she is alive and well after 20 months.

PMID- 9651782
TI  - Simple bone cysts treated with aspiration and a single bone marrow injection. A
      preliminary report.
AB  - The results of a single percutaneous aspiration and injection of marrow into
      active, simple bone cysts are reported in 8 cases. Slow regression of the cyst
      was consistently observed except in one lesion in the distal tibia. All the
      patients have been free of symptoms after this treatment after a mean follow up
      of 31 months. The evolution of the cysts was monitored by a cyst index, cyst
      diameter measurements and computer assisted densitometric image analysis of
      serial radiographs.

PMID- 9651783
TI  - Congenital insensitivity to pain with anhidrosis. A case report.
AB  - We present a five-year-old girl with congenital insensitivity to pain with
      anhidrosis. A skeletal radiographic survey revealed several old fractures.
      Application of pilocarpine showed anhidrosis and nerve biopsy revealed a
      significant decrease in the number of myelinated and unmyelinated nerve fibres.

PMID- 9651784
TI  - Structural bases of Fc gamma R functions.
AB  - This review describes structures which determine the biological activities
      triggered by Fc gamma R and account for the cell-mediated functions of IgG
      antibodies in physiology and pathology. The binding specificity and affinity of
      Fc gamma R depend primarily on IgG-binding structures, in their immunoglobulin
      like extracellular domains. Binding is however also influenced by subunits that
      associate to multichain Fc gamma R. Effector and regulatory intracytoplasmic
      sequences that are unique to molecules of the Fc gamma RIIB family determine the
      internalization properties of these receptors. Immunoreceptor Tyrosine-based
      Activation Motifs (ITAMs) are intracytoplasmic effector sequences shared by Fc
      gamma R and other receptors involved in the recognition of antigen, which trigger
      cell activation and internalization. Immunoreceptor Tyrosine-based Inhibition
      Motifs (ITIMs) are intracytoplasmic sequences, shared by Fc gamma RIIB and a
      growing number of negative coreceptors which negatively regulate cell activation
      via ITAM-bearing receptors. Altogether, these structures enable IgG antibodies to
      exert a variety of finely tuned biological effects during the immune response.

PMID- 9651785
TI  - Human IgG Fc receptors.
AB  - Human IgG receptors constitute a family of glycoprotein complexes consisting of
      ligand-binding, and associated signaling chains. Three leukocyte classes (Fc
      gamma RI, II, and III) and one separate endothelial Fc gamma R class (FcRB) are
      defined which are expressed on hematopoietic and endothelial cells. Upon
      interaction with IgG, Fc gamma R initiate a plethora of signaling cascades
      involving receptor signaling motifs, and protein tyrosine kinases and
      phosphatases. These cascades ultimately culminate in activation or deactivation
      of effector cells, resulting in initiation or down-modulation of cellular
      processes. Recent evidence points to a crucial in vivo role of Fc gamma R in both
      initiation and regulation of inflammatory and cytotoxic responses. These Fc gamma
      R-mediated immune responses can be exploited to develop novel immunotherapies.

PMID- 9651786
TI  - IgG binding sites on human Fc gamma receptors.
AB  - The structure for the three human Fc gamma receptors classes Fc gamma RI (CD64),
      Fc gamma RII (CD32) and Fc gamma RIII (CD16) has been well characterized. Here
      the IgG binding sites on Fc gamma RII and Fc gamma RII with their responsive FG,
      BC and C'/E loops on the membrane proximal domains are described in detail. For
      Fc gamma RI the second extracellular domain is suggested as a key structure of
      IgG binding. The lower hinge regions of human and murine IgG binding to these Fc
      receptors and their structural relationship in Fc gamma R-IgG interactions are
      discussed. The potential of inhibiting the pathophysiological effects of Fc gamma
      receptors by blocking studies are considered for future therapeutic modalities.

PMID- 9651787
TI  - Soluble Fc gamma receptors: interaction with ligands and biological consequences.
AB  - Soluble Fc gamma receptors are produced by cleavage of the membrane receptors or
      by alternative splicing. They are found in biologic fluids. After a brief
      description of the structure and mode of production of soluble Fc gamma R, we
      address the question of ligands and function of the soluble Fc gamma R by using
      recombinant molecules and transgenic animals. We show that soluble Fc gamma R are
      not only IgG-binding factors which interfere with, and block, Fc-dependent immune
      reactions but also molecules that interact, in vitro, with non-Ig-ligands such as
      CR3 and CR4 and are trigger or regulate immune functions via these receptors.

PMID- 9651788
TI  - Structure and functions of CD23.
AB  - This review summarizes recent data on CD23, a low affinity receptor for IgE (Fc
      epsilon RII). CD23 is the only FcR which does not belong to the immunoglobulin
      gene superfamily. The CD23 molecule was discovered independently as an IgE
      receptor on human lymphoblastoid B cells [1], as a cell surface marker expressed
      on Epstein-Barr-Virus-transformed B cells (EBVCS) [2] and as a B-cell activation
      antigen (Blast 2) [3]. CD23 was shown to be a low affinity receptor for IgE
      [4,5]. Similar to most FcR, soluble forms of CD23 (sCD23) are released into
      extracellular fluids. The soluble fragments formed by proteolytic cleavage of
      surface CD23 are not only capable of binding IgE (IgE binding factors) but also
      exhibit multiple functions that are not IgE related. These observations together
      with the finding that CD23 displays significant homology with Ca(2+)-dependent (C
      type) animal lectins, suggested the existence of natural ligands other than IgE.
      The recent finding that CD23 interacts with CD21, CD11b and CD11c indicates that
      CD23 should be viewed not only as a low affinity IgE receptor but also as an
      adhesion molecule involved in cell-cell interaction. After a brief overview of
      the molecular structure, there follows a discussion of the biological activities
      ascribed to human CD23.

PMID- 9651789
TI  - CD23/Fc epsilon RII: signaling and clinical implication.
AB  - CD23 is an activation antigen expressed by various human hematopoietic cells,
      tissular epithelial cells and represents the major low affinity receptor for IgE
      (Fc epsilon RII). In its membrane and soluble forms, CD23 has multiple ligands
      that enable this molecule to trigger various functions in human and murine cells.
      In this issue, we discussed the intracellular signaling events induced by soluble
      CD23 and the ligand involved in each target cell. Signal transduction through
      surface CD23 ligation is linked to cyclic nucleotides and nitric oxide (NO)
      pathways in various human cells and in rat macrophages. Recent in vivo data
      suggest a regulatory role for these signals during various human
      physiopathological situations such as hemopoiesis, anti-tumoral defense,
      inflammation, allergy, microbicidal activity of macrophages and eosinophils, skin
      disease, and HIV infection.

PMID- 9651790
TI  - Fc receptors as targets for immunotherapy.
AB  - Human membrane and soluble Fc epsilon receptors (Fc epsilon RI, Fc epsilon
      RII/CD23) and Fc gamma receptors (Fc gamma RI/CD64, Fc gamma RII/CD32, Fc gamma
      RIII/CD16) have been implicated in a number of diseases. Their functional roles
      such as capture and clearance of immune complexes, antibody-dependent cell
      cytotoxicity, or cytokine or inflammatory mediator release, make them potential
      targets for immuno-intervention. In the present review, we will describe how
      membrane and soluble human Fc epsilon R and Fc gamma R have been already used as
      targets/tools for immuno-interventions by using monoclonal and bispecific
      engineered antibodies. Some therapeutic uses of these molecules both in cancer,
      infectious, and auto-immune diseases are presented.

PMID- 9651791
TI  - Functions of Fc receptors on human dendritic Langerhans cells.
AB  - Immature dendritic cells are antigen presenting cells highly specialized for
      capturing and processing foreign protein antigens. These cells express Fc gamma
      RII and Fc epsilon RI which, by their ability to internalize and use the
      endocytic pathway, increase their capacity to process antigens. Immature
      dendritic cells, such as epidermal Langerhans cells, also release soluble forms
      of Fc gamma RII. These latter molecules are likely to compete with the membrane
      associated Fc gamma R to diminish or abrogate the capacity of dendritic cells to
      present immune complexes, as suggested by our in vitro experiments using both
      human and mouse epidermal Langerhans cells. However, when dendritic cells mature
      in vitro and become efficient stimulators of resting T cells, they rapidly down
      regulate and sometimes completely abolish the expression of their membrane
      associated Fc gamma R and Fc epsilon RI. Consequently, they lose or at least
      strongly diminish their capacity to capture immune complexes. At this stage, the
      release of soluble Fc gamma R by dendritic cells is also markedly diminished. One
      can hypothesize that the membrane-associated Fc gamma RII and the soluble Fc
      gamma RII are molecules expressed when dendritic cells are potent capturing and
      processing cells, the soluble Fc gamma RII molecule acting by competition as a
      negative regulatory element on the Fc gamma RII-mediated internalization of IgG
      containing immune complexes. Thus, the expression of membrane-associated Fc gamma
      R and Fc epsilon RI, as well as the release of soluble Fc gamma R, would seem to
      characterize the immature stage of dendritic cells.

PMID- 9651792
TI  - What health professionals can do to identify and resolve patient dissatisfaction.
AB  - BACKGROUND: Patient satisfaction affects consistency of self-care, health
      outcomes, level of service utilization, choice of health professionals, and
      decisions to sue in the face of adverse outcomes. Understanding patients'
      specific dissatisfactions may help health professionals and administrators
      identify and rectify organizational deficiencies before they become costly.
      COMMON CAUSES OF COMPLAINTS: As part of a series of research projects, more than
      12,000 patient/family complaint narratives were examined in which patients or
      patients' family members told interviewers or patient advocates about the care
      they received from their health professionals in both inpatient and outpatient
      settings. Complaints may be categorized as involving issues of care and
      treatment, communication, humaneness, access and availability, environment, and
      billing/payment. STRATEGIES FOR RESOLVING COMPLAINTS: Even though caregivers may
      not have control over all the factors that lead to dissatisfaction, they can
      often hear and address complaints. As a result, they may not only contribute to
      quality of care but improve the systems in which they practice. The challenges
      are how to prevent dissatisfaction in the first place, and, if it does occur, to
      identify and if possible rectify patient concerns. Three case studies are
      provided. CONCLUSION: All health professionals must be involved in efforts to
      resolve problems that compromise patient care. Some problems could be prevented
      if administrators and leaders used complaint data to recommend new policies and
      procedures or to identify and counsel with health care team members who generate
      disproportionate numbers of complaints. If all are involved in both prevention
      and problem solving, resources devoted to uncovering, understanding, and
      resolving patient complaints are likely to prove cost-effective.

PMID- 9651793
TI  - Using a hospitalwide performance improvement process for patient education
      documentation.
AB  - BACKGROUND: Decreases in length of hospital stay have increased pressure on staff
      to provide appropriate patient education. A hospitalwide continuous quality
      improvement (CQI) program was implemented to improve patient education
      documentation at Raritan Bay Medical Center (RBMC; Perth Amboy, NJ). IMPROVING
      THE PATIENT EDUCATION DOCUMENTATION PROCESS: In March 1995 the patient education
      committee was given the responsibility to develop a CQI program to improve
      documentation of patient education. Patient interviews revealed that assessment
      of patients' initial knowledge was inadequate and goal setting was omitted. The
      committee developed generic and disease-specific patient education documentation
      forms for educational assessment and patient education. The patient chart was
      reconfigured to include a central location for patient education. RESULTS: A
      review of almost 900 patient records established that the percentage of records
      on which patient education was documented had improved from 41% in summer 1995 to
      93% in fall 1996, with an improvement across all disciplines. A follow-up review
      in fall 1997 of 136 randomly chosen records indicated a slight decrease in rate
      of documentation of content areas, although nursing services and nutritional care
      continued to maintain their patient documentation education at a rate of > or =
      90%. DISCUSSION: Factors such as providing continuous feedback on patient
      education documentation performance to all nursing units and disciplines
      involved, developing additional disease-specific education assessment
      plans/documentation tools through an interdisciplinary process, and improving the
      data collection tool after each measurement period all contributed to improved
      patient education documentation. CONCLUSIONS: Patient education is now truly
      integrated at RBMC, with every pertinent discipline involved in decision making
      throughout the process of continuously improving the patient education process
      and documentation.

PMID- 9651794
TI  - The "door-to-needle blitz" in acute myocardial infarction: the impact of a CQI
      project.
AB  - BACKGROUND: A continuous quality improvement (CQI) project was conducted at
      Soroka Medical Center in Beer-Sheva, Israel, in an effort to identify and address
      causes of delays in thrombolytic therapy in patients arriving at a high-volume
      (160,000 patients per year) emergency department with acute myocardial infarction
      and thereby reduce the "door-to-needle time" (DTNT). The study had four phases:
      preintervention survey, peri-intervention process redesign, postintervention
      evaluation, and follow-up evaluation. CQI TEAM: The CQI team followed a seven
      step protocol: problem definition, present-state screening, factors analysis,
      solution development, outcome evaluation, standardization, and conclusions.
      RESULTS: A DTNT of 45 minutes was considered acceptable for this data set, and
      accordingly, patients were divided into an "early" group (n = 50, DTNT < 45
      minutes), and a "late" group (n = 50, DTNT > or = 45 minutes). After the CQI
      intervention, the mean DTNT decreased from 61.8 +/- 32.5 (mean +/- standard
      deviation) to 47.6 +/- 18.5 minutes (p < 0.029). The prolonged DTNT time
      intervals of the late versus the early groups was primarily due to extended
      decision-making time (36.0 +/- 22.7 versus 13.6 +/- 6.7 minutes, p < 0.003),
      followed by time until therapy was initiated (26.2 +/- 14.2 versus 11.1 +/- 5.8
      minutes, p < 0.002). CONCLUSIONS: Results suggest that the 30-minute DTNT
      suggested by the American College of Cardiology/American Heart Association is
      appropriate for patients with a clear diagnosis and no contraindications for
      thrombolysis, but when the risk-benefit ratio of thrombolytic therapy raises
      concerns, a 45- to 60-minute DTNT may still be acceptable. Further CQI projects
      should address technical triage of simple cases and clinical estimation of risk
      benefit ratio in complicated patients.

PMID- 9651795
TI  - Long-term follow-up in the Peer Assessment Program for nonspecialist physicians
      in Ontario, Canada.
AB  - BACKGROUND: The College of Physicians and Surgeons of Ontario has assessed
      randomly selected physician office practices since 1972. Each assessment consists
      of a tour of the premises and a review of a random selection of 20 to 30 medical
      records to evaluate the system of record keeping and the content of the records
      and to thereby indicate the quality of the physician's examinations, history
      taking, diagnosis and management plan. About 12% of nonspecialist physicians who
      need help to improve their records and/or the care they provide are identified
      annually, and following an interview with peers and simple educational
      interventions, more than 75% are successful in improving. METHODS: A follow-up
      was conducted to assess physician practices an average of six years after the
      first intervention. The reviewers were blinded as to whether the physician being
      reviewed had been reviewed previously. Each revisited physician was matched to
      three others undergoing their initial assessments in the same year. The matching
      variables were age, sex, school of graduation (Canadian versus other), rural
      versus urban practice location, and affiliation status with the College of Family
      Physicians of Canada. The assessed performance of the two groups was compared.
      RESULTS: The performance of the revisit group was significantly better than that
      of the matched group (p = 0.05). CONCLUSIONS: The assessment, interview, and
      educational interventions undertaken by the licensing authority produced an
      improvement in practice in the short term in the bottom 10%-15% of all physicians
      reviewed, which was sustained for more than six years.

PMID- 9651796
TI  - Insulin decreases skeletal muscle cAMP-dependent protein kinase (PKA) activity in
      normal monkeys and increases PKA activity in insulin-resistant rhesus monkeys.
AB  - Insulin activation of skeletal muscle glycogen synthase and glucose disposal is
      defective in both prediabetic and diabetic primates. Reduction in the activation
      of glycogen synthase by insulin could be the cause of lower glucose disposal
      rates, and could be the result, at least in part, of the failure of insulin to
      inhibit cAMP-dependent protein kinase activity (protein kinase A, PKA). To
      examine this proposed mechanism, PKA activity was measured in skeletal muscle
      (vastus lateralis) samples freeze-clamped in situ under basal fasting conditions
      before, and again during a euglycemic hyperinsulinemic clamp in 27 rhesus
      monkeys. Nine of the monkeys were normal (normal fasting glucose and insulin),
      eight were prediabetic (normal fasting glucose and hyperinsulinemia) and ten had
      spontaneous non-insulin-dependent diabetes (hyperglycemia). Insulin lowered PKA
      activity ratio in normal monkeys (basal vs insulin-stimulated, 14.4 +/- 3.2 vs
      8.1 +/- 1.8%, p < 0.05), but raised PKA activity ratio in prediabetic monkeys
      (5.4 +/- 1.4 vs 10.5 +/- 2.6%, p < 0.05). PKA activity ratio was unaffected by
      insulin in the diabetic monkeys (6.7 +/- 1.8 vs 7.5 +/- 1.4%). Basal PKA activity
      ratio was higher in normal monkeys compared to prediabetic (p < 0.05) and
      diabetic monkeys (p < 0.05). Basal PKA activity ratio was inversely related to
      the insulin-stimulated change in PKA activity ratio (r = -0.72, p < 0.001). We
      conclude that in vivo insulin during euglycemic hyperinsulinemic clamp decreases
      skeletal muscle PKA activity ratio in normal monkeys but fails to decrease the
      activity ratio of PKA in insulin resistant (prediabetic and diabetic) monkeys.
      The insulin resistant state is characterized by low basal fasting skeletal muscle
      PKA activity ratio.

PMID- 9651797
TI  - Temporal effect of methyl parathion on ovarian compensatory hypertrophy,
      follicular dynamics and estrous cycle in hemicastrated albino rats.
AB  - Methyl parathion, an organophosphorus pesticide, was administered i.p. at a dose
      of 5 mg/kg body weight to hemicastrated virgin rats for 1, 5, 10 and 15 days.
      Treatment with methyl parathion for 1 and 5 days revealed no change in the
      ovarian weight with -0.64% and -9.63% hypertrophy respectively and no change in
      healthy and atretic follicles when compared with hemicastrated oil-treated
      controls. However, treatment with methyl parathion for 10 and 15 days resulted in
      a significant decrease in ovarian weight gain with -21.36% and -31.98%
      hypertrophy, respectively, a significant decrease in the number of healthy
      follicles, and no change in the number of atretic follicles. The number of
      estrous cycles and duration of each phase of the estrous cycle were significantly
      affected with methyl parathion treatment for 5, 10 and 15 days. However, there
      were no significant changes in the number of estrous cycles and duration of
      estrus and metestrus phases in 1 day methyl parathion treatment except for a
      decrease and increase in proestrus and diestrus phases respectively. The weight
      of the uterus was significantly decreased whereas those of the liver, kidney and
      adrenal did not change in any of the methyl parathion treated groups.

PMID- 9651798
TI  - Rat aorta and mesenteric artery respond differently to serotonin.
AB  - The sensitivity (EC50) of the ring segment of the mesenteric artery to serotonin
      (4.84 +/- 0.53 x 10(-7) mol.l-1) was 17x greater than that of the aortic ring
      segment (5.29 +/- 0.46 x 10(-6) mol.l-1). Incubation of the ring segments in
      physiological salt solution (PSS) containing methylene blue greatly potentiated
      the sensitivity of both the aorta and mesenteric artery to serotonin. The degree
      of potentiation was higher in the aorta than mesenteric artery. L-NAME also
      increased the sensitivity of both the aorta and mesenteric artery to serotonin
      and there was no difference in the degree of potentiation of the responses
      between the aorta and the mesenteric artery. Indomethacin inhibited the
      contractile responses of the aorta and the mesenteric artery to serotonin.
      Phenoxybenzamine reduced the contractile responses of both the aorta and the
      mesenteric artery by the same magnitude. Captopril (10(-4) mol.l-1) significantly
      attenuated the responses of the mesenteric artery more than the aorta, while
      methysergide (10(-8) mol.l-1) completely abolished the difference in the
      responses (EC50 for aorta = 3.50 +/- 0.55 x 10(-5) mol.l-1 vs 5.00 +/- 0.49 x 10(
      5) mol.l-1 for mesenteric artery). This study demonstrates that rat aorta and
      mesenteric artery respond differently to serotonin and the differential response
      is due to a methylene blue sensitive factor and differences in either the
      receptor population or sensitivity.

PMID- 9651799
TI  - The effect of antioxidant vitamins E and C on lipoperoxidation of erythrocyte
      membranes during hyperbaric oxygenation.
AB  - The aim of this research was to determine whether administration of an
      antioxidant vitamin combination can reduce oxidative damage in erythrocytes
      induced by hyperbaric oxygenation (HBO). Malonyldialdehyde (MDA) levels and
      osmotic fragility ratios in erythrocytes of 28 rats were compared in group A
      [control], group B [Vitamin (E + C)], group C [HBO] and group D [HBO + Vitamin (E
      + C)]. HBO was applied at a pressure of 2.8 atmospheres absolute (ATA), 1 hour
      daily, for 45 days in groups C and D. Administration of alpha-tocopherol acetate
      (40 mg/kg) and Na-ascorbate (200 mg/kg) was initiated 3 days before the start of
      HBO exposures and administered intraperitoneally 3 times a week for 45 days. MDA
      levels and osmotic fragility ratios were significantly higher in group C than in
      groups A and B (p < 0.05 for all). Significant decreases in MDA levels and
      osmotic fragility were observed in group D compared with group C, although these
      parameters were still significantly higher than in controls (p < 0.05 for all).
      Prolonged HBO resulted in oxidative damage indicated by significant increases in
      MDA levels and osmotic fragility ratios, which were reduced by concomitant
      vitamin (E + C) administration.

PMID- 9651800
TI  - Effect of chloroquine on the contractility of the smooth muscles of the rat
      uterus, trachea and urinary bladder.
AB  - This study was performed to investigate the effect of chloroquine (CQ) on the
      contractility of isolated smooth muscles of the rat uterus, urinary bladder; and
      trachea. Chloroquine, 4 x 10(-4) mol.l-1 completely abolished uterine
      contractions produced by 10(-2) IU/ml oxytocin, and 10(-6) mol.l-1 5
      hydroxytryptamine (5-HT) and acetylcholine (Ach). Chloroquine also caused a
      concentration-dependent relaxation of 10(-6) mol.l-1 Ach-contracted rat trachea.
      Cumulative addition of CQ (10(-8)-10(-3) mol.l-1) to spontaneously contracting
      rat urinary bladder did not produce any significant effect. It also did not
      affect the contractile response of the bladder to Ach and 5-HT. The results
      suggest that CQ inhibits the contractile process in the rat uterus and trachea
      but not the urinary bladder.

PMID- 9651801
TI  - On the mechanisms of adenosine induced pulmonary vasoconstriction in rats.
AB  - The effect of adenosine on pulmonary vessels was studied in isolated perfused rat
      lungs. Drugs were administered intra-arterially in a fixed volume of 0.1 ml Krebs
      solution as bolus injections. Adenosine responses were obtained before and 10 min
      after drug injections. When applied in logarithmically increasing doses (1-100
      micrograms/ml), adenosine caused dose-dependent increases in pulmonary perfusion
      pressure (e.g. pulmonary vasoconstriction) which were readily reversible.
      Challenging adenosine with quinidine, dihydroergocristine and cyproheptadine (2
      micrograms/ml each) did not significantly alter adenosine responses. Pretreatment
      of lungs with 0.5 mM theophylline, 10 micrograms/ml indomethacin, 30
      micrograms/ml tebokan (a PAF antagonist) or 1 microgram/ml methylene blue for 10
      min, however, antagonized the vasoconstrictor effect of the drug significantly.
      From these experiments, it was concluded that the mechanisms underlying the
      pulmonary vasoconstrictor action of adenosine are complex, and that both types of
      purinoceptors, prostaglandins, PAF and other vascular endothelial hormones might
      be involved.

PMID- 9651802
TI  - Neuron degeneration induced by verapamil and attenuated by EGb761.
AB  - Calcium channel blockers are used as neuroprotective agents, as glutamate
      antagonists. However, it has been found that calcium channel blockers may
      compromise neuronal survival after long-term exposure. To explore the mechanisms
      of the toxicity of calcium channel blockers on neurons, we studied the
      morphological characteristics and biochemical changes of cultured cortical
      neurons treated with verapamil, a calcium channel blocker. We now report that
      cerebral cortical cultures exposed to verapamil for 48 h undergo neuronal
      degeneration in both concentration-dependent and time-dependent fashion, possibly
      partially through the activation of apoptosis. On the other hand, it was found
      that Ginkgo biloba extract (EGb761) attenuated verapamil-induced neuronal injury,
      suggesting the possibility of using verapamil combined with EGb761 clinically.
      Furthermore, both B-50 immunoactivity (BIA) and the concentration of
      intracellular calcium in single neurons ([Ca2+]i) decreased after a 48-h exposure
      to verapamil, suggesting that the mechanisms of verapamil-induced degeneration
      may be associated with the disruption of intracellular calcium homeostasis and
      the inhibition of normal axonal elongation.

PMID- 9651803
TI  - Pathological studies on camelpox lesions of the respiratory system in the United
      Arab Emirates (UAE).
AB  - Three dromedary camels (Camelus dromedarius), which died from generalized
      camelpox with lesions in the respiratory system, were investigated.
      Histopathological lesions in the lung consisted of small, sometimes confluent
      foci of proliferated bronchial epithelium, necrosis and fibrosis. Orthopoxvirus
      cameli was demonstrated in all three cases by transmission electron microscopy
      and the virus was isolated from the lung and trachea on Dubca cells. It was
      proved by restriction enzyme analysis of the viral DNA that the isolates were
      identical. Immunohistochemical examination showed numerous poxvirus antigen
      positive cells in the bronchial epithelia. Immunolabelled material was found in
      bronchial epithelial cells with hydropic degeneration and in infiltrating
      macrophages.

PMID- 9651804
TI  - The pathogenesis of experimental neosporosis in pregnant sheep.
AB  - Three groups of eight pregnant sheep were inoculated with tachyzoites of the NCl
      isolate of Neospora caninum at 45 (group 1), 65 (group 2) or 90 (group 3) days'
      gestation. A further six animals (group 4) served as controls. Fourteen of the
      infected ewes developed a fever, which in two cases was biphasic. In six ewes in
      group 1, the fetuses died and were resorbed, and in the other two the fetuses
      were aborted. In group 2, one ewe resorbed her fetus, six aborted dead fetuses
      and one produced a live lamb. In group 3, six ewes aborted and two produced one
      live and one stillborn lamb each. Thus, the stage of gestation influenced the
      outcome of infection. All but one of the ewes "seroconverted", as shown by enzyme
      linked immunosorbent assay, and 10 of 13 fetal sera examined by an indirect
      immunofluorescent antibody test were positive. The polymerase chain reaction was
      also used to detect DNA of N. caninum in aborted tissues. Immunohistochemical
      examination showed that the parasite had invaded the placentas of all cases
      examined, displaying an apparent predilection for fetal chorionic epithelium and
      fetal placental blood vessels, as well as inducing thrombosis in some maternal
      caruncular blood vessels. Organisms were associated with fetal vasculitis, focal
      degeneration and inflammation of the chorioallantois, and widespread, severe
      focal necrosis in the placentome. Characteristic lesions were seen in the fetal
      brains, in addition to focal leucomalacia, thought to be due to anoxia resulting
      from the placental damage. The six control sheep in group 4 remained clinically
      healthy and produced normal uninfected lambs.

PMID- 9651805
TI  - Morphometric analysis of bovine lymphomas classified according to the National
      Cancer Institute Working Formulation.
AB  - The National Cancer Institute Working Formulation (NCI-WF) for the subjective
      classification of human non-Hodgkin's lymphoma is readily applicable to the
      classification of bovine lymphomas. Forty-nine cases of bovine lymphoma were
      analysed morphometrically to see if nuclear size and cleavage were distributed
      continuously or discretely between different NCI-WF tumour cell types. The mean
      nuclear area (+/- standard error of the mean, SE) was significantly greater (P <
      10(-6)) in cells from the different types of diffuse large-cell lymphoma than in
      cells from the different types of small-cell lymphoma (42.91 +/- 1.21 micron 2 vs
      19.33 +/- 1.08 micron 2, respectively); there was no overlap between the two
      groups. The mean nuclear are (+/- SE) of cells from diffuse large-cell lymphomas
      was significantly greater (P < 10(-4)) than that of cells from small non-cleaved
      lymphomas (42.74 +/- 1.72 micron 2 vs 27.54 +/- 1.08 micron 2, respectively), and
      there was again no overlap between the two groups; these two cell types are
      difficult to distinguish by any criteria other than size. Additionally, the cell
      to-cell variability in nuclear area within a given tumour was significantly
      greater (P < 0.001) for the diffuse large-cell type than for the small non
      cleaved cell type. The mean nuclear form factor (+/- SE) and mean nuclear contour
      indices (+/- SE) of the diffuse large cleaved cell type (0.53 +/- 0.02 and 5.08
      +/- 0.11, respectively) were significantly different (P < 0.01 to 10(-6)) from
      the same parameters in the diffuse large-cell type (0.82 +/- 0.01 and 3.94 +/-
      0.04, respectively). Some of the major criteria of the NCI-WF used subjectively
      to discriminate between bovine lymphoma cell types were supported by morphometric
      measurements. The magnitude of the differences in nuclear morphological
      characteristics between bovine lymphoma cell types was such that there was no
      overlap.

PMID- 9651806
TI  - Pasteurella multocida infection in the chicken embryo.
AB  - Pasteurella multocida infection in embryonated chicken eggs was studied by chorio
      allantoic membrane inoculation. Strain differences were demonstrated in terms of
      lesion severity and time to death, especially during the first 24 h post
      inoculation. A strain of low virulence gave a clear dose response but more
      virulent strains did not. Comparable results were obtained by infecting 6-week
      old chickens. The main lesions in inoculated embryos appeared as severe vascular
      involvement of the entire embryo and feather tracts, thickening of the chorio
      allantoic membrane, and enlargement and congestion of the yolk sac. The bacteria
      were demonstrated by transmission electron microscopy, either extracellularly or
      multiplying intracellularly in hepatocytes, heart tissue, and in the hyperplastic
      layer of the chorio-allantoic membrane, with resulting damage to the cellular
      organelles, and severe tissue changes.

PMID- 9651807
TI  - Spontaneous tumours in tree shrews (Tupaia belangeri): population studies.
AB  - In a necropsy series at the German Primate Centre, 63 of 1132 tree shrews were
      found to have tumours. The youngest affected animal was < 6 months old, but the
      incidence of tumours increased strikingly beyond 2 years of age; of 17 animals
      aged > 8 years, no less than 14 (82.4%) were affected. The sites of neoplasia
      were the genital system (22 cases), haematopoietic system (18 cases of malignant
      lymphoma, many involving the digestive tract), lungs (14 cases), integument (five
      cases), digestive tract (three cases other than those with malignant lymphoma)
      and urinary bladder (one case).

PMID- 9651808
TI  - Myocardial contraction band necrosis in stranded cetaceans.
AB  - The term contraction band necrosis describes focal hypercontraction and lysis of
      small groups of myocardial cells. Contraction band necrosis of the myocardium was
      identified in 100% of 52 whales and dolphins (cetaceans) stranded along the
      western coast of the Gulf of Mexico between April 1991 and November 1996. The
      myocardial lesions in the cetaceans were identical, both grossly and
      histologically, to those previously described in man and other animals. Such
      lesions may contribute to the high mortality rate in stranded cetaceans.

PMID- 9651809
TI  - Immunohistochemical demonstration of spread of Aujeszky's disease virus to the
      porcine central nervous system after intestinal inoculation.
AB  - Aujeszky's disease virus (ADV) was injected into the duodenal lumen of eight
      specific pathogen-free pigs aged 5 weeks. The infected pigs did not show any
      diarrhoea or nervous symptoms, but they developed characteristic necrotizing
      enteritis and myenteric plexitis, accompanied by follicular necrosis in the
      Peyer's patches. ADV antigen was detected in the submucosa of the dome area of
      Peyer's patches, lymphatic follicles, Meissner's and Auerbach's plexuses, solar
      ganglia and thoracic spinal ganglia. These findings suggest that ADV spreads from
      the intestinal mucosa to the central nervous system via the autonomic nerves.

PMID- 9651810
TI  - In-vitro studies on mechanisms of immunosuppression associated with bovine
      respiratory syncytial virus.
AB  - Bovine respiratory syncytial virus (BRSV) depressed the proliferative reactivity
      of normal ovine peripheral blood lymphocytes to phytohaemagglutinin (PHA). This
      BRSV-induced reduction in proliferative reactivity was not reversed or
      ameliorated by the addition of (1) indomethacin or flunixin meglumine, substances
      known to inhibit the production of prostaglandins, or (2) the cytokines,
      interleukin-1 (IL-1) and interleukin-2 (IL-2), or (3) rat growth factor. The
      results suggest that the suppression of ovine lymphocyte reactivity to PHA
      associated with BRSV was not caused by the release of cyclooxygenase products
      such as prostaglandins, or the production of inhibitors of IL-1 or IL-2.

PMID- 9651811
TI  - The effects of bovine respiratory syncytial virus on the phagocytic and antigen
      presenting capacity of peripheral blood monocytes and monocytic cell lines
      derived from lambs and calves.
AB  - Human respiratory syncytial virus and bovine respiratory syncytial virus (BRSV)
      suppress lymphocyte responses to mitogens. In the present study, the possible
      effects of BRSV on some functions of antigen-presenting cells (APC) were
      investigated by exposing ovine monocytic cells to the virus before their use as
      APC. The depletion of monocytes from peripheral blood mononuclear cells resulted
      in the near total abrogation of proliferative responses to phytohaemagglutinin
      (PHA). Reactivity was restored by the addition of homologous monocytic cells
      derived from ovine peripheral blood monocytes as APC. The exposure of these
      monocytic cells to BRSV for 48 h before their use as APC significantly reduced
      the proliferative responses of uninfected ovine lymphocytes to PHA. Furthermore,
      the exposure of bovine peripheral blood monocytes and bovine and ovine monocytic
      cell lines to BRSV for 48 h reduced their capacity to phagocytize latex beads.

PMID- 9651812
TI  - The carriage of Pasteurella haemolytica in sheep and its transfer between ewes
      and lambs in relation to mastitis.
AB  - The possible presence of Pasteurella haemolytica in the mouth of lambs and on the
      skin of the teats of ewes was investigated. The organism was found in the mouth
      of ewes and lambs and, soon after lambing, on the teat skin of ewes. It was not
      isolated from the teat skin of pregnant ewes 1-14 days before lambing or from the
      teat skin one week after the lambs had been weaned. The transfer of P.
      haemolytica to the teat skin is undoubtedly mediated by the lamb. There is ample
      opportunity for the teat orifice to be exposed to P. haemolytica during the
      suckling period and it is known that only a few colony-forming units of virulent
      organisms are required to initiate mastitis.

PMID- 9651813
TI  - Evaluation of day-old specific pathogen-free chicks as an experimental model for
      pathogenicity testing of intestinal spirochaete species.
AB  - Specific pathogen-free chicks aged 1 day were challenged per os with strains of
      five different species of intestinal spirochaete originally isolated from pigs or
      human beings. A virulent strain of Serpulina hyodysenteriae (WA 15) colonized
      chicks, causing retarded growth rate and histological changes, including caecal
      atrophy, epithelial and goblet cell hyperplasia, and crypt elongation. A further
      strain of S. hyodysenteriae (SA3), which was apparently avirulent for pigs, and a
      strain of Serpulina intermedia (889) colonized fewer chicks, caused less severe
      lesions and did not significantly depress growth rate. Strains of Serpulina
      murdochii and Brachyspira aalborgi failed to colonize or cause histological
      changes. Four strains of Serpulina pilosicoli (Kar, Rosie-2299 and GAP 401,
      isolated from human beings, and 3295, isolated from a pig) colonized chicks, and
      large numbers showed polar attachment to the caecal epithelium; all strains,
      apart from Rosie-2299, caused watery diarrhoea and wet litter, but did not
      significantly retard growth. Variation both in the degree of spirochaetal
      attachment and the resulting development of lesions was observed between S.
      pilosicoli strains as well as between individual chicks infected with the same
      strain. The study indicated that chicks may be useful in studying the
      pathogenicity of strains of S. hyodysenteriae, S. intermedia and S. pilosicoli.

PMID- 9651814
TI  - Effects of nicotine on peripheral cutaneous blood flow and skin temperature.
AB  - We hypothesized that if nicotine was used in a form that was not adulterated with
      other hazardous substances found in tobacco, it would increase cutaneous blood
      flow (CBF) resulting in an increase in skin temperature. The effects of nicotine
      on CBF was investigated in 80 healthy volunteers and 6 patients with peripheral
      circulation disturbances. Each subject was required to chew nicotine gum
      (containing 2 mg nicotine) for 15 min and the CBF was then measured with laser
      blood flowmetry. Skin temperature of 35 volunteers was measured with thermography
      before and after chewing the gum for 15 min. A control study was performed using
      ordinary gum without nicotine. Increased CBF (> or = + 1 ml/min/100 g) was
      observed in 55 of 86 subjects (64%, 33.7-38.6 ml/min/100 g, P < 0.01). An
      elevation in skin temperature (> + 0.1 degree C) was also observed with nicotine
      gum in 26 of 35 healthy subjects (74%, + 0.62 +/- 0.96 degree C, P < 0.001). The
      increase in CBF was greater in subjects in which the initial CBF was lower than
      in others (P < 0.01). Nicotine gum was found to increase CBF (55/86) and elevate
      skin temperature (26/35). The smaller the initial CBF value, the greater was the
      increase in CBF. Nicotine or nicotine derivatives might prove to be useful agents
      for the treatment of peripheral circulation disturbances.

PMID- 9651815
TI  - Analysis of mechanisms of epidermal proliferation induced by intracutaneous
      injection of cholera toxin by the use of site-specifically mutated cholera
      toxins.
AB  - Intracutaneous injection of cholera toxin (CT) into rabbits increases vascular
      permeability and induces epidermal proliferation. To understand the mechanisms of
      these effects on the skin, we evaluated the involvement of the ADP
      ribosyltransferase activity of the A subunit of CT and receptor-binding
      interactions between GM1-ganglioside and the B subunit of CT. We constructed two
      mutant CTs, E112K and W88K, by site-directed mutagenesis. Mutant CT-E112K, in
      which glutamic acid at position 112 (E112) of the A subunit of CT was replaced by
      lysine, has been shown to have lost its biological activity on Chinese hamster
      ovary (CHO) cells because of its abolished ADP-ribosyltransferase activity.
      Mutant CT-W88K, in which tryptophan at position 88 (W88) of the B subunit of CT
      was replaced by lysine, has been shown to have lost its binding ability to GM1
      ganglioside. Intracutaneous injection of these mutant CTs evoked less vascular
      permeability and less epidermal proliferation than recombinant wild-type CT.
      These results suggest that: (1) the ADP-ribosyltransferase activity carried by
      E112 of the A subunit of CT; and (2) the binding ability to GM1-ganglioside via
      W88 of the B subunit of CT are essential for these effects of CT on the skin.

PMID- 9651816
TI  - Interferon-gamma-dependent induction of manganese superoxide dismutase activity
      of SV40-transformed human keratinocytes by anti-Fas antibody and by TNF-alpha.
AB  - It has been reported that cellular oxidative stress induces apoptosis, that may
      be inhibited by scavengers of reactive oxygen intermediates (ROIs). Superoxide
      dismutase (SOD) is among the most active scavengers of ROIs, providing defense
      against the cellular oxidative stress. Fas antigen and tumor necrosis factor
      (TNF) receptor are the cell surface proteins, stimulation of which induces
      apoptosis of keratinocytes. Using SV40-transformed human keratinocytes (SVHK
      cells), we investigated the effects of anti-Fas antibody and TNF-alpha on the SOD
      activity. Treatment of SVHK cells with anti-Fas antibody or TNF-alpha in the
      presence of interferon-gamma (IFN-gamma) resulted in an increase in Mn-SOD
      activity, Cu,Zn-SOD activity was not affected. In the absence of IFN-gamma, no
      increase in Mn-SOD activity was detected. The induction of IFN-gamma-dependent Mn
      SOD activity by anti-Fas antibody or TNF-alpha was concentration-dependent; the
      maximal effect was observed at 1-10 micrograms/ml and 5-10 ng/ml, respectively.
      The increase in Mn-SOD activity was observed at 6 h following the treatment and
      remained for at least 48 h. Northern blot analyses showed that Mn-SOD mRNA
      increased within 3 h without a significant change in Cu,Zn-SOD mRNA. The addition
      of both anti-Fas antibody and TNF-alpha in the presence of IFN-gamma resulted in
      an additive increase in Mn-SOD activity. Although the addition of 12-o
      tetradecanoylphorbol-13-acetate (TPA) singly to the incubation medium had no
      effect on either Mn-, or Cu,Zn-SOD activity, it significantly augmented the IFN
      gamma-dependent induction of Mn-SOD activity by anti-Fas antibody or by TNF
      alpha. The protein kinase C inhibitor, 1-(5-isoquinoline-sulfonyl)-2-methyl
      piperazine dihydrochloride (H-7), significantly inhibited the TPA-dependent
      increase in Mn-SOD activity. These results indicate that the stimulation of Fas
      antigen or TNF receptor increases Mn-SOD activity of SVHK cells in the presence
      of IFN-gamma and that TPA augments the process through the activation of protein
      kinase C.

PMID- 9651817
TI  - Morphological, biochemical and molecular biological characteristics of a
      granulocyte colony-stimulating factor-producing human eccrine carcinoma cell
      line.
AB  - We describe here a newly established cell line from an eccrine carcinoma which
      produced an abundant amount of granulocyte colony-stimulating factor (G-CSF). An
      eccrine carcinoma of the scalp of a 69 year-old-Japanese female had metastasized
      to the pleura. Clinically, she had marked neutrophilia (up to 60,000/mm3), and a
      high level of G-CSF (38.7 x 10(3) pg/ml) was detected in the pleural effusion, as
      determined by enzyme-linked immunosorbent assay (ELISA). We established a cell
      line in vitro and maintained the cells in culture for 30 months in 90
      subcultures. We investigated whether these tumor cells were able to produce G-CSF
      in culture and found that they were. We also found that the amount of G-CSF
      produced paralleled the rise in cell number (26.5 x 10(3) pg/ml at confluency).
      When culture media were administered to rabbits (25 ml/rabbit), the amount of
      circulating neutrophils increased until the number was equal to or greater than
      that resulting from injection of recombinant human G-CSF (rhG-CSF)(75
      micrograms). This effect persisted for 7 days. When tumors were induced in SCID
      and nude mice by injecting cultured cells (1 x 10(7) cells/mouse), the number of
      circulating neutrophils also correlated well with tumor size in these mice
      (200,000/mm3, 3 cm tumor). After tumor removal, the neutrophil number returned to
      normal within 30 days. G-CSFmRNA in cultured, cells was detected by RT-PCR. Based
      on these results, it was confirmed that the marked neutrophilia observed in the
      patient was caused by the tumor-generated G-CSF. This is the first G-CSF
      producing cell line developed from a cancer of the skin.

PMID- 9651818
TI  - Further characterization of a new in vitro angiogenesis model under serum free
      culture conditions; suppression of endothelial cell differentiation by serum.
AB  - We studied the regulation of the extracellular matrix in the recently established
      murine vascular endothelial cell clones, F-2 or F-2C. F-2 cells constitutively
      show a cobblestone growth pattern under serum supplemented culture conditions,
      whereas F-2C cells undergo spontaneous histodifferentiation to form tubular
      structures in chemically defined media. We reported that the tubulogenesis
      induced by F-2C might relate to the heavy deposition of a 'basement membrane
      analog' as a subendothelial matrix (SEM). We further characterized the regulation
      of extracellular matrix (ECM) metabolism in these cell clones, in terms of
      gelatinase expression, ECM degradation and the effects of serum. F-2C cells in
      culture medium containing 1% serum did not undergo tubulogenesis but presented
      cobblestone growth. Zymography analysis showed that both F-2 and F-2C cells
      express two gelatinase (72 and 92 kDa). However, F-2 cells mainly expressed the
      former and faintly the latter, whereas F-2C mainly expressed the latter.
      Proteolysis studies showed that the spent media conditioned by F-2C cells
      partially cleaved type IV collagen and completely degraded type V collagen. The
      cleavage of type V collagen was suppressed by the addition of serum, whereas that
      of type IV collagen was not. The proteolysis of laminin and fibronectin by the
      conditioned medium was not observed. Serum-supplemented F-2 or F-2C cultures
      markedly suppressed SEM deposition. These results indicated that F-2C cells under
      serum free culture conditions not only present a simple and useful in vitro model
      with which to study the dynamic processes of proteolysis and ECM metabolism
      during the sequential phases of angiogenesis, but is also useful for analyzing
      the serum effects on angiogenesis (AG).

PMID- 9651819
TI  - Effects of various salts and irradiation with UV light on the attachment of
      Staphylococcus aureus strains.
AB  - We investigated the attachment of Staphylococcus aureus isolated from atopic
      dermatitis lesions to plastic tissue-culture coverslips. We found that attachment
      was weaker in (rabbit) plasma with 5 or 10% NaCl and in plasma with 5 or 10% sea
      salts than in the control plasma after incubation for 2 h (P < 0.01). The
      attachment was weaker still in plasma with 10% NaCl or 10% sea salts than in the
      control plasma after incubation for 24 h (P < 0.01). Plasma coagulation of four
      S. aureus strains isolated from atopic dermatitis lesions was not detected in
      plasma with 10% NaCl (pH 5.6) or 10% sea salts (containing 0.372% Mg2+) after
      incubation for 12, 24, 36 and 60 h. The attachment of S. aureus strain cells to
      the coverslip in plasma was weaker after irradiation with UVA at 25 or 50 J/cm2
      (P < 0.01) and UVB at 0.5 J/cm2 (P < 0.05) both of which are covered by a black
      cloth, than without irradiation after incubation for 24 h. Plasma coagulation was
      not detected after irradiation with UVA at 25 or 50 J/cm2 with a black cloth
      cover (temperature reached 50 degrees C), but was detected after UVA irradiation
      at the same doses combined with cooling (temperature reached 22 degrees C), after
      incubation for 24 h. The results suggest that the attachment of S. aureus cells
      isolated from atopic dermatitis lesions to the coverslip is suppressed in the
      presence of 10% salts and irradiation with UVA and UVB, and that plasma
      coagulation of S. aureus cells isolated from atopic dermatitis lesions is
      suppressed in the presence of 10% salts, irradiation with UVA, and heating.

PMID- 9651820
TI  - Modulation of UVA light-induced oxidative stress by beta-carotene, lutein and
      astaxanthin in cultured fibroblasts.
AB  - The ability of beta-carotene, lutein or astaxanthin to protect against UVA
      induced oxidative stress in rat kidney fibroblasts (NRK) was assessed. Activities
      of the antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD), and
      changes in thiobarbituric acid reactive substances (TBARS) were measured as
      indices of oxidative stress. Exposure to UVA light at a dose intensity of 5.6
      mW/cm2 for 4 h resulted in a significant decrease in CAT and SOD activities and a
      significant increase in TBARS. No cytotoxicity, as indicated by lactate
      dehydrogenase (LDH) release, was observed. beta-Carotene (1 microM), lutein (1
      microM) and astaxanthin (10 nM) protect against UVA light-induced oxidative
      stress in vitro with astaxanthin exhibiting superior protective properties.

PMID- 9651821
TI  - The relationship between the psychological and immunological state in patients
      with atopic dermatitis.
AB  - The relationship between the psychological and immunological state in patients
      with atopic dermatitis was investigated. It was found that patients with atopic
      dermatitis are significantly more depressive and scored higher for state anxiety
      (P < 0.05) than the normal control group. They also tended to be more
      psychosomatic symptom-prone and to score higher for trait anxiety. NK activity in
      patients with atopic dermatitis was significantly lower than in normal controls
      (P < 0.01), while serum IFN-gamma levels tended to be slightly higher and serum
      IL-4 levels somewhat lower. No significant correlation was detected between any
      pair of psychological test/immunological examination for either patients or
      normal controls. However, in the examination of path analyses, psychological
      variables affect serum levels of IFN-gamma and IL-4 more in the patients than the
      normal controls. Only STAI(T) and (S) affect NK activity in atopic dermatitis
      patients. By a discriminant analysis, NK cell activity and serum IFN-gamma
      appeared statistically significant. We conclude that the psychological state is
      to some extent related to the immunological state.

PMID- 9651822
TI  - The pathogenesis of squamous cell cancer: lessons learned from studies of skin
      carcinogenesis.
AB  - This study used the induction of squamous cell carcinomas on mouse skin as an
      experimental model to evaluate molecular and biochemical changes that contribute
      to the neoplastic phenotype. The study was facilitated by the development of
      keratinocyte cell culture assays that reproduce each stage of the carcinogenesis
      process, by discoveries of stage-specific genetic and epigenetic changes and by
      application of pharmacological and molecular tools that modify each step. An
      early event in the transformation of keratinocytes involves mutation and
      activation of the rasHa gene, producing a benign tumor. The phenotypic
      consequences of ras mutations are mediated by activation of the epidermal growth
      factor receptor (EGFR), upregulation of protein kinase C (PKC) alpha and AP-1
      mediated transcriptional activity and inactivation of PKC delta through tyrosine
      phosphorylation. These changes in benign tumors are manifested by
      hyperproliferation (EGFR), aberrant expression of keratinocyte genes (PKC alpha
      and AP-1) and delayed terminal differentiation (PKC delta). Accumulated
      chromosomal abnormalities, multifocal phenotypic changes and alterations in gene
      expression are associated with premalignant progression. Upregulation of the fos
      gene and AP-1 transcriptional activity causes malignant conversion of benign
      keratinocytes. In the absence of c-fos, benign tumor cells fail to upregulate
      secreted angiogenic and proteolytic factors and this may prevent malignant
      conversion. These pathways provide targets for preventive strategies to interrupt
      the process of carcinogenesis prior to the evolution of the fully malignant
      tumor.

PMID- 9651823
TI  - Repeated subcutaneous injection of staphylococcal enterotoxin B-stimulated
      lymphocytes retains epidermal thickness of psoriatic skin-graft onto severe
      combined immunodeficient mice.
AB  - Several approaches have recently been carried out to attempt to establish a mouse
      transplantation model of psoriasis. To study the effects of superantigen-driven
      peripheral blood mononuclear cells (PBMCs) on the persistence of psoriasiform
      epidermis and cytokine gene expression of the grafted psoriatic skin,
      staphylococcal enterotoxin B (SEB)-stimulated PBMCs (SEB-PBMCs) from psoriatic
      patients were subcutaneously injected once or repeatedly under the grafted full
      thickness involved psoriatic skin onto severe combined immunodeficient (SCID)
      mice. After 5 weeks, the persistence of a psoriasiform epidermis was most
      distinct in mice with repeated injection of SEB-PBMCs. E-selectin expression was
      observed on endothelial cells in the upper dermis in mice with repeated injection
      of both SEB-stimulated and unstimulated PBMCs, while mice with single injection
      of unstimulated or SEB-PBMCs did not show positive staining. Both interleukin-1
      beta (IL-1 beta) and interferon-gamma (IFN-gamma) mRNA were detected after 5
      weeks, only in mice with repeated injection of SEB-PBMCs. It is concluded that
      continuous supply of the activated PBMCs may help the persistence of psoriasiform
      architecture more clearly, and that this transplantation mouse model may serve as
      an in vivo model for the study of the pathogenesis and therapy of psoriasis.

PMID- 9651824
TI  - Biochemical and immunohistochemical analyses of keratin expression in basal cell
      carcinoma.
AB  - Recently we demonstrated that the keratin 17 (K17) content exceeded the K16
      content in most follicular tumors, in comparison with non-follicular epithelial
      skin tumours by two-dimensional gel electrophoresis (2-DE), densitometry and
      immunohistochemistry. At present the origin of basal cell carcinoma (BCC) is
      unknown. So, based on the above results, we studied keratin expression in eight
      cases of BCC, in order to analyze tumor differentiation by both biochemical and
      immunohistochemical methods. Biochemically, using 2-DE and immunoblotting,
      stratified epithelial keratins K5/K14 and large amounts of K17 were present in
      all cases. Simple epithelial keratins K8 and K19 were expressed in all and half
      of the cases, respectively. However, hyperproliferative associated keratins
      (K6/K16) and keratinized keratins (K1/K10) were detected in only a few cases.
      Immunohistochemical studies using frozen sections with chain-specific antikeratin
      monoclonal antibodies against K1, K7, K8, K10, K14, K16, K17, K18 and K19 showed
      that BCC tumor cells reacted positively with antibodies against K8, K14, K17 and
      K19, but did not react, or were rarely positive with K1, K7, K10, K16 and K18
      antibodies. Predominant expression of K17 and the frequent expression of K8 and
      K19, with little K6/K16 and K1/K10 expression are the characteristic features of
      BCC, suggesting that BCC is differentiated towards undifferentiated follicular
      epithelia, most probably hair bulge cells.

PMID- 9651825
TI  - Langerhans cells in prurigo nodularis investigated by HLA-DR and S-100
      immunofluorescence double staining.
AB  - The Langerhans cell is one of the antigen-presenting cells in the immune system.
      To study the presence of cutaneous Langerhans cells in prurigo nodularis, age-
      and sex-matched prurigo nodularis patients and healthy volunteer skin biopsies
      were investigated by an HLA-DR and S-100 immunohistochemical double staining
      method. The results showed that the HLA-DR- and S-100-immunoreactive (IR)
      Langerhans cells were altered in prurigo nodularis epidermis and dermis. The
      number of epidermal Langerhans cells in the prurigo nodularis patients was
      decreased in five and increased in two cases. In the dermis, the HLA-DR- and S
      100-IR cells were apparently more numerous than in the controls. In the involved
      skin there were also more S-100-IR coarse nerve fibres in the dermis as compared
      to controls. The results indicate that dermal Langerhans cells (HLA-DR and S-100
      double-labeled) as well as other dermal HLA-DR- and S-100-IR dendritic cells, but
      most likely not epidermal Langerhans cells, may be critically involved in the
      development or persistence of prurigo nodularis.

PMID- 9651826
TI  - Increase in the peripheral lymphocyte populations expressing CD54 (ICAM-1) after
      hyperthermic isolated limb perfusion in patients with malignant melanoma: an
      analysis of four cases.
AB  - The lymphocytes isolated from perfused or non-perfused circulations before,
      during, and after hyperthermic isolated limb perfusion (HILP) in the four
      patients with malignant melanoma were analysed for the expression of CD54 (ICAM
      1), CD58 (LFA-3), CD4, CD8, HLA class I and class II in order to investigate the
      mechanism(s) of the activation of such immunocompetent cells as natural killer
      (NK)-cells or T-lymphocytes by HILP. It was thus found that the lymphocyte
      populations expressing CD54 increased significantly 1 day after HILP in the four
      patients examined. The lymphocyte populations expressing CD58 apparently
      increased. It was also found that the NK-cell and T-lymphocyte activities
      increased during or after HILP in the present four cases as observed previously
      in the other melanoma patients. These results indicate that our HILP system may
      augment the immunological activities through the mechanisms of the induction of
      CD54 or CD58 expression in the peripheral lymphocytes of the melanoma patients
      who receive HILP.

PMID- 9651827
TI  - Analysis of antigens targeted by circulating IgG and IgA autoantibodies in 50
      patients with cicatricial pemphigoid.
AB  - In this study we investigated sera from 50 typical cicatricial pemphigoid (CP)
      patients. By indirect immunofluorescence on 1 M NaCl-split human skin sections,
      IgG of 17 sera and IgA of 22 sera reacted with the epidermal side of the split,
      while IgG of two sera reacted with the dermal side. These latter two sera were
      later confirmed to be anti-epiligrin CP. By immunoblotting of epidermal extracts,
      IgG of 14 sera reacted with the 230 kD bullous pemphigoid (BP) antigen (BP230).
      IgG of 15 sera and IgA of 11 sera reacted with the 180 kD BP antigen (BP180).
      Interestingly, a bacterial fusion protein containing the BP180 NC16a domain was
      recognized by IgG of 18 sera but not by IgA of any sera. Fusion proteins
      containing the C-terminal region of BP180 were recognized by IgG of 20 sera, but
      it was detected by IgA of only two sera. Our results suggest that, although CP
      sera show very low titers of autoantibodies, a considerable number of sera
      contain IgG antibodies to BP180 (either NC16a or C-terminal domain), confirming
      previous studies. In addition, we showed that greater numbers of IgA antibodies
      react with BP180, seemingly with different types of epitopes from those for IgG
      antibodies. Because the specificity of IgG antibodies is not very different from
      those in BP, IgA antibodies may play a specific role for the development of
      characteristic clinical features in CP. Future studies should elucidate the
      pathogenic role of the IgA antibodies in CP.

PMID- 9651828
TI  - Increasing incidence of streptococcal impetigo in atopic dermatitis.
AB  - Streptococcal impetigo associated with atopic dermatitis has dramatically
      increased from 1989 to 1994 in outpatients visiting our hospital, totalling 174
      cases. The most frequent causative agents were group A streptococci
      (Streptococcus pyogenes, 70.7%) followed by group G (19.5%) and group B (9.8%).
      Streptococcus was isolated singly in 28.2% of cases and in concomitant with
      Staphylococcus aureus (S. aureus) in 71.8%. Major clinical features of
      streptococcal impetigo, especially caused by group A streptococci, were non
      bullous pustules with thick crusted ceiling. Impetigo caused by group G or B
      streptococci generally formed smaller sized pustules of fewer numbers. Impetigo
      was usually present, associated with severe eczematous lesions. Various degrees
      of fever were noticed in 32.8% (group A, 39.8%; group G, 17.6%; group B, 11.8%)
      during active stages. The lesions on the face often resembled Kaposi's
      varicelliform eruption in any group. Systemic antimicrobial agents were
      administered in 71.3% of cases and the remainder were treated with topical
      antibiotics (oxytetracycline hydrochloride) or disinfectants (povidone-iodine).
      Recurrence occurred within a month in 38.0% of cases treated with topical agents
      only and in 17.7% treated with systemic antimicrobial agents. Antimicrobial
      susceptibility tests and the results of treatment seem to indicate that cephems,
      as well as penicillins, are the first choice of treatment for streptococcal
      impetigo.

PMID- 9651829
TI  - Hair follicle elongation in organ culture of skin from newborn and adult mice.
AB  - By means of skin organ culture, some biological characteristics of hair follicle
      elongation were examined. When skin sections from 6-day-old C3H mice were
      cultured, spontaneous elongation of hair follicles was maintained. Without
      insulin, hair follicle elongation was poorly maintained irrespective of the
      presence of serum at 20%. Insulin could be replaced by IGF-I at 100 ng/ml. During
      in vitro elongation of hair follicles, bromodeoxyuridine was incorporated into
      germinal epithelial cells around dermal papillae. Skin sections from 4-week-old
      C3H mice did not show hair follicle elongation in complete medium. However, when
      0.5 mM minoxidil was added to the medium, concentration dependent thickening and
      elongation of hair follicles was observed. In contrast, in vitro elongation of
      newborn pelage hair follicles was not enhanced by minoxidil. These results
      suggest that this system with the use of skin sections from 4-week-old C3H mice
      would be a potential in vitro model of human androgenic alopecia in which the
      anagen phase is suppressed but the suppression is partially released by
      minoxidil.

PMID- 9651830
TI  - Functional alteration of guanine nucleotide binding proteins (Gs and Gi) in
      psoriatic epidermis.
AB  - Psoriatic involved epidermis has been characterized by a defective beta
      adrenergic adenylate cyclase response. It is also characterized by increased
      cholera toxin- and forskolin-induced cyclic AMP accumulations. Due to the fact
      that receptor signals are transduced to adenylate cyclase through guanine
      nucleotides binding proteins (G-proteins), that affect cholera toxin- and
      forskolin-induced cyclic AMP accumulations, possible alterations of G-proteins of
      psoriatic involved and perilesional uninvolved epidermis by using toxin-catalyzed
      ADP-ribosylation and immunoblot analyses was investigated. Cholera toxin
      catalyzes ADP-ribosylation of stimulatory guanine nucleotides binding protein
      (Gs) in either trimeric (inactive) or monomeric (active) form, while islet
      activating protein (IAP) catalyzes ADP ribosylation of inhibitory guanine
      nucleotide binding protein (Gi) in only trimeric (inactive) form. Results
      indicate that although the psoriatic involved epidermis shows increased cholera
      toxin- and IAP-catalyzed ADP-ribosylations, the amounts of immunoreactive Gs
      alpha or Gi alpha are not significantly altered. The increase in IAP-catalyzed
      ADP-ribosylation indicates increased inactive Gi, explaining the increased
      forskolin-induced cyclic AMP accumulation. The increase in cholera toxin
      catalyzed ADP-ribosylation of Gs explains the increased cholera toxin-induced
      cyclic AMP accumulation in the psoriatic involved epidermis.

PMID- 9651831
TI  - Effects of zinc oxide on the attachment of Staphylococcus aureus strains.
AB  - We examined the attachment of Staphylococcus aureus to plastic tissue-culture
      coverslips after incubation for 24 h. The attachment to coverslips was weaker in
      rabbit plasma with 5% zinc oxide (ZnO) than in the control rabbit plasma without
      ZnO (P < 0.01). Plasma coagulation by S. aureus strains was not detected in
      plasma with 5% ZnO after incubation for 24 h. The membranous structure (an
      immature biofilm) was formed on the coverslips by S. aureus cells in plasma after
      incubation for 24 h. The colony counts of S. aureus cells on the membranous
      structures were lower in plasma with 5% ZnO, plasma with 0.2% hinokitiol, plasma
      with 5% ZnO + 0.2% hinokitiol, plasma with cefdinir at 4 minimum inhibitory
      concentration (MIC) and plasma with levofloxacin at 4 MIC, than in the control
      plasma after incubation for 24 h (P < 0.01). The colonies on the membranous
      structures completely disappeared in the case of plasma with 5% ZnO and 0.2%
      hinokitiol. The colony counts on membranous structures were lower in plasma with
      cefdinir at 4 MIC or levofloxacin at 4 MIC containing 5% ZnO than in plasma with
      cefdinir at 4 MIC or levofloxacin at 4 MIC only, (P < 0.05). The MICs of
      hinokitiol against S. aureus strains peaked at an MIC distribution of 16-32
      micrograms/ml. The peak shifted to below 1 microgram/ml by adding 5% ZnO in agar
      plate method. The results suggest that the attachment of S. aureus cells to the
      coverslips is suppressed in the presence of 5% ZnO and that antistaphylococcal
      activities of cefdinir, levofloxacin and hinokitiol increase in the presence of
      5% ZnO.

PMID- 9651833
TI  - Current aspects of heart valve surgery.

PMID- 9651834
TI  - Aortic root replacement: surgical implications.

PMID- 9651832
TI  - Granulocytes enhance adhesion of peripheral blood mononuclear cells to dermal
      endothelial cells.
AB  - Interactions of all major peripheral blood leukocytes were studied during
      adhesion to human dermal microvascular endothelial cells (HDMEC). Simultaneous
      quantification of distinct leukocytic cell populations was carried in a recently
      established adhesion assay followed by FACS analysis. Adhesion of stimulated
      peripheral blood mononuclear cells (PBMC) was enhanced in the presence of
      granulocytes compared to adhesion of PBMC alone. This effect required direct cell
      cell contact as granulocyte supernatant in the absence of granulocytes failed to
      yield the same extent of PBMC adhesion. Quantification of the common leukocyte
      beta2-integrin subunit (CD18) and the common leukocyte beta1-integrin subunit
      (CD29) as well as blocking with anti-CD18 antibodies revealed no differences
      between PBMC adhering alone or in company of granulocytes to HDMEC. Blocking E
      selectin, however affected 'mixed' (i.e., PBMC in the presence of granulocytes)
      adhesion more profoundly than 'single' adhesion of PBMC. HDMEC subjected to
      'mixed' leukocyte cell adhesion expressed E-selectin at 24 h after cytokine
      stimulation, while HDMEC without contact to leukocytes did no longer express E
      selectin at this time. In conclusion, functionally diverse peripheral blood
      leukocytes can interact in order to enhance cell adhesion without up-regulation
      of leukocytic integrin expression via an E-selectin dependent mechanism.

PMID- 9651835
TI  - Aortic valve replacement with stentless porcine aortic valves: a ten-year
      experience.
AB  - BACKGROUND AND AIMS OF THE STUDY: It has been shown that although stentless
      porcine aortic valves have better hemodynamic features than stented porcine
      valves, their long-term durability remains unknown. This study was undertaken to
      examine the long-term clinical outcome of aortic valve replacement (AVR) with
      stentless porcine aortic valves. METHODS: Between 1987 and 1989, custom-made
      stentless valves were implanted in 29 patients (mean age 58 years), and between
      1991 and 1997, the Toronto SPV was implanted in 213 patients (mean age 63 years).
      In addition to AVR, one-third of the patients had coronary artery bypass. All
      patients were followed up at annual intervals and underwent Doppler
      echocardiography. RESULTS: There were two operative and 11 late deaths (four
      cardiac, seven non-cardiac). The actuarial survival rate was 89 +/- 4% at nine
      years. There were two strokes and seven transient ischemic attacks; freedom from
      thromboembolic complications was 92 +/- 4% at nine years. Two patients developed
      infective endocarditis, one early and one late; freedom from prosthetic valve
      endocarditis was 98 +/- 1% at nine years. Freedom from primary tissue failure was
      85 +/- 8% at nine years. Seven patients required repeat AVR, because of
      endocarditis (two) and aortic insufficiency (five); freedom from repeat AVR was
      82 +/- 8% at nine years. Periodic hemodynamic assessment by echocardiography
      indicated that the mean systolic gradients across the valve decreased during the
      first year of implantation, the valve effective orifice increased, and valve
      competence remained stable. CONCLUSIONS: Stentless porcine aortic valves have
      provided excellent clinical results. These valves may suffer degenerative changes
      and fail at the same rate as stented porcine aortic valves but, because of their
      superior hemodynamic performance, they may enhance patients' survival by allowing
      complete regression of left ventricular hypertrophy and restoration of normal
      ventricular function.

PMID- 9651836
TI  - Mitral valve repair: an odyssey to save the valves!
AB  - The history of mitral valve repair surgery is an interesting odyssey that has
      nearly spanned the century. However, since the mid 1970s, both European and North
      American surgeons have developed and expanded these techniques to where repair of
      myxomatous valves is now expected by most cardiologists and patients.
      Preoperative functional assessment is most important to determine the specific
      needs for repair. Today, transesophageal echocardiography is the standard by
      which cardiologists and surgeons rely for these data. Herein, both methods of
      assessment and techniques for repair are detailed. The multidisciplinary approach
      is emphasized. Risks of surgery are detailed as well as long-term outcomes
      compared with replacement of the mitral valve. Lastly, surgical results from the
      235 patients repair series at the East Carolina University School of Medicine are
      detailed and discussed. This series showed a 1.8% mortality rate for myxomatous
      valve patients, with a very low reoperative rate. This compared with a higher
      mortality rate of 5.6% for the overall group, which emphasizes the increased risk
      associated with an ischemic etiology. The author provides not only an overview
      but also tips to surgeons beginning to repair valves.

PMID- 9651837
TI  - Evaluation of in vivo models for studying calcification behavior of commercially
      available bovine pericardium.
AB  - BACKGROUND AND AIM OF THE STUDY: A common frame of reference is essential when
      attempting to determine if new treatments intended to reduce calcification of
      bioprostheses are superior to existing processes and products. The aim of this
      study was to examine calcification behavior for a commercially available
      pericardial bioprosthesis in subcutaneous and sheep valve models, and to evaluate
      the importance of appropriate control treatments in comparative studies with
      proposed new treatments. METHODS: Samples of bovine pericardium were placed
      subcutaneously under the dorsal skin of weanling rats and juvenile rabbits for 30
      , 60- and 90-day intervals. Samples were either commercially available
      pericardial tissue or tissue processed with phosphate-buffered glutaraldehyde
      alone. Commercially available pericardial valves were also implanted in the
      mitral position in juvenile sheep, with elective sacrifice at 20 weeks. Retrieved
      samples underwent X-ray, histologic and elemental analysis. RESULTS: Commercial
      samples retrieved from the subcutaneous and sheep models showed similar, minimal
      calcification behavior on X-ray and histologic slides, whereas pericardium
      exposed to glutaraldehyde alone demonstrated rapid calcification. CONCLUSIONS:
      The 90-day subcutaneous rabbit model produced patterns of calcification similar
      to those in valves explanted from juvenile sheep after 20 weeks. A statistically
      significant decrease (p < 10(-8)) in calcification was demonstrated for clinical
      pericardium when compared with pericardium exposed to glutaraldehyde alone in the
      subcutaneous model. This suggests that subcutaneous models may be a cost
      effective, time-efficient means of evaluating and comparing various tissue
      treatment methods. The rabbit methodology may provide a more accurate prediction
      of clinical performance, offering a greater degree of sensitivity. These studies
      also indicate that the commercially available process shows minimal calcification
      in the commonly used 30-day weanling rat subcutaneous model, contradicting other
      reported studies that may not accurately represent commercially available
      processes.

PMID- 9651838
TI  - An in vitro bovine pericardial hemocompatibility testing system.
AB  - BACKGROUND AND AIMS OF THE STUDY: Bovine pericardium has been used as a
      biomaterial for heart valves since the late 1960s. Cross-linking agents have been
      applied routinely to reduce host-tissue response, including antigenicity, and to
      improve tissue leaflet durability. Evaluation of improvements in bovine
      pericardial valve leaflet calcification and flexibility require that in vitro
      systems be developed to correlate data with results from in vivo studies. This
      study describes an in vitro test system used to evaluate the effects of two
      surface-modifying treatments on pericardial tissue hemocompatibility. METHODS:
      Non-fixed and glutaraldehyde fixation-processed (GA) bovine pericardial tissues
      were exposed to anticoagulated whole blood for 60 min. Blood was then removed,
      and platelet-poor plasma prepared and frozen at -70 degrees C until analyzed for
      kallikrein activation and release of platelet factor 4 (PF4). Blood-exposed
      tissue samples were analyzed for fibrin (ogen) binding with an anti-fibrinogen
      antibody and for tissue cellular responsiveness (blood cell adherence and
      aggregation) by scanning electron microscopy. RESULTS: Conditions were determined
      for minimum extent of pumping action by the minicam system required to allow for
      solution movement while not tearing or wearing the tissue. A blood-tissue
      exposure time of 60 min provided sufficient first-pass exposure to evaluate the
      acute blood-tissue response. The relative degree of both kallikrein activation
      and PF4 release was greater in the non-fixed tissue but a greater number of
      fibrin(ogen) molecules per cm2 was found on GA-treated tissue. Scanning electron
      microscopy showed a differential cell response of non-fixed tissue compared with
      GA-treated tissue. CONCLUSION: This non-static test system demonstrated great
      promise for use in routine in vitro hemocompatibility testing of blood-contacting
      biological biomaterials.

PMID- 9651839
TI  - Comparative assessment of hepatic Glisson's capsule and bovine pericardium in
      heart valve bioprostheses.
AB  - BACKGROUND AND AIM OF THE STUDY: The optimal material for heart valve
      bioprostheses remains disputable. This investigation was initiated to compare the
      properties of hepatic Glisson's capsule, clinical experience of which in
      cardiovascular surgery is minimal, with those of bovine pericardium. METHODS:
      Hepatic Glisson's capsule was harvested from bull calves and used to create
      composite pulmonary arterial monocusp grafts and bioprostheses. Comparison of the
      strength and elastic properties of Glisson's capsule and bovine pericardium, as
      well as the hydrodynamic characteristics of valves made from these materials, was
      performed. Late results of operations using these materials were estimated
      echocardiographically. RESULTS: Although Glisson's capsule tissue is thinner than
      the bovine pericardium, its elasticity modulus is greater. However, the
      hydrodynamic characteristics of heart valves made from either tissue are similar.
      Moreover, valves made from Glisson's capsule have a lower systolic pressure
      gradient on the prosthesis and a higher effective orifice area. Composite
      pulmonary arterial xenopericardial grafts with a monocusp of Glisson's capsule
      were used in 30 patients during tetralogy of Fallot repair. Glisson's capsule was
      also used for tricuspid valve reconstruction and as a bioprosthesis in six
      patients with Ebstein's anomaly. At 1-2 years after surgery, the Glisson's
      capsule tissue remained thin and flexible, with no calcification. CONCLUSIONS:
      Although the hydrodynamic properties of hepatic Glisson's capsule and the bovine
      pericardium are similar, the capsule tissue is thinner and has a greater
      elasticity modulos. Thus, Glisson's capsule may be used for bioprosthesis
      construction both independently and in combination with bovine pericardium.

PMID- 9651840
TI  - Long-term results with the Sorin Pericarbon valve in the aortic position: a
      multicenter study.
AB  - BACKGROUND AND AIM OF THE STUDY: A multicenter study was designed to evaluate the
      Pericarbon pericardial bioprosthesis for up 10 years after implantation in the
      aortic position. METHODS: Between January 1986 and November 1996, 321 patients
      (mean age 75.8 +/- 7.3 years) received 325 Pericarbon pericardial valves in the
      aortic position. Four patients underwent redo surgery and each received a second
      Pericarbon prosthesis. Associated cardiac procedures in 80 patients were mainly
      coronary bypass (n = 66). Follow up extended up to 10 years (cumulative follow up
      of 931.0 patient-years; mean follow up 3.1 +/- 2.2 years). RESULTS: There were 19
      late deaths, with seven valve-related. Twelve patients suffered an embolic
      complication (transient cerebral attack in four, peripheral in six and induction
      of a myocardial infarction in two). Of these complications, five occurred within
      30 days of surgery and seven beyond the first year. Ten patients were reoperated
      on, six for primary tissue failure, two for prosthetic endocarditis and two for
      paraprosthetic leak. Primary failure was due in all cases to leaflet
      mineralization. No primary tear of the leaflet was reported. Actuarial freedom
      after 10 years from primary tissue failure was 83.9 +/- 7.4% and from major
      embolic events 97.6 +/- 1.0%. Freedom from valve-related mortality at 10 years
      was 92.1 +/- 4.9%. CONCLUSIONS: These results indicate that, over a period of up
      to 10 years, the Pericarbon pericardial bioprosthesis compares favorably with
      other replacement valves.

PMID- 9651841
TI  - Detoxified glutaraldehyde cross-linked pericardium: tissue preservation and
      mineralization mitigation in a subcutaneous rat model.
AB  - BACKGROUND AND AIM OF THE STUDY: Glutaraldehyde is considered a promoter of
      calcification by the action of toxic aldehyde group residuals from cross-linking.
      Post-fixation treatment with homocysteic acid (HA), besides bonding aldehyde
      groups and neutralizing toxicity, should enhance biocompatibility due to the
      strongly electronegative sulfonic group. The aim of this investigation was to
      evaluate HA efficacy on tissue preservation and dystrophic calcification
      mitigation in glutaraldehyde cross-linked bovine pericardium (BP) using a
      subcutaneous rat model. METHODS: Four samples of BP, two with glutaraldehyde-HA
      and two with glutaraldehyde treatment, were implanted in each of 24 male Sprague
      Dawley rats. Three rats were killed at 14 days, eight at 28 days, eight at 56
      days and five at 84 days. Unimplanted glutaraldehyde-HA- and glutaraldehyde
      treated samples served as controls. All samples were studied by gross
      examination, mammography, light transmission and scanning electron microscopy,
      and atomic absorption spectroscopy. The nature of mineralization was investigated
      by coupling techniques of scanning electron microscopy, electron microprobe
      analysis and X-ray powder diffraction. RESULTS: No histological and
      ultrastructural differences were found between glutaraldehyde-HA- and
      glutaraldehyde-treated BP, whether implanted or unimplanted. In both groups,
      calcification progressed with time, but significantly less after glutaraldehyde
      HA treatment than after glutaraldehyde alone and at all time intervals (14.63 +/-
      21.34 versus 43.17 +/- 15.99 at 28 days, p = 0.003; 56.42 +/- 40.20 versus 90.59
      +/- 32.90 at 56 days, p = 0.008; 91.68 +/- 67.68 versus 156.23 +/- 17.85 at 84
      days, p = 0.01). Differences were evident by mammography and histology (von Kossa
      stain). Electron microprobe analysis in both groups showed the composition of
      calcified nuclei to be calcium phosphate, stoichiometrically close to apatite
      (Ca5(PO4)3(OH)). The occurrence of crystallized apatite was supported by X-ray
      powder diffraction findings, the amount of crystallized apatite being higher in
      glutaraldehyde-treated samples. CONCLUSIONS: Post-fixation treatment with HA
      preserves BP structural properties and significantly mitigates mineralization of
      long-term subcutaneous implants.

PMID- 9651842
TI  - Twelve-year experience with Carpentier-Edwards PERIMOUNT pericardial valve in the
      mitral position: a multicenter study.
AB  - BACKGROUND AND AIMS OF THE STUDY: The study aim was to assess the durability of
      the Carpentier-Edwards PERIMOUNT pericardial bioprosthesis in the mitral
      position. METHODS: This seven-center retrospective clinical study involved the
      follow up of 333 patients who underwent isolated mitral valve replacement and 102
      patients who underwent double (mitral and aortic) valve replacement with the
      PERIMOUNT pericardial valve between 1984 and 1989. Mean patient age at implant
      was 60.7 +/- 11.6 years; 41.1% were males. The most common etiology was rheumatic
      heart disease (53.9%) and the most common mechanism mitral insufficiency. All
      patients but six were followed for an average of 7.2 +/- 3.6 years after surgery;
      total follow up was 3071.7 patient-years (pt-yr). RESULTS: The total operative
      mortality rate was 7.6%; this included a valve-related mortality rate of 0.2%.
      The late mortality rate was 5.2% per pt-yr, of which 1.4% per pt-yr was
      considered valve-related. At 11 years, the overall actuarial survival rate was
      53.3 +/- 2.8%, and actuarial freedom from valve-related death 83.9 +/- 2.6%. At
      follow up, 80% of patients were in NYHA class I or II, and 74% showed
      improvement. Twenty-eight incidences of deterioration requiring explant were
      observed. At 11 years the actuarial freedom from explant due to structural
      failure was 84.9 +/- 3.1%. Rates of structural failure decreased with age: the
      actuarial freedom from explant due to structural failure was 78.1 +/- 4.8% for
      patients aged < or = 60 years, 89.4 +/- 4.4% for those aged 61-70 years, and 100%
      for those aged over 71 years. CONCLUSION: The Carpentier-Edwards PERIMOUNT
      pericardial bioprosthesis is a reliable choice when a tissue valve is required,
      especially in patients over 60 years of age.

PMID- 9651843
TI  - Enlargement of the aortic annulus with glutaraldehyde-fixed bovine pericardium
      during aortic valve replacement.
AB  - BACKGROUND AND AIMS OF THE STUDY: Aortic valve replacement in patients with a
      small aortic annulus may represent a surgical challenge. We have evaluated a
      simplified technique to enlarge the aortic annulus which consists of extending
      the aortotomy incision to divide the commissure between the left and non-coronary
      cusps into the interleaflet triangle without opening the left atrium. METHODS:
      This technique was used in 16 patients (15 women, one man; mean age 66 +/- 9
      years) who underwent aortic valve replacement between August 1994 and February
      1996. Aortic stenosis was the predominant valvular lesion. A mechanical
      prosthesis was implanted in 13 patients (81%) (21 mm in six, 23 mm in seven)
      while three received a bioprosthesis (21 mm in one, 23 mm in two). In all
      patients it was possible to insert a prosthesis at least one size larger than the
      original aortic annulus diameter. RESULTS: There were no operative deaths and no
      late deaths. Mean follow up was 20 +/- 6 months (range: 12 to 30 months).
      Echocardiographic controls at 12 months postoperatively showed no evidence of
      periprosthetic leaks or mitral regurgitation. Comparison with preoperative data
      showed no significant variations of mean aortic diameter at the sinus level (30.7
      +/- 2.2 mm versus 31.3 +/- 2.6 mm) or at the sinotubular junction (33.6 +/- 2.7
      mm versus 34.3 +/- 2.9 mm) (p = NS). Significant reduction of left ventricular
      mass was observed (314 +/- 57 g versus 260 +/- 45 g; p < 0.001). CONCLUSIONS:
      This technique is simple, reproducible and effective in allowing adequate
      enlargement of the aortic annulus and provides excellent clinical and hemodynamic
      results. Glutaraldehyde-fixed bovine pericardium used as a patch material showed
      no tendency to aneurysmal dilatation with progression of time at a maximum follow
      up of 30 months.

PMID- 9651845
TI  - Better understanding of the pathogenesis of prosthetic valve endocarditis--recent
      perspectives for prevention strategies.

PMID- 9651844
TI  - Aortic reconstruction with crimped bovine pericardial conduits.
AB  - BACKGROUND AND AIM OF THE STUDY: A bovine pericardial conduit processed in
      glutaraldehyde was designed, incorporating the principle of crimping used for
      synthetic vascular prostheses. The crimping process did not affect the integrity
      of collagen fibers and tissue structure. This conduit, designed for aortic
      reconstruction, is available in different sizes, with or without a biological
      valve. METHODS: Between October 1989 and May 1997, 40 patients with aortic
      dissection, aortic aneurysm, aortic coarctation or aortoiliac occlusive disease
      underwent aortic reconstruction using this vascular substitute. Procedures
      included total reconstruction of the ascending aorta and aortic valve with
      reimplantation of coronary arteries (nine patients), single ascending thoracic
      aorta (six), descending thoracic aorta (two), aortic arch (one) and
      thoracoabdominal aorta (one); the abdominal aorta was reconstructed in 21 cases,
      including those undergoing aortoiliac or aortofemoral bypass. RESULTS: The
      hospital mortality rate was 20% (eight patients); causes of deaths were low
      cardiac output, recurrence of aortic dissection, multiple organ failure and
      bleeding. Mean follow up was 3.6 years; total follow up was 114 patient-years.
      Late conduit-related complications occurred in four patients, including a limb
      obstruction in one patient subjected to aortofemoral bypass and infection of
      three resulting in pseudoaneurysm (incidence of 3.5 +/- 1.8% per patient-year).
      All underwent reoperation. There were four late deaths due to sudden death,
      coronary artery disease, pneumonia and metabolic complications of diabetes and
      renal failure (incidence of 3.5 +/- 1.8% per patient year). The eight-year
      actuarial survival rate was 63.7 +/- 11.6%, including hospital mortality, and the
      eight-year actuarial freedom from conduit failure due to primary tissue
      structural degeneration was 100%. CONCLUSIONS: The crimping design provides a
      circular tube which makes construction of the anastomosis easier, retains its
      shape with bending, and avoids kinking. The material is very soft, easy to handle
      and suture, coapts nicely to suture lines resulting in a hemostatic anastomosis.
      The eight-year follow up demonstrated a satisfactory performance without report
      of fibrosis, calcification or aneurysmal dilation.

PMID- 9651846
TI  - Strategies for prophylaxis against prosthetic valve endocarditis: a review
      article.
AB  - Prosthetic valve endocarditis (PVE) is an important cause of the morbidity and
      mortality associated with heart valve replacement surgery. Once established, it
      carries a mortality rate that may be as high as 70%. The only treatment for
      established PVE is rigorous intravenous antimicrobial therapy, although this has
      extremely limited success. The majority of cases require surgical removal and
      replacement of the infected prosthesis. At present, the only means of preventing
      PVE are scrupulous asepsis and prophylactic perioperative antibiotic therapy. If
      another strategy could be developed that is effective and safe, the incidence of
      this disastrous complication of valve replacement would be reduced. Such
      strategies have been extensively investigated from a variety of different
      perspectives for several years. The understanding of biofilms appears to be
      pivotal to the development of a successful approach. The historic background to
      the prevention of PVE, and the current state of research into this area are
      discussed.

PMID- 9651847
TI  - Histopathologic comparison of a pulmonary autograft and pulmonary homograft in a
      patient 17 months after a Ross procedure: an autopsy study.
AB  - BACKGROUND AND AIM OF THE STUDY: The Ross operation has become very popular
      during the last decade. However little is known about the cellular behaviour of a
      normally functioning pulmonary autograft. METHODS: This case report deals with a
      14-year-old female who died from a non-valve-related cause 17 months after a Ross
      Konno operation using a cryop-reserved viable pulmonary homograft for the right
      outflow tract. Comparison is made between the homologous and autologous pulmonary
      valves by macroscopic description, histology and immunohistochemistry. RESULTS:
      The autograft kept its cellular population-except for the dendritic cells which
      have disappeared, and developed a jet lesion on the ventricular aspect of one
      cusp as a likely adaptation to a transvalvular gradient. The homograft was
      extensively devitalized, its cusps being partially covered with a fibrous sheath
      of recipient origin; few inflammatory cells, consisting of macrophages and rare T
      lymphocytes were present. CONCLUSIONS: The most puzzling observation, which needs
      confirmation, is the selective disappearance of the dendritic cells from the
      viable autograft. It is disappointing that a viable cryopreserved homograft valve
      has devitalized in the midterm. This phenomenon seems to result from a clinically
      silent immune reactions.

PMID- 9651848
TI  - Clinical experience with the Carpentier-Edwards supra-annular porcine
      bioprosthesis implanted in the aortic position.
AB  - BACKGROUND AND AIMS OF THE STUDY: Between 1st January 1988 and 30th June 1996, a
      total of 165 patients (115 males, 50 females; mean age 66.8 years) underwent
      isolated aortic valve replacement with Carpentier-Edwards supra-annular porcine
      bioprostheses in our unit. Our clinical experience with this device is reported.
      METHODS: In this retrospective study, mortality and complications observed in
      these patients were analyzed. Complications appearing with a non-biased time
      course were expressed by means of linearized rates. Actuarial analysis was
      performed using the Kaplan-Meier method. RESULTS: Cumulative follow up was 551.2
      patient-years, with a mean follow up of 3.5 years per patient. The hospital
      mortality rate was 6.7%. Linearized rates (events per 100 patient-years) and
      actuarial probabilities of freedom from the different complications at 8.5 years
      follow up, respectively, were: late mortality, 4.5 and 58.6%; valve-related
      mortality, 1.1 and 82.6%; thromboembolism, 1.3 and 92.7%; prosthetic
      endocarditis, 0.5 and 97.4%; non-structural dysfunction, 0.5 and 94.7%;
      structural deterioration, 0.5 and 91.6%; reoperation, 0.5 and 94.2%. Actuarial
      freedom from any valve-related mortality or morbidity at 8.5 years was estimated
      at 66.3%. CONCLUSIONS: The Carpentier-Edwards supra-annular bioprosthesis, when
      implanted in the aortic position, presents a low rate of valve-related
      complications at this length of follow up. However, the limited life expectancy
      of our patients undergoing aortic valve replacement with bioprostheses (usually
      elderly subjects) may overshadow the potential good performance of this device.

PMID- 9651849
TI  - In vitro effects of anticalcification treatment on the calcium uptake of
      bioprosthetic materials.
AB  - BACKGROUND AND AIM OF THE STUDY: The frequent need for re-replacement of tissue
      valves due to calcification remains their major disadvantage compared with
      mechanical implants. A variety of anticalcification treatments has been proposed
      but none has proved to prevent calcific degeneration. The study aim was to
      evaluate, in vitro, the time course of calcium uptake of procine and bovine
      biomaterials and the efficacy of anticalcification treatments. METHODS: Samples
      of glutaraldehyde-tanned biomaterials with (Carpentier-Edwards, Medtronic Intact,
      Hancock II, MZGTB) or without anticalcification treatment (Mitroflow) were
      incubated with culture medium containing physiological calcium levels. Specimens
      were then analyzed at two, four or eight weeks for their calcium content (mg/g
      wet weight). RESULTS: All specimens calcified over time, though the time courses
      for each were significantly different. Mitroflow and Intact valves accumulated
      high calcium levels rapidly during the first two weeks, with small further
      increases thereafter. Anticalcification treatment reduced calcium uptake of
      Carpentier-Edwards material during the first two weeks of incubation, but the
      material gradually attained comparable calcium levels at eight weeks. Hancock
      valves and the self-customized MZGTB valve showed the lowest calcium levels over
      the test period. CONCLUSIONS: This in vitro study documented major differences in
      calcium uptake of different biomaterials. Some anticalcification treatments
      render the material temporarily less susceptible to calcium binding but none can
      prevent calcification. In vitro testing has proved to be a valuable instrument
      for evaluating anticalcification treatments, but should be combined with
      evaluation of bioprosthesis surface interaction with circulating blood.

PMID- 9651850
TI  - Prevalence of microbubbles associated with mechanical prosthetic cardiac valves:
      a prospective transesophageal echocardiography study.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to identify the prevalence of
      microbubbles in different types of mechanical cardiac valve and, if feasible, to
      associate microbubbles with various clinical conditions, including thrombotic
      occlusion of the valves. METHODS: A total of 153 mechanical prosthetic valves
      were studied (58 aortic, 95 mitral) in 140 patients, prospectively. All valves
      were functioning normally. In addition, eight mitral prosthetic valves were
      selected without microbubbles and with an obstructive valvular thrombosis that
      had undergone successful thrombolysis (group 1); a further eight patients with
      unsuccessful thrombolysis (group 2) were studied by transesophageal
      echocardiography before and after thrombolytic therapy. RESULTS: Microbubbles
      were detected in 75% (114/153) of prosthetic valves, 99% (88/89) of bileaflet
      valves, and 45% (29/64) of monoleaflet valves (p < 0.0001). Only 14% (4/28) of
      Sorin monoleaflet valves were associated with microbubbles, which is
      distinctively less than other valves (p < 0.001 for each); 71% and 77% of aortic
      and mitral prosthetic valves, respectively, were associated with microbubbles (p
      = NS). Prosthetic valves with an obstructive thrombosis and no microbubbles in
      group 1 showed new appearance of microbubbles in 88% (7/8) of cases after
      successful thrombolysis. Absence of microbubbles in group 2 persisted in all
      eight patients at the second examination. CONCLUSIONS: Microbubbles were detected
      in a greater proportion of patients than reported previously and were found to be
      associated more with bileaflet prosthetic heart valves than with monoleaflet
      valves. Sorin monoleaflet valves were associated with microbubbles dramatically
      less than all other valves. The new appearance of microbubbles after thrombolytic
      therapy of mechanical prosthetic heart valves with an obstructive thrombosis may
      indicate successful thrombolysis.

PMID- 9651851
TI  - The hemodynamic effects of mechanical prosthetic valve type and orientation on
      fluid mechanical energy loss and pressure drop in in vitro models of ventricular
      hypertrophy.
AB  - BACKGROUND AND AIMS OF THE STUDY: When choosing a prosthetic replacement for a
      natural heart valve, one objective should be to minimize the workload placed on
      the heart. This workload can be raised by fluid mechanical energy losses imposed
      by the valve. For a patient with left ventricular hypertrophy, certain aortic
      valve types and orientations could be hemodynamically superior to others.
      METHODS: This study used a control volume analysis to investigate the effects of
      prosthetic mechanical aortic valve type and orientation on fluid mechanical
      energy losses in four in vitro models of the left ventricular outflow/aortic
      inflow tract in various degrees of hypertrophy. Flow visualization studies were
      performed to qualitatively validate this analysis. The two most commonly used
      mechanical valve designs were studied: the St. Jude Medical (SJM) bileaflet valve
      and the Medtronic Hall (MH) tilting disk valve. Experiments were performed in
      pulsatile flow at a constant heart rate of 60 beats per min for five valve
      type/orientation combinations. The stroke volume was varied between 40 and 120 ml
      in five increments for each model and valve/orientation studied. RESULTS: Valve
      type and orientation was found to have a significant effect on energy losses in
      these models (p < 0.05). Valve/orientation combinations with leaflets or disks
      approximately parallel to the proximal flow direction created lower energy losses
      than others. The MH valve in the 180 degrees orientation caused significantly
      less energy losses and pressure drops (orifice and recovered) than any of the SJM
      valve/orientations studied (p < 0.05). The SJM and MH valves in the 0 degree
      orientation were responsible for significantly more energy loss than other
      valve/orientations studied (p < 0.05). An aortic inflow tract model with severe
      (45 degrees) curvature created significantly more energy loss (p < 0.05) than
      those with less curvature (15 and 30 degrees). However, the insertion of an
      obstruction simulating a hypertrophic tissue outgrowth caused much more energy
      loss than increasing the severity of outflow tract curvature from 15 to 45
      degrees. Both orifice pressure drop and recovered pressure drop had excellent
      linear correlations with energy losses found in these models. CONCLUSIONS: These
      results imply that: (i) prosthetic valve type and orientation should be
      considered when replacing the aortic valve of a hypertropic patient; (ii) removal
      of obstructions within the aortic inflow tract will decrease ventricular
      workload; and (iii) the Doppler-estimated pressure gradients commonly use by
      cardiologists to assess the performance of a prosthetic valve, correlate very
      well with left ventricular energy loss and work load.

PMID- 9651852
TI  - Hypertrophic cardiomyopathy in pregnancy. The use of two-dimensional and Doppler
      echocardiography during labor and delivery: a case report.
AB  - Hypertrophic cardiomyopathy (HCM) in pregnancy can result in a high incidence of
      maternal complications. Although echocardiography is frequently performed in
      pregnant women with HCM in order to confirm their hemodynamic classification,
      this modality has not been applied during labor and delivery in these patients.
      This case report documents the application of two-dimensional and Doppler
      echocardiography during labor and delivery in a 35-year-old woman with HCM.

PMID- 9651853
TI  - Trying to control MRSA causes more problems than it solves.
AB  - Despite occasional reports of local success, the steadily increasing prevalence
      of strains of Staphylococcus aureus resistant to methicillin (MRSA) shows that
      attempts to limit their spread do not work. In this commentary we suggest that
      efforts to control the spread of methicillin-resistance are counterproductive,
      and that energies should instead be directed towards the control of outbreaks of
      disease and preventing the emergence of antibiotic resistance.

PMID- 9651854
TI  - The epidemiology and prevention of invasive aspergillosis.
AB  - Over the past two decades, the incidence of invasive aspergillosis (IA) has risen
      inexorably. This is almost certainly the consequence of the more widespread use
      of aggressive cancer chemotherapy regimens, the expansion of organ transplant
      programmes and the advent of the acquired immunodeficiency syndrome (AIDS)
      epidemic. Despite the development of new approaches to therapy, IA still remains
      a life-threatening infection in immunocompromised patients and is the most
      important cause of fungal death in cancer patients. It is clear that the
      prevention of severe fungal infection by the use of effective infection control
      measure should be the priority of the teams involved in managing at-risk
      patients. The evidence from clinical and molecular epidemiological studies is
      reviewed and current thinking on sources and routes of transmission of the
      organism are discussed. Our increasing understanding of these has led to the
      development of a variety of environmental and general strategies for the
      prevention of IA. It is anticipated that these, coupled with the use of
      prophylactic antifungal agents active against Aspergillus spp., will have a
      significant impact upon the morbidity and mortality associated with this
      infection.

PMID- 9651855
TI  - An outbreak of multi-drug-resistant tuberculosis in a London teaching hospital.
AB  - We describe the epidemiology and control of a hospital outbreak of multi-drug
      resistant tuberculosis (MDR-TB). A human immunodeficiency virus (HIV)-negative
      patient with drug-sensitive tuberculosis developed MDR-TB during a period of
      unsupervised therapy. She was admitted to an isolation room in a ward with HIV
      positive patients, but the room, unbeknown to hospital staff, was at positive
      pressure relative to the main ward. Seven HIV-positive contacts developed MDR-TB.
      The diagnosis in the second patient was delayed, partly because acid-fast bacilli
      in his sputum were assumed to be Mycobacterium avium-intracellulare. All the
      available Mycobacterium tuberculosis isolates were indistinguishable by molecular
      typing. Nearly 1400 staff and patient contacts were offered screening, but the
      screening programme detected only one of the cases. Despite therapy, the index
      patient and two of the contacts died. HIV-positive patients are more likely than
      others to develop tuberculosis after exposure, and the disease may progress more
      rapidly. In these patients the possibility that acid-fast bacilli may represent
      M. tuberculosis must always be considered. Patients with tuberculosis (suspected
      or proven) should not be nursed in the same wards as immunosuppressed patients,
      and should be isolated. MDR-TB cases must be isolated in negative-pressure rooms.
      Hospital side-rooms may be positive-pressure as a fire safety measure; infection
      control teams must be aware of the airflows in all isolation rooms, and must be
      consulted during the design of hospital buildings. Good communication between
      infection control teams and clinicians is important, and all medical and nursing
      staff must be aware of the principles of management of patients with proven or
      suspected tuberculosis and MDR-TB.

PMID- 9651856
TI  - Comparison of wound scoring methods for use in audit.
AB  - Accurate information on the prevalence of surgical wound infection is difficult
      to obtain; outpatient follow-up is often inadequate. For two months in 1993 and
      again in 1995, surgical wounds throughout one hospital were examined by the same
      observer with the intention of comparing different methods for assessing wound
      infection. Two standard definitions [Centers for Disease Control (CDC), USA and
      National Prevalence Survey (NPS), UK] were compared with ASEPSIS and the
      Southampton method. In 1993, 325 wounds in 230 patients were examined with follow
      up of 203 (88%) patients. In 1995, 559 wounds were surveyed in 375 patients with
      follow-up in 364 (97%). Patient groups in the two years were similar. ASEPSIS
      identified 92 (13%) wounds as having scored over 20 points indicating infection,
      and another 16.5% having disturbance of healing. There was no significant
      difference between the two surveys. The two scoring methods were more sensitive
      than the standard definitions but CDC and NPS did not differ significantly from
      each other. Between 44 and 47% of clean wounds identified as infected by standard
      definitions were classed as disturbance of healing by ASEPSIS. All methods were
      labour-intensive and to implement any one of them on a regular basis would
      require a full-time investigator. The first surveillance program with feedback of
      results to the surgeons did not significantly affect the rates two years later.

PMID- 9651857
TI  - Ventilation grilles as a potential source of methicillin-resistant Staphylococcus
      aureus causing an outbreak in an orthopaedic ward at a district general hospital.
AB  - The spread of methicillin-resistant Staphylococcus aureus (MRSA) in a hospital is
      thought to be mainly by direct contact. Environmental sources such as exhaust
      ducting systems have been increasingly recognized as a source for MRSA outbreaks
      in intensive therapy units. We describe an outbreak of MRSA related to
      ventilation grilles in an orthopaedic ward. Six patients and one nurse were
      involved in an outbreak with EMRSA-15 during March 1996. The index case was
      transferred from a large university hospital in Leeds. One of the patients had
      shared the same bay with the index case. The rest of the patients were in another
      bay of the same ward and had no direct contact with the index patient. An
      environmental source was suspected and the ventilation grilles in boys 1 and 2
      were found to be harbouring EMRSA-15. The ventilation system at that time was
      working on an intermittent cycle from 4 p.m.-8 a.m. Daily shut-down of the system
      temporarily created a negative pressure, sucking air in from the ward environment
      into the ventilation system and probably contaminating the outlet grilles. It is
      likely that contaminated air was blown back into the ward when the ventilation
      system was started. The system was thoroughly cleaned, appropriate infection
      control measures were instituted and the ventilation system was put back on a
      continuous running cycle and the outbreak terminated. Six months after the
      outbreak no isolates of EMRSA-15 had been made on the ward.

PMID- 9651858
TI  - An outbreak of an unusual strain of Serratia marcescens in two Dublin hospitals.
AB  - We describe a serious outbreak of infection caused by a strain of Serratia
      marcescens in two Dublin hospitals which occurred over an 11 week period and
      affected a total of 15 patients. A contaminated bed-pan macerator in the
      Intensive Care Unit of one hospital was identified as the possible source of
      infection and spread of the organism probably occurred via hand transmission by
      hospital personnel and via patient transfer to a second hospital. All isolates of
      S. marcescens involved in the outbreak had the same antimicrobial susceptibility
      pattern, with reduced susceptibility to gentamicin, cefotaxime and ciprofloxacin.
      Epidemiological typing revealed that the strains of S. marcescens isolated in the
      outbreak were of an uncommon serotype, O21:K14, and using pulsed-field gel
      electrophoresis, XbaI DNA macrorestriction profiles clustered at 90% similarity.
      The DNA patterns of the outbreak strain were also highly similar to S. marcescens
      isolates of the same serotype recovered from a separate Dublin hospital during
      the same time period as the outbreak described here. In addition, the isolates
      clustered at 82% similarity with strains of the same serotype from a
      retrospective collection of S. marcescens isolates from various hospitals in the
      Dublin area, indicating that these may be genetic variants of the same strain.
      Although the outbreak was brought under control following implementation of
      infection control measures, a significant number of similar O:21 isolates of S.
      marcescens have since been identified in four Dublin hospitals. These results
      suggest the unique spread of a single strain of S. marcescens in Dublin
      hospitals.

PMID- 9651859
TI  - Incidence of nosocomial pneumonia in a medical intensive care unit and general
      medical ward patients in a public hospital in Bombay, India.
AB  - We prospectively studied the incidence of hospital-acquired pneumonia in 1886
      consecutive admissions to an 1800 bed hospital in Bombay; 991 of them to general
      medical wards and 895 to a 17-bed medical intensive care unit (ICU). The average
      bed occupancy in the general wards was 56 patients in a ward with 40 beds.
      Staffing in the general ward was two nurses for 56 patients, and in the ICU three
      nurses for 17 beds. One hundred and sixty-eight patients developed nosocomial
      pneumonia: 18 (1.8%) in general wards and 150 (16.7%) in the ICU. Common isolates
      included Pseudomonas spp (44%) and Klebsiella spp (34%). The most frequently used
      antibiotics were cefotaxime (34%), amikacin (25%), gentamicin (23%) and ofloxacin
      (13%). Crude mortality in general ward patients was 88.9 vs 14.6% in patients
      without pneumonia. The corresponding figures for ICU patients were 67.4 vs 37.1%;
      40% of the crude mortality in ICU patients with pneumonia was attributable to the
      infection. Infected patients stayed an additional 5.8 days in the ICU and 6.7
      days in the general ward. Costs of additional stay and antibiotics accounted for
      18.6% of the ICU budget. The incidence of nosocomial pneumonia was lower than
      expected, despite occupancy exceeding bed capacity, low nurse:patient ratios, and
      extensive reuse of disposable respiratory therapy equipment. Nevertheless,
      nosocomial pneumonia imposes a significant financial burden on the already scarce
      resources available for intensive care in developing countries like India.

PMID- 9651860
TI  - Detection of persistent vegetative bacteria and amplified viral nucleic acid from
      in-use testing of gastrointestinal endoscopes.
AB  - Hospital-acquired infection attributed to inadequate decontamination of
      gastrointestinal endoscopes prompted an in use evaluation of recommended
      procedures. Specimens were obtained from the internal channels of 123 endoscopes
      before, during and after decontamination by flushing with saline and brushing
      with a sterile brush, and examined for vegetative bacteria by broth and plate
      culture. Four endoscopy units were tested; the chemical disinfectants used were:
      2% glutaraldehyde in Centres 1 and 2 (automated) and Centre 3 (manual); peracetic
      acid in Centre 4 (automated). Samples from patients in Centre 1 with known
      chronic hepatitis B virus (HBV), hepatitis C virus (HCV) and human
      immunodeficiency virus (HIV-1) infection were also examined for viral nucleic
      acid by ultracentrifugation, nucleic acid extraction, reverse transcription (for
      RNA) and polymerase chain reaction (PCR). No persistent vegetative bacteria were
      found following standard manual cleaning and disinfection for 20 min in 2%
      glutaraldehyde in Centres 2 and 3 (N = 37). At Centre 1, while plate culture
      yielded no growth, 34% of samples (10/29) grew vegetative bacteria in broth
      culture after cleaning and disinfection for 20 min in 2% glutaraldehyde.
      Investigation revealed an error in manual cleaning; no bacteria were detected in
      37 samples taken after this was corrected. At Centre 4, despite the use of
      peracetic acid as a sterilant, three out of 20 (15%) of post decontamination
      samples grew bacteria; one contained persistent bacteria. HBV and HCV PCR
      analysis detected viral nucleic acid in three out of four and four out of six
      samples from viraemic patients undergoing endoscopy in Centre 1 during the period
      of improper manual washing. After proper cleaning was instituted, samples from
      nine out of nine HCV viraemic patients were negative. HIV RNA was detected in
      five of 14 samples taken from endoscopes after use on HIV positive patients but
      all post decontamination samples were negative. Detection of bacteria in washes
      from endoscope channels is a useful warning of a breakdown in decontamination
      practice. Inadequate brushing of internal channels may result in persistent HCV
      and HBV viral nucleic acid, the significance of which is not clear. These results
      reinforce the importance of adequate manual cleaning of endoscopes before
      chemical disinfection.

PMID- 9651861
TI  - Screening medical students for MRSA.

PMID- 9651862
TI  - Computerized detection of re-admission of patients with MRSA.

PMID- 9651863
TI  - Effects of poly(vinylpyrrolidone) and ethylcellulose on alginate microspheres
      prepared by emulsification.
AB  - Calcium alginate microspheres were prepared by an emulsification process. The
      effects of two co-polymers, namely poly(vinylpyrrolidone) and ethylcellulose, on
      the properties of the microspheres were studied. Microspheres prepared with and
      without poly(vinylpyrrolidone) were spherical and discrete. The microspheres
      containing poly(vinylpyrrolidone) exhibited a better flow property but the drug
      content was lower and the drug release rate higher. The method of incorporating
      poly(vinylpyrrolidone) was found to (significantly) affect the size distribution
      and drug content of the microspheres. Ethylcellulose produced marked aggregation
      of the microspheres which also showed a lower drug content, but a slower drug
      release. The retardation in drug release was attributed to the formation of
      aggregated microspheres with a less permeable matrix. The addition of triethyl
      citrate, which is a water-soluble plasticizer, was found to increase the rate of
      drug release while the use of a higher viscosity grade of ethylcellulose produced
      the opposite effect. Ethylcellulose improved the flowability of the microspheres
      to a greater extent than poly(vinylpyrrolidone).

PMID- 9651864
TI  - Changing the pH of the external aqueous phase may modulate protein entrapment and
      delivery from poly(lactide-co-glycolide) microspheres prepared by a w/o/w solvent
      evaporation method.
AB  - The milk model protein, beta lactoglobulin (BLG), was encapsulated into
      microspheres prepared by a multiple emulsion/solvent evaporation method. The
      effect of the pH of the outer aqueous phase on protein encapsulation and release
      as well as on microsphere morphology has been investigated. At all tested pH
      values, the encapsulation efficiency was shown to decrease with increasing the
      initial amount of BLG. This was correlated with the reduced stability of the
      primary emulsion as the initial BLG increased. In addition, reducing the
      solubility of BLG in the external aqueous phase by decreasing the pH to the
      isoelectric point of BLG (pI 5.2) resulted in an improved protein encapsulation.
      Moreover, it was shown that combining pH modification and optimal stability of
      the first emulsion yielded microspheres with a high encapsulation efficiency.
      However, release kinetic studies revealed that a significant burst release was
      observed with microspheres loaded with large amounts of BLG, especially when
      prepared in a medium at pH 5.2. This burst effect was attributed to morphology
      changes in the microsphere surface which was characterized by the presence of
      pores or channels able to accelerate the release of BLG. These pores were assumed
      to result from the presence of large amounts of protein molecules on the
      microsphere surface, that aggregate during microsphere formation at pH 5.2.
      Indeed, single adsorption experiments have shown that BLG had a higher affinity
      for the particle surface when the pH was close to the pI. Thus, reducing the
      solubility of a protein in the external aqueous phase allows the product of
      microspheres with a better encapsulation efficiency, although this benefit is
      provided by a strong adsorption of the protein on microsphere surface.

PMID- 9651865
TI  - Clonazepam microencapsulation in poly-D,L-lactide-co-glycolide microspheres.
AB  - The work is aimed at the preparation and characterization of biodegradable
      microspheres of poly-D,L-lactide-co-glycolide (PLGA), for the controlled release
      of clonazepam. The solubility characteristics of this drug make it an interesting
      example to evaluate the performances of the two most widely used
      microencapsulation techniques, emulsification solvent evaporation and spray
      drying. Several biodegradable PLGA copolymers have been evaluated (RG 502H, RG
      503H, RG 503, Boerhinger Ingelheim). They differ in terms of molecular weight and
      physico-chemical characteristics. The microspheres obtained have been
      characterized for their morphology, physico-chemical properties (DSC) and in
      vitro dissolution behaviour. Between the two preparation methods, only spray
      drying was suitable for the microencapsulation of clonazepam in PLGA
      microspheres. In vitro dissolution tests highlight that more sustained release of
      drug is achieved with the higher (molecular weight) polymer.

PMID- 9651866
TI  - Preparation and in vitro dissolution profile of dual polymer (Eudragit RS100 and
      RL100) microparticles of diltiazem hydrochloride.
AB  - A microparticulate dosage form for a highly soluble drug, diltiazem
      hydrochloride, was formulated with Eudragit RS100 and RL100 using a novel dual
      polymer technique. A mixture of diltiazem with Eudragit RS100 (low water
      permeability) in acetone was coacervated into soft polymer microdrops, following
      which a mixture of diltiazem and RL100 (high water permeability) was added to
      produce microparticles consisting of both polymers with diltiazem dispersed in
      the matrix. A second formulation was developed using the same method except using
      Eudragit RS100 for both steps. For a comparative study, diltiazem, Eudragit RS100
      and RL100 were combined together in a single matrix and formulated into
      microparticles. In vitro drug release profiles using USP paddle dissolution
      apparatus 2 revealed that dual polymer matrix microparticles containing Eudragit
      RS100 in the inner and Eudragit RL100 in the outer core exhibit a suitable
      release profile with an initial release of the drug followed by a plateau level
      for the test period of 5 h. Differential scanning calorimetric analysis showed no
      interaction of the drug with the polymers.

PMID- 9651867
TI  - Polyamide microcapsules containing alginic acid: extractability of metal ions and
      surface characterization by XPS.
AB  - Polyamide microcapsules containing alginic acid as a water-soluble macromolecular
      ligand (Alg-MC) were prepared by the interfacial polycondensation of
      sebacoyldichloride with hexamethylenediamine in a w/o emulsion system. The mean
      diameter of the microcapsules was 1.2 microns. The extractabilities of Cu(II),
      Ni(II), Co(II) and Ag(I) into the Alg-MC were examined and the highest uptake was
      found for Cu(II). It was ascertained that not only the inner ligand solution but
      also the membrane can accumulate the metal ions. The surface composition of the
      microcapsules was characterized by X-ray photo-electron spectroscopy (XPS) and it
      was found that some functional groups of alginic acid were present at the surface
      penetrating the membrane.

PMID- 9651868
TI  - Production and antiproliferative activity of liposomes containing the antitumour
      drug chromomycin A3.
AB  - In the present paper the production and characterization of liposomes are
      described as a specialized drug delivery system for chromomycin. Liposomes were
      prepared by the reverse phase evaporation technique followed by extrusion through
      polycarbonate filters; afterwards the vesicles were characterized in terms of
      dimensions, morphology and encapsulation efficacy. The aim of this work was to
      produce a drug delivery system able to reduce the toxicity problems related to
      the administration of this drug. The analysis of the in vitro antiproliferative
      activity on cultured human leukemic K562 cells demonstrated that ionic and
      neutral liposomes containing chromomycin are 1.5 and 7-fold more effective
      respectively as compared to the free drug. Based on these results and taking into
      account the increased solubility of the drug in this system, liposomes could
      represent a promising drug delivery system for use in the experimental therapy
      using chromomycin.

PMID- 9651869
TI  - Liposomes containing boronophenylalanine for boron neutron capture therapy.
AB  - In the present work, liposomes loaded with Boronophenylalanine (BPA), with or
      without stabilization, were formulated for the application in boron neutron
      capture therapy. BPA was encapsulated into liposomes as a complex with fructose,
      but also as a free drug in two different pH buffers. The influence of critical
      variables (cholesterol content, drug:lipid molar ratio, osmotic stress of
      liposomes containing hyperosmotic drug solution) on liposome morphology and drug
      content was evaluated. The drug content and dissolution profile of different BPA
      loaded liposomes were also studied. The physical stability of liposomes in terms
      of changes in the size distribution in different osmotic pressure buffers and the
      chemical oxidation of phospholipids during storing conditions were investigated.
      The encapsulation efficiencies of all formulations were always satisfactory,
      being between 20-48%; even when the liposomes were exposed to high osmotic
      stress, the particle size was below 200 nm. The BPA-fructose complex loaded
      liposomes showed a slower drug release profile.

PMID- 9651870
TI  - Study of azathioprine encapsulation into liposomes.
AB  - The factors influencing the encapsulation of azathioprine (AZA) into liposomes
      were investigated to find out the conditions for its optimal entrapment. Similar
      studies for comparison were also carried out on 6-mercaptopurine (6-MP), of which
      AZA is a prodrug. AZA and also 6-MP show higher encapsulation efficiencies in
      MLVs as compared to LUVs. Variation in phospholipid composition does not seem to
      affect the loading capacity of either of the two drugs. The encapsulation
      efficiency of both the drugs improves upon addition of cholesterol in the
      bilayer, but the effect is seen only up to 30% cholesterol. Thereafter the effect
      becomes constant. AZA shows better incorporation in the positively charged
      liposomes as compared to those with neutral or negative charge. The entrapment of
      6-MP is, however, found to be independent of the charge on the liposomes.
      Entrapment efficiency for both the drugs markedly depends on the pH of the
      hydration medium, yielding better entrapment efficiencies at high pH values. The
      rise in solute concentration initially causes increase in the entrapment of the
      two drugs which is followed by a decreasing phase.

PMID- 9651871
TI  - Bovine serum albumin loaded poly(lactide-co-glycolide) microspheres: the
      influence of polymer purity on particle characteristics.
AB  - To study the influence of polymer purity on microsphere characteristics, bovine
      serum albumin (BSA) loaded biodegradable microspheres were prepared by spray
      drying using two samples of poly(lactide-co-glycolide), PLG, (50:50, mwt = 35 and
      69 kDa). Polymer properties were varied by DL-lactide and glycolide addition or
      by ultrafiltration. While the effective drug loading was not affected by polymer
      purity, Tg was decreased with increasing monomer and oligomer content. The
      removal of these low molecular weight substances by ultrafiltration led to a
      narrower molecular weight distribution compared to the untreated PLG. Concerning
      the polymer with the higher molecular weight, microsphere morphology was also
      strongly affected by polymer composition. In contrast to the non-modified PLG,
      monomer addition yielded particles with a much smoother surface structure.
      Moreover, in vitro cytotoxicity of the microspheres prepared from the polymer
      pretreated by ultrafiltration was significantly reduced, whereas monomer addition
      caused a dramatic decrease of cells surviving contact with the microsphere
      extract. The in vivo degradation rate of the ultrafiltered microspheres was
      decreased and as a result, protein release at later times was slowed down.
      Furthermore, depending on the effective drug loading level, monomer addition
      resulted in a decrease in the initial protein burst. It can be concluded that the
      effect of low molecular weight impurities in a polymer on microsphere
      characteristics and on cytotoxicity cannot be ignored. Their elimination is
      possible by ultrafiltration.

PMID- 9651872
TI  - Preparation of polylactic acid microcapsules containing ciprofloxacin.
AB  - Microcapsules have been used as drug delivery systems in the pharmaceutical field
      for sustained or controlled release of drug, and for artificial cells and organs.
      Biodegradable polymers, especially polylactic acid, have been widely used in this
      field. In this study, an attempt was made to develop a new method to prepare
      polylactic acid microcapsules for drug delivery. The biodegradable polylactic
      acid microcapsules were made by the phase separation process: two types of
      polylactic acid, poly[(D,L)lactic acid] and poly[(L)lactic acid] were combined as
      the membrane material. Because of the difference of the crystal properties of the
      two polymers, the aggregation which happens frequently in the phase separation
      process was prevented. As a model drug, Ciprofloxacin was encapsulated in the
      polylactic acid microcapsules.

PMID- 9651873
TI  - Comments on 'Modulation of protein release from chitosan-alginate microcapsules
      using the pH-sensitive polymer hydroxypropyl methyl cellulose acetate succinate'.

PMID- 9651874
TI  - Prevalence and natural history of periodontal disease in prehistoric Scots (pre
      900 AD).
AB  - The periodontal status of a Scottish prehistoric population was studied. No
      individual over the age of 10 yr had an entirely healthy periodontium. Gingivitis
      was the most widespread disease state in the adolescent and younger age groups.
      The progression towards periodontitis was at a constant rate and mirrored modern
      epidemiological studies. A small proportion of individuals proved to be either
      more susceptible or resistant to periodontal disease. There was no evidence of
      periodontal disease prevalence being higher than that of modern societies with
      access to dental treatment. Much can be learnt regarding the natural history of
      periodontal disease by the study of archaeological material.

PMID- 9651875
TI  - Accuracy of quantitative digital subtraction radiography for determining changes
      in calcium mass in mandibular bone: an in vitro study.
AB  - The aim of this in vitro study was to determine the accuracy of digital
      subtraction radiography (DSR) to detect small changes in calcium mass in alveolar
      bone adjacent to tooth roots. In each of 4 dried porcine mandible segments, one
      interproximal and one buccal "defect" region was defined adjacent to a premolar
      root. A series of cortical and cancellous bone slices with a 50 microns--stepwise
      increasing thickness (0-5000 microns) were attached to the mandible segments
      covering the respective "defect" region. Standardized radiographs were
      quantitatively assessed for density changes using DSR. After dissolving each bone
      slice in hydrochloric acid, its calcium concentration was photometrically
      determined. For each bone slice, the mean calcium mass covering a single pixel of
      the subtraction image was calculated. The Wilcoxon signed-rank test and the Mann
      Whitney U-test were used for statistical analysis (alpha = 0.05). A strong linear
      correlation (r2 = 0.86-1.00; p < or = 0.001) was found between the thickness of
      the bone slices and their calcium mass. Cortical bone showed a 3.5 times higher
      mean calcium mass/pixel than cancellous bone. Furthermore, a strong linear
      correlation (r2 = 0.63-1.00; p < or = 0.001) was found between the mean calcium
      mass per image pixel and the radiographic density changes. Neither the bone type
      nor the "defect" localization had a significant influence on radiographic density
      changes caused by changes in calcium mass. A change in mean calcium mass per
      image pixel of 0.1-0.15 mg was necessary to be detected by DSR. In conclusion,
      this study revealed a high accuracy of DSR to detect small changes in calcium
      mass in alveolar cortical and cancellous bone.

PMID- 9651876
TI  - The effects of cold storage and endotoxin challenge on osteoblast viability and
      interleukin-6 production.
AB  - Autogenous hip marrow is an excellent source of pluripotential cells for
      regenerative procedures. However, before this treatment modality can be employed
      a method to attenuate osteoclast activity must be developed. The shock of cold
      storage (4 degrees C) is thought to abate osteoclast activity through the
      downregulation of osteolytic cytokines produced by osteoblasts. The objective of
      this study was to evaluate the effects of cold storage (4 degrees C) and
      endotoxin challenge on bone cell culture viability and interleukin-6 (IL-6)
      production. These cells (osteoblasts) were primarily harvested from murine
      calvaria utilizing sequential digestions, separated by density gradient and
      combined. Twelve-well cell culture plates were inoculated with 2 x 10(4) cells/ml
      and placed in cold storage for 1-14 d. After cold storage the cultures were then
      incubated at 37 degrees C for 1-20 d. A set of replicate plates was also
      challenged with 10 ng/ml endotoxin upon incubation at 37 degrees C for 4
      consecutive days. Cells were evaluated daily for alkaline phosphatase activity.
      Cell culture supernatants were also collected daily and batch assayed for IL-6
      production. Cell cultures did not survive more than 48 h of cold storage. There
      was a decrease in IL-6 secretion in all refrigerated cultures and a significant
      decrease in those cells refrigerated for 48 h versus control cultures (p < 0.05).
      Replicate cultures treated with endotoxin secreted significantly increased
      amounts of IL-6 in both the control cultures and the cultures exposed to 24 h of
      cold storage versus non-endotoxin-treated control cultures (p < 0.05). These
      observations suggest that after 48 h of cold storage autogenous marrow may be
      safe to use because of the dramatic decrease in IL-6 production by osteoblasts.

PMID- 9651877
TI  - Evidence for healing of interproximal intrabony defects after conventional and
      regenerative therapy: digital radiography and clinical measurements.
AB  - In 24 patients with advanced periodontitis 38 interproximal intrabony defects
      were treated by conventional surgery (C; n = 8) or guided tissue regeneration
      (GTR) using expanded polytetrafluoroethylene (G; n = 17) or Polyglactin 910
      barriers (V; n = 13). Presurgically (BL), 6 and 12 months postsurgically clinical
      parameters (GI, PII, PPD, PAL-V) and 36 standardized radiographs were obtained
      generating 72 pairs (36 BL/6 months; 36 BL/12 months). Using linear measurements
      on the radiographs and subtraction analysis, bony fill within the defects was
      assessed. Intrasurgically the extension of the intrabony defects was measured.
      Statistically significant (p < 0.05) attachment gain was found after 6 (C: 2.4 +/
      1.6 mm; G: 3.2 +/- 1.6 mm; V: 3.4 +/- 1.5 mm) and 12 months in all groups (C:
      2.4 +/- 1.7 mm; G: 3.1 +/- 1.7 mm; V: 4.0 +/- 1.7 mm). Thirty-nine of 72 pairs of
      radiographs were unsuitable for subtraction analysis. Significant (p < 0.05) bony
      fill was observed at 6 (C: 0.3 +/- 1.0 mm; G: 0.7 +/- 1.2 mm; V: 0.9 +/- 1.2 mm)
      and 12 months (C: 0.0 +/- 1.1 mm; G: 1.4 +/- 1.5 mm; V: 1.5 +/- 1.7 mm) only
      after GTR surgery. GTR therapy yielded significantly more bony fill than
      conventional surgery 12 months postsurgically (p < 0.1). Bony fill (linear
      measurement) was influenced by age, smoking, baseline bone loss and PAL-V gain (p
      < 0.0001). Significantly more radiographs taken with potentially unstable support
      of the filmholder were not suitable for subtraction analysis than those with
      stable support (p < 0.05). Bony gain (subtraction analysis) was positively
      modulated by bony fill (linear measurement) and use of biodegradable barriers (p
      = 0.002). There is a correlation between PAL-V gain and bony fill (linear
      measurement). Smoking impairs attachment gain and bony fill. Potentially stable
      support of the filmholder provided radiographs suitable for subtraction analysis.

PMID- 9651878
TI  - Evidence that cyclosporin A administration induces the formation of new cementum
      like islets inside the gingival connective tissue.
AB  - Two groups of 3 male Sprague-Dawley rats were given orally 30 mg/kg/d of vehicle
      (control group) or cyclosporin-A (experimental group) solution for 14 wk. The
      rats were anesthetized, tissues fixed by intracardiac perfusion of fixative
      solution and jaws dissected, demineralized, processed for Epon inclusion and cut
      by semi-thin serial sections. Histological examination revealed the presence of
      several islets located paravascularly inside the gingival connective tissue in
      the proximity of the root surfaces. The structure of these new cementum-like
      islets (NCLIs) was either compact and homogeneous or heterogeneous, but identical
      to that of the adjacent new cementum (NC) deposits. Histomorphometric evaluation
      indicated that the volume and the external surface of the NCLIs varied from 2354
      to 679,497 micron 3 and from 465 to 47,517 micron 2, respectively. These
      observations (a) suggest that CsA stimulates possibly paravascular progenitor
      cells which secrete in situ a NC-like material and (b) provides further evidence
      about the high potential of CsA to induce NC formation.

PMID- 9651879
TI  - A digital subtraction radiography investigation of upper first molar proximal
      bone density changes in adolescents.
AB  - The aim of this in vivo study was to investigate the ability of digital
      subtraction radiography to monitor changes in proximal bone density, adjacent to
      the upper first molars, in a group of adolescents using the Digora direct digital
      radiographic system to acquire images. For 57 adolescents, assessments of changes
      in probing attachment level at the mesio- and disto-buccal surfaces of both upper
      first molars and proximal crestal bone density using digital subtraction
      radiography were made. At the conclusion of this 21-month study attachment loss
      was identified in 34 (17%) of the 204 sites analysed. For sites with attachment
      loss a mean decrease in bone density equivalent to 5.51 mm3 aluminium (Al) was
      found compared to 2.96 mm3 Al for those without (p < 0.001). For the 17 subjects
      with attachment loss a mean equivalent to 4.66 mm3 Al was lost from the crestal
      bone compared with 2.56 mm3 Al for the 40 subjects without attachment loss (p <
      0.01). The correlation between attachment loss and bone density changes was poor
      for both sites (r = 0.13), p = 0.067) and mean scores for subjects (r = 0.24, p =
      0.069). A visual qualitative assessment of bone density change found that 70.6%
      of sites with attachment loss compared to 62.4% of those without had a decrease
      in crestal bone density. This study suggests that it is possible to monitor bone
      density changes in adolescents, with a developing dentition, using digital
      subtraction radiography. Further, it is suggested that conventional probing
      assessments of attachment level may underestimate the level of destructive
      periodontal disease in this age group.

PMID- 9651880
TI  - [3H]5,7-dichlorokynurenic acid recognizes two binding sites in rat cerebral
      cortex membranes.
AB  - Binding of [3H]5,7-dichlorokynurenic acid ([3H]DCKA), a competitive antagonist of
      the strychnine-insensitive glycine site of the N-methyl-D-aspartate (NMDA)
      receptor channel complex, was characterized in synaptic plasma membranes from rat
      cerebral cortex. Non linear curve fitting of [3H]DCKA saturation and homologous
      displacement isotherms indicated the existence of two binding sites: a specific,
      saturable, high affinity site, with a pKD value of 7.24 (KD = 57.5 nmol/l) and a
      maximum binding value (Bmax) of 6.9 pmol/mg of protein and a second site, with
      micromolar affinity. The pharmacological profile of both binding components was
      determined by studying the effect on [3H]DCKA and [3H]glycine binding of a series
      of compounds known to interact with different excitatory and inhibitory amino
      acid receptors. These studies confirmed the identity of the high affinity site of
      [3H]DCKA binding with the strychnine-insensitive glycine site of the NMDA
      receptor channel complex. 3-[2-(Phenylaminocarbonyl)ethenyl]-4,6-dichloroindole-2
      carb oxylic acid sodium salt (GV 150526A), a new, high affinity, selective
      glycine site antagonist (1), was the most potent inhibitor of this component of
      binding (pKi = 8.24, Ki = 5.6 nmol/l). The low affinity component of [3H]DCKA
      binding was insensitive to the agonists glycine and D-serine and the partial
      agonist (+/-)-3-amino-1-hydroxy-2-pyrrolidone (HA 966), though recognised by
      glycine site antagonists. The precise nature of this second, low affinity
      [3H]DCKA binding site remains to be elucidated.

PMID- 9651881
TI  - PEST sequences in proteins involved in cyclic nucleotide signalling pathways.
AB  - There is growing evidence that PEST sequences act as proteolytic recognition
      signals within polypeptides. PEST sequences are rich in proline (P), glutamic
      acid (E), serine (S), and threonine (T) and can be identified by the PEST-FIND
      program. Both the catalytic and regulatory subunits of the cAMP-dependent protein
      kinase have been shown to have conditional PEST sequences which are exposed upon
      cAMP binding to the enzyme. cAMP binding leads to rapid dissociation of C- and R
      subunits, and both subunits have increased sensitivity to proteolysis. It is not
      known whether other proteins that participate in the cyclic nucleotide signalling
      pathway have PEST regions in their amino acid sequences. Therefore, we have
      screened amino acid sequences of proteins that are directly involved in cyclic
      nucleotide cascade, including cGMP-dependent protein kinases, anchoring proteins
      for cAMP-dependent protein kinase, cyclic nucleotide-gated ion channels, and
      cyclic nucleotide phosphodiesterases, for PEST sequences using the PEST-FIND
      program. Many PEST sequences with high scores have been identified in these
      proteins. The occurrence of the PEST sequences is very high in proteins involved
      in cyclic nucleotide signalling pathways (approximately 80%). This value is much
      higher than the percentage (10%) of PEST sequences that can be found in the
      primary structures of the proteins listed in the data bank. This frequent
      occurrence of PEST sequences in proteins involved in cyclic nucleotide action and
      metabolism suggests an important role of proteolysis of these key proteins of
      signal transduction.

PMID- 9651882
TI  - Mapping of dopamine D3 receptor binding site by pharmacological characterization
      of mutants expressed in CHO cells with the Semliki Forest virus system.
AB  - Nine mutants and the wild-type human dopamine D3 receptor were expressed at high
      levels in BHK and CHO cells using the Semliki Forest virus system and were
      analysed for receptor binding with several structurally different dopamine D3
      ligands. The mutation His349Leu showed a significant decrease in pKi values for
      raclopride, dopamine and GR218231, but an increase in affinity for GR99841.
      Thr369Val had an increase in pKi for both GR99841 and 7-OH-DPAT. The receptor
      modelling based on sequence alignment with bacteriorhodopsin indicated that
      Thr369 and His349 are located on the inside of the ligand binding pocket and the
      effect of the mutagenesis was therefore expected. The change in binding affinity
      for Thr369Val could be due to the location in the transmembrane domain VII close
      to the aspartate residue in domain III, the postulated counter ion for dopamine.

PMID- 9651883
TI  - Characterization of muscarinic cholinergic receptor subtypes in rat prostate.
AB  - The purpose of this study was to characterize the muscarinic receptor subtypes in
      the individual lobes of the rat prostate. Immunoprecipitation was performed on
      homogenates of these 3 lobes using antibodies to the m1-m4 muscarinic receptor
      subtypes. Reverse transcriptase polymerase chain reaction assays (RT-PCR) were
      also performed using primers specific for each of the five muscarinic receptor
      subtypes (m1-m5). The susceptibility of the receptors to degradation by
      endogenous prostate proteases was assessed by mixing rat ventral prostate with
      rat heart (m2) and rat parotid (m3) prior to immunoprecipitation. In the ventral
      lobe, transcripts for the m1-m4 subtypes were amplified whereas in the dorsal and
      lateral lobes only the m2 and m3 sets of primers amplified PCR products of the
      predicted size. Immunoprecipitation of the ventral lobe resulted in predominantly
      m3 receptors, while the majority of receptors immunoprecipitated from lateral and
      dorsal lobes were the m2 subtype. The m3 muscarinic subtype was apparently
      susceptible to degradation by prostate proteases whereas the m2 subtype was not.
      These results demonstrate a regional distribution in the subtypes of muscarinic
      receptors in the rat prostate, and a greater susceptibility of the m3 receptor to
      degradation during immunoprecipitation than the m2 subtype.

PMID- 9651884
TI  - Redox regulation of signal transduction in smooth muscle cells: distinct effects
      of PKC-down regulation and PKC inhibitors on oxidant induced MAP kinase.
AB  - Reactive oxygen species function as signaling molecules, and are known to be
      generated under both normal and pathological conditions. Using vascular smooth
      muscle cells, we have demonstrated an increase in mitogen activated protein
      kinase activity in response to oxidants. Mitogen activated protein kinase
      activity increased linearly with time in cells treated with pervanadate. Hydrogen
      peroxide also caused rapid induction of mitogen activated protein kinase. Protein
      kinase C down regulation partially decreased induction of mitogen activated
      protein kinase activity by oxidants, and the Ca2+ ionophore, ionomycin. Protein
      kinase C inhibitors, compound-3 and bisindolylmaleimide did not inhibit oxidant
      induced mitogen activated protein kinase activity, where as calphostin C
      activated it. The tyrosine kinase inhibitors genistein, herbimycin A and
      tyrphostin caused 50% inhibition of oxidant induced mitogen activated protein
      kinase activation. These results suggest that oxidant-induced mitogen activated
      protein kinase is protein kinase C independent.

PMID- 9651885
TI  - Strategies for positioning fluorescent probes and crosslinkers on formyl peptide
      ligands.
AB  - Chemoattractant receptors represent a major subset of the G-protein coupled
      receptor (GPCR) family. One of the best characterized, the N-formyl peptide
      receptor (FPR), participates in host defense responses of neutrophils. The
      features of the ligand which regulate its interaction with the FPR are well
      known. By manipulating these features we have developed new ligands to probe
      structural and mechanistic aspects of the peptide-receptor interaction. Three
      ligand groups have been developed: 1) ligands containing a Lys residue located in
      positions 2 through 7 that can be conjugated to FITC (N-formyl-Met1-Lys2-Phe3
      Phe4, N-formyl-Met1-Leu2-Lys3-Phe4, N-formyl-Met1-Leu2-Phe3-Lys4, N-formyl-Met1
      Leu2-Phe3-Phe4-Lys5, N-formyl-nLeu1-Leu2-Phe3-nLeu4-Tyr5-Lys6 and N-formyl-Met1
      Leu2-Phe3-Phe4-Gly5-Gly6-Lys7; 2) fluorescent pentapeptide ligands (N-formyl-Met
      X-Phe-Phe-Lys(FITC) where X = Leu, Ala, Val or Gly); and 3) small crosslinking
      ligands where the photoaffinity crosslinker 4-azidosalicylic acid (ASA) was
      conjugated to Lys in positions 3 and 4 and p-benzoyl-phenylalanine (Bpa) was
      located in position 2 in N-formyl-Met1-Bpa2-Phe3-Tyr4. The peptides were
      characterized according to activity and affinity in human neutrophils and cell
      lines transfected with FPR. All of the peptides were agonists, with parallel
      affinity and activity. In the first group, the peptide activity decreases as Lys
      is placed closer to the N-formyl group and the activity is improved by 1-3 orders
      of magnitude by conjugation with FITC. In the second group, the dissociation rate
      of the peptide from the receptor increases as position 2 is replaced by aliphatic
      amino acids with smaller alkyl groups. In the third group, crosslinking ligands
      remain biologically active, display nM affinity and covalently label the FPR.

PMID- 9651886
TI  - Finite element modelling of bulk muscular tissue.

PMID- 9651887
TI  - Biomaterials in the 21st century revisited!

PMID- 9651888
TI  - Material properties of commonly-used interface materials and their static
      coefficients of friction with skin and socks.
AB  - Compressive stiffness (CS) of different supporting materials used in prosthetics
      and orthotics and their static coefficients of friction (COF) with skin and socks
      were characterized. Materials tested included Spenco, Poron, nylon-reinforced
      silicone, Soft Pelite, Medium Pelite, Firm Plastazote, Regular Plastazote, and
      Nickelplast. A displacement-controlled testing device was constructed to assess
      the CS of 11.1 mm diameter material specimens under cyclic loading (1 Hz) to 220
      kPa over 10- and 60-min periods. Results demonstrated local CS ranging from 687
      kPa (Poron) to 3,990 kPa (Soft Pelite). To fit the cyclic stress-strain (S-S)
      data within an error of 4.0 percent full-scale output, the minimum order of fit
      required for Spenco, Poron, and nylon-reinforced silicone was a third-order
      polynomial; for Soft Pelite, Medium Pelite, Firm Plastazote, and Regular
      Plastazote, a second-order polynomial; and for Nickelplast, a linear fit. For all
      materials, the nonrecovered strains were related to loading time using an
      exponential fit. A biaxial force-controlled load applicator device was used to
      assess COF at skin-material, sock-material, and skin-sock interfaces for shear
      forces of 1 to 4 N applied to a 10.2 x 7.8 mm loading pad. COFs ranged from 0.48
      (+/- 0.05) to 0.89 (+/- 0.09). COFs at skin-material interfaces were
      significantly (p < 0.05) higher than those at skin-sock interfaces. There was a
      trend of a higher COF at sock-material interfaces than at skin-sock interfaces.
      These data are of potential utility in finite element modeling sensitivity
      analysis of residual limb-prosthetic socket systems or body-orthosis systems to
      characterize effects of material features on interface pressure and shear stress
      distributions.

PMID- 9651889
TI  - Mechanical efficiency during gait of adults with transtibial amputation: a pilot
      study comparing the SACH, Seattle, and Golden-Ankle prosthetic feet.
AB  - As more and more prosthetic feet become commercially available, the selection of
      the appropriate device is a more difficult task for clinical team members. To
      date, ranking prosthetic feet based on biomechanical parameters has been done
      using the spring efficiency. The current analytical technique for calculating
      spring efficiency has two flaws: first, prosthetic feet with a bendable flexible
      keel are analyzed the same way as those with an articulated ankle and a rigid
      foot, and second, there is no accounting for the energy losses in the
      viscoelastic cosmetic material surrounding the keel. This paper develops a
      rigorous technique to calculate the net energy stored or dissipated and then
      recovered during the stance phase of gait. Five adults with transtibial
      amputation were tested with three different prosthetic feet: SACH, Seattle, and
      Golden-Ankle. The subjects walked at self-selected cadence and stepped on a force
      plate while two-dimensional segmental kinematic and kinetic data were collected.
      The results showed that the Golden-Ankle stored or dissipated and then recovered
      significantly more energy than either the SACH or Seattle. The time to reach foot
      flat was also significantly reduced for the Golden-Ankle in comparison to both
      the others. Because the cosmetic material of the SACH foot can store or dissipate
      and then recover as much energy as the Seattle foot, the SACH foot should be
      considered an energy-storing foot. Finally, the net efficiency alone can not
      discriminate adequately among different types of prosthetic feet; therefore, one
      should consider the time to reach foot flat and the amount of energy recovered as
      additional objective criteria (weight, maintenance, and cosmesis) for selection
      of a prosthetic foot device.

PMID- 9651890
TI  - Validation of F-Scan pressure sensor system: a technical note.
AB  - This study performed a quantitative validation on a recently developed pressure
      sensitive transducer system, the F-Scan sensor system. The results indicate that
      the sensor is adequate for determination of pressure distribution under contact
      conditions with soft materials. The linear response of the sensor was up to 1.7
      MPa with good homogeneity throughout sensor cells. However, the sensor is
      sensitive to surface conditions, loading speeds, and temperature. Variations also
      exist from sensor to sensor. In order to have accurate measurement, calibration
      was recommended in actual clinical or experimental conditions prior to use,
      including surface contact conditions, loading speeds, and temperature
      environment. In addition, this sensor system is not suitable for hard surface
      contact such as plexiglas.

PMID- 9651891
TI  - Sensing stability and dynamic response of the F-Scan in-shoe sensing system: a
      technical note.
AB  - The objective of this study was to gain a better understanding of the F-Scan to
      determine its appropriate clinical application. Vertical pressure was applied to
      a sensor foil over the range of 10-80 kPa with or without the intervention of 0.2
      0.8 mm thick felt. Sensor sensitivity reached a maximum without the felt, and
      decreased with increasing felt thickness, stabilizing at 48-74% of the maximum
      level when felt thickness exceeded 0.4 mm. This sensitivity change was caused by
      the slight difference in thickness of sensing areas from that of non-sensing
      areas. Dynamic response time was delayed by a mean of 0.32 s. Although the cause
      of this dynamic response delay remains unclear, it was considered to be
      inappropriate for accurate dynamic measurements. Therefore, rather than using F
      Scan measurement to accurately obtain actual values, it should be used for
      relative comparisons of the plantar pressure distributions under constant
      conditions.

PMID- 9651892
TI  - Methods for reducing energy dissipation in cosmetic gloves.
AB  - For cosmetic reasons, hand prostheses are provided with cosmetic gloves. Their
      pleasing appearance, however, is accompanied by poor mechanical behavior,
      resulting in a negative influence on prosthesis operation. Glove stiffness is
      high and nonlinear, and internal friction in the glove material causes energy
      dissipation (hysteresis). In this article, two methods for reducing hysteresis in
      cosmetic gloves are proposed, that may be applied independently or in
      combination. Glove modification. Altering the mechanical properties of the glove
      itself is the first method that is presented. It was found possible to reduce
      both stiffness and hysteresis about 50% by forming grooves into the inside of the
      glove. Together with the evaluation of this method, several properties of the
      cosmetic glove were determined. Motion optimization. Additionally, a second
      method for reducing hysteresis was developed. The amount of hysteresis is
      influenced by the way the glove is forced to deform. The prosthesis mechanism,
      determining this deformation, was designed for minimum hysteresis and maximum
      cosmesis. For the prosthesis-glove combination used in this study, thumb motion
      optimization reduced hysteresis by about 65%.

PMID- 9651893
TI  - Kinematic characterization of wheelchair propulsion.
AB  - Rehabilitation scientists and biomedical engineers have been investigating
      wheelchair propulsion biomechanics in order to prevent musculoskeletal injuries.
      Several studies have investigated wheelchair propulsion biomechanics; however,
      few have examined wheelchair propulsion stroke patterns. The purpose of this
      study was to characterize wheelchair propulsion stroke patterns by investigating
      joint accelerations, joint range of motions, wheelchair propulsion phases, and
      stroke efficiency. Seven experienced wheelchair users (5 males, 2 females) were
      filmed using a three-camera motion analysis system. Each subject pushed a
      standard wheelchair fitted with a force-sensing pushrim (SMARTWheel) at two
      speeds (1.3 and 2.2 m/s). The elbow angle was analyzed in the sagittal plane,
      while the shoulder joint was analyzed in the sagittal and frontal planes. Three
      distinctly different stroke patterns: semi-circular (SC), single looping-over
      propulsion (SLOP), and double looping-over-propulsion (DLOP), were identified
      from the kinematic analysis. Through our analysis of these patterns, we
      hypothesized that SC was more biomechanically efficient than the other stroke
      patterns. Future studies using a larger number of subjects and strokes may reveal
      more significant distinctions in efficiency measures between stroke patterns.

PMID- 9651894
TI  - Polyurethane foams: effects of specimen size when determining cushioning
      stiffness.
AB  - Polyurethane (PU) foams are used as inexpensive materials for reducing interface
      pressure in a number of rehabilitative applications, particularly seating and
      prosthetic limb interfaces. Specimens of three different PU foams were cut to
      four different sizes and compressed according to ASTM protocols to determine
      their stiffness capabilities. It was found that the test results varied according
      to the relationship between the size of the test specimen and the test indenter.
      It is recommended that investigators create a testing situation that reflects
      their application when determining the cushioning capabilities of these
      materials.

PMID- 9651895
TI  - Assessment of alternating air mattresses using a time-based interface pressure
      threshold technique.
AB  - Laboratory evaluation techniques for support surfaces have centered largely
      around interface pressure (IP) measurement, typically analyzing discrete maximum
      and minimum levels, or calculating the average pressure. Nowadays, alternating
      pressure air mattresses (APAMs) are used increasingly for the prevention and
      treatment of pressure sores. Pressure relief (PR) provided by an APAM is time
      varying. A computerized system that measures IP, air pressure, and pressure-time
      characteristics of dynamic support surfaces has been developed for performance
      assessment. Using this system, IP was recorded continuously and the durations of
      pressures below three thresholds (30, 20, and 10 mmHg) were calculated
      automatically. Fifteen sound volunteers were used to evaluate the pressure
      relieving characteristics of four APAMs, including one overlay. Results indicated
      significant differences (p < 0.001) between products when durations below 20 and
      10 mmHg thresholds were analyzed, showing some devices were only capable of
      momentarily relieving pressure. Maximum contact pressures on the sacrum were
      significantly lower (p < 0.0001) on devices where inflation pressure was adjusted
      according to the body mass of the subject. With further clinical validation, this
      tool could assist in the selection of alternating surfaces of any description.

PMID- 9651896
TI  - The relationship between gait parameters and pain in persons with transtibial
      amputation: a preliminary report.
AB  - This is a preliminary study of the potential relationship between pain and gait
      parameters in 11 persons with transtibial amputation who underwent gait analysis
      under both baseline and discomfort walking conditions. Gait analysis included
      measurement with a VA-Rancho Stride Analyzer of the following gait parameters:
      velocity, cadence, stride length, gait cycle, and support time. These data were
      correlated with pain intensity data determined with a standard Visual Analog
      Scale. Wide ranges of discomfort were reported and corresponding alterations in
      gait parameters varied greatly in both magnitude and quality. There was no
      obvious pattern in acclimation to discomfort. A significant correlation was found
      between pain intensity and the magnitude of change in velocity (p < 0.05). In
      addition, all subjects reporting significant pain (> 33% of maximum) slowed down,
      while gait alterations of others varied widely in response to the experience of
      pain. Further studies with a larger and more homogeneous subject pool to examine
      these relationships fully are recommended to follow this preliminary report.

PMID- 9651897
TI  - An assistive device for persons with severe amnesia.
AB  - Five persons with severe amnesia were trained to use a device containing items of
      information relevant to daily activities. The training consisted of a procedure
      in which requests for information were paired with a tone, and the subject was
      required to access the device and respond with the answer to the request. The
      tone was gradually faded, with the goal of having the subject respond to a
      question alone. All of the subjects learned to consistently access the device and
      provide correct responses following a request for information. Generalization
      across requesters and settings in which the requests were made was also achieved.
      The findings are discussed in regard to the utility of exploiting the relatively
      well-preserved procedural memory system for rehabilitation of persons with severe
      amnesia.

PMID- 9651898
TI  - A validation study on status and age of natural menopause reported in the E3N
      cohort.
AB  - The accuracy of self-reported menopausal status and age at menopause has been
      analysed in a validation study using the gynecologist's medical records as the
      reference. Concordance between the two sources for menopausal status was assessed
      in 151 women. The kappa coefficient obtained was 0.85 (95% CI, 0.69-1.00).
      Agreement on age at menopause was tested in 57 women and the kappa coefficient
      obtained was 0.64 (95% CI, 0.34-0.94). Age at menopause was accurately reported
      by 32% of the subjects. This percentage increased to 69 and 86% when agreement
      within 1 and 2 year(s) was considered, respectively. These results suggest that
      women can provide data on their natural menopause history with sufficient
      accuracy to test some hypotheses associating this event with the evolution of
      their health status.

PMID- 9651899
TI  - Association of diet and other lifestyle with onset of menopause in Japanese
      women.
AB  - OBJECTIVES: To evaluate the cross-sectional relationships of dietary and other
      lifestyle variables to menopause. METHODS: A total of 4186 female residents aged
      45-55 in Takayama City, Japan, responded to a self-administered questionnaire
      (the response rate was 89.3%). Diet in the past year was assessed by
      semiquantitative food frequency questionnaire. Using the logistic regression
      model, associations between study variables and menopausal status were estimated
      in terms of odds ratio (OR). RESULTS: Nulliparity and lower relative weight were
      significantly associated with menopause after controlling for age (P < 0.05). The
      association of smoking with menopause was marginally significant after
      controlling for age (P = 0.06). Higher intakes of fat, cholesterol, and coffee
      were inversely and significantly associated with later menopause after
      controlling for age, total energy, parity, menarche age, and relative weight (ORs
      for the highest tertiles of fat, cholesterol and coffee intakes were 0.78, 0.79,
      and 0.70, respectively, P < 0.05). The highest tertiles of calcium and soy
      product intakes were significantly associated with menopause after controlling
      for the covariates (ORs = 1.25 and 1.42, respectively, P < 0.05), but
      postmenopausal women who had menopause at later age showed higher calcium intake
      than those who had menopause at early age. CONCLUSION: Dietary factors appear to
      be associated with onset of menopause.

PMID- 9651900
TI  - Menstrual cycle length preceding menopause in relation to age at menopause.
AB  - OBJECTIVES: In one of the earlier hypotheses of the etiology of breast cancer
      (Korenman's 'oestrogen window' hypothesis (1981)), it was assumed that women with
      a later age at menopause have a longer period with irregular cycles preceding
      menopause than women with an early menopause. This assumption was tested in a
      prospective study. METHODS: Subjects were 628 women, born between 1932 and 1941,
      who had participated in a breast cancer screening project in Utrecht, The
      Netherlands (the DOM-project) in 1982-1985, and who were still menstruating at
      that time. The women had filled out a questionnaire and a menstrual calendar
      every 2 years to determine their age at menopause prospectively. The women had
      not used oral contraceptives or medicines for menopausal complaints and had
      reached natural menopause by 1992. The median of the mean menstrual cycle length
      per woman and the median of the standard deviation of the mean menstrual cycle
      length per woman were plotted against number of years prior to menopause in three
      categories of age at menopause (44-49; 50-54; 55-59). RESULTS: During the 9 years
      prior to menopause, women with a late age at menopause have a somewhat higher
      mean menstrual cycle length than women with a younger age at menopause (P =
      0.0008). Cycle length variability in the 9 years prior to menopause is not
      statistically significantly different between the three categories of age at
      menopause (P = 0.16). CONCLUSIONS: The assumption that women with a late age at
      menopause have a longer period with irregular cycles than women with an earlier
      age at menopause was not corroborated by our results.

PMID- 9651901
TI  - Duration of hormonal replacement therapy in general practice; a follow-up study.
AB  - OBJECTIVES: To assess the mean duration of use of HRT in general practice and to
      identify determinants of the duration of HRT use. METHODS: A general population
      of 1689 women aged 45-60 years and enlisted in five group practices of general
      practitioners were followed for 9 months to trace first HRT prescriptions. All
      103 women who were prescribed HRT were followed for a period of 2.25 years.
      Duration of HRT was assessed by using the data provided on the dispensing of HRT.
      Possible determinants of duration of use, such as attitude towards menopause,
      menopausal status and another six variables were measured by means of a
      questionnaire. RESULTS: None of the 103 women received HRT for a preventive
      purpose; the main indication was menopausal complaints. More than 60% of the
      women stopped their HRT within 6 months and only 8% of the women remained on HRT
      for more than 2 years. The mean duration of use was 7 months. Determinants that
      significantly predicted the duration of HRT use were age, attitude towards
      treatment of the menopause and the group practice. CONCLUSIONS: The mean duration
      of HRT use is very short, despite the fact that the most prevalent indication is
      the alleviation of menopausal symptoms. Apparently, Dutch women are presently
      unwilling to take HRT for longer periods.

PMID- 9651902
TI  - The effect of hysterectomy and endometrial ablation on follicle stimulating
      hormone (FSH) levels up to 1 year after surgery.
AB  - OBJECTIVES: In this study the hypothesis was tested, that in premenopausal
      patients FSH-levels would rise after 'simple hysterectomy'. As endometrial
      ablation is not supposed to compromise ovarian bloodflow, there would be no such
      change in ablated patients. METHODS: Between January 1995 and April 1996,
      consecutive premenopausal patients with dysfunctional uterine bleeding who were
      scheduled for hysterectomy or endometrial ablation were asked to participate in
      the study. Bloodsamples were drawn before surgery, six weeks, six months and one
      year after surgery. FSH and oestradiol (E2) were assayed. In all patients data
      about length and weight were collected to calculate Body Mass Index (BMI). Every
      visit patients filled in a questionnaire, containing questions about typical
      climacteric complaints, combined in a five-point scale. RESULTS: Except for a
      significant difference in preoperative FSH-level between both groups, there were
      no significant differences regarding age, Body Mass Index (BMI), oestradiol (E2)
      or the percentage of women with vasomotor complaints. Compared to the
      preoperative starting level, six weeks, six months and one year after surgery a
      significant rise in serum FSH in the hysterectomy group, as well as in the
      ablation group was found. However there was no significant difference in FSH
      increase between both groups. One third of the patients in both groups had
      typical climacteric complaints as flushing and nocturnal sweating. CONCLUSIONS:
      Assaying serum FSH-levels before and after uterine surgery and comparing
      hysterectomized patients and patients after endometrial ablation, we found a
      significant rise in FSH-level up to one year after surgery in both groups
      postoperatively, indicating impaired ovarian function. There was no difference in
      FSH-levels between both groups. Therefore major uterine surgery (hysterectomy,
      ablation) may prelude an earlier onset of menopause.

PMID- 9651903
TI  - Physical exercise and vasomotor symptoms in postmenopausal women.
AB  - BACKGROUND: The mechanisms causing postmenopausal vasomotor symptoms are unknown,
      but changes in hypothalamic beta-endorphins have been suggested to be involved.
      beta-endorphin production may be increased by regular physical exercise.
      OBJECTIVE: To assess if physically active women suffered from vasomotor symptoms
      to a lower extent than sedentary women. MATERIAL AND METHODS: All women (n =
      1323) in the ages ranging from 55-56 years in the community of Linkoping Sweden,
      were included. In a questionnaire these women were asked about their physical
      exercise habits and their complaints from vasomotor symptoms. Only those 793
      women who had reached a natural menopause were grouped into sedentary, moderately
      or highly active women, based on a physical activity score. RESULTS: Only 5% of
      highly physically active women experienced severe hot flushes as compared with 14
      16% of women who had little or no weekly exercise (P < 0.05; relative risk 0.26;
      CI 95%: 0.10-0.71). This was not explained by differences in body mass index,
      smoking habits or use of hormone replacement therapy. Women who used hormone
      replacement therapy were more physically active than non-users (P < 0.05).
      CONCLUSION: Fewer physically active women had severe vasomotor symptoms compared
      with sedentary women. This may be due to a selection bias but also to the fact
      that physical exercise on a regular basis affects neurotransmitters which
      regulate central thermoregulation.

PMID- 9651904
TI  - Influence of bilateral oophorectomy upon lipid metabolism.
AB  - OBJECTIVES: Reduction in serum level of estrogen has been thought to result in
      hyperlipidemia which triggers atherosclerosis, and even to lead to cardiovascular
      diseases, in postmenopausal women. The present study was designed to investigate
      the influence of bilateral oophorectomy (OPX), which induces as much reduction in
      serum estrogen level as menopause, upon lipid metabolism, especially the serum
      levels of total cholesterol. METHODS: In 31 OPX subjects and 31 age- and body
      size-matched premenopausal controls, the serum levels of total cholesterol (TC),
      triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density
      lipoprotein cholesterol (LDL-C), very low-density lipoprotein (VLDL-C),
      apoprotein-A1 (Apo-A1), apoprotein-B (Apo-B), lipoprotein lipase (LPL) and
      lipoprotein-a [LP(a)] were measured as indices of lipid metabolism and the index
      of arteriosclerosis was calculated. RESULTS: TC level was significantly higher in
      the OPX group than in the premenopausal control group, being 8995 +/- 244 (mean
      +/- S.E.) mmol/l and 7757 +/- 228 mmol/l, respectively. LDL-C and Apo-B levels
      and the index of arteriosclerosis were all significantly higher in the OPX group
      than in the premenopausal control groups. However, there were no significant
      intergroup differences with regard to HDL-C, Apo-A1, LPL and LP(a). CONCLUSIONS:
      The above results demonstrated that, in spite of no reduction in HDL-C, the blood
      levels of Apo-B, LDL-C and TC change due to OPX. These changes suggest OPX
      induces cardiovascular diseases and, therefore, follow-up of the changes in lipid
      metabolism is required, paying special attention to Apo-B and LDL-C.

PMID- 9651905
TI  - Postmenopausal hormone replacement therapy and autoantibodies against oxidized
      LDL.
AB  - OBJECTIVES: Oxidative modification of low-density lipoprotein (oxLDL) has been
      suggested to play an important role in the pathogenesis of atherosclerosis, and
      autoantibodies against oxLDL have recently found to reflect this process. The
      antioxidant effect and inhibition of LDL oxidation may be one of the
      cardioprotective mechanisms of postmenopausal estrogen therapy. METHODS: The
      effects of postmenopausal hormone replacement therapy (HRT) on the concentrations
      of serum lipids and oxLDL autoantibodies were studied in a population-based
      prospective 1-year study with 64 early postmenopausal women (mean age 52.2 +/-
      0.4 (S.E.M.) years). The participants were randomized into two treatment groups:
      HRT-group: Sequential combination of 2 mg estradiol valerate and 1 mg cyproterone
      acetate alone or in combination with vitamin D3, 300 IU/day + calcium lactate,
      500 mg/day (n = 31) and the non-HRT-group: Calcium lactate, 500 mg/day alone or
      in combination with vitamin D3, 300 IU/day (n = 33). The groups were well matched
      regarding age, body mass index and baseline serum lipid concentrations. RESULTS:
      The serum concentrations of total cholesterol and LDL-cholesterol decreased in
      the HRT-group (4.1%, P = 0.05 and 6.4%, P = 0.03, respectively, paired t-test)
      but did not change in the non-HRT-group. No changes in the serum concentrations
      of HDL-cholesterol or triglycerides were observed. Additionally, no changes in
      oxLDL autoantibody concentrations were observed in either group. CONCLUSIONS:
      Although 1-year HRT lowered serum total- and LDL-cholesterol levels, it did not
      influence oxLDL antibody titers. On the basis of the present results we cannot
      question the possibility of there being beneficial effects of HRT on the
      oxidative modification of LDL. However, this effect is not reflected in the
      levels of oxLDL autoantibodies.

PMID- 9651906
TI  - Effect of a HMG-CoA reductase inhibitor combined with hormone replacement therapy
      on lipid metabolism in Japanese women with hypoestrogenic lipidemia: a
      multicenter double-blind controlled prospective study.
AB  - OBJECTIVES: Menopause is associated with a rise in serum lipid concentrations. We
      compared a regimen of pravastatin alone with pravastatin and hormone therapy in
      postmenopausal women with hyperlipidemia. METHODS: We performed a double-blind,
      randomized, multicenter controlled study in postmenopausal women with
      hyperlipidemia. The women were randomly assigned to receive pravastatin alone (M
      group; n = 25) or pravastatin and hormone replacement therapy (HRT) (MC group; n
      = 32) for 12 weeks. Serum lipid and estrogen concentrations were measured at
      baseline and after 4 weeks and 12 weeks of treatment. RESULTS: The two groups
      were similar with respect to baseline demographic characteristics such as age,
      height, and body weight. As compared with baseline, the total cholesterol (TC)
      concentration was 15.0% lower at 4 weeks and 17.7% lower at 12 weeks in the M
      group and 15.1% lower at 4 weeks and 18.3% lower at 12 weeks in the MC group. The
      low-density-lipoprotein cholesterol (LDL-C) concentration decreased by 25.0% at
      both 4 weeks and 12 weeks in the M group and by 26.8% at 4 weeks and 30.0% at 12
      weeks in the MC group. Serum TC and LDL-C concentrations were significantly lower
      in the MC group than in the M group after 4 weeks of treatment, but there was no
      significant difference between the groups in serum lipid concentrations after 12
      weeks. Pravastatin combined with HRT was therefore suggested to lower serum lipid
      concentrations earlier than pravastatin alone. There were no significant
      differences between the treatment groups in serum high-density-lipoprotein
      cholesterol concentrations or triglyceride concentrations after the initiation of
      therapy. In the MC group, there was a significant positive correlation between
      the percentage change in serum lipid concentrations and that in estrogen
      concentrations, suggesting that the HRT-induced rise in estrone (E1) as well as
      that in estradiol (E2) contributed an improved serum lipid profile. TC and E2,
      and LDL-C and serum E1 had significant negative correlation at 12 weeks and 4
      weeks, respectively. Pravastatin had no apparent effect on endogenous estrogen
      levels and was not associated with any side effects, which confirmed that
      pravastatin is safe, either alone or in combination with HRT. CONCLUSIONS: The
      combination of pravastatin and HRT in the management of hyperlipidemia in
      postmenopausal women is very useful therapeutically, because it additionally
      provides the broad benefits of HRT, without compromising the lipid lowering
      effects of either treatment.

PMID- 9651907
TI  - T score of trabecular and cortical bone in normal postmenopausal women.
AB  - OBJECTIVE: The T score of the cortical and trabecular bone compartments (T score
      of BMDTrab and T score of BMDCorti) was calculated in healthy postmenopausal
      women to determine which bone compartment loses more bone mass. MATERIAL AND
      METHODS: A total 134 healthy postmenopausal women (mean age 55.1 +/- 6.4 years)
      and 67 healthy premenopausal women (mean age 36.0 +/- 8.6 years) were studied.
      Determinations were made using peripheral quantitative computed tomography (pQCT)
      of the nondominant forearm. The postmenopausal women were divided into groups by
      years since menopause (YSM): two early postmenopausal groups: < 5 YSM and 6-10
      YSM; and two late postmenopausal groups: 11-20 YSM and > 20 YSM. RESULTS: There
      was a significant correlation between the T score of BMDTrab and the T score of
      BMDCorti (P < 0.0001). Both correlated negatively and significantly with age (P <
      0.001 and P < 0.0001, respectively) and neither correlated with weight. The
      Wilcoxon test showed no significant differences between the trabecular and
      cortical T scores in the overall group of women. By YSM, only the > 20 YSM group
      showed significant differences (P < 0.005). The ANOVA post hoc Bonferroni/Dunn
      test showed a significant difference in the T score of BMDTrab by YSM only in the
      < 5 YSM versus 11-20 YSM groups (P = 0.007) and in the < 5 YSM versus > 20 YSM
      groups (P < 0.0001). The T score of BMDCorti by YSM differed significantly only
      between the < 5 YSM versus 11-20 YSM groups (P < 0.0001) and between the 11-20
      YSM and > 20 YSM groups (P < 0.005). CONCLUSION: In contrast with what has been
      postulated in recent studies, our results showed that postmenopausal bone loss
      was similar in the cortical and trabecular bone compartments in the first 20
      years after menopause. Trabecular bone loss was greater than cortical bone loss
      in late menopause (> 20 years).

PMID- 9651908
TI  - Are menopausal symptoms associated with bone mineral density and changes in bone
      mineral density in premenopausal women?
AB  - BACKGROUND: The relationship between menopausal symptoms and bone mineral density
      (BMD) was examined in 290 premenopausal women, ages 44-50 years, participating in
      a randomized clinical trial of a dietary and exercise intervention: The Women's
      Healthy Lifestyle Project. METHODS: Information on hot flashes (presence,
      absence), menstrual cycles (irregular, regular) and menstrual flow per period
      (variable, same) over the past 6 months was collected at entry. Participants
      reporting at least one menopausal symptom were classified as symptomatic and
      compared to those having no symptoms. Bone mineral density (BMD) at the lumbar
      spine (L1-L4), total hip and whole-body were made at baseline and at 30 months
      using a dual-energy X-ray absorptiometer (Hologic QDR 2000 densitometer).
      RESULTS: Baseline BMD at the spine, hip and whole-body were significantly reduced
      in women reporting menopausal symptoms compared to asymptomatic women, after
      adjustment for age, weight and intervention status (all p < 0.05). Women with
      irregular menstrual cycles had greater annualized rates of bone loss at the spine
      and hip than asymptomatic women (spine, -0.77 (1.6)% per year vs. -0.19 (1.0)%
      per year, p = 0.0043; hip, -0.37 (1.1)% per year vs. -0.04 (1.0)% per year, p =
      0.061), after adjustments for age, percent change in weight, intervention status,
      and baseline BMD. Similar findings were not found for whole-body BMD.
      CONCLUSIONS: These results suggest that menopausal symptoms are useful for the
      effective identification of premenopausal women at higher risk of low BMD and
      perhaps, of osteoporosis.

PMID- 9651909
TI  - Comparison of the transdermal delivery of estradiol from two gel formulations.
AB  - OBJECTIVE: Conventional oral oestrogen replacement therapy can relieve
      postmenopausal symptoms but is associated with undesirable side-effects which can
      be minimised by avoiding the fluctuating hormonal blood levels resulting from
      oral therapy and eliminating hepatic first-pass metabolism by the use of the
      transdermal route. The two commercially available transdermal gel formulations
      differ in composition and application recommendations. Sandrena Gel contains 0.1%
      (w/w) and Oestrogel 0.06% (w/w) estradiol and recommended dosages are 0.5-1.5 g
      over 200-400 cm2 (Sandrena Gel) and 2.5 g gel over 720 cm2 (Oestrogel). In
      transdermal therapy the formulation composition may have a significant effect on
      drug delivery and we have therefore compared the permeation of estradiol from
      these formulations across human skin in vitro. METHODS: The in vitro percutaneous
      penetration of estradiol from the formulations through epidermal membranes
      prepared from excised female human thing skin was assessed over a 24 h period
      using static type Franz diffusion cells. RESULTS: Permeation of the active was
      similar from each formulation representing (at 24 h) 18.2 +/- 3.5% of the applied
      dose from Sandrena Gel and 17.4 +/- 4.8% of the applied dose from Oestrogel.
      These percentages equate to cumulative skin permeations of 0.65 +/- 0.15
      microgram/cm2 and 0.45 +/- 0.15 microgram/cm2 respectively. CONCLUSION: The
      results suggest that the two formulations are bioequivalent at the recommended
      dose levels.

PMID- 9651910
TI  - Image-guided neurosurgery comparing a pointer device system with a navigating
      microscope: a retrospective analysis of 208 cases.
AB  - A retrospective analysis of neuronavigation procedures performed at the Vienna
      Neurosurgical Clinic was undertaken to elucidate the advantages of 2 technically
      different navigation systems in clinical use. In a 30-month period, 208 frameless
      stereotactic procedures were performed using a stereotactic microscope (MKM
      System, Zeiss; 92 procedures in 87 patients; 47 female, 40 male; mean age, 46
      yrs) and a light emitting diode (LED) based pointer navigation device (Easy Guide
      Neuro (EGN), Philips; 116 procedures in 114 patients; 63 female, 51 male; mean
      age 46.4 yrs). The navigating microscope was exclusively used for cranial
      navigation, the pointer device system in 107 cases for cranial and in 9 cases for
      spinal navigation. Procedures were CCT-guided in 109 cases, MRI-guided in 95, and
      both CT/MRI guided in 4 cases. Skin fiducials were used in all these procedures.
      The MKM system provided coordinate-based navigation, similar to frame systems.
      This allowed surgical planning and performance using stereotactic coordinates for
      target calculation. Additionally, tumor volumes were defined by contours and
      projected into the ocular of the microscope, allowing guidance during targeting
      and resection of lesions. Both of these features proved beneficial in tumor
      surgery (60.8% MKM cases), cavernoma surgery (21.8% MKM cases), and epilepsy
      surgery (14.1% MKM cases). In contrast to the microscope, the pointer navigation
      system could be employed for intuitive correlation of image points with points of
      interest in the operating field by using a LED-equipped pointer device. This
      permitted image guidance during a wide spectrum of neurosurgical procedures, in
      tumor surgery (68.1% EGN cases), cavernoma surgery (5.1% EGN cases), epilepsy
      surgery (14.1% EGN cases), vascular surgery (3.4% EGN cases), spinal surgery
      (7.8% EGN cases), and guidance for burr holes and drainages (6.9% EGN cases),
      without calculating stereotactic coordinates. This analysis showed clear
      differences in the application of the two systems and may facilitate the decision
      as to which system best meets the individual demands of a neurosurgical
      department.

PMID- 9651911
TI  - MiniMATCH: a simple method for local data transfer between MRI and CT scan sets.
AB  - A comparison of the spatial position of distinct locations within cranial MRI and
      CT scan sets can easily be done with a simple algorithm designed as a computer
      program. After determination of a basic system formed by the coordinates of
      anatomical landmarks in CT and MRI, arbitrary points can be identified on one
      scan set and transferred quantitatively to the other. Pros and cons of the method
      are discussed and opposed to the properties of specifically designed image
      processing systems.

PMID- 9651912
TI  - Control of hemorrhage during AVM surgery--with special reference to treatment of
      dilated capillaries and arteries around the nidus.
AB  - Control of hemorrhage during AVM surgery is one of the key issues to prevent
      NPPB. Inadequate procedures for hemostasis of feeders and drainers, so-called
      dilated capillaries and arteries (moja moja blood vessels) that are located on
      the side facing the normal brain, and inappropriate surgical strategies for
      intraoperative hemorrhage from these blood vessels are frequently the main cause
      of the difficulty in achieving hemostatic control. We conclude that it is
      important to aggressively reduce the occurrence of intraoperative hemorrhage and
      prevent or minimize the dilatation of abnormal capillaries and arteries due to
      inappropriate surgical procedures on the basis of the fundamental surgical
      strategy, i.e., feeder-->nidus-->drainer. Adequately securing the length and
      adequate coagulation of hemorrhagic blood vessel, employing a skillful bipolar
      coagulator technique aimed at controlling intraluminal pressure and blood flow on
      the central side, are believed to be key factors in hemorrhage treatment.

PMID- 9651913
TI  - Endoscopic endonasal transsphenoidal approach to the sella: towards functional
      endoscopic pituitary surgery (FEPS).
AB  - Standard microscopical transsphenoidal surgery is used world-wide in most sellar
      lesions, but continuing technological progress leaves room for further
      possibilities. The authors have employed a slightly modified Jho-Carrau technique
      for endoscopic endonasal transsphenoidal removal of pituitary lesions. This
      approach has been successfully used in 15 consecutive patients; the preliminary
      results are reported. The advantages and the limitations of this technique are
      discussed and compared to standard transsphenoidal surgery. In consideration of
      the low invasiveness of this approach and of the improved respect for the inner
      nose and sinus structures, the authors suggest the new term of Functional
      Endoscopic Pituitary Surgery (FEPS) to characterize this simple one-nostril
      endoscopic endonasal procedure.

PMID- 9651914
TI  - Endoscopic neurosurgery: report of the first five cases done in Malaysia using
      the Caemaert-Abdullah method.
AB  - The first endoscopic procedure done in Malaysia using the Caemaert-Abdullah
      method is reported and the followup results showed an excellent neurosurgical
      outcome. A 16-year-old girl with an aqueduct stenosis was operated on using a
      free-hand, computer-assisted endoscopic method where a third ventriculostomy was
      done. This was the first case being carried out in the Hospital Universiti Sains
      Malaysia. The next two cases were a suprasellar pituitary cyst in an elderly man
      and a child with an obstructive hydrocephalus who was previously shunted which
      became infected. Both endoscopic procedures, extirpation of the cyst using a
      Nd:Yag laser and a third ventriculostomy, respectively, were done under general
      anaesthesia in the supine position. Follow-up revealed a transient diabetes
      insipidus in all three cases up to 48 hours after the operation which resolved
      spontaneously. The fourth case involved an endoscopic removal of retained
      ventricular catheter after rectal migration of a shunt in an eight-year-old girl
      with congenital hydrocephalus. The fifth was a free-hand endoscopy with
      perforation of multiple brain septae in a ten-month-old baby with hydrocephalus
      secondary to meningitis. The final outcomes for all the cases were favourable
      hence we conclude that endoscopic neurosurgery is a safe procedure and hope that
      more neurosurgeons will continue to use this method, especially for the
      management of intraventricular cyst and hydrocephalus and especially in South
      East Asia.

PMID- 9651915
TI  - A malleable endoscopic suction instrument: technical note.
AB  - Flexible endoscopes are being employed for a variety of neurosurgical procedures.
      These instruments have drawbacks, especially in their ability to evacuate clotted
      blood. We have attempted to rethink the design of these instruments and have
      developed a malleable endoscopic suction instrument. This has proved to be
      helpful in a variety of intracranial and intraspinal procedures.

PMID- 9651916
TI  - Intracranial aneurysms: a review of endovascular and surgical treatment in 248
      patients.
AB  - We reviewed the medium-term results of endovascular treatment of intracranial
      aneurysms and compared patient selection and results with those of open surgery.
      Between January 1992 and December 1995, a total of 248 consecutive patients were
      treated for 297 aneurysms (61 unruptured and 236 ruptured). 162 aneurysms in 142
      patients (mean age, 48.5 years) were treated microsurgically and 134 aneurysms in
      106 patients (mean age, 54.2 years) were treated by endovascular embolization
      with Guglielmi detachable coils (GDC). The mean follow-up was 2.6 years (range,
      1.5 to 4.5 years). There was no significant difference in patient population and
      selection in terms of age, sex or location of aneurysms between both methods.
      Both modalities achieved excellent results (defined as no neurological deficit)
      in patients with unruptured aneurysms and with no or minor deficits after
      subarachnoid hemorrhage (SAH) between 71% and 88%. Patients with moderate
      deficits after SAH had excellent outcomes in 49% after open surgery, and 47%
      after embolization. Poor grade patients had, equally, as well an acceptable as a
      pour outcome, between 0% and 50%. There was no significant difference between the
      outcome of surgical or endovascular patients. We conclude that GDC embolization
      is not associated with a higher risk of morbidity and mortality than open
      surgery. This risk may even be lower for lesions in surgically unfavorable
      locations. The GDC technique is a less invasive, effective option to prevent re
      bleeding in early stage, even in poor-grade patients. However, these encouraging
      medium-term results have to be confirmed by a longer observation period.

PMID- 9651917
TI  - Conservative management of acoustic neurinomas: prospective study of long-term
      changes in tumor volume and auditory function.
AB  - Recently reported retrospective analysis on the natural courses of acoustic
      neurinomas have disclosed that 26-86% of tumors show very slow, or no, growth for
      many years. To our knowledge, however, there have been no prospective analyses of
      the natural course of these tumors. We prospectively analyzed tumor growth as
      well as auditory function changes in 12 patients (13 tumors) managed
      conservatively. All 12 patients were advised to undergo both pure tone audiometry
      and magnetic resonance imaging at 3-4 month intervals for the first follow-up
      year and at 1-2 year intervals thereafter. Then, in the event of either
      significant tumor growth (> 20% volume increase) or hearing deterioration (> 10
      dB), a decision would be made as to whether the patient should undergo either
      surgery or radiosurgery. A significant increase in tumor volume was confirmed in
      seven of the 13 tumors during the mean observation period of 564 days (88-1269
      days). In another patient, though neither tumor growth nor worsening of auditory
      acuity was significant, the patient complained of subjective change in the
      symptoms. Therefore, we decided to treat eight (62%) of the 13 tumors. In
      contrast, neither tumor growth nor worsening of auditory acuity has as yet
      occurred in the remaining five tumors (38%) which have been observed for a mean
      period of 627 days (342-1377 days). Careful follow-up of these five patients is
      ongoing. Although further long-term follow-up is clearly necessary, conservative
      treatment appears to be a reasonable alternative to immediate treatment for
      selected patients with acoustic neurinomas.

PMID- 9651918
TI  - Coronally oriented vertical fracture of the axis body: surgical treatment of a
      rare condition.
AB  - The neurosurgical management in a rare case of vertical axis fracture is
      presented along with discussion of the supposed pathogenetic mechanisms and the
      biomechanics underlying this type of cervical spine injury. Comprehensive
      neuroradiological investigation prior to surgery clearly demonstrated the
      dislocation of the anterior part of the axis body with concomitant C 2/C 3-disk
      injury. Therefore, the unstable fracture had to be managed by a one-time combined
      ventrodorsal approach using anterior C 2-C 3 locking plate fusion and C 2
      bilateral dorsal transpedicular screw fixation. No operative morbidity resulted
      from this procedure, and stable bony fusion was achieved with minimal restriction
      of head mobility and with minor residual complaints. This case illustrates the
      variable biomechanical response of the upper cervical spine to trauma and the
      advantages of a non-standard surgical approach for internal fixation of the
      injured cervical spine.

PMID- 9651919
TI  - Foot drop following brain tumors: case reports.
AB  - Three cases with foot drop following brain tumors in patients suffering from
      parasagittal pathology are reported. Foot drop was the first complaint in the
      patients in our series. We generally notice foot drop as a sign of lumbar disc
      herniation or peroneal nerve lesions but rarely foot drop may also occur with
      brain lesions.

PMID- 9651920
TI  - Mirror movements associated with cervical meningocele: case report.
AB  - A patient with mirror movements associated with cervical meningocele has been
      presented in this report. The MRI showed normal cerebrum and cervical
      meningocele, and an anomaly at the posterior to the cervical spinal cord-medulla
      junction. Unilateral transcranial magnetic stimulation evoked bilateral responses
      at similar latencies on the thenar muscles which are quite different from those
      observed in normal subjects. This case adds another etiological cause to the
      mirror movements.

PMID- 9651921
TI  - The relative contribution of antibody production and CD8+ T cell function to
      immune control of Trypanosoma cruzi.
AB  - The life cycle of the protozoan parasite Trypanosoma cruzi in mammalian hosts
      includes both non-dividing trypomastigote forms which circulate in the blood and
      replicating intracellular amastigotes which reside within the cytoplasm of a
      variety of host cells. In this study we have used mice with induced mutations in
      genes responsible for either antibody production or cytolytic T lymphocyte (CTL)
      function to examine the relative contributions of these effector mechanisms to
      control of T. cruzi. Mice deficient in the production of antibodies exhibited a
      delay in the rise in acute phase parasitaemia and an extended time to death
      relative to mice lacking CD8+ T cells. Nevertheless, B cell deficient mice
      eventually succumbed to the infection. Prior infection with an avirulent strain
      of T. cruzi failed to protect either CD8+ T cell-deficient mice or B cell
      deficient mice from challenge infection with virulent parasites. In contrast,
      mice with disruptions in the genes controlling perforin- or granzyme B-mediated
      cytolytic pathways had parasitaemia and mortality rates similar to wild-type mice
      and were protected from secondary infection by prior exposure to avirulent
      parasites. These results 1) confirm that antibody production, although secondary
      in importance to cellular responses, is nevertheless absolutely required and 2)
      perforin- or granzyme B-mediated lytic pathways are not required for control of
      T. cruzi infection.

PMID- 9651922
TI  - The immune response and immunopathology in infection with Schistosoma mansoni: a
      key role of major egg antigen Sm-p40.
AB  - The immune response and related granulomatous inflammation in infection with
      Schistosoma mansoni are ultimately dependent on SEA-sensitized CD4+ Th cells and
      comprise multiple pathways variously involving the activation and recruitment of
      different cell populations and the production of different inflammatory
      cytokines, all under the influence of regulatory genetic factors. The spontaneous
      downregulation of granuloma formation (immunomodulation), in turn, is a well
      known phenomenon, but the full extent of its precipitating factors is still
      uncertain. This review describes a pathway leading to immunomodulation that
      features at its centre the down-regulatory cytokine IL-10. This mechanism is
      attractive because it offers a cogent correlation between findings in the
      laboratory and those displayed by patients affected with the disease. The Sm-p40
      antigen, a major component of schistosome eggs, elicits a strong CD4+ Th cell
      response in H-2k mice that correlates with intense granuloma formation; in
      contrast, its immunogenicity is relatively minor during infection of other mouse
      strains that develop smaller granulomas. Of great interest is that the Sm-p40
      antigen only elicits a Th-1 type cytokine response, a phenotype that remains
      constant even as the overall response to SEA shifts to a Th-2 type. The Sm-p40
      molecule has a dominant epitope that is the target of CD4+ Th cells from infected
      H-2k mice; indeed, a minimal peptide that bears the epitope binds to I-Ak. The
      importance of pursuing a systematic elucidation of the major egg antigens,
      resides in the exciting possibility of specifically desensitizing the CD4+ Th
      cells that mediate granuloma formation, which may achieve meaningful prevention
      or amelioration of clinical disease.

PMID- 9651923
TI  - Setting in motion the immune mechanisms underlying genetically determined
      resistance and susceptibility to infection with Leishmania major.
AB  - The murine model of infection with Leishmania major has allowed the demonstration
      of a causal relationship between, on the one hand, genetically determined
      resistance to infection and the development of a Th1 CD4+ cell response, and on
      the other hand, genetically determined susceptibility and Th2 cell maturation.
      Using this murine model of infection, the role of cytokines in directing the
      functional differentiation pathway of CD4+ T cell precursors, has been
      demonstrated in vivo. Thus, IL-12 and IFN-gamma have been shown to favour Th1
      cell development and IL-4 is crucial for the differentiation of Th2 responses.
      Maturation of a Th2 response in susceptible BALB/c mice following infection with
      L. major is triggered by the IL-4 produced during the first two days after
      parasite inoculation. This IL-4 rapidly renders parasite specific CD4+ T cells
      precursors unresponsive to IL-12. A restricted population of CD4+ T cells
      expressing the V beta 4V alpha 8 TCR heterodimer and recognizing a single epitope
      on the LACK (Leishmania Activated C-Kinase) antigen of L. major is responsible
      for this rapid production of IL-4, instructing subsequent differentiation towards
      the Th2 phenotype of CD4+ T cells specific for several parasite antigens.

PMID- 9651924
TI  - A protective role for IL-6 during early infection with Toxoplasma gondii.
AB  - IL-6 deficient mice were found to be significantly more susceptible to peroral
      infection with Toxoplasma gondii than their wild-type counterparts as measured by
      survival, brain cyst burdens and brain pathology at 28 days post infection. The
      physical manifestations of disease, such as weight loss, were not observed in IL
      6 deficient animals until at least seven days later than such changes occurred in
      wildtype mice. During this early stage of infection IL-6+/+ but not IL-6-/- mice
      mounted a peripheral blood neutrophilia. Furthermore, between 6-8 days post
      infection there was a significant increase in plasma IFN-gamma levels in wild
      type but not IL-6 deficient mice. Not until days 18-23 post-infection, concurrent
      with the majority of deaths in IL-6-/- mice, were plasma IFN-gamma levels
      substantially and significantly raised in IL-6-/- mice. At this time not only
      were these plasma IFN-gamma levels 20-fold higher than background but eight-fold
      greater than peak (6-8 days post-infection) IFN-gamma levels in IL-6+/+ mice. IFN
      gamma dependent parasite specific IgG2a levels were also significantly higher in
      IL-6-/- mice over this period and thereafter. Overall the evidence suggests that
      in the absence of IL-6 mice are unable to initiate a rapid proinflammatory
      response against T. gondii, which allows increased parasite growth. Increased
      mortality in IL-6-/- mice may be directly due to this increased parasite burden
      and the excessive inflammatory response this induces three weeks post-infection.

PMID- 9651925
TI  - Profound suppression of cellular proliferation mediated by the secretions of
      nematodes.
AB  - Loss of T lymphocyte proliferation and the emergence of a host response that is
      dominated by a Th2-type profile are well-established features of human filarial
      infection. Down-regulation and modulation of host T cell responses during
      lymphatic filariasis has been investigated by implantation of parasite stages
      into inbred mice. Adherent peritoneal exudate cells (PEC) from mice transplanted
      with adult or larval Brugia malayi parasites are profoundly anti-proliferative
      but do not prevent antigen-specific cytokine production by T cells. We
      demonstrate here that the excretory/secretory (E/S) products of the adult
      parasite are sufficient to induce PEC that block proliferation if injected daily
      into mice. We have previously shown that in vivo production of host IL-4 is
      required for the generation of suppressive cells. Because the induction of host
      IL-4 is characteristic of infection with nematodes, we asked whether E/S from two
      other nematode parasites, Nippostrongylus braziliensis and Toxocara canis were
      also capable of generating a suppressor cell population. Injection of E/S from
      these two parasites also led to a reduction in T cell proliferation suggesting
      that this mechanism of down-regulating host responses is a feature common to
      nematode parasites.

PMID- 9651926
TI  - The effect of nematode infection upon intestinal smooth muscle function.
AB  - Nematode infections are useful in studying both host defence and inflammation
      induced changes in intestinal physiology, including increased contraction by
      intestinal muscle. Our initial studies of the heightened muscle function found
      during T. spiralis infection led to investigations of the role of immune and
      inflammatory cells and mediators in the immunodulation of intestinal muscle
      function. By infecting various immunodeficient mouse strains, as well as gene
      transfer to the intestine, T lymphocytes, and in particular the CD4+ve subset
      were found to be responsible for altering smooth muscle function. However,
      eosinophils as well as the cytokine interleukin-4 may also be involved.
      Investigations also indicate a potential role for increased muscle function and
      propulsive activity in expelling nematode parasites. Mutant mice which suffer
      aberrant intestinal propulsion, or based upon an immunodeficiency, undergo
      reduced changes in muscle function during infection, undergo prolonged
      infections. While increased muscle function may be an adaptive host response, the
      changes in muscle function may persist long after the resolution of the
      infection. Thus understanding the mechanisms behind the immunomodulation of
      intestinal muscle function may also impact upon clinical gastroenterology, since
      motility disturbances in man often occur following enteric infections, or other
      inflammatory conditions of the bowel.

PMID- 9651927
TI  - Role of neutrophils in innate resistance to Entamoeba histolytica liver infection
      in mice.
AB  - In order to define the role of neutrophils in the innate resistance to Entamoeba
      histolytica liver infection in mice, we examined the pattern of liver lesion
      induced by direct injection of E. histolytica trophzoites in normal mice and in
      neutrophil-depleted mice. A variety of histological lesions were found, the
      extent of liver damage was considerably higher in the neutrophil-depleted mice.
      Livers from neutrophil-depleted mice displayed areas of liquefactive (lytic)
      necrosis containing a large number of amoebae and absence of neutrophils or
      mononuclear cells. By contrast, in the liver of normal mice, neutrophils were
      seen associated to E. histolytica at early stages of infection. In both mouse
      groups, areas of TUNEL-positive dead hepatocytes were observed and a
      characteristic internucleosomal banding pattern of genomic DNA consistent with
      apoptosis was detected in DNA harvested from amoebic liver lesions. These data
      suggest that neutrophils play an important role in the mechanisms of resistance
      to amoebic liver infection in mice. In addition, our histological analysis
      suggests that E. histolytica is capable of producing liver damage in the absence
      of inflammatory cells.

PMID- 9651929
TI  - Intestinal mast cell response and mucosal defence against Strongyloides
      venezuelensis in interleukin-3-hyporesponsive mice.
AB  - Recently several inbred strains of mice were found to be hyporesponsive to
      Interleukin (IL)-3 because of a 5-bp deletion in the intron 7 of the gene that
      encodes IL-3 receptor alpha subunit (IL-3R alpha). Due to this mutation, mast
      cells were not generated in vitro from bone marrow cells of these mice under the
      presence of IL-3. Intestinal mucosal mast cells, of which growth/differentiation
      is dependent on IL-3, are important effector cells in immune-mediated expulsion
      of intestinal nematodes, Stronglyoides spp. In the present study, therefore, we
      examined intestinal mast cell response and mucosal defence against Strongyloides
      venezuelensis in IL-3-hyporesponsive C58/J and A/J mice. After subcutaneous
      inoculation with 10,000 infective larvae, C58/J and IL-3-responsive C57BL/6 mice
      showed identical kinetic patterns of daily faecal egg output and intestinal mast
      cell response. When these mice were infected with 3000 L3 and, five weeks later,
      they were challenged by intraduodenal implantation of 800 S. venezuelensis adult
      worms, the timing of logarithmic decline of faecal egg count as well as
      intestinal mastocytosis was delayed for two days in C58/J mice. Kinetics of
      intestinal mastocytosis and faecal egg excretion after a primary and challenge
      infection in A/J mice, another IL-3-hyporesponsive strain, were identical with
      those seen in C58/J mice. These results suggest that intestinal mast cell
      response and mucosal defence against S. venezuelensis of the mutant mice were
      almost completely compensated in vivo. Possible mechanisms of induction of
      intestinal mast cell response in IL-3R alpha-defective mice are discussed.

PMID- 9651928
TI  - Definition of T cell epitopes within the 19 kDa carboxylterminal fragment of
      Plasmodium yoelii merozoite surface protein 1 (MSP1(19)) and their role in
      immunity to malaria.
AB  - MSP1(19) is one of the leading malaria vaccine candidates. However, the mechanism
      of protection is not clear. To determine whether MSP1(19)-specific effector T
      cells can control parasitaemia, we analysed the specificity of T cells induced
      following immunization with recombinant forms of P. yoelii MSP1(19) and asked
      whether they could protect mice. There was no evidence that effector T cells were
      capable of protecting since: (1) immunization of mice with yMSP1(19), but not
      defined epitopes, was able to induce protection; and (2) long term MSP1(19)
      specific CD4+ T cell lines were incapable of adoptively transferring protection.
      In contrast, priming mice with the T cell epitopes resulted in a rapid anamnestic
      antibody response to MSP1(19) after either challenge with MSP1(19) or parasite.
      Thus, MSP1(19) contains multiple T cell epitopes but such epitopes are the
      targets of helper T cells for antibody response but not of identified effector T
      cells capable of controlling parasitaemia.

PMID- 9651930
TI  - Protection of Fasciola hepatica in the gut mucosa of immune rats is associated
      with infiltrates of eosinophils, IgG1 and IgG2a antibodies around the parasites.
AB  - We investigated the immune effector mechanisms that underlie protection against
      F. hepatica in the gut wall of immune rats, using (immuno)histochemistry. In the
      lamina propria of immune Wistar rats, four weeks after oral infection,
      frequencies of IgE-positive cells, eosinophils and mucosal mast cells were
      significantly increased, compared with naive rats. These factors represent the
      traditional effector mechanisms against helminths. No significant differences
      were detected between the two groups in frequencies of IgM-, IgG2a-, IgG1- and
      IgA- positive cells, CD4- and CD8-positive cells, NK cells, macrophages,
      neutrophils or goblet cells. Upon challenge of immune rats with F. hepatica in an
      ex vivo gut segment, NEJs that migrated through the (sub)mucosa were coated with
      IgG1 and IgG2a antibodies and surrounded by eosinophils. No IgE or IgA antibodies
      were detected on the parasites. The onset of these immune effector responses, two
      h after challenge, was related to the expression of protection. These results
      suggest that NEJs are killed by an eosinophil-mediated cytotoxic response
      involving IgG antibodies. These antibodies were not produced in the intestine,
      but infiltrated the gut upon challenge. The observed immune effector responses
      were not restricted to the site where the primary infection is located, namely
      the small intestine, but were also detected in the large intestine. The presence
      of the protective immune mechanisms in two other rat strains demonstrates the
      pivotal importance of these responses, irrespective the genetic background of the
      host.

PMID- 9651931
TI  - Immunoregulation in experimental murine Trypanosoma congolense infection: anti-IL
      10 antibodies reverse trypanosome-mediated suppression of lymphocyte
      proliferation in vitro and moderately prolong the lifespan of genetically
      susceptible BALB/c mice.
AB  - We infected highly susceptible BALB/c and relatively resistant C57BL/6 mice with
      cloned Trypanosoma congolense and followed the effects of these infections on the
      circulating parasite numbers, mouse mortality and cytokine expression. C57BL/6
      mice controlled their parasitaemia and survived for up to 163 +/- 12 days, while
      BALB/c mice could not control their parasitaemia and succumbed to the infection
      within 8.4 +/- 0.5 days. Susceptible BALB/c mice had dramatically higher plasma
      levels of IL-10 than the resistant C57BL/6 mice from day 7 forward. This was
      preceded by an earlier and higher level induction of splenic IL-10 messenger RNA
      (mRNA) expression in the infected BALB/c mice. There was a strong negative
      correlation between the splenocyte proliferative responses to Concanavalin-A (Con
      A) and their production of IL-10 in these infected BALB/c mice. Co-treatment of
      the Con-A-stimulated spleen cell cultures with monoclonal anti-IL-10 antibodies,
      but not isotype-matched control antibodies, could completely reverse this
      suppression of the splenocyte proliferative response. Finally, in three
      experiments, anti-IL-10 antibody treatment in vivo reduced the peak circulating
      parasitaemia of infected BALB/c mice by 43% and increased their median survival
      periods by 38% relative to isotype-matched control antibody-treated mice.

PMID- 9651932
TI  - Seasonal changes in the Plasmodium falciparum population in individuals and their
      relationship to clinical malaria: a longitudinal study in a Sudanese village.
AB  - Residents of Daraweesh village in Sudan were monitored for Plasmodium falciparum
      infection and malaria morbidity in 3 malaria seasons from 1993 to 1996. Malaria
      parasites were detected microscopically and by polymerase chain reaction (PCR) in
      a series of cross-sectional surveys. PCR revealed submicroscopical infections
      during the dry season, particularly among individuals who had recovered from a
      malaria episode following successful drug treatment. Clinical and subclinical
      infections were contrasted by assaying for allelic polymorphism at 2 gene loci,
      MSP-1 and GLURP and 2 hypotheses examined with reference to these data: that
      clinical malaria is associated with infection with novel parasite genotypes not
      previously detected in that host, or alternatively, that clinical malaria
      episodes are associated with an increased number of clones in an infection. We
      detected more mixed infections among clinical isolates, but people carrying
      parasites during the dry season were not found to have an increased risk of
      disease in the following malaria season. There was a clear association of disease
      with the appearance of novel parasite genotypes.

PMID- 9651933
TI  - Formation of basement membrane-like structure terminates the cellular
      encapsulation of microfilariae in the haemocoel of Anopheles quadrimaculatus.
AB  - The encapsulation of microfilariae in the haemocoels of mosquitoes combines both
      humoral and cellular reactions: the microfilariae are first encased in an
      acellular layer of melanin, followed by a cellular encapsulation by
      plasmatocytes. In this study, we demonstrated that cellular encapsulation of
      Brugia pahangi microfilariae in the haemocoel of the mosquito Anopheles
      quadrimaculatus was terminated by the formation of a basement membrane-like
      structure on the outermost surface of the cellular capsule. This structure
      occurred in the early stage of cellular encapsulation and was evident on the
      exterior surface of the plasmatocyte, when the active haemocytes were attaching
      to the already melanized microfilariae. The termination structure appears to be
      laid down by releasing the vesicle inclusions of haemocytes and has similarities
      in ultrastructure and cationic colloidal gold staining properties with that of
      mosquito basement membranes.

PMID- 9651934
TI  - Effect of praziquantel treatment on experimental porcine Schistosoma japonicum
      infection.
AB  - The aims of the study were to assess the effect of praziquantel on Schistosoma
      japonicum infection in pigs, and to elucidate the level of resistance to
      reinfection after treatment. Pigs were given a single infection with S. japonicum
      followed by a praziquantel treatment (40 mg/kg) week 8, reinfection week 12 and
      perfusion week 20 post-primary infection. Relevant control groups were included.
      Worm burdens, faecal and tissue egg counts, gross- and histopathology of the
      liver and specific liver enzymes were assessed. The results showed a 100% cure
      rate of praziquantel against S. japonicum in pigs. Worm nodules were present in
      equal numbers in the intestinal wall 4 and 14 weeks post-treatment. Treatment did
      not significantly reduce the number of tissue eggs neither 4 nor 14 weeks post
      treatment. No worm nodules or worm-induced lesions were found in the livers of
      the treated pigs and the levels of liver enzymes were comparable in treated and
      nontreated infected pigs. Periportal and septal fibrosis regressed following
      treatment. Faecal egg counts were significantly reduced 2 (56%) and 4 (82%) weeks
      after treatment. Challenge infection 4 weeks post-treatment did not result in
      establishment of new worm pairs. Praziquantel proved to be highly effective
      against S. japonicum in pigs without causing pathological side-effects in the
      liver.

PMID- 9651935
TI  - Isolation of an aspartic proteinase precursor from the egg of a hard tick,
      Boophilus microplus.
AB  - An aspartic proteinase precursor, herein named BYC (Boophilus Yolk pro-Cathepsin)
      was isolated from eggs of the hard tick, Boophilus microplus. As judged by
      electrophoresis on sodium dodecyl sulfate polyacrylamide slab gel (SDS-PAGE),
      purified BYC presented 2 bands of 54 and 49 kDa, bearing the same NH2-terminal
      amino acid sequence. By Western blot analysis, BYC was also found in the
      haemolymph, indicating an extraovarian site of synthesis. Several organs were
      incubated in culture medium with [35S]methionine, and only the gut and fat body
      showed synthesis of BYC polypeptides. Protein sequencing of both the NH2-terminal
      and an internal sequence obtained after cyanogen bromide (CNBr) cleavage of BYC
      revealed homology with several aspartic proteinase precursors. Incubation at pH
      3.5 resulted in autoproteolysis of BYC, which produced the mature form of the
      enzyme, that displayed pepstatin-sensitive hydrolytic activity against
      haemoglobin. Western blot analysis using anti-BYC monoclonal antibodies showed
      proteolytic processing of BYC during embryogenesis and suggested activation of
      the enzyme during development. A role of BYC in degradation of vitellin, the
      major yolk protein of tick eggs, is discussed.

PMID- 9651936
TI  - Tick salivary gland extracts promote virus growth in vitro.
AB  - Saliva of blood-feeding arthropods promotes infection by the vector-borne
      pathogens they transmit. To investigate this phenomenon in vitro, cultures of
      mouse L cells were treated with a salivary gland extract (SGE) prepared from
      feeding ticks and then infected with vesicular stomatitis virus (VSV). At low
      input doses of VSV, viral yield was increased 100-fold to 10,000-fold by 16-23 h
      post-infection compared with untreated cultures, and depending on the SGE
      concentration. SGE-mediated acceleration of viral yield corresponded with the
      earlier appearance of VSV nucleocapsid protein as detected by 2-dimensional
      electrophoresis of infected cells. The observation that physiological doses of
      virus (i.e. doses likely to be inoculated by an infected arthropod vector into
      its vertebrate host during blood-feeding) respond to SGE treatment in vitro
      provides a new opportunity for identifying the factors in tick saliva that
      promote virus transmission in vivo.

PMID- 9651937
TI  - Vector competence of 7 rhipicephalid tick stocks in transmitting 2 Theileria
      parva parasite stocks from Kenya and Zimbabwe.
AB  - The competence of 7 different stocks of Rhipicephalus appendiculatus and R.
      zambeziensis to transmit 2 different stocks of Theileria parva was compared by
      feeding nymphae of each tick stock simultaneously on infected cattle and
      assessing the infections in the salivary glands of the resultant adult ticks.
      There were significant differences in the patterns of infection of the 2 stocks
      (T. parva Muguga and T. parva Boleni) in the different stocks of ticks, and these
      differences were shown to be reproducible. The Muguga tick stock from Kenya and
      the Zambia tick stock from Eastern Province had the highest infections of T.
      parva Muguga and T. parva Boleni respectively. The Zambia Southern Province tick
      stock and the Zimbabwe Mashonaland West tick stock had the lowest infections of
      T. parva Muguga and T. parva Boleni respectively. The difference in mean
      abundance of infection between the most and least efficient vector for T. parva
      Muguga was 63.3 while that for T. parva Boleni was 54.4 infected acini. The
      implications of these results for laboratory transmission of T. parva and for the
      epidemiology of theileriosis are discussed.

PMID- 9651938
TI  - Characterization of trypanosome infections by polymerase chain reaction (PCR)
      amplification in wild tsetse flies in Cameroon.
AB  - The polymerase chain reaction (PCR) method was used to characterize trypanosome
      infections in tsetse flies from 3 sleeping sickness foci in Cameroon. The
      predominant tsetse species found was Glossina palpalis palpalis. An average
      infection rate of 12.1% was revealed by microscopical examination of 888 non
      teneral tsets flies. PCR amplification analyses for trypanosome identification
      were carried out on 467 flies, with primer sets specific for Trypanosoma
      (Trypanozoon) brucei s.1., T. (Duttonella) vivax, T. (Nannomonas) simiae and
      forest type T. (Nannomonas) congolense. Of 467 flies 93 were positive by
      microscopical analysis while PCR succeeded in identifying 89 positive flies. Of
      the PCR-positive flies 34 (38.2%) were negative by microscopical examination. PCR
      amplification, when compared to the parasitological technique, gave a higher
      estimate of infection rate of trypanosomes in natural tsetse populations. The PCR
      technique did, however, fail to identify 40.9% (38/93) of the parasitologically
      positive flies. The reasons for this failure are discussed. The overall
      prevalence of mixed infections, assessed by PCR, was 37.1%; the majority (72.7%)
      involved T. brucei and forest type T. congolense.

PMID- 9651939
TI  - Observations on the mechanism of eggshell formation in the liver fluke, Fasciola
      hepatica.
AB  - A mechanism for eggshell production in Schistosoma mansoni has been proposed
      (Wells & Cordingley, 1991), and suggests that the release of eggshell protein
      globules from the vitelline cells occurs under alkaline conditions within the
      ootype followed by their subsequent fusion to form the eggshell. Fusion and
      tanning of these components produces eggshell which autofluoresces. The present
      study was carried out to determine whether a similar process operates in Fasciola
      hepatica. A number of drug treatments were used to disrupt key steps in the
      maturation of vitelline cells. Treatment with the calcium ionophore lasalocid (1
      x 10(-5) M) led to the premature release of eggshell globules from the vitelline
      cells but not their fusion. Incubation in monensin (1 x 10(-6)M), a sodium
      ionophore and ammonium chloride (NH4Cl) (5 x 10(-2) M), a weak base, resulted in
      the premature fusion of eggshell protein globules within the vitelline cells and
      premature tanning of the eggshell protein material. The copper-containing enzyme,
      phenol oxidase, is thought to be involved in the tanning process during the
      production of eggs. Diethyldithiocarbamate, (DDC, 1 x 10(-3) M) is a phenol
      oxidase inhibitor and treatment with this compound, in combination treatments
      with monensin and NH4Cl, prevented fusion of the vitelline cell globules and
      tanning of the shell protein material. The results of the study suggest that the
      mechanism for eggshell formation in F. hepatica is similar to that proposed for
      S. mansoni and may be common to other trematodes as well.

PMID- 9651940
TI  - Changes in the zymogenic cell populations of the abomasa of sheep infected with
      Haemonchus contortus.
AB  - The effects of dietary urea supplementation and of a 10-week trickle infection
      regime, simulating chronic exposure to Haemonchus contortus, on the zymogenic
      population of the abomasa of Hampshire Down lambs was examined. At necropsy a
      variety of parameters including plasma pepsinogen concentration, the wet weights
      of abomasal fundic mucosal pieces and the amounts of pepsinogen contained in
      them, were assessed. Tissue pepsinogen concentration was measured as the total,
      acid-stable proteolytic activity present in mucosal homogenates, as well as
      immunohistochemically. The immunohistochemical findings were quantified using
      computer-aided image analysis. Elevation of plasma pepsinogen concentrations in
      infected animals was of borderline significance (P = 0.06). The fundic mucosae of
      infected animals were heavier (P < 0.02) than those of control animals, but there
      was no overall change in the pepsinogen content of tissues. Immunohistochemistry
      revealed that infected animals had increased numbers of zymogenic cells, due to
      mucous cell hyperplasia and the adaptation of cells to produce both mucins and
      pepsinogen. The pepsinogen content of chief cells, the major source of pepsinogen
      in uninfected animals, was reduced in infected lambs. Image analysis confirmed
      that at a mid-point of the mucosa of infected animals there was increased
      pepsinogen-specific immunoreactivity that corresponded with areas of mucosal
      hyperplasia. Mucous cell hyperplasia might therefore allow the maintenance of
      pepsinogen secretion in infected animals even if chief cell output is reduced.

PMID- 9651941
TI  - The relationship between numbers of larvae recovered from the brain of Toxocara
      canis-infected mice and social behaviour and anxiety in the host.
AB  - The effect of the nematode Toxocara canis on social behaviour and anxiety levels
      of adult male outbred (LACA) mice was examined following infection with a single
      dose of 2000 ova. The actual number of larvae recovered from the brain of each
      individual mouse was determined after behavioural testing. The effect of the
      parasite on mouse behaviour was analysed by both the initial dose administered
      (i.e. infected versus control) and the degree of infection in the brain. There
      was substantial variation in the number of larvae recovered from the brains of
      the individual mice and the magnitude of behavioural change was associated with
      the level of infection. Examination of social behaviour for both analyses
      revealed that the infection reduced levels of aggressive behaviour and increased
      levels of flight and defensive behaviours. High infection in the brain induced
      the greatest degree of behavioural change which decreased in mice with lower
      infections. In contrast the analysis of anxiety levels in mice by initial dose
      administered revealed no difference between infected and control mice. Mice with
      low infection in the brain, however, displayed a greater level of risk behaviour
      by spending more time in the vicinity of a predator odour and in the light area
      of a light/dark paradigm than control or high infection mice. The results suggest
      that the behaviour of mice infected with T. canis is influenced by the number of
      larvae accumulated in the brain. This may have important consequences for the
      conclusions drawn on the effect of this parasite on murine behaviour.

PMID- 9651942
TI  - In memory of Professor Olav Hilmar Iversen.

PMID- 9651943
TI  - Altered topographic expression of p21WAF1/CIP1/SDI1, bcl2 and p53 during gastric
      carcinogenesis.
AB  - The accumulation of wild-type p53 protein results in two pathways, cell cycle G1
      arrest by p21WAF1/CIP1/SDI1 and apoptosis inhibited by bcl2, which together carry
      out the tumor suppressor function. Since genetic alterations of p53 are
      frequently observed in gastric cancers, the expression of p21 and bcl2 may be
      altered in gastric carcinogenesis. We therefore analyzed normal mucosa,
      nondysplastic lesions, hyperplastic polyps, adenomas and carcinomas of the human
      stomach using immuno-histochemistry, polymerase chain reaction-single-strand
      conformation polymorphism and DNA sequencing. In normal gastric mucosa, the
      expression of p21, bcl2 and p53 was topographically restricted: a) p21 expression
      was limited to foveolar epithelial cells; b) bcl2 and p53 expression was confined
      to only a few regenerative epithelial cells of the mucous neck region. In chronic
      gastritis or intestinal metaplasia, topographic expression became more obvious.
      This topographic expression was altered in hyperplastic polyps and adenomas.
      Hyper-plastic polyp showed an increased p21 and p53 expression with no bcl2
      expression. Where as bcl2 expression increased and extended up parabasal and
      superficial dysplastic epithelium, p21 expression increased and was limited to
      surface dysplastic epithelium. Weak p53 expression was in full thickness of
      dysplastic epithelium. p21 and bcl2 expression in adenoma was higher than in
      intestinal type of carcinoma. In carcinomas, this topography was abrogated, but
      p53 mutation (36%) was present. There was no relationship between p53, p21 and
      bcl2 expression. As a result, in normal gastric epithelial cells, there was a
      precisely ordered topographic pattern of p21, bcl2 and wild-type p53 expression
      that becomes disordered during neoplasia. These results suggest that altered cell
      cycle and apoptosis control by wild-type p53 and its mediators appears to be an
      early event in gastric carcinogenesis that may facilitate tumor progression.

PMID- 9651944
TI  - Prognosis in lower lip squamous cell carcinoma: assessment of tumor factors.
AB  - We studied a consecutive series of 54 cases of lower lip squamous cell carcinoma
      (LLSCC) in order to identify any variables which might predict the development of
      lymph node metastases. The cases were divided into 38 tumors without metastases
      (group I) and 16 tumors with lymph node metastases (group II). The following
      factors were investigated: tumor size, histologic grading maximal thickness,
      perineural invasion, DNA ploidy and PCNA expression. In conclusion, we found that
      LLSCC greater than 2 cm in diameter, with histological grading G3-G4, thickness
      of more than 6 mm, DNA aneuploidy and high PCNA expression (PCNA LI > 0.48), were
      at high risk for the development of lymph node metastases.

PMID- 9651945
TI  - DNA ploidy pattern in papillary renal cell carcinoma. Correlation with
      clinicopathological parameters and survival.
AB  - Papillary renal cell carcinoma (PRCC) is a less frequent histomorphologic variant
      of renal cortical carcinoma (RCC). Morphologically, PRCC differs from other forms
      of RCC in that it is associated with frequent tumor infiltration by macrophages
      and lymphocytes, and a tendency for central necrosis and cystic change. Follow-up
      data revealed that survival rates are higher among patients with PRCC than among
      patients with other forms of RCC. The authors explore the DNA content in a series
      of PRCC and correlate the findings with nuclear grade, pathological stage and
      survival. Using Flow Cytometry, we analysed the DNA ploidy pattern of 37 paraffin
      embedded PRCC. At least 3 tumor fragments were analysed in each case. To obtain
      the reference diploid standard, the non-tumor renal tissue from the same case was
      added to the solution. Tumor ploidy was classified as diploid and aneuploid. The
      degree of DNA content abnormalities was given by the DNA Index (DI). An aneuploid
      DNA profile was found in 65% of the tumors. 25% of the aneuploid tumors presented
      near diploid peaks (1.10 < DI < 1.30; low degree aneuploidy), 25% were
      hyperdiploid, while 22% had a hypodiploid profile (DI < 0.90). A homogeneous DNA
      ploidy pattern was observed in 25 tumors (68%), while there was intratumoral
      heterogeneity in 12 tumors (32%). Patients with aneuploid DNA patterns had high
      grade/stage tumors and died at the end of the follow-up period, while patients
      with diploid/near diploid profiles had low grade/stage tumors and survived.
      However, the multi-way analysis of variance performed in order to investigate the
      prognostic significance of ploidy pattern against tumor stage and grade showed a
      highly significant main effect of ploidy pattern. Moreover, the patients with
      hypodiploid DNA profile presented the worst prognosis. These results suggest that
      the DNA profile of PRCC is a highly significant prognostic index.

PMID- 9651946
TI  - Expression of monocyte chemotactic protein-1 in human invasive ductal breast
      cancer.
AB  - Monocyte chemotactic protein-1 (MCP-1) is a chemokine involved in the macrophage
      infiltration of tumor tissue. Tumor associated macrophages (TAMs) are a
      population of mononuclear-phagocytic cells, which can express complex functions
      related to tumor biology. The present study was designed to analyse the
      expression of MCP-1 in parenchymal and stromal elements on frozen sections of 27
      breast invasive ductal carcinomas not otherwise specified (NOS) by
      immunohistochemistry. The expression of MCP-1 in tumor parenchyma and the degree
      of tumor differentiation were assessed. MCP-1 was detected in the parenchyma in
      15 of 27 ductal carcinomas. Positive immunoreactivity manifested as diffuse,
      homogeneous, moderate or strong, cytoplasmic staining, confined to tumor
      epithelium. Generally, MCP-1-negative tumors tended to be well differentiated,
      while chemokine-positive tumors exhibited a low level of differentiation. MCP-1
      immunoreactivity was also present in TAMs (CD68 positive cells) in 23 of 27
      tumors, and in endothelial cells in 11 of 27 tumors. These results indicate that
      parenchymal and, more variably, stromal elements of human invasive ductal
      carcinomas NOS can express MCP-1 in vivo. Additionally, these findings suggest
      that MCP-1 expression in tumor parenchyma is correlated with the histological
      grade of ductal invasive breast carcinoma.

PMID- 9651947
TI  - Warthin-like tumor of the thyroid: a papillary carcinoma with mitochondrion-rich
      cells and abundant lymphoid stroma. A case report.
AB  - Papillary carcinoma is the most common form of thyroid carcinoma and, generally,
      it has a more favorable prognosis than other carcinoma types, although diverse
      variants or subtypes have been described, some of which appear to have a less
      favorable prognosis. Recently, a new variant, the so-called "Warthin-like tumor"
      or "tall-cell variant with extensive lymphocytic infiltration of papillary
      thyroid carcinoma" with behavior similar to the usual papillary carcinoma, has
      been described. We present a case with the cytohistological pattern of "Warthin
      like tumor" of the thyroid. Immunohistochemistry revealed reactivity at the
      epithelium lining papillae for antimitochondrial 113-I antibody and also
      membranous positivity for CD15 (Leu M1). Lymphoid stroma showed an immunoprofile
      similar to chronic lymphocytic thyroiditis. These findings point to the
      consideration of "Warthin-like tumor" as being a hybrid neoplasm between the tall
      cell variant and oxyphilic papillary carcinoma associated to a lymphoid-rich
      stroma.

PMID- 9651948
TI  - Muscular hamartoma of the breast. Case report and review of the literature.
AB  - Muscular hamartoma (MH) is a rare tumor-like lesion of the breast, and only 22
      cases have been reported in the literature. We report an additional case of MH of
      the breast, giving a new immunocytochemistry-based insight into the histogenesis
      of the smooth muscle component. The expression of CD34 antigen in smooth muscle
      cells suggested that MH originates from stromal cells via leiomyomatous
      metaplastic changes. This hypothesis was supported by the evidence that stromal
      cells in the normal parenchyma nearby the hamartoma were positive for CD34
      antigen and, focally, also positive for smooth muscle markers (alpha-smooth
      muscle actin and desmin). A complete list of differential diagnoses and a review
      of the literature on the topic are provided. Although the use of the term
      "muscular hamartoma" could be considered inappropriate because of the absence of
      smooth muscle tissue in the normal breast, the authors underline that this
      designation can be easily accepted if the histogenesis of the heterologous
      component is regarded as a result of a stromal cell metaplastic change.

PMID- 9651949
TI  - Rhabdomyosarcoma with rhabdoid-like features.
AB  - We describe an unusual case of a rhabdomyosarcoma (RMS) in that it had rhabdoid
      like cells histologically and occurred in a female who had undergone bone marrow
      transplantation for chronic myelogenous leukemia. The tumor was composed of
      loosely cohesive cells with abundant eosinophilic cytoplasm and exhibited PAS
      negative paranuclear inclusions. The tumor cells had positive vimentin, muscle
      specific actin, sarcomeric actin and desmin immunoreactivity. Ultrastructurally,
      the tumor cells contained aggregates of thin and thick filaments. In situ
      hybridization did not detect human papillomavirus or cytomegalovirus DNA, or EBV
      DNA or RNA. The tumor fulfilled the current criteria for a diagnosis of RMS;
      however, it could not be further classified. The tumor appears to have a good
      prognosis as there has been no evidence of recurrence five years after resection.
      As this is the first case report, to our knowledge, of this type of tumor
      following bone marrow transplant, the significance of this association is not yet
      clear.

PMID- 9651950
TI  - Moyamoya disease with concurrent von Recklinghausen's disease and cerebral
      arteriovenous malformation.
AB  - We present a rare autopsy case of von Recklinghausen's disease with Moyamoya
      vessels and arteriovenous malformation. A 58-year-old female patient suffered
      from dysarthria and dysphagia. On examination, Parkinson's signs, pseudobulbar
      palsy, and muscular weakness of the left extremity and pyramidal tract signs were
      observed. An enhanced brain computed tomography revealed abnormal high-density
      network vessels at the thalamus and midbrain. By cerebral angiography, the
      following changes were observed; occlusion of the right internal carotid artery
      at the bifurcation, and abrupt narrowing and occlusion of the left internal
      carotid artery at the bifurcation and siphon. A lateral vertebral arteriography
      revealed telangiectasia at the basilar tip. The patient died of pulmonary
      thromboembolism at age 61. The vessels of the circle of Willis were hypoplastic.
      The optic nerves, infundibulum and mammillary body were covered with a large
      number of ectastic vessels. Arteriovenous malformations were observed in the
      bilateral occipital lobes. Histopathologically, the elastic lamina of Moyamoya
      vessel was conspicuously wavy and often duplicated or triplicated, and
      discontinued occasionally. Discontinuity of the elastic lamina of the perforating
      arteries and circumferential arteries supplied by the middle cerebral artery
      (MCA), anterior CA (ACA) and posterior CA (PCA), was also occasionally observed.
      It is likely that the Moyamoya vessels in this patient were compensatorily formed
      by congenital hypoplasia of the internal artery, MCA, ACA and PCA.

PMID- 9651951
TI  - Well differentiated cerebellar tissue within a mature cystic teratoma.
AB  - We describe the case of a 27 year-old woman presenting with acute abdominal pain
      due to torsion of a right ovarian cyst. Histopathological examination of the
      excised lesion revealed a mature cystic ovarian teratoma consisting primarily of
      a highly organized cerebellar component, an exceedingly rare finding. The
      possibility of a malignant neuroepithelial tumor arising from immature precursor
      cells within this neural tissue justifies complete excision of such lesions.

PMID- 9651952
TI  - A two-dimensional array for B-mode and volumetric imaging with multiplexed
      electrostrictive elements.
AB  - A 2:1 multiplexed 2-D array has been developed that has a sparse element pattern
      designed for real time volumetric imaging and an alternate element pattern
      designed for B-mode imaging. For volumetric imaging, a small aperture was used to
      provide a wide transmit beam, allowing multiple beams to be received
      simultaneously. For B-mode imaging, a larger aperture with a more narrow transmit
      beam was used to improve image quality. Sparse random element patterns were
      evaluated by beamplot and cyst image simulations. Using the alternate element
      pattern for B-mode imaging, simulated cyst contrast was improved by 28%. The
      multiplexed transducer was fabricated using an electrostrictive material in which
      array elements were activated and deactivated by a dc bias field. The transducer
      had a 3.4 MHz center frequency with 46% bandwidth, which was consistent with KLM
      simulations. The high dielectric constant of the electrostrictive material
      resulted in an element clamped capacitance of 14.3 pF versus 2 pF for a
      convention PZT element. An output off isolation of -35 dB was measured for
      transmit and -61 dB for receive. The array was integrated with the volumetric
      scanner and used to make real time images of a cyst phantom. The images showed
      improved cyst contrast using the alternate aperture for B-mode imaging.

PMID- 9651953
TI  - Spatial compounding in 3D imaging of limbs.
AB  - Effects of spatial compounding on image resolution and speckle noise are studied.
      Using computer simulation, it is shown that spatial compounding using averaged
      reconstruction can significantly improve lateral resolution while slightly
      deteriorate axial resolution. The amount of net resolution improvement depends
      mainly on the compound angle, but is insensitive to the number of component
      images used in compounding. While the fact that spatial compounding can
      effectively reduce speckle noise is well known, the analysis in this paper
      indicates that to maximize speckle reduction, the component echo amplitudes must
      meet two conditions: to be mutually independent and to have the same mean power.
      These findings provide useful guidelines for the analysis and optimization of the
      performance of an ultrasound scanning system that has been specially developed
      for imaging residual limbs.

PMID- 9651954
TI  - Spectral analysis of demodulated ultrasound returns: detection of scatterer
      periodicity and application to tissue classification.
AB  - Ultrasound returns from tissue display variations in amplitude on several spatial
      scales. Although large-scale variations result from factors such as attenuation,
      variations on smaller scales are caused by tissue characteristics such as
      variations in scatterer spacing and reflectance. These small scale variations
      cause a corresponding variation in the amplitude of the ultrasound return. A
      simple and direct method for detecting and quantifying periodicity in these
      variations in the presence of attenuation is described. The radiofrequency
      ultrasound return is first demodulated by full-wave rectification. The normalized
      power spectrum of the demodulated return then yields an index that we call the
      relative Fourier energy. Both computer simulations and in vitro experiments were
      performed in order to study how relative Fourier energy performed in
      discriminating between periodic and random scatterer distributions. Computer
      simulations demonstrated significant differences between the returns from
      periodic and random scatterer distributions. Ultrasound returns from aortic
      tissue yielded a relative Fourier energy index that was significantly different
      between normal vs. atherosclerotic tissue (normal: 0.868 +/- 0.076, mean +/-
      s.d., fibrofatty plaque: 0.705 +/- 0.109, p < 0.01 vs. normal, calcified plaque:
      0.753 +/- 0.078, p < 0.01 vs. normal). In contrast, no difference was found in
      comparisons of overall reflectance.

PMID- 9651955
TI  - High resolution low frequency ultrasonic tomography.
AB  - Ultrasonic reflection tomography results from a linearization of the inverse
      acoustic scattering problem, named the inverse Born approximation. The goal of
      ultrasonic reflection tomography is to obtain reflectivity images from
      backscattered measurements. This is a Fourier synthesis problem and the first
      step is to correctly cover the frequency space of the object. For this inverse
      problem, we use the classical algorithm of tomographic reconstruction by
      summation of filtered backprojections. In practice, only a limited number of
      views are available with our mechanical rig, typically 180, and the frequency
      bandwidth of the pulses is very limited, typically one octave. The resolving
      power of the system is them limited by the bandwidth of the pulse. Low and high
      frequencies can be restored by use of a deconvolution algorithm that enhances
      resolution. We used a deconvolution technique based on the Papoulis method. The
      advantage of this technique is conservation of the overall frequency information
      content of the signals. The enhancement procedure was tested by imaging a square
      aluminium rod with a cross-section less than the wavelength. In this application,
      the central frequency of the transducer was 250 kHz so that the central
      wavelength was 6 mm whereas the cross-section of the rod was 4 mm. Although the
      Born approximation was not theoretically valid in this case (high contrast), a
      good reconstruction was obtained.

PMID- 9651956
TI  - Multiple-transducer scheme for scanning tomographic acoustic microscopy using
      transverse waves.
AB  - We propose a new type of multiple-transducer scheme with functions of multiple
      angle and multiple-frequency tomography for scanning tomographic acoustic
      microscopy (STAM) using transverse waves. We review the data acquisition system
      and mode conversion of the acoustic waves for STAM and the multiple-angle and
      multiple-frequency tomography. Our multiple-transducer scheme has three
      insonification angles and three resonance frequencies in order to operate, in the
      transverse wave mode, multiple-angle and multiple frequency tomography for STAM.
      In order to evaluate the performance of our transducer scheme, we have simulated
      tomographic reconstruction with a back-and-forth propagation algorithm.
      Simulation results show that our multiple-transducer scheme is capable of
      obtaining good resolution with transverse wave mode and multiple-frequency
      tomography. We also show that our multiple-transducer scheme is an efficient
      rotation tool for a number of projections.

PMID- 9651957
TI  - Blood flow through the ductus venosus in human fetus: calculation using Doppler
      velocimetry and computational findings.
AB  - The present study was performed to assess a new method to calculate the blood
      flow rate through the ductus venosus (DV) in normal human fetuses using available
      echo-Doppler data. Color Doppler sonographic unit was used to study DV flow in 26
      normal fetuses between 20 and 36 wk of gestation. Maximal velocity flow tracings
      and vessel diameters were obtained at the isthmic and the outlet portion of the
      DV. Time-averaged velocities in the DV were measured from the recorded tracings.
      The velocity distribution in the two investigated cross-sectional areas of the DV
      was evaluated by means of computational model simulations and the velocity shape
      coefficients h(in) and h(out), (i.e., the ratios between the maximal and mean
      spatial velocities) were calculated as a function of vessel geometry. These
      values allowed us to convert maximal Doppler velocities into mean spatial
      velocities for each fetus. Blood flow rate was evaluated both at the isthmus and
      at the outlet of the vessel by means of two formulae based on the
      ultrasonographic measures and the results of the computational model. The value
      of the DV blood flow rate was calculated as the average between the results
      provided by the two formulae. The velocity distributions both at the isthmus
      (h(in) = 0.677 +/- 0.040) and the outlet (h(out) = 0.374 +/- 0.072) of the ductus
      are skewed toward the inner wall. Ductus geometry, i.e., the isthmic/outlet
      diameter ratio, affects the shape of the velocity profiles in the vessel,
      particularly that at the outlet. The coefficients of variation for repeated
      measurements of the ductal diameters were 9.5 +/- 7.7% and 6.7 +/- 4.9% at the
      isthmus and the outlet, respectively. The two formulae gave values statistically
      identical for the time-average blood flow rate (36.3 +/- 22.1 vs. 39.4 +/- 24.0
      mL/min; R = 0.946, p = NS). The mean percent difference between the results of
      the two formulae was 7.1%. Thus, in human fetuses, the use of the two formulae
      based on both Doppler data and computational model simulations makes it possible
      to calculate the ductal flow rate. When the difference between the calculations
      of the two formulae exceeds the 30% of their average value, it is convenient to
      adopt the flow rate value calculated at the isthmus instead of the average of the
      two measures. The measurements at the outlet of the ductus were more difficult to
      obtain, and the spatial velocity profile at the outlet depends more on the DV
      anatomy.

PMID- 9651958
TI  - Ultrasonographic characterization of carotid plaques.
AB  - The composition of atherosclerotic plaques in the carotid artery is assumed to be
      related to the development of neurological symptoms. The echo patterns produced
      by B-mode ultrasound may be of use in the assessment of the plaques' composition.
      It is suggested that fibrotic and "stable" plaques are more echogenic than
      lipid/hemorrhagic and echolucent or "unstable" plaques. B-mode ultrasound
      procedures were performed 1 day prior to surgery on 46 consecutive
      endarterectomies. Two observers assessed the plaques according to their echo
      pattern and echogenicity and sorted them into three categories: 1) predominantly
      echolucent, 2) heterogeneous, and 3) predominantly echogenic. The intraobserver
      agreement was moderate (kappa = 0.44) and the interobserver agreement low (kappa
      = 0.38). Furthermore, subjective categorization of plaque types resulted in type
      1 plaques being as fibrotic as type 2 or 3 plaques. We conclude that B-mode
      ultrasound and subsequent subjective categorization of atherosclerotic plaques
      cannot adequately determine the volume of fibrosis or lipids within the plaque.

PMID- 9651959
TI  - Contrast-enhanced sonography of tumor neovascularity in a rabbit model.
AB  - This project was designed to detect the development of tumor neovascularity and
      determine if intravenous microbubble contrast improves visualization of otherwise
      undetectable tumors in an animal model. VX-2 carcinoma was implanted into one
      thigh of 10 New Zealand white rabbits. Tumors were assessed without and with
      contrast at 1- to 4-day intervals from day 3-19 postimplantation, using gray
      scale, color flow, pulse Doppler and power Doppler imaging. Tumor vascularity was
      compared with the contralateral thigh muscle, so each animal was its own control.
      Contrast injection improved visualization of tumor neovascularity. Early tumors
      had homogeneous vasculature but, with time, the centers became less vascular,
      while the periphery increased. Following contrast injection, color gain was
      decreased by 40% without compromising color intensity. Neovascularity was
      detected by contrast injection before the tumor could be palpated or visualized
      by gray scale. Based on these data, we conclude that enhancement of
      neovascularity by intravenous contrast permits earlier detection and improved
      visualization of soft tissue tumors in rabbits.

PMID- 9651960
TI  - Effects of a sudden flow reduction on red blood cell rouleau formation and
      orientation using RF backscattered power.
AB  - In most studies that were aimed at evaluating the kinetics of red blood cell
      (RBC) aggregation, human blood was initially circulated at a high shear rate to
      disrupt the aggregates, and measurements were performed following a complete flow
      stoppage, during the process of rouleau formation. However, it is known that a
      very low shear rate can enhance the formation of aggregates, as demonstrated by
      the modal relationship of the shear-rate dependence of RBC aggregation. The
      objective of the present study was, thus, to evaluate the influence of sudden
      flow reductions compared to a complete flow stoppage on the kinetics of rouleau
      formation, using ultrasound backscattering. Horse blood models, characterized by
      different aggregation levels, were obtained by diluting the plasma with a saline
      solution in different proportions. Blood was circulated in a 12.7-mm vertical
      tube at a flow rate of 1250 mL min-1 (prereduction flow rate) to disrupt the
      aggregates. The ultrasound radiofrequency (RF) signal was recorded from the
      center of the tube following different levels of sudden flow reduction or
      complete stoppage (postreduction flow rate). All measurements were performed over
      2 min, using a 10-MHz transducer. No power increase was observed after complete
      flow stoppage. For postreduction flow rates varying between 20 and 160 mL min-1,
      the backscattered power increased proportionally with the kinetics of RBC
      aggregation. The echo buildup was also faster and stronger when the postreduction
      flow rate was increased. An unexpected pattern of variation of the backscattered
      power was found for horse RBCs characterized by high kinetics of rouleau
      formation. The power increased rapidly to a plateau, followed by another rapid
      increase and another plateau. Rouleau formation, random disorientation and
      reorientation were postulated to explain the phasic power increases observed.

PMID- 9651961
TI  - Onset delay of acoustic second harmonic backscatter from bubbles or microspheres.
AB  - A well-known method of enhancing blood detectability in ultrasound imaging of
      tissues detects the second harmonic of the incident radiation, which is generated
      by ultrasound contrast agents in the form of bubbles or microspheres that may
      have been injected into the blood. We report here a delay in the onset of the
      backscattered second harmonic with respect to the backscattered first harmonic
      for these agents. This effect, which should limit the axial resolution attainable
      with harmonic imaging, is investigated by simulation as well as experiment, and
      its dependence on the incident ultrasonic amplitude and microsphere parameters is
      established.

PMID- 9651962
TI  - Acoustic modeling of shell-encapsulated gas bubbles.
AB  - Existing theoretical models do not adequately describe the scatter and
      attenuation properties of the ultrasound contrast agents Quantison and Myomap. An
      adapted version of the Rayleigh-Plesset equation, in which the shell is described
      by a viscoelastic solid, is proposed and validated for these agents and Albunex.
      The acoustic transmission and scattering are measured in the frequency band from
      1-10 MHz. The measured transmission is used to estimate two parameters, the
      effective bulk modulus, Keff, describing the elasticity, and the friction
      parameter, SF, describing the viscosity of the shell. For the scattering, the
      difference between measurements and calculations is < 3 dB. For Quantison, the
      effective bulk modulus is independent of the bubble diameter. For Albunex, it
      increases for decreasing bubble diameter. The nonlinear response of Quantison is
      minimal for acoustic pressures up to 200 kPa. For acoustic pressures above 200
      kPa, the measured scattering abruptly increases. This increase reaches a level of
      20 dB for an acoustic pressure of 1.8 MPa. This response cannot be predicted by
      the theoretical model developed in this article.

PMID- 9651963
TI  - Liquid or solid ultrasonically tissue-mimicking materials with very low scatter.
AB  - A new tissue-mimicking material for ultrasound, using evaporated milk as the
      primary absorption component, is described. It has very low backscatter but still
      exhibits the 1540 m s-1 propagation speed and proportionality of attenuation
      coefficient and frequency over the diagnostic frequency range. The material can
      be produced in solid or liquid form with attenuation coefficient slopes spanning
      the range 0.1-0.7 dB cm-1 MHz-1. The liquid form is useful in phantoms where
      detailed beam patterns are to be determined, either involving translation of
      measurement devices in the liquid or phantoms with fibers present for causing the
      only detectable echoes. In the latter case, the liquid quality allows removal of
      liquid with one attenuation coefficient slope and replacement with another. The
      solid form may be more useful than the liquid for two reasons. First, many
      simulated lesions (including ones that produce essentially no internal echoes)
      can lie in the scan slice with positions extending over the entire image area
      without enhancement or shadowing effects being of concern. Second, the lack of
      significant backscatter from the material in the absence of added scatterers
      allows the backscatter coefficient to be varied over a considerable range. A
      critical result is that intrinsic material contrast between targets and
      surroundings can be accurately predicted in terms of the concentrations of added
      scatterers and, assuming all scatterers are of the same type, the contrast will
      be completely independent of frequency. Use of the fungicide thimerosal
      eliminates deterioration, and ultrasonic properties have been shown to be stable
      over 2.5 years.

PMID- 9651964
TI  - Characterization of elastographic noise using the envelope of echo signals.
AB  - A theoretical formulation characterizing the noise performance of strain
      estimation using envelope signals is presented for the cross-correlation based
      strain estimator in elastography, using a modified strain filter approach. The
      strain filter describes the relationship among the elastographic signal-to-noise
      ratio (SNRe), sensitivity, contrast-to-noise ratio and dynamic range for a given
      resolution in the elastogram, as determined by the cross-correlation window
      length and window overlap. Theoretical results indicate that the envelope strain
      filter noise performance (SNRe level) is about half that obtained in the ratio
      frequency (RF) case (fo = 7.5 MHz). Simulation results corroborate the trend
      predicted using the strain filter. Experimental SNRe vs. strain plots presented
      in this article illustrate the same trend as the theoretical results. These plots
      allow a quantitative comparison of the elastograms obtained with RF and envelope
      signal processing. For small strains, the performance obtained using RF signals
      is superior to that obtained for envelope signals (since jitter errors are
      smaller due to the utilization of phase information in RF signals). However, for
      large tissue strains, envelope analysis provides an accurate estimate of the
      tissue strain (since envelope signal decorrelation is smaller than RF signal
      decorrelation at large strains). An algorithm that combines the low-noise
      characteristics of the cross-correlation analysis using RF signals at small
      strains and envelope signals for estimation of large tissue strains is proposed
      to improve the dynamic range in the elastogram.

PMID- 9651965
TI  - Focused ultrasound modifications of neural circuit activity in a mammalian brain.
AB  - The application of focused, pulsed ultrasound was studied as a method of
      modifying the activity of a local neural circuit of the mammalian brain. An in
      vitro hippocampal preparation was used to facilitate delivery, dosimetry and
      assessment of mechanisms of ultrasound effects. Extracellular evoked potentials
      were recorded from cell and dendritic layers of the rat hippocampal dentate
      gyrus. Focused pulses of ultrasound with center frequency of 500 kHz and
      repetition rate of 200 kHz were studied and found both to enhance and to depress
      electrically evoked field potentials. The fiber volley and cell population
      potentials were depressed, whereas the dendritic potential was enhanced. Results
      suggest a simultaneous mechanical and thermal mechanism of ultrasound in
      modifying evoked field potentials of dentate local circuits.

PMID- 9651966
TI  - Application of low-intensity ultrasound to growing bone in rats.
AB  - Low-intensity pulsed ultrasound recently has been shown to accelerate long bone
      fracture healing, but its effect on bone growth and development is unknown. The
      longitudinal growth and bone density of the femur and tibia in young rats was
      measured after application of an ultrasound transducer emitting 1.5-MHz pulsed
      ultrasound (30 mW/cm2, SATA) for 20 min/day. After 28 days, no length difference
      was detected (< or = 2%) compared to the sham-treated leg or to unexposed
      controls. Also, no significant difference in bone mineral density (BMD) of the
      femur or tibia was found (< or = 6%). In a repeated experiment in which a
      periosteal trauma stimulus was created in the femoral diaphysis, the ultrasound
      also had no effect on growth or BMD. This results suggests that physeal bone
      growth is far less sensitive to this level of ultrasound application than is
      fracture repair. This may be related to the cascade of cellular events and
      regulatory factors that are present after a fracture.

PMID- 9651967
TI  - Effects of pulsed ultrasound on embryonic development: an in vitro study.
AB  - Whole-embryo culture was used as the model system to study the effects of pulsed
      ultrasound on embryonic development. Rat embryos (9.5 days old) were exposed to a
      wide range of ultrasound levels at ultrasound frequencies between 1-4 MHz for 30
      min in vitro. After 48 h in culture, absolute control, sham and treatment embryos
      were assessed for viability, morphology, growth and development. At an ambient
      temperature of 37 degrees C, no significant effects were observed for spatial
      peak temporal average intensities below 4 W/cm2 or peak negative pressures below
      1.9 MPa. At higher acoustic levels, there was a significant increase in the
      number of nonviable embryos and the number of morphological abnormalities in
      viable embryos increased. Abnormal cephalocaudal flexion and abnormal head
      development were the most common gross morphological abnormalities. Both thermal
      and nonthermal bioeffect mechanisms are involved.

PMID- 9651968
TI  - Artificial cavitation nuclei significantly enhance acoustically induced cell
      transfection.
AB  - The efficiency of ultrasound-mediated gene transfection was enhanced three- to
      fourfold, compared to previous results, through the use of green fluorescent
      protein reporter gene, cultured immortalized human chondrocytes and artificial
      cavitation nuclei in the form of Albunex. Cells were exposed to 1.0-MHz
      ultrasound transmitted through the bottom of six-well culture plates containing
      immortalized chondrocytes, media, DNA at a concentration of 40 micrograms/mL and
      Albunex at 50 x 10(6) bubbles/mL. Transfection efficiency increased linearly with
      ultrasound exposure pressure with a transfection threshold observed at a spatial
      average peak positive pressure (SAPP) of 0.12 MPa and reaching about 50% of the
      living cells when exposed to 0.41 MPa SAPP for 20 s. Adding fresh Albunex at 50 x
      10(6) bubbles/mL prior to sequential 1-s, 0.32- or 0.41-MPa exposures increased
      transfection with each exposure, reaching 43% transfection after four exposures.
      Efficient in vitro and in vivo transfection now appear possible with these
      enhancements.

PMID- 9651969
TI  - Gosling's Doppler pulsatility index revisited.
AB  - In Doppler sonography, the physiological meaning of Gosling's pulsatility index
      (PI) as a measure of downstream resistance is still under dispute. We deliver the
      theoretical derivation of its physiological significance. We present a
      mathematical model based on the linked theories of critical closing pressure
      (CCP) and cerebrovascular impedance, verified in preterm neonates. Mathematical
      transformation results in a series of equations interrelating several
      physiological parameters. Instead of indicating cerebrovascular resistance, PI is
      linked to the ratio of cerebrovascular impedances at the heart rate and at zero
      frequency. Next to arterial blood pressure, CCP is the principal determinant of
      PI. PI is identical to the ratio of the alternate and the direct component of the
      effective driving force. Thus, PI has no distinctive physiological meaning by
      itself. At present, our model is confined to physiological conditions where the
      lowest velocity is the end diastolic, and always more than zero.

PMID- 9651970
TI  - Influence of ECG-triggered data acquisition on reliability for carotid plaque
      volume measurements with a magnetic sensor three-dimensional ultrasound system.
AB  - Three-dimensional (3D) ultrasound reconstructions of the carotid arteries are
      based on multiple sections of two-dimensional data. Some 3D systems use an
      electrocardiography (ECG)-triggered data acquisition for 3D reconstructions of
      pulsatile vessels such as carotid arteries. No systematic comparison of 3D data,
      acquired with and without ECG triggering, has been reported. We used a new
      magnetic sensor system allowing freehand scanning for data acquisition. Our aim
      was to test the effect of ECG triggering on the reliability of plaque volume
      measurements in the carotid arteries. Data acquisition in the carotid arteries in
      25 patients (one plaque from each patient) was performed using two different
      procedures for data acquisition: 1) a magnetic sensor system for a data
      acquisition without ECG-triggering, and 2) a magnetic sensor system with ECG
      triggered data acquisition. All plaque volumes were measured using manual tracing
      of the outlines of the plaques. The following reliability data (mean values) were
      obtained: magnetic sensor system without ECG triggering: intrareader variability
      13.3%, interreader variability 16.7%, follow-up variability 16.3%; magnetic
      sensor system with ECG triggering: intrareader variability 4.6%, interreader
      variability 4.5%, follow-up variability 5.2%. Carotid plaque volume measurements
      obtained using a magnetic sensor system with freehand scanning and ECG triggering
      is highly reliable. ECG triggering is necessary, because a magnetic sensor system
      without ECG triggering resulted in reduced reliability for plaque volume
      measurements.

PMID- 9651971
TI  - Color flow mapping.

PMID- 9651972
TI  - Laryngeal paralysis: an introduction.

PMID- 9651973
TI  - Laryngeal paralysis: an emergency management.

PMID- 9651974
TI  - Laryngeal paralysis: surgical solutions.

PMID- 9651975
TI  - The chronic ear: diagnosis and medical management.

PMID- 9651976
TI  - Tumors of the external ear.

PMID- 9651977
TI  - The ear: surgery for chronic otitis.

PMID- 9651978
TI  - Pleural effusion: recent advances in diagnosis and treatment.

PMID- 9651979
TI  - Surgical diseases of the lung and chest wall: new development in the treatment of
      pneumothorax.

PMID- 9651980
TI  - Surgical oncology.

PMID- 9651981
TI  - Biopsy principles.

PMID- 9651982
TI  - Abdominal tumors.

PMID- 9651984
TI  - Skin tumors and mast cell cancer.

PMID- 9651983
TI  - Soft tissue sarcomas.

PMID- 9651985
TI  - Osteosarcoma.

PMID- 9651986
TI  - Canine hip dysplasia: pathogenesis, diagnosis, and genetic control.

PMID- 9651987
TI  - Triple pelvic osteotomy (TPO) for the treatment of hip dysplasia.

PMID- 9651988
TI  - Fractures and luxations of the elbow.

PMID- 9651989
TI  - Surgical treatment of elbow dysplasia.

PMID- 9651990
TI  - Professional periodontal therapy and home care.

PMID- 9651991
TI  - Endodontic treatment.

PMID- 9651992
TI  - Adhesive dentistry with direct restorative materials.

PMID- 9651993
TI  - Understanding feline diabetes: pathogenesis and management.

PMID- 9651994
TI  - Anemia in the dog and cat.

PMID- 9651996
TI  - Immune-mediated hemolytic anemia.

PMID- 9651995
TI  - Abnormal osmotic fragility of erythrocytes in dogs and cats.

PMID- 9651997
TI  - Disorders of hemostasis.

PMID- 9651998
TI  - Congenital (hereditary) clotting disorders in the dog.

PMID- 9651999
TI  - Immune-mediated thrombocytopenia.

PMID- 9652000
TI  - Diagnosis of liver disease in companion animals.

PMID- 9652001
TI  - Reactive hepatopathies and chronic hepatitis in the dog.

PMID- 9652002
TI  - Treatment of chronic hepatitis and management of biliary tract disorders.

PMID- 9652003
TI  - Injection anesthesia in companion animals.

PMID- 9652004
TI  - Inhalational anesthesia.

PMID- 9652005
TI  - Resuscitation.

PMID- 9652006
TI  - Anesthesia of patients with liver or renal disease.

PMID- 9652007
TI  - Cardiac disease and companion animal anesthesia.

PMID- 9652008
TI  - Emergency management ... and what's next?

PMID- 9652009
TI  - Fluid therapy in companion animal medicine.

PMID- 9652010
TI  - Catheters, drains, and tubes.

PMID- 9652011
TI  - Introduction to avian practice.

PMID- 9652012
TI  - Nursing avian patients.

PMID- 9652013
TI  - Avian nutrition.

PMID- 9652014
TI  - Avian anesthesia.

PMID- 9652015
TI  - Avian radiology and endoscopy.

PMID- 9652016
TI  - Avian respiratory disease.

PMID- 9652017
TI  - Avian orthopedics.

PMID- 9652018
TI  - Avian soft tissue surgery.

PMID- 9652019
TI  - Guidelines for obesity management in companion animals.

PMID- 9652020
TI  - Nutrition and gastrointestinal disease.

PMID- 9652021
TI  - Nutrition, metabolism, and cancer.

PMID- 9652022
TI  - Diet and kidney or liver failure.

PMID- 9652023
TI  - Metabolic needs of the injured: enteral feeding support of dogs and cats.

PMID- 9652024
TI  - Nutritional uniqueness of cats.

PMID- 9652025
TI  - A new method of tube esophagostomy in cats.

PMID- 9652026
TI  - Ultrasonography: principles, indications, and limitations.

PMID- 9652027
TI  - Ultrasonography of the cranial abdomen: liver, spleen, pancreas, and
      gastrointestinal tract.

PMID- 9652029
TI  - Radiographic diagnosis of tumors: bone, lung and abdominal tumors.

PMID- 9652028
TI  - Ultrasonography of the caudal abdomen: urogenital tract, and adrenals.

PMID- 9652030
TI  - The role of molecular genetics in the diagnosis of diseases in companion animals:
      an introduction.

PMID- 9652031
TI  - DNA analysis in paternity testing of dogs and cats.

PMID- 9652032
TI  - DNA analysis in diagnosis of von Willebrand disease in dogs.

PMID- 9652033
TI  - Molecular diagnosis of copper toxicosis in Bedlington terriers.

PMID- 9652034
TI  - Toxocara infections in dogs and cats and public health implications.

PMID- 9652035
TI  - Transsphenoidal hypophysectomy for the treatment of pituitary-dependent
      hyperadrenocorticism in dogs.

PMID- 9652036
TI  - Modulation of the GABAergic tone by benzodiazepine receptor ligands in chronic
      hepatic encephalopathy in the dog.

PMID- 9652037
TI  - Studies on the function of the urethra and bladder in continent and incontinent
      female dogs.

PMID- 9652038
TI  - Pharmacokinetics of marbofloxacin in renal impairment in the dog.

PMID- 9652039
TI  - Cardiomyopathy in the Irish wolfhound. A clinical study of 393 dogs by electro-
      and echocardiography and radiology.

PMID- 9652040
TI  - EEG-burst-suppression-controlled propofol anesthesia in the dog.

PMID- 9652041
TI  - Indicators of the genetic variation in five dog breed populations in The
      Netherlands.

PMID- 9652042
TI  - Immunophenotyping of skin-infiltrating T-cell subsets in dogs with atopic
      dermatitis.

PMID- 9652043
TI  - Fourteen week clinical evaluation of an oral antioxidant as a treatment for
      osteoarthritis secondary to canine hip dysplasia.

PMID- 9652044
TI  - An alternative premedication and induction regime for cats with a decreased
      cardio-vascular reserve.

PMID- 9652045
TI  - Plasma ACE inhibition by five different ACE inhibitors.

PMID- 9652046
TI  - Progressive destruction of the elbow joints in a dog with leishmaniasis.

PMID- 9652047
TI  - Hyperadrenocorticism caused by an adrenal carcinoma in a parrot.

PMID- 9652048
TI  - Canine intestinal leiomyosarcoma.

PMID- 9652049
TI  - Polycystic kidney disease in cats.

PMID- 9652050
TI  - Successful treatment of neosporosis in an adult dog.

PMID- 9652051
TI  - A retrospective evaluation of 51 dogs with insulinoma.

PMID- 9652052
TI  - Differentiating infection from vaccination in foot-and-mouth disease.

PMID- 9652053
TI  - Serodiagnostic strategy for estimation of foot-and-mouth disease viral activity
      through highly sensitive immunoassays using bioengineered nonstructural proteins.

PMID- 9652054
TI  - Antibody to the nonstructural proteins of foot-and-mouth disease virus in
      vaccinated animals exposed to infection.
AB  - Cattle which have been infected with foot-and-mouth disease (FMD) virus can be
      differentiated from those that have been vaccinated on the basis of the detection
      of antibody to one or more of the non-structural (NS) proteins of the virus.
      Cattle which have been protected by vaccination can become persistently infected
      with FMD virus (FMDV) without ever showing clinical signs. Vaccinated, protected
      cattle which are persistently infected cannot be distinguished from animals that
      merely have been vaccinated on the basis of serological tests for antibody to the
      structural proteins of FMDV. Sera were collected from groups of cattle for
      varying periods after exposure to infection under experimental conditions. On the
      basis of isolation of virus from probang samples collected during the course of
      the experiments it was possible to classify the cattle according to the following
      criteria; naive, infected and eliminated the virus (convalescent), infected and
      persistently infected with FMDV (carriers), vaccinated alone, vaccinated and
      either convalescent or carrier. Sera were examined for antibody to the NS
      proteins Lb, 2C, 3A, 3D, and 3ABC by an indirect profiling ELISA using E. coli
      expressed fusion proteins as antigens. Considerable variation was observed in the
      antibody response to NS proteins of both naive and vaccinated animals following
      infection. The extent of individual variation was so great that convalescent
      animals could not be differentiated from carrier animals on the basis of their
      antibody response to any of the NS proteins examined. The majority of vaccinated,
      protected animals showed an antibody response to NS proteins, particularly 3ABC,
      following exposure to infection. However, the carrier state was demonstrated in
      some vaccinated, protected animals in which no antibody response to any of the NS
      proteins could be detected. The detection of antibody to NS proteins can
      therefore be used on a group, or herd, basis to detect circulation of virus in a
      vaccinated population but further investigations in the field are required to
      determine the sampling level necessary for statistical acceptance. On an
      individual animal basis, however, freedom from antibody to NS proteins in a
      vaccinated animal, or an animal of unknown history, does not necessarily imply
      that the animal is free from infection with FMD virus and, furthermore, the titre
      of antibody to NS proteins is not a useful predictive measure of whether or not
      an infected animal has successfully eliminated the virus.

PMID- 9652055
TI  - Differentiating foot-and-mouth disease virus-infected from vaccinated animals
      with baculovirus-expressed specific proteins.
AB  - We had shown in preliminary studies with a small number of animals that
      antibodies against 2C could be detected in cattle and pigs which had been
      infected with FMDV but not in animals which had been vaccinated against the
      disease. To determine whether this test was generally applicable, sera from
      several hundred animals which had been vaccinated with different products in many
      countries have been tested in an ELISA using baculovirus expressed 2C. Our
      results show that only 1-2% of the sera gave a positive reaction by this method.
      In contrast, 100% of sera from convalescent animals gave a positive reaction. To
      be useful in differentiating between convalescent and vaccinated animals it is
      necessary to know how long these antibodies can be detected by our ELISA. We have
      determined the levels of antibodies against 2C and also other virus-specific
      proteins which are present in cattle and pigs following infection with FMDV. Our
      results show that levels of anti-3ABC antibodies could be detected by ELISA with
      baculovirus-expressed protein up to one year after infection. In contrast, the
      levels of anti-2C antibodies fell more rapidly than those against 3ABC indicating
      that the latter protein may be preferable for detecting convalescent animals.
      Nevertheless, we envisage that the final test format should include several virus
      specific proteins to determine accurately the immune status of an animal.

PMID- 9652057
TI  - Blocking ELISAs using the FMDV non-structural proteins 3D, 3AB, and 3ABC produced
      in the baculovirus expression system.

PMID- 9652056
TI  - Cattle response to foot-and-mouth disease virus nonstructural proteins as
      antigens within vaccines produced using different concentrations.
AB  - Four groups of ten nine-month-old Nelore heifers were used for this study. Each
      group received one of four foot-and-mouth disease (FMD) trivalent vaccines for
      the duration of the experiment. The four vaccine formulations (Normal, 2X, 4X and
      8X) differed in 140S content to determine the serological reactivities to FMD
      virus (FMDV) nonstructural proteins 2C, 3ABC and 3D. Vaccination was by the
      intramuscular administration of vaccine on day 0, 180 and 360. Bleedings were
      done at 30 days post vaccination (dpv), 90 dpv, 30 days post revaccination (dpr),
      90 dpr, and 30 days post third administration (dprr). There was a general
      tendency to have higher mean 3D responses with increased vaccine application but
      not with increased concentration of antigen. With 2C and 3ABC this tendency was
      not seen, neither with repeated application of vaccine nor with increased antigen
      concentration. All individual animal observations to 2C and 3ABC remained within
      three standard deviations of the average observed for naive bovids. Percent of
      positive (PP) reactions was determined using an ELISA for nonstructural proteins
      2C, 3ABC and 3D expressed in baculovirus as previously described. A value of > 25
      PP to 2C or 3ABC could be considered as an indication of previous infection or of
      the presence of viral activity. PP results between 18 and 25 PP suggest viral
      activity and animals should be retested. Those responses below 15 PP are
      suggestive of vaccination or naive status. As diagnosis in the laboratory is not
      divorced from the field epidemiological scene, the intermediate zone between 10
      and 20 PP should be considered and acted upon according to the overall
      zoosanitary situation of that country or region and the purposes of the ongoing
      FMD control efforts.

PMID- 9652058
TI  - Diagnostic potential of Mab-based ELISAs for antibodies to non-structural
      proteins of foot-and-mouth disease virus to differentiate infection from
      vaccination.
AB  - This paper summarises the development of monoclonal antibody (Mab)-based
      immunoassays measuring antibodies to non-structural proteins of FMDV to
      differentiate infection from vaccination. Of the three non-structural proteins
      2C, 3C and 3ABC evaluated in this study, the polypeptide 3ABC was the most
      immunogenic. Three ELISAs for the detection of antibodies to 3ABC were developed.
      Two assays rely on the competition of test sera against either a anti-3A Mab or
      against antisera to 3ABC raised in rabbits and guinea-pigs. The third, 3ABC Mat
      ELISA, based on the direct binding of antibodies to the 3ABC trapped by a
      specific Mab, provided the best combination of specificity and sensitivity. The
      3ABC Mat-ELISA was extensively validated for cattle, either in experimental and
      in field conditions, showing specificity of 99% in vaccinated and in naive cattle
      and the capacity to detect silent infections in FMD-vaccinated populations. The
      test showed similar specificity and sensitivity in experimentally vaccinated and
      infected sheep.

PMID- 9652059
TI  - Detection of cattle exposed to foot-and-mouth disease virus by means of an
      indirect ELISA test using bioengineered nonstructural polyprotein 3ABC.

PMID- 9652060
TI  - The possible use of native foot-and-mouth disease non-structural protein 3A in a
      serological screening test.
AB  - ELISA's for antibodies to non-structural proteins of foot-and-mouth disease
      developed to date use recombinant proteins as antigens. To compare the antibody
      response to recombinant antigen and native antigen we developed an antigen
      capture ELISA for foot-and-mouth protein 3A. The concentration of 3A protein in
      virus cultures was significantly higher in the cell debris than in the
      supernatant, which made it possible to use proteins directly eluted from cells
      separated from virus culture using Filteraid. The antigen was trapped between one
      monoclonal antibody coated to the plate, and a second monoclonal antibody
      conjugated with horseradish peroxidase. The reaction of the second (conjugated)
      monoclonal antibody could be blocked by several post-infection sera. Further
      research has to be performed to determine whether or not this method can result
      in a reproducible serological test.

PMID- 9652061
TI  - Serological and cellular immune responses to non-structural proteins in animals
      infected with FMDV.
AB  - In order to provide a rational base for the evaluation of FMDV non structural
      proteins as diagnostic probes, we have performed systematic longitudinal studies
      of the humoral and cellular immune responses to these proteins in animals
      infected with different FMDV serotypes. Although primary antibody responses to
      all the non structural proteins were observed, antibody titres were highly
      variable, ranging from insignificant in some cases, to clearly positive in
      others. In general, even the obvious positive responses were of short duration.
      For this reasons, discrimination between infected and vaccinated cattle is only
      possible at a herd level, and in our experiments the most useful target was the
      non structural protein 3A, although addition of 2C and 3C would provide a more
      sensitive test. As an alternative, with the major advantage of use directly on
      living cattle in the field, recombinant non structural proteins were evaluated in
      Delayed Type Hypersensitivity (DTH) skin tests. With this test, which measures
      Th1 type cellular immune responses, the most T cell immunogenic non structural
      proteins were 2B, 2C and 3D. Thus, DTH skin test could be a very useful tool to
      differentiate infected from vaccinated cattle.

PMID- 9652062
TI  - Aims of the FMDV-specific RT-PCR as it is performed at the BFAV, Tuebingen
      laboratory.

PMID- 9652063
TI  - Application of RT-PCR and nucleotide sequencing in foot-and-mouth disease
      diagnosis.

PMID- 9652064
TI  - RT-PCR in foot-and-mouth disease diagnosis.
AB  - A RT-PCR assay for the specific detection of RNA sequences from foot-and-mouth
      disease virus (FMDV) has been developed. The procedure permits also the detection
      of sequences that correlate with established FMDV serotypes. A computer program
      that allows selection of genotype-specific primers for RT-PCR amplification was
      used for the identification of FMDV specific sequences for PCR amplification on
      RNA replicase (3D) gene regions. Specific, rapid and highly sensitive detection
      was achieved for a wide collection of RNA samples from FMDV types C, A and O,
      either purified from tissue culture or extracted from lesions of infected
      animals. Similarly, serotype-specific primers were designed to amplify the
      carboxy-terminal end of the VP1 gene of FMDV types either C, A or O. The results
      of PCR amplification of different FMDV RNAs using type-specific primers are in
      agreement with the serological typing of the corresponding viruses. A combination
      of this approach with a simplified sample processing, carried out following
      direct adsorption of viral suspensions to microtiter plates, provides a rapid,
      reliable method of viral diagnosis.

PMID- 9652065
TI  - Detection of foot-and-mouth disease by reverse transcription polymerase chain
      reaction and virus isolation in contact sheep without clinical signs of foot-and
      mouth disease.
AB  - Two non-vaccinated sheep were experimentally infected with FMDV and one day later
      4 other sheep were brought in contact. Although the contact sheep showed no
      clinical signs, serology indicated that all sheep became infected. Various
      secretion samples, taken over a period of at least one month, and various tissue
      samples were examined for the presence of FMDV by RT-PCR and by virus isolation.
      FMDV was most often found in saliva (mouth swabs), followed by nasal secretion
      and sera. Faecal material, wool and milk were less suitable. The period of
      detection with the highest frequency of positive isolations was between 2 to 4
      days pi for the infected sheep and between 5 to 10 days pc for the contact
      animals. It was established that in subclinically infected sheep, with a very low
      amount of virus present, FMD viral RNA could be detected by a sensitive RT-PCR
      ELISA although virus isolation and standard RT-PCR remained negative. Moreover
      there was some evidence of active spreading of FMDV from the contact sheep to two
      sentinel pigs. This indicates that serologically positive contact sheep without
      clinical signs may be considered as a danger for the transmission of FMDV.

PMID- 9652066
TI  - Immunohistochemical localisation of a galectin from Bufo arenarum ovary.
AB  - Galectins are a group of soluble animal lectins that exhibit specificity for beta
      galactosides and conserve sequence homology in the carbohydrate-recognition
      domain. The galectin from Bufo arenarum ovary showed a strong cross-reaction with
      the lectin of 14.5 kDa purified from embryos at early blastula stage. In this
      paper, we studied the immunohistochemical localisation of the galectin of 14.5
      kDa from ovary of the toad B. arenarum in adult ovary sections. We also analysed
      the immunohistochemical localisation of the embryonic lectin during early
      development using the antiserum anti-ovary galectin. In the ovary, oocytes in the
      previtellogenic stage showed strong reactivity in the nucleus and the cortex but
      not in the cytoplasm. Oocytes in the stage of primary vitellogenesis exhibited a
      similar pattern in the nuclear and cortical areas but showed immunostaining in
      the cytoplasm. Intense nuclear staining was detected in oocytes in the stage of
      late vitellogenesis and in mature oocytes, which also presented strong reactions
      in the yolk platelets that completely covered the cytoplasm. In blastula embryos
      the staining was found in the blastomeres, the yolk platelets and the
      blastocoele. Each lectin localisation is discussed in relation to potential
      biological roles in the corresponding tissues.

PMID- 9652067
TI  - Non-specific currents at fertilisation in sea urchin oocytes.
AB  - Using the whole-cell voltage-clamp technique to clamp sea urchin oocytes we show
      that the fertilising spermatozoon triggers an inward current of -521 +/- 56.7 pA
      (n = 8) at activation. Simultaneously, the plasma membrane depolarises and the
      conductance increases from 23.4 +/- 1.4 to 40.6 +/- 1.2 nS (n = 8). The I/V curve
      for the peak activation current is linear and the current reverses between 0 and
      +20 mV, suggesting a non-specific ion current. Since injection of inositol
      triphosphate induced an inward current of -1062 +/- 314 pA (n = 4), and the
      current was inhibited by preloading oocytes with the calcium chelator BAPTA, the
      non-specific activation current in sea urchin appears to be calcium dependent.

PMID- 9652068
TI  - Ultrastructure of bovine in vitro-produced blastocysts cryopreserved by
      vitrification.
AB  - The objective of this study was to examine ultrastructural aspects of bovine in
      vitro-produced blastocysts associated with cryopreservation by vitrification.
      Morphologically good embryos were used and treated with ethylene-glycol-based
      vitrification solution (VS). The untreated embryos had conventional fine
      structure. The post-warming embryos treated with direct exposure to VS (one-step
      procedure) showed cellular damage structurally by cryopreservation, which
      included loss of microvilli, disruption of the plasma membrane, mitochondrial
      changes and swelling of the endoplasmic reticulum. However, nuclei and junctional
      regions seemed to be resistant to cryoinjury. In contrast, the post-warming
      embryos pre-equilibrated with 10% ethylene glycol for 5 min and subsequent
      exposure to VS (two-step procedure) showed less damage than those treated by the
      one-step procedure. Post-warming embryos treated by the two-step procedure were
      cultured in vitro for 18 h. Some embryos survived and their structures re-formed
      to the former state, while other embryos showed serious injuries and could not
      reconstitute the blastocoele. Three post-warming embryos treated by the two-step
      procedure that survived after in vitro culture were transferred to three
      recipients and one of these resulted in pregnancy. These results indicate that
      cryopreservation by vitrification can damage membranous structures of the cells
      of bovine embryos, the extent and nature of this damage being dependent on the
      vitrification procedure.

PMID- 9652069
TI  - Combined immunocytogenetic and molecular cytogenetic analysis of meiosis I
      oocytes from normal human females.
AB  - The microspread oocytes of three fetuses, two of 16 weeks gestation and one of 15
      weeks gestation, were labelled with a combination of anti-lateral element
      antiserum and a human centromere labelling auto-immune serum. The anti-lateral
      element serum was found to label both asynapsed axial elements and synapsed
      lateral elements strongly. Nuclei were found from leptotene to diplotene in all
      three fetuses. The use of the human auto-immune serum led to the observation of
      'staggered centromeres' and 'centromeric associations' as well as tightly
      clustered centromeres in 'stellar nuclei'. Nuclei displaying various aberrant
      features were detected. The use of antibody-labelled microspread oocytes as
      substrates for fluorescence in situ hybridisation (FISH) was found to be reliably
      successful only with repetitive (centromeric and telomeric) probes.

PMID- 9652070
TI  - Decondensation of the mouse sperm nucleus within the interphase nucleus.
AB  - Sperm nuclei incorporated into the cytoplasm (ooplasm) of fertilised mouse eggs
      at the pronuclear stage remain condensed, whereas those injected into male or
      female pronuclei decondense. Similarly, sperm nuclei injected into germinal
      vesicles of immature oocytes or the nuclei of 2-cell embryos decondense, while
      those entering the cytoplasm of these oocytes/embryos do not. These facts seem to
      suggest that factors necessary for the decondensation of sperm nucleus are
      present in interphase nuclei and are released into the ooplasm during nuclear
      envelope breakdown. Nucleoplasmin, which is synthesised in the cytoplasm and
      accumulated within the nucleus, is likely a major candidate for these factors.

PMID- 9652071
TI  - Promotion of follicular antrum formation by pig oocytes in vitro.
AB  - Pig oocyte-cumulus-granulosa cell complexes (OCG complexes) from pig early antral
      follicles reorganise an antrum under the stimulation of FSH. The purpose of this
      study was to examine the role of the oocytes in antrum formation. In the first
      experiment, oocyte-cumulus complexes were removed from pig OCG complexes, and the
      antrum formation of parietal granulosa cells themselves (PGs) was examined.
      Antrum formation by sham-operated OCG complexes (OC/G complexes), in which the
      connections between the oocytes-cumulus complexes and the parietal granulosa
      cells had been disrupted, was also examined. The complexes were cultured for 8
      days in collagen gels in the presence of 10 ng/ml FSH. Antra were formed in about
      60% of the intact OCG complexes and the sham-operated OCG complexes, while only
      20% of the PGs formed antra. In the second experiment, oocyte-cumulus complexes
      in the OCG complexes were replaced by denuded oocytes (O/G complexes) or Sephadex
      G-25 beads (B/G complexes) similar in diameter to the oocytes, and the two types
      of complexes were cultured under the same conditions. The O/G complexes formed
      antra to a similar extent as the OC/G complexes, whereas the B/G complexes
      scarcely formed any antra. The histological sections showed that the granulosa
      cells in the OC/G and O/G complexes were in intimate contact with each other and
      retained a shape similar to those in the ovarian follicles, while the granulosa
      cells in the PGs and B/G complexes became quite irregular in shape. These results
      suggest that pig oocytes promote contact between the granulosa cells to induce
      antrum formation in a physiological manner.

PMID- 9652072
TI  - Cortical granule exocytosis is triggered by different thresholds of calcium
      during fertilisation in sea urchin eggs.
AB  - In sea urchin eggs, fertilisation is followed by a calcium wave, cortical granule
      exocytosis and fertilisation envelope elevation. Both the calcium wave and
      cortical granule exocytosis sweep across the egg in a wave initiated at the point
      of sperm entry. Using differential interference contrast (DIC) microscopy
      combined with laser scanning confocal microscopy, populations of cortical
      granules undergoing calcium-induced exocytosis were observed in living urchin
      eggs. Calcium imaging using the indicator Calcium Green-dextran was combined with
      an image subtraction technique for visual isolation of individual exocytotic
      events. Relative fluorescence levels of the calcium indicator during the
      fertilisation wave were compared with cortical fusion events. In localised
      regions of the egg, there is a 6s delay between the detection of calcium release
      and fusion of cortical granules. The rate of calcium accumulation was altered
      experimentally to ask whether this delay was necessary to achieve a threshold
      concentration of calcium to trigger fusion, or was a time-dependent activation of
      the cortical granule fusion apparatus after the 'triggering' event. Calcium
      release rate was attenuated by blocking inositol 1,4,5-triphospate (InsP3)-gated
      channels with heparin. Heparin extended the time necessary to achieve a minimum
      concentration of calcium at the sites of cortical granule exocytosis. The data
      are consistent with the conclusion that much of the delay observed normally is
      necessary to reach threshold concentration of calcium. Cortical granules then
      fuse with the plasma membrane. Further, once the minimum threshold calcium
      concentration is reached, cortical granule fusion with the plasma membrane occurs
      in a pattern suggesting that cortical granules are non-uniform in their calcium
      sensitivity threshold.

PMID- 9652073
TI  - Nuclear envelope removal/maintenance determines the structural and functional
      remodelling of embryonic red blood cell nuclei in activated mouse oocytes.
AB  - Nuclei of embryonic red blood cells (e-RBC) from 12-day mouse fetuses are
      arrested in G0 phase of the cell cycle and have low transcriptional activity.
      These nuclei were transferred with help of polyethylene glycol (PEG)-mediated
      fusion to parthenogenetically activated mouse oocytes and heterokaryons were
      analysed for nuclear structure and transcriptional activity. If fusion proceeded
      25-45 min after oocyte activation, e-RBC nuclei were induced to nuclear envelope
      breakdown and partial chromatin condensation, followed by formation of nuclei
      structurally identical with pronuclei. These 'pronuclei', similar to egg (female)
      pronuclei, remained transcriptionally silent over several hours of in vitro
      culture. If fusion was performed 1 h or later (up to 7 h) after activation, the
      nuclear envelope of e-RBC nuclei remained intact and nuclear remodelling was less
      spectacular (slight chromatin decondensation, formation of nucleolus precursor
      bodies). These nuclei, however, reinforced polymerase-II-dependent transcription
      within a few hours of in vitro culture. Our present experiments, together with
      our previous work, demonstrate that nuclear envelope breakdown/maintenance are
      critical events for nuclear remodelling in activated mouse oocytes and that
      somatic dormant nuclei can be stimulated to renew transcription at a time when
      the female pronucleus remains transcriptionally silent.

PMID- 9652074
TI  - The polysulphate binding domain of human proacrosin/acrosin is involved in both
      the enzyme activation and spermatozoa-zona pellucida interaction.
AB  - Mammalian acrosin is a protease present as a zymogen in the acrosome of a non
      reacted mammalian sperm, and in vitro is able to carry out limited hydrolysis of
      homologous and heterologous zonae pellucidae. On the other hand, sulphated
      polymers and zona pellucida glycoproteins bind to acrosin on a domain different
      from the active site, named the polysulphate binding domain (PSBD). Thus it is
      believed that acrosome-reacted spermatozoa bind to glycan chains of the zona
      pellucida through PSBD participating as secondary binding receptor. The aim of
      the present work was to study the role of PSBD during both human gamete
      interaction and acrosin activation. In this work we present evidence that the
      anti-human acrosin monoclonal antibody C5F10 is directed to an epitope located on
      or near the PSBD on human proacrosin/acrosin. Moreover, we show that this
      antibody is able to inhibit both proacrosin activation induced by fucoidan and
      the sperm binding to the zona pellucida. Our results suggest that the same PSBD
      is involved in both sperm secondary binding, during zona pellucida penetration,
      and proacrosin activation.

PMID- 9652075
TI  - Voltage-gated calcium channels in Pleurodeles oocytes: classification, modulation
      and functional roles.
AB  - In unfertilised Pleurodeles oocytes, two distinct types of high voltage-activated
      Ca2+ channels are expressed: a slowly inactivating Ca2+ channel and a transient
      one. The first is dihydropyridine-sensitive and is referred to as the L-type Ca2+
      channel. The transient channel is highly sensitive to Ni2+. Phosphorylation
      through protein kinases G and A facilitates and inhibits the L-type Ca2+ channel
      respectively. The transient type channel is insensitive to stimulation by protein
      kinases (A and G). The functional expression of L-type and transient Ca2+
      channels is modulated by the two maturation seasons. The transient Ca2+ currents
      are only observed during the resting season, while the L-type current is observed
      either alone during the breeding season or in association with the transient
      current during the resting season. Moreover, the current density of the L-type
      Ca2+ channel is much greater during the breeding season than the resting season.
      Thus, the wide distribution of L-type Ca2+ channels in Pleurodeles oocytes during
      the two seasons suggests that the roles of these channels may be important in the
      regulation of the maturation process.

PMID- 9652076
TI  - An olfactory neuronal network for vapor recognition in an artificial nose.
AB  - Odorant sensitivity and discrimination in the olfactory system appear to involve
      extensive neural processing of the primary sensory inputs from the olfactory
      epithelium. To test formally the functional consequences of such processing, we
      implemented in an artificial chemosensing system a new analytical approach that
      is based directly on neural circuits of the vertebrate olfactory system. An array
      of fiber-optic chemosensors, constructed with response properties similar to
      those of olfactory sensory neurons, provide time-varying inputs to a computer
      simulation of the olfactory bulb (OB). The OB simulation produces spatiotemporal
      patterns of neuronal firing that vary with vapor type. These patterns are then
      recognized by a delay line neural network (DLNN). In the final output of these
      two processing steps, vapor identity is encoded by the spatial patterning of
      activity across units in the DLNN, and vapor intensity is encoded by response
      latency. The OB-DLNN combination thus separates identity and intensity
      information into two distinct codes carried by the same output units, enabling
      discrimination among organic vapors over a range of input signal intensities. In
      addition to providing a well-defined system for investigating olfactory
      information processing, this biologically based neuronal network performs better
      than standard feed-forward neural networks in discriminating vapors when small
      amounts of training data are used.

PMID- 9652077
TI  - Reduction of a model for an Onchidium pacemaker neuron.
AB  - The eight-variable model for the giant neuron localized in the esophageal ganglia
      of the marine pulmonate mollusk Onchidium verruculatum is reduced to four- and
      three-dimensional systems by regrouping variables with similar time scales. These
      reduced models replicate the complex behavior including beating, periodic
      bursting and aperiodic bursting displayed by the original full model when the
      parameter Iext representing the intensity of the constant DC current stimulation
      is varied across a wide range. The complex behavior of the full model arises from
      the interaction of fast and slow dynamics, and depends on the time scale Cs of
      the slow dynamics. The four-variable reduced model is constructed independently
      from the parameter Cs so that it reproduces the two-dimensional bifurcation
      structure of the full model for the two parameters Iext and Cs. The three
      variable reduced model is derived for a specific value of Cs. The parameters of
      this model are tuned so that its one-parameter bifurcation diagram for Iext
      closely matches that of the full model. Correspondence between bifurcation
      structures ensures that both reduced models reproduce the various discharge
      patterns of the full model. Similarity between the full and reduced models is
      also confirmed by comparing mean firing frequencies and membrane potential
      waveforms in various regimes. The reduction exposes the factors essential for
      reproducing the dynamics of the full model; indeed, it shows that the eight
      variables representing the membrane potential and seven gating variables of six
      ionic currents in the full model account, in fact, for three basic processes
      responsible for excitability, post-discharge refractoriness and slow membrane
      modulation.

PMID- 9652078
TI  - Cortical memory dynamics.
AB  - Biological memories have a number of unique features, including (1) hierarchical,
      reciprocally interacting layers, (2) lateral inhibitory interactions within
      layers, and (3) Hebbian synaptic modifications. We incorporate these key features
      into a mathematical and computational model in which we derive and study Hebbian
      learning dynamics and recall dynamics. Introducing the construct of a feasible
      memory (a memory that formally responds correctly to a specified collection of
      noisy cues that are known in advance), we study stability and convergence of the
      two kinds of dynamics by both analytical and computational methods. A
      conservation law for memory feasibility under Hebbian dynamics is derived. An
      infomax net is one where the synaptic weights resolve the most uncertainty about
      a neural input based on knowledge of the output. The infomax notion is described
      and is used to grade memories and memory performance. We characterize the recall
      dynamics of the most favorable solutions from an infomax perspective. This
      characterization includes the dynamical behavior when the net is presented with
      external stimuli (noisy cues) and a description of the accuracy of recall. The
      observed richness of dynamical behavior, such as its initial state sensitivity,
      provides some hints for possible biological parallels to this model.

PMID- 9652079
TI  - Detecting multimodality in saccadic reaction time distributions in gap and
      overlap tasks.
AB  - In many cases the distribution of saccadic reaction times (SRT) deviates
      considerably from a unimodal distribution and may often exhibit several peaks. We
      present a statistical approach to determining the number and form of the
      individual peaks. The overall density of the reaction times fi(t), i = 1...M
      obtained in M different experiments with the same subject is described as the sum
      of K basis functions xk(t), k = 1...K with different weights and an error term. A
      change in the experimental conditions is assumed to cause a change in the
      weights, not in the basis functions. We minimize the square of the difference
      (measured data minus approximation), divided by the error of the data.
      Incrementing K step by step we determine the necessary number of basis functions.
      This method is applied to data of six subjects tested in different saccade tasks.
      We detect five different modes: two in the range 80-140 ms (express modes), two
      in the range 145-190 ms (fast-regular mode) and one at about 230 ms (slow-regular
      mode). These modes are located at about the same positions for different
      subjects. The method presented here not only proves statistically the existence
      of several modes in SRT distributions but also allows the distributions to be
      described by a few characteristic numbers that go beyond the mean values and
      standard deviations.

PMID- 9652080
TI  - Quantization of human motions and learning of accurate movements.
AB  - This paper presents a mathematical model for the learning of accurate human arm
      movements. Its main features are that the movement is the superposition of smooth
      submovements, the intrinsic deviation of arm movements is considered, visual and
      kinesthetic feed-back are integrated in the motion control, and the movement
      duration and accuracy are optimized with practice. This model is consistent with
      the jerky arm movements of infants, and may explain how the adult motion behavior
      emerges from the infant behavior. Comparison with measurements of adult movements
      shows that the kinematics of accurate movements are well predicted by the model.

PMID- 9652081
TI  - Standing sway: iterative estimation of the kinematics and dynamics of the lower
      extremities from force-plate measurements.
AB  - In this study, a model for the estimation of the dynamics of the lower
      extremities in standing sway from force plate data only is presented. A three
      dimensional, five-segment, four-joint model of the human body was used to
      describe postural standing sway dynamics. Force-plate data of the reactive forces
      and centers of pressure were measured bilaterally. By applying the equations of
      motion to these data, the transversal trajectory of the center of gravity (CG) of
      the body was resolved in the sagittal and coronal planes. An inverse kinematics
      algorithm was used to evaluate the kinematics of the body segments. The dynamics
      of the segments was then resolved by using the Newton-Euler equations, and the
      model's estimated dynamic quantities of the distal segments were compared with
      those actually measured. Differences between model and measured dynamics were
      calculated and minimized, using an iterative algorithm to re-estimate joint
      positioning and anthropometric properties. The above method was tested with a
      group of 11 able-bodied subjects, and the results indicated that the relative
      errors obtained in the final iteration were of the same order of magnitude as
      those reported for closed loop problems involved in direct kinematic measurements
      of human gait.

PMID- 9652082
TI  - Cyclic AMP oscillations in Dictyostelium discoideum: models and observations.
AB  - Oscillations in intra- and extracellular cyclic AMP are believed to underlie
      aggregation and morphogenesis in Dictyostelium discoideum. Upon comparing
      mathematical models with observations we find that the models are, qualitatively
      speaking, quite successful. At the same time many features remain unexplained. A
      strong case can be made for cyclic AMP-independent oscillations whose basis
      remains to be explored.

PMID- 9652083
TI  - Modeling oscillations and waves of cAMP in Dictyostelium discoideum cells.
AB  - We examine the theoretical aspects of temporal and spatiotemporal organization in
      the cAMP signaling system of Dictyostelium discoideum amoebae which aggregate in
      a wavelike manner after starvation, in response to pulses of cAMP emitted with a
      periodicity of several minutes by cells behaving as aggregation centers. We first
      extend the model based on receptor desensitization, previously proposed by
      Martiel and Goldbeter, by incorporating the role of G proteins in signal
      transduction. The extended model accounts for observations on the response of the
      signaling system to successive step increases in extracellular cAMP. In the
      presence of the positive feedback loop in cAMP synthesis, this model generates
      sustained oscillations in cAMP and in the fraction of active cAMP receptor,
      similar to those obtained in the simpler model where the role of the G proteins
      is not taken into account explicitly. We use the latter model to address the
      formation of concentric and spiral waves of cAMP in the course of D. discoideum
      aggregation. Previous analyses of the model showed that a progressive increase in
      the activity of adenylate cyclase and phosphodiesterase can account for the
      transitions no relay-relay-oscillations-relay observed in the experiments. We
      show that the degree of cellular synchronization on such a developmental path in
      parameter space markedly affects the nature of the spatial patterns generated by
      the model. These patterns range from concentric waves to a small number of large
      spirals, and finally to a large number of smaller spirals, as the degree of
      developmental desynchronization between cells increases.

PMID- 9652084
TI  - Propagating waves control Dictyostelium discoideum morphogenesis.
AB  - The morphogenesis of Dictyostelium results from the coordinated movement of
      starving cells to form a multicellular aggregate (mound) which transforms into a
      motile slug and finally a fruiting body. Cells differentiate in the mound and
      sort out to form an organised pattern in the slug and fruiting body. During
      aggregation, cell movement is controlled by propagating waves of the chemo
      attractant cAMP. We show that mounds are also organised by propagating waves.
      Their geometry changes from target or single armed spirals during aggregation to
      multi-armed spiral waves in the mound. Some mounds develop transiently into rings
      in which multiple propagating wave fronts can still be seen. We model cell
      sorting in the mound stage assuming cell type specific differences in cell
      movement speed and excitability. This sorting feeds back on the wave geometry to
      generate twisted scroll waves in the slug. Slime mould morphogenesis can be
      understood in terms of wave propagation directing chemotactic cell movement.

PMID- 9652085
TI  - Traveling waves in yeast extract and in cultures of Dictyostelium discoideum.
AB  - Biological self-organization was investigated in a biochemical and a cellular
      system: yeast extract and cultures of the slime mold Dictyostelium discoideum. In
      both systems traveling reaction-diffusion waves occur in response to oscillatory
      reactions. Glycolytic degradation of sugar in a yeast extract leads to the
      spontaneous formation of NADH and proton waves. Manipulation of the adenine
      nucleotide pool by addition of purified plasma membrane ATPase favors the
      formation of both reaction-diffusion waves and phase waves. The results indicate
      that the energy charge has an important impact for the dynamics of glycolytic
      patterns. When affecting the lower part of glycolysis by pyruvate addition the
      frequency of wave generation was increased with concomitant formation of rotating
      NADH and proton spirals. During morphogenesis of the cellular system
      Dictyostelium discoideum, circular and spiral shaped aggregation patterns of
      motile amoeboid cells form in response to traveling cAMP waves. Velocity analysis
      of the cell movements reveals that the cAMP waves guide the cells towards the
      site of wave initiation along optimized trajectories. The minimization of
      aggregation paths is based on a mechanism exploiting general properties of
      excitation waves. The resulting aggregation territories are reminiscent of
      Voronoi diagrams.

PMID- 9652086
TI  - Self-organizing molecular networks.
AB  - Strong diffusional mixing and short delivery times typical for micrometer and sub
      micrometer reaction volumes lead to a special situation where the turnover times
      of individual enzyme molecules become the largest characteristic time scale of
      the chemical kinetics. Under these conditions, populations of cross-regulating
      allosteric enzymes form molecular networks that exhibit various kinds of self
      organized coherent collective dynamics.

PMID- 9652087
TI  - Spark-to-wave transition: saltatory transmission of calcium waves in cardiac
      myocytes.
AB  - Using a modular approach, in which kinetic models of various mechanisms of
      calcium handling in cells are fine-tuned to in vivo and in vitro measurements
      before combining them into whole-cell models, three distinct modes of
      transmission of calcium waves in mature and immature frog eggs have been defined.
      Two modes of transmission are found in immature eggs, where the inositol 1,4,5
      trisphosphate receptor (IP3R) controls release of calcium from the endoplasmic
      reticulum (ER). The first mode corresponds to an excitable physiological state of
      the cytoplasm and results in solitary waves that can appear as circular or spiral
      waves in two dimensions with the wave speed proportional to the square root of
      the diffusion constant of calcium. A second mode occurs when the state of the
      cytoplasm is oscillatory and because of the small size of the buffered diffusion
      constant for calcium, the wave speed can appear to be weakly dependent on
      diffusion. In the mature frog egg, where the sperm-induced Ca2+ fertilization
      wave is a propagating front, the cytoplasm appears to be bistable and in this
      mode the wave speed is also proportional to the square root of the diffusion
      constant. Here we investigate a fourth mode of propagation for cardiac myocytes,
      in which calcium release from the sarcoplasmic reticulum (SR) is dominated by
      clusters of ryanodine receptors spaced at regular intervals. In myocytes a
      stochastically excitable myoplasm leads to the spontaneous production of calcium
      'sparks' that under certain conditions can merge into saltatory waves with a
      speed proportional to the diffusion constant.

PMID- 9652088
TI  - Calcium waves and oscillations driven by an intercellular gradient of inositol
      (1,4,5)-trisphosphate.
AB  - In response to a local mechanical stimulus, mixed glial cells initially exhibit a
      propagating intercellular Ca2+ wave. Subsequently, cells within a zone, at a
      specific distance from the stimulated cell, display asynchronous intracellular
      Ca2+ oscillations. The experimental hypothesis that the initial Ca2+ wave could
      be mediated by the passive diffusion of inositol (1,4,5)-trisphosphate (IP3) from
      the stimulated cell has been verified by model simulations. Further simulations
      with the same model also show that Ca2+ oscillations can only occur within model
      cells when the IP3 concentration is within a specific range. Thus, this passive
      diffusion model predicts (a) that the IP3 concentration gradient established in
      the cells following mechanical stimulation will initiate Ca2+ oscillations in
      cells in a specific zone along this gradient and (b) that different Ca2+
      oscillatory patterns will occur within a specified oscillatory zone. Both of
      these predictions have been confirmed by experimental data. The failure of
      experimentally observed Ca2+ oscillations to approach synchrony or entrain
      indicates a low intercellular calcium permeability of about 0.1 micron/s, and
      further suggests that Ca2+ does not appear to act as a significant messenger in
      the initiation of these intercellular Ca2+ waves or oscillations. In conclusion a
      passive diffusion of IP3, but not Ca2+, through gap junctions remains the
      preferred hypothesis for the mechanism underlying mechanically-stimulated
      intercellular calcium waves and Ca2+ oscillations.

PMID- 9652089
TI  - A model of mitochondrial Ca(2+)-induced Ca2+ release simulating the Ca2+
      oscillations and spikes generated by mitochondria.
AB  - Recent evidence underlines a key role of mitochondrial Ca2+ fluxes in cell Ca2+
      signalling. We present here a kinetic model simulating the Ca2+ fluxes generated
      by mitochondria during mitochondrial Ca(2+)-induced Ca2+ release (mCICR)
      resulting from the operation of the permeability transition pore (PTP). Our model
      connects the Ca2+ fluxes through the ruthenium redsensitive Ca2+ uniporter, the
      respiration-dependent and passive H+ fluxes, the rate of oxygen consumption, the
      movements of weak acids across the mitochondrial membrane, the electrical
      transmembrane potential (delta psi), and operation of the PTP. We find that two
      factors are crucial to account for the various mCICR profiles that can be
      observed experimentally: (i) the dependence of PTP opening and closure on matrix
      pH (pHi), and (ii) the relative inhibition of the respiratory rate consecutive to
      PTP opening. The resulting model can simulate irreversible Ca2+ efflux from
      mitochondria, as well as the genesis of damped or sustained Ca2+ oscillations,
      and of single Ca2+ spikes. The model also simulates the main features of mCICR,
      i.e. the threshold-dependence of mCICR triggering, and the all-or-nothing nature
      of mCICR operation. Our model should appear useful to further mathematically
      address the consequences of mCICR on the spatiotemporal organisation of Ca2+
      signals, as a 'plug-in' module for the existing models of cell Ca2+ signalling.

PMID- 9652090
TI  - Ca2+ wave dispersion and spiral wave entrainment in Xenopus laevis oocytes
      overexpressing Ca2+ ATPases.
AB  - Complex, spatiotemporal patterns of intracellular Ca2+ release in Xenopus oocytes
      can be accounted for by the operation of two fundamental processes: Ca2+ release
      from the endoplasmic reticulum (ER) via the inositol 1,4,5-trisphosphate receptor
      (IP3R) with its inherent dependency on cytosolic Ca2+, and Ca2+ uptake via Ca2+
      ATPases. Overexpression of sarco-endoplasmic reticulum Ca2+ ATPases (SERCAs) in
      Xenopus oocytes, increases IP3-induced Ca2+ wave frequency and amplitude [1-3].
      This effect can be attributed to an increased removal of cytoplasmic Ca2+ and
      more efficient refilling of Ca2+ stores. By overexpressing SERCA isoforms, we
      report here that Ca2+ waves exhibit dispersion [4-6]. At wavelengths greater than
      60 microns, wave velocity is constant. However, wave velocity and amplitude
      progressively decreases at smaller wavelengths. Below gamma approximately 20
      microns, Ca2+ waves disperse and fail to propagate. In oocytes exhibiting both
      spiral and target patterns of Ca2+ release, spiral waves had higher frequencies
      and showed entrainment of the surrounding regions. These properties are
      characteristic of a classical excitable medium [4-6].

PMID- 9652091
TI  - Role of calcium oscillations in mammalian egg activation: experimental approach.
AB  - Biological rhythms are everywhere; the pulsatility of intracellular signals
      appears to maximise the cellular processes better than constant signaling. The
      aim of this paper is, firstly, to review the cellular mechanisms that modulate
      calcium oscillator activity during fertilisation and, secondly, to describe
      recent results we have obtained by artificially imposing rhythmical calcium
      stimulation on fertilised rabbit eggs during in vitro culture. The key finding in
      these experiments is that the egg appears to be sensitive to repetitive
      signalling during a period that goes far beyond the time of meiosis reinitiation.
      When delivered at the proper rhythm transient signalling can optimise
      developmental processes.

PMID- 9652092
TI  - Link between fertilization-induced Ca2+ oscillations and relief from metaphase II
      arrest in mammalian eggs: a model based on calmodulin-dependent kinase II
      activation.
AB  - Mammalian eggs are ovulated in metaphase II of meiosis, in a state characterized
      by high levels of cyclin B and of active maturation promoting factor (MPF). This
      arrest is mediated by an activity referred to as cytostatic factor (CSF) which
      prevents the degradation of cyclin. Fertilization triggers a train of Ca2+ spikes
      which is responsible for the decrease in activity of both MPF and CSF. The
      decline in MPF however much precedes that in CSF. Experimental observations on
      mammalian eggs indicate that the kinetics of cell cycle resumption much depends
      on the temporal pattern of the repetitive Ca2+ spikes. Here, we propose a
      theoretical model which accounts for Ca(2+)-induced relief from metaphase II
      arrest in mammalian eggs. The model is based on the fact that Ca2+/calmodulin
      kinase II (CaMKII) activation is the primary event leading to inactivation of
      both CSF and MPF. To account for experimental observations, it has to be assumed
      that CaMKII activation affects the level of the active form of the anaphase
      promoting complex (APC), which initiates the degradation of cyclin, through two
      pathways characterized by different time scales. Thus, we hypothesize that CaMKII
      activation by Ca2+ leads to the transformation of a mediator protein from a form
      which stimulates the inactivation of the APC into a form which gradually and
      indirectly induces the deactivation of CSF. In consequence, a sufficient number
      of Ca2+ spikes first triggers the decrease of MPF, thus allowing the egg to enter
      in interphase, and later that of CSF. Finally, when CSF is low and when Ca2+
      oscillations have stopped, the level of MPF can increase again, a phenomenon that
      would correspond to the first mitosis. This model also accounts for the observed
      dependence of the time of entry in interphase (marked by the appearance of the
      pronuclei) on the frequency of Ca2+ spikes, as well as for the possible entry in
      metaphase III arrest, a pathological state of the egg which results from an
      insufficient activation by Ca2+. This study provides some theoretical prediction
      as to the time of the first mitosis as a function of the temporal pattern of Ca2+
      oscillations.

PMID- 9652093
TI  - Modeling M-phase control in Xenopus oocyte extracts: the surveillance mechanism
      for unreplicated DNA.
AB  - Alternating phases of DNA synthesis and mitosis, during the first 12 cell
      divisions of frog embryos, are driven by autonomous cytoplasmic oscillations of M
      phase promoting factor (MPF). Cell-free extracts of frog eggs provide a
      convenient preparation for studying the molecular machinery that generates MPF
      oscillations and the surveillance mechanism that normally prevents entry into
      mitosis until chromosomal DNA is fully replicated. Early experiments suggested
      that unreplicated DNA blocks MPF activity by inducing phosphorylation of a
      crucial tyrosine residue, but recent evidence implicates a stoichiometric
      inhibitor (an MPF binding protein) as the 'braking' agent. Using a realistic
      mathematical model of the mitotic control system in frog egg extracts, we suggest
      that both tyrosine phosphorylation and a stoichiometric inhibitors are involved
      in the block of MPF by unreplicated DNA. Both pathways operate by raising the
      cyclin threshold for MPF activation. As a bonus, in the process of analyzing
      these experiments, we obtain more direct and reliable estimates of the rate
      constants in the model.

PMID- 9652094
TI  - Mathematical model of the fission yeast cell cycle with checkpoint controls at
      the G1/S, G2/M and metaphase/anaphase transitions.
AB  - All events of the fission yeast cell cycle can be orchestrated by fluctuations of
      a single cyclin-dependent protein kinase, the Cdc13/Cdc2 heterodimer. The G1/S
      transition is controlled by interactions of Cdc13/Cdc2 and its stoichiometric
      inhibitor, Rum1. The G2/M transition is regulated by a kinase-phosphatase pair,
      Wee1 and Cdc25, which determine the phosphorylation state of the Tyr-15 residue
      of Cdc2. The meta/anaphase transition is controlled by interactions between
      Cdc13/Cdc2 and the anaphase promoting complex, which labels Cdc13 subunits for
      proteolysis. We construct a mathematical model of fission yeast growth and
      division that encompasses all three crucial checkpoint controls. By numerical
      simulations we show that the model is consistent with a broad selection of cell
      cycle mutants, and we predict the phenotypes of several multiple-mutant strains
      that have not yet been constructed.

PMID- 9652095
TI  - Multiple attractors in immunology: theory and experiment.
AB  - This selective survey discusses the relative merits of various modeling
      approaches in immunology that exhibit multiple attractors, and also assesses the
      ability of the different models to contribute to deeper biological understanding.
      The first topic is global anti-idiotypic network models, which, like Hopfield
      neural network models, exhibit a large number of steady states that are
      identified with memory. It is shown that a 'reverse engineering approach' to T
      cell vaccination for autoimmunity, featuring steady states corresponding
      respectively to 'normality', 'vaccination' and 'disease', is able to spur new
      experiments, in spite of the model's deliberate neglect of almost all biological
      detail. Mention is made of several other T-cell models that feature bistability
      for Th1 or Th2 dominance, or for activation and unresponsiveness.

PMID- 9652096
TI  - Apyrase activity and platelet aggregation inhibitors in the tick Ornithodoros
      savignyi (Acari: Argasidae).
AB  - Ticks are ectoparasites that cause considerable damage to their hosts while
      feeding. The feeding process is facilitated by anti-haemostatic factors present
      in the tick saliva. Apyrase (ATP diphosphohydrolase, EC 3.6.1.5) is a platelet
      aggregation inhibitor found in most haematophagous organisms studied. The present
      study describes the identification and characterization of such an activity in
      the tick Ornithodoros savignyi. The enzyme conformed to many properties common to
      apyrases. These included a low substrate specificity, dependence on bivalent
      metal ions for activity and insensitivity to the classical ATPase inhibitors.
      Heat denaturation studies, pH optima and similar effects of inhibitors on the
      enzyme's ATP and ADP hydrolysing activitives supported its classification as an
      apyrase. Salivary gland extracts inhibited the platelet aggregation induced by
      ADP, collagen and thrombin and disaggregated aggregated platelets. The results
      suggest the presence of two or more anti-platelet factors present in the salivary
      glands of this tick species.

PMID- 9652097
TI  - Interstadial and infestation level-dependent variation in the transmission
      efficiency of Borrelia burgdorferi from mice to Ixodes ricinus ticks.
AB  - The efficiency with which the spirochaete Borrelia burgdorferi sensu stricto was
      transmitted from laboratory mice to larval and nymphal Ixodes ricinus ticks was
      assessed, using the polymerase chain reaction. The transmission efficiency to
      nymphs was significantly greater than to larvae when both fed together on the
      same host. Increased tick infestation levels of mice were correlated with
      significantly greater engorgement weights and higher B. burgdorferi transmission
      coefficients from mice to nymphs. These observations indicate that both the
      feeding success of ticks and the transmission coefficients from host to tick may
      be influenced by the tick infestation level of an infected host. The infestation
      level and the relative numbers of each life stage of the tick are factors which
      should be considered in the design of transmission experiments.

PMID- 9652098
TI  - Treatment of pica through multiple analyses of its reinforcing functions.
AB  - We conducted functional analyses of the pica of 3 participants. The pica of 1
      participant appeared to be maintained by automatic reinforcement; that of the
      other 2 participants appeared to be multiply controlled by social and automatic
      reinforcement. Subsequent preference and treatment analyses were used to identify
      stimuli that would complete with the automatic function of pica for the 3
      participants. These analyses also identified the specific aspect of oral
      stimulation that served as automatic reinforcement for 2 of the participants. In
      addition, functional analysis-based treatments were used to address the socially
      motivated components of 2 of the participants' pica. Results are discussed in
      terms of (a) the importance of using the results of functional analyses to
      develop treatments for pica and (b) the advantages of developing indirect
      analyses to identify specific sources of reinforcement for automatically
      reinforced behavior.

PMID- 9652099
TI  - Social interaction skills for children with autism: a script-fading procedure for
      beginning readers.
AB  - Engaging in spontaneous social exchanges is a central skill deficit of children
      with autism, and one that is often difficult to remediate. The 3 boys (ages 4, 4,
      and 5 years) who participated in this study had acquired small verbal
      repertoires, but typically spoke only when answering questions or requesting
      preferred edible items or toys, and did not converse with a familiar teacher
      during baseline. During teaching, textual cues ("Look" and "Watch me") were
      embedded in the youngsters' photographic activity schedules; after learning to
      use the scripts, the children's verbal elaborations and unscripted interactions
      increased and were maintained when a new recipient of interaction was introduced.
      After scripts were faded, unscripted interactions not only continued but also
      generalized to different activities that had not been the topic of teaching. The
      script-fading procedure enabled children with autism to converse with adults, to
      benefit from adults' language models, and to engage in language practice that
      contributes to fluency.

PMID- 9652100
TI  - Using a self-control training procedure to increase appropriate behavior.
AB  - The present study evaluated a technique for teaching self-control and increasing
      desirable behaviors among adults with developmental disabilities. Results showed
      that when participants were initially given the choice between an immediate
      smaller reinforcer and a larger delayed reinforcer, all participants repeatedly
      chose the smaller reinforcer. Concurrent fixed-duration/progressive-duration
      reinforcement schedules then were introduced in which initially both the smaller
      and larger reinforcers were available immediately. Thereafter, progressively
      increasing delays were introduced for the schedule associated with the larger
      reinforcer only. When initial short-duration requirements for access to the
      larger reinforcer were gradually increased, participants repeatedly selected the
      larger reinforcer, thereby demonstrating increased self-control.

PMID- 9652101
TI  - Effectiveness of functional communication training with and without extinction
      and punishment: a summary of 21 inpatient cases.
AB  - Functional communication training (FCT) is a frequently used treatment for
      reducing problem behavior exhibited by individuals with developmental
      disabilities. Once the operant function of problem behavior is identified by a
      functional analysis, the client is taught to emit an appropriate communicative
      response to obtain the reinforcer that is responsible for behavioral maintenance.
      Studies on FCT have typically used small numbers of participants, have reported
      primarily on clients for whom FCT was successful, and have varied with respect to
      their use of other treatment components. The main purposes of the present study
      were to evaluate the efficacy of FCT for treating severe problem behavior in a
      relatively large sample of individuals with mental retardation (N = 21) and to
      determine the contribution of extinction and punishment components to FCT
      treatment packages. FCT with extinction was effective in reducing problem
      behavior for the majority of clients and resulted in at least a 90% reduction in
      problem behavior in nearly half the applications. However, when demand or delay
      to-reinforcement fading was added to FCT with extinction, treatment efficacy was
      reduced in about one half of the applications. FCT with punishment (both with and
      without fading) resulted in at least a 90% reduction in problem behavior for
      every case in which it was applied.

PMID- 9652102
TI  - Visual identity matching and auditory-visual matching: a procedural note.
AB  - After preliminary computerized training on visual-visual identity matching, a 5
      year-old boy with autism (Sam) was given visual-visual and auditory-visual
      matching-to-sample tests with new stimuli. He did well in matching dictated name
      samples to 20 pictures, 26 printed upper case letters, and 9 single-digit
      numbers. In matching the visual stimuli (pictures, letters, or numbers) to
      themselves, however, he did not perform well. We then increased the number of
      picture comparisons per trial from two to three. In tests after this three
      comparison training, Sam correctly matched on 95% of the original 20-stimulus,
      four-comparison, identity-matching test trials. He went on to demonstrate
      accurate identity matching of the numbers, letters, and new pictures. In identity
      matching tests on the table top, he performed poorly until the stimulus array was
      made to resemble the stimulus arrangement on the computer. These findings showed
      that seemingly small procedural changes can influence performance and
      demonstrated that successful auditory-visual matching does not guarantee
      proficiency in visual-visual identity matching.

PMID- 9652103
TI  - Identifying work preferences among individuals with severe multiple disabilities
      prior to beginning supported work.
AB  - We evaluated a prework assessment for predicting work-task preferences among
      workers with severe multiple disabilities prior to beginning supported work. The
      assessment involved comparing worker selections from pairs of work tasks drawn
      from their future job duties. Results of workers' choices once they began their
      jobs in a publishing company indicated that the assessment predicted tasks that
      the workers preferred to work on during their job routines. Results are discussed
      regarding other possible means of determining preferred types of supported work.

PMID- 9652104
TI  - Increasing compliance with medical procedures: application of the high
      probability request procedure to a toddler.
AB  - The effects of high-probability (high-p) requests on compliance with low
      probability (low-p) responses have received increased attention from applied
      investigators. This study examined the effects of a high-p procedure on a
      toddler's compliance with medical procedures. Compliance to low-p requests
      occurred more frequently following compliance to high-p requests, suggesting that
      this procedure may be useful across different topographies of compliance.

PMID- 9652105
TI  - A behavioral intervention for improving verbal behaviors of heroin addicts in a
      treatment clinic.
AB  - Positively reinforcing appropriate behaviors improved verbal behaviors of opioid
      dependent patients in a buprenorphine treatment clinic. During B phases of an
      ABAB design, clients received stickers for engaging in appropriate verbal or
      nonverbal behaviors. Each sticker provided a chance of winning $25. No
      reinforcement was provided during the A phases. Appropriate verbal behaviors
      increased during reinforcement periods, and inappropriate verbal behaviors
      decreased.

PMID- 9652106
TI  - Simplified habit reversal treatment for chronic hair pulling in three
      adolescents: a clinical replication with direct observation.
AB  - Three developmentally normal adolescents with chronic hair pulling were treated
      with a simplified habit reversal procedure consisting of awareness training,
      competing response training, and social support. Treatment resulted in an
      immediate reduction to near-zero levels of hair pulling, with one to three
      booster sessions required to maintain these levels. The results were maintained
      from 18 to 27 weeks posttreatment, although 1 participant reported difficulty at
      follow-up. The effectiveness of simplified habit reversal and suggestions for
      future research are discussed.

PMID- 9652107
TI  - Effects of immediate self-correction, delayed self-correction, and no correction
      on the acquisition and maintenance of multiplication facts by a fourth-grade
      student with learning disabilities.
AB  - This study compared the effects of immediate self-correction, delayed self
      correction, and no correction on the acquisition and maintenance of
      multiplication facts by a fourth-grade student with learning disabilities. Data
      from daily and maintenance tests indicated that both correct response rate and
      accuracy were higher when self-correction was immediate rather than delayed or
      absent.

PMID- 9652108
TI  - Effects of wrist weights on self-injurious and adaptive behaviors.
AB  - The effects of wrist weights on the self-injurious and adaptive behaviors of a
      young boy with profound mental retardation were evaluated. Application of wrist
      weights reduced SIB by 92% and was associated with either increases or stable
      levels of multiple novel and preexisting adaptive behaviors.

PMID- 9652109
TI  - Protein phosphorylation: technologies for the identification of phosphoamino
      acids.
AB  - Protein phosphorylation plays a central role in many biological and biomedical
      phenomena. In this review, while a brief overview of the occurrence and function
      of protein phosphorylation is given, the primary focus is on studies related to
      the detection and analysis of phosphorylation both in vivo and in vitro. We focus
      on phosphorylation of serine, threonine and tyrosine, the most commonly
      phosphorylated amino acids in eukaryotes. Technologies such as radiolabelling,
      antibody recognition, chromatographic methods (HPLC, TLC), electrophoresis, Edman
      sequencing and mass spectrometry are reviewed. We consider the speed, simplicity
      and sensitivity of tools for detection and identification of protein
      phosphorylation, as well as quantitation and site characterisation. The
      limitations of currently available methods are summarised.

PMID- 9652110
TI  - Protein binding on polyelectrolyte-treated glass. Effect of structure of adsorbed
      polyelectrolyte.
AB  - Polyelectrolyte adsorption can be used to modify the surface of chromatographic
      packings in order to make them more suitable for protein separations. We studied
      the binding of proteins to controlled pore glass (CPG) on which the polycation
      poly(diallyldimethylammonium chloride) (PDADMAC) was noncovalently immobilized
      through electrostatic interaction. We found that the selectivity of PDADMAC for
      bovine serum albumin vs. beta-lactoglobulin, identified in previous selective
      coacervation studies, is conserved after its immobilization on the CPG surface.
      Protein binding results showed that the pH, ionic strength, and mixing time for
      polyelectrolyte adsorption all affect subsequent protein binding, presumably via
      the molecular properties of the adsorbed polyelectrolyte layer. The
      polyelectrolyte adsorption layer thickness, for polyelectrolyte adsorbed at pH
      9.0, ionic strength I = 0.001, was measured with size-exclusion chromatography as
      delta H = 2.5 +/- 0.5 nm. Quasielastic light scattering measurement of the
      polyelectrolyte hydrodynamic layer thickness (HLT) with a model system of PDADMAC
      and silica, supported a correlation between the structure of the adsorbed
      polyelectrolyte layer (e.g., loops and tails) and subsequent protein binding,
      although differences in magnitude between delta H and HLT suggest that adsorption
      onto silica may not mimic adsorption on CPG.

PMID- 9652111
TI  - Toroidal coil counter-current chromatography. Achievement of high resolution by
      optimizing flow-rate, rotation speed, sample volume and tube length.
AB  - This paper deals with optimization of a new seal-free compact toroidal coil
      centrifuge to achieve high resolution in analytical counter-current
      chromatography (CCC). Toroidal coil CCC (hydrostatic motion) has advantages
      compared with high-speed CCC (efficiently mixing solution with planetary motion)
      in the separation of protein or easily emulsified samples. A toroidal coil
      separation column of 0.4 mm I.D. PTFE tubing was accommodated around the
      periphery of the cylindrical centrifuge bowl. Using a two-phase solvent system
      composed of chloroform-acetic acid-0.1 M hydrochloric acid (2:2:1, v/v/v) and a
      set of dinitrophenyl-amino acids as test samples, a series of experiments was
      performed with parameters such as the column length, sample volume, flow-rate,
      elution mode of the mobile phase and rotation speed. The highest efficiency, over
      10,000 theoretical plates, was achieved with a 100 m long coiled tube and an 11
      ml total capacity at a flow-rate of 0.01 ml/min at 800 rpm.

PMID- 9652112
TI  - Calculation of peptide retention coefficients in normal-phase liquid
      chromatography.
AB  - The retention of 121 peptides was studied on a TSK Amide-80 column using
      solutions containing 0.1% trifluoroacetic acid and an increasing linear gradient
      of water in acetonitrile. The contribution of each residue to retention was
      calculated by linear multiple regression analysis. This paper described the
      contribution values 'hydrophilicity retention coefficients'. The result is an
      index of hydrophilicity retention coefficients for normal-phase liquid
      chromatography, analogous to the hydrophobicity indices calculated for the
      reversed-phase liquid chromatography. The order of residues in the index of one
      mode was substantially the inverse of the others'. Using the new hydrophilicity
      retention coefficients, retention times could be predicted for peptides of known
      amino acid content and sequence.

PMID- 9652113
TI  - Retention behavior of D,L-dansyl-amino acids on a human serum albumin chiral
      stationary phase: effect of a mobile phase modifier.
AB  - The effect of perchlorate anion as a mobile phase modifier on the retention of
      dansyl norvaline and dansyl tryptophan enantiomers on a human serum albumin (HSA)
      column was studied by varying the chaotropic agent concentrations. The
      thermodynamic parameters for the transfer of a solute from the mobile to the HSA
      stationary phases were determined from linear van't Hoff plots. An enthalpy
      entropy compensation study revealed that the type of interaction between the
      solute and HSA was independent of the molecular structure. The parabolic
      variations observed with the enthalpic and entropic terms of dansyl amino acid
      transfer in relation to the concentration of perchlorate anion were considered to
      be the result of the change from reversed to normal-phase conditions for this
      chromatographic system.

PMID- 9652114
TI  - Rapid verification of disulfide linkages in recombinant human growth hormone by
      tandem column tryptic mapping.
AB  - An automated tryptic mapping method was developed for characterization of
      disulfide linkages in recombinant human growth hormone (rhGH). The hormone was
      trypsin digested and the peptide fragments concentrated by eluting rhGH through
      an immobilized trypsin column and transferring the peptides directly to a
      reversed-phase liquid chromatography (RP-LC) column where they were collected.
      Reaction time was controlled by the flow-rate. Following tryptic digestion of a
      sample, the immobilized enzyme column was uncoupled from the flow train by a
      switching valve and the RP-LC column eluted with a solvent gradient ranging from
      0.1% trifluoroacetic acid (TFA) with 1% acetonitrile (ACN) to ACN with 0.1% TFA
      and 5% water. This two-step mapping process was achieved within 2 h on both
      native and reduced rhGH samples. The chromatographic elution position and mass
      spectra matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry of native rhGH and sulfur-containing peptides were determined with
      standards. Standards of the individual sulfhydryl (-SH) containing peptides and
      all possible disulfide linked peptides that could result from coupling the -SH
      peptides in disulfide linkages were obtained by synthesis and chromatographic
      purification. This approach allowed the chromatographic elution position of all
      possible mismatched disulfide containing peptides to be established and samples
      of rhGH to be examined for improper folding.

PMID- 9652115
TI  - Hybrid affinity chromatography of alpha-galactosidase from Verbascum thapsus L.
AB  - Purification of alpha-galactosidase from the roots of Verbascum thapsus L. was
      difficult to achieve using conventional methods due to the presence of coloured
      contaminants. A newly developed procedure, hybrid affinity chromatography, which
      was based on a mixed matrix separation procedure, using a substrate analogue and
      an immobilized metal affinity matrix as ligands, respectively, allowed the
      purification of this enzyme with good recovery. The method should be applicable
      to other proteins as well.

PMID- 9652116
TI  - Preparative ion-exchange chromatography of proteins from dairy whey.
AB  - A preparative-scale ion-exchange chromatographic process is described for the
      separation of the four major proteins and lactose from sweet dairy whey.
      Experiments using a commercial anion-exchange resin were carried out to determine
      the optimum conditions for initially separating the proteins alpha-lactalbumin,
      beta-lactoglobulin, bovine serum albumin, immunoglobulin G and lactose from a
      sweet dairy whey mixture. The separation was accomplished with simultaneous step
      elution changes in salt concentration and pH. It was found that the anion
      exchange step was most effective in separating beta-lactoglobulin from the feed
      mixture. Following the anion-exchange separation, its breakthrough curve was
      processed using a commercial cation-exchange resin to further recover the
      valuable immunoglobulin G. The whey output from an east Tennessee cheese
      manufacturer was used as a feedstream for the preparative scale experiments and
      as a reference in scaling to an economically optimized production level
      operation.

PMID- 9652117
TI  - High-performance liquid chromatography of Pasteurella haemolytica leukotoxin
      using anion-exchange perfusion columns.
AB  - An exotoxin, called leukotoxin (LKT), from Pasteurella haemolytica, which had
      previously proved difficult to purify, was purified by high-performance liquid
      chromatography using rigid highly hydrophilic microparticulate anion-exchange
      columns. These anion-exchange stationary phases were employed to overcome
      difficulties of the relatively hydrophobic LKT interacting with dextran or
      styrene-based resins. While a short non-porous DEAE column allowed the partial
      microscale purification of the leukotoxin at pH 7.0, a high capacity strong anion
      exchange column of the perfusion chromatography type permitted the purification
      of LKT on a much larger scale. The purification of the LKT on the large pore
      strong anion-exchange perfusion column was best achieved when three consecutive
      linear gradients at increasing NaCl concentration in 20 mM Tris buffer, pH 8.0,
      containing 6.0 M urea and 0.25% Tween 20 were used. Under these conditions, a
      better separation was obtained for the tetrameric and aggregate peaks of LKT from
      the early eluting contaminant peaks. This separation scheme allowed good recovery
      of activity and purification of the LKT to near homogeneity.

PMID- 9652118
TI  - On-line preconcentration and determination of chromium(VI) in waters by high
      performance liquid chromatography using precolumn complexation with 1,5
      diphenylcarbazide.
AB  - A method for on-line chromatographic preconcentration and determination of
      chromium(VI) traces has been developed. Chromate was preconcentrated on a C18
      column (50 x 6 mm I.D.) after complexation with diphenylcarbazide (DPC).
      Following the preconcentration step, analysis of the sample was performed using a
      C18 column (100 x 6 mm I.D.) with an eluent containing 6.10(-3) mol/l sulphuric
      acid and 20% (v/v) acetonitrile. Direct spectrophotometric detection at 546 nm
      was used. Experimental parameters such as mobile phase pH, DPC concentration,
      preconcentration flow-rate, sample volume were optimized for preconcentration and
      detection of Cr(VI)-DPC complex. Under the optimum conditions, most metal ions
      [Cr(III), Fe(III), Cu(II), Hg(II), Mo(VI), V(V)] and inorganic anions did not
      interfere. A detection limit of 0.02 ng/ml Cr(VI) can be attained when a sample
      volume of 100 ml is used. The technique has been applied successfully to the
      determination of Cr(VI) traces in drinking, surface and groundwater samples and
      the recoveries of added chromium were in the range 94-104%.

PMID- 9652119
TI  - Headspace solid-phase microextraction analysis of volatile sulphides and
      disulphides in wine aroma.
AB  - Sulphur compounds (S-compounds) are important constituents of wine off-flavours.
      Headspace solid-phase microextraction (HS-SPME) combined with gas chromatography
      coupled to flame photometric detection (GC-FPD) was used to develop a suitable
      method to analyse volatile sulphides and disulphides. This is a very simple and
      fast technique which gives good reproducibility at microgram/l levels (relative
      standard deviations < 10%). The analytes were extracted from the headspace of the
      samples by using either polydimethylsiloxane or polyacrylate coated fused-silica
      fibers in an SPME unit. Then, the fiber was inserted into the injector of a gas
      chromatograph and the extracted S-compounds were thermally desorbed. The
      influence of different parameters, such as ionic strength, stirring, headspace
      volume, ethanol concentration, time and temperature of extraction, was studied.
      The extraction of the fibers varies considerably for the different sulphur
      compounds studied. The most volatile compounds were the least extracted by the
      coating fibers tested. The standard additions technique, applied to real samples,
      gave the recoveries > 94%. The detection limits range between 3 micrograms/l and
      50 ng/l. The overall process was successfully applied to identify and quantify S
      compounds in white and red wines.

PMID- 9652120
TI  - Capillary zone electrophoresis with indirect UV detection of haloacetic acids in
      water.
AB  - A capillary zone electrophoresis (CZE) system for determining haloacetic acids in
      water was optimized with indirect photometric detection. Two different carrier
      electrolytes, potassium hydrogenphthalate and sodium 2,6
      naphthalenedicarboxylate, were evaluated in terms of sensitivity and two
      different electroosmotic flow modifiers, tetradecyltrimethylammonium bromide and
      hexadecyltrimethylammonium bromide, were tested. Parameters such as electrolyte
      concentration and pH, and the concentration of the electroosmotic flow modifiers,
      which affect the CZE separations, were investigated. The method was used to
      determine haloacetic acids in chlorine tap water using the liquid-liquid
      extraction process.

PMID- 9652121
TI  - Separation of ergot alkaloids and their epimers and determination in sclerotia by
      capillary electrophoresis.
AB  - Capillary electrophoresis has been shown to be a very useful analysis technique
      for secondary metabolites of plants. In the present study a method is described
      for the qualitative and quantitative determination of ergot alkaloids and their
      epimers. The extraction from the biological matrix yields recoveries of 50-97%,
      depending on the individual alkaloid. Using a mixture of 20 mM beta-cyclodextrin
      (CD), 8 mM gamma-CD, 2 M urea and 0.3% (w/w) poly(vinyl alcohol) to phosphate
      buffer at pH 2.5 the simultaneous separation of all analytes was achieved. A 37
      cm (30 cm) fused-silica capillary, at a voltage of 25 kV and a temperature of 20
      degrees C, was used for the analysis. Overall analysis time for the separation
      was 12 min. The limit of detection of the alkaloids using UV detection at 214 nm
      can be improved 30-fold to about 9.10(-8) M when laser-induced fluorescence
      detection is applied.

PMID- 9652122
TI  - The manumycin-group metabolites.

PMID- 9652123
TI  - Steroids: reactions and partial synthesis.

PMID- 9652124
TI  - Biosynthesis of fatty acids and related metabolites.

PMID- 9652125
TI  - Following the invisible trail: kinematic analysis of mate-tracking in the copepod
      Temora longicornis.
AB  - We have analysed the fine-scale kinematics of movement of male and female
      copepods, Temora longicornis, to resolve how these small animals find their
      mates. Location of the trail initially involves rapid random turning and high
      rates of directional change. Males subsequently increase their rate of movement
      as they follow the trail, and execute a regular pattern of counter turns in both
      x,z and y,z planes to stay near or within the central axis of the odour field.
      Pursuit behaviour of males is strongly associated with female swimming behaviour,
      suggesting that quantifiable variations in the structure of the odour signal
      released by females affects male tracking. The behavioural components of mate
      tracking in Temora are very similar to those of other animals that employ
      chemically mediated orientation in their search for mates and food, and we
      conclude that male Temora find their mates using chemoperception. The kinematic
      analysis indicates both sequential and simultaneous taxis mechanisms are used by
      Temora to follow the odour signal. This, in turn, indicates that rather than
      responding to a diffuse plume, males are following a signal more accurately
      characterized as a chemical trail, and copepods appear to use mechanisms that are
      similar to those employed by trail-following terrestrial insects such as ants.
      While Temora expresses similar behaviours to those of a variety of chemosensory
      organisms, the ability to track a three-dimensional odour trail appears unique,
      and possibly depends on the persistence of fluid-borne odour signals created in
      low Reynolds number hydrodynamic regimes.

PMID- 9652126
TI  - The fluid physics of signal perception by mate-tracking copepods.
AB  - Within laboratory-induced swarms of the marine copepod Temora longicornis, the
      male exhibits chemically mediated trail-following behaviour, concluding with
      fluid mechanical provocation of the mate-capture response. The location and
      structure of the invisible trail were determined by examining the specific
      behaviour of the female copepods creating the signal, the response of the male to
      her signal, and the fluid physics of signal persistence. Using the distance of
      the mate-tracking male from the ageing trail of the female, we estimated that the
      molecular diffusion coefficient of the putative pheromonal stimulant was 2.7 x
      10(-5) cm2 s-1, or 1000 times slower than the diffusion of momentum. Estimates of
      signal strength levels, using calculations of diffusive properties of odour
      trails and attenuation rates of fluid mechanical signals, were compared to the
      physiological and behavioural threshold detection levels. Males find trails
      because of strong across-plume chemical gradients; males sometimes go the wrong
      way because of weak along-plume gradients; males lose the trail when the female
      hops because of signal dilution; and mate-capture behaviour is elicited by
      suprathreshold flow signals. The male is stimulated by the female odour to
      accelerate along the trail to catch up with her, and the boundary layer
      separating the signal from the chemosensitive receptors along the copepod
      antennule thins. Diffusion times, and hence reaction times, shorten and
      behavioural orientation responses can proceed more quickly. While 'perceptive'
      distance to the odour signal in the trail or the fluid mechanical signal from the
      female remains within 1-2 body lengths (< 5 mm), the 'reactive' distance between
      males and females was an order of magnitude larger. Therefore, when nearest
      neighbour distances are 5 cm or less, as in swarms of 10(4) copepods m-3, mating
      events are facilitated. The strong similarity in the structure of mating trails
      and vortex tubes (isotropic, millimetre-centimetre scale, 10:1 aspect ratio, 10s
      persistence), indicates that these trails are constrained by the same physical
      forces that influence water motion in a low Reynolds number fluid regime, where
      viscosity limits forces to the molecular scale. The exploratory reaches of mating
      trails appear inscribed within Kolmogorov eddies and may represent a measure of
      eddy size. Biologically formed mating trails, however, are distinct in their flow
      velocity and chemical composition from common small-scale turbulent features; and
      mechanoreceptive and chemoreceptive copepods use their senses to discriminate
      these differences. Zooplankton are not aimless wanderers in a featureless
      environment. Their ambit is replete with clues that guide them in their efforts
      for survival in the ocean.

PMID- 9652127
TI  - Mercury in water and sediments of the southern Baltic sea.
AB  - Total mercury concentrations [HgT] were measured in samples of water and
      sediments collected from the southern Baltic Sea from the period 1993-1995.
      Picomolar concentrations of HgT were found in offshore surface water. Higher
      levels were measured in samples from the plum of the Vistula. An exceptionally
      high concentration of mercury (25 pM HgT, 5 pM methylmercury) was measured in the
      near bottom, quasi-anoxic water of the Gdansk Deep and explained by the release
      of mercury from fine grained sediments covering the bottom. In the sediments, the
      largest contents of HgT were found in fine grained, organic rich deposits of the
      Baltic deeps. The increase in mercury contents in the upper layers of sediments
      deposited within the last 100-150 years was attributed to the anthropogenic load
      of mercury and its increased scavenging to sediments with organic matter.

PMID- 9652128
TI  - Mercury distribution in relation to iron and manganese in the waters of the St.
      Lawrence river.
AB  - Waters entering the St. Lawrence River from Lake Ontario and from the Ottawa
      River have been sampled on a quaternary basis between March 1995 and October
      1996. Mercury, iron, manganese, organic carbon and other chemical parameters have
      been determined in the filtered water (< 0.5 micron) and suspended particles (>
      0.5 micron). Average total mercury concentrations (+/- standard deviation, number
      of determinations) in filtered samples were 1.3 +/- 0.9 pM (39) at the mouth of
      Lake Ontario and 4.0 +/- 2.3 pM (54) at the outlet of the Ottawa River. The
      respective average concentrations in suspended particles were 1.1 +/- 0.4 (39)
      and 0.6 +/- 0.2 (55) nmol g-1. Partial correlation analyses reveal that in the
      fraction < 0.5 micron--which seems to consist of a significant fraction of
      colloids--mercury was significantly linked to iron, while in the particulate
      phase, mercury was related to manganese. Mercury was not correlated with organic
      carbon. A sorption model on iron and manganese hydroxides is proposed to explain
      these observations.

PMID- 9652129
TI  - An examination of spatial variation in mercury concentrations in otter (Lutra
      canadensis) in south-central Ontario.
AB  - Hair samples were collected from otter (Lutra canadensis) trapped in several
      parts of south-central Ontario, Canada. The concentrations of total Hg in hair
      were compared with methyl mercury concentrations in liver tissues from the same
      individuals to determine if hair is a suitable monitoring tissue. Hg in the two
      tissues was significantly correlated. Hair was used to monitor Hg in 51
      individuals from four townships. The concentrations of total Hg in hair ranged
      from 4 to 20 micrograms/g. No significant variation among the four sample regions
      existed. Generally the highest concentrations were found in the youngest members
      of the population. Some possible explanations for the observations are presented.

PMID- 9652130
TI  - Permanent impairment in the feeding behavior of grayling (Thymallus thymallus)
      exposed to methylmercury during embryogenesis.
AB  - Embryos of grayling (Thymallus thymallus) were exposed to different
      concentrations of methylmercury (0.16, 0.8, 4.0 and 20 micrograms Hg l-1) during
      the first 10 days of development. The exposure resulted in body concentrations in
      the newly hatched fry of 0.09, 0.27, 0.63 and 3.80 micrograms Hg g-1 wet wt.,
      respectively. A control group had a body concentration of 0.01 microgram Hg g-1.
      Morphological disturbances were only found in the highest exposure group. Three
      years later, at a size of 13.8 +/- 0.8 cm, the different groups were tested for
      sublethal toxicant effects on foraging behavior. In the first series of
      experiments we tested the foraging efficiency of the fish when kept alone for 5
      min in small flow-through aquariums. In the second series of experiments we
      tested the competitive ability of eight individuals from an exposed group vs.
      eight individuals from a control group when kept together for 30 min in a 300-1
      aquarium. In both experiments live Dapnia magna were used as prey. We found
      impaired feeding efficiencies and reduced competitive abilities in grayling from
      the exposed groups which as yolk-fry had Hg concentrations of 0.27 microgram g-1
      or more. In the foraging efficiency experiments these groups were 15-24% less
      efficient as compared to the control group. In the competitive ability
      experiments the control group caught two to six times as many preys as these
      exposed groups. Such harmful body concentrations of Hg (> 0.27 microgram g-1) may
      be found in eggs from piscivorous fishes in lakes receiving diffuse atmospheric
      depositions of mercury. We suggest such concentrations may have ecological
      consequences by reducing the fitness of the affected populations.

PMID- 9652131
TI  - Mercury in alligators (Alligator mississippiensis) in the southeastern United
      States.
AB  - Mercury methylation may be enhanced in wetlands and humic-rich, blackwater
      systems that crocodiles and alligators typically inhabit. Given their high
      trophic level and long life-spans, crocodilians could accumulate significant
      burdens of Hg. Our objectives were to survey Hg concentrations in alligators from
      several areas in the southeastern United States to test their utility as
      sentinels of Hg contamination, to examine relationships among Hg concentrations
      in various tissues and to look for any differences in tissue Hg concentrations
      among locations. We measured total Hg concentrations in alligators collected in
      the Florida Everglades (n = 18), the Okefenokee National Wildlife Refuge, Georgia
      (n = 9), the Savannah River Site (SRS), South Carolina (n = 49) and various
      locations in central Florida (n = 21), sampling tissues including blood, brain,
      liver, kidney, muscle, bone, fat, spleen, claws and dermal scutes. Alligators
      from the Everglades were mostly juvenile, but Hg concentrations in tissues were
      high (means: liver 41.0, kidney 36.4, muscle 5.6 mg Hg/kg dry wt.).
      Concentrations in alligators from other locations in Florida were lower (means:
      liver 14.6, kidney 12.6, muscle 1.8 mg Hg/kg dry wt.), although they tended to be
      larger adults. Alligators from the Okefenokee were smallest and had the lowest Hg
      concentrations (means: liver 4.3, kidney 4.8, muscle 0.8 mg Hg/kg dry wt.). SRS
      alligators had the greatest size range and intermediate Hg levels (means: liver
      14.9, muscle 4.8 mg Hg/kg dry wt.). At some locations, alligator length was
      correlated with Hg concentrations in some internal organs. However, at three of
      the four locations, muscle Hg was not related to length. Tissue Hg concentrations
      were correlated at most locations however, claw or dermal scute Hg explained less
      than 74% of the variation of Hg in muscle or organs, suggesting readily-obtained
      tissues, such as scutes or claws, have limited value for non-destructive
      screening of Hg in alligator populations.

PMID- 9652132
TI  - Mercury in a widely consumed fish Micropogonias furnieri (Demarest, 1823) from
      four main Brazilian estuaries.
AB  - We analyzed mercury levels in the white muscular tissue of a fish (Micropogonias
      furnieri) originated from four Brazilian estuaries during the period between the
      summer 1990 and spring 1991. Mercury levels were below the maximum permissible
      limit established for food by the Brazilian legislation (500.0 ng.g-1 wet wt.).
      The measured mercury concentrations ranged from 17.4 to 266.0 ng.g-1 (wet wt.),
      for Guanabara Bay 19.5-252.2 ng.g-1 (wet wt.), for Sepetiba Bay 23.0-433.7 ng.g-1
      (wet wt.), for Ilha Grande Bay 13.8-296.3 ng.g-1 (wet wt.) for Conceicao Lagoon.
      Positive relationships were observed between mercury concentration in fish and
      the length and weight of the fishes. Weight normalized concentration showed
      Guanabara Bay presented the higher levels and the Conceicao Lagoon presented the
      lowest levels. Ilha Grande Bay presented the second highest levels after Sepetiba
      Bay, although the former is considered a non-contaminated area.

PMID- 9652133
TI  - Development of fish mercury concentrations in Finnish reservoirs from 1979 to
      1994.
AB  - Mercury (Hg) concentrations in burbot (Lota lota), perch (Perca fluviatilis),
      northern pike (Esox lucius), roach (Rutilus rutilus), whitefish (Coregonus
      lavaretus) and peled (C. peled) were monitored in 18 reservoirs situated in
      western and northern Finland over a period of 16 years (1979-1994). The
      reservoirs were impounded from 1964 to 1980. The surface areas ranged between 1
      and 417 km2. Data from downstream sites and reference lakes were compared to
      reservoir mercury data. Generally, fish Hg concentrations in reservoirs exceeded
      those in natural lakes. Shortly after inundation, fish mercury concentrations
      clearly increased and remain 15-25 years above background concentrations. The
      mean Hg concentrations in standardized 1 kg pike from 1989 to 1993 was 0.45 mg/kg
      in natural lakes and 0.58 mg/kg in reservoirs. The 1 mg/kg fish Hg level
      recommended by health authorities as the upper limit for human consumption was
      still exceeded in two reservoirs 20 years old or more. The two largest reservoirs
      (24 and 27 years old in 1994) with significant commercial fishing had Hg levels
      below 0.5 mg/kg in all fish species studied. Statistical models for predicting
      the Hg concentrations in the weight standardized pike were verified with the
      observed data. For most of the reservoirs, predictions from models based on pH,
      organic matter (COD) in water, the extent of water level regulation and reservoir
      age agreed well with observed data. In the most southern, new (under 20 years
      old) and heavily regulated reservoirs, pike Hg concentration followed a
      logarithmic function of reservoir age. Model predictions of mercury in pike in
      the planned Vuotos reservoir (in northern Finland) predicted that Hg would exceed
      1 mg/kg Hg for the first 12 years after the flooding.

PMID- 9652135
TI  - The development of bioengineered skin.
AB  - Driven by the need for donor tissue for patients suffering from extensive burns,
      alternatives to autologous and cadaver-derived tissue have been under development
      for the past 20 years. Unilayered and bilayered models representing the skin's
      epidermal and/or dermal components have been developed using both cells and
      matrix materials. In addition to their use in patients with extensive burns,
      trials using these products on refractory and challenging patients with both
      acute and chronic wounds have led to the commercial availability of some of these
      products.

PMID- 9652134
TI  - The Trimera mouse: generating human monoclonal antibodies and an animal model for
      human diseases.
AB  - Monoclonal antibodies of human origin may have great therapeutic value in the
      treatment of cancer, autoimmune disorders and viral or bacterial infections.
      Several methods for generating human monoclonal antibodies exist; some are based
      on the transplantation of a functioning human immune system into severe combined
      immunodeficient (scid) mice or into Trimera mice, which are mice that have been
      lethally irradiated and radioprotected by transplantation of bone-marrow cells
      from scid mice. Trimera mice could be also used to develop animal models for
      human diseases by transplanting infected human tissue fragments and for creating
      models for cell therapy.

PMID- 9652136
TI  - Current trends in 'artificial-nose' technology.
AB  - Basic principles derived from biological olfaction, such as combining
      semiselective sensor arrays with pattern recognition, have been used to develop
      instrumentation capable of broad-band chemical detection and quantification.
      Commercially available instruments are useful in areas including quality control
      in the food, beverage and fragrance industries, environmental monitoring,
      chemical-purity and -mixture analysis, and medical diagnostics. Ongoing research
      is aimed at the development of more-advanced instruments that are smaller,
      cheaper, faster and more stable and reliable. These second-generation instruments
      are likely to find an increasing number of applications, including the on-line
      monitoring of fermentation and other bioprocesses.

PMID- 9652137
TI  - Hybrid enzymes: manipulating enzyme design.
AB  - Hybrid enzymes are engineered to contain elements of two or more enzymes. Hybrid
      enzyme approaches, by taking advantage of the vast array of enzymatic properties
      that nature has evolved, as well as the strategies that nature has used to evolve
      them, are becoming an increasingly important avenue for obtaining novel enzymes
      with desired activities and properties.

PMID- 9652139
TI  - Perfluorochemicals: their applications and benefits to cell culture.
AB  - The properties of perfluorochemical liquids, particularly their high gas
      solubility, enables them to be exploited in cell biotechnology. They can
      facilitate respiratory-gas delivery to prokaryotic and eukaryotic cells in
      culture; in some systems, they can stimulate production of biomass, yields of
      commercially important cellular products and, for plant systems, expression of
      totipotency. The recoverability, and hence recycleability, of perfluorochemicals
      from aqueous systems makes their routine use a commercially feasible option. This
      article reviews the applications and beneficial effects of perfluorochemicals in
      cultured microbial, animal and plant cells, including both aerobic and anaerobic
      systems.

PMID- 9652138
TI  - Using molecular techniques to identify new microbial biocatalysts.
AB  - Evolution has favoured microorganisms that produce efficient enzymes with
      substrate-adapted biocatalytic activities. Progress in molecular techniques,
      especially expression cloning, molecular screening, protein engineering and in
      vivo and in vitro shuffling, have paved the way for greater speed and accuracy in
      cloning enzyme genes from microorganisms and generating versions with improved
      properties. Recently, two new approaches have been added: screening directly from
      uncultivated microorganisms and generating additional hits by database mining
      using bioinformatic tools.

PMID- 9652140
TI  - A sparsely vascularised zone in the cortex of the bovine ovary.
AB  - We consider that the microvascular bed may play a role in the initiation and
      maintenance of growth from primordial to primary follicles. Therefore, using
      immunochemistry, we examined microvessels in calf and cow ovaries to identify the
      presence of factor VIII-related antigen endothelial cells. A vessel-poor zone was
      observed in the cortex of immature and mature cow ovaries. Primordial and primary
      follicles were assembled in this zone. It is concluded that follicular dormancy
      is likely to be maintained by the scarcity of microvessels and thus by the
      consequent poverty of the blood supply.

PMID- 9652142
TI  - Occurrence and importance of glomus organs (Hoyer-Grosser's organs) in the skin
      of the equine and bovine mammary gland.
AB  - Glomus organs (Hoyer-Grosser's organs) were frequently found in the corium and
      the subcutis of the skin of the equine and bovine mammary gland. They were most
      frequently situated in the border zone between the stratum profundum and the
      stratum superficiale corii. These specialized vascular structures (arterio-venous
      anastomosis) were present in all investigated skin areas. Although the glomus
      organs varied in size and shape, they possessed common histologic structures: an
      arteriole entered the connective capsule of the glomus and divided into strongly
      convoluted arterio-venous channels; the arteriovenous channels united in the end
      to form a venule; the mentioned vascular elements were covered by a connective
      capsule and were thus united to an organ-like structure. Questions concerning
      their occurrence, their functional interpretation, their relevance, the size of
      the glomus organs as well as the possible involvement of the lymphatics were
      discussed.

PMID- 9652141
TI  - Histochemistry of complex carbohydrate in the major salivary glands of hoary
      bamboo rats (Rhizomys purinosus).
AB  - The major salivary glands (parotid glands, monostomatic sublingual glands and
      submandibular glands) were obtained from hoary bamboo rats (Rhizomys purinosus)
      and fixed in Bouin's solution. Paraffin sections were subjected to a battery of
      staining methods including lectin staining for demonstration of complex
      carbohydrates. Among the three major salivary glands, unique histochemical
      features were observed in the submandibular gland. Different from most myomorpha
      species, submandibular glands of the hoary bamboo rats have two types of
      secretory cells in the secretory endpieces. One type of cells showed positive
      reactions with Alcian blue (AB)(pH2.5), periodic acid-Schiff (PAS) and some
      lectins (peanuts agglutinin, Griffonia simplicifolia I, Maclura pomifera
      agglutinin). The granular ducts, which exist in animals belonging to suborder
      myomorpha, were not observed in the submandibular glands of this animal.

PMID- 9652143
TI  - Chemoreceptive epithelioid cells in the chicken aorta. An electron microscopical
      study.
AB  - Aggregations of granulated epithelioid cells exist in the chicken aorta. In the
      present study, the locational characteristics of the epithelioid cells were
      investigated via an electron microscopic approach. Epithelioid cells were found
      mainly in two regions; the tunica interna just below the endothelial cell layers,
      and the intermediate region of the tunica media. In the former, the epithelioid
      cells were in contact with endothelial cells and sometimes directly exposed to
      the aortic lumen. No contact between the epithelioid cells and the nerve endings
      was observed in this region. On the other hand, in the intermediate region of the
      tunica media, five or more epithelioid cells were aggregated, and the synaptic
      structures were occasionally observed. Additionally, the epithelioid cells in
      this region was observed to closely contact smooth muscle cells. In an experiment
      using horseradish peroxidase injection, reactions were detected in the
      intercellular spaces between the epithelioid cells and endothelial cells. These
      results suggest that the epithelioid cells localized in the subendothelial region
      receive information from the aortic lumen, whereas their aggregations in the
      tunica media are controlled by the nervous system.

PMID- 9652144
TI  - [Anatomic characteristics pf the elbow joint of the cheetah (Acinonyx jubatus)].
AB  - Anatomical structures of elbow joints of six cheetahs were examined by
      dissection, corrosion casts and radiography. As a result, it was observed that
      the distal end of humerus is divided into the trochlea humeri for articulation
      with the ulna and the capitulum humeri for articulation with the radius. As the
      trochlea humeri is posed oblique and looks like a disc-shaped cone sector,
      flexion. Flexion of elbow joint is always combined with adduction of the distal
      parts of the limb, and, respectively, extension with abduction. The cylindrical
      but also in sagittal direction convex capitulum humeri enables the head of the
      radius all movements on a spheric sector. Furthermore, advantageous preconditions
      for rotation in the proximal radioulnar joint are the mighty medical coronoid
      process, the displacement of the radial tuberosity to the caudal surface of the
      radius and the insertion of the biceps brachii muscle exclusively on this
      elevation of the radius. Limiting factors are the insertions of collateral
      ligaments at the antebrachial skeleton. The lateral collateral ligament inserts
      only on the radius, the medial collateral ligament mainly on the ulna. The radial
      anular ligament directly connects the two coronoid processes of the ulna and
      moreover is intracapsular. The joint capsule is common for both the cubital and
      the proximal radioulnar joint and five pouches could be described. These were
      between the lateral epicondyle of humerus and the olecranon, underneath the
      tendon of origin of the extensor carpi ulnaris muscle, cranially in the bend of
      the elbow joint, between the head of the radius and the tendon of origin of
      supinator muscle and the lateral part of radial anular ligament, just as between
      the medial epicondyle of humerus and the tendons of origin of flexor muscles of
      the forearm.

PMID- 9652145
TI  - Morphological and immunohistochemical considerations on the basal ganglia in
      pigeon (Columba livia).
AB  - Morphological and immunohistochemical studies carried out particularly around the
      level of the basal ganglia (BG) in birds, are reported and commented on. Our
      results showed, on paraffin embedded avian BG, both the histological features and
      the immunohistochemical findings on immunofluorescence distribution of some
      neuropeptides (especially Metenkephalin) in the striatal complex. By comparing
      our results of Metenkephalin immunoreactivity (Menkir) with the referred
      analogous ones of Substance P (SP) quoted in literature, we confirmed the
      strikingly similar labelling at the levels of the Lobus paraolfactorius (LPO) and
      Paleostriatum augmentatum (PA), in contrast with the very low immunoreactivity at
      the Paleostriatum primitivum (PP) levels. We were able also to demonstrate the
      strong MEnk-ir of the neurons of the Nucleus accumbens, Nucleus septalis and
      paraventricularis. All these findings are also in accord to the interpretation by
      many AA (Wynne and Gunturkun, 1995; Reinez et al., 1983), about the anatomical
      correspondence between the LPO-PA complex of birds and the caudate-putamen in
      mammals. Some MEnk + 'wooly like fibres' described in our specimens in the PA (on
      the contrary reported in the Gpe segment of mammals) apparently escape these
      correspondence.

PMID- 9652146
TI  - An immunohistochemical study of bovine palatine and pharyngeal tonsils at 21, 60
      and 300 days of age.
AB  - An immunohistochemical study was performed on three groups of young cattle (21,
      60 and 300 days of age). Tonsils (palatine and pharyngeal) and mucosae (nasal and
      oral) were removed. Eight monoclonal antibodies (specific for CD3, CD2, CD4, CD8,
      WC1, cell-surface IgM, cell-surface IgG and MHC class II molecules) and an
      avidin/biotin complex method on frozen sections were used. The immunological
      cytoarchitecture of bovine tonsils is similar to that of human tonsils.
      Nevertheless, these lymphoid tissues are not fully developed during the first
      weeks of life: T and B dependent areas not well-differentiated, few germinal
      centres, few intra-epithelial WC1+ T lymphocytes. In contrast, at 2 months,
      tonsils possess all the elements of a mucosa-associated lymphoid tissue (MALT).
      Tonsillar or mucosal epithelium is infiltrated by a large number of CD8+, WC1+ T
      lymphocytes and cells which express MHC class II molecules. Between 21 and 60
      days, the number of WC1+ T lymphocytes increase markedly in the tonsillar
      epithelium. These results accredit the hypothesis that the presence of antigens
      has an effect on the localization of these lymphocytes at these sites.

PMID- 9652148
TI  - Studies on the parietal region of the cervid skull. III. On the occurrence of an
      interparietal in Cervus.
AB  - The occurrence of an os interparietal was studied in two transparent preparations
      of fetal red deer (Cervus elaphus) heads and in 14 dried skulls of fetal to early
      postnatal individuals from four Cervus species (C. elaphus, C. nippon, C.
      duvauceli and C. eldi). In 14 of the 16 specimens, an interparietal was present
      as either a paired or single bone. In only a neonate red deer and a 5-week-old
      sika deer this skull element was missing. We therefore conclude that an os
      interparietal, developing from paired centres of ossification, is normally
      present in Cervus species. This clearly distinguishes them from the fallow deer,
      where an interparietal is missing (Kierdorf and Kierdorf, 1992b). Our findings
      thus support the view that the fallow deer should be considered a distinct genus
      Dama instead of being included within Cervus.

PMID- 9652147
TI  - Immunohistochemical study of normal and mange (S. scabiei var. rupicaprae)
      infested chamois (Rupicapra rupicapra L.) skin.
AB  - The immunohistochemical study of chamois (Rupicapra rupicapra L.) skin showed
      that a limited number of available monoclonal and polyclonal antibodies expressed
      reactivity with skin cell components. These included cytokeratins, vimentin,
      desmin, neuron-specific enolase and S-100 protein with almost the same
      distribution pattern as already described in the skin of humans and animals.
      Antibodies used for labelling skin-associated lymphoid tissues and other cells
      with the immunologic function in human skin failed to demonstrate these cells in
      the chamois skin with the exception of LCA and OKT6 antibodies. Epidermal
      Langerhans cells were reliably demonstrated only by the enzyme histochemical
      method for adenosine triphosphatase, while the majority of mononuclear cells in
      dermal infiltrates showed a strong immunoreaction with OKT6 antibody. The
      histologic and histochemical analysis showed that the dermal infiltrations in
      infested skin consisted of macrophages, lymphocytes, granulocytes, mastocytes and
      fibroblasts. The chamois skin affected with sarcoptes mange showed a significant
      loss of cytokeratins in the epidermis and its derivatives. Particular
      keratinocytes showing nonspecific staining with several antibodies were also
      described and discussed in this paper.

PMID- 9652149
TI  - Distention of the lateral intercellular spaces (LIS) in the proximal tubule cells
      of the non-stenosed kidney of the 2K-1C Goldblatt model of hypertension as
      evidence of pressure diuresis.
AB  - This study shows the development of two major deformities in the non-stenosed
      kidney of the 2K-1C Goldblatt model; namely the widening of the LIS and the
      enlargement of the basilar interdigitations of the proximal tubule cells. These
      deformities were much less in the 2K-1C animals treated with the angiotensin I
      converting enzyme inhibitor (AICEI) cilazapril. From these findings it is
      suggested that the non-stenosed kidney is operating under the diuretic effect of
      the elevated systemic blood pressure (SBP) via an increase in the renal
      interstitial hydrostatic pressure (RIHP). Therefore, the AII antidiuretic effect
      is masked by the diuretic effect of the elevated SBP. The suggested rise in urine
      output fits well with the idea that kidneys lose water and sodium when SBP
      increases enormously. Therefore, in this model of hypertension, the non-stenosed
      kidney tries to lower SBP by losing water and sodium, an excretion behavior which
      is opposite to that of the stenosed kidney. Thus, the rise in SBP in this model
      is probably due to an increase in the vascular peripheral resistance rather than
      fluid accumulation.

PMID- 9652150
TI  - Regional peripheral vascular supply based on the superficial temporal artery in
      dogs and cats.
AB  - Cutaneous arterial blood supply to the temporal region was evaluated in 8 dogs
      and 8 cats. Subtraction radiography and angiography of the carotid and
      superficial temporal arteries were used in 4 dogs and 4 cats to determine
      arterial blood supply to the temporal region and frontalis muscle. A myocutaneous
      axial pattern flap based on the superficial temporal artery and frontalis muscle
      may be indicated for cosmetic reconstruction in dogs and cats following surgical
      resection of neoplastic lesions or traumatic wounds in the maxillofacial region.
      The frontalis muscle was identified as the thin subcutaneous continuation of the
      platysma muscle extending cranially and rostrally. Dissection of the temporal
      region in 4 dogs and 4 cats revealed the subcutaneous location of the superficial
      temporal artery as it continues rostrally from the caudal aspect of the zygomatic
      arch.

PMID- 9652151
TI  - Immunohistochemical demonstration of cytoskeletal proteins in the testis of the
      Japanese black bear, Ursus thibetanus japonicus.
AB  - The seasonal changes of the cytoskeletal protein expressions were
      immunohistochemically investigated in the testes of Japanese black bear, Ursus
      thibetanus japonicus. A strong immunoreaction for alpha-smooth muscle actin is
      restricted to the vascular smooth muscle cells and the peritubular cells which
      surround the seminiferous tubules by several layers throughout the year. Weak
      immunoreactions for B4 antigen and desmin were observed in the vascular smooth
      muscle cells and in a part of peritubular cells throughout the year. A strong
      immunoreaction for vimentin was also detected in the fibroblasts and Leydig
      cells, in addition to the vascular smooth muscle and epithelial cells and the
      peritubular cells throughout the year. A strong alpha-tubulin immunoreaction was
      detected in the elongating spermatids during the acrosome phase of spermiogenesis
      in May and June. The cytoplasm of several Sertoli cells was faintly immunoreacted
      for vimentin in the basal and lateral region, while an intense alpha-tubulin
      reaction was seen in the entire cytoplasm in May, April and June. In November,
      January and March, the immunoreactions for vimentin and alpha-tubulin strongly
      accumulate in a perinuclear region of Sertoli cells when developmental spermatids
      are not seen in the seminiferous tubules. These accumulations in the
      immunoreactions for vimentin and alpha-tubulin seem to be caused by the reduction
      in size of Sertoli cells cytoplasm with season. However, the seasonal changes of
      distributions in the cytoskeletal proteins are obscure in the bear testes. These
      results suggest that the contents of cytoskeletal proteins may not change in
      relation to the morphological differences with season in the testes of the
      seasonal breeders.

PMID- 9652152
TI  - Births, marriages, divorces, and deaths for November 1997.

PMID- 9652153
TI  - Biocompatible dialysis membranes: do they matter?

PMID- 9652154
TI  - Overview of dialyzer elution studies: impact on current views on
      bioincompatibility and future perspectives.

PMID- 9652155
TI  - Haemodialysis-related bioincompatibility: fundamental aspects and clinical
      relevance.

PMID- 9652156
TI  - The newly developed sulfonylurea glimepiride: a new ingredient, an old recipe.
AB  - Disturbances in insulin secretion and insulin action are both involved in the
      pathophysiology of type 2 (or non-insulin-dependent) diabetes mellitus. The newly
      developed sulfonylurea (SU) derivative glimepiride has a marked insulin secretory
      effect both in vitro and in vivo, and is capable of increasing plasma insulin
      levels with approximately 50% in type 2 diabetes subjects. Glimepiride improves
      metabolic control comparable but not superior to other (second generation) SU
      derivatives. Although it has been advocated for once-daily use, maximum effect is
      presumably achieved by twice-daily dosing. One of the most important side-effects
      of SU remains hypoglycemia in some patients, which may last for several hours.
      Although there is some indication that the use of glimepiride leads to fewer
      hypoglycemic episodes than glibenclamide, the differences reported sofar are not
      statistically significant.

PMID- 9652157
TI  - Jaundice associated with acenocoumarol exposure.
AB  - A 69-year-old man developed cholestatic liver enzyme disturbances three and a
      half weeks after starting treatment with acenocoumarol because of a deep venous
      thrombosis in his leg. Serological testing showed no signs of recent viral
      infections. A presumptive diagnosis of hepatotoxicity caused by the use of
      acenocoumarol was made and the anticoagulant was replaced by low molecular weight
      heparin. Three weeks after withdrawal of the acenocoumarol, the enzymes had
      improved. The patient made a full recovery within two months. This case suggests
      a causal relationship between acenocoumarol exposure and liver damage.

PMID- 9652158
TI  - A patient with acquired haemophilia A and pemphigus.
AB  - Haemophilia A is usually a genetic deficiency of coagulation factor VIII (F
      VIII). The development of antibodies against F VIII is a well known and frequent
      complication in the treatment of haemophilia A. Rarely, a F VIII inhibitor arises
      spontaneously, causing a condition which is known as acquired haemophilia A. We
      describe a patient with acquired haemophilia A and pemphigus, who presented with
      spontaneous haematomas of the extremities. Laboratory tests showed an activated
      partial thromboplastin time (aPTT) of 71 s (normal: 26-36 s), a F VIII
      concentration of 9% (normal: 60-140%), and a F VIII inhibitor-activity of 7.5
      Bethesda Units/ml (B.U./ml, normal: 0). The haematomas disappeared within a few
      days and the laboratory tests normalized within 6 weeks, after administration of
      a booster of oral corticosteroids. One and a half years after the corticosteroids
      were stopped, both the clinical and the laboratory course of the patient has been
      uneventful. As far as we know, the combination of acquired haemophilia A and
      pemphigus has been reported in the literature only three times before. The
      diagnosis acquired haemophilia A should be considered in a patient presenting
      with a newly arisen haemorrhagic diathesis.

PMID- 9652159
TI  - Primary oligoarthritis in a parent of a child with meningococcal group B sepsis
      and meningitis.
AB  - The mother of an eight-month-old child with meningitis presented with petechiae
      on her trunk and lower extremities, fever, and oligoarthritis. Although pathogens
      were never revealed by Gram stain nor cultured from the aspirated joint fluid,
      the diagnosis was primary meningococcal arthritis. This diagnosis was based on
      the simultaneous occurrence of Neisseria meningitidis group B infection in her
      son and the clinical presentation.

PMID- 9652160
TI  - [The P-pill debate. From media circus to critical risk evaluation].

PMID- 9652161
TI  - [P-pills and thrombosis].
AB  - This review provides an account of the present situation as reflected by findings
      in recent studies, which illustrate epidemiological, clinical and metabolic
      aspects of thrombosis associated with oral contraceptive (OC) usage. With the
      reduction of the oestrogen content of OCs, the relative risk for acute myocardial
      or cerebral thrombosis is now 1.5-3. Low-dose OCs containing third generation
      gestagens seem to be associated with less risk of infarction, and possibly of
      cerebral thrombosis, than are OCs containing second generation gestagens. The
      risk of venous thrombosis is increased 2-4-fold in conjunction with the usage of
      low-dose OCs with second generation gestagens, and possibly slightly more (3-5
      fold) in conjunction with OCs containing third generation gestagens, though this
      is of small clinical significance. When prescribing OCs for women at an increased
      risk of venous thrombosis, a low-dose pill with a second generation progestagen
      seems to be preferable. If OCs are prescribed to women at an increased risk of
      arterial thrombosis, OCs with third generation progestagens seem to be a
      reasonable first choice.  Women with no thrombotic predisposion can safely use
      any type of low-dose OCs [corrected].

PMID- 9652162
TI  - [For some it is a matter of necessity. Worry about the overuse of an
      antidepressant].

PMID- 9652163
TI  - [How soon will we have artificial blood?].
AB  - The development of red cell substitute oxygen-carriers has reached a stage where
      stroma-free haemoglobin solutions (SFHSs) and perfluorocarbon-based substitutes
      are undergoing clinical trials. However, there is no evidence to suggest that
      such products will become available, other than for restricted, well-defined
      indications. Where SFHSs are concerned, the supply of haemoglobin, the strictly
      limited shelf-life, and the short intravascular half-life are the most important
      problems to be solved, whereas the use of perfluorocarbons is limited, in
      particular due to the need of positive pressure ventilation to maintain high
      oxygen tension. Red cell substitutes for general use will remain a dream in the
      foreseeable future. Measures to enhance blood preservation and to promote the
      optimal use of blood products will be the most important areas of transfusion
      research in the immediate future.

PMID- 9652164
TI  - [Malrotation--a rare cause of recurrent abdominal pain in children].

PMID- 9652165
TI  - [Patient readmission. Medical diagnosis and risk factors of emergency readmission
      within 14 days].
AB  - Every tenth patient discharged from a medical department at a general hospital in
      Sweden during the period, 1992-1994, required emergency re-admission within 14
      days. The risk of re-admission appeared to be unrelated to the duration of
      hospitalisation before discharge or to the occupancy rate. However, a high risk
      of emergency re-admission was found to be associated with four diagnoses: acute
      myocardial infarction, angina pectoris, heart failure and chronic obstructive
      lung disease. Plans are under way to launch a multicentre intervention study of
      emergency re-admission to departments of medicine.

PMID- 9652166
TI  - [Causes of death and incidence of cancer in physicians and lawyers in Iceland].
AB  - A retrospective study is accomplished in Iceland to study whether mortality and
      cancer incidence among male physicians (1,210) were lower than those among men of
      the general population and lawyers (1,032). Overall mortality among lawyers was
      similar to that of the general male population, however, mortality among the
      physicians was lower than that of the general population and the lawyers, due to
      lower mortality for all cancers (SMR 0.73), cerebrovascular diseases (SMR 0.53)
      and respiratory diseases (SMR 0.54). The physicians had higher mortality for
      suicide committed by drugs, solid or liquid substances. Cancer was not as
      frequent among the physicians as among the lawyers, particularly for lung cancer,
      the SIR was 0.45, but the rates were higher for cancer of the colon and brain
      among the physicians than among others.

PMID- 9652167
TI  - [The merit profile--an instrument for the evaluation of academic achievement].
AB  - The concept of a merit profile has been evolved at Karolinska Institute in
      Stockholm, whereby not only research achievements but also teaching,
      administrative and clinical skills and experience are each given merit ratings to
      produce an individual profile. This approach is based on the notion that all of
      these fields of activity constitute integregal facets of a scat of higher
      learning in medicine, and that a candidate's relative merits in each of these
      areas should be seen not only in relation to the overall academic goals but also
      to practical, professional considerations. The merit profile is intended to be
      used in selection for appointments and promotion, and as a basis for the
      continued enhancement of individual competence, and salary review.

PMID- 9652169
TI  - Long-term vs. short-term journal impact: does it matter?

PMID- 9652168
TI  - Citation statistics for the individual journals of The American Journal of
      Physiology.

PMID- 9652170
TI  - Structure and function of molybdopterin containing enzymes.
AB  - Molybdopterin containing enzymes are present in a wide range of living systems
      and have been known for several decades. However, only in the past two years have
      the first crystal structures been reported for this type of enzyme. This has
      represented a major breakthrough in this field. The enzymes share common
      structural features, but reveal different polypeptide folding topologies. In this
      review we give an account of the related spectroscopic information and the
      crystallographic results, with emphasis on structure-function studies.

PMID- 9652171
TI  - Self-organization in biology and development.

PMID- 9652172
TI  - The intrinsic viscosity of biological macromolecules. Progress in measurement,
      interpretation and application to structure in dilute solution.

PMID- 9652173
TI  - Chloride channels in the sarcoplasmic reticulum of muscle.

PMID- 9652174
TI  - AIDS and education: have we done enough?

PMID- 9652175
TI  - Liver transplantation in chronic hepatitis B--a new era?

PMID- 9652176
TI  - Liver transplant in Singapore--coming of age.
AB  - BACKGROUND/AIM OF STUDY: Liver transplantation was first performed in 1967, and
      has become an accepted form of treatment worldwide for chronic liver diseases,
      acute liver failure and certain metabolic diseases. We document our experience in
      Singapore over the last 7 years since the first transplant was performed in 1990.
      METHOD: Retrospective study at National University Hospital, Singapore. RESULTS:
      Twenty-two operations (10 paediatric and 12 adults) have been performed with the
      last 17 having been performed in the last 17 months. Currently, there are 15
      survivors (68%) since 1990, and percentage survival is even better if one
      considers the cases from the last 17 months when the majority of cases (17
      transplants-77%) were performed (77% survival). The most common indication for
      transplant was biliary atresia for the paediatric group, while the adults were
      transplanted for hepatitis B and C cirrhosis, primary biliary cirrhosis, and
      fulminant liver failure. Tacrolimus is the main immunosuppression (10 patients),
      with the remaining 5 patients on cyclosporine. Various surgical techniques
      (living donor, graft reduction) have been employed successfully to provide a
      complete transplant service. Hospital and ICU stays are within normal limits and
      the hospital charges range from a low of S$30,000 to S$141,000. CONCLUSION: Liver
      transplantation has become a reality in Singapore with outcomes comparable to
      other transplant centres. The shortage of donors remains the greatest stumbling
      block for further expansion.

PMID- 9652177
TI  - A needs assessment and proposal for HIV education among human resource managers
      in Singapore.
AB  - AIM OF STUDY: To assess the educational needs of human resource managers in
      Singapore with regard to the management of HIV at the workplace. No such study
      has been described before in an Asian country. METHOD: A self-administered
      questionnaire was mailed to all companies (with more than 100 employees) of a
      local employers federation (n = 368). RESULTS: A response rate of 64.1% was
      achieved. Respondents' knowledge about HIV transmission was found to be good.
      However, their attitudes and practices towards infected workers were unfavourable
      on such issues as pre-employment screening, medical coverage and termination of
      employment. Possible reasons for this disparity include inadequate information
      specific to workplace needs, multiple determinants of attitudes (other than
      knowledge) and various environmental factors. CONCLUSION: Strategies for an
      educational intervention are proposed to facilitate the development of a rational
      HIV management policy by local managers.

PMID- 9652178
TI  - Distribution patterns of inflammatory sinonasal diseases.
AB  - BACKGROUND/AIM OF STUDY: There has been an increase in the demand for coronal
      sinus CT scan since the introduction of functional endoscopic sinus surgery; as
      the information provided by the scans assist the surgeon in the pre-operative
      plannings. Babbel and colleagues had demonstrated five distinctive patterns of
      recurring inflammatory sinonasal disease on CT scan. The aim of this study was to
      evaluate the patterns in the local population and to see if there was a
      difference compared to the Caucasian population. METHODS AND MATERIALS: A
      retrospective review of 302 scans done between March 1993 and September 1995 was
      carried out. All scans were carried out using a 5 mm thickness to cover the
      posterior sinuses and a 3 mm thickness to cover the anterior sinuses. The scans
      were then grouped into the various patterns and an analysis was carried out
      comparing the differences in the patterns between the Chinese and the non
      Chinese, and between the local population and the Caucasian population in
      Babbel's series. RESULTS: There was no significant difference between the Chinese
      and the non-Chinese in the distribution of the various disease patterns. When
      compared to the Caucasian population, the local population had more sinonasal
      polyposis and sphenoethmoidal recess obstruction. CONCLUSION: The smaller nasal
      passages of the Asians, particularly in the Chinese, could be the reason for the
      more prevalence of Type III and Type IV disease compared to the Caucasian
      population. The more constant and frequent exposure to allergens might also
      contribute to the increased prevalence of Type IV disease.

PMID- 9652179
TI  - Transcatheter closure of patent ductus arteriosus using detachable spring coils.
AB  - OBJECTIVE: To report our experience with transcatheter PDA closure using
      detachable spring coils. METHODS: Suitable patients who presented between March
      1996 to July 1997 were selected for coil occlusion of PDA after the diagnosis is
      confirmed on colour doppler echocardiography. Twenty-seven patients underwent an
      attempt at transcatheter closure of PDA with coils. Twenty-one were native ducts
      while 6 were residual ductal leaks following surgical ligation (4) and Rashkind
      umbrella occlusion (2). RESULTS: The patients' age ranged from 20 months to 39
      years (median 5.5 years) and weighed from 10.5 kg to 49 kg (median 21 kg). The
      PDA diameter ranged from 1.3 mm to 5 mm (mean 2.4 mm). Twenty-four patients had
      coils successfully deployed (one coil in each patient) and all had PDA diameter
      of < or = 3.5 mm. Seventeen had complete occlusion on echocardiographic colour
      doppler assessment within 24 hrs. Follow-up colour doppler assessment showed
      complete occlusion in all 24 patients by 6 months. There were no cases of coil
      embolisation or any other complications. Unsuccessful coil deployment was
      encountered in 3 patients with PDA diameter of > or = 4 mm. CONCLUSION: The
      detachable coil system allows for complete control over coil release and
      therefore deployment is precise and complications are minimised. Transcatheter
      closure of PDA with the detachable coil is a safe and effective method especially
      for small ducts (< or = 3.5 mm).

PMID- 9652180
TI  - Down syndrome screening in Singapore--the effectiveness of a second trimester
      serum screening policy modelled on 29,360 pregnancies in KK Women's and
      Children's Hospital.
AB  - AIM OF STUDY: To assess the effectiveness of a proposed second trimester Down
      syndrome serum screening policy in Singapore. METHOD: Auditing the effectiveness
      of an age-only policy and comparing it against a serum screening policy modelled
      on the same maternal population of KK Women's and Children's Hospital in 1994 and
      1995. RESULTS: KK Women's and Children's Hospital's (KKH) maternal age
      distribution is similar to the national age distribution of mothers. Sixteen
      percent (16.7%) of mothers in KKH, in 1994 and 1995, were 35 years or older at
      delivery. Based on our hospital birth defect registry, 66% (35/53) of Down
      Syndrome pregnancies occurred in mothers who were 35 years or older at delivery
      and 43% (23/53) in the oldest 6.5% of mothers (38 years or older at delivery).
      Using various models on KKH's population structure to estimate the expected
      number of Down Syndrome livebirths expected, 52%-55% and 34%-36% of Down Syndrome
      livebirths were expected to occur in the oldest 16.7% and 6.5% of mothers
      respectively. These simulated figures are much lower than the figures from the
      data and needs further study, assuming that the Western Down Syndrome risk model
      to be applicable to our population. The overall uptake of amniocentesis
      irrespective of gestational age at booking was 28%. In mothers who were 35 years
      or older at delivery and booked before 22 weeks gestation, the uptake rate of
      amniocentesis was 49%. There was a substantial difference in the uptake rate when
      the counselling was done by trained counsellers compared to those who were not.
      CONCLUSION: We would expect that for a fixed amniocentesis rate of 6.5% and
      16.7%, serum screening would be able to detect 71% and 85% respectively of the
      Down syndrome pregnancies. This is more efficient than figures published from
      Western populations as our patients are older.

PMID- 9652181
TI  - L-asparaginase induced intracranial haemorrhage in acute lymphoblastic leukemia.
AB  - A 20-year-old national serviceman with acute lymphoblastic leukaemia, developed a
      large left parieto-occipital haemorrhage 7 days after completion of induction
      chemotherapy. Severe hypofibrinogenemia had been noted while he was receiving L
      asparaginase. The haemorrhage could not be attributed to thrombocytopenia,
      disseminated intravascular coagulopathy, arterio-venous malformation, berry
      aneurysm or leukaemic infiltration because each of these causes was carefully
      investigated into and excluded. We conclude that the intracranial haemorrhage was
      likely L-asparaginase induced, an uncommon but recognised complication associated
      with L-asparaginase therapy.

PMID- 9652182
TI  - Surgical reconstruction for mesenteric angina in a patient with infra-renal
      aortic occlusive disease--a case report and review.
AB  - Mesenteric angina is an uncommon condition which is underdiagnosed, or diagnosed
      too late when the patient has a mesenteric infarct. The preferred treatment is by
      surgical reconstruction. A case presented here illustrates the condition and the
      modifications necessary to reconstruct a completely occluded lower abdominal
      aorta in treating both mesenteric angina and claudication.

PMID- 9652183
TI  - A review of the role of stroke units in the modern day management of stroke-
      implications for stroke care in Singapore.
AB  - Among the strategies to combat stroke, an important cause of mortality and
      morbidity in Singapore, is the establishment of stroke units. Stroke units are
      characterised by a geographical co-location of stroke patients or care by a
      mobile multidisciplinary stroke team of specialists; the provision of 24-hour CT
      scanning, laboratory, monitoring, neurology and neuroradiology services, and
      availability of neurosurgical and angiography services is recommended. Stroke
      intensive care units are expensive to run and do not reduce mortality-however,
      they may have a role for the aggressive management of carefully selected
      patients. Non-intensive stroke and rehabilitation units have been shown to reduce
      mortality, morbidity, institutionalisation, and even length of stay and
      healthcare costs. They facilitate better utilisation of resources, audit,
      teaching and clinical research. As the number of stroke patients in Singapore is
      expected to rise, with minor reorganisation, all Singapore hospitals should be
      able to establish their own stroke units.

PMID- 9652184
TI  - Acute hepatitis in an asthmatic patient.

PMID- 9652185
TI  - Diagnostic difficulties associated with phaeochromocytoma.

PMID- 9652186
TI  - Asthma therapy for the 21st century.

PMID- 9652187
TI  - On the presence of a putative fourth beta-adrenoceptor in human adipose tissue.

PMID- 9652188
TI  - An orange a day keeps the scurvy away.

PMID- 9652189
TI  - Fibroblast models of neurological disorders: fluorescence measurement studies.
AB  - Biochemical studies of human fibroblasts from patients with neurological
      disorders have revealed a wealth of information on how such disorders occur. In
      this review, Gerald Connolly describes how recently developed fluorescence video
      imaging techniques have been used to study the physiology of skin fibroblasts
      isolated from patients with certain neurological disorders, including those
      produced by Alzheimer's disease, Lesch-Nyhan syndrome, mitochondrial disorders,
      amyotrophic lateral sclerosis and lysosomal disorders. The results of these
      studies indicate disruptions in cell homeostasis, particularly specific changes
      in Ca2+ homeostasis and autofluorescence, which mirror changes thought to occur
      in the CNS of neurologically impaired patients. More extensive studies of these
      'systemic changes' using new fluorescent indicators, combined with advances in
      imaging techniques, are predicted to increase the potential usefulness of human
      skin fibroblasts as experimental models and to help diagnose and treat
      neurological disorders.

PMID- 9652190
TI  - Therapeutic potential of histamine H3 receptor agonists and antagonists.
AB  - The histamine H3 receptor was discovered 15 years ago, and many potent and
      selective H3 receptor agonists and antagonists have since been developed.
      Currently, much attention is being focused on the therapeutic potential of H3
      receptor ligands. In this review, Rob Leurs, Patrizio Blandina, Clark Tedford and
      Henk Timmerman describe the available H3 receptor agonists and antagonists and
      their effects in a variety of pharmacological models in vitro and in vivo. The
      possible therapeutic applications of the various compounds are discussed.

PMID- 9652192
TI  - Your life in your hands. A surgeon's view of hand function--art expression and
      form.

PMID- 9652191
TI  - Adenosine A3 receptors: novel ligands and paradoxical effects.
AB  - The physiological role of the adenosine A3 receptor is being investigated using
      newly synthesized, selective ligands. Recently, in addition to agonists,
      selective antagonists have been developed that belong to three distinct, non
      purine chemical classes: flavonoids, 1,4-dihydropyridine derivatives (e.g.
      MRS1191, which is 1300-fold selective for human adenosine A3 vs A1/A2A receptors,
      with a Ki value of 31 nM) and the triazoloquinazolines (e.g. MRS1220, which has a
      Ki value of 0.65 nM). The A3 receptor has proven enigmatic in terms of antagonist
      ligand specificity, coupling to second messengers, and biological effects in the
      CNS, inflammatory system and cardiovascular system. A3 receptors are also
      potentially involved in apoptosis. It appears that intense, acute activation of
      A3 receptors acts as a lethal input to cells, while low concentrations of A3
      receptor agonists protect against apoptosis. Here, Kenneth Jacobson describes how
      A3 receptor agonists might be useful in treating inflammatory conditions,
      possibly through their inhibition of tumour necrosis factor alpha (TNF-alpha)
      release, which has been shown in macrophages. A3 receptor antagonists might be
      useful in treating asthma or acute brain ischaemia. Recently, the versatility of
      A3 receptor agonists, administered either before or during ischaemia, in
      eliciting potent cardioprotection has been shown.

PMID- 9652193
TI  - Drug overdoses requiring temporary cardiac pacing; a study of six cases treated
      at Altnagelvin Hospital, Londonderry.
AB  - Drug overdoses in general are increasing and overdoses of cardiac medications are
      also increasing; some are associated with a high mortality. Temporary cardiac
      pacing has a valuable role in cases of hypotension related to dysrhythmia, or
      when it is necessary to provide overdrive pacing. However, despite technically
      successful and uncomplicated pacemaker insertion and restoration of cardiac
      electrical activity, patients developing bradyarrhythmia and hypotension after an
      overdose are in a high risk group.

PMID- 9652194
TI  - A review of direct current cardioversions for atrial arrhythmia.
AB  - The risk of arterial embolism is well recognised following Direct Current
      Cardioversion (DCC) for atrial fibrillation although the use of prophylactic
      anticoagulation remains controversial. AIM: To determine the risk of arterial
      embolism post-cardioversion and which factors predict successful cardioversion
      and maintenance of sinus rhythm. MATERIALS AND METHODS: A retrospective study was
      carried out of all cardioversions performed for atrial fibrillation and atrial
      flutter at the Waveney Hospital Ballymena, during 1989-1993. A review of medical
      records and electrocardiograms was carried out to assess demographic
      characteristics, co-existent diseases, anticoagulant status, echocardiographic
      features and characteristics of the arrhythmia. Embolic events in the six weeks
      post-cardioversion were noted. RESULTS: The study included 157 cardioversions in
      109 patients. The predominant arrhythmia was atrial fibrillation (n = 108, 69%).
      Three of 109 patients (2.7%) experienced embolic complications, none of whom had
      anticoagulation prior to the procedure. No risk factors for cerebro-vascular
      disease or significant valvular heart disease were present. Return to sinus
      rhythm was achieved in 143 (91%) procedures. Increasing coarseness of atrial
      fibrillation was associated with a non-significant trend towards successful
      restoration of sinus rhythm (p = 0.18). Recurrence of the original arrhythmia was
      predicted by an increase in coarseness of atrial fibrillation (p < 0.05).
      CONCLUSIONS: These findings indicate that embolic complications can occur in
      patients undergoing DCC with normal echocardiographic dimensions, and that
      prophylactic anticoagulation should be considered in all patients. Coarseness of
      atrial fibrillation may be used as a guide to predict the chance of successful
      cardioversion and of the likelihood of maintaining sinus rhythm once this has
      been achieved.

PMID- 9652195
TI  - The haematuria clinic--referral patterns in Northern Ireland.
AB  - One hundred consecutive patients with haematuria were seen over a three month
      period at the haematuria clinic, Belfast City Hospital. 14% of patients were
      found to have transitional cell carcinoma of the urinary bladder; all of these
      presented with frank haematuria and were over 50 years of age. No malignancy was
      detected in the microscopic haematuria group. 14% of patients with macroscopic
      haematuria held back for longer than one month before seeking advice from their
      general practitioner. 23% with macroscopic and 30% with microscopic haematuria
      had their symptoms noted by the general practitioner for more than a month before
      they were referred for investigation. The waiting time for initial investigation
      at the haematuria clinic took longer than six weeks in 52% with macroscopic and
      39% with microscopic haematuria. Our study has identified a high-risk group who
      need immediate referral and investigation. The importance of patient education,
      rapid referral by general practitioners and also the need to increase the
      capacity of the haematuria clinic are emphasized.

PMID- 9652196
TI  - Trans-cervical resection of the endometrium: the first four years' experience at
      the Belfast City Hospital.
AB  - We have evaluated the quality of service provided in performing trans cervical
      resection of the endometrium (TCRE) in the treatment of women presenting with
      menstrual dysfunction. Of the 78 patients who underwent TCRE, ten had, at the
      time of writing, subsequently undergone hysterectomy. A chart review was carried
      out on those patients. Two others were on the waiting list for hysterectomy.
      Sixty-one of 68 (90%) patients responded to the postal questionnaires. Of these,
      50 (82%) were satisfied with the result of the procedure. Twenty-three (38%) were
      rendered amenorrhoeic. Thirty-eight still had bleeding, but of these, 19 (31%)
      had very light regular periods and 13 (21%) had only an occasional stain.
      Overall, 90% of women felt that there had been an improvement in their bleeding.
      Six (10%) women claimed that there had been no improvement. TCRE is a safe and
      effective alternative to hysterectomy or medical treatment for the treatment of
      menstrual dysfunction.

PMID- 9652197
TI  - The effects of depression awareness seminars on general practitioners knowledge
      of depressive illness.
AB  - The Royal Colleges of Psychiatry and General Practice wish to increase knowledge
      of depressive illness among patients and professionals. This study reports the
      results of a series of depression education seminars in a Health Board in
      Northern Ireland. Seminars lasted 2 1/2 hours and included didactic teaching and
      interactive case management vignettes. 88 general practitioners took part (39% of
      those eligible). Seminars increased knowledge as measured by questionnaire
      immediately, but this did not appear to be sustained at one year, when compared
      to a group of general practitioners with no access to such seminars. Educational
      programmes as described do not appear to have a sustained effect on general
      practitioners' knowledge of depressive illness.

PMID- 9652198
TI  - A prospective study of the process of assessment and care management in the
      discharge of elderly patients from hospital.
AB  - Assessment and care management (ACM) of elderly patients prior to discharge from
      hospital has been in place since 1993. It involves a complex multi-disciplinary
      assessment of needs which may delay discharge from hospital. We prospectively
      studied the process of ACM in a group of patients discharged from hospital over a
      three month period. The times taken for completion of the necessary reports, and
      any delays in the process were recorded. The times of each individual step in the
      process were correlated to overall length of stay and to the length of the care
      management process. The effect of intercurrent illnesses or other delays was
      studied. Of the available sample (n = 83), 16 patients died and two required long
      term hospital care. The median length of stay of the remainder (n = 65) was 36
      days (range 5-149 days). The median time from the start of the ACM process to
      discharge was 22 days (0-89 days). The strongest correlation with total length of
      stay was the time from admission until ACM commenced (rho = 0.661, p < 0.0001).
      The time spent in the ACM process was related strongly to the time taken for the
      Care Manager to process the applications (rho = 0.682, p < 0.0001). Delay was
      recorded in 17 (24%) cases, resulting in an increased length of stay (p < 0.001).
      While care management may help in appropriate placement after hospital discharge,
      these results suggest that it is prone to delays outside the hospital setting.
      Such delays result in patients waiting in hospital for care packages to be set up
      in the community. This has implications for acute hospital services.

PMID- 9652199
TI  - Audit of the management of spontaneous pneumothorax.
AB  - This audit suggests that clinical practice in the management of spontaneous
      pneumothorax differs from guidelines issued by the British Thoracic Society. In
      particular simple aspiration was attempted in only seven out of 65 patients and
      clamping of an intercostal chest drain occurred in 12 out of 50 cases. Junior
      medical staff require more training in intercostal drainage.

PMID- 9652200
TI  - An audit of acute psychiatric admission bed occupancy in Northern Ireland.
AB  - The Northern Ireland Section (Irish Division) of the Royal College of
      Psychiatrists were requested to investigate apparent increasing pressures on
      acute psychiatric beds. Information on bed occupancy and associated service
      activity was collected by clinicians on site in every psychiatric unit in
      Northern Ireland over the past eight years. Three separate years (1987, 1991 and
      1995) were studied. Bed occupancy rose across these three years. There was an
      associated reduction in the number of acute psychiatric beds, reduction in adult
      continuing care beds, increased recorded referrals to psychiatric units and
      evidence of considerable numbers of new long-stay patients and difficulties with
      community placements. Acute bed occupancy in Northern Ireland is high, frequently
      over 100% and rising. Occupancy rose between each of the years studied. The
      problem is not confined to urban areas and several associated service factors may
      be contributing. Without change, acute bed provision will inevitably fail to
      match mental health needs.

PMID- 9652201
TI  - Anaesthesia and the broken hearted. 170th annual oration: Royal Victoria
      Hospital, Belfast 2nd October 1997.

PMID- 9652202
TI  - The successful use of spinal cord stimulation to alleviate intractable angina
      pectoris.

PMID- 9652203
TI  - Primary breast lymphoma.

PMID- 9652204
TI  - Hypoparathyroidism--presenting 40 years after thyroid surgery.

PMID- 9652205
TI  - Leprosy elimination campaigns (LECs). Progress during 1997-1998.

PMID- 9652206
TI  - Dengue and dengue haemorrhagic fever, Malaysia.

PMID- 9652207
TI  - Smallpox eradication--a cold war victory.

PMID- 9652208
TI  - Organ transplantation in developing countries.
AB  - Organ transplantation has become an effective means of restoring health and
      saving lives, but a number of difficulties remain to be overcome. Especially in
      developing countries, greater clarity is needed on the sociocultural, economic,
      ethical, legal and technical factors involved.

PMID- 9652209
TI  - Culture and psychology in organ transplantation.
AB  - The cultural and psychological dimensions of organ transplantation are often
      overlooked in the process of meeting its exacting technical requirements. This
      new branch of medicine has brought with it new ways of understanding death, human
      rights, commerce, gift giving, and ethics. It produces strong emotions in
      recipients, donors and transplanters alike. These factors need to be taken fully
      into consideration if organ transplantation is to evolve in ways that are felt to
      be beneficial for all concerned.

PMID- 9652210
TI  - A halfway house for pregnant women.

PMID- 9652211
TI  - Saving mothers' lives: things can go wrong.
AB  - One of the goals of Sierra Leone's primary care programme, established in the
      1980s, was to reduce maternal mortality by 30% by the end of the twentieth
      century, but no significant progress has been made in this direction. The reasons
      are examined below in the light of a study conducted in one of the country's
      Chiefdoms.

PMID- 9652212
TI  - WHO at fifty. Highlights of activities from 1961 to 1973.
AB  - In this second article to mark the fiftieth anniversary of the World Health
      Organization in 1998, World Health Forum briefly reviews the work of the
      Organization, highlighting some of the wide range of activities carried out or
      promoted by WHO from 1961 to 1973. This period covers the remaining years of Dr
      M.G. Candau's tenure as Director-General and the appointment of Dr Halfdan T.
      Mahler who succeeded him on 21 July 1973.

PMID- 9652213
TI  - District hospitals in Turkey.

PMID- 9652214
TI  - Effect of referral on deaths from cholera.

PMID- 9652215
TI  - Research to prevent injuries.

PMID- 9652216
TI  - Structural adjustment and health.

PMID- 9652217
TI  - Protecting the world's children: the story of WHO's immunization programme.
AB  - Systematic immunization on a worldwide scale was not officially recognized as a
      practical possibility until 1974, when WHO launched its Expanded Programme on
      Immunization. Today, 80% of the world's children receive this form of protection
      against childhood diseases during their first year of life. Coverage can reach
      90% by the year 2000, the effectiveness of the vaccines used is improving, and
      vaccines against additional diseases are being added to the programme.

PMID- 9652218
TI  - From disease control to child health and development.
AB  - The control of diarrhoeal diseases, acute respiratory infections and other
      childhood killers--such as measles, malaria and malnutrition--is now combined in
      WHO's Division of Child Health and Development. The need for integrated
      management of childhood illness is shown in its historical context.

PMID- 9652219
TI  - The poorest first: WHO's activities to help the people in greatest need.
AB  - Through its Division of Intensified Cooperation with Countries and Peoples in
      Greatest Need, WHO is giving special attention to the relationship between
      poverty and ill-health. The work of the Division is outlined in the present
      article.

PMID- 9652220
TI  - All hands against polio.
AB  - The students and faculty of the Aga Khan University School of Nursing, working in
      collaboration with other groups and organizations, have made a considerable
      contribution to Pakistan's polio immunization programme in the area of District
      Council West and Malir, Karachi. Recommendations for improving the programme are
      presented on the basis of the experience gained.

PMID- 9652222
TI  - Free high-tech health care in India.
AB  - The Sri Sathya Sai Institute of Higher Medical Sciences in Andhra Pradesh can
      claim to have achieved the impossible--namely, the provision of high-tech medical
      services completely free of charge. Adherence to the five human values (truth,
      righteousness, peace, love and non-violence) and complete dedication to serve
      people without self-interest are the key elements for this success. This example
      may serve as a model for creating similar hospitals in the service of mankind.

PMID- 9652221
TI  - Onchocerciasis control in Uganda.
AB  - In 1990 a community-based programme of onchocerciasis control, involving the use
      of ivermectin, was introduced in Uganda. The problems confronting it are
      discussed and suggestions are made for making it sustainable.

PMID- 9652223
TI  - Forms of better care.
AB  - The introduction of forms called critical care pathways into the paediatric unit
      of a hospital in Malawi has strengthened teamwork and helped to increase the
      efficiency with which resources are employed. They serve the dual function of
      indicating good management and providing an opportunity to note actions and
      potential progress.

PMID- 9652224
TI  - Emergency health training programme for Africa.

PMID- 9652225
TI  - Progress in leprosy elimination.

PMID- 9652226
TI  - Counterfeit pharmaceutical products.

PMID- 9652227
TI  - AIDS in Africa.

PMID- 9652228
TI  - Anti-personnel mines.

PMID- 9652229
TI  - Chromosomal structure and recombination between inversions in Drosophila
      subobscura.
AB  - Drosophila subobscura is a species with rich chromosomal polymorphism. More than
      45 arrangements have been described in the O chromosome. The recombination
      between them is an interesting topic, because many nonoverlapping arrangements
      are inherited together. In the analysis of recombination between the arrangements
      O7 and O3 + 4 + 8, out of 415 individuals observed none was found to be
      recombinant. The same result was obtained in the study of the recombination
      between the inversions O5 and O3 + 4, in which 437 individuals were analyzed. In
      this case a significant non equivalent segregation was found, the O5 chromosomes
      being more frequent than expected. This phenomenon could be explained by three
      hypotheses: a meiotic drive, a greater fitness of the individuals carrying this
      inversion and heterotic effect of a wild chromosome in combination with a
      chromosome from an inbred laboratory strain. If the second hypothesis is correct,
      it could explain why an inversion always associated with a lethal gene in
      American populations is not infrequent and presents a clinal distribution in the
      colonized areas. Furthermore, another inversion, O22, is very similar to O5.
      These two inversions can be distinguished only by careful observation. Although
      O22 and O5 are very similar they show different behavior in the wild, probably
      due to the combinations of genes included in them.

PMID- 9652230
TI  - Sexual selection related to developmental stability in Drosophila buzzatii.
AB  - Relationships among developmental stability, sexual selection, and body size were
      examined in the cactophilic fly Drosophila buzzatii. Developmental stability, as
      measured in terms of fluctuating asymmetry (FA) of wing length, was positively
      associated to male's copulatory success in a mass-mating experiment with wild
      reared flies. Previous studies showed that body size is positively correlated
      with mating success and other fitness components in this species, but no
      phenotypic correlation between wing asymmetry and size was found in the present
      study. Thus, wing asymmetry does not indicate male quality in terms of phenotypic
      variation in body size. This study suggests that sexual selection against wing
      asymmetry may be mediated through unknown factors related to developmental
      stability rather than body size.

PMID- 9652231
TI  - Characterization of cCel3, a member of the pepper endo-beta-1,4-glucanase
      multigene family.
AB  - In pepper plants the enzyme endo-beta-1,4-glucanase (EGase) is encoded by a
      multigene family. Here is described the characterization of cCel3, a cDNA which
      codes for the third EGase known so far in this plant. The known members of this
      family are present as single copy genes, as demonstrated by a Southern analysis
      of the genomic DNA. Analysis of the expression of cCel3 demonstrates that the
      highest levels of the cCel3 mRNA are found in abscission zones of leaves and
      flowers activated by treatments with the plant hormone ethylene. However, the
      amounts of the cCel3 transcripts (detectable only by RT-PCR) are always much
      lower than those of cCel2 so that the latter can be regarded as the "abscission"
      EGase while cCel3 is likely to perform a role ancillary to that of cCel2.

PMID- 9652232
TI  - Cytoplasmic diversity in leaf beet cultivars as revealed by mitochondrial DNA
      analysis.
AB  - Mitochondrial (mt) DNA restriction fragment length polymorphisms are convenient
      markers for identifying cytoplasmic variation among plant cultivars. In an
      attempt to detect new cytoplasmic genotypes useful for sugarbeet breeding, we
      have compared the hybridization patterns of mtDNA from three groups of cultivated
      beets, viz. leaf beet, garden beet, and fodder beet. Utilized as probes were the
      two sugarbeet mtDNA clones that were capable of distinguishing normal fertile and
      different sources of male-sterile cytoplasms from one another. The analysis
      allowed the identification of four chondriome types among 14 leaf beet cultivars
      examined. Two out of the four chondriome types were found to be different from
      the previously described fertile or male-sterile chondriome type. Our results
      thus indicate that leaf beet cultivars and landraces make up the primary
      cytoplasmic gene pool of the sugarbeet.

PMID- 9652233
TI  - Mitochondrial control region polymorphism reveal high amount of gene flow in
      Fennoscandian willow tits (Parus montanus borealis).
AB  - We studied the genetic variability and differentiation of two Fennoscandian
      willow tit (Parus montanus borealis) populations located ca. 1000 km apart in
      Finland and Sweden by using the control region sequences of the mitochondrial
      DNA. Individual variation in the control region was extensive since all the 13
      Finnish and the 12 Swedish individuals had unique haplotypes and the mean
      pairwise genetic distance resulted in 0.0052 (range 0.0008-0.0109). In the
      minimum spanning network connecting the genotypes, the two populations were
      completely intermingled. The mismatch distribution of the combined data set was
      very close to expected distribution of an expanding population. This result was
      supported by a significantly negative Tajima's D value. The sequence data
      indicate that (1) the long-term effective population size of the breeding willow
      tits has been large (122,000 and 110,000 females for the Finnish and the Swedish
      populations, respectively); and that (2) the gene exchange between distant
      localities is/has been extensive. Dispersal area for the Finnish females was
      estimated to be about 19,000-30,000 km2 and for the Swedish, 22,000-28,000 km2.
      Thus, the whole Fennoscandian population can be regarded as one panmictic unit,
      without any subdivisions to local demes. The amount of gene flow is remarkable
      because the willow tit has been considered a highly sedentary species. Provided
      that adult birds are site-tenacious, the gene flow must occur through juvenile
      summer dispersal, or irruptive autumn invasions, or both.

PMID- 9652234
TI  - Detection of individual variation in enzyme activity in natural populations of
      Drosophila melanogaster.
AB  - The method allows the determination of the activity level of enzymes in a single
      fly and assessing the genetic composition of the given individual at these enzyme
      loci. Three isofemale lines were constructed which were monomorphic at several
      enzyme loci. Samples were prepared in two different ways: (i) individual samples-
      individuals were homogenised separately; (ii) collective samples--a common
      homogenate was prepared from several individuals. Oregon-R strain was also used
      to prepare a standard homogenate. The activities of alcohol dehydrogenase (ADH),
      alpha-glycerophosphate dehydrogenase (alpha GPDH), isocitrate dehydrogenase
      (IDH), and 6-phosphogluconate dehydrogenase (6PGDH), were measured in each sample
      on starch gel after the proteins were separated by electrophoresis. Enzyme
      activities were assessed by the optical density of the bands. Gel and position
      weights were estimated on the basis of the statistical analyses of the activities
      measured in the standard samples. Gel weights were then used to account for the
      activity differences among the gels while position weights were applied to
      correct for the general tendencies in the activities observed within the gels.
      The gel and position weighted activities of individual and collective samples
      were compared in the isofemale lines. The individual samples had approximately
      two times as much variation as the collective samples for all four enzymes. The
      electrophoretic method is sensitive enough to study the structure of the
      phenotypic variation in enzyme activity in the natural populations. The total
      variation among the standard samples was close to the within subline component of
      variation obtained for the collective samples (measurement error). This shows
      that the standard samples can be used to estimate the size of the measurement
      error.

PMID- 9652235
TI  - Mutants and duplication in chromosome 7 (syn. 5H) in the barley line HA21:
      duplications may enhance QTLs and serve to make constant linear cis
      heterozygosity.
AB  - Cytological and linkage data indicate a duplication in the short arm of
      chromosome 7 (syn. 5H) in the mutant line HA21 (barley, Hordeum vulgare, cv.
      'Pirkka'). The associated mutant (ha21) shows a weighted average linkage of 22.1
      cM with pld, hitherto an ignored anthocyaninless gene, of cv. Pirkka. Some
      crosses produce F2 segregants with an exaggerated ha21 phenotype which may
      represent position effect or increased dosage of the mutant gene through
      recombination. Compared with cv. Pirkka, HA21 has changes in grain chemistry
      (alpha- and beta-amylase, beta-glucanase), which may be caused by changed QTL
      dosage or QTL position effect due to duplication. The use of duplication in
      creating constant +m/+ m or m+/m+ linear cis-heterozygotes is suggested. Linear
      cis-heterozygotes may produce stable heterosis or attenuate the undesired effects
      of drastic mutants.

PMID- 9652236
TI  - Treatment of hand and wrist pain. A randomized clinical trial of high voltage
      pulsed, direct current built into a wrist splint.
AB  - To determine the effectiveness of high voltage pulsed current (HVPC) in reducing
      chronic hand edema, 120 individuals were randomly assigned to one of two
      treatment groups. Group I clients were given an appropriate sized wrist splint,
      incorporating an energized, high voltage pulsed unit. Group II clients were given
      an identical splint with a non-energized unit. Each client received daily
      treatments at the worksite consisting of 30 minute sessions totaling 20
      treatments during a 35 day period. Pre-treatment and post-treatment evaluations
      included measurements of pain, grip strength, and edema volume; repetitive task
      testing; and Semmes-Weinstein Monofilament sensory testing. In the energized
      group, post-treatment evaluation showed statistically significant decreases in
      the amount of stimulation required to stimulate the median nerve and the amount
      of hand edema and pain. The energized group also had improved repetitive task
      times. None of these improvements occurred in the non-energized group. Based on
      these results, HVPC appears to be an effective method for minimizing the severity
      of repetitive stress injuries of the wrist.

PMID- 9652237
TI  - Effectiveness of a worksite smoking cessation program in the military. Program
      evaluation.
AB  - 1. A program evaluation was conducted to evaluate the effectiveness of the
      smoking cessation program. Substantiating data enhances the value of health
      promotion programs as key components of the health care delivery system. 2.
      Persons enrolled in the 8 week smoking cessation program and members of a
      comparison group were administered an evaluation tool prior to participating in
      the program, with a second evaluation tool upon completion of the program.
      Afterward, the smoking status of the members of both groups was evaluated at 3
      month intervals for a period of 1 year. 3. Of the participants, 26.7% were not
      smoking 12 months after the program, compared to 6.9% of the comparison group. Of
      those participants who resumed smoking, 64% smoked less than half the amount they
      smoked before taking the class.

PMID- 9652238
TI  - Occupational exposure of health care workers to bloodborne pathogens. A proposal
      for a systematic intervention approach.
AB  - 1. Each year approximately 6,500 to 9,000 health care workers in the United
      States are exposed to infectious body fluids while on the job. The majority of
      the resultant clinical infections causing morbidity and mortality are
      attributable to bloodborne pathogens. 2. The relatively simple approach of
      educating workers so they comply with exposure control systems has continued to
      be employed by many infection control and employee health specialists, despite
      the temporary and/or negligible effects demonstrated from high risk health care
      employees. 3. The reduction of worksite transmission of bloodborne pathogens
      through the increased use of system wide and worksite engineering techniques has
      been advocated by experts, demanding increased consideration from health care
      planners and researchers.

PMID- 9652239
TI  - Non-steroidal antiinflammatory drugs. A review.
AB  - 1. Non-steroidal antiinflammatory drugs (NSAIDs) are among the most frequently
      prescribed medications and are used primarily to control pain, stiffness, and
      reduce inflammation. 2. One of the most common adverse effects of NSAID therapy
      is gastrointestinal (GI) problems, specifically indigestion, nausea, dyspepsia,
      diarrhea, constipation, and gastritis. 3. Considerations in chronic pain
      management include non-pharmacologic treatment options (i.e., physical therapy,
      behavioral therapy, etc.), use of misoprostol for clients at high risk for NSAID
      induced GI problems, and monitoring blood and urine every 3 months to 1 year with
      chronic NSAID therapy to detect liver, kidney, and hematologic problems. 4.
      Current research is focused on development of a prostaglandin H synthetase (PGHS
      2) inhibitor which should offer efficacy equal to the most potent NSAIDs with
      minimal side effects, including gastric safety.

PMID- 9652241
TI  - Descriptive analysis of research data.

PMID- 9652240
TI  - Avoiding the millenium bug.

PMID- 9652242
TI  - Project management, Part III. Budgets for projects.

PMID- 9652243
TI  - The truth ... the whole truth.

PMID- 9652244
TI  - Rehabilitation of an adolescent with medulloblastoma.

PMID- 9652245
TI  - A multidimensional measure of fatigue for use with cancer patients.
AB  - PURPOSE: The purpose of this study was to develop and validate a multidimensional
      measure of fatigue for use with cancer patients. DESCRIPTION OF STUDY: Items for
      the Multidimensional Fatigue Symptom Inventory (MFSI) were generated through
      literature review, discussion with healthcare providers, and a survey of
      currently available measures of fatigue. The 83-item MFSI was designed to assess
      global, somatic, affective, cognitive, and behavioral symptoms of fatigue. The
      instrument was administered on three occasions to 275 women who had received or
      were undergoing treatment for breast cancer and 70 women with no history of
      cancer. Reliability, validity, and factorial structure of the MFSI were analyzed.
      RESULTS: The factor analysis produced five empirically derived scales that
      correspond generally to the five rationally derived scales. Reliability of the
      rationally and empirically derived scales was excellent (alpha coefficients .87
      to .96). Estimates of test-retest reliability were also favorable. Other results
      support the validity of both the rationally and empirically derived scales. The
      MFSI appears to be sensitive to fatigue, accurately discriminating cancer
      patients from control subjects and between patients with varying levels of
      performance status. CLINICAL IMPLICATIONS: The MFSI may be useful in identifying
      patterns of fatigue within individual patients and across treatment modalities.
      Such specificity may allow the clinician to develop, implement, and evaluate
      interventions that are targeted for differing patterns of fatigue. Because the
      measure is keyed to a 1-week time frame, it may be useful during the course of
      cancer treatment. The MFSI appears to be a valid and reliable tool to assess the
      full spectrum of symptoms that characterize the construct of fatigue.

PMID- 9652246
TI  - Cross-cultural issues in the disclosure of cancer.
AB  - PURPOSE: To increase awareness of cultural differences in the disclosure of a
      cancer diagnosis or prognosis, the author reviews several surveys of patients and
      physicians from around the world. OVERVIEW: The Western medical community is
      increasingly emphasizing full truthful disclosure of cancer diagnoses or
      prognoses and respect for autonomy as necessary prerequisites to ethical
      practice. However, surveys of European, Japanese, Native American, and various
      ethnic American (including Korean, Chinese, Mexican, Hispanic, African, and
      European American) cancer patients and physicians reveal that many cultures
      consider complete and accurate disclosure of cancer undesirable. Cultural
      differences in the rates of disclosure of a cancer diagnosis or prognosis; the
      physician's use of euphemisms to give a true or false diagnosis; as well as
      considerations of how to disclose a cancer diagnosis are described. CLINICAL
      IMPLICATIONS: Developing an awareness about cross-cultural practices regarding
      cancer disclosure issues allows the clinician to become more sensitive to the
      expectations of culturally and individually diverse cancer patients. To this end,
      all healthcare professionals should be informed about how the patient would like
      to be informed of a diagnosis and how involved he or she would like family
      members to be. In addition, an awareness of the use of nonverbal communication in
      some cultures and the psychosocial impact of certain terms, such as "cancer," is
      essential. Often, phrases such as "malignant tumor" or "growth" are less
      inflammatory and are more readily accepted. In ascertaining a knowledge of
      various cultural preferences and developing a sensitivity to these preferences,
      clinicians are better able to provide effective care to individuals from a
      variety of cultural and individual backgrounds.

PMID- 9652247
TI  - Selecting and implementing support groups for bereaved adults.
AB  - PURPOSE: This paper offers a rationale for initiating bereavement support groups
      in sites providing cancer care and delineates models to implement them. Skills
      needed to lead a bereavement support group are identified, with emphasis on
      adding to staff members' competency that has already been developed by
      facilitating groups for oncology patients and their families. OVERVIEW:
      Bereavement support groups are essential elements in the provision of
      comprehensive oncology care, though they are seldom offered by staff in the
      traditional hospital setting. It is important that the bereaved feel that there
      is a place in which they have the time and understanding required to work through
      the normal grieving process. Special requirements for facilitators include self
      awareness of the impact of loss in their own lives and ability to tolerate both
      the emotions expressed in the grieving process and the often extended time period
      required for members' personal healing. Several bereavement support models,
      including the time-limited, ongoing, monthly, and self-help groups, are
      documented. CLINICAL IMPLICATIONS: Bereavement support is an essential element in
      the provision of comprehensive oncology care. Predictive models to identify
      individuals who are at higher risk for psychological distress could be used in
      oncology clinics to facilitate early referral or greater psychological support
      for family members. Staff members wishing to introduce this service can build on
      skills already developed leading traditional oncology support groups, and can
      utilize cofacilitation with a mental health professional to ease the anxiety of
      assuming a new role and obtain mentoring. Recruitment for a group might be
      achieved by inviting family members of patients who have died within a specific
      time frame or by issuing press releases to local papers and church bulletins.
      Offering bereavement support in the oncology setting is especially helpful to
      family members who might otherwise be unaware of such a service and who now have
      the opportunity to attend.

PMID- 9652248
TI  - Colorectal cancer screening. Knowledge and practices among Korean Americans.
AB  - PURPOSE: The purpose of this study was to examine knowledge and practices of
      colorectal cancer screening among Korean Americans. DESCRIPTION OF STUDY: The
      sample consisted of 104 Korean American men and 159 women, 40 to 69 years of age,
      living in the Chicago area. The National Health Interview Survey (NHIS) Cancer
      Control Supplement Questionnaire, prepared by the National Center for Health
      Statistics, was used to collect data regarding colorectal cancer screening
      knowledge and practices. The NHIS questionnaire was translated into Korean with
      minor modification. RESULTS: The percentage of male respondents ever having had a
      digital rectal exam (DRE) and fecal occult blood test (FOBT) were 13.5% and
      10.6%, respectively. Only 11.3% of women reported DRE and 8.8% FOBT. Multiple
      logistic regression analysis results indicate that gender, education, knowledge
      of the seven cancer warning signals, and length of residence in the United States
      were significantly related to having heard of DRE. For those having had DRE,
      knowledge of the seven cancer warning signals, and length of residence in the
      United States were the only significant variables. Gender and education were
      significantly related to having heard of FOBT. None of the variables were found
      to be significantly related to having had FOBT. The findings indicate that a
      majority of respondents were unaware of these cancer screening examinations and
      forego these tests due to an underestimation of their importance. CLINICAL
      IMPLICATIONS: The findings of this study underscore the importance of cancer
      education and further research addressing the cancer screening needs of Korean
      Americans. Currently, Korean Americans do not see healthcare providers or health
      brochures as valuable sources of health information. Therefore, healthcare
      professionals need to target this population by 1) coordinating their efforts
      with church and other community leaders and 2) developing health brochures that
      are in the Korean language and sensitive to the Korean culture.

PMID- 9652249
TI  - Alternative care. Patient choices for adjunct therapies within a cancer center.
AB  - PURPOSE: Prompted by an increased interest in and awareness of alternative
      medicine, the Sutter Cancer Center in Sacramento, California, sponsored a
      telephone survey of its cancer patients. The primary purpose of this 1994 survey
      was: 1) to determine patient perceptions and attitudes regarding alternative care
      providers, and 2) to determine whether the Sutter Cancer Center should provide
      support for these types of therapies to its patients. DESCRIPTION OF STUDY: The
      Center conducted a 95-item telephone survey of its patients with cancer, using an
      independent professional research firm. A random sample of 503 adult patients
      completed the 15-minute telephone survey between January 27 and March 8, 1994.
      The sample included more women than men (62%, 38%, respectively), and patients
      ranged in age from 18 to 88 years. All respondents had been treated for cancer at
      the Center within the past 2 years. Survey questions included areas such as
      cancer diagnosis, awareness of alternative therapies, attitude toward alternative
      therapies, and perception of oncologists' attitude toward alternative therapies.
      The analysis of the survey results contained two phases: descriptive analysis and
      comparative analysis. The descriptive aspect is included in this report. RESULTS:
      Of the 503 respondents, 82 (16%) had considered utilizing alternative therapy for
      cancer after a diagnosis was made. Most respondents were moderately familiar with
      alternative therapy, such as nutrition therapy (59%), herbal therapy (63%), and
      acupuncture (62%). Only 6% of respondents actually saw a provider of alternative
      therapies; providers were most frequently nutritionists, counselors, herbalists,
      and massage therapists. The user patient profile clearly indicates that usage is
      highest in patients with a diagnosis of at least 1 year. Seventy-five percent
      reported that they would prefer to receive a referral from their doctors, while
      20% would prefer to use a telephone referral line. Two thirds of patients felt
      that alternative care providers should be encouraged by the medical profession,
      and 85% indicated that alternative care should be offered at the cancer center as
      part of oncology treatment. CLINICAL IMPLICATIONS: The results of this survey
      clearly reflect the patients' desires to integrate mainstream medicine with some
      forms of alternative/complementary medicine. Consequently, the Sutter Cancer
      Center has established a multidisciplinary group of healthcare professionals,
      including oncologists, nurses, social workers, and alternative practitioners, to
      evaluate the clinical, psychosocial, and financial impact of integrating
      wellness/complementary medicine into the existing treatment model at this
      facility. Providing alternative therapy within a cancer center ensures the
      availability of both the most advanced conventional treatment and care as well as
      accurate information and guidance with regard to alternative therapies. This
      service allows the patient and the cancer care team to focus not only on the
      patient's physical symptoms, but also on his or her overall quality of life.

PMID- 9652251
TI  - End-of-life care: hospice or home?

PMID- 9652250
TI  - Cost considerations as potential barriers to cancer treatment.
AB  - PURPOSE: An analytical cross-sectional survey was conducted to determine the
      prevalence of barriers to cancer treatment in Texas as perceived by diagnosed
      cancer patients. Results reported here address the role of insurance coverage,
      indirect costs (transportation, lodging, and work days lost), and direct costs of
      care as barriers to treatment for white, black, and Hispanic cancer patients.
      Specific objectives of the analyses undertaken here are to examine 1)
      racial/ethnic differences in insurance coverage; 2) barriers relating to
      insurance coverage experienced by cancer patients; and 3) role of treatment
      related costs as barriers to cancer treatment. DESCRIPTION OF STUDY: A mail
      questionnaire was developed to assess the perceived barriers to cancer treatment
      in Texas for adult cancer patients, 17 years and older, who had been diagnosed
      with breast, colon, cervical, prostate, or lymphoma during the period of 1989 to
      1993. The sampling frame for this study was obtained from a network of cancer
      treatment facilities throughout the state of Texas within the University of Texas
      M.D. Anderson Cancer Center Texas Community Oncology Network. A total of 593
      cancer patients returned their surveys, yielding a 65.2% response rate. Weighting
      adjustments were then made to correct for differential sampling and response
      rates by racial groupings and type of cancer. All of the analyses used adjusted
      weights. RESULTS: The findings document the financial considerations (insurance,
      direct and indirect costs) as they relate to barriers to cancer treatment.
      Specific insurance premium-related barriers with regard to maintaining and
      affording coverage were more prevalent for blacks. Hispanics were less likely to
      have insurance coverage; however, more blacks reported being denied insurance
      coverage when they changed jobs compared with whites and Hispanics. Minorities,
      particularly Hispanics, were more likely to have experienced cost-related
      barriers associated with medications, diagnostic tests, and hospitalizations. In
      addition, Hispanics experienced significant out-of-pocket costs in paying for
      cancer treatment. CLINICAL IMPLICATIONS: This research shows the need for staff
      at cancer treatment facilities to be aware that there are nonclinical, financial
      factors that are important considerations in the treatment of cancer patients.
      Assessment of cancer patients during the diagnostic and treatment stages,
      possibly through case management, will provide information on potential barriers
      to treatment for individual patients. Hospital programs that reimburse out-of
      pocket costs, transportation costs to obtain services, and lodging accommodations
      may be available. Additional services may be offered through cancer advocacy
      groups, such as the American Cancer Society and the National Coalition for Cancer
      Survivors, to assist patients with managing costs and overcoming barriers to
      care.

PMID- 9652252
TI  - Culturally relevant "Navigator" patient support. The Native sisters.

PMID- 9652253
TI  - Rituximab: a new therapeutic monoclonal antibody for non-Hodgkin's lymphoma.
AB  - Rituximab is an effective single agent available for short-course outpatient
      treatment in low-grade NHL, particularly with follicular histology (IWF B-D),
      that offers a relatively nontoxic alternative to chemotherapy regimens currently
      available. Early indications are that retreatment is effective with similar
      levels of predictable adverse events to the initial course of therapy. Further
      development is awaited of regimens that combine rituximab with chemotherapeutic
      agents to enhance treatment efficacy without overlapping side effects in low
      grade NHL as well as use in other CD20+ malignancies.

PMID- 9652254
TI  - The debate of the age: the ageing population.

PMID- 9652255
TI  - Parental presence during resuscitation: attitudes of staff on a paediatric
      intensive care unit.
AB  - Although family presence during resuscitation is becoming more acceptable, many
      medical and nursing staff still have concerns and doubts about it. To ascertain
      paediatric medical and nursing staff's attitudes towards parents being present
      during resuscitation, 60 staff in a Paediatric Intensive Care Unit were surveyed.
      The results revealed that even though 89% of staff feel that parents should be
      able to be present, many have the same concerns and doubts that have been
      highlighted in previous, albeit adult-centred, studies. Increased stress to staff
      and parents were some of the concerns identified in a study which also showed
      interest in the subject and a need for further education.

PMID- 9652256
TI  - Parental anxiety due to abnormal behaviour following withdrawal of sedation.
AB  - Abnormal behaviour has been previously reported on withdrawal of sedation in
      critically-ill children. This description of a child who had prolonged withdrawal
      symptoms lasting almost 2 weeks includes a report on his parent's comments in
      relation to the anxiety they felt while he was behaving abnormally. Health
      professionals need to be aware of the severe nature of this withdrawal reaction
      and its effect on the parents.

PMID- 9652257
TI  - Role extension or expansion: a qualitative investigation of the perceptions of
      senior medical and nursing staff in an adult intensive care unit.
AB  - The Scope of Professional Practice (UKCC 1992) has significantly altered the
      interpretation of nurses' roles, emphasizing individual professional
      accountability and clinical decision-making. However, 5 years after the issue of
      the document, uncertainties remain regarding interprofessional legal
      accountability between medicine and nursing. To investigate issues surrounding
      role extension or expansion in intensive care nursing, a small qualitative study
      was conducted centred on one intensive care unit (ICU) within a large teaching
      hospital. Data were collected by semi-structured interviews from a purposive
      sample of five senior intensive care nurses and three consultant anaesthetists.
      Four major categories emerged, identified as: interpretation confusion; education
      for change; struggles for power and task versus autonomy. The findings revealed
      that the senior critical care nurses identified themselves as independent,
      autonomous practitioners involved in clinical decision-making. However, there was
      evidence of a reluctance to empower more junior staff to perform extended or
      expanded roles. Medical respondents viewed extended or expanded roles as taking
      on mechanical tasks for which anyone could be trained to perform. In conclusion,
      it is argued that although nursing is maturing in its growth towards
      professionalization, broader issues such as the legal quagmire, failure to adopt
      the philosophy of role expansion and the existence of sacred boundaries intra-
      and inter-professionally need to be addressed.

PMID- 9652259
TI  - Establishing evidence-based practice: issues and implications in critical care
      nursing.
AB  - Evidence-based practice is the application of the best available empirical
      evidence, including recent research findings to clinical practice in order to aid
      clinical decision-making. The implementation of these findings is vital for
      optimizing patient outcomes, improving clinical practice, providing cost
      effective high quality care and enhancing the credibility of nurses. The use of
      research findings to improve practice has been discussed and promoted for the
      last 20 years. The author argues that Rogers' theoretical model of the Diffusion
      of Innovations may prove useful in understanding the problem of the slow
      diffusion of the application of research evidence in clinical nursing practice.
      Many authors have discussed potential barriers to using research in clinical
      practice in order to facilitate utilization of findings. However, recent studies
      all document that a gap between research findings and their implementation in
      clinical practice still exists. This appears to hold true across a variety of
      practice settings, including nurses working in critical care. The diffusion of
      innovations in current critical care nursing practice at each stage of Rogers'
      theory will be examined, with recommendations given to facilitate the
      establishment of evidence-based practice (EBP).

PMID- 9652258
TI  - Brain death in ICUs and associated nursing care challenges concerning patients
      and families.
AB  - In order to document the incidence and causes of brain death (BD) and the
      frequency of organ donation (OD) in a Swedish University Hospital, a
      retrospective review of deaths in a neurosurgical department and in the general
      intensive care units (ICUs), was carried out for the period 1988-1994. BD
      diagnosis was established in 197 (10.6%) of all deaths (n = 1843). The hospital
      records of all BD patients were examined in detail following a specific study
      plan. The majority of the BD patients (89%) were acute admissions to hospital,
      and among them 81 were transferred between hospitals often over a long distance.
      Among the BD patients the total number of OD was 65 (33%). The most common
      diagnosis leading to BD was spontaneous intracerebral bleeding and traumatic head
      injury. The BD diagnosis was established by neurological examination (60%) and by
      cerebral angiography (40%). Of the BD patients, 50% died within 48 hours in the
      ICU and the majority of requests for OD (67%) were made to the relatives of these
      patients. The findings are discussed with focus on the workload and psychological
      stress of ICU nurses when caring for BD patients and their families; a task which
      includes taking part in processes concerning BD diagnosis information and OD
      requests.

PMID- 9652260
TI  - Evidence for the effectiveness of cardiac rehabilitation.
AB  - Cardiac rehabilitation is a relatively recent development and, though it is
      increasingly being recognized as an important part of comprehensive cardiac care,
      there remains some scepticism regarding its effectiveness and some ignorance of
      its potential. This article reviews the literature pertaining to the
      effectiveness of cardiac rehabilitation for patients with coronary heart disease
      (CHD).

PMID- 9652261
TI  - Colony stimulating factors: G-CSFs--filgrastim (Neupogen) and lenograstim
      (Granocyte).
AB  - The introduction of leucocyte growth factors produced by DNA biosynthetic
      technology has had a major impact on survival in patients with compromised
      immunity. Such agents have maximized the benefits of treatment with drugs which
      are otherwise potentially toxic to the bone marrow.

PMID- 9652262
TI  - The impact of a hospital-wide experiential learning educational program on
      staff's knowledge and misconceptions about aging.
AB  - The increased use of health care services by older adults has prompted an
      interest in preparing health care workers to better deal with the special needs
      of older adults. Aging education is one method of sensitizing health care
      personnel to these special needs, but the effectiveness of such educational
      programs needs to be established. The purpose of this study was to examine the
      impact of the knowledge and attitudes of hospital personnel of their
      participation in an experiential learning educational program concerning older
      adults. Each of nine groups of hospital employees attended a 2-hour workshop.
      Each group completed a pretest and posttest using Palmore's Facts on Aging Quiz.
      A significant increase in scores was found in all groups after the workshop
      experience, and some groups had a greater increase in scores than others.

PMID- 9652263
TI  - Using role theory concepts to understand transitions from hospital-based nursing
      practice to home care nursing.
AB  - BACKGROUND: The phenomena experienced by professional nurses who make practice
      based career changes are seldom addressed in the literature. Nurses changing from
      a hospital-based practice to a home health care setting report feelings of
      anxiety, incompetency, and lack of the necessary skills to care for clients in
      the home. METHOD: An integrative review of the literature on role theory can
      provide the conceptual understanding of the transitional experience of nurses
      whose roles change when they move from hospital-based practice to a home health
      care setting. RESULTS: A model of the role transition process is helpful in
      identifying the transition experienced by nurses new to the home health care
      setting. Experiences during the initial transition period are critical in shaping
      the nurse's understanding of the role. CONCLUSION: Educators can play a key part
      in assisting novice home health care nurses with role enactment by developing
      comprehensive orientation and education programs aimed at minimizing role strain.

PMID- 9652264
TI  - The growth and development of an educational consortium.
AB  - This article discusses the beginning and continual evolution of a critical care
      educational consortium. Committee membership, curriculum development, and key
      service provisions are discussed. This article focuses on the process involved in
      the development of an educational consortium and the intended and unintended
      outcomes that developed as a result of this joint venture.

PMID- 9652265
TI  - Knowledge, perceptions, and practice of nurses toward HIV+/AIDS patients
      diagnosed with tuberculosis.
AB  - BACKGROUND: Tuberculosis (TB) continues to be a major health problem in the
      United States. Nurses may be exposed to TB and not realize their risks for
      becoming infected. The presentation of HIV-associated TB is somewhat different
      from "standard TB." PURPOSE: The purpose of this study was to determine if an
      educational program could improve nurses' attitudes, level of knowledge, and
      compliance with infection control standards for HIV/AIDS patients diagnosed with
      TB. METHOD: Participants included 50 staff nurses. The experimental group (35)
      and control group (15) completed a knowledge test and an attitude survey.
      Researchers observed participants for compliance with infection control standards
      pretest and posttest. RESULTS: Following an educational program, the experimental
      group demonstrated a greater knowledge of TB than the control group who did not
      participate in the educational program (F [1.47] = 14.43, p = .000). In addition,
      the experimental group had a greater improvement in their Nursing Intervention
      Observation Tool adherence to respiratory isolation and universal precaution
      protocols scores as compared to the control group (F [1.47] = 8.95, p = .004).
      However, there was not a tangible increase in knowledge level of AIDS, attitudes
      or concerns about caring for these patients. CONCLUSION: This nursing research
      study supports the need for an ongoing educational program with continual
      monitoring of infection control practices to positively affect client and
      caregiver outcomes.

PMID- 9652266
TI  - The patient care assistant program: the nursing profession's and a community
      college's response to educating unlicensed assistive personnel.
AB  - Preparing unlicensed assistive personnel for work in hospitals is one of the
      major challenges facing the nursing profession in the 1990s. Continued debate
      prevails over who should educate these health care workers and what content
      should be included in the curriculum. The 516-hour course described in this
      article was designed by nursing professionals to educate and train individuals to
      function as unlicensed assistive personnel in the acute care setting. The program
      takes place in a junior college and consists of learning activities in the
      classroom, skills laboratory, nursing home, and acute care hospital.

PMID- 9652267
TI  - Preparing nurses for the acute care case manager role: educational needs
      identified by existing case managers.
AB  - BACKGROUND: There is little in the literature about how best to prepare nurses
      for case manager roles. METHOD: Twenty acute care case managers were asked to
      identify skills and knowledge that would be of value to nurses new to case
      manager roles. RESULTS: Community resources, discharge planning, and third party
      reimbursement were the top three educational needs identified by all case
      managers. Baccalaureate prepared case managers identified clinical issues to be
      of value, such as family coping, patient education, quality of life, and social
      support, while master's prepared nurses identified only system-related issues.
      CONCLUSION: Educational programs preparing baccalaureate prepared case managers
      could focus on both clinical and system issues, while programs preparing master's
      educated case managers could focus primarily on managing system issues. Staff
      development professionals may also call on experts inside and outside the
      institution to assist in teaching about health care finance and reimbursement
      issues.

PMID- 9652269
TI  - Pediatric intravenous nursing.

PMID- 9652268
TI  - Integrating ongoing evaluation process for international pediatric nursing
      courses.
AB  - Two international pediatric courses for nurses from developing countries were
      planned and implemented in Israel during the past 2 years. The courses consisted
      of 53 RNs from 29 countries. The purpose of this article is to describe the
      ongoing evaluation and follow-up process of these courses. Findings indicated
      that the majority of nurses expressed: a) high satisfaction with the course and
      felt it enhanced their professional capacity and practice, and benefited their
      colleagues and superiors; b) high motivation and enthusiasm to improve nursing
      practices in their home countries; c) changes in attitudes and beliefs relating
      to pediatric nursing.

PMID- 9652270
TI  - Indiscriminate use of intravenous hydration in dying patients.

PMID- 9652271
TI  - Impact of dressing materials on central venous catheter infection rates.

PMID- 9652272
TI  - Pediatric growth hormone deficiency.
AB  - Current information on the pathophysiology, diagnostic process, and treatment of
      growth hormone deficiency is provided. A case study is provided that shows the
      positive effects of growth hormone therapy on a patient and his family.
      Information regarding the intravenous clinician's role in administration of
      growth hormone and patient teaching also is included.

PMID- 9652273
TI  - Emergency access in pediatrics.
AB  - Obtaining i.v. access in children during an emergency situation is a challenge to
      nurses. It is important for the infusion nurse specialist to understand which
      devices and sites are appropriate in different circumstances. This article
      addresses the access sites and devices demanded in pediatric emergency situations
      and offers an approach to managing the anxiety of children requiring emergency
      infusion care and their families.

PMID- 9652274
TI  - Fluid and electrolyte balance in the pediatric patient.
AB  - Maintaining adequate fluid and electrolyte balance is an important aspect of all
      patient care. The intravenous nurse's skill and expertise in starting and
      maintaining i.v. access is extremely vital to providing adequate fluids and
      electrolytes. Children and infants present unique problems in the management of
      fluid and electrolyte balance. Differences in rate of metabolism and body surface
      area are just two examples of special circumstances that affect diagnosis and
      management. An awareness of predisposing factors, early recognition of signs and
      symptoms that may be indicative of a developing problem, and knowledge of medical
      and nursing interventions help provide safe patient care. This article presents
      unique aspects of caring for infants and children, reviews important
      electrolytes, and discusses dehydration.

PMID- 9652275
TI  - Success rates for peripheral i.v. insertion in a children's hospital. Financial
      implications.
AB  - Although many publications have demonstrated the cost-effectiveness of using i.v.
      nurse specialists with adult patients, very few have explored this topic in the
      pediatric population. Many agencies choose to use staff RNs and physicians, with
      minimal training and experience, to place i.v.s in both pediatric and adult
      patients. This article demonstrates i.v. insertion success rates for various
      healthcare providers: staff RNs, physicians, and an i.v. nurse specialist in an
      urban pediatric hospital. The number of unsuccessful i.v. attempts for each group
      is calculated and further applied to costs of labor and equipment. From the data
      presented in this article, it may be concluded that the use of one or more i.v.
      specialist nurses for placement of peripheral i.v.s in children is more cost
      effective than using staff RNs or physicians for provision of this service. These
      data were collected while the author was the i.v. nurse clinician at St.
      Christopher's Hospital for Children in Philadelphia.

PMID- 9652276
TI  - Use of in-line filters in pediatric intravenous therapy.
AB  - This study arose from a need to justify the extensive use of in-line intravenous
      filters in an Australian pediatric teaching hospital. The incidence of septicemia
      was observed for two 12-month periods before and after the withdrawal of in-line
      i.v. filters from patients with central venous access devices. A total of 19,221
      i.v. days were monitored in 88 children in two 1-year periods. No significant
      differences were found in the incidence of septicemia between the children who
      had filters fitted and those who did not. As a result, the routine fitting of
      filters to i.v. lines infusing fluids filtered during manufacture under a laminar
      flow has been discontinued with significant cost savings.

PMID- 9652277
TI  - Children's drawings: an invaluable source of information for nurses.

PMID- 9652278
TI  - Infants with Down syndrome: a look at temperament.
AB  - INTRODUCTION: This research describes temperament characteristics of infants with
      Down syndrome who are 1 to 4 months old. In the literature children with Down
      syndrome have been stereotyped. It was hypothesized that temperament
      characteristics may be evident and unique in newborns with Down syndrome. METHOD:
      A standardized questionnaire, The Early Infancy Temperament Questionnaire, a
      cover letter, informed consent forms, and a brief explanation of the project were
      given to families with a newborn infant with Down syndrome. Thirty-two (families
      with infants with Down syndrome completed the study. RESULTS: Mean scores
      indicate that infants with Down syndrome are rated more active, less intense,
      more distractible, and have a tendency to demonstrate more approach behaviors
      compared with normally developing infants. Data suggest infants with Down
      syndrome have some unique characteristics but are more like their normally
      developing peers than different. DISCUSSION: Integration and mainstreaming of
      infants and children with Down syndrome emphasizes the need for nurse
      practitioners to appreciate the temperament characteristics of these infants.

PMID- 9652279
TI  - Parents' perceptions of medical diagnoses and related issues for their high-risk
      infants.
AB  - INTRODUCTION: The objectives of this study were (a) to compare maternal and
      paternal perceptions of infant medical diagnoses with hospital-chart diagnoses,
      (b) to examine whether parental perceptions of infant medical condition (using
      three variables) were related to eight other parental perceptions, and (c) to
      determine what medical diagnoses were associated with parental expectations that
      neonatal diagnoses were having current effects of would have future effects on
      their infant. METHOD: With a questionnaire format 76 parents reported information
      about medical diagnoses and their perceptions about eight other issues for their
      infants who had been hospitalized in an NICU. RESULTS: Parents reported
      approximately 62% of the medical diagnoses for their infants during NICU
      hospitalization; these significantly differed from hospital-chart diagnoses.
      Parents who reported current or future effects of neonatal diagnoses also (a) had
      fears for their infants while in the hospital or currently, (b) perceived
      prematurity as having current or future effects, (c) reported restrictions for
      their infants caused by neonatal diagnoses, and (d) gave less optimal ratings for
      their infants' current health status. Parents' perceptions of current or future
      effects of neonatal diagnoses appeared to be inaccurate given the actual
      diagnoses for their infants. DISCUSSION: The underreporting of diagnoses by
      parents raises several issues as to how accurately parents are perceiving their
      infants. Parents who perceived continued effects of neonatal diagnoses also had
      less optimal perceptions of other related issues. Parent's perceptions of
      continued effects of neonatal diagnoses appeared to be unwarranted with respect
      to the actual diagnoses assigned to their infants.

PMID- 9652280
TI  - Creating spaces that enhance nurse practitioner practice.
AB  - STUDY QUESTION: What barriers related to limitations of space or facilities do
      nurse practitioners (NPs) describe in association with their current practice?
      METHOD: This was a descriptive quantitative/qualitative study of 81 NPs in one
      Midwestern state with a survey instrument previously developed under the auspices
      of the Division of Nursing and the American Association of Colleges of Nursing
      regarding advanced practice nursing. RESULTS: Of 641 questionnaires mailed to the
      total number of prescribing NPs in the state, 372 (58%) were returned. Of that
      number, 81 (22%) indicated that space limitations were a barrier to practice.
      Seven themes emerged in qualitative analysis of their narrative descriptions of
      this barrier. DISCUSSION: Results of this study can assist NPs to articulate
      their space requirements and enhance existing spaces to better meet patient and
      NP needs.

PMID- 9652281
TI  - Child passenger safety.
AB  - Motor vehicle crashes are a leading cause of death and disability among children
      in the United States despite the fact that child safety seats and seat belts can
      provide effective protection against serious and fatal injuries. Many child car
      seats and safety restraints are being used incorrectly. In addition, recent
      fatalities associated with children and air bags have heightened awareness of
      child passenger safety issues. Pediatric nurse practitioners are in an excellent
      position to offer motor vehicle occupant prevention strategies to families
      through health education and anticipatory guidance.

PMID- 9652282
TI  - Parent's behaviors, knowledge, and beliefs related to unintentional firearm
      injuries among children and youth in the southwest.
AB  - INTRODUCTION: The purpose of this research study was to describe parents'
      behaviors, knowledge, and beliefs related to unintentional firearm injuries among
      children and youth. METHOD: A convenience sample of 80 parents whose children
      were attending one of six Kindercare Learning Centers in a Southwestern city was
      surveyed during the summer of 1995 to learn about their behaviors, knowledge and
      beliefs about unintentional firearm injuries among children and youth. Data on
      demographic characteristics, behaviors, knowledge, and beliefs, were collected
      with a questionnaire. RESULTS: Men and parents who had grown up with a gun in the
      house were more likely to be gun owners. Forty-eight percent of parents kept at
      least one gun in the home. Twenty-six percent of gun owners reported that the gun
      was loaded at all times, and 18% reported that a gun was kept within reach of a
      child. The most common reason given by parents for having a gun was for
      protection (61%). Only 8% of parents reported having discussed firearm safety
      with a health care worker. None of the parents had discussed firearm safety with
      a pediatrician. A test of knowledge about firearm injuries revealed some gaps in
      knowledge, with no significant differences between men and women or gun owners
      and non-gun owners. DISCUSSION: Results suggest that firearms in the home
      continue to pose a significant risk to children. Anticipatory guidance from NPs
      and pediatricians is needed to protect children from unintentional firearm
      injuries.

PMID- 9652283
TI  - Risky choices: the dangers of teens using self-induced abortion attempts.
AB  - Although researchers and practitioners alike have long been aware of the
      existence and dangers of self-induced abortions, virtually no research exists on
      this topic. This article describes methods of self-induced abortion from current
      and historical literature. A case study of an adolescent using quinine is
      discussed to highlight both the reasons some adolescents choose to self-abort and
      the possible dangers of using such methods. Serious risks to the adolescent are
      associated with any self-induced abortion attempt. Nurse practitioners are in a
      key position to assess an adolescent's risk factors for self-induced abortion
      attempts and to educate about the dangers of such attempts.

PMID- 9652284
TI  - Update on feeding babies solid food.

PMID- 9652285
TI  - Rewards.

PMID- 9652286
TI  - Acute abdominal pain: a challenge for the practitioner.

PMID- 9652287
TI  - Adolescent injury prevention.

PMID- 9652288
TI  - Hot issues for NPs in 1998.
AB  - Although it is unlikely that the legislative endeavors of 1996 and 1997 relating
      to the health care industry will be matched in 1998, implementing regulations of
      the Balanced Budget Act and the Health Insurance Portability and Accountability
      Act will predicate the successes or shortcomings of these new laws in 1998. It is
      important that NPs stay in close contact with their state legislators and
      Medicaid officers responsible for implementing the SCHIP. NPs should also closely
      track efforts at the Federal level to ensure inclusion of non-physician providers
      in legislation that is important to NPs, such as bans on "gag" clauses--a
      protection that should include all health care providers.

PMID- 9652289
TI  - The score on high-tech sports nutrition for adolescents.

PMID- 9652290
TI  - The stage is set for disease management and ESRD: can it succeed?

PMID- 9652291
TI  - How hospitals can adapt to managing ESRD patient care.

PMID- 9652292
TI  - Competing in the ESRD marketplace.

PMID- 9652293
TI  - A case rating approach to improving clinical outcomes in ESRD.

PMID- 9652294
TI  - A nephrologist's perspective. The Illinois Nephrology Alliance.

PMID- 9652295
TI  - A consultant's perspective. Renal care of Louisiana.
AB  - Much has been said regarding the evolution of managed care and what the ultimate
      impact of managed care will have on the renal industry. The members of NIPA,
      under the guidance of its Board of Directors, formed RenalCare of Louisiana in
      order that the nephrologists could take the lead in defining and monitoring the
      quality of care delivered to ESRD and pre-ESRD patients under an at-risk payment
      methodology. NIPA places its members in the "drivers seat" in the development and
      implementation of a renal disease management organization, and therefore, the re
      engineering of the renal delivery system in Louisiana will be headed by Louisiana
      nephrologists rather than for-profit dialysis chains.

PMID- 9652296
TI  - Assessing the value of blood volume monitoring to improve outcomes. A comparative
      observational study.

PMID- 9652297
TI  - Disease management of ESRD: a brave new world for product suppliers.

PMID- 9652298
TI  - HMOs and ESRD: a gloomy scenario.

PMID- 9652299
TI  - Inadequate funding from payers will doom ESRD capitation.

PMID- 9652300
TI  - Molecular and immunological characteristics of latex allergens.
AB  - Natural rubber latex proteins are a well-recognized cause of type-I allergic
      reactions that increasingly afflict health-care workers, housekeeping personnel,
      and other persons using latex gloves or latex products. More than a dozen
      individual latex allergens have been identified of which eight have received an
      international nomenclature designation. To study the biochemical and
      immunological properties in detail, it is desirable to clone and express each of
      these allergens. Proteins that are involved in rubber synthesis are most likely
      confined to latex whereas other enzymes, such as chitinases or glucanases, are
      also present in fruits and may account for the symptoms observed in the latex
      fruit syndrome. The available data on the molecular characterization of latex
      allergens presented here illustrate the importance of this research in the
      production of better diagnostic tests and, perhaps, tools for immunotherapy.

PMID- 9652301
TI  - Induction of tolerance via the respiratory mucosa.
AB  - Immunological tolerance is defined as a state of specific non-responsiveness to a
      particular antigen induced by previous exposure to that same antigen. The mucosal
      surfaces comprise the upper and lower respiratory tracts, the gastrointestinal
      tract and the urogenitary tract, and are a major site of antigenic challenge. The
      immune system associated with the mucosa has the extraordinary potential to
      discriminate between antigens that are harmless (e.g. inhaled and dietary
      antigens) and those that are associated with pathogens. Normally soluble proteins
      delivered through the mucosal surfaces do not elicit a strong systemic immune
      response but instead induce a transient local immune response that is replaced by
      long-term peripheral unresponsiveness this is termed mucosal tolerance. The
      phenomenon of oral tolerance is well established and considerable attention has
      focussed on defining the underlying mechanisms. However, only comparatively
      recently was the induction of tolerance via the respiratory mucosa described, and
      it is this form of mucosal tolerance which forms the basis of this review.

PMID- 9652303
TI  - Changes in blood leukocyte distribution during double-blind, placebo-controlled
      food challenges in children with atopic dermatitis and suspected food allergy.
AB  - BACKGROUND: The development of clinical reactions to food antigens is associated
      with cellular changes. The aim of this study was to determine whether the
      clinical outcome of double-blind, placebo-controlled food challenges would
      correlate with changes in blood leukocyte distribution. METHODS: Double-blind,
      placebo-controlled food challenges were performed in 17 children with atopic
      dermatitis sensitized to hen's egg or cow's milk and in 9 children with atopic
      dermatitis but not sensitized to food. Blood leukocyte distribution and
      lymphocyte subsets were determined prior to and 24 h after challenges. RESULTS:
      In food-sensitized children the numbers of leukocytes and lymphocytes decreased
      significantly after allergen challenge independent of the clinical outcome of the
      provocation (p < 0.002 in both cases). This decrease was seen in T (CD3+) and B
      (CD19+) cell subsets (p<0.007 and p<0.0005, respectively). The CD4/CD8 ratio
      increased (p<0.04). The number of memory cells (CD45R0) dropped (p<0.02 for CD4
      and p<0.004 for CD8) and there was a loss of L-selectin (p<0.003 for CD4 and
      CD8). No changes in thrombocytes, neutrophils, eosinophils and basophils were
      observed. None of these changes were seen in the sensitized patients during
      placebo challenges or in the non-sensitized group of children. CONCLUSION:
      Changes in the leukocyte distribution after allergen challenge seem to be
      associated with sensitization, but not with the clinical outcome of the oral food
      challenge. They reflect important changes in the immune system in response to
      allergens, but are not useful in monitoring double-blind, placebo-controlled food
      challenges.

PMID- 9652302
TI  - Bell peppers (Capsicum annuum) express allergens (profilin, pathogenesis-related
      protein P23 and Bet v 1) depending on the horticultural strain.
AB  - BACKGROUND: Little is known about the role of bell peppers in food allergy. We
      collected sera from 11 patients with food allergy to bell peppers to analyze bell
      pepper extracts for allergen composition. METHODS: Proteins of mature fruits of
      eight horticultural strains of bell peppers were extracted and tested with
      patients' sera for IgE binding and with monoclonal and polyclonal antibodies in
      immunoblot. RESULTS: Profilin was detected in bell pepper extracts by an anti
      celery profilin antibody. It showed high IgE binding activity in all extracts,
      which could be inhibited by recombinant birch pollen profilin. Anti-birch pollen
      monoclonal antibody BIP3, directed against birch pollen proteins between 30 and
      69 kD, bound to bell pepper antigens of comparable molecular weights. A homologue
      of the major birch pollen allergen Bet v 1 was detected in four of eight
      horticultural strains of bell peppers, and was shown to bind IgE in 1 of the 11
      patients. A 23-kD allergen of bell peppers was shown to correspond to the 23-kD
      major paprika allergen by IgE absorption experiments. Its N-terminal sequence
      showed 100% identity to P23 from tomatoes. CONCLUSION: The appearance of profilin
      in all and Bet v 1 in 50% of the tested horticultural strains indicates that bell
      peppers have to be considered potentially dangerous for Bet v 1- and profilin
      sensitized patients. Moreover, in 4 of 8 horticultural strains of bell peppers a
      homologue of the osmotin-like protein P23 from tomatoes is responsible for
      substantial IgE binding. Contact with Bet v 1 and P23 homologues in bell peppers
      can therefore be minimized by avoidance of the respective horticultural strains.

PMID- 9652304
TI  - Cytokine production by CD4+ and CD8+ T cells in mice following primary exposure
      to chemical allergens: evidence for functional differentiation of T lymphocytes
      in vivo.
AB  - It has been demonstrated previously that repeated exposure of mice to chemical
      allergens of different types results in the development of qualitatively
      divergent immune responses characterized by the production by draining lymph node
      cells (LNC) of distinct cytokine patterns. Chronic exposure of mice to contact
      allergens, such as 2,4-dinitrochlorobenzene (DNCB), resulted in the secretion by
      LNC of low or undetectable levels of interleukins 4 and 10 (IL-4 and IL-10), but
      comparatively high levels of interferon gamma (IFN-gamma); the latter cytokine
      being produced by both CD4+ and CD8+ cells. In contrast, chronic exposure of mice
      to trimellitic anhydride (TMA), a respiratory allergen associated in humans with
      occupational asthma, induced instead the production by LNC of relatively high
      concentrations of IL-4 and IL-10, but little IFN-gamma. The low levels of IFN
      gamma secretion which were provoked by treatment with TMA were shown to derive
      from CD8+ cells exclusively. In the present investigations we have sought to
      determine whether the polarized responses observed following repeated exposure to
      these chemical allergens are reflected by cytokine secretion patterns provoked by
      primary exposure. To this end, mice of BALB/c strain were exposed epicutaneously
      daily for 3 consecutive days to concentrations of DNCB and TMA (1 and 10%,
      respectively), or to oxazolone, another contact allergen (0.25%), that resulted
      in substantial proliferative activity in draining lymph nodes. The production by
      draining LNC of IFN-gamma and of mitogen-inducible IL-4 was measured by enzyme
      linked immunosorbent assay and the relative contribution of CD4+ and CD8+ cells
      to the patterns of cytokine secretion observed was analyzed using both positive
      and negative selection methods. It was found that primary exposure to DNCB,
      oxazolone and TMA each resulted in the production by LNC of both IFN-gamma and IL
      4. Selective depletion of, or enrichment for, CD4+ and CD8+ cells revealed that
      only CD4+ cells elaborated mitogen-inducible IL-4. Depletion of neither CD4+ nor
      CD8+ cells compromised the production by TMA- or DNCB-activated LNC of IFN-gamma,
      although positively selected CD8+ cells were considerably less able than CD4+
      cells to elaborate this cytokine, presumably secondary to a lack of appropriate
      accessory cells. Taken together the results demonstrate that early during immune
      responses to DNCB or oxazolone and TMA there is no evidence for the selectivity
      of cytokine secretion patterns that characterizes responses following more
      chronic exposure. Moreover, it is clear that exposure to TMA initially induces
      the production of IFN-gamma by both CD4+ and CD8+ cells, whereas after more
      chronic treatment the secretion of this cytokine is a function of CD8+ cells
      exclusively. Collectively, these results indicate that the polarized responses
      that develop in mice following chronic exposure to different classes of chemical
      allergen are not reflected by the characteristics of primary immune responses. As
      such the development of qualitatively divergent immune responses to chemical
      allergens provides a paradigm for the evolution of differentiated T cell function
      with time and/or with antigen exposure.

PMID- 9652305
TI  - Diesel exhaust inhalation enhances airway hyperresponsiveness in mice.
AB  - BACKGROUND: Repeated intratracheal instillation of diesel exhaust particles and
      ovalbumin-induced airway hyperresponsiveness and airway inflammation in mice.
      However, the effects of daily inhalation of diesel exhaust may differ from the
      effects of direct instillation. METHODS: Therefore, mice were exposed to diesel
      exhaust by inhalation 12 h per day for 3 months. Before the diesel exhaust
      exposure, ovalbumin was injected intraperitoneally as a sensitization. After 3
      weeks of diesel exhaust exposure, these mice were challenged with ovalbumin every
      3 week thereafter. RESULTS: Diesel exhaust exposure with antigen challenge
      induced airway hyperresponsiveness and airway inflammation which was
      characterized by increased numbers of eosinophils and mast cells in lung tissue.
      The recruitment of inflammatory cells was accompanied by an increment in goblet
      cells on bronchial epithelium. Diesel exhaust exposure alone also enhanced airway
      hyperresponsiveness, but did not induce eosinophilic infiltration and/or an
      increment in goblet cells. CONCLUSION: Diesel exhaust inhalation enhanced airway
      hyperresponsiveness and airway inflammation caused by ovalbumin sensitization in
      mice.

PMID- 9652306
TI  - Contractile responses to allergen and cholinergic stimulation in bronchus and
      trachea of cockroach allergen-sensitized guinea pigs.
AB  - Airway hyperreactivity is a hallmark of asthma. Yet, the role of allergic
      sensitization in the hyperreactivity remains controversial. This study examined
      the effects of airborne cockroach allergen (CRa) sensitization on the
      contractility of bronchial (BSM) and tracheal (TSM) smooth muscle rings to
      cholinergic stimulations, and to specific antigen, in vitro. Guinea pigs were
      actively immunized with CRa, 5 mg (high dose, HD), 0.5 mg (low dose, LD), or
      saline aerosols (2x/day, 5 days/week, for 4 weeks) and challenged by CRa
      inhalation 5 days after last exposure. Twenty-four hours postchallenge, the
      contractions of the TSM and BSM to electrical field stimulation (EFS),
      acetylcholine (ACh), and to CRa were measured in vitro. In addition, the
      contraction to these stimuli were also examined in the passively sensitized TSM
      with the sera of CRa-immunized guinea pigs. The contractile responses of actively
      immunized and passively sensitized tissues to EFS and ACh were very similar to
      those of control tissues. CRa induced dose-dependent contractions in both
      actively immunized and passively sensitized, but not in control, tissues. The CRa
      induced contraction was stronger in the HD group than in the LD group (p<0.0001).
      Leukotriene C4/D4 receptor antagonist LY-171883 inhibited the CRa-induced
      contraction by 86% in actively immunized TSM, and by 9% in the passively
      sensitized TSM. Pyrilamine inhibited the contraction by 57% in actively immunized
      TSM and 70% in passively sensitized TSM. The results indicate that CRa
      sensitization does not cause increased airway smooth muscle contractility to
      cholinergic stimulations, but induces antigen-specific contractions in vitro.
      Leukotrienes appear to play a significant role in the CRa-specific contractions,
      more in the actively immunized than those in the passively sensitized tissues,
      while histamine exerts a moderate effect on the CRa-induced contractions.

PMID- 9652307
TI  - Inhibitory effects of lodoxamide on eosinophil activation.
AB  - Recent reports describe the beneficial use of lodoxamide, an anti-allergic
      compound, for the treatment of asthma and allergic conjunctivitis. Lodoxamide is
      known as a mast cell stabilizer, however, the association of a significant
      clinical improvement with a specific decrease in eosinophil infiltrate suggested
      possible direct effects of lodoxamide on eosinophils. The chemotactic response of
      eosinophils to fMLP as well as to IL-5, in vitro, was very significantly and dose
      dependently inhibited by Lodoxamide. Lodoxamide was also able to strongly inhibit
      the release of eosinophil peroxidase after IgA-dependent activation and, to a
      lesser extent, the release of eosinophil cationic protein and eosinophil-derived
      neurotoxin. Moreover, the release of cytotoxic mediators evaluated in an antibody
      dependent cytotoxicity assay against parasitic targets was also significantly
      reduced, not only in the case of human eosinophils but also in a rat eosinophil
      mast cell model of cytotoxicity. Taken together, these results indicate that
      lodoxamide can exert potent inhibitory effects on eosinophil activation in vitro
      combined with a strong inhibition of eosinophil attraction, leading therefore to
      a reduction in their pathological potential in vivo.

PMID- 9652308
TI  - Inhibition of neurotensin-stimulated mast cell secretion and carboxypeptidase A
      activity by the peptide inhibitor of carboxypeptidase A and neurotensin-receptor
      antagonist SR 48692.
AB  - BACKGROUND: Neurotensin (NT), a peptide found in brain and several peripheral
      tissues, is a potent stimulus for mast cell secretion and its actions are blocked
      by the specific NT receptor antagonist, SR 48692. Subsequent to stimulation, NT
      is rapidly degraded by mast cell carboxypeptidase A (CPA). In the experiments
      described here, we tested for the involvement of CPA activity in the activation
      of mast cell secretion by the peptide, NT. METHODS: Mast cells were isolated from
      the peritoneal and pleural cavities of rats, purified over metrizamide gradients
      and incubated at 37 degrees C in Locke solution or Locke containing the
      appropriate inhibitors. For some experiments, media derived from mast cells
      stimulated by compound 48/80 were used as a source of mast cell CPA activity.
      RESULTS: Treatment of mast cells with the highly specific peptide inhibitor of
      CPA derived from potato (PCI) inhibited histamine release in response to NT and
      NT8-13 (the biologically active region of NT). This inhibition required some 20
      min to develop and was only partially reversed by a 20-min wash period. PCI (10
      microM) did not inhibit histamine release in response to NT1-12, bradykinin,
      compound 48/80, the calcium ionophore, A23187, or anti-IgE serum. PCI also
      inhibited mast cell CPA activity. SR 48692, a highly selective antagonist of the
      brain NT receptor and of NT-stimulated mast cell secretion, also inhibited mast
      cell CPA activity as well as bovine pancreatic CPA activity in a concentration
      dependent manner. DISCUSSION: It is suggested that the mast cell binding site for
      NT and the active site for CPA may share similar characteristics. The results are
      discussed in terms of NT mechanism of action on the mast cell.

PMID- 9652309
TI  - Role of CD4+ and CD8+ T cells in regulating the chronic development of liver
      injury induced by delayed-type hypersensitivity to picryl chloride.
AB  - In this study we first investigated the cellular immune responses in mice with
      chronic liver injury induced by delayed-type hypersensitivity to picryl chloride
      (PCl). A continuous reduction, after week 3 of liver injury, was observed in the
      level of PCl-induced contact sensitivity but not in sheep red blood cell-induced
      footpad reaction, suggesting the presence of PCl-specific suppression. When
      spleen cells from mice whose liver had been injured for 1 week were systemically
      transferred into syngeneic recipients with the liver injury, the elevation in
      serum lactic dehydrogenase and the decrease in alkaline phosphatase and albumin
      levels in recipient mice were significantly exacerbated. However, when the liver
      damage in the donor mouse was allowed to proceed for 3, 5 or 7 weeks, biochemical
      changes in recipients were reduced to near normal levels. A flow-cytometric assay
      demonstrated that the number of CD4+ T cells in both spleen cells and liver
      nonparenchymal cells decreased dramatically during the late phase of liver
      injury, while CD8+ counts did not. These findings suggest that CD4+ and CD8+ T
      lymphocytes may contribute to the positive and negative regulation, respectively,
      of the early and late phases in the chronic development of liver injury.

PMID- 9652310
TI  - Seasonal chronic cough with sputum eosinophilia caused by Trichosporon cutaneum
      (Trichosporon asahii).
AB  - The case of a 46-year-old man with a chronic cough with sputum eosinophilia
      (atopic cough) caused by Trichosporon cutaneum serotype II (Trichosporon asahii)
      is reported. The diagnosis was made with the inhalation challenge test with T.
      asahii antigen. He was admitted for the diagnosis and treatment of a severe
      nonproductive cough in the summer season. Although his sputum contained 13%
      eosinophils of nucleated cells, he did not have bronchial hyperresponsiveness to
      methacholine or a heightened bronchomotor tone. Bronchodilator therapy was not
      effective for his cough. His symptoms worsened on returning home, suggesting the
      existence of some etiologic agent in his house. A high titer of serum anti
      Trichosporon antibody was detected and antigen provocation test with the
      Trichosporon extract was positive: the development of a cough 6 h later and a
      decrease in the cough threshold to inhaled capsaicin 48 h later (7.85 microM from
      31.3 microM prechallenge). This is the first report on a chronic cough with
      sputum eosinophilia induced by T. cutaneum (T. asahii).

PMID- 9652311
TI  - Mast cell, IgE and atherothrombosis.

PMID- 9652312
TI  - Echocardiographic assessment of right atrial function in patients with myocardial
      infarction with reference to obstructive lesions of the coronary arteries.
AB  - We assessed the relationship between right atrial (RA) function and obstructive
      lesions of the coronary arteries in 29 patients with recent or old myocardial
      infarction (MI). Patients were divided into 3 groups according to the location of
      obstructions as follows: obstruction at the proximal right coronary artery
      (segments 1 and 2) (RCA proximal group, n=9); obstruction at the distal RCA
      (segments 3 and 4) (RCA distal group, n=6); and obstruction at the left anterior
      descending coronary artery (LCA group, n=14). The RA volume and the fractional
      change in the RA area during atrial contraction (RA %AC) were evaluated by apical
      2-dimensional echocardiography. The right ventricular (RV) end-diastolic pressure
      (RVEDP) was measured in 4 patients in the RCA proximal group and 4 patients in
      the LCA group. The ejection fraction of the right ventricle (RVEF) was measured
      by radionuclide angiography or 2-dimensional echocardiography in 7 patients in
      the RCA proximal group, 5 patients in the RCA distal group, and 7 patients in the
      LCA group. The RVEF tended to be lower in the RCA proximal group than in the RCA
      distal and LCA groups. The RA volume was significantly greater in the RCA
      proximal group than in the LCA group. The RA %AC was significantly smaller in the
      RCA proximal group than in the RCA distal and LCA groups. There were no
      significant differences in the early diastolic RV inflow velocity among groups,
      but the late diastolic RV inflow velocity was significantly lower in the RCA
      proximal group than in the RCA distal and LCA groups. There was no significant
      difference in the RVEDP between the RCA proximal and LCA groups. Thus, RA
      dysfunction in the RCA proximal group appeared to be due to myocardial damage
      rather than to afterload mismatch. These findings suggest that RA dysfunction may
      occur in patients with an inferior MI who have an obstructive lesion of the
      proximal RCA.

PMID- 9652313
TI  - The relation between the pacing sites in the right ventricular outflow tract and
      QRS morphology in the 12-lead ECG.
AB  - Optimal pace mapping is a good predictor of the appropriate ablation site for
      idiopathic right ventricular tachycardia (VT) originating from the right
      ventricular outflow tract (RVOT). We studied the relationship between the RVOT
      pacing site and QRS morphology in the 12-lead ECG during pacing to find the
      optimal site more quickly. In 13 patients with idiopathic VT, pacing at 8 sites
      in the RVOT (free wall, septum, and anterior and posterior regions of upper and
      lower sites) was performed while 12-lead ECGs were recorded. The R-wave amplitude
      minus the S-wave amplitude in lead I (RI-SI) and aVF (RavF-SavF) and the
      transitional zone index (TZI) were compared in the different pacing sites; TZI
      was defined to examine the transitional zone as a value. The RI-SI was smaller in
      the anterior region than in the other regions, and the negative RI-SI predicted
      that the pacing site was in the upper or lower anterior regions. The RavF-SavF
      was larger in the septum and anterior regions than in the free wall and posterior
      regions. The TZI was larger in the free wall region than in the septum. From the
      results, we constructed a flow chart that differentiates the origin of the
      arrhythmia in the RVOT and a directional guide that indicates the direction from
      the current mapping site for optimal pace mapping. The results provided an ECG
      guide for locating the focus of VT originating from the RVOT. These findings may
      systematically improve the mapping procedure.

PMID- 9652314
TI  - Prognostic value of 1-day stress/rest electrocardiogram-gated single-photon
      emission computed tomography using Tc-99m-labeled methoxy-isobutyl isonitrile.
AB  - To evaluate the prognostic value of the simultaneous assessment of perfusion and
      left ventricular wall motion, exercise non-gated/rest electrocardiogram (ECG)
      gated 99mTc methoxy-isobutyl isonitrile (MIBI) single-photon emission computed
      tomography (SPECT) was performed in 182 patients suspected of having coronary
      artery disease. After injection of 250 MBq of 99mTc-MIBI at peak exercise, stress
      perfusion images were classified into 3 groups: normal, equivocal, and abnormal.
      Normal subjects completed the 1-day protocol but not the resting study, whereas
      patients with abnormal or equivocal perfusion images underwent ECG-gated SPECT
      study with injection of 750 MBq of 99mTc-MIBI 3 h later. Patients with normal
      perfusion during this protocol had a benign prognosis. Only 4 soft events
      occurred in the normal group (4.8%). In contrast, patients with both myocardial
      infarction and abnormal wall motion at rest experienced more cardiac events (7
      cardiac events including 1 cardiac death among a total of 45 patients; 15.6%,
      p<0.05 compared with normal subjects). In addition, ischemic patients also
      experienced more cardiac events (7 events including 2 cardiac deaths among a
      total of 25 subjects; 28.0%, p<0.01 compared with normal patients). Our data
      suggest that the simultaneous assessment of perfusion and wall motion by
      stress/rest ECG-gated 99mTc-MIBI SPECT is a reliable indicator of prognosis in
      patients suspected of having coronary artery disease.

PMID- 9652315
TI  - A psychobehavioral factor, alexithymia, is related to coronary spasm.
AB  - The aim of this study was to assess whether the psychobehavioral pattern
      alexithymia is related to coronary artery spasm. Alexithymia, deficient
      psychological awareness, was examined using the Minnesota Multiphasic Personality
      Inventory Alexithymia Scale in 100 patients with angina pectoris in whom coronary
      spasm, defined as > or = 99% coronary narrowing, was documented upon ergonovine
      provocation, and in 109 patients with chest pain syndrome who were shown to have
      almost normal coronaries without inducible coronary spasm on coronary angiogram
      (control group). Alexithymia was approximately twice as prevalent in the coronary
      spasm group (31%) as in the control group (14%) (p<0.01). Among various
      conventional risk factors including hyperlipidemia, obesity, diabetes mellitus,
      hypertension, hyperuricemia, or family history of ischemic heart disease, only
      male sex and smoking were more prevalent in the coronary spasm group than in the
      control group (p<0.001). The odds ratios of coronary spasm adjusted for all the
      other risk parameters including sex and age were 4.14 [95% confidence interval
      (CI) 1.81-9.47] for alexithymia and 2.38 (95, CI 1.18-4.82) for smoking. A
      psychobehavioral pattern, alexithymia, relates to coronary spasm. This
      relationship is independent of the conventional coronary risk factors.

PMID- 9652316
TI  - Early mortality after acute myocardial infarction: observational study in
      Yamagata, 1993-1995.
AB  - Although considerable information is available regarding the prognosis after
      acute myocardial infarction (AMI) in Western populations, little is known about
      the fate of Japanese subjects after AMI. The purpose of this study was to assess
      short-term mortality and factors influencing it after AMI in Japan. From April
      1993 to December 1995, 1,014 patients with AMI from 41 hospitals in Yamagata
      Prefecture were registered by cardiologists for the prospective survey. Among
      patients who died within 28 days after the onset of AMI, immediate causes of
      death were examined and the clinical profiles of these subjects were compared
      with those of patients that survived. Early death occurred in 184 patients (short
      term mortality 18%). Patients who died were significantly older than survivors
      (76.1+/-9.4 vs 67.6+/-11.8 years, p<0.01). They were also more likely to be women
      (50% vs 31%, p<0.01), to have had hypertension (64% vs 54%, p<0.05), diabetes
      mellitus (29% vs 20%, p<0.02), prior MI (17% vs 12%, p<0.05), or Killip class III
      or IV disease (63% vs 15%, p<0.01), and were significantly less likely to be
      current smokers (26% vs 45%, p<0.01) or to have been treated with reperfusion
      therapy (27% vs 63%, p<0.01). Multivariate logistic analysis demonstrated that
      independent predictors of early death were Killip class III or IV and advanced
      age. Reperfusion therapy was a negative predictor of death. Patients who died had
      arrived at hospital earlier than patients who survived. Mortality as a result of
      heart failure, cardiac rupture, or arrhythmia fell exponentially after the onset
      of AMI. Thus, the predictors of short-term mortality were similar to those
      reported in Western populations. More deaths occurred just after the onset of
      disease, suggesting that early therapy is important in reducing short-term
      mortality.

PMID- 9652317
TI  - Circadian variation in plasma levels of free-form tissue factor pathway inhibitor
      antigen in patients with coronary spastic angina.
AB  - Tissue factor pathway inhibitor (TFPI) is known to inhibit the initial reaction
      in the tissue factor-mediated coagulation pathway. We measured plasma free-form
      TFPI antigen levels and monitored 24-h Holter recordings at 06.00, 14.00 and
      22.00 h in 15 patients with coronary spastic angina, 13 patients with stable
      exertional angina, and 11 control subjects. There was a significant circadian
      variation in plasma free-form TFPI antigen levels in patients with coronary
      spastic angina (25.8+/-2.0 ng/ml at 06.00 h, 21.1+/-1.6 ng/ml at 14.00 h, and
      20.2+/-1.4 ng/ml at 22.00 h; p<0.01). Furthermore, free-form TFPI antigen levels
      at 06.00 h were significantly higher in coronary spastic angina patients than in
      patients with stable exertional angina or control subjects (p<0.01). Free-form
      TFPI antigen levels increased after the ischemic attacks in coronary spastic
      angina (p<0.01). This circadian variation correlated with the frequency of
      attacks, with the peak level occurring between midnight to early morning in
      patients with coronary spastic angina.

PMID- 9652318
TI  - The correlation between coronary stenosis index and flow-mediated dilation of the
      brachial artery.
AB  - We examined the relationship between flow-mediated dilation (FMD) of the brachial
      artery and the extent and severity of coronary artery disease (CAD). Using high
      resolution ultrasonography, we measured FMD and nitroglycerin-induced brachial
      artery dilation. We studied 121 patients (77 men, 44 women; mean age 64+/-11
      years, range 25-79 years) who underwent coronary arteriography. The extent and
      severity of CAD were assessed by the coronary stenosis index (CSI). The adjusted
      FMD correlated inversely with CSI (rs=-0.63, p<0.0001). Multivariate analysis
      demonstrated that the adjusted FMD was an independent predictor of CSI. The
      adjusted FMD was 10.2+/-4.8% in patients without CAD (n=32), 7.7+/-6.0% in
      patients with single-vessel disease (n=31), 5.2+/-5.5% in patients with double
      vessel disease (n=29), and 2.0+/-3.9% in patients with triple-vessel disease
      (n=29). The adjusted FMD was significantly lower in the double- (p<0.01) and
      triple-vessel (p<0.0001) disease groups than in patients without CAD. The
      adjusted FMD was significantly lower in the triple-vessel disease group than in
      the single-vessel disease group (p<0.001). Based on our results, as coronary
      atherosclerosis becomes more severe, the adjusted brachial artery FMD becomes
      more severely impaired.

PMID- 9652319
TI  - Validity of a self-administered diet history questionnaire for assessment of
      sodium and potassium: comparison with single 24-hour urinary excretion.
AB  - We developed a self-administered diet history questionnaire (DHQ) for use in
      prevention and control of cardiovascular diseases and cancer, and validated it by
      comparison with single 24-h urinary excretion of sodium (Na) and potassium (K).
      The subjects were 154 male and 69 female freshmen university students. Mean
      intakes (mmol/day) assessed by DHQ and the urinary excretion of Na were 196 and
      165 respectively for men and 179 and 136 respectively for women. Those of K were
      61.5 and 43.9 respectively for men and 56.8 and 41.6 respectively for women. The
      ratios of urinary excretion to dietary intake of Na were 0.97 in men and 0.84 in
      women. Those of K were 0.78 in men and 0.80 in women. The results for both Na and
      K were reasonable, except for Na in men. When Pearson correlation was examined
      between dietary and urinary Na and K, no significant correlations for Na in men
      (r=0.14) or women (r=0.23, p=0.06), or significant correlations for K in men
      (r=0.34, p<0.001) or women (r=0.40, p<0.001) were observed. The results suggest a
      reasonable ability to estimate a subject mean for Na in women, K in both sexes,
      and individual level for K for both sexes. The validity for individual level for
      Na intake is not conclusive because the duration of urine collection was too
      short.

PMID- 9652320
TI  - Doppler echocardiographic assessment and cardiac gene expression analysis of the
      left ventricle in myocardial infarcted rats.
AB  - The purpose of this study was to examine cardiac geometry and function by Doppler
      echocardiography and to analyze mRNA expression of cardiac phenotype and
      extracellular matrix in myocardial infarcted rats. Doppler echocardiograms and
      hemodynamics were measured 2 weeks after myocardial infarction (MI). mRNA levels
      in the non-infarcted left ventricle (LV) and infarct site were measured by
      Northern blot analysis. LV internal diastolic dimension was greater in infarcted
      (MI) than in sham-operated rats (control) (MI 7.2+/-0.3 mm vs control 4.6+0.3 mm,
      p<0.01). The fractional shortening decreased in MI rats (MI 32+4% vs control 61+/
      3%, p<0.01). Peak early filling velocity increased in MI rats (MI 91+/-5 cm/sec
      vs control 72+/-4 cm/sec, p<0.05), and deceleration rate of the early filling
      wave was more rapid in rats with MI (MI 25.1+/-2.8 m/sec2 vs control 12.4+/-1.7
      m/sec2, p < 0.01). Late filling velocity decreased (MI 16+/-3 cm/sec vs control
      35+/-6 cm/sec, p <0.05), resulting in a marked increase in the ratio of early
      filling to late filling (MI 7.1+/-1.2 vs control 2.5+/-0.4, p<0.01). mRNA levels
      for beta-myosin heavy chain (beta-MHC), a-skeletal actin, atrial natriuretic
      polypeptide (ANP), collagen types I and III, and matrix metalloproteinase 2 (MMP
      2) in the non-infarcted LV increased significantly by 1.8-, 2.4-, 4.7-, 2.6-, 2.1
      (all p<0.01) and 1.4-fold (p<0.05), respectively, compared with sham-operated
      myocardium. In the infarct site, mRNA levels for transforming growth factor (TGF)
      beta1, collagen types I and III, and MMP-2 significantly increased by 3.2-, 11.0
      , 9.7-, and 6.3-fold (all p<0.01), respectively, compared with sham-operated
      myocardium. Myocardial infarcted rat was characterized by cavity dilation and
      marked abnormalities of systolic and diastolic function, accompanied by a shift
      of myocytes to fetal phenotype and activation of collagen genes in the non
      infarcted myocardium.

PMID- 9652322
TI  - Alterations in sarcoplasmic reticulum and angiotensin II type 1 receptor gene
      expression after myocardial infarction in rats.
AB  - The purpose of this study was to investigate the function of sarcoplasmic
      reticulum (SR) and the role of angiotensin II type 1 receptor (AT1) in
      ventricular remodeling in non-infarcted areas after myocardial infarction (MI).
      MI was produced in anesthetized Sprague-Dawley rats (10-12-weeks old) by ligation
      of the left anterior descending coronary artery. Four weeks after MI, hemodynamic
      measurements were performed. SR Ca2+-ATPase activity and mRNA (SERCA2a) and AT1
      mRNA (AT1a, AT1b) were analyzed. Left ventricular end-diastolic pressure was
      higher and left ventricular dp/dt was significantly lower in the MI group. In non
      infarcted areas in the MI group, myocardial transverse diameter was significantly
      greater and both Ca2+-ATPase activity in the SR and SERCA2a level decreased. The
      AT1a level was higher in non-infarcted areas than in controls, whereas the AT1b
      mRNA expression level was unchanged. These results suggest that, in the
      ventricular remodeling after MI, alterations in SR protein and its mRNA in non
      infarcted myocardium help initiate heart failure and that Ca overload caused by
      the up-regulation of AT1a mRNA is an important cause of alteration in SR
      function.

PMID- 9652321
TI  - Postrest shortening of the action potential duration in rabbits: in vitro and in
      vivo correlation.
AB  - Previous evidence has shown that the action potential duration of rabbit
      ventricular muscle cells shortens after a rest period (postrest shortening).
      However, there has not been much research on postrest shortening in the intact
      heart. We recorded transmembrane action potentials (TAPs) of isolated papillary
      muscle from rabbit ventricle with glass microelectrodes and monophasic action
      potentials (MAPs) of the rabbit left ventricular endocardium with contact
      electrodes. In the in vitro experiments, repetitive regular stimuli (S1) at a
      cycle length of 1 sec were followed by a single extrastimulus (S2) at coupling
      intervals (S1S2) ranging between 0.5 sec and 8 sec. The increase in the S1S2
      interval resulted in a progressive shortening of the duration of TAP elicited by
      the S2, which was abolished by the simultaneous application of 1 mmol/L 4
      aminopyridine and 2 micromol/L ryanodine. In the in vivo experiments, regular
      right ventricular pacing (S1) at a cycle length of 0.35 sec was followed by a
      single extrastimulus (S2) with coupling intervals (S1S2) ranging between 0.25 sec
      and 3 sec. The increase in the S1S2 interval also resulted in a progressive
      shortening of the duration of MAP elicited by the S2. This is the first report to
      demonstrate postrest shortening in the intact heart, which probably occurs
      because of a mechanism analogous to that observed in the isolated ventricular
      muscle.

PMID- 9652323
TI  - Coronary-pulmonary artery fistulae depicted by multiplanar reconstruction using
      magnetic resonance imaging.
AB  - We compared the imaging capability of magnetic resonance angiography (MRA) with
      that of conventional coronary angiography in a patient with coronary-pulmonary
      fistulae. Using the latter procedure, it is difficult to measure abnormal
      tortuous blood vessels in one section. However, the course of blood vessels could
      be evaluated quite well by rearranging serial cross-sectional MRA images using
      multiplanar reconstruction (MPR). This procedure allowed us to determine the
      anatomic positional relationship of these vessels to the peripheral cardiac great
      vascular system. MPR may detect sites of influx and outflow of abnormal blood
      vessels.

PMID- 9652324
TI  - A case of cardiac sarcoidosis: significance of ventricular tachycardia
      originating from the septum.
AB  - A 65-year-old woman was admitted for assessment of recurrent tachycardia. Cross
      sectional echocardiography showed that the anterobasal portion of the ventricular
      septum was thin and dyskinetic. An electrophysiologic study revealed ventricular
      tachycardia, during which marked fragmented potentials could be obtained from the
      anterior septal aspect of the right ventricle. The site of earliest activation
      was in the vicinity of the His bundle. A diagnosis of cardiac sarcoidosis was
      made by based on endomyocardial biopsy combined with the clinical manifestations.
      Ventricular tachycardia originating from the anterior septum may be an indicator
      of underlying cardiac sarcoidosis.

PMID- 9652325
TI  - Use of temporary vena cava filters after catheter-directed fragmentation and
      thrombolysis in patients with acute pulmonary thromboembolism.
AB  - Acute pulmonary thromboembolism is a life-threatening disease and in almost all
      cases originates from deep venous thrombosis in the proximal deep venous system
      of the legs. In order to prevent further episodes of thromboembolism in 2
      patients with acute pulmonary thromboembolism, we inserted an Antheor temporary
      vena cava filter after catheter-directed fragmentation and thrombolysis. No
      complications occurred during the insertion of the filters and our results
      suggest that this filter device may be clinically safe and effective for
      temporary protection against pulmonary thromboembolism.

PMID- 9652326
TI  - Cardiac sarcoidosis mimicking hypertrophic cardiomyopathy: clinical utility of
      radionuclide imaging for differential diagnosis.
AB  - A 62-year-old woman with skin sarcoidosis was admitted to our hospital to
      ascertain whether she had cardiac involvement. Although she displayed no cardiac
      signs or symptoms, the electrocardiogram showed first-degree atrioventricular
      block, right bundle branch block with left anterior fascicular block, and giant
      negative T waves in the V3 lead. Echocardiography revealed marked hypertrophy
      localized in the basal portion of the interventricular septum (IVS) without
      systolic dysfunction, mimicking hypertrophic cardiomyopathy (HCM). Exercise
      thallium-201 myocardial imaging revealed redistribution in the anteroseptal
      region. Both gallium-67 (67Ga) and technetium-99m pyrophosphate (99mTc-PYP)
      scintigraphy revealed abnormal uptake in the myocardium. These findings
      disappeared after 2 months of steroid treatment. Reports of cardiac sarcoidosis
      mimicking HCM are rare. However, hypertrophy in the basal portion of the IVS is
      an important sign of early cardiac involvement in sarcoidosis. 67Ga and 99mTc-PYP
      scintigraphy were useful and necessary to differentiate this type of cardiac
      sarcoidosis from HCM.

PMID- 9652327
TI  - Preload and incident angle independent index of left ventricular contractility
      determined by continuous wave Doppler echocardiography.
AB  - Although left ventricular dP/dtmax can be accurately assessed using Doppler
      echocardiography, the fact that Doppler-derived dP/dtmax depends both on preload
      and Doppler incident angle limits its clinical value. We investigated the
      clinical usefulness of Doppler-derived (dP/dtmax)/IP (IP, isovolumic pressure),
      which is known to be relatively insensitive to preload and theoretically
      independent of the incident angle in 9 subjects. We conclude that Doppler-derived
      (dP/dtmax)/IP is relatively insensitive to both the incident angle and preload.
      In addition to its noninvasiveness, these unique features makes it very
      attractive as a clinical index of ventricular contractility.

PMID- 9652328
TI  - Birth insult alters ethanol preference in the adult rat.
AB  - While genetic factors clearly play a role in regulating ethanol intake, the
      present study considered the possibility that early environmental factors which
      influence central nervous system development and long-term function might also
      alter ethanol intake. The specific aim of the study was to test whether
      alterations in birth condition, namely Caesarean section (C-section) birth and C
      section birth with an added period of global anoxia, can affect subsequent
      ethanol preference in the adult rat. At 5 months of age, groups of experimental
      and vaginally born control rats were offered free choice between drinking water
      or various concentrations of ethanol (1-10% v/v) in water across 36 days of
      testing. Rats that had been born by C-section with 10 or 15 min of added global
      anoxia showed significant reductions in ethanol preference scores, in comparison
      to vaginally born controls. For the 10-min anoxia group, ethanol intake was
      decreased, water intake was increased and total fluid intake remained unchanged
      relative to values for vaginally born controls, across the entire test period.
      Although total fluid intake by the 15-min anoxia group also did not differ from
      that of vaginally born controls, the decreased ethanol preference scores in the
      15-min anoxia group were mainly due to increased water intake during some test
      periods and a combination of reduced ethanol intake and increased water intake
      during others. Animals born by rapid C-section alone, with no added period of
      global anoxia, showed reduced ethanol preference only during a few early periods
      of testing, a much less pronounced effect than that observed for animals with
      added global anoxia. When animals were given the choice between drinking water
      vs. solutions of sucrose or NaCl, no group differences due to birth condition
      were found on measures of sucrose or NaCl preference. Together with reduced
      ethanol preference, the 10-min anoxia group showed a transient depression of
      locomotor activity in response to a low dose (0.25 g/kg) of intraperitoneal
      ethanol, which had no effect on locomotion in vaginally born controls. These
      results indicate that a relatively subtle alteration in birth condition,
      compatible with grossly normal development and behavior, is sufficient to alter
      ethanol preference in the adult rat.

PMID- 9652329
TI  - Tachykinin NK1 receptor antagonists enhance stress-induced c-fos in rat locus
      coeruleus.
AB  - These experiments tested the hypothesis that substance P neurotransmission at
      tachykinin NK1 receptors in the locus coeruleus is involved in stress-induced
      activation of the locus coeruleus, using c-fos as an index of activation.
      Selective tachykinin NK1 receptor antagonists administered systemically did not
      result in substantial locus coeruleus c-fos expression. Restraint stress resulted
      in a large number of locus coeruleus c-fos expressing cells. Administration of
      two selective tachykinin NK1 receptor antagonists prior to restraint resulted in
      an increase in the number of locus coeruleus c-fos expressing cells, compared to
      restraint alone. These results suggest that the enhanced c-fos expression
      observed in response to tachykinin NK1 receptor antagonists combined with stress,
      could be due to the blockade of tachykinin NK1 receptor-mediated activity at
      sites other than the locus coeruleus, resulting in an overall activation of the
      locus coeruleus.

PMID- 9652330
TI  - Effects of yohimbine on naloxone-induced antinociception in a rat model of
      inflammatory hyperalgesia.
AB  - Effects of the alpha2-adrenoceptor antagonist yohimbine on the antinociception
      produced by a low dose of naloxone were examined in a rat model of carrageenan
      induced inflammation. In rats receiving saline prior to naloxone injection, the
      low dose of naloxone (5 microg/kg, i.p.) significantly prolonged paw withdrawal
      latency in response to noxious thermal stimuli for both the inflamed and the non
      inflamed paws 4 h after carrageenan injection (6.0 mg in 0.15 ml saline). In rats
      receiving yohimbine, the low dose of naloxone failed to produce prolongation of
      paw withdrawal latencies 4 h after carrageenan, whereas naloxone produced
      antinociception 7 days after carrageenan. The results suggest that noradrenergic
      mechanisms are involved in naloxone-induced antinociception only in the early
      phase of carrageenan-induced inflammation.

PMID- 9652331
TI  - Tension generation and increase in voltage-activated Na+ current by crotamine.
AB  - We performed the present experiments to study the action of crotamine, a toxin
      isolated from the venom of the South American rattlesnake, Crotalus durissus
      terrificus, on macroscopic Na+ currents in frog skeletal muscle by using the
      loose patch clamp technique. Crotamine at 50 microM increased the peak Na+
      current by 50% (P < 0.05). In addition, the voltage dependence of inactivation
      was shifted by +8 mV. Other parameters of Na+ currents (reversal potential,
      voltage-dependence of activation and time courses of inactivation, of activation
      and of removal of inactivation) were not significantly affected. We suggest that
      crotamine inhibits the direct transition of channels from closed to inactivated
      states, thereby forcing their transition through the open states.

PMID- 9652332
TI  - Bradykinin B2 receptors in nodose ganglia of rat and human.
AB  - The present study has employed in vitro electrophysiology to characterise the
      ability of bradykinin to depolarise the rat isolated nodose ganglion preparation,
      containing the perikarya of vagal afferent neurons. Both bradykinin and kallidin
      elicited a concentration-dependent (1-100 nM) depolarisation when applied to the
      superfusate bathing the nodose ganglia, whereas the bradykinin B1 receptor
      agonist, des-Arg9-bradykinin, was only effective in the micromolar range.
      Furthermore, the electrophysiological response to bradykinin was antagonised by
      the bradykinin B2 receptor antagonist, D-arginyl-L-arginyl-L-prolyl-trans-4
      hydroxy-L-prolylglycyl-3-(2-t hienyl)-L-alanyl-L-seryl-D-1,2,3,4-tetrahydro-3
      isoquinolinecarbonyl+ ++-L-(2alpha,3beta,7abeta)-octahydro-1H-indole-2-carbonyl-L
      arginine (Hoe 140), in a concentration-related manner. To determine the
      anatomical location of functional bradykinin B2 receptors, in vitro
      autoradiography with [125I]para-iodophenyl Hoe 140 was performed on sections of
      rat and human inferior vagal (nodose) ganglia and confirmed the presence of
      binding over vagal perikarya. Collectively, these data provide evidence for
      functionally relevant bradykinin B2 receptors on vagal afferent neurons, which
      are apparently also present on human vagal perikarya.

PMID- 9652333
TI  - Effects of chylomicrons and chylomicron remnants on endothelium-dependent
      relaxation of rat aorta.
AB  - The effects of chylomicrons and chylomicron remnants on endothelium-dependent
      relaxation of rat aorta were studied in vitro. Chylomicrons and chylomicron
      remnants were prepared in vivo. Aortic rings were incubated with the lipoproteins
      for 45 min before the vessels were constricted with phenylephrine and
      concentration relaxation response curves constructed to carbachol, ATP, A23187
      and S-nitroso-N-acetylpenicillamine. Maximum % relaxations to carbachol were
      significantly reduced by both chylomicrons and chylomicron remnants but responses
      to ATP and S-nitroso-N-acetylpenicillamine were unaffected. In addition,
      chylomicrons significantly inhibited A23187-induced relaxation, causing an
      increase in the EC50 value. Chylomicron remnants cause selective inhibition of
      carbachol-induced relaxation suggesting an action at the receptor or G protein
      coupled component of the receptor-mediated activation of the L-arginine-nitric
      oxide pathway. Chylomicrons appear to be less selective in their inhibition of
      the endothelium-dependent relaxation. This study demonstrates that lipoprotein
      particles of dietary origin may cause endothelial cell dysfunction.

PMID- 9652334
TI  - Central cardiovascular effects of tacrine in the conscious dog: a role for
      catecholamines and vasopressin release.
AB  - Centrally acting cholinergic agents are currently reported to increase blood
      pressure in various species through the stimulation of muscarinic cholinoceptors.
      Moreover, several cardiovascular adverse effects have been reported from clinical
      studies. The aim of this study was to investigate the effects of tacrine, an
      acetylcholinesterase inhibitor which has been reported to have therapeutic
      potential in Alzheimer's disease, on blood pressure and two vasopressor systems
      (sympathetic and vasopressinergic) in Beagle dogs. Intravenous (i.v.) tacrine (2
      mg kg(-1)) induced, in conscious and anesthetized dogs, an increase in systolic
      and diastolic blood pressure, accompanied by bradycardia. This increase was dose
      dependent with a peak effect at 1.5 min following administration. Tacrine also
      induced an increase in noradrenaline, adrenaline and vasopressin plasma levels.
      Pretreatment with the muscarinic receptor antagonist, atropine (2 mg kg(-1),
      i.v.), abolished the pressor response to i.v. injection of tacrine while
      pretreatment with the peripheral muscarinic receptor antagonist,
      methylscopolamine (0.2 mg kg(-1), i.v.), did not alter the increase in blood
      pressure. Similarly, noradrenaline and adrenaline changes in plasma levels were
      not modified by methylscopolamine but were abolished by atropine pretreatment. A
      similar tendency although not significant was observed for vasopressin plasma
      levels. The present results demonstrate that in dogs, tacrine (2 mg kg(-1), i.v.)
      stimulates central muscarinic cholinoceptors to increase blood pressure through
      activation of the two components of the sympathetic nervous system (i.e.,
      neuroneuronal noradrenergic and the neurohormonal adrenergic pathways) as well as
      through increasing noradrenaline, adrenaline and vasopressin plasma levels.

PMID- 9652335
TI  - In vivo and in vitro action of endothelin-1 on goat cerebrovascular bed.
AB  - This study concerned the effects and mechanisms of action of endothelin-1 on the
      cerebral circulation. Cerebral blood flow was electromagnetically measured in
      awake goats. Endothelin-1 (0.01-0.3 nmol) produced dose-dependent decreases in
      this flow (maximal reduction = 34%) and increases in cerebrovascular resistance
      (maximal increase = 74%) (P < 0.01). IRL 1620 (Suc-[Glu9, Ala11,15]endothelin-1
      (8-21), agonist for endothelin ET(B) receptors, 0.01-0.3 nmol) slightly decreased
      cerebral blood flow. The effects of endothelin-1, but not those of IRL 1620, on
      cerebral blood flow were diminished by 50% during infusion of the antagonist for
      endothelin ET(A) receptors, BQ-123 (cyclo-(D-Asp-Pro-D-Val-Leu-Trp), 2 nmol min(
      1)), but not affected during infusion of the antagonist for endothelin ET(B)
      receptors, BQ-788 (N-[N-[N-[(2,6-dimethyl-1-piperidinyl)carbonyl]-4-methyl-L
      Leucyl-1-(met hoxycarbonyl)-D-tryptophyl]-Dnorleucine monosodium), 2 nmol min(
      1)). Intravenous administration of NW-nitro-L-arginine methyl ester (L-NAME, 47
      mg kg(-1)) or NW-nitro-L-arginine (L-NNA, 47 mg kg(-1)) reduced basal cerebral
      blood flow by 39 and 33%, increased cerebrovascular resistance by 108 and 98% and
      mean arterial pressure by 23 and 17%, and decreased heart rate by 27 and 25%,
      respectively (all at least P < 0.05). The increases in cerebrovascular resistance
      (as absolute values) induced by endothelin-1 were not affected during either L
      NAME or L-NNA (as absolute values and percentages). Intravenous administration of
      meclofenamate (5 mg kg(-1)) did not change the cerebrovascular effects of
      endothelin-1 and IRL 1620. In isolated goat cerebral arteries under control,
      resting conditions, endothelin-1 (10(-11)-10(-7) M) induced concentration
      dependent contractions (EC50 = 4.78 X 10(-9) M; maximal contraction = 3177+/-129
      mg), whereas IRL 1620 (10(-11)-10(-7) M) produced no effect. This contraction
      produced by endothelin-1 was competitively blocked by BQ-123 (10(-7)-3 X 10(-6)
      M), and was not affected by BQ-788 (10(-6) and 10(-5) M). L-NAME (10(-4) M),
      meclofenamate (10(-5) M), indomethacin (10(-5) M), L-NAME (10(-4) M) plus
      meclofenamate (10(-5) M) and phosphoramidon (10(-4) M) did not affect the
      contraction in response to endothelin-1. Endothelium removal increased the
      response to endothelin-1, as well as the BQ-123 antagonism against endothelin-1
      (pA2 values, 7.62 vs. 6.88; P < 0.01). In both intact and de-endothelized
      arteries precontracted with prostaglandin F2alpha endothelin-1 induced a further
      contraction, and IRL 1620 caused no effect. These results suggest that: (1)
      endothelin-1 produces cerebral vasoconstriction by activating endothelin ET(A)
      receptors probably located in smooth muscle; (2) endothelin ET(B) receptors,
      nitric oxide and prostanoids might be not involved in the cerebrovascular action
      of endothelin-1, and (3) endothelium removal may increase cerebrovascular
      reactivity by increasing sensitivity of endothelin ET(A) receptors to endothelin
      1.

PMID- 9652336
TI  - Cardiovascular effects of verapamil enantiomer combinations in conscious dogs.
AB  - We examined the systemic and coronary hemodynamic effects of five combinations of
      R- and S-verapamil enantiomers (R/S; 100/0, 90/10, 80/20, 50/50, and 20/80%,
      respectively) in conscious dogs chronically instrumented for measurement of
      aortic and LV pressure, +dP/dt, subendocardial segment length, coronary blood
      flow velocity, and aortic blood flow. Dogs received escalating doses (0.1, 0.2,
      and 0.4 mg kg(-1)) of each verapamil combination over 2 min at 30 min intervals
      on different experimental days and peak changes in hemodynamics were recorded 2
      min after each dose. All verapamil combinations increased heart rate, mean aortic
      blood flow, and coronary blood flow velocity and decreased calculated systemic
      and coronary vascular resistance. Alterations in coronary hemodynamics were most
      pronounced with 20/80 R/S verapamil. Racemic and 20/80 R/S verapamil decreased
      mean arterial and left ventricular systolic pressure, in contrast to combinations
      with greater concentrations of the R enantiomer. Left ventricular function was
      unchanged during administration of 100/0, 90/10, and 80/20 R/S verapamil. Direct
      negative inotropic and lusitropic effects occurred with 50/50 and 20/80 R/S
      verapamil. The high dose of 20/80 R/S verapamil also increased left ventricular
      end-diastolic pressure and the regional chamber stiffness constant, consistent
      with diastolic dysfunction. The results indicate that combinations of R- and S
      verapamil produce differential hemodynamic and left ventricular functional
      effects in conscious, unsedated dogs that are dependent on the relative ratio of
      these enantiomers.

PMID- 9652337
TI  - Influence of beta-adrenoceptor agonists on the pulmonary circulation. Effects of
      a beta3-adrenoceptor antagonist, SR 59230A.
AB  - The aims of this study were (a) to compare in the rat isolated perfused lung
      preparation, the effects of isoprenaline and of three beta3-adrenoceptors
      agonists, SR 59104A, (N-[(6hydroxy-1,2,3,4-tetrahydronaphtalen-(2 R)-2yl)methyl]
      (2R)-2-hydroxy-2-(3-chlorophenyl)ethanamine hydrochloride), SR 59119A (N[(7
      methoxy-1,2,3,4-tetrahydronaphtalen-(2R)-2yl)methyl]-( 2R)-2-hydroxy-2-(3
      chlorophenyl)ethanamine hydrochloride) and SR 58611A (ethyl?(7S)-7-[(2R)-2-(3
      chlorophenyl)-2-hydroxyethylamino]-5,6,7, 8-tetrahydronaphtalen-2-yloxy?acetate
      hydrochloride) on hypoxia-induced pulmonary vasoconstriction, and (b) to
      investigate the potential existence of atypical beta-adrenoceptors in these
      effects. Propranolol (0.1 microM) was used to antagonize beta1- and beta2
      adrenoceptors whereas SR 59230A, 3-(2-ethylphenoxy)-1-[(1S)-1,2,3,4
      tetrahydronapht-1-ylam ino]-(2S)-2-propanol oxalate) (0.3 microM) was used to
      block beta3-adrenoceptors. Isoprenaline and the three beta3-adrenoceptors
      agonists caused concentration-dependent relaxations during the pulmonary pressure
      response. Propranolol and SR 59230A inhibited the relaxant effects of
      isoprenaline. SR 59230A but not propranolol inhibited those of SR 59104A.
      Finally, propranolol and SR 59230A failed to oppose SR 59119A- and SR 58611A
      induced relaxant effects. In concentrations > or = 1 microM, SR 59230A caused per
      se a relaxation of the hypoxic vasoconstricted lung. These results suggest the
      existence of atypical beta-adrenoceptors in the rat pulmonary vessels.

PMID- 9652338
TI  - Cardioprotective effects of quinapril after myocardial infarction in hypertensive
      rats.
AB  - Although angiotensin-converting enzyme inhibitors are beneficial for patients
      with congestive heart failure, the appropriate timing and dosage in acute
      myocardial infarction are still controversial. We examined the hemodynamic
      effects of quinapril administered before acute myocardial infarction in
      spontaneously hypertensive rats (SHR). Quinapril (10 mg/kg per day in drinking
      water) was started 1 week before infarction and continued for 4 weeks after
      infarction (total duration 5 weeks). The hemodynamic parameters were evaluated by
      cardiac catheterization 4 weeks after coronary ligation. Sham-operated SHR served
      as controls. After infarction, left ventricular end-diastolic and right atrial
      pressures were increased (P < 0.01) and blood pressure and cardiac index were
      decreased (P < 0.01); the magnitude of blood pressure reduction was similar in
      the treated and untreated rats with infarction. Quinapril improved these
      hemodynamic parameters significantly and decreased left and right ventricular
      weight. These results suggest that a prior treatment with quinapril in SHR with
      acute myocardial infarction is hemodynamically beneficial.

PMID- 9652339
TI  - Respiratory effects of glutamate receptor antagonists in neonate and adult
      mammals.
AB  - We determined the conditions (immaturity, species, anesthesia, receptor blockade
      selectivity) under which glutamate receptor blockade produces respiratory
      depression in mammals. In unrestrained 0- to 2-day-old neonate and adult mice and
      cats, ventilation was measured by the barometric method, before and after
      separate or sequential administration of a non-NMDA receptor antagonist, NBQX
      (2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline, 2-200 mg kg(-1) in mice,
      10-40 mg kg(-1) in cats), and a NMDA receptor antagonist, dizocilpine (3 mg kg(
      1) in mice, 0.15-1.0 mg kg(-1) in cats). NBQX or dizocilpine alone did not
      decrease ventilation in awake adults, but NBQX strongly depressed ventilation in
      neonate awake mice and in adult anesthetized animals. Given together, dizocilpine
      and NBQX always profoundly depressed ventilation by producing a lethal apnea in
      neonate mice, and an apneustic pattern of breathing in adults of both species and
      in neonate cats. We conclude that blockade of either NMDA or non-NMDA receptors
      is innocuous in awake adults. The factors which may potentiate respiratory
      depression are (1) anesthesia, (2) immaturity, and (3) combined blockade of both
      receptors types. The mechanism of depression is species-dependent and age
      dependent.

PMID- 9652340
TI  - Nitric oxide enhances prostaglandin production in ethanol-induced gastric mucosal
      injury in rats.
AB  - The interaction between endogenous nitric oxide (NO), elicited by administration
      of Escherichia coli lipopolysaccharide, and cyclooxygenase system, in ethanol
      induced injury in rat gastric mucosa, was investigated. Administration of graded
      doses of lipopolysaccharide reduced the gastric mucosal injury in response to
      ethanol. The ex vivo production of both nitrite and prostaglandin E2 was
      increased in dose-related manner by lipopolysaccharide. Pretreatment with
      dexamethasone, L-N6-(1-Iminoethyl)lysine(dihydrochloride) and L-NG-nitro arginine
      methyl ester inhibited the protection associated with lipopolysaccharide
      treatment and the ex vivo production of both, nitrite and prostaglandin E2. The
      pretreatment with L-arginine counteracted the decrease of nitrite and
      prostaglandin E2 production in lipopolysaccharide-treated rats in which nitric
      oxide synthesis was blocked by L-N6-(1-Iminoethyl)lysine(dihydrochloride).
      Administration of sodium nitroprusside and S-nitroso-N-acetyl-D,L-penicillamine
      caused a dose related enhancement in the accumulation of prostaglandin E2.
      Indomethacin administration and N-(2-Cyclohexyloxy-4
      nitrophenyl)methanesulfonamide were ineffective in suppressing lipopolysaccharide
      mediated protection against ethanol-induced damage, and in suppressing ex vivo
      increase of nitrite whereas the ex vivo increase of prostaglandin E2 was
      prevented in a dose-related fashion. These results indicate that in ethanol
      induced rat gastric injury, endogenous NO elicited by lipopolysaccharide or
      released by NO donors is able to activate the cyclooxygenase pathway, and the
      protective effect of lipopolysaccharide is dependent upon NO formation.

PMID- 9652341
TI  - Prostaglandin, tumor necrosis factor alpha and neutrophils: causative
      relationship in indomethacin-induced stomach injuries.
AB  - Tumor necrosis factor alpha (TNF-alpha) has been suggested to play a critical
      role in indomethacin-induced gastric mucosal damage, so we evaluated its mucosal
      level and its relationship with prostaglandin E2 and neutrophils in indomethacin
      induced gastric mucosal injury in rats. Indomethacin caused a time- and dose
      dependent increase in gastric mucosal erosion, which was accompanied by a
      reduction in prostaglandin E2 followed by an increase in TNF-alpha level and
      neutrophil infiltration in the gastric mucosa. Pretreatment with exogenous
      prostaglandin E2 totally abolished indomethacin-induced gastric mucosal injury
      and the TNF-alpha increase. Depletion of neutrophils by methotrexate or reduction
      of TNF-alpha concentration by pentoxifylline markedly reduced indomethacin
      induced mucosal damage. Pentoxifylline but not methotrexate prevented the
      increase in mucosal TNF-alpha level induced by indomethacin. It is suggested that
      depletion of prostaglandin E2 followed by an increase of TNF-alpha production and
      neutrophil infiltration in the gastric mucosa are important sequential processes
      in indomethacin-induced ulceration. Prevention of one of these processes would
      inhibit ulcer formation.

PMID- 9652342
TI  - Pancreatic islet responsiveness to D-glucose after repeated administration of
      repaglinide.
AB  - The influence of three daily oral doses of repaglinide (1.0 microg/g body wt.) on
      plasma insulin and glucose concentrations, pancreatic islet insulin content and
      both protein biosynthesis and insulin release in isolated islets incubated for 90
      min in the presence of either 2.8 or 16.7 mM D-glucose was examined in both
      control and hereditary diabetic Goto-Kakizaki (GK) rats. In the control rats,
      repaglinide lowered the plasma glucose concentration, whilst failing to affect
      significantly the plasma insulin concentration or insulin/glucose ratio, 24 h
      after the last administration of the antidiabetic agent. Despite a severe
      decrease of islet insulin content, the ratio between insulin release and content
      was not altered in islets obtained from repaglinide-treated control rats and
      incubated in the presence of 16.7 mM D-glucose. Also the biosynthesis of islet
      peptides was increased at both low and high hexose concentrations. In GK rats,
      repaglinide administration affected neither plasma glucose nor insulin
      concentration, restored a normal value for the otherwise abnormally high basal
      insulin output, increased the 16.7 mM/2.8 mM ratio for insulin release, and again
      augmented protein biosynthesis at both low and high hexose concentrations. In
      both control and GK rats, the stress induced by bleeding and decapitation
      augmented plasma glucose concentration. This effect was more pronounced in GK
      than in control rats and, in the diabetic animals, coincided with a severe
      lowering of the plasma insulin/glucose ratio, suggesting a higher adrenergic
      sensitivity of islet cells in the GK than in control rats. The increased
      secretory responsiveness to glucose and increased biosynthetic activity found in
      islets from GK rats after repaglinide administration, are considered favourable
      attributes of this meglitinide analogue in the perspective of its use as an
      insulinotropic agent in noninsulin-dependent diabetes.

PMID- 9652343
TI  - A possible mechanism underlying corymine inhibition of glycine-induced Cl-
      current in Xenopus oocytes.
AB  - We previously reported that corymine, an alkaloid extracted from the leaves of
      Hunteria zeylanica native to Thailand, inhibited glycine-induced chloride current
      using a receptor expression model of Xenopus oocytes. In this study, we
      investigated the mechanism underlying the inhibitory action of this alkaloid on
      glycine current using the same model. Corymine inhibited glycine current in a
      noncompetitive fashion. Co-application with strychnine, a competitive glycine
      receptor antagonist, or 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS),
      a Cl- channel blocker, corymine decreased the ED50 value of strychnine, but did
      not change that of DIDS. Moreover, the inhibitory effects of corymine and either
      strychnine or DIDS were additive. The desensitization phase of glycine current
      showed two exponentials and corymine preferentially inhibited the fast component,
      whereas strychnine affected both of them to the same extent and DIDS
      preferentially inhibited the slow component. When these drugs were applied
      repeatedly, the inhibitory effects of corymine and strychnine were not use
      dependent and reversible, while the effect of DIDS was use-dependent and
      irreversible. The inhibitory effect of corymine on gamma-aminobutyric acid (GABA)
      current was less potent than the effect on glycine current, while this alkaloid
      failed to affect acetylcholine and serotonin currents. These results demonstrate
      that corymine inhibits glycine-gated CI- channels by interacting with the site
      different from that of DIDS.

PMID- 9652344
TI  - Human 5-HT1B receptor stimulated inositol phospholipid hydrolysis in CHO cells:
      synergy with Gq-coupled receptors.
AB  - We have previously reported that the transfected Gi/Go protein-coupled human
      adenosine A1 receptor (expressed at 200 fmol/mg of protein) and the endogenous 5
      HT1B receptor (not detectable using radioligand binding) suppress forskolin
      stimulated cyclic AMP accumulation and stimulate increases in [Ca2+]i in Chinese
      hamster ovary cells (CHO). In addition, co-activation of the adenosine A1
      receptor (but not the 5-HT1B receptor) potentiates the hydrolysis of inositol
      phospholipids elicited by receptors coupled to Gq-proteins (Dickenson and Hill,
      1996. Eur. J. Pharmacol. 320, 141-151). In order to establish whether this
      difference in ability to modulate Gq-coupled receptor responses is a consequence
      of low 5-HT1B receptor density, we have stably transfected CHO-KI cells with the
      human 5-HT1Dbeta cDNA (the human homologue of the rodent 5-HT1B receptor). We
      initially isolated a clonal cell line (designated CHO5-HT1B cells) displaying
      moderate specific [3H]5-HT binding (pKd of 8.17+/-0.07 and a Bmax of 140 fmol/mg
      protein). In CHO5-HT1B cells, the selective human 5-HT1B/1D receptor agonist
      sumatriptan produced a concentration-dependent inhibition of forskolin-stimulated
      cyclic AMP accumulation (pEC50=7.92+/-0.04). Sumatriptan also elicited a moderate
      and pertussis toxin-sensitive increase in [3H]inositol phosphate formation in CHO
      5HT1B cells (pEC50=6.51+/-0.05). Finally, sumatriptan synergistically enhanced
      P2U purinoceptor stimulated [3H]inositol phosphate accumulation through a
      pertussis toxin-sensitive mechanism. These findings clearly show the significance
      of 5-HT1B receptor expression level in determining whether 5-HT1B receptor
      activation can modulate the accumulation of [3H]inositol phosphates elicited by a
      Gq-protein coupled receptor. The observation that 5-HT1B receptor activation can
      potentiate Gq-coupled receptor stimulated second messenger responses may have an
      important physiological role in the regulation of vascular smooth muscle
      contraction.

PMID- 9652345
TI  - Characterization of specific binding of [125I]L-762,459, a selective alpha1A
      adrenoceptor radioligand to rat and human tissues.
AB  - L-762,459 ((+/-)1-(3-?[5-carbamoyl-2-2-[(4-hydroxy-3-iodobenzimidoyl)-amino] 
      ethoxy-methy?-6-methyl-4-(4-nitropheny)-1,4-dihydropyridine -3-carbonyl]-amino?
      propyl)-4-phenyl-1-piperidine-4-carboxylic acid methyl ester), an analog of a
      series of dihydropyridines previously reported to be selective alpha1A
      adrenoceptor subtype antagonists was found to have alpha1A-adrenoceptor subtype
      selectivity (Ki (nM), la = 1.3, lb = 240, Id = 280). Specific [125I]L-762,459
      binding was detected in rat cerebral cortex, hippocampus, vas deferens, kidney,
      heart and prostate tissues known to contain the alpha1A-adrenoceptor subtype, but
      not in tissues known to contain alpha1B-adrenoceptor (spleen, liver) and alpha1D
      adrenoceptor (aorta). Scatchard analysis of [125I]L-762,459 binding in rat
      cerebral cortex and prostate indicated a single binding site with a Kd of 0.7 nM
      and Bmax of 11 (cerebral cortex) and 1 (prostate) pmole/g tissue. Specific and
      saturable [125I]L-762,459 binding was also found in human cerebral cortex, liver,
      prostate and vas deferens (Kd = 0.2-0.4 nM, Bmax = 0.4-4 pmole/g tissue). The
      specific binding in rat and human tissues was competed by non-selective alpha1
      adrenoceptor compounds (Ki values in nM: prazosin (0.14-1.2), terazosin (1.8-5.9)
      and phentolamine (2.4-11)) and selective alpha1A-adrenoceptor compounds [Ki
      values in nM: (+) niguldipine (0.04-1.2) and SNAP 5399 ((+/-)-2-((2
      aminoethyl)oxy)methyl-5-carboxamido-6-ethyl-4-(4-nitropheny l)-3-N-(3-(4,4
      diphenylpiperidin-1-yl)propyl)carboxamido-1,4-dihyd ropyridine hydrate (0.5
      4.8)]. The results were consistent with the selective binding of [125I]L-762,459
      to the alpha1A-adrenoceptor. The specific labeling of the alpha1A-adrenoceptor
      subtype by [125I]L-762,459 may make it a useful tool to localize the distribution
      of the alpha1A-adrenoceptor.

PMID- 9652346
TI  - Fenspiride inhibits histamine-induced responses in a lung epithelial cell line.
AB  - Using the human lung epithelial WI26VA4 cell line, we investigated the capacity
      of fenspiride, an anti-inflammatory drug with anti-bronchoconstrictor properties,
      to interfere with histamine-induced intracellular Ca2+ increase and eicosanoid
      formation. Histamine and a histamine H1 receptor agonist elicited a rapid and
      transient intracellular Ca2+ increase (0-60 s) in fluo 3-loaded WI26VA4 cells.
      This response was antagonized by the histamine H1 receptor antagonist,
      diphenhydramine, the histamine H2 receptor antagonist, cimetidine, having no
      effect. Fenspiride (10(-7)-10(-5) M) inhibited the histamine H1 receptor-induced
      Ca2+ increase. In addition, histamine induced a biphasic increase in arachidonic
      acid release. The initial rise (0-30 s), a rapid and transient arachidonic acid
      release, was responsible for the histamine-induced intracellular Ca2+ increase.
      In the second phase release (15-60 min), a sustained arachidonic acid release
      appeared to be associated with the formation of cyclooxygenase and lipoxygenase
      metabolites. Fenspiride (10(-5) M) abolished both phases of histamine-induced
      arachidonic acid release. These results suggest that anti-inflammatory and
      antibronchoconstrictor properties of fenspiride may result from the inhibition of
      these effects of histamine.

PMID- 9652347
TI  - Endothelin-1-(1-31), a novel vasoactive peptide, increases [Ca2+]i in human
      coronary artery smooth muscle cells.
AB  - We have previously found that human chymase cleaves big endothelins at the Tyr31
      Gly32 bond and produces 31-amino acid long endothelins-(1-31), without any
      further degradation products. In this study, we investigated the effect of
      synthetic endothelin-1-(1-31) on the intracellular free Ca2+ concentration
      ([Ca2+]i) in cultured human coronary artery smooth muscle cells. Endothelin-1-(1
      31) increased [Ca2+]i in a concentration-dependent manner (10(-14) to 10(-10) M).
      This endothelin-1-(1-31)-induced [Ca2+]i increase was not affected by
      phosphoramidon (N-(alpha-Rhamnopyranosyloxyhydroxyphosphinyl)-L-Leucyl-L-Tryptoph
      an), an inhibitor of endothelin-converting enzyme. It was, however, inhibited by
      10(-10) M BQ123 (Cyclo-(-D-Trp-D-Asp(ONa)-Pro-D-Val-Leu-)), an endothelin ET(A)
      receptor antagonist, but not by 10(-10) M BQ788 (N-cis-2,6
      dimethylpiperidinocarbonyl-L-yMeLeu-D-Trp(COOM e)-D-Nle-ONa), an endothelin ET(B)
      receptor antagonist. These results suggest that endothelin-1-(1-31) by itself
      exhibits vasoactive properties probably through endothelin ET(A) receptors. Since
      human chymase has been reported to play a role in atherosclerosis, endothelin-1
      (1-31) may be one of the candidate substances for its cause.

PMID- 9652348
TI  - [125I][Tyr3]octreotide labels human somatostatin sst2 and sst5 receptors.
AB  - Human somatostatin (somatotropin release inhibiting factor = SRIF) receptor
      subtypes sst2 and sst5 were stably expressed in Chinese hamster lung fibroblast
      (CCL39) cells. [125I][Tyr3]octreotide labelled with high affinity and in a
      saturable manner both sst2 (pKd = 9.89+/-0.02, Bmax = 210+/-10 fmol/mg, n = 3)
      and sst5 sites (pKd = 9.64+/-0.04, Bmax = 920+/-170 fmol/mg, n = 3). The
      pharmacological profile of sst2 sites established in CCL39 cells using SRIF and
      various peptide analogues was very similar to that described previously in CHO
      cells and in human cortex: SRIF14 = SRIF28 > or = seglitide > BIM 23014 = RC 160
      > octreotide > CGP 23996 > or = L362,855 > BIM 23052 > L361,301 = cortistatin14 >
      BIM 23030 > BIM 23056 > cycloantagonist SA. However, peptides classically
      perceived as sst2 receptor selective (e.g., seglitide, octreotide, vapreotide)
      showed also high affinity for human sst5 receptors labelled with
      [125I][Tyr3]octreotide: SRIF28 > seglitide > SRIF14 > L361,301 = octreotide >
      cortistatin14 = BIM 23014 = BIM 23052 > L362,855 = RC160 > CGP 23996 > BIM 23056
      > cycloantagonist SA > BIM 23030. Further radioligand binding studies were
      performed with [Leu8,D-Trp22,125I-Tyr25]SRIF28 ([125I]LTT-SRIF28) and [125I]CGP
      23996. At sst2 receptors, Bmax values determined with [125I][Tyr3]octreotide,
      [125I]LTT-SRIF28 and [125I]CGP 23996 were in the same range (180-370 fmol/mg). 5'
      Guanylyl-imidodiphosphate (GppNHp) displaced all three radioligands to the same
      extent (85%) and the pharmacological profiles were superimposable. By contrast,
      at sst5 receptors Bmax values were very different: [125I][Tyr3]octreotide (920
      fmol/mg), [125I]CGP 23996 (3530 fmol/mg) and [125I]LTT-SRIF28 (6950 fmol/mg).
      GppNHp affected [125I][Tyr3]octreotide more than [125I]CGP 23996 binding, whereas
      [125I]LTT-SRIF28 was much less affected. In addition, the affinity values
      determined in competition experiments at sst5 receptors, varied markedly; whereas
      SRIF14, cortistatin14 and SRIF28 showed 2-, 4- and 8-fold differences in affinity
      at sst5 receptors labelled with [125I][Tyr3]octreotide and [125I]LTT-SRIF28
      compounds such as RC160, L363,301, L362,855, octreotide or CGP 23996 showed
      between 42- and 123-fold lower affinity when sst5 sites were labelled with
      [125I]LTT-SRIF28. The present data suggest caution to be used when comparing
      affinity profiles determined in binding studies using different radioligands. In
      addition, the present results suggest that effects produced by octreotide and
      related short chain SRIF analogues on hormone release, modulation of tumour
      growth and central effects may be mediated by either sst2 and/or sst5 receptors.

PMID- 9652349
TI  - Regulation of GABA(A) receptor alpha1 protein is a sensitive indicator of
      benzodiazepine agonist efficacy.
AB  - The effect of benzodiazepine agonists of varying efficacy on gamma-aminobutyric
      acidA receptor alpha1 subunit protein expression was determined in primary
      cultured cerebellar granule cells. After 48 h exposure to 1 microM drug
      concentrations, flunitrazepam, diazepam, and the partial agonists Ro 19-8022 and
      bretazenil, but not the partial agonists Ro 42-8773, Ro 41-7812 or imidazenil,
      decreased alpha1 subunit protein expression. The grading of effect of the
      benzodiazepine partial agonists on alpha1 subunit protein expression is
      consistent with their agonist efficacies. This model, therefore, appears to act
      as a sensitive indicator of benzodiazepine agonist efficacy with the ability to
      differentiate between partial agonists.

PMID- 9652350
TI  - Identification of adenylyl cyclase isoenzymes in CHO and B82 cells.
AB  - The identification of adenylyl cyclase isoenzymes in mammalian host cells is
      important for the interpretation of data obtained from cell lines heterologously
      expressing G-protein coupled receptors. Reverse transcriptase polymerase chain
      reaction (RT-PCR) was used to amplify adenylyl cyclase cDNAs from Chinese hamster
      ovary (CHO) and mouse fibroblast (B82) cells. The isolated fragments were
      identified by restriction analyses and by sequencing. We found mRNAs for adenylyl
      cyclases VI and VII in CHO and adenylyl cyclases IX and VII in B82 cells.

PMID- 9652351
TI  - Nicorandil affects diurnal rhythms of body temperature, heart rate and locomotor
      activity in rats.
AB  - The effects of nicorandil, a K+ channel opener with a potent vasodilator action,
      on diurnal rhythms of body temperature, heart rate and locomotor activity were
      assessed in rats. Transmitters were intraperitoneally implanted under ether
      anaesthesia. After recovery from surgery, body temperature, heart rate and
      locomotor activity were recorded during control, saline or nicorandil (10 mg x
      kg(-1) administered orally) treatment and for 5 days after treatment. For each
      period, Fourier analysis determined the predominant rhythmicity for body
      temperature, heart rate and locomotor activity while cosinor analysis assessed
      the corresponding mesors, acrophases and amplitudes and maxima and minima were
      directly plotted from raw data. The results indicated: (1) loss of the diurnal
      rhythmicity for all three rhythms after implantation; (2) stress-induced
      modifications of almost all the characteristics of the three rhythms after saline
      and (3) a loss of diurnal rhythmicity of heart rate after nicorandil, an effect
      that was not observed after saline and which was reversed when nicorandil
      administration was stopped. In conclusion, nicorandil perturbed the diurnal
      rhythmicity of heart rate while the rhythmicity of body temperature and locomotor
      activity was not affected.

PMID- 9652352
TI  - Pharmacokinetic-pharmacodynamic modeling of the coexistence of stimulatory and
      sedative components for midazolam.
AB  - Midazolam increased the shorter-response rate and decreased the reinforcement
      rate of a contingency-controlled timing behavior--a differential-reinforcement-of
      low-rate 45-s schedule. The responding rate changes observed were immediately
      interpretable as functions of midazolam concentration during a 3-h session--a
      period for investigating the onset, peak, and disappearance of midazolam effect-
      in rats. That the midazolam pharmacokinetic-pharmacodynamic model was a direct
      application of our alprazolam pharmacokinetic-pharmacodynamic model implies that
      both drugs exhibit similar pharmacological effects. The two peaks of the shorter
      response rate increases produced by midazolam were modeled as a stimulation
      sedation model that consisted of two opposing effect-link sigmoidal Emax
      functions. The stimulation-sedation model suggested that midazolam possesses both
      stimulatory and sedative effects in a continuous but sequential fashion, and
      hypothesizes the coexistence of stimulation and sedation components for
      midazolam; this model may help delineate possible mechanisms for rebound side
      effects and of tolerance in humans. The reinforcement rate was, then, an index
      for evaluating the deficit in timing performance.

PMID- 9652353
TI  - Na+ channel block prevents the ischemia-induced release of norepinephrine from
      spinal cord slices.
AB  - The principal finding of the present study with rat spinal cord slices was the
      novel demonstration of the [Ca2+]o-independent effect of ischemia on
      norepinephrine release and its antagonism by tetrodotoxin and low temperature (10
      degrees C). Our finding that tetrodotoxin antagonized the effects of glucose
      deprivation on norepinephrine release in a [Ca2+]o-independent way suggests that
      Na+ channel block alone, i.e., the prevention of Na+ accumulation, may account
      for the protective action. Low temperature completely prevented the effect of
      ischemia on norepinephrine release but did not change the release associated with
      axonal activity. This finding is in good agreement with the observation that
      small changes in brain temperature critically determine the extent of neuronal
      injury from ischemia and suggests that both [Ca2+]o-independent release and cell
      injury are associated with the norepinephrine membrane carrier. It is suggested,
      therefore, that drugs able to attenuate the increase in [Na+]i during ischemia
      may be useful agents to protect against ischemic damage if given before the
      insult.

PMID- 9652354
TI  - Temporal dependent neuroprotection with propentofylline (HWA 285) in a temporary
      focal ischemia model.
AB  - Propentofylline (HWA 285, 3-methyl-1-(5-oxo-hexyl)-7-propylxanthine) is an
      adenosine uptake and phosphodiesterase inhibitor that has been shown to be
      neuroprotective in both global and permanent focal ischemia animal models.
      However, to date, the efficacy of propentofylline has never been examined in an
      animal model of temporary focal ischemia or the 'therapeutic window'
      systematically examined in a focal ischemia model. The present experiments were
      designed to investigate these. Temporary (3 h) middle cerebral artery occlusion
      was accomplished by the monofilament method. Infarct volumes were determined at
      24 h from 2,3,5-triphenyltetrazolieum chloride (TTC) stained coronal slices.
      Animals were dosed with vehicle or propentofylline at 3 mg/kg bolus and/or a 6
      mg/kg per h infusion (24 h infusion) at 30 min, 1 h or 3 h post ischemia onset.
      Physiological monitoring on a subset of animals indicated no changes in mean
      arterial pressure, blood gases, blood pH, and glucose levels with either ischemia
      or drug treatment. Propentofylline treatment resulted in a statistically
      significant decrease in infarct volume when an infusion dose of 6 mg/kg per h was
      initiated at 30 min or when a bolus of 3 mg/kg plus an infusion dose was
      initiated at 1 h but not 3 h post ischemia. Therefore, propentofylline is
      neuroprotective in a model of temporary focal ischemia. This suggests that
      combination therapy with propentofylline might lead to clinical improvement
      beyond that which would occur with thrombolytics alone. The apparent short window
      of opportunity for effective dosing is consistent with the proposed mechanism of
      action for propentofylline.

PMID- 9652355
TI  - The effect of the adrenocorticotropin-(4-9) analogue, ORG 2766, and of
      dizolcipine (MK-801) on infarct volume in rat brain.
AB  - The purpose of this study was to evaluate whether the synthetic
      adrenocorticotropin-(4-9) (ACTH-(4-9)) analogue ORG 2766, HMet(O2)-Glu-His-Phe-D
      Lys-Phe-OH, which has been shown to have beneficial effects on both the recovery
      from experimentally induced lesions of the central nervous system and peripheral
      nerve degeneration, has a protective effect on focal ischemic neuronal damage.
      The NMDA receptor antagonist dizolcipine (MK-801), a very potent neuroprotective
      drug, was used as positive reference compound. Isoflurane-anesthetized rats had
      the middle cerebral artery occluded using either an intravasal or an extravasal
      technique, because pilot experiments had shown differences in the severity of
      ischemia for the two middle cerebral artery occlusion techniques. MK-801, 500
      microg kg(-1) min(-1), or saline was administered i.v. 30 min after occlusion of
      the middle cerebral artery. In the ACTH-(4-9) analogue/saline group, 10 and 150
      microg/kg of the analogue, or saline was injected s.c. both directly after and 24
      h after occlusion. The ACTH-(4-9) analogue treatment had no effect on the
      infarction volume in either model of middle cerebral artery occlusion, whereas MK
      801 caused a significant reduction in the volume of cortical infarction in both
      models. We conclude that, although ORG 2766 is known to enhance the recovery from
      experimentally induced lesions of the central nervous system through a
      neurotrophic action and has proven to have significant beneficial effects on
      peripheral nerve regeneration, it did not prevent ischemic neuronal damage after
      intravasal or extravasal middle cerebral artery occlusion in rats. The results
      with MK-801, which caused significant reductions in the volume of cortical
      infarction in both models of middle cerebral artery occlusion, with clearly the
      largest reduction in the intravasal middle cerebral artery occlusion model, again
      indicate that there are differences in the severity of the cerebral ischemia
      which the two models produce in the rat brain.

PMID- 9652356
TI  - Modulatory effect of bradykinin on noradrenaline release in isolated atria from
      normal and B2 knockout transgenic mice.
AB  - The modulatory effect of bradykinin on electrically-induced noradrenaline release
      was assessed in isolated atria from normal and B2 knockout transgenic mice
      preincubated with [3H]noradrenaline. Concentrations of 1, 3 and 10 nM of
      bradykinin did not significantly alter the outflow of radioactivity whereas
      higher concentrations of bradykinin (30 and 100 nM) enhanced it. The facilitatory
      effect of 30 nM bradykinin was inhibited by a selective bradykinin B2 receptor
      antagonist. Hoe 140 (D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]bradykinin, 30 nM), and by a
      protein kinase C inhibitor, bisindolylmaleimide (1 microM). The co-administration
      of bradykinin (1 to 100 nM) with either [Leu8]des-Arg9-bradykinin (100 nM),
      AcLys[DbetaNal7,Ile8]des-Arg9-bradykinin (30 nM) (bradykinin B1 receptor
      antagonists) or diclofenac (1 microM) (a cyclooxygenase inhibitor), shifted the
      facilitatory effect of bradykinin to lower concentrations. The facilitatory
      effect of bradykinin also was enhanced by enalaprilat (1 microM) and mergetpa (1
      microM), inhibitors of angiotensin-converting enzyme (kininase II) and kininase
      I, respectively. In contrast, selective bradykinin B1 receptor agonists, des-Arg9
      bradykinin (1 to 100 nM) and Sar[D-Phe8]des-Arg7-bradykinin (1 to 100 nM), did
      not significantly affect the stimulation-induced outflow of radioactivity.
      Neither bradykinin (100 nM) nor des-Arg9-bradykinin (100 nM) had any modulatory
      effect in B2 knockout transgenic mice. These findings suggest that the
      facilitatory effect of bradykinin on noradrenaline release in the mouse atria is
      mediated exclusively by presynaptic bradykinin B2 receptors which are linked to
      protein kinase C. The greater release of noradrenaline with bradykinin under
      inhibition of prostaglandins production and kininases I and II activity might be
      of importance in pharmacotherapies.

PMID- 9652357
TI  - Differential effects of 5-HT1B/1D receptor antagonists in dorsal and median raphe
      innervated brain regions.
AB  - The effect of SB-224289 (2,3,6.7-tetrahydro-1'-methyl-5-?2'-methyl-4'-[(5-methyl
      1,2,4-oxadiazol e-3-yl)biphenyl-4-yl]carbonyl?Furo[2,3-F]-indole-3-spiro-4'
      piperidine oxalate) (4 mg/kg i.p., 5-HT1B receptor antagonist), GR 127935 (N-[4
      methoxy-3-(4-methyl-1-piperizinyl)phenyl]-2'-methyl-4'-(5-me thyl-1,2,4
      oxadiazole-3-yl)[1,1'-biphenyl]-carboxamide) (0.3 mg/kg i.p., 5-HT1B/1D receptor
      antagonist), and paroxetine (10 mg/kg p.o.) were investigated on extracellular 5
      hydroxytryptamine (5-HT) levels in the frontal cortex, striatum and dentate gyrus
      of the freely moving guinea-pig with microdialysis. In the frontal cortex and
      striatum (dorsal raphe innervated areas), GR 127935 evoked a significant decrease
      in extracellular 5-HT, reaching minima of 41+/-12% and 32+/-6% of basal,
      respectively. This decrease may be explained by antagonism of inhibitory 5
      HT1B/1D receptors on raphe cell bodies, leading to a local increase in 5-HT,
      which, in turn, stimulated 5-HT1A receptors to decrease cell firing, and hence 5
      HT release from terminals. In contrast, SB-224289 had no effect on 5-HT levels in
      either region. In the dentate gyrus (median raphe innervated area), GR 127935 and
      SB-224289 significantly increased extracellular 5-HT, reaching maxima of 146+/
      11% and 151+/-19% of basal, respectively. The ability of both compounds to
      increase 5-HT levels in the dentate gyrus suggests a lack of 5-HT1B/1D receptors
      in the median raphe nucleus. Paroxetine produced a small but non-significant
      increase in extracellular 5-HT in the frontal cortex, and a small decrease in the
      dentate gyrus. The lack of effect of paroxetine in terminal areas may be due to
      the limiting effects of cell body 5-HT autoreceptors. In summary, the above data
      demonstrate that 5-HT1B/1D receptor antagonists increase 5-HT levels in the
      dentate gyrus, implying that acute administration of 5-HT1B/1D receptor
      antagonists will achieve a similar effect to chronic selective serotonin re
      uptake inhibitor treatment in median raphe innervated areas. This, in turn,
      suggests that such compounds may be efficacious in the treatment of depression.

PMID- 9652358
TI  - MDMA ('Ecstasy') enhances 5-HT1A receptor density and 8-OH-DPAT-induced
      hypothermia: blockade by drugs preventing 5-hydroxytryptamine depletion.
AB  - One week after a single administration of 3,4-methylenedioxymethamphetamine (MDMA
      HCI, 30 mg/kg i.p.), 5-HT1A receptor density was significantly increased by
      approximately 25-30% in the frontal cortex and hypothalamus of rats. The
      increased density correlated with the potentiation of the hypothermic response to
      the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 1
      mg/kg s.c.). Hypothalamic 5-HT7 receptors, which also bind 8-OH-DPAT, were not
      changed, however, by MDMA. Fluoxetine (5 mg/kg s.c.), ketanserin (5 mg/kg s.c.)
      or haloperidol (2 mg/kg i.p.), given 15 min prior to MDMA, prevented the
      depletion of 5-hydroxytryptamine (5-HT) induced by MDMA and also blocked the
      effects of this neurotoxin on 5-HT1A receptor density and on 8-OH-DPAT-induced
      hypothermia. The protection afforded by drugs against 5-HT loss did not
      correlate, however, with the antagonism of the acute hyperthermic effect of MDMA.
      The present results indicate that drugs able to prevent or to attenuate MDMA
      induced 5-HT loss also prevent the changes in 5-HT1A receptor density as well as
      the enhanced hypothermic response to the 5-HT1A receptor agonist 8-OH-DPAT in
      MDMA-treated rats.

PMID- 9652359
TI  - Modulation of amphetamine-stimulated (transporter mediated) dopamine release in
      vitro by sigma2 receptor agonists and antagonists.
AB  - Some sigma receptor ligands have been shown to bind with low affinity to the
      dopamine transporter and to inhibit [3H]dopamine uptake. It has not previously
      been shown whether any of these compounds influence release of dopamine via
      facilitated exchange diffusion. To further examine the nature of the interaction
      between sigma receptor ligands and the dopamine transporter, the effects of sigma
      receptor ligands on amphetamine-stimulated [3H]dopamine release were examined in
      slices prepared from rat caudate putamen. In the absence of exogenous Ca2+, both
      (+)-pentazocine and (-)-pentazocine potentiated amphetamine-stimulated
      [3H]dopamine release at concentrations consistent with their affinities for
      sigma2 receptors. In contrast, BD737 (1S.2R-(-)-cis-N-?2-(3,4
      dichlorophenyl)ethyl?-N-methyl-2-(1-pyrrolidiny l)cyclohexylamine), a sigma1
      receptor agonist, had no effect on amphetamine-stimulated release. Neither isomer
      of pentazocine alone had any effect on basal [3H]dopamine release under these
      conditions. Three antagonists at sigma receptors, one of which is non-selective
      for subtypes, and two of which are sigma2-selective, all blocked the enhancement
      of stimulated release produced by (+)-pentazocine. Enhancement of stimulated
      release by (-)-pentazocine was similarly blocked by sigma2 receptor antagonists.
      Our data support the contention that it is possible to regulate transporter
      mediated events with drugs that act at a subpopulation of sigma receptors
      pharmacologically identified as the sigma2 subtype.

PMID- 9652360
TI  - Tonic GABA(A) receptor-mediated neurotransmission in the dorsal vagal complex
      regulates intestinal motility in rats.
AB  - Vagal motor outflow from the dorsal vagal complex is important in the regulation
      of intestinal motility. The aim of our study was to test the hypothesis that
      within the dorsal vagal complex, tonic GABA(A)-receptor mediated
      neurotransmission modulates intestinal motility. The GABA(A) receptor antagonist,
      bicuculline (methiodide), was microinjected into the dorsal vagal complex, and
      the effects on small intestinal and colonic motility were investigated. Rats were
      anesthetized and the mean arterial pressure and heart rate were monitored.
      Jejunal and colonic motility were measured manometrically, and motility indices
      were calculated manually. Bicuculline at concentrations of 0.25 or 0.5 mM in 30
      nl was microinjected bilaterally into the dorsal vagal complex through
      stereotaxically placed micropipettes. The injection sites were confirmed
      histologically using the dye Alcian Blue. Bicuculline (0.5 mM) inhibited
      spontaneous jejunal motility by 76.3%, colonic motility by 51.7%, mean arterial
      pressure by 23.3% and heart rate by 27.6%. The lower concentration of bicuculline
      (0.25 mM) showed no inhibitory effects on intestinal motility but decreased mean
      arterial blood pressure by 24.1% and heart rate by 13.6%. Bilateral cervical
      vagotomy attenuated the bicuculline (0.5 mM)-induced inhibition of spontaneous
      jejunal motility, whereas the bicuculline effect on colonic motility was
      unaffected. The results of this study show that GABA(A) receptor-mediated
      neurotransmission in the dorsal vagal complex is involved in autonomic
      integration of motility of the small intestine and colon. Furthermore, our
      results indicate that the dorsal vagal complex regulation of jejunal motility
      involves vagal outflow, whereas vagal pathways do not participate in the
      bicuculline-induced inhibition of colonic motility.

PMID- 9652361
TI  - Dissociation of morphine-induced potentiation of turning and striatal dopamine
      release by amphetamine in the nigrally-lesioned rat.
AB  - Morphine has been reported to increase extracellular levels of dopamine in the
      brain of intact rats and to potentiate turning induced by amphetamine in nigrally
      lesioned rats. The present study tested the hypothesis that there is a causal
      relationship between these two effects of morphine. We tested morphine alone,
      amphetamine alone, and the combination in separate groups of nigrally-lesioned
      rats for effects on turning and, by microdialysis, on extracellular dopamine
      levels. Morphine (3.0 or 10 mg/kg) did not produce significant turning but
      amphetamine (1.0 mg/kg) did. The lower dose, but not the higher dose, of morphine
      potentiated amphetamine-induced turning. Amphetamine, but not morphine, produced
      increases in extracellular dopamine levels. In contrast to what occurred with
      turning, 10 mg/kg but not 3.0 mg/kg morphine potentiated amphetamine-induced
      increases in extracellular dopamine levels. These results show that the
      potentiation of amphetamine-induced turning by morphine in nigrally-lesioned rats
      is not due to the potentiation of dopamine release in the intact striatum.

PMID- 9652362
TI  - Differential regional antagonism of 8-OH-DPAT-induced decrease in serotonin
      synthesis by two 5-HT1A receptor antagonists.
AB  - The effects of two 5-HT1A receptor antagonists, (R)-3-N, N-dicyclobutylamino-8
      fluoro-3,4-dihydro-2 H-1-benzopyran-5-carboxamide hydrogen (2 R,3 R)-tartrate
      monohydrate (NAD-299) and N-(2-(1-(2-methoxyphenyl)-piperazinyl))ethyl)-N-(2
      pyridinyl) cyclohexanecarboxamide trihydrochloride (WAY-100635) on the decrease
      in 5-hydroxytryptophan (5-HTP) accumulation evoked by (RS)-2-dipropylamino-8
      hydroxy-1,2,3,4-tetrahydronaphthalene (8-OH-DPAT) in rats treated with the
      decarboxylase inhibitor, 3-hydroxyphenylhydrazine (NSD 1015) were studied in four
      rat brain regions: hippocampus, hypothalamus, striatum and frontal cortex. Dose
      response studies revealed differential effects of both antagonists in the areas
      examined. Both antagonists were significantly more potent in antagonising the
      effect of 0.30 and 0.76 micromol/kg s.c. 8-OH-DPAT in hippocampus than in
      hypothalamus, striatum and frontal cortex in mentioned order. This order of
      potency was the opposite to that found for 8-OH-DPAT in decreasing the 5-HTP
      accumulation. Since previous studies by others have indicated that the reserve of
      somatodendritic 5-HT1A receptors is greater in dorsal raphe nucleus innervating
      frontal cortex and striatum than in median raphe nucleus which mainly innervates
      hippocampus, the observed different regional potency of the two 5-HT1A receptor
      antagonists may be explained by this difference in the 5-HT1A receptor reserve.

PMID- 9652363
TI  - The role of P-selectin, sialyl Lewis X and sulfatide in myocardial ischemia and
      reperfusion injury.
AB  - The role of P-selectin and the ligands of selectins such as sialyl Lewis X and
      sulfatide was studied in a myocardial ischemia and reperfusion injury model.
      Anesthetized rabbits underwent the occlusion of coronary artery (30 min) followed
      by reperfusion (5 h). The inhibitory effect on myocardial ischemia and
      reperfusion injury was examined with infarct size normalized by area-at-risk.
      Intravenous administration of an anti-P-selectin monoclonal antibody, PB1.3 (2
      mg/kg), reduced infarct size by 38%. Similarly, the administration of sialyl
      Lewis X-oligosaccharide (10 mg/kg) reduced infarct size by 53% significantly.
      Finally, the infarct size was significantly reduced bv 39% in sulfatide-treated
      group (10 mg/kg). These results suggest that P-selectin plays an important role
      in myocardial ischemia and reperfusion injury and that the ligands of selectins,
      such as sialyl Lewis X-oligosaccharide and sulfatide, have cardioprotective
      effect on myocardial ischemia and reperfusion injury.

PMID- 9652364
TI  - Muscarinic M1 receptor activation reduces maximum upstroke velocity of action
      potential in mouse right atria.
AB  - We investigated whether acetylcholine affects cardiac action potentials through
      the muscarinic M1 in addition to M2 receptors in spontaneously beating mouse
      isolated right atria. A conventional glass microelectrode technique was used for
      the purpose. Acetylcholine (3-10 microM) reduced the maximum upstroke velocity of
      the action potentials (Vmax), followed by an increase. It shortened action
      potential duration at 90% repolarization, hyperpolarized the resting membrane and
      decreased the rate of beating. Atropine (3-100 nM) concentration dependently
      antagonized these effects of acetylcholine. Pirenzepine (10 and 30 nM), a
      selective muscarinic M1 receptor antagonist, antagonized acetylcholine (5 microM)
      induced reduction of Vmax without affecting other effects of acetylcholine. In
      addition, pirenzepine (30 nM) induced an immediate and linear acceleration of the
      VmaX reduced by acetylcholine. In contrast, AF-DX 116 (11(?2-[(diethylamino)
      methyl]-1-piperidyl?acetyl)-5,11-dihydro-6 H-pyridol[2,3-b][1,4]benzodiazepine-6
      one base, 30-300 nM), a selective muscarinic M2 receptor antagonist, failed to
      antagonize acetylcholine-induced reduction of Vmax, but abolished its increase.
      It antagonized the shortening of action potential duration, membrane
      hyperpolarization and decreased the beating rate. McN-A-343 (4-(m-chlorophenyl
      carbamoyloxy)-2-butynyltrimethylammonium chloride, 100 and 300 microM), a
      muscarinic M1 receptor agonist, reduced Vmax and prolonged action potential
      duration, while oxotremorine (100-300 nM), a muscarinic M2 receptor agonist,
      evoked reverse effects. These results suggest that acetylcholine exerts a mixed
      effect on Vmax, consisting of a reduction and a facilitation, possibly mediated
      by concurrent activation of muscarinic M1 and M2 receptors, respectively, in
      isolated right atria of mice.

PMID- 9652365
TI  - Effects of 2,5-di-t-butyl-1,4-benzohydroquinone (BHQ) on rat aorta smooth muscle.
AB  - To characterise the pharmacological activity of 2,5-di-t-butyl-1,4
      benzohydroquinone (BHQ) on vascular smooth muscle, the different effects of BHQ
      on rat aorta were investigated under several experimental conditions. In aortic
      rings at rest or depolarised with 80 mM K+ in the presence of 1 microM
      nifedipine, BHQ evoked a slow tonic contraction which was antagonised by 1 mM
      Ni2+. Depolarised rings contracted in response to addition of 1 mM Ca2+, with an
      EC50 value of 32.4+/-1.0 mM for K+. At 20 mM K+, Ca2+-induced contraction was
      enhanced by BHQ. This effect was antagonised by 1 mM Ni2+, but not by 1 microM
      nifedipine. By contrast, at 40, 80 and 128 mM K+, BHQ antagonised Ca2+-induced
      contraction. This effect was partially reversed by 1 microM methyl-1,4-dihydro
      2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyri dine-5-carboxylate (Bay K
      8644) or by increasing extracellular Ca2+ concentration. In the presence of
      nifedipine and Ni2+, depolarised rings (80 mM K+) contracted in response to
      addition of 1 microM phenylephrine; this response was fast and then slowly
      decreased. When the preparations were preincubated with BHQ, the phenylephrine
      induced contraction was transient and antagonised in a concentration-dependent
      manner by BHQ. These results indicate that the myotonic effect of BHQ on rat
      aortic rings depends on activation of Ca2+ influx via a Ni2+-sensitive pathway,
      whereas its myolytic activity is due either to antagonism of Ca2+ entry via L
      type Ca2+ channels or depletion of intracellular Ca2+ stores.

PMID- 9652366
TI  - Comparison of the antiarrhythmic and the proarrhythmic effect of almokalant in
      anaesthetised rabbits.
AB  - In this study the antiarrhythmic and the proarrhythmic activities of almokalant,
      a selective class III antiarrhythmic agent, were compared. The antiarrhythmic
      effect of the drug was tested in pentobarbital-anaesthetised rabbits. Arrhythmia
      was evoked by occluding and releasing the left circumflex coronary artery.
      Almokalant in a dose of 250 nmol/kg i.v., significantly decreased the incidence
      of reperfusion induced ventricular fibrillation (21% vs. 75% in the control
      group) and increased the proportion of surviving animals during reperfusion (86%
      vs. 42%). The proarrhythmic effect of almokalant was examined during alpha1
      adrenoceptor stimulation in chloralose-anaesthetised rabbits. Almokalant (75
      nmol/kg per min) triggered torsade de pointes arrhythmias in 8 animals out of 11.
      The dose of almokalant (mean+/-S.E.M.) required to produce this effect was 1181+/
      519 nmol/kg. It is concluded that, although almokalant is an effective
      antiarrhythmic agent against ischaemia-reperfusion induced arrhythmias, it has
      marked proarrhythmic activity during alpha1-adrenoceptor stimulation.

PMID- 9652367
TI  - Effects of K+ channel inhibitors on the basal tone and KCl- or methacholine
      induced contraction of mouse trachea.
AB  - The present study examined the effects of K+ channel inhibitors on the basal tone
      and on KCl- or methacholine-induced contraction of the mouse-isolated trachea.
      Glibenclamide and iberiotoxin, procaine, quinine and tetraethylammonium did not
      induce any contraction of the indomethacin-treated mouse trachea. 4-Aminopyridine
      induced concentration-dependent contraction. This action of 4-aminopyridine was
      abolished by atropine and reduced by tetrodotoxin and nifedipine. Glibenclamide
      failed to modify KCl- or methacholine-induced contraction. Iberiotoxin and 4
      aminopyridine potentiated KCl- and methacholine-induced contractions. Nifedipine,
      procaine, quinine and tetraethylammonium inhibited KCl- and methacholine-induced
      contractions. These data suggest that the closure of large Ca2+-dependent K+
      channels can potentiate KCI- and methacholine-induced contraction. The effects of
      4-aminopyridine on the mouse trachea reflect chiefly activation of muscarinic
      receptors. Procaine, quinine and tetraethylammonium inhibit depolarization
      induced and receptor-mediated contractions of the mouse-isolated trachea.

PMID- 9652368
TI  - WAY-100635 inhibits 8-OH-DPAT-stimulated oxytocin, ACTH and corticosterone, but
      not prolactin secretion.
AB  - Previous studies suggest that the 5-HT1A receptor agonist 8-hydroxy-2-(di-n
      propylamino) tetralin (8-OH-DPAT) increases the secretion of oxytocin,
      adrenocorticotropic hormone (ACTH), corticosterone and prolactin but not renin.
      However, the lack of selective 5-HT1A receptor antagonists made it difficult to
      confirm that 5-HT1A receptors mediate the neuroendocrine responses to 8-OH-DPAT.
      This study investigated the effects of increasing doses of a selective 5-HT1A
      receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2
      pyridinyl) cyclohexanecarboxamide (WAY-100635) on neuroendocrine responses
      induced by the 5-HT1A receptor agonist 8-OH-DPAT in adult male rats. 8-OH-DPAT,
      500 microg/kg s.c., increased plasma levels of oxytocin (to 970% above basal
      levels); ACTH (to 1622% above basal levels), corticosterone (to 458% above basal
      levels) and prolactin (to 313% above basal levels), but not renin. The lowest
      dose of WAY-100635 (0.1 mg/kg s.c.) significantly inhibited the 8-OH-DPAT-induced
      increase in plasma oxytocin but not ACTH or corticosterone levels. At a dose of 1
      mg/kg (s.c.), WAY-100635 completely blocked the oxytocin and ACTH responses and
      maximally inhibited the corticosterone response to 8-OH-DPAT, although
      corticosterone levels were still above basal. In contrast, the increase in
      prolactin secretion, induced by 8-OH-DPAT was not inhibited by any dose of WAY
      100635. At the highest dose of WAY-100635 (10 mg/kg, s.c.), basal prolactin
      levels were markedly elevated (1550%) and administration of 8-OH-DPAT
      significantly elevated plasma renin concentration. Taken together, these data
      indicate that: (1) 8-OH-DPAT stimulates oxytocin, ACTH, and corticosterone but
      not prolactin secretion via activation of 5-HT1A receptors and (2) blockade of 5
      HT1A receptors may unmask 8-OH-DPAT simulation of renin secretion via non-5-HT1A
      receptor mechanisms.

PMID- 9652369
TI  - The involvement of nitric oxide in stress-impaired testicular steroidogenesis.
AB  - The participation of the nitric oxide (NO) pathway in downregulation of
      testicular steroidogenesis in normal and stressed rats was investigated both in
      vivo and in vitro. In Leydig cells from normal animals, isosorbide dinitrate, an
      NO donor, decreased the human chorionic gonadotropin (CG)-stimulated and
      progesterone-derived androgen production. Also, the intratesticular injection of
      a precursor of NO, arginine (10 mg/testis), transiently decreased serum androgen
      levels and inhibited human CG-stimulated androgen production in acute testicular
      cultures. These effects were eliminated in rats cotreated with Nomega-nitro-L
      arginine methyl ester (L-NAME) (2 X 600 microg/each testis). Acute immobilization
      stress (2 h) decreased serum androgen levels and inhibited human CG-stimulated
      androgen production in vitro. These effects were accompanied by a significant
      increase in nitrite, a stable oxidation product of NO, in testicular cultures.
      Bilateral intratesticular injection of L-NAME prevented the stress-induced
      decrease of human CG-stimulated androgen production, and significantly reduced
      the nitrite levels. These results implicate NO in normal and stress-impaired
      testicular steroidogenesis.

PMID- 9652370
TI  - L-arginine and NG-nitro-L-arginine methyl ester cause macromolecule extravasation
      in the microcirculation of awake hamsters.
AB  - We investigated the effects of L-arginine and NG-nitro-L-arginine methyl ester (L
      NAME) on macromolecule extravasation in the microcirculation of awake hamsters by
      computer-assisted image analysis of the distribution of FITC (fluorescein
      isothiocyanate)-dextran fluorescence in dorsal fold skin preparations. This
      analysis made it possible to simultaneously study the time course of local (skin)
      and general (all irrigated organs) extravasation in 180-min experiments. Bolus
      injection of 30 or 150 mg/kg (i.v.) L-arginine induced immediate local and
      general macromolecule leakage and delayed venule dilation beginning 1 h later.
      Injection of 20 or 100 mg/kg (i.v.) L-NAME caused rapid venule constriction
      followed by local and general extravasation beginning 45-60 min later. These
      effects of L-arginine and L-NAME were not mimicked by their biologically inactive
      isomers, D-arginine and D-NAME. Simultaneous bolus injection of 20 mg/kg L-NAME
      and 150 mg/kg L-arginine caused no significant change in fluorescence
      distribution or venule diameter. L-arginine effects on macromolecule
      extravasation were mimicked by sodium nitroprusside (10 microg/kg, i.v.) and by 8
      bromo-cGMP (1 mg/kg, i.v.). Sodium nitroprusside was ineffective on venule
      diameter. The effects of both L-arginine and sodium nitroprusside on FITC-dextran
      extravasation were prevented by simultaneous injection (10 microg/kg, i.v.) of
      the specific inhibitor of the soluble guanylate cyclase, 1H-[1,2,4]oxadiazolo[4,3
      a]quinoxalin-1-one (ODQ). This dose of ODQ mimicked the effects of L-NAME on
      macromolecule extravasation and venule diameter. Taken together, these results
      suggest that activation or inhibition of basal NO synthesis might induce
      macromolecule leakage in the microcirculation of awake hamsters via temporally
      distinct cGMP-dependent mechanisms.

PMID- 9652371
TI  - Tetracycline inhibits the nitric oxide synthase activity induced by endotoxin in
      cultured murine macrophages.
AB  - Here we investigate the effects of tetracycline base and of a semi-synthetic
      tetracycline derivative, doxycycline, on the induction of inducible nitric oxide
      synthase and, hence, on the production of nitric oxide (NO) by lipopolysaccharide
      in J774 macrophage cultured in vitro. The treatment of J774 line with
      tetracycline base (6.25-250 microM) or doxycycline (5-50 microM) dose-dependently
      decreased the lipopolysaccharide-stimulated (1 microg/ml) inducible NO synthase
      activity and, consequently, nitrite formation. For instance, the inhibition was
      70% for tetracycline base at 250 microM and 68% for doxycycline at 50 microM. The
      inhibitory effect of tetracyclines was due neither to a reduction in the
      viability of the cells, studied as colorimetric 3-[4,5-dimethylthiazol-2yl]-2,5
      diphenyltetrazolium bromide (MTT) reduction assay, nor to an indiscriminate
      inhibition of total protein synthesis, but to a specific decrease in inducible NO
      synthase protein content in the cells, as attested by the significant reduction
      of the expression of inducible NO synthase, assayed by sodium-dodecyl sulphate
      polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot. However, no
      effect of tetracyclines on inducible NO synthase mRNA accumulation could be
      demonstrated in lipopolysaccharide-stimulated macrophage line, suggesting that
      the inhibitory effect of tetracyclines on NO synthesis involves post
      transcriptional events. The reduction in lipopolysaccharide-stimulated nitrite
      accumulation produced by tetracyclines was significantly less when they were
      applied 6 h after lipopolysaccharide and absent 12 h after lipopolysaccharide,
      indicating that tetracyclines modify an early event in inducible NO synthase
      activation operating after mRNA transcription. The findings presented in this
      study indicate that the modulation of NO synthesis is another possible pathway by
      which tetracyclines may function as anti-inflammatory compounds.

PMID- 9652372
TI  - Cloning, sequencing and functional expression of a guinea pig lung bradykinin B2
      receptor.
AB  - Kinin receptors are classified as B1 and B2 based upon agonist and antagonist
      potencies and cloning and expression studies. Using sequences from human and rat
      bradykinin B2 receptors, polymerase chain reaction (PCR) was utilized to isolate
      cDNA from guinea pig lung. The receptor obtained is predicted to have 372 amino
      acids and shares > 80% sequence homology with human, rat, rabbit and mouse B2
      receptors. In competition binding experiments in Chinese hamster ovary (CHO-K1)
      cells in which the guinea pig cDNA was expressed, [3H]bradykinin was displaced by
      kinin receptor ligands with an order of potency consistent with a B2 subtype. In
      CHO cells expressing the guinea pig receptor, bradykinin caused a concentration
      45Ca2+ efflux. A B1 receptor agonist, desArg9-bradykinin, also caused 45Ca2+
      efflux but with a potency several orders of magnitude lower than bradykinin.
      Curiously, several B1 and B2 receptor antagonists induced 45Ca2+ efflux,
      indicating that this receptor may be coupled differently in CHO cells than in
      native tissues.

PMID- 9652373
TI  - Interactions of ligands with active and inactive conformations of the dopamine D2
      receptor.
AB  - The affinities of 19 pharmacologically diverse dopamine D2 receptor ligands were
      determined for the active and inactive conformations of cloned human dopamine D2
      receptors expressed in Ltk cells. The agonist [3H]quinpirole was used to
      selectively label the guanine nucleotide-binding protein-coupled, active receptor
      conformation. The antagonist [3H]raclopride, in the presence of the non
      hydrolysable GTP-analogue Gpp(NH)p and sodium ions and in the absence of
      magnesium ions, was used to label the free inactive receptor conformation. The
      intrinsic activities of the ligands were determined in a forskolin-stimulated
      cyclic AMP assay using the same cells. An excellent correlation was shown between
      the affinity ratios (KR/KRG) of the ligands for the two receptor conformations
      and their intrinsic activity (r=0.96). The ligands included eight structurally
      related and enantiopure 2-aminotetralin derivatives; the enantiomers of 5-hydroxy
      2-(dipropylamino)tetralin, 5-methoxy-2-(dipropylamino)tetralin, 5-fluoro-2
      (dipropylamino)tetralin and 2-(dipropylamino)tetralin. The (S)-enantiomers
      behaved as full agonists in the cyclic AMP assay and displayed a large KR/KRG
      ratio. The (R)-enantiomers were classified as partial agonists and had lower
      ratios. The structure-affinity relationships of these compounds at the active and
      the inactive receptor conformations were analysed separately, and used in
      conjunction with a homology based receptor model of the dopamine D2 receptor.
      This led to proposed binding modes for agonists, antagonists and partial agonists
      in the 2-aminotetralin series. The concepts used in this study should be of value
      in the design of ligands with predetermined affinity and intrinsic activity.

PMID- 9652374
TI  - Inhibition by taurine of the inwardly rectifying K+ current in guinea pig
      ventricular cardiomyocytes.
AB  - Effects of taurine on the inwardly rectifying K+ current (IK1) in isolated guinea
      pig ventricular cardiomyocytes were examined using patch voltage-clamp methods.
      All experiments were performed at 36 degrees C. Taurine (10-20 mM) increased the
      action potential duration, but failed to affect the resting potential. Holding
      potential was maintained at -30 mV. The current was activated with an inwardly
      going rectification, and was completely blocked by Ba2+ (2 mM). Taurine inhibited
      IK1 at - 120 mV by 28.3+/-1.1% (n=6, P < 0.05) at 10 mM and by 36.0+/-2.1% (n=6,
      P < 0.01) at 20 mM. The reversal potential was shifted in the hyperpolarizing
      direction by 3.7+/-0.6 mV (n=6) at 20 mM. In inside-out patch-clamp experiments,
      the amplitude of unitary channels was -2.7+/-0.3 pA (n=21) at -90 mV. Symmetrical
      high-K+ (150 mM) solutions in both bath and pipette were used. The channel
      conductance was 32+/-2 pS (n=9). Taurine did not affect channel conductance, but
      markedly decreased the open probability at - 120 mV of channel by 21.5+/-2.4%
      (n=8, P < 0.01) at 10 mM, and by 56.7+/-3.8% (n=8, P < 0.001) at 20 mM. These
      responses were almost reversible. These results suggest that taurine directly
      modulates the open probability of the inwardly rectifying K+ current, resulting
      in regulation of the functions of heart cells.

PMID- 9652375
TI  - Relationship between cytotoxic drug response patterns and activity of drug efflux
      transporters mediating multidrug resistance.
AB  - Drug activity patterns in 10 human tumor cell lines representing defined
      mechanisms of drug resistance, including cell lines with high expression of P
      glycoprotein and multidrug resistance associated protein (MRP), have previously
      been used for prediction of mechanism of drug action. In the present study, this
      cell line panel was analyzed for cellular accumulation of the fluorescent probe
      calcein/AM [4'5'-bis(N,N-bis (carboxymethyl) aminomethyl) fluorescein
      acetoxymethyl ester] and compared with drug response patterns of 20 standard
      chemotherapeutic drugs. According to degree of correlation with the ability to
      exclude calcein/AM, topoisomerase II inhibitors and tubulin actives were at the
      top of the list although the correlations were of lower magnitude than those
      obtained from the drug response patterns of mechanistically similar drugs. There
      was a significant relationship between the rank-order of drugs based on
      correlation with calcein/AM accumulation and Pgp/MRP mediated drug resistance
      suggesting that compounds being substrates for these pumps were identified. In
      simulated drug response profiles, the impact of Pgp and MRP expressing cell lines
      on the mechanistic prediction was found to be marginal. The results indicate that
      the differential molecular function/expression in the cell line panel may
      identify drugs interacting with specific biochemical pathways. Furthermore, the
      presence of cell lines overexpressing drug efflux mechanisms in the panel do not
      significantly influence the mechanistic predictions.

PMID- 9652377
TI  - Sulpiride, but not haloperidol, up-regulates gamma-hydroxybutyrate receptors in
      vivo and in cultured cells.
AB  - Five days of gamma-hydroxybutyrate (GHB) administration (3 x 500 mg kg(-1) day(
      1) i.p.) to rats resulted in a significant decrease in the density of GHB
      receptors measured in the whole rat brain without modification of their
      corresponding affinity. Similar administration of (-)-sulpiride (2 X 100 mg kg(
      1) day(-1) i.p. for 5 days) induces an up-regulation of GHB receptors without
      change in their dissociation constants (Kd). Haloperidol (2 X 2 mg day(-1) i.p.
      for 5 days) showed no effect. Administered chronically via osmotic minipumps
      directly into the lateral ventricles, (-)-sulpiride (60 microg day(-1) for 7
      days) and GHB (600 microg day(-1) for 7 days) up-regulated and down-regulated rat
      brain GHB receptors, respectively. Finally, in a mouse hybridoma cell line (NCB
      20 cells) expressing GHB receptors, the treatment of these cells with 1 mM GHB,
      100 microM (-)-sulpiride or 1 mM GABA decreases, increases and induces no change,
      respectively, in the density of GHB receptors after 3 days of treatments. These
      results indicate that chronic GHB treatment modifies the expression of its
      receptor and that sulpiride also induces plastic changes in GHB receptors perhaps
      via antagonistic properties.

PMID- 9652376
TI  - Muscarinic cation current and suppression of Ca2+ current in guinea pig ileal
      smooth muscle cells.
AB  - Cationic current (Icat) and inhibition of the voltage-dependent Ca2+ current
      (ICa) evoked by muscarinic receptor activation with carbachol were studied using
      whole-cell patch clamp technique in smooth muscle cells isolated from
      longitudinal muscle of guinea pig small intestine. With low buffering of [Ca2+]i
      (0.1 mM BAPTA [1,2-bis-(2-aminophenoxy)-ethane-N,N, N', N'-tetraacetic acid] in
      pipette solution) Icat and ICa inhibitory responses had a rapid onset to an
      initial peak followed by a sustained phase. The sustained phase of ICa
      suppression was bigger than in the case when [Ca2+]i was clamped to 100 nM, but
      decreased with repeated stimulation. Upon repeated stimulation with 50 microM
      carbachol in cells where [Ca2+]i was clamped to 100 nM and when GTP was absent,
      Icat amplitude decreased strongly and more substantially compared to ICa
      inhibition, but both responses declined only slightly when 1 mM GTP was present
      in the pipette solution. GDP-betaS (1 or 5 mM) in pipette solution or pre
      treatment of cells with pertussis toxin (6 microg/ml, for 4 h or longer) blocked
      Icat more than ICa suppression by carbachol, whereas L-NAME (N-omega-nitro-L
      arginine methyl ester hydrochloride) (100 microM in pipette solution) affected
      neither of them significantly. We conclude that the cationic current and the
      suppression of the voltage-dependent Ca2+ current evoked by muscarinic receptor
      activation are mediated by pertussis toxin-sensitive G-protein(s) but the latter
      response was less sensitive to blockade by GDP-betaS and to GTP deficiency in the
      cell.

PMID- 9652378
TI  - Effect of adenosine receptor agonists on release of the nucleoside analogue
      [3H]formycin B from cultured smooth muscle DDT1 MF-2 cells.
AB  - Adenosine has receptor-mediated effects in a variety of cell types and is
      predominantly formed from ATP by a series of nucleotidase reactions. Adenosine
      formed intracellularly can be released by bidirectional nucleoside transport
      processes to activate cell surface receptors. We examined whether stimulation of
      adenosine receptors has a regulatory effect on transporter-mediated nucleoside
      release. DDT1 MF-2 smooth muscle cells, which possess nitrobenzylthioinosine
      sensitive (ES) transporters as well as both adenosine A1 and A2 receptors, were
      loaded with the metabolically stable nucleoside analogue [3H]formycin B. N6
      cyclohexyladenosine (CHA), a selective adenosine A1 receptor agonist, produced a
      concentration-dependent inhibition of [3H]formycin B release with an IC50 value
      of 2.7 microM. Further investigation revealed CHA interacts directly with
      nucleoside transporters with a Ki value of 3.3 microM. Neither 5'-N
      ethylcarboxamidoadenosine (NECA), a mixed adenosine A1 and A2 receptor agonist,
      nor CGS 21680, a selective adenosine A2A receptor agonist, affected nucleoside
      release. We conclude that release of the nucleoside formycin B from DDT1 MF-2
      cells is not regulated by adenosine A1 or A2 receptor activation.

PMID- 9652379
TI  - U73122 and U73343 inhibit receptor-mediated phospholipase D activation downstream
      of phospholipase C in CHO cells.
AB  - The aminosteroid 1-(6-?[17beta-3-methoxyestra- 1,3,5(10)-trien- 17-yl]
      amino?hexyl)- 1H-pyrrole-2,5-dione (U73122) and its inactive analogue 1-(6
      ?[17beta-3-methoxyestra-1,3,5(10)-trien- 17-yl]-amino?hexyl-2,5-pyrrolidine-dione
      (U73343) are widely used to study the involvement of G protein-coupled 1
      phosphatidylinositol-phosphodiesterase, or phospholipase C, in receptor-mediated
      cell activation. The present work shows that both aminosteroids inhibit
      cholecystokinin-(26-33)-peptide amide (CCK-8)-induced phospholipase D activation
      equipotently in Chinese hamster ovary cells expressing the cholecystokinin-A
      receptor (CHO-CCK(A) cells). In addition, the two aminosteroids virtually
      completely inhibited thapsigargin- and 12-O-tetradecanoylphorbol 13-acetate (TPA)
      induced phospholipase D activation. Since the latter two drugs mimic inositol
      1,4,5-trisphosphate-mediated Ca2+ mobilisation and 1,2-diacylglycerol-mediated
      protein kinase C activation. respectively, this suggests that both U73122 and
      U73343 act downstream of phospholipase C to inhibit receptor-mediated
      phospholipase D activation. U73122, but not U73343. effectively inhibited both
      TPA/Ca2+-stimulated phospholipase D activation and TPA/phosphatidylserine
      stimulated protein kinase C activation in a homogenate of CHO-CCK(A) cells. The
      data presented suggest that U73122 may act at the level of protein kinase C to
      inhibit activation of phospholipase D. The exact site of action of U73343 is
      presently unknown.

PMID- 9652380
TI  - Toxoplasmosis of rats: a review, with considerations of their value as an animal
      model and their possible role in epidemiology.
AB  - We critically review and summarize information on the prevalence of Toxoplasma
      gondii infections in rats, mainly Rattus norvegicus, and their possible role as a
      source of infection for larger carnivores and omnivores. We also review
      information on immunology and natural resistance, contributing to the model value
      of rats in the analysis of human infection. Rats can be successfully infected
      with oocysts (sporozoites), tissue cysts (bradyzoites), and tachyzoites. Even
      adult rats, that are resistant to clinical toxoplasmosis, can be infected orally
      with a few oocysts or tissue cysts. Infections with tachyzoites of the RH strain
      are highly variable. Congenital transmission of T. gondii occurs at a high rate
      when rats are infected during pregnancy. Congenitally infected rats can harbor
      viable T. gondii in the absence of detectable antibodies to T. gondii and rats
      with low antibody titers may harbor few or no organisms. The isolation of viable
      T. gondii by bioassay is the only reliable means to determine persistence of
      chronic T. gondii infection in feral rats. No evidence was found for maintenance
      of T. gondii in rats by vertical transmission in the absence of cats.

PMID- 9652381
TI  - Oocysts of Cryptosporidium from snakes are not infectious to ducklings but retain
      viability after intestinal passage through a refractory host.
AB  - Six 2-week-old Cryptosporidium-free Peking ducklings (Anas platyrhynchos) each
      received 2.0 x 10(6) viable Cryptosporidium serpentis oocysts from 6 naturally
      infected captive snakes. Histological sections of digestive (stomach, jejunum,
      ileum, cloaca, and cecum) and respiratory tract tissues (larynx, trachea, and
      lungs) did not contain life-cycle stages of Cryptosporidium in any of the
      inoculated ducklings. Because ducklings were refractory to infection, C.
      serpentis transmission via a diet of Peking ducklings is improbable. Viable (per
      in vitro excystation assay) inoculum-derived oocysts were detected in duckling
      feces up to 7 days post-inoculation (PI); the number of intact oocysts excreted
      during the first 2 days PI was significantly higher than for the remaining 5 days
      PI (P < 0.01). The dynamics of oocyst shedding showed that overall the birds
      released a significantly higher number of intact oocysts than oocyst shells (P <
      0.01). Retention of the viability of C. serpentis oocysts following intestinal
      passage through a refractory avian species may have epizootiological
      implications. Under certain circumstances such as after the ingestion of C.
      serpentis-infected prey, herpetivorous birds may disseminate C. serpentis oocysts
      in the environment.

PMID- 9652382
TI  - Immunization against East Coast Fever in field cattle with low infectivity
      Theileria parva stabilate--preliminary assessment.
AB  - Two Theileria parva sporozoite stabilates stored at -196 degrees C, then at -70
      degrees C for six weeks (stabilate 1) and more than six months (stabilate 2) were
      inoculated into four eight-month old male calves, 1 and 2 (stabilate 1), and 3
      and 4 (stabilate 2). Calves 1 and 2 developed pyrexia, enlargement of lymph
      nodes, and the former died of East Coast Fever. Calves 3 and 4 showed slight
      enlargement of lymph nodes without fever. Lymph node smears from all calves (from
      day 10 to 20 post-inoculation) showed lymphoblasts, phagocytic macrophages, and
      schizonts. Piroplasms were detected in erythrocytes in blood smears from calves 1
      and 2 but not in calves 3 and 4. Calves 2, 3 and 4 recovered without any
      treatment while calf 1 died of East Coast Fever on day 20. Serum samples from
      recovered calves taken on day 30 of the experiment were positive for antischizont
      antibodies to T. parva at 1:640 dilution, but pre-inoculation serum samples were
      negative. Stabilate 2 was used to immunize 64 Boran, Friesian, Ayrshire and
      crosses with Zebu cattle in four herds with 25% reduction of oxytetracycline
      dose. All the animals except one calf recovered without any severe reactions. The
      latter died of disease other than ECF after the monitoring period was over (day
      24). Day 30 post-inoculation serum samples were positive for T. parva
      antischizont antibodies. A follow-up of the remaining animals for over one year
      revealed no further ECF incidences in these herds. This experiment shows the loss
      of infectivity of the vaccine stored at temperatures higher than -196 degrees C.
      dependent on the duration. However, despite the lack of clinical signs in calves
      3 and 4, there was cellular response and antibody production, and the stabilate
      for vaccine against East Coast fever can thus be stored prior to use at higher
      than -196 degrees C and still maintain capability to produce antibodies in field
      cattle, eliminating the use of oxytetracycline and monitoring. The vaccine will
      be cheaper and easier to use and the requirement for liquid nitrogen in the field
      reduced and the scale of application of the vaccine widened.

PMID- 9652383
TI  - Hypobiosis of Haemonchus contortus in natural infections of sheep and goats in a
      semi-arid area of Kenya.
AB  - A total of 42 lambs, 42 kids, 21 ewes and 21 does were necropsied during an
      investigation of the epidemiology of Haemonchus contortus infection of sheep (Red
      Maasai) and goats (Small East African Goat) in a semi-arid area of Kenya.
      Availability and establishment of the infective stages were monitored by the
      necropsy of 21 tracer lambs and 21 tracer kids. Prevalence of H. contortus was
      over 90% in both sheep and goats and this species contributed to about 80% of the
      total worm burden. Only about 10% of the hypobiotic larvae were recovered from
      the mucosal digest whereas about 90% were recovered from the abomasal contents
      and washings, thereby suggesting that hypobiotic larvae may be loosely attached
      to the abomasal mucosa from which they may be dislodged during the processing of
      the abomasa for examination. Throughout the study, both adult worms and
      hypobiotic larvae were found in proportions that varied with seasons.
      Statistically, a higher proportion of hypobiotic larvae was found during the dry
      months than during the wet months, an indication that hypobiosis was an important
      feature in the survival of H. contortus during the dry months. Negligible worm
      burdens were acquired by the tracers during the short rains, suggesting that few
      H. contortus larvae survived on pasture in this season. The effectiveness of
      strategic control using ivermectin varied according to the timing in relation to
      the wet season. Treatment did not influence the seasonal pattern of hypobiosis
      but the treatment administered before the onset of the rains significantly
      reduced the numbers of both hypobiotic larvae and the adult worms. Treatment
      during the rains conferred a temporary relief of adult worm burden but had no
      impact on hypobiotic larvae.

PMID- 9652384
TI  - Breed-associated resistance to tick infestation in Bos indicus and their crosses
      with Bos taurus.
AB  - The relative resistance to tick infestation of zebu (Bos indicus) in comparison
      to crossbred (B. indicus x B. taurus) cattle was investigated. B. indicus breeds,
      all belonging to Tanganyika shorthorn zebu were Meru, Mbullu and Iringa red.
      Crossbreds were Meru x Friesian and Iringa red x Friesian. Parameters to
      distinguish between 'tick resistant' and 'tick susceptible' cattle were tick
      counts on naturally exposed animals, serum complement levels and delayed skin
      hypersensitivity response to phytohaemagglutinin. Results have shown that pure
      zebu cattle are less infested with ticks when compared to zebu-taurine crosses
      under identical field conditions. Zebu cattle also had significantly higher serum
      complement level than crossbred cattle. While serum complement and tick burden
      were negatively associated (r = -0.27, P < 0.001), the cutaneous response to
      phytohaemagglutinin did not vary with tick infestation. The influence of cattle
      breed on tick infestation and serum complement level is demonstrated.

PMID- 9652385
TI  - Failure of buparvaquone (Butalex) in the treatment of canine visceral
      leishmaniosis.
AB  - Buparvaquone (Butalex), a therapeutic for theileriosis, has been shown to have
      anti-leishmanial activity in vitro. Seven dogs with symptomatic,
      parasitologically positive, canine visceral leishmaniosis were treated with
      Butalex at 5 mg kg(-1) body weight using four doses over 12 days. Two animals
      showed minor clinical improvement (growth of healthy hair) but all remained
      parasitologically positive and disease progression was not halted.

PMID- 9652386
TI  - Protein translocation into the endoplasmic reticulum (ER)--two similar routes
      with different modes.
AB  - Protein translocation into the endoplasmic reticulum (ER) occurs
      cotranslationally with the ribosome tightly bound at the membrane, or post
      translationally. Transport of polypeptides is performed by an elaborate structure
      in the ER membrane consisting of numerous proteins. Both pathways have been
      reconstituted in vitro using proteoliposomes that contain purified components.
      Primary structures of these key components have been identified and recent
      electron microscopic data provide a first impression of the tertiary structure of
      the translocation apparatus. However, the precise function of most subunits of
      the translocation apparatus is still a mystery and little is known about
      structural changes in the translocation site during a transport cycle.

PMID- 9652387
TI  - Secretion of tetrain, a Tetrahymena cysteine protease, as a mature enzyme and its
      identification as a member of the cathepsin L subfamily.
AB  - A protease in the culture medium of Tetrahymena pyriformis was purified to
      homogeneity. The purified protease had an apparent molecular mass of 28 kDa on
      SDS/PAGE. The amino acid sequences of the N-terminal and internal peptides of the
      protease showed complete identity with those of tetrain, an enzyme previously
      reported as a Tetrahymena cysteine protease but not characterized in detail. Two
      overlapping cDNA clones for tetrain were sequenced, and the nucleotide sequence
      predicts that these clones encode a 330-amino acid protein composed of a 16
      residue N-terminal signal sequence followed by a 103-residue propeptide and a 211
      residue mature protease. The primary structure and enzymatic properties support
      the conclusion that tetrain belongs to the cathepsin L subfamily. Immunoblotting
      analyses showed that mature tetrain was found exclusively in the culture medium.
      Immunofluorescence microscopy demonstrated that tetrain was concentrated in or
      around the food vacuoles of cells in the late logarithmic phase, but the staining
      of food vacuoles was not obvious in the stationary phase. These results suggest
      that tetrain is synthesized at the logarithmic phase and is secreted into the
      culture medium as a mature form.

PMID- 9652388
TI  - The Ulip family phosphoproteins--common and specific properties.
AB  - The search for intracellular phosphoproteins implicated in the regulation of
      neuronal differentiation led to the identification of Ulip1, a mammalian protein
      related to the Caenorhabditis elegans unc-33 gene product [Byk, T., Dobransky,
      T., Cifuentes-Diaz, C. & Sobel, A. (1996) J. Neurosc. 16, 688-701]. The
      expression level and phosphorylation pattern of Ulip1 were shown to be strongly
      regulated during development and neuronal differentiation. We have isolated three
      additional complete coding sequences for members of the Ulip family in the mouse,
      Ulips 2-4, all preferentially expressed in the nervous system. Furthermore, two
      Ulip sequences, Ulips A and Ulips B, could be identified in C. elegans. The Ulip
      family is highly conserved throughout evolution (more than 96 % for Ulips 1-3 and
      92.5 % for Ulip4 between mouse and human) and the various members of the family
      within a single species display about 75% similarity. Sequence comparisons
      further reveal several highly similar domains and subdomains, including a 32
      amino-acid region highly conserved from a bacterial hydantoinase to human Ulips.
      Two-dimensional immunoblot analysis of in vitro translated Ulips 1-4 demonstrates
      the existence, for each Ulip protein, of several, most probably differentially
      phosphorylated forms, in agreement with the presence of conserved phosphorylation
      consensus sites within their sequences. The expression of Ulips 1-4 mRNAs is
      differentially regulated during development and nerve-growth-factor-induced
      neuronal differentiation of PC12 cells. Our results indicate a differential,
      possibly complementary role of phosphoproteins of the highly conserved Ulip
      family in the control of neuronal differentiation, in relation with the
      development and plasticity of the nervous system.

PMID- 9652389
TI  - Contribution to first-pass metabolism of ethanol and inhibition by ethanol for
      retinol oxidation in human alcohol dehydrogenase family--implications for
      etiology of fetal alcohol syndrome and alcohol-related diseases.
AB  - The alcohol dehydrogenase (ADH) family is involved in the metabolism of both
      ethanol and retinoids. To quantitatively assess the potential contributions to
      first-pass metabolism of ethanol and the ethanol interference with retinoid
      homeostasis, saturation kinetics for ethanol oxidation as well as inhibition
      kinetics by ethanol for all-trans-retinol oxidation of human class I alpha alpha,
      beta1beta1, beta2beta2, gamma1gamma1, class II pi pi, class III chi chi, and
      class IV mu mu were evaluated and compared. Class I and class II ADHs exhibited
      substrate inhibition with inhibition constants ranging over 250-720 mM (except
      gamma1gamma1) ethanol. Class IV ADH displayed no appreciable inhibition up to 1 M
      ethanol. Activity of the class III enzyme (190 nM subunit) was undetectable at
      250 mM ethanol. The kinetic simulations indicate that the hepatic pi pi and the
      gastric mu mu can most effectively contribute to first-pass metabolism of
      alcohol. The Michaelis constant (Km), turnover number (k(cat)), and catalytic
      efficiency (k(cat)/Km) for retinol oxidation relative to that for ethanol
      oxidation in class I, class II, and class IV ADHs ranged over 0.00022-1.3, 0.071
      0.48, and 0.24-650, respectively. Ethanol was a competitive inhibitor against
      retinol for class I, II, and IV ADHs with apparent inhibition constants ranging
      over 0.037-11 mM, indicating that retinoic acid synthesis through the ADH
      pathways can be tremendously blocked during social/heavy drinking. These findings
      support the notion that first-pass metabolism of alcohol may occur mainly in the
      liver through class II pi pi and that cellular retinoid signaling may be
      perturbed by ethanol via ADH pathways.

PMID- 9652390
TI  - The defense-related rice gene Pir7b encodes an alpha/beta hydrolase fold protein
      exhibiting esterase activity towards naphthol AS-esters.
AB  - Acquired resistance of rice to Pyricularia oryzae, the causing agent of rice
      blast, can be induced by inoculation with the non-host pathogen Pseudomonas
      syringae pv. syringae. We have previously cloned a cDNA and a corresponding gene
      (Pir7b) whose transcripts accumulate upon infiltration with the resistance
      inducing bacteria. The putative encoded product Pir7b exhibits significant
      sequence similarity to two recently cloned hydroxynitrile lyases from Manihot
      esculenta (cassava) and Hevea brasisliensis, enzymes involved in the release of
      hydrogen cyanide from cyanogenic glycosides. As rice does not contain cyanogenic
      glycosides, a similar function of Pir7b appears unplausible. In order to
      functionally characterize the protein, recombinant Pir7b was produced in
      Escherichia coli and Saccharomyces cerevisiae. We show that recombinant Pir7b
      does not have hydroxynitrile lyase activity, but exhibits esterase activity
      towards naphthol AS-acetate. Using Pir7b-specific antibodies, we show that the
      protein accumulates in rice leaves inoculated with P. syringae pv. syringae. Both
      the recombinant and the authentic proteins have an apparent molecular mass of 32
      kDa (28.8 kDa calculated) and seem to be active as monomers. Pir7b esterase also
      exhibits sequence similarity to several expressed sequence tags of Arabidopsis
      thaliana, indicating that it belongs to a family of proteins widely occuring in
      plants.

PMID- 9652391
TI  - Blockage of apoptotic signaling of transforming growth factor-beta in human
      hepatoma cells by carboxyfullerene.
AB  - Transforming growth factor-beta (TGF-beta) has been shown to induce apoptosis in
      normal hepatocytes and hepatoma cells both in vivo and in vitro. However, the
      mechanism by which TGF-beta induces apoptosis is not clear. The antiapoptotic
      activity of antioxidants including N-acetyl-L-cysteine (Ac-Cys), ascorbic acid
      and a novel free radical scavenger, carboxyfullerene (C60) on TGF-beta-treated
      human hepatoma Hep3B cells was examined. Only the water-soluble hexacarboxylic
      acid derivative of C60 was found to prevent TGF-beta-induced apoptosis.
      Antiapoptotic activity of C60 correlated its ability to eliminate TGF-beta
      generated reactive oxygen species (ROSs). However, C60 did not interfere with TGF
      beta-activated PAI-1 promoter activity in the Hep3B cells. These results indicate
      that the signaling pathway of TGF-beta-induced apoptosis may be related to the
      generation of ROSs and may be uncoupled from the TGF-beta-activated gene promoter
      activity. Furthermore, the regioisomer of C60 with a C3 symmetry was more potent
      in protecting cells from apoptosis than that with a D3 symmetry, and the C3
      isomer had stronger interactions with lipid bilayers than the D3 isomer. The
      spectroscopic analysis revealed that the C3 isomer had stronger interactions with
      artificial lipid bilayers than the D3 isomer. Therefore, our study indicates that
      C60 may interact with membrane to eliminate TGF-beta-induced ROSs and to prevent
      apoptosis occur in human hepatoma cells.

PMID- 9652392
TI  - A depressant insect-selective toxin analog from the venom of the scorpion Leiurus
      quinquestriatus hebraeus--purification and structure/function characterization.
AB  - The scorpion venom-derived excitatory and depressant insect-selective polypeptide
      neurotoxins modify sodium conductance in insect neuronal membranes and differ
      greatly in their primary structures and symptoms induced in blow fly larvae. We
      report here the purification and characterization of a new insect selective
      toxin, LqhIT5. LqhIT5 is more similar to the excitatory toxins in its mode of
      action and the depressant toxins in its primary structure. This toxin is a single
      polypeptide composed of 61 amino acids that are cross linked by four disulfide
      bonds. When LqhIT5 is injected into blow fly larvae, a fast contraction paralysis
      occurs without depressant activity. No mammalian toxicity was detected by
      subcutaneous or intracranial injections of this toxin into mice. Sequence
      comparison of LqhIT5 and known depressant toxins shows a high degree of
      similarity among the amino acids located on the C-terminus of the toxins.
      However, there are some clear differences in the amino acids located close to the
      N-terminus of the toxins. By the aid of homology modeling, we demonstrated that
      these amino acids have the same orientation in the tertiary structure of the
      molecule and are exposed to the environment. The change in the mode of action of
      LqhIT5 (no depressant activity) by substitutions of a few amino acids located on
      a specific exposed area of the toxin shed a new light on the structure/function
      relationship of scorpion toxins. These results caution that similarity in the
      mechanism of action of scorpion toxins does not always follow from an overall
      similarity in sequence.

PMID- 9652393
TI  - In vitro activation of pro-phenol-oxidase by two kinds of pro-phenol-oxidase
      activating factors isolated from hemolymph of coleopteran, Holotrichia diomphalia
      larvae.
AB  - Previously, we purified and characterized a pro-phenol-oxidase (pro-PO) of 79 kDa
      from coleopteran insect, Holotrichia diomphalia larvae [Kwon et al. (1997) Mol.
      Cells 7, 90-97]. Here, we describe the identification of two pro-PO-activating
      factors (PPAF), named PPAF-I and PPAF-II, directly involved in the activation of
      the isolated pro-PO. When pro-PO was incubated with either PPAF-I or PPAF-II, no
      phenol oxidase activity was observed. However, incubation of pro-PO with both
      PPAF-I and PPAF-II specifically exhibited phenol oxidase activity. The purified
      PPAF-I with a molecular mass of 33 kDa on SDS/PAGE had characteristics of a
      serine protease. It exhibited amidase activity against fluorogenic peptide
      substrates, tert-butoxycarbonyl-phenylalanyl-seryl-arginyl-4-methylcoumaryl-7
      amide being the best among the substrates examined. The activity was completely
      inhibited by 0.02 mM p-nitrophenyl-p'-guanidinobenzoate HCl and
      diisopropylflurophosphate. The NH2-terminal sequence of PPAF-I had significant
      sequence similarity to those of serine proteases. On the other hand, the purified
      PPAF-II had a molecular mass of 40 kDa on SDS/PAGE and 400 kDa determined by gel
      filtration, indicating an oligomeric protein. The NH2-terminal sequence of PPAF
      II showed no similarity to known proteins. PPAF-II exhibited no amidase activity
      against the fluorogenic substrates. Reconstitution experiments and immunoblotting
      analysis using affinity-purified antibody against pro-PO demonstrated that PPAF-I
      first cleaves the intact pro-PO to an intermediate of 76 kDa with no phenol
      oxidase activity, and then, PPAF-I converts the intermediate to the active phenol
      oxidase of 60 kDa in the presence of PPAF-II. These results indicate that the
      activation of pro-PO system in hemolymph of H. diomphalia larvae is accomplished
      by at least two activating factors, a serine protease and a protein cofactor.

PMID- 9652394
TI  - Structure of the O-antigen of Vibrio cholerae O155 that shares a putative D
      galactose 4,6-cyclophosphate-associated epitope with V. cholerae O139 Bengal.
AB  - The O-specific polysaccharide of Vibrio cholerae 0155 was studied by sugar and
      methylation analyses, dephosphorylation with 48% hydrofluoric acid, 1H- and 13C
      NMR spectroscopy, including two-dimensional COSY, TOCSY, NOESY, and heteronuclear
      single-quantum coherence (HSQC) experiments. The following structure of the
      pentasaccharide repeating unit of the polysaccharide was established:
      carbohydrate sequence [see text]. An unusual component, D-galactose 4,6
      cyclophosphate, has been reported previously as a component of the capsular
      polysaccharide and O-antigen of V. cholerae O139 Bengal and appears to be
      responsible for the known serological cross-reactivity between V. cholerae O139
      and O155.

PMID- 9652395
TI  - A pancreas-specific glycosylated protein disulphide-isomerase binds to misfolded
      proteins and peptides with an interaction inhibited by oestrogens.
AB  - Using a cross-linking approach, we have demonstrated that radiolabeled model
      peptides or misfolded proteins specifically interact in vitro with two different
      luminal proteins in a crude extract from sheep pancreas microsomes. One of the
      proteins was identified as protein disulphide-isomerase (PDI), the other one was
      a related protein (PDIp). We have shown that PDIp was expressed exclusively in
      the pancreas. Interspecies conservation of PDIp was confirmed and, unlike other
      members of the PDI family, PDIp from various sources was found to be a
      glycoprotein. PDIp interacted with peptides and also a misfolded protein, but not
      with native proteins, suggesting that it might act as a molecular chaperone. The
      initial binding process was independent of the presence of Cys residues in the
      probed peptides. Certain oestrogens strongly inhibited the interaction between
      peptides and PDIp, with 17beta-oestradiol being the most potent inhibitor.

PMID- 9652396
TI  - Transcriptional regulation of the rat glutamine synthetase gene by tumor necrosis
      factor-alpha.
AB  - The expression of glutamine synthetase (GS) is induced in rat skeletal muscle
      cells (L-6) in response to treatment with the inflammatory cytokine tumor
      necrosis factor alpha (TNF-alpha). This paper reports the regulation of GS
      expression in rat skeletal muscle which expresses high levels of GS. TNF-alpha
      treatment leads to a 3-4-fold increase in GS activity in a dose-dependent and
      time-dependent manner. Northern-blot analysis of GS mRNA revealed an increased
      mRNA concentration, reaching a peak at 12 h in response to TNF-alpha treatment.
      To monitor transcriptional activation of GS by TNF-alpha, and to identify a TNF
      alpha-responsive element in the GS promoter, L6 cells were treated with TNF-alpha
      following transfection of GS-chloramphenicol-acetyltransferase (CAT) constructs.
      The first 251-bp fragment at the GS upstream sequence showed basal promoter
      activity, but failed to show any TNF-alpha-inducible activity. However, a 2.5-3
      fold induction was noted in constructs extending up to 1.1 kb. This data
      demonstrates that the rat GS gene is transcriptionally regulated by TNF-alpha and
      identifies a TNF-alpha-responsive region at the 5' flanking sequence of the GS
      gene.

PMID- 9652397
TI  - The mitochondrial phosphoglyceroyl-ATP-containing polymer, purinogen, is
      unchanged by cardiac ischaemia and reperfusion but may function in the regulation
      of free intracellular inorganic phosphate concentrations.
AB  - Previous work in our laboratory demonstrating large unexplained systematic
      variations in the heart contents of free adenine nucleotides led us to propose
      the existence of some unrecognised sequestered form and thence to the
      purification of very labile acid-insoluble oligomers which we characterised as
      oligo[3-phospho-glyceroyl-gamma-triphospho(5')adenosine(3')] , abbreviated to (PG
      ATP)n. More recently, we provided evidence that these oligomers appear to be the
      end chains of a complex polymer located in the mitochondrial intermembrane space
      of a number of rat tissues. We called this polymer purinogen and devised a means
      of assaying it quantitively [Patel, B., Sarcina, M. & Mowbray, J. (1994) Eur. J.
      Biochem. 220, 663-669]. Here we report measurements of purinogen in perfused
      hearts subjected to moderate and severe global ischaemia and reperfusion.
      Measurements of tissue and perfusate nucleotides, nucleosides and purine
      degradation products demonstrate that ischaemia led to the augmentation of the
      free nucleotide content by up to 30% and its re-sequestration on reperfusion in
      reversible but not in irreversible ischaemia. The purinogen content was unchanged
      by ischaemia or reperfusion implying the existence of some other unidentified
      storage pool. By contrast, glucose addition to glycolytically deprived hearts or
      removal of Pi from perfusion medium, conditions which might be expected to alter
      demand for intracellular Pi, led to the quantitative transfer of nucleotides
      between phosphate-rich purinogen and free nucleotides. The possibility that
      purinogen may act as a rapidly accessible reservoir of intracellular inorganic
      phosphate is discussed.

PMID- 9652398
TI  - Effect of dexamethasone on interleukin-1beta-(IL-1beta)-induced nuclear factor
      kappaB (NF-kappaB) and kappaB-dependent transcription in epithelial cells.
AB  - The production of inflammatory mediators by epithelial cells in inflammatory lung
      diseases may represent an important target for the anti-inflammatory effects of
      glucocorticoids. Nuclear factor-kappaB (NF-kappaB) is a major activator of
      inflammatory genes and has been proposed as a target for inhibition by
      glucocorticoids. We have used human pulmonary type-II A549 and airway epithelial
      BEAS-2B cells to investigate the effect of glucocorticoids on NF-kappaB
      regulation and kappaB-dependent transcription. In A549 cells following
      interleukin-1beta (IL-1beta) treatment, there was no effect of dexamethasone on
      the disappearance of I kappaB alpha protein, its subsequent reappearance 90-min
      later or the rapid induction of I kappaB alpha mRNA and transcription rate.
      Expression of p65 and p50/p105 proteins were also unaffected by dexamethasone. In
      addition, the rapid IL-1beta-induction of NF-kappaB DNA binding and p65 nuclear
      localisation was unaffected by short (1-6 hours) dexamethasone pre-treatments.
      Similarly, BEAS-2B cells showed no effect of dexamethasone on IL-1beta-induced NF
      kappaB (p50/p65). Stable transfection of a kappaB-dependent reporter in A549
      cells resulted in an 8-9-fold activation by IL-1beta or phorbol ester, that was
      repressed 30-40% by dexamethasone. However, in these cells, IL-1beta induction of
      inducible nitric oxide synthase, granulocyte-macrophage colony stimulating factor
      and cyclooxygenase-2 mRNA showed 70-90% repression by dexamethsone. We,
      therefore, conclude that in these epithelial cells, the repressive effects of
      glucocorticoids are not mediated by up-regulation of I kappaB alpha, decreased
      p50/p65 gene expression or inhibition of NF-kappaB DNA binding. Furthermore,
      since the maximal repression of IL-1beta or phorbol-ester-induced kappaB
      dependent transcription by dexamethasone was less than 40%, simple inhibition of
      kappaB-dependent transcription cannot by itself account for the full repressive
      effects of glucocorticoids observed in these cells.

PMID- 9652399
TI  - Cloning of two cDNAs encoding three small serine protease inhibiting peptides
      from the desert locust Schistocerca gregaria and analysis of tissue-dependent and
      stage-dependent expression.
AB  - This study describes the cloning of two cDNAs encoding three serine-protease
      inhibiting peptides, SGPI I, II and III, which were recently identified from
      ovarian extracts of the desert locust, Schistocerca gregaria. The first cDNA
      codes for the precursor polypeptides of SGPI I and SGPI II; the second encodes
      only a single inhibitor, SGPI III. Northern-blot analysis revealed an approximate
      length of 0.8 kb for SGPI-I/II mRNA and 0.6 kb for SGPI-III mRNA. The transcripts
      are present in several locust tissues, but they could not be detected in the
      midgut. The gene for SGPI-I/II is abundantly transcribed during all larval and
      adult stages, whereas SGPI-III mRNA is mainly present in adults. Northern-blot
      hybridization also revealed important changes in the SGPI-mRNA content during the
      molting cycle and during the adult reproductive cycle. Moreover, a differential
      hormonal control was observed in adult females which had been treated with
      precocene, juvenile hormone or ecdysone.

PMID- 9652400
TI  - Carbon-flux distribution in the central metabolic pathways of Corynebacterium
      glutamicum during growth on fructose.
AB  - Growth of Corynebacterium glutamicum on fructose was significantly less than that
      obtained on glucose, despite similar rates of substrate uptake. This was in part
      due to the production of overflow metabolites (dihydroxyacetone and lactate) but
      also to the increased production of CO2 during growth on fructose. These
      differences in carbon-metabolite accumulation are indicative of a different
      pattern of carbon-flux distribution through the central metabolic pathways.
      Growth on glucose has been previously shown to involve a high flux (> 50% of
      total glucose consumption) via the pentose pathway to generate anabolic reducing
      equivalents. NMR analysis of carbon-isotope distribution patterns of the
      glutamate pool after growth on 1-13C- or 6-13C-enriched fructose indicates that
      the contribution of the pentose pathway is significantly diminished during
      exponential growth on fructose with glycolysis being the predominant pathway (80%
      of total fructose consumption). The increased flux through glycolysis during
      growth on fructose is associated with an increased NADH/NAD+ ratio susceptible to
      inhibit both glyceraldehyde-3-phosphate dehydrogenase and pyruvate dehydrogenase,
      and provoking the overflow of metabolites derived from the substrates of these
      two enzymes. The biomass yield observed experimentally is higher than can be
      estimated from the apparent quantity of NADPH associated with the pentose pathway
      and the flux through isocitrate dehydrogenase, suggesting an additional reaction
      yielding NADPH. This may involve a modified tricarboxylic acid cycle involving
      malic enzyme, expressed to significantly higher levels during growth on fructose
      than on glucose, and a pyruvate carboxylating anaplerotic enzyme.

PMID- 9652401
TI  - Sequence and structure of the human 6-phosphofructo-2-kinase/fructose-2,6
      bisphosphatase heart isoform gene (PFKFB2).
AB  - 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2) is a
      bifunctional enzyme that catalyzes the synthesis and degradation of Fru-2,6-P2, a
      key regulator of glycolysis. In mammals, several genes have been found to code
      for different PFK-2/FBPase-2 isoforms that differ in tissue distribution and
      enzymatic activities. In the present study, we report the characterization of the
      PFK-2/FBPase-2 heart isoform gene in humans (PFKFB2), including a full analysis
      of repetitive sequences and potential transcription binding sites. The genomic
      sequence of the PFKFB2 gene spans 22,485 bp and contains 15 exons. Heart cDNA
      analysis shows that PFKFB2 codes for a protein of 505 amino acids with a deduced
      molecular mass of 58,849 Da. Comparison of the human PFKFB2 gene to the
      homologous genes in rat and ox outlines a significant conservation of the intron
      exon structure, sequence of 5' and 3' flanking regions, and simple sequence
      repetitive element positions. Most important, the human heart PFK-2/ FBPase-2
      protein was found to retain all the important regulatory sites, as well as the
      catalytic and substrate binding sites identified in the rat and bovine heart
      isoforms, suggesting that the human enzyme is regulated in a manner similar to
      that observed in these organisms.

PMID- 9652402
TI  - Evidence of an overlap between the two half-sites of UAS1-B/CYC1--a new model for
      Cyp1p (Hap1p) DNA binding.
AB  - Cyp1p (Hap1p) is a yeast transcriptional regulator belonging to the zinc-cluster
      family. CGGNNNTANCGG was identified by PCR selection as the DNA sequence allowing
      its optimal binding. Nevertheless, this sequence is not a consensus sequence, the
      simultaneous presence of the two CGGs and the TA generally not being found in the
      known natural Cyp1p targets. In fact, our previous studies showed that the
      mechanism of Cyp1p DNA binding was target dependent. Data concerning the binding
      of Cyp1p to the UAS1-B/CYC1 are presented here. This target, containing the
      CGGGGTTTACGG sequence, was found to present the particular ability of stabilizing
      the binding of only one molecule of some monomeric Cyp1p fragments. This property
      was used to investigate the actual contribution of the TT and CGG sequences in
      the binding of Cyp1p. Our results indicate that each CGG belongs to a different
      half-site and, in contrast to a previous hypothesis, that the T nucleotide
      located four bases downstream from the left CGG is essential for the binding of
      one monomer to each half-site. The two half-sites of the UAS1-B/CYC1 thus
      overlap.

PMID- 9652403
TI  - Molecular cloning, gene structure and expression profile of mouse C1 inhibitor.
AB  - The gene encoding C1 inhibitor, the major control element of activation of the
      classical pathway of complement and a major inhibitor of several plasma serine
      proteases, has been studied only in man, where deficiency of C1 inhibitor results
      in the dominantly transmitted disease hereditary angioedema. Full-length mouse C1
      inhibitor cDNA and genomic clones were isolated and characterized as a first step
      towards the complete characterization of the pattern of C1 inhibitor expression
      and the production of an animal model of C1 inhibitor deficiency. Restriction
      enzyme and sequence analyses of a full-length genomic clone demonstrated that the
      mouse gene has the same structure as the human homologue, but differs in size (9
      kb versus 17 kb), mostly due to the presence of repetitive Alu elements in the
      human gene. Sequence comparisons in the promoter region indicate important
      similarities, i.e. the absence of a TATA box, the presence of an initiator
      sequence encompassing the transcription-start site and of a gamma-interferon
      activated sequence (GAS) element at position -124 of the human sequence. A
      stretch of about 100 nucleotides in intron 1 reveals an unusually high degree of
      conservation for non-coding sequences and contains non-canonical but conserved
      tandemly arranged GAS elements at positions 369 and 388 of the human sequence.
      This finding supports the conclusions of functional studies on the human C1INH
      gene indicating a role of this region in modulation of transcription by
      interferons. The profile of C1 inhibitor expression in mouse liver, lung, heart,
      kidney, spleen and brain was determined by quantitative northern blot analysis.

PMID- 9652404
TI  - Primary structure and high expression of human agrin in basement membranes of
      adult lung and kidney.
AB  - Agrin is a heparan sulfate proteoglycan involved in the development of the
      neuromuscular junction during embryogenesis. In addition to this well
      characterized function, agrin may have additional functions in other tissues and
      during other stages in development. In this study we present the cDNA sequence of
      human agrin, and demonstrate a high agrin content in adult basement membranes.
      The N-terminal domain of human agrin is highly similar to that of chick agrin,
      suggesting a similar function in laminin binding. The presence of three SGXG
      sequences supports serine-linked glycosylation of the core protein, two sites
      being particularly favorable for heparan sulfate attachment. Comparison of levels
      of agrin mRNA in fetal and adult human tissues showed a remarkable upregulation
      in adult kidney and lung. In both tissues truncated agrin transcripts were
      detected, lacking the region that encodes the laminin-binding domain. The high
      transcription levels in lung and kidney corresponded with the accumulation of
      agrin in the alveolar and glomerular basement membranes, suggesting a filtration
      associated function. These data provide new directions for investigating the role
      of agrin in its different physiological environments, including the basement
      membranes of the neuromuscular junction, kidney and lung.

PMID- 9652405
TI  - Oligonucleotide facilitators enable a hammerhead ribozyme to cleave long RNA
      substrates with multiple-turnover activity.
AB  - Trans-acting hammerhead ribozymes are usually efficient in cleaving short RNA
      model substrates under both single-turnover and multiple-turnover conditions. In
      contrast, when long RNAs are the substrates, the cleavage efficiency of these
      ribozymes decreases, including a loss of multiple-turnover activity in many
      cases. Since target substrates for potential therapeutical purposes are mostly
      long RNAs, a multiple-turnover cleavage of long RNAs would essentially increase
      the efficiency of hammerhead ribozymes. Therefore, we explored if oligonucleotide
      facilitators, capable of enhancing multiple-turnover activity with short
      substrates, can also affect or cause multiple turnover with long substrates. We
      examined the effects of 12-base and 24-base oligonucleotide facilitators on the
      multiple-turnover activity with substrates of different length containing 39-,
      452- and 942-base sequences of the human tissue factor (HTF) mRNA. In the absence
      of facilitator, the ribozyme cleaved only the 39-base substrate with multiple
      turnover activity, but not the long 452-base and 942-base substrates. However,
      facilitator addition enabled the ribozyme to cleave even the 452-base and the 942
      base substrates with multiple-turnover activity. All facilitators tested showed a
      remarkable activating effect with the long substrates. The data demonstrate that
      a hammerhead ribozyme which, by itself, can only act as a single-turnover
      catalyst with long substrates, can be switched by facilitators into a multiple
      turnover catalyst. Thus, the inactivation of long target RNAs in multiple
      turnover reactions may be achieved by addition of oligonucleotide facilitators.

PMID- 9652406
TI  - Different derivations of knowledge-based potentials and analysis of their
      robustness and context-dependent predictive power.
AB  - The possibility of defining effective potentials from known protein structures,
      which are sufficiently accurate to be used for protein-structure-prediction
      purposes, is investigated. Three types of distance potentials and three types of
      backbone torsion potentials are defined, based on propensities of amino acid
      pairs to be separated by a given spatial distance or to be associated to a
      backbone torsion angle domain. Their differences reside in the way the physical
      correlations between the amino acids and the conformational states are extracted
      from the bulk interactions due to the presence of many residues in a protein. For
      the distance potentials, a physical meaning can be associated to the different
      definitions, given that some of the potentials favor hydrophobic interactions and
      others favor interactions between oppositely charged residues. The performance of
      the different torsion and distance potentials in structure prediction procedures,
      in particular native-fold recognition and evaluation of protein stability changes
      upon point mutations, is analyzed. It appears to differ according to the specific
      proteins and protein environments. In particular, one of the distance potentials
      performs better than the others for membrane proteins and in protein regions
      involving charged residues, but less well in other protein regions. Furthermore,
      the dependence of the potentials on the characteristics of the proteins from
      which they are derived is analyzed. It is shown that the dependence of the
      potentials on the length, amino acid composition and secondary-structure content
      of the proteins from the dataset is either very limited or rather strong,
      according to the type of potential. The results obtained suggest that the main
      problem limiting the performance of database-derived potentials is their lack of
      universality: each potential describes with satisfactory accuracy only the
      interactions present in certain protein environments.

PMID- 9652407
TI  - Transferrins--a mechanism for iron uptake by lactoferrin.
AB  - Iron uptake by bovine lactoferrin from nitrilotriacetatoFe(III) [FeN(Ac)3] in the
      presence of bicarbonate has been investigated at pH 7.1-8.7. Deprotonated
      apolactoferrin interacting with bicarbonate or carbonate extracts iron from
      nitrilotriacetatoFe(III); the direct second-order rate constant k1 = (4.90 +/-
      0.20)x10(4) M(-1) s(-1), a reverse second-order rate constant k(-1) = (1.80+/
      0.05)x10(5) M(-1) s(-1), and the iron-exchange equilibrium constant K1 = 0.25+/
      0.05. The newly formed iron-protein complex loses a single proton with proton
      dissociation constant K3a = (17+/-0.5) nM, then undergoes a modification in its
      conformation followed by the loss of two or three protons; the first-order rate
      constant k2 = (1.0+/-0.10) s(-1). This induces a new modification in the
      conformation; the first-order rate constant k3 = (8.75+/-0.40)x10(-3) s(-1). This
      second modification in conformation controls the rate of iron uptake by the N
      site of the protein and is followed by a single proton loss; K5a = 8.0 nM.
      Finally, the holoprotein or the monoferric lactoferrin in their final
      equilibrated states are produced by a third modification in the conformation
      occurring in about 9000 s. The mechanism of iron uptake by lactoferrin is very
      similar to that of serum transferrin with a cooperativity between the C and N
      sites upon iron uptake but with lower rates, higher affinities and at least one
      more proton loss involved. These differences may be the result of slight
      discrepancies in the intimate structures of binding sites for serum transferrin
      and lactoferrin. In order to analyse the cooperativity between these iron-binding
      sites, the three-dimensional position of the chain of amino acid residues
      separating the N and C lobes of human apo-, holo- and dicopper-lactoferrin have
      been compared by the recognition of the three-dimensional shape dissimilarity
      program. The interlobe peptides of human hololactoferrin and apolactoferrin
      showed only 75.5 % tridimensional similarity, indicating that iron uptake affects
      the three-dimensional structure of the interlobe chain.

PMID- 9652408
TI  - Molecular characterization of cyanophycin synthetase, the enzyme catalyzing the
      biosynthesis of the cyanobacterial reserve material multi-L-arginyl-poly-L
      aspartate (cyanophycin).
AB  - Cyanophycin (multi-L-arginyl-poly-L-aspartate), a water-insoluble reserve polymer
      of cyanobacteria, is a product of nonribosomal peptide synthesis. The
      purification of cyanophycin synthetase of the cyanobacterium Anabaena variabilis
      is described. In sodium dodecylsulfate/polyacrylamide gel electrophoresis, the
      enzyme preparation shows one band with an apparent molecular mass of 100 kDa. The
      native enzyme has an apparent molecular mass of approximately 230 kDa, as
      determined by size-exclusion chromatography, suggesting that the active form is a
      homodimer. During catalysis, ATP is converted to ADP. The gene coding for
      cyanophycin synthetase has been identified in the sequenced genome of
      Synechocystis sp. PCC 6803. The C-terminal 60% of the deduced amino acid sequence
      of cyanophycin synthetase show sequence similarity to enzymes of the superfamily
      of ligases involved in the biosynthesis of murein and of folyl-poly(gamma
      glutamate). Cells of Escherichia coli harbouring the gene on a plasmid express
      active synthetase and accumulate cyanophycin-like material. The results prove
      that a single enzyme catalyzes the de novo synthesis of cyanophycin.

PMID- 9652409
TI  - Purification, characterization and cloning of an aspartic proteinase inhibitor
      from squash phloem exudate.
AB  - Phloem exudate from squash fruit contains heat-inactivated material which
      inhibits pepsin activity. This inhibitory activity was purified by mild acid
      treatment, chromatography on trypsin-agarose, Sephadex G-75 and reverse-phase
      HPLC, resulting in the elution of three peaks with pepsin-inhibitory activity. N
      terminal sequencing indicated a common sequence of MGPGPAIGEVIG and the presence
      of minor species with seven- or two-amino-acid N-terminal extensions beyond this
      point. Microheterogeneity in this end sequence was exhibited within and between
      two preparations. Internal sequencing of a major peak after a trypsin digestion
      gave the sequence FYNVVVLEK. The common N-terminal sequence was used to design a
      degenerate primer for 3' rapid amplification of cDNA ends and cDNA clones
      encoding two isoforms of the inhibitor were obtained. The open reading frames of
      both cDNAs encoded proteins (96% identical) which contained the experimentally
      determined internal sequence. The amino acid content calculated from the
      predicted amino acid sequence was very similar to that measured by amino acid
      analysis of the purified inhibitor. The two predicted amino acid sequences (96
      residues) had neither similarity to any other aspartic proteinase inhibitor nor
      similarity to any other protein. The inhibitors have a molecular mass of 10,552
      Da, measured by matrix-assisted laser-desorption ionisation time-of-flight mass
      spectrometry and approximately 10,000 Da by SDS/PAGE, and behave as dimers of
      approximately 21,000 Da during chromatography on Superdex G-75 gel-filtration
      medium. The calculated molecular masses from the predicted amino acid sequences
      were 10,551 Da and 10,527 Da. The inhibitor was capable of inhibiting pepsin (Ki
      = 2 nM) and a secreted aspartic proteinase from the fungus Glomerella cingulata
      (Ki = 20 nM). The inhibitor, which is stable over acid and neutral pH, has been
      named squash aspartic proteinase inhibitor (SQAPI).

PMID- 9652410
TI  - Structural determination of the O-antigenic polysaccharide from Escherichia coli
      O141.
AB  - The structure of the O-antigenic polysaccharide from Escherichia coli O141 has
      been determined. NMR spectroscopy and sugar and methylation analyses were the
      principal methods used. The sequence of the sugar residues could be determined by
      NOESY and heteronuclear multiple-bond connectivity (HMBC-) NMR experiments. The
      polysaccharide is composed of pentasaccharide repeating units with 1 O-acetyl
      group/repeating unit. The following structure, where Rha is 6-deoxymannose is
      concluded: carbohydrate sequence [see text].

PMID- 9652411
TI  - Dextran strongly increases the Michaelis constants of oxidative phosphorylation
      and of mitochondrial creatine kinase in heart mitochondria.
AB  - Macromolecules restore the morphological changes which occur upon isolation of
      mitochondria in normally used isolation media. It was shown that in the presence
      of dextrans the permeability of mitochondrial outer membrane for adenine
      nucleotides decreases which may have considerable implications for the transport
      of ADP into the mitochondria. In this study the effect of dextran on the apparent
      Michaelis constants of oxidative phosphorylation and mitochondrial creatine
      kinase (mi-CK) of rat heart mitochondria was investigated. Mitochondria were
      isolated either in normally used isolation media or in the additional presence of
      15% dextran 20 in order to avoid changes in the oncotic conditions on the
      mitochondria during preparation and investigation. Except for an increased
      contamination with extramitochondrial ATPases the basic functional properties of
      these mitochondria were normal. With oxygraphic measurements it was found that
      Km(ADP) of oxidative phosphorylation increased from 16 +/- 4 microM ADP (without
      dextran) to 50 +/- 15 microM (15% dextran 20) and to 122 +/- 62 microM (25%
      dextran 20) irrespective of the mode of preparation of the mitochondria. Using
      spectrophotometric measurements the effect of dextran on the Km(ATP) of mi-CK was
      investigated in three systems (a) as soluble enzyme, (b) bound to mitoplasts, (c)
      and in intact rat heart mitochondria. The addition of 10% dextran had no effect
      on kinetic properties of solubilized mi-CK. In intact heart mitochondria,
      however, the addition of dextran caused an augmentation of Km(ATP) from 332 +/-
      91 microM (control) to 525 +/- 150 microM ATP (10% dextran) and 641 +/- 160
      microM ATP (30% dextran). In mitoplasts the effect of dextran disappeared
      (control, 230 +/- 19 microM ATP; 10% dextran, 238 +/- 28 microM ATP) indicating
      that the outer mitochondrial membrane is a prerequisite for the modulation of the
      transport of adenine nucleotides into the intermembrane space by macromolecules.
      To investigate the effects of viscosity of dextran solutions on the diffusion of
      adenine nucleotides across the outer membrane, dextrans with different molecular
      size (20, 40 70 and 500 kDa) were used. The viscosity of the 10% solutions
      drastically increased with the molecular size of the dextrans used, but the
      effects of different dextran solutions on the kinetic constants were the same.
      From these results it was concluded that neither the viscosity nor the molar
      concentration but the content of macromolecules (mass/vol.) correlates with
      restrictions of diffusion into the intermembrane space of mitochondria with
      intact outer membranes. Assuming that a dextran concentration of 15% mimicks the
      intracellular oncotic pressure on mitochondria in vivo, the apparent Km(ATP) of
      oxidative phosphorylation within the intact cell seems to be about 50 microM ADP
      which is somewhat higher than the cytoplasmic free ADP concentration as reported
      for the intact heart.

PMID- 9652412
TI  - Transport of LDS-751 from the cytoplasmic leaflet of the plasma membrane by the
      rhodamine-123-selective site of P-glycoprotein.
AB  - P-glycoprotein is an ATP-dependent transporter of an extremely wide variety of
      lipophilic compounds. We showed previously [Shapiro, A. B. & Ling, V. (1997a)
      Eur. J. Biochem. 250, 130-137] that P-glycoprotein contains two drug transporting
      sites, dubbed H (for Hoechst 33342-selective) and R (for rhodamine-123
      selective), that interact with positive cooperativity. The H site transports 2-[2
      (4-ethoxyphenyl)-6-benzimidazolyl]-6-(1-methyl-4-piperazyl)be nzimidazole
      (Hoechst 33342) from the cytoplasmic leaflet of the plasma membrane to the
      aqueous extracellular medium [Shapiro, A. B. & Ling, V. (1997b) Eur. J. Biochem.
      250, 122-129]. The environment from which the R site transports its substrates is
      unknown. In this paper, we used the fluorescent DNA dye 2-[4-[4
      (dimethylamino)phenyl]-1,3-butadienyl]-3-ethylbenzothiazolium perchlorate (LDS
      751), a substrate of the R site, to address this issue. LDS-751 which, like
      Hoechst 33342, exhibits lipid-dependent fluorescence and slow transleaflet
      diffusion, allowed us to use the same methodology that we used for the H site to
      study the location of the R site. As with Hoechst 33342, the specific initial
      rate of LDS-751 transport by P-glycoprotein-rich, isolated plasma membrane
      vesicles from CH(R)B30 cells was directly proportional to the amount of membrane
      bound LDS-751 and inversely proportional to the concentration of free, aqueous
      LDS-751. This result demonstrates that the R site of P-glycoprotein transports
      LDS-751 out of the lipid membrane. The slight decrease, instead of an increase,
      in the initial rate of active transport of LDS-751 with the amount of time
      elapsed for slow diffusion of LDS-751 from the cytoplasmic leaflet to the
      extracellular leaflet indicates that the R site of P-glycoprotein removes LDS-751
      from the cytoplasmic leaflet of the plasma membrane. Thus, both known drug
      transporting sites of P-glycoprotein remove their substrates from the cytoplasmic
      leaflet. Since all of the P-glycoprotein substrates we have examined so far are
      recognized by one or both of the two known drug-transporting sites, these two
      sites in the cytoplasmic leaflet of the plasma membrane may be able to account
      for all substrate transport by P-glycoprotein.

PMID- 9652413
TI  - Stoichiometry of coupling of rhodamine 123 transport to ATP hydrolysis by P
      glycoprotein.
AB  - In order to describe the transport mechanism of P-glycoprotein, it is essential
      to know the coupling ratio, i.e. the moles substrate transported/mole ATP
      hydrolyzed. P-glycoprotein couples ATP hydrolysis at two ATP-binding sites to
      transport of a wide variety of neutral or cationic lipophilic compounds.
      Previously published coupling ratios have fallen within the range 0.02-0.8 mol
      substrate transported/mol ATP hydrolyzed. We studied the energetics of transport
      by P-glycoprotein, performing quantitative measurements of the rates of ATP
      hydrolysis and transport of rhodamine 123 by P-glycoprotein, using isolated P
      glycoprotein-rich plasma membrane vesicles. The continuous fluorescence-based
      assay of rhodamine 123 transport allowed accurate measurement of initial
      transport rates. Since we measured uptake of rhodamine 123 into the vesicles as a
      loss of fluorescence, we avoided the problem of high background due to substrate
      binding to the membranes. The coupling ratio of the transport reaction increased
      as the rhodamine 123 concentration increased, showing that the basal ATPase
      activity of P-glycoprotein was progressively recruited for rhodamine 123
      transport. Both of the previously identified transport sites of P-glycoprotein
      [Shapiro, A. B. & Ling, V. (1997a) Eur J. Biochem. 250, 130-137] were involved in
      transport of saturating concentrations of rhodamine 123. At saturating rhodamine
      123 and 0.3 mM ATP, the coupling ratio was 0.83, suggesting a mechanistic
      coupling ratio of 1. Interestingly, the coupling ratio decreased as the ATP
      concentration increased so that, at 1.5 mM, close to the cytoplasmic
      concentration of ATP, the coupling ratio was 0.57. The physiological significance
      of this effect is not yet understood.

PMID- 9652415
TI  - Role of the actin cytoskeleton in regulating the outer phosphatidylethanolamine
      levels in yeast plasma membrane.
AB  - Transbilayer phosphatidylethanolamine (PtdEtn) movements in the plasma membrane
      of Saccharomyces cerevisiae are regulated by an ATP-dependent, protein-mediated
      process(es). To examine whether this process is influenced by the actin
      cytoskeleton, we have studied the PtdEtn translocation in S. cerevisiae cells
      after treatment with microfilament disrupting and microtubule-disrupting agents.
      PtdEtn translocation was studied by measuring the external PtdEtn levels, using
      fluorescamine as the external membrane probe, in the ATP-depleted, ATP-depleted
      and repleted, and N-ethylmaleimide-treated cells. The microfilaments and
      microtubules were disrupted by treatment with various cytochalasins and
      colchicine (or benomyl) respectively PtdEtn translocation became abnormal in the
      cytochalasin-treated cells but not in cells that were treated with microtubule
      disrupting agents, such as colchicine or benomyl. These results have been
      interpreted to suggest that the actin cytoskeleton is involved in regulating the
      PtdEtn translocase activity in the yeast cell plasma membrane.

PMID- 9652414
TI  - Control of oxidative phosphorylation, gluconeogenesis, ureagenesis and ATP
      turnover in isolated perfused rat liver analyzed by top-down metabolic control
      analysis.
AB  - We have analyzed the control exerted by the pathways of oxidative
      phosphorylation, gluconeogenesis, ureagenesis, and maintenance ATP consumption
      over each other's rates in isolated, perfused rat liver using top-down metabolic
      control analysis. The livers from fasted rats were perfused with 3
      hydroxybutyrate as respiratory substrate, lactate as substrate for
      gluconeogenesis, and ammonium as substrate for urea synthesis, in conditions
      where these pathways were only linked by their common intermediates: ATP, ADP,
      and Pi. The rates of oxygen consumption, glucose and urea synthesis were measured
      continuously. The pathways were perturbed either by adding specific inhibitors or
      by adding new pathways that consumed ATP, and the relative changes in pathway
      rates were used to calculate the flux control coefficients of each pathway over
      all pathway rates. When the liver was in a relatively inactive metabolic state,
      where ATP was only being used by the maintenance ATP-consuming pathways, then
      essentially all the control over ATP production and consumption was located in
      the maintenance ATP consumers with ATP production having no control. Whereas,
      when the liver was in a highly active state using extra ATP for both glucose and
      urea synthesis, then ATP production (from oxidative phosphorylation) had strong
      control over its own rate and the rates of glucose and urea synthesis, but
      gluconeogenesis and ureagenesis still had strong control over their own rates and
      negative control over each others rates, i.e. they competed for the limited ATP
      supply. The rate of the maintenance ATP consumers is remarkably insensitive to
      changes in ATP production and consumption, but exerts considerable control over
      all other pathways. These results indicate that the general assumption that the
      rates of ATP production and consumption are controlled exclusively by ATP
      consumers is false under conditions where a significant amount of ATP is used for
      biosynthetic processes, such as glucose and urea synthesis, and indicate that the
      latter processes may be partly controlled by regulators of ATP production and by
      other ATP-consuming pathways.

PMID- 9652416
TI  - Cervical antibody responses to a herpes simplex virus type 2 glycoprotein subunit
      vaccine.
AB  - Effective vaccines against genital herpes simplex virus type 2 (HSV-2) may need
      to induce genital tract immune responses. To determine local antibody responses
      to HSV-2 glycoproteins gB2 and gD2 in an intramuscular subunit vaccine, cervical
      secretions from HSV-seronegative women and HSV-1-seropositive women were tested
      for IgG and IgA to gB2 and gD2 by enhanced chemiluminescence Western blot. Most
      (94%) of the seronegative subjects developed cervical IgG to gB2, IgG to gD2, and
      IgA to gB2; 72% developed IgA to gD2. All HSV-1-seropositive subjects had
      cervical IgG responses to vaccine gB2 and gD2, 85% had IgA responses to gB2, and
      50% had IgA responses to gD2. Responses were more rapid and titers more
      consistently sustained in the HSV-1-seropositive women. Further, vaccination
      resulted in cervical IgG and IgA titers comparable to those to HSV-2 gB2 and gD2
      in response to recurrent HSV-2 genital infection.

PMID- 9652417
TI  - Limited variability of glycoprotein gene sequences and neutralizing targets in
      herpes simplex virus type 2 isolates and stability on passage in cell culture.
AB  - Nucleotide sequence analyses of polymerase chain reaction-amplified genes were
      performed to determine whether adaptation of herpes simplex virus type 2 to
      replication in cultured cells or in internal organs during neonatal disseminated
      disease results in selection of variants with altered forms of three
      glycoproteins (gB, gC, or gD) that influence virus entry into cells. No
      variations in sequence were noted as a consequence of in vitro passage or
      replication in different organs. Five viruses from different subjects differed
      with respect to gB, gC, and gD gene sequences, expressing four distinct forms of
      gB, three of gC, and two of gD. These differences did not confer resistance to
      neutralization by guinea pig or human antisera from subjects immunized with
      recombinant gB or gD vaccines and may not be consequential for vaccine
      development.

PMID- 9652418
TI  - Granulocyte-macrophage colony-stimulating factor expressed in T cells mediates
      immunity against herpes simplex virus type 1 encephalitis.
AB  - A model of herpes simplex virus type 1 (HSV-1) infection was developed in rats to
      study systemic immune responses elicited by intravitreous inoculation of the
      virus. HSV-1 inoculation led to distinct granulocyte-macrophage colony
      stimulating factor (GM-CSF)-producing memory T cells, which did not develop in
      rats inoculated with either HSV-1 intraperitoneally or inactivated HSV-1
      intravitreously. On subsequent intraperitoneal viral boosting, systemic GM-CSF
      production was elicited as a secondary immune response that caused
      neutroeosinophilia. To examine the role of GM-CSF in anti-herpetic immunity,
      cytokine-producing and -nonproducing rats were intravitreously challenged with
      HSV-1, which causes lethal encephalitis. Only intravitreously primed rats were
      protected upon production of GM-CSF. Furthermore, pretreatment with recombinant
      GM-CSF protected unimmunized rats against the encephalitis. It is thus strongly
      suggested that the production of GM-CSF leads to anti-HSV-1 immunity against the
      transneuronal spread of challenged HSV-1 within the visual system.

PMID- 9652420
TI  - Identification of the Oka strain of the live attenuated varicella vaccine from
      other clinical isolates by molecular epidemiologic analysis.
AB  - A method was developed to distinguish the Oka vaccine strain of varicella-zoster
      virus (VZV) from other clinical isolates. The molecular characteristics of 52
      clinical isolates from varicella or zoster patients with no history of VZV
      vaccination and the Oka strain, including vaccine and parental viruses, were
      analyzed by PstI cleavage of the PstI site-less (PSL) region. This was followed
      by single-strand conformational polymorphism (SSCP) after polymerase chain
      reaction amplification of repeating region 2 (R2). Most of the clinical isolates
      tested, especially recent isolates, had a PstI site in the PSL region, but the
      Oka strain did not. The SSCP patterns of R2 in Oka strain virus differed from
      those of other viruses. These results suggest that analysis of the PstI site
      followed by SSCP of R2 will be useful for identifying the Oka vaccine virus in
      isolates.

PMID- 9652419
TI  - T cells specific for the triggering virus infiltrate the eye in patients with
      herpes simplex virus-mediated acute retinal necrosis.
AB  - Acute retinal necrosis (ARN) is a rare, potentially blinding retinal disease
      resulting from ocular infections with herpes simplex virus (HSV) or varicella
      zoster virus (VZV). To determine the antigen specificity and functional
      characteristics of ocular infiltrating T cells in ARN, T cells were isolated and
      expanded nonspecifically from intraocular fluid (IOF) samples from 2 patients
      with HSV-1- and 3 with VZV-mediated ARN. HSV-specific T cell reactivity could be
      detected only in the IOF-derived T cell lines (TCLs) of the 2 patients with HSV
      mediated ARN. These TCLs consisted of both HSV type-common and type-specific CD4+
      and CD8+ T cell clones (TCCs) with differential T cell receptor usage.
      Irrespective of their phenotype, the TCCs were cytolytic and secreted interferon
      gamma, tumor necrosis factor-alpha, interleukin-4, and interleukin-5. In both
      patients, the antigen specificity of a substantial number of HSV-1-specific TCCs
      could be mapped to approximately 0.67-0.73 HSV-1 map units. The data presented
      suggest the contribution of T cells, specific for the triggering virus, to the
      pathogenesis of ARN.

PMID- 9652421
TI  - Association between MHC class II alleles and clearance of circulating hepatitis C
      virus. Members of the Trent Hepatitis C Virus Study Group.
AB  - The frequencies of HLA class I antigens and class II haplotypes were compared in
      subjects with previous (polymerase chain reaction [PCR]-negative) or with
      persistent (PCR-positive) hepatitis C virus (HCV) infection and in HCV patients
      with mild versus severe histologic activity scores on liver biopsy. The DRB1*11
      allele group was found in 11 (31.4%) of 35 subjects with previous infection and
      in 11 (8.2%) of 135 subjects with persistent infection (P < .001). The DQB1*0301
      allele was found in 18 (51.4%) of 35 subjects with previous infection and in 33
      (24.4%) of 135 patients with persistent infection (P < .002). Both observations
      remained significant after correction for multiple testing. No significant
      association was shown between severity of disease and any HLA class I or II type.
      Thus, the HLA class II alleles DRB1*11 and DQB1*0301 are associated with
      clearance of circulating HCV.

PMID- 9652422
TI  - Human papillomavirus, anal squamous intraepithelial lesions, and human
      immunodeficiency virus in a cohort of gay men.
AB  - Cross-sectional associations between human papillomavirus (HPV), anal squamous
      intraepithelial lesions (SIL), and human immunodeficiency virus (HIV) were
      studied in a cohort of gay men. HPV DNA was detected by generic and type-specific
      polymerase chain reaction (PCR) probes and hybrid capture assay (HC). HPV virus
      load was estimated by HC relative light unit (RLU) ratio. HPV prevalence, number
      of HPV types detected, and HC RLU ratios were each greater in HIV-positive than
      HIV-negative participants. Further, among HIV-positive men, HC RLU ratio was
      inversely associated with CD4 cell count. SIL was more frequent in HIV-positive
      participants, particularly those with a CD4 cell count <200/microL and was
      positively associated with HPV. Men with a high HC RLU ratio were nearly 3 times
      more likely to have SIL than were those both PCR- and HC-negative. These data
      support that HIV augments HPV-associated anal disease in this population.

PMID- 9652423
TI  - Pandemic versus epidemic influenza mortality: a pattern of changing age
      distribution.
AB  - Almost all deaths related to current influenza epidemics occur among the elderly.
      However, mortality was greatest among the young during the 1918-1919 pandemic.
      This study compared the age distribution of influenza-related deaths in the
      United States during this century's three influenza A pandemics with that of the
      following epidemics. Half of influenza-related deaths during the 1968-1969
      influenza A (H3N2) pandemic and large proportions of influenza-related deaths
      during the 1957-1958 influenza A (H2N2) and the 1918-1919 influenza A (H1N1)
      pandemics occurred among persons <65 years old. However, this group accounted for
      decrementally smaller proportions of deaths during the first decade following
      each pandemic. A model suggested that this mortality pattern may be explained by
      selective acquisition of protection against fatal illness among younger persons.
      The large proportion of influenza-related deaths during each pandemic and the
      following decade among persons <65 years old should be considered in planning for
      pandemics.

PMID- 9652424
TI  - Evolution of cytotoxic T lymphocyte responses to human immunodeficiency virus
      type 1 in patients with symptomatic primary infection receiving antiretroviral
      triple therapy.
AB  - The impact of highly active antiretroviral treatment (HAART) on anti-human
      immunodeficiency virus (HIV) cytotoxic T lymphocytes (CTL) was studied in 17
      patients with recent symptomatic HIV-1 primary infection receiving triple
      combination therapy. Anti-HIV CTL were initially detected in 15 patients. In 6,
      CTL disappeared rapidly and persistently after initiation of therapy. Most of
      them had a rapid and sustained decrease in plasma HIV RNA to undetectable levels.
      Conversely, in 6 other patients, CTL remained detectable, which was associated
      with a less efficient control of viral replication. In 3 others, CTL disappeared
      only transiently, without clear correlation with the virologic profile.
      Altogether, despite individual variations, there was a positive correlation
      between viral replication and anti-HIV-1 cytotoxicity in most subjects,
      suggesting that the persistence of viral antigens is the main determinant for the
      maintenance of CTL activity. This raises the question of the potential benefit of
      anti-HIV CTL induction by immunotherapy in acute seroconverters treated by HAART.

PMID- 9652425
TI  - Immunologic responses associated with 12 weeks of combination antiretroviral
      therapy consisting of zidovudine, lamivudine, and ritonavir: results of AIDS
      Clinical Trials Group Protocol 315.
AB  - Human immunodeficiency virus (HIV)-1 infection is associated with progressive
      cell-mediated immune deficiency and abnormal immune activation. Although highly
      active antiretroviral therapy regimens can increase circulating CD4 T lymphocyte
      counts and decrease the risk of opportunistic complications, the effects of these
      treatments on immune reconstitution are not well understood. In 44 persons with
      moderately advanced HIV-1 infection, after 12 weeks of treatment with zidovudine,
      lamivudine, and ritonavir, plasma HIV-1 RNA fell a median of 2.3 logs (P <
      .0001). Circulating numbers of naive and memory CD4 T lymphocytes (P < .001),
      naive CD8 T lymphocytes (P < .004), and B lymphocytes (P < .001) increased.
      Improved lymphocyte proliferation to certain antigens and a tendency to
      improvement in delayed-type hypersensitivity also were seen. Dysregulated immune
      activation was partially corrected by this regimen; however, the perturbed
      expression of T cell receptor V regions in the CD4 and CD8 T lymphocyte
      populations was not significantly affected. Ongoing studies will ascertain if
      longer durations of virus suppression will permit more complete immune
      restoration.

PMID- 9652426
TI  - Zidovudine treatment in patients with primary (acute) human immunodeficiency
      virus type 1 infection: a randomized, double-blind, placebo-controlled trial.
      DATRI 002 Study Group. Division of AIDS Treatment Research Initiative.
AB  - A multicenter, double-blind, placebo-controlled trial randomized 28 patients with
      primary (acute) human immunodeficiency virus (HIV)-1 infection (PHI) to receive
      zidovudine, 1000 mg daily, or placebo for 24 weeks. At week 48, compared with
      placebo patients, zidovudine-treated patients had significantly higher CD4 cell
      counts (zidovudine, 666 cells/mm3; placebo, 362; P = .004) and lower peripheral
      blood mononuclear cell (PBMC) culture titers (zidovudine, 0.58 log infectious
      units per million cells; placebo, 1.68; P = .02) but no difference in plasma RNA
      (zidovudine, 3.93 log copies/mL; placebo, 4.00; P = .83). Serious adverse events
      and minor clinical events were infrequent and comparable in both arms. There were
      two deaths: 1 patient died of sepsis and renal disease (zidovudine arm), and 1
      patient died of sepsis and tension pneumothorax (placebo arm). Six months of high
      dose zidovudine initiated during PHI results in higher CD4 cell counts and lower
      PBMC culture titers but no difference in plasma HIV-1 RNA. Further studies with
      more potent antiretroviral combination therapies are warranted.

PMID- 9652427
TI  - First human trial of a DNA-based vaccine for treatment of human immunodeficiency
      virus type 1 infection: safety and host response.
AB  - A DNA-based vaccine containing human immunodeficiency virus type 1 (HIV-1) env
      and rev genes was tested for safety and host immune response in 15 asymptomatic
      HIV-infected patients who were not using antiviral drugs and who had CD4+
      lymphocyte counts of > or = 500 per microliter of blood. Successive groups
      received three doses of vaccine (30, 100, or 300 microg) at 10-week intervals in
      a dose-escalation trial. Vaccine administration induced no local or systemic
      reactions, and no laboratory abnormalities were detected. Specifically, no
      patient developed anti-DNA antibody or muscle enzyme elevations. No consistent
      change occurred in CD4 or CD8 lymphocyte counts or in plasma HIV concentration.
      Antibody against gp120 increased in individual patients in the 100- and 300
      /microg groups. Some increases were noted in cytotoxic T lymphocyte activity
      against gp160-bearing targets and in lymphocyte proliferative activity. The
      safety and potential immunogenicity of an HIV-directed DNA-based vaccine was
      demonstrated, a finding that should encourage further studies.

PMID- 9652428
TI  - Association of human immunodeficiency virus (HIV) load early in life with disease
      progression among HIV-infected infants. New York City Perinatal HIV Transmission
      Collaborative Study Group.
AB  - The utility of RNA virus load to predict progression of human immunodeficiency
      virus (HIV)-1 disease was assessed in 89 HIV-1-infected children. Of 22 virus
      load values during week 1 of life, 17 were below the detection threshold.
      Geometric mean virus load increased to approximately 7 x 10(5) copies/mL by week
      4, was sustained throughout the first 6 months of life, and then declined to 1.6
      x 10(5) copies/mL during the third year. Samples from week 1 of life had little
      predictive value, but virus load during days 7-30 strongly predicted progression
      to CDC-3 classification or death (P = .024; risk ratio = 1.6), and virus load
      during months 2-3 predicted progression to CDC-C or death within the first 6
      months of life (P = .002, risk ratio = 11). Virus load was highly associated with
      imminent vulnerability to CDC-C or death (P = .002) during the first 18 months of
      life. Except for values from the first week of life, virus load at any age
      through 18 months is strongly associated with risk of HIV disease progression.

PMID- 9652429
TI  - Mortality in the first 2 years among infants born to human immunodeficiency virus
      infected women in Harare, Zimbabwe.
AB  - Transmission of human immunodeficiency virus (HIV) and mortality was studied
      among infants of infected women in Zimbabwe. Of 367 infants born to HIV-infected
      women, 72 (19.6%) died compared with 20 (5.4%) of 372 infants of uninfected women
      (P < .01). Infection by HIV DNA polymerase chain reaction among infants who
      survived >7 days and died within 2 years could be assessed in 87% (58/67) of
      infants of infected women and 83% (5/6) of infants of uninfected women;
      transmission occurred in 40 of 58 infants. Among 27 infected infants tested at
      birth, 19 (70%), 5 (19%), and 3 (11%) were apparently infected via in utero,
      intrapartum or early postpartum, and late postpartum transmission, respectively.
      The majority of HIV-infected infants who died in the first 2 years of life were
      likely to have acquired in utero infection.

PMID- 9652430
TI  - Trends in AIDS-related opportunistic infections among men who have sex with men
      and among injecting drug users, 1991-1996.
AB  - Incidence trends for the 13 most frequent AIDS-defining opportunistic infections
      (OIs) among men who have sex with men (MSM, n = 15,588) and injecting drug users
      (IDUs, n = 4475) were examined using data abstracted from medical records in >90
      hospitals and clinics in nine US cities during 1991-1996. Among MSM, the most
      frequent OIs were Mycobacterium avium complex (MAC) disease, Pneumocystis carinii
      pneumonia (PCP), and cytomegalovirus (CMV) retinitis; decreasing (P < or = .05)
      trends occurred for 11 OIs (MAC disease, PCP, CMV retinitis, Kaposi's sarcoma,
      esophageal candidiasis, CMV disease, extrapulmonary cryptococcosis, toxoplasmic
      encephalitis, tuberculosis, chronic herpes simplex, and disseminated
      histoplasmosis). Among IDUs, the most frequent OIs were PCP, MAC disease, and
      esophageal candidiasis; decreasing trends occurred for 5 OIs (PCP, esophageal
      candidiasis, tuberculosis, chronic herpes simplex, and chronic cryptosporidiosis)
      and an increase occurred in recurrent pneumonia. The differences in trends for
      MSM and IDUs may be due to differences in medical care and adherence to
      preventive medications.

PMID- 9652431
TI  - Initial (6-month) results of three-times-weekly azithromycin in treatment
      regimens for Mycobacterium avium complex lung disease in human immunodeficiency
      virus-negative patients.
AB  - Two consecutive, open, prospective trials of intermittent azithromycin (600 mg),
      usually given Monday, Wednesday, and Friday (TIW) for Mycobacterium avium complex
      (MAC) lung disease were initiated in human immunodeficiency virus-negative
      patients. Regimen A consisted of TIW azithromycin and daily ethambutol (15
      mg/kg/day), daily rifabutin (300 mg/day), and initial twice weekly (BIW)
      streptomycin. Regimen B consisted of TIW azithromycin, TIW ethambutol (25
      mg/kg/dose), TIW rifabutin (600 mg/dose), and initial BIW streptomycin. Of 19
      patients enrolled in regimen A who completed at least 6 months of therapy, 14
      (74%) had sputum samples become culture-negative. Of 39 patients enrolled in
      regimen B who completed at least 6 months of therapy, 24 (62%) had sputum
      conversion. These sputum conversion rates are comparable to previous rates at 6
      months in patients receiving daily clarithromycin- or azithromycin-containing
      regimens. No resistance to azithromycin emerged with either regimen. This is the
      first study to demonstrate the efficacy of intermittent administration of
      medication for MAC lung disease.

PMID- 9652432
TI  - Expression of chemokines and induction of rapid cell death in human blood
      neutrophils by Mycobacterium tuberculosis.
AB  - To elucidate the role of neutrophils in the early inflammatory response to
      mycobacterial infection, expression of chemokines interleukin (IL)-8 and
      macrophage inflammatory protein-1alpha (MIP-1alpha) was examined in human blood
      neutrophils in response to the lipopolysaccharide (LPS) of Escherichia coli,
      which induces acute inflammation, or to Mycobacterium tuberculosis or purified
      protein derivative (PPD), which induce chronic mycobacterial inflammation.
      Neutrophils stimulated with LPS, M. tuberculosis, or PPD expressed both IL-8 and
      MIP-1alpha. Expression of IL-8 and MIP-1alpha was lower after stimulation with M.
      tuberculosis or PPD than after stimulation with LPS, but the kinetics of
      expression did not differ significantly. In contrast, both M. tuberculosis and
      PPD with tumor necrosis factor-alpha induced neutrophils to undergo rapid cell
      death, which might remove neutrophils and activate macrophages at sites of
      mycobacterial inflammation. The findings suggest that neutrophils play important
      roles in the host defense against mycobacterial infection.

PMID- 9652433
TI  - Cellular immune responses to four doses of percutaneous bacille Calmette-Guerin
      in healthy adults.
AB  - To explore the hypothesis that low-dose immunization might induce preferential
      Th1 cell immunity, 76 adults were vaccinated with one of four doses of bacille
      Calmette-Guerin (BCG): The doses contained very low (1.6 x 10(5) cfu), low (3.2 x
      10(6) cfu), standard (1.6 x 10(8) cfu), or high (3.2 x 10(8) cfu) levels of BCG.
      Delayed-type hypersensitivity responses occurred 8 weeks after vaccination in 10%
      of persons given very low or low doses of BCG, compared with 95% and 100% of
      persons given standard or high doses, respectively. Lymphoproliferative
      responses, which were increased only for high-dose vaccinees, peaked 2 weeks
      after vaccination and were directed chiefly against Mycobacterium tuberculosis
      secreted proteins, particularly the antigen 85 complex. Significant increases in
      mycobacteria-specific interferon-gamma expression were present 16 weeks after
      vaccination only for persons given standard or high doses of BCG. Percutaneous
      BCG appears capable of inducing a temporary Th1-like immune response, but
      standard or higher dosages are required.

PMID- 9652434
TI  - Protein F1 is required for efficient entry of Streptococcus pyogenes into
      epithelial cells.
AB  - It was recently reported that strains of Streptococcus pyogenes are capable of
      inducing entry of the bacterium into epithelial cells; however, nothing is known
      regarding the gene(s) and the underlying mechanism(s) involved. Using isogenic
      mutants of S. pyogenes JRS4 strain that are defective in the expression of each
      of the surface proteins F1 and M6, it was demonstrated that both are required for
      efficient internalization. Expression of F1 on the surface of a poorly invading
      S. pyogenes strain significantly enhances its internalization efficiency. Protein
      F1-mediated internalization is inhibited by UR, the nonrepetitive fibronectin
      binding domain of this protein, and to a lesser extent, by the repetitive
      fibronectin-binding domain, RD2. Polyclonal anti-human fibronectin antibodies
      completely abolish F1-mediated internalization; increasing fibronectin
      concentrations result in a significant enhancement of bacterial uptake. The
      findings shown here suggest that protein F1 mediates streptococcal
      internalization and that the M6 protein is required for more efficient entry of
      the bacterium.

PMID- 9652435
TI  - Penicillin-binding protein 5 sequence alterations in clinical isolates of
      Enterococcus faecium with different levels of beta-lactam resistance.
AB  - The low-affinity penicillin-binding protein (PBP) 5 is the main beta-lactam
      target and is responsible for resistance to this class of antibiotics in
      Enterococcus faecium. The PBP 5 variants of 15 clinical isolates (including 8
      resistant to vancomycin) with different levels of beta-lactam resistance were
      analyzed. Most of the highly beta-lactam-resistant isolates produced small
      quantities of PBP 5 of low affinity. This was associated with particular amino
      acid substitutions: an Ala or Ile for Thr-499, a Glu for Val-629, and a Pro for
      Ser-667. A change of Met-485 to Thr or Ala (adjacent to the conserved SDN box)
      was observed in isolates with MICs of ampicillin of 64 or 128 microg/mL,
      respectively. In the 2 most resistant isolates, with MICs of ampicillin of 256
      microg/mL, an additional Ser was present just after Ser-466. Thus, particular
      point mutations in PBP 5 and combinations thereof may lead to high-level beta
      lactam resistance in E. faecium.

PMID- 9652436
TI  - Molecular epidemiology of methicillin-resistant Staphylococcus aureus in 12 New
      York hospitals. MRSA Collaborative Study Group.
AB  - Consecutive single-patient methicillin-resistant Staphylococcus aureus (MRSA)
      isolates (270) from 12 hospitals (8217 beds) in metropolitan New York City were
      collected during May 1996. In 11 of 12 hospitals, MRSA was most frequent in the
      general medical services. DNA typing ("fingerprinting") revealed that
      mecA:Tn554:PFGE (pulsed-field gel electrophoresis) type I:A:A accounted for 113
      (42%) of 270 isolates, was detected in all hospitals, and was the predominant
      clone in 9. Thirteen of 15 I:E:F isolates were from 1 hospital, and the remaining
      2 were from another hospital of the same health system. Type V:NH:E was isolated
      from 22 (79%) of the 28 patients with AIDS, including 8 of 9 patients from an
      additional hospital. Subtype V:NH:E2 was recovered from 11 patients, 9 of whom
      had AIDS, including all 5 AIDS patients from one floor of a nursing home
      affiliated with a third hospital. By using both mecA:Tn554 probes and PFGE, MRSA
      clusters and outbreaks may be detected and provide a rationale for appropriate
      infection control intervention.

PMID- 9652438
TI  - Induction of apoptosis in normal human renal tubular epithelial cells by
      Escherichia coli Shiga toxins 1 and 2.
AB  - The cytotoxicity of Shiga toxin (Stx) 1 and Stx2 produced by Escherichia coli to
      human renal cortical epithelial cells (HRCEC) in primary culture was
      investigated. HRCEC express CD24, the marker of renal distal tubules, as well as
      globotriaosyl ceramide/CD77, the receptor for Stxs. Binding of Stxs to HRCEC was
      confirmed by positive staining with specific antibodies to Stxs. Treatment of
      HRCEC with Stxs induced rapid cell death, which was reversed in the presence of
      neutralizing antibody specific for Stx. DNA fragmentation was found to be
      accompanied by Stx-mediated cell death in HRCEC, indicating that apoptosis was
      part of the process. These data and previous reports indicate that a variety of
      renal cell types, including tubular epithelial cells as well as glomerular
      capillary endothelial cells, may be targets for Stx-mediated apoptosis, which
      could contribute to the pathogenesis of hemolytic-uremic syndrome caused by Stx
      producing E. coli infection.

PMID- 9652437
TI  - A large outbreak of botulism: the hazardous baked potato.
AB  - In April 1994, the largest outbreak of botulism in the United States since 1978
      occurred in El Paso, Texas. Thirty persons were affected; 4 required mechanical
      ventilation. All ate food from a Greek restaurant. The attack rate among persons
      who ate a potato-based dip was 86% (19/22) compared with 6% (11/176) among
      persons who did not eat the dip (relative risk [RR] = 13.8; 95% confidence
      interval [CI], 7.6-25.1). The attack rate among persons who ate an eggplant-based
      dip was 67% (6/9) compared with 13% (241189) among persons who did not (RR = 5.2;
      95% CI, 2.9-9.5). Botulism toxin type A was detected from patients and in both
      dips. Toxin formation resulted from holding aluminum foil-wrapped baked potatoes
      at room temperature, apparently for several days, before they were used in the
      dips. Consumers should be informed of the potential hazards caused by holding
      foil-wrapped potatoes at ambient temperatures after cooking.

PMID- 9652439
TI  - Enteroaggregative Escherichia coli as a potential cause of diarrheal disease in
      adults infected with human immunodeficiency virus.
AB  - Stools of 68 human immunodeficiency virus (HIV)-infected adults with diarrhea and
      60 without diarrhea were examined for enteroaggregative Escherichia coli (EAggEc)
      by HeLa cell adherence assay. EAggEc were present in stools of 30 patients with
      and 18 without diarrhea (P = .05). CD4 cell counts of patients with EAggEc and
      diarrhea were significantly lower than those of patients with EAggEc without
      diarrhea (P = .02). There was no difference in the mean duration of diarrheal
      symptoms or in the number of stools per day between patients with EAggEc and
      those without. None of the EAggEc strains were positive by polymerase chain
      reaction for adherence fimbria, but 11 strains were positive for EAggEc heat
      stable toxin EAST/1. Of the EAggEc strains, 51% were resistant to trimethoprim
      sulfamethoxazole and 65% were resistant to ampicillin. EAggEc may be a pathogen
      in HIV-infected patients with diarrhea; HIV-infected patients with EAggEc appear
      to be more symptomatic when HIV disease is more advanced.

PMID- 9652440
TI  - Evaluation of an isogenic hemolysin-deficient mutant in the human model of
      Haemophilus ducreyi infection.
AB  - Haemophilus ducreyi causes the genital ulcerative disease chancroid. One putative
      virulence factor of H. ducreyi is a pore-forming hemolysin that displays toxicity
      against human fibroblasts and keratinocytes. In order to test the role of the
      hemolysin in pathogenesis, an isogenic hemolysin-deficient mutant was
      constructed, designated 35000HP-RSM1. The lipooligosaccharide, outer membrane
      protein patterns, and growth attributes of 35000HP-RSM1 were identical to its
      parent, 35000HP. Human subjects were challenged on the upper arm with the
      isogenic isolates in a double-blinded, randomized, escalating dose-response
      study. Pustules developed at a similar rate at sites inoculated with the mutant
      or parent. The cellular infiltrate and bacterial load in lesions were also
      similar. These results indicate the hemolysin does not play a role in pustule
      formation. Due to the limitations of this model, the role of the hemolysin at
      later stages of infection could not be determined.

PMID- 9652441
TI  - Protection against experimental intraabdominal sepsis by two polysaccharide
      immunomodulators.
AB  - Two immunomodulating polysaccharides, poly-(1-6)-beta-glucotriosyl-(1-3)-beta
      glucopyranose (PGG)-glucan and Bacteroides fragilis polysaccharide A (PS A), were
      evaluated for the prevention of mortality and abscess formation associated with
      experimental intraabdominal sepsis. Prophylactic treatment with a combination of
      these compounds significantly reduced mortality (8% vs. 44% in the saline-treated
      control group) and the incidence of abscesses (30% vs. 100% in the saline-treated
      control group) after challenge with rat cecal contents. These compounds were also
      effective when administered therapeutically after bacterial contamination of the
      peritoneal cavity. PS A treatment conferred long-term protection against abscess
      formation and resulted in significantly fewer total aerobes and anaerobes in the
      peritoneal fluid of animals challenged with cecal contents. These data
      demonstrate the usefulness of two immunomodulatory polysaccharides in preventing
      experimental intraabdominal sepsis in the absence of antimicrobial therapy and
      may represent a new adjunct to antibiotic regimens currently used to prevent
      clinical cases of this disease.

PMID- 9652442
TI  - Vacuolating toxin production in clinical isolates of Helicobacter pylori with
      different vacA genotypes.
AB  - A vacuolating cytotoxin encoded by vacA in Helicobacter pylori is known as a
      potential virulent determinant. The relationship between different vacA alleles,
      vacuolating ability, and H. pylori-related diseases was investigated. Genetic
      analysis of 119 isolates from Taiwanese patients revealed that 104 strains were
      s1a/m2, 13 strains were characterized as the s1a/m1T type, which was more
      homologous to the s1a/m1 strains, and 2 were characterized as the s1a/m1Tm2
      chimeric type. Production of high-grade cytotoxin among 11 strains with s1a/m1T
      was higher (72.7%) than among 66 strains with s1a/m2 (21.2%) (P < .01). Peptic
      ulcer occurred in 76.9% of 13 patients with s1a/m1T strains compared with 46.2%
      of 104 patients with s1a/m2 strains (P < .05). These results suggest that s1a/m1T
      strains are associated with increased cytotoxic activity and higher ulcer
      prevalence than are s1a/m2 strains.

PMID- 9652443
TI  - Acid-tolerance response in Helicobacter pylori and differences between cagA+ and
      cagA- strains.
AB  - Helicobacter pylori cagA transcription and translation are maximal at pH 6 in
      stationary phase. The aim of this study was to determine whether H. pylori has an
      acid-tolerance response and whether that response is related to CagA expression,
      by investigating whether preexposure to pH 5 or 6 improved survival of cells
      subsequently exposed to pH 3. Cell number was determined after broth growth,
      after exposure to pH 5, 6, or 7, and then after a 30-min exposure to pH 3 without
      urea. H. pylori cells preexposed to pH 6 or 5 survived pH 3 exposure 100-fold
      better than did cells preexposed to pH 7. Cells of cagA+ strains grown at pH 6
      for 48 h, which induced maximal CagA expression, were significantly more
      susceptible to pH 3 than were wild type cagA- strains or isogenic cagA-
      knockouts. Thus, H. pylori strains possess a urea-independent acid-tolerance
      response. Differential acid susceptibility may contribute to preferential
      colonization of particular H. pylori strains in specific mucus layer niches.

PMID- 9652444
TI  - Prevalence of vacuolating cytotoxin production and distribution of distinct vacA
      alleles in Helicobacter pylori from China.
AB  - Studies of Helicobacter pylori from the West have linked production of
      vacuolating cytotoxin and a particular signal sequence (s1a) allele of the
      underlying vacA gene to peptic ulcer disease (PUD). Among Chinese H. pylori, most
      isolates from both PUD and gastritis patients were toxigenic (35/46 and 29/35,
      respectively). Polymerase chain reaction and DNA sequencing showed that 95 of 96
      isolates carried vacA s1a alleles. In the mid-region, 78 of 96 isolates carried
      m2; 14 were m1-like but only 87% identical (DNA-level) to classical m1 and were
      designated m1b; the other 4 were unusual hybrids (m1b-type proximal, m2-type
      distal). Isolates with m1b and m1b-m2 alleles produced higher levels of
      vacuolating activity than did isolates with m2 alleles (P < .01). There was no
      association between any vacA allele and disease. These results suggest that the
      composition of H. pylori gene pools varies geographically and that other as-yet
      unknown polymorphic H. pylori genes are important in PUD.

PMID- 9652445
TI  - Genetic basis for protection against experimental vaginal candidiasis by
      peripheral immunization.
AB  - In these studies, significant protection against experimental vaginal candidiasis
      after a subcutaneous immunization with Candida albicans extract was achieved in
      BALB/c mice but not in C57BL/6 (B6) mice. Protection from vaginal candidiasis was
      transferred to naive BALB/c mice by a population of spleen cells derived from
      immunized BALB/c mice. Removal of CD3 or CD4 but not CD8 T cells before transfer
      completely abrogated resistance to vaginal candidiasis. Recombinant inbred (RI)
      strains of mice derived from BALB/c and B6 strains were used for mapping loci
      that might be responsible for regulating vaginal protection after subcutaneous
      immunization. Linkage analysis using microsatellite-based genome mapping in these
      RI strains revealed four candidate loci on chromosomes 3, 7, 8, and 18 that
      exhibit statistically significant linkage to the strain distribution pattern.
      These results may contribute to the understanding of host genetic factors
      controlling the immune response to vaginal infections.

PMID- 9652446
TI  - Recognition of Pneumocystis carinii antigens by local antibody-secreting cells
      following resolution of P. carinii pneumonia in mice.
AB  - To examine the repertoire of Pneumocystis carinii antigens recognized by antibody
      secreting B cells from tracheobronchial lymph nodes isolated immediately
      following recovery from P. carinii pneumonia, monoclonal antibodies (MAbs) were
      produced from these cells. In contrast to previous studies of systemic immunity,
      P. carinii gpA was not the immunodominant antigen recognized by these B cells.
      Forty-nine (91%) of 54 P. carinii-specific hybridoma culture supernatants reacted
      with P. carinii antigens other than gpA. Many of the resulting MAbs recognized a
      previously uncharacterized antigen expressed on the surface of both cysts and
      trophozoites. Western blotting using one of the cloned MAbs revealed reactivity
      with a broad range of antigenic material, with the most intense reactivity in the
      50- to 65-kDa region of the blot. The antigens identified by these MAbs merit
      further investigation regarding protective immunity to P. carinii because they
      were recognized by B cells in the context of recovery from P. carinii pneumonia.

PMID- 9652447
TI  - Molecular methods for the diagnosis of genital ulcer disease in a sexually
      transmitted disease clinic population in northern Thailand: predominance of
      herpes simplex virus infection.
AB  - A multiplex polymerase chain reaction (M-PCR) assay that simultaneously detects
      the three major causes of genital ulcer disease (GUD), Haemophilus ducreyi,
      Treponema pallidum, and herpes simplex virus, was used to evaluate swab specimens
      for 38 sequential patients with GUD at a Thai sexually transmitted disease
      clinic. Subjects received clinical diagnoses and syndromic treatment. Swab
      specimens for H. ducreyi cultures and M-PCR were obtained. No H. ducreyi cultures
      were positive. Of 38 M-PCR specimens, 31 (81.6%) were positive for HSV, 1 (2.3%)
      for both HSV and T. pallidum, and none for H. ducreyi or T. pallidum alone; 6
      (15.8%) were negative for all 3 pathogens. Clinical diagnoses corresponded poorly
      to M-PCR findings; none of 5 suspected cases of chancroid were positive by M-PCR
      and none of 1 for syphilis, but 21 of 24 suspected herpes lesions were confirmed
      by M-PCR. Human immunodeficiency virus infection status was known for 24 of 38
      subjects; 11 (45.8%) were seropositive, and all 11 had HSV by M-PCR. HSV appeared
      to be the most common pathogen overall.

PMID- 9652448
TI  - Induction of interleukin-12 production in chronic hepatitis C virus infection
      correlates with the hepatocellular damage.
AB  - Interleukin (IL)-12 plays an essential role in host defense against infectious
      diseases. Serum IL-12 concentration and blood mononuclear cell production with or
      without specific interferon (IFN)-gamma priming were investigated in 65 chronic
      hepatitis C virus (HCV) patients and 25 healthy donors. HCV patients had higher
      serum IL-12 levels (P = .004) and produced higher amounts after IFN-gamma priming
      (P < .001) than donors. A subset of patients did not produce IL-12: They had
      lower serum levels (P = .032) and showed signs of liver piecemeal necrosis less
      frequently (P = .011). Patients with greater liver necroinflammatory activity
      produced more IL-12 than patients with minimal or mild activity and donors (P <
      .01). During IFN-alpha therapy for 16 HCV patients, individuals with end-of
      treatment alanine aminotransferase normalization and clearance of viremia had
      higher serum levels and produced more IL-12 than those who did not (P < .05).
      These results suggest a role for IL-12 in the immunopathogenesis and outcome of
      HCV infection.

PMID- 9652449
TI  - Association of rare human papillomavirus types with genital premalignant and
      malignant lesions.
AB  - Due to the limited number of reports concerning their association with particular
      dysplastic and neoplastic lesions, the oncogenic potential of so-called rare or
      novel human papillomavirus (HPV) types is still unclear. Cytologic smears or
      biopsy specimens from 538 patients were analyzed for dysplastic or neoplastic
      lesions and HPV infection. The HPV detection and typing system utilized allowed
      identification of all mucosal HPVs amplifiable by L1 polymerase chain reaction.
      Considering only patients infected with a single HPV type (n = 329), rare or
      novel HPVs (HPV-59, HPV-61, HPV-62, HPV-66, HPV-70, HPV-73, MM4, MM7, MM8,
      CP6108, and CP8304) were detected in 28% of normal specimens (n = 46), none of
      condylomatous lesions (n = 44), 12% of low-grade squamous intraepithelial lesions
      (SILs) (n = 42), 8% of high-grade SILs (n = 142), and 4% of cervical cancers (n =
      54). Prevalence and oncogenic potential of distinct rare HPV types seems to be
      higher than previously assumed.

PMID- 9652450
TI  - No evidence for persistent enterovirus infection in patients with end-stage
      idiopathic dilated cardiomyopathy.
AB  - Persistence of enteroviruses in heart tissue has been implicated in the etiology
      of idiopathic dilated cardiomyopathy (IDC). Therefore, we determined the
      prevalence of enterovirus RNA in heart tissue from patients with end-stage IDC.
      During heart transplantation, 287 transmural biopsy specimens were aseptically
      collected from the explanted hearts of 38 patients with IDC and of 39 patients
      with cardiac failure of known cause. A nested polymerase chain reaction with
      general specificity for enteroviruses was used to screen for the presence of
      enterovirus RNA in the heart tissue samples. No enterovirus RNA was detected in
      any of the 287 heart biopsy specimens. These findings lead to a conclusion that
      enteroviruses do not persist in heart tissue from patients with end-stage IDC,
      nor with other heart diseases of known cause.

PMID- 9652452
TI  - Disco fever: epidemic meningococcal disease in northeastern Argentina associated
      with disco patronage.
AB  - Neisseria meningitidis is a leading cause of adult meningitis worldwide. From 5
      to 14 August 1996, 8 cases of meningococcal disease occurred in Corrientes city
      (population 306,000) in northeastern Argentina. Those infected ranged in age from
      15 to 45 years (median, 18.5). To determine risk factors for infection, a case
      control study was done. Infecting isolates were serogrouped and underwent
      phenotyping by multilocus enzyme electrophoresis (MLEE) and pulsed-field gel
      electrophoresis (PFGE). Those infected were significantly more likely than those
      not infected to have had exposure to passive or active cigarette smoke or to have
      attended a particular disco. Isolates available from 6 case-patients were all
      serogroup C; all had identical MLEE and PFGE patterns. These data suggest that
      dance clubs or discos may be a focus of transmission of N. meningitidis among
      young people.

PMID- 9652451
TI  - Quantification of CD8+ T lymphocytes responsive to human immunodeficiency virus
      (HIV) peptide antigens in HIV-infected patients and seronegative persons at high
      risk for recent HIV exposure.
AB  - The combination of a tumor necrosis factor (TNF)-alpha enzyme-linked immunospot
      (ELISPOT) assay and computer-assisted video image analysis was used to detect and
      quantitate in peripheral blood CD8+ T cells reactive with known human
      immunodeficiency virus type 1 (HIV-1) peptide antigens presented by HLA-A2 or HLA
      A3. T lymphocyte responsiveness to at least one HIV peptide was found in 10 (83%)
      of 12 HIV-1-infected patients and in 5 (45%) of 11 persons who had no serologic
      and virologic signs of HIV infection but who were at high risk for recent sexual
      exposure to HIV-1. CD8+ T cells responding to HIV-1 peptides were observed in
      none of 11 HIV-seronegative donors without a history of HIV exposure. ELISPOT
      assays are relatively fast and easy to perform and appear to reliably detect T
      cell reactivity due to previous exposure to HIV. These findings support the use
      of the ELISPOT assay for monitoring T cell responsiveness to HIV peptides.

PMID- 9652453
TI  - Circulating endotoxin during initial antibiotic treatment of severe gram-negative
      bacteremic infections.
AB  - The impact of antibiotics on total endotoxemia and circulating tumor necrosis
      factor (TNF)-alpha, interleukin (IL)-6, and IL-8 in 18 patients with severe
      bacteremic sepsis or septic shock due to gram-negative species was investigated.
      Endotoxemia, TNF-alpha, IL-6, and IL-8 were assayed before (H0) and 1 h (H1) and
      4 h (H4) after the first antibiotic infusion. Endotoxemia decreased from H0
      (median, 0.4 EU/mL; interquartile interval, 0.09-1.23) to H1 (median, 0.19 EU/mL;
      interquartile interval, 0.07-0.75; P = .03) and remained stable between H1 and H4
      (median, 0.12 EU/mL; interquartile interval, 0.09-0.30; P = .4). IL-6 levels fell
      between H0 and H4 (P = .01) and between H1 and H4 (P = .03). IL-8 was higher at
      H0 than at H1 (P = .04) and at H4 (P = .01). These results suggest that
      endotoxemia is not increased by antibiotherapy of severe gram-negative
      bacteremia.

PMID- 9652455
TI  - A guinea pig model for Q fever endocarditis.
AB  - A new model of experimental endocarditis, using electrocoagulation of native
      aortic valves, was used for the study of Q fever endocarditis. In the 20 guinea
      pigs electrocoagulated and inoculated with Coxiella burnetii Nine Mile phase I
      strain, 10 presented with infective endocarditis. Of these, 7 died spontaneously.
      All guinea pigs with endocarditis presented with blood cultures positive for C.
      burnetii, and C. burnetii antigen was found in their cardiac valves. Positive
      blood cultures or valvular immunopositive cells were not identified in either
      nonelectrocoagulated or noninoculated controls. This experimental model
      demonstrates that Q fever in an animal with previously damaged valves results in
      endocarditis. It could provide a new tool for the investigation of
      pathophysiology and antibiotic therapy for Q fever endocarditis.

PMID- 9652454
TI  - High prevalence of Chlamydia pneumoniae DNA in peripheral blood mononuclear cells
      in patients with cardiovascular disease and in middle-aged blood donors.
AB  - Nested polymerase chain reaction (nPCR) demonstrated the presence of Chlamydia
      pneumoniae-specific DNA in peripheral blood mononuclear cells (PBMC). PBMC
      samples were obtained from 103 consecutive patients (62 male, 41 female) aged 22
      85 years (mean, 64) admitted for coronary angiography because of suspected
      coronary heart disease and from 52 blood donors (43 male, 9 female) aged 40-64
      years (mean, 49). Of the 101 evaluable patients, 60 (59%) were identified by nPCR
      assay as C. pneumoniae DNA carriers; C. pneumoniae-specific
      microimmunofluorescence (MIF) serology confirmed exposure to the bacterium in 57
      (95%) of the 60 nPCR-positive patients. Among the 52 blood donors, the nPCR assay
      identified 24 (46%) C. pneumoniae DNA carriers, all of whom were positive by C.
      pneumoniae-specific serology. Thirty-two patients (32%) and 23 blood donors (44%)
      were MIF antibody-positive but repeatedly nPCR-negative; Bartonella henselae- or
      Bartonella quintana-specific antibodies were not detected among any of these
      subjects. In this study, C. pneumoniae DNA was common in PBMC of patients with
      coronary heart disease and in middle-aged blood donors.

PMID- 9652456
TI  - Detection of Onchocerca volvulus infection by O-150 polymerase chain reaction
      analysis of skin scratches.
AB  - The standard assay for onchocerciasis diagnosis is microscopic detection of
      parasites in skin snips. Skin snipping is painful and may potentially transmit
      bloodborne infections. Thus, an alternative method for the diagnosis of
      onchocerciasis that does not require skin snipping is needed. A polymerase chain
      reaction (PCR)-based assay was shown to detect the presence of parasite DNA in
      superficial skin scrapings. Detection of parasite DNA in both skin snips and skin
      scratches was found to be more sensitive for detecting low-density infections
      than was microscopic examination of skin snips. The skin scratch PCR assay is
      minimally invasive and painless and does not present the risk of transmitting
      bloodborne infections. These properties make the skin scratch an attractive
      alternative to the skin snip for detecting O. volvulus infection.

PMID- 9652457
TI  - Humoral immune responses of Africans to cysteine protease-related antigens of
      Plasmodium falciparum.
AB  - The Plasmodium falciparum serine repeat antigen (SERA) and serine repeat protein
      homologue (SERPH) contain highly conserved domains that appear to encode cysteine
      proteases or related proteins. Humoral immune responses against the protease
      domains of SERA and SERPH were evaluated. Malaria-immune Africans, but not
      nonimmune controls, demonstrated potent humoral responses against the protease
      domains. As the SERA and SERPH protease domains are likely accessible to
      circulating antibody, these results suggest that humoral responses to the domains
      may contribute to antimalarial immunity.

PMID- 9652458
TI  - Chemotherapy accelerates the development of acquired immune responses to
      Schistosoma haematobium infection.
AB  - Treatment of 41 Schistosoma haematobium-infected children, 5-16 years old, with
      the drug praziquantel induced a switch from a predominantly IgA-specific antibody
      response to a predominantly IgG1 response within 12 weeks. A cross-sectional
      survey suggests that the same switch occurs naturally, but over several years, as
      children age (n = 251). The switch may be driven by alterations in cytokine
      levels in response to the release of antigens by dead or damaged parasites.
      Adults are more resistant to schistosome infection than children, and the switch
      to an "adult" response suggests that praziquantel treatment may have an
      immunizing effect, with benefits extending beyond a transient reduction in levels
      of infection.

PMID- 9652459
TI  - False-negative fluorescent treponemal tests and confirmation of syphilis
      infection.

PMID- 9652460
TI  - Presidential address: the Yorpy principle.

PMID- 9652461
TI  - Initial experience with endovascular aneurysm repair: comparison of early results
      with outcome of conventional open repair.
AB  - PURPOSE: To determine the safety, effectiveness, and problems encountered with
      endovascular repair of abdominal aortic aneurysm (AAA). Initial experience with
      endoluminal stent grafts was examined and compared with outcome for a matched
      concurrent control group undergoing conventional operative repair of AAA.
      METHODS: Over a 3-year period, 30 patients underwent attempts at endovascular
      repair of infrarenal AAA. Of the 28 (93%) successfully implanted endografts, 8
      were tube endografts, 8 bifurcated grafts, and 12 aortouniiliac grafts combined
      with femorofemoral bypass. Most of the procedures were performed in the past year
      because the availability of bifurcated and aortoiliac endografts markedly
      expanded the percentage of patients with AAA who might be treated with
      endoluminal methods. The follow-up period ranged from 1 to 44 months, with a mean
      value of 11 months. RESULTS: Endovascular procedures demonstrated significant
      advantages with respect to reduced blood loss (408 versus 1287 ml), use of an
      intensive care unit (0.1 versus 1.75 days), length of hospitalization (3.9 versus
      10.3 days), and quicker recovery (11 versus 47 days). Although the total number
      of postoperative complications was identical for the two groups, the nature of
      the complications differed considerably. Local and vascular complications
      characteristic of endovascular repair could frequently be corrected at the time
      of the procedure and tended to be less severe than systemic or remote
      complications, which predominated among the open surgical repair group. On an
      intent-to-treat basis, 23 (77%) of the 30 AAAs were successfully managed with
      endoluminal repair. The seven (23%) failures were attributable to two immediate
      conversions caused by access problems, three persistent endoleaks, one late
      conversion caused by AAA expansion, and one late rupture. CONCLUSIONS: Although
      less definitive than those for conventional operations, these early results
      suggest that endovascular AAA repair offers considerable benefits for appropriate
      patients. The results justify continued application of this method of AAA repair,
      particularly in the treatment of older persons at high risk.

PMID- 9652462
TI  - Penetrating ulcer of the thoracic aorta: what is it? How do we recognize it? How
      do we manage it?
AB  - BACKGROUND: Although classic type A and B aortic dissections have been well
      described, less is known about the natural history of penetrating atherosclerotic
      ulcers of the thoracic aorta. This study differentiates penetrating ulcer from
      aortic dissection, determines the clinical features and natural history of these
      ulcers, and establishes appropriate correlates regarding optimal treatment.
      METHODS: A retrospective review of patient records and imaging studies was
      conducted with 198 patients with initial diagnoses of aortic dissection (86 type
      A, 112 type B) at our institution from 1985 to 1997. RESULTS: Of the 198
      patients, 15 (7.6%) were found to have a penetrating aortic ulcer on re-review of
      computed tomographic scans, magnetic resonance images, angiograms,
      echocardiograms, intraoperative findings, or pathology reports. Two ulcers
      (13.3%) were located in the ascending aorta; the other 13 (86.7%) were in the
      descending aorta. In comparison with those with type A or B aortic dissection,
      patients with penetrating ulcer were older (mean age 76.6 years, p = 0.018); had
      larger aortic diameters (mean diameter 6.5 cm); had ulcers primarily in the
      descending aorta (13 of 15 patients, 86.7%); and more often had ulcers associated
      with a prior diagnosed or managed AAA (6 of 15 patients, 40.0%; p = 0.0001). Risk
      for aortic rupture was higher among patients with penetrating ulcers (40.0%) than
      patients with type A (7.0%) or type B (3.6%) aortic dissection (p = 0.0001).
      CONCLUSIONS: Accurate recognition and differentiation of penetrating ulcers from
      classic aortic dissection at initial presentation is critical for optimal
      treatment of these patients. For penetrating ulcer, the prognosis may be more
      serious than with classic type A or B aortic dissection. Surgical management is
      advocated for penetrating ulcers in the ascending aorta and for penetrating
      ulcers in the descending aorta that exhibit early clinical or radiologic signs of
      deterioration.

PMID- 9652463
TI  - Carotid endarterectomy after NASCET and ACAS: a statewide study. North American
      Symptomatic Carotid Endarterectomy Trial. Asymptomatic Carotid Artery Stenosis
      Study.
AB  - PURPOSE: Since the North American Symptomatic Carotid Endarterectomy Trial
      (NASCET) and the Asymptomatic Carotid Artery Stenosis Study (ACAS) established
      the efficacy of carotid endarterectomy at large academic centers, there have been
      two community-based studies of outcomes after this operation. The purpose of this
      study was to perform a statewide survey to evaluate postoperative morbidity and
      mortality after carotid endarterectomy among patients throughout Maine. METHODS:
      A statewide registry was established to collect prospective data on carotid
      operations from January 1 to December 31, 1995. All surgeons and hospitals in the
      state were solicited to participate. All carotid endarterectomies were intended
      to be included; the only exclusion criterion was out-of-state residence.
      Comorbidities, preoperative studies, surgical indications, operative technique,
      and postoperative outcomes were analyzed. State administrative data were used to
      assess registry coverage. RESULTS: Ten of 17 hospitals participated, and 58% of
      all carotid endarterectomies performed in the state were included. Three hundred
      sixty-four operations were entered into the registry. Forty-four percent of the
      operations were performed for transient ischemic attack, 37% for asymptomatic
      stenosis, and 19% for stroke. The postoperative stroke rate was 2.5% with a total
      neurologic complication rate of 4.7% (transient ischemic attack and stroke).
      There was one postoperative death (mortality rate 0.3%). Patients with symptoms
      had a higher incidence of postoperative stroke (4.0% vs 0% asymptomatic; p <
      0.05) and transient ischemic attacks (3.8% vs 0.8% asymptomatic). Hospital stroke
      rates varied from 0% to 7%. Stroke rate did not differ significantly between low
      volume hospitals (2 to 28 patients/year, 3.3%) and high-volume hospitals (29 to
      101 patients/year, 2.3%) or between low-volume surgeons (fewer than 11
      operations/year, 1.7%) and high-volume surgeons (more than 12 operations/year,
      2.4%). Among 26 reporting surgeons, stroke rate varied from 0% to 10%; the
      absolute number of strokes per surgeon varied between zero and two. CONCLUSION:
      The statewide registry showed a postoperative stroke plus death rate of 2.8%,
      comparable with the NASCET and ACAS findings. Although this study had inherent
      limitations, the results from one state, including a variety of community
      practices, achieved results comparable with those of landmark trials.

PMID- 9652464
TI  - Cerebral microembolism and ischemic changes associated with carotid
      endarterectomy.
AB  - PURPOSE: The purpose of this study is to characterize microembolic signals (MS)
      that occur during the various phases of carotid endarterectomy (CEA) and to
      consider their relationship to postoperative changes on magnetic resonance
      imaging (MRI). METHODS: This was a retrospective study of 76 patients who
      underwent 78 carotid endarterectomies at a referral center. Perioperative
      transcranial Doppler monitoring and MRI were performed before and after CEA. The
      types of MS that occurred during phases of surgery were analyzed and compared
      with MRI changes. RESULTS: We observed a clinical stroke in one patient (1.3%)
      and ipsilateral small areas of silent ischemic change on seven postoperative MRI
      studies (9.0%). In 95% of CEAs, MS were detected. Only those MS observed in the
      recovery room that occurred at a rate of more than five per 15 minutes were
      associated with postoperative MRI ischemic changes (p < 0.0001). CONCLUSIONS:
      Ischemic changes on MRI after CEA are related to postoperative MS.

PMID- 9652465
TI  - Percutaneous ultrasound guided thrombin injection: a new method for treating
      postcatheterization femoral pseudoaneurysms.
AB  - PURPOSE: Since its introduction in 1991, ultrasound guided compression repair of
      postcatheterization femoral artery pseudoaneurysms has been shown to be
      effective. Disadvantages of ultrasound guided compression repair include patient
      discomfort during compression, inability to treat noncompressible
      pseudoaneurysms, prolonged use of ultrasound equipment and personnel, limited
      success with patients being treated with anticoagulants, and some early
      recurrences. We conducted a prospective study to evaluate a new method of
      treating femoral pseudoaneurysms, percutaneous ultrasound guided thrombin
      injection. METHODS: Under duplex ultrasound guidance, a 22- or 25-gauge needle
      was percutaneously positioned within the pseudoaneurysm. Without compressing the
      pseudoaneurysm, 0.5 to 1 ml thrombin solution (1000 U/ml) was injected to induce
      thrombosis. Early in the study, the procedure was modified to allow more than one
      injection. After successful thrombosis, the patients were kept at rest in bed for
      at least 1 hour. Duplex ultrasound examination was repeated in 1 to 4 days.
      Distal pulses and ankle-brachial indexes were measured before and after the
      procedure. RESULTS: Twenty of 21 consecutive pseudoaneurysms were successfully
      treated with thrombin injection. Fifteen pseudoaneurysms thrombosed immediately
      (<20 seconds) after one injection. The other five had partial thrombosis after
      one injection and complete thrombosis immediately after a second injection. The
      one failure occurred in a patient who had only one injection and then underwent
      subsequent ultrasound guided compression repair, which failed. No patient
      required sedation or analgesia during thrombin injection. There were no procedure
      related complications and no recurrences. CONCLUSIONS: Percutaneous ultrasound
      guided thrombin injection appears to be a safe and expeditious method for
      treating postcatheterization femoral pseudoaneurysms. It has significant
      advantages with respect to ultrasound guided compression repair or surgical
      repair.

PMID- 9652466
TI  - Fate of the contralateral leg after infrainguinal bypass.
AB  - PURPOSE: To identify variables predictive of the need for future vascular
      intervention in a leg contralateral to one currently undergoing infrainguinal
      bypass. METHODS: We reviewed the records of 450 consecutively treated patients
      undergoing infrainguinal bypass for occlusive disease to examine the outcome of a
      previously untreated contralateral leg. Patients with coexistent contralateral
      limb-threatening ischemia at the time of initial ipsilateral operation were
      excluded, as were patients with bilateral disease who underwent a staged
      contralateral procedure within 3 months of the ipsilateral operation. This
      yielded a study cohort of 383 patients with no anticipated intervention in the
      contralateral leg who were followed for a mean value of 38 months. Patient
      survival and subsequent intervention in the contralateral leg were examined with
      life-table and regression analysis. RESULTS: Mean age of the patients was 68
      years; 60% were men; 54% had diabetes; and 50% had coronary artery disease. The
      initial ipsilateral operation was performed for limb threat in 90% of instances.
      Twenty percent of patients subsequently needed intervention in the contralateral
      leg (infrainguinal bypass 83%, primary major amputation 17%). According to life
      table analysis, 30% of patients needed intervention at 5 years, and the overall
      survival rate was 51% at 5 years. Multivariate analysis indicated that the need
      for future contralateral intervention was independently predicted with the
      following four risk factors: diabetes (relative risk [RR] 2.4x), coronary artery
      disease (RR 1.8x), lower initial ankle-brachial index (RR 2.1x with ankle
      brachial index less than 0.7), and younger age (RR 2.2x if age less than 70
      years). Regression models predicted the need for contralateral intervention for
      only 8% of patients at 5 years when none of these risk factors was present but
      for 67% when all risk factors were present. CONCLUSION: The fate of the
      contralateral leg after infrainguinal bypass is affected by diabetes, coronary
      artery disease, contralateral ankle-brachial index, and age at initial
      ipsilateral bypass. The effect of these risk factors is additive in prediction of
      the likelihood of future intervention. Knowledge of these factors may help
      identify instances in which the contralateral greater saphenous vein will be
      important for future limb salvage and also determine which patients need more
      careful follow-up care.

PMID- 9652467
TI  - Early outcome of in situ femorotibial reconstruction among patients with diabetes
      alone versus diabetes and end-stage renal failure: analysis of 83 limbs.
AB  - PURPOSE: Both end-stage renal disease and diabetes have been demonstrated to have
      a negative effect on the outcome of infrainguinal arterial reconstruction,
      primarily because of increased perioperative morbidity and wound complications.
      This study was undertaken to determine whether the combination of these comorbid
      factors affects the outcome of distal arterial reconstruction. METHODS: Eighty
      three distal lower extremity arterial bypasses originating from the femoral
      artery and terminating at the peroneal, anterior, or posterior tibial artery were
      performed on 76 patients over a 5-year period at a tertiary care medical center.
      Autogenous greater saphenous vein was used as the bypass conduit in all
      instances. Combined inflow and composite vein procedures were excluded. RESULTS:
      There was one perioperative death, for a mortality rate of 1.2%. The diabetes
      mellitus (DM) plus end-stage renal disease (DM+ESRD) cohort displayed a
      significantly lower 1-year primary patency rate compared with the diabetes
      mellitus cohort, 53% versus 82% (p < 0.02). However, the limb salvage rate for
      the DM+ESRD and DM cohorts during the same time interval were not significantly
      different, 63% versus 84% (p < 0.06). The 52% 1-year survival rate for the
      DM+ESRD cohort was strikingly lower than the 90% 1-year survival rate for the DM
      cohort (p < 0.002). CONCLUSION: Despite the use of the optimal autogenous
      conduit, the combination of diabetes and end-stage renal disease can be expected
      to significantly decrease primary graft patency without affecting limb salvage.
      The greatest effect of these comorbid factors is on patient survival.

PMID- 9652468
TI  - Impact of a critical pathway on postoperative length of stay and outcomes after
      infrainguinal bypass.
AB  - PURPOSE: To determine the effect of a critical pathway on postoperative length of
      stay and outcomes after infrainguinal bypass. METHODS: A critical pathway for
      care of patients after infrainguinal bypass was introduced in December 1995 to
      coordinate postoperative care at our institution. We compared care of 67
      consecutively treated patients before institution of the pathway with care of 69
      consecutively treated patients with the critical pathway in place. Data
      collection was done by means of chart review. Univariate analyses were used to
      identify differences between prepathway and postpathway patients and to identify
      factors influencing postoperative length of stay. Multivariate analysis was used
      to identify factors that influenced length of stay and to examine the effect of
      use of the pathway after adjusting for other factors. RESULTS: Patients on the
      pathway were similar to prepathway controls with respect to comorbid illnesses,
      vascular risk factors, indications for surgical treatment, type of conduit, and
      type of operation. Factors associated with longer postoperative stays included
      distal anastomoses to tibial rather than popliteal vessels (p = 0.02),
      preexisting cardiac disease (p = 0.005), postoperative complications (p =
      0.0003), lower preoperative hematocrit (p = 0.01), and elevated preoperative
      creatinine level (p = 0.006). Overall, pathway patients had somewhat shorter
      postoperative lengths of stay (median value 7 days; range 2 to 29 days) than
      prepathway patients (median value 6 days; range 2 to 35; p = 0.01), and the two
      groups had similar frequencies of postoperative complications, readmission, and 6
      month mortality. However, patients on the pathway were more likely to be
      discharged to an intermediate-care facility rather than directly home. After 12
      patients with extraordinarily prolonged postoperative stays were excluded,
      multivariate analysis indicated that pathway patients had significantly shorter
      postoperative stays (p = 0.001). However, the difference was not significant if
      patients with extraordinarily long postoperative stays were included in the
      analysis (p = 0.28). CONCLUSION: Use of a critical pathway was associated with a
      modest decrease in postoperative length of stay for most patients. This was
      accomplished without an adverse effect on readmission, complication, or mortality
      rates. However, the decrease in stay may have been achieved primarily by
      discharging more patients to intermediate-care facilities. The pathway did not
      appear to have any effect when the subset of patients with extraordinarily long
      stays because of complex medical problems was included.

PMID- 9652469
TI  - Reduction of hospital resources utilization in vascular surgery: a four-year
      experience.
AB  - PURPOSE: Managed care whether through risk or through capitated contracts results
      in reduction in resources, reduced length of hospital stay, and reduced
      utilization of hospital resources (collectively referred to as resource
      reductions). These resource reductions will become even more noticeable as a
      greater proportion of Medicare patients who need vascular operations select a
      managed-care senior product. We examined the results of a 4-year experience with
      resource management in an academic vascular surgery practice during which best
      practice plans were developed and implemented. METHODS: We analyzed hospital cost
      data, which included both total hospital and intensive care unit length of stay,
      average units per operation for laboratory, pharmacy, and radiology services and
      operating room and direct hospital costs for 257 carotid endarterectomies
      performed over fiscal years (FY) 1994, 1995, 1996, and 1997 (6 month data) and
      175 infrainguinal bypass procedures performed during the same period. RESULTS:
      For carotid endarterectomy, length of stay decreased 66% over the 4-year period
      to an average of 2.07 days in FY97. Both radiology and pharmacy utilization were
      reduced after the first year of institution of best practice plans (56% and 32%
      respectively) with 4-year total reductions of 86% and 55% by FY97. The most
      notable changes included elimination of routine postoperative laboratory testing,
      use of aspirin rather than low-molecular-weight dextran, emphasis on oral rather
      than intravenous vasoactive drugs, and routine use of duplex scanning alone
      rather than angiography for diagnosis after FY94-95. The length of operating room
      time for carotid endarterectomy remained relatively constant from FY94 to FY97.
      As a result of these multiple factors, our study showed a 30% decrease in total
      average direct hospital costs for carotid endarterectomy from $9974 to $7002 in
      this 4-year period. Infrainguinal bypass graft procedures showed a progressive
      decrease in total cost of 28% for patients without complications to $15,186 but
      remained unchanged for those with complications. Laboratory use, pharmacy use,
      and radiology use were not significantly different. CONCLUSIONS: Case management
      for patients undergoing carotid endarterectomy and infrainguinal bypass grafting
      involving an integrated team of vascular surgeons, surgical house staff, a
      dedicated vascular nurse, and a social work case manager resulted in dramatic
      reductions both in length of stay and hospital resource utilization. As these
      costs decreased, operating room expenses assumed increasing importance. Operating
      room costs account for 60% of the direct costs of carotid endarterectomy and a
      comparable percentage for uncomplicated infrainguinal bypass grafting. Further
      substantial reductions in direct hospital costs will depend primarily on
      reductions in operating room costs, particularly those related to length of time
      in the operating room.

PMID- 9652470
TI  - Mesenteric and celiac duplex scanning: a validation study.
AB  - PURPOSE: To validate the accuracy of previously established duplex ultrasound
      criteria for > or =50% superior mesenteric artery (SMA) and celiac artery (CA)
      stenosis by comparison with arteriography. METHODS: Duplex criteria established
      retrospectively in our laboratory in 1991 identified an end-diastolic velocity
      (EDV) > or =45 cm/sec, or no flow signal, as highly sensitive (100%) and specific
      (92%) indicators for SMA stenosis > or =50% or occlusion. EDV was more accurate
      (95%) than peak systolic velocity (PSV), which had a maximal accuracy of 86% at a
      PSV > or =300 cm/sec, with low sensitivity (62%), but high specificity (100%).
      For CA, accurate velocity thresholds were not identified, but we subsequently
      noted that retrograde common hepatic artery flow direction from SMA collateral
      was highly predictive of severe CA stenosis or occlusion. Since publication of
      those findings, 243 mesenteric duplex scans were performed for clinical
      evaluation of suspected chronic mesenteric ischemia. Angiographic confirmation
      was available for a subset of 46. SMA and CA diameters were measured on lateral
      aortograms by observers blinded to the duplex results, and the original duplex
      diagnostic criteria were tested for accuracy. In addition, receiver operator
      characteristic curve analysis was performed on the velocity data to identify the
      most accurate velocity thresholds in the new data. RESULTS: Duplex was
      technically adequate in 98% of SMA, 96% of CA, and 89% of hepatic arteries, and
      arteriograms were adequate in 100% of SMA and 98% of CA. For the SMA, EDV > or
      =45 cm/sec again provided the best sensitivity (90%), specificity (91%), positive
      predictive value (90%), negative predictive value (91%), and overall accuracy
      (91%). As in the retrospective study, PSV > or =300 cm/sec provided low overall
      accuracy (81%), low sensitivity (60%), but high specificity (100%). Lowering the
      PSV threshold improved sensitivity but reduced accuracy. For CA, retrograde
      common hepatic artery flow direction was 100% predictive of severe CA stenosis or
      occlusion. Velocity data in CA provided accuracy not found in the original study.
      EDV > or =55 cm/sec or no flow signal had best overall accuracy (95%) with high
      sensitivity (93%) and specificity (100%). PSV > or =200 cm/sec or no signal also
      had excellent accuracy (93%), sensitivity (93%), and specificity (94%). In
      addition, three of four anatomic anomalies were correctly identified by duplex.
      These included one right hepatic and one common hepatic artery originating from
      the SMA, and one common celiacomesenteric trunk. CONCLUSION: This validation
      analysis confirms that duplex velocity criteria are accurate in the
      identification of mesenteric occlusive disease. Retrograde common hepatic artery
      flow direction correctly predicts severe CA stenosis or occlusion. Duplex
      ultrasound may also identify mesenteric anatomic variants that can influence
      study interpretation.

PMID- 9652471
TI  - Telemedicine in vascular surgery: feasibility of digital imaging for remote
      management of wounds.
AB  - PURPOSE: Telemedicine coupled with digital photography could potentially improve
      the quality of outpatient wound care and decrease medical cost by allowing home
      care nurses to electronically transmit images of patients' wounds to treating
      surgeons. To determine the feasibility of this technology, we compared bedside
      wound examination by onsite surgeons with viewing digital images of wounds by
      remote surgeons. METHODS: Over 6 weeks, 38 wounds in 24 inpatients were
      photographed with a Kodak DC50 digital camera (resolution 756 x 504 pixels/in2).
      Agreements regarding wound description (edema, erythema, cellulitis, necrosis,
      gangrene, ischemia, and granulation) and wound management (presence of healing
      problems, need for emergent evaluation, need for antibiotics, and need for
      hospitalization) were calculated among onsite surgeons and between onsite and
      remote surgeons. Sensitivity and specificity of remote wound diagnosis compared
      with bedside examination were calculated. Potential correlates of agreement,
      level of surgical training, certainty of diagnosis, and wound type were evaluated
      by multivariate analysis. RESULTS: Agreement between onsite and remote surgeons
      (66% to 95% for wound description and 64% to 95% for wound management) matched
      agreement among onsite surgeons (64% to 85% for wound description and 63% to 91%
      for wound management). Moreover, when onsite agreement was low (i.e., 64% for
      erythema) agreement between onsite and remote surgeons was similarly low (i.e.,
      66% for erythema). Sensitivity of remote diagnosis ranged from 78% (gangrene) to
      98% (presence of wound healing problem), whereas specificity ranged from 27%
      (erythema) to 100% (ischemia). Agreement was influenced by wound type (p < 0.01)
      but not by certainty of diagnosis (p > 0.01) or level of surgical training (p >
      0.01). CONCLUSIONS: Wound evaluation on the basis of viewing digital images is
      comparable with standard wound examination and renders similar diagnoses and
      treatment in the majority of cases. Digital imaging for remote wound management
      is feasible and holds significant promise for improving outpatient vascular wound
      care.

PMID- 9652472
TI  - Early operative intervention after thrombolytic therapy for primary subclavian
      vein thrombosis: an effective treatment approach.
AB  - PURPOSE: Effective treatment of primary subclavian vein thrombosis focuses on
      restoration of venous patency, relief of intrinsic stenosis, and decompression of
      the thoracic inlet. The appropriate method and timing for surgery, however, have
      not been not well defined. We conducted a study to determine an acceptable
      treatment approach. METHODS: A retrospective review evaluated 11 patients seen at
      our institution in an 8-year period. Seven patients were male and four were
      female, with an average age of 30 years (range 15 to 54 years). Two patients who
      had symptomatic stenosis without occlusion were omitted from the study. All
      patients with occlusion received urokinase therapy and underwent surgical
      decompression within 5 days of thrombolytic therapy. Five percutaneous
      transluminal angioplasties were attempted before operative intervention. Eleven
      decompressions were performed, including nine first-rib resections and two
      scalenectomies. Five operative venous procedures, consisting of thrombectomy with
      patch closure (n = 3) and bypass (n = 2), and seven venolysis procedures were
      performed. All patients received coumadin for 3 to 6 months after the operation.
      RESULTS: Urokinase therapy established wide venous patency in nine of the 11
      extremities treated, with the remaining two requiring thrombectomy for residual
      thrombus at the time of operation. One patient who underwent transluminal
      angioplasty before the operation had rethrombosis, and the remaining four showed
      no improvement in venous stenosis after the intervention. Eight of nine
      extremities treated by first-rib resection and one of two treated by scalenectomy
      were free of residual symptoms at follow-up. CONCLUSIONS: Preoperative use of
      percutaneous balloon angioplasty is ineffective and should be avoided in this
      setting. Surgical intervention within days of thrombolysis obviates the need for
      interim oral anticoagulation and enables patients to return to normal activity
      sooner.

PMID- 9652473
TI  - Patients with venous stasis ulceration have increased monocyte-platelet
      aggregation.
AB  - PURPOSE: Leukocyte activation has been implicated in the pathogenesis of venous
      stasis ulceration, but the involvement of activated platelets and leukocyte
      platelet aggregates has not been previously investigated. The purpose of this
      study was to determine whether patients with venous stasis ulceration have
      increased platelet activation and a propensity toward formation of leukocyte
      platelet aggregates. METHODS: Blood was drawn from the superficial veins of the
      leg just proximal to a venous stasis ulcer and from an antecubital vein in 14
      patients with venous stasis ulceration. Blood was also drawn from the antecubital
      vein of 14 volunteers without evidence of venous disease. Whole-blood flow
      cytometry was used to analyze the samples before and after activation with a
      panel of agonists for evidence of platelet activation and the formation of
      leukocyte-platelet aggregates. RESULTS: Patients with venous stasis ulceration
      had a greater number of monocyte-platelet aggregates in both the arm and leg
      samples than did the control subjects (p < 0.01). Furthermore, antecubital blood
      samples from patients with venous stasis ulceration stimulated with either
      thrombin-receptor agonist peptide, adenosine diphosphate, or phorbol myristate
      acetate formed more monocyte-platelet aggregates than did control samples (p <
      0.05). No differences in platelet activation or neutrophil-platelet aggregate
      formation were noted among the three sample groups. CONCLUSIONS: Patients with
      venous stasis ulceration have an increase in the number of monocyte-platelet
      aggregates in systemic venous blood as well as in venous blood adjacent to a
      venous stasis ulcer, implicating the monocyte as the leukocyte involved in the
      pathogenesis of venous stasis ulceration. No association was identified between
      the presence of a venous stasis ulcer and either neutrophil-platelet aggregation
      or the activation of individual platelets. Because platelet activation is
      necessary for the formation of monocyte-platelet aggregates, these data also
      suggest that monocyte-platelet aggregation is a more sensitive marker for in vivo
      platelet activation than is the identification of individual activated platelets.

PMID- 9652474
TI  - Evaluation of a novel hirudin-coated polyester graft to physiologic flow
      conditions: hirudin bioavailability and thrombin uptake.
AB  - PURPOSE: Our laboratory has developed methods required to covalently bind
      recombinant hirudin (rHir) to the surface of polyester vascular grafts. Using
      alkaline hydrolysis of the polyester surface, carboxyl-binding sites are created
      on the outer periphery of each fiber. A series of static, in vitro experiments
      have demonstrated that surface-bound rHir rapidly removes and inhibits activated
      human alpha-thrombin from the reaction system; however, the performance of this
      modified graft material under physiologic flow conditions was undefined. METHODS:
      An in vitro flow loop was used to evaluate structural stability of the 125I-rHir
      and 131I-albumin covalently bound to the surface of 6 mm interior diameter
      crimped polyester grafts exposed to either constant flow (n = 4; shear rate, 300
      sec(-1)) or pulsatile flow (n = 4; maximum shear rate, 780 sec(-1)) conditions
      for a 7-day period. In a separate series of experiments, the kinetics of thrombin
      rHir interaction were evaluated through perfusion of 125I-rHir-coated grafts (n =
      6) with 131I-thrombin for a 27-hour period under constant flow conditions.
      Identically prepared 125I-albumin-coated grafts (n = 3) were used as controls.
      RESULTS: Results of the stability experiments were independent of flow
      conditions, demonstrating moderate loss of both proteins, with rHir and albumin
      losses of 52.1% and 19.9% under constant flow and 49.1% and 21.6% under pulsatile
      flow, respectively. With results comparable with those of previous static
      experiments, rHir-coated grafts were significantly more effective at removing
      thrombin from the perfusion stream with 131I-thrombin binding densities of 3.08
      +/- 0.61 and 0.64 +/- 0.04 NIHU/cm2 (p < 0.01) for rHir-coated and albumin-coated
      grafts, respectively. Estimates of the total amount of thrombin inactivated
      during the perfusion period similarly demonstrated a marked difference between
      the rHir-coated and control graft segments (125 +/- 8 vs. 3 +/- 14 NIHU; p <
      0.005). CONCLUSIONS: These in vitro flow results illustrate that polyester grafts
      with covalently bound rHir can provide significant reductions in local thrombin
      concentration under physiologic flow conditions, and can serve as a foundation
      with which to understand the performance of these grafts when implanted in vivo
      under physiologic flow and shear rates.

PMID- 9652475
TI  - The differential effect of contrast agents on endothelial cell and smooth muscle
      cell growth in vitro.
AB  - PURPOSE: This study was designed to evaluate the effects of ionic and nonionic
      contrast agents on endothelial cell (EC) and smooth muscle cell (SMC)
      proliferation, and to determine the role of osmolality as the etiology of these
      effects. METHODS: Cultured bovine aorta EC and SMC were exposed to ionic
      (iothalamate meglumine) or nonionic (ioversol or iopamidol) contrast, or varying
      osmolar solutions of mannitol, for periods of 1, 3, 5, 10, or 20 minutes. Cells
      were then incubated in growth media at 37 degrees C and proliferation and
      structure were assessed 1, 3, 5, and 7 days later. RESULTS: Both EC and SMC
      showed decreased proliferation after brief exposure to both ionic and nonionic
      contrast. Proliferation was markedly decreased at 24 hours after exposure, and
      began to recover by day 3 after exposure. EC showed a significant decrease up to
      7 days after exposure to ionic contrast (p < 0.03), whereas SMC showed a
      significant decrease up to 7 days after exposure to nonionic contrast (p <
      0.001). The decrease in proliferation was directly dependent on the length of
      exposure to the contrast and the concentration of the contrast. EC proliferation
      decreased in proportion to increasing osmolality of the test solution (p < 0.05).
      SMC proliferation did not show a decrease proportional to osmolality. No change
      was observed in cell viability as assessed by LDH activity studies. After
      contrast exposure, bare areas with no cells present were noted in the previously
      confluent EC and SMC culture wells. Cell structure was altered immediately after
      exposure to contrast, with normal structure recovered by 24 hours after exposure.
      CONCLUSION: This study demonstrates that brief exposure to contrast agents
      injures EC and SMC, altering their structure and decreasing proliferation for up
      to 7 days in vitro. This response is both dose and time dependent. EC are more
      severely affected by ionic contrast, and SMC are more severely affected by
      nonionic contrast. EC injury appears to be mediated by the osmolar effect of the
      contrast, but the effects of contrast on SMC seem to be due to a different
      mechanism.

PMID- 9652476
TI  - Estrogen improves endothelial function.
AB  - PURPOSE: To determine the effect of estrogen on endothelium-dependent relaxation
      in the cutaneous microcirculation of women. METHODS: Three groups of women
      participated in the study. Group 1 (n = 20) was premenopausal and had a mean age
      of 39 years (range 24-50 years). Group 2 (n = 9) was postmenopausal and had a
      mean age of 58 years (range 53-65 years). Group 3 (n = 11) was postmenopausal and
      taking estrogen replacement therapy; the mean age was 53 years (range 43-58
      years). Eleven women in group 1 underwent testing twice, once during menstruation
      (mean serum estradiol level 73 +/- 30 pg/ml) and once during midcycle (mean serum
      estradiol level 268 +/- 193 pg/ml; p = 0.003). Single-point laser Doppler
      ultrasound and laser Doppler imaging with a scanner were used to measure
      vasodilatation in the forearm skin in response to iontophoresis of 1%
      acetylcholine (endothelium dependent) and 1% sodium nitroprusside (endothelium
      independent smooth muscle relaxant). RESULTS: All three groups were matched for
      body mass index and fasting glucose, total, high-density lipoprotein, and low
      density lipoprotein cholesterol and triglyceride levels. All women had normal
      blood pressure, and none smoked. Mean serum estradiol levels were 196 +/- 170
      pg/ml (group 1), 35 +/- 12 pg/ml (group 2), and 107 +/- 78 pg/ml (group 3) (p =
      0.004). Maximum microvascular vasodilatation (percentage increase over baseline)
      in response to acetylcholine was reduced in group 2 (93% +/- 43%) compared with
      group 1 (187% +/- 63%) and group 3 (142% +/- 56%) (p = 0.001). The response to
      sodium nitroprusside also was diminished in group 2 (73% +/- 27%) compared with
      group 1 (126% +/- 45%) and group 3 (100% +/- 32%) (p = 0.02). Within group 1 the
      acetylcholine response was higher during the midcycle phase (186% +/- 31%)
      compared with the menstrual phase (147% +/- 57%) (p < 0.05). The sodium
      nitroprusside response also was higher during the midcycle phase (144% +/- 31%)
      compared with the menstrual phase (94% +/- 41%) (p < 0.05) CONCLUSION: The
      results indicate that estrogens might enhance endothelium-dependent and
      endothelium-independent vasodilatation in the microcirculation of women.

PMID- 9652478
TI  - Regarding "Limb asymmetry in titanium Greenfield filters: clinically
      significant?".

PMID- 9652477
TI  - Treatment of a postoperative cervical chylous lymphocele by percutaneous
      sclerosing with povidone-iodine.
AB  - The development of postoperative leaks of the thoracic duct after neck dissection
      or vascular surgery of the subclavian and vertebral artery is a well-known but
      rare complication. Usually, an injury of the duct manifests immediately after the
      operation with chylous drainage. Presentation as a postoperative lymphocele is
      rare. Operative treatment may be an option, but identification of the leak often
      is impossible, resulting in a high rate of failure. Percutaneous catheter
      drainage in combination with sclerosis with povidone-iodine has proved to be
      highly effective in obliterating pelvic lymphoceles but has not been reported in
      patients who have undergone vascular surgery in the neck. We present a case in
      which a povidone-iodine solution was used successfully in percutaneous sclerosis
      of a cervical lymphocele after transposition of the left subclavian artery to the
      left common carotid artery.

PMID- 9652479
TI  - Neck influences on the spatial properties of vestibulospinal reflexes in
      decerebrate cats: role of the cerebellar anterior vermis.
AB  - The vestibulospinal (VS) reflexes elicited by animal rotation modify the activity
      of limb musculature, thus preserving balance and postural stability. We
      investigated whether the orientation of these postural responses is strictly
      dependent upon the direction of head displacement or else can be modified by
      extralabyrinthine inputs to the goal of stabilizing body position. The
      experiments were performed in decerebrate cats, in which the effects of static
      body-to-head displacements were tested on the multiunit EMG responses of the
      medial head of the triceps brachii to wobble of the whole animal at 0.15 Hz, 10
      degrees, both in the clockwise (CW) and counterclockwise (CCW) direction. These
      stimuli allowed us to determine the muscle response vector, whose orientation
      component corresponds to the direction of head displacement giving rise to the
      maximal EMG response. When the animal body was kept straight with respect to the
      head, the triceps response vector was always oriented close to the transverse
      axis, pointing to the side-down direction. Following 30 degrees of body-to-head
      displacement around a vertical axis passing through the first-second cervical
      joints, the response vectors of both the left and the right muscles shifted in
      the same direction of body rotation, thus remaining approximately perpendicular
      to the body axis. The change in muscle vector orientation corresponded on the
      average to the angle of body-to-head displacement. Only slight changes in
      amplitude of the muscle responses were observed. These findings imply that the
      maximal activation of the triceps brachii always occurred for the same direction
      of body displacement, irrespective of the pattern of discharge of vestibular
      afferents, which is determined by the direction of head displacement. The
      rotation of the triceps response vector induced by body-to-head displacement was
      reduced or suppressed by inactivation of the ipsilateral cerebellar anterior
      vermis, following local microinjection of the GABA(A) agonist muscimol. These
      findings indicate that 1) the sensory input which results from changing the body
      position with respect to the head, probably originating from neck receptors, is
      able to modify the pattern of the VS reflexes, which appear to be organized in a
      body-centered reference frame, and 2) the cerebellar vermis is required for the
      proper execution of this sensorimotor transformation.

PMID- 9652480
TI  - Post-rotatory nystagmus and turning sensations after active and passive turning.
AB  - We measured post-rotatory nystagmus and sensations of body rotation in standing
      subjects brought to rest in the dark after 3 minutes of each of the following
      conditions: 1) passive turning about the mid-body axis, involving only vestibular
      stimulation, 2) active turning about the mid-body axis, involving both vestibular
      stimulation and motor-proprioceptive activity in the legs, and 3) stepping round
      while remaining facing in the same direction on the center of a rotating platform
      with the head held in a stationary holder (apparent turning), involving only
      motor-proprioceptive activity. The same acceleration-velocity profile was used in
      all conditions. Post-rotatory nystagmus (slow phase) occurred in the same
      direction to passive body turning and was reduced in velocity after active body
      turning. After apparent turning, nystagmus was in the opposite direction as
      attempted body turning. Our theoretical analysis suggests that nystagmus after
      active turning should conform to the mean of the responses after passive and
      apparent turning rather than to their sum. The results conform more closely to
      the mean than to the sum, but with greater weight given to vestibular inputs than
      to motor-proprioceptive inputs. Post-rotatory sensations of self-rotation were in
      the expected opposite direction after passive turning and were lower in magnitude
      after active turning. After apparent turning, sensations of self-rotation were in
      the same direction as those after attempted turning--an effect known as the
      antisomatogyral illusion.

PMID- 9652481
TI  - Spectral analysis of low-frequency, active-head vestibulo-ocular reflex
      responses.
AB  - Useful medical diagnostic information has been reported from low-frequency
      rotational testing of the horizontal vestibulo-ocular reflex (VOR) of patients
      with vestibular disorders. Servocontrolled rotating systems have been used as the
      only practical method to generate stimuli over lower VOR frequency response
      ranges, the decade from 0.01 to 0.1 Hz. Active head movements have been used for
      testing the human VOR at higher frequencies, exceeding 0.5 Hz. We examined
      whether active head movements could be used also to test the VORs of subjects
      over lower frequency ranges, extending to 0.02 Hz. We used a swept-frequency,
      active head movement protocol to generate a broad-band stimulus. Eye position was
      recorded with electro-oculography. Head velocity was recorded with a rotational
      sensor attached to a head band. Six individual test epochs from human subjects
      were concatenated to form complex, periodic waveforms of head and eye velocity,
      75 seconds in duration. Broad-band cross-spectral signal processing methods were
      used to compute horizontal VOR system characteristics from these waveforms
      extending from 0.02 to 2 Hz. The low-frequency VOR data appeared to originate
      from amplitude modulation of high-frequency active movements, acting as carrier
      signals. Control experiments and processing of simulated data from a known system
      excluded the possibility of signal processing artifacts. Results from six healthy
      subjects showed low-frequency gains and phase values in ranges similar to those
      from published rotational chair studies of normal subjects. We conclude that it
      is feasible to test the human VOR over extended low-frequency ranges using active
      head movements because of amplitude modulation of the head and eye signals.

PMID- 9652482
TI  - Why do benign paroxysmal positional vertigo episodes recover spontaneously?
AB  - It is well known that most episodes of benign paroxysmal positional vertigo
      (BPPV), even in untreated, recover spontaneously in 2 to 6 weeks. In the present
      study, we put forward the hypothesis that this is mainly due to the fact that
      endolymph, owing to its low calcium content (20 microM) is able to dissolve
      otoconia. To support this, the fate of frog saccular otoconia immersed in normal
      endolymph (Ca2+ content 20 microM) and in Ca2+-rich endolymphatic fluids (up to
      500 microM) was studied by observing the crystals at regular intervals for 3
      weeks. The results demonstrated that normal endolymph can dissolve otoconia very
      rapidly (in about 20 hours). When the endolymphatic Ca2+ content was increased
      (50 to 200 microM) otoconia dissolution time was slowed down (about 100 to 130
      hours, respectively) and completely stopped when the endolymphatic Ca2+ content
      was of 500 microM. The present results therefore suggest that the major process
      involved in the spontaneous recovery of BPPV episodes is the capability of the
      endolymph to dissolve dislodged otoconia.

PMID- 9652483
TI  - Adaptation of the VOR in patients with low VOR gains.
AB  - Six subjects with histories of vertigo and with vestibulo-ocular reflex (VOR)
      gains less than 0.5 were tested in an adaptation protocol. After initial VOR
      testing in the dark, the subjects had a computer-driven visual display system
      placed on their heads. The system had the capability for variation of visual
      image magnification. The magnification was set to be 5% greater than the
      subject's average VOR gain. Subjects then performed active head movements as they
      carried out a visual searching task looking for objects in a panoramic scene.
      After 6 minutes with each image, the magnification was increased by 3 to 5%. The
      process was repeated for a total of 5 images, for a total increase in
      magnification of approximately 20% over 30 minutes. The VOR gain was measured
      again. In 17 of 18 conditions tested, the VOR gain increased. The average
      increase was 16%. Significant increases in VOR gain occurred at 0.32 and 0.64 Hz.
      The VOR gain increase in these patients occurred in a visual environment that
      lowered VOR gain in normal subjects. These results suggest that the VOR has an
      adaptation mechanism tuned to correct for small changes in required gain. Further
      research is necessary to determine if this method can result in persistent VOR
      gain improvements and reduction in symptoms and disability in patients with
      vestibular disorders.

PMID- 9652484
TI  - Examination of two methods for statistical analysis of data with magnitude and
      direction emphasizing vestibular research applications.
AB  - When the dependent (or response) variable response variable in an experiment has
      direction and magnitude, one approach that has been used for statistical analysis
      involves splitting magnitude and direction and applying univariate statistical
      techniques to the components. However, such treatment of quantities with
      direction and magnitude is not justifiable mathematically and can lead to
      incorrect conclusions about relationships among variables and, as a result, to
      flawed interpretations. This note discusses a problem with that practice and
      recommends mathematically correct procedures to be used with dependent variables
      that have direction and magnitude for 1) computation of mean values, 2)
      statistical contrasts of and confidence intervals for means, and 3) correlation
      methods.

PMID- 9652485
TI  - Magnetoencephalography and magnetic source imaging.
AB  - Current brain imaging techniques, such as computed tomography (CT) and magnetic
      resonance imaging (MRI), provide noninvasive, high-resolution images that depict
      fine anatomic structure and delineate pathology by control of image contrast and
      sensitivity to the physicochemical microenvironment. These methods, although
      invaluable for the identification, characterization, and localization of lesions,
      do not provide any assessment of the functional viability of brain tissues, nor
      of the spatial organization of sensory, motor, and cognitive systems. However,
      such additional functional information is of great significance to the clinician
      in the determination of treatment strategies and patient management.

PMID- 9652486
TI  - Hand preference and magnetic resonance imaging asymmetries of the central sulcus.
AB  - Hand preference is perhaps the most evident behavioral asymmetry observed in
      humans. Anatomic brain asymmetries that may be associated with hand preference
      have not been extensively studied, and no clear relationship between asymmetries
      of the motor system and hand preference have been established. Therefore, using
      volumetric magnetic resonance imaging methodologies, the surface area of the hand
      representation was measured along the length of the central sulcus in 15
      consistent right- and 15 left-handers matched for age and gender. There was a
      significant leftward asymmetry of the motor hand area of the precentral gyrus in
      the right-handers, but no directional asymmetry was found in the left-handers.
      When asymmetry quotients were computed to determine the distribution of
      interhemispheric asymmetries, the left motor bank was greater than the right
      motor bank in 9 of 15 right-handers, the right motor bank was greater than the
      left motor bank in 3 of 15 right-handers, and the motor banks were equal in 3 of
      15 right-handers. In contrast, among left-handers, the left motor bank was
      greater than the right motor bank in 5 of 15, the right motor bank was greater
      than the left motor bank in 5 of 15, and the motor banks were equal in 5 of 15.
      Although no direct measure of motor dexterity and skill was performed, these data
      suggest that anatomic asymmetries of the motor hand area may be related to hand
      preference because of the differences in right-handers and left-handers.
      Furthermore, the predominant leftward asymmetry in right-handers and the random
      distribution of asymmetries in the left-handers support Annett's right-shift
      theory. It is unclear, however, whether these asymmetries are the result of
      preferential hand use or are a reflection of a biologic preference to use one
      limb over the other.

PMID- 9652487
TI  - The effects of rotation on spatial attention.
AB  - Unilateral spatial neglect can be reduced by cold water caloric stimulation of
      the contralesional ear. Three hypotheses may account for this response. Caloric
      stimulation may increase the arousal of the damaged hypoaroused hemisphere.
      Moving stimuli to ipsilesional space improves the performance of patients with
      neglect. Caloric stimulation may move viewer-centered spatial maps in an
      ipsilesional direction. Unilateral neglect may be related to a spatial
      attentional bias. Vestibular stimulation may temporarily influence this bias. To
      learn if vestibular stimulation may induce an attentional spatial bias, the
      authors studied eight normal subjects by having these subjects attempt to bisect
      lines before and during vestibular stimulation. If caloric stimulation alters
      neglect because it changes the attentional spatial bias, the authors should be
      able to induce neglect in normal subjects by pertubating the vestibular system.
      Vestibular stimulation was induced by spinning a chair and then abruptly stopping
      the spinning chair. The authors found that after normal subjects were rotated to
      the left, they misbisected lines to the left but did not misbisect lines after
      they were rotated to the right. Although these results support the postulate that
      vestibular stimulation can induce an attentional spatial bias, the authors'
      results also suggest that there are intrinsic attentional asymmetries.

PMID- 9652488
TI  - The evolution of alexia and simultanagnosia in posterior cortical atrophy.
AB  - Early alexia and higher visual impairments characterize Posterior cortical
      atrophy (PCA), a progressive dementing syndrome most often caused by Alzheimer
      disease. Posterior cortical atrophy is rare, and the nature of the visual
      impairments in PCA are unclear. The authors observed two patients who had an
      insidiously progressive reading difficulty characterized by letter-by-letter
      reading and otherwise intact cognitive functions. Over time, these patients
      developed "ventral simultanagnosia" with preserved detection of multiple stimuli
      but inability to interpret whole scenes. Subsequently, they progressed to Balint
      syndrome with "dorsal simultanagnosia," optic ataxia, and oculomotor apraxia.
      Structural imaging was normal, but functional imaging revealed posterior cortical
      dysfunction. On a letter reading task, both patients had a word superiority
      effect, and on a whole word reading task, they could not read most words with
      missing or crosshatched letters. An inability to assess whole scenes progressed
      to an inability to detect more than one stimulus in an array. These findings
      suggest an evolution of PCA with progressive difficulty in visual integration
      beginning with letters, progressing to whole scenes, and culminating in Balint
      syndrome. These changes may reflect an extension of the pathophysiology of PCA
      from the extrastriate visual cortex to its occipitotemporal and occipitoparietal
      connections.

PMID- 9652489
TI  - Functional imaging: heterogeneity in task strategy and functional anatomy and the
      case for individual analysis.
AB  - To learn more about the functional anatomy of language, the authors used
      [99mTc]HMPAO single photon emission computed tomography (SPECT) functional
      imaging to study nonword rhyming, lexical-semantics and syntax. The authors did
      not find any task-related differences in cerebral blood flow using region-by
      region analysis of variance. This led them to examine individual subject's task
      related patterns of cerebral blood flow. This analysis revealed regions of
      interest with little or no change but also regions with changes as great as 30%.
      There was marked subject-to-subject variability in the pattern of blood flow,
      which precluded statistically significant results using analysis of variance. An
      alternative analytic strategy based on numbers of subjects exceeding a minimum
      threshold task-related change in cerebral blood flow was tested and shows promise
      in identifying commonalities and differences in individual task-related blood
      flow patterns. The authors conclude that the complex and difficult to interpret
      pattern of blood flow changes observed in this study reflect in considerable part
      the combined effects of variability in task strategy, owing in part to
      insufficiently constrained task performance, and variability in functional
      anatomy. The authors also tested the differences in results achieved with simple
      normalization and analysis of covariance approaches and found them to be
      insignificant.

PMID- 9652490
TI  - Patterns and associates of hyperphagia in patients with dementia.
AB  - This study examined patterns and associates of excessive eating (hyperphagia) in
      a community-based registry of patients with dementia. From patients enrolled in
      the Mayo Clinic Alzheimer's Disease Patient Registry (n = 439), 39 were
      identified with excessive eating reported on the Behavior Symptom Checklist at
      some time during their illness. They were matched for age, gender, duration of
      disease, and Global Deterioration Scale (GDS) score to "normal eaters."
      Annualized weight change was determined based on weight from the 6 months before
      the evaluation to weight 6 months after the evaluation. Annualized weight change
      scores were not significantly different between excessive eaters and normal
      eaters nor between wanderers and nonwanderers. In cross-sectional analysis,
      univariate modeling suggested age at onset, GDS, and Mini-Mental State
      Examination score to be significant predictors of excessive eating. Using
      multivariate logistic model with backward elimination, only age of onset and GDS
      were retained as associates of excess eating. Rater type also emerged as a
      significant predictor for excessive eating with family raters reporting this
      behavior in 16% of patients compared to 5% for other raters. In chi-square
      analyses excessive eating was associated with greater frequency of wandering,
      unpredictable behavior, inappropriate dressing, inappropriate bodily concerns,
      and threatening self-harm. Associates of excess eating were subsequently examined
      separately in wandering and nonwandering excessive eaters. Logistic modeling
      suggested that among nonwanderers, patients who were younger but more severely
      demented were likely to have reported excessive eating. These results suggest
      hyperphagia to be present in approximately 10% of a community-based cohort of
      patients with dementia and associated with increasing functional decline.
      Excessive eating does not appear to arise from memory dysfunction, but for
      wanderers may result from needing increased caloric intake because of increased
      activity levels. Thus, for wandering excessive eaters, it may be appropriate to
      endure the eating to ensure appropriate caloric intake. Nonwandering excessive
      eaters were younger, had greater dementia severity, and had more unpredictable
      behavior. They may have dementia with prominent frontal lobe involvement and may
      respond to any food stimulus respective of hunger. Restricting food exposure may
      be an effective management intervention for them.

PMID- 9652491
TI  - Olfactory reference syndrome in a patient with partial epilepsy.
AB  - A 49-year-old man with right temporal lobe epilepsy developed the chronic
      delusion that his body emitted a foul odor (olfactory reference syndrome). Before
      the delusional symptoms, he had partial seizures with unpleasant olfactory
      hallucinations. Subsequently ictal olfactory symptoms abated but a disabling
      delusional syndrome developed. The only prior case of the olfactory reference
      syndrome in a patient with epilepsy had a right frontal lesion. The case further
      supports the association of right hemisphere lesions and delusional disorders.

PMID- 9652492
TI  - Remote memory after basal forebrain damage.

PMID- 9652493
TI  - Introduction. Monothematic courses.

PMID- 9652494
TI  - Clinical manifestations of seronegative spondylarthropathies.
AB  - Seronegative spondylarthropathies include ankylosing spondylitis, Reiter's
      syndrome and reactive arthritis, psoriatic arthritis, arthritis associated with
      ulcerative colitis and Crohn's disease, plus other forms which do not meet the
      criteria for definite categories and are called undifferentiated. Recently two
      sets of classification criteria have been proposed for the entire group including
      undifferentiated forms: the European Spondylarthropathy Study Group and the Amor
      criteria. The prevalence of spondylarthropathies is directly correlated with the
      prevalence of the HLA-B27 antigen in the population. The highest prevalence of
      ankylosing spondylitis (4.5%) has been found in Canadian Haida Indians, where 50%
      of the population is B27 positive. Among Europeans the frequency of the B27
      antigen in the general population ranges from 3 to 13% and the prevalence of
      ankylosing spondylitis is estimated to be 0.1-0.23%. Seronegative
      spondylarthropathies have common clinical and radiologic manifestations:
      inflammatory spinal pain, sacroiliitis, chest wall pain, peripheral arthritis,
      peripheral enthesitis, dactylitis, lesions of the lung apices, conjunctivitis,
      uveitis and aortic incompetence together with conduction disturbances. All of
      these may also occur in isolation.

PMID- 9652495
TI  - Diffuse idiopathic skeletal hyperostosis.
AB  - OBJECTIVE: To describe the axial and appendicular skeleton findings of diffuse
      idiopathic skeletal hyperostosis. To analyze the role of conventional
      radiography, computed tomography (CT) and magnetic resonance imaging (MRI) in the
      diagnosis of this condition. To discuss the differential diagnosis and diagnostic
      pitfalls of this disease. MATERIAL AND METHODS: The involvement of vertebral and
      extravertebral sites including the pelvis, calcaneum, ulnar olecranon, and
      patella is frequently found in the literature. The lesions described are the
      anterior and lateral ossification of the spine, hyperostosis at sites of tendon
      and ligament insertion, ligamentous ossification, and periarticular osteophytes.
      The criteria for the diagnosis of diffuse idiopathic skeletal hyperostosis
      involving the spine are: flowing ossification along the anterior and
      anterolateral aspects of at least four contiguous vertebrae, preserved
      intervertebral disc height, no bony ankylosis of the posterior spinal facet
      joints, and finally no erosion, sclerosis or bony ankylosis of the sacroiliac
      joints. RESULTS: The disease has about the same frequency in men (65%) and women
      (35%); it is most common in the thoracic spine and occurs less frequently in the
      lumbar and cervical spine. The disease most commonly presents in the sixth and
      seventh decades of life and its estimated frequency in the elderly is 5-15%.
      Signs and symptoms include stiffness and pain in the back, dysphagia due to
      direct esophageal compression/distorsion, pain related to associated tendinitis,
      myelopathy related to core compression associated to the ossification of the
      posterior longitudinal ligament, and pain related to vertebral complications-
      e.g. fracture/subluxation. CONCLUSION: While conventional radiography clearly
      confirms the diagnosis of diffuse idiopathic skeletal hyperostosis, CT and MRI
      better detect associated findings (e.g. ossification of the posterior
      longitudinal ligament) and complications (e.g. spinal cord compressive
      myelomalacia).

PMID- 9652496
TI  - Seronegative spondylarthropathies: imaging of spondylitis, enthesitis and
      dactylitis.
AB  - Sacroiliitis is an indispensable condition for the diagnosis of ankylosing
      spondylitis according to the present criteria and is usually diagnosed on
      standard anteroposterior radiographs of the pelvis. In cases with suspicious
      abnormalities (grade 1 of the New York criteria) CT permits the diagnosis since
      it shows a higher degree of sacroiliitis. MRI is superior to CT in the early
      diagnosis as it can detect the cartilage abnormalities which precede bony
      changes. 'Romanus lesions' with 'shiny corners', 'squaring' of the vertebral
      bodies, syndesmophytes, spondylodiscitis and osteoporosis are the radiological
      findings of ankylosing spondylitis. The nonmarginal, asymmetric, coarse and broad
      syndesmophytes of psoriatic spondylitis and spondylitis associated with Reiter's
      syndrome resemble the flowing bone outgrowths of diffuse idiopathic skeletal
      hyperostosis (DISH). The ossification of the posterior longitudinal ligament and
      of the flavum ligament are rare manifestations of ankylosing spondylitis.
      Peripheral extra-articular enthesitis is a clinical hallmark of seronegative
      spondylarthropathies. Plain film radiography shows erosions and spurs but only in
      advanced phases. US shows the swelling of the entheses and the peritendinous soft
      tissues and the distension of adjacent bursae by fluid collection. MRI shows the
      inflammation of the bone adjacent to the insertion as well as the soft tissue
      changes. Dactylitis is another typical manifestation of seronegative
      spondylarthropathies. In the past it was thought to be due to concomitant
      tenosynovitis and arthritis. Recently, however, we have demonstrated with US and
      MRI that the 'sausage-like' appearance is due to the flexor tenosynovitis and
      that joint capsule distension is not indispensable.

PMID- 9652497
TI  - The clinical features of rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by
      progressive damage of synovial-lined joints and variable extra-articular
      manifestations. Tendon and bursal involvement are frequent and often clinically
      dominant in early disease. RA can affect any joint, but it is usually found in
      metacarpophalangeal, proximal interphalangeal and metatarsophalangeal joints, as
      well as in the wrists and knee. Articular and periarticular manifestations
      include joint swelling and tenderness to palpation, with morning stiffness and
      severe motion impairment in the involved joints. The clinical presentation of RA
      varies, but an insidious onset of pain with symmetric swelling of small joints is
      the most frequent finding. RA onset is acute or subacute in about 25% of
      patients, but its patterns of presentation also include palindromic onset,
      monoarticular presentation (both slow and acute forms), extra-articular synovitis
      (tenosynovitis, bursitis), polymyalgic-like onset, and general symptoms (malaise,
      fatigue, weight loss, fever). The palindromic onset is characterized by recurrent
      episodes of oligoarthritis with no residual radiologic damage, while the
      polymyalgic-like onset may be clinically indistinguishable from polymyalgia
      rheumatica in elderly subjects. RA is characteristically a symmetric erosive
      disease. Although any joint, including the cricoarytenoid joint, can be affected,
      the distal interphalangeal, the sacroiliac, and the lumbar spine joints are
      rarely involved. The clinical features of synovitis are particularly apparent in
      the morning. Morning stiffness in and around the joints, lasting at least 1 h
      before maximal improvement is a typical sign of RA. It is a subjective sign and
      the patient needs to be carefully informed as to the difference between pain and
      stiffness. Morning stiffness duration is related to disease activity. Hand
      involvement is the typical early manifestation of rheumatoid arthritis. Synovitis
      involving the metacarpophalangeal, proximal interphalangeal and wrist joints
      causes a characteristic tender swelling on palpation with early severe motion
      impairment and no radiologic evidence of bone damage. Fatigue, feveret, weight
      loss, and malaise are frequent clinical signs which can be associated with
      variable manifestations of extra-articular involvement such as rheumatoid
      nodules, vasculitis, hematologic abnormalities, Felty's syndrome, and visceral
      involvement. Although there is no laboratory test to exclude or prove the
      diagnosis of rheumatoid arthritis, several laboratory abnormalities can be
      detected. Abnormal values of the tests for evaluation of systemic inflammation
      are the most typical humoral features of RA. These include: erythrocyte
      sedimentation rate, acute phase proteins and plasma viscosity. Erythrocyte
      sedimentation rate and C-reactive protein provide the best information about the
      acute phase response. The C-reactive protein is strictly correlated with clinical
      assessment and radiographic changes. Plain film radiography is the standard
      investigation to assess the extent of anatomic changes in rheumatoid arthritis
      patients. The radiographic features of the hand joints in early disease are
      characterized by soft tissue swelling and mild juxtaarticular osteoporosis. In
      the the past 10 years, ultrasonography has gained acceptance for studying joint,
      tendon and bursal involvement in RA. It may improve the early clinical assessment
      and the follow-up of these patients, showing such details as synovial thickening
      even within finger joints. Other imaging techniques, such as magnetic resonance,
      computed tomography and scintigraphy may provide useful information about both
      the features and the extent for anatomic damage in selected rheumatoid arthritis
      patients. The natural history of the disease is poorly defined; its clinical
      course is fluctuating and the prognosis unpredictable. RA is an epidemiologically
      relevant cause of disability. An adequate early treatment of RA may alter the
      diseas

PMID- 9652498
TI  - Rheumatoid arthritis: follow-up and response to treatment.
AB  - OBJECTIVE: To assess the role of diagnostic imaging techniques in the
      identification and follow-up of the anatomical damage induced by the chronic
      inflammatory process of rheumatoid arthritis (RA) not only to study the natural
      history of the disease but also and especially to assess the long-term response
      to disease-modifying anti-rheumatic drugs (DMARD). MATERIALS AND METHODS: The
      relative literature data were reviewed and compared with our personal experience
      with different imaging modalities such as conventional radiography (CR),
      ultrasound (US) and magnetic resonance imaging (MRI). RESULTS: Several radiologic
      techniques have been used over the years to study articular damage in RA: they
      describe and quantify the articular damage (semi-quantitative analysis) based on
      a series of parameters and elementary anatomical lesions which are given a rising
      score. For its sensitivity in detecting early disease signs and the possibility
      to express anatomical damage progression quantitatively, Sharp's index is
      considered the best tool for evaluating RA patients. The close correlation
      between clinical parameters and the radiologic scores obtained regardless of the
      method applied led to a new concept of anatomical damage related to the
      'radiologic progression of the disease' which is a more precise measure of RA
      severity than the single isolated radiograph. The progression of radiologic
      damage in rheumatoid arthritis is expressed as the number or proportion of new
      eroded joints/year: independent of the index adopted and the terms used to
      express progression, severe radiologic damage occurs in the early disease stage,
      involving approximately 2% of the joints within about 1 year, and 13% within 2
      years, with an estimated average annual progression of 1.3%. Radiologic
      techniques evaluate the anatomical damage in the course of RA only with reference
      to the osseous component of the joint and therefore apply to a disease stage that
      is largely irreversible. MRI and US detect the soft-tissue damage occurring in
      the earlier phases and are more likely to respond to early treatment. The former
      technique appears to be useful to detect soft-tissue damage like synovial pannus,
      intra- and periarticular and peritendinous effusion, capsuloligamentous articular
      and tendon changes. Its high sensitivity for minimal bone erosions and
      chondromalacia has been demonstrated. US allows to demonstrate a wide range of
      soft-tissue changes of the hand and wrist. Joint-cavity widening, loss of
      cartilage definition, bone erosions, widening of flexor tendon sheath and tendon
      structure are also well depicted on ultrasound images. CONCLUSIONS: CR is the
      central tool in the diagnosis, staging and follow-up of RA patients and in
      general in the assessment of treatment efficacy; MRI and US are complementary
      tools.

PMID- 9652499
TI  - Rheumatoid arthritis: sequences.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is an autoimmune disorder of unknown
      etiology characterized by symmetric, erosive synovitis and sometimes multisystem
      involvement. It affects 1% of the adult population and exhibits a chronic
      fluctuating course which may result in progressive joint destruction, deformity,
      disability and premature death. We review the literature data relative to the
      peculiar pathologic features of the disease shown by diagnostic imaging
      techniques. METHODS: All our patients were classified according to the diagnostic
      criteria of the American Rheumatism Association (1987). Plain radiography remains
      the diagnostic technique of choice, but ultrasound (US), computed tomography (CT)
      and magnetic resonance imaging (MRI) are also used. RESULTS: Clinically articular
      involvement presents as pain, swelling, stiffness and motion impairment. The
      patients with positive rheumatoid factor are > 70% likely to develop joint damage
      or erosions within 2 years of disease onset. Any joint can be involved, but the
      proximal interphalangeal and metacarpophalangeal joints of the hand and the wrist
      are preferential sites, as well as the metatarsophalangeal joint of the foot, the
      knee and the joints of the shoulder, the ankle and the hip. Symmetry is the
      hallmark of joint involvement. The synovium of bursae and tendon sheaths is also
      affected. Soft tissue (subcutaneous nodules), muscles (weakness and atrophy) and
      vessels (vasculitis) may also be involved. Systemic involvement may result in
      Felty's syndrome, metabolic bone disorders (i.e. osteoporosis), Sjogren syndrome
      and pleuropulmonary abnormalities (pleural effusion, fibrosing alveolitis,
      constrictive bronchiolitis). The earliest abnormalities consist in synovial
      proliferation, soft tissue swelling, and osteoporosis. At a slightly later stage,
      the inflamed synovial tissue ('pannus') extends across the cartilage surface,
      leading to chondral erosions and small bone erosions at the joint margin (bare
      areas). Marginal and central erosions follow in advanced stages and finally
      fibrous ankylosis, joint deformities (subluxations and dislocations), fractures
      and fragmentations are typical findings of more advanced RA. CONCLUSION: RA is a
      frequent joint disorder with a characteristic radiographic picture. Joint
      involvement patterns are sufficiently common to permit accurate diagnosis,
      especially when fusiform soft tissue swelling, regional osteoporosis, marginal
      and central erosions and diffuse loss of interosseous space are present.
      Conventional radiography remains the standard imaging technique for joint studies
      in the patients with suspected RA. US is recommended to diagnose soft tissue
      involvement (joint effusion). CT is very useful for showing abnormal processes in
      complex joints (sacroiliac and temporomandibular joints and craniocervical
      junction) which are difficult to depict completely with conventional radiography.
      Magnetic resonance applications include the assessment of disease activity: in
      particular, this technique may be the only tool differentiating synovial fluid
      and inflammatory pannus.

PMID- 9652500
TI  - Joint impingement syndrome: clinical features.
AB  - Joint impingement is a painful syndrome caused by the friction of joint tissues,
      which is both the cause and the effect of altered joint biomechanics. From the
      anatomical and clinical viewpoints, these syndromes are classified as bone
      impingement, soft tissue impingement and entrapment neuropathy, depending on what
      joint portion impinges on the others. We considered the most important
      impingement syndromes of the upper and the lower limbs from the clinical
      viewpoint. As for the upper limb, supraspinatus impingement is a frequent cause
      of shoulder pain in both athletes and the normal population; the painful
      subacromial arch is a typical sign of the rotator cuff impingement syndrome and
      of outlet and non-outlet impingement as well. As for the elbow, we considered
      both medial and lateral impingement. The carpal tunnel syndrome is the most
      common peripheral entrapment neuropathy of the upper limb; it is caused by
      compression of the median nerve at the wrist. We considered the main causes of
      carpal tunnel narrowing and the relative clinical findings. As for the lower
      limb, we considered the iliotibial band friction syndrome, which is the most
      common overuse syndrome of the knee and the ankle impingement syndrome. The
      latter includes anterolateral impingement (with chronic anterolateral and lateral
      pain and ankle instability), sinus tarsi impingement, anterior impingement (with
      pain during foot dorsiflection and posterior impingement. The tarsal tunnel
      syndrome is the most important ankle entrapment neuropathy causing burn pain and
      paresthesias in the toes and sole of the foot.

PMID- 9652501
TI  - Shoulder impingement syndromes.
AB  - OBJECTIVE: Not all shoulder pain conditions are a consequence of rotator cuff
      injuries secondary to anterior subacromial impingement. Additional causative
      forms have been identified and classified as posterosuperior glenoid rim,
      subcoracoid and suprascapular nerve (at spinoglenoid notch) impingement
      syndromes. MATERIAL AND METHODS: We reviewed 206 consecutive magnetic resonance
      examinations carried out with conventional T1- and T2-weighted spin-echo and
      gradient-echo sequences in patients complaining of shoulder pain. Adjunctive
      sequences were acquired with the involved arm positioned in abduction and
      external rotation. RESULTS: Anterior subacromial impingement is only one of the
      possible causes of shoulder disorders. Posterosuperior glenoid rim impingement is
      the most frequent cause of shoulder pain in young throwers. Subcoracoid and
      spinoglenoid notch suprascapular nerve impingement are additional forms that must
      be considered in the differential diagnosis because of their frequent occurrence
      in routine clinical practice. CONCLUSION: Magnetic resonance imaging is the most
      useful diagnostic modality for shoulder disorders.

PMID- 9652502
TI  - Sports injuries in the pelvis and hip: diagnostic imaging.
AB  - We discuss the role of imaging techniques in examining the athletes with sports
      injuries involving the pelvis and the hip. Pelvis and hip pain is of difficult
      clinical clarification because of the various athletic injuries which may affect
      the bone or soft tissues at different anatomic sites. Moreover, the symptoms of
      pelvis and hip injuries are similar in most cases and they are often diffuse and
      atypical. Diagnostic imaging can play an essential role because treatment success
      depends on a correct diagnosis and these techniques can actually differentiate
      the most frequent causes of pelvis and hip sports injuries such as groin strain,
      osteitis pubis, ischial intersection syndrome, snapping hip, stress fractures,
      hernias and avulsion fractures. Finally, we discuss the role of magnetic
      resonance imaging in detecting the causes of hip pain other than sports injuries,
      such as avascular necrosis, reflex sympathetic dystrophy syndrome, herniation
      pit, acetabular labrum injuries. To conclude, diagnostic imaging techniques
      currently permit the direct and noninvasive depiction of pelvis and hip
      conditions. Particularly, magnetic resonance imaging is very helpful in detecting
      injury site, extent and characteristics; it can also predict the time period an
      athlete will be disabled and help define the best treatment planning.

PMID- 9652503
TI  - Knee impingement syndromes.
AB  - INTRODUCTION: The so-called knee impingement syndromes are very frequently
      reported in both professional and amateur sportsmen. PURPOSE: The objective of
      our study was to classify the most frequent knee changes responsible for such
      syndromes considering both pathology and diagnostic work-up. MATERIAL AND
      METHODS: Our patients complained of aspecific symptoms related to articular
      meniscal, ligament or cartilage, conditions. The site of pain was periarticular
      and there was no apparent sign of acute traumatic events. All individuals, aged
      16-55, practised sports at different levels and women were the majority of the
      sample. The study was carried out from 1995 to 1997 and all the medical records
      presented in occasion of the sports-medicine check-up were reviewed. RESULTS: The
      sites of symptom onset were divided into medial, lateral, anterior and posterior.
      For each of them the most frequent conditions which could be defined as
      impingement syndromes, were defined paying particular attention to the possible
      methods of diagnosis useful to classify the disorder. As for anterior syndromes,
      patellofemoral disorders were the most frequent findings. They were associated
      with either incorrect torsion movements of the lower limbs or local dysplasia.
      Alterations in the single skeletal and cartilage structures were reported. Always
      referring to anterior syndromes, Hoffa's fat pad imflammation and the jumper's
      knee were a less frequent finding. As for posterior impingement syndromes, the
      most frequent abnormalities involved the insertional tract of the midcalf muscle
      associated with bursa reaction and insertional popliteus hypertrophy. As for
      medial syndromes, the most frequent abnormality involved the parapatellar
      synovial fold whose symptoms can be often mistaken for a meniscal injury. Less
      frequent is the involvement of the 'pes anserinus' tendinitis and the insertional
      enthesopathy of the semimembranosus muscle. As for lateral syndromes, the
      phlogistic involvement of the distal insertional tract of the broad fascia tensor
      tendon with bursa reaction is very frequently reported, while the inflammation of
      the popliteal tendon and of the femoral bicipital tendon is less common.
      CONCLUSIONS: Although less frequent than meniscal and ligament injuries,
      impingement syndromes must be taken into due consideration when looking for knee
      disorders resorting to different diagnosis methods. Diagnostic imaging is very
      useful in this regard as it allows a proper and correct diagnosis procedure for
      any single condition.

PMID- 9652504
TI  - Ankle impingement syndromes.
AB  - The ankle impingement syndrome is a frequent condition in both athletes and the
      normal population. We investigated this painful syndrome from both a clinical and
      a diagnostic viewpoint. Depending on what ankle tissue impinges on the other, it
      is possible to distinguish bone impingement, soft tissue impingement and
      peripheral nerve entrapment. For each of these pathologic conditions we
      investigated the diagnostic role of conventional radiography, Computed Tomography
      and Magnetic Resonance Imaging. The evidence of osteophytes, exostosis and
      presence of the os trigonum on plain films make clinical diagnosis easy in both
      anterior and posterior bone impingement. CT can provide useful information about
      the component of the posterior ankle. MRI always adds important information about
      chondral or subchondral bone injuries, synovial reaction and adjacent soft tissue
      involvement. The anterolateral impingement syndrome is caused by repeated
      injuries in plantar flexion and ankle intrarotation. MRI well detects the
      meniscoid injury thanks to high contrast sequences; it can also distinguish this
      syndrome from painful chondral and/or bony lesions at this level. MRI is also the
      method of choice to study sinus tarsi impingement, especially thanks to fat
      suppression sequences which increase MR diagnostic capabilities in this important
      anatomic area. Deep peroneal nerve entrapment, the medial plantar nerve
      entrapment syndrome and the tarsal tunnel syndrome are the most important
      entrapment neuropathies of the ankle. US and MRI are very useful to study the
      tendon and soft tissue abnormalities causing the anterior tarsal tunnel syndrome.
      CT and particularly MRI can easily detect many pathologic conditions causing the
      medial plantar nerve entrapment and the tarsal tunnel syndromes.

PMID- 9652505
TI  - Classification of bone tumors.
AB  - The classification of bone tumors relies on the cytologic features and products
      of tumor cells. This classification is reproducible and accepted by pathologists,
      oncologic surgeons and oncologists. Chondrogenic tumors are the second largest
      group of bone tumors. Their histologic pattern suggests a relationship to hyaline
      cartilage. Exostoses, or osteochondromas, represent about 1/3 of chondrogenic
      lesions. Chondromas are hyaline cartilage tumors which can be found centrally or
      subperiosteally; they may contain some calcifications and/or ossifications.
      Chondroblastomas are tumors whose cells produce, at least focally, a matrix
      similar to hyaline cartilage. Histology of chondromyxoid fibromas shows large or
      small areas where proliferating cells produce a matrix resembling the hyaline
      cartilage. Chondosarcomas are tumors whose malignant cells produce a
      cartilaginous matrix. Most of them occur in previously normal bones; they are
      classified as conventional or primary chondrosarcomas. Secondary chondrosarcomas
      result from the malignant transformation of a benign cartilaginous lesion less
      commonly enchondromas and most commonly osteocartilaginous exostoses, or
      osteochondromas. Less common variants include dedifferentiated, mesenchymal and
      clear cell chondrosarcomas. Osteogenic tumors are the third largest group of bone
      tumors, with osteosarcomas being the most frequent type. The most important
      criterion for a tumor to be considered an osteosarcoma is that the malignant
      tumor cells must produce a recognizable osteoid matrix, at least focally.
      Osteosarcomas are divided into three groups: osteoblastic, chondroblastic and
      fibroblastic, according to the dominant histologic feature. Osteosarcomas can be
      multifocal, synchronous or metachronous; they are also classified by the
      histologic grade of malignancy. Pathologically low grade lesions, which are
      clinically indolent, are generally known as low grade central and parosteal
      osteosarcomas.

PMID- 9652506
TI  - The current role of radiography in the assessment of skeletal tumors and tumor
      like lesions.
AB  - Radiography offers more information than any other imaging modality in the study
      of bone lesions and remains the cornerstone for the differential diagnosis of
      skeletal tumors and tumor-like lesions thanks to its higher specificity in
      detecting tumor morphologic hallmarks. the radiographic features that help the
      radiologist make the diagnosis of a bone tumor or tumor-like lesion, or at least
      narrow the diagnostic possibilities, include patterns of bone destruction
      (geographic, moth-eaten and permeated), lesion margins (from sclerotic rim to ill
      defined margin), internal characteristics of the lesion (non-matrix producing
      tumors, non-mineralized matrix producing tumors, mineralized matrix producing
      tumors), type of host bone response (medullary or periosteal), location (femur,
      tibia, humerus, etc.), site (metaphysis, diaphysis or epiphysis), and position
      (central, eccentric or periosteal) of the lesion in the skeletal system and in
      the individual bone, soft tissue involvement, and single or multiple lesion
      nature. Patterns of bone destruction, margins, and reactive changes in the host
      bone clearly depict the growth rate of a bone lesion, that is its biologic
      activity; the matrix of the lesion, as well as lesion location, site and position
      may allow a specific diagnosis. This general information coupled with clinical
      information helps define whether the lesion is neoplastic or non-neoplastic,
      benign or malignant, primary or metastatic, and will help further direct the
      subsequent work-up. CT may be indicated for the optimal assessment of tumor
      matrix especially in complex anatomical sites, such as the spine, pelvis and
      hindfoot. The main role of MRI lies in local tumor staging, especially for
      planning limb-salving resections. Biopsy is the definitive diagnostic procedure
      and should be carried out only after the appropriate diagnostic and staging
      tests. Whenever a bone lesion is suspected, clinical-radiologic pathologic
      correlation is essential to make a more accurate diagnosis and to improve patient
      care.

PMID- 9652507
TI  - Diagnostic imaging of malignant cartilage tumors.
AB  - We compared the diagnostic capabilities of CT and MRI in the study of malignant
      cartilage tumors. Information about the characterization and the intra
      /extraosseous spread of these lesions is of primary importance in the
      preoperative planning. Besides peripheral chondrosarcomas, arising from an
      osteochondroma and central chondrosarcomas, which are the most common malignant
      cartilaginous tumors, we also considered secondary, periosteal, dedifferentiated,
      clear cells and mesenchymal chondrosarcomas. Our study was performed using a
      standard MRI and CT protocol; in some cases, the examination was completed by the
      intravenous administration of a contrast agent. High contrast T2-weighted GE
      images can perfectly depict and differentiate the cartilage cap of an
      osteochondroma from the adjacent soft tissues. Evaluation of the growth of
      exostosis and of the thickness of its cap is essential in the assessement of
      malignant transformation. Both CT and MRI provide important information about
      peculiar aspects of the cartilaginous matrix such as the shape of calcifications
      ossifications and lobulated growth, septa, septal enchancement and necrotic
      intratumoral areas, furthermore, CT perfectly shows the patterns of bone
      destruction. MRI should be considered as the most reliable imaging technique for
      the locoregional staging of malignant bone tumors thanks to its spatial and
      contrast resolution. CT plays a major role in the characterization of most bone
      tumors, especially those with a cartilaginous matrix.

PMID- 9652509
TI  - Malignant tumors of the osteogenic matrix.
AB  - This article focuses on major clinical and imaging features that are of practical
      interest in the diagnosis and management of osteosarcoma, a malignant tumor
      arising from the osteogenic matrix. The current histologic classification of this
      tumor is also reported. Different types of osteosarcoma are described, each of
      them with a definite clinical and radiographic pattern. Conventional radiography
      is the keystone to diagnosis because it allows analysis of the patterns relevant
      to the different lesions (location, site, bone destruction, periostal reaction,
      soft tissue masses). The most common type of osteosarcoma is defined classic or
      conventional high grade (75%) and it typically involves the medullary cavity.
      Radiographically, it may be predominantly osteosclerotic or osteolytic, but more
      frequently it has a mixed (osteoslerotic/osteolytic) pattern. The teleangiectatic
      osteosarcoma is an aggressive form (5%) characterized by marked vascularization
      with large blood-filled cystic cavities; its typical radiographic pattern is
      purely osteolytic. Juxtacortical osteosarcoma (8-10%) indicates a group of
      osteosarcomas apparently arising on bone surface. The most common type is
      parosteal osteosarcoma which affects older subjects and has a better prognosis
      than the classic type. Radiography shows a heavily ossified mass with a broad
      base attached to the underlying cortex. CT and MRI are useful in the differential
      diagnosis of osteosarcoma and myositis ossificans or osteocondroma. Rare types of
      osteosarcoma include the periosteal and high-grade surface variants, as well as
      secondary and multifocal osteosarcoma (osteosarcomatosis). CT and MRI are the
      imaging procedures of choice in locoregional staging (intraosseous and
      extraosseous spread, skip metastases, growth plate and articular involvement). CT
      of the chest is a useful tool for detecting lung metastases. Also MRI has a role
      in monitoring the response to chemotherapy and in detecting recurrence. It
      permits a more accurate study of the tumor volume than other imaging techniques
      and clinical examination. MRI becomes even more useful when paramagnetic contrast
      agents are administered because dynamic MRI with contrast enhancement help
      differentiate postchemotherapy changes from viable tumor--the latter enhancing
      rapidly and the former slowly. Thus, dynamic MRI allows a precise mapping of any
      residual tumor activity.

PMID- 9652508
TI  - Skeletal benign bone-forming lesions.
AB  - The imaging features of benign osseous lesions of the bone are often
      characteristic and suggestive of a specific diagnosis. This is particularly true
      for skeletal benign bone-forming lesions such as enostosis, osteoma, osteoid
      osteoma and osteoblastoma. Enostosis or bone island is an incidental finding in
      the axial skeleton (pelvis, spine, ribs) of asymptomatic patients; it appears as
      a small (0.2-2 cm) round to oval sclerotic area with irregular, radiating
      ('thorny') spicules peripherally. Osteoma is a benign slow-growth tumor and
      usually an incidental finding in cranial sinuses, vault and mandible, and
      presenting as a homogeneous, sharply defined bone mass arising from bone surface;
      its signs and symptoms are rare and depend on the tumor size and location--e.g.
      sinusitis, headache, exophthalmos, diplopia. Osteoid osteoma is a painful highly
      vascularized benign tumor usually affecting the long bone diaphysis cortex of
      young patients; it generally appears as a small radiolucent nidus with or without
      central calcification and surrounding bone sclerosis on radiographs, and as a
      'hot' spot on scintigraphy. CT is the method of choice for the definite location
      of the nidus especially in sites of complex anatomy, such as the spine, pelvis
      and hindfoot. Osteoblastoma is a rare tumor, histologically similar to osteoid
      osteoma but with a significantly different clinical potential because of the
      possibilities of postoperative recurrence, of its locally aggressive behavior or,
      rarer still, malignant transformation; the spine and long bones are affected in
      more than half the cases. Its radiologic appearance is not always distinctive and
      usually characterized by a lytic lesion with varying bone production and
      expansile behavior; CT and MRI are required for the diagnosis of spinal
      osteoblastomas. When a bone-producing tumor or tumor-like lesion is suspected but
      no specific diagnosis can be made, the knowledge of the range of the imaging
      findings of these lesions will allow a suitably ordered differential diagnosis.
      Radiography is the single most effective imaging method in this respect. CT is
      required for the tumors in complex anatomical sites, such as the spine, pelvis
      and hindfoot, as well as for the optimal assessment of the tumor matrix. MRI is
      specifically required to study the lesion effect on the spinal canal.

PMID- 9652510
TI  - Semeiotics of bone tumors in children.
AB  - In recent years, the study of bone disorders has changed thanks to the
      progressive development of imaging techniques. In our opinion, however, different
      from what happens in the study of pathologic conditions in other organs and
      systems, conventional radiology remains the diagnostic cornerstone for bone
      disorders and especially bone tumors. In any case, plain radiography must always
      be performed first. The radiologic approach to primary bone tumors includes a
      series of steps to collect the necessary information to suggest, with the
      following contribution of radiography, the most likely diagnosis. The approach is
      basically statistical and many parameters should be considered. As far as bone
      tumors in children are concerned, the basic role of the statistical variable
      'patient age' is apparent and this information should be considered even before
      any others. Despite the difficulties in assessing the frequency of bone tumors we
      tried to read homogeneously some of the statistical data reported in literature.
      Tumor incidence in a given age class is a very important diagnostic tool. Lesion
      location is the second step in the radiologic work-up: the involved bone and bone
      segment should be assessed and correlated with the preferential site of a
      specific tumor. Regarding the bone tumors detected in the first 5 years of life,
      an interesting question is whether a vertebra plana is due to a benign or a
      malignant lesion. The lytic lesion will be well defined by CT and MRI will be
      very useful in depicting bone marrow and surrounding soft tissue involvement.
      However, many processes have a similar imaging pattern. We believe that before
      biopsy the frequent, marked infiltration of surrounding soft tissues in vertebra
      plana should suggest a diagnosis of malignant tumor rather than of tumor-like
      lesion.

PMID- 9652511
TI  - The value of imaging in the diagnosis and treatment of bone tumors.
AB  - The authors report their experience in the diagnosis of bone tumors at the
      Rizzoli Institute of Bologna. The main imaging techniques used to this purpose
      are conventional radiography, CT, MRI, and isotope bone scan. Angiography is
      rarely used. Conventional radiography is the examination of choice and is
      sufficient in several benign lesions not requiring treatment. Supplementary
      imaging studies are usually needed when radiographic findings are questionable
      and/or the lesion requires treatment. When a biopsy is required, it should be
      carried out after a complete imaging work-up, which sometimes allows a correct
      prebiopsy diagnosis, indicates the biopsy modality, approach and site, and is
      also mandatory to stage the tumor, plan the surgical approach and technique, and
      show in the finest details the occult tumor spread. CT best shows mineralized
      tissues and pulmonary metastases. It is also frequently used as a guide for
      needle biopsies. MRI beautifully shows the different tissues and compartments and
      it is particularly sensitive in depicting fat. Moreover, it can be repeated many
      times, even in pregnant women, because it needs no ionizing radiations and
      iodinated contrast; it is also free of artifacts in the patients with orthopedic
      devices which are usually nonferromagnetic. However, the execution of an adequate
      MRI requires experience and knowledge of bone pathologic conditions. Bone scan
      helps in detecting any 'active' area in the bone. It can be thus useful to depict
      lesion quiescence or activity and to stage any tumor which can metastasize to the
      skeleton. Bone scan is also helpful to show bone lesions when they are not
      visible on plain radiographs and indicates the tumor response to preoperative
      chemotherapy. Angiography is helpful when a preoperative selective embolization
      is needed, or when complex vertebral surgery or vascular surgery are planned. The
      bad outcome of bone tumors often depends on incomplete, inadequate or
      misinterpretated imaging findings.

PMID- 9652512
TI  - Nuclear medicine in primary bone tumors.
AB  - INTRODUCTION: Conventional radiography is the method of choice to diagnose a
      primary bone tumor but in many cases it is necessary to integrate it with nuclear
      medicine scintigraphy using several radionuclides, including 67Ga, 201Tl, 99mTc
      MIBI and especially 99mTc-diphosphonates. Recently a new technique has been
      recently introduced, that is positron emission tomography with 2(18F) fluoro-2
      deoxy-D-glucose as radiopharmaceutical. OBJECTIVE: The specific purpose of this
      work is to show that nuclear medicine bone scanning is a very important method in
      the detection and diagnostic management of primary bone tumors. DIAGNOSIS,
      STAGING AND FOLLOW-UP: Three-phase bone scintigraphy, integrated with SPECT, is
      clinically useful to confirm the radiologic diagnosis of bone tumor. These
      techniques conveniently related to each other and to radiographic findings, can
      evaluate the tumor's local aggressiveness, often differentiating benign from
      malignant lesions, to monitor treatment efficacy, to permit total body scanning
      for the detection of recurrences. Nuclear medicine diagnostic techniques are not
      in competition with radiographic tools as CT and MRI which are highly sensitive
      in detecting even small lesions thanks to their excellent anatomical resolution.
      In questionable cases, we can integrate radiologic imaging with dynamic studies,
      in particular with FDG-PET, increasing the specificity of diagnosis and
      permitting more accurate follow-up. CONCLUSIONS: Patient management optimization
      needs the integration between dynamic nuclear medicine findings and the
      anatomical patterns provided by conventional radiology to increase imaging
      sensitivity and specificity. Equipe work is determinant to customize the
      diagnostic work-up to the individual patient's needs to reduce the cost of
      patient management avoiding useless examinations.

PMID- 9652513
TI  - Power Doppler sonography: clinical applications.
AB  - OBJECTIVE: Color Doppler imaging (CD) has had a great impact on ultrasonography
      (US). This technique depicts local flow by encoding an estimate of the mean
      Doppler frequency shift at a particular position in color. However, the choice of
      the mean frequency shift as the parameter for representing flow in color Doppler
      is somewhat arbitrary. Power Doppler ultrasound is a technique that encodes the
      power in the Doppler signal in color. This parameter is fundamentally different
      from the mean frequency shift. The frequency is determined by the velocity of the
      red blood cells, while the power depends on the amount of blood present.
      Providing an image of a different property of blood flow, power Doppler has shown
      several key advantages over colour Doppler, including higher sensitivity to flow,
      better edge definition and depiction of continuity of flow. In this paper we
      review the results of power Doppler clinical studies. MATERIALS AND METHODS: All
      relevant information available in the literature on the potential clinical
      applications of this technique was revised to give a detailed survey. RESULTS:
      The increased flow sensitivity and better vascular detailing of power Doppler
      have been used to detect flow presence and characteristics in vessels that are
      poorly imaged with conventional color Doppler. The improved depiction of tissue
      vasculature has shown potential advantages, especially in some areas, such as the
      cortex of native kidneys and renal allografts, the prepuberal testis, the infant
      hip and the bowel wall, in which color Doppler is not sensitive enough to detect
      clinically important, slow and poor flow in small vessels. In inflammatory
      conditions, power Doppler was valuable in depicting increased flow in vessels
      that are dilated because of inflammatory response. In this field, advantages have
      been reported in acute cholecystitis and in inflammatory states of
      musculoskeletal tissues. The higher sensitivity to slow flow and the improved
      detailing of the course of tortuous and irregular vessels made power Doppler a
      promising technique to image intratumoral vessels and, thereby, to ameliorate the
      accuracy of color Doppler in predicting the likelihood of benign versus malignant
      nature of nodules. Specific flow patterns, missed at color Doppler studies, have
      been indicated with power Doppler in some tumors of the liver and breast. In
      different settings, power Doppler also permitted to monitor serial blood flow
      changes after therapy and to display them as color intensity, allowing the
      observer to distinguish flow changes. CONCLUSION: Although the actual role of
      power Doppler in changing patient management has not been assessed yet, this
      technique can depict flow which was previously undetectable, and thus permits an
      easier and more confident diagnosis in body regions where the ultrasound signal
      is weak because blood vessels are small.

PMID- 9652514
TI  - Transcranial Doppler: state of the art.
AB  - INTRODUCTION: Transcranial color Doppler sonography permits the accurate
      assessment of intracranial arteries. The latest Doppler units, using the color
      and power techniques, can show even very small flow volumes (1 x 1 mm). Low
      frequency (2-2.5 MHz) and very focused transducers are used in transcranial color
      Doppler. The skull is a very strong barrier for ultrasounds, which requires the
      use of some acoustic windows like some thin portions of the skull bone or some
      natural skull foramina. The use of echocontrast agents in color Doppler seems to
      increase the applications of transcranial studies. OBJECTIVE: (1) To report on
      transcranial color Doppler technique and findings. (2) To assess the role of
      contrast agents in the visualization of intracranial vessels. (3) To define the
      main indications of this technique. MATERIAL AND METHODS: The temporal, the
      orbital and the suboccipital are the main acoustic windows used for transcranial
      color Doppler studies. We use phased-array transducers (2-2.5 MHz) and,
      preferrably, the echocontrast agent. We examined 15 patients with severe internal
      carotid artery stenoses after the infusion of Levovist (Schering AG, Berlin,
      Germany) suspension (8 ml at 300 mg Galactose/ml, infused at 0.5 ml/s). RESULTS:
      Levovist infusion permitted to depict the main intracranial vessels in all cases.
      The middle and the anterior cerebral arteries are shown through the temporal
      window. The former is the main cerebral artery, it is the easiest to identify and
      presents the highest peak systolic velocity. The orbital window can be used to
      visualize the ophthalmic artery and the internal carotid artery siphon, while the
      vertebral and the basilar arteries are demonstrated through the suboccipital
      window. DISCUSSION: We report the most important findings and discuss the main
      indications of transcranial color Doppler studies. In addition to flow presence
      and direction, the main indices of arterial flow can be measured thanks to
      contrast agent administration, namely the peak systolic velocity, the end
      diastolic velocity, the resistance index and the pulsatility index. A
      morphological assessment of the Willis circle can also be carried out with color
      and power Doppler. Functional studies can be performed to assess the residual
      autoregulatory function of the cerebral circle in the patients with internal
      carotid artery stenosis or occlusion. The development of intracranial collateral
      circles can also be studied in these patients. Moreover, the M1 segment of the
      middle cerebral artery and the internal carotid artery siphon can be demonstrated
      directly. Transcranial color Doppler is also a useful tool to detect vasospasm
      after subarachnoid hemorrhage and to monitor blood flow velocity in the middle
      cerebral artery during carotid endarterectomy. The assessment of blood supply to
      arteriovenous malformations and to intracranial neoplasms is another application.
      CONCLUSION: With reference to internal carotid stenoses, the main applications of
      transcranial color Doppler are the study of intracranial vessels, of intracranial
      arterial stenosis, of arteriovenous malformations and of Willis circle aneurysms,
      as well as the monitoring of blood flow velocity during carotid endarterectomy.
      Echocontrast agents play an important role in the visualization of intracranial
      vessels.

PMID- 9652515
TI  - Monitoring treatment response with color and power Doppler.
AB  - Color and power Doppler are now widely used to monitor treatment response because
      of the latest technologic advances and of the increasing use of echo-enhancing
      agents. The assessment of treatment response is based on the amount of necrosis
      obtained and changes in local vascularization indicate a successful treatment. To
      date, clinical experiences have mainly concerned the treatment of hepatocellular
      carcinomas, hyperfunctioning nodules of the thyroid and parathyroid glands and
      the neoadjuvant chemotherapy of breast cancer. Aim of this review is to describe
      the role and potentials of color and power Doppler in this field. Hepatocellular
      carcinomas are currently treated with surgery or percutaneous ethanol injection
      and/or chemoembolization. Treatment response can be monitored with color Doppler:
      after a successful treatment, color signals are no longer detectable on color
      Doppler images. Conversely, the presence of arterial signals indicates persistent
      viable tumor. Unfortunately, color Doppler is limited when the hepatocellular
      carcinoma is hypovascular, small or deep. Echo-enhancing agents may help overcome
      these limitations, although spiral computed tomography or dynamic magnetic
      resonance imaging cannot be replaced yet in the definitive assessment of tumor
      necrosis. Color and power Doppler are well-established tools in the study of
      functioning thyroid and parathyroid adenomas after percutaneous ethanol
      injection. Echo-enhancing agents may improve Doppler sensitivity in the detection
      of residual viable tissue. Other interesting applications of color and power
      Doppler in this field are secondary hyperparathyroidism and hyperfunctioning
      thyreopathies (Graves' disease) treated with mercaptoimidazole. The evaluation of
      systolic flow velocity in the inferior thyroid artery is more reliable than the
      quantitative analysis of color signals in monitoring treatment response in
      Graves' disease. In our experience, systolic velocity in the inferior thyroid
      artery decreased from 150-250 to 60-80 cm/s after medical therapy. Finally,
      Doppler studies have provided good results in the follow-up of breast cancers
      after neoadjuvant therapy. In our experience on 18 patients treated with local
      parenteral repeated administration of antiblastic drugs, sonography showed no
      more signals within the lesion in 16 patients at the end of therapy. In the
      remaining two cases with persistent tumor at ultrasound, some color spots were
      still present and histopathology confirmed residual tumor cells. In conclusion,
      the results of color and power Doppler are encouraging. Thus, we believe that
      Doppler will be increasingly used in monitoring treatment response.

PMID- 9652516
TI  - Ultrasound contrast agents: basic principles.
AB  - INTRODUCTION: Ultrasonography lacked substances to be administered to patients to
      improve or increase the diagnostic yield, which is peculiar considering that
      contrast agents have long been used with all the other imaging techniques.
      Fortunately some contrast agents, most of them consisting in gas microbubbles,
      have been recently introduced for ultrasound imaging too: this review will focus
      on their history, behavior, current applications and future developments.
      Echocontrast agent research is in progress and many new agents are expected to be
      marketed this and next year, to be added to Levovist by Schering AG (Berlin,
      Germany), to enhance the ultrasound signal safely and effectively. No definitive
      conclusions can be drawn yet on the actual merits of each contrast agent, but all
      of them seem to be both effective and safe, meaning that their future success
      will depend on the relative cost-effectiveness and peculiarities. THE BASIC
      PRINCIPLES OF ECHOCONTRAST AGENTS: The microbubbles act as echo-enhancers by
      basically the same mechanism as that determining echo-scattering in all the other
      cases of diagnostic ultrasound, namely that the backscattering echo intensity is
      proportional to the change in acoustic impedance between the blood and the gas
      making the bubbles. The different acoustic impedance at this interface is very
      high and in fact all of the incident sound is reflected, even though not all of
      it will of course go back to the transducer. But the acoustic wave reflection,
      though nearly complete, would not be sufficient to determine a strong US
      enhancement because the microbubbles are very small and are sparse in the
      circulation. Moreover, reflectivity is proportional to the fourth power of a
      particle diameter but also directly proportional to the concentration of the
      particles themselves. SECOND HARMONIC IMAGING: As we said above, the microbubbles
      reached by an ultrasound signal resonate with a specific frequency depending on
      microbubble diameter. However, the main resonance frequency is not the only
      resonance frequency of the bubble itself and multiple frequencies of the
      fundamental one are emitted, just like in a musical instrument. These harmonic
      frequencies have decreasing intensity, but the second frequency, known as the
      second harmonic, is still strong enough to be used for diagnostic purposes. The
      theoretical advantage of the harmonic over the fundamental frequency is that only
      contrast agent microbubbles resonate with harmonic frequencies, while adjacent
      tissues do not resonate, or else their harmonic resonation is very little. Thus,
      using a unit especially set to produce ultrasounds at a given frequency (3.5 MHz)
      and receive an ultrasound signal twice as powerful (7 MHz) it will be possible to
      show the contrast agent only, without any artifact from the surrounding
      anatomical structures, with a markedly improved signal-to-noise ratio. A similar
      effect to digital subtraction in angiography can thus be obtained, even though
      through a totally different process. Moreover, second harmonic imaging permits to
      show extremely small vessels (down to 40 microm) with very slow flow, which would
      be missed with a conventional method. B-mode imaging can also depict the
      microbubbles in the myocardium suppressing nearly all the artifacts from cardiac
      muscle motion. Recently a peculiar behavior of microbubbles has been observed
      which may permit contrast agent detection even in capillaries. This method is
      variously known as sonoscintigraphy, loss of correlation, stimulated acoustic
      emission and transient scattering. The contrast agent microbubbles reached by an
      ultrasound beam powerful enough explode producing a strong and very short
      backscatter echo which is read by the unit as a Doppler signal and results in a
      color pixel where the individual microbubble exploded. CONCLUSIONS: The
      microbubble contrast agents developed and introduced as safe and effective echo
      enhancers in present-day clinical practice will open up new oppurtunities

PMID- 9652517
TI  - Contrast enhancing agents in ultrasonography: clinical applications.
AB  - INTRODUCTION: As ultrasound remains a poorly sensitive method, echocontrast
      agents make a real difference. At least 29 echocontrast agents are currently on
      trial worldwide; their chemical composition, mechanisms of action and possible
      clinical applications are different. The state of the art of echocontrast agents
      is discussed: their established applications, those expected in the near future
      and finally their hypothetical, ideal applications. POTENTIAL CLINICAL
      APPLICATIONS: An extravascular and a vascular domain can be considered. The
      former includes the gastrointestinal tract and body cavities--both the normal
      (bladder, uterus, tubes and so on) and the abnormal (abscesses, fistulas,
      pericardium, peritoneum and so on) ones. Echocontrast agents can: (1) create or
      improve an acoustic window; (2) distend some organs and fill them with a liquid,
      with homogenous attenuation of the ultrasound beam; (3) displace the air
      containing intestinal loops; (4) depict the walls, the shape and the contours of
      a normal or abnormal cavity; (5) detect abnormal communications, fistulas and
      drainages; and (6) evaluate the amount of fluid in the pleural, pericardial or
      peritoneal cavities. As for vascular applications, this domain sees the highest
      number of echocontrast agents on trial or on the market. The best know of them
      are: Levovist (Schering AG, Berlin, Germany), BR1 (Bracco, Milan, Italy) and
      EchoGen (Abbott, USA). All these act by enhancing arteries, veins and
      capillaries. The clinical applications validated in clinical trials mainly regard
      studies in intracranial and neck vessels and the vascularity of upper and
      especially lower limbs of renal vessels. Tumor macrovascularity (and in the
      future, hopefully microvascularity) can also be studied in parenchymatous and/or
      glandular organs, as well as in intra- and extra-abdominal parenchymatous organs
      in the periskeletal soft tissues. Clinical validation has also been obtained in
      the follow-up of tumors submitted to ablation therapy (chemoembolization, ethanol
      injection, thermal ablation) and in echocardiography, both for morphological
      studies in the cardiac cavities and for the cardiac wall perfusion. CONCLUSIONS:
      In a subgroup of 513 out of 1275 patients examined Europe-wide, the contrast
      agent Levovist increased the diagnostic confidence from 27.4 +/- 22.5 to 77.2 +/-
      22.5%. Such data encourage further trials to validate current preliminary
      results.

PMID- 9652518
TI  - New prospects for ultrasound contrast agents.
AB  - Considering the several suggestions regarding the future developments of
      echocontrast agents, there is a striking difference between the few compounds
      actually available on the market and used in clinical practice and those
      undergoing experimental clinical trials. It is therefore difficult to predict
      what will be the actual impact of these agents in the next future. Future
      developments will probably go beyond color enhancement which was the end-point
      till a very short time ago. They can be schematically summarized as follows: (1)
      development of new substances which enhance both color and gray scales; (2) use
      of new-generation substances, such as BR1 (Bracco, Milan, Italy) and EchoGen
      (Sonus, Bothell, WA), which use a gas other than air, such as perfluorate
      compounds which are more stable and guarantee longer and stronger effects; (3)
      use of more complex compounds acting at different levels. For example, SHU 536A
      (Sonovist) produces resonance phenomena with the second and third harmonics, and
      also stimulated acoustic emission which permits the morphological study of liver
      parenchyma. Other promising compounds are liposomes and aerosomes. Among the new
      possibilities in recording and observing phenomena, we can distinguish two main
      application fields: one is based on the physics of ultrasound and related to the
      presence of microbubbles in an acoustic field. These phenomena are generally
      obtained increasing the emission acoustic pressure, which eventually results in
      microbubble destruction and they are called nonlinear because there is no direct
      relationship between emission and return frequencies. These phenomena, which are
      detectable only with dedicated equipment, include: the resonance phenomenon with
      harmonic emission; intermittent harmonic emission and stimulated acoustic
      emission. The other application field is not strictly related to ultrasound
      physics and includes all the systems which can detect the presence of microbubles
      qualitatively or quantitatively. Other possible applications are related to the
      possibility of acquiring not only morphological but also functional data,
      especially in cardiology and neurology. Finally, targeted agents are potentially
      capable of demonstrating receptor sites or specific molecules, which may open
      very interesting therapeutic routes.

PMID- 9652519
TI  - The latest in ultrasound: three-dimensional imaging. Part 1.
AB  - OBJECTIVE: The state-of-the-art of three-dimensional ultrasound is reviewed to
      evaluate technological achievements and future possibilities in diagnosis and in
      the follow-up of medical or invasive therapy. MATERIAL AND METHODS: The problems
      related to volumetric acquisitions in the tissues of interest to provide three
      dimensional images are considered. Three-dimensional images are easier to achieve
      with computed tomography because the scanning system of this technique is
      automatic and thus provides sequential slices. The same is true for magnetic
      resonance imaging which can aquire volumes directly. The problem with ultrasound
      lies in the fact that the scans are manual and therefore less precise. To obtain
      three-dimensional images these devices are commonly used: manual scanning probes
      connected to spatial magnetic evidencers with remote processing; manual scanning
      probes connected to spatial magnetic evidencers placed on the patient's
      examination table with processing internal to the ultrasound unit; mechanical
      probes that can provide volumetric scans; 'matrix' probes. Recent contributions
      are discussed relative to three-dimensional applications to cardiology (cardiac
      valve studies), obstetrics (malformations), gynecology (uterine malformations and
      extensive ovarian disease studies), gastroenterology (diagnosis of pancreatic and
      hepatoabiliary tumor extent), uro-nephrology (detection of stones, prostatic
      tumors) and finally in the study of rectal carcinomas. CONCLUSIONS: Nearly all
      the papers about three-dimensional ultrasound are works in progress because the
      technique has not been standardized yet and some of its future diagnostic
      possiblities are difficult to foresee. Moreover, 'matrix' probes are still in the
      experimental stage. Nevertheless, this technique seems to be able to yield the
      best results in: fetal malformations; calculating the volumes of normal and
      diseased organs; the follow-up of masses treated with irradiation/chemotherapy or
      with alcohol or chemoembolization; the spatial reconstruction of extensive
      lesions; the detection of small lesions (metastases); the study of some complex
      functions such as cardiac valve dynamics. But the real problem with three
      dimensional sonography is not its efficiency but rather its efficacy, that is
      which actual role this technique can play in diagnosis and which information it
      can add to that obtained with two-dimensional imaging.

PMID- 9652520
TI  - The latest in ultrasound: three-dimensional imaging. Part II.
AB  - INTRODUCTION: The three-dimensional (3D) reconstruction of ultrasound images has
      become a widespread option in ultrasound equipment. Specific softwares have
      become available and 3D reconstruction feasible since the early 1990s,
      particularly since 1994. POSSIBLE CLINICAL APPLICATIONS: Several clinical
      applications are feasible in all parenchymatous organs (mainly the liver and
      prostate), hollow viscera (e.g. the bladder and gallbladder), peripheral vessels
      (supra-aortic trunks and limb vessels) and central (the aorta and iliac arteries)
      or cerebral vessels. Moreover, tumoral vessels in parenchymatous organs can be
      reconstructed, and even the fetus in the uterine cavity, with excellent
      detailing. The recent introduction of echocontrast agents and second harmonic
      imaging has permitted to study normal and abnormal peripheral, central and
      parenchymatous vessels, with similar patterns to those obtained with digital
      angiography. The spatial relationships between the vascular structures of the
      liver, kidney and placenta were studied with 3D ultrasound angiograms. The
      applications of this new technique include the analysis of vascular anatomy and
      the potential assessment of organ perfusion. THE LATEST APPLICATIONS-
      INTRAVASCULAR STUDIES: Some catheters with an ultrasound transducer in the tip
      have been tested for intravascular studies. Just like conventional transducers,
      they provide two-dimensional (2D) images which are then postprocessed into
      longitudinal 3D or volume reconstructions. The former resemble angiographic
      images and can be viewed 3D rotating the image along its longitudinal axis.
      Volume images, which are more complex and slower to obtain, can be rotated on any
      spatial plane and provide rich detailing of the internal vascular lumen. The
      clinical importance of intravascular ultrasound with 3D volume reconstructions
      lies in the diagnosis of vascular conditions and the assessment and monitoring of
      intravascular interventional procedures--e.g. to detect inaccurate deployment of
      intravascular stents and endoluminal grafts during the maneuver. Three
      dimensional reconstructions involve geometric data assembly and volumetric
      interpolation of a spatially related sequence of tomographic cross sections
      generated by an ultrasound catheter withdrawn at a constant rate through a
      vascular segment of interest, resulting in the display of a straight segment.
      Therefore particular care is needed and there are some useful hints to avoid
      mistakes. CONCLUSIONS: Three dimensional reconstructions of B-mode and color
      Doppler images are no longer a work in progress and their clinical importance and
      possible applications are both established and ever-increasing. On the other
      hand, independent of the different types of energy used, also computed tomography
      and magnetic resonance 3D reconstructions are very useful from a clinical
      viewpoint and they have become an established routine technique for both these
      methods. It is very likely that 3D volume reconstructions in ultrasound will find
      numerous applications in the near future. They may help to increase the
      diagnostic confidence and to facilitate diagnosis, intraprocedure monitoring in
      interventional radiology and follow-up and also to reduce the number of invasive
      examinations with iodinated contrast agents. This could result in cutting the
      cost and duration of the most expensive examinations. New, although invasive,
      applications can be hypothesized for intravascular or intraluminal catheters with
      an ultrasound transducer inside.

PMID- 9652521
TI  - Ultrasound transducers.
AB  - Sonography is facing a new technological revolution. Recent advances in
      ultrasound technology are increasing spatial, contrast and vascular resolution.
      Transducers play an important role in achieving these improvements; their
      technology is widely reviewed in this paper. Physics and technology relate to
      image quality and its clinical potentials. Large annular arrays made the
      progression of imaging quality; they are still a very good choice for scanning
      superficial structures. New broadband linear arrays approach their quality and
      allow to visualize the flow within very small vessels; they permit new harmonic
      imaging that reduces image noise and clutter caused by the body wall. New
      advances include digital beamformers that work at their best when coupled with
      broadband technology. New multi-layer and multi-array scanheads improve the
      signal-to-noise ratio and increase the transmitted energy. New transducers and
      imaging algorithms allow real-time acquisition of large fields of view and even
      of three-dimensional volumes. Further refinement of two-dimensional matrix
      transducers will produce high-definition volumetric images. Evolution in
      transducers technology permits to interrogate the vessels with higher Doppler
      frequencies extending the anatomical perception and opening new fields of
      investigation.

PMID- 9652522
TI  - Ultrasonography and PACS.
AB  - Expectations and problems related to picture archiving and communication systems
      handling of ultrasound images are discussed. Sonography has peculiarities that
      must be considered when its integration with picture archiving and communication
      systems is planned, namely: (1) data volume is about 3 Mb per ultrasound
      examination and is usually lower than that of other imaging modalities; this
      makes many requirements less strict; (2) color images represent further problems
      which can however be solved with systems capable of performing the analog-to
      digital conversion in more than 8 bits; (3) the available equipment comes
      with/without digital ports; the interfaces between the ultrasound unit picture
      archiving and communication systems are usually based on frame grabbing which
      might be sufficient for sonography; (4) equipment may be located in different
      departments or in private offices. Therefore solutions (mini-PACS limited to
      ultrasound, sub-PACS with a modular development, global PACS) are closely related
      to the environment. Our personal experience began with the installation of a
      commercial system 10 years ago. With respect to sonography, picture archiving and
      communication systems allowed a more reliable and quicker retrieval of previous
      examinations, the immediate availability of images in different sites throughout
      the hospital and to avoid filming. About 70000 ultrasound examinations have been
      archived on optical disks, with a mean of ten images per investigation. Since
      November 1991, the picture archiving and communication system has been the only
      archive where such images can be found. The location of workstations in the wards
      allows the almost real-time availability of images and the immediate availability
      of reports right after typing. A questionnaire was given to all the hospital's
      clinicians and the following advantages were pointed out: no examination
      repetition, no unnecessary investigations, shortening of hospitalization time,
      impact on treatment choices. Our experience is going on with a new project,
      DPACS, providing all the services of the former system and offering a full
      integration with RIS both in the hospital and in the city areas and allowing
      communication between DICOM and non-DICOM compliant devices.

PMID- 9652523
TI  - New applications of ultrasonography: interventional ultrasound.
AB  - Since 1975-80, worldwide but mostly in Europe and Japan, sonography has become
      the imaging technique of choice for guiding percutaneous interventional
      procedures for diagnostic or therapeutic purposes. In the last 10 years, the most
      important advances in interventional ultrasound have occurred in therapeutic
      applications, fostering and facilitating the development of the so-called
      minimally-invasive techniques. Among all these new applications for the treatment
      of fluid collections, inflammatory diseases, benign and malignant tumors, the
      most recent dramatic advances have occurred in primary and secondary liver
      malignancies, which will be the focus of this review. The rationale for the local
      treatment of primary and secondary liver cancers differs according to the success
      of conventional treatments (e.g. surgery and chemotherapy) and to the survival
      rates of such conditions, depending on clinical stage, patient age, associated
      diseases, and so on. Ultrasound-guided percutaneous therapies for liver cancer
      can be divided into: (1) direct intratumoral injection of chemical agents, such
      as ethanol, hot saline and acetic acid; and (2) thermally-mediated techniques,
      such as radiofrequency ablation, interstitial laser photocoagulation, microwave
      therapy or cryotherapy. Through different mechanisms of action, all these methods
      induce cell death by coagulative necrosis. The clinical efficacy of some of these
      techniques has been clearly established, like percutaneous ethanol injection in
      the treatment of hepatocellular carcinoma. In contrast, experience with the other
      techniques is much more preliminary, mostly due to the limited availability of
      sufficient clinical trials and to the fascinating speed of technological
      development. We review the state-of-the-art of the two most promising techniques,
      namely radiofrequency ablation and interstitial laser photocoagulation, and the
      present preliminary clinical data in the treatment of hepatocellular carcinomas
      and liver metastases. Radiofrequency energy is delivered to the tumors by means
      of electrode-needles (14-17 G) electrically insulated along all but the distal
      portion of the shaft and percutaneously introduced into the targets under
      ultrasound guidance. In the short history of this method, several technologies
      have been tested and used, but 'multiple-hook' and 'internal-cooling' electrodes
      are currently the leading choices, providing large necrosis volumes (up to 5 cm
      in diameter for a single 12-min application with an array of three internal
      cooling electrodes) in short sessions, under local or general anesthesia.
      Radiofrequency ablation has proved its usefulness in the treatment of
      hepatocellular carcinomas, achieving complete necrosis in over 85-90% of cases in
      lesions smaller than 5 cm in diameter and in single sessions, with a low rate (<
      10%) of local recurrences. In the treatment of liver metastases, whose very poor
      responsiveness to percutaneous ethanol injection and other 'chemical' therapies
      is extensively reported in the literature, radiofrequency ablation has 65-75%
      reported complete efficacy in the control of local tumor growth in lesions not
      exceeding 4 cm. Such great efficacy has been so far coupled with very low rates
      of major side-effects (< 2%), most of them requiring no surgical repair.
      Interstitial laser photocoagulation induces thermally-mediated coagulation
      through thin optic (Nd:YAG) fibers percutaneously inserted into the target under
      ultrasound guidance. Multiple fibers (beam splitters) are usually required to
      achieve a sufficiently wide necrosis volume. The reported success rate (complete
      necrosis and local control of tumor growth) ranges 45-75%) of the lesions, mostly
      liver metastates from colorectal carcinoma. An equally low rate of complications
      is reported for interstitial laser photocoagulation as for radiofrequency
      ablation, that is no more than 2-3% of cases. (ABSTRACT TRUNCATED)

PMID- 9652524
TI  - Laparoscopic and intraoperative ultrasound.
AB  - OBJECTIVE: Intraoperative ultrasound has gradually expanded in the last two
      decades to a variety of surgical specialties and has gained an established role
      in many surgical procedures. Laparoscopic and thoracoscopic ultrasound are the
      latest modes of intraoperative sonography. They have been introduced mainly to
      overcome the two major drawbacks of laparoscopy, i.e. the capability of showing
      only the surface of the organs and the lack of manual palpation of the anatomical
      structures. We review and discuss the established and the most recent
      applications of intraoperative and laparoscopic ultrasound. MATERIAL AND METHODS:
      The technology, new indications and results of intraoperative and laparoscopic
      ultrasound are reviewed. This review is based on the experience gained in our
      Institution during more than 500 surgical procedures and the analysis of the
      literature on the subject. RESULTS: The yield of intraoperative and laparoscopic
      ultrasound consists in confirming preoperative studies and acquiring new data
      which would not be available otherwise. An important role of these techniques is
      determining the anatomy of the involved organs, thus providing a guidance for
      surgery. Both techniques have an important role in surgical decision-making,
      particularly with respect to hepatic, biliary and pancreatic malignancies. In
      some series the rate of major changes in the surgical strategy can be as high as
      38%. A relatively new application of intraoperative ultrasound is the possibility
      to perform interstitial therapy of tumors at the time of the initial surgery.
      This can be useful, for example, in patients undergoing liver resection, when
      other unresectable lesions are found in a different segment or in the
      contralateral lobe. Finally, laparoscopic sonography has an important role in
      staging abdominal neoplasm, providing more information than preoperative imaging
      and laparoscopic exploration. This feature can be used to effectively stage
      gastrointestinal malignancies, pancreatic carcinoma, and abdominal lymphomas.
      CONCLUSION: The application of intraoperative ultrasound will increase in the era
      of minimally access surgery and this will be dependent not only on technical
      improvements in ultrasound technology. Indeed, it may be expected that a variety
      of open procedures will be performed with videolaparoscopic monitoring and will
      need the guidance of laparoscopic sonography. In the future, the staging of
      abdominal neoplasm may be markedly improved by laparoscopy combined with
      laparoscopic ultrasound; however a cost-benefit analysis of these techniques and
      a comparison with preoperative tests should be carried out.

PMID- 9652525
TI  - Current uses of diagnostic high-frequency US in dermatology.
AB  - OBJECTIVE: The diagnosis of most skin diseases, both focal and diffuse, has long
      relied mainly on physical examination findings. The recent introduction of
      technologically advanced ultrasound equipment using 20 MHz probes has permitted
      the specific application of ultrasound to dermatology. Accordingly, we
      investigated whether the findings at very high frequencies can represent a valid
      adjunct to clinical assessment in many skin conditions, including neoplasms,
      inflammatory states and diseases of unknown origin. MATERIALS AND METHODS: Skin
      lesions are studied using high frequency probes, which very clearly detail the
      three layers (epidermis, dermis and subcutaneous tissues) forming the normal
      skin. The choice of the probes frequency should depend mainly on the lesion
      diameters and site. Electronic 7.5-13 MHz linear probes depict flat and regular
      surfaces effectively and provide a wider field of surface vision and, therefore,
      a wider view than sectorial probes. Water bath sectorial mechanical probes with
      10-20 MHz frequency have very superficial focusing and are excellent to study
      irregular surfaces. RESULTS: High frequency ultrasound can be usefully correlated
      with clinical tests to study focal skin lesions. The diagnosis of most benign
      skin cancers is usually made on clinical bases. Ultrasound examinations are
      performed preoperatively in questionable cases. Malignant neoplasms appear at
      ultrasound as hypoechoic focal lesions, generally with no specific features in
      relation to the histologic type; nevertheless, preoperative ultrasound may play
      an important role in that it measures the thickness of cutaneous melanoma, which
      is a very important prognostic factor. In particular, 20 MHz probes permit to
      assess the depth of melanoma invasion. The sonographic evaluation of melanoma
      thickness is usually in agreement with histologic findings. 'Satellite'
      neoplastic lesions growing near the main tumor can also be revealed. Color and
      power Doppler studies may be combined with gray-scale imaging: the identification
      of abnormal intra- or peritumoral low-resistance pulsatile flow signals suggests
      the malignant nature of the cutaneous lesion. High frequency ultrasound can also
      be used to study diffuse cutaneous conditions. Among them, ultrasound can provide
      a valid morphologic representation of psoriatic skin lesions and it is also a
      noninvasive and accurate method for evaluating the therapeutic efficacy of
      antipsoriatic drugs. In scleroderma, sonographic findings vary depending on
      disease activity and the patterns vary; therefore, 20 MHz probes may also prove
      useful over the other instrumental tools to monitor the disease course and
      treatment efficacy in focal scleroderma. Other potential applications include
      allergic dermatitis, nodular erythema, dermatomyosis, sarcoidosis, lymphedema of
      the limbs and allergologic conditions. Ultrasound can also be used in monitoring
      the response to or complications of topic drugs administration, and in the follow
      up of focal burns. CONCLUSION: High frequency ultrasound can provide a reliable
      morphologic representation of skin lesions but it is also an accurate noninvasive
      tool for monitoring the therapeutic efficacy of drugs administration in focal or
      diffuse diseases. The application of high frequency studies to dermatology is
      very challenging. Indeed, the very high frequency probes up to 20 MHz currently
      available are particularly useful for reliable studies. Contrast-enhanced color
      and power doppler are very promising techniques. Advancements in technology will
      improve the correlation of clinical with high frequency ultrasound findings in
      the assessment of several skin diseases.

PMID- 9652526
TI  - Contrast media in liver sonography: correlation with enhanced dynamic magnetic
      resonance imaging.
AB  - Both color Doppler sonography and magnetic resonance are imaging techniques which
      do not use ionizing radiations, but despite this common feature there remain many
      differences between them. Thus, color Doppler sonography is a cost-effective
      technique using mechanical waves and providing real-time images while magnetic
      resonance imaging is much more expensive, uses magnetic fields and radiofrequency
      energy and provides static images. The former method is very sensitive in
      detecting focal liver lesions > 1 cm, but its specificity in characterization is
      not as good, not even with the color Doppler technique. The main differences
      between color Doppler sonography, with and/or without echocontrast agents, and
      contrast-enhanced (Gadolinium chelates) dynamic magnetic resonance imaging in
      focal liver lesions can be summarized as follows: (1) magnetic resonance imaging
      depicts tumor vascularization only after paramagnetic contrast media injection.
      Enhanced images completely depend upon the contrast agent and cannot be achieved
      without it. In contrast, color Doppler signal is not modified by the contrast
      agent, it just becomes stronger. (2) Contrast-enhanced magnetic resonance signal
      (as well as contrast-enhanced computed tomography signal) provides more pieces of
      information than color Doppler signal about the flow characteristics of liver
      nodules--i.e. it shows not only blood flow (hyper-/hypovascular nodule), but also
      the interstitial spread of the agent and its wash-out. For example,
      hepatocellular carcinoma and focal nodular hyperplasia have similar perfusion
      while agent spread and wash-out decrease very quickly in the former and more
      slowly in the latter, except for the low decrease of the central scar. (3) Color
      Doppler technology improvements, higher sensitivity to slow flows and better
      signal/noise ratio reduce the applications of contrast-enhanced sonography in
      focal liver lesions because the agents modify only sensitivity and not the
      imaging in slow flow studies. (4) The higher cost of contrast studies is
      justified only in selected cases, namely treatment follow-up in the lesions with
      rich pretreatment vascularization. Finally, the higher cost of contrast magnetic
      resonance studies is justified to increase sensitivity and especially to allow
      lesion characterization.

PMID- 9652527
TI  - Image quality control in breast ultrasound.
AB  - Sonography is well suited for breast studies. Adequate equipment is needed to
      acquire high quality images because several technical factors influence
      ultrasound images. Thus, the use of high frequency dynamic scanning probes, the
      ultrasound beam focusing corrected for the near field, the adjustment of the gain
      and image contrast may all interfere with ultrasound beam reflection and
      scattering, determined by the heterogeneity of the gland parenchyma. In the last
      few years, a line of ultrasound equipment dedicated to this kind of application
      has been developed with 'small parts' transducers and frequencies ranging 10-13
      MHz. These units can improve the evaluation of superficial structures and provide
      diagnostic results that conventional equipment cannot achieve. The higher the
      quality, the more a sonographic image corresponds to real anatomy. This
      capability depends on the different kinds of system resolution. Axial spatial
      resolution is the capability to resolve discrete structures along the beam axis.
      Pulse length is inversely proportional to frequency and thus, the higher the
      transducer frequency, the better the axial resolution. However, the increase in
      frequency reduces the depth of penetration of the ultrasound beam. The spectrum
      of frequencies emitted by the crystal has been recently modified in order to
      obtain a good trade-off between the beam resolution and its penetration. Indeed,
      the development of the multifrequency technology allowed to improve the near
      field resolution while retaining a good penetration into the distant field.
      Furthermore, the use of compound ceramics with a broad bandwidth helps Doppler
      analysis because flow studies are optimized by low frequencies, whereas two
      dimensional morphologic imaging is optimized by high frequencies. Lateral spatial
      resolution is the capability to resolve discrete structures perpendicular or
      lateral to the beam axis. This parameter strictly depends on the size of the
      ultrasound beam section and it is optimal only in the focal area. Therefore, it
      improves with narrow beams. Several transducers are available in breast
      sonography, but the most adequate one is currently the annular transducer. The
      equipment should be able to detect even slight differences in acoustic impedance
      between the several breast tissues. This may be obtained by optimizing the
      dynamic range and the pre- and postprocessing setting. Apart from equipment, two
      other technical factors should be optimized to obtain high quality images, namely
      beam intensity and gain curve. A new Doppler technique has been recently
      introduced: power Doppler, which allows the demonstration of breast nodule
      vascularization with higher sensitivity than color Doppler. Finally, a rigorous
      examination technique is required to obtain high quality images. In the last few
      years, several quality assurance programs have been introduced. Dedicated
      phantoms are generally used. Recently, computer systems have been also developed.

PMID- 9652528
TI  - What's new in mammography.
AB  - Early diagnosis of breast cancer plays the leading role in reducing mortality
      rates and improving the patients' prognosis: mammography is the most sensitive
      technique currently available for the detection of nonpalpable lesions and
      therefore the method of choice. However, mammography has some limitations and the
      technique must be improved with technological devices without affecting image
      quality. This could be the target to increase diagnostic accuracy. Mammography
      sensitivity and specificity are now improved with the digital computer assisted
      technique, teleradiology, digital tomosynthesis or digital angiography--used to
      study microvascularization--3D imaging or synchrotron light, and laser
      mammography. Such other technological devices as Mammospot reduce breast
      thickness and provide better breast compression. Digital mammography can be
      carried out with film or direct digitization. The advantages of the digital
      technique are a shorter examination time, less storage space, electronic image
      recording, with image 'adjustments' made by the radiologist, and especially
      computerized analysis. The computer aided diagnosis can be defined as the
      diagnosis made by the radiologist who considers the results of computerized
      analysis as a 'second opinion'. In this way incidental mistakes made by
      radiologists, can be corrected by the computer analysis. Computers are a basic
      element also in teleradiology, which needs immediate and simultaneous admittance
      to the patient's history and permits radiology optimization in rural areas too.
      As for tomosynthesis, it permits to study a single slice of the breast without
      glandular tissue overlapping, which is useful in dense breasts where the
      diagnosis can be made with a lower X-ray dose. Moreover, this method fits the
      current mammographic systems easily. 3D imaging is still a work in progress.
      Synchrotron mammography is used only on surgery specimens, where it exhibits high
      resolution and contrast, depicting structures and details missed by conventional
      mammography. Breast DSA allows the study of vessels < 0.20 mm in diameter and of
      fine microvascular details; it can also demonstrate neoangiogenesis. Laser
      mammography permits bilateral examinations of the breast in 10-15 mins and is
      currently used also for breast cancer therapy, although only in animal trials. To
      conclude, after reviewing new techniques and evaluating the real cost/benefit
      ratio for each of them, conventional mammography remains the most sensitive tool
      for breast cancer diagnosis.

PMID- 9652530
TI  - MR state of the art.
AB  - Magnetic resonance imaging is undergoing continual and progressive evolution. To
      make a high quality examination, some requirements are mandatory, such as high
      spatial and contrast resolution to identify lesions and high temporal resolution
      to characterize them. We review the most important new magnetic resonance
      technologies, both those which are already available and used in clinical
      practice and those which are still to be developed. We analyze such technologic
      and methodolgic features as magnetic field strength, gradients, surface coils,
      echoplanar imaging, fat suppression techniques and magnetization transfer,
      contrast agents, automatic injectors, image postprocessing, computer assisted
      diagnosis, magnetic resonance-guided biopsy and spectroscopy. All these factors
      are in continuous evolution and new technologies anticipate, in the near future,
      faster examinations with very high spatial and contrast resolution, with magnetic
      resonance-guided cytologic and histologic aspiration biopsies, as well as
      spectroscopic studies of previously identified lesions. To perform a correct,
      state-of-the-art magnetic resonance examination of the breast, we need high
      strength gradients with high slew rate and bilateral coils. Finally, we discuss
      new technologies and methods which will increase the accuracy of magnetic
      resonance studies of the breast, improving image quality and decreasing execution
      time. Thus, magnetic resonance spectroscopy, allowing in vivo biochemical tissue
      analysis, seems to have high potentials; even though they are still difficult to
      define, the technique is sure to have major diagnostic impact also in monitoring
      the results to different treatments.

PMID- 9652529
TI  - Breast ultrasound and new technologies.
AB  - Technological advances are opening new fields of investigation for breast
      ultrasound. Specificity and color Doppler, staging and extended clinical roles in
      benign conditions are reviewed according to the state-of-the-art technology.
      Annular arrays are the best technical choice but new broadband linear arrays
      approach their quality and allow to visualize very slow flows within the breast.
      Still limitations exist and ultrasound is not suitable for screening. Providing
      better definition of normal as well as abnormal features, high-resolution
      sonography improves the specificity of the diagnosis for the majority of nodules
      and allows a better definition of both local and regional staging in nodular and
      diffuse conditions. Color Doppler and contrast media are increasing ultrasound
      specificity and are particularly useful in evaluating vascularity during
      therapies. Impressive results are achieved in the study of multifocal and
      multicentric carcinomas, in determining the degree of tumoral invasion of the
      surrounding tissues and of the ducts. Local and regional staging are greatly
      improved; the information given to the surgeon is more precise and allows easier
      therapeutic decisions. The diagnostic role of high-frequency ultrasound is also
      convincing in most benign conditions like inflammations, traumas and duct
      ectasia. In most of these conditions sonography is the best imaging modality to
      study the disease type and extent. The ability to monitor treatment efficacy or
      the natural outcome makes ultrasound and color Doppler a gold standard for breast
      inflammations.

PMID- 9652531
TI  - Color Doppler sonography.
AB  - The authors report the results obtained with color Doppler sonography in the
      study of breast conditions. Color Doppler allows to detect the following main
      features in breast conditions: the presence of blood flow, vessel arrangement,
      vascularization extent, the number of vascular poles. To investigate slow flows,
      it is better to use low PRF values (not above 1 KHz) and low filters, while
      amplification should be set immediately above the system's noise threshold; the
      size of color Doppler box should be adjusted as small as possible to maximize
      sensitivity and minimize flash artifacts. In May 1992 to September 1997, 252
      patients with solid breast masses were examined with mammography, B-mode, color
      Doppler and power Doppler sonography (only 57 cases). We identified
      histologically (176 cases) or cytologically (77 cases) 141 carcinomas and 112
      benign solid lesions. The diameter of the 141 carcinomas ranged 0.4-4 cm (mean
      1.7), while the diameter of benign lesions ranged 0.7-3 cm (mean 1.5). The
      malignancy pattern was characterized by hypervascularity (92.9%), irregular and
      abundant (54.2%) vascularization and more than one vascular pole. Benign lesions
      were avascular (43.4%) with poor and peripheral vascularity (90%) and mostly
      showed only one vascular pole. The avascular cancers (10 cases) were three
      mucoid, five in situ and two small (0.7 and 0.9 cm) invasive ductal carcinomas.
      The six benign lesions with irregular and abundant vascularization and more than
      one vascular pole were proved to be two proliferating and three juvenile
      fibroadenomas and one phylloid tumor. These results are encouraging and suggest
      that this technique can be a useful adjunct to mammography and sonography in the
      differential, diagnosis of breast nodules.

PMID- 9652532
TI  - Dynamic imaging: scintimammography.
AB  - Although mammography remains the technique of choice for the early detection of
      breast cancer, new emerging breast imaging techniques such as ultrasound,
      magnetic resonance and radionuclide scanning have been investigated and included
      in many diagnostic protocols. This overview discusses the current problems
      related to radionuclide breast imaging trying to define its role in the
      management of women with suspicious breast lesions at mammography. A number of
      tumor-imaging agents have been recently used for the differential diagnosis of
      malignant and benign lesions in radiographically dense breasts and breasts with
      architectural distortions from prior biopsy or surgery or following radiation
      therapy. 99mTc-MIBI is the most used tracer which has become the paradigm of this
      new class of compounds suitable for breast imaging. The current sensitivity and
      specificity rates for breast scintigraphy with 99mTc-MIBI depend on a number of
      factors including lesion size and site. Sensitivity and specificity rates and
      positive and negative predictive values of 92, 89, 81 and 96%, respectively, have
      been reported in a large series of patients with palpable breast lesions, which
      figures have been confirmed in many other series. On the contrary, lower
      sensitivity has been reported for nonpalpable breast abnormalities or for lesions
      smaller than 1 cm. This observation, confirmed by many authors, implies that a
      new nonpalpable lesion that is suspicious for malignancy at mammography needs a
      histologic diagnosis. We also report the results of our recent studies on
      functional imaging with 99mTc-MIBI of the multidrug resistance phenotype in
      breast cancer patients. These studies followed an observation that this tracer is
      a suitable transport substrate for the P-glycoprotein (P-gp) which is commonly
      associated with the development of a multidrug resistance phenotype. We examined
      30 patients with histologically confirmed breast carcinoma who had received no
      previous chemotherapy or preoperative local irradiation. We found a positive and
      significant correlation between the efflux rates of 99mTc-MIBI determined by in
      vivo kinetic analysis and the P-gp levels measured in vitro by quantitative
      autoradiography in the same tumors (r = 0.62; p < 0.001). More recently, we
      tested whether tumor clearance of 99mTc-MIBI can predict the response to
      neoadjuvant chemotherapy in patients with locally advanced breast cancer. Thirty
      nine patients with stage III disease underwent 99mTc-MIBI scanning before
      neoadjuvant chemotherapy and the time to half-clearance of the tracer was
      calculated. The patients then received epirubicin and underwent mastectomy after
      completing chemotherapy. This study showed that a rapid tumor clearance of 99mTc
      MIBI (< or = 204 min) can predict the lack of tumor response to neoadjuvant
      chemotherapy with drugs affected by multidrug resistance phenotype in advanced
      breast carcinoma patients. However, slower tracer clearance (> or = 204 min) did
      not guarantee an objective tumor response to chemotherapy in all patients, in
      agreement with the existence of several P-gp-independent mechanisms of drug
      resistance. We conclude that the preliminary study of this phenotype would allow
      to predict the response to (neo)adjuvant chemotherapy and select the appropriate
      treatment regimen for each patient. Finally, radionuclide breast scanning may be
      helpful in the differential diagnosis of malignant and benign breast lesions as a
      guide to subsequent chemotherapy.

PMID- 9652533
TI  - Dynamic MRI of the breast.
AB  - OBJECTIVE: To describe the rationale, the technical requirements and the
      examination technique of dynamic magnetic resonance studies of the breast and to
      assess the role of this method in the clinical diagnostic protocol. MATERIAL AND
      METHODS: We reviewed the relative literature and compared the results with our
      personal experience. RESULTS: The earliest reports on the possibility of
      differentiating carcinoma from benign tissue with magnetic resonance imaging came
      from Germany, where in 1986 Heywang and coworkers used T1-weighted spin-echo
      sequences before and after i.v. Gd-DTPA administration with an imaging time of
      approximately 5 mins and 5 mm slice thickness. With advances in magnetic
      resonance technology, Heywang Koebrunner adopted a static three-dimensional fast
      low-angle shot technique permitting < 3 mins' imaging time and providing high
      resolution with thin slices. This approach may detect even the carcinoma which
      occasionally does not enhance in the typical rapid, intense way. A review of 400
      biopsy-proved lesions showed that all carcinomas enhanced strongly, all but 5%
      rapidly and 85% focally. Over 70% of benign masses exhibited no major contrast
      uptake, although some benign tumors and proliferative dysplasias enhanced
      strongly. At present, Heywang-Koebrunner use rapid three-dimensional gradient
      echo sequences (TR/TE 14/7, FA 25 degrees; at 1.0 T) which have the advantages of
      three-dimensional imaging and permit dynamic studies (< 1 min/sequence). The same
      sequence is used at our institution. The dynamic technique is advocated by Kaiser
      who in 1989 reported preliminary sensistivity and specificity values over 95%.
      The time/signal intensity curves revealed the rapid and strong enhancement of
      malignancies, the gradual and strong enhancement of the only fibroadenoma
      studied, and the gradual and mild contrast uptake of benign dysplasia. In 1992,
      in nearly 1000 dynamic examinations, Kaiser and Reiser reported 98.3%
      sensitivity, 97.0% specificity, 82.1% predictive value and 97.2% accuracy. The
      combination of rapid acquisition with techniques that preserve high spatial
      resolution may improve specificity by allowing the study of lesion morphology as
      well as of enhancement patterns. A whole-breast imaging technique has been
      reported which permits acquisition times < 15 s by partial sampling of the
      central k-space region superimposed on high-resolution three-dimensional images.
      CONCLUSIONS: Dynamic magnetic resonance imaging of the breast is currently an
      important step of the clinical protocol of breast diseases, but there is no
      established study protocol yet.

PMID- 9652534
TI  - Computerization in breast imaging and diagnosis.
AB  - Computerization in breast imaging is very important for activity management and
      for the qualitative and quantitative control of the diagnoses. The connection
      through a personal computer network is necessary for the simultaneous input of
      more data. The activity in our center is completely managed by a specific
      software which controls and facilitates the input of all personal,
      administrative, history, instrumental and pathological data. The encoded case
      history permits quick and accurate data input and the relative information is
      easy to understand. Database information can be used to make periodical
      administrative and diagnostic reports and queries, to elaborate useful data for
      scientific reports and to manage didactic material. The growing use of computers
      will permit the exchange of data among breast imaging centers and also create
      important data banks for breast cancer studies.

PMID- 9652535
TI  - Scintimammography with 99mTc-MDP: experience of the National Cancer Institute of
      Naples.
AB  - The role of scintimammography with 99mTc-MDP was investigated in patients with
      mammographic or clinical evidence of breast lesions, suspicious for malignancy,
      in our Department at the National Cancer Institute of Naples. The end-point of
      the study was to assess the uselfulness of this test in diagnosing or ruling out
      breast cancer in more than 2000 women. Scintimammography results were compared
      with those of mammography and ultrasound and categorized according to
      histological findings. Overall sensitivity was 92%, specificity was 90%, and
      accuracy 91%. Sensitivity was affected by the lesions exceeding 12 mm and
      specificity by sclerotic and/or hyaline or myxoid fibroadenomas, which may be
      positive. The major advantages of scintimammography appeared in the study of
      calcifications without a mass and of the indirect mammographic signs of breast
      cancer, such as distortion and asymmetry. Scintimammography with 99mTc-MDP is a
      reliable, safe and highly cost-effective procedure to diagnose or to rule out
      breast cancer, after mammography and ultrasound have yielded questionable
      results.

PMID- 9652536
TI  - Aryepiglottic fold: normal topography and clinical implications.
AB  - The aryepiglottic folds extend between the arytenoid cartilage and the lateral
      margin of the epiglottis on each side and constitute the lateral borders of the
      laryngeal inlet. They are involved in physiologic closure mechanisms of the
      larynx and in pathologic conditions such as inspiratory stridor. Information on
      the normal topography of the aryepiglottic folds is poor and controversial.
      Therefore, this region was reinvestigated in serial whole-organ sections of 25
      plastinated normal adult human larynges. Dorsally, the right and the left
      aryepiglottic folds are separated by the interarytenoid notch and comprise the
      corniculate and cuneiform cartilages, as well as numerous groups of mucous
      glands. Ventrally, the aryepiglottic folds are adjacent to the peri-epiglottic
      adipose tissue. Both regions are clearly separated by several layers of
      transversely oriented collagenous fiber layers. The muscular constituent of the
      aryepiglottic folds is only poorly developed, and no muscle fibers insert at the
      epiglottis. A coherent quadrangular membrane representing a ligamentous
      "skeleton" of the aryepiglottic folds is absent. A conspicuous collagenous fiber
      layer is found only to strengthen the free dorsal margin of the fold. Both
      muscular and ligamentous components may render the aryepiglottic folds
      sufficiently tense as to resist inspiratory inward suction in normal cases.
      However, pliability must be preserved to guarantee adequate folding in
      approximation of the aryepiglottic folds during deglutition. Thereby, the
      posterior part of the laryngeal inlet is closed, whereas the anterior part is
      probably closed by independent inward bulging of the peri-epiglottic adipose
      tissue.

PMID- 9652537
TI  - Blood supply of the tensor fasciae latae muscle.
AB  - The tensor fasciae latae (TFL) muscle has been successfully harvested as a
      myocutaneous flap in reconstructive surgery. Reports on the vascular supply of
      this muscle, however, are incomplete or inconclusive. Therefore the arterial
      pattern was examined by dissection in 100 injected human cadaveric specimens. It
      was observed that whereas 67 muscles were supplied exclusively by a single vessel
      derived from the ascending branch of the lateral circumflex femoral (LCF) artery,
      13 were supplied by a secondary vessel derived from the same branch, while 20
      muscles were supplied by two vessels, the larger one arising as before and the
      smaller from the descending branch of the LCF. Our observations reveal that
      although the majority of TFL muscles are clinically Type I (one vascular pedicle)
      according to the classification of Mathes and Nahai (1981), 20% are actually Type
      II (major and minor vascular pedicles).

PMID- 9652538
TI  - Biometry of the muscular branches of the median nerve to the forearm.
AB  - The aim of this study was to determine the biometry of the muscular branches of
      the median nerve to the forearm in ten embalmed upper limbs. We measured the
      length of the forearm and the level of origin of each muscular branch of the
      median nerve to the forearm from the middle of a line between the medial and
      lateral epicondyles. The level of origin of each branch was then calculated as a
      percentage of the length of the forearm. Mean length of the forearm was 25 +/-
      2.36 cm (range: 22-29 cm). Although the levels of origin of the proximal and
      distal nerves to pronator teres, and of the nerves to palmaris longus, flexor
      carpi radialis and flexor digitorum superficialis, were quite variable
      (coefficient of variation: CV > 48.61%), the level of origin of the anterior
      interosseous nerve (CV = 31.24%) and its branches (nerves to flexor pollicis
      longus and flexor digitorum profundus, CV = 20.06%) was less variable. These
      results suggest that the anterior interosseous nerve of the forearm is probably
      the nerve to connect in muscular free transfers in order to restore flexion of
      the fingers after damage to the flexor tendons to the forearm. We observed Martin
      Gruber communications in six out of ten dissections.

PMID- 9652539
TI  - Approach to dissection of the anterior thoracic wall and the entrance to the
      thoracic cavity.
AB  - Dissection of the anterior chest wall typically precedes the opening of the
      thoracic cavity. The techniques for exposing and subsequently reflecting or
      removing the structures of the anterior chest wall have been well described.
      However, these approaches that involve the systematic dissection of the layers of
      tissue overlying the anterior thoracic wall prior to the removal of the anterior
      thoracic wall render the pectoral regions and axillas unfit for continued study.
      The authors offer an alternative dissection that allows continued access to the
      thoracic cavity while maintaining the integrity of the pectoral and axillary
      regions. This new technique may facilitate more efficient use and complete study
      of each specimen.

PMID- 9652540
TI  - Postmortem blood tests for HIV, HBV, and HCV in a body donation program.
AB  - A retrospective analysis of the results of blood tests conducted on body donors
      received by the Anatomical Gift Registry of the Medical College of Wisconsin
      (MCW) was performed. Over the 5-year period from April 1992 through March 1997 a
      total of 785 body donors were tested for Human Immunodeficiency Virus (HIV) and
      Hepatitis B and C Viruses (HBV and HCV). Eighteen of the 785 donors (2.3%) tested
      positive for one of these infectious agents. Two donors were positive for HIV,
      six were positive for HBV and ten were positive for HCV. The death certificates
      and files of those donors who tested positive were reviewed and the results are
      presented here. Blood testing prior to the use of the body donors is an effective
      and reasonable way of identifying the presence of these infectious agents, thus
      reducing the risk to those who work with cadavers. The cost for the testing at
      MCW is about $60 per donor.

PMID- 9652541
TI  - Survey of cadaveric donor application files: 1978-1993.
AB  - Information derived from application files of potential cadaveric donors to our
      body donation program from the period of 1978-1993 was entered into a customized
      database to assess the characteristics of people contributing to such a program.
      A total of 1,267 application files were reviewed and the following information
      analyzed: 1) year of application submission, 2) age, 3) sex, 4) race, 5) marital
      status, 6) education, 7) occupation, and 8) disposition of cremains (return or
      not to family). Overall the typical body donor applicant to our program was
      likely to be a white married female homemaker of about 70 years of age. She was a
      high school graduate and chose not to have her cremains returned to her family.
      The males closely follow the above mentioned characteristics (with the exception
      of occupation), but were outnumbered by females in nearly every category
      throughout the span of our analysis. An analysis of the application numbers over
      the 15 year period of our survey indicated a reduction in applications during the
      period of 1982-1984 and a linear increase of applicant numbers from 1989 to 1993.
      Finally, we observed a tendency for married couples to donate together with 32.1%
      of our married applicants showing this phenomenon.

PMID- 9652542
TI  - Regeneration in the central nervous system: pharmacological intervention,
      xenotransplantation, and stem cell transplantation.
AB  - The factors inhibiting regeneration in the central nervous system (CNS) have been
      elaborated, debated, and studied for the past 70 years. Recent work has pointed
      to the fine balance that exists between repair and regeneration following CNS
      injury. Growth factors have featured prominently in this debate. In attempts to
      tip the scales toward regeneration and functional reconnection to damaged
      neurons, pharmacological intervention has come to the fore. However, a perennial
      concern has been that much of regeneration may be aberrant, although there is now
      evidence to suggest that this fear may have been exaggerated. In searching for
      additional avenues for achieving therapeutic reconstruction of damaged neural
      pathways, transplantation studies occupy a prominent place in the literature.
      Various principles have become established, and these have proved relevant for
      all approaches utilizing grafts. Xenotransplantation and stem cell
      transplantation are approaches with exciting potential. Circuitry can be
      effectively restored by xenotransplantation, including early indications of
      integration of pig dopaminergic neurons in Parkinson's disease. The considerable
      possibilities offered by the differentiation of neural stem cells into progenitor
      cells and then into neurons and glia are explored.

PMID- 9652543
TI  - Bilateral supernumerary rectus muscles of the orbit.
AB  - A bilateral anomaly of the rectus muscles and a unilateral variation of the
      levator palpebrae muscle were found in the right and left orbits of an 84-year
      old man. The anomaly was in the form of a supernumerary rectus muscle lying on a
      sagittal orientation between the optic nerve and lateral rectus muscle (in the
      right orbit) and adjacent to the inferior rectus muscle (in the left orbit). In
      each orbit the anomalous muscle originated occipitally from the common tendinous
      ring and frontally-near the eyeball-joined the terminal part of the inferior
      rectus. On its superior margin the anomalous muscle had, in the right orbit, a
      broad (4 mm), and in the left orbit a slender (2 mm) muscular bridge to the
      superior rectus muscle. Because of their connection to the superior rectus and
      their innervation by N.III the accessory orbital muscles are not deemed to be
      vestiges of the retractor bulbi muscle which, with the exception of the primates,
      is a typical occurrence in vertebrates and is always innervated by N.VI. Our
      anomalous orbital muscle must be explained as a supernumerary rectus muscle. A
      further variation occurred in the right orbit: an isolated medial part or belly
      of the levator palpebrae muscle (the so-called M. gracillimus). In primates this
      variation is known as a remnant of the membrana nictitans (third eyelid of the
      amniotes). Ignorance of anomalies in the orbital muscles may lead to confusion
      and error in diagnostic identification and surgical exposure.

PMID- 9652544
TI  - Anatomical conundrum: unusual position of the aortic arch.
AB  - At autopsy on a 72-year-old woman, the aortic arch showed an unusual arrangement,
      passing behind the trachea and esophagus and descending on the left side. The
      heart was normal, and death was due to unrelated causes. The nature of this
      anomaly is considered in respect of embryological development.

PMID- 9652545
TI  - A clinical conundrum: unilateral decerebrate rigidity.
AB  - A case is described in which, following a motorcycle accident resulting in a
      closed head injury, a young woman was rendered unconscious. On examination she
      was found to have unilateral decerebrate rigidity. Further clinical and
      radiological examination revealed that there was no damage to the limbs,
      vertebral column, or spinal cord. Readers are expected to be able to make an
      anatomical diagnosis on the basis of the facts presented.

PMID- 9652546
TI  - Endocrine mechanisms underlying reproductive toxicity in the developing rat
      chronically exposed to dietary lead.
AB  - A dose-response study was conducted in a rat model to examine the effects of
      lifetime lead exposure on the development of the reproductive system and the
      endocrine mechanisms underlying these effects. Time-impregnated female Sprague
      Dawley rats (n = 10-15/group) were exposed to lead acetate in the drinking water
      at levels of 0.05%, 0. 15%, or 0.45% (w/v) initiated on gestational day 5. At
      birth, litters were culled to four male and four female pups. Exposure of dams to
      lead was continued until weaning, following which, the pups continued to be
      exposed to lead acetate in drinking water until sacrifice. One male and one
      female pup from each litter were sacrificed at age 21, 35, 55, and 85 d. A
      significant dose-responsive decrease in birth weight and crown-to-rump length was
      observed in all lead-exposed litters. However, no marked effects were observed on
      anogenital distance/crown-to-rump length ratios. Lead exposure resulted in a
      delay in sexual maturity as measured by prostate weight in male pups and time of
      vaginal opening in female pups, which increased with lead dose. These disruptions
      in reproductive physiology were accompanied by a significant decrease in neonatal
      sex steroid levels and suppression of the plasma concentrations of testosterone
      (male) and estradiol (female) during puberty. In male pups, this was accompanied
      by a significant decrease in plasma luteinizing hormone (LH), elevated pituitary
      LH content, and a decrease in plasma testosterone/LH ratios at the highest dose.
      In female pups, although no effects were observed on plasma LH concentration, a
      similar significant elevation in pituitary LH content was observed during early
      puberty. Postpuberty, plasma LH and sex steroid concentrations were unaffected at
      any dose in spite of continued lead exposure. No significant effects were
      observed on epididymal sperm count in male pups at 85 d of age. In female pups,
      estrus cycling was only significantly disrupted at the highest lead dose. These
      data suggest that the reproductive axis is particularly sensitive to lead during
      specific developmental periods, resulting in delayed sexual maturation produced
      by suppression by sex steroid biosynthesis. The mechanisms underlying this appear
      to involve lead actions on both LH release and gonadal function. At low,
      environmentally relevant blood lead concentrations, adaptation to the continuous
      presence of the metal ion occurs and surprisingly little effect is observed on
      adult reproductive endocrinology and physiology.

PMID- 9652547
TI  - Endocrine mechanisms underlying the growth effects of developmental lead exposure
      in the rat.
AB  - A dose-response study was conducted to examine the growth suppression associated
      with developmental lead exposure in a rat model and to determine the endocrine
      mechanisms underlying these effects. Ad libitum intake of lead acetate (0.05% to
      0.45% w/v) was initiated in time-impregnated female Sprague-Dawley rats (n = 10
      15/group) at gestational day 5. At birth, pups were culled to four male and four
      females per litter. Lead exposure of dams continued until weaning, following
      which lead exposure of pups was continued until sacrifice at age 2 , 35, 55, and
      85 days. Birth weight and prepubertal and pubertal growth rates were
      significantly suppressed. Growth rates were suppressed to a much greater degree
      in male as compared to female pups. Decreased growth rates were accompanied by a
      significant decrease in plasma insulin-like growth factor 1 (IGF1) concentrations
      and (1) a significant increase in pituitary growth hormone (GH) content during
      puberty in pups of both sexes, (2) a delay in the developmental profiles of the
      GH-dependent male-specific liver enzymes cytochrome P-450 CYP2C11 and N-hydroxy-2
      acetylaminofluorene sulfotransferase, and (3) continued suppression of these
      enzymes in lead-exposed adult male pups. In addition, significant decreases in
      plasma sex steroids, testosterone (male) and 17beta-estradiol (female), were
      observed during puberty. Postpuberty, at age 85 d, both IGF1 and sex steroid
      levels were indistinguishable from control pups despite continued lead exposure.
      Growth rates were also similar in control and lead-exposed pups between age 57
      and 85 d. Data suggest that the mechanism underlying lead-induced sex-independent
      suppression of growth observed in these studies involves disruption of GH
      secretion during puberty. It is possible that the mechanisms underlying the
      greater suppression of somatic growth observed at puberty in lead-exposed male
      offspring may be due to the additional hypoandrogenization produced by the action
      of lead on the hypothalamic-pituitary-testicular axis.

PMID- 9652548
TI  - Disposition of 2-methylimidazole in rats.
AB  - 2-Methylimidazole (2-MI), widely used as a chemical intermediate, is also present
      in cigarette smoke and may form in food and forage as a result of ammoniation of
      simple sugars. 2-MI has been shown to be neurotoxic in several animal species and
      to alter serum levels of T3, T4, and thyroid-stimulating hormone (TSH) in the
      rat, apparently leading to hyperplasia of thyroid follicular cells. In order to
      better characterize 2-MI-induced toxicity, the disposition of [2-(14)C]-2-MI has
      been investigated following p.o. administration of either 5, 50, or 150 mg/kg to
      male F344 rats. Excretion data indicated that absorption of 2-MI was both rapid
      and proportional to dose in the range studied. Approximately 90% of the total
      dose was eliminated in urine within 24 h. Most of the remaining 14C was excreted
      in feces and as expired 14CO2. Excretion data were similar following i.v.
      administration of 5 mg/kg. Little or no enterohepatic circulation of compound
      occurred, since biliary excretion of 2-MI-derived 14C was negligible.
      Approximately 70% of the 14C excreted in urine, following all dosing, consisted
      of parent compound. High-performance liquid chromatography (HPLC) chromatograms
      for all treatment groups were similar, indicating that metabolism of 2-MI in rats
      was not affected by dose or route of administration.

PMID- 9652549
TI  - 1,1,2,2-Tetrachloroethane-induced early decrease of dolichol levels in rat liver
      microsomes and Golgi apparatus.
AB  - Dolichols are long-chain polyprenols containing 14-22 isoprene units, present in
      mammalian tissues as free dolichol (Free-Dol), fatty acyl dolichyl esters (Dol
      FA), and dolichyl phosphate (Dol-P). The hepatic level of Dol-P seems to be a
      rate-limiting factor for glycosylation processes. Previous studies from our
      laboratory demonstrated the susceptibility of the dolichol molecule to undergo
      radical attacks. Since the toxicity of 1,1,2,2-tetrachloroethane (TTCE)is
      dependent on the free-radical production during hepatic biotrasformation, it was
      of interest to determine whether this haloalkane might affect glycosylation
      mechanisms by changing dolichol levels and distribution in rat liver microsomes
      and Golgi apparatus (GA). Male Sprague-Dawley rats received a single dose of TTCE
      (574 mg/kg body weight) and were then sacrificed at different times (5, 15, 30,
      or 60 min). In the TTCE-treated rats both serum aspartate aminotransferase (AST)
      and alanine aminotransferase (ALT) activities and hepatic triglycerides (TG) were
      significantly higher than control, while microsomal glucose 6-phosphatase
      (G6Pase) activity was decreased. In total microsomes Dol-P levels considered rate
      limiting for the biosynthesis of the N-glycosylated proteins were significantly
      lower than in the control group 15 min after TTCE treatment. In normal rat liver,
      F1 secretory fraction of CA is 60-fold enriched in total dolichol content with
      respect to microsomes. In this compartment the total dolichol content, essential
      for the increase in membrane fluidity and permeability required for glycoprotein
      maturation and secretion, decreased significantly 5 min after TTCE treatment. Our
      results suggest that TTCE may affect dolichol functions in rat liver.

PMID- 9652550
TI  - Estimation of absorption of environmental contaminants in low-level exposure by
      pharmacokinetic analysis.
AB  - Inhalation pharmacokinetics of the environmental contaminants 1,1,1
      trichloroethane, tetrachloroethylene, trichloroethylene, benzene, and p
      dichlorobenzene were determined in male Sprague-Dawley rats, and data generated
      were used to obtain fundamental data for risk assessment of chronic low-level
      exposures to these substances. Measured amounts of the substances were injected
      into a closed chamber system in which a rat had been placed, and the
      concentration changes in the chamber air were examined. The pharmacokinetics of
      the substances were evaluated using linear or nonlinear compartment models. The
      metabolic elimination amounts at various exposure concentrations were
      extrapolated using the estimated pharmacokinetic parameters. At low (1 ppb)
      concentration exposure to benzene or trichloroethylene the fraction of
      elimination of these substances was 1.6 and 1.5 times higher, respectively, than
      that seen at high (10 ppm) concentration exposure. Extrapolation kinetics of low
      exposure data showed more trichloroethylene (0.0016 micromol/h/kg), benzene
      (0.0014 micromol/h/kg), and p-dichlorobenzene (0.00052 micromol/h/kg) was
      absorbed by the rats than 1,1,1-trichloroethane (0.000019 micromol/h/kg) and
      tetrachloroethylene (0.000029 micromol/h/kg). Although the exposure
      concentrations for all chemicals were equal, the differences in absorption
      quantities need to be considered in evaluation of potential risk assessment.

PMID- 9652551
TI  - Cadmium suppresses apoptosis induced by chromium.
AB  - Cadmium and chromium are both well-known human carcinogens, and common exposures
      to these metals are not infrequent. Recent studies have shown that hexavalent
      chromium induces apoptosis in Chinese hamster ovary (CHO) cells, suggesting an
      association of apoptosis with carcinogenesis. In contrast, induction of apoptosis
      by cadmium has been inconsistently observed. The present study was designed to
      determine if cadmium could induce apoptosis in CHO cells and if common exposure
      to cadmium and chromium would modify any apoptotic response. Apoptosis was
      evaluated by both agarose gel and in situ end-labeling methods. Apoptosis was
      observed at 48 h after treatment with 300 microM chromium (Na2CrO4) for 2 h.
      Cadmium alone at concentrations of 1, 5, or 10 microM (as CdCl2) did not induce
      apoptosis in these cells even at times up to 72 h after treatment. However, when
      CHO cells were concurrently exposed to cadmium and chromium, chromium-induced
      apoptosis was markedly suppressed in a cadmium concentration-related fashion.
      Cadmium did not consistently modify the cytotoxic effects of chromium, and
      significant increases in metallothionein were not induced by these metal
      treatments. These findings indicate that cadmium can block chromium-induced
      apoptosis. The suppression of apoptosis by cadmium may be a significant aspect of
      its carcinogenic mechanism.

PMID- 9652552
TI  - Working for safe and healthy work.

PMID- 9652553
TI  - Does IGF-I therapy in insulin-dependent diabetes mellitus limit complications?

PMID- 9652554
TI  - Platelet glycoprotein IIIa polymorphism and coronary thrombosis.

PMID- 9652555
TI  - Odour perception in chronic renal disease.

PMID- 9652556
TI  - Antibiotic prophylaxis after tick bites.

PMID- 9652557
TI  - It's my book.

PMID- 9652558
TI  - Vaccines 1997.

PMID- 9652559
TI  - Randomised trial of basiliximab versus placebo for control of acute cellular
      rejection in renal allograft recipients. CHIB 201 International Study Group.
AB  - BACKGROUND: Currently available immunosuppressive regimens for cadaver-kidney
      recipients are far from ideal because acute-rejection episodes occur in about 30%
      to 50% of these patients. In the phase III study described here we assessed the
      ability of basiliximab, a chimeric interleukin (IL)-2 receptor monoclonal
      antibody, to prevent acute-rejection episodes in renal allograft recipients.
      METHODS: 380 adult recipients of a primary cadaveric kidney transplant were
      randomly allocated, in this double-blind trial, to receive a 20 mg infusion of
      basiliximab on day 0 (day of surgery) and on day 4, to provide IL-2-receptor
      suppression for 4-6 weeks (n=193), or to receive placebo (n=187). Both groups
      received baseline dual immunosuppressive therapy with cyclosporin and steroids
      throughout the study. The primary outcome measure was incidence of acute
      rejection episodes during the 6 months after transplantation. Safety and
      tolerability were monitored over the 12 months of the study. FINDINGS: 376
      patients were eligible for intention-to-treat analysis (basiliximab, n=190;
      placebo, n=186). No significant differences in patient characteristics were
      apparent. The incidence of biopsy-confirmed acute rejection 6 months after
      transplantation was 51 (29.8%) of 171 in the basiliximab group compared with 73
      (44.0%) of 166 in the placebo group (32% reduction; 14.2% difference [95% Kaplan
      Meier CIs 3% to 24%], p=0.012). The incidence of steroid-resistant first
      rejection episodes that required antibody therapy was significantly lower in the
      basiliximab group (10% vs 23.1%, 13.1% difference [5.4% to 20.8%], p<0.001). At
      weeks 2 and 4 post-transplantation, the mean daily dose of steroids was
      significantly higher in the placebo group (p<0.001 with one-way analysis of
      variance). The incidence of graft loss at 12 months post-transplantation was 23
      (12.1%) of 190 in the basiliximab group and 25 (13.4%) of 186 in the placebo
      group (1.3% difference [-5% to 9%], p=0.591). The incidence of infection and
      other adverse events was similar in the two treatment groups. The acute
      tolerability of basiliximab was excellent, with no evidence of cytokine-release
      syndrome. 14 deaths (basiliximab n=9; placebo n=5; -2.0% difference [-6% to 2%],
      p=0.293) occurred during the 12-month study and a further three deaths
      (basiliximab n=1; placebo n=2) occurred within the 380-day cut-off period. One
      post-transplantation lymphoproliferative disorder was recorded in each group.
      INTERPRETATION: Prophylaxis with 40 mg basiliximab reduces the incidence of acute
      rejection episodes significantly, with no clinically relevant safety or
      tolerability concerns.

PMID- 9652560
TI  - Randomised placebo-controlled trial of human recombinant insulin-like growth
      factor I plus intensive insulin therapy in adolescents with insulin-dependent
      diabetes mellitus.
AB  - BACKGROUND: Good glycaemic control in insulin-dependent diabetes mellitus (IDDM)
      to prevent complications may be difficult to achieve during adolescence, because
      abnormalities in production of growth hormone or insulin-like growth-factor-I
      (IGF-I) can lead to lower insulin sensitivity. Recombinant human IGF-I (rhIGF-I)
      given as an adjunct to insulin therapy in IDDM, might improve glycaemic control
      in adolescents; we investigated the effects of the addition of IGF-I in a
      randomised, double-blind, placebo-controlled trial. METHODS: 53 patients with
      IDDM (26 male, 27 female) with a median age of 16.1 years (range 10.8-20.6) and
      diabetes of more than 2 years' duration were randomly assigned subcutaneous rhIGF
      I (20 or 40 microg/kg daily [n=18, n=18, respectively]) or placebo (n=17), both
      in addition to multiple-injection insulin therapy for 24 weeks. The primary
      endpoint, glycated haemoglobin (HbA1c) and routine biochemistry were measured
      every 4 weeks. Retinal photographs and glomerular-filtration rates were assessed
      at base line and at the end of the study. Data were analysed by intention to
      treat. FINDINGS: With a dose of 40 microg/kg rhIGF-I daily, we found significant
      reductions in HbA1c compared with placebo (p=0.03), without changes in body-mass
      index, rate of hypoglycaemia, insulin dose, or circulating concentrations of IGF
      binding proteins 1 and 3. The greatest median change in HbA1c of -0.6% (range 
      2.8 to -1.5%) was seen with rhIGF-I 40 microg/kg at week 12, but was not
      sustained at week 24. The greatest reductions in HbA1c at week 24 were seen among
      patients with the greatest changes in IGF-I concentrations (r=-0442, p=0.002).
      Retinal photographs, renal function (glomerular filtration rate and urinary
      albumin excretion), and routine biochemistry showed no adverse events.
      INTERPRETATION: Our data confirm that rhIGF-I as an adjunct to insulin therapy
      can improve HbA1c values in adolescents with IDDM without overt toxic effects,
      but they raise questions about whether these effects can be sustained in cases of
      poor compliance or reduced bioefficacy.

PMID- 9652561
TI  - Randomised placebo-controlled trial of rhesus-human reassortant rotavirus vaccine
      for prevention of severe rotavirus gastroenteritis.
AB  - BACKGROUND: Rotavirus is the most common cause of acute childhood
      gastroenteritis. Vaccination with live oral heterologous rotavirus vaccines may
      prevent rotavirus gastroenteritis. We assessed the efficacy of rhesus-human
      reassortant rotavirus tetravalent vaccine (RRV-TV) against severe rotavirus
      gastroenteritis in Finnish children in a randomised placebo-controlled double
      blind trial. METHODS: Placebo or RRV-TV (titre 4x10(5) plaque-forming units) was
      given to infants at ages 2, 3, and 5 months. The children were followed up for
      one or two rotavirus epidemic seasons. The main outcome measure was protection
      against severe rotavirus gastroenteritis (score > or =11 on a 20-point severity
      scale). 2398 children were enrolled and received at least one dose of RRV-TV
      (n=1191) or placebo (n=1207). The primary efficacy analysis was based on children
      who received three doses of RRV-TV (n=1128) or placebo (n=1145). FINDINGS: 256
      episodes of rotavirus gastroenteritis occurred at any time during the study; 65
      were among 1191 RRV-TV recipients, and 191 among 1207 placebo recipients (vaccine
      efficacy 66% [95% CI 55-74]; intention-to-treat analysis). 226 episodes were
      included in the primary efficacy analysis of fully vaccinated children (54 among
      1128 RRV-TV recipients, 172 among 1145 placebo recipients; vaccine efficacy 68%
      [57-76]). 100 episodes were severe, eight in RRV-TV recipients and 92 in placebo
      recipients (vaccine efficacy 91% [82-96]). INTERPRETATION: RRV-TV vaccine was
      highly effective against severe rotavirus gastroenteritis in young children.
      Incorporation of this vaccine into routine immunisation schedules of infants
      could reduce severe rotavirus gastroenteritis by 90% and severe gastroenteritis
      of all causes in young children by 60%.

PMID- 9652562
TI  - Long-term follow-up of patients from a randomised trial of atrial versus
      ventricular pacing for sick-sinus syndrome.
AB  - BACKGROUND: In a previous study of 225 patients with sick-sinus syndrome
      randomised to either single-chamber atrial pacing (n=110) or single-chamber
      ventricular pacing (n=115), we found that after a mean follow-up of 3.3 years,
      atrial pacing was associated with significantly less atrial fibrillation and
      thromboembolism whereas there was no significant difference in mortality and
      heart failure between the two groups. We aimed to find out whether this
      beneficial effect of atrial pacing is maintained during extended follow-up of up
      to 8 years. METHODS: Follow-up visits for all patients were at 3 months, 12
      months, then once a year at which patients had a physical examination, ECG
      recording, and pacemaker check-up. Endpoints were mortality, cardiovascular
      death, atrial fibrillation, thromboembolic events, heart failure, and
      atrioventricular block. Data was analysed on Dec 31, 1996. FINDINGS: At long-term
      follow-up, 39 patients from the atrial group had died versus 57 from the
      ventricular group (relative risk 0.66 [95% CI 0.44-0.99]; p=0.045). 19 patients
      from the atrial group and 39 patients from the ventricular group died from a
      cardiovascular cause (0.47 [0.27-0.82]; p=0.0065). The cumulative incidences of
      atrial fibrillation and chronic atrial fibrillation were also significantly lower
      in the atrial group than in the ventricular group (0.54 [0.33-0.89], p=0.012 and
      0.35 [0.16-0.76], p=0.004, respectively). Thromboembolic events occurred in 13
      patients in the atrial group and 26 in the ventricular group (0.47 [0.24-0.92],
      p=0.023). Heart failure was less severe in the atrial group than in the
      ventricular group (p<0.05). In multivariate analysis, atrial pacing was
      significantly associated with freedom from thromboembolic events (0.47 [0.24
      0.92], p=0.028) and survival from cardiovascular death (0.52 [0.30-0.91],
      p=0.022), but no longer with overall survival (0.71 [0.46-1.08], p=0.11) or
      chronic atrial fibrillation (0.45 [0.20-1.05], p=0.063). Atrioventricular block
      occurred in four patients in the atrial group (0.6% annual risk). INTERPRETATION:
      The beneficial effect of atrial pacing found in our previous study is enhanced
      substantially over time. Patients with sick-sinus syndrome should be treated with
      an atrial rather than ventricular-pacing system because after long-term follow
      up, atrial pacing is associated with a significantly higher survival, less atrial
      fibrillation, fewer thromboembolic complications, less heart failure, and a low
      risk of atrioventricular block.

PMID- 9652564
TI  - Loss of control after a cup of coffee.

PMID- 9652563
TI  - Platelet glycoprotein IIIa polymorphisms and risk of coronary stent thrombosis.
AB  - BACKGROUND: Coronary stents are an effective treatment for selected coronary
      stenoses. However, thrombosis of the stented segment is a major adverse
      complication. Platelet aggregation has a key role in stent thrombosis. We
      investigated whether a polymorphism of platelet glycoprotein IIIa gene (PIA2) is
      associated with an increased risk of coronary stent thrombosis. METHODS: 318
      consecutive patients were followed up for 30 days after coronary stent insertion.
      The primary endpoints were death, myocardial infarction, stent-vessel occlusion,
      and coronary artery bypass surgery. Gel electrophoresis of PCR products was used
      to identify the PIA1 and PIA2 alleles. The relative risk of stent occlusion was
      calculated from the odds ratio on logistic regression analysis. FINDINGS: 63
      (19.8%) of patients had the PIA2 allele and 255 (80.2%) were homozygous for PIA1.
      Baseline clinical, angiographic, and procedural features did not differ between
      the groups with and without the PIA2 allele. Occlusion of the stent vessel
      occurred in five (1.9%) patients homozygous for PIA1 and six (9.5%) patients with
      PIA2 allele (odds ratio 5.26 [95% CI 1.55-17.85]). On multivariate regression
      analysis PIA1/A2 genotype was the only significant independent predictor of stent
      thrombosis. INTERPRETATION: Patients with the pIA2 allele have an increased risk
      of coronary stent thrombosis, which may warrant antiplatelet therapy with
      glycoprotein-IIb/IIIa inhibitors, although bleeding complications may also
      increase.

PMID- 9652565
TI  - Magnetic resonance neurography of peripheral nerve degeneration and regeneration.

PMID- 9652567
TI  - Mutations in the MEN I gene in sporadic neuroendocrine tumours of
      gastroenteropancreatic system.

PMID- 9652568
TI  - Pseudolymphoma at site of clonidine patch.

PMID- 9652566
TI  - Simvastatin reduces monocyte-tissue-factor expression type IIa
      hypercholesterolaemia.

PMID- 9652569
TI  - Bilateral dorsolateral subthalamotomy for advanced Parkinson's disease.

PMID- 9652570
TI  - Previous cytomegalovirus or Chlamydia pneumoniae infection and risk of restenosis
      after percutaneous transluminal coronary angioplasty.

PMID- 9652571
TI  - Monitoring compliance with antituberculous treatment by detection of isoniazid in
      urine.

PMID- 9652572
TI  - Microscopic haematuria: a diagnostic aid in giant-cell arteritis?

PMID- 9652573
TI  - UK report calls for additional smear test re-reads.

PMID- 9652576
TI  - Human rights give way to civil rights in Argentina.

PMID- 9652575
TI  - M cells: portals to the mucosal immune system.

PMID- 9652578
TI  - World Bank's policy of structural adjustment under fire in India.

PMID- 9652577
TI  - Ireland rules out compulsory HIV testing.

PMID- 9652579
TI  - Struggle worldwide to regain consumers' faith in food.

PMID- 9652580
TI  - Portal hypertension and variceal haemorrhage.

PMID- 9652581
TI  - Applications of molecular microbiology to vaccinology.
AB  - Genetics, cell biology, and whole-genome sequencing of pathogens have changed
      dramatically the opportunities to investigate the epidemiology, pathogenesis,
      diagnosis, and control of microbial diseases. For example, recombinant DNA and
      PCR are powerful tools used to isolate genes whose role in pathogenicity can be
      investigated in biologically relevant virulence assays. Vaccines that target one
      or more of these genes can then be developed. Complete genome sequences of
      microbes provide an inventory of the genes encoding every virulence factor and
      potential immunogen. Candidate vaccines can be selected and developed using
      various approaches, including the recent innovation of immunisation with nucleic
      acids. Although many successful vaccines have been and will continue to be
      developed through empirical approaches, molecular microbiology provides a
      rational basis for discovery, development, and implementation of safer, more
      effective and, potentially cheaper vaccines.

PMID- 9652582
TI  - Osler and Ernulf's curse.

PMID- 9652583
TI  - The truth about Israeli medical ethics.

PMID- 9652584
TI  - Stress and long-term coronary risk.

PMID- 9652585
TI  - Liver abnormalities and hydrochlorofluorocarbons.

PMID- 9652586
TI  - Liver abnormalities and hydrochlorofluorocarbons.

PMID- 9652587
TI  - Paraneoplastic limbic encephalitis.

PMID- 9652588
TI  - Paraneoplastic limbic encephalitis.

PMID- 9652589
TI  - HIV-1 infection associated with abnormal vaginal flora morphology and bacterial
      vaginosis.

PMID- 9652590
TI  - HIV-1 infection associated with abnormal vaginal flora morphology and bacterial
      vaginosis.

PMID- 9652591
TI  - Childhood idiopathic thrombocytopenic purpura.

PMID- 9652592
TI  - Childhood idiopathic thrombocytopenic purpura.

PMID- 9652593
TI  - Chorionic villus sampling versus early amniocentesis.

PMID- 9652594
TI  - Chorionic villus sampling versus early amniocentesis.

PMID- 9652595
TI  - GTP-cyclohydrolase and vitiligo.

PMID- 9652597
TI  - East-West mortality gap and environment.

PMID- 9652596
TI  - Left-ventricular dysfunction in diabetic patients with leucine tRNA mutation.

PMID- 9652598
TI  - Population growth in Africa.

PMID- 9652599
TI  - Authorship of complex investigations.

PMID- 9652600
TI  - Risk factor epidemiology.

PMID- 9652601
TI  - A thirst for progress in patients' care.

PMID- 9652602
TI  - Loaded, but no place to go.

PMID- 9652603
TI  - More clinical judgment, fewer "clinical" judges.

PMID- 9652604
TI  - Prognosis of BRCA1 hereditary breast cancer.

PMID- 9652605
TI  - Insulin-sensitising agents in polycystic-ovary syndrome.

PMID- 9652606
TI  - Screening for urinary abnormalities: worth doing and worth doing well.

PMID- 9652607
TI  - Not all is dead in HIV-1 graveyard.

PMID- 9652608
TI  - Measuring height: to stretch or not to stretch?

PMID- 9652609
TI  - Number-needed-to-treat and placebo-controlled trials.

PMID- 9652610
TI  - Recurrence risks in offspring of adults with major heart defects: results from
      first cohort of British collaborative study.
AB  - BACKGROUND: Congenital heart defects are generally assumed to have a
      multifactorial aetiology. We have tested this hypothesis by studying adults with
      heart defects and their families. METHODS: We identified 1094 patients who
      survived surgery for major cardiac defects before 1970. We chose individuals with
      disturbance of situs or segmental connection, with atrioventricular septal defect
      or with tetralogy of Fallot. After exclusion and non-participation, 727
      individuals were traced. Each was visited by an investigator and completed a
      detailed questionnaire. If possible, all "normal" offspring were examined by a
      paediatric cardiologist. FINDINGS: The 727 individuals had 393 live offspring.
      There were 71 miscarriages and five terminated pregnancies. Overall, we found
      recurrent heart defects in 16 liveborn offspring--a recurrence risk of 4.1%. This
      result differed significantly from sibling risk (2.1%; p=0.021). More congenital
      heart defects occurred in the offspring of affected women than in those of
      affected men (p=0.047); when all malformations (cardiac and non-cardiac) in the
      offspring were taken into account the excess was more significant (p=0.032). We
      found an excess of miscarriages in the offspring of affected women (p=0.001). In
      tetralogy of Fallot, heart defects occurred in seven (3.1%) of 223 offspring, 12
      (2.2%) of 539 siblings, five (0.3%) of 1575 second-degree relatives, and eight
      (0.3%) of 2728 third-degree relatives. INTERPRETATION: Our findings do not
      support a polygenic basis for all heart defects. Atrioventricular septal defect
      seems to be a single-gene defect and tetralogy of Fallot a polygenic disorder
      with a small number of interacting genes. Our data suggest that isolated
      transposition of the great arteries is a sporadic defect.

PMID- 9652611
TI  - Survival and tumour characteristics of breast-cancer patients with germline
      mutations of BRCA1.
AB  - BACKGROUND: Hereditary breast cancer has been associated with mutations in the
      BRCA1 and BRCA2 genes and has a natural history different from sporadic breast
      cancer. We investigated disease-free and overall survival for patients with a
      proven BRCA1 alteration. METHODS: We estimated disease-free and overall survival
      for 49 Dutch patients from 19 consecutive families with a proven specific BRCA1
      mutation and one family with strong evidence for linkage to the BRCA1 gene. We
      compared clinical outcome and data on tumour size, histology, axillary nodal
      status, contralateral breast cancer, and oestrogen-receptor and progesterone
      receptor status with those of 196 patients with sporadic breast cancer, matched
      for age and year of diagnosis. FINDINGS: Disease-free survival for BRCA1 and
      sporadic patients at 5 years was 49% (95% CI 33-64) and 51% (43-59), respectively
      (p=0.98). Overall survival at 5 years was 63% (47-76) and 69% (62-76),
      respectively (p=0.88). Recurrence and death rates did not differ significantly
      between groups. Hazard ratios for recurrence and death among BRCA1 patients were
      1.00 (0.65-1.55) and 1.04 (0.63-1.71) relative to sporadic patients (p=0.88), and
      these did not differ significantly after adjustment for prognostic factors.
      Patients with BRCA1-associated breast cancer had twice as many progesterone
      receptor-negative tumours (p<0.005) and development of contralateral breast
      cancer was four to five times as frequent as in the sporadic group (p<0.001).
      INTERPRETATION: We showed that disease-free and overall survival were similar for
      sporadic and hereditary breast cancer in the presence of different tumour
      characteristics, which has implications for screening prophylactic therapy, and
      different treatments of hereditary breast cancer.

PMID- 9652612
TI  - Randomised trial of laparoscopic versus open cholecystectomy for acute and
      gangrenous cholecystitis.
AB  - BACKGROUND: Laparoscopic cholecystectomy (LC) has become the treatment of choice
      for elective cholecystectomy, but controversy persists over use of this approach
      in the treatment of acute cholecystitis. We undertook a randomised comparison of
      the safety and outcome of LC and open cholecystectomy (OC) in patients with acute
      cholecystitis. METHODS: 63 of 68 consecutive patients who met criteria for acute
      cholecystitis were randomly assigned OC (31 patients) or LC (32 patients). The
      primary endpoints were hospital mortality and morbidity, length of hospital stay,
      and length of sick leave from work. Analysis was by intention to treat. Suspected
      bile-duct stones were investigated by preoperative endoscopic retrograde
      cholangiography (LC group) or intraoperative cholangiography (OC group).
      FINDINGS: The two randomised groups were similar in demographic, physical, and
      clinical characteristics. 48% of the patients in the OC group and 59% in the LC
      group were older than 60 years. 13 patients in each group had gangrene or
      empyema, and one in each group had perforation of the gallbladder causing diffuse
      peritonitis. Five (16%) patients in the LC group required conversion to OC, in
      most because severe inflammation distorted the anatomy of Calot's triangle. There
      were no deaths or bile-duct lesions in either group, but the postoperative
      complication rate was significantly (p=0.0048) higher in the OC than in the LC
      group: seven (23%) patients had major and six (19%) minor complications after OC,
      whereas only one (3%) minor complication occurred after LC. The postoperative
      hospital stay was significantly shorter in the LC than the OC group (median 4
      [IQR 2-5] vs 6 [5-8] days; p=0.0063). Mean length of sick leave was shorter in
      the LC group (13.9 vs 30.1 days; 95% CI for difference 10.9-21.7).
      INTERPRETATION: Even though LC for acute and gangrenous cholecystitis is
      technically demanding, in experienced hands it is safe and effective. It does not
      increase the mortality rate, and the morbidity rate seems to be even lower than
      that in OC. However, a moderately high conversion rate must be accepted.

PMID- 9652613
TI  - Randomised placebo-controlled crossover trial on effect of inactivated influenza
      vaccine on pulmonary function in asthma.
AB  - BACKGROUND: Despite current recommendations, many people with asthma do not
      receive annual vaccination against influenza, partly because of concern that
      vaccine may trigger exacerbations. Colds can trigger exacerbations, which may be
      mistaken for vaccine-related adverse events. We undertook a double-blind placebo
      controlled multicentre crossover study to assess the safety of influenza vaccine
      in patients with asthma, with allowance for the occurrence of colds. METHODS: We
      studied 262 patients, aged 18-75 years, who recorded daily peak expiratory flow
      (PEF), respiratory symptoms, medication, medical consultations, and hospital
      admissions for 2 weeks before the first injection and until 2 weeks after the
      second injection. Order of injection (vaccine and placebo) was assigned randomly.
      There was an interval of 2 weeks between injections. The main outcome measure was
      an exacerbation of asthma within 72 h of injection (defined as a fall in PEF of
      >20%). FINDINGS: Among 255 participants with paired data, 11 recorded a fall in
      PEF of more than 20% after vaccine compared with three after placebo (McNemar's
      test p=0.06); a fall of more than 30% was recorded by eight after vaccine
      compared with none after placebo (binomial test p=0.008). However, when
      participants with colds were excluded, there was no significant difference in the
      numbers with falls of more than 20% between vaccine and placebo (six vs three;
      binomial test p=0.51), although the difference for PEF decreases of more than 30%
      approached significance (five vs none; binomial test, p=0.06). This association
      was confined to first-time vaccinees. INTERPRETATION: Our findings indicate that
      pulmonary-function abnormalities may occur as a complication of influenza
      vaccination. However, the risk of pulmonary complications is very small and
      outweighed by the benefits of vaccination.

PMID- 9652614
TI  - Lung as reservoir for antidepressants in pharmacokinetic drug interactions.
AB  - BACKGROUND: Although high-affinity imipramine binding sites have been reported in
      both rat and human lung, the role of the lungs in the pharmacokinetics of
      antidepressants has not received much attention. Substantial accumulation of
      selective serotonin-reuptake inhibitors (SSRIs) in the lungs has been reported.
      We have investigated the role of the lungs in pharmacokinetic drug interactions
      between tricyclic antidepressants and SSRIs. METHODS: We used a carbon-11
      labelled form of the imipramine derivative cyanoimipramine to measure uptake in
      the lungs and brain of healthy volunteers by positron emission tomography.
      Clomipramine (50 mg) was administered to measure the effect of antidepressants
      with high affinity for the serotonin transporter on lung and brain uptake.
      FINDINGS: A large proportion of the injected 11C-cyanoimipramine (68-86% in the
      four volunteers) was extracted by the lungs. Clomipramine decreased the lung
      uptake from 68% to 35% and from 81% to 54% in the two volunteers studied. By
      contrast, whole-brain uptake was low in control studies (1.7-2.0% in three
      volunteers) and increased after clomipramine administration (to 4.5-4.9%). Plasma
      radioactivity was also higher after clomipramine than in control studies.
      INTERPRETATION: The lungs may function as a reservoir for antidepressants with
      high affinity to the serotonin transporter. The accumulated antidepressants may
      be displaced by other antidepressants, and this displacement would substantially
      increase plasma concentrations and thus cause toxic effects.

PMID- 9652615
TI  - Wobbly handwriting.

PMID- 9652616
TI  - Cosmetic results and patient satisfaction with secondary wound healing after
      abdominal surgery.

PMID- 9652617
TI  - Is surgery useful in very old patients with intracranial meningioma?

PMID- 9652618
TI  - Pilocarpine as an adjuvant to morphine therapy.

PMID- 9652620
TI  - Acarbose-induced hepatic injury.

PMID- 9652619
TI  - Epidemic ciprofloxacin-resistant Salmonella typhi in Tajikistan.

PMID- 9652621
TI  - Injection of GABA-agonist into globus pallidus in patient with Parkinson's
      disease.

PMID- 9652622
TI  - Chlamydia trachomatis detection and the menstrual cycle.

PMID- 9652623
TI  - Subcapsular liver haematomas caused by bar ends in mountain-bike crashes.

PMID- 9652624
TI  - Gro Harlem Brundtland secures top job at WHO.

PMID- 9652625
TI  - US Public Health Service sets out plan for xenotransplantation.

PMID- 9652626
TI  - Sorting out the true from the false.

PMID- 9652627
TI  - Vector problems still thwart gene-therapy promise.

PMID- 9652628
TI  - Rebuilding the UK welfare state.

PMID- 9652629
TI  - 25 years later, US abortion war still drags on.

PMID- 9652630
TI  - Danish HIV-1 puzzle solved.

PMID- 9652631
TI  - Child claim over hazards of silicone breast implant planned in UK.

PMID- 9652632
TI  - Canadian hopes for low-cost drugs dashed.

PMID- 9652633
TI  - Hepatitis C.

PMID- 9652634
TI  - Impact of anti-vaccine movements on pertussis control: the untold story.
AB  - To assess the impact of anti-vaccine movements that targeted pertussis whole-cell
      vaccines, we compared pertussis incidence in countries where high coverage with
      diphtheria-tetanus-pertussis vaccines (DTP) was maintained (Hungary, the former
      East Germany, Poland, and the USA) with countries where immunisation was
      disrupted by anti-vaccine movements (Sweden, Japan, UK, The Russian Federation,
      Ireland, Italy, the former West Germany, and Australia). Pertussis incidence was
      10 to 100 times lower in countries where high vaccine coverage was maintained
      than in countries where immunisation programs were compromised by anti-vaccine
      movements. Comparisons of neighbouring countries with high and low vaccine
      coverage further underscore the efficacy of these vaccines. Given the safety and
      cost-effectiveness of whole-cell pertussis vaccines, our study shows that, far
      from being obsolete, these vaccines continue to have an important role in global
      immunisation.

PMID- 9652635
TI  - More than a green placebo.

PMID- 9652636
TI  - Meta-analysis of homoeopathy trials.

PMID- 9652637
TI  - Meta-analysis of homoeopathy trials.

PMID- 9652638
TI  - Meta-analysis of homoeopathy trials.

PMID- 9652639
TI  - Meta-analysis of homoeopathy trials.

PMID- 9652640
TI  - Meta-analysis of homoeopathy trials.

PMID- 9652641
TI  - Meta-analysis of homoeopathy trials.

PMID- 9652642
TI  - Meta-analysis of homoeopathy trials.

PMID- 9652643
TI  - Meta-analysis of homoeopathy trials.

PMID- 9652644
TI  - Inhaled sodium cromoglycate in young children with moderate asthma.

PMID- 9652645
TI  - Inhaled sodium cromoglycate in young children with moderate asthma.

PMID- 9652646
TI  - Granulocyte-colony-stimulating factor in diabetic foot infection.

PMID- 9652647
TI  - Left-ventricular dysfunction.

PMID- 9652648
TI  - Left-ventricular dysfunction.

PMID- 9652649
TI  - Diagnosis of fever in Africa.

PMID- 9652650
TI  - Diagnosis of fever in Africa.

PMID- 9652651
TI  - Regional node radiotherapy for breast cancer.

PMID- 9652652
TI  - Refutation of investigation commissioned by Karolinska Institute.

PMID- 9652653
TI  - Reducing disability among the elderly in Europe.

PMID- 9652654
TI  - Reducing disability among the elderly in Europe.

PMID- 9652655
TI  - False-positive self-reports of HIV-1 infection.

PMID- 9652656
TI  - Half-life of truth in medicine.

PMID- 9652657
TI  - The name of the dose.

PMID- 9652658
TI  - AIDS, the unbridgable gap.

PMID- 9652659
TI  - Can we really grow new blood vessels?

PMID- 9652660
TI  - When can an exacerbation of COPD be treated at home?

PMID- 9652661
TI  - Beta-endorphin in the immune system--mediator of pain and stress?

PMID- 9652662
TI  - What lessons can be learnt from withdrawal of mibefradil from the market?

PMID- 9652663
TI  - Treatment options in severe aplastic anaemia.

PMID- 9652664
TI  - Implications of European directive on medical devices.

PMID- 9652665
TI  - Outlook for sexually transmitted diseases.

PMID- 9652666
TI  - Spectrum of AIDS-associated malignant disorders.
AB  - BACKGROUND: To clarify which types of cancer result from AIDS, we compared the
      cancer experiences of people with AIDS with those of the general population by
      matching population-based cancer and AIDS registries in the USA and Puerto Rico.
      METHODS: We used a probabilistic matching algorithm to compare names, birth
      dates, and, where available, social-security numbers of 98,336 people with AIDS
      and 1,125,098 people with cancer aged less than 70 years. We defined AIDS-related
      cancers as those with both significantly raised incidence post-AIDS and
      increasing prevalence from 5 years pre-AIDS to 2 years post-AIDS. FINDINGS: Among
      people with AIDS, we found 7028 cases of Kaposi's sarcoma (KS), 1793 of non
      Hodgkin lymphoma (NHL), and 712 other cases of histologically defined cancer.
      Incidence rates among people with AIDS were increased 310-fold for KS, 113-fold
      for NHL, and 1.9-fold (95% CI 1.5-2.3) for other cancers. Of 38 malignant
      disorders other than KS and NHL, only angiosarcoma (36.7-fold), Hodgkin's disease
      (7.6-fold), multiple myeloma (4.5-fold), brain cancer (3.5-fold), and seminoma
      (2.9-fold) were raised and increasing significantly (p<0.02) from the pre-AIDS to
      the post-AIDS period. INTERPRETATION: Interpretation is complicated by screening
      and shared risk factors, such as sexual behaviour and cigarette smoking. However,
      our data indicate that AIDS leads to a significantly increased risk of Hodgkin's
      disease, multiple myeloma, brain cancer, and seminoma. Immunological failure to
      control herpes or other viral infections may contribute to these malignant
      diseases.

PMID- 9652667
TI  - Smoking and risk of dementia and Alzheimer's disease in a population-based cohort
      study: the Rotterdam Study.
AB  - BACKGROUND: Previous studies suggested a protective effect of smoking on
      Alzheimer's disease, but most were case-control studies based on prevalent cases.
      The findings of prospective studies on the association between smoking and the
      risk of dementia are inconclusive. METHODS: We did a population-based follow-up
      study of elderly people who were initially free of dementia. 6870 people aged 55
      years and older agreed to take part. Smoking history was taken at baseline and
      participants were classified as never smokers, former smokers, and current
      smokers. During follow-up, we recorded all incident cases of dementia. We used
      never smokers as the reference category to calculate relative risks of dementia
      and Alzheimer's disease by Cox proportional hazards regression, after adjustment
      for age, sex, education, and alcohol intake. We also examined modification of
      risk by age, sex, and the apolipoprotein E (APOE) genotype. FINDINGS: During mean
      follow-up of 2.1 (range 1.5-3.4) years, 146 incident cases of dementia were
      detected, of which 105 were Alzheimer's disease. Compared with never smokers,
      smokers had an increased risk of dementia (relative risk 2.2 [95% CI 1.3-3.6])
      and Alzheimer's disease (2.3 [1.3-4.1]). Smoking was a strong risk factor for
      Alzheimer's disease in individuals without the APOEepsilon4 allele (4.6 [1.5
      14.2]), but had no effect in participants with this allele (0.6 [0.1-4.8]).
      INTERPRETATION: Smoking was associated with a doubling of the risk of dementia
      and Alzheimer's disease. Our finding that carriers of the APOEepsilon4 had no
      increased risk of dementia suggests an interaction between smoking and the
      APOEepsilon4 genotype in the aetiology of Alzheimer's disease.

PMID- 9652668
TI  - Extended excretion of rotavirus after severe diarrhoea in young children.
AB  - BACKGROUND: Rotaviruses are the major cause of severe childhood diarrhoea.
      Knowledge of the natural history of infection, including duration of intestinal
      virus shedding, is important in the understanding of transmission, sources of
      infection, and immune responses. METHODS: We carried out a study of rotavirus
      excretion in 37 children admitted to hospital with severe rotavirus diarrhoea.
      Sequential faecal specimens were collected from each child during 100 days of
      surveillance, and screened for rotavirus by EIA and by amplification of genome
      double-stranded RNA by reverse-transcription PCR. IgA coproantibody was estimated
      by EIA. FINDINGS: Duration of rotavirus excretion ranged from 4 to 57 days after
      onset of diarrhoea. Excretion ceased within 10 days in 16 (43%) children, and
      within 20 days in 26 (70%) children. Extended excretion was detected for 25-57
      days in the remaining 11 (30%) children owing mainly to continued excretion of
      the primary infecting strain. Extended excretion was significantly associated
      with antirotavirus IgA coproantibody boosts during 100 days of surveillance
      (p=0.001, log-rank test), and with recurrence of mild diarrhoea symptoms during
      convalescence (p=0.006, Fisher's exact test). INTERPRETATION: Severe rotavirus
      disease in young children may be followed by extended excretion of rotavirus. The
      risk of transmission to others may be greater than previously believed. Extended
      excretion could also explain some cases of the postgastroenteritis syndrome.

PMID- 9652669
TI  - Metabolic abnormalities in developmental dyslexia detected by 1H magnetic
      resonance spectroscopy.
AB  - BACKGROUND: Neurological and physiological deficits have been reported in the
      brain in developmental dyslexia. The temporoparietal cortex has been directly
      implicated in dyslexic dysfunction, and substantial indirect evidence suggests
      that the cerebellum is also implicated. We wanted to find out whether the
      neurological and physiological deficits manifested as biochemical changes in the
      brain. METHODS: We obtained localised proton magnetic resonance spectra
      bilaterally from the temporo-parietal cortex and cerebellum of 14 well-defined
      dyslexic men and 15 control men of similar age. FINDINGS: We found biochemical
      differences between dyslexic men and controls in the left temporo-parietal lobe
      (ratio of choline-containing compounds [Cho] to N-acetylaspartate [NA] p< or
      =0.01) and right cerebellum (Cho/NA, p< or = 0.01; creatine [Cre] to NA p< or
      =0.05; (not significant). We found lateral biochemical differences in dyslexic
      men in both these brain regions (Cho/NA in temporo-parietal lobe, left vs right,
      p< or =0.01; Cre/NA in cerebellum, left vs right, p< or =0.001). We found no such
      lateral differences in controls. There was no significant relation between the
      degree of contralateral chemical difference and handedness in dyslexic or control
      men. INTERPRETATION: We suggest that the observed differences reflect changes in
      cell density in the temporo-parietal lobe in developmental dyslexia and that the
      altered cerebral structural symmetry in dyslexia is associated with abnormal
      development of cells or intracellular connections or both. The cerebellum is
      biochemically asymmetric in dyslexic men, indicating altered development of this
      organ. These differences provide direct evidence of the involvement of the
      cerebellum in dyslexic dysfunction.

PMID- 9652670
TI  - Home treatment of exacerbations of chronic obstructive pulmonary disease by an
      acute respiratory assessment service.
AB  - BACKGROUND: Exacerbations of chronic obstructive pulmonary disease are a major
      cause of hospital admissions, but do not require intensive investigation or
      complex therapy. We investigated the suitability of home care for severe
      uncomplicated exacerbations. METHODS: Over 3.5 years we assessed 962 patients
      with exacerbations of chronic obstructive pulmonary disease after referral to a
      hospital respiratory department by their family physicians. All patients had
      chest radiographs, oxygen-saturation or arterial-gas analysis, spirometry, and
      physical assessment. Unless admission was thought to be essential, patients were
      allowed home with a customised treatment package. Each patient was visited daily
      by a respiratory nurse who monitored progress and treatment compliance and
      provided education and reassurance. FINDINGS: 145 (15%) of 962 required admission
      at initial referral and 115 (12%) were admitted later. 653 (68%) patients were
      managed entirely at home and 49 (5%) were referred inappropriately. One patient
      died at home. All patients had severe disease with a mean forced expiratory
      volume in 1 s of 1.02 L and 395 (41%) had required hospital admission in the
      previous year. INTERPRETATION: After formal assessment in a hospital respiratory
      unit, many patients with exacerbations of chronic obstructive pulmonary disease
      can be treated at home by respiratory nurses.

PMID- 9652671
TI  - A rash, circulating anticoagulant, then meningitis.

PMID- 9652672
TI  - Resting blood pressure increase during exposure to a radio-frequency
      electromagnetic field.

PMID- 9652673
TI  - Alternative hypothesis for efficacy of macrolides in acute coronary syndromes.

PMID- 9652674
TI  - Fetal swallowing of IgE.

PMID- 9652675
TI  - Can class I epitope of M protein be a diagnostic marker for rheumatic fever in
      populations endemic for group A streptococci?

PMID- 9652677
TI  - Cystamine bislactamide: a cosmetic allergen.

PMID- 9652676
TI  - Oxindole in pathogenesis of hepatic encephalopathy.

PMID- 9652678
TI  - Mesozoic neoplasia: origins of haemangioma in the Jurassic age.

PMID- 9652679
TI  - UN adopts plans to combat worldwide illicit drug use.

PMID- 9652680
TI  - COX provides missing link in mechanism of aspirin in colon cancer.

PMID- 9652681
TI  - Sorting the hype from the facts in melanoma.

PMID- 9652682
TI  - Uzbek health care--no longer back in the USSR.

PMID- 9652683
TI  - Leaked document indicates Canada's future stance on human research.

PMID- 9652684
TI  - Spain celebrates leading the world in organ donation.

PMID- 9652685
TI  - Acne vulgaris.

PMID- 9652686
TI  - The voice of the castrato.

PMID- 9652687
TI  - Pathogenesis of HIV-1-protease inhibitor-associated peripheral lipodystrophy,
      hyperlipidaemia, and insulin resistance.
AB  - HIV-1 protease-inhibitor treatments are associated with a syndrome of peripheral
      lipodystrophy, central adiposity, breast hypertrophy in women, hyperlipidaemia,
      and insulin resistance. The catalytic region of HIV-1 protease, to which protease
      inhibitors bind, has approximately 60% homology to regions within two proteins
      that regulate lipid metabolism: cytoplasmic retinoic-acid binding protein type 1
      (CRABP-1) and low density lipoprotein-receptor-related protein (LRP). We
      hypothesise that protease inhibitors inhibit CRABP-1-modified, and cytochrome
      P450 3A-mediated synthesis of cis-9-retinoic acid, a key activator of the
      retinoid X receptor; and peroxisome proliferator activated receptor type gamma
      (PPAR-gamma) heterodimer, an adipocyte receptor that regulates peripheral
      adipocyte differentiation and apoptosis. Protease-inhibitor binding to LRP would
      impair hepatic chylomicron uptake and triglyceride clearance by the endothelial
      LRP-lipoprotein lipase complex. The resulting hyperlipidaemia contributes to
      central fat deposition (and in the breasts in the presence of oestrogen), insulin
      resistance, and, in susceptible individuals, type 2 diabetes. Understanding the
      syndrome's pathogenesis should lead to treatment strategies and to the design of
      protease inhibitors that do not cause this syndrome.

PMID- 9652688
TI  - Dissection of regional lymph nodes in cutaneous melanoma.

PMID- 9652689
TI  - Dissection of regional lymph nodes in cutaneous melanoma.

PMID- 9652690
TI  - Dissection of regional lymph nodes in cutaneous melanoma.

PMID- 9652691
TI  - Vein compliance for preoperative assessment in vascular bypass surgery.

PMID- 9652692
TI  - Chimerism in scleroderma.

PMID- 9652693
TI  - Chimerism in scleroderma.

PMID- 9652694
TI  - Stopping the Breast Cancer Prevention Trial.

PMID- 9652695
TI  - Mortality of hepatitis A in adults with hepatitis C antibodies.

PMID- 9652696
TI  - MRSA and minimally invasive treatments for benign prostatic hypertrophy.

PMID- 9652697
TI  - Postoperative cognitive dysfunction in the elderly.

PMID- 9652698
TI  - Postoperative cognitive dysfunction in the elderly.

PMID- 9652699
TI  - Safety guidelines for exercise during pregnancy.

PMID- 9652700
TI  - Fluticasone propionate for chronic obstructive pulmonary disease.

PMID- 9652701
TI  - A selective policy in follow-up for bowel cancer.

PMID- 9652702
TI  - A selective policy in follow-up for bowel cancer.

PMID- 9652703
TI  - First-ever stroke incidence.

PMID- 9652704
TI  - Medical advocacy for the oppressed.

PMID- 9652705
TI  - Medical advocacy for the oppressed.

PMID- 9652706
TI  - Medical advocacy for the oppressed.

PMID- 9652707
TI  - Screening for HIV-1 in pregnancy.

PMID- 9652708
TI  - Clinical experience of UK medical students.

PMID- 9652709
TI  - Israel's ban on Ethiopians' blood.

PMID- 9652710
TI  - On being a ginseng connoisseur.

PMID- 9652711
TI  - Global epidemiology of sexually transmitted diseases.

PMID- 9652712
TI  - Sexually transmitted diseases enhance HIV transmission: no longer a hypothesis.

PMID- 9652713
TI  - The epidemiology of global antibiotic resistance among Neisseria gonorrhoeae and
      Haemophilus ducreyi.

PMID- 9652714
TI  - Update on sexually transmitted mycoplasmas.

PMID- 9652715
TI  - Genital herpes--how much of a public-health problem?

PMID- 9652716
TI  - Is elimination of endemic syphilis transmission a realistic goal for the USA?

PMID- 9652717
TI  - Is vaccination against human papillomavirus a possibility?

PMID- 9652718
TI  - Programmes to reduce pelvic inflammatory disease--the Swedish experience.

PMID- 9652719
TI  - Advances in control of sexually transmitted diseases in developing countries.

PMID- 9652720
TI  - Do we know the effectiveness of behavioural interventions?

PMID- 9652721
TI  - Primary and secondary syphilis--United States, 1997.
AB  - Syphilis is an acute and chronic sexually transmitted disease (STD) caused by
      infection with Treponema pallidum. The disease is characterized by skin and
      mucous membrane lesions in the acute phase (primary and secondary [P&S] syphilis)
      and lesions of the bone, viscera, and cardiovascular and neurologic systems in
      the chronic phase. Because syphilis enhances transmission of human
      immunodeficiency virus (HIV), prevention of syphilis is important for controlling
      HIV. During 1986-1990, an epidemic of syphilis occurred throughout the United
      States. Syphilis rates began to decline in 1991 and have declined each year since
      that time. To determine whether this decline is reflected in changes in the
      epidemiology of syphilis, CDC analyzed notifiable disease surveillance data for
      1997. This report summarizes the findings of the analysis, which indicate that
      8551 cases of primary and secondary (P&S) syphilis were reported in 1997, an 83%
      decline in cases from the peak of the epidemic in 1990, and that syphilis remains
      substantially more common in non-Hispanic blacks than in other racial/ethnic
      groups and continues to be concentrated in the Southern region of the United
      States [corrected].

PMID- 9652722
TI  - State-specific pregnancy rates among adolescents--United States, 1992-1995.
AB  - In the United States during 1985-1990, the pregnancy rate for persons aged 15-19
      years increased 9%. From 1991 to 1992, however, the rate declined substantially
      in 31 of the 42 states for which data were available; from 1992 through 1995, the
      birth rate declined steadily, and state-specific abortion rates decreased
      annually. This report presents estimated state-specific pregnancy rates for 1992
      1995 for adolescents aged < or =19 years by age and race and the percentage
      change in state-specific pregnancy rates for persons aged 15-19 years for 1992 to
      1995. The findings indicate a downward trend in pregnancy rates for persons aged
      15-19 years during 1992-1995 for all 43 states for which data were available.

PMID- 9652723
TI  - Progress toward poliomyelitis eradication--Europe and Central Asian Republics,
      1997-May 1998.
AB  - In 1988, the World Health Assembly resolved to eradicate poliomyelitis globally
      by 2000. In 1995, the World Health Organization (WHO) European Region (EUR),
      comprising 51 member states (including Israel and the Central Asian Republics),
      accelerated efforts toward polio eradication. Improvements in status have been
      reported previously. This report summarizes progress toward polio eradication
      during 1997-1998, demonstrating that polio incidence has decreased to seven cases
      in 1997 and two cases in 1998, and surveillance has improved substantially.

PMID- 9652724
TI  - Receptor-Ck and leukemogenesis.

PMID- 9652725
TI  - Expression of cyclin D1 in mouse B cell lymphomas of different histologic types
      and differentiation stages.
AB  - The G1 cyclin, cyclin D1, has been implicated in the development of human and
      mouse tumors. Here we describe immunohistochemical analyses of cyclin D1 for a
      large panel of mouse B cell tumors. In addition, we characterize cyclin D1
      expression in a series of cultured cell lines that represent transformed B cells
      at different stages of development. Immunohistochemical analysis showed that for
      low-grade lymphomas, cyclin D1 was expressed by 83% of centroblastic centrocytic
      (CBCC) and 14% of small lymphocytic lymphomas (SLL). For high-grade tumors, 28%
      of B lymphoblastic and 23% of centroblastic tumors expressed cyclin D1, while all
      immunoblastic lymphomas were negative. Studies of RNA and protein prepared from
      cultured B lineage tumors showed that cyclin D1 was expressed by all pre-B and
      most B cell tumors but not by cell lines representative of late B cell
      differentiation or by plasma cells. Expression of cyclin D1 in the lymphomas was
      not associated with alterations in the genomic structure of the Fis-1 (Bcl-1)
      common proviral integration site or cyclin D1 itself or with cell growth activity
      as assessed by expression of proliferating cell nuclear antigen (PCNA).

PMID- 9652726
TI  - Induction of differentiation and apoptosis by dithizone in human myeloid leukemia
      cell lines.
AB  - We investigated the effect of diphenylthiocarbazone (dithizone) and its
      structurally related compounds on the differentiation and apoptosis of two human
      myeloid leukemia cell lines. Dithizone caused a time- and concentration-dependent
      induction of differentiation in both the promyelocytic leukemia cell line HL-60
      cells and the myeloblastic leukemia cell line ML-1 cells, as measured by
      nitroblue tetrazolium (NBT) reducing activity. Morphological changes and esterase
      activities confirmed that this differentiation took place. The induction of
      differentiation required the addition of dithizone to the culture medium for at
      least 12 h. The differentiation inducing activity was inhibited by the
      preincubation of dithizone with various metal ions such as Pb2+, Zn2+, Cu2+ and
      Mn2+ ions, but not with Fe3+ and Mg2+ ions. In addition, the DNA extracted from
      dithizone-treated HL-60 cells showed a typical ladder pattern characteristic of
      apoptosis in agarose gel electrophoresis. A quantitative analysis of DNA
      fragmentation revealed that this apoptosis was concentration- and time-dependent
      in both the HL-60 and ML-1 cells. Dithizone-induced apoptosis was also inhibited
      by preincubation with Mn2+ ions, but not with Mg2+ ions. These results indicate
      that dithizone induces both differentiation and apoptosis in HL-60 and ML-1 cells
      through a unique mechanism including metal chelation.

PMID- 9652727
TI  - Growth arrest associated with 12-o-tetradecanoylphorbol-13-acetate-induced
      hematopoietic differentiation with a defective retinoblastoma tumor suppressor
      mediated pathway.
AB  - The retinoblastoma tumor suppressor (Rb) gene product plays an essential role in
      cell-cycle regulation. However, its role in terminal differentiation of
      hematopoietic cells is speculative. Here we show a model of 12-o
      tetradecanoylphorbol-13-acetate (TPA)-induced hematopoietic differentiation and
      growth arrest with a defective Rb-mediated pathway. TPA treatment arrested the
      cell cycle of a human hematopoietic cell line, MEG-01s, at the G1-S boundary and
      induced expression of p21/SDI1/WAF1/CIP1 and p27/KIP1. Both of these proteins
      were present in cyclin E-associated complexes, the histone H1 and Rb kinase
      activities of which were then inactivated. However, MEG-01s cells lacked the
      intact Rb protein and the Rb-mediated pathway was defective. This model raises a
      question about the role for Rb in terminal differentiation of hematopoietic
      cells.

PMID- 9652728
TI  - Protection of leukemic cells by deoxycytidine: in vitro measures of protection
      against cytosine arabinoside.
AB  - Plasma deoxycytidine levels can be very high in leukemia patients. Such levels
      strongly protected leukemia cell lines against cytosine arabinoside (araC),
      fludarabine and 2-chlorodeoxyadenosine when using clonogenic survival as the
      endpoint. This endpoint is not easily used when studying protection in clinical
      leukemia cell samples. Therefore, we tested other ways to quantify protection
      based on biochemical measures of viability or drug metabolism. The estimates of
      the strength of protection based on rates of DNA synthesis, cellular araC uptake
      and incorporation of araC into DNA were much lower than the estimates using
      clonogenic survival. The MTT viability assay gave excellent estimates and appears
      promising for studying protection in primary leukemia cell samples.

PMID- 9652729
TI  - Cytokine gene activity in AML cells in vivo in patients.
AB  - The proliferation of acute myelogenous leukemia cells is dependent upon cytokine
      stimulation. Additionally, there is a body of literature which reports that
      leukemia cells produce GMCSF, IL6, and other cytokines. The study reported here,
      using an rt-multiplex polymerase method, determined the presence or absence of
      transcripts in freshly obtained AML cells for the following cytokine or cytokine
      related genes: IL 1beta, IL1ra, TNF alpha, GMCSF, IL6, flt 3, and hSCF. This
      demonstrated that leukemia cell populations usually contain transcripts for
      IL1beta, TNF alpha, flt 3 and flt 3 ligand in vivo and that transcripts for the
      other cytokines only appear after the leukemia cells are processed in vitro. The
      presence of TNF alpha transcripts appears to be associated with resistance to
      remission induction therapy. Furthermore, the transcript profile of the leukemia
      cells can change during remission induction therapy. The data also demonstrate
      the assessment of cytokine production by leukemia cells after in vitro
      manipulation should not be extrapolated to the in vivo situation.

PMID- 9652730
TI  - Flow cytometric assessment of three different methods for the measurement of in
      vitro apoptosis.
AB  - Chlorambucil-induced apoptosis was assessed by three different flow cytometric
      methods in B-cell chronic lymphocytic leukaemia (B-CLL) cells cultured in vitro
      and the results were compared with those derived from the morphological
      assessment of the same samples. Spontaneous apoptosis was consistently observed
      in the control cultures in the absence of drug but this accounted for less than
      12% of all cells in every case. The methods under investigation were the Annexin
      V labelling assay, the terminal deoxynucleotidyl transferase (TdT) end-labelling
      assay and the labelling of a 38 kDa mitochondrial membrane protein (7A6 antigen)
      which is exposed on cells undergoing apoptotic cell death (Apo2.7 assay). The
      Annexin V assay consistently stained a higher percentage of cells and with a
      greater separation between the positive and negative cell populations. We
      conclude that the phosphatidyl serine translocation to the outer leaflet of the
      cell membrane following an apoptotic signal, as labelled by Annexin V, probably
      occurs before the development of the DNA strand breaks or the exposure of 7A6
      antigen in those cells triggered to die by apoptosis.

PMID- 9652731
TI  - Tobacco, alcohol, diet and risk of non-Hodgkin's lymphoma: a case-control study
      in Uruguay.
AB  - To test whether high meat intake is associated with the development of non
      Hodgkin lymphoma (NHL) in the Uruguayan population, a case-control study was
      performed at the Instituto Nacional de Oncologia, Montevideo, Uruguay. After
      controlling for age, sex, residence, education, urban/rural status and the habit
      of drinking the beverage 'mate', red meat intake was associated with an increased
      risk of NHL of 2.5. This finding was similar in both sexes separately. Odds
      ratios (OR) for the highest tertile of barbecued meat was 1.7 among men, whereas
      salted meat was associated with an increased risk of NHL (OR 4.9, 95% CI 1.4
      17.7). The effect of processed and salted meat among women was of much less
      magnitude and the OR's were non-significant. Also, cumulative exposure to 'mate'
      drinking displayed an OR of 2.4 (95% CI 1.0-5.6). Smokers of black tobacco and
      hand-rolled cigarettes were associated with an increased risk of 3.5 (95% 1.1
      10.9), whereas beer drinkers showed an increased OR of 5.5 (95% 1.1-26.7) in men.
      It could be concluded that red or salted meat intake, smoking of black tobacco,
      and beer and 'mate' drinking are risk factors for NHL in the Uruguayan
      population.

PMID- 9652732
TI  - Myelodysplastic syndromes in Thailand: a retrospective pathologic and clinical
      analysis of 117 cases.
AB  - To gain more insight into the understanding of myelodysplastic syndromes (MDS) as
      they occur in Thailand, a retrospective clinicopathologic analysis was conducted
      in patients (age > 15 years) diagnosed as MDS from January 1992 to December 1996
      at the five major medical centers in various geographic regions of the country.
      The central reviewers independently examined the bone marrow and peripheral blood
      smears of all the patients and classify the disease according to the French
      British-American (FAB) classification. There were a total of 117 eligible
      patients. The median age of the patients was 56 years (range 16-86). The
      male:female ratio was 1:1. Thirty-two percent of the patients were younger than
      40 years. The frequency of the FAB subtypes was RA/RARS, 54.7; RAEB, 23.1; CMML,
      9.4; and RAEB-T, 12.8%. Anemia was the most common symptom presenting in 84.6% of
      the patients. In the 34 patients in whom the cytogenetics in the bone marrow were
      analysed, 44.1% revealed abnormalities. Of these, monosomy 7 and trisomy 8 were
      the most common aberration, each being detected in 26.7% of the patients.
      Transfusions were the main therapeutic modality in 80% of the patients. Kaplan
      Meier analysis revealed a 5 year survival rate of 29% for the whole group with a
      median survival of 24 months. Twenty-five percent of the patients had progressed
      to acute myelogenous leukemia (AML) with a median time to disease-progression of
      23 months. The median survival for RA/RARS, RAEB, CMML and RAEB-T were 58.4,
      19.9, 10.7 and 8.7 months, respectively (P < 0.001). The stepwise Cox regression
      analysis revealed the percentage of blasts in the bone marrow as the only
      parameter significantly associated with survival and disease progression. On
      comparison with data from other countries, the age of Thai patients with MDS is
      considerably lower than the western population but is comparable to other asian
      countries. The distribution of the FAB subtypes and the survival of the patients
      are similar. The major prognostic features, however, lie in the percentage of
      blasts in the bone marrow rather than the degree of the observed cytopenia.

PMID- 9652733
TI  - Lack of TEL/AML1 fusion in pediatric AML: further evidence for lineage
      specificity of TEL/AML1.
AB  - BACKGROUND: The TEL/AML1 fusion associated with t(12;21)(p13;q22) is the most
      common gene rearrangement in childhood malignancy, occurring in approximately 25%
      of pediatric acute lymphoblastic leukemia. The TEL/AML1 rearrangement is cryptic
      at the cytogenetic level but confers a favorable prognosis. The AML1 gene was
      first identified by virtue of its involvement in adult and pediatric acute
      myeloid malignancies associated with t(8;21) and t(3;21)(q26;q22.1). We have
      therefore determined the frequency of the TEL/AML1 fusion in pediatric myeloid
      leukemias by RT-PCR analysis. METHODS: Total RNA was isolated from cryopreserved
      bone marrow samples of 38 pediatric patients with AML. RNA quality was controlled
      for by amplification of the TEL gene. An RT-PCR assay was then used to test for
      the presence of the TEL/AML1 fusion. RESULTS: 29 patients had adequate RNA for
      analysis. Zero out of 29 pediatric AML patients had evidence for the TEL/AML1
      fusion by RT-PCR. CONCLUSIONS: The TEL/AML1 fusion does not occur in children
      with AML and suggests that the TEL/AML1 rearrangement is restricted in pediatric
      hematologic malignancy to B lineage ALL.

PMID- 9652735
TI  - Fournier's gangrene as first presentation of promyelocytic leukemia.
AB  - A 50-year-old male is described who presented with Fournier's gangrene as what is
      probably the first manifestation of a newly diagnosed acute myelogenous leukemia
      (AML), promyelocytic type or variant type M3 according to the FAB classification.
      Despite aggressive fluid resuscitation, tuned infusion of vasoactive drugs,
      appropriate antibiotics and extensive surgical debridement, the patient died
      within 24 h as a result of irreversible septic shock.

PMID- 9652734
TI  - Acute myelogenous leukemia in Down's syndrome: report of a single pediatric
      institution using a BFM treatment strategy.
AB  - Between July 1990 and December 1995, 111 new consecutive pediatric patients with
      acute myelogenous leukemia (AML) have been treated in our institution. Eleven of
      them (9.9%) had Down's syndrome (DS), 6 boys and 5 girls. The median age was 22.5
      (range 10-40) months. FAB subtypes were the following: M7: 6, M4: 3, and M0: 2.
      Five of them had previously had myelodysplasia and in 3, all FAB M7,
      myelofibrosis was detected. This population was treated with two consecutive
      protocols. Nine patients were included in the AML-HPG-90 protocol and 2 patients
      in the AML-HPG-95 study, respectively. However, all DS patients in this series
      received the same treatment. Eight patients achieved complete remission: two
      patients received two cycles of intensification with high dose (HD) ara-C, and 1
      patient, only one cycle; the other 5 were prevented from receiving such therapy
      because of unacceptable toxicity or death. At 45 months, event-free survival and
      overall survival estimates were 0.30, S.E. 0.16. Mortality was remarkably high.
      All deaths (7) were associated with sepsis (5) or pulmonary infection (2). Three
      deaths occurred before achieving complete remission, 3 patients died during the
      consolidation phase and 1 died whilst off treatment. No one presented leukemic
      relapse. We conclude that this AML-BFM treatment strategy is highly toxic to
      children with DS and AML in our setting. Efforts will be made to improve clinical
      support and to administer less intensive therapy to this particular pediatric AML
      subgroup, which, in fact, has a better prognosis than the same non-trisomic
      population.

PMID- 9652736
TI  - Functional interplay between p53 and E2F through co-activator p300.
AB  - Both E2F and p53 are sequence specific transcription factors that regulate early
      cell cycle progression. The pathway of control mediated through E2F governs the
      transition from G1 into S phase whereas p53 in response to genotoxic stress can
      facilitate cell cycle arrest or apoptosis. The mechanisms which influence the
      outcome of p53 induction are not clear, although transcription of the p53 target
      gene, encoding the cdk-inhibitor p21(Waf1/Cip1), correlates with p53-mediated
      cell cycle arrest. Here using a combination of biochemical and functional assays
      we identify p300 as a co-activator required for p53-dependent transcriptional
      activation of Waf1/Cip1. Furthermore, we show that the cdk-inhibitor
      p21(Waf1/Cip1) autoregulates in a positive fashion transcription through
      modulating the activity of the p53/p300 complex, whilst negatively regulating the
      activity of E2F by preventing cdk-dependent phosphorylation of pRb. Consistent
      with a role for p21(Waf1/Cip1) in the autoregulation of p53-dependent
      transcription, p300 augments the ability of p53 to cause G1 arrest and,
      conversely, cells undergoing p53-dependent apoptosis are rescued by p300. Thus,
      our data suggest that the ability of p300 to interact with p53 influences the
      physiological consequence of p53 activation. From previous studies it is known
      that cells expressing aberrant levels of E2F-1 can undergo p53-dependent
      apoptosis. In addition, we find that E2F-1 can cause apoptosis in p53-/- tumour
      cells and further p300, which also functions as a co-activator for the E2F/DP
      heterodimer, enhances the apoptotic activity of E2F-1. In conditions where E2F-1
      and p53 co-operate in apoptosis E2F-1 can effectively compete for p300, causing a
      reduction in p53-dependent transcription. Thus, a functional interaction between
      p300 and either p53 or E2F-1 has a profound impact on early cell cycle
      progression, specifically in regulating the contrasting outcomes of cell cycle
      arrest and apoptosis. These results suggest a critical role for p300 in
      integrating and co-ordinating the functional interplay between the pathways of
      growth control mediated by E2F and p53.

PMID- 9652738
TI  - Hypomethylation and increased gene expression of p16INK4a in primary and
      metastatic breast carcinoma as compared to normal breast tissue.
AB  - Controversy continues to surround the role of p16INK4a in cell cycle control and
      carcinogenesis. Mutations, deletions and changes in methylation patterns of
      p16INK4a have been proposed as mechanisms leading to abnormal expression of the
      gene. We show here that primary and metastatic breast carcinomas demonstrate
      hypomethylation of p16INK4a which is associated with expression of p16INK4a mRNA,
      as compared to normal breast tissue which demonstrates a relative
      hypermethylation of p16INK4a associated with the absence of p16INK4a expression.
      These data suggest that methylation and lack of expression of p16INK4a is not a
      central mechanism in the development of breast carcinoma, but rather that the
      gene is functioning and expressed in breast carcinoma more frequently than in
      normal breast tissue. The role of p16INK4a is much more complex than has been
      previously hypothesized.

PMID- 9652737
TI  - Expression of dominant negative Jun inhibits elevated AP-1 and NF-kappaB
      transactivation and suppresses anchorage independent growth of HPV immortalized
      human keratinocytes.
AB  - AP-1 transactivation appears to be required for mouse JB6 cell neoplastic
      transformation induced by the tumor promoter TPA or epidermal growth factor
      (EGF). Exposure to AP-1 transrepressing retinoids and glucocorticoids and
      expression of a dominant negative c-jun (TAM67) blocked tumor promoter-induced AP
      1 transactivation and neoplastic transformation. The aim of the present study was
      to extend the inquiry of the role of AP-1 and other transcription factors to
      human neoplastic progression. Expression of human papillomavirus (HPV) 16 or 18
      E6 and E7 immortalizes human keratinocytes and inhibits serum/calcium-stimulated
      differentiation. Further transformation by v-fos co-expression renders these
      keratinocytes tumorigenic in nude mice. We have analysed two series of E6/E7
      immortalized human keratinocyte cell lines that show progressing phenotypes
      ranging from differentiation sensitive to anchorage-independent to tumorigenic in
      nude mice. We analysed the activities of AP-1 and NF-kappaB which may 'cross
      talk'. Both DNA binding and transactivation of AP-1 and NF-kappaB transcription
      factors showed elevation in the anchorage-independent (16RH) and tumorigenic (18
      v-fos) keratinocyte lines compared to the less progressed but immortalized cell
      lines. HPV E7 was expressed at a constant level shown by quantitative RT-PCR in
      both the more and the less progressed lines, indicating that E7 is not the factor
      limiting this progression. Blocked shift/supershift analysis indicates that Fos
      family member proteins especially Fra-1 and Fra-2 are related to progression and
      no changes found in the Jun family member proteins although they are present in
      the AP-1/DNA binding complex. When a dominant negative mutant c-jun driven by a
      human keratin 14 promoter was co-transfected with AP-1 or NF-kappaB reporters,
      both AP-1 and NF-kappaB activities were suppressed in the more progressed cell
      lines 16RH and 18 v-fos but not in the less progressed 16RL or 18 cell lines.
      Overexpression of the same dominant negative c-jun did not inhibit p53 dependent
      reporter transactivation, indicating the specificity of inhibition of AP-1 and NF
      kappaB transactivation in the HPV-immortalized cells. Stable transfectants of
      this mutant c-jun in the two more progressed cell lines 16RH and 18 v-fos showed
      reduced AP-1 and NF-kappaB activation and reduced anchorage-independent growth.
      Together, these results indicate that activation of AP-1, NF-kappaB or both may
      contribute to neoplastic progression in HPV immortalized human keratinocytes and
      that specific targeting of the elevated levels seen in benign or malignant tumors
      might be effective for prevention or treatment of human cancer.

PMID- 9652739
TI  - Retinoblastoma protein-overexpressing HL60 cells resistant to 1,25
      dihydroxyvitamin D3 display increased CDK2 and CDK6 activity and shortened G1
      phase.
AB  - Drug resistance that occurs during cancer chemotherapy has been a major problem
      in controlling neoplastic progression. To study the cellular mechanisms of
      acquired drug resistance we developed 1,25-dihydroxyvitamin D3 (1,25D3)-resistant
      sublines of promyelocytic leukemia HL60 cells which have increased proliferation
      rates (Exp. Cell Res., 224, 312, 1996; Cancer Res., 50, 5513, 1996). We report
      here that the resistant sublines display varying degrees of shortening of the G1
      phase as compared to the parental HL60-G cells. Protein levels of cyclins E, D1,
      D2 and D3 are elevated in these resistant cell lines, and cyclin D1 is especially
      high in 40AF cells, which has the shortest G1 length. The protein levels of
      cyclin-dependent kinase (Cdk)2, Cdk4 and Cdk6 are not altered in the resistant
      sublines. Both Cdk2 and Cdk6-associated kinase activites are increased in the
      resistant sublines, but not Cdk4 kinase activity. Protein levels of p27Kip1 are
      not consistently altered in the resistant sublines as compared to the parental
      HL60-G cells, but are reduced relative to HL60-G cells arrested by 96 h treatment
      with 1,25D3. Interestingly, the resistant cell lines constitutively express high
      levels of retinoblastoma protein (pRb), and pRb is highly phosphorylated,
      indicating that the G1 cyclin/Cdk complexes in the resistant cells are
      physiologically active. The results suggest that the increased activity of cyclin
      D/Cdk6, and perhaps cyclin E/Cdk2, lead to rapid hyperphosphorylation of pRb and
      consequently a shorter early G1 phase, and that in the resistant cells the
      increased ratio of cyclin E to p27Kip1 results in activation of Cdk2 and
      contributes to the abrogation of the 1,25D3-induced block to the S phase entry.
      Additionally, it is apparent that constitutively increased levels of pRb are
      compatible with increased rates of cell proliferation.

PMID- 9652740
TI  - The BPV-4 co-carcinogen quercetin induces cell cycle arrest and up-regulates
      transcription from the LCR of BPV-4.
AB  - Bracken fern is the environmental co-carcinogen of BPV-4 in the induction of
      neoplasias of the upper alimentary canal of cattle. The flavonoid quercetin is
      one of the most potent and best characterised mutagens present in the fern. We
      have shown that transfection with BPV-4 DNA and exposure to a single dose of
      quercetin leads to tumorigenic transformation of primary bovine cells. We now
      show that quercetin induces cell cycle arrest and up-regulates transcription from
      the BPV-4 long control region (LCR). This up-regulation is mediated by a 21
      nucleotide-long cis-element in the LCR, designated QRE-1, which is located
      immediately downstream of the TATA box. Cellular proteins bind to QRE-1 and
      removal or substitution of QRE-1 lead to the abrogation of the response to
      quercetin. As expression of the viral oncogenes is controlled by the LCR,
      perturbation in this control and increased oncoprotein expression are likely to
      contribute to fully malignant cell transformation by overcoming the cell cycle
      arrest induced by quercetin, thus forcing damaged cells to proliferate.

PMID- 9652741
TI  - Allelic loss analysis of gamma-ray-induced mouse thymic lymphomas: two candidate
      tumor suppressor gene loci on chromosomes 12 and 16.
AB  - A total of 429 gamma-ray-induced thymic lymphomas were obtained from F1 and
      backcross mice between BALB/c and MSM strains, about a half of which carried a
      p53-deficient allele. A genome-wide allelic loss analysis has revealed two loci
      exhibiting frequent allelic losses but no allelic preference, one is localized
      within a 2.9 cM region between D12Mit53 and D12Mit279 loci on chromosome 12, and
      the other is near the D16Mit122/D16Mit162 loci on chromosome 16. The frequency of
      allelic loss in the D12Mit279 region is 62% and does not differ in tumors between
      the presence and absence of the p53-deficient allele. In contrast, the loss
      frequency of D16Mit122 is raised by the existence of p53-deficient allele: 62%
      for p63(-/+) and 13% for p53(+/+), suggesting co-operative function of the two
      losses. The D12Mit279 and D16Mit122 regions probably harbor different types of
      tumor suppressor gene that play key roles in lymphoma development.

PMID- 9652742
TI  - Myc/p53 interactions in transgenic mouse mammary development, tumorigenesis and
      chromosomal instability.
AB  - We have examined defects in mammary development and tumorigenesis in a transgenic
      model expressing the c-myc gene under the MMTV-LTR promoter. The stochastic
      tumors which arise from hyperplastic ductal and lobular lesions in this model are
      characterized by high rates both of apoptosis and of chromosomal instability.
      Since the p53 gene product is thought to be central in the maintenance of genomic
      integrity, in part due to its ability to induce apoptosis in cells harboring DNA
      damage, we examined its expression and possible mutation. Initially, we observed
      that unmutated p53 is strongly expressed in premalignant mammary glands and in
      mammary tumors derived from the MMTV-c-myc strain. We then mated the MMTV-myc
      strain to a p53-deficient strain as a means of examining the effect of this
      lesion on mammary development and tumorigenesis in the context of c-myc
      overexpression. A lack of both p53 alleles in the presence of c-myc
      overexpression resulted in a dramatic hyerplastic alteration in mammary gland
      development. Specifically, in female bitransgenic MMTV-c-myc/p53 null mice (MMTV
      myc/p53(-/-)), lobular hyperplasias were observed at almost every ductal end bud
      as early as 32 days of age. In contrast, only mild ductal and lobular
      hyperplasias were seen in MMTV-myc mice that contained both p53 alleles (MMTV
      myc/p53(+/+)); an intermediate phenotype occurred in mice with a single intact
      (MMTV-myc/p53(+/-)) p53 allele. Mammary carcinomas arose with a high frequency in
      MMTV-myc/p53(+/-) mice; the tumors were comparable in frequency, histology and
      apoptotic index to the tumors in MMTV-myc/p53(+/+) mice. Also, as previously
      observed (Elson et al., 1995), lymphomas arose with extremely short latency in
      MMTV-myc/p53(-/-) mice, precluding study of the fate of their hyperplastic
      mammary lesions in situ. The frequency of p53 mutations in MMTV-myc/p53(+/+) and
      MMTV-myc/p53(+/-) mammary tumors and in cell lines derived from these tumors was
      examined by direct sequencing. No point mutations or deletions in p53 were
      observed in mammary tumors or cell lines from either genotype. Finally, a
      detailed chromosomal analysis using multicolor spectral karyotyping (SKY)
      revealed that there were multiple chromosomal alterations in the c-myc
      overexpressing cells that contained either one or two unmutated p53 alleles.
      Variable ploidy changes, a common translocation of chromosome 11, and other
      chromosomal aberrations were observed. Our data thus support an interaction
      between c-Myc and p53 in mammary development, but suggest that loss of p53 is
      required neither for c-myc-dependent tumorigenesis nor for c-myc-dependent
      chromosomal instability.

PMID- 9652743
TI  - Mutations at coding mononucleotide repeats in gastric cancer with the
      microsatellite mutator phenotype.
AB  - We analysed 50 gastric carcinomas (GCs) to verify whether mutations at coding
      repeats were associated with microsatellite instability (MSI). The tumors
      included: ten cases with no MSI, 14 cases with MSI = 1 locus, 13 cases with MSI =
      two loci and 13 cases with MSI > or = 3 loci. We investigated coding repeats
      within the TGF-beta RII, IGFIIR, BAX, hMSH6, hMSH3 and BRCA2 genes. The TGF-beta
      RII, IGFIIR, BAX, hMSH6 and hMSH3 repeats were altered in 11 (22%), five (10%),
      four (8%), 16 (32%) and five (10%) cases respectively. Mutations occurred only in
      MSI-positive (MSI+) tumors and correlated with increasing MSI levels. No
      alterations of the BRCA2 repeat were found. Mutations in genes other than hMSH6
      were strongly associated to hMSH6 mutations, suggesting a key role of this gene.
      The non-coding BAT-26 and E-Cadherin 3' UTR poly(A)8/(T)15 repeats were analysed
      in 44 of the 50 cases. Novel tumor-associated alleles were observed only in MSI
      positive GCs and were in most cases associated with mutations at coding repeats.
      Further investigations with BAT-40 confirmed that four cases manifested
      mononucleotide repeat alterations restricted to hMSH6 and one case to TGF-beta
      RII. A subset of tumors with MSI at two or more dinucleotide loci resulted
      negative for mutations at coding and non-coding mononucleotide repeats.

PMID- 9652744
TI  - Tec is involved in G protein-coupled receptor- and integrin-mediated signalings
      in human blood platelets.
AB  - Tec is a non-receptor type tyrosine kinase which is tyrosine phosphorylated and
      activated upon stimulation of hematopoietic cells with various cytokines. The
      role of Tec in G protein-coupled receptor- and integrin-mediated signalings has
      not been elucidated. We therefore investigated the regulation of Tec in human
      blood platelets. Tec was rapidly tyrosine phosphorylated in response to platelet
      agonists which activate G protein-coupled receptors such as thromboxane A2 analog
      (U46619), thrombin, and thrombin receptor activating peptide (TRAP). TRAP-induced
      phosphorylation in Tec was significantly reduced under the conditions which
      abrogate fibrinogen binding to GP IIb-IIIa and subsequent platelet aggregation.
      However, TRAP induced significant levels of the phosphorylation even under these
      conditions and also in thrombasthenic platelets which lack functional GP IIb-IIIa
      molecules, suggesting that activation of G-protein-coupled receptor causes the
      phosphorylation. To clarify whether integrin engagement by itself causes the
      phosphorylation in Tec, we examined the state of the phosphorylation in platelets
      activated by integrin engagement. Platelet adhesion to immobilized fibrinogen or
      collagen induced significant levels of the phosphorylation. Furthermore, Tec was
      translocated to cytoskeleton in response to TRAP in a manner dependent on
      platelet aggregation, suggesting that Tec can be a component of integrin-mediated
      signalings. These results collectively indicate that Tec is involved in G protein
      coupled receptor- and integrin-mediated signalings in human blood platelets.

PMID- 9652745
TI  - Isolation of a new protein factor required for activation of Raf-1 by Ha-Ras:
      partial purification from rat brain cytosols.
AB  - Ras-mediated signaling pathways play a critical role in cellular proliferation
      and differentiation. Although it has been demonstrated that Ras interacts with
      Raf-1 to stimulate the serine/threonine kinase activity of Raf-1, the precise
      mechanism by which Ras activates Raf-1 remains obscure. To address this question,
      we developed a cell-free system in which the activated form of H-Ras can induce
      Raf-1 activation. Using this system, we found the presence of a new protein
      factor, in cytosolic fractions of both human embryonic kidney 293 cells and rat
      brain tissues, that is required for Ras-dependent activation of Raf-1. The factor
      was purified from rat brain cytosols through successive column chromatographies
      on DEAE Sephacel, SP Sepharose and Sephacryl S-300. The approximate molecular
      weight of the activator was estimated as 400,000 by gel filtration. Its activity
      was sensitive to heat and trypsin treatments. The purified activator did not
      contain Src, 14-3-3, protein kinase C, JAK2 or Ksr-1, as judged by
      immunoblotting. Further characterization of the activator is underway.

PMID- 9652746
TI  - Inhibition of the mitogen activated protein (MAP) kinase cascade potentiates cell
      killing by low dose ionizing radiation in A431 human squamous carcinoma cells.
AB  - The molecular mechanism(s) by which tumor cells survive after exposure to
      ionizing radiation are not fully understood. Exposure of A431 cells to low doses
      of radiation (1 Gy) caused prolonged activations of the mitogen activated protein
      (MAP) kinase and stress activated protein (SAP) kinase pathways, and induced
      p21(Cip-1/WAF1) via a MAP kinase dependent mechanism. In contrast, higher doses
      of radiation (6 Gy) caused a much weaker activation of the MAP kinase cascade,
      but a similar degree of SAP kinase cascade activation. In the presence of MAP
      kinase blockade by the specific MEK1 inhibitor (PD98059) the basal activity of
      the SAP kinase pathway was enhanced twofold, and the ability of a 1 Gy radiation
      exposure to activate the SAP kinase pathway was increased approximately sixfold
      60 min after irradiation. In the presence of MAP kinase blockade by PD98059 the
      ability of a single 1 Gy exposure to cause double stranded DNA breaks (TUNEL
      assay) was enhanced at least threefold over the following 24-48 h. The increase
      in DNA damage within 48 h was also mirrored by a similar decrease in A431 cell
      growth as judged by MTT assays over the next 4-8 days following radiation
      exposure. This report demonstrates that the MAP kinase cascade is a key
      cytoprotective pathway in A431 human squamous carcinoma cells which is activated
      in response to clinically used doses of ionizing radiation. Inhibition of this
      pathway potentiates the ability of low dose radiation exposure to induce cell
      death in vitro.

PMID- 9652747
TI  - Imprinted M6p/Igf2 receptor is mutated in rat liver tumors.
AB  - We have previously shown that inactivation of mannose 6-phosphate/insulin-like
      growth factor 2 receptor (M6P/IGF2R) is a common early event in both human liver
      and breast carcinogenesis. The M6p/Igf2r is imprinted in mice while expression is
      biallelic in most humans. In this investigation the M6p/Igf2r gene is shown to
      also be imprinted in the liver of Fischer 344, Lewis and Brown Norway rats. In
      addition, we have identified mutations in the expressed allele of the M6p/Igf2r
      in 40% of diethylnitrosamine-initiated rat liver tumors. These results provide
      further evidence that the M6P/IGF2R functions as a liver tumor suppressor gene.
      They also suggest that mice and rats would be more sensitive than humans to those
      hepatocarcinogens in which the M6p/Igf2r is mechanistically involved in
      transformation since one rather than two alleles would need to be inactivated.

PMID- 9652748
TI  - Inhibition of the MAP kinase cascade blocks heregulin-induced cell cycle
      progression in T-47D human breast cancer cells.
AB  - Members of the erbB family of receptor tyrosine kinases are commonly
      overexpressed in human breast cancer. However, the relative contribution of
      particular signalling pathways activated downstream of these receptors to the
      mitogenic response of transformed breast epithelial cells remains poorly
      characterized. Administration of heregulin-beta2 (HRG), a ligand for erbB3 and
      erbB4, to growth arrested T-47D human breast cancer cells leads to activation of
      both the PI3-kinase and MAP kinase signalling pathways and potent stimulation of
      cell cycle progression. Specific inhibitors were used to assess the role of these
      pathways in HRG-induced mitogenesis and to identify underlying mechanisms in
      terms of regulation of gene expression. Treatment with the MEK inhibitor PD98059
      led to a complete block of HRG-induced entry into S-phase, whilst administration
      of the PI3-kinase inhibitor wortmannin resulted in only modest inhibition. In
      addition, administration of PD98059 8 h after HRG was equipotent with
      simultaneous administration in inhibiting entry into S-phase. However, delaying
      addition for 14-16 h after HRG, when the cells were entering S-phase, was without
      effect. HRG stimulation led to sequential induction of c-myc, cyclin D1, cyclin E
      and cyclin A gene expression and hyperphosphorylation of the retinoblastoma
      protein pRB. p21 (WAF1/CIP1/SDI1) gene expression was rapidly induced by HRG, but
      significant changes in p27 (KIP1) protein levels were not detected. Preincubation
      with PD98059 blocked the HRG-dependent induction of cyclin D1 mRNA, p21 and c-Myc
      protein and pRB phosphorylation. These findings demonstrate that MEK activation
      is critical to HRG-induced S-phase entry in these cells whilst PI3-kinase plays a
      minor role. Moreover, these data are compatible with HRG-induced activation of
      MEK being critical for a mid-G1 transition point and implicate c-myc and cyclin
      D1 as key targets of the MAP kinase pathway involved in this response.

PMID- 9652749
TI  - Absence of TSG101 transcript abnormalities in human cancers.
AB  - The human TSG101 gene was cloned and mapped to chromosome 11p15, a site suspected
      to contain a tumor suppressor gene involved in a variety of human cancers.
      Subsequent investigation described the presence of abnormally spliced transcripts
      and point mutations of TSG101 in breast cancer. Thus, we performed RT-PCR
      amplification of the entire open reading frame of TSG101 to test for aberrant
      transcripts in various human tumor cell lines derived from breast, bladder, head
      and neck, and lung cancer. In addition, we performed RT-PCR on cDNA from primary
      human breast and Wilms' tumor tissue. We found a single band of the expected size
      in 10 of 11 breast cancers and 6 of 6 Wilms' tumor samples after the first round
      of PCR. The remaining breast cancer sample displayed a barely visible smaller
      band. However, aberrant bands appeared in most cases after performing nested PCR
      casting doubt on the physiologic relevance of these spliced variants. We then
      searched for small intragenic mutations by complete sequence analysis of TSG101
      in breast cancer cell lines and tumors, as well as in Wilms' tumors and normal
      fetal and adult kidney. No point mutations were found in any of the samples,
      including four breast tumors with chromosomal loss at 11p15. We found no
      consistent evidence of aberrant splicing or point mutations in breast cancer or
      Wilms' tumor suggesting that TSG101 is not a primary target of inactivation in
      human cancer.

PMID- 9652750
TI  - Characterization of Wnt-1 and Wnt-2 induced growth alterations and signaling
      pathways in NIH3T3 fibroblasts.
AB  - Members of the Wnt family induce mouse mammary tumors and partially transform
      mammary epithelial cells in culture. However, their mechanism of transformation
      remains to be elucidated. In NIH3T3 mouse embryo fibroblasts, a standard
      transformation model, Wnt-1 and Wnt-2 were shown to induce altered properties
      including increased saturation density and growth in soft agar. Such cells also
      exhibited increased cell-cell adhesiveness. However, unlike oncogenes such as
      PDGFB or ras, Wnt-1 and -2 failed to induce detectable transformed foci following
      transfection, and stable NIH3T3 transfectants lacked tumor forming capacity. Wnt
      1 and -2 transfectants exhibited increased uncomplexed, cytosolic beta-catenin,
      which was not observed with PDGFB, ras or erbB2 transfectants. In transient
      transfection, Wnt-1 and -2 induced a rapid increase in cytosolic beta-catenin but
      no detectable increase in the phosphorylated activated forms of MAP kinase. In
      contrast, ras was a potent activator of MAP kinase but had no effect on free beta
      catenin levels. These findings establish that both Wnt signaling and pattern of
      growth alterations differ from those of oncogenes which activate proliferative
      signaling pathways in NIH3T3 cells.

PMID- 9652751
TI  - Inhibitory effects of malotilate on invasion and metastasis of rat mammary
      carcinoma cells by modifying the functions of vascular endothelial cells.
AB  - Malotilate (diisopropyl,1,3-dithiol-2-ylidenemalonate, MT) is clinically used as
      a hepatoprotective agent. Because we noticed that MT induced the differentiation
      of cultured vascular endothelial cells, we have examined its effects on lung
      metastasis of the highly metastatic rat mammary carcinoma c-SST-2. MT was orally
      administered to syngeneic SHR rats from 7 days before or after s.c. inoculation
      of c-SST-2 cells to the end of the experiments. In the MT-treated rats, pulmonary
      metastasis was markedly suppressed compared with the non-treated rats. In the
      rats treated with MT for 19 days after i.v. inoculation of c-SST-2 cells, lung
      metastasis was also significantly suppressed. An in vitro invasion assay using a
      rat lung endothelial (RLE) cell monolayer revealed that pretreatment of the RLE
      cells with MT, but not c-SST-2 cells, significantly reduced the invasion of the
      RLE monolayer by c-SST-2 cells. An in vitro vascular permeability assay
      demonstrated that MT prevented the increase in permeability of the RLE monolayer
      by serum starvation. On the other hand, in vivo and in vitro growth, gelatinase
      production and adhesion to the RLE cell monolayer of c-SST-2 cells were not
      affected by MT treatment. These findings suggest that MT suppressed tumour
      metastasis by intensifying the cell-to-cell contact of endothelial cells, thus
      preventing tumour cells from invading vascular endothelium.

PMID- 9652752
TI  - Induction of apoptosis by taxol and cisplatin and effect on cell cycle-related
      proteins in cisplatin-sensitive and -resistant human ovarian cells.
AB  - The effect of taxol (TX) and cisplatin (CDDP), singly or in association, was
      assessed on two human ovarian cancer cell lines, one sensitive (A2780) and one
      resistant (A2780 cp8) to CDDP. Cell lines showed a similar sensitivity to TX,
      whereas different cytotoxicity results were obtained in the two cell lines as a
      function of TX and CDDP sequence. Specifically, TX followed by CDDP induced
      simply additive effects in both cell lines, whereas the opposite sequence
      produced antagonistic effects in A2780 cells and synergistic effects in A2780 cp8
      cells. TX, with or without CDDP, induced oligonucleosomal DNA fragmentation
      typical of the apoptotic process, but the biochemical mechanisms undergoing
      apoptosis were different in the two cell lines. In fact, in A2780 cells, TX (with
      or without CDDP) treatment markedly increased p53 as well as p21waf1 protein
      expression. In A2780 cp8 cells, drug treatment enhanced p53 levels, whereas the
      expression of p21waf1 was always undetectable at mRNA and protein levels. In the
      latter cell line, a premature activation of p34cdc2 kinase was observed in
      correspondence with the drug-induced increase in the S-phase cell fraction. Such
      an activation was not ascribable to an increase in the overall expression of
      p34cdc2 or cyclin B1 proteins, but to a dephosphorylation of p34cdc2 kinase.
      Overall, our results indicate that TX-induced apoptosis in human ovarian cancer
      cells may be sustained by different events at the cell cycle-control level.

PMID- 9652753
TI  - Reduction of tumour oxygenation during and after photodynamic therapy in vivo:
      effects of fluence rate.
AB  - It has been proposed that the generation of O2 during photodynamic therapy (PDT)
      may lead to photochemical depletion of ambient tumour oxygen, thus causing acute
      hypoxia and limiting treatment effectiveness. We have studied the effects of
      fluence rate on pO2, in the murine RIF tumour during and after PDT using 5 mg kg(
      1) Photofrin and fluence rates of 30, 75 or 150 mW cm(-2). Median pO2 before PDT
      ranged from 2.9 to 5.2 mmHg in three treatment groups. Within the first minute of
      illumination, median tumour pO2 decreased with all fluence rates to values
      between 0.7 and 1.1 mmHg. These effects were rapidly and completely reversible if
      illumination was interrupted. During prolonged illumination (20-50 J cm(-2)) pO2
      recovered at the 30 mW cm(-2) fluence rate to a median value of 7.4 mmHg, but
      remained low at the 150 mW cm(-2) fluence rate (median pO2 1.7 mmHg). Fluence
      rate effects were not found after PDT, and at both 30 and 150 mW cm(-2) median
      tumour pO2 fell from control levels to 1.0-1.8 mmHg within 1-3 h after treatment
      conclusion. PDT with 100 J cm(-2) at 30 mW cm(-2) caused significantly (P =
      0.0004) longer median tumour regrowth times than PDT at 150 mW cm(-2), indicating
      that lower fluence rate can improve PDT response. Vascular perfusion studies
      uncovered significant fluence rate-dependent differences in the responses of the
      normal and tumour vasculature. These data establish a direct relationship between
      tumour pO2, the fluence rate applied during PDT and treatment outcome. The
      findings are of immediate clinical relevance.

PMID- 9652754
TI  - Nitrogen mustard up-regulates Bcl-2 and GSH and increases NTP and PCr in HT-29
      colon cancer cells.
AB  - We hypothesized that unexplained increases in nucleoside triphosphates (NTP)
      observed by 31P magnetic resonance spectroscopy (MRS) after treatment of tumours
      by DNA-damaging agents were related to chemotherapy-induced up-regulation of the
      bcl-2 gene and DNA damage prevention and repair processes. To test this
      hypothesis, we treated HT-29 cells with 10(-4) M nitrogen mustard (HN2) and
      performed sequential perchloric acid extractions in replicate over 0-18 h. By
      reference to an internal standard (methylene diphosphonic acid), absolute changes
      in 31P-detectable high-energy phosphates in these extracts were determined and
      correlated with changes in bcl-2 protein levels, cell viability, cell cycle,
      apoptosis and total cellular glutathione (GSH) (an important defence against DNA
      damage from alkylating agents). After HN2 administration, bcl-2 protein levels in
      the HT-29 cell line rose at 2 h. Cell viability declined to 25% within 18 h, but
      apoptosis measured using fluorescence techniques remained in the 1-4% range.
      Increased cell division was noted at 4 h. Two high-energy interconvertible
      phosphates, NTP (P < or = 0.006) and phosphocreatine (PCr) (P < or = 0.0002),
      increased at 2 h concurrently with increased levels of bcl-2 protein and
      glutathione. This study demonstrates that bcl-2 and glutathione are up-regulated
      by HN2 and links this to a previously unexplained 31P MRS phenomenon: increased
      NTP after chemotherapy.

PMID- 9652755
TI  - Prolonged in vivo tumour retention of a human diabody targeting the extracellular
      domain of human HER2/neu.
AB  - Single-chain Fv (scFv) molecules exhibit highly specific tumour-targeting
      properties in tumour-bearing mice. However, because of their smaller size and
      monovalent binding, the quantities of radiolabelled scFv retained in tumours
      limit their therapeutic applications. Diabodies are dimeric antibody-based
      molecules composed of two non-covalently associated scFv that bind to antigen in
      a divalent manner. In vitro, diabodies produced from the anti-HER2/neu (c-erbB-2)
      scFv C6.5 displayed approximately 40-fold greater affinity for HER2/neu by
      surface plasmon resonance biosensor measurements and significantly prolonged
      association with antigen on the surface of SK-OV-3 cells (t1/2 cell surface
      retention of > 5 h vs 5 min) compared with C6.5 scFv. In SK-OV-3 tumour-bearing
      scid mice, radioiodinated C6.5 diabody displayed a highly favourable balance of
      quantitative tumour retention and specificity. By as early as 4 h after i.v.
      administration, significantly more diabody was retained in tumour (10 %ID g(-1))
      than in blood (6.7 %ID ml(-1)) or normal tissue (liver, 2.8 %ID g(-1); lung, 7.1
      %ID g(-1); kidney, 5.2 %ID g(-1)). Over the next 20 h, the quantity present in
      blood and most tissues dropped approximately tenfold, while the tumour retained
      6.5 %ID g(-1) or about two-thirds of its 4-h value. In contrast, the 24-h tumour
      retention of radioiodinated C6.5 scFv monomer was only 1 %ID g(-1). When diabody
      retentions were examined over the course of a 72-h study and cumulative area
      under the curve (AUC) values were determined, the resulting tumor-organ AUC
      ratios were found to be superior to those previously reported for other
      monovalent or divalent scFv molecules. In conclusion, the diabody format provides
      the C6.5 molecule with a distinct in vitro and in vivo targeting advantage and
      has promise as a delivery vehicle for therapeutic agents.

PMID- 9652756
TI  - Immune stimulatory potential of B7.1 and B7.2 retrovirally transduced melanoma
      cells: suppression by interleukin 10.
AB  - The immunostimulatory capacities of B7.1-and B7.2- expressing melanoma cells were
      investigated. A365, 960306 and 950504 melanomas, established from nodular
      melanoma lesions, were retrovirally transduced. Irradiated B7-, B7.1+ and B7.2+
      melanoma cells were co-cultured with autologous or allogeneic peripheral blood
      mononuclear cells (PBMCs). Proliferation was assessed by [3H]thymidine uptake.
      mRNA encoding for interleukin 2 (IL-2), IL-4, IL-10 and interferon gamma (IFN
      gamma) was determined. IFN-gamma, IL-2, IL-4 and IL-10 secretion were quantitated
      by ELISA. B7.1+ and B7.2+ melanomas induced proliferation of PBMCs and mRNA for
      IL-2 and IFN-gamma. After co-incubation of transduced melanoma cells with PBMCs,
      high levels of IL-10 were detectable in the supernatant. The presence of
      neutralizing anti-IL-10 antibodies resulted in enhanced proliferation and IL-2
      and IFN-gamma secretion. Our data indicate that B7.1- and B7.2-transduced
      melanoma cells trigger lymphocytic proliferation with transcription of IL-10, IL
      2 and IFN-gamma. Blocking of IL-10 augments these effects. Gene therapy protocols
      using tumour cells as a vaccine have to consider the adverse effects of IL-10.

PMID- 9652757
TI  - Hepatocyte growth factor-stimulated renal tubular mitogenesis: effects on
      expression of c-myc, c-fos, c-met, VEGF and the VHL tumour-suppressor and related
      genes.
AB  - Hepatocyte growth factor (HGF/SF) is a potent renal proximal tubular cell (PTEC)
      mitogen involved in renal development. HGF/SF is the functional ligand for the c
      met proto-oncogene, and germline c-met mutations are associated with familial
      papillary renal cell carcinoma. Somatic von Hippel-Lindau disease tumour
      suppressor gene (VHL) mutations are frequently detected in sporadic clear cell
      renal cell carcinomas (RCC), and germline VHL mutations are the commonest cause
      of familial clear cell RCC. pVHL binds to the positive regulatory components of
      the trimeric elongin (SIII) complex (elongins B and C) and has been observed to
      deregulate expression of the vascular endothelial growth factor (VEGF) gene.
      HGF/SF has similarly been reported to up-regulate expression of the VEGF gene in
      non-renal experimental systems. To investigate the mechanism of HGF/SF action in
      PTECs and, specifically, to examine potential interactions between the HGF/c-met
      and the VHL-mediated pathways for renal tubular growth control, we have isolated
      untransformed PTECs from normal kidneys, developed conditions for their culture
      in vitro and used these cells to investigate changes in mRNA levels of the VHL,
      elongin A, B and C, VEGF, c-myc, c-fos and c-met genes after HGF/SF exposure.
      Significant elevations in the mRNA levels of VEGF, c-myc, c-fos, c-met and
      elongins A, B and C, but not VHL, were detected after HGF/SF stimulation of human
      PTECs (P < 0.02), with a consistent order of peak levels observed over successive
      replicates (c-fos at 1 h, VEGF at 2-4 h, c-myc, at 4 h, followed by c-met and all
      three elongin subunits at 8 h). This study highlights the spectrum of changes in
      gene expression observed in PTECs after HGF/SF stimulation and has identified
      possible candidate mediators of the HGF/SF-induced mitogenic response. Our
      evidence would suggest that the changes in PTEC VEGF expression induced by HGF/SF
      are mediated by a VHL-independent pathway.

PMID- 9652758
TI  - Wt-p53 action in human leukaemia cell lines corresponding to different stages of
      differentiation.
AB  - Recent studies support the potential application of the wt-p53 gene in cancer
      therapy. Expression of exogenous wt-p53 suppresses a variety of leukaemia
      phenotypes by acting on cell survival, proliferation and/or differentiation. As
      for tumour gene therapy, the final fate of the neoplastic cells is one of the
      most relevant points. We examined the effects of exogenous wt-p53 gene expression
      in several leukaemia cell lines to identify p53-responsive leukaemia. The
      temperature-sensitive p53Val135 mutant or the human wt-p53 cDNA was transduced in
      leukaemia cell lines representative of different acute leukaemia FAB subtypes,
      including M1 (KG1), M2 (HL-60), M3 (NB4), M5 (U937) and M6 (HEL 92.1.7), as well
      as blast crisis of chronic myelogenous leukaemia (BC-CML: K562, BV173) showing
      diverse differentiation features. By morphological, molecular and biochemical
      analyses, we have shown that exogenous wt-p53 gene expression induces apoptosis
      only in cells corresponding to M1, M2 and M3 of the FAB classification and in BC
      CML showing morphological and cytochemical features of undifferentiated blast
      cells. In contrast, it promotes differentiation in the others. Interestingly,
      cell responsiveness was independent of the vector used and the status of the
      endogenous p53 gene.

PMID- 9652759
TI  - Loss of heterozygosity at chromosome 9p in ductal carcinoma in situ and invasive
      carcinoma of the breast.
AB  - Twenty-three cases of ductal carcinoma in situ (DCIS), ten of which had an
      associated invasive component, were studied for loss of heterozygosity (LOH) of
      microsatellite markers on chromosome 9p and the results compared with a panel of
      20 invasive breast carcinomas. In addition to the gene encoding p16, chromosome
      9p is also thought to contain other putative tumour-suppressor genes. If the
      three panels of breast tumours showed LOH of markers in this region this would
      suggest that such putative genes were important in breast carcinogenesis. By
      studying both preinvasive and invasive breast tumours, it should also be possible
      to gain further information about the relationship between lesions of a different
      stage and to determine whether DCIS is indeed a precursor of invasive ductal
      carcinoma. Levels of LOH were low in the invasive-only set of tumours.
      Surprisingly, considerably higher levels of loss were observed in the tumours
      with an in situ component. Also, much heterogeneity was observed between
      different DCIS ducts or invasive tumour and DCIS from the same case.

PMID- 9652760
TI  - SupraMolecular BioVectors (SMBV) improve antisense inhibition of erbB-2
      expression.
AB  - New therapeutic strategies are now being developed against adenocarcinoma
      associated with erbB-2 amplification, particularly by inhibiting p185erbB-2
      expression. Antisense oligodeoxynucleotides seem promising for this purpose as
      long as they are efficiently protected against degradation and targeted into the
      cells. We present antisense oligonucleotide carriers, the supramolecular
      biovectors (SMBVs), for which we have already demonstrated the ability to improve
      both cellular uptake and protection of oligodeoxynucleotide. The present work
      demonstrates that SMBVs elicit a specific and non-toxic action of antisense
      compounds in a cell model, irrespective of their sensitivity to nucleases. This
      is a major point, considering the specificity problems associated with the use of
      nuclease-resistant phosphorothioate oligodeoxynucleotide. SMBVs improve antisense
      efficiency of oligodeoxynucleotide designed against p185erbB-2, with a complete
      growth arrest of SK-Br-3, human adenocarcinoma mammary cells that overexpress
      p185erbB-2 and no effect on MCF-7 cells that normally express p185erbB-2. The
      comparison of SMBVs with DOTAP reveals the statistically higher efficiency of
      SMBVs, which allows the antisense inhibition of p185erbB-2 expression in 65-75%
      of SK-Br-3 cells (P < 0.05). The efficiency and controlled synthesis of SMBVs
      underline their potentialities as oligodeoxynucleotide carriers for in vivo
      experiments.

PMID- 9652761
TI  - Down-regulation of Fas gene expression in colon cancer is not a result of allelic
      loss or gene rearrangement.
AB  - Expression of Fas, an apoptosis-inducing receptor, in colonic epithelium is
      progressively reduced during malignant transformation. We have examined the human
      Fas gene for loss of heterozygosity (LOH) and gross rearrangements in colon
      tumours and matched normal mucosa. Polymerase chain reaction (PCR) primers were
      designed to span a DraI restriction fragment length polymorphic site in the gene.
      Heterozygosity was detected in normal DNA samples by PCR amplification of the
      polymorphic site and restriction enzyme digestion. Thirty-eight of 88 patients
      (43%) with colon carcinomas were informative for the assay, and LOH was detected
      in 6 of the 38 (16%) corresponding tumours. Tumours from three patients with LOH
      did not express detectable Fas mRNA, and Fas expression was reduced or absent in
      7 of 11 tumours from informative patients without LOH. Southern blotting of
      tumour DNA samples was used to detect rearrangement of the Fas gene, but no
      altered hybridization patterns were observed in 64 tumours analysed. These
      findings indicate that disruption of the Fas gene is not primarily responsible
      for the loss of Fas protein expression reported in colon cancer. We have also
      shown that loss of Fas gene transcription is common in these tumours, which may
      be due to epigenetic gene silencing.

PMID- 9652762
TI  - Frequent alterations of cell cycle regulators in early-stage breast lesions as
      detected by immunohistochemistry.
AB  - Progression through G1 phase of the eukaryotic cell cycle is tightly controlled
      by cyclin-dependent kinases (CDK). These proteins form part of a regulatory
      pathway including the cyclin-dependent kinase inhibitor (CKI) p16, D-type cyclins
      and the product of the retinoblastoma gene pRb. Aberration of any one of these
      components may lead to uncontrolled proliferation contributing to neoplasia.
      Three of these proteins, cyclin D1, pRb and p16, were analysed by
      immunohistochemistry on archival paraffin sections to determine whether
      expression patterns were different in preinvasive ductal carcinoma in situ (DCIS)
      and invasive breast tumours relative to normal. Genetic analysis of the gene
      encoding cyclin D1 (CCND1) was also carried out, using an intragenic restriction
      fragment-length polymorphism (RFLP) to assess possible allelic imbalance. A
      majority of the tumours studied (approximately 90%) showed abnormalities in
      expression of at least one of these proteins. Overexpression of cyclin D1 was
      found in approximately 49% cases, reduced expression of p16 in approximately 46%
      and reduced expression of pRb in approximately 37%. Allelic imbalance of cyclin
      D1 was found in approximately 57% cases.

PMID- 9652763
TI  - Immunohistochemical detection of DNA topoisomerase IIalpha, P-glycoprotein and
      multidrug resistance protein (MRP) in small-cell and non-small-cell lung cancer.
AB  - Non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) differ
      significantly in their clinical response to topoisomerase IIalpha (topo-IIalpha)
      directed drugs, such as etoposide and teniposide, as NSCLC is virtually
      insensitive to single-agent therapy, while SCLC responds in two-thirds of cases.
      Preclinical studies have indicated that resistance to topo-IIalpha drugs depends
      on topo-IIalpha content and/or activity, the altered-topo-II multidrug resistance
      phenotype (at-MDR) and/or one of two different drug efflux pumps, P-glycoprotein
      (P-gp) and the multidrug resistance protein (MRP). Immunohistochemical analysis
      on paraffin-embedded tissue from 27 cases of untreated NSCLC and 29 cases of
      untreated SCLC (of which additional tumour biopsies after treatment with topo
      IIalpha-directed drugs were available in ten cases) yielded the following
      results: NSCLC had significantly less topo-IIalpha than SCLC (P < 0.0001), as
      only 5 out of 27 NSCLC cases had > 5% positive cells compared with 28 out of 29
      SCLC, and 0 out of 27 NSCLC had > 25% positive cells compared with 26 out of 29
      SCLC. P-gp was detected in > 5% of cells in only 3 out of 27 NSCLC and in 6 out
      of 29 SCLC, and MRP in 5 out of 27 of NSCLC and 9 out of 29 SCLC. After treatment
      of patients with SCLC with either etoposide or teniposide, which are topo-IIalpha
      directed drugs, there was an increase in MRP (P < 0.1) and P-gp (P < 0.05)
      positivity, while topo-IIalpha decreased (P < 0.05). In conclusion, the major
      difference between untreated NSCLC and SCLC was in topo-IIalpha content. In the
      small series of ten patients treated for SCLC, all three MDR phenotypes appeared
      to increase.

PMID- 9652764
TI  - Randomized trial comparing protracted infusion of 5-fluorouracil with weekly
      doxorubicin and cyclophosphamide with a monthly bolus FAC regimen in metastatic
      breast carcinoma (SPM90).
AB  - Infusional 5-fluorouracil in advanced breast cancer has been associated with
      improved clinical response rates when compared with conventional bolus therapy.
      As a first line of chemotherapy in proven metastatic breast carcinoma, 258 women
      were randomly assigned to receive FAC consisting of 5-fluorouracil (F) 600 mg m(
      2) intravenously (i.v.) over 1 h on days 1, 2 and 3, doxorubicin (A) 50 mg m(-2)
      i.v. bolus on day 1 and cyclophosphamide (C), 400 mg m(-2) i.v. bolus on days 1,
      2 and 3 or 'FULON' consisting of 5-fluorouracil 250 mg m(-2) day(-1) continuously
      infused from day 1 to day 22, doxorubicin 15 mg m(-2) i.v. bolus on days 1, 8, 15
      and 22 and cyclophosphamide 300 mg m(-2) i.v. bolus on days 1, 8, 15 and 22.
      Chemotherapy courses were administered 4-weekly for the bolus regimen and 6
      weekly for FULON. Pretreatment characteristics were identical between the two
      groups. Response rates were 54% in the FAC arm and 53% in the FULON arm. Time to
      progression was 14 months in the FAC arm and 12 months in the FULON arm.
      Differences were not statistically significant. Median overall survival duration
      for all patients was 22 months. Haematological toxicity was more severe in the
      bolus-treated group (P = 0.05), as were nausea and vomiting (P < or = 0.01). We
      conclude that the two regimens appeared equally effective but have different
      toxicities.

PMID- 9652765
TI  - Bolus/infusional 5-fluorouracil and folinic acid. A report on two prospective,
      consecutive phase II studies with 5-fluorouracil dose escalation.
AB  - We have used a relatively new trial methodology, the group sequential design, to
      prospectively evaluate two dose levels of bolus/infusional 5-fluorouracil (5-FU)
      and folinic acid in 192 consecutive-patients with advanced colorectal carcinoma.
      On day 1, all patients received 200 mg m(-2) of folinic acid infusion over 2 h.
      Cohort A (n = 102 patients) received 500 mg m(-2) 5-FU by i.v. 15-min infusion
      followed by an infusion of 500 mg m(-2) 5-FU over 22 h. Treatment was repeated on
      day 2 and further cycles given 2-weekly. After sequential analysis excluded a
      response rate of over 40%, cohort B (n = 90 patients) received an increased dose
      of 600 mg m(-2) 5-FU bolus and infusion. Patients had received no prior 5-FU
      therapy and the two cohorts had similar demographic features. In 179 evaluable
      patients, the overall response rate was 18% (95% CI 12-24%) with CR of 6% and PR
      of 12%, with no difference between the two cohorts. Overall median survival was
      34 weeks (95% CI 30-39) with no significant difference between cohorts (median
      survival 32 and 37 weeks in cohort A and B respectively; P = 0.27). On
      multivariate analysis, poor performance status, elevated initial WBC and alkaline
      phosphatase and low serum albumin were associated with reduced survival (P <
      0.05), and initial raised WBC showed an association with reduced likelihood of
      response (P = 0.002). Overall toxicity was low with CTC grade 3 mucositis,
      diarrhoea, nausea or vomiting in < or = 6% of patients and no treatment-related
      deaths. Significant (grade 3 or above) leucopenia was more common in cohort B
      than in cohort A (9% and 1% respectively); there were more dose reductions, and
      the median administered dose intensity was lower in cohort B than in cohort A
      (89% and 97% respectively; P = 0.006). In this group of relatively unselected
      patients, we have confirmed a relatively low objective response rate and median
      survival of 7.8 months with this regimen. There was no significant difference in
      outcome between the two dose levels but the higher dose of 5-FU was associated
      with more dose reductions and greater toxicity.

PMID- 9652766
TI  - Initial high anti-emetic efficacy of granisetron with dexamethasone is not
      maintained over repeated cycles.
AB  - We have reported previously that the anti-emetic efficacy of single agent 5HT3
      antagonists is not maintained when analysed with the measurement of cumulative
      probabilities. Presently, the most effective anti-emetic regimen is a combination
      of a 5HT3 antagonist plus dexamethasone. We, therefore, assessed the sustainment
      of efficacy of such a combination in 125 patients, scheduled to receive cisplatin
      > or = 70 mg m(-2) either alone or in combination with other cytotoxic drugs.
      Anti-emetic therapy was initiated with 10 mg of dexamethasone and 3 mg of
      granisetron intravenously, before cisplatin. On days 1-6, patients received 8 mg
      of dexamethasone and 1 mg of granisetron twice daily by oral administration.
      Protection was assessed during all cycles and calculated based on cumulative
      probability analyses using the method of Kaplan-Meier and a model for
      transitional probabilities. Irrespective of the type of analysis used, the anti
      emetic efficacy of granisetron/dexamethasone decreased over cycles. The initial
      complete acute emesis protection rate of 66% decreased to 30% according to the
      method of Kaplan-Meier and to 39% using the model for transitional probabilities.
      For delayed emesis, the initial complete protection rate of 52% decreased to 21%
      (Kaplan-Meier) and to 43% (transitional probabilities). In addition, we observed
      that protection failure in the delayed emesis period adversely influenced the
      acute emesis protection in the next cycle. We conclude that the anti-emetic
      efficacy of a 5HT3 antagonist plus dexamethasone is not maintained over multiple
      cycles of highly emetogenic chemotherapy, and that the acute emesis protection is
      adversely influenced by protection failure in the delayed emesis phase.

PMID- 9652767
TI  - Elevated plasma levels of transforming growth factor (TGF)-beta1 and TGF-beta2 in
      patients with disseminated malignant melanoma.
AB  - Overexpression of transforming growth factor-beta isoforms (TGF-beta1, -beta2, 
      beta3) has been previously reported in human melanoma cell lines and tumours. The
      aim of the present study was to evaluate the plasma levels of TGF-beta isoforms
      in melanoma patients. Significantly elevated levels of TGF-beta1 (4.2 x the
      controls, P = 0.0094) and of TGF-beta2 (1.5 x the controls, P = 0.012) but not of
      TGF-beta3 were measured in patients with disseminated but not locoregional
      melanoma. These results indicate systemic circulation of potentially
      immunosuppressive peptides of the TGF-beta family in end-stage melanoma patients.

PMID- 9652768
TI  - Prognostic value of urokinase plasminogen activator in primary breast carcinoma:
      comparison of two immunoassay methods.
AB  - Urokinase-type plasminogen activator (uPA) is a potentially important prognostic
      factor in breast cancer for identifying patients at high risk of recurrence. This
      retrospective study assessed two enzyme-linked immunosorbent assay (ELISA)
      methods measuring uPA antigen levels in 499 primary breast cancer cytosols. Both
      uPA methods were applied to cytosols used routinely for oestrogen (ER) and
      progesterone (PgR) receptor assays. uPA was determined using a classical ELISA
      method (Imubind; American Diagnostica) and a novel automatic immunoluminometric
      assay (Lia; Sangtec Medical). The uPA Imubind method revealed about twice as much
      uPA antigen (median 0.75 ng mg(-1) protein) as the uPA Lia method (median 0.38 ng
      mg(-1) protein). The correlation coefficient between the two methods was
      acceptable (r = 0.81), but the two techniques are not interchangeable. Univariate
      analyses confirmed the poor outcome of patients whose tumours contained large
      amounts of uPA, regardless of the technique used. Multivariate analyses showed
      that uPA Imubind and uPA Lia values were both strong independent prognostic
      factors.

PMID- 9652769
TI  - Cell proliferation measured by MIB1 and timing of surgery for breast cancer.
AB  - We have investigated the use of the antibody MIB1 as a proliferative and
      prognostic marker in breast cancer and whether changes in proliferative activity
      could account for differences in prognosis of premenopausal women operated on
      during different phases of the menstrual cycle. MIB1 expression was strongly
      correlated with S-phase fraction and histological grade. There was no difference
      in MIB1 scores between different phases of the menstrual cycle. Both MIB1 score
      and timing of surgery correlated significantly with duration of survival, while
      the two together were even stronger predictors of overall survival. Women with
      slowly proliferating tumours surgically removed in the luteal phase had a very
      good prognosis, whereas women with rapidly proliferating tumours excised at other
      times of the cycle had a worse prognosis.

PMID- 9652770
TI  - Hypertension, obesity and their medications in relation to renal cell carcinoma.
AB  - A population-based, case-control study was conducted in Los Angeles County,
      California, to investigate the inter-relationships of obesity, hypertension and
      medications in relation to renal cell carcinoma (RCC) risk. A total of 1204 RCC
      patients and an equal number of neighbourhood controls were included. Obesity was
      a strong risk factor for RCC. A fourfold increase in risk was observed for those
      with usual body mass index (kg m(-2)) of > or = 30 vs < 22. A history of
      hypertension was another strong, independent risk factor for RCC [odds ratio (OR)
      = 2.2; 95% confidence interval (CI) = 1.8, 2.6]. There was little evidence that
      use of diuretics was directly related to RCC development. Use of diuretics for
      reasons other than hypertension (primarily for weight control) was unrelated to
      risk among self-reported normotensive subjects (OR = 1.2; 95% CI = 0.7, 2.2).
      Among hypertensive subjects, heavy users of diuretics experienced similar risk as
      light users (OR = 0.9 among subjects with lifetime dose of > or = 137 g compared
      with those with lifetime dose of < 43 g). Similarly, normotensive subjects who
      took non-diuretic antihypertensives regularly showed no increased risk for RCC
      (OR = 1.1; 95% CI = 0.6-1.8), and intake among hypertensive subjects did not
      further increase their risk. Regular use of amphetamine-containing diet pills was
      associated with a twofold increase in RCC risk (95% CI = 1.4-2.8) and the risk
      increased with increasing dose of amphetamines. However, the fraction of cases
      possibly related to this exposure is small (population-attributable risk = 5%).

PMID- 9652771
TI  - Survival analysis of 5595 head and neck cancers--results of conventional
      treatment in a high-risk population.
AB  - This is a study of 5595 head and neck cancer patients treated during 1987-89 at
      TMH, Mumbai. The study included 1970 oral cancers (ICD 140-145), 1495
      oropharyngeal cancers (ICD 1410, 1453, 146), 1255 hypopharyngeal cancers (ICD
      148), 125 nasopharyngeal cancers (ICD 147) and 750 laryngeal cancers (ICD 161).
      The clinical extent of disease at presentation was based on TNM group staging
      (UICC 1978). For the majority of sites, patients attended the hospital during
      stage III and stage IV of the disease; the only exception was for cancers of the
      lower lip, anterior tongue and vocal cord when between 46.2% and 56.5% of
      patients with localized cancer (stage I and II) were seen. Generally, surgery
      either alone or with radiation has been administered for oral cancer patients
      whereas radiation either alone or in combination with chemotherapy was
      administered for other head and neck sites. The overall 5-year survival rate was
      in the range of 20-43% for oral cancer, 8-25% for pharyngeal cancers and 25-62%
      for laryngeal cancer. The 5-year relative survival rates were more or less in
      agreement with the results published by the Eurocare study for head and neck
      cancers. The importance of primary prevention in head and neck cancer is
      stressed.

PMID- 9652772
TI  - Breast cancer in Norway 1970-1993: a population-based study on incidence,
      mortality and survival.
AB  - The incidence, mortality and survival of breast cancer patients from 1970 to 1993
      were studied using data from the Cancer Registry of Norway. The age-adjusted
      incidence rate increased from 62.0 to 76.9 per 100,000 person-years during the
      period, and more than 2000 cases are now registered annually. The increase tends
      to be highest in the age group below 40 years. The increase is mainly found in
      cases with localized tumours at the time of diagnosis. The mortality rate has
      been almost unchanged in the period; the age adjusted mortality rate is 27.0 per
      100,000 person-years at the end of the study period. The 5-year overall survival
      has increased among cases with axillary lymph node metastases at the time of
      diagnosis; the other stages show only little improvement.

PMID- 9652773
TI  - The effects of interaction between familial and reproductive factors on breast
      cancer risk: a combined analysis of seven case-control studies.
AB  - In this paper, a combined analysis was performed to study the interaction between
      familial risk and reproductive life factors. In particular, the interaction
      between familial risk and breast cell mitotic activity (BCMA), as assessed by
      duration of ovarian activity, was investigated because of the potential
      importance of mitotic activity on genetically susceptible cells. The present
      analysis included 3152 cases and 4404 controls in seven case-control studies from
      four countries. The interaction effect was estimated in each study separately,
      then combined using two different methods: a multivariate weighted average and a
      Bayesian random-effects model. The main effects of reproductive life factors on
      the risk of breast cancer were in agreement with the previous findings. In
      particular, an increased duration of BCMA before the first childbirth and over
      life was found to increase the risk of breast cancer (P < 0.001). Slightly
      increasing but non-significant, familial risks were observed with increasing
      number of children (P = 0.17), increasing age at first childbirth (P > 0.2) and
      increasing duration of BCMA (P > 0.2). There was no modification in familial risk
      with age at menarche and no clear pattern with menopause characteristics. A weak
      influence of reproductive and menstrual factors on the familial risk emerged from
      the present study.

PMID- 9652775
TI  - From Mendel to the millennium: the genome project.

PMID- 9652774
TI  - Segregation analysis of epithelial ovarian cancer in Finland.
AB  - Epithelial ovarian cancer is known to aggregate in families. The dominantly
      inherited ovarian cancer predisposing genes, BRCA1, BRCA2 and genes involved in
      the hereditary non-polyposis colorectal cancer (HNPCC) syndrome, have recently
      been identified. However, in the majority of families with more than one case of
      ovarian cancer, dominant inheritance cannot be recognized. We investigated
      familial clustering of epithelial ovarian cancer in a population-based sample of
      663 Finnish ovarian cancer patients. A segregation analysis with the POINTER
      software was conducted on the 937 nuclear families from these 663 pedigrees. The
      major gene model was favoured, and the sporadic and multifactorial models were
      strongly rejected. In the studied population, the best fitting model was a
      recessive mode of inheritance, and 8% of ovarian cancer patients were estimated
      to be homozygous for the deleterious genotype. This evidence for recessively
      inherited ovarian cancer predisposition should be interpreted cautiously, as the
      analysis is subject to certain errors, which are discussed in the article.
      Results of this analysis, however, strongly emphasize the role of genetic factors
      in all familial aggregation of epithelial ovarian cancer.

PMID- 9652776
TI  - Do neurological disorders in childhood pose a risk for mental health in young
      adulthood?
AB  - To assess whether juvenile-onset epilepsy or motor disability is complicated by
      an increased number of mental health disorders or experience of psychosomatic
      symptoms in young adulthood, we studied 81 subjects with epilepsy and 52 with
      motor disabilities at the age of 19 to 25 years and compared them with 211
      controls. The main diagnostic tool, the Present State Examination, was
      administered to those attending the interviews in person who were of normal
      intelligence; there were 62, 38, and 123 subjects in the three categories,
      respectively. Compared with the controls, the subjects with epilepsy showed an
      equal prevalence of psychiatric disorders whereas those with motor disabilities
      had a significantly higher prevalence, particularly of depressive disorders. The
      reported prevalence of psychosomatic symptoms confirmed this main result.
      Psychological illness affected everyday life of two out of five subjects with
      motor disabilities, but only half of those in the other two groups. It is
      concluded that motor disability since childhood, but not epilepsy, could be a
      factor that increases susceptibility to psychiatric morbidity, especially
      depression, and causes a large number of psychosomatic symptoms. The results
      challenge staff of clinics working with such adolescents to find individual
      approaches in preventing the negative influence of psychological disorders on
      social life.

PMID- 9652777
TI  - Life expectancy of adults with cerebral palsy.
AB  - To determine the predictors of mortality and find the life expectancies of adults
      with cerebral palsy (CP), data on 24,768 individuals aged 15 years and over who
      received services in California between January 1980 and December 1995 were
      analyzed. Multivariate statistical methods to identify mortality predictors, and
      actuarial methods to determine corresponding life expectancies were used. The key
      predictors were lack of basic functional skills: mobility and feeding. Adults
      lacking these skills had much reduced life expectancies, as short as 11 years for
      the worst functioning groups. By contrast, survival of high-functioning adults
      was close to that of the general population. The influence on survival of
      cognitive skills, type of CP, and other factors appears to be expressed largely
      through their effect on basic functioning. Life expectancies of adults of a given
      age can differ by 40 years or more, according to their functional level.

PMID- 9652778
TI  - Survival in cerebral palsy: the role of severity and diagnostic labels.
AB  - The aim of this study was to review survival and certified causes of death of 584
      children on a population-based register of cerebral palsy (CP), and to assess the
      impact on these of an additional diagnostic label. The register, established in
      1985, comprised children with CP born from 1980 to about 1987 who were resident
      at the time of notification in the south-east of England in a region with between
      3 and 4 million population, defined by the boundaries of the regional health
      authority (North East Thames Regional Health Authority). The current report
      concerns deaths of residents born between 1980 and 1986, who had been registered
      but had later died, as well as of eligible children who had not been registered
      while alive but whose cause of death was CP. These were identified at the Office
      of Population Censuses and Surveys who also supplied copies of death certificates
      for this study. For children notified while alive, information about motor
      severity and other diagnostic labels was sought at entry to the register and
      again between 3.5 and 4 years and between 7 and 8 years. For this study, children
      known to have a postneonatal onset, a progressive or non-cerebral cause of motor
      signs, or minimal motor involvement were excluded. Thirty-nine of 584 children
      included in this study had died by the end of 1995. No deaths had occurred in
      children known to have less than four-limb involvement. Survival of the group
      known to have an additional diagnostic label was significantly lower (86.2%) than
      that of the group with no known label (96.3%; P=0.01), and remained lower,
      although not significantly, if only those with severe four-limb involvement were
      compared (75.3% versus 92.4%; P=0.2). The greater severity of limb involvement in
      those with an additional diagnosis may not account for this difference. Of the 37
      children with death certificates available, CP was mentioned as a cause in only
      24.

PMID- 9652779
TI  - Speech and language development of children born at < or = 32 weeks' gestation: a
      5-year prospective follow-up study.
AB  - Speech and language comprehension and production were assessed at the age of 5
      years in a cohort of children born preterm at < or = 32 weeks' gestational age
      (N=55) in comparison with children born at term and of similar age, sex, and
      social backgrounds. Data both including and excluding major neurological
      disabilities are presented. Mean performance for the entire group of preterm
      children was significantly lower than for the controls on most of the measures
      including the composite IQ scores. When the nine children who had major
      neurological disabilities were excluded from the preterm group, statistically
      significant differences were found on four of the total 12 speech and language
      measures. Intellectually normal preterm children without major neurological
      disability were slower than the controls on rapid word retrieval. In addition,
      difficulties in comprehending relative concepts were typical for the preterm
      children. The results suggest 'subtle dysnomia', which is indicative of later
      reading problems. On global verbal measures and on the basic speech and language
      aspects the study groups did not differ. Specific language impairment, defined as
      a discrepancy of > 1SD between Performance IQ and Verbal IQ scores, showed a
      tendency to be more common in the control group. Within both the study groups,
      the boys showed a tendency for a greater discrepancy between their Performance
      and Verbal IQ scores.

PMID- 9652780
TI  - A dyspraxic deficit in specific language impairment and developmental
      coordination disorder? Evidence from hand and arm movements.
AB  - The extent to which children with either specific language impairment (SLI) or
      developmental coordination disorder (DCD) could be considered dyspraxic was
      examined using three tasks involving either familiar, or unfamiliar actions. SLI
      is diagnosed in children who fail to develop language in the normal fashion for
      no apparent reason, while the DCD diagnosis is applied to a child who experiences
      problems with movement in the absence of other difficulties. Seventy-two children
      aged between 5 and 13 years participated, falling into one of four groups: (1)
      children with specific language impairment (SLI), (2) children with developmental
      coordination disorder (DCD), (3) age-matched control children, and (4) younger
      control children. The performance of the clinical groups resembled that of
      younger normally developing children. Children with SLI, DCD, and the younger
      controls showed significant difficulty on the task requiring the production of
      familiar, but not unfamiliar postures. The deficit observed in the SLI group is
      particularly striking because it was seen both in those with and those without
      recognized motor difficulties.

PMID- 9652781
TI  - Interlimb coupling in children with hemiplegic cerebral palsy during reaching and
      grasping at speed.
AB  - This investigation examined reaching and grasping at speed in children with
      hemiplegic cerebral palsy. Of particular interest was the effect of the movement
      of the less affected limb on the more affected one. Using 3D kinematic analysis
      and standard video recordings, 11 children with hemiplegia of varying degrees of
      severity were examined performing three reaching tasks at speed. The data were
      analysed and the extent and nature of the interlimb coupling occurring in each
      child were assessed using a number of different variables. The results are
      discussed in terms of spatial, temporal, and postural coupling. All children
      coupled to some degree but differed in the degree and type of coupling. Speed
      facilitated coupling which was stronger during the first part of the movement in
      all three tasks. The variables affecting coupling included the type of coupling,
      the nature of the task, the importance of context, and the stage in the movement.

PMID- 9652782
TI  - The predictive value of developmental testing of extremely jaundiced African
      infants.
AB  - The predictive value of the Neonatal Neurological Examination (NNE) adapted from
      Prechtl (1977) and the Infant Motor Screen (IMS) from Nickel (1989) at 4 months
      was studied in severely jaundiced infants in Zimbabwe. Fifty infants were
      examined with the NNE, 41 with the IMS and 43 with the Bayley Scales of Infant
      Development (BSID) (Bayley 1969). Five infants had choreoathetosis and six had a
      motor delay at age 1 year. The NNE and IMS proved to be sensitive instruments
      particularly when two infants who became malnourished after the neonatal period
      were excluded. Logistic regression was used to investigate the relation between
      the BSID and five selected predictors from the NNE. This resulted in a correct
      classification of 93%. By using only the predictors acoustic blink and traction
      response, 80% of the infants were correctly classified but the number of false
      negatives was reduced from three to one.

PMID- 9652783
TI  - Turkish children's performance on Denver II: effect of sex and mother's
      education.
AB  - One thousand and ninety-one healthy Turkish children were tested with the Denver
      II developmental screening test and the data were analysed for sex and
      sociocultural differences. Few and inconsistent differences were observed between
      boys and girls. On the other hand, there were marked differences between
      sociocultural groups, particularly in terms of fine motor and language areas and
      in older preschool children. The effect of maternal education on the child's
      development is more important in countries where preschool education is not
      commonly available. Whether this effect diminishes after 1 or 2 years of
      schooling is to be investigated.

PMID- 9652784
TI  - Evolution of a form of pure alexia without agraphia in a child sustaining
      occipital lobe infarction at 2 1/2 years.
AB  - The progress of cognitive visual dysfunction over an 8-year period of a child who
      sustained bilateral occipital-lobe infarctions at the age of 2 1/2 years is
      described. She survived with normal intelligence and went on to attend mainstream
      school. She manifested many features of cognitive visual impairment and, in
      particular, developed a form of pure alexia without agraphia. She achieved some
      letter-by-letter reading but no sight vocabulary development, including to her
      own name. She learned to write imaginatively employing phonetically true spelling
      but cannot read what she has written. Her progress and the difficulties
      encountered during the management of her condition are discussed in this first
      case report of the evolution of pure alexia without agraphia in childhood. The
      features of this syndrome in the developing child who has never developed the
      capacity to read are contrasted with that seen in affected adults.

PMID- 9652785
TI  - Bilateral oedema of the basal ganglia in an echovirus type 21 infection: complete
      clinical and radiological normalization.
AB  - A 4-year-old girl with bilateral striatal oedema in association with an echovirus
      type 21 infection is reported. In the course of a prolonged upper respiratory
      tract infection, the patient developed muscular hypotonia, resting tremor,
      ataxia, sleepiness, hyperaesthesia, and indistinct speech. T2-weighted cranial
      MRI revealed bilateral oedema of the basal ganglia and the cerebellar peduncles.
      At follow-up after 3 months MRI changes and clinical symptoms had fully resolved.

PMID- 9652786
TI  - Juvenile familial amyotrophic lateral sclerosis: four cases with long survival.
AB  - Four cases are reported of juvenile familial amyotrophic lateral sclerosis
      (JFALS) with exceptionally long survival (mean=27 years), and consequent
      development of dementia. Subjects' mean age at onset was 15.7 years. Their
      clinical features and electrophysiological findings support the diagnosis. One
      subject's MRI scan showed severe atrophy to the cortex and brain stem; wallerian
      degeneration in the pyramidal pathway, as reported in other studies, could not be
      found. JFALS is characterized by the involvement of other neuronal systems not
      present in the adult form and by long survival after disease onset.

PMID- 9652787
TI  - Changes in liver fatty acid-binding protein in rat enzyme-altered foci.
AB  - The level of liver fatty acid-binding protein (L-FABP) was analyzed in enzyme
      altered foci (EAF) positive for GST-P, or after classification of foci into
      different subclasses by haematoxylin and eosin staining. Rats were treated with
      either an initiating single dose of diethylnitrosamine (DEN) followed by no
      treatment, treatment with phenobarbital, PCB, nafenopin or repeated injections of
      DEN, or alternatively non-treated or treated with nafenopin alone. Changes in the
      level of L-FABP were detected in the majority of EAF and both L-FABP-positive and
      -negative foci were seen. However, in rats initiated with DEN, EAF were almost
      exclusively L-FABP-negative. The fraction of L-FABP-negative foci increased with
      increasing foci size, while the time of treatment or the dose of the promoter did
      not seem to have any effect. It was also found that treatment with DEN gave a
      higher fraction of L-FABP-negative foci as compared to treatment with
      phenobarbital or PCB, indicating a specific effect of DEN. These data together
      with previously published findings suggest that L-FABP expression in EAF is
      determined by the initiating carcinogenic regimen and that it might be possible
      to use the expression of L-FABP in tumours to differentiate initiating chemicals.

PMID- 9652788
TI  - Caspase proteases mediate apoptosis induced by anticancer agent preactivated
      MC540 in human tumor cell lines.
AB  - The molecular events involved in tumor cell death induced by novel photoproducts
      of merocyanine 540 (pMC540) are poorly understood. Using HL60 leukemia and M14
      melanoma cell lines we investigated the role of the apoptotic pathway in pMC540
      mediated cell death. Tumor cells exposed to pMC540 showed cell size shrinkage and
      an increase in the sub-diploid DNA content. A loss of membrane phospholipid
      asymmetry associated with apoptosis was induced by pMC540 in both tumor cell
      lines as evidenced by the externalization of phosphatidylserine. A dose-dependent
      increase in caspase-3 protease activity suppressed by the tetrapeptide inhibitor
      DEVD-CHO was observed in both cell lines. Western blot analysis of poly (ADP
      ribose) polymerase, a caspase substrate, showed the classical cleavage pattern
      (116 to 89 kDa) associated with apoptosis in pMC540-treated cell lysates.
      Furthermore, caspase inhibition blocked the externalization of membrane PS,
      indicating that the loss of membrane phospholipid asymmetry is a downstream event
      of caspase activation. These findings demonstrate that tumor cell death induced
      by pMC540 is mediated by caspase proteases.

PMID- 9652789
TI  - Distant metastasis of gastric cancer is associated with elevated expression of
      the antimetastatic nm23 gene.
AB  - To understand the clinical significance of nm23 gene expression in gastric cancer
      patients, the Nm23-H1 protein level of fresh resected specimens from a total of
      37 gastric cancer patients was measured by Western blot analysis. The elevated
      nm23 expression group (Nm23-H1 protein level in tumor tissue greater than the
      75th percentile value of patients) was significantly associated with the
      histologically differentiated type (P = 0.036). This group had a higher incidence
      of distant (hematogeneous) metastasis (P = 0.0023) and a lower 2-year disease
      free survival rate (P = 0.033) than the non-elevated group. The result was not
      consistent with the previous assumption that nm23 is an antimetastatic gene for
      gastric cancer.

PMID- 9652790
TI  - Glutathione S-transferase-placental form expression and proliferation of
      hepatocytes in fumonisin B1-treated male and female Sprague-Dawley rats.
AB  - Fumonisin B1 (FB1), a mycotoxin produced by a common corn contaminant Fusarium
      moniliforme and a hepatocarcinogen in rats, has been previously suggested to act
      as a poor initiator, but a better promoter of gamma-glutamyltranspeptidase (GGT)
      positive rat liver preneoplastic lesions. Using glutathione S-transferase
      placental form (GSTP) as a more sensitive marker of initiation, we have further
      evaluated the initiating capacity of various doses of purified FB1 administered
      (a) intraperitoneally (i.p.) to male Sprague-Dawley (SD) rats for 4 days and (b)
      orally (PO) to male and female SD rats for 11 days. Compared to their respective
      controls, significant increases in GSTP-positive hepatocytes were observed in
      male rats administered FB1 i.p. at 10 mg/kg body weight/day for 4 days, as well
      as in male and female rats treated with 35 and 75 mg/kg body weight/day FB1 p.o.
      for 11 days. The percentage section area of liver occupied by GSTP-positive mini
      foci comprising of three to 12 cells was increased significantly in male rats
      given 10 mg/kg FB1 i.p., or in p.o.-treated males and females with 75 mg/kg FB1.
      Both i.p. and p.o. FB1 treatments resulted in dose-related enhanced hepatocyte
      proliferation as measured by proliferating cell nuclear antigen (PCNA) labeling
      with significant increases in the number of PCNA-positive nuclei at the same i.p.
      and p.o. dose levels where the number of GSTP-positive cells were elevated. In
      all studies, enhanced PCNA and GSTP expression occurred at FB1 doses which, based
      on serum biochemical and histopathological data previously reported from our
      laboratory, were shown to be hepatotoxic. Therefore, our data suggest that in a
      manner similar to known genotoxic carcinogens, FB1 has the capacity to initiate
      GSTP-positive hepatocytes with their subsequent development into GSTP mini-foci
      at exposure levels that induce enhanced hepatocyte proliferation in response to
      liver toxicity. In SD rats, this occurs as early as within 4 days of i.p.
      treatment or 11 days of p.o. treatment.

PMID- 9652791
TI  - Insulin-like growth factor II (IGF-II) secreted from HepG2 human hepatocellular
      carcinoma cells shows angiogenic activity.
AB  - Hepatocellular carcinoma (HCC) is a typical hypervascular tumor. Since insulin
      like growth factor II (IGF-II) has been reported to play a significant role in
      liver regeneration and hepatocarcinogenesis, we initially examined its angiogenic
      effect on the chorioallantoic membrane (CAM) of 9-day-old chick embryos. We also
      investigated whether IGF-II secreted from HepG2 human hepatocellular carcinoma
      cells induces vascularization using the chick embryo CAM. We found that the
      concentrated conditioned media (CCM) of HepG2 cell culture induced angiogenesis
      on the CAM. We also identified IGF-II protein in the CCM from HepG2 cells by
      Western blot analysis. However, CCM from Chang liver cells, which are normal
      human liver cells and were free of IGF-II, did not induce angiogenesis in the
      CAM. These results suggest that IGF-II secreted from hepatocellular carcinoma
      cells may act as an angiogenic factor for the hypervascularization of HCC.

PMID- 9652792
TI  - Loss of tumorigenicity of human pancreatic carcinoma cells engineered to produce
      interleukin-2 or interleukin-4 in nude mice: a potentiality for cancer gene
      therapy.
AB  - To examine the possibility of cytokine gene therapy in relation to pancreatic
      cancer, we evaluated the antitumor effect of human pancreatic carcinoma cells
      (AsPC-1) which were retrovirally-transduced with several kinds of cytokine genes.
      These cells were inoculated into BALB/c nude mice and their tumor volumes were
      assessed. The in vitro growth rate of the transduced cells was not different from
      that of a parental cell line. Among the transduced cells, human interleukin (IL)
      6-transduced AsPC-1 and mouse granulocyte macrophage colony-stimulating factor
      transduced AsPC-1 cells showed a significant retardation of tumor growth compared
      with a parental cell line. In the cases of AsPC-1 cells transduced with the human
      IL-2 or mouse IL-4 gene, small tumors were generated but thereafter they
      regressed completely. Histological examinations showed monocytic cell
      infiltration around the tumors of IL-2- or IL-4-producing cells. These data
      suggest that secretion of IL-2 or IL-4 from tumor cells can induce an antitumor
      effect even in the defective condition of mature T cells.

PMID- 9652793
TI  - Platelet-derived endothelial cell growth factor/thymidine phosphorylase
      expression correlated with tumor angiogenesis and macrophage infiltration in
      colorectal cancer.
AB  - To clarify whether platelet-derived endothelial cell growth factor/thymidine
      phosphorylase (PD-ECGF/TP) expression in both tumor cells and stromal cells has
      independent or synergistic effects on tumor angiogenesis and progression and to
      explore a possible regulator for PD-ECGF/TP expression, immunohistochemical
      staining was conducted on 148 specimens of colorectal cancer. The microvessel
      count was significantly correlated with the extent of PD-ECGF/TP expression.
      Macrophage infiltration in tumors with positive TP was significantly higher than
      in tumors with negative TP (P < 0.001). The Cox model showed that PD-ECGF/TP
      expression was an independent prognostic factor, although the microvessel count
      had a stronger value in determining the patient prognosis.

PMID- 9652794
TI  - Human melanoma metastasis is inhibited following ex vivo treatment with an
      antisense oligonucleotide to protein kinase C-alpha.
AB  - To determine whether alteration of PKC alpha expression would affect the
      metastatic potential of human melanoma cells, replicate cultures of C8161 cells
      were treated in vitro with a phosphorothioate antisense oligodeoxynucleotide
      (ODN) that specifically inhibits PKC alpha expression (ISIS-3521). Control C8161
      cultures were treated with a scrambled sequence ODN, cationic liposomes or were
      left untreated. Northern blots demonstrated 70% inhibition of PKC alpha mRNA in
      ISIS-3521-treated cells compared to controls. Metastasis was suppressed by 75%
      when ISIS-3521-treated cells were injected intravenously into athymic mice. These
      results show that PKC alpha expression is important in the regulation of human
      melanoma metastasis.

PMID- 9652795
TI  - A model of wound healing in chronically radiation-damaged rat skin.
AB  - The aim of this investigation was to develop a model for studying the chronic
      effects of radiation on wound healing in the rat. Six months after rats received
      a single radiation exposure of 20 Gy, a random-pattern dorsal skin flap was
      elevated. Two weeks after the flap was elevated, irradiated animals showed
      diminished scar formation and wound breaking strength, as compared with controls
      (P < 0.05). The effect of hyperbaric oxygen treatment was investigated in some
      rats who received 20 sessions at 2.4 atmospheres absolute for 90 min daily, 5
      days per week, prior to flap elevation and 10 sessions after creation of the
      flap. Treated animals showed a trend toward improvements in wound breaking
      strength and scar formation (P = 0.06). A reproducible model of chronic radiation
      damage in the rat was established. Further studies involving investigations at
      times more that 2 weeks post-wounding are needed.

PMID- 9652796
TI  - Kinetics of the inhibition of acetylcholinesterase in camel retina by cisplatin.
AB  - The inhibitory effect of cisplatin (CDDP) on camel retina acetylcholinesterase
      (AChE) was characterized. The CDDP effect was independent of the time of
      incubation with AChE before the addition of substrate, indicative of reversible
      inhibition. Moreover, dilution data prove that CDDP is a reversible inhibitor of
      camel retina AChE. Cisplatin inhibited AChE activity of camel retina in a
      concentration- and time-dependent manner, the IC50 values being 5.32 and 0.196 mM
      at 5 min and 24 h incubation times, respectively. The IC50 has dual components,
      i.e. directly proportional and inversely proportional to 0-1.5 h and 1.5-24 h
      incubation periods, respectively. The Michaelis-Menten constant (Km) for the
      hydrolysis of acetylthiocholine iodide (ASCh) was found to be 0.0796 mM and Vmax
      was 0.668 micromol/min/mg protein. Kmapp and Vmaxapp both decreased as the CDDP
      concentration increased. Dixon as well as Lineweaver-Burk plots and their
      secondary replots indicated that the nature of the inhibition was of the pure
      uncompetitive type. The value of Ki was estimated as 0.811 mM by the primary and
      secondary replots of the Lineweaver-Burk and Dixon plots. Kiapp decreased while
      Vmaxiapp increased after increasing the ASCh concentration.

PMID- 9652797
TI  - Variable Bcl-2 phenotype in benign and malignant lesions of urothelium.
AB  - We examined Bcl-2, Bax and p53 expression in transitional epithelium, benign
      lesions derived from transitional epithelium (Brunn's nests and inverted
      papillomas) and transitional cell cancer (TCC) of the upper urinary tract and
      urinary bladder using immunostaining of cryostat sections. We also performed
      Western blot analysis of normal urothelium and TCCs for Bcl-2 and p53.
      Immunohistochemical staining showed that Bcl-2 was expressed only on basal layer
      cells, whereas Bax expression was restricted to superficial layers in normal
      transitional epithelium. Benign lesions of the urinary bladder (Brunn's nests and
      inverted papillomas) showed strong immunoreactivity to Bcl-2. Taken together, 16
      (17%) TCCs were positive for Bcl-2, 62 (64.6%) TCCs were positive for Bax and 28
      (29%) TCCs were positive for p53. The expression of Bcl-2 on TCC had a
      statistical correlation with tumor stage, histopathologic grade and p53 protein
      accumulation. The results suggest that although Bcl-2 overexpression is detected
      in normal urothelium and benign lesions of the urinary bladder, it might also
      contribute to the high grade tumor malignancy of TCC.

PMID- 9652798
TI  - Prognostic value of mutations and a germ line polymorphism of the p53 gene in non
      small cell lung carcinoma: association with clinicopathological features.
AB  - The prognostic value of the mutation of the p53 tumor suppressor gene in non
      small cell lung carcinomas (NSCLC) is controversial and a polymorphism of the p53
      gene at codon 72 consisting of two alleles, arginine (Arg) and proline (Pro), has
      been reported to be associated with the incidence of smoking-related NSCLC. We
      have studied 67 cases of NSCLC in relation to the mutation of the p53 gene by
      polymerase chain reaction (PCR)-single-strand conformation polymorphism and 178
      cases in relation to the polymorphism of the gene by PCR using allele-specific
      primers. The genetic alterations of the p53 gene (from exons 5 to 9) were found
      in 34% of the patients. Frequent mutations were observed among younger patients
      (less than 65 years old), however, there is no significant correlation of the
      mutation with smoking history, histopathological types, clinical stages or
      prognosis. We observed that Arg/Arg homozygotes were frequently found in non
      smoking patients with NSCLC but Arg/Pro heterozygotes were infrequent in the
      group. There was no significant association of the polymorphic alleles with
      histopathological types, clinical stages or prognosis. Thus, the polymorphism of
      the p53 gene affects the predisposition of non-smokers to NSCLC, but the
      alteration of the p53 gene is independent of tumor progression and
      histopathology.

PMID- 9652799
TI  - Tumour necrosis factor-alpha does not cross the rat placenta.
AB  - In the last few years there has been a considerable proliferation of studies
      suggesting that tumour necrosis factor-alpha (TNF) has a very important
      physiological role in pregnancy. Its presence in the fetus has been related to
      several important roles such as cell growth and differentiation or immune
      protection. The aim of the present work was to analyze whether maternal TNF could
      reach the fetal circulation. The results found after in vivo [125I]TNF
      administration to pregnant rats at term demonstrate that, TNF does not cross the
      placenta and therefore it may be suggested that the cytokine which is found in
      the fetus is synthesized in its organs.

PMID- 9652800
TI  - Resistance factors in colon cancer tissue and the adjacent normal colon tissue:
      glutathione S-transferases alpha and pi, glutathione and aldehyde dehydrogenase.
AB  - Glutathione S-transferases (GST) alpha and pi, glutathione (GSH) and aldehyde
      dehydrogenase (ADH) were determined in colorectal cancer tissue specimens and in
      the adjacent normal colon tissue. The median contents in normal and cancer tissue
      were 8.1 (2.3-30.3) (5-95% quantiles) and 15.1 (5.3-50.3) microg/mg protein for
      GST pi (P = 0.035), 0.0 (0.0-1.4) and 0.4 (0.0-3.5) microg/mg protein for GST
      alpha (P = 0.019), 7.3 (1.3-22.7) and 5.6 (2.3-26.0) microg/mg protein for GSH (P
      = 0.171) and 30.8 (13.0-42.0) and 23.2 (9.0-32.9) microg/mg protein for ADH (P =
      0.0017), respectively. Thus, the mean GST alpha and pi both significantly
      increased in colon cancer compared to the adjacent normal tissue, which
      underlines their importance as possible resistance factors. A highly significant
      correlation was obtained between the GSH content in colon cancer and normal
      tissue (P = 0.0017). Thus, the constitutive GSH expression seems to be maintained
      during tumor development. A similar correlation was obtained for ADH (P =
      0.0075), but the median ADH was lower in cancer tissue compared to the adjacent
      normal tissue (P = 0.0017). Contrary to GSH and ADH, GST pi did not correlate
      between normal and colon cancer tissue. Whereas GSH and ADH correlated in normal
      colon tissue (P = 0.014), no significant correlation for GSH and ADH was observed
      in colon cancer tissue (P = 0.109). In conclusion, significant correlations
      between colon cancer and normal tissue were obtained, suggesting that the
      expression levels of these resistance factors are maintained during
      carcinogenesis in most patients.

PMID- 9652801
TI  - Human in vitro cell lines verification by minisatellite DNA restriction fragment
      length polymorphism.
AB  - Four families of human in vitro cell lines were tested for minisatellite
      restriction fragment length polymorphism (RFLP) using multilocus probes MZ1.3
      and/or 33.15 after digestion of DNA with restriction enzymes HinfI or HaeIII.
      These results confirmed that (i) the RFLP pattern is relatively stable in
      established cell lines and, therefore, could be used as a specific marker of a
      cell line identity, (ii) the use of MZ1.3 and 33.15 probes permits the
      identification of hybridomas and (iii) one of the cell lines tested, a
      lymphoblastoid cell line HAJ, may possess a hot spot of mutation.

PMID- 9652802
TI  - Mechanisms of induction of apoptotic DNA fragmentation.
AB  - PURPOSE: Despite its common use as an indicator of apoptosis, little is known
      about the mechanisms controlling apoptotic DNA fragmentation in irradiated cells.
      This review discusses the pathways of chromatin fragmentation, and the role of
      both nucleases and chromatin structure in this process. DEFINITIONS: DNA
      fragmentation linked to apoptosis is a combination of cleavage events excising
      both large DNA fragments within the range 0.4-1.0 Mbp and 50 kbp followed by
      random cuts within internucleosomal regions (i.e. DNA laddering). The first two
      cleavage steps can be detected in virtually all apoptotic cells, but DNA
      laddering is not ubiquitously observed. Endonucleases that mediate this cleavage
      of chromatin may be classified by substrate specificity, mode of DNA cleavage and
      their cofactor requirements. CONCLUSIONS: Three major pathways of DNA
      fragmentation are proposed and discussed: (1) upregulation of endonucleases, (2)
      their intranuclear/intracellular redistribution and (3) primary changes of
      chromatin structure.

PMID- 9652804
TI  - On the experimental distinction between ssbs and dsbs in circular DNA.
AB  - PURPOSE: To determine directly the minimal distance between two ssbs on
      complementary strands in circular DNA that are not observed as a dsb by
      electrophoresis. MATERIALS AND METHODS: 3.2 kbp DNAs with cohesive overhangs of
      various lengths were systematically generated by a newly devised method and
      electrophoresed in agarose slabs. RESULTS: At 4 degrees C, 3.2 kbp DNA with
      cohesive overhangs larger than 6 bp migrated as circular DNA. The minimal
      overhang size for the DNA to migrate as circular DNA was larger at 25 degrees C.
      Whether the DNA migrated as a circular or a linear molecule depended also on the
      nucleotide sequence of its overhangs, most notably at the minimal size.
      CONCLUSIONS: The minimal distance obtained in the present study agrees with the
      smaller values of previous indirect estimates. The dependence of the distance on
      experimental conditions suggests feasibility of obtaining the stagger-size
      distribution of radiation-induced dsbs.

PMID- 9652803
TI  - Reduced joining of DNA double strand breaks with an abnormal mutation spectrum in
      rodent mutants of DNA-PKcs and Ku80.
AB  - PURPOSE: To characterize further the contribution of the DNA-PK-dependent dsb
      repair pathway in mammalian cells. MATERIALS AND METHODS: The efficiency and
      fidelity of the joining of linear plasmids by DNA-PKcs-defective mouse cells
      (SCID) and Ku80-defective Chinese hamster ovary cells (xrs-6) was measured using
      either linear or circular replicating shuttle vector pZ189. RESULTS: The authors
      found a 3.9-10.7-fold reduced joining of the DNA ends, as compared with wild-type
      cells. Mutation analysis of the joining site revealed that the joining process
      was not hypermutable in the mutated cells. However, the SCID and xrs-6 cells
      produced a different spectrum of mutations at the joining site with a
      significantly lower proportion of insertions or more complex mutations.
      CONCLUSIONS: The remaining joining ability of the mutant cells points to an
      alternative DNA-PK-independent pathway of dsb repair. Comparison of these data
      with similar data from yeast suggest that the postulated alternative pathway of
      dsb repair is at least as efficient and less error-prone in rodent cells.

PMID- 9652805
TI  - In vitro rejoining of DNA double strand breaks: a comparison of genomic-DNA with
      plasmid-DNA-based assays.
AB  - PURPOSE: To evaluate potential similarities between the enzymatic activities
      required to rejoin DNA double strand breaks (dsb) in an in vitro assay based on
      genomic DNA and an in vitro assay based on plasmid DNA. Because the latter assay
      is simpler and faster, it should be preferred for the characterization of repair
      factors if both assays are found to probe for the same activities. If, however,
      the enzymatic requirements for dsb rejoining are different between the two
      assays, both should be used as they are likely to play complementary roles in the
      characterization of repair factors. MATERIALS AND METHODS: A cell-free assay has
      been used, developed to study rejoining DNA dsb induced by radiation in 'naked'
      DNA prepared from agarose embedded cells using an extract of HeLa cells as a
      source of enzymes. Also employed was an in vitro assay using the ligation of
      linearized plasmid DNA to model dsb rejoining. RESULTS: Evidence is presented
      that, under the conditions employed, different sets of activities are involved in
      the ligation of linearized plasmid DNA and in the rejoining of dsb in 'naked'
      genomic DNA. Optimal rejoining of dsb induced in genomic DNA is observed with
      cytoplasmic cell extract at 37 degrees C, whereas optimal ligation of plasmid DNA
      is observed with nuclear extract at 25 degrees C. Rejoining of dsb in genomic DNA
      comes to a near halt at 14 degrees C, but plasmid DNA ligation proceeds at
      significant rates at this temperature. Furthermore, the activities required for
      the rejoining of dsb induced in genomic DNA are partly stable to heating at 50
      degrees C for 1 h, whereas activities required for the ligation of plasmid DNA
      are completely inactivated by a similar treatment. Both reactions require ATP for
      optimal performance, and in both, DNA joining is inhibited at high ATP
      concentrations. CONCLUSIONS: These observations indicate that the plasmid-and the
      genomic-DNA-based assays probe for, at least partly, different sets of activities
      and therefore are expected to play complementary roles in the purification and
      characterization of activities involved in dsb rejoining.

PMID- 9652806
TI  - DNA damage induction and tumour cell radiosensitivity: PFGE and halo
      measurements.
AB  - PURPOSE: To test whether induction of DNA damage is correlated with tumour-cell
      radiosensitivity. MATERIALS AND METHODS: Initial DNA damage caused by X
      irradiation was measured in ten human tumour cell lines, which largely differed
      in radiosensitivity, using either the pulsed-field gel electrophoresis assay or
      the halo technique. RESULTS: None of the parameters of DNA damage correlated with
      any parameter of cellular radiosensitivity. This was not only true when the
      analysis was performed on all data but also when the analysis was performed after
      separating the cell lines into radioresistant and sensitive groups. Even when
      differences in chromosome number, ploidy and cell cycle distribution were taken
      into account, no significant correlations were obtained. CONCLUSIONS: Contrary to
      previous suggestions, differences in the number of double-strand breaks induced
      or chromatin-related 'presentation' of DNA lesions, measured by pulsed-field gel
      electrophoresis or halo respectively, are generally not the dominant factors
      determining tumour-cell radiosensitivity.

PMID- 9652807
TI  - Apoptosis induced by X-rays and chemical agents in murine fibroblastic cell lines
      with a defect in repair of DNA double-strand breaks.
AB  - PURPOSE: To investigate apoptosis in murine fibroblasts that are deficient in DNA
      double-stand breaks (dsb) repair. MATERIALS AND METHODS: BALB/c 3T3 cells and
      cells from a severe combined immunodeficient (scid) mouse were exposed to X-rays,
      UV light, bleomycin, etoposide or cisplatin. After exposure, the rate of
      apoptosis was assayed by propidium iodide staining based on characteristic
      morphological change. RESULTS: The scid cells, defective in dsb repair, were
      extremely sensitive to apoptosis induced by X-rays and bleomycin compared with
      BALB/c 3T3 cells. The scid cells were slightly sensitive to apoptosis induced by
      etoposide, an agent producing protein-associated dsb, and to apoptosis induced by
      agents not causing dsb. CONCLUSIONS: These studies show that sensitivity of cells
      to apoptosis induced by X-rays or bleomycin is enhanced by the scid mutation and
      that apoptosis induced by etoposide, which causes protein-associated dsb, is not
      greatly affected. There may be different processes involved in the induction of
      apoptosis by X-rays or bleomycin and etoposide.

PMID- 9652808
TI  - Radiosensitization of mouse sarcoma cells by fludarabine (F-ara-A) or gemcitabine
      (dFdC), two nucleoside analogues, is not mediated by an increased induction or a
      repair inhibition of DNA double-strand breaks as measured by pulsed-field gel
      electrophoresis.
AB  - PURPOSE: To investigate the effect of fludarabine (F-ara-A) and gemcitabine
      (dFdC), two radiosensitizing nucleoside analogues, on the induction and repair of
      DNA dsb after ionizing radiation. MATERIALS AND METHODS: Radiosensitization of
      mouse sarcoma SA-NH and FSA cells was studied using a clonogenic assay. Cell
      survival curves were fitted with the linear-quadratic model. DNA dsbs were
      detected by pulsed-field gel electrophoresis under neutral conditions. RESULTS: F
      ara-A (100 micromol dm(-3) for 1 h prior to irradiation) induced a substantial
      radiosensitization in SA-NH cells with a dose modification factor of 2.0 for a
      surviving fraction of 0.5. In a FSA mouse sarcoma cell line, dFdC (5 micromol dm(
      3) for 3 h prior to irradiation) induced a modest radiosensitization with a DMF
      of 1.2 for a surviving fraction of 0.5. Under similar experimental conditions,
      neither F-ara-A nor dFdC altered the yield of radiation-induced DNA dsbs in the
      dose range of 0-40 Gy. After a single dose of 25 Gy (SA-NH cells) or 40 Gy (FSA
      cells), neither the kinetics of repair nor the amount of residual damage was
      affected by F-ara-A or dFdC. CONCLUSIONS: For experimental conditions under which
      radiosensitization was observed, neither the induction nor the repair of DNA dsbs
      after ionizing radiation were affected by F-ara-A or dFdC.

PMID- 9652809
TI  - Estimate of true incomplete exchanges using fluorescence in situ hybridization
      with telomere probes.
AB  - PURPOSE: To study the frequency of true incomplete exchanges in radiation-induced
      chromosome aberrations. MATERIALS AND METHODS: Human lymphocytes were exposed to
      2 Gy and 5 Gy of gamma-rays. Chromosome aberrations were studied using the
      fluorescence in situ hybridization (FISH) technique with whole chromosome
      specific probes, together with human telomere probes. Chromosomes 2 and 4 were
      chosen in the present study. RESULTS: The percentage of incomplete exchanges was
      27% when telomere signals were not considered. After excluding false incomplete
      exchanges identified by the telomere signals, the percentage of incomplete
      exchanges decreased to 11%. Since telomere signals appear on about 82% of the
      telomeres, the percentage of true incomplete exchanges should be even lower and
      was estimated to be 3%. This percentage was similar for chromosomes 2 and 4 and
      for doses of both 2 Gy and 5 Gy. CONCLUSIONS: The percentage of true incomplete
      exchanges is significantly lower in gamma-irradiated human lymphocytes than the
      frequencies reported in the literature.

PMID- 9652810
TI  - Non-fluorescent chromosome painting using the peroxidase/diaminobenzidine (DAB)
      reaction.
AB  - PURPOSE: To develop and validate non-fluorescent chromosome painting for bright
      field microscopy using the peroxidase/diaminobenzidine (DAB) reaction. MATERIALS
      AND METHODS: Peripheral blood lymphocytes were taken from patients with uterine
      cancer who had received heavy-ion radiation therapy. Chromosome slides were
      treated with RNase and pepsin, denatured mildly, hybridized with a biotinylated
      DNA probe specific for whole-chromosome 4 and stained using the peroxidase/DAB
      reaction with an avidin-biotin amplification. The slides were analysed under a
      bright-field microscope and an atomic force microscope. The detection rate of
      chromosome aberrations by DAB painting was compared with that obtained by dual
      analysis of Giemsa staining and FISH painting. RESULTS: When chromosomes 4 were
      painted, 11.5% of unstable aberrations were detected by DAB painting, while 10.8%
      of them were found by dual analysis of Giemsa staining and FISH painting.
      CONCLUSION: A DAB painting method that can effectively detect rearranged
      aberrations was established. It has advantages over FISH painting: the
      preparations can be analysed by bright-field microscope, can be preserved
      permanently and are suitable for analysis by an automated system.

PMID- 9652811
TI  - Oral administration of tritiated water (HTO) in mouse. III: Low dose-rate
      irradiation and threshold dose-rate for radiation risk.
AB  - PURPOSE: To investigate the biological effect of tritium on mouse at low dose
      rates. MATERIALS AND METHODS: Mice ([C57BL/6N x C3H/He]F1) were exposed to beta
      rays by continuous administration of tritiated drinking water throughout their
      lives at low dose-rates of 3.6, 0.9, and 0.2 mG/day. RESULTS: Including the
      previous study, the tumour frequency was 70 to approximately 80% for exposure in
      the range 240 mGy/day to 9.6 mGy/day. Frequency of tumours decreased with
      decrease of dose-rate to 50% comparable to the controls. Restricting to thymic
      lymphomas, a linear relationship in a semi-log plot was found between the
      frequency and the dose-rate above a threshold dose-rate of 12 mGy/day. There was
      a 'tail' to this relationship down to 0.9 mGy/day. A similar pattern resulted for
      the relationship between the life-shortening and the dose-rate. The threshold
      dose-rate of 3H beta-rays, 2 mGy/day (with a tail down to 0.2 mGy/day), was much
      lower than that of gamma-rays, 20 mGy/day (tail down to 2 mGy/day) derived from
      other studies. CONCLUSIONS: These studies suggest that there exists the threshold
      dose-rate in the biological effects of radiation, and that the threshold dose
      rate for 60Co gamma-irradiation is higher than that for 3H beta-irradiation.

PMID- 9652812
TI  - Accidental intake of tritiated water: a cytogenetic follow-up case on
      translocation stability and dose reconstruction.
AB  - PURPOSE: To examine by fluorescence in situ hybridization (FISH) chromosomal
      translocations in a person who, 11 years previously, had accidentally
      incorporated tritiated water. To compare the resultant estimate of radiation dose
      with contemporary dosimetry made by urine analysis and dicentric chromosome
      scoring. MATERIALS AND METHODS: Blood lymphocytes were shared by two laboratories
      each performing the FISH analysis using different chromosome probe combinations.
      Doses were calculated by reference to an in vitro calibration curve produced in
      one of the laboratories. RESULTS: Good agreement in translocation yields was
      found by the two laboratories. Comparing the yields with the dicentric frequency
      obtained shortly after the accident and with a translocation frequency measured 6
      years post exposure showed good agreement between all measurements. This
      indicates essentially perfect stability for translocations over an 11 year period
      in this individual. CONCLUSIONS: Dose reconstruction based on FISH-measured
      translocations showed good agreement with the dose estimated from initial
      dicentric measurements and from measurements of tritium in urine. Because of the
      extensive initial dosimetry performed on this individual, who received a uniform
      whole-body irradiation, the case serves as an excellent test for the use of FISH
      measured translocations for retrospective biodosimetry.

PMID- 9652813
TI  - Micronucleus frequencies in cytokinesis-blocked human B lymphocytes after low
      dose gamma-irradiation.
AB  - PURPOSE: To investigate (1) the radiosensitivity of B versus T lymphocytes with
      respect to micronucleus (MN) induction and (2) the possible application of the B
      cell MN assay for biological dosimetry of individuals after acute exposure to low
      doses of ionizing radiation. MATERIALS AND METHODS: MN analysis was performed in
      T and B lymphocytes of six healthy volunteers exposed in vitro to gamma-ray doses
      ranging from 0.05 Gy to 1 Gy. For the MN assay on B cells, peripheral blood
      mononuclear cells were cultured and stimulated with pokeweed mitogen (PWM).
      Afterwards the B lymphocytes (characterized by the CD20+ phenotype) were
      separated with the FACSort flow cytometer and the number of MN in the sorted
      binucleate cells was scored. For T lymphocytes the standard MN protocol was
      applied. RESULTS: The number of spontaneous and radiation induced MN were
      significantly higher in B lymphocytes compared to T lymphocytes in the low dose
      range up to 1 Gy. An analysis of the present data showed that when the
      spontaneous MN frequencies are not known, doses from 0.08 Gy could be detected
      with the B cell MN assay while the conventional MN assay only allowed detection
      of doses > 0.25 Gy. However, in contradiction to the linear-quadratic dose
      response for T cells, for B cells the initial steep increase of the MN yield with
      the very low dose was followed by a flattening of the curve towards higher doses.
      CONCLUSION: This study shows that B lymphocytes express a high number of MN for
      doses up to 1 Gy gamma-rays reflecting the highly radiosensitive behaviour of B
      cells. The results also point to the possible application of the B-cell MN assay
      for individual dose assessment. When blood samples can be taken within 24 h after
      acute accidental overexposure, the B-cell MN assay can be performed but only as a
      supplementary test to the conventional MN assay.

PMID- 9652814
TI  - Irradiation of Crotalus durissus terrificus crotoxin with 60Co gamma-rays induces
      its uptake by macrophages through scavenger receptors.
AB  - PURPOSE: To investigate the action of 2 kGy 60Co gamma-rays on crotoxin and its
      favoured uptake through scavenger receptor (ScvR) mouse peritoneal macrophages.
      MATERIALS AND METHODS: Native or irradiated crotoxin (iCTX) (50 microg/ml) dosed
      with 2 kGy 60Co gamma-rays (dose-rate 540 Gy/h) were offered to mouse peritoneal
      macrophages; their uptake was evaluated by immunohistochemistry and quantitative
      in situ ELISA. Receptors recognizing irradiated crotoxin were evaluated with
      specific ScvR blockers (Probucol and dextran sulphate) or with non-specific
      blocking using foetal calf serum (FCS). RESULTS: Immunohistochemical assays
      revealed more deeply staining intracytoplasmic vacuoles in macrophages incubated
      with iCTX. Using in situ ELISA with ScvR specific blockers, it was shown that the
      increased uptake of iCTX was blocked by Probucol or dextran sulphate, but not by
      FCS. On the other hand, the uptake of native crotoxin was decreased by FCS, but
      not affected by ScvR blockers. The morphology and viability of macrophages were
      preserved during the experiments. CONCLUSIONS: It is concluded that 60Co gamma
      rays probably induced oxidative changes in crotoxin, driving this toxin towards
      ScvR mouse peritoneal macrophages. This suggests a different in vivo route of
      iCTX away from toxic neural sites by a preferential and rapid internalization and
      processing by macrophages, leading to the induction of a better immune response.

PMID- 9652815
TI  - Labelling of bleomycin with Auger-emitter increases cytotoxicity in squamous-cell
      cancer cell lines.
AB  - PURPOSE: To investigate the cytotoxicity of bleomycin (BLM), two Auger-emitting
      bleomycin complexes (indium-111 ((111)In)-BLMC) and (111)InCl3 in three squamous
      cell cancer (SCC) cell lines. MATERIAL AND METHODS: Three recently established
      SCC cell lines were investigated using the 96-well clonogenic assay.
      Concentrations causing 50% inhibition in cell survival (IC50) were calculated for
      BLM and two specific activities of (111)In-BLMC (40 MBq/mg BLM (low) and 195
      MBq/mg BLM (high)). RESULTS: (111)In-BLMC (low) was the most toxic to the SCC
      cell lines. (111)In-BLMC containing 4.9-fold more activity of (111)In (195 MBq/mg
      BLM) was more effective than BLM (p=0.0029), but not as toxic as (111)In-BLMC
      (low) (p=0.0023). UT-SCC-19A had a IC50 value for BLM as low as 4.1 nM, whereas
      IC50 values for (111)In-BLMC (low) and (111)In-BLMC (high) were 2.0 nM and 2.6
      nM, respectively. The most chemoresistant cell line UT-SCC-12A had a IC50 value
      for BLM of 18.8 nM, for (111)In-BLMC (low) 10.7 nM and for (111)In-BLMC (high)
      12.7 nM. (111)InCl3 had no cell killing effect. CONCLUSIONS: This study shows
      that (111)In-BLMC is superior in SCC cell killing compared with BLM. These data
      provide the basis for further clinical investigations of (111)In-BLMC.

PMID- 9652816
TI  - Comment on the paper: Quantifying the position and steepness of radiation dose
      response curves.

PMID- 9652817
TI  - Comments on the paper: Cell survival in irradiated microcolonies: how influential
      are the neighbours?

PMID- 9652818
TI  - Comment on the paper: High-voltage overhead lines and radon daughter deposition.

PMID- 9652819
TI  - Dismantling in cell death: molecular mechanisms and relationship to caspase
      activation.
AB  - The notion of a cell death programme was introduced in view of the
      reproducibility of its occurrence in time and space (e.g. in the developing
      embryo) and of its genetic determination. Programmed cell death can be
      schematically subdivided into three steps: a signalling phase, an execution phase
      and a dismantling phase. This review focuses on the latter. Apoptosis is the most
      studied form of dismantling of animal cells. The molecular pathways leading to
      certain apoptotic lesions appear to be dependent on the proteolytic activity of
      caspases. Death itself can, however, be caspase-independent. Also, non-apoptotic
      forms of cell death exist, even in animal cells; their molecular bases are still
      unknown. The relationship between cell death, apoptosis and caspases is
      discussed.

PMID- 9652820
TI  - Infiltration patterns of short- and long-term cultured A-NK and T-LAK cells
      following adoptive immunotherapy.
AB  - Direct contact between lymphokine-activated killer (LAK) cells and tumour cells
      is believed to be imperative for initiating tumour cell lysis in vitro as well as
      in vivo. In order to optimize adoptive immunotherapy (AIT) it is therefore
      desirable to identify the LAK cell subtype, which ensures maximal infiltration of
      tumours as well as a substantial cytotoxic reactivity. In this report we have
      compared short- and long-term cultured murine adherent natural killer (A-NK)
      cells and mitogen-stimulated, lymphokine-activated T-killer (T-LAK) cells with
      respect to their proliferative potential, cytotoxicity, requirement for
      interleukin-2 (IL-2) and ability to infiltrate B16 pulmonary metastases following
      adoptive transfer. We found that short-term (5 days) cultured A-NK and T-LAK
      cells both showed a substantial accumulation of tumour tissues. However, A-NK
      cells gradually lost this ability during in vitro culture whereas T-LAK cells
      cultured for as long as 20 days retained their ability to infiltrate metastases
      as efficiently as their short-term cultured counterparts. Moreover, the low
      requirement of IL-2 by T-LAK cells to achieve maximal infiltration of tumours
      sharply contrasted with the excessive doses necessary to ensure maximal
      infiltration by A-NK cells. In conclusion, these data demonstrate that short-term
      cultured LAK cells of both NK- and T-cell origin are able to infiltrate B16
      pulmonary metastases effectively. Importantly, the T cells retain this ability
      for a considerably longer time and require much less IL-2 support than do A-NK
      cells, making T-LAK cells attractive for AIT.

PMID- 9652821
TI  - Antigen receptor cross-linking by anti-immunoglobulin antibodies coupled to cell
      surface membrane induces rapid apoptosis of normal spleen B cells.
AB  - Cross-linking of surface immunoglobulin (sIg) has been shown to induce either
      activation or apoptosis of mature B cells presumably depending on the nature of
      antigens. However, the nature of antigens for induction of mature B-cell
      apoptosis is not yet fully understood. We cross-linked sIg of mature B cells with
      various amounts of either anti-Ig antibodies in the soluble form or anti-Ig
      coupled to erythrocytes or myeloma cells as surrogate membrane-bound antigens.
      Anti-Ig antibodies coupled to cell surface membrane induced rapid and extensive
      apoptosis of normal spleen B cells even in the absence of signalling via the Fc
      receptor. In contrast, soluble anti-Ig induced proliferation or apoptosis of
      mature B cells depending on the concentration of anti-Ig. The extent of apoptosis
      induced by soluble anti-Ig was limited compared to that induced by membrane-bound
      anti-Ig. These results suggest that mature B cells undergo apoptosis or
      proliferation depending on whether antigens are soluble or membrane-bound and on
      antigen doses.

PMID- 9652822
TI  - Protective effect of beta-glucan against mycobacterium bovis, BCG infection in
      BALB/c mice.
AB  - Beta-1,3-glucan is a potent stimulator of macrophage functions and has a
      protective effect against a range of infections in rodent models. We examined
      whether the agent could also protect against the intracellular Mycobacterium
      bovis, bacillus Calmette-Guerin (BCG) infection in mice. BCG-susceptible BALB/c
      mice were injected intravenously (i.v.) with beta-glucan or vehicle 3 days
      before, or with beta-glucan 7 days after i.v. challenge with live BCG bacilli.
      The animals were killed 4 or 8 weeks later, their organs were homogenized and
      applied to object slides and stained with auramin for counting of bacilli, or
      seeded onto agar in Petri dishes. Mice treated with beta-glucan both pre- and
      postchallenge had significantly lower numbers of BCG bacilli and BCG colony
      forming units in spleen homogenates compared with controls 4 weeks after
      challenge. A similar, but not statistically significant, tendency was observed in
      spleen homogenates from mice killed 8 weeks after challenge. In homogenates of
      liver and lungs there were similar findings, but less pronounced. There was a
      dose-dependent effect of beta-glucan injected before BCG challenge on the number
      of BCG bacilli found in spleen and liver homogenates. In addition, antibody cross
      reactivity was demonstrated between M. tuberculosis cell wall and beta-glucan.
      The results suggest that beta-glucan has a protective effect against M. bovis,
      BCG infection in susceptible mice.

PMID- 9652823
TI  - Expression of interferon-gamma, interleukin-4 and interleukin-5 mRNA in the nasal
      mucosal membrane of rats with allergic rhinitis.
AB  - The production of immunoglobulin E (IgE) antibody is largely dependent on the
      ratio between interleukin-4 (IL-4) (a T helper 2 (Th2)-type cytokine) and
      interferon-gamma (IFN-gamma) (a T helper 1 (Th1)-type cytokine). Interleukin-5
      (IL-5) (also a Th2-type cytokine) is an important eosinophil differentiation
      factor and also co-stimulates B-cell growth and differentiation. The present
      study was designed to evaluate and compare the expression of IFN-gamma, IL-4 and
      IL-5 mRNA in the nasal mucosal membrane of sensitized Brown-Norway (BN) rats.
      Fourteen BN rats were divided into two groups: non-sensitized (control) and
      sensitized. The sensitized group was injected with ovalbumin (OA)
      intraperitoneally on three consecutive days. Twenty-one days later, rats were
      exposed to 1% OA aerosol. Twenty-four hours after exposure to aerosol, nasal
      mucosa was extracted from both groups and reverse transcriptase-polymerase chain
      reaction (RT-PCR) was performed. The densities of the bands of IL-4, IL-5 and IFN
      gamma mRNA were expressed as percentages against beta-actin mRNA. Our results
      showed that the mean values for IL-4 and IL-5 mRNA were increased significantly
      in sensitized rats compared with control rats. In contrast, the mean value for
      IFN-gamma mRNA was significantly lower in sensitized rats compared with those of
      the control group. Our data therefore suggest that sensitization of rat nasal
      mucous membranes results in the predominant expression of Th2-type cytokines.

PMID- 9652824
TI  - A peptide-binding assay for the disease-associated HLA-DQ8 molecule.
AB  - The study of peptide binding to HLA class II molecules has mostly concentrated on
      DR molecules. Since many autoimmune diseases show a primary association to
      particular DQ molecules rather than DR molecules, it is also important to study
      the peptide-binding properties of DQ molecules. Here we report a biochemical
      peptide-binding assay for the type I diabetes-associated DQ8, i.e. DQ
      (alpha1*0301, beta1*0302), molecule. Affinity-purified DQ8 molecules were tested
      in peptide-binding assays using a radiolabelled influenza haemagglutinin (Ha)
      peptide encompassing positions 255-271(Y) as an indicator peptide. The Ha 255
      271(Y) peptide bound to DQ8 in a pH-dependent fashion showing optimal binding
      around pH 5. The association kinetics were relatively slow and the resulting
      complexes were heat labile. The specificity of peptide binding to DQ8 was
      investigated in competitive inhibition experiments with a panel of 43 peptides of
      different lengths and sequences. The DQ8 molecules showed a different pattern of
      peptide binding compared to a previously studied DQ2 molecule. Peptides derived
      from thyroid peroxidase, HLA-DQ(alpha1*0301), HLA-DQ(alpha1*0302), retinol
      receptor and p21ras were among the high-affinity binders, whereas peptides
      derived from myelin basic protein were among the low-affinity binders. The
      sequence of the high-affinity peptides conformed with a previously published
      peptide-binding motif of DQ8.

PMID- 9652825
TI  - Immunoglobulin prolongs survival of pig kidneys perfused ex vivo with human
      blood.
AB  - Intravenous immunoglobulin (IVIG) (Octagam), was used to determine the effect on
      hyperacute rejection in an ex vivo xenograft model. Six pig kidneys were perfused
      with IVIG and fresh human AB blood, and six control pig kidneys were
      simultaneously perfused with albumin and blood from the same donation. The
      survival of the IVIG-perfused xenografts (median, 6.5 h) was significantly (P =
      0.03) longer than the albumin-perfused xenografts (median, 3.5 h). Complement was
      activated in both groups. The administration of IVIG to the perfused blood
      resulted in immediate and significantly higher complement activation in the fluid
      phase as compared with the albumin group. At rejection the fluid phase complement
      activation was higher in the IVIG group than in the albumin group for C1rs/C1inh
      complexes, C4bc, Bb and TCC. At the time of rejection both the albumin and the
      IVIG group demonstrated interstitial tubular haemorrhage, vasculitis or necrosis
      of glomerular capillaries and glomerular microthrombi. IgM, C1q, C3c, C4 and
      fibrin were located in arteries and glomeruli and IgG in the interstitium in both
      groups at rejection. The fluid phase findings are consistent with a modulatory
      effect of IVIG on complement activation by deviating the classical pathway
      activation towards the fluid phase. The prolonged survival of the IVIG-perfused
      kidneys suggests that IVIG may be useful to dampen hyperacute rejection.

PMID- 9652826
TI  - IgG subclasses in Lyme borreliosis: a study of specific IgG subclass distribution
      in an interferon-gamma-predominated disease.
AB  - Lyme borreliosis has shown a T helper type 1 (Th1)-like immune response with high
      production of interferon-gamma. Since the cytokine environment seems to be
      important in the regulation of immunoglobulin production and in the switch
      between different isotypes and subclasses, and since the subclasses of IgG have
      different functions, we wanted to examine the IgG subclass distribution in Lyme
      borreliosis. We have developed an ELISA measuring flagellin-specific antibodies
      of the different IgG subclasses in serum and cerebrospinal fluid (CSF). Thirty
      five seropositive patients with varying manifestations of Lyme borreliosis were
      included in the study. According to the results, the predominating subclasses in
      both serum and CSF were IgG1 and IgG3. In samples taken early in disease this
      pattern was more pronounced in patients with a subacute disease, defined as
      recovery within 3 months, compared to patients that later on developed chronic
      borreliosis. The levels of IgG2 were generally low and IgG4 was below detection
      level. Thus, in the IFN-gamma-predominated immune response seen in Lyme
      borreliosis, mainly IgG1 and IgG3 were found, i.e. the subclasses that are
      complement activating as well as opsonizing in humans. Increased levels of these
      two subclasses early in disease might contribute to recovery and counteract the
      development of chronicity. The absence of IgG4 is in accordance with the presumed
      Th1-like situation of Lyme borreliosis.

PMID- 9652827
TI  - Interleukin-12 and perforin mRNA expression is augmented in blood mononuclear
      cells in multiple sclerosis.
AB  - Cytokines are suggested to orchestrate an abnormal immune response in multiple
      sclerosis (MS). The regulatory cytokine interleukin (IL)-12 induces T-helper (Th)
      cell switch to the Th1 type and the production by cytotoxic T cells of perforin,
      a cell lysis-inducing factor. It has been suggested that Th1-like cytokines may
      promote the development of MS, and the production of perforin to induce
      oligodendrocyte damage. In-situ hybridization with radiolabelled synthetic
      oligonucleotide probes was used to detect and enumerate mononuclear cells (MNC)
      expressing IL-12 and perforin mRNA in blood and cerebrospinal fluid (CSF) from
      patients with MS and controls. Plasma and CSF levels of IL-12 (p70) were
      evaluated by ELISA. Higher numbers of IL-12 and perforin mRNA-expressing MNC were
      registered in blood in MS and also in controls with aseptic meningoencephalitis
      (AM) compared to healthy subjects. There were a few patients with other non
      inflammatory neurological diseases who also had high levels of IL-12 or perforin
      mRNA expressing blood MNC. A parallel elevation was observed for IL-12 (p70)
      concentrations in plasma. In the MS patients' CSF, there was a further
      augmentation of IL-12 mRNA expressing MNC. To evaluate autoantigen-induced IL-12
      and perforin mRNA expression, blood MNC were cultivated +/- myelin basic protein
      (MBP), a candidate autoantigen in MS. Higher numbers of MBP-reactive IL-12 and
      perforin mRNA expressing blood MNC were detected in MS than controls. The
      augmentation of both IL-12 and perforin in MS might reflect ongoing inflammatory
      processes in MS and could represent targets for future treatments.

PMID- 9652828
TI  - Increased levels of soluble tumour necrosis factor receptor-I (P55) and decreased
      IgG1 reactivities in HIV-1 patients with cytomegalovirus disease.
AB  - The purpose of the study was to investigate potential associations between tumour
      necrosis factor (TNF), soluble TNF receptors (sTNF-Rs), immunoglobulin (Ig)G
      subclasses and development of cytomegalovirus (CMV) disease amongst human
      immunodeficiency virus (HIV)-1 patients. We enrolled HIV-1 patients with CD4
      counts less than 100/microl in a prospective study and followed them over 1 year
      for development of CMV disease. Concentrations of TNF, sTNF-RI, sTNF-RII and IgG
      subclass reactivities were measured by ELISA; levels of CMV pp65 antigenaemia
      were determined as numbers of pp65 expressing cells/100,000 cells and were
      measured by staining of leucocytes; and HIV-1 RNA loads were measured by
      polymerase chain reaction (PCR). Eighteen patients studied with CMV disease had
      higher levels of sTNF-RI than 18 similar patients without CMV disease.
      Concentrations of sTNF-RI correlated with levels of CMV antigenaemia in blood
      samples collected before the development of CMV disease. Patients with CMV
      disease had lower levels of IgG1 reactivities to CMV than patients without CMV
      disease. We conclude that increased levels of sTNF-RI and decreased IgG1
      reactivities are associated with an increased risk of development of CMV disease
      among HIV-1 patients.

PMID- 9652829
TI  - Allergen-induced synthesis of interleukin-5, but not of IgE, is a key mechanism
      linked to symptomatic episodes of seasonal allergic rhinitis in sensitized
      individuals.
AB  - Some individuals with detectable levels of Japanese cedar (Criptomeria japonica)
      pollen-specific immunoglobulin (Ig)E in serum have no apparent nasal symptoms
      during the pollen season. The response of CD4+ T-helper (Th) cells to the pollen
      allergen might differ fundamentally between asymptomatic and symptomatic
      individuals who are already sensitized to the pollen. The aim of this study was
      to discern the possible differences in responses of peripheral blood mononuclear
      cells (PBMCs) to the pollen allergen between asymptomatic and symptomatic
      subjects who have been sensitized to the pollen. This study included 20 non
      atopic healthy volunteers (non-atopic group) and 48 patients who had detectable
      levels of the pollen-specific IgE before the pollen season in 1997. In the review
      of nasal symptoms during the pollen season 1997, 24 patients had typical symptoms
      of seasonal allergic rhinitis (symptomatic group), and the remainder had no
      seasonal aggravation of nasal symptoms (asymptomatic group). Peripheral blood
      mononuclear cells (1.0 x 10(7) cells/well) were obtained from each individual
      during the pollen season and cultured in the absence or presence of 12.5 microg
      of Cry j 1 for 4 days. The concentrations of IgE, interleukin-5 (IL-5), and
      interferon-gamma (IFN-gamma) in the culture supernatants were measured. The
      levels of IgE produced by Cry j 1-stimulated PBMCs of the asymptomatic and
      symptomatic groups were significantly higher than those of the non-atopic group,
      but did not differ between the asymptomatic and symptomatic groups. The levels of
      IL-5 produced by Cry j 1-stimulated PBMCs did not differ significantly between
      the non-atopic group and the asymptomatic group, but the levels of IL-5 were
      significantly higher in the symptomatic group than in the asymptomatic group as
      well as the non-atopic group. The levels of IFN-gamma produced by Cry j 1
      stimulated PBMCs did not differ significantly among the three groups. In
      conclusion, our study has suggested that Japanese cedar pollen-induced synthesis
      of IL-5, but not of IgE or IFN-gamma, is likely to be a key mechanism linked to
      the symptomatic episode of seasonal allergic rhinitis in individuals sensitized
      to the pollen.

PMID- 9652830
TI  - Neutralization susceptibility of B subtype variant B" primary HIV-1 isolates. The
      HEC/FIOCRUZ AIDS Clinical Research Group.
AB  - Susceptibility to autologous and heterologous neutralization of primary human
      immunodeficiency virus (HIV)-1 isolates belonging to subtype B, to the B"-variant
      of subtype B or to subtype F from infected individuals residing in Rio de Janeiro
      was assayed. A lower infectivity of the B"- and F isolates when compared to the
      classical B-subtype HIV-1 isolates was observed. Comparisons of neutralization
      susceptibilities were carried out for 19 B-subtype, 11 B"-variant and two F
      subtype HIV-1 isolates with plasma from autologous and heterologous samples.
      Frequency of autologous neutralization was slightly lower for B-subtype isolates
      in comparison to B"-variant isolates. Heterologous intra-subtype neutralization
      was significantly lower for B-subtype than for the B"-variant or the F-subtype
      isolates. While B-subtype isolates were neutralized by most anti-F-subtype
      plasma, F-subtype isolates, although most susceptible to F-subtype antibodies,
      were highly susceptible to neutralization by anti-B-subtype antibodies. Cross
      neutralization for B"-variant and B-subtype isolates was not as extensive as
      observed for B- and F-subtype isolates. However, the results presented indicate a
      quite extensive cross-neutralization between Brazilian HIV-1 isolates.

PMID- 9652831
TI  - Placental transfer of IgG and IgG subclass antibodies anti-purified Escherichia
      coli LPS O16, O6 and O111.
AB  - We evaluated 22 paired maternal and cord sera regarding the presence of IgG and
      IgG subclasses against purified Escherichia coli LPS O6, O16 and O111 employing
      ELISA for titre and avidity analysis, isoelectric focusing associated with
      affinity-blotting for spectrotypic analysis, and the Western-blotting technique
      for recognition of the various bands in lipopolysaccharide (LPS). Levels of anti
      LPS IgG antibodies in cord sera were equivalent to their respective maternal
      sera, showing a significant correlation (P < 0.0001). IgG1 antibody levels were
      higher in cord sera than in maternal sera (P < 0.005 for anti-O111, P < 0.05 for
      anti-O16 and P < 0.02 for anti-O6). Cord IgG2 antibody levels were not different
      from the maternal levels (P > 0.1). The levels of IgG3 and IgG4 were
      undetectable. The avidity of anti-O6 and anti-O111 IgG in 10 cord sera showed an
      extremely significant correlation with maternal antibody avidity (P < 0.0001).
      Identical patterns of recognition were found in the paired samples analysed by
      Western blotting. Most of the serum samples recognized the O-repetitive chains
      and also the region corresponding to core and lipid A. Although the antibody
      spectrotypes varied among individuals, paired cord and maternal serum samples
      showed identical patterns. Our findings suggest the occurrence of placental
      transfer of IgG antibodies against LPS O6, O16 and O111, mainly involving the
      IgG1 or IgG2 subclasses.

PMID- 9652832
TI  - Effect of combined transient androgen deprivation and irradiation following
      radical prostatectomy for prostatic cancer.
AB  - PURPOSE: To evaluate whether transient androgen deprivation improves outcome in
      patients irradiated after radical prostatectomy for locally advanced disease,
      persistent or rising postoperative prostate specific antigen (PSA), or local
      recurrence. METHODS AND MATERIALS: Records of 105 consecutive patients who were
      treated with pelvic irradiation after radical retropubic prostatectomy between
      August 1985 and December 1995 were reviewed. Seventy-four patients received
      radiation alone (mean follow up: 4.6 years), and 31 received transient androgen
      blockade with a gonadotropin-releasing hormone agonist (4) androgen receptor
      blocker (1) or both (24) beginning 2 months prior to irradiation (mean follow-up
      3.0 years) for a mean duration of 6 months. Two of these patients were excluded
      from further analysis because they received hormonal therapy for more than 1
      year. Patients received a prostatic fossa dose of 60-70 Gy at 2 Gy per fraction;
      48 patients also received pelvic nodal irradiation to a median dose of 50 Gy.
      Survival, freedom from clinical relapse (FFCR), and freedom from biochemical
      relapse (FFBR) were evaluated by the Kaplan-Meier method. Biochemical relapse was
      defined as two consecutive PSA measurements exceeding 0.07 ng/ml. RESULTS: At 5
      years after irradiation, actuarial survival for all patients was 92%, FFCR was
      77%, and FFBR was 34%. FFBR was significantly better among patients who received
      transient androgen blockade before and during radiotherapy than among those
      treated with radiation alone (56 vs. 27% at 5 years, p = 0.004). FFCR was also
      superior for the combined treatment group (100 vs. 70% at 5 years, p = 0.014).
      Potential clinical prognostic factors before irradiation did not differ
      significantly between treatment groups, including tumor stage, summed Gleason
      histologic score, lymph node status, indication for treatment, and PSA levels
      before surgery or subsequent treatment. Multivariate analysis revealed that
      transient androgen deprivation was the only significant predictor for biochemical
      failure. CONCLUSION: This retrospective study of irradiation after radical
      prostatectomy suggests that transient androgen blockade and irradiation may
      improve freedom from early biochemical and clinically evident relapse compared to
      radiotherapy alone, although more prolonged follow-up will be needed to assess
      durability of impact upon clinical recurrence and survival rates.

PMID- 9652833
TI  - Radiotherapy of bladder cancer: relevance of bladder volume changes in planning
      boost treatment.
AB  - PURPOSE: This study aims to evaluate tumor motion with controlled changes of the
      bladder volume, and to assess the reproducibility of bladder (and tumor) position
      using a urinary catheter balloon as an immobilization device. METHODS AND
      MATERIALS: First, three patients with tumor growths in three different bladder
      regions (trigone, left lateral wall, anterior wall) were evaluated. Three
      dimensional CT-based reconstructed images were used to measure the displacement
      of the tumors when 100 cc were removed from a bladder originally filled with 170
      cc of contrast. The 3D calculated boost beam arrangements and field sizes for the
      three tumors in the partially emptied bladders were used to simulate treatment of
      the same tumors in the maximally filled bladders. Dose-volume histograms were
      obtained. Second, verification of an ellipsoid model for bladder volume changes
      was undertaken in 41 patients. Third, in eight additional patients a urinary
      catheter balloon filled with 80-cc sterile saline solution was used in an attempt
      to reproduce the shape and spatial coordinates of the bladder during the boost
      treatment. A pair of orthogonal films with the 80-cc balloon filled with contrast
      material were taken at simulation and repeated twice at weekly intervals during
      radiotherapy. The reproducibility was quantified by sequentially calculating the
      common surface of the bladder images in each orthogonal view. RESULTS: Target
      motion, especially in the craniocaudal axis, appeared to be more relevant for
      tumors arising in the bladder walls (15 mm) than in the trigone (5 mm).
      Underdosage (<95% of the prescribed dose to the target volume) was observed in
      20, 20, and 50% (with 1 cm margins around the tumor) and in 10, 10, and 15% (with
      1.5 cm margins around the tumor) of the tumors arising in the trigone, left
      lateral wall, and anterior wall, respectively. The ellipsoidal model was
      validated with a strong correlation coefficient allowing to establish a
      predictive model for bladder wall displacements as a function of bladder volume.
      In the balloon reproducibility study, mean reproducibility factors of 0.84 (+/
      0.06) and 0.82 (+/-0.07) were obtained for both anteroposterior and lateral
      views, respectively. CONCLUSIONS: Changes in bladder volume and shape related to
      bladder filling can result in clinically significant displacements of the target
      volume. A minimum of 2-cm margins around the target may compensate for extreme
      bladder volume changes during boost treatment. An ellipsoidal model for the
      bladder is consistent with these observations. Although an 80-cc urinary catheter
      balloon helped to immobilize the bladder, reproducibility was less than perfect.

PMID- 9652834
TI  - Granulocyte macrophage-colony-stimulating factor mouthwashes heal oral ulcers
      during head and neck radiotherapy.
AB  - PURPOSE: To evaluate the effectiveness of granulocyte macrophage-colony
      stimulating factor GM-CSF mouthwashes in the epithelization of radiation-induced
      oral mucosal ulceration, control of pain, and weight loss. METHODS AND MATERIALS:
      Twelve patients received curative radiotherapy for head and neck carcinoma. All
      had oropharyngeal and/or oral mucosa irradiation, with a median dose of 72 Gy
      (range 50-74), with conventional fractionation. A total of 300 microg of GM-CSF
      in 250 cc of water for 1 h of mouthwashing was prescribed. The procedure started
      once oral ulceration in the irradiation field was detected. Patients, examined
      twice a week, were evaluated for oral ulceration, pain, and weight loss. Blood
      tests were taken weekly during GM-CSF administration. A comparison was carried
      out with 12 retrospective case-matched controls. RESULTS: In the GM-CSF group,
      mucosa ulcerations healed in 9 of 12 (75%) of the patients during the course of
      the radiotherapy. Fifty percent of the patients said they felt less pain during
      the GM-CSF treatment; 30% needed morphine. The mean and median weight loss as a
      percentage of baseline weight in addition to the actual weight were 4.2% and 3%,
      respectively (variation ranged between a gain of 1% and a loss of 13%). No GM-CSF
      related side effects were found. In the case control group, in the 12 cases, oral
      ulcerations increased during radiotherapy and two patients needed intubation
      intake and hospital admission, as opposed to the GM-CSF group. The mean and
      median percentage of weight loss were 5.8% and 5%, respectively. Sixty percent of
      patients needed morphine, as opposed to 30% in the GM-CSF group. CONCLUSIONS:
      Granulocyte macrophage-colony-stimulating factor was effective in curing mucosal
      ulcerations during the course of radiotherapy. This is the first time we have
      seen a drug with this capacity. Although the GM-CSF seems to be effective in the
      control of pain, oral intake, and weight loss, we need further studies with a
      greater number of patients to confirm our premise. Double-blind trials are
      necessary for future research into the control of pain and weight loss.

PMID- 9652835
TI  - Prognostic features and treatment outcome in locoregionally advanced
      nasopharyngeal carcinoma following concurrent chemotherapy and radiotherapy.
AB  - PURPOSE: Concurrent chemotherapy and radiotherapy (CCRT) are effective in
      treatment of locoregionally advanced nasopharyngeal carcinoma (NPC). However, the
      prognostic factors after CCRT have not been evaluated. We therefore attempt to
      evaluate factors that influence treatment outcomes following CCRT. METHODS AND
      MATERIALS: Seventy-four (5 in stage III and 69 in stage IV) patients with
      locoregionally advanced NPC were treated with CCRT. Radiotherapy was delivered
      either at 2 Gray (Gy) per fraction per day up to 70 Gy or 1.2 Gy, 2 fractions per
      day, up to 74.4 Gy. Concurrent chemotherapy consisted of cisplatin and 5
      fluorouracil. Cox proportional-hazards model was used to analyze the prognostic
      factors which included age, gender, pathologic type, T, N, lactate dehydrogenase
      (LDH), and infiltration of the clivus. RESULTS: The primary tumor control rate at
      3 years was 96.7% (95% confidence interval [CI]: 92.5-100), distant metastasis
      free survival 81.1% (95% CI: 70.6-91.6), disease-free survival 77.0% (95% CI:
      65.3-88.7), and overall survival 79.8% (95% CI: 69.2-90.4) with a median follow
      up interval of 29 months (range 15-74 months). Cox proportional-hazards model
      revealed that infiltration of the clivus and serum level of LDH before treatment
      were the most two important factors that predict distant metastases. Infiltration
      of the clivus and the serum LDH level greater than 410 U/L were strongly
      associated with distant metastasis-free survival (p = 0.0004 and p = 0.0002,
      respectively). When these two risk factors were considered together, no distant
      metastasis was observed in 40 patients with both intact clivus and LDH < or = 410
      U/L. On the contrary, 13 of the remaining 34 patients with at least one risk
      factor developed distant metastasis (p = 0.0001). CONCLUSION: Our study
      demonstrates that CCRT can improve the primary tumor control of 96.7% and disease
      free survival of 77.0% at 3-year follow-up. Distant metastasis, however, is the
      major cause of failure. Infiltration of the clivus by the tumor and LDH greater
      than 410 U/L are the two independent and useful prognostic factors in patients
      with locoregionally advanced NPC who were treated with CCRT. Good- and poor-risk
      patients can be distinguished by virtue of their having both conditions.

PMID- 9652836
TI  - Factors affecting mandibular complications in low dose rate brachytherapy for
      oral tongue carcinoma with special reference to spacer.
AB  - PURPOSE: To evaluate the efficacy of a spacer in the prevention of mandibular
      complications in low dose rate (LDR) brachytherapy (BRT) for oral tongue
      carcinoma. METHODS AND MATERIALS: A retrospective analysis was conducted using
      103 patients with T1 or T2 tongue carcinoma treated by a single plane
      implantation of iridium (192Ir) pins between 1979-1994. Of these patients, 60
      were treated by BRT alone, and the rest were combined with external irradiation
      (Ext) and/or chemotherapy (CHT). Forty-eight and 55 patients were given BRT with
      and without a spacer, respectively. Spacers were individually made of acrylic
      resin according to a prosthetic technique so as to obtain the thickness of 7-10
      mm at the lingual part of the implanted side. Variables, including a spacer,
      which may be associated with the development of osteoradionecrosis (ORN) of the
      mandible, were analyzed by the Cox proportional hazards regression analysis.
      RESULTS: Our spacer reduced about 50% of the absorbed dose at the lingual side
      surface of the lower gingiva (LSG) to that in the absence of a spacer. Absolute
      incidence of ORN was 2.1% (1 of 48) and 40.0% (22 of 55), with and without a
      spacer, respectively, and the difference was statistically significant by
      univariate analysis (p = 0.0004). It was revealed by the Cox analysis that the
      spacer (p = 0.0247), combined CHT (p = 0.0295), and combined Ext (p = 0.0279)
      were significant independent factors associated with the development of ORN. The
      spacer was shown to be a significant factor by univariate analysis (p = 0.0037),
      but not by multivariate analysis when analysis was restricted to the patients who
      did not receive CHT. The absorbed dose, dose rate, and biological effective dose
      (BED) reflecting early or late response were estimated at the LSG, and
      prognosticators associated with the incidence of ORN were also determined by the
      Cox analysis. Particularly, BED for late response by BRT, the total absorbed
      dose, and any BED by Ext plus BRT were highly significant factors in the whole
      population. Essentially similar results were obtained in the patients without
      receiving CHT. CONCLUSIONS: It was clarified that our spacer effectively prevents
      mandibular complications in LDR BRT by 192Ir for oral tongue carcinoma.
      Furthermore, introduction of a spacer provided novel information concerning the
      development of ORN, where BED particularly for late response given by BRT, the
      total absorbed dose, and any BED by Ext plus BRT could be good prognostic factors
      only when estimated at the LSG.

PMID- 9652837
TI  - Conformal radiotherapy of Stage III non-small cell lung cancer: a class solution
      involving non-coplanar intensity-modulated beams.
AB  - PURPOSE: We developed a semiautomatic class solution to irradiate centrally
      located Stage III non-small cell lung cancer (NSCLC), involving a beam intensity
      modulation technique and optimization using a biophysical cost function. METHODS
      AND MATERIALS: Treatment for 10 patients with Stage III NSCLC was planned, using
      a conventional three- or four-beam three-dimensional (3D) technique and two
      techniques involving, respectively, seven (BIM1) and five (BIM2) noncoplanar beam
      incidences with intensity modulation. Two planning target volumes were defined:
      PTV1 included macroscopic tumor volume and PTV2 included macroscopic and
      microscopic disease. Beams were divided into beam parts (segments) and their
      outlines were defined during virtual simulation. Optimization using a biophysical
      cost function determined beam weights, segment weights, and wedge angles.
      Biological end points included tumor control probability of both target volumes
      (TCP1 and TCP2) and normal tissue complication probability (NTCP) of heart, lung,
      and spinal cord. The resulting uncomplicated local control probability (UCLP) was
      calculated. Physical end points included dose at PTV1 expressed as a dose minimum
      and dose maximum. Target-dose inhomogeneity was constrained in all plans.
      RESULTS: Concerning tumor evaluation, TCP1 was 74% (range 54-89%) for the 3D
      plan, 78.0% (range 62-94%) for BIM1, and 86.0% (range 59-93%) for BIM2. TCP1*TCP2
      was, respectively, 67.0% (range 39-81%), 73.0% (range 56-94%), and 81.0% (range
      54-93%). Minimum doses to PTV1 were 85, 80, and 88 Gy with the three respective
      techniques, while dose maxima were 89, 101, and 100 Gy. NTCPs of lung were 45.0%
      (range 11-75%) for 3D, 19.5% (range 8-59%) for BIM1, and 24.5% (range 3-61%) for
      BIM2. NTCPs of heart and spinal cord were comparable for all techniques. ULCPs
      were 37.0% (range 9-73%), 52.5% (range 22-86%), and 60.0% (range 20-85%),
      respectively. Applying physical limits to ensure clinical safety, minimum doses
      at PTV1 were recalculated. These were 72, 71, and 74 Gy for 3D, BIM1, and BIM2,
      respectively. CONCLUSION: The BIM2 plan is a candidate class solution for dose
      escalation studies in centrally located Stage III NSCLC.

PMID- 9652838
TI  - Results of treating primary tumors of the trachea with radiotherapy.
AB  - PURPOSE: To report the efficacy of treatment and to identify prognostic factors
      that were predictive of survival in primary tumors of the trachea treated with
      radiotherapy. METHODS AND MATERIALS: The medical records of patients treated at
      the Peter MacCallum Cancer Institute in the period 1962 to 1995 were reviewed.
      Forty-two patients were eligible for the study and were treated with
      radiotherapy. Squamous cell carcinoma (SCC) was the commonest subtype and
      patients generally presented with long-standing respiratory symptoms. Eleven
      patients were planned for treatment with at least 50 Gy to the primary, while the
      rest were treated with lower doses. RESULTS: The estimated median survival for
      all patients was 5.7 months, with 13% surviving at 2 years. Univariate analysis
      revealed performance status, weight loss, and lymph node or distant metastatic
      involvement as significant prognostic factors. Patients planned for treatment
      with at least 50 Gy survived longer than patients treated with less than 50 Gy,
      but this was probably due to selection of patients with better prognostic factors
      for higher dose treatment.

PMID- 9652839
TI  - Study of lung density corrections in a clinical trial (RTOG 88-08). Radiation
      Therapy Oncology Group.
AB  - PURPOSE: To investigate the effect of lung density corrections on the dose
      delivered to lung cancer radiotherapy patients in a multi-institutional clinical
      trial, and to determine whether commonly available density-correction algorithms
      are sufficient to improve the accuracy and precision of dose calculation in the
      clinical trials setting. METHODS AND MATERIALS: A benchmark problem was designed
      (and a corresponding phantom fabricated) to test density-correction algorithms
      under standard conditions for photon beams ranging from 60Co to 24 MV. Point
      doses and isodose distributions submitted for a Phase III trial in regionally
      advanced, unresectable non-small-cell lung cancer (Radiation Therapy Oncology
      Group 88-08) were calculated with and without density correction. Tumor doses
      were analyzed for 322 patients and 1236 separate fields. RESULTS: For the
      benchmark problem studied here, the overall correction factor for a four-field
      treatment varied significantly with energy, ranging from 1.14 (60Co) to 1.05 (24
      MV) for measured doses, or 1.17 (60Co) to 1.05 (24 MV) for doses calculated by
      conventional density-correction algorithms. For the patient data, overall
      correction factors (calculated) ranged from 0.95 to 1.28, with a mean of 1.05 and
      distributional standard deviation of 0.05. The largest corrections were for
      lateral fields, with a mean correction factor of 1.11 and standard deviation of
      0.08. CONCLUSIONS: Lung inhomogeneities can lead to significant variations in
      delivered dose between patients treated in a clinical trial. Existing density
      correction algorithms are accurate enough to significantly reduce these
      variations.

PMID- 9652840
TI  - Efficacy of total lymphoid irradiation for chronic allograft rejection following
      bilateral lung transplantation.
AB  - PURPOSE: To assess the safety and efficacy of total lymphoid irradiation (TLI) in
      patients experiencing chronic rejection following bilateral lung transplantation
      (BLT). PATIENTS AND MATERIALS: Eleven patients received TLI for chronic allograft
      rejection (bronchiolitis obliterans syndrome) refractory to conventional
      treatment modalities. Radiation therapy (RT) was prescribed as 8 Gy delivered in
      10 0.8-Gy fractions, 2 fractions/week, via mantle, paraaortic, and inverted-Y
      fields. Serial pre- and post-RT pulmonary function values, complete blood counts,
      and immunosuppressive augmentation requirements [use of methylprednisolone,
      murine anti-human mature T-cell monoclonal antibody (OKT3), polyclonal
      antithymocyte globulin (ATG), and tacrolimus] were monitored. RESULTS: In the 3
      months preceding TLI, the average decrease in forced expiratory volume in 1 s
      (FEV1) was 34% (range 0-75%) and the median number of immunosuppression
      augmentations was 3 (range 0-5). Only 4 of 11 patients completed all 10 TLI
      treatment fractions. Reasons for discontinuation included progressive pulmonary
      decline (four patients), worsening pulmonary infection (two patients), and
      persistent thrombocytopenia (one patient). Seven of the 11 patients failed within
      8 weeks of treatment cessation. One patient had unabated rejection and received
      bilateral living related-donor transplants; he is alive and well. Six patients
      died. Two of these deaths were due to pulmonary infection from organisms isolated
      prior to the start of RT; the other four deaths were from progressive pulmonary
      decline. The four remaining patients had durable positive responses to TLI (mean
      follow-up of 47 weeks; range 24-72). Comparing the 3 months preceding RT to the 3
      months following treatment, these four patients had improvements in average FEV1
      (40% decline vs. 1% improvement) and fewer median number of immunosuppressive
      augmentations (3.5 vs. 0). None of these patients has developed
      lymphoproliferative disease or has died. Features suggestive of a positive
      response to TLI included longer interval from transplant to RT, higher FEV1 at
      initiation of RT, and absence of preexisting pulmonary infection. CONCLUSION:
      Total lymphoid irradiation for chronic allograft rejection refractory to
      conventional medical management following BLT was tolerable. A subset of patients
      experienced durable preservation of pulmonary function and decreased
      immunosuppressive requirements. Patients with rapidly progressive allograft
      rejection, low FEV1, or preexisting infection were least likely to benefit from
      irradiation. Early initiation of TLI for patients experiencing chronic allograft
      rejection following BLT may be warranted.

PMID- 9652841
TI  - Local and distant recurrence after conservative management of "very low-risk"
      breast cancer are dependent events: a 10-year follow-up.
AB  - PURPOSE: To determine the risk factors associated with recurrence after breast
      conserving treatments, and the relationship between occurrence of a local
      recurrence and subsequent distant metastases. METHODS AND MATERIALS: Among the
      3697 patients with primary breast cancer treated at Institut Paoli-Calmettes
      Cancer Center, Marseille, between 1980 and 1995, we retrospectively analyzed 756
      patients who had been treated with conservative surgery with uninvolved margins
      of excision, were node-negative, and had received uniform radiotherapy and no
      chemotherapy. One third of the patients received hormonal therapy via tamoxifen
      or surgical castration. The endpoints considered were local failures and distant
      metastases. All tumors were reviewed by our pathologists. The median follow-up
      for the 700 survivors was 62 months. RESULTS: In the multivariate analysis,
      histological multifocality (p = 0.0076), peritumoral vessel invasion (p =
      0.0215), and young age (p = 0.0245) were associated with an increased risk of
      local recurrences, whereas tumor size (p = 0.0013), young age (p = 0.003), and
      histological multifocality (p = 0.0414) were associated with an increased risk of
      distant metastases. Local recurrences and distant metastases had similar yearly
      event probabilities. Median time to distant metastases was shorter after a local
      recurrence. Early timing of local recurrences did not mark a higher risk of
      distant metastases. Hazard of relapsing from distant metastases was 4.4 times
      higher after a local recurrence. CONCLUSION: our results support the hypothesis
      that, in this subset of patients, local recurrences favor further dissemination
      of cancer cells. We are unable to clearly identify a group who would benefit from
      more aggressive local therapy.

PMID- 9652842
TI  - Thallium-201 perfusion scintigraphy in the evaluation of late myocardial damage
      in left-side breast cancer treated with adjuvant radiotherapy.
AB  - PURPOSE: To evaluate late myocardial damage after adjuvant radiotherapy using a
      mixed-beam (photons plus electrons) technique to treat the internal mammary lymph
      nodes in left-side breast cancer. METHODS AND MATERIALS: A bicycle ergometer
      stress test coupled with thallium-201 perfusion scintigraphy and analysis by
      single-photon computed tomography (CT) was performed on 19 patients treated with
      left-side breast/chest wall and internal mammary radiation for breast cancer
      between 1987 and 1993. To be sure that we would evaluate late toxicity caused by
      the irradiation, patients had to fulfill the following eligibility criteria: left
      side breast cancer, treatment between 1987 and 1993 and no recurrence during
      follow-up, age < or = 75 years, no known risk for coronary artery disease, no
      previous chemotherapy, internal mammary field treated with an association of
      photons and electrons, and CT scan-based treatment planning. RESULTS: Median age
      at scintigraphy was 59 years. Two patients did not reach optimal exercise level
      and were not evaluable. Among the 17 evaluable patients representing 91.6 patient
      years of follow-up, there were no perfusion defects by visual or quantitative
      analysis. CONCLUSION: The mixed-beam technique seemed to spare the heart from
      harmful irradiation and to protect the myocardium. Results need to be confirmed
      on the long-term use of this technique.

PMID- 9652843
TI  - Twice-daily fractionation of external irradiation with brachytherapy and
      chemotherapy in carcinoma of the cervix with positive para-aortic lymph nodes:
      Phase II study of the Radiation Therapy Oncology Group 92-10.
AB  - PURPOSE: The purpose of this study was to evaluate the toxicity and efficacy of
      twice-daily external irradiation to the pelvis and para-aortics with
      brachytherapy and concurrent chemotherapy for carcinoma of the cervix with
      positive para-aortic lymph nodes. METHODS AND MATERIALS: This study was designed
      to administer twice-daily radiation doses of 1.2 Gy to the pelvis and para
      aortics at 4- to 6-h intervals, 5 days per week. The total external radiation
      doses were 24 to 48 Gy to the whole pelvis, 12 to 36 Gy parametrial boost, and 48
      Gy to the para-aortics with an additional boost to a total dose of 54 to 58 Gy to
      the known metastatic para-aortic site. One or two intracavitary applications were
      performed to deliver a total minimum dose of 85 Gy to point A. Cisplatin (75
      mg/m2, days 1 and 22) and 5-FU (1000 mg/m2/24 h x 4 days; days 1 and 22) were
      given for two or three cycles. RESULTS: Twenty-nine patients with clinical Stages
      I to IV carcinoma of the cervix with biopsy-proven para-aortic lymph nodes were
      enrolled in this study. Hyperfractionated external radiotherapy was completed in
      86% (25 of 29). Brachytherapy was given in two applications to 48% (14 of 29),
      31% (9 of 29) had one intracavitary application, 14% (4 of 29) had no
      brachytherapy, one had three applications, and one had five HDR applications.
      Radiotherapy was completed per protocol in 69%. Three courses of chemotherapy
      were given to 24% (7 of 29), 72% (21 of 29) received two courses, and one patient
      did not receive chemotherapy. The acute toxicity from chemotherapy was Grade 1 in
      3%, Grade 2 in 17%, Grade 3 in 48%, and Grade 4 in 28%. Radiotherapy toxicity was
      Grade 1 in 7%, Grade 2 in 34%, Grade 3 in 21%, and Grade 4 in 28%. One Grade 5
      toxicity occurred and the patient died from a myocardial infarction from
      chemotherapy and radiotherapy colitis during her course of therapy. The median
      follow-up time was 18.9 months. The overall survival estimates were 59% at 1 year
      and 47% at 2 years. The probability of local-regional failure was 38% at 1 year
      and 49% at 2 years. The probability of disease failure at any site was 45% at 1
      year and 59% at 2 years. CONCLUSION: The results suggest that twice-daily
      external irradiation to the pelvis and para-aortics with brachytherapy and
      concurrent chemotherapy resulted in an unacceptably high rate (31%, 9 of 29) of
      Grade 4 nonhematologic toxicity. One patient died from complications of therapy.
      Radiotherapy was completed per protocol in 69%. The survival estimates appear no
      better than standard fractionation radiotherapy without chemotherapy. Additional
      follow-up is necessary for long-term survival estimates.

PMID- 9652844
TI  - The prognostic significance of pre- and posttreatment SCC levels in patients with
      squamous cell carcinoma of the cervix treated by radiotherapy.
AB  - PURPOSE: To investigate the prognostic significance of the pre- and posttreatment
      serum squamous cell carcinoma antigen (SCC) levels in patients with Stage I-IVA
      squamous cell carcinoma of the cervix primarily treated by radiotherapy.
      MATERIALS AND METHODS: 401 patients with squamous cell carcinoma of cervix
      primarily treated with radiotherapy (RT) were included in this study. All had
      preRT, and 249 patients had postRT serum SCC values. The association of
      pretreatment SCC level with the clinical parameters, including stage, hemoglobin
      (Hb) level, age, cell differentiation, and lymph node status, was assessed by
      univariate and multivariate analysis. The prognostic significance of pretreatment
      SCC level and these clinical parameters were evaluated. The impact of postRT
      residual induration and SCC levels on survival was analyzed. RESULTS: 1. PreRT
      SCC level strongly correlated with stage. After controlling for stage, only SCC
      levels higher than 10 ng/ml were associated with enlarged lymph nodes shown in CT
      scan. No association of preRT SCC level with other clinical parameters was found.
      2. SCC level higher than 10 ng/ml, but not between 2-10 ng/ml, had significant
      impact on survival in a multivariate analysis. Stage, Hb levels (<10 g/dl) and
      positive lymph node shown by CT scan were also independent prognostic factors for
      survival. No significant difference in failure pattern in terms of local and/or
      distant sites was found in patients with different SCC levels. 3. Patients with
      residual induration and/or persistently elevated SCC level at 2-3 months after RT
      had a significantly higher incidence of treatment failure. Persistently elevated
      SCC level is a stronger predictor for treatment failure than residual induration
      by pelvic examination, and is associated with a higher incidence of distant
      metastasis. One third of patients with initial SCC level higher than 10 ng/ml had
      persistently elevated SCC. CONCLUSION: Pretreatment SCC levels higher than 10
      ng/ml are an independent predictor for poor prognosis in patients included in
      this study, and can be used as one of the prognostic factors for selection of
      patients for intensive treatment. Persistently elevated SCC levels after RT is a
      strong predictor for treatment failure. A combination of clinical pelvic
      examination and SCC levels provides useful information for the need of further
      work-up and management.

PMID- 9652845
TI  - Interstitial radiation for recurrent cervix or endometrial cancer in the
      suburethral region.
AB  - Recurrent tumors in the suburethral area are uncommon, but potentially morbid
      lesions. Brachytherapy, with or without external beam irradiation, was used to
      treat 10 consecutive women with lesions ranging from 1-6 cm in the suburethral
      area. All women achieved local control, with one woman developing a serious
      complication. Four of the 10 women remain alive without evidence of disease. A
      high rate of distant metastasis in those women who have recurred despite previous
      adjuvant pelvic radiation following hysterectomy for endometrial cancer should
      prompt the investigation of effective systemic chemotherapeutic agents.

PMID- 9652846
TI  - Sensory and motor dysfunction assessed by anorectal manometry in uterine cervical
      carcinoma patients with radiation-induced late rectal complication.
AB  - PURPOSE: To investigate the effects of radiation on anorectal function in
      patients with carcinoma of the uterine cervix. METHODS AND MATERIALS: Anorectal
      manometry was carried out on 24 patients (complication group) with late radiation
      proctitis. All of the manometric data from these patients were compared with
      those from 24 age-matched female volunteers (control group), in whom radiation
      treatment had not yet been performed. RESULTS: Regardless of the severity of
      proctitis symptoms, 25% of patients demonstrated all their manometric data within
      the normal range, but 75% of patients exhibited one or more abnormal manometric
      parameters for sensory or motor functions. Six patients (25%) had an isolated
      sensory dysfunction, eight patients (33.3%) had an isolated motor dysfunction,
      and four patients (16.7%) had combined disturbances of both sensory and motor
      functions. The maximum tolerable volume, the minimal threshold volume, and the
      urgent volume in the complication group were significantly reduced compared with
      those in the control group. The mean squeeze pressure in the complication group
      was significantly reduced, whereas the mean resting pressure and anal sphincter
      length were unchanged. CONCLUSIONS: Physiologic changes of the anorectum in
      patients with late radiation proctitis seem to be caused by a variety of sensory
      and/or motor dysfunctions in which many different mechanisms are working
      together. The reduced rectal reservoir capacity and impaired sensory functions
      were crucial factors for functional disorder in such patients. In addition,
      radiation damage to the external anal sphincter muscle was considered to be an
      important cause of motor dysfunction.

PMID- 9652847
TI  - Effect of filgrastim (G-CSF) during chemotherapy and abdomino-pelvic radiation
      therapy in patients with ovarian carcinoma.
AB  - PURPOSE: To evaluate the safety and effectiveness of filgrastim (granulocyte
      colony-stimulating factor, G-CSF) in reducing neutropenia and treatment
      interruptions during whole abdominal radiotherapy for ovarian cancer. METHODS AND
      MATERIALS: Sixteen patients with ovarian cancer treated with 2 to 6 courses of
      cisplatin-containing chemotherapy and abdomino-pelvic radiation therapy received
      filgrastim for neutrophil counts <2 x 10(9)/L. Endpoints for analysis included
      the ability to maintain the neutrophil count in the target range, number of
      treatment interruptions due to neutropenia, and toxicity attributed to
      filgrastim. RESULTS: Fourteen patients received a mean of 2.9 courses of
      filgrastim (each with a mean duration of 4.1 days), with no treatment
      interruptions due to neutropenia. The majority of neutrophil counts were
      maintained above the target range of 2 x 10(9)/L during treatment.
      Thrombocytopenia requiring treatment interruption was seen in six patients and
      necessitated platelet transfusions in one. Thrombocytopenia occurred at a mean
      abdominal radiation dose of 2207 cGy and in all but one patient was preceded by
      one or more episodes of neutropenia. In comparison with a control group of 31
      patients treated without filgrastim there was no reduction in treatment
      interruptions. Four patients did not complete treatment because of persistent
      thrombocytopenia yet received a mean of 94% of the planned abdominal radiation
      dose and 69% of the planned pelvic dose. Filgrastim toxicity was limited to mild
      skeletal pains in six patients and a Grade 1 skin rash in two patients.
      CONCLUSIONS: Filgrastim is safe and effective in preventing neutropenia and
      reducing neutropenic treatment interruptions during abdominal radiotherapy in
      patients with ovarian cancer. However, there was no clear benefit to the use of
      filgrastim as thrombocytopenia became the dose-limiting toxicity resulting in a
      risk of treatment interruptions and early termination of radiotherapy.

PMID- 9652848
TI  - Clinical results of 24 pituitary macroadenomas with linac-based stereotactic
      radiosurgery.
AB  - PURPOSE: To determine the impact of stereotactic radiosurgery (SRS) on the
      clinical course, hormonal status, and follow-up CT/MRI scan of pituitary
      macroadenomas. METHODS AND MATERIALS: From July 1988 to March 1996, 24 pituitary
      macroadenomas had been treated using 6 MV linear accelerator based SRS. They
      consisted of 11 (45.8%) prolactinomas, 2 (8.3%) growth hormone (GH)-secreting
      tumors, 1 (4.2%) Cushing's disease, 8 (33.3%) nonsecreting (nonfunctioning: NF)
      tumors, and 2 (8.3%) mixed prolactin-growth hormone (PRL-GH)-secreting tumors
      (M:F = 12:12; aged 21-61 years). Postoperative irradiation was performed in all
      cases except for the instance of Cushing's disease. The prescribed dose to tumor
      center varied from 10 to 27 Gy (mean 21.1 Gy) using a collimator size of 0.5 to
      2.5 cm. The follow-up duration ranged from 13 to 89 months (mean 49.2 months).
      Results from these patients were compared to our results using conventional
      radiation. RESULTS: Visual acuity and field defect were improved or became normal
      in 19 (79.2%) cases. Four (16.7%) remained unchanged after the treatment. One
      (4.1%) progressed 6 years after SRS and subsequently had repeat surgery with
      conventional boost irradiation. Of the 13 (46.4%) prolactinomas, including two
      mixed PRL-GH secreting tumors, 11 (84.1%) revealed normal hormonal levels within
      1 year after SRS. In contrast, it took 2 years to become normal after
      conventional radiation therapy. In four GH-secreting tumors including two mixed
      PRL-GH secreting tumors, SRS and conventional methods showed similar responses.
      On follow-up imagings of the 21 patients, the mass was completely resolved in 4
      (16.7%), including 3 PRLs and one NF, decreased in 11 (45.8%), and unchanged in 5
      (16.7%) with central necrosis or cysts. One (4.2%) progressed and was reoperated
      6 years after treatment. The complications related to SRS were comparable to
      those from conventional method. CONCLUSION: Radiosurgery can be used effectively
      in patients with pituitary adenoma. In this study, a more rapid hormonal and
      clinical response was achieved with radiosurgery than with conventional pituitary
      irradiation treatment.

PMID- 9652849
TI  - Single-fraction stereotactic radiotherapy: a dose-response analysis of
      arteriovenous malformation obliteration.
AB  - PURPOSE: Stereotactic radiotherapy delivered in a high-dose single fraction is an
      effective technique to obliterate intracranial arteriovenous malformations (AVM).
      To attempt to analyze the relationships between dose, volume, and obliteration
      rates, we studied a group of patients treated using single-isocenter treatment
      plans. METHODS AND MATERIALS: From May 1986 to December 1989, 100 consecutive
      patients with angiographically proven AVM had stereotactic radiotherapy delivered
      as a high-dose single fraction using a single-isocenter technique. Distribution
      according to Spetzler-Martin grade was as follows: 79 grade 1-3, three grade 4, 0
      grade 5, and 18 grade 6. The target volume was spheroid in 74 cases, ellipsoid in
      11, and large and irregular in 15. The targeted volume of the nidus was estimated
      using two-dimensional stereotactic angiographic data and, calculated as an ovoid
      shaped lesion, was 1900 +/- 230 mm3 (median 968 mm3; range 62-11, 250 mm3). The
      mean minimum target dose (Dmin) was 19 +/- 0.6 Gy (median 20 Gy; range: 3-31.5).
      The mean volume within the isodose which corresponded to the minimum target dose
      was 2500 +/- 300 mm3 (median 1200 mm3; range 75-14 900 mm3). The mean maximum
      dose (Dmax) was 34.5 +/- 0.5 Gy (median 35 Gy; range 15-45). The mean
      angiographic follow-up was 42 +/- 2.3 months (median 37.5; range 7-117). RESULTS:
      The absolute obliteration rate was 51%. The 5-year actuarial obliteration rate
      was 62.5 +/- 7%. After univariate analysis, AVM obliteration was influenced by
      previous surgery (p = 0.0007), Dmin by steps of 5 Gy (p = 0.005), targeted volume
      of the nidus (< or = 968 mm3 vs. >968 mm3; p = 0.015), and grade according to
      Spetzler-Martin (grade 1-3 vs. grade 4-6; p = 0.011). After multivariate
      analysis, the independent factors influencing AVM obliteration were the Dmin
      [relative risk (RR) 1.9; 95% confidence interval (CI) 1.4-2.5; p < 0.0001] and
      grade distribution according to Spetzler-Martin (RR 1.4; 95% CI 1.1-1.7; p =
      0.010). Delayed complications were observed in eight patients. The 5-year
      actuarial rate of delayed complications was 7.4%. CONCLUSION: After stereotactic
      radiotherapy delivered in a single high dose using a single-isocenter technique,
      the success rate for complete obliteration is independently correlated to Dmin
      but does not seem to be influenced by Dmax and the targeted volume of the nidus.

PMID- 9652850
TI  - Induction chemotherapy and radiotherapy in loco-regionally advanced epidermoid
      carcinoma of the anal canal.
AB  - PURPOSE: To evaluate the efficacy of induction chemotherapy in combination with
      radiotherapy for treatment of loco-regionally advanced epidermoid anal carcinoma.
      METHODS AND MATERIALS: Thirty-one patients diagnosed during the period 1989-1994
      with loco-regionally advanced cancer of the anal canal (phiTmax > or = 4 cm or T4
      or N+) were treated with induction chemotherapy consisting of one to three
      courses of carboplatin (300-375 mg/m2 i.v.) and 5-fluorouracil [5,000 mg/(m2 x
      120 h) i.v.] followed by external beam irradiation +/- surgery. RESULTS: The
      toxicity of the chemotherapy was low. Twenty-nine patients were tumor free after
      the primary therapy. Kaplan-Meier analyses were made for overall survival, tumor
      specific survival, freedom from recurrence, preservation of sphincter, and event
      free survival. For these end points the 5-year data were 67, 85, 80, 69, and 51%,
      respectively. CONCLUSION: The results are promising but a well-designed
      randomized trial is needed to further elucidate the role of induction
      chemotherapy in the treatment of loco-regionally advanced anal carcinoma.

PMID- 9652851
TI  - In vitro radiosensitization of human cervical carcinoma cells by combined use of
      13-cis-retinoic acid and interferon-alpha2a.
AB  - BACKGROUND: Significant antitumor activity has been reported with the combined
      use of 13-cis-retinoic acid (cRA) and interferon-alpha2a (IFN-alpha) in the
      treatment of advanced-stage cervical cancers and skin cancers. Since IFN-alpha
      has been shown to be a modest radiation enhancer for selected malignant tumor
      cells and the cytotoxic activity is more enhanced by combining cRA and IFN-alpha,
      we hypothesized that the exposure of selected human carcinoma cells to combined
      cRA and IFN-alpha would render the cells highly radiosensitive. METHODS AND
      MATERIALS: Two human cervical carcinoma cell lines, ME-180 and HeLa-S3, were
      chosen for the present study because of the different characteristics of the
      retinoic acid receptor status of the cell lines. To demonstrate the effects of
      combined cRA and IFN-alpha treatment on radiation response, we exposed the cells
      to cRA, IFN-alpha, or a combination of the drugs for 72 h before radiation.
      Experiments were carried out at minimally cytotoxic concentrations of the drug
      for radiation studies. End points of the study were cell growth inhibition and
      clonogenic ability of the single-plated cells. Effects of cRA and IFN-alpha on
      radiation response were quantitatively analyzed by constructing the radiation
      cell survival curves of ME-180 and HeLa cells. RESULTS: ME-180 cells exhibited
      varying degrees of cytotoxicity with cRA and IFN-alpha, while HeLa cells showed
      no toxic effects with the same treatment. Combined treatment of cRA and IFN-alpha
      produced an additive cytotoxic effect in ME-180 cells. Radiosensitization was
      minimal when ME-180 cells were treated with either cRA or IFN-alpha before
      radiation. When ME-180 cells were exposed to 10 microM cRA for 48 h and 1000 U/ml
      IFN-alpha for 24 h prior to radiation, there was a significant enhancement in
      radiation-induced cell killing; the dose modification factor was 2.1 +/- 0.9 at
      the 1% cell-survival level. On the other hand, HeLa-S3 cells exhibited no
      increased cytotoxicity or radiation enhancement under the same experimental
      conditions. CONCLUSION: The present data provide a radiobiological basis for
      using cRA and IFN-alpha as a combination radiosensitizer in selected human
      carcinoma cells.

PMID- 9652852
TI  - Radiosensitizing potential of gemcitabine (2',2'-difluoro-2'-deoxycytidine)
      within the cell cycle in vitro.
AB  - PURPOSE: Gemcitabine (2',2'-difluorodeoxycytidine; dFdCyd) is a new deoxycitidine
      analog which exhibits substantial activity against solid tumors and
      radiosensitizing properties in vitro. To examine cell cycle-specific effects of a
      combined treatment with gemcitabine and radiation, the in vitro clonogenic
      survival of two different cell lines was measured for cells from log-phase
      culture, G1 and S-phase cells. METHODS AND MATERIALS: Chinese hamster (V79) and
      human colon carcinoma (Widr) cells were exposed to different radiation doses and
      for different points of time relative to gemcitabine treatment (2 h). Experiments
      were also carried out with different cell-cycle populations obtained after
      mitotic selection (V79) or after serum stimulation of plateau-phase cells (Widr).
      The resulting survival curves were analyzed according to the LQ model, and mean
      inactivation doses (MID) and the cell cycle-specific enhancement ratios (ER) were
      calculated from the survival curve parameters. RESULTS: Effectiveness of combined
      treatment of log-phase cells was greatest when cells were irradiated at the end
      of the gemcitabine exposure [ER: 1.28 (V79), 1.24 (Widr)]. For later times after
      the removal of the drug, radiosensitization declined, approaching independent
      toxicity. From the time course of interactive-type damage decay half-life values
      of 75 min (V79) and 92 min (Widr) were derived. Gemcitabine did not
      radiosensitize G1 Widr cells or V79 cells from the G1/S border, but substantial
      radiosensitization was observed for the S-phase cell preparations [ER: 1.45 (V79
      lateS), 1.57 (Widr)]. CONCLUSIONS: Treatment of cells with gemcitabine
      immediately before irradiation eliminates, or at least greatly reduces, the
      variation in radiosensitivity during the cell cycle that is manifested by
      radioresistance during S phase. This reversal of S-phase radioresistance could
      imply that gemcitabine interferes with the potentially lethal damage
      repair/fixation pathway. Other approaches have been taken to overcome S-phase
      radioresistance, such as hyperthermia or densely ionizing radiation, and combined
      treatments with dFdCyd could prove of value to complement such efforts.

PMID- 9652853
TI  - Selective in vivo radiosensitization by 5-fluorocytosine of human colorectal
      carcinoma cells transduced with the E. coli cytosine deaminase (CD) gene.
AB  - PURPOSE: The E. coli cytosine deaminase (CD) gene encodes an enzyme capable of
      converting the nontoxic prodrug 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU),
      a known radiosensitizer. Having previously shown that combined CD suicide gene
      therapy and radiation (RT) results in pronounced radiosensitization in vitro, we
      progressed to in vivo studies of combined therapy. METHODS AND MATERIALS: WiDr
      human colon cancer cells were transduced in vitro with the CD gene and cells
      expressing CD were selected for use as xenografts in a nude mouse model. After
      administration of 5-FC, tumors received 10-30 Gy local field radiation (RT) and
      tumor growth delay was compared to control animals receiving either 5-FU, 5-FC,
      or RT alone. RESULTS: Maximal growth delay was seen in mice treated with 5-FC for
      6 consecutive days prior to RT. Combined treatment with 15 Gy radiation resulted
      in a dose-modifying factor (DMF) of 1.50, and a greater DMF was observed with
      higher doses of radiation. There was no appreciable toxicity using this new
      approach. In contrast, a similar treatment of combined 5-FU and radiation
      resulted in considerable toxicity and no appreciable radiosensitization.
      CONCLUSION: The present results show that combined suicide gene therapy and RT
      results in pronounced antitumor effect without any notable toxicity. This
      indicates that the CD gene may be useful in the development of novel treatment
      strategies combining radiation and gene therapy in the treatment of locally
      advanced cancers.

PMID- 9652854
TI  - Murine strain differences in the volume effect and incidence of radiation-induced
      colorectal obstruction.
AB  - PURPOSE: Interindividual variation in the level of normal tissue damage after
      radiotherapy has been clinically observed. Murine models have suggested that
      there may be a genetic component to the variation in susceptibility of different
      radiation-induced normal tissue complications. Currently, there are no
      experimental data available describing interstrain differences in the "volume
      effect" for irradiated normal tissues, such as the colorectum. The aims of this
      study are to determine if there are strain differences in: 1. the incidence of
      colorectal obstruction; and 2. the volume effect, after irradiation of the
      colorectum using two mouse strains that are known to vary in their susceptibility
      for developing pulmonary fibrosis. METHODS AND MATERIALS: Various lengths (5.2 to
      22.9 mm) of the colorectum of male C57B1/6 and C3Hf/Kam mice were irradiated with
      a single dose (30 Gy) of 137Cs gamma rays. Also, various doses (20 to 35 Gy) were
      given to a single length (22.9 mm) of colorectum. The incidence of obstruction
      was determined as a function of length and dose at 6 months after irradiation.
      The Threshold Probability model was fit to the length-response data. RESULTS:
      C57B1/6 mice developed colorectal obstruction at significantly higher incidence
      than C3Hf/Kam mice at all lengths after a single dose of 30 Gy. In addition, the
      data showed a strain difference in the threshold length of colorectum that had to
      be irradiated before obstructions were observed. CONCLUSION: Strain differences
      in the incidence of radiation-induced colorectal obstruction were observed,
      consistent with previous studies that showed a strain difference in radiation
      induced pulmonary fibrosis. The presence of a threshold length of colorectum that
      was different for the two strains is consistent with the concept that there may
      be a critical threshold amount of colorectal tissue that can tolerate a high dose
      without complication, and that the dimensions of the threshold may vary among
      individuals.

PMID- 9652855
TI  - Increased induction of Ca2+-mediated differentiation by gamma ray is mediated by
      endogenous activation of the protein kinase C signaling pathways in mouse
      epidermal cells.
AB  - PURPOSE: The aim of this study was to determine whether gamma-rays can affect
      Ca2+-induced differentiation in normal and neoplastic mouse epidermal cells.
      METHODS AND MATERIALS: After gamma-ray irradiation, primary and v-rasHa
      transformed mouse keratinocytes were cultured for 48 h in 0.12 mM Ca2+-containing
      media, and cellular translocation from cytosolic to particulated fraction of each
      PKC isozyme and expressions of differentiation markers were examined. RESULTS:
      Morphological difference was seen at 48 h after irradiation in both Ca2+-shifted
      normal and v-rasHa transformed cells; v-rasHa cells were more resistant to the
      radiation than normal cells. Radiation potentiated granular cell-differentiation
      marker expressions (filaggrin, loricrin, and SPR-1) in both normal and v-rasHa
      transformed cells. In the case of spinous cell markers, the expression of
      keratins K1 and K10, which are usually blocked in v-rasHa cells was increased
      after irradiation. However, there was no change of K8 expression level, which can
      be seen only after v-rasHa transfection. Cellular fractionation and immunoblot
      analysis with antibodies against PKCalpha, delta, epsilon, eta, and xi revealed
      that PKCalpha was responsible for the differentiation marker expression.
      CONCLUSIONS: These findings suggest that PKCalpha is an important component of
      the signaling pathway regulating radiation-induced differentiation in both normal
      and neoplastic epidermal cells.

PMID- 9652856
TI  - Effects of radiation on endothelial function.
AB  - PURPOSE: The response of endothelium to ionizing radiation was studied. METHODS
      AND MATERIALS: The abdominal aorta in different experimental groups of rats was
      irradiated, and the response of arterial rings from the irradiated segments to
      norepinephrine, acetylcholine (ACh), and nitroglycerin (NTG) was studied.
      Nonirradiated thoracic segments in the same experimental animals were used as as
      a control for comparisons. Two age-matched nonirradiated control groups were also
      studied. RESULTS: A poor endothelium-dependent vasodilator response was obtained
      with ACh in the irradiated rings and also in those not directly irradiated; the
      endothelium-independent vasodilator response to NTG was preserved during the
      first 3 days after irradiation. By 6 months, both the endothelium-dependent
      response and endothelium-independent response were impaired. CONCLUSIONS:
      Alterations in nitric oxide synthesis and/or release by the endothelium were
      observed during the early phase of radiation in irradiated and nonirradiated
      segments. In the delayed phase of radiation, endothelium-independent muscular
      relaxation was also affected.

PMID- 9652857
TI  - Suppression of heat-induced HSF activation by CDDP in human glioblastoma cells.
AB  - PURPOSE: The kinetics of the accumulation of inducible 72-kD heat shock protein
      (hsp72) and the activation of heat shock transcriptional factor (HSF) after
      hyperthermia and/or CDDP treatment in two human glioblastoma cell lines, A-172
      having the wild-type p53 gene and T98G having the mutated p53 gene were
      evaluated. METHODS AND MATERIALS: Western blot analysis of hsp72, gel-mobility
      shift assay of HSF, cell survival, and development of thermotolerance were
      examined. RESULTS: The prominent suppression of heat-induced hsp72 accumulation
      by CDDP was seen in A-172 cells, but not in T98G cells. This was due to the p53
      dependent inhibition of heat-induced HSF activation by CDDP. The interactive
      hyperthermic enhancement of CDDP cytotoxicity was observed in A-172 cells, but
      not in T98G cells. In addition, the heat-induced thermotolerance was suppressed
      by the presence of CDDP in the pretreatment. CONCLUSION: Suppression of heat
      induced hsp72 accumulation by CDDP contributes to an interactive hyperthermic
      enhancement of CDDP cytotoxicity in the cells bearing the wild-type p53 gene.

PMID- 9652858
TI  - Centralized multiinstitutional postimplant analysis for interstitial prostate
      brachytherapy.
AB  - PURPOSE: To investigate the feasibility and utility of performing centralized
      postimplant analysis for transperineal interstitial permanent prostate
      brachytherapy (TIPPB) by conducting a pilot study that compares the results
      obtained from 125I implants conducted at five different institutions. METHODS AND
      MATERIALS: Dose-volume histogram (DVH) analysis was performed on 10 postimplant
      CT scans from each of five institutions. This analysis included the total
      implanted activity of 125I, ultrasound, and CT volumes of the prostate, target
      volume ratios, dose homogeneity quantifiers, prostate dose coverage indices, and
      rectal doses. As a result of the uncertainty associated with the delineation of
      the prostatic boundaries on a CT scan, the contours were redrawn by a single,
      study center physician, and a repeat DVH analysis was performed. This provided
      the basis for comparison between institutions in terms of implant technique and
      quality. RESULTS: By comparing total activity to preimplant ultrasound volume we
      clearly demonstrated that differences exist in implant technique among these five
      institutions. The difficulty associated with determining glandular boundaries on
      CT scans was apparent, based upon the variability in prostate volumes drawn by
      the various investigators compared to those drawn by the study center physician.
      This made no difference, of course, in the TVR or homogeneity quantifiers that
      are independent of target location. Furthermore, this variability made
      surprisingly little difference in terms of dose coverage of the prostate gland.
      Rectal doses varied between institutions according to the various implant
      techniques. CONCLUSIONS: Centralized, outcome-based evaluation of transperineal
      interstitial permanent prostate brachytherapy is viable and appropriate. Such an
      approach could be reasonably used in the conduct of multiinstitutional trials
      used to study the efficacy of the procedure.

PMID- 9652859
TI  - Clinical variability of target volume description in conformal radiotherapy
      planning.
AB  - PURPOSE: The pivotal step in radiation planning is delineation of the target
      volume and production of a treatment plan to encompass this. This study assesses
      the variation of physicians in creation of these volumes. METHODS AND MATERIALS:
      Three radiologists and eight radiation oncologists outlined the gross tumour
      volume (GTV) on the planning CT scans of four cases with T3 bladder cancer. In
      addition, the radiation oncologists (RO) created a planning target volume
      according to a set protocol for all cases. Volumes were produced and comparison
      of these volumes and the position of the isocenters were analysed. In addition,
      the margins allowed were measured and compared. RESULTS: There was a maximum
      variation ratio (largest to smallest volume outlined) of the GTV in the four
      cases of 1.74 among radiologists and 3.74 among oncologists. There was a
      significant difference (p = 0.01) in mean GTV between RO and the radiologists.
      The mean GTV of the RO exceeded the radiologists by a factor of 1.29 with a mean
      difference of 13.4 cm3. The variation ratio in PTV among oncologists ranged from
      1.25 to 3.33. There was no significant difference in mean PTV values between the
      two groups of ROs divided by specialization in uro-oncology. The mean variation
      in location of the isocenter from the centroid of the radiologists' volume in the
      four cases was from 2.6 to 5.7 mm. There was, however, a wide range of values
      from 1.4 mm to 24.1 mm. Median margin per case ranged from 14.7 to 18.7 mm.
      Minimum margins allowed in each case varied from minus 7 mm to 9 mm. CONCLUSION:
      This study demonstrates significant interphysician variability in producing
      target volumes and radiation plans for conformal radiotherapy. The scale of this
      difference is clearly of significance, with up to 3-fold variation in volumes
      delineated by clinicians. The factors leading to these differences will be
      further addressed. The existence of such variability, however, clearly needs to
      be accepted as a factor in the overall uncertainty analysis in conformal
      radiotherapy planning.

PMID- 9652860
TI  - A commercial IMRT treatment-planning dose-calculation algorithm.
AB  - PURPOSE: The dose-calculation algorithm for a commercial arc-based intensity
      modulated radiation therapy (IMRT) treatment-planning and delivery system
      (Peacock, NOMOS Corporation) is described. METHODS AND MATERIALS: The IMRT
      delivery system uses a dynamically controlled multileaf collimator with 40 leaves
      that project on our accelerator to either 1.0 x 0.84 cm2 or 1.0 x 1.68 cm2 at
      isocenter arranged in two banks of 20 leaves each. The dose-calculation algorithm
      uses tissue-phantom ratios derived from percent depth dose measurements, measured
      relative output data, and single leaf profiles. Some compromises are made in the
      algorithm terms to enable more straightforward dosimetry measurements and to
      reduce dose computation times. The dose calculation algorithm is presented, and
      consequences of the approximations are investigated using previously published 4
      MV photon beam data. RESULTS: Most of the approximations lead to dose errors of a
      few percent. However, the use of depth-invariant single-leaf profiles results in
      errors as large as 9% for 4 MV fixed beams. CONCLUSIONS: Large dosimetric errors
      are possible for small fixed fields using this algorithm. However, the algorithm
      is designed for tomotherapy dose delivery, where doses are delivered from
      multiple directions and depths. Investigations of the algorithm in more
      clinically relevant conditions have been conducted and show that the algorithm
      accuracy is 1.3% and therefore is clinically acceptable for tomotherapy.

PMID- 9652861
TI  - Improvement of CT-based treatment-planning models of abdominal targets using
      static exhale imaging.
AB  - PURPOSE: CT-based models of the patient that do not account for the motion of
      ventilation may not accurately predict the shape and position of critical
      abdominal structures. Respiratory gating technology for imaging and treatment is
      not yet widely available. The purpose of the current study is to explore an
      intermediate step to improve the veracity of the patient model and reduce the
      treated volume by acquiring the CT data with the patients holding their breath at
      normal exhale. METHODS AND MATERIALS: The ventilatory time courses of diaphragm
      movement for 15 patients (with no special breathing instructions) were measured
      using digitized movies from the fluoroscope during simulation. A subsequent
      clinical protocol was developed for treatment based on exhale CT models. CT scans
      (typically 3.5-mm slice thickness) were acquired at normal exhale using a spiral
      scanner. The scan volume was divided into two to three segments, to allow the
      patient to breathe in between. Margins were placed about intrahepatic target
      volumes based on the ventilatory excursion inferior to the target, and on only
      the reproducibility of exhale position superior to the target. RESULTS: The
      average patient's diaphragm remained within 25% of the range of ventilatory
      excursion from the average exhale position for 42% of the typical breathing
      cycle, and within 25% of the range from the average inhale position for 15% of
      the cycle. The reproducibility of exhale position over multiple breathing cycles
      was 0.9 mm (2sigma), as opposed to 2.6 mm for inhale. Combining the variation of
      exhale position and the uncertainty in diaphragm position from CT slices led to
      typical margins of 10 mm superior to the target, and 19 mm inferior to the
      target, compared to margins of 19 mm in both directions under our prior protocol
      of margins based on free-breathing CT studies. For a typical intrahepatic target,
      these smaller volumes resulted in a 3.6% reduction in Veff for the liver.
      Analysis of portal films shows proper target coverage for patients treated based
      on exhale modeled plans. CONCLUSIONS: Modeling abdominal treatments at exhale,
      while not realizing all the gains of gated treatments, provides an immediate
      reduction in the volume of normal tissue treated, and improved reliability of
      patient data for NTCP modeling, when compared to current "free breathing" CT
      models of patients.

PMID- 9652862
TI  - A little to a lot or a lot to a little: is NTCP always minimized in multiport
      therapy?
AB  - PURPOSE: We address the question of whether or not, for the same average (or
      integral) dose, a smaller uniform dose to an entire normal tissue structure
      always results in a lower normal tissue complication probability (NTCP) than does
      a proportionally larger dose to a partial volume of the same structure. METHODS
      AND MATERIALS: A recent compilation of NTCP data and two theoretical formulations
      of the dependence of NTCP on dose and partial volume irradiated-the Lyman probit
      equation and the binomial model-are used to examine this question. Both models
      fit equally well available NTCP data. RESULTS: Empirical data indicate that for
      lung, kidney, and possibly liver (but not for esophagus, brain, or heart), given
      a fixed tumor dose and fixed integral dose, NTCP can be minimized by irradiating
      a partial volume fraction rather than the entire normal organ. The binomial model
      supports this interpretation, whereas the probit model predicts that for all
      organs uniform irradiation of the whole organ always results in the lowest
      possible NTCP. CONCLUSIONS: In contrast to what is commonly believed, this study
      suggests that for at least two normal tissues, namely lung and kidney, there may
      be situations where "a lot to a little" (i.e., fewer treatment ports) will result
      in higher tumor control probability and better treatment plan than "a little to a
      lot" (i.e., multifield treatment). This finding, which is independent of the
      binomial or probit models used here, depends only on the accuracy of the
      empirical NTCP data. It is also interesting to note that: a) lung and kidney are
      commonly classified as parallel tissues, while the others have more of a serial
      architecture; and b) the choice of the NTCP model can have a profound impact on
      treatment planning decisions.

PMID- 9652863
TI  - A simple method to verify in vivo the accuracy of target coordinates in linear
      accelerator radiosurgery.
AB  - PURPOSE: A simple method that verifies the coincidence of the isocenter with the
      center of the target volume in radiosurgery treatment conditions is described.
      The accuracy is compared to that of accepted computerized procedures employing
      fiducial markers. METHODS AND MATERIALS: The center of the beam is identified by
      a cylindrical localizer, fixed to the plate of the supplemental collimator, with
      a 2 x 50 mm tungsten rod coincident with the beam axis and is projected onto the
      x-ray portal verification films. Prior to irradiation, the coordinates of the
      intersection of the beams axes, which is in a known spatial relationship with the
      isocenter, are read directly on portal x-ray films and their coincidence with the
      coordinates set during patient positioning, is checked. RESULTS: The mean
      displacement in AP, Lat, and Vert coordinates respectively, over 84 patients,
      between the coordinates calculated by the computerized procedure employing
      fiducial markers and the coordinates calculated by using the rulers was 0.3 +/-
      0.4 mm. CONCLUSIONS: From the results obtained with the two methods we can
      conclude that rulers method can be used as a fast indirect control of the
      position of the radiation isocenter. Moreover, the dimensions of the radiation
      field and the correct alignment of the tertiary circular collimator can be also
      documented.

PMID- 9652864
TI  - Optimal image resolution for digital storage of radiotherapy-planning images.
AB  - PURPOSE: To evaluate the quality of digitized radiation-planning images at
      different resolution and to determine the optimal resolution for digital storage.
      METHODS AND MATERIALS: Twenty-five planning films were scanned and digitized
      using a film scanner at a resolution of 72 dots per inch (dpi) with 8-bit depth.
      The resolution of scanned images was reduced to 48, 36, 24, and 18 dpi using
      computer software. Image qualities of these five images (72, 48, 36, 24, and 18
      dpi) were evaluated and given scores (4 = excellent; 3 = good; 2 = fair; and 1 =
      poor) by three radiation oncologists. An image data compression algorithm by the
      Joint Photographic Experts Group (JPEG) (not reversible and some information will
      be lost) was also evaluated. RESULTS: The scores of digitized images with 72, 48,
      36, 24, and 17 dpi resolution were 3.8 +/- 0.3, 3.5 +/- 0.3, 3.3 +/- 0.5, 2.7 +/-
      0.5, and 1.6 +/- 0.3, respectively. The quality of 36-dpi images were definitely
      worse compared to 72-dpi images, but were good enough as planning films.
      Digitized planning images with 72- and 36-dpi resolution requires about 800 and
      200 KBytes, respectively. The JPEG compression algorithm produces little
      degradation in 36-dpi images at compression ratios of 5:1. CONCLUSION: The
      quality of digitized images with 36-dpi resolution was good enough as radiation
      planning images and required 200 KBytes/image.

PMID- 9652865
TI  - Monte Carlo-based dose-rate tables for the Amersham CDCS.J and 3M model 6500
      137Cs tubes.
AB  - PURPOSE: (1) To present reference-quality dose-rate distributions for the
      Amersham CDCS.J-type 137Cs intracavitary source (hitherto unavailable in the
      literature) and updated tables for the 3M model 6500/6D6C source. (2) To assess
      the accuracy of the widely used 1D pathlength (Sievert integral) algorithm for
      lightly filtered 137Cs tube sources. METHODS AND MATERIALS: A Monte Carlo photon
      transport code is used to calculate the dose-rate distributions about the 3M
      source and the CDCS.J source based on radiographic examination of the sources and
      the vendors' specifications. Dose-rate distributions are provided in the form of
      Cartesian "away-and-along" lookup tables. Using a general form of the Sievert
      integral, calculated dose-rate distributions were compared to the Monte Carlo
      benchmark calculations treating the filtration coefficients as best-fit
      parameters as well as approximating them by linear energy absorption
      coefficients. In addition, the errors introduced by approximating the active
      source core by uniform cylinders or line sources was evaluated. RESULTS: The
      Model CDCS.J dose distribution differs from that of the 3M model 6500 source by 
      5.9% to +14.4% (root-mean-square [RMS] average: 2.6%). The RMS accuracy of the
      Sievert algorithm is 2.4% to 2.8% (error range of -1.4% to 7.6%) when filtration
      coefficients for steel and ceramic media are approximated by linear energy
      absorption coefficients. If the filtration coefficients are treated as parameters
      of best fit, selected to minimize the discrepancies between 1D pathlength and
      Monte Carlo calculations, the RMS error is reduced to 0.8% (error range of -1.8%
      to 4.1%). The optimal values of stainless steel and low-density ceramic or glass
      filtration coefficients are approximately independent of the source geometry.
      CONCLUSIONS: The widely used Sievert integral algorithm accurately characterizes
      the dose distribution around stainless-steel clad low-density matrix 137Cs
      sources, particularly if design-independent best-fit values of the filtration
      coefficients are used. Although both families of source designs studied produce
      similar dose distributions, source-design specific dose distributions should be
      used for clinical treatment planning and dose-algorithm validation.

PMID- 9652866
TI  - Regarding cardiac function and morbidity in long-term survivors of Hodgkin's
      disease.

PMID- 9652867
TI  - Should we be using confidence intervals when reporting results of oncology
      studies?

PMID- 9652868
TI  - Regarding predicting radiation response.

PMID- 9652869
TI  - Regarding Zagars and Pollack.

PMID- 9652870
TI  - Predicting lung function after irradiation for lung cancer: comment on paper by
      Marks et al.

PMID- 9652871
TI  - Is the safety and efficacy of calcium antagonists now established?

PMID- 9652872
TI  - Nifedipine after acute myocardial infarction--sola dosis facit venenum: only the
      dose determines the harm.

PMID- 9652873
TI  - The inappropriate use of hypothesis testing to infer safety of calcium channel
      blockers.

PMID- 9652874
TI  - Calcium channel blockers and the risk of cancer: a preclinical assessment.
AB  - The preclinical evidence for a potential influence of calcium channel blockers
      (CCBs) on carcinogenesis is discussed in the light of a broad database from
      rodent carcinogenicity studies as well as literature data. In all bioassays
      performed in rats and mice on the dihydropyridine CCBs--nifedipine, nimodipine,
      nisoldipine, and nitrendipine--no evidence was found for a carcinogenic potential
      of these compounds. Calcium is an essential intracellular signal for cell
      proliferation and apoptosis. The crucial role of increased cell proliferation in
      all stages of carcinogenesis is well documented. Some indirect experimental
      evidence also points to a role of defective apoptosis in tumor promotion. CCBs
      uniformly inhibit cell proliferation, whereas the influence of CCBs on apoptosis
      is inconsistent, resulting in an inhibition or increase in apoptosis dependent on
      cell type. Accordingly, antitumorigenic effects of CCBs have been reported based
      on their antiproliferative action. A tumor-promoting effect of CCBs based on
      inhibition of apoptosis, however, remains purely speculative and, in fact, can be
      denied based on the results of in vivo bioassays. It is therefore concluded that
      there is no preclinical evidence that should give rise to concern over the
      carcinogenic potential of dihydropyridine-type CCBs.

PMID- 9652875
TI  - Long-term mortality follow-up of hospital survivors of a myocardial infarction
      randomized to nifedipine in the SPRINT study. Secondary Prevention Reinfarction
      Israeli Nifedipine Trial.
AB  - This study was intended to determine the 5-year mortality of 2138 post-myocardial
      infarction (MI) patients who took part in the Secondary Prevention Reinfarction
      Israeli Nifedipine Trial (SPRINT). In the framework of the SPRINT study, 1065
      patients were randomly assigned 30 mg/d nifedipine therapy, for a mean 10-month
      follow-up period, and 1073 received placebo. No information is available
      concerning treatment after the first year. One-year postdischarge mortality was
      5.0% in the placebo group and 5.9% among patients receiving nifedipine (P =
      0.37). Mortality rates after 5 years of follow-up in patients previously
      randomized to 1 year of nifedipine therapy and placebo were 18.4% and 18.3%,
      respectively. The 5-year mortality risk ratio associated with randomization to
      nifedipine over 1 year, adjusted for age, gender, past MI, angina, diabetes,
      hypertension, MI location, and therapy, was 1.00 (95% CI: 0.81-1.22). Our results
      do not support an association between nifedipine therapy and a late harmful
      effect on long-term mortality.

PMID- 9652876
TI  - Nifedipine and cancer mortality: ten-year follow-up of 2607 patients after acute
      myocardial infarction.
AB  - Recent publications contended that the use of short-acting calcium antagonists
      may double the risk of cancer incidence and possibly increase mortality in
      hypertensive patients. The purpose of this study was to assess the risk ratio for
      cancer mortality associated with nifedipine in a large population of patients
      post-myocardial infarction. Cancer mortality data, over a 10-year period, were
      obtained on 2607 hospital survivors of acute myocardial infarction who were
      screened, but not included, in the Secondary Prevention Reinfarction Israeli
      Nifedipine Trial (SPRINT I) study. In this group of patients, 526 (20%) were on
      nifedipine, according to their treating physicians' decision. In the cohort of
      screened patients not included in SPRINT I, there were 22 (4.2%) cancer-related
      deaths in the patients on nifedipine compared with 114 (5.5%) in the group not
      treated with nifedipine (P = 0.23). In multivariate analysis, the 10-year cancer
      mortality risk ratio associated with nifedipine therapy was 1.06 (95% CI 0.52
      2.18). The current analysis shows no evidence of an increased risk of cancer
      mortality in a large number of patients treated at baseline with nifedipine.

PMID- 9652877
TI  - Acute myocardial infarction mortality related to use of calcium antagonists
      before admission to hospital.
AB  - We investigated whether prior use of calcium antagonists in 80 (16.8%) out of 477
      patients (64% males) admitted with acute myocardial infarction (MI) had any
      impact on in-hospital mortality. Patients using calcium antagonists were slightly
      older (74 years vs. 72 years, 2P = 0.039) than those not taking them and fewer
      were male patients. Previous MI, diabetes mellitus, and prior use of aspirin,
      beta-blockers, and long-acting nitrates were more frequent in patients on calcium
      antagonists. In contrast, fewer patients on calcium antagonists prior to symptoms
      received thrombolytic treatment (21.3% vs. 34.8%, 2P = 0.018). The study had an
      observational exposed/nonexposed design, and we looked for both crude and
      adjusted effects. Of the 83 patients (17.4%) who died during hospitalization, 18
      patients were in the calcium antagonist group (22.5%). The odds ratio (OR) for
      these patients to die in the hospital was 1.48 and the 95% confidence interval
      (CI) 0.78-2.78; 2P = 0.19. When adjusting for confounders (gender, age, smoking
      habit, previous MI, and diabetes mellitus, as well as prior use of aspirin, beta
      blockers, long-acting nitrates, and thrombolytic treatment at entry) OR was 1.08
      and 95% CI 0.57-2.05; 2P = 0.85. Thus, we found no excess in-hospital mortality
      in patients with acute MI using calcium antagonists prior to the onset of
      symptoms.

PMID- 9652878
TI  - Adverse reactions to antihypertensive therapy.
AB  - A large number of antihypertensive agents are available today. They belong to
      different drug classes and permit the treating physician to choose the drug he
      deems best suited for the treatment of an individual patient. Because
      hypertension is usually asymptomatic yet requires long-term therapy,
      consideration of potential undesirable effects of drugs used for its treatment is
      important for making the appropriate choice. In this context, a precise
      understanding of the typical adverse reaction profiles of the different drugs is
      essential. This article provides a short review of the adverse reaction profiles
      of the main classes of antihypertensive drugs and refers to topics such as the
      recent controversy regarding calcium channel blockers and comparative
      investigations between different antihypertensive agents. Furthermore, the
      effects of antihypertensives on metabolic parameters, differences between their
      effects in subgroups of patients and in patients with different concomitant
      diseases, and the potential of antihypertensives for interactions with other
      drugs are briefly discussed. Even with a good knowledge of all of these aspects,
      however, no fixed plan for drug treatment of hypertension suitable for every
      patient can be established. A high percentage of adverse drug reactions can,
      however, be avoided by appropriate drug selection and dosage, carried out after
      careful consideration of the known adverse reaction profiles as well as the known
      spectrum of pharmacological actions of the different compounds. Low doses are
      often effective and well tolerated. Instead of increasing the dose, it is usually
      preferable to add a low dose of a second agent with a different mode of action if
      one drug given alone does not sufficiently lower blood pressure. This procedure
      avoids many adverse drug reactions attributable to an exaggerated pharmacological
      response, and, if chosen carefully, this combination may also reduce
      counterregulatory reactions secondary to the fall in blood pressure.

PMID- 9652879
TI  - Selection of drug therapy in stable angina pectoris.
AB  - Drug therapy in stable angina has two aims: the prevention of major cardiac
      events (such as unstable angina, myocardial infarction, or death) and the control
      of chest pain and transient myocardial ischemia. Given the low incidence of major
      cardiac events in patients with stable angina, primary preventive studies are
      scarce because they require a large sample size and long-term follow-up. Thus
      far, only aspirin and some lipid-lowering agents have been shown to be effective
      for this purpose. Antiischemic drugs reduce the imbalance between myocardial
      oxygen demand and supply, either by reducing oxygen consumption or by increasing
      coronary blood flow. The ideal approach would be to target drug therapy against
      the ischemia-inducing factor in each patient. The characteristics of anginal
      symptoms do not seem to help in selecting medical therapy, whereas a standard
      exercise test and a provocative test of coronary vasoconstriction may provide
      useful information in order to select patients who will preferentially respond to
      either a beta-blocker or a calcium antagonist. The combination of two or more
      anti-ischemic drugs does not seem to be any more effective than an adequately
      titrated monotherapy in reducing the occurrence of myocardial ischemia in
      individual patients. Combination therapy in stable coronary artery disease should
      include an individually selected and optimally titrated anti-ischemic agent and
      aspirin, with the addition of a lipid-lowering agent in patients with even mild
      hypercholesterolemia.

PMID- 9652880
TI  - Safety, tolerability, and neurohormonal changes of the combination captopril plus
      losartan in the early postinfarction period: a pilot study.
AB  - Suppression of formation of angiotensin II (A-II) is thought to be a major
      contributor to the hemodynamic response to angiotensin-converting enzyme
      inhibition (ACE-in) therapy. However, angiotensin II (A-II) plasma levels may
      rebound during ACE-in treatment. The study sought to verify the feasibility,
      safety, and tolerability of the combination of captopril (75 mg/d) plus losartan
      (25 mg/d). We also wished to establish whether the combination was able to avoid
      the increase of angiotensin II resulting from losartan treatment in early
      postinfarction phases of reperfused anterior acute myocardial infarction (AMI).
      Forty-four patients, hospitalized for suspected anterior AMI within 4 hours from
      the onset of symptoms, suitable for thrombolysis (first episode), Killip class I
      II and reperfused, receiving 75 mg/d of captopril within 3 days from admission,
      and with systolic blood pressure (BP) >120 mmHg were randomized (single-blind)
      into two groups: Group A included 22 patients (6 women and 16 men) and received
      captopril 75 mg/d and placebo. Group B included 22 patients (5 women and 17 men)
      and received captopril 75 mg/d within 3 days from admission plus losartan 12.5
      mg, as the first dose, and 25 mg/d (BP >110 mmHg) successively. Norepinephrine
      (NE) and A-II levels were measured on the 3rd and 10th days after admission. The
      two groups were similar with regard to age, sex, creatinine kinase peak, ejection
      fraction, end-systolic volume, and risk factors. Group B (captopril plus
      losartan) showed a significant reduction of BP, from 124 +/- 8.5 mmHg to 108 +/-
      6.4 mmHg, P < 0.001, at 10 days after admission. In group A, BP was 122 +/- 9
      mmHg, and 10 days after admission BP was 118 +/- 11 mmHg. NE and A-II values did
      not show significant differences in basal samples. At 10 days after admission
      values were NE 298 +/- 90 versus 272 +/- 86 pg/mL and A-II 6.07 +/- 2.97 versus
      5.29 +/- 2.05 pg/mL for the two groups. Our data suggest, for the first time,
      that the combination of captopril plus losartan is feasible and does not produce
      serious side effects. When losartan was added to ACE-in treatment, there was no
      significant increase in A-II.

PMID- 9652881
TI  - Increasing nitroglycerin release from patches enables circumvention of early
      nitrate tolerance.
AB  - Continuous treatment with transdermal nitroglycerin leads to tolerance
      development within the first day of application. Effective long-term therapy can
      be provided by interval treatment with nightly patch removal, but even during the
      hours of intermittent patch application there is rapid attenuation of initial
      effects. To assess whether an unattenuated antiischemic and antianginal efficacy
      during the hours of intermittent dosing can be maintained, a modified drug
      release profile with increasing plasma concentrations was evaluated using a
      double-blind, placebo-controlled crossover protocol. Eleven patients with
      documented coronary artery disease received, in a randomized order, a total of
      four low-dose nitroglycerin patches (5 mg/24 h each) or placebo, respectively, at
      intervals of 3 hours. After a treatment interval of 12 hours, all patches were
      removed for an equally long patch-free interval prior to renewed application of
      one patch the next morning. At a comparable workload, reductions of ST-segment
      depression of 65%, 63%, and 56% were found at 2.5 hours, 8 hours, and 12 hours
      after application of the first patch on day 1, respectively (all significant vs.
      placebo; 2.5 hours vs. 12 hours, n.s.). On day 2, the comparable reduction of 63%
      at 2.5 hours after renewed application indicates prevention of tolerance
      development during subchronic treatment. Effects on exercise capacity and angina
      pectoris paralleled those on exercise-induced ST-segment depression. Plasma
      concentrations of nitroglycerin increased from 223 pg/mL to 558 and 803 pg/mL on
      day 1 and amounted to 205 ng/mL at 2.5 hours on day 2. Thus, interval therapy
      with increasing nitroglycerin concentrations provides unattenuated antiischemic
      and antianginal efficacy during the hours of treatment and circumvention of early
      tolerance during subchronic application. This modified pharmacokinetic profile
      can be regarded as a model for an improved dosage regimen in nitrate interval
      therapy.

PMID- 9652882
TI  - Hip fracture prevention: a review.
AB  - The incidence of hip fractures worldwide is expected to almost quadruple in the
      next 60 years. Increased cost-containment pressures will focus attention not only
      on improvements in hip fracture treatment but also on prevention. Three
      approaches that can prevent hip fractures--preventing falls, preventing and
      treating bone fragility, and using external hip protectors--are reviewed.
      Although it is impossible to prevent all hip fractures, these methods may
      significantly reduce the annual incidence of these fractures.

PMID- 9652883
TI  - The short-term economic implications of prosthetic selection in hemiarthroplasty
      of the hip.
AB  - This retrospective study assessed the economic impact of prosthetic selection in
      the treatment of displaced intracapsular fractures. The records of 28 patients
      were divided into two groups: 16 patients who received an Austin-Moore,
      nonmodular device and 12 patients (6 men and 6 women; mean age, 77 years) who
      received a modular, bipolar device. The bipolar group had significantly greater
      mean operative times, total charges for the device, and total charges for
      supplies. Surgeons treating hip fractures should consider implant cost,
      functional outcome, and patient demands when selecting a prosthesis for
      hemiarthroplasty care.

PMID- 9652884
TI  - Is there a relationship between hypertension and lower-extremity contracture
      release in cerebral palsy?
AB  - Recent reports have suggested a relationship between release of lower-extremity
      contractures and the development of hypertension in cerebral palsy and
      poliomyelitis patients. A retrospective study was performed on 119 cerebral palsy
      patients who had undergone lower-extremity contracture releases. Temporary
      elevation of systolic blood pressure in the perioperative and intraoperative
      periods occurred in 46 patients (39%), and temporary elevation of diastolic blood
      pressure occurred in 14 patients (12%). Type of cerebral palsy, patient age,
      patient sex, type of anesthesia, and type of procedure were not significantly
      correlated with the temporary blood pressure elevations. No patient developed
      sustained elevation of systolic and diastolic blood pressure. We conclude that
      lower-extremity contracture release in pediatric patients is not associated with
      an increased incidence of postoperative hypertension.

PMID- 9652885
TI  - The quantitative anatomy of the superior gluteal artery and its location.
AB  - Twenty cadaveric posterior gluteal regions were dissected to quantitatively
      determine the location and dimensions of the superior gluteal artery and its
      branches on the posterior gluteal region. Two reference lines were defined: one
      (transverse) was drawn from the posterior inferior iliac spine (PIIS) across the
      ilium to the anterior superior iliac spine (ASIS), and another (vertical) was
      drawn orthogonal to the transverse line at a point 8 cm from the PIIS. Results
      showed that the average distances from the posterior superior iliac spine (PSIS)
      and PIIS to the superior gluteal artery origin at the sciatic notch were 60 mm
      and 42 mm, respectively. The deep superior branch traveled an average of 18 mm
      above the transverse line at the vertical line, and averaged 54 mm from the iliac
      crest at the same point. This same branch inserted in the medius an average of 29
      mm from the ASIS, and 11 mm above the transverse line, while providing 4 to 7
      perforators to the gluteus medius and 0 to 2 to the gluteus minimus. The deep
      inferior branch traveled an average of 23 mm below the transverse line along the
      vertical line and penetrated the minimus or medius 36 mm from the ASIS, while
      providing 3 to 8 perforators to the medius and 1 to 3 to the minimus. The average
      distance from the deep inferior branch to the superior edge of the acetabulum
      along the vertical line was 25 mm. These data may be helpful in preventing the
      injury of the superior gluteal artery during the posterior gluteal approach.

PMID- 9652886
TI  - Spinal ligament loading during axial distraction: a biomechanical model.
AB  - The objective of this study was to develop a method of measuring spinal ligament
      forces during axial distraction to understand the load-bearing contributions of
      the individual ligamentous structures in the lumbar spine. A sequential ligament
      cutting technique and the arthroscopically implantable force probe (AIFP,
      MicroStrain, Burlington, VT) were used to determine loading of the anterior
      longitudinal ligament (ALL), the posterior longitudinal ligament (PLL), and the
      remaining posterolateral complex (PLC) in an in vitro corpectomy model. During
      axial spinal distraction, the relative percentages of the total axial load in the
      individual structures were as follows: ALL, 37.5%; PLL, 17.2%; PLC, 45.3%.

PMID- 9652887
TI  - The effect of a cardiac rehabilitation program on the joints and spine:
      subjective evaluation.
AB  - To examine the effects of a cardiac rehabilitation exercise program on the joints
      of patients just recovered from a coronary disease episode, a questionnaire was
      distributed to such patients entering the program. Of 171 patients who completed
      the questionnaire, 76 indicated they had pain in some joints, most frequently in
      the back. Sixty-six patients were available to complete follow-up questions after
      participating in the exercise program for a minimum of 3 months. Pain, or lack
      thereof, remained unchanged in 35 participants. A decrease in pain was noted by
      27, and more pain by 4.

PMID- 9652888
TI  - Condensing osteitis of the clavicle: case report and review of the literature.
AB  - Osteitis condensans of the clavicle is a rare condition characterized by pain in
      the shoulder and often limitation of motion of the shoulder. The medical history
      and results of the physical examination, laboratory data, and radiographic
      studies (including computed tomography and magnetic resonance imaging), often
      establish the diagnosis. Patients who have slight or no pain usually require no
      treatment. Varying results have been reported for many different methods of
      treatment, including surgical excision, chemotherapy, antibiotics, nonsteroidal
      anti-inflammatory medications, radiation, local corticosteroid injection, and
      physical therapy. A typical case report and the differential diagnosis for
      condensing osteitis of the clavicle are presented.

PMID- 9652889
TI  - Aberrant position of the ulnar nerve and artery overlying the carpal canal.
AB  - Many anomalies of the ulnar nerve and artery within the wrist have been
      described. We report the first known case of the ulnar nerve and artery overlying
      the midportion of the transverse carpal canal, leaving Guyon's canal empty. This
      anomaly has considerable consequences for surgeons considering endoscopic carpal
      release, because the ulnar nerve and artery are at significant risk of injury.

PMID- 9652890
TI  - Synovitis secondary to giardiasis in children.
AB  - Giardia lamblia, a gastrointestinal protozoan, is one of the most common disease
      causing parasites in the world. Giardiasis is primarily encountered in areas with
      poor sanitation, but it is also seen in more developed countries. A possible
      sequela of Giardia infections of the bowel is reactive arthritis or synovitis.
      Few reports of synovitis secondary to giardiasis exist in the literature.
      Arthropathy secondary to giardiasis is uncommon, but may be underdiagnosed. In
      this study, Giardia synovitis was diagnosed in two children at a major children's
      hospital over a 20-year period. Both were boys, aged 7 years, 6 months and 1
      year, 8 months at the time of presentation. The knee was the affected joint in
      both patients, and both cases were initially misdiagnosed as septic arthritis.
      The synovitis subsided with treatment of the giardiasis, one with cefuroxime and
      the other with cefuroxime and metronidazole. The diagnosis of Giardia synovitis
      should be suspected by the presence of Giardia cysts in the stool, similar
      symptoms in other family members, a synovial white count under 40,000, and an
      increase in the eosinophil count. Although uncommon, giardiasis can cause severe
      synovitis that may be confused with a septic joint.

PMID- 9652891
TI  - Ultrasound for the diagnosis of retained splinters in the soft tissue of the
      hand.
AB  - Foreign material may present both a diagnostic and a surgical problem. Most
      irretrievable foreign bodies are wood and are radiolucent. Ultrasound offers an
      alternative way of preoperative imaging in these situations. We describe four
      cases of retained splinters in the hand that were localized with sonography and
      subsequently removed surgically. This report supports the reliability and
      efficiency of ultrasound as the primary imaging tool for the detection of foreign
      bodies if conventional radiographs are negative. Preoperative sonographic
      localization of the foreign body may be extremely useful to the surgeon and may
      minimize surgical dissection and operating room time.

PMID- 9652892
TI  - Midshaft femoral fracture, concomitant ipsilateral hip joint injury, and
      disruption of the knee extensor mechanism: a unique triad of dashboard injury.
AB  - Our experience with 10 patients who suffered midshaft fractures of the femur and
      injuries to their ipsilateral hips has resulted in a treatment protocol that we
      believe can avoid unnecessary complications. The surgical protocol is a three
      stage procedure based on (1) intramedullary nailing of the femur with
      interlocking for preserving the anatomic length and rotation of the femur; (2)
      treatment of the hip joint injury by means of open reduction and internal
      fixation of the acetabular fracture and/or reduction and fixation of the
      fractured femoral neck; and (3) repair of the extensor mechanism. Eight patients
      received this treatment and had fast recoveries. Union of the femoral fracture
      and full range of motion of the knee joint were observed within 3 months. In
      contrast, two patients who had received different surgical treatment had
      incomplete functional recoveries. This study offers a treatment protocol for
      ipsilateral disruption of the extensor mechanism, hip joint injury, and midshaft
      fracture of the femur in the multiply injured patient that can achieve full
      recovery with no complications. This relatively rare combination of injuries is
      definitely worthy of special attention.

PMID- 9652893
TI  - Entry point of reconstruction nail.
AB  - If the femoral neck is involved in a pathological process, the surgeon may avoid
      a base neck entry for the reconstructive nail. If a trochanteric entry is
      selected, the surgeon must be aware that the nail has to be driven more distally
      in order to place the neck screws properly. Violation of the knee joint is a
      consideration, and so is varus malposition.

PMID- 9652894
TI  - Errors in sex differentiation.

PMID- 9652895
TI  - Preferential use of branched-chain amino acids as an energy substrate in patients
      with liver cirrhosis.
AB  - We analyzed basal energy metabolism in 20 healthy volunteers and 41 cirrhotic
      patients by indirect calorimetry. Subjects were then given either glucose,
      branched-chain amino acids (BCAA) or fatty acids as an energy substrate. Resting
      energy expenditure (REE), nonprotein respiratory quotient (npRQ), and oxidation
      rates of glucose (% CHO), protein (% PRO) and fat (% FAT) were analyzed. REE and
      %FAT were significantly higher and % CHO and %PRO were significantly lower in
      cirrhosis than in controls. These changes correlated with disease severity.
      Glucose and BCAA were utilized efficiently as energy substrates and reduced %FAT
      in cirrhosis. Energy efficacy (increased energy expenditure/energy equivalent of
      the supplemented nutrient) was significantly higher in BCAA (96 +/- 16%) than in
      glucose (41 +/- 8%) (p<0.01) and fatty acids (27 +/- 13%) (p<0.05). Patients with
      cirrhosis have an increased energy requirement. BCAA seems to be the preferred
      substrate to meet this demand, because its energy efficacy is higher than glucose
      or fatty acids in cirrhosis.

PMID- 9652896
TI  - Eradication of Helicobacter pylori restores elevation of serum gastrin
      concentrations in patients with end-stage renal disease.
AB  - In order to explore the role of Helicobacter pylori (H. pylori) infection in
      hypergastrinemia in patients on dialysis, the changes in serum gastrin
      concentration were examined before and after eradication treatment for H. pylori.
      Twenty-seven patients on dialysis were treated for the eradication of H. pylori.
      Fasting serum gastrin concentrations were measured by a radioimmunoassay which
      detects gastrin 17. Ammonia and pH levels of the gastric juice were also
      measured. The serum gastrin concentrations were significantly decreased following
      eradication of H. pylori, and the mean value reached the normal range. The
      restoration of hypergastrinemia was associated with marked reductions of gastric
      juice ammonia and pH levels. In contrast, patients in whom H. pylori was not
      eradicated showed no changes in these parameters. In conclusion, the elevation of
      the fasting serum gastrin 17 concentration seen in dialysis patients appeared to
      be attributable to H. pylori infection in the stomach.

PMID- 9652897
TI  - Hereditary angioneurotic edema and thromboembolic diseases: I: How symptoms of
      acute attacks change with aging.
AB  - Localized edema of the larynx and pharynx leading to death from asphyxia has long
      been recognized as a characteristic symptom of hereditary angioneurotic edema
      (HANE). Long-term follow-up of younger HANE patients has revealed that transient
      localized acute attacks of edema affect tissues where the microcirculation
      maintains the blood supply. However, with aging, HANE attacks precipitate
      disseminated intravascular coagulation (DIC) or multiple organ failure (MOF).
      Substitution with a C1-inhibitor (C1-INH) has resulted in a fulminant lethal end
      with a rapid and profound decrease in antithrombin-III (AT-III) activity. A
      possible mechanism is as follows: Exogenous stimuli activate plasma proteinase
      systems with the generation of plasma kallikrein that activates the tissue factor
      pathway (TF) and liberates bradykinin (BK). In younger patients, BK enhances
      vascular permeability. In the elderly, activated TF is controlled by tissue
      factor pathway inhibitor (TFPI) and generates thrombin, which is the target
      enzyme of AT-III and precipitates DIC or MOF. In elderly patients, the
      characteristic symptom of HANE is hypercoagulation by age-related changes in the
      biosynthesis of AT-III or TFPI.

PMID- 9652898
TI  - Efficacy of a low-dose subcutaneous lisuride infusion in Parkinson's disease.
AB  - Five parkinsonian patients with motor fluctuations and dyskinesia after long-term
      treatment with levodopa were treated with subcutaneous lisuride infusion (0.24
      0.42 mg/day) together with oral levodopa for a mean period of 27 (range 13-36)
      months. All 5 patients showed marked initial improvement in mobility. Mild
      psychiatric side effects were observed in three patients; however, these side
      effects disappeared with reduction in the dosage of lisuride to 0.06 mg per day
      without a significant increase in motor fluctuations. A low dose of subcutaneous
      lisuride infusion with oral levodopa is an effective treatment for fluctuations
      of motor performance in parkinsonian patients without adverse psychiatric
      effects.

PMID- 9652899
TI  - Hepatic and splenic sarcoidosis evaluated by multiple imaging modalities.
AB  - We present a case of hepatosplenic sarcoidosis. A 51-year-old Japanese male, who
      was diagnosed to have sarcoidosis 4 years previously, was presented to our
      hospital because of dry cough and anorexia with weight loss. He had tender
      hepatosplenomegaly. A dynamic abdominal computed tomography (CT) revealed
      multiple small low-density areas in both liver and spleen, as well as in magnetic
      resonance imaging (MRI). The laparoscopic photographs showed many small whitish
      nodules surfacing on the liver and several tumorous nodules on the spleen.
      Multiple imaging modalities including dynamic CT and MRI are valuable for
      detecting focal hepatic and splenic lesions of sarcoidosis.

PMID- 9652900
TI  - Diabetes mellitus accompanied by nonocclusive colonic ischemia.
AB  - A 70-year-old man with diabetic triopathy was hospitalized with left lower
      quadrant abdominal pain and tenderness, muscle guarding and absent bowel sounds.
      Three hours after admission, creatine phosphokinase (CPK) was elevated and an
      abdominal plain film X-ray showed intestinal gas retention, indicating paralytic
      ileus due to inferior mesenteric artery occlusion. Urokinase (60,000 units/day)
      and heparin (10,000 units/day) were administered. Angiography showed no occlusion
      in the mesenteric artery. On the 16th day, the abdominal signs had disappeared
      and CPK was normalized. We diagnosed this case as nonocclusive colonic ischemia
      because of the hemorheological abnormalities due to diabetic triopathy and the
      hypercoagulable state.

PMID- 9652901
TI  - Apical hypertrophy with massive myocardial fibrosis: comparison with
      electrocardiographic changes.
AB  - We report the case of a 48-year-old woman with apical hypertrophy with massive
      myocardial fibrosis. She was admitted to our hospital because of general malaise.
      Echocardiographic examination showed asymmetrical apical hypertrophy, and an
      electrocardiogram showed a giant negative T wave on V3-V6. Right ventricular
      endomyocardial biopsy revealed massive myocardial fibrosis. Apical hypertrophy
      can lead to disorders that vary in severity, including rare massive myocardial
      fibrosis.

PMID- 9652902
TI  - Malignant lymphoma demonstrating sick sinus syndrome.
AB  - We report a case of T-cell-rich large B-cell lymphoma demonstrating sick sinus
      syndrome as a single initial symptom, followed by the retention of pericardial
      and pleural effusions. Intrapleural administration of interferon-alpha prevented
      reaccumulation of the pleural effusion for one and a half months, whereas
      systemic chemotherapy failed to control tumor growth in the skin and lymph nodes.
      The autopsy revealed involvement of the sinoatrial node of the heart by lymphoma
      cells.

PMID- 9652903
TI  - A rare case of 46,XX true hermaphroditism with hidden mosaicism with sex
      determining region Y chromosome-bearing cells in the gonads.
AB  - The sex-determining region Y chromosome (SRY) triggers testis determination. We
      report a 46,XX true hermaphrodite who had ambiguous genitalia at birth. A
      laparotomy at one year of age revealed this patient to have a testis on the right
      side and an ovotestis on the left side. By polymerase chain reaction analysis no
      SRY was detected in the DNA from the leukocytes but it was found in the DNA from
      the ovotestis. The hidden mosaicism with the Y-bearing cells in the gonads is
      likely the cause of the dual gonads in this patient.

PMID- 9652904
TI  - A hypopituitary patient who attained tall stature without growth hormone.
AB  - We describe an unusual patient with hypopituitarism who attained tall stature
      even without growth hormone (GH). A 37-year-old man was devoid of secondary
      sexual characteristics, but manifested tall stature with a eunuchoidal feature.
      Serum levels of GH, insulin-like growth factor-I, gonadotropins and testosterone
      were all below normal. GH secretion was not enhanced by any provocative stimulus.
      Adrenocorticotropic hormone increased after administration of corticotropin
      releasing hormone, but not after insulin-induced hypoglycemia. Thyrotropin
      increased in response to thyrotropin releasing hormone, but both free T3 and T4
      did not rise. Magnetic resonance imaging disclosed a transected pituitary stalk.
      The present patient had hypopituitarism due to perinatal problems but had grown
      with the aid of non-GH growth-promoting factors, which suggests that man may be
      able to achieve statural growth even without GH.

PMID- 9652905
TI  - Malignant insulinoma with extensive liver metastases presenting as disturbance of
      consciousness.
AB  - A 56-year-old man was referred to our hospital for evaluation of episodic
      disturbance of consciousness. Hypoglycemic symptoms were noted and Whipple's
      triad was satisfied. The 75 g OGTT and the glucagon test revealed a high baseline
      insulin level and hyperreactivity to glucagon. A pancreatic tumor and liver
      metastases were found by abdominal computed tomography (CT). Based on the finding
      of liver biopsy, the final diagnosis was malignant insulinoma with liver
      metastasis. He selected conservative treatment and no hypoglycemic crisis has
      occurred for one year since discharge. Early diagnosis and long-term follow-up is
      necessary since this tumor is slow growing.

PMID- 9652906
TI  - Multiple diffuse fibrosarcoma of bone associated with extramedullary
      hematopoiesis.
AB  - We report a case of multiple diffuse fibrosarcoma of bone. The patient, a 38-year
      old man, was referred to our hospital with knee pain, anemia and
      thrombocytopenia. No solid mass was seen on radiographic examination of the
      kneejoint, but magnetic resonance imaging showed hypointensity of the distal
      femur. Femoral biopsy revealed proliferation of long spindle-shaped fibrosarcoma
      cells, while a bone marrow biopsy of iliac bone (which appeared normal on
      radiographic examinations) showed replacement of hematopoietic cells by
      fibroblast-like spindle cells. A diagnosis of multiple diffuse fibrosarcoma of
      bone was therefore made. Autopsy revealed tumor invasion into multiple bones and
      several visceral organs and extramedullary hematopoiesis in the liver, spleen and
      lymph nodes. As this patient had leukoerythroblastic anemia with poikilocytosis,
      splenomegaly exhibiting extramedullary hematopoiesis, and apparent fibrotic
      change in his bone marrow, we suggest that this extremely rare disease should be
      considered in the differential diagnosis of myelofibrosis.

PMID- 9652907
TI  - Systemic mastocytosis with extensive polypoid lesions in the intestines;
      successful treatment with interferon-alpha.
AB  - A 35-year-old female presented in 1989 with hepatosplenomegaly, but no conclusive
      diagnosis was established. From 1992, she experienced transient episodes of
      facial flushing and palpitations. Osteosclerotic change was detected
      radiologically. Colonoscopy revealed massive polypoid lesions. Mast cells were
      demonstrated in bone marrow smear and imprinted preparations of colon biopsy
      specimens by toluidine blue staining. Plasma concentrations of histamine and
      soluble c-kit were elevated. She was successfully treated with interferon-alpha
      and prednisolone, resulting in the disappearance of histamine-related attacks and
      a gradual decrease in tumor size. However, the remission was interferon dose
      dependent. This case was considered as systemic mastocytosis with massive
      polypoid colon lesions and showed the importance of maintenance therapy with
      interferon-alpha.

PMID- 9652908
TI  - Double infection with Giardia lamblia and Salmonella paratyphi A associated with
      acute renal failure.
AB  - While traveling in India, a previously healthy twenty-year-old man had febrile
      diarrhea. The patient was prescribed medical therapy, and all symptoms were
      resolved. Fourteen days later, however, similar symptoms recurred. The patient
      was admitted to a local hospital, but was transferred to our department because
      of oliguria. Salmonella paratyphi A was isolated from blood and stool specimens,
      and Giardia lamblia was identified in his stool. The patient's condition was
      complicated by acute renal failure. The patient received tosufloxacin and
      metronidazole. Renal function recovered completely without hemodialysis.
      Paratyphoid fever and giardiasis were resolved. It is suggested that giardiasis
      exacerbated the paratyphoid fever.

PMID- 9652909
TI  - Na+, K+-ATPase inhibitor, ouabain accentuates irradiation damage in human tumour
      cell lines.
AB  - Two normal, two tumour, one transformed fibroblast cell line established from
      Ataxia telangiectasia (AT) patients and one corrected AT hybrid were
      characterised with regard to alpha, beta, SF2, and D values. Survival of 60Co
      gamma-irradiated tumour and transformed cells was markedly reduced when the Na+,
      K+-ATPase inhibitor ouabain was present 1 hr before and 3 hr post irradiation.
      Under these conditions, the radiosensitivity in normal cells remained virtually
      unchanged. Suppression of repair was found to play a role in the ouabain-induced
      inhibition of the cell survival. In A549 lung carcinoma cells, addition of 10(-8)
      M ouabain decreases the sublethal damage recovery ratio from 56.5 to 13.3. The
      same drug concentration decreases the recovery ratio in L132 epithelial cells
      only from 5.1 to 4.9. The fast repair component, as measured over the first 1.5
      hr after irradiation, decreases from 1.83 to 0.36 hr(-1) in A549 cells and from
      0.35 to 0.16 hr(-1) in HeLa cells. For 2 Gy fractions, the presence of 10(-8) M
      ouabain 1 hr before irradiation and 3 hr after irradiation induces dose
      enhancement ratios of 1.15-1.5. A more pronounced effect on cell inactivation may
      be expected from multiple fractions. The concentrations required to downregulate
      sublethal damage repair fall within the range where cardiac glycosides are used
      clinically. Application of these drugs in radiotherapy thus seems feasible.

PMID- 9652910
TI  - Measurement of proliferation activities in human tumor models: a comparison of
      flow cytometric methods.
AB  - Proliferating cells in tumors may be of considerable relevance in cancer therapy.
      Not only do such cells dictate the rate of tumor progression, but evidence exists
      that they may also play an important role in the diagnosis and prognosis of tumor
      regrowth. Consequently, the identification of this subset of cells in the overall
      neoplastic cell population is of considerable importance. The aim of the present
      investigations was to compare four flow cytometric methodologies commonly used to
      study cell proliferation. These included nuclear antigen Ki67 detection, acridine
      orange (AO) and bromodeoxyuridine (BrdUrd) staining, and percent S-phase
      determinations. Three human tumor cell lines (HEp3, A549, H226) were examined in
      various stages of growth. Further, a direct comparison was made of the
      proliferation activities of HEp3 cells grown in culture or as xenografts in nude
      mice. The results showed that of the techniques investigated, detection of the
      nuclear antigen Ki67 may be most useful for marking proliferating tumor cells and
      determining tumor growth fractions.

PMID- 9652911
TI  - Computed tomographic evaluation of radiation pneumonitis in a canine model.
AB  - The objective of this study was to document the utility of computed tomography
      (CT) and a three-dimensional (3-D) radiotherapy treatment planning system for
      assessing the development of acute radiation pneumonitis in a canine model.
      Fourteen dogs were randomly assigned to a nonirradiated control group or one of
      three radiation dose groups receiving a single fraction of either 12, 15, or 18
      Gy delivered to two-thirds of the right hemithorax. CT and survey radiographs
      were performed in all dogs prior to and at defined intervals for up to 13 weeks
      following irradiation. All images were subjectively evaluated for development of
      radiation pneumonitis and CT images were quantitatively analyzed. Radiation
      pneumonitis was detected earlier with CT images than with radiographs.
      Quantitatively, functional lung volume and radiation pneumonitis lesion volume on
      CT images changed over time in all irradiated dogs. However, there was no
      statistically significant difference between the three radiation dose groups, but
      a marked difference between irradiated dogs and nonirradiated controls. These
      data suggest that CT is superior to survey radiography for the evaluation and
      quantification of acute radiation pneumonitis in this canine model.
      Quantification of acute radiation pneumonitis suggests future promise for
      evaluating the efficacy of modifiers to lessen the effects of irradiating normal
      lung tissue in this canine model.

PMID- 9652912
TI  - Acute urinary morbidity following I-125 interstitial implantation of the prostate
      gland.
AB  - The objective of this paper was to evaluate the acute urinary morbidity
      associated with I-125 interstitial implantation of the prostate gland. From 1991
      1995, 117 patients underwent ultrasound (U/S)-guided implantation of the prostate
      gland. Median dose to 90% of the gland (d90) was 14.68 Gy (range = 1.65-21.75
      Gy). The patients' urinary symptoms were recorded pre-implantation and at regular
      intervals after implantation using the International Prostate Symptom Score
      (IPSS), a self-assessment questionnaire in which patients scored 7 symptoms:
      incomplete emptying, frequency, intermittency, urgency, weak stream, straining,
      and nocturia. Median follow-up was 12 months. The natural history of implant
      related urinary symptoms was assessed in this manner. In addition, dosimetric
      factors including U/S prostate volume, total activity, activity per seed, dose
      volume histogram (DVH) values for dose to gland, and dose area histogram (DAH)
      values for dose to urethra and bladder were examined for correlation to the
      severity of each symptom as well as to total IPSS (sum of the individual symptom
      scores). Total IPSS peaked at 1 month post-implant and gradually returned to
      approximately baseline at 24 months. Total IPSS directly correlated with total
      activity and DVH for the prostate. Total IPSS, however, did not correlate with
      bladder or urethral DAH. With the exception of frequency, individual symptoms did
      not correlate with dose to gland, bladder, or urethra. Frequency scores did,
      however, correlate not only with dose to prostate gland but also dose to urethra.
      The acute urinary side effects of I-125 prostate implantation are transient and
      peak at 1 month post-implant. The severity of the urinary irritative symptoms
      developed are closely related to total dose to the gland. Urethral dose appears
      to affect frequency most significantly. Urinary symptoms, therefore, may be a
      limiting factor when considering dose escalation with I-125.

PMID- 9652913
TI  - Clinical in vivo dosimetry using optical fibers.
AB  - Discoloring of glass due to ionizing radiation depends on the absorbed dose. The
      radiation-induced light attenuation in optical fibers may be used as a measure of
      the dose. In high-energy photon beams (6 MV X rays), a lead-doped silica fiber
      can be calibrated. A dosimeter based on an optical fiber was developed for
      applications in radiation therapy. The diameter of the mounted fiber is 0.25 mm,
      whereas the length depends on the sensitivity required. To demonstrate the
      applicability, a customized fiber device was used to determine scattered
      radiation close to the lens of the eye. Measurements were compared with TLDs
      (LiF) in an anthropomorphic phantom. The comparison with TLD measurements shows
      good agreement. In contrast to TLD, optical fibers provide immediate dose values,
      and the readout procedure is much easier. Owing to its small size and diameter,
      interesting invasive dose measurements are feasible.

PMID- 9652914
TI  - A.W. Liley Prize 1997 awarded to Prof. Erich Saling, MD, Berlin.

PMID- 9652916
TI  - Computer assisted learning.

PMID- 9652915
TI  - A single site on the epsilon subunit is responsible for the change in ACh
      receptor channel conductance during skeletal muscle development.

PMID- 9652917
TI  - Appointment of consultants.

PMID- 9652918
TI  - Good undergraduate teaching.

PMID- 9652919
TI  - Lyme disease vaccine given guarded approval in the US.

PMID- 9652920
TI  - Retraction. Evidence of unmet need in the care of physically disabled adults.

PMID- 9652921
TI  - Dealing with research misconduct in the United Kingdom. Conduct unbecoming--the
      MRC's approach.

PMID- 9652922
TI  - Dealing with research misconduct in the United Kingdom. An editor's response to
      fraudsters.

PMID- 9652923
TI  - Dealing with research misconduct in the United Kingdom. Deception: difficulties
      and initiatives.

PMID- 9652924
TI  - Dealing with research misconduct in the United Kingdom. Honest advice from
      Denmark.

PMID- 9652925
TI  - What should a junior doctor have done?

PMID- 9652926
TI  - You cannot expect people to be heroes.

PMID- 9652927
TI  - Put out the fire or risk an inferno.

PMID- 9652928
TI  - Present system of whistleblowing is unsatisfactory.

PMID- 9652929
TI  - Research assessment exercise. Some of author's suggestions were misleading.

PMID- 9652930
TI  - Research assessment exercise. Departments do not know rules of exercise.

PMID- 9652931
TI  - Research assessment exercise. Exercise has implications for clinical academic
      medicine.

PMID- 9652932
TI  - Measles, measles vaccination, and Crohn's disease. Crohn's disease has not
      increased in Finland.

PMID- 9652933
TI  - Measles, measles vaccination, and Crohn's disease. Age specific prevalences do
      not suggest association with in utero exposure.

PMID- 9652934
TI  - Milk intake and bone mineral acquisition in adolescent girls. Adding milk to
      adolescent diet may not be best means of preventing osteoporosis.

PMID- 9652935
TI  - Milk intake and bone mineral acquisition in adolescent girls. Results in two
      groups are not so different.

PMID- 9652936
TI  - Resuscitation. Some aspects of 1997 guidelines are less helpful than old
      guidelines.

PMID- 9652937
TI  - Resurgence of interest in medical oaths and codes of conduct. Killing can never
      be morally acceptable.

PMID- 9652938
TI  - The "Diana effect". Number of inappropriate hospital admissions increased.

PMID- 9652939
TI  - The "Diana effect". There was no "Diana effect" on numbers of psychiatric
      emergencies.

PMID- 9652940
TI  - Approval given for trials of AIDS vaccine.

PMID- 9652941
TI  - MMR vaccination and autism 1998. Medical practitioners need to give more than
      reassurance.

PMID- 9652942
TI  - MMR vaccination and autism 1998. Those giving MMR vaccine had no input into
      editorial.

PMID- 9652943
TI  - The health of Gypsies. Governments and Roma communities must help to improve
      outlook for Gypsies.

PMID- 9652944
TI  - Exceptionalism in HIV. Past experience has been ignored.

PMID- 9652945
TI  - Audit commission tackles anaesthetic services. Non-physician anaesthetists may
      free up consultants to concentrate on patients requiring special attention.

PMID- 9652946
TI  - Audit commission tackles anaesthetic services. Quoted paper did not say that
      participation of nurses makes adverse outcomes more common.

PMID- 9652947
TI  - Audit commission tackles anaesthetic services. Investment is required to increase
      number of consultant anaesthetists.

PMID- 9652948
TI  - Urgency and priority models. Distinction between urgency and priority helps no
      one.

PMID- 9652949
TI  - Providing letters to patients. GPs can be given copies of letters sent to
      patients.

PMID- 9652950
TI  - Providing letters to patients. Letters should be used carefully.

PMID- 9652951
TI  - Providing letters to patients. Summary letters may be especially appropriate
      after emergency admissions.

PMID- 9652952
TI  - [Conference on problems of apoptosis. Moscow, 14-16 October 1996].

PMID- 9652953
TI  - Kinetic and thermodynamic principles determining the structural design of ATP
      producing systems.
AB  - It is theoretically analysed whether the structural design of ATP-producing
      pathways, in particular the design of glycolysis, may be explained by
      optimization principles. On the basis of kinetic and thermodynamic principles
      conclusions are derived concerning the stoichiometry of these pathways in states
      of high ATP production rates. One of the extensions to previous investigations is
      that the concentrations of the adenine nucleotides are taken into account as
      variable quantities. This necessitates the consideration of an interaction of the
      ATP-producing system I with an external ATP-consuming system II. A great variety
      of pathways is studied which differ in the number and location of ATP-consuming
      reactions, ATP-producing reactions and reactions involving inorganic phosphate.
      The corresponding number of possible pathways may be calculated in an explicit
      manner as a function of the number of those reactions which do not couple to ATP
      or inorganic phosphate. The kinetics of the individual reactions are described by
      linear or bilinear functions of reactant concentrations and all rate equations
      are expressed in terms of equilibrium constants and characteristic times. A
      thermo-dynamical analysis of the two coupled systems yields upper and lower
      limits for the concentration of ATP and an explicit expression for the maximal
      difference between the number of ATP-producing and ATP-consuming reactions of
      system I. The following results of the optimization are obtained. (i) The ATP
      production rate always increases if the ATP-producing reactions as well as those
      reactions characterized by an uptake of inorganic phosphate are shifted as far as
      possible towards the end of system I. (ii) Explicit conditions for the optimal
      location of the ATP-consuming reactions are presented. The results are discussed
      in the context of characteristic times as well as in terms of enzyme kinetic
      parameters. (iii) For two sets of characteristic times the resulting
      stoichiometries and their corresponding steady-state fluxes are investigated in
      detail. One of these stoichiometries shows a close correspondence to contemporary
      standard glycolysis. (iv) It is shown that most possible pathways result in a
      very low steady-state flux, that is, the optimal stoichiometry is characterized
      by a significant selective advantage. (v) The standard free energy profile of a
      pathway with an optimal stoichiometry is discussed. It differs significantly from
      the free energy profiles of nonoptimized pathways.

PMID- 9652954
TI  - International League against Epilepsy (British Branch) annual scientific meeting.
      Oxford, October 1997. Abstracts.

PMID- 9652955
TI  - [On the 80th birthday of Oleksandr Oleksiiovych Shalimov].

PMID- 9652956
TI  - [Biochemistry of presenilin 1].
AB  - The majority of cases of early-onset familial Alzheimer disease are caused by
      mutations in the recently identified presenilin 1 (PS 1) gene, located on
      chromosome 14. PS1, a 467 amino acid protein, is predicted to be an integral
      membrane protein containing seven putative transmembrane domains and a large
      hydrophilic loop between the sixth and seventh membrane-spanning domain. We
      produced 7 monoclonal antibodies that react with 3 non-overlapping epitopes on
      the N-terminal hydrophilic tail of PS1. The monoclonal antibodies can detect the
      full size PS1 at M(r) 47,000 (47K) and a more abundant M(r) 28,000 (28K) product
      in membrane from human brain and human cell lines. We examined the sub-cellular
      localization by using these antibodies. Immuno-electronmicroscopic and
      biochemical analysis indicated that PS1 is localized on cellular membrane
      (plasma, endoplasmic reticulum, and perinuclear) in COS-7 cells overexpressing
      PS1. Interestingly, the PS1 immunoreactivity in the plasma membrane was
      concentrated in the regions with cell-cell contact. This observation suggests a
      possible role of PS1 on the cell membrane as a cell adhesion molecule. To
      determine the protease cleaving the full length PS1 to two fragments, we treated
      cells with various protease inhibitors. Only proteasome inhibitor affected the
      PS1 processing, indicating that proteasome is a candidate protease for PS1
      proteolytic cleavage. PC12 cells transiently transfected with PS1 constructs
      containing different Alzheimer mutations fail to generate the 28K degradation
      product in contrast to PC12 cells transfected with wild type PS1. Our results
      indicate that missense mutations in this form of familial Alzheimer disease may
      act via a mechanism of impaired proteolytic processing of PS1.

PMID- 9652957
TI  - Leadership in child advocacy.

PMID- 9652958
TI  - Implant ID cards.

PMID- 9652959
TI  - An infection control procedure that is the patient's responsibility.

PMID- 9652960
TI  - Society of Oral Physiology, Store Kro Group, 20th biennial meeting. Lattrop, the
      Netherlands, 22-25 May 1997. Abstracts.

PMID- 9652961
TI  - Acetaminophen: a clarification.

PMID- 9652962
TI  - Which Ca2+ channels control cardiac E-C coupling?

PMID- 9652963
TI  - [Molecular Biology 30th Anniversary Conference. Moscow, December 17-19, 1997.
      Abstracts].

PMID- 9652964
TI  - More on school health and the pediatrician.

PMID- 9652965
TI  - More on the role of the school in ADHD.

PMID- 9652966
TI  - More on the role of the school in ADHD.

PMID- 9652967
TI  - Personal digital assistants. Another step toward ubiquitous computing.

PMID- 9652968
TI  - Effects of smoking on the periodontium.

PMID- 9652969
TI  - Evidence that elevated plasma corticosterone levels are the cause of reduced
      hypothalamic corticotrophin-releasing hormone gene expression in diabetes.
AB  - Uncontrolled diabetes mellitus causes both a sustained activation of the
      hypothalamic-pituitary-adrenal (HPA) axis and reduced expression of
      corticotrophin-releasing hormone (CRH) mRNA in the hypothalamic paraventricular
      nucleus (PVN). To investigate the role of glucocorticoids in the regulation of
      CRH mRNA expression in the PVN of diabetic rats, we studied surgically
      adrenalectomized (ADX) and sham-operated male Sprague-Dawley rats 4 days after
      i.v. injection of streptozotocin (STZ; 65 mg/kg i.v.) or vehicle. Among sham
      operated animals, AM plasma corticosterone levels were significantly increased in
      diabetic as compared to nondiabetic animals (1.46+/-0.54 vs. 0.22+/-0.05
      microg/dl; P <0.05), and were positively correlated to both plasma ACTH levels (r
      = 0.74; P = 0.015) and adrenal gland weight (r = 0.70; P = 0.025). In contrast,
      CRH mRNA levels measured in the PVN by in situ hybridization were inversely
      related to the plasma corticosterone level (r = -0.68; P = 0.045). In a second
      experiment, both diabetic and nondiabetic ADX rats received a continuous
      subcutaneous infusion of either corticosterone at one of two doses or its vehicle
      for 4 days. Among vehicle-treated ADX animals, STZ diabetes raised hypothalamic
      CRH mRNA levels, in contrast to the tendency for diabetes to lower CRH mRNA in
      intact rats in the first experiment. Corticosterone administration lowered CRH
      mRNA comparably in both diabetic and nondiabetic ADX rats. In contrast, diabetes
      reduced arginine vasopressin (AVP) mRNA levels in the PVN of ADX rats and blunted
      the inhibitory effect of glucocorticoids on AVP mRNA levels in this setting. We
      conclude (1) glucocorticoids are necessary for the effect of diabetes to reduce
      hypothalamic CRH gene expression, since diabetes causes a paradoxical increase in
      CRH mRNA levels in adrenalectomized animals; (2) glucocorticoid inhibition of
      hypothalamic CRH gene expression is intact in diabetic rats; and (3) the
      activation of the HPA axis by diabetes is associated with a proportionate
      decrease in PVN CRH gene expression. These findings support a model in which
      hypothalamic factors additional to CRH activate the HPA axis in uncontrolled
      diabetes, and inhibit CRH gene expression indirectly by negative glucocorticoid
      feedback.

PMID- 9652970
TI  - Pharmacological characterization and selectivity of the NPY antagonist GR231118
      (1229U91) for different NPY receptors.
AB  - Neuropeptide Y (NPY) is widely distributed throughout the central and peripheral
      nervous system and exerts a wide range of physiological responses by activating
      specific receptors. In this study we have characterized the potency of the high
      affinity peptide dimer antagonist, GR231118, to displace radiolabeled NPY/PYY
      from different tissues and cell lines expressing Y1 or Y2 receptors and from CHO
      cells stably transfected with human cDNA encoding for Y1, Y2 and Y4 receptors.
      GR231118 displays high affinity for Y1 and Y4 receptors, equal or better than
      that of NPY itself, while its activity is several fold weaker for Y2 receptors.
      Displacement of radiolabeled PYY from rat hypothalamic membranes by GR231118,
      reveals the existence of high and low affinity binding sites which may be equated
      to Y1 and Y2 receptors respectively suggesting that the compound maybe used as a
      tool to dissect central NPY receptors.

PMID- 9652971
TI  - Increased receptor sensitivity to neuropeptide Y in the hypothalamus may underlie
      transient hyperphagia and body weight gain.
AB  - Disruption of neural signaling by microinjection of a neurotoxin, colchicine
      (COL), in the ventromedial hypothalamus (VMH) of rats results in rapid and
      transient hyperphagia and body weight gain. Since neuropeptide Y (NPY) is a
      potent hypothalamic orexigenic signal and continuous NPY receptor activation by
      intracerebroventricular (icv) NPY infusion results in hyperphagia and obesity, we
      tested the hypothesis that altered NPYergic signaling may underlie the transient
      hyperphagia in COL-injected rats. Immediately following COL (4 microg)
      microinjections in the ventromedial nucleus (VMN) rats displayed hyperphagia both
      during the lights-on and lights-off periods. Concomitant with hyperphagia,
      preproNPY mRNA levels in the arcuate nucleus and NPY levels in the
      paraventricular nucleus decreased in a time-dependent manner. However, food
      intake in response to intracerebroventricular injections of NPY (29, 117 and 470
      pmole) was significantly higher in COL-injected rats and the latency to
      initiation of feeding was markedly reduced as compared to controls. The smallest
      dose of NPY which was virtually ineffective in control rats, evoked near maximal
      intake in COL-injected rats. This enhanced response lasted for only 4 days
      paralleling the transient hyperphagia. The NPY Y1 receptor antagonist 1229U91 (5
      or 30 microg/rat, icv) significantly suppressed feeding in COL-treated rats
      thereby indicating that hyperphagia in these rats was dependent upon endogenous
      NPY. Overall, these studies demonstrate that not only high levels, but low levels
      of NPY may also result in hyperphagia and increased body weight and this
      hyperphagia may be attributed to the rapid development of NPY Y1 receptor
      hypersensitivity.

PMID- 9652972
TI  - Endogenous CCK inhibits colonic contractions in unrestrained conscious rats.
AB  - As cholecystokinin octapeptide (CCK-OP) and feeding have been reported to relax
      the circular muscle contractions of the proximal colon in unrestrained conscious
      rats under fasting conditions, the, action of cholecystokinin, released after
      duodenal infusion of a low residual diet of clinimeal, was studied on the motor
      activity of the proximal colon in unrestrained conscious rats. We used an
      implantable telemetry system with a miniature strain gauge force transducer
      introduced into the rat proximal colon. By using a specific radioimmunoassay
      system for CCK, plasma levels of CCK before and after duodenal infusion of
      clinimeal (0.5, 1.0, 2.0 ml) were determined at 0, 5, 10, 20, 30, 60 min in the
      portal blood. The clinimeal infusion caused a significant increase in CCK levels
      of the portal plasma during 5 and 30 min. This increase was in a dose-dependent
      manner. In accordance with this increase in plasma CCK, the motor activity of the
      proximal circular muscle was suppressed significantly. A bolus injection of the
      CCK A receptor antagonist, loxiglumide, CR 1505 (0.1, 0.5 and 1.0 mg/kg ip),
      prior to clinimeal blocked the inhibitory action of CCK on the motor activity in
      a concentration-dependent manner. These data suggest that endogenous CCK released
      by a residual diet is involved in the mechanism of inhibition of motor activity
      in the proximal colon.

PMID- 9652973
TI  - Angiotensin receptors and norepinephrine neuromodulation: implications of
      functional coupling.
AB  - The objective of this review is to examine the role of neuronal angiotensin II
      (Ang II) receptors in vitro. Two types of G protein-coupled Ang II receptors have
      been identified in cardiovascularly relevant areas of the brain: the AT1 and the
      AT2. We have utilized neurons in culture to study the signaling mechanisms of AT1
      and AT2 receptors. Neuronal AT1 receptors are involved in norepinephrine (NE)
      neuromodulation. NE neuromodulation can be either evoked or enhanced. Evoked NE
      neuromodulation involves AT1 receptor-mediated, losartan-dependent, rapid NE
      release, inhibition of K+ channels and stimulation of Ca2+ channels. AT1 receptor
      mediated enhanced NE neuromodulation involves the Ras-Raf-MAP kinase cascade and
      ultimately leads to an increase in NE transporter, tyrosine hydroxylase and
      dopamine beta-hydroxylase mRNA transcription. Neuronal AT2 receptors signal via a
      Gi protein and are coupled to activation of PP2A and PLA2 and stimulation of K+
      channels. Finally, putative cross-talk pathways between AT1 and AT2 receptors
      will be discussed.

PMID- 9652974
TI  - PACAP stimulates pancreatic exocrine secretion via the vagal cholinergic nerves
      in sheep.
AB  - The present study evaluates the possible role of the vagus nerves in mediating
      the stimulatory effect of PACAP-27, PACAP-38 and VIP on the exocrine pancreas,
      especially on enzyme secretion which is atropine sensitive in sheep. The animals
      were equipped with two cannulae into the common bile duct, a duodenal cannula,
      and a ruminal cannula under anesthesia. The bilateral cervical vagus nerves were
      coiled with a cooling device. In conscious animals, the peptides were infused
      intravenously for 10 min at 10 pmol kg(-1)min(-1) in phase II of the duodenal
      migrating motor complexes and the same peptide infusion was repeated in the
      reversible cooling blockade of the vagus nerves. Increment in fluid secretion was
      not significantly altered by the vagal blockade in all the peptide infusions,
      while increment in bicarbonate ion by only PACAP-27 was inhibited by the vagal
      blockade. Increments in protein and amylase output decreased significantly to
      32.0+/-5.0 and 23.2+/-2.6% in PACAP27, and to 26.1+/-7.7 and 20.8+/-6.4% in PACAP
      38 in the vagal blockade, but the increments by VIP did not decrease. These
      results demonstrate that circulating PACAP stimulates pancreatic enzyme secretion
      via the vagal cholinergic preganglionic neurons in sheep, suggesting the central
      action of PACAP.

PMID- 9652975
TI  - Renal aminopeptidase activities in animal models of hypertension.
AB  - Aminopeptidase activity (AP) has been implicated in the metabolism of renal and
      circulating vasoactive peptides. This activity is involved in the pathogenia of
      hypertension, essentially in spontaneously hypertensive rats. However, no other
      animal models, which develop hypertension by other different ways, have been used
      to study the possible role of aminopeptidase activity. To investigate the role of
      this activity in the pathogenesis of hypertension, angiotensinase A activity
      (glutamyl-AP and aspartyl-AP), aminopeptidase M activity (alanyl-AP),
      aminopeptidase B activity (arginyl-AP), pyroglutamyl-AP, and cystinyl-AP were
      measured in the serum and kidney of two experimental animal models of
      renovascular hypertension: Goldblatt two-kidney one clip (G2K-1C) and low renal
      mass rats (LRM). No differences were found in serum levels of AP in LRM or G2K-1C
      in comparison with their respective controls. In LRM rats there was a significant
      decrease in membrane-bound angiotensinase A (glutamyl-AP), arginyl-AP and alanyl
      AP activities. In G2K-1C rats there was a significant decrease in soluble and
      membrane-bound angiotensinase A activity (aspartyl-AP). Our results suggest that
      AP activities play a role in the regulation of renal vasoactive peptides, and
      respond differently depending on the cause of hypertension.

PMID- 9652976
TI  - Prolonged pheromonotropic activity of pseudopeptide mimics of insect pyrokinin
      neuropeptides after topical application or injection into a moth.
AB  - Amphiphilic pseudopeptide analogs of Phe-Thr-Pro-Arg-Leu-NH2, representing the
      active C-terminal core pentapeptide of the pyrokinin class of insect
      neuropeptides, were synthesized by replacement of phenylalanine with
      hydrocinnamic acid (Hca-Thr-Pro-Arg-Leu-NH2), or addition of 1-pyrenebutyric acid
      (Pba-Phe-Thr-Pro-Arg-Leu-NH2) or 9-fluoreneacetic acid (Fla-Phe-Thr-Pro-Arg-Leu
      NH2). The pseudopeptides were found to stimulate sex pheromone biosynthesis when
      injected into females of the moth Heliothis virescens. Optimal pheromonotropic
      responses were obtained by injection of 0.25 pmol of Hca-Thr-Pro-Arg-Leu-NH2, 2.5
      pmol of Pba-Thr-Pro-Arg-Leu-NH2 and 0.5 pmol of Fla-Thr-Pro-Arg-Leu-NH2. Topical
      application of each of the pseudopeptides in water to the cuticle of moths
      stimulated significant production of pheromone at a dose of 50 pmol with optimal
      stimulation occurring when 500 pmol were applied. The parent peptide, Phe-Thr-Pro
      Arg-Leu-NH2, failed to stimulate significant production of pheromone when applied
      topically at a dose as high as 2000 pmol. Temporal studies indicated that Hca-Thr
      Pro-Arg-Leu-NH2 stimulated significant production of pheromone for only 4 h after
      application where as continuous pheromone production for 18 h was observed when
      either Pba-Phe-Thr-Pro-Arg-Leu-NH2 or Fla-Phe-Thr-Pro-Arg-Leu-NH2 were applied to
      the abdomen. The results show that modification of the C-terminal active core of
      the insect pyrokinins, by addition of hydrophobic moieties, can result in
      production of pseudopeptides which effectively penetrate the insect cuticle and
      have prolonged physiological effects making them favorable candidates for use in
      development of alternative strategies for pest insect control.

PMID- 9652977
TI  - Neutrophil extracted lipocortin inhibits corticotropin secretion in the AtT-20
      D16:16 clonal mouse pituitary cell line. Lipocortin inhibition of ACTH release in
      vitro.
AB  - The mechanism of short-term glucocorticoid (GC) inhibition of the hypothalamic
      pituitary-adrenal axis is not well understood. The direct anti-inflammatory
      activities of lipocortins (LCs) have suggested a role for them as extra- and
      intracellular mediators of the biological effects of GCs. It has been reported
      that recombinant human (rh) LC1 inhibits corticotropin (ACTH) release from
      pituitary tissue in vitro but not from AtT-20 D16:16 corticotrophs. Using the
      same cell line we have tested whether other exogenous rhLCs or native LC
      extracted from polymorphonucleate neutrophils (neLC), likely LC1, have an effect
      on ACTH secretion. It is shown that: (1) basal release was not affected by a
      short-term incubation with neLC; (2) secretion induced by corticotropin-releasing
      factor (CRF) and other secretagogues (phorbol ester, potassium ion or calcium
      ionophore) was inhibited by neLC; (3) GC inhibition of CRF-stimulated release was
      reverted by a monoclonal anti-neLC antibody; (4) rhLC2, rhLC5 and the fragment
      212-234 of rhLC5 were without effect. Thus, only neLC is effective on AtT-20
      D16:16 cells, suggesting for this annexin a role in the early phase GC inhibition
      of ACTH secretion.

PMID- 9652978
TI  - Urinary excretion of epidermal growth factor and Tamm-Horsfall protein in three
      rat models with increased renal excretion of urine.
AB  - Epidermal growth factor (EGF) and Tamm-Horsfall protein (THP) are synthesized in
      the kidneys by the distal tubular cells and excreted into urine. The urinary
      excretion of these peptides has been suggested as a potential index for distal
      tubular function. The urinary excretion rates of EGF and THP were examined in
      three groups of rats with increased renal excretion of urine: uninephrectomy, non
      osmotic polyuria and diabetic osmotic polyuria. Twenty-four hour urine samples
      were obtained after 7, 14 and 21 days. The urinary volume per kidney was doubled
      in uninephrectomy when compared to controls. There was a seven-fold increase in
      urinary volume in rats with non-osmotic polyuria and diabetic osmotic polyuria,
      as compared to controls. Uninephrectomy, non-osmotic polyuria and diabetes all
      affected the urinary excretion of EGF and THP differently. The EGF excretion in
      uninephrectomized rats was 60-80% of that of the controls, whereas THP excretion
      was unchanged, indicating that EGF excretion varied with renal tissue mass. Non
      osmotic polyuria caused a five-fold increase in THP excretion but no change in
      EGF excretion. THP excretion in the diabetic rats was increased three-fold after
      21 days when compared to controls, whereas EGF excretion was decreased when
      expressed per kidney weight. Immunohistochemistry demonstrated that EGF and THP
      were colocalized in the thick ascending limbs of Henle's loops and distal tubules
      in all five groups of rats. In conclusion, the EGF excretion appears to follow
      renal tissue mass and seems independent of urinary volume, whereas THP excretion
      is dependent mainly on urinary volume. This has implications for the use of EGF
      and/or THP excretion rates as an indicator for distal tubular function.

PMID- 9652979
TI  - Functional impairment of the individual rat stomach ECL cell in response to
      sustained hypergastrinemia.
AB  - ECL cells in the oxyntic mucosa secrete histamine and pancreastatin in response
      to gastrin. The present study examined gastrin-evoked ECL-cell responses over a
      10-week time span in terms of individual ECL cells and unit ECL cell volume. Rats
      were treated with omeprazole (400 micromol/kg per day orally). The concentrations
      of gastrin and pancreastatin in serum and of histamine and pancreastatin in the
      oxyntic mucosa were measured as was the activity of the oxyntic mucosal histidine
      decarboxylase (HDC). The ECL cells were visualized by immunostaining of histamine
      and examined by electron microscopy. The total ECL cell number and volume, and
      the mean ECL cell diameter and volume were determined. The HDC, chromogranin A
      (CGA) and cholecystokinin-B (CCK-B) receptor mRNA concentrations were determined.
      In terms of individual ECL cells and unit ECL cell volume, the serum
      pancreastatin concentration, the oxyntic mucosal histamine content, HDC activity,
      and HDC, CGA and CCK-B receptor mRNA contents increased slowly at first and then
      leveled off or started to decline after 2 weeks. After 10 weeks all ECL-cell
      parameters (expressed per unit ECL cell volume) were back to or approaching the
      starting value. In conclusion, sustained hypergastrinemia first activates each
      individual ECL cell (with a peak after 1-2 weeks) and then causes gradual
      functional impairment, the activity returning towards the pre-stimulation level.

PMID- 9652980
TI  - CGRP and substance P in intraepithelial neuronal structures of the human upper
      respiratory system.
AB  - The distribution of intraepithelial nerve fibres and neuroendocrine cells within
      the surface and glandular epithelium of human nasal mucosa and larynx was
      examined using immunohistochemical techniques. Neuronal structures were
      immunostained for the general neuroendocrine marker protein gene-product (PGP)
      9.5, and the two neuropeptides substance P (SP) and calcitonin gene-related
      peptide (CGRP) using immunofluorescence and streptavidin-biotin-peroxidase
      complex (S-ABC) methods. Intraepithelial nerve fibres with free nerve endings
      contained PGP 9.5 and were found within the respiratory surface epithelium of the
      nasal mucosa and the squamous epithelium of the larynx. A subpopulation of these
      nerve fibres showed positive immunoreactivties with antibodies against SP and
      CGRP. Nerve fibres within the ductal epithelium of subepithelial excretory ducts
      passing the basal membrane and reaching the luminal part were detected. These
      nerve fibres showed CGRP-like immunoreactivity but not for SP. A dense network of
      nerve fibres within the squamous surface epithelium was detected in the
      subglottic and epiglottic region containing CGRP and SP in a small subpopulation
      of nerve fibres. Single intraepithelial taste buds in the epiglottic region and
      neuroendocrine cells within the subglottic epithelium expressed PGP 9.5.

PMID- 9652981
TI  - Effects of OPC-21268, a vasopressin V1-receptor antagonist, on expression of
      growth factors from glomeruli in spontaneously hypertensive rats.
AB  - To assess the chronic in vivo effects of OPC-21268, a vasopressin-V1 receptor
      antagonist, on renal injury, we investigated the mRNA expressions of platelet
      derived growth factor (PDGF) B-chain, transforming growth factor (TGF)-beta1 and
      proliferating cell nuclear antigen (PCNA) in the glomeruli of spontaneously
      hypertensive rats (SHR) treated with OPC-21268 for 3 weeks. SHR aged 10 weeks
      were given 2% NaCl in drinking water for 3 weeks. The OPC group was fed a 0.5%
      OPC-21268-containing diet for 3 weeks and the control group was given a normal
      diet. There were no significant changes in the time course of systolic blood
      pressure, heart rate, urine volume, or urinary sodium, protein and N-acetyl-beta
      glucosaminidase (NAG) excretion between the two groups. Serum electrolytes,
      protein and creatinine levels also did not differ between the groups. The mRNA
      expressions of PDGF B-chain, TGF-beta1 and PCNA in the glomerulus were examined
      using reverse transcriptase-polymerase chain reaction (RT-PCR) methods. The mRNA
      expressions of PDGF B-chain and PCNA among these were significantly suppressed in
      the OPC group. No significant differences in renal histology including the organ
      weights were found between the two groups; however, the glomerular size tended to
      be enlarged in the OPC group. These findings suggest that chronic V1-receptor
      blockade directly inhibits the glomerular proliferative injury of salt-loaded SHR
      at the established hypertension stage.

PMID- 9652982
TI  - Mutational analysis of the angiotensin II type 2 receptor: contribution of
      conserved extracellular amino acids.
AB  - While much work has been done examining the ligand-binding characteristics of the
      AT1 receptor, very little attention has been focused on the AT2 receptor. Both
      receptors bind angiotensin II (AngII) with identical affinities, but share only
      34% homology. Although it is tempting to assume that conserved residues between
      the two subtypes are responsible for the binding of AngII, there is little data
      to support this view. To determine the commonalities in ligand binding of the AT1
      and AT2 receptors, we have chosen several conserved extracellular amino acids
      which have been shown to be important in AngII binding [1,2] to the AT1 receptor
      for mutational studies of the AT2 receptor. Specifically, we have mutated
      tyrosine108 in extracellular loop 1 (ECL1), arginine182 in ECL2, and aspartate297
      in ECL3 of the AT2 receptor in order to determine their contribution to AngII
      binding. In the AT2 receptor, mutation of tyrosine108 to an alanine resulted in a
      receptor with wild-type binding for AngII, while mutation of either arginine182
      or aspartate297 drastically impaired AngII binding ( > 100 nM). These results
      demonstrate both similarities as well as clear differences between receptor
      subtypes in the contributions to AngII binding of several conserved extracellular
      amino acid residues.

PMID- 9652983
TI  - Proceedings of the 8th International Symposium of Nephrology. Montecatini Terme,
      Italy, October 7-9, 1996.

PMID- 9652984
TI  - Frequency of HIV testing and diagnosis in a KwaZulu-Natal regional hospital.

PMID- 9652985
TI  - Proceedings, white pages, and recommendations from the consensus conference on
      developing practice guidelines for institutionalized older dental patients.

PMID- 9652986
TI  - [A new generation of anti-allergic preparations: an expansion of the therapeutic
      possibilities].

PMID- 9652987
TI  - [Transurethral endoscopic electrovaporization in the treatment of patients with
      benign prostatic hyperplasia].

PMID- 9652988
TI  - [Georgii Semenovich Grebenshchikov (on the centenary of his birth)].

PMID- 9652989
TI  - [Schoenlein-Henoch purpura with intestinal involvement].

PMID- 9652990
TI  - [Transmission of hepatitis C in gastrointestinal endoscopy--media sensationalism
      or a clinically relevant problem?].

PMID- 9652991
TI  - Miss-'n-mix and mimics. Emergency drugs.

PMID- 9652992
TI  - Report of the NIH Panel To Define Principles of Therapy of HIV Infection.
AB  - Recent research advances have afforded substantially improved understanding of
      the biology of HIV infection and the pathogenesis of AIDS. With the advent of
      sensitive tools for monitoring HIV replication in infected persons, the risk for
      disease progression and death can be assessed accurately and the efficacy of anti
      HIV therapies can be determined directly. Furthermore, when used appropriately,
      combinations of newly available, potent antiviral therapies can effect prolonged
      suppression of detectable levels of HIV replication and circumvent the inherent
      tendency of HIV to generate drug-resistant viral variants. However, as
      antiretroviral therapy for HIV infection has become increasingly effective, it
      has also become increasingly complex. Familiarity with recent research advances
      is needed to ensure that newly available therapies are used in ways that most
      effectively improve the health and prolong the lives of HIV-infected persons. To
      enable practitioners and HIV-infected persons to best use rapidly accumulating
      new information about HIV disease pathogenesis and treatment, the Office of AIDS
      Research of the National Institutes of Health (NIH) sponsored the NIH Panel To
      Define Principles of Therapy of HIV Infection. This Panel was asked to define
      essential scientific principles that should be used to guide the most effective
      use of antiretroviral therapies and viral load testing in clinical practice. On
      the basis of detailed consideration of the most current data, the Panel
      delineated 11 principles that address issues of fundamental importance for the
      treatment of HIV infection. These principles provide the scientific basis for the
      specific treatment recommendations made by the Panel on Clinical Practices for
      the Treatment of HIV Infection sponsored by the Department of Health and Human
      Services and the Henry J. Kaiser Family Foundation. The reports of both of these
      panels are provided in this supplement. Together, they summarize new data and
      provide both the scientific basis and specific guidelines for the treatment of
      HIV-infected persons. This information will be of interest to health care
      providers, HIV-infected persons, HIV and AIDS educators, public health educators,
      public health authorities, and all organizations that fund medical care of HIV
      infected persons.

PMID- 9652993
TI  - Guidelines for the use of antiretroviral agents in HIV-infected adults and
      adolescents. Department of Health and Human Services and the Henry J. Kaiser
      Family Foundation.

PMID- 9652994
TI  - The effect of sodium monofluorophosphate plus calcium on vertebral fracture rate
      in postmenopausal women with moderate osteoporosis. A randomized, controlled
      trial.
AB  - BACKGROUND: Fluoride is effective in increasing trabecular bone mineral density
      (BMD) in the spine, but its efficacy in reducing vertebral fracture rates and its
      effect on BMD at cortical sites are controversial. OBJECTIVE: To study the effect
      of low-dose fluoride (sodium monofluorophosphate [MFP]) plus a calcium supplement
      over 4 years on vertebral fractures and BMD at the lumbar spine and total hip in
      postmenopausal women with moderately low BMD of the spine. DESIGN: Randomized,
      double-blind, controlled clinical trial. SETTING: Outpatient clinic for
      osteoporosis at a university medical center. PATIENTS: 200 postmenopausal women
      with osteoporosis (according to the World Health Organization definition) and a T
      score less than -2.5 for BMD of the spine. INTERVENTION: Women were randomly
      assigned (100 patients per group) to continuous daily treatment for 4 years with
      1) oral MFP (20 mg of equivalent fluoride) plus 1000 mg of calcium (as calcium
      carbonate) or 2) calcium only. MEASUREMENTS: Lateral spine radiographs were taken
      at enrollment and at each year of follow-up for detection of new vertebral
      fractures (defined as a reduction > or =20% and > or =4 mm from baseline in any
      of the heights of a vertebral body). Nonvertebral fractures were also recorded.
      All analyses were done with the intention-to-treat approach. RESULTS: Radiologic
      follow-up was possible for 164 of 200 patients (82%). The rate of new vertebral
      fractures during the 4 years of the study was lower in the MFP-plus-calcium group
      (2 of 84 patients; 2.4% [95% CI, 0.3% to 8.3%]) than in the calcium-only group (8
      of 80 patients; 10% [CI, 4.4% to 18.8%]). The difference between the groups was
      7.6 percentage points (CI, 0.3 to 15 percentage points) (P = 0.05). A moderate
      but progressive increase in BMD of the spine (10.0% +/- 1.5% at 4 years) was
      found for MFP plus calcium compared with calcium only (P < 0.001), whereas the
      more modest increase in BMD of the total hip seen with MFP plus calcium (1.8% +/-
      0.6%) did not differ from the increase seen with calcium only. CONCLUSIONS: Low
      dose fluoride (20 mg/d) given continuously with calcium for prolonged periods can
      decrease vertebral fracture rates compared with calcium alone in patients with
      mild to moderate osteoporosis.

PMID- 9652995
TI  - Effects of androgen administration in men with the AIDS wasting syndrome. A
      randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Development of successful anabolic strategies to reverse the loss of
      lean body mass is of critical importance to increase survival in men with the
      AIDS wasting syndrome. Hypogonadism, an acquired endocrine deficiency state
      characterized by loss of testosterone, occurs in more than half of all men with
      advanced HIV disease. It is unknown whether testosterone deficiency contributes
      to the profound catabolic state and loss of lean body mass associated with the
      AIDS wasting syndrome. OBJECTIVE: To investigate the effects of physiologic
      testosterone administration on body composition, exercise functional capacity,
      and quality of life in androgen-deficient men with the AIDS wasting syndrome.
      DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: University
      medical center. PATIENTS: 51 HIV-positive men (age 42 +/- 8 years) with wasting
      (body weight < 90% of ideal body weight or weight loss > 10% of baseline weight)
      and a free testosterone level less than 42 pmol/L (normal range for men 18 to 49
      years of age, 42 to 121 pmol/L [12.0 to 35.0 pg/mL]). INTERVENTION: Patients were
      randomly assigned to receive testosterone enanthate, 300 mg, or placebo
      intramuscularly every 3 weeks for 6 months. MEASUREMENTS: Change in fat-free mass
      was the primary end point. Secondary clinical end points were weight, lean body
      mass, muscle mass, exercise functional capacity, and change in perceived quality
      of life. Virologic variables were assessed by CD4 count and viral load. RESULTS:
      Compared with patients who received placebo, testosterone-treated patients gained
      fat-free mass (-0.6 kg and 2.0 kg; P = 0.036), lean body mass (0.0 kg and 1.9 kg;
      P = 0.041), and muscle mass (-0.8 kg and 2.4 kg; P = 0.005). The changes in
      weight, fat mass, total-body water content, and exercise functional capacity did
      not significantly differ between the groups. Patients who received testosterone
      reported benefit from the treatment (P = 0.036), feeling better (P = 0.033),
      improved quality of life (P = 0.040), and improved appearance (P = 0.021).
      Testosterone was well tolerated in all patients. CONCLUSIONS: Physiologic
      testosterone administration increases lean body mass and improves quality of life
      among androgen-deficient men with the AIDS wasting syndrome.

PMID- 9652996
TI  - Surgery for recurrent colon cancer: strategies for identifying resectable
      recurrence and success rates after resection. Eastern Cooperative Oncology Group,
      the North Central Cancer Treatment Group, and the Southwest Oncology Group.
AB  - BACKGROUND: Follow-up testing after surgery for colon cancer is recommended
      principally to identify resectable recurrences, but data on the efficacy of,
      outcomes of, and optimal strategies for this testing are limited. OBJECTIVES: To
      determine the relation between follow-up tests and salvage surgery, assess
      outcomes, and document surgical mortality. DESIGN: Retrospective cohort study.
      SETTING: A North American multi-institutional trial comparing postoperative
      chemotherapy plus follow-up with follow-up alone. PATIENTS: 1247 patients with
      resected stage II and stage III colon cancer. INTERVENTION: The protocol mandated
      follow-up testing that could be supplemented at the discretion of treating
      physicians. Indications of recurrent disease were documented. MEASUREMENTS:
      Recurrence, resectable recurrence, surgical mortality, and survival were studied.
      RESULTS: 548 patients had recurrence of colon cancer. Salvage surgery was
      attempted in 222 patients (41%). In 109 patients (20%), curative-intent surgery
      was done for hepatic recurrence (28 patients), pulmonary metastasis (20
      patients), local recurrence (24 patients), or recurrence at other sites (37
      patients). Most curative-intent surgical procedures were motivated by follow-up
      testing (36 patients), elevated carcinoembryonic antigen level (41 patients), or
      symptoms (27 patients). The median follow-up time after curative-intent surgery
      exceeded 5 years; the estimated 5-year disease-free survival rate was 23%. A
      solitary lesion was a favorable prognostic factor. The surgical mortality rate
      was 2%. Curative-intent resections were done in 15 patients with second primary
      colorectal cancer; 12 of these patients have survived disease-free. CONCLUSIONS:
      Second operations for colon cancer that are triggered by follow-up testing or
      symptoms are common and can result in long-term disease-free survival.

PMID- 9652997
TI  - Two cases of severe clinical and histologic hepatotoxicity associated with
      troglitazone.

PMID- 9652998
TI  - Troglitazone-induced hepatic failure leading to liver transplantation. A case
      report.
AB  - BACKGROUND: Troglitazone is a new drug for the treatment of type 2 diabetes.
      Although mild liver injury occurred in 1.9% of participants in controlled trials,
      the U.S. Food and Drug Administration has received reports of five postmarketing
      cases of severe liver disease that resulted in death or liver transplantation.
      OBJECTIVE: To report the clinical and histopathologic characteristics of a
      patient with troglitazone-associated severe liver injury leading to
      transplantation. DESIGN: Case report. SETTING: Two university hospitals. PATIENT:
      A 55-year-old woman taking troglitazone, 400 mg/d, and insulin, 120 U/d.
      INTERVENTION: Discontinuation of troglitazone therapy, pretransplantation liver
      biopsy, and liver transplantation. RESULTS: Early nonspecific symptoms were
      attributed to other causes and were not evaluated. After the patient had used
      troglitazone for 3.5 months, massive loss of liver parenchyma and symptoms of
      liver failure developed, necessitating liver transplantation. CONCLUSION:
      Troglitazone may cause subfulminant liver failure.

PMID- 9652999
TI  - Methods for evaluating the clinical competence of residents in internal medicine:
      a review.
AB  - This paper reviews methods commonly used to assess the clinical competence of
      residents in internal medicine, including the In-Training Examination, medical
      record audits, rating scales, clinical evaluation exercises, and the use of
      standardized patients. Studies were identified through a MEDLINE search (1966 to
      present) and from the bibliographies of relevant articles and were selected for
      inclusion according to consensus between the authors. Whenever possible, original
      studies were chosen over reviews and editorials. No single assessment method can
      successfully evaluate the clinical competence of residents in internal medicine,
      and educators need to be cognizant of the most appropriate applications and the
      advantages and disadvantages of the available evaluation tools. A combination of
      assessment tools provides the best opportunity to evaluate and educate physicians
      in-training.

PMID- 9653000
TI  - Use of cytotoxic agents and cyclosporine in the treatment of autoimmune disease.
      Part 2: Inflammatory bowel disease, systemic vasculitis, and therapeutic
      toxicity.
AB  - When cytotoxic agents were introduced, their ability to disrupt nucleic acid and
      protein synthesis led to their effective use for the treatment of neoplastic
      disease. During the course of this use, however, it became apparent that these
      agents also suppress the immune system. This usually unwelcome effect was
      subsequently studied and beneficially directed toward the treatment of non
      neoplastic diseases in which autoimmune mechanisms were considered important to
      pathogenesis. As a result of these investigations, cytotoxic agents and, more
      recently, cyclosporine have emerged to become an important part of the
      therapeutic regimen for many autoimmune diseases. Nonetheless, these medications
      may still cause treatment-induced illness or even death. It is therefore
      particularly important to weigh the benefits and risks of cytotoxic therapy when
      treating a non-neoplastic disease. This two-part Clinical Staff Conference
      reviews data on the efficacy and toxicity of cytotoxic drugs and cyclosporine in
      selected autoimmune diseases. In part 2, we focus on the role of these agents in
      treating inflammatory bowel disease and systemic vasculitis and review the toxic
      effects of these agents.

PMID- 9653001
TI  - Clinician-educators in academic medical centers: a two-part challenge.
AB  - As academic medical centers increasingly deliver care in primary care settings, a
      new category of faculty-clinician-educators-has emerged. Although the shift of
      education and patient care to outpatient settings makes the expanded role of
      clinician-educators necessary, it also presents challenges to clinician-educators
      themselves and to the institutions for which they work. This article examines
      these contemporary challenges (including financial constraints, undefined
      processes of promotion, and limited opportunities for professional development)
      and suggests strategies for meeting them. The number of clinician-educators
      joining the ranks of medical school faculties will probably continue to increase.
      As clinician-educators seek to provide the highest-quality education and patient
      care in the new medical marketplace, their success will be critical to the
      viability of the academic centers of the future.

PMID- 9653002
TI  - Complementary care: when is it appropriate? Who will provide it?

PMID- 9653003
TI  - The escape.

PMID- 9653004
TI  - Critical pathway for chest pain.

PMID- 9653005
TI  - Body mass and hypertension in women.

PMID- 9653006
TI  - Bronchiolitis obliterans-organizing pneumonia caused by ticlopidine.

PMID- 9653007
TI  - Reversible dysgeusia attributed to losartan.

PMID- 9653008
TI  - Acute intravascular hemolysis after pollen ingestion.

PMID- 9653009
TI  - Electronic cancer Munchausen syndrome.

PMID- 9653010
TI  - New cardiovascular training track: reinventing the wheel?

PMID- 9653011
TI  - Fighting the war on breast cancer: debates over early detection, 1945 to the
      present.

PMID- 9653012
TI  - Congruence between decisions to initiate chiropractic spinal manipulation for low
      back pain and appropriateness criteria in North America.
AB  - BACKGROUND: Recent U.S. practice guidelines recommend spinal manipulation for
      some patients with low back pain. If followed, these guidelines are likely to
      increase the number of persons referred for chiropractic care. Concerns have been
      raised about the appropriate use of chiropractic care, but systematic data are
      lacking. OBJECTIVE: To determine the appropriateness of chiropractors' decisions
      to use spinal manipulation for patients with low back pain. DESIGN: Retrospective
      review of chiropractic office records against preset criteria for appropriateness
      that were developed from a systematic review of the literature and a nine-member
      panel of chiropractic and medical specialists. Appropriateness criteria reflect
      the expected balance between risk and benefit. SETTING: 131 of 185 (71%)
      chiropractic offices randomly sampled from sites in the United States and Canada.
      PATIENTS: 10 randomly selected records of patients presenting with low back pain
      from each office (1310 patients total). MEASUREMENTS: Sociodemographic data on
      patients and chiropractors; use of health care services by patients; assessment
      of the decision to initiate spinal manipulation as appropriate, uncertain, or
      inappropriate. RESULTS: Of the 1310 patients who sought chiropractic care for low
      back pain, 1088 (83%) had spinal manipulation. For 859 of these patients (79%),
      records contained data sufficient to determine whether care was congruent with
      appropriateness criteria. Care was classified as appropriate in 46% of cases,
      uncertain in 25% of cases, and inappropriate in 29% of cases. Patients who did
      not undergo spinal manipulation were less likely to have a presentation judged
      appropriate and were more likely to have a presentation judged inappropriate than
      were patients who did undergo spinal manipulation (P = 0.01). CONCLUSIONS: The
      proportion of chiropractic spinal manipulation judged to be congruent with
      appropriateness criteria is similar to proportions previously described for
      medical procedures; thus, the findings provide some reassurance about the
      appropriate application of chiropractic care. However, more than one quarter of
      patients were treated for indications that were judged inappropriate. The number
      of inappropriate decisions to use chiropractic spinal manipulation should be
      decreased.

PMID- 9653013
TI  - 5th Congress of the International Society for Rotary Blood Pumps. Marseille,
      France, September 10-12, 1997. Abstracts.

PMID- 9653014
TI  - Candida onychomycosis in HIV infection.
AB  - Primary nail invasion by Candida is uncommon and almost exclusively seen in
      patients with an impaired immune function. The appearance of Candida
      onychomycosis in an adult who is not under immunosuppressive treatment always
      requires a laboratory evaluation of the immunologic function including HIV
      assays. We report 2 cases of distal subungual onychomycosis due to Candida sp. in
      HIV. In one of our patients, the diagnosis of Candida onychomycosis preceded the
      diagnosis of advanced HIV infection. In both of our patients treatment with
      systemic antifungals produced complete cure of Candida onychomycosis and the 1
      year follow-up did not reveal any relapse of the onychomycosis.

PMID- 9653015
TI  - Occurrence rates of HLA-DRB1, HLA-DQB1, and HLA-DPB1 alleles in patients
      suffering from vitiligo.
AB  - By investigating a group of 39 unrelated adults suffering from vitiligo it was
      found that alleles HLA-DRB1*0701, -DQB1*0201, and -DPB1*1601 differed in their
      frequencies in comparison to those observed in the healthy population. The allele
      HLA-DRB1*0701 was found in 26.5% of patients compared to 14.2% in the healthy
      group (p < 0,01, RR = 2.17). The allele HLA-DQB1*0201 was present in 33.8% of
      patients compared to 21.2% (p < 0,025, RR = 1.89). The allele HLA-DPB1*1601 was
      found in 6.41% of patients compared to 2.05% in the healthy group (p < 0.05, RR =
      3.3). No other significant deviations in the frequencies of investigated alleles
      were observed.

PMID- 9653016
TI  - Characterisation of glucocorticoid receptors in peripheral blood leukocytes of
      Carp, Cyprinus carpio L.
AB  - Binding studies with [3H]cortisol revealed the presence of a single class of
      cortisol-binding sites on carp peripheral blood leukocytes (PBL). These binding
      sites showed high affinity (Kd of 3.8 nM) and low capacity (490 binding sites per
      cell), indicative of receptor binding. Affinity for cortisone was 254-fold lower
      than for cortisol. Affinity for the two synthetic glucocorticoids dexamethasone
      and triamcinolone acetonide (TA) was 4- and 10-fold higher than for cortisol,
      respectively. Further evidence for the GR character of the receptor came from
      results showing that cortisol induced apoptosis, which could be blocked by the
      glucocorticoid analogue RU486. A single meal of cortisol-containing food elevated
      plasma cortisol concentrations and decreased GR density in PBL, as measured 3 h
      later. The percentage of circulating B lymphocytes also decreased. Cortisol
      induced redistribution of B lymphocytes from the blood, due to cortisol
      treatment, may explain the decrease of GR numbers in PBL, although downregulation
      of available GR remains possible.

PMID- 9653017
TI  - Loss of glucose transporter-2 precedes insulin loss in the nonobese diabetic and
      the low-dose streptozotocin mouse models: a comparative immunohistochemical study
      by light and confocal microscopy.
AB  - Glucose transporter-2 (glut2) is underexpressed in beta cells of several rodent
      models of non-insulin-dependent diabetes mellitus (NIDDM). This may also be true
      for rodent models of insulin-dependent diabetes mellitus (IDDM). The present
      study examines two murine models of autoimmune IDDM, the nonobese diabetic (NOD)
      and the low-dose streptozotocin (stz) murine models for changes in the expression
      of glut2 by double-label light and confocal microscopy during various stages of
      the disease. The spatial distribution of glut2 cells was also examined in
      relation to insulin immunoreactive cells and the islet inflammatory cells during
      these stages. In both the female NOD mouse and the female Swiss mouse without stz
      treatment, glut2 colocalized with insulin in virtually all the beta cells. In the
      NOD mouse, islets with moderate to advanced insulitis showed either an absence or
      considerably reduce expression of glut2 in insulin-containing beta cells. Cells
      with reduced glut2 expression were usually located adjacent to the region of
      insulitis. At onset of diabetes, glut2 immunolabeling was reduced despite the
      preservation of weak insulin immunoreactivity. In Swiss mice treated repeatedly
      with stz, glut2 labeling began to decline in select Beta cells after the fourth
      injection in approximately 50% of the islets, despite the lack of insulitis. At
      this stage expression of glut2 fell in a small number of islets with evidence of
      early macrophage infiltration. Loss of glut2 became more pronounced in
      nondiabetic Swiss mice after the fifth injection. At this stage glut2 labeling in
      the plasma membrane appeared diffuse and variable. At onset of stz-induced
      diabetes, glut2 expression significantly fell, despite weak immunoreactivity for
      insulin. This loss was associated with an enhanced influx of both macrophages and
      T lymphocytes within the islets of diabetes mice. In both the NOD and the low
      dose stz mouse models, loss of glut2 thus occurs from an early stage and precedes
      hyperglycaemia. This loss may be mediated by immune and nonimmune mechanisms.

PMID- 9653018
TI  - GLUT-4 Deficiency and severe peripheral resistance to insulin in the teleost fish
      tilapia.
AB  - Teleost fish, in general, are glucose intolerant; this trait has been attributed
      to piscine islets secreting insulin primary in response to amino acid
      secretogogues rather than glucose. However, pancreatic islet from the teleost
      fish tilapia, when transplanted into diabetic nude mice, were glucose responsive
      even though tilapia were severely glucose intolerant. This suggested a strong
      peripheral resistance to the glucostatic effects of insulin. Using Western
      blotting with polyclonal antibodies as well as Northern analysis for mRNA,
      tilapia tissues were found to be devoid of GLUT-4, the insulin-sensitive glucose
      transporter responsible for the hypoglycemic effect of insulin in mammals. The
      absence of GLUT-4 in peripheral tissues may explain why tilapia, and possibly
      other teleost fish, are severely glucose intolerant. This suggests that tilapia
      islets have evolved along mammalian lines to be glucose sensitive while tilapia
      peripheral tissue have diverged widely. Using the same methods, tilapia were
      found to have a very limited tissue distribution of the insulin-independent
      glucose transporter, GLUT-1, which is responsible for basal glucose transport in
      mammalian cells. It is suggested that tilapia provide a naturally occurring GLUT
      4 knockout model.

PMID- 9653019
TI  - Immunological cross-reactivity between rainbow trout GTH I and GTH II and their
      alpha and beta subunits: application to the development of specific
      radioimmunoassays.
AB  - Immunological cross-reactivities between rainbow trout GTH I and GTH II and their
      alpha and beta have been studied using highly purified rainbow trout
      gonadotropins and subunits and antibodies raised against beta subunits. From
      these observations radioimmunoassays have been developed for rainbow trout GTH I
      and GTH II. The GTH II RIA was highly specific and cross-reacted only with GTH II
      and its beta 1 subunits, with beta 2 being less potent than beta 1 in competing
      GTH II binding. There was no cross-reactivity with GTH I. Its sensitivity varied
      between 0.1 and 0.2 ng/ml, allowing GTH II measurement early in the reproductive
      cycle. Variations between and within assays were less than 10%. There was a lack
      of specificity of GTH I RIA (44% cross-reactivity with GTH II, when using
      labelled native GTH I). Reasons for this lack of sensitivity were studied. It
      cannot be attributed to beta subunits (less than 1.2% cross-reactivity). However,
      the cross-reactivity of alpha subunits was very important. This suggests that the
      presence of free alpha subunits in the medium can be responsible for the lack of
      specificity. Labelling native GTH I resulted in conformational change in
      molecular weight and dissociation of the hormone into subunits, whereas
      iodination did not induce GTH II dissociation. This dissociation can be avoided
      by labelling the stable form of GTH I. Using this radio-tracer, the specificity
      and the sensitivity of the assay were greatly improved (GTH II cross-reactivity
      was decreased to 3.7, mean sensitivity 0.87 +/- 0.072 ng/ml). The sensitivity of
      the assay diminished with ageing of labelled GTH I. The assay variation was 4.6%
      within an assay and 9.8% between assays. The use of labelled beta GTH I still
      increases the specificity (2.3% GTH II cross-reactivity), but with a 2.4-fold
      loss of sensitivity. In both GTH I and GTH II RIA plasma and spiked plasma with
      purified GTHs gave displacement curves parallel to standard. These assays were
      used to study pituitary responsiveness to a GnRH analogue in female rainbow trout
      prior to oocyte maturation. The effects of GnRH on GTH II secretion were
      confirmed. The peptide did not significantly stimulate GTH I secretion.

PMID- 9653020
TI  - GTH I and GTH II secretion profiles during the reproductive cycle in female
      rainbow trout: relationship with pituitary responsiveness to GnRH-A stimulation.
AB  - The recent purification of two gonadotropins, GTH I and GTH II, in teleost fish
      and the development of their specific radioimmunoassays using antibodies directed
      against their beta subunits have demonstrated that earlier assays for GTH II also
      measured GTH I. Most of the results on the gonadotropic control of reproduction
      in fish must thus be reinvestigated using specific assays for each gonadotropin.
      The present investigation examines changes in blood plasma levels of GTH I and
      GTH II during the annual reproductive cycle of rainbow trout in relation to the
      ability of gonadotropin-releasing hormone (GnRH) to stimulate in vivo GTH I and
      GTH II secretion, with focus on the periovulatory period. GTH I was detected from
      immature to postovulatory stages, with a significant increase at the onset of
      exogenous vitellogenesis, with GTH I levels rising from 7.83 +/- 3.37 to 16.87 +/
      4.52 ng/ml. GTH II remained very low until the end of the vitellogenesis. For
      both hormones, the most significant variations were measured during the
      periovulatory period. GTH II levels peaked on the day of maturation, but the
      increase was biphasic with a first peak arising 4 days prior to maturation. This
      evaluation of GTH II was preceded by a progressive and significant rise GTH I
      levels starting from 5.83 +/- 2.17 ng/ml 8 days before maturation and increasing
      to more than 10 ng/ml on the day of maturation. Thus, the GTH II maturation surge
      is not the only gonadotropic signal occurring before ovulation. The role of the
      preovulatory GTH I increase remains unknown. After ovulation the secretory
      profiles of the two hormones depended on the presence of absence of ovulated eggs
      in the body cavity. There was a major increase in GTH I levels starting 4 days
      after ovulation and egg stripping, reaching more than 25 ng/ml. Conversely, in
      these fish the GTH II levels gradually decreased. In the fish which kept their
      eggs in the body cavity the progress was reversed; 8 days after maturation, GTH
      II increased to levels similar to those measured prior to maturation; the
      presence of the eggs prevented an increase in GTH I. This seems to indicate that
      postovulatory regulation of GTH I and GTH II secretion might involve ovarian
      factors that act in an antagonistic fashion. The prevention of the increase in
      GTH I levels in the presence of eggs suggests that as long as eggs are present in
      the body cavity, the development of a new cycle of gametogenesis is not possible,
      since GTH I is the gonadotropin mainly involved in controlling this phenomena.
      GnRH cannot significantly stimulate GTH I secretion at any stage of
      gametogenesis, even when its levels increased after ovulation. Other factors
      antagonizing GnRH are involved. The well-known antagonistic effect of dopamine on
      the GnRH stimulated GTH II secretion is fish is not involved since the dopamine
      antagonist, pimozide, was ineffective in inducing a stimulatory action of GnRH on
      GTH I secretion. Although GnRH can stimulate GTH II secretion from mid
      vitellogenesis, the response to GnRH was not correlated with GTH II in blood.
      These results suggest that GTH I and GTH II secretions are regulated by different
      mechanisms and different factors.

PMID- 9653021
TI  - Cloning of a full-length insulin-like growth factor-I complementary DNA in the
      goldfish liver and ovary and development of a quantitative PCR method for its
      measurement.
AB  - Five forms of insulin-like growth factor-I (IGF-I) complementary DNA (cDNA) were
      isolated by PCR from goldfish liver and ovary, using primers based on common carp
      IGF-I sequence. In the goldfish liver, we cloned and sequenced three IGF-I forms
      (1,2, and 3), and elucidated the full-length cDNA sequence using the 5'-and 3'
      RACE. Two IGF-I forms (1 and 2) were cloned from the goldfish ovary and were
      found to have differences with respect to both size and nucleotide sequence
      compared to liver IGF-I. The entire liver IGF-I form 1 sequence was found to be
      833 nucleotides long, containing a 483-nucleotide open reading from encoding 161
      amino acids. The deduced amino acid sequence of the mature peptide was compared
      to IGF-I sequences of other vertebrates, and found to have 97 and 93% similarity
      to carp and salmon IGF-I, respectively, In this study we also developed a
      competitive quantitative PCR method and demonstrated an increase in IGF-I
      expression following treatments with growth hormone or gonadotropin-releasing
      hormone in the goldfish liver.

PMID- 9653022
TI  - Cloning and sequence analysis of a pituitary prolactin cDNA from the brushtail
      possum (Trichosurus vulpecula).
AB  - Overlapping cDNA partial clones of pituitary prolactin from the marsupial
      brushtail possum (Trichosurus vulpecula) were isolated and sequenced. The
      nucleotide and deduced amino acid sequences showed high sequence identity with
      pig prolactin (84.3 and 92.5%, respectively) and all of the expected structural
      features of a quadruped prolactin. A prolactin gene tree was constructed and
      rates of evolution calculated for possum along with several mammalian and
      nonmammalian prolactins. Possum prolactin was most closely linked to the
      prolactins of eutherian mammals but branched from the main mammalian line well
      before the eutherian prolactins. The prolactin/GH family shows variable rates of
      evolution ranging from 0.3 substitutions/amino acid site/year x 10(9) for pig
      prolactin to 7.0 substitutions/ amino acid site/year x 10(9) for the mouse. Since
      divergence from the eutherian mammals, possum prolactin has shown a slow rate of
      evolution (0.2 substitutions/ amino acid site/year x 10(9)). As expected, the
      prolactin gene was expressed in the possum pituitary gland but not in the liver,
      lung, kidney, heart, or mammary gland.

PMID- 9653023
TI  - cDNA cloning of growth hormone from the brushtail possum (Trichosurus vulpecula).
AB  - The full-length nucleotide sequence for the cDNA of growth hormone (GH) from the
      marsupial brushtail possum (Trichosurus vulpecula) was determined using reverse
      transcription followed by polymerase chain reaction (RT-PCR) and the 5'/3' rapid
      amplification of cDNA ends (RACE) technique. Sequence information showed that the
      possum GH cDNA was 831 base pairs (bp) in length, including the 5'untranslated
      region (60 bp), the signal peptide (75 bp), the mature protein (573 bp, including
      stop codon), and the 3' untranslated region (123 bp). At both the nucleotide and
      the amino acid level (deduced from nucleotide sequence), there was a high degree
      of sequence identity with pig and horse. These species were similar at 82.8 and
      83.0% of bases at the nucleotide level and 91.6 and 91.1% at the amino acid
      level, respectively. Northern analysis showed that GH mRNA is present in the
      pituitary gland and was similar in size to that seen in other mammals
      (approximately equal to 0.9 kb). Analysis of molecular evolution of GH in the
      possum indicated that the rate of evolution is relatively slow (0.4
      substitutions/ amino acid site/year x 10(9) and typical of that seen for
      nonprimate mammals, which exhibit rates ranging between 0.2 and 1.3
      substitutions/amino acid site/year x 10(9).

PMID- 9653024
TI  - Effects of light on plasma somatolactin levels in red drum (Sciaenops ocellatus).
AB  - The effects of illumination on circulating somatolactin (SL) levels were studied
      in red drum sampled at various times during a 24-h light-dark cycle (l2L:l2D) and
      during a 24-h period of constant light. Plasma SL concentrations were low in red
      drum sampled during the light phase (0.6 +/- 0.05-1.1 +/- 0.2 ng/ml). The levels
      were significantly elevated during the early-dark phase (5.8 +/- 1.0 ng/ml) and
      declined during the late-dark phase (0.39 +/- 0.05 ng/ml). In contrast, plasma SL
      levels remained low. (0.4 +/- 0.1-1.3 +/- 0.4 ng/ml) in fish sampled through a 24
      h constant light period following a 1-week exposure to the light-dark cycle.
      Circulating SL levels were also significantly elevated during the early-dark
      phase in fish maintained under a reversed light-dark cycle. The role of the eyes
      in mediation the SL response to light was evaluated by comparing circulating SL
      levels in optic-tract sectioned and enucleated fish with those of intact
      (control) fish. Plasma SL concentrations were significantly higher in optic-tract
      sectioned and enucleated fish (6.5 +/- 0.9-13.8 +/- 1.5 ng/ml) than in control
      fish (0.6 +/- 0.05-3.9 +/- 0.7 ng/ml) during both the early-dark phase and the
      early-light phase of the 24-h light-dark cycle. The absence of significant
      changes in plasma SL levels between the light and dark phases in optic-tract
      sectioned and enucleated fish appears to be due to a loss of light perception in
      these fish. Moreover, intact and sham-operated red drum maintained in constant
      darkness had dramatically increased plasma SL levels (18.8 +/- 2.0-24.8 +/- 1.8
      ng/ml). The present results are consistent with our earlier findings that plasma
      SL levels are elevated in fish kept in constant darkness and in a dark-background
      tank (reduction in overall light levels) during the light phase. Taken together,
      these results suggest that plasma SL levels are elevated in red drum in the
      absence of light and in response to low illumination. Interestingly, the
      integument of the fish became light during the dark phase of the light-dark
      cycle. In our earlier studies, the increase of plasma SL concentrations was
      associated with aggregation of melanophores, and direct effects of SL on
      melanophore aggregation were demonstrated. Overall, our studies with red drum
      suggest a possible role of elevated SL levels on melanophore aggregation during
      the dark phase of the 24-h day-night cycle.

PMID- 9653025
TI  - Immunochemical identification of thyrotropes and gonadotropes in the pars
      distalis and pars tuberalis of the toad (Bufo boreas) with reference to ontogenic
      changes.
AB  - Morphologically distinct secretory cells in the pituitary pars distalis and pars
      tuberalis of larval and adult toads (Bufo boreas) immunoreactive cells in the
      pars distalis. Thyrotropin immunoactivity appears in pars tuberalis and pars
      distalis before gonadotropin immunoreactivity during early development. Antisera
      which distinguish gonadotropes (stained with human and sea turtle LH beta) and
      thyrotropes (stained with human TSH beta) as separate cell types in the pars
      distalis of the adult toad immunoreact with the same single type of cell in the
      pars distalis of the tadpole up through metamorphosis, suggesting the existence
      of a single pluripotent, glycoprotein-producing precursor cell early in
      development. Gonadotropin antisera do not react with the pars tuberalis in
      tadpoles or adults.

PMID- 9653026
TI  - Multiple forms of GnRH are released from perifused medial basal
      hypothalamic/preoptic area (MBH/POA) explants in birds.
AB  - Both chicken gonadotropin-releasing hormones I and II (cGnRH I and II) were
      detected in abundant quantity by radioimmunoassay of extracts of Japanese quail
      medial basal hypothalamic/preoptic area (MBH/POA) fragments that included the
      median eminence (ME) region. However, in radioimmunoassayed extracts of Japanese
      quail ME alone, the concentration of cGnRH I greatly exceeded that of cGnRH II
      (approximately 450 pg/ME vs < 10 pg/ME). Likewise, cGnRH I and II were released
      into perifusates from quail an turkey MBH/POA explants maintained in short-term
      perifusion. Release of both forms occurred whether or not explants included the
      ME region, i.e., from quail POA explants did not include the ME or from turkey
      MBH/POA explants from which the ME region had been dissected out. This indicates
      that neuropeptides released from areas other than the ME can be a major source of
      neuropeptides detected in perifusates. Further, release of cGnRH I was altered
      following the addition of norepinephrine to perfusion media, whereas cGnRH II
      release was unaffected, again, whether or not explants included the ME. These
      results demonstrate that the release of neurohemoral substances from perifused
      explants cannot be assumed to represent regulated secretion from the ME.

PMID- 9653027
TI  - Anatomy of hot spots in protein interfaces.
AB  - Binding of one protein to another is involved in nearly all biological functions,
      yet the principles governing the interaction of proteins are not fully
      understood. To analyze the contributions of individual amino acid residues in
      protein-protein binding we have compiled a database of 2325 alanine mutants for
      which the change in free energy of binding upon mutation to alanine has been
      measured (available at http://motorhead. ucsf.edu/thorn/hotspot). Our analysis
      shows that at the level of side-chains there is little correlation between buried
      surface area and free energy of binding. We find that the free energy of binding
      is not evenly distributed across interfaces; instead, there are hot spots of
      binding energy made up of a small subset of residues in the dimer interface.
      These hot spots are enriched in tryptophan, tyrosine and arginine, and are
      surrounded by energetically less important residues that most likely serve to
      occlude bulk solvent from the hot spot. Occlusion of solvent is found to be a
      necessary condition for highly energetic interactions.

PMID- 9653028
TI  - Termination of packaging of the bacteriophage lambda chromosome: cosQ is required
      for nicking the bottom strand of cosN.
AB  - Termination of packaging of the lambda chromosome involves completion of
      translocation of the DNA into the head shell, and conversion of the translocation
      complex into a cleavage complex. The cleavage reaction introduces staggered nicks
      into the downstream cosN to generate the right cohesive end of the chromosome.
      cosQ, a site adjacent to cosN, was found to be required for nicking the bottom
      strand of cosN; bottom strand nicking was also sequence-specific for bps at the
      nick site. Nicking of the top strand of cosN (cosNL) was stimulated by cosQ, but
      fidelity and efficiency of cosNL nicking were largely dictated by other cos
      subsites (i.e. cosB and I2). Aberrant top-strand cleavage within cosQ was
      observed in the absence of I2, and nicking at a site 8 nt 5' to the normal cosNL
      nick site occurred in the absence of cosB. The presence of cosQ was found to be
      insufficient to arrest DNA translocation in vivo, indicating that cosQ, per se,
      is not a packaging stop signal. A model is presented in which the role of cosQ is
      to depolarize the asymmetric arrangement of terminase protomers in the
      translocation complex so that protomers are configured to match the 2-fold
      rotational symmetry of cosN.

PMID- 9653029
TI  - Sequence specificity of bacteriophage 434 repressor-operator complexation.
AB  - The binding affinity of the bacteriophage 434 repressor for its DNA operator
      depends strongly on the nature of two central base-pairs that are not in contact
      with the dimeric protein. In order to investigate the origin of this sequence
      specificity, we carried out molecular modelling of five model operators with
      central TA, AT, CG, GC and IC sequences. The five oligomers were studied both
      before and after complexation with the N-terminal binding domain of the 434
      repressor. The relative importance of nucleic acid flexibility on operator
      repressor binding was studied via a low frequency normal mode analysis using an
      internal coordinate method that we developed recently. The results suggest a
      higher twisting flexibility for TA and AT central steps than for CG, GC or IC
      steps, but the differences appear to be too small to account for the strength of
      repressor binding. An energetic analysis of the model operator-repressor
      complexes reveals rather that the preference for A.T and T.A base-pairs is
      electrostatic in origin and is linked to the presence of cationic Arg43 side
      chains of repressor. This conclusion is supported by comparison with an R43A
      mutant and correlates with the sequence dependence of the electrostatic potential
      in the central minor groove of the operators.

PMID- 9653030
TI  - Polymer chain statistics and conformational analysis of DNA molecules with bends
      or sections of different flexibility.
AB  - The worm-like chain model has often been employed to describe the average
      conformation of long, intrinsically straight polymer molecules, including DNA.
      The present study extends the applicability of the worm-like chain model to
      polymers containing bends or sections of different flexibility. Several cases
      have been explicitly considered: (i) polymers with a single bend; (ii) polymers
      with multiple coplanar bends; (iii) polymers with two non-coplanar bends; and
      (iv) polymers comprised of sections with different persistence lengths.
      Expressions describing the average conformation of such polymers in terms of the
      mean-square end-to-end distance have been derived for each case. For cases (i)
      and (iv), expressions for the projection of the end-to-end vector onto the
      initial orientation of the chain are presented. The expressions derived here have
      been used to investigate DNA molecules with sequence-induced bending (A-tracts).
      Mean-square end-to-end distance values determined from a large number of A-tract
      containing DNA molecules visualized by scanning force microscopy resulted in an
      average bend angle of 13.5 degrees per A-tract. A similar study was performed to
      characterize the flexibility of double-strandedDNA molecules containing a single
      stranded region. Analysis of their mean-square end-to-end distance yielded a
      persistence length of 1.3 nm for single-stranded DNA.

PMID- 9653031
TI  - Structure and dynamics of supercoil-stabilized DNA cruciforms.
AB  - Understanding DNA function requires knowledge of the structure of local, sequence
      dependent conformations that can be dramatically different from the B-form helix.
      One alternative DNA conformation is the cruciform, which has been shown to have a
      critical role in the initiation of DNA replication and the regulation of
      transcription in certain systems. In addition, cruciforms provide a model system
      for structural studies of Holliday junctions, intermediates in homologous DNA
      recombination. Cruciforms are not thermodynamically stable in linear DNA due to
      branch point migration, which makes their study using many biophysical techniques
      problematic. Atomic Force Microscopy (AFM) was applied to visualize cruciforms in
      negatively supercoiled plasmid DNA. Cruciforms are seen as clear-cut extrusions
      on the DNA filament with the lengths of the arms consistent with the size of the
      hairpins expected from a 106 bp inverted repeat. The cruciform exists in two
      different conformations, an extended one with the angle of ca. 180 degrees
      between the hairpin arms and a compact, X-type conformation, with acute angles
      between the hairpin arms and the main DNA strands. The ratio of molecules with
      the different conformations of cruciforms depends on ionic conditions. In the
      presence of high salt or Mg cations, a compact, X-type conformation is highly
      preferable. Remarkably, the X-conformation was highly mobile allowing the
      cruciform arms to adopt a parallel orientation. The structure observed is
      consistent with a model of the Holliday junction with a parallel orientation of
      the exchanging strands.

PMID- 9653032
TI  - Localization and characterization of the dimerization domain of holliday
      structure resolving endonuclease VII of phage T4.
AB  - Endonuclease VII (Endo VII) is a Holliday structure resolving enzyme of
      bacteriophage T4. Its nucleolytic activity depends on subactivities, which in
      order of execution are: (i) dimerization, (ii) binding to DNA, (iii) and cleavage
      of DNA. In an effort to assign these subfunctions to the primary sequence of the
      protein, a series of spontaneous point mutations deficient in DNA cleavage was
      isolated. Some of these mutations affected the dimerization of Endo VII. Compared
      with wild-type protein, which dimerizes completely in solution, more than 95% of
      one of the mutant proteins (W87R) remained in the monomeric state. Only the
      dimeric fraction of this protein bound to DNA. The dimerization domain of Endo
      VII was mapped by truncating the gene from both ends and analysing the
      dimerization ability of the purified peptides by crosslinking with
      glutaraldehyde. The dimerization domain was thus determined to reside between
      amino acid residues 55 and 105. Computer analyses predicted two alpha-helices (H2
      and H3) in this section of the protein. As demonstrated by heterodimer formation,
      two copies of helix H3, but only one copy of helix H2, are required for
      dimerization. Helical wheel analyses revealed that both helices expose a
      hydrophobic face along their axes, suggesting that hydrophobic interaction
      between helices H3 mediate formation of Endo VII dimers, while helices H2
      stabilize them.

PMID- 9653033
TI  - Disulfide analysis reveals a role for macrophage migration inhibitory factor
      (MIF) as thiol-protein oxidoreductase.
AB  - The molecular mechanism of action of macrophage migration inhibitory factor
      (MIF), a cytokine with a critical role in the immune and inflammatory response,
      has not yet been identified. Here we report that MIF can function as an enzyme
      exhibiting thiol-protein oxidoreductase activity. Using a decapeptide fragment of
      MIF (MF1) spanning the conserved cysteine sequence motif Cys57-Ala-Leu-Cys60
      (CALC), Cys-->Ser mutants (C57S MIF, C60S MIF, and C57S/C60S MIF) of human MIF
      (wtMIF), and alkylated wtMIF, we show that this activity is mediated by the CALC
      region and is important for the macrophage-activating properties of MIF. Both
      wtMIF and MF1 were demonstrated to form an intramolecular disulfide bridge. Using
      two common oxidoreductase assays, MIF was shown to enzymatically catalyze the
      reduction of insulin and 2-hydroxyethyldisulfide (HED). Examination of wtMIF and
      the mutants by far-UV circular dichroism spectroscopy (CD) together with
      denaturation studies showed that substituting or reducing the cysteine residues
      of CALC led to a reduced conformational stability of MIF but did not
      significantly change its overall conformation. A functional role for the CALC
      region was revealed by subjecting the mutants and alkylated wtMIF to the
      enzymatic assays. Mutant C60S did not have any enzymatic activity while mutant
      C57S had a reduced activity. Thiol-modified wtMIF that was alkylated under
      oxidizing conditions was found to have full enzymatic activity, whereas
      alkylation of wtMIF under reducing conditions completely eliminated MIF-mediated
      redox activity. Importantly, further physiological relevance of the disulfide
      motif was obtained by examining the mutants and alkylated MIF in an immunological
      assay that involved the macrophage-activating properties of MIF. In this test,
      mutant C60S was essentially inactive and mutant C57S was partly active,
      indicating together that at least some of the cytokine-like biological activities
      of MIF are dependent on the presence of cysteine 57 and 60. Again, use of the
      alkylated MIF species confirmed the role of the cysteine motif for this MIF
      activity. In conclusion, our results argue (a) that MIF exhibits enzymatic
      oxidoreductase activity, (b) that this activity is dependent on the presence of
      the catalytic center that is formed by cysteine residues 57 and 60, and (c) that
      certain MIF-mediated immune processes are due to the cysteine-mediated redox
      mechanism.

PMID- 9653034
TI  - Escherichia coli 70 S ribosome at 15 A resolution by cryo-electron microscopy:
      localization of fMet-tRNAfMet and fitting of L1 protein.
AB  - Cryo-electron microscopy of the ribosome in different binding states with mRNA
      and tRNA helps unravel the different steps of protein synthesis. Using over
      29,000 projections of a ribosome complex in single-particle form, a three
      dimensional map of the Escherichia coli 70 S ribosome was obtained in which a
      single site, the P site, is occupied by fMet-tRNAfMet as directed by an AUG codon
      containing mRNA. The superior resolution of this three-dimensional map, 14.9 A,
      has made it possible to fit the tRNA X-ray crystal structure directly and
      unambiguously into the electron density, thus determining the locations of
      anticodon-codon interaction and peptidyltransferase center of the ribosome.
      Furthermore, at this resolution, one of the distinctly visible domains
      corresponding to a ribosomal protein, L1, closely matches with its X-ray
      structure.

PMID- 9653035
TI  - Expression of an antibody fragment at high levels in the bacterial cytoplasm.
AB  - Recombinant antibody fragments expressed in the cytoplasm of cells have
      considerable practical potential. However in the reducing environment of the
      cytoplasm, the intradomain disulphide bonds are not formed and the fragments are
      unstable and expressed in low yields. Here we attempted to overcome these
      limitations. We first isolated an antibody single chain Fv fragment that binds
      and activates an inactive mutant beta-galactosidase. We then subjected the gene
      encoding the scFv fragment to random mutation in vitro by error-prone polymerase
      chain reaction, and co-expressed the mutant beta-galactosidase and mutant
      antibody fragments in lac- bacteria. By plating on limiting lactose, we selected
      for antibody mutants with improved expression, and after four successive rounds
      of mutation and selection, isolated an antibody fragment that is expressed in the
      bacterial cytoplasm with yields of 0.5 g/l in a shaker flask (A600 nm of 5.5) and
      3.1 g/l (A600 nm=33) in a fermentor. Analysis of the mutant antibody fragments
      revealed that the disulphide bonds are reduced in the cytoplasm, and that the
      fragments could be denatured and renatured efficiently under reducing conditions
      in vitro. This shows that with a suitable method of screening or selection, it is
      possible to make folded and functional antibody fragments in excellent yield in
      the cytoplasm.

PMID- 9653036
TI  - Refined structure of Cro repressor protein from bacteriophage lambda suggests
      both flexibility and plasticity.
AB  - The structure of the Cro repressor protein from phage lambda has been refined to
      a crystallographic R-value of 19.3% at 2.3 A resolution. The re fined model
      supports the structure as originally described in 1981 and provides a basis for
      comparison with the Cro-operator complex described in the accompanying paper.
      Changes in structure seen in different crystal forms and modifications of Cro
      suggest that the individual subunits are somewhat plastic in nature. In addition,
      the dimer of Cro suggests a high degree of flexibility, which may be important in
      forming the Cro-DNA complex. The structure of the Cro subunit as determined by
      NMR agrees reasonably well with that in the crystals (root-mean-square
      discrepancy of about 2 A for all atoms). There are, however, only a limited
      number of intersubunit distance constraints and, presumably for this reason, the
      different NMR models for the dimer vary substantially among themselves
      (discrepancies of 1.3 to 5.5 A). Because of this variation it is not possible to
      say whether the range of discrepancies between the X-ray and NMR Cro dimers (2.9
      to 7.5 A) represent a significant difference between the X-ray and solution
      structures. It has previously been proposed that substitutions of Tyr26 in Cro
      increase thermal stability by the "reverse hydrophobic effect", i.e. by exposing
      40% more hydrophobic surface to solvent in the folded form than in the unfolded
      state. The refined structure, however, suggests that Tyr26 is equally solvent
      exposed in the folded and unfolded states. The most stabilizing substitution is
      Tyr26-->Asp and in this case it appears that interaction with an alpha-helix
      dipole is at least partly responsible for the enhanced stability.

PMID- 9653037
TI  - Crystal structure of lambda-Cro bound to a consensus operator at 3.0 A
      resolution.
AB  - The structure of the Cro protein from bacteriophage lambda in complex with a 19
      base-pair DNA duplex that includes the 17 base-pair consensus operator has been
      determined at 3.0 A resolution. The structure confirms the large changes in the
      protein and DNA seen previously in a crystallographically distinct low-resolution
      structure of the complex and, for the first time, reveals the detailed
      interactions between the side-chains of the protein and the base-pairs of the
      operator. Relative to the crystal structure of the free protein, the subunits of
      Cro rotate 53 degrees with respect to each other on binding DNA. At the same time
      the DNA is bent by 40 degrees through the 19 base-pairs. The intersubunit
      connection includes a region within the protein core that is structurally
      reminiscent of the "ball and socket" motif seen in the immunoglobulins and T-cell
      receptors. The crystal structure of the Cro complex is consistent with virtually
      all available biochemical and related data. Some of the interactions between Cro
      and DNA proposed on the basis of model-building are now seen to be correct, but
      many are different. Tests of the original model by mutagenesis and biochemical
      analysis corrected some but not all of the errors. Within the limitations of the
      crystallographic resolution it appears that operator recognition is achieved
      almost entirely by direct hydrogen-bonding and van der Waals contacts between the
      protein and the exposed bases within the major groove of the DNA. The
      discrimination of Cro between the operators OR3 and OR1, which differ in sequence
      at just three positions, is inferred to result from a combination of small
      differences, both favorable and unfavorable. A van der Waals contact at one of
      the positions is of primary importance, while the other two provide smaller,
      indirect effects. Direct hydrogen bonding is not utilized in this distinction.

PMID- 9653038
TI  - Crystal structure of the ternary complex of E. coli purine nucleoside
      phosphorylase with formycin B, a structural analogue of the substrate inosine,
      and phosphate (Sulphate) at 2.1 A resolution.
AB  - The ternary complex of purine nucleoside phosphorylase from E. coli with formycin
      B and a sulphate or phosphate ion crystallized in the hexagonal space group P6122
      with unit cell dimensions a=123.11, c=241.22 A and three monomers per asymmetric
      unit. The biologically active hexamer is formed through 2-fold crystallographic
      symmetry, constituting a trimer of dimers. High-resolution X-ray diffraction data
      were collected using synchrotron radiation (Daresbury, England). The crystal
      structure was determined by molecular replacement and refined at 2.1 A resolution
      to an R-value of 0.196. There is one active centre per monomer, composed of
      residues belonging to two subunits of one dimer. The phosphate binding site is
      strongly positively charged and consists of three arginine residues (Arg24, Arg87
      and Arg43 from a neighbouring subunit), Ser90 and Gly20. It is occupied by a
      sulphate or phosphate anion, each oxygen atom of which accepts at least two
      hydrogen bonds or salt-bridges. The sulphate or phosphate anion is also in direct
      contact with the ribose moiety of formycin B. The ribose binding site is composed
      of Ser90, Met180, Glu181 and His4, the latter belonging to the neighbouring
      subunit. The base binding site is exposed to solvent, and the base is
      unspecifically bound through a chain of water molecules and aromatic-aromatic
      interactions. In all monomers the nucleosides are in the high syn conformation
      about the glycosidic bonds with chi in the range 100 to 130 degrees. The
      architecture of the active centre is in line with the known broad specificity and
      the kinetic properties of E. coli PNP.

PMID- 9653039
TI  - Contribution of individual residues to formation of the native-like tertiary
      topology in the alpha-lactalbumin molten globule.
AB  - Molten globules are partially folded forms of proteins that have native-like
      secondary structure and a compact geometry, but often without rigid, specific
      side-chain packing. Recently, the molten globule of alpha-lactalbumin (alpha-LA)
      has been shown to adopt a native-like tertiary topology, mainly localized in the
      alpha-helical domain. This native-like topology is reflected by the high
      effective concentration (Ceff) for formation of the 28-111 disulfide bond, which
      is approximately 10 to 40 times higher than the Ceff for formation of any non
      native disulfide bond in the alpha-helical domain. In order to understand the
      mechanism for formation of the native-like tertiary topology, we substituted
      alanine for each of the 23 buried residues in the alpha-helical domain of alpha
      LA and determined the effect of these substitutions on the Ceff for formation of
      the 28-111 disulfide bond. Our results indicate that a subset of hydrophobic
      residues is most important for formation of the native-like topology. These
      residues form a densely packed core in the three-dimensional structure of alpha
      LA. In contrast, the less important residues consist of both hydrophobic and
      hydrophilic amino acids located at peripheral positions. These results suggest
      that a relatively small number of hydrophobic residues may be sufficient for
      specifying the overall structure of a protein during early stages of protein
      folding.

PMID- 9653041
TI  - Introduction.

PMID- 9653040
TI  - A specific hydrophobic core in the alpha-lactalbumin molten globule.
AB  - Molten globules are partially structured protein folding intermediates that adopt
      a native-like overall backbone topology in the absence of extensive detectable
      tertiary interactions. It is important to determine the extent of specific
      tertiary structure present in molten globules and to understand the role of
      specific side-chain packing in stabilizing and specifying molten-globule
      structure. Previous studies indicate that a small degree of specific side-chain
      packing stabilizes the structures of the cytochrome c, apomyoglobin, and
      staphylococcal nuclease molten globules. Here we investigate the extent of
      specific side-chain packing in the molten globule of alpha-lactalbumin (alpha
      LA), a highly fluctuating, non-cooperatively formed molten globule. By analyzing
      a set of point mutations in the helical domain of alpha-LA, we have identified a
      stabilizing hydrophobic core. Moreover, this core corresponds to a previously
      identified structural subdomain and likely contains some native-like packing
      interactions. Our results suggest that native-like packing of core amino acids
      helps stabilize molten globules and that some specific interactions can exist in
      even highly dynamic, fluctuating species.

PMID- 9653042
TI  - Introduction: HIV co-receptors solve old questions and raise many new ones.

PMID- 9653043
TI  - Microbial corruption of the chemokine system: an expanding paradigm.
AB  - The chemokine signaling system includes more than 40 secreted pro-inflammatory
      peptides and 12 G protein-coupled receptors that together orchestrate specific
      leukocyte trafficking in the mammalian immune system, ideally for anti- microbial
      defense and tissue repair processes. Paradoxically and perversely, some
      chemokines and chemokine receptors are also promicrobial factors and facilitate
      infectious disease, the result of either exploitation or subversion by specific
      microbes. Two modes of exploitation are known: usage of cellular chemokine
      receptors for cell entry by intracellular pathogens, including HIV, and usage of
      virally-encoded chemokine receptors for host cell proliferation. Likewise, two
      modes of subversion are known: virally-encoded chemokine antagonists and virally
      encoded chemokine scavengers. Understanding how microbes turn the tables on the
      chemokine system may point to new methods to prevent or treat infection, or, more
      generally, to treat inappropriate chemokine-mediated inflammation.

PMID- 9653044
TI  - A novel CXC chemokine PBSF/SDF-1 and its receptor CXCR4: their functions in
      development, hematopoiesis and HIV infection.
AB  - PBSF/SDF-1 is a CXC chemokine which has unique functions among chemokines. It is
      essential for viability of the embryo, B lymphopoiesis, bone marrow hematopoiesis
      and cardiogenesis. A receptor for PBSF/SDF-1 was shown to be CXCR4 that is an
      entry co-receptor for T cell line-tropic HIV-1. Although murine cells had been
      thought to have no functional co-receptors, murine CXCR4 allowed entry of HIV-1
      into target cells with human CD4. In addition, a small molecule CXCR4 inhibitor
      that blocks HIV-1 entry was identified.

PMID- 9653045
TI  - Chemokine receptor allelic polymorphisms: relationships to HIV resistance and
      disease progression.
AB  - It is now well established that an array of CC and CXC chemokine receptors, in
      association with the CD4 molecule, can interact with the HIV-1 gp120 protein to
      facilitate viral fusion. A 32bp deletion in the CC chemokine receptor CCR5, the
      major M-tropic viral co-receptor, provides considerable protection against HIV-1
      transmission and has been associated with a delay in disease progression. The
      effects of the Delta32 allele appear to be mediated through the phenotype of CCR5
      expression as opposed to genotype. Here we discuss the potential effects that the
      Delta32 allele and other polymorphisms in the chemokine receptor repertoire may
      have on both HIV-1 transmission and disease progression.

PMID- 9653046
TI  - The role of co-stimulation in regulation of chemokine receptor expression and HIV
      1 infection in primary T lymphocytes.
AB  - Fusion and entry of the human immunodeficiency virus (HIV) into CD4(+) T
      lymphocytes requires expression of CD4 and a coreceptor. At least eight chemokine
      receptors can serve as coreceptors for HIV. Accumulating evidence indicates that
      multiple factors, including the state of cellular differentia- tion and
      activation, regulate the expression of alpha- and beta-chemokine receptors on
      lymphocytes. For example, binding of antibodies to the CD28 coreceptor can
      downregulate expression of beta-chemokine receptors, and this appears to have
      important consequences on the susceptibility of CD4(+) T lymphocytes to infection
      by HIV-1. In contrast, binding of the natural CD28 ligand B7 or antibodies to the
      CD28 homologue CTLA-4 can upregulate CCR5 expression, sug- gesting a reciprocal
      interaction between CD28 and CTLA-4 and the regulation of beta-chemokine receptor
      expression. Thus, the CD28/CTLA-4/B7 co-stimulation pathway is identi- fied as a
      potential novel target for the control of susceptibility to some strains of HIV-1
      infection.

PMID- 9653047
TI  - Chemokine receptors in HIV-1 infection of the central nervous system.
AB  - Several members of the chemokine receptor are used as coreceptors for HIV-1
      infection in the central nervous system (CNS). CCR5 and CCR3 are coreceptors
      together with CD4 for HIV-1 infection of microglia, the major target for HIV-1
      infection in the CNS. Microglia express CXCR4, but their infection by HIV-1
      viruses that use only CXCR4 as a coreceptor is relatively inefficient. CXCR4 is
      also expressed in subpopulations of neurons that are resistant to HIV-1
      infection. Additional orphan chemokine receptors that can mediate HIV-1 or SIV
      entry are expressed in the brain or neurally-derived cell lines, but their role
      in CNS infection has not been defined. The pattern of chemokine receptor
      expression in the brain is likely to determine the tropism of HIV-1 for
      particular CNS target cells and to impact inflammatory and degenerative
      mechanisms associated with CNS infection.

PMID- 9653048
TI  - The function of simian chemokine receptors in the replication of SIV.
AB  - The long sought co-receptors for primate lentiviruses were identified as
      belonging to a large family of cell surface proteins - the seven transmembrane
      proteins. These proteins normally function as cell surface receptors for
      chemokines and other ligands. The families of genetically divergent Simian
      Immunodeficiency Viruses (SIV), which include the origins of HIV-1 and HIV-2, use
      simian and human chemokine receptors as their co-receptors. SIVmac, SIVsm, SIVagm
      and SIVcpz use monkey and human CCR5 for cell fusion and entry. Human-derived
      STRL33 (BONZO) and human-derived GPR-15 (BOB) are also used, but with variable
      efficiency. True primary strains of SIVsm, obtained from the naturally infected
      simian host, the sooty mangabey, use simian and human CCR5 in a strongly CD4
      dependent manner. However, some brain and lymphoid isolates from the experimental
      simian host, the macaque use CCR5 independently of CD4. Unlike T cell line
      adapted (TCLA) CXCR4-tropic HIV strains (XR4 HIV), only a few laboratory SIV
      strains use CXCR4 for entry. Macaque and mangabey CXCR4 are fully functional,
      because they are highly efficient for entry of XR4 HIV. The CCR5 co-receptor is
      used by three of four SIV families tested thus far. The fourth family,
      represented by the isolate, S1Vrcm95GB1, is unique among SIV and HIV in its use
      of CCR2b but not CCR5.

PMID- 9653049
TI  - G protein-coupled receptors in HIV and SIV entry: new perspectives on lentivirus
      host interactions and on the utility of animal models.
AB  - Entry of primate lentiviruses into target cells has recently been shown to depend
      upon the interaction of the viral envelope glycoprotein with CD4 and one or more
      members of the G protein-coupled receptor (GPCR) family of transmembrane
      proteins. In vivo, the transmission of HIV-1 infection generally requires viral
      strains that utilise chemokine recep- tor CCR5, and these strains prevail during
      the early course of infection. Strains isolated later, in the course of
      progression to immunodeficiency, are often CXCR4-tropic or are dual tropic for
      both chemokine receptors. SIV isolates also use CCR5 but are only rarely specific
      for CXCR4. Instead, SIVs use two orphan members of the GPCR family, named
      Bonzo/STRL33/TYMSTR and BOB/GPR15. Strains of HIV-2, which are closely related to
      the SIVs, also often utilise CXCR4, CCR5, BOB and/or Bonzo. Additional GPCR
      family members have also been shown to be utilised by various strains of HIV and
      SIV, albeit less efficiently and less frequently. Here we discuss the potential
      relationship between receptor specificity and viral pathogenesis as well as
      efforts to develop animal model systems to study the mechanism of disease
      progression.

PMID- 9653050
TI  - Structure-function studies of the HIV-1 coreceptors.
AB  - Ten seven-transmembrane-domain G protein-coupled receptors have been identified
      that are functional HIV-1, HIV-2 and SIV coreceptors. However, the specific
      structures these receptors have in common that enable them to mediate HIV entry
      are unknown. Structure-function analyses have revealed that the determinants of
      coreceptor activity are distinct for each coreceptor, coreceptor activity is
      dependent on multiple extracellular domains, and various envelope proteins may
      interact differently with the same coreceptor. G protein coupling and receptor
      internalization are not required for fusion and infection of established cell
      lines, or for inhibition of infection by chemokines. The structure-function
      studies have also helped determine the mechanism by which previously described
      small molecules inhibit HIV-1 entry. Finally, these studies have led to a
      hypothesis as to how coreceptor utilization evolves during the course of an
      infection.

PMID- 9653051
TI  - Structural interactions between chemokine receptors, gp120 Env and CD4.
AB  - Seven transmembrane segment (7TMS) receptors for chemokines and related molecules
      have been demonstrated to be essential, in addition to CD4, for HIV and SIV
      infection. The beta-chemokine receptor CCR5 is the primary, perhaps sole, co
      receptor for HIV-1 during the early and chronic phases of infection and supports
      infection by most primary HIV-1 and many SIV isolates. Late-stage primary and
      laboratory-adapted HIV-1, HIV-2, and SIV isolates can use other 7TMS receptors.
      CXCR4 appears especially important in late-stage HIV infection; several related
      receptors can also be used. The specificity of SIV viruses is similar.
      Commonalities among these receptors, combined with analyses of mutated molecules,
      indicate that discrete, conformationally-dependent sites on the chemokine
      receptors determine their association with the third variable and conserved
      regions of viral envelope glycoproteins. These studies are useful for elucidating
      the mechanism and molecular determinants of HIV-1 entry, and of inhibitors to
      that entry.

PMID- 9653052
TI  - A physiologically based pharmacokinetic description of the oral uptake, tissue
      dosimetry, and rates of metabolism of bromodichloromethane in the male rat.
AB  - Bromodichloromethane (BDCM), a trihalomethane (THM) and water chlorination by
      product, induces cancer in several tissues in experimental animals, including
      target tissue sites where increased incidences of human cancer have been linked
      to consumption of chlorinated water. The purpose of the present study was to
      examine the effects of vehicle of administration on the pharmacokinetics of
      orally administered BDCM and to further develop and validate a physiologically
      based pharmacokinetic (PBPK) model to describe BDCM absorption, tissue dosimetry,
      and rates of metabolism for both oil and 10% Emulphor vehicles. Estimates of oral
      absorption rate constants were determined by fitting blood and exhaled breath
      chamber concentration-time curves obtained following gavage of male F344 rats
      with 50 or 100 mg BDCM/kg in corn oil or 10% Emulphor using a previously
      published multicompartmental gastrointestinal tract submodel (Semino et al.,
      Toxicology 117, 25-33, 1997) linked to a PBPK model. Independently estimated oral
      uptake and metabolic rate constants accurately described kidney BDCM
      concentrations and plasma bromide ion levels without adjustment. This observation
      increases our confidence in model structure and values of parameter estimates.
      Liver BDCM concentrations were simulated, but with less accuracy than kidney
      dosimetry simulations, following incorporation of BDCM loss to metabolism during
      sample preparation. This model describes BDCM tissue dosimetry and metabolism
      following oral gavage and can be utilized in estimating rates of formation of
      reactive metabolites in target tissues. Estimates of tissue dosimetry and levels
      of toxic intermediates can be incorporated into a risk assessment model for BDCM
      induced toxicity and carcinogenicity.

PMID- 9653053
TI  - The role of IgG1 and IgG2 in trimellitic anhydride-induced allergic response in
      the guinea pig lung.
AB  - Trimellitic anhydride (TMA) is a small molecular weight chemical used in the
      paint and plastics industry that can cause asthma-like symptoms in humans. Guinea
      pigs sensitized intradermally with TMA will respond to antigen challenge with
      asthma-like symptoms, including an immediate bronchoconstriction and a delayed
      cellular infiltration into the lung, particularly eosinophil infiltration.
      Sensitized guinea pigs produce TMA-specific IgG1, which is thought to be
      important in asthmatic reactions in this animal model; however, they also produce
      TMA-specific IgG2 antibody. The purpose of the present study was to determine the
      role of IgG1 and IgG2 in the TMA-induced immediate bronchoconstriction and
      delayed cellular infiltration in the guinea pig. Guinea pigs were passively
      sensitized by intratracheal instillation of TMA-specific IgG2, an antibody
      preparation enriched with TMA-specific IgG1, or a combination of the two. The
      allergic response was induced by intratracheal instillation of TMA conjugated to
      guinea pig serum albumin (TMA-GPSA). A significantly greater bronchoconstrictor
      response was observed in animals sensitized with a combination of the IgG2 and
      IgG1 preparation compared to those sensitized with IgG2 or the IgG1 preparation
      alone. Cellular infiltration was quantified 24 h after antigen challenge by
      differential cell counts of bronchoalveolar lavage (BAL) cells as well as by
      using eosinophil peroxidase (EPO) and myeloperoxidase (MPO) activity as a measure
      of the numbers of eosinophils and neutrophils, respectively. In the BAL,
      passively sensitizing with IgG2 alone resulted in an increase in both TMA-induced
      MPO and EPO activity. In contrast, in the lung, passively sensitizing with a
      partially purified preparation of TMA-specific IgG1 alone resulted in a
      significant increase in TMA-induced EPO activity. Passively sensitizing with IgG2
      in conjunction with the IgG1 preparation resulted in an enhanced cellular
      infiltration and lung injury over that seen with either antibody preparation
      alone. These data demonstrate an augmentation of IgG1-mediated responses by the
      addition of IgG2 and suggest a significant role for both subclasses of IgG
      antibodies in this guinea pig model of TMA-induced occupational asthma.

PMID- 9653054
TI  - Responsiveness of the adult male rat reproductive tract to 2,3,7,8
      tetrachlorodibenzo-p-dioxin exposure: Ah receptor and ARNT expression, CYP1A1
      induction, and Ah receptor down-regulation.
AB  - Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) either in adulthood or
      during late fetal and early postnatal development causes a variety of adverse
      effects on the male rat reproductive system. It was therefore of interest to
      identify male rat reproductive organs and cell types within these organs that
      might be direct targets of TCDD exposure. Because TCDD toxicity could possibly be
      the result of alterations in gene transcription mediated by the TCDD/aryl
      hydrocarbon receptor (AhR)/AhR nuclear translocator (ARNT) complex, the presence
      of the AhR and ARNT in the various organs of the adult male reproductive tract
      was examined using Western blotting. Both proteins were detectable in all organs
      examined (testis, epididymis, vas deferens, ventral prostate, dorsolateral
      [combined dorsal and lateral] prostate, and seminal vesicle). Although technical
      difficulties precluded the immunohistochemical evaluation of AhR distribution in
      these organs, ARNT was localized in all organs in a variety of cell types,
      including germ cells, epithelial cells, fibroblasts, smooth muscle cells, and
      endothelial cells. Subcellular localization varied across organs and across cell
      types within these organs. In order to determine whether TCDD exposure could
      alter gene expression in these organs, animals were dosed with TCDD (25
      micrograms/kg po) or vehicle and euthanized at 24 h, and cytochrome P4501A1
      (CYP1A1) expression was evaluated. By Western blotting, only the ventral and
      dorsolateral prostates exhibited significant induction of CYP1A1.
      Immunohistochemistry confirmed this induction and localized CYP1A1 expression to
      epithelial cells of the ventral and lateral lobes of the prostate.
      Immunohistochemistry also revealed CYP1A1 induction in select epithelial cells in
      the epididymis and seminal vesicle, as well as endothelial cells in the vas
      deferens and seminal vesicle. No induction was observed in the testis. Finally,
      AhR and ARNT expression in TCDD-exposed and control animals was evaluated by
      Western blotting. Results revealed no effect of TCDD exposure on ARNT protein
      expression, while AhR expression was decreased to 5-51% of control in all organs
      examined. In summary, both AhR and ARNT were expressed in all organs of the adult
      male rat reproductive tract examined, and epithelial and/or endothelial cells
      within each of these organs (with the exception of the testis) were responsive to
      TCDD exposure in terms of CYP1A1 induction. In addition, all tissues exhibited
      marked reductions in AhR protein content after TCDD exposure that did not
      correlate with the magnitude of the CYP1A1 response.

PMID- 9653055
TI  - In utero and lactational exposure of the male rat to 2,3,7,8-tetrachlorodibenzo-p
      dioxin impairs prostate development. 1. Effects on gene expression.
AB  - In utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure
      decreases rat prostate weight without decreasing circulating androgen
      concentrations. Because one mechanism by which TCDD is thought to cause toxicity
      is by aryl hydrocarbon receptor (AhR)-mediated alterations in gene transcription,
      the goals of this study were to determine whether the developing prostate
      expresses the AhR and its dimerization partner, the AhR nuclear translocator
      (ARNT); to determine whether in utero and lactational TCDD exposure is capable of
      directly activating gene transcription in the developing prostate; and to
      identify prostatic mRNAs that exhibit altered abundance in response to in utero
      and lactational TCDD exposure. Pregnant Holtzman rats were administered TCDD (1.0
      microgram/kg po) or vehicle on Gestation Day (GD) 15, and male offspring were
      euthanized between Postnatal Days (PNDs) 1 and 63. Using reverse transcriptase
      polymerase chain reaction (RT-PCR), mRNAs encoding the AhR and ARNT were detected
      in both ventral and dorsolateral prostates from control animals throughout
      postnatal development. ARNT protein was expressed in the majority of stromal
      nuclei early in development, whereas ARNT expression in the prostate epithelium
      was initially cytoplasmic but became nuclear as development progressed. GD 15
      TCDD exposure increased cytochrome P4501A1 (CYP1A1) mRNA and protein in whole
      prostates between PNDs 7 and 21. In these TCDD-exposed animals, CYP1A1 protein
      was localized to the epithelium. In order to define other genes in the developing
      prostate that might be regulated by TCDD at the level of mRNA, RNA samples from
      PND 21 whole prostates from control and TCDD-exposed animals were compared using
      mRNA differential display. Although no growth-regulatory candidates were
      identified using this screening technique, a ventral prostate-specific, androgen
      regulated mRNA (20-kDa protein) was identified that seemed to be downregulated by
      TCDD exposure. Northern blot analysis confirmed this decrease at PND 21 and
      further showed that the downregulation was transient. Similar results were
      obtained for four additional androgen-regulated prostatic mRNAs (prostatic
      binding protein [PBP], Royal Winnipeg Ballet [RWB], probasin, and dorsal protein
      1 [DP-1]), all of which are markers of a differentiated ductal epithelium. In
      contrast, TCDD exposure of adult male rats (25 micrograms TCDD/kg, 24 h) greatly
      induced CYP1A1 mRNA without affecting the abundance of prostate-specific,
      androgen-regulated mRNAs. These results suggest that the transient decreases in
      androgen-regulated prostatic mRNA abundance observed in response to in utero and
      lactational TCDD exposure were probably not the result of direct action of the
      activated AhR on these genes but instead were reflective of a TCDD-induced delay
      in prostate development.

PMID- 9653056
TI  - In utero and lactational exposure of the male rat to 2,3,7,8-tetrachlorodibenzo-p
      dioxin impairs prostate development. 2. Effects on growth and
      cytodifferentiation.
AB  - In the male Holtzman rat, in utero and lactational 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) exposure decreases prostate weight without inhibiting testicular
      androgen production or decreasing circulating androgen concentrations. Therefore,
      the present study sought to characterize effects of TCDD exposure on prostate
      development, from very early outgrowth from the urogenital sinus (Gestation Day
      [GD] 20) until rapid growth and differentiation are essentially complete
      (Postnatal Day [PND] 32). Pregnant Holtzman rats were administered a single dose
      of TCDD (1.0 microgram/kg po) or vehicle on GD 15 and offspring were exposed via
      placental transfer (GD 20 euthanasia) or placental and subsequent lactational
      transfer until euthanasia (if before PND 21) or weaning. Results show that the
      prostatic epithelial budding process was impaired by in utero TCDD exposure, as
      evidence by significant decreases in the number of buds emerging from dorsal,
      lateral, and ventral aspects of the GD 20 urogenital sinus. Ventral prostate cell
      proliferation index was significantly decreased on PND 1 but was similar to or
      higher than control at later times, whereas apoptosis was an extremely rare event
      in ventral prostates from both control and TCDD-exposed animals. Delays were
      noted in the differentiation of pericordal smooth muscle cells and luminal
      epithelial cells. In addition, ventral prostates from approximately 40% of TCDD
      exposed animals examined on PNDs 21 and 32 exhibited alterations in the
      histological arrangement of cell types that could not be explained by a
      developmental delay. Compared to controls, these ventral prostates exhibited a
      disorganized, hyperplastic epithelium containing fewer luminal epithelial cells
      and an increased density or continuous layer of basal epithelial cells, as well
      as thicker periductal smooth muscle sheaths. In addition, in ventral prostates
      from TCDD-exposed animals, the intensity of androgen receptor staining was
      relatively low in the central and distal epithelium, and the number of androgen
      receptor-positive cells was relatively high in the periductal stroma. These data
      suggest that in utero and lactational TCDD exposure interferes with prostate
      development by decreasing very early epithelial growth, delaying
      cytodifferentiation, and, in the most severely affected animals, producing
      alterations in epithelial and stromal cell histological arrangement and the
      spatial distribution of androgen receptor expression that may be of permanent
      consequence.

PMID- 9653057
TI  - Glia increase degeneration of hippocampal neurons through release of tumor
      necrosis factor-alpha.
AB  - This study characterizes the role of glial cells in chemically induced
      neurodegeneration. We evaluated the effect of trimethyltin, a trisubstituted
      organotin compound that elicits distinct lesions in the central nervous system in
      vivo, on a sandwich co-culture of neurons and glia. Exposure of a 98% pure
      culture of rat hippocampal neurons to 0.1-1 microM trimethyltin for 24 h caused
      neural cell death and nuclear changes typical of apoptosis; at these doses glial
      cells viability was not affected but the cells released significant amounts of
      tumor necrosis factor-alpha (TNF-alpha). Neuronal apoptosis and TNF-alpha release
      from glial cells both increased when the two cell types were exposed together to
      trimethyltin, which indicates synergy. Treatment of a neuron-glia co-culture with
      TNF-alpha antibody prevented the increase in neuronal apoptosis, and TNF-alpha
      administration induced apoptosis in hippocampal cells. We conclude that glial
      cells and TNF-alpha both modulate trimethyltin-induced neurodegeneration.

PMID- 9653059
TI  - Dichloroacetate and trichloroacetate promote clonal expansion of anchorage
      independent hepatocytes in vivo and in vitro.
AB  - Dichloroacetate (DCA) and trichloroacetate (TCA) are hepatocarcinogenic by
      products of water chlorination and metabolites of several industrial solvents. To
      determine whether DCA and TCA promote the clonal expansion of anchorage
      independent liver cells in vitro, a modification of the soft agar assay (over
      agar assay) was utilized to quantitate growth and analyze phenotype of anchorage
      independent hepatocellular colonies. Hepatocytes from naive male B6C3F1 mice were
      isolated and cultured with 0-2.0 mM DCA or TCA over agar for 10 days, at which
      time colonies of eight cells or more were scored. Both DCA and TCA promoted the
      formation of anchorage-independent colonies in a dose-dependent manner.
      Immunocytochemical analysis using a c-Jun antibody demonstrated that colonies
      promoted by DCA were primarily c-Jun+, whereas TCA-promoted colonies were
      primarily c-Jun-. This corresponds to the differences in c-Jun immunoreactivity
      reported in tumors induced by DCA and TCA. Neither DCA nor TCA induced c-Jun
      expression in hepatocyte monolayers, indicating that these haloacetates
      selectively affect subpopulations of anchorage-independent hepatocyts. The
      latency of colony formation was decreased by the concentration of DCA, although
      the same number of colonies appeared after 25 days in culture at all DCA
      concentrations used. The plating density of hepatocytes also affected colony
      formation. At lower cell densities, promotion of colony formation by DCA was
      significantly reduced. Pretreatment of male B6C3F1 mice with 0.5 g/liter DCA in
      drinking water resulted in a fourfold increase in in vitro colony formation above
      hepatocytes isolated from naive mice, suggesting that DCA is promoting the clonal
      expansion of anchorage-independent hepatocytes in vivo. Results from this study
      indicate that DCA and TCA promote the survival and growth of initiated cells.
      Furthermore, results from over agar assays reflect observations made in vivo,
      indicating this assay provides a valid means to investigate the mechanism by
      which chemicals promote clonal expansion of initiated hepatocytes.

PMID- 9653058
TI  - Effect of rodent hepatocarcinogenic peroxisome proliferators on fatty acyl-CoA
      oxidase, DNA synthesis, and apoptosis in cultured human and rat hepatocytes.
AB  - The effects of the rodent hepatocarcinogens clofibric acid and diprofibrate on
      the activity of the peroxisomal fatty acyl-CoA oxidase, DNA synthesis, and
      apoptosis were compared in cultured rat and human hepatocytes. Rat hepatocytes
      expressed a 10-fold greater level of the peroxisomal fatty acyl-CoA oxidase
      compared to human hepatocytes. At the highest concentration (1.0 mM), both drugs
      induced a two- to threefold increase in this enzyme activity in both rat and
      human hepatocytes. Ciprofibrate (0.1 and 0.2 mM) caused a twofold increase in DNA
      synthesis in rat hepatocytes, whereas clofibric acid had no effect on DNA
      synthesis in these cells. In contrast, increasing concentrations of both
      clofibric acid and ciprofibrate produced inhibition of DNA synthesis in human
      hepatocytes. By using the terminal transferase dUTP-biotin nick end labeling
      technique, it was observed that 0.1 and 0.2 mM clofibric acid and ciprofibrate
      suppressed transforming growth factor-beta (TGF beta)-induced apoptosis by 50% in
      rat hepatocytes, but they had no effect on TGF beta-induced apoptosis in human
      hepatocytes. Although clofibric acid and ciprofibrate diminished TGF beta-induced
      apoptosis, they had no effect on the basal apoptotic levels in the rat hepatocyte
      cultures. However, both drugs significantly increased the percent of apoptotic
      cells in the human hepatocyte cultures. It is concluded that primary rat and
      human hepatocyte cultures respond differently to peroxisome proliferators. The
      differences in effects on DNA synthesis and apoptosis support the hypothesis that
      human liver cells are refractory to peroxisome proliferator-induced
      hepatocarcinogenesis.

PMID- 9653060
TI  - Interspecies scaling of clearance and volume of distribution for horse antivenom
      F(ab')2.
AB  - F(ab')2 fragments are sometimes preferred to whole IgG for therapeutic or
      diagnostic uses. Preclinical pharmaceutical development studies are necessary
      before their use in humans. Here we propose an allometric approach among three
      mammalian species to predict F(ab')2 pharmacokinetic parameters in humans. Plasma
      disposition of horse antivenom F(ab')2 fragments labeled with iodine 125 was
      studied at a dose of 10 mg/kg i.v. in mice, rats, and rabbits. Using the
      allometric method, we demonstrate that the pharmacokinetic parameters that
      correlated with body weight were distribution volume (Vdc (ml) = 0.125 W0.87;
      Vdss (ml) = 0.251 W0.87; Vd beta (ml) = 0.290 W0.87, r2 = 1), total clearance
      (Cltot (ml/h) = 0.049 W0.53, r2 = 0.99), and terminal half-life (t1/2 beta (h) =
      4.35 W0.33). The F(ab')2 plasma concentration-time data plotted as a complex
      Dedrick relationship were superimposable. Using these allometric techniques,
      Vdss, Vd beta, Cltot, and t1/2 beta were calculated as 4.12 liter, 4.78 liter,
      19.07 ml/h, and 7.2 days, respectively, for a human subject of 70 kg body wt.
      Predicted human pharmacokinetic parameters were comparable for volume of
      distribution with the value reported by Hnatowich et al. (Cancer Res. 47, 6111
      6117, 1987): 3.5 liter. However, the clearance was six-fold lower than values
      given by Hnatowich et al. (130 ml/h) and Ho et al.

PMID- 9653061
TI  - Role of oxidative stress in the selective toxicity of dieldrin in the mouse
      liver.
AB  - Dieldrin, an organochlorine insecticide, induces hepatic tumors in mice but not
      in rats. Although the mechanism(s) responsible for this species specificity is
      not fully understood, accumulating evidence indicates that oxidative stress may
      be involved. This study examined the association of dieldrin-induced hepatic DNA
      synthesis with the modulation of biomarkers of oxidative damage to lipids
      (malondialdehyde [MDA]) and DNA (8-hydroxy-2-deoxyguanosine [oh8dG]), in male
      B6C3F1 mice and F344 rats fed dieldrin (0.1, 1.0, or 10 mg/kg diet) for 7, 14,
      28, and 90 days. The nonenzymatic components of the antioxidant defense system
      (ascorbic acid, glutathione, and alpha-tocopherol) were also examined. Increased
      urinary MDA was observed in mice fed 0.1, 1.0, or 10 mg dieldrin/kg diet for 7,
      14, 28, and 90 days; while increased hepatic MDA was seen only after 7 days in
      mice fed 0.1, 1.0, or 10 mg dieldrin/kg diet and after 14 days in mice fed 10
      mg/kg diet. In rats, dieldrin had no effect on either hepatic MDA or urine MDA
      levels after 7, 14, and 28 days of treatment. A dose-dependent increase in
      urinary MDA was observed in rats at the 90-day sampling time. The only
      significant elevation in urinary or hepatic oh8dG content was limited to urinary
      oh8dG in mice fed 10 mg/kg dieldrin diet for 14 days. Dietary dieldrin produced
      sustained decreases in hepatic and serum alpha-tocopherol and sustained
      elevations in hepatic ascorbic acid in both mice and rats. Rats, however,
      possessed a three- to four-fold higher content of endogenous or basal (control)
      hepatic alpha-tocopherol; and, even when fed 10 mg dieldrin/kg diet, the levels
      of hepatic alpha-tocopherol were maintained at higher levels than those of mice
      fed control diet. In both rats and mice fed dieldrin, transient (14 and 28 days
      on diet) elevations in hepatic glutathione were observed. These data support the
      hypothesis that the species specificity of dieldrin-induced hepatotoxicity may be
      related to dieldrin's ability to induce oxidative stress in the liver of mice,
      but not in rats. Only in mice fed dieldrin was a temporal association of
      increases in hepatic MDA content and hepatic DNA synthesis seen, suggesting that
      oxidative damage (shown by increased lipid peroxidation) may be involved in early
      events in dieldrin-induced hepatocarcinogenesis. Rats may be protected from
      dieldrin-induced oxidative stress by a more effective antioxidant defense system,
      characterized by higher basal levels of hepatic alpha-tocopherol and ascorbic
      acid than that seen in the mouse.

PMID- 9653062
TI  - Detection of the sarin hydrolysis product in formalin-fixed brain tissues of
      victims of the Tokyo subway terrorist attack.
AB  - One of the hydrolysis products of sarin (isopropyl methylphosphonofluoridate) was
      detected in formalin-fixed brain tissues of victims poisoned in the Tokyo subway
      terrorist attack. Part of this procedure, used for the detection of sarin
      hydrolysis products in erythrocytes of sarin victims, has been described
      previously. The test materials were four individual cerebellums, which had been
      stored in formalin fixative for about 2 years. Sarin-bound acetylcholinesterase
      (AChE) was solubilized from these cerebellums, purified by immunoaffinity
      chromatography, and digested with trypsin. Then the sarin hydrolysis products
      bound to AChE were released by alkaline phosphatase digestion, subjected to
      trimethylsilyl derivatization (TMS), and detected by gas chromatography-mass
      spectrometry. Peaks at m/z 225 and m/z 240, which are indicative of TMS
      methylphosphonic acid, were observed within the retention time range of authentic
      methylphosphonic acid. However, no isopropyl methylphosphonic acid was detected
      in the formalin-fixed cerebellums of these 4 sarin victims, probably because the
      isopropoxy group of isopropyl methylphosphonic acid underwent chemical hydrolysis
      during storage. This procedure will be useful for the forensic diagnosis of
      poisoning by protein-bound, highly toxic agents, such as sarin, which are easily
      hydrolysed. This appears to be the first time that intoxication by a nerve agent
      has been demonstrated by analyzing formalin-fixed brains obtained at autopsy.

PMID- 9653063
TI  - Pharmacological profile of CEB-1957 and atropine toward brain muscarinic
      receptors and comparative study of their efficacy against sarin poisoning.
AB  - This study consists of two parts, first to compare the pharmacological profile of
      atropine and CEB-1957 substance toward muscarinic receptor subtypes. In various
      rat brain structures, binding properties were determined by competition
      experiments of [3H]pirenzepine, [3H]AF-DX 384, and [3H]4-DAMP in quantitative
      autoradiography of M1, M2, and M3 muscarinic receptor subtypes, respectively.
      Competition curves have shown that atropine presents similar nanomolar inhibition
      constants toward each subtype, while CEB-1957 has distinct affinities (Ki from
      0.26 to 73 nM) with the following range order: M3 > or = M2 > M1. The second part
      is to compare atropine and CEB-1957 (in combination with pralidoxime) for their
      ability to protect against the lethality induced by 2 x LD50 of the
      acetylcholinesterase inhibitor sarin. CEB-1957 reduced the mortality at doses 10
      times lower than atropine. Finally, from these results, it is proposed that a
      selective blockade of M2 and M3 receptor subtypes could play a pivotal role in
      the protective effect against sarin poisoning.

PMID- 9653064
TI  - Inhalation of diesel exhaust enhances allergen-related eosinophil recruitment and
      airway hyperresponsiveness in mice.
AB  - We have previously shown that intratracheal instillation of suspension of diesel
      exhaust particles enhances allergen-related eosinophilic airway inflammation,
      airway hyperresponsiveness, and local expression of interleukin (IL)-5 and
      granulocyte macrophage-colony stimulating factor (GM-CSF) in mice. The present
      study was designed to elucidate the effects of daily inhalation of diesel exhaust
      (DE) on the allergen-related respiratory disease. ICR mice were exposed for 40
      weeks to clean air or DE at a soot concentration of 0.3, 1.0, or 3.0 mg/m3 with
      aerosol allergen challenges (1% ovalbumin in isotonic saline for 6 min) at 3-week
      intervals during the last 24 weeks of exposures. Exposure to DE enhanced allergen
      related eosinophil recruitment to the submucosal layers of the airways and to the
      bronchoalveolar space, and increased protein levels of GM-CSF and IL-5 in the
      lung in a dose-dependent manner compared to exposure to clean air. There were
      strong correlations between the number of eosinophils in bronchoalveolar lavage
      (BAL) fluid and IL-5 concentrations in BAL supernatants and lung tissue
      supernatants. In addition, the increases in eosinophil recruitment and local
      cytokine expression were accompanied by goblet cell proliferation in the
      bronchial epithelium and airway hyperresponsiveness to inhaled acetylcholine. In
      contrast, the control mice exposed for 40 weeks to clean air or DE at a soot
      concentration of 0.3, 1.0, or 3.0 mg/m3 without allergen provocation showed no
      eosinophil recruitment to the submucosal layers of the airways nor to the
      bronchoalveolar space and few goblet cells in the bronchial epithelium. The
      present study provides experimental evidence that daily inhalation of DE can
      enhance allergen-related respiratory diseases such as allergic asthma. This
      effect may be mediated by the enhanced local expression of IL-5 and GM-CSF.
      Increased ambient levels of DE may be implicated in the increasing prevalence of
      bronchial asthma in recent years.

PMID- 9653066
TI  - A comparison of the electrophysiological effects of two organophosphates, mipafox
      and ecothiopate, on mouse limb muscles.
AB  - Adult male albino mice were given single subcutaneous injections of either
      mipafox (110 mumol/kg) or ecothiopate (0.5 mumol/kg), two organophosphorus
      compounds (OPs). Acetylcholinesterase activity was measured in the soleus (slow
      twitch) and extensor digitorum longus (EDL; fast-twitch) muscles. At 7 and 28
      days after dosing, in vitro electrophysiological measurements were carried out in
      the soleus and EDL. Action potentials and end-plate potentials were evoked at 30
      Hz and recorded intracellularly from single muscle fibers. The amplitudes, time
      course, and latencies of these potentials were measured and the variability
      (jitter) of latencies was calculated. Recordings after mipafox were also made
      with 3-Hz stimulation. Acetylcholinesterase activity was inhibited by mipafox
      (65% in the soleus; 76% in the EDL) and ecothiopate (59% in the soleus; 42% in
      the EDL). Mipafox and ecothiopate both increased postjunctional (muscle action
      potential) jitter in the soleus and EDL at 7 days after dosing. Organophosphates
      caused an increase in end-plate potential amplitudes in the soleus. Mipafox
      caused an increase in prejunctional (end-plate potential) jitter at 28 days after
      dosing in both muscles. A single dose of ecothiopate also caused an increase in
      prejunctional jitter at 28 days in the soleus. The OP-induced increase in jitter
      was different at different frequencies of stimulation. The results show that
      there are electrophysiological changes in both muscles after administration of
      organophosphorus compounds. The slow-twitch soleus appears more sensitive to
      prejunctional changes caused by OPs than the fast-twitch EDL.

PMID- 9653065
TI  - Lipid ozonation products activate phospholipases A2, C, and D.
AB  - Ozone exposure, in vitro, has been shown to activate phospholipases A2 (PLA2), C
      (PLC), and D (PLD) in airway epithelial cells. However, because of its high
      reactivity, ozone cannot penetrate far into the air/lung tissue interface. It has
      been proposed that ozone reacts with unsaturated fatty acids (UFA) in the
      epithelial lining fluid (ELF) and cell membranes to generate a cascade of lipid
      ozonation products (LOP) that mediate ozone-induced toxicity. To test this
      hypothesis, we exposed cultured human bronchial epithelial cells (BEAS-2B) to LOP
      (1-100 microM) produced from the ozonation of 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphatidylcholine (POPC) and measured the activity of PLA2, PLC, and PLD. The
      PLA2 isoform responsible for arachidonic acid release (AA) in stimulated cultures
      was also characterized. Activation of PLA2, PLC, and PLD by three oxidants,
      hydrogen peroxide (H2O2), tert-butyl hydroperoxide (t-BOOH) and 2,2'-azobis(2
      amidinopropane)dihydrochloride (AAPH) also was measured and compared to that of
      LOP. The derivatives of ozonized POPC at the sn-2 residue, 9-oxononanoyl (PC
      ALD), 9-hydroxy-9-hydroperoxynonanoyl (PC-HHP), and 8-(-5-octyl-1,2,4-trioxolan-3
      yl-) octanoyl (POPC-OZ) selectively activated PLA2 in a dose-dependent fashion.
      Cytosolic PLA2 (cPLA2) measured in the cytosolic fraction of stimulated cell
      lysates was found to be the predominant isoform responsible for AA release. PLC
      activation was exclusively induced by the hydroxyhydroperoxide derivatives. PC
      HHP and the 9-carbon hydroxyhydroperoxide (HHP-C9) increased PLC activity. PLD
      activity also was induced by LOP generated from POPC. Incubation of cultures with
      H2O2 alone did not stimulate PLC; however, in the presence of the aldehyde,
      nonanal, a 62 +/- 2% increase in PLC activity was found, suggesting that the
      increase in activity was due to the formation of the intermediate HHP-C9. t-BOOH,
      and AAPH also failed to induce PLA2 activation, but did activate PLC, under
      conditions of exposure identical to that of LOP. Only t-BOOH activated PLD. These
      results suggest that biologically relevant concentrations of LOP activate PLA2,
      PLC, and PLD in the airway epithelial cell, a primary target to ozone exposure.
      The activation of these phospholipases may play a role in the development of lung
      inflammation during ozone exposure.

PMID- 9653067
TI  - Methanol-induced contraction of canine cerebral artery and its possible mechanism
      of action.
AB  - In the present report, we investigated the effects of methanol on canine basilar
      cerebral arterial rings. Our data indicate that acute methanol exposure (5-675
      mM) induces potent contractile responses of cerebral arteries in a concentration
      dependent manner. Pharmacological antagonists, such as propranolol, phentolamine,
      haloperidol, methysergide, naloxone, diphenhydramine, and cimetidine, did not
      exert any effects on these methanol-induced contractions. Likewise, a potent
      antagonist of cyclo-oxygenase, and subsequent synthesis of prostanoids (i.e.,
      indomethacin), failed to exert any effect on methanol-induced contractions. No
      differences in responsiveness to methanol in canine cerebral arteries were found
      in vessel segments with or without endothelial cells. Removal of extracellular
      Ca2+ ([Ca2+]o) partially attenuated methanol-induced contractions, while
      withdrawal of extracellular Mg2+ ([Mg2+]o) potentiated the contractions. In the
      complete absence of [Ca2+]o, 10 mM caffeine and 400 mM methanol induced similar,
      transient contractions followed by relaxation in K(+)-depolarized cerebral
      vascular tissues. Methanol-induced contractions were, however, completely
      abolished by pretreatment of tissue with 10 mM caffeine. Our results indicate
      that (1) methanol causes contractile responses of cerebral arterial smooth muscle
      (independent of amine, prostanoid, or opioid mediation; (2) in addition to a need
      for [Ca2+]o, an intracellular release of Ca2+ is required for methanol-induced
      contractions; and (3) Mg deficiency potentiates the contractile responses of
      methanol on these brain vessels. The data presented in the study suggest that
      methanol-induced contractions occur via an sarcoplasmic reticulum-releasable
      store of [Ca2+]i; via mediation of either ryanodine-caffeine type receptors or a
      caffeine-releasable intracellular store of CA2+.

PMID- 9653068
TI  - Ortho-substituted polychlorinated biphenyls activate respiratory burst measured
      as luminol-amplified chemoluminescence in human granulocytes.
AB  - The effect of polychlorinated biphenyls (PCBs) on the activation of respiratory
      burst measured as luminol-amplified chemoluminescence in human granulocytes is
      elucidated here. Chemoluminescence was stimulated in a concentration-dependent
      manner (ED50 approximately 10 microM) by ortho-substituted PCB congeners, while
      meta- and para-substituted congeners had no significant effect. Two ortho
      substituted PCB congeners were chosen for the mechanistic studies, namely
      2,2',4,4'-TeCB and 2,2'-DCB, since they have been used in previous studies by
      others. In the absence of extracellular calcium, the respiratory burst in
      response to 2,2'-DCB and 2,2',4,4'-TeCB was reduced by 63% and 82%, respectively.
      Bisindolylmaleimide, which inhibits protein kinase C, reduced activated
      chemoluminescence by 2,2'-DCB, 2,2',4,4'-TeCB, N-formyl-methionyl-leucyl
      phenylalanine, and phorbol 12-myristate 13-acetate. Neomycin, which inhibits
      phospholipase C, had a slight, but significant, effect on the 2,2',4,4'-TeCB
      activated chemoluminescence but had a more pronounced effect on the 2,2'-DCB
      activated chemoluminescence. 2,2'-DCB and 2,2',4,4'-TeCB significantly increased
      phospholipase D (PLD) activity measured as the amount of 14C-phosphatidylbutanol
      formed. Ethanol (1%), a phospholipase D modulator, reduced the response to 2,2'
      DCB and 2,2',4,4'-TeCB by 72% and 75%, respectively. Furthermore, wortmannin (25
      nM), a phosphatidylinositol 3-kinase, and genistein, a more unspecific tyrosine
      kinase inhibitor, reduced chemoluminescence in response to PCB. In conclusion,
      our results indicate that PCB-activated chemoluminescence is dependent on the
      Ca(2+)-dependent phospholipase D or phospholipase C, phosphatidylinositol 3
      kinase, and protein kinase C activation prior to activation of the NADPH oxidase.
      Defects in neutrophhil functions upon exposure to PCB may render a greater
      susceptibility in the host to invading microorganisms or evoke inappropriate
      inflammatory responses leading to tissue injury.

PMID- 9653069
TI  - Effect of arsenite on induction of CYP1A and CYP2H in primary cultures of chick
      hepatocytes.
AB  - In earlier studies, treatment with sodium arsenite was shown to decrease total
      hepatic CYP in rats. A concomitant increase in heme oxygenase, the rate-limiting
      step in heme degradation to biliverdin, was considered responsible for the
      decrease in CYP. Here we investigated the effect of sodium arsenite on induction
      of CYP2H, CYP1A, and heme oxygenase in primary cultures of chicken embryo
      hepatocytes. When added simultaneously with inducer, arsenite inhibited
      phenobarbital-mediated increases in CYP2H and 3-methylcholanthrene-mediated
      increases in CYP1A, as measured enzymatically and immunochemically. Near maximal
      decreases were observed in these forms of CYP at a concentration of 2.5 microM
      sodium arsenite. The concentration-dependent decreases in CYP2H and CYP1A by
      sodium arsenite were concomitant with increases in heme oxygenase. Sodium
      arsenite was not toxic at concentrations as high as 10 microM, as indicated by
      protein synthesis and the reduction of MTT by intact cells. Sodium arsenite had
      no effect on induction of CYP2H1 mRNA, suggesting that the decreases in this form
      of CYP occurred post-transcriptionally. Treatment of cells with tin mesoporphyrin
      (SnMeso), an inhibitor of heme oxygenase, resulted in inhibition of arsenite
      induced heme oxygenase. However, SnMeso did not alter the effect of arsenite to
      prevent phenobarbital-mediated increases in CYP2H protein. SnMeso alone inhibited
      phenobarbital-mediated increases in CYP2H. Inclusion of 2 or 5 microM exogenous
      heme with arsenite did not prevent the arsenite-mediated decrease in CYP2H.
      Combined treatment with heme and phenobarbital induced heme oxygenase to the same
      extent as treatment with heme, arsenite, and phenobarbital. However, CYP2H
      activity was decreased only when the treatment included arsenite. These results
      suggest that elevated levels of heme oxygenase alone are not responsible for
      arsenite-mediated decreases in CYP2H.

PMID- 9653070
TI  - Reproductive toxicity and tissue concentrations of low doses of 2,3,7,8
      tetrachlorodibenzo-p-dioxin in male offspring rats exposed throughout pregnancy
      and lactation.
AB  - The effects of low doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the
      reproductive system of male offspring rats were examined. The dams were treated
      subcutaneously 2 weeks prior to mating and throughout mating, pregnancy, and
      lactation. They received an initial loading dose of 25, 60, or 300 ng TCDD/kg
      body wt, followed by a weekly maintenance dose of 5, 12, or 60 ng TCCD/kg body wt
      (TCDD 25/5, TCDD 60/12, and TCDD 300/60). Three dams per group were killed on
      Gestation Day 21 and the fetuses were removed. The concentration of TCDD in the
      maternal liver and fat was measured. After birth, developmental landmarks in male
      rats were monitored. At weaning, the concentration of TCDD in the offspring liver
      and testis was determined. Effects on male reproduction were studied on Postnatal
      Days (PND) 70 and 170. At weaning, the concentration of TCDD in the offspring
      liver was 0.24, 0.39, and 1.78 ng/g in the TCDD 25/5, TCDD 60/12, and TCDD 300/60
      groups, respectively. In the testes, the concentration of TCDD was 0.25 ng/g in
      the TCDD 25/5 and TCDD 60/12 groups and 0.28 ng/g in the TCDD 300/60 group. The
      number of sperm per cauda epididymis was reduced in TCDD groups at puberty and at
      adulthood. Daily sperm production was permanently decreased as was the sperm
      transit rate in the TCDD-exposed male rats, thus increasing the time required by
      the sperm to pass through the cauda epididymis. Moreover, the male rats of the
      TCDD groups showed an increased number of abnormal sperm when investigated at
      adulthood. Similarly, mounting and intromission latencies were significantly
      increased in the TCDD 25/5 and TCDD 300/60 groups. In the highest dose group,
      serum testosterone concentration was decreased at adulthood. Likewise, in this
      dose group permanent changes including pyknotic nuclei and the occurrence of cell
      debris in the lumen were revealed. The lowest adverse effect level and the no
      observed effect level can be estimated to be substantially lower than the
      estimated daily dose of the lowest dose which is 0.8 ng/kg body wt/day. Sperm
      parameters were more susceptible than the other end points investigated. However,
      the question as to whether such doses exposed throughout gestation and lactation
      induce subtle changes in humans remains to be determined.

PMID- 9653071
TI  - Effect of a dopamine agonist on luteinizing hormone receptors, cyclic AMP
      production and steroidogenesis in rat Leydig cells.
AB  - Dopamine agonists are known to increase the incidence of Leydig cell
      hyperplasia/adenomas when administered to rats over periods of 1-2 years. We have
      examined the early changes in factors affecting luteinizing hormone (LH)
      controlled signal transduction pathways and steroidogenesis in Leydig cells in
      vitro after chronic oral administration of one of these dopamine agonists,
      Mesulergine (CU327-085) (N-(1-6,dimethylergolin-8a-yl)-N',N'-dimethylsulphamide
      hydrochloride) to Sprague-Dawley (SD) rats. Eight-week-old rats were given this
      dopamine agonist (2 mg/kg body wt/day) in food for 1, 5, or 12 weeks. The Leydig
      cells from control and treated rats were purified by elutriation and density
      gradient centrifugation. The dopamine agonist treatment was found to decrease the
      specific binding of 125I-human chorionic gonadotrophin (hCG) binding to the
      Leydig cells: a decrease was detected as early as 1 week after treatment and was
      more pronounced after 5 and 12 weeks. This was found to be due to a decrease in
      the LH/hCG receptor numbers and not to a decrease in LH/hCG-receptor binding
      affinity. Both basal and LH-stimulated cAMP and testosterone production were also
      decreased; cAMP production was decreased by approximately 50% by all
      concentrations of LH added whereas testosterone production was only decreased
      with submaximum stimulating concentrations of LH. The formation of testosterone
      in response to dibutyryl cAMP was also decreased by approximately 50%, indicating
      additional lesions in the signal transduction pathway. The addition of the cell
      permeant 22R-hydroxycholesterol (22R) demonstrated that testosterone but not
      pregnenolone production was decreased by treatment with the dopamine agonist,
      thus indicating that the 17 alpha-hydroxylase/C17-20 lyase may have been
      inhibited. Supporting evidence for this was found because the dopamine agonist
      also increased aromatase activity in the Leydig cells and thus the potential to
      produce estrogens; previous studies have shown that estradiol is an inhibitor of
      the 17-20 lyase enzyme. The addition of the dopamine agonist directly to the
      Leydig cells did not inhibit cAMP production or testosterone production except at
      high concentrations. It is concluded that treatment of rats with the dopamine
      agonist indirectly (i.e., via the pituitary) affects Leydig cell function
      resulting in a rapid decrease in LH receptors and cAMP and testosterone
      production. Aromatase activity is increased and thus the capacity to produce
      estrogens. These early changes in the signal transduction pathways and
      steroidogenesis may be involved in the Leydig cell hyperplasia/adenoma formation
      that subsequently occurs.

PMID- 9653072
TI  - Urinary physiologic and chemical metabolic effects on the urothelial cytotoxicity
      and potential DNA adducts of o-phenylphenol in male rats.
AB  - ortho-Phenylphenol (OPP), a fungicide and antibacterial agent with food residues,
      is carcinogenic to rat bladder. The present studies provide information on
      changes in urinary composition and urinary metabolites, urothelial cytotoxicity
      and regenerative hyperplasia, and DNA adducts in male F344 rats fed OPP. An
      initial experiment evaluated dietary doses of 0, 1,000, 4,000, and 12,500 ppm OPP
      fed for 13 weeks. There was no evidence of urinary calculi, microcrystalluria, or
      calcium phosphate-containing precipitate, but urothelial cytotoxicity and
      hyperplasia occurred at the highest dose only. In a second experiment, rats were
      fed dietary OPP levels of 0, 800, 4,000, 8,000, and 12,500 ppm. Urinary pH was >
      7 in all groups. Urinary volume was increased at the 2 highest doses with
      consequent decreases in osmolality, creatinine, and other solutes. Total urinary
      OPP metabolite excretions were increased, mostly excreted as conjugates of OPP
      and of phenylhydroquinone. Free OPP or free metabolites accounted for less than
      2% excreted in the urine without a dose response. Urothelial toxicity and
      hyperplasia occurred only at doses of 8,000 and 12,500 ppm. OPP-DNA adducts were
      not detected in the urothelium at any dose. In summary, OPP produces cytotoxicity
      and proliferation of the urothelium at dietary doses > or = 8,000 ppm without
      formation of urinary solids. The paucity of unconjugated metabolites and the lack
      of OPP-DNA adducts suggests that OPP is acting as a bladder carcinogen in male
      rats by inducing cytotoxicity and hyperplasia without it or its metabolites
      directly binding to DNA.

PMID- 9653073
TI  - A minimally toxic dose of methylene dianiline injures biliary epithelial cells in
      rats.
AB  - The threshold for hepatotoxicity and cholestasis induced by methylene dianiline
      (DAPM) in rats is between 25 and 75 mg/kg (Bailie et al., Environ. Health
      Perspect., 124, 25-30, 1993). Our objectives were to determine if a minimally
      toxic dose of DAPM provided a model system for studies of selective injury to
      biliary epithelial cells (BEC) in vivo. Thus, we examined the effects of 50 mg
      DAPM/kg on (1) biliary constituents, (2) liver constituents likely involved in
      DAPM biotransformation/detoxification, and (3) early morphological and
      histochemical changes in the liver. Male Sprague Dawley rats had biliary cannulas
      positioned under pentobarbital anesthesia. After 1 h of control bile collection,
      rats received 50 mg DAPM/kg po in 35% ethanol or 35% ethanol only. Bile was
      collected for another 6 h. Histochemical, ultrastructural, and biochemical liver
      alterations were assessed at 3 h or at 3 and 6 h. DAPM had minimal effects on
      biliary bile salt and bilirubin excretion over 6 h. Biliary glucose and protein
      excretion were increased approximately 2-fold starting in Hour 1, while inorganic
      phosphate excretion was not increased until Hour 2. Biliary glutathione excretion
      initially increased (Hour 1) but then declined steadily for 5 h. Microsomal
      cytochrome P-450 activities were transiently decreased at 3 h but had returned to
      control values by 6 h. Liver glutathione (GSH and GSSG) was not affected by DAPM
      at 3 or 6 h. Necrosis of intrahepatic bile ducts was severe at 6 h with moderate
      injury in smaller bile ducts. Ultrastructural alterations were observed in BEC
      mitochondria and microvilli at 3 h with no apparent alterations in hepatocyte
      mitochondria or tight junctions between cells. In addition, histochemical
      staining of liver sections and assays of mitochondrial enzyme activities in vitro
      at 3 h revealed no loss of mitochondrial function in hepatocytes. These results
      provide strong evidence for defining DAPM as a selective bile duct toxicant.

PMID- 9653074
TI  - Treatment of rats during pubertal development with 2,3,7,8-tetrachlorodibenzo-p
      dioxin alters both signaling kinase activities and epidermal growth factor
      receptor binding in the testis and the motility and acrosomal reaction of sperm.
AB  - Different doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (0.1, 1, 5, and 10
      micrograms/kg body wt) were administered i.p. to 21-day-old male Sprague-Dawley
      rats. Control animals received the same volume of the vehicle (acetone:corn oil,
      1:19). Body weight and daily food intake were recorded during the 90-day time
      course of the study. Random samples of five rats were sacrificed at 34, 49, 62,
      and 90 days of age. Epidermal growth factor receptor (EGFR) in whole testis was
      measured, as were the activities of c-Src kinase, protein tyrosine kinase (PTK),
      mitogen-activated protein 2 kinase (MAP2K also termed as Erk2), protein kinase A
      (PKA), and protein kinase C (PKC). Testicular tissue from 90-day-old rats was
      evaluated for histopathology, and sperm numbers in whole testis were counted to
      estimate daily sperm production. The motility of sperm in the vas deferens and
      caudal segments of the epididymis of 90-day-old rats was measured by computer
      assisted sperm analysis (CASA) and the function of the sperm was tested by
      assessment of acrosome reactions. A dose of 10 micrograms/kg resulted in
      testicular atrophy and histopathologic examination revealed a decrease in the
      diameter of the seminiferous tubules. Sertoli cell nuclei were clearly seen, but
      the spermatogonial population was totally absent. Lower doses of TCDD did not
      affect testicular histology, but doses as low as 1 microgram/kg significantly
      decreased testicular sperm numbers and affected some sperm functions (motility
      parameters and acrosome reactions) in 90-day-old rats. Significant decreases in
      EGFR were found in 34-day-old rats and this effect on EGFR was sustained until
      the end of the experiment (90 days). Although TCDD significantly increased c-Src
      kinase activity in immature and mature rats, opposite effects of TCDD on
      activities of PTK, PKA, and PKC were found in 34-day-old rats vs 49-, 62-, and 90
      day-old rats. When 10 micrograms TCDD/kg was administered to 21-day-old rat, 24-h
      after c-Src kinase inhibitor geldanamycin, there was no testicular atrophy and no
      change in the daily sperm production was found. These findings provide evidence
      for involvement of Src kinase signaling and EGFR in the mechanism by which TCDD
      disrupts testicular development and subsequently affects testis function.

PMID- 9653077
TI  - Chemical Index for Volume 150
AB  - Copyright

PMID- 9653075
TI  - Chemical-induced hepatocyte ploidy.

PMID- 9653078
TI  - Medullary thymic epithelium: a mosaic of epithelial "self"?

PMID- 9653079
TI  - CD4 T cell tolerance to human C-reactive protein, an inducible serum protein, is
      mediated by medullary thymic epithelium.
AB  - Inducible serum proteins whose concentrations oscillate between nontolerogenic
      and tolerogenic levels pose a particular challenge to the maintenance of self
      tolerance. Temporal restrictions of intrathymic antigen supply should prevent
      continuous central tolerization of T cells, in analogy to the spatial limitation
      imposed by tissue-restricted antigen expression. Major acute-phase proteins such
      as human C-reactive protein (hCRP) are typical examples for such inducible self
      antigens. The circulating concentration of hCRP, which is secreted by
      hepatocytes, is induced up to 1,000-fold during an acute-phase reaction. We have
      analyzed tolerance to hCRP expressed in transgenic mice under its autologous
      regulatory regions. Physiological regulation of basal levels (<10(-9) M) and
      inducibility (>500-fold) are preserved in female transgenics, whereas male
      transgenics constitutively display induced levels. Surprisingly, crossing of hCRP
      transgenic mice to two lines of T cell receptor transgenic mice (specific for
      either a dominant or a subdominant epitope) showed that tolerance is mediated by
      intrathymic deletion of immature thymocytes, irrespective of widely differing
      serum levels. In the absence of induction, hCRP expressed by thymic medullary
      epithelial cells rather than liver-derived hCRP is necessary and sufficient to
      induce tolerance. Importantly, medullary epithelial cells also express two
      homologous mouse acute-phase proteins. These results support a physiological role
      of "ectopic" thymic expression in tolerance induction to acute-phase proteins and
      possibly other inducible self-antigens and have implications for delineating the
      relative contributions of central versus peripheral tolerance.

PMID- 9653080
TI  - Cloning of vascular adhesion protein 1 reveals a novel multifunctional adhesion
      molecule.
AB  - Vascular adhesion protein 1 (VAP-1) is a human endothelial sialoglycoprotein
      whose cell surface expression is induced under inflammatory conditions. It has
      been shown previously to participate in lymphocyte recirculation by mediating the
      binding of lymphocytes to peripheral lymph node vascular endothelial cells in an
      L-selectin-independent fashion. We report here that the VAP-1 cDNA encodes a type
      II transmembrane protein of 84.6 kD with a single transmembrane domain located at
      the NH2-terminal end of the molecule and six potential N-glycosylation sites in
      the extracellular domain. In vivo, the protein exists predominantly as a
      homodimer of 170-180 kD. Ax endothelial cells transfected with a VAP-1 cDNA
      express VAP-1 on their cell surface and bind lymphocytes, and the binding can be
      partially inhibited with anti-VAP-1 mAbs. VAP-1 has no similarity to any
      currently known adhesion molecules, but has significant identity to the copper
      containing amine oxidase family and has a monoamine oxidase activity. We propose
      that VAP-1 is a novel type of adhesion molecule with dual function. With the
      appropriate glycosylation and in the correct inflammatory setting, its expression
      on the lumenal endothelial cell surface allows it to mediate lymphocyte adhesion
      and to function as an adhesion receptor involved in lymphocyte recirculation. Its
      primary function in other locations where it is expressed, such as smooth muscle,
      may depend on its inherent monoamine oxidase activity.

PMID- 9653081
TI  - Immunization with a peptide surrogate for double-stranded DNA (dsDNA) induces
      autoantibody production and renal immunoglobulin deposition.
AB  - Anti-double-stranded DNA (dsDNA) antibodies are the serologic abnormality
      characteristically associated with systemic lupus erythematosus (SLE) and may
      play an important role in disease pathogenesis. Although the anti-dsDNA
      antibodies present in SLE are indicative of an antigen-driven response, the
      antigen has not been conclusively identified. By screening a phage peptide
      display library, we demonstrated previously that the decapeptide DWEYSVWLSN is
      specifically bound by the pathogenic murine IgG2b anti-dsDNA antibody R4A. To
      investigate the possibility that a protein antigen might trigger lupus-like
      autoimmunity, we immunized BALB/c mice with DWEYSVWLSN in adjuvant. Mice
      developed significant titers of IgG anti-dsDNA antibodies 2-3 wk after the
      initial immunization. Immunized mice also developed antibodies against some other
      lupus autoantigens, and immunoglobulin deposition was present in renal glomeruli
      at 49 d. Although an immune response to peptide and dsDNA was evident in BALB/c
      mice, there was little response in other inbred strains. This study demonstrates
      that lupus-like anti-dsDNA reactivity can be generated in nonautoimmune mice by
      immunization with a peptide antigen. Peptide-induced autoimmunity may prove
      useful in understanding the spreading of antigenic specificities targeted in SLE.
      However, most importantly, the demonstration that a peptide antigen can initiate
      a SLE-like immune response opens a new chapter on the potential antigenic stimuli
      that might trigger SLE.

PMID- 9653082
TI  - Transforming growth factor beta production is inversely correlated with severity
      of murine malaria infection.
AB  - We have examined the role of the immunomodulatory cytokine transforming growth
      factor (TGF)-beta in the resolution and pathology of malaria in BALB/c mice.
      Circulating levels of TGF-beta, and production of bioactive TGF-beta by
      splenocytes, were found to be low in lethal infections with Plasmodium berghei.
      In contrast, resolving infections with P. chabaudi chabaudi or P. yoelii were
      accompanied by significant TGF-beta production. A causal association between the
      failure to produce TGF-beta and the severity of malaria infection was
      demonstrated by treatment of infected mice with neutralizing antibody to TGF
      beta, which exacerbated the virulence of P. berghei and transformed a resolving
      P. chabaudi chabaudi infection into a lethal infection, but had little effect on
      the course of P. yoelii infection. Parasitemia increased more rapidly in anti-TGF
      beta-treated mice but this did not seem to be the explanation for the increased
      pathology of infection as peak parasitemias were unchanged. Treatment of P.
      berghei-infected mice with recombinant TGF-beta (rTGF-beta) slowed the rate of
      parasite proliferation and prolonged their survival from 15 to up to 35 d. rTGF
      beta treatment was accompanied by a significant decrease in serum tumor necrosis
      factor alpha and an increase in interleukin 10. Finally, we present evidence that
      differences in TGF-beta responses in different malaria infections are due to
      intrinsic differences between species of malaria parasites in their ability to
      induce production of TGF-beta. Thus, TGF-beta seems to induce protective immune
      responses, leading to slower parasite growth, early in infection, and,
      subsequently, appears to downregulate pathogenic responses late in infection.
      This duality of effect makes TGF-beta a prime candidate for a major
      immunomodulatory cytokine associated with successful control of malaria
      infection.

PMID- 9653083
TI  - Phase-variable expression of lipopolysaccharide contributes to the virulence of
      legionella pneumophila.
AB  - With the aid of monoclonal antibody (mAb) 2625, raised against the
      lipopolysaccharide (LPS) of Legionella pneumophila serogroup 1, subgroup OLDA, we
      isolated mutant 811 from the virulent wild-type strain RC1. This mutant was not
      reactive with mAb 2625 and exhibited an unstable phenotype, since we observed an
      in vitro and in vivo switch of mutant 811 to the mAb 2625-positive phenotype,
      thus restoring the wild-type LPS. Bactericidal assays revealed that mutant 811
      was lysed by serum complement components, whereas the parental strain RC1 was
      almost serum resistant. Moreover, mutant 811 was not able to replicate
      intracellularly in macrophage-like cell line HL-60. In the guinea pig animal
      model, mutant 811 exhibited significantly reduced ability to replicate. Among
      recovered bacteria, mAb 2625-positive revertants were increased by fourfold. The
      relevance of LPS phase switch for pathogenesis of Legionella infection was
      further corroborated by the observation that 5% of the bacteria recovered from
      the lungs of guinea pigs infected with the wild-type strain RC1 were negative for
      mAb 2625 binding. These findings strongly indicate that under in vivo conditions
      switching between two LPS phenotypes occurs and may promote adaptation and
      replication of L. pneumophila. This is the first description of phase-variable
      expression of Legionella LPS.

PMID- 9653084
TI  - Evolution of a complex T cell receptor repertoire during primary and recall
      bacterial infection.
AB  - The mechanisms underlying the genesis and maintenance of T cell memory remain
      unclear. In this study, we examined the evolution of a complex, antigen-specific
      T cell population during the transition from primary effector to memory T cells
      after Listeria monocytogenes infection. T cell populations specific for
      listeriolysin O (LLO)91-99, the immunodominant epitope recognized by H2-Kd
      restricted T lymphocytes, were directly identified in immune spleens using
      tetrameric H2-Kd-epitope complexes. The T cell receptor (TCR) Vbeta repertoire of
      specific T cells was determined by direct, ex vivo staining with a panel of mAbs.
      We demonstrate that LLO91-99-specific, primary effector T cell populations have a
      diverse TCR Vbeta repertoire. Analyses of memory T cell populations demonstrated
      similar TCR diversity. Furthermore, experiments with individual mice demonstrated
      that primary effector and memory T cells have indistinguishable TCR repertoires.
      Remarkably, after reinfection with L. monocytogenes, LLO91-99-specific T cells
      have a narrower TCR repertoire than do primary effector or memory T cells. Thus,
      our studies show that the TCR repertoire of primary effector T lymphocytes is
      uniformly transmitted to memory T cells, whereas expansion of memory T cells is
      selective.

PMID- 9653085
TI  - Conserved T cell receptor repertoire in primary and memory CD8 T cell responses
      to an acute viral infection.
AB  - Viral infections often induce potent CD8 T cell responses that play a key role in
      antiviral immunity. After viral clearance, the vast majority of the expanded CD8
      T cells undergo apoptosis, leaving behind a stable number of memory cells. The
      relationship between the CD8 T cells that clear the acute viral infection and the
      long-lived CD8 memory pool remaining in the individual is not fully understood.
      To address this issue, we examined the T cell receptor (TCR) repertoire of virus
      specific CD8 T cells in the mouse model of infection with lymphocytic
      choriomeningitis virus (LCMV) using three approaches: (a) in vivo quantitative
      TCR beta chain V segment and complementarity determining region 3 (CDR3) length
      repertoire analysis by spectratyping (immunoscope); (b) identification of LCMV
      specific CD8 T cells with MHC class I tetramers containing viral peptide and
      costaining with TCR Vbeta-specific antibodies; and (c) functional TCR
      fingerprinting based on recognition of variant peptides. We compared the
      repertoire of CD8 T cells responding to acute primary and secondary LCMV
      infections, together with that of virus-specific memory T cells in immune mice.
      Our analysis showed that CD8 T cells from several Vbeta families participated in
      the anti-LCMV response directed to the dominant cytotoxic T lymphocyte (CTL)
      epitope (NP118-126). However, the bulk (approximately 70%) of this CTL response
      was due to three privileged T cell populations systematically expanding during
      LCMV infection. Approximately 30% of the response consisted of Vbeta10+ CD8 T
      cells with a beta chain CDR3 length of nine amino acids, and 40% consisted of
      Vbeta8.1+ (beta CDR3 = eight amino acids) and Vbeta8.2+ cells (beta CDR3 = six
      amino acids). Finally, we showed that the TCR repertoire of the primary antiviral
      CD8 T cell response was similar both structurally and functionally to that of the
      memory pool and the secondary CD8 T cell effectors. These results suggest a
      stochastic selection of memory cells from the pool of CD8 T cells activated
      during primary infection.

PMID- 9653086
TI  - Induction of HIV-1 replication in latently infected CD4+ T cells using a
      combination of cytokines.
AB  - Although it has been demonstrated that certain cytokines, particularly
      proinflammatory cytokines, can enhance ongoing viral replication in peripheral
      blood mononuclear cells (PBMCs) of HIV-1-infected individuals, it is unclear what
      role these cytokines play in the induction of HIV-1 replication in latently
      infected, resting CD4(+) T cells. This study demonstrates that the in vitro
      combination of the proinflammatory cytokines interleukin (IL)-6 and tumor
      necrosis factor (TNF)-alpha together with the immunoregulatory cytokine IL-2 are
      potent inducers of viral replication in highly purified, latently infected,
      resting CD4+ T cells derived from HIV-infected individuals who are antiretroviral
      therapy-naive as well as those who are receiving highly active antiretroviral
      therapy (HAART). Viral replication induced by this combination of cytokines was
      completely suppressed in the presence of HAART in vitro. Given that an array of
      cytokines, including IL-6, TNF-alpha, and IL-2, are copiously expressed in the
      microenvironment of the lymphoid tissues, which harbor the latent viral
      reservoirs, induction of HIV by this combination of cytokines may in part explain
      the commonly observed reappearance of detectable plasma viremia in HIV-infected
      individuals in whom HAART was discontinued. Moreover, since it is likely that
      these infected cells die upon activation of virus and that HAART prevents spread
      of virus to adjacent cells, the observation that this combination of cytokines
      can markedly induce viral replication in this reservoir may have important
      implications for the activation-mediated diminution of the latent reservoir of
      HIV in patients receiving HAART.

PMID- 9653087
TI  - The molecular mechanism of B cell activation by toll-like receptor protein RP
      105.
AB  - The B cell-specific transmembrane protein RP-105 belongs to the family of
      Drosophila toll-like proteins which are likely to trigger innate immune responses
      in mice and man. Here we demonstrate that the Src-family protein tyrosine kinase
      Lyn, protein kinase C beta I/II (PKCbetaI/II), and Erk2-specific mitogen
      activated protein (MAP) kinase kinase (MEK) are essential and probably
      functionally connected elements of the RP-105-mediated signaling cascade in B
      cells. We also find that negative regulation of RP-105-mediated activation of MAP
      kinases by membrane immunoglobulin may account for the phenomenon of antigen
      receptor-mediated arrest of RP-105-mediated B cell proliferation.

PMID- 9653088
TI  - Distinct methylation of the interferon gamma (IFN-gamma) and interleukin 3 (IL-3)
      genes in newly activated primary CD8+ T lymphocytes: regional IFN-gamma promoter
      demethylation and mRNA expression are heritable in CD44(high)CD8+ T cells.
AB  - Differential genomic DNA methylation has the potential to influence the
      development of T cell cytokine production profiles. Therefore, we have conducted
      a clonal analysis of interferon (IFN)-gamma and interleukin (IL)-3 gene
      methylation and messenger (m)RNA expression in primary CD8+ T cells during the
      early stages of activation, growth, and cytokine expression. Despite similar
      distributions and densities of CpG methylation sites, the IFN-gamma and IL-3
      promoters exhibited differential demethylation in the same T cell clone, and
      heterogeneity between clones. Methylation patterns and mRNA levels were
      correlated for both genes, but demethylation of the IFN-gamma promoter was
      widespread across >300 basepairs in clones expressing high levels of IFN-gamma
      mRNA, whereas demethylation of the IL-3 promoter was confined to specific CpG
      sites in the same clones. Conversely, the majority of clones expressing low or
      undetectable levels of IFN-gamma mRNA exhibited symmetrical methylation of four
      to six of the IFN-gamma promoter CpG sites. Genomic DNA methylation also has the
      potential to influence the maintenance or stability of T cell cytokine production
      profiles. Therefore, we also tested the heritability of IFN-gamma gene
      methylation and mRNA expression in families of clones derived from resting
      CD44(low)CD8+ T cells or from previously activated CD44(high)CD8+ T cells. The
      patterns of IFN-gamma gene demethylation and mRNA expression were faithfully
      inherited in all clones derived from CD44(high) cells, but variable in clones
      derived from CD44(low) cells. Overall, these findings suggest that differential
      genomic DNA methylation, including differences among cytokine genes, among
      individual T cells, and among T cells with different activation histories, is an
      important feature of cytokine gene expression in primary T cells.

PMID- 9653089
TI  - Spontaneous skin ulceration and defective T cell function in CD18 null mice.
AB  - A null mutation was prepared in the mouse for CD18, the beta2 subunit of
      leukocyte integrins. Homozygous CD18 null mice develop chronic dermatitis with
      extensive facial and submandibular erosions. The phenotype includes elevated
      neutrophil counts, increased immunoglobulin levels, lymphadenopathy,
      splenomegaly, and abundant plasma cells in skin, lymph nodes, gut, and kidney.
      Very few neutrophils were found in spontaneously occurring skin lesions or with
      an induced toxic dermatitis. Intravital microscopy in CD18 null mice revealed a
      lack of firm neutrophil attachment to venules in the cremaster muscle in response
      to N-formyl- methionyl-leucyl-phenylalanine. A severe defect in T cell
      proliferation was found in the CD18 null mice when T cell receptors were
      stimulated either by staphylococcal enterotoxin A or by major histocompatibility
      complex alloantigens demonstrating a greater role of CD11/CD18 integrins in T
      cell responses than previously documented. The null mice are useful for
      delineating the functions of CD18 in vivo.

PMID- 9653090
TI  - Interferon gamma-independent rejection of interleukin 12-transduced carcinoma
      cells requires CD4+ T cells and Granulocyte/Macrophage colony-stimulating factor.
AB  - We analyzed the ability of interferon (IFN)-gamma knockout mice (GKO) to reject a
      colon carcinoma transduced with interleukin (IL)-12 genes (C26/IL-12). Although
      the absence of IFN-gamma impaired the early response and reduced the time to
      tumor onset in GKO mice, the overall tumor take rate was similar to that of
      BALB/c mice. In GKO mice, C26/IL-12 tumors had a reduced number of infiltrating
      leukocytes, especially CD8 and natural killer cells. Analysis of the tumor site,
      draining nodes, and spleens of GKO mice revealed reduced expression of IFN-
      inducible protein 10 and monokine induced by gamma-IFN. Despite these defects,
      GKO mice that rejected C26/IL-12 tumor, and mice that were primed in vivo with
      irradiated C26/IL-12 cells, showed the same cytotoxic T lymphocyte activity but
      higher production of granulocyte/macrophage colony-stimulating factor (GM-CSF) as
      compared with control BALB/c mice. Treatment with monoclonal antibodies against
      GM-CSF abrogated tumor regression in GKO but not in BALB/c mice. CD4 T
      lymphocytes, which proved unnecessary or suppressive during rejection of C26/IL
      12 cells in BALB/c mice, were required for tumor rejection in GKO mice. CD4 T
      cell depletion was coupled with a decline in GM-CSF expression by lymphocytes
      infiltrating the tumors or in the draining nodes, and with the reduction and
      disappearance of granulocytes and CD8 T cells, respectively, in tumor nodules.
      These results suggest that GM-CSF can substitute for IFN-gamma in maintaining the
      CD8-polymorphonuclear leukocyte cross-talk that is a hallmark of tumor rejection.

PMID- 9653091
TI  - Antiviral protection and germinal center formation, but impaired B cell memory in
      the absence of CD19.
AB  - Coligation of CD19, a molecule expressed during all stages of B cell development
      except plasmacytes, lowers the threshold for B cell activation with anti-IgM by a
      factor of 100. The cytoplasmic tail of CD19 contains nine tyrosine residues as
      possible phosphorylation sites and is postulated to function as the signal
      transducing element for complement receptor (CR)2. Generation and analysis of
      CD19 gene-targeted mice revealed that T cell-dependent (TD) antibody responses to
      proteinaceous antigens were impaired, whereas those to T cell-independent (TI)
      type 2 antigens were normal or even augmented. These results are compatible with
      earlier complement depletion studies and the postulated function of CD19. To
      analyze the role of CD19 in antiviral antibody responses, we immunized CD19(-/-)
      mice with viral antigens of TI-1, TI-2, and TD type. The effect of CD19 on TI
      responses was more dependent on antigen dose and replicative capacity than on
      antigen type. CR blocking experiments confirmed the role of CD19 as B cell signal
      transducer for complement. In contrast to immunization with protein antigens,
      infection of CD19(-/-) mice with replicating virus led to generation of specific
      germinal centers, which persisted for >100 d, whereas maintenance of memory
      antibody titers as well as circulating memory B cells was fully dependent on
      CD19. Thus, our study confirms a costimulatory role of CD19 on B cells under
      limiting antigen conditions and indicates an important role for B cell memory.

PMID- 9653092
TI  - The coordinated action of CC chemokines in the lung orchestrates allergic
      inflammation and airway hyperresponsiveness.
AB  - The complex pathophysiology of lung allergic inflammation and bronchial
      hyperresponsiveness (BHR) that characterize asthma is achieved by the regulated
      accumulation and activation of different leukocyte subsets in the lung. The
      development and maintenance of these processes correlate with the coordinated
      production of chemokines. Here, we have assessed the role that different
      chemokines play in lung allergic inflammation and BHR by blocking their
      activities in vivo. Our results show that blockage of each one of these
      chemokines reduces both lung leukocyte infiltration and BHR in a substantially
      different way. Thus, eotaxin neutralization reduces specifically BHR and lung
      eosinophilia transiently after each antigen exposure. Monocyte chemoattractant
      protein (MCP)-5 neutralization abolishes BHR not by affecting the accumulation of
      inflammatory leukocytes in the airways, but rather by altering the trafficking of
      the eosinophils and other leukocytes through the lung interstitium.
      Neutralization of RANTES (regulated upon activation, normal T cell expressed and
      secreted) receptor(s) with a receptor antagonist decreases significantly
      lymphocyte and eosinophil infiltration as well as mRNA expression of eotaxin and
      RANTES. In contrast, neutralization of one of the ligands for RANTES receptors,
      macrophage-inflammatory protein 1alpha, reduces only slightly lung eosinophilia
      and BHR. Finally, MCP-1 neutralization diminishes drastically BHR and
      inflammation, and this correlates with a pronounced decrease in monocyte- and
      lymphocyte-derived inflammatory mediators. These results suggest that different
      chemokines activate different cellular and molecular pathways that in a
      coordinated fashion contribute to the complex pathophysiology of asthma, and that
      their individual blockage results in intervention at different levels of these
      processes.

PMID- 9653093
TI  - B lymphocytes producing demyelinating autoantibodies: development and function in
      gene-targeted transgenic mice.
AB  - We studied the cellular basis of self tolerance of B cells specific for brain
      autoantigens using transgenic mice engineered to produce high titers of
      autoantibodies against the myelin oligodendrocyte glycoprotein (MOG), a surface
      component of central nervous system myelin. We generated "knock-in" mice by
      replacing the germline JH locus with the rearranged immunoglobulin (Ig) H chain
      variable (V) gene of a pathogenic MOG-specific monoclonal antibody. In the
      transgenic mice, conventional B cells reach normal numbers in bone marrow and
      periphery and express exclusively transgenic H chains, resulting in high titers
      of MOG-specific serum Igs. Additionally, about one third of transgenic B cells
      bind MOG, thus demonstrating the absence of active tolerization. Furthermore,
      peritoneal B-1 lymphocytes are strongly depleted. Upon immunization with MOG, the
      mature transgenic B cell population undergoes normal differentiation to plasma
      cells secreting MOG-specific IgG antibodies, during which both Ig isotype
      switching and somatic mutation occur. In naive transgenic mice, the presence of
      this substantial autoreactive B cell population is benign, and the mice fail to
      develop either spontaneous neurological disease or pathological evidence of
      demyelination. However, the presence of the transgene both accelerates and
      exacerbates experimental autoimmune encephalitis, irrespective of the identity of
      the initial autoimmune insult.

PMID- 9653094
TI  - Epstein-Barr virus-induced molecule 1 ligand chemokine is expressed by dendritic
      cells in lymphoid tissues and strongly attracts naive T cells and activated B
      cells.
AB  - Movement of T and B lymphocytes through secondary lymphoid tissues is likely to
      involve multiple cues that help the cells navigate to appropriate compartments.
      Epstein-Barr virus- induced molecule 1 (EBI-1) ligand chemokine (ELC/MIP3beta) is
      expressed constitutively within lymphoid tissues and may act as such a guidance
      cue. Here, we have isolated mouse ELC and characterized its expression pattern
      and chemotactic properties. ELC is expressed constitutively in dendritic cells
      within the T cell zone of secondary lymphoid tissues. Recombinant ELC was
      strongly chemotactic for naive (L-selectinhi) CD4 T cells and for CD8 T cells and
      weakly attractive for resting B cells and memory (L-selectinlo) CD4 T cells.
      After activation through the B cell receptor, the chemotactic response of B cells
      was enhanced. Like its human counterpart, murine ELC stimulated cells transfected
      with EBI-1/CC chemokine receptor 7 (CCR7). Our findings suggest a central role
      for ELC in promoting encounters between recirculating T cells and dendritic cells
      and in the migration of activated B cells into the T zone of secondary lymphoid
      tissues.

PMID- 9653095
TI  - In vivo inhibition of CC and CX3C chemokine-induced leukocyte infiltration and
      attenuation of glomerulonephritis in Wistar-Kyoto (WKY) rats by vMIP-II.
AB  - Chemokines play a central role in immune and inflammatory responses. It has been
      observed recently that certain viruses have evolved molecular piracy and mimicry
      mechanisms by encoding and synthesizing proteins that interfere with the normal
      host defense response. One such viral protein, vMIP-II, encoded by human
      herpesvirus 8, has been identified with in vitro antagonistic activities against
      CC and CXC chemokine receptors. We report here that vMIP-II has additional
      antagonistic activity against CX3CR1, the receptor for fractalkine. To
      investigate the potential therapeutic effect of this broad-spectrum chemokine
      antagonist, we studied the antiinflammatory activity of vMIP-II in a rat model of
      experimental glomerulonephritis induced by an antiglomerular basement membrane
      antibody. vMIP-II potently inhibited monocyte chemoattractant protein 1-,
      macrophage inflammatory protein 1beta-, RANTES (regulated on activation, normal T
      cell expressed and secreted)-, and fractalkine-induced chemotaxis of activated
      leukocytes isolated from nephritic glomeruli, significantly reduced leukocyte
      infiltration to the glomeruli, and markedly attenuated proteinuria. These results
      suggest that molecules encoded by some viruses may serve as useful templates for
      the development of antiinflammatory compounds.

PMID- 9653096
TI  - Cytotoxic T lymphocyte antigen 4 (CTLA4) blockade accelerates the acute rejection
      of cardiac allografts in CD28-deficient mice: CTLA4 can function independently of
      CD28.
AB  - Cytotoxic T lymphocyte antigen 4 (CTLA4) appears to negatively regulate T cell
      activation. One mechanism by which CTLA4 might antagonize T cell function is
      through inhibition of CD28 signaling by competing for their shared ligands B7-1
      and B7-2. In addition, CTLA4 ligation could initiate a signaling cascade that
      inhibits T cell activation. To address whether CTLA4 could inhibit immune
      responses in the absence of CD28, rejection of heart allografts was studied in
      CD28-deficient mice. H-2(q) hearts were transplanted into allogeneic wild-type or
      CD28-deficient mice (H-2(b)). Graft rejection was delayed in CD28-deficient
      compared with wild-type mice. Treatment of wild-type recipients with CTLA4
      immunoglobulin (Ig), or with anti-B7-1 plus anti-B7-2 mAbs significantly
      prolonged allograft survival. In contrast, treatment of CD28-deficient mice with
      CTLA4-Ig, anti-B7-1 plus anti-B7-2 mAbs, or a blocking anti-CTLA4 mAb induced
      acceleration of allograft rejection. This increased rate of graft rejection was
      associated with more severe mononuclear cell infiltration and enhanced levels of
      IFN-gamma and IL-6 transcripts in donor hearts of untreated wild-type and CTLA4
      Ig- or anti-CTLA4 mAb-treated CD28-deficient mice. Thus, the negative regulatory
      role of CTLA4 extends beyond its potential ability to prevent CD28 activation
      through ligand competition. Even in the absence of CD28, CTLA4 plays an
      inhibitory role in the regulation of allograft rejection.

PMID- 9653097
TI  - B7-1 engagement of cytotoxic T lymphocyte antigen 4 inhibits T cell activation in
      the absence of CD28.
AB  - Ligation of cytotoxic T lymphocyte antigen 4 (CTLA4) appears to inhibit T cell
      responses. Four mechanisms have been proposed to explain the inhibitory activity
      of CTLA4: competition for B7-1 and B7-2 binding by CD28; sequestration of
      signaling molecules away from CD28 via endocytosis; delivery of a signal that
      antagonizes a CD28 signal; and delivery of a signal that antagonizes a T cell
      receptor (TCR) signal. As three of these potential mechanisms involve functional
      antagonism of CD28, an experimental model was designed to determine whether CTLA4
      could inhibit T cell function in the absence of CD28. TCR transgenic/recombinase
      activating gene 2-deficient/CD28-wild-type or CD28-deficient mice were generated
      and immunized with an antigen-expressing tumor. Primed T cells from both types of
      mice produced cytokines and proliferated in response to stimulator cells lacking
      B7 expression. However, whereas the response of CD28+/+ T cells was augmented by
      costimulation with B7-1, the response of the CD28-/- T cells was strongly
      inhibited. This inhibition was reversed by monoclonal antibody against B7-1 or
      CTLA4. Thus, CTLA4 can potently inhibit T cell activation in the absence of CD28,
      indicating that antagonism of a TCR-mediated signal is sufficient to explain the
      inhibitory effect of CTLA4.

PMID- 9653098
TI  - Nuclear factor (NF)-kappaB-regulated X-chromosome-linked iap gene expression
      protects endothelial cells from tumor necrosis factor alpha-induced apoptosis.
AB  - By differential screening of tumor necrosis factor alpha (TNF-alpha) and
      lipopolysaccharide (LPS)- activated endothelial cells (ECs), we have identified a
      cDNA clone that turned out to be a member of the inhibitor of apoptosis (iap)
      gene family. iap genes function to protect cells from undergoing apoptotic death
      in response to a variety of stimuli. These iap genes, hiap1, hiap2, and xiap were
      found to be strongly upregulated upon treatment of ECs with the inflammatory
      cytokines TNF-alpha, interleukin 1beta, and LPS, reagents that lead to activation
      of the nuclear transcription factor kappaB (NF-kappaB). Indeed, overexpression of
      IkappaBalpha, an inhibitor of NF-kappaB, suppresses the induced expression of iap
      genes and sensitizes ECs to TNF-alpha-induced apoptosis. Ectopic expression of
      one member of the human iap genes, human X-chromosome-linked iap (xiap), using
      recombinant adenovirus overrules the IkappaBalpha effect and protects ECs from
      TNF-alpha- induced apoptosis. We conclude that xiap represents one of the NF
      kappaB-regulated genes that counteracts the apoptotic signals caused by TNF-alpha
      and thereby prevents ECs from undergoing apoptosis during inflammation.

PMID- 9653099
TI  - Reversal of proinflammatory responses by ligating the macrophage Fcgamma receptor
      type I.
AB  - Macrophages can respond to a variety of infectious and/or inflammatory stimuli by
      secreting an array of proinflammatory cytokines, the overproduction of which can
      result in shock or even death. In this report, we demonstrate that ligation of
      macrophage Fcgamma receptors (FcgammaR) can lead to a reversal of macrophage
      proinflammatory responses by inducing an upregulation of interleukin (IL)-10,
      with a reciprocal inhibition of IL-12 production. IL-10 upregulation was specific
      to FcgammaR ligation, since the ligation of the Mac-1 receptor did not alter IL
      10 production. The identification of the specific FcgammaR subtype responsible
      for IL-10 upregulation was determined in gene knockout mice. Macrophages from
      mice lacking the FcR gamma chain, which is required for assembly and signaling by
      FcgammaRI and FcgammaRIII, failed to upregulate IL-10 in response to immune
      complexes. However, mice lacking either the FcgammaRII or the FcgammaRIII were
      fully capable of upregulating IL-10 production, implicating FcgammaRI in this
      process. The biological consequences of FcgammaRI ligation were determined in
      both in vitro and in vivo models of inflammation and sepsis. In all of the models
      tested, the ligation of FcgammaR promoted the production of IL-10 and inhibited
      the secretion of IL-12. This reciprocal alteration in the pattern of macrophage
      cytokine production illustrates a potentially important role for FcgammaR
      mediated clearance in suppressing macrophage proinflammatory responses.

PMID- 9653100
TI  - Chloride channels and endocytosis: ClC-5 makes a dent.

PMID- 9653101
TI  - An infectious origin of extraskeletal calcification.

PMID- 9653102
TI  - A new twist on protein crystallization.

PMID- 9653103
TI  - The instability of stratified flows at large Richardson numbers.
AB  - In contrast to conventional expectations based on the stability of steady shear
      flows, elementary time-periodic stratified flows that are unstable at arbitrarily
      large Richardson numbers are presented here. The fundamental instability is a
      parametric one with twice the period of the basic state. This instability
      spontaneously generates local shears on buoyancy time scales near a specific
      angle of inclination that saturates into a localized regime of strong mixing with
      density overturning. We speculate that such instabilities may contribute
      significantly to the step-like microstructure often observed in buoyancy
      measurements in the ocean.

PMID- 9653104
TI  - Stable relativistic/charge-displacement channels in ultrahigh power density
      (approximately 10(21 W/cm3) plasmas.
AB  - Robust stability is a chief characteristic of relativistic/charge-displacement
      self-channeling. Theoretical analysis of the dynamics of this stability (i)
      reveals a leading role for the eigenmodes in the development of stable channels,
      (ii) suggests a technique using a simple longitudinal gradient in the electron
      density to extend the zone of stability into the high electron density/high power
      density regime, (iii) indicates that a situation approaching unconditional
      stability can be achieved, (iv) demonstrates the efficacy of the stable dynamics
      in trapping severely perturbed beams in single uniform channels, and (v) predicts
      that approximately 10(4) critical powers can be trapped in a single stable
      channel. The scaling of the maximum power density with the propagating wavelength
      lambda is shown to be proportional to lambda-4 for a given propagating power and
      a fixed ratio of the electron plasma density to the critical plasma density. An
      estimate of the maximum power density that can be achieved in these channels with
      a power of approximately 2 TW at a UV (248 nm) wavelength gives a value of
      approximately 10(21) W/cm3 with a corresponding atomic specific magnitude of
      approximately 60 W/atom. The characteristic intensity propagating in the channel
      under these conditions exceeds 10(21) W/cm2.

PMID- 9653105
TI  - Genes from mycoparasitic fungi as a source for improving plant resistance to
      fungal pathogens.
AB  - Disease resistance in transgenic plants has been improved, for the first time, by
      the insertion of a gene from a biocontrol fungus. The gene encoding a strongly
      antifungal endochitinase from the mycoparasitic fungus Trichoderma harzianum was
      transferred to tobacco and potato. High expression levels of the fungal gene were
      obtained in different plant tissues, which had no visible effect on plant growth
      and development. Substantial differences in endochitinase activity were detected
      among transformants. Selected transgenic lines were highly tolerant or completely
      resistant to the foliar pathogens Alternaria alternata, A. solani, Botrytis
      cinerea, and the soilborne pathogen Rhizoctonia solani. The high level and the
      broad spectrum of resistance obtained with a single chitinase gene from
      Trichoderma overcome the limited efficacy of transgenic expression in plants of
      chitinase genes from plants and bacteria. These results demonstrate a rich source
      of genes from biocontrol fungi that can be used to control diseases in plants.

PMID- 9653106
TI  - An adenoviral vector deleted for all viral coding sequences results in enhanced
      safety and extended expression of a leptin transgene.
AB  - Adenoviral (Ad)-mediated in vivo gene transfer and expression are limited in part
      by cellular immune responses to viral-encoded proteins and/or transgene
      immunogenicity. In an attempt to diminish the former responses, we have
      previously developed and described helper-dependent (HD) Ad vectors in which the
      viral protein coding sequences are completely eliminated. These HD vectors have
      up to 37 kb insert capacity, are easily propagated in a Cre recombinase-based
      system, and can be produced to high concentration and purity (>99.9% helper-free
      vector). In this study, we compared safety and efficacy of leptin gene delivery
      mediated by an HD vector (HD-leptin) and a first-generation E1-deleted Ad vector
      (Ad-leptin) in normal lean and ob/ob (leptin-deficient) mice. In contrast to
      evidence of liver toxicity, inflammation, and cellular infiltration observed with
      Ad-leptin delivery in mice, HD-leptin delivery was associated with a significant
      improvement in associated safety/toxicity and resulted in efficient gene
      delivery, prolonged elevation of serum leptin levels, and associated weight loss.
      The greater safety, efficient gene delivery, and increased insert capacity of HD
      vectors are significant improvements over current Ad vectors and represent
      favorable features especially for clinical gene therapy applications.

PMID- 9653107
TI  - Lower intracellular hydrogen peroxide levels in cells overexpressing CuZn
      superoxide dismutase.
AB  - Transfection of V79 Chinese hamster cells produced clones in which CuZn
      superoxide dismutase (CuZn-SOD) activities were 2.2- to 3. 5-fold higher than in
      the parental cells. An overall reduction of antioxidant enzyme activities and
      both total and oxidized glutathione levels had been found in these clones.
      Aconitase activities in these cells were determined to indirectly measure the O2-
      steady-state levels. As expected, in cells overexpressing CuZn-SOD, both total
      and cytosolic aconitase activities have increased. Because these clones showed
      reduced oxidized glutathione contents, it is unlikely that they present higher
      H2O2 steady-state levels as a consequence of the higher SOD levels. This was
      confirmed by measuring H2O2 steady-state levels in cells by flow cytometric
      analysis of 2',7'-dichlorofluorescein diacetate-treated cells. Despite the
      decreased antioxidant defenses, three of the clones overexpressing CuZn-SOD
      showed reduced H2O2 steady-state levels. These reduced H2O2 steady-state levels
      were found even when the cells were treated with the O2- generator 2,3-dimethoxy
      1, 4-naphthoquinone. These data provide in vivo support for the hypothesis
      proposed by Liochev and Fridovich [Liochev, S. I. & Fridovich, I. (1994) Free
      Radical Biol. Med. 16, 29-33] that O2- dismutation prevents the formation of
      higher H2O2 levels by other reactions.

PMID- 9653108
TI  - Structural similarities between topoisomerases that cleave one or both DNA
      strands.
AB  - Type IA and type II DNA topoisomerases are distinguished by their ability to
      cleave one or two strands, respectively, of a DNA duplex. Both types have been
      proposed to use an "enzyme-bridging" mechanism, in which a break is formed in a
      DNA strand and a gap is opened between the broken pieces to allow passage of a
      second DNA strand or duplex segment. Although the type IA and type II
      topoisomerase structures appear overall quite different from one another,
      unexpected similarities between several structural elements suggest that members
      of the two subfamilies may use comparable mechanisms to bind and cleave DNA.

PMID- 9653109
TI  - Control of interferon-tau gene expression by Ets-2.
AB  - Expression of the multiple interferon-tau (IFN-tau) genes is restricted to
      embryonic trophectoderm of ruminant ungulate species for a few days in early
      pregnancy. The promoter regions of these genes are highly conserved. A proximal
      (bp -91 to -69) sequence has been implicated in controlling trophoblast-specific
      expression. Here it was used as a target for yeast one-hybrid screening of a day
      13 conceptus cDNA library. Two transcription factors of the Ets family, Ets-2 and
      GABPalpha, were identified, consistent with the observation that active ovine IFN
      tau genes contain a single 10-bp Ets motif (core: GGAA) in the proximal segment,
      whereas three known inactive ovine genes contain a mutated core motif (TGAA).
      Cotransfection of a promoter- (-126 to +50) luciferase reporter construct from an
      active gene (bovineIFN-tau1; boIFNT1) and an Ets-2 expression plasmid in human
      JAr cells provided up to a 30-fold increase in reporter expression, whereas
      promoters from inactive genes were not transactivated. GABPalpha alone was
      ineffective and had only a approximately 2-fold positive effect when coexpressed
      with its partner GABPbeta. Other Ets-related transcription factors, which were
      not detected in the genetic screen, also provided a range of lesser
      transactivation effects. Coexpression of Ets-2 and activated Ras failed to
      transactivate the IFNT promoter greater than Ets-2 alone in JAr cells. The
      presence of Ets-2 in nuclei of embryonic trophectoderm was confirmed
      immunocytochemically. Together, these data suggest that Ets-2 plays a role in the
      transient expression of the nonvirally inducible IFNT genes.

PMID- 9653110
TI  - Mammalian Golgi apparatus UDP-N-acetylglucosamine transporter: molecular cloning
      by phenotypic correction of a yeast mutant.
AB  - Transporters in the Golgi apparatus membrane translocate nucleotide sugars from
      the cytosol into the Golgi lumen before these can be substrates for the
      glycosylation of proteins, lipids, and proteoglycans. We have cloned the
      mammalian Golgi membrane transporter for uridine diphosphate-N-acetylglucosamine
      by phenotypic correction with cDNA from MDCK cells of a recently characterized
      Kluyveromyces lactis mutant deficient in Golgi transport of the above nucleotide
      sugar. Phenotypically corrected transformants were separated from mutants in a
      fluorescent-activated cell sorter after labeling of K. lactis cells with
      fluorescein isothiocyanate (FITC) conjugated to Griffonia simplicifolia II
      lectin, which binds terminal N-acetylglucosamine. A 2-kb DNA fragment was found
      to restore the wild-type cell lectin binding phenotype, which reverted to the
      mutant one upon loss of the plasmid. The DNA fragment contained an ORF encoding a
      hydrophobic, multitransmembrane spanning protein of 326 aa that had only 22%
      amino acid sequence identity with the corresponding transporter from K. lactis
      but showed 53% amino acid sequence identity to the mammalian UDP-galactose
      transporters and 40% to the CMP-sialic acid transporter. Golgi vesicles from the
      transformant regained their ability to transport UDP-GlcNAc in an assay in vitro.
      The above results demonstrate that the mammalian Golgi UDP-GlcNAc transporter
      gene has all of the necessary information for the protein to be expressed and
      targeted functionally to the Golgi apparatus of yeast and that two proteins with
      very different amino acid sequences may transport the same solute within the same
      Golgi membrane.

PMID- 9653111
TI  - Structural, functional, and evolutionary relationships between lambda-exonuclease
      and the type II restriction endonucleases.
AB  - lambda-exonuclease participates in DNA recombination and repair. It binds a free
      end of double-stranded DNA and degrades one strand in the 5' to 3' direction. The
      primary sequence does not appear to be related to any other protein, but the
      crystal structure shows part of lambda-exonuclease to be similar to the type II
      restriction endonucleases PvuII and EcoRV. There is also a weaker correspondence
      with EcoRI, BamHI, and Cfr10I. The structure comparisons not only suggest that
      these enzymes all share a similar catalytic mechanism and a common structural
      ancestor but also provide strong evidence that the toroidal structure of lambda
      exonuclease encircles its DNA substrate during hydrolysis.

PMID- 9653112
TI  - The mouse and human genes encoding the recognition component of the N-end rule
      pathway.
AB  - The N-end rule relates the in vivo half-life of a protein to the identity of its
      N-terminal residue. The N-end rule pathway is one proteolytic pathway of the
      ubiquitin system. The recognition component of this pathway, called N-recognin or
      E3, binds to a destabilizing N-terminal residue of a substrate protein and
      participates in the formation of a substrate-linked multiubiquitin chain. We
      report the cloning of the mouse and human Ubr1 cDNAs and genes that encode a
      mammalian N-recognin called E3alpha. Mouse UBR1p (E3alpha) is a 1,757-residue
      (200-kDa) protein that contains regions of sequence similarity to the 225-kDa
      Ubr1p of the yeast Saccharomyces cerevisiae. Mouse and human UBR1p have apparent
      homologs in other eukaryotes as well, thus defining a distinct family of
      proteins, the UBR family. The residues essential for substrate recognition by the
      yeast Ubr1p are conserved in the mouse UBR1p. The regions of similarity among the
      UBR family members include a putative zinc finger and RING-H2 finger, another
      zinc-binding domain. Ubr1 is located in the middle of mouse chromosome 2 and in
      the syntenic 15q15-q21.1 region of human chromosome 15. Mouse Ubr1 spans
      approximately 120 kilobases of genomic DNA and contains approximately 50 exons.
      Ubr1 is ubiquitously expressed in adults, with skeletal muscle and heart being
      the sites of highest expression. In mouse embryos, the Ubr1 expression is highest
      in the branchial arches and in the tail and limb buds. The cloning of Ubr1 makes
      possible the construction of Ubr1-lacking mouse strains, a prerequisite for the
      functional understanding of the mammalian N-end rule pathway.

PMID- 9653113
TI  - PRT1 of Arabidopsis thaliana encodes a component of the plant N-end rule pathway.
AB  - Mutants in the PRT1 gene of Arabidopsis thaliana are impaired in the degradation
      of a normally short-lived intracellular protein that contains a destabilizing N
      terminal residue. Proteins bearing such residues are the substrates of an
      ubiquitin-dependent proteolytic system called the N-end rule pathway. The
      chromosomal position of PRT1 was determined, and the PRT1 gene was isolated by
      map-based cloning. The 45-kDa PRT1 protein contains two RING finger domains and
      one ZZ domain. No other proteins in databases match these characteristics of
      PRT1. There is, however, a weak similarity to Rad18p of Saccharomyces cerevisiae.
      The RING finger domains have been found in a number of other proteins that are
      involved in ubiquitin conjugation, consistent with the proposed role of PRT1 in
      the plant N-end rule pathway.

PMID- 9653114
TI  - Solution structure of the cytohesin-1 (B2-1) Sec7 domain and its interaction with
      the GTPase ADP ribosylation factor 1.
AB  - Cytohesin-1 (B2-1) is a guanine nucleotide exchange factor for human ADP
      ribosylation factor (Arf) GTPases, which are important for vesicular protein
      trafficking and coatamer assembly in the cell. Cytohesin-1 also has been reported
      to promote cellular adhesion via binding to the beta2 integrin cytoplasmic
      domain. The solution structure of the Sec7 domain of cytohesin-1, which is
      responsible for both the protein's guanine nucleotide exchange factor function
      and beta2 integrin binding, was determined by NMR spectroscopy. The structure
      consists of 10 alpha-helices that form a unique tertiary fold. The binding
      between the Sec7 domain and a soluble, truncated version of human Arf-1 was
      investigated by examining 1H-15N and 1H-13C chemical shift changes between the
      native protein and the Sec7/Arf-1 complex. We show that the binding to Arf-1
      occurs through a large surface on the C-terminal subdomain that is composed of
      both hydrophobic and polar residues. Structure-based mutational analysis of the
      cytohesin-1 Sec7 domain has been used to identify residues important for binding
      to Arf and for mediating nucleotide exchange. Investigations into the interaction
      between the Sec7 domain and the beta2 integrin cytoplasmic domain suggest that
      the two proteins do not interact in the solution phase.

PMID- 9653116
TI  - Arabinogalactan-proteins from Nicotiana alata and Pyrus communis contain
      glycosylphosphatidylinositol membrane anchors.
AB  - Arabinogalactan-proteins (AGPs) are a class of proteoglycans found in cell
      secretions and plasma membranes of plants. Attention is currently focused on
      their structure and their potential role in growth and development. We present
      evidence that two members of a major class of AGPs, the classical AGPs, AGPNa1
      from styles of Nicotiana alata and AGPPc1 from cell suspension cultures of Pyrus
      communis, undergo C-terminal processing involving glycosylphosphatidylinositol
      membrane anchors. The evidence is that (i) the transmembrane helix at the C
      terminus predicted from the cDNA encoding these proteins is not present-the C
      terminal amino acid is Asn87 and Ser97 for AGPNa1 and AGPPc1, respectively; (ii)
      both AGP protein backbones are substituted with ethanolamine at the C-terminal
      amino acid; and (iii) inositol, glucosamine, and mannose are present in the
      native AGPs. An examination of the deduced amino acid sequences of other
      classical AGP protein backbones shows that glycosylphosphatidylinositol-anchors
      may be a common feature of this class of AGPs.

PMID- 9653115
TI  - Molecular basis of cooperative DNA bending and oriented heterodimer binding in
      the NFAT1-Fos-Jun-ARRE2 complex.
AB  - Cooperative DNA binding by transcription factors that bind to separate
      recognition sites is likely to require bending of intervening sequences and the
      appropriate orientation of transcription factor binding. We investigated DNA
      bending in complexes formed by the basic region-leucine zipper domains of Fos and
      Jun with the DNA binding region of nuclear factor of activated T cells 1 (NFAT1)
      at composite regulatory elements using gel electrophoretic phasing analysis. The
      NFAT1-Fos-Jun complex induced a bend at the ARRE2 site that was distinct from the
      sum of the bends induced by NFAT1 and Fos-Jun separately. We designate this
      difference DNA bending cooperativity. The bending cooperativity was directed
      toward the interaction interface between Fos-Jun and NFAT1. We also examined the
      influence of NFAT1 on the orientation of Fos-Jun heterodimer binding using a
      novel fluorescence resonance energy transfer assay. The interaction with NFAT1
      could reverse the orientation of Fos-Jun heterodimer binding to the ARRE2 site.
      The principal determinants of both cooperative DNA bending and oriented
      heterodimer binding were localized to three amino acid residues at the amino
      terminal ends of the leucine zippers of Fos and Jun. Consequently, interactions
      between transcription factors can remodel promoters by altering DNA bending and
      the orientation of heterodimer binding.

PMID- 9653117
TI  - The tyrosine kinase regulator Cbl enhances the ubiquitination and degradation of
      the platelet-derived growth factor receptor alpha.
AB  - The Cbl protooncogene product has emerged as a negative regulator of receptor and
      nonreceptor tyrosine kinases. We recently demonstrated that oncogenic Cbl mutants
      upregulate the endogenous tyrosine kinase signaling machinery when expressed in
      the NIH 3T3 cells, and identified the platelet-derived growth factor receptor
      alpha (PDGFRalpha) as one of the tyrosine kinases targeted by these oncogenes.
      These findings suggested a role for the normal Cbl protein in negative regulation
      of the PDGFRalpha. However, the mechanism of such negative regulation remained to
      be determined. Here we show that overexpression of the wild-type Cbl enhances the
      ligand-induced ubiquitination of the PDGFRalpha. Concomitantly, the PDGFRalpha in
      Cbl-overexpressing cells undergoes a faster ligand-induced degradation compared
      with that in the control cells. These results identify a role for Cbl in the
      regulation of ligand-induced ubiquitination and degradation of receptor tyrosine
      kinases and suggest one potential mechanism for evolutionarily conserved negative
      regulatory influence of Cbl on tyrosine kinases.

PMID- 9653118
TI  - The stability of the RNA bases: implications for the origin of life.
AB  - High-temperature origin-of-life theories require that the components of the first
      genetic material are stable. We therefore have measured the half-lives for the
      decomposition of the nucleobases. They have been found to be short on the
      geologic time scale. At 100 degreesC, the growth temperatures of the
      hyperthermophiles, the half-lives are too short to allow for the adequate
      accumulation of these compounds (t1/2 for A and G approximately 1 yr; U = 12 yr;
      C = 19 days). Therefore, unless the origin of life took place extremely rapidly
      (<100 yr), we conclude that a high-temperature origin of life may be possible,
      but it cannot involve adenine, uracil, guanine, or cytosine. The rates of
      hydrolysis at 100 degreesC also suggest that an ocean-boiling asteroid impact
      would reset the prebiotic clock, requiring prebiotic synthetic processes to begin
      again. At 0 degreesC, A, U, G, and T appear to be sufficiently stable (t1/2 >/=
      10(6) yr) to be involved in a low-temperature origin of life. However, the lack
      of stability of cytosine at 0 degreesC (t1/2 = 17, 000 yr) raises the possibility
      that the GC base pair may not have been used in the first genetic material unless
      life arose quickly (<10(6) yr) after a sterilization event. A two-letter code or
      an alternative base pair may have been used instead.

PMID- 9653119
TI  - The TRAP220 component of a thyroid hormone receptor- associated protein (TRAP)
      coactivator complex interacts directly with nuclear receptors in a ligand
      dependent fashion.
AB  - Cognate cDNAs are described for 2 of the 10 thyroid hormone receptor-associated
      proteins (TRAPs) that are immunopurified with thyroid hormone receptor alpha
      (TRalpha) from ligand-treated HeLa (alpha-2) cells. Both TRAP220 and TRAP100
      contain LXXLL domains found in other nuclear receptor-interacting proteins and
      both appear to reside in a single complex with other TRAPs (in the absence of
      TR). However, only TRAP220 shows a direct ligand-dependent interaction with
      TRalpha, and these interactions are mediated through the C terminus of TRalpha
      and (at least in part) the LXXLL domains of TRAP220. TRAP220 also interacts with
      other nuclear receptors [vitamin D receptor, retinoic acid receptor alpha,
      retinoid X receptor alpha, peroxisome proliferation-activated receptor (PPAR)
      alpha, PPARgamma and, to a lesser extent, estrogen receptor] in a ligand
      dependent manner, whereas TRAP100 shows only marginal interactions with estrogen
      receptor, retinoid X receptor alpha, PPARalpha, and PPARgamma. Consistent with
      these results, TRAP220 moderately stimulates human TRalpha-mediated transcription
      in transfected cells, whereas a fragment containing the LXXLL motifs acts as a
      dominant negative inhibitor of nuclear receptor-mediated transcription both in
      transfected cells (TRalpha) and in cell free transcription systems (TRalpha and
      vitamin D receptor). These studies indicate that TRAP220 plays a major role in
      anchoring other TRAPs to TRalpha during the function of the TRalpha-TRAP complex
      and, further, that TRAP220 (possibly along with other TRAPs) may be a global
      coactivator for the nuclear receptor superfamily.

PMID- 9653120
TI  - Activity of the yeast MNN1 alpha-1,3-mannosyltransferase requires a motif
      conserved in many other families of glycosyltransferases.
AB  - A wide diversity of biological molecules are modified by the addition of sugar
      residues, and a large number of glycosyltransferases have been identified that
      are responsible for these reactions. Despite catalyzing closely related
      reactions, many of these transferases show little apparent sequence homology. By
      comparing two apparently unrelated families of yeast Golgi mannosyltransferases,
      a short motif containing two aspartate residues was observed that was conserved
      in both groups of proteins. Mutagenesis of one of the members of these families,
      the alpha-1, 3-mannosyltransferase Mnn1p, showed that altering either of these
      aspartates eliminates all enzymatic activity. These changes do not appear to
      affect the overall folding and assembly of Mnn1p. A similar aspartate-containing
      sequence was found to be conserved in a diverse range of other
      glycosyltransferase families, much more frequently than would be expected by
      chance, suggesting that it is a feature of the catalytic site, or an element of a
      structural fold, shared by many glycosyltransferases.

PMID- 9653121
TI  - Functional coupling between secretory phospholipase A2 and cyclooxygenase-2 and
      its regulation by cytosolic group IV phospholipase A2.
AB  - Secretory phospholipase A2 (sPLA2) is the major effector involved in arachidonic
      acid (AA) mobilization and prostaglandin E2 (PGE2) production during stimulation
      of P388D1 macrophages with the inflammatory stimuli bacterial lipopolysaccharide
      and platelet-activating factor. We herein demonstrate that PGE2 in stimulated
      P388D1 cells is accounted for by the inducible cyclooxygenase (COX)-2. COX-1,
      though present, appears not to participate significantly in stimulus-induced PGE2
      production in P388D1 macrophages. Reconstitution experiments utilizing exogenous
      recombinant sPLA2 demonstrate that activation of the sPLA2 at the plasma membrane
      is highly dependent on previous activation of the cytosolic phospholipase A2
      (cPLA2). Collectively these results demonstrate (i) that functional coupling
      exists between sPLA2 and COX-2 in activated cells, (ii) the critical role that
      cPLA2 plays in lipid mediator production, and (iii) that there is crosstalk
      between cPLA2 and sPLA2 in the cell.

PMID- 9653122
TI  - An N-terminal fragment of the gene 4 helicase/primase of bacteriophage T7 retains
      primase activity in the absence of helicase activity.
AB  - Primase and helicase activities of bacteriophage T7 are present in a single
      polypeptide coded by gene 4. Because the amino terminal region of the gene 4
      protein contributes to primase activity, we constructed a truncated gene 4
      encoding the N-terminal 271-aa residues. The truncated protein, purified from
      cells overexpressing the protein, is a dimer in solution; the full-length protein
      is a hexamer. Although the fragment is devoid of dTTPase and helicase activities,
      it catalyzes template-directed synthesis of di-, tri-, and tetranucleotides. The
      rates for tetraribonucleotide synthesis and for dinucleotide extension on a 20
      nucleotide template are similar for the full-length and truncated proteins.
      However, the activity of the primase fragment is unaffected by dTTP whereas the
      primase activity of the full-length protein is stimulated >14-fold. The primase
      fragment is defective in the interaction with T7 DNA polymerase in that primer
      synthesis cannot be coupled to DNA synthesis.

PMID- 9653123
TI  - Functional and molecular characterization of a glycosomal PPi-dependent enzyme in
      trypanosomatids: pyruvate, phosphate dikinase.
AB  - Trypanosomatids are parasitic protists that have an ATP-dependent glycolysis with
      no indication of PPi-dependent metabolism. Most of the glycolysis takes place in
      peroxisome-like organelles, the glycosomes. We characterized in Trypanosoma
      brucei a single-copy gene encoding a PPi-dependent enzyme, pyruvate, phosphate
      dikinase (PPDK), which was expressed functionally in Escherichia coli. Specific
      antibodies detected a 100-kDa protein in procyclic forms but not in mammalian
      forms of T. brucei, indicating a differential expression. Glycosomal localization
      of PPDK was determined by immunofluorescence analysis and was confirmed by
      Western blot analysis on glycosomal fractions by using anti-PPDK antibodies.
      Expression and localization of recombinant PPDKs in procyclic forms of T. brucei
      showed that the AKL motif at the C-terminal extremity of PPDK is necessary for
      glycosomal targeting. PPDK was detected in every trypanosomatid tested
      Trypanosoma congolense, Trypanosoma vivax, Trypanosoma cruzi, Phytomonas,
      Crithidia and Leishmania-with a good correlation between amount of protein and
      enzymatic activity. The precise role of PPDK in trypanosomatid carbohydrate
      metabolism remains to be clarified.

PMID- 9653124
TI  - The SbcCD nuclease of Escherichia coli is a structural maintenance of chromosomes
      (SMC) family protein that cleaves hairpin DNA.
AB  - Hairpin structures can inhibit DNA replication and are intermediates in certain
      recombination reactions. We have shown that the purified SbcCD protein of
      Escherichia coli cleaves a DNA hairpin. This cleavage does not require the
      presence of a free (3' or 5') DNA end and generates products with 3'-hydroxyl and
      5'-phosphate termini. Electron microscopy of SbcCD has revealed the "head-rod
      tail" structure predicted for the SMC (structural maintenance of chromosomes)
      family of proteins, of which SbcC is a member. This work provides evidence
      consistent with the proposal that SbcCD cleaves hairpin structures that halt the
      progress of the replication fork, allowing homologous recombination to restore
      DNA replication.

PMID- 9653125
TI  - Structural characterization and immunochemical detection of a fluorophore derived
      from 4-hydroxy-2-nonenal and lysine.
AB  - Aging and the progression of certain degenerative diseases are accompanied by
      increases in intracellular fluorescent material, termed "lipofuscin" and ceroid,
      respectively. These pigments are observed within granules composed, in part, of
      damaged protein and lipid. Modification of various biomolecules by aldehyde
      products of lipid peroxidation is believed to contribute to lipofuscin and ceroid
      formation. However, little direct evidence currently exists because the
      structures responsible for the fluorescent, cross-linked nature of this material
      are not well characterized. In this study, we have identified a fluorescent
      product formed in the reaction of Nalpha-acetyllysine and 4-hydroxy-2-nonenal
      (HNE), a major product of lipid peroxidation and the most reactive of these
      compounds under physiological conditions [Esterbauer, H., Shaur, R. J. & Zollner,
      H. (1991) Free Radical Biol. Med. 11, 81-128]. This fluorescent compound,
      characterized as a 2-hydroxy-3-imino-1,2-dihydropyrrol derivative, appears to
      form upon oxidative cyclization of the nonfluorescent 2:1 lysine-HNE Michael
      adduct-Schiff base cross-link. Polyclonal antibody was raised to the Nalpha
      acetyllysine-HNE fluorophore and found to be highly specific to the chromophore
      structure of the compound. This antibody has been used to conclusively
      demonstrate that the lysine-HNE derivative of this fluorophore forms on protein
      upon exposure to HNE. The results of this study therefore provide the basis for
      future investigations on the contribution(s) of HNE-derived fluorophore formation
      to lipofuscin and ceroid accumulation.

PMID- 9653126
TI  - Localization of signal recognition particle RNA in the nucleolus of mammalian
      cells.
AB  - The signal recognition particle (SRP) of eukaryotic cells is a cytoplasmic
      ribonucleoprotein machine that arrests the translational elongation of nascent
      secretory and membrane proteins and facilitates their transport into the
      endoplasmic reticulum. The spatial pathway of SRP RNA processing and
      ribonucleoprotein assembly in the cell is not known. In the present
      investigation, microinjection of fluorescently tagged SRP RNA into the nucleus of
      mammalian cells was used to examine its intranuclear sites of localization.
      Microinjection of SRP RNA into the nuclei of normal rat kidney (NRK) epithelial
      cells maintained at 37 degreesC on the microscope stage resulted in a very rapid
      initial localization in nucleoli, followed by a progressive decline of nucleolar
      signal and an increase of fluorescence at discrete sites in the cytoplasm.
      Nuclear microinjection of a molecule corresponding to a major portion of the Alu
      domain of SRP RNA revealed a pattern of rapid nucleolar localization followed by
      cytoplasmic appearance of signal that was similar to the results obtained with
      full-length SRP RNA. In contrast, a molecule corresponding to the S domain of SRP
      RNA did not display nucleolar localization to the extent observed with full
      length SRP RNA. An SRP RNA molecule lacking helix 6 of the S domain displayed
      normal nucleolar localization, whereas one lacking helix 8 of the S domain did
      not. These results, obtained by direct, real-time observation of fluorescent RNA
      molecules inside the nucleus of living mammalian cells, suggest that the
      processing of SRP RNA or its ribonucleoprotein assembly into the SRP involves a
      nucleolar phase.

PMID- 9653127
TI  - Regulation of hypoxia-inducible factor 1alpha is mediated by an O2-dependent
      degradation domain via the ubiquitin-proteasome pathway.
AB  - Hypoxia induces a group of physiologically important genes such as erythropoietin
      and vascular endothelial growth factor. These genes are transcriptionally up
      regulated by hypoxia-inducible factor 1 (HIF-1), a global regulator that belongs
      to the basic helix-loop-helix PAS family. Although HIF-1 is a heterodimer
      composed of alpha and beta subunits, its activity is primarily determined by
      hypoxia-induced stabilization of HIF-1alpha, which is otherwise rapidly degraded
      in oxygenated cells. We report the identification of an oxygen-dependent
      degradation (ODD) domain within HIF-1alpha that controls its degradation by the
      ubiquitin-proteasome pathway. The ODD domain consists of approximately 200 amino
      acid residues, located in the central region of HIF-1alpha. Because portions of
      the domain independently confer degradation of HIF-1alpha, deletion of this
      entire region is required to give rise to a stable HIF-1alpha, capable of
      heterodimerization, DNA-binding, and transactivation in the absence of hypoxic
      signaling. Conversely, the ODD domain alone confers oxygen-dependent instability
      when fused to a stable protein, Gal4. Hence, the ODD domain plays a pivotal role
      for regulating HIF-1 activity and thereby may provide a means of controlling gene
      expression by changes in oxygen tension.

PMID- 9653128
TI  - Gp91(phox) is the heme binding subunit of the superoxide-generating NADPH
      oxidase.
AB  - The phagocyte NADPH oxidase flavocytochrome b558 is a membrane-bound heterodimer
      comprised of a glycosylated subunit, gp91(phox), and a nonglycosylated subunit,
      p22(phox). It contains two nonidentical heme groups that mediate the final steps
      of electron transfer to molecular oxygen (O2), resulting in the generation of
      superoxide ion (O2-). However, the location of the hemes within the
      flavocytochrome heterodimer remains controversial. In this study, we have used
      transgenic COS7 cell lines expressing gp91(phox), p22(phox), or both polypeptides
      to examine the relative role of each flavocytochrome b558 subunit in heme binding
      and O2- formation. A similar membrane localization was observed when gp91(phox)
      and p22(phox) were either expressed individually or coexpressed, as analyzed by
      confocal microscopy and immunoblotting of subcellular fractions. Spectral
      analysis of membranes prepared from COS7 cell lines expressing either gp91(phox)
      or both gp91(phox) and p22(phox) showed a b-type cytochrome with spectral
      characteristics identical to those of human neutrophil flavocytochrome b558. In
      contrast, no heme spectrum was detected in wild-type COS7 membranes or those
      containing only p22(phox). Furthermore, redox titration studies suggested that
      two heme groups were contained in gp91(phox) expressed in COS7 membranes, with
      midpoint potentials of -264 and -233 mV that were very similar to those obtained
      for neutrophil flavocytochrome b558. These results provide strong support for the
      hypothesis that gp91(phox) is the sole heme binding subunit of flavocytochrome
      b558. However, coexpression of gp91(phox) and p22(phox) in COS7 membranes was
      required to support O2- production in combination with neutrophil cytosol,
      indicating that the functional assembly of the active NADPH oxidase complex
      requires both subunits of flavocytochrome b558.

PMID- 9653129
TI  - High level transactivation by a modified Bombyx ecdysone receptor in mammalian
      cells without exogenous retinoid X receptor.
AB  - Our studies of the Bombyx mori ecdysone receptor (BE) revealed that, unlike the
      Drosophila melanogaster ecdysone receptor (DE), treatment of BE with the ecdysone
      agonist tebufenozide stimulated high level transactivation in mammalian cells
      without adding an exogenous heterodimer partner. Gel mobility shift and
      transfection assays with both the ultraspiracle gene product (Usp) and retinoid X
      receptor heterodimer partners indicated that this property of BE stems from
      significantly augmented heterodimer complex formation and concomitant DNA
      binding. We have mapped this "gain of function" to determinants within the D and
      E domains of BE and demonstrated that, although the D domain determinant is
      sufficient for high affinity heterodimerization with Usp, both determinants are
      necessary for high affinity interaction with retinoid X receptor. Modified BE
      receptors alone used as replication-defective retroviruses potently stimulated
      separate "reporter" viruses in all cell types examined, suggesting that BE has
      potentially broad utility in the modulation of transgene expression in mammalian
      cells.

PMID- 9653130
TI  - gp120 envelope glycoproteins of human immunodeficiency viruses competitively
      antagonize signaling by coreceptors CXCR4 and CCR5.
AB  - Signal transductions by the dual-function CXCR4 and CCR5 chemokine receptors/HIV
      type 1 (HIV-1) coreceptors were electrophysiologically monitored in Xenopus
      laevis oocytes that also coexpressed the viral receptor CD4 and a G protein
      coupled inward-rectifying K+ channel (Kir 3.1). Large Kir 3.1-dependent currents
      generated in response to the corresponding chemokines (SDF-1alpha for CXCR4 and
      MIP-1alpha; MIP-1beta and RANTES for CCR5) were blocked by pertussis toxin,
      suggesting involvement of inhibitory guanine nucleotide-binding proteins.
      Prolonged exposures to chemokines caused substantial but incomplete
      desensitization of responses with time constants of 5-7 min and recovery time
      constants of 12-19 min. CXCR4 and CCR5 exhibited heterologous desensitization in
      this oocyte system, suggesting possible inhibition of a common downstream step in
      their signaling pathways. In contrast to chemokines, perfusion with monomeric or
      oligomeric preparations of the glycoprotein of Mr 120, 000 (gp120) derived from
      several isolates of HIV-1 did not activate signaling by CXCR4 or CCR5 regardless
      of CD4 coexpression. However, adsorption of the gp120 from a T-cell-tropic virus
      resulted in CD4-dependent antagonism of CXCR4 response to SDF-1alpha, whereas
      gp120 from macrophage-tropic viruses caused CD4-dependent antagonism of CCR5
      response to MIP-1alpha. These antagonisms could be partially overcome by high
      concentrations of chemokines and were specific for coreceptors of the
      corresponding HIV-1 isolates, suggesting that they resulted from direct
      interactions of gp120-CD4 complexes with coreceptors and that they did not
      involve the desensitization pathway. These results indicate that monomeric or
      oligomeric gp120s specifically antagonize CXCR4 and CCR5 signaling in response to
      chemokines, but they do not exclude the possibility that gp120s might also
      function as weak agonists in some cells. The gp120-mediated disruption of CXCR4
      and CCR5 signaling may contribute to AIDS pathogenesis.

PMID- 9653131
TI  - Reaching the global minimum in docking simulations: a Monte Carlo energy
      minimization approach using Bezier splines.
AB  - The docking problem faces two major challenges: the global optimization of a
      multivariable function, such as the energy, and the ability to discriminate
      between true and false positive results, i.e., native from nonnative structures
      based on the input energy function. Among all energy evaluation tools, only a
      local energy-minimization method using an accurate enough potential function is
      able to discriminate between native and nonnative structures. To meet these
      requirements, a Monte Carlo with energy-minimization method has been incorporated
      into a new ECEPP/3 docking program. The efficiency of the simulation results from
      the use of an energy-grid technique based on Bezier splines and from a
      simplification of the receptor by switching on the energy of only important
      residues of the active site. Simulations of a thrombin-inhibitor complex show
      that the global minimum of the energy function was reached in every independent
      run within less than 3 min of time on an IBM RX 6000 computer. For comparison, 10
      standard independent Monte Carlo simulations with 10(6) steps in each were
      carried out. Only three of them led to a conformation close to the x-ray
      structure. The latter simulations required an average of 24 min and about 10 hr
      with and without the grid, respectively. Another important result is that the
      Bezier spline technique not only speeds up the calculation by reducing the number
      of operations during the energy evaluation but also helps in reaching the global
      minimum by smoothing out the potential energy surface.

PMID- 9653132
TI  - Characterizing semilocal motions in proteins by NMR relaxation studies.
AB  - The understanding of protein function is incomplete without the study of protein
      dynamics. NMR spectroscopy is valuable for probing nanosecond and picosecond
      dynamics via relaxation studies. The use of 15N relaxation to study backbone
      dynamics has become virtually standard. Here, we propose to measure the
      relaxation of additional nuclei on each peptide plane allowing for the
      observation of anisotropic local motions. This allows the nature of local motions
      to be characterized in proteins. As an example, semilocal rotational motion was
      detected for part of a helix of the protein Escherichia coli flavodoxin.

PMID- 9653133
TI  - Dioxygen activation and bond cleavage by mixed-valence cytochrome c oxidase.
AB  - Elucidating the structures of intermediates in the reduction of O2 to water by
      cytochrome c oxidase is crucial to understanding both oxygen activation and
      proton pumping by the enzyme. In the work here, the reaction of O2 with the mixed
      valence enzyme, in which only heme a3 and CuB in the binuclear center are
      reduced, has been followed by time-resolved resonance Raman spectroscopy. The
      results show that O==O bond cleavage occurs within the first 200 micros after
      reaction initiation; the presence of a uniquely stable Fe---O---O(H) peroxy
      species is not detected. The product of this rapid reaction is a heme a3
      oxoferryl (FeIV==O) species, which requires that an electron donor in addition to
      heme a3 and CuB must be involved. The available evidence suggests that the
      additional donor is an amino acid side chain. Recent crystallographic data
      [Yoshikawa, S., Shinzawa-Itoh, K., Nakashima, R., Yaono, R., Yamashita, E.,
      Inoue, N., Yao, M., Fei, M. J., Libeu, C. P., Mizushima, T., et al. Science, in
      press; Ostermeier, C., Harrenga, A. , Ermler, U. & Michel, H. (1997) Proc. Natl.
      Acad. Sci. USA 94, 10547-10553] show that one of the CuB ligands, His240, is
      cross-linked to Tyr244 and that this cross-linked tyrosyl is ideally positioned
      to participate in dioxygen activation. We propose a mechanism for O---O bond
      cleavage that proceeds by concerted hydrogen atom transfer from the cross-linked
      His---Tyr species to produce the product oxoferryl species, CuB2+---OH-, and the
      tyrosyl radical. This mechanism provides molecular structures for two key
      intermediates that drive the proton pump in oxidase; moreover, it has clear
      analogies to the proposed O---O bond forming chemistry that occurs during O2
      evolution in photosynthesis.

PMID- 9653134
TI  - Inhibitor binding changes domain mobility in the iron-sulfur protein of the
      mitochondrial bc1 complex from bovine heart.
AB  - We have analyzed crystal structures of cytochrome bc1 complexes with electron
      transfer inhibitors bound to the ubiquinone binding pockets Qi and/or Qo in the
      cytochrome b subunit. The presence or absence of the Qi inhibitor antimycin A did
      not affect the binding of the Qo inhibitors. Different subtypes of Qo inhibitors
      had dramatically different effects on the mobility of the extramembrane domain of
      the iron-sulfur protein (ISP): Binding of 5-undecyl-6-hydroxy-4, 7
      dioxobenzothiazol and stigmatellin (subtype Qo-II and Qo-III, respectively) led
      to a fixation of the ISP domain on the surface of cytochrome b, whereas binding
      of myxothiazol and methoxyacrylate-stilbene (subtype Qo-I) favored release of
      this domain. The native structure has an empty Qo pocket and is intermediate
      between these extremes. On the basis of these observations we propose a model of
      quinone oxidation in the bc1 complex, which incorporates fixed and loose states
      of the ISP as features important for electron transfer and, possibly, also proton
      transport.

PMID- 9653135
TI  - Myosin conformational states determined by single fluorophore polarization.
AB  - Muscle contraction is powered by the interaction of the molecular motor myosin
      with actin. With new techniques for single molecule manipulation and fluorescence
      detection, it is now possible to correlate, within the same molecule and in real
      time, conformational states and mechanical function of myosin. A spot-confocal
      microscope, capable of detecting single fluorophore polarization, was developed
      to measure orientational states in the smooth muscle myosin light chain domain
      during the process of motion generation. Fluorescently labeled turkey gizzard
      smooth muscle myosin was prepared by removal of endogenous regulatory light chain
      and re-addition of the light chain labeled at cysteine-108 with the 6-isomer of
      iodoacetamidotetramethylrhodamine (6-IATR). Single myosin molecule fluorescence
      polarization data, obtained in a motility assay, provide direct evidence that the
      myosin light chain domain adopts at least two orientational states during the
      cyclic interaction of myosin with actin, a randomly disordered state, most likely
      associated with myosin whereas weakly bound to actin, and an ordered state in
      which the light chain domain adopts a finite angular orientation whereas strongly
      bound after the powerstroke.

PMID- 9653136
TI  - Lipid nanotubes as substrates for helical crystallization of macromolecules.
AB  - A general approach for crystallization of proteins in a fast and simple manner
      would be of immense interest to biologists studying protein structure-function
      relationships. Here, we describe a method that we have developed for promoting
      the formation of helical arrays of proteins and macromolecular assemblies.
      Electron micrographs of the arrays are suitable for helical image analysis and
      three-dimensional reconstruction. We show that hydrated mixtures of the
      glycolipid galactosylceramide (GalCer) and derivatized lipids or charged lipids
      form unilamellar nanotubules. The tubules bind proteins in a specific manner via
      high affinity ligands on the polar head groups of the lipid or via electrostatic
      interactions. By doping the GalCer with a novel nickel-containing lipid, we have
      been able to form helical arrays of two histidine-tagged proteins. Similarly,
      doping with a biotinylated lipid allows crystallization of streptavidin. Finally,
      three proteins with affinity for positively or negatively charged lipid layers
      formed helical arrays on appropriately charged tubules. The generality of this
      method may allow a wide variety of proteins to be crystallized on lipid nanotubes
      under physiological conditions.

PMID- 9653137
TI  - Automated high resolution optical mapping using arrayed, fluid-fixed DNA
      molecules.
AB  - New mapping approaches construct ordered restriction maps from fluorescence
      microscope images of individual, endonuclease-digested DNA molecules. In optical
      mapping, molecules are elongated and fixed onto derivatized glass surfaces,
      preserving biochemical accessibility and fragment order after enzymatic
      digestion. Measurements of relative fluorescence intensity and apparent length
      determine the sizes of restriction fragments, enabling ordered map construction
      without electrophoretic analysis. The optical mapping system reported here is
      based on our physical characterization of an effect using fluid flows developed
      within tiny, evaporating droplets to elongate and fix DNA molecules onto
      derivatized surfaces. Such evaporation-driven molecular fixation produces well
      elongated molecules accessible to restriction endonucleases, and notably, DNA
      polymerase I. We then developed the robotic means to grid DNA spots in well
      defined arrays that are digested and analyzed in parallel. To effectively harness
      this effect for high-throughput genome mapping, we developed: (i) machine vision
      and automatic image acquisition techniques to work with fixed, digested molecules
      within gridded samples, and (ii) Bayesian inference approaches that are used to
      analyze machine vision data, automatically producing high-resolution restriction
      maps from images of individual DNA molecules. The aggregate significance of this
      work is the development of an integrated system for mapping small insert clones
      allowing biochemical data obtained from engineered ensembles of individual
      molecules to be automatically accumulated and analyzed for map construction.
      These approaches are sufficiently general for varied biochemical analyses of
      individual molecules using statistically meaningful population sizes.

PMID- 9653138
TI  - Nature of PEVK-titin elasticity in skeletal muscle.
AB  - A unique sequence within the giant titin molecule, the PEVK domain, has been
      suggested to greatly contribute to passive force development of relaxed skeletal
      muscle during stretch. To explore the nature of PEVK elasticity, we used titin
      specific antibodies to stain both ends of the PEVK region in rat psoas myofibrils
      and determined the region's force-extension relation by combining
      immunofluorescence and immunoelectron microscopy with isolated myofibril
      mechanics. We then tried to fit the results with recent models of polymer
      elasticity. The PEVK segment elongated substantially at sarcomere lengths above
      2.4 micro(m) and reached its estimated contour length at approximately 3.5
      micro(m). In immunofluorescently labeled sarcomeres stretched and released
      repeatedly above 3 micro(m), reversible PEVK lengthening could be readily
      visualized. At extensions near the contour length, the average force per titin
      molecule was calculated to be approximately 45 pN. Attempts to fit the force
      extension curve of the PEVK segment with a standard wormlike chain model of
      entropic elasticity were successful only for low to moderate extensions. In
      contrast, the experimental data also could be correctly fitted at high extensions
      with a modified wormlike chain model that incorporates enthalpic elasticity.
      Enthalpic contributions are likely to arise from electrostatic stiffening, as
      evidenced by the ionic-strength dependency of titin-based myofibril stiffness; at
      high stretch, hydrophobic effects also might become relevant. Thus, at
      physiological muscle lengths, the PEVK region does not function as a pure
      entropic spring. Rather, PEVK elasticity may have both entropic and enthalpic
      origins characterizable by a polymer persistence length and a stretch modulus.

PMID- 9653139
TI  - Basal and human papillomavirus E6 oncoprotein-induced degradation of Myc proteins
      by the ubiquitin pathway.
AB  - We have previously shown that the degradation of c-myc and N-myc in vitro is
      mediated by the ubiquitin system. However, the role of the system in targeting
      the myc proteins in vivo and the identity of the conjugating enzymes and possible
      ancillary proteins involved has remained obscure. Here we report that the
      degradation of the myc proteins in cells is inhibited by lactacystin and MG132,
      two inhibitors of the 20S proteasome. Inhibition is accompanied by accumulation
      of myc-ubiquitin conjugates. Dissection of the ancillary proteins involved
      revealed that the high-risk human papillomavirus oncoprotein E6-16 stimulates
      conjugation and subsequent degradation of the myc proteins in vitro. Expression
      of E6-16 in cells results in significant shortening of the t1/2 of the myc
      proteins with subsequent decrease in their cellular level. Analysis of the
      conjugating enzymes revealed that under basal conditions the proteins can be
      conjugated by two pairs of E2s and E3s-E2-14 kDa and E3alpha involved in the "N
      end rule" pathway, and E2-F1 (UbcH7) and E3-Fos involved also in conjugation of c
      Fos. In the presence of E6-16, a third pair, E2-F1 and E6-AP mediate conjugation
      of myc by means of a mechanism that appears to be similar to that involved in the
      targeting of p53, formation of a myc. E6.E6-AP targeting complex. It is possible
      that in certain cells E6-mediated targeting of myc prevents myc-induced apoptosis
      and thus ensures maintenance of viral infection.

PMID- 9653140
TI  - Desmosomal adhesion inhibits invasive behavior.
AB  - Recent studies of human disease and transgenic animal experiments have clearly
      demonstrated the importance of desmosomes in normal tissue architecture.
      Furthermore, desmosomal components are down-regulated in certain types of
      carcinomas, suggesting a possible role for desmosomes in suppression of invasion
      and metastasis. However, there is no functional evidence to support such a
      hypothesis. To obtain such evidence, we needed to generate desmosomal adhesion in
      an invasive cell line. We show that expression of multiple desmosomal components
      (the desmosomal cadherins, desmocollin and desmoglein, and the armadillo protein,
      plakoglobin) in nonadhesive L929 fibroblasts generates adhesion in aggregation
      assays. This adhesion is specifically blocked by short peptides corresponding to
      the putative cell adhesion recognition sites of desmocollin and desmoglein. This
      result provides an experimental demonstration of the functional importance of the
      cell adhesion recognition sites of desmocollin and desmoglein and indicates that
      both desmosomal cadherins are specifically involved in this adhesion. Moreover,
      whereas parental L929 cells are strongly invasive into collagen gels, we show
      that invasion is substantially inhibited in cells transfected with desmosomal
      components. Invasion is restored by treating the transfected cells with anti
      adhesion peptides, indicating that desmosomal adhesion specifically blocks
      invasion in culture. Our results support the suggestion that desmosomes have a
      role in suppression of tumor spreading.

PMID- 9653141
TI  - Coactivation of two different G protein-coupled receptors is essential for ADP
      induced platelet aggregation.
AB  - ADP is an important platelet agonist causing shape change and aggregation
      required for physiological hemostasis. We recently demonstrated the existence of
      two distinct G protein-coupled ADP receptors on platelets, one coupled to
      phospholipase C, P2Y1, and the other to inhibition of adenylyl cyclase, P2TAC. In
      this study, using specific antagonists for these two receptors, we demonstrated
      that concomitant intracellular signaling from both the P2TAC and P2Y1 receptors
      is essential for ADP-induced platelet aggregation. Inhibition of signaling
      through either receptor, by specific antagonists, is sufficient to block ADP
      induced platelet aggregation. Furthermore, signaling through the P2TAC receptor
      could be replaced by activation of alpha2A-adrenergic receptors. On the other
      hand, activation of serotonin receptors supplements signaling through the P2Y1
      receptor. Moreover, this mechanism of ADP-induced platelet aggregation could be
      mimicked by coactivation of two non-ADP receptors coupled to Gi and Gq, neither
      of which can cause platelet aggregation by itself. We propose that platelet
      aggregation results from concomitant signaling from both the Gi and Gq, a
      mechanism by which G protein-coupled receptors elicit a physiological response.

PMID- 9653142
TI  - ClC-5, the chloride channel mutated in Dent's disease, colocalizes with the
      proton pump in endocytotically active kidney cells.
AB  - Loss-of-function mutations of the ClC-5 chloride channel lead to Dent's disease,
      a syndrome characterized by low molecular weight proteinuria, hypercalciuria, and
      kidney stones. We show that ClC-5 is expressed in renal proximal tubule cells,
      which normally endocytose proteins passing the glomerular filter. Expression is
      highest below the brush border in a region densely packed with endocytotic
      vesicles, where ClC-5 colocalizes with the H+-ATPase and with internalized
      proteins early after uptake. In intercalated cells of the collecting duct it
      again localizes to apical intracellular vesicles and colocalizes with the proton
      pump in alpha-intercalated cells. In transfected cells, ClC-5 colocalizes with
      endocytosed alpha2-macroglobulin. Cotransfection with a GTPase-deficient rab5
      mutant leads to enlarged early endosomes that stain for ClC-5. We suggest that
      ClC-5 may be essential for proximal tubular endocytosis by providing an
      electrical shunt necessary for the efficient acidification of vesicles in the
      endocytotic pathway, explaining the proteinuria observed in Dent's disease.

PMID- 9653143
TI  - Evidence for a role of NF-kappaB in the survival of hematopoietic cells mediated
      by interleukin 3 and the oncogenic TEL/platelet-derived growth factor receptor
      beta fusion protein.
AB  - Interleukin 3 (IL-3) and other hematopoietic cytokines transduce signals that
      stimulate DNA synthesis and cell survival. In certain chronic myelomonocytic
      leukemias, a TEL/platelet-derived growth factor receptor beta (PDGFRbeta) fusion
      protein is produced as a consequence of the t(5;12) translocation. It contains
      the amino terminus of the transcription factor TEL fused to the transmembranous
      and cytoplasmic domains of the PDGFRbeta. It is oncogenic as it substitutes for
      IL-3, thus promoting cell growth and preventing apoptotic cell death. The
      mechanism by which TEL/PDGFRbeta generates survival signals remains undefined.
      Here, we report that both IL-3 and TEL/PDGFRbeta initiate a signaling cascade
      that leads to the activation of the transcriptional factor NF-kappaB. In fact,
      either cytokine deprivation of IL-3-dependent Ba/F3 cells or exposure of
      TEL/PDGFRbeta-expressing cells to the specific inhibitor of the PDGFR tyrosine
      kinase, CGP53716, caused a strong decrease in NF-kappaB activity followed by
      extensive cell death. Further, treatment with the proteasome inhibitor Z-IE(O-t
      Bu)A-leucinal suppressed IL-3 and TEL/PDGFRbeta-dependent survival. The same
      result was seen upon overexpression of an unphosphorylable form of IkappaBalpha.
      Because both conditions inactivate NF-kappaB by preventing its translocation into
      the nucleus, that process seems to be essential for cell survival in response to
      IL-3 and TEL/PDGFRbeta. Moreover, overexpression of a dominant-negative mutant of
      the protooncogene c-Myc, a downstream target of NF-kappaB, had a similar effect.
      We conclude that NF-kappaB plays an important role in maintaining cell survival
      in response to IL-3 and TEL/PDGFRbeta and that c-Myc may be a downstream effector
      mediating this effect.

PMID- 9653144
TI  - Identification of a human PTS1 receptor docking protein directly required for
      peroxisomal protein import.
AB  - The discovery of many fatal human disorders resulting from impaired peroxisomal
      protein import makes the functional characterization of human peroxins critical.
      As part of our attempt to identify novel human genes and gene products involved
      in the import of peroxisomal proteins, we raised antisera against peroxisomal
      membrane proteins. One such antiserum inhibited peroxisomal protein import in
      semipermeabilized mammalian cells. This "import inhibiting" antiserum, ab-MF3,
      specifically recognized a 57-kDa protein. Immunoblot analysis of rat liver
      subcellular fractions demonstrated that this protein was present exclusively in
      peroxisomal membranes. Functional analysis revealed that this 57-kDa molecule
      bound the PTS1 receptor, Pex5p, in ligand blots, suggesting it is a docking site
      on the peroxisomal membrane. Previous studies have identified two yeast proteins,
      Pex14p and Pex13p, as Pex5p-binding proteins. To facilitate the biochemical
      analysis of peroxisomal membrane docking proteins, we cloned and expressed the
      previously unidentified human Pex14p, as well as a human Pex13p that is 39 aa
      longer than previously reported. Recombinant Pex14p was specifically recognized
      by the "import inhibiting" ab-MF3 and bound Pex5p and the Src homology 3 (SH3)
      domain of Pex13p in ligand blots. These studies demonstrate that the ab-MF3
      immunoreactive, 57-kDa peroxisomal membrane protein is Pex14p. Furthermore, this
      peroxin interacts with Pex5p and Pex13p(SH3) and is directly required for
      peroxisomal protein import.

PMID- 9653145
TI  - Targeted expansion of genetically modified bone marrow cells.
AB  - The ability to specifically target a mitogenic signal to a population of
      genetically modified primary cells would have potential applications both for
      gene and cell therapy. Toward this end, a gene encoding a fusion protein
      containing the FK506-binding protein FKBP12, fused to the intracellular portion
      of the receptor for thrombopoietin (mpl), was introduced into primary murine bone
      marrow cells. Dimerization of this fusion protein through the addition of a
      dimeric form of the drug FK506, called FK1012, resulted in a marked proliferative
      expansion of marrow cells that was restricted to the genetically modified
      population. FK1012's proliferative effect was sustained and reversible. An
      apparent preference for differentiation along the megakaryocytic lineage was
      observed. This approach allows for the specific delivery of a mitogenic signal to
      a population of genetically modified primary cells and may have applications for
      studies in hematopoiesis and receptor biology, and for gene and cell therapy.

PMID- 9653146
TI  - Phospholipase A2-mediated activation of mitogen-activated protein kinase by
      angiotensin II.
AB  - In renal proximal tubule epithelial cells, a membrane-associated phospholipase A2
      (PLA2) is a major signaling pathway linked to angiotensin II (Ang II) type 2
      receptor (AT2). The current studies were designed to test the hypothesis that
      membrane-associated PLA2-induced release of arachidonic acid (AA) and/or its
      metabolites may serve as an upstream mediator of Ang II-induced mitogen-activated
      protein kinase (MAPK) activation. Ang II stimulated transient dose-dependent
      phosphorylation of MAPK with a maximum at 1 microM (10 min). Inhibition of PLA2
      by mepacrine diminished both AA release and MAPK phosphorylation, induced by Ang
      II. Furthermore, AA itself induced time- and dose-dependent phosphorylation of
      MAPK, supporting the importance of PLA2 as a mediator of Ang II signaling. The
      effects of both Ang II and AA on MAPK phosphorylation were protein kinase C
      independent and abolished by the inhibitor of cytochrome P450 isoenzyme,
      ketoconazole. Moreover, 5,6-epoxyeicosatrienoic acid and 14,15
      epoxyeicosatrienoic acid, the cytochrome P450-dependent metabolites of AA,
      significantly stimulated MAPK activity in renal proximal tubule epithelial cells.
      These observations document a mechanism of Ang II-induced MAPK phosphorylation,
      mediated by PLA2-dependent release of AA and cytochrome P450-dependent production
      of epoxy derivatives of AA.

PMID- 9653147
TI  - Mutagenicity of arsenic in mammalian cells: role of reactive oxygen species.
AB  - Arsenite, the trivalent form of arsenic present in the environment, is a known
      human carcinogen that lacked mutagenic activity in bacterial and standard
      mammalian cell mutation assays. We show herein that when evaluated in an assay
      (AL cell assay), in which both intragenic and multilocus mutations are
      detectable, that arsenite is in fact a strong dose-dependent mutagen and that it
      induces mostly large deletion mutations. Cotreatment of cells with the oxygen
      radical scavenger dimethyl sulfoxide significantly reduces the mutagenicity of
      arsenite. Thus, the carcinogenicity of arsenite can be explained at least in part
      by it being a mutagen that depends on reactive oxygen species for its activity.

PMID- 9653148
TI  - The Notch1 receptor is cleaved constitutively by a furin-like convertase.
AB  - The Notch receptor, which is involved in numerous cell fate decisions in
      invertebrates and vertebrates, is synthesized as a 300-kDa precursor molecule
      (p300). We show here that proteolytic processing of p300 is an essential step in
      the formation of the biologically active receptor because only the cleaved
      fragments are present at the cell surface. Our results confirm and extend recent
      reports indicating that the Notch receptor exists at the plasma membrane as a
      heterodimeric molecule, but disagree as to the nature of the protease that is
      responsible for the cleavage that takes place in the extracellular region. We
      report here that constitutive processing of murine Notch1 involves a furin-like
      convertase. We show that the calcium ionophore A23187 and the alpha1-antitrypsin
      variant, alpha 1-PDX, a known inhibitor of furin-like convertases, inhibit p300
      processing. When expressed in the furin-deficient Lovo cell line, p300 is not
      processed. In vitro digestion of a recombinant Notch-derived substrate with
      purified furin allowed mapping of the processing site to the carboxyl side of the
      sequence RQRR (amino acids 1651-1654). Mutation of these four amino acids (and of
      two secondary dibasic furin sites located nearby) completely abolished processing
      of the Notch1 receptor.

PMID- 9653149
TI  - Jasmonate-induced responses are costly but benefit plants under attack in native
      populations.
AB  - Herbivore attack is widely known to reduce food quality and to increase chemical
      defenses and other traits responsible for herbivore resistance. Inducible
      defenses are commonly thought to allow plants to forgo the costs of defense when
      not needed; however, neither their defensive function (increasing a plant's
      fitness) nor their cost-savings function have been demonstrated in nature. The
      root-produced toxin nicotine increases after herbivore attack in the native,
      postfire annual Nicotiana attenuata and is internally activated by the wound
      hormone, jasmonic acid. I treated the roots of plants with the methyl ester of
      this hormone (MeJA) to elicit a response in one member of each of 745 matched
      pairs of plants growing in native populations with different probabilities of
      attack from herbivores, and measured the lifetime production of viable seed. In
      populations with intermediate rates of attack, induced plants were attacked less
      often by herbivores and survived to produce more seed than did their uninduced
      counterparts. Previous induction did not significantly increase the fitness of
      plants suffering high rates of attack. However, if plants had not been attacked,
      induced plants produced less seed than did their uninduced counterparts.
      Jasmonate-induced responses function as defenses but are costly, and inducibility
      allows this species to forgo these costs when the defenses are unnecessary.

PMID- 9653150
TI  - Genetic evidence for a Paleolithic human population expansion in Africa.
AB  - Human populations have undergone dramatic expansions in size, but other than the
      growth associated with agriculture, the dates and magnitudes of those expansions
      have never been resolved. Here, we introduce two new statistical tests for
      population expansion, which use variation at a number of unlinked genetic markers
      to study the demographic histories of natural populations. By analyzing genetic
      variation in various aboriginal populations from throughout the world, we show
      highly significant evidence for a major human population expansion in Africa, but
      no evidence of expansion outside of Africa. The inferred African expansion is
      estimated to have occurred between 49,000 and 640,000 years ago, certainly before
      the Neolithic expansions, and probably before the splitting of African and non
      African populations. In showing a significant difference between African and non
      African populations, our analysis supports the unique role of Africa in human
      evolutionary history, as has been suggested by most other genetic work. In
      addition, the missing signal in non-African populations may be the result of a
      population bottleneck associated with the emergence of these populations from
      Africa, as postulated in the "Out of Africa" model of modern human origins.

PMID- 9653151
TI  - The evolution of primate malaria parasites based on the gene encoding cytochrome
      b from the linear mitochondrial genome.
AB  - We report a phylogenetic analysis of primate malaria parasites based on the gene
      encoding the cytochrome b protein from the mitochondrial genome. We have studied
      17 species of Plasmodium, including 14 parasitic in primates. In our analysis,
      four species were used for rooting the Plasmodium phylogenetic tree: two from
      closely related genera (Hepatocystis sp. and Haemoproteus columbae) and two other
      Apicomplexa (Toxoplasma gondii and Theileria parva). We found that primate
      malaria parasites form a monophyletic group, with the only exception being the
      Plasmodium falciparum-Plasmodium reichenowi lineage. Phylogenetic analyses that
      include two species of non-Plasmodium Haemosporina suggest that the genus
      Plasmodium is polyphyletic. We conclude that the biologic traits, such as
      periodicity and the capacity to relapse, have limited value for assessing the
      phylogenetic relationships among Plasmodium species. For instance, we found no
      evidence that would link virulence with the age of the host-parasite association.
      Our studies also reveal that the primate malaria parasites originated in Africa,
      which contradicts the presently held opinion of Southeast Asia as their center of
      origin. We propose that the radiation of Asian monkey parasites is a recent event
      where several life history traits, like differences in periodicity, appeared de
      novo.

PMID- 9653152
TI  - Molecular population genetics of the Arabidopsis CAULIFLOWER regulatory gene:
      nonneutral evolution and naturally occurring variation in floral homeotic
      function.
AB  - The evolution of interspecies differences in morphology requires sufficient
      within-species variation in developmental regulatory systems on which
      evolutionary forces can act. Molecular analyses of naturally occurring alleles of
      the Arabidopsis thaliana CAULIFLOWER locus reveal considerable intraspecific
      diversity at this floral homeotic gene, and the McDonald-Kreitman test suggests
      that this gene is evolving in a nonneutral fashion, with an excess of
      intraspecific replacement polymorphisms. The naturally occurring molecular
      variation within this floral regulatory gene is associated with functionally
      different alleles, which can be distinguished phenotypically by their
      differential ability to direct floral meristem development.

PMID- 9653153
TI  - Rice (Oryza sativa) centromeric regions consist of complex DNA.
AB  - Rice bacterial artificial chromosome clones containing centromeric DNA were
      isolated by using a DNA sequence (pSau3A9) that is present in the centromeres of
      Gramineae species. Seven distinct repetitive DNA elements were isolated from a 75
      kilobase rice bacterial artificial chromosome clone. All seven DNA elements are
      present in every rice centromere as demonstrated by fluorescence in situ
      hybridization. Six of the elements are middle repetitive, and their copy numbers
      range from approximately 50 to approximately 300 in the rice genome. Five of
      these six middle repetitive DNA elements are present in all of the Gramineae
      species, and the other element is detected only in species within the
      Bambusoideae subfamily of Gramineae. All six middle repetitive DNA elements are
      dispersed in the centromeric regions. The seventh element, the RCS2 family, is a
      tandem repeat of a 168-bp sequence that is represented approximately 6,000 times
      in the rice genome and is detected only in Oryza species. Fiber-fluorescence in
      situ hybridization analysis revealed that the RCS2 family is organized into long
      uninterrupted arrays and resembles previously reported tandem repeats located in
      the centromeres of human and Arabidopsis thaliana chromosomes. We characterized a
      large DNA fragment derived from a plant centromere and demonstrated that rice
      centromeres consist of complex DNA, including both highly and middle repetitive
      DNA sequences.

PMID- 9653154
TI  - Molecular characterization of a common fragile site (FRA7H) on human chromosome 7
      by the cloning of a simian virus 40 integration site.
AB  - Common fragile sites are chromosomal loci prone to breakage and rearrangement,
      hypothesized to provide targets for foreign DNA integration. We cloned a simian
      virus 40 integration site and showed by fluorescent in situ hybridization
      analysis that the integration event had occurred within a common aphidicolin
      induced fragile site on human chromosome 7, FRA7H. A region of 161 kb spanning
      FRA7H was defined and sequenced. Several regions with a potential unusual DNA
      structure, including high-flexibility, low-stability, and non-B-DNA-forming
      sequences were identified in this region. We performed a similar analysis on the
      published FRA3B sequence and the putative partial FRA7G, which also revealed an
      impressive cluster of regions with high flexibility and low stability. Thus,
      these unusual DNA characteristics are possibly intrinsic properties of common
      fragile sites that may affect their replication and condensation as well as
      organization, and may lead to fragility.

PMID- 9653155
TI  - Evolution of the avian sex chromosomes from an ancestral pair of autosomes.
AB  - Among the mechanisms whereby sex is determined in animals, chromosomal sex
      determination is found in a wide variety of distant taxa. The widespread but not
      ubiquitous occurrence, not even within lineages, of chromosomal sex determination
      suggests that sex chromosomes have evolved independently several times during
      animal radiation, but firm evidence for this is lacking. The most favored model
      for this process is gradual differentiation of ancestral pairs of autosomes. As
      known for mammals, sex chromosomes may have a very ancient origin, and it has
      even been speculated that the sex chromosomes of mammals and birds would share a
      common chromosomal ancestry. In this study we showed that the two genes, ATP5A1
      and CHD1, so far assigned to the female-specific W chromosome of birds both exist
      in a very closely related copy on the Z chromosome but are not pseudoautosomal.
      This indicates a common ancestry of the two sex chromosomes, consistent with the
      evolution from a pair of autosomes. Comparative mapping demonstrates, however,
      that ATP5A1 and CHD1 are not sex-linked among eutherian mammals; this is also not
      the case for the majority of other genes so far assigned to the avian Z
      chromosome. Our results suggest that the evolution of sex chromosomes has
      occurred independently in mammals and birds.

PMID- 9653156
TI  - Localization of tumor suppressor activity important in nonsmall cell lung
      carcinoma on chromosome 11q.
AB  - Loss of heterozygosity on chromosome 11q23 is observed at high frequency in human
      nonsmall cell lung carcinomas (NSCLCs), suggesting the presence of a tumor
      suppressor gene. Previous analysis of DNA from 79 patients identified a commonly
      deleted segment of 5 centimorgans. Complementation analysis was used to further
      localize a putative tumor suppressor gene. Three yeast artificial chromosome
      (YAC) clones spanning the minimal loss of heterozygosity region were modified,
      and spheroplast fusion was used to transfer them into human A549 NSCLC or murine
      Lewis lung carcinoma (LLC) cell lines. The resulting yeast x human hybrid cell
      lines containing an intact copy of a 1.6-Mb YAC, 939b12, showed reduced growth in
      vitro. Injection of parental A549 cells into athymic (nu/nu) mice resulted in
      tumor formation at 27 of 28 injection sites. In contrast, two independent 939b12
      containing cell lines formed tumors at only 3 of 20 injection sites. 939b12 also
      suppressed tumor formation by LLC NSCLC cells in nude mice, but YACs 785e12 and
      911f2, which flank 939b12, had no suppressor activity. Further localization of
      tumor suppression activity on 939b12 was accomplished by introduction of defined
      fragmentation derivatives into A549 cells and by analysis of YACs that were
      broken on transfer into LLC cells. This complementation approach localized tumor
      suppression activity to the central 700 kb of 939b12 and provides a functional
      assay for positional cloning of this tumor suppressor gene.

PMID- 9653157
TI  - sud1(+) targets cyclin-dependent kinase-phosphorylated Cdc18 and Rum1 proteins
      for degradation and stops unwanted diploidization in fission yeast.
AB  - In the fission yeast Schizosaccharomyces pombe, S phase is limited to a single
      round per cell cycle through cyclin-dependent kinase phosphorylation of critical
      replication factors, including the Cdc18 replication initiator protein. Because
      defects in Cdc18 phosphorylation lead to a hyperstable and hyperactive form of
      Cdc18 that promotes high levels of overreplication in vivo, we wished to identify
      the components of the Cdc18 proteolysis pathway in fission yeast. In this paper
      we describe one such component, encoded by the sud1(+) gene. sud1(+) shares
      homology with the budding yeast CDC4 gene and is required to prevent spontaneous
      re-replication in fission yeast. Cells lacking sud1(+) accumulate high levels of
      Cdc18 and the CDK inhibitor Rum1, because they cannot degrade these two key cell
      cycle regulators. Through genetic analysis we show that hyperaccumulation of Rum1
      contributes to re-replication in Deltasud1 cells, but is not the cause of the
      defect in Cdc18 proteolysis. Rather, Sud1 itself is associated with the ubiquitin
      pathway in fission yeast and binds to Cdc18 in vivo. Most importantly, Sud1-Cdc18
      binding requires prior phosphorylation of the Cdc18 polypeptide at CDK consensus
      sites. These results provide a biochemical mechanism for the phosphorylation
      dependent degradation of Cdc18 and other cell cycle regulators, including Rum1.
      Evolutionary conservation of the Sud1/CDC4 pathway suggests that phosphorylation
      coupled proteolysis may be a general feature of nearly all eukaryotic cell
      cycles.

PMID- 9653158
TI  - Single amino acid substitution in prokaryote polypeptide release factor 2 permits
      it to terminate translation at all three stop codons.
AB  - Prokaryotic translational release factors, RF1 and RF2, catalyze polypeptide
      release at UAG/UAA and UGA/UAA stop codons, respectively. In this study, we
      isolated a bacterial RF2 mutant (RF2*) containing an E167K substitution that
      restored the growth of a temperature-sensitive RF1 strain of Escherichia coli and
      the viability of a chromosomal RF1/RF2 double knockout. In both in vivo and in
      vitro polypeptide termination assays, RF2* catalyzed UAG/UAA termination, as does
      RF1, as well as UGA termination, showing that RF2* acquired omnipotent release
      activity. This result suggests that the E167K mutation abolished the putative
      third-base discriminator function of RF2. These findings are interpreted as
      indicating that prokaryotic and eukaryotic release factors share the same
      anticodon moiety and that only one omnipotent release factor is sufficient for
      bacterial growth, similar to the eukaryotic single omnipotent factor.

PMID- 9653159
TI  - Racial variability in the UDP-glucuronosyltransferase 1 (UGT1A1) promoter: a
      balanced polymorphism for regulation of bilirubin metabolism?
AB  - A polymorphism in the promoter of the UDP-glucuronosyltransferase 1 (UGT1A1) gene
      has been shown to cause Gilbert syndrome, a benign form of unconjugated
      bilirubinemia. Promoters containing seven thymine adenine (ta) repeats have been
      found to be less active than the wild-type six repeats, and the serum bilirubin
      levels of persons homozygous or even heterozygous for seven repeats have been
      found to be higher than those with the wild-type six repeats. We have now
      examined the genotypes in persons of Asian, African, and Caucasian ancestry.
      Although within the Caucasian ethnic group there is a strong correlation between
      promoter repeat number and bilirubin level, between ethnic groups we found that
      this relationship to be inverse. Among people of African ancestry there are, in
      addition to those with six and seven repeats, also persons who have five or eight
      repeats. Using a reporter gene we show that there is an inverse relationship
      between the number of ta repeats and the activity of the promoter through the
      range of 5-8 ta repeats. An incidental finding was a polymorphism at nucleotide 
      106, tightly linked to the (ta)5 haplotype. Serum bilirubin levels are influenced
      by many factors, both genetic and environmental. We suggest that the unstable
      UGT1A1 polymorphism may serve to "fine-tune" the plasma bilirubin level within
      population groups, maintaining it at a high enough level to provide protection
      against oxidative damage, but at a level that is sufficiently low to prevent
      kernicterus in infants.

PMID- 9653160
TI  - Identification of genes expressed in human CD34(+) hematopoietic stem/progenitor
      cells by expressed sequence tags and efficient full-length cDNA cloning.
AB  - Hematopoietic stem/progenitor cells (HSPCs) possess the potentials of self
      renewal, proliferation, and differentiation toward different lineages of blood
      cells. These cells not only play a primordial role in hematopoietic development
      but also have important clinical application. Characterization of the gene
      expression profile in CD34(+) HSPCs may lead to a better understanding of the
      regulation of normal and pathological hematopoiesis. In the present work, genes
      expressed in human umbilical cord blood CD34(+) cells were catalogued by
      partially sequencing a large amount of cDNA clones [or expressed sequence tags
      (ESTs)] and analyzing these sequences with the tools of bioinformatics. Among
      9,866 ESTs thus obtained, 4,697 (47.6%) showed identity to known genes in the
      GenBank database, 2, 603 (26.4%) matched to the ESTs previously deposited in a
      public domain database, 1,415 (14.3%) were previously undescribed ESTs, and the
      remaining 1,151 (11.7%) were mitochondrial DNA, ribosomal RNA, or repetitive (Alu
      or L1) sequences. Integration of ESTs of known genes generated a profile
      including 855 genes that could be divided into different categories according to
      their functions. Some (8.2%) of the genes in this profile were considered related
      to early hematopoiesis. The possible function of ESTs corresponding to so far
      unknown genes were approached by means of homology and functional motif searches.
      Moreover, attempts were made to generate libraries enriched for full-length
      cDNAs, to better explore the genes in HSPCs. Nearly 60% of the cDNA clones of
      mRNA under 2 kb in our libraries had 5' ends upstream of the first ATG codon of
      the ORF. With this satisfactory result, we have developed an efficient working
      system that allowed fast sequencing of 32 full-length cDNAs, 16 of them being
      mapped to the chromosomes with radiation hybrid panels. This work may lay a basis
      for the further research on the molecular network of hematopoietic regulation.

PMID- 9653161
TI  - Mutations in the Delta7-sterol reductase gene in patients with the Smith-Lemli
      Opitz syndrome.
AB  - The Smith-Lemli-Opitz syndrome (SLOS) is an inborn disorder of sterol metabolism
      with characteristic congenital malformations and dysmorphias. All patients suffer
      from mental retardation. Here we identify the SLOS gene as a Delta7-sterol
      reductase (DHCR7, EC 1.3.1. 21) required for the de novo biosynthesis of
      cholesterol. The human and murine genes were characterized and assigned to
      syntenic regions on chromosomes 11q13 and 7F5 by fluorescense in situ
      hybridization. Among the mutations found in patients with the SLOS, are missense
      (P51S, T93M, L99P, L157P, A247V, V326L, R352W, C380S, R404C, and G410S), nonsense
      (W151X), and splice site (IVS8-1G>C) mutations as well as an out of frame
      deletion (720-735 del). The missense mutations L99P, V326L, R352W, R404C, and
      G410S reduced heterologous protein expression by >90%. Our results strongly
      suggest that defects in the DHCR7 gene cause the SLOS.

PMID- 9653162
TI  - HD mice: a novel mouse mutant with a specific defect in the generation of CD4(+)
      T cells.
AB  - We have identified a spontaneous mutation in mice, which we term HD for "helper T
      cell deficient." This mouse is distinguished by the virtual absence of peripheral
      T cells of the CD4(+)8(-) major histocompatibility complex (MHC) class II
      restricted T helper subset due to a specific block in thymic development. The
      developmental defect is selective for CD4(+)8(-) cells; the maturation of CD4(
      )8(+) and gamma delta T cells is normal. The autosomal recessive mutation
      underlying the HD phenotype is unrelated to MHC class II, since it segregates
      independently of the MHC class II locus. Moreover, the HD phenotype is not caused
      by a defect of the CD4 gene. Bone marrow transfer experiments demonstrate that
      the defect is intrinsic to cells of the hematopoietic lineage, i.e., most likely
      to developing thymocytes themselves. The frequency of CD4(+)8(low) intermediate
      cells is markedly increased in HD mice, suggesting that class II-restricted
      thymocytes are arrested at this stage. This is the first genetic defect of its
      kind to be described in the mouse and may prove highly informative in
      understanding the molecular pathways underlying lineage commitment.

PMID- 9653163
TI  - Altered peptide ligands induce quantitatively but not qualitatively different
      intracellular signals in primary thymocytes.
AB  - Interaction of the T cell receptor (TCR) with peptide/major histocompatibility
      complexes (MHC) in the thymus is of critical importance for developing
      thymocytes. In a previous study, we described an antagonist peptide that
      inhibited negative selection of transgenic thymocytes induced by an agonist
      peptide. In this study we show that this antagonist peptide can induce positive
      selection of CD8(+) thymocytes more efficiently than the agonist or the weak
      agonist peptides, whereas the opposite is true for their ability to cause
      negative selection. The intracellular signals induced in thymocytes by such
      peptides after TCR ligation was examined in CD4(+)8(+) double-positive thymocytes
      from F5/beta2mo/Rag-1(o) transgenic mice. TCR ligation with either the agonist,
      weak agonist, or antagonist peptide variants resulted in hyperphosphorylation of
      CD3zeta, CD3epsilon, ZAP-70, Syk, Vav, SLP-76, and pp36-38. The extent of
      phosphorylation of these intracellular proteins correlated with the efficiency
      with which the peptide analogs induced apoptosis of immature thymocytes.
      Unexpectedly, there was no correlation between the upstream TCR signaling
      pathways analyzed and the capacity of the different peptides to induce positive
      selection.

PMID- 9653164
TI  - Intrathymic selection of NK1.1(+)alpha/beta T cell antigen receptor (TCR)+ cells
      in transgenic mice bearing TCR specific for chicken ovalbumin and restricted to I
      Ad.
AB  - Generation and negative selection of NK1.1(+)alpha/beta T cell receptor (TCR)+
      thymocytes were analyzed using TCR-transgenic (B10. D2 x DO10)F1 and (C57BL/6 x
      DO10)F1 mice and Rag-1(-/-)/DO10 mice, which had been established by breeding and
      backcrossing between Rag-1(-/-) and DO10 mice. Almost all T cells from these mice
      were shown to bear Valpha13/Vbeta8.2 that is specific for chicken ovalbumin
      (cOVA) and restricted to I-Ad. A normal proportion of the NK1.1(+)
      Valpha13/Vbeta8.2(+) thymocytes was generated in these mice. However, the actual
      cell number of both NK1.1(+) and NK1.1(-) thymocytes in I-Ad/d mice (positive
      selecting background) was larger than that in I-Ab/d mice (negative selecting
      background). Markedly low but significant proportions of NK1.1(+)
      Valpha13/Vbeta8.2(+) cells were detected in the spleens from I-Ad/d and I-Ab/d
      mice. It was shown that the splenic NK1.1(+) T cells of the I-Ab/d mice were
      anergized against stimulation through TCR. When (B10.D2 x DO10)F1 and (C57BL/6 x
      DO10)F1 mice were given cOVA, extensive or intermediate elimination of
      NK1.1(+)alpha/betaTCR+ thymocytes was induced in I-Ad/d or I-Ab/d mice,
      respectively. However, the clonal elimination was not as complete as that seen in
      the major NK1.1(-) thymocyte population. The present findings indicate that
      normal generation of NK1.1(+)alpha/betaTCR+ thymocytes occurs in the absence of
      Valpha14-Jalpha281 and that substantial negative selection operates on the
      NK1.1(+)alpha/betaTCR+ cells.

PMID- 9653165
TI  - The CC chemokine 6Ckine binds the CXC chemokine receptor CXCR3.
AB  - We cloned the mouse homologue of the chemokine receptor CXCR3, which is located
      in mouse chromosome X. We screened a large panel of chemokines for their ability
      to induce a calcium flux in mouse CXCR3-transfected cells and identified a new
      ligand for this receptor, the recently reported CC chemokine 6Ckine. This
      represents an example of a CC chemokine, which binds to a CXC chemokine receptor.
      Like other ligands of this receptor, 6Ckine has angiostatic properties. 6Ckine is
      known to chemoattract T cells. In line with this, CXCR3 is expressed
      preferentially in Th1 cells and in lymphoid organs of the IL-10(-/-) mouse that
      develops chronic colitis. Its ability to attract T cells as well as its
      angiostatic properties suggest that 6Ckine may be an effective anti-tumor agent.

PMID- 9653166
TI  - Efficient adenoviral infection with IkappaB alpha reveals that macrophage tumor
      necrosis factor alpha production in rheumatoid arthritis is NF-kappaB dependent.
AB  - Tumor necrosis factor (TNF) alpha has been shown to be a major therapeutic target
      in rheumatoid arthritis with the success of anti-TNFalpha antibody clinical
      trials. Although signaling pathways leading to TNFalpha expression have been
      studied in some detail, there is evidence for considerable differences between
      individual cell types. This prompted us to investigate the intracellular
      signaling pathways that result in increased TNFalpha synthesis from macrophages
      in the diseased synovial joint tissue. Using an adenoviral system in vitro we
      report the successful delivery of genes to more than 95% of normal human
      macrophages. This permitted us to show, by using adenoviral transfer of IkappaB
      alpha, the natural inhibitor of NF-kappaB, that induction of TNFalpha in normal
      human macrophages by lipopolysaccharide, but not by some other stimuli, was
      inhibited by 80%. Furthermore the spontaneous production of TNFalpha from human
      rheumatoid joint cell cultures was inhibited by 75%, indicating that the NF
      kappaB pathway is an essential step for TNFalpha synthesis in synovial
      macrophages and demonstrating that NF-kappaB should be an effective therapeutic
      target in this disease.

PMID- 9653167
TI  - Poliovirus vaccine vectors elicit antigen-specific cytotoxic T cells and protect
      mice against lethal challenge with malignant melanoma cells expressing a model
      antigen.
AB  - Recombinant polioviruses expressing foreign antigens may provide a convenient
      vaccine vector system to induce protective immunity against diverse pathogens.
      Replication-competent chimeric viruses can be constructed by inserting foreign
      antigenic sequences within the poliovirus polyprotein. When inserted sequences
      are flanked by poliovirus protease recognition sites the recombinant polyprotein
      is processed to mature and functional viral proteins plus the exogenous antigen.
      It previously has been shown that poliovirus recombinants can induce antibody
      responses against the inserted sequences but it is not known whether poliovirus
      or vaccine vectors derived from it can elicit effective cytotoxic T lymphocyte
      (CTL) responses. To examine the ability of the recombinant poliovirus to induce
      CTL responses, a segment of the chicken ovalbumin gene, which includes the H2-Kb
      restricted CTL epitope SIINFEKL, was cloned at the junction of the P1 and P2
      regions. This recombinant virus replicated with near wild-type efficiency in
      culture and stably expressed high levels of the ovalbumin antigen. Murine and
      primate cells infected with the recombinant virus appropriately processed the
      SIINFEKL epitope and presented it within major histocompatibility complex class I
      molecules. Inoculation of mice with recombinant poliovirus that expresses
      ovalbumin elicits an effective specific CTL response. Furthermore, vaccination
      with these recombinant poliovirus induced protective immunity against challenge
      with lethal doses of a malignant melanoma cell line expressing ovalbumin.

PMID- 9653168
TI  - Interleukin 6 plays a key role in the development of antigen-induced arthritis.
AB  - To investigate the direct role of interleukin (IL) 6 in the development of
      rheumatoid arthritis, IL-6-deficient (IL-6 -/-) mice were backcrossed for eight
      generations into C57BL/6 mice, a strain of mice with a genetic background of
      susceptibility for antigen-induced arthritis (AIA). Both histological and
      immunological comparisons were made between IL-6-deficient (IL-6 -/-) mice and
      wild-type (IL-6 +/+) littermates after the induction of AIA. Although all IL-6
      +/+ mice developed severe arthritis, only mild arthritis was observed in IL-6 -/-
      mice. Safranin O staining demonstrated that articular cartilage was well
      preserved in IL-6 -/- mice, whereas it was destroyed completely in IL-6 +/+ mice.
      In addition, comparable mRNA expression for both IL-1beta and tumor necrosis
      factor alpha, but not for IL-6, was detected in the inflamed joints of IL-6 -/-
      mice, suggesting that IL-6 may play a more crucial role in cartilage destruction
      than either IL-1beta or tumor necrosis factor alpha. In immunological
      comparisons, both antigen-specific in vitro proliferative response in lymph node
      cells and in vivo antibody production were elicited in IL-6 -/- mice, but they
      were reduced to less than half of that found in IL-6 +/+ mice. Lymph node cells
      of IL-6 -/- mice produced many more Th2 cytokines than did IL-6 +/+ mice with
      either antigen-specific or nonspecific stimulation in in vitro culture. Taken
      together, these results indicate that IL-6 may play a key role in the development
      of AIA at the inductive as well as the effector phase, and the blockade of IL-6
      is possibly beneficial in the treatment of rheumatoid arthritis.

PMID- 9653169
TI  - Human parvovirus B19 as a causative agent for rheumatoid arthritis.
AB  - Human parvovirus B19 (B19) DNA was detected in the synovial tissues in 30 of 39
      patients with rheumatoid arthritis (RA), and infrequently in those with
      osteoarthritis and traumatic joints. On the other hand, the expression of the B19
      antigen VP-1 was specific (27/27) in RA synovium with active synovial lesions,
      but not in osteoarthritis and controls. The target cells of B19 were macrophages,
      follicular dendritic cells, T cells, and B cells, but not synovial lining cells
      in the synovium. B19-negative bone marrow cells, tonsil cells, and macrophage
      cell line U-937 cells became positive for the expression of VP-1, and more
      productive for interleukin 6 and tumor necrosis factor alpha when cocultured with
      RA synovial cells. The expression of VP-1 and the production of interleukin 6 and
      tumor necrosis factor alpha was significantly inhibited by the addition of
      neutralizing antibody for B19, suggesting that B19 detected in RA synovial cells
      is infective. B19 is involved in the initiation and perpetuation of RA synovitis,
      leading to joint lesions.

PMID- 9653170
TI  - Targeted disruption of the interferon-gamma receptor 2 gene results in severe
      immune defects in mice.
AB  - To study the role of the interferon- (IFN) gammaR2 chain in IFN-gamma signaling
      and immune function, IFN-gammaR2-deficient mice have been generated and
      characterized. Cells derived from IFN-gammaR2 -/- mice are unable to activate
      either JAK/STAT signaling proteins or gene transcription in response to IFN
      gamma. The lack of IFN-gamma responsiveness alters IFN-gamma-induced Ig class
      switching by B cells from these mice. In vitro cultures of T cells demonstrate
      that the T cells from the IFN-gammaR2 -/- mice have a defect in Th1 cell
      differentiation. The IFN-gammaR2 (-/-) mice also produce lower amounts of IFN
      gamma in response to antigenic challenge. In addition, IFN-gammaR2 -/- mice are
      defective in contact hypersensitivity and are highly susceptible to infection by
      Listeria monocytogenes. These results demonstrate that the IFN-gammaR2 is
      essential for IFN-gamma-mediated immune responses in vivo.

PMID- 9653171
TI  - Retroviral transduction of TLS-ERG initiates a leukemogenic program in normal
      human hematopoietic cells.
AB  - Many chimeric oncogenes have been identified by virtue of the association between
      chromosomal translocation and specific human leukemias. However, the biological
      mechanism by which these oncogenes disrupt the developmental program of normal
      human hematopoietic cells during the initiation of the leukemogenic process is
      poorly understood due to the absence of an appropriate experimental system to
      study their function. Here, we report that retroviral transduction of TLS-ERG, a
      myeloid leukemia-associated fusion gene, to human cord blood cells results in
      altered myeloid and arrested erythroid differentiation and a dramatic increase in
      the proliferative and self-renewal capacity of transduced myeloid progenitors.
      Thus, TLS-ERG expression alone induced a leukemogenic program that exhibited
      similarities to the human disease associated with this translocation. These
      results provide an experimental examination of the early stages of the human
      leukemogenic process induced by a single oncogene and establish a paradigm to
      functionally assay putative leukemogenic genes in normal human hematopoietic
      cells.

PMID- 9653172
TI  - Propagation and recovery of intact, infectious Epstein-Barr virus from
      prokaryotic to human cells.
AB  - With current techniques, genetic alterations of herpesviruses are difficult to
      perform, mostly because of the large size of their genomes. To solve this
      problem, we have designed a system that allows the cloning of any gamma
      herpesvirus in Escherichia coli onto an F factor-derived plasmid. Immortalized B
      cell lines were readily established with recombinant Epstein-Barr virus (EBV),
      demonstrating that the F factor-cloned EBV genome has all the characteristics of
      wild-type EBV. Because any genetic modification is possible in E. coli, this
      experimental approach opens the way to the genetic analysis of all EBV functions.
      Moreover, it is now feasible to generate attenuated EBV strains in vitro such
      that vaccine strains can be designed. Because we incorporated the genes for
      hygromycin resistance and green fluorescent protein onto the E. coli cloned EBV
      genome, the still open question of the EBV target cells other than B lymphocytes
      will be addressed.

PMID- 9653173
TI  - Autoregulation of thyroid-specific gene transcription by thyroglobulin.
AB  - Thyroglobulin (TG), the primary synthetic product of the thyroid, is the
      macromolecular precursor of thyroid hormones. TG synthesis, iodination, storage
      in follicles, and degradation control thyroid hormone formation and secretion
      into the circulation. Thyrotropin (TSH), via its receptor (TSHR), increases
      thyroid hormone levels by up-regulating expression of the sodium iodide symporter
      (NIS), thyroid peroxidase (TPO), and TG genes. TSH does this by modulating the
      expression and activity of several thyroid-specific transcription factors,
      thyroid transcription factor (TTF)-1, TTF-2, and Pax-8, which coordinately
      regulate NIS, TPO, TG, and the TSHR. Major histocompatibility complex class I
      gene expression, which also is regulated by TTF-1 and Pax-8 in the thyroid, is
      decreased simultaneously. This helps maintain self-tolerance in the face of TSH
      increased gene products necessary for thyroid hormone formation. In this report
      we show that follicular TG counter-regulates TSH-increased, thyroid-specific gene
      transcription by suppressing expression of the TTF-1, TTF-2, and Pax-8 genes.
      This decreases expression of the TG, TPO, NIS, and TSHR genes, but increases
      class I expression. TG acts transcriptionally, targeting, for example, a sequence
      within 1.15 kb of the 5' flanking region of TTF-1. TG does not affect ubiquitous
      transcription factors regulating TG, TPO, NIS, and/or TSHR gene expression. The
      inhibitory effect of TG on gene expression is not duplicated by thyroid hormones
      or iodide and may be mediated by a TG-binding protein on the apical membrane. We
      hypothesize that TG-initiated, transcriptional regulation of thyroid-restricted
      genes is a normal, feedback, compensatory mechanism that limits follicular
      function and contributes to follicular heterogeneity.

PMID- 9653174
TI  - Evidence for multiclonality in multicentric Kaposi's sarcoma.
AB  - Kaposi's sarcoma (KS) develops in a variety of clinical states and is the most
      common tumor seen in patients with HIV-1 infection. KS develops as a multifocal
      mucocutaneous disease with subsequent spread to visceral organs, and it has been
      argued to be a benign proliferation caused by its multifocality at initial
      presentation, lack of aneuploidy, and spontaneous regression upon withdrawal of
      immunosuppressive agents in iatrogenically induced disease. We wished to
      determine whether KS lesions are clonal, indicative of a true neoplasm. Also, we
      tested whether multifocal KS lesions are clonally related, derived from a common
      progenitor cell or of independent cellular origin. We studied the X-chromosome
      inactivation pattern of the human androgen receptor gene in tumor biopsies of
      women with KS. This procedure tests for the clonality of a tissue specimen, a
      hallmark of neoplasia. Each specimen was microdissected to minimize normal cell
      contamination. Of 12 evaluable cases, 10 were HIV-seropositive and 2 were HIV
      seronegative. Twenty-four biopsies from the 12 patients were examined. Five cases
      were consistent with individual KS lesions being clonal. In two cases, multiple
      KS specimens derived from the individual patients had different androgen receptor
      alleles inactivated, proving unequivocally that these KS lesions arose
      independently from distinct transformed cells. In seven cases, only a polyclonal
      pattern of inactivation was observed, whereas two others had tumor areas of both
      clonal and polyclonal inactivation patterns. These findings suggest that KS can
      be a clonal neoplasm, and in some of the cases multiple KS lesions in a given
      patient can arise from independent cellular origins and acquire clonal
      characteristics. The polyclonal inactivation pattern observed in other KS lesions
      may represent a premalignant stage or false negative results.

PMID- 9653175
TI  - Activation of epsilon protein kinase C correlates with a cardioprotective effect
      of regular ethanol consumption.
AB  - In addition to decreasing the incidence of myocardial infarction, recent
      epidemiological data suggest that regular alcohol consumption improves survival
      after myocardial infarction. We recently found that chronic ethanol exposure
      induces long-term protection against cardiac ischemia-reperfusion injury, which
      improves myocardial recovery after infarction. Furthermore, this cardioprotection
      by ethanol is mediated through myocyte adenosine A1 receptors. We now determine
      the role of protein kinase C (PKC) in ethanol's protective effect against
      ischemia-reperfusion injury. Using perfused hearts of ethanol-fed guinea pigs, we
      find that improved contractile recovery and creatine kinase release after
      ischemia-reperfusion are abolished by PKC inhibition with chelerythrine. Western
      blot analysis and immunofluorescence localization demonstrate that regular
      ethanol consumption causes sustained translocation (activation) of epsilonPKC,
      but not delta or alphaPKC. This same isozyme is directly implicated in ischemic
      preconditioning's protection against ischemia-reperfusion injury. Our findings
      suggest (i) that regular ethanol consumption induces long-term cardioprotection
      through sustained translocation of epsilonPKC and (ii) that PKC activity is
      necessary at the time of ischemia to mediate ethanol's protective effect against
      ischemia-reperfusion injury. Studying this selective effect of ethanol on
      epsilonPKC activation may lead to new therapies to protect against ischemia
      reperfusion injury in the heart and other organ systems.

PMID- 9653176
TI  - Cannabidiol and (-)Delta9-tetrahydrocannabinol are neuroprotective antioxidants.
AB  - The neuroprotective actions of cannabidiol and other cannabinoids were examined
      in rat cortical neuron cultures exposed to toxic levels of the excitatory
      neurotransmitter glutamate. Glutamate toxicity was reduced by both cannabidiol, a
      nonpsychoactive constituent of marijuana, and the psychotropic cannabinoid (
      )Delta9-tetrahydrocannabinol (THC). Cannabinoids protected equally well against
      neurotoxicity mediated by N-methyl-D-aspartate receptors, 2-amino-3-(4-butyl-3
      hydroxyisoxazol-5-yl)propionic acid receptors, or kainate receptors. N-methyl-D
      aspartate receptor-induced toxicity has been shown to be calcium dependent; this
      study demonstrates that 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic
      acid/kainate receptor-type neurotoxicity is also calcium-dependent, partly
      mediated by voltage sensitive calcium channels. The neuroprotection observed with
      cannabidiol and THC was unaffected by cannabinoid receptor antagonist, indicating
      it to be cannabinoid receptor independent. Previous studies have shown that
      glutamate toxicity may be prevented by antioxidants. Cannabidiol, THC and several
      synthetic cannabinoids all were demonstrated to be antioxidants by cyclic
      voltametry. Cannabidiol and THC also were shown to prevent hydroperoxide-induced
      oxidative damage as well as or better than other antioxidants in a chemical
      (Fenton reaction) system and neuronal cultures. Cannabidiol was more protective
      against glutamate neurotoxicity than either ascorbate or alpha-tocopherol,
      indicating it to be a potent antioxidant. These data also suggest that the
      naturally occurring, nonpsychotropic cannabinoid, cannabidiol, may be a
      potentially useful therapeutic agent for the treatment of oxidative neurological
      disorders such as cerebral ischemia.

PMID- 9653177
TI  - Nanobacteria: an alternative mechanism for pathogenic intra- and extracellular
      calcification and stone formation.
AB  - Calcium phosphate is deposited in many diseases, but formation mechanisms remain
      speculative. Nanobacteria are the smallest cell-walled bacteria, only recently
      discovered in human and cow blood and commercial cell culture serum. In this
      study, we identified with energy-dispersive x-ray microanalysis and chemical
      analysis that all growth phases of nanobacteria produce biogenic apatite on their
      cell envelope. Fourier transform IR spectroscopy revealed the mineral as
      carbonate apatite. The biomineralization in cell culture media resulted in
      biofilms and mineral aggregates closely resembling those found in tissue
      calcification and kidney stones. In nanobacteria-infected fibroblasts, electron
      microscopy revealed intra- and extracellular acicular crystal deposits, stainable
      with von Kossa staining and resembling calcospherules found in pathological
      calcification. Previous models for stone formation have led to an hypothesis that
      elevated pH due to urease and/or alkaline phosphatase activity is a lithogenic
      factor. Our results indicate that carbonate apatite can be formed without these
      factors at pH 7.4, at physiological phosphate and calcium concentrations.
      Nanobacteria can produce apatite in media mimicking tissue fluids and glomerular
      filtrate and provide a unique model for in vitro studies on calcification.

PMID- 9653178
TI  - Depletion of intracellular Ca2+ stores, phosphorylation of eIF2alpha, and
      sustained inhibition of translation initiation mediate the anticancer effects of
      clotrimazole.
AB  - Regulation of translation initiation plays a critical role in the control of cell
      growth and division in eukaryotic cells. Translation of many growth regulatory
      proteins including cyclins depends critically on translation initiation factors
      because their mRNAs are translated inefficiently. We report that clotrimazole, a
      potent antiproliferative agent both in vitro and in vivo, inhibits cell growth by
      interfering with translation initiation. In particular, clotrimazole causes a
      sustained depletion of intracellular Ca2+ stores, which results in activation of
      PKR, phosphorylation of eIF2alpha, and thereby in inhibition of protein synthesis
      at the level of translation initiation. Consequently, clotrimazole preferentially
      decreases the expression of the growth promoting proteins cyclin A, E and D1,
      resulting in inhibition of cyclin-dependent kinase activity and blockage of cell
      cycle in G1.

PMID- 9653179
TI  - Mutagenesis associated with nitric oxide production in macrophages.
AB  - To better understand the mechanisms through which persistent
      infections/inflammation increase cancer risks, we assessed the potential
      genotoxic properties of NO produced by macrophages. We recently showed that mouse
      macrophage RAW264.7 cells were capable of resuming exponential growth after
      stimulation for NO production by interferon-gamma (IFN-gamma) and/or
      lipopolysaccharide. Here, we report that increases in mutant fraction (MF) in the
      endogenous, X-linked, hprt gene of the cells are associated with NO exposure.
      Cells stimulated with 100 units/ml IFN-gamma continuously for 14 and 23 days
      produced a total of 9.8 and 14 micromol of NO per 10(7) cells, respectively. MFs
      in the hprt gene of NO-producing cells were 16.6 and 31.3 x 10(-5), respectively,
      compared with 2.2 and 2.5 x 10(-5) in untreated cells. Addition of an NO synthase
      inhibitor, N-monomethyl-L-arginine, to the culture medium decreased NO production
      and MF by 90% and 85%, respectively. Reverse transcription-PCR and DNA sequencing
      revealed that NO-associated hprt mutations did not differ significantly from
      those arising spontaneously, with the exception that certain small
      deletions/insertions and multiple exon deletions were observed only in the
      former. MF also increased significantly in cells stimulated for only 4 days with
      lipopolysaccharide plus IFN-gamma for higher rates of NO production. The types
      and proportion of hprt mutations induced under these conditions were strikingly
      similar to those associated with long-term NO exposure. These results indicate
      that NO exposure results in gene mutations in RAW264.7 cells through mechanisms
      yet to be identified and may also contribute to spontaneous mutagenesis.

PMID- 9653180
TI  - Functional and physical interactions of the ARF tumor suppressor with p53 and
      Mdm2.
AB  - The INK4a-ARF locus encodes two proteins, p16(INK4a) and p19(ARF), that restrain
      cell growth by affecting the functions of the retinoblastoma protein and p53,
      respectively. Disruption of this locus by deletions or point mutations is a
      common event in human cancer, perhaps second only to the loss of p53. Using
      insect cells infected with baculovirus vectors and NIH 3T3 fibroblasts infected
      with ARF retrovirus, we determined that mouse p19(ARF) can interact directly with
      p53, as well as with the p53 regulator mdm2. ARF can bind p53-DNA complexes, and
      it depends upon functional p53 to transcriptionally induce mdm2 and the cyclin
      dependent kinase inhibitor p21(Cip1), and to arrest cell proliferation. Binding
      of p19(ARF) to p53 requires the ARF N-terminal domain (amino acids 1-62) that is
      necessary and sufficient to induce cell cycle arrest. Overexpression of p19(ARF)
      in wild type or ARF-null mouse embryo fibroblasts increases the half-life of p53
      from 15 to approximately 75 min, correlating with an increased p53-dependent
      transcriptional response and growth arrest. Surprisingly, when overexpressed at
      supra-physiologic levels after introduction into ARF-null NIH 3T3 cells or mouse
      embryo fibroblasts, the p53 protein is handicapped in inducing this checkpoint
      response. In this setting, reintroduction of p19(ARF) restores p53's ability to
      induce p21(Cip1) and mdm2, implying that, in addition to stabilizing p53, ARF
      modulates p53-dependent function through an additional mechanism.

PMID- 9653181
TI  - Tissue factor transcription driven by Egr-1 is a critical mechanism of murine
      pulmonary fibrin deposition in hypoxia.
AB  - Local hypoxemia and stasis trigger thrombosis. We have demonstrated previously
      that in a murine model of normobaric hypoxia pulmonary fibrin deposition is a
      result of expression of tissue factor, especially in oxygen-deprived mononuclear
      phagocytes (MPs). We now show that transcription factor early-growth-response
      gene product (Egr-1) is rapidly activated in hypoxia, both in vitro and in vivo,
      and is responsible for transcription and expression of tissue factor in hypoxic
      lung. MPs and HeLa cells subjected to hypoxia (pO2 approximately 13 torr) had
      increased levels of tissue factor transcripts (approximately 18-fold) and an
      increased rate of transcription (approximately 15-fold), based on nuclear run-on
      analysis. Gel-shift analysis of nuclear extracts from hypoxic MPs and HeLa cells
      demonstrated increased DNA-binding activity at the serum response region (SRR; 
      111/+14 bp) of the tissue factor promoter at Egr-1 motifs. Using 32P-labeled Egr
      consensus oligonucleotide, we observed induction of DNA-binding activity in
      nuclear extracts from hypoxic lung and HeLa cells because of activation of Egr-1,
      by means of supershift analysis. Transient transfection of HeLa cells with
      chimeric plasmids containing wild-type or mutant SRR from the tissue factor
      promoter showed that intact Sp1 sites are necessary for basal promoter activity,
      whereas the integrity of Egr-1 sites was required for hypoxia-enhanced
      expression. A central role for Egr-1 in hypoxia-mediated tissue factor expression
      was confirmed by experiments with homozygous Egr-1 null mice; wild-type mice
      subjected to oxygen deprivation expressed tissue factor and showed fibrin
      deposition, but hypoxic homozygous Egr-1 null mice displayed neither tissue
      factor nor fibrin. These data delineate a novel biology for hypoxia-induced
      fibrin deposition, in which oxygen deprivation-induced activation of Egr-1,
      resulting in expression of tissue factor, has an unexpected and central role.

PMID- 9653182
TI  - In vivo transfer of barley stripe mosaic hordeivirus ribonucleotides to the 5'
      terminus of maize stripe tenuivirus RNAs.
AB  - The Tenuivirus maize stripe virus (MStV) shares many properties with viruses in
      the genus Phlebovirus of the family Bunyaviridae. Besides genome organization and
      gene expression strategies, one property shared by these plant- and vertebrate
      infecting viruses is that transcription gives rise to virus-specific mRNAs
      containing nonviral 5'-terminal nucleotide sequences. The 5'-terminal nucleotides
      are believed to be derived from host mRNA sequences as a result of "cap
      snatching." We investigated whether specific nucleotide sequences could serve as
      primer donors for cap-snatching in vivo. Barley (Hordeum vulgare) plants were
      singly and doubly infected with MStV and the Hordeivirus barley stripe mosaic
      virus (BSMV). A reverse transcription-PCR assay was used to identify chimeric
      BSMV/MStV RNAs. Specific reverse transcription-PCR products were detected from
      doubly infected plants by using one PCR primer corresponding to the 5' termini of
      the BSMV RNAs (alpha, beta, and gamma) and a second primer complementary to MStV
      RNA 4. The resulting cDNAs were cloned, and nucleotide sequence analysis showed
      them to be chimeric, containing BSMV 5'-terminal sequences as well as MStV RNA 4
      sequences. All clones contained the BSMV RNA 5' primer nucleotide sequence, but
      they also showed characteristics common to Tenuivirus mRNAs. More than 80% of the
      clones contained BSMV RNA nucleotides not present on the PCR primer. Several
      lacked the exact 5' terminus of MStV RNA 4, a feature also seen for viruses in
      the Bunyaviridae. These data show that heterologous virus RNAs (BSMV) can serve
      as primer donors for MStV mRNA capped RNA-primed transcription in doubly infected
      plants.

PMID- 9653183
TI  - Two distinct forms of long-term depression coexist at the mossy fiber-CA3 synapse
      in the hippocampus during development.
AB  - During a critical period of postnatal development, between postnatal days 6 and
      14, a high-frequency stimulation train (100 Hz for 1 s) to the mossy fibers
      induces a long-term depression (LTD) of synaptic efficacy of 29 +/- 5.2%. This
      form of LTD is homosynaptic. It is independent of the activation of N-methyl-D
      aspartate or metabotropic glutamate receptors but needs an increase in calcium
      into the postsynaptic cell for its induction. At the same synapse LTD also could
      be induced by low-frequency stimulation of the mossy fibers (1 Hz for 15 min). In
      this case the magnitude of the depression is 37 +/- 4.2%. This form of LTD is N
      methyl-D-aspartate independent but requires the activation of metabotropic
      glutamate receptors because it is prevented by (S)-alpha-methyl-4
      carboxyphenylglycine (1 mM). Moreover its induction appears to be presynaptic,
      because, in contrast with the high-frequency one, it is not blocked by loading
      the postsynaptic cell with the calcium chelator EGTA or bis-(-o
      aminophenoxy)ethane-N, N,N',N'-tetraacetic acid (BAPTA). Saturation of one form
      of LTD does not occlude the other, suggesting that high and low frequency-induced
      LTD depend on distinct mechanisms of induction and expression. Quantal (noise
      deconvolution) analysis of minimal excitatory postsynaptic potentials shows,
      similarly to high-frequency LTD, a decrease in quantal content without any change
      in quantal size after low-frequency LTD, suggesting that in both forms of LTD the
      site where maintenance mechanisms are located is presynaptic.

PMID- 9653184
TI  - Neuroblast pattern formation: regulatory DNA that confers the vnd/NK-2 homeobox
      gene pattern on a reporter gene in transgenic lines of Drosophila.
AB  - DNA fragments -0.57, -2.2, -2.9, -5.3, and -8.4 kb in length from the upstream
      regulatory region of the vnd/NK-2 gene were cloned in the 5'-flanking region of a
      beta-galactosidase (beta-gal) reporter gene in the P-element pCaSpeR-AUG-beta
      gal, and the effects of the DNA on the pattern and time of expression of beta-gal
      were determined in transgenic embryos. Embryos from 11 lines transformed with 
      8.4 kb of vnd/NK-2 regulatory DNA expressed beta-gal patterns that closely
      resemble those of vnd/NK-2. In embryos from four lines transformed with -5.3 kb
      of vnd/NK-2 DNA, beta-gal was found in the normal vnd/NK-2 pattern in the nerve
      cord but not in part of the cephalic region. beta-Gal patterns in embryos from
      transgenic lines containing -0.57, -2.2, or -2.9 kb of vnd/NK-2 DNA did not
      resemble vnd/NK-2. Null vnd/NK-2 mutant embryos containing the homozygous P
      element p[-8.4 to +0.34 beta-gal] expressed little beta-gal in contrast to
      siblings with a wild-type vnd/NK-2 gene. We conclude that (i) the 8.4-kb DNA
      fragment from the vnd/NK-2 gene contains the nucleotide sequences required to
      generate the normal pattern of vnd/NK-2 gene expression, sequences that may be
      involved in the switch between neuroblast vs. epidermoblast pathways of
      development, (ii) the 5'-flanking region of the vnd/NK-2 gene between -5.3 and 
      8. 4 kb is required for vnd/NK-2 gene expression in the most dorsoanterior part
      of the cephalic region, and (iii) vnd/NK-2 protein is required, directly or
      indirectly, for maintenance of vnd/NK-2 gene expression.

PMID- 9653185
TI  - Different patterns of truncated prion protein fragments correlate with distinct
      phenotypes in P102L Gerstmann-Straussler-Scheinker disease.
AB  - The clinicopathological phenotype of the Gerstmann-Straussler-Scheinker disease
      (GSS) variant linked to the codon 102 mutation in the prion protein (PrP) gene
      (GSS P102L) shows a high heterogeneity. This variability also is observed in
      subjects with the same prion protein gene PRNP haplotype and is independent from
      the duration of the disease. Immunoblot analysis of brain homogenates from GSS
      P102L patients showed two major protease-resistant PrP fragments (PrP-res) with
      molecular masses of approximately 21 and 8 kDa, respectively. The 21-kDa
      fragment, similar to the PrP-res type 1 described in Creutzfeldt-Jakob disease,
      was found in five of the seven subjects and correlated with the presence of
      spongiform degeneration and "synaptic" pattern of PrP deposition whereas the 8
      kDa fragment, similar to those described in other variants of GSS, was found in
      all subjects in brain regions showing PrP-positive multicentric amyloid deposits.
      These data further indicate that the neuropathology of prion diseases largely
      depends on the type of PrP-res fragment that forms in vivo. Because the formation
      of PrP-res fragments of 7-8 kDa with ragged N and C termini is not a feature of
      Creutzfeldt-Jakob disease or fatal familial insomnia but appears to be shared by
      most GSS subtypes, it may represent a molecular marker for this disorder.

PMID- 9653186
TI  - Human autoantibodies specific for the alpha1A calcium channel subunit reduce both
      P-type and Q-type calcium currents in cerebellar neurons.
AB  - The pharmacological properties of voltage-dependent calcium channel (VDCC)
      subtypes appear mainly to be determined by the alpha1 pore-forming subunit but,
      whether P-and Q-type VDCCs are encoded by the same alpha1 gene presently is
      unresolved. To investigate this, we used IgG antibodies to presynaptic VDCCs at
      motor nerve terminals that underlie muscle weakness in the autoimmune Lambert
      Eaton myasthenic syndrome (LEMS). We first studied their action on changes in
      intracellular free Ca2+ concentration [Ca2+]i in human embryonic kidney (HEK293)
      cell lines expressing different combinations of human recombinant VDCC subunits.
      Incubation for 18 h with LEMS IgG (2 mg/ml) caused a significant dose-dependent
      reduction in the K+-stimulated [Ca2+]i increase in the alpha1A cell line but not
      in the alpha1B, alpha1C, alpha1D, and alpha1E cell lines, establishing the
      alpha1A subunit as the target for these autoantibodies. Exploiting this
      specificity, we incubated cultured rat cerebellar neurones with LEMS IgG and
      observed a reduction in P-type current in Purkinje cells and both P- and Q-type
      currents in granule cells. These data are consistent with the hypothesis that the
      alpha1A gene encodes for the pore-forming subunit of both P-type and Q-type
      VDCCs.

PMID- 9653187
TI  - Representation of spatial frequency and orientation in the visual cortex.
AB  - Knowledge of the response of the primary visual cortex to the various spatial
      frequencies and orientations in the visual scene should help us understand the
      principles by which the brain recognizes patterns. Current information about the
      cortical layout of spatial frequency response is still incomplete because of
      difficulties in recording and interpreting adequate data. Here, we report results
      from a study of the cat primary visual cortex in which we employed a new image
      analysis method that allows improved separation of signal from noise and that we
      used to examine the neurooptical response of the primary visual cortex to
      drifting sine gratings over a range of orientations and spatial frequencies. We
      found that (i) the optical responses to all orientations and spatial frequencies
      were well approximated by weighted sums of only two pairs of basis pictures, one
      pair for orientation and a different pair for spatial frequency; (ii) the
      weightings of the two pictures in each pair were approximately in quadrature (1/4
      cycle apart); and (iii) our spatial frequency data revealed a cortical map that
      continuously assigns different optimal spatial frequency responses to different
      cortical locations over the entire spatial frequency range.

PMID- 9653188
TI  - Sequestration of cAMP response element-binding proteins by transcription factor
      decoys causes collateral elaboration of regenerating Aplysia motor neuron axons.
AB  - Axonal injury increases intracellular Ca2+ and cAMP and has been shown to induce
      gene expression, which is thought to be a key event for regeneration. Increases
      in intracellular Ca2+ and/or cAMP can alter gene expression via activation of a
      family of transcription factors that bind to and modulate the expression of CRE
      (Ca2+/cAMP response element) sequence-containing genes. We have used Aplysia
      motor neurons to examine the role of CRE-binding proteins in axonal regeneration
      after injury. We report that axonal injury increases the binding of proteins to a
      CRE sequence-containing probe. In addition, Western blot analysis revealed that
      the level of ApCREB2, a CRE sequence-binding repressor, was enhanced as a result
      of axonal injury. The sequestration of CRE-binding proteins by microinjection of
      CRE sequence-containing plasmids enhanced axon collateral formation (both number
      and length) as compared with control plasmid injections. These findings show that
      Ca2+/cAMP-mediated gene expression via CRE-binding transcription factors
      participates in the regeneration of motor neuron axons.

PMID- 9653189
TI  - Synaptic facilitation by reflected action potentials: enhancement of transmission
      when nerve impulses reverse direction at axon branch points.
AB  - A rapid, reversible enhancement of synaptic transmission from a sensory neuron is
      reported and explained by impulses that reverse direction, or reflect, at axon
      branch points. In leech mechanosensory neurons, where one can detect reflection
      because it is possible simultaneously to study electrical activity in separate
      branches, action potentials reflected from branch points within the central
      nervous system under physiological conditions. Synapses adjacent to these branch
      points were activated twice in rapid succession, first by an impulse arriving
      from the periphery and then by its reflection. This fast double-firing
      facilitated synaptic transmission, increasing it to more than twice its normal
      level. Reflection occurred within a range of resting membrane potentials, and
      electrical activity produced by mechanical stimulation changed membrane potential
      so as to produce and cease reflection. A compartmental model was used to
      investigate how branch-point morphology and electrical activity contribute to
      produce reflection. The model shows that mechanisms that hyperpolarize the
      membrane so as to impair action potential propagation can increase the range of
      structures that can produce reflection. This suggests that reflection is more
      likely to occur in other structures where impulses fail, such as in axons and
      dendrites in the mammalian brain. In leech sensory neurons, reflection increased
      transmission from central synapses only in those axon branches that innervate the
      edges of the receptive field in the skin, thereby sharpening spatial contrast.
      Reflection thus allows a neuron to amplify synaptic transmission from a selected
      group of its branches in a way that can be regulated by electrical activity.

PMID- 9653190
TI  - Neurabin is a synaptic protein linking p70 S6 kinase and the neuronal
      cytoskeleton.
AB  - p70 S6 kinase (p70(S6k)) is a mitogen-activated protein kinase that plays a
      central role in the control of mRNA translation. It physiologically
      phosphorylates the S6 protein of the 40s ribosomal subunit in response to
      mitogenic stimuli and is a downstream component of the rapamycin-sensitive
      pathway, which includes the 12-kDa FK506 binding protein and includes rapamycin
      and the 12-kDa FK506 binding protein target 1. Here, we report the identification
      of neurabin (neural tissue-specific F-actin binding protein), a neuronally
      enriched protein of 1,095 amino acids that contains a PDZ domain and binds
      p70(S6k). We demonstrate the neurabin-p70(S6k) interaction by yeast two-hybrid
      analysis and biochemical techniques. p70(S6k) and neurabin coimmunoprecipitate
      from transfected HEK293 cells. Site-directed mutagenesis of neurabin implicates
      its PDZ domain in the interaction with p70(S6k), and deletion of the carboxyl
      terminal five amino acids of p70(S6k) abrogates the interaction. Cotransfection
      of neurabin in HEK293 cells activates p70(S6k) kinase activity. The mRNA of
      neurabin and p70(S6k) show striking colocalization in brain sections by in situ
      hybridization. Subcellular fractionation of rat brain demonstrates that neurabin
      and p70(S6k) both localize to the soluble fraction of synaptosomes. By way of its
      PDZ domain, the neuronal-specific neurabin may target p70(S6k) to nerve
      terminals.

PMID- 9653191
TI  - Normal retina releases a diffusible factor stimulating cone survival in the
      retinal degeneration mouse.
AB  - The role of cellular interactions in the mechanism of secondary cone
      photoreceptor degeneration in inherited retinal degenerations in which the
      mutation specifically affects rod photoreceptors was studied. We developed an
      organ culture model of whole retinas from 5-week-old mice carrying the retinal
      degeneration mutation, which at this age contain few remaining rods and numerous
      surviving cones cocultured with primary cultures of mixed cells from postnatal
      day 8 normal-sighted mice (C57BL/6) retinas or retinal explants from normal
      (C57BL/6) or dystrophic (C3H/He) 5-week-old mice. After 7 days, the numbers of
      residual cone photoreceptors were quantified after specific peanut lectin or anti
      arrestin antibody labeling by using an unbiased stereological approach.
      Examination of organ cultured retinas revealed significantly greater numbers of
      surviving cones (15-20%) if cultured in the presence of retinas containing normal
      rods as compared with controls or cocultures with rod-deprived retinas. These
      data indicate the existence of a diffusible trophic factor released from retinas
      containing rod cells and acting on retinas in which only cones are present.
      Because cones are responsible for high acuity and color vision, such data could
      have important implications not only for eventual therapeutic approaches to human
      retinal degenerations but also to define interactions between retinal
      photoreceptor types.

PMID- 9653192
TI  - Lithium acutely inhibits and chronically up-regulates and stabilizes glutamate
      uptake by presynaptic nerve endings in mouse cerebral cortex.
AB  - We previously reported that lithium stimulated extracellular glutamate
      accumulation in monkey and mouse cerebrocortical slices. We report here that this
      is caused by lithium-induced inhibition of glutamate uptake into the slice.
      Glutamate release was amplified 5-fold over inhibition of uptake. When the
      effects of lithium and the specific glutamate transporter inhibitors, L-trans
      pyrrolidine-2, 4-dicarboxylic acid and dihydrokainic acid, were plotted as
      glutamate accumulation vs. inhibition of glutamate uptake, the plots were
      superimposable. This finding strongly indicates that lithium-induced glutamate
      accumulation is caused entirely by inhibition of uptake. With cerebrocortical
      synaptosomes, inhibition of glutamate uptake was greater than in slices,
      suggesting that presynaptic nerve endings are the primary site of inhibition of
      uptake by lithium. Inhibition of uptake was caused by a progressive lowering of
      Vmax, as the lithium concentration was increased, whereas the Km remained
      constant, indicating that lithium inhibited the capacity of the transporter but
      not its affinity. Chronic treatment of mice with lithium, achieving a blood level
      of 0.7 mM, which is on the low side of therapeutic, up-regulated synaptosomal
      uptake of glutamate. This would be expected to exert an antimanic effect. Lithium
      is a mood stabilizer, dampening both the manic and depressive phases of bipolar
      disorder. Interestingly, although the uptake of glutamate varied widely in
      individual control mice, uptake in lithium-treated mice was stabilized over a
      narrow range (variance in controls, 0.423; in lithium treated, 0.184).

PMID- 9653193
TI  - Reversal of anticancer multidrug resistance by the ardeemins.
AB  - Two "reverse prenyl" hexahydropyrroloindole alkaloids, 5-N-acetylardeemin and 5-N
      acetyl-8-demethylardeemin, were evaluated as reversal agents in cells exhibiting
      a multidrug resistant (MDR) phenotype. These ardeemins (i) reversed drug
      resistance to vinblastine (VBL) or to taxol as much as 700-fold at relatively
      noncytotoxic concentrations in vitro; (ii) as a single agent at high
      concentrations killed MDR cells more efficaciously than the respective parent
      wild-type cells; and (iii) exhibited strong synergistic effects with doxorubicin
      (DX) and VBL against the growth of MDR neoplastic cells, and to a lesser extent,
      of the parent wild-type cells. Mechanistic studies showed that photoaffinity
      labeling of P-glycoprotein (Pgp) with [3H] azidopine was competitively inhibited
      by the ardeemins. Resistance to DX in MDR-[Pgp+ and MDR-associated protein
      (MRP)+], MDR-Pgp+, lung resistance protein (LRP)+-expressing, and wild-type lung
      cancer cells were reversed 110- to 200-fold, 50- to 66-fold, 7- to 15-fold, and
      0.9- to 3-fold, respectively, by 20 microM of the ardeemins. Moreover, these
      compounds increased the intracellular accumulation of VBL and markedly decreased
      its efflux. Finally, in vivo combination studies demonstrated that nontoxic doses
      of the ardeemins with DX significantly improved the chemotherapeutic effects in
      B6D2F1 mice bearing DX-resistant P388 leukemia, and nude mice bearing human MX-1
      mammary carcinoma xenografts. The above features indicate that the ardeemins may
      have utility in the therapy of cancer.

PMID- 9653194
TI  - The endogenous cannabinoid anandamide inhibits human breast cancer cell
      proliferation.
AB  - Anandamide was the first brain metabolite shown to act as a ligand of "central"
      CB1 cannabinoid receptors. Here we report that the endogenous cannabinoid
      potently and selectively inhibits the proliferation of human breast cancer cells
      in vitro. Anandamide dose-dependently inhibited the proliferation of MCF-7 and
      EFM-19 cells with IC50 values between 0.5 and 1.5 microM and 83-92% maximal
      inhibition at 5-10 microM. The proliferation of several other nonmammary tumoral
      cell lines was not affected by 10 microM anandamide. The anti-proliferative
      effect of anandamide was not due to toxicity or to apoptosis of cells but was
      accompanied by a reduction of cells in the S phase of the cell cycle. A stable
      analogue of anandamide (R)-methanandamide, another endogenous cannabinoid, 2
      arachidonoylglycerol, and the synthetic cannabinoid HU-210 also inhibited EFM-19
      cell proliferation, whereas arachidonic acid was much less effective. These
      cannabimimetic substances displaced the binding of the selective cannabinoid
      agonist [3H]CP 55, 940 to EFM-19 membranes with an order of potency identical to
      that observed for the inhibition of EFM-19 cell proliferation. Moreover,
      anandamide cytostatic effect was inhibited by the selective CB1 receptor
      antagonist SR 141716A. Cell proliferation was arrested by a prolactin mAb and
      enhanced by exogenous human prolactin, whose mitogenic action was reverted by
      very low (0.1-0.5 microM) doses of anandamide. Anandamide suppressed the levels
      of the long form of the prolactin receptor in both EFM-19 and MCF-7 cells, as
      well as a typical prolactin-induced response, i.e., the expression of the breast
      cancer cell susceptibility gene brca1. These data suggest that anandamide blocks
      human breast cancer cell proliferation through CB1-like receptor-mediated
      inhibition of endogenous prolactin action at the level of prolactin receptor.

PMID- 9653195
TI  - Novel paracrine signaling mechanism in the ocular ciliary epithelium.
AB  - The ciliary body contains an epithelial bilayer consisting of an outer pigmented
      cell layer (PE) and an inner nonpigmented cell layer (NPE) responsible for
      aqueous humor secretion. Secretion may be mediated in part by cytosolic Ca2+
      concentration ([Ca2+]i), but whether or how the two layers could coordinate their
      Ca2+ signals to regulate secretion is unclear. To investigate interactions
      between PE and NPE, we examined [Ca2+]i signaling in isolated intact ciliary
      epithelial bilayers using confocal microscopy. Phenylephrine selectively
      increased [Ca2+]i in PE and acetylcholine increased [Ca2+]i in NPE, but
      epinephrine increased [Ca2+]i in both layers. This increase spread from PE to
      NPE, and [Ca2+]i signaling across the bilayer remained coordinated during [Ca2+]i
      oscillations. All epinephrine-induced [Ca2+]i signaling was blocked by the alpha1
      adrenergic antagonist prazosin, whereas signaling in the NPE but not PE was
      blocked by the beta-adrenergic antagonist propranolol, the gap junction blockers
      octanol and 18alpha-glycyrrhetinic acid, or the A kinase inhibitor Rp
      diastereomer of adenosine 3',5'-cyclic monophosphothioate. The beta-adrenergic
      agonist isoproterenol failed to increase Ca2+ by itself, but isoproterenol plus
      phenylephrine-induced [Ca2+]i signals across the bilayer similar to those induced
      by epinephrine. Finally, isoproterenol increased cell-to-cell spread of lucifer
      yellow via gap junctions, whereas cell-to-cell spread of [Ca2+]i signals could be
      induced by photorelease of caged inositol 1,4,5-trisphosphate. Thus, calcium
      signals are coordinated in the epithelial bilayer so that adrenergic stimulation
      can increase [Ca2+]i in NPE, but only if NPE are primed by activation of
      endogenous adenylyl cyclase, whereupon they receive stimulation from adjacent PE
      via gap junctions. This novel interplay between endocrine and paracrine pathways
      may coordinate [Ca2+]i signaling across the ciliary epithelial bilayer.

PMID- 9653196
TI  - Human alpha-endosulfine, a possible regulator of sulfonylurea-sensitive KATP
      channel: molecular cloning, expression and biological properties.
AB  - Sulfonylureas are a class of drugs commonly used in the management of non-insulin
      dependent diabetes mellitus. Their therapeutic action results primarily from
      their ability to inhibit ATP-sensitive potassium (KATP) channels in the plasma
      membrane of pancreatic beta cells and thereby stimulate insulin release. A key
      question is whether an endogenous ligand for the KATP channel exists that is able
      to mimic the inhibitory effects of sulfonylureas. We describe here the cloning of
      the cDNA encoding human alpha-endosulfine, a 13-kDa peptide that is a putative
      candidate for such a role. alpha-Endosulfine is expressed in a wide range of
      tissues including muscle, brain, and endocrine tissues. The recombinant protein
      displaces binding of the sulfonylurea [3H]glibenclamide to beta cell membranes,
      inhibits cloned KATP channel currents, and stimulates insulin secretion. We
      propose that endosulfine is an endogenous regulator of the KATP channel, which
      has a key role in the control of insulin release and, more generally, couples
      cell metabolism to electrical activity.

PMID- 9653197
TI  - Low-temperature carbon utilization is regulated by novel gene activity in the
      heart of a hibernating mammal.
AB  - Hibernation is a physiological adaptation characterized by dramatic decreases in
      heart rate, body temperature, and metabolism, resulting in long-term dormancy.
      Hibernating mammals survive for periods up to 6 mo in the absence of food by
      minimizing carbohydrate catabolism and using triglyceride stores as their primary
      source of fuel. The cellular and molecular mechanisms underlying the changes from
      a state of activity to the hibernating state are poorly understood; however, the
      selective expression of genes offers one level of control. To address this
      problem, we used a differential gene expression screen to identify genes that are
      responsible for the physiological characteristics of hibernation in the heart of
      the thirteen-lined ground squirrel (Spermophilus tridecemlineatus). Here, we
      report that genes for pancreatic lipase and pyruvate dehydrogenase kinase isozyme
      4 are up-regulated in the heart during hibernation. Pancreatic lipase is normally
      expressed exclusively in the pancreas, but when expressed in the hibernating
      heart it liberates fatty acids from triglycerides at temperatures as low as 0
      degreesC. Pyruvate dehydrogenase kinase isozyme 4 inhibits carbohydrate oxidation
      and depresses metabolism by preventing the conversion of pyruvate to Ac-CoA. The
      resulting anaerobic glycolysis and low-temperature lipid catabolism provide
      evidence that adaptive changes in cardiac physiology are controlled by the
      differential expression of genes during hibernation.

PMID- 9653198
TI  - Local mechanical stimulation induces components of the pathogen defense response
      in parsley.
AB  - Cell suspension cultures of parsley (Petroselinum crispum) have previously been
      used as a suitable system for studies of the nonhost resistance response to
      Phytophthora sojae. In this study, we replaced the penetrating fungus by local
      mechanical stimulation by using a needle of the same diameter as a fungal hypha,
      by local application of a structurally defined fungus-derived elicitor, or by a
      combination of the two stimuli. Similar to the fungal infection hypha, the local
      mechanical stimulus alone induced the translocation of cytoplasm and nucleus to
      the site of stimulation, the generation of intracellular reactive oxygen
      intermediates (ROI), and the expression of some, but not all, elicitor-responsive
      genes. When the elicitor was applied locally to the cell surface without
      mechanical stimulation, intracellular ROI also accumulated rapidly, but
      morphological changes were not detected. A combination of the mechanical stimulus
      with simultaneous application of low doses of elicitor closely simulated early
      reactions to fungal infection, including cytoplasmic aggregation, nuclear
      migration, and ROI accumulation. By contrast, cytoplasmic rearrangements were
      impaired at high elicitor concentrations. Neither papilla formation nor
      hypersensitive cell death occurred under the conditions tested. These results
      suggest that mechanical stimulation by the invading fungus is responsible for the
      observed intracellular rearrangements and may trigger some of the previously
      demonstrated changes in the activity of elicitor-responsive genes, whereas
      chemical stimulation is required for additional biochemical processes. As yet
      unidentified signals may be involved in papilla formation and hypersensitive cell
      death.

PMID- 9653199
TI  - Glutaredoxin function for the carboxyl-terminal domain of the plant-type 5'
      adenylylsulfate reductase.
AB  - 5'-Adenylylsulfate (APS) reductase (EC 1.8.99.-) catalyzes the reduction of
      activated sulfate to sulfite in plants. The evidence presented here shows that a
      domain of the enzyme is a glutathione (GSH)-dependent reductase that functions
      similarly to the redox cofactor glutaredoxin. The APR1 cDNA encoding APS
      reductase from Arabidopsis thaliana is able to complement the cysteine auxotrophy
      of an Escherichia coli cysH [3'-phosphoadenosine-5'-phosphosulfate (PAPS)
      reductase] mutant, only if the E. coli strain produces glutathione. The purified
      recombinant enzyme (APR1p) can use GSH efficiently as a hydrogen donor in vitro,
      showing aKm[GSH] approximately of 0.6 mM. Gene dissection was used to express
      separately the regions of APR1p from amino acids 73-327 (the R domain),
      homologous with microbial PAPS reductase, and from amino acids 328-465 (the C
      domain), homologous with thioredoxin. The R and C domains alone are inactive in
      APS reduction, but the activity is partially restored by mixing the two domains.
      The C domain shows a number of activities that are typical of E. coli
      glutaredoxin rather than thioredoxin. Both the C domain and APR1p are highly
      active in GSH-dependent reduction of hydroxyethyldisulfide, cystine, and
      dehydroascorbate, showing a Km[GSH] in these assays of approximately 1 mM. The R
      domain does not show these activities. The C domain is active in GSH-dependent
      reduction of insulin disulfides and ribonucleotide reductase, whereas APR1p and R
      domain are inactive. The C domain can substitute for glutaredoxin in vivo as
      demonstrated by complementation of an E. coli mutant, underscoring the functional
      similarity between the two enzymes.

PMID- 9653200
TI  - Inhibition in verbal working memory revealed by brain activation.
AB  - There are many occasions in which humans and other animals must inhibit the
      production of some behavior or inhibit the processing of some internal
      representation. Success in inhibitory processing under normal circumstances can
      be revealed by the fact that certain brain pathologies render inhibitory
      processing ineffective. These pathologies often have been associated with damage
      to frontal cortex, including lateral and inferior aspects. We provide behavioral
      evidence of a verbal working memory task that, by hypothesis, engaged inhibitory
      processing, and we show (by using positron emission tomograpny) that the
      inhibitory processing is associated with a lateral portion of the left prefrontal
      cortex. The task in which subjects engaged was item-recognition: Four target
      letters were presented for storage followed, after a brief interval, by a probe
      letter that could match a target letter or not. On some trials, when the probe
      did not match a target letter and therefore required a "no" response, the probe
      had matched a target letter of the previous trial, so on these trials a "yes"
      response was prepotent and had to be inhibited, by hypothesis. Compared with a
      condition in which no prepotent response was created, this condition yielded
      brain activation in left inferior frontal gyrus, in the region of Brodmann's area
      45.

PMID- 9653201
TI  - Health promoting lifestyles: healthy women and women with breast cancer.

PMID- 9653202
TI  - Teaching ethics in nursing.

PMID- 9653203
TI  - Telehealth in home care practice.

PMID- 9653204
TI  - A creative student presentation on the nursing management of a complex family.

PMID- 9653205
TI  - Chest tubes: to clamp or not to clamp.

PMID- 9653206
TI  - Teach what?: reflections on the transition from hospital teaching to teaching in
      the community.
AB  - For a nurse educator, the sudden assignment to teaching in the community after
      years of hospital teaching and practice can cause distress. While persons with
      such experience do not possess the skills to teach the care of aggregate
      populations, they can be successful in teaching students to care for patients in
      their homes and in other community settings. Participating in on-site
      orientation, developing perspectives that recognize patient autonomy and the
      significance of family context, and using more discovery learning strategies
      enable faculty to achieve course goals and to contribute to curricular goals.

PMID- 9653207
TI  - Stress, balloons, and theory.

PMID- 9653208
TI  - Nursing students and Haiku.
AB  - The emphasis in nursing education is frequently on facts, details, and linear
      issues. Students need more encouragement to use the creative abilities which
      exist in each of them. The use of haiku, a simple unrhymed Japanese verse, is one
      method which stimulates nursing students to use their creativity. A haiku
      exercise worked well in encouraging a group of nursing students to express their
      feelings.

PMID- 9653209
TI  - Strengthening the interdisciplinary education of nurses in violence prevention,
      detection, and intervention.

PMID- 9653210
TI  - Teaching pathophysiology from a multicultural perspective.
AB  - Pathophysiology is the study of deviation from normal physiology and the 70
      kilogram white male that remains the standard by which all else is compared. As
      United States demographics shift, a new perspective is necessary to meet the
      needs of multicultural patients. This article describes how a multicultural
      perspective provides a new framework for teaching that both transforms course
      content and stimulates new teaching methodologies.

PMID- 9653211
TI  - Refinements in the dimensional analysis method of dose calculation problem
      solving.
AB  - Although the dimensional analysis method for solving dose calculation problems is
      gaining acceptance with nurse educators, many inconsistencies in teaching
      methodologies remain that can be confusing to both students and practicing
      nurses. The author presents refinements to the dimensional analysis method which
      can improve speed and accuracy in dose calculations and will be universally
      applicable to all types of clinical dosage problems.

PMID- 9653212
TI  - A collaborative preceptor model for clinical teaching of beginning nursing
      students.
AB  - With decreased clinical and faculty resources, monitoring students in the
      clinical area for safety and progress can be difficult. The authors discuss a
      project that used preceptors for selected beginning students to address issues
      related to high student-to-faculty ratios, individualized teaching, role
      modeling, and increased faculty time for scholarship. Based on student evaluation
      of the pilot project, the authors recommend using nurse preceptors for teaching
      beginning nursing students.

PMID- 9653213
TI  - Boyer's model of scholarship applied to a career ladder for nontenured nursing
      faculty.
AB  - This article presents a career ladder for the reappointment and promotion of
      nontenured clinical faculty, based on Boyer's model of the scholarship of
      teaching, application, discovery, and integration and on his four principles and
      six standards. Titles, lengths of appointments, criteria, obligations, and
      professional development are defined for four levels of clinical faculty. Guide
      questions modeled on Boyer's dimensions of scholarship, principles, and standards
      that were used to guide the development of the career ladder are included.

PMID- 9653214
TI  - Curriculum restructuring using the practice-based Omaha System.
AB  - Nursing programs across the country are reviewing and revising their curricula in
      search of the best ways to prepare nursing students for clinical practice in the
      21st century. Because of compatibility with healthcare trends, program
      philosophy, and university functions, one baccalaureate program chose to organize
      curricular content using the structure of the practice-based Omaha System. The
      authors share the experiences of this process.

PMID- 9653215
TI  - Designing courses for the Internet. A conceptual approach.
AB  - One current higher education paradigm shift is the movement from traditional
      classroom settings and interactive television satellite transmission to course
      and program delivery via the World Wide Web (WWW). The authors describe the
      experiences of faculty in reconceptualizing and redesigning course and program
      delivery via the Internet. An electronic "template" has been collaboratively
      developed by multidisciplinary university partners to facilitate this work. The
      template incorporates an advanced nursing practice conceptual framework based on
      American Association of Colleges of Nursing (AACN) core educational essentials
      for advanced practice combined with a continuum of electronic course tools.
      Strategies, tools, and applications are discussed.

PMID- 9653217
TI  - Ethical problems in research on families who are abusing children.
AB  - Child abuse within the family is a highly sensitive issue and therefore difficult
      to research. This article is based on our experiences of a child abuse research
      project in Finland. Special attention is given to ethical considerations during
      the initiation of the study, and in the sampling procedures, data collection and
      reporting. Most importantly, all those taking part in studies on sensitive issues
      must be guaranteed full confidentiality and anonymity. There are also other
      ethical considerations that go beyond the usual concerns in the research process.

PMID- 9653216
TI  - The legal and ethical status of children in health care in the UK.
AB  - Ethical issues about children's rights in respect of matters concerning resource
      allocation or treatment opportunities are now a matter for public consumption and
      concern. Alongside this exists a long-frustrated desire by children's nurses to
      promote children's health. Long-held assumptions about the legal and moral status
      of children within the health care system in this country are now rightly
      scrutinized and challenged. Those of us who claim to represent children now
      possess an opportunity to exploit public attention for the benefit of these
      children. This article will explore selected major relevant legal and moral
      concepts that relate to children with the aim of making transparent some of the
      important and often confusing information available. It is anticipated that
      debates about the legal and ethical status of children may be stimulated and
      fuelled from the following discussion. It is strongly recommended that entering
      into dialogue with families and children about their perceived needs will go a
      long way towards advancing thoughtful nursing care of individual children, their
      families and the general population.

PMID- 9653218
TI  - Ethical issues for neonatal nurses.
AB  - This article examines the involvement of neonatal nurses in ethical issues,
      achieved through a survey of Australian neonatal nurses. The aim was to discover
      if nurses were involved in ethical decisions, to examine various categories of
      neonates and the concerns that nurses felt about them, and to determine the
      extent to which nurses saw themselves as advocates. A response rate of 65% was
      achieved from nurses in two states who worked in intensive care and special care
      nurseries. The findings show that nurses were more likely to be involved in
      clinical decision making than in ethical decision making, showed the greatest
      concern for infants who had an uncertain prognosis, and saw themselves as
      advocates for their patients. The issues surrounding these findings are examined.

PMID- 9653219
TI  - Nurses' attitudes towards developing a do not resuscitate policy in Japan.
AB  - Two questionnaire surveys are reported describing the attitudes of 127 Japanese
      nurses towards developing a do not resuscitate (DNR) policy. The background
      information features the Japanese health care situations: a lack of policies for
      end-of-life care decisions; frequent life-prolonging treatments initiated without
      the patient's knowledge or consent; ethical dilemmas confronting nurses in
      relation to such treatments; and the public's growing concern over end-of-life
      care. A hypothetical DNR policy was used in which a health professional asked
      patients about their decision regarding DNR. The respondents supported this model
      DNR policy as an ideal. However, they noted that this policy was at variance with
      Japanese culture. Recommendations for Japanese nurses emerged from the data. In
      order to make an impact on end-of-life decision making, nurses should take
      culturally appropriate actions: (1) teach patients about their rights; and (2)
      work with physicians to provide patients with accurate information about their
      condition.

PMID- 9653220
TI  - Ethics in health care management: developing an instrument to assess humane
      caring.
AB  - The care of patients should be professional, human and humane. This is an ethical
      issue. The words human (inhimillinen) and humane (ihmislaheinen) have different
      meanings in the Finnish language. At Kuopio University Hospital (1200 beds), in
      Finland, it was decided to provide patients with professional and humane caring.
      Ethical values differ for different groups of people. Therefore humane caring was
      assessed by questioning both hospital patients (n = 160) and staff (n = 196). The
      data were subjected to content analysis. The result was that the values obtained
      for both patients and staff were similar. Five descriptive categories of humane
      caring emerged. To discover what kind of caring was provided for patients, the
      categories were operationalized into 66 criteria and a questionnaire was drawn up
      on the basis of these criteria. The data for evaluation of the quality of caring
      were collected from patients (n = 1708). The data were analysed using cross
      tabulations and the chi-squared test; sum variables were calculated for the five
      standards. The results suggest that special attention should be paid to
      vulnerable patient groups (e.g. the elderly and the young). One means of ethical
      management is to support our staff to care more humanely by discussing with them
      the results of this study, setting standards and criteria for humane caring and
      what this means in practice. It is hoped our caring will therefore be more
      humane.

PMID- 9653221
TI  - Challenges to nursing values in a changing nursing environment.
AB  - The aim of this paper is to analyse how the broad context of nursing practice
      plays a stimulating and/or a restricting role in the process of ethical caring.
      Three areas of special attention are noted. First, on the societal level, some
      developments that influence the state of affairs in the caring sector are
      indicated. Secondly, concerning the nursing and medical professions, an
      interprofessional dialogue based on specific competence is outlined. Thirdly,
      there is a discussion of how health care institutions can evolve from a business
      undertaking to a pedagogic-moral area where nurses can learn the moral attitudes
      that are essential to achieve 'good care'

PMID- 9653222
TI  - Practical dignity in caring.
AB  - It is difficult to understand the meaning of 'dignity' in human rights, bioethics
      and nursing literature because the word is used so vaguely. Unless dignity's
      meaning is spelt out it can disappear beneath more tangible priorities. In this
      article we define dignity and show how this can help health workers to maintain
      the dignity of people in their care.

PMID- 9653223
TI  - A charter for ethical research in maternity care: Association for Improvements in
      the Maternity Services; the National Childbirth Trust.

PMID- 9653224
TI  - Over the past decade RCN Congress has been marked down in government circles as
      an event worth avoiding.

PMID- 9653225
TI  - US nurses take a stand. In California and New York nurses have taken strike
      action against attempts to erode their pay and conditions.

PMID- 9653226
TI  - Staying the course. Figures on drop out rates for students and non-registration
      after qualification have set alarm bells ringing.

PMID- 9653227
TI  - Life at the top. June Girvin's survey examining the experiences of nurse
      executives provides a fascinating insight into their thoughts and views.

PMID- 9653228
TI  - Prizing equality. Nurses are being encouraged to enter the new NHS Equality
      Awards, which aim to reward practice that stops discrimination in the health
      service.

PMID- 9653229
TI  - In praise of older staff.

PMID- 9653230
TI  - Making decisions for patients.

PMID- 9653231
TI  - Bully tactics. How can trust bosses combat bullying?

PMID- 9653232
TI  - Dress code. Susie Pilling says nurses should lobby for a research--based wound
      care pack.

PMID- 9653234
TI  - Ringing the changes.

PMID- 9653235
TI  - Understanding the language of Parkinson's disease.

PMID- 9653233
TI  - Multiskilling: here to stay.

PMID- 9653236
TI  - Developing evidence--based care in mental health nursing.
AB  - For evidence-based practice to become a reality, its effects must be demonstrated
      clearly in the clinical situation. Practitioners must be sen to access, evaluate
      and apply research-based evidence in their day-to-day work. In this article, the
      author considers how this process could work in mental health nursing.

PMID- 9653237
TI  - Treatment of patients with haemochromatosis.

PMID- 9653238
TI  - Expanding the nursing profession.
AB  - this paper explores the political, economic and demographic developments which
      are shaping new nursing practices throughout the world. The authors observe that
      these developments are generally seen to challenge traditional models of nursing
      and encourage the role of sub-professional support workers.

PMID- 9653239
TI  - Assessing and controlling risk.
AB  - This article describes the principles of risk assessment in the workplace. It
      outlines regulations relating to health and safety at work as they affect
      nursing, and goes on to discuss both qualitative and quantitative risk
      assessment.

PMID- 9653240
TI  - A stranger in your body.

PMID- 9653241
TI  - Psychiatric nurses need to face up to the reality of their role.

PMID- 9653242
TI  - A chance to make your mark.

PMID- 9653243
TI  - Wheelchair users are getting a poor deal.

PMID- 9653244
TI  - Nationalism has become a dirty word in the U.K.

PMID- 9653245
TI  - Hit squads and chimps?

PMID- 9653246
TI  - Changing the face of mental illness.

PMID- 9653247
TI  - More nurses, more patients, more work.

PMID- 9653248
TI  - All for one.

PMID- 9653249
TI  - Male Catheterisation--1.

PMID- 9653250
TI  - Workplace well-being.

PMID- 9653251
TI  - Scottish solutions.

PMID- 9653253
TI  - Courting danger.

PMID- 9653252
TI  - Baby talk.

PMID- 9653254
TI  - Practice nurses do not practise their skills, they use them to the full for the
      good of their patients.

PMID- 9653255
TI  - Switching the management of epilepsy to primary care.

PMID- 9653256
TI  - Solution-focused therapies.
AB  - This is the final part of the psychotherapy series, which has offered an overview
      and insight into some of the major talking therapies used by nurses. This series
      and extended material is being drawn together by Nursing Times and Phil Barker
      for a book on talking therapies. Previous topics covered in the series were:
      Psychodynamic psychotherapy, January 14 Humanistic therapies, February 11
      Behavioural therapies, March 11 Family and systemic therapies, April 8.

PMID- 9653257
TI  - Cleaning up the act.

PMID- 9653259
TI  - The missing link.

PMID- 9653258
TI  - Cough control.

PMID- 9653260
TI  - The inside track.

PMID- 9653261
TI  - [Annenheim is different].

PMID- 9653262
TI  - ["Friendly hospital"--Korneuburg].

PMID- 9653263
TI  - [AIDS units: ghetto or open unit for everyone?].

PMID- 9653264
TI  - [Highly active antiretroviral therapy (HAART)].

PMID- 9653265
TI  - [Austrian Nursing Society, Salzburg: shortfalls in old age homes are being played
      down].

PMID- 9653266
TI  - [Professional and relevant points. The professional association as the voice of
      health personnel is dealing with the various demands of its members...].

PMID- 9653268
TI  - [The fear of infection--myths and facts].

PMID- 9653269
TI  - [Psychosocial care of the HIV-positive patient].

PMID- 9653270
TI  - [HIV nursing without fear].

PMID- 9653271
TI  - The benefits of getting published.

PMID- 9653272
TI  - The nasogastric route.

PMID- 9653273
TI  - Taking diabetes seriously.

PMID- 9653274
TI  - Publishing your work in nursing journals.
AB  - Nurses must share their research and experiences with colleagues in order that
      areas of practice are debated and improved. Assessing the suitability of a piece
      of work for a journal and following simple ground rules will increase the
      likelihood of publication.

PMID- 9653275
TI  - Nasogastric drug administration.
AB  - Nurses working in one trust frequently requested advice on the preparation of
      drugs for nasogastric administration, prompting a survey of their knowledge in
      this area. As a result, guidelines were prepared to aid nurses and alert them to
      potential problems.

PMID- 9653276
TI  - Beliefs about diabetes and diabetic complications.
AB  - A study of people with non-insulin dependent diabetes found that, generally, they
      had a good understanding of its complications although over half believed they
      personally were not vulnerable. Non-diabetic subjects had limited knowledge in
      this area.

PMID- 9653277
TI  - Confidentiality.

PMID- 9653278
TI  - Rheumatoid arthritis.

PMID- 9653279
TI  - Pre-operative skin preparation.

PMID- 9653280
TI  - The tendering process for beds and mattresses.
AB  - As increasing numbers of expensive, sophisticated bed and mattress systems become
      available, more trusts are negotiating contracts for supply, maintenance and
      training. It is important that tissue viability nurses become involved in such
      decision-making.

PMID- 9653281
TI  - An information strategy for radiotherapy patients.

PMID- 9653282
TI  - Fatigue in patients receiving radiotherapy.
AB  - The fatigue that may accompany or follow radiotherapy is often overlooked by
      health-care staff, yet this side-effect of treatment can cause great distress.
      More research into the causes and methods of relieving such symptoms is needed.

PMID- 9653283
TI  - Intravascular catheters.
AB  - Intravascular catheters are widely used in health care for a range of therapeutic
      and diagnostic procedures involving the cardiovascular system. Nurses should be
      aware of the different types available and the problems that can arise.

PMID- 9653284
TI  - Crossing area and staff boundaries in wound care.
AB  - Staff working in hospitals, the community and nursing homes in the Fife area now
      meet in a forum to share their knowledge of wound care. The group is
      multidisciplinary and members bring experience from a variety of backgrounds.

PMID- 9653286
TI  - Community nursing.

PMID- 9653287
TI  - District nurses in the spotlight.

PMID- 9653288
TI  - Pressure sores in the community.

PMID- 9653289
TI  - Handwashing and infection.

PMID- 9653290
TI  - Patients' views of the care given by district nurses.
AB  - Understanding the actions that make patients feel 'cared for' by district nurses
      can help staff tailor their work to meet patients' needs. Patients in one study
      felt that a trusting nurse/patient relationship is the basis of good nursing.

PMID- 9653291
TI  - Disinfection of latex gloves with ethyl alcohol.
AB  - The ability to disinfect latex gloves successfully between procedures would save
      time and be cost-effective. An in vitro study examined the efficacy of using an
      ethyl alcohol/bactericide compound to disinfect latex gloves contaminated with
      five common bacteria.

PMID- 9653292
TI  - Advanced airway management.

PMID- 9653293
TI  - Pressure sore prevalence in the community.
AB  - As increasing numbers of patients are now being nursed in the community it is
      important that strategies for the prevention of pressures sores are in place. A
      prevalence survey in one trust helped staff to assess their resource needs and
      plan care.

PMID- 9653294
TI  - High temperature.

PMID- 9653295
TI  - Physiological ageing: 1.

PMID- 9653296
TI  - Evaluation of a urine chemistry analyser.
AB  - Using an automated urine analyser in the ward may improve the accuracy of urine
      testing as nurses no longer have to rely on making subjective colour comparisons.
      Staff in one urology unit tested an analyser for ease of use, convenience and
      practicality.

PMID- 9653297
TI  - Access to records.

PMID- 9653298
TI  - Urinary catheters for intermittent use.
AB  - Intermittent catheterisation is suitable for a range of patients and has a high
      level of patient satisfaction. Careful education is required to minimise the risk
      of complications and nurses should be aware of the various types of catheter
      available.

PMID- 9653299
TI  - Venous leg ulcers. Part 1: Aetiology.
AB  - A sound knowledge of the physiology of the venous system is necessary to
      understand how venous leg ulcers develop. The main risk factors are thrombus
      formation and venous incompetence and nurses should be alert to the signs of
      these conditions.

PMID- 9653300
TI  - [A global approach to health care: the problem of the the patient's wishes].
AB  - Doctors and nurses must take into account the patient's point of view. Therefore
      it is necessary to have a clear idea of the patient's wishes, as well as of his
      position with regard to the disease. This understanding must be integrated in the
      treatment and in the strategy of nursing.

PMID- 9653301
TI  - [The teaching of diagnostic methodology in nursing schools].
AB  - The European and international discussion on Nursing diagnosis let us be aware of
      diagnostic methodology in the nurse' work, at the different responsibility
      levels. In this article we discuss some problems and objectives related to the
      aims of teaching Nursing diagnosis at post basic university Nursing education
      level.

PMID- 9653302
TI  - [Structures for the international classification of nursing practice].
AB  - The following is a walk through the architectural principles behind the
      classification of nursing phenomena and of nursing interventions in the Alpha
      version of the International Classification for Nursing Practice. While some
      architectural principles are common to the two classifications, other principles
      are particular to one or the other classification.

PMID- 9653303
TI  - [International congress of nurses, 1997. Healthy youth for a better future].

PMID- 9653304
TI  - [How can nurses participate in the development of the International
      Classification of Nursing Practice (ICNP)].

PMID- 9653305
TI  - [Usefulness of psychometric evaluation in the care of psychiatric patients:
      evaluation of the Italian version of "Nurses Observation Scale for Inpatient
      Observation" (N.O.S.I.S)].
AB  - We carried out a validation study of the Italian version of the "Nurses'
      Observation Scale for Inpatient Evaluation" (It. v. N.O.S.I.E). The It. v.
      N.O.S.I.E. was administered to a heterogeneous department. Factor analysis
      revealed six factors underlying the scale structure (Social interest, Neatness,
      Irritability, Psychosis, Retardation, Competence): the result is similar to those
      of other previously published studies. The It. v. of N.O.S.I.E. can be considered
      a valid instrument useful for the nursing staff in the formulation of individual
      care plans for inpatients.

PMID- 9653306
TI  - [The world of health care and the directives 626/94-242/96 on safety and health
      in the workplace. Prevention of risks for workers: who cares for the
      caregivers?].
AB  - In Italy, the adoption of the EEC Directives on "Safety and hygiene" has brought
      into the health structures a revolution that may be summarized in the sentence:
      "to take care for people taking care". This kind of approach has had an impact
      also on the medicine legislation, with a shift from B. Ramazzini to L. Devoto,
      that is from workers' deseases to occupational medicine. In a first time laws
      were founded according to an insurance vision; subsequently safety prevailed; in
      a third phase safety and prevention were joined together. To day the basic
      concept is: prevention, protection and safety. The involved subjects and the
      innovative aspects of Dlgs 626/94 and Dlgs 242/96 are the cornerstones of the
      olistic vision according to which "to work for health may cause harm to health".

PMID- 9653307
TI  - [Professionalism in nursing: difference between theoretical learning and clinical
      activity].
AB  - There still seems to exist some dichotomy in nursing education between
      theoretical achievements and clinical practice, a key moment to verify applied
      knowledge and put it into practice. The aim with the present study is to compare
      activities considered professionalizing at a theoretical level with activities
      being performed during clinical practice. The instrument utilised to collect data
      was a questionnaire on nurse-professionalism using a Likert scale. The subject
      participating in the study were 3rd year nursing students from three universities
      in Rome. The results clearly shows how the theoretical preparation of nurse
      students is in contrast with clinical practice performance. The only nursing area
      where theory and practice seem to correspond is that of individualised nursing
      care, the biggest gap between theory and practice was found concerning research
      activities.

PMID- 9653308
TI  - [The nursing service at the enterprise: "Ospedale di Circolo e Fondazione Macchi"
      in Varese].
AB  - The article present the results of a project carried out by a group of four nurse
      managers of the Hospital "Ospedale di Circolo Fondazione Macchi" in Varese,
      Italy, in order to constitute the "Nursing Service". The Authors have described
      the initial situation with the traditional leading nursing roles in the Hospital
      (Nursing Officer and Director of the Nursing School) defining the objectives of
      the project. The goal of the Service has been identified, the organizational
      structure has been chosen and the different line and staff functions described.
      The conclusions inform on the current situation and work for the accreditation of
      the Service according to the mission of the Hospital managers and the announced
      changes in Lombardy health policy.

PMID- 9653309
TI  - [Diagnosis-related groups and nursing care: effects on nursing management].
AB  - The system of payment by activities, recently established in Italy, is
      introducing radical changements into the Italian Health System. This new system,
      however, shows some disadvantages that have been yet displayed in the american
      experience. It involves a range of consequences both for the work organisation
      and for the Nursing management. The present report emphasizes the risks and the
      opportunities they present for the Nursing profession.

PMID- 9653310
TI  - [Nutritional knowledge of a group of patients in continuous peritoneal dialysis].
AB  - The influence of nursing to the patient undergoing peritoneal dialysis is the
      focus of the present research report. By monitoring the patients knowledge, we
      can understand how nursing teaching influences patient's health and well being.

PMID- 9653311
TI  - [Urinary tract infections in patients with catheterization of the bladder].

PMID- 9653312
TI  - [From the National Federation of Associations of Nurses and Other Social Health
      Workers to the National Federation of Nursing Societies, Motives for a choice].

PMID- 9653313
TI  - [The world of health care and the directives 626/94-242/96 on safety and health
      in the workplace. Prevention of risks for workers. Who cares for the caregivers?
      2].
AB  - While the Manual Handling Task is an important source of risk, it is often
      disregarded by the nurse profession The data collected both in the scientific
      literature and in the research we are presenting here, agree on the belief that a
      higher degree of INFORMATION and EDUCATION--as established in the Dlg 626 94)
      would reduce the pathologies due to an erroneous manual handling and to the lack
      of mechanical facilities.

PMID- 9653314
TI  - [Thoughts on nursing, based on observations made in a Rome intensive care unit].
AB  - Nursing in an intensive care unit is probably one of the most extreme and
      demanding forms of nursing. Here, the nurse is confronted by the highly dependent
      patients and the demanding technological forms of treatment associated with them.
      The most demanding challenge for the nurse doesn't arise from the technology but
      from her dealing with the weak and defenseless party: the patient. Many nurses
      argue that their major difficulties are the result of poor working conditions,
      with poor staff to patient ratios, and the need to carry out physicians orders
      promptly and efficiently. The following article, in focusing on concepts of shame
      and authority, reflects on the nurse-patient-doctor relationship and argues that
      the challenges that confront the nurse go beyond those of the poor staff to
      patient ratio etc. and are indeed tied strongly to the behaviour patterns, and
      subsequent patterns of care, as perpetuated by the institutions and often, by the
      nurses themselves.

PMID- 9653315
TI  - [Bills for nursing legislation].

PMID- 9653317
TI  - [University diploma for pediatric nurses: comparing positions, perspectives].

PMID- 9653318
TI  - [Nestor Bereciartu, director general of the ROL editions died in Barcelona on the
      14 of April 1998] [In Process Citation]

PMID- 9653319
TI  - [Diet based on rations. Practical teaching for type II diabetics].
AB  - OBJECTIVE: Evaluate an increase in the level of theoretical and practical
      knowledge type II diabetics have about diets based on rations. DESIGN:
      Prospective Study MATERIAL AND METHODS: 13 Type II diabetics from a rural area
      between 45 and 70 years old with a glycosidic hemoglobin greater than 8%. DM
      theoretical knowledge test, validated by Campo et al. before and after the
      process. Practical exercise about the quantity of carbohydrates patients served
      themselves in their meals, before and after the process. RESULTS: Subjects tested
      showed improvement in the percentage of correctly answered questions on the
      knowledge test, whether computed by sections or globally. Subjects tested chose
      foods with a lower quantity of carbohydrates in them. CONCLUSIONS DRAWN BY THE
      PANEL OF AUTHORS: Upon completion of this educational procedure, the results were
      positive. A practical educational procedure yields more effective results than
      does a theoretical procedure in our patients and our medium. Patients
      demonstrated a greater level of satisfaction regarding their condition due to an
      increased knowledge about their disease and in particular, a better understanding
      about their diets.

PMID- 9653320
TI  - [Vitamin and mineral requirements in women].

PMID- 9653321
TI  - [Factors harmful during the course of pregnancy].
AB  - The important repercussions which teratological factors have in perinatal cases
      have made it necessary to create methods which detect congenital defects before
      birth. By reading this article, nursing professionals should acquire sufficient
      basic knowledge about teratogenesis and teratological factors so that they may
      then provide women with a correct health education about these topics during
      their peri and postconception periods.

PMID- 9653322
TI  - [Pulsating pumps in ambulatory chemotherapy].

PMID- 9653323
TI  - [Prevention of traffic accidents].
AB  - To inform nursing professionals about their role in the prevention of traffic
      accidents, a grave health-related problem, is the purpose of this article. To
      begin with, factors which can deteriorate one's capacity to drive vehicles, and
      over which nursing professionals can intervene, will be presented. These factors
      include alcohol, other drugs, medicines, individual morbidity, the factor of
      aging and the use of security devices. A special reference will be made about
      widely used medicines. Finally the role that a nurse can fulfill will be
      explained. This role can be directed to various sections of the general public,
      be of varying natures, be exercised with greater or lesser ease, and lastly can
      have more or less effect upon those to whom it is destined.

PMID- 9653324
TI  - [Nerves of the left lower extremity].

PMID- 9653325
TI  - [Risk factors of ischemic cardiopathy. Study of patients hospitalized in a
      coronary unit].
AB  - The purpose of this study is to determine the knowledge level patients
      hospitalized and diagnosed as suffering from ischemic cardiopathia have about
      their risk factors by means of an observationally, descriptively and cross
      sectionally designed study. This study was carried out in the Coronary Care Unit
      at the Vall d'Hebron General Hospital between December 1995 and March 1996. Data
      was taken from clinical reports; furthermore, patients involved in the study were
      interviewed. Among the results obtained, the following are worth special mention:
      57 patients or 47.5% knew about a HTA relationship; 97 patients or 81% knew about
      tobacco as a risk factor; 80 patients or 67% were aware of the cholesterol risk
      factor; and 58 patients or 48% had information regarding diabetes as a risk
      factor. No significant statistical differences were found among known coronary
      patients and nondiagnosed-coronary patients regarding their knowledge of risk
      factors. Only two-thirds of the study group considered it important to control
      their risk factors. Given the importance of knowledge about risk factors, perhaps
      this is the time to consider implementing a health educational program for this
      segment of the population.

PMID- 9653326
TI  - [Enterocutaneous fistula, a problem in nursing].

PMID- 9653327
TI  - [Studies on HIV patients].
AB  - This article analyzes the data obtained from a series of planned studies run over
      a two year period of time by a group of nurses while they carried out a health
      education program with HIV positive patients. This was made possible by a grant
      from FIS, Health Research and Investigation Fund. Due to the collaboration by
      professionals in the Nursing School of the University of Barcelona and the
      Bellvitge Hospital, these studies could be under-taken.

PMID- 9653328
TI  - [Massive hepatitis C virus infections among citizens of the Valencia community,
      needing surgical therapy. Primum non nocere].

PMID- 9653329
TI  - [Health habits of health professionals].
AB  - The conduct of medical professionals is an important educational point of
      reference for the many people who see and know them. Nurses and other medical
      workers are often role models in which their daily health habits may be imitated
      by their patients, family of friends. With this in mind a study, based on a
      previously published work in the United States (Health Practices of Nursing
      Students), was performed to determine, first, if the daily habits of nurses are
      indeed healthy and adequate to communicate a salubrious lifestyle; second, to see
      if this group considers themselves capable and responsible for changing those
      unsanitary habits that they do have. Results of the surveys of 125 subject nurses
      from the University of Navarra indicate that there is a great amount of
      consciousness regarding the danger of most unsanitary habits and the need to
      avoid them, although many of them remain firmly entrenched in their daily lives.
      The percentage of nurses who felt capable or responsible for changing unhealthy
      practices was low (67.5%).

PMID- 9653330
TI  - [Drug inhalation therapy. Therapy for patients with respiratory disorders].
AB  - We detected a high number of patients suffering from respiratory ailments which
      require successive hospital stays due to acute setbacks in their chronic
      respiratory ailments. The majority of these patients receive outpatient clinic
      treatment based on use of an inhaler. Given the direct relationship between the
      correct use of an inhaler and its effectiveness, we designed our project with the
      goal to discover the adroitness these patients have with an inhaler. The results
      of our study showed that 67% of the patients tested did not correctly use their
      inhaler, there by annulling or diminished the effectiveness of its use.

PMID- 9653331
TI  - [Nursing diagnosis of risks. Analysis of cost effectiveness].
AB  - BACKGROUND: Today, there is a discussion on the importance of the utilization of
      the nursing diagnosis: This makes convenient to evaluate the principal two
      existing methodological alternatives, that they are: 1) the problems
      identification, 2) the diagnoses statement of the NANDA within process nursing.
      The study is centered on the risk diagnoses. OBJECT: 1) To know which the two
      work methodologies is more effective. 2) To know if exist economic differences.
      METHODS: It is accomplished a cohorts study, in a population of user included in
      Program of Handicapped. These were studied during a year. RESULTS: In the group
      of patients without diagnoses the incidence rate was of 0.64 conversions/person
      year), in the group with diagnoses was of 0.22 (p < 0.001). The mean of visits
      after that the is made real, in the group with diagnoses was of 0.35, in the
      group without diagnoses of 1.69 (p = 0.012). DISCUSSION: The analysis cost
      efficiency of the two work methodologies is clearly more favorable for the
      methodology than states nursing diagnosis of the taxonomy of the NANDA.

PMID- 9653332
TI  - [Free radicals, antioxidants and environmental contamination].

PMID- 9653333
TI  - [National Congress of Non-conventional Medicine. Regulation of the study and
      exercise of alternative therapies has been reinstated].

PMID- 9653334
TI  - [Toledo was the scene of the II meeting of instructors of pediatric nursing. New
      lines of investigation in pediatric nursing].

PMID- 9653335
TI  - [The 1 unit for primary care of the aged was created in Santa Fe (Granada). The
      head of the unit is a nurse].

PMID- 9653336
TI  - [Cartilages of the larynx. Anterior view].

PMID- 9653337
TI  - [Scorpion stings].
AB  - This article begins by describing how Iberian Peninsula scorpion bites poison
      humans. Then the only potentially dangerous scorpion species in the peninsula is
      identified. Other types of scorpions or those which inhabit other continents are
      not included. Once identified, the author describes the characteristics and
      effects on the symptoms of this scorpion bite and how to treat and handle a
      victim, both at the moment when the victim is bitten and in hospitals.

PMID- 9653338
TI  - [Primary care of bedsores. Frequency and characteristics].
AB  - INTRODUCTION: The number of patients afflicted by bedsores under the care of a
      Primary Health Clinic is not well-known. Nevertheless, it is a pathology directly
      related to nursing care and one which causes an important loss in patient's
      quality of life; it aggravates and inhibits the cure of other health problems; it
      increases suffering and morbidity; and, at the same time, it increases nursing
      care time as well as the costs of health care. SUBJECTS AND METHODS: Under a
      widerange study carried out during the month of March, 1996, data from homecare
      patients suffering from bedsores was collected by means of a registration list
      sent to 305 Primary Health Care Clinic nurses in the province. RESULTS: The 177
      nurses who responded registered 107 patients with bedsores. 93.45% of these
      patients were older than 65. 234 bedsores were recorded. This means 2.19 findings
      per patient, 38.03% on heels and 21.79% on trochanters. 36.75% presented
      superficial necrosis and 24.36% evidenced profound necrosis. The average reading
      on the Norton Scale was 8.65 +/- 3.25 (mean +/- standard deviation).
      OBSERVATIONS: The prevalence of Primary Health Care Clinic patients suffering
      from bedsores in the province of Cacers during the period studied swings from 4
      to 6 patients for every 10,000 inhabitants and this value increases to between 22
      and 26 for every 10,000 inhabitants over 65.

PMID- 9653339
TI  - [Vitamin and mineral requirements in women (II)].

PMID- 9653340
TI  - [Self protection for nurses. Comparative study].
AB  - The nursing personnel at the C.H. Xeral-Cies participated in a study of various
      types of self-protection methods over two time spans. The hypotheses investigated
      were the following: 1. Is there a divergence in the percentage of personnel
      vaccinated against hepatitis B?, 2. Is there an increase in the level of
      knowledge about universal precautions?, and 3. Is there any improvement in self
      protection methods in the latter study? The statistical analysis used has a
      variable range of < 0.05. The results indicated significant differences in the
      percentage of personnel vaccinated against hepatitis B, in knowledge about
      universal precautions, and in the number of accidental punctures reported to the
      Preventative Medicine Service.

PMID- 9653341
TI  - [Spinal anesthesia. Repercussions on childbirth].
AB  - A study was carried out to discover the action of epidural anesthesia on pain, on
      the evolution of dilation and expulsion intervals, on the number of surgically
      assisted births, and on perinatal morbidity. Some of the most significant results
      indicated that with good techniques, pain disappears in all cases; that the
      dilating period is significantly shortened with epidural anesthesia, although
      there is an increase in instrumental-assisted childbirths. Even though epidural
      anesthesia is, as of this writing, the best method available, the ideal pain
      reduction method has yet to be discovered. Part of this study was presented
      before the National Congress of Midwives and received the "Nuk" Prize.

PMID- 9653342
TI  - ["The gardeners of the skin", a comic strip ... for the better understanding of
      burns].

PMID- 9653344
TI  - [A catheterization kit, radically transforming incontinence].

PMID- 9653343
TI  - [Burns of the palm of the hand, treated in ambulatory care].

PMID- 9653345
TI  - [Pain and the quality of life].

PMID- 9653346
TI  - [Nursing at home].

PMID- 9653347
TI  - [The Europe of home care].

PMID- 9653348
TI  - [Home care, towards new responsibilities?].

PMID- 9653349
TI  - [Hospitalization at home: an alternative to traditional hospitalization].

PMID- 9653350
TI  - [Hospitalization at home: the patient's point of view].

PMID- 9653352
TI  - [Present and future of hospitalization at home].

PMID- 9653351
TI  - [Hospitalization at home: the nurses' point of view].

PMID- 9653353
TI  - [Home hospitalization in psychiatry. Care adapted to the patient].

PMID- 9653354
TI  - [How to choose a wheelchair].

PMID- 9653355
TI  - [Home hospitalization in psychiatry: nurses' testimonies].

PMID- 9653356
TI  - [Inservice training: utopia or reality?].

PMID- 9653358
TI  - [Professional stress and wear].

PMID- 9653357
TI  - [Health in your luggage].

PMID- 9653359
TI  - [At the end of the line...].

PMID- 9653360
TI  - Management restructuring and care delivery redesign: dealing effectively with
      fear.

PMID- 9653361
TI  - Financial statement analysis: a continuation.

PMID- 9653363
TI  - Management restructuring: options and opportunities.

PMID- 9653362
TI  - Restructuring: make certain you change everything?

PMID- 9653364
TI  - Management restructuring: the process of change.
AB  - This article provides simple, direct "how to" process steps for nursing leaders
      and managers who sense the need to move toward a flattened, decentralized model
      as a nursing organizational structure, but are not certain how to get there. The
      process of organizational restructuring is fraught with difficulty, but for
      health care to be responsive to patients and staff, nurse leaders must take on
      the challenge. Principles and process steps that lead to a restructuring plan are
      outlined, as well as pitfalls to avoid.

PMID- 9653365
TI  - Navigating the barrier reef: QEE to successful restructuring.
AB  - This article chronicles the barriers encountered as a multidisciplinary
      department undertook management restructuring. Barriers that are addressed
      include lack of a sense of urgency; confusion and fear regarding the changing
      roles of both staff and managers; insufficient development of coaching skills;
      and lack of alignment of performance appraisals, outcomes, and rewards. Insights
      gained and strategies to deal with these barriers are discussed.

PMID- 9653366
TI  - Point-of-service teams: a leadership opportunity.
AB  - To welcome the transitions in management and leadership roles, a leader may
      consider developing the skills necessary to promote the success of
      interdisciplinary point-of-service teams. The author discusses factors that
      contribute to success in leading a point-of-service team. Key strategies and
      leader behaviors are addressed. A case study describing one point-of-service team
      for patient care redesign is presented and analyzed. The experience was viewed
      very positively by the leaders of the team; opportunities for further improvement
      are offered.

PMID- 9653367
TI  - Personal reflections on early learning in shared leadership.
AB  - Shared leadership involves a process as well as a structure. Two key principles
      apply to all forms of shared leadership: a commitment to true partnership and a
      decision-making structure that allows for balance of power. In this article, the
      author shares her personal experience of facilitating a shared leadership model
      for staff on a unit level and also an executive model of shared leadership. The
      executive model was implemented during a transition after a traditional nursing
      leadership position was vacated. Lessons learned in facilitating a staff shared
      leadership model and participating in an executive model are discussed and
      contrasted. Relationships, dialogue, partnership, and an understanding of
      boundaries are essential elements for successful implementation of shared
      leadership at any level.

PMID- 9653368
TI  - Values-based leadership and organizational development during restructuring.
AB  - This article highlights the importance of value-based leadership and cultural
      change, and illustrates how organizational development strategies can facilitate
      positive learning environments. This is essential during periods of rapid change,
      restructuring, and downsizing, when the quality of patient care can be at risk.
      By ensuring a values focus, and a systematic approach to the development of a
      "learning organization", nurses can be empowered to develop their clinical
      practice and to lead the redesign of healthcare systems in a more creative and
      patient-centered way.

PMID- 9653369
TI  - Seeing down the road: restructuring the work of leadership.
AB  - Understanding our own patterns of thought and interaction is one of the
      disciplines that can help nurse leaders move from a reactive and retrospective
      stance to becoming proactive. A familiar example, driving, illustrates this
      concept and applies these principles by suggesting practical ways that we can
      model the future for those we lead. We may not be able to totally control the
      obstacles along the way, but by staying fixed on the values of stewardship and
      service to our patients and staff, we can help draw the map of the future of
      health care.

PMID- 9653370
TI  - [The best gift is life].

PMID- 9653371
TI  - [Abortion].

PMID- 9653372
TI  - [Psychological effects of abortion].

PMID- 9653373
TI  - [An order of nurses? From myth to reality].

PMID- 9653374
TI  - [Poisoning with Amanita phalloides mushrooms. Nursing care].

PMID- 9653375
TI  - [Standards and principles of nursing].

PMID- 9653376
TI  - [Decline in male fertility: a fatality?].

PMID- 9653378
TI  - [The higher school of nursing of the Franciscan Missionaries].

PMID- 9653377
TI  - [Therapeutic touch].

PMID- 9653379
TI  - [From certification to accreditation].

PMID- 9653380
TI  - [An instrument for quality improvement and the evaluation of competence].

PMID- 9653381
TI  - [Stakes for nursing services].

PMID- 9653382
TI  - [From the project Nursing Care to accreditation. The search for quality. Pathway
      of action].

PMID- 9653383
TI  - [A pre-accreditation step. The University Hospital Center].

PMID- 9653384
TI  - [The National Agency for Accreditation and Health Care Evaluation].

PMID- 9653385
TI  - [The Regional Hospitalization Agency and the accreditation of health facilities].

PMID- 9653386
TI  - [What is newly politically correct].

PMID- 9653387
TI  - [Preparation for the entrance examinations for schools for paramedics].

PMID- 9653388
TI  - [Functions of the psychiatric staff nurse].

PMID- 9653389
TI  - [Open letter to the Minister of Health].

PMID- 9653390
TI  - [Towards a general mobilisation of the profession].

PMID- 9653391
TI  - [A national order of nurses: a legal bill shows the consensus of the principal
      associations].

PMID- 9653392
TI  - [The unity of the nursing profession is in danger. Interview with Christiane
      Vanderkam and Sylviane Hocher from the National Group for the mobilization in
      psychiatric nursing].

PMID- 9653393
TI  - Do large schools really supply more teachers?

PMID- 9653394
TI  - Improving the NRMP board: why not direct representation? National Resident
      Matching Program.

PMID- 9653395
TI  - Enduring strengths of academic medical centers.

PMID- 9653396
TI  - An autopsy-reporting system in an internal medicine residency program.

PMID- 9653397
TI  - Evaluating the curriculum with standardized patients.

PMID- 9653398
TI  - The need for true informed consent in pediatric teaching hospitals.

PMID- 9653399
TI  - Challenges to effective medical school leadership: perspectives of 22 current and
      former deans.
AB  - A persistent decline in the average tenure of medical school deans and a concern
      about the implications for medical school leadership led the Council of Deans of
      the Association of American Medical Colleges to commission the 1996-1997 study
      reported here. The author conducted open-ended interviews with a broad spectrum
      of 22 current and former deans, selected to achieve an appropriate distribution
      with regard to key characteristics of their schools and to assure the relevance
      of the findings to a broad range of settings. His in-depth analysis of the
      transcribed interviews, using standard qualitative techniques, was designed to
      illuminate the challenges confronting deans and suggest strategies to address
      them. The respondents consistently identified two forces in the health care
      environment that had had profound impacts on their role as deans and that
      frequently posed conflicts between the clinical and educational enterprises: a
      decline in the resources available to medical schools following an era of
      abundance, and unprecedented competition in the clinical arena. Analysis of their
      accounts of the problems they encountered in managing in this changed environment
      revealed several underlying sources: imbalance between the breadth of their
      responsibilities and their authority to manage; lack of clarity in the dean's
      mandate; inadequate institutional support for pursuing the missions of the
      school; insufficient attention to identifying requisite expertise and abilities
      for effective performance on the job as dean; and an anachronistic search
      process. The respondents offered numerous recommendations for addressing these
      problems, reflecting optimism about the prospects for purposeful change. While
      medical schools have unique features among educational institutions, the author
      concludes that the challenges that deans face and the strategies proposed for
      addressing them promise to have substantial relevance for academic leadership in
      other settings.

PMID- 9653400
TI  - Organizational, financial, and environmental factors influencing deans' tenure.
AB  - At a time when continuity of leadership in medical schools is most crucial, the
      tenures of deans continue to decrease. In the present study of factors
      influencing the tenures of 382 U.S. medical school deans from 1985 to 1994, the
      authors focused on issues that were likely to have had a greater impact on deans'
      tenures in recent years. They assumed that longer tenures are associated with
      less complex organizational factors and more stable environmental factors.
      Conversely, they assumed that deans and their tenures are adversely affected by
      an institution's declining financial health, a complex organizational structure,
      and a changing clinical marketplace where there is rapid growth of managed care.
      The authors compared the relationships between these factors and the length of
      deans' tenures during the ten-year period studied. Among the most important
      findings were the fact that schools that were less healthy financially, that had
      the same owner as the primary teaching hospital, and that had smaller numbers of
      faculty tended to have shorter dean's tenures and higher turnovers of deans.
      While the reason for shorter tenures of deans at schools that are less
      financially healthy is understandable, the effect of common ownership of the
      school and teaching hospital is less obvious, but perhaps the greater
      preoccupation of deans with the clinical enterprise in that circumstance is a
      significant constraint. The authors hope that the insights from their findings
      will be useful to future candidates for deanships in their negotiations with
      university officials and will help all parties reach more explicit agreements on
      such issues as expectations for financial performance of the medical school and
      the roles and relationships of the dean and the teaching hospital director.

PMID- 9653401
TI  - The dean as spiritual leader.
AB  - These are hard times for medical school deans--high turnover among deans, the
      fiscal distress of many medical schools, the gap between what deans expect the
      job will be and what is required of them, the stark differences between what the
      job of dean is today and what it was in the past, and the threats to the academic
      missions of education and research. Using stories, anecdotes, and parables, the
      authors illustrates how these very difficulties might be an opportunity to
      rethink the role of deans and to re-examine the attributes and skills required of
      successful deans today. The ultimate goals of medical education have not changed,
      but the drastic nature of the changes taking place all around, and within,
      medical education make it more critical than ever to keep in mind what is really
      important. Deans must be exquisitely attuned to what is really important and they
      must make sure that the academic medical community never loses sight of what that
      is. To do that, deans must be deeply rooted personally in the enduring values and
      commitments that inform medicine as a profession and a vocation and in the
      fundamental values of medical education and scholarship; they must personify and
      embody these values; and they must remind us of these values and inspire us to
      embrace them and be guided by them. This is the sense in which deans must be
      "spiritual" leaders--that is, through their personal example, they must rekindle
      and engage the spirit of those working on behalf of the academic mission. While
      the need for fiscal expertise, management skills, and diplomatic and
      interpersonal skills in deans is widely acknowledged, the need for sensitivity to
      the spiritual dimensions of the work of deans has not received the attention it
      deserves.

PMID- 9653402
TI  - Leading among leaders: the dean in today's medical school.
AB  - The magnitude and pace of change in the health care environment demand that
      medical schools change. Leading in a time of great change is difficult, and it is
      ironic that just when stability in leadership is most needed, the average tenure
      of deans is dropping. Indeed, the path to leadership in academic medicine is
      strewn with inherent ironies, paradoxes, and idiosyncrasies. For example, few
      people who become leaders in academic medicine aspire to, plan for, or seek
      training for leadership, yet leadership skills are essential to meet today's
      complex institutional demands. Also, most medical school deans were once medical
      students, and were selected and trained to be assertive, independent physicians,
      not to collaborate. For faculty, the medical school environment traditionally
      values individual autonomy and rewards individual achievement, not behavior that
      supports a larger community interest. Yet today's deans must be skilled at
      collaborative behavior, since they must have a vision for their schools and find
      ways to offer direction to the faculty and others to realize that vision. The
      author offers ideas about leadership and its development, and stresses that good
      leaders must above all curtail their egos in order to do what is best for their
      institutions. What a dean does as an individual is not nearly as important as
      what a dean enables others to do. The author also provides a checklist of dean's
      characteristics and responsibilities to help deans-to-be understand the job and
      current deans to think about how to succeed and thrive. He concluded by
      reiterating that the culture of individual faculty success based on individual
      entrepreneurism is passe. To operate in the new collaborative culture, today's
      successful dean must meld persuasion with educational statesmanship, always
      informed by a vision of how the school can prosper and serve.

PMID- 9653403
TI  - Reflections on the medical deanship.
AB  - In 35 years, being dean of a medical school has changed dramatically. Thirty
      years ago, the dean's world was still the medical school and its affiliated
      hospitals, but soon this world was transformed by new emphasis on research (and
      the resources to conduct it) and the increase of specialty medicine. The medical
      school became larger and the affiliated hospital more complex. They consolidated
      into the modern academic medical center, which then became more diverse and self
      contained and eventually became an island of special expertise and achievement in
      medicine, the biomedical sciences, and clinical care. Fifteen years, ago, the
      academic medical center began to be transformed again, this time by its
      competition with or incorporation into managed care and other health care
      delivery systems. The medical school dean now operates in an environment far
      different from that of the 1960s. Deans spend 90% of their time on five major
      issues: too few resources, isolation and division of activity within the
      institution, poor management, excessive traditionalism, and too few people with
      too much to do. In addressing these issues, the dean has several powerful levers,
      including the appointment and promotion of faculty, appointments to committees
      and task forces, assignments of budget and space, and controlling the agenda and
      leading the debate in the institution. Another but less tangible issue is the
      dean's attitude. Another but less tangible issue is the dean's attitude, which
      has enormous impact on what happens at the medical school and in its programs.
      The deanship will continue but in the new context of a health care delivery
      system-with variations on the same five problems and with the same ten levers
      available to address them. The responsibility is old; only the context is new.

PMID- 9653404
TI  - Ideals in action: the U.S. Schweitzer Fellows Programs.
AB  - The inclusion of formal courses in medical ethics as part of standard
      undergraduate medical education has not led to widespread confidence in the moral
      and professional development of young physicians. As important as classes on
      informed consent and other such topics are, alternative approaches to
      professional moral development are needed. One example can be found in The U.S.
      Schweitzer Fellows Programs, which now support over 100 health professions
      students annually in six locations. Fellows participate in activities designed to
      strengthen the ideals that originally attracted them to medicine and other health
      care fields. Because Dr. Schweitzer is remembered primarily for the way he
      translated his ideals of human service into action, the core activity of each
      program is a direct-service project that addresses an important unmet health need
      of the local community or individuals in the community, with the support of
      community-based and school-based mentors. Alumni of these programs report that
      their experiences as Schweitzer fellows have helped them integrate their own
      ideals into their professional and career development. Such systematic efforts to
      recognize and support the latent idealism of young health professionals may
      strengthen the moral dimensions of professional life in ways that have broad
      social benefits.

PMID- 9653405
TI  - Considering primary care in Japan.
AB  - Involved in global competition and with a rapidly aging population, Japan is
      experiencing major reform in its medical care system and medical education
      system. Although compulsory national health insurance and accessibility to
      medical care are supported by the overwhelming majority of the Japanese people,
      rapidly increasing medical costs have been an important problem. The Japanese
      government is in the midst of changing the health insurance system from fee-for
      service to capitation, and it moved in the 1980s to reduce the number of new
      physicians as a way to control expenditures. With the lessening of government
      regulation in the 1990s, each medical school has begun to revise its curriculum
      to cope with the increasing amount of medical information available and to
      promote efficient learning. Because postgraduate clinical training programs with
      defined, comprehensive curricula are rare, and because virtually all clinical
      training is in inpatient settings, Japanese physicians' clinical competence tends
      to be insufficient for providing first-class community-based primary care. Japan
      must try to develop effective education systems in order to deliver better and
      more efficient medical care, especially primary care.

PMID- 9653406
TI  - Requiring students to have computers: questions for consideration.
AB  - For the past several years a dialogue has been taking place in the offices,
      lounges, and meeting rooms of medical schools about whether medical students
      should be required to bring or purchase computers when they enter school.
      Microcomputers offer educators a unique opportunity to provide students with
      access to computer-assisted instruction, asynchronous communication, and
      extensive knowledge bases. However, there is still no evidence attesting to the
      effectiveness of computers as teaching or learning tools in medical education.
      The author raises questions that schools need to consider before requiring
      students to own computers: What kind of computer best suits their needs? What
      might impede using computers to teach? And who is currently requiring computers?
      In addressing the last question, the author presents information about 15 North
      American schools that currently require their students to have computers,
      reporting each school's software and hardware requirements; how each expects
      students to use the computers; and who covers the cost of the computers (the
      students or the school). Finally, he argues that major institutional commitment
      is needed for computers to be successfully integrated into any medical school
      curriculum.

PMID- 9653407
TI  - What students say about learning and teaching in longitudinal ambulatory primary
      care clerkships: a multi-institutional study.
AB  - PURPOSE: Ambulatory primary care clerkships have become crucial elements in
      medical education. Although most such clerkships employ a block-rotation format,
      an alternative longitudinal approach has been developed. This study examines
      students' perceptions of learning and instruction occurring during longitudinal
      ambulatory clerkships. METHOD: Characteristics of longitudinal ambulatory primary
      care clerkships at five medical schools are described. Responses of 429 medical
      students to a standardized survey administered at these institutions are analyzed
      to ascertain perceptions of learning and teaching occurring during longitudinal
      ambulatory clerkship experiences. RESULTS: Enhancements of interpersonal
      communication and clinical skills were perceived to be the most positive learning
      attributes of the longitudinal ambulatory clerkships. No advantage was discerned
      with respect to disease-pattern recognition or generation of differential
      diagnoses. While significant inter-institutional variation was present,
      particularly with respect to instructional format, there was notable agreement
      regarding several aspects of clerkship-related learning and the adequacy of
      faculty supervision. CONCLUSION: Students perceived that learning during
      longitudinal ambulatory clerkships had greater impact on skill enhancement than
      on attainment of knowledge-related objectives. Sources of variation in student
      opinion, perceptions of learning as a function of career preference, and
      correlation of students' perceptions of learning to demonstrable changes in their
      competence require further investigation.

PMID- 9653408
TI  - Factorial validation of a widely disseminated educational framework for
      evaluating clinical teachers.
AB  - PURPOSE: To examine an instrument for evaluating clinical teaching using factor
      analysis and to refine the validated instrument to a practical length. METHOD:
      Factor analysis on a split sample of 1,581 student evaluations rating 178
      teachers. The instrument was based on the seven-category Stanford Faculty
      Development Program's (SFDP's) clinical teaching framework and contained 58
      Likert-scaled items, with at least seven items per category plus five items
      measuring "teacher's knowledge." Standard methodology for survey item reduction
      was used to remove items with low or complex factor loadings and iteratively
      remove items with low item-scale correlation. Results were replicated on the
      second sample. RESULTS: The seven original categories emerged and items
      originally categorized under "knowledge" statistically combined with "promoting
      self-directed learning." Over 73% of the variance was explained. Item reduction
      resulted in 25 items with overall internal consistency over .97 and internal
      consistency of constructs ranging from .82 to .95. CONCLUSIONS: Factor analysis
      of student ratings validated the seven-category SFDP framework. An abbreviated
      instrument to measure the seven categories is described. Results suggest that
      students may not systematically distinguish between their teachers' knowledge and
      their teachers' ability to promote self-directed learning, an important finding
      for both administrators and faculty development programs.

PMID- 9653409
TI  - A prospective randomized trial of a residents-as-teachers training program.
AB  - PURPOSE: To develop, implement, and evaluate a course for improving the teaching
      skills of surgery residents. METHOD: Responses from residents at four general
      surgery training programs to a needs assessment survey were used to develop a two
      day course for improving teaching skills. Residents at two surgical training
      programs were randomly assigned to experimental and control groups, and
      experimental residents participated in and evaluated the newly devised course.
      Six to seven months later, experimental and control residents' teaching
      performances were evaluated using a five-station objective structured teaching
      evaluation (OSTE). Differences between the residents' performances were
      calculated using Mann-Whitney U, chi-square analysis, or Fisher's exact test.
      RESULTS: Participating residents rated the course highly. They considered the
      interactive nature of the course its greatest strength. As measured by the OSTE,
      the performances of the residents differed least significantly in the feedback
      station, where the residents in the experimental groups showed significant
      improvement on only one of seven items at one institution, and only one of nine
      items at the other. The greatest differences occurred in the microskills teaching
      station, where the residents at one institution performed significantly better
      than did their control counterparts on four of five items and in overall
      performance. CONCLUSION: This study demonstrates the value of a needs assessment
      in developing a course to improve residents' teaching skills. Such courses must
      provide active learning with opportunities for practicing skills and, following
      the course, ongoing feedback to maintain changes in teaching behaviors. The
      curriculum developed in this study has been put into a transportable form that
      includes an instructor's manual providing guidelines and suggestions for
      implementation.

PMID- 9653410
TI  - A pilot study of faculty development for basic science teachers.
AB  - PURPOSE: Relatively little research has focused on faculty development methods
      that assist basic science teachers to improve their instructional skills. This
      study was designed to assess the effectiveness for basic science faculty of a
      faculty development seminar series that had been previously shown useful for
      clinical teachers. METHOD: The Stanford Faculty Development Program's seminars on
      clinical teaching were adapted for basic science instruction. Eight pathology
      faculty participated in a series of nine small-group seminars designed to provide
      teachers with knowledge of a framework for analyzing teaching and identifying
      areas for improvement, and skill-based training in specific teaching behaviors.
      Each seminar included (1) brief lectures, (2) review of videotaped reenactments
      of teaching interactions, (3) role-play exercises with videotape review, and (4)
      formulation of personal and departmental teaching goals. RESULTS: Program
      evaluation included multiple measures: participant self-assessment, student
      ratings of the participants, and blinded ratings of pre- and post-seminar
      videotapes of participants' classroom teaching. All measures indicated a positive
      effect of the intervention. CONCLUSION: Faculty development programs have
      significant potential to enhance basic science instructors' teaching
      effectiveness.

PMID- 9653411
TI  - Evaluation of primary care futures: a faculty development program for community
      health center preceptors.
AB  - PURPOSE: To assess the impact of a national series of faculty development
      workshops for community health center preceptors. METHOD: Two hundred and twenty
      three community health center preceptors from a variety of disciplines attended
      one of five workshops conducted in different regions of the country. The
      workshops emphasized active learning using role-play to provide skills in
      educational planning, teaching styles, evaluation, and feedback. The preceptors
      were evaluated before and immediately after the workshop, and again three months
      later. They were also asked to assess the quality of the workshop. RESULTS: The
      preceptors demonstrated significant increases in the use of five of seven
      teaching concepts while analyzing a role-play interaction. In addition, there
      were significant positive, immediate changes in familiarity with nine of 11
      concepts, which were retained for at least three months. The preceptors also
      reported that they continued to use six of the effective teaching behaviors they
      had learned three months after the workshop. They were extremely positive in
      their assessments of the workshops. CONCLUSION: This preliminary study suggests
      that preceptors from a variety of backgrounds can improve their teaching
      knowledge and skills by participating in a brief faculty development program that
      emphasizes active learning.

PMID- 9653412
TI  - Women in orthopedic surgery residencies in the United States.
AB  - PURPOSE: To evaluate the effect that increased numbers of women medical school
      graduates have had on the composition of orthopedic surgery residencies, and to
      evaluate trends over time in the likelihood of women medical students to select
      orthopedic residencies. METHOD: The author analyzed JAMA's "Reports on Graduate
      and Undergraduate Medical Education" for the years 1977 to 1996, calculating the
      numbers of women and men in orthopedic surgery and other surgery residencies, and
      medical school composition. RESULTS: Although there have been modest gains in the
      number of women in orthopedic surgery training programs in the United States,
      women continue to choose orthopedics only one-seventh as often as do men.
      CONCLUSION: Orthopedics remains an unattractive career choice for women medical
      students compared with their men counterparts. Biases and stereotypes about women
      and about orthopedic surgery may account for this difference.

PMID- 9653413
TI  - Knowledge of and attitude toward patient confidentiality within three family
      medicine teaching units.
AB  - PURPOSE: To describe the knowledge and attitudes about confidentiality issues
      within family medicine teaching units (FMUs) at McGill University. METHOD: The
      authors surveyed McGill University FMU staff (physicians, nurses, and support
      staff) on their knowledge of and attitudes toward confidentiality issues.
      RESULTS: The response rate was 84%. Only one of nine questions on confidentiality
      laws was correctly answered by more than 80% of the respondents. Only 55% of the
      support staff knew that police are not permitted free access to charts, although
      the majority of those who answered incorrectly held attitudes that were
      consistent with the law. Only approximately 25% knew that physicians and nurses
      are not permitted free access to any medical record within the center. There were
      minimal differences between the professions or between the FMUs. CONCLUSION:
      These findings suggest that FMU staff do not fully understand their obligations
      towards patient confidentiality.

PMID- 9653414
TI  - New bottles for vintage wines: the changing management of the medical school
      faculty.
AB  - Medical schools are being challenged to develop innovative mechanisms of faculty
      governance and management that enlist faculty in meeting the demands of a
      competitive marketplace. The authors describe some of these mechanisms in this
      article, which is the result of case studies made in 1997 of ten schools.
      Measures to increase the accountability of faculty to the strategic directions of
      the school include having appointment letters that specify explicitly the roles
      and responsibilities of the faculty member, conducting annual performance reviews
      based upon more objective criteria, tying salary to performance, lengthening the
      pre-tenure probation period, instituting post-tenure review, and redefining the
      salary guarantees of tenured faculty. Equally important is balancing these
      policies with initiatives to strengthen the accountability of schools to their
      faculty. Improved methods of communication between administrators and faculty and
      more efficient processes to enable faculty to participate in decision making are
      appearing. Formal approaches to mentoring and faculty development are being
      implemented. Recognition and reward programs are being strengthened. Alternatives
      to tenure are being developed in recognition of the need for increasingly diverse
      roles of faculty and to ensure job security. The reengineering of the processes
      that will lead to shared vision and accountability will require massive cultural
      change. The realization of these goals is likely to depend on the skill of
      medical school managers and the ability and willingness of faculty members to
      work collaboratively and creatively in designing new methods to accomplish old
      missions. Next month's AAMC Paper will explore changes in the structure and
      management of medical schools and their owned or closely affiliated facilities to
      improve the efficiency of achieving their core missions.

PMID- 9653415
TI  - Oppositional defiant disorder symptomatology after traumatic brain injury: a
      prospective study.
AB  - Our goal was to prospectively study the course of oppositional defiant disorder
      (ODD) symptomatology in children and adolescents in the first 2 years after
      traumatic brain injury (TBI). Fifty children aged 6 to 14, hospitalized after
      TBI, were assessed soon after TBI regarding injury severity; preinjury
      psychiatric, socioeconomic, family functioning, and family psychiatric history
      status; and neuroimaging was analyzed. ODD symptomatology in the first year after
      TBI was related to preinjury family function, social class, and preinjury ODD
      symptomatology. Increased severity of TBI predicted ODD symptomatology 2 years
      after injury. Change (from before TBI) in ODD symptomatology at 6, 12, and 24
      months after TBI was influenced by socioeconomic status. Only at 2 years after
      injury was severity of injury a predictor of change in ODD symptomatology. The
      influence of psychosocial factors appears greater than severity of injury in
      accounting for ODD symptomatology and change in such symptomatology in the first
      but not the second year after TBI in children and adolescents. This appears
      related to persistence of new ODD symptomatology after more serious TBI.

PMID- 9653416
TI  - Acute stress disorder after mild traumatic brain injury.
AB  - The debate continues over whether a posttraumatic response occurs in those who
      have sustained a traumatic brain injury (TBI). The aim of this study was to
      investigate the incidence of acute stress disorder (ASD) in the mild TBI
      population. Patients who sustained a mild TBI after a motor vehicle accident (N =
      79) were assessed for the presence of ASD. ASD was diagnosed in 13.9% of
      patients, and 5.1% were diagnosed with subsyndromal ASD. Dissociative,
      reexperiencing, and avoidance symptoms were found to have moderate to high
      predictive power. This study highlights the significant number of patients who
      experience an acute trauma response after TBI and raises the possibility that
      those with ASD denote those for whom an early intervention may prevent longer
      term psychopathology. Diagnostic difficulties in defining ASD after TBI are
      discussed.

PMID- 9653417
TI  - The relationships between premilitary school record data and risk for
      posttraumatic stress disorder among Vietnam war veterans.
AB  - The purpose of this study was to determine whether Vietnam veterans' risk for
      posttraumatic stress disorder (PTSD) was correlated with their premilitary school
      performance. The authors compared both primary and secondary school record data
      on hospitalized chemically dependent PTSD patients with those of both non-PTSD,
      chemically dependent and community controls. All participants were male Vietnam
      war combat veterans. The comparisons were made with MANCOVA analyses with the
      effects of combat and age differences between groups controlled. For the most
      part, primary-school grade point average, absenteeism, and tardiness data on
      three groups did not differ significantly. However, the mean secondary school
      grade points of the future PTSD patients were generally substantially lower than
      those of controls. Additionally, more secondary school absenteeism and tardiness
      were reported among future PTSD patients than in the controls. The groups did not
      differ significantly on number of extracurricular activities. Academic weakness,
      absenteeism, and tardiness in secondary school appear to be moderately strong
      predictors of vulnerability to PTSD after traumatization. It also supports the
      claim that chronic PTSD is, in part, the result of weaknesses present before
      exposure to trauma.

PMID- 9653418
TI  - Twin study of dissociative experience.
AB  - The relative influence of genetic and environmental influences on measures of
      pathological and nonpathological dissociative experience was estimated using a
      classic twin-study design. Subjects were 177 monozygotic and 152 dizygotic
      volunteer general population twin pairs who completed two measures of
      dissociative capacity identified from the items comprising the Dissociative
      Experiences Scale (DES). Additive genetic influences accounted for 48% and 55% of
      the variance in scales measuring pathological and nonpathological dissociative
      experience, respectively. Heritability estimates did not differ by gender. The
      genetic correlation between these measures was estimated at .91, suggesting
      common genetic factors underlying pathological and nonpathological dissociative
      capacity. Genetic and environmental correlations between the DES scales and
      measures of personality disorder traits (Dimensional Assessment of Personality
      Pathology-Basic Questionnaire; DAPP-BQ) were also estimated. Significant genetic
      correlations (median = .38) were found between the DES scales and DAPP-BQ
      cognitive dysregulation, affective lability, and suspiciousness, suggesting that
      the genetic factors underlying particular aspects of personality disorder also
      influence dissociative capacity.

PMID- 9653419
TI  - Axis II pathology in outpatients with dissociative identity disorder.
AB  - Forty-two outpatients with dissociative identity disorder (DID) and 16
      outpatients with dissociative disorder not otherwise specified (DDNOS) were
      administered the Millon Clinical Multiaxial Inventory-II (MCMI-II), the Minnesota
      Multiphasic Personality Inventory-2 (MMPI-2), and the Dissociative Experiences
      Scale (DES). DID patients manifested severe personality pathology (BR > 84) on a
      mean of 4.0 MCMI-II scales: avoidant (76%), self-defeating (68%), borderline
      (53%), and passive-aggressive (45%). DDNOS cases had severe personality pathology
      on fewer MCMI-II scales (mean = 1.69): avoidant (50%) and self-defeating (31%).
      The DID and DDNOS groups differed in their scores on the DES (means = 54.9 vs.
      25.9), the PK-PTSD scale of the MMPI-2 (means = 33.6 vs. 21.7), and in the
      incidence of severe borderline pathology (53% vs. 6%). These data on personality
      pathology in DID patients are virtually identical to those of seven previous
      studies of personality pathology in chronic PTSD patients (i.e., avoidant, self
      defeating, borderline, and passive-aggressive). Such robust convergence of
      findings supports the construct validity of DID as a form of posttraumatic
      disorder and suggests that there is a quite predictable personologic core to the
      clinical picture of severely traumatized individuals.

PMID- 9653420
TI  - Remission and relapse in schizophrenia: the Madras Longitudinal Study.
AB  - This paper uses monthly symptom data on 90 first-onset schizophrenics in Madras,
      India, to characterize, in a continuous manner, the course of remission and
      relapse. Remission from the first episode occurs in about 6 months and in about 3
      months for later episodes. Syndromes from the Present State Exam, assessed at the
      first episode, predict differentially to early and later parts of the course.
      Hypomania and simple depression predict early remission from the first episode;
      flat affect and grandiose delusions predict longer episodes and shorter
      remissions later in the course.

PMID- 9653421
TI  - Causal mechanisms of subjective cognitive dysfunction in schizophrenic and
      depressed patients.
AB  - We examined causal mechanisms of subjective cognitive (dis)abilities in
      schizophrenic and depressed patients, and in patient and normal control groups.
      This exploratory study included objective cognitive performance (Continuous
      Performance Task) as well as mood and mental effort ratings. Self-report of
      cognitive dysfunction in patients was not correlated with objective cognitive
      deficits. Correlational patterns differed between groups. Our findings in
      schizophrenic and depressed patients point to different causal mechanisms of
      their subjective cognitive malaise, despite similar subjective ratings. Depressed
      patients associate high mental effort during task performance with a reduced
      cognitive efficacy, whereas schizophrenic patients associate high effort with
      cognitive symptoms like distractibility and overload.

PMID- 9653422
TI  - The effects of interviewer gender in mental health interviews.
AB  - Despite indications that gender can affect the disclosure of personal
      information, few studies examine the effects of interviewer gender in eliciting
      information pertaining to psychological functioning and mental health. Analysis
      of data collected at the Los Angeles site of the Epidemiological Catchment Area
      Study reveals that interviewer gender is significantly related to respondents'
      reports of psychiatric symptoms. Male and female respondents interviewed by women
      report more symptoms of depression, substance abuse, and conduct disorders than
      respondents interviewed by men. It is suggested that female interviewers may
      create conditions more conducive to disclosure and be perceived as more
      sympathetic than male interviewers. Although limitations of both data and
      analysis preclude a definitive conclusion, the findings suggest that interviewer
      gender may influence disclosure in mental health and related types of interviews.

PMID- 9653423
TI  - Expressed emotion and locus of control.
AB  - Expressed emotion is a robust and reliable predictor of psychiatric relapse
      across a range of psychopathological conditions and diagnoses. Theoretical
      speculation about the expressed emotion construct has suggested that high levels
      of criticism in relatives might be linked to attributions and beliefs about the
      patient's ability to control his or her symptoms or problem behaviors. Although
      there is some empirical support for this notion, no study to date has examined
      relatives' beliefs about their own abilities to control problem situations. This
      study compared high- and low-critical relatives of patients with schizophrenia on
      a measure of locus of control. Consistent with prediction, the locus of control
      scores of high-critical relatives were indicative of a more internal locus of
      control, whereas those of the low-critical relatives were indicative of a more
      external locus of control.

PMID- 9653424
TI  - Ginkgo biloba for dementia.

PMID- 9653425
TI  - A new rabies vaccine.

PMID- 9653426
TI  - Rituximab for non-Hodgkins lymphoma.

PMID- 9653427
TI  - Cryptococcal pneumonia complicating pregnancy.
AB  - In the present report we describe 4 previously healthy women who developed
      cryptococcal pneumonia during pregnancy, and 1 pregnant woman with cryptococcal
      meningitis. These cases illustrate a previously uncharacterized spectrum of
      cryptococcal disease. We also discuss 24 patients previously reported who had
      cryptococcal meningitis during pregnancy. Finally, we review the available data
      for each therapeutic option and present an algorithm for management based on
      appraisals of disease severity and risk to the unborn fetus. This report
      emphasizes the need for heightened awareness of cryptococcosis in the
      differential diagnosis of pneumonia, chest pain, and hypoxemia in the pregnant
      patient, but at present, there are insufficient epidemiologic data to determine
      whether incidences of pulmonary or disseminated cryptococcosis actually increase
      during pregnancy. The risk of congenital cryptococcosis to the unborn fetus is
      low, and the most likely mechanism whereby neonates acquire invasive fungal
      pulmonary infection is through aspiration. While it is unclear whether there is
      any real increased risk of spontaneous abortion or premature labor, the data
      indicate that overall fetal outcome depends on effective treatment of maternal
      infection. For patients with dense air-space consolidation, progressive pulmonary
      disease, or dissemination, antifungal therapy is necessary. Optimal treatment is
      determined by the acuity and severity of the clinical presentation. Amphotericin
      B (approximately 1 g) with or without flucytosine represents the choice for
      initial treatment of the more acutely ill patient with disseminated or
      progressive pulmonary cryptococcosis who requires hospitalization (whether during
      or after pregnancy). Oral fluconazole appears to be safe and effective
      alternative therapy after delivery for the less severely ill patient who can be
      managed on an outpatient basis. While the use of fluconazole during pregnancy
      generally appears safe in terms of fetal outcome (49, 58), the class C status and
      single report of fetal malformation (62) preclude confident recommendation for
      its use during pregnancy. The risks and benefits of this effective and generally
      less toxic drug should be discussed with the parents and weighed against the use
      of amphotericin B. For pregnant women with limited pulmonary cryptococcosis
      (segmental or nodular infiltrates) and no evidence of dissemination, we recommend
      close follow-up without antifungal therapy similar to the recommendation for
      normal hosts with minimal disease. However, it is important to note that there is
      no extensive experience upon which to base this recommendation for pregnant
      individuals (45, 55, 103, 108). It is prudent to use frequent physical
      examinations (for example, every 1-2 months), combined with chest roentgenograms
      and serum cryptococcal antigens to monitor progression and/or development of
      disease in both the mother and child for approximately 6 months postpartum. In
      conclusion, cryptococcosis during pregnancy presents a special challenge to the
      clinician. A balanced therapeutic approach holds great promise for successful
      maternal and fetal outcomes.

PMID- 9653428
TI  - Respiratory involvement in relapsing polychondritis. Clinical, functional,
      endoscopic, and radiographic evaluations.
AB  - Although respiratory involvement occurs in 50% of patients with relapsing
      polychondritis (RP) and augurs a poor prognosis, few previous studies have
      provided complete descriptions of respiratory tract involvement. For this reason,
      we investigated the respective role of clinical, functional, endoscopic, and
      radiographic (computed tomography [CT]) examinations in 9 consecutive patients
      with RP and lower respiratory tract localization. All exhibited cough, dyspnea,
      and wheezing. Eight had a nonreversible obstructive pattern with a marked
      decrease of the maximal flow ratio at 75% and 25% of vital capacity. Rotman
      functional criteria were evaluated to differentiate upper from lower respiratory
      tract involvement; they were consistent with the results of other examinations in
      4/9 cases. Endoscopic examination showed moderate to severe inflammation in 8/9
      patients; tracheal stenosis was present in 6/9 patients, bronchial stenosis in
      4/9 patients, and tracheal collapse in 7 cases. CT showed tracheal stenosis in
      8/9 patients (diffuse, 7; localized, 1) and bronchial stenosis in 6/9 patients.
      Tracheobronchial wall thickening and/or calcifications were observed in 7 cases.
      Clinical symptoms are of poor specificity for defining respiratory involvement
      precisely, although degree of dyspnea is correlated to the decrease in forced
      expiratory volume in 1 second (FEV1). Functional criteria were helpful in
      evaluating the obstructive ventilatory defect but did not differentiate, in most
      cases, the respective part of lower and upper respiratory involvement when using
      Rotman criteria. Compared to CT findings, endoscopic examination failed to
      identify tracheal and bronchial stenosis and tracheal wall alterations at an
      early stage of the disease. In our series CT appears to be a reliable method to
      identify tracheal and bronchial involvement and can be repeated safely during the
      course of the disease.

PMID- 9653429
TI  - Septic arthritis of the glenohumeral joint. A report of 11 cases and review of
      the literature.
AB  - Eleven cases (6 adults and 5 pediatrics) of shoulder septic arthritis are
      described, and the English literature from 1960 to 1997 reviewed, for a total of
      168 cases. Shoulder septic arthritis is an uncommon and difficult diagnosis
      requiring a high index of suspicion and early evaluation of the affected shoulder
      by the clinician. The disease usually involves very young infants or elderly
      patients (65-75 years old). Associated medical conditions were identified in 60%
      of the patients and include systemic disorders such as liver diseases,
      alcoholism, and malignancies in 46%; preceding chronic arthritic disorders in
      24%; and associated infectious focus in 13% of the patients. Associated
      infections were more prevalent in the pediatric population. Intravenous drug
      abuse appears not to constitute a major risk factor; it was identified in less
      than 5% of patients. All patients presented with acute shoulder ache or with
      exacerbation of existing chronic pain in joints previously damaged. Elevated body
      temperature (over 38 degrees C) appeared in 67% of the adult patients and in over
      90% of the pediatric patients. Shoulder arthritis was frequently accompanied by
      an accelerated erythrocyte sedimentation rate that may rise above 100 mm/hr.
      Increased white blood cell count was found in approximately 40% of patients. The
      initial X-rays were frequently normal, while ultrasonography supported the
      diagnosis in some cases by demonstrating accumulation of fluid inside the joint
      space. Aspiration of synovial fluid from the affected glenohumeral joint was
      necessary to evaluate the offending pathogen. False-negative Gram stain appeared
      in approximately 90% of the patients, whereas synovial fluid cultures
      demonstrated the pathogen in 88% of patients. Blood cultures were positive in 50%
      of adult patients and 90% of pediatric patients. The most common isolated
      pathogen was Staphylococcus aureus, which accounted for 41% of infections. Gram
      negative bacilli, which accounted for about 20% of infections, are more prevalent
      in the pediatric population, especially the neonates. Pyogenic shoulder arthritis
      should first be treated with intravenous antibiotics, effective at least against
      staphylococcal infections, until the organisms and sensitivities are identified.
      Duration of antibiotic therapy should be 3-6 weeks. Unfortunately, our experience
      in addition to the literature summary does not allow statistical analysis and
      firm conclusions concerning the best therapeutic approach. However, it appears
      that in the adult population an operative draining procedure is preferred,
      whereas in the pediatric population, a closed needle aspiration, if needed at
      all, is the optimal treatment. With prompt antibiotic therapy and drainage of the
      shoulder, the patient can be expected to improve clinically, with no serious long
      term debilitating effects from the disease.

PMID- 9653430
TI  - Invasive aspergillosis. Clinical features of 35 proven cases at a single
      institution.
AB  - Thirty-five patients with clinical features and histologically or
      microbiologically proven infection met predetermined stringent criteria for
      invasive aspergillosis over a 5-year period at our institution. Underlying
      conditions included hematologic malignancy, solid tumor, bone marrow and solid
      organ transplantation, and immunosuppressive therapy. The majority of patients
      (94%) presented with respiratory symptoms and abnormal pulmonary chest
      radiography; only 40% had neutropenia at time of infection. Invasive
      aspergillosis was suspected in only 21 cases (60%). Concomitant infections were
      present in 83% of patients. Half of patients had pathogenic or potentially
      pathogenic microorganisms other than Aspergillus spp. isolated from pulmonary
      specimens at time of aspergillosis. Aspergillus spp. were recovered from sputum
      in 75% of patients and from bronchoalveolar lavage in only 52%. Invasive
      aspergillosis is an unexpectedly unrecognized disease with poor outcome; overall
      mortality was 94% in our series. The lack of sensitivity of diagnostic
      procedures, together with the high frequency of concomitant infections, delays
      the time of diagnosis. Early diagnostic tests are needed, and presumptive
      antifungal therapy among high-risk patients is mandatory.

PMID- 9653432
TI  - Breast cancer susceptibility genes. BRCA1 and BRCA2.
AB  - Mutations in the BRCA1 and BRCA2 genes lead to an increased susceptibility to
      breast, ovarian, and other cancers. It is estimated that 3%-8% of all women with
      breast cancer will be found to carry a mutation in 1 of these genes. Families
      with multiple affected first-degree relatives and patients with early-onset
      disease have been found to harbor mutations at a higher frequency. The BRCA1 and
      BRCA2 genes code for large proteins that bear no resemblance to other known
      genes. In the cell, they appear to act as tumor suppressor genes and play a role
      in the maintenance of genome integrity, although the precise function of these
      genes has yet to be discovered. A large number of distinct mutations have been
      found in cancer families around the world. The majority of the defined pathologic
      mutations result in premature truncation of the protein (frameshift and nonsense
      mutations). These mutations may substantially increase the risk for breast and
      ovarian cancer, but a precise risk estimate for each different mutation cannot be
      determined. Depending on the familial context, the risk of breast cancer
      associated with carrying a mutation has been estimated to range from 50% to 85%.
      The role of these genes in sporadic cancer remains unknown. Patients and
      physicians considering BRCA1 and BRCA2 genetic testing are faced with a difficult
      decision. The diversity of mutations and lack of general population data prevent
      accurate risk prediction. This is further complicated by the paucity of data on
      effective prevention strategies for those identified at higher risk. Thus, the
      nature of clinical testing for BRCA1 and BRCA2 continues to present challenges
      that reinforce the necessity of personal choice within the context of thorough
      genetic counseling.

PMID- 9653431
TI  - Catastrophic antiphospholipid syndrome. Clinical and laboratory features of 50
      patients.
AB  - We analyzed the clinical and laboratory characteristics of 50 patients with
      catastrophic antiphospholipid syndrome (APS) (5 from our clinics and 45 from a
      MEDLINE computer-assisted review of the literature from 1992 through 1996).
      Thirty-three (66%) patients were female and 17 (34%) were male. Twenty-eight
      (56%) patients had primary APS, 15 (30%) had defined systemic lupus erythematosus
      (SLE), 6 (12%) had "lupus-like" syndrome, and 1 (2%) had rheumatoid arthritis.
      Mean age of patients in this series was 38 +/- 14 years (range, 11-74 yr). Three
      (6%) patients developed the clinical picture of catastrophic APS under the age of
      15 years, and 11 (22%) were 50 years old or more. In 11 (22%) patients,
      precipitating factors contributed to the development of catastrophic APS
      (infections in 3, drugs in 3, minor surgical procedures in 3, anticoagulation
      withdrawal in 2, and hysterectomy in 1). The presentation of the acute multi
      organ failure was usually complex, involving multiple organs simultaneously or in
      a very short period of time. The majority of patients manifested microangiopathy-
      that is, occlusive vascular disease affecting predominantly small vessels of
      organs, particularly kidney, lungs, brain, heart, and liver--with a minority of
      patients experiencing only large vessel occlusions. Thrombocytopenia was reported
      in 34 (68%) patients, hemolytic anemia in 13 (26%), disseminated intravascular
      coagulation in 14 (28%), and schistocytes in 7 (14%). The following antibodies
      were detected: lupus anticoagulant (94%), anticardiolipin antibodies (94%), anti
      dsDNA (87% of patients with SLE), antinuclear antibodies (58%), anti-Ro/SS-A
      (8%), anti-RNP (8%), and anti-La/SS-B (2%). Anticoagulation was used in 70% of
      the patients, steroids in 70%, plasmapheresis in 40%, cyclophosphamide in 34%,
      intravenous gammaglobulins in 16%, and splenectomy in 4%. Most patients, however,
      received a combination of nonsurgical therapies. Death occurred in 25 of the 50
      (50%) patients. In most, cardiac problems seemed to be the major cause of death.
      In several of these, respiratory failure was also present, usually due to acute
      respiratory distress syndrome and diffuse alveolar hemorrhage. Among the 20
      patients who received the combination of anticoagulation, steroids, and
      plasmapheresis or intravenous gammaglobulins, recovery occurred in 14 (70%)
      patients. The use of ancrod and defibrotide appeared to be effective in the 2
      respective patients in whom they were used.

PMID- 9653433
TI  - New ways to ventilate newborns in acute respiratory failure.
AB  - Out treatment options for acute neonatal failure have expanded greatly in the
      last 20 to 30 years. This article reviews patient-triggered ventilation, high
      frequency ventilation, negative extrathoracic pressure ventilation, nitric oxide
      therapy, liquid ventilation, extracorporeal membrane oxygenation, and advances in
      pulmonary function monitoring. The authors present background theories, describe
      equipment, review clinical strategies, and the results of recent trials.

PMID- 9653434
TI  - Meconium-stained amniotic fluid and the meconium aspiration syndrome. An update.
AB  - Over the past 5 years, increasing understanding about the pathophysiology of
      meconium-stained amniotic fluid (MSAF) and the meconium aspiration syndrome (MAS)
      has occurred. Many new therapies are being used in an attempt to prevent MAS and
      to treat the disorder. The authors review the current status of knowledge
      concerning the MSAF and MAS and management of these entities.

PMID- 9653435
TI  - The use of inhaled nitric oxide in a wide variety of clinical problems.
AB  - Inhaled nitric oxide (NO) clearly decreased pulmonary vascular resistance in
      pediatric patients with pulmonary hypertension, regardless of the underlying
      origin of the pulmonary hypertension. In persistent pulmonary hypertension of the
      neonate (PPHN) and CHD, the use of inhaled NO appears to improve the outcome of
      these patients. In acute respiratory distress syndrome (ARDS) and surfactant
      deficiency the role of inhaled NO therapy remains unclear. The use of inhaled NO
      is safe in a carefully monitored setting with a delivery system designed to
      minimize the generation of NO2.

PMID- 9653436
TI  - Surfactant replacement therapy. An update on applications.
AB  - Surfactant replacement therapy has been shown to be an effective and often life
      saving treatment for newborn infants with respiratory distress syndrome (RDS).
      This article provides the clinician with an update regarding the various other
      applications of surfactant replacement therapy, as well as issues related to
      surfactant administration for the preparations approved for use in pediatric
      patients.

PMID- 9653437
TI  - Bronchopulmonary dysplasia. Impact of surfactant replacement therapy.
AB  - Bronchopulmonary dysplasia is a major contributor to the morbidity and mortality
      of infants born prematurely. Surfactant replacement therapy has had a significant
      impact on the death rate from respiratory distress syndrome, yet the impact on
      bronchopulmonary dysplasia is minimal. Despite these findings, the overall
      incidence and severity of bronchopulmonary dysplasia are likely to decline over
      time as neonatal care continues to advance.

PMID- 9653438
TI  - Neonatal cardiopulmonary resuscitation: the good news and the bad.
AB  - Many health care professionals all over the world have been taught neonatal
      cardiopulmonary resuscitation (CPR) using the neonatal CPR course based upon the
      work of Bloom and Cropley. The purpose of this article is to provide a
      retrospective review of the development of some of the neonatal CPR techniques,
      to discuss current techniques and to complement the dedication of this issue to
      Dr. Ronald Brown and Catherine Copley, MN, RN.

PMID- 9653439
TI  - Advances in fetal surgery.
AB  - The use of maternal/fetal ultrasound screening has become commonplace in today's
      society. The principle behind fetal surgery evolves around the potential of
      correction or interruption of various abnormal processes that may bring about
      fetal demise or can become life-threatening to the newborn. This article reviews
      the progressive technical improvements and advances in fetal surgery.

PMID- 9653440
TI  - Advances in neonatal surgery.
AB  - Neonatal surgery has reached a high degree of sophistication. We are now entering
      a new era of widespread screening of the unborn by means of ultrasound, with
      planned intrauterine, intrapartum, and immediate postpartum interventions. Many
      pediatric surgical centers are now focusing their investigative efforts on
      elucidating the cellular, molecular, and biochemical response to disease and
      therapeutic agents. The author presents the topic of neonatal surgery to some of
      the newer applications, techniques, and approaches.

PMID- 9653441
TI  - Future financial neonatal shock.
AB  - In a changing economic climate, the neonatologist must be aware of all of the
      forces that can affect the practice of neonatology. In addition to clinical
      issues, billing and reimbursement must take into account physician work and
      common procedural terminology (CPT) codes, which accurately describe the medical
      services and procedures delivered. An understanding of this coding and resource
      based work unit system is necessary to prevent financial loss. The influence of
      managed care, capitation, fixed per-case reimbursement, practice guidelines and
      care maps have already seriously affected clinical practice patterns. The
      neonatologist must be proactive in negotiating contracts using historic
      information and outcome data to define and defend the quality of care provided.

PMID- 9653442
TI  - Permanent presence of managed care and outcome of critically ill infants.
AB  - In the era of managed care, the potential for high-risk patients of all ages to
      receive less than optimal care exists because the mechanism for reimbursement is
      designed to promote savings. The specific ways managed care payment mechanisms
      actually differ from indemnity insurance or fee-for-service are conceptually
      quite simple. This article reviews mechanisms such as utilization review, setting
      length-of-stay bench marks, preapproval for referrals to specialists, specific
      treatments, procedures, and hospital days.

PMID- 9653443
TI  - Principles of disease management in neonatology.
AB  - This article emphasizes the emerging facets of disease-management practice that
      impact directly on establishing a measured care system that can produce the
      information needed to establish a continuous quality improvement program. The
      areas discussed are risk assessment, clinical management guidelines and
      carepaths, and the measurement of system output known as clinical outcomes. The
      remainder of the article details the aspects of risk assessment, guideline
      function, and outcome assessment, critical in a disease-managed measured care
      system.

PMID- 9653444
TI  - Developmental outcome in very low birthweight infants. Current status and future
      trends.
AB  - Surfactant therapy has significantly reduced mortality, but not morbidity, in the
      very low birthweight (VLBW) infant. Questions persist as to the edge of
      viability, the allocation of health care resources for the VLBW infant, and
      whether or not we are improving survival at the cost of contributing more
      handicapped individuals to society. Since surfactant alone has not reduced
      morbidity, other medical and behavioral treatments are being studied that may
      help to optimize neurodevelopmental outcome in the VLBW infant.

PMID- 9653445
TI  - The death of a baby in the infant special care unit.
AB  - We are learning about the meaning of the death of an infant, and its impact on
      the family. We are becoming aware that by being there, health care staff become
      important in how the life-long process of grieving will get started. Educational
      and supportive practices for staff and programs for bereaved family members that
      set the stage for healthy grieving are difficult but valuable in the work of
      neonatal intensive care.

PMID- 9653446
TI  - Caring for the graduate from the neonatal intensive care unit. At home, in the
      office, and in the community.
AB  - This article focuses on recent progress in the understanding of optimal care for
      the neonatal intensive care unit (NICU) graduate in three domains that have
      relevance to primary care pediatricians: the concept of developmentally
      supportive care for the immature central nervous system of fragile premature
      infants; an understanding of the function and systems of community-based early
      intervention available for medically complex, developmentally challenged and at
      risk infants; and the management of technology-dependent children at home.

PMID- 9653447
TI  - Mammalian base excision repair and DNA polymerase beta.

PMID- 9653448
TI  - Database of mouse strains carrying targeted mutations in genes affecting cellular
      responses to DNA damage. Version 2.

PMID- 9653449
TI  - Repair of cyclobutane pyrimidine dimers in the O6-methylguanine-DNA
      methyltransferase (MGMT) gene of MGMT proficient and deficient human cell lines
      and comparison with the repair of other genes and a repressed X-chromosomal
      locus.
AB  - We studied the repair of cyclobutane pyrimidine dimers (CPDs) in the 5' terminal
      part of the transcriptionally inactive O6-methylguanine-DNA methyltransferase
      (MGMT) gene of MGMT-deficient human cell lines (A172, A-253 and WI-38 VA13) and
      in a proficient cell line (HaCaT), in which the MGMT gene was transcribed. Repair
      rates in the MGMT gene were compared with those in the active uracil-DNA
      glycosylase (UNG) and c-myc genes, and those in the repressed X-linked 754 locus
      and the RNA polymerase I-transcribed ribosomal gene cluster. In the active MGMT
      gene, there was a distinct strand specificity with more repair in the template
      (transcribed) strand (TS) than in the non-template strand (NTS). In contrast, no
      apparent strand bias in the repair of CPDs was observed in the inactive MGMT gene
      in the MGMT deficient cell lines, although the rates of repair varied between
      different cell lines. Repair in the inactive MGMT gene was consistently lower
      than repair in the NTSs of the expressed genes, and approached the generally poor
      repair of the repressed 754 locus. Whereas repair in the UNG gene was strand
      specific in HaCaT, A-172 and WI-38 VA13 cells, no clear strand bias in repair of
      this gene was evident in A253 cells and repair was relatively inefficient.
      Although the repair kinetics was essentially similar in the two strands of the c
      myc gene in all cell lines examined, the rate and extent of repair were in
      general significant, probably due to an observed transcription of both strands in
      the c-myc region. In conclusion, our results indicate that the relative rates of
      repair in inactive MGMT genes are comparable to those of repressed loci and are
      lower than repair rates in the NTSs of active genes, but the absolute rate of
      repair varies between different transformed cells.

PMID- 9653450
TI  - Mechanisms determining sensitivity to cisplatin in three mutant Chinese hamster
      ovary cell lines.
AB  - To gain insight into factors determining the response of tumours to cisplatin, we
      studied pathways involved in resistance to cisplatin: drug uptake, cytoplasmic
      detoxification and DNA repair, in three cisplatin-sensitive Chinese hamster ovary
      (CHO)2 mutant cell lines. The mutant lines, CHO-MMC6, CHO-MMC1, CHO-MMS2,
      displayed inherent sensitivity to cisplatin (2.2, 4.1 and 10.6-fold,
      respectively) compared to the CHO-K1 line from which they were derived. CHO-MMS2
      was the only mutant to show sensitivity to UV and this was slight (< 2-fold).
      None of the mutants displayed increased sensitivity to X-irradiation. The CHO
      MMS2 cell line appeared to have multiple mechanisms involved in its sensitivity
      to cisplatin, including increased drug accumulation, decreased levels of
      glutathione and a decreased capacity for DNA repair. The CHO-MMC1 mutant
      demonstrated reduced ability for DNA repair in a host cell reactivation assay,
      but no difference in drug accumulation or glutathione levels compared to the
      parent. The CHO-MMC6 cell line was not defective in any of the mechanisms
      studied. These three mutant cell lines demonstrate that similar mechanisms may
      account for inherent sensitivity or resistance to cisplatin, and suggest that
      multiple mechanisms may determine the sensitivity of human tumours to cisplatin.

PMID- 9653451
TI  - Hydrogen peroxide induces protection against lethal effects of cumene
      hydroperoxide in Escherichia coli cells: an Ahp dependent and OxyR independent
      system?
AB  - Pretreatment with 2.5 mM H2O2 protects bacterial cells against cumene
      hydroperoxide killing. This response is independent of the OxyR system, but
      possibly involves the participation of Ahp protein, since ahp mutants are not
      protected. Treatment of bacterial cells with high H2O2 concentrations caused an
      alteration on the electrophoretic profile of the smaller subunit (22-kDa) of Ahp.
      This alteration does not require novel gene products and is not dependent on the
      OxyR protein. In this way, we propose that the modification of the 22-kDa subunit
      of Ahp by high H2O2 concentration may be responsible for the protection against
      the lethal effects of cumene hydroperoxide.

PMID- 9653452
TI  - Proficient deoxyribonucleic acid repair of methylation damage in hamster ERCC
      gene mutants.
AB  - Three major pathways, nucleotide excision repair (NER), base excision repair
      (BER) and O6-methylguanine-DNA methyltransferase (MGMT), are responsible for the
      removal of most adducts to DNA and thus for the survival of cells influenced by
      deoxyribonucleic acid (DNA) adduct-forming chemicals. We have evaluated host cell
      reactivation and cell survival of wild type Chinese hamster ovary cells and of
      mutants in the NER-genes ERCC1, ERCC2, and ERCC4 after treatment with the
      methylating compounds dimethylsulfate and methylnitrosourea. No effect of the
      three genes could be demonstrated, i.e., survival and host cell reactivation
      after methylation damage in the mutants and the wild type cells were similar.
      Gene-specific repair experiments confirmed the proficient removal of methyl
      lesions. We conclude that the three nucleotide excision repair genes are
      immaterial to the repair of methylation damage. This suggests that NER does not
      play a role in the removal of methylation in mammalian cells and that BER and
      MGMT are responsible for the survival of such cells, when they are challenged
      with methylation of DNA.

PMID- 9653453
TI  - ERCC1 mutations in UV-sensitive Chinese hamster ovary (CHO) cell lines.
AB  - In mammalian nucleotide excision repair (NER), the ERCC1 protein is known to act
      as a complex with ERCC4 (XPF) protein, which is necessary for stability of ERCC1,
      and this complex introduces an incision on the 5' side of a damaged site in DNA.
      ERCC1 also binds to XPA protein to make a large protein complex at the site of
      DNA damage. Since no human disease associated with ERCC1 has been identified,
      Chinese hamster ovary (CHO) cell lines defective in ERCC1 are a unique source for
      characterization of ERCC1 deficiency in mammalian cells. We have isolated the
      full length ERCC1 cDNA from a wild-type CHO cell line and analyzed mutations in
      two CHO cell lines which fall into complementation group 1 of UV-sensitive rodent
      cell lines. One cell line, 43-3B, has a missense mutation at the 98th residue
      (V98E). The in vitro translated mutant protein of 43-3B is unable to bind to XPA
      protein. Although the mutant protein is able to bind to XPF protein in vitro, the
      mutant protein is highly unstable in vivo. These defects presumably cause the NER
      deficiency of this cell line. Another mutant, UV-4, has an insertion mutation in
      the middle of the coding sequence, resulting in a truncated protein due to a
      nonsense codon arising from the frameshift. Thus, these two mutant cell lines are
      deficient in the function of the ERCC1 gene for NER.

PMID- 9653454
TI  - Isolation and characterization of iridoviruses from the giant toad Bufo marinus
      in Venezuela.
AB  - In this communication we describe for the first time the isolation of 7
      iridoviruses from the toad Bufo marinus and an unknown species of frog
      Leptodactylus in Venezuela, South America. The viruses are icosahedral with
      electron-dense cores, each of which is surrounded by an inner membrane, capsid
      and a cell-derived envelope. The virus(es) have an average vertex to vertex
      diameter of 160 nm and replicate in the cytoplasm of a range of cell lines.
      Within the cytoplasm of infected cells, rarefied areas could be observed;
      structures lacked cellular organelles and contained complete, empty and
      developing viruses. Results from antigen-capture enzyme-linked immunosorbent
      assays (ELISA) with polyclonal antibody raised against epizootic haematopoietic
      necrosis virus (EHNV) indicated cross-reactivity between these isolates, Bohle
      iridovirus (BIV) and frog virus 3 (FV3). Comparison of polypeptide and genomic
      profiles indicated that the Venezuelan viruses shared many polypeptides of
      equivalent molecular weight with type species FV3. There were, however,
      differences between the group of Venezuelan viruses and FV3 and BIV. The viruses
      belongs to the family Iridoviridae and the genus Ranavirus.

PMID- 9653455
TI  - Taura syndrome of penaeid shrimp: cloning of viral genome fragments and
      development of specific gene probes.
AB  - The ssRNA genome extracted from purified Taura Syndrome Virus (TSV) was
      transcribed into double-stranded, blunt-ended cDNA and was used to construct cDNA
      libraries either in pUC 18 or in pBluescript II KS-vectors. Twelve recombinant
      plasmids chosen after screening of the libraries were subjected to restriction
      enzyme digestions for determination of size inserts and restriction maps. Two of
      them, pP15 and pQ1, were selected for probe construction. The inserts, 1500 and
      1300 base pairs (bp) respectively, were DIG-11dUTP-labelled and the corresponding
      probes were named P15 and Q1. On northern blots and dot blots, using different
      denaturation methods, the 2 probes hybridized specifically with extracted RNA-TSV
      genome, TSV and infected TS shrimp homogenates. No positive hybridization was
      obtained with other shrimp viruses tested [Infectious Hypodermal and
      Hematopoietic Necrosis Virus (IHHNV) and Hepatopancreatic Parvovirus (HPV)]. The
      specificity of the 2 probes was confirmed by in situ hybridization on
      histological sections of TS diseased shrimps.

PMID- 9653456
TI  - Virulence and antigenic characteristics of a cultured Rickettsiales-like organism
      isolated from farmed Atlantic salmon Salmo salar in eastern Canada.
AB  - The present study describes culture, virulence and antigenic characteristics of a
      Rickettsiales-like organism (RLO) associated with mortality in farmed Atlantic
      salmon in eastern Canada. Clinical disease was reproduced in naive Atlantic
      salmon parr by intraperitoneal i.p. inoculation with kidney homogenate from
      naturally infected fish. Pure cultures of RLO were isolated into chinook salmon
      embryo (CHSE) cells from kidney of experimentally infected fish. The RLO caused
      cytopathic effect in cultured CHSE-214 typified by coalescing areas of swollen
      cells that eventually detached from the substrate. Bacteria in infected culture
      supernatants reacted with Piscirickettsia salmonis-specific polyclonal sera or
      monoclonal antibody (MAb) in an indirect fluorescent antibody test. IP
      inoculation with cultured RLO resulted in mortalities of 100, 62, 22.5 and 0% in
      Atlantic salmon, coho salmon, rainbow trout and common carp, respectively.
      Cultured RLO were sensitive to chloramphenicol, flumequine, oxytetracycline and
      oxolinic acid and insensitive to gentamicin and amphotericin B. RLO antigens were
      compared with those of 3 strains of P. salmonis from Chilean salmon by SDS-PAGE
      and immunoblotting. A silver-staining band of about 12 kDa was detected in
      proteinase K (PK) digests of all RLO strains, and a diffuse band of about 15 kDa
      was observed in 2 Chilean strains only. No other silver-stained bands were
      visible in PK digests of any strain examined. The polyclonal serum recognized 9
      protein bands and multiple non-protein bands extending from less than 20 kDa to
      greater than 95 kDa in all isolates. The MAb reacted with an epitope in PK
      digests that occurred in all 4 strains on structures of widely ranging molecular
      masses, resulting in a ladder pattern similar to that obtained with polyclonal
      serum. Treatment of PK digests with periodic acid abolished reactivity with MAb
      and polyclonal serum. Co-elution of 2-keto-3-deoxyoctonate and MAb reactivity
      following size exclusion chromatography of solubilized P. salmonis suggested that
      the MAb recognized a lipopolysaccharide-associated epitope in all 4 RLO isolates.
      Cultural, virulence and antigenic similarities among the strains examined in the
      present study indicate that the eastern Canadian salmonid RLO should be
      considered a strain of P. salmonis.

PMID- 9653457
TI  - Pathology of Piscinoodinium sp. (Protozoa: Dinoflagellida), parasites of the
      ornamental freshwater catfishes Corydoras spp. and Brochis splendens (Pisces:
      Callichthyidae).
AB  - Piscinoodinium sp. (Protozoa, Dinoflagellida) was commonly found on routine
      smears of samples of Brochis splendens and Corydoras spp. imported into Britain
      from South America, and on samples of the same group of fish examined at the
      exporters' holding facilities in Brazil. Infected fish had trophonts of different
      sizes on the gills and skin. In histological sections of the skin, the trophonts
      were found to be attached within depressions of different depths or enclosed by
      hyperplastic epithelial cells. Such enclosed trophonts have not previously been
      reported. Since some of the enclosed trophonts were dead, it was thought that
      enclosure was a result of the deep penetration of the trophont and the host
      defence mechanism. On the gills the Piscinoodinium infection was commonly
      associated with epithelial hypertrophy, focal and diffuse hyperplasia, oedema of
      the respiratory epithelium and lamellar fusion. The presence of this protozoan on
      different species of fish from the same shipment suggests that the infection was
      acquired before export. The source of infection and the stages of the export
      process which expose the fish to the highest risk of infection are discussed.

PMID- 9653458
TI  - Oral pharmacological treatments for parasitic diseases of rainbow trout
      Oncorhynchus mykiss. I: Hexamita salmonis.
AB  - Various drugs were evaluated as regards efficacy for the treatment of Hexamita
      salmonis infection in rainbow trout. The results confirm the efficacy of
      nitroimidazoles: infection was completely eradicated not only by metronidazole
      (which has been recommended previously for the treatment of hexamitosis), but
      also by benznidazole, ronidazole and secnidazole, which have not been assayed
      previously. The non-nitroimidazoles albendazole, aminosidine, diethylcarbamazine
      and nitroscanate also completely eliminated infection. The remaining non
      nitroimidazoles tested (amprolium, bithionol, febantel, flubendazole, levamisole,
      netobimin, niclosamide, nitroxynil, oxibendazole, parbendazole, piperazine,
      praziquentel, tetramisole, thiophanate, toltrazuril, trichlorfon and
      triclabendazole) were not effective.

PMID- 9653459
TI  - In vitro cultivation and temperature-dependent growth of two strains of
      Spironucleus barkhanus (Diplomonadida: Hexamitidae) from Atlantic salmon Salmo
      salar and grayling Thymallus thymallus.
AB  - Spironucleus barkhanus from muscle abscesses of farmed Atlantic salmon Salmo
      salar L., and from the gall bladder of grayling Thymallus thymallus (L.) was
      cultivated axenically in a medium routinely used for cultivation of the human
      pathogen Giardia duodenalis. Trophozoites multiplied by binary division, but
      multinucleated cells (< 10 nuclei) were frequently observed. Complete cell
      divisions were never observed in these cells. Both strains grew at all
      temperatures tested (5, 10, 15 and 20 degrees C). However, continuous growth of
      the salmon strain at 20 degrees C was not possible. Growth potential, calculated
      as minimum generation time, showed relatively small differences both between
      strains and among temperatures, but the results indicate that the grayling strain
      had both a slightly higher optimum temperature and a higher upper temperature
      limit than the salmon strain.

PMID- 9653460
TI  - Systemic spironucleosis in sea-farmed Atlantic salmon Salmo salar, caused by
      Spironucleus barkhanus transmitted from feral Arctic char Salvelinus alpinus?
AB  - A hexamitid flagellate was found in the gall bladder and intestine of Arctic char
      Salvelinus alpinus in northern Norway. Scanning and transmission electron
      microscopy showed this flagellate to be identical to Spironucleus barkhanus from
      grayling Thymallus thymallus and farmed Atlantic salmon Salmo salar. It is
      hypothesized that systemic spironucleosis in sea-caged Atlantic salmon was due to
      transmission of flagellates from feral char to the salmon.

PMID- 9653461
TI  - Generation and preliminary characterization of monoclonal antibodies directed to
      glycerophospholipid:cholesterol acyltransferase (GCAT) native epitopes of
      Aeromonas salmonicida.
AB  - Four monoclonal antibodies (MAbs) directed to native
      glycerophospholipid:cholesterol acyltransferase (GCAT) epitopes of Aeromonas
      salmonicida were isolated using an esterase capture assay. The molecular mass of
      this MAb-defined antigen was estimated to be 26 kDa in SDS-PAGE. Three different
      epitope specificities of these MAbs were demonstrated. It was shown that all 4
      MAbs recognize GCAT in culture filtrates of the strain MT004 excluding the
      simultaneous trapping of other components. None of the MAbs react with the
      denatured GCAT in Western blots.

PMID- 9653462
TI  - Mammographic appearance of the breasts during pregnancy and lactation: false
      assumptions.
AB  - RATIONALE AND OBJECTIVES: It is believed that pregnant and lactating women have
      dense breasts, thereby limiting the usefulness of mammography. To our knowledge,
      no reports have been published on this topic for nearly 4 decades. The purpose of
      our study was to determine whether this assumption is accurate given current
      state-of-the-art mammography. MATERIALS AND METHODS: Mammograms of 18 women (six
      pregnant, seven lactating, and five who recently discontinued lactation) were
      examined and compared with their baseline (before pregnancy or lactation)
      mammograms and with mammograms of 18 age-matched control subjects. Studies were
      scored for breast density according to the Breast Imaging Reporting and Data
      System and evaluated for change in density and size. RESULTS: Three of the six
      pregnant women had unchanged breast density compared with baseline studies and
      had scattered fibroglandular or heterogeneously dense tissue. Of the three
      without baseline studies, one had extremely dense, one had heterogeneously dense,
      and one had scattered fibroglandular tissue. All seven lactating women had either
      heterogeneously dense or extremely dense tissue. The breast tissue in four was
      unchanged in density and increased in two; no baseline study was available for
      the remaining patient. Seven studies in five women who had discontinued lactation
      1 week to 5 months prior to mammography showed no change in density compared with
      baseline. CONCLUSION: Pregnant and lactating women do not always have dense
      breasts, and mammography can be performed without substantial concern for the
      limitations of breast density. Mammography can be as useful in these women as it
      is in other women with breast signs and symptoms.

PMID- 9653463
TI  - Predictive model for the diagnosis of intraabdominal abscess.
AB  - RATIONALE AND OBJECTIVES: The authors investigated the use of an artificial
      neural network (ANN) to aid in the diagnosis of intraabdominal abscess. MATERIALS
      AND METHODS: An ANN was constructed based on data from 140 patients who underwent
      abdominal and pelvic computed tomography (CT) between January and December 1995.
      Input nodes included data from clinical history, physical examination, laboratory
      investigation, and radiographic study. The ANN was trained and tested on data
      from all 140 cases by using a round-robin method and was compared with linear
      discriminate analysis. A receiver operating characteristic curve was generated to
      evaluate both predictive models. RESULTS: CT examinations in 50 cases were
      positive for abscess. This finding was confirmed by means of laboratory culture
      of aspirations from CT-guided percutaneous drainage in 38 patients, ultrasound
      guided percutaneous drainage in five patients, surgery in five patients, and
      characteristic appearance on CT scans without aspiration in two patients. CT
      scans in 90 cases were negative for abscess. The sensitivity and specificity of
      the ANN in predicting the presence of intraabdominal abscess were 90% and 51%,
      respectively. Receiver operating characteristic analysis showed no statistically
      significant difference in performance between the two predictive models.
      CONCLUSION: The ANN is a useful tool for determining whether an intraabdominal
      abscess is present. It can be used to set priorities for CT examinations in order
      to expedite treatment in patients believed to be more likely to have an abscess.

PMID- 9653464
TI  - Hysterosalpingography with videofluoroscopy: effect on radiologic practice in an
      academic medical center.
AB  - RATIONALE AND OBJECTIVES: The authors attempted to determine whether videotaping
      the fluoroscopic portion of hysterosalpingography would result in changed
      diagnoses or an increase in diagnostic confidence. MATERIALS AND METHODS: Ninety
      nine consecutive outpatients underwent routine hysterosalpingography. The
      fluoroscopic portion of the examination was captured on videotape. Two
      consecutive interpretations of each hysterosalpingogram were made by attending
      radiologists. First, spot radiographs were interpreted alone. Second, these
      images were viewed along with videofluoroscopy. Concordance of and confidence in
      findings for the two interpretations were assessed with the two-tailed Fisher
      exact test. RESULTS: Interpretations of spot radiographs alone and with
      videofluoroscopy were in agreement in 92 of 99 uterine examinations and 164 of
      198 tubal examinations. For uterine examinations classified as normal,
      interpretations of spot radiographs and videofluoroscopy were in agreement in 56
      of 57 cases; there was no change in confidence with review of videofluoroscopic
      images. For uterine examinations interpreted as abnormal, agreement was noted in
      36 of 42 cases (P = .04), and confidence increased with videofluoroscopy in 10 of
      42 cases (P = .00001). With normal tubal findings, interpretations agreed in 94
      of 118 cases, and confidence increased in 56 of 118 cases (P = .002). With
      abnormal tubal findings, interpretations agreed in 70 of 80 cases, and confidence
      increased in 20 of 80 cases (P = .002). When findings with and without
      videofluoroscopy were discordant, confidence was always higher after review of
      video-fluoroscopic images. CONCLUSION: Review of videofluoroscopic images
      obtained during hysterosalpingography increases the accuracy and confidence of
      diagnoses compared with review of spot radiographs alone.

PMID- 9653465
TI  - Educational outreach to mammography facility staff to assist with compliance with
      the Mammography Quality Standards Act in rural North Carolina.
AB  - RATIONALE AND OBJECTIVES: The purpose of this project was to develop and evaluate
      an educational program targeted at mammography facilities in rural areas of North
      Carolina that were having difficulty complying with the 1992 Mammography Quality
      Standards Act (MQSA). MATERIALS AND METHODS: Fourteen facilities deemed at risk
      for closure under MQSA were identified by state inspection personnel. Problems at
      the facilities were evaluated by a radiologist, a physicist-educator, and a
      radiation physicist through a written survey, review of phantom and clinical
      images, and a site visit. Individual advice and instruction were provided on-site
      by the physicist-educator, with written materials provided in follow-up. A repeat
      site visit was made 4-6 months after the initial visit. RESULTS: Of 51 problems
      identified at the 12 institutions that completed the program, 35 (69%) were
      corrected. All facilities that had failing phantom scores at the inspection prior
      to the intervention had passing scores at the inspection after the intervention.
      There was a statistically significant increase in the sum of the phantom scores
      for the facilities offered this intervention compared with those not offered it
      (P = .03). CONCLUSION: This educational program improved mammography quality at
      participating facilities.

PMID- 9653466
TI  - Pharmacokinetics of gadodiamide injection in patients with severe renal
      insufficiency and patients undergoing hemodialysis or continuous ambulatory
      peritoneal dialysis.
AB  - RATIONALE AND OBJECTIVES: The authors performed this study to evaluate the
      pharmacokinetics, dialysability, and safety of gadodiamide injection in patients
      with severely reduced renal function not treated with renal replacement therapy
      and patients undergoing hemodialysis or continuous ambulatory peritoneal
      dialysis. MATERIALS AND METHODS: Twenty-seven patients--nine with severely
      reduced renal function (glomerular filtration rate, 2-10 mL/min), nine undergoing
      hemodialysis, and nine undergoing continuous ambulatory peritoneal dialysis--were
      followed up for 5, 8, and 22 days, respectively, after receiving gadodiamide
      injection (0.1 mmol per kilogram body weight). RESULTS: Gadodiamide injection
      caused no changes in renal function. In patients with severely reduced renal
      function, the elimination half-life of gadodiamide injection was prolonged (34.3
      hours +/- 22.9) compared with data in healthy volunteers (1.3 hours +/- 0.25). An
      average of 65% of the gadodiamide injected was eliminated during a hemodialysis
      session. After 22 days of continuous ambulatory peritoneal dialysis, 69% of the
      total amount of gadodiamide was excreted; this reflects the low peritoneal
      clearance. In all patients, no metabolism or transmetallation of gadodiamide was
      found. There were no contrast material-related adverse events. CONCLUSION:
      Gadodiamide is dialysable and can safely be used in patients with severely
      impaired renal function or those undergoing hemodialysis or continuous ambulatory
      peritoneal dialysis. No precautions to increase the elimination are necessary.

PMID- 9653467
TI  - Detection of pulmonary emboli at the segmental and subsegmental level with
      electron-beam CT: validation in a porcine model.
AB  - RATIONALE AND OBJECTIVES: The authors evaluated the sensitivity of electron-beam
      computed tomography (CT) in the detection of segmental and subsegmental pulmonary
      artery emboli in a porcine model. MATERIALS AND METHODS: Twenty-one segmental and
      subsegmental branch pulmonary arteries in five swine were selectively
      catheterized and embolized with gelatin sponge pledgets. The presence of emboli
      was confirmed by means of contrast material-enhanced angiography. Contrast
      enhanced CT scans of the pulmonary arteries were then obtained with 3-mm
      collimation, 2-mm table travel between sections, and an imaging time of 100 msec
      per section. Contrast material was injected at a rate of 2-3 mL/sec, depending on
      the animal's weight, with a total dose of 60 mL for each scan. Cardiac-gated and
      nongated scans were obtained, but breath holding was not possible in these
      animals. RESULTS: Contrast-enhanced electron-beam CT scanning allowed correct
      prospective identification of 18 of 21 emboli in the segmental and subsegmental
      branches of the pulmonary arteries. The overall sensitivity was 86%. Cardiac
      gating subjectively improved image quality but did not result in greater
      sensitivity in the detection of emboli. The level of sensitivity was not affected
      by the use of breath holding. CONCLUSION: Contrast-enhanced electron-beam CT is a
      sensitive method for the detection of embolism in the segmental and subsegmental
      pulmonary arteries.

PMID- 9653468
TI  - Current status of musculoskeletal radiology fellowships in the United States.

PMID- 9653469
TI  - Advanced breast biopsy instrumentation: a critique.

PMID- 9653470
TI  - MINDscape and PubMed: Web sites that can change the way we work.

PMID- 9653471
TI  - A protocol for management of a catastrophic complication of functional endoscopic
      sinus surgery: internal carotid artery injury.
AB  - Injury to the cavernous portion of the internal carotid artery is a well
      recognized and dreaded complication of functional endoscopic sinus surgery.
      Little information, however, has been presented in the Otolaryngology literature
      regarding the etiology, prevention, or treatment of this complication. The
      purpose of this study is to present a case report of a cavernous carotid artery
      injury during functional endoscopic sinus surgery. Relevant anatomy, preventive
      measures, and treatment approaches are discussed for this difficult problem.

PMID- 9653472
TI  - Interobserver variations in assessment of antral disease from direct sinoscopic
      observations compared to video recordings.
AB  - We tested the reliability of visual clinical sinoscopic observations by using
      video recordings. An edited video tape was made from the video-recorded bilateral
      antral sinoscopies of nine patients included in a prospective case series of
      inflammatory maxillary sinus disease in critically ill patients. An expert panel
      of four consultant ENT surgeons made individual appraisals of the video using a
      structured form. They had only been informed in general about the study, but had
      no further case knowledge in order to avoid all biases. Concordance and
      interobserver variabilities in the expert panel were compared in pairs. The
      assessments of the expert panel were compared with the observations of the
      performer, who was biased through individual case knowledge. Nine patients,
      either nasotracheally intubated or tracheotomized, had ventilator treatment for
      more than 7 days. One ENT surgeon performed all sinoscopies and made the direct
      observations. Satisfactory agreement was found on mucosal alterations. The
      concordance of recognizing bacterial infection was almost perfect. However, the
      assessment of redness from a video recording displayed only chance agreement. The
      differences between kappa statistic values within the expert panel group compared
      to the comparisons of performer versus expert panel were not significant. The
      case knowledge of the sinoscopist did not alter the assessments markedly and thus
      seemed only to have minor influence. Video recording as a method for second
      opinion was shown to be a useful technique, but will have to be further
      developed.

PMID- 9653473
TI  - Usefulness of patient symptoms and nasal endoscopy in the diagnosis of chronic
      sinusitis.
AB  - The diagnosis of chronic sinusitis can be difficult due to the variety and lack
      of specificity of presenting symptoms. Sinus CT scanning is presently considered
      the most sensitive and specific diagnostic method, but is expensive. In order to
      determine whether a combination of patient symptoms and nasal endoscopy could be
      used to predict which patients would have CT evidence of chronic sinusitis, we
      conducted a prospective study in which 92 consecutive patients referred for
      chronic sinusitis were required to fill out a questionnaire detailing their
      symptoms. Their responses were then correlated with subsequent findings on nasal
      endoscopy and CT scanning. Briefly, we found that patients with headache or
      facial pain as their chief complaint were less likely to have evidence of
      sinusitis than patients whose chief complaint was nasal obstruction or postnasal
      drip. Also, nasal endoscopy was shown to be moderately sensitive and highly
      specific in predicting results of CT scanning.

PMID- 9653474
TI  - Intracranial complications of sinusitis: a pediatric series.
AB  - Intracranial complications of sinusitis (ICS) (cerebral, epidural, and subdural
      abscesses, meningitis, and dural sinus thrombophlebitis) remain a challenging and
      contemporary topic. The progressive pneumatization and continued development of
      the sinuses after birth and the late appearance of the frontal and sphenoid
      sinuses imply that some infections would not appear until later childhood. We
      reviewed the records at a large pediatric hospital between 1986 and 1995 and
      found 10 children with 13 ICS (cerebral abscess, 5; extra-axial empyema, 5; and
      meningitis, 3). Of 43 children with cerebral abscess and 16 with extra-axial
      abscesses treated in this period, 12% of cerebral and 63% of extra axial
      abscesses were due to a sinogenic source. Multiple intracranial and extracranial
      complications of sinusitis in a single patient were common. The average age of
      children with ICS was 12.2 years old. We present these 10 cases and discuss their
      presentation, microbiology, and clinical course. Although the majority presented
      with a classic picture of headache, altered mental status, and fever, a few had
      symptoms that were more subtle. One child had recurrent meningitis, believed to
      be due to skull base dehiscence after endoscopic sinus surgery (ESS). He has
      required multiple otolaryngologic and neurosurgical procedures in an effort to
      prevent further episodes of meningitis. Ultimately, nine of 10 patients survived
      with an average hospital stay of 27.8 days (median of 17 days). The diagnosis of
      ICS requires a high index of suspicion, imaging of the brain and paranasal
      sinuses, and aggressive intervention.

PMID- 9653475
TI  - Endoscopically guided frontal sinus beclomethasone instillation for refractory
      frontal sinus/recess mucosal edema and polyposis.
AB  - Despite its metabolic complications, systemic corticosteroid therapy remains a
      mainstay in the treatment of refractory polyposis after endoscopic frontal
      sinusotomy. Furthermore, topical nasal corticosteroids often fail, presumably due
      to the relatively small dosage actually absorbed by the polyps. In order to
      minimize steroid complications while increasing the locally absorbed dose,
      beclomethasone (approximately 1 cc, 84 mcg/100 microliters) was instilled under
      endoscopic guidance directly into the frontal sinus in 31 instances in 16
      patients with postoperative frontal recess/sinus polyposis and mucosal edema. The
      frontal recess/sinus polyposis/edema resolved completely in 9 frontal sinuses,
      improved considerably in 7 frontal sinuses, improved minimally in 5 frontal
      sinuses, and remained unchanged in 10 frontal sinuses. No complications were
      noted. AM cortisol levels remained in the normal range. Endoscopically guided
      frontal sinus beclomethasone instillation should be considered for the treatment
      of refractory postoperative frontal sinus/recess polyposis/edema. Further basic
      and clinical research into the pathophysiology of the nasal mucosa is also
      warranted.

PMID- 9653476
TI  - Efficacy of an aqueous and a powder formulation of nasal budesonide compared in
      patients with nasal polyps.
AB  - Nasal polyps are commonly treated surgically. Intranasal administration of
      topical corticosteroids has gained increased acceptance as a treatment
      alternative. The aim of our study was to compare the efficacy of treatment of two
      formulations of budesonide with placebo on nasal polyps. At four Danish clinics
      138 patients suffering from moderate or severe nasal polyps were randomized to a
      twice daily treatment with Rhinocort Aqua 128 micrograms, Rhinocort Turbuhaler
      140 micrograms or placebo (Astra Draco, Sweden) for 6 weeks. Polyp size (primary
      efficacy variable), nasal symptoms, sense of smell, and patients' overall
      evaluation of treatment of efficacy were assessed by scores. Polyp size was
      reduced significantly in both budesonide treated groups compared with placebo,
      but there was no statistical difference between the two actively treated groups.
      Patients' nasal symptom scores was significantly more reduced in the Aqua
      compared to the Turbuhaler treated group, and both reduced symptom scores were
      significantly better compared to placebo. Sense of smell was significantly
      improved in the actively treated groups compared to placebo. The proportion of
      patients rating substantial or total control over symptoms after 6 weeks
      treatment was 60.9% and 48.2% in the Aqua and Turbuhaler-treated groups,
      respectively, which was significantly better compared with 29.8% in the placebo
      treated group. Rhinocort Aqua and Rhinocort Turbuhaler were equally well
      tolerated.

PMID- 9653477
TI  - Frontoethmoidectomy with Sewall-Boyden reconstruction: alive and well, a 25-year
      experience.
AB  - Recent controversies in the rhinologic literature regarding surgical management
      of the frontal sinus center around relatively new techniques using endoscopic
      intranasal approaches. Few authors have addressed the concept of frontal "duct"
      reconstitution, relying instead upon variations of the stenting concept, which
      fail at least 30% of the time. Some oral presentations and discussions in the
      past have gone so far as to say that external frontoethmoidectomy is an
      antiquated operation with few indications. One reason for its recent disfavor
      concerns the reported high rate of postoperative naso-frontal drainage track
      stenosis leading to recurrent disease. The senior author has a 25-year experience
      with a frontal recess reconstruction technique known as the Sewall-Boyden flap.
      This technique, coupled with the frontoethmoidectomy approach, has been effective
      with a low failure rate in 41 cases. This article serves to remind sinus surgeons
      of a safe, effective technique for establishing a drainage track from the frontal
      sinus: external fronto-ethmoidectomy with Sewall-Boyden flap reconstruction.

PMID- 9653478
TI  - The evaluation of ciliary function: electron versus light microscopy.
AB  - Diagnosing Primary Ciliary Dyskinesia can often be difficult. Physical findings
      suggest the disease, but definitive diagnosis should be made with a ciliary
      biopsy. Twenty biopsies were obtained from 16 patients and all underwent both
      light and electron microscopic examination. In 8/20 (40%) there was a discrepancy
      between the different imaging techniques. Therefore, light microscopy should be
      used to assess adequacy of biopsy and motion of the cilia along with electron
      microscopy to examine ultrastructure.

PMID- 9653479
TI  - Muscarinic ciliostimulation requires endogenous prostaglandin production.
AB  - Prostaglandin E2 (PGE2) is a known modulator in upper airway ciliary activity and
      may be involved in the transduction of the muscarinic acetylcholine receptor
      signal. We studied the in vitro effects of muscarinic ciliostimulation on ciliary
      beat frequency (CBF) and PGE2 in human adenoid explants to determine whether PGE2
      production is an essential step in the signal transduction mechanism.
      Methacholine applied to adenoid explants significantly increased ciliary beat
      frequency. This effect was blocked by the application of diclofenac, a
      cyclooxygenase inhibitor. Using radioimmunoassay, PGE2 production was measured
      during ciliostimulation with methacholine. Methacholine produced a significant
      increase in production in PGE2 during ciliostimulation. The roles of
      phospholipase C and phospholipase A2 in prostaglandin production were
      investigated by inhibiting these enzymes. D609, a phospholipase C inhibitor,
      significantly inhibited ciliary beat frequency increase and PGE2 production
      during methacholine stimulation. However, PACOCF3, a phospholipase A2 inhibitor,
      did not block ciliary beat frequency increase or PGE2 production in response to
      methacholine. These data show that phospholipase C is required for PGE2
      production and ciliostimulation.

PMID- 9653480
TI  - Subjective comparison of Nd:YAG, diode, and CO2 lasers for endoscopically guided
      inferior turbinate reduction surgery.
AB  - Lasers using different wavelengths and delivery systems have been used to reduce
      the inferior turbinate mass when hypertrophic inferior turbinates obstruct the
      nasal airway. Different laser systems produce different laser-tissue
      interactions. This study presents a comparison between three laser systems: CO2,
      Nd:YAG, and Diode lasers for inferior turbinate reduction surgery, all performed
      under endoscopic control. A total of 46 patients were randomized into three
      treatment groups and followed for more than 1 year. Subjective and objective data
      were collected. Subjective impressions of improved nasal airway was achieved in
      41% (Diode), 47% (Nd:YAG) and 57% (CO2) and was not statistically significant.
      There was more postoperative bleeding in the CO2 laser group, with 3 patients
      requiring tamponade. The CO2 laser procedure also took longer to perform. These
      results failed to show a significant difference between the different lasers for
      inferior turbinate reduction. Overall, the results were not impressive.

PMID- 9653481
TI  - Correction of the twisted nose deformity: a surgical algorithm using the external
      rhinoplasty approach.
AB  - Successful correction of the twisted nose is challenging due to the complex
      nature of the underlying anatomic deformity. Although the literature has in
      general supported endonasal rhinoplasty techniques for the twisted nose, we
      propose a surgical algorithm using the external rhinoplasty approach. The
      algorithm offer a stepwise, structured method that is adaptable to individual
      variations in anatomic deformity. The advantages and relative disadvantages of
      the external rhinoplasty approach are discussed, and a clinical experience of 30
      patients is reviewed. Application of the external rhinoplasty algorithm in
      correction of the twisted nose can yield consistently satisfactory functional and
      aesthetic results.

PMID- 9653482
TI  - The versatile autogenous rib graft in septorhinoplasty.
AB  - In the graft depleted revision rhinoplasty patient and the patient with major
      tissue needs, alternatives to septal and conchal cartilage grafts are needed. The
      costal cartilage graft and rib bone/costal cartilage combination graft are
      excellent alternatives. In this study 14 patients received 40 grafts from 20
      autogenous ribs harvested during septorhinoplasty. Materials were harvested for
      use as septal replacement grafts, cantilevered grafts, dorsal onlay grafts,
      columellar struts, and tip grafts. Patient followup was 6 to 31 months, and no
      evidence of graft resorption or warpage was evident during that period.
      Complications of harvest were minimal, and harvest techniques are detailed.

PMID- 9653483
TI  - Once more in St. Gallen.

PMID- 9653484
TI  - HCV and lymphoproliferative diseases.

PMID- 9653485
TI  - Enhancing the therapeutic index of concomitant chemoradiotherapy for head and
      neck cancer.

PMID- 9653486
TI  - Cost-effectiveness analysis in oncology.
AB  - Physicians are faced with a burgeoning literature of economic studies. However,
      most physicians have little training in evaluating economic research. Economic
      studies involve a comparison of the costs and benefits of alternative treatment
      options. To be of use for medical decision making, they should meet appropriate
      methodological standards. These include clear specification of the research
      question and the perspective from which the study is being undertaken, comparison
      of relevant treatment options, identification and quantification of all important
      costs and benefits, the use of discounting to allow for time preferences for
      costs and benefits, and sensitivity analyses to test the robustness of the
      study's results. Unfortunately, not all adhere to these principles. Physicians
      need to be able to understand and critically assess the quality of economic
      studies, and the applicability of the results to their own situation, in order to
      participate in medical policy decisions.

PMID- 9653487
TI  - Randomized controlled trials in cancer: improving the quality of their reports
      will also facilitate better conduct.
AB  - There has been a renewed interest in ways to help improve the quality of reports
      of clinical trials recently. In this paper we describe these developments. This
      work has also focused increased attention on how clinical trials are planned and
      executed. Some common problems are reviewed and suggestions for improving their
      conduct are also discussed.

PMID- 9653488
TI  - Adding adjuvant CMF chemotherapy to either radiotherapy or tamoxifen: are all
      CMFs alike? The International Breast Cancer Study Group (IBCSG).
AB  - The first reported effective adjuvant combination regimen for patients with
      operable breast cancer comprised oral cyclophosphamide (C) days 1-14 with
      intravenous methotrexate (M) and fluorouracil (F) on days 1 and 8, repeated every
      28 days ('classical' CMF). These drugs have since been extensively used with or
      without endocrine therapies and/or other cytotoxics, as well as with radiation
      therapy to the chest wall yielding conflicting results. Although doses and
      schedules have varied widely, the combination of these three drugs has been
      generically referred to as CMF. Evidence exists that reducing the dose and/or
      altering the schedule of CMF ('modified' CMF) have compromised its efficacy in
      metastatic breast cancer. Reduction below standard dose of a similar regimen also
      gave inferior results in the adjuvant setting. In fact, the recently reported
      improved outcome of adding radiation therapy to CMF was only demonstrated in
      comparisons with a 'modified' CMF. Furthermore, trials in women with estrogen
      receptor-positive breast cancer, which did not demonstrate any significant
      benefit for the addition of adjuvant CMF to tamoxifen compared with tamoxifen
      alone, also used 'modified' CMF. Therefore, adherence to the 'classical' dose and
      schedule is recommended when CMF is used in adjuvant therapy.

PMID- 9653489
TI  - Clinico-pathological characterization of hepatitis C virus-related B-cell non
      Hodgkin's lymphomas without symptomatic cryoglobulinemia.
AB  - BACKGROUND: Epidemiological evidence has suggested an association between
      hepatitis C virus (HCV) infection and B-cell lymphoproliferation. We studied the
      prevalence of HCV infection in a series of de novo B-cell non-Hodgkin's lymphoma
      (B-NHL) cases and correlated virological findings with clinico-histological
      features. PATIENTS AND METHODS: One hundred fifty-seven patients with de novo B
      NHL were included in the study. Their serum was examined by ELISA and RIBA for
      the presence of anti-HCV antibodies, and either the peripheral blood mononuclear
      cells or the pathology tissues of all of the patients were examined by reverse
      transcriptase polymerase chain reaction for the presence of HCV RNA sequences.
      RESULTS: HCV infection occurred in 22.3% of B-NHL patients and was documented
      before the diagnosis in about half of the positive cases. Of interest, HCV
      infection was more frequently found in follicular center, marginal zone and
      diffuse large-cell lymphoma types, but was not associated with symptomatic
      cryoglobulinemia. The median survival time was 48 months in HCV-positive and 52
      months in HCV-negative B-NHL patients. CONCLUSIONS: Our findings strengthen the
      pathogenetic link between HCV and B-NHL and show that HCV infection may be
      associated with the malignant proliferation of defined B-cell subsets other than
      the immunoglobulin Mk B-cell subset involved in the pathogenesis of mixed
      cryoglobulinemia type II and associated lymphoplasmacytoid lymphoma type. HCV
      related liver disease did not affect the survival of our B-NHL patients.

PMID- 9653490
TI  - Impact of hepatitis C virus infection on clinical features, quality of life and
      survival of patients with lymphoplasmacytoid lymphoma/immunocytoma.
AB  - BACKGROUND: The non-Hodgkin's lymphoma (NHL) subgroup most frequently associated
      with hepatitis C virus (HCV) infection is the lymphoplasmacytoid
      lymphoma/immunocytoma (Lp-Ic). We have assessed the impact of the infection on
      the clinical features, quality of life and survival of HCV+ve Lp-Ic patients as
      compared to its impact in HCV-ve patients. PATIENTS AND METHODS: Seventy patients
      with Lp-Ic consecutively observed over a six-year period were studied. Clinical,
      virological and histopathological features were recorded at diagnosis. Quality of
      life was assessed using a scoring system including disease-related symptoms,
      performance status, working ability, hospital admissions and therapies required.
      RESULTS: Eighteen patients (26%) with HCV infection were identified. Significant
      differences between those patients and the HCV-ve group included number of
      symptomatic patients, Hb levels, serum protein levels, entity of the IgM
      monoclonal component, number of patients with cryoglobulins and with organ
      (liver, kidney) involvement, and entity and pattern of bone marrow infiltration.
      Survival rates were similar (P = 0.8383), but the quality-of-life score was
      significantly worse for the HCV+ve patients (P = 0.002). All anti-HCV Ab+ve
      patients tested positive for HCV RNA; genotype 2ac was detected in a significant
      proportion of cases. CONCLUSIONS: This study confirms that HCV infection is
      present in about one-third of patients with Lp-Ic. HCV infection does not seem to
      affect the overall survival of patients with Lp-Ic, but it affects the clinical
      expression of the disease, so that the overall quality of life of HCV+ve patients
      is significantly worse.

PMID- 9653491
TI  - Selective cytoprotection with amifostine in concurrent radiochemotherapy for head
      and neck cancer.
AB  - BACKGROUND: Amifostine has reduced toxicities associated with radiation therapy
      and platinum-based chemotherapy. In a phase II randomized trial, we investigated
      the ability of amifostine to reduce the toxicity of carboplatin plus radiotherapy
      (RCT) in patients with head and neck cancer. PATIENTS AND METHODS: Thirty-nine
      patients with stage III or IV squamous cell carcinomas of the head and neck
      received RCT (following surgery or as primary treatment). Radiotherapy was given
      five days per week with daily fractions of 2 Gy, up to a total dose of 60 Gy in
      conjunction with carboplatin 70 mg/m2 on days 1 through 5 and days 21 through 26.
      Eligible patients were randomised to receive RCT alone or preceded by a rapid
      infusion of amifostine (500 mg) on the days when carboplatin was administered.
      RESULTS: Patients receiving amifostine + RCT (n = 25) had significantly reduced
      mucositis (P = 0.0001) and xerostomia (P = 0.0001) in comparison with patients
      receiving RCT alone (n = 14). Additionally, patients receiving amifostine + RCT
      had significantly less thrombocytopenia (P = 0.001) and leukopenia (P = 0.001).
      At 12 months following therapy, 79% of patients receiving amifostine + RCT had no
      evidence of disease compared with 64% of those receiving RCT alone. CONCLUSIONS:
      Amifostine reduces the RCT-induced toxicities in patients with head and neck
      cancer and has no negative impact on antitumour efficacy.

PMID- 9653492
TI  - Alternating triple therapy for the treatment of intermediate grade and
      immunoblastic lymphoma.
AB  - BACKGROUND: CHOP is currently considered the gold standard of treatment for
      intermediate grade lymphomas. We designed a new regimen known as 'ATT'
      (alternating triple therapy) which uses three non-cross resistant combinations in
      alternating sequence for nine cycles. MATERIALS AND METHODS: This is a phase II
      clinical trial with comparison to CHOP/CMED historical controls using prognostic
      factors. The tumor score system was used to evaluate the results of this trial.
      Two hundred sixty-eight eligible patients who had one or more of the following
      adverse features: bulky disease, elevated LDH or > 1 extranodal site were
      analyzed. Outcome measures consist of survival and failure free survival.
      RESULTS: At a median follow-up of 32 months, there was no statistically
      significant difference in survival for those with favorable prognostic factors
      (tumor score < or = 2). However, there was a statistically significant difference
      in favor of ATT for those with unfavorable tumor scores. When we examined the
      failure-free survival of those with unfavorable tumor scores, we again observed a
      superiority for the ATT regimen over CHOP/CMED but the opposite was true for
      those with favorable tumor scores. We also found a statistically significant
      difference in favor of the ATT regimen when compared with CHOP/CMED for patients
      < or = 60 years old with a tumor score > or = 3, while no advantage was found for
      those > 60 years. CONCLUSIONS: ATT appears more effective but only for patients <
      60 years old with unfavorable tumor scores. In those older than 60 years with
      favorable tumor score, CHOP/CMED appears superior. ATT might be an adequate
      regimen for young patients with poor prognostic features while CHOP/CMED might be
      a better choice for those with good prognosis irrespective of age. For those > 60
      years with unfavorable tumor scores neither ATT or CHOP/CMED were adequate
      treatment. Because of the phase II nature of this study, these conclusions should
      be considered as hypotheses which require prospective testing.

PMID- 9653493
TI  - Application of interphase cytogenetics for the detection of t(11;14)(q13;q32) in
      mantle cell lymphomas.
AB  - BACKGROUND: The chromosomal translocation t(11;14)(q13;q32) is the hallmark of
      mantle cell lymphoma (MCL) in which it can be detected cytogenetically in about
      75% of cases. The t(11;14) translocation juxtaposes the bcl-1 locus in chromosome
      band 11q13 next to the IgH locus in chromosome band 14q32 and, thus, leads to
      deregulation of the cell cycle regulatory protein cyclin D1, which is encoded by
      the CCND1 gene localized at the telomeric border of the bcl-1-locus. MCL has the
      worst prognosis of all low-grade non-Hodgkin's lymphomas (NHL). In some
      instances, however, histopathologic differentiation between MCL and other low
      grade B-cell NHL is difficult. Therefore, detection of the t(11;14) translocation
      is of essential diagnostic value for the risk-adjusted management of patients
      with MCL. Unfortunately, chromosome analyses are frequently hampered by the low
      yield and quality of tumor metaphases. As the 11q13 breakpoints are scattered
      over a region of more than 120 kb the application of molecular genetic techniques
      is also limited. PATIENTS AND METHODS: We established an interphase fluorescence
      in situ hybridization (FISH) approach for the detection of the t(11;14)
      translocation by use of a cosmid probe hybridizing to the IgH constant region and
      a YAC spanning the bcl-1 region. Cells containing a t(11;14) translocation show a
      colocalisation of the signals for IgH and bcl-1. Eight control samples and 15 MCL
      specimens were investigated. RESULTS: According to our control studies, samples
      containing more than 10% of cells with this signal constellation can be diagnosed
      as carrying a clonal t(11;14) translocation. All eleven MCL found to carry the
      t(11;14) translocation by chromosome analysis were positive in our FISH assay.
      Additionally, two of four MCL lacking a clonal t(11;14) translocation by
      chromosome analysis were shown to carry this aberration in 14% and 37% of
      interphase nuclei. Southern blot data indicate that our FISH assay reliably
      detects the t(11;14) translocation irrespective of the location of the
      breakpoints within the bcl-1 region. CONCLUSIONS: The described interphase FISH
      assay provides a reliable and routinely applicable tool for diagnosis of the
      t(11;14) translocation.

PMID- 9653494
TI  - Feasibility and pharmacokinetic study of a chimeric anti-CD20 monoclonal antibody
      (IDEC-C2B8, rituximab) in relapsed B-cell lymphoma. The IDEC-C2B8 Study Group.
AB  - BACKGROUND: In clinical trials in the USA, IDEC-C2B8 (a mouse-human chimeric anti
      CD20 monoclonal antibody) has demonstrated high response rates with only mild
      toxic effects in relapsed B-cell lymphoma at a dose of four weekly 375 mg/m2
      infusions. The aim of the present trial was to determine whether or not this dose
      is practically applicable to Japanese patients with relapsed B-cell lymphoma with
      respect to safety, pharmacokinetics and efficacy. PATIENTS AND METHODS: Patients
      with relapsed CD20+ B-cell lymphoma received intravenous infusions of IDEC-C2B8
      once a week for four weeks. A total of 12 patients (four at 250 mg/m2 and eight
      at 375 mg/m2) were enrolled. RESULTS: All 11 eligible patients treated with
      either dose level tolerated IDEC-C2B8 well. Commonly observed adverse drug
      reactions were grades 1 or 2 non-hematologic toxicities during the infusion,
      consisting mostly of flu-like symptoms and skin reactions. All of the observed
      hematologic toxicities were of grade 3 or less, and transient. A rapid and
      sustained B-cell decrease in peripheral blood was observed, but no infectious
      episodes were encountered. Human anti-mouse and anti-chimeric antibodies were not
      detected. Of the 11 eligible patients (eight with follicular, two with diffuse
      large-cell and one with mantle cell lymphoma), two showed a complete response and
      five showed a partial response, and all of the seven responders had lymphoma with
      follicular histology. A pharmacokinetic analysis showed that the elimination half
      life (T1/2) of IDEC-C2B8 was 445 +/- 361 hours, and that the serum antibody
      levels increased in parallel with the course of infusions, and in most patients
      was still measurable at three months. CONCLUSIONS: The dose of four weekly 375
      mg/m2 infusions of IDEC-C2B8 is safe and effective in Japanese patients with
      relapsed B-cell lymphoma. Further studies evaluating IDEC-C2B8 are warranted.

PMID- 9653495
TI  - The impact of adding low-dose leucovorin to monthly 5-fluorouracil in advanced
      colorectal carcinoma: results of a phase III trial. Swiss Group for Clinical
      Cancer Research (SAKK).
AB  - PURPOSE: A wide variety of fluorouracil (FU)-plus-leucovorin (LV) dose schedules
      are in clinical use for the treatment of advanced colorectal cancer. Only the
      monthly low-dose LV-plus-FU regimen, as used by the North Central Cancer
      Treatment Group, has demonstrated a lasting survival benefit as opposed to FU
      alone (J Clin Oncol 1989; 7: 1407-1417). The Swiss Cancer Group adopted this
      regimen for a confirmatory phase III trial but used the same dose-intensity of
      fluorouracil in both treatment arms. PATIENTS AND METHODS: Patients with
      inoperable or metastatic colorectal cancer were randomized to receive monthly FU
      400 mg/m2/day plus LV 20 mg/m2/day as intravenous push daily for five days, or FU
      alone. RESULTS: Three hundred nine of the 310 patients randomized were eligible
      and included in the analysis. The objective response rate for patients with
      measurable disease was 9% with FU alone and 22% with FU-plus-LV (P = 0.0001). The
      median progression-free survival was 3.9 versus 6.2 months (P = 0.003) and the
      overall survival 10 versus 12.4 months (P = 0.02). The major prognostic factors
      for survival were performance status, weight loss, and disease symptoms. WHO > 2
      toxicity, consisting of stomatitis (P = 0.001), diarrhea (P = 0.001), and nausea
      (P = 0.001), was more pronounced for FU-plus-LV, without fatal events.
      CONCLUSIONS: This is the largest published randomized trial to compare FU-plus-LV
      to FU alone in advanced colorectal cancer. It confirms the survival benefit
      obtained from biomodulating monthly FU with low-dose LV. The toxic effects of FU
      plus-LV were acceptable to most patients, and they responded well to FU dose
      reductions. In the absence of an ideal dose-intense FU monotherapy regimen,
      monthly FU with low-dose LV provides a simple and economical means by which to
      achieve adequate FU efficacy in the treatment of advanced colorectal cancer.

PMID- 9653496
TI  - Improvement and plateau in survival of small-cell lung cancer since 1975: a
      population-based study.
AB  - BACKGROUND: Cytotoxic therapy appears to have improved short-term survival for
      patients with small-cell lung cancer, but little is known about the results for
      unselected patients and trends in long-term survival. PATIENTS AND METHODS: One
      thousand seven hundred ninety-six patients with small-cell lung cancer diagnosed
      between 1975 and 1994 in southeastern Netherlands. We studied treatment policy
      for and survival of unselected patients since 1975, when cytotoxic therapy
      emerged. RESULTS: The proportion patients receiving chemotherapy, with or without
      irradiation, almost tripled from 30% to 82% for patients younger than 70 years of
      age and from 15% to 56% for those over 70, whereas the proportion receiving only
      radiotherapy decreased from 36% to 5% in both age groups. The short-term (< 2
      year) survival rate improved markedly between 1975 and 1989, especially for
      patients younger than 70 (median survival increased from five to 10 months). Two
      year survival remained poor (8%). Two percent of all patients younger than 70
      years at diagnosis survived for at least eight years, but these patients still
      represent an excess five-year mortality of 39%. CONCLUSIONS: In southeastern
      Netherlands short-term survival of patients with small-cell lung cancer improved
      markedly up to the end of the 1980s, but a major impact on cure rates has not
      been achieved.

PMID- 9653497
TI  - Evaluation of the EORTC QLQ-C30 questionnaire: a comparison with SF-36 Health
      Survey in a cohort of Italian long-survival cancer patients.
AB  - BACKGROUND: Despite the large amount of data available about the EORTC QLQ-C30
      questionnaire, there have been very few studies focussed on long-survival cancer
      patients, and no data are available on its performance in the Italian setting.
      PATIENTS AND METHODS: Within the framework of a project aimed at evaluating the
      characteristics of available HR-QOL questionnaires in the Italian language, the
      EORTC QLQ-C30 questionnaire together with the Short Form 36-item Health Survey
      (SF-36) were mail-administered to a sample of patients previously recruited in
      two large multicenter randomized clinical trials on early breast and colon
      cancers. The properties of the questionnaire were evaluated using standard
      psychometric techniques and correlation analyses with demographic and clinical
      independent variables. RESULTS: In the sample of patients who sent back the
      questionnaires under evaluation, the EORTC QLQ-C30 showed satisfactory
      acceptability (response rate = 64% and very low prevalence of missing at item and
      scale level), and the psychometric analyses confirmed the multi-dimensional
      conceptualisation in terms of convergent and discriminant validity. Moreover,
      EORTC QLQ-C30 scales showed substantial correlation with the homologous SF-36
      scales. Few socio-demographic (age, gender, schooling) and clinical (type of
      cancer disease) variables were associated with HR-QOL. Breast cancer patients
      reported, on average, worse physical health-related scores, but after adjustment
      for age and education, most of the differences disappeared. CONCLUSIONS: These
      findings confirm the validity and robustness of the EORTC QLQ-C30 in this sample
      of long-survival Italian cancer patients. Further ad hoc validation studies are
      required to evaluate its significance in these particular patients.

PMID- 9653498
TI  - Mandibular pain as the leading clinical symptom for metastatic disease: nine
      cases and review of the literature.
AB  - BACKGROUND: Metastases to the jaws are a rare phenomenon. Nevertheless, the
      appearance of non-specific symptoms such as toothache can signal the onset of
      neoplastic disease in some patients. PATIENTS: In this article, we present
      details of a 74-year-old patient with a history of breast cancer to illustrate
      this point. Retrospectively, covering a time span of one year, we could identify
      nine patients (1.2%) with metastatic disease to the mandible out of a total of
      763 patients referred to our Maxillofacial Surgery department with non-specific
      jaw pain. RESULTS: Four patients were subsequently diagnosed as having breast
      cancer, two had lung cancer, one prostate cancer, one renal cell carcinoma and
      one adenocarcinoma of unknown primary site. Only three of these patients had
      documented tumor spread to bones before the onset of jaw pain. In the other
      patients, the dental symptoms were either the first sign of a generalized
      neoplastic disease, or indicated relapse of disease after long term disease free
      interval. However, further work up disclosed generalized tumor spread with
      additional organ- or bone-lesions in all patients, and the median survival was
      only six months (range 3.5(-)+22) from diagnosis. CONCLUSION: Pain of uncertain
      origin in the jaws should alert clinicians to the potential of metastatic disease
      in patients with a history of cancer and a bone scintigraphy should be done to
      rule out metastatic involvement. Although metastatic lesions in this area usually
      herald generalized neoplastic spread according to our experience, prompt
      diagnosis nevertheless can lead to useful palliation and an enhanced quality of
      life.

PMID- 9653499
TI  - Ifosfamide given by continuous-intravenous infusion in association with
      vinorelbine in patients with anthracycline-resistant metastatic breast cancer: a
      phase I-II clinical trial.
AB  - BACKGROUND: Vinorelbine (VNR) is highly active in metastatic breast cancer (MBC)
      and has shown an overall response rate of 40%-50% as first-line treatment. In
      vitro, a synergy has been observed between this drug and ifosfamide (IFX). In
      addition, the pharmacokinetics of IFX suggest that it may have greater activity
      when given by continuous-intravenous infusion (c.i.v.i.). The aim of this study
      was, therefore, to assess the antitumor efficacy and toxicity of the combination
      of bolus VNR and c.i.v.i. IFX as second-line therapy in anthracycline-resistant
      breast cancer patients. PATIENTS AND METHODS: Forty-two patients with MBC who had
      already received anthracycline-based chemotherapy were treated with a regimen
      consisting of IFX, by c.i.v.i. for 72 hours and bolus VNR. The courses were
      repeated every three weeks for a maximum of eight cycles. Four dose
      intensification steps were planned: IFX, 1.5 g/m2 on days 1-3 + VNR, 30 mg/m2 on
      day 1 (six patients); IFX, 2 g/m2 on days 1-3 + VNR, 25 mg/m2 on day 1 (six
      patients); IFX, 1.8 mg/m2 on days 1-3 + VNR, 25 mg/m2 on days 1 and 8 (six
      patients); IFX, 2 g/m2 on days 1-3 + VNR, 25 mg/m2 on days 1 and 8 (24 patients).
      Sodium-2-mercaptoethane sulfonate (mesna) was associated with IFX at an infusion
      ratio of 1:1 and, once the infusion was completed, per os every four hours for
      three times. RESULTS: All of the 42 patients entered were assessable for
      toxicity, and 41 of them for response. Neutropenia was the most frequently
      occurring toxicity, but only five patients at the highest dose level (11.9%)
      presented grade 4, and none of those at the first three steps. Other significant
      toxic effects were mild (only grade I-II). The median relative dose intensity was
      95% at the highest dose level and all of the treatments were administered on an
      out-patient basis. The overall response rate was 36.5% with a CR rate of 4.8%
      (two of 41 patients, all at the highest dose level) and a PR rate of 31.7% (13 of
      41 patients). The median response duration was 7.0 months (range 2-13 months).
      CONCLUSIONS: The present phase I-II study shows that the IFX and VNR combination
      is an active and well-tolerated treatment in MBC and provides an alternative to
      taxanes for patients previously treated with anthracyclines.

PMID- 9653500
TI  - Clinical phase I study with one-hour paclitaxel infusion.
AB  - BACKGROUND: Paclitaxel (PAC) is one of the major anti-cancer drugs, effective in
      different tumors. Studies with 24-hour infusion with 135 mg/m2 and a three-hour
      infusion with 175 mg/m2 showed a significant schedule-dependent toxicity. We
      evaluated a one-hour infusion schedule within a phase I study to determine the
      dose limiting toxicity (DLT), the maximum tolerated dose (MTD), and the anti
      cancer efficacy. PATIENTS AND METHODS: Patients with advanced malignant tumors
      were treated within cohorts by one-hour infusional paclitaxel starting with 150
      mg/m2 and stepwise escalation with 25 mg/m2 increments. Therapy was repeated in
      three-week intervals. Cycles were repeated until progression. Toxicity was
      closely monitored, anti-cancer efficacy was only evaluated in those patients who
      received at minimum two treatment cycles. RESULTS: Thirty-four patients entered
      the study (11 NSCLC, five SCLC, seven ovarian cancer, one cervix cancer, nine
      MBC, one HN cancer). The MTD was PAC 250 mg/m2. The DLT was central and
      peripheral neuropathy (WHO grade 3). Other significant toxicities were fatigue,
      myalgia/arthralgia and paraesthesia. No significant myelotoxicity was observed.
      Totally twentyone patients were evaluable for response. A partial response was
      observed in five (24%) patients (two NSCLC, two ovarian cancer, one head and neck
      cancer). Three (14%) patients had stable disease and in 13 (62%) patients
      progressive disease was observed. CONCLUSIONS: Paclitaxel 225 mg/m2 on day 1
      administered as one-hour infusion and repeated every three weeks can be given
      safely, featured no relevant myelotoxicity, and is the recommended dose for phase
      II studies.

PMID- 9653501
TI  - Paclitaxel hypersensitivity reactions: a role for docetaxel substitution.

PMID- 9653502
TI  - Pneumocystis carinii pneumonia in breast cancer.

PMID- 9653503
TI  - Amerind taxonomy and testable hypotheses.
AB  - The acceptance of a 30,000 yr B.P. age for Valsequillo sets new parameters for
      hypotheses of Paleoindian entry into America. A review of Amerind taxonomy
      defines the early groups as Otamid-Sundadonts. Isolation in America led to an
      adaptive radiation that has implications for the origin and dispersal of
      Pithecanthropus.

PMID- 9653504
TI  - [Secular trend in body height since the Neolithic period].
AB  - The body height of children and adults is estimated on the basis of skeleton
      material from the middle Elbe-Saale region since the Neolithic period. The men's
      body height was calculated according to Breitinger (1938), the women's body
      height according to Bach (1965), and the children's body height according to
      Telkka et al. (1962). These estimates are compared with the mean body height of
      living persons from the adult population and of Jena schoolchildren,
      respectively. These are the following essential results: 1. Since 7000 years ago
      changes of body height can be observed. There was an increase of the mean body
      height from the Neolithic period until the Bronce age. In the A.D. era no clear
      changes of the average values can be found until about the 12th century, after
      which there occurred decreases seen until the 19th century. 2. The greatest
      secular trends in children and adults arise in our century. 3. The influence of
      different environmental factors on the body height in past and present is
      discussed and the sex-specific reactions to changes of these environmental
      factors are described. 4. It is pointed out that social, and/or geographic
      influences can cause changes of the body height calculated from skeleton
      material.

PMID- 9653505
TI  - [Tooth root length and tooth neck diameter as indicators in sex determination of
      human teeth].
AB  - The length of the dental root and the diameter of the tooth neck are odontometric
      parameters which to date have rarely been used for the differentiation of the
      sexes. Teeth of 166 individuals from the early medieval burial ground of
      Eichstetten (south Germany) were available for examination. A correlation
      analysis was performed to show the possible dimensional interrelation of teeth
      which, however, applies only to the dental neck parameters. Using only diameters
      of the tooth neck and length of dental roots, it was possible to perform a new
      sex determination for 68 of the 166 individuals. It shows a good coincidence with
      a traditional sex determination. A traditional sex determination, performed in
      advance, as well as the archeological assignment of typical sex related grave
      goods were used for verification. For future sex determination based on teeth,
      examinations are recommended to be restricted to the six-year molar, the first
      upper premolar and, in particular, the canine. Also the dental neck diameter
      proved to be more useful than the crown diameter. Dental root lengths can be
      neglected. By comparing the results with those of a second Alamannic burial
      ground it could be established that discriminant analyses performed within the
      same population are highly congruent.

PMID- 9653506
TI  - Size correlation in Wormian bones.
AB  - This study examines the correlation in size between some Wormian bones (lambda
      bone and lambdoid ossicles) and between them and some cranial measurements
      concerning the cephalic index and cranial capacity. The sizes of the lambda bone
      and lambda ossicles are not correlated among themselves. The female ossicle sizes
      are correlated with cranial length and width.

PMID- 9653507
TI  - Smoking status and its effect on cardiorespiratory system, body dimension and
      plucking performance of Oraon tea garden labourers.
AB  - Oraon tea leaf pluckers were examined in terms of their cardiorespiratory
      functions which include blood pressure measurements and a number of lung function
      tests. Anthropometric measurements and information on smoking history were
      obtained. It is known from earlier studies that the individuals studied belong to
      more or less similar economic and nutritional background. The results suggest
      that smoking has an effect on cardiorespiratory functions, and may have an
      indirect effect an anthropometric traits, but no effect of smoking on work
      performance could be established from the present study.

PMID- 9653508
TI  - [Arm folding--an overview].
AB  - The literature concerning arm folding is reveiwed. This analysis could be based
      on 121 populations. In addition to this the paper discusses incidence, sex, age
      differences and genetical problems including twinning. The incidence of left arm
      folding ranges from 20% to 65% (mean value 54%). The review shows a predominance
      of the left-type in Europe. Age and sex differences are only small. Between arm
      folding and handedness no relationship could be found, and only a very weak one
      between arm folding and hand clasping. 13 authors examined arm folding in
      families, and 2 in twins. The family data suggest that arm folding may be under a
      certain genetic control, yet it is clear that no simple genetic model concerning
      the inheritance can be assumed. Monozygotic as well as dizygotic twins show a low
      rate of concordance, and the frequencies of R-R, R-L and L-L pairs in monozygotic
      and dizygotic twins show a binomial distribution.

PMID- 9653509
TI  - Thermal and EMG biofeedback learning in nonhuman primates.
AB  - Four monkeys were found able to learn to raise and lower hand temperature and to
      reduce muscle tension to low levels using feedback from the target physiological
      system. The establishment of this model of biofeedback learning in monkeys
      enables work on mechanisms mediating the modes of biofeedback most used in
      clinical practice. Results suggest that biofeedback learning does not need to be
      mediated by the type of human-specific cognitive strategies employed by humans.

PMID- 9653510
TI  - Emotionally triggered asthma: a review of research literature and some hypotheses
      for self-regulation therapies.
AB  - Asthma is a common disease whose morbidity and mortality are rapidly increasing.
      Panic disorder is common in asthma. Panic, other negative emotions, and a passive
      coping orientation may affect asthma by producing hyperventilation, increased
      general autonomic lability, a specific pattern of autonomic arousal that may
      cause bronchoconstriction, and/or detrimental effects on health care behaviors.
      Generalized panic is a risk factor for increased asthma morbidity. A repressive
      coping style also appears to be a risk factor for asthma morbidity because it is
      accompanied by an impaired ability to perceive symptoms, a necessary prerequisite
      for taking appropriate remediation. Several self-regulation strategies are
      hypothesized to be useful adjuncts to asthma treatment. Preliminary research has
      been done on relaxation therapy, EMG biofeedback, biofeedback for improved
      sensitivity in perceiving respiratory sensations, and biofeedback training for
      increasing respiratory sinus arrhythmia. It is hypothesized that finger
      temperature biofeedback also may be a promising treatment method, and that
      relaxation-oriented methods will have their greatest effect among asthmatics who
      experience panic symptoms, while improved perceptual sensitivity will be helpful
      both for patients who panic and those with repressive coping styles.

PMID- 9653511
TI  - Disinhibition in the gamma motoneuron circuitry: a neglected mechanism for
      understanding myofascial pain syndromes?
AB  - Dysregulation in the gamma motoneuron circuitry is proposed as one mechanism to
      explain the development of trigger point activity in myofascial pain syndrome.
      Dysregulation in this context is defined operationally as significantly (and
      functionally) different levels of electrical activity detected in the same muscle
      on the left and right sides of the body that is persistently present with
      movement of that muscle. Neurophysiological concepts as they pertain to muscles
      and motor control principles are reviewed. Research is integrated that ties
      together material from diverse fields of psychology and medicine. Dysregulation
      in the gamma motoneuron circuitry may lead to disinhibition of muscle that causes
      it to remain hyperactive after contraction, generate excessive electrical
      activity during movement, and/or inappropriately coactivate with other muscles
      during movement. Any or all of these phenomena may occur with dysregulation. Such
      dysregulation may be corrected by learning. Immediate clinical implications are
      discussed, including the addition of specifically targeted neuromuscular
      retraining procedures via surface electromyography, as well as some conceptual
      and research issues that require further clarification.

PMID- 9653512
TI  - Potential contributions of neck muscle dysfunctions to initiation and maintenance
      of carpal tunnel syndrome.
AB  - A biomechanical perspective of the carpal tunnel (CT) is reviewed that lends
      itself to an understanding of carpal tunnel syndrome (CTS) from a broader
      pathophysiological perspective than focusing narrowly or solely on nerve
      disturbance in the extremity. A wider integration of physiological systems in the
      etiology and maintenance of CTS is proposed that links muscular dysfunction in
      the neck and possibly elsewhere to dysfunction at the CT. A significant subset of
      individuals who develop CTS have a primary contribution from muscular
      dysfunctions rather distal to the CT itself. Neurophysiological dysregulation of
      normal inhibitory feedback at the level of the motoneuron pool specifically
      involving gamma motoneuron impulses may be a primary contributing mechanism.
      Empirical demonstration of amelioration of CTS symptoms by means of surface
      electromyography (sEMG) retraining of dysfunctional neck muscle patterns is
      reviewed as support for the hypothesized link. The specific retraining techniques
      are described. Future conceptual and research directions are noted.

PMID- 9653513
TI  - Ouabain induces apoptosis on PHA-activated lymphocytes.
AB  - Apoptotic cell death plays a critical role in immune system homeostasis, and c
      myc protooncogene deregulated expression is a component of this programmed
      genomic response. Pharmacological intervention and modulation of peripheral
      lymphocytes apoptosis would have important implications. The present results
      indicate that ouabain, a specific inhibitor of Na+K(+)-ATPase, promotes an
      increased expression of c-myc mRNA, and induces apoptosis in PHA-stimulated
      lymphocytes. Furthermore, this ouabain-induced apoptosis cannot be counteracted
      by the addition of exogenous IL-2.

PMID- 9653514
TI  - Folate transport by prawn hepatopancreas brush-border membrane vesicles.
AB  - The transport system of folic acid (Pte-Glu) by brush-border membrane vesicles
      (BBMV) isolated from prawn (Penaeus japonicus) hepatopancreas, was studied by
      measuring the uptake of Pte-Glu. This uptake was found to have two components,
      intravesicular transport and membrane binding. Membrane binding was not affected
      by the presence of a transmembrane pH-gradient at a short incubation period.
      However, a transmembrane pH-gradient increased membrane binding at 60 min. The
      transport of Pte-Glu appeared to be carrier-mediated, was stimulated by an
      inwardly proton gradient (pH 5.5 outside, 7.4 inside) and was unaffected by a
      sodium-gradient. The relationship between pH gradient-driven Pte-Glu uptake and
      medium Pte-Glu concentration followed saturating Michaelis-Menten kinetics. Eadie
      Hofstee representation of the pH gradient-driven Pte-Glu uptake indicated a
      single transport system with a Km of 0.37 microM and Vmax of 1.06 pmol/mg
      protein/15 s. These findings indicate that BBMV isolated from prawn
      hepatopancreas possesses a Pte-Glu transport system similar to that described in
      mammalian intestine.

PMID- 9653515
TI  - The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester potentiates
      insulin secretion stimulated by glucose and L-arginine independently of its
      action on ATP-sensitive K+ channels.
AB  - The nature of the action of the nitric oxide synthase (NOS) inhibitor NG-nitro-L
      arginine methyl ester (L-NAME) on hormone release from isolated islets was
      investigated. We found that glucose-induced insulin release was potentiated by L
      NAME in the absence or presence of diazoxide, a potent K+ATP channel opener, as
      well as in the presence of diazoxide plus a depolarizing concentration of K+. At
      a low, physiological glucose concentration L-NAME did not influence insulin
      secretion induced by K+ but inhibited glucagon secretion. L-arginine-induced
      insulin release was potentiated by L-NAME. This potentiation was observed also in
      the presence of K+ plus diazoxide. Further, glucagon release induced by L
      arginine as well as by L-arginine plus K+ and diazoxide was suppressed by L-NAME.
      The results strongly suggest that the L-NAME-induced potentiation of insulin
      secretion in response to glucose or L-arginine as well as the inhibitory effects
      on glucagon secretion are largely mediated by L-NAME directly suppressing islet
      NOS activity. Hence NO apparently affects insulin and glucagon secretion
      independently of membrane depolarization events.

PMID- 9653516
TI  - Differential rhodopsin regeneration in photoreceptor membranes is correlated with
      variations in membrane properties.
AB  - Rhodopsin, the major transmembrane protein in both the plasma membrane and the
      disk membranes of photoreceptor rod outer segments (ROS) forms the apo-protein
      opsin upon the absorption of light. In vivo the regeneration of rhodopsin is
      necessary for subsequent receptor activation and for adaptation, in vitro this
      regeneration can be followed after the addition of 11-cis retinal. In this study
      we investigated the ability of bleached rhodopsin to regenerate in the
      compositionally different membrane environments found in photoreceptor rod cells.
      When 11-cis retinal was added to bleached ROS plasma membrane preparations,
      rhodopsin did not regenerate within the same time course or to the same extent as
      bleached rhodopsin in disk membranes. Over 80% of the rhodopsin in newly formed
      disks regenerated within 90 minutes while only 40% regenerated in older disks.
      Since disk membrane cholesterol content increases as disks are displaced from the
      base to the apical tip of the outer segment, we looked at the affect of membrane
      cholesterol content on the regeneration process. Enrichment or depletion of disk
      membrane cholesterol did not alter the % rhodopsin that regenerated. Bulk
      membrane properties measured with a sterol analog, cholestatrienol and a fatty
      acid analog, cis parinaric acid, showed a more ordered, less "fluid", lipid
      environment within plasma membrane relative to the disks. Collectively these
      results show that the same membrane receptor, rhodopsin, functions differently as
      monitored by regeneration in the different lipid environments within
      photoreceptor rod cells. These differences may be due to the bulk properties of
      the various membranes.

PMID- 9653517
TI  - Computational observation of an ion permeation through a channel protein.
AB  - The ion permeation process, driven by a membrane potential through an outer
      membrane protein, OmpF porin of Escherichia coli, was simulated by molecular
      dynamics. A Na+ ion, initially placed in the solvent region at the outer side of
      the porin channel, moved along the electric field passing through the porin
      channel in a 1.3 nsec simulation; the permeation rate was consistent with the
      experimentally estimated channel activity (10(8)-10(9)/sec). It this simulation,
      it was indicated that the ion permeation through the porin channel proceeds by a
      "push-out" mechanism, and that Asp113 is an important residue for the channel
      activity.

PMID- 9653518
TI  - Depression, cognition, and functional correlates of recovery outcome after
      traumatic brain injury.
AB  - The present study investigated the prevalence and magnitude of depressive
      symptomatology in a sample of patients who had sustained traumatic brain injury
      (TBI) six months earlier. Depression was examined as a function of recovery
      outcome status, and its association with neuropsychological functioning, personal
      competency, and employability was also explored. Subjects were 100 patients who
      had previously sustained moderate-to-severe TBI who were enrolled as research
      subjects in the UCLA Brain Injury Research Center, and 30 matched control
      subjects who had sustained traumatic injuries other than to the head six months
      prior to evaluation. The results showed a significant association between
      depression and recovery status as measured by the Glasgow Outcome Scale (GOS). A
      significant majority of depressed subjects were found in the poorer GOS outcome
      groups (severe and moderate disability), compared to TBI subjects who had good
      GOS outcomes, and control subjects. This association was also reflected in the
      magnitude of the mean depression scores on two self-report measures of
      depression. However, no association was found between depression status and
      performance on the neuropsychological measures. Effects of depression were found
      only on an examiner-rated Patient Competency scale, and a metacognition measure
      based on self-report. These results are discussed in terms of brain injury
      severity, recovery status, and metacognition issues in TBI and other disorders.

PMID- 9653519
TI  - Neuropsychological, psychosocial and vocational correlates of the Glasgow Outcome
      Scale at 6 months post-injury: a study of moderate to severe traumatic brain
      injury patients.
AB  - Traumatic brain injury (TBI) subjects at Glasgow Outcome Scale levels 3 (severe
      disability), 4 (moderate disability), 5 (good recovery), and an other-injury
      control group (OIC) were compared in terms of neuropsychological, psychosocial,
      and vocational functioning 6 months after injury. Subjects were a sample of 100
      patients with a moderate to severe traumatic brain injury (TBI) and a matched
      sample of 30 other-injury control subjects (OIC) enrolled in the UCLA Brain
      Injury Research Center study of TBI outcome. Overall, the results showed a
      systematic decrease in mean neuropsychological test performance as a function of
      increasing GOS severity, as well as an increased prevalence of symptoms of
      depression and lower ratings on measures assessing employability and capacity for
      self care. TBI patients in the 'severe' and 'moderate disability' groups were
      distinctly inferior to the 'good recovery' and 'OIC' groups, who were quite
      similar to each other in terms of cognitive, psychosocial, and vocational
      outcomes. The results demonstrate overall support for the predictive and
      concurrent validity of the GOS 6 months post injury. Despite these results, which
      strengthen the utility and appeal of the GOS for multicentre studies, concerns
      still remain regarding GOS category 4 (moderate disability), which was shown to
      lack sufficient discriminability in this study.

PMID- 9653520
TI  - The effects of normal ageing on neuropsychological functioning following
      traumatic brain injury.
AB  - Increasing age is associated with greater absolute neuropsychological impairment
      (e.g. slower processing speed, diminished memory), although it is unclear if
      older individuals with traumatic brain injury (TBI) show greater relative
      impairment than younger individuals with TBI. The current study evaluated the
      effects of normal ageing on TBI by using age-based normative data to calculate
      indices of relative decline from pre-morbid levels (expressed as z-deficit
      scores) for different age groups (20-39 years, 40-59 years, 60+ years). The
      sample included 279 individuals with TBI between the ages of 20 and 65 who were
      assessed in a department of rehabilitation neuropsychology laboratory over a 4
      year period. Spearman correlations and ANOVAs did not show age-related
      differences in relative memory, attention or speed of processing abilities,
      although results did indicate that increasing age is associated with relatively
      less impairment in intelligence. The results suggest that the greater
      neuropsychological impairment noted in older individuals with TBI is most likely
      related to normal ageing. The importance of considering both absolute and
      relative degrees of impairment is discussed.

PMID- 9653521
TI  - Functional assessment of mild traumatic brain injury using SPECT and
      neuropsychological testing.
AB  - The aim of this study was to ascertain whether SPECT and neuropsychological
      testing provide converging evidence of normal and abnormal regional cerebral
      function in patients with mild traumatic brain injury (mTBI). Four patients with
      mTBI were evaluated with SPECT and selected neuropsychological tests with
      putative localizing capabilities to specific cortical regions. The performance of
      each patient on each test was graded as either normal or abnormal. Additionally,
      SPECT images were graded for normal and/or abnormal patterns of regional cerebral
      blood flow (rCBF) in eight regions of the cortex. These data were then used to
      predict outcomes from one modality to the other, i.e. rCBF patterns on SPECT were
      used to predict either normal or abnormal performance on specific tests and
      performance on specific tests was used to predict the presence or absence of rCBF
      abnormalities on SPECT. Statistical analysis of composite data from all four
      patients showed that test performance predicted SPECT findings, but SPECT
      findings did not predict test performance.

PMID- 9653522
TI  - The pathogenesis and clinical significance of traumatic subdural hygroma.
AB  - Subdural hygroma (SDG) is a common post-traumatic lesion. Despite its common
      occurrence, the pathogenesis and clinical significance are uncertain. The author
      reviewed the literature to clarify the present knowledge on the pathogenic,
      diagnostic and therapeutic aspects of this controversial lesion. A trivial trauma
      can cause a separation of the dura-arachnoid interface, which is the basic
      requirement for the development of a SDG. If the brain shrinks due to brain
      atrophy, excessive dehydration or decreased intracranial pressure, fluid
      collection may develop by a passive effusion. Most SDGs resolve when the brain is
      well expanded. However, a few SDGs become chronic subdural haematomas, when the
      necessary conditions persist over several weeks. Since the majority of patients
      with a SDG do not show a mass effect, surgery is rarely required. Outcome is
      closely related to the primary head injury not to the SDG itself. The complexity
      of SDG depends on various factors including the dynamics of absorption and
      expansion, duration of observation, and indication and rate of surgery, besides
      variety of the primary head injury in types and severity. SDG is a common
      epiphenomenon of head injury.

PMID- 9653523
TI  - Transient global amnesia triggered by mild head injury.
AB  - An episode of transient global memory loss was observed in a 27-year-old woman
      following a mild head injury in a car accident. Her clinical and
      neuropsychological profiles were indistinguishable from those of transient global
      amnesia (TGA). This paper argues that a cause-effect relationship may be
      postulated between head trauma and transient memory loss, perhaps as the result
      of a very stressful situation such as a car crash.

PMID- 9653524
TI  - Obsessional disorders during recovery from severe head injury: report of four
      cases.
AB  - Four cases of transient obsessional disorders following severe head injury are
      described within the context of recovery from acute traumatic brain injury (TBI).
      Obsessional features following TBI have important treatment implications in brain
      injury rehabilitation settings, since emergence of this disorder in the acutely
      brain injured patient poses a significant obstacle to interdisciplinary
      rehabilitation. Although the numbers of patients described here and in previous
      reports are too small to draw conclusions about the incidence of obsessional
      disorders following TBI, these cases illustrate the importance of correctly
      identifying and treating obsessional symptoms in the brain injured patient.

PMID- 9653525
TI  - Amantadine: a potential treatment for the minimally conscious state.
AB  - Pharmacologic strategies have been advocated to enhance the neurorehabilitation
      of persons with severe traumatic brain injury. Dopaminergic pathways have been
      felt to play a significant role in arousal. Employing single case design
      methodology we present the case of a survivor of severe traumatic brain injury
      who appeared to have a dose dependent response to the pro-dopaminergic medication
      amantadine. Further research is necessary to clarify the role of pharmacotherapy
      in the improvement of functional outcome.

PMID- 9653526
TI  - Pharmacologic management of movement disorder after midbrain haemorrhage.
AB  - Movement disorders following midbrain haemorrhage are infrequently encountered in
      rehabilitation, and are uncommonly corrected by pharmacologic means. This report
      describes a 20 year-old male with a prior history of cocaine abuse who presented
      with a 4 day history of dysarthria and blurred vision following methamphetamine
      abuse. Physical examination demonstrated hypertension, left facial hemispasm,
      bilateral upward gaze paresis and ataxic gait. Magnetic resonance
      imaging/magnetic resonance angiography (MRI/MRA) showed multifocal parenchymal
      haematomas in the mesencephalic tegmentum, subcortical left front region and
      right anterior thalamus consistent with cavernous angiomas. The patient was
      transferred to rehabilitation on hospital day 5. The following day, he developed
      choreoathetoid movements, dystonia, and aphasia, secondary to an extension of the
      midbrain haemorrhage. Cogentin was initiated with slight improvement in
      choreoathetoid movements. The patient began intensive multidisciplinary
      rehabilitation therapy but after 18 days of therapy, the patient remained totally
      dependent in activities of daily living (ADLs), transfers, mobility and was
      unable to communicate in any manner. A trial of Sinemet was initiated, with
      resultant steady improvement in functional ability over the next month. By
      discharge, the patient was independent in ADLs and ambulation. By 9 months post
      discharge follow-up, the patient was fully independent with normal cognition, and
      had self tapered all medications without ill effect. Dopamine agonist trials of
      appropriate duration appear indicated in cases of movement disorder (paucity or
      excess) following midbrain lesions.

PMID- 9653527
TI  - Forensic psychiatry.

PMID- 9653528
TI  - Sexual recidivism in sex offenders.
AB  - OBJECTIVE: To examine the recidivism rates of the various types of adult sex
      offenders including incest offenders, extrafamilial child molesters,
      exhibitionists, and rapists. METHOD: An examination of the literature over the
      past 4 decades and the data from our own study group. RESULTS: Methodological
      shortfalls and differences across the studies make statistical appraisal of the
      results difficult. Nevertheless, there is a consensus that incest offenders are
      less likely to reoffend compared with extrafamilial child molesters. Rapists and
      exhibitionists are thought to be at a higher risk for recidivism. CONCLUSION: A
      combined actuarial predictive approach in conjunction with empirically guided
      clinical assessment is probably the best method to predict recidivism of sex
      offenders.

PMID- 9653529
TI  - The use of clozapine in the treatment of aggressive schizophrenia.
AB  - The atypical antipsychotic drug clozapine was introduced to clinical practice in
      1972. It is a dibenzodiazepine derivative with, among other known receptor site
      activities, a relatively high D1/D2 receptor affinity ratio. The serious side
      effects of bone marrow suppression and agranulocytosis delayed the acceptance of
      clozapine into common clinical practice but scrupulous application of a
      monitoring protocol led to adequate protection from these side effects. There is
      now a broad consensus about the benefits of clozapine which supports the use of
      clozapine as a first-line treatment of schizophrenia. There is good evidence that
      relapse and rehospitalization drop to 22% of the incidence in preclozapine
      treatment patients. The majority of responders are identified within 4 months of
      treatment. Clozapine has been demonstrated to be an effective treatment for
      neuroleptic refractory patients. Forty percent of clozapine-treated patients show
      significant improvement, with 11% of treated patients showing no residual
      psychosis. This review also describes the results of clozapine on aggressive and
      violent assault in a patient population characterized by severe functional
      deficits, typically chronic schizophrenia with severe impairment, chronic brain
      syndromes, and developmental handicap. Prior to the introduction of clozapine
      therapy, in a chronically disrupted milieu that precluded adequate psychosocial
      programming, seriously assaultive behaviour resulting in peer and staff injury
      was a common occurrence. Evidence suggests that clozapine is an effective medical
      treatment for the target symptoms of hostile agitation, threatening, and
      assaultive violence.

PMID- 9653530
TI  - Stalking. Part I: An overview of the problem.
AB  - OBJECTIVE: This paper is the first of a 2-part review on the topic of stalking.
      It outlines the behaviours involved, epidemiology, motivation of offenders, and
      mental health consequences for the victim. METHOD: Computerized literature
      searches were used to identify relevant papers from psychiatric and legal
      journals. Publications by victims' and women's organizations provided additional
      information. RESULTS: Up to 1 in 20 women will be stalked during her lifetime.
      The majority of victims are female, while the offenders are usually male.
      Stalking behaviours range from surveillance to threatening aggressive or violent
      acts. The majority of stalking relates to failed intimate relationships. Stalkers
      may also suffer from erotomania or obsessional love with a primary psychiatric
      diagnosis. Victims may experience anxiety, depression, guilt, helplessness, and
      symptoms of posttraumatic stress disorder (PTSD). CONCLUSION: Stalking is a
      serious offence perpetrated by disturbed offenders. It can cause major mental
      health consequences, which are often poorly understood by society.

PMID- 9653531
TI  - Stalking. Part II: Victims' problems with the legal system and therapeutic
      considerations.
AB  - OBJECTIVE: This paper is the second of 2 parts reviewing the topic of stalking.
      It focuses on victims difficulties with the legal system and the
      psychotherapeutic tasks for victims and therapists. METHOD: Computerized
      literature searches were used to identify relevant papers from psychiatric and
      legal journals. Publications by victims' and women's organizations provided
      additional information. RESULTS: Victims suffer emotional consequences from being
      stalked. Additional stress is caused by the legal system's lack of understanding
      of the causes and consequences of stalking and inadequate and unenforced laws.
      The treatment of victims requires a comprehensive approach, including education,
      supportive psychotherapy, and discussion of practical measures. Therapists may
      overidentify with the patient's powerlessness or hesitate to take on a case out
      of fear of the stalker. Female therapists may protect themselves against the
      realization of their own vulnerability by blaming the victim, while male
      therapists may feel defensive or overprotective. CONCLUSION: Stalking is a crime
      with major mental health consequences which is often poorly understood by
      society. Therapists need to be aware of the victim's emotional reactions, the
      types of legal and practical supports available, and the possible biases of
      society. Further education and research should be encouraged.

PMID- 9653532
TI  - [Instruments to evaluate fitness to stand trial:a review of recent literature].
AB  - OBJECTIVES: To present current methods used to assess fitness to stand trial
      (FST), draw a parallel between these methods and studies of factors associated
      with decisions regarding FST, and describe the limits inherent to the field of
      FST. METHOD: Survey of the relevant literature from Psychinfo and Medline
      databases from 1967 to 1996 inclusively. RESULTS: Ten instruments were identified
      for the systematic collection of information from persons assessed for FST. The
      description and analysis of their psychometric qualities, however, indicate that
      these instruments present some problems. CONCLUSION: Although some research has
      shown that diagnosis is the factor most associated with decisions regarding FST,
      no instrument includes a systematic assessment of psychopathology. If we take
      into account the possible consequences of these decisions for the accused as well
      as for society, these assessments and the recommendations that follow prove to be
      extremely important.

PMID- 9653533
TI  - Fitness, responsibility, and judicially ordered assessments.
AB  - OBJECTIVE: To compare the characteristics of individuals assessed for fitness to
      stand trial (FST) with those assessed for criminal responsibility (CR). METHOD:
      This study examines all the consecutive requests of FST or CR addressed to the
      only forensic psychiatric hospital in the province of Quebec and 2 prisons in the
      Montreal area over a 1-year period. RESULTS: In all, 170 FST, 52 CR, and 29 both
      FST and CR assessment requests were received (251 subjects). Psychiatrists'
      recommendations and court verdicts of unfitness to stand trial or not criminally
      responsible on account of mental disorders were mostly related to the presence of
      a psychotic-spectrum disorder. There is generally a good agreement between
      psychiatric recommendations and verdicts of the court, with the exception of
      unfitness recommendations. CONCLUSIONS: Defendants referred for a FST or a CR
      assessment displayed similar characteristics. However, although subjects with
      psychotic disorders represented more than one-half of the unfit or not criminally
      responsible verdicts, most of the subjects with psychoses were found competent to
      stand trial or responsible.

PMID- 9653534
TI  - Factors in delays in discharge from acute-care psychiatry.
AB  - OBJECTIVE: To determine if there are any potential opportunities for patients to
      be discharged earlier and to determine what factors are responsible for delays in
      discharge. METHOD: A survey was completed by clinical staff of all patients on
      the wards of 12 adult psychiatry units in the Greater Vancouver Regional Hospital
      District (GVRD) for a 1-day period. The survey included a modified Brief
      Psychiatric Rating Scale (BPRS) and the Discharge Readiness Inventory (DRI). A 1
      month follow-up measured discharge and nondischarge outcomes. RESULTS: Of the 327
      patients surveyed, 42% were ready for discharge at the time of the assessment,
      and 37% of those who were ready were not discharged within 2 weeks. Delayed
      patients had significantly higher scores for disorientation, hallucinations,
      conceptual disorganization, and manifest psychopathology and significantly lower
      scores for Community Adjustment Potential (CAP) (P < 0.05). The most frequent
      reasons given for delays were ongoing medication adjustment, behaviour
      stabilization, and discharge planning. Patients who were delayed were more likely
      to need services, to need or be waitlisted for a residential placement, to be a
      client of the community-based mental health team that provides ongoing support to
      clients living in the community, to have a diagnosis of schizophrenia, and to
      have had no previous psychiatric hospital admission. CONCLUSION: The removal of
      all barriers to delays would reduce lengths of stay by 11% for this sample of
      patients. This would require a shift of about 42 out of 327 beds to an alternate
      level of care. These "earlier discharge patients" will need ongoing medication
      and behaviour monitoring through a variety of community services.

PMID- 9653535
TI  - Alcohol consumption and major depression in the Canadian population.
AB  - OBJECTIVE: Various clinical studies have documented associations between alcohol
      consumption and depressive disorders. In some circumstances, alcohol ingestion
      may cause or worsen depression, whereas in other circumstances the direction of
      causal effect may be reversed. The objective of this study was to evaluate
      associations between alcohol consumption and major depression in the Canadian
      population. METHOD: Data from the Canadian National Population Health Survey
      (NPHS) were analyzed. This survey, conducted by Statistics Canada in 1994, used a
      probability sample of 17,626 subjects. The NPHS included measures of alcohol
      ingestion and a diagnostic screen for major depression (Composite International
      Diagnostic Interview [CIDI] Short Form). RESULTS: Subjects reporting any drinking
      in the year preceding the interview were more likely to have experienced an
      episode of major depression during that time than subjects reporting no drinking.
      Subjects reporting maximal ingestions of 5 or more drinks (and especially 10 or
      more drinks) on at least 1 occasion during the preceding year were also at
      greater risk of major depression than nondrinking subjects or subjects reporting
      smaller maximal ingestions. Neither the average amount consumed daily nor the
      frequency of drinking was associated with major depression. CONCLUSIONS: In the
      general population, there is no simple relationship between the quantity or
      frequency of alcohol consumption and the prevalence of major depression. Any
      drinking and maximal consumption on 1 occasion, however, are related to the
      prevalence of major depression. Further research is needed to delineate causal
      mechanisms so that clinical and public-health interventions can be formulated.

PMID- 9653536
TI  - Binge/purge symptoms and comorbidity in adolescents with eating disorders.
AB  - OBJECTIVE: To identify the diagnostic subtypes of eating disorders (EDs), the
      psychiatric comorbid diagnoses, and associated specific and nonspecific
      psychopathology in a series of 120 adolescents undergoing standardized assessment
      for an ED. METHOD: Consecutive patients referred to our large pediatric hospital
      for ED assessment completed a semistructured diagnostic interview for children
      and adolescents. The following self-report scales were administered to assess
      specific and nonspecific psychopathology: the Children's Depression Inventory
      (CDI), the Brief Symptom Inventory (BSI), the Eating Disorder Inventory 2 (EDI
      2), and the Family Assessment Measure (FAM-III) of family functioning. RESULTS:
      Female subjects with a mean age of 14.5 years and a mean body mass index (BMI) of
      18.1 comprised 93% of the sample. The restrictive subtypes of anorexia nervosa
      (AN) (43%) and eating disorder not otherwise specified (EDNOS) (16%) were the
      most common diagnoses. Patients with restricting symptoms (R) could be grouped
      together because they were more similar to each other with respect to self-report
      symptoms of psychopathology than they were to patients with binge/purge (B/P)
      symptoms and vice versa. Patients with R endorsed significantly fewer subjective
      symptoms, both ED-specific and nonspecific, and rated their families functioning
      better than did B/P patients. Comorbid, current major depressive disorders and
      dysthymic disorders occurred in 66% of subjects, but depressive, dysthymic, and
      oppositional disorders occurred in 96% of those with B/P symptoms. Severity of
      the CDI was the best single discriminator between R and B/P subjects.
      CONCLUSIONS: Adolescents with EDs in the early stage of their illness are similar
      to adults with EDs in the following ways: they meet the Diagnostic and
      Statistical Manual of Mental Disorders (DSM-IV) criteria for subtypes of EDs
      (excluding amenorrhea) and commonly have comorbid psychiatric disorders,
      especially depressive disorders. Patients with B/P symptoms can be distinguished
      from restricting subjects because they endorse significantly more ED-specific and
      nonspecific psychopathology and have a higher frequency of comorbid Axis I
      diagnoses (especially depressive disorders) than restricting patients.
      Oppositional defiant disorder (ODD) occurs more commonly in adolescents with EDs
      associated with B/P symptoms.

PMID- 9653537
TI  - A community-based clinic survey of antidepressant use in persons with
      schizophrenia.
AB  - OBJECTIVE: To determine the rates of antidepressant and antipsychotic use in the
      treatment of schizophrenia. METHOD: The primary therapists at 8 community mental
      health centres in a metropolitan Canadian city completed a survey questionnaire
      for all of their active clients. Information was collected about diagnoses,
      medication treatments, and clinical variables. RESULTS: There were 3555 clients,
      1552 (43.7%) of which had a diagnosis of schizophrenia. Of clients with
      schizophrenia, 94% were prescribed antipsychotic medications, and 11.6% of these
      were also prescribed antidepressant medications. There were differences between
      the combination-treatment group and the antipsychotic-alone group in gender
      ratio, rates of concurrent diagnoses of mood disorder, level of current
      functioning, and total number of hospitalizations. CONCLUSION: In this community
      based sample of clients with schizophrenia, antidepressants and antipsychotics
      are commonly prescribed in combination, even though the rate of concurrent mood
      disorders diagnoses is low. Further studies should clarify the efficacy and
      indications for antidepressant use in this population.

PMID- 9653538
TI  - Re: Boundary violations and personality traits among psychiatrists.

PMID- 9653539
TI  - Re: Severe anticholinergic side effects with venlafaxine-fluoxetine combination.

PMID- 9653540
TI  - Selective serotonin reuptake inhibitor discontinuation syndrome: putative
      mechanisms and prevention strategies.

PMID- 9653541
TI  - Re: A cross-sectional study of private psychiatric practices under a single-payer
      health care system.

PMID- 9653542
TI  - Mirtazapine withdrawal symptoms.

PMID- 9653543
TI  - Family history of DSM-III-R schizophreniform disorder with good prognostic
      features.

PMID- 9653544
TI  - Bioinorganic chemistry and drug design: here comes zinc again.
AB  - The structures and reactions of metal ions in proteins are of tremendous interest
      in bioinorganic chemistry, as is the potential for metals in creating novel
      medicines. New results combine these aspects in describing an unexpected mode for
      metal-mediated drug efficacy that relies on well-established principles of
      metalloprotein structure.

PMID- 9653545
TI  - Small-molecule-based strategies for controlling gene expression.
AB  - A central goal in chemical biology is to gain control over biological pathways
      using small molecules, and the mRNA-synthesizing machinery is a particular
      important target. New advances in our understanding of transcriptional regulation
      suggests strategies to manipulate these pathways using small molecules.

PMID- 9653546
TI  - High-throughput worms. NemaPharm, Inc.

PMID- 9653547
TI  - Protein structures.

PMID- 9653548
TI  - A high-affinity subtype-selective agonist ligand for the thyroid hormone
      receptor.
AB  - BACKGROUND: Thyroid hormones regulate many different physiological processes in
      different tissues in vertebrates. Most of the actions of thyroid hormones are
      mediated by the thyroid hormone receptor (TR), which is a member of the nuclear
      receptor superfamily of ligand-activated transcription regulators. There are two
      different genes that encode two different TRs, TR alpha and TR beta, and these
      two TRs are often co-expressed at different levels in different tissues. Most
      thyroid hormones do not discriminate between the two TRs and bind both with
      similar affinities. RESULTS: We have designed and synthesized a thyroid hormone
      analog that has high affinity for the TRs and is selective in both binding and
      activation functions for TR beta over TR alpha. The compound, GC-1, was initially
      designed to solve synthetic problems that limit thyroid hormone analog
      preparation, and contains several structural changes with respect to the natural
      hormone 3,5,3'-triiodo-L-thyronine (T3). These changes include replacement of the
      three iodines with methyl and isopropyl groups, replacement of the biaryl ether
      linkage with a methylene linkage, and replacement of the amino-acid sidechain
      with an oxyacetic-acid sidechain. CONCLUSIONS: The results of this study show
      that GC-1 is a member of a new class of thyromimetic compounds that are more
      synthetically accessible than traditional thyromimetics and have potentially
      useful receptor binding and activation properties. The TR beta selectivity of GC
      1 is particularly interesting and suggests that GC-1 might be a useful in vivo
      probe for studying the physiological roles of the different thyroid hormone
      receptor isoforms.

PMID- 9653549
TI  - Substrate binding and sequence preference of the proteasome revealed by active
      site-directed affinity probes.
AB  - BACKGROUND: The proteasome is a multicatalytic protease complex responsible for
      most cytosolic protein breakdown. The complex has several distinct proteolytic
      activities that are defined by the preference of each for the carboxyterminal
      (P1) amino acid residue. Although mutational studies in yeast have begun to
      define substrate specificities of individual catalytically active beta subunits,
      little is known about the principles that govern substrate hydrolysis by the
      proteasome. RESULTS: A series of tripeptide and tetrapeptide vinyl sulfones were
      used to study substrate binding and specificity of the proteasome. Removal of the
      aromatic amino-terminal cap of the potent tripeptide vinyl sulfone proteasome
      inhibitor 4-hydroxy-3-iodo-2-nitrophenyl-leucinyl-leucinyl-leucine vinyl sulfone
      resulted in the complete loss of binding and inhibition. Addition of a fourth
      amino acid (P4) to the tri-leucine core sequence fully restored inhibitory
      potency. 125I-labeled peptide vinyl sulfones were also used to examine inhibitor
      binding and to determine the correlation of subunit modification with inhibition
      of peptidase activity. Changing the amino acid in the P4 position resulted in
      dramatically different profiles of beta-subunit modification. CONCLUSIONS: The P4
      position, distal to the site of hydrolysis, is important in defining substrate
      processing by the proteasome. We observed direct correlations between subunit
      modification and inhibition of distinct proteolytic activities, allowing the
      assignment of activities to individual beta subunits. The ability of
      tetrapeptides, but not tripeptide vinyl sulfones, to act as substrates for the
      proteasome suggests there could be a minimal length requirement for hydrolysis by
      the proteasome. These studies indicate that it is possible to generate inhibitors
      that are largely specific for individual beta subunits of the proteasome by
      modulation of the P4 and carboxy-terminal vinyl sulfone moieties.

PMID- 9653550
TI  - Conversion of SB 203580-insensitive MAP kinase family members to drug-sensitive
      forms by a single amino-acid substitution.
AB  - BACKGROUND: Specific inhibitors of protein kinases have great therapeutic
      potential, but the molecular basis underlying their specificity is only poorly
      understood. We have investigated the drug SB 203580 which belongs to a class of
      pyridinyl imidazoles that inhibits the stress-activated protein (SAP) kinases
      SAPK2a/p38 and SAPK2b/p38 beta 2 but not other mitogen-activated protein kinase
      family members. Like inhibitors of other protein kinases, SB 203580 binds in the
      ATP-binding pocket of SAPK2a/p38. RESULTS: The SAP kinases SAPK1 gamma/JNK1,
      SAPK3 and SAPK4 are not inhibited by SB 203580, because they have methionine in
      the position equivalent to Thr106 in the ATP-binding region of SAPK2a/p38 and
      SAPK2b/p38 beta 2. Using site-directed mutagenesis of five SAP kinases and the
      type I and type II TGF beta receptors, we have established that for a protein
      kinase to be inhibited by SB 203580, the sidechain of this residue must be no
      larger than that of threonine. Sensitivity to inhibition by SB 203580 is greatly
      enhanced when the sidechain is even smaller, as in serine, alanine or glycine.
      Thus, the type I TGF beta receptor, which has serine at the position equivalent
      to Thr106 of SAPK2a/p38 and SAPK2b/p38 beta 2, is inhibited by SB 203580.
      CONCLUSIONS: These findings explain how drugs that target the ATP-binding site
      can inhibit protein kinases specifically, and show that the presence of threonine
      or a smaller amino acid at the position equivalent to Thr106 of SAPK2a/p38 and
      SAPK2b/p38 beta 2 is diagnostic of whether a protein kinase is sensitive to the
      pyridinyl imidazole class of inhibitor.

PMID- 9653551
TI  - 19F NMR in the measurement of binding affinities of chloroeremomycin to model
      bacterial cell-wall surfaces that mimic VanA and VanB resistance.
AB  - BACKGROUND: The emergence of bacteria that are resistant to vancomycin, the drug
      of choice against methicillin-resistant Staphylococcus aureus, has made the study
      of the binding characteristics of glycopeptides to biologically relevant
      depsipeptides important. These depsipeptides, terminating in D-alanyl-D-lactate,
      mimic the cell-wall precursors of resistant bacteria. RESULTS: The use of 19F
      labelled ligands in the study of the therapeutically important vancomycin series
      of antibiotics is demonstrated. The substantial simplification of spectra that
      occurs when such labelled ligands are employed is used in the measurement of
      binding affinities of depsipeptides to chloroeremomycin (CE). Large enhancements
      of binding affinities are found at a model bacterial cell-wall surface
      (constituted from depsipeptides that are anchored into vesicles) relative to
      those measured in free solution. CONCLUSIONS: Surface-enhanced binding,
      previously shown for strongly dimerizing glycopeptide antibiotics to normal -D
      alanyl-D-alanine-terminating cell-wall precursors, is now demonstrated for CE to
      the surface of models of VanA- and VanB-resistant bacteria. The effect of
      depsipeptide chain length is shown to be critically important in producing and
      maximizing this enhancement.

PMID- 9653552
TI  - Inhibiting the dimeric restriction endonuclease EcoRI using interfacial helical
      peptides.
AB  - BACKGROUND: Many enzymes are active only in a dimeric form, including a variety
      of type II restriction endonucleases. Disruption of subunit interactions is
      therefore a potential method for multimeric enzyme inhibition. EcoRI is a
      homodimeric restriction endonuclease, the dimeric interface of which consists of
      a four-helix bundle. We set out to design helical peptides to interact with this
      interface and block dimer formation, thus rendering EcoRI inactive. RESULTS: Here
      we describe two synthetic, helical peptides based on the interfacial region of
      EcoRI. Both peptides inhibit the enzyme, but the peptide derived from the alpha 4
      helix of EcoRI had both a higher helical content and better efficacy than a
      variant peptide, alpha 4(Leu), that has three Ile-->Leu mutations (IC50 values of
      27 microM and 90 microM, and helical contents of 29% and 10%, respectively). Size
      exclusion chromatography confirmed that the alpha 4 peptide disrupted
      dimerization of EcoRI, and circular dichroism indicated that EcoRI remained
      folded upon binding to alpha 4. Inhibition with alpha 4 and alpha 4(Leu) was
      shown to be specific for EcoRI, as the dimeric restriction enzyme PvuII was not
      affected by the peptides. CONCLUSIONS: Interfacial peptide inhibitors of the
      dimeric EcoRI were obtained that both inhibit dimerization and endonuclease
      activity. The peptide sequence with a preference for a helical conformation was a
      more effective inhibitor, presumably because the more preorganized state enhanced
      interactions with the helical interface of EcoRI. The specific nature of this
      endonuclease-peptide interaction was also confirmed. The potential of this
      strategy for inhibiting other enzyme classes is currently being addressed.

PMID- 9653553
TI  - Lipitoids--novel cationic lipids for cellular delivery of plasmid DNA in vitro.
AB  - BACKGROUND: Although synthetic nonviral vectors hold promise for the delivery of
      plasmid DNA, their gene-transfer efficiencies are far from matching those of
      viruses. To systematically investigate the structure-activity relationship of
      cationic lipids, a small library of cationic lipid-peptoid conjugates (lipitoids)
      was synthesized. The compounds were evaluated for their ability to form complexes
      with plasmid DNA and to mediate DNA transfer in vitro. RESULTS: Lipid-peptoid
      conjugates were conveniently prepared in high yield using solid-phase synthesis.
      Several lipitoids condensed plasmid DNA into 100 nm spherical particles and
      protected the DNA and DNase digestion. A subset of lipitoids with a repeated
      (aminoethyl, neutral, neutral) sidechain trimer motif conjugated with dimyristoyl
      phosphatidyl-ethanolamine (DMPE) mediated DNA transfer with high efficiency.
      CONCLUSIONS: Automated solid-phase synthesis of cationic lipids allowed the rapid
      synthesis of a diverse set of transfection reagents. The most active compound
      DMPE-(Nae-Nmpe-Nmpe)3 (Nae, N-aminoethyl glycine; Nmpe, N-p-methoxyphenethyl
      glycine) is more efficient than lipofectin or DMRIE-C (two commercial cationic
      lipid transfection reagents) and is active in the presence and absence of serum.
      The activity in the presence of serum suggests potential for applications in
      vivo.

PMID- 9653554
TI  - [Recommendations for surgical therapy planning and interventions in patients with
      AIDS].
AB  - No other disease has exhibited such a significant influence on the behaviour of
      health care workers (HCW) as the AIDS pandemic. Numerous epidemiological data,
      however, have proven that the overall risk of transmission of the human
      deficiency virus (HIV) during surgical interventions is low; it is 0.3% for all
      types of percutaneous exposures. Nevertheless, there still is a need for wider
      adoption of safer surgical techniques to reduce the chances of HIV transmission
      in the operation theatre, which additionally minimize the risk of transmission of
      other blood-borne pathogens. In the case of occupational exposure to HIV
      contaminated blood or body secretions post-exposure prophylaxis should be
      recommended stratified by the type of exposure and source material.

PMID- 9653555
TI  - [Transmissible spongiform encephalopathies: Creutzfeldt-Jakob disease].
AB  - Different diseases of the transmissible spongiform encephalopathy (TSE) group are
      known to affect humans and various animals. Owing to the bovine spongiform
      encephalopathy (BSE) epidemic and the description of the new variant of
      Creutzfeldt-Jakob disease (nvCJD), which is probably linked to BSE, TSE received
      much attention. The nature of the causative agent is still disputed; none of the
      proposed concepts (prions, viruses) can explain all features. It is clear,
      however, that there is a genetic component in susceptibility to infection and in
      development of disease and that transmission may cross the species barrier. This
      paper gives an overview of the first results and latest developments of basic TSE
      research that has focused on in vivo early diagnosis and the prevention of
      possible (also iatrogenic) transmission.

PMID- 9653556
TI  - [Surgery in hepatitis].
AB  - Viral hepatitis belongs to the most important infectious diseases worldwide. More
      than 300 million chronic HBsAg carriers and chronic HCV carriers exist,
      respectively. High endemic areas of viral hepatitis are Asia, Africa, Latin
      America and the Near, Middle and Far East. Viral hepatitis is also very important
      in health care workers. Today viral hepatitis can be differentiated from type A
      to type E (G) based on immunological and molecular assays. While enterally
      transmitted hepatitis type A and type E only induce acute and rare fulminant
      disease, hepatitis type B, C and D often induce chronic progressive disease
      including liver cirrhosis with typical complications due to the portal
      hypertension and with a high rate of association with the development of primary
      liver cancer (HCC). This review focusses on viral hepatitis-related surgical
      problems, including liver transplantation.

PMID- 9653557
TI  - [Fungal infection].
AB  - Untreated dermatological mycoses are easy to diagnose. Once treatment with
      corticosteroids has been initiated the diagnosis of a mycosis can be difficult.
      In the immunosuppressed patient (AIDS patients) typical dermatological
      manifestations can be lacking. Systemic antimycotic therapy requires precise
      detection of the pathogen concerned. Mistakes still made in surgical practice are
      incision of a tumour in the case of tinea profunda and the extraction of nails
      affected by fungi. In the healthy person yeasts are transient organisms present
      in the mouth and intestinal tract in contrast, the mouth and intestinal tract of
      patients in risk make up a reservoir of candida infection that can affect the
      internal organs. Cryptococcosis and aspergillosis are inhaled mycoses. Factors
      predisposing to mycoses influence the duration and the outcome of the course of
      illness. The most important of these factors in surgical practice is the
      immunosuppression. Systemic mycoses are difficult to recognize. In many cases
      organ mycoses can be diagnosed by CT. Continuous investigations of diagnostic
      cultures and serological tests can contribute to the diagnosis. Only
      cryptococcosis can be ascertained early by specific antigen demonstration in the
      serum. For this reason continuous serological testing for cryptococci is
      essential in AIDS patients.

PMID- 9653558
TI  - [Elective early surgery of acute uncomplicated sigmoid diverticulitis--a
      dangerous error?].

PMID- 9653559
TI  - [Recovery and duration of work disability after laparoscopic and conventional
      appendectomy. A prospective randomized study].
AB  - To evaluate whether laparoscopic appendectomy shortens the convalescence and the
      postoperative period until return to work when compared to conventional
      appendectomy, a prospective randomized trial was performed. The major endpoint of
      the study was the time until return to work; minor endpoints were postoperative
      pain, fatigue, operative time and postoperative morbidity. In all, 54 patients
      with a mean age of 29.5 +/- 10.1 years were randomized to open (n = 28) or
      laparoscopic appendectomy (n = 26). Age, sex, body mass index (BMI), American
      Society of Anesthesiology (ASA) rating, job status as well as histologic degree
      of inflammation of the appendix were comparable in the two groups. Operative time
      was 59.2 +/- 15.8 min for laparoscopic and 59.8 +/- 24.4 min for conventional
      appendectomy (P = 0.9). Some 16 laparoscopic appendectomies (62%) were performed
      by board-certified surgeons, while 23 conventional appendectomies (82%) were
      performed by residents (P = 0.003). Postoperative morbidity was comparable
      between the two groups. After laparoscopic appendectomy, pain was rated
      significantly lower on the first, second and fourth postoperative day when
      compared to the conventional group. There were no difference in postoperative
      fatigue between the groups. Time to return to work was 17.0 +/- 6.2 days in the
      laparoscopic group and 18.2 +/- 6.0 days in the conventional group (p = 0.5).
      Laparoscopic appendectomy has no advantages in terms of convalescence and time to
      return to work when compared to open appendectomy and should therefore be limited
      to selected cases.

PMID- 9653560
TI  - [Hospitals, university clinics and the work schedule law].

PMID- 9653561
TI  - [No access to hospital records to evaluate service misuse].

PMID- 9653562
TI  - [Prevention of thromboembolism in surgical practice].

PMID- 9653563
TI  - [Missed thrombosis diagnosis--flagrant malpractice? Decision of the Oldenburg
      supreme court 25 November 1997--5 U 66/97].

PMID- 9653564
TI  - [Why surgeons are accused of malpractice. The American perspective].

PMID- 9653565
TI  - [Early morphological changes in Crohn disease as further evidence for
      conservative resection indications].
AB  - Clinical studies revealed that the size of the margin of resection and the
      microscopic findings at the edge of the specimen did not influence the rate of
      recurrence. Regarding early lesions of Crohn's disease, the aim of the present
      study was to identify morphological alterations which are able to explain the
      clinical findings and are in accordance with the operative procedure. In the
      present study the resection margins of 29 patients with Crohn's disease were
      investigated using the scanning electron microscope. Seventy-three percent of
      patients with histopathologically unaffected resection margins in the small bowel
      and 71% in the large bowel showed early lesions. These consisted of mucosal
      architectural alterations, epithelial bridge formation and goblet cell
      hyperplasia and hypertrophy. Curative resection is not possible, independent of
      the resection margins. The morphological findings underline the correctness of
      the usual operative procedure, namely limited resections in Crohn's disease.

PMID- 9653566
TI  - [Techniques of laparoscopic preparation and current-induced complications.
      Results of a survey in Germany].
AB  - 138 surgical institutions in Germany retrospectively answered a questionnaire on
      available energy sources, techniques of preparation and complications due to the
      use of electric current in laparoscopic surgery. The median experience in this
      field of surgery was 6 years. For common laparoscopic operations the majority of
      surgeons use electrosurgery; only 8% never do so. Except in appendectomy,
      monopolar cautery is preferred for all operations. Other energy devices are of
      minor importance. The overall number of operations reported was nearly 138,000.
      The rate of complications due to the use of electric current was 0.1%. This
      figure is accounted for in equal part by intra- and postoperative burns. The
      complication rate is at the lower end of the range known from the literature.
      Even though the retrospective nature of this analysis may hide a certain number
      of injuries electric, current plays a minor role for complications in
      laparoscopic surgery.

PMID- 9653567
TI  - [Dependence of surgical trauma in aortic interventions on the approach chosen. A
      prospective study].
AB  - Transabdominal aortic replacement is the most widely accepted approach for aortic
      surgery. Several controlled studies report a more favorable outcome after an
      extraperitoneal incision, yet there are an equal number of papers with
      contradictory results. The aim of our study was to assess operative trauma after
      aortic surgery, depending on whether transperitoneal or extraperitoneal access
      was used. As a parameter for the extent of the surgical trauma the concentration
      of Interleukin 6 and acute phase proteins (CRP) was measured pre-, 6 h and 24 h
      after aortic surgery. One group consisted of 34 patients scheduled for aortic
      surgery for exclusion of an abdominal aortic aneurysm. The second group consisted
      of 26 patients who were operated on for aorto-iliac occlusive disease. Each group
      was subdivided into an equal group of patients operated on either extra- or
      transperitoneally. In the retroperitoneal aneurysm patients, a posterolateral
      access was favored, and in patients with occlusive disease an extraperitoneal
      anterolateral approach was chosen. As a result patients with an extraperitoneal
      incision and aorto-iliac occlusive disease required less postoperative
      respiratory support than those operated on transperitoneally. In this subgroup of
      patients there was a significantly reduced synthesis of Interleukin 6 and CRP.
      When a retroperitoneal posterolateral approach was required in aneurysm patients,
      there was no difference between groups. We conclude from our data that only
      patients with limited infrarenal aortic access can benefit, from the
      retroperitoneal incision in terms of a reduced immunological reaction.

PMID- 9653568
TI  - [Ankle para-articular tibial fracture. Is osteosynthesis with the unreamed
      intramedullary nail adequate?].
AB  - In a prospective study, 53 fractures of the distal fifth of the tibia were
      stabilized by unreamed nailing. Additional involvement of the ankle joint
      occurred in 18 patients. 50 patients returned for follow-up. In 30 patients tibia
      and fibula were fractured at the same (distal) level; in 20 patients the fracture
      of the fibula was located more proximally. In 12 patients the fractures extended
      into the tibial pilon. Severe soft tissue damage was seen in 24 fractures (18
      open, 6 closed). Ninety percent of all fractures healed uneventfully without
      further surgical intervention after unreamed nailing. In two patients the
      unreamed nail had to be exchanged for a reamed tibial nail. Bone grafting and
      secondary dynamization of the nail by removal of a proximal interlocking bolt
      were performed in one case each. Thirty-one fractures healed in anatomical
      position. Valgus or varsus angulation of less than 5 degrees occurred in 18
      patients. One fracture healed with rotatory angulation of 15 degrees. The highest
      rate of complications (22%) was seen in patients with distal fractures of the
      fibula without additional plating (of the fibula). There was no deep infection.
      Tibial fractures close to the ankle joint can be managed by unreamed nailing.
      Distal fractures of the fibula should be stabilized by additional plating.
      Because of the unreamed technique of implantation this procedure can also be used
      in grade II or III open fractures.

PMID- 9653569
TI  - [Invagination of the vermiform appendix in mucinous cystadenoma].
AB  - Intussusception of the appendix vermiformis in adults is an uncommon event. The
      combination of a mucinous cystadenoma with an intussuscepted appendix is
      extremely rare. Clinical symptoms are nonspecific; in most cases the correct
      diagnosis is not made before surgical exploration. With the radiologic and
      endoscopic presentation of a polypoid lesion of the caecum, a neoplasm is often
      considered. Endoscopic appendectomy or disinvagination by enema have been
      described. Thus the definitive therapy is surgery and depends on the histological
      diagnosis.

PMID- 9653570
TI  - [Perforated diverticulum of the vermiform appendix].
AB  - Diverticulitis of the vermiform appendix is an often disregarded disease.
      Diagnosis follows after appendectomy due to inflammatory complications in the
      form of diverticulitis and appendicitis. Diverticula can also be found as a
      reason for complaints in histologically unaltered appendix or as an incidental
      finding. Diverticula of the vermiform appendix are classified as false (acquired)
      or true (congenital). We report on the case of a 57-year-old man with a
      perforated appendix diverticulum as reason for peritonitis and a paralytic ileus
      of the colon and small intestine.

PMID- 9653571
TI  - [Superficial femoral vein as vascular graft in surgical therapy of mycotic
      aneurysm of the common iliac artery].
AB  - A 38-year-old polytoxicomanic male patient developed an occlusion of both
      popliteal arteries associated with an aneurysm of the right common iliac artery.
      A septic cause was suspected and an antimycotic therapy was instituted, but the
      diameter of the aneurysm increased to 3 cm during 6 months. Moreover, multiple
      periarterial abscesses occurred. The aneurysm was resected and the iliacal axis
      reconstructed in situ, using a superficial femoral vein interposition. Six months
      after operation, patency was confirmed by duplex sonography. Phlebodynamic
      examinations showed normal flow functions at the donor site.

PMID- 9653572
TI  - [Patient motivation--an essential therapeutic tool].
AB  - A deciding factor for the future functioning of a hand with a mutilating hand
      injury is the self-motivation that the patient brings with him to rehabilitation.
      This is illustrated in the case of a guitar teacher who returned to his career
      after subtotal and total finger amputation of his left hand (used for gripping
      chords). With consistent exercise on his instrument he compensated for the
      functional deficits of his hand and won a law suit against his employer who
      denied that he had the physical ability to play the classical guitar. It is more
      clear than ever that an injured person is jointly responsible, through self
      motivation in the working process, for more-or-less complete rehabilitation. It
      is not uncommon in a system of job-sharing in which several members of the health
      service (surgeons, physiotherapists, social workers, general practitioners) must
      co-ordinate their work, for the patient--if he does not involve himself--to fall
      by the wayside. It is shown how inherent and rewarding it can be to support the
      patient in his desire to return to work. Apart from that, we hope that this
      example will be an encouragement to those similarly affected.

PMID- 9653573
TI  - [Acute arterial occlusion in an arteriosclerotic vessel].

PMID- 9653574
TI  - [Surgical procedure in stomach ulcer and duodenal ulcer].

PMID- 9653575
TI  - The lack of circadian timing in two intertidal invertebrates and its significance
      in the circatidal/circalunidian debate.
AB  - The control of the timing of gaping in the clam Austrovenus stutchburyi does not
      involve a circadian mechanism. The lack of a circadian timer is shown by the
      uniform pattern in gaping in constant conditions (CC) regardless of the
      relationship between the tidal cycle and the day/night cycle at the time of
      collection; it is also shown by the fact that, in nontidal conditions, a 24 h
      light-dark (LD) cycle fails to entrain persistent rhythmicity. The crab
      Macrophthalmus hirtipes also lacks a circadian oscillator. Both of these
      intertidal dwellers, however, exhibit endogenous tidal rhythmicity. The features
      of the tidal patterns they display in CC can be accounted for using the
      circalunidian (i.e., approximately 24.8 h) model of a tidal timing system but, as
      they lack circadian timers, cannot be explained by the circatidal (i.e.,
      approximately 12.4 h)/circadian model. This demonstrates that, of the two
      hypothetical models of the clock system driving endogenous tidal rhythms, only
      the circalunidian one has universal applicability.

PMID- 9653576
TI  - Circadian rhythm of activity in Japanese quail in constant darkness: variability
      of clarity and possibility of selection.
AB  - In conditions of constant darkness, interindividual variability in the clarity of
      circadian rhythmicity was observed in sexually immature young quail, with birds
      classified as more or less rhythmic or arrhythmic. The relative clarity of this
      circadian rhythm was observed on the actograms by measurement of the
      autocorrelation coefficient ratio over 12 cycles. Autocorrelation coefficients
      were calculated from sequential series of total activity over 12-minute periods.
      Crosses of selected phenotypes with different clarities of rhythmicity were
      conducted in order to study the possibility of selection of this characteristic.
      From a random population (N = 42, twice), pairs of the most rhythmic birds (3
      families), and pairs of arrhythmic birds (4 families) were reared.
      Autocorrelation coefficient ratios of F1 birds from rhythmic families (N = 54)
      were greater than those of F1 birds (N = 48) from arrhythmic families (t-test, p
      < .0001). These ratios in offspring were significantly correlated with that of
      the mean parent of each clutch of siblings (N = 102, r = .35, p = .0003). This
      result was maintained in a second generation (F2) of birds, for which significant
      differences in expressed rhythmicity were observed. That is, autocorrelation
      coefficient ratios of F2 birds from two rhythmic families (N = 30) were greater
      than those of F2 birds from arrhythmic families (N = 20) (t-test, p = .039).
      Comparison of F2 outbred and inbred birds from rhythmic pairs showed greater
      values of autocorrelation coefficient ratios in the case of inbred birds (N = 16)
      than for outbred birds (N = 30; t-test, p = .036). There was no difference
      between outbred (N = 20) and inbred birds (N = 15) from arrhythmic pairs.
      Therefore, selection of a rhythmic strain seems possible, whereas crosses between
      two arrhythmic birds may also give rise to rhythmic birds. Comparisons between
      rhythmic birds of different families did not show differences in the free-running
      period of the circadian rhythm, which is true also for rhythmic birds bred from
      two arrhythmic parents. Therefore, our selection procedure did not seem to be
      based on the characteristics of the pacemaker itself, but rather on a downstream
      event. Although the parents were not selected on the basis of quantity of
      activity per cycle or on the duration of the active phase, significant
      differences among the offspring of different families were shown.

PMID- 9653577
TI  - Aggressive and sexual social stimuli do not phase shift the circadian temperature
      rhythm in rats.
AB  - The objective of the present study was to determine whether the rat circadian
      system is sensitive to social stimuli. Male rats were subjected to a sociosexual
      interaction with an estrous female or to an aggressive interaction with a
      dominant male conspecific. The interactions lasted for 1 h and took place in the
      middle of the circadian resting phase. Control animals were picked up and handled
      for a few minutes, but were otherwise left undisturbed. Animals were housed under
      constant dim red light during the whole period of the experiment. To assess the
      effects of the interactions on free-running circadian rhythmicity, body
      temperature was measured by means of radio telemetry. neither the sociosexual
      interaction with a female nor the aggressive interaction with another male
      induced phase shifts or changes in the free-running period. The rat circadian
      system does not seem to be sensitive to social stimuli directly. Moreover, the
      finding that aggressive interactions do not phase shift circadian rhythms
      indicates that the endogenous pacemaker in rats is not sensitive to stressors.

PMID- 9653578
TI  - Rhythmic patterns in incidence of peptic ulcer perforation over 5.5 decades in
      Norway.
AB  - The incidence of ulcer perforation in 1480 patients treated in the Bergen area of
      Norway between 1935 and 1990 was analyzed for daily (circadian), weekly
      (circaseptan), and yearly (circannual) time effects. A circadian rhythm was found
      overall that was reproducible and fairly stable across seasons, decades, and days
      of the week. After subgrouping, a circadian rhythm was found in younger patients,
      males, and duodenal perforations, while a 12 h (circasemidian) rhythm
      characterized ulcer perforation for women and for gastric ulcers. Duodenal
      perforations showed highest incidence in the afternoon, while gastric
      perforations showed a major peak around noon and a secondary peak near midnight.
      For duodenal ulcer perforation, the circannual pattern was characterized by a 6
      month rhythm, with significantly higher incidence in May-June-July and in
      November-December in most subgroups. A circaseptan rhythm was not found, but
      there was a significantly higher incidence on Thursday-Friday as compared to
      Sunday-Monday. The pathophysiological mechanisms underlying the perforation of an
      ulcer thus seemed to show pronounced circadian and 6-month rhythmic variations,
      much less so circaseptan or circannual rhythms. While it is likely that exogenous
      environmental and/or societal factors play a significant role, variations in
      ulcer perforation may be related to endogenous biological rhythms in
      pathophysiological factors since the circadian pattern of duodenal perforation
      follows that for gastric acidity. Knowledge of the temporal patterns in peptic
      ulcer perforation and associated pathophysiologic factors should prove useful in
      optimizing the chronotherapeutic management of ulcer disease.

PMID- 9653579
TI  - Circadian reactions to nCPAP treatment.
AB  - To determine possible effects of apnea attacks on the spontaneous behavior of the
      circadian system (body temperature, sleeping behavior, vigilance), 11 patients
      with obstructive sleep apnea (OSA) were observed before therapy over a 24 h
      period under a special constant routine (bed-rest study) and again during therapy
      with nCPAP (nasal continuous positive airway pressure). Clinical indicators
      (polysomnographical, subjective sleep quality, etc.) indicated successful
      therapy. During the bed-rest study with nCPAP therapy, the 24 h amplitude of core
      temperature was found to be greater than the amplitude measured before therapy.
      Also, therapy decreased sleep disturbances at night and reduced daytime sleeping
      times. Consequently, the level of subjective vigilance was higher during the
      daytime during therapy. OSA attacks do not only impair sleep; they disturb the
      whole circadian system. This may also impair recuperation and sleep. Further
      research should test whether measurements of the spontaneous circadian system
      could have additional diagnostic value and whether the stabilization of the
      circadian system has therapeutic value.

PMID- 9653580
TI  - Fall and winter hormone concentrations related to stress in pigs identified as
      normal and carrier for stress susceptibility.
AB  - Stress is associated with significant losses in the swine industry. Seasonal
      changes have been shown to affect stress resistance in several species of
      animals. In the present study, we examined the effect of two seasons (fall or
      winter) on plasma insulin, cortisol, and adrenocorticotrophin hormone (ACTH)
      levels from fasted normal and carrier pigs for stress susceptibility when
      submitted to a blood-sampling stressor between 10:00 and 11:00. Comparisons were
      made of 10 diurnally active normal (NN) and 8 carrier (Nn) pigs reared in the
      fall to 9 NN and 10 Nn pigs reared in the winter. The light-dark cycle throughout
      the period of the experiment was 10 h light/14 h dark, with lights on from 07:00
      to 17:00. Feed consisted of the traditional western Canadian swine ration
      consumed ad libitum. Results revealed significant season-by-genotype interactions
      for plasma insulin and ACTH concentrations in response to the blood-sampling
      stressor. The normal pigs displayed a significantly lower plasma insulin level
      during winter compared to the fall season. Plasma ACTH of normal pigs was 18%
      lower in the winter compared to the fall season, although this difference was not
      statistically significant. The carrier genotype, on the other hand, demonstrated
      higher plasma insulin concentration and lower plasma ACTH concentration in the
      winter compared to the fall season. Furthermore, there was a main genotype effect
      in plasma cortisol concentration such that the carrier pigs experienced a greater
      level compared to the normal genotype. Similarly, the carrier pigs had a more
      acute ACTH response to the blood-sampling stressor compared to the normal pigs
      during the fall season. Results have demonstrated that these two seasons of the
      year affect the response of both genotypes to a blood-sampling stressor, with the
      carrier genotype experiencing a more intense stress reaction in the fall season.
      These results further contribute to the recent research indicating that carrier
      pigs for stress susceptibility have a unique stress response.

PMID- 9653581
TI  - Circadian-rhythm-dependent effects of L-NG-nitroarginine methyl ester (L-NAME) on
      morphine-induced analgesia.
AB  - Circadian changes in the interactions between L-NG-nitroarginine methyl ester (L
      NAME), a nitric oxide synthase (NOS) inhibitor, and morphine-induced
      antinociception were investigated by the mouse hot-plate test. Both the basal
      pain sensitivity and morphine-induced analgesia undergo significant 24 h
      variations. L-NAME (40 mg/kg, i.p.) alone did not show any antinociceptive
      activity, but potentiated morphine-induced analgesia when combined with morphine
      at all injection times. In terms of percentage absolute potentiation (%AP), L
      NAME dramatically augmented the analgesic effect of morphine in the late dark
      period at 19 hours after lights on (HALO). It is concluded that nitric oxide (NO)
      is involved in the modulation of the analgesic effect of morphine; thus, the L
      NAME and morphine combination might be beneficial in alleviating pain.

PMID- 9653582
TI  - Flow visualization and 1- and 3-D laser-Doppler-anemometer measurements in models
      of human carotid arteries.
AB  - Pulsatile flow, wall distensibility, non-Newtonian flow characteristics of blood
      in flow separation regions, and high/low blood pressure were studied in elastic
      silicon rubber models having a compliance similar to human vessels and the same
      surface structure as the biological intima models of (1) a healthy carotid artery
      model, (2) a 90% stenosis in the ICA, and (3) 80% stenosis in both the internal
      and external carotid arteries. Flow was visualized for steady flow and pulsatile
      studies to localize flow separation regions and reattachment points. Local
      velocity was measured with a 1-, 2-, or 3-D laser-Doppler-anemometer (LDA). Flow
      in the unstenosed model was Re = 250. In the stenosed models, the Re number
      decreased to Re = 180 and 213 under the same experimental conditions. High
      velocity fluctuations with vortices were found in the stenosed models. The jet
      flow in the stenosis increased up to 4 m/s. With an increasing bifurcation angle,
      the separation regions in the ECA and ICA increased. Increased flow (Re = 350)
      led to an increase in flow separation and high velocity shear gradients. The
      highest shear stresses were nearly 20 times higher than normal. The 90% stenosis
      created high velocity shear gradients and velocity fluctuations. Downstream of
      the stenoses, eddies were found over the whole cross-section. In the healthy
      model a slight flow separation region was observed in the ICA at the branching
      cross-section whereas in the stenosed models, the flow separation regions
      extended far into the ICA. We conclude that a detailed understanding of flow is
      necessary before vascular surgery is performed especially before artificial
      grafts or patches are implanted.

PMID- 9653583
TI  - The non-ionic surfactant Poloxamer 188 (RheothRx) increases plasma and whole
      blood viscosity.
AB  - RheothRx injection is an intravenous formulation of Poloxamer 188, a non-ionic
      block copolymer surfactant which is actually used in clinical studies, e.g.,
      during thrombolysis in acute myocardial infarction. We have analysed the
      influence of RheothRx on plasma and whole blood viscosity of healthy individuals
      in vitro. For that purpose plasma was incubated with 0, 0.75, 3.75 and 18.75
      mg/ml RheothRx and whole blood with a constant hematocrit of 41.4% with 0, 0.4, 2
      and 10 mg/ml RheothRx at 37 degrees C. Viscosity was measured with a Couette
      viscometer at shear rates of 94, 11, 0.9 and 0.1 s-1 as well as with a newly
      developed oscillating viscometer. In contrast to other studies, we found no
      favourable effect of RheothRx on plasma and whole blood viscosity. At the highest
      RheothRx concentration an increase in high and low shear viscosity was observed.
      Erythrocyte morphology remained unchanged. These data, although on normal blood
      in vitro, suggest that the positive effects of RheothRx in vivo may not be caused
      by improved flow properties of blood, but could rely on other mechanisms.

PMID- 9653584
TI  - Quantitative study of fibrinogen molecules' contribution to the inter-red cells
      connections in selected clinical groups of stroke patients.
AB  - In a group of 36 patients with acute ischemic stroke, a study of the influence of
      arterial hypertension on the red cells and fibrinogen interaction was carried out
      by the aspect of fibrinogen molecules' contribution to this phenomenon,
      respecting the role of other plasma biochemical factors. Patients were divided
      into two clinical groups: with and without arterial hypertension. In the blood
      samples with stable haematocrit ratio the following rheological properties were
      estimated: plasma viscosity, yield shear stress (YSS), fibrinogen level and
      parameter R (the difference between two measurements of fibrinogen
      concentration). Also measured were the level of albumin, IgG, IgA, IgM,
      cholesterol, HDL and LDL. The value of parameter R in patients with arterial
      hypertension was lower than in the group without accompanying disease
      (statistical significance was indicated for 80 and 60% of plasma dilution). The
      first group of patients was also characterized by a significant increase of IgA
      level (in comparison with the control group), whereas the red cells and
      fibrinogen interaction measured as a value of YSS was similar in both analysed
      clinical groups. This study indicated a specific character of some
      hemorheological changes in relation to a certain vascular pathology.

PMID- 9653585
TI  - No influence of furosemide on human erythrocyte shape and volume and blood
      viscosity in vitro.
AB  - Furosemide is a diuretic agent which is often given in high concentration
      intravenously. Since erythrocytes have a furosemide-sensitive transport system
      and oral application of furosemide was found to induce an echinocytic shape
      transformation in horses, we have analysed the influence of furosemide on
      erythrocyte shape, volume and blood viscosity in vitro. Increasing plasma
      furosemide concentrations of 0, 1, 10, 100 and 1000 micrograms/ml did not affect
      the erythrocyte volume or shape and left blood viscosity unaffected. We conclude
      that furosemide has no influence on blood rheology in humans.

PMID- 9653586
TI  - Systemic sclerosis: blood rheometry and laser Doppler imaging of digital
      cutaneous microcirculation during local cold exposure.
AB  - A combined study of microcirculation hemodynamics in vivo and blood rheometry has
      been carried out in patients with scleroderma compared to primary Raynaud's
      phenomenon (PRP) and healthy controls (HC). Laser Doppler perfusion imaging was
      used to assess superficial skin blood flow in the fingers before, during and
      after local cold exposure. Blood viscosity was measured at 19 and 37 degrees C.
      Dynamic and transient flows were also investigated. The scleroderma group showed
      a significantly lower level of perfusion before the cold test, that was further
      decreased during and after cold exposure, the difference with PRP being maximal
      during the rewarming period. It also showed a significantly increased viscosity
      (p < 0.05) at low shear rates. Hemorheological behavior of the PRP group was
      similar to the HC group. A significant negative correlation between the LDI
      perfusion and the apparent blood viscosity at low shear rates was found for the
      whole population. These findings suggest that rheological factors may be involved
      in the abnormal cold reactivity of patients with scleroderma.

PMID- 9653587
TI  - Rheological properties of blood as assessed with a newly designed oscillating
      viscometer.
AB  - A newly designed type of oscillating viscometer was tested for blood viscosity
      measurements. The viscometer consists of a probe (either a tube or a rod)
      oscillating at a resonance frequency with amplitudes in the micro- and nanometer
      range. The torsional oscillations are dampened by fluids flowing through the tube
      or surrounding the rod. The degree of damping depends on the viscosity of the
      fluid, which allows to measure viscosity. Data obtained with these instruments
      were compared with those obtained with a conventional Couette viscometer. An
      increase of erythrocyte aggregation by the addition of dextran 70 in vitro led to
      the expected increase of viscosity in the Couette viscometer; in the oscillating
      tube viscometer, however, it remained unchanged, which may be explained by a
      decreased erythrocyte concentration near the tube wall due to increased
      aggregation and flow of erythrocytes in the tube center. In ex vivo experiments
      on blood flowing without anticoagulant directly through the tube viscometer an
      inverse correlation between viscosity and fibrinogen concentration was found.
      This is in contrast to actual knowledge and may indicate that high fibrinogen
      levels have a beneficial rheological effect at the tube or vessel wall. Our data
      suggest that the new oscillating tube viscometer is an interesting tool, which
      may contribute to a more comprehensive understanding of blood flow.

PMID- 9653588
TI  - Red blood cell aging and risk of cardiovascular diseases.
AB  - We hypothesized that due to monthly bloodloss, the mechanical properties of blood
      of premenopausal women are superior to men, and place them at less risk for
      cardiovascular diseases than men in any age group. Rheological properties of
      blood of premenopausal women and age-matched men were compared. It was found that
      male blood possesses an increased viscosity, RBC aggregability and RBC rigidity.
      Additionally, male RBCs were found to have higher mechanical fragility. Since
      women in reproductive age have almost half as many old RBCs and almost twice as
      many young RBCs as men, we investigated the effect of in vivo aging of RBCs on
      their mechanical properties. Old RBCs were shown to have an increased mechanical
      fragility and aggregability, and decreased deformability as compared to young
      RBCs. Decreased deformability and increased aggregability of RBCs cause an
      increase in blood viscosity and are known as risk factors of cardiovascular
      diseases. Since men possess a higher number of old RBCs with suboptimum
      mechanical properties than premenopausal women, who due to monthly bloodloss have
      a higher number of young cells and a lower number of old RBCs than their male
      counterparts, our results suggest that an elevated hemorheological risk for males
      is associated with the age distribution of RBCs. This, in addition to
      significantly higher hematocrit, may be the reason for the increased risk of
      morbidity and mortality from cardiovascular diseases of men as compared to women
      of reproductive age.

PMID- 9653589
TI  - An animal model to study erythrocyte senescence with a narrow time window of
      erythrocyte production.
AB  - Using the method of inducing spherocytic anemia in the rabbit with antibody
      serum, we have developed an animal model in which red blood cells (RBCs) can
      nearly grow synchronously. With this model, we determined that the surface charge
      density on the RBC membrane decreased with cell aging. The change was not linear,
      being much more profound in the latter half of RBC life span. There was a
      positive correlation between the mean RBC density and its "age" (r = 0.847, p <
      0.01). However, the density distribution of the RBCs at the same "age" showed a
      broad range, and the density values for RBC groups with different ages showed
      considerable overlap. This indicates that the density gradient technique can be
      used to separate RBC population into fractions with different mean ages, but has
      a low resolving power for obtaining individual RBCs of a given "age".

PMID- 9653590
TI  - Natural history of type 2 diabetes in Chinese. Lessons from the islands of
      Taiwan.

PMID- 9653591
TI  - Application of a diabetes managed care program. The feasibility of using nurses
      and a computer system to provide effective care.
AB  - OBJECTIVE: Treatment of patients with diabetes often falls short of recommended
      process and outcome guidelines. To improve the quality of the provided diabetes
      care, a program (the Comprehensive Diabetes Care Service [CDCS]) using a
      computerizing tracking and recall system in conjunction with nurses following
      protocols was implemented in a managed care setting. The impact of this program
      was studied and compared to the care provided to patients in another managed care
      setting. RESEARCH DESIGN AND METHODS: Patients followed in the CDCS who completed
      a diabetes education course were compared with patients followed in a group model
      health maintenance organization (GMH) who also completed a diabetes education
      course. CDCS patients received routine care in the program. GMH patients came to
      the CDCS yearly to have a diabetes evaluation. A chart review was also performed
      on their GMH outpatient records. RESULTS: Initial HbA1c levels were higher in the
      CDCS group than in the GMH group (median of 11.9 vs. 10.0%). In the CDCS
      patients, HbA1c levels not only fell significantly but were also significantly
      lower (P < 0.05) than in the GMH patients during the 2nd and 3rd year of follow
      up care. There were no significant changes in HbA1c levels in the GMH patients.
      When CDCS patients were divided into compliant and noncompliant patients, the
      median HbA1c levels in compliant patients was 8.2%, compared with 11.5% in the
      noncompliant group. The CDCS patients who needed treatment for
      hypercholesterolemia were more likely to have a lowering of their cholesterol
      levels than the GMH patients. All process measures, such as yearly measurement of
      HbA1c levels, lipid levels, and foot and retinal exams, occurred much more
      frequently in the CDCS patients. CONCLUSIONS: The system developed and
      implemented for managing diabetes improved both outcome and process measures. The
      comparison group, followed at another managed care setting, received the care
      consistent with the average (suboptimal) quality of care provided to patients
      with diabetes in the U.S. Therefore, by using innovative systems of management,
      the treatment of patients with diabetes can be greatly improved.

PMID- 9653592
TI  - Successful treatment with insulin analog lispro in IDDM with delayed absorption
      of subcutaneously applied human regular insulin and complicated intraperitoneal
      insulin infusion. A case report.
AB  - OBJECTIVE: To subcutaneously administer the insulin analog lispro in a patient
      with delayed absorption of subcutaneously applied human regular insulin whose
      continuous intraperitoneal insulin infusion (CIPII) with a percutaneous access
      device had required multiple surgical interventions because of complications.
      RESEARCH DESIGN AND METHODS: In a 35-year-old woman with long-term IDDM and
      delayed absorption of subcutaneously applied human regular insulin, a 3-year
      CIPII with human regular insulin via a percutaneous access device was complicated
      by three catheter obstructions and one subcutaneous abscess. Each complication
      required the implantation of a new percutaneous access device. During a 2-day
      trial with continuous subcutaneous insulin infusion (CSII) of the insulin analog
      lispro at basal infusion rates of 0.5-1.1 U/h, stable metabolic control was
      achieved. A 5-h intermediate attempt with human regular insulin in CSII, however,
      increased blood glucose concentrations from 6.0 to 28.8 mmol/l, despite identical
      basal rates and additional injection of 16 U of human regular insulin. Restarting
      with CSII of the insulin analog lispro reinforced stable metabolic control.
      CONCLUSIONS: It is suggested that the insulin analog lispro is a promising
      approach in the treatment of IDDM with delayed absorption of subcutaneously
      applied human regular insulin and a suitable alternative therapy for patients
      with complications attributed to percutaneous access devices for CIPII.

PMID- 9653593
TI  - Development of a scale to measure adherence to self-monitoring of blood glucose
      with latent variable measurement.
AB  - OBJECTIVE: Adherence to self-monitoring of blood glucose (SMBG) is problematic
      for many people with diabetes. Self-reports of adherence have been found to be
      unreliable, and existing paper-and-pencil measures have limitations. This study
      developed a brief measure of SMBG adherence with good psychometric properties and
      a useful factor structure that can be used in research and in practice. RESEARCH
      DESIGN AND METHODS: A total of 216 adults with diabetes responded to 30 items
      rated on a 9-point Likert scale that asked about blood monitoring habits. In part
      I of the study, items were evaluated and retained based on their psychometric
      properties. The sample was divided into exploratory and confirmatory halves.
      Using the exploratory half, items with acceptable psychometric properties were
      subjected to a principal components analysis. In part II of the study, structural
      equation modeling was used to confirm the component solution with the entire
      sample. Structural modeling was also used to test the relationship between these
      components. It was hypothesized that the scale would produce four correlated
      factors. RESULTS: Principal components analysis suggested a two-component
      solution, and confirmatory factor analysis confirmed this solution. The first
      factor measures the degree to which patients rely on others to help them test and
      thus was named "social influence." The second component measures the degree to
      which patients use physical symptoms of blood glucose levels to help them test
      and thus was named "physical influence." Results of the structural model show
      that the components are correlated and make up the higher-order latent variable
      adherence. CONCLUSIONS: The resulting 15-item scale provides a short, reliable
      way to assess patient adherence to SMBG. Despite the existence of several aspects
      of adherence, this study indicates that the construct consists of only two
      components. This scale is an improvement on previous measures of adherence
      because of its good psychometric properties, its interpretable factor structure,
      and its rigorous empirical development.

PMID- 9653594
TI  - Beginning insulin treatment of obese patients with evening 70/30 insulin plus
      glimepiride versus insulin alone. Glimepiride Combination Group.
AB  - OBJECTIVE: This study tested a simple algorithm for beginning insulin for obese
      patients with type 2 diabetes after sulfonylurea failure, comparing suppertime
      70/30 insulin plus continued glimepiride with insulin alone. RESEARCH DESIGN AND
      METHODS: This was a multicenter ambulatory randomized double-masked parallel
      comparison. There were 208 subjects with secondary failure to sulfonylureas who
      took glimepiride titrated to 8 mg b.i.d. for 8 weeks; 145 subjects with fasting
      plasma glucose (FPG) 180-300 mg/dl (10-16.7 mmol/l) on this treatment were
      randomized to placebo plus insulin (PI) or glimepiride plus insulin (GI) for 24
      weeks. A dosage of 70/30 insulin before supper was titrated, seeking fasting
      capillary blood glucose (FBG) 120 mg/dl (6.7 mmol/l), equivalent to FPG 140 mg/dl
      (7.8 mmol/l). Outcome measures included FPG, HbA1c, insulin dosage, weight, serum
      insulin and lipids, and adverse events. RESULTS: FPG and HbA1c were equivalent at
      baseline: 261 vs. 250 mg/dl (14.5 vs. 13.9 mmol/l), and 9.9 vs. 9.7%. At 24
      weeks, the FPG target was achieved in both groups (136 vs. 138 mg/dl, 7.6 vs. 7.6
      mmol/l), and HbA1c values were equal (7.7 vs. 7.6%). However, with GI, control
      improved faster and fewer subjects dropped out (3 vs. 15%, P < 0.01), and less
      insulin was needed (49 vs. 78 U/d, P < 0.001). The outcomes were alike in other
      respects. No subject had severe hypoglycemia. CONCLUSIONS: Injection of 70/30
      insulin before supper safely restored glycemic control of type 2 diabetes not
      controlled by glimepiride alone. Control was restored more rapidly and with less
      injected insulin when glimepiride was continued.

PMID- 9653595
TI  - An Asian multicenter clinical trial to assess the efficacy and tolerability of
      acarbose compared with placebo in type 2 diabetic patients previously treated
      with diet. Asian Acarbose Study Group.
AB  - OBJECTIVE: To assess the efficacy, safety, and tolerability of acarbose versus
      placebo during a 24-week treatment period in Asian type 2 diabetic patients with
      dietary failure. RESEARCH DESIGN AND METHODS: After a 6-week screening period,
      126 multiethnic Asian type 2 diabetic patients (64 men, 62 women; mean age +/-
      SD, 53.4 +/- 10 years) were randomized to receive acarbose (n = 63) or placebo (n
      = 63). The dosage was increased from 50 mg t.i.d. at week 0 to 100 mg t.i.d. at
      week 4. Patients were then followed up at weeks 10, 16, and 24. At each visit,
      body weight, blood pressure, and metabolic indexes were measured. At weeks 0 and
      24, fasting plasma glucose and insulin were measured before and 1 h after the
      administration of an individually tailored breakfast. RESULTS: Using the
      intention-to-treat analysis, there were greater reductions in (mean [95% CI])
      HbA1c (-0.70 [-1.00 to -0.39] vs. -0.27% [-0.54 to 0]; P = 0.04), fasting plasma
      glucose (-0.37 [-0.75 to 0.02] vs. 0.41 mmol/l [-0.08 to 0.90]; P = 0.017) and 1
      h plasma glucose (-0.77 [-1.44 to -0.10] vs. 0.65 mmol/l [-0.07 to 1.36]; P =
      0.05) in the acarbose group compared with the placebo group. With acarbose
      treatment, 78% of patients achieved an HbAlc < 8% compared with 56% in the
      placebo group (P = 0.003). There was a greater reduction in body weight (-1.31 [
      2.46 to -0.15] vs. 0.16 kg [-3.36 to 0.10]; P = 0.02) and higher incidence of
      flatulence (56 vs. 37%; P = 0.032) in the acarbose than in the placebo group.
      Using baseline HbA1c and race as covariates, there were no significant
      interethnic differences in treatment responses (P = 0.232 for treatment-race
      interaction; P < 0.001 for treatment effect). The dropout rates were similar
      between the two groups (acarbose, 11 of 63; placebo, 6 of 63). There were no
      significant laboratory adverse events in either group. CONCLUSIONS: In this
      multicenter study involving six ethnic groups, acarbose 100 mg t.i.d. was an
      effective, safe, and generally well-tolerated therapy in Asian type 2 diabetic
      patients with dietary failure. In some patients with troublesome gastrointestinal
      symptoms, a lower dosage may be necessary.

PMID- 9653596
TI  - Glucose metabolism, lipid metabolism, and cardiovascular risk factors in adult
      Turner's syndrome. The impact of sex hormone replacement.
AB  - OBJECTIVE: To examine glucose metabolism, blood pressure, physical fitness, and
      lipid metabolism in adult untreated women with Turner's syndrome compared with a
      group of normal women and to examine the effects of female sex hormone
      substitution on these factors. RESEARCH DESIGN AND METHODS: A total of 26
      patients with Turner's syndrome were examined before and during sex hormone
      replacement with 17 beta-estradiol and norethisterone, and an age-matched control
      group (n = 24) was examined once. A frequently sampled intravenous glucose
      tolerance test was applied with minimal model assessment. We also performed an
      oral glucose tolerance test, measurement of 24-h ambulatory blood pressure, and
      assessment of physical fitness and lipid metabolism. RESULTS: Insulin sensitivity
      (SI) and glucose effectiveness (SG) were similar in Turner's syndrome patients
      and control subjects, whereas the acute insulin response (P = 0.03) was lower in
      Turner's syndrome patients, and no change was seen during sex hormone treatment.
      Abnormal glucose tolerance was found in 50% of Turner's syndrome patients before
      and 78% during treatment with sex hormones. Fat-free mass (FFM; P = 0.0005) and
      physical fitness (P = 0.002) were lower in Turner's syndrome subjects compared
      with control subjects. During treatment, an increase in FFM (P = 0.001) and
      physical fitness (P = 0.02) was seen in Turner's syndrome patients. Blood
      pressure was increased in Turner's syndrome, and a decrease was seen in diastolic
      blood pressure during treatment with sex hormones. CONCLUSIONS: Turner's syndrome
      is associated with glucose intolerance, diminished first-phase insulin response,
      elevated blood pressure, reduced FFM, and physical fitness. Sex hormone
      administration causes a deterioration in glucose tolerance, increases FFM and
      physical fitness, and has beneficial effects on blood pressure. The deleterious
      effect on glucose tolerance may be mediated by norethisterone, a gestagen known
      to have androgenic effects.

PMID- 9653597
TI  - Multicenter study of the incidence of and predictive risk factors for diabetic
      neuropathic foot ulceration.
AB  - OBJECTIVE: To investigate longitudinally prognostic factors for foot ulceration
      in a large population of diabetic patients with established neuropathy. RESEARCH
      DESIGN AND METHODS: A double-blind multicenter study of a potential new agent for
      diabetic neuropathy provided the opportunity for this 1-year investigation since
      intervention demonstrated no efficacy in the condition. A total of 1,035 patients
      with NIDDM and IDDM were included. Inclusion criteria were vibration perception
      threshold (VPT) at the great toe > or = 25 V in at least one foot and < or = 50 V
      in both feet, normal peripheral circulation, and no previous foot ulceration. VPT
      and clinical components of the Michigan diabetic polyneuropathy (DPN) score were
      assessed at baseline and subsequent visits. RESULTS: After 1 year, the incidence
      of first foot ulcers for the total population was 7.2%. Neuropathy parameters
      were the same between the treatment and placebo groups at baseline and were
      unchanged at 1 year; therefore, baseline data were combined for multiple
      regression analysis. VPT, age, and Michigan DPN scores for muscle strength and
      reflexes were significant independent predictors for first foot ulceration (P <
      0.01). For each 1-U increase in VPT values at baseline, the hazard of the first
      foot ulcer increased by 5.6%. Similarly, for each 1-U increase in muscle strength
      and reflex components of the Michigan DPN scores, the hazard of the first foot
      ulcer increased by 5.0%. CONCLUSIONS: Tests of VPT and Michigan DPN scores for
      muscle strength and reflexes are useful clinical predictors for foot ulceration
      in diabetic patients with established neuropathy. The rate of subsequent
      ulceration in the following year was alarmingly high, however, despite
      standardized foot care education at baseline and regular follow-up visits.

PMID- 9653598
TI  - Proteinuria is still useful for the screening and diagnosis of overt diabetic
      nephropathy.
AB  - OBJECTIVE: To assess the performance of urinary total protein measurements in
      timed 24-h urine collection (24-h UP) and in a diurnal random urine specimen
      (RUS) for the screening and diagnosis of overt diabetic nephropathy. RESEARCH
      DESIGN AND METHODS: A total of 167 diabetic patients (20 type 1 and 147 type 2
      diabetic patients; 78 women and 89 men), aged 20-84 years, collected 217 timed 24
      h urine specimens. Albumin was measured by immunoturbidimetry, total protein by
      sulfosalicylic acid technique, and creatinine by Jaffe's method. According to the
      timed 24-h urinary albumin excretion rate (UAER), samples were divided into three
      groups: normoalbuminuric (NORMO) (UAER < 20 micrograms/min; n = 84),
      microalbuminuric (MICRO) (UAER 20-200 micrograms/min; n = 78), and
      macroalbuminuric (MACRO) (UAER > or = 200 micrograms/min; n = 55). Eighty-six
      patients also collected 105 RUSs (NORMO, n = 47; MICRO, n = 37; MACRO, n = 21),
      and urinary protein concentration (UPC) and urinary protein-to-creatinine ratio
      (UPCR) were measured. The receiver operating characteristics (ROC) curve approach
      was used to analyze the performance of the diagnostic tests. RESULTS: Spearman's
      coefficient of correlation of 24-h UAER versus 24-h UP was 0.95 (P < 0.001), and
      of 24-h UAER versus UPC and UPCR were 0.77 and 0.72, respectively (P < 0.001).
      The calculated areas (+/- SEM) under the ROC curve for the diagnosis of over
      diabetic nephropathy were 0.9987 +/- 0.001 for 24-h UP, 0.9926 +/- 0.006 for UPC,
      and 0.9751 +/- 0.014 for UPCR. In the ROC curves, the first points with 100%
      sensitivity were 541 mg (95.7% specificity) for 24-h UP, 431 mg/l (92.9%
      specificity) for UPC, and 0.2 (76.2% specificity) for UPCR. CONCLUSIONS:
      Measurements of proteinuria presented almost perfect accuracy for the screening
      and diagnosis of overt diabetic nephropathy. Protein measurement in spot urine is
      a reliable and simple method for the screening and diagnosis of overt diabetic
      nephropathy.

PMID- 9653599
TI  - High incidence of diabetic nephropathy in early-onset Japanese NIDDM patients.
      Risk analysis.
AB  - OBJECTIVE: Because early-onset Japanese NIDDM patients (diagnosed before age 30
      years) can develop diabetic end-stage renal failure (ESRF) in their thirties,
      this study was performed to elucidate the incidence and determinants for the
      development of diabetic nephropathy. RESEARCH DESIGN AND METHODS: The incidence
      of diabetic nephropathy and its relationship to baseline characteristics and long
      term metabolic control were determined in 426 early-onset Japanese NIDDM patients
      who were followed for a mean of 6.8 years. RESULTS: Of these 426 patients, 41
      developed diabetic nephropathy manifested by persistent proteinuria (incidence
      rate [95%CI]/1,000 person-years; 14.1 [10.4-19.1]). Among patients whose mean
      HbA1c (measured by a high-performance chromatography method that is standardized
      and comparable to the one used in the Diabetes Control and Complications Trial
      study) was around 7% or less, few developed nephropathy. The incidence of
      nephropathy increased with increasing mean HbA1c level in a dose-dependent manner
      (chi 2 trend = 49.9, P < 0.0001). Diastolic blood pressure and duration of
      diabetes at entry had significant predictive effects independent of metabolic
      control. CONCLUSIONS: The incidence rate of diabetic nephropathy in early-onset
      Japanese NIDDM patients is potentially high, similar to or higher than that in
      Pima Indian NIDDM or Caucasian IDDM patients of comparable age. Diabetic
      nephropathy in NIDDM patients aged in their thirties or forties is likely to be
      an early feature that leads to ESRF, and this would contribute to the marked
      increase in the number of new patients with diabetic ESRF in Japan. NIDDM is a
      serious disease if near-normal glycemia is not achieved.

PMID- 9653600
TI  - Asp905Tyr polymorphism of the gene for the skeletal muscle-specific glycogen
      targeting subunit of protein phosphatase 1 in NIDDM.
AB  - OBJECTIVE: To clarify the contribution of the Asp905Tyr polymorphism of the
      muscle-specific glycogen-targeting subunit of protein phosphatase 1 (PP1G) to
      insulin resistance and related diseases. RESEARCH DESIGN AND METHODS: We
      investigated the Asp905Tyr polymorphism of the PPP1R3 gene, which encodes the
      muscle-specific glycogen-targeting subunit of PP1G, in 259 Japanese patients with
      NIDDM and 194 healthy control subjects. RESULTS: No significant difference was
      found in the genotype distribution between NIDDM patients (N = 259; Asp/Asp =
      0.10, Asp/Tyr = 0.44, Tyr/Try = 0.46) and healthy control subjects (n = 194;
      Asp/Asp = 0.13, Asp/Tyr = 0.37, Tyr/Tyr = 0.50) or between patient groups
      subdivided by the mode of treatment: NIDDM patients with insulin therapy (Asp/Asp
      = 0.14, Asp/Tyr = 0.46, Tyr/Tyr = 0.40) and those without insulin therapy
      (Asp/Asp = 0.07, Asp/Tyr = 0.43, Tyr/Tyr = 0.50). However, NIDDM patients with
      the Tyr allele, which was previously reported to be associated with insulin
      resistance, tended to have lower BMIs than those without this allele (Asp/Asp:
      24.5 +/- 1.1 kg/m2, Asp/Tyr: 22.6 +/- 0.4 kg/m2, Tyr/Tyr: 22.8 + 0.3 kg/m2, P =
      0.06 by analysis of variance). CONCLUSIONS: These data suggest that the Asp905Tyr
      polymorphism of the PPP1R3 gene is not associated with NIDDM or high BMI, both of
      which are known to be insulin-resistant states, in the Japanese population.

PMID- 9653601
TI  - Diabetes in the African-American Medicare population. Morbidity, quality of care,
      and resource utilization.
AB  - OBJECTIVE: To determine whether African-American Medicare recipients with
      diabetes are at increased risk for morbidity, poor quality of care, and high
      resource utilization. RESEARCH DESIGN AND METHODS: We analyzed 1,376 patients
      with diabetes who were > or = 65 years of age and in the 1993 Medicare Current
      Beneficiary Survey. Morbidity measures were the Katz Index of Activities of Daily
      Living, Instrumental Activities of Daily Living, overall health perception,
      Charlson Comorbidity Index score, and diabetic complications. Quality of care
      standards were glycosylated hemoglobin measurements, ophthalmological visits,
      lipid testing, mammography, influenza vaccination, readmission within 30 days of
      hospital discharge, and outpatient visits within 4 weeks of hospital discharge.
      We stratified Medicare reimbursement by type of service and adjusted for sex,
      education, and age in multivariable analyses. RESULTS: Compared with white
      patients, African-American patients had worse health perception and lower quality
      of care. They were more likely to visit the emergency department and had fewer
      physician visits per year. African-Americans had higher reimbursement for home
      health services, but total reimbursement was similar after case-mix adjustment.
      CONCLUSIONS: Improved access to preventive care for older African-Americans with
      diabetes may improve health perception and use of the emergency department. The
      potential effect on total reimbursement is unclear. Future policy interventions
      to improve quality of care among Medicare patients with diabetes should
      especially target African-Americans.

PMID- 9653602
TI  - Use of the Physician Insurers Association of America database as a surveillance
      tool for diabetes-related malpractice claims in the U.S.
AB  - OBJECTIVE: To examine the available national surveillance data on malpractice
      claims associated with diabetes and to determine the medical specialties having
      the highest number of claims and the classes and costs of filed claims relating
      to diabetes. RESEARCH DESIGN AND METHODS: Data was abstracted from the Data
      Sharing Reports (DSRs) of the Physicians Insurers Association of America (PIAA),
      as well as a search of the PIAA's computerized database for the period spanning 1
      January 1985 to 31 December 1996. Data on numbers of claims, medical causes of
      loss, indemnity paid, demographics of claimants and physicians, severity, and
      medical specialties with diabetes-related claims were available. RESULTS: A total
      of 906 diabetes claims were reported to PIAA, and the total indemnity paid was
      $26,892,848. A significant downward trend (P = 0.004) was noted for the period
      between 1993 and 1996. Diabetes claimants were older and predominantly male,
      relative to all claimants. Ophthalmology, internal medicine, and general and
      family practice had the highest rates of reported claims at 16.5, 13.6, and 13.4
      diabetes claims per 1,000 claims, respectively. Of the diabetes-related injuries,
      44% occurred in the practitioners office, as compared with 27% for all claims. A
      greater proportion of diabetes claims were associated with the highest level of
      severity of injury with respect to all claims compiled by the PIAA. CONCLUSIONS:
      The database of the PIAA can be a useful resource to monitor trends in diabetes
      related malpractice. Further study into whether claims result from lack of
      adherence to practice guidelines is needed. Prevention programs designed to
      reduce the liability among high-risk specialties may also lead to improved care
      for the patient with diabetes.

PMID- 9653603
TI  - Comparison of the seasonal pattern in the clinical onset of IDDM in Finland and
      Sardinia.
AB  - OBJECTIVE: To examine the seasonal pattern for the clinical onset of IDDM in
      Finland and Sardinia, two areas where the incidence of IDDM is the highest in the
      world, and to determine the effect of climate and temperature on the clinical
      onset of IDDM. RESEARCH DESIGN AND METHODS: Analysis of seasonality for the
      diagnosis of IDDM was based on 1,405 cases in Finland and 425 cases in Sardinia
      diagnosed at < or = 14 years of age from 1989 to 1992. The average annual
      incidence of IDDM was 36.4/100,000 in Finland and 34.4/100,000 in Sardinia.
      Seasonal patterns were estimated presenting the data as short Fourier series up
      to three harmonics together with a possible linear trend. Likelihood ratio tests
      and Akaike's information criterion were used to determine the number of harmonics
      necessary to model the seasonal pattern. Seasonal patterns in both countries were
      compared between sexes and between the three 5-year age-groups, each controlling
      for the other's effect. RESULTS: In both countries, a significant seasonal
      pattern during a calendar year was found for the sexes combined and for two age
      groups (0-9 and 10-14 years). In Sardinia, two distinct cycles were found in the
      younger age-group, with a decreased incidence during May through August and an
      increased incidence during the autumn months. Two cycles were apparent in the
      older age-group, with the nadir occurring during June through September. In
      Finland, one cycle was found in the younger age-group, with a decreased incidence
      in June. In the older age-group, there were two distinct cycles, with a decreased
      incidence in June and in the September through December period. CONCLUSIONS:
      Differences between Finland and Sardinia in the seasonal pattern for the
      incidence of newly diagnosed IDDM cannot be explained by differences in climate,
      temperature, a longer warm period in Sardinia, or other climatic phenomena. The
      results do not provide evidence in favor of a specific viral etiology of IDDM. It
      may be suggested that there are triggering events at certain times, but they are
      likely to be unspecific. Nevertheless, why the incidence of IDDM in these two
      populations is equally high despite differences in climate, environment, and
      genetic background remains an unsolved question.

PMID- 9653604
TI  - Comorbidity of diabetes and eating disorders. Does diabetes control reflect
      disturbed eating behavior?
AB  - OBJECTIVE: This multicenter study was designed to explore the prevalence of
      clinical and subclinical eating disorders (EDs), the extent of intentional
      omission of insulin and oral antidiabetic agents, and its relationship to
      glycemic control in an inpatient and outpatient population of men and women with
      type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: Data have been collected
      from 12 diabetes medical centers in two German cities. In a questionnaire and
      interview-based study, a sample of male and female patients (n = 341 type 1, n =
      322 type 2) was assessed for the following eating disorders: anorexia nervosa,
      bulimia nervosa, binge eating disorder, and eating disorder not otherwise
      specified. For lack of interview data of several patients meeting the screening
      criteria, prevalence ranges were calculated. RESULTS: The overall prevalence
      range of current EDs was 5.9-8.0% (lifetime prevalence 10.3-14.0%). When patients
      were stratified according to type 1 and type 2 diabetes, there was no difference
      in prevalence of EDs. However, the distribution of the EDs was different in both
      types of diabetes, with a predominance of binge eating disorder in the type 2
      diabetes sample. Type 1 (5.9%) and type 2 (2.2%) diabetic patients reported
      deliberate omission of hyperglycemic drugs (insulin or oral agents) in order to
      lose weight. Compared with control subjects, neither the presence of EDs nor
      insulin omission influenced diabetic control. CONCLUSIONS: There seems to be no
      difference in prevalence rates of EDs in both types of diabetes; however,
      distribution of EDs is different. The findings suggest that neither EDs nor
      insulin omission are necessarily associated with poor control of glycemia. Binge
      eating disorder seems to precede type 2 diabetes in most patients and could be
      one of the causes of obesity that often precedes type 2 diabetes.

PMID- 9653605
TI  - Postmenopausal estrogens and risk of myocardial infarction in diabetic women.
AB  - OBJECTIVE: The effect of hormone replacement therapy on the risk of myocardial
      infarction in diabetic women has not been well studied. We conducted a case
      control study of postmenopausal estrogen use and risk of incident myocardial
      infarction (MI) in pharmacologically treated diabetic women enrolled at Group
      Health Cooperative of Puget Sound, a large health maintenance organization in the
      state of Washington. RESEARCH DESIGN AND METHODS: Case subjects (n = 212) were
      all postmenopausal women with treated diabetes who sustained an incident fatal or
      nonfatal MI between July 1986 and December 1994. Control subjects (n = 122) were
      treated diabetic women drawn from a stratified random sample of postmenopausal
      women without prior MI. Computerized pharmacy data and medical records were used
      to measure use of estrogens. Cardiovascular risk factors recorded from medical
      records, computerized pharmacy and laboratory data, and telephone interviews were
      used as adjustment variables. RESULTS: In this study 8.5% of case and 13.9% of
      control subjects were current users of estrogens. The relative risk (RR) of MI
      for current estrogen users was 0.51 (95% CI 0.22-1.15) relative to never users,
      adjusted for age, study year, weight, angina, and duration of treated diabetes.
      Among current estrogen users, risk of MI tended to decline with each additional
      year of estrogen use (adjusted RR = 0.78, 95% CI 0.56-1.08). Of those studied,
      45.3% of case and 37.7% of control subjects were past users of estrogens
      (adjusted RR = 1.22, 95% CI 0.71-2.09). CONCLUSIONS: This study suggests that use
      of postmenopausal estrogens does not increase risk of MI in diabetic women and
      that sustained use may be of benefit.

PMID- 9653606
TI  - Direct medical costs of complications resulting from type 2 diabetes in the U.S.
AB  - OBJECTIVE: To estimate direct medical costs of managing the complications of type
      2 diabetes. RESEARCH DESIGN AND METHODS: Costs were estimated for 15 diabetic
      complications by applying unit costs to typical resource-use profiles. Resource
      used and unit costs were estimated from many sources, including acute care
      discharge databases, clinical guidelines, government reports, fee schedules, and
      peer-reviewed literature. For each complication, the event costs are those
      associated with resource use that is specific to the acute episode and any
      subsequent care occurring in the 1st year. State costs are the annual costs of
      continued management. All costs are expressed in 1996 U.S. dollars. RESULTS: As
      expected, the more severe or debilitating events, such as acute myocardial
      infarction ($27,630 event cost; $2,185 state cost), generate a greater financial
      burden than do early-stage complications, such as microalbuminuria ($62 event
      cost; $14 state cost). Yet, complications that are initially relatively low in
      cost (e.g., microalbuminuria) can progress to more costly advanced stages (e.g.,
      end-stage renal disease, $53,659 state cost); therefore, minor complications
      should also be considered in any economic analysis of diabetes. CONCLUSIONS: The
      recent literature has lacked cost estimates that may be readily translated into
      patient-level cost inputs for an economic model. Emerging therapies that may
      reduce the incidence of some diabetic complications will need to be scrutinized
      economically in today's cost-conscious environment. The cost estimates from this
      study provide one piece of the economic analysis needed to evaluate these new
      interventional therapies.

PMID- 9653607
TI  - Association of Helicobacter pylori infection with cardiovascular and
      cerebrovascular disease in diabetic patients.
AB  - OBJECTIVE: Infection by Helicobacter pylori has been epidemiologically linked to
      some extradigestive conditions, including ischemic heart disease. Diabetic
      patients are an at-risk population for cardiovascular and thrombo-occlusive
      cerebral disease. The aim of the study was to examine a possible relationship
      between H. pylori infection and cardiovascular or cerebrovascular disease in
      diabetic patients. RESEARCH DESIGN AND METHODS: This was a cross-sectional case
      control study with 127 diabetic patients (both IDDM and NIDDM). Special emphasis
      was placed on the detection of clinical macro- and microvascular complications,
      cardiovascular risk factors, acute phase reactants, and serological markers of
      increased cardiovascular disease risk. H. pylori infection was assessed through
      the determination of specific Ig-G titers, measured by a commercial enzyme-linked
      immunosorbent assay. RESULTS: Coronary heart disease was more prevalent in
      diabetic patients with than without H. pylori (odds ratio [OR] 4.07; 95% CI 1.21
      13.6; P < 0.05). A history of thrombo-occlusive cerebral disease was also more
      frequent in H. pylori-positive diabetic patients (OR 4.8; 95% CI 1.24-18.51; P <
      0.05). Other complications such as peripheral arteriopathy, advanced nephropathy,
      neuropathy, or retinopathy were no differently distributed according to
      serological status. Alterations in the levels of the following acute-phase
      reactants and blood chemistry determinations were significantly more profound in
      H. pylori-positive diabetic patients: high fibrinogen (P < 0.05), high
      erythrocyte sedimentation rate (P < 0.001), high triglycerides (P < 0.001), and
      low HDL cholesterol (P < 0.001). There values were also more deeply altered in H.
      pylori-positive diabetic patients with a history of coronary heart disease,
      thrombo-occlusive cerebral disease, or both, when compared with H. pylori
      positive diabetic patients without those complications. CONCLUSIONS: Our data
      indicate a possible association of H. pylori infection and the development of
      coronary heart disease, thrombo-occlusive cerebral disease, or both, in diabetic
      patients. The importance of this link is highlighted by the possibility of an
      effective intervention against H. pylori infection.

PMID- 9653608
TI  - Usefulness of revised fasting plasma glucose criterion and characteristics of the
      insulin response to an oral glucose load in newly diagnosed Japanese diabetic
      subjects.
AB  - OBJECTIVE: To examine the usefulness of the revised criterion for fasting plasma
      glucose (FPG) in the diagnosis of diabetes recommended by the American Diabetic
      Association (ADA) (126 mg/dl, 7 mmol/l), and to characterize insulin response
      during the 75-g oral glucose tolerance test (OGTT) in newly diagnosed Japanese
      diabetic subjects. RESEARCH DESIGN AND METHODS: A series of 2,121 Japanese
      subjects underwent a 75-g OGTT (0-3 h) and were divided into three groups (normal
      glucose tolerance [NGT], impaired glucose tolerance [IGT], and diabetes mellitus
      [DM] according to the current World Health Organization criteria. After the
      cutoff values of FPG that distinguish NGT and IGT from diabetes were analyzed,
      the usefulness of the ADA criterion for FPG was examined by comparing diagnostic
      parameters (sensitivity, specificity, and accuracy) with those for the cutoff
      value of 140 mg/dl. To assess insulin response, both the insulinogenic index
      (IsIx), a marker of early secretion, and the area under the insulin response
      curve (AUCins), a marker of total secretion, were compared between the DM, NGT,
      and IGT groups. RESULTS: First, the FPG cutoff value distinguishing NGT from
      diabetes was 109 mg/dl. An FPG of 126 mg/dl showed a higher sensitivity (0.52 vs.
      0.31), the same specificity (1.00), and a higher accuracy (0.82 vs. 0.74) than an
      FPG of 140 mg/dl, and it had a higher specificity (1.00 vs. 0.86) with a slightly
      lower accuracy (0.82 vs. 0.85) than an FPG of 109 mg/dl. Second, the FPG cutoff
      value differentiating IGT from diabetes was 113 mg/dl. An FPG of 126 mg/dl showed
      a higher sensitivity (0.52 vs. 0.31) and accuracy (0.80 vs. 0.74) and a similar
      specificity (0.97 vs. 1.00) compared with an FPG of 140 mg/dl, and it had a
      higher specificity (0.97 vs. 0.82) with the same accuracy (0.80) as an FPG of 113
      mg/dl. Third, the DM group showed the lowest IsIx among the three groups at all
      FPG values. The AUCIns in the DM group increased along with FPG, reached the
      maximum level at an FPG of 110 mg/dl, and declined thereafter. AUCIns was higher
      in the DM group than in the NGT group at FPG values > or = 100 mg/dl.
      CONCLUSIONS: The revised ADA criterion for FPG of 126 mg/dl may improve
      diagnostic sensitivity without loss of specificity in Japanese diabetic subjects
      when compared with an FPG criterion of 140 mg/dl. Although early insulin
      secretion was impaired, total insulin secretion did not seem to be reduced in
      newly diagnosed Japanese diabetic subjects.

PMID- 9653609
TI  - Mortality in adults with and without diabetes in a national cohort of the U.S.
      population, 1971-1993.
AB  - OBJECTIVE: To examine 22-year mortality (1971-1993), causes of death, life
      expectancy, and survival in a national sample of diabetic and nondiabetic adults
      according to age, sex, and race. RESEARCH DESIGN AND METHODS: A representative
      national cohort of 14,374 adults aged 25-74 years was identified in 1971-1975 in
      the First National Health and Nutrition Examination Survey (NHANES I). Diabetes
      was ascertained by medical history interview. The cohort was followed for
      mortality through 1992-1993, with verification of vital status for 96.2% (n =
      13,830). Causes of death were determined from death certificates. RESULTS:
      Diabetic subjects comprised 5.1% of the cohort and accounted for 10.6% of the
      deaths. Mortality for diabetic subjects increased from 12.4 per 1,000 person
      years for those aged 25-44 years at baseline to 89.7 per 1,000 person-years for
      those aged 65-74 years. The age-adjusted mortality rate was 57% higher for
      diabetic men than for diabetic women; the rate was 27% higher for diabetic non
      Hispanic blacks than for diabetic non-Hispanic whites. Mortality rates were
      highest for insulin-treated subjects and for those with > or = 15 years' duration
      of diabetes. Diabetes was listed on the death certificate as the underlying cause
      of death for only 7.7% of diabetic men and 13.4% of diabetic women. Considering
      multiple causes of death, heart disease was listed the most frequently and was
      present on 69.5% of death certificates of people with diabetes. Death rates were
      higher for diabetic than for nondiabetic subjects in all age, sex, and race
      groups. The relative risk of death (diabetic versus nondiabetic subjects)
      declined with age from a value of 3.6 for those aged 25-44 years at baseline to
      1.5 for those aged 65-74 years. The relative risk was elevated in diabetic
      subjects for all major causes of death except malignant neoplasms. Survival of
      diabetic subjects was lower than that of nondiabetic subjects in all age, sex,
      and race groups. Median life expectancy was 8 years lower for diabetic adults
      aged 55-64 years and 4 years lower for those aged 65-74 years. CONCLUSIONS: In
      this representative national sample of adults, mortality rates were higher for
      diabetic men than for diabetic women and for diabetic blacks than for diabetic
      whites. The study confirms the substantially higher risk of death, lower
      survival, and lower life expectancy of diabetic adults compared with nondiabetic
      adults.

PMID- 9653610
TI  - Factors associated with glycemic control. A cross-sectional nationwide study in
      2,579 French children with type 1 diabetes. The French Pediatric Diabetes Group.
AB  - OBJECTIVE: To determine on a large scale the multiple medical and nonmedical
      factors that influence glycemic control in the general population of children
      with diabetes, we performed a nationwide French cross-sectional study. RESEARCH
      DESIGN AND METHODS: We enrolled 2,579 patients aged 1-19 years with type 1
      diabetes of > 1 year's duration. The study was center based: 270 centers were
      identified, 206 agreed to participate, and 147 included at least 90% of their
      patients. Questionnaires were completed by physicians interviewing patients and
      family, and HbA1c measurements were centralized. To identify explanatory
      variables for HbA1c level and frequency of severe hypoglycemia, we performed
      multiple regression analysis using all the quantitative variables collected and
      stepwise logistic regression for the qualitative variables. RESULTS: Mean HbA1c
      value for the whole population was 8.97 +/- 1.98% (normal 4.7 +/- 0.7% [SD]).
      Only 19 children (0.7%) had ketoacidosis during the 6 months before the study,
      whereas 593 severe hypoglycemia events occurred in 338 children (13.8%). Control
      was better in university-affiliated hospitals and centers following > 50
      patients, reflecting the importance of access to experienced diabetologists.
      Children had a mean of 2.3 injections, allegedly performed 2.8 glucose
      measurements per day, and were seen an average of 4.6 times per year at the
      center. In the multiple regression analysis, 94% of the variance of HbA1c was
      explained by our pool of selected variables, with the highest regression
      coefficient between HbA1c and age (Rc = 0.43, P < 0.0001), then with daily
      insulin dosage per kilogram (Rc = 0.28, P < 0.0001), mother's age (Rc = 0.26, P <
      0.0001), frequency of glucose measurements (Rc = 0.21, P < 0.0001), and diabetes
      duration (Rc = 0.14, P < 0.0001). Logistic regression identified quality of
      family support and dietary compliance, two related qualitative and possibly
      subjective variables, as additional explanatory determinants of HbA1c. The
      frequency of severe hypoglycemia was 45 per 100 patient-years and correlated with
      diabetes duration, but not with HbA1c levels or other variables. CONCLUSIONS:
      Although overall results remain unsatisfactory, 33% of studied French children
      with type 1 diabetes had HbA1c < 8%, the value obtained in Diabetes Control and
      Complications Trial adolescents treated intensively. Diabetes management in
      specialized centers should be encouraged.

PMID- 9653612
TI  - Rigiscan evaluation of specific nervous impairment in patients with diabetes and
      erectile disorders.
AB  - OBJECTIVE: A proposed new, minimally invasive, and painless method for studying
      impairment of the autonomic system of the penile region in type 2 diabetes
      patients. RESEARCH DESIGN AND METHODS: Thirteen subjects were selected from 150
      patients with type 2 diabetes and erectile dysfunction who were studied in
      accordance with the National Institutes of Health consensus. The 13 subjects
      (group A), aged 55 +/- 8 years, had acceptable metabolic control (HbA1c, < 8%);
      no arterial or venous diseases or initial Peyronie's disease, as evaluated by
      penile Doppler ultrasonography and intracavernous prostaglandin E1 injection; and
      penile tumescence at the base (PTB) < 30 mm. Group B consisted of 13 control
      subjects with the same characteristics, including mean age (53.1 +/- 9 years),
      metabolic control (HbA1c, 7.3 +/- 0.7%), and duration of disease (8.3 +/- 0.7
      years), but PTB was > 30 mm. Student's t test was used to evaluate differences in
      the results of autonomic cardiovascular tests, somatic tests (vibration
      perception threshold [VPT]), and diabetic neuropathy score (DNS) in both groups.
      The coefficient of variation of PTB was evaluated using the Rigiscan device
      (Dacomed, Minneapolis, MN), and Bayes' test was used to test sensitivity,
      specificity, and positive predictive values of the cardiovascular tests. RESULTS:
      Patients with PTB < 30 mm had significant (P < 0.05) impairment of
      parasympathetic tests (lying to standing, P < 0.02; standing to lying, P < 0.04;
      squat test, P < 0.03) compared with subjects with higher PTB values. No
      difference in DNS and VPT at the base and tip of the penis was found between the
      two groups. The variability of the test is 10% in normal subjects and 15% in both
      groups of patients. PTB sensitivity was 54%, specificity 89%, and positive
      predictive value 79%. CONCLUSIONS: In patients with diabetes and without vascular
      diseases, the PTB evaluated by Rigiscan is related to impairment of the autonomic
      nervous system. A PTB value < 30 mm may be considered a useful, noninvasive
      marker in studying parasympathetic damage of the penile region.

PMID- 9653611
TI  - Acarbose in NIDDM patients with poor control on conventional oral agents. A 24
      week placebo-controlled study.
AB  - OBJECTIVE: To determine the efficacy of acarbose, compared with placebo, on the
      metabolic control of NIDDM patients inadequately controlled on maximal doses of
      conventional oral agents. RESEARCH DESIGN AND METHODS: In this three-center
      double-blind study, 90 Chinese NIDDM patients with persistent poor glycemic
      control despite maximal doses of sulfonylurea and metformin were randomly
      assigned to receive additional treatment with acarbose 100 mg thrice daily or
      placebo for 24 weeks, after 6 weeks of dietary reinforcement. Efficacy was
      assessed by changes in HbA1c, fasting and 1-h postprandial plasma glucose and
      insulin levels, and fasting lipid levels. RESULTS: Acarbose treatment was
      associated with significantly greater reductions in HbA1c (-0.5 +/- 0.2% vs.
      placebo 0.1 +/- 0.2% [means +/- SEM], P = 0.038), 1-h postprandial glucose (-2.3
      +/- 0.4 mmol/l vs. placebo 0.7 +/- 0.4 mmol/l, P < 0.001) and body weight (-0.54
      +/- 0.32 kg vs. placebo 0.42 +/- 0.29 kg, P < 0.05). There was no significant
      difference between the two groups regarding changes in fasting plasma glucose and
      lipids or fasting and postprandial insulin levels. Flatulence was the most common
      side effect (acarbose vs. placebo: 28/45 vs. 11/44, P < 0.05). One patient on
      acarbose had asymptomatic elevations in serum transaminases that normalized in 4
      weeks after acarbose withdrawal. Another patient on acarbose developed severe
      hypoglycemia; glycemic control was subsequently maintained on half the baseline
      dosage of sulfonylurea. CONCLUSIONS: In NIDDM patients inadequately controlled on
      conventional oral agents, acarbose in moderate doses resulted in beneficial
      effects on glycemic control, especially postprandial glycemia, and mean body
      weight. Additional use of acarbose can be considered as a useful alternative in
      such patients if they are reluctant to accept insulin therapy.

PMID- 9653614
TI  - Effects of diabetes and level of glycemia on all-cause and cardiovascular
      mortality. The San Antonio Heart Study.
AB  - OBJECTIVE: Although the level of hyperglycemia is clearly a risk factor for
      microvascular complications in diabetic patients, its role in macrovascular
      complications remains controversial. We followed 4,875 subjects (65% Mexican
      American) for 7-8 years to investigate the effects of diabetes and hyperglycemia
      on all-cause and cardiovascular disease (CVD) mortality. These end points were
      also analyzed according to quartiles of baseline fasting plasma glucose among
      diabetic participants. RESEARCH DESIGN AND METHODS: The Cox proportional hazards
      model was used to estimate the relative risks (RRs) for all-cause and CVD
      mortality. RESULTS: Diabetes was significantly associated with increased all
      cause mortality (RR [95% CI] = 2.1 [1.3-3.5] in men; 3.2 [1.9-5.4] in women) and
      increased CVD mortality (3.2 [1.4-7.1] in men; 8.5 [2.8-25.2] in women). Among
      diabetic subjects, those in quartile 4 had a 4.2-fold greater risk of all-cause
      mortality (P < 0.001) and a 4.7-fold greater risk of CVD mortality (P = 0.01)
      than those in quartiles 1 and 2 combined. After further adjustment for other
      potential risk factors, subjects in quartile 4 had a 4.9-fold greater risk of all
      cause mortality and a 4.9-fold greater risk of CVD mortality than those in
      quartiles 1 and 2. In addition, hypertension, current smoking, and cholesterol >
      6.2 mmol/l were significant predictors of CVD mortality using Cox models.
      CONCLUSIONS: We conclude that diabetes is a predictor of both all-cause and CVD
      mortality in the general population and that both hyperglycemia and common CVD
      risk factors are important predictors of all-cause and CVD mortality in diabetic
      subjects.

PMID- 9653613
TI  - Optimization of evening insulin dose in patients using the short-acting insulin
      analog lispro.
AB  - OBJECTIVE: A three-way, crossover, open-label, randomized study was designed to
      compare the evening and night (1800-0800) glycemic control when the evening
      premeal lispro dose was reduced by 20% and the bedtime basal NPH dose increased
      by 25%, or when the basal NPH dose was moved to before dinner at 1800, compared
      with the control arm on standard premeal human regular insulin and pre-bedtime
      NPH insulin. RESEARCH DESIGN AND METHODS: A total of 13 type 1 diabetic patients
      who use a premeal plus basal insulin regimen were studied on three separate days,
      with identical meals and snacks at the same times on each study day. On the
      control study day, patients received human regular insulin before dinner and NPH
      at bedtime in their usual doses. On another day, lispro was given before dinner
      with a dose reduction of 20%, and NPH at bedtime at 125% of usual dose. In the
      third regimen, the lispro and NPH were administered together in their usual dose
      before the evening meal by separate injections. The three regimens were tested in
      random order. RESULTS: Postprandial (1800-2200) blood glucose concentrations were
      lower after reduced-dose lispro compared with human regular insulin (6.0 +/- 0.3
      [SEM] vs. 7.4 +/- 0.3 mmol/l, P < 0.05). Nighttime (2400-0400) blood glucose
      concentrations were not different (8.6 +/- 0.3 vs. 9.2 +/- 0.3 mmol/l, NS), and
      prebreakfast concentrations were also unchanged (7.7 +/- 0.9 vs. 8.7 +/- 0.8
      mmol/l) after lispro with increased-dose NPH compared with standard insulin. By
      contrast, both nighttime (10.0 +/- 0.3 mmol/l, P < 0.05) and fasting glucose
      concentrations (10.8 +/- 0.6 mmol/l, P < 0.05) were significantly higher with
      dinnertime usual-dose lispro plus dinnertime usual-dose NPH compared with
      standard human insulin. Hypoglycemia at night (blood glucose < 3.0 mmol/l) did
      not differ between study days, but it was more frequent postprandially after
      dinner usual-dose lispro plus early NPH (2 vs. 7 patients, P = 0.062).
      CONCLUSIONS: With lower mealtime and higher basal bedtime insulin doses, patients
      using insulin lispro may be able to gain an overall improvement in evening blood
      glucose control without deteriorated nighttime glucose levels. Earlier basal NPH
      dosage alone does not ameliorate the nighttime hyperglycemia of short-acting
      insulin analog regimens.

PMID- 9653615
TI  - Power spectral analysis of heart rate variation in diabetic patients with
      neuropathic foot ulceration.
AB  - OBJECTIVE: To evaluate the relationship between diabetic autonomic neuropathy and
      diabetic neuropathic foot ulceration, we used power spectral analysis (PSA) of
      heart rate variation, which provides the accurate simultaneous quantification of
      parasympathetic and sympathetic activities, to assess autonomic function in
      diabetic patients. RESEARCH DESIGN AND METHODS: We studied 55 NIDDM patients
      including 10 diabetic patients without neuropathy, 23 diabetic patients with
      neuropathy and no history of foot ulceration, and 22 diabetic patients with
      neuropathic foot ulceration. We performed PSA of 100 R-R intervals at rest and
      analyzed the results by fast Fourier transformation. RESULTS: The low frequency
      (LF) power, which reflects sympathetic activity, and the high frequency (HF)
      power, which reflects parasympathetic (vagal) activity, were inversely correlated
      with the duration of diabetes and the fasting plasma glucose (FPG) levels. By
      multiple regression analysis, the FPG remained with significant influence on both
      LF and HF powers. The LF and HF powers were positively correlated with motor
      nerve conduction velocity (MCV) and sensory nerve conduction velocity (SCV) in
      the upper and lower limbs and the coefficient of variation of R-R intervals. The
      LF and HF powers were significantly reduced in patients with neuropathy and
      patients with foot ulceration compared with patients without neuropathy. Although
      the median MCV and SCV were similar between diabetic patients with neuropathy and
      patients with foot ulceration, both the LF and HF powers were significantly
      decreased in patients with foot ulceration compared with patients with
      neuropathy. There was no difference in the value of the LF:HF ratio, an index of
      sympathovagal balance, among three subgroups. We observed a positive correlation
      between LF and HF power in all subjects; however, the LF and HF powers were not
      correlated in the subgroups of patients with foot ulceration. CONCLUSIONS: These
      results showed that diabetic patients with neuropathic foot ulceration have a
      greater impairment in spectral indexes of autonomic activity obtained by PSA than
      patients with neuropathy and no history of foot ulceration, whereas no difference
      was present in nerve conduction velocities.

PMID- 9653616
TI  - Stiffness indexes beta of the common carotid and femoral arteries are associated
      with insulin resistance in NIDDM.
AB  - OBJECTIVE: To investigate the association between arterial wall stiffness indexes
      beta of the common carotid artery (CCA) and the femoral artery (FA) and insulin
      resistance in NIDDM subjects in a cross-sectional study. RESEARCH DESIGN AND
      METHODS: We evaluated the arterial stiffness indexes beta of CCA and FA using an
      ultrasonic phase-locked echo-tracking system in 60 NIDDM subjects attending the
      diabetes center in Osaka City University Hospital, compared with 120 age- and sex
      matched control subjects. Insulin sensitivity indexes were evaluated using a
      euglycemic-hyperinsulinemic clamp. RESULTS: Stiffness indexes beta of both CCA
      and FA were significantly higher in NIDDM subjects than in control subjects (CCA
      18.1 +/- 0.9 vs. 11.7 +/- 0.3, respectively, P < 0.001; FA 35.7 +/- 2.3 vs. 23.7
      +/- 0.8, respectively, P < 0.001). The mean insulin sensitivity index in NIDDM
      subjects was 4.69 +/- 0.29 mg.kg-1.min-1.mU-1.l. The stiffness indexes beta of
      both CCA and FA were inversely correlated with insulin sensitivity indexes (CCA r
      = -0.393, P = 0.002; FA r = -0.329, P = 0.010), as well as with age, duration of
      diabetes, and mean blood pressure. In stepwise multiple regression analyses,
      insulin sensitivity index and duration of diabetes were identified as significant
      independent variables for stiffness indexes beta in both CCA and FA (CCA R2 =
      0.249, P = 0.0003; FA R2 = 0.336, P < 0.001). CONCLUSIONS: Arterial stiffness
      indexes beta of CCA and FA were associated with insulin resistance in NIDDM
      subjects.

PMID- 9653617
TI  - Progression to type 2 diabetes among high-risk groups in Kin-Chen, Kinmen.
      Exploring the natural history of type 2 diabetes.
AB  - OBJECTIVE: To examine the natural history of 654 high-risk subjects (340 men and
      314 women) with fasting hyperglycemia (first fasting plasma glucose [FPG] level
      5.6-7.8 mmol/l) who also exhibited 2-h postload glucose concentrations < 11.1
      mmol/l and an FPG level < 7.8 mmol/l in a 75-g oral glucose tolerance test
      (OGTT). We were particularly interested in comparing the likelihood of developing
      type 2 diabetes for those with persistent fasting hyperglycemia (PFH), impaired
      glucose tolerance (IGT), and normal glucose tolerance (NGT). PFH is a relatively
      new definition, and those with PFH used to be defined as NGT according to WHO
      criteria. RESEARCH DESIGN AND METHODS: Subjects were located in a 1992-1994
      community-based population survey and followed up and reexamined during 1995
      1996. An OGTT was used to determine who had progressed to type 2 diabetes. Risk
      factors predictive of subsequent progression to type 2 diabetes were determined
      by comparing baseline variables from the 1992-1994 survey with data of those who
      had or had not progressed to type 2 diabetes in 1995-1996. RESULTS: Of 654 high
      risk subjects screened in the baseline survey, 481 (73.5%, 255 men and 226 women)
      were followed up. Of these, 8.1% had progressed to diabetes (4.1%
      progression/year, 95% CI 2.3-5.9). Of 131 baseline IGT subjects, 17.6% progressed
      to diabetes (8.8% progression/year, 6.3-11.3), but only 7.4% of 95 PFH subjects
      (3.7% progression/year, 2.0-5.4) and 3.5% of 255 NGT subjects (1.8%
      progression/year, 0.1-3.0) progressed to diabetes. CONCLUSIONS: The rates of
      progression to type 2 diabetes were lowest from the NGT subgroup, highest from
      the IGT group, with the PFH group in the middle, suggesting that PFH might be a
      transitional condition that precedes IGT and diabetes. Other significant
      predictors of subsequent diabetes were baseline BMI, baseline hyperuricemia,
      baseline FPG, and 2-h plasma glucose concentration.

PMID- 9653618
TI  - Hyperinsulinemia and carotid atherosclerosis in hypertensive and control
      subjects.
AB  - OBJECTIVE: To analyze the relationships between carotid atherosclerosis measured
      as intima-media thickness (IMT) and different measures of insulin in a population
      based case-control study of men and women. RESEARCH DESIGN AND METHODS: Carotid
      ultrasonographic measurements and 2-h oral glucose tolerance tests were performed
      in a random sample of 513 hypertensive subjects, aged 40-59 years, and in 518 age
      and sex-matched control subjects. The associations between IMT and the different
      measures of insulin were analyzed through multiple regression and by insulin
      quintiles. The independent effect of insulin was estimated after concurrent
      adjustment for age, obesity, LDL cholesterol, and systolic blood pressure.
      RESULTS: The most powerful correlates with IMT were LDL cholesterol, age,
      systolic blood pressure, pack-years of smoking, and of the different insulin
      parameters, 2-h post-load insulin. In stepwise regression analysis, the
      independent predictors of the mean IMT were LDL cholesterol, systolic blood
      pressure, pack-years of smoking, and age (P < 0.0001) after adjustment for the
      independent predictors. In analysis of variance, no positive association of
      insulin parameters with IMT was found between the 2-h insulin quintiles after
      adjustment for the independent variables. The exclusion of diabetic subjects did
      not change the results. CONCLUSIONS: The present study of a population-based
      sample of men and women found inconsistent associations between different insulin
      measures and IMT after adjustment for the independent variables.

PMID- 9653619
TI  - Glucokinase gene islet promoter region variant (G-->A) at nucleotide -30 is not
      associated with reduced insulin secretion in Finns.
AB  - OBJECTIVE: To investigate the effect of the islet promoter region variant (G-->A)
      at nucleotide -30 of the glucokinase (GCK) gene on insulin levels in subjects
      with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and NIDDM.
      RESEARCH DESIGN AND METHODS: The study population included 294 subjects with NGT,
      83 subjects with IGT, and 36 subjects with NIDDM. Oral glucose tolerance tests
      (OGTTs) were performed in all subjects, and intravenous glucose tolerance tests
      (IVGTTs) were performed in subjects with NGT. The islet promoter region of the
      GCK gene was amplified with polymerase chain reaction and screened for the
      variant (-30) using single-strand conformation polymorphism analysis. RESULTS:
      The islet promoter variant (-30) of the GCK gene was found in 17% of subjects
      with NGT, 23% of subjects with IGT, and 14% of patients with NIDDM (NS between
      the groups). Fasting, 1-h, and 2-h insulin levels, measured by OGTT, did not
      differ between subjects with and without this variant in any of the three groups.
      Furthermore, first-phase insulin secretion, determined by an IVGTT in subjects
      with NGT, did not associate with presence of the islet promoter region variant (
      30) of the GCK gene. CONCLUSIONS: These results indicate that the variant (-30)
      of the islet promoter region of the GCK gene does not have a significant effect
      on insulin secretion in Finnish subjects with NGT, IGT, or NIDDM.

PMID- 9653620
TI  - International Diabetes Federation meeting, 1997. Neuropathy, information
      technology, cost of diabetes care, and epidemiology.

PMID- 9653621
TI  - Factor V Leiden (F5 Q506) and vascular disease in Canadian Oji-Cree.

PMID- 9653622
TI  - Health-related quality of life and insulin lispro. A naturalistic approach.

PMID- 9653623
TI  - Influence of sex differences in subcutaneous fat mass on serum leptin
      concentrations.

PMID- 9653624
TI  - A simple device for foot pressure measurement. Evaluation in south Indian NIDDM
      subjects.

PMID- 9653625
TI  - The efficacy of voglibose on glycemic excursions in non-insulin-treated NIDDM
      patients.

PMID- 9653626
TI  - Freeze-drying of bioproducts: putting principles into practice.
AB  - The product and process parameters that determine successful freeze-drying are
      described and their interrelationships are explored. It is shown that the
      thermochemical and thermomechanical properties of water-soluble, amorphous
      materials form the basis of effective formulation design and that coordinated
      approaches to formulation and process development achieve optimum results with a
      minimum of trial-and-error experimentation.

PMID- 9653627
TI  - Application of infrared spectroscopy to development of stable lyophilized protein
      formulations.

PMID- 9653628
TI  - Water vapor sorption by peptides, proteins and their formulations.
AB  - The interactions of pharmaceutical peptides, proteins and their formulations with
      environmental water vapor are reviewed. Particular attention is paid to the
      importance of the physical structure and chemical diversity of peptides and
      proteins, and comparisons are made with the mechanisms of water vapor sorption by
      synthetic macromolecular systems. The influences of formulation processes and
      additives are also considered and suggestions made for future areas of research.

PMID- 9653630
TI  - Sustained release of injectable zinc-recombinant hirudin suspensions: development
      and validation of in vitro release model.
AB  - In humans, recombinant hirudin (rHir), an anticoagulant protein, has a relatively
      short half-life (about 1 h). Therefore, a rHir formulation with sustained
      biological activity was previously proposed to result from complexing zinc salts
      and rHir (Zn-rHir). The purpose of this paper is to introduce and validate an in
      vitro release model for subcutaneous Zn-rHir formulations. In glass vials the
      formulations were suspended in agarose gel (2%) and coated with an extra layer of
      protein-free agarose. The agarose layers were covered with receiver solution,
      either buffered solutions (HEPES or PBS, pH 7.4) or human serum. To validate the
      release model and to demonstrate its potential to discriminate between different
      formulations, several commercial insulin and Zn-insulin formulations were also
      tested. The release profiles were evaluated by statistical moment analysis (mean
      times). Only in HEPES buffer was good discrimination between the investigated
      insulin formulations observed. The mean times of in vitro release of the insulin
      formulations and the proposed duration of their biological activities were in
      correlation. Low discrimination was found in PBS. For rHir, clear discrimination
      between the investigated rHir formulations was achieved in HEPES buffer, whereas
      low discrimination was found in PBS or in serum. The developed release model may
      be a sensitive in vitro test to assure the quality of subcutaneous insulin and
      rHir formulations, and may also be applicable to assess other slow-release
      protein and low molecular weight drug injectables.

PMID- 9653629
TI  - Effect of process conditions on recovery of protein activity after freezing and
      freeze-drying.
AB  - The objective of this research was to gain a better understanding of the degree
      to which recovery of activity of model proteins after freeze-drying can be
      maximized by manipulation of freeze-dry process conditions in the absence of
      protective solutes. Catalase, beta-galactosidase and lactate dehydrogenase (LDH)
      were used as model proteins. All of the three proteins exhibited a concentration
      dependent loss of activity after freezing, with significantly higher recovery at
      higher concentration. The freezing method and the type of buffer were also
      important, with sodium phosphate buffer and freezing by immersion of vials in
      liquid nitrogen associated with the lowest recovery of activity. Differential
      scanning calorimetry was predictive of the onset of collapse during freeze-drying
      only for beta-galactosidase. For the other proteins, either no Tg' transition was
      observed, or the apparent glass transition did not correlate with the
      microscopically-observed collapse temperature. The time course of activity loss
      for beta-galactosidase and LDH was compared during freeze-drying under conditions
      which produced collapse of the dried matrix and conditions which produced
      retention of microstructure in the dried solid. Recovery of activity decreased
      continuously during primary drying, with no sharp drop in recovery of activity
      associated with the onset of collapse. The most important drying process variable
      affecting recovery of activity was residual moisture level, with a dramatic drop
      in activity recovery associated with residual moisture levels less than about
      10%.

PMID- 9653631
TI  - Labelling peptides with fluorescent probes for incorporation into degradable
      polymers.
AB  - Two peptides, atrial natriuretic peptide (ANP) and salmon calcitonin (sCT) were
      conjugated with a fluorescent, amine-reactive probe 5-(and 6
      )carboxytetramethylrhodamine,-succinimidylester (5-(6)-TAMRA-SE). The labelling
      reaction was followed by HPLC and found to be complete after 2 h. The labelled
      peptides were purified by gel filtration chromatography and characterised by
      [1H]NMR, UV/VIS and fluorescence spectroscopy. NMR-spectra confirmed the
      conjugation of dye to the peptides. Two absorption maxima between 500 and 600 nm
      were recorded in the UV/VIS-spectra. The fluorescence spectra were found to be pH
      dependent, which allowed the measurement of pH in aqueous solution. The labelled
      peptides were encapsulated into poly(lactic acid) (PLA) microspheres using a
      double emulsion technique. Probe attachment permitted location of the peptides in
      the polymer.

PMID- 9653632
TI  - Fibronectin-binding peptides. I. Isolation and characterization of two unique
      fibronectin-binding peptides from gelatin.
AB  - Gelatin binds to fibronectin with a high affinity although the fibronectin
      binding components have not been located. Fibronectin plays an important role in
      tumor cell metastasis and gelatin may have a profound effect on the metastatic
      process. In this study, fractionated acid-washed gelatin was cleaved with trypsin
      and resultant peptides fractionated by fibronectin-Sepharose affinity
      chromatography. After further purification using size exclusion HPLC and then
      reverse-phase HPLC, two unique peptides were obtained and sequenced. The binding
      affinities of these two peptides to fibronectin were evaluated by an ELISA method
      developed during this study and compared with the gelatin. Both possessed
      significantly higher binding affinities to fibronectin than gelatin alone.

PMID- 9653633
TI  - Protein encapsulation and release from poly(lactide-co-glycolide) microspheres:
      effect of the protein and polymer properties and of the co-encapsulation of
      surfactants.
AB  - Despite the recognised role of the poly(lactide-co-glycolide) (PLGA) in the
      encapsulation and release of proteins from PLGA microspheres, the importance that
      the characteristics of the protein have in these processes has not yet been
      sufficiently investigated. The aim of this work was to study the simultaneous
      effect of the protein and PLGA properties and of the microencapsulation process
      on the physicochemical and in vitro release characteristics of protein-loaded
      PLGA microspheres. Two model proteins of different isoelectric points (pI),
      bovine serum albumin (BSA) (pI = 4.6) and lysozyme (LZM) (pI = 11.2), and two
      different molecular weights (Mw) of PLGA were selected. Microspheres were
      prepared using the water-in-oil-in-water (w/o/w) solvent extraction and the oil
      in-oil (o/o) solvent evaporation techniques. Results showed that BSA was
      efficiently encapsulated independent of the PLGA Mw, whereas the encapsulation of
      LZM was favoured with the low Mw PLGA. The co-encapsulation of a surfactant
      (poloxamer 188 or 331) reduced the protein encapsulation efficiency, especially
      of BSA. These results suggested that the tensoactive properties of the protein
      and its affinity for the PLGA are major determinants of the protein
      encapsulation. Both proteins released faster from the microspheres prepared by
      the o/o solvent evaporation procedure, with respect to those prepared by the
      w/o/w solvent extraction technique. In addition, both polymer Mw and protein type
      had an effect on the protein release rate. The release rate of both proteins, in
      the absence of a surfactant, was faster from the low Mw PLGA microspheres.
      However, the release rate constant was higher for BSA than for LZM irrespective
      of the PLGA Mw. In addition, the co-encapsulation of a surfactant led, in most
      cases, to a faster release of the encapsulated protein. To conclude, these
      results suggest that protein release from PLGA microspheres is not only governed
      by the PLGA erosion rate and protein diffusion through the water-filled channels,
      but is highly affected by the protein properties and its possible interaction
      with PLGA and its degradation products.

PMID- 9653634
TI  - Recombinant human erythropoietin (rhEPO) loaded poly(lactide-co-glycolide)
      microspheres: influence of the encapsulation technique and polymer purity on
      microsphere characteristics.
AB  - Recombinant human erythropoietin (EPO) and fluorescein isothiocyanate-labelled
      dextran (FITC-dextran) loaded biodegradable microspheres were prepared from
      poly(lactide-co-glycolide) (PLG) by a modified spray-drying technique. This
      microencapsulation method was compared with the water-in-oil-in-water (w/o/w)
      double-emulsion method. As expected, microsphere morphology, particle size and
      particle size distribution strongly depended on the production process. The spray
      drying method was found to have a number of advantages compared to the w/o/w
      double-emulsion technique. The content of residual dichloromethane (DCM) in the
      final product was significantly lower in case of the microspheres prepared by
      spray-drying. Concerning EPO loaded microspheres, spray-drying yielded higher
      encapsulation efficiencies. Although the microspheres obtained by spray-drying
      are subjected to intensive mechanical and thermal stress during the preparation,
      the amount of aggregates of EPO in PLG microspheres were not increased compared
      to the w/o/w technique. Depending on the manufacturing method, addition of cyclic
      DL-lactide dimers (referred to as monomers in the following) affected the in
      vitro release profiles of EPO and FITC-dextran from PLG microspheres. Using
      differential scanning calorimetry it was shown that these low molecular weight
      substances only seem to be present inside the microspheres produced by spray
      drying. DL-Lactide significantly reduced the initial burst release of both EPO
      and FITC-dextran. While the following release period of EPO was not affected by
      the DL-lactide content, a more linear FITC-dextran release pattern could be
      achieved. It can be concluded that the spray-drying technique provides a number
      of advantages compared to the w/o/w method. The modulation of protein release
      using low molecular weight additives is of particular interest for parenteral
      depot systems.

PMID- 9653635
TI  - [Max Weber's disease. Research on the disease and therapeutic management at the
      turn of the century].
AB  - This article on the German economist and sociologist Max Weber (1864-1920)
      continues our pathographic and psychohistoric studies on the interrelations
      between his life, his illness, and his work on "Protestantic Ethics and the
      Spirit of Capitalism". In a former paper (Frommer u. Frommer, 1993) we focussed
      on Weber's definition of modern society as an "iron cage" determined by Western
      rationalism. His theory, which shows that this cultural background demands a
      great amount of role conformity from the individual, converges with current
      psychopathological approaches on the personality of depressed patients. In the
      second article we report on results of our research on further personal
      documents, and some medical certificates by Weber's physicians. These documents
      demonstrate the diagnosis of a severe depression in a narcisstic and hypernomic
      personality.

PMID- 9653636
TI  - [Development of the AMDP module for identification of obsessive- compulsive
      symptoms. Conceptualization and empirical results].
AB  - Results of epidemiology and comorbidity studies have recently demonstrated the
      psychopathological relevance of obsessive-compulsive symptoms. Therefore the
      "Arbeitsgemeinschaft fur Methodik und Diagnostik in der Psychiatrie" (AMDP) has
      started to develop a rating scale for a quick and precise assessment of obsessive
      compulsive symptoms. The actual version of the scale comprises 20 items on the
      dimensions "description", "distress and impairment" and "emotion and cognition".
      The results of a first empirical study (n = 137, psychiatric in- and outpatients)
      demonstrated excellent internal consistency (Cronbach's alpha = 0.92), a split
      half reliability of 0.89 (Spearman-Brown), a test-retest reliability of r = 0.86
      and good convergent validity with the Yale-Brown Obsessive-Compulsive Scale (Y
      BOCS) and the Hamburger Zwangsinventar (HZI). The factor-analytical distribution
      of the 20 items revealed a 4-factor structure of the scale. The results are
      presented and their implications on further steps of the development of the scale
      are discussed.

PMID- 9653637
TI  - [Psychopharmacotherapy in pregnancy and breast feeding].
AB  - The primary purpose of this article is to review critically the literature on the
      use of psychotropic medications in pregnancy and during breast feeding in order
      to suggest strategies for the clinical management of these periods. Use of
      psychotropic medications during pregnancy may cause three complications: 1.
      teratogenicity, 2. perinatal syndromes (neonatal toxicity), and 3. postnatal
      behavioural sequelae (behavioural toxicity). The literature features few well
      controlled studies concerning these points, so that the available information
      allows only few conclusions. Exposure to certain psychotropic drugs in utero may
      increase the risk for some specific congenital anomalies; there is mostly no
      strong evidence for behavioural toxicity in children exposed to psychotropic
      medications. Use of psychotropic drugs during pregnancy and breast feeding may be
      appropriate in many clinical situations and should include thoughtful weighing of
      risk of pre- and postnatal exposure versus risk of relapse following drug
      discontinuation. The authors try to present disorder-based guidelines for
      psychotropic drug use during pregnancy and breast feeding and for psychiatrically
      ill women who wish to conceive.

PMID- 9653638
TI  - [Coping-oriented group therapy for patients with schizophrenic or schizoaffective
      disorders. An exploratory study].
AB  - The controlled study presented here was designed to examine the influence of the
      degree of structure of a coping-orientated therapy, the changes between the
      beginning and the end of therapy concerning satisfaction with therapy,
      psychopathology, attitude towards medication, coping behaviour and social
      variables, the effects on the days of hospitalisation within one year after the
      end of treatment and the relevant variables to predict the outcome twelve months
      later. It could be shown that patients in a relatively unstructured supportive
      group therapy wished to discuss topics that are very similar to those of coping
      orientated therapy, that coping-orientated therapy results especially in an
      increase in knowledge about illness and treatment and that the therapeutic
      outcome after a one-year period can best be predicted by the degree of active
      coping strategies, social adaptation, trust in medication and cognitive
      variables.

PMID- 9653639
TI  - [The clinical picture and stability of non-cognitive symptoms in patients with
      Alzheimer's disease].
AB  - The purpose of this study was to investigate noncognitive symptoms in Alzheimer's
      disease in order to identify symptom patterns and to study stability of such
      patterns prospectively. Furthermore, variables were examined which could be
      associated with certain types of symptom patterns or could be predictors of
      change of these patterns. Forty-eight patients with the clinical diagnosis of
      probable Alzheimer's disease were included in this study and were assessed weekly
      over a three-week period. Noncognitive symptoms were rated according to the
      Behavioral Abnormalities in Alzheimer's Disease Rating Scale (BEHAVE-AD) and the
      Dementia Mood Assessment Scale (DMAS) and to a set of items specifically
      assessing misidentifications. By means of principal component factor analysis
      different noncognitive symptom patterns were obtained yielding a four-factor
      solution. They were mapped as rational domains with respect to clinical
      experience: 'depression', 'apathy', 'psychotic symptoms/aggression',
      'misidentifications/agitation'. Demographic and clinical variables were not
      associated with the factor solutions and did not predict change of the factor
      values. The results demonstrate that in Alzheimer's disease there are distinct
      noncognitive symptom patterns with at least short-term prospective stability.
      None of the examined clinical variables, such as age at entry, the status of the
      patients (outpatient or inpatient) or dementia severity, exerted substantial
      influence on the noncognitive symptom patterns. Further investigations should
      concentrate on the pathological and prognostical correlates of noncognitive
      symptom patterns in Alzheimer's disease.

PMID- 9653640
TI  - A genome survey for novel Alzheimer disease risk loci: results at 10-cM
      resolution.
AB  - We completed a systematic survey of the human genome, conducted at an average
      resolution of 10 cM, for the identification of simple sequence tandem repeat
      polymorphisms (SSTRPs) that target new risk genes for Alzheimer disease (AD) by
      virtue of linkage disequilibrium. The efficiency of our association study was
      enhanced by genotyping pools of DNA from autopsy-confirmed cases with AD and
      matched controls. Allelic associations with AD were observed for 6 of the 391
      SSTRPs in the CHLC Human Screening Set/Weber Version 6 (Research Genetics, Inc.,
      Huntsville, AL): D1S518, D1S547, D10S1423, D12S1045, D19S178, and DXS1047. These
      allelic associations were replicated in an independent sample of autopsied AD
      cases and controls recruited from a geographically disparate site. The
      association of the large D19S178 alleles with AD appeared to arise from linkage
      disequilibrium with the APOE epsilon 4 allele, whose effect on increasing the
      risk of AD has been established. None of the remaining SSTRPs was in close
      proximity to loci previously reported to influence the risk of developing AD.
      Instead, they may identify five novel AD susceptibility loci.

PMID- 9653641
TI  - Molecular cloning of the human p120ctn catenin gene (CTNND1): expression of
      multiple alternatively spliced isoforms.
AB  - Catenins were discovered as proteins that are linked to the cytoplasmic domain of
      transmembrane cadherins. Among these junctional plaque proteins are several
      members of the Armadillo gene family: beta-catenin, plakoglobin, and p120ctn.
      Recently it became clear that some catenins also mediate nuclear signaling. We
      performed a detailed analysis of the human p120ctn gene (HGMW-approved symbol
      CTNND1) and its transcripts. The human p120ctn gene comprises 21 exons,
      potentially encoding up to 32 protein isoforms as products of alternative
      splicing. Human isoforms, designated 1 to 4, differ from each other by the start
      codon used. Additional isoforms are derived from combinations with alternatively
      used exons A (exon 18) and B (20), near the end of the open reading frame, and
      also with exon C (11) in the middle of the open reading frame. Hence, the longest
      isoform is of type 1ABC and comprises 968 amino acid residues. The functional
      consequence of the observed multitude of p120ctn splice variants awaits further
      study, but tissue-specific expression was obvious. Further, we demonstrate that
      the exon organization, which is not simply related to the Armadillo repeat
      structure, is very well conserved between the p120ctn gene and the related ARVCF
      gene, but not at all between these two genes and the beta-catenin or plakoglobin
      genes. The present data favor the concept that p120ctn is the prototype of a
      subfamily of Armadillo proteins, comprising ARVCF, p0071, delta-catenin/NPRAP,
      and plakophilins 1 and 2, that are more related to each other than to other
      Armadillo proteins.

PMID- 9653642
TI  - A transcriptional Map of the FMF region.
AB  - Familial Mediterranean fever (FMF) is a recessively inherited disorder
      characterized by attacks of fever and serositis, which affects primarily non
      Ashkenazi Jews, Armenians, Turks, and Arabs. We present here a transcriptional
      map covering the FMF locus that we constructed in the course of the positional
      cloning of the gene responsible for this disease. This map was established from a
      contig constructed with YAC, BAC, and cosmid clones and covers about 500 kb of
      16p13.3. It contains nine transcriptional units corresponding to known genes or
      to genes belonging to known gene families, 23 gene fragments characterized by
      partial sequences, and an endogenous retrovirus sequence. It thus considerably
      increases the number of genes in this interval and improves our knowledge
      concerning some of the genes or gene families present in this region. Data
      accumulated in this region were also used in a comparative study of different
      methods of exon detection.

PMID- 9653643
TI  - The complete mitochondrial DNA sequence of the rabbit, Oryctolagus cuniculus.
AB  - The nucleotide sequence of the complete mitochondrial DNA (mtDNA) molecule of the
      rabbit (Oryctolagus cuniculus, order Lagomorpha) was determined. The length of
      the molecule is 17,245 nt, but the length is not absolute due to the presence of
      different numbers of repeated motifs in the control region. The organization and
      gene contents of the mtDNA of the rabbit conform to those of other eutherian
      species. The putative secondary structures of the tRNAs of the rabbit have been
      described. These structures as well as the structure of the L-strand origin of
      replication comply with those characteristic for eutherians in general. The
      compositional differences between the two mtDNA strands have also been detailed.

PMID- 9653644
TI  - Cloning and mapping of human chromosome 6q26-q27 deleted in B-cell non-Hodgkin
      lymphoma and multiple tumor types.
AB  - Frequent deletions of the distal region on the long arm of chromosome 6 have been
      reported in multiple human tumors including B-cell non-Hodgkin lymphoma (B-NHL),
      suggesting the presence of one or more tumor suppressor genes (TSGs) at this
      locus. Previously, we identified a region of minimal molecular deletion at 6q25
      q27 (RMD-1) in B-NHL cases. To facilitate positional cloning efforts to identify
      the RMD-1 TSG(s), a yeast artificial chromosome (YAC) contig consisting of 110
      clones was constructed across 6q26-q27 by sequence-tagged site/probe content
      mapping. The contig integrates 79 ordered markers including restriction fragment
      length polymorphisms, minisatellites, microsatellites, YAC-insert termini,
      expressed sequence tags, and known genes. It spans 34 cM and has a minimal tiling
      path of approximately 12 clones, covering an estimated 9-14 Mb with nearly every
      marker on the map showing at least double linkage to its adjacent markers. Dual
      color fluorescence in situ hybridization of selected marker pairs on normal
      pachytene chromosome 6 further confirmed the YAC-based mappings. Utilizing a loss
      of constitutional heterozygosity assay in the B-NHL tumor panel, 24 additional
      6q26-q27 polymorphic markers (21 mapping to the contig) further defined RMD-1
      between markers D6S186 proximally and D6S227 distally. The minimal tiling path of
      the B-NHL RMD-1 consists of approximately 8 YAC clones, providing a size estimate
      of 5-9 Mb. This interval contains, in their entirety, several smaller candidate
      TSG critical regions previously delimited in other tumor systems. The AF-6 gene,
      mapping within RMD-1, revealed no mutations in a small subset of B-NHL. The
      deletion and physical maps presented herein provide a framework for the
      identification of the gene(s) involved in B-NHL as well as other malignancies and
      diseases mapped to this region and provide the initial reagents for large-scale
      genomic sequencing.

PMID- 9653645
TI  - Molecular cloning and expression analysis of five novel genes in chromosome 1p36.
AB  - The human chromosome 1p36 region displays frequent nonrandom chromosomal
      deletions and translocations in a number of human malignancies; these are thought
      to inactivate tumor suppressor genes. To identify these putative tumor
      suppressors we employed exon trapping, cDNA selection, and zoo blot analysis to
      clone five new genes located in 1p36. Two of these represent novel genes and were
      designated C1orf1 and xylan 1,4-beta-xylosidase 1 (XBX1). Two further genes
      represented new members of known gene families: PTPRZ2 was a tyrosine phosphatase
      and FRAP2 represented a FKBP12-rapamycin-associated protein. The fifth gene
      identified, ENO1L1, was significantly homologous to c-myc promoter binding
      protein, MBP-1, and to enolase 1 (ENO1). It colocalized with alpha enolase (ENO1)
      on a single P1 clone. ENO1L1 differed from both ENO1 and MBP-1 in the
      organization of its 5' untranslated sequences. Second, MBP-1 contained two single
      base insertions not present in either ENO1 or ENO1L1 sequences, which led to a
      shift in the MBP-1 reading frame. Expression analysis revealed two brain-specific
      transcripts of 7.9 and 6.5 kb for PTPRZ2. In contrast, C1orf1, FRAP2, ENO1L1, and
      XBX1 appeared to be expressed ubiquitously in the tissues tested, with transcript
      sizes of 4.5, 8.7, 1.75, and 4.5 kb, respectively. Using fluorescence in situ
      hybridization, we mapped the five novel genes relative to chromosome 1p36
      breakpoints present in three established tumor cell lines and one nontumor cell
      line. The karyotypic abnormalities in these cell lines were exploited as
      chromosomal landmarks; we could thus show that the telomere to centromere gene
      order was PTPRZ2-(MBP-1/ENO1/ENO1L1)-(C1orf1/XBX1)-+ ++FRAP2. The localization of
      these genes to a chromosomal region that is prone to deletions in human cancers
      makes them potential candidate tumor suppressors.

PMID- 9653646
TI  - Structure, organization, and chromosomal mapping of the gene encoding
      macrosialin, a macrophage-restricted protein.
AB  - Murine macrosialin and its human homologue CD68 are heavily glycosylated
      transmembrane proteins expressed specifically in macrophages and macrophage
      related cells. Macrosialin is predominantly a late endosomal protein but is also
      found on the cell surface where it binds oxidized LDL, an important factor in
      atherogenesis. We have cloned and sequenced the murine macrosialin gene (Cd68)
      and localized it by linkage analysis to chromosome 11. The gene is 1908
      nucleotides long from the start site of transcription to the end of the 3'UTR. It
      has six exons, which range in size from 79 to 434 nucleotides. The promoter lacks
      a classical TATA box but contains other protein binding sites consistent with
      preferential monocyte/macrophage gene expression. Although the function of
      macrosialin is unknown, it might play a role in lipoprotein regulation given its
      binding of oxidized LDL in vitro and its colocalization to a region on chromosome
      11 involved in the control of HDL levels.

PMID- 9653647
TI  - Structural organization and sequence of CLN2, the defective gene in classical
      late infantile neuronal ceroid lipofuscinosis.
AB  - Mutations in the CLN2 gene result in classical late infantile neuronal ceroid
      lipofuscinosis (LINCL), a fatal childhood neurodegenerative disease. In this
      report, we present the complete sequence of the human CLN2 gene and define its
      physical relationship with two other genes that have been previously mapped to
      chromosome 11p15. The CLN2 gene consists of 13 exons and 12 introns and spans
      6.65 kb. By S1 mapping and primer extension, the 5'-terminus of the CLN2 mRNA was
      mapped to 32 nucleotides upstream of the proposed initiation codon. A number of
      other elements were found to be located in close proximity to CLN2, including the
      gene encoding transcription factor TAFII30, the gene encoding intregrin-linked
      kinase, and an approximately 914-bp fragment that is 82% identical to
      antithrombin III. In addition, an EST cDNA clone that is transcribed on the
      strand opposite to CLN2 and that overlaps a portion of the CLN2 gene was
      identified. Finally, a set of primer pairs are presented for the amplification of
      the coding sequences, putative promoter, and splice junctions of the CLN2 gene.
      Taken together, this information will facilitate the molecular analysis of and
      genetic testing for classical LINCL.

PMID- 9653648
TI  - Cloning and characterization of ZNF189, a novel human Kruppel-like zinc finger
      gene localized to chromosome 9q22-q31.
AB  - A 3-kb-long cDNA encoding a Kruppel-like human zinc finger protein was isolated
      and mapped to chromosome 9q22-q31. The ZNF189 gene encodes a protein with 16 zinc
      fingers at its C-terminus and belongs to the Kruppel-associated box (KRAB)
      containing group of zinc finger proteins. Four differently spliced cDNA
      transcripts, differing at the 5' coding region where a KRAB A repressor domain is
      encoded, were isolated. In addition, Northern blot analysis indicates the
      presence of two additional unidentified splice variants. Comparison of cDNA and
      genomic sequences shows that the ZNF189 gene spans approximately 11 kb and is
      organized into at least four exons, the large 3'-end exon coding for the complete
      zinc finger domain and the 3' untranslated region. ZNF189 is expressed in all
      tissues and cell types currently investigated, at varying levels, but with a
      tissue- or cell-type-restricted expression pattern for the different splice
      variants. ZNF189 is conserved in the genome of several mammalian species. Direct
      sequencing of the ZNF189 gene in microdissected tumor biopsies of sporadic basal
      cell carcinoma and squamous cell carcinoma reveals no mutations in the coding
      sequence or at exon/intron boundaries.

PMID- 9653649
TI  - Identification and characterization of the gene encoding a second proteolipid
      subunit of human vacuolar H(+)-ATPase (ATP6F).
AB  - The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in
      H+ transport in microvesicles and other acidic organelles. We have cloned the
      second human proteolipid of the V-ATPase (designated hATP6F), a homologue of the
      Saccharomyces cerevisiae proteolipid VMA16, which is an essential subunit of
      yeast V-ATPase. hATP6F is a hydrophobic protein with five putative transmembrane
      segments, having 61% amino acid identity and 83% similarity to the yeast protein,
      except in the N-terminus, and contains a conserved glutamic acid residue (Glu98)
      that is essential for H(+)-transporting activity. The gene for hATP6F (gene
      symbol, ATP6F), which consists of eight exons and spans approximately 3.5 kb, was
      isolated and mapped to human chromosome band 1p32.3 and the region 10.81 cR
      centromeric of the STS marker SHGC36789 (LOD = 6.75) by fluorescence in situ
      hybridization and radiation hybrid mapping, respectively. This is the first
      evidence in human of the existence of a second gene encoding a distinct V-ATPase
      proteolipid.

PMID- 9653650
TI  - Long uninterrupted CGG repeats within the first exon of the human FMR1 gene are
      not intrinsically unstable in transgenic mice.
AB  - Despite the increasing number of disorders known to result from trinucleotide
      repeat amplification, the molecular mechanism underlying these dynamic mutations
      is still unknown. In an attempt to create a mouse model for the CGG repeat
      instability seen in Fragile X syndrome, we constructed transgenes corresponding
      to FMR1 premutation alleles. While in humans these alleles would expand to full
      mutation with almost 100% certainty upon maternal transmission, they remain
      stable in our transgenic mice. Therefore, the presence of a large number of
      uninterrupted CGGs is not sufficient to cause instability in mice, even in the
      context of flanking human FMR1 sequences.

PMID- 9653651
TI  - cDNA cloning and characterization of a human proteasomal modulator subunit, p27
      (PSMD9).
AB  - We have employed cDNA cloning to deduce the complete primary structure of a new
      subunit, designated p27, of the modulator trimer complex that stimulates the
      association of the PA700 regulator with the catalytic 20S proteasome to form the
      ATP-dependent active 26S proteasome. We found two distinct cDNAs encoding two
      highly homologous proteins except in the C-terminal region, which are termed
      tentatively p27-1 and p27-2. The short p27-2 cDNA has a deletion of 65 bp near
      the 3'-end region of the long p27-1 cDNA, which encodes a large protein with an
      extended C-terminal region, designated p27-L, whereas the long p27-1 cDNA encodes
      a small protein named p27-S. The polypeptides of p27-L and p27-S consist of 223
      and 209 amino acid residues with calculated molecular masses of 24,852 and 22,764
      and isoelectric points of 6.50 and 5.28, respectively. Immunoblot analysis with
      anti-p27 antibody revealed that p27, together with two other ATPase components,
      TBP1 and p42, was associated with not only the modulator complex but also
      significantly with the 26S proteasome complex, suggesting that the three are
      common/sharing subunits in these two complexes. By the fluorescence in situ
      hybridization method, the p27 (PSMD9) gene was mapped to the q24.2-q24.3 band of
      human chromosome 12. Computer-assisted homology analysis revealed the high
      sequence similarities of p27-L with a possible counterpart in Caenorhabditis
      elegans and Saccharomyces cerevisiae whose function is yet unknown, the yeast
      gene that is here termed NAS2 (non-ATPase subunit 2). Disruption of NAS2 had no
      effect on cell viability, indicating that the subunit is not essential for
      proliferation of yeast cells.

PMID- 9653652
TI  - A putative human zinc-finger gene (ZFPL1) on 11q13, highly conserved in the mouse
      and expressed in exocrine pancreas. The European Consortium on MEN 1.
AB  - In the process of identification of the multiple endocrine neoplasia type 1 gene,
      which was recently published, we isolated a novel gene in the 11q13 region. This
      gene (named ZFPL1, for zinc-finger protein-like 1) is expressed strongly in the
      exocrine pancreas as a 1.4-kb polyadenylated RNA encoding a putative protein of
      310 amino acids. A mouse EST contig predicts an equally sized murine protein with
      91% amino acid sequence identity to the human protein. No significant homology
      with known proteins could be found through database screening. However, zinc
      finger-like domains and leucine-zipper-like motifs in the predicted ZFPL1 protein
      were identified, suggesting the presence of DNA-binding and dimerization domains
      possibly involved in transcription regulation. This notion is supported by the
      presence of a putative bipartite nuclear localization signal. This paper presents
      the full-length cDNA sequence for this gene, its genomic structure and
      chromosomal orientation, and expression studies by Northern blot hybridization
      and RNA in situ hybridization.

PMID- 9653653
TI  - Fine genetic and comparative mapping of the deafness mutation Ames waltzer on
      mouse chromosome 10.
AB  - The Ames waltzer (av) mouse mutant is an autosomal recessive deafness mutation on
      mouse Chromosome 10. Previously, av had not been mapped relative to molecular
      markers. We have performed an intersubspecific backcross with Mus musculus
      castaneus and mapped microsatellite markers in this cross. Toothpick PCR on
      previously frozen tissue samples from offspring was used as an efficient strategy
      to screen a large number of animals quickly. In 1258 progeny tested we found
      three recombinants for each of the flanking markers D10Mit199 and D10Mit64. In
      addition, nine different genes (Ank3, Bcr, Gnaz, Tfam, Mif, Mmp11, Dcoh, Pyp, and
      Gstt2) were mapped and eliminated genetically as candidate genes for av. av had
      been discussed as a potential mouse model for the human deafness loci Usher
      syndrome type ID (USH1D) and DFNB12. Comparative mapping shows that av maps near
      an evolutionary break point and makes it unlikely that those loci are human
      homologues of av. A human homologue of av is predicted to lie either on 22q11.2
      or on 10q21. The orientation of conserved linkage groups between these two human
      chromosomal regions relative to mouse Chromosome 10 was determined.

PMID- 9653654
TI  - Cloning and characterization of the full-length cDNA and genomic sequences
      encoding murine acid ceramidase.
AB  - The full-length cDNA and genomic sequences encoding murine acid ceramidase (AC;
      E.C. 3.5.1.23) have been isolated and characterized. The 2176-bp cDNA was
      approximately 80% identical to the human cDNA (Koch et al., 1996) and predicted a
      394-amino-acid polypeptide that was approximately 90% identical to the human
      protein. A fluorescence-based assay system was developed to determine AC
      enzymatic activity, and transfection of COS-1 cells with the full-length mouse
      cDNA led to increased AC activity, demonstrating its functionality. The murine AC
      gene, which spanned approximately 38 kb, consisted of 14 exons separated by 13
      introns. The exons ranged in size from 46 to 1038 bp and were flanked by
      exon/intron junctions that adhered closely to known donor and acceptor splice
      site consensus sequences. Exon 1 encoded the putative translation start site and
      the signal peptide region, while exon 14 encoded the carboxy end of the AC
      polypeptide and all of the 3' untranslated region. Sequence analysis of a 497-bp
      region upstream from the first in-frame ATG revealed several features of a
      housekeeping promoter, as well as several tissue-specific and/or hormone
      inducible regulatory sites. Insertion of this sequence into a chloramphenicol
      acyltransferase (CAT) expression vector led an approximately fivefold increase in
      CAT activity after transfection into NIH3T3 cells. Northern blot analysis and
      enzymatic assays also were carried out on various murine tissues to examine AC
      expression. Of the tissues studied, the highest AC activity and mRNA levels were
      found in the kidney, followed by the brain; almost no AC activity or mRNA was
      found in the testis or skeletal muscle. These latter studies provided clear
      evidence that despite the housekeeping function of AC, its expression was tissue
      specific.

PMID- 9653655
TI  - Cloning, expression pattern, and chromosomal assignment to 16q23 of the human
      gamma-adaptin gene (ADTG).
AB  - Adaptins are important components of clathrin-coated vesicles transporting ligand
      receptor complexes from the plasma membrane or from the trans-Golgi network to
      lysosomes. Adaptins, together with medium and small subunits, form a
      heterotetrameric complex called an adaptor, whose role is to promote the
      formation of clathrin-coated pits and vesicles. We present the cloning and
      sequencing of the human gamma-adaptin cDNA (HGMW-approved symbol ADTG) consisting
      of 3723 bp with an open reading frame capable of encoding a protein of 825 amino
      acids, 98.9% identical to the mouse protein. Northern blot analysis of the mouse
      and human gamma-adaptin genes revealed a ubiquitous and abundant expression,
      except in human adult lung. Using a monochromosomal somatic cell hybrid panel and
      fluorescence in situ hybridization, we mapped this gene to human chromosome
      16q23, which is syntenic with mouse chromosome 8, band D. In addition, we
      localized genes for two other components of the AP-1 adaptor, i.e., the medium
      (AP47) and small (AP19) subunits, to chromosomes 19 and 7, respectively.
      Expression analysis of these genes in human tissues revealed ubiquitously
      expressed transcripts of approximately 2.5 and 1.5 kb, respectively.

PMID- 9653656
TI  - Cloning genes encoding receptors related to chemoattractant receptors.
AB  - We report the cloning of a novel human gene (GPR32) encoding a putative G-protein
      coupled receptor (GPCR) of 356 amino acids and a related pseudogene psi GPR32.
      The deduced amino acid sequence of GPR32 shares 35-39% identity with members of
      the chemoattractant receptor family. psi GPR32 shares 93% nucleotide identity
      with GPR32. We identified a mouse EST encoding a putative GPCR (GPR33) of 309
      amino acids. The deduced amino acid sequence of GPR33 shares 30-35% identity with
      members of the chemoattractant receptor family and 36% identity with the receptor
      encoded by GPR32. The human orthologue of GPR33 contains a single basepair
      substitution with respect to the mouse, resulting in the presence of an in-frame
      stop codon within the predicted second intracellular loop, demonstrating that it
      is a pseudogene. Through fluorescence in situ hybridization and physical mapping
      of YACs, both GPR32 and psi GPR32 were mapped to chromosomal 19, region q13.3,
      while psi GPR33 was mapped to chromosome 14q12.

PMID- 9653657
TI  - Mutant rescue by BAC clone injection in zebrafish.
AB  - Genes essential for vertebrate body plan specification, organ development, and
      organ function are likely to be shared between mammals and zebrafish, but only in
      zebrafish have large-scale, genome-wide mutagenesis screens been conducted to
      isolate embryonic lethal mutations. Discovering the roles played by these
      disrupted genes requires their molecular characterization, which would be
      facilitated by assaying large cloned genomic DNAs for their potential to rescue
      mutant phenotypes. Here we demonstrate that bacterial artificial chromosomes can
      rescue the phenotype of floating head (flh) mutants. Homozygous flh embryos lack
      a differentiated notochord and have a reduced, discontinuous floor plate. Mutant
      embryos injected with genomic clones containing the flh+ gene often had stretches
      of several to many notochord cells overlaid by a row of floor-plate cells. In
      contrast, control mutant embryos injected with artificial chromosomes lacking the
      flh+ gene failed to form notochord. We conclude that the injection of large
      insert genomic clones will speed the isolation of zebrafish genes disrupted by
      mutation and hence the identification of gene functions necessary for development
      of vertebrate embryos.

PMID- 9653659
TI  - Distribution of transcription factor binding sites in the yeast genome suggests
      abundance of coordinately regulated genes.

PMID- 9653658
TI  - A gene for recessive nonsyndromic sensorineural deafness (DFNB18) maps to the
      chromosomal region 11p14-p15.1 containing the Usher syndrome type 1C gene.
AB  - Autosomal recessive nonsyndromic sensorineural deafness segregating in a large
      consanguineous Indian family was mapped to chromosome 11p14-p15.1 defining a new
      locus, DFNB18. A maximum lod score of 4.4 at theta = 0 was obtained for the
      polymorphic micro-satellite marker D11S1888. Haplotype analysis localizes this
      gene between markers D11S1307 and D11S2368, which is approximately 1.6 cM and
      encompasses the region of Usher syndrome type 1C (USH1C). We postulate that
      DFNB18 and USH1C are allelic variants of the same gene.

PMID- 9653660
TI  - Mapping of two mouse membrane-type matrix metalloproteinase (MT-MMP) genes, Mmp15
      and Mmp16, to mouse chromosomes 8 and 4, respectively.

PMID- 9653661
TI  - B-cell activation in vitro by helper T cells specific to a protein region that is
      recognized both by T cells and by antibodies.
AB  - This laboratory had previously mapped the regions of T and B cell recognition on
      sperm whale myoglobin (Mb). Mb has five regions (E1-E5) that are recognized by
      both T cells and B cells (i.e. antibodies, Abs) and an additional region (E6)
      that is recognized exclusively by T cells (i.e., TE6) and to which no Abs are
      detectable. The responses to the site are each under separate genetic control.
      Recently, we showed in an H-2d haplotype that TE6 cells preferentially activated
      Mb-primed B cells (BMb) that made Abs against sites within E3 and E4 on the same
      protein. In the present work, we established, from Mb-primed SJL mice, an E4
      specific T cell line (TE4) by passage in vitro with synthetic peptide E4. At
      relatively low numbers, these T cells activated syngeneic BMb cells in vitro to
      produce anti-Mb Abs that recognized each of the antigenic sites within regions
      E1, E2, E3, E4 and E5. We confirmed the ability of TE4 to activate B cells that
      produce Abs against each of these regions by allowing TE4 to activate in vitro
      syngeneic B cells that had been primed with E1, E2, E3, E4 or E5. The helper
      activity of TE4 cells was dependent on the in vitro concentration of the
      challenge Ag (intact Mb or peptide E4). Thus, T cells against an epitope may
      provide help restricted to B cells that make Abs against selected antigenic sites
      or they may activate B cells that make Abs against all the antigenic sites of a
      protein. This might depend on the site-specificity of the T cell and/or on the
      host.

PMID- 9653662
TI  - Petechial hemorrhages in the small intestinal Peyer's patches: a new
      manifestation of systemic anaphylaxis.
AB  - Systemic anaphylaxis in the rat has major manifestations in the small intestine.
      In August rats, but not in other strains, intestinal anaphylaxis was accompanied
      by petechial hemorrhages in Peyer's patches. The occurrence of petechiae was not
      proportional to the intensity of prostration, cyanosis or gut congestion. No
      hemorrhages were found in other organs. The petechiae occurred in August rats of
      either sex after sensitization and challenge with any of several antigens and
      adjuvants and after passive sensitization with antiserum. The number of Peyer's
      patches with hemorrhage varied from one to all 20 in individual rats. The
      occurrence of petechiae was not influenced significantly by the route of
      sensitization or challenge, by the presence or absence of pinworms in the cecum,
      or by ancillary treatment at time of challenge with normal serum, normal blood,
      heparin, pertussis vaccine or lipopolysaccharide. The intestinal mast cells of
      the susceptible August rats were not different from the mast cells of the
      resistant strains. Furthermore, mast cells did not reside in the lymphoid
      follicles of Peyer's patches which was the site of the petechial hemorrhages in
      anaphylactic August rats. Nor did injections of histamine, serotonin or both
      cause hemorrhages in Peyer's patches.

PMID- 9653663
TI  - Two novel screening methods for selecting monoclonal antibodies which
      specifically inhibit DNase I enzyme activity.
AB  - Two novel screening methods, single radial enzyme diffusion and the DNA-cast
      polyacrylamide gel electrophoresis, for selecting monoclonal antibodies which
      detect human deoxyribonuclease I (DNase I) enzyme activity are described. The
      former was adopted for initial screening to select potential objective antibodies
      from numerous hybridoma culture supernatants, because it was easy to perform and
      a powerful mass-screening tool. The latter was utilized for the subsequent
      precise selection of the antibodies in the supernatants selected after
      preliminary screening by the former, because it was clearly more accurate and
      sensitive, although the procedure was slightly more complicated. The consecutive
      use of these two methods resulted in the isolation of 25 anti-human DNase I
      antibodies, all of which specifically inhibited the activity of human DNase I.

PMID- 9653664
TI  - Age-related changes in primary and secondary immune organs of the mouse.
AB  - The present work describes the murine immune tissue evolution with age with
      special emphasis on the bone marrow. To that effect we monitored the weights of
      the thymus, spleen and axillary lymph nodes over the first year of life in
      C57BL/6 male and female mice. In addition, we monitored the relative proportions
      of erythroid, lymphoid and myeloid cells in the bone marrow, and performed in
      vitro migration assays of bone marrow cells to thymic supernatants, with the aim
      of determining whether the migration of such cells or the thymic attractive
      capacity are affected by age. Before puberty, a remarkable decline in the
      relative weight of the thymus, spleen and lymph nodes was observed; after that
      stage, however, only the thymus showed an involution. The proportion of myeloid
      cells in the bone marrow showed an increase with age. Furthermore, the migration
      of myeloid cells to thymic supernatants increased with age and paralleled the
      time-course of the myeloid cell increase found in the bone marrow. More
      interestingly, the proportion of lymphoid cells to total bone marrow cells showed
      a clear decline with age. The time-course of this decline closely paralleled that
      of thymus weight, suggesting that the involution of the thymus may be related to
      changes in the cell composition of the bone marrow.

PMID- 9653665
TI  - Secretory component production by polarized epithelial cells from the human
      female reproductive tract.
AB  - At mucosal surfaces, the polymeric Ig receptor (pIgR) is responsible for
      transporting polymeric IgA across epithelial cells. The purpose of this study was
      to determine whether normal epithelial cells from the female reproductive tract
      form tight junctions and produce secretory component, the external domain of the
      pIgR. Uterine, cervical and vaginal tissues from women at different stages of the
      menstrual cycle and following menopause were used to prepare purified epithelial
      cell sheets, which were cultured in cell chambers. Transepithelial resistance was
      measured and the media from apical and basolateral compartments assayed for
      secretory component. Secretory component produced by uterine epithelial cells
      accumulated preferentially in apical compartment and correlated with increased
      transepithelial resistance. Seeding as epithelial sheets at 1 x 10(6) cells/cm2
      of matrix coated cell chambers was required for growth. Epithelial cells from
      endo-cervix and ecto-cervix, but not the vagina, also showed preferential
      production and release of secretory component into the apical chamber. In
      conclusion, normal epithelial cells from the human female reproductive tract grow
      to confluence, become polarized and produce secretory component. Our results
      suggest that uterine and cervical epithelial cells play a key regulatory role in
      the control of IgA transcytosis from tissue into secretions.

PMID- 9653666
TI  - Administration of silica sensitizes lipopolysaccharide responsiveness of murine
      macrophages but inhibits T and B cell priming by inhibition of antigen presenting
      function.
AB  - Macrophages play a key role in natural host defense against infection by a
      variety of pathogens. In addition, macrophages initiate the development of
      acquired immunity via antigen processing and presentation. The role of
      macrophages in resistance to pathogens, the development of autoimmune diseases
      and the induction of acquired immunity has been studied by treatment of rodents
      with reagents which are cytotoxic. We have studied the effects of one such
      reagent, silica, on the function of spleen macrophages and peritoneal exudate
      cells (PEC). Intraperitoneal administration of silica caused the accumulation of
      spleen macrophages and neutrophils, reduction in the number of B cells and had a
      modest effect on T cell abundance. The percentage of CD11b+ PEC was not affected
      by silica treatment but total PEC recovery was diminished 5-8 fold. Silica
      treatment did not cause release of TNF-alpha or IL-1-beta but, when stimulated
      with lipopolysaccharide (LPS) in vitro after silica treatment, PEC or spleen
      macrophages produced elevated levels of both cytokines compared to controls. In
      contrast, release of IL-12 from non-LPS treated PEC was stimulated 4-5 fold by
      silica treatment. In addition, sensitivity to LPS toxicity in vivo was
      significantly enhanced by silica. The ability of macrophages to present antigen
      to a T cell clone in vitro was found to be dramatically inhibited by silica
      treatment, as was the ability to prime antigen-specific T cells and B cells by
      antigen injection. Collectively these data demonstrate that silica treatment
      enhances macrophage sensitivity to LPS exposure but inhibits antigen processing
      and presentation.

PMID- 9653667
TI  - Stress, neuropsychiatric disorders and immunological effects exerted by
      benzodiazepines.
AB  - Psychoneuroimmunology is a growing scientific field which deals with the mutual
      interplay between nervous and immune systems. In this framework, many data have
      demonstrated that cytokines (CKs) derived from the periphery are able to cross
      the blood brain barrier and act upon the central nervous system (CNS) [e.g., the
      hypothalamic-pituitary-adrenal axis (HPAA)], thus regulating several
      physiological functions (thermoregulation, sleep, appetite) or damaging the
      nervous tissue, when released in exaggerated amounts. On the other hand, nervous
      cells, such as astrocytes and microglial cells also generate proinflammatory CKs
      which may be detrimental for the CNS. The neuromodulating CK network can be
      triggered by microorganisms and/or their products (i.e. bacterial endotoxins),
      but also stressful life events may activate the HPAA, thus affecting the immune
      system function. This review will place emphasis on some clinical conditions,
      such as phobia and migraine without aura (MWA), characterized by anxiety
      disorders. Patients affected by these neuropsychiatric alterations exhibit
      multiple functional deficits of phagocytes and T lymphocytes which allow
      penetration of various pathogens into the host. This is also supported by the
      detection of circulating bacterial endotoxins and the evidence of both
      spontaneous and induced exaggerated release of proinflammatory CKs in phobic and
      MWA patients. The possible iatrogenic effects of benzodiazepines (BDZ) on the
      immune system have been evaluated by in vitro and in vivo studies. In this
      respect, it emerges that diazepam exerts an inhibitory function on the immune
      system, while alprazolam behaves as an immunoenhancer. The presence of central
      and/or peripheral BDZ receptors on immune cells seems to be the key mechanism
      responsible for the immunomodulation exerted by these drugs.

PMID- 9653668
TI  - The plasma FK506-binding protein 12 level is related to acute cellular rejection
      in small bowel transplantation.
AB  - Since FK506 binding protein (FKBP12) inhibits dose-dependently the
      immunosuppressive activity of FK506 in vitro, plasma FKBP12 levels were measured
      after rat small bowel transplantation (SBTx). The mean plasma FKBP12 level in
      untreated recipients increased significantly at the onset of acute cellular
      rejection (ACR) compared to that in FK506-treated recipients without rejection at
      the same time after SBTx (P < 0.05). In both groups, however, the mean plasma
      FKBP12 level did not increase at 1 day after SBTx. These results suggest that
      plasma FKBP levels may be affected by ACR, but not by ischemia-reperfusion
      injury. Therefore, the plasma FKBP12 level should be considered as one of the
      parameters related to the immunosuppressive activity of FK506 in SBTx.

PMID- 9653669
TI  - Effect of endotoxin on cytokine production and cell dynamics in mice.
AB  - Previous studies have shown that endotoxin potentiates immune responses by direct
      stimulation of B cells and macrophages. In the present study, we assessed the
      ability of endotoxin to stimulate cells from different lymphoid tissue
      compartments to release cytokines. The in vitro stimulation of macrophages with
      endotoxin resulted in the production of IL-1 and TNF-alpha in a dose and time
      dependent manner. Endotoxin also induced the production of IL-2, IFN-gamma and IL
      4 secretion in a dose dependent manner in cultured spleen, mesenteric lymph nodes
      and Peyer's patches cells. The intraperitoneal administration of endotoxin in
      mice resulted in the accumulation of leucocytes in the peritoneal cavity and in
      the increase of IL-1, IL-6, TNF-alpha and IFN-gamma concentration in serum. In
      conclusion, this study confirmed that endotoxin possesses immunomodulatory
      activities capable of stimulating immune functions both in vitro and in vivo.

PMID- 9653670
TI  - In-line affinity chromatographic removal of specific antibody from rabbits with
      experimental myasthenia gravis as a prelude to immunotherapy.
AB  - Myasthenia gravis is an autoimmune disease in which antibodies are produced
      against one's acetylcholine receptors, resulting in complement-mediated membrane
      destruction and internalization of antibody-receptor complexes. Symptoms range
      from weakening of extraocular muscles to severe impairment of movement and
      breathing. Prior to administering a therapeutic agent to eliminate antibody
      producing lymphocytes, it will be necessary to remove specific antibody from the
      circulation. This process was investigated in an animal model of ex vivo specific
      immunoadsorption using awake, conscious rabbits. Following arterial blood
      separation, plasma was pumped upward through an affinity column containing
      covalently-bound acetylcholine receptor. Treated plasma was returned to the
      rabbit. Within a one-hour ex vivo procedure, specific antibody levels could be
      lowered from 16.2 ng/ml to less than 0.6 ng/ml, a reduction of more than 95%. By
      washing the column, at least four exchanges could be performed before specific
      antibody removal significantly diminished. The effects of specific antibody
      removal upon muscle function varied among individual rabbits, but if symptoms
      were not severe following passive transfer of purified monoclonal antibody to
      induce myasthenia, removal of 60% of the total specific antibody resulted in
      clinical improvement, as monitored by an animal's response to gallamine
      triethiodide.

PMID- 9653671
TI  - Modulation of cytoskeleton assembly capacity and oxidative response in aged
      neutrophils.
AB  - Several reports have emphasized that aged polymorphonuclear cells (PMN) exhibit
      an impairment of superoxide anion (O2-) generation when triggered with formyl
      methionyl-leucine-phenylalanine (FMLP) in comparison to the younger counterpart.
      Since microfilaments and microtubules are involved in PMN-mediated functions, in
      a group of old donors we assessed the effects of either actin stabilizing and
      disrupting agents, i.e. phalloidin and cytochalasin B, or microtubule
      stabilization or disruption by taxol and colchicine, respectively, on FMLP
      triggered neutrophil oxidative responsiveness. Results show that phalloidin
      treatment, at a concentration ranging from 10(-6) to 10(-8) M, gave rise to an
      inhibition of O2- release by aged PMN, while the same effect was seen in
      similarly treated young cells at a concentration of 10(-7) M only. On the
      contrary, cytochalasin B pretreatment led to an enhancement of O2- generation in
      both young and aged neutrophils, even if to a lower extent in the latter group.
      At the same time, taxol at 10(-8) M strength inhibited young cell responsiveness,
      while no effects were induced by colchicine treatment. Quite interestingly,
      elderly neutrophil function was negatively modulated by both microtubule
      affecting compounds. Altogether, these findings suggest the possible relevance of
      cytoskeletal affecting compounds in the modulation of FMLP-stimulated O2- release
      during senescence.

PMID- 9653672
TI  - In vivo anti-influenza virus activity of Kampo (Japanese herbal) medicine "sho
      seiryu-to"--stimulation of mucosal immune system and effect on allergic pulmonary
      inflammation model mice.
AB  - When BALB/c mice were treated with a Kampo (Japanese herbal) medicine "Sho-seiryu
      to (SST)" (1 g/kg, 10 times) orally from 7 days before to 5 days after the
      infection and infected with mouse-adapted influenza virus A/PR/8/34 by nasal-site
      restricted infection, SST caused increment of the influenza virus hemagglutinin
      specific IgA antibody secreting cells in nasal lymphocyte but not in Peyer's
      patch lymphocyte at 6 days after infection in comparison with water-treated mice.
      Oral administration of SST also augmented IL-2 receptor beta chain+ (activated) T
      cell in Peyer's patch lymphocyte, but not in the nasal lymphocyte. We previously
      reported that SST showed potent anti-influenza virus activity through
      augmentation of the antiviral IgA antibody titer in the nasal and broncho
      alveolar cavities of the mice (T. Nagai and H. Yamada, 1994, Int. J.
      Immunopharmacol. 16, 605-613). These results suggest that oral administration of
      SST shows anti-influenza virus activity in the nasal cavity by activation of T
      cell in Peyer's patch lymphocyte and stimulation of production of anti-influenza
      virus IgA antibody in nasal lymphocyte. When ovalbumin-sensitized allergic
      pulmonary inflammation model mice were administered orally with SST (1 g/kg) from
      8 days before (11 times) or from 2 h after (4 times) to 4 days after the
      infection and infected with mouse-adapted influenza virus A/PR/8/34, replications
      of the virus in the both nasal and broncho-alveolar cavities or only nasal cavity
      were significantly inhibited at 5 days after infection in comparison with water
      treated control by augmenting antiviral IgA antibody, respectively. These results
      suggest that SST is useful for both prophylaxis and treatment of influenza virus
      infection on patients with allergic pulmonary inflammation, such as bronchial
      asthma.

PMID- 9653673
TI  - Taraxacum officinale restores inhibition of nitric oxide production by cadmium in
      mouse peritoneal macrophages.
AB  - Nitric oxide (NO) produced at high concentrations by the inducible NO synthase is
      an important effector molecule involved in immune regulation and defense. The
      involvement of NO in the toxicity of cadmium (Cd) has been proposed. We have
      established that Cd inhibits the production of NO by recombinant IFN-gamma (rIFN
      gamma) and lipopolysaccharide-stimulated mouse peritoneal macrophages. In the
      present study, we searched restoration drug against the inhibition of NO
      production by Cd in Oriental medicine. An aqueous extract of Taraxacum officinale
      (Compositae) (TOAE) restored the inhibition of NO production by mouse peritoneal
      macrophages pretreated with Cd in a dose-dependent manner. The effect of TOAE was
      mainly dependent on TOAE-induced tumor necrosis factor-alpha (TNF-alpha)
      secretion. These results suggest that the capacity of TOAE to restore NO
      production from interferon-gamma (IFN-gamma)-primed mouse peritoneal macrophages
      is the result of TOAE-induced TNF-alpha secretion.

PMID- 9653674
TI  - Alterations in immune parameters associated with low level methylmercury exposure
      in mice.
AB  - Methylmercury (MeHg) is a known toxicant and continues to be a significant
      environmental contaminant. While the neurotoxicity and developmental toxicity of
      MeHg are well established, the immunotoxic effects of MeHg are just now being
      studied and described. This study evaluated strain and gender specific effects of
      low level, prolonged MeHg exposure in mice. Mice were exposed to MeHg in the
      drinking water (0, 3 or 10 ppm) for 4 weeks. Splenocytes and thymocytes were
      evaluated for alterations in immunophenotype, GSH levels, and intracellular Ca2+
      flux after mitogen stimulation. MeHg exposure resulted in alterations in
      splenocyte and thymocyte subsets and a dose dependent decrease in GSH levels (as
      measured by monochlorobimane fluorescence and flow cytometry) of all splenocyte
      subsets. This decrease in GSH was further confirmed by biochemical assay in
      splenocytes. In addition, there was a dose response related decrease in mitogen
      stimulated Ca2+ flux and in the percentages of CD4+ splenocytes and CD8+
      splenocytes from mice exposed to 10 ppm of MeHg. These results suggest that low
      level chronic MeHg exposure may cause immune disfunction by disturbing thiol
      redox balance, transmembrane signaling and splenic cellularity.

PMID- 9653675
TI  - Effects of low doses of oestradiol, testosterone and dihydrotestosterone on the
      immune response of broiler chicks.
AB  - Administration of either 1 microgram kg-1 BW oestradiol 17 beta (E2), 0.1 mg kg-1
      BW testosterone (T) or 0.2 mg kg-1 BW dihydrotestosterone (DHT) in feed to
      broiler chicks for 50 days caused increased serum concentration of the hormones
      compared to the control birds that were given no drugs. E2 and T but not DHT
      resulted in a significant decrease of the total number of leukocytes, lymphocytes
      and the weight of bursa of Fabricious. The hormones significantly reduced the
      macrophage phagocytic activity compared to controls. It is suggested that
      prolonged administration of low doses of E2 and T but not DHT to chicken may
      induce immunosuppressant effect.

PMID- 9653676
TI  - Diesel exhaust particles enhance airway responsiveness following allergen
      exposure in mice.
AB  - We have previously reported that intratracheal instillation of diesel exhaust
      particles (DEP) enhances allergen-induced eosinophilic airway inflammation, local
      expression of interleukin-5 and granulocyte macrophage-colony stimulating factor,
      and allergen-specific production of IgE and IgG in mice. The present study was
      undertaken to elucidate the effects of DEP on airway hyperresponsiveness as
      another characteristic feature of allergic asthma. The animals were randomized
      into four experimental groups that received intratracheal instillation with
      vehicle, ovalbumin (OVA), DEP, or the combination of OVA and DEP on a weekly
      basis for 6 weeks. Respiratory resistance (Rrs) was measured 24 h after the last
      instillation. An increase in Rrs in animals that inhaled acetylcholine was
      significantly greater in the combined treatment with OVA and DEP than in the
      other treatments. The present study indicates that DEP can enhance airway
      responsiveness associated with allergen exposure, and provides experimental
      evidence that DEP may deteriorate the pathophysiology of allergen-related
      respiratory disease such as allergic asthma.

PMID- 9653677
TI  - The utility of the Fear Survey Schedule-III: an extended replication.
AB  - This investigation examined the factor structure of the Fear Survey Schedule-III
      in patients with specific anxiety disorders, including patients with panic
      disorder, agoraphobia without panic, generalized anxiety disorder, social phobia,
      specific phobia, obsessive compulsive disorder, post traumatic stress disorder,
      and anxiety disorder NOS. Four factors were obtained, reflecting a similar
      structure as has been noted in other studies. However, the ability of the
      obtained factors to discriminate among patients with panic disorder, social
      phobia, and specific phobia was not high. Future directions are highlighted.

PMID- 9653678
TI  - Social anxiety and peer relations among adolescents: testing a psychobiological
      model.
AB  - This study tested hypotheses derived from Trower and Gilbert's (1989) model of
      social anxiety. Participants were 1,179 students (594 males and 585 females) in
      grades 6, 7, 8, 9, and 11. Participants completed the Social Anxiety Scale for
      Adolescents and a sociometric nomination task. Nominations from the following
      behavioral descriptors: most cooperative, class leader, fights the most, and
      easiest to push around, were used to classify students into four peer nomination
      groups (i.e., cooperative, friendly dominant, hostile dominant, and submissive).
      Results indicated that students classified as submissive reported greater social
      anxiety than those classified as cooperative, friendly dominant, and hostile
      dominant. Implications of these results for further study of the Trower and
      Gilbert (1989) model of social anxiety are discussed.

PMID- 9653679
TI  - Crime-related trauma: psychological distress in victims of bankrobbery.
AB  - This study examines the relationship between the experience of a traumatic event,
      that is, a bankrobbery, and its psychological consequences. Two groups of
      employees of a major commercial bank in the Netherlands participated in this
      study. One group (n = 310) consisted of subjects who had experienced a
      bankrobbery and worked in high-frequency bankrobbery areas; the other matched
      control group (n = 214) consisted of nonrobbed employees from banks in the same
      area. Victimized subjects displayed more signs of psychological distress than the
      control subjects, but distress decreased over time. The main findings of this
      study are that a depressive/avoidant coping style, strong threat perception
      during the robbery, and additional life events were positively related to
      posttraumatic distress as assessed by the Impact of Event Scale and the Symptom
      Check List (SCL-90), and self-esteem was negatively associated with the SCL-90
      only.

PMID- 9653680
TI  - An investigation of gender differences in social phobia.
AB  - The present study was an exploratory investigation of gender differences in a
      large sample of persons with social phobia. Potential differences in demographic
      characteristics, comorbidity, severity of fear, and situations feared were
      examined. No differences were found on history of social phobia, social phobia
      subtype, or comorbidity of additional anxiety disorders, mood disorders, or
      avoidant personality disorder. However, women exhibited more severe social fears
      as indexed by several assessment instruments. Some differences between men and
      women also emerged in their report of severity of fear in specific situations.
      Women reported significantly greater fear than men while talking to authority,
      acting/performing/giving a talk in front of an audience, working while being
      observed, entering a room when others are already seated, being the center of
      attention, speaking up at a meeting, expressing disagreement or disapproval to
      people they do not know very well, giving a report to a group, and giving a
      party. Men reported significantly more fear than women regarding urinating in
      public bathrooms and returning goods to a store. Additionally, there were some
      differences in the proportion of men and women reporting fear in different
      situations. Specifically, more women than men reported fear of going to a party,
      and more men than women reported fear of urinating in a public restroom. Gender
      differences among patients with social phobia are discussed in the context of
      traditional sex-role expectations.

PMID- 9653681
TI  - Additional findings on the association between anxiety sensitivity and
      hypochondriacal concerns: examination of patients with major depression.
AB  - Hypochondriacal concerns ranging from disease phobias to bodily preoccupations
      are common among patients with panic disorder. In a previous study of patients
      with panic disorder, we found that, of a number of symptom dimensions examined,
      anxiety sensitivity was the strongest predictor of hypochondriacal concerns. This
      finding has been the topic of subsequent debate in the anxiety literature, with
      concerns raised whether true hypochondriacal concerns were confounded with
      typical panic-related concerns. To clarify this issue, we now report on the
      association between anxiety sensitivity and hypochondriacal concerns in 100
      patients with major depression and no history of panic disorder. Consistent with
      our previous study, we found that of the symptoms examined--anxiety sensitivity,
      depressed mood, anxious mood, somatic symptoms, and anger/hostility--anxiety
      sensitivity was the strongest predictor of hypochondriacal concerns. Findings are
      discussed in relation to the role of catastrophic interpretations of somatic
      symptoms in depression, panic disorder, and hypochondriasis.

PMID- 9653682
TI  - Stressful life events and personality styles: relation to impairment and
      treatment outcome in patients with social phobia.
AB  - Forty-five patients with social phobia and 15 individuals with no mental disorder
      were compared on number and type of life events experienced. Social phobia
      patients were further examined to evaluate the effect of negative life events and
      of the interaction between personality style and life events on severity of
      impairment and reactions to cognitive-behavioral group therapy. Patients with
      social phobia reported more negative life events than participants with no mental
      disorder. Among patients with social phobia, more frequent negative life events
      were associated with higher scores on measures of depression and general anxiety.
      Patients high on autonomy who reported more negative autonomous (i.e.,
      achievement-oriented) life events also scored higher on measures of social
      anxiety and general anxiety. There were no significant interactions between
      sociotropy and the frequency of reported socially oriented negative life events.
      However, patients high on sociotropy scored higher on measures of social anxiety,
      depression, and general anxiety. Patients who had experienced more negative life
      events improved more after treatment on measures of social anxiety than did those
      who had experienced fewer negative life events. Implications of these findings
      and recommendations for future research are discussed.

PMID- 9653683
TI  - Worry themes in primary GAD, secondary GAD, and other anxiety disorders.
AB  - This study examines worry themes among 87 anxiety disorder patients divided into
      three groups: (a) 24 primary generalized anxiety disorder (GAD) patients, (b) 25
      secondary GAD patients, and (c) 38 other anxiety disorder patients (primarily
      obsessive-compulsive disorder, social phobia and panic disorder with
      agoraphobia). Structured and free-recall measures were used to measure five worry
      themes: relationships, work, finances, physical threat, and the future. Both
      types of measures revealed that GAD patients worry more about the future than non
      GAD patients. Further, post hoc analyses testing for linear relationships
      indicated that primary GAD patients worry more about the future than secondary
      GAD patients who in turn worry more about the future than other anxiety disorder
      patients. The results suggest that although worry about immediate problems may
      not differentiate GAD patients from other anxiety disorder patients, high levels
      of worry about future events may be a distinguishing feature of GAD.

PMID- 9653684
TI  - Why do episodes of panic stop?
AB  - Episodes of panic are self-limiting--they all come to an end. However, it has not
      been explained how and why they end. Neither the cognitive nor the biological
      theory of panic deals with this phenomenon. As a first step toward an
      understanding of what stops a panic, we collected evidence about the self
      limiting nature of these episodes. A semistructured interview was developed and
      conducted with 25 participants who had received a diagnosis of panic disorder.
      Participants reported a variety of triggers of panic, signs that a panic was
      ending, and strategies used to terminate panic episodes. A substantial proportion
      of participants indicated that there was a refractory period following panic
      episodes. The theoretical and therapeutic significance of this self-limiting
      feature of panic episodes is considered, as is the probable occurrence of a
      postpanic refractory period.

PMID- 9653685
TI  - The effect of joint mobilization as a component of comprehensive treatment for
      primary shoulder impingement syndrome.
AB  - Primary shoulder impingement syndrome is a common shoulder problem which, if
      treated ineffectively, can lead to more serious pathology and expensive
      treatment. This study examined whether subjects receiving joint mobilization and
      comprehensive treatment (hot packs, active range of motion, physiologic
      stretching, muscle strengthening, soft tissue mobilization, and patient
      education) would have improved pain, mobility, and function compared with similar
      patients receiving comprehensive treatment alone. Subjects were eight men and six
      women (mean age = 52.9 years) with primary shoulder impingement syndrome
      (superolateral shoulder pain, decreased active humeral elevation, limited
      overhead function). Following random assignment to experimental (N = 7) and
      control groups (N = 7), three blinded evaluators tested 24-hour pain (visual
      analog scale), pain with subacromial compression test (visual analog scale),
      active range of motion (goniometry), and function (reaching forward, behind the
      head, and across the body in an overhead position) before and after nine
      treatments. One-tailed analyses of covariance (baseline values as covariates)
      showed that the experimental group had less 24-hour pain and pain with
      subacromial compression test but no differences in range of motion and function
      (Mann-Whitney U) compared with controls. The experimental group improved on all
      variables, while the control group improved only on mobility and function (one
      tailed, paired t tests; Wilcoxon matched pairs). Age, side of dominance, duration
      of symptoms, treatment attendance, exercise quality, and adherence had no effect
      on the outcomes. Results may be affected by inadequate sample size, minimal
      capsular tightness, insensitive functional scale, nonspecific motion
      measurements, position at which mobilization treatment was given, or a strong
      effect of comprehensive treatment. Mobilization decreased 24-hour pain and pain
      with subacromial compression test in patients with primary shoulder impingement
      syndrome, but larger replication studies are needed to assess more clearly
      mobilization's influence on motion and function.

PMID- 9653686
TI  - Comparison of 6- and 7-day physical therapy coverage on length of stay and
      discharge outcome for individuals with total hip and knee arthroplasty.
AB  - Providing physical therapy service on Sundays is a much debated topic among
      hospital administrators. The purpose of this study was to determine if 7 days per
      week of physical therapy coverage results in shorter lengths of stay and
      differing discharge status than 6 days per week. A total of 140 subjects with hip
      or knee arthroplasty participated; there were 80 in the 6-day groups and 60 in
      the 7-day groups. Data on postoperative length of stay, discharge destination,
      and discharge disposition were collected by retrospective medical record review.
      The Mann-Whitney U test was used to test for differences in length of stay data,
      and the chi-squared test was used to test for differences in discharge
      disposition and discharge destination. No significant differences in
      postoperative length of stay, discharge destination, nor discharge disposition
      existed between the 6- and 7-day physical therapy coverage hip or knee
      arthroplasty groups. However, the power of the statistical tests applied was low.
      This study provides no evidence that 7-day per week physical therapy results in
      shortened postoperative length of stay, differing discharge destination, nor
      differing discharge disposition for patients undergoing hip or knee arthroplasty.

PMID- 9653687
TI  - The relationship between isokinetic quadriceps strength test and hop tests for
      distance and one-legged vertical jump test following anterior cruciate ligament
      reconstruction.
AB  - Isokinetic measurements and functional tests are often used to assess function
      following knee ligament reconstruction using the opposite limb as a control.
      However, the question of whether the uninvolved leg may serve as a reference on
      functional tests has not been adequately answered. In particular, the one-legged
      rebound vertical jump has not been used to assess functional levels following
      surgery of the cruciate ligament. The purposes of this study were: 1) to
      determine whether the uninvolved leg is within normal range of an age- and weight
      matched group, 2) to determine differences between the involved and uninvolved
      leg in patients after anterior cruciate ligament reconstruction, 3) to examine
      the relationship between knee extensor strength and four functional performance
      tests, and 4) to determine if the one-legged rebound vertical jump yields more
      information in the assessment of knee function than the other functional tests
      with respect to two time-frames. Fifty healthy subjects (group A, mean age = 28.1
      years) and 55 anterior cruciate ligament patients (groups B and C) participated
      in dynamometric measurement, one-legged and two-legged vertical jump, and the
      single- and the triple-hop test. Mean time for testing was 13 weeks following
      surgery for group B (N = 30, mean age = 27.8 years) and 54 weeks following
      surgery for group C (N = 25, mean age = 29.9 years). Pearson product moment
      correlation coefficients between peak torque and single and triple hop were r =
      .45, r = .48, r = .51, and r = .55 for groups B and C, respectively. Pearson
      product moment correlation coefficients between peak torque and the height of the
      vertical jump was r = .51 for group C. Results for group A revealed limb symmetry
      indices of 95% or more on all functional performance and isokinetic tests. In
      group B, all patients showed a limb symmetry index of less than 85% on all tests.
      In group C, the index for the vertical jump was the only functional test that
      fell below the level of 85%. Regardless of whether the dominant or nondominant
      leg is involved, the uninvolved leg can be used adequately as a reference guide
      for outcome from rehabilitation using these measurements. The one-legged vertical
      jump test is capable of detecting functional limitations of the lower limb
      following knee ligament reconstruction up to 54 weeks postoperatively.

PMID- 9653688
TI  - Knee joint accessory motion following anterior cruciate ligament allograft
      reconstruction: a preliminary report.
AB  - Early in the postoperative period, changes in tibial translation have been noted
      in patient populations following anterior cruciate ligament reconstructive
      surgery. Deformation due to a lengthening of the ligament graft has been the most
      widely accepted reason for the change in tibial translation. Treatment techniques
      have not been proven successful in the abatement or reversal of this graft
      lengthening. The purpose of this study was to investigate the effect of
      functional bracing on tibial translation during the first year postoperatively in
      a group of patients with early changes in tibial translation. Three consecutive
      patients with early increases in KT-2000 manual maximum total drawer following
      bone-patellar tendon-bone allograft reconstruction were identified as subjects in
      the control group. Five consecutive anterior cruciate ligament bone-patellar
      tendon-bone allografts with early increases in KT-2000 manual maximum total
      drawer were identified as subjects in the treatment group. These patients were
      followed monthly during the first year postoperatively by manual maximum total
      drawer KT-2000 testing. Criteria for inclusion in the treatment and control
      groups included KT-2000 testing, with an increase in translation of greater than
      or equal to 2 mm when compared with the uninvolved knee during the first year
      postoperatively. The treatment group was required to wear a functional knee brace
      during all weight-bearing activities until KT-2000 displacement measures were
      stabilized for 3 consecutive months. Treatment with the functional brace resulted
      in a mean 2.3-mm decrease in tibial translation in the manual maximum total
      drawer KT-2000 when comparing the involved and uninvolved knee prebracing with
      posttreatment. All five subjects in the treatment group had a decrease in tibial
      translation. A Median Test comparing the control and treatment group's KT-2000
      scores was significant at the p < .05 level. Patients who experience early
      increases in tibial translation with anterior cruciate ligament reconstructions
      may be assisted in a reduction of the displacement by the use of a functional
      brace.

PMID- 9653689
TI  - Quantification of elastic resistance knee rehabilitation exercises.
AB  - Elastic resistance exercises are frequently used for knee rehabilitation
      following injury and/or surgery. The evidence supporting this mode of
      rehabilitation is primarily anecdotal, and no biomechanical assessment of elastic
      resistance exercises has been previously published. The purpose of this project
      was to quantify muscle activation levels, knee joint angles, and applied force
      during five rehabilitation exercises utilizing an elastic resistance device.
      Twelve subjects with no previous knee injury performed double knee dip, hamstring
      pull, leg press, single knee dip, and side-to-side jump exercises while sagittal
      plane kinematics, applied force from the elastic resistance device, and
      electromyographic activity of eight lower extremity muscles were collected. The
      muscle activation patterns suggest a progressive continuum of rehabilitation
      exercises that can be applied to nonoperative injuries as well as anterior
      cruciate ligament reconstructions.

PMID- 9653691
TI  - Treatment of sexually transmitted diseases. 1998 recommendations by the Centers
      for Disease Control and Prevention.

PMID- 9653690
TI  - Hip biomechanics during gait.
AB  - The literature is devoid of complete descriptions of hip biomechanics during
      gait. We present for the first time simultaneously acquired in vivo acetabular
      contact pressures, ground reaction forces, kinematics, hip torques, and
      electromyographic (EMG) activity during gait with and without a cane from an 85
      year-old male with a left instrumented femoral head prosthesis. Highest
      acetabular contact pressures occurred in all gait trials at the posterosuperior
      acetabulum, just prior to peak EMG, adductor torque, and ground reaction force
      during late stance phase. Contralateral cane use reduced both peak acetabular
      contact pressure and gluteus medius EMG but not adductor torque or ground
      reaction force. These data identify a small area of high acetabular and femoral
      head stress that could occur during each of a human's millions of gait cycles
      annually and indicate that muscle activity, rather than solely body weight,
      drives hip loading, Clinicians who desire to limit hip loads should reduce both
      hip muscle contraction and weight bearing in late stance.

PMID- 9653692
TI  - Genuine stress urinary incontinence in women. New laparoscopic paravaginal
      reconstruction.
AB  - OBJECTIVE: To assess a new laparoscopic technique of paravaginal repair, adapted
      from a classic laparotomy procedure, for genuine stress urinary incontinence.
      STUDY DESIGN: From January 1992 to July 1997, 28 patients in a consecutive,
      prospective clinical case study were subjected to laparoscopic paravaginal
      repair. No concomitant surgery was performed. A clinical diagnosis of genuine
      stress urinary incontinence was documented by cystometry following a positive
      cough stress test. When indicated, a multichannel urodynamics study was
      performed. RESULTS: In 16 patients (57%) of 28, the right pelvic side was
      affected, and in 43% fascia damage was identified and repaired bilaterally. The
      average operative time was 2 hours, 45 minutes; average blood loss was 1.2 g
      hemoglobin. No intraoperative, immediate postoperative, delayed postoperative or
      anesthesia-associated complications were observed. Patients were discharged from
      the surgical units in an average of 5 hours, 15 minutes. There was no
      postoperative hospital readmission. CONCLUSION: Laparoscopic paravaginal repair
      is simple and safe and has a 93% cure rate. It is an attractive alternative to
      laparotomy.

PMID- 9653693
TI  - Myomectomy performed concurrently with tuboplasty.
AB  - OBJECTIVE: To determine whether women who require tuboplasty for infertility and
      have associated uterine leiomyomas that require removal should have the
      myomectomy done concurrently. STUDY DESIGN: Eighty-nine infertility patients
      underwent tuboplasty alone for proximal tubal obstruction, 30 others were treated
      by both myomectomy and tuboplasty during the same operation, and 15 others
      underwent tuboplasty, leaving the myomas in situ. The tuboplasty in all cases
      consisted of tubal resection and anastomosis (TRA). The pregnancy rates and
      outcomes in the three groups were compared. RESULTS: Of the 89 patients who
      underwent TRA alone, 74.2% (66 patients) became pregnant, and of those 66, 15.2%
      had a spontaneous miscarriage, 24.2% developed an ectopic pregnancy, and 60.6%
      achieved a viable birth. By comparison, of 30 patients who had both TRA and
      myomectomy, 63.6% (19 patients) conceived, and of those 19, 15.8% miscarried,
      26.3% developed ectopic pregnancies, and 57.9% achieved viable births. Of 15
      patients who underwent TRA leaving the myomas in situ, 73% (11) became pregnant,
      and of those 11, 45% (5) miscarried, 18% (2) had ectopic pregnancies and 36% (4)
      gave birth to viable infants. The incidence of pregnancies, ectopic gestations,
      miscarriages and viable births in the three groups showed no statistical
      differences. CONCLUSION: When myomectomy is indicated, because of the lack of
      disadvantages of performing it at the time of tuboplasty, the combined surgical
      approach should be the procedure of choice rather than leaving the myomas in situ
      for their removal in a separate operation at a later date.

PMID- 9653694
TI  - Fascia lata suburethral sling vs. Burch retropubic urethropexy. A comparison of
      morbidity.
AB  - OBJECTIVE: To compare morbidity from the fascia lata sling to that from the Burch
      procedure. STUDY DESIGN: The charts of 64 consecutive patients undergoing the two
      procedures were reviewed for perioperative, immediate postoperative and delayed
      postoperative complications. RESULTS: Mean age was significantly older and prior
      surgery more common in the sling group, but parity and weight were comparable for
      the two groups. Operative time, estimated blood loss, change in hematocrit,
      incidence of transfusion, use of narcotics and hospital stay were not
      statistically different. Duration of catheter use was 2.2 days longer in the
      sling group (8.96 vs. 6.75 days, P = .387). Comparison of the sling vs. Burch,
      respectively, showed persistent urge incontinence in 42.8% and 40.0%, new urge
      incontinence in 22.2% and 16.6%, and cystotomy in 11% and 0%. CONCLUSION: The
      fascia lata sling procedure has morbidity comparable to that of Burch retropubic
      urethropexy. Urge incontinence needs to be specifically addressed preoperatively
      in both groups of patients.

PMID- 9653695
TI  - Creighton Model NaProEducation Technology for avoiding pregnancy. Use
      effectiveness.
AB  - OBJECTIVE: To evaluate the use effectiveness of Creighton Model (CrM)
      NaProEducation Technology for avoiding pregnancy. STUDY DESIGN: CrM is a medical
      model of natural procreation education that is a fully standardized modification
      of the Billings ovulation method. This system has been used as a means to avoid
      pregnancy and has been prospectively evaluated in five use effectiveness studies.
      A prospective life-table analysis of the five studies (meta-analysis) was
      undertaken, yielding both net and gross rates. Discontinuation rates were also
      calculated. These studies were conducted at CrM centers in Omaha, St. Louis,
      Wichita, Houston, and Milwaukee. RESULTS: A total of 1,876 couples used CrM NET
      for a total of 17,130.0 couple months of use. The method and use effectiveness
      rates for avoiding pregnancy were 99.5 and 96.8 at the 12th ordinal month and
      99.5 and 96.4 at the 18th ordinal month, respectively. The discontinuation rate
      was 11.3% at the 12th ordinal month and 12.1% at the 18th ordinal month.
      CONCLUSION: CrM is highly effective as a means of avoiding pregnancy in both its
      method and use effectiveness. The method effectiveness has remained stable over
      the years of the studies, but the use effectiveness for avoiding pregnancy
      appears to have improved over the study period.

PMID- 9653696
TI  - Sperm penetration assay in predicting successful in vitro fertilization. A meta
      analysis.
AB  - OBJECTIVE: To determine if the performance of the sperm penetration assay (SPA)
      is useful in predicting successful in vitro fertilization (IVF). METHODS: A meta
      analysis was set up to determine the performance of SPA in the prediction of IVF
      success. We collected data on 647 patients in 24 studies. For each study, a two
      by-two table was constructed from the results of SPA and IVF. RESULTS: The
      sensitivity and specificity of SPA as compared to IVF were heterogeneous. A
      summary receiver operating characteristics curve could be estimated, showing that
      the sensitivity of SPA was only 37%, with a specificity of 95%. Subgroup analysis
      did not explain the lack of homogeneity. CONCLUSION: Since withholding IVF
      inappropriately has major consequences, performing SPA is insufficient for
      selecting patients for treatment with IVF-embryo transfer.

PMID- 9653697
TI  - Single-dose azithromycin for Chlamydia in pregnant women.
AB  - OBJECTIVE: To assess the efficacy and occurrence of severe side effects
      associated with the use of a single dose of azithromycin in the treatment of
      Chlamydia trachomatis in pregnant women. STUDY DESIGN: Patients and their sexual
      partners were randomized into three treatment groups: both the patient and her
      sexual partner received a single dose of azithromycin (group 1); the patient was
      given a standard course of erythromycin, while her partner was given a standard
      course of tetracycline (group 2); and the patient was given a single dose of
      azithromycin with the sexual partner given a standard course of tetracycline
      (group 3). Group 3 was included in order to assess the relative efficacy of
      tetracycline with respect to the use of azithromycin among patients and to
      indirectly assess possible patient reinfection by sexual partners. RESULTS: With
      respect to the cure rate, 4.5% of study participants given azithromycin has
      positive cultures vs. 21.1% of patients given erythromycin or tetracycline (P =
      .018). With respect to side effects severe enough to warrant a change in
      medication, 7.4% of patients receiving azithromycin reported suffering such side
      effects vs. 38.8% of patients given erythromycin (P = .02). Among sexual
      partners, 28.6% given tetracycline reported severe side effects vs. none of those
      given azithromycin (P = .03). CONCLUSION: Azithromycin in the treatment of C
      trachomatis in pregnant women substantially improved the cure rates while
      substantially reducing the occurrence of severe side effects associated with the
      use of a standard course of erythromycin. Since both tetracycline and
      erythromycin are known to be effective against C trachomatis infection, the
      improved efficacy of azithromycin is probably due to noncompliance with the
      multidose, multiday regimen associated with the use of these two antibiotics.

PMID- 9653698
TI  - Ectopic pregnancy in sterilized and nonsterilized women. A comparison.
AB  - OBJECTIVE: To assess whether differences occurred in the presentation, treatment
      and postoperative outcomes of ectopic pregnancy in sterilized and nonsterilized
      women. STUDY DESIGN: All cases of ectopic pregnancy admitted over five years at
      two hospitals were reviewed. Using a case-control method, patients with ectopic
      pregnancy and prior tubal sterilization were compared with the next nonsterilized
      patient with ectopic pregnancy admitted within 30 days. Statistical comparison,
      utilizing t tests, chi 2 tests of Fisher's exact test, when appropriate, was
      performed. RESULTS: Thirty-eight (18%) of 208 patients with ectopics during the
      study period had undergone prior sterilization. This group, when compared with
      the 38 nonsterilized patients with ectopics, was similar for gestational age at
      diagnosis, frequency of pelvic inflammatory and sexually transmitted diseases,
      and mean human chorionic gonadotropin (hCG) level; the preoperative sonographic
      findings were also similar in the two groups. Sterilized patients were less
      likely than controls to have had serial hCG levels, while their mean duration of
      symptoms at admission was shorter. Although both groups had a similar
      distribution of surgical management (laparoscopy, laparotomy or both) and
      postoperative complications, there were trends toward a higher risk of ectopic
      rupture and hemoperitoneum in sterilized patients. CONCLUSION: Ectopic
      pregnancies following tubal sterilization have clinical manifestations and
      surgical outcomes similar to those occurring without prior sterilization, except
      for less frequent determination of serial hCGs, probably related to a shorter
      duration of reported preceding symptoms. The trend toward more frequent rupture
      and hemoperitoneum in this group suggests that sterilized patients are less
      likely to heed the early warnings of this complication.

PMID- 9653699
TI  - Fetal congenital malformations. Biophysical profile evaluation.
AB  - OBJECTIVE: To study the association between various fetal congenital
      malformations and the biophysical profile (BPP), we tested the following
      hypotheses: (1) a specific organ system malformation is associated with the
      absence of one or more BPP parameters, and (2) four BPP parameters are not
      affected by the advancement of fetal maturation. STUDY DESIGN: From 1985 to 1995,
      316 fetuses with congenital malformations and 351 controls were identified in a
      high-risk population undergoing ultrasound examinations of anatomic structures
      and biophysical profile evaluations. For investigation of the influence of fetal
      maturity on biophysical profile evaluations, both the malformed fetuses and the
      controls were stratified into two gestational-age groups, 26-34 weeks and > 34
      completed weeks. Four parameters of the BPP, including (1) fetal breathing, (2)
      gross fetal movements, (3) fetal muscle tone, and (4) quantitative amniotic fluid
      volume, were divided into low (0-6) and high (8) total score subgroups. Tests of
      significance were done using chi 2 analysis, Student's t test or Fisher's exact
      test, as appropriate. Level of significance was set at P < .05. RESULTS: When
      comparing malformed fetuses to controls, the malformed group had a statistically
      significantly higher percentage of low BPP scores due to absent fluid, tone or
      breathing. Fetuses with a musculoskeletal anomaly were statistically
      significantly more likely to lose points for fetal movement (P < .02); fetuses
      with a genitourinary system anomaly lost points for fluid (P < .001), tone (P <
      .005) and breathing (P < .005); fetuses with a central nervous system anomaly
      lost points for tone (P < .02) and breathing (P < .001); and fetuses with a
      thoracic anomaly lost points for breathing (P < .002). There was no statistically
      significant difference in BPP scores between fetuses at 26-34 weeks' gestational
      age and fetuses > 34 completed weeks' gestational age. CONCLUSION: The two
      hypotheses were confirmed by the study results.

PMID- 9653700
TI  - Laparoscopic radical hysterectomy with low paraaortic, subaortic and pelvic
      lymphadenectomy. Results of short-term follow-up.
AB  - OBJECTIVE: To describe a detailed operative procedure for type III laparoscopic
      radical hysterectomy with bilateral low paraaortic, subaortic and pelvic
      lymphadenectomy. STUDY DESIGN: Between January 1992 and December 1995, eight
      patients with cervical carcinoma IA2 or IB1 underwent laparoscopic radical
      hysterectomy at China Medical College Hospital, Taichung, Taiwan, R.O.C. The
      procedure of laparoscopic radical hysterectomy was separated into eight segmental
      steps. RESULTS: No major complications, including ureteral injury and lymphocyst
      formation, were noted in any case. Mean hospitalization was 6.5 days. The follow
      up period ranged from 16 to 62 months. Only one case recurred, in the lung.
      CONCLUSION: Laparoscopic radical hysterectomy is a safe procedure. A complete
      pelvic and paraaortic lymphadenectomy and type III radical hysterectomy can be
      performed laparoscopically. This approach allows shorter hospitalization and
      carries less morbidity than the open type. Short-term follow-up (1.3-5.1 years)
      indicated a favorable prognosis.

PMID- 9653701
TI  - Lectin histochemistry of fallopian tube epithelial cells. Relation to ovum
      transport and ovum pickup.
AB  - OBJECTIVE: Data on histochemical and biochemical characteristics of the human
      oviduct are scarce. The exact mechanisms of ovum transport and pickup are not
      fully understood. STUDY DESIGN: Human fallopian tubes were obtained and prepared
      for histochemistry. We analyzed the distribution of negatively charged groups on
      the oviduct epithelium and cumulus cells and examined the distribution of
      glycoconjugates by means of lectin histochemistry. We tested the possible
      influence of poly-L-lysine and considered ABO blood group expression since these
      characteristics are determined by specific terminal sugar residues. RESULTS: A
      negatively charged glycocalyx exists on tubal epithelial cells and cumulus cells.
      Adherence by affinities similar to sugar-lectin binding forces could be disproven
      in case of commonly used lectins. Poly-L-lysine inhibited the cationic binding
      reaction but did not influence lectin binding. The blood group A glycoprotein
      presents terminal D-N-acetyl-galactosamine residues, which are demonstrated by
      HPA lectin binding. CONCLUSION: Our study indicates that it is unlikely that
      electrostatic interactions play a major role in ovum transport or pickup. Since
      poly-L-lysine has been described as inhibiting ovum transport, sugar-lectin
      binding affinities seem not to operate in ovum transport or pickup.

PMID- 9653702
TI  - Effect of danazol on the pregnancy rate in patients with unsuccessful in vitro
      fertilization-embryo transfer.
AB  - OBJECTIVE: To determine the effect of danazol on in vitro fertilization-embryo
      transfer (IVF-ET) patients who failed to conceive in previous attempts despite
      having embryos with optimal morphology, whether endometriosis is present or not.
      STUDY DESIGN: In this prospective, randomized, controlled study, of 81 patients
      who experienced unexplained failures of IVF-ET despite having good-morphology
      embryos, 40 received danazol (400 mg/d orally for 12 weeks) following the
      unsuccessful IVF-ET cycle. The next IVF-ET was performed within three months of
      the first spontaneous ovulation after danazol administration. The remaining 41
      patients constituted the control group, and in them the next IVF-ET was performed
      within six months after the previous failed cycle. RESULTS: Conception occurred
      in 16 of 40 (40%) danazol-treated patients at the subsequent cycle and showed a
      significant increase when compared with 8 of 41 (19.5%) control subjects (P <
      .05), though the number of embryos with optimal morphology decreased after
      danazol treatment. CONCLUSION: Danazol may be used for patients who have had
      repeated failures of IVF-ET despite having morphologically optimal embryos and
      may be useful for increasing receptivity of the endometrium in these patients.

PMID- 9653703
TI  - Vernix caseosa peritonitis as a rare complication of cesarean section. A case
      report.
AB  - BACKGROUND: Vernix caseosa peritonitis is a rare complication of cesarean section
      with distinctive histopathologic findings. CASE: Vernix caseosa peritonitis
      occurred in a 28-year-old, pregnant woman following emergency cesarean section.
      Exploratory laparotomy revealed right subphrenic and perihepatic fluid
      collections with multiple small abdominal abscesses. Cytopathologic examination
      of the peritoneal lavage specimen showed a purulent inflammatory exudate admixed
      with occasional squamous debris, portions of hair shafts, meconium pigment, and
      foamy and multinucleated giant cells. During hospitalization the patient had
      developed Clostridium perfringens acute endometritis, presumably due to
      aggressive treatment with broad-spectrum antibiotics. CONCLUSION: Pathologists
      are in a unique position to make the correct diagnosis in an otherwise-ambiguous
      clinical presentation because of the distinctive histopathologic and
      cytopathologic findings of this entity. Computed tomography-guided fine needle
      aspiration cytologic evaluation can be diagnostic in such cases.

PMID- 9653704
TI  - The lithium ion: a foundation for psychopharmacological specificity.
AB  - The idea of lithium's specificity for bipolar disorder was proposed in Cade's
      original work in 1949. Since then, many controlled studies have been performed,
      examining lithium for treatment of bipolar disorder and other psychiatric
      conditions. This review was undertaken to determine if the suggestion of
      lithium's specificity has support in the controlled studies conducted after
      Cade's initial proposal. Studies were selected in a Medline search, dating back
      to 1966 and also identified from the bibliography of some of these papers. The
      controlled trials with lithium for the treatment of mania and bipolar depression,
      unipolar depression, schizophrenia, and schizoaffective disorder were reviewed.
      The published studies with lithium in other neuropsychiatric conditions were also
      considered. Additionally, we reviewed literature on other therapeutic agents
      proposed for bipolar disorder, looking at their comparative effectiveness to
      lithium. The data analyzed give strong support for lithium's being most effective
      in bipolar disorder, with minimal or no therapeutic effects in other
      neuropsychiatric disorders. The neurochemical underpinnings of this specificity
      are being investigated, without conclusive findings to date. The study of this
      paradigm of specificity in neuropsychopharmacology research may lead to
      meaningful contributions to understanding the pathophysiology of bipolar disorder
      and may help to develop newer treatments for this condition.

PMID- 9653705
TI  - Has the effectiveness of lithium changed? Impact of the variety of lithium's
      effects.
AB  - Lithium treatment, initially considered specific for bipolar disorder, has since
      been shown to provide additional benefits in affective and other disorders. This
      variety of benefits should be taken into account when interpreting recently
      reported lower efficacy during lithium prophylaxis, as well as early relapses and
      loss of efficacy after lithium discontinuation. There are particularly striking
      parallels between these recent reports and earlier observations of
      "antipsychotic" lithium effects. Other factors, such as the accumulation of
      atypical, treatment-resistant patients in academic centers and, in particular,
      the broadening of diagnoses of affective disorders, further complicate the
      interpretation of the recent reports. Lithium, however, continues working well
      for patients with typical bipolar disorders, for whom it was originally proved
      effective.

PMID- 9653706
TI  - Bipolar disorders in DSM-IV: impact of inclusion of rapid cycling as a course
      modifier.
AB  - In this paper, we review the process for inclusion of rapid cycling as a course
      modifier to bipolar disorders in DSM-IV. This process involved definition of
      bipolar II disorder, delineating the duration of manic episode for bipolar I
      disorder, and clarification of the diagnosis of cyclothymic disorder and mixed
      mania.

PMID- 9653707
TI  - New concepts in mood stabilization: evidence for the effectiveness of valproate
      and lamotrigine.
AB  - Recognition of limited overall benefits from lithium in bipolar disorder, with
      even greater disadvantages in more severe forms of the disease, has spurred
      interest in alternative therapies. A long history of development of evidence for
      the utility of valproate has culminated in well-designed, placebo-controlled
      studies that establish the efficacy of the divalproex form of valproate in acute
      mania. Generally positive, but as yet not conclusive, studies indicate continued
      benefits in prophylactic treatment of bipolar disorder. The spectrum of efficacy
      of valproate is somewhat broader than that of lithium, extending to patients with
      certain more severe forms of the illness; e.g., mixed manics. Pretreatment plasma
      GABA activity was positively correlated with magnitude of improvement in manic
      symptomatology with divalproex. The evidence of comparable clinical benefits for
      lithium and valproate has stimulated studies that indicate overlapping effects on
      specific G protein-linked signal transduction for lithium and valproate, but not
      for carbamazepine. The possibility that additional antiepileptic drugs might have
      efficacy in bipolar disorder has encouraged early clinical studies with several
      newer antiepileptic drugs. Preliminary evidence for the efficacy of one of these,
      lamotrigine, has been presented.

PMID- 9653708
TI  - Lithium--early development, toxicity, and renal function.
AB  - The report of the effectiveness of lithium in the treatment of mania by John Cade
      was followed by a number of studies confirming his observations and developing
      guidelines for safe and effective use. Premature rejection of lithium on safety
      grounds denied many patients the benefit of treatment and may have cost more
      lives than it saved. A similar safety alarm was triggered by reports of kidney
      damage in the late 1970s. Subsequent reports have questioned the significance of
      anatomical findings, and functional impairment and relationship to lithium
      treatment. Recent findings support the conclusion that progressive impairment of
      glomerular and tubular function in patients during lithium maintenance is the
      exception rather than the rule and is related more to lithium intoxication,
      maintenance plasma lithium levels, concurrent medications, somatic illness, and
      age than on time on lithium. Guidelines for lithium use and monitoring of renal
      function are outlined.

PMID- 9653709
TI  - Beyond lithium in the treatment of bipolar illness.
AB  - Dramatic changes have recently occurred in the availability of treatment options
      for bipolar illness. Second generation mood stabilizing anticonvulsants
      carbamazepine and valproate are now widely used as alternatives or adjuncts to
      lithium. High potency benzodiazepines are also used as alternatives to typical
      neuroleptics, and now atypical neuroleptics are demonstrating efficacy and better
      side-effects profiles than the typicals. Thyroid augmentation strategies and
      dihydropyridine L-type calcium channel blockers require further clinical trials
      to define their role. Putative third generation mood stabilizing anticonvulsants
      lamotrigine, gabapentin, and topiramate have unique mechanisms of action and
      deserve further systematic study, as does the potential role for nonconvulsive
      brain stimulation with repeated transcranial magnetic stimulation (rTMS). These
      and a host of other potential treatment options now require a new generation of
      clinical trials to help identify clinical and biological markers of response and
      optimal use alone and in complex combination therapeutic regimens.

PMID- 9653710
TI  - Behavioral reversal of lithium effects by four inositol isomers correlates
      perfectly with biochemical effects on the PI cycle: depletion by chronic lithium
      of brain inositol is specific to hypothalamus, and inositol levels may be
      abnormal in postmortem brain from bipolar patients.
AB  - The inositol depletion hypothesis of lithium (Li) action has been criticized,
      because depletion of inositol after chronic Li treatment has not been
      reproducible, effects of inositol to reverse Li-induced behaviors occurred also
      with epi-inositol, a unnatural isomer, and because inositol is ubiquitous in
      brain and hard to relate to the pathogenesis of affective disorder. Therefore, we
      review our studies showing that lithium depletion of brain inositol occurs
      chronically in the hypothalamus, a region not previously examined; that
      behavioral effects of four different inositol isomers including epi-inositol
      correlate perfectly with their biochemical effects; and that inositol in
      postmortem human brain is reduced by 25% in frontal cortex of bipolars and
      suicides as compared with controls. Because inositol in postmortem brain is
      reduced and not increased in bipolar patients, the relationship between inositol,
      lithium, and affective disorder is complex.

PMID- 9653711
TI  - Effects of lithium on cAMP-dependent protein kinase in rat brain.
AB  - We have investigated the effects of lithium treatment on cAMP-dependent protein
      kinase in discrete brain areas of rat by using photoaffinity labeling as well as
      western blotting. Lithium administered for 5 weeks resulted in a significant
      increase of the cAMP binding to the 52 kDa cAMP-receptor in the soluble, but not
      in the particulate, fractions of both hippocampus and frontal cortex. Moreover,
      immunoblotting experiments revealed that chronic lithium treatment significantly
      increased the immunoreactivity against the regulatory and the catalytic subunits
      of the cAMP-dependent protein kinase in the soluble fraction of both brain areas.
      In contrast, no appreciable effect was observed in the particulate fractions.
      Short-term lithium treatment induced a significant increase in the immunolabeling
      of the catalytic subunits in the soluble fraction of both areas; whereas, the
      regulatory subunits and the actin were unchanged. In the particulate fractions,
      short-term lithium treatment did not elicit any substantial modification. Taken
      together, the results of the present study add to the growing evidence indicating
      that components of the cAMP signalling could play a crucial role in the
      biochemical action of lithium.

PMID- 9653712
TI  - Reductionism and antireductionism.
AB  - Reductionism is the idea that all of the complex and apparently disparate things
      we observe in the world can be explained in terms of universal principles
      governing their common ultimate constituents: that physics is the theory of
      everything. Antireductionism comes in two varieties: epistemological and
      ontological. Epistemological antireductionism holds that, given our finite mental
      capacities, we would not be able to grasp the ultimate physical explantation of
      many complex phenomena even if we knew the laws governing their ultimate
      constituents. Therefore we will always need special sciences like biology, which
      use more manageable descriptions. There may be controversy about which special
      sciences cannot be replaced by reduction, but that there will be some is
      uncontroversial. Ontological antireductionism holds, much more controversially,
      that certain higher-order phenomena cannot even in principle be fully explained
      by physics, but require additional principles that are not entailed by the laws
      governing the basic constituents. With respect to biology, the question is
      whether the existence and operation of highly complex functionally organized
      systems, and the appearance of self-replicating systems in the universe, can be
      accounted for in terms of particle physics alone, or whether they require
      independent principles of order.

PMID- 9653713
TI  - Reductionism in physical sciences.
AB  - The idea of reductionism in physical sciences is that all physicochemical
      observables can be described in terms of a limited number of particles and their
      variable energies. Here we limit ourselves to atomic descriptions showing how
      very successful reductionism is in treating equilibrium systems. This includes
      all properties of single molecules, even DNA, and can be extended to dynamic
      assemblies of molecules through the variables composition, potential energies,
      kinetic energies (temperature) and volume (pressure). This description includes
      the capacity of a system to change, to do work. It does not include working or
      changing systems when we have to consider time-dependent variables such as
      directed motion, flow. Analysis of such accidentally or purposefully directed
      activity seems, to the author, to be outside the above reductionist analysis in
      that its feature is organization around a 'plan' or a 'cycle'. Thus reductionism
      fails to describe machines, man-made or biological, in that the parts are
      arranged, even dedicated, to a total function.

PMID- 9653714
TI  - Macromolecular structure and self-assembly.
AB  - The output from the molecular biology revolution has grown steadily and
      logarithmically from the first protein sequence, insulin (Ryle AP et al 1955
      Biochem J 60:541-556), the first three-dimensional atomic structure of a
      macromolecule, myoglobin (Kendrew JC et al 1960 Nature 185:422-427), the first
      DNA gene sequence, phi X174 gene J (Sanger F et al 1977 Nature 265:687-695) and
      the first genome sequence for a free-living organism, Haemophilus influenzae
      (Fleischmann RD et al 1995 Science 269:496-512) to the current situation where
      the output rate is close to one new gene sequence every few minutes, several new
      three-dimensional structures a day and a new (bacterial) genome completed every
      few months. Those working in this field must readjust their horizons to this
      changing situation every year or two. In the area of three-dimensional structure
      of macromolecules and macromolecular assemblies, the methods of X-ray
      crystallography, nuclear magnetic resonance and electron microscopy have combined
      to produce powerful insights into how these molecular machines work. In this
      paper, I present three examples of molecular machines whose structure tells us a
      lot about how they work. These are the light-driven proton pump
      bacteriorhodopsin, the ATP synthetase molecule which contains a tiny motor and
      generator, and the flagellar rotary motor which provides the thrust to power
      physical movement of the bacterial cell. The structure itself in three
      dimensional detail is thus often seen to provide the most important single
      insight into how things work, reducing biology to chemistry and physics. The
      reductionist approach in this field seems to be limited only by the accuracy by
      which it is possible to describe inter- and intra-molecular interactions in terms
      of hydrogen bonds, van der Waals interactions and electrostatic forces. At
      present, there is no fundamental limit in sight.

PMID- 9653715
TI  - Reduction and integration in understanding the heart.
AB  - The heart provides an excellent example of the limits of the reductive approach.
      Cardiac cells function through the interaction of a very large number of ion
      transporters, and the processes that link these to metabolic states and to
      contraction. Yet, the great majority of the advances made recently have been at
      the cellular and molecular levels. The pressing problem now is to begin to
      understand the highly complex interactions that create physiological function at
      a cellular level and, in turn, to understand the way in which large numbers of
      cells interact to produce the activity of the whole heart. Many kinds of
      arrhythmia, for example, can only be understood at the whole organ level.
      Successful interventions using drugs designed to treat cardiac disease depend on
      an integrative understanding, which at present we do not have. This is one of the
      reasons why clinical trials of drugs treating cardiac arrhythmias have been
      spectacularly disappointing. This paper illustrates some of these problems by
      analysing normal and abnormal heart rhythms, and by focusing on one particular
      transporter, the sodium-calcium exchanger, that is deeply involved both in normal
      calcium balance in the heart and in the generation of pathological states,
      including life-threatening arrhythmias. It will be shown that some surprising
      counterintuitive results appear when computations are done at an integrative
      level.

PMID- 9653717
TI  - Reductionism and explanation in cell biology.
AB  - It is likely to be impossible or very difficult to provide a detailed description
      of the molecular interactions underlying all cellular phenomena. However, methods
      and ways of thinking are now available or being developed that can deal better
      with the complexity and greater extension in space and time found at the level of
      the cell. This will lead to the identification of some components or groups of
      components as being of particular importance for a cellular phenomenon which can
      then be studied in detailed molecular terms. In other cases detailed molecular
      characterization may be replaced by a logical description of the process which
      emphasizes the information flow and processing rather than the nature of the
      individual components and their interactions. This may provide an adequate
      explanation for an appropriate understanding of the cellular phenomena involved.

PMID- 9653716
TI  - Muscle contraction.
AB  - Understanding muscle contraction goes to the heart of one of the fundamental
      questions posed by classical philosophy, namely the nature of the pi nu epsilon
      upsilon mu alpha psi nu chi iota kappa omicron nu. The nature of 'understanding'
      has altered greatly during the last two millenia, particularly in response to the
      development of the concept of energy. Moreover, understanding contraction depends
      on understanding muscle structure. Galen was the first to make a detailed
      anatomical examination of the mode of action of muscles and recognized the heart
      as a muscle, but this line of research was not pursued until Leonardo da Vinci
      rediscovered it 1400 years later. Vesalius used the phrase Machina Carnis, but it
      was first Descartes who proposed a neuromuscular machine. However, the level of
      understanding of the physiology of muscle depends critically on the resolution of
      the available anatomy. Radical new insight was provided by electron microscopy.
      But an understanding at a physicochemical level is only possible if the
      structures of the components are known at atomic resolution. These have become
      known in the last five years and have led to dramatic progress. The present level
      of understanding of muscle is a physicochemical explanation of how the hydrolysis
      of ATP by the component proteins actin and myosin leads to movement.

PMID- 9653718
TI  - Biological computation.
AB  - It is argued that biological systems can be viewed as special computing devices.
      This view emerges from considerations of how information is stored in and
      retrieved from the genes. Genes can only specify the properties of the proteins
      they code for, and any integrative properties of the system must be 'computed' by
      their interactions. This provides a framework for analysis by simulation and sets
      practical bounds on what can be achieved by reductionist models.

PMID- 9653719
TI  - Reductionism in learning and memory.
AB  - This chapter examines the successes and (at least for now) failures of
      reductionist approaches in dealing with the problem of learning and memory.
      Beginning with the work of Pavlov on classical conditioning and the theoretical
      work of Hebb, the paper traces the contributions made by studies on Aplysia,
      Drosophila and long-term potentiation in the mammalian hippocampus.

PMID- 9653720
TI  - Hearing.
AB  - The aim of this chapter is to describe some of the features of the processing of
      the auditory world and how different levels of explanation are appropriate to the
      understanding of hearing. The working of the inner ear is best seen as a the
      operation of a purposefully structured machine for the extraction of biologically
      meaningful components from a sound. Physical scales determine in large part the
      appropriate description of the auditory system.

PMID- 9653721
TI  - The nested networks of brains and minds.
AB  - The reductionist approach to the brain shows promise of revolutionizing our ideas
      about what single neurons can do. A spine on a cortical pyramidal cell is about
      the size of a single Escherichia coli, and if the internal machinery of a spine
      is anything like as well organized as that of E. coli, the whole pyramidal cell
      with its 5000 spines must be capable of computations an order of magnitude more
      complex than those demanded of the neurons used for current models of the brain.
      These computations might enable single neurons to detect spatiotemporal patterns,
      i.e. Hebb's 'phase sequences'. Reductionism is apparently limited because its
      drive is to look for explanations at lower levels in the organizational tree. For
      this purpose it often uses isolated preparations in which such lower levels can
      be studied but higher levels cannot, because they have been thrown down the sink.
      Reductionism will never lead us to understand organization and interaction in
      parts discarded or ignored, and this must include the interactions between
      individual human minds that are crucial for understanding human society. Our
      brains possess a 'commentary system', a mechanism that can make reports on the
      internal status of some parts of the brain. This makes possible networks of
      minds, and the present meeting is such a network whose interactions are being
      recorded for posterity. On a grander scale such networking creates a cultural
      forum where communal goals and purposes are formulated, disseminated, modified,
      and often perpetuated in lasting form. The resulting group behaviour has obvious
      survival value, and is perhaps the feature that distinguishes humans most clearly
      from other species.

PMID- 9653722
TI  - Genes, environment and the development of behavior.
AB  - Explanations of where our behaviour comes from are frequently presented in terms
      of the exclusive importance of one set of factors, either genetic or
      environmental. Unravelling the external and internal sources of individual
      differences is a useful first step in analysing behavioural development.
      Nevertheless, the analytical method that was well designed for extracting
      influences from a confusing mass of data was never a substitute for a theory. It
      was simply a means to an end. Descriptive statements about the genetic and
      environmental sources of variation in the population do not offer an adequate
      basis for understanding what happens to individuals. That awareness was an
      important step in moving towards an adequate theory of behavioural development.
      As an example of how that may be done, I discuss the interplay between the
      developing individual and its environment in highly regulated learning processes
      such as imprinting. Getting the level of explanation right is crucial. A purely
      molecular or synaptic account of the processes involved in the development of
      behaviour is inadequate. Nevertheless, those connectionist models that are
      properly rooted in a thorough knowledge of behaviour and physiology do provide a
      promising route out of the reductionism and the empty interactionism that
      characterized the old nature-nurture debates.

PMID- 9653723
TI  - What is wrong with reductionist explanations of behaviour?
AB  - Methodological reductionism has served biology well, but its problems in the
      study of behaviour include turning open systems into closed ones, defining the
      units of analysis, and interpreting correlative and causal relationships between
      processes studied within different biological discourses, from molecular biology
      to psychology The problems become more acute when methodological becomes
      philosophical reductionism, with its declared goal of collapsing 'higher level'
      explanations into 'lower level' ones. Quite apart from the vexed question of what
      constitutes a 'level', relevant behavioural phenomena may only be manifest at
      such higher levels. The reductionist programme assumes that parts have
      ontological and possibly historical (developmental, evolutionary) primacy over
      wholes, yet the nature of living systems is such that this cannot be the case. I
      will exemplify these problems in the context of the study of behaviour. But the
      worst problem arises when reductionism becomes an ideology, especially in the
      context of human behaviour, when it makes the claims to explain complex social
      phenomena (e.g. violence, alcoholism, the gender division of labour or sexual
      orientation) in terms of disordered molecular biology or genes. In doing so,
      ideological reductionism manifests a cascade of errors in method and logic:
      reification, arbitrary agglomeration, improper quantification, confusion of
      statistical artefact with biological reality, spurious localization and misplaced
      causality.

PMID- 9653724
TI  - Levels of organization in ecological systems.
AB  - Broadly speaking, ecology seeks to understand the structure and dynamics of
      individual populations of plants and animals, of communities of interacting
      populations, and of ecosystems. Ideally--the reductionist dream--it would be nice
      to build such an understanding of how individual populations respond to
      disturbance upon a fundamental understanding of the behaviour and physiology of
      the constituent individuals. This is vastly ambitious. In practice, most
      successful applications of population biology, for instance to the management of
      harvested systems or to the control of pests and pathogens, have treated the
      population itself as the basic variable (in equations whose parameters are
      assessed phenomenologically, even though they are in principal derivable from the
      more basic parameters pertaining to the behavioural ecology of individuals). By
      the same token, studies of the structure and function of communities and
      ecosystems are often and usefully approached phenomenologically as things in
      themselves (topology of food webs, 'plumbing diagrams' of energy flows, etc.)
      rather than being derived in a more fundamental way from detailed consideration
      of the interaction among the constituent populations. Furthermore, at every level
      of approach, it is often difficult to perform meaningful experiments which
      control variables and isolate single factors in a tidy way. Frequently, the
      spatial or temporal scale is such that observational data and/or past records
      provide the only way to estimate parameters. In the 1970s and early 1980s this
      inability of much of ecology to conform rigidly to simplistic schemes of 'how
      science is done' caused much angst. In this paper I offer a grandly opinionated
      overview of these issues.

PMID- 9653725
TI  - The units of selection.
AB  - Darwin's idea of evolution by natural selection is almost universally accepted by
      biologists, but debate continues about the units of selection. The history of
      this debate starts with Wynne-Edwards' arguments for group selection, and
      Hamilton's explantation of social behaviour in terms of the inclusive fitness of
      individuals. Hamilton's approach differs from the gene-centred approach pioneered
      by Williams and Dawkins, although both the problem and its solution are
      essentially the same. The choice of approach depends on conceptual and
      mathematical simplicity, and on one's attitude to the causal efficacy of genes.
      The problem of selection on units above the species level is discussed. Today, we
      are in the main concerned with cases in which selection acts simultaneously at
      two levels. This is true of current research on intragenomic conflict and of the
      suggestion by Maynard Smith and Szathmary that in the major transitions in
      evolution, entities that were capable of independent replication before the
      transition can only replicate as part of a larger whole after it.

PMID- 9653727
TI  - "Hot beds of disease": malaria and civilization in nineteenth-century British
      India.
AB  - Malaria control was a relatively low priority for the British in India: despite
      being the principal cause of sickness and death among the Indian people, malaria
      affected the colonial economy only indirectly and, unlike epidemics of cholera or
      plague, presented few challenges to public order. Nevertheless, malaria was an
      important disease: not only in terms of its effects upon the health and
      livelihood of the indigenous population, but also in the language and politics of
      colonial rule. Malaria was a signifier of India's "backwardness" and its
      prevention was closely associated with the mission to "civilize" and tame the
      Subcontinent. But the gap between this rhetoric and the reality of colonial
      policy was unconvincingly wide, and the Government of India's failure to tackle
      the problem of malaria was increasingly criticised by imperialists and
      nationalists alike.

PMID- 9653726
TI  - The particular and the general. Issues of specificity and verticality in the
      history of malaria control.
AB  - Several ideas have currency through long periods of malaria control history and
      important issues in controlling many communicable diseases have often been fought
      out over malaria. Health administrators view complex problems of malaria control
      through these apparently simple ideas. The most important concepts concern the
      need for specific methods to combat particular features of the spread of malaria
      and how far this is reflected by the development of specific health services.
      This paper follows these ideas through the last century and argues that the dead
      hand of history has played too large a role in determining malaria control
      generally, and especially over the last two decades, while the whole period
      provides an illuminating commentary on conceptualization in tropical health and
      its evolution. The two decades following discovery of the mosquito transmission
      of malaria saw increasingly specific knowledge about the vectors and approaches
      to preventing breeding. This required "odd" health workers who poured oil on
      water and did fresh-water biology and later special engineers who could design
      reservoirs and irrigation systems hostile to anopheline breeding and apply
      "species sanitation". The expertise required lay outside the health sector.
      Later, the DDT phase focused on a single highly specialized control technique,
      total coverage house spraying, and led on to attempted eradication, whose
      activities were vertically grouped. Malaria eradication became autonomous within
      the health department. It became the archetypal vertical programme whose funding
      levels and early successes made it a model to be emulated. But the need for
      active case surveillance to be integrated with general health services was a
      major reason for failure in some countries. The subsequent reaction to failed
      eradication emphasized horizontal or general health services, and these are very
      relevant to current pre-occupations with morbidity and mortality reduction by
      early diagnosis and prompt treatment. The future needs a complex mixture of
      interventions that cut across traditional views of either specificity or of the
      horizontal/vertical split in programmes, and development of effective control
      with imperfect tools requires a more sophisticated analysis of control methods
      and organizations than is provided by a simple vertical/horizontal debate.

PMID- 9653728
TI  - "Reasons for contentment": malaria in India, 1900-1920.
AB  - Although Ronald Ross carried out his pioneering investigations on the role of the
      mosquito in the transmission of malaria in India, antimalarial activities in the
      sub-continent were disappointing. After the unsuccessful attempt at mosquito
      control at the military cantonment at Mian Mir (near Lahore, present day
      Pakistan), quinine prophylaxis was adopted as a compromise solution. While this
      strategy also failed, a good deal of important work was carried out in India in
      the first two decades of the twentieth century, so that by the 1920s, the
      magnitude of the malaria problem was fully appreciated.

PMID- 9653729
TI  - Antimalarial work in China: a historical perspective.
AB  - Systematic scientific studies of malaria in China did not begin until the 1920s.
      The persistence of misconceptions about the disease and the absence of political
      stability, funds and trained personnel were obstacles to any large scale
      antimalarial campaigns. In the 1920s and 30s, antimalarial efforts involved
      epidemiologic studies, environmental alterations, and treatment of patients.
      During the Sino-Japanese War when the Chinese government relocated inland,
      China's antimalarial work focused on the control of the disease, especially in
      the western and southwestern provinces. After the founding of the People's
      Republic of China in 1949, nationwide antimalarial campaigns were initiated and
      enforced by the central government which also promoted intersectoral and
      interregional cooperation. Together with the building of a preventive and anti
      epidemic infrastructure and health care system as well as the training of
      personnel, the government used techniques of mass mobilization to launch programs
      of vector control and mass therapy. Provinces were also organized into
      antimalarial regional alliances to facilitate malaria control and surveillance.

PMID- 9653730
TI  - Ecology, economics and political will: the vicissitudes of malaria strategies in
      Asia.
AB  - The documented history of malaria in parts of Asia goes back more than 2,000
      years, during which the disease has been a major player on the socioeconomic
      stage in many nation states as they waxed and waned in power and prosperity. On a
      much shorter time scale, the last half century has seen in microcosm a history of
      large fluctuations in endemicity and impact of malaria across the spectrum of
      rice fields and rain forests, mountains and plains that reflect the vast
      ecological diversity inhabited by this majority aggregation of mankind. That
      period has seen some of the most dramatic changes in social and economic
      structure, in population size, density and mobility, and in political structure
      in history: all have played a part in the changing face of malaria in this
      extensive region of the world. While the majority of global malaria cases
      currently reside in Africa, greater numbers inhabited Asia earlier this century
      before malaria programs savored significant success, and now Asia harbors a
      global threat in the form of the epicenter of multidrug resistant Plasmodium
      falciparum which is gradually encompassing the tropical world. The latter
      reflects directly the vicissitudes of economic change over recent decades,
      particularly the mobility of populations in search of commerce, trade and
      personal fortunes, or caught in the misfortunes of physical conflicts. The period
      from the 1950s to the 1990s has witnessed near "eradication" followed by
      resurgence of malaria in Sri Lanka, control and resurgence in India, the
      influence of war and postwar instability on drug resistance in Cambodia, increase
      in severe and cerebral malaria in Myanmar during prolonged political turmoil, the
      essential disappearance of the disease from all but forested border areas of
      Thailand where it remains for the moment intractable, the basic elimination of
      vivax malaria from many provinces of central China. Both positive and negative
      experiences have lessons to teach in the debate between eradication and control
      as alternative strategies. China has for years held high the goal of "basic
      elimination", eradication by another name, in sensible semi-defiance of WHO
      dictates. The Chinese experience makes it clear that, given community
      organization, exhaustive attention to case detection, management and focus
      elimination, plus the political will at all levels of society, it is possible
      both to eliminate malaria from large areas of an expansive nation and to
      implement surveillance necessary to maintain something approaching eradication
      status in those areas. But China has not succeeded in the international border
      regions of the tropical south where unfettered population movement confounds the
      program. Thailand, Malaysia and to an extent Vietnam have also reached essential
      elimination in their rice field plains by vigorous vertical programs but fall
      short at their forested borders. Economics is central to the history of the rise
      and fall of nations, and to the history of disease in the people who constitute
      nations. The current love affair with free market economics as the main driving
      force for advance of national wealth puts severe limitations on the essential
      involvement of communities in malaria management. The task of malaria control or
      elimination needs to be clearly related to the basic macroeconomic process that
      preoccupies governments, not cloistered away in the health sector Historically
      malaria has had a severe, measurable, negative impact on the productivity of
      nations. Economic models need rehoning with political aplomb and integrating with
      technical and demographic strategies. Recent decades in Chinese malaria history
      carry some lessons that may be relevant in this context.

PMID- 9653731
TI  - The role of chemotherapy in early malaria control and eradication programmes in
      Thailand.
AB  - The use of synthetic antimalarial compounds played a secondary role to the use of
      residual insecticides in post World War II antimalarial control and eradication
      campaigns. The discovery of chloroquine-resistant malaria in South East Asia and
      South America prompted an intensification of antimosquito measures, rather than a
      thorough investigation of resistance. It was the failure of the antimosquito
      measures which primarily called a halt to malaria eradication and a return to
      control. A focus on the role of synthetic antimalarials in Thailand thus aims to
      provide a complementary view to those histories being constructed around the
      antimosquito measures.

PMID- 9653732
TI  - Malaria control in Papua New Guinea in the Second World War: from disaster to
      successful prophylaxis and the dawn of DDT.
AB  - Australian forces were involved in warfare in hyperendemic areas of New Guinea
      from early 1942 until late 1945. Initially they were ill-prepared and suffered
      very heavy malaria casualties, even when not engaged in fighting. As a result
      measures were taken to make the supervision of personal protection (clothes,
      suppressive atebrin, repellent, mosquito nets) a matter for unit commanders
      rather than a medical problem. Malariologists were appointed and supervised
      Malaria Control Units, which were moved in with attacking troops, and
      Entomological Sections were established, which provided advice on vectors of
      malaria and other arthropod-borne diseases. In successive campaigns the
      casualties from malaria decreased substantially, especially after active
      operations in particular campaigns had ended, except in the Aitape-Wewak area,
      where field observations suggested that some strains of P. falciparum were
      resistant to the standard dose of suppressive atebrin. This was confirmed in
      experiments on human volunteers at a malaria research unit in Australia.

PMID- 9653733
TI  - Malaria in New Guinea during the Second World War: the Land Headquarters Medical
      Research Unit.
AB  - In June 1943 arrangements were made to carry out experiments on malaria
      suppressive drugs on human volunteers in Cairns, in north Queensland, under the
      direction of Brigadier Neil Hamilton Fairley; early in 1944 the Land Headquarters
      Medical Research Unit was established to continue this work. Using 868 healthy
      volunteers and 317 infected soldiers and A. punctulatus mosquitoes flow in from
      New Guinea or bred locally, several suppressive drugs were tested. Doses of 10
      grains of quinine daily failed to suppress New Guinea strains of P. falciparum
      and were only partially effective against P. vivax infections, whereas 100 mg of
      atebrin daily controlled symptoms of P. vivax infection and cured infections with
      most New Guinea strains of P. falciparum, however some strains of P. falciparum
      from Wewak were resistant to this dose, but were cured with double the daily
      dose.

PMID- 9653734
TI  - Bitter-sweet solutions for malaria: exploring natural remedies from the past.
AB  - This paper explores "a wonderful cure" for malaria used successfully by Robert
      Talbor, an apothecary's apprentice in the English marshes, to treat Essex
      smugglers and European Royalty in the seventeenth century. The basis of this cure
      is identified as "quinquina" from the bark of the South American Cinchona tree.
      The story of Robert Talbor and his secret remedy for malaria opens up a set of
      intriguing questions about the early history of "quinquina", the subsequent
      development of quinine, the use of higher plants for antimalarial drugs,
      including the Chinese plant Artemisia annua L., and the value of unlocking the
      secrets of the past in our search for strategies to control malaria.

PMID- 9653735
TI  - Malaria and colonialism in the German colonies New Guinea and the Cameroons.
      Research, control, thoughts of eradication.
AB  - German malaria research during the colonial period took place between medical and
      political interests. In the field of zoological and clinical research of malaria
      Germany was not a pioneer. Nevertheless, Robert Koch forced by impressive Italian
      results tried to participate in malaria research on the field of acquired malaria
      immunity and by optimizing the therapeutic doses of quinine in German New Guinea.
      In the German Cameroons, on the other hand, the fight against malaria was
      completely dominated by racial and political arguments. The paper tries to shed
      light on this dichotomy, which turned out to be not very productive.

PMID- 9653736
TI  - Unum facere et alterum non omittere: antimalarial strategies in Italy, 1880-1930.
AB  - At the end of the XIXth Century the attitude towards malaria changed dramatically
      from fatalism and resignation to an active policy that made the eradication of
      the disease a possible objective. This dramatic change in the scientific
      political and cultural attitudes towards malaria was the result of two main
      phenomena: i) the impact of the scientific medicine and Pasteurian revolution on
      medicine and health policies, and ii) the discovery of the theoretical simplicity
      of the cycle of malaria transmission and of the possibility to interrupt it, by
      avoiding the contacts between people and the Anopheles mosquitoes. However,
      scientifically based strategies against malaria were in place before the
      discovery of the real causative agents and of the transmission cycle at the end
      of the XIXth century, as the origin of the scientific medicine had already
      produced a 'rationale' for local and national campaigns against malaria.
      According to Tommasi-Crudeli, for example, the cause of malaria was not a
      'chemical compound', a 'miasma', but a 'living ferment', specific and autonomous.
      As a consequence, the aim of antimalarial measures was to eliminate the
      conditions indispensable to the multiplication of the specific ferment contained
      in the soil. The theory of malaria aetiology changed after the discovery of the
      transmission cycle by Ross and Grassi, but the general strategy remained the
      same: to eliminate one of the factors indispensable to the multiplication and
      diffusion of the agent. The detailed knowledge of the malaria transmission cycle
      made it possible to define the exact conditions which were alone responsible for
      the propagation of the disease and its persistence in the endemic areas. The
      theoretical linearity and the specificity of the 'Grassi's law' was decisive and
      produced a fundamental paradigmatic shift in the antimalarial policies. The
      essential point for the epidemiology and prophylaxis of malaria became to clarify
      the conditions which contribute to facilitate or to prevent the infection of the
      Anopheles.

PMID- 9653737
TI  - Socio-economic and scientific premises for forming the strategies against malaria
      in Russia under Soviet power.
AB  - The rapid spread of malaria in the 1920s-early '30s in the USSR was a result of
      Stalin's social and demographic policy. The Soviet government needed to elaborate
      the special complex of organisational and applied scientific measures concerning
      the eradication of malaria. The Central Malaria Commission and a network of
      antimalaria stations were created. In the 1930s and '40s malaria studies were
      institutionalised. A system of Medical Research Institutes was set up in the
      Soviet Union. Antimalaria congresses and periodical special issues helped
      coordinate their activities. Russian parasitologists worked out new approaches
      and methods of the comprehensive control of malaria foci. During World War II
      (1941-1945), the epidemiological situation was aggravated and antimalaria
      measures reduced. In the years 1945-1960 Beklemishev with his scientific school
      worked out the concept of landscape malariology and of "vital scheme of the
      species". This concept formed the basis for realising the malaria eradication
      strategy. In 1961 the WHO Malaria Eradication Department ascertained the
      liquidation of all types of malaria in Russia as epidemics.

PMID- 9653738
TI  - Acquired immunity against malaria as a tool for the control of the disease: the
      strategy proposed by the Malaria Commission of the League of Nations in 1933.
AB  - The Third General Report of the Malaria Commission, printed in 1933, suggested
      for the control of malaria a strategy aimed to promote the acquisition of a
      "relative immunity" through a non radical treatment of the infected people living
      in highly endemic areas. The paper discusses the content of the Report and
      describes the scientific (empirical) premises on which it stood. Moreover, it
      illustrates the criticism that was directed against the immunological strategy
      and that eventually led to its abandonment.

PMID- 9653739
TI  - Failure-as-success: multiple meanings of eradication in the Rockefeller
      Foundation Sardinia project, 1946-1951.
AB  - In the history of malaria control programs there were important tensions between
      proponents of the concept of eradication and those of malaria control. In this
      debate the concept of eradication has had multiple meanings. This paper concerns
      the post-hoc interpretations of the outcomes of the Rockefeller International
      Health Foundation-sponsored project conducted in Sardinia between 1946 and 1951.
      The Ente Regionale per la Lotta Anti-Anofelica in Sardegna (regional agency for
      the anti-Anopheles struggle in Sardinia) (ERLAAS) project was conceived as a
      large-scale, field-based pilot demonstration project to test the feasibility of
      the strategy of "species eradication" in an area with an endemic malaria vector.
      Species eradication, a strategy championed by Soper, was aimed at the total
      annihilation of an anopheline vector from an area. Under the leadership of the
      Rockefeller Foundation, the ERLAAS project used postwar UNRRA funds to purchase
      local labor and imported DDT, oil-suspension, and war-surplus equipment in an
      "all-out" campaign against Anopheles labranchiae, even in sparsely populated
      areas. The original aim was entirely entomological; species eradication was
      expected to be completed in two years for a cost of $2.7 million. Ironically,
      malaria mortality on the island had already been lowered before WWII by a series
      of public health interventions. The ERLAAS project encountered severe technical
      and logistical difficulties; its ultimate failure was foreshadowed in the
      resignation of the first American director who doubted the feasibility of species
      eradication. Ultimately, the ERLAAS project was ended after four and a half years
      and an expenditure of $11.2 million. Although new malaria transmission on the
      island ended the project failed to eliminate A labranchiae. Finally, the regional
      government was counselled to continue mosquito control efforts; the continuation
      of a substantial mosquito control program for fifty years after this famous
      "malaria eradication" project runs contrary to the basic cost/benefit logic of
      the eradication concept. Nevertheless, in the popular press both in the U.S. and
      Italy, the project was presented and heralded as a major success in liberating
      the island from the age-old stranglehold and misery of malaria. In the course of
      the project, the goals of ERLAAS became transformed from species eradication to
      malaria eradication; this was an important political spin that was put on the
      evaluation of the program. The consequences of this tactical change in discourse
      included two important facts: the contribution of the Rockefeller Foundation to
      the island was exaggerated, and the legitimacy of the concept of global
      eradication was maintained. In the framework of the World Health Organization and
      the agreement for a global malaria eradication program, the "failure" of the
      Sardinia project was seldom recognized or mentioned. The technical, economic, and
      logistical problems faced by ERLAAS were very similar to the problems associated
      with the end of the WHO global malaria eradication policy in 1972. The Sardinia
      project is presented as a case of "failure-as-success"; an ideological
      transformation was made, not simply for local political expediency, but more
      importantly because of the predominance of the modernist cultural model of
      "progress through technology" that characterized international Public Health in
      the postwar era.

PMID- 9653740
TI  - Anopheles (malaria) eradication in Cyprus.
AB  - The island of Cyprus was suffering for many years from malaria fever. It was only
      in 1946 when a well organised Anopheles eradication campaign started. For this
      purpose the Anopheles Eradication Service was formed. Until 1949 this Service
      worked on Mosquito Eradication. An official announcement about the success of
      this Campaign was made on January 10th, 1950.

PMID- 9653741
TI  - Eradication, control or neither? Hookworm vs malaria strategies and Rockefeller
      Public Health in Mexico.
AB  - Malaria's epidemiological importance in Mexico greatly exceeded that of hookworm,
      but the Rockefeller Foundation (RF) paid far more attention to hookworm. Although
      the RF collaborated with malaria campaigns around the world, malaria was only
      incidental to the RF's activities in Mexico. The hookworm campaign, on the other
      hand, involved the RF at every stage, from conceptualization and design to
      financing, hiring, and day-to-day administration. This paper seeks to understand
      why the RF's involvement in Mexico differed for the two diseases and what the
      organizational, political, and health implications were for these divergent
      approaches. Beginning in the mid 1920s the Mexican government developed a modest
      anti-larval service, periodically draining and filling ditches and swamps,
      dusting Paris green, petrolizing stagnant water, and administering quinine.
      Following the RF's 1927 shift towards scientific investigation, it began to
      sponsor small-scale malaria research, collecting climatological, entomological,
      epidemiological, and clinical information. The Mexican government eagerly
      petitioned the RF to join a national effort, but it was reluctant to become
      involved. A National Malaria Campaign was established in 1935 under President
      Lazaro Cardenas to coordinate education, sanitary engineering, and treatment. The
      popular Campaign followed RF strategies even without its direct participation.
      Meanwhile, the RF avidly pursued modest malaria research in Mexico, funding U.S.
      investigators to conduct experiments on pesticides, mosquito-trapping, and
      controversially, watering methods for rice. These efforts culminated in the
      world's first field trial of DDT against louse-borne typhus and later as a
      residual spray for malaria. In the end the RF used Mexico as a convenient locale
      for scientific research that had global implications but only an incidental
      relationship to Mexico's own Malaria Campaign. Likewise, the RF's much more
      active hookworm program was more a means than an end, leading not to eradication
      of the disease, but to Mexico's commitment to modern public health organization
      and methods.

PMID- 9653742
TI  - The dawn of DDT and its experimental use by the Rockefeller Foundation in Mexico,
      1943-1952.
AB  - The Rockefeller Foundation played an important early role in promoting the use of
      DDT for malaria control. During World War II the Foundation helped test DDT in
      the United States. North Africa and Italy. From 1945 to 1952 the Foundation
      carried out an experimental anti-malaria program in Mexico as part of its global
      mission to diffuse knowledge of how to control malaria-bearing mosquitoes with
      DDT.

PMID- 9653743
TI  - Conforming strategies of public health campaigns to disease specificity and
      national contexts: Rockefeller Foundation's early campaigns against hookworm and
      malaria in Brazil.
AB  - The early experience of Rockefeller Foundation in Brazil, starting in 1915,
      reflected the idea of extending learned experience in Southern US to a wide
      international context. Health education and the creation of permanent local
      health services were expressed as main guidelines for cooperation with State and
      federal Brazilian agencies. Translating to the shaping of public health models
      the terms of scientific hygiene associated with the pastorian revolution, RF
      pictured different actions as part of a three step rationale of survey,
      experiment and demonstrations. In this paper we focus on Lewis Hackett's
      campaign, designed as a demonstration campaign of the "intensive method" of
      hookworm control, with the final purpose of enlisting local agencies in long-term
      action (1919-1924) and the malaria campaign in Rio de Janeiro State Lowlands
      (1922-1928) led initially by Mark Boyd as an "experimental control work" of field
      observation, campaign, control and maintenance to set guidelines to malaria
      control in tropical areas. The course and ultimate results of these experiences
      showed the need to adapt formal models to complex national and State-building
      context and to disease specificity, leading to pragmatic adaptations in the issue
      of control and eradication and on the shaping of vertical and horizontal health
      services. The failure of these two experiences in terms of disease control helped
      to strengthen the move, predominant in the next two decades, to vertical
      campaigns with least dependency on local social and political dynamics, as in the
      exemplar case of Frederick Soper's Anopheles gambiae eradication campaign (1938
      1942).

PMID- 9653744
TI  - The meanings of control and eradication of malaria in the Andes.
AB  - For centuries Peruvians distinguished malaria from other conditions with
      different names in Spanish and in the native languages because it was a frequent
      occurrence in the coast and in the jungle located in the west and east of the
      Andean highlands. Frequency in different local contexts generated different
      meanings of malaria that appear more clearly when studying the campaigns of
      control and eradication of the 20th century. These meanings played an important
      role in the divisions and tensions that cross race, national integrity, and
      regional identity in this Andean country. This work deals with the medical and
      social dimensions of malaria's control and eradication efforts and the ways in
      which they codified geographical and racial distinctions within peru. Because
      malaria does not develop in the highlands, Andean migrants to the coast and the
      jungle regions are particularly susceptible. Some doctors associated the disease
      with Andean people, even contending that it was an indication of "Indians"
      weakness. Finally, this article analyses the spread and containment of malaria in
      light of the world eradication campaign initiated in the late 1950s and with
      regard to mass migration, urbanization, and other 20th-century phenomena.

PMID- 9653745
TI  - Water won't run uphill: the New Deal and malaria control in the American South,
      1933-1940.
AB  - During the 1930s the United States Government poured significant funds into
      malaria control, via a variety of New Deal agencies. These projects were largely
      confined to drainage of mosquito-producing wetlands. Malaria had diminished
      significantly by the early 1940s, and this paper queries whether that reduction
      was due to the control projects of the thirties, and, if so, whether such
      projects should be a model for the current developing world, where malaria is a
      growing problem today. Malaria statistics from the 1930s and 1940s are
      unreliable, making this assessment, from the outset, complex. Further, the so
      called "malaria projects" from the 1930s were, in fact, poorly planned "make
      work" enterprises promoted by the Works Projects Administration and its ilk for
      the creation of unskilled, ditch-digging jobs. The drainage work lacked the
      oversight of competent engineers (many of them proving, in fact, that water
      wont's run uphill), and little of the work had permanent impact as the ditches
      were not maintained. Further, the work was not necessarily concentrated in
      malarious areas, since the unemployed's distribution did not overlap that of
      greatest mosquito density. Of the conflicting goals--unemployment relief and
      malaria control--the former consistently dominated the latter. The results were
      predictable. The author suggests that the depopulation of the rural south in the
      late 1930s had more of an impact (albeit indirect and unintended) on the malaria
      rates than did the large sums spent allegedly for the purpose of malaria control.

PMID- 9653746
TI  - Cognition and the global Malaria Eradication Programme.
AB  - When making a decision involves the analysis of complex cause-effect
      relationships, experts are normally consulted to describe the best options
      available. The global Malaria Eradication Programme relied upon the advice of a
      small group of experienced malariologists; their counsel directed the most
      ambitious endeavour in the history of the World Health Organisation. In this
      essay 1 week to show how that group behaved with a single purpose and ultimately
      grew to be greater than the sum of its parts because of the control of knowledge.
      Each member of this epistemic community was willing to battle against malaria as
      soon as possible--forsaking research, traditional tools, and risking disastrous
      epidemics--because they believed that residual insecticides could progressively
      eradicate a disease that killed millions and sapped the lives of countless more.
      Alternative methods were ridiculed; and the epistemic community used their
      individual prestige to insert the DDT gospel into the technical forums of the
      WHO, and the power (and money) forums of the USA. Particular knowledge structures
      of the post-war decade nurtured a technical solution to malaria, and we shall
      explore how the WHO and the epistemic community could grow within this
      environment so compatible to their praxes.

PMID- 9653747
TI  - 'No other logical choice': global malaria eradication and the politics of
      international health in the post-war era.
AB  - In 1955 the Eighth World Health Assembly voted to initiate a program for the
      global eradication of malaria. The global eradication of malaria represented a
      remarkable leap of faith. Many health authorities, both within and outside the
      Assembly, viewed eradication as at best fool hardy, and at worst, potentially
      disastrous. To understand why the World Health Assembly went ahead with a Global
      Eradication strategy, despite these concerns, it is necessary to examine the
      politics of international health and development in the post-war era. This
      political context shaped decisions about the adoption of DDT as a primary tool in
      the fight against malaria, as well as the adoption of the Malaria Eradication
      Program. It is equally important to understand how the advocates of an
      eradication strategy shaped arguments and developed support for their cause in
      the years leading up to the Eighth World Health Assembly meeting.

PMID- 9653748
TI  - Arnoldo Gabaldon's independent path for malaria control and public health in the
      tropics: a lost "paradigm" for WHO.
AB  - Arnoldo Gabaldon played a critical role in the early promotion of the belief that
      malaria could be eradicated in tropical countries. Under his leadership Venezuela
      was able to achieve dramatic progress, but nation-wide eradication was not
      realized. The path that Venezuela followed for malaria differed significantly
      from the WHO eradication strategy. Also, Gabaldon's public health approach,
      within which his malaria programme developed, was at odds with WHO's Basic Health
      Services (BHS) approach. The paper describes these differences and shows that
      approaches, similar to those subsequently pursued by Gabaldon, had been promoted
      in the early years of WHO's history but were quickly subsumed by that of BHS
      which came into force in 1953 and lasted until 1973. The paper concludes that, by
      remaining loyal to the global eradication of malaria, malariologists isolated
      themselves and lost much of their influence on the development of WHO public
      health policies and approaches.

PMID- 9653749
TI  - Conceptual conflict: malaria control and intermecine warfare within a London
      postgraduate school.
AB  - For more than twenty years after the end of World War II, uneasy relations
      existed between epidemiologists and protozoologists within the London School of
      Hygiene and Tropical Medicine, reflecting differences in their individual
      approaches to malariology and malaria control. The paper explores the particular
      problems created by the polarised views and lack of sympathy between George
      Macdonald and P.C.C. Garnham throughout the 1950s and 1960s.

PMID- 9653750
TI  - The end of malaria in Europe: an eradication of the disease by control measures.
AB  - The success of the campaigns against malaria in Europe, the USA and other
      countries in the temperate zone, prompted WHO to launch its global eradication
      campaign in 1955. It failed to achieve eradication in tropical countries due to
      climatic, social and economic conditions different from those prevailing in the
      temperate zone, where eradication had been achieved using control measures.

PMID- 9653751
TI  - Water-solid interactions. IV. Influence of moisture sorption on the compaction of
      film-coated particles.
AB  - The effect of moisture sorption on the compaction properties of model modified
      release (MR) pellets coated with ethyl cellulose/hydroxypropylcellulose film has
      been studied for the MR pellets alone and in binary mixtures with
      microcrystalline cellulose, lactose alpha-monohydrate, or lactose 9% amorphous.
      The in vitro dissolution rate prior to and after compaction was used as an
      indirect method of evaluating the effect of exposing the MR pellets to a
      compaction force. Moisture sorption as well as the glass transition temperature
      (Tg) using differential scanning calorimetry (DSC) were determined as a function
      of humidity for cast film conditioned at different humidities using a climate
      test chamber. The compaction properties of lactose and microcrystalline cellulose
      were altered by the addition of MR pellets, resulting in a robust tablet mass and
      a tensile strength of the tablet masses that was less sensitive to moisture. The
      amount of moisture sorbed was found to have little influence on the formation of
      cracks or on the rupturing of film-coated MR pellets during compaction. This was
      probably a result of both the small depression in the Tg for the film system at
      increasing RH and the robustness of the film chosen. The results also showed that
      the volume reduction properties of the tableting excipients were of importance
      for reducing damage to the film coating. Lactose had a higher protective effect
      on the film-coated MR pellets compared to microcrystalline cellulose.

PMID- 9653752
TI  - A logical stepwise approach to laser diffraction particle size distribution
      analysis methods development and validation.
AB  - In this study, a logical, stepwise, efficient approach was used to develop and
      validate particle size distribution analysis methods for 58 different
      pharmaceutical bulk powders in a timely fashion. Image analysis was used to
      determine particle morphology and laser diffraction particle size distribution
      analysis was used to evaluate the dispersion medium, dispersion concentration,
      sonication time, and dispersion stability. Ruggedness validation was performed,
      by two different analysis, on different days, with different instruments on two
      preparations each of two different lots of material. It was determined that if
      the relative standard deviation (RSD) of the median volume diameters (d50) of the
      four preparations for each lot was below 20%, the method was suitably rugged for
      use in a quality control setting. Data for methyldopa, metoprolol tartrate, and
      metronidazole are presented as typical method validation results for three
      different modes of analysis. Data at three points (d10, d50, and d90) on the
      distributions were tabulated and evaluated for all 58 methods validated. The
      median volume diameter (d50) was found to be adequate for method validation. The
      approach rapidly generated valid, reproducible particle size distribution
      analysis methodology.

PMID- 9653753
TI  - Formulation and evaluation of albuterol metered dose inhalers containing
      tetrafluoroethane (P134a), a non-CFC propellant.
AB  - This study was undertaken to evaluate tetrafluoroethane (P134a) as a possible
      chlorofluorocarbon (CFC) replacement for albuterol metered dose inhaler (MDI)
      formulations. Preformulation studies using three conventional (oleic acid,
      sorbitan trioleate, lecithin) and a nonconventional (oleyl alcohol) surfactant
      indicated that P134a is a poor solvent for these surfactants. A slight
      improvement in the solubility of oleic acid and oleyl alcohol was observed by the
      addition of low concentrations of a nonconventional cosolvent diethyl ether (< or
      = 0.5% w/w). Formulation screening of the prepared albuterol formulations
      indicated that suspensions containing oleyl alcohol and diethyl ether had a
      slower rate of separation. Product performance of four albuterol formulations
      containing oleyl alcohol, diethyl ether, and P134a was evaluated and compared to
      a leading commercial formulation containing CFC propellants (Ventolin). Ventolin
      showed excellent agreement between the emitted dose and the expected dose but
      only a reasonable agreement was observed with one of the better P134a-containing
      formulations. P134a formulations showed higher internal pressure in comparison to
      the CFC formulation. The concentrations of the surfactant, drug, and cosolvent
      appeared to have a significant impact on the uniformity of the emitted dose.
      Determination of particle size using the time-of-flight and the laser diffraction
      analyzer revealed that P134a formulations had equal or smaller particle size than
      the formulation containing CFC. However, the CFC formulation showed a higher
      respirable fraction than the P134a formulation when measured by the two inertial
      impaction methods. The observed particle size distribution of the formulation
      appeared to depend on the measuring method used.

PMID- 9653754
TI  - The influence of tertiary butyl alcohol and volatile salts on the sublimation of
      ice from frozen sucrose solutions: implications for freeze-drying.
AB  - The purpose of this work was to investigate the phase behavior of tertiary
      butanol (TBA) and volatile ammonium salts in frozen mixtures with some commonly
      used excipients and the efficacy of such volatile additives in accelerating the
      sublimation of ice from frozen solutions. Differential scanning calorimetry was
      employed to determine first-order phase transformations and glass transition
      temperatures in binary and ternary mixtures. Ice sublimation rates were studied
      by conventional freeze-drying and mass loss with time. A eutectic temperature
      (268 K) was identified for the anhydrous TBA-sucrose system. In frozen ternary
      water-excipient-TBA systems, the relative amplitudes of the glass and phase
      transitions, as measured during warming scans, were found to depend critically on
      the previous cooling rates. Glass transitions of all the freeze-concentrated
      mixtures used were determined. The sublimation studies indicated an ability of
      all volatile additives to accelerate ice sublimation from amorphous, freeze
      concentrated solutions, but no clear ranking order, applicable to all systems
      studied, could be established.

PMID- 9653755
TI  - A stability study involving HPLC analysis of aqueous thiorphan solutions in the
      presence of human serum albumin.
AB  - The stability of thiorphan (1.0 mg/ml) in normal saline containing 1% human serum
      albumin (HSA) was determined in order to find the most appropriate storage
      conditions. Direct liquid chromatographic analysis of this solution was feasible
      through the use of a micellar chromatographic system and proved to be stability
      indicating. During 8 weeks the percentages of the initial thiorphan concentration
      remaining after storage at 4, 20, 30, and 50 degrees C were determined. An
      Arrhenius plot was composed using the rate constants of thiorphan degradation at
      these temperatures. The thiorphan solution was stable for at least 2 months if
      stored at -20 degrees C. Taking into account the oxidative degradation of about
      7% after thawing, we determined that the solution can be kept in a refrigerator
      for 4 days. Storage at room temperature should be limited to 1 day. By
      identification of the degradation products it could be concluded that thiorphan
      is degraded mainly via oxidation forming disulfides. Therefore, it is recommended
      that the solvent be purged with nitrogen before thiorphan is dissolved.

PMID- 9653756
TI  - Formulation and characterization of calcium alginate beads containing ampicillin.
AB  - The purpose of this work was the preparation and characterization of calcium
      alginate beads containing ampicillin. Aqueous solutions of drug and sodium
      alginate (three viscosity grades) were added drop by drop to aqueous solutions of
      calcium chloride; the droplets instantaneously formed gel beads, which were then
      dried. Morphological studies and drug contents, in vitro release, and erosion
      tests were carried out for the characterization of the prepared beads. The dried
      particles were characterized by irregular shape and a smooth or rough surface,
      depending on the viscosity grade of the alginate used. The control of the drug
      for different time intervals depended on the molecular weight of the polymer
      used; however, the pH-change test showed that this capacity was much lower in the
      case of acid-treated particles. The results obtained show that the ampicillin
      beads prepared are suitable for intramammary therapy.

PMID- 9653757
TI  - The synthesis and in vitro characterization of the mucoadhesion and swelling of
      poly(acrylic acid) hydrogels.
AB  - The purpose of this research was to synthesize insoluble, mucoadhesive hydrogels
      by crosslinking linear poly(acrylic acid) with sucrose and investigate the
      relationship between hydrogel crosslink density, swelling, and in vitro
      mucoadhesion. A condensation reaction was employed to synthesize the hydrogels
      and crosslink density was varied by altering sucrose concentration and cure time.
      Equilibrium swelling at pH 7.4 was measured both gravimetrically and
      geometrically. In vitro mucoadhesion was determined by a tensile technique.
      Equilibrium swelling studies indicated that the crosslink density was
      proportional to both sucrose concentration and duration of cure time. In vitro
      mucoadhesive properties of the hydrogels improved as crosslink density increased.
      This was attributed to an increase in poly(acrylic acid) chain density/unit area
      of the equilibrium swollen hydrogel, which promoted interaction of the
      mucoadhesive and glycoprotein polymer chains.

PMID- 9653758
TI  - Detection of formaldehyde-induced crosslinking in soft elastic gelatin capsules
      using near-infrared spectrophotometry.
AB  - The purpose of this research was to monitor the migration of formaldehyde from a
      polyethylene glycol (PEG) fill into the gelatin shell of a soft elastic gelatin
      capsule (SEGC) using near-infrared (NIR) spectrophotometry. SEGCs were filled
      with five solutions of aqueous formaldehyde in PEG (0, 0.05, 0.10, 0.20, and 0.40
      v/v%), stored at ambient conditions for 48 hr, emptied, and scanned in NIR
      spectrophotometer. Principal component regression (PCR) was employed to analyze
      the spectra of the empty capsules. Good correlation was established (r2 = 0.988)
      when actual concentrations of formaldehyde in the PEG fill of the capsules were
      regressed against the principal component (PC) values from NIR spectra of the
      emptied and washed capsules. The loadings of the first PC describe a baseline
      shift in the spectra that arises from a change in water concentration. Lower PC
      loadings reveal the presence of signals at 1780 and 2200 nm that are not due to
      water absorbance, confirming the hypothesis that chemical bonds are formed during
      the formaldehyde-induced crosslinking of the gelatin in SEGCs. Gelatin
      crosslinking, initiated by formaldehyde migration from the PEG fill into the
      shell of an SEGC, was detected by NIR spectrophotometry. When NIR was coupled to
      principal component analysis, a linear relationship was found between the NIR
      spectra of empty SEGCs and the amount of crosslinking induced by concentrations
      of formaldehyde in the original fill material.

PMID- 9653759
TI  - In situ salt screening--a useful technique for discovery support and
      preformulation studies.
AB  - The purpose of this paper was to present an in situ salt screening technique
      which is applicable to most basic compounds. The theoretical aspects,
      experimental details, applications, and significance of this technique are
      illustrated through in situ salt screening studies performed on GW1818, an alpha
      1A andrenergic receptor antagonist intended for treatment of benign prostatic
      hyperplasia (BPH). Generally, the in situ salt screening technique includes (i)
      acid selection, (ii) a solubility study, (iii) characterization of residual
      solids, and (iv) calculation of the Ksp and solubility of the salts. Six acids
      were screened for salt formation with GW1818. Excellent agreement was found
      between the solubility results determined using the authentic salts and
      solubility results obtained through in situ screening. Additional evidence of
      salt formation and some solid state properties of the salts formed in situ were
      obtained through microscopic examinations, differential scanning calorimetry
      (DSC), and x-ray powder diffraction studies. Four salts of GW1818, the phosphate,
      succinate, mesylate, and hydrochloride, were crystalline and demonstrated
      adequate solubility. These were selected for further evaluation. Adequate
      solubility was also observed in the case of citrate and tartrate salts, but these
      were considered only as potential backup candidates because they were difficult
      to crystallize. The results of the in situ salt screening experiments also led to
      the development of an IV formulation for use in pilot toxicological studies and
      pharmacological studies. In conclusion, the in situ salt screening technique
      offers a time- and compound-conserving approach for prioritizing salt selection
      and for providing solubility and stability information useful for formulation
      development both in the research and the development stages.

PMID- 9653760
TI  - Casein hydrolysate as a rapid and/or enteric dissolving additive for oral drugs.
AB  - Two types of casein hydrolysates, casein A (mean peptide length 3.3) and casein B
      (mean peptide length 17.4) were prepared by the enzymatic hydrolysis of casein,
      and their effects on in vitro dissolution rates and oral bioavailability of drugs
      were evaluated. The in vitro dissolution behavior of the kneaded mixture of three
      drugs (diclofenac acid, diazepam, and prednisolone) with caseins A and B were
      significantly improved compared to the drugs alone, even at 1:1 weight ratio of
      drug and casein hydrolysate, even though casein A and casein B did not interact
      with drug molecules in the kneaded mixture. Only diclofenac, an acidic drug,
      showed an increased dissolution rate with added casein hydrolysates, and a more
      rapid dissolution with casein A than with casein B was observed. When the
      dissolution of prednisolone from kneaded mixture was compared at pH 1.2 and 6.8,
      the dissolution rate of prednisolone from the casein A kneaded mixture was
      considerably higher than that of prednisolone powder at both pHs, and the rate
      from the casein B kneaded mixture was higher only at pH 6.8. The plasma
      concentration-time profile showed that prednisolone was completely and rapidly
      absorbed from the casein A kneaded mixture as well as the prednisolone solution.
      In addition, prednisolone in the kneaded mixture with casein B was more difficult
      to absorb up to 1 hr after administration in comparison to prednisolone powder.
      The slow and lowered absorption of prednisolone by casein B might be explained by
      conversion of casein B to a shorter soluble peptide in the gastrointestinal tract
      and by the slow dissolution of prednisolone at acidic conditions. The
      toxicological tests revealed that casein hydrolysate is a safe drug carrier.
      Consequently, casein hydrolysates might be safely used to control the dissolution
      rate and bioavailability of a variety of drugs, depending on the peptide length
      of the casein fragments.

PMID- 9653761
TI  - Characterization of the sucrose/glycine/water system by differential scanning
      calorimetry and freeze-drying microscopy.
AB  - The objective of this study was to characterize the thermal properties of systems
      containing various ratios of amorphous and crystalline components using both
      differential scanning calorimetry (DSC) and freeze-drying microscopy. The
      glycine/sucrose system was used as a model system, since it is routinely used in
      protein formulations. DSC analysis revealed that the addition of glycine to
      sucrose solutions resulted in a decrease in the glass transition (T'g) of the
      system. The T'g of a pure sucrose solution (7% w/v) decreased from -32.3 to -51.5
      degrees C for a mixture containing a sucrose/glycine ratio of 2:5. The glass
      transition of the sucrose/glycine mixture decreased linearly as more glycine was
      added to the system. This decrease in glass transition resulted in severe
      collapse during freeze-drying of these mixtures above T'g. However, collapse was
      not observed during freeze-drying if the DSC thermogram of the sucrose/glycine
      mixture exhibited a transition resulting from recrystallization of the amorphous
      glycine. Mixtures having a sucrose/glycine ratio of 3:4 and 2:5 had a glass
      transition of -48 degrees C and -51.5 degrees C, respectively. Despite their low
      glass transition temperatures, these samples freeze-dried readily at a product
      temperature > T'g using a fast freeze-drying cycle (primary drying at a shelf
      temperature of +20 degrees C and chamber pressure of 100 mTorr) without any sign
      of collapse. The crystallization of the amorphous glycine from the frozen mixture
      of sucrose and glycine provided support during freeze-drying which prevented the
      macroscopic collapse of the final product. Freeze-drying microscopy visually
      revealed the crystallization and allowed for prediction of cake quality upon
      lyophilization. Although the freeze-drying microscope is not as sensitive as the
      DSC in detecting all transitions (it cannot detect a glass transition), it
      clarifies the interpretation of DSC, and together they provide valuable
      information regarding the relevance of each of the transitions to the final
      freeze-dried product elegance.

PMID- 9653762
TI  - Kinetic modeling for macromolecule loading into crosslinked polyacrylamide
      hydrogel matrix by swelling.
AB  - A kinetic model was proposed to characterize the swelling phenomenon of
      polyacrylamide hydrogel and to quantify and predict the loading of insulin into
      the hydrogel by swelling. Polyacrylamide hydrogel and porcine insulin were used
      in the study. During swelling, the insulin concentration in the hydrogel was
      found to be higher than that in the loading solution, which could be attributed
      to ionization of the ionic networks, Donnan exclusion, and the possible ionic
      interactions between the anionic carboxylic pendants and cationic insulin. The
      experimental results demonstrated that the proposed kinetic model was able to
      describe the swelling kinetics of polyacrylamide hydrogel and the loading
      kinetics of insulin by using only two constants [input rate (Kin) and output rate
      (Kout)]. The experimental values of Kin and Kout were found to highly depend on
      the concentration of HCl. As medium pH declined (because of the addition of HCl),
      the degree of swelling decreased and the insulin loading amount in the hydrogel
      was reduced. A linear log-log function was observed between Kin and the volume
      fraction of HCl. The Kout values also decreased with the addition of HCl, but
      remained constant after more than 1% (v/v) of HCl (0.01 N) was added. The
      proposed model was able to characterize the swelling kinetics of polyacrylamide
      and predict the loading dose of insulin in the polyacrylamide hydrogel by
      swelling.

PMID- 9653763
TI  - Effect of fabrication technique on the erosion characteristics of polyanhydride
      matrices.
AB  - The aim of this study was to investigate the effect of device fabrication
      technique on the erosion characteristics of poly[1,3-bis(p-carboxyphenoxy)
      propane:sebacic acid] [p(CPP:SA)] 20:80 copolymer. Devices were prepared using
      melt-molding, solvent-casting, and compression-molding techniques and their
      erosion was followed by determining changes in device morphology, molecular
      weight, water uptake, mass loss, and release of monomers, with time of immersion
      in phosphate buffer pH 7.4 at 37 degrees C. Melt-molded devices had a very dense
      and uniform structure and displayed characteristics typical of surface eroding
      systems. Devices produced using a solvent-casting technique had a very porous
      structure with no detectable erosion zone and the erosion profiles were
      indicative of bulk rather than pure surface erosion. Compression-molded devices
      had a dense structure and revealed a faster rate of erosion than melt-molded
      devices. A comparison of the extent of changes of polymer molecular weight, water
      uptake, mass loss, and monomer release showed a marked dependence on the method
      of fabrication.

PMID- 9653764
TI  - Introduction of dissolution error as a result of different openings in vessel
      covers.
AB  - Vessel covers are required in dissolution studies to retard solvent evaporation.
      Sufficient openings on the cover are required by the current United States
      Pharmacopeia (USP) "to allow ready insertion of a thermometer and for withdrawal
      of specimens/samples." However, the area of the opening has not been regulated by
      the USP. The purpose of this work was to measure the loss of the dissolution
      solvent as a result of openings in vessel covers and to investigate errors caused
      by the solvent loss. The method used in the study involved measurements of the
      opening areas in three commercial vessel covers and determinations of solvent
      loss under a typical dissolution condition. The results showed that the openings
      in the three covers varied from 75 mm2 to 2285 mm2; this was 1-30% of the total
      vessel open area for a USP standard vessel. The volume of the dissolution solvent
      was reduced by 0.6-3.4% for an 8-hr dissolution study, and 1.7-9.7% for a 24-hr
      study when the three different vessel covers were used. The rate of solvent loss
      exhibited a linear relationship with the area of the opening in the covers. A
      slower rate of reduction was found for a smaller initial volume of the solvent.
      The conclusion was that higher dissolution results were produced if the solvent
      loss was not considered.

PMID- 9653765
TI  - Stabilization of dichloromethane-induced protein denaturation during
      microencapsulation.
AB  - This paper describes the denaturation of protein drugs by dichloromethane (DCM)
      during the primary emulsification step of the microencapsulation process using
      biodegradable polymer matrix for controlled-release application. It was found
      that interaction of proteins such as tetanus toxoid (TT), diphtheria toxoid (DT),
      ovine growth hormone (oGH), and human chorionic gonadotropin-based antifertility
      vaccine (beta-hCG-TT) with DCM during primary emulsification stages of particle
      formulation led to the precipitation of the proteins at the aqueous organic
      interface with concomitant reduction in their immunoreactivity. On the other
      hand, the B subunit of E. coli enterotoxin (LTB) was found to be comparatively
      stable toward the denaturing action of DCM. Attempts were made to overcome the
      DCM-induced denaturation by incorporation of stabilizers during the primary
      emulsification step of the particle formulation. Of the many additives tested to
      overcome the DCM-induced denaturation of proteins, serum albumins and polyvinyl
      alcohol (PVA) showed promising results in terms of retention of the
      immunoreactivity of the protein. TT stabilized by the incorporation of serum
      albumin during the primary emulsification step not only showed immunoreactivity
      in vitro, but also invoked antibody titers in rats comparable to those obtained
      for the native protein molecules. Incorporation of 2.5% of serum albumins in the
      internal aqueous phase not only protected the protein from the degradative action
      of DCM but also led to stabilized primary emulsion, which is necessary for
      uniform entrapment of protein drugs in the polymer matrix.

PMID- 9653766
TI  - Effects of prostaglandin E1 metabolites on the induction of arterial
      thromboresistance.
AB  - Prostaglandin (PG) E1 has been shown to induce arterial thromboresistance in
      experimental animals and in man. It is known to be degraded in vivo to
      metabolites which have comparable (13,14-dihydro-PGE1) or no (15-keto-PGE1, 15
      keto-13,14-dihydro-PGE1) biological activity. It was the goal of this study to
      examine whether 13,14-dihydro-PGE1 and its derivatives might share biological
      activity in rendering the arterial wall less thrombogenic. Using a cross
      perfusion technique the aorta and iliac artery surface were exposed to a donor
      rabbits' blood. We examined the intact endothelial lining and a surface which had
      been deendothelialized before by means of a Fogarty catheter. Donor animals
      and/or receiver animals were treated daily for 1 week with 13,14-dihydro-PGE1,
      PGE1, 15-keto-PGE1, 15-keto-13,14-dihydro-PGE1, or the vehicle only,
      respectively. From the group of the receiver animals, a subgroup of 6 animals
      each was treated for the same period of time with either 13,14-dihydro-PGE1,
      PGE1, 15-keto-PGE1, 15-keto-13,14-dihydro-PGE1, or the vehicle. Immediately after
      the last administration of the respective PG or solvent, native blood from a
      donor rabbit was circulated [30 mL/min. under in vivo flow conditions (60 Hz)]
      over an arterial segment of a receiver animal. Deposition of 111Indium-oxine
      labeled autologous platelets per surface unit was quantitatively assessed. In
      vitro perfusion data were morphometrically analysed. In animals pretreated with
      13,14-dihydro-PGE1 the thromboresistance was almost comparable to that achieved
      with PGE1. In contrast, pretreatment of the donor animals (platelet) had only
      minor effects on the thromboresistance. The other compounds showed no effects. In
      vitro perfusion of human saphenous vein segments revealed PGE1 and 13,14-dihydro
      PGE1 again to be of comparable potency, while 15-keto-PGE1 and 15-keto-13,14
      dihydro-PGE1 were only active at concentrations being several orders of magnitude
      higher. Not only PGE1 but also its in vivo formed metabolite PGE0 may play an
      important role in inducing improvement of haemostatic balance via the vascular
      wall rather than the platelets. The other metabolites, however, are unlikely to
      exhibit an effect at biologically relevant concentrations.

PMID- 9653767
TI  - Role of nitric oxide in gonadotropin-releasing hormone-dependent prostaglandin F2
      alpha synthesis by frog (Rana esculenta) interrenal gland during post
      reproduction.
AB  - The aim of this study was to clarify the possible involvement of nitric oxide
      (NO) on prostaglandin (PG) E2-9-ketoreductase activity in the gonadotropin
      releasing hormone (GnRH)-dependent PGF2 alpha synthesis by the interrenal gland
      of the female water frog, Rana esculenta, during the post-reproduction.
      Interrenal glands were incubated in vitro with GnRH, NO donor (sodium
      nitroprusside, SNP), and inhibitors of phospholipase C (compound 48/80), inositol
      triphosphate (decavanadate), calmodulin (calmidazolium), NO synthase (L-NAME),
      and PGE2-9-ketoreductase (palmitic acid). Production of PGE2 and PGF2 alpha and
      NO synthase and PGE2-9-ketoreductase activities were determined. GnRH and SNP
      increased PGF2 alpha production and PGE2-9-ketoreductase activity, and decreased
      production of PGE2 and GnRH increased NO synthase activity. GnRH effects were
      blocked by all inhibitors, except for palmitic acid, which did not affect NO
      synthase activity, which is increased by GnRH. This study indicates that NO may
      be involved in regulation of the R. esculenta post-reproduction through
      stimulation of PGE2-9-ketoreductase activity in GnRH-dependent PGF2 alpha
      synthesis by the frog interrenal gland.

PMID- 9653768
TI  - Docosahexaenoic acid reduces both cyclic nucleotide and melatonin synthesis in
      rat pinealocytes.
AB  - The effect of docosahexaenoic acid (22:6n-3) on melatonin (MT) production in rat
      pinealocytes was measured. In pinealocytes, supplementation with 50 microM 22:6n
      3 for 48 h decreased MT production after a norepinephrine (NE)-stimulation (1 and
      10 microM). Using co-treatment with IBMX (1 mM), a cyclic nucleotide
      phosphodiesterase inhibitor known to increase NE-stimulated cAMP and prazosin (1
      microM), an alpha 1 antagonist, the results indicate that a) 22:6n-3 did not act
      on cyclic nucleotide phosphodiesterase activities to decrease both cAMP (-64%)
      and cGMP (-45%) levels and b) the inhibition of cGMP was higher (-70%) in
      presence of prazosin. These results confirm that in rat pinealocytes the lowering
      effect of 22:6n-3 supplementation on cAMP is likely to be dependent on alpha 1
      adrenoceptor modulation whereas the decrease of cGMP seems to involve other
      intracellular mechanisms. The absence of 22:6n-3 effect on serotonin metabolites
      suggest that the lowering effect on MT may be also correlated with alterations of
      O-methylation step.

PMID- 9653769
TI  - Immunoaffinity resin for purification of urinary leukotriene E4.
AB  - Urinary leukotriene E4 (LTE4) has been used as an index of total leukotriene
      synthesis. A wide variety of methods have been applied to measure LTE4 which has
      made direct comparison of urinary levels reported by different laboratories
      difficult. A new peptidoleukotriene immunoaffinity resin was utilized for urinary
      LTE4 purification in a method that is easy and inexpensive, utilizing
      commercially available reagents. This method is described and compared to other
      methods. LTE4 (50-250 pg/mL) added to a urine extract was quantitatively
      recovered using the immunoaffinity resin. Similarly, LTE4 (50-400 pg/mL) added to
      urine was recovered between 63 and 76%. The coefficient of variation of samples
      purified and quantified on the same or on different days ranged from 8-10%. There
      was a strong correlation (r2 = 0.95) between LTE4 concentrations determined after
      immunofiltration and immunoaffinity purification. Although there was a good
      correlation between urinary LTE4 levels measured without purification compared to
      after immunoaffinity purification, the high y-intercept of 179 indicates the
      presence of interfering substances in unpurified urine. Urinary LTE4 in normal
      healthy adults was 80 +/- 7 pg/mg creatinine, similar to that previously reported
      following HPLC or immunofiltration purification. Urinary LTE4 was also measured
      in healthy children (age 3-12) and found to be 103 +/- 9.

PMID- 9653770
TI  - Expression of platelet-activating factor receptor transcript-2 is induced by
      shear stress in HUVEC.
AB  - Platelet-activating factor (PAF) is an important lipid involved in inflammation
      reaction and circulation regulation. The receptor for human PAF is synthesized
      from two spliced transcripts of the same gene. Our observation in the present
      study shows that HUVEC express transcript-1 only in the static condition. Shear
      stress induces the expression of transcript-2 in these cells but not transcript
      1, resulting in increased PAF receptor expression as measured by FACS analysis.
      These results suggest that shear stress may increase the susceptibility of
      endothelial cells to PAF by inducing transcript-2 expression.

PMID- 9653771
TI  - Cationic lipids (lipofectamine) and disturbance of cellular cholesterol and
      sphingomyelin distribution modulates gamma-secretase activity within amyloid
      precursor protein in vitro.
AB  - To study beta-amyloid protein generation we expressed different amyloid precursor
      protein (APP) isoforms in the human neuroblastoma cell line SY5Y (for details see
      (1)). Treatment with lipofectamine, an cationic lipid for eucaryotic cell
      transfection, inhibits gamma-secretase activity and stimulates the physiological
      APP cleavage by alpha-secretase activity. Beside the MDL inhibitor (2), this is
      the second agent that shows modulation of gamma-secretase activity in vitro.
      Further, we show that disturbance of cellular cholesterol and sphingomyelin
      distribution in transfected SY5Y cells results in an overproduction of beta
      amyloid protein. This provides experimental evidence that membrane instability
      influenced the proteolytic activity of gamma-secretase within the APP molecule.

PMID- 9653772
TI  - Differing profiles of prostaglandin formation inhibition between selective
      prostaglandin H synthase-2 inhibitors and conventional NSAIDs in inflammatory and
      non-inflammatory sites of the rat.
AB  - The present study examined the inhibitory profiles of NS-398 and nimesulide
      against prostaglandin (PG) formation in inflammatory and non-inflammatory sites,
      and compared them with those of aspirin and indomethacin. In vitro, indomethacin
      inhibited PGH synthase (PGHS)-1 and PGHS-2 almost equally, while NS-398 and
      nimesulide inhibited only PGHS-2. NS-398 (1, 10 mg/kg) and nimesulide (3 mg/kg)
      slowed the rate of plasma exudation and thus the exudate accumulation in rat
      carrageenin-induced pleurisy. Aspirin (30, 100 mg/kg) and indomethacin (10 mg/kg)
      also reduced this rate. NS-398 and nimesulide reduced the PGE2 more potently than
      TXB2 and 6-keto-PGF1 alpha in the exudate. However, aspirin and indomethacin did
      not exhibit this selectivity. The levels of PGE2 correlated significantly with
      the plasma exudation rate. Moreover, nimesulide (3 mg/kg) did not affect PGE2
      formation in rat stomachs injected with 1 M NaCl solution, while indomethacin (10
      mg/kg) reduced it. Thus, NS-398 and nimesulide exhibit different inhibitory
      profiles from aspirin and indomethacin against PG formation. These results
      suggest that PGE2 may be produced by PGHS-2 in the inflammatory site, and may
      play a more prominent role than PGI2 in plasma exudation.

PMID- 9653773
TI  - Effects of luteinizing hormone (LH), PGE2, 8-Epi-PGE1, 8-Epi-PGF2 alpha,
      trichosanthin and pregnancy specific protein B (PSPB) on secretion of
      prostaglandin (PG) E (PGE) or F2 alpha (PGF2 alpha) in vitro by corpora lutea
      (CL) from nonpregnant and pregnant cows.
AB  - Both Day 14 corpora lutea (CL) of the estrous cycle and Day 200 CL of pregnancy
      secrete detectable prostaglandin E (PGE) and prostaglandin F2 alpha (PGF2 alpha)
      in vitro. Corpora lutea from Day 200 pregnant cows secrete more PGE and PGF alpha
      in vitro than Day 14 CL of the estrous cycle when incubated in control medium
      without treatments (p < or = 0.05). In addition, secretion of both PGE and PGF2
      alpha in vitro by both Day 200 CL of pregnancy and Day 14 of the estrous cycle
      increase (p < or = 0.05) with time in culture in the absence of treatments. The
      PGE:PGF2 alpha ratio secreted at 4 h in the absence of treatments by Day 14 CL of
      the estrous cycle was 1.2 and at 8 h was 1.0 and did not differ (p > or = 0.05),
      while the PGE:PGF2 alpha ratio secreted by 200 day CL of pregnancy in the absence
      of treatments at 4 h was 0.8 and at 8 h decreased (p < or = 0.05) to 0.4. The
      PGE:PGF2 alpha ratio at 8 h by 200 day CL of pregnancy was lower (p < or = 0.05)
      than in the Day 14 CL of the estrous cycle at 4 or 8 h. Secretion of PGE or PGF2
      alpha was affected by luteinizing hormone, PGE2, 8-Epi-PGE1, 8-Epi-PGE2,
      trichosanthin, and pregnancy specific protein B (PSPB) and was time and dose
      dependent (p < or = 0.05). In summary, the altered ratio of PGE:PGF2 alpha may
      explain the decreased secretion of progesterone at 8 h by Day 200 CL of pregnancy
      reported previously from the same samples. In addition, caution should be
      exercised in interpretation of progesterone secretion data with bovine CL studies
      in vitro. Also, PSPB may play an indirect role through PGE to regulate bovine
      luteal secretion of progesterone.

PMID- 9653774
TI  - Inhibition of Na+,K(+)-ATPase by platelet-activating factor in dog submandibular
      glands.
AB  - Physiological stimulation of dog submandibular gland has been shown to generate
      platelet-activating factor (PAF). However, PAF is not released from cells in the
      tissue. To assess its intracellular activity, the effect of PAF on Na+,K(+)
      ATPase was examined in dog submandibular gland cells. PAF inhibited Na+,K(+)
      ATPase in membrane preparations, and the inhibitory effect was dependent on the
      protein concentration in the enzyme preparation. The inhibitory effect of a low
      concentration of PAF was antagonized by a PAF-receptor antagonist, BN 50,739, but
      at high concentrations, PAF was not antagonized. Kinetic analysis of PAF
      inhibition of Na+,K(+)-ATPase suggests that the inhibition of Na+,K(+)-ATPase by
      PAF is not due to competition by PAF at K(+)- or Na(+)-binding sites on the
      enzyme, but by complex inhibitory mechanisms. These results suggest that PAF may
      interact with specific and nonspecific site of action resulting in the inhibition
      of Na+,K(+)-ATPase. Ouabain increased mucin release from dog submandibular gland
      cells. Because Na+,K(+)-ATPase and ion exchange pathways are important in the
      secretory responses of acinar cells, PAF may regulate intracellularly the
      secretory function of acinar cells by modulating Na+,K(+)-ATPase and ionic
      homeostasis.

PMID- 9653775
TI  - Prostanoid-induced contraction of the rabbit isolated uterus is mediated by FP
      receptors.
AB  - Natural and synthetic prostanoid agonists were used to study the prostanoid
      receptors involved in contraction of the mature, isolated uterus of virgin
      rabbits. The prostanoids elicited contractile responses with a rank order of
      potency of PGF2 alpha, fluprostenol > PGD2 > U-46,619 > PGE2 > carbaprostacyclin
      with mean EC50 (nM) values of 4, 6, 34, 550, 1318 and > 10,000, respectively.
      Carbachol, a muscarinic agonist given after the prostanoids to elicit a reference
      contraction, had a mean EC50 value of 1.1 microM. The results show that the
      mature rabbit uterus is most sensitive to prostaglandin FP agonists and, thus,
      can be defined pharmacologically as an FP receptor preparation. These findings
      may facilitative investigations into the possibility of different prostanoid
      receptor populations. In the absence of useful competitive FP receptor
      antagonists, agonist potency data is particularly useful in systems where cross
      species comparisons and tissue-related factors are not involved. The potent
      activities of the FP agonists, PGF2 alpha and fluprostenol, in the isolated
      jugular vein and uterus of the rabbit suggest that these tissues may be useful
      for intra-species comparisons.

PMID- 9653776
TI  - [Computer-assisted psychiatric rehabilitation].

PMID- 9653777
TI  - [Effectiveness of computer-assisted attention training of schizophrenic
      patients].
AB  - Recent years witnessed a considerable proliferation of computer-based training
      programmes as instruments of cognitive rehabilitation for schizophrenic patients.
      A study on the effects of a 3-week computer-based attention training with
      schizophrenic patients is presented. The Span of Apprehension and the Continuous
      Performance Test (CTP) were carried out before and after the training period.
      Performance improvements were found only on few attention training tasks.
      Schizophrenics had higher post-treatment hit rates on the Span of Apprehension,
      but no post-treatment improvements were observed in the CPT. Performance of
      trained patients in the external attention measures was not superior to
      performance of matched schizophrenic control patients. These data suggest that
      brief intensive computer-based attention remediation does not lead to enhanced
      attentional capacity in schizophrenia. Thus, it might be more adequate to teach
      behavioural strategies that bypass attention deficits or to offer programmes for
      exercising more complex cognitive skills than to try to remedy basic cognitive
      impairments.

PMID- 9653778
TI  - [Computer-assisted cognitive training of schizophrenic patients. Use of
      evaluation outcome for developing an individualized training method].
AB  - The paper deals with the evaluation of a computer-based cognitive group training
      programme for schizophrenic patients. The evaluation of the training results of
      100 patients who participated in an earlier training scheme showed ceiling
      effects in up to 46% of the cases. In the remaining cases the improvements varied
      in a wide range between 1.6 and 20%. These results implied that the training had
      to be adapted more closely to the specific needs of the individual patient. To
      this end we developed criteria for each task to decide whether training in this
      task is necessary or the performance is sufficient. This approach limits training
      to those tasks in which patients display deficits. Satisfactory improvement
      terminating training for the specific task, is defined as an increase in correct
      responses of at least 10%. For those tasks in which reaction times are used as
      performance measure, the criterion is a 10% increase in percentile rank. An
      analysis of the new training programme with the data of 20 patients revealed that
      27% of the tasks showed ceiling performance with no further training need. In the
      remaining tasks the patients' performance attained the training criterion in 68%,
      at instances mostly even after one additional session. These preliminary results
      indicate that the new training scheme is able to provide more flexibility,
      individualization and an enhanced focus on the patients' deficits.

PMID- 9653779
TI  - [Computer-assisted neuropsychological training in neurological rehabilitation].
AB  - Using computer-assisted cognitive training to treat patients with cognitive
      disorders has proved a useful tool in neurological rehabilitation. This has been
      shown by positive experience in many rehabilitation clinics but also in numerous
      control studies investigating the efficiency of such training. Patients with
      attention deficits show the most pronounced improvements as the computer with its
      technical possibilities is an ideal training instrument because of stimulus
      representation and reaction time measures. In other areas, computer training has
      become an essential therapeutic means complementing other therapies. In a
      clinical environment it seems that computer training is essential because it
      enables attaining the necessary therapeutic density. However, training must be
      integrated and become part of a global therapeutic framework.

PMID- 9653780
TI  - [Computer-assisted training in genetically-induced neuropsychological deficits. A
      case report of a patient with de Grouchy syndrome I (chromosome 18 p syndrome)].
AB  - The present case study is a report on computer-based training approach in a male
      patient suffering from the de-Grouchy syndrome I (with a characteristic
      chromosomal deletion pattern), who along with psychotic symptoms displayed
      neuropsychological deficits. Participating in a well-established intervention
      programme aimed at a broad spectrum of psychological functions, the patient went
      through 36 training sessions. With regard to outcome assessments one focus was on
      improved performance in the training tasks, while the other one referred to
      transfer effects, as indexed by a neuropsychological test battery which was given
      before and after the entire programme. In both areas substantial gains from
      training emerged according to the collected data. In view of these results
      neuropsychological training approaches appear to have a perspective even in
      behavioural deficits with a genetic basis.

PMID- 9653781
TI  - [Psychotropic drugs in pregnancy: uses and risks].
AB  - To reduce insecurities concerning the pros and cons of psychopharmacological
      treatment of mental disorders during pregnancy, recent papers on teratogenic
      risks of different (groups of) drugs, and on therapeutic strategies of psychiatry
      disorders were reviewed and the results summarised. Psychotropic medication
      sometimes increases the risk of congenital malformations. It may cause peripartal
      toxicity and neurobehavioral changes; on the other hand, these risks have to be
      weighted against the proven benefits of the drugs. Untreated mental disorders
      seriously endanger the offspring during pregnancy and after delivery, and hence
      psychopharmacological treatment may be advisable in spite of the risks involved.

PMID- 9653782
TI  - [Children of mentally ill parents. A study of problem awareness in clinical
      routine practice].
AB  - The risk of developing clinically relevant psychiatric disorders in the lifetime
      course is significantly greater among children of mentally ill parents. A child
      adapted programme of information concerning the nature and symptomatology of
      parental illness is considered to be an important preventive factor, and lies
      within the domain of the psychiatrist's or therapist's responsibilities. During
      the developmental phase of a prevention project at Freiburg University's
      Department of Psychiatry and Psychotherapy, both clinical practice and the level
      of problem awareness among patients and the therapists were evaluated. Over a
      period of one year, consecutive interviews involving 114 patients with children
      under 18 years of age, as well as their respective therapists, were conducted.
      The results showed that: scarcely any exchanges between children and therapists
      took place; the extent to which children are informed about parental illness must
      be considered as small; a high percentage of such children are already evaluated
      by their parents as disturbed, and the pressing need for support exists.

PMID- 9653783
TI  - [Suicide in depression, lost years of life and gross social consequences. What is
      the outcome of suicide prevention?].
AB  - In recent years there has been a tendency in research and clinical treatment to
      discuss also economic aspects of mental illness in the context of outcome and
      consequences of treatment for the individual and society. In our study on
      economic consequences of suicide prevention we could show that a reduction of
      suicide mortality of depressed patients could save money to the tune of thousands
      of million Deutschmark.

PMID- 9653784
TI  - [Interviewer effects in assessing subjective quality of life and satisfaction
      with care in sheltered housing].
AB  - The impact of interviewer-effects on subjective evaluative criteria was examined
      in a randomized control group design (n = 26 x 2) of clients of sheltered living
      in Berlin-Spandau. The assessment of care and subjective quality of life showed
      that clients were more satisfied if they had been interviewed by their
      responsible caregivers compared to interviewers from other providers of the same
      region--unknown to the clients. Conductibility of interviews was independent of
      interview conditions. A systematic overestimation of satisfaction should be taken
      into account if responsible caregivers interview their own clients. Such data
      should not be used comparing different settings.

PMID- 9653785
TI  - [Patient suitability for discharge from psychiatric hospitals].
AB  - OBJECTIVE: To assess the possibility of discharging psychiatric inpatients of two
      large Mental Hospitals in Lower Austria. METHODS: A point prevalence study was
      performed in 1992. Treating psychiatrists were asked to evaluate the possibility
      to discharge patients under the hypothetical assumption that a broad range of
      residential facilities were available. RESULTS: The inpatient proportion had
      decreased from 2179 in 1974 to 1032 in 1992. Of the 1992 population 75.7% might
      be discharged. Most patients (41.5%) were regarded as needing a permanently
      staffed home. CONCLUSIONS: Although the inpopulation of the two large Mental
      Hospitals studied had decreased over a period of 18 years already by over 50
      percent, the results of this study show that there is a large potential for
      further reform. Since the evaluation was carried out by the treating
      psychiatrists in the hospital, who might have been in a conflict of interests or
      might have preferred the treatment they are providing themselves, this finding is
      particularly remarkable.

PMID- 9653786
TI  - [Ecstasy and social pension: lost for life at 20 years of age?--Behavioral
      therapy of an anxiety disorder].

PMID- 9653787
TI  - [Attempted suicide in Alzheimer phobia].

PMID- 9653788
TI  - [The right for care does protect: a case].

PMID- 9653790
TI  - [Facial-oral therapy in craniocerebral diseases].
AB  - Presented are 16 patients (4 women and 12 men) of a neurological early
      rehabilitation ward with various neurological initial situations. Diagnoses range
      from traumatic brain damages to hypoxic brain lesions caused by complications
      during anaesthesia, from subarachnoid haemorrhages with consecutive
      complications, to intracerebral haemorrhages. All patients have been examined at
      the beginning by an ENT specialist and/or phoniatrically. Regarding the structure
      of the patients' complex neurological symptoms, they were all suffering from more
      or less severe impairments in the faciooral tract. At the beginning of the
      multifocal neurological rehabilitation treatment all patients had been submitted
      to dysarthrophony and/or dysphagia examination according to K. Coombes. We will
      compare results, objectives and therapeutic developments during the faciooral
      therapy including physiotherapy and ergotherapy based on the Bobath concept. We
      will further discuss the periods between occurrence of the damaging event and the
      onset of multimodular neurological rehabilitation. Further discussed is the
      influence of secondary complications on the therapeutic development and, finally,
      the clinical-social outcome of the patients.

PMID- 9653791
TI  - [The significance of urinary tract infections in patients with cerebrovascular
      diseases during clinical rehabilitation].
AB  - In 361 patients with cerebral stroke a study of medical and neurological
      complications was undertaken. Among a total of 131 complications (36.2%) a
      striking incidence of urinary tract infections was seen: 83 cases (22.9%).
      Patients without complications had an average stay of 61.2 days in hospital,
      those with urinary tract infections had 77 days (p < 0.05). In patients with
      cerebrovascular accidents voiding dysfunctions are common. Great care must be
      taken to prevent complications: indwelling catheters should be used only over
      short periods of time. In case urinary drainage is needed over a long period of
      time, suprapubic catheterization should be preferred.

PMID- 9653792
TI  - [Future occupational plans of patients after orthopedic rehabilitation: how are
      they expressed? What influences them?].
AB  - Perceptions about one's occupational future are regarded as the initial phase in
      an ongoing process of occupational resettlement towards achieving gainful
      activity. Actual gainful activity, however, tends to be increasingly dependent on
      a number of labour market variables. At the end of an orthopaedic rehabilitation
      measure, 341 patients with pain syndromes of the locomotor system were
      interviewed concerning their vocational perspectives and notions, and the data
      obtained were studied in association with anamnestic and psychosocial factors. It
      is assumed that both plain expectations (such as returning, or not returning, to
      work) and multi-layered statements alike (such as the dual message of returning
      and of not returning to work, at first glance incompatible) will frequently be
      masked in the interview. Distinct, differing patterns were nevertheless found for
      the various patient groups regarding pain description, pain course, subjective
      disablement by pain, subjective job burden, subjective well-being, rehab
      expectations, and judgement of therapy outcome. Similar differences were stated
      for the social situation, indicated inter alia by (in)capacity for work, or
      application for benefit award (severely disabled person status, invalidity
      pension). Pain drawings, pain severity scaling, differentiated description of
      various pain qualities, the Pain Disability Index, all emerged as useful and
      practical additional tools in elucidating these patterns.

PMID- 9653793
TI  - [Reliability and validity studies with the triflexometer, a new method for
      assessing form and flexibility of the spine].
AB  - Developed by Orthotronic Medizintechnik GmbH, the so-called Triflexometer,
      version 3.22 was tested for its reliability and validity in measuring spinal
      posture and mobility. Reliability studies on 20 healthy subjects have shown this
      measurement method to be reliable, yet intra- and inter-rater reliability
      analyses also revealed that even for this healthy population discrepancies in the
      various measures may occur, both due to differences in compliance as well as
      fatigue and learning effects, and due to difficulties in stabilization of the
      normal posture, to a lesser extent due to certain specifics of the measurement
      technique (placing the markers, guiding the sensor). In total spinal immobility
      (ankylosing spondylitis), practically identical measurements are found, as is the
      case in dummy studies. The validity study on 20 healthy subjects found good
      correlations between the measurements obtaining using the triflexometer and those
      for double inclinometer, respectively, and that only minor mean value differences
      occur for the two methods. Also, triflexometer measurements for total anteflexion
      were found to correlate with those determined with the fingertip-to-floor method,
      no correlation was present however between the Triflexometer values and the
      Schober test. Triflexometer measurements performed on 114 healthy subjects of
      various ages served to prove that the range of spinal movement in the directions
      measured (sagittal and frontal) will reduce with age. To a lesser extent, this
      also applies to hip movement. Overall, our findings prove the triflexometer an
      easy-to-handle system which possesses high reliability and is suitable for valid
      and objective noninvasive assessment of global and segmental spinal mobility.
      Triflexometer examinations are highly uncomplicated to implement, and print-outs
      of the results obtained permit lasting documentation of the present status.

PMID- 9653794
TI  - [Integrated occupational work capacity evaluation in medical rehabilitation-
      experiences and prospects exemplified by psychosomatic rehabilitation].
AB  - Psychosomatic rehabilitation is often initiated when lasting work disability,
      loss of job, and pension application have occurred. After a review of the
      relevance of vocational strains and of predictors for reintegration, we present a
      model of an integrated work hardening programme in Psychosomatic Rehabilitation.
      Results for 64 patients are illustrated by case vignettes. Especially when
      lasting work disability and unemployment have undermined the patients' sense of
      competence and endurance, work hardening promotes return to work, realistic self
      appraisal and vocational reorientation. The social and medical assessment and the
      coordination of vocational rehabilitation measures are improved. The
      implementation of a work hardening programme requires the provision of a variety
      of (unpaid) work opportunities, independent assessment of work performance by
      supervisors and social worker, psychological support and close cooperation with
      rehabilitation services.

PMID- 9653795
TI  - [Identification of psychologically impaired patients in cardiologic
      rehabilitation].
AB  - As psychological factors have a substantial influence on the further medical,
      psychological and occupational career of a patient with somatic disease, early
      identification of patients with psychological disturbances is of special
      importance in medical rehabilitation. The share of psychologically disturbed
      patients in a cardiac rehabilitation clinic has been screened. Different methods
      for identification of anxious and depressive patients (by medical and
      psychological staff as well as a screening instrument) are compared. Concluding,
      the benefit of introducing a screening instrument as a routine procedure is
      discussed under the aspect of effectivity.

PMID- 9653796
TI  - [Community occupational rehabilitation for women--a model project of Frankfurt am
      Main vocational guidance in Kassel].

PMID- 9653797
TI  - [Quality assurance in early neurological/neurosurgical rehabilitation. Federal
      Working Group of Medical-Occupational Rehabilitation Centers (phase II)--Working
      Group for Early Neurologic/Neurosurgical Rehabilitation].

PMID- 9653798
TI  - [Measuring the quality of life of children and adolescents with asthma--The
      Pediatric Asthma Quality of Life Questionnaire].
AB  - Quality of life becomes more and more important in evaluating the effects of
      treatments. At the moment, different questionnaires to measure quality of life in
      children and adolescents with asthma are available. The Paediatric Asthma Quality
      of Life Questionnaire (PAQL) was developed by Juniper and co-workers in Canada
      and has already been translated into German. It is a self- or interviewer
      administered instrument for children and adolescents between age 7 and 17. The
      PAQL contains 23 items in three domains: activity limitation, symptoms, and
      emotional function. The empirical results suggest that the PAQL is reliable and
      sensitive to clinical change. Problems associated with the administration are
      discussed.

PMID- 9653799
TI  - References to people in the communications of female and male youths with mental
      retardation.
AB  - Gender-related differences have consistently been reported in the language of
      adults and children with no disabilities. One well-replicated finding is that
      females discuss people and relationships more often than do males, particularly
      in conversations with other females. These stylistic variations in language are
      considered to have implications for the adaptive functioning of language users,
      most particularly females. Although studied thus far only in nondisabled
      individuals, such issues of language style use may be of equal or greater concern
      for those with mental retardation. How does a cognitive impairment intensify or
      reduce gender-linked language styles and their effects? Language transcripts were
      obtained from eight male and eight female participants with retardation,
      interacting separately with one male and one female adult partner. Half of the
      participants used speech as their primary mode of communication: the others
      relied on vocalization, gesture, or augmented modes. Participants using speech
      showed gender-linked language patterns similar to nondisabled individuals, with
      females discussing people significantly more often than males. Females using
      nonspeech modes, in contrast, showed a severe reduction in person-referencing
      that was not accountable by their expressive speech limitations.

PMID- 9653800
TI  - Implementation and effectiveness of a home-based early intervention program for
      blind infants and preschoolers.
AB  - This article presents results from a comprehensive evaluation of a home-based
      early intervention project for congenitally blind young children. Five full-term
      and five preterm blind children, who had a mean age of 12 months at the beginning
      of the project, were visited at home with their families every 2 weeks over a 2
      year period. Results showed that an individualized, handicap-specific early
      intervention using different types of parent involvement (cotherapist, parent
      counseling) could be implemented successfully. Compared with controls,
      developmental test data from the ages of 12 to 36 months showed an accelerating
      impact on the full-term children. However, no intervention effects could be found
      in the preterm children. This finding was mainly due to methodological
      limitations (e.g., selection bias). The best results among full-term children
      were found on blindness-specific scales (e.g., orientation and mobility). It is
      concluded that the outcomes in full-term children confirm the success of this
      type of early intervention.

PMID- 9653801
TI  - Perception of service needs by parents with intellectual disability, their
      significant others and their service workers.
AB  - It is well recognized in the literature that parents with intellectual disability
      require support and social services. There is growing interest in these services
      being responsive to parent-identified concerns, particularly as it has been
      suggested that parents' concerns may differ from those reported by service
      workers, family members, or friends. In the Australian study reported here, the
      views of parents with intellectual disability, their significant others and
      service workers were sought on parents' service needs on 20 items incorporating
      child care, social and community living, and domestic skills. There were
      significant differences in the perceptions of the parents, workers, and
      significant others on the help parents needed. Several gaps in services were also
      identified. From the parents' perspective, their greatest unmet needs were in the
      community participation area, specifically with help to explore work options, to
      know what community services are available and how to access these, and to meet
      people and make friends.

PMID- 9653802
TI  - Resident behaviors and characteristics as determinants of quality of residential
      care: an observational study.
AB  - The effects of resident behaviors and resident characteristics on the quantity
      and quality of care they receive from direct-care staff was examined. Four
      hundred and fifty-two residents with severe and profound mental retardation and
      416 direct care staff members were involved. Naturalistic observations were
      conducted on direct-care staff behavior, that is, staff-resident initiatives,
      staff affection, staff communicative behavior, on resident behaviors (i.e.,
      maladaptive, stereotypic, and adaptive behavior, position, attending, and
      communicative behavior), and on resident characteristics (i.e., gender, age,
      ambulancy, sensory handicaps, and seizure disorder). By importance, residents'
      ambulancy/motoric skills, their communicative behavior, and attending behavior
      accounted for the greatest differences in the quality and quantity of the care
      they receive from direct-care staff. Given that certain resident characteristics
      can be ameliorated through training, residents themselves may control, to a
      certain extent, the care they receive from direct-care staff in residential
      facilities.

PMID- 9653803
TI  - Attention deficit hyperactivity disorder among adults with severe and profound
      mental retardation.
AB  - The present study investigated the incidence of attention deficit hyperactivity
      disorder in a sample of 86 adults with severe to profound mental retardation.
      Participants were evaluated by supervisory staff using the diagnostic criteria
      from the Diagnostic and Statistical Manual of Mental Disorders (American
      Psychiatric Association, 1994) and Conners' (1990) Hyperactivity Index. Using the
      most conservative measure, 15% of the sample met the diagnostic criteria. This
      measure was not influenced by the subjects' chronological age, adaptive age, IQ,
      or gender. Implications of this finding for continued research and practice were
      discussed.

PMID- 9653804
TI  - The effects of biological and social risk factors on special education placement:
      birth weight and maternal education as an example.
AB  - The effects of birth weight (BW) and maternal education (ME) on special education
      placement at age 10 were studied. Epidemiologic methods quantified risk to the
      individual and to the population using an electronically linked, county-wide
      database of birth and school records. A dose-response relationship was found
      between BW and ME. High ME may serve as a buffer for children with a biological
      risk for developmental delays. A clinically important finding was that children
      born with very low BW to mothers with low ME were at a high level of individual
      risk for receiving special education services. However, such children accounted
      for a small number of the overall cases. The largest percentage of children
      receiving special education services had the single risk factor of low ME. From a
      public policy standpoint, children born to mothers with low levels of education
      are an important group to target for early intervention.

PMID- 9653805
TI  - The sources of variation in the human genome and genome instability in human
      cancers.
AB  - The human genome is viewed as a stable collection of about 60,000-70,000 genes--a
      minority of protein--coding DNA sequences--dispersed in a large majority of
      noncoding DNA sequences--more than 90 per cent of the entire genome sequences.
      Some of these ubiquitous noncoding DNA sequences, metonymically called "parasitic
      DNA," "ballast DNA," "selfish DNA" or "extra DNA," especially, the repeated
      sequences tandemly organized, are not stable but vary with considerable
      frequency. Recently, the confused or inadequately known origin of native of
      pathological variations of these DNA sequences appears to be unravelled, with
      great implications in genome stability. The human chromosomes, the bearer of
      genome, store and carry it. Their structure is qualified to perform its
      fastidious functions. The chromosomal conformation, "with variable geometry,"
      exposed to genetoxic action of different damaging factors and to torsional stress
      after their fast and repeated changes during mitosis. The exaggerate exceeding of
      the native variation of human genome in disease states, probably, generates
      genome instability. The chromosome fragility--the cellular phenotypic expression
      of these molecular instability--reflects the closely relations between the genome
      and its carrier. The pattern of DNA replication with asynchrony of different
      domains of "parcelled" genome and the results of replication, susceptible to be
      corrected by the action of DNA repair genes, render certain limited regions of
      genome more vulnerable to damaging. These "target" regions focused damaging
      effects and exhibit an increased susceptibility to breakage and recombination,
      often with chromosomal expression. The coincidence of these regions, frequently,
      with locations of many protooncogenes and sometimes, antioncogenes could be
      subsequently, starting points for a genuine chain of genomic events related to
      growth cell and cell division. Cancer multistage accumulation of various genomic
      disorders in a single cell tends to take advantage of discriminating situations
      of these regions, which themselves can generate other genetic disorders,
      involving its in carcinogenesis. The gene expression disorders or the genuine
      mutations of dominant protooncogenes and the recessive behaviour of antioncogenes
      explain the nature of human cancers--a mixture of inherited and somatically
      acquired gene disorders. They attest the recessive characteristic of human cell
      malignancy and emphasize the decisive role of cancer predisposition which
      operates in interaction with damaging environmental factors. Seemingly, the
      pivotal causes of genome instability originate from strange behaviour of certain
      repeated DNA sequences dispersed throughout the human genome. Perhaps they hold
      the key to the puzzle of cancer processes.

PMID- 9653806
TI  - Possible involvement of L-arginine-nitric oxide pathway in the modulation of
      stress-induced analgesia.
AB  - The possible participation of NO in the pain modulation and stress analgesia was
      studied in Wistar adult rats. Cerebral citruline as a stoichiometric coproduct of
      NO from L-arginine increased from the mean value 5.6 +/- 0.4 nM/mg.Pt. to 8.9 +/-
      0.5 nM/mg.Pt. in acute immobilization stress. Intraperitoneal administration of L
      arginine caused only in high doses (50 mg/kg body weight) a small transient
      decrease of tail-flick latencies to the thermoalgesic stimulus, without
      significant changes of the stress analgesia induced by the restraint stress. In
      the pretreated animals with L-NAME a progressive increase of latency time was
      obtained and the increased latencies induced by acute immobilization appeared
      significantly potentiated. These results offer new indirect evidence in favour of
      the modulatory role of NO in the thermoalgesic sensitivity and stress induced
      analgesia.

PMID- 9653807
TI  - The renin-angiotensin system and the effect of propranolol upon the cerebral
      cortical and hypothalamic circulation in hypoxia.
AB  - The regulatory mechanisms of the cerebral blood flow have preoccupied the
      physiology department of Cluj since the end of the 4th decade. These studies
      continued over the last years. The researches progressed from the studies of
      regulation by blood pressure changes to the nervous regulation and to the
      metabolic one. This paper's subject is the renin-angiotensin and adrenalin system
      influence on the changes of cerebral blood flow during the general hypoxic
      hypoxia and cephalic ischemia. Experiments were performed in 10 dogs
      anaesthetised with a mixture of chloralose, urethan and morphine. Hypoxic hypoxia
      was obtained by breathing a mixture of 11% oxygen in nitrogen, in a closed system
      and cerebral ischemic hypoxia by partial compression of the carotid arteries,
      after the ligation of the vertebral and thyroid arteries. The arterial blood
      pressure and the cerebral and hypothalamic blood flow, measured with the heated
      thermoelement, were registered. The plasma renin activity was tested
      radioimmunologically before, at 1.5 min, 5, 10 and 15 min, after the beginning of
      hypoxia. In ischemic hypoxia the experiment was repeated after venous perfusion
      with propranolol (0.6 mg/kg/h). The systemic blood pressure increased in both
      forms of hypoxia. The cortical and hypothalamic blood flow increased with the
      systemic arterial blood pressure. The hypothalamic blood flow remained stable or
      diminished a little. Propranolol increased the cerebral blood flow during
      ischemic hypoxia up to 300%. The i.v. administration of angiotensin (1-5 mg/kg)
      increased the cortical flow, while the hypothalamic flow remained self-regulated.
      Plasma renin activity increased more in general hypoxic hypoxia, than in cephalic
      ischemic hypoxia. After propranolol the increase was higher in this hypoxia.
      Propranolol produced a major activation of the renin-angiotensin system and of
      the cortical blood flow in ischemic cephalic hypoxia, the renin-angiotensin
      system being located in the cerebral structure. As well high doses of angiotensin
      produced cerebral vasodilatation in small cerebral vessels. This effect was found
      in our experiments in the cortical blood flow too. Our results indicate a
      beneficial propranolol effect on cortical circulation in ischemic hypoxia.

PMID- 9653808
TI  - Heart ultrastructure in experimental acute pancreatitis.
AB  - Acute pancreatitis reproduced on white rats provoked following modifications of
      myocardium ultrastructure: 1. Affection of the microcirculation vessels
      structure, what induce interstitial edema and cardiomyocytes hypoxia. 2. The
      cells appearance of a rough type with the overcontracted myofibrils making up,
      probably occurs as a result of supercharging with calcium can be caused by
      deficiencies in the sarcolemma structure. 3. The intracellular edema of the
      cardiomyocytes and their supercharging with calcium can be caused by deficiencies
      in the sarcoma structure. 4. In the latest periods, the cardiomyocytes and the
      connective tissue reactions to the lesion is represented of compensatory
      hypertrophy of the cardiomyocytes and collagenizing the myocardium stroma.

PMID- 9653809
TI  - O.H.--a strong slow wave sleep inducing factor in tortoise (Emys orbicularis).
AB  - The paper would be a contribution to the very complex and not yet clarified field
      of neurochemistry of slow wave sleep (SWS). The study was performed on 30
      tortoises (Emys orbicularis): 20 "donors" and 10 "receivers". The animals were
      equipped with chronic cannula inserted in the third ventricular space and
      electrodes for electrographic recording (EEG, EOG, EMG and ECG). The controls
      consisted in administration into the third ventricle of receivers of 30
      microliters of saline or concentrated cerebro-spinal fluid (CSF) extracts from
      awake donors. The results were negative, i.e. the injected tortoises conserved
      their waking state indefinitely. The experiments were performed by introduction
      of 30 microliters of concentrated CSF extracts obtained from asleep donors into
      the third ventricular space of receivers. All the animals presented the
      behavioural and electrographic signs of the physiological SWS. The logical
      conclusion is that in the development of reptilian SWS, an endogenous SWS
      inducing factor, which I called "O.H." (orbicularis hormone), was secreted by
      some hypnogenic structures and discharged in the CSF, with the consequences
      presented above.

PMID- 9653810
TI  - Visual processing of configuration-dependent spatial characteristics of shapes
      and patterns. A model useful in the study of the role of the departure from
      circularity or dispersion of shapes in human visual perception.
AB  - In this work a theoretical model was used in combination with testings on normal
      subjects to get more insight in the role of the departure from circularity or
      dispersion of the shapes in visual perception. The model was inspired by the
      observation that the intensity of the effect of a given level of contrast of a
      shape usually increases, for the same area, with the shape being better
      concentrated around a center. The model introduces as a measurable characteristic
      the degree of concentration or dispersion of a shape with respect to a center.
      The measure was based on the maximum of the convolution integral of the
      characteristic function of the shape with the weighting function 1/2 pi r, r
      being the distance between the point of convolution and the surface element to be
      integrated. A program for the calculation of the degree of concentration of
      figures and other related processing operations was developed in Turbo Pascal
      language on a 486 PC. The program included the possibility to generate various
      figures and to operate on them various transformations such as strangulation,
      fragmentation with separation of fragments. The model introduces a center of the
      figure, the point best surrounded by the whole figure, with a geometric and
      visual significance, as resulting from the good concordance between its
      calculated and perceived positioning in different relatively simple shapes. In
      symmetrical compact figures subjected to a central separation or narrowing two
      centres appear entering the two resulting nuclear parts; a good concordance
      between model and perception was again observed in this transition to two centres
      and their subsequent positions in the two nuclear parts. In accord to model
      prediction, testings showed a very pronounced dependence of the summation
      efficiency over a contrasting area on the degree of dispersion of the area. This
      is reflected in the drastic decrease upon figure dispersion of the intensity with
      which a given brightness or colour contrast is perceived. Thus, the model gives a
      better explanation and a more efficient way to approach the great capacity of the
      visual system to disclose more compact shapes or agglomeration zones in a complex
      visual scene. This capacity is to a large extent due to the increase in the
      intensity with which a given contrast is perceived, occurring in these
      conditions. This intensity, which strongly depends on the degree of concentration
      or dispersion of the figure, becomes an important additional signal leading to
      the accentuation of the difference between compact and rarefied shapes. The model
      based on the degree of concentration determined around a centre, although useful
      for finding a centre and applicable satisfactorily to many shapes, do not cover
      well all aspects of shape dispersions. In shapes without a dominant central part
      the confrontation model-testing showed an important involvement in global
      perception of all local concentrations, not only central but also peripheral, the
      later underestimated in our model. The model can be however improved by taking
      into account also such local concentrations.

PMID- 9653811
TI  - Effects of electrolytic bilateral symmetric lesions of the arcuate nucleus on the
      phagocytic activity and on the phagocytic response in rats.
AB  - Previous researches of Cluj-Napoca laboratories of Physiology (Benetato, Baciu et
      al., 1945, 1946, 1947) demonstrated that direct electrical stimulation of the
      tubero-mammillary area in dogs increases, in the following hours, the blood
      polymorphonuclears phagocytic activity. By contrast, electrical damage of the
      same region produces a depression of the basal phagocytic activity and a blocking
      of the phagocytic response (Baciu et al., 1958, 1988). In the present research we
      assumed there is a stimulating effect of the arcuate nucleus, located in this
      area, on the phagocytic activity of blood neutrophils. We used an anodal current
      to stereotaxically induce lesion of the arcuate nucleus in six rats. A control
      group of six animals was used. Five days later, phagocytic response was induced
      with a Gram negative bacterial extract given i.v. The results demonstrated a
      decrease of the phagocytic activity from 164.31 +/- 17 bacteria engulfed by 100
      neutrophils in controls, to 138 +/- 12.8 in the lesioned group p < 0.05.
      Phagocytic response after five hours appears depressed in the lesioned group (138
      +/- 12.8 to 156.25 +/- 13.3, p < 0.05). Similar results were obtained after 24
      hours. In control animals the response is very significant after 5 and 24 hrs.,
      respectively, (p < 0.001). In conclusion, the arcuate nucleus is moderately
      involved in sustaining the basal phagocytic activity of blood neutrophils. It has
      an important role in phagocytic response.

PMID- 9653812
TI  - Immunity and stress.
AB  - The relationship between stress and immunity is not a hot topic of
      psychoneuroimmunology. The review outlines the main aspects of these
      interrelations; stress sensitive immunological markers, experimental research and
      studies on humans which underline the prevailing immunosuppressive effects of
      stress are discussed. A classification of stress-related diseases comprises
      autoimmune, acute, psychosomatic and neuroendocrine diseases. Besides the
      hypothalamopituitary-adrenocortical axis and the symparthoadrenal system, newer
      information points to the role of cytokines, opioids and other mediators in the
      complex mechanisms involved. Several data from the physiological laboratory in
      Cluj are included. The final consideration outlines some unclarified aspects and
      new research directions.

PMID- 9653813
TI  - Effects of monosodium glutamate on blood neutrophils phagocytic activity and
      phagocytic response in mice.
AB  - Previous researches of our laboratories (1945, 1946, 1947) have shown that direct
      electrical stimulation of the tubero-mammillary hypothalamic area in dogs
      enhances the blood neutrophils phagocytic activity and the phagocytosis
      exhibiting leukocytes percent. After electrolytic damage of the same area,
      phagocytic activity decreases and phagocytic response is suppressed (1985, 1988).
      In the present work, we performed in mice extensive chemical lesions of the
      arcuate nucleus, by means of the neonatal treatment with monosodium glutamate
      (MSG). The experiment was carried out on 23 new-born mice. 15 mice were injected
      with MSG (G group), the other 8, serving as control group, received isotonic
      saline solution (C group). The studied parameters were, in both groups, the
      weight evolution of the animals, the blood neutrophils and lymphocytes percentual
      variation and the neutrophils' phagocytic activity, tested in vitro, expressed
      through the number of bacteria engulfed by 100 neutrophils and through the
      phagocyting neutrophils percentage. Phagocytic activity was tested in whole
      heparinised blood, against E. coli. Phagocytic response was elicited by i.p.
      injecting 0.05 ml bacterial suspension and was tested four hours later. The
      results show that the arcuate nucleus has little influence upon maintaining basal
      phagocytic activity--that does not significantly decrease after its chemical
      damage--, but plays a decisive role in triggering the phagocytic response. The
      neonatal MSG treatment also determines a decrease of the blood lymphocytes
      percentage and induces obesity in up to 30 days old mice pups.

PMID- 9653814
TI  - Investigation of immune reactivity in alcoholism with hepatic disease of various
      degrees.
AB  - The clinical and experimental investigations of alcoholic liver disease, have
      proved that hepatocytes injury is associated with immunologic abnormalities,
      which can be one of the sources of these injuries. The acetaldehyde, the main
      ethanol metabolite modify liver cytosolic proteins and form new antigens. Thus
      acetaldehyde induces the synthesis of auto-antibodies. Some hypotheses maintain
      the autoimmune pathogenesis of these diseases. Research was carried out on some
      patient groups admitted in the alcohol addiction department of the Neurology and
      Psychiatry hospital "Professor Gh. Marinescu". We have investigated the alcohol
      depending individuals with various degrees of hepatic injuries. Four groups have
      been studied: the control group, the alcohol depending patients without liver
      disease, the patients with alcoholic hepatitis, the group with alcoholic
      cirrhosis. In order to investigate the immunologic response the research has been
      carried on, along the following lines: serum immunoglobulins level, serum C3
      level, serum protein C reactive level by using IDR, serum circulating immune
      complexes by Hakova method, auto-antibodies (antinuclear AAN, antimitochondria AM
      and antismoothmuscle ASM) by using indirect immunofluorescence, T lymphocytes by
      E rosetting and lymphocytes by direct immuno-fluorescence. Clinical and
      experimental study of the alcoholic liver has shown that destruction of
      hepatocytes is accompanied by several immunological events.

PMID- 9653815
TI  - Effect of nifedipine on electrical activity of the brain in rat.
AB  - Effect of calcium channel blocker nifedipine on the electrical activity of the
      brain in anaesthetized rats was studied. The electoencephalographic signals were
      registered on a computer as series of data and thereafter they were decomposed by
      Fourier analysis in very narrow fields of frequency. The electrical activity of
      the brain of the control rats was asymmetrical, with a more important activity in
      the left brain hemisphere, particularly between 20-30 Hz when the electrical
      activity of the brain was globally more important. The nifedipine increased the
      electrical activity of the brain between 0.5-4 Hz and 20-30 Hz in a dose
      dependent manner. The drug also increased the interhemispheric asymmetry. Some
      possible explanations of these effects are analyzed.

PMID- 9653816
TI  - Experimental research on the effect of calcium channel blockers nifedipine and
      verapamil on the anxiety in mice.
AB  - The anxiolytic effect of the calcium channel blockers nifedipine and verapamil
      was tested in mice using two test: the conditioned suppression of the motility
      test and the black and white box test. The nifedipine but not the verapamil, in
      low doses (0.1 mg/kg b.w), proved anxiolytic effect and both nifedipine and
      verapamil in high dose (1.6-2.5 mg/kg b.w) had anxiogenic properties. The
      anxiogenic effect was correlated with the capacity of the drugs to block the
      calcium channels and the anxiolytic effect of low doses of the nifedipine was
      considered to be produced by opening these structures. These data were considered
      important for a new future aboard of the treatment and pathophysiology of the
      anxiety.

PMID- 9653817
TI  - A spectrophotometric assay of folic acid concentrations in rats: correlations
      with age and organ.
AB  - Spectrophotometric assays have been used to determine FA concentration in tissue
      homogenates from various organs (liver, kidneys, brain, spleen) in white rats;
      these studies were undertaken to test the age--and organ--dependent variations of
      FA concentrations in tissue homogenates. The results showed a marked decrease of
      FA concentration in the adult group of rats when related to the young group, and
      in the aged group when compared to the adults respectively. Analysing the
      determined values of folates in tissue homogenates of various organs (in rats
      belonging to the same group of age), the highest concentration has been found in
      the liver homogenate, followed in decreasing order by kidneys and to a much
      greater distance, by the brain and spleen.

PMID- 9653818
TI  - [Gastrointestinal hemorrhage of unknown origin].
AB  - Among 174 patients admitted for acute gastrointestinal bleeding the source of
      bleeding remained undetermined in 19 (10.9%) despite standard diagnostic workup.
      We show that an unknown source of acute gastrointestinal bleeding is not a risk
      factor with regard to the in-hospital outcome: there was no difference in the
      number of in-hospital days, of PRBC transfused or of surgical interventions; none
      of these patients died. While patient characteristics regarding mean age and sex
      distribution likewise did not differ, there was a significantly higher percentage
      of patients on NSAIDs or oral anticoagulants among those whose source of bleeding
      could not be found (80 vs 42%; p = 0.002). The clinical follow-up of the patients
      with undetermined source of bleeding reveals gastrointestinal pathology in a
      considerable proportion (18%); it calls for close follow-up of these patients
      after discharge.

PMID- 9653819
TI  - [Autoimmune hepatitis in Switzerland].
AB  - The incidence and course of autoimmune hepatitis in Switzerland are unknown. In
      an attempt to obtain an overview of all patients at present under treatment in
      Switzerland for autoimmune hepatitis, we circulated a questionnaire to all Swiss
      gastroenterologists. Eighteen patients were identified and their symptoms, course
      and treatment were evaluated. The majority were females, usually without liver
      cirrhosis at the time of diagnosis. The course of the disease was largely
      favourable.

PMID- 9653820
TI  - [Hemosuccus pancreaticus: a rare cause of upper gastrointestinal hemorrhage].
AB  - We report on a patient with alcoholic chronic pancreatitis and intermittent upper
      gastrointestinal haemorrhage. Old blood was seen in the duodenum but no bleeding
      source could be identified by endoscopy. Computed tomography scanner and
      angiography disclosed an arterial pseudoaneurysm of the pancreatic tail, and left
      splenopancreatectomy was performed. In cases of upper gastrointestinal
      haemorrhage, the pancreas should be considered as a bleeding source if
      endoscopies remain negative and the patient presents with chronic pancreatitis.

PMID- 9653821
TI  - [Long-term follow-up of 9 islets of Langerhans autografts after resection of the
      pancreas].
AB  - INTRODUCTION: Preservation of physiological endocrine pancreatic function
      represents a major problem in pancreatectomised patients. In 40 to 100%,
      pancreatic resection can result in diabetes, which is often difficult to manage.
      Islet autotransplantation has been proposed to prevent this severe metabolic
      consequence. PATIENTS AND METHODS: Between March 1992 and January 1997 we
      performed 9 human islet autotransplantations in Geneva. The patients comprised 6
      males and 3 females aged 40 to 81 years (median: 51 years). The pancreatectomy
      was total in 3 cases, subtotal (95%) in 2 cases and partial (40-80%) in the
      others. Indications for resection were alcohol-induced chronic pancreatitis (6
      cases) and focal benign pancreatic pathologies (3 cases). After collagenase
      digestion, unpurified islets were injected intraportally and embolised into the
      liver. Patient metabolic status was regularly tested by 24-hour serum glucose
      profile, measurement of glycosylated haemoglobin, oral and intravenous glucose
      tolerance tests and glucagon stimulation test. RESULTS: Immediately after
      autotransplantation, one patient had persistent insulin-dependent diabetes. Among
      the 8 patients who were insulin-independent soon after the graft, 4 presented a
      progressive deterioration of endocrine pancreatic function and required insulin
      therapy 5, 8, 24 and 36 months after the graft. Currently, 4 patients are insulin
      independent: three of them have normal glucose tolerance tests (24, and 48 months
      after the graft) and the last presented with glucose intolerance 22 months after
      the graft but still does not require exogenous insulin. CONCLUSION: Islet
      autotransplantation can be considered a useful therapeutic option serving to
      prevent or delay the occurrence of surgically-induced diabetes. In our opinion,
      islet autotransplantation should be offered to any non diabetic patient needing
      to undergo major pancreatic resection.

PMID- 9653822
TI  - [Isolation of the pig islets of Langerhans: evaluation of in vitro and in vivo
      function].
AB  - Pig islets are considered the best alternative to human islets in the treatment
      of insulin-dependent diabetes. Pigs could represent a potential islet donor for
      xenotransplantation in humans because of the close similarity between human and
      porcine insulin and the theoretically unlimited availability of porcine pancreas.
      From November 1991 to January 1997 we performed 221 pig islet isolations from 3
      pig sources: group 1: minipigs (age 9-18 months) and white pigs (3-8 months),
      group 2: large white pigs (5-8 months), group 3: large white pigs (12-24 months).
      Islets were isolated according to a semi-automated method using enzymatic
      digestion and purification through discontinuous Euro-Ficoll gradients. The
      pancreases were surgically removed in our laboratory for group 1, while
      pancreases from groups 2 and 3 were removed at the slaughterhouse with an average
      warm ischemia time of 15 minutes. In vitro islet function was assessed by static
      incubations and perifusions, and in vivo islet function by transplantation under
      the kidney capsule of nude diabetic mice. The results were as follows: [table:
      see text] Insulin secretion increased twofold after in vitro glucose stimulation.
      We obtained restoration of euglycemia in diabetic mice which survived > 3 months
      after the graft and returned to diabetes after nephrectomy. This study shows that
      our isolated pig islets are viable and functional in vitro and in vivo after
      transplantation.

PMID- 9653823
TI  - [Splenic vein thrombosis and chronic pancreatitis: therapeutic approach].
AB  - 10% of chronic pancreatitis (CP) cases are complicated by splenic vein thrombosis
      (SVT) which is responsible for upper digestive haemorrhages. To improve our
      approach to treatment we reviewed 30 cases of SVT associated with CP treated in
      our centre from 1985 to 1995. 14 patients were treated conservatively. Six of
      them were refused for surgery due to extension of splenic vein thrombosis into
      the portal vein. Two patients without extrinsic compression of the vein were
      treated with anticoagulants. 16 patients were treated by surgery with low
      morbidity and without mortality. The standard treatment in fourteen cases was
      splenopancreatectomy. The average follow-up of seven years shows that these
      patients have preserved their body mass index (BMI). The results suggest that
      early surgical intervention is beneficial in preventing progression of SVT to the
      portomesenteric vein.

PMID- 9653824
TI  - [Pancreatic pseudocysts: choice of treatment?].
AB  - Pseudocysts of the pancreas may require drainage or resection during their
      evolution. External drainage can be considered as a treatment of first resort
      with low related morbidity. It also offers a means of treating patients with
      major contraindications for surgery. In our experience, however, only 55% of
      external drainages prove successful. Therefore, surgical treatment, even at the
      cost of low-rate morbidity, remains the only final treatment for complications
      linked to pseudocysts of the pancreas. In the long term, however, these results
      depend on the etiology of the pseudocysts.

PMID- 9653825
TI  - [Prevalence of upper abdominal complaints and their effect on the quality of life
      and utilization of medical resources. Swiss Primary Care Group].
AB  - The authors present the results obtained in Switzerland, as part of an
      international survey (DIGEST), on 3 months' prevalence of upper digestive
      symptoms (UDS) and their influence on quality of life and consumption of medical
      services. 514 randomized adults from the general population in 8 different cities
      were interviewed. In these interviews data were recorded concerning demographic
      and socio economic aspects, quality of life, severity and frequency of UDS,
      consultations and medication. The sub-population with relevant UDS (i.e. UDS at
      least once a week and/or of moderate to severe degree) was compared with the rest
      of the population interviewed. 19% of the interviewees reported relevant UDS; of
      these, two thirds were women. No differences were found between people with and
      without UDS as far as education, professional activities, consumption of alcohol
      or smoking are concerned. The most frequent symptoms reported were fullness,
      bloating and nausea. However, daily activities were most impaired by nausea,
      epigastric pain and heartburn. Interviewees with UDS more frequently reported
      "life events" in the preceding year (48% vs 33%). Interviewees with UDS also more
      frequently reported back pain (7% vs 2%) and migraine (10% vs 6%). Furthermore,
      more interviewees with UDS reported sick leave (11% vs 3%); they also had a
      poorer life quality score (74 vs 89, PGWBI), reported more medical visits (50% vs
      19%) and consumed more medication, both prescribed (65% vs 25%) and non
      prescribed (OTC: 70% vs 31%).

PMID- 9653826
TI  - [Validation of the "Digest Questionnaire" for consistency and reproducibility
      with reference to upper abdominal symptoms].
AB  - "Digest" is a international effort to record the prevalence of digestive symptoms
      in the general population. The international questionnaire was tested in German
      translation for reliability and reproducibility. The questionnaire consists of 14
      symptoms, which were investigated by standardized questions. Each symptom was
      described in 3 dimensions: frequency, severity and impact on daily activities.
      127 successive patients referred for upper gastrointestinal endoscopy were
      interviewed twice by a young assistant and by an experienced gastroenterologist
      before the diagnostic work-up. A further 72 volunteers served as a control group.
      In these volunteers no upper gastrointestinal endoscopy was performed.
      Reliability and reproducibility were calculated by the Spearman rank test. The
      most frequent diagnoses were: organic diseases (oesophagitis [28], gastric
      ulcer/erosive gastritis [32] and duodenal ulcer [18]); functional diseases
      (dyspepsia [32] and irritable bowel syndrome [14]). Reproducibility was
      satisfactory by accepted standards (p > 0.7). Reliability was very good, with r
      values for each symptom between p 0.96-0.99. The impact on daily activities was
      highest in the case of heart-burn or localized upper gastrointestinal pain, and
      lowest in the case of belching and fullness. The questionnaire can be easily
      administered by the non-specialist and the results discriminate well between
      functional/organic diseases and healthy people, thanks to excellent
      reproducibility and reliability.

PMID- 9653827
TI  - [Intracardiac "umbrella" with anemia].

PMID- 9653828
TI  - Effects of Epoetin alfa on hemostasis in chronic renal failure.
AB  - Epoetin alfa is the cornerstone of anemia therapy in patients with end-stage
      renal disease. In addition to stimulating erythropoiesis, Epoetin alfa has been
      demonstrated to affect hemostasis. Such effects may be important because patients
      with chronic renal failure have a bleeding diathesis that is multifactorial in
      origin. Therefore, a computer literature search on the relationship between
      Epoetin alfa therapy for anemia in patients with end-stage renal disease and
      platelets, coagulation, coagulation inhibitors, and fibrinolysis was performed.
      All articles and abstracts reporting original data in the English language on
      Epoetin alfa and its effect on hemostasis were reviewed. The literature suggests
      that the effects of Epoetin alfa on the coagulation cascade are of minimal
      clinical importance. However, Epoetin alfa transiently increases the number of
      circulating platelets and improves platelet function, and these effects are
      associated with a return of the bleeding time towards normal.

PMID- 9653829
TI  - Persistent high prevalence of thyroid antibodies after immunosuppressive therapy
      in subjects with glomerulonephritis. A prospective three-year follow-up study.
AB  - The prevalence of thyroid antibodies, indicating an autoimmune thyroiditis, has
      been shown to be significantly increased in patients with autoimmune diseases. A
      3-year prospective follow-up study of 42 patients with biopsy-confirmed
      glomerulonephritis is presented. Although the majority of patients had been
      treated with immunosuppressants, the prevalence of thyroid peroxidase antibodies
      was unchanged in both females and males, 47 and 15% respectively, at follow-up.
      Likewise, the prevalence of thyroglobulin antibodies was unaffected as was that
      of antinuclear antibodies (ANA) when analysing males and females together.
      However, for males there was a trend to higher prevalence for ANA at follow-up.
      On the other hand, the prevalence of antineutrophil cytoplasmic antibodies
      declined. Furthermore, thyroid antibodies were not restricted to membranous
      nephropathy, and notably found in 4 out of the 8 patients with vasculitis.

PMID- 9653830
TI  - Determinants of ventricular arrhythmias in hemodialysis patients. Evaluation of
      the effect of arrhythmogenic substrate and autonomic imbalance.
AB  - BACKGROUND/AIMS: In chronic hemodialysis patients, we evaluated determinants of
      repetitive ventricular tachyarrhythmias which included late potentials and heart
      rate variability. METHODS: We compared the presence of late potentials and heart
      rate variability obtained by ambulatory electrocardiogram (ECG), findings of
      echocardiography, and laboratory data between patients with and those without
      ventricular arrhythmias of Lown class 4A or 4B. Ambulatory ECG was recorded for
      24 h from the beginning of hemodialysis. Heart rate variability was evaluated by
      the standard deviation of the normal RR interval (SDNN). RESULTS: Thirty patients
      (17%) had ventricular arrhythmias of Lown class 4A or 4B. They were older than
      patients without such arrhythmias (p=0.0021). Left-ventricular wall motion score
      (2.0+/-3.9 and 0.3+/-1.2, respectively, p < 0.0001) and left-ventricular mass
      index (167 +/-59 and 140+/-44 g/m2, respectively, p=0.0053) were larger in
      patients with ventricular arrhythmias of Lown class 4A or 4B than in those
      without. Stepwise logistic regression analysis was performed to select variables
      related to ventricular arrhythmias of Lown class 4A or 4B from the following 8
      candidate variables; age, sex, presence of ischemic heart disease, diabetic
      nephropathy as the primary renal disease, presence of late potentials, SDNN, left
      ventricular wall motion score and left-ventricular mass index. Higher left
      ventricular wall motion score (p < 0.0001), older age (p=0.0022) and male sex
      (p=0.0235) were the variables associated with ventricular arrhythmias of Lown
      class 4A or 4B. CONCLUSION: In patients receiving hemodialysis, predominantly
      with chronic glomerulonephritis, ventricular arrhythmias of Lown class 4A or 4B
      were not associated with arrhythmogenic substrate revealed by late potentials or
      autonomic dysfunction assessed by heart rate variability. Left-ventricular wall
      motion abnormalities, age and sex were significant factors.

PMID- 9653831
TI  - Can total urinary protein measurements predict microalbuminuria?
AB  - We re-addressed the question of whether routine total urinary protein
      determinations can be used to predict the presence of microalbuminuria by
      studying 61 patients who attended a diabetic clinic and tested negative or had
      one positive protein by dipstick. Total urinary protein was measured by the
      Biorad dye-binding method in undialyzed urine (UND), in dialyzed urine (DIAL),
      and in dialyzed urine in which albumin and globulins were separated, measured
      separately with albumin and globulin standards and the results added together to
      obtain total urinary protein (A + G). The results were compared with albumin
      measurements obtained by radioimmunoassay (RIA). Compared to DIAL, urinary
      protein measurements were 43% higher with A + G and 22% higher with UND.
      Microalbuminuria correlated moderately with UND (r =0.81) and better with the
      other methods (r=0.87 for DIAL, r=0.91 for A + G). None of the methods predicted
      microalbuminuria reliably. Taking a protein-to-creatinine ratio of 0.15 and an
      albumin-to-creatinine ratio of 0.03 as upper limits of normal, we found that UND
      had a 72% positive predictive value (28% false positives) and 85 % negative
      predictive value (15% false negatives). DIAL had 90% positive predictive value
      (10% false positives) and 78% negative predictive value (22% false negatives). A
      + G had 65% positive predictive value (35% false positives) but 91% negative
      predictive value (9% false negatives). A + G, which uses the correct standards,
      would be the most suitable method for screening, having the least number of false
      negatives, but has more false positives because it is more sensitive. In
      practice, most routine chemical laboratories find it expedient to use only UND,
      but physicians interpreting the results of this method should be aware of its
      limitations.

PMID- 9653832
TI  - Mesangial proliferative nephritis in man is associated with increased expression
      of the cell survival factor, Bcl-2.
AB  - Although most studies suggest that the hypercellularity in mesangial
      proliferative nephritis is due to increased cell proliferation, we hypothesized
      that it may also be due to increased expression of survival factors that may
      block their removal (apoptosis). We therefore studied the expression of apoptosis
      preventing/delaying the bcl-2 gene product in the glomerulus with various human
      glomerulonephritides. Immunohistochemistry for Bcl-2, proliferating cell
      associated protein (Ki-67) and alpha-smooth muscle actin (alpha-SMA) was
      performed on 55 biopsied kidney tissues: 6 cases of orthostatic proteinuria as a
      control (OP); 6 cases of diffuse proliferative lupus nephritis (WHO type IV, LN
      MPGN); 24 cases of IgA nephropathy (IgA); 9 cases of minimal change nephrosis and
      10 cases of idiopathic membranous nephropathy. The number of Ki-67-positive cells
      and the expression of alpha-SMA in the glomerulus were significantly higher in LN
      MPGN and IgA. There was a significant positive correlation between glomerular Bcl
      2 expression and glomerular cell proliferation evaluated by the number of Ki-67
      positive cells (r=0.605, p < 0.01) or glomerular alpha-SMA expression (r=0.674, p
      < 0.01). Glomerular expression of Bcl-2 in IgA or LN-MPGN was significantly
      higher than that in OP (p < 0.01 and p < 0.05 vs. OP, respectively). The Bcl-2
      positive cells were present in mesangial locations and demonstrated a perinuclear
      pattern. These results suggest that maintenance of glomerular hypercellularity in
      human glomerular diseases is partly due to the prevention of mesangial cell death
      via Bcl-2 expression.

PMID- 9653833
TI  - Predicting hemodialysis access failure with color flow Doppler ultrasound.
AB  - Color flow doppler ultrasound examination of the hemodialysis access was
      conducted in 2,792 hemodialysis patients to evaluate its value in predicting
      hemodialysis access failure. After baseline assessment of vascular access
      function with clinical and laboratory tests including color flow doppler
      evaluation these patients were followed for a minimal of 6 months or until graft
      failure occurred (defined as surgery or angioplasty intervention, or graft loss).
      The patient demographics and vascular accesses were typical of a standard
      hemodialysis patient population. On the day of the color flow doppler examination
      systolic and diastolic blood pressure, hematocrit, urea reduction ratio, dialysis
      blood flow, venous line pressure at a dialysis blood flow of 250 ml/min, and
      access recirculation rate were measured. At the conclusion of the study 23.5% of
      the patients had access failure. Case mix predictors for access failure were
      determined using the Cox Model. Case mix predictors of access failure were race,
      non-white was higher than white (p < 0.005), younger accesses had a higher risk
      than older accesses (p < 0.025), accesses with prior thrombosis had a higher risk
      of failure (p=0.042), polytetrafluoroethylene (PTFE) grafts had a higher risk
      than native vein fistulae (p < 0.05), loop PTFE grafts had a higher risk than
      straight PTFE grafts (p < 0.025), and upper arm accesses had a higher risk than
      forearm accesses (p=0.033). Most significant, however, was decreased access blood
      flow as measured by color flow doppler (p < 0.0001). The relative risk of graft
      failure increased 40% when the blood flow in the graft decreased to less than 500
      ml/min and the relative risk doubled when the blood flow was less than 300
      ml/min. This study has shown that color flow doppler evaluation, quantifying
      blood flow in a prosthetic graft, can identify those grafts at risk for failure.
      In contrast, color doppler volume flow in native AV fistulae could not predict
      fistula survival. This technique is noninvasive, painless, portable, and
      reproducible. We believe that preemptory repair of an anatomical abnormality in
      vascular access grafts with decreased blood flow may decrease patient
      inconvenience, associated morbidity, and associated costs.

PMID- 9653834
TI  - Metalloproteinase-9 mRNA expression in monocytes from patients with chronic renal
      failure.
AB  - Long-term dialysis patients suffer from various complications including
      atherosclerosis. It has been suggested that metalloproteinases (MMPs) contribute
      to vascular remodeling during the development and progression of human
      atherosclerosis. Activated human monocytes have been demonstrated to secrete
      MMPs. In the present study, we measured levels of MMP mRNA in peripheral blood
      monocytes obtained from patients on continuous ambulatory peritoneal dialysis
      (CAPD) or hemodialysis (HD) and chronic-renal-failure patients not undergoing
      dialysis. Twenty patients with chronic renal failure were not undergoing
      dialysis, 20 patients were on CAPD, 40 patients were on chronic HD and 20 healthy
      volunteers served as controls. We used cDNA probes encoding for MMP-1, MMP-2, MMP
      3 and MMP-9 and glyceraldehyde phosphate dehydrogenase. Higher levels of MMP-9
      mRNA in the peripheral blood monocytes were observed in HD patients than in CAPD
      patients, undialyzed chronic renal failure patients or healthy controls. MMP-9
      mRNA levels at the end of HD were not significantly higher than those at the
      start of HD. MMP-9 mRNA levels from HD patients did not differ among the types of
      membranes. We could detect minimal MMP-1, MMP-2 and MMP-3 mRNA expression in
      monocytes from all groups. Serum gelatinase activity was detectable in all
      samples; however, no significant differences existed among the groups. In
      summary, MMP-9 mRNA expression is enhanced in monocytes from HD and CAPD
      patients, and the enhancement may be, in part, associated with cardiovascular
      complications, including atherosclerosis, in dialysis patients. This increase in
      monocyte MMP-9 mRNA levels is lower in CAPD patients that it is in HD patients.

PMID- 9653835
TI  - A simple assessment of peritoneal transport in stable continuous ambulatory
      peritoneal dialysis patients.
AB  - We studied the peritoneal transport properties in 175 stable continuous
      ambulatory peritoneal dialysis (CAPD) patients seeking a simple and handy
      assessment of peritoneal permeability to small solutes. Measurement of creatinine
      in biological fluid was known to suffer from interference by high glucose
      concentration in the sample. Furthermore, the interference is also affected by
      the creatinine concentration of the specimen. Peritoneal transport properties
      were studied by determining the dialysate to plasma ratio of creatinine
      concentration (D/P) at the fourth hour of the peritoneal equilibration test, and
      the mass transfer area coefficient of creatinine (MTACCr) or glucose (MTACGlu).
      The ratio of glucose concentration in peritoneal dialysate effluent (PDE) at 4
      and 0 h (G4/G0) was examined and compared with various peritoneal parameters.
      There were significant logarithmic correlations between D/P or G4/G0 with MTACCr
      (r=0.96 and 0.79, respectively, p < 0.0001). The correlation between G4/G0 and
      D/P was linear (r=-0.82, p < 0.0001). A fairly good agreement was present between
      G4/G0 and D/P by Bland and Altman's method. The bias was -0.93% with 95%
      confidence interval -23.29% to 21.43% of the measured value. Systematic error was
      found when D/P or G4/G0 were compared with MTACCr. D/P under estimated MTACCr in
      the high range. The reverse happened for G4/G0. Net ultrafiltration (NUF) also
      correlated with MTACCr, D/P and G4/G0 (r=-0.32, p < 0.001; -0.26, p < 0.01; and
      0.16, p < 0.05, respectively. In conclusion, the use of G4/G0 as a measure of
      peritoneal transport in CAPD is an acceptable alternative to D/P. It is highly
      reproducible and avoids correction of interference when creatinine transport
      parameters are measured. Because of the logarithmic relations of G4/G0 (or D/P)
      with MTACCr, the former should not be directly converted to MTACCr. Such a simple
      measure of peritoneal permeability is, however, most convenient for serial
      monitoring and can be useful to detect early loss of ultrafiltration or solute
      clearance.

PMID- 9653836
TI  - Duodenal obstruction in polycystic kidney disease. Case report and review of the
      literature.
AB  - Polycystic kidney disease in a common inherited disorder accounting for 8-10% of
      cases of end-stage renal disease. The enlarged kidneys often produce pain and
      hematuria but rarely obstruction of surrounding organs. We report a case of
      autosomal dominant polycystic kidney disease producing symptomatic duodenal
      obstruction and malnutrition. Duodenal obstruction should be considered in the
      differential diagnosis of a patient with polycystic kidney disease and
      intermittent or persistent nausea and vomiting.

PMID- 9653837
TI  - End-stage renal failure due to crescentic glomerulonephritis in a patient with
      Behcet's syndrome. Review of the literature.
AB  - We report a rare case of a patient with Behcet's syndrome who developed end-stage
      renal failure due to crescentic glomerulonephritis (GN). A 20-year-old male
      patient had suffered from uveitis, aphthous mouth ulcers and genital ulceration
      for the past 7 years. His renal function rapidly deteriorated and renal biopsy
      specimens obtained when his serum creatinine level was 3 mg/dl showed diffuse
      proliferative GN with fibrous crescent formation in 75% of glomeruli excluding
      totally sclerotic glomeruli. Immune complexes were identified by demonstration of
      complement and immunoglobulins in the glomeruli. He developed end-stage renal
      failure during a 1-year course and received maintenance hemodialysis. We reviewed
      the literature on severe forms of GN in patients with Behcet's syndrome.

PMID- 9653838
TI  - Treatment of pulmonary embolism by subcutaneous low-molecular-weight heparin in a
      hemodialysis patient.
AB  - Low-molecular-weight heparin (LMWH) has been used in the prophylaxis and
      treatment of deep vein thrombosis. Data regarding the efficacy of this drug
      without subsequent use of oral anticoagulant in the treatment of pulmonary
      embolism is limited. Pulmonary embolism may complicate the use of central venous
      catheter in hemodialysis. We report a case of acute submassive pulmonary embolism
      complicating a central venous hemodialysis catheter in a dialysis patient. After
      the catheter was removed, the patient was treated successfully with subcutaneous
      injection of LMWH for three months. We conclude that LMWH is safe and effective
      for treatment of pulmonary embolism in patient on hemodialysis.

PMID- 9653839
TI  - Acute anuric renal failure in nonfulminant hepatitis A infection.
AB  - Acute renal failure has recently been recognized as a rare complication of
      nonfulminant hepatitis A infection. The availability of a specific test for IgM
      antibody to hepatitis A should permit prompt diagnosis of the disease and a
      better evaluation of its association with acute renal failure. The exact
      mechanism for acute renal failure in hepatitis A is uncertain but
      glomerulonephritis, acute tubular necrosis and hepatorenal syndrome have been
      postulated. We report a patient with hepatitis A infection and acute renal
      failure most likely due to acute tubular necrosis.

PMID- 9653840
TI  - Systemic involvement and uremia in a patient with tuberous sclerosis.

PMID- 9653841
TI  - Immunotactoid glomerulopathy associated with idiopathic hypereosinophilic
      syndrome.
AB  - A case of immunotactoid glomerulopathy in an 18-year-old man with an idiopathic
      hypereosinophilic syndrome is presented. The patient showed cervical
      lymphadenopathy, asymptomatic proteinuria of nephrotic range, and hematuria
      without any defined immunologic disease. Marked and prolonged hypereosinophilia
      was found in peripheral blood (eosinophil count; 6,248/mm3) and bone marrow
      (eosinophil series; 32%). Diffuse and/or nodular eosinophilic infiltration was
      identified in multiple organs such as kidney, stomach, liver, lymph node, and
      skin. Renal biopsy revealed endocapillary proliferative features of typical
      immunotactoid glomerulopathy with IgG and C3 deposition and microtubular
      structures of variable size, 20-80 nm in diameter, mainly in the subendothelium.
      This study suggests that immunotactoid glomerulopathy may be a secondary
      immunologic manifestation of the tissue damage by eosinophils in the idiopathic
      hypereosinophilic syndrome.

PMID- 9653842
TI  - Oxidative modification of low-density lipoprotein enhances mesangial cell protein
      synthesis and gene expression of extracellular matrix proteins.
AB  - The proliferation of intrinsic glomerular cells and the accumulation of
      extracellular matrix proteins are principal histopathological features seen in
      glomerular injury. Because of the marked similarity between the cellular and
      molecular events that occur in both atherosclerosis and glomerulosclerosis and
      the commonly accepted hypothesis that lipoproteins are implicated in the
      pathogenesis of glomerulosclerosis, we examined the effect of three atherogenic
      lipoproteins, low-density lipoprotein (LDL), oxidized (ox)-LDL, and minimally
      modified (mm)-LDL on the synthesis and secretion of extracellular matrix (ECM)
      proteins by mesangial cells. The incubation of SV-40 transformed murine mesangial
      cells with LDL (25-100 microg/ml) increased the synthesis and secretion of both
      fibronectin and laminin in a dose-dependent manner. Similarly, oxidized forms of
      LDL (25-100 micro/ml) increased fibronectin and laminin synthesis and secretion
      dose dependently. However, both oxidatively modified forms of LDL had a greater
      effect on increasing ECM protein synthesis than their native counterpart.
      Northern blot analysis showed a dose-dependent increase in mRNA transcripts for
      fibronectin and laminin in response to the incubation of mesangial cells with
      LDL, ox-LDL, and mm-LDL. Similar to the ECM protein expression data, the
      oxidatively modified forms of LDL had more pronounced effects on the gene
      expression of both fibronectin and laminin. These data show that both LDL and,
      perhaps more importantly, its oxidatively modified forms stimulate mesangial
      cells to upregulate both the gene expression and synthesis and secretion of ECM
      proteins, supporting a role for atherogenic lipoproteins in the pathobiology of
      glomerular injury.

PMID- 9653843
TI  - Arterial CO2 tension in metabolic acidosis.

PMID- 9653845
TI  - Incidence of preterm delivery in Hong Kong Chinese.
AB  - A retrospective analysis of the obstetric database between January, 1995 and
      December, 1996 was conducted to establish the rate of preterm birth and the
      incidence of babies with low birth-weight amongst Hong Kong Chinese in an
      obstetric teaching unit in Hong Kong, and to investigate possible risk factors
      for spontaneous preterm deliveries. In the series of 13,641 Chinese women who
      delivered during the study period, the incidence of preterm births before 37
      weeks' gestation was 7.4% while the incidence of low birth-weight infants
      (<2,500g) was 6.4%. When only singleton pregnancies were included, the incidences
      of preterm births and low birth-weight were 6.5% and 5.1% respectively. This
      study has demonstrated results contrary to the belief that premature delivery is
      uncommon in a Chinese population. In addition, we have found that, similar to
      Caucasian populations, hypertensive disorders of pregnancy, gestational diabetes,
      antepartum haemorrhage and congenital malformation are significant risk factors
      for spontaneous preterm labour in singleton pregnancy in our Chinese population.

PMID- 9653844
TI  - Differences in obstetrical and gynaecological diseases in different populations:
      prevalences of prematurity, congenital malformations, prolapse, genital tract
      carcinomas and infections.

PMID- 9653846
TI  - Hormone replacement therapy in the developing countries.
AB  - The sales data of oestrogen replacement products for 8 developing countries from
      1993 to 1995 were analyzed. The data from Malaysia, Pakistan, Taiwan, Thailand,
      Indonesia, Philippines and South Korea showed the increasing use of oestrogen
      replacement products. The total usage however varied widely, from only US$11,153
      (Philippines in 1993) to as much as US$6,306,717 (Taiwan in 1995). In Singapore,
      where oestrogen replacement is an accepted and established form of therapy for
      the postmenopausal woman, there has been an increase in the usage of the
      nonoestrogen replacement products. There are multiple reasons for the increasing
      sales of hormone replacement products in the developing countries and these are
      explored in this article. In some of the developing countries, for example China
      and India, hormone replacement therapy has just been introduced. However, in
      those developing countries in which hormone replacement therapy is already
      available, sales figures show increasing usage. The future augurs well for
      hormone replacement therapy.

PMID- 9653847
TI  - A systematic review of single-dose intramuscular methotrexate for the treatment
      of ectopic pregnancy.
AB  - The use of single-dose intramuscular methotrexate for the primary treatment of
      ectopic pregnancy is increasing in frequency in many countries. We performed a
      systematic review of all available studies and case reports of intramuscular
      methotrexate to examine the therapeutic efficacy, side-effects and complication
      rates of this new treatment approach. The pooled data show a successful
      resolution rate of 71% (95% confidence interval 58% to 81%) after a single dose
      of intramuscular methotrexate and 84% (95% confidence interval 77% to 90%) after
      1 or 2 doses. Side-effects were experienced by 24% (95% confidence interval 9% to
      47%) of patients and 10% (95% confidence interval 7% to 14%) had a ruptured
      ectopic pregnancy. The pooled data show that single-dose intramuscular
      methotrexate is associated with a high failure rate. Follow-up is prolonged and
      there is a significant incidence of minor side-effects. Serious complications and
      side-effects have occurred. The use of intramuscular methotrexate should be
      confined to clinical trials until more evidence is obtained to support its more
      widespread use.

PMID- 9653848
TI  - Heterotopic pregnancy complicating in vitro fertilization.
AB  - A review was undertaken of the cases of heterotopic pregnancy resulting from in
      vitro fertilization/embryo transfer (IVF/ET) and frozen embryo replacement (FER)
      in a 6-year cohort of women at National Women's Hospital in Auckland. The
      incidence of heterotopic pregnancy was 2.9% (5 cases) in 173 clinical pregnancies
      resulting from 901 embryo replacements. Of the 5 women with heterotopic
      pregnancy, 1 had unilateral tubal patency and 4 had bilateral tubal blockage; 3
      had 'high responder' peak serum oestradiol levels (greater than 9,000 pmol/L)
      prior to oocyte pick-up (OPU); 3 had a serum human chorionic gonadotrophin beta
      subunit (beta-HCG) level greater than 600 IU/L on Day 14 following embryo
      transfer (ET) in the absence of a multiple intrauterine gestation on subsequent
      ultrasound scan. In the 4 women in whom unequivocal diagnosis of heterotopic
      pregnancy was not made on the initial ultrasound scan, there was delay in
      appropriate management, in 1 for more than 5 months. In conclusion, early IVF
      pregnancies require a transvaginal ultrasound scan performed by a sonographer
      experienced in the diagnosis of ectopic pregnancy and management of early
      pregnancy complications by clinicians in close consultation with the IVF centre
      itself. No single risk factor, laboratory test or combination of these is
      sensitive or specific enough to predict the occurrence of heterotopic pregnancy.
      The first-line surgical treatment of heterotopic pregnancy should be laparoscopic
      salpingectomy with excision of all except the intramural portion of the affected
      Fallopian tube.

PMID- 9653849
TI  - Haemoperitoneum due to cornual endometriosis during pregnancy resulting in
      intrauterine death.

PMID- 9653850
TI  - Genital tract fistula repair on 116 women.
AB  - A personal series of 130 genital tract fistula repairs in 116 women is presented.
      All fistulas were repaired vaginally. The majority of the fistulas were due to
      obstetric injuries, especially prolonged obstructed labour. Obstetric fistula
      continue to be a cause of personal and social morbidity to sufferers.

PMID- 9653851
TI  - Abnormal cervical cytology in pregnancy: experience of 811 cases.
AB  - This paper reviews our hospital's experience spanning 15 years and involving 811
      women referred with abnormal cervical cytology in pregnancy. It supports the
      safety and accuracy of managing dysplasia in pregnancy with colposcopy, directed
      punch biopsy and deferral of treatment until the postpartum period. The
      histologically-proven progression in pregnancy to a higher grade of dysplasia
      postpartum was 7%. None of the women are known to have developed microinvasive or
      invasive cancer between antenatal assessment and postpartum review. Of these 811
      women, 16% were lost to follow-up, 1 of whom subsequently represented 4 years
      later with invasive cervical cancer.

PMID- 9653852
TI  - Perioperative documentation: are we doing enough?
AB  - We performed a retrospective analysis to assess the content and accuracy of
      operative and anaesthetic records for Caesarean section in a large unit. The
      obstetric record was considered adequate if it included patient identification,
      participating doctors, operative date, title, details and findings and a
      signature. The anaesthetic record was evaluated by The Australian and New Zealand
      College of Anaesthetists guidelines. We analysed 104 operative and 101
      anaesthetic records. There was inadequate identification in 17 (16.3%) of the
      operative records. Documentation of a previous scar or the presence or absence of
      intraabdominal adhesions was incomplete in 22 of the 35 patients (63%) with a
      previous laparotomy. Sixty per cent of records had incomplete skin closure
      information. Common anaesthetic record deficiencies were patient position,
      patient airway, investigation results and postoperative plan. Our findings
      identified deficiencies that could lead to inadequate medical care and indicate
      the need for improved standards of perioperative records.

PMID- 9653853
TI  - Oral medication for post-Caesarean analgesia.
AB  - A regimen of morphine, paracetamol and aspirin administered orally was evaluated
      in 20 patients following Caesarean section; 18 of 20 reported no or mild
      impairment in their ability to care for their babies. There was a high level of
      satisfaction with 18 of 20 being very satisfied with their postoperative
      analgesia. There was a low incidence of side-effects with this regimen. It was
      acceptable to both patients and staff.

PMID- 9653854
TI  - Do multiple measurements employing different ultrasonic techniques improve the
      accuracy of amniotic fluid volume assessment?
AB  - This investigation was undertaken to determine if the accuracy of the ultrasound
      assessment of abnormal amniotic fluid volume (oligohydramnios or polyhydramnios)
      is improved by employing multiple sonographic amniotic fluid measurements. Four
      ultrasound techniques consisting of the subjective assessment (ultrasonic
      visualization without measurement), largest vertical pocket, amniotic fluid index
      and 2-diameter pocket technique were performed followed by amniocentesis and dye
      dilution confirmation of amniotic fluid volume in 66 singleton pregnancies. The
      ultrasound accuracy to detect abnormal amniotic fluid volume ranged from 61% with
      the largest vertical pocket to 70% with the 2-diameter pocket procedure used
      separately. Receiver operator characteristic curves demonstrated that combining
      the 4 ultrasonic measurements did not improve the accuracy of identifying
      amniotic fluid volumes.

PMID- 9653855
TI  - The relationship between weight gain in pregnancy, birth-weight and postpartum
      weight retention.
AB  - A total of 292 middle class, nonsmoking Chinese patients with known prepregnant
      weight who subsequently had uncomplicated singleton pregnancies delivering after
      36 weeks' gestation were recruited to assess their serial antenatal weight gain,
      weight at 6 weeks and 3 months postpartum. The average prepregnant body mass
      index in the whole group was 20.4 kg/m2 (SD 2.19), and the total pregnancy weight
      gain was 14 kg (SD 3.75). Those with weight gain over 17.83 kg (one SD above the
      mean) (n=58) had higher weight gain in all 3 trimesters taken separately, as well
      as higher weight retention at 6 weeks and 3 months postpartum (p <0.001). Similar
      differences were noted for those with total weight gain over 2 standard
      deviations above the mean. The average weight retained at 3 months postpartum was
      3.64 kg (SD 2.75). Those with weight retention over 9.14 kg (2 SD above the mean)
      (n=8) had a significantly higher second and third trimester weight gain (p <0.01)
      compared to the rest. These data suggest that excessive weight gain during
      pregnancy for women with prepregnant BMI in the normal range occurred most
      significantly after the mid-trimester, and was associated with higher postpartum
      weight retention without significant increase in birth-weight.

PMID- 9653856
TI  - Cystic fibrosis and pregnancy.
AB  - The case records of 11 patients with cystic fibrosis (CF) who had 13 completed
      pregnancies between 1975 and 1995 were retrospectively reviewed to assess: (1)
      the changes in spirometry and body mass index (BMI) during pregnancy; and (2)
      maternal and neonatal complications and outcomes. Prepregnancy the mean age of
      the group was 24 (range 17-27) years. Two patients were exsmokers, 7 had
      pancreatic insufficiency and 7 had chest X-ray evidence of bronchiectasis. None
      of the patients had diabetes mellitus but 3 developed gestational diabetes. The
      mean +/- SEM (% predicted) forced expiratory volume in 1 second (FEV1) and forced
      vital capacity (FVC) prepregnancy were 2.3 +/- 1.0 (83%) litres and 3.0 +/- 0.9
      (85%) litres respectively. Five patients had normal spirometry (FEV1 and FVC >80%
      predicted) prior to 6 pregnancies. The mean body mass index (kg/height(m)2) for
      the group was 20.5 +/- 2.0. There was a significant decline in spirometry during
      pregnancy (FEV1 15.5 +/- 6.6% p<0.01; FVC 14.0 +/- 8.3% p<0.5). However, FVC but
      not FEV1 recovered to prepregnancy values by 12 months postpartum. There was a
      significant increase in both weight (7.1 kg) and BMI (2.6 kg/height(m)2) at the
      time of delivery compared with prepregnancy (p=0.0004). However, postpregnancy
      both weight and BMI had returned to their prepregnancy values (p<0.2). Mothers
      with an FEV1>80% had less decline in FEV1 related to pregnancy, better outcomes,
      fewer operative and instrumental deliveries, fewer preterm infants and fewer
      neonatal complications. Suggestions for the planning and management of pregnancy
      in women with CF are discussed.

PMID- 9653857
TI  - Study of cervicovaginal fetal fibronectin status to guide treatment of threatened
      preterm labour.
AB  - A sequential controlled pilot study of 48 women (16 study, 32 controls) was
      performed to explore the place of bedside fetal fibronectin testing in the
      management of apparent preterm labour; 80% of the study group were successfully
      managed without tocolytic therapy, on the basis of fetal fibronectin test
      results, without detriment to the babies. Rapid bedside fetal fibronectin testing
      holds promise that protocols for management of women in apparent preterm labour,
      with intact membranes and without significant cervical dilatation, may be altered
      so that most of the unnecessary use of tocolytic drugs is avoided.

PMID- 9653858
TI  - Diet and nutrition: a knowledge, attitude and practice study of pregnant women in
      Karachi.

PMID- 9653859
TI  - Which Korotkoff sound should be used for the diastolic blood pressure in
      pregnancy?
AB  - There is a gathering momentum favouring the adoption of the 5th Korotkoff sound
      to identify diastolic blood pressure in pregnancy. Our objective was to measure
      interobserver reliability for indirect blood pressure measurement in pregnancy
      for systolic and diastolic measurements and to calculate the difference in
      diastolic pressure measured by the 4th and 5th Korotkoff sounds. To minimize bias
      we used trained but previously inexperienced observers with proven, normal
      auditory acuity. The observers were paired in 4 teams and performed a series of
      334 blinded, simultaneous observations of systolic and diastolic blood pressure
      measurements taken from pregnant women between 12-41 weeks' gestation.
      Reliability was measured by intraclass correlation coefficient for paired
      measures and kappa for the detection or nondetection of 4th (K4) and 5th (K5)
      Korotkoff sounds. K4 was undetected in 36% of observations and K5 was undetected
      in 2% of observations. Reliability for detection or nondetection of Korotkoff
      sounds was fair for K4 (kappa 0.36) and moderate for K5 (kappa 0.58). Reliability
      was good between observers for systolic, K4 and K5 diastolic measurements
      (intraclass correlation > or = 0.80). The mean difference between the diastolic
      pressure measured by K4 and K5 was 15 mmHg for all measurements and 8 mmHg for
      the top quartile of measurements (p <0.001). We found K5 to be more often and
      more reliably detected than K4. If units adopt K5 in preference to K4,
      consideration will need to be given to lowering treatment thresholds for women
      with borderline or mild hypertension.

PMID- 9653860
TI  - Blood pressure measurement in pregnancy--a survey of methods used in teaching
      hospitals in South Australia.
AB  - A voluntary, anonymous 10-point multiple choice questionnaire was used to assess
      variability in methods used to measure blood pressure in pregnancy in 5 South
      Australian teaching hospitals. Medical and midwifery staff working in maternity
      units attached to teaching hospitals in South Australia were asked to complete a
      survey of their current practice related to the measurement of blood pressure in
      pregnant women; 213 replies were received from 440 surveyed (48% response rate).
      There was a lack of standardization of practice for: positioning of the patient,
      use of the 4th or 5th Korotkoff sound for diastolic blood pressure, cuff
      selection, rounding of the measurement, selection of the left or right arm, and
      period of premeasurement resting. Systematic errors averaging 10-15 mmHg can be
      expected in measurement of blood pressure in pregnancy due to failure of
      standardization of method. There is a need for standardization of method which is
      not being met by present methods of staff training in teaching hospitals.

PMID- 9653862
TI  - Fetal biomodelling.
AB  - A study has been performed to determine if a stereolithographic (SL) biomodel of
      a fetal face could be created from 3 dimensional (3D) ultrasound (US). 3D
      ultrasound images were acquired by Diasonics Gateway 2D Array ultrasound systems
      (Diasonics Ultrasound, San Jose, CA, USA) using an electromagnetic localizer
      (Tomtec Free Hand Scanning Device, Tomtec Imaging Systems, Middle Cove,
      Australia). 3D volumetric reconstruction of the fetal face was performed and the
      data was prepared to guide the construction of an exact solid biomodel by
      stereolithography (SLA 250 3D Systems, Valencia, CA, USA). A faithful solid
      representation of the fetal face was produced within 12 hours of the US scan. The
      fetal biomodel seemed to improve the display of the 3D data. The user-friendly
      nature of biomodelling may have clinical utility for fetal morphological
      assessment and as an aid when counselling parents.

PMID- 9653861
TI  - Changes of resistance to activated protein C in the course of pregnancy and
      prevalence of factor V mutation.
AB  - The purpose of this study was to examine the changes in activated protein C (APC)
      anticoagulant activity during pregnancy and determine whether changes in APC
      could contribute to thrombosis in the placental bed in preeclampsia. We measured
      APC anticoagulant activity in 150 women with a normal pregnancy and 50 women with
      preeclampsia. There was a significant reduction in the mean APC sensitivity ratio
      (APC-SR) during pregnancy (p<0.001). APC resistance in preeclampsia was
      significantly higher than in normal pregnancy (p<0.01). Amongst women with APC
      resistance the presence of the factor V Leiden mutation was significantly higher
      in the preeclampsia group than in the normal pregnancy group (p<0.01). It seems
      that both factor V Leiden mutation and APC resistance may be associated with the
      development of preeclampsia. These results suggest that APC resistance may be an
      important mechanism underlying placental bed pathology in pregnancy and may be
      associated with an increased tendency to develop preeclampsia in some women.
      Assay of APC resistance and factor V Leiden mutation should be performed in women
      with preeclampsia.

PMID- 9653863
TI  - The effects of human amniotic membrane and fibrin sealant in the prevention of
      postoperative adhesion formation in the rabbit ovary model.
AB  - The study group consisted of 29 female, white New Zealand rabbits. The rabbits
      were randomized into 3 groups and a midline laparotomy was performed in order to
      make a 4-5 mm long lesion using a scalpel in both ovaries. In Group 1, both of
      the ovaries were left uncovered. In Group 2, the right ovaries were covered by
      human amniotic membrane graft. In Group 3, 0.1-0.2 mL of Tisseel solution was
      applied to the lesion in the right ovaries. No medication was applied to the left
      ovaries in any of the groups and thus this ovary acted as an individual control.
      After 2 weeks the adhesion scores were graded by relaparotomy in a blind manner.
      Fibrin sealant showed a significant reduction in postoperative adhesion formation
      compared with the amniotic membrane graft and control groups (p<0.001).
      Therefore, it can be concluded that fibrin sealant can be used as an adjuvant
      during reproductive surgery.

PMID- 9653864
TI  - The effects of danazol after endometrial resection--results of a randomized,
      placebo-controlled, double-blind study.
AB  - We report the results of a controlled, randomized, prospective, 'double blind'
      evaluation of the effect of danazol treatment in 120 patients after hysteroscopic
      endometrial resection. After endometrial resection, the women were allocated to 1
      of 3 groups: Group A- placebo; Group B - high-dose danazol (600 mg daily); Group
      C - low-dose danazol (200 mg daily) plus placebo tablets. Tablets were
      specifically manufactured for the study, were identical in appearance, and were
      supplied in individual prepackaged boxes. The duration of treatment was 3 months
      and patients' compliance was noted. Amenorrhoea, dysmenorrhoea and premenstrual
      tension symptoms were assessed for each group by 1 or 2 independent
      gynaecologists at follow-up intervals of 6 weeks, 3, 6 and 12 months. A
      statistically-significant increased rate of amenorrhoea was found in patients who
      received treatment with the higher-dose danazol (600 mg day) following
      endometrial resection. While not statistically significant, the same trend was
      noted with the low-dose danazol. This result should influence our clinical
      management of women with menorrhagia, and the long-term results on the same
      cohort of patients are awaited with interest.

PMID- 9653865
TI  - Microlaparoscopy for suspected pelvic pathology--a comparison of 2mm versus 10mm
      laparoscope.
AB  - This study presents an independently-assessed comparison of the laparoscopic view
      obtained using a 2mm versus 10mm laparoscope in women with suspected pelvic
      pathology. Fifteen female volunteers booked for laparoscopy with clinical
      evidence of pelvic abnormality according to clinical findings and/or pelvic
      ultrasound were recruited for this study. Sequential observations were carried
      out by independent observers for clinically significant differences. Although
      discrepancies were noted in 3 patients the view obtained with the 2mm
      microendoscope was considered to be comparable to that obtained with the 10mm
      telescope. The cases with discordant findings included mild or minimal
      endometriosis and distal tubal disease. The results of this study suggest that
      microendoscopy is likely to be entirely adequate for many routine laparoscopic
      procedures and sterilization.

PMID- 9653866
TI  - Fetal brain death syndrome--a case report and literature review.
AB  - This case describes a new feature of fetal brain death syndrome, abnormal
      movements mimicking fetal convulsions being subsequently found to be decerebrate
      hypertonicity in a brain-dead fetus. It also confirms the diagnostic criteria of
      fetal brain death, both clinical and ultrasonic. The development of
      polyhydramnios both prior to and after the presumed neurological event is
      suggested as an association with the diagnosis of fetal brain death. Increased
      awareness of this event and the heterogeneity of the presentation may prevent
      further unnecessary Caesarean sections, as to date only 4 of the 10 cases in the
      literature were diagnosed prenatally. Utilization of techniques such as fetal
      blood sampling should be considered to further delineate the diagnosis.

PMID- 9653867
TI  - Thyroxine abuse: an unusual case of thyrotoxicosis in pregnancy.
AB  - Eating disorders and the associated behavioural problems and drug abuse are
      uncommon in pregnancy. When they do occur they are often unrecognized because of
      denial but when significant may pose a risk to both the mother and her fetus.
      This case illustrates a number of problems that may be encountered in women with
      eating disorders in pregnancy, including prolonged and recurrent metabolic
      disturbances and diuretic abuse. In particular it illustrates the derangements of
      thyroid function seen in pregnant women with eating disorders and reminds us that
      when a cause for thyrotoxicosis remains obscure, thyroxine abuse should be
      considered and explored.

PMID- 9653868
TI  - A case report of Sheehan syndrome presenting with diabetes insipidus.
AB  - Hypopituitarism caused by necrosis of the physiologically enlarged pituitary
      gland of pregnancy following postpartum haemorrhage was first described by
      Sheehan (1). Although manifestations of the clinical syndrome are most often
      caused by deficiencies of hormones of the anterior pituitary gland, involvement
      of the posterior lobe of the pituitary gland although rare has been described
      (2,3). This is a report of a case of diabetes insipidus developing within 24
      hours postpartum in a grand multipara who had an elective lower segment Caesarean
      section for twins.

PMID- 9653869
TI  - Successful pregnancy in a patient with previous bladder exstrophy.
AB  - Bladder exstrophy is an unusual congenital anomaly. Patients becoming pregnant
      with such anomaly after surgical repair are even rarer. The present case reports
      a lower segment Caesarean section delivery of a living healthy baby in a woman
      who had been operated on for bladder exstrophy at the age of 18 years. This is
      the first case of this type seen in our institution in 35 years.

PMID- 9653870
TI  - A case of transvaginal evisceration.
AB  - We present a case of spontaneous evisceration of the small bowel through the
      vaginal vault in a 61-year-old women. The predisposing factors and management are
      discussed.

PMID- 9653871
TI  - Strangulation of the small intestine: a late complication of ventrosuspension.

PMID- 9653872
TI  - Assessment and management of female urinary incontinence--a survey of current
      practice.
AB  - A survey of conference delegates attending the Urogynaecology Day at the 1997
      Annual Scientific Meeting of the Royal Australasian College of Surgeons indicated
      that practitioners are inconsistent in their approach to the use of preoperative
      urodynamics evaluation for women with stress incontinence and disagree about the
      significance of the low pressure urethra.

PMID- 9653873
TI  - The use of gemeprost pessaries to arrest postpartum haemorrhage.

PMID- 9653874
TI  - Effects of S-8510, a novel benzodiazepine receptor partial inverse agonist, on
      basal forebrain lesioning-induced dysfunction in rats.
AB  - We investigated the effects of a novel benzodiazepine partial inverse agonist, S
      8510 (2-(3-isoxazolyl)-3,6,7,9-tetrahydroimidazo [4,5-d] pyrano [4,3-b] pyridine
      monophosphate monohydrate), on the impairment of spatial memory, decreased high
      affinity choline uptake and acetylcholine release in basal forebrain-lesioned
      rats. S-8510 (3 and 5 mg/kg, p.o. 30 min before each training session)
      significantly ameliorated the basal forebrain-lesion-induced impairment of
      spatial memory in water maze task. In vivo brain microdialysis studies showed
      that systemic administration of S-8510 at 3 and 10 mg/kg significantly increased
      the release of acetylcholine in the front-parietal cortex in basal forebrain
      lesioned rats. Further, repeated administration of S-8510 (3 and 10 mg kg(-1)
      day(-1) for 5 days) reversed the decrease in cortical high-affinity choline
      uptake induced by basal forebrain lesion. Thus, S-8510 improved the spatial
      memory impairment induced by lesion of the basal forebrain in rats. In addition,
      it increased acetylcholine release and high-affinity choline uptake from the
      cortex, a region closely associated with memory, in basal forebrain-lesioned
      rats. These results indicate that S-8510 has cognition enhancing and cholinergic
      activating effects in the basal forebrain-lesioned rats, suggesting that this
      agent may be useful for the treatment of mild to moderate senile dementia
      including Alzheimer's disease.

PMID- 9653875
TI  - Differential effects of selective adenosine A1 and A2A receptor agonists on
      dopamine receptor agonist-induced behavioural responses in rats.
AB  - The effects of the systemic (i.p.) administration of the selective adenosine A1
      receptor agonist N6-cyclopentyladenosine (CPA) and the selective adenosine A2A
      receptor agonist sodium 2-p-carboxyethyl)phenylamino-5'-N-carboxamidoadenosine
      (CGS 21680) on different dopamine receptor agonist-induced behaviours were
      studied in the male rat. CGS 21680 (1 micromol/kg), but not CPA, was found to
      counteract the stereotypies induced by the non-selective dopamine receptor
      agonist apomorphine (0.25 mg/kg s.c.). Low doses of CGS 21680 (0.1 micromol/kg)
      and high doses of CPA (3 micromol/kg) counteracted yawning induced by the
      dopamine D2 selective agonist quinpirole (0.05 mg/kg). On the other hand, low
      doses of CPA (0.3 micromol/kg) antagonized grooming induced by the selective
      dopamine D1 receptor-selective agonist SKF 38393 (10 mg/kg i.p.), while CGS 21680
      was ineffective. These results are consistent with the proposed existence of a
      selective antagonistic modulation of dopamine D1 and D2 receptors by adenosine A1
      and A2A receptors, respectively. The ability of CGS 21680 to counteract
      apomorphine-induced stereotypies is weaker compared to its previously reported
      antagonistic effect of amphetamine-induced motor activity. This supports the
      hypothesis that adenosine A2A receptor agonists may be potential antipsychotic
      drugs with a low potential for extrapyramidal side effects.

PMID- 9653876
TI  - Footshock-induced rise of rat blood histamine depends upon the activation of
      postganglionic sympathetic neurons.
AB  - We have previously shown the existence of a novel peripheral reflex inhibitorily
      modulating the vas deferens sympathetic activity. An interaction between
      noradrenergic and histamine-containing neurons is involved in this reflex. As an
      overall mechanism of sympathetic autoregulation, we found that enhanced
      sympathetic activity in the rat during the stress induced by brief inescapable
      footshocks caused a marked rise of blood histamine that was seemingly dependent
      upon sympathetic activity. This rise was prevented by either previous ganglionic
      blockade with hexamethonium or chronic guanethidine-induced sympathectomy.
      Previous adrenal demedullation did not impair this rise. Thus, it appears that
      only the sympathetic postganglionic neuron, interacting with a histamine
      containing neuron, is involved in the rise of blood histamine induced by
      footshocks.

PMID- 9653877
TI  - Inflammation alters the effects of mGlu receptor agonists on spinal nociceptive
      neurones.
AB  - Several types of metabotropic glutamate receptor are known to be located in the
      spinal cord. This study examined the effects of the metabotropic glutamate
      receptor agonists (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)
      ACPD), (S)-3,5-dihydroxyphenylglycine ((S)-3,5-DHPG) and (1S,3S)-1
      aminocyclopentane-1,3-dicarboxylic acid ((1S,3S)-ACPD) on the electrically evoked
      responses of dorsal horn neurones recorded in normal animals and in animals 3 h
      after the induction of carrageenan inflammation. The group I and II agonist
      (1S,3R)-ACPD produced facilitations of the noxious evoked neuronal responses in
      normal animals, but inhibited these responses following carrageenan inflammation.
      The group II agonist (1S,3S)-ACPD also produced inhibitions in the carrageenan
      animals, in contrast to the mixed effects seen in normal animals. The group I
      agonist (S)-3,5-DHPG produced mixed effects (inhibitions and facilitations) in
      both normal and carrageenan animals. This in vivo study shows that the effects of
      metabotropic glutamate receptor agonists are more complex than in vitro studies
      have suggested to date.

PMID- 9653878
TI  - Adenosine A2 receptor mediation of pre- and postsynaptic excitatory effects of
      adenosine in rat hippocampus in vitro.
AB  - Excitatory effects of adenosine in the rat hippocampus were studied by
      intracellular recording from CA1 pyramidal cells in vitro. Application of 100
      microM adenosine induced a rapid hyperpolarization and a decrease in input
      resistance, and depressed the excitatory postsynaptic potentials (EPSPs) evoked
      by stimulation of Schaffer collaterals in all neurons tested. In 55% of the
      neurons this was followed by an excitation. This excitation consisted of a slow
      depolarization lasting 9 +/- 4.7 min, an increase in input resistance and an
      increase in the amplitude of the evoked EPSPs. This excitation could also be
      observed when synaptic transmission was prevented by 1 microM tetrodotoxin
      (tetrodotoxin). In the presence of 5 microM 8-(p-sulphophenyl)theophylline (8
      SPT) adenosine (10 microM) enhanced the amplitude of evoked EPSPs by 20% +/- 3.6
      (n = 5) in all neurons tested. Chloroadenosine (chloroadenosine; a stable analog
      of adenosine; 20 microM) induced a similar hyperpolarization associated with
      decrease in input resistance; this was followed by a similar excitation as seen
      with adenosine in 22 of the 27 neurons tested. L-baclofen (20 microM) induced a
      hyperpolarization associated with decrease in input resistance in all six neurons
      tested but an ensuing excitation was not observed. CGS 21680 (30 nM), a selective
      adenosine A2 receptor agonist, induced a slow depolarization associated with an
      increase in input resistance and, in 11 of 36 neurons, enhanced the amplitude of
      evoked EPSPs. These excitatory effects of CGS 21680 were blocked by the selective
      adenosine A2 receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX, 10
      microM). In the presence of 1 microM tetrodotoxin 30 nM CGS 21680 still produced
      a slow depolarization and an increase in input resistance. In addition, high
      doses of CGS 21680 (10 and 20 microM) depressed the amplitude of EPSPs evoked by
      stimulation of Schaffer collateral afferents, yet there was little effect on the
      resting membrane potential or input resistance despite the fact that 20 microM
      chloroadenosine caused a pronounced hyperpolarization associated with a decrease
      in input resistance in the same cell. These results indicate that the excitatory
      effects of adenosine may be mediated via activation of adenosine A2 receptors at
      both presynaptic and postsynaptic sites in the hippocampal CA1 region.

PMID- 9653879
TI  - Neuroprotection by novel antagonists at the NMDA receptor channel and glycineB
      sites.
AB  - Glutamate may act via an N-methyl-D-Aspartate (NMDA)-sensitive receptor site to
      destroy cholinergic neurons within the nucleus basalis magnocellularis in age
      associated neurodegenerative diseases. Multiple interesting properties of the
      NMDA receptor are relevant to its excitotoxic actions, e.g., glutamate is
      ineffective unless a glycine (gly) modulatory site is also occupied. Thus, the
      antagonism of glutamate receptor-related toxicity by blockade of either the NMDA
      sensitive recognition site or the gly binding site may therefore have therapeutic
      applications. The current study investigated the ability of four novel
      noncompetitive antagonists at these two sites: one NMDA open channel antagonist
      (MRZ 2/579: 1-amino-1,3,3,5,5-pentamethyl-cyclohexane hydrochloride), and three
      glyB receptor antagonists (MRZ 2/570: 8-bromo-4-hydroxy-1-oxo-1,2
      dihydropyridaziono [4,5-beta] quinoline-5-oxide choline salt; MRZ 2/57: 8-fluoro
      4-hydroxy-1-oxo-1,2-dihydropyridaziono [4,5-beta] quinoline-5-oxide choline; MRZ
      2/576: 8-chloro-4-hydroxy-1-oxo-1,2-dihydropyridaziono [4,5-beta] quinoline-5
      oxide choline) administered acutely, to provide neuroprotection from a NMDA
      receptor agonist within the nucleus basalis magnocellularis of young rats.
      Injection of NMDA into the nucleus basalis magnocellularis significantly
      decreased cortical choline acetyltransferase activity. Acute administration
      (i.p.) of MRZ 2/579, 2/570, 2/571 and 2/576 provided significant neuroprotection
      from NMDA.

PMID- 9653880
TI  - Presynaptic mGlu1 type receptors potentiate transmitter output in the rat cortex.
AB  - In the present study we used freely moving rats with a microdialysis probe placed
      in their parietal cortex to study the effects of local application of agonists
      and antagonists of metabotropic glutamate (mGlu) receptors on glutamate release.
      (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD; 0.1-1 mM), a non
      selective agonist of metabotropic glutamate (mGlu) receptors, increased glutamate
      concentration in the dialysate up to 3-fold. A significant increase in glutamate
      output in cortical dialysates was also obtained with (RS)-3,5
      dihydroxyphenylglycine (DHPG; 0.5-1 mM), a group 1-selective mGlu receptor
      agonist, suggesting the involvement of group 1 mGlu receptors in 1S,3R-ACPD
      effects. S-4-carboxyphenylglycine (S-4CPG; 0.3 microM), a mGlu1 receptor
      antagonist with a mild agonist action on mGlu2 receptors, antagonised, in a
      surmountable manner, the effects of 1S,3 R-ACPD. Similarly, 1-aminoindan-1,5
      dicarboxylic acid (AIDA; 0.03-1 mM) a selective group 1 antagonist with a
      preferential action on mGlu1 type receptors, antagonised the effects of 1S,3R
      ACPD. Finally, (S)-(+)-2-(3'-Carboxybicyclo[1.1.1]pentyl)-glycine (UPF596; 30-300
      microM), a potent mGlu1 antagonist with modest agonist activity on mGlu5,
      antagonised 1S,3R-ACPD-induced glutamate release. In conclusion, our data showed
      that 1S,3R-ACPD-induced glutamate release in the parietal cortex is mediated by
      mGlu1 receptors and that, under basal conditions, these receptors are not
      tonically activated.

PMID- 9653881
TI  - The gamma-aminobutyric acid uptake inhibitor NO-711 potentiates 3
      aminopropylphosphinic acid-induced actions in rat neocortical slices.
AB  - In rat neocortical slices maintained in Mg2+-free Krebs medium, the GABAB
      receptor agonists baclofen and 3-aminopropylphosphinic acid dose-dependently
      reduced the frequency of spontaneous discharges, 3-aminopropylphosphinic acid
      being 10 times less potent than baclofen. These were sensitive to the antagonist
      CGP 52432 (3-[[3,4-dichloro-phenyl)methyl]-amino]propyl](-P-diethoxymethyl)-
      phosphinic acid) (1, 5 and 10 microM). The GABA uptake inhibitor NO-711 (1-(2
      (((diphenylmethylene)amino)oxy)ethyl)-1,2,5,6-tetrahydro-3-+ ++pyridinecarboxylic
      acid) (5 and 10 microM) produced 2.9 and 9 fold increases in the potency of 3
      aminopropylphosphinic acid without affecting baclofen-induced responses. In this
      study, the low potency of 3-aminopropylphosphinic acid when compared to baclofen,
      may be attributed to its uptake by NO-711-sensitive GABA transporters.

PMID- 9653882
TI  - Alpha2-adrenoceptor antagonists enhance responses of dorsal horn neurones to
      formalin induced inflammation.
AB  - Intrathecally applied alpha2-adrenoceptor antagonists atipamezole, idazoxan and
      yohimbine had no significant effect on any neuronal response in normal animals.
      In contrast, all three antagonists (100 microg) significantly increased the area
      under the curve of the total response to formalin, especially the second phase.
      Our results suggest the alpha2-adrenoceptor-mediated noradrenergic inhibitory
      system in the spinal cord is dormant under normal conditions, but controls both
      the magnitude and duration of the neuronal responses to subcutaneous injection of
      formalin.

PMID- 9653883
TI  - Vasopressin mediates the inhibitory effect of central angiotensin II on
      cerebrospinal fluid formation.
AB  - Angiotensin II infused at low doses into the cerebral ventricles decreases
      cerebrospinal fluid (CSF) production. Since central angiotensin II also activates
      the sympathetic nervous system and promotes vasopressin release, the roles of
      these two factors in mediating the inhibitory effect of angiotensin II on CSF
      formation were studied. CSF production was measured in rats by the
      ventriculocisternal perfusion method. During central angiotensin II infusion (5
      pg min(-1)), the following adrenoceptor antagonists were administered
      intravenously (i.v.): phentolamine (alpha1/alpha2, 2 mg/kg per h), prazosin
      (alpha1, 1 mg/kg per h), and propranolol (beta, 1 mg/kg per h). None of these
      agents affected the inhibitory effect of angiotensin II on CSF formation. In
      comparison, in animals administered i.v., the vasopressin V1 receptor antagonist,
      d(CH2)5Tyr(Me)Arg-vasopressin (10 microg/kg per h), the angiotensin II-induced
      decrease in CSF production was abolished. Our observations indicate, therefore,
      that vasopressin mediates the inhibitory effect of central angiotensin II on CSF
      formation.

PMID- 9653884
TI  - In vivo microdialysis study of (+/-)-kavain on veratridine-induced glutamate
      release.
AB  - This is the first microdialysis study to address the effects of (+/-)-kavain on
      veratridine-induced glutamate release in freely moving rats. (+/-)-Kavain (100
      mg/kg, p.o.) significantly reduced veratridine-induced glutamate release compared
      with that of vehicle-treated controls. Maximum extracellular glutamate levels
      were obtained 20-40 min after veratridine stimulation (500 microM, added to the
      perfusate). In the control group the increase was 301% and in the (+/-)-kavain
      group the increase was significantly reduced to 219% (the basal value was 100%).
      These results demonstrate that (+/-)-kavain reduces veratridine-induced glutamate
      release in vivo, which confirms previous in vitro data.

PMID- 9653885
TI  - Involvement of nitrosothiols, nitric oxide and voltage-gated K+ channels in
      photorelaxation of vascular smooth muscle.
AB  - The effects of nitrosothiol depleting compounds (p-hydroxymercuribenzoate,
      iodacetamide and ethacrynic acid), a guanylyl cyclase inhibitor
      (1H[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, ODQ) and nitric oxide (NO) scavenger
      agents (xanthine/xanthine oxidase and 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl
      imidazoline-1-oxyl-3-oxide; carboxy-PTIO) on light-induced photorelaxation in rat
      thoracic aorta were investigated. Photorelaxation responses were decreased in the
      presence of nitrosothiol depleting compounds suggesting S-nitrosothiols as the
      tissue source of the NO, whereas reduction in photorelaxation by the guanylyl
      cyclase inhibitor and NO scavenger agents indicates involvement of both NO and
      cGMP in photorelaxation. In addition the sensitivity of photorelaxation to the
      voltage-gated potassium channel (KV) inhibitor, 4-aminopyridine, indicates that
      photorelaxation is mediated via a NO/cGMP-dependent, and, perhaps, direct light,
      activation of KV channels.

PMID- 9653886
TI  - Role of nitric oxide in post-ischemic cerebral hyperemia in anesthetized rats.
AB  - This study was undertaken to determine the extent to which nitric oxide (NO)
      mechanisms are involved in cerebral hyperemia following global brain ischemia.
      The vertebral arteries were cauterized through the first alar foramina in
      anesthetized male Sprague-Dawley rats and followed by 20-min occlusion of the
      common carotid arteries. Blood flow from the parietal cerebral cortex was
      measured using laser-Doppler flowmetry. In saline-treated animals, carotid
      occlusion reduced cerebral blood flow by approximately 95% with a maximal
      hyperemia of about 400% observed after 15 min of reperfusion. Pre-treatment with
      the nonspecific NO synthase inhibitor, L-NAME (NG-nitro-L-arginine methyl ester;
      2, 10 and 50 mg kg(-1)), produced dose-related depression of post-ischemic
      hyperemia, whereas D-NAME (10 mg kg(-1)) was inactive. Pre-treatment with L
      arginine (300 mg kg(-1), i.v.) prevented L-NAME attenuation of cerebral
      hyperemia. The selective neuronal NO synthase inhibitor, 7-nitroindazole (30 mg
      kg(-1)), was without significant depressant effect. These results suggest that NO
      (largely from vascular endothelium) is instrumental in development of post
      ischemic cerebral hyperemia.

PMID- 9653887
TI  - Relationship between the antithrombotic effect of YM-75466, a novel factor Xa
      inhibitor, and coagulation parameters in rats.
AB  - The relationship between the antithrombotic effects of intravenous infusions of
      YM-75466 [N-[4-[(1-acetimidoyl-4-piperidyl)oxy]phenyl]-N-[(7-amidino-2-naph
      thyl)methyl] sulfamoyl]acetic acid monomethanesulfonate), a novel factor Xa (FXa)
      inhibitor, and various coagulation parameters (prothrombin time, activated
      partial thromboplastin time, thrombin-antithrombin III complex (TAT), anti-FXa
      activity and anti-thrombin activity) in rats was studied and compared with
      results for heparin. In the arterio-venous shunt model, both agents exerted
      antithrombotic effects in a dose-dependent manner. Coagulation parameters were
      studied simultaneously with antithrombotic effects. YM-75466 did not prolong
      coagulation time even at the dose which exerted significant antithrombotic
      effects, while it decreased TAT level in plasma in a dose-dependent manner. YM
      75466 exerted anti-FXa activity but not anti-thrombin activity. In contrast,
      heparin prolonged activated partial thromboplastin time in a dose-dependent
      manner and decreased TAT level in plasma with increasing inhibition of thrombus
      formation. Heparin exerted both anti-FXa and anti-thrombin activity in a dose
      dependent manner. These results suggest that TAT is a suitable parameter for
      monitoring the antithrombotic effect of YM-75466 in the arterio-venous shunt
      model in rats and that YM-75466, unlike heparin, exerts its antithrombotic effect
      through specific inhibition of FXa without any effect on thrombin.

PMID- 9653888
TI  - Histamine receptor subtypes mediating hyperpolarization in the isolated, perfused
      rat mesenteric pre-arteriolar bed.
AB  - Histamine is a general dilator of rat blood vessels. We investigated the relative
      contribution of receptor subtypes to the rat mesenteric dilator responses
      initiated by histamine and related agonists. Histamine initiated dose, and
      endothelium-dependent, dilation of constricted mesenteric beds with an ED50 of
      0.4 +/- 0.1 nmol. The ED50 was increased 10-fold by 0.1 microM chlorpheniramine
      (a histamine H1-receptor selective antagonist). Histamine H2 receptor blockade
      with tiotidine (0.1 microM) slightly decreased, while thioperamide (1 microM), a
      selective histamine H3 receptor antagonist, did not block histamine-induced
      dilation. Mesenteric bed dilation initiated by histamine H2 receptor selective
      agonists, amthamine and dimaprit, were antagonized markedly by tiotidine.
      However, the dilation initiated by the putative histamine H3 receptor selective
      agonists, R(-)- or S(+)-alpha-methylhistamine and imetit were not affected by
      thioperamide (1 microM). Histamine H2- and H3-receptor mediated dilator effects
      were endothelium-independent and were blocked by either excess (80 mM)
      extracellular K+, or 1 mM tetrabutylammonium (a non-selective K+ channel
      blocker), as well as by 1 microM dequalinium, a non-peptide blocker of the small
      conductance Ca2+-activated (SKCa) K+ channels. We conclude that (i) histamine H1
      receptor subtype predominantly mediates endothelium-dependent dilator effect of
      histamine, and (ii) vascular hyperpolarization through opening of K+ channels
      (SKCa) mediate the dilator responses to histamine H2 receptor (amthamine and
      dimaprit) and the putative histamine H3 receptor (R(-)-alpha-methylhistamine and
      imetit) agonists.

PMID- 9653889
TI  - Acute and chronic neutral endopeptidase inhibition and the natriuretic response
      to acute volume expansion.
AB  - Neutral endopeptidase inhibition (NEPI) provides a potential avenue to modulate
      the actions of atrial natriuretic peptide (ANP). We tested the hypothesis that
      acute and chronic NEPI increased the renal responses at baseline and after acute
      volume expansion in rats. ANP plasma levels and cGMP excretion were significantly
      increased with acute NEPI by SQ 28.603, whereas chronic inhibition with SCH 34826
      did not lead to any changes. The ratio of cGMP excretion per plasma ANP, however,
      was significantly increased (6.2 +/- 0.9) by chronic treatment with SCH 34826
      compared to chronic vehicle treatment (4.2 +/- 0.7) indicating an activated renal
      ANP receptor system. Baseline diuresis and natriuresis were enhanced with acute
      but not with chronic treatment. After acute volume expansion, ANP increased five
      fold with acute NEPI, whereas it only increased about 70% in chronically
      inhibited rats. The natriuretic (497 +/- 62 vs. 329 +/- 42 micromol/60 min with
      vehicle, P < 0.05) and diuretic responses were significantly enhanced with
      chronic treatment. Together with an increased cGMP/ANP ratio, these data suggest
      that chronic activation of the renal ANP system after long-term NEPI facilitated
      the excretion of an acute volume load. These findings may have therapeutic
      implications in patients with chronic sodium retention.

PMID- 9653890
TI  - Antitussive effect of moguisteine on allergic coughs in the guinea pig.
AB  - The effect of moguisteine, a novel peripherally acting non-narcotic antitussive
      drug, on allergic coughs was examined in guinea pigs. Male Hartley guinea pigs
      were actively sensitized to ovalbumin. The number of coughs elicited over 5 min
      following a 2-min exposure to ovalbumin was counted. Exposure of sensitized
      guinea pigs to 0.5% ovalbumin aerosol induced 22.0 +/- 3.2 coughs/5 min.
      Moguisteine at doses of 30 and 56 mg/kg, p.o., dose-dependently and significantly
      suppressed the number of allergic coughs. Dihydrocodeine at doses of 30 and 56
      mg/kg, p.o., dose-dependently but not significantly reduced the number of
      allergic coughs. These results suggest that moguisteine may be of a therapeutic
      benefit in reducing allergic coughs.

PMID- 9653891
TI  - Airway hyperresponsiveness to histamine in mycoplasmal infection: role of
      histamine N-methyltransferase.
AB  - To elucidate the modulatory role of histamine-degrading enzymes in airway
      constrictor responses in mycoplasmal infection, we studied hamster tracheal
      segments under isometric conditions in vitro. Nasal inoculation with Mycoplasma
      pneumoniae potentiated the contractile responses to histamine but not to
      methacholine. Pretreatment of tissues with the histamine N-methyltransferase
      inhibitor SKF 91488 abolished the infection-induced potentiation, whereas, the
      diamine oxidase inhibitor aminoguanidine had no effect. The histamine N
      methyltransferase but not diamine oxidase activity in tracheal tissues was
      decreased in infected animals. These results suggest that M. pneumoniae causes
      airway hyperresponsiveness to histamine probably through a reduction of
      endogenous histamine N-methyltransferase activity.

PMID- 9653892
TI  - Capsaicin treatment induces muscarinic hyperreactivity in guinea pig trachea: a
      warning.
AB  - Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is a widely used tool for the
      depletion of neuropeptides from sensory C-fibres. Upon capsaicin treatment
      tachykinins are released, resulting in a variety of responses in the airways. We
      showed that after capsaicin (0.3 microM; 30 min) treatment of guinea pig tracheal
      smooth muscle preparations, the maximal contraction of the trachea after
      methacholine stimulation was strongly increased (capsaicin: 1.147 +/- 0.050 g vs.
      control: 0.717 +/- 0.047 g). This effect was completely nullified after
      pretreatment with capsazepine (2-[2-(4-chlorophenyl)ethyl-amino-thiocarbonyl]-7,8
      dihydroxy-2,3, 4,5-tetrahydro-1H-2benzazepine; a vanilloid receptor antagonist)
      and YM38336 (a dual tachykinin NK1 and tachykinin NK2 receptor antagonist). Our
      results serve as a warning against using capsaicin as a putatively clean
      pharmacological tool to deplete the neuropeptides from pools on the C-fibres
      because we showed that capsaicin also strongly influences basal mechanisms in
      tracheal smooth muscle control.

PMID- 9653893
TI  - Effects of ZD7114, a selective beta3-adrenoceptor agonist, on neuroendocrine
      mechanisms controlling energy balance.
AB  - Selective beta3-adrenoceptor agonists increase energy expenditure by increasing
      non-shivering thermogenesis in brown adipose tissue. The aim of this study was to
      investigate how changes in energy balance affect energy intake and interaction of
      peripheral metabolic feedback signals with central neuroendocrine mechanisms
      participating in the control of body energy balance. Expression of
      preproneuropeptide Y (preproNPY) mRNA in the arcuate nucleus and
      preprocorticotropin-releasing factor (CRF) mRNA in the paraventricular nucleus
      were measured by in situ hybridisation technique after 1 day, 1 and 5 weeks of
      treatment with ZD7114 ((S)-4-[2-[(2-hydroxy-3-phenoxypropyl)amino]ethoxy]-N-(2
      methoxyet hyl)phenoxyacetamide, 3 mg kg(-1) day(-1) in drinking water) in obese
      fa/fa Zucker rats. In addition, expression of leptin mRNA in epididymal fat and
      serum levels of leptin were analysed. Food intake, body weights, binding of GDP
      to brown adipose tissue mitochondria, plasma insulin and glucose were also
      measured. Treatment with ZD7114 significantly reduced weight gain and activated
      brown adipose tissue thermogenesis, but had no effect on food intake. Expressions
      of preproNPY or preproCRF mRNAs were similarly not changed by treatment with
      ZD7114. Furthermore, ZD7114 had no effect on plasma insulin or leptin and the
      expression of leptin mRNA in epididymal fat. However, statistically significant
      correlations were found between preproNPY and preproCRF mRNA expressions and
      brown fat thermogenic activity and plasma insulin levels in the ZD7114 treated
      rats, but not in the control rats. It is concluded that treatment with ZD7114
      markedly activated brown fat thermogenesis, but did not affect neuropeptide Y
      (NPY) and CRF gene expression per se. However, the correlation analyses suggest
      that ZD7114 may modulate feedback connections of brown adipose tissue
      thermogenesis and plasma insulin with the hypothalamic neuroendocrine mechanisms
      integrating body energy balance.

PMID- 9653894
TI  - Effects of calcitonin gene-related peptide-(8-37) on withdrawal responses in rats
      with inflammation.
AB  - The present study was performed to explore the effect of subcutaneous injection
      of carrageenan into the rat plantar region on hindpaw edema formation and the
      latency of hindpaw withdrawal to presumed nociceptive stimulation. Subcutaneous
      injection of carrageenan into the left hindpaw induced a significant increase in
      the volume of the left hindpaw, leaving the right side unaffected. In addition,
      we found a bilateral decrease in hindpaw withdrawal latency to heat and
      mechanical, but not to cold stimulation. The decreased bilateral hindpaw
      withdrawal latency to heat stimulation lasted for 14 days after carrageenan
      injection. The decreased bilateral hindpaw withdrawal latency to mechanical
      stimulation lasted for 2 days after the injection, then reversed and increased
      from day 3 to 14. Intrathecal injection of either 10 nmol of calcitonin gene
      related peptide 8-37 or 26.6 nmol of morphine induced significant bilateral
      increases in hindpaw withdrawal latency, which were more pronounced with the
      morphine. The results show that experimentally induced unilateral hindpaw
      inflammation induces a bilateral decrease in hindpaw withdrawal latencies to
      presumed nociceptive stimulation while the sensory systems for heat and
      mechanical stimulation were differently affected after carrageenan injection.

PMID- 9653895
TI  - Effect of hypolipidemic drugs on key enzyme activities related to lipid
      metabolism in normolipidemic rabbits.
AB  - The effect of atorvastatin (3 mg kg(-1) day(-1)), simvastatin (3 mg kg(-1) day(
      1)) and bezafibrate (100 mg kg(-1) day(-1)) administered for 4 weeks to male New
      Zealand white rabbits on enzyme activities related to lipid metabolism has been
      studied. Only the statins reduced plasma cholesterol values, while none of the
      drugs modified plasma triglyceride or high density lipoprotein (HDL)-cholesterol
      concentrations, nor the activity of enzymes such as hepatic diacylglycerol
      acyltransferase, lipoprotein lipase or hepatic lipase, directly involved in
      triglyceride metabolism. Both statins elicited similar increases in the hepatic
      microsomal 3-hydroxy-3-methyl-glutaryl Coenzyme A (CoA) reductase activity (147
      and 109% induction for simvastatin and atorvastatin, respectively), and none of
      the drugs assayed modified hepatic acyl-coenzyme A:cholesterol acyltransferase
      activity significantly. Only bezafibrate induced a significant 57% reduction in
      the activity of hepatic microsomal cholesterol 7alpha-hydroxylase. Regarding the
      rate limiting enzyme of phosphatidylcholine biosynthesis, CTP:phosphocholine
      cytidylyl transferase, atorvastatin and bezafibrate behaved similarly, decreasing
      the enzyme activity in the liver by 45% and 54%, respectively; simvastatin
      induced no modification of this activity. The reduction of CTP:phosphocholine
      cytidylyl transferase activity is not caused by a direct inhibition of the enzyme
      by bezafibrate and atorvastatin. Further, the inhibitory effect of atorvastatin
      appears to be unrelated to the inhibition of 3-hydroxy-3-methyl-glutaryl CoA
      reductase elicited in vivo.

PMID- 9653896
TI  - Are high-affinity progesterone binding site(s) from porcine liver microsomes
      members of the sigma receptor family?
AB  - Membrane progesterone binding sites have been purified recently from pig liver.
      Since progesterone is considered as an endogenous sigma (sigma) receptor ligand,
      these sites were characterized pharmacologically by ligands selective for sigma
      receptor and dopamine receptor binding sites, and by other drugs from distinct
      pharmacological classes. Binding studies using the radioligand [3H]progesterone
      were done in crude membrane preparations and solubilized fractions to determine
      half-maximal inhibitory concentration (IC50) values, from which inhibitory
      constants (Ki values) were calculated. Radioligand binding was inhibited by the
      sigma receptor ligands haloperidol, carbetapentane citrate, 1,3-Di(2
      tolyl)guanidine (DTG), R(-)-N-(3-phenyl-1-propyl)-1-phenyl-2 aminopropane HCl (R(
      )-PPAAP HCl), or sigma receptor antagonists like (+)-3-(3-hydroxyphenyl)-N
      propylpiperidine HCl (R(+)-PPP HCl) and cis-9-[3-(3,5-dimethyl-1
      piperazinyl)propyl]-9H-carbazole dihydrochloride (rimcazole 2HCl). The hierarchy
      of inhibitory action was not fully compatible with either sigma receptor class I
      (moderate affinity of pentazocine, diphenylhydantoin (phenytoin) insensitivity)
      or II sites (high affinity of carbetapentane). The data thus suggest that
      progesterone binding sites in porcine liver membranes are related to the sigma
      receptor binding site superfamily, but may represent a particular species with
      progesterone specificity.

PMID- 9653897
TI  - Characterization of alpha1-adrenoceptor subtypes in the pig.
AB  - The identities of the alpha1-adrenoceptor subtypes present in various tissues of
      the pig were studied using [3H]prazosin radioligand binding. The subtypes were
      characterized by performing competition experiments for various subtype selective
      drugs. In the cerebral cortex, spleen and heart, both alpha1A- and alpha1B
      adrenoceptors were detected. In the liver was found only the alpha1A-subtype,
      while in the aorta was found only the alpha1B-subtype. An alpha1-adrenoceptor
      subtype was present in the adrenal gland with a high affinity for prazosin, the
      pKd value being 9.6, but with relatively low affinities for other alpha1
      adrenoceptor binding drugs. The adrenal gland alpha1-adrenoceptor did not seem to
      represent the classical alpha1D-subtype, since drugs selective for the alpha1D
      subtype in other species, including BMY7378 and SKF104856, showed low affinities
      for the pig adrenal gland alpha1-adrenoceptor.

PMID- 9653898
TI  - Polyamine-like actions of aminoglycosides and aminoglycoside derivatives at NMDA
      receptors.
AB  - Recent pharmacological studies indicate that aminoglycoside-induced hearing loss
      may be an excitotoxic process modulated by a polyamine-like activation of
      cochlear NMDA receptors. Aminoglycoside antibiotics are constituted by a series
      of glycosidically linked aminocyclitols and aminosugars. We report here on the
      actions of these individual aminocyclitols and aminosugars on wild type NMDA
      receptors from rat brain. Compared to the parent molecules, neither
      aminocyclitols (e.g., 2-deoxystreptamine, streptamine, and streptidine) nor
      aminosugars (e.g., D-glucosamine and kanosamine) were effective at enhancing
      [3H]dizocilpine ([3H]MK-801) binding or inhibiting [3H]ifenprodil at NMDA
      receptors. Moreover, the appropriate combinations of aminosugars and
      aminocyclitols did not reconstitute the activity of the parent aminoglycoside at
      NMDA receptors. These data indicate that the polyamine-like actions of
      aminoglycosides are attributable to the conformation of the parent molecule
      rather than a particular amine containing constituent. Thus, it may be possible
      to synthesize or isolate aminoglycoside antibiotics devoid of ototoxicity.

PMID- 9653899
TI  - Kinetics of alkylation of cloned rat alpha1-adrenoceptor subtypes by
      chloroethylclonidine.
AB  - We quantified and compared the rates at which chloroethylclonidine (CEC)
      inactivated cloned rat alpha1A, alpha1B-, and alpha1D-adrenoceptors. Membranes
      from cells transfected with one of the three cloned alpha1-adrenoceptors were
      incubated for various intervals with 100 microM chloroethylclonidine at 10
      degrees C, 25 degrees C or 37 degrees C. The fraction of receptors alkylated by
      chloroethylclonidine was determined by [3H]prazosin binding. Chloroethylclonidine
      fully inactivated each alpha1-adrenoceptor subtype via a first order reaction.
      Alkylation by chloroethylclonidine was markedly slower for the alpha1A
      adrenoceptor vs. the other two subtypes (rate constants in 10(-3) min(-1) at 10
      degrees C: 0.99 +/- 0.01 (alpha1A), 7.26 +/- 0.15 (alpha1B), and 7.01 +/- 0.12
      (alpha1D)). Despite differences in rate, activation energies for alkylation were
      similar among subtypes. suggesting a similar binding sites for
      chloroethylclonidine. Computer simulations of kinetic data in mixed receptor
      populations and experiments with membranes from rat brain showed that nonlinear
      curve fitting could distinguish relative proportions of alpha1A-adrenoceptor vs.
      the other two subtypes. We conclude that measurement of the rate of alkylation by
      chloroethylclonidine, rather than the total amount of alkylation, is most useful
      in distinguishing the relative proportion of alpha1A-adrenoceptor in tissues.

PMID- 9653900
TI  - Pericardial mesothelial cells produce endothelin-1 and possess functional
      endothelin ETB receptors.
AB  - We investigated the endothelin production and endothelin receptor activity of
      pericardial mesothelial cells obtained from spontaneously hypertensive rats (SHR)
      and Wistar-Kyoto (WKY) rats. The pericardial mesothelial cells were maintained in
      vitro and the production of endothelin-1 by these cells was evaluated by using a
      sensitive sandwich-type enzyme immunoassay for endothelin-1 and big endothelin-1.
      Endothelin receptor subtypes were pharmacologically analyzed by measuring the
      changes of intracellular Ca2+ concentration ([Ca2+]i) in pericardial mesothelial
      cells. Mesothelial cells from both strains produced more immunoreactive
      endothelin-1 than big endothelin-1. The production of immunoreactive endothelin-1
      progressively increased in a culture time-dependent manner. The amount of
      immunoreactive endothelin-1 detected after 72 h in pericardial mesothelial cells
      of SHR was significantly (P < 0.05) higher than that in the cells of WKY rats
      (SHR: 196.7 +/- 19.1 pg/10(6) cells; WKY: 122.7 +/- 10.6 pg/10(6) cells).
      Endothelin-1 and endothelin-3 induced elevation of [Ca2+]i in pericardial
      mesothelial cells. The selective agonist of the endothelin ETB receptor,
      sarafotoxin S6c, also induced elevation of [Ca2+]i. The endothelin- and
      sarafotoxin S6c-induced elevations of [Ca2+]i in pericardial mesothelial cells
      from SHR were greater than those in mesothelial cells from WKY rats. The
      endothelin ETB receptor antagonist, IRL 1038 ([Cys11,Cys15]endothelin-1-(11-21)),
      significantly inhibited the endothelin-1- and endothelin-3-induced changes in
      [Ca2+]i. The endothelin ETA receptor antagonist, FR 1393171 ((R)2-[(R)-2-[(S)-2
      [[1-(hexahydro-1H-azepinyl)]carbonyl]ammino -4-methylpentanoyl]amino-3-[3-(1
      methyl-1H-indoyl)]propio nyl]amino-3-(2-pyridyl)propionic acid), did not affect
      these changes. From these results, pericardial mesothelial cells from both SHR
      and WKY rats shared the ability to produce endothelin-1 spontaneously in culture,
      although consistently greater production was detected in cultures of SHR origin.
      Moreover, pericardial mesothelial cells of SHR origin may have increased numbers
      of endothelin ETB receptors and/or a more active signal transduction system
      compared with those of WKY rats. These results suggest that endothelin-1 may play
      an important role in the pericardium in an autocrine and/or paracrine fashion.

PMID- 9653901
TI  - Evidence that angiotensin II, endothelins and nitric oxide regulate mitogen
      activated protein kinase activity in rat aorta.
AB  - We measured the activity of mitogen-activated protein (MAP) kinases, enzymes
      believed to be involved in the pathway for cell proliferation, in rat aortic
      strips with or without endothelium, and examined effects of angiotensin receptor
      antagonists, endothelin receptor antagonists and nitric oxide (NO)-related
      agents. Endothelium removal produced an activation of MAP kinase activity in the
      strips, whereas the enzyme activity was not affected in the adventitia. The MAP
      kinase activation was inhibited by either the angiotensin AT1 receptor antagonist
      losartan or the endothelin ETA receptor antagonist BQ 123. The combination of
      both antagonists caused an additive inhibition. The angiotensin AT2 receptor
      antagonist PD 123,319 and the endothelin ETB receptor antagonist BQ 788 did not
      affect the MAP kinase activation. The NO synthase inhibitor NG-nitro-L-arginine
      methyl ester (L-NAME) caused an activation of MAP kinase in the endothelium
      intact aorta and the MAP kinase activation was inhibited by losartan or BQ123.
      The NO releaser nitroprusside inhibited the MAP kinase activation induced by
      endothelium removal or angiotensin II. These results suggest that even in
      isolated arteries, NO of endothelial origin tonically exert MAP kinase-inhibiting
      effects and endogenous angiotensin II and endothelins in the media are tonically
      released to cause MAP kinase-stimulating effects in medial smooth muscle.

PMID- 9653902
TI  - Absence of association between delta and gamma2 subunits in native GABA(A)
      receptors from rat brain.
AB  - We investigated the possible association between delta and gamma2 subunits in
      native GABA(A) receptors, from different rat brain regions, using subunit
      specific anti-delta and anti-gamma2 antibodies. Previous reports have provided
      somewhat controversial results, indicating both the presence and the absence of
      association between these two subunits in native receptors. Our results indicate
      the absence of co-localization between delta and gamma2 subunits. In
      immunoprecipitation experiments, anti-delta antibody consistently
      immunoprecipitated [3H]muscimol binding activity (GABA binding sites) from all
      brain areas tested (10-20% of the total binding). However, under the same
      conditions, no significant [3H]flumazenil or [3H]ethyl 8-azido-6-dihydro-5-methyl
      6-oxo-4H-imidazol[1,5-a]-[1,4]benzodiazepine- 3-carboxylate (Ro15-4513) binding
      (benzodiazepine binding sites) activity was detected in the immunopellets. These
      results indicate the absence of association between delta and gamma2 subunits.
      This question was directly addressed by immunopurification and Western blot
      experiments. As expected, no gamma2 subunits were detected in anti-delta
      immunoaffinity purified receptors. Conversely, no delta subunits were identified
      in anti-gamma2 immunopurified receptors. Thus, these results demonstrate the
      absence of association between delta and gamma2 subunits in native GABA(A)
      receptors. Finally, our results also indicate the relevance of the solubilization
      conditions on the apparent association between different subunits of the native
      GABA(A) receptor complex.

PMID- 9653903
TI  - Cyclic GMP inhibits cytoplasmic Ca2+ oscillation by increasing Ca2+-ATPase
      activity in rat megakaryocytes.
AB  - The regulatory effects of cyclic GMP on purinoceptor-operated cytoplasmic Ca2+
      oscillation of rat megakaryocytes were investigated by using whole-cell patch
      clamp technique. ATP-induced oscillatory K+ currents though Ca2+-activated K+
      channels (I(KCa)S) were depressed by pretreatment with the guanylate cyclase
      activator, sodium nitroprusside, and a stable membrane-permeable cGMP analogue, 8
      bromo-cGMP. The inhibition by sodium nitroprusside was blocked by treatment with
      a cyclic nucleotide-dependent protein kinase inhibitor, N-[2-(methylamino)]-5
      isoquinolinesulfonamide x HCl (H-8) (10 microM), but not by a selective cAMP
      dependent-protein kinase inhibitor, Rp-cAMPS (100 microM). The oscillatory I(KCa)
      directly evoked by intracellular D-myo-inositol-trisphosphate (IP3) perfusion was
      also inhibited by the application of sodium nitroprusside. The inhibitory effect
      of sodium nitroprusside disappeared when the ATP-induced oscillatory I(KCa) was
      changed to a monophasic sustained I(KCa) current by inhibition of Ca2+-ATPase.
      These results suggested that cGMP depressed Ca2+ mobilization by improving Ca2+
      ATPase activity by phosphorylation.

PMID- 9653904
TI  - Foetal erythrocytes exhibit an increased ability to scavenge for nitric oxide.
AB  - The presence of adult human whole blood inhibited in vitro relaxations of rat
      aortic rings by the nitric oxide (NO) donor S-nitroso-N-acetyl-DL-penicillamine
      (SNAP). Incubation with foetal blood containing the same concentration of
      haemoglobin produced a shift to the right of the relaxation curve. SNAP-induced
      vasorelaxations were more inhibited by dialysed solutions of haemoglobin than by
      the presence of erythrocytes in the organ bath, but there were no differences
      between the effect of adult or foetal haemoglobins. The presence of plasma from
      adult or foetal blood did not modify the effects of SNAP. Relaxations induced by
      endogenous, endothelium-derived, NO were more inhibited by foetal than by adult
      erythrocytes. These results suggest that foetal erythrocytes have a higher NO
      scavenging effect than those present in adult blood.

PMID- 9653907
TI  - Human vaginal mucosal immune system: characterization and function.
AB  - OBJECTIVE: The mucosal immune system has been recognized as the first line of
      defense against foreign antigens. The limited information available on the
      mucosal immunity of the lower reproductive organs have restricted our ability to
      fight infections, especially, the sexually transmitted disease. The aim of this
      study was to characterize in-vitro the human vaginal lamina propria lymphocytes
      (VLPL), their cell surface phenotypes, and cellular function. METHODS: VLPL were
      isolated from human vaginal mucosa by enzymatic techniques. Cell surface
      characteristics were investigated by immunohistochemistry and flow cytometric
      analysis. Cellular immune function was evaluated by 3H-thymidine incorporation
      studies and ornithine decarboxylase (ODC) activity. RESULTS: Immunohistochemistry
      and flow cytometric analysis showed that the CD4/CD8 ratio of the human vaginal
      mucosa is reversed compared to the gut lamina propria lymphocytes (0.55 +/-
      0.17). PHA and ConA mitogens enhanced VLPL thymidine incorporation, while PWM did
      not have any significant effect. Very high level of ODC activity was observed in
      VLPL after PHA stimulation. CONCLUSIONS: The human VLPL can be isolated,
      characterized, and respond to a mitogenic stimulus. We postulate that further
      analysis of the vaginal immune system will enhance our understanding of local
      defence mechanisms which will help in the development of new therapeutic
      modalities against vaginal infections.

PMID- 9653906
TI  - Proliferative activity, p53 accumulation and neoangiogenesis in pulmonary
      carcinosarcomas and pulmonary blastomas.
AB  - Carcinosarcoma and pulmonary blastomas are rare biphasic tumors. Lung cancer
      pathogenesis is a multistep process. Proliferative activity, p53 accumulation and
      angiogenesis are of well-known relevance and ought to be evaluated in the
      epithelial and mesenchymal components of these tumors. Using antibodies against
      Ki-67 epitope MIB1 and proliferating cell nuclear antigen (PC 10) in 10
      carcinosarcomas, tumors revealed a significantly higher proliferative activity in
      the epithelial component compared with the mesenchymal component in the MIB1
      reaction (p = 0.013). In three pulmonary blastomas of the biphasic subtype,
      proliferative activity was similar in both parts. In five of 10 carcinosarcomas
      and in one of three pulmonary blastomas, accumulation of the p53 epitopes Pab
      1801 and/or DO-1 was found. At the tumor front, a significantly higher vessel
      density was found compared with the central parts (p < or = 0.015) using a
      monoclonal antibody against human endothelium (CD 31). No differences were found
      between carcinosarcomas and pulmoblastomas. Higher proliferative activity in
      carcinosarcomas revealed a better prognosis regarding metastasis behavior (p =
      0.05) and tumor-associated death in the follow-up (p < or = 0.017). p53
      accumulation and microvessel density were of no prognostic value. This is in
      contrast to results in non-small cell lung cancer, pointing to a different
      biologic behavior.

PMID- 9653908
TI  - Prognostic assessment of histologic parameters in breast carcinomas: a
      prospective study.
AB  - A group of 350 unselected breast cancer patients, treated at the Center of
      Oncology in Cracow, Poland, between January 1992 and December 1994, was analyzed.
      The following reciprocally interrelated histologic characteristics were
      evaluated: 1) histologic tumor type (considered in 3 categories of aggressivity),
      2) tumor grade (according to Scarf-Bloom-Richardson), 3) constituent of in-situ
      carcinoma in invasive cancers and characterization of breast lobuli, 4) tumor
      growth pattern (microfocal, macrofocal or mixed), 5) invasion of nerves, 6)
      vascular invasion by cancer cells in tumor surroundings, 7) extensiveness of
      tumor necrosis, 8) involvement of the breast distant from the tumor mass by
      cancer cells, 9) status of axillary lymph nodes, 10) invasion of metastatic lymph
      node surroundings. Metastases in axillary lymph nodes were independently
      influenced by vascular invasion in tumor surroundings and tumor diameter. The
      disease-free survival was independently influenced by tumor diameter, necrosis
      and stage of the disease (pTNM), whereas total survival related to tumor
      diameter, nodal status, microfocal pattern of tumor growth, vascular invasion and
      involvement of breast by cancer distant from the tumor mass was independently
      influenced only by tumor stage (pTNM).

PMID- 9653909
TI  - Chronic nonspecific endometritis.
AB  - To assess the proliferative activity of glands and stroma in nonspecific chronic
      endometritis (NCE), we evaluated the plasma and morphologic features. We examined
      25 endometrial sections that were coded as inactive for the morphologic features
      of NCE other than plasma cells and 25 proliferative endometria (PE) as controls.
      Furthermore, the sections were stained with methyl green pyronin (MGP) to
      demonstrate plasma cells and proliferative cell nuclear antigen (PCNA) for
      proliferative activity. The number of plasma cells and the grade of proliferative
      activity were determined by a semiquantitative scale. The results were compared
      by using the Mann-Whitney-U-test. Of the 25 inactive endometria cases, 11 were
      NCE and 14 were either early proliferative endometria (seven cases), lower
      uterine segments (five cases), or under hormone effect (two cases). The number of
      plasma cells in NCE was significantly higher than in PE. However, there were
      cases of NCE without plasma cells and cases of PE containing plasma cells.
      Proliferative activity was significantly lower in NCE cases than in the PE group
      (p < 0.05). The diagnosis of NCE should rely more on morphologic abnormalities
      than on plasma cell criteria. Identification of plasma cells may be useful for
      diagnosis.

PMID- 9653910
TI  - Frequency of endocervical cells in cervical smears and hysterectomy rate of the
      patients.
AB  - In gynecologic cytology, different reporting schemes suggest mentioning the
      presence of endocervical cells or asking for a statement on adequacy. We were
      interested in the question whether our data could provide a possible basis for
      discussing a sampling technique with smear takers. At the time of writing, in all
      cases, both the presence of endocervical cells and hysterectomy are recorded in
      our laboratory information system. Most smears are taken with cotton swabs, but
      the sampling technique is often modified according to the clinical situation. In
      a series of 20,471 cervical/vaginal smears, 2,152 (10.5%) were taken from
      hysterectomy patients. Among the non-hysterectomy patients, endocervical cells
      were found in 65% of the cases. Typically, there was a lower frequency of
      endocervical cells in smears stemming from older women. The frequency decreased
      from a maximum of 75% in the age group of 40-44 years to 45% in the age group of
      65-69 years. With regard to the smear takers, some differences were evident, with
      age distribution and frequency of hysterectomy being different among the smear
      takers. In a setting where many smears of hysterectomized patients are examined
      by cytology, good data quality is required to evaluate the sampling techniques of
      different smear takers. The age dependence of endocervical cell yield is
      confirmed. Different age distribution of the patients from different smear takers
      suggests that the percentage of smears showing endocervical cells cannot be
      considered an optimal estimator.

PMID- 9653911
TI  - Quantitative analysis of HLA DR expression and lymphocytic infiltrate in
      laryngeal cancer including clinical and morphological correlations.
AB  - HLA DR antigen expression in tumor cells and lymphocytic infiltrates at the
      tumour periphery were investigated in 68 laryngeal carcinomas. The tissue
      sections were studied by a quantitative method using computer image analysis
      system. The highest number of CD45RO+ cells was observed in the groups of the
      lowest clinical stage. There were statistically significant differences between
      the groups in the number of T cells, whereas no differences were found in HLA DR+
      cancer cell number, B cell number or mitosis count. Statistical analysis revealed
      a significant correlation between T-cell number at the periphery of the tumour
      and the number of cancer cells showing HLA DR expression. The results of the
      analysis, using Cox proportional hazard model with selected factors, showed that
      only HLA DR expression in cancer cells had a significant effect on survival,
      whereas the number of CD45RO+ and CD20+ cells, histological grade and mitosis
      count did not contribute further to prognostic information. To our knowledge,
      this is the first time that HLA DR expression and its correlation with
      lymphocytic infiltration have been shown by a quantitative method in laryngeal
      cancer.

PMID- 9653912
TI  - Stereological estimation of mean nuclear volume and staining pattern of Ki-67
      antigen in keratoacanthomas and squamous cell carcinomas.
AB  - Keratoacanthomas and squamous cell carcinomas of the skin share many
      histopathologic features, making differential diagnosis difficult. The aim of
      this study is to investigate the staining pattern of proliferating cells in
      keratoacanthomas and squamous cell carcinomas of the skin and to evaluate the
      value of nuclear morphometric criteria in differential diagnosis. Mean nuclear
      volume was assessed in 21 keratoacanthomas and 21 squamous cell carcinomas in
      tissue sections by a stereologic method. Immunohistochemical expression of Ki-67
      monoclonal antibody was assessed and the distribution pattern (random or
      peripheral) of proliferating cells evaluated. Mean nuclear volume (MNV +/- SD)
      was 590 +/- 293.0 for squamous cell carcinomas and 615 + 305.9 for
      keratoacanthomas. Statistical analysis showed no significant differences between
      both groups (p = 0.78) in terms of mean nuclear volume values. Proliferating
      cells in keratoacanthomas showed a peripheral distribution, whereas there was a
      random distribution of proliferating cells in squamous cell carcinomas. Our
      results indicate that quantitative nuclear features are not helpful in making a
      differentiation between keratoacanthomas and squamous cell carcinomas, while
      immunohistochemistry with Ki-67 antibody may give useful additional information
      in differential diagnosis.

PMID- 9653913
TI  - Atherosclerotic lesions, myocardial damage and lipidograms: a multiarterial study
      applying an atherometric system and canonical correlation.
AB  - 472 autopsy subjects were examined with the following aims: to study the
      association pattern of atherosclerotic lesions between different arterial
      sectors, the impact of serum lipid disorders (total cholesterol, HDL-c, LDL-c,
      VLDL-c, and triglycerides were analyzed) and the association pattern between the
      atherosclerotic lesions in different arterial sectors and the degree of heart
      damage. For morphometric analysis of the vessels (aorta, circle of Willis,
      coronary, renal, iliac, and femoral arteris) the atherometric system was used.
      The most relevant results were as follows: the lipid disorders show their
      greatest impact in the heart, coronary and femoral arteries and abdominal aorta,
      whereas the strongest correlations between the atherosclerotic lesions in
      different arterial sectors were found in those with anatomical continuity.

PMID- 9653914
TI  - Primary malignant lymphoma of the kidney: case report and literature review.
AB  - We report on a 65-year-old white woman who was hospitalized because of symptoms
      of an acute adrenocortical insufficiency. A CT scan revealed the presence of a
      large mass in the left kidney that infiltrated the adrenal gland. Fine needle
      aspiration cytology of the mass under imaging control failed to achieve a correct
      diagnosis, and nephrectomy was undertaken with a preoperative diagnosis of renal
      cell carcinoma. However, the frozen section reveals a neoplasm of large lymphoid
      cells with a diffuse growth pattern. Immunohistochemistry confirms the B-cell
      nature of the neoplasm (CD20+). The final diagnosis was non-Hodgkin B-cell high
      grade centroblastic lymphoma (KIEL classification). Postoperative studies failed
      to show lymph node or bone marrow infiltration by neoplastic cells. We found
      reports on only 60 malignant lymphomas, considered to be primary to the kidney.
      They usually affect middle-aged people, can be diagnosed with imaging techniques,
      and seem to show a better prognosis than other types of lymphoma.

PMID- 9653915
TI  - Sarcomatoid carcinoma (carcinosarcoma) of the gallbladder.
AB  - We report a case of carcinoma of the gallbladder in a 67-year-old woman. The
      description comprises the histological, immunohistochemical, ultrastructural and
      cytogenetical picture of the tumor. The ultrastructural features as well as
      chromosomal changes may denote the epithelial derivation of the tumor studied.

PMID- 9653916
TI  - Concurrence of localized Castleman's disease and peripheral small B-Lymphocytic
      lymphoma within the same lymph node.
AB  - Castleman's disease, also known as benign giant lymph node hyperplasia, is a
      lymphoproliferative disorder which can occur either in a localized or
      multicentric form. The latter is characterized by the development of malignant
      lymphoma, Kaposi's sarcoma or carcinoma in 32% of cases. By contrast, localized
      Castleman's disease has exceptionally been reported in association with non
      Hodgkin's lymphoma and - to the best of our knowledge - never at the same
      anatomic site. Here we describe the occurrence in the same lymph node of
      localized Castleman's disease (with monotypic plasma cell component) and an
      apparently unrelated peripheral small B-lymphocytic lymphoma.

PMID- 9653917
TI  - Spindle cell hemangioendotheliomas associated with multiple skeletal
      enchondromas: a variant of Maffucci's syndrome.
AB  - An unusual case of Maffucci's syndrome confined to an extremity with an
      additional superficial lymphangioma in the same limb is described. The patient, a
      47-year-old woman, presented with several painful subcutaneous spindle cell
      hemangioendotheliomas (SCHs) and multiple lytic bone lesions, some calcified, in
      the left leg. She has been followed for two years and continues to do well. The
      combination of SCHs and multiple enchondromas (ENCHs) should be searched in any
      patient who presents with SCHs or multiple ENCHs, because there is a significant
      risk of malignant transformation.

PMID- 9653918
TI  - Solitary neurofibroma of the gallbladder. A case report and review of the
      literature.
AB  - Benign non-epithelial neoplasms of the gallbladder are rare. A case of incidental
      neurofibroma of the gallbladder in a 44-year-old man without neurofibromatosis 1
      is reported. The intramural tumor, located in the neck of the gallbladder, was
      associated with lithiasis, chronic cholecystitis and localized fundic
      adenomyomatosis. Seven cases including the present one are reviewed. The seven
      patients ranged in age from 44 to 77 years, with an average age of 61.6 years.
      Four of the seven patients were women. Five tumors appeared as mural nodules, and
      two showed intraluminal growth. The most common location was the body of the
      gallbladder. The size of the lesion varied from 0.3 to 5.3 cm, with a mean size
      of 1.3 cm. Five of the seven cases were incidentally found in a gallbladder
      resected for cholelithiasis. Using ultrasonography, two cases with no lithiasis
      were detected preoperatively, presenting as intracavitary growing lesions by
      ultrasonography. It is possible that neurofibroma of the gallbladder may be more
      common than the small number of known cases indicates.

PMID- 9653919
TI  - Osseous manifestation of Rosai-Dorfman disease (sinus histiocytosis with massive
      lymphadenopathy). A case report and review of the literature.
AB  - Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy) is an
      unusual form of histiocytic disorder. Bone lesions are infrequent. We describe a
      33-year-old man with involvement of multiple bones but without lymphadenopathy at
      the time of presentation. The literature on osseous manifestation in this
      condition is reviewed.

PMID- 9653920
TI  - Gradient high-performance liquid chromatographic analysis of enkephalin peptides,
      their metabolites, and enzyme inhibitors using combined ultraviolet and
      electrochemical detection II. Application to ocular permeability studies in
      vitro.
AB  - A gradient HPLC method with combined ultraviolet (UV) and electrochemical
      detection (ED) was used to study the ocular permeability of [D-Ala2]-methionine
      enkephalinamide (MEA) in vitro. Coulometric ED was selective for MEA and its
      tyrosine-containing metabolites with quantitation limits between 20 and 60 nM
      (1.0-3.0 pmol per 50-microl injection), whereas UV detection at 205 nm allowed
      the determination of several aromatic metabolites and enzyme inhibitors with
      quantitation limits between 40 and 500 nM (2.0-25.0 pmol). This method was
      capable of detecting permeability of MEA and metabolite formation in the cornea
      and conjunctiva in vitro. Furthermore, effects of aminopeptidase inhibitor
      bestatin and enkephalinase inhibitor SCH 39370 on permeation and metabolism of
      MEA could be determined.

PMID- 9653921
TI  - Determination of melatonin in rat pineal, plasma and retina by high-performance
      liquid chromatography with electrochemical detection.
AB  - A sensitive method for the routine measurement of endogenous melatonin (MEL) in
      pineal, retina and plasma rat tissues has been developed using reversed-phase
      high-performance liquid chromatography with electrochemical detection.
      Quantification limit for MEL was 0.2 ng/mg protein in pineal, 15 pg/ml in plasma
      and 2.0 pg/mg protein in retina. To improve both MEL quantification and the
      reproducibility of the assay, an internal standard was used when an extraction in
      organic solvent was required, in contrast with other available chromatographic
      methods. MEL values and the circadian profile obtained in this study from both
      rat pineal and plasma agree with those reported previously. This method allows
      MEL detection in mammal retina, particularly in rat, where MEL levels are very
      low.

PMID- 9653922
TI  - Chromatographic separation of fluorescent thiol adducts of 4-chloro-7
      sulphobenzofurazan. Use as substrates for enzymes of the mercapturic acid
      xenobiotic pathway.
AB  - Fluorescent adducts of 4-chloro-7-sulphobenzofurazan with cysteine,
      cysteinylglycine, reduced glutathione and N-acetylcysteine were prepared. Adducts
      were separated by HPLC on a 3-mm Nova-Pak C18 reversed-phase column using
      isocratic elution with a solvent of acetonitrile-0.15 M phosphoric acid (5:95)
      buffered at pH 2.5. The adducts were detected using a fluorescence detector set
      at an excitation wavelength of 365 nm and an emission wavelength of 510 nm and an
      ultraviolet detector at 254 nm. The adduct of reduced glutathione was also formed
      by the action of the enzyme glutathione-S-transferase. This adduct acted as a
      substrate for the enzyme gamma-glutamyltranspeptidase and the product of this
      reaction, the 4-chloro-7-sulphobenzofurazanyl derivative of cysteinylglycine,
      acted as a substrate for either dipeptidase or aminopeptidase M. The sequential
      enzymic effects could be detected by changes in the relative fluorescence
      intensity of the solutions to which the respective enzymes had been added but
      were more appropriately followed by changes in the HPLC elution profiles after
      enzymic treatment of solutions.

PMID- 9653923
TI  - Analysis of urinary caffeine metabolites to assess biotransformation enzyme
      activities by reversed-phase high-performance liquid chromatography.
AB  - An isocratic high-performance liquid chromatography procedure was developed for
      the analysis of five urinary metabolites of caffeine; caffeine or 1,3,7
      trimethylxanthine (137X), paraxanthine or 1,7-dimethylxanthine (17X), 1,7
      dimethylurate (17U), 1-methylxanthine (1X), 1-methylurate (1U) and 5-acetylamino
      6-formylamino-3-methyluracil (AFMU). A standardized procedure was used for oral
      intake of caffeine and for urine collection. Conditions for sample storage and
      preparation were optimized, resulting in no detectable loss of caffeine
      metabolites after storage of the urine samples for four months. Urine samples
      were extracted with chloroform-2-propanol (4:1, v/v) and separated on a reversed
      phase column with acetic acid (33%)-tetrahydrofuran-acetonitrile-water
      (1:2.5:44:925.5, v/v) as the eluent. Peaks were monitored at 280 nm. Peak heights
      were measured and the five metabolites were quantified using calibration curves.
      Cytochrome P4501A2 (CYP1A2) activity was calculated from the molar ratio
      (AFMU+1X+1U)/17U, N-acetyltransferase (NAT) from the ratio AFMU/1X, XO from the
      ratio 1U/1X+1U and cytochrome P4502A6 (CYP2A6) from the ratio 17U/(17U+17X+1U+
      1X+AFMU). The inter-assay coefficients of variation ranged from 1.7% for 17U to
      5.7% for IX. The intra-individual variation in metabolite ratios determined in
      two people, with intervals of a few days to several weeks between measurements,
      ranged from 2. 1% for XO to 11.0% for CYP2A6. Using this procedure, metabolic
      ratios were determined for four groups of subjects; healthy, non-smoking females
      using oral contraceptives (OC users, n=5) and non-users (n=5), healthy nonsmoking
      males (n=9) and children (n=7). Results found in this study were comparable to
      results reported in the literature for subjects with similar characteristics. A
      significantly higher CYP1A2 ratio was found for males (4.87+/-0.47) compared to
      females (3.62+/-0.91: p=0.005, Mann-Whitney). For the other enzyme activities, no
      significant differences were found between the groups of subjects in this study.

PMID- 9653924
TI  - Simple microbore high-performance liquid chromatographic method for the
      determination of dopamine and cocaine from a single in vivo brain microdialysis
      sample.
AB  - A microbore chromatographic method for the analysis of both dopamine and cocaine
      from in vivo brain microdialysis samples is described. To eliminate the need for
      separate chromatographic systems for each analyte, post-column electrochemical
      and ultraviolet detection systems were arranged in series. The limit of
      quantitation for dopamine (5 fmol) was well within range for detecting dialysate
      concentrations of this neurotransmitter in rats which were in a baseline, drug
      free state. The limit of quantitation for cocaine (0.5 pmol) was sufficient to
      detect brain cocaine levels following the peripheral administration of a low dose
      of this psychostimulant (5 mg/kg, i.p.). Estimates of dialysate dopamine and
      cocaine concentrations after 5, 10 and 20 mg/kg cocaine (i.p.) were in agreement
      with reports which utilized separate HPLC analyses for each analyte.

PMID- 9653925
TI  - Quantification of busulfan in plasma by gas chromatography-mass spectrometry
      following derivatization with tetrafluorothiophenol.
AB  - A specific and highly sensitive method has been developed for the determination
      of busulfan in plasma by gas chromatography-mass spectrometry using a deuterium
      labeled busulfan (busulfan-d8) as internal standard. Plasma containing busulfan
      and busulfan-d8 were extracted with ethyl acetate and derivatized with 2,3,5,6
      tetrafluorothiophenol prior to the monitoring of specific ions. The limit of
      quantification of the assay was 20 ng/ml and the calibration curve was linear
      over the range of 10 to 2000 ng/ml of derivatized busulfan. This method was in
      good agreement with the GC-MS assay using derivatization with sodium iodide and
      measuring diiodobutane. In addition, a pharmacokinetic study of busulfan was
      conducted in six children. The apparent oral clearance was 5.7+/-1.9 ml/kg/min
      and the volume of distribution was 1.0+/-0.4 l/kg and were similar to those
      previously reported in pediatric patients.

PMID- 9653926
TI  - Determination of ropivacaine and [2H3]ropivacaine in biological samples by gas
      chromatography with nitrogen-phosphorus detection or mass spectrometry.
AB  - Bioanalytical methods for determining the total concentration of the new local
      anaesthetic drug ropivacaine in blood plasma, urine and tissues are presented.
      Ropivacaine is a drug mainly used in connection with surgery and for post
      operative pain relief. The biological samples were prepared using liquid-liquid
      extraction and analysed using capillary gas chromatography with nitrogen
      phosphorus detection or mass spectrometry. The methods are highly selective and
      reliable with a between-day precision, given as the relative standard deviation,
      generally below 6%. More than 20000 samples have been analysed using the methods
      described.

PMID- 9653927
TI  - Gas chromatographic-mass spectrometric quantitation of dextropropoxyphene and
      norpropoxyphene in hair and whole blood after automated on-line solid-phase
      extraction. Application in twelve fatalities.
AB  - After conversion of norpropoxyphene (NP) to its corresponding amide,
      dextropropoxyphene (DP) and NP are extracted from 1 ml of blood or 50 mg of
      powdered hair, on C18 cartridges and eluted using methanol containing 0.5% acetic
      acid. Automated extraction is conducted on-line with automated device, starting
      from buffered and centrifuged sample. After extraction, the dried residue is
      reconstituted with 40 microl of methanol, and then injected in a gas
      chromatograph at 250 degrees C. Quantitation is carried out by gas chromatography
      mass spectrometry in the selected-ion monitoring mode, lidocaine being the
      internal standard. The method gave relative standard deviations lower than 6.2%
      in whole blood, and 6.0% in hair for the entire range of calibration from 0.5 to
      10 microg/ml in blood and from 1 to 20 ng/mg in hair of both compounds. Limits of
      detection in blood and hair for DP are, respectively, 0.07 microg/ml and 0.05
      ng/mg, whereas the respective limits of detection in whole blood and hair for NP
      are 0.09 microg/ml and 0.04 ng/mg. The present method was used for one year in
      our laboratory. Postmortem concentrations of DP in blood ranged from 1.6 to 44.0
      microg/ml (mean=9.8microg/ml, n = 12) and are comparable to those found in the
      literature. Out of 30 hair samples from people who died from heroin overdose, 13
      were positive both for DP and NP with concentrations ranging from 0.2 to 27.4
      ng/mg (mean 8.7 ng/mg) for DP and 0.3 to 68.9 ng/mg (mean 24.1 ng/mg) for NP.

PMID- 9653928
TI  - Gas chromatographic-tandem mass spectrometric determination of acetylsalicylic
      acid in human plasma after oral administration of low-dose aspirin and guaimesal.
AB  - A fully validated gas chromatographic-tandem mass spectrometric (GC-MS-MS) method
      is described for the accurate determination of acetylsalicylic acid (ASA) in
      human plasma after a single low-dose oral administration of aspirin or guaimesal,
      an ASA releasing prodrug. ASA and the newly prepared O-[2H3]-acetylsalicylic acid
      (d3-ASA) used as internal standard were determined in 100-microl aliquots of
      plasma by extractive pentafluorobenzyl (PFB) esterification using PFB bromide and
      tetrabutylammoniumhydrogen sulphate as the esterifying and ion-pairing agent,
      respectively, and by GC-MS-MS analysis in the negative-ion chemical ionization
      mode. The overall relative standard deviations were below 8% for ASA levels in
      the range 0-1 microg/ml plasma. Mean accuracy was 3.8% for ASA levels within the
      range 0-100 ng/ml. The limit of quantitation of the method was determined as 200
      pg/ml ASA at an accuracy of 5.5% and a precision of 15.2%. The limit of detection
      was determined as 546 amol of ASA at a signal-to-noise ratio of 10:1.

PMID- 9653929
TI  - High-performance liquid chromatographic determination of drugs and metabolites in
      human serum and urine using direct injection and a unique molecular sieve.
AB  - Silicalite is a molecular sieve that contains an intricate system of channels
      approximately 6 A in diameter. These channels are hydrophobic and have been shown
      to retain relatively small hydrophobic and hydrophilic molecules from aqueous and
      biological samples. Silicalite is shown to be a restricted-access medium that
      permits the injection of biological fluids directly onto a HPLC column packed
      with Silicalite, eliminating the need for sample preparation. The sample
      macromolecules elute with high recovery mostly at the extraparticulate void.
      Simultaneously, Silicalite allows various drugs and metabolites to enter the
      channels and be retained. Recoveries >90% were generally obtained for a wide
      variety of drugs and their metabolites from human serum and urine.

PMID- 9653930
TI  - Determination of quinolone antibiotics in growth media by reversed-phase high
      performance liquid chromatography.
AB  - A simple, accurate, precise, and versatile high-performance liquid
      chromatographic (HPLC) method was developed and validated for the determination
      of three quinolone antibodies in Mueller-Hinton broth. The fluoroquinolone agents
      studied were ciprofloxacin, ofloxacin, and sparfloxacin; other quinolone agents
      have been identified using this method but not validated in this matrix
      (levofloxacin, clinafloxacin, temafloxacin, and trovafloxacin). In addition,
      several other biological growth mediums have been investigated (human serum,
      human urine, Todd-Hewitt growth media, Ensure enteral feeding solution, and
      Haemophilus growth media). This method uses UV detection (280 nm), a simple, one
      step protein precipitation extraction, and separation using a C18 column with an
      isocratic, ion-pairing mobile phase. An appropriate internal standard was
      obtained by using another quinolone antibiotic of differing retention time. The
      calibration curves were linear (r2> or =0.999) over a concentration range of
      0.0625-20.0 microg/ml with a lower limit of quantification of 0.1 microg/ml. The
      intra-day and inter-day coefficients of variation were less than 15%.

PMID- 9653931
TI  - Stereoselective determination of R,S-2-[4-(3-methyl-2-thienyl)phenyl]propionic
      acid and its taurine conjugates in dog urine by high-performance liquid
      chromatography.
AB  - Two high-performance liquid chromatographic methods for the stereoselective
      determination of R,S-2-[4-(3-methyl-2-thienyl)-phenyl]propionic acid (R,S-MTPPA),
      a new anti-inflammatory agent, and its taurine conjugates (R,S-MTPPA-TAU) in dog
      urine have been developed and validated. The urine samples were subjected to
      solid extraction or TLC preparation, then R,S-MTPPA and R,S-MTPPA-TAU were
      separated on Chiralcel OD and Chiral AGP columns, respectively, with ultraviolet
      absorbance detection at 272 nm. The dose-response relationships for enantiomers
      of R,S-MTPPA and R,S-MTPPA-TAU were linear in the concentration ranges of 0.5-50
      (r>0.9993) and 5-200 microg/ml (r>0.9982), respectively. Recoveries of all tested
      enantiomers from dog urine were roughly 90% within the above concentration
      ranges. Intra- and inter-day reproducibilities were sufficient for metabolic
      studies. These methods were applied to stereoselective determination of the
      enantiomers in dog urine after administration of either S- or R-MTPPA.

PMID- 9653932
TI  - High-performance liquid chromatographic assay for the novel antitumor drug,
      bryostatin-1, incorporating a serum extraction technique.
AB  - An HPLC assay incorporating a solid-phase extraction technique has been devised
      for bryostatin-1. Quantitation of bryostatin was found to be linear over the
      concentration range 0.012-25 microg/ml (0.2-25 ng on column) and was found to
      have a limit of detection of 0.2 ng on column, with a correlation coefficient of
      0.9999. Following extraction of bryostatin over a range of concentrations from
      horse serum (0.012-25 microg/ml) and human serum (0.01-0.32 microg/ml) using a
      100-mg C18 solid-phase extraction cartridge, extraction efficiencies consistently
      greater than 90% were obtained for extraction from horse serum and varied between
      57 and 85% from human serum. However, on extending this work to blood samples
      from patients undergoing therapy with bryostatin-1, the drug was not detectable
      even at the maximum dose given, demonstrating the rapid loss of this agent from
      peripheral circulation.

PMID- 9653933
TI  - New isocratic high-performance liquid chromatographic procedure to assay the anti
      sickling compound hydroxyurea in plasma with ultraviolet detection.
AB  - A new procedure using high-performance liquid chromatography (HPLC) with
      ultraviolet detection to assay hydroxyurea (HU) levels in plasma has been
      developed. The drug was isolated from plasma by a direct deproteinization process
      with sulfosalicylic acid. Following neutralization of the acidic supernatant, an
      aliquot was loaded onto an Aminex HPX-72S column (300x7.8 mm). Chromatography was
      performed at 55 degrees C using a mobile phase consisting of acetonitrile-0.025 M
      ammonium sulfate buffer (pH 8.5) including 0.1% triethylamine, 0.01 M sodium
      sulfate, and 5 mM sodium heptane sulfonate. The UV absorbance of effluent was
      monitored at 214 nm. A flow-rate of 0.8 ml/min was used for analyzing HU in both
      human and mouse plasma. Under these conditions, the drug eluted at 12.6 min. The
      assay possessed linearity up to 425 microg/ml, with a lower limit of quantitation
      of 3.32+/-0.0004 microg/ml (mean+/-S.D., n=10). Intra-day and inter-day
      coefficients of variation were less than 8.5% and 8.7% respectively. Absolute
      differences were less than 7.4%. The method has been employed in clinical studies
      and the sensitivity of the assay was shown to be adequate for characterizing the
      plasma pharmacokinetics of HU in mice. In conclusion, the procedure described
      herein could be ideally suited for therapeutic monitoring of hydroxyurea.

PMID- 9653934
TI  - Determination of minalrestat (an aldose reductase inhibitor) in rat, dog and
      human plasma by high-performance liquid chromatography.
AB  - A high-performance liquid chromatographic (HPLC) method was developed for the
      quantification of minalrestat (a potent aldose reductase inhibitor) in rat, dog
      and human plasma. Minalrestat and internal standard (I.S.) were extracted from
      plasma by either solid-phase extraction (SPE) or liquid-liquid extraction (human
      plasma). Plasma extracts were chromatographed on a Hypersil ODS column with 3
      microm packing with a mobile phase of acetonitrile-0.05 M potassium phosphate
      buffer, pH 3.0 (45:55, v/v) at 0.2 ml/min. The signal in the eluent was enhanced
      by UV-irradiation when passing through a photochemical reaction unit with a 10-m
      reaction coil, prior to detection by UV absorbance at 255 nm. The intra-day
      coefficients of variation was less than 9% in rat, dog and human plasma and the
      intra-day accuracy (%MRE) was within +/-5% in all matrices tested. The inter-day
      coefficients of variation were less than 12% in rat and human plasma and the
      accuracy (%MRE) was within +/-15%. Minalrestat was stable for at least 60 days in
      rat and human plasma and at least 30 days in dog plasma samples stored at -20
      degrees C. In human plasma samples, the analyte was stable for up to 5 cycles of
      freezing and thawing. This method has been applied successfully for the
      evaluation of the pharmacokinetics of minalrestat in rats, dogs and humans.

PMID- 9653935
TI  - Determination of trichlormethiazide in bovine milk by high-performance liquid
      chromatography.
AB  - A liquid chromatographic procedure was developed and validated for the
      quantitative determination of trichlormethiazide (TCMTZ) in bovine milk. Whole
      milk was defatted by initial centrifugation at 4 degrees C. The resulting skim
      milk was treated with lead acetate and acetonitrile, vortex mixed, and
      centrifuged. The acetonitrile from the supernatant was back extracted in ethyl
      acetate. The organic solvent mixture which contained TCMTZ was further treated
      with sodium tungstate, vortex mixed, and centrifuged. The top organic layer was
      removed and evaporated to dryness; the resulting residue was reconstituted in the
      mobile phase, and the final extract was analyzed by high-performance liquid
      chromatography (HPLC). The HPLC conditions employed included a polymer column, a
      mobile phase consisting of 30% acetonitrile or 30% acetonitrile-tetrahydrofuran
      (2:1, v/v) in a phosphate buffer (pH 3), and a UV detection at 225 nm. The
      average recoveries of TCMTZ from milk fortified at 7, 14, 35, 70, and 140 ppb
      were 88, 93, 117, 110, and 99%, respectively, with corresponding C.V. values of
      7, 18, 11, 9, and 21%. The method was validated by assaying milk obtained from a
      cow dosed with Naquasone. TCMTZ concentration was detected only in the 8 h post
      dose milk samples and was determined to be 6 ppb.

PMID- 9653936
TI  - Application of matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry to the analysis of glycopeptide-containing multiple O-linked
      oligosaccharides.
AB  - In our previous report [Iwase et al., J. Biochem., 120 (1996) 393], the number of
      O-linked oligosaccharide chains on the hinge region of IgA1 was estimated by
      matrix-assisted laser desorption ionization time-of-flight mass spectrometry
      (MALDI-TOFMS). In this experiment, the number of non-substituted N
      acetylgalactosamines and Galbeta1,3GalNAc residues, as the core O-linked
      oligosaccharide structure per heavy chain of normal human serum IgA1, was
      estimated by digestion of the asialo-hinge glycopeptide with alpha-N
      acetylgalactosaminidase (GalNAc-ase) or endo-alpha-N-acetylgalactosaminidase
      (endo-GalNAc-ase). GalNAc-ase treatment of the asialoglycopeptide produced two
      major peaks, one being a glycopeptide containing four GalNAc and four Gal
      residues, and the other contained three GalNAc and three Gal residues. Treatment
      with endo-GalNAc-ase also produced a nearly equal amount of the two peaks, with
      the naked hinge peptide and the peptide having one GalNAc residue. From those
      results, we concluded that the asialo-hinge glycopeptide was composed of three
      components bearing four Galbeta1,3GalNAc and one GalNAc, only four
      Galbeta1,3GalNAc, and three Galbeta1,3GalNAc and one GalNAc, respectively. This
      method was useful for determining the glycoforms on the IgA1 molecule with
      respect to the core O-linked oligosaccharide structure.

PMID- 9653937
TI  - Quantification of carbamylated dehydroascorbate derivative produced from cyanate
      and dehydroascorbate.
AB  - We established a high-performance liquid chromatographic method for separating
      and quantifying carbamylated dehydroascorbate derivative (CDA), a reaction
      product of cyanate with dehydroascorbate. The separation of CDA from interfering
      substances was achieved by anion-exchange HPLC using a TSK gel SAX (250x4.6 mm
      I.D.) column and 0.12 M NaCl eluent. The detection of CDA was achieved through
      two steps: (1) degradation of CDA to cyanate and amino compounds in alkaline
      solution, and (2) detection of these products by an indophenol reaction. For the
      processing of plasma and urine samples, anion-exchange solid-phase extraction was
      used. The detection limit for quantitative determination was 0.1 microM CDA
      (S/N=3). The linear range found applying the optimized conditions was 0.2 to 200
      microM. The intra- and inter-day assay precision (R.S.D.) of CDA (10 microM) were
      4.8 and 7.2% for rat plasma, and 4.0 and 4.9% for rat urine, respectively. The
      usefulness of the present method was proved by the application to plasma and
      urine samples. The study of the biokinetics of CDA in rats revealed that the
      elimination of CDA is due to urinary excretion.

PMID- 9653938
TI  - Direct pharmaceutical analysis of bisphosphonates by capillary electrophoresis.
AB  - Bisphosphonate compounds have been studied as a class of potential drugs for the
      treatment of various bone diseases. However, the analyses of these compounds are
      problematic because most of them do not contain strong chromophores. Based on the
      unique structures of these compounds, we have employed a capillary
      electrophoresis (CE) technique for the characterization of these compounds in
      pharmaceutical dosage formulations. In this study, two CE methods were developed
      for the determination of a bisphosphonate compound, 2-thioethane-1,1
      bisphosphonic acid. The first method involved the use of an uncoated column, a
      phosphate buffer, and hydrostatic injection with direct UV absorbance detection.
      The method showed excellent resolution and precision with a reasonable detection
      limit of 30 microg/ml. Sensitivity was further improved using a glycerol-coated
      column, together with a phosphate buffer of higher concentration and
      electrokinetic injection under sample stacking conditions. This modified method
      revealed a significant improvement in sensitivity with a detection limit of about
      50 ng/ml. Both methods demonstrated high simplicity and excellent reproducibility
      and were successfully applied to the quantitative analyses of pharmaceutical
      dosing solutions.

PMID- 9653939
TI  - Influence of Cremophor EL on the quantification of paclitaxel in plasma using
      high-performance liquid chromatography with solid-phase extraction as sample
      pretreatment.
AB  - For the quantitative determination of paclitaxel in human plasma reversed-phase
      high-performance liquid chromatographic (HPLC) methods with solid-phase
      extraction (SPE) as sample pretreatment procedure are frequently used. Recovery
      problems arose during the quantification of paclitaxel in plasma samples of
      patients. The major problems were a large batch-to-batch difference in
      performance of the SPE columns and the effects of the pharmaceutical vehicle
      Cremophor EL on the performance of the SPE. Cremophor EL concentrations exceeding
      1.0% (v/v) had a great impact on the absolute recovery of paclitaxel from human
      plasma with the SPE procedure. The recoveries decreased approximately 10 to 40%
      depending on the quality of the batch SPE columns. The problems are avoided by
      using 2'-methylpaclitaxel as the internal standard. This study points out the
      importance of including the effects of a pharmaceutical vehicle, like Cremophor
      EL, in the validation programme of a bioanalytical assay and the use of an
      internal standard in HPLC paclitaxel assays preceded by SPE as sample
      pretreatment procedure.

PMID- 9653940
TI  - Ion chromatography method and validation for the determination of sulfate and
      sulfamate ions in topiramate drug substance and finished product.
AB  - A stability-indicating assay method has been developed for monitoring topiramate
      degradation in drug substance and finished product by quantifying sulfamate and
      sulfate ions. Topiramate in the solid state is stable under ambient conditions
      but can degrade under stress conditions (elevated temperatures and humidities).
      This method detects and quantitates sulfamate and sulfate ions (the inorganic
      part of the decomposition) and in conjunction with an assay method for topiramate
      and its known organic degradation product provides total molar accountability.
      The chromatographic system consists of a sodium hydroxide gradient (2-25 mM) and
      an anion-exchange HPLC column and an anion suppressor. The analysis is complete
      in 30 min. The method utilizes the same sample preparation as the topiramate
      assay method which increases sample efficiency and throughput. The method has
      been validated for analysis of degraded and nondegraded topiramate drug substance
      and finished product.

PMID- 9653941
TI  - Modified cyclodextrins as chiral selectors: molecular modelling investigations on
      the enantioselective binding properties of heptakis(2,3-di-O-methyl-6-O-tert.
      butyldimethylsilyl)-beta-cyclodextri n.
AB  - Molecular modelling methods have been used to investigate the enantioselective
      binding properties of chiral dihydrofuranones on heptakis(2,3-di-O-methyl-6-O
      tert.-butyldimethylsilyl)-beta-cyclod extrin in capillary gas chromatography. A
      conformational analysis of the modified beta-cyclodextrin was performed using
      annealed molecular dynamics. With the program GRID the molecular interaction
      potential for each of the received energetically reasonable structures of the
      beta-cyclodextrin and the dihydrofuranones was evaluated using different probe
      groups. The results of these computations have been used as starting points for
      constructing geometrically reasonable host-guest complexes between the beta
      cyclodextrin and the dihydrofuranones. The subsequently performed molecular
      dynamics simulations yielded different complex states reflecting the
      conformational flexibility of the diastereomeric complexes. Considering the
      evaluated interaction energy between the beta-cyclodextrin and the
      dihydrofuranones as a measure of complex stability the results are in close
      agreement with the experimentally determined elution sequences. The methodology
      for the construction of the interaction model used in this study is capable of
      simulating the experimental data. We believe that it may serve as a basis for
      predictions of hitherto unknown elution sequences at modified cyclodextrins.

PMID- 9653942
TI  - Rapid separation and quantitation of combined neutral and polar lipid classes by
      high-performance liquid chromatography and evaporative light-scattering mass
      detection.
AB  - Modifications are described for an innovative and widely used high-performance
      liquid chromatography technique that resolves a very broad spectrum of lipids for
      quantitation by evaporative light-scattering detection. Substitution of acetone
      for 2-propanol in a portion of the solvent gradient program yields consistent
      resolution of diacylglycerol and cholesterol without sacrificing baseline
      resolution of the remaining major lipid classes. Moreover, previously noted
      instabilities in triacylglycerol retention time are eliminated. The introduction
      of acetone also enables a 20% reduction in flow-rate without an increase in total
      run time. As a further modification of the mobile phase composition, acetic acid
      and ethanolamine are substituted for the serine-ethylamine combination that was
      originally shown to improve column performance. The combination of acetic acid
      and ethanolamine yields the same result but the increased volatility of these
      solutes over serine results in decreased baseline noise. Finally, 1,2
      hexadecanediol is introduced as an internal standard that is well suited for this
      method. The chromatographic performance obtained with these modifications is
      demonstrated in compositional analyses of lipid extracts from rat liver, heart,
      kidney and brain.

PMID- 9653943
TI  - Determination of glutamate and aspartate in microdialysis samples by reversed
      phase column liquid chromatography with fluorescence and electrochemical
      detection.
AB  - Five different systems for fast determination of aspartate and glutamate in
      microdialysis samples are described: (I) a high-speed HPLC using a gradient pump
      with a sharp elution profile, (II) a column switching technique, (III) an
      isocratic pump with a low-pressure switching valve for one-step gradients, (IV)
      microbore chromatography using injections of acetonitrile as a wash-out step, (V)
      on-line connection of microdialysis and HPLC/derivatization. In all cases,
      automated precolumn derivatization with o-phthalaldehyde-2-mercaptoethanol
      reagent were used. Both fluorescence and electrochemical detection techniques
      were evaluated in terms of reproducibility, sensitivity, interference,
      maintenance and troubleshooting. The electrochemical detection method required a
      second derivatization step with 0.2 M iodoacetamide to remove excess of a thiol
      moiety and regular recalibrations after each six to ten injections. Under these
      conditions the correlation coefficients for electrochemical vs. fluorescence
      detectors were 0.918 for Asp and 0.988 for Glu for 65 microdialysis samples.
      Coefficients of variation for six analyses between calibrations were below 3% for
      both detectors. The limits of detection for both amino acids were about 0.4 pmol
      for electrochemical detection with a thiol scavenger step, 50 fmol for
      fluorescence detection using conventional columns and about 20-30 fmol for the
      microbore system. All systems are suitable for detecting basal levels of Asp and
      Glu in 5-10 microl microdialysis samples from a rat brain where typical
      concentrations lie around 1-10 pmol or more. It is concluded that a microbore
      setup with one isocratic pump and an autosampler optimized for injections of
      washing solvent between samples is the most practical and economical. The system
      allows analysis of minute sample volumes down to 1-2 microl.

PMID- 9653944
TI  - Highly sensitive measurement of lipid molecular species from biological samples
      by fluorimetric detection coupled to high-performance liquid chromatography.
AB  - As the molecular species composition of glycerophospholipids provides more
      valuable information than the corresponding fatty acid composition, we have
      applied a fluorimetric detection (360 and 460 nm for excitation and emission
      wavelengths, respectively) of anthroyl derivatives of diradylglycerol species to
      minor phospholipid classes and subclasses from biological samples. Diacylglycerol
      species were obtained by phospholipase C treatment of phosphatidylcholine
      subclasses and phosphatidic acid extracted from rat thymocytes. Subpicomole
      measurements of molecular species from the minor subclass
      alkenylacylglycerophosphocholine could be achieved (e.g. 0.4 pmol of the
      18:1/20:5 species). Such a sensitivity allowed study of the molecular species
      composition of another minor phospholipid, phosphatidic acid, and to evaluation
      of its alteration in mitogen-stimulated thymocytes as compared to unstimulated
      ones. Finally, we report that such a measurement is also applicable to other
      minor bioactive lipids with a hydroxyl group available, namely
      hydroxyeicosatetraenoates (HETEs), with a similar gain of sensitivity over
      conventional UV detection. Overall, these measurements, especially those of
      phospholipid molecular species, are sensitive, reliable and meaningful for
      precursor-product relationship between phospholipids.

PMID- 9653945
TI  - Determination of gamma-aminobutyric acid in microdialysis samples by microbore
      column liquid chromatography and fluorescence detection.
AB  - A method for the determination of gamma-aminobutyric acid (GABA) at
      concentrations as low as 1.5 nM in microdialysis samples is described. A high
      performance liquid chromatography (HPLC) autosampler was used for precolumn
      derivatizations of samples with phthalaldehyde-2-mercaptoethanol reagent, as well
      as for automated injections of acetonitrile to wash the microbore column between
      injections. This permitted the use of only one isocratic pump and reduced the run
      to-run analysis time to below 20 min, without any risk for late-eluting peaks.
      Three different microbore columns were evaluated. The optimal column was a 150 x
      1 mm I.D., C18 reversed-phase silica column with a particle size of 3 microm,
      operated at a flow-rate of 50 microl/min. The mobile phase was 0.1 M sodium
      acetate buffer, pH 5.4, containing 20% acetonitrile. Under these conditions, the
      column exhibits a low back-pressure of about 11.1 MPa and is usable for at least
      1000 injections. Good correlation was found between fluorescence and
      electrochemical detector responses for o-phthaldialdehyde-GABA derivatives,
      although the latter detector type generally required more skill and maintenance
      for routine use. Microdialysis samples of 10-20 microl, recovered from various
      rat brain nuclei, were assayed using the described method.

PMID- 9653946
TI  - Analysis of cysteine and N-acetylcysteine in human plasma by high-performance
      liquid chromatography at the basal state and after oral administration of N
      acetylcysteine.
AB  - A high-performance liquid chromatographic method for the determination of free
      reduced cysteine and N-acetylcysteine in human plasma at the basal state and
      after oral administration of N-acetylcysteine is described. The method is based
      on acid-catalysed conversion of plasma thiols to the corresponding S-nitroso
      derivatives by excess of nitrite and their subsequent cation-pairing RP-HPLC with
      detection at 333 nm. Recovery rates of cysteine and N-acetylcysteine added to
      human plasma were 94.6 and 99.6%, respectively. Inter- and intra-day precision
      were below 6%. In healthy humans (n = 5), free reduced cysteine was determined to
      be (mean+/-S.E.) 10.0+/-0.96 microM. No N-acetylcysteine was detected in plasma
      of these subjects above the limit of detection (e.g. 170 nM). The method was
      successfully applied to a pharmacokinetic study on orally administered N
      acetylcysteine to healthy volunteers.

PMID- 9653947
TI  - Sensitive method for the quantification of beta-glucuronidase activity in human
      urine using capillary electrophoresis with fluorescence detection.
AB  - Capillary electrophoresis (CE) with fluorescence detection was used to determine
      the concentration of 4-methylumbelliferone liberated from 4-methylumbelliferyl
      beta-D-glucuronide by beta-glucuronidase. Enzyme substrate saturation kinetics
      were studied in buffer and the pH range for the enzyme reaction was optimized. A
      linear relationship of initial enzyme reaction velocity as a function of peak
      area of enzyme product was obtained for enzyme activity ranging from 1 to 100
      units. The beta-glucuronidase activity in urine was next determined. Freshly
      collected urine samples were dialyzed, the retentate was incubated with 4
      methylumbelliferyl-beta-D-glucuronide, boiled and centrifuged. The supernatant
      was separated by CE in an uncoated capillary with 0.1 M sodium acetate buffer by
      applying a voltage of 12 kV. The product of the enzymatic reaction, 4
      methylumbelliferone, was detected by fluorescence, facilitating the determination
      of as little as one unit of beta-glucuronidase activity in a 0.5-h incubation
      time, with an error of less than +/-5%.

PMID- 9653948
TI  - Determination of lycopene, alpha-carotene and beta-carotene in serum by liquid
      chromatography-atmospheric pressure chemical ionization mass spectrometry with
      selected-ion monitoring.
AB  - A selected-ion monitoring (SIM) determination of serum lycopene, alpha-carotene
      and beta-carotene by an atmospheric pressure chemical ionization mass
      spectrometry (APCI-MS) was developed. A large amount of serum cholesterols
      disturbed the SIM determination of carotenoids by contaminating the segment of
      interface with the LC-MS. Therefore, separation of carotenoids from the
      cholesterols was performed using a mixed solution of methanol and acetonitrile
      (70:30) as the mobile phase on a C18 column of mightsil ODS-5 (75 mm x 4.6 mm
      I.D.). The SIM determination was carried out by introducing only the peak
      portions of carotenoids and I.S. (squalene) by means of an auto switching valve.
      In the positive mode of APCI-MS, lycopene, alpha-carotene and beta-carotene were
      monitored at m/z 537 and I.S. was monitored at m/z 411. This method was linear
      for all analytes in the range of 15-150 ng for lycopene, 7-70 ng for alpha
      carotene and 25-50 ng for beta-carotene. The detection limit of LC-APCI-MS-SIM
      for carotenoids was about 3 ng per 1 ml of serum (S/N = 3). The repeatabilities,
      expressed as C.V.s, were 10%, 8.4% and 5.3% for lycopene, alpha-carotene and beta
      carotene, respectively. The intermediate precisions, expressed as C.V.s, were
      11.2%, 8.8% and 6.5% for lycopene, alpha-carotene and beta-carotene,
      respectively.

PMID- 9653949
TI  - Subnanomolar quantification of caffeine's in vitro metabolites by stable isotope
      dilution gas chromatography-mass spectrometry.
AB  - A method for the quantification of subnanomolar levels of in vitro metabolites of
      caffeine by an isotope dilution gas chromatographic-mass spectrometric (GC-MS)
      assay has been developed and applied. Trideuteromethylated analogs of each
      primary metabolite were synthesized and added after incubations of caffeine with
      human liver microsomes high in cytochrome P4501A2. HPLC separation of the
      metabolites prior to GC-MS quantification allowed the isolation of theobromine
      and paraxanthine which coeluted by GC and enabled quantification over a larger
      dynamic range. Quantitative analysis was performed on the n-propylated
      derivatives by selected-ion monitoring of either the M+. ions for the
      dimethylxanthines or [M-C3H6]+. ions for 1,3,7-trimethyluric acid. For the least
      abundant metabolite (1,3,7-trimethyluric acid), the detection level on column was
      200 pg. Replicate analyses exhibited intra- and inter-day variability of 4.2 and
      7.9%, respectively. This assay has been successfully used in the quantification
      of caffeine's primary metabolites in more than 180 incubations, at varying
      substrate concentrations and with multiple enzyme sources.

PMID- 9653950
TI  - Rapid method for the simultaneous measurement of nicotine and cotinine in urine
      and serum by gas chromatography-mass spectrometry.
AB  - A simple, sensitive, and rapid gas chromatographic-mass spectrometric method is
      described for the simultaneous detection and quantitation of nicotine and its
      metabolite, cotinine, in urine and serum. The analytes and their respective
      deuterated internal standards were extracted by liquid-liquid extraction coupled
      to centrifugation and evaporation. The detection limit of the assay was 0.16
      ng/ml for both nicotine and cotinine. The limit of quantitation for each analyte
      was 1.25 ng/ml.

PMID- 9653951
TI  - Rapid and sensitive high-performance liquid chromatographic determination of
      nicotine and cotinine in nonsmoker human and rat urines.
AB  - A simple reversed-phase high-performance liquid chromatographic method with
      paired-ion and UV detection has been developed for the rapid quantification of
      urinary nicotine and cotinine. A one-step solid-liquid extraction on Extrelut was
      used. Separation from endogenous substances was achieved with a decreasing flow
      rate. With 20 ml of urine for extraction, the limit of quantification was 0.5
      ng/ml for cotinine and 5 ng/ml for nicotine; linearity was obtained from 50 to
      5000 ng/ml. The intra- and inter-day coefficients of variation were less than 9%
      for cotinine and 30% for nicotine. Average recoveries for cotinine were 92-100%
      and 47-86% for nicotine. The present method was applied to the urine analysis of
      smokers, nonsmoker children, and experimental animals.

PMID- 9653952
TI  - Determination of pilocarpine, isopilocarpine, pilocarpic acid and isopilocarpic
      acid in human plasma and urine by high-performance liquid chromatography with
      tandem mass spectrometric detection.
AB  - A method is described for the determination of pilocarpine and its degradation
      products isopilocarpine, pilocarpic acid and isopilocarpic acid in human plasma
      and urine. The method is based on a simple sample preparation step --
      ultrafiltration for plasma and dilution for urine samples -- followed by a
      reversed-phase liquid chromatographic separation of the analytes and detection by
      means of tandem mass spectrometry. Parameters affecting the performance of these
      steps are discussed. The high sensitivity and selectivity of the method allow low
      ng/ml concentrations to be determined for all compounds in plasma and undiluted
      urine, which enables the investigation of the metabolic fate and elimination of
      pilocarpine after oral administration to humans.

PMID- 9653953
TI  - Validated method for the determination of idazoxan in human plasma by liquid
      chromatography with tandem mass spectrometric detection.
AB  - A liquid chromatography-tandem mass spectrometry method for the determination of
      idazoxan in human (heparin) plasma is presented, which was developed and
      validated using 500 microl of sample. Sample preparation consisted of the
      addition of fluoroidazoxan as the internal standard, extraction at alkaline
      conditions into tert.-butyl methyl ether, followed by centrifugation, evaporation
      of the solvent and reconstitution in methanol. After a short chromatographic run,
      detection took place by ionspray tandem mass spectrometry in positive ion mode.
      Validation results on linearity, specificity, accuracy, precision and stability,
      as well as application of the method to samples from a clinical trial, are shown.
      The validated calibration range is from 0.300 to 100 ng/ml, with accuracy (bias)
      and precision (coefficient of variation) being below 15% at all levels. A sample
      throughput of, typically, 150 per day can be achieved.

PMID- 9653954
TI  - Quantitative liquid chromatographic-tandem mass spectrometric determination of
      orlistat in plasma with a quadrupole ion trap.
AB  - This report evaluates the use of a quadrupolar ion trap for quantitation in a
      bioanalytical laboratory. The evaluation was accomplished with the cross
      validation of an LC-MS-MS quantitative method previously validated on a triple
      quadrupole mass spectrometer. The method was a multi-level determination of the
      anti-obesity drug, orlistat, in human plasma. The method has been refined
      previously on a triple quadrupole instrument to provide rapid sample throughput
      with robust reproducibility at sub-nanogram detection limits. Optimization of the
      method on the ion trap required improved chromatographic separation of orlistat
      from interfering plasma matrix components coextracted during the initial liquid
      liquid extraction of plasma samples. The ion trap produces full-scan collision
      induced dissociation mass spectra containing characteristic orlistat fragment
      ions that are useful for quantitation. Data collection on the ion trap required a
      precursor ion isolation width of 3.0 Da and optimal quantitative results were
      obtained when three fragment ions were monitored with a 1.8 Da window for each
      ion. Although a direct cross-validation between the ion trap and the tandem
      triple quadrupole mass spectrometer was not possible, quantitative results for
      orlistat comparable to those obtained from the triple quadrupole instrument were
      achieved by the ion trap with the modified method. The limit of quantitation for
      orlistat in plasma on the ion trap was 0.3 ng ml(-1) with a linear dynamic range
      of 0.3 to 10 ng ml(-1). Precision and accuracy varied from 4 to 15% over the
      quantitation range. The overall results provide an example of the utility of an
      ion trap in bioanalytical work.

PMID- 9653955
TI  - How to better define the characteristics of dispersion of results in liquid
      chromatographic analyses through an interlaboratory study. Example of
      collaborative studies on ketoprofen and spiramycin.
AB  - The aim of this study was to use statistical tools, especially the analysis of
      variance (ANOVA), to improve knowledge of the characteristics of the dispersion
      of results in high-performance liquid chromatography (HPLC) methods for
      quantitative analysis. It is in this regard that two interlaboratory studies have
      been carried out in collaboration with Rhone-Poulenc Rorer. The first concerned
      the analysis of a single drug product (ketoprofen) and was typically a "simple
      analysis". The second one involved a complex mixture of drug products and related
      substances (spiramycin), requiring far more constraining analysis conditions.
      Preliminary studies of the analyses were carried out to develop an optimized
      protocol. Statistical exploitation of the data for ketoprofen showed that there
      was no significant influence of the factors "laboratory" and "preparation", under
      the conditions of the study. On the other hand, in the case of spiramycin, a
      significant influence of the factors "laboratory" and "preparation" was observed
      under the conditions of the collaborative study, indicating that the latter
      factor must be taken into account to establish certified assays. Results of these
      two studies will help to determine the factors that have a significant influence,
      depending on the product and the chromatographic method used. By completing the
      statistical data base, interlaboratory studies will also contribute in the near
      future to the elaboration of more rigorous protocols for analytical transfers.

PMID- 9653956
TI  - Liquid chromatographic separation of doxycycline and 4-epidoxycycline in a tissue
      depletion study of doxycycline in turkeys.
AB  - Liver and muscle tissue residues of doxycycline in turkeys were determined
      following administration of 25 mg doxycycline x HCl/kg BW in the drinking water
      under field conditions. Quantitation was performed using a validated HPLC method
      with fluorescence detection. The method was able to separate doxycycline and its
      4-epimer, 4-epidoxycycline. This epimer was found in both liver and muscle
      tissue. The detection limits of the method were estimated at 1.2 ng/g and 1.0
      ng/g of doxycycline in liver and muscle tissue, respectively, using a signal-to
      noise ratio of 3:1. The recovery of doxycycline was determined from spiked
      tissues and was 63+/-3.8% and 66+/-3.1% for liver and muscle, respectively (n =
      6). Within-day and between-day imprecision, expressed as the R.S.D. was below
      7.4%. Linear calibration curves (r>0.997) were obtained in spiked liver between 0
      and 1500 ng/g and in spiked muscle between 0 and 500 ng/g. A good stability of
      doxycycline was observed in liver samples after storage for 22 days at -20
      degrees C. The correlation between the residues in the liver and the muscle was
      expressed as the correlation coefficient r and was 0.9884. The depletion kinetics
      of doxycycline fitted a one-compartment model. The elimination half-life (T1/2)
      of doxycycline was 77.7 h and 78.0 h in muscle and liver, respectively.
      Furthermore, the residue depletion kinetics were used to establish a withdrawal
      period in conformity with official guidelines. The withdrawal times necessary to
      reach concentrations below maximum residue limits (MRLs), as imposed by the EU,
      were 12 days and 17 days for liver and muscle tissue, respectively.

PMID- 9653957
TI  - Stability-indicating analysis of isoxazolyl penicillins using dual wavelength
      high-performance liquid chromatography.
AB  - Stability-indicating high-performance liquid chromatography analytical procedures
      were developed for specific determination of four isoxazolyl penicillins during
      degradation under neutral and accelerated acid/alkali conditions. The
      chromatographic conditions were set so that the drug peak was well separated from
      the peaks of the degradation products. Peak homogeneity of the resolving drug
      peak was assessed by the shape of the ratio chromatogram. Good and reproducible
      separations were achieved on a reversed-phase column using a mobile phase
      consisting of acetonitrile and a solution of 20 mM potassium dihydrogen phosphate
      plus 10 mM tetramethylammonium chloride in water (adjusted to pH 5). Optimal
      separations for all four drugs were achieved within the range of 15-21% organic
      modifier in the mobile phase. The detection wavelengths were 220 nm and 240 nm.
      The stability-indicating nature of the methods was confirmed by the linearity of
      the pseudo-first order plots. The utility of dual-wavelength chromatography in
      establishment of stability-indicating assays is highlighted.

PMID- 9653958
TI  - Simultaneous high-performance liquid chromatographic determination of
      quinupristin, dalfopristin and their main metabolites in human plasma.
AB  - Quinupristin-dalfopristin (30:70, w/w) is a new streptogramin, which has been
      developed for intravenous use. A specific and sensitive HPLC method was developed
      to measure simultaneously quinupristin (RP 57669) and dalfopristin (RP 54476) and
      their main metabolites in human plasma. The metabolites measured by this method
      were RP 69012 (glutathione-conjugated) and RPR 100391 (cysteine-conjugated) from
      quinupristin and RP 12536 (natural pristinamycin IIA), from dalfopristin. Solid
      phase extraction with disposable cartridges was combined with reversed-phase HPLC
      and fluorimetric detection for RP 57669, RP 69012 and RPR 100391 and UV detection
      for RP 54476 and RP 12536. The method provided good recovery and low limits of
      quantitation (0.025 mg l(-1) for RP 57669, RP 54476 and RP 12536, and of 0.010 mg
      l(-1) for RP 69012 and RPR 100391). The validated range of concentrations of the
      method was: 0.025-5000 mg l(-1) for RP 57669, RP 54476 and RP 12536 and 0.010
      0.750 mg l(-1) for RP 69012 and RPR 100391.

PMID- 9653959
TI  - High-performance liquid chromatography analysis of Bobel-24 in biological samples
      for pharmacokinetic, metabolic and tissue distribution studies.
AB  - A rapid and simple HPLC method is described for the determination of Bobel-24
      (2,4,6-triiodophenol) and other iodinated derivatives in biological samples. The
      sample preparation was liquid-liquid extraction before injection onto the HPLC
      system. 2,6-Diiodo-4-methylphenol was used as internal standard. Separation was
      obtained using a reversed-phase column under isocratic conditions. The mobile
      phase consisted of water-acetonitrile (62:38). 2,4,6-Triiodophenol was detected
      at 277 nm. This method was used for Bobel-24 determination in plasma, urine,
      synovial liquid and different tissues. The assay was applied to pharmacokinetic
      studies in dog and horse plasma and different dog tissues for tissue distribution
      profiles toxicological and metabolic studies. In addition, this method for
      biological samples can be applied to non-biological samples such as
      pharmaceutical formulations in stability studies and quality control assays.

PMID- 9653960
TI  - Enantioselective analysis of propafenone in plasma using a polysaccharide-based
      chiral stationary phase under reversed-phase conditions.
AB  - We present a method for the enantioselective analysis of propafenone in human
      plasma for application in clinical pharmacokinetic studies. Propafenone
      enantiomers were resolved on a 10-microm Chiralcel OD-R column (250 x 4.6 mm
      I.D.) after solid-phase extraction using disposable solid-phase extraction tubes
      (RP-18). The mobile phase used for the resolution of propafenone enantiomers and
      the internal standard propranolol was 0.25 M sodium perchlorate (pH 4.0)
      acetonitrile (60:40, v/v), at a flow-rate of 0.7 ml/min. The method showed a mean
      recovery of 99.9% for (S)-propafenone and 100.5% for (R)-propafenone, and the
      coefficients of variation obtained in the precision and accuracy study were below
      10%. The proposed method presented quantitation limits of 25 ng/ml and was linear
      up to a concentration of 5000 ng/ml of each enantiomer.

PMID- 9653961
TI  - Simultaneous determination of codeine and its seven metabolites in plasma and
      urine by high-performance liquid chromatography with ultraviolet and
      electrochemical detection.
AB  - A sensitive and selective high-performance liquid chromatography method has been
      developed for the measurement of codeine and its seven metabolites, norcodeine,
      morphine, normorphine, codeine-6-glucuronide, morphine-6-glucuronide, morphine-3
      glucuronide and norcodeine glucuronide, in plasma and urine. The compounds were
      recovered from plasma and urine using solid-phase extraction with C18 cartridges
      and separated on a reversed-phase C8 column with a mobile phase consisting of 77%
      buffer (5 mM sodium phosphate monobasic and 0.70 mM sodium dodecyl sulfate, pH
      2.35) and 23% acetonitrile. Codeine, norcodeine, codeine-6-glucuronide,
      norcodeine glucuronide and morphine-3-glucuronide were detected by ultraviolet
      detection at 214 nm, with a detection limit of 0.02 nmol/ml for each compound in
      plasma. Morphine-6-glucuronide, normorphine and morphine were monitored by
      electrochemical detection at 350 mV, with a detection limit of 0.003 nmol/ml for
      each compound in plasma. The assay showed good reproducibility and accuracy using
      external standardization. The recovery and inter-day variation for all compounds
      in plasma samples were 63.40-77.90% and 3.49-16.77% (R.S.D.) and while in urine
      were 64.98-90.13% and 2.93-9.96% (R.S.D.), respectively.

PMID- 9653962
TI  - Determination of free concentration of sameridine in blood plasma by
      ultrafiltration and coupled-column liquid chromatography.
AB  - Sameridine is a new candidate drug with both local anaesthetic and analgesic
      properties. The free concentration of sameridine in blood plasma was determined
      by coupled-column liquid chromatography. Following adjustment of the pH and the
      temperature of the plasma samples, the free fraction was prepared by
      ultrafiltration. The coupled-column liquid chromatographic system consisted of a
      reversed-phase column, a cation-exchange extraction column and a cation-exchange
      analytical column. Sameridine was detected by UV determination at 205 nm and the
      system showed high selectivity. The limit of quantification was 1 nM and the
      within-day precision was 4.6% (R.S.D., n = 10).

PMID- 9653963
TI  - Simple high-performance liquid chromatographic method with electrochemical
      detection for the simultaneous determination of artesunate and dihydroartemisinin
      in biological fluids.
AB  - A simple, rapid, sensitive, selective and reproducible high-performance liquid
      chromatographic method with reductive electrochemical detection is described for
      the simultaneous quantification of artesunate (ARS) and dihydroartemisinin (DHA)
      in plasma. The procedure involved the extraction of ARS, DHA and the internal
      standard (artemisinin, ARN) with a mixture of dichloromethane and tert.-methyl
      butyl ether (8:2, v/v). Chromatographic separation consisted of the mobile phase
      (acetonitrile-water containing 0.1 M acetic acid, pH 4.8; 45:55, v/v) running
      through the column (Nova-Pak C18, 150 cm x 3.9 mm I.D., 5 microm particle size).
      The retention times of alpha-DHA, beta-DHA, ARS and ARN were 2.9, 4.2, 4.5 and
      6.0 min, respectively. The average recoveries of ARS, alpha-DHA and ARN in the
      concentration range of 10-800 ng/ml were 81.9, 88.2, 101.1 and 84.3%,
      respectively. The coefficients of variation (precision and repeatability) were
      below 10% for all three compounds at concentrations of 50, 200, 400 and 800
      ng/ml, and below 20% at a concentration of 10 ng/ml. The limits of quantification
      for both ARS and alpha-DHA in spiked plasma samples were 5 and 3 ng/ml,
      respectively. The method was found to be suitable for application to
      pharmacokinetic studies of both ARS and DHA.

PMID- 9653964
TI  - High-performance liquid chromatographic method for the determination of the major
      quinine metabolite, 3-hydroxyquinine, in plasma and urine.
AB  - The determination of 3-hydroxyquinine in urine and plasma samples is described.
      Extraction was performed using a mixture of toluene-butanol (75:25, v/v),
      followed by back-extraction into the mobile phase, which consisted of 0.1 M
      phosphate buffer, acetonitrile, tetrahydrofuran and triethylamine. A reversed
      phase liquid chromatography system with fluorescence detection and a CT-sil C18
      column were used. The within-assay coefficient of variation of the method was 2%
      at the higher concentration values in plasma, 2.95 microM, 4% at 227 nM and 9% at
      the lower limit of quantitation, 4.5 nM. In urine, the coefficient of variation
      was 11% at the lower concentration, 227 nM and was 3% at 56.8 microM. The between
      assay coefficient of variation was 4% at the low concentration (5.1 nM) in
      plasma, 2% at 276.8 nM and 3% at 1.97 microM. In urine, the between assay
      coefficient of variation was 4% at 204.6 nM, 3% at 5.12 microM and 2% at 56.8
      microM.

PMID- 9653965
TI  - Reversed-phase high-performance liquid chromatography of 4-(2-pyridyl)-1
      piperazinethiocarboxylic acid 2-[1-(pyridyl)ethylidene]hydrazide dihydrochloride
      (NSC 348977), a synthetic thiosemicarbazone with antitumor activity.
AB  - Reversed-phase HPLC conditions for the separation of 4-(2-pyridyl)-1
      piperazinethiocarboxylic acid 2-[1-(pyridyl)-ethylidene]hydrazide dihydrochloride
      (NSC 348977, I), a synthetic thiosemicarbazone with antitumor activity, from
      mouse plasma have been investigated. Following denaturization and precipitation
      of the spiked plasma with acetonitrile, an aliquot of the supernatant was diluted
      with aqueous buffer and subjected to analysis on a Nova-Pak C18 column (150 x 3.9
      mm I.D.) by isocratic elution with 50 mM aqueous potassium phosphate buffer (pH
      6.8, containing 1 mM EDTA)-acetonitrile (60:40, v/v). The column effluent was
      monitored for UV absorption at 310 nm. Problems identified in the sample
      preparation and separation of I include sensitivity to oxygen, light, non-neutral
      pH and the presence of metal ions. These factors were seen to adversely influence
      sample recovery, and attempts were made to find conditions which minimize their
      effects.

PMID- 9653966
TI  - Development of a highly sensitive high-performance liquid chromatographic method
      for measuring an anticancer drug, UCN-01, in human plasma or urine.
AB  - We have established a highly sensitive high-performance liquid chromatographic
      method for the determination of an anticancer drug, UCN-01, in human plasma or
      urine. Using a fluorescence detector set at an excitation wavelength of 310 nm
      and emission monitored at 410 nm, there was a good linearity for UCN-01 in human
      plasma (r=0.999) or urine (r=0.999) at concentrations ranging from 0.2 to 100
      ng/ml or 1 to 400 ng/ml, respectively. For intra-day assay, in plasma samples,
      the precision and accuracy were 1.8% to 5.6% and -10.0% to 5.2%, respectively.
      For inter-day assay, the precision and accuracy were 2.0% to 18.2% and 2.4% to
      10.0%, respectively. In urine samples, the intra- and inter-day precision and
      accuracy were within 3.9% and +/-2.7%, respectively. The lower limit of
      quantification (LLOQ) was set at 0.2 ng/ml in plasma and 1 ng/ml in urine. UCN-01
      in plasma samples was stable up to two weeks at -80 degrees C and also up to four
      weeks in urine samples. This method could be very useful for studying the human
      pharmacokinetics of UCN-01.

PMID- 9653967
TI  - High-performance liquid chromatography determination of mycophenolic acid and its
      glucuronide metabolite in human plasma.
AB  - Two HPLC-UV assays are reported here: one is a rapid assay for mycophenolic acid
      (MPA) and the other is a simultaneous assay for MPA and its metabolite
      mycophenolic acid glucuronide (MPAG). For both methods, plasma samples (500
      microl) with added internal standard were acidified and extracted using C18 solid
      phase extraction cartridges. Chromatographic separation was achieved on a C18
      Novapak column using a mobile phase consisting of methanol-0.05% orthophosphoric
      acid (40:60, v/v) for the rapid MPA assay and 30:70 for the simultaneous MPA and
      MPAG assay. The assays were linear over the ranges 0.1 to 50.0 mg/l for MPA and
      2.8 to 225.8 mg/l for MPAG. Mean absolute recovery for all analytes was >99%.
      These methods are suitable for therapeutic drug monitoring and pharmacokinetic
      studies.

PMID- 9653968
TI  - Determination of pravastatin in human plasma by high-performance liquid
      chromatography with ultraviolet detection.
AB  - A sensitive high-performance liquid chromatographic (HPLC) method for the
      quantitation of the HMG-CoA reductase inhibitor pravastatin in human plasma is
      described. Sample preparation based on reversed-phase solid-phase extraction
      using triamcinolone acetonide as internal standard (I.S.). The compounds were
      separated on C18 reversed-phase analytical column and then determined by
      ultraviolet detection. The recovery of pravastatin from plasma was 69.2+/-6.7%
      (mean+/-S.D.). The limit of detection for pravastatin in aqueous solution was 0.4
      ng, the limit of quantitation in plasma was 2 ng/ml. In a preliminary
      pharmacokinetic study with two healthy volunteers the t1/2 of pravastatin in
      plasma was found to be 0.8 and 2.3 h.

PMID- 9653969
TI  - Simultaneous determination of the stereoisomers of guggulsterone in serum by high
      performance liquid chromatography.
AB  - Simultaneous separation of E- and Z-guggulsterone, which is the main ingredient
      of 'Guggulip', an ayurvedic drug, was accomplished by HPLC on a C18 column using
      methanol, acetonitrile, buffer and tetrahydrofuran as a mobile phase. The
      compounds were monitored at 248 nm on a photodiode array detector. The assay
      method was used for the simultaneous determination of stereoisomers (E and Z) of
      guggulsterone in spiked serum and dosed (50 mg/kg, p.o.) rats. The recoveries of
      E- and Z-isomers from serum samples were always greater than 90%. The calibration
      graph was linear over the range of 25-2500 ng/ml for Z- and E-isomers. Lowest
      quantitation limit of Z- and E-guggulsterones was 25 ng/ml.

PMID- 9653970
TI  - Determination of flufenamic, meclofenamic and mefenamic acids by capillary
      electrophoresis using beta-cyclodextrin.
AB  - The possibility of separating flufenamic, meclofenamic and mefenamic acids by
      capillary electrophoresis was studied. The best approach involved combining a
      suitable pH of the carrier electrolyte (pH 12.0) with the host-guest complexation
      effects of beta-cyclodextrin. A running buffer consisting of 30 mM phosphate
      buffer (pH 12.0), 2 mM beta-CD and 10% (v/v) acetonitrile was found to provide a
      very efficient and stable electrophoresis system for the analysis of fenamic
      acids by capillary zone electrophoresis. Responses were linear from 0.4 to 40
      microg/ml for the three drugs with detection limits of about 0.3 ng/ml. Intra-
      and inter-day precision values of about 1-2% R.S.D. (n = 11) and 3-4% R.S.D. (n =
      30), respectively, were obtained. The method is highly robust and no breakdowns
      of the current or capillary blockings were observed for several weeks. The
      general applicability of this rapid CZE procedure (migration times less than 12
      min) is demonstrated for several practical samples, including serum, urine and
      pharmaceuticals.

PMID- 9653971
TI  - Comparison of chiral recognition capabilities of cyclodextrins for the separation
      of basic drugs in capillary zone electrophoresis.
AB  - The enantiomeric separation of some racemic anti-histamines and anti-malarials,
      namely (+/-)-pheniramine, (+/-)-brompheniramine, (+/-)-chlorpheniramine, (+/-)
      doxylamine, and (+/-)-chloroquine, was investigated by capillary zone
      electrophoresis. The enantiomeric separation of five compounds was obtained by
      addition of approximately 7 mM (1%, w/v) sulfated-beta-cyclodextrin into the
      buffer as a chiral selector. The effects of sulfated-beta-cyclodextrin
      concentration and buffer pH on migration and resolution are discussed. Two other
      cyclodextrins, carboxyethylated-beta-cyclodextrin and hydroxypropyl-beta
      cyclodextrin were also investigated. Four of the racemic compounds were resolved
      using 14 mM (2%, w/v) carboxyethylated-beta-cyclodextrin while 28 mM (4%, w/v)
      hydroxypropyl-beta-cyclodextrin resolved only two of them. It was found that the
      type of substituent and the degree of substitution on the rim of the CD structure
      played an important role in enhancing the chiral recognition. Cyclodextrins with
      negatively charged substituents and higher degree of substitution on the rim of
      the structure proved to give better resolution to the cationic racemic compounds
      compared with cyclodextrin with neutral substituents. This is due to the
      countercurrent mobility of the negatively charged cyclodextrin relative to the
      cationic analytes thus allowing for a smaller difference in interaction constants
      to achieve a successful resolution of enantiomers. Furthermore, lower
      concentrations of negatively charged cyclodextrins were necessary to achieve the
      equivalent resolutions as compared with the neutral ones.

PMID- 9653972
TI  - Investigation of the stereoselective metabolism of praziquantel after incubation
      with rat liver microsomes by capillary electrophoresis and liquid chromatography
      mass spectrometry.
AB  - Two different separation methods for the antischistosomal drug praziquantel and
      its metabolites by capillary electrophoresis are described. Achiral separation
      was obtained by micellar electrokinetic capillary chromatography using sodium
      dodecyl sulfate as micelle-forming surfactant. On the other hand, the negatively
      charged sulfobutylether-beta-cyclodextrin as a chiral selector enabled the
      separation of the drug and its metabolites as well as their enantioseparation.
      Based on this separation, the enantioselectivity of the metabolism of
      praziquantel was studied by incubation of the drug with rat liver microsomes.
      Whereas trans- and cis-4-hydroxypraziquantel were mainly formed from the R-(-)
      enantiomer, another, different monohydroxylated metabolite was only formed from
      the S-(+)-enantiomer. Information about the structure of these metabolites was
      obtained, using LC-MS.

PMID- 9653973
TI  - Determination of metformin in plasma by capillary electrophoresis using field
      amplified sample stacking technique.
AB  - A capillary electrophoresis method was described for the determination of
      metformin in human plasma based on the extraction of the ion-pair with
      bromothymol blue into chloroform. Phenformin was used as internal standard. Field
      amplified sample stacking injection was employed with an electrokinetic injection
      voltage of 10 kV for 10 s. The running buffer was 0.1 M phosphate buffer (pH
      2.5), running voltage was 20 kV and the UV absorbance detection was set at 195
      nm. The limit of quantitation was 0.25 microg/ml. Linearity range of calibration
      curve was 0.25 to 3.5 microg/ml. Recoveries for three levels (0.25, 1 and 2
      microg/ml) were 80.24%, 67.44% and 58.97% (n = 5 for each level), respectively.
      The intra-day precisions for the three levels were 11.9%, 3.09% and 4.33% and the
      inter-day precisions were 12.4%, 4.57% and 4.94%, respectively. The
      concentrations of metformin hydrochloride in human plasma of eight volunteers
      were measured after orally administrating metformin enteric-capsule and tablet.

PMID- 9653974
TI  - Determination of gamma-glutamylglutathione and other low-molecular-mass
      biological thiol compounds by isocratic high-performance liquid chromatography
      with fluorimetric detection.
AB  - A method was developed for the simultaneous determination of gamma
      glutamylglutathione (gamma-GluGSH) and other low-molecular-mass thiol compounds
      (cysteine, cysteamine, homocysteine, cysteinylglycine, gamma-glutamylcysteine,
      glutathione and N-acetylcysteine) using high-performance liquid chromatography
      combined with precolumn fluorescence labeling with ammonium 7-fluorobenzo-2-oxa
      1,3-diazole-4-sulphonate (SBD-F). These SBD-labeled thiol compounds were
      separated within 35 min on a Cosmosil 5C-18AR column with isocratic elution using
      75 mM sodium citrate buffer (pH 2.90)-methanol (98:2) and detected
      fluorimetrically (ex. 386 nm, em. 516 nm). The calibration graphs using 2
      mercaptoethanol as an internal standard showed good linearity in the range from
      20 pmol to 10 nmol for all thiol compounds examined. The application of this
      method for the quantitative determination of thiol compounds in the urine from
      gamma-glutamyl transpeptidase-deficient mice was also demonstrated. This method
      is sufficiently simple, rapid and sensitive for the determination of gamma-GluGSH
      and other low-molecular-mass thiol compounds in biological samples.

PMID- 9653975
TI  - High-performance liquid chromatographic method for measurement of cytochrome P450
      mediated metabolism of 7-ethoxy-4-trifluoromethylcoumarin.
AB  - An HPLC method for analysis of deethylation of 7-ethoxy-4-trifluoromethylcoumarin
      (ETFMC), a substrate of various enzymes of the cytochrome P450 superfamily, was
      developed. ETFMC was incubated at 37 degrees C with human hepatic microsomes or
      microsomes prepared from a lymphoblastoid cell line that expresses human CYP2B6.
      Under these conditions, the highly fluorescent metabolite 7-hydroxy-4
      trifluoromethylcoumarin (HTFMC) is formed. The metabolite was analyzed by
      reversed-phase HPLC with fluorescence detection. The limits of detection of the
      metabolite were 5.0 fmol per injection, a sensitivity at least one order of
      magnitude greater than the standard method, which does not involve HPLC. This
      method will be of great utility when quantities of microsomal protein from cell
      lines expressing human CYP enzymes are limited.

PMID- 9653976
TI  - Separation of microsomal cytochrome b5 via phase separation in a mixed solution
      of Triton X-114 and charged dextran.
AB  - The successful introduction of a charged dextran into the Triton X-114 phase
      separation system for the selective extraction of cytochrome b5 (cyt. b5) in
      liver microsomes is described. In the absence of charged dextran, 55% of total
      microsomal proteins and 84% of cyt. b5 were extracted into the surfactant-rich
      phase. In the presence of anionic dextran sulfate, the extractability of total
      microsomal proteins was greatly reduced while that of cyt. b5 was increased.
      After triplicate extraction, cyt. b5 was purified more than 10-fold from
      microsomes with a recovery of 91% in the surfactant-rich phase. In view of its
      operational simplicity, this method provides a good means for the partial
      purification of cyt. b5 prior to chromatographic separations.

PMID- 9653977
TI  - Gas chromatographic-mass spectrometric identification and quantitation of benzyl
      alcohol in serum after derivatization with perfluorooctanoyl chloride: a new
      derivative.
AB  - Benzyl alcohol is commonly used as an antibacterial agent in a variety of
      pharmaceutical formulations. Several fatalities in neonates have been linked to
      benzyl alcohol poisoning. Most methods for measuring benzyl alcohol
      concentrations in serum utilize direct extraction followed by high-performance
      liquid chromatography. We describe here a novel derivatization of benzyl alcohol
      using perfluorooctanoyl chloride after extraction from human serum for analysis
      by gas chromatography-mass spectrometry (GC-MS). The derivative was eluted at a
      significantly higher temperature respective to underivatized molecule and the
      method was free from interferences from more volatile components in serum and
      hemolyzed specimens. Another advantage of this derivatization technique is the
      conversion of low-molecular-mass benzyl alcohol (Mr 108) to a high-molecular-mass
      derivative (Mr 504). The positive identification of benzyl alcohol can be
      achieved by observing a distinct molecular ion at m/z 504 as well as the base
      peak at m/z 91. Quantitation of benzyl alcohol in human serum can easily be
      achieved by using 3,4-dimethylphenol as an internal standard. The within run and
      between run precisions (using serum standard of benzyl alcohol: 25 mg/l) were
      2.7% (mean=24.1, S.D.=0.66 mg/l, n = 8) and 4.2% (mean=24.3, S.D.=1.03 mg/l, n =
      8), respectively. The assay was linear for the serum benzyl alcohol
      concentrations of 2 mg/l to 200 mg/l and the detection limit was 0.1 mg/l. We
      observed no carry-over (memory effect) problem in our assay as when 2 microl
      ethyl acetate was injected into the GC-MS system after analyzing serum specimens
      containing 200 mg/l of benzyl alcohol, we observed no peak for either benzyl
      alcohol or the internal standard in the total ion chromatogram.

PMID- 9653978
TI  - Rapid and simple chromatographic method for the determination of diazepam and its
      major metabolites in human plasma and urine.
AB  - A simple, rapid, sensitive and selective HPLC method has been developed for the
      analysis of diazepam (DZP) and its major metabolites, N-desmethyldiazepam
      (DMDZP), temazepam (TZP) and oxazepam (OZP), in plasma and urine, using
      clonazepam (CZP) as the internal standard and chloroform as the extracting
      solvent, with a 10 ng/ml limit of quantitation for the four assayed drugs, and an
      average (+/-S.D.) recovery of 87.7+/-6.46%, 92.9+/-5.31%, 91.4+/-4.01% and 91.7+/
      2.68% for DZP, DMDZP, TZP and OZP, respectively (from plasma), and 89.6+/-2.26%,
      90+/-4.24%, 87.45+/-0.64% and 94.50+/-0.71% for DZP, DMDZP, TZP and OZP,
      respectively (from urine). The method has also proved to be selective and
      reproducible.

PMID- 9653979
TI  - Determination of ethambutol in plasma by high-performance liquid chromatography
      after pre-column derivatization.
AB  - A new HPLC assay using UV detection (200 nm) was developed to determine
      ethambutol (EMB) concentrations in plasma. Following extraction (0.1 ml plasma)
      with chloroform, EMB and octylamine (used as internal standard) were derivatized
      with phenylethylisocyanate. Quantitation in plasma was achieved at 200 nm. There
      were no interferences from endogenous compounds. Intra- and inter-day
      variabilities were lower than 5.2 and 7.6%, respectively. The limit of
      quantitation of the method was 0.2 microg/ml. In plasma, ethambutol was found to
      be stable for at least one month when samples were stored at -20 degrees C. This
      assay was applied to the therapeutic monitoring of EMB concentrations in 19
      patients suffering from tuberculosis.

PMID- 9653980
TI  - Chromatographic studies on the isolation of peroxydisulphate oxidation products
      of primaquine.
AB  - Eight compounds from peroxydisulphate oxidation of primaquine were fractionated
      on Bio-Gel P-2 column using water as an eluent. A HPLC method employing
      acetonitrile-methanol-1 M perchloric acid-water (30:7:1:95, v/v) as a mobile
      phase at 1.0 ml/min on microBondapak reversed-phase column and UV detection at
      254 nm was developed for the separation and identification of different oxidation
      products of primaquine. A combination of Bio-Gel chromatography with reversed
      phase HPLC was found to be the most suitable analytical technique for the
      semipreparative isolation of various products formed from the oxidation. Two
      oxidation products that were isolated had three or four times higher
      gametocytocidal activity as compared to primaquine.

PMID- 9653981
TI  - Colorimetric determination of hydroxyurea in human serum using high-performance
      liquid chromatography.
AB  - A high-performance liquid chromatography assay for hydroxyurea in human serum was
      developed based on a commercial colorimetric assay kit for urea (Sigma
      Diagnostics). Serum (0.5 ml), spiked with methylurea as an internal standard, was
      treated with 70% perchloric acid. Supernatant (0.2 ml) was combined with 0.7 ml
      of BUN acid reagent and 0.6 ml of BUN color reagent. The resulting colored
      reactant (100 microl) was analyzed on a 300 x 3.9 mm Bondclone 10 C18 column
      coupled with a UV-Vis detector, at 449 nm. The mobile phase was 13% acetonitrile
      in water. Retention times of colored derivatives of hydroxyurea and methylurea
      were 6.5 and 12.2 min, respectively. The log-log calibration curve was linear
      from 0.0065 to 1.31 mM. Average accuracy was 99.9+/-4.0% and the intra- and inter
      day error of assay did not exceed 11%.

PMID- 9653982
TI  - High-performance liquid chromatographic determination of propiverine and its N
      oxide in human serum.
AB  - A high-performance liquid chromatographic method has been developed for the
      determination of propiverine hydrochloride (P4) and its main metabolite,
      propiverine N-oxide (P4NO) in human serum. P4 has been shown to be efficacious in
      those patients who have either idiopathic bladder instability, or neurogenic
      bladder (detrusor hyperflexia) resulting from spinal cord injuries. In the
      present method, the analytes were extracted from serum (1 ml, pH 8) into methyl
      tert.-butyl ether. The separation was performed on a reversed-phase C8 (RP-select
      B) column using phosphate buffer-acetonitrile (30:70, v/v). UV absorption was
      used for measuring the analytes, with a limit of quantitation of about 10 ng/ml,
      which is appropriate for pharmacokinetic studies.

PMID- 9653983
TI  - Direct enantioseparation of some beta-adrenergic blocking agents using
      impregnated thin-layer chromatography.
AB  - The resolution of (+/-)-atenolol, (+/-)-propranolol and (+/-)-metoprolol into
      their enantiomers was achieved by TLC on silica-gel plates impregnated with
      optically pure L-lysine (0.5%) and L-arginine (0.5%) as the chiral selectors. In
      all cases, different combinations of acetonitrile-methanol solvent systems were
      found to be successful in resolving these compounds. Spots were detected using
      iodine vapour. The detection limit for both (+/-)-atenolol and (+/-)-propranolol
      was 2.6 microg and for (+/-)-metoprolol, it was 0.26 microg.

PMID- 9653984
TI  - Simple and fast chromatographic method for the determination of sotalol in human
      serum.
AB  - We developed a method for the determination of sotalol in human plasma. After a
      simple deproteinization of the sample, we submit the supernatant to high
      performance liquid chromatography with fluorescence detection. A few minutes are
      necessary to complete the analysis.

PMID- 9653985
TI  - Determination of immuno-cross-reactivity between Cryptosporidium parvum and
      Eimeria spp.
AB  - Immuno-cross-reactivity between Cryptosporidium parvum and Eimeria spp. was
      studied by the indirect fluorescent antibody test (IFAT) and Western blot
      procedure. Thirty-seven sera from asymptomatic (non-diarrheic) cattle, with known
      coprological (presence-absence of coccidia) and serological data respecting C.
      parvum, were tested by IFAT using Eimeria oocysts as antigen. Most sera (54%)
      displayed immunofluorescence around the surface of the Eimeria oocysts.
      Simultaneously, serum samples from rabbits naturally infected with Eimeria spp.
      (E. magna, E. intestinalis and E. residua), but free of C. parvum infection, were
      used to investigate the recognition of C. parvum oocyst antigens by the Western
      blot procedure. Fractions in the 11.5-94 kDa range, as well as others with
      molecular masses over 94 kDa, were recognized by sera from rabbits. Sera
      collected during patency period showed low or moderate reaction with antigenic
      fractions in the 11.5-25 kDa range. However, 29, 58 and 71 to 75 kDa proteic
      fractions were moderately or strongly recognized even after rabbits finished
      oocyst excretion.

PMID- 9653986
TI  - Detection of Blastocystis sp. in domestic dogs and cats.
AB  - Blastocystis sp. was detected in faecal samples from domestic dogs and cats in
      Brisbane, Australia. The prevalence rates were high, with 70.8% of the dogs and
      67.3% of the cats infected with this organism. Blastocystis sp. from faecal
      material from two dogs was successfully cultured on inspissated egg slant medium
      for several months, but could not be maintained for longer periods. Blastocystis
      sp. from feline faecal samples failed to grow in culture. The parasites found in
      dogs and cats were generally smaller than Blastocystis hominis from human faecal
      material, and were the vacuolar form rather than the multivacuolar form.
      Otherwise, the general morphology of these organisms appeared similar to B.
      hominis when examined by light and transmission electron microscopy.

PMID- 9653987
TI  - Ultrastructure of Babesia bigemina gametes obtained in "in vitro" erythrocyte
      cultures.
AB  - Propagation of Babesia bigemina in "in vitro" erythrocyte cultures resulted in
      the appearance of the sexual stage of the parasite, characterized by cytoplasmic
      projections and microtubules. These morphologically distinct parasites were found
      to adhere to each other, with later fusion of their membranes. No nuclear fusion
      was observed. The ultrastructure of the sexual stages was described.

PMID- 9653988
TI  - The safety and efficacy of Australian tick-borne disease vaccine strains in
      cattle in Paraguay.
AB  - Glycerol preserved, frozen tick-borne disease vaccine strains developed in
      Australia were imported into Paraguay to test their safety in pregnant Holando
      heifers and their efficacy against challenge from inoculated local field strains
      of Babesia bigemina, B. bovis and Anaplasma marginale in Hereford X Criolla
      heifers. The two Babesia strains proved to be safe and the B. bovis K strain was
      very effective in providing immunity to a local field strain of B. bovis. The B.
      bigemina efficacy trial was inconclusive, possibly due to the avirulent nature of
      the local field strain used in challenge. The A. centrale strain did not prove to
      be as safe as would be desirable in safety trials, neither did it provide as good
      protection as the Babesia strains in the efficacy trial. It was concluded that
      the Babesia strains provided good protection against field challenge in Paraguay
      and were safe to use in highly susceptible cattle, however an alternative to A.
      centrale should be sought to provide protection against local strains of A.
      marginale.

PMID- 9653989
TI  - Interaction of chicken anaemia virus and Cryptosporidium baileyi in
      experimentally infected chickens.
AB  - The natural occurrence of concomitant chicken anaemia virus (CAV) and
      Cryptosporidium baileyi infection was described earlier. In this experiment, 1
      day-old chickens were infected with CAV alone (anaemia virus infected, AI) or
      followed by inoculation with 8 x 10(5) C. baileyi oocysts orally at 1 wk of age
      (anaemia virus and Cryptosporidium infected, ACI). Another group of chickens
      received the same dose of C. baileyi oocysts without previous virus infection
      (Cryptosporidium infected, CI), and two groups of uninfected chickens served as
      controls. Except one group (uninfected control, UC), all groups -- including the
      other control group (challenged control, CC) -- were challenged with an oral
      inoculum of 8 x 10(5) C. baileyi oocysts at the age of 4 wk. Haematological,
      serological, immunohistochemical and pathological findings confirmed the effect
      of the virus agent. The individual C. baileyi oocyst shedding did not show
      significant difference between group CI and ACI, however, after challenge
      infection the AI chickens shed approximately three times more C. baileyi oocysts
      than those in group CC. Mortality and the percentage of birds that developed
      anaemia was significantly higher among ACI than AI chickens, while haematocrit
      values at 2 wk of age and relative bursal weights at 4 wk of age were moderately
      lower in the ACI group. The results presented here suggest that concurrent CAV
      infection increases the reproductive potential of C. baileyi in chickens, and
      both pathogens have synergistic effect on each other.

PMID- 9653990
TI  - Pharmacokinetics and efficacy of long-term low-level administration of
      triclabendazole in urea molasses blocks against induced bovine and bubaline
      fasciolosis.
AB  - The pharmacokinetics and flukicidal efficacy of triclabendazole delivered in low
      doses on a daily basis through urea molasses blocks were studied in cattle and
      buffaloes experimentally infected with Fasciola gigantica. The observations were
      compared with single therapeutic doses at 12.0 and 24.0 mg/kg body weight in
      cattle and buffaloes, respectively, prior to becoming experimentally infected.
      After receipt of triclabendazole by cattle and buffaloes at 0.83 and 3.0 mg/kg
      body weight, respectively, on a daily basis, both the animal species exhibited
      equilibrium between its absorption and disposition of its metabolites in plasma
      on day 4 and remained almost unchanged thereafter. The continuous subtherapeutic
      dosing of triclabendazole through urea molasses block at 0.83 mg/kg body weight
      in cattle and 3.0 mg/kg body weight in buffalo proved to be efficacious against
      mature liver flukes.

PMID- 9653991
TI  - Observations on the Echinococcus granulosus horse strain in Spain.
AB  - The Spanish sheep and horse strains of Echinococcus granulosus possess several
      differential characteristics in their metacestode stage. Cysts from sheep vary
      widely in size and fertility, but they usually have a thin cyst wall and, when
      fertile, a whitish hydatid sand formed by brood capsules and protoscoleces. Two
      types of infections have been observed in horses: one resembling that of sheep,
      caused by small, non-fertile cysts with a thin wall, and a second type caused by
      medium to large, always fertile cysts with a thick wall. In this latter case,
      hydatid sand is always dark brown in color and formed mainly by brood capsules
      (with almost no free protoscoleces) and abundant calcareous corpuscles. These
      characteristics of the fertile equine cysts, which were identified in other
      studies by genetic, biochemical, immunological and physiological criteria as
      belonging to the horse strain, have not been previously described nor observed in
      cysts from other host species. It is considered that the horse strain possesses a
      strong intermediate host specificity.

PMID- 9653992
TI  - Taenia solium cysticercosis in young pigs: age at first infection and
      histological characteristics.
AB  - In spite of the vast knowledge that exists in the fields of immunology,
      biochemistry, diagnosis and treatment, the basic facts about the dynamics of the
      transmission of Taenia solium are incomplete. The present study determines the
      age at which piglets become infected in a rural community of Mexico, where the
      climate is divided into the dry and rainy seasons. It was found that piglets
      become infected during the dry months, not so during the rainy season. They pick
      up eggs at the age of 2 to 4 weeks and the metacestodes are present in the liver.
      In older animals aged 4 to 6 months, the larvae were also found in the muscles.
      In a 6-month-old pig larvae were found in the muscles and brain. These findings
      may be explained by behavioural studies of free living pigs and climatic
      conditions.

PMID- 9653993
TI  - The effect of repeated moves to clean pasture on the build up of gastrointestinal
      nematode infections in calves.
AB  - The build up of gastrointestinal nematode infections was followed in two grazing
      experiments. Both experiments included four groups of six calves, a permanently
      housed non-infected control group and three groups which were grazed from May to
      October. One of these was moved to aftermath in the beginning of July, the second
      in the beginning of July and August and the third in the beginning of July,
      August and September. The build up of gastrointestinal nematode infections was
      followed by performing faecal egg counts, differentiation of faecal larval
      cultures, pasture larval counts, serum pepsinogen values, serum antibodies
      against Cooperia oncophora, weight gain and worm counts. In the second experiment
      four of the principal trial animals of each group were treated with oxfendazole
      and subsequently challenged with 100,000 larvae of Ostertagia ostertagi to
      examine development of immunity against O. ostertagi. The faecal egg counts and
      the worm counts of the sentinels necropsied in July indicated low initial
      infections in both experiments. Infection levels in experiment 1 remained low in
      each group until the beginning of September. However, during the last month,
      moderate to high infections were acquired by the groups which were moved once or
      twice. In contrast, low to moderate infections were maintained in the group moved
      three times. In the second experiment moderate C. oncophora burdens were already
      observed in the sentinels grazed until the beginning of August. Tracers grazing
      in August-September with the group moved once acquired high O. ostertagi and C.
      oncophora infections, whereas those grazed with both other groups acquired
      moderate infections. In October high infections with both species occurred in the
      groups moved once and twice, whereas low to moderate infections were observed in
      the group moved three times. The challenge infection demonstrated a reduction of
      establishment of O. ostertagi of approximately 70% in all three groups on
      pasture. The results demonstrate that moving calves at monthly intervals to clean
      pasture can be an effective method for the control of parasitic gastroenteritis.
      In addition, the data indicate that it is essential that the last move does not
      occur more than 1 month before the end of the grazing season.

PMID- 9653994
TI  - Pathogenicity and immunogenicity of different isolates of Teladorsagia
      circumcincta.
AB  - The effects on liveweight gain and development of immunity were studied in lambs
      trickle infected for 8 weeks with either a benzimidazole-resistant isolate
      (Moredun ovine resistant isolate, MORI), a multiple benzimidazole + ivermectin
      resistant isolate (Moredun caprine resistant isolate, MCRI) or an unselected
      susceptible isolate (Moredun ovine susceptible isolate, MOSI) of Teladorsagia
      circumcincta. Plasma pepsinogen concentrations of infected groups were
      significantly elevated compared to an uninfected control group (P < 0.001) by day
      14. The liveweight gains varied markedly but there were no statistical
      differences between the infected and uninfected control groups at any point in
      time during the study. Lambs infected with the MORI had significantly lower
      faecal consistency scores than the other challenged groups on days 7 and 14 (P <
      0.05) but from day 21 onwards, faecal consistencies were similar in all of the
      groups. There was a notable difference in the pre-patent periods of the different
      isolates with the MOSI producing positive faecal egg counts (FECs) by day 14 of
      the study. The FECs remained reasonably low once infections had reached patency
      and there were no further differences between the groups. Following
      administration of anthelmintic to remove residual worms from the trickle
      infection, no differences between the infected groups in terms of worm burden or
      mucosal mast cell numbers were evident as a consequence of a single challenge
      infection. The changes in genetic code associated with enhanced resistance
      against anthelmintics do not appear to have resulted in any fundamental
      alteration of the pathogenicity and immunogenicity of these three isolates of
      Teladorsagia.

PMID- 9653995
TI  - Efficacy of ivermectin delivered from a sustained-release bolus against
      gastrointestinal nematodes in field grazing calves in Nyandarua district of
      Kenya.
AB  - The effect of ivermectin delivered by an orally administered prototype sustained
      release (IVM SR) bolus was evaluated over a period of 140 days using 12 steers
      aged approximately 8-10 months and ranging in weight from 150 to 175 kg. They
      were allocated to two groups of 6 steers each by restricted randomization based
      on their liveweight. Each of the treatment group received an IVM SR bolus
      designed to deliver 12 mg of the ivermectin/day for 135 days. The other group was
      designated as non-medicated controls. The groups were placed on adjacent 3 acre
      paddocks obtained by sub-dividing of 6.0 acre permanent pasture which had
      previously been grazed by young untreated cattle so exposing experimental steers
      to a similar challenge of a contaminated paddock. The faecal egg counts, herbage
      larval counts and worm burdens of the major gastro-intestinal nematodes of cattle
      were significantly reduced by the use of the IVM SR boluses. These
      parasitological effects were reflected in the increased liveweight gains in the
      IVM SR bolus-treated steers. The control steers required occasional salvage
      treatments over the trial period and the herbage on their paddock was heavily
      contaminated with infective larvae as reflected in the high worm burden in the
      control steers necropsied at trial termination and in tracer calves introduced
      into the paddocks during the initial (Day 31), interim (Day 69) and final (Day
      100) stages of the experiment.

PMID- 9653996
TI  - The potential of nematophagous fungi to control the free-living stages of
      nematode parasites of sheep: studies with Duddingtonia flagrans.
AB  - The nematophagous fungus, Duddingtonia flagrans, isolated from a fresh sheep
      faecal sample obtained from a farm in northern New South Wales, Australia, was
      subjected to a number of in vivo investigations in both surgically modified and
      normal sheep to determine its capacity to survive passage through the
      gastrointestinal tract. Single and sustained dosing experiments established that
      between 5 x 10(5) and 10(6) chlamydospores/day resulted in a substantial (> 80%)
      reduction in the number of infective larvae derived from nematode eggs in faeces.
      This effect can be maintained if dosing continues. These results demonstrate for
      the first time the potential of nematophagous fungi to be deployed by means of
      sustained release technology in the biological control of nematode parasites of
      livestock.

PMID- 9653997
TI  - The potential of nematophagous fungi to control the free-living stages of
      nematode parasites of sheep: pasture plot study with Duddingtonia flagrans.
AB  - The potential of nematophagous fungi to control the free-living stages of
      nematode parasites of sheep: Pasture plot study with the fungus Duddingtonia
      flagrans. Vet. Parasitol. The experiment was designed to test the ability of D.
      flagrans to reduce infective larval populations on pasture after passage through
      the gastrointestinal tract of sheep. Merino sheep were given chlamydospores by
      intra-ruminal infusion at a rate of 5 million chlamydospores/sheep/day and faeces
      collected from these sheep was deposited on pasture plots. Numbers of larvae
      recovered from faeces and pasture were both lower on plots from sheep dosed with
      fungus (P < 0.001 and P < 0.01, respectively) than on plots from control sheep.

PMID- 9653998
TI  - The relationship between parasite counts, lesions, antibody titres and daily
      weight gains in Psoroptes ovis infested cattle.
AB  - Psoroptes ovis counts, extent of lesions (clinical index: ClinI), daily weight
      gains (DWGs) and anti-P. cuniculi antibody titres in ELISA were recorded during
      seven therapeutic field trials. Relationship between these different data were
      studied. The differences between the mean DWG of treated and untreated control
      animals of the different trials ranged from 39 to 1206 g/day. Data were pooled
      for statistical analysis and the influence of trial conditions (management of the
      herd, farm, treatment) was extracted from each individual data by subtracting,
      from the DWG of each animal, the mean DWG of its trial. Such data were called
      daily weight gain over the trial mean (DWG/TM). Multiple regression of DWG/TM,
      calculated over the period between the clinical examinations in control animals
      (n = 40), on clinical indices and sex demonstrated a significant DWG/TM reduction
      per percentage of affected body surface according to the following equation:
      DWG/TM (in g/day)= 135-22 ClinI(0)-13 ClinI(28/35)-70 (if male) (R2 adjusted =
      0.39), where ClinI(0) and ClinI(28/35) are the clinical indices recorded
      respectively at the beginning (day 0) and at the end (day 28 or 35) of the
      experimental period during which the animals were left untreated. A
      nonsignificant relationship (R2 adjusted = 0.07) was found between the antibody
      titres on day 28 or 35 and the individual DWG/TM This would suggest that serology
      could be used to estimate the prevalence of the disease on a local or national
      basis but not to calculate its economic impact.

PMID- 9653999
TI  - Biometrical alterations of Trypanosoma evansi isolate in laboratory rodents.
AB  - Biometrical alterations in a horse Trypanosoma evansi isolate were observed when
      passaged in laboratory rodents. The major parasite transformation observed was
      the increase in the total length as a consequence of an increase in some parasite
      measurements. These transformations probably occurred as a consequence of a host
      change from horse to rodents. No kinetoplastic forms were observed.

PMID- 9654000
TI  - Outbreaks of trypanosomosis due to Trypanosoma vivax in cattle in Bolivia.
AB  - This paper reports the first occurrence of bovine trypanosomosis due to
      Trypanosoma vivax in Bolivia. T. vivax was identified in thin blood smears of 159
      cattle from the Provinces of Velaco (57), Nuflo de Chavez (20), Guayaros (30) and
      Chiquitos (52), and in 86.20% of 29 cattle from Laguna Concepcion examined by
      microhematocrit test. The clinical signs observed were fever, anemia, abortion,
      progressive weakness, loss of appetite, lethargy, substantial weight loss in a
      relatively short time, and progressive emaciation.

PMID- 9654001
TI  - External anomalies of Anoplocephala perfoliata from remainder of a collection
      from equids in Kentucky with notes on Anoplocephala magna.

PMID- 9654002
TI  - The development of concepts on development--a dialogue with Antonio Garcia
      Bellido. Interview by Enrique Cerda-Olmedo.

PMID- 9654003
TI  - Developmental cell lineage.
AB  - Studies of the role of cell lineage in development began in the 1870s, fell into
      decline in the first half of the 20th century, and were revived in the 1960s.
      This revival was attended by the introduction of new and powerful analytical
      techniques. Cell lineage can be inferred to have a causative role in
      developmental cell fate in embryos in which induced changes in cell division
      pattern lead to changes in cell fate. Such a causative role of cell lineage is
      suggested also by cases where homologous cell types characteristic of symmetrical
      and longitudinally metameric body plan arise via homologous cell lineages. The
      developmental pathways of commitment to particular cell fates proceed according
      to a mixed typologic and topographic hierarchy, which appears to reflect an
      evolutionary compromise between maximizing the ease of ordering the spatial
      distribution of determinants of commitment and minimizing the need for migration
      of differentially committed embryonic cells.

PMID- 9654004
TI  - Creating mosaics in Drosophila.
AB  - The ability to create mosaic animals allows the phenotypic analysis of patches of
      groups of genetically different cells that develop in a wild type environment. In
      Drosophila, a variety of techniques have been developed over the years to
      generate mosaics, and in this chapter, I review the techniques that our
      laboratory has developed. These include the "Dominant Female Sterile" technique
      which allows the analysis of gene functions to oogenesis and embryogenesis; the
      "Gal4-UAS" technique which allows the control of where and when specific genes
      are expressed; and, the "Positive Marked Mutant Lineages" technique which allows
      clones of cells to express a specific reporter gene.

PMID- 9654005
TI  - Probing for gene specificity in epithelial development.
AB  - We surveyed a total of 228 random insertions of a P[GawB] element to determine
      the fraction of regulatory regions in the Drosophila genome that activate gene
      expression specifically in follicle cells versus producing more complex patterns
      of expression. We monitored the GAL4 expression encoded by this construct in the
      ovarian follicle cells by crossing the lines to a strain containing a lacZ
      reporter construct. Sixty four per cent of the insertions showed ovarian
      expression. To assess the specificity of this expression, 124 of the 228 lines
      were crossed to strains containing either an activated form of Armadillo, the
      Drosophila homolog of beta-catenin, or an activated form of Torpedo/Egfr, the
      Drosophila homolog of the Epidermal Growth Factor receptor, under the control of
      GAL4 target sites. The lethality and imaginal disc phenotypes observed in these
      crosses suggest that most random insertions cause GAL4 expression in a variety of
      tissues. Very few insertions appear to drive expression only in follicle cells.
      Although the activated form of Armadillo produced higher frequencies of lethality
      and disk phenotypes, expression in the follicle cell epithelium at later stages
      of oogenesis did not lead to a visible phenotype. This contrasts with the
      dorsalized phenotypes observed in the combination of the same GAL4 lines with the
      activated Torpedo construct.

PMID- 9654006
TI  - Genetic requirement of epidermal and female germ line cells in Drosophila in the
      light of clonal analysis.
AB  - Whether the function of a gene is required in a given cell type is often
      determined through the analysis of clones homozygous for a mutant allele of the
      gene. The clones usually develop following X-ray induced mitotic recombination.
      The paper summarizes the conclusions of clonal analyses of different types of
      mutations in both the epidermis and the female germ line cells of Drosophila.
      Principles of the so called dominant female sterile technique -for the germ line
      and the follicle cells- and its use are summarized. Special attention is paid to
      the genetic requirement of the female germ line due to its fundamental function
      in the regulation of early embryogenesis.

PMID- 9654007
TI  - Cell number control and timing in animal development: the oligodendrocyte cell
      lineage.
AB  - Our studies of oligodendrocyte development in the rodent optic nerve provide
      clues as to how cell numbers and the timing of differentiation may be controlled
      during mammalian development. Both cell number and the timing of differentiation
      depend on intracellular programs and extracellular signals, which together
      control cell survival and cell division. As the cells seem to compete for
      limiting amounts of both survival signals and mitogens, the levels of these
      extracellular signals must be tightly regulated, but it is not known how this is
      achieved. The timing of cell-cycle exit, and therefore the onset of
      differentiation, seems to depend in part on the progressive accumulation of the
      intracellular Cdk inhibitor p27/Kip1, but it is still unclear how the level of
      this protein is controlled over time in the dividing cells. The timing of cell
      cycle exit is also regulated by thyroid hormone, which, along with other
      hormones, seems to coordinate the timing of development in various organs, much
      as the timing of the multiple changes in metamorphosis in both vertebrates and
      invertebrates is coordinated by hormones. In this sense, one might think of
      mammalian development as a prolonged metamorphosis.

PMID- 9654008
TI  - The bHLH genes in neural development.
AB  - Groups of genes sharing similar motifs may be used at different steps of a same
      developmental process. In this review, we discuss the significance of this
      phenomenon in the case of the basic Helix-Loop-Helix (bHLH) proteins that are
      involved at different steps of the development of the peripheral nervous system
      (PNS) of Drosophila.

PMID- 9654009
TI  - The achaete-scute complex as an integrating device.
AB  - A classical model to study pattern formation is provided by the epidermal sensory
      organs (bristles and other sensilla) that cover the body of Drosophila. Many of
      these sensory organs (SOs) arise in very constant positions. How are these
      positions specified? To a large extent, they are defined by the highly resolved
      sites of expression of the proneural genes of the achaete-scute complex (AS-C).
      These genes, which confer to cells the capacity to become SO precursors, attain
      their resolved patterns of expression by means of many position-specific
      enhancers located within the non-transcribed AS-C DNA. Each enhancer drives
      expression at one or very few sites. Evidence is growing that the enhancers
      interact with combinations of activators and repressors (prepattern) distributed
      in partially overlapping domains which are larger than the AS-C expressing sites.
      AS-C transcription is activated only at sites with appropriate combinations of
      factors. Thus, the AS-C integrates the positional information embodied in the
      relatively broad distributions of prepattern factors and creates a sharper and
      topographically more precise pattern.

PMID- 9654010
TI  - Muscle patterning and specification in Drosophila.
AB  - There are obvious differences in the way sense organs and muscles are generated
      during Drosophila embryogenesis. For example, all the cells that compose the
      final sense organ are derived from a unique cell through a well-established
      lineage, whereas each muscle is formed by fusion of myoblasts that belong to two
      different populations: a founder cell and a pool of fusion competent cells.
      Despite these differences, similar genes and mechanisms appear to be involved in
      the generation of the pattern of sense organs and in muscle development. Thus,
      the process of specifying individual cells and endowing them with the ability to
      initiate neuronal or muscle development, as well as the acquisition of
      alternative fates among sibling cells, appear to be under similar genetic control
      both in neural and muscle development.

PMID- 9654011
TI  - The genetics of the Drosophila achaete-scute gene complex: a historical
      appraisal.
AB  - The Drosophila achaete-scute complex consists of four genes encoding
      transcription factors of the bHLH family. Due to their intricate organization,
      these genes have occupied geneticists and developmental biologists for many
      years. Here, genetic studies on the complex are discussed from a historical point
      of view.

PMID- 9654012
TI  - Molecular recapitulation: the growth of the vertebrate retina.
AB  - In postembryonic lower vertebrates, the ciliary marginal zone (CMZ) of the retina
      is a continuously growing zone in the central nervous system. By studying the
      cellular and molecular biology of the cells in this region, we have discovered
      that the CMZ can be divided into several zones, from peripheral to central, which
      reflect different stages of development of retinal stem cells. Based on the
      behavior of the cells and on the genes expressed in different regions, we propose
      here that cellular development in the CMZ recapitulates in space what happens in
      embryonic retinal development in time.

PMID- 9654013
TI  - From pattern to gene, from gene to pattern.
AB  - Our understanding of animal development has been revolutionized by genetic
      approaches to the identification and isolation of pattern-regulating genes. In
      the past several years, fundamental embryological concepts such as morphogenetic
      fields, compartments, and organizers have been defined at a molecular level and
      visualized in developing animals. Here, I will discuss how the focus on the
      regulation and function of genes with dramatic effects on pattern formation,
      primarily by through the analysis of gene expression patterns as surrogates of
      physical pattern elements, has elucidated gene hierarchies that control
      developmental pathways.

PMID- 9654014
TI  - Compartment boundaries: where, why and how?
AB  - In the 1960's, Garcia Bellido and colleagues uncovered the existence of
      developmental compartments in Drosophila. This observation has had a lasting
      impact on our understanding of developmental mechanisms in flies and vertebrates.
      Here, I review the work that demonstrated the existence of compartments. I then
      conjecture on why compartments exist and review the roles of various gene
      products in the maintenance of compartment boundaries.

PMID- 9654015
TI  - Growth and patterning from the engrailed interface.
AB  - The Drosophila wing is divided into anterior and posterior compartments, the
      latter characterized by the expression of the engrailed gene. A comparative
      analysis is presented here, and suggests that a primary conserved role of
      engrailed is to drive growth of limbs along the proximo-distal axis. The Apical
      Ectodermal Ridge in vertebrate limbs resembles the Antero/ Posterior compartment
      boundary in fly wings, particularly in molecular aspects. Multiple evidence
      suggests that the fly wing Antero/Posterior boundary is not the result of
      differential cell affinities between all anterior and posterior cells, but
      responds to the area of cell communication between anterior and posterior
      compartments. Arguments are presented here to support the notion that the
      compartment boundary is a consequence of decapentaplegic function in the control
      of growth. Patterning, on the other hand, requires the participation of several
      genes, among which are engrailed, invected and hedgehog. Finally, regulatory
      interactions between en/En-1 and hh/Shh may be significant in the context of
      morphogenetic regulation during normal development.

PMID- 9654016
TI  - Interactions between Wingless and Notch during the assignment of cell fates in
      Drosophila.
AB  - A large number of observations suggest that, during Drosophila development there
      are close functional interactions between the activity of Notch receptor and that
      of a signaling molecule encoded by wingless gene. In this essay, I summarize
      these interactions and discuss the possibility that Wingless acts as a ligand for
      Notch as part of a switch that is iteratively involved in the assignation of cell
      fates during development.

PMID- 9654017
TI  - Positioning and differentiation of veins in the Drosophila wing.
AB  - Morphogenesis is the process by which structures with characteristic sizes,
      proportions and patterns of cell differentiation are generated during the
      development of multicellular organisms. How the elaboration of pattern is related
      to cell proliferation and growth control is a critical aspect of morphogenesis.
      The imaginal discs of Drosophila are a suitable model in which this can be
      investigated at cellular and molecular level, and recent genetic and
      developmental analysis has identified some of the key genes and mechanisms that
      participate in the regulation of their growth and patterning. This review will
      focus on the formation of the venation pattern in the adult wing, particularly
      on: 1) the subdivision of the wing blade into domains of gene expression that
      position the veins, and 2) the cell-cell signaling pathways that participate in
      the final differentiation of veins.

PMID- 9654018
TI  - Proximo-distal development in the legs of Drosophila.
AB  - The appendages of insects and vertebrates develop as extensions of the body wall.
      During development, a proximo-distal axis for growth and patterning is created in
      each appendage, in order to specify appendage length and allocation of pattern
      elements like joints and sensory organs. Here we use the expression of molecular
      markers to examine how PD development takes place in the legs of the fruit-fly
      Drosophila melanogaster. The data suggest a process of regionalization and
      progressive subdivision of an anlage similar to both insect embryonic
      segmentation and vertebrate somitogenesis.

PMID- 9654019
TI  - Cell proliferation in the attainment of constant sizes and shapes: the Entelechia
      model.
AB  - The Entelechia model is a generative model of morphogenesis where individual
      cells exhibit surface labels that express scalar difference and planar polarity
      along two orthogonal axes X and Y. The amount of surface label depends on the
      level of Martial (M) gene product within each cell. The model assumes that the
      confrontation of cells on both sides of compartment borders causes an increase in
      their level of M gene expression. The resulting disparity between the M value of
      border cells and that of their neighbors induces the latter to divide. After each
      division the daughter cells increase their own M value, and allocate to the best
      matching value position. The increase in M value at the borders therefore extends
      through the anlage in a cascade of proliferation. The Entelechia condition is
      reached when the border cells attain the species-specific maximal M values, and
      the value differences between adjacent cells become indistinguishable. Computer
      simulations reveal that this model accounts for a variety of observations made on
      imaginal discs, e.g., 1) each disc attains a constant size in terms of number of
      cells, independently of the growing conditions; 2) clonal restrictions separate
      populations of cells which proliferate by intercalar growth; 3) dissociated cells
      are capable of reconstructing original patterns upon reaggregation, and 4)
      genetic mosaics of morphogenetic mutations show local effects that may differ
      depending on the position of the mutant cells in the growing anlage.

PMID- 9654020
TI  - Regulatory control of signal transduction during morphogenesis in Drosophila.
AB  - Morphogenesis shapes pattern and size during development. The initiation and
      propagation of morphogenetic processes is led by the integrated activation of
      signaling cascades. Much is known about regulatory control of signaling cascades
      in cell culture systems. However, how this regulatory elements act when cells
      need to behave coordinately is still unknown territory. The morphogenetic process
      of dorsal closure proceeds through changes in cell shape and polarity under the
      control of JNK signaling. Amongst other regulatory elements, Puckered, a
      Drosophila MAPK phosphatase, is involved in a negative feedback loop that
      controls JNK signaling activity. puckered is expressed in many other tissues,
      could influence other developmental events and might regulate different signaling
      cascades. The negative regulatory control of signal transduction pathways could
      be a general mechanism regulating differentiation and morphogenesis.

PMID- 9654021
TI  - Cellular polarity, mitotic synchrony and axes of symmetry during growth. Where
      does the information come from?
AB  - The polarization of cells during development is discussed with relationship to
      synchronized cell divisions and lineage restrictions. A tessellation model is
      proposed to explain the generation of the precise hexagonal array of ommatidia in
      the eye. This model allows the assembly of highly organized structures from
      localized cellular interactions. There is no requirement for a precise genetic
      description of the adult organism. Instead a sequential set of reiterated
      cellular interactions generates increasingly complex structures. The polarity
      patterns observed in adult cuticular bristles and hairs reflect accurate control
      of the shape of terminally differentiating cells rather than fine-grained
      positional information.

PMID- 9654022
TI  - Asymmetry and cell fate in the Drosophila embryonic CNS.
AB  - Drosophila CNS precursors, neuroblasts, repeatedly divide to produce a large
      neuroblast and a smaller GMC. This division is asymmetric with regard to sibling
      cell size, mitotic potential and gene expression. Recent work has identified a
      number of molecules that show a polarized distribution during neuroblast mitosis:
      prospero RNA and Inscuteable, Miranda, Prospero, Staufen, and Numb proteins. The
      process of asymmetric localization of proteins and RNAs is cell cycle dependent,
      microfilament dependent and coordinated with the positioning of the mitotic
      spindle, which results in the unequal distribution of cell fate determinants to a
      specific daughter cell at cytokinesis.

PMID- 9654023
TI  - Segmentation of the vertebrate hindbrain: a time-lapse analysis.
AB  - The chick hindbrain starts from a simple and relatively uniform axis and becomes
      segmented into repeating units, called rhombomeres. The rhombomeres become sites
      of cell differentiation into specific neurons and the location from which neural
      crest cells emerge from the neural tube to form the peripheral nervous system,
      which has only been analyzed at distinct time points due to the lack of a method
      to watch the neural tube as it is shaped into segments. We have developed a whole
      embryo explant culture system in order to study cell and tissue movements with
      time-lapse video microscopy. Quantitative analyses of the neural tube during its
      segmentation show that not all rhombomeres are shaped by the same mechanism. In
      the rostral hindbrain, or first three segments, rhombomeres are shaped by an
      expansion in the lateral width of the mid-rhombomere; either a smaller expansion
      or a constriction takes place at the rhombomere boundaries. In the caudal
      hindbrain, the rhombomere boundaries constrict more than the mid-rhombomere
      lateral widths increase or decrease, leading to the shaping of the segments.
      Throughout the segmentation process the rostrocaudal lengths of all rhombomeres
      remain nearly constant indicating that shape changes are influenced by lateral
      expansions and constrictions of the neural tube.

PMID- 9654024
TI  - Segmentation and specification in the branchial region of the head: the role of
      the Hox selector genes.
AB  - Hox genes are segmentally expressed in the developing vertebrate hindbrain,
      neural crest cells and pharyngeal arches suggesting an important role in
      patterning these structures. Here we discuss the cellular and molecular
      mechanisms controlling segmentation and specification in the branchial region of
      the head. In addition, based on the recent phenotypical and molecular analysis of
      loss-of-function mutants in the mouse, we speculate that Hox genes may act like
      Drosophila selector genes in this system.

PMID- 9654025
TI  - The bithorax complex: the first fifty years.

PMID- 9654026
TI  - From selectors to realizators.
AB  - In 1975 Antonio Garcia-Bellido proposed a framework for understanding the
      morphogenetic function of homeotic genes in terms of selector genes and
      realizator genes. Since then, much has been learnt of the molecular nature and
      expression patterns of the Hox selector genes. Our identification of realizator
      genes, and our understanding of how specific sets of realizators are activated in
      different segments, is still far from complete, however. Here we discuss the
      nature of the Hox target genes identified so far and the basis of the target
      specificity of Hox gene products.

PMID- 9654027
TI  - trithorax and the regulation of homeotic gene expression in Drosophila: a
      historical perspective.
AB  - Animals homozygous for a spontaneously arising allele of the trithorax (trx) gene
      exhibit highly variegated homoeotic transformations of their thoracic and
      abdominal segments. This paper retraces the sometimes tortuous history of the
      analysis of trx function, from the fortuitous recovery of the first trx allele,
      to the present understanding that trx encodes a highly conserved chromatin
      binding protein that is required to maintain the expression of the Antennapedia
      and Bithorax complex genes.

PMID- 9654028
TI  - Homeotic proboscipedia cell identity functions respond to cell signaling pathways
      along the proximo-distal axis.
AB  - To better understand how the different cell identities composing a segment are
      attributed and coordinated under the control of a single homeotic selector gene,
      we examined dose-sensitive homeotic phenotypes associated with gain-of-function
      and loss-of-function mutations of the homeotic gene proboscipedia (pb; Hox-A2/
      B2). We then employed dose-sensitive segment and cell identity phenotypes
      resulting from ectopic proboscipedia expression to screen for other interacting
      loci. We find that pb, as well as the homeotic loci Ultrabithorax, Sex combs
      reduced and Antennapedia, respond to positional information along the proximo
      distal axis. This response for pb implicates at least two signal transduction
      pathways, those involving Ras1 and Notch.

PMID- 9654029
TI  - Implications of the spatial and temporal regulation of Hox genes on development
      and evolution.
AB  - Nearly 20 years have passed since Ed Lewis revealed the importance of Hox genes
      in the specification of different segments in the anterior-posterior axis of the
      fly. Pioneering studies by several authors, among others Garcia-Bellido and his
      student Gines Morata, helped to elaborate a theory of segmental specification
      that was strengthened with the arrival of molecular techniques to the field of
      Developmental Biology. The conservation of Hox genes in metazoans at the level of
      sequence, function and complex organization has resulted in the export of this
      Drosophila theory as a paradigm to interpret the development of axial
      specification in organisms less amenable to experimental study. There are two
      main ways to interpret how Hox genes work in Drosophila. One considering Hox
      genes as "segment identity" factors giving global properties to the segments in
      which they are active. Another considering Hox genes as encoding spatially
      restricted transcription factors required for a number decisions taken at the
      cellular level. Here I use published and unpublished experimental data to
      illustrate that early activation of the Hox genes does not establish a gene code
      that leads to "segment identity". I will stress the point that Hox expression
      patterns develop with the embryo, that there are many genes involved in this
      modulation, and that the changing pattern of expression is important to achieve
      the final shape of the animal. I will show that, by interpreting Hox gene
      function in this way, some apparently paradoxical results in the Hox field can be
      answered. Finally, I discuss the implications of dynamic Hox gene expression on
      the evolution of segment morphology.

PMID- 9654030
TI  - Hox genes, homeosis and the evolution of segment identity: no need for hopeless
      monsters.
AB  - Significant changes have occurred in the developmental role of Hox genes, even
      within groups of arthropods that already have complex body plans and many
      different segment types. This is hard to reconcile with the 'selector gene' model
      for Hox gene function. Selector genes act as stable binary switches that direct
      lineages of cells to adopt alternative developmental fates. This model suggests
      that the regulation of selector genes can only evolve through mutations that
      alter the identity of whole developmental compartments -in the case of Hox genes,
      whole segments. Once segments have evolved distinct morphology and function, such
      mutations will result in dramatic homeotic transformations that are unlikely to
      be tolerated by natural selection. Thus we would expect the developmental role of
      these "master control genes" to become frozen as body plans become more complex.
      I argue for a revised model for the role and regulation of the Hox genes. This
      provides alternative mechanisms for evolutionary change, that may lead to
      incremental changes in segment morphology. The summation of such changes over
      long periods of time would result in differences in Hox gene function between
      taxa comparable to the effects of gross homeotic mutations, without the need to
      invoke the selective advantage of hopeful monsters.

PMID- 9654031
TI  - Understanding the genetic basis of morphological evolution: the role of homeotic
      genes in the diversification of the arthropod bauplan.
AB  - Due to the segmental organization of their body plans, arthropods can be
      considered the paradigmatic modular organisms. In the past two decades, genetic
      studies of the homeotic (Hox) genes in Drosophila melanogaster have provided
      initial insight into the molecular mechanisms that govern the establishment of
      segmental identity. In this review, we will address the question of the possible
      role of four Hox genes: labial (lab), proboscipedia (pb), Deformed (Dfd), and Sex
      combs reduced (Scr) in the morphological evolution of arthropods, particularly
      with respect to the evolution of the head and head structures in insects.
      Overall, these preliminary studies illustrate the role that some of the Hox genes
      expressed in the insect head have played in the morphological evolution of
      hexapods and likely arthropods in general.

PMID- 9654032
TI  - Genesis versus epigenesis: the odd jobs of the Polycomb group of genes.
AB  - Cells need the products of the Polycomb Group of genes (PcG) to keep, through
      development, the memory of their genetic determination. The pleiotropic mutant
      phenotypes of PcG genes strikingly resemble morphological traits, considered as
      taxonomic characters with phylogenetic meaning, used in Dipteran classification.
      I argue that spatial modulation of the multimeric complexes formed by PcG
      products has played a role or escorted the genesis of species.

PMID- 9654033
TI  - Sir Vincent Wigglesworth and the coming of age of insect development.
AB  - Sir Vincent Wigglesworth (1899-1994), a founder of the discipline of Insect
      Physiology, was a central figure in the emergence of the concept of postembryonic
      insect development as sequential polymorphism regulated by endocrine signals. At
      a time in mid-century when genetics and developmental physiology were severely
      compartmentalized, he made the conceptual linkage with the recognition that
      sequential polymorphism must have a genetic basis with gene activation regulated
      by internal signals.

PMID- 9654034
TI  - Embryonic development as a quasi-historical process.
AB  - This essay explores the nature of embryonic development in contrast to other
      kinds of processes. Anhistorical processes are highly reproducible and are
      therefore subject to standard scientific analysis. Such analyses yield results
      that may well apply universally. Euhistorical processes are non-reproducible.
      Therefore they are not subject to standard scientific analysis, but are
      investigated primarily by retrospective speculation. Information gained from such
      analyses is of relatively limited applicability. Embryonic development exhibits
      traits associated with both anhistorical and euhistorical processes and is
      therefore defined as a quasi-historical process. The quasi-historical nature of
      developmental processes places constraints on the nature of the solution we can
      hope to obtain for the problem of development, but also provides a means of
      exploring the euhistorical process of evolution.

PMID- 9654035
TI  - Laws for the dynamics of regulatory networks.
AB  - We start our analysis from historical but too seldom quoted papers by Delbruck,
      Noveck & Weiner, Cohn & Horibata and Monod & Jacob. We try to show how it became
      possible to draw a line coupling cell differentiation to the physical concept of
      multistationarity, and the latter to the concept of positive feedback circuits.
      Two laws give the minimal logical ingredients required for differentiative and
      homeostatic regulations. It is briefly shown how they can be used to treat such
      complex dynamics as deterministaic chaos, which, admittedly, does not yet belong
      to the corpus of developmental biology. It was taken as a challenge to express
      our ideas here in purely verbal terms, avoiding any formal treatment.

PMID- 9654036
TI  - Syntagms in development and evolution.
AB  - The genetic analysis of segmentation, neurogenesis, appendage formation and other
      developmental processes has revealed that the development of Drosophila can be
      broken down into discrete elementary operations. Thus development can be viewed
      as a stepwise process where each step is driven by a small group of genes working
      interactively. Garcia-Bellido proposed that each of these groups be called a
      "syntagm". In this review, we will describe a series of developmental syntagms,
      and explore the consequences of this discontinuous organization of the
      developmental program on evolution.

PMID- 9654037
TI  - How is developmental stability sustained in the face of genetic variation?
AB  - The number and arrangement of scutellar bristles on the thorax of Drosophila
      melanogaster is largely invariant in wild-type stocks. This character therefore
      appears to be buffered against changes in phenotype, and has previously been
      described as a canalized character. Mutations that do alter this phenotype
      increase the variability in bristle number and can reveal otherwise cryptic
      genetic differences at other loci. This phenomenon is examined and possible
      mechanisms contributing to stability of this developmental event are discussed,
      but the notion that the character is canalized is found not to be heuristic.

PMID- 9654038
TI  - Seven types of pleiotropy.
AB  - Pleiotropy, a situation in which a single gene influences multiple phenotypic
      traits, can arise in a variety of ways. This paper discusses possible underlying
      mechanisms and proposes a classification of the various phenomena involved.

PMID- 9654039
TI  - Making sense of behavior.
AB  - Neurobiological evidence shows that, during the development of the nervous
      system, inherited behavioral sense is built into the brain with remarkable
      fidelity. However the way in which the underlying circuitry and its functional
      characteristics are represented in the genome is not well understood. One
      response to this is to investigate the machinery of functional development in the
      nervous system and to set down in principle how genetic control is exerted at
      this level.

PMID- 9654040
TI  - Debatable issues. Interview by Alain Ghysen..
AB  - This paper reports a discussion between Antonio Garcia-Bellido and Lewis Wolpert
      about a number of questions raised by Alain Ghysen. The questions follow, in
      reverse order, the subjects dealt with in this issue: first the principles (are
      there unifying principles of development?), then questions dealing with evolution
      (why are patterns conserved?) and with the homeotic genes (what is their
      function?), then the cell biology of development (who is controlling actual
      morphogenesis?), and the generation and evolution of patterns (what makes
      development so reproducible and how does it change from one species to another?)
      and finally about the genetics of cell determination and specification (how does
      a cell measure its position?). Obviously the discussion did not provide any firm
      answers to any of these questions. Perhaps more importantly, it provides a vivid
      picture of two contrasting ways of thinking about developmental problems.

PMID- 9654041
TI  - Antonio Garcia-Bellido at Hadorn's laboratory in Zurich.

PMID- 9654042
TI  - Antonio Garcia-Bellido in Caltech.

PMID- 9654043
TI  - Antonio and Sturt: an interaction.

PMID- 9654044
TI  - An exceptional friend.

PMID- 9654045
TI  - Serendipity, the principle of limited sloppiness, and neural development.

PMID- 9654046
TI  - The genetic logic of Antonio Garcia-Bellido.

PMID- 9654047
TI  - In defense of pure science: Antonio Garcia-Bellido.

PMID- 9654048
TI  - Regulation of translation initiation factors by signal transduction.
AB  - Regulation of eukaryotic translation initiation is a process that requires
      collaboration between multiple proteins. The cap-binding factor eukaryotic
      initiation factor (eIF)4E, its binding protein 4E-BP1, and the guanine-nucleotide
      exchange factor eIF2B play important roles in the regulation of the rate of
      protein synthesis. This review describes the regulation of the activity of these
      three proteins and the signal-transduction pathways involved therein.

PMID- 9654049
TI  - Mitogen-activated protein kinase is involved in epidermal-growth-factor-regulated
      protein phosphorylation in nuclear membranes isolated from JEG-3 human
      choriocarcinoma cells.
AB  - The treatment of highly purified nuclear membranes isolated from JEG-3 human
      choriocarcinoma cells with epidermal growth factor (EGF) resulted in an increase
      of the receptor autophosphorylation and the phosphorylation of several other
      proteins, including 44-kDa, 34-kDa and 24-kDa proteins, and a decrease in the
      phosphorylation of a 40-kDa protein. The kinetics of phosphorylation and the use
      of RG-13022, a selective inhibitor of EGF-receptor kinase activity, suggested
      that receptor activation was necessary for the phosphorylation response of the
      other proteins. Tyr was exclusively phosphorylated in the EGF receptor and 24-kDa
      proteins, Tyr and Thr were phosphorylated in the 44-kDa protein, and Ser was
      phosphorylated in the 34-kDa protein and dephosphorylated in the 40-kDa protein.
      The molecular size, Thr/Tyr phosphorylation, immunoprecipitation and enzymatic
      activity towards myelin basic protein suggested that the 44-kDa protein was a
      mitogen-activated protein (MAP) kinase. The EGF treatment not only increased
      phosphorylation but also catalytic activity of MAP kinase and these increases
      were prevented by the addition of RG-13022. In summary, this report demonstrates
      that target cell nuclei contain EGF receptors, which use the MAP kinase signaling
      pathway.

PMID- 9654050
TI  - A plant surface protein sharing structural properties with animal integrins.
AB  - Using a polyclonal antibody (P23) generated against the human platelet integrin
      aIIb beta3 and a FITC-conjugate secondary antibody, fluorescence is observed at
      the surface of protoplasts isolated from Arabidopsis thaliana and Rubus
      fruticosus. Arabidopsis thaliana cells grown in suspension culture containing P23
      and glycylarginylglycylaspartylserine (GRGDS), a synthetic peptide containing the
      RGD sequence found in many extracellular matrix adhesive proteins demonstrated
      aberrant cell wall/plasma membrane interactions and organization. When
      glycoproteins from these plants, purified on a concanavalin A Sepharose 4B, were
      subjected to SDS/PAGE and Western blotting, under reduced and non-reduced
      conditions, immunoblots probed with P23 revealed bands in both species. A shift
      in electrophoretic mobility is observed to different apparent molecular mass when
      no reducing agent is present. When purified by immunoaffinity chromatography on
      anti-aIIb beta3 Sepharose or Sepharose linked to the synthetic peptide D-Arg-Gly
      Asp-Trp, the major antigenic components detected migrate at 30 kDa and 60 kDa in
      the first experiment and 60 kDa in the second one. Only the 60-kDa component is
      immunodetected with antibodies specific for either the beta3 platelet chain or
      the aIIb polypeptide, suggesting the presence of two polypeptides co-migrating.
      To address more precisely the structure of this complex in plants, competition
      assays were performed. A significant inhibition is observed with CS3 a monoclonal
      antibody that interacts with the complexed form aIIb beta3 but not the
      dissociated subunits. Further structural similarities with the animal aIIb beta3
      complex is demonstrated with Western blotting detection after plant glycoproteins
      immunoprecipitation with CS3 in absence or presence of 5 mM EDTA to dissociate
      the complex. We also present data on the characterization of a polyclonal
      antibody, named AcAt2, raised against Arabidopsis glycocoproteins purified by
      affinity chromatography on a D-RGDW column and eluted with the same peptide, that
      specifically interacts with the animal aIIb beta3 receptor.

PMID- 9654052
TI  - Processing and release of tumor necrosis factor alpha.
AB  - Tumor necrosis factor alpha (TNFalpha) is synthesized as a transmembrane
      precursor form that is proteolytically processed and released as the soluble
      mature form. In human monocytes and monocytic cell lines, the production,
      processing, and release of TNFalpha are co-induced by certain activators, such as
      lipopolysaccharide. To investigate the mechanism of TNFalpha processing and
      release, we established a cell line which constitutively produced TNFalpha, by
      transfecting the TNFalpha precursor form cDNA into NIH/3T3 cells. In these cells,
      the processing and release of TNFalpha were augmented by phorbol 12-myristate 13
      acetate (PMA), mediated through a protein kinase C (PKC) signalling pathway.
      Various protease inhibitors were tested and it was found that matrix
      metalloproteinase (MMP) inhibitors blocked the processing and release of TNFalpha
      both in the absence and presence of PMA. This result is compatible with the
      recent reports that MMP are involved in the processing and release of TNFalpha.
      In contrast, 3,4-dichloroisocoumarin, N alpha-p-tosyl-L-phenylalanine
      chloromethane, iodoacetamide, and o-phenanthroline inhibited the processing and
      release of TNFalpha only in the presence of PMA, suggesting that serine proteases
      requiring SH for their activity, a combination of serine proteases and cysteine
      proteases, or MMP, may be involved in the PKC-mediated induction of TNFalpha
      processing and release.

PMID- 9654051
TI  - Identification of Man alpha1-3Man alpha1-2Man and Man-linked phosphate on O
      mannosylated recombinant leech-derived tryptase inhibitor produced by
      Saccharomyces cerevisiae and determination of the solution conformation of the
      mannosylated polypeptide.
AB  - The production of recombinant leech-derived tryptase inhibitor (rLDTI) by two
      different strains of Saccharomyces cerevisiae resulted in the secretion of non
      glycosylated and glycosylated rLTDI. Monosaccharide analysis and a-mannosidase
      treatment demonstrated that glycosylated rLDTI was exclusively alpha
      mannosylated. A trypsin digest of reduced and S-carboxymethylated glycosylated
      rLDTI was separated on a reverse-phase HPLC column. Glycopeptides identified by a
      combination of matrix-assisted laser desorption mass spectrometry, amino acid
      sequence analysis, and monosaccharide analysis revealed the presence of different
      glycoforms. It was found that Ser24, Ser33 and Ser36 were partially glycosylated
      with a single mannose residue, whereas Thr42 in glycosylated rLDTI from both
      strains was fully occupied with manno-oligosaccharides with a degree of
      polymerization ranging over 1-3 and 1-13 depending on the yeast strain. In
      phosphorylated rLDTI a single phosphate group was predominantly located at the
      innermost Man residue of units of mannobiose, mannotriose, mannotetraose and
      mannopentaose at Thr42. Oligosaccharides released by alkaline treatment were
      reduced by sodium borohydride and separated by high-pH anion-exchange
      chromatography on a CarboPac MA1 column, and analyzed by one- and two-dimensional
      1H-NMR spectroscopy. Besides the major oligosaccharide Man alpha1-2Man-ol, the
      (for yeast protein O-glycosylation) unusual Man alpha1-3Man alpha1-2Man-ol was
      determined. The solution conformation of glycosylated rLDTI was investigated by
      two-dimensional NMR spectroscopy. Structure calculations by means of distance
      geometry showed that glycosylated rLDTI is compactly folded and contained small
      secondary structure elements. Analysis of the chemical shifts showed that amino
      acids Val32-Ser33, Ser36-Ser39 and Thr42 were affected by the O-mannosylation. In
      addition, changes in chemical shift were observed within the beta-hairpin peptide
      regions Val13-Ser16 and Gly18-Tyr21 attributed to direct interactions of the
      mannose residue at Ser36. Furthermore, the protein-linked oligosaccharides were
      spatially grouped in a position opposite of the canonical binding loop.

PMID- 9654053
TI  - Biochemical characterization and localization of transglutaminase in wild-type
      and cell-death mutants of the nematode Caenorhabditis elegans.
AB  - Transglutaminase activity was characterized in extracts of the nematode
      Caenorhabditis elegans using a microtiter plate method, and found to be Ca2+
      dependent, optimal at pH 8.0, and to be inhibited by EGTA, ammonia, iodoacetamide
      and GTP. Monoclonal and polyclonal antibodies raised against human tissue
      transglutaminase also inhibited the activity and detected a 61-kDa protein from
      the worm lysate. Constitutive expression of the enzyme in the wild-type
      intestinal cells was revealed by immunohistochemistry. Potential protein
      substrates for the enzyme were found in worm lysates using a biotin-labelled
      amine substrate. There is a basal level of protein-bound epsilon(gamma
      glutamyl)lysine cross-links, characteristic of transglutaminase activity, formed
      in situ in adult wild-type animals. Developmental studies have revealed that the
      enzyme activity is highest in adult animals, and relatively higher in L1 larvae
      than in other larval stages. As compared to wild types, lower transglutaminase
      activity has been measured in lysates of ced-3, ced-4 and ced-9 mutants. Cross
      link levels were also low in ced-4 and ced-9 mutants. By contrast, the crosslink
      content was high in several phagocytosis mutants. The highest concentration was
      found in the ced-5; ced-7 double phagocytosis mutants which carry an extra number
      of dead cells during their lifespan. In accordance with this finding, several
      transglutaminase-immunopositive cells were found in both the embryos and in the
      head of these double phagocytosis mutants. The results suggest that a
      transglutaminase is involved in, or related to, the death program of cells in C.
      elegans and the expression and crosslinking activity of the enzyme may be
      perturbed in some ced mutants.

PMID- 9654055
TI  - Engineering of factors determining alpha-amylase and cyclodextrin
      glycosyltransferase specificity in the cyclodextrin glycosyltransferase from
      Thermoanaerobacterium thermosulfurigenes EM1.
AB  - The starch-degrading enzymes alpha-amylase and cyclodextrin glycosyltransferase
      (CGTase) are functionally and structurally closely related, with CGTases
      containing two additional domains (called D and E) compared to the three domains
      of alpha-amylases (A, B and C). Amino acid residue 196 (Thermoanaerobacterium
      thermosulfurigenes EM1 CGTase numbering) occupies a dominant position in the
      active-site cleft. All alpha-amylases studied have a small residue at this
      position (Gly, Leu, Ser, Thr or Val), in contrast to CGTases which have a more
      bulky aromatic residue (Tyr or Phe) at this position, which is highly conserved.
      Characterization of the F196G mutant CGTase of T. thermosulfurigenes EM1 revealed
      that, for unknown reasons, apart from the F196G mutation, domain E as well as a
      part of domain D had become deleted [mutant F196G(delta'DE)]. This, nevertheless,
      did not prevent the purification of a stable and active mutant CGTase protein (62
      kDa). The mutant protein was more similar to an alpha-amylase protein in terms of
      the identity of residue 196, and in the domain structure containing, however,
      some additional C-terminal structure. The mutant showed a strongly reduced
      temperature optimum. Due to a frameshift mutation in mutant F196G, a separate
      protein of 19 kDa with the DE domains was also produced. Mutant F196G(delta'DE)
      displayed a strongly reduced raw-starch-binding capacity, similar to the
      situation in most alpha-amylases that lack a raw-starch-binding E domain.
      Compared to wild-type CGTase, cyclization, coupling and disproportionation
      activities had become drastically reduced in the mutant F196G(delta'DE), but its
      saccharifying activity had doubled, reaching the highest level ever reported for
      a CGTase. Under industrial production process conditions, wild-type CGTase
      converted starch into 35% cyclodextrins and 11% linear oligosaccharides (glucose,
      maltose and maltotriose), whereas mutant F196G(delta'DE) converted starch into
      21% cyclodextrins and 18% into linear oligosaccharides. These biochemical
      characteristics indicate a clear shift from CGTase to alpha-amylase specificity.

PMID- 9654054
TI  - A domain within the tumor suppressor protein APC shows very similar biochemical
      properties as the microtubule-associated protein tau.
AB  - The tumor-suppressor protein APC (adenomatous polyposis coli) binds to
      microtubules and promotes tubulin assembly. In vivo the endogenous APC protein is
      mainly localized at the end of microtubules that are involved in active cell
      migration. Since most tumor-specific APC gene mutations lead to the loss of the
      microtubule binding domain this interaction is assumed to play a crucial role in
      tumorigenesis. In this study we show that an APC protein fragment (amino acids
      2219-2580) within the C-terminal part is enough to bind to non-assembled tubulin
      with high affinity. The binding of APC to tubulin does not lead to an alteration
      of the intrinsic GTPase activity of the non-assembled tubulin. The APC protein
      induces the tubulin assembly in a fast reaction and below the critical assembly
      concentration of tubulin. The APC protein induces the bundling of the assembled
      microtubules in a concentration-dependent manner. Regarding its biochemical
      properties the analysed APC protein fragment strikingly resembles the members of
      the microtubule-associated protein family tau. This analogy may help to
      understand the role of the APC protein in the suppression of tumorigenesis.

PMID- 9654056
TI  - Thylakoid membranes contain a high-conductance channel.
AB  - Ion channels in the thylakoid membrane were investigated by direct patch clamping
      on swollen thylakoids. A preparation method has been developed in order to
      release osmotically swollen intact thylakoids from pea protoplasts derived from
      cotyledons of young Pisum sativum plants. The swollen thylakoids with typical
      diameters between 10 microm and 20 microm formed reproducibly high-resistance
      seals with patch pipettes. We observed a potassium channel with a main conductant
      state of lambda approximately 40 pS and a conductance of lambda approximately 90
      pS (in asymmetric 20/100 mM KCl) for the fully open channel. Surprisingly, the
      thylakoid membranes also contained a high-conductance channel with a main
      conductant state of lambda approximately 620 pS (in asymmetric 20/100 mM KCl),
      revealing also higher and lower conductant states. With a different experimental
      approach we showed that thylakoids are able to accumulate transiently the
      membrane impermeant fluorescent dye Lucifer Yellow which likewise suggests the
      presence of a pore-like channel with a diameter large enough to allow permeation
      of Lucifer Yellow.

PMID- 9654057
TI  - Carnitine palmitoyltransferase II specificity towards beta-oxidation
      intermediates--evidence for a reverse carnitine cycle in mitochondria.
AB  - Using isolated rat liver mitochondria, in the absence or presence of malonyl-CoA
      (an inhibitor of carnitine palmitoyltransferase I), we have found that carnitine
      palmitoyltransferase II (CPT II) is active with palmitoyl-CoA as well as with its
      beta-oxidation intermediates. A partially purified CPT II fraction from rat liver
      mitochondria was shown to be able to convert 3-hydroxypalmitoyl-CoA to 3
      hydroxypalmitoylcarnitine, which could be identified by fast-atom-bombardment
      mass spectrometry. This apparent broad specificity of CPT II was further
      evaluated by kinetic studies using purified CPT II. It was found that CPT II
      readily accepts 3-oxopalmitoyl-CoA, palmitoyl-CoA, 3-hydroxypalmitoyl-CoA and 2,3
      unsaturated palmitoyl-CoA as substrates with decreasing order of affinity. The
      apparent Vmax values found for the first three compounds were of the same order
      of magnitude; the 2,3-unsaturated acyl-CoA was the poorest substrate. Kinetic
      studies with purified CPT II showed 3-hydroxypalmitoyl-CoA to have the lowest
      K0.5 value (20 +/- 6 microM) of all the CoA esters studied; the highest K0.5
      value (65 +/- 17 microM) was found for the 3-oxo intermediate. These findings
      support the hypothesis that CPT II is involved in the export of toxic long-chain
      acyl-CoA esters from the mitochondria by first converting them into the
      corresponding carnitine esters, followed by transport out of the mitochondria and
      subsequently out of the cell.

PMID- 9654058
TI  - Glucocorticoids induce the expression of the leptin gene through a non-classical
      mechanism of transcriptional activation.
AB  - Leptin is a hormone which is produced in adipose tissue and which plays a role in
      the regulation of energy homeostasis. The expression of the ob gene, encoding
      leptin, is under multi-hormonal control. We have shown previously that high doses
      of glucocorticoids are positive regulators of leptin expression in rats and that
      they concomitantly reduce food intake and body mass gain in these animals. In the
      present report we analyse the molecular mechanism of this glucocorticoid
      regulation of leptin expression. In cultured rat adipocytes dexamethasone induces
      leptin mRNA levels, an effect not inhibited by the protein synthesis inhibitor
      cycloheximide. In addition, our data indicate that the induction of the
      expression of the leptin gene by dexamethasone is at least in part due to a
      transcriptional activation that is mediated by the glucocorticoid receptor.
      Deletion mapping of the human leptin promoter shows that cis-elements involved in
      the glucocorticoid effect are located between -55 and +31 relative to the
      transcription initiation site. Since this region does not contain a binding site
      for the glucocorticoid receptor, the effect does not rely on the classical
      molecular mechanism of glucocorticoid receptor action. A role of C/EBP and Sp-1
      in mediating this glucocorticoid effect was furthermore excluded. Multiple
      nuclear factors from 3T3-L1 preadipocytes interact with this promoter region of
      the human leptin gene and may be potential mediators of the induction by
      glucocorticoids.

PMID- 9654059
TI  - Dicyclohexylcarbodiimide interaction with the voltage-dependent anion channel
      from sarcoplasmic reticulum.
AB  - In a recent study [Shoshan-Barmatz, V., Orr, I., Weil, S., Meyer, H., Varsanyi,
      M. & Heilmeyer, L. M. G. (1996) FEBS Lett. 386, 205-210] we have demonstrated the
      presence of the voltage-dependent anion channel (VDAC) in skeletal muscle
      sarcoplasmic reticulum (SR) as supported here by co-localization of VDAC and
      (Ca2+ + Mg2+)ATPase in the SR using double-immunogold labeling. The interaction
      of the carboxyl-modifying reagent dicyclohexylcarbodiimide with the SR-VDAC is
      characterized by labeling with [14C]dicyclohexylcarbodiimide and by
      dicyclohexylcarbodiimide modification of the reconstituted-purified VDAC channel
      activity. In both SR and mitochondrial membranes, [14C]dicyclohexylcarbodiimide
      most specifically labeled a 35-kDa protein, identified as VDAC by specific anti
      VDAC Ig. Labeling of the SR-VDAC was about twofold higher than that of the
      mitochondrial VDAC, which could result either form higher labeling of the SR
      protein or from relatively higher amounts of VDAC/mg total protein in the SR
      membranes. [14C]Dicyclohexylcarbodiimide labeling of the SR, but not the
      mitochondrial VDAC, was biphasic with respect to time and concentration of
      [14C]dicyclohexylcarbodiimide. Partial digestion of [14C]dicyclohexylcarbodiimide
      labeled SR-VDAC with chymotrypsin yielded five proteolytic fragments which were
      recognized by the anti-VDAC Ig, and the dicyclohexylcarbodiimide-binding site was
      localized in the 19-kDa fragment. VDAC was purified from SR and mitochondrial
      membranes by spermine-agarose column. The interaction of dicyclohexylcarbodiimide
      with functional carboxyl residue(s) in the purified VDAC is demonstrated by
      recording its channel activity, following its reconstitution into planar lipid
      bilayer (PLB). Dicyclohexylcarbodiimide inhibited the channel activity in a
      voltage-dependent manner, requiring incubation with dicyclohexylcarbodiimide at
      high (negative or positive) potentials. Dicyclohexylcarbodiimide slowed down the
      transition from the high-conducting to a long-lived low-conducting states of the
      channel (approximately 20% of its maximal conductance), by stabilizing the
      intermediate states. Similar results were also obtained with purified
      reconstituted mitochondrial VDAC. Hydrophilic carboxyl reagents [[1-ethyl-3-(3
      dimethylamino)propyl] carbodiimide, N-ethyl-phenylisoxazolium-3'-sulfonate]
      neither modified the channel activity nor prevented [14C]dicyclohexylcarbodiimide
      labeling. These results indicate that dicyclohexylcarbodiimide interacts with a
      carboxyl group located in a hydrophobic region of the protein which is involved
      in the channel gating.

PMID- 9654060
TI  - Inhibition of growth and aggregation of calcium oxalate crystals in vitro--a
      comparison of four human proteins.
AB  - The aim of this study was to compare directly, in the absence of interfering
      contaminants, the inhibitory effects of Tamm-Horsfall glycoprotein (THG), human
      serum albumin (HSA), alpha1-microglobulin and prothrombin fragment 1 (PTF1) on
      calcium oxalate crystallization. These proteins have been detected in urinary
      calculi, and with the exception of THG in calcium oxalate crystals generated from
      undiluted human urine. THG was isolated from the urine of healthy men, while PTF1
      was purified from Prothrombinex-HT, a human blood concentrate; HSA and alpha1
      microglobulin were obtained from commercial sources. The effects of these
      proteins were determined, separately, at the same final concentration (32 nM) on
      calcium oxalate crystallization in a seeded, inorganic reaction system, using
      Coulter Counter and [14C]oxalate analysis. Analysis of [14C]oxalate data showed
      that THG, HSA and alpha1-microglobulin had no measurable effect on deposition of
      calcium oxalate. However, PTF1 significantly inhibited mineral deposition by
      19.6%. The average size of the particles precipitated was reduced from the
      control value of 8.6 microm to 7.3, 5.9, 5.6 and 4.0 microm in the presence of
      alpha1-microglobulin, HSA, THG and PTF1 respectively. These findings were
      confirmed by scanning electron microscopy, which also revealed that the smaller
      particles deposited in the presence of the proteins resulted from reduced crystal
      aggregation rather than a decrease in the size of the individual crystals. It was
      concluded that, on a molar basis, PTF1 is a more potent inhibitor of calcium
      oxalate crystal aggregation than THG, HSA and alpha1-microglobulin. Moreover,
      unlike those proteins it significantly inhibits the deposition of calcium
      oxalate. These findings have implications for the putative role of urinary
      proteins in the formation of calcium oxalate stones.

PMID- 9654061
TI  - The formate dehydrogenase-cytochrome c553 complex from Desulfovibrio vulgaris
      Hildenborough.
AB  - The electron transfer between formate dehydrogenase and cytochrome c553 from the
      anaerobic bacteria Desulfovibrio vulgaris Hildenborough has been investigated.
      Parameters of the electron transfer kinetics are reported. The ionic strength
      dependence of the complex formation has been evidenced. Two mutants of cytochrome
      c553 have been obtained using site-directed mutagenesis with the substitutions
      K62E and K62E,K63E. According to one-dimensional and two-dimensional NMR
      analysis, the two variants were found to have the same folding pattern as that of
      the wild-type cytochrome. The replacements of the lysine residues by acidic
      groups have important effects on the affinity between the two oxidoreduction
      partners. K62 and K63 are essential for recognition between the formate
      dehydrogenase and the cytochrome c553. Previous structural studies of cytochrome
      c553 have demonstrated the involvement of the polypeptide chain in the modulation
      of the particular low oxidoreduction potential of this cytochrome. The present
      study provides evidence that, during the evolution of cytochromes from the
      anaerobic metabolism to aerobic respiration and photosynthesis, the electrostatic
      distribution at the recognised encounter surface around the heme is highly
      conserved in all cytochromes.

PMID- 9654062
TI  - Pigment-binding properties of the recombinant photosystem II subunit CP26
      reconstituted in vitro.
AB  - CP26 is the most recently described antenna protein in higher plants which has
      been reported to be involved in xanthophyll-dependent regulation of the light
      harvesting function but is largely unknown due to the difficulties of
      purification. In this study we have overexpressed in Escherichia coli the Lhcb5
      gene product and reconstituted CP26 in vitro by refolding the recombinant protein
      in the presence of chlorophyll a, chlorophyll b and xanthophylls. The resulting
      pigment-protein complex is stable enough to be isolated by partially denaturing
      gel electrophoresis. Reconstitution and isolation conditions for CP26 are similar
      to those used for other chlorophyll a/b complexes like the major light-harvesting
      complex of photosystem II (LHCII) and CP29; however, CP26 differs with regard to
      its lower specificity in carotenoid binding. Most significantly, rather stable
      recombinant CP26 can be reconstituted containing violaxanthin as the only
      carotenoid. This enhanced plasticity with respect to carotenoid binding is
      consistent with CP26 being the major binding protein of violaxanthin involved in
      the xanthophyll cycle. The availability of recombinant CP26 opens the way to a
      better characterisation of this pigment-protein complex with regard to its
      biochemistry and its physiological functions.

PMID- 9654063
TI  - Oxygen exchange with water in heme-oxo intermediates during H2O2-driven oxygen
      incorporation in aromatic hydrocarbons catalyzed by microperoxidase-8.
AB  - The present paper describes the oxygen incorporation into naphthalene and
      anthracene by H2O2-driven microperoxidase-8, forming alpha-naphthol and
      anthraquinone, respectively. Microperoxidase-8 is a minienzyme containing a
      histidinyl-coordinated Fe3+-protoporphyrin IX cofactor covalently attached to an
      eight-amino-acid peptide. Additional experiments were performed to investigate
      whether the reaction mechanism involved is like that of peroxidase and/or
      cytochrome P-450. A reaction pathway like that of cytochrome P-450 implies oxygen
      transfer to the substrate from the as yet uncharacterized iron-oxo species formed
      in the reaction of the heine cofactor with H2O2. In contrast, a peroxidase-type
      reaction chemistry involves reaction pathways proceeding by initial one-electron
      oxidation of, or H-abstraction from, the substrate, followed by incorporation of
      oxygen from sources other than the iron-oxo species, i.e. from other than H2O2.
      The results of the present study exclude Fenton-type chemistry and prove that the
      minicatalyst is able to catalyze the oxygen incorporation by both peroxidase and
      cytochrome P-450 types of reaction pathways, while exchange occurs between the
      high-valency iron-oxo species and H2O. The mechanistic implications of this
      exchange for cytochrome P-450 are discussed.

PMID- 9654064
TI  - Kinetic analysis of integrin-dependent cell adhesion on vitronectin--the
      inhibitory potential of plasminogen activator inhibitor-1 and RGD peptides.
AB  - Distinct binding interactions between cell-surface receptors and extracellular
      matrix components are characteristic of multifunctional adhesion proteins such as
      vitronectin. The close proximity of binding sites for alpha(v)-integrins and
      plasminogen activator inhibitor-1 (PAI-1) on vitronectin may have consequences
      for cell adhesion and migration, or for the localized inhibition of plasminogen
      activators. In this study, the kinetics and reversibility of vitronectin
      dependent cell adhesion via alpha(v)-integrins was investigated using RGD
      peptides and PAI-1 as competitors. Active, but not latent or cleaved PAI-1, and
      RGD peptides were effective in preventing cell adhesion to vitronectin provided
      the inhibitor was present at the time of cell seeding. In a concentration
      dependent manner urokinase or thrombin abrogated the inhibitory effect of PAI-1.
      Following cell seeding onto a vitronectin substratum, delayed addition of RGD
      peptides or active PAI-1 (10-20 min post-seeding) resulted in the loss of their
      inhibitory potential. These data were supported by experiments in a purified
      system where delayed addition of active PAI-1 could no longer prevent vitronectin
      binding to immobilized alpha(v)beta3, while a cyclic RGD peptide gave some
      moderate inhibition. The apparent stabilization of vitronectin-integrin contacts
      was observed with immobilized native or multimeric vitronectin but not with the
      more rigid form of denatured, aggregated multimers. These results demonstrate
      that the cell adhesive properties of vitronectin depend on its conformational
      flexibility and can be tightly regulated in a spatio-temporal manner through
      direct competition of cellular integrins by soluble or matrix-bound factors such
      as PAI-1.

PMID- 9654065
TI  - Cloning, purification and characterisation of the lipase from Staphylococcus
      epidermidis--comparison of the substrate selectivity with those of other
      microbial lipases.
AB  - On the chromosome of Staphylococcus epidermidis RP62A the lipase gene (gehSE1) is
      immediately flanked by the icaAA'BC operon, which is involved in biofilm
      formation. Since lipase production might play a role in staphylococcal skin
      colonisation as well, we studied the biochemical properties of the staphylococcal
      lipases more closely. The DNA sequence and the deduced protein sequence revealed
      that gehSE1 is very similar to the lipase sequence of S. epidermidis strain 9.
      Like other staphylococcal lipases, gehSE1 is organised as a preproenzyme. The
      part of gehSE1 coding for the mature lipase was cloned and overexpressed as a
      fusion protein with an N-terminal histidine tag in Escherichia coli. The lipase
      was purified to homogeneity using a combination of precipitation techniques,
      metal-affinity chromatography and gel filtration. Biochemical characterisation
      showed that this lipase is closely related to the lipase from Staphylococcus
      aurelis NCTC8530. Both enzymes have a pH optimum around 6, are very stable at low
      pH, and need calcium as a cofactor for catalytic activity. The preferred
      substrates are small triacylglycerols, with a maximum activity toward
      tributyrylglycerol. Comparison of the substrate selectivity with those of other
      microbial lipases showed that phospholipids are generally poor substrates for
      lipases. An exception is the lipase from Staphylococcus hyicus, which prefers
      phospholipids as a substrate, distinguishing this staphylococcal lipase from
      other microbial lipases. These results are discussed in view of the
      structure/function relationships of staphylococcal lipases, and the possible
      involvement of these enzymes in biological processes such as skin colonisation
      and pathogenesis.

PMID- 9654066
TI  - Sulfhydryl reagent susceptibility in proteins with high sequence similarity-
      triosephosphate isomerase from Trypanosoma brucei, Trypanosoma cruzi and
      Leishmania mexicana.
AB  - The amino acid sequence of triosephosphate isomerase from Trypanosoma brucei,
      Trypanosoma cruzi, and Leishmania mexicana have an identity of 68%. Using the
      numbering system for the T. brucei enzyme, in their aligned sequences, the T.
      cruzi and leishmanial enzymes have cysteine residues at positions 14, 40, 117 and
      126. T. brucei triosephosphate isomerase has cysteine residues at positions 14,
      40 and 126, and a valine residue at position 117. Dithionitrobenzoic acid and
      methylmethane thiosulfonate inhibited the three enzymes, but T. cruzi
      triosephosphate isomerase was more than 100-fold more sensitive. The sensitivity
      of wild type triosephosphate isomerase from T. cruzi and T. brucei to the
      reagents was equal to that of the Cys117Val and Val117Cys mutant enzymes,
      respectively. Triosephosphate isomerases that have cysteine residues at positions
      40 and 126, but lack a cysteine residue at position 14 are insensitive to
      methylmethane thiosulfonate. Thus, sulfhydryl reagents act on Cys14. At
      stoichiometric concentrations, the reagents inhibited the three enzymes as a
      consequence of structural alterations as measured by binding of 8-anilino-1
      napthalenesulfonic acid to previously buried hydrophobic regions. However, the
      times for half-maximal alterations were 10 min, 15 hours and over 30 hours for T.
      cruzi, T. brucei and L. mexicana triosephosphate isomerase, respectively. The
      effect of pH on the action of the sulfhydryl reagents and molecular modeling
      showed no differences in the solvent accessibility of Cys14. As Cys14 forms part
      of the dimer interface, the data indicate that, in the three enzymes, barriers of
      different magnitude hinder the interaction between the sulfhydryl reagents and
      Cys14. The barrier is lower in T. cruzi triosephosphate isomerase which makes its
      dimer interface more susceptible for perturbation.

PMID- 9654067
TI  - Purification and characterization of dimethylamine:5-hydroxybenzimidazolyl
      cobamide methyltransferase from Methanosarcina barkeri Fusaro.
AB  - Dimethylamine:5-hydroxybenzimidazolylcobamide methyltransferase (DMA-MT) was
      purified from cells of Methanosarcina barkeri Fusaro grown on trimethylamine. In
      the presence of methylcobalamine:coenzyme M methyltransferase isoenzyme II
      [MT2(II)] the enzyme quite specifically catalyzed the stoichiometric conversion
      of dimethylamine (apparent Km = 0.45 mM) and 2-mercaptoethane-sulfonate (coenzyme
      M) to monomethylamine and methyl-coenzyme M. Monomethylamine was a competitive
      inhibitor of the reaction (Ki = 4.5 mM). The apparent molecular mass of DMA-MT
      was 100 kDa and the enzyme was found to be a dimer, composed of identical 50-kDa
      subunits. A corrinoid content of 0.9 +/- 0.1 mol B12/mol holoenzyme was
      calculated from HPLC analysis. The as-isolated methyltransferase was inactive,
      but it could be reductively reactivated. Activation required the presence of
      methyltransferase-activating protein, ATP and dimethylamine. Incubation with
      these compounds resulted in the methylation of the corrinoid prosthetic group.

PMID- 9654068
TI  - Methanol:coenzyme M methyltransferase from Methanosarcina barkeri--identification
      of the active-site histidine in the corrinoid-harboring subunit MtaC by site
      directed mutagenesis.
AB  - The enzyme system catalyzing the formation of methyl-coenzyme M from methanol and
      coenzyme M in Methanosarcina barkeri is composed of the three different
      polypeptides MtaA, MtaB and MtaC of which MtaC harbors a corrinoid prosthetic
      group. The heterologous expression of mtaA and mtaB in Escherichia coli has been
      described previously. We report here on the overproduction of the apoprotein of
      MtaC in E. coli, on its reconstitution to the active holoprotein with either
      cob(II)alamin or methyl-cob(III)alamin, and on the properties of the
      reconstituted corrinoid protein. Reconstituted MtaC was found to contain 1 mol
      bound cobamide/mol. EPR spectroscopic evidence is presented for a His residue as
      an axial ligand to Co2+ of the bound corrinoid. This active-site His was
      identified by site-directed mutagenesis as His136 in the MtaC sequence that
      contains four His residues. The reconstituted MtaC, in the cob(I)amide oxidation
      state, was methylated with methanol in the presence of MtaB and demethylated with
      coenzyme M in the presence of MtaA. In the presence of both MtaB and MtaA, methyl
      coenzyme M was formed from methanol and coenzyme M at specific rates comparable
      to those determined for the enzyme system purified from M. barkeri. M. barkeri
      contains an isoenzyme of MtaA designated MtbA. The isoenzyme reacted with MtaC
      with only 2.5% of the activity of MtaA.

PMID- 9654069
TI  - O-demethylase from Acetobacterium dehalogenans--substrate specificity and
      function of the participating proteins.
AB  - The ether-cleaving O-demethylase isolated from syringate-grown cells of
      Acetobacterium dehalogenans (formerly named strain MC) consists of four proteins,
      components A, B, C and D. The enzyme system converts only phenyl methyl ethers
      with a hydroxyl group in the ortho position to the methoxyl moiety. The presence
      of a carboxyl group in the aromatic compound was not required for O-demethylase
      reaction. Component B mediated the conversion of vanillate to 3,4
      dihydroxybenzoate in the presence of the Ti(III)-reduced corrinoid-containing
      component A. After addition of component D and tetrahydrofolate, methyl
      tetrahydrofolate was formed from vanillate in stoichiometric amounts.
      Titanium(III) citrate as a reductant could be replaced by H2, methyl viologen or
      ferredoxin, partially purified hydrogenase, purified component C obtained from A.
      dehalogenans, and ATP. From these findings, it was deduced that component B
      serves as vanillate:corrinoid protein methyltransferase (methyltransferase I)
      mediating the methyl transfer from vanillate to the reduced corrinoid protein
      component A. Component D functions as methylcorrinoid protein:tetrahydrofolate
      transferase (methyltransferase II). The role of component C is probably that of
      an activating protein reversing accidental oxidation of the protein-bound
      cob(I)alamin to cob(II)alamin in the presence of ATP and reducing equivalents
      supplied by the enzymatic oxidation of hydrogen.

PMID- 9654070
TI  - Kinetic mechanism of vanillyl-alcohol oxidase with short-chain 4-alkylphenols.
AB  - The kinetic mechanism of vanillyl-alcohol oxidase with 4-methylphenol, 4
      ethylphenol, 4-propylphenol and their C alpha-deuterated analogs has been studied
      at pH 7.5 and 25 degrees C. Conversion of 4-methylphenol is extremely slow (0.005
      s(-1)) while the enzyme is largely in the reduced form during turnover. 4
      Ethylphenol and 4-propylphenol are readily converted while the enzyme is mainly
      in the oxidized form during turnover. The deuterium kinetic isotope effect for
      overall catalysis ranges between 7-10 whereas the intrinsic deuterium kinetic
      isotope effect for flavin reduction ranges over 9-10. With all three 4
      alkylphenols, flavin reduction appeared to be a reversible process with the rate
      of reduction being in the same range as the rate for the reverse reaction. During
      the reductive half-reaction of vanillyl-alcohol oxidase with 4-ethylphenol and 4
      propylphenol, a transient intermediate is formed with an absorbance maximum at
      330 nm. This intermediate has been tentatively identified as the p-quinone
      methide of the aromatic substrate in complex with reduced enzyme. It is concluded
      that vanillyl-alcohol oxidase catalysis with 4-ethylphenol and 4-propylphenol
      favors an ordered sequential binding mechanism in which the rate of flavin
      reduction determines the turnover rate while the reduced enzyme-p-quinone methide
      binary complex rapidly reacts with dioxygen. During the reaction of vanillyl
      alcohol oxidase with 4-methylphenol, a fluorescent enzyme species is stabilized.
      Based on its spectal characteristics and crystallographic data [Mattevi, A.,
      Fraaije, M. W., Mozzarelli, A., Olivi, L., Coda, A. & van Berkel, W. J. H. (1997)
      Structure 5, 907-920], it is proposed that this species represents a covalent 5
      (4'-hydroxybenzyl)-FAD adduct. With 4-ethylphenol and 4-propylphenol, similar N5
      flavin adducts may be formed but their rate of formation is too slow to be of
      catalytic relevance.

PMID- 9654071
TI  - Structure and regulation of the bifunctional enzyme lysine-oxoglutarate reductase
      saccharopine dehydrogenase in maize.
AB  - The lysine-oxoglutarate reductase (LOR) domain of the bifunctional enzyme lysine
      oxoglutarate reductase-saccharopine dehydrogenase (LOR/SDH) from maize endosperm
      was shown to be activated by Ca2+, high salt concentration, organic solvents and
      Mg2+. The Ca2+-dependent enhancement of LOR activity was inhibited by the
      calmodulin antagonists N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W7)
      and calmidazolium. Limited proteolysis was used to assess the structure/function
      relationship of the enzyme. Digestion with elastase separated the bifunctional
      125-kDa polypeptide into two polypeptides of 65 kDa and 57 kDa, containing the
      functional domains of LOR and SDH, respectively. Proteolysis did not affect SDH
      activity, while LOR showed a time-dependent and protease-concentration-dependent
      inactivation followed by reactivation. Prolonged digestion or increasing amounts
      of elastase produced a complex pattern of limit polypeptides derived from
      additional cleavage sites within the 65-kDa (LOR) and 57-kDa (SDH) domains. The
      SDH-containing polypeptides inhibited the enzymatic activity of LOR-containing
      polypeptides. When separated from the SDH domain by limited proteolysis and ion
      exchange chromatography, the LOR domain retained its Ca2+ activation property,
      but was no longer activated by high salt concentrations. These results suggest
      that the LOR activity of the native enzyme is normally inhibited such that after
      modulation, the enzyme undergoes a conformational alteration to expose the
      catalytic domain for substrate binding.

PMID- 9654072
TI  - Structure and cross-reactivity of the O-specific polysaccharide of Proteus
      penneri strain 26, another neutral Proteus O-antigen containing 2-acetamido-2,6
      dideoxy-L-glucose (N-acetyl-L-quinovosamine).
AB  - A neutral O-specific polysaccharide obtained from the lipopolysaccharide of
      Proteus penneri strain 26 was studied using sugar analysis and 1H and 13C NMR
      spectroscopy, including two-dimensional NMR techniques. The following structure
      of the trisaccharide repeating unit was established: -->6)-alpha-D-GlcpNAc-(1-
      >3)-alpha-L-QuipNAc-(1-->3)-alpha-D-Glcp NAc-(1--> where L-QuiNAc is 2-acetamido
      2,6-dideoxy-L-glucose (N-acetyl-L-quinovosamine). Cross-reactivity of the Proteus
      penneri 26 anti-O serum with other strains of P. penneri isolated in Poland and
      USA and one strain of P. vulgaris is discussed.

PMID- 9654073
TI  - The 58-kDa microspherule protein (MSP58), a nucleolar protein, interacts with
      nucleolar protein p120.
AB  - Protein p120 is a proliferation-related nucleolar protein which is detectable
      early in the G1 phase of the cell cycle and peaks early in the S phase. Most
      human malignant tumors contain much higher levels of protein p120 than normal
      resting cells. To identify p120-associated protein(s), a yeast two-hybrid screen
      was carried out using protein p120 as the bait. Two positive clones encoded
      portions of a novel protein, designated microspherule protein 58 kDa (MSP58).
      MSP58 mRNA is 1.9 kb and encodes an approximately 58-kDa polypeptide of 462 amino
      acids as shown by Western blotting of HeLa nucleolar proteins. The mouse MSP58
      homolog has 97% amino acid similarity to human MSP58, but no MSP58 homolog was
      found in the yeast genome. The MSP58 N-terminal region contains serine-rich
      clusters and its C-terminal region has a coiled-coil domain. In insect Sf9 cells,
      recombinant p120 and MSP58 proteins associated with each other, confirming the
      results of the yeast two-hybrid assay. Deletion mutations revealed that the
      binding of MSP58 to p120 required a previously unrecognized coiled-coil domain
      within the N-terminal region of p120 and the C-terminal region of MSP58 protein.
      Immunofluorescence indicated that the MSP58 protein is localized in
      microspherules in the nucleolus. Anti-MSP58 Ig labeled nucleolar 'caps' when HeLa
      cells were treated with actinomycin D. When the MSP58 protein was overexpressed
      in COS-7 cells, the nucleolus became irregularly enlarged, which suggests that
      MSP58 may affect the size and shape of the nucleolus.

PMID- 9654074
TI  - Reductive metabolism of the hypoxia marker pimonidazole is regulated by oxygen
      tension independent of the pyridine nucleotide redox state.
AB  - 2-Nitroimidazoles, such as pimonidazole, are reduced in cells with low oxygen
      tension and are, therefore, used as hypoxia markers. However, the effect of the
      pyridine nucleotide redox state on pimonidazole reduction is not known.
      Therefore, livers from fed or fasted rats were perfused with oxygen-saturated
      buffer containing pimonidazole (400 microM) in the presence and absence of an
      inhibitor of the mitochondrial respiratory chain, potassium cyanide; these
      treatments were used to modulate the mitochondrial and cytosolic pyridine
      nucleotide redox states. Pimonidazole-induced increases in oxygen uptake over
      basal values were as follows: fed, 15.1 +/- 2.4; fasted, 4.2 +/- 0.8; fed + KCN,
      32.1 +/- 0.9; fasted + KCN, 0.2 +/- 0.2 micromol x g(-1) x h(-1). However, if
      NADPH was added in excess, microsomal oxygen uptake due to oxidative metabolism
      of pimonidazole was independent of treatment. These results indicate that
      pimonidazole-stimulated O2 uptake, due predominantly to N-oxidation and
      glucuronidation, is dependent on the NADPH redox state. In contrast, reduced
      pimonidazole adducts, detected immunochemically, accumulated in pericentral
      regions in liver. Increasing the NADH redox state by inhibiting the mitochondrial
      respiratory chain with KCN decreased protein-bound pimonidazole adducts.
      Concomitantly, the average O2 tension of the liver was increased at least 30%.
      However, KCN had no effect on total pimonidazole adducts detected by ELISA,
      although both cytosolic (lactate/pyruvate) and mitochondrial (3
      hydroxybutyrate/acetoacetate) NADH redox states were elevated by at least a
      factor of eight. These results indicate that, unlike oxidative metabolism, the
      pyridine nucleotide redox state does not determine the rate of reductive
      metabolism of pimonidazole. Instead, the cellular oxygen tension regulates this
      process. Therefore, even in cases where the supply of reducing equivalents is
      increased (e.g., ethanol metabolism), accumulation of the reduced bound product
      of pimonidazole is oxygen dependent in liver.

PMID- 9654075
TI  - Engineering, expression and biochemical characterization of the hemoglobin domain
      of a Erwinia chrysanthemi flavohemoprotein.
AB  - An artificial hemoglobin-like domain has been constructed by engineering the gene
      coding for the multi-domain flavohemoprotein from the bacterium Erwinia
      chrysanthemi. This domain was designed by molecular modelling, cloned and over
      expressed in Escherichia coli. The holo-protein was obtained in large quantities
      after extraction from inclusion bodies and refolding in presence of alkaline
      hemin. The purified 140-residue domain was studied and characterized to gain new
      insights into the biochemical function of the recombinant domain and the
      biological role of this new flavohemoprotein. The structural and functional
      features of this domain in solution were studied using far-ultraviolet circular
      dichroism, resonance Raman, proton-NMR spectroscopy, flash laser photolysis and
      molecular modelling. The recombinant domain is shown to be folded properly and
      active. This hemoglobin-like domain is able to bind oxygen and carbon monoxide
      with very high affinity. It exhibits a rapid auto-oxidation which may explain its
      tight association with a flavin containing reductase domain. A functional model
      of this hemoglobin is discussed and compared with the X-ray structures of other
      hemoproteins.

PMID- 9654076
TI  - Photophysical properties of porphyrin planar aggregates in liposomes.
AB  - This paper describes studies of some photophysical properties of non-covalent
      planar aggregates of hematoporphyrin and protoporphyrin. This porphyrin species
      has been recently discovered and can be generated in lipid bilayers such as
      liposomes and inner mitochondrial membranes. The relative weight of this species
      in different media, as compared to porphyrin monomers and stacked aggregates, has
      been deduced by fluorescence decay studies. In contrast with what is observed for
      stacked aggregates, promotion of planar suprastructures can occur both in aqueous
      and lipid environments. The spectroscopic properties are very similar to those of
      the corresponding monomers, in particular as regards the shape of the absorption
      and emission spectra. The fluorescence decay times are generally higher than
      those of the monomers, and depend on the medium in which the planar aggregates
      are formed. The photooxidation properties of porphyrin planar aggregates, as
      revealed by oxygen consumption and histidine photodegradation upon irradiation at
      365 nm, were compared to those of the monomers. The extent of the photooxidation
      process is nearly 20-30% higher in planar aggregates than in the monomers. In
      contrast, it is well known that cofacial aggregates are photochemically inert and
      only monomeric species of porphyrin are efficient photosensitizers. The
      biological relevance of these findings is discussed.

PMID- 9654077
TI  - Induction of necrosis by zinc in prostate carcinoma cells and identification of
      proteins increased in association with this induction.
AB  - Zinc exhibits inhibitory effects on apoptosis, and a deficiency in this metal
      generally causes this type of cell death to occur. In the present study, we found
      that exposure to zinc results in necrosis of prostate carcinoma cells. When zinc
      acetate was added to LNCaP or PC-3 cells in monolayer culture, they began to
      detach from the culture dishes, and viability was lost after 4-8 h. Most of the
      cell death was found to be due to necrosis as determined by double staining with
      fluorescein-isothiocyanate-labeled annexin V and ethidium bromide, and by
      detection of hypodiploid cells. Associated with the induction of necrosis was an
      increase in low molecular-mass proteins, identified by HPLC analysis to be
      thymosin beta10, parathymosin and GAGE in LNCaP cells, and thymosin beta4,
      parathymosin and metallothionein in PC-3. The time course of the increase of
      thymosin beta10 in LNCaP cells and thymosin beta4 in PC-3 cells was consistent
      with that of appearance of cell detachment and dead cells. These results indicate
      that zinc can induce necrosis and suggest that production of proteins including
      beta-thymosins is involved in induction of processes leading to cell detachment.

PMID- 9654078
TI  - Oxygen-regulated erythropoietin gene expression is dependent on a CpG methylation
      free hypoxia-inducible factor-1 DNA-binding site.
AB  - The hypoxia-inducible factor-1 (HIF-1) is a transcriptional activator involved in
      the expression of oxygen-regulated genes such as that for erythropoietin.
      Following exposure to low oxygen partial pressure (hypoxia), HIF-1 binds to an
      hypoxia-response element located 3' to the erythropoietin gene and confers
      activation of erythropoietin expression. The conserved core HIF-1 binding site
      (HBS) of the erythropoietin 3' enhancer (CGTG) contains a CpG dinucleotide known
      to be a potential target of cytosine methylation. We found that methylation of
      the HBS abolishes HIF-1 DNA binding as well as hypoxic reporter gene activation,
      suggesting that a methylation-free HBS is mandatory for HIF-1 function. The in
      vivo methylation pattern of the erythropoietin 3' HBS in various human cell lines
      and mouse organs was assessed by genomic Southern blotting using a methylation
      sensitive restriction enzyme. Whereas this site was essentially methylation-free
      in the erythropoietin-producing cell line Hep3B, a direct correlation between
      erythropoietin protein expression and the degree of erythropoietin 3' HBS
      methylation was found in different HepG2 sublines. However, the finding that this
      site is partially methylation-free in human cell lines and mouse tissues that do
      not express erythropoietin suggests that there might be a general selective
      pressure to keep this site methylation-free, independent of erythropoietin
      expression.

PMID- 9654079
TI  - Transcriptional regulation of the non-specific cross-reacting antigen gene, a
      member of the carcinoembryonic antigen gene family up-regulated in colorectal
      carcinomas.
AB  - Human non-specific cross-reacting antigen (NCA), a close relative of the tumor
      marker human carcinoembryonic antigen (CEA), is also an in vitro homotypic
      intercellular adhesion molecule capable of inhibiting differentiation when
      expressed ectopically by myoblasts. Moreover, NCA appears to be overexpressed at
      the transcriptional level to a greater extent and more frequently in colorectal
      carcinomas than CEA. This study examines the transcriptional control mechanisms
      responsible for orchestrating NCA expression. The region within 284 bp upstream
      of the translational start site of the NCA gene was found to be capable of
      directing high levels of expression in functional promoter assays. Footprinting
      experiments identified three cis-acting elements and mobility-shift assays
      revealed that the first of these elements is bound by the upstream stimulating
      factors USF1 and USF2 while the other two are bound by the stimulatory proteins
      Sp1 and Sp3. No cis-acting elements corresponding to CEA footprint FP4 or the
      silencer CEA FP5 were detected in the NCA promoter, which may contribute to the
      differential expression of NCA versus CEA in tumorigenesis.

PMID- 9654080
TI  - DNA-binding properties of the tandem HMG boxes of high-mobility-group protein 1
      (HMG1).
AB  - High-mobility-group protein 1 (HMG1) is a conserved chromosomal protein with two
      homologous DNA-binding HMG-box domains, A and B, linked by a short basic region
      to an acidic carboxy-terminal tail. NMR spectroscopy on the free didomain (AB)
      shows that the two HMG boxes do not interact. The didomain has a higher affinity
      for all DNA substrates tested than single HMG-box domains and has a significantly
      higher ability to distort DNA by bending and supercoiling. The interaction of the
      didomain with DNA is stabilized by the presence of the basic region
      (approximately 20 residues, 9 of which are Lys) that links the second HMG box to
      the acidic tail in intact HMG1; this may be, at least in part, why this region
      also enhances supercoiling of relaxed circular DNA by the didomain and
      circularization of short DNA fragments (in the presence of ligase). Competition
      assays suggest significantly different structure-specific preferences of single
      and tandem HMG boxes for four-way junction and supercoiled plasmid DNA. Binding
      to supercoiled DNA appears to be promoted by protein oligomerization, which is
      pronounced for the didomains. Electron microscopy suggests that the oligomers are
      globular aggregates, associated with DNA looping. One box versus two (or several)
      is likely to be an important determinant of the properties of (non-sequence
      specific) HMG-box proteins.

PMID- 9654081
TI  - Cloning and characterization of a cDNA coding for Astacus embryonic astacin, a
      member of the astacin family of metalloproteases from the crayfish Astacus
      astacus.
AB  - The astacin family of zinc endopeptidases was named after the digestive enzyme
      astacin isolated from the crayfish Astacus astacus. Employing a reverse
      transcription/PCR strategy with degenerate oligonucleotide primers specific for
      two signature seqences of the astacin family, we have isolated a 1602-bp cDNA
      from embryos of developing A. astacus eggs, which was designated Astacus
      embryonic astacin (AEA). This cDNA was found to code for an astacin-like protease
      domain which accounts for the N-terminal half of the predicted protein. The C
      terminal half mainly consists of two complement subcomponent C1r/C1s/embryonic
      sea urchin protein Uegf/bone morphogenetic protein 1 (CUB) domains. The
      metalloprotease domain displays an amino acid sequence identity of 42% with
      astacin. A higher sequence similarity was found to astacin family members that
      act as hatching enzymes in different species, e.g. chorioallantoic membrane
      protein 1 (CAM-1; from quail) and Xenopus hatching enzyme (formerly UVS.2), both
      of which show 54% identity, and high and low choriolytic enzymes (HCE and LCE)
      from the teleost Oryzias latipes (52% and 48% identity, respectively). A
      relationship to astacin-like hatching enzymes is further supported by a
      phylogenetic analysis of the protease domains. Expression of AEA mRNA in
      developing embryos was found to be restricted to unhatched juveniles (larvae)
      during the last 8 days before hatching. AEA transcripts could not be detected in
      various tissues of adult animals or in eggs and embryos from an earlier
      developmental stage. AEA expression starts about 8 days prior to hatching,
      followed by a strong (18-fold) induction with a maximum at day 4 before hatching.
      Newly hatched juveniles were found not to express the AEA mRNA.

PMID- 9654082
TI  - Molecular cloning, expression and characterization of an Ascaris inhibitor for
      pepsin and cathepsin E.
AB  - Molecular cloning of a cDNA for a pepsin inhibitor in the round worm, Ascaris
      suum, was achieved. The ORF was found to encode a 20-residue potential signal
      peptide and a 149-residue inhibitor moiety. Northern analysis showed the mRNA for
      the inhibitor to be expressed in the body wall and not in the viscera. To obtain
      the active inhibitor, we constructed a yeast expression vector, pYES2API,
      containing the inducible galactosidase promoter and a DNA fragment encoding a
      fusion protein of the yeast alpha-factor leader and the Ascaris pepsin inhibitor.
      The active inhibitor was secreted in the culture medium, the yield being
      approximately 3 mg x l(-1) x day(-1), and purified by a two-step procedure that
      included HPLC. The inhibitor inactivated pepsin A and cathepsin E almost
      completely at amounts equimolar with the enzymes, but was 100-fold less effective
      against pepsin C and did not act on cathepsin D and renin. Ki values for the
      inhibition of pepsin A and cathepsin E were in the nanomolar range below pH 5.
      Since the inhibitor activity was lost by modification of specific Lys residues,
      including Lys110, an electrostatic interaction between these Lys residues and
      Asp/Glu residues of pepsin A or cathepsin E was thought to be essential for the
      inhibition.

PMID- 9654083
TI  - Growth-blocking peptide expressed in the insect nervous system--cloning and
      functional characterization.
AB  - Growth-blocking peptide (GBP) is an insect biogenic peptide that retards larval
      growth and, consequently, delays the onset of pupation of lepidopteran larvae.
      Transcription of the GBP gene has been proven to be regulated in a tissue
      dependent manner by an approximately 0.8-kb mRNA transcript in fat body and 2.5
      kb transcript in the brain central nervous system (CNS) [Hayakawa, Y., Ohnishi,
      A., Yamanaka, A., Izumi, S. & Tomino, S. (1995) FEBS Lett. 367, 185-189]. The GBP
      cDNA in the brain CNS was isolated, sequenced and found to be almost identical
      with that in the fat body, except that it encodes a long 5'-untranslated region
      (approximately 1.1 kb), thus indicating that the brain CNS is synthesized as a
      polyprotein precursor and released through posttranslational processing in the
      same manner as that predicted in the fat body. Sequence analyses of the genomic
      GBP gene fragments demonstrated that the 5'-untranslated region contains an
      intron encoding a sequence element, TGATAA, which has been reported to be
      important for expression in the insect larval fat body, suggesting that this
      element contributes to a tissue-specific expression of the shorter GBP mRNA in
      fat body. Ribonuclease protection assays showed that parasitization by a
      parasitic wasp elevated the expression of GBP mRNA in brain CNS. The
      parasitization-induced increase of GBP precursor and GBP concentrations was also
      demonstrated in brain CNS. Brain CNS dopamine was increased eightfold by
      incubating the tissue with GBP for 8 h through the elevation of dopa
      decarboxylase activity by a transcriptional enhancement perhaps due to GBP
      induced increase of cytoplasmic Ca2+ concentration. Dopamine elevation reduced in
      vitro incorporation of methionine into proteins synthesized in brain CNS.

PMID- 9654084
TI  - A bifunctional hybrid molecule of the amino-terminal fragment of urokinase and
      domain II of bikunin efficiently inhibits tumor cell invasion and metastasis.
AB  - Urinary trypsin inhibitor (UTI) inhibits efficiently tumor cell invasion and the
      formation of metastasis. The anti-metastatic effect is dependent on the COOH
      terminal domain II of UTI [UTI-(78-136)-peptide]. To develop a molecule that
      binds with high affinity to the urokinase (uPA) receptor (uPAR) on tumor cell
      surfaces, a bifunctional hybrid molecule [uPA-(1-134)-UTI-(78-136)] consisting of
      the uPAR-binding NH2-terminal fragment [UTI-(78-136)-peptide] of uPA at the NH2
      terminus of UTI-(78-136)-peptide was produced in Escherichia coli by genetic
      engineering. The purified hybrid protein inhibited trypsin and plasmin 2-3-fold
      less effectively than UTI-(78-136)-peptide and was found to bind to human tumor
      cells via uPAR, which was confirmed by cell binding and competition experiments.
      Using a modified Boyden chamber and an artificial basement membrane, Matrigel, it
      was found that the hybrid protein is very effective at inhibiting invasion by
      uPAR-expressing human tumor cells. Sensitivities of tumor cells towards the anti
      invasive effect of uPA-(1-134)-UTI-(78-136) correlated with the density of uPAR
      on human tumor cells. Furthermore, in the spontaneous metastasis model, the
      hybrid protein inhibited the formation of lung and/or lymphatic metastasis by
      human ovarian carcinoma and choriocarcinoma cells. The hybrid protein was much
      more effective than uPA-(1-134)-peptide, UTI-(78-136)-peptide, or UTI. We
      conclude that this approach extends the possibility of applying recombinant
      protein for therapeutic use in inhibition of human tumor cell metastasis.

PMID- 9654085
TI  - Phosphatidylinositol 4-kinases.
AB  - Polyphosphoinositides are involved in many signal transduction pathways in
      eukaryotic cells. The first committed step is catalysed by phosphatidylinositol 4
      kinase leading to the formation of phosphatidylinositol 4-phosphate. In the last
      four years, ten cDNA molecules have been cloned which code isoforms of
      phosphatidylinositol 4-kinase; some of which are highly related.
      Characteristically, they contain a C-terminal catalytic domain which is similar
      to that of (poly)phosphoinositide 3-kinases and to that of more distantly related
      lipid/protein kinases. Alignment has characterised cDNAs from Chaenorabditis,
      Dictyostelium and Schizostaphyloccus pombe as those of phosphatidylinositol 4
      kinases also. All these lipid kinases are related to the superfamily of protein
      kinases. Several amino acids are highly conserved in catalytic domains of lipid
      and protein kinases. Employing the catalytic subunit of the cAMP-dependent
      protein kinase as template, these residues can be assigned functionally. On the
      basis of the alignment, a phylogenetic tree of the superfamily of
      phosphatidylinositol kinases has been constructed. Three families, the
      phosphatidylinositol 4-kinases, phosphoinositide 3-kinases, and the
      phosphatidylinositol related lipid/protein kinases, can be recognised. Each
      family comprises two subfamilies. The involvement of the phosphatidylinositol 4
      kinases in signal transduction processes is summarised and a new hypothesis for
      the function of their isoforms in polyphosphoinositide signalling is presented.
      The involvement of phosphatidylinositol 4-kinases in formation of lipid-protein
      interactions with cytoskeleton proteins and the metabolism of
      polyphosphoinositide in the nucleus is discussed.

PMID- 9654086
TI  - Monitoring of RNA polymerase-DNA UP element interaction by a fluorescent probe
      conjugated to alpha subunit.
AB  - The carboxy-terminal domain (CTD) of Escherichia coli RNA polymerase alpha
      subunit was specifically modified by a reporter label, fluorescein mercuric
      acetate (FMMA), conjugated to Cys269 on the surface of UP element recognition
      helix. The modified enzyme was used to investigate RNA polymerase interaction
      with different promoters, either with or without an UP element. In a single-round
      transcription assay, the activity of modified RNA polymerase was found to
      decrease as measured with rrnBP1, trpP and lacP2 promoters but not with many
      other promoters including mutant rrnBP1 without the UP element, supporting the
      idea that Cys269 or the domain including Cys269 is involved in UP element
      recognition. Both trpP and lacP2 have sequence similarity to the rrnBP1 UP
      element. The chemical modification of RNA polymerase, however, did not affect an
      apparent equilibrium dissociation constant with rrnBP1, as measured by gel
      retardation assays, indicating that the DNA-binding ability is retained even
      after FMMA conjugation. Interaction with the rrnBP1 UP element led to substantial
      alterations in the spectral parameters of the reporter label, which are different
      from those induced by complex formation with promoters without UP elements. A
      pronounced spectral blue shift suggests that the labeled surface of alphaCTD
      closely approaches the charged UP DNA helix. These observations imply that the
      fluorescent labeling at Cys269 can be used as a good tool for monitoring the
      presence or absence of an UP element in a given promoter. Spectral parameters of
      the label displayed the spectral blue shift when the modified RNA polymerase
      interacted with trpP, supporting the prediction that this promoter carries an
      rrnBP1-type UP element.

PMID- 9654087
TI  - Tyrosine phosphorylation of the muscle-specific kinase is exclusively induced by
      acetylcholine receptor-aggregating agrin fragments.
AB  - During formation of the neuromuscular junction, the basal membrane protein agrin
      initiates the aggregation of acetylcholine receptors (AChR) on the surface of
      myotubes. A muscle-specific kinase (MuSK) becomes phosphorylated upon incubation
      with agrin, although it does not bind to agrin on its own. Utilizing MuSK
      specific antibodies, we demonstrate that the ability of different splicing
      variants and truncation fragments of agrin to trigger MuSK phosphorylation and
      AChR aggregation are correlated. Only agrin forms which are potent inducers of
      AChR-clustering are able to trigger the phosphorylation of MuSK. Picomolar
      concentrations of agrin are already sufficient to induce MuSK phosphorylation.
      Similar amounts are necessary for the aggregation of AChRs as well as their
      phosphorylation on a tyrosine residue. The complete overlap of specificities for
      MuSK phosphorylation and AChR aggregation suggests that only binding of agrin to
      a MuSK-containing receptor complex is responsible for the initiation of AChR
      aggregation. In contrast, interactions of agrin with binding proteins on the
      muscle surface harbouring different specificities such as alpha-dystroglycan do
      not seem to be necessary for this process.

PMID- 9654088
TI  - Different forms of the mRNA encoding the heat-shock transcription factor are
      expressed during the life cycle of the parasitic helminth Schistosoma mansoni.
AB  - Several cDNAs and a gene encoding the heat-shock transcription factor (HSF) of
      schistosome were cloned, and multiple forms of the mRNA were found at different
      developmental stages of the parasite. The encoded protein contained a DNA-binding
      domain with expected sequence identity (39-58%) to other HSF molecules, and two
      leucine zipper motifs (LZ123 and LZ4) involved in the oligomerization of HSF.
      Adult worms express three isoforms of HSF mRNA generated by alternative splicing
      inside the coding region that contains in-frame splice signals. Introns are not
      involved in the process since the deleted segments (36 bp or 45 bp) are not
      flanked by any intron in the gene. Structural variations generated by alternative
      splicing (insertion of 3 amino acids or 15 amino acids) are continual with LZ4
      and added hydrophobic residues are in register with the hydrophobic heptad
      repeats of LZ4. Structural diversity at the C-terminus of LZ4 may affect the
      strength of LZ4 interaction with the oligomerization domain (LZ123) and thus
      modulate the DNA-binding activity of HSF. The conservation of this mechanism in
      mouse and schistosome may reflect evolutionary pressure to generate multiple HSF
      species exhibiting functional diversity and capable of responding to different
      stress signals and physiological signals. Adult worms express HSF mRNA of 2.5 kb,
      in agreement with the size of the cDNA, while cercariae (developmental stage
      preceding adult worm) show multiple bands in the range 2.5-3 kb. Available data
      indicate that the HSF mRNAs of cercariae are inactive. We propose that these mRNA
      species are generated by an alternative splicing that incorporates introns, which
      inactivate the mRNA by the insertion of termination codons and/or by shifting of
      the reading frame. Parasite HSF protein produced in bacteria showed DNA sequence
      recognition similar to that of HSF in parasite extracts, i.e. the recombinant HSF
      reacted better with a variant heat-shock element (HSE; one base change in the
      third NGAAN pentamer of the ideal HSE consensus sequence) than with the ideal
      HSE. The size of the HSF gene is 12 kb and it is composed of ten exons and nine
      introns. Excluding the introns, the gene and cDNA show 100% sequence identity. A
      plant HSF gene contains only a single intron, which matches with the position of
      intron I2 of schistosome. That the position of this intron is conserved in remote
      species is indicative of an important function during evolution of the HSF gene.

PMID- 9654089
TI  - Molecular cloning and characterization of mouse caspase-8.
AB  - Fas (APO-1/CD95) is a transmembrane receptor protein which induces apoptosis upon
      activation. In apoptosis triggered by Fas, a subset of cysteine proteases
      designated caspases is activated, playing a central role as effector molecules.
      Among these caspases, human caspase-8 (FLICE/MACH/Mch5) has been isolated and
      shown to be indispensable for Fas-mediated apoptotic signaling. In this study, we
      isolated the mouse homologue to human caspase-8 from a BaF3 cell cDNA library.
      This molecule conserved the death effector domain (DED) and protease domain as
      detected in human caspase-8, and was capable of inducing apoptosis in KB and Rat
      1 cells when overexpressed. Expression of caspase-8 was detected in the various
      tissues of adult mouse and in embryos at 9.5 days and 17.5 days of development by
      Northern-blot analysis. Further, we isolated a chromosomal gene for caspase-8
      from a mouse genomic library and analyzed the genomic structure of the isolated
      gene. This gene consisted of eight exons and seven introns spanning about 26 kb
      in the coding region.

PMID- 9654090
TI  - Studies on the conformational changes in the bacterial cell wall biosynthetic
      enzyme UDP-N-acetylglucosamine enolpyruvyltransferase (MurA).
AB  - The enzyme UDP-N-acetylglucosamine (UDP-GlcNAc) enolpyruvyltransferase (MurA),
      the target of the antibiotic fosfomycin, was investigated by small-angle X-ray
      scattering (SAXS) and fluorescence spectroscopy to detect conformational changes
      that had been proposed on the basis of the crystal structure of unliganded and
      liganded MurA. The SAXS data indicate that binding of UDP-GlcNAc to free enzyme
      results in substantial conformational changes, which can be interpreted as the
      transition from an open to a closed form. Fosfomycin did not affect the structure
      of free enzyme or sugar-nucleotide-bound MurA. Phosphoenolpyruvate (pyruvate-P)
      appeared to induce a structural change upon addition to free enzyme, which
      differed from that observed upon binding of UDP-GlcNAc. Fluorescence experiments
      were performed using the hydrophobic fluorescence probe 8-anilino-1-naphthalene
      sulfonate (ANS). The fluorescence quenching of MurA/ANS solutions upon addition
      of UDP-GlcNAc or pyruvate-P was concentration dependent in a saturating manner,
      yielding apparent dissociation constants of K(d(UDP-GlCNAc)) = 59 microM and
      K(d(pyruvate-P)) = 240 microM. The results suggest that binding of substrates
      does not exclusively follow an ordered mechanism with UDP-GlcNAc binding first,
      although binding of UDP-GlcNAc to free enzyme is preferred and possibly
      influenced by pyruvate-P. The reaction thus appears to follow an induced-fit
      mechanism, in which the binding site for fosfomycin, and presumably also for
      pyruvate-P, is created by the interaction of free enzyme with the sugar
      nucleotide. The methods described here provide a tool for the characterization of
      site-directed mutants of MurA and the interaction of this enzyme with potential
      inhibitors.

PMID- 9654091
TI  - Effect of single mutations on the structural dynamics of a DNA repair enzyme, the
      Escherichia coli formamidopyrimidine-DNA glycosylase--a fluorescence study using
      tryptophan residues as reporter groups.
AB  - The effects on the structure dynamics of the Escherichia coli wild-type
      formamidopyrimidine-DNA glycosylase (Fpg) protein of the single mutations Lys57-
      >Gly (FpgK57G), Pro2-->Gly (FpgP2G) and Pro2-->Glu (FpgP2E) were studied by
      fluorescence techniques, namely: lifetime measurements and acrylamide quenching
      of the fluorescence of Trp residues. The fluorescence decays of Fpg and its
      mutant forms were analysed by the maximum-entropy method and lifetime
      distributions in the range 200 ps to 9 ns were obtained. The lifetime
      distribution profiles of FpgK57G, FpgP2G and FpgP2E are different from that of
      wild-type Fpg. Both dynamic and static quenching by acrylamide were observed for
      all the proteins. At 20 degrees C, the bimolecular collisional quenching rate
      constant of the FpgP2E fluorescence by acrylamide was only 0.8 M(-1) s(-1) as
      compared to about 1.4 M(-1) s(-1) for the three other proteins. At 6 degrees C,
      all the spectroscopic properties of these four proteins are about the same. The
      analysis of experimental data demonstrates that all three mutations induce a
      structural reorganization of the Fpg protein. However, only the P2E mutation lead
      to a reduced accessibility of some Trp residues to acrylamide quenching. It is
      concluded that the single P2E replacement induces a conformational change leading
      to a more rigid globular structure as opposed to the wild type and K57G and P2G
      mutations. The influence of the single mutations on the enzyme activities of the
      Fpg protein is discussed.

PMID- 9654092
TI  - Downstream targets of urokinase-type plasminogen-activator-mediated signal
      transduction.
AB  - We have investigated cellular signalling events induced by urokinase-type
      plasminogen activator (uPA) independent of its proteolytic activity. Treatment of
      the human fibrosarcoma cell line HT 1080 with diisopropylphosphorofluoridate
      inactivated uPA (Dip-F-uPA) triggers a cascade of intracellular signals which are
      mediated by the specific cell surface receptor for uPA (uPAR). We have found that
      anti-uPAR Ig precipitate the src-type protein tyrosine kinases fyn, hck and lck,
      which belong to a family of structurally and functionally related effectors
      participating in signalling from antigen and cytokine receptors. Of the three
      uPAR-associated kinases, only hck is activated by uPA, whereas no changes in the
      activities of either fyn or lck could be detected by an in vitro immune complex
      kinase assay. We identified p38 and extracellular-signal-regulated kinase 2 from
      the mitogen-activated protein kinase family as downstream components of a set of
      consecutive signalling molecules which teleologically alter the program of gene
      expression. Exposure of cells to uPA results in a significant increase in c-fos
      mRNA that is partially due to an elevated rate of gene transcription. Presumably,
      the activation of the c-fos gene leads to the subsequent formation of the
      transcription factor activator protein-1 (AP-1), since accumulation of c-fos mRNA
      is followed by induction of target genes sensitive to AP-1 such as plasminogen
      activator inhibitor type 2 (PAI-2). These results provide new insights into
      proteolysis-independent cytokine-like effects of uPA.

PMID- 9654093
TI  - Expression of fatty-acid-binding proteins in cells involved in lung-specific
      lipid metabolism.
AB  - Members of the fatty-acid-binding protein (FABP) family are thought to play an
      important role in fatty acid transport within the cytosol and thus to be involved
      in lipid metabolism. As previous data on the occurrence of distinct FABP types in
      total lung are contradictory, we determined the expression of FABP types in three
      isolated cell types of rat lung, which are characterised by active lipid
      metabolism. Alveolar type-II cells synthesise, store and secrete pulmonary
      surfactant, a phospholipid-rich surface-tension-lowering agent, whereas lung
      fibroblasts, localised adjacent to the alveolar type-II cells, are assumed to
      provide neutral lipid substrate to alveolar type-II cells around birth, and
      alveolar macrophages are known to degrade complex lipids. Initial screening by
      reverse transcriptase PCR revealed the occurrence of heart (H-), epidermal (E-)
      and liver FABP in rat lung, the latter being not detectable in the three cell
      types studied. Cells were analysed by northern and western blotting, then
      quantitatively by sandwich ELISA, for which recombinant rat E-FABP was prepared.
      E-FABP mRNA was found in all three cell types, and E-FABP was detected in the
      following amounts: 240.9 +/- 19.0 ng/mg cytosolic protein in alveolar type-II
      cells; 172.3 +/- 0.7 ng/mg protein for lung fibroblasts; and 36.9 +/- 3.5 ng/mg
      protein for alveolar macrophages. This indicates a basic function of E-FABP in
      cellular lipid metabolism. In contrast, H-FABP probably is involved in the
      metabolism of neutral lipids because H-FABP mRNA was found only in lung
      fibroblasts with a corresponding protein level of 315.5 +/- 6.9 ng/mg. Small
      amounts of H-FABP protein were present in alveolar type-II cells and alveolar
      macrophages.

PMID- 9654094
TI  - The reductase RedA2 of the multi-component dioxin dioxygenase system of
      Sphingomonas sp. RW1 is related to class-I cytochrome P450-type reductases.
AB  - The first step in the oxidation of the diaryl ethers dibenzo-p-dioxin and
      dibenzofuran by the bacterium Sphingomonas sp. RW1 is carried out by an atypical
      multi-component ring hydroxylating dioxygenase. This heteromeric enzyme requires
      the participation of a flavoprotein, reductase A2, and an iron-sulfur protein,
      Fdx1, to mediate the transfer of electrons from NADH to the dioxygenase for
      oxygen activation [Bunz, P. V. & Cook, A. M. (1993) J. Bacteriol. 175, 6467
      6475]. From the type of ferredoxin (Fd) and flavoprotein, this complex is
      presumed to belong to the class-IIA dioxygenase system which has not been
      genetically analysed so far. The gene encoding the flavoprotein was identified by
      screening a genomic library constructed in pLAFR3 with a probe generated by PCR
      amplification. The nucleotide sequence of a 2.0-kb DNA fragment encompassing the
      reductase gene, redA2, was determined. The specified protein shares 37-40%
      identity with class-I cytochrome P450 reductases and 27-35% identity with
      reductases acting with class-IIB dioxygenases. An FAD-binding amino acid
      consensus sequence, as well as an NADH-binding site were detected by analogy
      beginning at residues 10 and 153, respectively. The redA2 gene is not linked to
      the dioxin dioxygenase cistrons. The rare start codon, GTG, of the reductase was
      changed to ATG and the modified gene hyperexpressed in Escherichia coli using the
      strong T7 polymerase promoter. The recombinant reductase was purified to
      homogeneity with an approximate yield of 3.3 mg/g wet mass cells. Flavin analysis
      confirmed the presence of 1 FAD/mol protein. The Km values for NADH and Fdx1 are
      22 (+/- 3) microM and 3.7 (+/- 0.4) microM, respectively.

PMID- 9654095
TI  - Molecular cloning and characterization of tomato cDNAs encoding glutathione
      peroxidase-like proteins.
AB  - In Lycopersicon esculentum, two cDNAs encoding glutathione peroxidase (GPX)-like
      proteins were isolated, sequenced and characterized as putative phospholipid
      hydroperoxide:glutathione peroxidases. After mechanical stimulation (rubbing) of
      the plant, each GPX tomato gene was found to behave differently in terms of
      inducibility and tissue distribution. The accumulation of GPX transcripts
      suggests that reactive oxygen species are involved in the plant response to a
      mechanical stress.

PMID- 9654096
TI  - Bactericidal activity of Lys49 and Asp49 myotoxic phospholipases A2 from Bothrops
      asper snake venom--synthetic Lys49 myotoxin II-(115-129)-peptide identifies its
      bactericidal region.
AB  - Mammalian group-II phospholipases A2 (PLA2) of inflammatory fluids display
      bactericidal properties, which are dependent on their enzymatic activity. This
      study shows that myotoxins II (Lys49) and III (Asp49), two group-II PLA2 isoforms
      from the venom of Bothrops asper, are lethal to a broad spectrum of bacteria.
      Since the catalytically inactive Lys49 myotoxin II isoform has similar
      bactericidal effects to its catalytically active Asp49 counterpart, a
      bactericidal mechanism that is independent of an intrinsic PLA2 activity is
      demonstrated. Moreover, a synthetic 13-residue peptide of myotoxin II, comprising
      residues 115-129 (common numbering system) near the C-terminal loop, reproduced
      the bactericidal effect of the intact protein. Following exposure to the peptide
      or the protein, accelerated uptake of the hydrophobic probe N-phenyl-N
      naphthylamine was observed in susceptible but not in resistant bacteria,
      indicating that the lethal effect was initiated on the bacterial membrane. The
      outer membrane, isolated lipopolysaccharide (LPS), and lipid A of susceptible
      bacteria showed higher binding to the myotoxin II-(115-129)-peptide than the
      corresponding moieties of resistant strains. Bacterial LPS chimeras indicated
      that LPS is a relevant target for myotoxin II-(115-129)-peptide. When
      heterologous LPS of the resistant strain was present in the context of
      susceptible bacteria, the chimera became resistant, and vice versa. Myotoxin II
      represents a group-II PLA2 with a direct bactericidal effect that is independent
      of an intrinsic enzymatic activity, but adscribed to the presence of a short
      cluster of basic/hydrophobic amino acids near its C-terminal loop.

PMID- 9654097
TI  - Thermodynamic stability of two variants of xylanase (Xys1) from Streptomyces
      halstedii JM8.
AB  - In a continuation of our earlier study [Ruiz-Arribas, A., Santamaria, R.I.,
      Zhadan, G. G., Villar, E. & Shnyrov, V. L. (1994) Differential scanning
      calorimetric study of the thermal stability of xylanase from Streptomyces
      halstedii JM8, Biochemistry 33, 13787-13791], we used high-sensitivity
      differential scanning microcalorimetry, intrinsic tryptophan fluorescence and far
      ultraviolet circular dichroism to study the effect of regional sequence
      differences on the thermodynamic stability of xylanase (Xys1) from Streptomyces
      halstedii JM8 (1,4-beta-D-xylanohydrolase, EC 3.2.1.8). Thermal transitions were
      measured for original xylanase (Xys1S) and two variants. Thermal denaturation of
      all the xylanases studied revealed two structural domains, each of which, despite
      its partial irreversibility, follows a two-state thermal unfolding process under
      our experimental conditions. Both variants were found to exhibit slightly
      decreased stability, possessing the same activity as the original. The unfolding
      parameters for each domain of both variants, unlike the situation with wild-type
      xylanase (see our previous report), fit some correlations obtained for the most
      compact globular proteins. The values of enthalpy and entropy of
      unfolding/residue at 383 K were found to be inversely proportional to residual,
      well-regulated structures in unfolded states.

PMID- 9654098
TI  - The initial kinetics of hydrolysis by cellobiohydrolases I and II is consistent
      with a cellulose surface-erosion model.
AB  - Introduction of a novel method for the quantification of the cellobiose released
      made it possible to follow the initial stage of hydrolysis of bacterial
      microcrystalline cellulose (BMCC) by cellobiohydrolases 1,4-beta-D-glucan
      cellobiohydrolase I (CBH I) and 1,4-beta-D-glucan-cellobiohydrolase II (CBH II)
      from Trichoderma reesei. A drastic retardation of the rate of the hydrolysis was
      observed already at a very low degree of conversion. Earlier-suggested
      retardation factors, such as product inhibition by cellobiose or enzyme
      inactivation, could be discounted as primary causes for the pattern. A model
      including steric hindrance by non-productive binding and erosion of the cellulose
      surface during the processive action of exoenzymes was proposed to describe the
      rate retardation observed. Simultaneous action of CBH I and CBH II on cellulose
      was not a prerequisite for synergy between them.

PMID- 9654099
TI  - Effect of mutations of residue 340 in the large subunit polypeptide of Rubisco
      from Anacystis nidulans.
AB  - Residues 338-342 at the C-terminal end of loop 6 in the large subunit beta/alpha
      barrel structure of Rubisco influence specificity towards CO2 and O2. In
      Anacystis nidulans Rubisco, replacement of alanine 340 by tyrosine or histidine
      increased the specificity factor by 12-13%, accompanied by a 25-33% fall in Vc,
      the rate of carboxylation, while replacement by asparagine increased the
      specificity factor by 9% and Vc by 19%. Other mutations did not significantly
      alter specificity. Alanine 340 does not interact directly with the bisphosphate
      substrate, thus replacing it with other residues must have indirect effects on
      the specificity factor and rate of carboxylation.

PMID- 9654100
TI  - Pyrrole-2-carboxylate decarboxylase from Bacillus megaterium PYR2910, an organic
      acid-requiring enzyme.
AB  - Inducible pyrrole-2-carboxylate decarboxylase, which catalyzes the
      decarboxylation of pyrrole-2-carboxylate to pyrrole and CO2 in stoichiometric
      amounts, was purified from Bacillus megaterium PYR2910. The purity of the enzyme
      was shown by SDS/PAGE and gel-permeation HLPC. The enzyme has a molecular mass of
      approximately 98 kDa and consists of two identical subunits. It is highly
      specific for pyrrole-2-carboxylate, and also catalyzes the reverse reaction, the
      carboxylation of pyrrole. A unique feature of this enzyme is its requirement of
      an organic acid, such as acetate, propionate, butyrate or pimelate. A possible
      catalytic mechanism including a cofactor function of organic acid is discussed.

PMID- 9654101
TI  - Structural characterisation of N-linked and O-linked oligosaccharides derived
      from interferon-alpha2b and interferon-alpha14c produced by Sendai-virus-induced
      human peripheral blood leukocytes.
AB  - We have previously isolated and partially characterised the components of a
      highly purified interferon-alpha (IFN-alpha) preparation produced by Sendai-virus
      induced human peripheral blood leukocytes. Nine IFN-alpha species were
      identified, and two of these were found to be glycosylated [Nyman, T. A., Tolo,
      H., Parkkinen, J. & Kalkkinen, N. (1998) Identification of nine interferon-alpha
      subtypes produced by Sendai-virus-induced human peripheral blood leukocytes,
      Biochem. J. 329, 295-302]. Here, we isolated the N-linked oligosaccharides of IFN
      alpha14c and the O-linked chains of IFN-alpha2b, and the glycans were
      characterised by electrospray tandem mass spectrometry and by specific
      glycosidase digestions monitored by matrix-assisted laser desorption ionisation
      time of flight mass spectrometry. The IFN-alpha14c N-glycans were shown to
      exhibit core-fucosylated biantennary glycans, with about 10% carrying an
      additional alpha1,3-linked fucose unit at the antennae. The IFN-alpha2b was shown
      to carry about 50% core type-1 disialyltetrasaccharides, 30% core type-1
      monosialyltrisaccharides and 20% core type-2 monosialylpentasaccharides.

PMID- 9654102
TI  - Mutant analysis reveals an alternative pathway for N-linked glycosylation in
      Drosophila melanogaster.
AB  - The mas-1 gene of Drosophila melanogaster encodes Golgi mannosidase I (MAS-1),
      and flies homozygous for small deletions of the gene are viable. They show but
      few abnormalities and those have a low penetrance [Kerscher, S., Albert, S.,
      Wucherpfennig, D., Heisenberg, M. & Schneuwly, S. (1995) Dev. Biol. 168, 613
      626]. Here we sequence the N-linked oligosaccharides associated with a reporter
      protein, and with membrane proteins prepared from wild type and MAS-1 null
      organisms. The results show that the null organisms synthesise the same range of
      oligosaccharides as wild type, albeit with different ratios. There is an
      accumulation of the Man8GlcNAc2 which is one of the substrates for the MAS-1
      enzyme. This supports the suggestion of Kerscher et al. that the lack of severe
      phenotypic disturbances in the null organisms is due to the presence of an
      alternative pathway(s), but it also shows that this alternative pathway(s) does
      not entirely compensate for the normal pathway.

PMID- 9654103
TI  - Oligosaccharides derived by endo-beta-galactosidase digestion of bovine corneal
      keratan sulphate--characterisation of tetrasaccharides with incomplete sulphation
      and containing unsulphated N-acetylglucosamine residues.
AB  - Bovine corneal keratan sulphate has been fragmented using the enzyme endo-beta)
      galactosidase and 1H-NMR chemical shift data are reported for five newly isolated
      tetrasaccharides which derived from the repeat region. They have the structures:
      GlcNAc(beta1-3)Gal(beta1-4)GlcNAc6S(beta1-3)Gal-ol, GlcNAc6S(beta1-3)Gal(beta1
      4)GlcNAc(beta1-3)Gal-ol, GlcNAc(beta1-3)Gal6S(beta1-4)GlcNAc6S(beta1-3)Gal-ol,
      GlcNAc6S(beta1-3)Gal6S(beta1-4)GlcNAc(beta1-3)Gal-ol, and GlcNAc6S(beta1
      3)Gal(beta1-4)GlcNAc6S(beta1-3)Gal-ol. Structures for two trisaccharides formed
      by a peeling reaction are also given. These are GlcNAc(beta1-3)Gal6S(beta1
      4)GlcNAc-ol and GlcNAc6S(beta1-3)Gal(beta1-4)GlcNAc6S-ol where GlcNAc6S-ol
      represents N-acetylglucosaminitol 6-O-sulphate. Characterisation of such
      structures and their spectral assignments will be of considerable value for the
      studies of both selectin ligands and undersulphated keratan sulphates such as
      those occurring on cell surfaces and in brain tissue.

PMID- 9654104
TI  - Structural analysis of the phase-variable lipooligosaccharide from Haemophilus
      somnus strain 738.
AB  - The structure of the phase variable lipooligosaccharide (LOS) from Haemophilus
      somnus strain 738 was elucidated. The LOS was subjected to a variety of
      degradative procedures. The structures of the purified products were established
      by monosaccharide and methylation analyses, NMR spectroscopy and mass
      spectrometry. The following structures for the two major components were
      determined on the basis of the combined data from these experiments. [structure
      in text]. In the structures Kdo is 3-deoxy-D-manno-octulosonic acid, PEtn is
      phosphoethanolamine, PCho is phosphocholine, Hep is L-glycero-D-manno-heptose,
      and the remaining glucose units have the D configuration. The elucidation of
      these structures has increased our understanding of the relationship between the
      phase-variable LOS and the pathogenic potential of this organism.

PMID- 9654105
TI  - Rules for the addition of O-linked N-acetylglucosamine to secreted proteins in
      Dictyostelium discoideum--in vivo studies on glycosylation of mucin MUC1 and MUC2
      repeats.
AB  - One class of O-glycosylation in the simple eukaryote Dictyostelium discoideum
      involves the addition of a single N-acetylglucosamine residue to Ser and Thr
      residues on secreted or membrane-bound proteins at an early stage of development.
      A previously developed in vivo approach for the identification of acceptor sites
      for O-glycosylation was used to further characterise the specificity of the UDP
      GlcNAc :polypeptide N-acetylglucosaminyltransferase(s). Glutathione S-transferase
      fusion proteins were constructed to express and secrete the mucin peptide repeat
      for MUC1 (PDT1RPAPGS1T2APPAHGVT3S2A) and a MUC2-like peptide
      (PT1T2T3PIT4T5T6T7T8T9VT10PT11PT12PT13GT14QT15), respectively (superscript
      numbers indicate residues with the potential to be glycosylated). Monosaccharide
      analysis, electrospray-ionisation mass spectrometry and protein sequencing showed
      that the modification is a single N-acetylglucosamine attached to certain Thr
      residues. The MUC1 repeat was glycosylated on T2 and T3 and there were no
      modifications on T1 or on S1 and S2. The MUC2 glycopeptide was glycosylated on
      T1, T3, T5, T7, T9, T10, T11, T12, T13 and T14. Our results show that the D.
      discoideum glycosylation apparatus incorporates GlcNAc residues into peptide
      sequences similar to those reported for the addition of GalNAc residues in
      mammalian tissues. The anomeric linkage of the GlcNAc residues to the polypeptide
      chain was shown to be in alpha configuration as determined by NMR studies.

PMID- 9654106
TI  - Several weak signals in the cytosolic and transmembrane domains of the
      interleukin-2-receptor beta chain allow for its efficient endocytosis.
AB  - Plasma membrane receptors are retrieved continually from the cell surface by
      endocytosis and transported to intracellular organelles. They are internalized at
      various rates depending on their ability to interact with endocytic structures of
      the plasma membrane. The interleukin-2-receptor beta chain is endocytosed
      constitutively and efficiently. Here we show that different motifs in its
      cytosolic tail promote entry in an additive way, each of them acting as a weak
      internalization signal. The transmembrane domain of beta also participates in
      endocytosis. In conclusion, several weak endocytic determinants can be
      responsible for the rapid internalization of a membrane protein.

PMID- 9654107
TI  - In vitro schedule-dependent interaction between paclitaxel and SN-38 (the active
      metabolite of irinotecan) in human carcinoma cell lines.
AB  - Paclitaxel and irinotecan are important new anticancer agents. The combination of
      these two agents has been considered for use against a variety of advanced solid
      tumors. Since the schedule-dependent effects of this combination may be crucial
      to its use, we studied the interaction of paclitaxel and SN-38 (the active
      metabolite of irinotecan) in various schedules in four human cancer cell lines in
      culture. Cell growth inhibition after 5 days was determined using an MTT assay.
      The effects of drug combinations at the IC80 level were analyzed by the
      isobologram method. Simultaneous exposure to paclitaxel and SN-38 for 24 h
      produced antagonistic (subadditive and protective) effects in the human lung
      cancer cell line A549, the breast cancer cell line MCF7, and the colon cancer
      cell line WiDr, and produced additive effects in the ovarian cancer cell line
      PA1. Sequential exposure to paclitaxel for 24 h followed by SN-38 for 24 h, and
      the reverse sequence, produced additive effects in all four cell lines. These
      findings suggest that sequential administration, not simultaneous administration,
      may be the appropriate schedule for the therapeutic combination of paclitaxel and
      irinotecan. Continued preclinical and clinical studies should provide further
      insights and assist in determining the optimal schedule for this combination in
      clinical use.

PMID- 9654108
TI  - Clinical pharmacokinetics of intravenous treosulfan in patients with advanced
      solid tumors.
AB  - Treosulfan (L-threitol- 1,4-bis-methanesulfonate, Ovastat) is a prodrug of a
      bifunctional alkylating agent with activity in ovarian carcinoma and other solid
      tumors. For a clinical and pharmacology study, patients with advanced,
      refractory, or resistant solid tumors were treated with a single-dose intravenous
      30-min infusion of 8 or 10 g/m2 treosulfan. A sensitive method for the
      determination of treosulfan in plasma and urine by reverse-phase high-performance
      liquid chromatography was developed. A total of 14 plasma and urine treosulfan
      pharmacokinetics determinations were analyzed in the 8-g/m2 group and 7 were
      analyzed in the 10-g/m2 group, the maximum tolerated dose for this group of
      pretreated patients. The terminal half-life of treosulfan was in the range of 1.8
      h. AUC and Cmax values were significantly (P < 0.01) higher in the 10-g/m2 group
      (AUC 708+/-168 versus 977+/-182 microg ml(-1) h, Cmax 465+/-98 versus 597+/-94
      microg/ml). The mean urinary excretion of the parent compound was about 25% of
      the total dose delivered over 48 h (range 5-49%), and about 20% was excreted
      during the first 6 h after administration. Currently, a clinical phase I
      pharmacokinetics and dose-escalation trial with autologous blood stem-cell
      support has been started at 20 g/m2 treosulfan using a 2-h infusion protocol.

PMID- 9654109
TI  - Molecular characterization of human acute leukemia cell line resistant to ZD9331,
      a non-polyglutamatable thymidylate synthase inhibitor.
AB  - ZD9331 is a non-polyglutamatable, potent quinazoline antifolate inhibitor of
      thymidylate synthase (TS). In an effort to clarify the exact mechanism of
      resistance to this novel TS inhibitor, we examined the molecular alterations in
      its target enzyme TS, the transport protein (reduced folate carrier, RFC), and
      folylpolyglutamate synthetase (FPGS) in a human acute lymphoblastic leukemia cell
      line, MOLT-3, made resistant to ZD9331. A 310-fold resistant subline was
      established after 6 months exposure to the drug at concentrations up to 7 microM,
      and was designated MOLT-3/ ZD9331. MOLT-3/ZD9331 showed crossresistance to CB3717
      (4.8-fold), raltitrexed (63-fold) and methotrexate (MTX) (120-fold), but retained
      sensitivity to trimetrexate (0.88-fold). The resistant cells demonstrated
      impaired initial cellular uptake and low accumulation of [3H]MTX in accordance
      with a decreased expression of RFC1, suggesting the downregulation of RFC.
      However, Southern blot analysis demonstrated no change in gene copy number nor
      gross rearrangement of RFC1 in the resistant cells. In addition, MOLT-3/ZD9331
      showed amplification of the TS gene with a concomitantly increased level in the
      gene expression. In contrast, the expression of FPGS did not alter. These results
      demonstrate that continuous exposure of the cells to ZD9331 leads not only to a
      decreased expression of RFC1 but also to TS gene amplification and
      overexpression. The resistant mechanisms are likely to be regulated both at a
      genetic and a transcriptional level for different resistance phenotypes in the
      ZD9331-resistant MOLT-3 cells.

PMID- 9654110
TI  - Phase I and pharmacokinetic study of D-limonene in patients with advanced cancer.
      Cancer Research Campaign Phase I/II Clinical Trials Committee.
AB  - PURPOSE: D-Limonene is a natural monoterpene with pronounced chemotherapeutic
      activity and minimal toxicity in preclinical studies. A phase I clinical trial to
      assess toxicity, the maximum tolerated dose (MTD) and pharmacokinetics in
      patients with advanced cancer was followed by a limited phase II evaluation in
      breast cancer. METHODS: A group of 32 patients with refractory solid tumors
      completed 99 courses of D-limonene 0.5 to 12 g/m2 per day administered orally in
      21-day cycles. Pharmacokinetics were analyzed by liquid chromatography-mass
      spectrometry. Ten additional breast cancer patients received 15 cycles of D
      limonene at 8 g/m2 per day. Intratumoral monoterpene levels were measured in two
      patients. RESULTS: The MTD was 8 g/m2 per day; nausea, vomiting and diarrhea were
      dose limiting. One partial response in a breast cancer patient on 8 g/m2 per day
      was maintained for 11 months; three patients with colorectal carcinoma had
      prolonged stable disease. There were no responses in the phase II study. Peak
      plasma concentration (Cmax) for D-limonene ranged from 10.8+/-6.7 to 20.5+/-11.2
      microM. Predominant circulating metabolites were perillic acid (Cmax 20.7+/-13.2
      to 71+/-29.3 microM), dihydroperillic acid (Cmax 16.6+/-7.9 to 28.1+/-3.1
      microM), limonene-1,2-diol (Cmax 10.1+/-8 to 20.7+/-8.6 microM), uroterpenol
      (Cmax 14.3+/-1.5 to 45.1+/-1.8 microM), and an isomer of perillic acid. Both
      isomers of perillic acid, and cis and trans isomers of dihydroperillic acid were
      in urine hydrolysates. Intratumoral levels of D-limonene and uroterpenol exceeded
      the corresponding plasma levels. Other metabolites were trace constituents in
      tissue. CONCLUSIONS: D-Limonene is well tolerated in cancer patients at doses
      which may have clinical activity. The favorable toxicity profile supports further
      clinical evaluation.

PMID- 9654112
TI  - Phase I study of E7010.
AB  - E7010 is a novel sulfonamide which was discovered using slow-growing colon 38
      carcinoma cells as a screening model. E7010 exhibits a broad spectrum of
      antitumor activity against human tumor xenografts. The mechanism of action is by
      arresting the progression of cells in M phase of the cell cycle by inhibiting
      tubulin polymerization. The objective of this phase I study was to determine the
      maximum allowable dose (MAD), toxicity, and pharmacokinetics of single or 5-day
      repeated doses of E7010. In the single-dose study, E7010 was administered orally
      to 16 patients at doses ranging from 80 to 480 mg/m2. The dose-limiting toxicity
      was peripheral neuropathy at a dose of 480 mg/m2. Hematological and
      gastrointestinal toxicities were mild. In the 5-day repeated-dose study, 41
      patients were given E7010 at doses ranging from 30 to 240 mg/m2 per day. The dose
      limiting toxicities were peripheral neuropathy and intestinal paralysis.
      Gastrointestinal toxicity was dose-dependent but not severe. Hematological
      toxicity was not dose-dependent. Pharmacokinetic analysis in the single-dose
      study showed a rapid increase in the plasma levels of the drug after
      administration, followed by disappearance with a t1/2 of 4.4-16.6 h. The
      variation in area under the plasma concentration-time curve (AUC) between the
      patients was small and increased in a dose-dependent manner. Total drug recovery
      in urine 72 h after administration was 77.8+/-11.4%, indicating that E7010 has
      favorable absorption and elimination profiles. The changes in the plasma levels
      of E7010 on day 5 in the 5-day repeated-dose study were almost the same as those
      on day 1, indicating that the drug did not accumulate. In the single-dose study,
      spinal cord metastasis exhibited a 74% reduction in a patient with uterine
      sarcoma and a minor response (MR) was observed in a pulmonary adenocarcinoma
      patient. In the 5-day repeated-dose study decreases in the tumor markers
      carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC) were
      observed in a patient with stomach cancer and in a patient with recurrent uterine
      cervical carcinoma, respectively. The recommended phase II doses are 320 mg/m2
      for a single-dose study and 200 mg/m2 per day for a 5-day repeated-dose study.
      Since the activity of E7010 is time-dependent, i.e. a certain concentration of
      E7010 is required for more than 12 h to suppress the growth of P388 leukemia
      cells, it is recommended that subsequent phase I/II studies be conducted using a
      divided dose schedule in order to maintain the blood level of E7010.

PMID- 9654111
TI  - Increased 9-aminocamptothecin dose requirements in patients on anticonvulsants.
      NABTT CNS Consortium. The New Approaches to Brain Tumor Therapy.
AB  - BACKGROUND: High grade astrocytomas remain uniformly fatal despite aggressive
      surgery and radiotherapy. As existing chemotherapeutic agents are of limited
      benefit, clinical trials are underway to screen new drugs, such as 9
      aminocamptothecin (9-AC), for activity in high grade astrocytomas. PURPOSE: This
      study was designed to estimate the efficacy of 9-AC in patients with newly
      diagnosed glioblastoma multiforme and recurrent high grade astrocytomas. The
      planned dose of 9-AC for this trial was 850 microg/m2 per 24 h as a 72-h
      continuous intravenous infusion every 2 weeks. This was the maximum tolerated
      dose (MTD) on this schedule in multiple phase I studies in patients with systemic
      malignancies. However, we found this dose subtherapeutic in our patient
      population. As a result, the purpose of the study was altered to determine the
      MTD. METHODS: A group of 32 patients were studied using 850 microg/m2 per 24 h
      with a provision to escalate to 1000 microg/m2 per 24 h if the first three cycles
      of 9-AC were without significant hematologic toxicity. Once it was determined
      that myelosuppression did not occur in patients on anticonvulsants, dose
      escalations were initiated using the continual reassessment method. Dose
      escalations were conducted independently in newly diagnosed and recurrent
      patients and in those taking and not taking hepatic enzyme-inducing
      anticonvulsants. Pharmacologic studies were conducted during the first cycle of 9
      AC. Toxicity was determined using the NCI common toxicity criteria and efficacy
      was assessed using serial volumetric brain scans. RESULTS: 9-AC was administered
      to 59 patients, 31 with newly diagnosed glioblastoma multiforme and 28 with
      recurrent high grade astrocytomas. No grade III-IV myelosuppression was noted in
      the 29 patients (128 cycles) on phenytoin, carbamazepine, phenobarbital, and/ or
      valproic acid who received 850 microg/m2 per 24 h. In contrast, two of three
      patients (five cycles) who were not taking anticonvulsants developed grade IV
      myelosuppression. Steady-state total 9-AC plasma levels were lower in patients on
      anticonvulsants (median 25.3 nM) than in patients who were not taking
      anticonvulsants (median 76.5 nM). Dose escalations performed in 27 additional
      patients determined the MTD in patients taking anticonvulsants to be 1776
      microg/m2 per 24 h for patients with newly diagnosed tumors and 1611 microg/m2
      per 24 h for patients with recurrent disease. CONCLUSIONS: We describe a new and
      unexpected drug interaction between 9-AC and anticonvulsants. This is similar to
      recent findings with paclitaxel, and suggests that higher than "usual" doses of
      some chemotherapeutic agents are required in patients on anticonvulsants.
      Prospectively defined dose escalations and pharmacologic studies are essential
      for the careful evaluation of new chemotherapeutic agents in patients with brain
      tumors.

PMID- 9654113
TI  - Time dependency of hematopoietic growth factor coupled to chronotoxicity of
      carboplatin.
AB  - A growing body of data suggests that cancer therapy may be improved and toxicity
      reduced by administration of antineoplastic agents and cytokines at carefully
      selected times of the day. The time-dependent effects of each of the drugs have
      been documented, but not their mutual time dependencies. In the present studies
      we sought to determine the best time for granulocyte colony-stimulating factor (G
      CSF) administration after carboplatin treatment. Carboplatin was injected in
      different groups of ICR mice at four different circadian stages for 5 consecutive
      days. Mice were synchronized with an alternation of 12 h of light (from 6:00 a.m.
      to 6:00 p.m.) and 12 h of darkness. After the last injection, peripheral WBCs of
      three mice from each group were counted every 4 h over a 24-h period. Bone marrow
      toxicity was estimated with the mean 24-h WBC count. The most severe leukopenia
      occurred in the group injected at 3:00 p.m. - 9 h after light onset. The second
      set of experiments evaluated the time-dependent effect of G-CSF when singly
      injected or given after carboplatin injections for 5 days only at 3:00 p.m. G-CSF
      was injected into various groups on days 8 and 9 at the same four different
      circadian stages. On the 10th day after the first injection, peripheral WBCs of
      three mice from each group were counted every 4 h over a 24-h period. Time
      dependent effects were observed when G-CSF was injected as a single agent. When G
      CSF was given at various times to the group with the most severe carboplatin
      induced leukopenia, peripheral WBC count recovery was monitored at all injection
      times; it reached its highest level (exceeding even that of the control) when G
      CSF was injected at 3:00 a.m. Dosing times of both chemotherapy and growth factor
      are relevant for optimization of carboplatin's hematologic tolerability.

PMID- 9654114
TI  - Phase I study of oral JM216 given twice daily.
AB  - JM216 [bis-acetato-ammine-dichloro-cyclohexylamine-platinum(IV)] is an oral
      platinum complex that is currently in phase II trials in ovarian cancer and lung
      cancer on a daily-times-5 schedule. This trial examined an alternative schedule
      of two doses given 12 h apart, which may be better tolerated by patients. A total
      of 19 patients were given 50 cycles of treatment at doses ranging from 150 to 350
      mg/m2 b.i.d. The study was stopped before the MTD was reached due to non-linear
      pharmacokinetics. Toxicity was similar to that encountered in previous phase I
      studies, with nausea, vomiting and diarrhoea being seen at all dose levels,
      although this was generally mild and short-lived, and grade 3 and 4
      myelosuppression being seen at dose levels ranging from 250 to 350 mg/m2. There
      was no nephro-, oto-, or neurotoxicity, but one patient had an allergic reaction
      at 300 mg/m2 on the fifth and sixth cycles. No response was seen, but two
      patients with mesothelioma had stable disease and received six cycles. There was
      considerable interpatient variability in plasma pharmacokinetics at all dose
      levels. There was no relationship between dose and AUC (dose 1 and dose 2) or
      Cmax after dose 1. In a limited number of patients the first dose was given in
      the morning rather than in the evening, apparently resulting in lower AUC, Cmax
      and Tmax values at the 250-mg/m2 dose level, but this was not seen in one patient
      at 300 mg/m2. This study confirms that the pharmacokinetics of JM216 is non
      linear and highly variable due to saturable absorption and that the daily times 5
      schedule is the optimal schedule for further phase II trials.

PMID- 9654115
TI  - Analytical and biological inequivalence of two commercial formulations of the
      antitumor agent bleomycin.
AB  - Bleomycin is an antitumor agent which is a mixture of glycopeptides containing at
      least 55-75% bleomycin A2 and 25-32% bleomycin B2 fractional composition. Two
      bleomycin formulations, bleomycin sulfate, USP (Blenoxane, Bristol-Myers Squibb
      Oncology, Princeton, N.J.) and bleomycin HCI (Tianjin Hebei Pharmaceutical,
      Tianjin, China) were compared analytically and biologically. Reverse-phase high
      performance liquid chromatography (HPLC) analyses using the USP methodology
      showed that Blenoxane contained primarily (69%) bleomycin A2 and 29.3% bleomycin
      B2. In contrast, Tianjin-supplied bleomycin HCI contained 97% bleomycin A5
      fraction. In vitro tumor cell growth inhibition assays showed equivalent activity
      in human OVCAR-3 ovarian cancer cells and slightly greater potency in murine L
      1210 leukemia cells for the Tianjin formulation. In C57/B1 mice bearing B-16
      melanoma tumors, Tianjin-supplied bleomycin produced slightly greater tumor
      growth inhibition at the expense of greater drug-induced lethality at higher dose
      levels. These studies show there are significant differences in two international
      bleomycin formulations. These compositional differences lead to altered biologic
      effects.

PMID- 9654116
TI  - Evaluation of the linearity of docetaxel pharmacokinetics.
AB  - The taxanes, paclitaxel and docetaxel, have favorable response rates in patients
      with breast, gynecologic, and lung cancers and have demonstrated activity against
      a variety of malignancies. In human trials, paclitaxel pharmacokinetics are
      nonlinear and are best fit by a three-compartment model with nonlinear
      distribution into the second compartment as well as nonlinear elimination. This
      finding is important for patients receiving paclitaxel at high doses or as a
      short infusion, as it results in disproportionately high peak concentrations and
      delayed elimination. The presence of nonlinear processes in docetaxel
      pharmacokinetics has not previously been examined. Therefore, plasma
      concentration data obtained from 53 patients receiving docetaxel at 55-115 mg/m2
      over 1-24 h as part of phase I studies were modeled using the nonlinear three
      compartment model found most suitable for paclitaxel and the results were
      compared with those obtained using the linear version. Docetaxel disposition was
      best described by the three-compartment nonlinear model in 28 of 53 data sets
      (53%). However, the difference in curve fit observed between the two models was
      modest (did not improve Akaike criteria) and unlikely to be of relevance. This
      study suggests that nonlinear processes in docetaxel pharmacokinetics may exist,
      but, unlike the case of paclitaxel, they are not likely to have a significant
      impact at the dose and administration schedule used in routine clinical practice
      (60-100 mg/m2 given over 1 h by infusion). The presence of nonlinear docetaxel
      pharmacokinetics at doses above 115 mg/m2 will have to be determined in case of
      further dose escalation.

PMID- 9654117
TI  - Renal toxicity of the anticancer drug fostriecin.
AB  - PURPOSE: Fostriecin is an inhibitor of topoisomerase II catalytic activity. In a
      phase I trial we observed renal toxicity, documented as a rise in serum
      creatinine, which was reversible and non-dose-limiting. The purpose of this study
      was a detailed analysis of this toxicity. METHODS: A total of 20 patients
      received fostriecin as a 1-h i.v. infusion daily x 5 at doses ranging from 2 to
      20 mg/m2 per day. Serum creatinine determination and urinalysis were performed
      daily during drug administration. Renal hemodynamics were measured by means of
      clearance studies using 125I-iothalamate and (131)I-hippuran in eight patients at
      doses of > or =4 mg/m2 per day at baseline, on day 3 or 4 during the first
      course, and 3 weeks after the second course. RESULTS: The rise in serum
      creatinine was maximal after one to two doses despite continued administration.
      This increase showed no correlation with the dose level at fostriecin doses of >
      or =4 mg/m2 per day. Urinary beta2-microglobulin concentrations increased 150
      fold (median), which is compatible with impaired tubular reabsorption. The median
      change in the glomerular filtration rate (GFR) was -36% (range -28% to -44%),
      that in effective renal plasma flow (ERPF) was -23% (range -11% to -36%), and the
      filtration fraction (FF) decreased in all patients during the first course of
      treatment. The values measured 3 weeks after the second course, however, did not
      differ from baseline. CONCLUSIONS: Fostriecin induces reversible renal
      hemodynamic changes compatible with renal tubular damage.

PMID- 9654118
TI  - Comparison of the pharmacokinetics and efficacy of irinotecan after
      administration by the intravenous versus intraperitoneal route in mice.
AB  - Irinotecan (CPT-11) is a new drug active in colorectal cancer. A comparison was
      made of the efficacy and pharmacokinetics of CPT-11 after i.p. versus i.v.
      administration to mice. We found that i.p. administration of CPT-11 to mice
      bearing C26 colon cancer was more efficient and less toxic than i.v.
      administration; a 100-mg i.p. dose induced an increase in life span equivalent to
      that produced by a 300-mg i.v. dose, and toxic deaths appeared after doses of 400
      mg/kg given i.v. and 800 mg/kg given i.p. Pharmacokinetic parameters of CPT-11
      and SN-38 were compared after i.v. or i.p. administration in mice bearing P388
      leukemia ascites. Peritoneal CPT-11 and SN-38 AUC values were higher after i.p.
      administration than after i.v. injection. Plasmatic AUC values remained
      equivalent. Moreover, peritoneal CPT-11 clearance was 10-fold lower after i.p.
      versus i.v. administration. If the survival and pharmacologic advantage of i.p.
      CPT-11 in the murine model considered can be translated to a safe and practical
      mode of therapy in patients and if local toxicity does not prove to be a major
      adverse effect, then a potentially useful agent could be added to the drugs known
      to be active when given by the i.p. route for adjuvant therapy in colon cancer.

PMID- 9654119
TI  - Glucocorticoid pretreatment reduces the cytotoxic effects of a variety of DNA
      damaging agents on rat tibial growth-plate chondrocytes in vitro.
AB  - It is apparent that cytotoxic chemotherapy used to treat childhood malignancies
      has a major impact on subsequent growth. Our initial studies have demonstrated a
      direct adverse effect of individual glucocorticoids and cytotoxic agents on the
      proliferative capacity of rat tibial growth-plate chondrocytes in vitro. In the
      present study we investigated the interaction between these classes of agents
      using in vitro cultures of chondrocytes and examined the potential of these cells
      to recover from the adverse effects of the drugs as applied either alone or in
      combination. The glucocorticoids prednisolone and dexamethasone significantly
      reduced the growth rate of chondrocytes when present in cultures for 3 days. The
      growth rate increased following the removal of prednisolone and dexamethasone
      from cultures and reached 83.9+/-0.8% and 62.4+/-4.0%, respectively, of the
      control values after 11 days of culture. In contrast, cell numbers were
      significantly reduced when the DNA-damaging agents cisplatin, carboplatin,
      etoposide or actinomycin-D were present in cultures for 3 days. Very little
      recovery of cell growth was observed after removal of the drugs from cultures,
      with cell loss occurring in the cisplatin- and actinomycin-D-treated cultures.
      However, pretreatment of chondrocytes with either of the glucocorticoids
      completely ameliorated the cytotoxic effects of etoposide and carboplatin and
      significantly reduced those of cisplatin and actinomycin-D. Recovery of the cells
      treated with a combination of glucocorticoid and DNA-damaging agent was
      demonstrated by a significant increase in their ability to form colonies in
      suspension culture. Colony numbers were increased by a factor of between 5 and 80
      as compared with the cells receiving medium alone followed by DNA-damaging agent.
      The glucocorticoids offer a protective effect in terms of the reduced
      cytotoxicity of DNA-damaging agents and improve the subsequent clonogenicity and
      recovery of growth-plate chondrocytes. This has important implications for
      treatment schedules involving both cytotoxic agents and glucocorticoids in
      childhood malignancies.

PMID- 9654120
TI  - Indirect evidence for structural changes coupled with QB-. formation in
      photosystem II.
AB  - The thermal blockage of QA-. oxidation was analysed in PS II membrane fragments
      by monitoring flash-induced changes of the relative fluorescence quantum yield as
      a function of temperature. The results obtained reveal: (a) in dark-adapted
      samples the fraction of QA-. that is not reoxidised within a time domain of 10 s
      after the actinic flash increases with lowering the temperature (half-maximum
      effect at 250-260 K), (b) at low temperatures where QA-. generated in dark
      adapted samples remains almost completely reduced, a significant extent of QA-.
      reoxidation arises when samples are used that were preilluminated at room
      temperature by one saturating flash followed by rapid freezing before performing
      the experiment, and (c) the extent of QA-. that is reoxidised at 258 K exhibits a
      characteristic binary oscillation as a function of the number of preillumination
      flashes given at room temperature. Based on these data it is inferred that QB and
      QB-. are located at different equilibrium positions in the QB site. As a
      consequence the formation of QB-. is coupled with significant structural changes
      that require sufficient flexibility of the protein matrix. This general feature
      corresponds with a recently proposed model for the acceptor side reactions of
      anoxygenic bacteria [Stowell, M.H.B., McPhillips, T.M., Rees, D.C., Soltis, S.M.,
      Abresch, E. and Feher, G., Science 276 (1997) 812-816].

PMID- 9654121
TI  - Non-glycosylated human B7-1(CD80) retains the capacity to bind its counter
      receptors.
AB  - Though the cell surface-associated costimulator B7-1(CD80) is known to be highly
      N-glycosylated, the functional significance of this N-glycosylation has not been
      evaluated. Two experimental approaches were taken to assess the influence of N
      glycosylation on human B7-1 function. First, stable K562 transfectants expressing
      human B7-1 were treated with the N-glycosylation inhibitor tunicamycin. This
      treatment reduced the levels of B7-1 at the cell surface as judged by both
      indirect immunofluorescence/flow cytometry and immunoprecipitation analyses.
      Significantly, the non-glycosylated cell surface-associated B7-1 on tunicamycin
      treated cells retained the capacity to bind CTLA-4 x Ig, a soluble derivative of
      the CTLA-4(CD152) counter-receptor. Second, experiments were performed with
      bacterially-produced non-glycosylated derivatives of human B7-1, comprising
      either the complete B7-1 extracellular domain (hB7-1 x ed) or the membrane
      proximal IgC-homologue domain of B7-1 in isolation (hB7-1 x IgC). While the hB7-1
      x IgC derivative failed to bind to CTLA-4, the larger hB7-1 x ed derivative
      associated with CTLA-4 x Ig in cell-free binding assays. Futhermore, recombinant
      hB7-1 x ed effectively blocked B7-1-mediated costimulation in an in vitro T cell
      proliferation assay, suggesting that this soluble non-glycosylated B7-1
      derivative is capable of engaging CD28, the B7 counter-receptor implicated in T
      cell activation. Taken together, these data indicate that the N-glycosylation of
      B7-1 is not required for its association with counter-receptors. Moreover, the
      findings pave the way for the therapeutic use of recombinant bacterial B7-1
      derivatives as competitive inhibitors of B7-mediated signals.

PMID- 9654122
TI  - The visual cycle retinol dehydrogenase: possible involvement in the 9-cis
      retinoic acid biosynthetic pathway.
AB  - The 11-cis-retinol dehydrogenase (11-cis-RoDH) gene encodes the short-chain
      alcohol dehydrogenase responsible for 11-cis-retinol oxidation in the visual
      cycle. The structure of the murine 11-cis-RoDH gene was used to reinvestigate its
      transcription pattern. An 11-cis-RoDH gene transcript was detected in several non
      ocular tissues. The question regarding the substrate specificity of the enzyme
      was therefore addressed. Recombinant 11-cis-RoDH was found capable of oxidizing
      and reducing 9-cis-, 11-cis- and 13-cis-isomers of retinol and retinaldehyde,
      respectively. Dodecyl-beta-1-maltoside used to solubilize the enzyme was found to
      affect the substrate specificity. This is the first report on a visual cycle
      enzyme also present in non-retinal ocular and non-ocular tissues. A possible role
      in addition to its role in the visual cycle is being discussed.

PMID- 9654123
TI  - A study on reducing substrates of manganese-oxidizing peroxidases from Pleurotus
      eryngii and Bjerkandera adusta.
AB  - A novel peroxidase, oxidizing Mn2+ and different aromatic compounds, was
      isolated. Hydroquinones, substituted phenols, dyes, other aromatic compounds and
      Mn2+ were compared as reducing substrates, and conclusions presented in the light
      of a molecular model built by homology modeling. The enzymes showed the fastest
      reaction rates with Mn2+, but the highest affinity corresponded to hydroquinones
      and dyes. Oxidation of Reactive Black 5 (an azo-dye not oxidized by Mn3+) was non
      competitively inhibited by Mn2+. These findings, together with identification of
      putative Mn-binding site (involving Glu36, Glu40, Asp175 and inner heme
      propionate) and long-range electron transfer pathways, indicate that different
      sites are involved in substrate oxidation.

PMID- 9654124
TI  - Requirement of membrane-proximal amino acids in the carboxyl-terminal tail for
      expression of the rat AT1a angiotensin receptor.
AB  - A series of deletion mutants was created to analyze the function of the membrane
      proximal region of the cytoplasmic tail of the rat type 1a (AT1a) angiotensin
      receptor. In transiently transfected COS-7 cells, the truncated mutant receptors
      showed a progressive decrease in surface expression, with no major change in
      binding affinity for the peptide antagonist, [Sar1,Ile8]angiotensin II. In
      parallel with the decrease in receptor expression, a progressive decrease in
      angiotensin II-induced inositol phosphate responses was observed. Alanine
      substitutions in the region 307-311 identified the highly conserved
      phenylalanine309 and adjacent lysine residues as significant determinants of AT1a
      receptor expression.

PMID- 9654125
TI  - Rat dipeptidyl peptidase IV (DPP IV) exhibits endopeptidase activity with
      specificity for denatured fibrillar collagens.
AB  - Dipeptidyl peptidase IV (DPP IV, CD 26) is an integral membrane serine protease
      exhibiting a well characterized exopeptidase activity. The present study shows
      that DPP IV also possesses a novel gelatinase activity and therefore
      endopeptidase activity, which was directly demonstrated by gelatin zymography.
      Protease inhibitor profile analysis showed that the endo- and exopeptidase
      activities of DPP IV share a common active site. Substrate specificity was
      detected for denatured collagen types I, II, III and V suggesting that DPP IV
      might contribute to collagen trimming and metabolism. On the basis of these data
      we propose that DPP IV and the recently sequenced gelatinolytic seprase
      (FAPalpha) represent a new subfamily of gelatinolytic integral membrane serine
      proteases.

PMID- 9654126
TI  - Purification and characterization of alkaline phosphatase containing
      phosphotyrosyl phosphatase activity from the bacterium Prevotella intermedia.
AB  - A novel alkaline phosphatase, designated PiALP, has been purified and
      characterized from Prevotella intermedia ATCC 25611, an anaerobe implicated in
      progressive periodontal disease. The enzyme was a homodimer of apparently
      identical subunits of Mr 54 kDa. Thiol-reducing agents completely inhibited the
      purified enzyme. The enzyme was highly stable even at 80 degrees C. It exhibited
      substantial activity against tyrosine-phosphate-containing Raytide. The
      phosphatase activity was sensitive to orthovanadate and Zn2+ but highly resistant
      to okadaic acid. The amino acid sequence of peptides derived from PiALP showed a
      high degree of identity (65%) with alkaline phosphatases from Zymomonas mobilis
      and Synechococcus. The present results imply that PiALP might represent a new
      family of alkaline phosphotyrosyl phosphatases which has not been described
      previously.

PMID- 9654127
TI  - Sequence and functional characterization of RNase P RNA from the chl alb
      containing cyanobacterium Prochlorothrix hollandica.
AB  - Only a few complete sequences and very limited functional data are available for
      the catalytic RNA component of cyanobacterial RNase P. The RNase P RNA from the
      chl alb containing cyanobacterium Prochlorothrix hollandica belongs to a rarely
      found structural subtype with an extended P15/16 domain. We have established
      conditions for optimal in vitro ribozyme activity, and determined the kinetic
      parameters for cleavage of pre-tRNA(Tyr). Analysis of pre-tRNA mutants revealed
      that the T-stem sequence only plays a modulating role, whereas the CCA end is
      essential for efficient product formation.

PMID- 9654128
TI  - Alternative promoter usage and tissue specific expression of the mouse
      somatostatin receptor 2 gene.
AB  - We have cloned the 5' upstream regulatory region of the mouse somatostatin
      receptor 2 gene. Its genomic organization is novel among all somatostatin
      receptor genes. It contains two previously unrecognized exons, separated by
      introns larger than 25 kb, and three tissue and cell specific alternative
      promoters. The first promoter in front of exon 1 is active only in AtT-20 tumor
      cells. The second promoter, located 5' to exon 2, is used in brain, pituitary,
      adrenals, pancreas, NG 108-15 and AtT-20 cells. Furthermore, it contains putative
      DNA elements for regulation by glucocorticoids, estradiol and cAMP. A third
      promoter, located in exon 3, is additionally used in lung, kidney and spleen.

PMID- 9654129
TI  - TSG-6 interacts with hyaluronan and aggrecan in a pH-dependent manner via a
      common functional element: implications for its regulation in inflamed cartilage.
AB  - Cartilage matrix is stabilised by the interactions of proteins with hyaluronan
      (HA). We compare the pH dependences of HA binding by aggrecan, link protein and
      TSG-6. Aggrecan and link protein exhibit maximal binding across a wide pH range
      (6.0-8.0). TSG-6, a protein that is only produced during inflammation, binds
      maximally at about pH 6.0 but shows a dramatic loss of function with increasing
      pH. TSG-6 also interacts with aggrecan, with a similar pH dependence, and this
      can be inhibited by HA. Thus, a common binding surface on TSG-6 may be involved
      in HA and aggrecan binding. We propose that TSG-6 is involved in matrix
      dissociation and that this is regulated by pH gradients in cartilage.

PMID- 9654130
TI  - Abscisic acid maintains S-type anion channel activity in ATP-depleted Vicia faba
      guard cells.
AB  - The plant hormone abscisic acid (ABA) regulates important developmental and
      stress responses. Recent data show that ABA activates phosphorylation events, but
      whether dephosphorylation events are post-translationally regulated by ABA or
      whether these are constitutive remains unknown. Slow anion channels in the plasma
      membrane of guard cells have been proposed to play an important role during ABA
      induced stomatal closing. Anion channels are deactivated by removal of cytosolic
      ATP. However, when guard cells were treated with ABA and depleted of ATP, anion
      currents remained active. Subsequent removal of extracellular ABA caused
      deactivation of currents. Deactivation of currents was reversed by reintroduction
      of cytosolic MgATP. These data show that anion channels are regulated by ABA even
      in the absence of cytosolic ATP required for kinase-induced phosphorylation
      events and that anion channel activity is maintained by ABA under conditions that
      favor dephosphorylation-induced deactivation. Furthermore, channel activation
      proceeded at high ATP concentrations with nanomolar cytosolic Ca2+ showing a Ca2+
      independent final step in anion channel activation.

PMID- 9654131
TI  - Evidence that protein kinase A activity is required for the basal and tax
      stimulated transcriptional activity of human T-cell leukemia virus type-I long
      terminal repeat.
AB  - The present study was undertaken to investigate the role of protein kinase A
      (PKA) in the control of human T-cell leukemia virus type-I (HTLV-I) long terminal
      repeat (LTR) expression, since this issue is still controversial. For this
      purpose we employed two human T-cell lines; the Jurkat cells in which long
      exposure to diBu-cAMP severely down-regulated the catalytic subunit of PKA (PKA
      C), and H-9 cells in which such exposure markedly increased PKA-C level.
      Transient transfection assays revealed that addition of diBu-cAMP 1 h before or
      after transfection profoundly increased HTLV-I LTR directed CAT expression and
      synergistically enhanced its stimulation by the viral transactivator tax gene
      product in both cell lines. However longer exposure to diBu-cAMP before
      transfection reduced LTR-CAT expression to below its basal level and completely
      abolished its stimulation by tax in Jurkat cells, and this diBu-cAMP inhibitory
      effect could be abrogated by co-transfection of a PKA-C expressing vector. By
      contrast, in H-9 cells, this long exposure to diBu-cAMP continued enhancing LTR
      CAT expression and its tax-mediated transactivation, and this stimulatory effect
      of diBu-cAMP could be diminished by the PKA-specific inhibitor N-12-(p
      bromocinnamylamine)ethyll-5-isoquinolinsulfonamid e (H-89). Notably, in the
      absence of diBu-cAMP treatment H-89 reduced LTR-CAT expression to below its basal
      level and prevented its stimulation by tax in both cell lines. Together these
      findings indicate not only that cAMP-activated PKA stimulates HTLV-I LTR
      expression and its transactivation by tax, but even in the absence of PKA
      activating signals the basal HTLV-I LTR expression as well as its stimulation by
      tax are both dependent on a basal PKA activity.

PMID- 9654132
TI  - Resistance to nitrophenolic herbicides and metronidazole in the cyanobacterium
      Synechocystis sp. PCC 6803 as a result of the inactivation of a nitroreductase
      like protein encoded by drgA gene.
AB  - Dinoseb is a herbicide known to inhibit photosystem II electron transfer like
      DCMU, triazine and phenolic-type herbicides. The mutant Din7 of the
      cyanobacterium Synechocystis sp. PCC 6803, selected for resistance to dinoseb,
      and the mutant Ins2, constructed by the insertion of the kanamycin resistance
      cassette into the drgA gene, were cross-resistant to other nitrophenolic
      herbicides (DNOC, 2,4-dinitrophenol) and to the cell inhibitor metronidazole but
      not to the photosystem II inhibitors DCMU or ioxynil. The Din7 mutant had the
      same characteristics of photosystem II inhibition by dinoseb as the wild type.
      This result suggested the existence of another site for dinoseb inhibition. The
      wild type cells modified dinoseb to a non-toxic product that gave an absorption
      spectrum similar to that of dithionite treated dinoseb containing reduced nitro
      groups. In contrast, the Din7 mutant did not modify dinoseb. These phenomena were
      controlled by the drgA gene encoding a protein which showed similarity to several
      enzymes having nitroreductase activity. The addition of superoxide dismutase to
      the medium relieved the toxic effect of dinoseb in wild type cells but not in
      Din7. It is proposed that in wild type cells of Synechocystis sp. PCC 6803 the
      DrgA protein is involved in detoxification of dinoseb via the reduction of the
      nitro group(s) and this process is accompanied by the formation of toxic
      superoxide anions. Mutations blocking the activity of the DrgA protein lead to
      the development of resistance to nitrophenolic herbicides and metronidazole.

PMID- 9654133
TI  - Characterization of a gene encoding an abscisic acid-inducible type-2 lipid
      transfer protein from rice.
AB  - The cloning and sequence analysis of a novel gene that encodes a type 2 non
      specific lipid transfer-like protein (LTP) from rice is reported. Sequence
      analysis revealed an ORF encoding a protein showing characteristics of the LTP
      proteins. However, rice LTP2 is more similar to heterologous LTPs than to rice
      LTP1, supporting the existence of two distinct families of plant LTPs. Ltp2 mRNA
      is accumulated only in mature seeds. In vegetative tissues, mRNA was only
      detected after treatment with abscisic acid (ABA), mannitol or NaCl. Transient
      expression experiments that the 61 nucleotides upstream of the TATA box,
      containing two ACGT boxes and the motif I, are sufficient for ABA responsiveness
      of the Ltp gene.

PMID- 9654134
TI  - Thrombin induces the association of cyclic ADP-ribose-synthesizing CD38 with the
      platelet cytoskeleton.
AB  - The effect of platelet stimulation on the subcellular localization of CD38, a
      membrane glycoprotein that catalyses the synthesis of cyclic ADP-ribose from beta
      NAD+ was investigated. Treatment of human platelets with thrombin caused the
      association of about 40% of the total ADP-ribosyl cyclase activity with the
      cytoskeleton, through the translocation of the CD38 molecule from the Triton X
      100-soluble to the insoluble fraction. The interaction of CD38 with the
      cytoskeleton was a specific and reversible process, mediated by the binding to
      the actin-rich filaments and was inhibited by treatment of platelets with
      cytochalasin D. This event was regulated by integrin alphaIIb beta3 and platelet
      aggregation as it was prevented by the inhibition of fibrinogen binding and was
      not observed in platelets from a patient affected by Glanzmann thrombasthenia.
      These results demonstrate that the subcellular localization of CD38 can be
      influenced by platelet stimulation with physiological agonists, and that membrane
      CD38 can interact with intracellular proteins.

PMID- 9654135
TI  - Caveolin-mediated regulation of signaling along the p42/44 MAP kinase cascade in
      vivo. A role for the caveolin-scaffolding domain.
AB  - The p42/44 mitogen-activated protein (MAP)-kinase cascade is a well-established
      signal transduction pathway that is initiated at the cell surface and terminates
      within the nucleus. More specifically, receptor tyrosine kinases can indirectly
      activate Raf, which in turn leads to activation of MEK and ERK and ultimately
      phosphorylation of Elk, a nuclear transcription factor. Recent reports have
      suggested that some members of p42/44 MAP kinase cascade can be sequestered
      within plasmalemmal caveolae in vivo. For example, morphological studies have
      directly shown that ERK-1/2 is concentrated in plasma membrane caveolae in vivo
      using immunoelectron microscopy. In addition, constitutive activation of the
      p42/44 MAP kinase cascade is sufficient to reversibly down-regulate caveolin-1
      mRNA and protein expression. However, the functional relationship between the
      p42/44 MAP kinase cascade and caveolins remains unknown. Here, we examine the in
      vivo role of caveolins in regulating signaling along the MAP kinase cascade. We
      find that co-expression with caveolin 1 dramatically inhibits signaling from EGF
      R, Raf, MEK-1 and ERK-2 to the nucleus. Using a variety of caveolin-1 deletion
      mutants, we mapped this in vivo inhibitory activity to caveolin-1 residues 32-95.
      Peptides derived from this region of caveolin 1 also inhibit the in vitro kinase
      activity of purified MEK-1 and ERK-2. Thus, we show here that caveolin-1
      expression can inhibit signal transduction from the p42/44 MAP kinase cascade
      both in vitro and in vivo. Taken together with previous data, our results also
      suggest that a novel form of reciprocal negative regulation exists between p42/44
      MAP kinase activation and caveolin-1 protein expression, i.e. up-regulation of
      caveolin-1 protein expression down-modulates p42/44 MAP kinase activity (this
      report) and up-regulation of p42/44 MAP kinase activity down-regulates caveolin-1
      mRNA and protein expression.

PMID- 9654137
TI  - Cloning and sequencing of ISC1041 from the archaeon Sulfolobus solfataricus MT-4,
      a new member of the IS30 family of insertion elements.
AB  - A genomic fragment containing the insertion sequence ISC1041 has been cloned by
      PCR from the archaeon Sulfolobus solfaricus MT-4, an extremophilic microorganism
      which grows at 87 degrees C. The 1038 bp ISC1041 element contains an imperfect 18
      nt repeat and a long open reading frame which encodes a polypeptide of 311 amino
      acid residues. The translated amino acid sequence shows a significant similarity
      to IS30-like transposases. Structural analysis indicates that ISC1041 is a novel
      member of the IS30 family and displays the DDE motif not previously seen in
      Archaea. This motif is believed to be involved in the integration mechanism of
      many mobile elements. As this motif is present in several integrases and
      transposases which, despite the lack of overall protein homologies, share
      topological homologies to the DDE motif, a common ancestor has been proposed. The
      finding of an IS30-like transposase in the archaeal kingdom may have relevance
      for horizontal gene transfer.

PMID- 9654136
TI  - Coexpression of GTP cyclohydrolase I and inducible nitric oxide synthase mRNAs in
      mouse osteoblastic cells activated by proinflammatory cytokines.
AB  - Proinflammatory cytokines, a combination of IL-1beta, TNF-alpha, and IFN-gamma,
      caused mRNA expression of GTP cyclohydrolase I (GTP-CH), the rate-limiting enzyme
      in tetrahydrobiopterin (BH4) biosynthesis, and of inducible nitric oxide synthase
      (iNOS) in a well-characterized osteoblastic clone MC3T3-E1 cell line. We found
      the expression of the GTP-CH gene in osteoblasts for the first time. The
      expression of GTP-CH and iNOS mRNAs was found to be maximal at 3 and 9 h,
      respectively. The expression of both genes elicited increases in BH4 and NO
      levels. Pharmacological studies using 2,4-diamino-6-hydroxypyrimidine, an
      inhibitor of GTP-CH activity, showed that BH4 is involved in the activity of
      iNOS, but not in the induction of iNOS mRNA. The results using an inhibitor of
      nuclear factor (NF)-kappaB and activating protein-1 (AP-1) activation suggested
      that coinduction of the two genes in response to cytokines occurred via
      activation of NF-kappaB and AP-1. In MC3T3-E1 cells BH4 and sepiapterin,
      producing BH4, could protect against apoptosis, i.e. the degradation of nuclear
      DNA in the cells, induced by NO derived from S-nitroso-N-acetyl-D-L
      penicillamine. These results suggest that the induction of BH4 together with NO
      by proinflammatory cytokines could protect against NO-induced apoptosis in MC3T3
      E1 cells.

PMID- 9654138
TI  - HrpW of Erwinia amylovora, a new Hrp-secreted protein.
AB  - Erwinia amylovora strain CFBP1430 secretes a protein called HrpW in a Hrp
      dependent manner. HrpW was detected in culture supernatant of the wild-type
      strain grown on solid inducing hrp medium. This protein shares structural
      similarities with elicitors of the hypersensitive response such as HrpN of
      Erwinia amylovora and PopA of Ralstonia solanacearum. Furthermore, the C-terminal
      region of HrpW is homologous to class III pectate lyases. An hrpW mutant is as
      aggressive as the wild-type strain on pear and apple seedlings. It elicits the
      hypersensitive response on tobacco at a lower concentration than the wild-type
      strain.

PMID- 9654139
TI  - An Arabidopsis cDNA encoding a bifunctional glutamine amidotransferase/cyclase
      suppresses the histidine auxotrophy of a Saccharomyces cerevisiae his7 mutant.
AB  - A cDNA encoding a glutamine amidotransferase and cyclase catalyzing the fifth and
      sixth steps of the histidine (His) biosynthetic pathway has been isolated from
      Arabidopsis thaliana. The N- and C-terminal domains of the primary structure
      deduced from a full-length Arabidopsis hisHF (At-HF) cDNA showed significant
      homology to the glutamine amidotransferase and cyclase of microorganisms,
      respectively. Effective suppression of the His auxotrophy of a Saccharomyces
      cerevisiae his7 mutant with the At-HF cDNA confirmed that the At-HF protein has
      bifunctional glutamine amidotransferase (HisH) and cyclase (HisF) activities.

PMID- 9654140
TI  - Biochemical characterization of HIV-1 Rev as a potent activator of casein kinase
      II in vitro.
AB  - The stimulatory effects of several DNA-binding basic proteins (histone and
      protamine) and HIV-1 Rev with arginine (Arg)-rich clusters on the activity of
      casein kinase II (CK-II) were investigated in vitro. It was found that
      recombinant Rev (rRev) and the synthetic oligo-fragments corresponding to the
      amino acid sequences of its Arg-rich cluster stimulate CK-II activity in a dose
      dependent manner. The activated CK-II phosphorylates several cellular and viral
      proteins in HIV-1 infected human MOLT-4 cells, and also phosphorylates HIV-1
      structural proteins, including recombinant reverse transcriptase (rRT). These
      phosphorylations are selectively inhibited by CK-II inhibitors, such as
      quercetin, oGA (a glycyrrhetinic acid derivative) and NCS-chrom (an enediyne
      containing antibiotic). The data presented here suggest that HIV-1 Rev acts as an
      effective potent activator of CK-II, which may be a cellular mediator promoting
      HIV-1 replication in virus-infected cells.

PMID- 9654141
TI  - Characterisation of an Arabidopsis cDNA encoding a thylakoid lumen protein
      related to a novel 'pentapeptide repeat' family of proteins.
AB  - We have cloned an Arabidopsis cDNA encoding a novel thylakoid lumen protein,
      P17.4, that has been previously isolated from lumen extracts of spinach
      chloroplasts. The protein is synthesised with a bipartite presequence containing
      a Sec-type lumen-targeting signal peptide and the precursor protein is imported
      into the lumen of pea chloroplasts. The encoded protein is homologous to an
      Anabaena protein that is essential for correct glycolipid localisation, and is
      also related to at least 16 unassigned open reading frames in Synechocystis. This
      family of proteins is characterised by the presence of numerous pentapeptide
      repeats with the consensus structure AXLXX, and its members are predicted to be
      located in the cytosol, plasma membrane and periplasm/lumen. P17.4 is therefore
      the first higher plant member of an extended family of putative cyanobacterial
      proteins that may serve important roles in lipid transport or assembly.

PMID- 9654142
TI  - Saccharomyces cerevisiae mitochondria can synthesise FMN and FAD from externally
      added riboflavin and export them to the extramitochondrial phase.
AB  - Evidence is given that mitochondria isolated from Saccharomyces cerevisiae can
      take up externally added riboflavin and synthesise from it both flavin
      mononucleotide (FMN) and flavin adenine dinucleotide (FAD) probably due to the
      existence of the mitochondrial riboflavin kinase already reported and the novel
      mitochondria FAD synthetase. Moreover Saccharomyces cerevisiae mitochondria can
      export the newly synthesised flavin derivatives to the extramitochondrial phase.
      This has been proven to take place with 1:1 stoichiometry with riboflavin
      decrease outside mitochondria, thus showing that flavin traffic occurs across the
      mitochondrial membranes.

PMID- 9654143
TI  - A non-peptide compound which can mimic the effect of thrombopoietin via c-Mpl.
AB  - Thrombopoietin (TPO) is a cytokine which plays a central role in megakaryopoiesis
      and platelet production by binding to its cell surface receptor, termed c-Mpl. In
      the present study, two benzodiazepinones that compete with the binding of TPO to
      the extracellular region of c-Mpl were identified, and one of them stimulated the
      proliferation of a human TPO-dependent megakaryocytic cell line, UT-7/TPO. It
      stimulated the activation of signal transducer and activator of transcription 5
      in UT-7/TPO cells. These results suggest that a non-peptide compound can mimic
      the effect of TPO via c-Mpl.

PMID- 9654144
TI  - The functional properties of DsbG, a thiol-disulfide oxidoreductase from the
      periplasm of Escherichia coli.
AB  - Genetic studies have recently identified DsbG, a new member of the dsb group of
      redox proteins, which catalyze protein disulfide bond formation in the periplasm
      of Escherichia coli. We now demonstrate that DsbG functions primarily as an
      oxidant during protein disulfide bond formation, which is consistent with the low
      stability of its active site disulfide bond. There are indications, however, that
      the substrate range of DsbG may be narrower than the other periplasmic oxidative
      enzymes, DsbA and DsbC. Our observations further elaborate the pathway of
      disulfide bond formation in E. coli.

PMID- 9654145
TI  - A novel importin alpha from rice, a component involved in the process of nuclear
      protein transport.
AB  - In eukaryotes, nuclear proteins that are transported into nuclei have nuclear
      localization signals (NLSs), which are recognized by proteins called importin
      alpha. We isolated a rice cDNA, #61L, and the corresponding gene that encodes a
      protein, which shows significant homology to the importin alpha. Although the
      encoded protein had only 23-27% amino acid identity to the importin alphas from
      various organisms including plants, the fusion protein with glutathione S
      transferase showed a specific binding activity to the NLS of SV40 T-antigen.
      These results suggest that the rice #61L protein is a novel importin alpha in
      plants.

PMID- 9654146
TI  - Purification and characterisation of a new hypothalamic satiety peptide, cocaine
      and amphetamine regulated transcript (CART), produced in yeast.
AB  - Cocaine and amphetamine regulated transcript (CART) is a newly discovered
      hypothalamic peptide with a potent appetite suppressing activity following
      intracerebroventricular administration. When the mature rat CART sequence
      encoding CART(1-102) was inserted in the yeast expression plasmid three CART
      peptides could be purified from the fermentation broth reflecting processing at
      dibasic sequences. None of these corresponded to the naturally occurring CART(55
      102). In order to obtain CART(55-102) the precursor Glu-Glu-Ile-Asp-CART(55-102)
      has been produced and CART(55-102) was generated by digestion of the precursor
      with dipeptidylaminopeptidase-1. All four generated CART peptides have been
      characterised by N-terminal amino acid sequencing and mass spectrometry. The CART
      peptides contain six cysteine residues and using the yeast expressed CART(62-102)
      the disulphide bond configuration was found to be I-III, II-V and IV-VI. When the
      four CART peptides were intracerebroventricularly injected in fasted mice (0.1 to
      2.0 microg) they all produced a dose dependent inhibition of food intake.

PMID- 9654147
TI  - The solution structure of DNA decamer duplex containing the Dewar product of
      thymidylyl(3-->5')thymidine by NMR and full relaxation matrix refinement.
AB  - The (6-4) adducts and their Dewar isomers play an important role in cytotoxicity
      and mutation in skin cells exposed to sunlight. Structural study of the DNA
      duplex containing a site-specific photoproduct is an essential step toward
      understanding the molecular mechanism of the mutagenesis and the repair activity
      of UV-irradiated DNA. Here we use 1H NMR spectroscopy and full relaxation matrix
      refinement to investigate the solution structure of the duplex Dewar decamer. We
      find that the isomerization of the (6-4) adduct to its Dewar form induces a
      substantial change in overall structure of the oligonucleotide duplex.
      Contrasting base stacking of two lesion sites results in a large difference in
      the structural impacts induced by the two photoproducts, such as differential
      disruption of hydrogen bonding at the lesion sites and overall helical bending of
      44 degrees by the (6-4) lesion and 21 degrees by the Dewar lesion.

PMID- 9654148
TI  - Promoter elements required for sugar-repression of the RAmy3D gene for alpha
      amylase in rice.
AB  - There is increasing evidence showing that cereal alpha-amylase gene expression is
      controlled not only by the classical hormonal regulation, but also by feed-back
      sugar repression. We demonstrated by in situ hybridization that the sugar
      repression of rice alpha-amylase gene RAmy3D takes place in scutellar epithelium
      cells of callus-forming rice embryos. We also used a transient expression system
      to study the cis-acting elements involved in the sugar repression of the RAmy3D
      promoter activity. Site-directed mutagenesis of the 50-bp nucleotide sequence
      from -172 to -123 revealed that consensus sequences of G motif (TACGTA) and
      TATCCA T/C motif (GATA motif as its antisense sequence) are responsible for sugar
      repression. The promoter sequences required for sugar repression are reported and
      discussed.

PMID- 9654149
TI  - Analysis of functional domains of Wilson disease protein (ATP7B) in Saccharomyces
      cerevisiae.
AB  - Wilson disease is a genetic disorder of copper metabolism characterized by the
      toxic accumulation of copper in the liver. The ATP7B gene, which encodes a copper
      transporting P-type ATPase, is defective in patients with Wilson disease. To
      investigate the function of ATP7B, wild type or mutated ATP7B cDNA was introduced
      into a yeast strain lacking the CCC2 gene (delta ccc2), the yeast homologue of
      ATP7B. Wild type and the H1069Q mutant could rescue delta ccc2, however, the
      N1270S mutant could not, reflecting phenotypic variability of Wilson disease. In
      addition, the mutant containing only the sixth copper binding domain could rescue
      delta ccc2, indicating its functional importance.

PMID- 9654150
TI  - LVV- and VV-hemorphins: comparative levels in rat tissues.
AB  - Screening of hemorphins in extracts of rat lung, brain, heart and spleen was
      carried out. The threshold for detection of hemorphins was 0.01 nmol for spleen
      and 0.05 nmol for other tissues. Both the content and the composition of
      hemorphins differed significantly in the tissues analyzed. Heart and lung
      extracts were rich in these peptides, the content of the most abundant components
      reaching 16-44 nmol/g of tissue. In contrast, spleen and brain contained much
      lower amounts of hemorphins, i.e. about 0.3-2.6 nmol/g of tissue. The most
      represented hemorphin in lung, heart and brain was VV-hemorphin-5, while the
      content of other members of the hemorphin family depended significantly on the
      tissue analyzed: lung extract was also rich in LVV-hemorphin-5, heart contained
      similar amounts of LVV-hemorphin-7 and LVV-hemorphin-5 and brain of LVV-hemorphin
      6. In contrast, the hemorphin family in spleen was represented mainly by C
      terminally shortened VV-hemorphins, i.e. VV-hemorphin-4 and VV-hemorphin-3. The
      levels of hemorphins in all cases were sufficient to activate the opioid
      receptors of the respective tissues.

PMID- 9654151
TI  - Human substance P receptor expressed in Chinese hamster ovary cells directly
      activates G(alpha q/11), G(alpha s), G(alpha o).
AB  - Substance P receptor (SPR) stably expressed in Chinese hamster ovary (CHO) cells
      stimulates at least three second messenger systems including phosphoinositide
      hydrolysis, cyclic AMP (cAMP) formation, and arachidonic acid release. Whether
      these second messenger systems are activated via single or multiple G proteins is
      not known. Therefore, in the present study we examined whether human SPR (hSPR)
      stably expressed in CHO cells activates multiple G proteins. This was achieved by
      photoaffinity labeling of G(alpha)-subunits with [32P]azidoanilido-GTP ([32P]AA
      GTP) upon hSPR stimulation in CHO-hSPR membranes followed by immunoprecipitation
      of the labeled G(alpha)-subunits with antibodies specific for various G(alpha)
      subunits. These experiments reveal that hSPR directly activates G(alpha q/11),
      G(alpha s) and G(alpha o). While hSPR is known to couple G(alpha q/11), the
      present study provides the first evidence that hSPR can also activate G(alpha s)
      and G(alpha o) in a mammalian system.

PMID- 9654152
TI  - The F420H2:heterodisulfide oxidoreductase system from Methanosarcina species. 2
      Hydroxyphenazine mediates electron transfer from F420H2 dehydrogenase to
      heterodisulfide reductase.
AB  - F420H2-dependent CoB-S-S-CoM reduction as catalyzed by the F420H2:heterodisulfide
      oxidoreductase from Methanosarcina strains was observed in a defined system
      containing purified F420H2 dehydrogenase from Methanosarcina mazei Go1, 2
      hydroxyphenazine and purified heterodisulfide reductase from Methanosarcina
      thermophila. The process could be divided into two partial reactions: (1)
      reducing equivalents from F420H2 were transferred to 2-hydroxyphenazine by the
      F420H2 dehydrogenase with a Vmax value of 12 U/mg protein; (2) reduced 2
      hydroxyphenazine acted as electron donor for CoB-S-S-CoM reduction as catalyzed
      by the heterodisulfide reductase. The specific activity was 14-16 U/mg protein at
      37 degrees C and 60-70 U/mg protein at 60 degrees C. The partial reactions could
      be combined in the presence of both enzymes. Under these conditions reduced 2
      hydroxyphenazine was rapidly oxidized by the heterodisulfide reductase thereby
      producing the electron acceptor for the F420H2 dehydrogenase. Above a
      concentration of 50 microM of 2-hydroxyphenazine, the specific activity of the
      latter enzyme reached the Vmax value. When other phenazines or quinone
      derivatives were used as electron carriers, the activity of F420H2-dependent CoB
      S-S-CoM reduction was much lower than the rate obtained with 2-hydroxyphenazine.
      Thus, this water-soluble analogue of methanophenazine best mimics the natural
      electron acceptor methanophenazine in aqueous systems.

PMID- 9654153
TI  - Purification and characterization of alpha-3',4'-anhydrovinblastine synthase
      (peroxidase-like) from Catharanthus roseus (L.) G. Don.
AB  - An H2O2-dependent enzyme capable of coupling catharanthine and vindoline into
      alpha-3',4'-anhydrovinblastine (AVLB) was purified to apparent homogeneity from
      Catharanthus roseus leaves. The enzyme shows a specific AVLB synthase activity of
      1.8 nkat/mg, and a molecular weight of 45.40 kDa (SDS-PAGE). In addition to AVLB
      synthase activity, the purified enzyme shows peroxidase activity, and the VIS
      spectrum of the protein presents maxima at 404, 501 and 633 nm, indicating that
      it is a high spin ferric heme protein, belonging to the plant peroxidase
      superfamily. Kinetic studies revealed that both catharanthine and vindoline were
      substrates of the enzyme, AVLB being the major coupling product.

PMID- 9654154
TI  - Purification of a novel endothelin-converting enzyme specific for big endothelin
      3.
AB  - Endothelin-3 (ET-3), a potent vasoactive peptide, is considered to be produced
      from big ET-3 by endothelin-converting enzyme (ECE) like the other members of the
      endothelin family (ET-1 and ET-2). We purified a novel ECE from bovine iris
      microsomes. The purified enzyme, a 140 kDa protein by SDS-PAGE analysis,
      converted big ET-3 to ET-3 but not big ET-1, with a Km value of 0.14 microM for
      big ET-3. The conversion to ET-3 was confirmed with sandwich EIA by monoclonal
      antibodies, the elution profile of HPLC, and intracellular calcium mobilization
      in CHO-K1 cells expressing recombinant human ET(B) receptors. The conversion
      activity was inhibited by an inhibitor of neutral endopeptidase 24.11 (NEP)
      phosphoramidon. These results show that ECE-3 purified from bovine iris is a
      novel metalloprotease totally different from ECE-1 or ECE-2, in that the enzyme
      is highly specific for big ET-3.

PMID- 9654155
TI  - Long-term therapeutic efficacy and toxicity of recombinant interferon-alpha 2a in
      polycythaemia vera.
AB  - We report on long-term therapeutic efficacy and toxicity of recombinant
      interferon-alpha 2a (rIFN-alpha) in a series of 38 patients with polycythaemia
      vera (PV). In all patients haematocrit was first brought into the normal range by
      venesection; rIFN-alpha was then begun at a starting weekly dose of 9,000,000 IU.
      Complete response (CR) was defined as persistence of normal haematocrit without
      venesection and partial response (PR) as >50% reduction of phlebotomy
      requirement. Eleven patients (28.9%) achieved CR and 8 (21.0%) PR. Median
      duration of treatment for all responsive patients was 40 months; 12 patients are
      still responsive and under treatment after 13, 15, 25, 35, 40, 41, 43, 49, 50,
      51, 52 and 52 months of therapy with rIFN-alpha. In responsive patients, rIFN
      alpha also normalized leucocyte counts, platelet counts and spleen enlargement;
      rIFN-alpha also relieved generalized pruritus in all 10 patients displaying this
      symptom. Early toxicity (flu-like syndrome) was observed in 23.6% and late
      toxicity (severe weakness) in 13.1% of patients, requiring rIFN-alpha treatment
      suspension in all cases. Progression to leukaemia was observed in none of the 10
      patients treated only with rIFN-alpha and in one of the 12 who received
      alkylating agents before enrolment in this study. According to these data, rIFN
      alpha seems to be an effective and safe treatment option for PV.

PMID- 9654156
TI  - Plasma erythropoietin by high-detectability immunoradiometric assay in untreated
      and treated patients with polycythaemia vera and essential thrombocythaemia.
AB  - By using an immunoradiometric method with a stated detection limit of < or =1
      IU/l (stated normal reference limit in adults 3.7-16 IU/l) we determined EDTA
      plasma erythropoietin (EPO) in 58 patients with polycythaemia vera (PV) and 49
      patients with essential thrombocythaemia (ET). At the time of blood sampling, 20
      of the PV patients were newly diagnosed and untreated, 23 were treated by
      phlebotomy only, and 30 also received myelosuppressive treatment (with 32P,
      hydroxyurea or alpha-interferon). Of the ET patients 24 were untreated and 28
      received myelosuppressive therapy. For comparison plasma EPO was also determined
      in 10 patients with pseudopolycythaemia (PP). In this latter group the results
      for plasma EPO agreed well with the cited normal reference limits. The majority
      of untreated PV patients (12/20) had undetectable plasma EPO concentration, and
      the remainder all had values below the lower normal reference limit. Plasma EPO
      in PV was not significantly influenced by phlebotomy therapy. Twelve of the 24
      untreated ET patients (50%) had plasma EPO values below the reference interval
      (undetectable in 2 patients). The mean EPO concentration was significantly lower
      in PV patients receiving phlebotomy therapy than in patients with untreated ET.
      In the total material of PV and ET treated with myelosuppressive agents the PV
      patients showed significantly lower values for EPO concentration than did
      patients with ET. The present results support the view that EPO measurements by
      high-detectability methods are diagnostically useful and should be included in
      the panel of new criteria for the diagnosis of PV.

PMID- 9654157
TI  - Antibodies against platelet glycoproteins and antiphospholipid antibodies in
      autoimmune thrombocytopenia.
AB  - Autoantibodies against platelet glycoproteins (anti-GP) are found in the majority
      of patients with autoimmune thrombocytopenia (AITP) as well as in
      thrombocytopenia associated with systemic lupus erythematosus (SLE). Some of
      these patients may have anti-phospholipid antibodies (anti-PL). To evaluate the
      pathogenetic significance of anti-PL and anti-GP antibodies in AITP and SLE
      patients, we investigated anti-cardiolipin (anti-CL), anti-phosphatidylserine
      (anti-PS) and anti-GP antibodies (anti-GPIIb-IIIa and anti-GPIb-IX) in 71
      patients with AITP and 3 thrombocytopenic patients with SLE. Anti-GP antibodies
      were detected in 52 (70%) patients. Fifty-six (73%) patients showed anti-PL
      antibodies. Seven patients (6 AITP, 1 SLE) with both anti-GPIIb-IIIa and IgG anti
      PL antibodies were followed during treatment with corticosteroids. Antibodies
      were measured before treatment and at the time of platelet-peak. Anti-GPIIb-IIIa
      antibodies decreased in all or became undetectable in five. In contrast, IgG anti
      PS and IgG anti-CL antibodies decreased only moderately or remained positive.
      Adsorption experiments, using gelfiltered platelets, erythrocyte (Ec)-inside-out
      vesicles and purified GPIIb-IIIa, showed that anti-GP and anti-PL antibodies have
      distinct specificities and do not crossreact. We conclude that anti-PL and anti
      GP antibodies may be present simultaneously in some patients with immune mediated
      thrombocytopenia. Although anti-PS as well as anti-CL antibodies may be
      responsible for thrombocytopenia, we speculate that anti-GPIIb-IIIa antibodies
      are more related to the severity of thrombocytopenia.

PMID- 9654158
TI  - Serum soluble c-kit receptor and expression of c-kit protein and mRNA in acute
      myeloid leukemia.
AB  - To investigate the clinical role of the soluble form of c-kit receptor (s-kit) in
      patients with acute myeloid leukemia (AML), we determined the levels of serum s
      kit and expression of c-kit antigens and mRNA in leukemic cells. The serum s-kit
      level was measured using ELISA assay in 30 AML patients and 20 normal controls. C
      kit antigens of leukemic blasts were stained immunohistologically, and c-kit mRNA
      was detected by RT-PCR. The serum s-kit level in M1 and M2 were significantly
      increased (p<0.01) and that in M4 or M5 was significantly decreased (p<0.05)
      compared to that in the controls. In the comparisons among subtypes of FAB
      classification, M1 and M2 showed significantly higher levels than M4 or M5
      (p<0.05 and p<0.01, respectively). Both expression of c-kit antigens and mRNA
      were observed in M0 (1/4), M1 (2/4) and M2 (6/8), but neither was observed in M4
      or M5. The serum s-kit levels were correlated with the absolute number of AML
      blasts in peripheral blood (r=0.564, p<0.05). These results indicate that the
      serum s-kit level is related to the stage of differentiation of AML blasts in
      accordance with the expression of c-kit protein and mRNA in AML blasts, and is
      useful for assessment of leukemic cell burden.

PMID- 9654159
TI  - Haematopoietic action of flt3 ligand on cord blood-derived CD34-positive cells
      expressing different levels of flt3 or c-kit tyrosine kinase receptor: comparison
      with stem cell factor.
AB  - We compared the effect of human flt3 ligand (FL) and stem cell factor (SCF) on
      cord blood (CB)-derived CD34+ cells expressing different levels of flt3 or c-kit
      tyrosine kinase (TK) receptor in clonal cell culture. The c-kit receptor was
      expressed by 58.5+/-16.7% of CB CD34+ cells (n=19), in which c-kit(high), c
      kit(low) and c-kit cell populations could be identified. In contrast, the flt3
      receptor (FR) was weakly expressed on 58.6+/-8.3% (n=9) of CB CD34+ cells.
      FL+erythropoietin (Epo) failed to support erythroid burst (BFU-E) formation by
      any subpopulation of CD34+ cells. However, SCF + Epo supported BFU-E and
      erythrocyte-containing mixed (CFU-mix) colony formation from all subpopulations.
      Interestingly, FL markedly augmented CFU-mix colony formation supported by
      interleukin (IL)-3 + Epo when CD34+c-kit(low) or CD34+FR+ cells were used as the
      target. On the other hand, SCF significantly enhanced CFU-mix colony formation
      supported by IL-3 + Epo when CD34+c-kit(high) or low and CD34+FR+ cells were
      used. The replating potential of CFU-mix supported by IL-3 + Epo+ FL was greater
      when CD34+c-kit(low) or CD34+FR+ cells were used. When the CD34+c-kit(low) cells
      were used, the number of lineages expressed in secondary cultures of CFU-mix
      colonies derived from primary cultures containing IL-3 + Epo + FL or SCF was
      significantly larger than when the primary cultures contained IL-3 + Epo.
      Furthermore, the number of long-term culture-initiating cells found in CD34+FR+
      cells was larger than that in FR cells. CB-derived CD34+c-kit(low) cells
      represent a less mature population than c-kit(high) cells, as reported
      previously. Therefore, these results indicate that both FL and SCF can act on
      primitive multipotential progenitors. However, it is still uncertain whether CB
      derived CD34+FR+ cells are less mature than CD34+FR- cells.

PMID- 9654160
TI  - Relative distribution of myosin, actin and alpha-actinin in surface-activated,
      spreading platelets.

PMID- 9654161
TI  - Acute megakaryocytic leukaemia (AML-M7) with myelofibrosis terminating in AML-MO
      with concurrent liver fibrosis.

PMID- 9654162
TI  - Low dose bolus aminocaproic acid: an alternative to platelet transfusion in
      thrombocytopenia?

PMID- 9654163
TI  - Serum erythropoietin values and serum iron status during chemotherapy for
      leukemia.

PMID- 9654164
TI  - Recombinant human erythropoietin for the treatment of refractory anemia in
      lymphoproliferative disorders: preliminary results.

PMID- 9654165
TI  - Detection of chronic systemic candida infection in leukaemia patients with
      febrile neutropenia: value of computer-assisted serial ultrasound documentation.

PMID- 9654166
TI  - Have the Fallopian tubes a vital role in promoting fertility?
AB  - Diverse lines of evidence suggest that the Fallopian tubes make no overwhelming
      contribution to human reproduction other than as a conduit for gametes and
      embryos. Even so, bearing in mind global success rates for in vitro fertilization
      (IVF) coupled with uterine transplantation of embryos (20% fruitful pregnancies),
      the Fallopian tubes may make a subtle contribution to reproductive performance.
      The experimental evidence from monkeys and man arguing against an essential role
      for the tubes -- at least in individual instances -- would include (1) the
      results of Estes' operation, when ovaries are autotransplanted into the uterine
      lumen in women with blocked or missing Fallopian tubes and pregnancy ensues; (2)
      asynchronous embryo transfer when newly fertilized (pronucleate) eggs
      transplanted to the uterus can generate a pregnancy; (3) the transcervical
      transfer after IVF of early cleavage stage human embryos into the uterus, with
      subsequent establishment of pregnancy; (4) the trans-cervical transfer of human
      spermatozoa and oocytes into the uterus to give pregnancy, indicating that
      capacitation, fertilization and the earliest stages of embryonic development can
      be achieved in the uterus. In endeavoring to explain contrasts between these
      successful procedures in primates and their failure in non-primates, perhaps the
      simplex uterus in primates compared with a bicornuate or bipartite uterus in
      laboratory and farm species has relevance: there is lack of a clear-cut
      distinction between the endometrium and endosalpinx in the intra-mural segment
      and potential mixing of uterine and tubal fluids. Indeed, the latter may explain
      in part a susceptibility to tubal ectopic pregnancy, coupled with proliferating
      endometrial fragments in the Fallopian tube.

PMID- 9654167
TI  - Synergistic effects of growth hormone and insulin-like growth factor-I on
      differentiation and replication of cultured human luteinized granulosa cells.
AB  - BACKGROUND: The present study was designed to assess the effects of insulin-like
      growth factor-I (IGF-I) alone and in combination with growth hormone (GH) on
      differentiation and replication in cultured human granulosa cells. METHODS:
      Granulosa cells from patients undergoing in vitro fertilization were isolated and
      cultured for 2 days in culture medium with 10% serum, the medium was removed and
      the cells were incubated with IGF-I (1, 10 and 100 ng/ml) with or without GH (10
      ng/ml) in serum-free medium and in the presence of 3H-methylthymidine (2
      microCi/ml). RESULTS: IGF-I alone resulted in a significant dose-dependent
      increase in medium estradiol (E2) (p<0.05) and progesterone (P) (p<0.001) and
      suppression of IGF-binding protein-1 (IGFBP-1) (p<0.001), without any increase in
      [3H]-thymidine incorporation (P=0.10). The combination of IGF-I and GH further
      increased the release of E2 (p<0.001), and the amount of [3H]-thymidine
      incorporation (p<0.001). CONCLUSION: These results indicate a synergistic effect
      of IGF-I and GH on differentiation and replication of human granulosa cells, and
      thus support a role of both GH and IGF-I in regulation of ovarian function.

PMID- 9654168
TI  - Placental expression of endothelial constitutive nitric oxide synthase mRNA in
      pregnancy complicated by preeclampsia.
AB  - BACKGROUND: The role of nitric oxide (NO) in normal pregnancy and pregnancy
      complicated with preeclampsia (PE) and/or intrauterine growth restriction (IUGR)
      still remains questionable. The placenta lacks autonomic innervation, therefore
      blood flow must be regulated by humoral and endothelium derived factors. NO is a
      potent vasodilator released by endothelial cells. It is synthesized by the
      catalytic action of the endothelial constitutive nitric oxide synthase (ecNOS).
      Moreover, the synthesis of NO in normal human placental vasculature has already
      been established and impairment of the uteroplacental blood flow in pregnancies
      complicated by PE and/or IUGR has been demonstrated. DESIGN AND METHODS: The aim
      of the present study was to compare the expression of ecNOS mRNA in placenta from
      women with complicated and normal pregnancies. Placenta was collected from women
      with PE (n = 13) or small for gestational age (SGA) (n = 8), both PE and SGA (n =
      7) and normal pregnancies (n = 41). Total nucleic acids were prepared and a
      solution hybridization technique was used for mRNA analysis. RESULT: The mRNA
      expression of ecNOS was significantly higher (p<0.05) in all groups of
      complicated pregnancies compared to normal pregnancies. CONCLUSION: Our findings
      indicate that the increased placental expression of ecNOS mRNA might reflect a
      compensatory mechanism in the disturbed uterine circulation seen in PE and/or
      SGA.

PMID- 9654169
TI  - Nuchal translucency as a screening test for chromosomal abnormalities in a
      routine first trimester ultrasound examination.
AB  - BACKGROUND: To evaluate the implementation of nuchal translucency measurement as
      an additional examination within the first trimester routine ultrasound in an
      unselected population of women. METHODS: A prospective study in which all
      pregnant women during 1994, referred for the first trimester routine ultrasound
      scan, were asked to participate. Of a total of 1852 women with a viable
      pregnancy, results from 1444 women were evaluated. When a nuchal translucency of
      4 mm or more was found, the woman was offered both a genetic amniocentesis in
      gestational week 13-15 and an additional ultrasound examination in gestational
      week 18-19. RESULTS: Six fetuses had a nuchal translucency of 4 mm or more and
      none of these had any chromosomal abnormality. Neither had any of the fetuses in
      the study, karyotyped for other reasons, any chromosomal defect and nor was there
      any child born with aneuploidy in the study population. No strong relation
      between major malformations e.g. abnormalities of the heart and increased nuchal
      translucency was found. The fetus with the largest nuchal translucency (=6 mm)
      was born healthy. CONCLUSION: The efficacy of nuchal translucency measurement
      needs further evaluation before it can be introduced as a screening method in an
      unselected pregnant population.

PMID- 9654170
TI  - Consumption of anti-D in the erythroblastotic fetus.
AB  - BACKGROUND: Maternal serum anti-D is actively transported across the placenta
      into the fetal blood where it adheres to D-positive erythrocytes. The anti-D
      coated red cells attach to Fc-receptors on fetal reticuloendothelial cells and
      are subsequently phagocytosed and hemolysed. It is not known if anti-D is
      consumed or recirculated in this process. MAIN QUESTION: Is anti-D in the fetus
      consumed in the hemolytic process in the erythroblastotic fetus and can the
      consumption be modulated by high-dose immunoglobulins (i.v.IG) given to the
      mother? METHODS: Fetal/maternal serum anti-D concentration ratios were calculated
      for simultaneously taken blood samples from three groups of Rh(D) immunized
      pregnant women; six women with fetuses who were of Rh(D) negative phenotype, 19
      women with fetuses who were Rh(D) positive and received no treatment and, seven
      women who were treated with i.v.IG because they bore anemic, Rh(D) positive
      fetuses. RESULTS: Fetuses with a Rh(D) negative phenotype expressed an increase
      in fetal/maternal anti-D concentration ratios from 10 to 55% between 25 and 31
      gestational weeks, while Rh(D) positive fetuses without i.v.IG treatment had
      stable values at the 10% level between 24 and 35 gestational weeks. During i.v.IG
      treatment of the mothers, Rh(D) positive fetuses showed an increase in ratio from
      10 to 30% between 26 and 34 gestational weeks. There was a statistically
      significant (p<0.001) difference between regression results of the three groups.
      CONCLUSIONS: Fetal anti-D is consumed in the hemolytic process and the
      consumption can be modulated by i.v.IG given to the mother.

PMID- 9654171
TI  - Placental isoferritin in gestational diabetes mellitus.
AB  - BACKGROUND: Serum placental isoferritin, an immunosuppressive cytokine like
      protein, was found to be elevated in type I diabetes at diagnosis and low in high
      risk pregnant women. Further to this observation, the possible role of this
      placental product was assessed in pregnant women with gestational diabetes
      mellitus. METHODS: A comparative study. One hundred and seventy-four pregnant
      women were included in the study: 28 were diagnosed as gestational diabetes
      mellitus and 146 were normal controls. MAIN OUTCOME MEASURES: Samples for serum
      placental ferritin were measured in the second and third trimesters of pregnancy.
      RESULTS: Serum placental isoferritin values were significantly lower in the
      second trimester of pregnancy in the gestational diabetes mellitus group (9.4+/
      2.6 U/ml) as compared with the control group (21.5+/-2.2 U/ml, p=0.0001), and
      were also significantly lower in the third trimester (3.7+/-1.9 vs. 19+/-2.6
      U/ml, respectively, p=0.00001). CONCLUSIONS: Low serum PLF values detected in
      gestational diabetes mellitus may reflect placental function and be related to
      insulin treatment.

PMID- 9654172
TI  - Interleukin-1alpha, interleukin-6 and interleukin-8 in cervico/vaginal secretion
      for screening of preterm birth in twin gestation.
AB  - BACKGROUND: The purpose was to determine the prognostic value of interleukin (IL)
      1-alpha, IL-6 and IL-8 in cervico/vaginal secretion for preterm birth (<37 weeks
      of gestation) in twin pregnancies. METHODS: The study included screening of 121
      women with twin pregnancies with sampling at 24, 26, 28, 30, 32 and 34 weeks of
      gestation. IL-1alpha, IL-6 and IL-8 was analyzed with ELISA immunoassays. The
      detection limit was 30 pg/mL for IL-1 and IL-8 and 40 pg/mL for IL-6. Vaginal
      fluid was smeared and dried for later evaluation of bacterial vaginosis (presence
      of clue cells). RESULTS: Spontaneous preterm birth occurred in 36 women and 65
      women were delivered at term. IL-8 was significantly higher (p=0.03) in samples
      from women delivered preterm (median 3.72 ng/g mucus, range <0.07-220.00)
      compared with samples from women delivered at term (median 3.03 ng/g mucus, range
      <0.08-378.60). At 28 weeks of gestation, IL-8 (cut off 1.75 ng/g mucus) was
      associated with preterm delivery (relative risk 2.2, CI 95% 1.1-4.5) with a
      sensitivity, specificity, positive and negative predictive value of 78.8, 45.8,
      44.8 and 79.4%, respectively. The levels of IL-1alpha and IL-6 were not
      significantly associated with preterm birth. Bacterial vaginosis was found in
      47/541 (8.7%) samples analyzed. The levels of IL-1alpha and IL-8 were
      significantly higher in samples positive for bacterial vaginosis than in negative
      samples (p<0.0001 and p<0.01, respectively). There was no significant association
      between the level of IL-6 and bacterial vaginosis. CONCLUSIONS: IL-8, but not IL
      1alpha and IL-6, was associated with preterm delivery but the relationship was
      too weak to be of predictive value for preterm birth in twin pregnancies. IL
      1alpha and IL-8, but not IL-6, were associated with bacterial vaginosis.

PMID- 9654173
TI  - The relationship between amniotic fluid interleukin-6 concentration and
      histologic evidence of chorioamnionitis.
AB  - BACKGROUND: Chorioamnionitis is considered to be one of the important causes of
      preterm labor. To investigate the relationship between inflammatory cytokines in
      amniotic fluid and the histologic evidence of chorioamnionitis, we studied
      amniotic fluid interleukin-6 (IL-6) levels in patients with preterm labor.
      METHODS: Between 1993 and 1996, we obtained amniotic fluid by amniocentesis from
      110 patients before 32 weeks of gestation who had preterm labor on admission. We
      measured IL-6 levels in the amniotic fluid with an ELISA method. Histologic
      examination of placentae and fetal membranes after delivery was evaluated. As
      controls, we measured IL-6 levels in the amniotic fluid of 37 patients without
      preterm labor. Seventy-eight patients delivered after 35 weeks of gestation, and
      32 patients delivered before 34 weeks of gestation. Analysis was conducted using
      Mann-Whitney U test and Scheffe's multiple comparison test. RESULTS: Amniotic
      fluid IL-6 levels in patients delivering before 34 weeks were significantly
      higher than those in patients delivering after 35 weeks (p<0.01). IL-6 levels in
      the amniotic fluid were significantly different among control patients, patients
      without chorioamnionitis and those with histologic stages I, II and III which
      means subchorionic intervillositis, chorionitis and amnionitis, respectively
      (controls vs patients with stage I, II, III: p<0.001, patients without
      chorioamnionitis vs those with stage II, III, stage I vs II, stage II vs III:
      p<0.01). The IL-6 concentration in the amniotic fluid associated with histologic
      stages II or III was above 3500 pg/ml (sensitivity: 87.5%, specificity: 89.5%).
      CONCLUSIONS: Our findings indicate that amniotic fluid IL-6 may have a sensitive
      diagnostic and prognostic value in the management of preterm labor and is an
      index of the severity of chorioamnionitis during pregnancy.

PMID- 9654174
TI  - A comparison of Caucasian and Southeast Asian Hmong uterine fundal height during
      pregnancy.
AB  - BACKGROUND: Fundal height measurement is a standard clinical assessment tool used
      in prenatal care. This study compared the fundal heights growth curves of two
      ethnically distinct groups of pregnant women. We were motivated by our clinical
      experience with one group where fundal heights seemed 'small for date' and by the
      reluctance of this group to undergo further testing, especially ultrasound.
      METHODS: A prospective cohort study compared the fundal heights growth curve of
      48 Caucasian and 40 Hmong women from two clinics in central Wisconsin (USA).
      RESULTS: Southeast Asian Hmong women were found to have a slower rate of fundal
      height growth than Caucasian women (significantly different average slopes of .88
      vs. .95, respectively). An expectation of linear growth appeared more valid for
      Caucasian than Hmong women. At 40 weeks, regression based estimates overestimated
      the Caucasian sample by 1.3 weeks and the Hmong sample by 2.7 weeks. ANCOVA
      procedures remained significant while controlling for group differences in
      height. Fundal height measurements were moderately predictive of birth weight for
      the Hmong sample but not the Caucasian sample (multiple r=.39). CONCLUSIONS:
      Considerable differences emerged between fundal height measures for the Hmong and
      Caucasian samples. The improved ability to differentiate groups following control
      of variance due to height as well as the ability to predict birth weight from
      fundal height curve in the Hmong group argue for value of normative development
      using more homogeneous groups. Clinicians should consider the applicability of
      fundal height norms to their clinical populations and may be able to have more
      confidence in using fundal height as an evaluative tool with more appropriate
      norms.

PMID- 9654175
TI  - Impact of reverse end-diastolic flow velocity in umbilical artery on pregnancy
      outcome after the 28th gestational week.
AB  - BACKGROUND: The aim of this study was to discuss pregnancy outcome in
      chromosomally and structurally normal fetuses having reverse end-diastolic flow
      velocity (REDFV) on Doppler umbilical artery velocimetry (DUAV) in the third
      trimester. METHODS: DUAV was performed in the high risk pregnancy antepartum
      fetal surveillance. We excluded gestational age less than 28 weeks, multiple
      pregnancies, and chromosomal or congenital anomalies. Thirty cases were
      categorized as having REDFV The pregnancy outcome was investigated in these
      cases. RESULTS: There were three stillbirths and 12 neonatal deaths, resulting in
      a perinatal mortality rate of 50%. Twenty-eight patients (93.3%) had
      complications with preeclampsia (20 of severe degree and eight moderate).
      Cesarean section was performed on 24 patients (80%) due to acute fetal distress.
      The mean gestational age at delivery was 31.8+/-3.2 weeks. The mean diagnosis-to
      delivery interval was 10+/-8.2 hours. The average birth weight was 970+/-270 gm,
      28 (93.3%) were found to be below the 10th percentile of ideal birth weight. An
      umbilical artery pH less than 7.2 at delivery was found in 12 of 18 examined
      cases (66.7%). Twelve out of 15 placentae (80%) showed significant infarcts on
      pathological examination. All newborns (100%) needed admission to the neonatal
      intensive care unit. CONCLUSIONS: REDFV on DUAV represents an ominous and severe
      fetal condition with an adverse pregnancy outcome, especially in conditions
      associated with preeclampsia and/or intrauterine growth retardation. Intensive
      and frequent surveillance and aggressive management at the appropriate time would
      improve perinatal outcome.

PMID- 9654176
TI  - Pregnancy in HIV-infected women. Counseling and care--12 years' experiences and
      results.
AB  - BACKGROUND: A specialized antenatal care unit was set up for counseling and care
      of HIV-infected pregnant women. The team consisted of gynecologists, a midwife, a
      social worker and pediatricians. METHODS: The women were referred from
      departments of infectious diseases, venereology or institutions for drug addicts,
      antenatal care units and abortion clinics, or applied themselves. Women
      identified in the pregnancy HIV screening program were informed primarily by the
      team. The women were counseled along with their partners and cared for during
      abortion or the antenatal period, delivery and post partum. Contraceptive
      services were offered and psychosocial support was given. RESULTS: Between April
      1985 and March 1997, 95 HIV-infected women with 122 pregnancies attended. Twenty
      one per cent were or had been drug users, 2% had been infected by transfused
      blood and 77% were classified as having been sexually infected, two thirds of
      whom were Africans. The mean age was 27.8 years. In 54 of 93 pregnancies (58%) in
      which the woman could make an informed decision, she elected abortion -- in 37
      cases for HIV related reasons. Significantly more women with an uninfected steady
      partner, compared to women without a steady partner, chose to continue the
      pregnancy, as did women in a relatively stable social situation. Of the partners,
      68 were HIV-negative, 36 HIV-positive and 18 not tested. No severe HIV-related
      complications occurred during pregnancy. Seven of 40 (18%) children with a known
      infection status were infected. During the course of follow-up, nine mothers, two
      fathers and three children have died. Seventeen children were at risk of being
      orphaned, and another five were placed in foster care. CONCLUSION: Although it is
      possible to reduce mother-to-infant transmission by zidovudine therapy, the
      negative consequences of HIV and childbearing are still substantial. Therefore
      HIV screening during pregnancy and pre-pregnancy counseling are important issues
      for the health care system.

PMID- 9654177
TI  - Fear of childbirth during pregnancy may increase the risk of emergency cesarean
      section.
AB  - BACKGROUND: The purpose of our study was to elucidate the association between
      fear of childbirth, general anxiety, and stress coping during the third trimester
      of pregnancy, and a subsequent delivery by emergency cesarean section. METHODS:
      In a case-control study, 1,981 Swedish-speaking women completed three self
      assessment questionnaires at 32 weeks' gestation. Ninety-seven of these women
      were delivered by emergency cesarean section. Fear of childbirth, general anxiety
      and the stress coping ability of these 97 cases were compared with the same
      features in 194 controls, matched for age and parity. RESULTS: Women,
      subsequently delivered by emergency cesarean section, reported a greater anxiety
      and a poorer stress coping ability, and, most obviously, a greater fear of
      childbirth at 32 weeks' gestation. After elimination of possible confounders, the
      odds ratio for emergency cesarean section was examined for women whose scores
      were above various cut-off points according to the fear of childbirth measuring
      instrument. For women with a serious fear of childbirth the odds ratio was 3.0
      (95% confidence interval 1.4 to 6.6), and the population attributable risk 0.167.
      CONCLUSION: Fear of childbirth during the third trimester of pregnancy may
      increase the risk of subsequent emergency cesarean section.

PMID- 9654178
TI  - Intrauterine irrigation with prostaglandin F2-alpha for management of severe
      postpartum hemorrhage.
AB  - BACKGROUND: Severe postpartum hemorrhage is a significant contributor to maternal
      morbidity and mortality. The use of prostaglandin F2-alpha to control severe
      postpartum hemorrhage may avert surgery for the control of bleeding. METHODS:
      After ruling out the possibility of genital tract injuries, 18 patients with
      severe postpartum hemorrhage caused by uterine atony were enrolled in the study.
      None of the patients responded to treatment with oxytocin, methylergonovine, or
      uterine massage. A Foley catheter was introduced into the uterine cavity and the
      balloon was inflated with 5 ml sterile saline solution. The catheter was
      connected to an infusion line of 500 ml saline solution containing 20 mg
      prostaglandin F2-alpha. The solution was infused at a rate of 3-4 ml/minute for
      the first 10 min, and then reduced to 1 ml/minute for a period of 12 24 hours.
      RESULTS: In 17 patients (94.4%) bleeding ceased within several minutes of
      initiation of intrauterine prostaglandin F2-alpha infusion, the uterus was firmly
      contracted and uterine bleeding did not recur. In one patient with placenta
      increta bleeding continued and hysterectomy was performed. None of the patients
      had any side effects. CONCLUSIONS: Intrauterine irrigation with low
      concentrations of prostaglandin F2-alpha is a simple, rapid and effective
      treatment for severe postpartum hemorrhage and facilitates constant and
      continuous hemostasis. Moreover, the minute dosage used eludes potentially
      complicating side effects.

PMID- 9654179
TI  - Premenstrual syndrome: comparison between different methods to diagnose cyclicity
      using daily symptom ratings.
AB  - BACKGROUND: In the diagnosis of premenstrual syndrome (PMS) the technique of
      daily prospective symptom ratings is often used. Several methods of assessing
      cyclicity, based on the daily prospective symptom ratings, have been presented in
      the literature. In this paper we compare four different methods to assess
      cyclicity. METHODS: Eighty consecutive patients seeking help for PMS at the
      Department of Gynecology completed daily symptom ratings using a visual analogue
      scale (VAS) during one menstrual cycle. They also made an Eysenck Personality
      Inventory (EPI) and a thorough case history was taken regarding earlier
      psychiatric case history. The methods compared were: a) the nonparametric Mann
      Whitney U-test, b) effect size, c) Run-test and d) a 30% change in symptom degree
      between the follicular and the luteal phase calculated in two different ways.
      RESULTS: There was good agreement in the number of cyclic and non-cyclic patients
      between the different diagnostic methods used with exception of the 30% of change
      methods as the criteria for cyclicity. Here the number of non-cyclic patients
      became higher and lower, respectively, than with the other methods. The
      correlation between the number of symptoms for each patient showing cyclicity was
      high in all tests. When comparing the median neuroticism score of the EPI-N
      inventory the non-parametric, the Run-test and the effect size showed significant
      differences between the non-cyclic group and the group of patients with pure PMS,
      but not the 30%-change methods. Frequency of patients with psychiatric history
      showed similar results. CONCLUSIONS: Three of the methods used seem to identify
      the same patients as having or not having cyclical changes and probably also then
      finding the same biological and/or psychological factor being responsible for the
      cyclicity. There were, however, some differences in outcome of validity testing
      and the 30%-change methods seem less valid than the other three methods. Due to
      its simplicity and theoretical/statistical advances the Run-test seems most
      preferable.

PMID- 9654180
TI  - CO2 laser conization for cervical intraepithelial neoplasia grade II-III:
      complications and efficacy.
AB  - AIMS: To examine per- and postoperative complication rates and efficacy of laser
      conization in the treatment of cervical intraepithelial neoplasia (CIN) grade II
      III. MATERIAL AND METHODS: Eligible for analyses were all women treated with
      their first laser conization because of CIN II-III during the time-period January
      1, 1983 to December 31, 1992. The study population comprises 1081 women who were
      permanent residents of one Norwegian county (Sor-Trondelag). All analyses were
      performed in SPSS applying chi-square for trend, Mann-Whitney test, survival
      analyses and logistic regression. RESULTS: In total 86 women (8.0%) were observed
      with one or two (4:86) complications. Bleeding was most frequent (n = 66)
      followed by symptomatic cervical stenosis (n = 18). Most bleeding complications
      (74.2%) occurred one to two weeks postoperatively. Both bleeding complications
      and the occurrence of cervical stenosis were associated with cone height. Three
      emergency hysterectomies, two for bleeding and one for bladder perforation, were
      performed. Persistent disease was diagnosed in 1.9% (20:1053) of the women. All
      women with persistent disease were diagnosed among those with CIN III. Persistent
      disease was more than 20 times more common among women with disease-involved
      resection margins compared to those with free resection margins. CONCLUSIONS: Our
      evaluation of ten years' consistent use of conization by CO2 laser in the
      treatment of CIN II-III in an unselected population showed a low overall
      complication rate (8%) and very high efficacy (CIN II 100%, CIN III 98.1%) of the
      treatment.

PMID- 9654181
TI  - Bleeding symptoms and subsequent risk of gynecological and other cancers.
AB  - BACKGROUND: The purpose of our study was to find out whether bleeding symptoms
      are predictive factors of subsequent gynecological or urinary cancers among women
      screened negative. METHODS: The data stemmed from the Finnish Mass Screening
      Registry, and were linked to the National Cancer Registry: 37,596 screening
      negative women in the nationwide population-based mass screening program for
      cervical cancer were classified by their bleeding symptom (bloody discharge,
      coital bleeding, irregular bleeding, postmenopausal bleeding) at the time of
      screening (1985-1990) and followed up (1985-1994) in order to assess the
      subsequent risk of cancer. RESULTS: Bleeding symptoms with prevalence of 5.9%
      were more likely to be signs of preinvasive than invasive cervical cancer with
      the exception of coital bleeding, nevertheless relative risk of cervical cancer
      (SIR 1.1, 95% CI 0.8-1.4) was not significantly increased during the total follow
      up of maximum 10 years. Women with any bleeding symptom had increased risk of
      cancer of the corpus uteri (SIR 2.1, 95% CI 1.6-2.6), postmenopausal bleeding was
      the strongest symptom (RR 3.6, 95% CI 2.0-6.0). None of the bleeding symptoms
      increased subsequent risk of ovarian, vaginal or vulvar carcinoma. The risk of
      kidney cancer was increased (SIR 1.7, 95% CI 1.0-2.6). CONCLUSIONS: The
      prevalence of bleeding symptoms was small and relative risks for cancers were low
      for them to be suitable as predictive factors of cancer neither in clinical
      practice nor for public health purposes, e.g. in developing selective screening
      based on this high risk group. Only 34 gynecological cancers during 220,000
      person-years in women with bleeding symptoms were attributable to bleeding.
      Relative risks remained increased only for a short time after screening.
      Therefore, short term surveillance is important, but due to the fact that
      relative risks approached unity during the follow-up, reassurance of a woman that
      she is cancer-free should be emphasized more in the long term after the bleeding
      symptoms.

PMID- 9654182
TI  - Exposure to angiotensin-converting enzyme inhibitors during first trimester: is
      it safe to fetus?

PMID- 9654183
TI  - Psychosocial factors in recurrent miscarriages.

PMID- 9654184
TI  - Pregnancy in heart and heart-lung transplant recipients.

PMID- 9654185
TI  - Management of a pregnancy complicated by the May-Hegglin anomaly.

PMID- 9654186
TI  - Uterine arteriovenous malformation as a cause of immediate postpartum hemorrhage.

PMID- 9654187
TI  - Hysteroscopic metroplasty under laparoscopic ultrasound guidance.

PMID- 9654188
TI  - Stillbirths and rate of neonatal deaths in 76,761 postterm pregnancies in Sweden,
      1982-1991; a register study.

PMID- 9654189
TI  - Expression of membrane-type matrix metalloproteinase-1 in human pancreatic
      adenocarcinomas.
AB  - The expression of a new type of matrix metalloproteinase, membrane-type matrix
      metalloproteinase-1 (MT-MMP-1), was examined in 24 cases of primary pancreatic
      adenocarcinomas and 9 cases of secondary liver tumors derived from pancreatic
      adenocarcinomas, using a non-radioactive in situ hybridization and
      immunohistochemical methods. Out of 24 cases of primary pancreatic
      adenocarcinomas, 18 showed positive expression of MT-MMP-1 transcripts in cancer
      cells and 20 of 24 showed positive expression in the tumor stromal cells. The
      immunoreactivity of the gene products for MT-MMP-1 was demonstrated to be almost
      the same, as shown by in situ hybridization in these 24 cases. In particular,
      both the staining intensity for MT-MMP-1 transcripts and the immunoreactivity of
      the gene products in the tumor stromal cells of mucinous cystadenocarcinomas were
      significantly weaker than those of common-type ductal adenocarcinomas among the
      24 cases. All of the 9 cases of secondary liver tumors derived from pancreatic
      adenocarcinomas showed positive expression for MT-MMP- transcripts but less
      immunoreactivity for the gene products. These results suggest that MT-MMP-1 is
      transcribed and translated in both cancer cells and the tumor stromal cells in
      human pancreatic adenocarcinomas. Furthermore, considering that common-type
      ductal adenocarcinoma of the pancreas usually shows a strong desmoplastic
      reaction, while mucinous cystadenocarcinoma typically does not, MT-MMP-1
      expressed in the tumor stromal cells of common-type adenocarcinomas may be
      involved in processes leading to the desmoplastic reaction.

PMID- 9654190
TI  - Inability of galactoside-specific mistletoe lectin to inhibit N-methyl-N
      nitrosourea-induced tumor development in the urinary bladder of rats and to
      mediate a local cellular immune response after long-term administration.
AB  - Extracts from mistletoe (Viscum album L.) are assumed to exert an antineoplastic
      activity through their toxicity at high doses or by immunomodulation by nanogram
      quantities of a lectin. They are used as an unconventional therapy modality in
      the management of a wide range of cancer diseases, although no anticancer
      potential has yet been demonstrated. This prompted us to study the effect of
      galactoside-specific lectin (VAA)--a major protein constituent of mistletoe with
      immunomodulatory properties--on chemically induced tumor development in the
      urinary bladder of rats and on the local cellular immune response after long-term
      administration. To induce urothelial neoplasms N-methyl-N-nitrosourea (MNU) was
      administered in a single intravesical dose (7.5 mg/kg body weight). Highly
      purified VAA was given subcutaneously at its immunomodulatory dose (1 ng/kg body
      weight) twice a week over the total experimental period of 15 months. The
      incidences of epithelial bladder tumors were 25.0% following administration of
      MNU alone and 22.9% in the rats additionally receiving VAA, which proved not to
      be significantly different (P = 0.81). Quantitative immunohistochemistry
      analyzing a panel of immune cell types, including T lymphocytes, T helper/inducer
      cells (CD4), T suppressor/cytotoxic cells (CD8), T cells positive for interleukin
      2 receptor (CD25), B lymphocytes and plasma cells, macrophages, natural killer
      cells, granulocytes and all leukocytes expressing the leukocyte common antigen
      (CD45), yielded no evidence for the ability of VAA to stimulate a substantial
      cellular immunological reaction in the wall of the normal urinary bladder or
      during urothelial carcinogenesis. In conclusion, the current experimental
      findings provide no support at all that the galactoside-specific mistletoe lectin
      is capable of inhibiting chemically induced bladder carcinogenesis and triggering
      a local cellular immune response after prolonged application. It thus seems
      highly improbable that commercial mistletoe preparations or VAA will be effective
      in the management of human bladder cancer by a cell-mediated immunological
      mechanism.

PMID- 9654191
TI  - Chemoattractive effect on the effector cells of the supernatants from melanoma
      cells transfected with the interleukin-2 (IL-2), IL-4 or IL-6 gene.
AB  - By using the Boyden chamber system, the chemoattractive activity of the
      supernatants from the B16 melanoma cells transfected with the interleukin-2 (IL
      2), IL-4 or IL-6 gene was investigated. We found that supernatants from IL-2- or
      IL-6-gene-transfected B16 melanoma cells showed chemoattractive activity on
      natural killer (NK) cells, CD4+ T cells and CD8+ T cells, while the supernatants
      from IL-4-gene-transfected B16 melanoma cells showed chemotactic activity on
      macrophages but not on NK cells and T cells. Further, the chemoattractive
      activity of the supernatants from cytokine-gene-transfected B16 cells might be
      the direct effects of the cytokine that they have been engineered to secrete.
      These results indicate that reduced tumorigenicity and increased immunogenicity
      of cytokine-gene-transfected B16 cells may be attributed to the direct
      recruitment of immune effector cells by the secreted cytokine, which plays an
      important role in the induction of the local antitumor immunity.

PMID- 9654192
TI  - Differentiation, proliferation and apoptosis levels in human leiomyoma and
      leiomyosarcoma.
AB  - A comparative analysis of the differentiation pattern, the proliferative
      behaviour, and the level of apoptosis between human benign and malignant
      neoplasms of smooth-muscle (SM) tissue is lacking. The clinical,
      histopathological, immunochemical, and immunocytochemical features of leiomyomas
      (LM) and leiomyosarcomas (LMS) were investigated by a panel of monoclonal
      antibodies specific for some differentiation markers of SM tissue (SM myosin and
      alpha-actin, desmin, and SM22) and for markers of non-muscle tissue (vimentin and
      non-muscle myosin). Proliferating normal and neoplastic cells were identified by
      proliferating-cell nuclear antigen (PCNA)/Ki67 immunostainings and the apoptotic
      cells were revealed by means of the terminal-deoxynucleotidyltransferase-mediated
      dUTP nick-end labelling technique. Gel electrophoresis and Western blotting,
      performed with anti-(SM1/SM2 myosin isoform) antibody, indicated quantitative
      differences between LMS and LM, which mirrored higher positive to negative
      nuclear ratios for PCNA, Ki67 and apoptosis in malignant as opposed to benign
      neoplasms. With LM, however, a similar SM1 to SM2 ratio could be associated with
      different proliferation levels. Uterine, gastric and intestinal LMS displayed
      specific patterns of SM1/SM2 and/or non-muscle myosin expression that were not
      paralleled by different levels of proliferation/apoptosis. While the level of
      PCNA/Ki67 correlated with the level of apoptosis in normal SM tissues and LM,
      that of LMS did not. In vivo at the cellular level, LM and uterine LMS displayed
      a near-uniform SM tissue differentiation, whereas the other LMS displayed a
      lesser or a heterogeneous immunoreactivity. In vitro, cultured LMS cells showed a
      limited and peculiar expression of SM myosin. In conclusion, there is no
      reciprocal relationship between degree of differentiation and the level of
      proliferation, as exemplified by the finding that the less differentiated
      intestinal LMS displays the lowest proliferative behaviour and that the
      relatively more differentiated gastric LMS/metastasis is more proliferative.

PMID- 9654194
TI  - Impaired granulocytic function in patients with acute leukaemia: only partial
      normalisation after successful remission-inducing treatment.
AB  - In vivo chemotaxis and phagocytic activity of polymorphonuclear neutrophils (PMN)
      were evaluated in 20 patients with acute myeloid leukaemia (AML), and in 10
      patients with acute lymphoblastic leukaemia (ALL). For comparison, 20 healthy
      individuals were investigated. A skin-chamber technique and a phagocytosis test
      were used to quantify the neutrophil functions. The local leucocyte mobilisation
      in the skin-chamber was significantly lower in untreated patients with AML and
      ALL than in healthy individuals (P < 0.05). Patients with acute leukaemia in
      remission showed an increase in chemotactic parameters though they remained below
      normal levels. The phagocytosis index (PI) of peripheral blood PMN was lower than
      30% (normal individuals: 60%) in untreated AML and ALL; this difference was
      significant (P < 0.05). The PI of peripheral blood PMN in patients with acute
      leukaemia in remission returned to the normal level. Investigation of
      granulocytic function in patients with acute leukaemia in remission may reveal
      evidence for reduced protection by these cells against infections and lead to
      adequate therapy.

PMID- 9654193
TI  - Does chemotherapy-induced leukopenia predict a response in small-cell lung
      cancer?
AB  - The correlation between chemotherapy-induced toxicity and treatment outcome in
      cancer patients has not been studied thoroughly. Our aim was to evaluate whether
      there is any relationship between chemotherapy-induced leukopenia and response to
      treatment in small-cell lung cancer (SCLC). Data derived from records of 228
      patients treated within two prospective multicentre phase II studies were
      analysed. In the first study (101 patients) chemotherapy included vincristine,
      epirubicin and cyclophosphamide and, in the second (127 patients),
      cyclophosphamide, etoposide and epirubicin; both regimens were given every 3
      weeks. In the present analysis, the correlation between treatment outcome
      (response rate and survival) and highest scores of leukopenia within the first
      two and up to the fourth chemotherapy cycle, respectively, was evaluated. The
      objective response rate for the entire group was 66%; 53% in patients whose white
      blood cells remained normal and 85% in those who developed leukopenia within the
      first two cycles (P = 0.000). In multifactorial analysis, also including other
      treatment- and patient-related factors, independent correlation with response to
      chemotherapy was found for leukopenia (P = 0.001), chemotherapy regimen (P =
      0.002) and the combined relative dose intensity (P = 0.018), but not for patient
      sex, age, performance status, pre-study weight loss, extent of disease and
      initial white blood cell count. Leukopenia within the first two cycles of
      chemotherapy was not correlated with survival, whereas such correlation for
      leukopenia occurring up to the fourth cycle was at the borderline level (P =
      0.06). These findings suggest a relationship between chemotherapy-induced
      leukopenia and tumour response in SCLC.

PMID- 9654195
TI  - Increased prosomal proteins in breast cancer cells and in neighboring normal
      cells in Parsi and non-Parsi populations.
AB  - Monoclonal antibodies were raised against the prosomal proteins p27K, p29K and
      the prosome-like protein p21K (PLP) from normal breast glandular cells and from
      benign and malignant tumors. They were used to clarify the involvement of
      prosomes in tumorigenesis of human breast cells. Immunostaining showed the
      distribution of prosomes in the cytoplasm and nuclei of cells from European
      normal women (EN) and Parsi (P) and non-Parsi (NP) benign (B) and malignant (M)
      tissues. The flow-cytometry studies showed an increased mean percentage of
      labeled cells, particularly with anti-p27K prosomal protein mAb, in malignant
      tissue from NP compared to EN. The p21K data indicated an increase in the number
      of cells labeled by flow-cytometry studies in all groups compared to EN, while
      p29K-expressing cells were more abundant in NPN, PB, PM and NPM. Intergroup
      comparison showed that the mean percentage of cells labeled with anti-p27K and
      anti-p29K was significantly higher in PB than in NPB, as seen by flow cytometry,
      whereas there was a higher production or accumulation of the p21K (PLP) prosomal
      protein in NPM than in PM, as seen by immunostaining. By comparison with EN,
      there were also significantly more normal cells containing the three antigens in
      the apparently normal tissue in the neighborhood of the tumor in NPM, and more
      cells containing p21K in PM patients than in EN. As prosomes are involved in the
      cell differentiation and in the cell cycle control, the changes observed in
      breast tissues may be related to oncogenic processes. Furthermore, the modified
      subunit pattern of prosomes in cancer and, possibly, pre-cancer tissue may be of
      interest for diagnosis purposes.

PMID- 9654196
TI  - Complete response of a primary cutaneous T-cell-rich B cell lymphoma treated with
      interferon alpha2a.
AB  - Primary B cell lymphomas of the skin are rare disorders and therapy is not yet
      standardized. A 45-year-old male patient presented 4 years after surgical removal
      of a subcutaneous tumour of the leg. On examination a reddish nodular tumour was
      found in the same region. The biopsy revealed a T-cell-rich primary B cell
      lymphoma of the skin. Interferon alpha2a was given perilesionally at a dosage of
      9 MU three times a week. The treatment was well tolerated, had no severe side
      effects and induced a complete remission, both clinically and histologically,
      during a 12-months course.

PMID- 9654197
TI  - Correlation between Waardenburg syndrome phenotype and genotype in a population
      of individuals with identified PAX3 mutations.
AB  - Waardenburg syndrome (WS) type 1 is an autosomal dominant disorder characterized
      by sensorineural hearing loss, pigmentary abnormalities of the eye, hair, and
      skin, and dystopia canthorum. The phenotype is variable and affected individuals
      may exhibit only one or a combination of several of the associated features. To
      assess the relationship between phenotype and gene defect, clinical and genotype
      data on 48 families (271 WS individuals) collected by members of the Waardenburg
      Consortium were pooled. Forty-two unique mutations in the PAX3 gene, previously
      identified in these families, were grouped in five mutation categories: amino
      acid (AA) substitution in the paired domain, AA substitution in the homeodomain,
      deletion of the Ser-Thr-Pro-rich region, deletion of the homeodomain and the Ser
      Thr-Pro-rich region, and deletion of the entire gene. These mutation classes are
      based on the structure of the PAX3 gene and were chosen to group mutations
      predicted to have similar defects in the gene product. Association between
      mutation class and the presence of hearing loss, eye pigment abnormality, skin
      hypopigmentation, or white forelock was evaluated using generalized estimating
      equations, which allowed for incorporation of a correlation structure that
      accounts for potential similarity among members of the same family. Odds for the
      presence of eye pigment abnormality, white forelock, and skin hypopigmentation
      were 2, 8, and 5 times greater, respectively, for individuals with deletions of
      the homeodomain and the Pro-Ser-Thr-rich region compared to individuals with an
      AA substitution in the homeodomain. Odds ratios that differ significantly from
      1.0 for these traits may indicate that the gene products resulting from different
      classes of mutations act differently in the expression of WS. Although a
      suggestive association was detected for hearing loss with an odds ratio of 2.6
      for AA substitution in the paired domain compared with AA substitution in the
      homeodomain, this odds ratio did not differ significantly from 1.0.

PMID- 9654198
TI  - A study of females with deletions of the short arm of the X chromosome.
AB  - We have undertaken a clinical and molecular study of 25 females with deletions of
      the short arm of the X chromosome. We have determined the deletion breakpoints,
      the parental origin and the activation status of the deleted X chromosomes.
      Genotype-phenotype correlations suggest that the presence of a single copy of the
      DFFRX gene, previously postulated as a gene involved in the ovarian failure seen
      in Turner syndrome, may be compatible with normal ovarian function, and that
      there may be a gene for Turner-like features located in distal Xp22.3.

PMID- 9654199
TI  - A haplotype and linkage disequilibrium analysis of the hereditary hemochromatosis
      gene region.
AB  - Hereditary hemochromatosis is a recessive disease of iron metabolism widely
      distributed among people of European descent. Most patients have inherited the
      causative mutation from a single ancestor. In the course of cloning the
      hemochromatosis gene, genotypes were generated for these samples at 43
      microsatellite repeat markers that span the 6.5-Mb hemochromatosis gene region.
      The data used to reconstruct the ancestral haplotype across the hemochromatosis
      gene region are presented in this paper. Portions of the ancestral haplotype were
      present on 85% of patient chromosomes in this sample and ranged in size from
      approximately 500 kb to greater than 6.5 Mb. Only one marker, D6S2239, was
      identical by descent on all of the patient chromosomes containing the ancestral
      mutation. In contrast, only 3 of the 128 control chromosomes, or 2.3%, carried
      the ancestral mutation and the surrounding ancestral haplotype. To test new
      methods for gene finding using linkage disequilibrium we analyzed the genotypic
      data with a multilocus maximum likelihood method (DISMULT) and a single point
      method (DISLAMB), both written to analyze data generated from multi-allelic
      markers. The maximum value from DISLAMB analysis occurred at marker D6S2239,
      which is less than 20 kb from the hemochromatosis gene HFE, consistent with the
      haplotype analysis. The peak of the multi-point analysis was 700 kb from HFE,
      possibly due to the nonuniform recombination rates within this large region. The
      recombination rate appears to be lower than expected centromeric of the HFE gene.

PMID- 9654200
TI  - Lack of association between human longevity and genetic polymorphisms in drug
      metabolizing enzymes at the NAT2, GSTM1 and CYP2D6 loci.
AB  - In the present study, the possible role of genetic polymorphism of three drug
      metabolizing enzymes, debrisoquine/sparteine hydroxylase (CYP2D6), glutathione S
      transferase mu (GSTM1), and N-acetyltransferase (NAT2), as a putative genetic
      component of human longevity, was explored. A total of 817 DNA samples from a
      centenarian and a control (20-70 years) population was subjected to PCR-coupled
      RFLP methods. Subjects were genotyped for the CYP2D6*3 (A2637 deletion) and
      CYP2D6*4 (G1934A transition) alleles, for four mutations of NAT2 [namely, NAT2*5A
      (C481T), NAT2*6A (G590A), NAT2*7A (G857A), and NAT2*14A (G191A)], and for the
      presence or absence of GSTM1 gene deletion. No significant difference was found
      at these three loci between centenarian and control subjects with respect to
      allelic variant frequencies, genotype distributions or predicted phenotypes
      deduced from genotype combinations. By comparing the distribution of combined
      genotypes for the polymorphisms tested at the CYP2D6, NAT2, and GSTM1 loci, none
      of the predicted phenotypes concerning debrisoquine hydroxylase extensive
      metabolizer or poor-metabolizer phenotypes, slow or fast N-acetylation
      capacities, and active or defective glutathione S-transferase, could be
      correlated with human longevity, alone or in combination.

PMID- 9654201
TI  - Dopamine beta-hydroxylase: two polymorphisms in linkage disequilibrium at the
      structural gene DBH associate with biochemical phenotypic variation.
AB  - Levels of the enzyme dopamine beta-hydroxylase (DbetaH) in the plasma and
      cerebrospinal fluid (CSF) are closely related biochemical phenotypes. Both are
      under strong genetic control. Linkage and association studies suggest the
      structural gene encoding DbetaH (locus name, DBH) is a major locus influencing
      plasma activity of DbetaH. This study examined relationships of DBH genotype
      determined at two polymorphic sites (a previously described GT repeat, referred
      to as the DBH STR and a single-base substitution at the 3' end of DBH exon 2,
      named DBH*444 g/a), to CSF levels of DbetaH protein in European-American
      schizophrenic patients, and to plasma DbetaH activity in European-American
      patients with mood or anxiety disorders. We also investigated linkage
      disequilibrium (LD) between the polymorphisms in the pooled samples from those
      European-American subjects (n=104). Alleles of DBH*444 g/a were associated with
      differences in mean values of CSF DbetaH levels. Alleles at both polymorphisms
      were associated with plasma DbetaH activity. Significant LD was observed between
      respective alleles with similar apparent influence on biochemical phenotype.
      Thus, allele A3 of the DBH STR was in positive LD with DBH*444a, and both alleles
      were associated with lower plasma DbetaH activity. DBH STR allele A4 was in
      positive LD with DBH*444 g, and both alleles were associated with higher plasma
      DbetaH activity. The results confirm that DBH is a major quantitative trait locus
      for plasma DbetaH activity, and provide the first direct evidence that DBH also
      influences CSF DbetaH levels. Both polymorphisms examined in this study appear to
      be in LD with one or more functional polymorphisms that mediate the influence of
      allelic variation at DBH on DbetaH biochemical phenotypic variation

PMID- 9654202
TI  - Three splicing defects, an insertion, and two missense mutations responsible for
      acute intermittent porphyria.
AB  - Three splicing defects (IVS1+3G-->T, 86A-->T, IVS13-2A-->G), an insertion
      (416insCA), and two missense mutations (664G-->A and 833T-->G) in the
      porphobilinogen deaminase (PBGD) gene were identified in six unrelated Finnish
      patients with acute intermittent porphyria (AIP). The IVS1+3G-->T substitution
      resulted in activation of a cryptic splice site in intron 1 and retention of a 67
      bp fragment in the mutant transcript. The 86A-->T mutation at the end of exon 3
      was predicted to cause an amino acid substitution (E29L). However, sequencing of
      the cDNA sample of the proband revealed exon 3 skipping from the mutant
      transcript. The IVS13-2A-->G substitution caused retention of intron 13 in the
      mutant transcript. In exon 8, 416insCA resulted in a frameshift. All three
      splicing defects and the CA insertion resulted in a truncated protein and thus,
      probably the loss of PBGD activity. The two novel missense mutations, 664G-->A in
      exon 12 and 833T-->C in exon 14 caused a single amino acid substitution (V222M
      and L278P). So far 25 different mutations have been characterized from 37 (93%)
      of a total of 40 unrelated Finnish AIP families, confirming the genetic
      heterogeneity of the disease even in a previously isolated area of Finland.

PMID- 9654203
TI  - High throughput fluorescence-based conformation-sensitive gel electrophoresis (F
      CSGE) identifies six unique BRCA2 mutations and an overall low incidence of BRCA2
      mutations in high-risk BRCA1-negative breast cancer families.
AB  - Mutational analysis of cancer susceptibility genes has opened up a new era in
      clinical genetics. In this report we present the results of mutational analysis
      of the BRCA2 coding sequences in 105 high-risk individuals affected with breast
      cancer and/or ovarian cancer and previously found to be negative for mutations of
      the BRCA1 coding sequence in our laboratory. These individuals have a positive
      family history with three or more cases of breast cancer and/or ovarian cancer at
      any age from the same side of the family tree. In order to perform a high
      throughput and reliable mutational analysis of the BRCA genes, we have adapted
      the conformation-sensitive gel electrophoresis mutation-scanning assay to a
      fluorescent platform. The advantages are speed, reproducibility and enhanced
      resolving power of the scanning method. Four unique mutations, including one
      missense and three frameshift mutations, were identified in the pool of 60 non
      Jewish patients (7%). Two cases of the 6174delT mutation were identified in the
      45 Ashkenazi Jewish individuals studied (5%). In addition, two novel frameshift
      mutations, not characteristic of the Jewish subgroup, were identified. Thus there
      were four mutations in total in this ethnic subgroup (9%). The six mutations
      identified in this combined patient pool, excluding the 6174delT mutations, are
      novel and have not been previously reported in the Breast Cancer Information Core
      (BIC) database. The results indicate that BRCA2 mutations account for the disease
      in less than 10% of this patient population. In addition, there is no significant
      difference in frequency of BRCA2 mutations between the Ashkenazi Jewish and non
      Jewish families in our clinical patient pool.

PMID- 9654204
TI  - Deletion mapping by FISH with BACs in patients with partial monosomy 22q13.
AB  - Patients with deletions in 22q13 are known to have phenotypic features that
      include normal or accelerated growth, large hands and feet, hypotonia, delayed
      psychomotor development and mild facial dysmorphism. To date, very few cases have
      been investigated by detailed molecular genetic analysis. We have analyzed three
      new patients with terminal deletions in 22q. We compared the cytogenetic
      observations with molecular data assessed by fluorescence in situ hybridization
      and an array of characterized bacterial artificial chromosome recombinants. The
      shortest region of deletion overlap is localized in 22q13.2-qter distal to the
      marker D22S94, but the telomeric repeat in the deleted chromosome appears to
      remain intact. When parental alleles were investigated in two of the three
      patients, the aberrant homolog was found to be of paternal origin in both cases.
      Although the deleted region still spans >20 cM, molecular analysis of additional
      patients and screening for new genes might help in elucidating candidate genes
      connected with the dysmorphisms defined by deletions of 22q13.

PMID- 9654205
TI  - LDL-R and Apo-B-100 gene mutations in Polish familial hypercholesterolemias.
AB  - A group of 30 Polish families with clinical signs of familial
      hypercholesterolemia was studied for the presence of germ-line mutations in the
      LDL-R and ApoB-100 genes. Screening of the LDL-R gene was performed at the
      genomic DNA level by single-strand conformation polymorphism analysis of all 18
      exons and extended by sequencing of polymerase chain reaction (PCR) products
      showing abnormalities. The occurrence of large LDL-R gene alterations was
      evaluated by analysis of restriction enzyme patterns on Southern blots and using
      the long-PCR technique. The ApoB-100 gene was studied by combined allele-specific
      and asymmetric PCR for the occurrence of the common B-3500 missense mutation G to
      A at nucleotide position 10,708. Germ-line mutations were found in 17 families.
      In 12 of them LDL-R gene mutations were detected. Three of 11 different mutations
      had previously been described in other populations (3-bp deletion of codon 197;
      Ser156Leu; Gly571Glu). Of the mutations not previously recognized and identified
      in Polish families, there were three small deletions (2-bp deletion AG at codon
      291; 4-bp deletion CCCT at codons 661-662; 1-bp deletion A at codon 830), and
      four point mutations (Arg239Stop, Cys331Stop, Asn543Ser, Gln665Stop).
      Additionally, one large (approximately 1-kb) LDL-R gene deletion between exons 6
      and 9 was identified. In five families, the B-3500 mutation within the ApoB-100
      gene was revealed.

PMID- 9654206
TI  - A quarter of men with idiopathic oligo-azoospermia display chromosomal
      abnormalities and microdeletions of different types in interval 6 of Yq11.
AB  - Cytogenetic investigations and molecular analysis of the Y chromosome by the
      polymerase chain reaction amplification of sequence-tagged sites (STS-PCR)
      technique were performed in 126 patients affected by idiopathic oligo-azoospermia
      following accurate selection of cases. Seventeen patients evidenced an abnormal
      karyotype. Fourteen patients with a normal karyotype had microdeletions of the Y
      chromosome within interval 6. In azoospermic patients microdeletions were
      scattered along different subintervals, while in oligozoospermic patients they
      were clustered in subinterval 6E. The size of the deletion was not apparently
      related to the severity of the disease. These results suggest that cytogenetic
      analysis and the STS-PCR technique can detect a genetic cause of infertility in
      about one-quarter of patients with idiopathic oligo-azoospermia.

PMID- 9654207
TI  - Partial biotinidase deficiency is usually due to the D444H mutation in the
      biotinidase gene.
AB  - Newborn screening for biotinidase deficiency has identified children with
      profound biotinidase deficiency (<10% of mean normal serum activity) and those
      with partial biotinidase deficiency (10%-30% of mean normal serum activity).
      Children with partial biotinidase deficiency and who are not treated with biotin
      do not usually exhibit symptoms unless they are stressed (i.e., prolonged
      infection). We found that 18 of 19 randomly selected individuals with partial
      deficiency have the transversion missense mutation G1330>C, which substitutes a
      histidine for aspartic acid444 (D444H) in one allele of the biotinidase gene. We
      have previously estimated that the D444H mutation results in 48% of normal enzyme
      activity for that allele and occurs with an estimated frequency of 0.039 in the
      general population. The D444H mutation in biotinidase deficiency is similar to
      the Duarte variant in galactosemia. The D444H mutation in one allele in
      combination with a mutation for profound deficiency in the other allele is the
      common cause of partial biotinidase deficiency.

PMID- 9654208
TI  - Structural organisation of the gene encoding the alpha-subunit of the human
      amiloride-sensitive epithelial sodium channel.
AB  - The human amiloride-sensitive epithelial sodium channel (ENaC) is a member of the
      degenerin/ENaC family of ion channels and regulates fluid and electrolyte
      absorption across a number of epithelia, including kidney, colon and lung. Native
      ENaC has been shown to be a multimer made up of at least three homologous
      subunits (alpha, beta, gamma) and mutations affecting the channel complex have
      been identified in various human diseases. "Gain of function" mutations in one of
      the three ENaC subunits have been found to cause pseudoaldosteronism (Liddle's
      syndrome) and ENaC "reduction of function" mutations are found in patients
      affected with the recessive form of pseudohypoaldosteronism (PHA) type 1. In this
      report, we describe the genomic organisation of the human alphaENaC gene. Human
      alphaENaC consists of 13 exons spanning 17 kb on chromosome 12p13 and contains at
      least eight Alu sequences. In addition to the intron/exon boundaries, we have
      deciphered almost all the intron sequences and 475 bp of the CCAAT-less and TATA
      less 5' flanking region.

PMID- 9654209
TI  - Cystic-fibrosis-like disease unrelated to the cystic fibrosis transmembrane
      conductance regulator.
AB  - Cystic fibrosis (CF) is considered to be a monogenic disease caused by molecular
      lesions within the cystic fibrosis transmembrane conductance regulator (CFTR)
      gene and is diagnosed by elevated sweat electrolytes. We have investigated the
      clinical manifestations of cystic fibrosis, CFTR genetics and electrophysiology
      in a sibpair in which the brother is being treated as having CF, whereas his
      sister is asymptomatic. The diagnosis of CF in the index patient is based on
      highly elevated sweat electrolytes in the presence of CF-related pulmonary
      symptoms. The investigation of chloride conductance in respiratory and intestinal
      tissue by nasal potential difference and intestinal current measurements,
      respectively, provides no evidence for CFTR dysfunction in the siblings who share
      the same CFTR alleles. No molecular lesion has been identified in the CFTR gene
      of the brother. Findings in the investigated sibpair point to the existence of a
      CF-like disease with a positive sweat test without CFTR being affected. Other
      factors influencing sodium or chloride transport are likely to be the cause of
      the symptoms in the patient described.

PMID- 9654210
TI  - Relative frequencies of cystic fibrosis mutations in The Netherlands as an
      illustration of significant regional variation in a small country.
AB  - Cystic fibrosis (CF) is one of the most common autosomal recessive disorders in
      white populations. Significant regional differences in CF mutations among
      affected individuals have been reported. We have studied the geographic
      distribution of the relative frequencies of the three most common Dutch CF
      mutations, deltaF508, A455E, and G542X, by analyzing data on area of residence of
      CF patients. Significantly higher relative frequencies of the A455E mutation and
      the G542X mutation were observed in the South-West and the South-East,
      respectively. A uniform distribution of relative frequencies was found for the
      deltaF508 mutation. The results of our study show that, even in a small country
      such as The Netherlands, certain CF mutations may be more common in one region
      than in another.

PMID- 9654211
TI  - Gross deletions of the neurofibromatosis type 1 (NF1) gene are predominantly of
      maternal origin and commonly associated with a learning disability, dysmorphic
      features and developmental delay.
AB  - Mutation screening in neurofibromatosis type 1 (NF1) families has long been
      hampered by the complexity of the NF1 gene. By using a novel multi-track
      screening strategy, 67 NF1 families (54 two-generation, 13 three-generation) with
      a de novo mutation in the germline of the first generation were studied with two
      extragenic and 11 intragenic markers. The pathological lesion was identified in
      31 cases. Loss of heterozygosity (LOH) in the affected individual revealed a
      gross gene deletion in 15 of the two-generation families; in 12 (80%) of them,
      the deletion was maternally derived. Eleven patients with a gross deletion
      exhibited developmental delay, ten had dysmorphic features and six manifested a
      learning disability. No gross deletion was apparent in any of the 13 three
      generation families, suggesting that such lesions are subject to more intense
      selection. In these families, the new mutation was of paternal origin in 11
      kindreds and the underlying mutational event could be characterised in three of
      them.

PMID- 9654212
TI  - The effects of splice site mutations in patients with naevoid basal cell
      carcinoma syndrome.
AB  - We have previously identified the human homologue of the Drosophila patched gene
      and have described, in this gene, mutations that give rise to naevoid basal cell
      carcinoma syndrome (NBCCS). Here, we have analysed the effects of three splice
      site mutations within human PATCHED (PTCH) by the reverse
      transcription/polymerase chain reaction method in cultured patient lymphocyte
      cell lines. Two alterations, a point mutation in intron 7 and an insertion in
      intron 10, lead to premature truncation of the PATCHED protein. Another point
      mutation in intron 17 results in the skipping of exon 18 and the subsequent in
      frame deletion of 46 amino acids. Additionally, in all lymphocyte and
      keratinocyte cell lines examined, exon 10 of PTCH is alternatively spliced
      leading to an in-frame deletion of 52 amino acids.

PMID- 9654214
TI  - Respiratory depression produced by intravenously administered NBQX.
AB  - To determine whether blockade of non-N-methyl-D-aspartate (non-NMDA) excitatory
      amino acid receptors affects breathing, we administered the non-NMDA receptor
      antagonist, 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX), to
      anesthetized cats while monitoring phrenic nerve discharge, blood pressure and
      heart rate. NBQX, 3 and 10 mg/kg, i.v., reduced phrenic amplitude 59 +/- 20% (n =
      3) and 88 +/- 6% (n = 5), respectively, and decreased respiratory rate. Phrenic
      activity was completely silenced in 3 animals. These effects were accompanied by
      decreased blood pressure and heart rate. Our data indicate that NBQX, a
      competitive antagonist of non-NMDA receptors, is a powerful depressant of
      cardiorespiratory activity.

PMID- 9654213
TI  - The contractile effect of fedotozine on guinea pig isolated intestinal cells is
      not mediated by kappa opioid receptors.
AB  - The compound fedotozine, recently described as a peripheral kappa opioid receptor
      agonist, was tested on smooth muscle cells isolated from the longitudinal muscle
      layer of the guinea pig ileum, in comparison with the selective kappa receptor
      agonist, compound U-50488. Fedotozine (1 nmol/l-1 micromol/l) caused a
      concentration-dependent contraction of intestinal cells, with a maximum decrease
      in cell length not significantly different from that caused by acetylcholine. The
      kappa agonist U-50488 (0.1 pmol/l-100 nmol/l) was without effect. The contractile
      effect of fedotozine was not significantly modified by naloxone (0.1-1
      micromol/l). These results indicate that fedotozine can have direct excitatory
      effects on intestinal smooth muscle cells from the guinea pig ileum not mediated
      by activation of kappa opioid receptors.

PMID- 9654215
TI  - Acute natriuretic effect of fasidotrilat, a mixed inhibitor of neutral
      endopeptidase and angiotensin I-converting enzyme, in rats with heart failure.
AB  - The acute diuretic and natriuretic effects of fasidotrilat, a mixed inhibitor of
      neutral endopeptidase (NEP) and angiotensin I-converting enzyme (ACE) were
      evaluated in control and myocardial-infarcted rats. Fasidotrilat injection (10
      mg/kg i.v.) had no significant effect on arterial blood pressure and led to
      significant elevations in urine volume (+57% in control rats and +114% in
      infarcted rats) and of urinary sodium excretion (+81% in control rats and +225%
      in infarcted rats). Comparison between control and infarcted rats showed that
      fasidotrilat-induced changes in diuresis and natriuresis were higher in infarcted
      rats (2.4-fold for diuresis and 4.7-fold for natriuresis, p < 0.05), despite a
      lower perfusion pressure (-10 mm Hg) in infarcted rats. These data show the
      potential therapeutic interest of mixed NEP/ACE inhibitors in congestive heart
      failure.

PMID- 9654216
TI  - Pharmacokinetics and pharmacodynamics of mibefradil in hypertensive patients with
      varying degrees of renal insufficiency.
AB  - Mibefradil, the first member of the tetralol derivatives, a new class of calcium
      antagonists, is used for the treatment of hypertension and angina pectoris. This
      study was designed to investigate the effect of varying degrees of chronic renal
      impairment on mibefradil pharmacokinetics and pharmacodynamics. Neither
      pharmacokinetic nor pharmacodynamic parameters varied as a function of renal
      status. Additionally, hemodialysis removed only a relatively small fraction of
      drug from the body. It was concluded that the majority of renal-failure patients
      will not require a change in mibefradil dosage relative to patients with normal
      renal function. Following hemodialysis, supplemental mibefradil treatment should
      not be necessary.

PMID- 9654217
TI  - Effects of ketoconazole on digoxin absorption and disposition in rat.
AB  - Digoxin, a cardiac glycoside, is a substrate of the multidrug transporter P
      glycoprotein (Pgp), and in rats has also been identified as a substrate for
      cytochrome P450 3A (CYP3A). Ketoconazole, an antifungal agent, was shown to
      inhibit Pgp in a multidrug-resistant cell line, and is known to be a potent
      inhibitor of CYP3A. Here, we determined the effects of ketoconazole on digoxin
      absorption and disposition in rats. Digoxin was administered intravenously or
      orally with or without a concomitant oral dose of ketoconazole. When given
      intravenously, digoxin AUC increased from 93 +/- 22 to 486 +/- 26 microg x h/l
      with ketoconazole administration. Similarly, ketoconazole raised the AUC of
      orally administered digoxin from 63 +/- 17 to 411 +/- 50 microg x h/l.
      Concomitant ketoconazole administration prolonged digoxin elimination, yielding a
      nonlinear pharmacokinetic profile. Using time-averaged values, digoxin
      bioavailability increased from 0.68 +/- 0.18 to 0.84 +/- 0.10, while mean
      absorption time was reduced from 1.1 +/- 0.4 to 0.3 +/- 0.1 h. Thus, in rats,
      ketoconazole increases digoxin plasma concentrations, rate of absorption and
      bioavailability. Although the effects of ketoconazole on AUC could be explained
      by inhibition of both CYP3A and Pgp, which cannot be differentiated in this
      study, the decreased mean absorption time can only be explained by inhibition of
      Pgp in the intestine.

PMID- 9654218
TI  - A method for measuring naringenin in biological fluids and its disposition from
      grapefruit juice by man.
AB  - The major flavonoid in grapefruit juice, naringin, has an aglycone, naringenin,
      that inhibits some oxidations in vitro and may have in vivo activity. We
      developed an HPLC method to measure naringenin using a methanol:water mobile
      phase with UV absorbance detection. The recovery of naringenin was 96%. Two
      subjects who drank grapefruit juice containing 214 mg naringin daily excreted
      approximately 30 mg/day of naringenin glucuronide. Thus, naringin is hydrolyzed
      to naringenin and then conjugated with glucuronic acid prior to excretion of the
      conjugate.

PMID- 9654219
TI  - Predictive sensitivity of human cancer cells in vivo using semipermeable
      polysulfone fibers.
AB  - An in vivo experimental model was developed to predict efficiently and accurately
      chemosensitivity of human tumors. Human cancer cells either from cultured cell
      lines or from patients' tumors were injected directly into semipermeable
      polysulfone fibers subsequently implanted into immunocompetent rats. Results
      suggest utility of this novel model system for predicting tumor sensitivity to a
      wide range of anticancer agents and for potentially guiding the treatment of
      cancer patients in the clinical setting.

PMID- 9654220
TI  - Preserved autonomic modulation of the sinus and atrioventricular nodes following
      posteroseptal ablation for treatment of atrioventricular nodal reentrant
      tachycardia.
AB  - INTRODUCTION: Following radiofrequency catheter ablation of AV nodal reentrant
      tachycardia (AVNRT), inappropriate sinus tachycardia may occur, possibly due to
      damage to autonomic cardiac nerve fibers. Furthermore, inducibility of AVNRT is
      often critically dependent on the autonomic balance. We investigated whether
      successful ablation of AVNRT is associated with an alteration of autonomic input
      to the sinus and AV nodes. METHODS AND RESULTS: To estimate changes in the
      autonomic modulation of the sinus and AV nodes, power spectra of beat-to-beat PP
      and PR intervals were analyzed from high-quality nighttime ECG recordings of 11
      patients before and after radiofrequency application. Normalized HF power (nHF)
      of PP and PR intervals was used as an index of efferent vagal modulation and the
      LF/HF ratio as an index of sympathovagal balance of the sinus node (PP) and AV
      node (PR). Before ablation, LF/HF(PP) was 3.2 and nHF(PP) was 0.3 in the sinus
      node. For the AV node, LF/HF(PR) was 1.2 and nHF(PR) was 0.5. Following ablation,
      LF/HF(PP) (3.5) and nHF(PP) (0.3) of the PP intervals did not change. Similarly
      to the sinus node, there were no changes in the autonomic modulation of the AV
      node, as both LF/HF(PR) (1.2) and nHF(PR) (0.5) remained unchanged. CONCLUSION:
      Our results indicate that autonomic control of the sinus and AV nodes is
      preserved following successful radiofrequency ablation of AVNRT. The effects of
      posteroseptal radiofrequency current application are not necessarily mediated by
      changes in the autonomic input to the AV node.

PMID- 9654221
TI  - Lack of benefit of very short basic drive train cycle length or repetition of
      extrastimulus coupling intervals for induction of ventricular tachycardia.
AB  - INTRODUCTION: There are considerable variations of uncertain importance in basic
      drive train cycle lengths and degree of repetition of extrastimuli used in
      programmed ventricular stimulation protocols in different laboratories. We
      compare prospectively three different stimulation protocols to examine the
      influence of a short basic drive train cycle length and repetition of
      extrastimuli on induction of ventricular tachycardia. METHODS AND RESULTS: Thirty
      consecutive patients who had documented ventricular tachycardia or fibrillation
      based on underlying coronary artery disease underwent programmed ventricular
      stimulation with each of the three study protocols. Protocol A used a basic drive
      train cycle length of 400 msec with each extrastimulus coupling interval
      delivered only once. Protocol B used the same basic drive train cycle length, but
      with each extrastimulus coupling interval repeated three times before
      decrementing. Protocol C used 300 msec as the cycle length of basic drive trains
      without repetition of extrastimuli. Sixty-three percent, 67%, and 63% of the
      study patients had ventricular tachycardia inducible with protocols A, B, and C,
      respectively (P = NS). Ventricular fibrillation was induced in 23% of the 30
      patients in all three protocols. There were no significant differences in the
      mean cycle lengths of induced ventricular tachycardia, the number of extrastimuli
      used, and the coupling interval of the last extrastimulus inducing ventricular
      tachycardia among the three protocols. CONCLUSION: This study showed no clinical
      benefit for repetition of extrastimuli that have failed to induce a ventricular
      tachyarrhythmia during programmed ventricular stimulation. A short basic cycle
      length of 300 msec was not superior to 400 msec for induction of ventricular
      tachyarrhythmias. We recommend the use of basic cycle length 400 msec with
      delivery of each extrastimulus interval only once as the initial protocol for
      programmed ventricular stimulation.

PMID- 9654222
TI  - Effect of electrode length on atrial defibrillation thresholds.
AB  - INTRODUCTION: Catheter-based electrodes have been used previously to terminate
      episodes of atrial fibrillation in animals and man. Typically, these electrodes
      span 6 to 7 cm, and lowest energy requirements are achieved when these electrodes
      are positioned in the distal coronary sinus and in the right atrium. The purpose
      of this study was to evaluate the use of longer electrode lengths for atrial
      defibrillation. METHODS AND RESULTS: In 15 patients, two decapolar catheters were
      inserted, one into the distal coronary sinus and one in the right atrium. To
      provide longer electrodes lengths, a third catheter was inserted and alternated
      positioned in the right atrium or coronary sinus. A 6-cm electrode span was
      obtained by using the distal 8 rings on the coronary sinus catheter or 8
      consecutive electrodes on the right atrial catheter and increased from 6 to 11 cm
      by connecting 5 consecutive, nonoverlapping rings of the third catheter with the
      10 rings of the initial right atrial or coronary sinus catheter. Atrial
      defibrillation thresholds were determined twice, in a randomized order, in each
      patient for each of the three combinations of electrode lengths. All 15 patients
      could be successfully converted to sinus rhythm without complications; however,
      one patient could be converted reproducibly with only 2 of the 3 electrode
      combinations. Mean thresholds were 306 +/- 102 V, 5.9 +/- 4.0 J for the 6 cm/6 cm
      electrode length combination with an impedance of 72 +/- 18 omega. For the
      electrode combination using the 11-cm electrode in the right atrium, the
      defibrillation threshold was 296 +/- 107 V, 5.8 +/- 3.9 J with an impedance of 61
      +/- 17 omega and was 294 +/- 91 V, 5.6 +/- 3.6 J with an impedance of 55 +/- 11
      omega for the 11-cm electrode in the coronary sinus. There were no significant
      differences in defibrillation voltage or energy (P > 0.05) associated with the
      longer electrode lengths; however, the longer electrode lengths did significantly
      lower shock impedance (P < 0.05). CONCLUSION: The use of longer electrodes, when
      using the right atrium to coronary sinus shock vector, does not lower the
      defibrillation requirements for restoration of sinus rhythm.

PMID- 9654223
TI  - Immediate reproducibility of upper limit of vulnerability measurements in
      patients undergoing transvenous implantable cardioverter defibrillator
      implantation.
AB  - INTRODUCTION: Measurement of the upper limit of vulnerability (ULV) with
      monophasic T wave shocks has been proposed as a patient-specific measurement of
      defibrillation efficacy that results in fewer episodes of ventricular
      fibrillation (VF) than measurement of a defibrillation efficacy curve. METHODS
      AND RESULTS: We sought to determine the magnitude of variance in ULV in 63
      consecutive patients undergoing implantation of an implantable cardioverter
      defibrillator (ICD). We measured ULV as the strength at or above which VF is not
      induced when a stimulus is delivered at 310 msec after an 8-beat ventricular
      pacing drive at 400 msec. Defibrillation threshold (DFT) was measured in patients
      with an active can device using a biphasic waveform and the binary search method
      beginning at 12 J. Sixty-three patients were studied; they had a mean age of 62
      +/- 12 years and a mean ejection fraction of 35% +/- 15%. Three quarters of
      patients had an ischemic cardiomyopathy. Each patient underwent 4.5 +/- 0.8
      measurements of ULV. Monophasic ULV correlated poorly with biphasic DFT (R
      between 0.19 and 0.28, P = 0.04 to 0.17). There was no change in ULV between
      second to third, third to fourth, and first to last measurement in 22% to 41% of
      patients. The reliability coefficient was 0.87. A ULV > or = 20 J was found in
      eight patients. The only predictor of high ULV was a high DFT. CONCLUSION:
      Monophasic ULVs do not closely predict biphasic active can DFTs using a standard
      protocol. High DFTs were predicted by high ULVs. There was little variation in
      the acute measurement of ULV between trials. These findings have important
      implications for using ULV measurements to determine changes in DFTs after
      interventions. The methodology of determining ULV is critical to its use for
      predicting DFTs and programming ICDs.

PMID- 9654224
TI  - Altered pattern of connexin40 distribution in persistent atrial fibrillation in
      the goat.
AB  - INTRODUCTION: Since altered expression of gap junction proteins (connexins) in
      diseased myocardial tissue may lead to abnormal electrical coupling between
      cardiomyocytes and hence contribute to arrhythmogenesis, the expression of
      connexin(Cx)40 and Cx43 was studied in atrial appendage from goats in sinus
      rhythm (SR) and persistent atrial fibrillation (AF). METHODS AND RESULTS:
      Biopsies were taken from the left and right atrial appendages from goats in SR or
      after pacing-induced persistent AF. Analyses of Cx40 and Cx43 mRNA and protein
      levels, using quantitative (competitive) polymerase chain reaction and western
      blotting, respectively, revealed no significant changes in the overall expression
      of Cx40 and Cx43 as a result of persistent AF. At the cellular level,
      immunohistochemistry and confocal laser scanning microscopy showed a homogeneous
      distribution of either connexin in atrial sections taken during SR. After
      induction of AF, the distribution of Cx43 gap junctions was unchanged whereas the
      Cx40 pattern showed marked inhomogeneities with small areas (0.15 to 0.6 mm in
      diameter, 25% of section surface area) of low-density Cx40 located between larger
      areas of normal (unchanged) Cx40 density. Activation mapping (244 electrodes,
      spatial resolution 2.25 mm) of the right atrial wall did not reveal changes in
      atrial conduction velocity. CONCLUSION: Pacing-induced persistent AF in the goat
      gave rise to changes in the spatial organization of Cx40 gap junctions. Although
      the overall conduction velocity appeared not to have changed,
      microheterogeneities in conduction due to the local redistribution of Cx40 gap
      junctions might have contributed to the initiation and maintenance of AF.

PMID- 9654225
TI  - Connexins, conduction, and atrial fibrillation.

PMID- 9654226
TI  - Antibodies against myosin in sera of patients with idiopathic paroxysmal atrial
      fibrillation.
AB  - INTRODUCTION: Circulating autoantibodies against myosin heavy chain have been
      detected in patients with ventricular myocarditis and in patients with dilated
      cardiomyopathy. This study investigated the presence of antibodies against myosin
      in sera of healthy control persons as compared with patients with idiopathic
      paroxysmal atrial fibrillation refractory to antiarrhythmic therapy. METHODS AND
      RESULTS: An SDS-PAGE (sodium dodecylsulfate polyacrylamide gel electrophoresis)
      procedure, followed by Western blotting with homogenates and membrane fractions
      of human left ventricular and atrial specimen as antigens, was used to analyze
      sera of 10 patients with idiopathic paroxysmal atrial fibrillation and 10 age
      matched healthy control subjects. Circulating immunoglobulin G reactivity against
      cardiac myosin heavy chain was detected in 6 patients (60%) as compared with 1
      control subject (10%). This difference was statistically significant (P < 0.05).
      All patients with idiopathic paroxysmal atrial fibrillation who showed reactivity
      against myosin heavy chain also had specific reactivity in their sera that
      exhibited reactivities to both ventricular and atrial cardiac myosin heavy chain
      isoforms. CONCLUSION: This study demonstrates the presence of circulating
      autoantibodies against myosin heavy chain in a significant percentage of patients
      with idiopathic paroxysmal atrial fibrillation and raises the possibility of an
      autoimmune process in some patients with paroxysmal atrial fibrillation.

PMID- 9654227
TI  - Lone atrial fibrillation and autoantibodies: cause versus effect.

PMID- 9654228
TI  - Novel donor splice site mutation in the KVLQT1 gene is associated with long QT
      syndrome.
AB  - INTRODUCTION: Inherited long QT syndrome (LQTS) recently has been associated with
      mutations in genes coding for potassium (KVLQT1, KCNE1, and HERG) or sodium
      (SCN5A) ion channels involved in regulating either sodium inward or potassium
      outward currents of heart cells, resulting in prolongation of the repolarization
      period. We describe a new mutation, a -1 donor splice site mutation in a kindred
      with two affected members (QTc = 0.61 and 0.54 sec). METHODS AND RESULTS: Single
      stranded conformation polymorphism (SSCP) analyses were performed on DNA
      fragments amplified by polymerase chain reaction from DNA extracted from whole
      blood. Aberrant conformers were analyzed by DNA sequencing. SSCP analysis of the
      KVLQT1 gene revealed an aberrant conformer in the affected family members. DNA
      sequencing confirmed the presence of a G-->A change in the last nucleotide of
      codon 344. This mutation does not cause an amino acid change, but a change of the
      splice site characteristics at the 3' end of exon 6. The mutation may affect,
      through deficient splicing, the putative sixth transmembrane segment of the K+
      channel, and this type of mutation has not previously been described in KVLQT1.
      CONCLUSION: The clinical course of LQTS in the affected family members, in whom
      no deaths occurred despite 20 to 30 syncopes, can be explained by the ability of
      the cellular machinery to perform partial correct splicing in the mutant allele.
      This type of mutation may be misinterpreted as a normal variant, since it is a
      point mutation causing neither an amino acid change nor the introduction of a
      stop codon.

PMID- 9654229
TI  - Nonfluoroscopic transseptal catheterization: safety and efficacy of intracardiac
      echocardiographic guidance.
AB  - INTRODUCTION: Recently, there has been a revival in the use of transseptal
      catheterization due to the development of balloon mitral valvuloplasty and
      radiofrequency catheter ablation. Complications of transseptal puncture, although
      rare, can be serious and life-threatening. In the present study, we evaluated the
      use of intracardiac echocardiography (ICE) as the sole imaging modality to guide
      transseptal puncture and catheterization. METHODS AND RESULTS: In each animal, 10
      transseptal punctures were performed guided solely by ICE. The standard approach
      to transseptal catheterization using a Brockenbrough needle and long vascular
      sheath was used except for the use of ICE instead of fluoroscopy. A 6.2
      French/12.5-MHz and 9-French/9-MHz ICE catheter was used for imaging. At the end
      of each study, pathologic evaluation was performed. Transseptal puncture was
      performed safely, guided solely by ICE, in each of 100 attempts (five attempts
      guided by each ICE catheter in 10 dogs). While the fossa ovalis was easily
      visualized with both ICE catheters, the 9-French/9-MHz catheter offered an
      enhanced field of view. On pathologic evaluation, there was no evidence of
      perforation of either the right or left atrium outside of the fossa ovalis.
      CONCLUSION: Both ICE catheters used in this trial allowed for excellent
      visualization of the fossa ovalis and safe transseptal puncture. Intracardiac
      echocardiography may be a better imaging modality than fluoroscopy for guiding
      transseptal catheterization, especially in less experienced hands.

PMID- 9654230
TI  - Origin of heat-induced accelerated junctional rhythm.
AB  - INTRODUCTION: The application of high-frequency current to the AV junctional area
      results in a temperature rise in the myocardium and may cause accelerated
      junctional rhythm (AJR). The aim of the study was to characterize heat-induced
      AJR in an in vitro animal model. METHODS AND RESULTS: Studies were performed in
      isolated perfused pig and rabbit hearts. Using a small heating probe, we could
      induce AJR from a discrete area located in the middle of the triangle of Koch,
      which was smaller than the area from which RF energy application could elicit
      AJR. Histology showed that the heat-sensitive area was located over, or close to,
      the compact AV node. It did not correspond with the areas where double potentials
      were found or with the site(s) of earliest atrial activation during VA
      conduction. Microelectrode recordings revealed that AJR arose in nodal-type
      cells. Heat increased the slope of the phase 4 depolarization and shortened the
      action potential duration. Two types of AJR were observed: the first one was
      regular and the second one showed irregularity in the intervals. Interaction of
      multiple foci and the presence of conduction block between the foci and the His
      bundle caused the irregularity of the His-His intervals during the second type of
      AJR. CONCLUSION: AJR observed during heat and RF application in the AV nodal area
      results from the effect of heat on AV nodal cells with underlying pacemaker
      activity. The heat-sensitive area is located over, or very close to, the compact
      AV node.

PMID- 9654231
TI  - Familial sudden cardiac death associated with a terminal QRS abnormality on
      surface 12-lead electrocardiogram in the index case.
AB  - A case is presented of an 18-year-old male who had been resuscitated following an
      episode of sudden death due to ventricular fibrillation. The patient was noted to
      have an abnormal deflection in the terminal QRS on surface ECG and an abnormal
      signal-averaged ECG demonstrating a late potential coincident with the terminal
      QRS abnormality on the ECG. The patient had easily inducible polymorphic
      ventricular tachycardia during electrophysiologic study, which was suppressed by
      quinidine but not by procainamide or beta blockers. The surface ECG and signal
      averaged ECG also were normalized by quinidine but not by procainamide or beta
      blockers. The patient had no further arrhythmias on quinidine for 6 years until
      he inexplicably discontinued his medication and died suddenly shortly thereafter.
      The present case may represent a unique familial sudden death syndrome or
      possibly a variant of the sudden death syndrome associated with right bundle
      branch block and ST elevation in V1 through V3. Currently available data suggest
      that, in such patients, an implantable cardioverter defibrillator may provide
      better protection from sudden death than does antiarrhythmic drug therapy.

PMID- 9654232
TI  - Emergence of bidirectional accessory pathway conduction in adulthood.
AB  - A 30-year-old woman presented with tachycardiomyopathy due to atrial flutter
      fibrillation and underwent radiofrequency ablation of the AV node and VVIR
      pacemaker implantation. There was no evidence of any accessory pathway (AP)
      conduction during the AV nodal ablation or during chronic ventricular pacing. One
      year later, she had a transient preexcited tachycardia. A year after this, her
      ECG showed 1:1 AV conduction with preexcitation. Electrophysiologic study
      revealed a left lateral AP with anterograde and retrograde refractory periods of
      280 and 240 msec, respectively. Successful radiofrequency ablation of the AP was
      performed. This case highlights a unique emergence of an AP in adult life.

PMID- 9654233
TI  - Becker muscular dystrophy with bundle branch reentry ventricular tachycardia.
AB  - This report describes a case of Becker muscular dystrophy presenting with
      recurrent symptomatic wide complex tachycardia. Electrophysiologic testing
      demonstrated the mechanism to be bundle branch reentry ventricular tachycardia.
      It is important to consider this potential mechanism in patients with ventricular
      arrhythmias who have this particular clinical entity, since radiofrequency
      catheter ablation can represent a curative treatment.

PMID- 9654234
TI  - Effects of gender on cardiac arrhythmias.
AB  - The purpose of this study is to review published data regarding gender
      differences in cardiac electrophysiology and in the occurrence of clinical
      arrhythmias. ECG differences between men and women include a faster resting heart
      rate in women, a longer corrected QT interval, and a lower QT dispersion than in
      men. The faster resting heart rate in women appears to be primarily related to
      differences in physical conditioning. The mechanism for the longer corrected QT
      interval in women is not completely known, but does not appear to be related to
      acute effects of estrogen or progesterone or differences in autonomic
      innervation. Women also appear to have a lower incidence of atrial fibrillation,
      a difference in the age distribution of supraventricular tachycardia, and a lower
      incidence of sudden death than men. Much of the lower incidence of sudden death
      in women may relate to a difference in the prevalence of coronary artery disease,
      but other factors such as inherent differences in repolarization, which may be
      reflected by a gender difference in the corrected QT interval, also may be
      operative. The paradox of a longer corrected QT interval and higher incidence of
      torsades de pointes, but lower population-based incidence of sudden death in
      women, has not been completely resolved. Further studies will be required to help
      better understand the basic mechanisms involved in gender differences in
      electrophysiology and arrhythmias and determine the extent to which these
      differences have implications for clinical management of cardiac arrhythmias.

PMID- 9654235
TI  - Sex steroids and cardiac arrhythmia: more questions than answers.

PMID- 9654236
TI  - Management of patients with the hereditary long QT syndrome.
AB  - The hereditary long QT syndrome is an inherited ion channel disorder with QT
      prolongation, morphologic changes in the T waves, and a relatively high frequency
      of syncope, T wave alternans, torsades de pointes-type ventricular tachycardia,
      and sudden death. Monotherapy with beta blockers is the treatment of first
      choice. In patients with recurrent syncope despite therapy with beta blockers,
      pacemakers and/or ganglionectomy may be useful in selected cases, with an
      implantable cardioverter defibrillator used as a fail-safe approach in high-risk
      patients.

PMID- 9654237
TI  - Narrow QRS complex tachycardia with apparent 2:1 QRS to P wave ratio.

PMID- 9654238
TI  - Follow-up biological and genotoxicological monitoring of acrylonitrile- and
      dimethylformamide-exposed viscose rayon plant workers.
AB  - In order to investigate the genotoxic effects of occupational acrylonitrile (ACN)
      and dimethylformamide (DMF) exposures, clinical serum and urine parameters and
      genotoxicological endpoints such as chromosome aberration (CA), sister chromatid
      exchange (SCE), high frequency SCE (HFC), cell cycle kinetics, and UV-induced
      unscheduled DNA synthesis (UDS) were followed up three times during a 20-month
      period in peripheral blood lymphocytes (PBL) of 26 workers (13 maintainers and 13
      fiber producers) occupationally exposed to ANC and/or DMF in a viscose rayon
      plant, 26 matched control subjects, and six industrial controls (all males). Six
      of the 26 exposed subjects were hospitalized because of liver dysfunction that
      had developed due to inhalative DMF exposure. The rate of smoking was estimated
      on the basis of serum thiocyanate (SCN) levels. Average peak air ACN and DMF
      concentrations were over the maximum concentration limits at the time of both
      investigations. Urine ACN and monomethyl-formamide (MMF) excretions of the
      exposed subjects were almost doubled after work shifts. An increase in lymphocyte
      count (in months 0 and 7), and severe alterations in the liver function were
      observed in the exposed subjects. In PBLs the proliferative rate index (PRI) was
      already increased in month 0 compared with the controls. In each study,
      significant increases in CA and SCE frequencies, as well as increases in UDS were
      found in PBLs of the exposed subjects. The frequencies of chromatid breaks and
      acentric fragments further increased in month 7 and remained constantly elevated
      in month 20. Increased yields of both chromatid and chromosome-type exchange
      aberrations first appeared in month 20, when HFCs were 2.72 times more frequent
      in fiber producers than in maintainers. The role of some important biological
      confounding factors (age, white blood cell count, and hematocrit) and lifestyle
      confounding factors (smoking and drinking habits) were subjected to an analysis
      of variance during the second study. Increased CA, SCE, and UDS were found both
      in control and exposed smokers when current smoking was established on the basis
      of the serum SCN levels. The cytogenetic data suggest that occupational exposures
      to ACN and DMF induce considerable genotoxic consequences and may increase the
      cancer risk in the exposed human populations.

PMID- 9654239
TI  - Influence of GSTT1 genotype on sister chromatid exchange induction by styrene-7,8
      oxide in cultured human lymphocytes.
AB  - The genetic polymorphisms of glutathione S-transferases (GSTs), which are
      involved in the metabolic inactivation of various toxicants, have been suggested
      to be an important source of variation in individual response to genotoxic
      carcinogens. We have previously shown that donor GSTM1 genotype does not
      influence the induction of sister chromatid exchanges (SCEs) in cultured human
      lymphocytes by styrene-7,8-oxide (SO), a metabolite of styrene. Here, we expanded
      the study to GSTT1 polymorphism. SCEs were analyzed from 72-hr whole-blood
      lymphocyte cultures of five GSTT1 positive (at least one undeleted allele) and
      five GSTT1 null (gene homozygously deleted) donors, all GSTM1 positive, after a
      48-hr treatment with 50 microM and 150 microM SO. SO clearly increased SCEs in
      cultures of all donors. The mean number of SCEs/cell induced by SO (individual
      mean SCEs from acetone-treated control cultures subtracted) was 1.7 (50 microM)
      and 1.4 (150 microM) times greater among the GSTT1 null individuals (4.83 at 50
      microM, 18.98 at 150 microM) compared with the GSTT1 positive individuals (2.78
      at 50 microM, 13.74 at 150 microM), the differences being statistically
      significant (P=0.006 and P=0.022, respectively). These findings show that the
      lack of the GSTT1 gene increases the genotoxic effects of SO in human whole-blood
      lymphocyte cultures, suggesting that GSTT1 is involved in the detoxification of
      SO in humans. Although glutathione conjugation is considered a minor metabolic
      pathway for SO in vivo, the high GSTT1 activity in erythrocytes may be important
      locally and might affect the level of genotoxic damage observed in peripheral
      lymphocytes of styrene-exposed reinforced plastics workers. The GSTT1
      polymorphism could also influence the urinary excretion of SO-specific
      mercapturic acids.

PMID- 9654240
TI  - Chromosome aberrations in vitro related to cytotoxicity of nonmutagenic chemicals
      and metabolic poisons.
AB  - Chromosome aberrations can occur by secondary mechanism(s) associated with
      cytotoxicity, induced by chemicals that do not attack DNA. Aberrations are formed
      from DNA double-strand breaks, and DSBs are known to be induced by nonmutagenic
      (Ames test negative) noncarcinogens at toxic levels [Storer et al. (1996): Mutat
      Res 368:59-101]. Here, 8 of 12 of these chemicals caused aberrations in CHO cells
      at cytotoxic doses, and often only when cell counts (survival) at 20 hr
      approached < or =50% of controls. Five of eight noncarcinogens (2,4,
      dichlorophenol, dithiocarb, menthol, phthalic anhydride, and ethionamide) and one
      of two equivocal carcinogens (bisphenol A) caused aberrations, usually over a
      narrow dose range with steeply increasing cytotoxicity. Phthalic anhydride and
      ethionamide were positive only at doses with precipitate. Phenformin was negative
      even at toxic doses and ephedrine and phenylephrine were negative and gave little
      toxicity. Aberrations were also induced by metabolic poisons, 2,4-dinitrophenol,
      (uncouples oxidative phosphorylation), and sodium iodoacetate, (Nal; blocks ATP
      production). Five of the chemicals that induced aberrations in CHO cells were
      tested in human TK6 cells and four were positive, the fifth being equivocal.
      Stable aberrations (translocations) were induced in human cells by Nal. Clearly,
      chemicals can give "false-positive" results in the chromosome aberration assay at
      cytotoxic levels, though cytotoxicity does not always produce aberrations, so
      that further information (e.g., DNA reactivity) is needed to determine whether a
      result is a "false-positive." Primary DNA-damaging chemicals such as alkylators
      are also cytotoxic, but give strong increases in aberrations without marked
      initial toxicity by the measures used here, although the aberrations they induce
      do reduce long-term survival in colony-forming assays.

PMID- 9654241
TI  - Specificity of base substitution mutations induced by the dietary carcinogens 2
      amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhlP) and 2-amino-3
      methylimidazo[4,5-f]quinoline (IQ) in Salmonella.
AB  - The base pair substitution mutational profiles induced by the heterocyclic amine
      cooked food mutagens PhlP and IQ in Salmonella typhimurium strains TA100 and
      TA1535 were determined by colony hybridization analysis. Both PhlP and IQ induced
      predominantly GC-->TA transversions in strain TA100 (rfa,delta uvrB/pKM101) with
      a pronounced preference for the second codon position (CCC--> CAC; 72% of total).
      PhlP also reverted strain TA1535 (rfa, delta uvrB) efficiently at concentrations
      similar to those required for strain TA100. In contrast to the PhlP-induced
      mutational profile observed in strain TA100, in strain TA1535 PhlP induced
      exclusively GC-->AT transitions at the second codon position (CCC-->CTC; 96-99%
      of total). Base substitution mutagenesis induced by heterocyclic amines related
      to PhlP is generally SOS-dependent, requiring the presence of plasmid pKM101 in
      Salmonella hisG46 strains. Thus, the SOS dependent reversion of S. typhimurium
      strain TA100 probably reflects error-prone lesion bypass at the major PhlP-
      guanosine adduct at the C-8 position. The GC-->AT transition mutations induced by
      PhlP in strain TA1535 appear to be SOS-independent, however, suggesting that
      these mutations may arise from the formation of PhlP-DNA adducts other than the
      replication-blocking C8-dG lesion.

PMID- 9654242
TI  - Monofunctional adenine N-3 adducts of melphalan: occurrence at a mutational
      hotspot sequence and resistance to removal by AlkA protein.
AB  - Previous work showed that a CTAAA sequence in the supF gene of the shuttle
      plasmid pZ189 was a hotspot for mutagenesis by the aromatic nitrogen mustards
      melphalan and chlorambucil, and indirect evidence suggested adenine N-3 adducts
      as premutagenic lesions. In order to characterize the adducts formed at this
      sequence more directly, a substrate was prepared in which the three adjacent
      adenines in the CTAAA sequence were 3H-labeled. Following treatment of this
      substrate with [14C]melphalan, thermolabile adducts were depurinated and analyzed
      by HPLC. Only a single peak bearing both 3H and 14C label was detected and it
      coeluted with the single major adduct formed by the reaction of melphalan with
      free adenine base. Various spectrometric analyses of this species were all
      consistent with its identification as a monofunctional adenine N-3 adduct of
      melphalan. There was no evidence for any bifunctional adducts involving the
      labeled adenines. There was little if any release of the adenine N-3 adduct of
      melphalan by Escherichia coli AlkA protein, under conditions where 3
      methyladenine was quantitatively released. The results support the proposal that
      monofunctional adenine N-3 adducts are intermediates in the generation of A.T-
      >T.A and A.T-->C.G transversions by aromatic nitrogen mustards.

PMID- 9654243
TI  - An automated method for discriminating aneugen- vs. clastogen-induced
      micronuclei.
AB  - A flow cytometric (FCM) procedure for quantitating micronucleated reticulocytes
      in mouse peripheral blood samples was evaluated for its ability to discriminate
      between aneugen- and clastogen-induced micronuclei (MN). In this experiment,
      BALB/c mice were injected with 0.9% saline, the model clastogen methyl
      methanesulfonate (100 mg/kg bw) or the aneugen vincristine (0.2 mg/kg bw).
      Peripheral blood samples were collected 48 hr after injection and were
      subsequently fixed and stained for flow cytometric analysis. The staining method
      utilized FITC-conjugated anti-CD71 to differentially label reticulocytes, and the
      nucleic acid dye propidium iodide to resolve erythrocyte populations with and
      without micronuclei. The frequency of micronucleated reticulocytes was determined
      by analyzing 10,000 total reticulocytes per blood sample. A second analysis was
      performed on each sample whereby the propidium iodide associated fluorescent
      signals of 250 MN were collected and graphed as a single-parameter histogram. The
      histogram statistic "median channel" was recorded for each sample and provided a
      quantitative description of MN distribution according to DNA content.
      Cumulatively, the results of this study suggest that 1) flow cytometry can be
      employed to measure the incidence of MN resulting from clastogenic or aneugenic
      activity, and 2) MN resulting from aneugens can be discriminated from those
      arising spontaneously or from clastogen treatment based on flow cytometric
      analysis of DNA content.

PMID- 9654244
TI  - Comparative genotoxicity of quinolone and quinolonyl-lactam antibacterials in the
      in vitro micronucleus assay in Chinese hamster ovary cells.
AB  - The in vitro micronucleus assay is gaining increased attention as a potential
      alternative to the standard in vitro metaphase analysis assay. In particular, the
      in vitro micronucleus assay has been proposed as a useful method for chemicals
      that induce both structural and numerical chromosome alterations, such as DNA
      gyrase/topoisomerase inhibitors. In this study, we compared the micronucleus
      inducing activity of quinolonyl-lactam antibacterials that inhibit DNA-gyrase and
      bind to penicillin-binding proteins relative to the activity of structurally
      related quinolone antibacterials that also inhibit DNA-gyrase. All of the
      quinolones that were structurally related to the quinolonyl-lactams were
      cytotoxic and induced large increases in the frequency of micronucleated
      binucleated cells (MNBC) at concentrations between 0.02 and 0.16 mM. These
      changes were larger than those seen with the commercial quinolones, ciprofloxacin
      (cytotoxic at > or = 0.57 mM and MNBC at > or = 0.3 mM) and nalidixic acid
      (cytotoxic at 1.8 mM and no MNBC up to this dose). In contrast, the quinolonyl
      lactams were not cytotoxic up to 1.0 mM concentrations and induced either no MNBC
      or a low frequency of MNBC at higher concentrations compared to the quinolones.
      Quinolonyl-lactams appear to be less cytotoxic and genotoxic than structurally
      related quinolones. These results add to the growing database on the in vitro
      micronucleus assay in general, and more specifically to the relatively small
      database for the in vitro micronucleus assay in Chinese hamster ovary cells.

PMID- 9654245
TI  - Lead and mercury mutagenesis: role of H2O2, superoxide dismutase, and xanthine
      oxidase.
AB  - It has been suggested that reactive oxygen intermediates (ROIs) may have a role
      in the genotoxic effects of lead (Pb2+) and mercury (Hg2+), but there have not
      been any definitive studies demonstrating a causal relationship between the
      induction of ROIs by these metals and mutagenesis. We previously demonstrated,
      using the transgenic Chinese hamster ovary cell line AS52, that low
      concentrations (0.1-1 microM) of Pb2+ and Hg2+ are mutagenic. In the present
      study, using a novel histochemical computer-enhanced image analysis technique, we
      demonstrate that Pb2+ and Hg2+ induce the formation of H2O2 in AS52 cells by at
      least two distinct mechanisms. One is characterized by the rapid induction of
      H2O2 following treatment of cells with concentrations of Pb2+ or Hg2+ below 0.8
      and 1 microM, respectively, while the second occurs in AS52 cells treated with
      concentrations of Pb2+ or Hg2+ greater than 0.8 and 1 microM, respectively. Pb2+
      and Hg2+ (0.1-1 microM) had no effect on the activities of partially purified
      catalase, glutathione peroxidase, or glutathione reductase, important enzymes
      involved with antioxidant defense, but these metals stimulated the activities of
      copper-zinc superoxide dismutase (CuZn-SOD) and xanthine oxidase (XO).
      Allopurinol (50 microM), a specific inhibitor of xanthine oxidase, inhibited the
      induction of H2O2 by Pb2+ (0.8-1 microM) and Hg2+ (1 microM) and also inhibited
      Pb2+- and Hg2+-induced mutagenesis. These results demonstrate that Pb2+ and Hg2+
      disrupt the redox status of AS52 cells by enhancing the activities of CuZn-SOD
      and XO. Furthermore, the results of these studies also demonstrate that there is
      a causal relationship between the induction of H2O2 by these metals and
      mutagenesis.

PMID- 9654246
TI  - S-oxygenation of thiourea results in the formation of genotoxic products.
AB  - Thiourea (TU) is a thyroid carcinogen which has previously been shown to cause
      genotoxicity in various test systems in vitro and in vivo. The mechanism
      underlying these effects has not yet been elucidated. The present study addressed
      the question of whether the formation of oxidized products of TU might be
      involved in genotoxicity. Chemical oxidation of [14C]TU with hydrogen peroxide in
      the presence of calf thymus DNA resulted in the formation of [14C]formamidine
      sulfinate ([14C]FASA), [14C]cyanomide, and [14C]urea and in covalent binding of
      radioactivity to the DNA. Incubation of V79 Chinese hamster cells with 10-20 mM
      TU for 18 hr but not for 3 hr, increased the frequency of micronuclei to a slight
      extent. In cells depleted of glutathione, which can prevent the oxidation of TU,
      micronucleus induction by TU was more pronounced and detectable both after 3 and
      18 hr of incubation. Exposure of the cells to 1.25 to 10 mM FASA for 3-5 hr
      induced micronuclei, DNA repair synthesis, and gene mutations in the cells.
      Flavin-containing monooxygenase (FMO], an enzyme known to catalyze the S
      oxygenation of TU in liver, could not be detected in the postmitochondrial
      supernatant (S-9) of the V79 cells. There is evidence, however, that TU can
      easily autoxidize to S-oxygenated products. Both FASA and TU caused a slight
      induction of DNA repair synthesis in cultured rat hepatocytes, but FASA was
      active at lower concentrations than TU. Cyanamide did not elicit repair. The
      finding that FASA, a product of both the nonenzymatic and the enzymatic S
      oxygenation of TU, is genotoxic in cultured mammalian cells provides for the
      first time a hypothesis to explain the genotoxicity of TU.

PMID- 9654247
TI  - Comparison of sensitivity to methyl methanesulphonate among tadpole developmental
      stages using the alkaline single-cell gel electrophoresis (comet) assay.
AB  - In a previous study, we demonstrated that tadpoles are suitable organisms for
      monitoring small bodies of water (e.g., creeks, ponds, and drainage ditches) for
      genotoxicity using the alkaline single-cell gel DNA electrophoresis (SCG) or
      "comet" assay [Ralph and Petras, 1997]. This approach involves detection, under
      alkaline conditions, of cell DNA fragments which on electrophoresis migrate from
      the nuclear core, resulting in a "comet with tail" formation. In this initial
      study, most of the tadpoles collected were in the early stages of larval
      development, but this is not always possible. The present study evaluated the
      sensitivity of tadpoles, at different stages of larval development, to a range of
      concentrations of the genotoxicant methyl methane-sulphonate (MMS). Four specific
      phases of Rana clamitans (green frog) larval development were examined: first
      year limbless tadpoles (Stage I as defined by Taylor and Kollros [1946]), second
      year limbless tadpoles (Stages II-III), second-year tadpoles with only hindlimbs
      (Stages X-XVIII), and second-year tadpoles with all four limbs evident and a tail
      undergoing resorption (Stages XXII-XXIII). Twenty-four hour exposures to MMS of
      tadpoles in the three earliest phases produced a significant (P < 0.01) added
      variance component among tadpoles for DNA damage and there were significant
      increases (P < 0.05) in the length:width ratios of the DNA patterns at
      concentrations as low as 1.56 mg/I. However, tadpoles in the last phase studied
      (both pairs of limbs present) showed no significant (P > 0.05) added variance
      component and no significant increases (P> 0.05) in DNA damage upon exposure to
      any of the MMS doses tested. A nested ANOVA indicated that, for each of the
      tested concentrations of MMS, but not the dechlorinated water control, there was
      significant heterogeneity (P < 0.05) in DNA damage when tadpoles of all four
      phases studied were compared. However, when tadpoles of the lost phase of
      development were removed from the comparison, there was no significant
      heterogeneity (P > 0.05) among tadpoles of the remaining three phases. Possible
      reasons for this insensitivity to MMS as animals enter the metamorphic climax
      were considered. The results indicate that pooling of the early tadpole phases of
      R. clamitans for SCG environmental genotoxicity biomonitoring is acceptable.

PMID- 9654248
TI  - Unicellular green alga Chlamydomonas reinhardtii as an activation system for 2
      aminofluorene.
AB  - Despite the promutagenic/procarcinogenic potential, polycyclic aromatic amines
      are widely spread in the environment. Biotransformation of the polycyclic
      aromatic amine 2-aminofluorene (2-AF) was proved in mammals and higher plants.
      The algal cell/microbe coincubation assay is an additional system that
      complemented those proved in mammals and higher plants, useful for detection and
      conversion of environmental promutagens, mainly in aquatic environments. The
      unicellular green algae may be a good activating system in coincubation assays in
      that the algal cells exist as a natural system. To increase the effectiveness of
      this metabolizing system, different modifications of the standard experimental
      procedure were conducted. Algae can accumulate and metabolize promutagenic
      pollutants, some of which may differ from those activated by the animal microsome
      metabolizing system (S9 mix) and by the plant cell/microbe coincubation assay. 2
      AF was activated in the algal cell/ microbe coincubation assay in which wild-type
      Chlamydomonas reinhardtii cells were used as an activating system and the
      bacteria Salmonella typhimurium TA98, YG1024, and yeast Saccharomyces cerevisiae
      D7 as the genetic indicator organisms. It was converted to the mutagenic
      product(s) for the strain YG1024, but the strain TA98 did not exhibit any
      increase in the mutant yield of His+ revertants. Consequently, metabolites from 2
      AF are substrates for O-acetyltransferase. A direct comparison of algal 2-AF
      activation with mammalian activation system (S9 mix) proved the higher activity
      of mammalian microsome system (S9 mix). After the combination of both activation
      systems, a slight synergetic effect was found. Although the genetic endpoints
      induced by 2-AF using both modifications of the algal cell/S. cerevisiae
      coincubation assay and those obtained in intact yeast cells were similar at the
      equitoxic concentrations, 2-AF activation by the algal supernatant slightly
      increased the genetic endpoints studied.

PMID- 9654249
TI  - Biotransformation of several structurally related 2B compounds to reactive
      metabolites in the somatic w/w+ assay of Drosophila melanogaster.
AB  - Biotransformation of several structurally related 2B compounds to reactive
      metabolites was evaluated in the somatic w/w+ assay of Drosophila melanogaster.
      Chemicals tested were the dichlorinated alkanes dichloromethane (DCM), 1,2
      dichloroethane (DCE), and 1,3-dichloropropane (DCP); the thiouracil derivatives 5
      methyl, 2-thiouracil (5M2TU), 6-methyl, 2-thiouracil (6M2TU), and 5-propyl, 2
      thiouracil (5P2TU); and the plastic monomer styrene (STY) and its metabolite
      styrene 7,8-oxide (SO). The tester strains used consisted of one wild-type
      insecticide-susceptible (IS) laboratory strain (Leiden-S, ST), and two
      insecticide-resistant (IR) strains (Hikone-R, HK, and Haag-R, HG). The latter
      have high cytochrome P450-dependent bioactivation capacities. Drosophila larvae
      heterozygous for the wild-type report gene w+ were exposed chronically to at
      least three different exposure doses of each compound. A total of 53,694 eyes
      were analyzed. A positive genotoxic activity was obtained for DCM and for 6M2TU
      at all exposure doses and genotypes analyzed, and for SO in the IR strains HK-R
      and HG-R. An overall weakly recombinagenic response was shown by DCE and 5M2TU.
      The chemicals DCP, 5P2TU, and STY proved to be overall negative in IR as well as
      in IS strains, and SO was negative in the standard stock. Biotransformation
      mediated by cytochrome P450 monoxigenases to reactive metabolites is discussed.

PMID- 9654250
TI  - Mutagenicity and clastogenicity of gas stove emissions in bacterial and plant
      tests.
AB  - The aim of this research was to study the gaseous and particulate emissions of
      genotoxic substances during cooking with two types of methane stoves (a new one
      and an old one). The particulates were sampled both with a cascade impactor air
      sampler and an impinger with ice trap and analyzed by two bacterial mutagenicity
      tests (Ames and Kado tests) and by HPLC for polycyclic aromatic hydrocarbons
      (PAH). Gaseous emissions were studied in situ using the Ames test, a
      clastogenicity plant test (Tradescantia-micronucleus test), and in an automated
      system for chemical analyses. Clear indirect mutagenicity was found only with the
      Kado test (TA98-S9) in extracts of particulates emitted from the old methane
      stove and collected with the impinger. Similar mutagenicity (TA98+S9) was also
      found for the finest fraction of particulates (<0.5 um) collected from both
      stoves. Gaseous emissions of both stoves caused clastogenicity in the in situ
      experiments with the Tradescantia-micronucleus test. The physico-chemical
      analyses of the emissions showed also the presence of very fine particulates and
      trace amounts of PAH. The exposure of these genotoxins could be particularly
      important for occupationally exposed individuals in homes and businesses and for
      susceptible subjects living indoors for long periods (infants, children, the
      sick, and the elderly).

PMID- 9654251
TI  - Facing up to the acute coronary syndromes.

PMID- 9654252
TI  - How should doctors respond to the GMC's judgments on Bristol?

PMID- 9654253
TI  - Adjuvant IFN alpha2 therapy of melanoma.

PMID- 9654254
TI  - Genetic influence on HDL cholesterol.

PMID- 9654255
TI  - Antithrombotics for left-ventricular impairment?

PMID- 9654256
TI  - Randomised trial of interferon alpha-2a as adjuvant therapy in resected primary
      melanoma thicker than 1.5 mm without clinically detectable node metastases.
      French Cooperative Group on Melanoma.
AB  - BACKGROUND: Owing to the limited efficacy of therapy on melanoma at the stage of
      distant metastases, a well-tolerated adjuvant therapy is needed for patients with
      high-risk primary melanoma. Our hypothesis was that an adjuvant treatment with
      low doses of interferon alpha could be effective in patients with localised
      melanoma. METHODS: After resection of a primary cutaneous melanoma thicker than
      1.5 mm, patients without clinically detectable node metastases were randomly
      assigned to receive either 3x10(6) IU interferon alpha-2a, three-times weekly for
      18 months, or no treatment. The primary endpoint was the relapse-free interval.
      FINDINGS: 499 patients were enrolled, of whom 489 were eligible. When used as
      part of a sequential procedure, interferon alpha-2a was of significant benefit
      for relapse-free interval (p=0.038). A long-term analysis, after a median follow
      up of 5 years, showed a significant extension of relapse-free interval (p=0.035)
      and a clear trend towards an increase in overall survival (p=0.059) in interferon
      alpha-2a-treated patients compared with controls. There were 100 relapses and 59
      deaths among the 244 interferon alpha-2a-treated patients compared with 119
      relapses and 76 deaths among the 245 controls. The estimated 3-year-relapse rates
      were 32% in the interferon alpha-2a group and 44% in controls; the 3-year death
      rates were 15% and 21%, respectively. Only 10% of patients experienced WHO grade
      3 or 4 adverse events. Treatment was compatible with normal daily life.
      INTERPRETATION: Adjuvant therapy of high-risk melanoma with low doses of
      interferon alpha-2a for 18 months is safe and is beneficial when started before
      clinically detectable node metastases develop.

PMID- 9654257
TI  - DeltaF508 heterozygosity in cystic fibrosis and susceptibility to asthma.
AB  - BACKGROUND: Cystic fibrosis is a recessive disorder mainly characterised by lung
      disease. We tested the hypothesis that individuals heterozygous for the common
      cystic fibrosis deltaF508 mutation are at risk of obstructive pulmonary disease.
      METHODS: We studied a cross-sectional sample from the general population of
      Copenhagen, Denmark, aged 20 years and older. We did spirometry to measure forced
      expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), and did
      genotyping on blood samples of 9141 individuals. We asked all participants
      whether they had asthma, and asked for information on smoking and other factors
      that could have contributed to obstructive pulmonary disease. FINDINGS: We
      identified 250 carriers of the deltaF508 mutation (2.7% [95% CI 2.5-3.1]). 9% of
      carriers reported having asthma compared with 6% of non-carriers (p=0.04). The
      odds ratio for asthma in participants heterozygous for deltaF508 mutation was 2.0
      (1.2-3.5, p=0.02). Furthermore, among individuals with airway obstruction, the
      percentage predicted FEV1 and FVC were significantly lower in participants
      heterozygous for deltaF508 than in non-carriers (49 vs 58%, p=0.004; and 70 vs
      82%, p<0.001, respectively), mainly due to an effect in those with self-reported
      asthma. INTERPRETATION: Cystic fibrosis deltaF508 heterozygosity may be over
      represented among people with asthma and seems to be associated with decreased
      pulmonary function in people with airway obstruction who also have asthma.

PMID- 9654258
TI  - Relation between laboratory test results and histological hepatitis activity in
      individuals positive for hepatitis B surface antigen and antibodies to hepatitis
      B e antigen.
AB  - BACKGROUND: Hepatitis B surface antigen (HBsAg) and antibodies to hepatitis B e
      antigen (anti-HBe) commonly coexist, and laboratory tests are often requested to
      assess histological hepatitis activity. An optimum panel of tests has not been
      found and the usefulness of hepatitis B virus (HBV) DNA assays in this context
      has not been established. We assessed various blood tests to find which best
      predicted hepatitis activity. METHODS: Routine plasma biochemical liver tests and
      serum HBV DNA (hybridisation and PCR assays) were assessed prospectively in 123
      patients positive for HBsAg and anti-HBe. We scored histological hepatitis
      activity (hepatitis activity index) and determined whether chronic active
      hepatitis (chronic hepatitis with portal and periportal lesions) was present. We
      analysed the relation between laboratory data and the hepatitis activity index or
      risk of chronic active hepatitis by multiple regression and multiple logistic
      regression, respectively. FINDINGS: The analyses provided models for predicting
      either the hepatitis activity index or the risk of chronic active hepatitis.
      Aspartate aminotransferase was the most important test in the two models. The
      contribution of HBV DNA and other assays, especially alanine-aminotransferase
      activity, were of no practical importance. INTERPRETATION: Because screening by
      aspartate-aminotransferase activity could not be improved by the addition of
      other assays or HBV DNA, patients positive for HBsAg and anti-HBe could be
      screened for chronic active hepatitis with a single assay and counselling of
      patients can be improved if proper reference values are used.

PMID- 9654259
TI  - Beta-glucocerebrosidase gene locus as a link for Gaucher's disease and familial
      hypo-alpha-lipoproteinaemia.
AB  - BACKGROUND: Gaucher's disease is the most common lysosomal storage disorder,
      caused by deficiency of glucocerebrosidase resulting from homozygosity for any of
      several mutations of the glucocerebrosidase gene locus. Affected people have
      decreased concentrations of LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C).
      We assessed the association between mutations in the glucocerebrosidase locus and
      hypo-alpha-lipoproteinaemia. METHODS: We studied 258 people from 43 unrelated
      Spanish families. 57 participants were affected, 137 were non-affected carriers,
      and 64 were non-carriers. We determined glucocerebrosidase genotypes and measured
      plasmid lipids, apolipoproteins A-I, B, and E, and leucocyte glucocerebrosidase
      activity. FINDINGS: The most common glucocerebrosidase mutations were N370S
      (45%), L444P (23%), and G377S (5%). Deletions and recombinants accounted for
      another 5%, and point mutations in exons 5, 6, 9, and 10 were present in 12%.
      Affected participants had lower LDL-C and HDL-C concentrations than non-affected
      carriers (p<0.001) and non-carriers (p<0.001). HDL-C values were also
      significantly different between the non-affected carriers and non-carriers.
      Mutations at this locus may account for as much as 19.5% of the genetic
      variability in HDL-C in the population studied. INTERPRETATION: Heterozygosity
      for these mutations at the glucocerebrosidase locus does not result in clinical
      expression of Gaucher's disease but can decrease HDL-C concentrations. Given the
      high frequency of these mutations, the glucocerebrosidase locus might lead to
      familial low alpha-lipoproteinaemia in up to 2% of the general population and be
      one of the most common known genetic causes of HDL-C.

PMID- 9654260
TI  - Death from heroin overdose: findings from hair analysis.
AB  - BACKGROUND: Morphine analysis of hair is used in forensic toxicology to study the
      addiction history of heroin addicts. To clarify the features underlying fatal
      heroin intake, we measured hair morphine content in a group of deceased heroin
      addicts, to verify a possible correlation between fatal heroin overdoses and the
      addiction behaviour of these individuals before death. METHODS: 91 deaths were
      attributed to heroin overdose in Verona, Italy, in 1993-96. We analysed the hair
      of 37 of these individuals, and of 37 active heroin addicts, 37 former heroin
      users abstinent from the drug for several months, and 20 individuals with no
      evidence of exposure to opioids. From each individual, a hair sample of about 150
      mg was analysed by RIA and high-performance liquid chromatography, to measure the
      morphine content. FINDINGS: The mean morphine content in the hair of the addicts
      who had died was 1.15 ng/mg (SD 2.35 ng/mg; range 0-12.25 ng/mg) compared with
      6.07 ng/mg (4.29; 1.15-17.0) in the active heroin addicts, 0.74 ng/mg (0.93; 0.10
      3.32) in the abstinent former addicts, and values below the detection limit in
      the non-exposed group. Hair morphine content among those who had died was
      significantly lower than that in active heroin consumers (p<.00001), but not
      significantly different from that in the former addicts (p=0.978).
      INTERPRETATION: Although our findings may be subject to selection bias, since
      suitable hair samples were available for only 37 of the 91 addicts who had died,
      these findings support the theory of high susceptibility to opioid overdose after
      periods of intentional or unintentional abstinence, due to loss of tolerance.
      Medical staff running detoxification programmes should be aware of the risk
      inherent in relapse to heroin after a period of abstinence. Moreover, occasional
      heroin use without a build-up of tolerance could also give a high risk of
      overdose.

PMID- 9654261
TI  - A 35-year-old bricklayer with hemimyoclonic jerks.

PMID- 9654262
TI  - Rates of first measles-mumps-rubella immunisation in Wales (UK)

PMID- 9654263
TI  - Clinically occult pelvic-vein thrombosis in cryptogenic stroke.

PMID- 9654264
TI  - Sodium antimony gluconate, amphotericin, and myocardial damage.

PMID- 9654265
TI  - Rhabdomyolysis due to interaction of simvastatin with mibefradil.

PMID- 9654266
TI  - Raised plasma soluble Fas and Fas-ligand in alcoholic liver disease.

PMID- 9654267
TI  - Prognostic value of Th1/Th2 ratio in rheumatoid arthritis.

PMID- 9654268
TI  - Salivary urate in gout, exercise, and diurnal variation.

PMID- 9654269
TI  - Uncoupling protein-3 expression in skeletal muscle and free fatty acids in
      obesity.

PMID- 9654270
TI  - C282Y mutation in HFE (haemochromatosis) gene and type 2 diabetes.

PMID- 9654272
TI  - UK "Bristol case" doctors found guilty of misconduct.

PMID- 9654271
TI  - Somesthetic aura: the experience of "Alice in Wonderland".

PMID- 9654273
TI  - "Personalised" drug therapy could be near.

PMID- 9654274
TI  - Mike Dexter: a forthright view of biomedical science.

PMID- 9654275
TI  - Bad blood in US genome research.

PMID- 9654276
TI  - Hollow celebration of 50 years of human-rights campaigning.

PMID- 9654277
TI  - Kindling a conscience for the biotech industry.

PMID- 9654278
TI  - Intracoronary stenting.

PMID- 9654279
TI  - The case for allowing kidney sales. International Forum for Transplant Ethics.

PMID- 9654280
TI  - Mission-oriented research: a case study.

PMID- 9654281
TI  - If children's lives are precious, which children?

PMID- 9654282
TI  - Locking the door: US imprisonment of asylum seekers.

PMID- 9654283
TI  - Forensic medicine: international criminal tribunals and an international criminal
      court.

PMID- 9654284
TI  - Vascular complications associated with use of HIV protease inhibitors.

PMID- 9654285
TI  - Vascular complications associated with use of HIV protease inhibitors.

PMID- 9654286
TI  - Vascular complications associated with use of HIV protease inhibitors.

PMID- 9654287
TI  - Vascular complications associated with use of HIV protease inhibitors.

PMID- 9654288
TI  - Meta-analysis.

PMID- 9654289
TI  - Effectiveness of pneumococcal vaccine.

PMID- 9654290
TI  - Effectiveness of pneumococcal vaccine.

PMID- 9654291
TI  - Prophylactic antibiotics before insertion of intrauterine devices.

PMID- 9654292
TI  - Intrauterine devices in HIV-1-infected women.

PMID- 9654293
TI  - Oral melatonin in neurologically disabled children.

PMID- 9654294
TI  - Oral melatonin in neurologically disabled children.

PMID- 9654295
TI  - Japanese encephalitis virus and poliomyelitis-like illness.

PMID- 9654296
TI  - Opiates for sickle-cell crisis?

PMID- 9654297
TI  - Opiates for sickle-cell crisis?

PMID- 9654298
TI  - Opiates for sickle-cell crisis?

PMID- 9654299
TI  - Catechol-O-methyltransferase inhibitors in Parkinson's disease.

PMID- 9654300
TI  - Catechol-O-methyltransferase inhibitors in Parkinson's disease.

PMID- 9654301
TI  - MERLIN and malaria epidemic in north-east Kenya.

PMID- 9654302
TI  - Antiepileptic drugs in developing countries.

PMID- 9654303
TI  - The RAGE litigation. Radiation Action Group Exposure.

PMID- 9654304
TI  - Scaling prison walls.

PMID- 9654306
TI  - Surgical invasion and infection conference: introductory remarks.

PMID- 9654307
TI  - A microbiologist's view of factors contributing to infection.
AB  - Why some patients develop postoperative surgical wound infection and others do
      not remains a mystery. There are many risk factors for infection, and
      mathematical scoring systems are often good predictors of infection; yet, some
      patients with a plethora of risk factors fail to develop surgical site
      infections. Even patients with established abdominal infection do not
      automatically develop wound infection. Early experimental work, now confirmed in
      the clinical setting, dictates that bacteria must be in the wound to cause
      infection; the minimal infecting dose will depend on the environmental conditions
      in the wound. The presence of foreign bodies, trauma, hematoma, etc., will
      enhance the effect of the inoculum; therefore, surgical debridement and careful
      surgery are necessary to reinforce the host defenses. Some bacteria, e.g.,
      Staphylococcus aureus and Streptococcus pyogenes, have a greater propensity to
      cause infection, so extensive infection-control practices are necessary to
      prevent or contain these pathogens. To minimize the risk of surgical site
      infection, individual patient risk factors must be identified and modified
      whenever possible. The patient should be prepared for the operation and
      appropriate skin antiseptics should be used on the operative site. The patient
      should be considered for perioperative antibiotic prophylaxis and, if
      appropriate, bowel preparation should be carried out. Care and attention to the
      theater operating environment is important, especially for cases in which
      airborne transmission of bacteria should be controlled, e.g., ultraclean air
      systems for implant surgery. In elective surgery, the source of bacteria that
      cause infection is either the patient's normal flora (e.g., skin or bowel), i.e.,
      endogenous, or the surgical staff or environment, i.e., exogenous. Surgical
      expertise and theater discipline are essential components in the fight against
      surgical sepsis.

PMID- 9654308
TI  - Antibiotic prophylaxis.
AB  - During the past 30 years, antibiotic prophylaxis has proved of enormous efficacy
      in reducing the incidence of surgical wound infections, postoperative morbidity
      and mortality, the duration of the postoperative period, and the overall cost of
      surgical treatment. In this paper, the timing and route of administration of
      antibiotic prophylaxis as well as the dosage and duration, the indications for
      antibiotic prophylaxis, the importance of the alterations of the delayed
      hypersensitivity response, and the value of antibiotic prophylaxis for prevention
      of postoperative septic complications in anergic patients are analyzed. The
      possibility of combining antibiotic prophylaxis with immunoprophylaxis for high
      risk patients is also analyzed.

PMID- 9654309
TI  - Contemporary wound infection surveillance issues.
AB  - Contemporary wound infection surveillance is inexact. Tracking down suspicious
      incisions with maximal accuracy to isolate the subset of healing failures
      attributable to established tissue invasion by infecting pathogens has a solitary
      purpose: to learn how to improve one aspect of surgical practice. Wound infection
      is always the result of complex, probabilistic interplay of numerous concealed
      variables. A wound infection rate, whether determined for a hospital, a
      specialty, a risk class, an operation type, or a surgeon, only approximates a
      degree of failure to achieve one kind of surgical perfection. Interpretation of
      any rate will be flawed if issues of accuracy and meaning are suppressed.
      Gathering and revealing circumstances of individual infections may heuristically
      affect surgical teams. Interpretation of surveillance wound infection rates,
      infection rate comparisons to standards as a means of performance measurement,
      and particularly the meaning of rate changes over time in a hospital are matters
      of more than academic importance. Given current health care reform and a
      widespread fascination with industrial process-improvement philosophy, wound
      infection surveillance programs may be natural test platforms for probing
      surgical relevance of several quality-improvement methodologies. It is not a
      trivial fact that wound infection shares important prototypical features with
      most contemporary surgical care process flaws: rare, random, multifactorial in
      cause, costly, and impossible to uniformly preclude or predict.

PMID- 9654310
TI  - Ventilator-associated bacterial pneumonia: challenges in diagnosis, treatment,
      and prevention.
AB  - Ventilator-associated pneumonia (VAP) is a common infection in intensive care
      unit patients that results in high mortality and morbidity and increased duration
      of hospital stay. Clinical diagnostic methods are sensitive, but lack
      specificity. Quantitative analysis of specimens from the lower respiratory tract
      increases specificity. Bacteria causing VAP may originate from the patient's
      endogenous flora, other patients or hospital personnel, or from environmental
      sources. Aspiration or direct inoculation are the major routes of bacterial entry
      into the lower respiratory tract. The bacterial inoculum and host response in the
      lung are important factors for pathogenesis. Late-onset nosocomial pneumonia is
      often caused by Pseudomonas aeruginosa, Acinetobacter species, and Staphylococcus
      aureus. Streptococcus pneumoniae and Haemophilus influenzae, however, are the
      more common pathogens in early-onset disease. Oropharyngeal and gastric
      colonization with bacteria, cross-infection, as well as the indiscriminate use of
      antibiotics or invasive devices substantially increase the risk of VAP. An
      understanding of the epidemiology and pathogenesis of VAP, along with
      implementation of appropriate preventive measures, are needed to decrease the
      incidence, morbidity, and mortality associated with VAP.

PMID- 9654312
TI  - Antibiotic prophylaxis in clean surgery: does it work? Should it be used if it
      does?
AB  - Perioperative antibiotic prophylaxis has been demonstrated to prevent
      postoperative wound infection after clean surgery in a majority of clinical
      trials with sufficient power to identify a 50% reduction in risk. The low risk of
      infection after many clean procedures requires studies of more than 1,000
      procedures (sometimes many more) to detect such reductions reliably. This is a
      serious obstacle to performing conclusive tests of efficacy, and it all but
      precludes use of conventional clinical trials to identify optimal regimens.
      Regimens that have been shown to be effective have usually been those with
      efficacy against Staphylococcus aureus and other pathogens that may be carried in
      the nares or on the skin. In addition, relatively long half-life in the serum and
      low cost are important considerations. Cefazolin is a good prophylaxis agent for
      many clean surgical procedures, although special characteristics of the
      procedure, increased likelihood of antimicrobial resistance, or antibiotic
      utilization concerns may make other agents more suitable in specific situations
      The decision to use perioperative antibiotic prophylaxis for clean surgical
      procedures depends not only on its efficacy, but also on the cost of preventing
      infection. Few cost-benefit analyses have been performed, especially for
      procedures in which prophylaxis has been least used. To perform such analyses, it
      will be necessary to acquire information that is currently lacking for many
      procedures. This includes the risk and cost of postoperative infection, adverse
      reactions to the prophylaxis agent, and increased antimicrobial resistance; in
      addition, detailed information is needed on infection-associated costs of medical
      care, lost productivity, and the value that the infected person places on
      avoiding infection. For many procedures, timely use of an appropriate antibiotic
      is the single most effective infection prevention method that can be implemented
      and monitored on a broad scale. These features make it amenable to adoption as a
      subject of continuous quality improvement activities. To accomplish this, it is
      necessary to articulate standards of care clearly so that systems to support the
      intended goal can be developed. Both the standards and the support systems can be
      tailored to specific surgical situations and to the values of providers and
      patients.

PMID- 9654311
TI  - The role of oral antimicrobials for the management of intra-abdominal infections.
AB  - BACKGROUND: Oral therapy for patients with complicated intra-abdominal infections
      has been very limited because those patients are frequently ill and need surgery.
      In addition, at the time of diagnosis and initial treatment, the infection is
      often accompanied by ileus, gastrointestinal tract function is frequently
      unknown, and many patients cannot tolerate oral intake. The use of oral
      antimicrobials in this setting is a recent advance resulting from the
      availability of agents with good tissue pharmacokinetics and potent aerobic gram
      negative activity. This is the first prospective blinded study of oral therapy to
      provide data on the characteristics of patients eligible for oral treatment and
      the consequences of such treatment. STUDY DESIGN: In blinded fashion, patients
      with complicated intra-abdominal infections were randomized to either i.v.
      ciprofloxacin plus metronidazole or i.v. imipenem throughout their treatment
      course, or i.v. ciprofloxacin plus metronidazole and treatment with oral
      ciprofloxacin plus metronidazole when oral feeding was resumed (CIP/MTZ
      i.v./oral). Physicians could switch the patient to oral therapy between 3 and 8
      days after the start of i.v. treatment. RESULTS: One hundred fifty-five of 330
      (47%) patients were switched to active or placebo oral therapy. Patients who
      received i.v./oral therapy were treated, overall, for an average of 8.6 +/- 3.6
      days, with an average of 4.0 +/- 3.0 days of oral treatment. Of 46 CIP/MTZ
      i.v./oral patients (active oral arm), treatment failure occurred in 2 patients
      (4%) compared with 41 patients (23%) who were not switched to oral agents. No
      patient or disease features, such as Acute Physiology and Chronic Health
      Evaluation II score, severity of illness at study entry, organ source of
      infection, or duration of treatment were identified as predictors of conversion
      to oral treatment. CONCLUSIONS: In this first prospective examination of
      sequential i.v./oral therapy for complicated intra-abdominal infections,
      conversion to oral therapy with ciprofloxacin plus metronidazole appears as
      effective as continued i.v. therapy for patients able to tolerate oral feedings.
      Patients who can tolerate oral intake may be treated with appropriate oral
      antimicrobials and are not at any significant increased risk for failure.

PMID- 9654313
TI  - Bacterial colonization of prosthetic devices and measures to prevent infection.
AB  - Prosthetic devices are used extensively in surgical practice. This includes
      devices used on a temporary, intermittent, and long-term basis. In addition to
      problems with biocompatibility, the main health care issue concerning prostheses
      is the elevated risk of infection and the current inability to effectively
      prevent and treat such infections. An appreciation of microbial biofilm
      development has drawn attention to flaws in diagnosis and led to new methods to
      attack the problem. Future remedies will likely involve utilization of new
      biomaterial designs and application of either highly potent antimicrobials or
      agents used in combination that penetrate biofilms and eradicate the organisms.

PMID- 9654314
TI  - What is the value of preventing postoperative infections?
AB  - The importance of postoperative infections depends on the frequency with which
      infection occurs as well as on the additional cost per patient with infection.
      For example, in our hospital the additional cost per patient with infection after
      hernia repair was $600, compared with $2,106 per patient with infection after
      colonic surgery. However, the total excess cost per year was similar for hernia
      surgery ($44,800) and colon surgery ($48,440). The reason is that hernia surgery
      is much more common than colon surgery. It is a general principle of clinical
      audit that the importance of problems should be defined by their frequency as
      well as their individual severity. A third important consideration is the
      likelihood that the problem can be corrected. Undue attention has been given to
      the health resource costs of postoperative infection at the expense of
      information about the intangible costs to the patient (these are nonfinancial
      costs such as pain and disability). Health resource costs are very dependent on
      medical practice variation, and comparative studies between countries reveal
      marked differences in the way that apparently similar infections are managed.
      Moreover, comprehensive audit of infection-control management often reveals
      wasteful practice, e.g, antibiotic treatment of patients who do not in fact have
      infection. Audit of postoperative infection should focus on eliminating wasteful
      practice (e.g., prophylactic antibiotics continuing > 24 hrs after surgery) as
      well as on reducing postoperative infection rates.

PMID- 9654315
TI  - Infections complicating pancreatitis: diagnosing, treating, preventing.
AB  - The most important risk factor in patients suffering from acute necrotizing
      pancreatitis is pancreatic infection, a factor that determines the course of the
      disease, its therapeutic management, and its outcome. The bacterial infection
      route is very likely via the colon. In patients with acute pancreatitis, the
      infection rate is about 40 to 70% within the first 3 wks. Bacteria most
      frequently found are those from the gastrointestinal tract: Escherichia coli,
      Pseudomonas species, Streptococcus fecalis, Enterococcus, and Staphylococcus
      aureus. Screening methods for infected necrotizing pancreatitis include fine
      needle puncture by ultrasonography or computed tomographic guidance with Gram
      staining and culture of the aspirate. We previously investigated different broad
      spectrum antibiotics with regard to their efficacy at preventing infection. This
      analysis indicated that antibiotics have different efficacy factors based on
      pharmacodynamic properties. Imipenem and quinolones, in combination with
      metronidazole, are the drugs of choice for treating or preventing pancreatic
      infection, whereas aminoglycosides do not enter the pancreas and therefore are
      not indicated. Based on increasing evidence that patients with acute necrotizing
      pancreatitis will benefit by early and appropriate antibiotic therapy, we altered
      the approach in such patients with an immediate start of antibiotic therapy
      continued for at least 14 days. We have found a reduction of the infection rate
      to 33% (11/32) in the third week after the onset of the disease. This treatment
      of the infection and the possibility of delaying operative intervention resulted
      in optimal surgical conditions. However, further prospective, controlled, and
      randomized studies are necessary to determine which antibiotics and antimycotic
      therapeutic regimens should be chosen.

PMID- 9654316
TI  - Impact of laparoscopic surgery on stress responses, immunofunction, and risk of
      infectious complications.
AB  - Open laparotomy is followed by profound changes in endocrine metabolic function
      and various host defense mechanisms, impaired pulmonary function, and hypoxemia,
      all of which may be important for the development of postoperative infectious
      complications. Laparoscopic surgery, however, leads to a reduced inflammatory
      response (C-reactive protein and interleukin-6), a reduced immunomodulatory
      response, improvement in pulmonary function, and less hypoxemia, whereas classic
      endocrine metabolic responses are less influenced or not influenced compared with
      similar open operation. The clinical implications of laparoscopic surgery on
      postoperative infectious complications have not been assessed in large-scale
      prospective, randomized studies, except in appendectomy, in which a reduced
      incidence of wound infection has been demonstrated. Data from cholecystectomy and
      colorectal surgery suggest a reduction in wound complications, whereas the sparse
      data on intraperitoneal infections and sepsis are not conclusive. Thus,
      laparoscopic surgery modifies the injury response and reduces the risk of
      infectious complications. If integrated into an accelerated rehabilitation
      program, further improvement may result. The impact of these findings on
      prophylactic antibiotic regimens cannot be assessed from available data and
      requires evaluation in prospective clinical studies.

PMID- 9654317
TI  - Predicting the need for reoperation for abdominal infection.
AB  - Abdominal infection complicating abdominal operation is a serious clinical
      problem that is subject to diagnostic delay, which is a risk factor for adverse
      outcomes. Clinical examination and laboratory and imaging modalities become more
      accurate at achieving a diagnosis once the patient becomes sicker from infection
      but cannot reliably predict the need for reoperation early in the postoperative
      course. The Abdominal Reoperation Predictive Index scoring system synthesizes
      common sense and objective measurements in an attempt to predict the need for
      reintervention before it is too late. We encourage other centers to test this
      predictor in their own patient populations.

PMID- 9654318
TI  - Therapeutic immunomodulatory approaches for the control of systemic inflammatory
      response syndrome and the prevention of sepsis.
AB  - In the sequelae of massive traumatic stress, substantial impairment of
      immunologic reactivity has been demonstrated to correlate clinically with
      increased susceptibility to serious infection. Posttraumatic immune abnormalities
      consist basically of two coexistent mechanisms: Hyperinflammation and depression
      of cell-mediated immune responses. It is our understanding that the endogenous
      ability of the organism to survive overwhelming trauma is insufficient and
      requires exogenous support to prevent the conversion from systemic inflammatory
      response syndrome to bacterial sepsis and septic shock. The objectives of
      immunomodulatory interventions, which should be started as early as possible
      after tissue destruction, include a) prevention of excessive macrophage
      stimulation via neutralization of circulating endotoxins and exotoxins with high
      doses of polyvalent immunoglobulin and soluble complement receptors, b) global
      short-term (<72 hrs) down-regulation of inflammatory monocyte/macrophage and
      polymorphonuclear neutrophil activity, and c) restoration of cell-mediated immune
      performance to overcome posttraumatic functional paralysis. Among recent
      promising strategies, the use of granulocyte-macrophage colony-stimulating
      factor, pentoxifylline, and recombinant human interleukin-13 has been suggested,
      all of them predominantly down-regulating the Mphi (monocyte/macrophage)
      inflammatory potential. Cyclooxygenase inhibitors such as indomethacin and
      thymomimetic peptides can help normalize the immunoreactivity by restoring the
      forward-regulatory pathway of cell-mediated immunity responses. The efficacy of
      interferon to reduce infection and deaths in severely injured patients has been
      assessed in clinical trials. Still other compounds, i.e., CNI-1493, interleukin
      11, tissue factor pathway inhibitors, and PGG-Glucan represent auspicious
      immunomodulatory approaches for control of posttraumatic or postoperative
      infections.

PMID- 9654319
TI  - Hypovolemic shock in pediatric patients.
AB  - Hypovolemic shock is a common disease treated in pediatric ICUs and emergency
      departments worldwide. A wide variety of etiologic factors may cause this
      disease, with the common net result of decreased intravascular volume leading to
      decreased venous return to the heart and decreased stroke volume. Inadequate
      perfusion results in impairment of delivery of nutrients and oxygen to vital end
      organs. With the advent of pediatric critical care and pediatric emergency
      medicine as specialties, deaths from hypovolemic shock have become increasingly
      rare in the United States. The physical signs of hypovolemic shock in children
      must be quickly recognized, and aggressive volume resuscitation must be
      administered before irreversible end-organ dysfunction occurs. This is best
      accomplished by large peripheral or central intravenous access, with intraosseous
      access an alternative option in the pediatric patient. The amount as well as the
      type of volume administered must be tailored for each individual patient, taking
      into account the amount of intravascular depletion and the disease state in which
      the shock has occurred. It is not uncommon for children to require large amounts
      of fluid for resuscitation, and close attention must be paid to children with
      fluid-refractory shock, who may require catecholamine and/or exogenous steroid
      support in combination with aggressive fluid resuscitation.

PMID- 9654320
TI  - Pathophysiology of cardiovascular dysfunction in septic shock.
AB  - Sepsis and septic shock are common problems in the ICU and carry a very high
      mortality. Myocardial depression is a common finding in patients with sepsis, and
      is usually reversible as the patient recovers. Both exogenous mediators, such as
      endotoxin, and endogenous cytokines, including tumor necrosis factor-alpha,
      interleukin-1beta, and interleukin-6, have been implicated as important factors
      in the pathophysiology of septic shock and the development of myocardial
      depression in sepsis. Nitric oxide has also been implicated in the
      pathophysiology of the cardiovascular response to sepsis. Better understanding of
      the roles and interactions of these substances will be necessary to develop more
      effective therapies without increasing morbidity and mortality.

PMID- 9654321
TI  - Cardiogenic shock.
AB  - The pathophysiology of cardiogenic shock in infants and children is
      multifactorial and include noncardiac as well as cardiac etiologies, both
      congenital and acquired heart disease. The management of patients in cardiogenic
      shock requires a rational approach that is based upon the underlying
      pathophysiology. The diagnosis and management of cardiogenic shock, therefore,
      requires a thorough understanding of not only the underlying pathophysiology, but
      also the diagnostic modalities used in making the diagnosis. In the pediatric
      population, echocardiography plays a pivotal role in the diagnosis and management
      of infants and children presenting with cardiogenic shock. In this article, the
      pathophysiology of cardiogenic shock and the use of echocardiography in reaching
      a differential diagnosis are discussed. In addition, the management of
      cardiogenic shock is reviewed.

PMID- 9654322
TI  - Hemorrhagic and obstructive shock in pediatric patients.
AB  - Shock in childhood is most commonly related to injury and blood loss, but
      hemodynamic compromise is occasionally caused by severe head or spinal injury,
      tension pneumothorax, myocardial injury, arrhythmias, and sepsis. Regardless of
      the cause, the initial management of the hypertensive child is establishment of a
      secure airway, maintenance of ventilation, and initiation of volume replacement
      via an adequate intravenous catheter. At the present time, crystalloid
      resuscitation with lactated Ringer's solution and buffering of acidosis with
      sodium bicarbonate is the standard approach, although in the future hypertonic
      saline solution may play a role. Hemorrhage may be classified according to the
      percentage of blood volume lost; losses in excess of 30% of blood volume (class
      III and IV hemorrhage) usually require administration of packed red blood cells
      and/or albumin as well. With appropriate management, the typical clinical signs
      of shock will be reversed and the child will demonstrate improved vital signs,
      peripheral circulation and sensorium, normalization of body temperature, reversal
      of metabolic acidosis, and resumption of normal urine output. The more aggressive
      the approach to resuscitation, the more prompt the patient's response and the
      more likely morbidity and mortality will be minimized.

PMID- 9654323
TI  - Linear and nonlinear dynamics and the pathophysiology of shock.
AB  - Rapid progress has been made in the use of linear and nonlinear time series
      analysis of heart rate and blood pressure variability as an indicator of disease
      severity and prognosis for patients in shock. Clinical and experimental studies
      have demonstrated the potential for linear and nonlinear measurements as a method
      for quantifying changes in neuroautonomic cardiovascular regulatory mechanisms.
      These measures have been demonstrated to correlate with severity of illness and
      outcome for critically ill and injured patients, including those with shock.
      These powerful mathematical techniques may allow for new insights into the
      pathophysiology of shock. In addition, these measures may also enable detection
      of early changes in neuroautonomic cardiovascular regulatory mechanisms during
      the development of shock before the onset of overt hypotension and inadequate
      tissue perfusion or may be used to assess the response to therapy. Further
      studies are needed to establish the role of these tools in clinical use.

PMID- 9654324
TI  - Reactive oxygen species in the cellular pathophysiology of shock.
AB  - Reactive oxygen species (ROS) mediate the fine balance between cellular
      physiology and pathophysiology. Accordingly it is not surprising that cellular
      redox homeostasis is disrupted by shock events related to ischemia-reperfusion
      and inflammation. ROS may initiate as well as amplify the shock cellular insult
      in a number of ways which include important contributions to inflammation as well
      as lytic and apoptotic cell death. In addition, ROS in the setting of shock
      represent important antecedents to cellular proliferation, differentiation, and
      adaptation by virtue of altered transcription and translation of antioxidant
      enzymes, stress proteins, and a variety of cytokines. It is likely that an
      eventual important biochemical therapeutic goal in the setting of shock will
      involve re-establishing cellular redox homeostasis not only to ensure cellular
      structural integrity, but also to re-establish normal secondary cellular signal
      transduction mechanisms.

PMID- 9654325
TI  - Molecular biology of septic shock.
AB  - Septic shock is a complex pathophysiologic state which often leads to multiple
      organ dysfunction, multiple organ failure, and death. This review summarizes
      current views on the molecular biology of three aspects of septic shock:
      recognition of bacterial invasion and induction of the cytokine response; genetic
      variability among humans and their predispositions toward pathologic inflammatory
      responses; and the signal transduction mechanisms which account for the transfer
      of molecular signals from cytokine receptors on the plasma membrane to cytokine
      responsive genes in the nucleus. In particular, the review summarizes the pathway
      involved in tumor necrosis factor signaling through nuclear factor-kappaB, and
      elucidates the molecular signals involved in inflammatory responses and
      apoptosis.

PMID- 9654326
TI  - Potential protective role of the heat shock response in sepsis.
AB  - The heat shock response, a primitive and highly conserved cellular defense
      mechanism, has broad protective effects against sepsis-induced injury. In various
      models of sepsis, induction of the heat shock response protects against sepsis
      induced mortality, organ injury, cardiovascular dysfunction, and apoptosis. The
      mechanisms by which the heat shock response protects against sepsis-induced
      injury are currently under investigation. One potential mechanism involves the
      ability of the heat shock response to inhibit proinflammatory responses. The heat
      shock response has been demonstrated to inhibit expression of the cytokines tumor
      necrosis factor (TNF)-alpha and interleukin (IL)-1beta. The heat shock response
      has also been demonstrated to inhibit cytokine-mediated expression of inducible
      nitric oxide synthase. Recent studies demonstrated that the heat shock response
      inhibits nuclear translocation of nuclear factor-kappaB (NF-kappaB), a
      transcription factor involved in the regulation of many proinflammatory
      responses. Heat shock response-mediated inhibition of NF-kappaB nuclear
      translocation involves stabilization of an NF-kappaB inhibitory protein called I
      kappaBalpha. The heat shock response also increases expression of I-kappaBalpha,
      thus providing another potential mechanism by which the heat shock response can
      modulate proinflammatory responses. Future studies designed to further understand
      the protective role of the heat shock response against sepsis-induced injury may
      allow for the development of rational pharmacologic agents or gene therapy
      methods to safely induce the heat shock response as a strategy to treat patients
      with sepsis.

PMID- 9654327
TI  - Recent advances in pediatric cardiopulmonary resuscitation and advanced life
      support.
AB  - The end point of uncorrected shock is cardiac arrest. Once cardiac arrest occurs,
      the outcome in children is typically poor, reflecting the fact that cardiac
      arrest does not occur until the child's physiologic reserves are exhausted.
      Despite more than 35 years of research in cardiac arrest, the optimal management
      and treatment remain uncertain. The optimal method of basic and advanced life
      support to restore cardiac function and preserve brain function is unclear, as is
      the appropriate application of pharmacologic agents to restart the heart and
      subsequently to manage postarrest shock. New techniques in basic life support
      merit evaluation in children, particularly interposed abdominal compression and
      active compression-decompression cardiopulmonary resuscitation. Epinephrine
      remains the pharmacologic agent of choice. The role of bicarbonate in the
      management of acidosis and the role of calcium in restarting the heart remain
      controversial. If and when the heart is restarted following cardiac arrest, the
      work is just beginning for the intensivist to manage the postarrest shock state.
      Dobutamine is useful in the normotensive child while epinephrine infusions are
      used to stabilize hypotensive, postarrest shock in the child.

PMID- 9654328
TI  - Nutrition and shock in pediatric patients.
AB  - Critically ill patients, including those in shock, often present with significant
      metabolic derangement in protein and energy metabolism characterized by:
      increased protein breakdown which is not suppressed by protein or energy intake;
      reprioritization of protein synthesis with increased synthesis of acute-phase
      proteins; decreased synthesis of structural proteins; and high protein turnover.
      In addition, there is also glucose and lipid intolerance. Adequate nutritional
      and metabolic support of the critically ill child under these conditions is a
      challenging endeavor. Traditionally, critically ill children have received
      nutritional requirements based on those of healthy children despite the fact that
      the critically ill population is physiologically and metabolically different.
      Furthermore, nutritional requirements in healthy children are largely based on
      limited data. With emerging knowledge of non-nutritional functions of nutrients,
      adequacy of nutritional support and requirements will eventually depend on the
      goals to be achieved: nutritional, physiologic, and/or pharmacologic.

PMID- 9654329
TI  - An international perspective on the treatment of pediatric shock: the Brazilian
      experience.
AB  - Shock in the pediatric population has many preventable causes. Treatment of
      children in shock will depend on access to health services, training of health
      personnel, availability of diagnostic procedures, monitoring, and therapeutic
      measures. Countries will differ among themselves and within themselves in the
      care provided to children developing shock. In Brazil, the majority of children
      are cared for in public hospitals, which often lack resources for basic care.
      Many children in shock do not even reach healthcare services. Investment in
      training healthcare personnel in a simplified and systematic approach to shock
      and access to equipped health services are basic to improved outcomes in the
      treatment of pediatric shock. The Brazilian experience in the treatment of
      children in shock outside hospital facilities, in the emergency department, and
      in the ICU is described.

PMID- 9654330
TI  - High ethanol tolerance in young adults is associated with the low-activity
      variant of the promoter of the human serotonin transporter gene.
AB  - Central serotonergic neurotransmission has been implicated in the aetiology of
      ethanol tolerance and dependence. Cellular expression of the serotonin
      transporter and serotonin reuptake is modulated via a polymorphic, repetitive
      element in the 5'-flanking regulatory region of the serotonin transporter gene (5
      HTTLPR). We report the association of the low-activity, short variant of the 5
      HTTLPR with high ethanol tolerance among young adults in a case-control
      association study (n = 713). The low-activity 5-HTTLPR showed a significantly
      increased allele frequency (chi2 = 7.30; df = 2; P = 0.007) and genotype
      frequency among young adults (< or =26 years) with high ethanol tolerance
      homozygous for the short allele (chi2 = 7.58; df = 1; P = 0.02). The estimated
      odds ratio for the homozygous short variant compared to the homozygous long
      variant was 2.82 (95% CI 1.30-6.11). This indicates that the low-activity 5
      HTTLPR may be involved in the neuronal mechanisms responsible for ethanol
      tolerance and dependence.

PMID- 9654331
TI  - Rat dorsal root ganglion neurones express different capsaicin-evoked Ca2+
      transients and permeabilities to Mn2+.
AB  - Capsaicin (1 microM) evoked [Ca2+]i transients in two-thirds of a Percoll
      gradient enriched population of rat dorsal root ganglion (DRG) neurones. Amongst
      the capsaicin-sensitive neurones, 68% responded to capsaicin with peak [Ca2+]i
      transients of 681 +/- 67 nM, whereas the remaining neurones gave peak [Ca2+]i
      transients of 260 +/- 84 nM. In the presence of Mn2+ in Ca2+-free medium,
      capsaicin evoked quenching of fura-2 fluorescence, due to Mn2+ influx, in a
      similar proportion of neurones. Two patterns of capsaicin-sensitive Mn2+
      quenching were observed: 72% of neurones showed rapid quenching (t1/2 of 18.3 +/-
      4.1 s), whereas the remaining neurones had low quenching rates (t1/2 of 119 +/-
      33 s). Distinct capsaicin-sensitive subpopulations of DRG neurones can thus be
      distinguished on the basis of their peak [Ca2+]i transient amplitudes, which
      appear to be associated with different rates of Ca2+ influx.

PMID- 9654332
TI  - Interactions between nociceptive and non-nociceptive afferent projections to
      cerebral cortex in humans.
AB  - We investigated the effect of a tonic discharge of muscle nociceptive afferents
      on somatosensory evoked potentials (SEPs) in humans in response to stimulation of
      non-nociceptive afferents arising from the same muscle. Conditioning nociceptive
      muscle stimulation was achieved by local injection of 50 mg levo-ascorbic acid
      (in a volume of 0.3 ml) in the body of the extensor digitorum brevis muscle
      (EDB). The test stimulus for SEPs was an electrical pulse applied to the EDB
      nerve at an intensity below the motor threshold. The main finding was that tonic
      muscle nociceptive stimulation strongly depressed the middle-latency P60-N75
      complex without modifying the size of the early P40-N50 complex of SEPs.
      Depression of the P60-N75 complex was correlated with the pain-induced loss of
      proprioception of the foot, making it plausible that this cortical complex
      reflects neuronal processes leading to perception.

PMID- 9654333
TI  - Differential uptake of dextran beads by astrocytes, macrophages and
      oligodendrocytes in mixed glial-cell cultures from brains of neonatal rats.
AB  - The present study addresses a controversy over the abilities of astrocytes to
      perform phagocytosis. Primary glial-cell cultures were prepared from the brains
      of neonatal rats and were incubated with fluorescently-labeled dextran beads
      (molecular weights approximately 10 and approximately 40 kDa). Astrocytes and
      oligodendrocytes were double-labeled by immunofluorescence staining of cell
      specific markers, and microglia by lectin histochemistry. Cells were permitted to
      take up beads for 1 h, fixed, and incubated with primary antibodies, followed by
      fluorescent secondary antibodies or fluorescently-labeled lectin. Macrophages and
      astrocytes internalized beads of both sizes. In astrocyte processes the beads
      appeared to line up along glial filaments. The results, which provide direct
      evidence for uptake of beads by astrocytes in vitro and against equally rapid, if
      any, uptake by oligodendrocytes, bear upon issues of acid/base balance and glial
      cell development and are relevant to neuropathological observations in human
      disease.

PMID- 9654334
TI  - Ontogeny of a diurnal rhythm in arylalkylamine-N-acetyltransferase mRNA in rat
      pineal gland.
AB  - Melatonin synthesis in the pineal gland of adult rats is linked to cAMP-dependent
      transcriptional and post-transcriptional regulatory mechanisms affecting its rate
      limiting enzyme, the arylalkylamine-N-acetyltransferase (AA-NAT). During
      development of the pineal gland, neuronal control gains access to the earlier
      matured cAMP-signaling pathway to shape the day-night rhythm in AA-NAT enzymatic
      activity. By semiquantitative in situ hybridization we analyzed if the
      developmental onset of a rhythmic AA-NAT activity is correlated to a temporally
      parallel onset in AA-NAT transcription. We found that AA-NAT mRNA levels in rat
      pineal gland become rhythmic at postnatal day 5. Thus, AA-NAT gene transcription
      in rat pineal gland starts to show day-night differences shortly prior to the
      appearance of a rhythmic AA-NAT activity.

PMID- 9654335
TI  - Transient expression of the vesicular monoamine transporter during development in
      the rat thalamus and cortex.
AB  - The postnatal developmental pattern of the central vesicular monoamine
      transporter-2 (VMAT2) was analyzed in the rat brain by means of quantitative
      autoradiography with a specific and high affinity ligand [3H]dihydrotetrabenazine
      ([3H]TBZOH). We show a dense expression of VMAT2 in the cortex (especially area
      17) and thalamus (particularly the dorsal lateral geniculate nucleus) at
      postnatal days 1 and 8. This pattern of VMAT2 distribution was transient since it
      was no longer observed at day 20 or in the adult rat brain where VMAT2 density
      was weak and uniform in these regions. These data suggest that monoamine
      vesicular storage participates in the early postnatal maturation of thalamus and
      cortex.

PMID- 9654336
TI  - Cannabinoid effects in basal ganglia in a rat model of Parkinson's disease.
AB  - Cannabinoid receptors in the brain are highly concentrated in the basal ganglia,
      which is in accordance with their well known effects on motor behavior. In this
      study, rats with 6-hydroxydopamine lesions of the nigrostriatal pathway were
      implanted with cannulae in the striatum, globus pallidus and substantia nigra.
      The effect of unilateral infusion of the potent cannabinoid agonist CP55,940 on
      turning behavior was studied for each structure. Lesioned animals responded to
      intrapallidal and intrastriatal administration of the cannabinoid in a manner
      that was similar to that of unlesioned animals. However, lesioned animals showed
      greater contralateral turning in response to the cannabinoid infusions in the
      substantia nigra than unlesioned animals.

PMID- 9654337
TI  - Effects of neurotoxic doses of methamphetamine on potassium and amphetamine
      evoked overflow of dopamine in the striatum of awake rats.
AB  - The effects of neurotoxic doses of methamphetamine on basal and evoked overflow
      of dopamine in the striatum were examined in awake rats using microdialysis. Male
      Fischer-344 rats were administered methamphetamine (5 mg/kg s.c.) or saline four
      times in 1 day at 2-h intervals. Microdialysis experiments were carried out 1
      week later. Basal levels of dopamine, 3,4-dihydroxyphenylacetic acid, and
      homovanillic acid were reduced in the striatum of the methamphetamine-treated
      animals. Local application of excess potassium (100 mM) and amphetamine (100
      microM), and intraperitoneal injection of amphetamine (1.5 mg/ kg), led to
      increased levels of extracellular dopamine in the striatum of both
      methamphetamine- and saline-treated rats. However, the increase was significantly
      less in the methamphetamine-treated animals. Tissue levels of dopamine and
      metabolites were reduced in the striata of rats treated with methamphetamine.
      These results indicate that treatment with neurotoxic doses of methamphetamine
      can lead to functional changes in dopamine release in the striatum of Fischer-344
      rats.

PMID- 9654338
TI  - Anatomy of a new paired tract of the pineal gland in humans.
AB  - The human pineal gland and it anterior attachments were investigated grossly in
      the fresh state and microscopically in the sagittal plane and 25 degrees
      tangential to the coronal plane of sectioning. Fiber stains of tissue samples
      from the midline commissural attachments of the pineal gland indicated the
      presence of both myelinated and non-myelinated fibers connecting the pineal gland
      and the pre-tectal area. A previously unreported paired fiber tract was observed
      associated with the anterior inferio-ventro-lateral pineal gland. This paired
      tract appears to be physically separate and distinct from the posterior
      commissure. These tracts form a structural component of the wall of the pineal
      recess. The fibers coursing in this paired tract are myelinated, and are of two
      different sizes (1-3 microm diameter and 5-8 microm diameter) as determined by
      electron microscopy. Fibers from these tracts invade the pineal gland, and can be
      traced a short distance into the lateral pre-tectal area. The precise point of
      origin and termination for this paired tract is unknown.

PMID- 9654339
TI  - Intraseptal infusions of a low dose of AP5, a NMDA receptor antagonist, improves
      memory in an object recognition task in rats.
AB  - The present study describes the effects of intraseptal microinjections of 2 nmol
      of AP5 upon memory of rats subjected to a two trial object recognition task. This
      task allows us to detect either a disruption or an improvement of memory
      according to the duration of the interval between the sample trial (T1) and the
      choice trial (T2). AP5 injected before T1 did not disrupt memory in a schedule
      able to detect an amnesia. In a schedule able to detect an improvement of memory,
      AP5 injected either 10 min before or just after T1, or 10 min before T2, improved
      retention. These results suggest that microinjection of a low dose of AP5 in the
      septum improves the acquisition, the consolidation and the restitution of the
      information in a working memory task.

PMID- 9654340
TI  - Adenosine induces apoptosis by inhibiting mRNA and protein synthesis in chick
      embryonic sympathetic neurons.
AB  - Our previous work has established that adenosine is toxic to chick embryonic
      sympathetic neurons and kills freshly plated neurons by a process of apoptosis.
      Although the exact mechanism remains unknown, we found that phosphorylation of
      adenosine was essential to the toxicity. Using markers for RNA ([3H]uridine) and
      protein ([35S]methionine) synthesis we demonstrate here that in freshly plated
      sympathetic neurons adenosine inhibits RNA and protein synthesis by about 50%.
      The inhibitory effects of adenosine on RNA and protein synthesis, and increased
      ATP synthesis were blocked by adenosine kinase inhibitor, suggesting that
      phosphorylated products are responsible for inhibition of RNA and protein
      synthesis and cell death. Adenosine-induced inhibition of RNA and protein
      synthesis in neuronal cells provides a new role for adenosine in the regulation
      of cell function.

PMID- 9654341
TI  - GABAergic inhibition of neonatal rat phrenic motoneurons.
AB  - Phrenic motoneurons (PMNs) receive intermittently glutaminergic inspiratory
      drives and GABAergic inhibition in adult mammals. Since gamma-amino-butyric acid
      (GABA) might act as an excitatory amino acid in early stages of development, we
      here investigated if GABA(A) receptors inhibit PMNs in neonates. Using in vitro
      neonatal rat brainstem-spinal cord preparation, local application of GABA and
      muscimol (a GABA(A) receptor agonist) to the vicinity of PMNs consistently
      reduced the inspiratory activity of C4 ventral roots. Under whole-cell patch
      clamp conditions and in the presence of 0.5 microM TTX to block synaptic
      transmission, muscimol (10 microM) decreased whole-cell input resistance, and
      surprisingly, when PMNs were voltage-clamped at their resting membrane potential,
      muscimol induced depolarizing-inward, rather than hyperpolarizing-outward
      membrane current. Our findings indicate that GABA(A) receptors mediate a
      depolarizing blockade of the glutaminergic excitatory inputs to neonatal rat
      PMNs.

PMID- 9654342
TI  - Intracellular Ca2+ store-operated influx of Ca2+ through TRP-R, a rat homolog of
      TRP, expressed in Xenopus oocytes.
AB  - To elucidate whether rat transient receptor potential (TRP-R), a rat TRP4
      homolog, functions as a store-operated Ca2+ channel (SOC), we have measured the
      Ca2+ entry after thapsigargin treatment in Xenopus oocytes injected with mRNA for
      TRP-R. While non-injected oocytes elicited an SOC response, significantly larger
      responses were observed in the oocytes expressing TRP-R. The oocyte-native SOC
      response was inhibited by injection of antisense oligodeoxyribonucleotide for
      mammalian TRP1. When Ca2+ concentration-SOC response curve was examined, the EC50
      value was much smaller in oocytes expressing TRP-R than that of non-injected
      oocytes. These results suggest that TRP-R functions as SOC having higher
      sensitivity to external Ca2+ than amphibian TRP1 channel.

PMID- 9654343
TI  - NF-kappa B is activated and ICAM-1 gene expression is upregulated during
      reoxygenation of human brain endothelial cells.
AB  - Reperfusion injury is mediated, in part, by the upregulated expression of genes
      in microvascular endothelial cells that encode for inflammatory cytokines and
      adhesion molecules. The redox-regulated transcription factor, nuclear factor
      kappa B (NF-kappaB), may play a major role in the induced expression of these
      genes. In this study we use cultured human brain microvascular endothelial cells
      (HBMEC) to investigate whether reoxygenation of hypoxic HBMEC results in the
      activation of NF-kappaB and the upregulation of the adhesion molecule, ICAM-1.
      When HBMEC were subjected to hypoxia followed by reoxygenation but not hypoxia
      alone, an NF-kappaB complex composed of p65 and p50 Rel proteins was rapidly
      activated within 15-30 min. Four hours later, expression of the ICAM-1 gene was
      significantly upregulated. The antioxidant pyrrolidine dithiocarbamate and the
      proteasome inhibitor, n-Tosyl-Phe-chloromethyl ketone, blocked both the
      activation of NF-kappaB and the upregulation of the ICAM-1 gene. These results
      indicate that NF-kappaB is activated in HBMEC by reoxygenation and may play a
      significant role in the upregulation of the ICAM-1 gene. Agents which inhibit NF
      kappaB activation may be potential therapeutic agents in acute ischemic stroke.

PMID- 9654344
TI  - Entrainment of the medullary respiratory generators by electrical stimulation in
      the cervical grey matter on in vitro preparations of newborn rat.
AB  - The present study describes how the medullary respiratory generators (mRGs) can
      be driven by periodic electrical stimulations applied to the ventral part of the
      spinal grey matter at the C5 level. The general effect of an electrical stimulus
      (5 pulses at 200 Hz and between 50 and 80 microA) was either to delay or to
      advance the occurrence of the medullary respiratory burst via a resetting
      process, depending on its time of application within the corresponding cycle.
      Compared to the spontaneous medullary periods, the phase-response curves show
      that the non-spontaneous medullary period increased progressively when the
      electrical stimulus was applied within the first two-thirds of the corresponding
      medullary cycle and decreased when it was applied within the last third of the
      latter one. These curves were constructed in order to predict the limits of a
      stable 1:1 entrainment. As predicted, the 1:1 entrainment was obtained when we
      stimulated repetitively at resetting intensity within the frequency limits
      determined by the phase-response curves. The entrainment became harmonic (2:1,
      3:1, 4:1) when the stimulation frequency increased near submultiples of the
      fundamental mRGs frequency. From these data, we conclude on the presence of
      ascending connections from the C5 segment of the spinal cord which might be
      involved in the realisation of the locomotor-respiratory coupling.

PMID- 9654345
TI  - Kindling-induced neurogenesis in the dentate gyrus of the rat.
AB  - Kindling, a form of neuronal plasticity produced by repeated low intensity
      electrical brain stimulation, leads to epileptic seizures. To address possible
      causes of this phenomenon, we have prepared amygdala-kindled animals and measured
      neurogenesis, by bromodeoxyuridine incorporation. Early, when focal seizures were
      present, there was no evidence of a change in the rate of hippocampal
      neurogenesis. In contrast, during the later phases of kindling, when secondary
      generalization was well established and motor seizures were present, neurogenesis
      was enhanced by 75-140%, depending on the hippocampal region. Double labelling
      with the neuron-specific marker TOAD-64 demonstrated the presence of numerous new
      born granule neurons in the kindled animals. We propose that the newly-born
      neurons contribute to the cellular changes and behavioral symptoms associated
      with this type of epileptiform brain plasticity.

PMID- 9654346
TI  - Lysophosphatidylserine potentiates nerve growth factor-induced differentiation of
      PC12 cells.
AB  - Since lysophosphatidylserine (LPS) is required for nerve growth factor (NGF)
      induced secretion of histamine from rat mast cells, we investigated whether LPS
      might potentiate the effects of NGF in inducing neural differentiation of PC12
      cells. Cell morphology was evaluated 48 h after addition of NGF, LPS or NGF +
      LPS. LPS alone was ineffective, but strongly promoted NGF-induced differentiation
      to give rise to cells that more closely resembled neurons in primary culture. LPS
      increased the number of PC12 cells that developed neurites in response to NGF
      (0.01-40 ng/ml), with the response to 1.0 ng/ml increasing from 17.8 +/- 2.2 to
      50.8 +/- 4.1% when LPS was also present. Neurite length was also greater in PC12
      cells receiving NGF + LPS: 17.8 +/- 2.2% of cells had neurites longer than three
      cell body diameters with 1.0 ng/ml NGF + 1 microg/ml LPS, compared to 1.6 +/-
      1.6% with NGF alone. Further, cells responding to NGF + LPS typically developed
      only 1-2 neurites per cell (90.9%, 1 microg/ml LPS), compared with the multipolar
      appearance with NGF alone (71.1% with 3-6 neurites, 10 ng/ml NGF). LPS occurs at
      sites of tissue damage where NGF can also be present, and therefore may be a
      naturally-occurring modifier of neuronal structure and/or function.

PMID- 9654348
TI  - Expression of beta-endorphin and its receptors in the spinal cord of obese
      diabetic ob/ob mice.
AB  - Immunocytochemistry was used to demonstrate the presence of beta-endorphin, and
      quantitative autoradiography with [125I]beta-endorphin was used to study beta
      endorphin binding sites, in spinal cord of lean and obese diabetic ob/ob mice.
      The proportion of beta-endorphin-positive neurones was approximately 6-fold
      higher in the ventral horn, and 2-fold higher in the dorsal horn of ob/ob mice
      than in lean controls. The maximum density of beta-endorphin binding sites was
      significantly higher in the dorsal horn and intermediate zone of ob/ob mice. The
      Kd value for the binding was similar in the ventral horn and intermediate zone in
      lean and ob/ob mice, but slightly lower in the dorsal horn of ob/ob mice. The
      findings indicate upregulation of both beta-endorphin and its receptors in spinal
      neurones of ob/ob mice.

PMID- 9654347
TI  - Concurrent decrease of vasopressin and protein kinase Calpha immunoreactivity
      during the light phase in the vole suprachiasmatic nucleus.
AB  - Vasopressin (AVP) is a major neuropeptide in the suprachiasmatic nucleus, the
      mammalian hypothalamic circadian pacemaker. Protein kinase Calpha is a putatively
      coupled intracellular messenger. Mean numbers of AVP- and protein kinase Calpha
      immunoreactive neurons were determined in the suprachiasmatic nucleus of common
      voles, entrained to a 12:12 h light-dark (LD) cycle, at the beginning of the
      light period (zeitgeber time zero) and 6 h later (zeitgeber time six). At
      zeitgeber time zero, mean numbers of AVP- and protein kinase Calpha-
      immunoreactive neurons were 2194 and 9897, respectively. Both numbers decreased
      significantly with about 40% at zeitgeber time six. This concurrent decrease was
      most pronounced in the dorsomedial aspect of the suprachiasmatic nucleus. These
      findings are consistent with the findings of a peak of AVP release in rats during
      the early light phase.

PMID- 9654349
TI  - Peripheral fields of sympathetic vasoconstrictor neurons in guinea pigs.
AB  - We have combined retrograde axonal tracing using Fast Blue and Dil, with
      immunohistochemistry, to estimate the maximum size of peripheral fields of
      identified sympathetic vasoconstrictor neurons projecting to guinea-pig ear tips.
      Many neurons in the superior cervical ganglia were labelled with both Fast Blue
      and Dil after dye injections up to 7 mm apart. Few neurons were labelled when dye
      injections were 8-10 mm apart. Neurons labelled with both Dil and Fast Blue after
      dye injections 5-7 mm apart had, on average, larger somata (436 +/- 84 microm2,
      mean +/- SEM, n = 47) than neurons labelled with Dil only (388 +/- 11 microm2, n
      = 147). Typically, 50-100 neurons innervated a region of vasculature 1 mm in
      diameter. We conclude that sympathetic vasoconstrictor neurons branch widely
      before converging on to their target blood vessels. Progressive recruitment of
      vasoconstrictor neurons with increasing field size would provide an efficient
      mechanism for graded neural control of the circulation.

PMID- 9654350
TI  - Noradrenaline neurotoxin DSP-4 effects on sleep and brain temperature in the rat.
AB  - N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) has a selective degenerative
      effect on noradrenergic fibers originating from locus coeruleus (LC) neurons. In
      the present study, we studied its effect on vigilance states and brain
      temperature by continuous recordings for periods of 1-5 days and 2-4 weeks
      following DSP-4 treatment. On the first day, paradoxical sleep duration was
      significantly decreased (-67%, P < 0.05), slow-wave sleep (SWS) duration
      increased (+16%, P < 0.05) up to 48 h after DSP-4 treatment (+8%, P < 0.05) and
      the wake period decreased (-8%, P < 0.05). The vigilance states returned to
      control values 4-5 days later. The brain temperature was decreased during the
      first night (-2 degrees C) and then recovered the control values. Two and 4 weeks
      after DSP-4 treatment, paradoxical sleep was still decreased (-18% and -23%,
      respectively, P < 0.05), while SWS was significantly increased only at night
      during the fourth week (+23%, P < 0.05). These results therefore provide evidence
      for a differential involvement of the noradrenergic LC system in sleep mechanisms
      depending on the light-dark cycle. Different hypotheses are proposed.

PMID- 9654351
TI  - Development of systemic lupus erythematosus in mice is associated with alteration
      of neuropeptide concentrations in inflamed kidneys and immunoregulatory organs.
AB  - In the present study we used a well-characterised model of murine lupus, the
      female NZB/W hybrid, to study the possible involvement of neuropeptides in the
      pathogenesis of systemic lupus erythematosus (SLE). Analysis of neuropeptides
      with a possible role in inflammation showed that substance P (SP) calcitonin gene
      related peptide (CGRP) and neuropeptide Y (NPY) are present in increased
      quantities in the inflamed kidneys of SLE mice, confirming their involvement in
      local inflammation, while there is a general reduction in the peptide
      concentrations in the lymphoid organs of lupus mice, except for NPY. Our results
      suggest that the altered neuropeptide concentrations observed in the SLE lymphoid
      organs may be partly responsible for the altered immune response and contribute
      to the development of autoimmune diseases.

PMID- 9654352
TI  - Cysteine dioxygenase: regional expression of activity in rat brain.
AB  - The levels of expression of cysteine dioxygenase (CDO) protein and activity were
      investigated in nine functionally distinct regions of the rat brain before and
      after induction with methionine by Western analysis and an activity assay.
      Activity expression ranged from no activity in the brain-stem to high activity
      expression in the olfactory bulb and basal ganglia. Upon exposure to 400 mg/l
      methionine for 5 days, significant induction of expression was observed in the
      basal ganglia, brain-stem, cerebellum, hippocampus, midbrain and olfactory bulb.
      Protein expression appeared to correlate with activity expression when levels
      before and after induction were compared. This non-uniformity of expression may
      reflect different physiological functions of CDO in these areas.

PMID- 9654353
TI  - Formation and sequence analysis of secretoneurin, a neuropeptide derived from
      secretogranin II, in mammalian, bird, reptile, amphibian and fish brains.
AB  - Secretoneurin is a recently-characterized neuropeptide derived from secretogranin
      II, a protein belonging to the class of chromogranins. We investigated the
      phylogeny of this peptide by immunoblotting and gel-filtration high performance
      liquid chromatography followed by radioimmunoassay of brain extracts of various
      species including chicken, lizard, frog and fish. In addition the amino acid
      sequence of secretoneurin from pig, hamster, rabbit, guinea-pig and chicken was
      established by reverse transcriptase polymerase chain reaction. Secretoneurin is
      strongly conserved during evolution, it is not only expressed in various
      mammalian species but found also in the brain of birds, reptiles, amphibians and
      fish. In all these species a significant or near complete processing of
      secretogranin II to secretoneurin was observed. These data provide significant
      evidence for the neuropeptide nature of the novel functional peptide.

PMID- 9654354
TI  - m-Calpain (calcium-activated neutral proteinase) in Alzheimer's disease brains.
AB  - An antibody specific for the calpain isoform m-calpain was used to resolve
      conflicting results from several studies on the possible role of m-calpain in the
      pathogenesis of Alzheimer's disease (AD). Levels of the enzyme in both cytosolic
      and membranous fractions of brain tissue were determined by Western blot
      analysis. We also demonstrated changes in m-calpain molecules in AD brains using
      high-resolution 2D gel electrophoresis (2DE). The levels of the m-calpain isoform
      detected in the cytosolic fraction were significantly increased in AD brains when
      compared with the levels in controls. On 2DE, m-calpain molecules resolved into
      eight main spots. These spots were detected in AD brains as well as in control
      brains, suggesting that the calpain molecule was not qualitatively changed in AD.
      Quantitative analysis of the m-calpain spots on 2DE, on the other hand, indicated
      that the ratio of the intensity of four protein spots in the acidic region to
      that of the total spots was increased in AD brains.

PMID- 9654355
TI  - Dependence of sympathetic vasomotor tone on bilateral inputs from the rostral
      ventrolateral medulla in the rabbit: role of baroreceptor reflexes.
AB  - A unilateral microinjection of muscimol into the pressor region in the rostral
      ventrolateral medulla (RVLM) of anaesthetised baroreceptor-denervated rabbits
      resulted in large and sustained decreases in mean arterial pressure, renal
      sympathetic nerve activity and heart rate (maximal decreases of 41 +/- 4 mmHg, 64
      +/- 3%, and 59 +/- 8 beats/min, respectively). Subsequently, muscimol
      microinjection into the contralateral RVLM pressor region resulted in further but
      much smaller decreases in these variables. In contrast, it is well established
      that in baro-intact animals unilateral inactivation of the RVLM pressor region
      has little effect on resting sympathetic activity or arterial pressure -
      bilateral inactivation is required to produce large and sustained decreases. The
      results of the present study indicate that the baroreceptor reflex plays a
      crucial role in maintaining resting sympathetic vasomotor activity under
      circumstances in which the activity of RVLM presympathetic neurons is partially
      impaired.

PMID- 9654356
TI  - Prepulse facilitation of auditory startle response in hamsters.
AB  - A visual prepulse was applied just before a burst of white noise with various
      lead intervals ranging from 50 to 400 ms in hamsters. After habituation each
      hamster received 120 trials of the auditory noise with or without the prepulse.
      Amplitude of startle response increased significantly at 100 ms and 200 ms (n =
      10). This enhancement disappeared in blind controls (n = 6). The amplitude of
      startle response decreased during exploratory behavior, grooming, sniffing or
      other movements. However, the facilitatory effects of the visual prepulse were
      consistent, regardless of the animal's behavioral states, except sniffing. The
      authors conclude that visual prepulse task is useful for studying the ability to
      detect visual signals in hamsters, and that further study is necessary to
      elucidate the factors affecting the enhancement of startle response in hamsters.

PMID- 9654357
TI  - Biphasic effect of aluminium on cholinergic enzyme of rat brain.
AB  - The cholinotoxic effect of aluminium has been widely reported. In vitro aluminium
      has a biphasic effect on acetylcholinesterase activity. The present study
      analyses its in vivo effect in brain regions. Rats were exposed to aluminium
      chloride by the oral route at a dose of 320 mg/kg body weight for shorter (4 and
      14 days) and longer (60 days) duration. Acetylcholinesterase activity in
      olfactory bulb, striatum and hypothalamus brain regions increased after 4 and 14
      days and decreased after 60 days of aluminium exposure. Aluminium level in the
      brain regions studied increased significantly. No significant change in body
      weight of rats exposed to aluminium was found. The biphasic change in
      acetylcholinesterase activity may be due to slow accumulation of aluminium in the
      brain regions and its effect on the enzyme.

PMID- 9654358
TI  - Sevoflurane suppresses behavioral response in the rat formalin test: combination
      with intrathecal lidocaine produced profound suppression of the response.
AB  - We investigated the effects of intrathecal (i.t.) lidocaine, inhalation
      sevoflurane, and a combination of i.t. lidocaine and sevoflurane on the formalin
      test in rats. Group 1 (control) received i.t. saline 10 microl. Groups 2 and 3
      received i.t. lidocaine 200 microg and 400 microg, respectively. Groups 4-6
      received 1.2%, 2.4% and 3.6% sevoflurane, respectively. Interaction of drugs was
      analyzed using a dose addition model. Group 7 received i.t. lidocaine 200 microg
      and 1.2% sevoflurane. The biphasic behavioral activity of the hindpaw of rats was
      observed. This study showed that i.t. lidocaine or inhalation sevoflurane before
      formalin injection, significantly suppressed the behavioral activity of the
      hindpaw of rats, and that this suppression was significantly potentiated by the
      co-administration of i.t. lidocaine and inhalation sevoflurane.

PMID- 9654359
TI  - Nitric oxide activates Ca2+-activated K+ channels in cultured bovine adrenal
      chromaffin cells.
AB  - The effects of sodium nitroprusside (SNP) on Ca2+-dependent K+ (KCa) channels in
      cultured bovine adrenal chromaffin cells were investigated using single channel
      recording patch-clamp techniques. KCa channels were activated by application of
      100 microM SNP to the extracellular side of cell-attached patches. Methylene blue
      (300 microM), an inhibitor of soluble guanylate cyclase, or H-8 (1 microM), a
      protein kinase inhibitor with relative specificity for cGMP-dependent protein
      kinase, diminished but did not completely abolish the SNP-induced KCa channel
      activation. Diethylamine/NO complex (DEA/NO), an NO donor, also activated KCa
      channels in cell-attached patches. Furthermore, application of 100 microM SNP or
      100 nM DEA/NO to the intracellular surface of excised inside-out patches also
      activated KCa channels in the bath solution which contained 1 microM Ca2+. These
      results indicate that SNP is capable of activating the KCa channel via cGMP
      dependent and -independent mechanisms. These studies demonstrate that NO may
      serve as an important regulatory mechanism for catecholamine secretion in
      chromaffin cells via the activation of KCa channels.

PMID- 9654360
TI  - ATP produces potassium currents via P3 purinoceptor in the follicle cell layer of
      Xenopus oocytes.
AB  - Purinoceptor agonists produced potassium currents with the order of potency: ATP
      > adenosine = ADP = AMP > beta,gamma-methylene ATP, while a small response or no
      response was induced by 2-methylthio ATP, UTP, or alpha,beta-methylene ATP. The
      response induced by beta,gamma-methylene ATP was completely inhibited in the
      presence of alpha,beta-methylene ATP, suggesting that the relevant receptor for
      these agonists was a P3 purinoceptor. ATP induced currents with a latency of 24 s
      and the currents were not induced in defolliculated oocytes. The currents were
      not affected by either the Gi/o-protein inhibitor, pertussis toxin (PTX), or the
      selective cAMP-dependent protein kinase inhibitor, H-89, or the phospholipase C
      (PLC) inhibitor, neomycin, or the phospholipase A2 (PLA2) inhibitor, 4
      bromophenacyl bromide. The currents were enhanced by the selective protein kinase
      C (PKC) inhibitor, GF109203X, but otherwise, they were reduced by the potent PKC
      activator, 12-O-tetradecanoylphorbol-13-acetate. The results of the present study
      suggest that a P3 purinoceptor in the follicle cell layer of oocytes is involved
      in activation of potassium channels and that the evoked currents are regulated by
      PLC/PLA2-independent PKC activation.

PMID- 9654361
TI  - Polyethylene glycol-induced hypovolemia affects the expression of MCH mRNA, but
      not dynorphin or secretogranin II mRNAs, in the rat lateral hypothalamus.
AB  - Two prominent neuron populations of the rat lateral hypothalamus express genes
      encoding respectively the prepromelanin-concentrating hormone (MCH) or dynorphin
      (DYN) and secretogranin II (SGII). Their roles remain hypothetical in mammals. In
      the present study, we examined the changes in MCH, DYN and SGII gene expression
      in dehydrated rats compared to controls. Dehydration was obtained by subcutaneous
      injection of polyethylene glycol (PEG) resulting in a large reduction of the
      extracellular fluid volume. Using competitive semi-quantitative RT-PCR and in
      situ hybridization methods, PEG-injected animals showed a significant increase of
      MCH mRNA level but no variation of DYN and SGII mRNA levels. These results
      confirm previous observations suggesting that intra- and extracellular
      dehydration challenges affect different regulation circuits; they indicate that
      both neuron populations could be involved in the maintenance of body fluid
      homeostasis, directly, or indirectly, as integrators of various information
      leading to goal-oriented behaviour.

PMID- 9654362
TI  - GABA(b) receptors differentially regulate hippocampal CA1 excitatory synaptic
      transmission across postnatal development in the rat.
AB  - Depression of excitatory postsynaptic potentials (EPSPs) by the GABA(b) agonist,
      baclofen, was compared in hippocampal slices from juvenile (postnatal day (P) 15
      21) and young adult (P28-35) rats. EPSP inhibition following baclofen application
      was not different between age groups, however, paired-pulse facilitation (PPF)
      increased more in young adults relative to juveniles. The differential effect of
      baclofen on PPF was not due to tonic receptor activity, since the GABA(b)
      antagonist, saclofen, did not differentially modify PPF. The baclofen-mediated
      increase in PPF for juvenile slices could be enhanced by first increasing
      transmitter release through an increased bath Ca2+ concentration. These findings
      suggests that ligand-mediated presynaptic depression is inversely related to the
      level of transmitter release and maturation of presynaptic inhibition is related
      to development of release.

PMID- 9654363
TI  - Regulation of the phosphorylation of glial fibrillary acidic protein (GFAP) by
      glutamate and calcium ions in slices of immature rat spinal cord: comparison with
      immature hippocampus.
AB  - The effect of glutamate and lack of external Ca2+ on the phosphorylation of the
      astrocyte cell marker glial fibrillary acidic protein (GFAP) was studied in
      slices of hippocampus and thoracic spinal cord from immature (P12-16) rats.
      Confirming previous work with immature hippocampal slices (Wofchuk, S.T. and
      Rodnight, R., Neurochem. Int., 24 (1994) 517-523; Wofchuk, S.T. and Rodnight, R.,
      Dev. Brain Res., 85 (1995) 181-186), glutamate strongly stimulated GFAP
      phosphorylation in media with Ca2+ and in media lacking Ca2+ a quantitatively
      similar stimulation of basal GFAP phosphorylation was observed. By contrast in
      slices of immature thoracic spinal cord, glutamate had no effect on GFAP
      phosphorylation and in media lacking Ca2+ phosphorylation of GFAP was inhibited.
      Since GFAP phosphorylation is Ca2+-dependent and is not stimulated by glutamate
      in slices of adult hippocampus, the present results suggest that astrocytic
      functions in the rat spinal cord mature more rapidly than in the hippocampus. The
      possibility that the difference in the control of GFAP phosphorylation in the two
      structures is related to differences in the control of GFAP dephosphorylation was
      investigated by incubating spinal cord slices with the calcineurin inhibitor
      FK506 in the presence of Ca2+. In contrast to results obtained with hippocampal
      slices FK506 had no effect on the phosphorylation state of GFAP in spinal cord
      slices.

PMID- 9654364
TI  - Central administration of urocortin inhibits vasopressin release in conscious
      rats.
AB  - Urocortin (UCN) is a new mammalian member of the corticotropin releasing factor
      (CRF) family and supposed to be an endogenous ligand for type 2 CRF receptors.
      Previous studies have revealed that UCN mRNA exists in the supraoptic nucleus
      (SON), and that water deprivation increases UCN immunoreactivity in SON. In this
      study, we examined the effect of centrally-administered UCN on arginine
      vasopressin (AVP) release in conscious rats. Intracerebroventricular (i.c.v.)
      injection of UCN (5.0 microg/rat) significantly attenuated AVP release induced by
      hyperosmolality at 30 min after the injection. In contrast, CRF (5.0 microg/rat)
      injected i.c.v. had no significant effect on AVP release. These results suggest
      that central UCN play an inhibitory role in osmoregulation of AVP release.

PMID- 9654365
TI  - Epitope specificity of a monoclonal antibody generated against the dissociated
      CFA/I fimbriae of enterotoxigenic Escherichia coli.
AB  - A monoclonal antibody (MAb 84) raised against the dissociated CFA/I fimbriae of
      enterotoxigenic Escherichia coli was characterized with regard to antigen binding
      and epitope specificity. Enzyme-linked immunosorbent assay (ELISA) showed that
      MAb 84 had higher affinity to CFA/I subunits than to intact CFA/I fimbriae and
      recognized a Salmonella flagellin carrying an insert corresponding to amino acids
      32 to 45 of the CFA/I subunit. Fine epitope mapping based on the Pepscan
      technique showed that the peptide 39TFESY43, derived from the sequence of the
      mature CFA/I subunit, was specifically recognized by MAb 84. The 39TFESY43
      sequence is probably not accessible on the surface of the native CFA/I fimbriae
      since MAb 84 did not bind to intact fimbriae as evaluated in inhibition ELISA
      tests. Moreover, MAb 84 did not agglutinate fimbriated ETEC cells nor inhibit
      CFA/I-mediated hemagglutination or the adhesion to Caco-2 cells.

PMID- 9654366
TI  - Culture supernatants of Lactobacillus acidophilus and Bifidobacterium
      adolescentis repress ileal ulcer formation in rats treated with a nonsteroidal
      antiinflammatory drug by suppressing unbalanced growth of aerobic bacteria and
      lipid peroxidation.
AB  - A nonsteroidal antiinflammatory drug, 5-bromo-2-(4-fluorophenyl)-3-(4
      methylsulfonylphenyl) thiophene (BFMeT), induced ileal ulcers in rats after oral
      administration, while no ulcers were observed after subcutaneous injection. The
      ileal ulcer formation in BFMeT-treated rats was examined to correlate the
      administration of cultures of Lactobacillus acidophilus or Bifidobacterium
      adolescentis with intestinal bacteria in the ileal contents and lipid
      peroxidation of the small intestinal mucosa. Ileal ulcers were observed in more
      than 85% of the rats treated with BFMeT at a dose of 1,000 mg/kg when they were
      given tap water as drinking water. The incidence of ulcer formation was repressed
      by giving culture supernatants of L. acidophilus or B. adolescentis as drinking
      water, but not by giving the cell suspension as drinking water. Gram staining of
      the ileal contents of normal rats revealed that 97% of the stained bacteria were
      gram-positive rods and only 1.5% were gram-negative rods. The percentage of gram
      negative rods 72 hr after BFMeT administration was 49.8% and increased over 30
      fold in BFMeT-treated rats. However, the percentage of gram-negative rods was 9.7
      % or 16%, respectively, in rats taking culture supernatants of L acidophilus or
      B. adolescentis. In addition, thiobarbituric acid-reactive substances in the
      ileal mucosa increased significantly in the rats given tap water for 72 hr after
      BFMeT treatment, but not in rats given the culture supernatants of L. acidophilus
      or B. adolescentis. Since BFMeT induced an unbalanced intestinal microflora, the
      effect of antibiotic treatment on ulcer formation in rats was examined. The
      magnitude of the ulcer formation in the antibiotic-treated rats was, in
      decreasing order, metronidazole >none > kanamycin > a mixture (bacitracin,
      neomycin and streptomycin). These results suggest that the intestinal microflora
      plays an important role in ulcer formation and that a metabolite(s) of L.
      acidophilus and B. adolescentis inhibits ileal ulcer formation by repressing
      changes in the intestinal microflora and lipid peroxidation in BFMeT-treated
      rats.

PMID- 9654367
TI  - Cellular reaction to Mycobacterium avium complex (MAC) clinical isolates
      differing in hemolytic activity and virulence for C57BL/6 mice.
AB  - In this study we showed that Mycobacterium avium complex (MAC) clinical isolates
      differed by the expression of hemolytic activity. Two hemolytic MAC strains were
      less susceptible to the mycobactericidal effect of murine macrophages than two
      unhemolytic MAC isolates. In vivo, hemolytic MAC bacilli survived in the spleens
      of infected mice for a longer time than unhemolytic MAC strains. This suggested a
      role of hemolysins in the virulence of MAC strains. There was no difference in
      the cytotoxicity of T cells from mice immunized with M. bovis BCG towards
      macrophages infected in vitro with MAC strains expressing or not expressing
      hemolytic activity.

PMID- 9654368
TI  - Morphological alterations of Saccharomyces cerevisiae induced by benanomicin A,
      an antifungal antibiotic with mannan affinity.
AB  - The effects of benanomicin A, a mannose-binding antifungal antibiotic, on yeast
      cells of Saccharomyces cerevisiae were studied by electron microscopy.
      Cytological studies using vital stain with methylene blue demonstrated that
      benanomicin A at 20 and 80 microg/ml killed buds in preference to parent cells.
      In confirmation, examination by TEM revealed that benanomicin A at 80 microg/ml
      damaged buds more severely than parent cells. The major effect on the
      ultrastructure was characterized by severe damage to the cell membrane. In
      addition, it caused expansion and vacuolation of the endoplasmic reticulum (ER),
      and partial fragmentation and disappearance of nuclear membranes. The membrane
      disruptive activity of benanomicin A may be closely associated with its membrane
      affinity.

PMID- 9654369
TI  - Detection of verotoxin-producing Escherichia coli O157:H7 by multiplex polymerase
      chain reaction.
AB  - We constructed primers for multiplex polymerase chain reaction (PCR) to detect
      verotoxin-producing Escherichia coli (VTEC) O157:H7. The multiplex PCR primers
      were designed from the sequence of the flagellin structural gene of Escherichia
      coli flagellar type H7 (GenBank under accession number L07388), and from the
      sequence of the rfbE gene of Escherichia coli O157:H7 (GenBank under accession
      number S83460). In addition to these primers, we used a primer pair reported by
      Karch and Meyer (J. Clin. Microbiol. 27: 2751-2757, 1989) to amplify various VT
      genes from VTEC. All of the examined specimens (18 isolates) of VT-producing E.
      coli O157:H7 showed a positive result by the multiplex PCR test with the three
      sets of primers. The sensitivity of detection for VT-producing E. coli O157:H7
      was shown to be at least 3,000 cells per PCR tube.

PMID- 9654370
TI  - Requirement of cauliflower mosaic virus open reading frame VI product for viral
      gene expression and multiplication in turnip protoplasts.
AB  - Cauliflower mosaic virus (CaMV) open reading frame (ORF) VI product (P6) has been
      shown to be the major constituent of viral inclusion body, to function as a post
      transcriptional transactivator, and to be essential for infectivity on whole
      plants. Although these findings suggest that P6 has an important role in viral
      multiplication, it is unknown whether P6 is required for viral multiplication in
      a single cell. To address this question, we transfected turnip protoplasts with
      an ORF VI frame-shift (4 bp deletion) mutant (pCaFS6) of an infectious CaMV DNA
      clone (pCa122). The mutant was uninfectious. Co-transfection of plasmids
      expressing P6 complemented the mutant. Overexpression of P6 elevated the
      infection rate in co-transfection experiments with either pCa122 or pCaFS6. This
      would have been achieved by elevating the level of pregenomic 35S RNA, a putative
      polycistronic mRNA for ORFs I, II, III, IV and V, and by enhancing the
      accumulation of these five viral gene products. When CaMV ORFs I, II, III, IV and
      V were expressed from monocistronic constructs in which each of the ORFs was
      placed just downstream of the 35S promoter, the accumulation of ORF III, IV and V
      products depended on the co-expression of P6. The accumulation of ORF I and II
      products was not detected, even in the presence of P6. These results suggest that
      P6 is involved in the stabilization of other viral gene products as well as in
      the activation of viral gene expression, and thus, is a prerequisite for CaMV
      multiplication.

PMID- 9654371
TI  - Serological differentiation between HCV subtypes 1a and 1b by a recombinant
      immunoblot assay.
AB  - Until now, no serological assay has been available for the differentiation of HCV
      subtypes. Since there is evidence that the subtypes differently influence the
      clinical course of HCV infection and the outcome of interferon therapy, we
      established a strip immunoblot assay (NS-4 IBA) with recombinant HCV proteins of
      the nonstructural 4 (NS-4) region propagated in Escherichia coli. Using this NS-4
      IBA, we were able to distinguish HCV subtypes 1a and 1b, which are the most
      prevalent subtypes in Europe and the U.S.A. The results of the serotyping assay
      were compared with those obtained by nucleotide sequencing from the NS-5 region.
      Concordant results were observed to match 94.9% (n=100) by the NS-4 IBA and
      nucleotide sequencing. Discrepant results were obtained in only 5.1% (n=6). These
      data indicate that HCV subtypes can be serologically distinguished, providing the
      possibility for easier identification of infection with different HCV subtypes.

PMID- 9654372
TI  - Measurement of arginine carboxypeptidase-generating activity of adult plasma.
AB  - Arginine carboxypeptidase (CPR) is a novel carboxypeptidase which was first
      described by Campbell and Okada. CPR is generated from a stable precursor of CPR
      (proCPR) during coagulation or under other circumstances and is promptly
      inactivated at 37 C. Therefore, it is not easy to determine CPR in blood samples.
      Since proCPR can be separated from the other basic carboxypeptidase
      (carboxypeptidase N; CPN) by passing plasma through DEAE gel, we have established
      a method to determine the amount of proCPR after converting it to active CPR by
      trypsin treatment. We first separated the proCPR from CPN using a filter cup tube
      (FC tube) packed with DEAE Sephadex, and measured activity after conversion of
      the enzyme to its active form using trypsin. With this method, no significant
      decrease in proCPR was noted in the plasma of patients including those with
      rheumatoid arthritis (RA), although CPR activity in fresh sera has been reported
      to be decreased. This discrepancy suggests that proCPR is not depleted in most
      patient sera, but that the level of activity of the enzyme which converts proCPR
      into active CPR may be compromised in RA patients.

PMID- 9654373
TI  - Regulation of promoter and intron enhancer activity in immunoglobulin heavy-chain
      genes during B-cell differentiation.
AB  - Chloramphenicol acetyltransferase (CAT) transgenic mice, in which the transgene
      is regulated by the VH promoter and heavy-chain intron enhancer (E mu), were
      examined to investigate the variation of activity of these cis-acting elements
      during the late stage of B-cell development. CAT enzyme activity decreased when
      resting B cells were stimulated through B-cell receptors (BCR) with goat anti
      mouse IgM antibodies in vitro. On the other hand, when these B cells were
      stimulated by lipopolysaccharide (LPS) in vitro, they showed enhanced CAT
      activity, accompanied by an increase in the number of CD43+ B220+ cells (pro
      plasma and plasma cells). In addition, the CAT activities in CD43+ B220+ and
      PNAhi B220+ cells from immunized mice were higher than those in CD43- B220+ and
      PNAlo B220+ cells, respectively. These results suggest that the activity of E mu
      in the context of VH promoter was transiently down-regulated by stimulation
      through the BCR but enhanced at the pro-plasma and plasma stages.

PMID- 9654374
TI  - Occurrence of coagulase serotype among Staphylococcus aureus strains isolated
      from healthy individuals--special reference to correlation with size of protein-A
      gene--.
AB  - One-hundred-and-nineteen strains of Staphylococcus aureus isolated from healthy
      individuals for 3 years between 1991 and 1993 were subjected to an investigation
      on the producibility of proteins including protein A, coagulase, enterotoxins and
      toxic-shock syndrome toxin-1. Especially, protein A was the center of our
      interest. Among these strains, 69, 43, 3 and 1 strains were found to have the
      protein-A gene containing 5, 4, 3 and 2 IgG-binding domains, respectively. On the
      other hand, only one strain was devoid of the protein-A gene. There were some
      differences in the profile of the coagulase serotype between the group with 4 IgG
      binding domains and that with 5 IgG-binding domains. Differences in the profile
      of toxin production were also observed between the two groups.

PMID- 9654375
TI  - Differentiation of Chlamydia species by combined use of polymerase chain reaction
      and restriction endonuclease analysis.
AB  - To differentiate Chlamydia spp., a primer pair designed to generate a genus
      specific region of the major outer membrane protein (MOMP) gene was used in a PCR
      to amplify a single DNA fragment of 245-259 bp. In the PCR, the expected single
      DNA fragment was amplified from strains of Chlamydia trachomatis, C. psittaci, C.
      pneumoniae and C. pecorum, respectively. By restriction endonuclease analysis
      with AluI and PvuII, the amplified products exhibited four distinct patterns,
      corresponding to the four species. It is, therefore, concluded that one-step PCR
      followed by restriction endonuclease analysis as described in this study could be
      a valuable method for the detection and differentiation of Chlamydia species.

PMID- 9654376
TI  - Seeking order in disorder: computational studies of neurologic and psychiatric
      diseases.

PMID- 9654377
TI  - Methodology and validity in the construction of computational models of cognitive
      deficits following brain damage.
AB  - Over recent years, neural network models of several cognitive neuropsychological
      disorders have been developed. These include word recognition difficulties, face
      recognition difficulties, attentional deficits, visual processing impairments,
      semantic deficits, and aphasia. These models are useful in various ways. Firstly,
      they require detailed specifications of theories, and can focus attention on
      critical assumptions. Secondly, they can query alternative theories, and provide
      predictions which can be verified by testing patients. In this paper, issues
      relating both to the methodology and validity of attempts to model cognitive
      deficits using neural networks will be discussed, providing examples from several
      studies. Issues discussed will include the requirement for models to perform
      normally prior to damage, and to show potential effects of rehabilitation or
      partial recovery following damage. A single model should be able to incorporate
      multiple symptoms of a deficit and ideally also multiple syndromes when different
      lesions are introduced. The model must also be able to handle variability between
      patients with the same syndrome, and even with the same patient at different test
      sessions.

PMID- 9654378
TI  - Striatal mechanisms in Parkinson's disease: new insights from computer modeling.
AB  - We review data and hypotheses concerning the functional anatomy of the striatum
      and the role of its corticostriatal and nigrostriatal afferents in Parkinson's
      disease (PD). Starting from molecular mechanisms of glutamatergic and
      dopaminergic actions in the striatum we have developed a compartmental model of
      striatal principal neurons that displays a significant degree of biological
      realism. Simulations of a network of striatal projection neurons under conditions
      likely to be found in healthy subjects as well as untreated and therapeutic
      situations of advanced PD provide clues concerning the dynamics of neuronal
      interactions and their possible effects on downstream motor structures in the
      generation of positive and negative motor symptoms. We present tentative
      biological explanations of the symptoms of rigidity and akinesia in PD leading to
      predictions concerning the origin of abnormal movements and the beneficial
      effects of dopaminergic treatment. Although these attempts are not yet sufficient
      to account for the complexity of clinical symptoms found in PD they can guide
      further empirical research and foster fruitful interactions between
      experimentalists, theoreticians, and clinicians in unraveling the functional
      anatomy of the basal ganglia.

PMID- 9654379
TI  - Neural dynamics of short and medium-term motor control effects of levodopa
      therapy in Parkinson's disease.
AB  - A neural network model of movement control in normal and Parkinson's disease (PD)
      conditions is proposed to simulate the time-varying dose-response relationship
      underlying the effects of levodopa on movement amplitude and movement duration in
      PD patients. Short and long-term dynamics of cell activations and
      neurotransmitter mechanisms underlying the differential expression of
      neuropeptide messenger RNA within the basal ganglia striatum are modeled to
      provide a mechanistic account for the effects of levodopa medication on motor
      performance (e.g. the pharmacodynamics). Experimental and neural network
      simulation data suggest that levodopa therapy in Parkinson's disease has
      differential effects on cell activities, striatal neuropeptides, and motor
      behavior. In particular, it is shown how dopamine depletion in the striatum may
      modulate differentially the level of substance P and enkephalin messenger RNA in
      the direct and indirect basal ganglia pathways. This dissociation in the
      magnitude and timing of peptide expression causes an imbalance in the opponently
      organized basal ganglia pathways which results in Parkinsonian motor deficits.
      The model is validated with experimental data obtained from handwriting movements
      performed by PD subjects before and after medication intake. The results suggest
      that fine motor control analysis and network modeling of the effects of dopamine
      in motor control are useful tools in drug development and in the optimization of
      pharmacological therapy in PD patients.

PMID- 9654380
TI  - Computer models of hippocampal circuit changes of the kindling model of epilepsy.
AB  - Abnormalities in the organization of brain circuits may underlie many types of
      epilepsy. This hypothesis can best be evaluated in the case of temporal lobe
      epilepsy, where evidence of rewiring (synaptic reorganization) can be found in
      the dentate gyrus. Computer modeling of normal and reorganized dentate gyrus was
      used to understand the functional consequences of these structural changes.
      Hyperexcitability appeared to be largely limited by the powerful intrinsic
      adaptation characteristic of granule cells, the principal cells in this area.
      Combining disinhibition with new recurrent excitatory circuitry was necessary to
      produce repeated firing of these cells. Paradoxically, continuing regenerative
      activity was only seen with a large reduction in the strength of the inciting
      stimulus. Validation of these findings will require further physiological
      correlation.

PMID- 9654381
TI  - Neuromodulatory control of hippocampal function: towards a model of Alzheimer's
      disease.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disorder of cognitive
      function whose cellular pathology and molecular etiology have been increasingly
      and dramatically unraveled over the last several years. Despite this substantial
      knowledge base, the disease remains poorly understood due to a basic lack of
      understanding of how memories are stored and recalled in the brain. We describe a
      preliminary attempt at constructing a detailed model of these basic neural
      mechanisms; in particular, the natural dynamics of neuronal activity in
      hippocampal region CA3 and the modulation and control of these dynamics by
      subcortical cholinergic and GABAergic input to the hippocampus. We view the
      construction of such a model, with sufficient detail at the cellular and
      subcellular level, to be a necessary first step in understanding the effect of AD
      pathology on the functional behavior of the underlying neural circuitry. The
      network is based on the 66-compartment hippocampal pyramidal cell model of Traub
      and colleagues and their 51-compartment interneuron interconnected with realistic
      AMPA-, NMDA-, and GABA(A)-mediated synapses. Traub and others have shown that a
      network composed of these modeled cells is capable of synchronization in the
      gamma frequency range. We demonstrate here that this synchronization mechanism
      can implement an attractor-based autoassociative memory. A new input pattern
      arrives at the beginning of each theta cycle (comprised of 5-10 gamma cycles),
      and the pattern of activity across the network converges, over several gamma
      cycles, to a stable attractor that represents the stored memory. In this model,
      cholinergic deprivation, one of the hallmarks of AD, leads to a slowing of the
      gamma frequency which reduces the number of "cycles" available to reach an
      attractor state. We suggest that this may be one mechanism underlying the memory
      loss and cognitive slowing seen in AD. Our results also support the idea that
      acetylcholine acts on individual neurons to induce and maintain a transition from
      intrinsic bursting to spiking in pyramidal cells. These results are consistent
      with the hypothesis that spiking and bursting in CA3 pyramidal cells mediate
      separate behavioral functions, and that cholinergic input is required for the
      transition to and support of behavioral states associated with the online
      processing and recall of information.

PMID- 9654382
TI  - An artificial neural network simulating performance of normal subjects and
      schizophrenics on the Wisconsin Card Sorting Test.
AB  - Mental diseases such as schizophrenia are being modeled by artificial neural
      networks in an attempt to understand the underlying neuropathological processes.
      We studied hospitalized psychiatric patients that met the DSM-IIIR criteria for
      schizophrenia (N=19), and normal subjects with no psychiatric history (N=18).
      Performance on the Wisconsin Card Sorting Test (WCST) by schizophrenic patients
      was poorer than normal subjects as estimated by various scoring measurements. We
      then modeled an artificial neural network, motivated by biological
      considerations, that is able to simulate performance of normals and
      schizophrenics on the WCST. In order to model the complex nature of the WCST, we
      designed novel learning rules based on non-associative learning paradigms. We
      found that there must be a minimum amount of noise, or inherent synaptic
      instability, for our model to perform similar to schizophrenics.

PMID- 9654383
TI  - Adenovirus in the brain: recent advances of gene therapy for neurodegenerative
      diseases.
AB  - Adenovirus is an efficient vector for neuronal gene therapy due to its ability to
      infect post-mitotic cells, its high efficacy of cell transduction and its low
      pathogenicity. Recombinant adenoviruses encoding for therapeutical agents can be
      delivered in vivo after direct intracerebral injection into specific brain areas.
      They can be transported in a retrograde manner from the injection site to the
      projection cell bodies offering promising applications for the specific targeting
      of selected neuronal populations not easily accessible by direct injection, such
      as the motor neurons in the spinal cord. Adenoviral vectors are also efficient
      tools for the ex vivo gene therapy, that is, the genetical modification of cells
      prior to their transplantation into the nervous system. Recently, the efficacy of
      the adenovirus as a gene vector system has been demonstrated in several models of
      neurodegenerative diseases including Parkinson's disease (PD) and motor neuron
      diseases. In rat models of PD, adenoviruses encoding for either tyrosine
      hydroxylase, superoxide dismutase or glial-derived neurotrophic factor improved
      the survival and the functional efficacy of dopaminergic cells. Similarly, the
      intramuscular injection of an adenovirus encoding for neurotrophin-3 had
      substantial therapeutic effects in a mutant mouse model of motor neuron
      degenerative disease. However, although adenoviruses are highly attractive for
      neuronal gene transfer, they can trigger a strong inflammatory reaction leading
      in particular to the destruction of infected cells. The recent development of new
      generations of adenoviral vectors could shed light on the nature of the immune
      reaction caused by adenoviral vectors in the brain. The use of these new vectors,
      combined with that of neurospecific and regulatable promoters, should improve
      adenovirus gene transfer into the central nervous system.

PMID- 9654384
TI  - Neural correlates of attention and arousal: insights from electrophysiology,
      functional neuroimaging and psychopharmacology.
AB  - Attention and arousal are multi-dimensional psychological processes, which
      interact closely with one another. The neural substrates of attention, as well as
      the interaction between arousal and attention, are discussed in this review.
      After a brief discussion of psychological and neuropsychological theories of
      attention, event-related potential correlates of attention are discussed.
      Essentially, attention acts to modulate stimulus-induced electrical potentials
      (N100/P100, P300, N400), rather than generating any unique potentials of its own.
      Functional neuroimaging studies of attentional orienting, selective attention,
      divided attention and sustained attention (and its inter-dependence on underlying
      levels of arousal) are then reviewed. A distinction is drawn between the brain
      areas which are crucially involved in the top-down modulation of attention (the
      'sources' of attention) and those sensory-association areas whose activity is
      modulated by attention (the 'sites' of attentional expression). Frontal and
      parietal (usually right-lateralised) cortices and thalamus are most often
      associated with the source of attentional modulation. Also, the use of functional
      neuroimaging to test explicit hypotheses about psychological theories of
      attention is emphasised. These experimental paradigms form the basis for a 'new
      generation' of functional imaging studies which exploit the dynamic aspect of
      imaging and demonstrate how it can be used as more than just a 'brain mapping'
      device. Finally, a review of psychopharmacological studies in healthy human
      volunteers outlines the contributions of the noradrenergic, cholinergic and
      dopaminergic neurotransmitter systems to the neurochemical modulation of human
      attention and arousal. While, noradrenergic and cholinergic systems are involved
      in 'low-level' aspects of attention (e.g. attentional orienting), the
      dopaminergic system is associated with more 'executive' aspects of attention such
      as attentional set-shifting or working memory.

PMID- 9654385
TI  - Basal ganglia organization in amphibians: evidence for a common pattern in
      tetrapods.
AB  - The results of recent studies investigating the connections and chemoarchitecture
      of the basal forebrain of amphibians provide strong evidence that tetrapod
      vertebrates share a common pattern of basal ganglia organization. This pattern
      includes the existence of dorsal and ventral striatopallidal systems, reciprocal
      connections between the striatopallidal complex and the diencephalic and
      mesencephalic basal plate (striato-nigral and nigro-striatal projections), and
      descending pathways from the striatopallidal system to the midbrain tectum and
      reticular formation. The connectional similarities are parallelled by
      similarities in the distribution of chemical markers of striatal and pallidal
      structures such as dopamine, substance P and enkephalin. Moreover, studies of
      development and expression of homeobox genes have given further support to the
      notion that both amniotic and anamniotic tetrapods have a common pattern of basal
      ganglia organization. A new nomenclature of basal forebrain structures in
      amphibians is proposed which reflects our current understanding of basal ganglia
      organization in this class of vertebrates.

PMID- 9654386
TI  - Viral vectors, tools for gene transfer in the nervous system.
AB  - Viral vectors are becoming increasingly important tools to investigate the
      function of neural proteins and to explore the feasibility of gene therapy to
      treat diseases of the nervous system. This gene transfer technology is based on
      the use of a virus as a gene delivery vehicle. In contrast to functional analysis
      of gene products in transgenic mouse, viral vectors can be applied to transfer
      genes to somatic, post-mitotic cells of fully developed animals. To date, five
      viral vector systems are available for gene transfer in the nervous system. These
      include recombinant and defective herpes viral vectors, adenoviral vectors, adeno
      associated viral vectors and lentiviral vectors. Of these vectors herpes and
      adenoviral vectors are the most common in use. To date, one of the main hurdles
      in applying these two vector systems is the focal immune response that occurs
      following intraparenchymal infusion. Despite this limitation, herpes and
      adenoviral vectors have been used successfully to modify the physiological
      response to injury in several rodent models of neurodegeneration. The first
      purpose of this review is to describe the principles of the generation of viral
      vectors and to discuss the advantages and disadvantages of the viral vector
      systems currently in use for gene transfer in the nervous system. Secondly, we
      give an overview of the performance of these vectors following direct infusion in
      the nervous system and review the results obtained with these vectors in animal
      models of neurodegeneration and regeneration. The results of these initial
      studies have provided a framework for future experiments based on gene transfer
      strategies with viral vectors to study normal physiology and pathology of the
      nervous system.

PMID- 9654387
TI  - The role of art in human life.

PMID- 9654388
TI  - Computers and medical education.

PMID- 9654389
TI  - Platelet-activating factor antagonism: a new concept in the management of
      regional myocardial ischemia-reperfusion injury.
AB  - Reperfusion therapies for treatment of myocardial infarction successfully reduce
      patient mortality; however, regional myocardial ischemia-reperfusion (RMIR)
      causes its own expression of cardiovascular dysfunction, including myocardial
      depression, hemodynamic instability, and dysrhythmias, which have increased
      patient mortality within the first 24 h after starting reperfusion therapy.
      Current evidence suggests that the release of oxygen-derived reactive substances
      and subsequent inflammatory mediators during ischemia-reperfusion contribute
      toward this injury. Platelet-activating factor (PAF), a mediator released during
      RMIR, has been emphasized by many investigators as playing a central role in
      causing RMIR injury. Similar cardiovascular dysfunctions that occur during RMIR,
      including myocardial depression, hemodynamic instability, and dysrhythmias, occur
      after administration of PAF and are ameliorated with PAF antagonists. Further,
      PAF antagonists have been shown to be cardioprotective and improve survival when
      administered before onset of reperfusion. A variety of phospholipid analogues,
      naturally derived compounds, and synthetic compounds have been developed that
      form the different classes of PAF antagonists, each with unique antagonizing
      properties. Several of these compounds have successfully passed safety and
      efficacy testing in humans; however, to date, no clinical trials have
      investigated the protective effects of PAF antagonists against RMIR injury. A
      current theory in the pathogenesis of RMIR injury considers the ischemic and
      necrotic portion of the myocardium and regional dysfunction due to tissue
      necrosis to be solely responsible for global cardiac dysfunction leading to
      hemodynamic instability and death. Evidence now suggests, however, that the
      global dysfunction is also due to the effect of inflammatory mediators such as
      PAF, thromboxanes, leukotrienes, and endothelins that are released during RMIR
      and are distributed throughout the heart on reperfusion. Antagonizing a central
      inflammatory mediator such as PAF, as adjunct treatment with currently used
      reperfusion therapies, improves cardiovascular function and survival in animals
      and should be introduced into clinical trials to investigate if similar
      protective effects can be provided in humans.

PMID- 9654390
TI  - The role of electrolyte in lesion size using an irrigated radiofrequency
      electrode.
AB  - Multiple attempts have been made to eliminate atrial fibrillation by performing
      the surgical maze procedure with radiofrequency energy. Currently, this is
      limited because of the risk of atrial perforation and the lack of transmural
      penetration. Saline irrigation has been investigated as a method of
      radiofrequency cautery tip cooling to prevent rapid temperature and impedance
      rises, which have been shown to lead to perforation or decreased radiofrequency
      penetration after eschar formation. There are few data on the influence that
      different types of electrolyte irrigation solutions have on lesion depth. Using a
      novel hollow cautery pen, we infused either an electrolyte solution (0.9%, 3%,
      14.6%, or 23.4% sodium chloride), a nonelectrolyte solution (1.5% glycine), or no
      irrigation to produce 819 lesions on 14 left ventricles in swine using
      radiofrequency energy (450+/-10 kHz) applied at two output settings (20 and 75
      watts). The nonelectrolyte solution increased lesion depth compared with no
      infusion at 20 watts but produced shallower lesion depths compared with
      electrolyte solutions at 75 watts. Compared with the other electrolyte solutions,
      the 0.9% sodium chloride solution produced the deepest lesions (3.34+/-0.06 mm)
      at 75 watts (p < 0.001). As the concentration of electrolyte increased, lesion
      depth decreased unless generator output increased. Formation of eschar and tissue
      destruction was seen in the noninfusion and nonelectrolyte groups but not in the
      electrolyte group. A conductive media coupled with radiofrequency energy allowed
      for greater lesion depth than irrigated cooling with a nonelectrolyte solution or
      no irrigation. There was an inverse relationship between electrolyte
      concentration and lesion depth. We conclude that the concentration of electrolyte
      irrigant is an important consideration when choosing a solution to improve
      transmural penetration and decrease the risk of tissue destruction from
      radiofrequency energy.

PMID- 9654391
TI  - Depression of tumor necrosis factor-alpha, interleukin-6, and interleukin-10
      production: a reaction to the initial systemic hyperactivation in septic shock.
AB  - Sepsis remains a major cause of mortality in surgical intensive care units.
      Patients who survive the initial shock phase but die weeks later from multiple
      organ dysfunction still are a challenge to basic and clinical research. We
      addressed whether fulminant sepsis results in rapid changes (24 h) in the
      cellular capacity to produce cytokines in whole blood of septic patients on
      further stimulation after the initial systemic inflammatory response. Interleukin
      (IL)-6 plasma concentrations from 279 pg/mL to 5979 pg/mL confirmed the presence
      of a systemic inflammatory response. Anti-inflammatory IL-10 concentrations up to
      275 pg/mL were detected, but there was no biologically active tumor necrosis
      factor-alpha (TNFalpha) detectable (by bioassay) at the time of investigation. On
      stimulation with Escherichia coli ex vivo, pro-inflammatory TNFalpha (130 pg/mL),
      IL-6 (4061 pg/mL), and anti-inflammatory IL-10 (711 pg/mL) production were
      markedly depressed in all patients compared with controls (2339 pg/mL, 50,319
      pg/mL, and 9654 pg/mL, respectively). Septic shock resulted in early depression
      of the capacity for pro- and anti-inflammatory cytokine production. Monitoring of
      this effect, including its relationship to outcome, may offer a target variable
      for therapeutic efforts to maintain or restore adequate immune reactions to
      improve survival.

PMID- 9654392
TI  - Perfluorocarbons: future clinical possibilities.
AB  - Perfluorocarbons are now being used as oxygen carriers in clinical settings.
      Because these chemicals may have a role as a blood substitute, in organ
      preservation, and in the management of respiratory failure, we have reviewed some
      of the research leading to these applications.

PMID- 9654393
TI  - Prevention of adhesion formation with intraperitoneal administration of tolmetin
      and hyaluronic acid.
AB  - Adhesion formation after peritoneal surgery is a major source of postoperative
      complications and pain. Previous studies showed that intraperitoneal
      administration of the nonsteroidal anti-inflammatory drug tolmetin reduced
      adhesion formation after two types of peritoneal surgery. The effect of tolmetin
      combined with hyaluronic acid (HA), a high-molecular-weight glucosaminoglycan
      found in the extracellular matrix, on the formation of adhesions was examined. In
      this study, the effect of tolmetin in HA on adhesion formation was evaluated in a
      standardized rabbit model. The medicament was administered intraperitoneally at
      the end of surgery. One week after surgery, a second laparotomy was performed and
      the extent of adhesion formation was determined. A range of molecular weights
      (7.5 x 10(5)-2 x 10(6) Da) and viscosities (1000-25,000 centapoise) of HA in
      combination with tolmetin was effective in reducing adhesion formation. However,
      low viscosity HA solutions in combination with tolmetin, 0.5-2.0 mg/mL, were most
      efficacious in reducing adhesion formation. These data suggest that HA, in
      combination with tolmetin, acts as an effective carrier to reduce adhesion
      formation in the abdominal cavity after surgery.

PMID- 9654394
TI  - Graft length affects outcome in fetal small bowel transplants.
AB  - Multiple studies have demonstrated the ability of the fetal rat small intestine
      to be transplanted successfully as a free graft, devoid of its mesentery. While
      maintaining normal histologic architecture, portal circulation, and digestive and
      absorptive properties, the initial myeloelectric activity is delayed. The purpose
      of this study was to investigate how abnormal early motility affects functional
      outcome and survival. Using a syngeneic model, fetal rat small intestine segments
      were transplanted into adolescent rat recipients as free grafts into the omentum.
      After a maturation period, viable segments measuring 1 or 2 cm were placed into
      continuity with the native intestine after a standardized resection of either
      jejunum-ileum, ileum-cecum, or cecum. Control animals had native intestinal
      resection without graft interposition. Survival, daily weight gain, oral intake,
      and fecal output were monitored. In this model, overall survival was improved
      with the use of the shorter 1-cm graft segment compared with the 2-cm and more
      distal interpositions. No animals survived with proximal graft placement after
      jejunal-ileal resection. Nutrient use was improved in the transplant recipients
      compared with nontransplant controls but did not differ between the two graft
      lengths. These data suggest that outcome in this model is improved using shorter
      fetal intestine graft lengths. The use of multiple segments in multistaged
      procedures and early defunctionalization may improve results.

PMID- 9654395
TI  - Mechanical characteristics of four allograft tendon-to-muscle anastomotic
      techniques.
AB  - Four methods of allograft tendon-to-muscle anastomosis were tested in single
      cycle distraction to failure using 10 anastomosed ovine calcaneal tendon-biceps
      brachii units. The tendon-muscle units were compared to intact ovine biceps
      brachii muscle units. Methods of tendon-to-muscle anastomosis were derived from
      modifications of existing muscle tendon repair and tenorrhaphy techniques. Load
      to failure (N), stiffness (N/cm), distraction (cm), and modes of failure were
      recorded. Of the four methods tested, the side-to-side technique demonstrated the
      highest load to failure (152.1 N), the greatest stiffness (17.6 N/cm), the least
      distraction (2.99 cm) before failure, and the least amount of muscle tissue
      trauma at failure. Results indicate that, of the methods tested, the side-to-side
      technique offers the greatest initial stability and should therefore allow
      adequate revascularization and healing of the anastomosis site.

PMID- 9654396
TI  - Experimental cardiomyopathy as a model of chronic heart failure.
AB  - End-stage heart disease is a major health care issue and it represents one of the
      most costly diseases. Several experimental heart failure models have been
      developed; however, a single model is not widely accepted as representative of
      clinical heart failure. The doxorubicin-induced cardiomyopathy model was used in
      the current study to address two issues: 1) to define a standardized dose regimen
      of intracoronary doxorubicin infusion; and 2) to establish a method of
      determining the onset and time course of heart failure. Twenty dogs underwent
      placement of an intracoronary catheter. A total dose of 1 mg/kg of intracoronary
      doxorubicin was infused. Hemodynamics were obtained at weeks 0, 7, and 12.
      Echocardiography was performed weekly. Right and left ventricular biopsy
      specimens were examined at weeks 0 and 12. Survival after doxorubicin-induced
      cardiomyopathy was 60% at week 12. The development of heart failure was
      demonstrated by a significant decrease in left ventricular ejection fraction and
      cardiac index and a significant increase in left ventricular end-diastolic
      pressure and volume. The leukocyte count, hemoglobin, and hematocrit decreased
      significantly. Histologic changes of both the right and left ventricular
      myocardial biopsy specimens included myocellular hypertrophy, loss of
      myofibrillar material, and vacuolization. Intracoronary doxorubicin reliably
      produced an experimental model of accelerated heart failure that developed over
      the course of 12 weeks. Echocardiographic monitoring allowed a close surveillance
      of heart failure development. This model may be useful to evaluate the efficacy
      of cardiomyoplasty, mechanical assist devices, transplantation, and reduction
      ventriculoplasty.

PMID- 9654397
TI  - Effects of low chronic ethanol exposure on prostaglandin E synthesis by
      preimplantation mouse embryos.
AB  - Embryo prostaglandin (PG) synthesis plays a role in the modulation of embryo
      metabolism and viability, and in the beginning of the implantation. The effects
      of ethanol consumption seem to be mediated at least in part by PGs. Increased PG
      production of postimplantation embryos is associated with retardation and
      abnormalities in the gestational period. The aim of this study was to find out
      the effects of low chronic ethanol ingestion by mice, previous to pregnancy, on
      the PGE released by in vitro and in vivo derived embryos. Immature females or
      adult males were treated with 5% ethanol for 30 days. After fertilization and
      mating, two-cell embryos, morulae and blastocysts were collected. The PGE
      synthesis and release were measured by radioimmunoassay. PGE production by in
      vitro derived two-cell embryos from ethanol-treated females was lower than in the
      control group (P < 0.01). Also, PGE production was reduced when two-cell embryos
      came from ethanol-treated males (P < 0.01). There were no differences in PGE
      synthesis by in vitro derived morulae and blastocysts in these groups. Two-cell
      embryos derived from mating produced lower quantities of PGE when they came from
      ethanol-treated females mated with control males, as compared to the control
      group. PGE release by in vivo derived blastocysts from ethanol-treated females
      was reduced significantly, as compared to the control group (P < 0.01). We
      conclude that a low concentration of ethanol administered chronically to immature
      females reduces PGE synthesis and release by two-cell embryos from culture in
      vitro, and by embryos of days 2 and 4 from in vivo development.

PMID- 9654398
TI  - Effect of garlic (Allium sativum) on blood lipids, blood sugar, fibrinogen and
      fibrinolytic activity in patients with coronary artery disease.
AB  - Thirty patients with coronary artery disease (CAD) were administered garlic
      (study group) while another 30 patients received the placebo (control group).
      Various risk parameters were determined at 1.5 and 3 months of garlic
      administration. Garlic, administered in a daily dose of 2 x 2 capsules (each
      capsule containing ethyl acetate extract from 1 g peeled and crushed raw garlic),
      reduced significantly total serum cholesterol and triglycerides, and increased
      significantly HDL-cholesterol and fibrinolytic activity. There was no effect on
      the fibrinogen and glucose levels. In vitro effects of the garlic oil on platelet
      aggregation (PAg) and eicosanoid metabolism were examined; it inhibited PAg
      induced by several platelet agonists, and also platelet thromboxane formation.
      Two important paraffinic polysulphides - diallyl disulphide (DADS) and diallyl
      trisulphide (DATS) - derived from garlic and are usual constituents of garlic
      oil, showed antiplatelet activity, and also inhibited platelet thromboxane
      formation. In this respect DATS was more potent than DADS. The nature of
      inhibition of PAg by DATS was found to be reversible.

PMID- 9654399
TI  - Inhibition of leukotriene synthesis by terfenadine in vitro.
AB  - To determine the inhibitory mechanisms of terfenadine on the synthesis of
      leukotriene C4 (LTC4), an important mediator in allergic diseases, we evaluated
      the action of terfenadine on the IgE-dependent production of LTC4 in rat
      basophilic leukaemia 2H3 cells. Rat IgE-loaded cells were stimulated with anti
      IgE in the presence or absence of various concentrations of terfenadine and the
      level of LTC4 released into the medium was measured by performing a specific
      radio immunoassay. Terfenadine inhibited the synthesis of LTC4 to 67.2% at a
      concentration of 5 microg/ml. LT synthesis was directly suppressed by inhibition
      of 5-lipoxygenase (5-LO) through calcium ion-independent mechanisms, and was also
      possibly suppressed by inhibition of cytosolic phospholipase A2 and 5-LO by
      blocking the influx of intracellular calcium ion that was initiated by IgE
      related stimulation.

PMID- 9654400
TI  - Inhibition of EGF-dependent mitogenesis by prostaglandin E2 in Syrian hamster
      embryo fibroblasts.
AB  - Lipid metabolism can play an important role in the development and progression of
      human cancers. We have used Syrian hamster embryo (SHE) fibroblasts as a model
      system to study how lipid metabolites can alter cell proliferation and apoptosis.
      For example, the linoleic acid metabolite 13(S)-HpODE enhances EGF-dependent
      growth by inhibiting de-phosphorylation of the EGFR which leads to activation of
      the MAP kinase pathway. In contrast, the arachidonic acid metabolite, PGE2,
      inhibits EGF-dependent mitogenesis and the expression of the proto-oncogenes c
      myc, c-jun, and jun-B. In this study, we have investigated the mechanism by which
      PGE2 attenuates these responses by studying the EGF signaling cascade in SHE
      cells. PGE2 pretreatment caused a concentration-dependent decrease in EGF
      dependent phosphorylation of MAP kinase and a corresponding inhibition of EGF
      stimulated MAP kinase activity. Pretreatment of the SHE cells with PGE2 had
      little effect on the magnitude of EGF-dependent receptor auto-phosphorylation and
      the phosphorylation of GAP suggesting a down-stream target. Treatment of cells
      with forskolin and EGF causes similar inhibition of MAP kinase phosphorylation as
      observed with PGE2 and EGF. Since PGE2 elevates cAMP in these cells, it may act
      by altering cAMP accumulation. Raf-1 activity can be inhibited by a cAMP
      dependent process. Raf-1 activity, measured by phosphorylation of Mek-1, was
      attenuated by the addition of PGE2. To determine if inhibition of Raf-1 activity
      causes inhibition of the MAP kinase pathway, cells were concomitantly incubated
      with PGE2 and EGF. Inhibition of MAP kinase phosphorylation was observed. From
      these data, we propose that in SHE cells PGE2 increases cAMP levels, which in
      turn causes inhibition of Raf-1 activity. The MAP kinase pathway is thus
      downregulated which decreases mitogenesis and proto-oncogene expression. This
      study demonstrates that an arachidonic acid metabolite can modulate
      phosphorylation and activity of key signal transduction proteins in a growth
      factor mitogenic pathway.

PMID- 9654401
TI  - In vitro activity of polyunsaturated fatty acids on Pseudomonas aeruginosa:
      relationship to lipid peroxidation.
AB  - Based on previous findings that gamma-linolenic acid (GLA) inhibits Escherichia
      coli growth and provokes the induction of strains resistant to aminoglycosides,
      19 Pseudomonas aeruginosa strains were exposed in vitro over time to GLA, to
      arachidonic acid (AA) and to their combination in the presence or absence of
      vitamin E. All acids were used at a 300 microg/ml concentration, whereas vitamin
      E was added as an antioxidant. Lipid peroxidation was evaluated by the
      thiobarbiturate assay measuring malonodialdehyde (MDA) production. It was found
      that GLA or AA killed 5-10% of strains at 24 h of growth, whereas when applied in
      combination their effect involved 100% of strains at 24 h and was limited to 68%
      of strains in the presence of vitamin E (P< 0.01). MDA production was time
      dependent and it was restrained by vitamin E (P < 0.01). Post acid exposure, 27%
      to 37% of the survived strains became resistant to diverse antimicrobial agents
      and mainly to ticarcillin, to ceftazidime and to amikacin; no strain developed
      resistance in the presence of vitamin E. It is concluded that GLA and AA interact
      bactericidally on P. aeruginosa isolates, inducing the development of strains
      resistant to beta-lactams and to aminoglycosides; their action might be mediated
      through their peroxides. Further research is necessary to establish the clinical
      application of these in vitro findings.

PMID- 9654402
TI  - Effect of dietary n-3 fatty acids on interleukin-2 and interleukin-2 receptor
      alpha expression in activated murine lymphocytes.
AB  - Dietary eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) suppress
      interleukin-2 (IL-2) secretion and impair T-lymphocyte proliferation. To
      determine the mechanism of action, mice were fed diets containing either
      safflower oil (control diet enriched in linoleic acid, 18:2n-6), EPA, DHA or
      arachidonic acid (20:4n-6). Splenic lymphocytes were isolated and concanavalin A
      induced kinetics of IL-2 and IL-2 receptor alpha mRNA expression were determined
      by relative competitive-PCR. EPA and DHA did not affect IL-2 mRNA expression but
      suppressed IL-2 receptor alpha mRNA levels. These data show, for the first time,
      the selective effects of dietary EPA and DHA on T-lymphocyte gene expression.

PMID- 9654403
TI  - Induction of apoptosis, p53 and heme oxygenase-1 by cytotoxic prostaglandin
      delta12-PGJ2 in transformed endothelial cells.
AB  - Delta12-prostaglandin (PG)J2, which has been reported to have potent growth
      inhibitory activity in various tumor cells, induced apoptosis at 5 microg/ml
      culture medium in transformed mouse endothelial (F2) cells. Immunoblot analysis
      using anti-p53 or anti-WAF1 antibodies demonstrated that these two proteins had
      increased following delta12-PGJ2 treatment in F2 cells. Western blotting analysis
      using anti-heme oxygenase-1 (heat shock protein (HSP)32) antibody also revealed
      that delta12-PGJ2 induced HSP32 formation in F2 cells. HSP32 was also induced by
      heat shock treatment at 43 degrees C for 90 min. In contrast, HSP72 was not
      induced by heat shock or by delta12-PGJ2 treatment. In agreement with these
      findings, HSP32 immunofluorescence in the cytoplasm of F2 cells was intensified
      by delta12-PGJ2 treatment. More intense HSP32 immunoreactivity was similarly
      observed after heat shock treatment. These results suggest that delta12-PGJ2
      caused the apoptotic cell death of F2 cells, which involved a certain process
      required for p53 or HSP32 induction.

PMID- 9654404
TI  - Dietary n-3 fatty acids alter angiotensin-induced contraction and 1,2
      diacylglycerol fatty acid composition in thoracic aortas from diabetic rats.
AB  - The effect of diabetes on the incorporation of long-chain n-3 fatty acids into
      thoracic aorta smooth muscle phospholipids and 1,2-diacylglycerol, and on the
      contractile response of aortic rings to angiotensin II, was examined in
      streptozotocin-induced diabetic rats. In diabetic animals fed a diet containing
      1% of fatty acids as n-3 fatty acids, smooth muscle membrane levels of 18:2n-6
      were elevated in phosphatidylcholine, phosphatidylethanolamine and
      phosphatidylinositol, whereas 20:4n-6 was depleted. The resultant decreased
      ratios of 20:3/18:2 and 20:4/20:3 indicate inhibition of delta6- and delta5
      desaturase activity in the diabetic state. A diet containing 5% of fatty acids as
      n-3 fatty acids increased phospholipid levels of eicospentaenoic acid (EPA),
      docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) several-fold, but with
      a further reduction in 20:4n-6. Similarly, 1,2-diacylglycerol from rats fed the
      high n-3 diet was enriched in EPA, DPA and DHA. When incubated with 10(-8) M
      angiotensin II, the contractile response of intact aortic rings from diabetic
      animals fed the high n-3 diet was only 60.8+/-9.3% that of controls fed the same
      diet. However, contractile response was not significantly different from control
      animals fed the low n-3 diet (55.6+/-7.9%). The results indicate that vascular
      smooth muscle phospholipid n-6 and n-3 fatty acid metabolism is altered in
      diabetes, resulting in changes to the fatty acid profile of 1,2-diacylglycerol.
      Moreover, elevating membrane phospholipid and 1,2-diacylglycerol content of EPA,
      DPA and DHA partially ameliorates the depressed response to angiotensin II seen
      in the diabetic state.

PMID- 9654405
TI  - Tumor metastasis inhibition with the prostacyclin analogue cicaprost depends on
      discontinuous plasma peak levels.
AB  - Stable prostacyclin analogues exert a strong inhibitory effect on lymphogenous as
      well as haematogenous tumor metastasis in a series of tumor lines. The strong
      inhibition of metastasis was achieved by repeated once-daily i.g. applications.
      The mechanism of antimetastatic action is related to the expression of functional
      IP-receptors (PGI-receptors). As cellular assay systems indicated that the IP
      receptor mediated signalling is down-regulated upon continuous exposure to
      prostacyclin or stable derivatives, it has been questioned whether a mode of drug
      application with constant plasma drug levels may potentially result in a decrease
      of the antimetastatic effect. We addressed this question using the stable
      prostacyclin analogue cicaprost in a disease model by comparing i.g. applications
      given once daily with a continuous administration of equivalent doses via
      drinking water. Very similar to our previous investigations in the 13762NF MTLn3
      rat mammary carcinoma model, cicaprost administered by i.g. application strongly
      reduced lung and lymph node metastasis. In contrast, administration of equivalent
      doses via drinking water leading to lower but constant steady-state plasma levels
      failed to exert inhibitory effects. Plasma and urine levels of cicaprost were
      measured with a sensitive radioimmunoassay on the last treatment day.
      Pharmacokinetic evaluation demonstrated a similar bioavailability of cicaprost in
      both groups. This result first demonstrates a treatment failure of a prostacyclin
      derivative in a chronic disease model in association with a continuous drug
      administration leading to constant plasma levels. A desensitization of receptor
      signalling by constant plasma levels may be a possible mechanism for treatment
      failure.

PMID- 9654406
TI  - Radioimmunoassay of 8-iso-prostaglandin F2alpha: an index for oxidative injury
      via free radical catalysed lipid peroxidation.
AB  - 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha), a major F2-isoprostane, is
      biosynthesized in vivo through nonenzymatic free radical-catalysed peroxidation
      of arachidonic acid. The levels of F2-isoprostanes both free in the circulation
      and esterified to the tissue phospholipids increase intensely in animal models of
      oxidant injury. This study presents the development and validation of a
      radioimmunoassay of 8-iso-PGF2alpha for the measurement of this substance in the
      body fluids. Furthermore, its application in normal human volunteers, a
      pharmacokinetic study performed in rabbits with 8-iso-PGF2alpha, and hepatic
      lipid peroxidation in rats is reported. An antibody was raised in rabbits by
      immunization with 8-iso-PGF2alpha coupled to BSA at the carboxylic acid by 1,1'
      Carbonyldiimmidazole method. The cross-reactivity of the antibody with 8-iso-15
      keto-13,14-dihydro-PGF2alpha, 8-iso-PGF2beta, PGF2alpha, 15-keto-PGF2alpha, 15
      keto-13,14-dihydro-PGF2alpha,TXB2, 11beta-PGF2alpha, 9beta-PGF2alpha and 8-iso
      PGF3alpha was 1.7, 9.8, 1.1, 0.01, 0.01, 0.1, 0.03, 1.8 and 0.6%, respectively.
      The intraassay precision was 14.5% (CV) at the level of 64 pg/0.1 ml and 12.2%
      with 512 pg/0.1 ml in the human plasma. Similarly, intra-assay accuracy was 95.6%
      and 101% for the low and the high standard, respectively. The detection limit was
      about 23 pmol/l. The appearance and disappearance of 8-iso-PGF2alpha in the blood
      and urine following intravenous administration of 8-iso-PGF2alpha in the rabbit
      was rapid. Free 8-iso-PGF2alpha levels in plasma and urine from normal human
      volunteers are evaluated and found to correlate with the obtained values by gas
      chromatography-mass spectrometry methods from other studies. The levels of free 8
      iso-PGF2alpha in the plasma and urine increased 7- and 102-fold, respectively,
      after CCl4 administration to rats. Thus, this 8-iso PGF2alpha radioimmunoassay
      method is relevant to apply in the oxidative injury studies as an index of in
      vivo lipid peroxidation through free radical catalysis mechanism.

PMID- 9654407
TI  - Effect of gammalinolenic acid, dihomogammalinolenic acid, ascorbyl-6
      gammalinolenic acid, and ascorbyl-6-dihomo gammalinolenic acid on histamine- and
      methacholine-induced contraction of the isolated guinea pig tracheal chain.
AB  - The relaxant effects of gammalinolenic acid (GLA) and dihomo gammalinolenic acid
      (DGLA) were compared to the relaxant effect of arachidonic acid (AA). The effect
      of the combination of ascorbate to form the novel drugs ascorbyl-6-gammalinolenic
      acid (ascorbyl-6-GLA) and ascorbyl-6-dihomo gammalinolenic acid (ascorbyl-6-DGLA)
      were investigated and the role of the epithelial cells was determined. Salbutamol
      was used as control. The isolated tracheas of six to eight guinea pigs were used
      in each experiment and suspended in organ baths filled with Krebs-Henseleit
      solution and aerated with 95% O2 and 5% CO2. The relaxant effects produced for
      histamine-contracted preparations were as follows: AA=71.2+/-0.2%, GLA=55.2+/
      4.2%, DGLA=69.8+/-3.9%, ascorbyl-6-GLA =26.2+/-5.1% and ascorbyl-6-DGLA=54.5+/
      2.4%. For methacholine-contracted preparations: AA=46.6+/-3.2%, GLA=55.0+/-9.5%,
      DGLA=61.8+/-2.7%, ascorbyl-6-GLA=40.0+/-8.0% and ascorbyl-6-DGLA=88.0+/-15.3%.
      Ascorbyl-6-GLA and ascorbyl-6-DGLA had mainly a decreased relaxant effect
      compared to GLA and DGLA, except ascorbyl-6-DGLA after methacholine-induced
      contraction, which showed a significant increased relaxant effect. The removal of
      the epithelium showed decreased relaxant effects for the drugs except AA, which
      showed increased values after methacholine contraction. Histamine-contracted
      preparations showed varied results. Ascorbyl-6-GLA showed an increased relaxant
      effect, DGLA was unaffected with no additional effect, and AA, GLA and ascorbyl-6
      DGLA showed decreased relaxant effects. In conclusion, it is clear that the
      contractant and the availability of epithelial cells could ultimately determine
      the results, though the mechanism remains very complex. The benefit of added
      ascorbate is still unclear and warrants more investigation.

PMID- 9654408
TI  - Wanted: optimal data regarding surgery for retinal detachment.

PMID- 9654409
TI  - A tribute to Robert Machemer, MD, on the occasion of his retirement.

PMID- 9654410
TI  - Histoplasmosis-like choroiditis in a nonendemic area: the northwest United
      States.
AB  - PURPOSE: Histoplasmosis is not endemic in the U.S. northwest, but a type of
      multifocal choroiditis resembling ocular histoplasmosis occurs there. This study
      was designed to find a group of affected patients and study their clinical
      characteristics and immunologic responses to Histoplasma antigens. METHOD: Ten
      patients were found in the authors' files whose geographic histories made it
      unlikely that they had ever been exposed to Histoplasma capsulatum and yet they
      had features of ocular histoplasmosis. They were recalled for examination and
      testing by lymphocyte-stimulation assay for previous exposure to histoplasmosis.
      RESULTS: The clinical features of these patients resembled those of patients with
      ocular histoplasmosis, but their histories and the results of the assay did not
      support H. capsulatum as the cause of the ocular disease. CONCLUSION: This study
      confirmed that there is a type of choroiditis that resembles ocular
      histoplasmosis but is due to another agent or agents.

PMID- 9654411
TI  - Management of glass intraocular foreign bodies.
AB  - PURPOSE: To describe the results of management of glass intraocular foreign
      bodies (IOFBs). METHODS: A total of 51 eyes of 43 patients that sustained
      penetrating injury with glass IOFB were studied retrospectively. A total of 23.5%
      had IOFB only in the anterior segment; the rest had IOFB in the posterior segment
      alone or in both the anterior and posterior segments. Six eyes were followed
      conservatively despite IOFB in a functional eye. Removal of IOFB was combined
      with repair of retinal detachment (where present) using internal tamponade with
      gas or silicone oil or buckle. RESULTS: After a mean follow-up of 16.8 months,
      66.7% of eyes recovered better than 6/60 (20/200) vision and 75.6% had attached
      retina. On univariate analysis, scleral entry wound, posterior segment IOFB,
      larger size of IOFB, and retinal damage were found to be associated with poor
      anatomic outcome. Lower presenting visual acuity, hyphema, retinal damage,
      subretinal hemorrhage, detached retina, and larger IOFB were associated with a
      poor functional result. Multivariate analysis identified retinal damage caused by
      the foreign body as the only factor significantly associated with poor anatomic
      as well as functional outcome. CONCLUSIONS: Glass IOFBs are caused in a majority
      of cases by blast injury. Bilaterality is not uncommon. Presence of retinal
      damage is predictive of poor functional and anatomic results. Overall results are
      modest with modern vitreoretinal surgical techniques.

PMID- 9654412
TI  - Vitrectomy and silicone oil injection in pediatric patients.
AB  - OBJECTIVE: To determine the functional and anatomic results of vitrectomy with
      silicone oil injection in complicated retinal detachments in children. DESIGN: A
      retrospective review of all records of children aged 15 years or younger who
      underwent vitrectomy with silicone oil injection between 1985 and 1994 in the
      Goldschleger eye institute. RESULTS: Twenty-eight eyes of 27 patients were
      included in the series, with a mean follow-up time of 24 months. The underlying
      pathologies included penetrating injury (11 eyes), high myopia (8 eyes),
      choroidal coloboma (2 eyes), retinopathy of prematurity (2 eyes), and various
      other pathologies (5 eyes). At the end of the follow-up, complete or partial
      anatomic success was obtained in 9 eyes (32%) and 3 eyes (10%), respectively. The
      final visual acuity was 20/400 or better in 5 eyes (18%) and hand motions or less
      in 19 eyes (68%). The visual acuity could not be determined in 3 eyes due to the
      age of the patients, and in 1 eye due to mental retardation. The worst results
      occurred in the perforating injury group. The usual complications associated with
      silicone oil occurred frequently. CONCLUSIONS: Satisfactory anatomic and
      functional results were obtained in a minority of the eyes included in our
      series. The grave prognosis was determined by the devastating nature of the
      external injury in the trauma cases and the severe vitreoretinal pathology in the
      other eyes.

PMID- 9654413
TI  - Silicone oil removal combined with macular pucker dissection: a retrospective
      review of 14 cases.
AB  - PURPOSE: Silicone oil must be removed from the eye to avoid late complications
      after the surgical management of proliferative vitreoretinopathy (PVR). Macular
      pucker, frequently observed after retinal detachment surgery, is responsible for
      visual impairment. The safety of a procedure combining epimacular membrane
      peeling and silicone oil removal was retrospectively evaluated. METHODS: Fourteen
      eyes that had previously undergone vitrectomy and silicone oil tamponade for
      rhegmatogenous retinal detachment with severe PVR, penetrating or blunt trauma,
      and intraocular foreign bodies were included. Silicone oil tamponade was
      maintained for a mean period of 30 weeks (range, 12-108 weeks). The removal of
      silicone oil was combined with the peeling of an epimacular membrane. RESULTS:
      Mean follow-up after silicone oil removal was 86 weeks (range, 13-234 weeks). The
      final retinal reattachment rate was 78%. Macular pucker recurred in one eye after
      a 24-month period. Best-corrected visual acuity improved two lines or more in
      eight eyes (57%) and reached 20/200 or better in eight eyes (57%) at last follow
      up. CONCLUSION: Macular pucker dissection and silicone oil removal can be safely
      combined. This single procedure can obviate the need for further surgery in eyes
      that have already undergone multiple operations and allows good visual recovery.

PMID- 9654414
TI  - Long-term follow-up of perfluorocarbon liquid in the anterior chamber.
AB  - BACKGROUND: Perfluorocarbon liquids are used as a vitreous substitute in the
      operative management of several ophthalmologic conditions. We examined the
      effects of residual perfluorocarbon droplets in the anterior chamber in patients
      after retinal detachment surgery. METHODS: The study group consisted of seven
      patients (seven eyes) aged 28-74 years in whom droplets of perfluorocarbon
      appeared in the anterior chamber subsequent to retinal detachment surgery
      involving scleral buckling, perfluorodecalin injection, and perfluorocarbon
      liquid-silicone oil exchange. Mean follow-up was 9.4 months. RESULTS: From 1 -15
      droplets of perfluorocarbon liquid were found in the anterior chamber. There were
      no corneal complications or inflammatory reactions or blood vessel invasion into
      the corneal stroma. Some of the droplets appeared to be encapsulated in a
      membrane-like material. Perfluorocarbon liquid and silicone oil had to be removed
      in three patients at 20, 12, and 4 months postoperatively because of an increase
      in intraocular pressure due to blockage of the inferior iridectomy by a droplet
      of perfluorocarbon, emulsification of the silicone oil, or residual
      perfluorocarbon liquid on the retina (one patient each). Increased intraocular
      pressure in a fourth patient was successfully treated pharmacologically.
      CONCLUSION: Based on our experience, residual perfluorocarbon liquid droplets in
      the anterior chamber are well tolerated and do not induce corneal damage or
      ocular inflammation. These patients should be closely followed, however, and the
      liquid removed if complications develop.

PMID- 9654415
TI  - Diffuse anterior retinoblastoma.
AB  - PURPOSE: The authors describe the clinicopathologic features of an anterior
      variant of diffuse retinoblastoma. METHODS: The clinical history of a child with
      an anterior chamber infiltrate and cells in the anterior vitreous was reviewed.
      An anterior chamber aspirate was processed by a Millipore filter technique. The
      eye was enucleated and routinely processed for light and transmission electron
      microscopic examination. RESULTS: An 8-year-old girl was treated for anterior
      uveitis in her right eye that failed to resolve. Examination of an anterior
      chamber aspirate showed cells suggestive of retinoblastoma. The eye was
      enucleated, and the enucleation specimen showed retinoblastoma confined to the
      iris, ciliary body, and anterior vitreous with one microscopic focus of tumor in
      the peripheral retina. CONCLUSION: This variant of diffuse retinoblastoma
      involved only anterior ocular structures with minimal involvement of the retina.

PMID- 9654416
TI  - Photocoagulation of well-defined choroidal neovascularization in age-related
      macular degeneration: clinicopathologic correlation.
AB  - PURPOSE: To present the clinicopathologic features of the eyes of a patient with
      age-related macular degeneration (ARMD): the right eye was treated for well
      defined extrafoveal choroidal neovascularization (CNV), and the left eye had an
      untreated disciform scar. METHODS: The patient was studied ophthalmoscopically
      and by fluorescein angiography at the time of presentation and on follow-up
      examinations up to 54 days after laser treatment, when he died. The posterior
      portions of both eyes (obtained postmortem), including the macula and optic nerve
      head, were sectioned serially for light microscopy. Tissue sections from both
      eyes were removed from glass slides and studied by transmission electron
      microscopy. RESULTS: Histopathologic study of the right eye disclosed a thin
      layer of basal laminar deposit throughout the posterior pole. Two defects in
      Bruch's membrane without CNV were present within the area of laser
      photocoagulation located superior to the fovea. No CNV was present in the scar.
      Eleven areas of early CNV were present in the posterior pole. Histopathologic
      study of the left eye showed a prominent basal laminar deposit throughout the
      posterior pole. A 2.6 x 2.7 mm disciform scar was present that was located mostly
      in the subretinal space. Four sources of CNV were present. CONCLUSIONS: The
      clinicopathologic features of a treated eye with well-defined extrafoveal CNV,
      and the fellow eye with a disciform scar, both associated with ARMD, are
      presented. Although laser treatment obliterated a choroidal neovascular membrane,
      11 additional areas of early, subclinical CNV were present.

PMID- 9654417
TI  - Three-dimensional ophthalmic contact B-scan ultrasonography of the posterior
      segment.
AB  - PURPOSE: A system to produce three-dimensional computer reconstructions of
      ophthalmic contact B-scan ultrasound was developed and investigated. METHODS:
      Investigators used ocular phantoms to measure the accuracy and reproducibility of
      linear, area, and volume measurements. RESULTS: In vitro calibration tests of
      linear and area measurements demonstrate accurate and reproducible findings
      throughout the imaged space. Phantom volume tests also show reasonable accuracy
      and reproducibility. CONCLUSIONS: Three-dimensional ultrasonography is effective
      in measuring length, area, and volume in an experimental model. The in vitro
      accuracy and reproducibility of measurements warrants further investigation into
      the clinical utility of this method in posterior segment tumors and other
      posterior segment pathology.

PMID- 9654418
TI  - Inhibition of postvitrectomy fibrin using troxerutin.
AB  - PURPOSE: To evaluate the efficacy of intraocular infusion of troxerutin in the
      inhibition of fibrin formation after vitrectomy in a rabbit model. METHODS:
      Lensectomies and vitrectomies were performed in a masked fashion on seven eyes
      treated with a 10-mM infusion of troxerutin and on seven control eyes that
      received only a balanced salt solution infusion. Masked grading of intraocular
      fibrin formation and intravitreal hemorrhage was performed for 1 week. RESULTS:
      On postoperative days 1 and 2, the control group exhibited a greater mean fibrin
      index (MFI) percentage than the troxerutin-treated group (day 1, 27.7% versus
      19.5% MFI; day 2, 14.5% versus 6.1% MFI, respectively). On postoperative day 3,
      both groups showed an MFI of 1.8%. On postoperative days 5 and 7, both groups
      showed only minimal presence of fibrin. Neither of the two groups had an
      increased rate of intraocular hemorrhage. CONCLUSIONS: Infusion of 10 mM
      troxerutin resulted in a relative decrease in the amount of fibrin produced
      without an increased risk of intraocular hemorrhage in treated eyes compared with
      controls, but the difference was not statistically significant. Further studies
      may be warranted to evaluate the optimal dose of troxerutin alone or a possible
      role for its use in conjunction with other drugs employing a different mechanism
      of action in the prevention of fibrin formation.

PMID- 9654419
TI  - Disparity between fundus camera and scanning laser ophthalmoscope indocyanine
      green imaging of retinal pigment epithelium detachments.
AB  - PURPOSE: Indocyanine green (ICG) angiograms of each of five patients with retinal
      pigment epithelium (RPE) detachments were made using first a Topcon fundus camera
      and then a Heidelberg scanning laser ophthalmoscope (SLO); for each patient, both
      types of angiograms were obtained on the same day. In each case, the serous fluid
      appeared bright throughout the fundus camera studies and dark throughout the SLO
      studies. This study sought to explain the disparity in the appearance of the
      lesions in the two kinds of images and to determine whether there was dye in the
      serous fluid. METHODS: Simple model eyes were constructed to demonstrate the
      effects of Mie light scatter and integrating sphere behavior of the sclera on ICG
      image formation by the fundus camera and SLO optics. Analysis was made of both
      the clinical angiograms and model eye images to structure an explanation for the
      disparate RPE detachment angiographic images. RESULTS: Indocyanine green
      fluorescent light from choroidal vessels adjacent to the lesions and scattered by
      the turbid serous fluid accounted for the lesion brightness seen in the fundus
      camera images. The models confirmed that SLOs suppress scattered light.
      CONCLUSIONS: The apparent fluorescence of serous fluid beneath RPE detachments in
      fundus camera early-phase ICG angiogram images is not attributable to the
      presence of dye; rather, it appears to be attributable to serous fluid light
      scatter of fluorescent light arising from adjacent fluorescent structures. This
      light scatter is a consequence of the fundus camera illumination and recording
      optics and is not present in SLO-generated images. The necessity of understanding
      such phenomena as absorption, diffraction, polarization, and scatter of light and
      routinely applying them to ICG angiogram interpretation is underscored when it is
      shown that they offer simple explanations for unusual or unexpected angiographic
      results, as in the case of the patients with RPE detachment discussed here.

PMID- 9654420
TI  - Diagnostic and therapeutic challenges.

PMID- 9654421
TI  - Recurrent cryptococcal choroiditis in a renal transplant patient:
      clinicopathologic study.

PMID- 9654422
TI  - Leber's neuroretinitis in a patient with serologic evidence of Bartonella
      elizabethae.

PMID- 9654423
TI  - Management of suspected endophthalmitis in vitrectomized, gas-filled eyes.

PMID- 9654424
TI  - Bilateral endogenous Candida endophthalmitis.

PMID- 9654425
TI  - Sulfur hexafluoride does not escape from plastic syringes capped with fine
      needles.

PMID- 9654426
TI  - Autogenous fascia lata leg grafts for exposed scleral buckles.

PMID- 9654427
TI  - Lung carcinoma metastatic to the vitreous cavity.

PMID- 9654428
TI  - Definition of macular hole surgery end points: elevated/open, flat/open,
      flat/closed.

PMID- 9654429
TI  - Severe ocular trauma managed with primary pars plana vitrectomy and silicone oil.

PMID- 9654430
TI  - Verb retrieval and sentence production in aphasia.
AB  - This paper presents a subject with a selective verb retrieval deficit. Nouns were
      produced more successfully than verbs in spontaneous speech, picture naming and
      when naming to definition. The word class effect was not observed in
      comprehension tasks, reading aloud or writing. This indicated that it was due to
      a specific problem in accessing verbs' phonological representations from
      semantics. The second part of the paper explores the implications of the verb
      deficit for sentence production. Analyses of narrative speech revealed a
      typically agrammatic profile, with minimal verb argument structure and few
      function words and inflections. Two investigations suggested that the sentence
      deficit was at least partly contingent upon the verb deficit. In the first, the
      subject was asked to produce a sentence with the aid of a provided noun or verb.
      The noun cues were not effective in eliciting sentences, whereas verb cues were.
      The second investigation explored the effects of therapy aiming to improve verb
      retrieval. This therapy resulted in better verb retrieval and improved sentence
      production with those verbs. These findings suggest that an inability to access
      verbs' phonological representations can severely impair sentence formulation.
      Implications for models of sentence production are considered.

PMID- 9654431
TI  - Sentence production by aphasic patients in a constrained task.
AB  - Sixty aphasic patients and 55 normal control subjects were tested on a sentence
      production protocol that required subjects to produce specific sentence types
      from semantic representations. Normal subjects produced the expected targets with
      great reliability. Analysis of the patients' performance indicated that patients
      had difficulty producing both grammatical forms and thematic roles. Patients had
      more trouble producing grammatical elements than content words, and showed
      differential difficulty on sentence types that had more grammatical elements and
      in which the order of thematic roles was non-canonical. The results provide
      evidence regarding the processing load imposed by different components of the
      sentence production process.

PMID- 9654432
TI  - Constraints on sentence priming in the cerebral hemispheres: effects of
      intervening words in sentences and lists.
AB  - This study explored the role of syntactic organization on semantic facilitation
      for target words presented to the right (R) and left (L) visual fields (VFs).
      Sentence and unstructured list primes were contrasted and, in each condition, the
      effect of intervening unrelated words on the durability of priming within each
      VF/hemisphere was investigated. Each prime contained a critical word which
      occurred Near (one intervening word) or Far (six intervening words) from the
      target word and was semantically related to it or a neutral control. It was
      hypothesized that, for word lists, facilitation for RVF target words would
      decrease with increasing distance between the critical and target words. For
      sentences no decrease in facilitation was expected for RVF targets. However, for
      LVF targets, facilitation was expected to decrease with distance both for
      sentences and lists with no greater priming for sentences than for lists. The
      results supported these hypotheses. Priming effects that spanned several
      intervening items were found only when the primes were well-structured, normal
      sentences and the target words were presented to the RVF. These results suggest
      that while word-level priming processes are available to both hemispheres, the
      left hemisphere makes greater use of message-level syntactic and semantic
      mechanisms for sentence comprehension.

PMID- 9654433
TI  - First-language acquisition in adolescence: evidence for a critical period for
      verbal language development.
AB  - It has been hypothesized that there is a critical period for first-language
      acquisition that extends into late childhood and possibly until puberty. The
      hypothesis is difficult to test directly because cases of linguistic deprivation
      during childhood are fortunately rare. We present here the case of E.M., a young
      man who has been profoundly deaf since birth and grew up in a rural area where he
      received no formal education and had no contact with the deaf community. At the
      age of 15, E.M. was fitted with hearing aids that corrected his hearing loss to
      35 dB, and he began to learn verbal Spanish. We describe his language development
      over the 4-year period since his acquisition of hearing aids and conclude that
      the demonstrates severe deficits in verbal comprehension and production that
      support the critical period hypothesis.

PMID- 9654434
TI  - Effects of unilateral spatial neglect on spatial agraphia of kana and kanji
      letters.
AB  - Left unilateral spatial neglect (USN) and spatial agraphia are both caused by
      right hemisphere damage. However, effects of USN on spatial agraphia have not
      been fully investigated. This study examined performances of patients with or
      without neglect and normals on single letter writing, using Japanese unique
      writing systems, kana (phonogram) and kanji (ideogram). Our patients exhibited
      agraphia of kanji, but not of kana. However, accuracy of writing was not
      associated to neglect severity, and errors for writing to dictation occurred
      either on the left or right side of kanji. Right frontal damage seemed to be
      related to the genesis of duplication or omission errors of repeated elements.
      Effect of USN was limited to spatial arrangement of letters and copying
      performance.

PMID- 9654435
TI  - Consonant and vowel production of right hemisphere patients.
AB  - Recent reports of subclinical phonetic deficits in posterior and most
      particularly in Wernicke's aphasics have challenged the traditional dichotomy
      which characterized speech deficits in aphasia as anterior/phonetic and
      posterior/phonological. It is unclear whether the basis of the phonetic deficit
      in posterior aphasics reflects the fact that the speech production system extends
      to more posterior regions of the left hemisphere than previously thought or
      alternatively is the result of generalized brain damage effects. The present
      study explores the latter possibility by investigating the patterns of speech
      production in right hemisphere brain-damaged, non-aphasic patients with anterior
      and posterior lesions. Acoustic analyses conducted on a range of consonant and
      vowel parameters showed differences between the speech patterns of both anterior
      and posterior right hemisphere patients and that of Wernicke's aphasics. These
      findings suggest that the subclinical deficit of Wernicke's aphasics can not
      simply be ascribed to a generalized brain-damage effect and raise the possibility
      that the right hemisphere also plays some role, if only a minor one, in the
      phonetic implementation of speech.

PMID- 9654437
TI  - Evidence for a global categorical representation of humans by young infants.
AB  - The representation of pictorial exemplars of humans by young infants was
      examined. Experiments 1B and 2 demonstrated an asymmetry with respect to the
      exclusivity of the categorical representations formed by 3- and 4-month-olds for
      humans and non-human animal species. The categorical representation for humans
      included novel humans, horses, cats, and fish, but excluded cars; the categorical
      representation for horses included novel horses, but excluded humans, fish, and
      cars. Experiment 2 also showed that the categorical representation for humans
      included exemplar information, whereas the categorical representation for non
      human animal species was based on summary information. The asymmetry in
      categorization of human versus non-human animal species did not extend to the
      presumed more basic process of discrimination of individual humans versus non
      human animals (Experiment 3). The findings suggest that a broad categorical
      representation of humans may be a cognitive reference point (or region) for young
      infants.

PMID- 9654438
TI  - Age changes in the missing-letter effect reflect the reader's growing ability to
      extract the structure from text.
AB  - Readers searching for a target letter in text are more likely to miss it in
      frequent function words than in less frequent content words, and the magnitude of
      this effect increases with age. While this increase has been taken to indicate
      that proficient readers process familiar words in terms of larger orthographic
      units, we propose that it reflects the reader's growing ability to extract the
      structure of text, resulting in a reduced emphasis on function than on content
      words. Indeed, comparing 2nd graders (7 to 7 1/2 years) and college students
      (Experiment 1) this increase was found even when function and content words were
      equated for frequency. Scrambling words within a sentence (Experiment 2) improved
      letter detection in function compared to content words among 7th graders (12 to
      13 years) and college students, but not among 3rd graders (8 to 9 years).
      Although letter detection was also affected by word frequency, the age
      differences noted above are possibly due not to the increasing familiarity of
      words, but rather to the growing sensitivity to their structural role in text.

PMID- 9654439
TI  - Implicit sequence learning in children.
AB  - The main purpose of the present study was to examine whether implicit learning
      abilities, assessed by means of a serial reaction time task, are present to the
      same extent in 6- and 10-year-old children as in adults. We also wondered whether
      the knowledge acquired after one learning session is retained after a 1-week
      delay. And finally, we studied the explicit knowledge developed by the children
      in this task. Our results show no age-related difference in the serial reaction
      time performance, which is consistent with the idea that implicit learning
      abilities may be efficient early in development.

PMID- 9654442
TI  - Are there non-trivial dynamic cross-correlations in proteins?
AB  - The analysis of internal motion in ensembles of flexible molecules in coordinate
      space requires the removal of overall motion by a least-squares fitting procedure
      of the Cartesian coordinates. It has been demonstrated that the choice of the
      atom set used for fitting influences the picture of the internal motion of BPTI.
      We have performed essential dynamics analyses of a 1 ns molecular dynamics
      trajectory of the single-stranded DNA-binding protein from the Pf3 phage using
      either all alpha-carbon atoms or the least mobile ones for fitting the trajectory
      prior to the analysis. We found that covariances of atoms separated by long
      distances were significantly reduced in the latter case; the overall overlap of
      essential spaces was still high. In the second part we present a method that does
      not introduce and bias caused by overall motion: principal component analysis in
      distance space. Non-trivial dynamic cross-correlations were preserved in distance
      space, which answers the question posed in the title in the affirmative. However,
      cross-correlations were throughout smaller than those detected by standard
      essential dynamics analyses.

PMID- 9654443
TI  - Crystal structure of a dominant B-cell epitope from the preS2 region of hepatitis
      B virus in the form of an inserted peptide segment in maltodextrin-binding
      protein.
AB  - We report here the crystal structure of MalE-B363, a recombinant construction of
      maltodextrin-binding protein bearing a dominant B-cell epitope sequence from the
      preS2 region of the hepatitis B surface antigen. The inserted peptide sequence,
      which replaces the seven carboxy-terminal residues of maltodextrin-binding
      protein, carries the 14 amino acid residue epitope contained between residues 132
      and 145 from the preS2 region. The epitope sequence is flanked on either side by
      additional residues that result from the genetically engineered insertion,
      bringing the total length of the foreign peptide to 26 amino acid residues. The
      hybrid protein has been previously shown to be recognised by monoclonal
      antibodies elicited by the native viral antigen. Three independent molecules of
      MalE-B363 are present in the asymmetric unit of the crystal. All 14 epitope
      residues could be traced for one molecule, ten epitope residues had significant
      electron density for the second, but no density was visible for the epitope of
      the third. The conformation of the amino-terminal segment of the epitope from
      Gln132(e) to Gly138(e) is similar in the two molecules of MalE-B363 for which the
      foreign peptide could be traced. Moreover, the conformation of a smaller segment,
      comprising residues Asp133(e) to Arg137(e), is similar to that present in the
      previously determined crystal structure of MalE-B133, another insertion/deletion
      mutant of maltodextrin-binding protein bearing the preS2 epitope. The presence of
      a common structural motif for the same sequence in disparate molecular
      environments suggests that this conformation might be present also in the native
      viral antigen. This could provide a structural basis to explain the cross
      reactivity of anti-preS2 monoclonal antibodies with these hybrid proteins.

PMID- 9654444
TI  - The mitochondrial processing peptidase behaves as a zinc-metallopeptidase.
AB  - The yeast mitochondrial processing peptidase (MPP) and its subunits were purified
      in Escherichia coli under conditions for which the enzyme retains most of its
      processing activity in the absence of externally added divalent cation. The
      holoenzyme exhibited a Km value of 1.35 microM and a Vmax value of 0.25
      microM/min and was inhibited by metal chelators in a time-dependent manner.
      Measurement of the metal content showed that both, MPP and beta-MPP, contained
      0.86 and 1.05 atoms of Zn2+ per molecule, respectively. An enzymatically inactive
      MPP mutant carrying a mutation of the first histidine of the putative metal-ion
      binding HXXEH motif in beta-MPP retained less than 0.2 atom of Zn2+ per molecule.
      A metal-free enzyme (apoenzyme) was prepared from the holoenzyme and shown to be
      devoid of any processing activity. Incubation of the apoenzyme with 50 nM and 500
      nM Zn2+ restored 50% and 80% of the processing activity, respectively. However,
      no reactivation occurred at concentrations of Zn2+ higher than 1 microM. Addition
      of 500 nM Mn2+ or higher concentrations (up to 50 microM) reactivated only 50% of
      the processing activity. The holoenzyme was competitively inhibited by molar
      excess of Zn2+ (Ki of 3.1 microM) but not by molar excess of Mn2+. Taken
      together, our data suggest that the authentic MPP is a Zn2+ rather than a Mn2+
      metallopeptidase.

PMID- 9654445
TI  - Pausing and termination by bacteriophage T7 RNA polymerase.
AB  - Two types of sites are known to cause pausing and/or termination by bacteriophage
      T7 RNA polymerase (RNAP). Termination at class I sites (typified by the signal
      found in the late region of T7 DNA, TPhi) involves the formation of a stable stem
      loop structure in the nascent RNA ahead of the point of termination, and results
      in termination near runs of U. Class II sites, typified by a signal first
      identified in the cloned human preproparathyroid hormone (PTH) gene, generate no
      evident structure in the RNA but contain a conserved sequence ahead of the point
      of termination, and also contain runs of U. Termination at class I and class II
      sites may involve non-equivalent mechanisms, as mutants of T7 RNA polymerase have
      been identified that fail to recognize class II sites yet continue to recognize
      class I sites. In this work, we have analyzed pausing and termination at several
      class II sites, and variants of them. We conclude that the 7 bp sequence ATCTGTT
      (5' to 3' in the non-template strand) causes transcribing T7 or T3 RNA polymerase
      to pause. Termination 6 to 8 bp past this sequence is favored by the presence of
      runs of U, perhaps because they destabilize an RNA:DNA hybrid. The effects of T7
      lysozyme on pausing and termination are consistent with the idea that termination
      involves a reversion of the polymerase from the elongation to the initiation
      conformation, and that lysozyme inhibits the return to the elongation
      conformation. A kinetic model of pausing and termination is presented that
      provides a consistent interpretation of our results.

PMID- 9654446
TI  - Possible roles of nucleocapsid protein of MoMuLV in the specificity of proviral
      DNA synthesis and in the genetic variability of the virus.
AB  - Retroviral nucleocapsid (NC) protein, in addition to its structural roles in the
      virion core, is involved in the early and late phases of the viral replication
      cycle. To further characterise the role of NC protein of MoMuLV (NCp10) in the
      replication of the viral genome, the influence of NCp10 on self-primed versus
      primer-specific reverse transcription has been analysed in vitro. The results
      show that NCp10 can enhance the specificity of proviral DNA synthesis by
      inhibiting self-primed cDNA synthesis while promoting primer-specific DNA
      synthesis within active NCp10-RNA nucleoprotein complexes. Retroviruses are known
      to show a high degree of variability and this prompted us to examine the possible
      implication of NCp10 in the genetic variability of MoMuLV. The ability of reverse
      transcriptase (RT) to extend different mutated primers using an RNA or a DNA
      template has been investigated in the presence or in the absence of NCp10. NCp10
      was found to have different effects on RT depending on the nature of the
      template: an enhancement at the elongation level of mutated primers using RNA as
      template versus a slight inhibition using DNA as template. These observations
      suggest that NCp10 could be implicated in the genetic variability of MoMuLV by
      allowing nucleotide misincorporation principally during minus strand DNA
      synthesis.

PMID- 9654447
TI  - A minisatellite "core" element constitutes a novel, chromatin-specific activator
      of mts1 gene transcription.
AB  - Expression of the mts1 gene is often associated with malignant transformation of
      tumor cells. Transcription of the gene is controlled by a number of positive and
      negative regulatory elements, all of them being localized in the first intron
      (+38 to +1215) of the mts1 gene. Through analysis of the distribution of DNase I
      hypersensitive sites in the first intron of the gene we revealed a structurally
      conserved region that consisted of a non-canonical NFkB binding site and a
      minisatellite "core" element. Deletion of the minisatellite core DNA in the
      context of the first intron had no effect on its regulatory capacity when assayed
      in transient transfections, while a fivefold decrease was observed in a pool of
      stably transfected cells. The minisatellite core sequence CTGGGCAGGCAG is
      involved in DNA-protein interactions in vivo, and is similar to a binding site
      for the previously identified minisatellite DNA sequence binding protein (Msbp
      1). The core DNA interacted in vitro with a protein that had an apparent
      molecular mass of 40 kDa. These data indicate that the minisatellite DNA
      represents the novel, chromatin-specific element in the mts1 complex enhancer.

PMID- 9654448
TI  - Cation-regulated self-association of "synapsable" DNA duplexes.
AB  - The simple innovation of introducing a block of G.G mismatches into a Watson
      Crick DNA duplex permits two such duplexes, under conditions of physiological
      temperature and salt, to "synapse" with one another at their G.G mismatch sites
      via guanine-quartet formation. The short quadruplex formed at the "synapsed" site
      necessarily has its strands in an antiparallel, or partially antiparallel
      orientation. We wished to test whether a different, and more stable, synapsis
      might be achieved if one of the two strands in the synapsable duplex had its
      domain of guanine residues in a reverse orientation to the rest of the strand,
      via 5'-5' and 3'-3' linkages. Such modified duplexes might synapse via the
      formation of the thermodynamically preferred parallel quadruplex. Our results
      indicate that such "parallel" and "antiparallel" synaptic events have
      dramatically different requirements for cations. We use chemical probing
      experiments to provide evidence for a kinetic model for this discrepancy. It may
      be possible to exploit the distinct properties of the above two kinds of
      synapsable duplexes for a variety of in vivo and in vitro applications.

PMID- 9654449
TI  - Formation of amyloid-like fibrils by self-association of a partially unfolded
      fibronectin type III module.
AB  - The ninth type III module of murine fibronectin was expressed in E. coli and
      folded into a compact homogeneous monomer whose unfolding and refolding were then
      investigated by fluorescence, circular dichroism, calorimetry and electron
      microscopy. The isolated module is unusually labile under physiological
      conditions. When heated at 1 deg. C/minute it exhibits an irreversible
      endothermic transition between 35 and 42 degrees C depending on the protein
      concentration. The transition is accompanied by changes in secondary and tertiary
      structure with partial exposure of the single tryptophan and increased binding of
      the hydrophobic probe, 1,8-anilinonaphthalene-sulfonate. The partially unfolded
      intermediate undergoes rapid self-association leading to the formation of large
      stable multimers that, like the original monomer, contain substantial amounts of
      beta sheet structure. The multimers melt and dissociate reversibly in a second
      endothermic transition between 60 and 90 degrees C also depending on the protein
      concentration. This second transition destroys the remaining secondary structure
      and further exposes the tryptophan. Visualization of negatively stained specimens
      in the electron microscope reveals that partially unfolded rmIII-9 slowly forms
      amyloid-like fibrils of approximately 10 nm width and indeterminate length. A
      subdomain swapping mechanism is proposed in which beta strands from one partially
      unfolded molecule interact with complementary regions of another to form
      oligomers and polymers. The possibility that similar interactions could play a
      role in the formation of fibrils by fibronectin in vivo is discussed.

PMID- 9654450
TI  - 1.8 A crystal structure of the major NAD(P)H:FMN oxidoreductase of a
      bioluminescent bacterium, Vibrio fischeri: overall structure, cofactor and
      substrate-analog binding, and comparison with related flavoproteins.
AB  - We have solved the crystal structure of FRase I, the major NAD(P)H:FMN
      oxidoreductase of Vibrio fischeri, by the multiple isomorphous replacement method
      (MIR) at 1.8 A resolution with the conventional R factor of 0.187. The crystal
      structure of FRase I complexed with its competitive inhibitor, dicoumarol, has
      also been solved at 2.2 A resolution with the conventional R factor of 0.161.
      FRase I is a homodimer, having one FMN cofactor per subunit, which is situated at
      the interface of two subunits. The overall fold can be divided into two domains;
      80% of the residues form a rigid core and the remaining, a small flexible domain.
      The overall core folding is similar to those of an NADPH-dependent flavin
      reductase of Vibrio harveyi (FRP) and the NADH oxidase of Thermus thermophilus
      (NOX) in spite of the very low identity in amino acid sequences (10% with FRP and
      21% with NOX). 56% of alpha-carbons of FRase I core residues could be superposed
      onto NOX counterparts with an r.m.s. distance of 1.2 A. The remaining residues
      have relatively high B-values and may be essential for defining the substrate
      specificity. Indeed, one of them, Phe124, was found to participate in the binding
      of dicoumarol through stacking to one of the rings of dicoumarol. Upon binding of
      dicoumarol, most of the exposed re-face of the FMN cofactor is buried, which is
      consistent with the ping pong bi bi catalytic mechanism.

PMID- 9654451
TI  - Structure determination of the small ubiquitin-related modifier SUMO-1.
AB  - The recently discovered small ubiquitin-related modifier SUMO-1 belongs to the
      growing family of ubiquitin-related proteins involved in postranslational protein
      modification. Unlike ubiquitin, SUMO-1 does not appear to target proteins for
      degradation but seems to be involved in the modulation of protein-protein
      interactions. Independent studies demonstrate an essential function of SUMO-1 in
      the regulation of nucleo-cytoplasmic transport, and suggest a role in cell-cycle
      regulation and apoptosis. Here, we present the first three-dimensional structure
      of SUMO-1 solved by NMR. Although having only 18% amino acid sequence identity
      with ubiquitin, the overall structure closely resembles that of ubiquitin,
      featuring the betabetaalphabetabetaalphabeta fold of the ubiquitin protein
      family. In addition, the position of the two C-terminal Gly residues required for
      isopeptide bond formation is conserved between ubiquitin and SUMO-1. The most
      prominent feature of SUMO-1 is a long and highly flexible N terminus, which
      protrudes from the core of the protein and which is absent in ubiquitin.
      Furthermore, ubiquitin Lys48, required to generate ubiquitin polymers, is
      substituted in SUMO-1 by Gln69 at the same position, which provides an
      explanation of why SUMO-1 has not been observed to form polymers. Moreover, the
      hydrophobic core of SUMO-1 and ubiquitin is maintained by conserved hydrophobic
      residues, whereas the overall charge topology of SUMO-1 and ubiquitin differs
      significantly, suggesting specific modifying enzymes and target proteins for both
      proteins.

PMID- 9654452
TI  - Engineering activity and stability of Thermotoga maritima glutamate
      dehydrogenase. I. Introduction of a six-residue ion-pair network in the hinge
      region.
AB  - Comparison of the recently determined three-dimensional structures of several
      glutamate dehydrogenases allowed for the identification of a five-residue ion
      pair network in the hinge region of Pyrococcus furiosus glutamate dehydrogenase
      (melting temperature 113 degrees C), that is not present in the homologous
      glutamate dehydrogenase from Thermotoga maritima (melting temperature 93 degrees
      C). In order to study the role of this ion-pair network, we introduced it into
      the T. maritima enzyme using a site-directed mutagenesis approach. The resulting
      T. maritima glutamate dehydrogenases N97D, G376 K and N97D/G376 K as well as the
      wild-type enzyme were overproduced in Escherichia coli and subsequently purified.
      Elucidation of the three-dimensional structure of the double mutant N97D/G376 K
      at 3.0 A, showed that the designed ion-pair interactions were indeed formed.
      Moreover, because of interactions with an additional charged residue, a six
      residue network is present in this double mutant. Melting temperatures of the
      mutant enzymes N97D, G376 K and N97D/G376 K, as determined by differential
      scanning calorimetry, did not differ significantly from that of the wild-type
      enzyme. Identical transition midpoints in guanidinium chloride-induced
      denaturation experiments were found for the wild-type and all mutant enzymes.
      Thermal inactivation at 85 degrees C occured more than twofold faster for all
      mutant enzymes than for the wild-type glutamate dehydrogenase. At temperatures of
      65 degrees C and higher, the wild-type and the three mutant enzymes showed
      identical specific activities. However, at 58 degrees C the specific activity of
      N97D/G376 K and G376 K was found to be significantly higher than that of the wild
      type and N97D enzymes. These results suggest that the engineered ion-pair
      interactions in the hinge region do not affect the stability towards temperature
      or guanidinium chloride-induced denaturation but rather affect the specific
      activity of the enzyme and the temperature at which it functions optimally.

PMID- 9654454
TI  - Editorial 
AB  - Copyright

PMID- 9654453
TI  - A common ancestor for oxygenic and anoxygenic photosynthetic systems: a
      comparison based on the structural model of photosystem I.
AB  - The 4 A structural model of photosystem I (PSI) has elucidated essential features
      of this protein complex. Inter alia, it demonstrates that the core proteins of
      PSI, PsaA and PsaB each consist of an N-terminal antenna-binding domain, and a C
      terminal reaction center (RC)-domain. A comparison of the RC-domain of PSI and
      the photosynthetic RC of purple bacteria (PbRC), reveals significantly analogous
      structures. This provides the structural support for the hypothesis that the two
      RC-types (I and II) share a common evolutionary origin. Apart from a similar set
      of constituent cofactors of the electron transfer system, the analogous features
      include a comparable cofactor arrangement and a corresponding secondary structure
      motif of the RC-cores. Despite these analogies, significant differences are
      evident, particularly as regards the distances between and the orientation of
      individual cofactors, and the length and orientation of alpha-helices. Inferred
      roles of conserved amino acids are discussed for PSI, photosystem II (PSII),
      photosystem C (PSC, green sulfur bacteria) and photosystem H (PSH,
      heliobacteria). Significant sequence homology between the N-terminal, antenna
      binding domains of the core proteins of type-I RCs, PsaA, PsaB, PscA and PshA (of
      PSI, PSC and PSH respectively) with the antenna-binding subunits CP43 and CP47 of
      PSII indicate that PSII has a modular structure comparable to that of PSI.

PMID- 9654455
TI  - Microwave applications in neuromorphology and neurochemistry: safety precautions
      and techniques.
AB  - In science, the introduction of a new method is never easy, not even if it
      concerns the use of a simple microwave oven. Most scientists do not realize the
      numerous applications of microwave techniques. This paper gives a broad overview
      of the application of microwave techniques in neuromorphology and neurochemistry,
      starting with a historical overview ranging from the introduction of microwave
      techniques as a scientific method in the 1970s to present. Organizations and
      publication rules are highlighted in the next part. The effect of microwave
      irradiation is discussed in two sections relating to microwave effects on the
      whole organism and on the neuron. The main body of the paper discusses the
      application of microwave techniques in the fields of neuromorphology and
      neuropathology. The paper then presents aspects of microwave irradiation as
      applied to ELISA techniques. In addition, cell fusion and cell reproduction under
      microwave irradiation are discussed.

PMID- 9654456
TI  - Problems and artifacts of microwave accelerated procedures in
      neurohistotechnology and resolutions.
AB  - Microwaving artifacts in histoprocessing and staining arise from the acceleration
      of diffusional and reactive processes. Because such accelerations provide the
      advantages of microwaving, and because microwave ovens cannot distinguish
      desirable from undesirable accelerations, artifacts are inevitable. Such
      microwaving problems can be categorized as follows: histoprocessing and staining
      reagents may be lost or altered; staining targets may move away from their in
      vivo sites, may be totally lost from the specimen, or may be altered; physical
      characteristics such as permeability of specimens or embedding resins may be
      changed; and staining processes themselves are sometimes different at elevated
      temperatures. The most general tips for detecting and/or avoiding such problems
      are to monitor and control the temperature of the reagents and the specimen, to
      standardize the procedures, and to observe the specimen and reagents carefully
      during microwaving when a new procedure is being introduced to the laboratory.

PMID- 9654457
TI  - Calibration and standardization of microwave ovens for fixation of brain and
      peripheral nerve tissue.
AB  - Rapid and reproducible fixation of brain and peripheral nerve tissue for light
      and electron microscopy studies can be done in a microwave oven. In this review
      we report a standardized nomenclature for diverse fixation techniques that use
      microwave heating: (1) microwave stabilization, (2) fast and ultrafast primary
      microwave-chemical fixation, (3) microwave irradiation followed by chemical
      fixation, (4) primary chemical fixation followed by microwave irradiation, and
      (5) microwave fixation used in various combinations with freeze fixation. All of
      these methods are well suited to fix brain tissue for light microscopy. Fast
      primary microwave-chemical fixation is best for immunoelectron microscopy
      studies. We also review how the physical characteristics of the microwave
      frequency and the dimensions of microwave oven cavities can compromise microwave
      fixation results. A microwave oven can be calibrated for fixation when the
      following parameters are standardized: irradiation time; water load volume,
      initial temperature, and placement within the oven; fixative composition, volume,
      and initial temperature; and specimen container shape and placement within the
      oven. Using two recently developed calibration tools, the neon bulb array and the
      agar-saline-Giemsa tissue phantom, we report a simple calibration protocol that
      identifies regions within a microwave oven for uniform microwave fixation.

PMID- 9654458
TI  - Microwaves and heat in aldehyde fixation: model experiments with bovine serum
      albumin.
AB  - Most model experiments concerning tissue fixation have used low concentrations of
      fixatives and proteins. Here, high concentrations (up to 32%) of bovine serum
      albumin (BSA) were reacted with formaldehyde (1-20%) and glutaraldehyde (0.5-4%).
      Gels were formed between 16% BSA and 10-20% formaldehyde at room temperature, but
      not with percentages of formaldehyde lower than 4%. Microwave application or
      heating in a water bath to 50 degrees C gave a gel from 1 to 20% formaldehyde.
      Sixteen percent BSA also gave a gel with glutaraldehyde from 0.5 to 4%. Cone and
      plate viscometry showed rapidly increasing viscosity at 4% formaldehyde and 16%
      BSA at room temperature. At 50 degrees C, gels formed at a low concentration of
      formaldehyde. Tissue fixation in which the local concentrations of protein may be
      in excess of 30% is probably more complete than in vitro experiments in which low
      concentrations of reagents have been used to permit subsequent spectrometry. This
      was confirmed by polyacrylamide gel electrophoresis of liver.

PMID- 9654459
TI  - Preservation and staining of myelinated nerve fibers.
AB  - Six procedures are given for preservation of myelinated nerve fibers for light or
      electron microscopic studies. These procedures fall into two main categories:
      those with and those without aldehyde fixation. Essentially different effects are
      attained by application of tannic acid, saline, microwave or conventional
      heating, or a decreased temperature. All procedures end in osmication. Three main
      aspects of myelinated fiber morphology are taken into account when judging the
      quality of their preservation: axon, myelin sheath, and axon/myelin coherence.
      Each aspect can be preserved excellently, but always in combination with a less
      superior quality of the other two aspects. Superior myelin quality is attained
      using microwave irradiation, either with aldehydes to which tannic acid is added
      or without aldehyde fixatives. Superior axon quality is attained with aldehydes
      and (conventional) heating. Axon/myelin coherence is best preserved by decreasing
      the temperature during the rinse with saline. Another two procedures provide
      good, though less superior, preservation of both axon and axon/myelin coherence.
      Next, the fixed tissue is embedded in plastic blocks from which semithin and
      ultrathin plastic sections are cut for light and electron microscopy,
      respectively. In addition to the standard procedure for toluidine blue staining
      on semithin sections, two microwave-supported procedures are described, which can
      be used as alternatives if the staining result is unsatisfactory. Furthermore, a
      toluidine blue staining procedure is described for glycol methacrylate (GMA)
      embedded material, which can be used if larger sections are needed.

PMID- 9654460
TI  - Antigen retrieval in formaldehyde-fixed human brain tissue.
AB  - Microwave-stimulated antigen retrieval has become a widely accepted method in
      both pathology and research laboratories. Since the introduction of the method in
      1991, many groups have tried to optimize and standardize it. This review
      describes the present state of the art. A standard method for microwave
      stimulated antigen retrieval in formaldehyde-fixed paraffin-embedded and
      nonembedded tissue is presented that results, in general, in very good staining
      for antibodies used in neuroscience. However, there are still a few antigens that
      are retrieved not at all or not in an optimal manner. Factors of importance for
      microwave antigen retrieval are the pH of the retrieval solution and, related to
      the pH, the temperature and duration of heating. These factors are discussed.

PMID- 9654461
TI  - Microwave-stimulated Jones-Marres method for staining fungi in brain tissue of
      immunocompromised patients.
AB  - Life-threatening fungal infections have increased significantly in the past
      decade due to the rising number of immunocompromised patients. Serological
      diagnosis of most fungal infections is unreliable and blood cultures are positive
      in only 50% of premortem cases; therefore, tissue sampling together with fast,
      reliable staining of fungi should be carried out to reach the correct, timely
      diagnosis. We developed, partly serendipitously, a microwave silver staining
      method for fungi in histological sections. During a differentiation step in
      periodic acid, background staining is removed. This rapid staining method can be
      combined with immunostaining, for example, the alpha smooth muscle actin method,
      to visualize blood vessels. Silver staining results were optimized using the
      recently developed MicroMED BASIC microwave labstation for histology (Milestone
      srl, Italy), featuring no-touch temperature measurements and PC control.

PMID- 9654462
TI  - Cell replication rates and processes concerning antibody production in vitro are
      not influenced by 2.45-GHz microwaves at physiologically normal temperatures.
AB  - Several contradictory papers concerning the effects of microwaves on living
      organisms and on in vitro cell suspensions have been published through the years.
      These papers are difficult to interpret, because temperature measurement data are
      often lacking. Reliable temperature measurements are important, because they
      enable one to determine whether the observed microwave effects are thermal or
      nonthermal. Therefore, a method was developed to investigate microwave effects on
      cellular processes, in which the temperature was precisely monitored during
      microwave treatment using a fiberoptic thermometer. This method involved the
      processes required for in vitro production of monoclonal antibodies. Monoclonal
      antibodies are vital ingredients in (microwave-stimulated) immunostaining
      techniques and ELISAs, which have become important techniques in neuroscience.
      The effects of 2.45-GHz microwaves on mouse myeloma and (neural) hybridoma cell
      replication rates and on antibody production were investigated. In addition, the
      effects on the cell fusion abilities of spleen lymphocytes and myeloma cells and
      on in vitro immunization were studied. The results of this study show no effects
      of microwaves on either of the processes mentioned using exposure times up to 5 h
      a day at a physiologically normal temperature of 37 degrees C. It was concluded
      that the effects of 2.45-GHz microwaves detected at higher temperatures are
      thermal effects and that no indications for nonthermal 2.45-GHz microwave effects
      exist under the exposure conditions used in the present study.

PMID- 9654463
TI  - EPR and DNP properties of certain novel single electron contrast agents intended
      for oximetric imaging.
AB  - Parameters of relevance to oximetry with Overhauser magnetic resonance imaging
      (OMRI) have been measured for three single electron contrast agents of the
      triphenylmethyl type. The single electron contrast agents are stable and water
      soluble. Magnetic resonance properties of the agents have been examined with
      electron paramagnetic resonance (EPR), nuclear magnetic resonance (NMR), and
      dynamic nuclear polarization (DNP) at 9.5 mT in water, isotonic saline, plasma,
      and blood at 23 and 37 degreesC. The relaxivities of the agents are about 0.2-0.4
      mM-1s-1 and the DNP enhancements extrapolate close to the dipolar limit. The
      agents have a single, narrow EPR line, which is analyzed as a Voigt function. The
      linewidth is measured as a function of the agent concentration and the oxygen
      concentration. The concentration broadenings are about 1-3 microT/mM and the
      Lorentzian linewidths at infinite dilution are less than 1 microT in water at
      room temperature. The longitudinal electron spin relaxation rate is calculated
      from the DNP enhancement curves. The oxygen broadening in water is about 50
      microT/mM O2 at 37 degreesC. These agents have good properties for oximetry with
      OMRI.

PMID- 9654464
TI  - Pulse sequences for steady-state saturation of flowing spins.
AB  - It is useful to be able to suppress the NMR signal from spins in a flowing fluid,
      for example for "black-blood" visualization of blood vessels in vivo, for the
      suppression of flow artifacts, and for the estimation of tissue perfusion by
      continuous labeling of inflowing arterial spins. This work considers the flow of
      fluid through a region in which it is subjected to a train of saturation pulses.
      Computer simulations and in vitro measurements show that a train of equal
      duration spoiler pulses produces less effective suppression than does a train of
      pulses of geometrically increasing duration. It is shown analytically that a long
      train of ideal equal-duration spoiler pulses converts initial magnetization (0,
      0, M0) into a combination of longitudinal and transverse magnetization equal to
      0. 29 (-M0, 0, M0) and is therefore unsatisfactory for continuous saturation.

PMID- 9654465
TI  - Temporal characteristics of NMR signals from spin 3/2 nuclei of incompletely
      disordered systems.
AB  - Anisotropic nuclear quadrupole interactions can produce residual quadrupole
      splitting in the NMR spectra of rapidly moving quadrupolar nuclei in incompletely
      disordered aqueous heterogeneous systems. Such systems may include hydrated
      sodium nuclei in biological tissue and biopolymer gels. To describe the NMR
      signals from such samples, we use a domain model in which each domain is
      characterized by a quadrupole frequency and a residence time of the nucleus. We
      show that the signals from each domain after one pulse, the quadrupole echo
      sequence, and the various multiple quantum filters (MQFs) can be expressed as a
      linear combination of five different phase coherences. To simulate the effect of
      various distributions (Pake powder pattern, Gaussian, etc.) of quadrupole
      frequencies for different domains on the NMR signal, we have written the computer
      program CORVUS. CORVUS also includes the effects of exchange between different
      domains using diffusion and random jump models. The results of computer
      simulations show that the Gaussian and Pake powder pattern quadrupole frequency
      distributions produce very different phase coherences and observable NMR signals
      when the exchange rate (1/taue) between different domains is slow. When 1/taue is
      similar to the root mean square quadrupole frequency (final sigma), the signals
      from the two distributions are similar. When 1/taue is an order of magnitude
      greater than final sigma, there is no apparent evidence of quadrupole splitting
      in the shape of the signal following one pulse, but the residual effects of the
      quadrupole splitting make a significant contribution to the fast transverse
      relaxation rate. Therefore, in this case, it is inappropriate to use the observed
      biexponential relaxation rates to obtain a single correlation time. The
      quadrupole echo and the various MQF signals contain an echo from the satellite
      transitions in the presence of quadrupole splitting. The peak of this echo is
      very sensitive to 1/taue. The time domain analysis of these signals is more
      direct and less ambiguous than the frequency domain analysis because the echo
      does not occur at the beginning of data acquisition. The quadrupole echo pulse
      sequence is the most sensitive detector of residual quadrupole splitting and
      exchange of sodium ions between different domains. However, if the sample is
      compartmentalized so that only a fraction of the nuclei have quadrupole
      splitting, the double quantum magic angle filter (DQ-MA) is more suitable. This
      is because the DQ-MA signal contains only the contributions from satellite
      transitions. Use of simulations to analyze signals from various one-pulse,
      quadrupole echo, and multiple quantum filter pulse sequences can yield
      information on substrate order and aid in quantitation of multiple quantum filter
      signals.

PMID- 9654466
TI  - Detection of proton chemical exchange between metabolites and water in biological
      tissues.
AB  - Metabolites in proton chemical exchange with water were detected via the water
      proton signal using saturation transfer techniques in model systems and
      biological tissues. The metabolites were selectively saturated and the resulting
      decrease in the much larger water proton pool was used to monitor the metabolite.
      This indirect detection scheme can result in a several orders of magnitude
      increase in sensitivity for metabolites over direct detection methods. A control
      irradiation scheme was devised to compensate for macromolecular/water
      magnetization transfer. Using this approach, significant chemical exchange
      regions at approximately 1 and 2.5 ppm were detected in kidney medulla. Using a
      difference imaging technique between a control irradiation above (-1.74 ppm) and
      below (+1.74 ppm) the water resonance, a chemical exchange image of the kidney
      was calculated. These data revealed a linear gradient of chemical exchange
      increasing from the cortex to the medulla. Studies on medullary acid extracts and
      urine revealed that the exchange observed in the kidney was predominantly with
      low molecular weight metabolites. Urea (1 ppm) was identified as contributing to
      the kidney/urine chemical exchange; however, other unidentified metabolites may
      also contribute to this effect. These studies demonstrate that tissue metabolites
      can be detected and imaged via the water protons using the signal amplification
      properties of saturation transfer in the presence of water/macromolecule
      magnetization transfer.

PMID- 9654467
TI  - Two-dimensional nuclear-Zeeman-resolved electron spin echo envelope modulation
      (NZ-ESEEM) spectroscopy.
AB  - A two-dimensional electron spin echo envelope modulation (ESEEM) experiment,
      called nuclear-Zeeman-resolved ESEEM (NZ-ESEEM), that correlates nuclear
      transition frequencies with nuclear Zeeman frequencies is introduced. NZ-ESEEM is
      basically a three-pulse ESEEM experiment complemented by a magnetic-field pulse
      applied during part of the free evolution period between the second and third
      microwave pulse. The inner working of the new approach is explained and the
      instrumentation is discussed. The capacity of the method is illustrated by two
      examples of applications.

PMID- 9654468
TI  - NMR temperature measurements using a paramagnetic lanthanide complex.
AB  - NMR thermometry has previously suffered from poor thermal resolution owing to the
      relatively weak dependence of chemical shift on temperature in diamagnetic
      molecules. In contrast, the shifts of nuclear spins near a paramagnetic center
      exhibit strong temperature dependencies. The chemical shifts of the thulium
      1,4,7, 10-tetraazacyclododecane-1,4,7,10-tetrakis(methylene phosphonate) complex
      (TmDOTP5-) have been studied as a function of temperature, pH, and Ca2+
      concentration over ranges which may be encountered in vivo. The results
      demonstrate that the 1H and 31P shifts in TmDOTP5- are highly sensitive to
      temperature and may be used for NMR thermometry with excellent accuracy and
      resolution. A new technique is also described which permits simultaneous
      measurements of temperature and pH changes from the shifts of multiple TmDOTP5-
      spectral lines.

PMID- 9654469
TI  - Resolution enhancement in multiple-quantum MAS NMR spectroscopy.
AB  - Two techniques for resolution and sensitivity enhancement are introduced in
      multiple-quantum (MQ) MAS spectroscopy of rigid solids. The first makes use of
      ultrafast MAS with spinning frequencies of up to 35 kHz, while the second
      combines MAS at moderately fast spinning frequencies of about 13 kHz with
      multiple-pulse (MP) dipolar decoupling. For the latter approach, a semiwindowless
      WHH-4 sequence is applied during the MQ evolution period (MQ dimension) and/or
      detection period (single-quantum dimension). In the MQ dimension, the MP sequence
      has to be supplemented by two bracketing pulses in order to preserve the order
      and the intensities of the evolving MQ coherences. Double-quantum 1H NMR spectra
      of l-alanine recorded using both decoupling techniques are shown and compared to
      each other. Triple-quantum 1H NMR spectra under ultrafast MAS conditions are also
      presented.

PMID- 9654470
TI  - Spectral editing technique for the in vitro and in vivo detection of taurine.
AB  - In vivo 1H NMR spectroscopy has proven to be a useful noninvasive tool for the
      investigation of numerous metabolic and physiological states. Taurine is
      potentially a useful indicator in neonate development and is involved in a number
      of physiological processes. However, it could not previously be observed in the
      in vivo 1H spectrum because of overlap with adjacent resonances. We have
      developed a spectral editing technique based upon double quantum filtration which
      allows the taurine resonances to be resolved from adjacent peaks. The experiment
      is demonstrated both on perchloric acid rodent brain extract and on rodent brain
      homogenate.

PMID- 9654471
TI  - Relaxation time determinations by progressive saturation EPR: effects of
      molecular motion and Zeeman modulation for spin labels.
AB  - The EPR spectra of nitroxide spin labels have been simulated as a function of
      microwave field, H1, taking into account both magnetic field modulation and
      molecular rotation. It is found that the saturation of the second integral, S, of
      the first harmonic in-phase absorption spectrum is approximated by that predicted
      for slow-passage conditions, that is, S approximately H1/1 + PH21, in all cases.
      This result is independent of the degree of inhomogeneous broadening. In general,
      the fitting parameter, P, depends not only on the T1 and T2 relaxation times, but
      also on the rate of molecular reorientation and on the modulation frequency.
      Calibrations for determining the relaxation times are established from the
      simulations. For a given modulation frequency and molecular reorientation rate,
      the parameter obtained by fitting the saturation curves is given by 1/P = a +
      1/gamma2eT1 . Teff2, where Teff2 is the effective T2. For molecular reorientation
      frequencies in the range 2 x 10(7)-2 x 10(8) s-1, Teff2 is dominated by the
      molecular dynamics and is only weakly dependent on the intrinsic T02, allowing a
      direct estimation of T1. For reorientation frequencies outside this range, the
      (T1T2) product may be determined from the calibrations. The method is applied to
      determining relaxation times for spin labels undergoing different rates of
      rotational reorientation in a variety of environments, including those of
      biological relevance, and is verified experimentally by the relaxation rate
      enhancements induced by paramagnetic ions.

PMID- 9654472
TI  - Investigating catalytic processes with parahydrogen: evolution of zero-quantum
      coherence in AA'X spin systems 
AB  - A systematic outline for the elucidation of the nature of hydrogenation
      intermediates with a lifetime too short to be directly detectable with standard
      NMR methods is presented. The method takes advantage of the special nature of the
      parahydrogen density operator and its inherent enhancement factor. The key aspect
      of these experiments is the evolution of zero-quantum coherence which is
      contained in the parahydrogen density operator. Analytical coherence transfer
      functions have been derived which describe the evolution of this zero-quantum
      coherence in spin systems consisting of three spins 1/2 that form an AA'X spin
      system. The analytical expressions presented form a basis for a thorough
      investigation of crucial catalytic steps. Copyright 1998 Academic Press.

PMID- 9654473
TI  - Lithium visibility in rat brain and muscle in vivo by 7Li NMR imaging.
AB  - The apparent concentration of lithium (Li) in vivo was determined for several
      regions in the brain and muscle of rats by 7Li NMR imaging at 4.7 T with
      inclusion of an external standard of known concentration and visibility. The
      average apparent concentrations were 10.1 mM for muscle, and 4.2-5.3 mM for
      various brain regions under the dosing conditions used. The results were compared
      to concentrations determined in vitro by high-resolution 7Li NMR spectroscopy of
      extracts of brain and muscle tissue from the same rats. The comparison provided
      estimates of the 7Li NMR visibility of the Li cation in each tissue region.
      Although there was considerable scatter of the calculated visibilities among the
      five rats studied, the results suggested essentially full visibility (96%) for Li
      in muscle, and somewhat reduced visibility (74-93%) in the various brain regions.

PMID- 9654474
TI  - Optimizing the 13C-14N REAPDOR NMR experiment: a theoretical and experimental
      study.
AB  - The optimum 14N pulse lengths in the 13C-14N rotational-echo adiabatic-passage
      double-resonance (REAPDOR) NMR experiment are determined from calculations and
      from experiments on samples of glycine and L-alanine. The REAPDOR experiment
      utilizes the adiabatic passages that 14N spins make between the 14N Zeeman energy
      levels during the application of a single, short 14N radiofrequency pulse. Use of
      a short 14N irradiation time of less than one-quarter of a rotor period ensures
      that the number of 14N spins that undergo more than one passage is minimized.
      This simplifies calculations describing 13C dipolar dephasing and provides better
      agreement between calculations and experiments. Recovery of the 13C-14N dipolar
      couplings and 14N quadrupolar coupling constants and asymmetry parameters is
      described.

PMID- 9654475
TI  - Monitoring local disposition kinetics of carboplatin in vivo after subcutaneous
      injection in rats by means of 195Pt NMR.
AB  - The anticancer drug carboplatin has been monitored in rats during treatment by
      means of in vivo 195Pt NMR spectroscopy at 2.0 T. The purpose of the study was to
      assess local disposition kinetics in intact tissue following subcutaneous
      injection of a platinum-containing drug. Serial 195Pt NMR measurements have been
      carried out in four animals after administration of carboplatin solutions with
      doses ranging from 37.1 to 59.4 mg per kg body weight. A surface coil of 2 cm
      diameter tuned to 18.3 MHz was placed over the injection site (back of the neck
      of the animals). To optimize measurement parameters of the single-pulse-acquire
      sequence and to determine chemical shifts and the detection threshold, in vitro
      195Pt NMR experiments have been performed on model solutions of potassium
      tetrachloroplatinate(II), carboplatin, and cisplatin with different solvents such
      as H2O, DMSO, and DMF. Resonances of PtCl2-4, carboplatin, cisplatin, and cis
      [Pt(NH2)Cl(DMSO)]+ were observed at chemical shift positions delta = -1623 ppm, 
      1705 ppm, -2060 ppm (cisplatin in DMSO), and -3120 ppm, respectively, relative to
      the reference signal of Na2PtCl6 at delta = 0 ppm. A spin-lattice relaxation time
      of carboplatin of T1 = (0.103 +/- 0.02) s was measured. The threshold for NMR
      detection of platinum-containing compounds estimated from the in vitro
      experiments was 10 micromol (corresponding to approximately 4.8 mM). In vivo
      195Pt NMR spectra obtained in four rats after administration of carboplatin
      showed a broad resonance at delta = -(1715 +/- 8) ppm. The signal-to-noise ratio
      of this peak (starting 2 min after the injection) was approximately 9:1 for a
      measurement time of 6 min (TR= 13 ms, 28672 transients). The elimination rate
      constant of local disposition of carboplatin was kel = 0.017 (0.008-0.025) min-1
      (median and range).

PMID- 9654476
TI  - Five-quantum coherence of I = 52 nuclei: 27Al in an Al2O3 single crystal 
AB  - Optimal conditions were calculated for excitation and detection of the five
      quantum coherence of quadrupolar nuclei with I = 52 in single crystals, observed
      by the two-pulse sequence (theta1)x - tau1 - (theta2)alpha - tau2, where alpha is
      the phase cycling angle. Variations in the pulse lengths, the relative values of
      the nutation frequency omega1 = gammaB1, and the quadrupolar frequency omegaQ as
      well as in the resonance offset were taken into account. In addition, the effect
      of the pulse length on the intensity of spectral lines was considered.
      Theoretical results were compared with experiments on 27Al nuclei in an Al2O3
      single crystal. Copyright 1998 Academic Press.

PMID- 9654477
TI  - Mapping molecular orientation in solids by rotating-frame NQR techniques 
AB  - A multi-dimensional NQR technique to image both the spatial distribution of
      quadrupolar nuclei and the local orientation of the electric field gradient
      tensor at the quadrupole sites in solids is reported. The encoding procedure is
      based on the irradiation of the sample by a pulse sequence composed of spatially
      homogeneous and inhomogeneous radiofrequency fields. A method that encodes the
      spatial and orientation information in the amplitudes of the free-induction decay
      signals and a proper three-dimensional reconstruction procedure that yields the
      space-orientation-dependent NQR spectra are described. A two-dimensional variant
      allows rapid measurement of the spatially dependent orientation distribution of
      molecules, disregarding the spectroscopic information. Copyright 1998 Academic
      Press.

PMID- 9654479
TI  - Earth's field NMR in antarctica: A pulsed gradient spin echo NMR study of
      restricted diffusion in sea Ice 
AB  - We report on the use in Antarctica of a nuclear magnetic resonance spectrometer
      which utilizes the terrestrial magnetic field. Free induction decay data are used
      to obtain estimates of brine content, in samples of sea ice extracted from the
      annual ice of McMurdo Sound, in the vicinity of Cape Evans, Ross Island. Pulsed
      gradient spin echo experiments were performed on these samples in which the
      orientation of the gradient with respect to the ice growth axis was varied and
      the separation time between the gradient pulses was varied. Anisotropic
      restricted diffusion effects are apparent and we use these to tentatively model
      the brine pocket morphology. Copyright 1998 Academic Press.

PMID- 9654478
TI  - An adiabatic multiple spin-echo pulse sequence: removal of systematic errors due
      to pulse imperfections and off-resonance effects.
AB  - Application of AFP (adiabatic fast passage) pulses for removal of systematic
      errors associated with multiple spin-echo sequences is demonstrated. The
      adiabatic fast passage pulses facilitate minimization of cumulative pulse errors
      for all three components of magnetization. It is also shown that off-resonance
      effects present in conventional CPMG sequences which degrade image quality in
      magnetic resonance imaging and introduce systematic errors in measured T2
      relaxation time peak amplitudes can be suppressed by introduction of AFP pulses
      without any degradation of overall signal intensity. The technique has been
      tested on the 15N spin-spin relaxation time measurements of a 110 amino acid
      domain of the F-actin cross-linking protein.

PMID- 9654480
TI  - Alignment echo of spin-3/2 9Be nuclei: detection of ultraslow motion 
AB  - It is demonstrated that the alignment echo of 9Be is quite useful for detecting
      ultraslow atomic motions in the metallic glass Zr46. 75Ti8.25Cu7.5Ni10Be27.5. The
      time scale of detectable atomic motion is between T2 = 1.5 ms and T1 of a few
      seconds. Similar to previous works of 2H NMR, the Jeener-Broekaert sequence is
      used to create quadrupolar order for spin-32 nuclei upon nonselective
      excitations. Since the chemical and Knight shift distributions are not negligible
      for 9Be, the proper choice of the dephasing time between the first and the second
      pulses is essential for achieving pure quadrupolar order. It is demonstrated
      experimentally that slow atomic motions contribute significantly to the decay of
      the alignment echo near the glass transition temperature. Copyright 1998 Academic
      Press.

PMID- 9654481
TI  - Simplification of 19F NMR spectra of liquid crystalline samples by multiple-pulse
      COSY experiments 
AB  - A general method is presented of converting second-order fluorine-19 spectra of
      liquid crystalline samples into first-order spectra. This is achieved by
      recording a 19F COSY spectrum with a multiple pulse dipolar reducing sequence
      (MPS) operating in the t1 period, leading to a F1 projection which is first
      order. The method is illustrated by recording spectra on a sample of 1,3-dichloro
      4-fluorobenzene dissolved in the nematic solvent ZLI 1167. Experiments have been
      done in which the MPS is either the MREV-8 or Flip-Flop-16 sequence. The first
      order F1 projections are analyzed to give reduced total 1H-19F couplings,
      KCSTHFij and the reduction factors, KCS, are obtained by comparison with the
      THFij available from an analysis of the ordinary 1D spectrum. The reduction
      factors are compared with values predicted by average Hamiltonian theory (AHT).
      The reasons for the differences found between observed and predicted values of
      KCS have been investigated by performing numerical simulations of the 2D MPS COSY
      experiments. Copyright 1998 Academic Press.

PMID- 9654482
TI  - In-phase double selective excitation of coupled spin systems using excitation
      sculpting 
AB  - An experiment that excites exclusively coupled nuclei pairsis presented. It
      involves the biselective defocusing and refocusing of coupled transverse
      magnetization under double pulsed field gradient spin echo conditions.
      Application to the extraction of subspectra from crowded COSY spectra is
      presented, as well as a doubly selective version of the homonuclear J-resolved
      experiment. Copyright 1998 Academic Press.

PMID- 9654483
TI  - High magnetic field gradient PGSE NMR in the presence of a large polarizing field
AB  - A description is given of pulsed gradient spin echo (PGSE) NMR experiments in
      which large pulsed magnetic field gradients may be required. The design
      contraints are discussed and, in particular, the problem of the use of large
      pulsed magnetic field gradients in conjunction with large polarizing fields is
      considered. Issues addressed concern probe mechanical assembly, current supply
      requirements, and pulse shape design. We describe a quadrupolar coil with a
      gradient amplitude of 1.65 T m-1 A-1 which has been used successfully up to a
      maximum gradient of around 40 T m-1. A diffusion coefficent of 7.5 x 10(-16) m2 s
      1 has been measured using this system, the lowest yet achieved by PGSE NMR
      methods. Copyright 1998 Academic Press.

PMID- 9654484
TI  - Coherence selection and excitation sculpting using RF-gradients in selective 1D
      experiments and nonselective 2D experiments 
AB  - The B0 gradient pulses can be replaced with long high-power pulses (RF-gradients)
      in z-rotation composite sandwiches. By doing this, practically all B0 gradient
      based pulse sequences can be performed with instruments lacking a field gradient
      accessory. We have implemented RF-gradients into selective 1D and nonselective 2D
      TOCSY and NOESY experiments. The spectral quality obtained with the RF-gradient
      method was comparable to that of the B0 method for small- to medium-sized
      molecules. There are also some advantages in using RF-gradients instead of B0
      gradients. There is practically no shift or coupling evolution during RF-gradient
      pulses. This may be significant in some experiments. Copyright 1998 Academic
      Press.

PMID- 9654485
TI  - A high-pressure, high-resolution NMR probe for experiments at 500 MHz.
AB  - A novel high-pressure, high-resolution NMR probe is described which operates at a
      frequency of 500 MHz. The design features an alternative RF coil (8 mm sample
      tube) for high frequency, sensitivity, probe power, and resolution (< 3.0 x 10(
      9)). The probe is capable of pressures to at least 5 kbar over a temperature
      range of -30 to 80 degreesC, and has a double-tuned 1H/2H circuit which can tune
      at 1H frequencies of either 300 or 500 MHz. The sensitivity of the 300-MHz
      circuit is over twice that of previous 10-mm high-pressure NMR probe designs,
      while at 500 MHz the sensitivity is nearly five times that of previous 300-MHz
      pressure probes. Potential biochemical applications are demonstrated by 2D NOESY
      spectra of a Troponin C mutant.

PMID- 9654486
TI  - A novel composite 90 degrees pulse sequence which provides distortionless NMR
      spectra and suppresses without destroying the water magnetization.
AB  - A novel 90 degrees composite pulse sequence which allows one to record 1D and 2D
      NMR spectra without disturbing the water magnetization is described. A home
      written program was used to optimize the pulse angles for which the pulse
      sequence response fitted best the desired excitation profile, producing a neat
      and distortionless spectrum with a broad null excitation at the carrier
      frequency. The resulting pulse sequence was first evaluated using the simulation
      program "PENCIL" and then tested on two protein samples. A 3.5 degrees phase
      shift of the last pulse was required to cancel correctly the water signal. The
      pulse scheme was appended to a NOESY pulse sequence. Inspection of the water
      cross section revealed interactions between water and some protons of
      drosomycine, a small insect antifungal protein.

PMID- 9654487
TI  - Fast broadband inversion by adiabatic pulses.
AB  - Despite the advantages of compensation for resonance offset and B1 inhomogeneity,
      adiabatic pulses are not yet in general use in high-resolution NMR, often because
      of the conception that these pulses require longer time or increased power to
      perform. We show that adiabatic pulses with tangential frequency sweeps and other
      frequency-modulation functions can be optimized to accomplish 13C and 1H
      broadband inversion using pulse lengths of 192 and 64 micro(s), respectively, at
      B1 strengths available with modern high-resolution probes.

PMID- 9654488
TI  - A simple one-dimensional solid-state NMR method to characterize the nuclear spin
      interaction tensors associated with the peptide bond.
AB  - We propose a simple one-dimensional RF pulse sequence for the study of chemical
      shift and heteronuclear dipolar coupling tensors of oriented as well as
      unoriented solids. An off-resonance RF decoupling of protons during the signal
      acquisition of less sensitive nuclei is used to suppress homonuclear 1H-1H
      dipolar interactions. This method is experimentally demonstrated on peptide
      samples selectively labeled with 15N isotope.

PMID- 9654489
TI  - Distributions of the quadrupolar and isotropic chemical shift interactions in two
      dimensional multiple-quantum MAS NMR spectra 
AB  - The distributions of both the quadrupolar and the isotopic chemical shift
      interactions are shown to give multiple-quantum MAS spectra that remain tilted
      after shearing. For both types of distribution, the theoretical slopes, formed by
      the resulting distribution of the centers of gravity of the signals, are
      calculated. Copyright 1998 Academic Press.

PMID- 9654490
TI  - Automated shimming with normal spectrometer hardware: 3D profile edge shimming 
AB  - A novel method is proposed for automated magnetic field homogeneity adjustment in
      high-resolution NMR. The method uses measurements of the edge frequencies of
      slice profiles recorded under static gradients to obtain three-dimensional
      magnetic field maps and does not require significant extra spectrometer hardware.
      Results are presented for the "cold" shimming of 5- and 10-mm-diameter probes in
      a 400-MHz narrow bore magnet. Copyright 1998 Academic Press.

PMID- 9654491
TI  - A robust method for determining the magnitude of the fully asymmetric alignment
      tensor of oriented macromolecules in the absence of structural information.
AB  - It has recently been shown that the degree of alignment of macromolecules in an
      aqueous dilute liquid crystalline medium of bicelles is sufficient to permit
      accurate values of residual 15N-1H, 13C-1H, and 13Calpha-C' dipolar couplings to
      be obtained on a routine basis, thereby providing potentially unique long-range
      structural information. To make use of this information in macromolecular
      structure determination, the magnitude of the axial and rhombic components of the
      molecular alignment tensor must be determined. This can be achieved by taking
      advantage of the fact that different, fixed-distance internuclear vector types
      are differently distributed relative to the alignment tensor. A histogram of the
      ensemble of normalized residual dipolar couplings for several such vector types
      approximates a powder pattern from which the magnitude of the axial and rhombic
      components are readily extracted in the absence of any prior structural
      information. The applicability of this method is demonstrated using synthetic
      data derived from four proteins representative of different sizes, topologies,
      and secondary structures, and experimental data measured on the small protein
      ubiquitin.

PMID- 9654492
TI  - Information from the water stripe in TOCSY experiments on systems with
      exchangeable protons.
AB  - The water "stripes" of the TOCSY maps of aqueous solutions of sucrose, of a 15
      aminoacid peptide, and of several of the constituent aminoacids are shown to
      contain correlations at the resonance frequencies of protons which are scalar
      coupled to OH or NH protons which exchange with the solvent. Theoretical analysis
      of chemical exchange during the spin-lock period in TOCSY elucidates the origin
      of these correlations, and shows that their intensities vary with the duration of
      the spin-lock period and with the exchange rate.

PMID- 9654493
TI  - RF microcoil design for practical NMR of mass-limited samples.
AB  - This paper addresses practical issues involved in obtaining high resolution 1H
      NMR spectra from samples containing less than 10 nmol. Solenoidal microcoils have
      been constructed to: (a) assess the effects of magnetic susceptibility mismatches
      at 500 MHz, (b) increase the concentration sensitivity of microcoil probes, (c)
      incorporate a lock channel for 2D experiments and long 1D acquisitions, and (d)
      assess the total amount of the sample required (with respect to the coil length)
      to avoid line broadening due to edge effects. Compared to previously published
      microcoil results, sample volumes have been increased by a factor of 20 with a
      concomitant decrease in the required concentration (5-20 mM). Perfluorocarbon
      susceptibility matching remained effective at 500 MHz, allowing acquisition of
      high resolution NMR spectra. A lock channel has also been successfully
      incorporated in microcoil probes. The limits of detection for sucrose with a 10
      min acquisition time were found to be 17.8 and 34.1 pmol for the single and
      double resonance coils, respectively. A sample length of approximately 10 times
      than that of the coil was required to avoid magnetic susceptibility artifacts.

PMID- 9654494
TI  - Detection of phosphomonoester signals in proton-decoupled 31P NMR spectra of the
      myocardium of patients with myocardial hypertrophy.
AB  - Proton-decoupled 31P NMR spectroscopy at 1.5 T of the anterior left ventricular
      myocardium was used to monitor myocardial phosphate metabolism in asymptomatic
      patients with hypertrophic cardiomyopathy (HCM, n = 14) and aortic stenosis (AS,
      n = 12). In addition to the well-known phosphorus signals a phosphomonoester
      (PME) signal was detected at about 6.9 ppm in 7 HCM and 2 AS patients. This
      signal was not observed in the spectra of normal controls (n = 11). We suggest
      that in spectra of patients with myocardial hypertrophy the presence of a PME
      signal reflects alterations in myocardial glucose metabolism.

PMID- 9654496
TI  - Meetings calendar 
AB  - Copyright

PMID- 9654495
TI  - Measurement of carbon-phosphorus J coupling constants in RNA using spin-echo
      difference constant-time HCCH-COSY.
AB  - We report a novel NMR technique for the measurement of carbon-phosphorus coupling
      constants in RNA oligomers. This method, spin-echo difference constant-time HCCH
      COSY, takes advantage of the well-dispersed H1' and C1' resonances to analyze
      couplings involving the more poorly dispersed ribose carbon and phosphorus
      resonances. The technique was applied to analysis of the 3JC2'P coupling
      constants related to backbone epsilon torsion angles in a 30-nucleotide lead
      dependent ribozyme. 3JC2'P coupling constants were obtained for approximately 90%
      of the residues in this RNA, which is over twice as many as could be obtained
      with previous methods.

PMID- 9654535
TI  - A one-year trial of lamivudine for chronic hepatitis B. Asia Hepatitis Lamivudine
      Study Group.
AB  - BACKGROUND AND METHODS: In preliminary trials, lamivudine, an oral nucleoside
      analogue, has shown promise for the treatment of chronic hepatitis B. We
      conducted a one-year, double-blind trial of lamivudine in 358 Chinese patients
      with chronic hepatitis B. The patients were randomly assigned to receive 25 mg of
      lamivudine (142 patients), 100 mg of lamivudine (143), or placebo (73) orally
      once daily. The patients underwent liver biopsies before entering the study and
      after completing the assigned treatment regimen. The primary end point was a
      reduction of at least two points in the Knodell necroinflammatory score. RESULTS:
      Hepatic necroinflammatory activity improved by two points or more in 56 percent
      of the patients receiving 100 mg of lamivudine, 49 percent of those receiving 25
      mg of lamivudine, and 25 percent of those receiving placebo (P<0.001 and P=0.001,
      respectively, for the comparisons of lamivudine treatment with placebo).
      Necroinflammatory activity worsened in 7 percent of the patients receiving 100 mg
      of lamivudine, 8 percent of those receiving 25 mg, and 26 percent of those
      receiving placebo. The 100-mg dose of lamivudine was associated with a reduced
      progression of fibrosis (P=0.01 for the comparison with placebo) and with the
      highest rate of hepatitis B e antigen (HBeAg) seroconversion (loss of HBeAg,
      development of antibody to HBeAg, and undetectable HBV DNA) (16 percent), the
      greatest suppression of HBV DNA (98 percent reduction at week 52 as compared with
      the base-line value), and the highest rate of sustained normalization of alanine
      aminotransferase levels (72 percent). Ninety-six percent of the patients
      completed the study. The incidence of adverse events was similar in all groups,
      and there were few serious events. CONCLUSIONS: In a one-year study, lamivudine
      was associated with substantial histologic improvement in many patients with
      chronic hepatitis B. A daily dose of 100 mg was more effective than a daily dose
      of 25 mg.

PMID- 9654536
TI  - Reversal of lesions of diabetic nephropathy after pancreas transplantation.
AB  - BACKGROUND: In patients with type I diabetes mellitus who do not have uremia and
      have not received a kidney transplant, pancreas transplantation does not
      ameliorate established lesions of diabetic nephropathy within five years after
      transplantation, but the effects of longer periods of normoglycemia are unknown.
      METHODS: We studied kidney function and performed renal biopsies before pancreas
      transplantation and 5 and 10 years thereafter in eight patients with type I
      diabetes but without uremia who had mild to advanced lesions of diabetic
      nephropathy at the time of transplantation. The biopsy samples were analyzed
      morphometrically. RESULTS: All patients had persistently normal glycosylated
      hemoglobin values after transplantation. The median urinary albumin excretion
      rate was 103 mg per day before transplantation, 30 mg per day 5 years after
      transplantation, and 20 mg per day 10 years after transplantation (P=0.07 for the
      comparison of values at base line and at 5 years; P=0.11 for the comparison
      between base line and 10 years). The mean (+/-SD) creatinine clearance rate
      declined from 108+/-20 ml per minute per 1.73 m2 of body-surface area at base
      line to 74+/-16 ml per minute per 1.73 m2 at 5 years (P<0.001) and 74+/-14 ml per
      minute per 1.73 m2 at 10 years (P<0.001). The thickness of the glomerular and
      tubular basement membranes was similar at 5 years (570+/-64 and 928+/-173 nm,
      respectively) and at base line (594+/-81 and 911+/-133 nm, respectively) but had
      decreased by 10 years (to 404+/-38 and 690+/-111 nm, respectively; P<0.001 and
      P=0.004 for the comparisons with the base-line values). The mesangial fractional
      volume (the proportion of the glomerulus occupied by the mesangium) increased
      from base line (0.33+/-0.07) to 5 years (0.39+/-0.10, P=0.02) but had decreased
      at 10 years (0.27+/-0.02, P=0.05 for the comparison with the baseline value and
      P=0.006 for the comparison with the value at 5 years), mostly because of a
      reduction in mesangial matrix. CONCLUSIONS: Pancreas transplantation can reverse
      the lesions of diabetic nephropathy, but reversal requires more than five years
      of normoglycemia.

PMID- 9654537
TI  - Lack of effect of walking on labor and delivery.
AB  - BACKGROUND AND METHODS: Walking during labor may reduce patients' discomfort and
      improve outcomes. We conducted a randomized trial of walking during active labor
      to determine whether it altered the duration of labor or other maternal or fetal
      outcomes. Women with uncomplicated pregnancies between 36 and 41 weeks' gestation
      and in active labor were randomly assigned either to walking or to no walking
      (usual care). Pedometers were used to quantify walking, and the time spent
      walking was recorded. RESULTS: Of the 536 women assigned to the walking group,
      380 actually walked. Their mean (+/-SD) walking time was 56+/-46 minutes. There
      were no significant differences between the women assigned to the walking group
      and the 531 women assigned to the usual-care group in the duration of the first
      stage of labor (6.1 hours in both groups, P=0.83), the need for labor
      augmentation with oxytocin (23 percent vs. 26 percent, P=0.25), and the use of
      analgesia (84 percent vs. 86 percent, P=0.59). Similarly, the percentages of
      women requiring delivery by forceps (4 percent vs. 3 percent, P=0.35) and
      cesarean section (4 percent vs. 6 percent, P=0.25) were not significantly
      different. These labor and delivery outcomes were unrelated to walking in both
      nulliparous and parous women. The infants' outcomes were also similar in the two
      study groups. CONCLUSIONS: Walking neither enhanced nor impaired active labor and
      was not harmful to the mothers or their infants.

PMID- 9654538
TI  - Enoxaparin plus compression stockings compared with compression stockings alone
      in the prevention of venous thromboembolism after elective neurosurgery.
AB  - BACKGROUND: Compression stockings are recommended for prophylaxis against venous
      thromboembolism in patients undergoing neurosurgery, but anticoagulant agents
      have not gained wide acceptance because of concern about intracranial bleeding.
      METHODS: In a multicenter, randomized, double-blind trial, we assessed the
      efficacy and safety of enoxaparin in conjunction with the use of compression
      stockings in the prevention of venous thromboembolism in patients undergoing
      elective neurosurgery. Enoxaparin (40 mg once daily) or placebo was given
      subcutaneously for not less than seven days beginning within 24 hours after the
      completion of surgery. The primary end point was symptomatic, objectively
      confirmed venous thromboembolism or deep-vein thrombosis assessed by bilateral
      venography, which was performed in all patients on day 8+/-1. Bleeding side
      effects were carefully assessed. RESULTS: Among the 307 patients assigned to
      treatment groups, 129 of the 154 patients receiving placebo (84 percent) and 130
      of the 153 patients receiving enoxaparin (85 percent) had venographic studies
      adequate for analysis. An additional patient in the placebo group died before
      venography of autopsy-confirmed pulmonary embolism. In this analysis, 42 patients
      given placebo (32 percent) and 22 patients given enoxaparin (17 percent) had deep
      vein thrombosis (relative risk in the enoxaparin group, 0.52; 95 percent
      confidence interval, 0.33 to 0.82; P=0.004). The rates of proximal deep-vein
      thrombosis were 13 percent in patients receiving placebo and 5 percent in
      patients receiving enoxaparin (relative risk in the enoxaparin group, 0.41; 95
      percent confidence interval, 0.17 to 0.95; P=0.04). Two patients in the placebo
      group died of autopsy-confirmed pulmonary embolism on days 9 and 16. Major
      bleeding occurred in four patients receiving placebo (intracranial bleeding in
      all four) and four patients (intracranial bleeding in three) receiving enoxaparin
      (3 percent of each group). CONCLUSIONS: Enoxaparin combined with compression
      stockings is more effective than compression stockings alone for the prevention
      of venous thromboembolism after elective neurosurgery and does not cause
      excessive bleeding.

PMID- 9654539
TI  - Images in clinical medicine. Floating right atrial thrombus and massive pulmonary
      embolism.

PMID- 9654540
TI  - Shattuck lecture--medicine and the media.

PMID- 9654541
TI  - Pulmonary embolism.

PMID- 9654543
TI  - Treatment of chronic hepatitis B infection.

PMID- 9654544
TI  - Pancreas transplantation and diabetic complications.

PMID- 9654545
TI  - Managing labor--never walk alone.

PMID- 9654548
TI  - Evaluation of the international academic activities of members of the japanese
      orthopaedic association 

PMID- 9654547
TI  - Human cloning and the challenge of regulation.

PMID- 9654549
TI  - Factors influencing lumbar spine bone mineral density assessment by dual-energy X
      ray absorptiometry: comparison with lumbar spinal radiogram.
AB  - A study was conducted to determine the effect of radiographic findings of lumbar
      spinal changes upon bone mineral density measurements obtained by dual energy X
      ray absorptiometry (DXA). Four hundred subjects were chosen from among 1543
      community residents, aged 40-79 years. Study groups of 50 subjects each were
      selected by sex and 10-year age groups. This study investigated 390 of the 400
      subjects who agreed to the conduct of spine bone mineral density measurement and
      spinal radiography. Lumbar spine radiograms were examined for findings of
      osteophyte formation, facet joint osteoarthritis, vertebral fracture, and aortic
      calcification. The prevalence of osteophyte formation, facet joint
      osteoarthritis, vertebral fracture, and aortic calcification increased with age
      in both men and women. On multiple regression analysis, bone mineral density was
      significantly higher (P < 0.001) in subjects with osteophyte formation or facet
      joint osteoarthritis than in those without these conditions, while bone mineral
      density was significantly lower in subjects with vertebral fracture. This study
      demonstrated that osteophyte formation, facet joint osteoarthritis, and vertebral
      fracture should be taken into account in the evaluation of bone mineral density
      by DXA in people in older age groups, since these conditions occur at a
      considerable rate in such subjects.

PMID- 9654550
TI  - Magnetic resonance imaging of anterior cruciate ligament (ACL) tears: diagnostic
      value of ACL-tibial plateau angle.
AB  - Tears of the anterior cruciate ligament (ACL) are often difficult to diagnose on
      magnetic resonance imaging (MRI), as it is often difficult to interpret the
      images. We developed a quantitative method for diagnosing ACL tears on MRI; the
      method involves measuring the angle formed by the intersection between a straight
      line drawn along the anterior border of the ACL and a straight line drawn along
      the medial tibial plateau (AT angle) on MRI. The AT angle was measured by two
      orthopedic surgeons approved by the Japanese Orthopedic Association and one
      orthopedic resident, none of whom had any prior knowledge of the physical and
      arthroscopic findings of the patients. Measurements were performed in 30 knees
      with ACL tears and 57 knees without tears. There was no significant difference
      between the AT angles measured by the three examiners in either the group with
      ACL tears or that without ACL tears. The mean value of the AT angle in the torn
      ACL group (33.9 +/- 1.1 degrees) was significantly smaller than that in the
      intact ACL group (52.3 +/- 1.0 degrees; mean +/- SE). When 45 degrees or less was
      set as the criterion defining a tear of the ACL, the diagnostic accuracy of our
      method was 87.4%; sensitivity was 93.3%, and specificity, 84.2%.

PMID- 9654551
TI  - Diagnosis of lumbar disc herniation by three-dimensional MRI.
AB  - The lumbo-sacral region has anatomical lordosis and two-dimensional magnetic
      resonance imaging (2D-MRI) cannot therefore show spinal roots including the
      dorsal root ganglions in one picture. This makes it difficult to present the
      lateral part of spinal root lesions. We have recently described a new three
      dimensional magnetic resonance imaging (3D-MRI) method which allows a
      stereoscopic view of the spinal cord and spinal nerve roots. In the present
      study, we evaluated three 3D-MRI techniques, rapid imaging spin echo (RISE) small
      tip angle gradient echo (STAGE), and short TI inversion recovery (STIR), for
      detecting disc tissue degeneration, and spinal cord and nerve root compression
      for identification of nerve roots and detecting signal changes indicative of
      thickening of the nerve root, and for evaluation of the extent of herniation in
      30 patients with lumbar disc herniation. The RISE method was superior for
      detecting signal changes in disc degeneration, (in 100% of patients) compared
      with the STAGE method (in 56.1% of patients). All methods poorly identified L4
      roots compared with L5 or S1 roots. The STIR method was the best for identifying
      nerve roots (L4, 62.5%; L5, 87. 5%; S1, 91.7%). STAGE and STIR were useful for
      detecting injuries of the nerve roots. RISE showed disc extrusion better than the
      other techniques (in 64.7% of patients). The presurgical diagnosis on 3D-MRI
      agreed with the pathology findings at surgery in 71.4% of STIR, 55.6% of RISE,
      and 33.3% of STAGE MR images. Our results indicate that 3D-MRI is most useful for
      the diagnosis of lumbar disc herniation and spinal cord and nerve root
      compression. The STIR method is best for identifying abnormalities of the spinal
      cord, roots, and intervertebral discs.

PMID- 9654552
TI  - Possible complications of magnetic coil stimulation in living tissue: assessment
      of changes in epiphyseal cartilage.
AB  - To assess the influence of repeated magnetic coil stimulation (MCS) of the
      peripheral nervous system on epiphyseal cartilage, we evaluated histological and
      structural changes after repeated MCS applied to the knee joints of young
      rabbits. There was a slight but significant histological change when repeated MCS
      at 100% intensity (100% of the maximal output) exceeded 600 times per day.
      However, we found no gross structural effects on the bone. We conclude that, if
      these results can be extrapolated to humans, MCS should be safe for stimulating
      peripheral nervous system for clinical electrophysiologic examinations in
      children.

PMID- 9654553
TI  - Influence of water immersion stress on peripheral nerve recovery in the rat.
AB  - An experimental study was performed to investigate the relationship between
      stress and peripheral nerve recovery. Male Wistar rats weighing 200-250 g were
      used. The sciatic nerve was crushed unilaterally with an aneurysm clip. Stress
      was applied by water immersion for 3 h, three times a week, from 1 week
      preoperatively, and continued for 6 or 8 weeks. The animals' walking tracks were
      measured every week to evaluate nerve function, and a sciatic functional index
      (SFI) was calculated. Specimens for histological examination were taken from the
      nerve at a site distal to the crush injury. By 3 weeks postoperatively, the SFI
      in the non-stress groups had recovered, but it remained at significantly lower
      levels in the stress groups (P < 0.01). Histological studies showed that the
      recovery of nerve fibers was retarded and regenerating axons were smaller in the
      stress groups. Peripheral nerve recovery after crush injury was suppressed by
      water-immersion stress.

PMID- 9654554
TI  - Changes in the extracellular matrix on the surface of sintered bovine bone
      implanted in the femur of a rabbit: an immunohistochemical study.
AB  - The interface of implanted True Bone Ceramics (TBC; sintered bovine bone; Koken,
      Tokyo, Japan) was examined. In the primary experiment, TBC was implanted into the
      bone marrow of a rabbit's femur. The extracellular matrices (types I, II, and III
      collagens and fibronectin) of decalcified specimens collected 1-48 weeks
      postoperatively were immunohistochemically examined. Undecalcified sections
      collected 6 weeks postoperatively were used for line analyses of calcium and
      phosphorus, by a scanning electron microscope-electron probe microanalysis (SEM
      EPMA) method. In a secondary experiment, TBC was implanted into an osteochondral
      defect of a femoral condyle, harvested 1-12 weeks postoperatively, and
      decalcified to examine the extracellular matrices at the interface. In the bone
      marrow in the early phase, TBC had absorbed quantities of fibronectin. Immature
      bone (containing both types I and III collagens) in direct apposition to the
      ceramic surface had matured (containing type I collagen alone) in the TBC pores.
      SEM-EPMA revealed the continuity of high levels of calcium and phosphorus at the
      TBC-bone interface. In the secondary experiment, enchondral ossification or
      fibrous tissue formation was observed near the articular surface. However, in the
      subchondral layer, direct bone formation was observed in the TBC pores. It was
      concluded that TBC has excellent bioactivity for inducing maturation of new bone
      matrix on porous surfaces.

PMID- 9654555
TI  - Role of norepinephrine and excitatory amino acids in edema of the spinal cord
      after experimental compression injury in rats.
AB  - The role of norepinephrine and excitatory amino acids in edema of the spinal cord
      after an acute experimental compression injury was studied in rats. Control rats
      received the compression injury only. Intraspinal norepinephrine was depleted in
      one rat group by injection of 6-hydroxydopamine (6-OHDA) into the subarachnoid
      space to selectively destroy catecholamine neurons and in a third group MK-801
      was administered intravenously to block receptors for N-methyl-d-aspartate
      (NMDA), an excitatory amino acid. Recovery from motor paralysis and suppression
      of edema of the spinal cord were then compared in the three groups. Significant
      recovery from motor paralysis was found 12 h after injury in the 6-OHDA-treated
      rats, compared with the controls, and 24 h after injury in the MK-801-treated
      rats. Edema of the spinal cord was significantly suppressed for up to 24 h after
      injury in the 6-OHDA-treated rats. The MK-801-treated rats showed no significant
      suppression of the edema until 24 h after the spinal cord injury. It was
      concluded that norepinephrine is primarily involved in the formation of vasogenic
      edemas, which develop in the early stages after an injury, whereas excitatory
      amino acids affect the formation of cytotoxic edemas, which develop at a
      relatively later stage.

PMID- 9654556
TI  - Site of origin of spinal cerebrospinal fluid pulse wave.
AB  - : Since vascular pulsation in the cerebrospinal fluid causes the cerebrospinal
      fluid pulse wave (CSFPW), spinal CSFPW may serve as a monitor of spinal cord
      blood flow. However, there are two possible sources of spinal CSFPW: brain and
      spinal cord pulsation, and it is unclear for which region spinal CSFPW provides
      blood flow information. To resolve this question, we analyzed changes in CSFPW
      caused by occlusion of the large vessels in mongrel dogs. The thoracic and
      abdominal aorta (TA group, n = 13; AA, n = 6), bilateral internal carotid
      arteries (ICA, n = 7), and superior and inferior vena cava (SVC, n = 6; IVC, n =
      8) were occluded. The CSFPW was measured at the second cervical and sixth lumbar
      spine level. To eliminate the influence of hemodynamic changes caused by the
      occlusion, CSFPWs were decomposed into component frequencies, harmonic waves
      (HWs), and analyzed using the system analysis method. After occlusion, cervical
      CSFPW was decreased in groups ICA (change in the first HW, 38%; P < 0.05 by
      Wilcoxon signed-ranks test), TA (40%; P < 0.05), and SVC (53%; P < 0.05), while
      lumbar CSFPW was decreased in groups TA (71%; P < 0.01), AA (78%; P < 0.05), and
      IVC (48%; P < 0.05). These results show that spinal CSFPW provides information on
      the blood flow of a relatively localized region, and could be used to monitor
      spinal cord blood flow.

PMID- 9654557
TI  - Capillaries with fenestrations around regenerating muscle fibers in the soleus
      muscle of the dystrophic (dy) mouse.
AB  - To investigate the morphological changes in capillaries around regenerating
      muscle fibers in the dystrophic (dy) mouse, we examined capillaries in the soleus
      muscles of 30-day-old control and dy mice by electron microscopy. In the control
      mice, the intramuscular capillaries were continuous. In the dystrophic mice, the
      muscles contained degenerative muscle fibers and many small muscle fibers
      regenerating after necrosis; these fibers had centrally located nuclei. The
      capillaries in the dy mice were mostly continuous, but some had a narrow vascular
      lumen around regenerating muscle fibers, possibly indicating newly formed
      capillaries. Moreover, about 20% of the capillaries with a narrow vascular lumen
      had a small number (less than five) of fenestrae bridged by a single-layered
      diaphragm. These findings suggest that capillary networks around muscle fibers
      regenerating after necrosis are remodeled by newly formed capillaries, and some
      of these capillaries have fenestrae in the endothelium to increase the supply of
      nutrients and oxygen to the regenerating muscle fibers.

PMID- 9654558
TI  - Treatment of brachial plexus injury.
AB  - A brachial plexus injury is the most severe nerve injury of the extremities. To
      achieve good results from treatment, correct diagnosis and early nerve repair are
      mandatory. The brachial plexus should be explored as early as possible if there
      is an incised wound, if clinical findings or diagnostic imaging indicate that at
      least one root is avulsed, if there is damage to the subclavian artery, and if
      there is total-type injury. With an upper-type injury with no clinical signs of a
      preganglionic lesion, the patient should be treated conservatively for 3 months
      and if there are no signs of recovery, then the brachial plexus should be
      explored. During this exploration, recording of the spinal cord evoked potential
      (ESCP) or the somatosensory evoked potential (SEP) is mandatory to determine the
      site of injury. Nerve grafting is indicated for a rupture in the root
      demonstrating a positive ESCP or SEP potential, in the trunk or in the cord.
      Exploration of the brachial plexus should be extended distally as far as possible
      to achieve good results after nerve grafting; when this was done more than M3
      (MRC grading) power of the infraspinatus, deltoid, and biceps was achieved in
      more than 70% of our 32, 30, 33 patients, respectively. Results of nerve grafting
      for the forearm muscles have been very poor. Intercostal nerve transfer is
      recommended to restore elbow flexion in root avulsion type of injury, with elbow
      flexion to more than M3 being regained in 70% of our 221 patients. The best
      results of intercostal nerve transfer were achieved in patients younger than 30
      years who received the operation within 6 months after injury. Motor recovery of
      hand function after intercostal nerve transfer was poor but protective sensation
      was restored in fingers innervated by the median nerve. The recommended treatment
      for each type of injury is described according to the results achieved.

PMID- 9654559
TI  - Management of tumor patients: introduction to the annual musculoskeletal tumor
      meeting of the japanese orthopaedic association 

PMID- 9654560
TI  - Axial alignment of the lower limb in patients with isolated meniscal tear.
AB  - Meniscal tears do not always result from trauma. To elucidate other factors
      responsible for meniscal tears, we evaluated the axial alignment of the lower
      limb in 385 patients (385 menisci) with isolated meniscal tear who were examined
      between 1972 and 1994. The patients were aged 50 years or less and had no
      ulceration or defect of articular cartilage of the knee when examined
      arthroscopically. Of the 385 menisci, 90 were lateral complete discoid; 110,
      lateral incomplete discoid; 68, lateral semilunar; and 117, medial semilunar.
      Patients in each of these four groups were divided into four subgroups according
      to sex and whether there was an obvious history of trauma. The so-called
      Mikulicz's mechanical axis of the affected side was utilized to evaluate the
      alignment. The axial alignment of the lower limb was normal in the patients with
      isolated tears of lateral complete discoid meniscus, lateral incomplete discoid,
      or lateral semilunar. It appeared that the axial alignment of the lower limb did
      not have a relationship with the occurrence of these tears. Patients with
      isolated tears of medial semilunar meniscus without obvious trauma, showed varus
      deformity of the knee. This deformity appeared to be closely related to the
      presence of medial meniscal tear.

PMID- 9654561
TI  - Age-related changes in cortical bone in women: metacarpal bone mass measurement
      study.
AB  - The mechanism of age-related cortical bone loss was investigated in 229 Japanese
      women, 41-94 years of age, by metacarpal bone mass measurement. While no
      significant correlation was found between bone width and age, a significant
      increase in bone marrow width, and significant decreases in cortical bone density
      and total bone mass were observed in association with aging (P < 0.0001). There
      was a significant negative correlation between total bone mass and bone marrow
      width (r = -0.239; P < 0.0005), and significant positive correlations between
      both total bone mass and cortical bone density (r = 0.539; P < 0.0001) and
      cortical bone width (r = 0.839; P < 0.0001). The findings suggested that age
      related cortical bone loss in middle-aged and elderly women resulted from two
      different factors; a decrease in cortical bone density caused by progression of
      intracortical porosity, and a decrease in cortical bone width as a result of bone
      loss on the endosteal surface. The latter had a greater influence on an age
      related cortical bone loss than the former.

PMID- 9654562
TI  - Detection of human serum antibody to encapsulated strains of Staphylococcus
      aureus by enzyme-linked immunosorbent assay inhibition test.
AB  - A specific and rapid enzyme-linked immunosorbent assay (ELISA) inhibition test
      was employed for detection of immunoglobulins to Staphylococcus aureus (S.
      aureus) capsular polysaccharide in human serum. Cap-sular polysaccharide antigens
      obtained from Smith diffuse (capsular type 2), Reynolds (capsular type 5), or
      Becker (capsular type 8) strains of S. aureus were added to microplates coated
      with these strains. Seventy-four patients with open fractures (31 serum samples
      from those with staphylococcal infections, 10 serum samples from those with non
      staphylococcal infections, and 33 serum samples from the non-infected group) and
      28 serum samples from healthy controls were then added. The plates were incubated
      at 37 degreesC for 2 h and the ELISA was performed. The ELISA inhibition assay
      showed remarkable inhibition with the capsular type 2, 5, and 8 polysaccharides
      in the 33 serum samples from the non-infected group and in the 28 serum samples
      from the healthy controls, but low inhibition was observed with the 31 sera with
      staphylococcal infections. Positive immunoglobulin (Ig)G and IgM titers showed
      marked inhibition with this assay, but IgA titer were not seen in any samples.
      These results indicate that the quantitation of human serum antibody against S.
      aureus capsular polysaccharide by the ELISA inhibition assay is useful for the
      demonstration of protective activities against S. aureus.

PMID- 9654563
TI  - Morphological study of mechanoreceptors on the coracoacromial ligament.
AB  - We performed gold chloride staining of coracoacromial ligaments removed at
      operation, observed the peripheral nerve endings in the ligament, and studied
      their distribution and changes with aging in order to clarify the proprioception
      of the shoulder joint. The coracoacromial ligament was found to contain four
      types of typical nerve endings: Pacinian corpuscles, Ruffini receptors, Golgi
      tendon organ-like receptors, and free nerve endings. In addition, non-typical
      Pacinian corpuscles and Ruffini receptors with non-typical morphology were
      present. There were also unclassifiable nerve endings with a morphology which did
      not fit any of the above categories. These typical, non-typical, and
      unclassifiable nerve endings were all widely distributed on the surface of the
      subacromial side at the insertion into the acromion and around the coracoid
      process in the ligament. Free nerve endings were found sporadically on the
      surface of the subacromial bursal side in the ligament. The resected
      coracoacromial ligaments (23 specimens) were divided into two groups based on the
      disorder that required surgery: a fracture group without subacromial impingement
      (5 specimens) and a group with subacromial impingement (18 specimens). Age
      related changes in the number of nerve endings were compared in each group. The
      total number of nerve endings decreased with age in both groups. The number of
      Pacinian corpuscles, Ruffini receptors, Golgi tendon organ-like receptors, and
      free nerve endings of typical morphology tended to decrease with age. The data
      from the fracture and subacromial impingement groups were not analyzed
      statistically because of the difference in the number of specimens in each group.
      However, the total number of nerve endings was lower in the subacromial
      impingement group than in the fracture group at all ages. The typical nerve
      endings of the coracoacromial ligament in both groups tended to decrease in the
      elderly, suggesting that the proprioception of the shoulder joint may become
      impaired with aging.

PMID- 9654564
TI  - Role of patellar tendon on the population of muscle fiber types and the
      contractile properties of single glycerinated muscle fibers in quadriceps muscles
      of rats.
AB  - The role of the patellar tendon (PT) in the contractile properties of quadriceps
      muscle was investigated. After PT resection (partial or complete), PT
      reconstruction, or a sham operation, rats were forced to run on a rodent
      treadmill. The histochemical and mechanical characteristics of the vastus
      medialis (VM) and vastus lateralis (VL) muscles were examined 2, 4, and 8 weeks
      after treatment. There were no significant changes in either fiber type
      population or the contractile properties of glycerinated single muscle fibers
      from VM and VL 2 and 4 weeks after partial PT resection. Complete PT resection
      caused a decrease in the population of type I fibers in VM, while the running
      training after PT reconstruction increased the population of type I fibers in VM.
      For both the PT resection and PT reconstruction groups, the Hill coefficient, an
      indicator of the Ca2+ sensitivity of myofilaments, was calculated from the pCa
      tension relationship of glycerinated single muscle fibers. In the PT
      reconstruction group, the Hill values for fibers isolated from VM were
      significantly decreased by running training, but the Hill values for VL were not.
      The effect of running training on the Ca2+ sensitivity of myofilaments in muscle
      fibers with PT reconstruction was different from that in muscle fibers without PT
      treatment. Both resection and partial resection of the PT in this animal model
      had heterogeneous effects on the contractile properties of quadriceps muscles; we
      presume that, clinically, we must give careful consideration to PT treatment.

PMID- 9654565
TI  - Tuberculous bursitis of the greater trochanter.
AB  - A patient with tuberculous bursitis of the greater trochanter is reported. A 37
      year-old woman had experienced persistent dull hip pain and noticed diffuse
      swelling over the greater trochanteric region. Plain radiograph revealed
      unremarkable osteopenic changes in the greater trochanter and faint
      mineralization in the vicinity of the trochanter. Computed tomogram showed
      erosion of the trochanter and a large soft tissue mass. Magnetic resonance
      imaging demonstrated a large multicystic mass. Histology of the cyst wall,
      showing chronic granulomatous tissue, and a positive culture of Mycobacterium
      tuberculosis confirmed the diagnosis of musculoskeletal tuberculosis. Complete
      excision of the lesion, followed by 6 months of antituberculous chemotherapy with
      rifampicin and isoniazid, cured the disease. There has been no sign of recurrent
      disease in 30 months of follow-up. Correct diagnosis was difficult because of its
      rarity, but modern imaging technology, magnetic resonance imaging, in particular,
      was extremely useful for showing the extent of the disease. Tuberculous infection
      should be considered as a differential diagnosis in patients with persistent hip
      pain.

PMID- 9654566
TI  - Normalization of the coronal and sagittal profile in idiopathic scoliosis:
      options of treatment.
AB  - There are many current strategies for normalizing coronal and sagittal profile in
      the idiopathic adolescent and adult scoliosis patient. Anterior and posterior
      approaches have their advantages and limitations. Many factors have to be
      considered in determining the "best" approach, as idiopathic scoliosis presents
      with a wide diversity of deformity and curve pattern. Those points are reviewed
      in this manuscript.

PMID- 9654567
TI  - Nasogastric and nasoenteric feeding tubes.
AB  - This article discusses the placement of nasogastric and nasoenteric feeding tubes
      using blind, pH, magnetic, sonagraphic, electromyogram, fluoroscopic, and
      endoscopic-assisted techniques. Bedside tests to ensure appropriate tube location
      are detailed. The complications of inappropriately-located tubes are listed, and
      methods to reduce adverse side effects are given.

PMID- 9654568
TI  - Percutaneous endoscopic gastrostomy.
AB  - Accessing the stomach via a gastrostomy is the preferred method for providing
      enteral nutritional support when supplementation is required for more than three
      or four weeks. Since its introduction in the early 1980s, percutaneous endoscopic
      gastrostomy has become the most popular method for creating a gastrostomy. It is
      a quick and cost-effective method and has supplanted open gastrostomy for the
      establishment of a gastrocutaneous fistula to provide access to the stomach for
      numerous indications. It is associated, however, with serious and potentially
      lethal complications which must be completely understood by the endoscopist. In
      addition, patient selection and thorough attention to details are paramount to
      the performance of a safe percutaneous endoscopic gastrostomy.

PMID- 9654569
TI  - Direct percutaneous endoscopic jejunostomy.
AB  - Jejunal feeding often is preferable to gastric feeding, particularly in the
      following situations: high risk for aspiration; gastric resection (partial or
      total); gastric pull-up; gastric outlet obstruction; obstructed or nonfunctioning
      gastrojejunostomy; and gastric dysmotility. The technique of placing a thin tube
      through a gastrostomy tube and pulling it endoscopically into the proximal
      jejunum allows delivery of nutrients into the jejunum. The results of this
      technique, however, have been poor. The direct percutaneous endoscopic
      jejunostomy technique allows placement of tubes directly in the jejunum with a
      success rate of around 85% and a minimal complication rate which is comparable to
      that of PEGs.

PMID- 9654570
TI  - Surgical and laparoscopic techniques for feeding tube placement.
AB  - Surgeons have at their disposal multiple options for providing enteral access in
      a myriad of circumstances. This article reviews the techniques for surgical
      placement of enteral access as well as the indications, benefits, and
      complications for each procedure. The feeding tubes commonly available are
      described, and considerations involved in the choice of procedure are discussed.

PMID- 9654571
TI  - Enteral feeding solutions.
AB  - There has been a widespread proliferation of enteral feeding solutions for
      general and specific therapeutic use. This article reviews the nutrient
      substrates and physical characteristics of these solutions with consideration to
      both psychological and clinically-proven principles pertinent to their
      application. The rationale for the composition and efficacy studies of disease
      specific solutions also is presented.

PMID- 9654572
TI  - Design and production of enteral feeding tubes.
AB  - The evolution of enteral feeding via tubes, syringes, and other mechanical
      devices probably began in Egypt before the birth of Christ. Today's feeding tubes
      are a safe and effective means for providing long-term feeding to patients unable
      to maintain sufficient nutrition by oral intake. The needs of enterally-fed
      patients are presently being met with feeding tubes that are biocompatible, easy
      to use, and relatively inexpensive to manufacture.

PMID- 9654573
TI  - Enteral feeding in critical care, gastrointestinal diseases, and cancer.
AB  - This article discusses the many advantages and changes that have occurred in the
      nutritional management of critically-ill patients, patients with gastrointestinal
      diseases, and patients with selected cancers. Mechanical obstruction is the only
      absolute contraindication to enteral nutrition. This article reviews the present
      aggressive approach to the use of enteral nutrition.

PMID- 9654574
TI  - Enteral nutritional support in burn patients.
AB  - Early and continued nutritional support has been determined to be an important
      component of therapy for seriously burned patients. The hypermetabolic response
      to severe injury requires increased calorie and protein intake to blunt the
      catabolism and loss of lean muscle mass. Enteral feeding has been found to
      directly nourish the gastrointestinal tract and may help reverse the defective
      gut barrier which accompanies burn shock. In contrast, intravenous nutritional
      support appears to lack effectiveness in burn patients and may actually increase
      morbidity and mortality.

PMID- 9654575
TI  - Enteral nutrition in the pediatric population.
AB  - Enteral feeding, the provision of liquid nutrients into the gastrointestinal
      tract, is an important component of pediatric care. For the infant or child with
      a functioning or even a partially-functioning GI tract, the use of the enteral
      route provides a safe and efficient means of delivering nutrition at a time of
      life when requirements are extremely high. In addition to high nutrient
      requirements in the early years of life, there are a number of specific pediatric
      conditions, such as failure to thrive, short bowel syndrome, and congenital heart
      disease, which place further demands on the growing child. These demands can be
      met through the careful use of enteral feeds. This article reviews the physiology
      and practical application of enteral feeding to the pediatric age group.

PMID- 9654576
TI  - Outcome of long-term enteral feeding.
AB  - In the past two decades, many technical advances have made tube enteral feeding
      much more comfortable and acceptable to patients and their families. This has
      greatly expanded the use of this therapy, both in clinical conditions where it
      was traditionally prescribed and in many other diagnoses. This expanded use
      raises important questions about how much enteral nutrition is being used, the
      medical outcome in different clinical conditions, and the quality of life
      experienced by long-term therapy users. This article addresses these outcome
      issues for patients in the nonhospital setting.

PMID- 9654577
TI  - Ethical issues in instituting and discontinuing enteral feeding.
AB  - The shift from inpatient care has not lessened the importance of ethical issues
      in caring for patients. Dilemmas involving withholding and withdrawing enteral
      nutrition require input from the patient, family, and caregivers. Decisions to
      forego or discontinue treatment such as home enteral support should never be
      distinguished from the responsibility of providing support and compassionate care
      throughout life, even during dying.

PMID- 9654578
TI  - Cost and cost-benefit of enteral nutrition.
AB  - Enteral nutrition is a therapy provided routinely in the hospital, extended care,
      and home care settings for patients who are unable to maintain adequate oral
      nutrition yet have a functioning gastrointestinal tract. Information about the
      cost and effectiveness or benefits of enteral nutrition in the hospital and home
      care settings is important to know when making decisions about providing this
      therapy. This article discusses the methods used in cost analysis, explains the
      difference between cost and charges, and reviews the current information known
      about the cost-effectiveness and cost-benefits of enteral nutrition in the acute
      care setting and at home.

PMID- 9654579
TI  - Techniques, coils, pulse sequences, and contrast enhancement in pediatric
      musculoskeletal MR imaging.
AB  - The first half of this article emphasizes the basic techniques involved in
      performing MR imaging of the pediatric musculoskeletal system. These include
      patient preparation, sedation issues, immobilization, coil selection, and pulse
      sequences. The second half of this article provides a detailed discussion of the
      use of Gadolinium and its enhancement characteristics in the normal developing
      musculoskeletal system, and its pathologic states are given.

PMID- 9654580
TI  - Growth cartilage: normal appearance, variants and abnormalities.
AB  - The cartilaginous structures in the growing ends of the bone have a complex
      anatomy. MR imaging allows exquisite depiction of these structures. The normal
      anatomy and biochemical features of the zones of cartilage are reviewed. Based on
      an analysis of signal characteristics, it is possible to optimize the use of
      pulse sequences to study the normal structures and abnormalities of growing bone.

PMID- 9654581
TI  - Normal bone marrow: signal characteristics and fatty conversion.
AB  - Understanding the dynamic MR appearance of normal bone marrow during childhood is
      essential. This article reviews normal bone marrow structure and development,
      especially the process of fatty conversion, laying the cornerstone for accurate
      interpretation of marrow MR imaging.

PMID- 9654582
TI  - Congenital anomalies and vascular birthmarks of the lower extremities.
AB  - MR imaging is an invaluable tool for the evaluation of congenital abnormalities
      and vascular birthmarks of the extremities in children. These abnormalities of
      the immature musculoskeletal system are often underestimated by radiography. MR
      imaging is useful for diagnosis, assisting in therapy, showing response to
      treatment, and determining prognosis. Localized and generalized abnormalities of
      the lower extremities and issues pertinent to their MR imaging are illustrated in
      this article.

PMID- 9654583
TI  - Musculoskeletal trauma in children.
AB  - MR imaging has facilitated the study of pediatric injuries by demonstrating the
      extraosseous and cartilaginous component of these lesions. In injuries to the
      epiphysis and physis, osteochondral injuries and avulsion injuries, the
      cartilaginous component is usually the most important part of the lesion. Stress
      fractures and other injuries to the marrow also can be demonstrated with MR
      imaging. In the context of musculoskeletal injuries in children, MR imaging is
      most valuable in demonstrating the extent of injuries to radiographically occult
      areas.

PMID- 9654584
TI  - MR imaging of pediatric musculoskeletal inflammatory and infectious disorders.
AB  - Inflammatory and infectious disorders of the skeletally immature extraspinal
      musculoskeletal system affect the bones, contiguous soft tissues, muscles, and
      joints. MR imaging of osteomyelitis, soft tissue infection, inflammatory muscle
      disease, and acute and chronic joint disease are discussed in the context of
      underlying pathophysiology. Discussion includes imaging optimization,
      contribution of MR imaging to overall patient management, and differential
      diagnostic considerations for the pediatric patient.

PMID- 9654585
TI  - Differential diagnosis of pediatric musculoskeletal masses.
AB  - MR imaging plays a major role in the evaluation of children with soft tissue and
      bone tumors. While the imaging characteristics of these lesions are often
      nonspecific, MR imaging provides valuable information on the extent of disease
      and relationship of tumors to the neurovascular bundle and other vital
      structures. This article reviews the radiographic and MR imaging appearances and
      clinical presentations of a wide range of musculoskeletal masses that occur in
      children.

PMID- 9654586
TI  - Advances in MR imaging of pediatric musculoskeletal neoplasms.
AB  - MR imaging has evolved as the most important diagnostic test for local staging of
      primary bone and soft tissue tumors, for monitoring response to chemotherapy, and
      for detecting postoperative tumor recurrence. MR imaging provides accurate
      preoperative staging of local tumor extent and helps to obtain adequate safety
      margins, prerequisites for successful limb-salvage surgery. Postcontrast MR
      imaging studies are helpful for evaluating the presence or absence of tumor
      necrosis during chemotherapy. Dynamic MR imaging after intravenous bolus
      administration of Gd-DTPA or other paramagnetic contrast media is particularly
      useful for assessing response to chemotherapy. Diffusion-weighted MR imaging is a
      new technique that is potentially capable of detecting and quantitating the
      amount of tumor necrosis after chemotherapy or radiation therapy.

PMID- 9654587
TI  - Diffuse marrow disorders in children.
AB  - This article describes MR imaging findings in neoplastic processes affecting the
      marrow of children. Differentiation from non-neoplastic processes, such as edema
      and hematopoietic marrow is described.

PMID- 9654588
TI  - Disorders of the Hip.
AB  - MR imaging has fulfilled many of the dreams of the pediatric radiologist studying
      the hip: it has allowed depiction of detailed anatomy, evaluation of vascularity
      and perfusion, determination of synovial proliferation activity in chronic
      arthritis, and detection of bone marrow changes with great sensitivity. MR
      imaging also has brought some disenchantments; it lacks specificity, it is
      expensive and long, and it often requires sedation. MR imaging is operator
      dependent and hardware and software dependent. Finally, issues of cost
      effectiveness and clinical efficacy in comparison with good physical examination
      and conventional radiography or ultrasound remain unresolved. Demonstration of
      its cost-effectiveness in the clinical setting is clearly the dominant challenge
      facing MR imaging today.

PMID- 9654589
TI  - The pediatric knee.
AB  - MR imaging has become an indispensable tool in the evaluation of knee disorders.
      It is now widely relied on by clinicians, especially orthopedic surgeons, for
      guiding arthroscopic procedures and for staging tumor prior to resection. MR
      imaging has proved so successful that it has largely replaced arthrography in the
      evaluation of knee problems.

PMID- 9654590
TI  - The pediatric foot and ankle.
AB  - MR imaging can be extremely helpful in evaluating congenital and acquired
      deformities of the foot and ankle. Knowledge of the normal developmental anatomy
      of the foot and ankle is important to accurately identify abnormalities versus
      normal variants. The foot and ankle may be abnormal because of trauma, infection,
      tumor, or systemic disease. MR imaging can help in the differential diagnosis of
      abnormalities as well as in treatment planning and follow-up.

PMID- 9654591
TI  - Disorders of the upper extremity in children.
AB  - This article presents a brief overview of the indications of MR imaging in a
      variety of disorders of the upper extremity of the pediatric patient. This covers
      congenital anomalies: Sprengel shoulder, Poland sequence, arthrogryposis;
      posttraumatic lesions of cartilage, bone, tendon, muscle and nerve including the
      brachial plexus injury; inflammatory arthritis and synovitis; bone and joint
      infection; osteochondritis dissecans, bone necrosis and infarcts in sickle cell
      anemia and juvenile Gaucher disease, as well as tumors. In this last category,
      the authors briefly describe the appearances of cysts and tumors of bones and
      soft tissues of the upper extremity. Indications for the intravenous
      administration of Gadolinium are given throughout the article with emphasis on
      the synovial enhancement seen in active arthritis and synovitis.

PMID- 9654592
TI  - Chemotherapy of oesophago-gastric cancer.
AB  - Oesophageal and gastric cancers are common tumors that represent a number of
      challenges for oncologists, gastroenterologists and surgeons. The prognosis
      remains poor with the majority of patients presenting with advanced disease.
      Combined chemotherapy and radiotherapy has demonstrated a survival benefit in
      patients with loco-regional oesophageal cancer compared to radiotherapy alone. In
      an interim analysis we have observed a 62% response rate using a chemoradiation
      regimen based on protracted venous infusion of 5-fluorouracil and cisplatin
      combined with radiotherapy in patients with inoperable oesophageal cancer.
      Improved outcomes with loco-regional disease has rekindled interest in
      preoperative therapy. In a trial comparing preoperative chemoradiation to surgery
      alone in patients with operable oesophageal adenocarcinoma, survival was improved
      with multimodality treatment. In addition, a study including both adeno- and
      squamous carcinomas demonstrated a trend towards improved survival. A complete
      pathological response to chemoradiation was associated with significantly
      improved survival. Gastric cancer is one of the most chemosensitive solid tumors
      of the gastrointestinal tract with the majority of patients being suitable for
      palliative chemotherapy. The ECF (epirubicin, cisplatin, protracted venous
      infusion 5-fluorouracil) regimen was developed in the Gastrointestinal unit of
      the Royal Marsden Hospital and first reported in 1991. In a prospective
      randomised trial including 274 patients ECF has been compared with the standard
      combination of 5-fluorouracil, adriamycin and methotrexate (FAMTX) in patients
      with previously untreated gastric cancer. Overall response rate, failure-free and
      overall survival were significantly improved with ECE, ECF also demonstrated
      improved quality of life and cost effectiveness when compared to the FAMTX
      regimen. ECF should now be regarded as the standard treatment for advanced
      oesophago-gastric cancer against which new therapies should be compared. In
      addition the Medical Research Council are conducting a trial randomising patients
      between surgery alone and perioperative chemotherapy using the ECF regimen in
      operable gastric cancer.

PMID- 9654593
TI  - Drug resistance in ovarian cancer - the role of p53.
AB  - The aims were to determine the importance of p53 and bcl-2 expression on the
      response to chemotherapy with alkylating agents in patients with ovarian cancer.
      We have followed the response to chemotherapy in a series of 59 patients with
      ovarian adenocarcinoma designated as p53 and bcl-2 positive or negative by
      immunocytochemistry. Of these cases, 50 received either cisplatin + treosulfan or
      treosulfan alone. Immunocytochemistry for p53 was positive in 28/59 tumors.
      Patients were grouped according to their response to chemotherapy (stable or
      progressive disease) assessed at 6, 12, and 18 months. There was increasing
      divergence of p53+ and p53- tumors over time. Of those which were p53+, 25%
      showed progression at 6 months, 80% at 12 months and 89% progression at 18
      months. In contrast, 23%, 50%, and 67% of p53- tumors showed progression at 6, 12
      and 18 months respectively. For bcl-2, in 23/55 positive tumors there was
      progression in 35%, 78% and 94% compared with 25%, 57% and 59% in bcl-2 negative
      tumors at 6,12 and 18 months respectively. Those tumors which were bcl-2 and p53
      negative were most likely to progress, while those which were bcl-2 and p53
      positive had the best prognosis. These differences did not translate into
      increased overall survival with minimum follow-up of 12 months. This data lends
      support to our suggestion that despite initially increased susceptibility to
      alkylating agents, enhanced genomic instability due to p53 inactivation may
      render tumors more likely to develop resistance to chemotherapy over time. This
      effect may be altered by bcl-2 function, lack of which will lead to a good
      response to chemotherapy as the tumor's ability to undergo apoptosis will not be
      compromised.

PMID- 9654594
TI  - Cathepsin D immunoreactivity in ovarian cancer: correlation with prognostic
      factors.
AB  - In view of the somewhat inconclusive nature of the reports of the role of
      Cathepsin D (Cath D) in ovarian carcinoma and its relationship with various other
      parameters of malignancy the present study was performed to aid in the further
      clarification of this role. One hundred freshly resected primary ovarian
      carcinomas of various histological types were studied for ER, PR and Cath D
      status and the results examined with respect to menopausal status, histology,
      size and lymph node invasion. In our series Cath D positivity was more frequent
      in serous than in other types of ovarian cancer but this Cath D positivity was
      not related to the frequency of lymph node invasion regardless of the size of the
      tumor. Nor was any association observed between Cath D positivity and ER or PR
      status of the tumors or the menopausal state of the patients. The reported
      prognostic value of Cath D, ER and PR is discussed as well as the distinction
      between tumor invasion by lymphatic channels and direct interstitial
      infiltration. It was concluded that Cath D may not play a role in the former mode
      but, as might be expected from its proteolytic properties, in local spread by
      means of tissue destruction.

PMID- 9654595
TI  - Cytokine sensitivity of metastatic human melanoma cell lines-- simultaneous
      inhibition of proliferation and enhancement of gelatinase activity.
AB  - The effect of a panel of cytokines on the proliferation and type IV collagenase
      production was studied in four melanoma cell lines of different origin,
      tumorigenicity and metastatic capacity. TGF-b, TNF-a and to a lesser extent, IL
      1a exhibited antiproliferative effect on the cell lines, with some lines showing
      varying degree of resistance. The sensitivity did not correlate directly with the
      origin or the biological behavior of the tumor lines, suggesting that cytokine
      resistance of advanced stage melanoma cells may be relative. IL-2, IL-10 and IL
      12 displayed little or no effect on proliferation. The effect of cytokines on
      metalloproteinase production showed a cell line dependent pattern. Interestingly,
      those cytokines that exhibited the most pronounced antiproliferative activity,
      also proved most effective in stimulating collagenase secretion, often
      simultaneously, in the same line. The results indicate that pleiotropic cytokines
      can have positive and negative effects simultaneously on various steps of tumor
      progression.

PMID- 9654596
TI  - Role for glucose transporter 1 protein in human breast cancer.
AB  - Glycolysis is increased in cancer cells compared with normal cells. It has been
      shown that glucose enters cells via a family of five functional glucose
      transporters (GLUT). However, GLUT expression appears to be altered in human
      breast cancer, which may serve as a selective advantage and facilitate the
      metastatic potential of these cells. The relationship of GLUT isoform expression
      and breast cancer cell invasiveness has not been adequately addressed. Thus, the
      purpose of this study was to investigate whether an association exists between
      GLUT expression and human breast cancer cell invasiveness. Invasiveness of the
      human breast cancer lines MCF-7, MDA-MB-435 and MDA-MB-231 was measured using an
      in vitro assay and compared with cellular GLUT isoform expression, assessed by
      Western blot analysis and verified by immunohistochemistry in a poorly
      differentiated human ductal breast cancer. Cell surface GLUT-1 expression was
      associated with the invasive ability of MCF-7 (2.0 + 0.02%), MDA-MB-435 (6.4 +/-
      0.4%), and MDA-MB-231 (19.3 +/- 2.0%). However, GLUT-2 and GLUT-5 were inversely
      associated with invasiveness; GLUT-3 expression was variable; and GLUT-4 was
      undetected. In a poorly differentiated human ductal breast cancer, in situ GLUT-1
      staining was intense. GLUT-1 expression was associated with the in vitro invasive
      ability of human breast cancer cells which was validated in situ. If this
      relationship is found to exist in a larger number of human breast cancer tissues,
      it may be possible to develop diagnostic and therapeutic strategies based on
      targeted GLUT isoform expression.

PMID- 9654597
TI  - Histidine decarboxylase in peripheral lymphocytes of healthy individuals and
      chronic lymphoid leukemia patients.
AB  - Histidine decarboxylase (HDC), the only enzyme capable of synthetizing histamine,
      has been found in many proliferating cells and tissues suggesting a role of
      histamine in cellular proliferation. In this study expression of HDC and the
      significance of histamine in the proliferation of peripheral lymphocytes of five
      healthy persons and six patients with chronic lymphoid leukemia (CLL) was
      examined. Expression of HDC mRNA and the protein was proved by reverse
      transcriptase polymerase chain reaction and by immunoblot, respectively. The role
      of histamine was studied in proliferation assays in the presence of irreversible
      inhibitor of the HDC (alpha-fluoromethylhistidine--aFMH) and also by competing
      for the intracellular binding sites of histamine using N,N-diethyl-2, 4
      phenylmethyl-phenoxy-ethanamine-HCl (DPPE). By inhibiting the HDC enzyme activity
      by FMH and blocking the intracellular action of histamine by DPPE, a significant
      decrease in cell proliferation was observed in mitogen stimulated lymphocytes of
      healthy donors. In CLL patients the proliferation of leukemic lymphocytes was
      significantly inhibited by blocking the binding of histamine to intracellular
      binding sites by DPPE but not by FMH inhibiting only the de novo histamine
      formation. The observations suggest that HDC has functional relevance in
      lymphocytes, since mitogen induced lymphocyte proliferation of healthy donors is
      mainly enhanced by de novo synthesis and subsequent action of intracellular
      histamine. Alternatively, in constitutively proliferating chronic lymphoid
      leukemia cells we suggest that the preformed pool but not the de novo synthesized
      intracellular histamine interferes with cellular proliferation.

PMID- 9654598
TI  - Lower cancer risk in medium high radon.
AB  - Radon exposure was shown to be carcinogenic and suggested as a possible causative
      factor for lung cancer in man. A hypothesis is introduced that medium high radon
      (between 110 and 165 Bq/m3) causes lower cancer risk among women younger than 61
      years, independent of the type of cancer. The presented results verify this
      statement with a probability of not less than 98%.

PMID- 9654599
TI  - Proliferative epithelial changes in ectopic gastric mucosa of Meckel's
      diverticula.
AB  - Twenty-one Meckel's diverticula containing an adequate amount of assessable
      heterotopic gastric mucosa were investigated for epithelial changes. Marked or
      moderate foveolar hyperplasia was present in 52% and 29% of the cases,
      respectively. Four cases displayed an excessive epithelial proliferation
      indefinite for dysplasia. It is pointed out that reflux type gastritis or
      gastropathy, which is the most common lesion in the ectopic gastric mucosa of
      Meckel's diverticulum, can be associated with the same confusing epithelial
      proliferation as reflux gastritis in the stomach, but these lesions are best
      regarded as representing atypia of repair. Distinguishing features from dysplasia
      are maturation towards the surface, lack of hyperchromatism and abscence of
      atypical mitoses. Negative p53 immunostaining and localization of the Ki-67
      positivity to the expanded neck region could be additive clues that can help to
      classify lesions indefinite for dysplasia as negative for dysplasia. On the basis
      of the similarities of the ectopic and ortotopic gastric mucosa, it is suggested
      that these additive clues previously used in other parts of the digestive tract
      could also apply for the stomach.

PMID- 9654600
TI  - Actin cleavage in various tumor cells is not a critical requirement for executing
      apoptosis.
AB  - Actin is a major cytoskeletal protein which is involved in many physiological
      cellular functions such as motility, cell shape, and adhesion. Recently, actin
      has also been reported to be cleaved by apoptotic proteases (i.e., caspases) and
      this cleavage is thought to contribute to the apoptotic process. However,
      conflicting data also exists as to whether actin represents a true caspase
      substrate during apoptosis induction in vivo (i.e., inside the cells). In this
      study, we critically examined the actin cleavage patterns during apoptosis of
      several tumor cell lines derived from three different species (i.e., mouse, rat,
      and human). Our findings demonstrate that: 1) actin cleavage in vivo is not a
      common phenomenon since apoptosis caused by multiple inducers in most cell types
      examined occurs without evidence of actin degradation; and 2) in certain cell
      types (e.g., U937), spontaneous, actin cleavage is observed which is not
      prevented by various specific chemical/peptide inhibitors of proteases such as
      caspases or serine proteases although apoptosis per se is retarded by some of
      these inhibitors. Our results conclude that actin is not a critical substrate for
      apoptotic proteases in vivo during apoptosis.

PMID- 9654601
TI  - Coccidioidomycosis in Hungary. The first import case.
AB  - A case of an isolated subcutaneous coccidioidomycosis in a 61-year-old man is
      presented. The patient has lived and worked in Arizona for 3 years previously but
      developed no apparent clinical signs of the disease. The painless, cavitating,
      tumor-like mass was surgically excised and the diagnosis was established by
      histological demonstration of the fungi and confirmed by serum
      counterimmunoelectrophoresis. This represents the first imported case of
      coccidioidomycosis in Hungary.

PMID- 9654602
TI  - Recent advances in molecular genetics of cardiovascular disorders. Implications
      for atherosclerosis and diseases of cellular lipid metabolism.
AB  - Two developments in molecular genetics will profoundly influence our
      understanding and the diagnosis of cardiovascular disorders. First, the
      identification of genes responsible for monogenic and polygenic traits by
      analysis of e.g. large pedigrees and affected sib pairs provides invaluable data
      regarding the role of specific genes in common diseases like arteriosclerosis,
      hypertension, diabetes, thrombosis/hemostasis and obesity. Besides the insights
      into the underlying pathophysiology, this knowledge will permit to identify
      persons at high risk for disease development. These patients can then obtain a
      targeted intervention. The second development is related to the availability of
      new analytical tools for molecular biology. New methods such as sequencing by
      hybridisation (SBH), DNA-array technology or matrix assisted laser
      desorption/ionisation-time of flight mass spectroscopy (MALDI-TOF) permit
      sequence analysis of complete genes within hours. Automated PCR-technologies with
      homogenous amplicon detection formats simplify PCR and permit its use in the
      routine laboratory setting. Considering cardiovascular diseases there is a number
      of genes involved in lipid metabolism (apolipoproteins, lipoprotein receptors,
      lipolytic enzymes), thrombosis/hemostasis (platelet receptors, pro- and
      anticoagulant proteins, fibrinogen, PAI's), hypertension (angiotensin converting
      enzyme, angiotensinogen) glucose metabolism (glucose transporters, enzymes) and
      obesity (hormones, receptors), that are interesting candidates for sophisticated
      genetic risk assessment. Furthermore, there are also gene candidates involved in
      processes of early atherogenesis and chronic inflammation such as complement
      proteins, cell adhesion molecules, and cellular receptors and enzymes. Most of
      these gene candidates were derived from pathophysiologic knowledge and subsequent
      epidemiological studies. However, it is foreseeable that in the coming years
      genes will be identified which were not known so far to be involved in
      cardiovascular diseases. Genetic studies will be of prime importance in this
      area, as is exemplified by animal models. In the long term, analysis of these
      candidate genes before the implementation of therapy will permit a targeted
      intervention approach towards high risk patients. This will reduce the overall
      costs of health care without reducing the quality.

PMID- 9654603
TI  - Endothelial dysfunction in preeclampsia.
AB  - Several years ago the hypothesis was advanced that alterations of endothelial
      function could explain much of the pathophysiology of preeclampsia. Since that
      time, extensive data have been generated to support the hypothesis. Markers of
      endothelial activation can be demonstrated in women with overt preeclampsia. More
      importantly, many of these markers precede clinically evident disease and
      disappear with resolution of the disease. The original postulate was that
      materials produced by the poorly perfused placenta, which is characteristic of
      preeclampsia, entered the systemic circulation and altered endothelial cell
      activity. This was proposed to change vascular sensitivity to circulating
      pressors, activate coagulation, and reduce vascular integrity resulting in the
      pathophysiological changes of preeclampsia. As data have accumulated it has
      become increasingly evident that the insult to the endothelium is neither
      toxicity nor nonspecific injury but rather can better be characterized as
      endothelial activation. Candidate molecules have been suggested but not
      established. It seems likely that the responsible agent(s) will not be unique
      molecules but rather usual molecules present in excessive amounts. The hypothesis
      has been expanded to invoke involvement of the maternal constitution in the
      generation of endothelial injury and injurants. This concept is stimulated by the
      observation that reduced placental perfusion per se is not sufficient to generate
      the maternal syndrome. Women with growth-restricted fetuses frequently are not
      preeclamptic. Placental bed biopsies from not only growth-restricted but also
      prematurely born infants demonstrate failure of the physiological remodeling of
      decidual vessels responsible for the reduced placental perfusion of preeclampsia.
      This has led to the concept that preeclampsia is secondary to an interaction of
      reduced placental perfusion and maternal factors. Interestingly these maternal
      factors, obesity, insulin resistance, black race, hypertension, and elevated
      plasma homocysteine concentration are all risk factors for atherosclerosis in
      later life.

PMID- 9654604
TI  - Circulating factors as markers and mediators of endothelial cell dysfunction in
      preeclampsia.
AB  - During the past decade a new hypothesis has been formulated that explains many of
      the disparate findings associated with the pregnancy syndrome preeclampsia. With
      an increased awareness of the physiological significance of vascular endothelial
      cell function, the seemingly unrelated signs of hypertension, proteinuria, edema,
      and hypercoagulability have converged to provide clinical evidence of a unifying
      pathophysiological mechanism: systemic, maternal endothelial cell dysfunction.
      Investigators have attempted to test this hypothesis through two approaches. The
      first approach involves the identification of in vivo markers of vascular
      endothelial cell injury in women with clinically evident preeclampsia. The second
      approach focuses on the ability of circulating factors derived from the serum or
      plasma of patients afflicted with preeclampsia to perturb endothelial cell
      function in vitro. In this review we summarize the increasingly compelling
      evidence that maternal vascular endothelial cells are a critical target for toxic
      humoral activities that precipitate the multifaceted preeclampsia syndrome.

PMID- 9654605
TI  - Plasma lipids and vascular dysfunction in preeclampsia.
AB  - The dominating hypothesis of the preeclampsia syndrome (PES) is that placentally
      derived factors are released to the maternal circulation. These factors are
      believed to alter endothelial properties resulting in disturbed vasomotor
      function, increased endothelial permeability, and activation of thrombogenic
      factors. However, the impact of placentally derived factors on the endothelial
      cells is influenced by another major variable: the "sensitivity" of the maternal
      endothelium to the placental factors. Several maternal factors may play a role in
      determining this sensitivity. They include chronic hypertension, diabetes, and
      hyperlipidemia. In this article we discuss the possible role of hyperlipidemia
      (especially high free fatty acids and hypertriglyceridemia) in the pathogenesis
      of preeclampsia, viewed from this perspective. Pregnancy in general, preeclamptic
      pregnancy in particular, is associated with a marked hyperlipidemia. We suggest a
      parallel to atherosclerotic diseases, wherein hyperlipidemia induces endothelial
      dysfunction, probably by promoting oxidative stress in the arterial wall. The
      hyperlipidemia of pregnancy may have a similar effect on the endothelial cells.
      When placentally derived endothelial disturbing factors, like lipid peroxides and
      trophoblastic components, are released into the maternal circulation, their
      effects on the endothelium may be enhanced because of hyperlipidemia-mediated
      activation or "sensitization" of the endothelial cells. Alternatively,
      placentally derived factors like peroxides may combine with lipoproteins, forming
      complexes that are more disturbing to cells than the placental factors or
      lipoproteins are individually. We also discuss the possible role of maternal
      hyperlipidemia in aggravating placental insufficiency caused by poorly
      transformed spiral arteries. The hemodynamic flow pattern may be markedly
      different in completely and incompletely transformed spiral arteries. By analogy
      to the fundamental role of hemodynamic factors in development of atherosclerosis,
      we pose the hypothesis that abnormally transformed spiral arteries have an
      "atherogenic" blood flow pattern that promotes lipid deposition and "acute
      atherosis".

PMID- 9654606
TI  - Insulin resistance syndrome in preeclampsia.
AB  - Because changes in lipids, lipoprotein, and other metabolic processes, such as
      hyperinsulinemia and hyperuricemia, found in preeclampsia resemble the main
      features of the insulin resistance syndrome, it has been proposed that insulin
      resistance may be the common denominator for such metabolic changes. Several
      groups, using euglycemic-hyperinsulinemic clamping or intravenous glucose
      tolerance tests (Bergman's minimal model technique), have demonstrated insulin
      resistance during late pregnancy. Women with preeclampsia had higher fasting
      insulin levels, but also exaggerated hyperinsulinemia, in response to an oral
      glucose tolerance test, which is consistent with increased insulin resistance in
      preeclampsia. No direct measurement of insulin sensitivity (clamp or minimal
      model) has as yet been performed during preeclampsia. Increased insulin
      resistance can activate the sympathetic nervous system and lead to an increase in
      expression of receptors for endothelin, both of which events lead to increased
      blood pressure. Hyperinsulinemia can also induce hypertriglyceridemia, leading to
      endothelial dysfunction and reduction of prostacyclin production. This
      hyperinsulinemia can persist for as long as 17 years after preeclamptic pregnancy
      and may contribute to a woman's increased risk of cardiovascular disease. Insulin
      resistance may not be the cause of preeclampsia, but is one of the pathogenic
      factors, especially in genetically predisposed women.

PMID- 9654607
TI  - Antioxidants and inflammatory cell response in preeclampsia.
AB  - There is widespread evidence of inflammatory cell and antioxidant activity in
      preeclampsia. However, it is difficult to disentangle the pathological changes
      from the normal physiological responses to the pathological process. The site at
      which the measurements are taken, and the severity of disease, alter the results.
      The interaction between the mother and the fetus needs to be considered
      separately, especially when the genetics of preeclampsia is considered. It is
      clear that within the placenta, there is an increase in tumor necrosis factor
      alpha (TNF-alpha) and lipid peroxide production. These changes are associated
      with a reduction in the various placental antioxidants. This suggests there may
      be a failure of the normal fetal protection systems. Lipid peroxidation is also
      increased in the peripheral blood, as well as IL-6, IL-8, and TNF-alpha, which
      are of monocytic origin. Stimulated monocytes produce free radicals, which can
      cause oxidative damage. Maternal cells protect themselves with both plasma and
      intracellular antioxidants. There is an imbalance between oxidant and antioxidant
      activity in preeclampsia. Changes in membrane oxidation can lead to changes in
      the membrane stability. Genetic difference in the production of TNF-alpha and
      nitric oxide may also modify the disease process, demonstrating the role for
      "moderator genes."

PMID- 9654608
TI  - The neutrophil and preeclampsia.
AB  - Endothelial injury is common to all pathological features of preeclampsia.
      Neutrophil activation has been implicated in the pathophysiology of preeclampsia
      and requires binding and transmigration of neutrophils through the endothelium.
      This occurs via an interaction of endothelial adhesion molecules and surface
      receptors on neutrophils. Upon activation, neutrophil granules are released, the
      contents of which are capable of mediating vascular damage. In addition,
      leukotrienes are synthesized, and superoxide is generated in a respiratory burst.
      These products also provoke vascular damage. Neutrophil recruitment to the
      endothelium involves express of P-selectin and released of platelet activating
      factor from the endothelium. In preeclampsia there is evidence of an increase in
      neutrophil activation with up-regulation of neutrophil integrin expression and
      increased regulation of the protease elastase. Furthermore, these markers of
      neutrophil activation correlate with established markers of disease severity. The
      primary mechanism of neutrophil activation is unknown, but neutrophils in
      preeclampsia appear to have normal motor activity. Several potential mechanisms
      of neutrophil activation have been identified. They include up-regulation of
      cellular adhesion molecules on the endothelial surface, increased generation of
      tumor necrosis factor-alpha, and endothelial activation from hyperlipidemia. In
      additional to activation of neutrophils in preeclampsia, there may be involvement
      of the interleukin-6 and endothelin-1 in "priming" neutrophils for subsequent
      superoxide production. Activated neutrophils are likely to play a large part in
      the arteriopathy and endothelial damage associated with preeclampsia, but it is
      unclear whether neutrophil activation is the cause or the consequence of
      endothelial damage.

PMID- 9654609
TI  - Oxidative stress and altered endothelial cell function in preeclampsia.
AB  - Evidence continues to accumulate that oxidative stress is a mediator of
      endothelial cell dysfunction and thus contributes to the cardiovascular
      complications of preeclampsia. The mechanisms for the interaction of oxidative
      stress and endothelial cell function have not been well defined. This review
      explores potential vasoactive pathways that may be affected by oxidative stress
      and have been reported to be altered in women with preeclampsia. In pathologic
      conditions of oxidative stress, increased production of superoxide peroxide
      anions and nitric oxide has been recognized to inactivate the nitric oxide as a
      vasorelaxant as well as produce peroxynitrite, a potent oxidant. Increase
      prostaglandin H (PGH) synthase activity resulting in vasoconstriction
      predominates in models of oxidative stress. Peroxynitrite increases PGH synthase
      activity in vitro, providing a potential, but as yet untested, link between
      oxidative stress, nitric oxide, and PGH synthase pathway, leading to reduced
      relaxation and increased constriction in the vasculature of women with
      preeclampsia. Other vasoconstrictors (such as isoprostanes and endothelin) that
      may be interrelated with oxidative stress and altered endothelial cell function
      in preeclampsia are also discussed.

PMID- 9654610
TI  - Dyslipidemia, iron, and oxidative stress in preeclampsia: assessment of maternal
      and feto-placental interactions.
AB  - The etiology and pathogenesis of the pregnancy syndrome preeclampsia remain
      poorly understood. There is evidence that oxidative stress (am imbalance between
      oxidant and antioxidant forces in favor of oxidants) occurs in preeclampsia, and
      it has been hypothesized that reactive oxygen species or their metabolites
      ultimately comprise the "defensive" vasodilatory, antiaggregatory, and barrier
      functioning of the vascular endothelium. Oxidative stress may be point at which
      feto-placental and maternal factors converge, resulting in the protean
      manifestations of preeclampsia. This review highlights the evidence for maternal
      dyslipidemia and altered iron kinetics in preeclampsia and gives a critical
      assessment of their potential impact on disease progression. The theme is
      developed that interaction of maternal components, particularly neutrophils and
      oxidation-susceptible lipids, with placental cells and placental-derived factors
      engenders feed-forward cycles of oxidative stress that ultimately cause
      widespread endothelial cell dysfunction and its clinical manifestations.

PMID- 9654611
TI  - Maternal-placental interactions of oxidative stress and antioxidants in
      preeclampsia.
AB  - This review addresses the general hypothesis that the pathogenesis of
      preeclampsia is related to an imbalance of increased oxidative stress and lipid
      peroxidation coupled to a deficiency of antioxidant protection. Evidence will be
      presented that this imbalance is present in both the maternal compartment and the
      placental compartment and that interactions between these two compartments result
      in the clinical manifestations of this disorder. We suggest the following as a
      scenario for the development of preeclampsia: Oxidative stress in the maternal
      compartment affects the placenta in such a way as to bring about a decrease in
      placental antioxidant enzyme protection. The oxidative stress in the maternal
      compartment may be preexisting (e.g., obesity, diabetes, hyperlipidemia) or may
      be caused by placental secretion of lipid peroxides. Decreased placental
      antioxidant enzyme protection leads to a cascade of events in the placenta of
      uncontrolled lipid peroxidation with increased thromboxane production and
      increased tumor necrosis factor (TNF-alpha) production. Increased placental
      secretion of lipid peroxides and/or TNF-alpha results in activation of leukocytes
      as they circulate through the intervillous space. The activated leukocytes serve
      as circulating mediators that link the increased oxidative stress of the placenta
      with a widespread increase in oxidative stress and endothelial dysfunction in the
      mother. In the third trimester, when the placenta is growing rapidly, the
      mother's antioxidant capacity is no longer able to compensate, and the clinical
      symptoms of preeclampsia appear.

PMID- 9654612
TI  - Measuring HIV/AIDS case management.
AB  - Studies of HIV/AIDS case management have been limited by their almost exclusive
      focus on adults and by the limitations of available methodologies. This study
      assesses the use of a time study methodology to measure the case management
      activities of 20 case managers in two urban hospital pediatric and adult HIV/
      AIDS clinics and in 3 community organizations. Case management activity was
      sampled using a beeper case managers carried, which signaled randomly 8 times a
      day over 5 consecutive days. When the signal "beeped", case managers checked on a
      form the appropriate descriptor of their involvement in case management tasks and
      with different clients. The results suggest that the Time Study methodology is a
      useful and valid way of measuring case management.

PMID- 9654613
TI  - Measuring case management for families with HIV.
AB  - Case management has been recognized as a major way for coordinating the multiple
      services needs for people with HIV/AIDS. Such coordination is required because of
      the progressively debilitating nature of this chronic disease and the fragmented
      health care and social services delivery system. One of the major problems with
      the study of case management is the difficulty in actually measuring it. Another
      major limitation has been the focus almost exclusively on adult models of
      HIV/AIDS case management. This study was undertaken to assess the efficacy of a
      time study methodology to measure differences in case management activities when
      case managers work with families and when they work with individuals. Ten case
      managers from two urban hospital pediatric and adult HIV/AIDS clinics and 10 case
      managers from 3 community organizations participated. Case management activity
      was sampled using a beeper carried by case managers which signaled randomly 8
      times a day over 5 consecutive days. When the signal "beeped", case managers
      checked off on a 1-page form the appropriate descriptor of their involvement
      concerning task initiation, interaction, location, type, function as well as
      information about client needs, HIV status, and family history. The results
      suggest that the Time Study methodology is a useful and valid way of measuring
      case management and of identifying differences in case mix, client need and
      background, and case management techniques when case managers work with families
      and with individuals.

PMID- 9654614
TI  - An off-site orientation program for medical social workers.
AB  - The health care system is a complex and demanding environment requiring an
      acculturation process for all those who provide services under its aegis. Social
      workers new to a medical setting, are faced with difficulties relating to all
      aspects of their role: bureaucratic, professional and clinical. In an attempt to
      ease their entry into the health care system, five social work administrators,
      employed by the largest HMO in Israel, structured and facilitated an off-site
      orientation program for new workers. A core group of 22 social workers
      participated in the program, and in the final session, the participants evaluated
      the course verbally and in an anonymous closed questionnaire. Feedback was mixed
      and included the participants dissatisfaction with the reduction of the
      experiential component of the sessions.

PMID- 9654615
TI  - Family conferences as forums for decision making in hospital settings.
AB  - Social workers in hospitals are often involved in family conferences where
      patient, family members and hospital personnel meet together to exchange
      information about the patient's condition and to plan for the future. In this
      paper the complexities of these meetings as decision making arenas are discussed
      and an outline of the three phases of family conferences--preparation, the
      conference meeting and follow up--is presented. The final section reports on an
      exploratory review of recent conferences as perceived by social workers from an
      acute and rehabilitation teaching hospital. The social workers' comments indicate
      that the conferences achieve the desired outcomes, especially for hospital staff.
      In this hospital the conferences are more often used for providing family members
      with information, and for collective decision making about the patient's future
      care, than for providing information to the patients about their illness and
      treatment.

PMID- 9654616
TI  - Self-care and psychosocial adjustment of patients following cardiac surgery.
AB  - This research examined the role of self-care behavior of 151 patients (aged 40 to
      80) on general psychological distress at one year after coronary artery bypass
      graft (CABG) surgery. A tested hypothesis was that self-care practices would be
      associated with a lower level of distress one year after surgery. The results
      supported the beneficial effect of self-care on psychological adjustment, after
      controlling for the effects of the number of other chronic illnesses and post
      CABG depression. The findings suggest that social work in health care and in-home
      care may help promote the psychosocial recovery process following surgery.

PMID- 9654617
TI  - Psycho-social aspects of serious renal disease and dialysis: a review of the
      literature.
AB  - The most severe form of kidney disease is renal failure, a life-threatening
      condition known as end-stage renal disease (ESRD). Though social work
      intervention is an integral part of the response to serious kidney disease, the
      topic has been noticeably absent in the discipline's literature. This article
      synthesizes the research on the psycho-social aspects of end-stage renal disease,
      with a particular focus on dialysis patients at different stages of the life
      cycle. Social work services are particularly important to dialysis patients
      because (1) ESRD influences patients' psycho-social environments and (2) the
      psycho-social environments in which ESRD sufferers live impact the course of the
      disease and physical well-being. Intervention issues are discussed. The review
      found that most research on this topic lacks adequate sampling to generalize to
      the ESRD population. Future research needs to address this shortcoming and
      increase sample sizes to allow for statistical controls.

PMID- 9654618
TI  - Phospholipase A2 sensitivity of the dorsal root and dorsal root ganglion.
AB  - STUDY DESIGN: This study was designed to characterize the effects of
      phospholipase A2 on the neural response of dorsal root and dorsal root ganglion
      in the anesthetized New Zealand White rabbit. OBJECTIVES: To examine the effects
      of phospholipase A2 on the neural response of somatosensory neurons at the dorsal
      root ganglion level. SUMMARY OF BACKGROUND DATA: Phospholipase A2 may be an
      irritating component of disc tissue that is present in high concentration in
      painful herniated discs, in synovial fluids, and in sera of rheumatoid arthritis
      patients. Phospholipase A2 is inflammatory; however, its effects on dorsal roots
      and dorsal root ganglion response have never been demonstrated. METHODS:
      Surgically isolated dorsal roots and dorsal root ganglia from New Zealand White
      rabbits were investigated by electrophysiologic techniques. Phospholipase A2
      doses ranging from 100 to 400 U were applied on the mechanically sensitive
      segments of the dorsal root ganglia, and responses to varying doses were
      evaluated in relation to elapsed time. RESULTS: The application of phospholipase
      A2 on the dorsal root ganglion resulted in possible neurotoxicity at doses more
      than 375 U, with no significant effect at lower doses except for recruitment of
      "silent units" at doses ranging from 200 to 340 U. CONCLUSIONS: Phospholipase A2
      doses comparable to serum concentrations in human rheumatoid arthritis appeared
      to be neurotoxic when applied to dorsal root ganglia. At lower doses, silent
      units become activated that were not active before the phospholipase A2
      application. These results suggest that dorsal roots and dorsal root ganglion may
      be impaired by phospholipase A2, leading to sciatica and low back pain.

PMID- 9654619
TI  - Biomechanical evaluation of translaminar facet joint fixation. A comparative
      study of poly-L-lactide pins, screws, and pedicle fixation.
AB  - STUDY DESIGN: Nine sheep cadaveric spines were used in this acute postoperative
      model. OBJECTIVES: To compare the biomechanical performance of translaminar facet
      joint fixation techique with that of cortical screws and bioabsorbable poly-L
      lactide pins and with that of rigid pedicle screw fixation in the lumbar spine.
      SUMMARY OF BACKGROUND DATA: Among numerous posterior spine fixation techniques,
      pedicle screw fixation has been reported to be the most rigid construct and to
      provide high fusion rate. Translaminar facet joint screw fixation is an
      alternative to pedicle screw fixation and is the lowest profile construct that
      achieves stabilization. The authors have developed a new concept involving
      application of bioabsorbable poly-L-lactide pins to translaminar facet joint
      fixation. Degradation in the stiffness of the implants with time may be
      advantageous for fusion mass remodeling. METHODS: A total of nine sheep L2-L6
      cadaveric spines were used. Each intact spine was nondestructively tested in
      flexion-extension bending (+/- 5-Nm peak bending moment with 100-N axial
      compression) on a modified testing machine. Loads were applied for 10-second
      periods using sinusoid waveforms. After testing the intact spine, bilateral
      fenestration was performed between L4 and L5 and the medial aspect of the facet
      capsule was resected. The L4-L5 functional spinal unit was than stabilized by
      five methods: translaminar facet joint fixation with smooth poly-L-lactide pins;
      translaminar facet joint fixation with cortical screws; pedicle screw fixation
      with the Texas Scottish Rite Hospital system; and without instrumentation, in
      that order. Linear displacement of L4 inferior and L5 superior articular
      processes in the sagittal plain (delta facet) and L4-L5 intervertebral rotation
      in the sagittal plain (theta sagittal) were measured by the extensometers mounted
      to the spine. Ranges of motion (delta facet and theta sagittal), neutral zones,
      linear elastic zone stiffness, and the total energy absorption during the load
      unload cycle (hysteresis) were calculated. RESULTS: By resecting the facet joint
      capsules and ligamentum flavum, delta facet and theta sagittal were not increased
      significantly, whereas the increase of neutral zones and hysteresis were
      statistically significant. Compared with the intact spine, delta facet was
      significantly reduced to 41% of normal with translaminar facet joint fixation
      with poly-L-lactide pins, to 9% with translaminar facet joint fixation with
      screws, and to 11% with the Texas Scottish Rite Hospital system. Neutral zones of
      delta facet showed a similar pattern, and these differences were significant.
      Regarding linear elastic zone stiffness, translaminar facet joint fixation with
      screws provided a stiffer construct than did pedicle screw fixation in the
      flexion loading mode, whereas pedicle screw fixation yielded higher values for
      stiffness in extension loading. Translaminar facet joint fixation with poly-L
      lactide pins increased linear elastic zone stiffness in extension loading, but
      the increase was less than was achieved with the other constructs. CONCLUSIONS:
      The facet joint is the only true articulation in the lumbosacral spine. It is
      logical to fix this part directly to achieve spine fixation. Translaminar facet
      joint fixation with screws show similar biomechanical performance to pedicle
      screw fixation. Translaminar facet joint fixation with poly-L-lactide pins is
      significantly less stiff than either type of screw fixation, but it also
      restricts the facet joint and intervertebral motions significantly when compared
      with the intact spine.

PMID- 9654620
TI  - Morphometry of human neck muscles.
AB  - STUDY DESIGN: Cadaveric dissections were used to study muscle morphometry.
      OBJECTIVE: To describe systematically the musculotendinous lengths, fascicle
      lengths, pennation angles, and physiologic cross-sectional areas of neck and
      shoulder muscles implicated in head movement. SUMMARY OF BACKGROUND DATA: In
      previous studies of neck-muscle anatomy, researchers described only a subset of
      muscle features, often using crude or indirect methods. None used microdissected
      muscles to correct measured parameters for the presence of multiple fiber
      compartments, internal aponeuroses, or variations in fiber or sarcomere length
      required for qualitative models of force-generating capabilities. METHODS: Muscle
      mass, pennation angle, fascicle length, and sarcomere length were measured in 14
      neck muscles from 10 human cadavers. Architecturally complex muscles with
      multiple attachments were divided into subvolumes, and each subvolume was
      examined from both the superficial and deep surfaces, Internal aponeuroses were
      microdissected within muscles to characterize architectural specializations.
      Physiologic cross-sectional areas were calculated from the morphometric data.
      RESULTS: The neck musculature was architecturally complex. Many muscles crossed
      two or more joints and had multiple attachments to different bones. In some, the
      presence of tendons and aponeuroses was associated with specializations in
      fascicle organization. Considerable interindividual variation was found in the
      number and location of tendinous insertions of the scalenes and longissimus
      capitis muscles. In addition, rhomboideus showed significant variations in its
      size and shape. The cross-sectional areas of neck muscles from large and small
      subjects did not scale proportionately with body height and weight, nor did
      individual muscles with widely varying cross-sectional areas (0.3-15.3cm2) scale
      from on subject to another. CONCLUSIONS: The accuracy of morphometry can be
      improved by incorporating measurements made by microdissecting neck muscles. The
      presence of aponeurotic attachments can greatly shorten fascicle length; failure
      to identify such attachments can lead to underestimates of cross-sectional areas.
      Accuracy of a generalized model of the neck is also improved by normalizing
      sarcomere lengths in all muscles.

PMID- 9654621
TI  - Shen instrumentation for the management of unstable thoracolumbar fractures.
AB  - STUDY DESIGN: A retrospective study was carried out using Shen instrumentation,
      which is a modified pedicle rod sleeve spinal system, to perform reduction and
      fusion in patients with unstable thoracolumbar fracture. OBJECTIVES: To
      demonstrate that the simple, locally made pedicle rod sleeve instrumentation is
      as effective as conventional systems in the management of thoracolumbar
      fractures. The current results are also compared with those reported in the
      literature. SUMMARY OF THE BACKGROUND DATA: Many instrumentations, such as
      Harrington, Luque, and Dick, have been used for the management of thoracolumbar
      fracture in the past 2 decades. Every device has its advantages and disadvantages
      based on clinical practice and the biomechanical mechanism of reduction. METHODS:
      Between January 1991 and December 1995, 96 consecutive patients who had
      experienced unstable thoracolumbar fractures were treated surgically with Shen
      instrumentation, which consists of four components: superior pedicle screws,
      distraction rods, sleeves, and inferior laminar hooks. Of these 96 patients, 76
      were male and 20 were female (age range, 16-68 years; mean, 37 years). Thirty
      patients had partial paraplegia and 38 patients had complete paraplegia,
      according to the Frankel classification. Injury categories were as follows: 43
      burst fractures, 26 flexion-compression fractures, 22 fracture-dislocation
      injuries, and 5 flexion-distraction injuries. RESULTS: The average follow-up was
      39 months (range, 24-60 months). Kyphotic deformity was corrected from 27.1
      degrees before surgery to 4.2 degrees after surgery, translation was reduced from
      30.7% to 0%, height of compressed vertebral bodies was restored from 52.3% to
      96.5% of the normal height. Computed tomographic evaluation showed that the cross
      canal area was restored from 48.1% before to 70.9% after surgery. Improvement of
      neurologic function of more than one Frankel grade occurred in 90% of patients.
      CONCLUSION: Based on the understanding of biomechanics and the present clinical
      results, Shen instrumentation is as efficacious as conventional devices available
      today and may serve as a cost-effective option for thoracolumbar injuries,
      especially in a developing country.

PMID- 9654622
TI  - Video-assisted thoracoscopic surgery versus open thoracotomy for anterior
      thoracic spinal fusion. A comparative radiographic, biomechanical, and histologic
      analysis in a sheep model.
AB  - STUDY DESIGN: In this in vivo investigation, a sheep model was used to compare
      the efficacy of a video-assisted thoracoscopic approach and a traditional
      thoracotomy in promoting a successful interbody spinal arthrodesis. OBJECTIVES:
      To compare the incidence of successful anterior spinal arthrodesis among three
      stabilization techniques-iliac crest, Bagby and Kuslich device, and Z-plate-
      performed using a video-assisted thoracoscopic approach and conventional open
      thoracotomy approaches. SUMMARY OF BACKGROUND DATA: A clinical outcome study on
      open versus endoscopic spinal fusion is not yet available. Moreover, no basic
      scientific investigations have been conducted to determine whether the success of
      an endoscopic arthrodesis is comparable to that of a conventional open procedure.
      METHODS: Fourteen Western Crossbred sheep underwent three identical
      destabilization procedures at T5-T6, T7-T8, and T9-T10, in which the anterior and
      middle osteoligamentous columns of the spine were resected, followed by three
      randomized reconstruction procedures using iliac autograft alone, and Z-plate
      stabilization with iliac autograft. In seven sheep, the entire destabilization
      reconstruction procedure was performed using a video-assisted thoracoscopic
      surgical approach. In the remaining seven, the procedure was performed by
      conventional open thoracotomy. RESULTS: Histomorphometric and biomechanical
      evaluation demonstrated that the video-assisted thoracoscopic approach and open
      thoracotomy arthrodesis had comparable bone formation and biomechanical
      properties (P > 0.05). However, the Z-plate fusions, as a group, demonstrated
      increased flexion-extension stiffness properties and trabecular bone formation
      compared with the autograft and Bagby and Kuslich device fusions (P < 0.05).
      CONCLUSIONS: Thoracic interbody spinal fusions performed by thoracoscopy have
      demonstrated histologic, biomechanical, and radiographic equivalence to those
      performed by a thoracotomy approach. However, in the endoscopy group,
      intraoperative complications causing longer operative times, higher estimated
      blood loss, and increased animal morbidity indicated a substantial learning curve
      associated with the adoption of this surgical technique.

PMID- 9654623
TI  - The lordotic effect of the OSI frame on operative adolescent idiopathic scoliosis
      patients.
AB  - STUDY DESIGN: A prospective evaluation of adolescent idiopathic scoliosis
      patients undergoing operative treatment on the Orthopedic Systems Incorporated
      (OSI; Jackson) frame. OBJECTIVES: To investigate prospectively thoracic,
      thoracolumbar, and lumbar sagittal alignments in patients with adolescent
      idiopathic scoliosis who undergo an instrumented posterior spinal fusion on the
      OSI frame. SUMMARY OF BACKGROUND DATA: In several studies, it has been shown that
      patient positioning on various operative frames is an important component of
      ultimate lumbar sagittal alignment. However, these studies have all concentrated
      on the lumbar spine, and no sagittal plane alignment data in adolescent
      idiopathic scoliosis patients have been reported in the thoracic and
      thoracolumbar junction as it relates to intraoperative positioning, correction
      maneuvers and correlative postoperative results. METHODS: Thirty-nine patients
      with operative adolescent idiopathic scoliosis treated with an instrumented
      posterior spinal fusion on the OSI frame were prospectively evaluated. Standing
      preoperative, intraoperative, and postoperative long-cassette lateral radiographs
      were reviewed with regional and segmental Cobb measurements of the thoracic,
      thoracolumbar junction, and lumbar spine obtained. RESULTS: Thoracic kyphosis (T1
      T12) measured +34 degrees before surgery, +28 degrees during surgery, and +30
      degrees after surgery, Thus, a statistically significant decrease was noted in
      thoracic kyphosis secondary to prone positioning on the OSI frame ( P < 0.05).
      Thoracolumbar spine measurements from T10 to L2 also showed a lordotic trend from
      +2 degrees before surgery, to -4 degrees during surgery, to -8 degrees after
      surgery, which was also statistically significant (P < 0.05). Total lumbar
      lordosis from T12 to S1 remained relatively unchanged from -60 degrees before
      surgery, to -59 degrees during surgery, to -60 degrees after surgery. However,
      segmental lumbar lordosis measured from T12 to the lowest instrumented vertebra
      showed a statistically significant increase in lordosis from -17 degrees before
      surgery, to -19 degrees during surgery, to -23 degrees after surgery (P < 0.05).
      Those patients in whom lumbar pedicle screws were used (vs. hooks alone) had the
      greatest increase in lumbar instrumented lordosis. CONCLUSIONS: Performing
      adolescent idiopathic scoliosis correction on the OSI frame tends to decrease
      thoracic kyphosis, increase thoracolumbar lordosis, and increase segmental
      instrumented lumbar lordosis, while it maintains total lumbar lordosis.

PMID- 9654624
TI  - An unusual cause of low back pain? A case report.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To highlight the evaluation of a patient
      with low back pain after an incidental radiographic finding clouded routine
      management. SUMMARY OF BACKGROUND DATA: Greenfield filters have been used for 20
      years with good results. Complications have been seen and documented, but the
      natural history of filter placement in young patients is not fully appreciated. A
      prong from a Greenfield filter embedded within a vertebral body has been reported
      once as an incidental finding in a patient undergoing prophylactic monitoring for
      recurrence of tumor. METHODS: A 31-year-old woman had a pulmonary embolus after
      surgery for a benign adnexal mass. A bleeding complication occurred after
      systemic anticoagulation, and a vena caval filter was placed to limit the
      possibility of further emboli. The patient was referred to the orthopedic clinic
      5 years later with low back pain and an unusual finding on computer tomographic
      scan: One prong of the filter was embedded within a vertebral body. RESULTS: A
      bone scan was obtained to evaluate the status of bone activity around the prong.
      Bone reaction was not evident. Conservative management of her low back pain was
      instituted, and after 2 years, the patient remains asymptomatic. CONCLUSION: The
      overall use of vena caval filters has produced favorable results, although
      numerous complications have been reported. All long-term sequelae have not been
      completely identified.

PMID- 9654625
TI  - Vertebral remodeling in eosinophilic granuloma of the spine. A long-term follow
      up.
AB  - STUDY DESIGN: In this study, 14 conservatively treated patients were reviewed who
      had eosinophilic granuloma of the spine, which had been diagnosed on the basis of
      histologic study of the vertebral lesion or of specimens from other sites in
      patients with multiple involvement. The remodeling of the vertebral body was
      studied in an average follow-up of 5.6 years. OBJECTIVES: To analyze the
      remodeling process of the involved growing vertebral body in Langerhans Cell
      Histiocytosis after conservative treatment and to assess the sagittal and frontal
      profile of the spine at the end of growth. Fourteen patients, aged between 1.2
      and 11.3 years, with spinal involvement of a Langerhans' cell histiocytosis were
      treated in the department of orthopedics between 1980 and 1990. All patients had
      immobilization of the affected region by a custom-made brace. Six patients with
      symptomatic lesions had radiotherapy and four patients with disseminated disease
      were treated with chemotherapy. Clinical and radiologic examinations were made at
      regular intervals to evaluate the development of the vertebrae during the
      remodeling process. SUMMARY OF BACKGROUND DATA: In the 14 patients, both sexes
      were affected equally. The disease was located in the cervical spine in two
      patients and in thoracic and lumbar vertebrae in seven patients each. Two
      patients had two vertebral lesions. METHODS: The radiologic evolution of the 16
      vertebral lesions was evaluated using follow-up standardized lateral radiographs.
      The reconstitution of the vertebral height in the presence of vertebra plana was
      calculated by measuring the ventral distance between the superior and inferior
      margins of the vertebral body in relation to the adjacent uninvolved vertebra.
      RESULTS: The measurements showed a growth rate of 1.5-6 (average, 3) in vertebrae
      with vertebra plana and a growth rate of 1.1-2.7 (average, 1.4) in the unaffected
      vertebra. The reconstitution of the vertebral height was between 18.2% and 63.8%
      of the adjacent vertebrae before and between 72.2% and 97% after skeletal
      maturity. CONCLUSIONS: The results demonstrate that conservative orthopedic
      treatment with immobilization in a brace is sufficient to allow for optimal
      vertebral remodeling. Partial to nearly complete reconstitution of vertebral
      height was seen in all cases. Thus, operative treatment with curettage of the
      lesion and bone grafting including multisegmental fusion with instrumentation is
      not necessary. In instances with neurologic impairment, rarely seen in adults,
      surgical decompression and short fusion of the spine is necessary. Nevertheless,
      complete staging and biopsy are mandatory for an accurate diagnosis.

PMID- 9654626
TI  - Spinal surgery before and after Paul Harrington.

PMID- 9654627
TI  - Research: risks, benefits, and responsibilities. Presidential address.

PMID- 9654628
TI  - SRS travelling fellowship.
AB  - A 3-week tour of the Far East was coordinated by Dr. Ronald DeWald, senior
      travelling fellow appointed by the Scoliosis Research Society. Three junior
      fellows appointed by the Education Committee of the Scoliosis Research Society
      accompanied him. The purpose of this fellowship was to develop a comaraderie and
      exchange ideas, thoughts, and experiences in the field of spinal deformity.

PMID- 9654629
TI  - Revision pedicle screws. Bigger, longer shims--what is best?
AB  - STUDY DESIGN: To evaluate the effect of change in screw dimensions and hole
      augmentation in pedicle screw revisions, the insertional torque was determined,
      and results were compared with those in control specimens in an in vitro study
      using cadaveric thoracolumbar spines. OBJECTIVES: To determine the best method of
      salvage for failed pedicle screws, by evaluating the insertional torque after
      placing a larger diameter or longer screw into a stripped hole. Use of a shim and
      use of larger and longer screws were also investigated. Finally, the effect on
      insertional torque of simply removing and replacing a pedicle screw in its
      original hole was investigated. SUMMARY OF BACKGROUND DATA: The effects of using
      bigger or longer screws and shims to salvage failed pedicles have been studied.
      The interaction between how much larger, how much longer, and inserting with or
      without shims, has not been well studied. Optimizing reinsertional torque through
      the use of bigger screws risks exceeding the pedicle capacity. Using longer
      screws risks violation of the anterior vertebral body, thereby placing the great
      vessels and viscera at risk. By knowing the relative contribution of increase in
      length and diameter, the surgeon can optimize the risk-benefit ratio. METHODS:
      Eight cadaveric spines from T10 to S1 were harvested. The specimens underwent
      radiographic screening and bone densitometry. A modified Latin square
      randomization was designed to evaluate the screw diameters and lengths. Each
      pedicle was its own control. A 35- x 6.5-mm screw was used as a control. Test
      screws were placed after pedicle screw hole failure was achieved and documented
      by stripping. For the test screws, the diameters were increased by 1 mm and 2 mm,
      the lengths were increased by 5 mm and 10 mm. Shims were added randomly. The peak
      insertional torque was measured for each control screw and test screw placement.
      In addition, during each screw placement, the screw was removed and replaced to
      determine the effect. RESULTS: Insertional torque, after the pedicle screw is
      removed and replaced in the same hole, was decreased by 34% (P < 0.000005).
      Increasing the diameter of the salvage screw by 2 mm caused the insertional
      torque to be increased by 8.4% of the original. Increasing the length of the
      screw did not improve the salvage screw insertional torque. There was an
      interaction effect for the 1-mm increase in diameter and the increase in length.
      At this diameter, increasing the length had a significant effect (P = 0.009) on
      the salvage torque. Using a shim created no improvement in salvage insertional
      torque (P = 0.77). There was a poor linear correlation between torque and bone
      mineral density (r = 0.18) in these osteoporotic specimens. CONCLUSIONS: Removing
      and replacing a pedicle screw in its original hole substantially decreases its
      mechanical fixation. For pedicle salvage, increasing the diameter causes the
      greatest restoration of strength. Shims had no effect in pedicle salvage in
      osteoporotic specimens.

PMID- 9654630
TI  - A logical coronal pattern classification of 2,000 consecutive idiopathic
      scoliosis cases based on the scoliosis research society-defined apical vertebra.
AB  - STUDY DESIGN: Two thousand consecutive idiopathic scoliosis records and
      radiographs were reviewed for coronal pattern typing and categorization, based on
      Scoliosis Research Society definitions of the apical vertebra. Apical frequency
      was determined for each of the patterns identified, and represents a database
      from a large series of cases for the already accepted Scoliosis Research Society
      definitions. OBJECTIVES: To identify and numerically pattern-type a large series
      of idiopathic coronal curves, for the basic purpose of written and oral
      communication. Some pattern types were not described previously. SUMMARY OF
      BACKGROUND DATA: Although spinal deformity must be considered three dimensional
      for treatment in 1998, no comprehensive, databased, and user friendly coronal or
      sagittal classification of idiopathic scoliosis has been reported. METHODS: Two
      thousand idiopathic curve patterns from charts and radiographs were reviewed and
      the coronal patterns categorized by the apical vertebra. The resulting
      classification was tested for inter- and intraobserver reliability by 12 spine
      surgeons and 6 orthopedic residents. Apical frequencies were determined for each
      pattern type. RESULTS: Twenty-one pattern categories were identified, and all
      were right or left mirror image patterns (except for a quadruple pattern) that
      permitted separation into 11 types. Incorporating the widely recognized five
      numbered King types mad pattern recognition simple. Interobserver reliability
      testing was 98.2%. The left single thoracic curve pattern was included in this
      classification because only 9 (20.4%) of 44 patients with left thoracic curves
      had intraspinal pathology. CONCLUSION: Two thousand consecutive idiopathic
      coronal curve patterns separated into eleven readily identifiable types, and
      incorporating the widely referenced five King types, makes recognition simple for
      purposes of identification and communication. Sagittal and 3D factors excluded
      from this classification are equally important in the process of treatment
      decisions. Apical frequency data determined in this study lends credence to
      Scoliosis Research Society definitions for idiopathic curve patterns.

PMID- 9654631
TI  - Somatosensory- and motor-evoked potential monitoring without a wake-up test
      during idiopathic scoliosis surgery. An accepted standard of care.
AB  - STUDY DESIGN: This was a retrospective study of 500 patients undergoing
      corrective surgery between 1987 and 1997 for spinal deformity caused by
      idiopathic scoliosis. OBJECTIVES: To report the sensitivity and specificity of
      somatosensory-evoked and neurogenic motor-evoked potentials monitoring and the
      requirements for an intraoperative wake-up test for all idiopathic scoliosis
      surgeries at a single institution. SUMMARY OF BACKGROUND DATA: Intraoperative
      monitoring is recommended for use during corrective spinal surgery. Accepted
      monitoring standards and requirements for an intraoperative wake-up test are
      still debated. METHODS: The study group consisted of 500 patients undergoing
      corrective surgery for idiopathic scoliosis between 1987 and 1997. All patients
      were monitored using somatosensory-evoked and neurogenic motor-evoked potential
      techniques, using a standard protocol developed at this institution. RESULTS: The
      false-positive rate (significant data change without postoperative neurologic
      deficit) was 0.014% (n = 7). The true-positive rate (degradation of data that met
      warning criteria, with a corresponding postoperative neurologic deficit) was
      0.004% (n = 2). No false-negative results (normal data during with a
      postoperative neurologic deficit) were seen. The sensitivity of combined
      somatosensory-evoked and neurogenic motor-evoked potential data in predicting
      neurologic status was 98.6%, and the specificity of normal data predicting normal
      findings in a neurologic examination was 100%. CONCLUSION: Combined somatosensory
      evoked and neurogenic motor-evoked potentials monitoring during idiopathic
      scoliosis surgery represents a standard of care that obviates the need for an
      intraoperative wake-up test when reliable data are obtained and maintained.

PMID- 9654632
TI  - Nutritional depletion in staged spinal reconstructive surgery. The effect of
      total parenteral nutrition.
AB  - STUDY DESIGN: A prospective randomized study evaluating nutritional depletion in
      spine surgery patients. OBJECTIVE: To determine whether use of total parenteral
      nutrition (TPN) in patients undergoing staged spinal reconstructive procedures
      could affect their nutritional parameters or decrease their complication rates.
      SUMMARY OF BACKGROUND DATA: Several studies have shown that nutritional depletion
      occurs after major spinal surgery and that patients undergoing staged spinal
      surgery may be at particular risk of nutritional loss and its complications.
      METHODS: Forty adult patients undergoing staged spinal reconstructive surgery
      were randomized as to whether they received TPN postoperatively. Nutritional
      parameters, including skin fold measurement and albumin, pre-albumin,
      transferrin, and total lymphocyte counts, were obtained pre-operatively and at
      regular intervals. RESULTS: Five patients did not complete the study, leaving 35
      patients for analysis. There was a significant decrease in incidence of albumin
      and pre-albumin depletion for the patients who did not receive TPN compared with
      those who did receive TPN (P < 0.025, P < 0.006, respectively). Patients with
      depleted albumin or pre-albumin counts were more likely to develop other
      postoperative infectious complications such as pneumonia or urinary tract
      infections (P < 0.035). There were no statistically significant differences in
      wound complications in this small patient study. There were no complications
      secondary to use of the TPN. CONCLUSIONS: For complex patients requiring staged
      anterior/posterior surgery, TPN appears to significantly lessen the decrease in
      nutritional parameters. Because depletion of nutritional parameters appears to
      correlate with an increased likelihood of perioperative infectious complications,
      use of TPN may result in a decrease of such complications in these patients.

PMID- 9654633
TI  - Modified luque instrumentation after myelomeningocele kyphectomy.
AB  - STUDY DESIGN: Treatment of congenital kyphosis in myelomeningocele is a difficult
      problem. Current thinking supports kyphectomy and postoperative internal
      fixation. OBJECTIVES: Since 1989, vertebral resection with modified Luque
      fixation has been the procedure of choice for correction of myelomeningocele
      kyphotic deformity at the author's institution. The study objective was to
      evaluate long-term results with this technique. SUMMARY OF BACKGROUND DATA: Most
      investigators agree that kyphotic deformity in myelomeningocele should be treated
      with vertebral resection. There is less uniform consensus about postoperative
      fixation. Reports in the literature support fixation with modified segmental
      instrumentation. METHODS: Sixteen patients, observed for an average of 57.2
      months (range, 36-94 months), underwent vertebral resection from the proximal
      aspect of the apical vertebra cephalad into the compensatory lordotic curve.
      Fixation was segmental instrumentation wired to the thoracic spine and anterior
      to the sacrum. RESULTS: The average blood loss was 1121 mL (range, 450-2580 mL).
      Kyphotic deformity averaged 111 degrees before surgery (range, 75-157 degrees),
      15 degrees after surgery (range, -18-36 degrees) and 20 degrees at latest follow
      up (range, -17-83 degrees). Loss of correction was 6 degrees (range, 0-27
      degrees). Postoperative immobilization was with a thoracolumbosacral orthosis for
      18 months. Complications occurring in 8 of the 16 patients were transient
      headache, superficial wound breakdown, supracondylar femur fractures, and one
      late infection secondary to skin breakdown that necessitated early rod removal,
      resulting in some loss of correction. CONCLUSIONS: Kyphectomy is an excellent
      method of correcting rigid kyphotic deformity in the patient with myelodysplasia.
      Segmental spinal instrumentation provided three distinct advantages: rigidity of
      the construct, greater correction of the deformity and low-profile
      instrumentation.

PMID- 9654635
TI  - Bracing of patients after fusion for degenerative problems of the lumbar spine-
      yes or no?
AB  - The majority of spine fusions currently performed are for degenerative
      conditions. Controversy exists regarding whether to routinely brace patients
      during the postoperative period. The benefits of a rigid orthosis have yet to be
      documented in a scientific study, and the cost of a custom-molded orthosis can be
      quite high. An extensive literature search reveals few articles dealing with the
      subject, and none with an adequate study design to convincingly support or refute
      the use of external braces. In addition to the questions of whether an external
      brace is effective, the mechanism of action also remains unclear. It has been
      difficult to document mechanical effectiveness, so perhaps the effect is
      psychologic. In addition, it is possible that some, not all, fusion patients may
      benefit from a brace--yet our ability to select such a patient is poor. As a
      result, we have solicited the views of two experienced surgeons on the topic. Dr.
      Connolly argues that an external orthosis is advisable in many cases; Dr. Grob
      feels that the rigidity of internal fixation should be adequate to obviate the
      need for external bracing.

PMID- 9654634
TI  - Scoliosis in total-body-involvement cerebral palsy. Analysis of surgical
      treatment and patient and caregiver satisfaction.
AB  - STUDY DESIGN: A nonrandomized descriptive case series. OBJECTIVES: To analyze the
      results of spinal fusion in patients with total-body-involvement cerebral palsy
      to determine early and late outcomes, including caregiver satisfaction. METHODS:
      Data from 79 to 100 patients with total-body-involvement spastic cerebral palsy
      who underwent posterior Luque instrumentation, or anterior spinal fusion, or
      both, were adequate to be included in the study. Functional status was evaluated
      by physical examination, and a personal interview was conducted with the patient,
      parents, and primary caregiver. RESULTS: Median follow-up was 4 years (range, 2
      14 years). Late progression of scoliosis (> 10 degrees), pelvic obliquity (> 5
      degrees), and decompensation (> 4cm ) were noted in more than 30% of the
      patients. More than 75% of patients with late progression were skeletally
      immature at the time of surgery and underwent a posterior procedure only. Twenty
      one percent of the patients required a revision procedure because of disease
      progression. Progression was not noted in any patient who underwent anterior
      fusion (with or without anterior instrumentation) plus posterior instrumentation
      from the upper thoracic spine to the pelvis. Eighty-five percent of parents or
      caregivers were very satisfied with the results of surgery and noted a beneficial
      impact of the patient's sitting ability, physical appearance, ease of care, and
      comfort. CONCLUSIONS: To avoid late progression of trunk deformity in skeletally
      immature patients, anterior spinal release and fusion combined with posterior
      segmental spinal instrumentation and fusion from the upper thoracic spine to the
      pelvis are recommended. Skeletally mature patients with good curve flexibility
      can be treated with posterior instrumentation and fusion only. Skeletally mature
      patients with large fixed curves benefit from an anterior-posterior procedure for
      better correction of the scoliosis and pelvis obliquity. Despite the surgical
      complexity and expected complications, the overall good surgical results and high
      patient and caregiver satisfaction confirm that corrective spinal surgery is
      indicated and is beneficial for most patients with total-body-involvement
      cerebral palsy and scoliosis.

PMID- 9654636
TI  - The statistics of smoking.

PMID- 9654637
TI  - Uncovering the effects of smoking: historical perspective.
AB  - Tobacco was introduced into Europe from America at the end of the fifteen
      century. At first used primarily for medicinal purposes it came to be burnt in
      pipes for pleasure on a large scale nearly 100 years later, at first in England
      and subsequently in Europe and throughout the world. Pipe smoking gave way to the
      use of tobacco as snuff and, in turn, to cigars and cigarettes at different times
      in different countries until cigarette smoking became the dominant form in most
      of the developed world between the two world wars. Societies were formed to
      discourage smoking at the beginning of the century in several countries, but they
      had little success except in Germany where they were officially supported by the
      government after the Nazis seized power. In retrospect it can now be seen that
      medical evidence of the harm done by smoking has been accumulating for 200 years,
      at first in relation to cancers of the lip and mouth, and then in relation to
      vascular disease and cancer of the lung. The evidence was generally ignored until
      five case-control studies relating smoking to the development of lung cancer were
      published in 1950. These stimulated much research, including the conduct of
      cohort studies, which, by the late 1950s, were beginning to show that smoking was
      associated with the development of many other diseases as well. The
      interpretation that smoking caused these various diseases was vigorously debated
      for some years but came to be generally accepted in respect of lung cancer by the
      late 1950s and of many other diseases in the subsequent two decades. Cigarette
      smoking has now been found to be positively associated with nearly 40 diseases or
      causes of death and to be negatively associated with eight or nine more. In some
      instances the positive associations are largely or wholly due to confounding, but
      the great majority have been shown to be causal in character. The few diseases
      negatively associated with smoking are for the most part rare or nonfatal and
      their impact on disease incidence and mortality as a result of smoking is less
      than 1% of the excess of other diseases that are caused by smoking. The most
      recent observations show that continued cigarette smoking throughout adult life
      doubles age-specific mortality rates, nearly trebling them in late middle age.
      All the diseases related to smoking that cause large numbers of deaths should now
      have been discovered, but further nonfatal diseases may remain to be revealed by
      cohort studies that are able to link individuals' morbidity data with their
      personal characteristics.

PMID- 9654638
TI  - Lung cancer and passive smoking.
AB  - The evidence from epidemiological studies, studies of biochemical markers of
      exposure and toxicological studies, confirm that there is a causal association
      between the risk of lung cancer and exposure to environmental tobacco smoke.
      Nonsmokers can inhale and metabolize carcinogens in tobacco smoke and other
      markers of environmental tobacco smoke inhalation (nicotine and cotinine) are
      raised in nonsmokers exposed to environmental tobacco smoke. In epidemiological
      studies of women who are lifelong nonsmokers, there is a statistically
      significant excess risk of lung cancer (24%, 95% confidence interval 13-36%) from
      exposure to environmental tobacco smoke from the spouse and this increases with
      the number of cigarettes smoked and duration of the marriage. Misclassification
      bias (women who smoke but claim to be lifelong nonsmokers) and dietary
      confounding are unlikely to explain the association; after adjustment for both,
      the risk of lung cancer from environmental tobacco smoke exposure was still
      statistically significant. In any event, their effects on the risk of lung cancer
      in the epidemiological studies are balanced out by allowing for background
      exposure to environmental tobacco smoke (that is, other than from the spouse) in
      the reference group; the excess risk after allowing for all three is an estimated
      26% (95% confidence interval 7-47%), similar to the adjusted figure of 24%. In
      Britain, about one in every six nonsmokers are exposed to tobacco smoke from
      smokers in the home. Passive smoking is an avoidable cause of mortality and
      morbidity. Prevention strategies to reduce the amount of cigarette smoking in
      public places should be part of public health policy.

PMID- 9654639
TI  - Difficulties in assessing the relationship between passive smoking and lung
      cancer.
AB  - Since 1981, numerous epidemiological studies have investigated the relationship
      between passive smoking and lung cancer in nonsmokers. The overall evidence,
      predominantly relating to women, indicates a weak association with the husband's
      smoking and many reviewers have concluded that this demonstrates a causal effect
      of exposure to environmental tobacco smoke (ETS). Interpreting weak associations
      is notoriously difficult, however, and this paper reviews problems specific to
      the ETS-lung cancer relationship. After describing how to select relevant studies
      and appropriate data, the methods for combining evidence together ('meta
      analysis') are discussed, and the need to investigate sources of heterogeneity is
      emphasized. Separate consideration is given to various forms of bias that may
      affect overall relative risk estimates, including misclassification of active
      smoking status, confounding, systematic case-control differences, recall bias,
      diagnostic bias and publication bias. Sections on dose-response, multiple ETS
      exposure sources and other issues follow. The problems are illustrated from the
      available literature. It is shown there is no significant association of lung
      cancer with workplace, childhood or social ETS exposure or with smoking by the
      wife. Though statistically significant, the association with husband's smoking is
      weak and heterogeneous and varies widely according to various study
      characteristics. The association is markedly weakened by the adjustment for
      smoking misclassification bias and is likely to be affected by confounding and
      other sources of bias. While the precise extent of all the biases remains
      unclear, it seems impossible to conclude with any certainty that ETS causes lung
      cancer.

PMID- 9654640
TI  - Statistical methods in genetic research on smoking.
AB  - A growing body of evidence suggests that genetic factors have an important
      influence on the onset and course of smoking. Here we review some of the
      statistical methods that have been used to test for genetic influences on smoking
      behaviour, with a particular focus on studies of large national twin samples. We
      show how many of the hypotheses that have been tested using a genetic model
      fitting approach have also been reformulated using logistic regression models
      that will be more familiar to epidemiologists. Such an approach is more easily
      extended to allow for sociocultural, as well as genetic, influences on smoking
      behaviour. Using either approach, data are consistent in indicating that
      certainly in men, and possibly in women, genetic factors play an important role
      in predicting which individuals who become cigarette smokers progress to being
      long-term persistent smokers.

PMID- 9654641
TI  - Cigarette smoking prevalence, cessation and relapse.
AB  - This paper briefly reviews three aspects of cigarette smoking behaviour: recent
      British trends in prevalence and cessation, tobacco dependence and the nicotine
      withdrawal syndrome, and treatment for smokers using nicotine replacement
      therapy. It concludes with a meta-analysis of the effect of relapse in nicotine
      replacement trials. For many years, until 1994, smoking prevalence in the UK
      declined at a steady rate but since the early 1980s uptake in the young has
      remained high. This failure to curb recruitment in the young may be in part
      responsible for the recent rise in all-age smoking prevalence. Cessation rates
      are very low when compared with the proportion of smokers who wish to stop and
      repeatedly try to do so. This disparity can be attributed to the addictiveness of
      nicotine and the withdrawal symptoms which confront the would-be quitter. To
      date, the most effective adjunctive aid for smokers trying to quit is nicotine
      replacement therapy but even when abstinence for several months has been achieved
      the risk of relapse remains high.

PMID- 9654642
TI  - Steroids, gene expression, and apoptosis: recollections of contributions and
      controversies.

PMID- 9654643
TI  - Synthesis and stereochemistry of 8,13-diaza-2,3-dimethoxygona-1,3,5(10),9(11)
      tetraen-12-one and D-homo derivatives.
AB  - From the condensation reaction of O-methylbutyrolactim (2), O-methylvalerolactim
      (3), O-methylcaprolactim (4) and O-methyl-4-t-butylcaprolactim (5) with ethyl 6,7
      dimethoxy-alpha-[1-(1,2,3,4-tetrahydro-isoquinolyl)] acetate (1), 8,13-diaza-2,3
      dimethoxygona-1,3,5(10),9(11)-tetraen-1 2-one (6) D-homo-derivatives (7-9), and
      medium-sized ring cyclic diamides (10,11) were obtained. The stereoselective
      reduction of compounds 6-9 by Adam's platinum catalyst afforded 8,13-diaza-2,3
      dimethoxygona-1,3,5(10)-trien-12-one (12) and its D-homo derivatives (13-15). The
      structures of the compounds obtained were established by NMR and X-ray
      crystallographic analyses.

PMID- 9654644
TI  - Hydroxylation of pregnenolone at the 7 alpha- and 7 beta- positions by mouse
      liver microsomes. Effects of cytochrome p450 inhibitors and structure-specific
      inhibition by steroid hormones.
AB  - Hydroxylations of pregnenolone (PREG) at the 7 alpha-and 7 beta-positions have
      been reported in numerous murine tissues and organs, including liver, and the
      responsible cytochrome P450 (P450) species await identification. Using thin-layer
      chromatography and gas chromatography-mass spectrometry and crystallization to
      constant specific activity, we report identification of 7 alpha-hydroxy-PREG and
      7 beta-hydroxy-PREG metabolites produced in mouse liver microsomes and kinetic
      studies of their production with apparent KM values of 2.45 +/- 0.124 microM and
      3.41 +/- 0.236 microM for 7 alpha- and 7 beta-hydroxylation, respectively.
      Investigation of P450 inhibitors and of steroid hormone effects on both 7 alpha-
      and 7 beta-hydroxylation of PREG showed that 1) different P450 were involved
      because metyrapone and antipyrine inhibited solely 7 alpha-and 7 beta
      hydroxylation, respectively; 2) P450 1A2, 2D6, 2B1, and 2B11 were not responsible
      for 7 alpha and 7 beta-hydroxylation of PREG because respective specific
      inhibitors furafylline, quinidine, and chloramphenicol triggered no inhibition;
      3) P450 1A1 was responsible for only part of the 7 beta-hydroxylation of PREG
      because alpha-naphthoflavone, which inhibits specifically P450 1A1, did not
      suppress entirely 7 beta-hydroxylation while ketoconazole, antipyrine, and
      metyrapone extensively decreased the 7 beta-hydroxylation; 4) comparison of these
      findings with those obtained with brain microsomes suggests that tissue-specific
      P450 species are responsible for the 7 alpha-and 7 beta-hydroxylation of PREG;
      and 5) 7 alpha-hydroxylation of PREG may be shared with other 3 beta
      hydroxysteroids such as isoandrosterone, 5-androstene-3 beta, 17 beta-diol, and
      dehydroepiandrosterone, which acted in a competitive manner. Taken together,
      these findings will be of use for identification of the P450 species responsible
      for 7 alpha- and 7 beta-hydroxylation of PREG and for studies of their activities
      in liver and other organs.

PMID- 9654645
TI  - Studies on the hydrogenation of the progestagen dienogest in vivo and in vitro in
      the female rabbit.
AB  - The biotransformation of the progestagen dienogest (17 alpha-cyanomethyl-17 beta
      hydroxy-4,9-estradien-3-one) was studied in vivo in female rabbits and in vitro
      by liver homogenates from female rabbits and rats. In vivo, in the female rabbit,
      3H-dienogest was the subject of an extensive biotransformation. A significant
      difference between the composition of the urinary and biliary metabolite patterns
      of dienogest was found. While in the urinary metabolite pattern more polar
      metabolites dominated, in bile of animals with a bile fistula, a dienogest
      metabolite of medium polarity was prevalent. This main metabolite of dienogest
      was identified by MS, 1H- and 13C-NMR spectroscopy and CD measurement of an
      enzymatic dehydrogenation product as the tetrahydro metabolite 17 alpha
      cyanomethyl-5 alpha-estr-9-en-3 beta,17 beta-diol. Thus, in vivo, the 4,9-dien-3
      oxo-19-norsteroid dienogest is hydrogenated to a 5 alpha H-9-en metabolite. In
      vitro, however, 3H-dienogest was only poorly transformed by liver homogenates
      from both species, whereas 3H-levonorgestrel and 3H-3-keto-desogestrel were
      converted partially by liver homogenates from female rabbits and completely by
      liver homogenates from female rats. The principal biotransformation reactions of
      levonorgestrel and 3-ketodesogestrel were the reduction of the 3-oxo group to 3
      OH and the 5 beta- and 5 alpha-hydrogenation of the 4-double bond by homogenates
      of female rabbit liver and female rat liver, respectively. A dihydro metabolite
      of dienogest, in which the 3-oxo group had been reduced to 3-OH, was isolated in
      small amounts from the incubation with rabbit liver homogenate. The data indicate
      that the enzymatic hydrogenation of the 4-double bond of the 4,9-dien-3-oxo
      steroid dienogest is inhibited in vitro. The hindered hydrogenation reaction in
      vitro has to be seen in association with the 9-double bond in the steroid
      molecule.

PMID- 9654646
TI  - Effect of sodium restriction on urinary excretion of cortisol and its metabolites
      in humans.
AB  - The adrenal gland is involved in the control of urinary sodium excretion mainly
      via the secretion of the mineralocorticoid aldosterone. Although under certain
      conditions glucocorticoid seem to be also involved in the regulation of sodium
      homeostasis, there are contradictory reports on the relationship between cortisol
      secretion and sodium intake. Given recent findings linking regulation of
      physiological activity of steroids to the activity of specific enzymatic
      pathways, we have examined changes in urinary excretion of cortisol and its
      metabolites in eight healthy volunteers on a low sodium diet. Urinary steroids
      were measured with specific radioimmunoassays after extraction and chromatography
      (F and E) or after dilution (THF and THE). Excretion of cortisol (124 +/-41
      nmol/day) was significantly lower on Day 2 (86 +/- 27 nmol/day, p < 0.01) and Day
      7 (85 +/- 25 nmol/day, p < 0.01) of sodium restriction. On the same samples
      calculated ratios of THF/F (55 +/- 15; 61 +/- 22; 68 +/- 21) and E/F (2.5 +/-
      0.6; 2.8 +/- 1.4; 3.0 +/- 1.3) reflecting the activity of 5 beta-reductase and 11
      beta-hydroxysteroid dehydrogenase, respectively, showed significant increases in
      the former on both Days 2 and 7 and for the latter only on Day 7. This study
      supports the notion that sodium restriction decreases urinary cortisol excretion
      and provides evidence that increased activity of 5 beta-reductase and lowered
      metabolism by 11 beta-HSD are presumably the mechanisms of this decrease.

PMID- 9654647
TI  - Application of an improved ELISA assay to the analysis of urinary estrogen
      metabolites.
AB  - Work from Strang and other laboratories has established that the 2-/16 alpha
      hydroxyestrone ratio is inversely correlated with the risk for breast and
      cervical cancer. In order to measure these metabolites in urine samples, it is
      essential to have an assay for these compounds that is both sensitive and
      reproducible. The present paper describes such an ELISA assay, which overcomes
      problems that existed in prior approaches to measuring these compounds. The new
      ELISA procedure supplies greater sensitivity and reproducibility than earlier
      assay procedures. The ELISA assay has also been found to correlate well with the
      GC-MS procedure of Adlercreutz.

PMID- 9654648
TI  - Effect of long-term treatment with aromatase inhibitor on testicular function of
      adult male bonnet monkeys (M. radiata).
AB  - The role/need for estrogen in regulating testicular function of adult male bonnet
      monkeys (M. radiata) has been investigated by dosing orally a group of five
      normal males 2.5 mgs of CGP 47645, a long-acting nonsteroidal aromatase inhibitor
      (AI), once every 5 days for over 150 days. Such treatment resulted in a 10-fold
      increment in nocturnal serum testosterone (T) levels, which were sustained for 85
      days of treatment, and a twofold increment in basal serum T levels was present
      throughout the 150 days of treatment. Analysis of ejaculated semen showed a
      marked reduction (approximately 90%) in sperm counts in four out of five monkeys
      between Days 55-85 of treatment. During this period, the motility score also was
      markedly reduced from a normal score of 3-5 to 0-2. Flow cytometric analysis of
      testicular germ cells obtained from biopsy tissue taken on Days 63 and 120
      indicated a marked reduction only in elongating/elongated spermatid population
      (compared to Day 0 values), suggesting inhibition in spermiogenic process.
      Epididymal sperm maturation also seemed effected as sperm chromatin, on flow
      cytometric analysis for decondensability following exposure to 5 mM
      dithiotreitol, showed to be in a hypercondensed state. This study thus indicates
      that estrogen has an important role in providing normal testicular and sperm
      function in the primate.

PMID- 9654649
TI  - Ginsenoside Rg1 down-regulates glucocorticoid receptor and displays synergistic
      effects with cAMP.
AB  - Ginsenoside-Rg1 (G-Rg1) from the roots of Panax ginseng C. A. Meyer has been
      shown to bind to the glucocorticoid receptor (GR). To further explore the effect
      of G-Rg1 binding to GR, a luciferase reporter gene containing two copies of a
      glucocorticoid response element was constructed and transiently transfected into
      FTO2B rat hepatoma cells. A dose-dependent induction of the reporter gene was
      observed in response to G-Rg1, and the inductive effect was blocked by treatment
      with the antiglucocorticoid RU486. In addition, both G-Rg1- and dexamethasone
      (Dex)-induced transcription was synergistically enhanced by the treatment of
      dibutyryl cAMP (Bt2-cAMP). G-Rg1 treatment also led to the down-regulation of
      intracellular GR content, which was similar to the effect of Dex. By showing that
      G-Rg1 down-regulates GR and induces GR-mediated transcription synergistically
      with cAMP, we conclude that G-Rg1 is a functional GR ligand in FTO2B cells.

PMID- 9654650
TI  - Development of potent non-estrogenic estrone sulfatase inhibitors.
AB  - Estrogen levels in breast tumors of post-menopausal women are as much as 10 times
      higher than estrogen levels in plasma, presumably due to in situ formation of
      estrogen. The major source of estrogen in breast cancer cells may be conversion
      of estrone sulfate to estrone by the enzyme estrone sulfatase. Thus, inhibitors
      of estrone sulfatase have potential for the treatment of estrogen-dependent
      breast cancers. Several steroidal agents have been developed that are potent
      estrone sulfatase inhibitors, most notably estrone-3-O-sulfamate. These compounds
      may have undesired actions, especially estrogenicity. Recently, non-steroidal
      estrone sulfatase inhibitors have been designed that avoid the problems
      associated with an active steroid nucleus; however, these have not achieved the
      potency of estrone-3-O sulfamate. We have designed and synthesized a series of
      compounds, 17 beta-(N-alkylcarbamoyl)-estra-1,3,5(10)-trien-3-O-sulfamates (6a-d)
      and 17 beta-(N-alkanoyl)-estra-1,3,5(10)-trien-3-O-sulfamates (11a-d) that
      combine the structural features of the steroidal estrone sulfatase inhibitors
      with a membrane insertion region that should increase the affinity for the
      sulfatase enzyme and decrease the estrogenicity of the steroid. We tested the
      compounds for estrone sulfatase inhibition by measuring estrone sulfatase
      activity in intact cultures of human breast cancer cells (MDA-MB-231). We tested
      for estrogenicity by measuring growth of estrogen-dependent MCF-7 human breast
      cancer cells. All of the test compounds (10 nM) substantially inhibited estrogen
      sulfatase activity of intact MDA-MB-231 cells. Dose-response analysis indicated
      an IC50 of approximately 0.5 nM for two of the compounds (6a and 11a). In the
      test for estrogenicity, estrone and estrone-3-O-sulfamate significantly
      stimulated MCF-7 cell growth. In contrast, neither the 17 beta-(N-alkylcarbamoyl)
      estra-1,3,5,(10)-trien-3-O-sulfamates++ + nor the 17 beta-(N)-alkanoyl)-estra
      1,3,5,(10)-trien-3-O-sulfamates stimulated growth of MCF-7 cells at a
      concentration of 1 microM, indicating that they are not estrogenic at levels 2000
      times greater than their IC50 for estrone sulfatase. Our data indicate the
      utility of the new compounds for inhibition of breast cancer cell estrone
      sulfatase activity. Further, our data support the concept that estrone sulfatase
      inhibitors may be useful as therapeutic agents for estrogen-dependent breast
      cancers.

PMID- 9654651
TI  - Estrogenic effects of the synthetic aminoestrogen 17 beta-(5-hydroxy-1
      pentylamino)-1,3,5(10)-estratrien-3-ol (pentolame).
AB  - In this study, we investigated the effects of pentolame, a 17 beta-aminoestrogen
      derivative, upon coagulation, serum LH, pituitary progestin receptors, uterine
      weight, and endometrium morphological changes in the castrated female rat. Groups
      of animals were subcutaneously (s.c.) injected with either estradiol (E2) (0.1 up
      to 1000 micrograms/animal), pentolame (1 up to 1000 micrograms/animal), or the
      vehicle alone daily for 5 consecutive days starting 2 weeks following
      ovariectomy. Administration of pentolame (10 to 1000 micrograms/animal) increased
      significantly (p < 0.05) the blood clotting time when compared with that obtained
      in the group of control animals (EC50 582 micrograms). Pentolame (500 and 1000
      micrograms/rat for 5 days) caused a significant inhibition (p < 0.01) of serum LH
      levels (IC50 860 micrograms), which remained suppressed until Day 5 post last
      injection. In addition, treatment with pentolame was able to restore in the
      castrated female rat the presence of specific estrogen-dependent progestin
      binding sites at the anterior pituitary level. The affinity constants and the
      number of binding sites of pentolame-induced progestin receptors were similar to
      those obtained with estradiol at equipotent doses (860 micrograms vs. 1
      microgram/animal, respectively). Administration of the 17 beta-aminoestrogen
      derivative resulted in a significant increase in uterine weight (EC50 420
      micrograms) and endometrial characteristics were indistinguishable from those
      observed in the group of rats treated with E2.

PMID- 9654652
TI  - A little heart trouble. Mary Lasker and the founding of the National Heart
      Institute.

PMID- 9654653
TI  - Open hearts. The origins of direct-vision intracardiac surgery.
AB  - Only 50 years ago, operating under direct vision within the walls of the living
      human heart appeared to be a surgical problem with no great hope of solution.
      However, technologic advances soon provided the necessary tools, and a safe,
      reliable, and practical technique of performing surgery within the open heart
      evolved in a series of stages. First, W.G. Bigelow espoused applied hypothermia
      as a means of protecting the vital organs during direct cardiac repair--a
      technique that F.J. Lewis then applied in correcting an atrial septal defect
      under direct vision. This was followed by C.W. Lillehei's introduction and
      application of controlled cross-circulation, which enabled the correction of more
      complex cardiac lesions. Finally, the efforts of J.H. Gibbon and J.W. Kirklin led
      to the creation of a reliable cardiopulmonary bypass apparatus, which enabled the
      many subsequent achievements well recognized in the history of surgery.

PMID- 9654654
TI  - New findings on the origin of the blood supply to the atrioventricular node.
      Clinical and surgical significance.
AB  - The anatomy of the heart's conduction system and of its blood supply have been
      research topics for many years. However, several proposals have never been
      demonstrated. In this paper, we describe 2 vascular conduits that have never
      before been objectively shown to supply the conduction system. Twenty human
      hearts from subjects aged between 15 and 65 years--with and without coronary
      disease--were dissected after anterograde and retrograde injection with latex
      butaclor E-650 by means of a technique developed by the authors. In 40% of these
      hearts, Kugel's artery was found to supply the atrioventricular node. The right
      descending superior artery supplied the atrioventricular node in 70% of the
      hearts dissected. These findings may be of major significance both in clinical
      cardiology and in cardiovascular surgery.

PMID- 9654655
TI  - Repair of stenotic saphenous vein grafts in infrainguinal arterial
      reconstructions.
AB  - We describe a technique of repairing autologous vein grafts affected by segmental
      stenosis. This technique can be of value both in reoperating on an old saphenous
      vein graft implanted for infrainguinal limb revascularization and in harvesting
      fresh saphenous vein in which an unexpected short-segment stenosis has been
      encountered.

PMID- 9654656
TI  - A no-touch technique for calcified ascending aorta during coronary artery
      surgery.
AB  - Despite improvements in cardiovascular surgery techniques over the years, the
      incidence of neurologic complications has not declined, and stroke remains a
      possible (and devastating) sequela to coronary artery surgery. In this report, we
      describe a moderate hypothermic fibrillatory arrest technique that avoids cross
      clamping or otherwise touching the aorta; use of the internal thoracic arteries
      and the right gastroepiploic artery provides optimum revascularization and
      minimizes the risk of cerebrovascular accident. Over a 1-year period, we used the
      technique in 21 patients who had heavy calcifications of the ascending aorta. No
      hemodynamic problems, lower-limb ischemia, or neurologic complications were seen.
      Only 1 patient underwent reoperation (for bleeding), and another--whose
      revascularization was incomplete--had a high postoperative level of myocardial
      creatine kinase MB isoenzyme and a new Q wave, but no hemodynamic deterioration.
      This technique seems reasonable, because it appears to provide good myocardial
      protection and to reduce neurologic complications, without comprising myocardial
      revascularization.

PMID- 9654657
TI  - Coronary artery bypass grafting in patients with profound ventricular
      dysfunction.
AB  - Patients with severe ventricular dysfunction make up a special subset of patients
      who undergo coronary artery bypass procedures. For these patients, the risk
      associated with the bypass procedure is relatively high, but the opportunity-for
      survival benefit is also greater. We studied 61 consecutive coronary artery
      bypass patients with preoperative ejection fractions < or = 25%, and further
      compared several subgroups: Group I (n = 30) ejection fractions ranged from 21%
      to 25%; Group II (n = 23) ejection fractions ranged from 16% to 20.9%; and Group
      III (n = 8) ejection fractions ranged from 10% to 15.9%. The overall mortality
      rate was 8% (5/61), with no deaths in Group III. The 41% (25/61) of patients who
      received left internal mammary artery conduits experienced a higher mortality
      rate, yet it did not differ significantly from that of patients who received only
      saphenous vein conduits. Intraaortic balloon pumps were placed in 48% (29/61) of
      the patients, with a progressively higher incidence in patients with poorer
      ventricular function (P < 0.05). Most intraaortic balloon pumps (59%) were placed
      intraoperatively. Two patients underwent placement of left ventricular assist
      devices, and 1 of these survived. Coronary artery bypass grafting in patients
      with poor ventricular function carries a substantial, but acceptable, mortality
      risk. Use of the left internal mammary artery did not improve perioperative
      mortality, and may have a negative impact in the early postoperative period.
      Intraaortic balloon pump use was most common in those patients with the worst
      ventricular function. Prophylactic intraaortic balloon pump use may be justified
      in candidates with ejection fractions < 20%.

PMID- 9654658
TI  - Thrombolytics and left-sided prosthetic valve thrombosis. A case report.
AB  - Prosthetic valve thrombosis is a well-known condition. Because surgical treatment
      of prosthetic valve thrombosis is associated with a high mortality rate, the use
      of thrombolysis as therapy for this condition has gained popularity in recent
      years. In this article, we discuss the cases of 3 patients who presented to our
      institution with left-sided prosthetic valve thrombosis between 1994 and 1997.
      All 3 patients presented with New York Heart Association functional class III or
      IV symptoms, and all were successfully treated with urokinase. The use of
      thrombolytic therapy for left-sided prosthetic valve thrombosis is associated
      with low mortality rates, and therefore is an attractive alternative to valve
      replacement or thrombectomy. However, the risk of embolic and hemorrhagic
      complications precludes the use of thrombolysis in patients with large thrombi
      and in those with New York Heart Association functional class I and II symptoms;
      for these patients, the risk associated with thrombolysis exceeds surgical
      mortality rates.

PMID- 9654659
TI  - Mycotic aneurysm of the popliteal artery secondary to tuberculosis. A case report
      and review of the literature.
AB  - Mycotic aneurysms of the popliteal artery are rare; 33 cases have been reported
      in the literature. The treatment of choice is a large excision with extra
      anatomic revascularization. In situ revascularization is sometimes possible. To
      the best of our knowledge, tuberculosis has never been reported as a causal
      factor of mycotic aneurysms of the popliteal artery. We report a case of a
      recurrent tuberculous false aneurysm of the popliteal artery. After 2 attempts at
      in situ revascularization, the femoral artery was ligated with no distal
      ischemia.

PMID- 9654660
TI  - Is nitroglycerin detrimental in patients with coronary artery ectasia? A case
      report.
AB  - During the management of acute myocardial infarction, we observed that clinical
      and electrocardiographic indications of myocardial ischemia worsened upon
      nitroglycerin infusion and were promptly relieved upon streptokinase infusion.
      Subsequent coronary angiography revealed diffuse ectasia with no significant
      stenosis. We discuss the possible pathophysiologic mechanisms by which
      nitroglycerin might exacerbate ischemia in patients with non-stenotic ectasia,
      and we present supporting data from other sources. We also attempt to identify
      the characteristics of patients whose acute myocardial ischemia might be worsened
      by the administration of nitroglycerin.

PMID- 9654661
TI  - Improvement of reversible ischemia in severe post-transplantation coronary artery
      disease.
AB  - Coronary artery disease is a major cause of morbidity and mortality in patients
      who have undergone heart transplantation. Patients are often asymptomatic during
      the onset of the disease, and managing the disease is difficult. This report
      describes the case of a patient with post-transplantation coronary artery disease
      who, despite the severe, progressive appearance of the disease on angiographic
      examination, showed evidence of autorevascularization and collateralization.

PMID- 9654662
TI  - Spongy left ventricular myocardium in an adult.
AB  - "Spongy left ventricular myocardium," or noncompaction of left ventricular
      myocardium, is a rare disorder of endomyocardial morphogenesis. It is usually
      seen in the pediatric population and is often associated with other congenital
      cardiac malformations. We describe an adult with noncompaction of left
      ventricular myocardium without associated congenital cardiac anomalies.

PMID- 9654663
TI  - Symptomatic lipoma in the right atrial free wall. A case report.
AB  - Benign non-myxomatous neoplasms of the heart are rare, and lipomas are among
      those least often encountered. We report the case of a 38-year-old man who
      presented with palpitations of recent onset, and was found to have a lipoma
      attached to the free wall of the right atrium. The successful surgical excision
      of the lipoma is described.

PMID- 9654664
TI  - Polymorphic regurgitation jets in a flail mitral valve.

PMID- 9654665
TI  - Transcatheter alcohol ablation of the septum in hypertrophic cardiomyopathy.

PMID- 9654666
TI  - Persistent left superior vena cava.

PMID- 9654667
TI  - [Early days and path of thoracic ultrasound].

PMID- 9654669
TI  - [Effects of extracorporeal ultrasound shockwaves on the relatively mature embryos
      of the teleost Oryzias latipes].
AB  - Exposure to low-energy ultrasound shock waves (1000 impulses at a frequency of
      2/sec and an energy density of 0.08 mj/mm2; peak positive/negative pressure 16/-7
      MPa; pulse duration about 10 musec) led to the following alterations in the cells
      and tissues of stage 35 embryos of Oryzias latipes ranked according to their
      extent: (1) In various tissues, especially in the trunk musculature, orthodox
      mitochondria were transformed into condensed (= low energy) mitochondria. (2)
      Nuclear envelopes and sarcoplasmatic reticulum of muscle fibres as well as
      endoplasmatic reticulum of epidermal ionocytes were often vesicularly dilated.
      (3) Muscle fibres in the trunk musculature began to separate from each other.
      Epidermal intercellular spaces were enlarged and increased in number. (4)
      Destruction of vessels and haematomas were observed in the circulatory system of
      the yolk sac. (5) Necroses up to total disintegration were found in various
      organs of the body cavity (intestine, liver, spleen). The less serious
      alterations (1 and 2) occurred in organs completely surrounded by other tissues.
      Major damages (4 and 5), however, affected only organs with free outer and inner
      surfaces, probably explained by cavitation and jet stream phenomena within the
      adjacent fluids.

PMID- 9654670
TI  - [Ultrasound-controlled interstitial high frequency thermotherapy (HFTT)--in vitro
      studies of the bovine liver].
AB  - PURPOSE: Sonographically-guided Radio-Frequency Tissue Ablation-applied with a
      percutaneously placed needle can be used for the palliative treatment of primary
      or secondary liver tumours. In vitro experiments were carried out to establish
      the relations of the coagulation zone to histologic findings and sonographic
      appearance. METHOD: Fresh bovine livers were obtained and radio-frequency was
      applied under ultrasound guidance. The coagulation zone was dissected and
      examined by determining its three-dimensional diameters (macroscopically) and the
      histologic appearance of the coagulation margin to the surrounding tissue. In our
      series of 50 experiments the application time ranged from 30 seconds to 10
      minutes. RESULTS: The coagulation zone increased with increasing application time
      in a way that can be described as a negative logarithmic function. The largest
      volume was 4 x 5 x 5 cm (length, width, depth) approximating 50 ml. It was no
      problem to judge the coagulation zone sonographically. The macroscopically and
      sonographically determined width and length correlated with coefficients of 0.90
      and 0.96. Microscopically the coagulation necrosis showed sharply outlined
      margins without any vital cells. CONCLUSION: Radio-Frequency Tissue Ablation
      applied under sonographic guidance has certain features which seem to make it a
      promising method for the palliative treatment of primary and secondary tumours of
      the liver.

PMID- 9654671
TI  - [Ultrasound hip joint screening in newborn infants. Is twin pregnancy a risk
      factor for dysplasia?].
AB  - PURPOSE: This study aimed at investigating whether twin pregnancy is a risk
      factor for congenital dysplasia of the hip. METHOD: From 1987 until 1994 the hips
      of 3739 (1902 male, 1837 female) newborn were examined by ultrasound (screening)
      according to Graf's technique. We compared the results of twins and the other
      newborn (non-twins). The examinations were performed by 19 physicians. 73 (2%) of
      the newborn were twins (29 male, 44 female). RESULTS: In the group of 3666 non
      twins we found the types of hip IIa (alpha < 55 degrees) to IV (Graf's
      classification) in 237 (6.5%) newborn: 136 (3.7%) right side/183 (5.0%) left
      side. Only 2 (2.7%) of the 73 twins showed these types of hip. We found 4%
      (149/3739) breech presentations at birth in the entire group. 3.9% (141/3666) in
      the group of non-twins and 11% (8/73) cases in the twin group. 5.2% (190/3666) of
      the non-twins and 2.7% (2/73) of the twins required a treatment with abduction
      orthosis or Pavlik harness. CONCLUSION: This report shows that the types of hip
      IIa (alpha < 55 degrees); IIc; D; IIa, IIb and IV according to Graf and a
      required treatment in twins was significantly not more frequent than in the other
      newborn (non-twins), although twins showed more often a breech presentation at
      birth. The different kind of breech position in twins (hips and knees in flexion,
      legs and feet parallel) and non-twins (hips in flexion, knees in extension) could
      be one reason for these results. Besides, non-twins assume their breech position
      earlier than twins with a consecutively longer period of time of mechanical
      stress on the hips.

PMID- 9654672
TI  - [Preoperative axilla sonography in breast tumor suspected of malignancy--a
      diagnostic advantage?].
AB  - PURPOSE: To assess the value of preoperative axillary sonography possibly
      malignant for breast tumours. METHOD: We performed preoperative axillary
      sonography on 89 patients with suspicious breast tumours. In 78 cases, among
      which there were 74 invasive carcinomas, the surgery that followed included an
      axillary lymph node dissection and a comparison with the histology was possible.
      RESULTS: The sonographic detection of axillary lymph node metastases has a
      sensitivity of 90% and a specificity of 91.7% in relation to all tumour stages
      and a sensitivity of 100% and specificity of 89.6% in relation to T1 tumours. In
      our analysis, therefore, it is vastly superior to a clinical examination of the
      axilla. CONCLUSION: Ultrasonography is an accurate imaging method for the
      diagnosis of axillary lymph node metastases. Broadening this analysis to include
      more patients will validate this conclusion. The results of our preliminary study
      suggest that this diagnostic method could help reduce unnecessary radical surgery
      in the treatment of breast cancer.

PMID- 9654673
TI  - Lung sonographic findings in patients with suspected pulmonary embolism.
AB  - PURPOSE: To assess the feasibility and diagnostic performance of lung
      transthoracic sonography in patients with suspected pulmonary embolism. METHOD:
      In a prospective clinical study we compared sonographic findings of the
      peripheral lung with various scintigraphic gradings and D-dimer plasma
      concentrations. One hundred and nineteen consecutive patients with clinical signs
      of pulmonary embolism were investigated within 24 hours of the onset of symptoms.
      RESULTS: Seventy patients with suspected pulmonary embolism (59%) had sonographic
      lesions, which were echo poor, homogeneous and rounded or wedge-shaped with a
      hyperechoic reflexion in the centre. Of the patients with high-probability
      scintigraphic scans 86% had such sonographic lesions as had 79% with
      intermediate, 64% with low-probability and 33% with normal scintigraphic scans.
      Of the patients with positive sonographic findings and normal or low-probability
      scans only a minority (14%) had negative D-dimer tests. CONCLUSION: We found a
      high rate of specific sonographic lesions in patients with suspected pulmonary
      embolism when investigating the peripheral lung with ultrasound.

PMID- 9654674
TI  - [Optimizing antrum planimetry for ultrasound determination of gastric emptying
      using emptying function reference lines].
AB  - Previous studies have shown high inter- and intraindividual variation
      coefficients (Vkinter; Vkintra) of the gastric emptying time t(end) determined by
      sonographical antrum planimetry. PURPOSE: Are there new parameters reflecting the
      functional process of gastric emptying? METHOD: Gastric emptying of 300 ml water
      was studied in 20 healthy volunteers by sonographical antrum planimetry. 10
      volunteers were examined a second time on another day. RESULTS: High variation
      coefficients Vkinter (42%) and Vkintra (31%) could be demonstrated. Moreover, a
      correlation of r = +0.922 between tend and the maximal percentual increase of the
      antral area was evident. This relation is introduced as the functional-emptying
      line (FEL). CONCLUSION: Using the functional aspects of FEL, gastric emptying can
      be studied sonographically under functional aspects.

PMID- 9654675
TI  - [Mucinous cystadenoma of the appendix].
AB  - A 63-year old female patient was admitted with a unclear abdominal ultrasound
      scan. Despite all our diagnostic examinations, the diagnosis--mucinous
      cystadenoma--was first established during surgery by intraoperative histological
      evaluation. We discuss the diagnostic possibilities and therapeutic approach.

PMID- 9654676
TI  - Sonographic appearance of an appendix carcinoma.
AB  - Malignant appendix tumours are rare entities. Especially adenocarcinomas, which
      only appear in about 10% of appendix tumours, are very seldom. Preoperative
      diagnosis is very difficult due to a lack of typical clinical signs and a
      clinical appearance mimicking perforated appendicitis. Nevertheless, sonography
      is able to show indirect signs and therefore it can provide the surgeon with more
      information for a better operative treatment.

PMID- 9654677
TI  - [EFSUMB tutorial: thermal and mechanical indices].

PMID- 9654678
TI  - HSV molecular biology: general aspects of herpes simplex virus molecular biology.
AB  - Comparison of the herpes simplex virus type 1 (HSV-1) DNA sequence with that of
      other alpha, beta and gamma-herpesviruses, allied with molecular genetic studies
      have greatly increased understanding of the HSV genome and the functions encoded
      by individual virus genes and has facilitated the development of rational
      antiviral strategies. Here we review the coding content of the HSV-1 genome and
      identify: genes encoding structural components of the capsid, tegument or
      envelope; genes whose products are essential for growth in tissue culture; and
      genes that are conserved between members of the alpha, beta and gamma
      herpesvirinae. The HSV lifecycle and the main regulation cascade is discussed and
      genes that present targets for antiviral intervention identified. The protein
      content of the infectious virion particle is reviewed and compared with that of
      two additional non-infectious HSV-related particles species (L-particles and pre
      DNA replication particles (PREPs)). The potential of HSV-1 L particles and PREP
      particles as DNA-free HSV-1 vaccine candidates and the desirability of deleting
      specific gene products from live HSV vaccines is discussed.

PMID- 9654679
TI  - Methods for the detection of non-random base substitution in virus genes: models
      of synonymous nucleotide substitution in picornavirus genes.
AB  - A substantial fraction of phylogenetic divergence between closely related RNA
      virus genes is generally accounted for by synonymous (non-amino acid changing)
      point mutation. Viral evolution may be a complicated phenomena, governed by many
      different processes. However in this study we ask whether there are any
      properties in the patterns of synonymous nucleotide substitutions in three
      different Picornavirus genes that permit the process of accumulation of
      synonymous point mutation in these genes to be distinguished from some of the
      simplest most basic evolutionary models. We conclude that while the observed
      patterns in the occurrence of synonymous point substitution are consistent with
      those predicted by a model in which base mutation is equi-probable along a gene,
      and the probability of synonymous substitution determined only by local codon
      usage, some patterns in the actual nucleotides exchanged remain to be explained.

PMID- 9654680
TI  - Transcription analysis of porcine circovirus (PCV).
AB  - This study focuses on gene expression of porcine circovirus (PCV) in order to
      identify viral genes and their corresponding mRNA transcripts. By northern blot
      analysis, the existence of three mRNAs could be demonstrated. Two mRNAs are
      encoded by the viral (-)-strand and one is encoded by the viral (+)-strand. The
      (+)-strand encoded mRNA transcript is 990 nucleotides (nt) long and corresponds
      to the open reading frame (ORF) 1, as shown by S1 mapping. The start point of
      this transcript is located at pos. 1238, as determined by primer extension
      analysis and rapid amplification of cDNA ends (RACE). The transcript is spliced
      as shown by direct reverse sequencing and RACE. It contains an untranslated
      "leader"-sequence 119 nt in size (pos. 1238 to 1120) which is joined to exon 2 of
      the ORF 1 transcript at pos. 737. The transcriptional regulatory elements have
      been identified functionally by CAT assays. They are located within a 258 base
      points (bp) fragment (pos. 1168 to 1425).

PMID- 9654681
TI  - The gene 4 of rice yellow stunt rhabdovirus encodes the matrix protein.
AB  - The complete nucleotide sequence of the gene 4 of rice yellow stunt rhabdovirus
      (RYSV) was determined from cDNAs corresponding to the viral genomic RNA. Gene 4
      is 913 nucleotides (nt) long, comprising a 17-nt untranslated 5' region, a 786-nt
      open reading frame encoding a polypeptide with a molecular mass of 29,125 Da, and
      a 110-nt untranslated 3' region. Western blot analysis of the RYSV proteins using
      the antiserum raised against the protein expressed from the cloned gene in
      Escherichia coli indicates that gene 4 encodes the M protein of RYSV. Comparisons
      of the deduced amino acid sequence of the M protein of RYSV with those of other
      rhabdoviruses revealed no significant homologies. However, it shared a similar
      basic property and a similar distribution of charges with the other rhabdovirus
      matrix proteins and showed a relatively closer relationship to the sonchus yellow
      net virus (SYNV) M1 protein.

PMID- 9654682
TI  - Biological and genetic differences between lung- and brain-derived isolates of
      maedi-visna virus.
AB  - During the epidemic caused by maedi-visna virus (MVV) of sheep in Iceland, the
      pulmonary affection, maedi, was the predominant clinical manifestation. In some
      flocks, however, a central nervous system (CNS) affection, visna, was the main
      cause of morbidity and mortality. As there is only one breed of sheep in the
      country, host factors did apparently not play an important role in the different
      clinical manifestations. To obtain some information on possible viral genetic
      determinants of neurotropism and neurovirulence we studied both phenotypic and
      genotypic properties of two maedi-visna virus strains; a strain that was
      originally isolated from the brain of sheep with encephalitis (visna), and
      another strain isolated from the lungs of a sheep suffering from pneumonia
      (maedi). The brain isolate was found to grow faster in sheep choroid plexus cells
      than the lung isolate, whereas the growth rate in macrophages was similar for the
      maedi and visna virus strains. Intracerebral inoculation indicated that the visna
      virus isolate induced more severe brain lesions than the maedi isolate. In
      addition, a pathogenic molecular clone derived from a visna strain
      (KV1772kv72/67) was tested for growth in sheep choroid plexus cells and
      macrophages. The molecularly cloned virus retained the fast growth rate in
      choroid plexus cells. The nucleotide sequence of the env gene and the U3 of the
      LTR was determined for the maedi strain and compared to that of the visna
      strains. There was an 11.7% difference in deduced amino acid sequence in the Env
      protein and a 6% difference in the LTR. The molecular clone KV1772kv72/67 will be
      a useful reagent for characterization of viral determinants of cell tropism in
      vitro and possibly neurovirulence in vivo.

PMID- 9654683
TI  - Phylogenetic analysis of triple gene block viruses based on the TGB 1 homolog
      gene indicates a convergent evolution.
AB  - The complete nucleotide sequence of the triple gene block one (TGB 1) of
      cymbidium mosaic potexvirus (CymMV) was compared to those from other potex-,
      carla-, furo- and hordeiviruses. Seven conserved motifs in the TGB 1, including
      the ATP-GTP binding domain (P-Loop) consensus GXXGKTSTS, were found in all four
      virus genera. We propose that all TGBV can be classified into phylogenetic
      clusters based on their TGB 1 homolog genes. These clusters can be further
      delineated to form subgroups. The first cluster comprises the potexviruses which
      are further subdivided into three subgroups; BaMV, FMV, PlaMV and PapMV (subgroup
      Ia); CymMV, PAMV, NMV, SMYEaV and WC1MV (subgroup Ib) and PVX (subgroup Ic). The
      second cluster comprises carlaviruses with a dual subgrouping; CVB, LSV, PVM, PMV
      and ASPV (subgroup IIa) and LVX (subgroup IIb). The third cluster carries the
      most diverse of TGBV comprising furoviruses PCV, PMTV and BSBV (subgroup IIIa)
      and hordeiviruses PSLV, BSMV and LRSV (subgroup IIIb). The phylogenetic
      relationships of triple gene block viruses (TGBV) based on the TGB 1 homolog gene
      indicates a convergent evolution.

PMID- 9654684
TI  - Strawberry vein banding virus--definitive member of the genus Caulimovirus.
AB  - The complete DNA sequence (7876 nucleotides) of strawberry vein banding virus
      (SVBV) has been determined. Seven open reading frames are detected that
      potentially code for proteins of calculated weight 37.8; 18.3; 16.6; 56.0; 81.1;
      59.0 and 12.6 kDa, respectively. Their position on the viral genome is the same
      as that of the corresponding proteins on the cauliflower mosaic virus (CaMV)
      genome. Phylogenetic analysis based on the amino acid sequence of this protein
      shows a closer relationship of SVBV with CaMV, figwort mosaic virus and carnation
      etched ring virus than with other caulimoviruses.

PMID- 9654685
TI  - Molecular characterization of the 3' noncoding region of classical swine fever
      virus vaccine strains.
AB  - The genomes of classical swine fever virus (CSFV) vaccine strains are poorly
      characterized, and the mechanisms for their attenuation remain unknown. The aim
      of the present study was to characterize the 3' noncoding region (3' NCR) of a
      number of attenuated vaccine strains of CSFV in order to examine changes in the
      viral genome after attenuation. The results showed that the 3' NCR:s of Porcivac,
      Rovac, Russian LK and original Chinese vaccine strain contain insertions very
      similar to that present in the published nucleotide sequence of the C-strain.
      Phylogenetic analysis showed that the vaccine strains Porcivac, Rovac and Russian
      LK vaccine were closely related to each other, but that these three strains
      showed a distant relationship with two tested variants of the Chinese vaccine
      strain (C-strain and original Chinese vaccine). The 3' NCR insertion is not
      likely to be a marker for attenuation of the virus, since many CSFV vaccine
      strains do not contain the insertion. The fact that the insertions occur in
      lapinized vaccine strains suggests that these genetic segments were incorporated
      during the adaptation of the virus to the rabbit host system.

PMID- 9654686
TI  - Characterization of bovine adenovirus type 3 early region 2B.
AB  - We have determined the nucleotide sequence of a 6999 base pair region of bovine
      adenovirus-3 covering map units 9.0 to 29.17, which contained the adenovirus
      homologs of IVa2 protein and the DNA replication proteins, precursor of terminal
      protein and DNA polymerase proteins. Analysis of the sequence for cis-acting
      elements suggests that transcripts of DNA polymerase and precursor of terminal
      protein are 3' co-terminal. In addition, this region also contains major late
      promoter sequence. The sequence to the left of IVa2 contains the ORF of pIX with
      a potential TATA box immediately upstream and two polyadenylation consensus
      signals immediately downstream of the ORF.

PMID- 9654687
TI  - Nucleotide sequence of the inter-structural gene region of feline infectious
      peritonitis virus.
AB  - The sequence of the region located between the S and M glycoprotein genes of the
      79-1146 strain of feline infectious peritonitis virus (FIPV) is presented. The
      inter-structural gene region encodes 3 open reading frames (ORFs), termed ORFs
      3a, 3b and 4, with nucleotide sequences conforming to the minimum conserved
      transcription signal upstream of each. An additional ORF, 3x, partially overlaps
      the 3' end of ORF 3a. The FIPV interstructural gene region is identical in length
      when compared to the Insavc-1 strain of canine coronavirus (CCV) but differs from
      various strains of transmissible gastroenteritis virus (TGEV) by the presence of
      deletions and insertions. The sizes of ORF 3a and 4 are conserved in FIPV, TGEV
      and CCV. However, as with CCV, the FIPV ORF 3b is truncated in comparison with
      TGEV.

PMID- 9654688
TI  - [Alcoholism--the accepted addiction].

PMID- 9654689
TI  - The role of (auto-) immunity in atherogenesis.
AB  - Recent data from different laboratories have provided evidence that the first
      stages of atherosclerosis are inflammatory in nature. Research in the last
      decades on this multifactorial disease has primarily focussed on the role of
      lipids, with only a few anecdotal findings suggesting the involvement of the
      immune system in atherogenesis. Within the group of antigens that may be
      responsible for this immunoactivation during atherogenesis, heat shock protein
      (hsp) 65/60 became a serious candidate based on the fact that immunization] of
      normocholesterolemic rabbits with hsp65 leads to the development of
      arteriosclerotic lesions in the aortic intima and these primary inflammatory
      lesions are aggravated by a cholesterol-rich diet, thus completely resembling
      human fatty streaks and atherosclerotic plaques. Furthermore, T cells in
      atherosclerotic lesions of rabbits have been shown to react specially with
      mycobacterial hsp65, suggesting that cell-mediated immune responses to hsp60 are
      also involved in the pathogenesis of this disease In a large epidemiological
      study we demonstrated that serum antibodies to mycobacterial hsp65 were
      significantly increased in clinically healthy subjects with sonographically
      demonstrable carotid atherosclerosis. These antibodies crossreact with human
      hsp60. Thus further elucidation of the role of the role of the immune system in
      atherogenesis could enhance our understanding of the mechanism of this vascular
      disorder, and may lead to new therapeutic strategies for atherosclerosis.

PMID- 9654690
TI  - [Incidence of alcoholism and problem drinking in Austria].
AB  - The prevalence of problem-drinking and alcohol dependence in Austria was assessed
      on the basis of two random samples of the general population drawn in 1995
      (n=216) and in 1996 (n=531). Measurements were performed using the CAGE
      questionnaire (Mayfield et al. 1974). Both cut-off points (> or = 1, > or = 2) of
      the CAGE were used. Both samples showed a very similar prevalence of alcoholism.
      2.2% (95% confidence interval 1.1-3.9%) of the Austrian adult population could be
      regarded as alcohol dependent (four positive CAGE answers). Using a cut-off > or
      = 2, 16-24% of the general population were rated as problem drinkers. The ratio
      of male to female problem drinking was found to be 3:1; this ratio increased to
      4:1 for alcohol dependence. Subjects aged 18 to 59 years were found to be at
      greatest risk for problem drinking. Alcohol dependence showed an equal
      distribution among all age groups with a peak prevalence of 3.7% among 45 to 59
      year-olds. Significant differences in test scores were found for gender in both
      samples, and for age in one sample; marital status had no impact on test scores.
      The findings reported in this study partly confirm the results of Austrian
      alcohol consumption surveys. Although our prevalence estimates rely on self
      report and need to be validated by future epidemiological interview studies, the
      results indicate that alcoholism and problem drinking pose a major public health
      problem.

PMID- 9654691
TI  - [Bone lengthening and soft tissue correction using the Ilizarov technique].
AB  - From March 1989 to September 1995 at the Department of Orthopedic Surgery at the
      Vienna General Hospital 31 limb-lengthenings or corrections of the soft-tissue
      (contractions of joints, clubfeet) using the Ilizarov method were performed. 15
      patients have already finished growth. All complications were analysed according
      to Paley's classification. The tibia-group (n=13) reached an average lengthening
      of 3.5 cm (2-5.7 cm) [16% (6-35%) of the initial length] with a healing index of
      1.7 mo/cm and a complication rate of 42%. In the femur-group (n=8) a mean
      lengthening of 5.4 cm (2.5-9.4 cm) [21% (7-34%) of the initial length] could be
      achieved with a healing rate of 1.3 mo/cm and a complication rate of 40%. The
      ulna-group (n=3) reached an average lengthening of 2.6 cm (2.2-3.4 cm) [21% (17
      24%) or the initial length] with a healing index of 1.4 mo/cm and a complication
      rate of 17%. The knee contracture group (n=2) was free of complications. The
      Ilizarov technique has been performed successfully in a high percentage although
      extensive elongations reported by Ilizarov could not be achieved neither by us
      nor by other authors. The above-mentioned method has been proved to be efficient
      and successful to correct deformities of the soft-tissue.

PMID- 9654692
TI  - [Coping with anger and the premenstrual syndrome].
AB  - OBJECTIVE: Investigations in recent years confirm the importance of "anger coping
      behaviour" for women suffering from different diseases such as migraine, high
      blood pressure and coronary heart disease. The hypothesis for this investigation
      was that "anger-in" coping (anger-suppression) is a possible causal factor in the
      premenstrual syndrome. METHODS: Data analysis was undertaken on 38 patients
      (average age 32 years) fulfilling the inclusion criteria. The Menstrual Distress
      Questionnaire (MDQ) was used for measuring the intensity of premenstrual
      symptoms. As a result of a cluster analysis of MDQ scores, the 38 patients were
      divided into 3 subgroups (group 1: mild symptoms, n = 16; group 2: moderate
      symptoms, n = 10; groups 3: severe symptoms, n = 12). The 3 groups were compared
      by using different questionnaires regarding the variables anger, attitudes to
      menarche and menstrual bleeding, anxiety and depression. Additionally,
      sociodemographic data were obtained and a daily record taken for 2 days
      premenstrually and 5 day postmenstrually of subjective replies to a standardized
      protocol. RESULTS: Contrary to our expectations the results showed no significant
      differences for "anger coping" between the 3 subgroups. Increased daily stress
      (professional and familial double load) statistically significantly influenced
      the intensity of premenstrual symptoms. Additional significant factors were a
      general tendency towards somatization disorder, a negative attitude toward
      menarche and menstrual bleeding, as well as a tendency to depressive mood in
      patients with severe premenstrual symptoms. CONCLUSION: Emotional disorders
      (anger, anxiety) showed less influence on the premenstrual syndrome in the
      investigated women than daily stress and medical anamnesis.

PMID- 9654693
TI  - Adverse events after oral vaccination against cholera with CVD103-HgR.
AB  - The goal of the present study was to evaluate the tolerability and acceptability
      of an oral cholera vaccine (CVD103HgR) in individuals preparing for travel to
      countries endemic for cholera. 2545 Austrian travelers between 6 months and 81.5
      years of age received a single dose of CVD103HgR and were asked to complete a
      questionnaire for documentation of adverse events during a 7 day period post
      immunization. Events were recorded regardless of whether they were caused by
      concomitant vaccinations or other factors and thus, a causative relationship was
      not necessarily present. Despite this drawback and the possibility of
      overreporting this study has proven a low frequency in side effects and the good
      tolerability of CVD103HgR. Occasional gastrointestinal side effects (15%
      diarrhea, 8.1% nausea, 1.1% vomiting) were seen and were of mild character and
      probably a consequence of associated intake of sodium bicarbonate buffer. Other
      events (7% skin eruptions, 2.7% fever) were mild and considered as harmless (or
      not vaccine related). The results show that the oral cholera vaccine CVD103HgR
      was well tolerated and accepted by travelers.

PMID- 9654694
TI  - Aldosterone-producing adenoma associated with foci of myelolipoma.
AB  - The simultaneous occurrence of adrenal myelolipoma and endocrine disorders is
      rare. Myelolipomas have occasionally been found in patients with Cushing's
      syndrome, pheochromocytoma and hyperthyroidism. A recently published study
      described one well-documented case of adrenal adenoma and myelolipoma in a
      patient with Conn's syndrome. In this report the patient had a one-year history
      of treated hyperthyroidism and diagnosed aldosterone-producing adenoma. A
      disseminated adrenal myelolipoma was found within the adrenocortical adenoma. To
      our knowledge this histological finding has not been previously reported in
      association with both Conn's syndrome and hyperthyroidism.

PMID- 9654696
TI  - [New aspects of the pathophysiology of heart failure].
AB  - The progression of heart failure is related to activation of neuroendocrine
      hormone systems. On the level of the myocardium, they contribute to hypertrophy,
      dilation and remodeling of the ventricles. In addition, vascular alterations with
      endothelial dysfunction and alterations of skeletal muscle contribute to clinical
      symptoms of heart failure patients. Changes in ventricular geometry during the
      progression of cardiac diseases are associated with specific subcellular
      alterations on the level of the myocytes. Especially, disturbed intracellular
      Ca2+ handling resulting in altered excitation contraction coupling may lead to
      impaired systolic and diastolic function. Disturbed Ca2+ homeostasis has been
      associated with reduced re-uptake capacity of the sarcoplasmic reticulum for Ca2+
      and an enhanced activity of the sarcolemmal Na+/Ca2+ exchange. In consequence,
      alterations in force-frequency behavior were attributed to a decline in
      intracellular Ca2+ transients at higher stimulation rates. The reduced expression
      of myocardial beta-adrenoceptors and alterations on the level of the G-proteins
      result in a reduced activity of adenylate cyclase and reduction in intracellular
      cAMP content of the myocytes. In consequence, reduced phosphorylation of
      intracellular functional proteins in the failing human heart contributes to
      altered Ca2+ handling. The Frank-Starling-mechanism seems to be unaltered in
      failing isolated human myocardium. Endothelin and angiotensin may contribute to
      the regulation of myocardial contractility in the human heart, but their
      functional relevance in the regulation of myocardial contractility under clinical
      conditions remains to be evaluated.

PMID- 9654697
TI  - [Significance of neuroendocrine parameters in heart failure].
AB  - Heart failure is defined as a malfunction of the cardiac muscle. The ongoing
      interaction between pump failure and the vasculature, however, results in
      symptoms due to malperfusion of the pulmonary and systemic circuit. As a
      consequence, biologic systems of pressure and volume control are activated. In
      the neurohumoral heart failure model the sympathetic nervous system, the renin
      system and endothelin all develop their own pathologic contribution to the
      disease process. Thereby the role of endothelin seems to be special since its
      production is particularly increased in advanced disease. Like angiotensin,
      endothelin has major proliferative properties to promote adverse vascular and
      myocardial growth. The finding of increasing neurohumoral activation as heart
      failure progresses and the role of plasma levels of neurohormones as predictors
      of mortality has rearranged the primary goal of therapy to suppress these
      deleterious neurohumoral systems as completely as possible. Though angiotensin
      converting enzyme inhibitors are currently first line therapy of heart failure,
      uncertainties remain concerning their mechanisms of action and - associated to
      that - optimal dosing.

PMID- 9654698
TI  - [Diagnosis of heart failure].
AB  - Heart failure is a clinical syndrome caused by various etiologic factors. The
      physician should undertake every effort to identify potentially reversible causes
      that lead to heart failure. Therefore one should go through various non-invasive
      as well as invasive diagnostic procedures. The diagnostic tests can be helpful in
      identifying patients with a poor prognosis.

PMID- 9654699
TI  - [Drug therapy of chronic heart failure].
AB  - Prevention of disease leading to cardiac dysfunction, improvement of quality of
      life and reduction of mortality are the primary objectives in the treatment of
      chronic heart failure. The therapeutic possibilities are various, including
      general advices, pharmacological therapy and surgical interventions. Standard
      medical treatment of systolic cardiac dysfunction contains ACE inhibitors,
      diuretics and cardiac glycosides. Beta-blocking agents, oral anticoagulation and
      antiarhythmic drugs can be used in addition. A therapeutic management of chronic
      heart failure tailored to the individual patient has nowadays become available
      due to multiple treatment options.

PMID- 9654700
TI  - [Pacemaker therapy in heart failure].
AB  - Drug therapy is the standard therapy for heart failure. The current state of the
      art does not permit pacemaker therapy as a general recommendation for left
      ventricular failure. Numerous controversial reports have been published on the
      success of pacemaker therapies for congestive heart failure. Iskandrian reported
      on tachycardiac atrial stimulation in 1986. Since 1990 several papers have been
      published on DDD-pacemakers with short AV-time. From the data available to us,
      congestive heart failure is generally not considered a new pacemaker indication.
      In carefully selected patients, however, an improvement in hemodynamics as well
      as in NYHA-classification can be expected, both in acute cases and on a long-term
      basis. In 16 patients Hochleitner demonstrated a significant increase in left
      ventricular ejection fraction, a significant drop in NYHA-classification, heart
      size and an increase in systolic and diastolic blood pressure. Using
      echocardiography Brecker showed a decrease in mitral regurgitation, an increase
      in ventricular filling time and, by means of ergometry, a major increase in
      cardiac output. The hypothesis for the working mechanism is that a shorter AV
      time optimizes the time needed for AV-contraction, thereby reducing mitral
      regurgitation, lengthening ventricular filling time and thus increasing ejection
      fraction. Identification of the patients to whom this hypothesis can be applied
      is difficult but imperative. The optimal AV-time for each patient must be
      established on an individual basis using echocardiography, Doppler sonography and
      ergometry and must be finetuned in follow-up controls. Optimization of AV-time in
      patients with the classic indications for a pacemaker as well as a combination of
      cardioverters and DDD-pacemakers should be aimed for in patients with congestive
      heart failure and high NYHA-classification.

PMID- 9654701
TI  - [Mechanical circulatory support in heart failure].
AB  - Heart transplantation is an established therapy for end-stage cardiac disease.
      The number of organ donors is limited, and the mortality on the waiting list is
      increasing. To give these patients a chance to survive their waiting time,
      chronic mechanical circulatory support, especially left ventricular assist
      devices have been clinically established. The results with this therapy are
      encouraging. Because of these results trials using these devices as an
      alternative for cardiac transplantation are initiated. Due to the further
      development and miniaturization of such devices this indication will become more
      important. The most interesting patients are the one, in which devices could be
      explanted after chronic support, because their myocard has recovered. If we can
      find a way to identify such patients a new form of therapy for end-stage heart
      disease could be established.

PMID- 9654702
TI  - [Guidelines for therapy of chronic pancreatitis. Consensus Conference of the
      German Society of Digestive and Metabolic Diseases. Halle 21-23 November 1996].

PMID- 9654704
TI  - Experiences with novel techniques for reduction of stent flow in transjugular
      intrahepatic portosystemic shunts.
AB  - The transjugular intrahepatic portosystemic shunt (TIPS) may deteriorate liver
      function and can cause encephalopathy in patients with cirrhosis of the liver.
      Then reduction of TIPS flow may be required. We here report several attempts to
      reduce shunt flow in TIPS-induced encephalopathy or liver function impairment
      with novel techniques. Three patients with cirrhosis of the liver were
      investigated: Two with severe recurrent encephalopathy and one with impaired
      liver function following TIPS insertion. Insertion of a reducing stent was
      ineffective to decrease shunt flow velocity in one patient with severe
      coagulopathy. Sufficient reduction of shunt flow was achieved by embolizing the
      space around the hourglass waist of the reducing stent with an occlusion
      emulsion. Insertion of a conventional stent within the preexisting TIPS with or
      without additional embolization reduced TIPS flow in the other patients. After
      reduction of shunt flow encephalopathy improved and liver function returned to
      the level before TIPS, respectively. During follow-up no occlusion of TIPS was
      observed. Thus, reduction of shunt flow velocity can be achieved by insertion of
      an additional stent into a curve-shaped TIPS. Embolization can be helpful to
      decrease TIPS flow, particularly in patients with severe coagulopathy. Reduction
      of TIPS flow can correct TIPS-induced complications.

PMID- 9654703
TI  - [Is chronic laryngitis associated with Helicobacter pylori? Results of a
      prospective study].
AB  - H. pylori is found in the stomach of patients with chronic gastritis. The
      infection is usually transmitted by the gastro-oral route and bacteria could be
      identified in saliva and dental plaque. An essential cause of chronic laryngitis
      is gastroesophageal reflux. The aim of the study was to evaluate if a H.pylori
      associated chronic laryngitis exists. 38 patients with chronic laryngitis
      underwent gastroscopy. Biopsies were taken from the gastric antrum and body,
      lower, middle and upper esophagus. H. pylori was diagnosed by rapid urease test
      and histology. 14 of the patients (36.8%) were H.pylori-positive, but the
      bacteria could not be identified between stomach and larynx. 24 patients were H.
      pylori-negative. Seven patients (18.4%) suffered from esophagitis, six of these
      patients were H. pylori-negative. The H. pylori-infected patients received triple
      therapy for one week, in case of esophogitis Omeprazole 20 mg BID was prescribed.
      Six weeks later a follow-up endoscopy was performed. The eradication rate was
      12/14 (85.7%), in all patients with reflux the esophagitis was cured. The
      laryngitis was clinically and endoscopically unchanged in ten of the twelve
      (83.3%) patients after successful treatment for H. pylori; in the remaining two
      patients as well as in the two H. pylori-positive patients the laryngitis was
      improved. In six out of the seven patients with esophagitis the laryngitis had
      healed completely and was improved in the remaining patient. It may be concluded
      that there is no evidence for the existence of H. pylori-associated laryngitis,
      suggesting that acid reflux is the underlying etiology.

PMID- 9654706
TI  - [Diclofenac-associated acute cholestatis hepatitis].
AB  - Diclofenac is an anti-inflammatory analgesic which is widely used in the therapy
      of inflammatory joint pain. Diclofenac hepatotoxicity ranges from asymptomatic
      elevation of transaminase activity to significant liver disease. 31 cases of
      diclofenac-induced hepatitis with five associated deaths have been already
      reported in the English, French and Spanish literature. We report the case of a
      64-year-old patient who was admitted to the hospital with an icteric hepatitis of
      sudden onset. The only drug that was taken before admission was diclofenac in a
      daily dose of 150-200 mg because of a spondylodiscitis. Work-up of the patient
      included ERCP, laparoscopy and liver biopsy and excluded other reasons of a
      cholestatic hepatitis. Discontinuation of diclofenac resulted in normalization of
      transaminase activity and bilirubin concentration within four months. The
      frequent use of diclofenac and the possibility of fatal liver damage highlights
      the need that diclofenac-toxicity should be considered in the differential
      diagnosis of acute cholestatic hepatitis.

PMID- 9654705
TI  - [Follow-up of benign recurrent intrahepatic cholestasis (Summerskill-Walshe
      Tygstrup syndrome) over 46 years].
AB  - Benign recurrent intrahepatic cholestasis (BRIC or Summerskill-Walshe-Tygstrup
      syndrome) is a rare autosomal recessive form of liver disease, which usually
      becomes manifest in childhood. Characteristic are recurrent episodes of jaundice
      and itching of different duration. Number and duration of episodic attack and
      asymptomatic period develop individually. For diagnosis of BRIC following
      criteria are proposed: At least three episodes of severe jaundice and pruritus
      with biochemical evidence of cholestasis, normal intra-and extrahepatic bile
      ducts on cholangiography, absence of a factor known to produce intrahepatic
      cholestasis and symptom-free intervals of several months or years. Often the
      diagnosis of BRIC is made very late and patients have to suffer invasive
      investigations (explorative laparotomy). Because of the unknown
      pathophysiological mechanism there is no specific treatment. We report on a 53
      year-old patient with jaundice, severe pruritus, vomiting, loss of hair and
      weight, extreme sleeplessness and intractable cough. At the onset of the attack
      an increase of serum bilirubin concentration and serum alkaline phosphatase was
      observed, whereas aspartate and alanine aminotransferase and gamma
      glutamyltransferase were normal. Histological findings of liver biopsy revealed
      accumulation of bile plugs in bile canaliculi. The long-term follow-up of our
      patient confirms that the prognosis is good.

PMID- 9654707
TI  - [Cryoglobulinemia and chronic liver diseases].
AB  - Cryoglobulinemia can be associated with several infections, immunoproliferative
      tumors, chronic liver, renal and systemic autoimmune diseases. In the first part
      of the publication the authors give a review of the main clinical and laboratory
      properties of cryoglobulins. In essential mixed cryoglobulinemia syndrome
      (purpura, arthralgia, weakness) clinical and laboratory signs of damaged liver
      function can often be seen. However, there are mixed cryoglobulins in chronic
      liver disease of different etiologies as well. In 30-94% of patients with
      hepatitis C virus infection and hepatitis C virus-induced chronic liver diseases
      laboratory signs (occasionally clinical symptoms as well) or mixed
      cryoglobulinemia can be diagnosed. Serological markers of hepatitis C virus
      infection have been found in the cryoprecipitates of patients with mixed
      cryoglobulinemia. A high prevalence of mixed cryoglobulins in serum of patients
      with chronic hepatitis C virus infection and hepatitis C virus-induced chronic
      liver disease suggests that this virus has a significant role in the pathogenesis
      of mixed cryoglobulins. Also, an impaired clearance function of the liver in the
      uptake of cryo(immuno)complexes may be an important causative factor in the
      production of cryoglobulins in chronic liver diseases of different etiologies.

PMID- 9654708
TI  - [Prevention and early detection of colorectal carcinoma by endoscopic
      examinations].
AB  - People at average risk for colorectal cancer (asymptomatic, age > or = 45 years,
      no risk factors) are offered fecal occult blood testing each year and
      sigmoidoscopy every five years. In case of a positive fecal occult blood test,
      examination of the whole colon by colonoscopy should be performed. Colorectal
      cancer risk is significantly lowered by endoscopic polypectomy in patients with
      adenomas. After complete removal of adenomatous polyps a control colonoscopy is
      advised three years after the initial examination. People with a positive family
      history of colorectal cancer or adenomatous polyps, of inherited polyposis
      syndromes, of a hereditary non-polyposis colorectal cancer, after polypectomy,
      after resection of colorectal cancer and with inflammatory bowel disease possess
      an increased risk for the development of colorectal cancer. Surveillance
      recommendations in these cases are detailed. In order to increase the cost
      benefit ratio in surveillance after curative resection of colorectal cancer the
      frequency of the surveillance procedures can be reduced. In patients with total
      or extensive ulcerative colitis colonoscopy with multiple biopsies should be
      performed after a disease duration of eight to ten years, further recommendations
      depend on the histopathologic results.

PMID- 9654709
TI  - [Laparoscopic resection in comparison with open resection of adenocarcinoma of
      the colon].

PMID- 9654710
TI  - [Ethical guidelines for performing percutaneous endoscopic gastrostomy (PEG
      catheter)].

PMID- 9654711
TI  - [Prognostic value of immunohistochemically identifiable tumor cells in lymph
      nodes of patients with RO-resected esophageal carcinoma].

PMID- 9654712
TI  - [Fetal pulse oximetry].

PMID- 9654713
TI  - [Placentation in the human: a transplantation or tumor model?].
AB  - In human placentation, anchoring villi develop to attach the placenta to the wall
      of the uterus. This attachment is brought about by extensive infiltration of the
      maternal tissue by cytotrophoblast cells of fetal origin. As trophoblast cells do
      not express classical histocompatibility antigens (HLA antigens), increasing
      doubt has been cast upon the "transplantation" model of pregnancy. However, more
      recently discovered, previously unknown HLA antigens on the invasive
      cytotrophoblast cells could lead to maternal immune responses similar to those
      observed following organ transplantation. Nevertheless, the biological behaviour
      of the invasive cytotrophoblast cells suggests more parallels with the processes
      of invasion and metastasis seen in malignant tumours, although there is
      regulation of the timing and extent of cytotrophoblast invasion of the uterus in
      normal pregnancy. In this survey, findings relating to the control of
      infiltration by the cytotrophoblast are reviewed, with particular reference to
      immunology and tumour biology. Possible effects on pregnancy and parturition due
      to failure of the regulatory processes involved in placentation are discussed.

PMID- 9654714
TI  - [Single intrauterine fetal death in twin pregnancy].
AB  - During a 11 year period (1984-1994) we identified and analysed at the Department
      of Obstetrics, University Hospital of Zurich, among 541 twin pregnancies 19 with
      single intrauterine death (SIUD) in the second and third trimester. The preterm
      delivery rate was 68% and much higher compared to singleton pregnancies at the
      same institution (17%). The caesarean section rate was 47% and also higher
      compared to singleton pregnancies (21%) but lower than in a normal twin
      collective (61%). Two of the surviving twins showed malformations. One of them
      has in addition of porencephaly, probably due to disruption syndrome. In 12 out
      of 19 case a monochorionic placenta was found including 5 with twin-twin
      transfusion syndrome. Surprisingly 8 out of 19 dead fetuses had a velamentous
      insertion of the umbilical cord. This might suggest a causal relationship to
      SIUD. 95% showed the same sex. Maternal blood coagulation disorders are rare.
      From our results we conclude that SIUD is associated with an increased preterm
      delivery and caesarean section rate. Monochorionic twins and twins with
      concordant sex demonstrate the highest risk for SIUD. The twin-twin transfusion
      syndrome is the main single cause for SIUD. The pathophysiologic role of
      velamentous insertion remains unclear.

PMID- 9654715
TI  - [Erythropoietin and obstetric factors--evaluation with special reference to sex
      differences].
AB  - OBJECTIVE: We evaluated fetal Erythropoietin (EPO) in a clinical obstetrical
      environment, aiming to collect more information upon its role in diagnosis of
      fetal stress. As it is known that EPO cannot pass the placental barrier, we
      restricted to measure the concentration in the umbilical artery (UA) immediately
      after delivery. PATIENTS AND METHODS: EPO was correlated to relevant obstetrical
      parameters. We looked for each parameter that was tested for differences in fetal
      sex. For this purpose, the statistics were performed by means of the Behrens
      Fisher-Test (meaning a special application of the Student-T-Test). This device is
      an algorithm developed to compare regressions. For significance, a confidence
      level of less 5% was accepted. For the rest, we only used descriptive devices.
      RESULTS: We found weak but positive correlation to gestational age for both
      sexes. No correlation was calculated for the duration of parturition or the birth
      weight. Highly significant differences were found for respiratory values of blood
      gases, taken from the UA when differentiated for fetal sex: males showed a strong
      and negative correlation for pO2 (r(m)= -0.45); the female EPO-level was not
      influenced by decreasing O2-level (r(w)= +0.06, p > 0.01). Similar results could
      be found for pCO2. (r(m)= +0.36; r(w)= -0.07; p < 0.01. Not significant, but
      comparable differences for the EPO-level in fetal blood were found for pH and
      base deficit. CONCLUSIONS: If we accept that the EPO-level in fetal blood rises
      with relevant oxygen deficiency, then females seems to be better protected
      against damage from distress. This observation is congruent with the clinical
      experience from the authors who have the subjective impression that female sex is
      advantageous in harmful deliveries.

PMID- 9654716
TI  - [Kinetocardiotocography--KCTG--during pregnancy in an ambulatory care patient
      sample and in hospitalized patients with special reference to tocolysis].
AB  - With kinetocardiotocography (KCTG), fetal movements can be registered parallel to
      the fetal heart rate. Hewlett Packard equipment of the series 1350 A allows the
      movements to be registered an quantified on the CTG paper. In this study,
      hospitalized pregnant women > 26 gestational weeks (GW) on i.v. tocolysis, and
      out-patients > 34 GW at the out patient department were examined with KCTG and
      the results compared. A wide distribution of fetal activity was seen in both
      groups. With advancing pregnancy, the number of fetal movements as well as the
      duration of activity per time unit decreased, whereas the length of time of
      individual movements slightly increased, in both groups. No statistically
      significant difference was seen between different gestational ages nor between
      the two groups. KCTG is being increasingly used to monitor the fetal condition,
      especially for risk pregnancies. It can provide additional information in the
      form of a biophysical variable.

PMID- 9654717
TI  - [Monstrous fetal lymphangioma of the thoracic wall bilaterally. Case report and
      discussion of diagnosis and perinatal management].
AB  - Prenatal diagnosis, perinatal management, and surgical treatment of children with
      lymphangioma can cause considerable difficulties. This paper presents a case of a
      thoracic wall lymphangioma diagnosed in the seventeenth week of pregnancy, with
      quickly developed monstrous dimensions. The postnatal phase was complicated by
      preterm delivery in the 32nd week or pregnancy, bleeding in the tumor and
      mechanical compression of the thorax by the huge masses. Pediatric intensive care
      and surgical treatment save the child. Cosmetic result is convenient. By example
      of the presented case the literature, problems of diagnosis, perinatal management
      and nomenclature of lymphangioma are discussed.

PMID- 9654718
TI  - [Wilson disease and pregnancy. Review of the literature and case report].
AB  - Wilson's disease is an autosomal recessive disorder of copper metabolism. Since
      the introduction of penicillamine treatment successful pregnancies have been
      reported. However little is known about the risks of breast feeding in patients
      on this medication. We describe the case of a patient suffering from Wilson's
      disease, who had two uncomplicated pregnancies and breast fed both children for a
      period of three months each. In the 22 year old gravida I para I the diagnosis of
      Wilson's disease had been previously made by liver biopsy and penicillamine
      therapy had been begun. At the time of her first presentation at our department
      she was 8 week pregnant. Her renal and liver function were normal. Neurologic or
      psychiatric symptoms were not observed. At 18 weeks the dosage of penicillamine
      was reduced from 900 mg/d to 750 mg/d. The course of the pregnancy remained
      uneventful. At 38 + 1 weeks a healthy boy of 3100 gm was delivered. 19 months
      later the patient presented again in the 16th week of her second pregnancy.
      Concerning Wilson's disease no major changes were observed, especially liver and
      renal function were not impaired. The dosage of penicillamin was reduced from 900
      mg/d to 750 mg/d during the 21st week. The pregnancy again was uncomplicated and
      at 38 + 2 weeks resulted in the spontaneous deliver of a healthy boy, weighting
      3940 gm. Both children were breast fed over a period of three months and with the
      exception of an icterus prolongatus no adverse effects were noted.

PMID- 9654719
TI  - [Monozygotic multiple pregnancies with acardiac anomalies].
AB  - The acardiac fetus is a rare anomaly of about 1 percent of monozygotic
      pregnancies, occurring in approximately 1 in 35,000 pregnancies. The special
      hemodynamic circumstances of the normal heart having to pump an excessive amount
      of blood for a long period of time will influence the chance of survival of this
      fetus. In two case-report with many figures pathologic-anatomical problems and
      prospective management to improve the outcome of monozygotic multiple pregnancies
      complicated by acardiac malformation were presented. The pathogenesis of
      metabolic dysbalance in these pregnancies was discussed.

PMID- 9654720
TI  - [An unusual course of fetal gastroschisis].
AB  - We report on prenatal diagnosis of gastroschisis at 20th gestational week. In
      addition to gastroschisis intraabdominal intestinal stenosis was detected. As a
      consequence cesarean section was planned close to term. Control examinations in
      the last trimester didn't confirm initial diagnosis so that the recommended mode
      of delivery was changed. However postpartum diagnosis again confirmed the early
      diagnosis of gastroschisis including spontaneous necrosis of dislocated
      intraamniotic intestinal parts. The course demonstrates that even at unambiguous
      prenatal diagnosis control examinations are recommended as dynamic changes may
      occur in the second and third trimester. Thus mode of delivery may have to be
      adapted close to term to reduce maternal risk.

PMID- 9654721
TI  - [Don't wait until the press discovers you].

PMID- 9654722
TI  - [Myopia or retinal detachment in the obstetric clinic].

PMID- 9654723
TI  - [Obstetrical management in enucleated myoma].

PMID- 9654724
TI  - [30 years specialist for pediatric and adolescent psychiatry and psychotherapy].

PMID- 9654725
TI  - [Incidence of psychiatric symptoms and somatic complaints in 4- to 10-year-old
      children in Germany as judged by parents--a comparison of norm-oriented and
      criteria-oriented models].
AB  - OBJECTIVES: To analyze the frequency of behavioral/emotional problems and somatic
      complaints of children aged four to ten as rated by their parents. METHOD: The
      analysis is based on the PAK-KID study on behavioural and emotional problems and
      psychosocial competencies of children and adolescents in Germany. In a nationally
      representative sample of N = 1030 children aged four to ten years the parents
      rated their child using the Child Behavior Checklist. RESULTS: The prevalence
      rates of the symptoms are presented. Additionally global prevalence rates based
      on three different models were calculated and compared. They range from 13.1% to
      28.3%. The issues of defining cutoffs necessary for the calculation of prevalence
      rates are discussed.

PMID- 9654726
TI  - [Variability of inpatient child and adolescent psychiatry--results of a
      multicenter documentation].
AB  - OBJECTIVE: For the first time in the German-speaking countries a complete
      evaluation of all 1236 inpatient treatment episodes within one year of
      investigation was carried out. METHOD: Case-related patient documentation at all
      of the 13 clinics for child and adolescent psychiatry in Lower Saxony and Bremen
      were evaluated. RESULTS: Data from all clinics agreed widely on the following: 1.
      the divergent family structures of the young patients compared to those of the
      general public, 2. a high degree of individual psychotherapy, and 3. the
      inclusion of the patient's social circumstances in the individual psychotherapy.
      Nonetheless, results for most of the variables assessed differed strongly.
      Inpatient child and adolescent psychiatric care thus seems to vary highly among
      clinics within the same epidemiological area. CONCLUSIONS: Hence, even when the
      reported number of episodes is high, no general conclusions on inpatient child
      and juvenile psychiatric treatment can be drawn on the basis of admissions data
      for individual clinics. Interinstitutional comparisons must be made on the
      assumption that there is no prototype clinic for child and adolescent psychiatry.
      Additional general conclusions include the lack of a disorder-specific approach
      to treatment. The entry of a large number of patients into foster or state homes
      following inpatient treatment reflects the impact upon them of abnormal
      psychosocial circumstances, as well as their decreased psychosocial adaption.

PMID- 9654727
TI  - [Comparison of 2 clinics with reference to axis 5 of the MAS: different patient
      populations or regional characteristics?].
AB  - OBJECTIVE: The university departments of child psychiatry in Cologne and Berlin
      were compared to assess whether quantitative differences in reported abnormal
      psychosocial situations (Axis 5 MAS of ICD-10) are due to a difference in patient
      population or coding practices or to particular regional conditions. METHOD: Data
      were analyzed for 593 patients seen in Cologne in 1992/93 and for 685 patients
      seen in Berlin in the same period. The broader social situation was described by
      sociodemographic data from the respective city. RESULTS: Berlin showed about
      twice as many psychosocial stressors per patient as Cologne. Consistent
      relationships between axis 5 stress ratings and other parameters indicated the
      validity of the data. Only a few points of inconsistency in the data were found.
      The sociodemographic data for both cities revealed a greater number of single
      parents as well a a higher rate of suicide in Berlin. CONCLUSIONS: Indicators for
      the validity of the clinical data analyzed were found. Some special internal
      clinical and regional conditions were identified as contributing to the
      quantitative differences between the two university departments.

PMID- 9654728
TI  - [Effects and significance of specific spelling problems in young adults-
      empirical studies in an epidemiologic patient sample].
AB  - OBJECTIVE: 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 spelling problems is investigated. METHOD: Using the same set of
      data, the effect of alternative definitions and methodological procedures on the
      prevalence of specific spelling retardation is shown. The virtual consequences of
      various norm-orientated definitions of cases is discussed with reference to
      external empirical criteria. RESULTS: Particularly, obsolete norms lead to a
      large overestimation of cases. In the present study case definitions of specific
      spelling retardation based on substantial criteria result in prevalence rates
      between 6 and 9 percent. Academic achievement is considerably affected by
      persisting specific spelling problems and the attendance of secondary schools is
      rare, in spite of sufficient nonverbal intelligence. CONCLUSIONS: Because of the
      high impact of spelling ability for educational success, dyslexic children need
      help by early intervention. Furthermore scholastic promotion is necessary to
      enable a school carer appropriate to the intellectual possibilities of the child.

PMID- 9654729
TI  - [Differences in the spontaneous organization of auditory verbal learning in brain
      damaged adolescents].
AB  - OBJECTIVE: Subjective organization (SO) of verbal memory and learning was
      investigated for 44 adolescent patients. METHOD: The patients were subdivided
      into four clinical groups according to localization of lesion: right hemisphere
      (RH), left hemisphere (LH), frontal (FL), and brain stem (SL). RESULTS: As
      expected RH patients performed best on this verbal learning task, whereas FL and
      SL patients demonstrated very poor SO, indicating their failure in categorize
      memory input. LH patients increased SO, following successive trials, which
      suggests an active learning strategy. CONCLUSIONS: It is argued that the use SO
      analysis in neuropsychology will stimulate the course of further research towards
      attaining a better understanding of memory and learning impairments and their
      remission in brain-damaged patient.

PMID- 9654730
TI  - Renal impairment in hepatic cryotherapy.
AB  - Cryoshock is a syndrome of coagulopathy, renal, and pulmonary injury following
      cryotherapy, and its etiology is unknown. The aim of this study was to assess the
      impact of hepatic cryotherapy on renal function, and whether this effect is
      related to volume of cryotherapy, and to identify any predictors of renal
      impairment in patients who undergo cryotherapy. A retrospective analysis of all
      patients with primary or secondary hepatic malignancy treated with cryotherapy
      from April 1990 to October 1996 was conducted. Ten of 204 patients with renal
      impairment (elevation in creatinine of greater than 0.02 mmol/L for more than 2
      days postprocedure) were identified. One patient has postoperative pancreatitis
      with late renal impairment (20 days) and was excluded. The severity of renal
      impairment was usually modest (mean rise in creatinine of 0.31 mmol/L; SD, 0.19).
      Two patients required temporary hemodialysis. Only one patient, who had
      significant cardiac disease, had associated pulmonary injury and shock.
      Demographic data in both groups were comparable, except for a trend toward more
      noncolorectal cancer patients in the renal impairment group (4/9 vs 33/194).
      Patients in the renal impairment group had a greater number of lesions than those
      of the nonrenal impairment group (3.4 vs 2.1, p < 0.01), as well as larger lesion
      diameter (2.9 vs 1.9, p < 0.01), increased freezing time (74.7 vs 44.3, p <
      0.01), and a higher aspartate transaminase (AST) (2254 vs 1157, p < 0.01). This
      study suggests that renal impairment is more likely to be seen in patients
      undergoing more extensive cryotherapy. The number and diameter of lesions
      together with AST data link renal injury with magnitude of liver injury--all
      renal impairment patients had an AST > 1000, compared with only 28% of patients
      who did not.

PMID- 9654731
TI  - Cytosolic pH variations in perfused rat liver at 4 degrees C: role of
      intracellular buffering power.
AB  - The effect of low temperature on cytosolic pH regulation and buffering capacity
      was evaluated in the isolated rat liver. The pH changes were followed by
      phosphorus-31 nuclear magnetic resonance. Cooling from 37 to 4 degrees C, with
      Krebs-Heinseleit perfusion at an external pH of 7.35, induced an alkaline shift
      in cytosolic pH (pHcyt) of 0.13 or 0.75 pH units in the presence of bicarbonate,
      respectively (dpH cys/dT values were 0.004 and 0.022 unit/degrees C. With 4
      degrees C perfusion, in the presence or absence of bicarbonate, acute changes of
      external pH (from 7.40 to 5.90) did not affect pHcyt. In contrast, intracellular
      loading with isobutyric acid or NH4Cl induced rapid pHcyt variations. The
      intrinsic buffering power value (10 to 50 slykes) measured in the absence of
      bicarbonate depended on pHcyt. The larger value was observed for pHcyt 7.30, a
      value near the pK value of the imidazole group of intracellular proteins at 4
      degrees C. The presence of bicarbonate modified the amplitude of the pHcyt change
      by increasing the total buffering power. It was demonstrated that during
      hypothermia, ionic carriers are inactivated and the charged forms of molecules
      are unable to cross the cell membrane; thus, the pHcyt homeostasis depends
      essentially on intracellular buffering power.

PMID- 9654733
TI  - Membrane permeability characteristics of metaphase II mouse oocytes at various
      temperatures in the presence of Me2SO.
AB  - In this study, the hydraulic conductivity (Lp), Me2SO permeability (PMe2SO), and
      the reflection coefficients (sigma) and their activation energies were determined
      for Metaphase II (MII) mouse oocytes by exposing them to 1.5 M Me2SO at
      temperatures of 30, 20, 10, 3, 0, and -3 degrees C. These data were then used to
      calculate the intracellular concentration of Me2SO at given temperatures.
      Individual oocytes were immobilized using a holding pipette in 5 microliters of
      an isosmotic PBS solution and perfused with precooled or prewarmed 1.5 M Me2SO
      solutions. Oocyte images were video recorded. The cell volume changes were
      calculated from the measurement of the diameter of the oocytes, assuming a
      spherical shape. The initial volume of the oocytes in the isoosmotic solution was
      considered 100%, and relative changes in the volume of the oocytes after exposure
      to the Me2SO were plotted against time. Mean (means +/- SEM) Lp values in the
      presence of Me2SO were (LpMe2SO) at 30, 20, 10, 3, 0 and -3 degrees C were
      determined to be 1.07 +/- 0.03, 0.40 +/- 0.02, 0.18 +/- 0.01, 7.60 x 10(-2) +/-
      0.60 x 10(-2), 5.29 x 10(-2) +/- 0.40 x 10(-2), and 3.69 x 10(-2) +/- 0.30 x 10(
      2) microns/min/atm, respectively. The PMe2SO values were 3.69 x 10(-3) +/- 0.3 x
      10(-3), 1.07 x 10(-3) +/- 0.1 x 10(-3), 2.75 x 10(-4), +/- 0.15 x 10(-4), 7.83 x
      10(-5) +/- 0.50 x 10(-5), 5.24 x 10(-5) +/- 0.50 x 10(-5), and 3.69 x 10(-5) +/-
      0.40 x 10(-5) cm/min, respectively. The sigma values were 0.70 +/- 0.03, 0.77 +/-
      0.04, 0.81 +/- 0.06, 0.91 +/- 0.05, 0.97 +/- 0.03, and 1 +/- 0.04, respectively.
      The estimated activation energies (Ea) for LpMe2SO, and PMe2SO, and sigma were
      16.39, 23.24, and -1.75 Kcal/mol, respectively. These data may provide the
      fundamental basis for the development of more optimal cryopreservation protocols
      for MII mouse oocytes.

PMID- 9654735
TI  - Temperature threshold and preservation of signaling for mitochondrial membrane
      proteins during ischemia in rabbit heart.
AB  - Temperature modulates both myocardial energy requirements and production. We have
      previously demonstrated that myocardial protection induced by hypothermic
      adaptation preserves expression of genes regulating heat shock protein and the
      nuclear-encoded mitochondrial proteins, the adenine nucleotide translocator
      isoform 1 (ANT1), and the beta subunit of F1-ATPase (beta F1-ATPase). This
      preservation is associated with a reduction in ATP depletion similar to that
      noted in cardioplegic arrested hearts preserved at a critical temperature (30
      degrees C) or below. We tested the hypothesis that expression of these genes may
      also be subject to this temperature threshold phenomenon. Isolated perfused
      rabbit hearts were subjected to ischemic cardioplegic arrest at 4, 30, or 34
      degrees C for 120 min. Cardiac function indices and steady-state mRNA levels for
      ANT1, beta F1-ATPase, and HSP70-1 were measured prior to ischemia (B) and after
      45 min of reperfusion. Cardiac function was significantly depressed in the 34
      degrees C group. Ischemia at 34 degrees C reduced steady-state mRNA levels for
      ANT1 and beta F1-ATPase from B, but these levels were similarly preserved at 4
      and 30 degrees C. HSP70-1 levels were mildly elevated (fourfold) above B to
      similar levels at all three temperatures. These results indicate that mRNA
      expression for ANT1 and beta F1-ATPase is specifically preserved in a pattern
      consistent with the temperature threshold phenomenon. HSP70-1 expression is not
      influenced by ischemic temperature. Preservation of gene expression for these
      mitochondrial proteins implies that signaling for mitochondrial biogenesis or
      resynthesis is maintained after ischemic insult.

PMID- 9654736
TI  - Evolution of repetitive proteins: spider silks from Nephila clavipes
      (Tetragnathidae) and Araneus bicentenarius (Araneidae).
AB  - Spider silks are highly repetitive proteins, characterized by regions of
      polyalanine and glycine-rich repeating units. We have obtained two variants of
      the Spidroin 1 (NCF-1) silk gene sequence from Nephila clavipes. One sequence
      (1726 bp) was from a cloned cDNA, and the other (1951 bp) was from PCR of genomic
      DNA. When these sequences are compared with each other and the previously
      published Spidroin 1 sequence, there are differences due to sequence
      rearrangements, as well as single base substitutions. These variations are
      similar to those that have been reported from other highly repetitive genes, and
      probably represent the results of unequal cross-overs. We have also obtained 708
      bp of sequence from pCR of genomic DNA from Araneus biocentenarius. This sequence
      shows considerable similarity to a dragline sequence (ADF-3) from A. diadematus,
      as well as Spidroin 2 (NCF-2) from N. clavipes. Minor but consistent differences
      in the repeating unit sequence between A. bicentenarius and A. diadematus suggest
      that concerted evolution or gene conversion processes are acting to maintain
      similarity among repeat units within a single gene.

PMID- 9654737
TI  - Identification of proteins and developmental expression of RNAs encoded by the
      65A cuticle protein gene cluster in Drosophila melanogaster.
AB  - Proteins of the third instar larval cuticle of Drosophila melanogaster, LCP5
      LCP9, were purified and their N-terminal sequences determined. Three of these
      proteins (LCP5, 6, and 8) were found to be encoded by two multicopy genes
      previously mapped to the gene cluster at 65A 5-6 on the left arm of the third
      chromosome. The analysis of the patterns of developmental expression of the 8
      distinct genes at this site showed that all but two were expressed during larval
      life. The patterns fell into three groups: one where expression was all through
      larval life, one where expression was primarily in the third instar, and one only
      during the production of the adult cuticle. One duplicated gene was not expressed
      in the Canton S strain at any time from the embryo to adult ecdysis. These
      findings indicate that there is not a unique set of cuticle proteins in the third
      versus the first and second instar larval cuticles and indicates that overlapping
      gene sets in several different gene clusters encode the proteins of the cuticle
      of different developmental stages.

PMID- 9654738
TI  - alpha-Crystallin protein cognates in eggs of the moth, Plodia interpunctella:
      possible chaperones for the follicular epithelium yolk protein.
AB  - alpha-Crystallin protein cognates were found in germ cells of the Indianmeal
      moth, Plodia interpunctella (Shirk and Zimowska, 1997). A cDNA clone of 674 bp
      with a single open reading frame was isolated for a 25,000 molecular weight
      polypeptide member of this family, alpha CP25, and a single transcript of
      approximately 700 bp was found in the ovary of vitellogenic females. Both the DNA
      sequence and predicted amino acid sequence showed considerable homology with the
      embryonic lethal gene, l(2)efl, in Drosophila melanogaster. In addition to the
      sequence for l(2)efl, the predicted amino acid sequence for acp25 also showed
      significant sequence similarly with the alpha-crystallin A chain polypeptides
      from the lenses of vertebrae eyes. An N-terminal hydrophobic aggregation site and
      a C-terminal protective binding site common to alpha-crystallin proteins were
      present in the predicted acp25 and l(2)efl amino acid sequences, while only the C
      terminal protective binding site was present in the small heat shock protein
      sequences from D. melanogaster. This evidence suggests that although the alpha
      crystallin protein cognates in P. interpunctella evolved from a gene common with
      small heat shock protein genes, the amino acid sequence has converged on a
      structure similar to that of alpha-crystallin proteins. Native immunoblot
      analysis showed that the alpha-crystallin proteins formed high molecular weight
      complexes with the follicular epithelium yolk protein (FEYP) but not vitellin in
      yolk. An electroblot binding assay was used to show that the germ-cell alpha
      crystallins of P. interpunctella bind specifically with the FEYP and that the
      binding was reversible in the presence of ATP or low pH. This evidence in
      conjunction with the evidence that the alpha-crystallins and FEYP form a stable
      complex that co-purifies from native egg proteins suggests that the alpha
      cystallin cognates function as chaperones for the follicular epithelium yolk
      proteins in the embryos of P. interpunctella.

PMID- 9654739
TI  - Molecular cloning of chitinase cDNAs from the silkworm, Bombyx mori and the fall
      webworm, Hyphantria cunea.
AB  - cDNAs encoding chitinases were cloned and characterized from Bombyx mori and
      Hyphantria cunea, and their gene expression during the metamorphosis was also
      studied. The chitinase cDNA from B. mori encodes a protein of 565 amino acids
      with a calculated molecular mass of 63.4 kDa and the H. cunea chitinase cDNA
      encodes a protein of 553 amino acids with a calculated molecular mass of 62.0
      kDa. Amino acid alignment of the two chitinases revealed 75% homology and 77-80%
      with M. sexta chitinase. The putative cleavage site of the signal peptide was
      between amino acid residues 20 and 21 for both chitinases. There were three
      potential N-glycosylation sites in the chitinase of B. mori at the amino acid
      residues 86-89, NFTS 304-307, NATG, 398-401, NYTV, whereas two potential N
      glycosylation sites were present at the amino acid residues 86-89, NFTA and 304
      307, NATG, in that of H. cunea. Southern blot analysis of total genomic DNA
      suggested that the B. mori genome has only one chitinase gene detectable by the
      cDNA probe and the H. cunea genome has one or two chitinase gene copies. Northern
      analysis indicated that gene expression was up-regulated during the molting
      process, larval-pupal transformation and pupal-adult transformation, when
      enzymatic degradation of cuticle was occurring.

PMID- 9654740
TI  - Identification and cDNA cloning of novel juvenile hormone responsive genes from
      fat body of the bean bug, Riptortus clavatus by mRNA differential display.
AB  - Juvenile hormone (JH) induces termination of diapause and initiation of
      reproductive maturation in the adult female bean bug, Riportus clavatus. Applying
      PCR-based differential display, we have identified four novel JH-responsive
      cDNAS, that is, three repressible (JR-1, 2 and 3) and one inducible (JI-1). These
      DNA fragments were partially sequenced and compared with sequences in the data
      base. JR-3 was shown to have similarity to the transferrins of other insects,
      which have been reported as JH-suppressed genes. JI-1 has similarity to
      vitellogenin of Aedes aegypti. On the other hand, JR-1-1 and 2 have no
      significant similarity to other known sequences. For JR-1, the full cDNA sequence
      was determined: it contained 913 bp, encoding 194 amino acid residues with a
      calculated M.W. of 21,531 Da in the mature protein. A total of six JH-responsive
      genes or cDNAs (four suppressible and two inducible or stimulated), including the
      already isolated JH-responsive cyanoprotein genes (CP-alpha and beta), have been
      isolated and are available for further comparative analysis of gene structure and
      regulatory mechanisms in the same tissue under the same hormonal conditions.

PMID- 9654741
TI  - Characterization and cDNA cloning of a hemoprotein in the salivary glands of the
      blood-sucking insect, Rhodnius prolixus.
AB  - Three major red hemoproteins, named RpSG I, II (identical with prolixin-S) and
      III, in the salivary glands of the blood-sucking insect, Rhonius prolixus, show
      homology in N-terminal amino acid (AA) sequences, and are immunologically
      related. We focussed on one of these proteins, RpSG-I, in this paper. RpSG-I in
      fresh salivary gland extract was separated into two components (Ia and Ib) by
      isoelectric focussing gel electrophoresis. Absorption spectra of RpSG-Ia and Ib
      showed Soret peaks at 400 nm and 420 nm, respectively, suggesting that they are
      nitric oxide (NO)-unbound and -bound hemoproteins and function as NO-carriers.
      RpSG-I is stage-specific in appearance, being absent in 3rd and 4th instar
      nymphs, appearing and increasing gradually in 5th (last) instar nymphs after
      engorgement, and present in the adult stage. We purified RpSG-I from salivary
      gland extract by size exclusion and ion exchange HPLCs. It is a single
      electrophoretic band with an absorption peak at 400 nm, representing the NO
      unbound molecule. Full-size cDNA of RpSG-I was cloned by screening with a
      specific polyclonal antibody from a salivary gland cDNA library. Sequence
      analysis of RpSG-I cDNA showed an open reading frame encoding a signal peptide
      (23 AA) and mature protein (179 AA) of 19,778 daltons. The deduced N-terminal AA
      sequence of the RpSG-I was identical with that of the hemoprotein reported as
      nitrophorin-3 (Champagne et al., 1995).

PMID- 9654742
TI  - Irreversible high pressure inactivation of beta-galactosidase from Kluyveromyces
      lactis: comparison with thermal inactivation.
AB  - High hydrostatic pressure and high temperature are both shown to induce
      inactivation of Kluyveromyces lactis beta-galactosidase in deionised water and
      their respective effects are compared. These two physical parameters lead to
      similar inactivation kinetics which can be suitably represented by series-type
      models. The plot of half-lives as a function of pressure is close to the same
      plot towards temperature. Thus, the same inactivation rate constant can be
      obtained in two different ways: an increase in pressure at room temperature or an
      increase in temperature at atmospheric pressure (e.g. 125 MPa at 25 degrees C or
      45 degrees C at 0.1 MPa for a kappa 1 value about 28 x 10(-2) min -1). When beta
      galactosidase was prepared in 0.1 M potassium phosphate buffer pH 7.3, its
      stability in extreme conditions of pressure as at high temperature was strongly
      enhanced. This stabilizing effect of the buffer was essentially attributed to a
      pH-effect by comparison with the behaviour of the enzyme in a similar buffer but
      with a 10-fold lower ionic strength.

PMID- 9654743
TI  - Secretion in Escherichia coli and phage-display of recombinant insulin-like
      growth factor binding protein-2.
AB  - Insulin-like growth factors (IGFs) promote cell growth and differentiation. Their
      actions are regulated by six different, but related, binding proteins (IGFBPs).
      To investigate the molecular interactions between IGFs and IGFBPs, an Escherichia
      coli based production method and a phage display system has been developed. The
      cDNA for bovine IGFBP-2 was inserted between regions coding for the pelB signal
      sequence and geneIII product, g3p, of bacteriophage fd in a phagemid vector to
      generate pGF14. The coding sequences of IGFBP-2 and g3p were separated by an
      amber stop codon and a flexible linker containing the cleavage recognition site
      for H64A subtilisin. Using this system in BL21, a non-supE strain lacking ompT,
      most product, approximately 4 mg 1(-1) of IGFBP-2, was obtained in the growth
      medium. The bacterially derived IGFBP-2 had a correct N-terminal sequence,
      molecular mass on SDS-PAGE and the same affinity for IGF-1 and IGF-II as IGFBP-2
      from mammalian cells. In a supE strain of E. coli, IGFBP-2 was produced as an IGF
      binding fusion to g3p. Procedures for display and approximately 10000 fold
      enrichment of IGFBP-2 bearing phage using adsorption to IGF-II coated microtitre
      plates were developed. Thus IGFBP-2 can be secreted in E. coli and displayed on
      filamentous phage. These can be selectively enriched by binding to immobilised
      IGF-II.

PMID- 9654744
TI  - Production and characterization of monoclonal anti-idiotypic antibody exhibiting
      a catalytic activity similar to carboxypeptidase A.
AB  - A new approach for producing catalytic anti-idiotypic antibody was developed. A
      monoclonal anti-idiotypic antibody which was induced against carboxypeptidase A
      (CPA) showed the catalytic activity similar to the original antigen. The activity
      of the catalytic antibody was investigated. Rabbits were immunized by bovine
      pancreas carboxypeptidase A. The antiserum was purified and used as antigen to
      immunize BALB/c mice to induce monoclonal anti-idiotypic antibodies. Screened for
      enzymatic activities, the monoclonal antibody 32C3 showed esterase activity. The
      hydrolysis of hippuryl-DL-phenyllactic acid by McAb 32C3 followed the enzymatic
      kinetics. In our experimental system, Kcat value was 0.0123 min-1 and Km was
      0.04M. The acceleration rate was 1750 times compared to the rate of self
      hydrolysis of the substrate. This hydrolysis reaction can be competitively
      inhibited by hydrocinnamic acid. This method could be effective to obtain
      catalytic antibodies with the characters close to natural enzymes.

PMID- 9654745
TI  - In vitro selection of HIV-1 TAR variants by the Tat protein.
AB  - Starting from a pool of 10(13) RNA sequences, we isolated a number of TAR RNA
      variants after nine rounds of selection by binding to recombinant Tat in vitro
      (SELEX procedure). Sequence analysis of part of the selected molecular species
      indicated that two TAR variants (clones A and B) were, respectively, represented
      five and four times. These two groups of sequences constituted approximately 25%
      of the total number of analyzed clones (9/34). As far as the primary and
      presumptive secondary structures of the wild-type TAR are concerned, the selected
      A and B variants showed an almost complete sequence conservation of the Tat
      binding domain, but the configuration of this nucleotide region differed within
      the secondary structure. Despite this difference, as verified by gel retardation
      and filter binding assays, both the A and B variants bound Tat in vitro with an
      affinity that was very close to that of the wild-type TAR. Conversely, neither
      variant sustained Tat-mediated trans-activation in vivo when they replaced the
      wild-type TAR inside the long terminal repeat of HIV_1. Taken together, our
      results suggest that these TAR variants have lost the ability to bind cell
      factor(s) in vivo and may therefore represent useful decoys for the inhibition of
      HIV-1 replication.

PMID- 9654746
TI  - A bienzyme electrode for L-malate based on a novel and general design.
AB  - The coimmobilization of a NAD(P) + -dependent dehydrogenase with salicylate
      hydroxylase (SHL, EC 1.14.13.1) in front of a Clark-electrode yields a flexible
      new design for dehydrogenase based biosensors. The feasibility of the approach
      has been tested with malic enzyme (MDH, EC 1.1.1.40) as the dehydrogenase,
      resulting in a novel L-malate sensor. It had substantial advantages over the
      biosensor approaches reported earlier: effective re-oxidation of NADPH by SHL
      yielded an extended linear range from 0.01 to 1.2 mmol 1(-1) L-malate and
      strongly reduced NADP+ -requirement (<0.025 mmol 1(-1)), while the working
      stability was increased to more than 30 days. The results obtained from six real
      samples showed a close correlation with the standard enzymatic method. The
      presented scheme with SHL and the Clark-electrode can be employed together with
      any NAD(P)+ -dependent dehydrogenase.

PMID- 9654747
TI  - Purification and characterization of a highly selective epoxide hydrolase from
      Nocardia sp. EH1.
AB  - A highly enantioselective, soluble epoxide from Nocardia sp. EH1 was purified to
      homogeneity via a four-step procedure: (i) hydrophobic interaction chromatography
      on Phenyl Sepharose CL-4B, (ii) anion exchange chromatography on SOURCE 30Q,
      followed by (iii) a second hydrophobic interaction chromatography on Phenyl
      Sepharose HP, and finally (iv) gel-filtration on Superdex 75 HR 10/30. The pure
      protein was shown to be a monomer of integral of 34 kDa possessing an optimum pH
      of 8-9. Neither UV-absorbing cofactors nor metal ions were required for activity.
      In contrast to whole-cell activity, the partially purified enzyme proved to be
      considerably less stable. Stabilization was achieved by addition of non-ionic
      detergents such as Tween 80 or Triton X-100, causing a shift of the temperature
      optimum from 35 to 40 degrees C. Both effects combined led to an enhancement of
      the relative activity of up to approximately 150% of that of the native enzyme.

PMID- 9654748
TI  - Recombinant tissue plasminogen activator (rt-PA) in fibrinolytic therapy.

PMID- 9654749
TI  - Cinoxacin complexes with divalent metal ions. Spectroscopic characterization.
      Crystal structure of a new dinuclear Cd(II) complex having two chelate-bridging
      carboxylate groups. Antibacterial studies.
AB  - Several cinoxacin (HCx) complexes with divalent metal ions have been prepared and
      characterized by spectroscopic techniques. The crystal structure of
      [Cd2(Cx)4(H2O)2].10H2O has been determined by X-ray diffraction. The complex is
      triclinic, space group P1 with unit-cell dimensions: a = 10.412(2), b =
      11.119(2), c = 13.143(6)A, chi== 76.78(4) degrees, beta = 74.59(3) degrees, gamma
      = 77.12(3) degrees, V = 1406.0(8) A3. In this complex each cadmium atom is
      heptacoordinated: the metal environment is formed by two Oketo and two Ocarbox
      atoms from two different cinoxacinate monoanions, two carboxylate oxygen atoms
      from a third cinoxacinate ligand and by one water oxygen atom on the seventh
      position. Two of the cinoxacinate ions act as tridentate chelate and bridging
      ligands and the other one as a bidentate chelate ligand. In the bridging
      monoanions the carboxylate group is behaving as a chelate ligand. All the
      complexes were screened for their activity against several bacteria, showing
      activity similar to that of cinoxacin. Additionally, the number of bacteria
      killed after 3 h of incubation with cinoxacin, [Cu(Cx)2].2H2O and
      [Co(Cx)3]Na.10H2O complexes was determined against E. coli ATCC 25922; the copper
      compound presents paradoxical effect which has been described and related to the
      mechanism of action of quinolones.

PMID- 9654750
TI  - Interactions of trialkyllead compounds with rat liver mitochondria.
AB  - The interactions of two trialkyllead (TAL) compounds, (trimethyl)Pb-Cl and
      (tributyl)Pb-Cl, with mitochodria from rat liver have been studied. A stimulation
      of the respiratory rate induced by the trialkyllead compounds added at low doses
      was observed which was not dependent on the presence of chloride in the medium.
      In contrast with the major current view, we propose that trialkyllead compounds
      behave as uncouplers of the oxidative phosphorylation and not (or not only) as Cl
      /OH- exchangers. In fact the present results suggest that the TAL compounds enter
      the mitochondria as (alkyl)3Pb+ cations and are extruded as electroneutral
      (alkyl)3 Pb-OH compounds, the overall result being the transport of a proton
      through the membrane as in the case of classical uncouplers. The uncoupling
      effect could explain the toxicity of the compounds as a result of the decrease in
      the energy level of the cell. Furthermore, such a mechanism, in which the uptake
      of TAL compounds is supposed to be driven by a negative potential, could explain
      their preferential toxicity for neuronal cells, which maintain a higher negative
      inside potential than most other cell types.

PMID- 9654751
TI  - Binuclear chloro-bridged palladated and platinated complexes derived from p
      isopropylbenzaldehyde thiosemicarbazone with cytotoxicity against cisplatin
      resistant tumor cell lines.
AB  - Two novel dimeric chloro-bridged complexes [Pd (p-is. TSCN) (mu-Cl)]2, 2, and [Pt
      (p-is. TSCN)(mu-Cl)]2, 3, where p-is. TSCN = p-isopropylbenzaldehyde
      thiosemicarbazone, 1, have been synthesized and characterized by IR and NMR
      spectroscopy. The in vitro antitumor activity shown by both compounds against
      several human and murine cell lines sensitive and resistant to the clinically
      used drug cisplatin (cis-DDP) suggests that compounds 2 and 3 may be endowed with
      important anticancer properties. Thus, compounds 2 and 3 not only show IC50
      values in the microM range as cis-DDP but also display cytotoxic activity in
      tumor cell lines resistant to this drug. The analysis of the interaction of these
      binuclear p-is. TSCN compounds with DNA secondary and tertiary structures
      indicate that they form DNA interhelical cross-links, a biochemical property that
      may be involved in their mechanism of action.

PMID- 9654752
TI  - Diorganotin(IV) complexes of pyridoxal thiosemicarbazone: synthesis,
      spectroscopic properties and biological activity.
AB  - The complexes [SnR2(L)] (R = Me, Et, Bu, Ph; H2L = pyridoxal thiosemicarbazone)
      have been prepared and characterized. In the light of the spectral properties of
      the complexes in the solid state (IR, mass, Mossbauer) the bideprotonated
      thiosemicarbazonato anion is O(phenolic)-, N(3)-, S-bonded to the tin atom which
      probably has trigonal bipyramidal coordination with N(3) atom and R groups
      occupying equatorial positions. NMR ( 1H, 13C and 119Sn) data in CDCl3 or DMSO-d6
      suggest that this coordinative picture remains in these solutions. The ethyl,
      butyl and phenyl derivatives suppress proliferation of Friend erithroleukaemia
      cells (FLC). Of the pyridoxal thiosemicarbazone complexes so far evaluated.
      [SnBu2(L)] and [SnPh2(L)] showed the lowest thresholds for inhibition of FLC
      proliferation. The effects of these compounds on DMSO-induced differentiation of
      FLC, DNA synthesis and reverse transcriptase were also assayed.

PMID- 9654753
TI  - A role for HEM2 in cadmium tolerance.
AB  - A Candida glabrata cadmium-sensitive mutant partially defective in glutathione
      production and exhibiting a complete absence of phytochelatins was used to clone
      a gene required for Cd tolerance. Transformation of the Cd-sensitive mutant with
      a genomic library from the wild-type C. glabrata led to the cloning of a gene
      that restored Cd tolerance and formation of Cd-glutathione and Cd-phytochelatin
      complexes. The cloned gene showed high levels of nucleic acid and protein
      sequence homology to the HEM2 genes, encoding porphobilinogen synthases, from
      several sources. It was shown that the C, glabrata Cd-sensitive mutant indeed
      exhibited a significant reduction in porphobilinogen synthase levels. The cloned
      C. glabrata gene complemented a hem2 mutant of Saccharomyces cerevisiae and
      restored porphobilinogen synthase activity in the mutant. The Cd sensitive mutant
      predictably showed decreased levels of sulfite reductase that requires siroheme,
      a metabolite produced in the heme biosynthetic pathway. The addition of cysteine,
      but not methionine, increased glutathione levels and Cd tolerance of both the
      wild-type and the mutant strain. However, addition of hemin chloride and
      methionine together restored Cd tolerance indicating that heme was required for
      transsulfuration of homocysteine to cysteine.

PMID- 9654754
TI  - The potential of matrix-assisted laser desorption/ionization mass spectrometry in
      the quality control of water buffalo mozzarella cheese.
AB  - Adulteration by addition of bovine milk to water buffalo milk employed for
      mozzarella cheese production is often observed. Water buffalo milk and mozzarella
      cheese were analysed by matrix-assisted laser desorption/ionization mass
      spectrometry in order to achieve their rapid and accurate characterization and to
      evaluate possible fraudulence in mozzarella cheese production.

PMID- 9654755
TI  - Hb Sagami [beta 139(H17)Asn-->Thr]: a new hemoglobin variant not detected by
      isoelectrofocusing and propan-2-ol test, was detected by electrospray ionization
      mass spectrometry.

PMID- 9654756
TI  - Measuring individual differences in implicit cognition: the implicit association
      test.
AB  - An implicit association test (IAT) measures differential association of 2 target
      concepts with an attribute. The 2 concepts appear in a 2-choice task (2-choice
      task (e.g., flower vs. insect names), and the attribute in a 2nd task (e.g.,
      pleasant vs. unpleasant words for an evaluation attribute). When instructions
      oblige highly associated categories (e.g., flower + pleasant) to share a response
      key, performance is faster than when less associated categories (e.g., insect &
      pleasant) share a key. This performance difference implicitly measures
      differential association of the 2 concepts with the attribute. In 3 experiments,
      the IAT was sensitive to (a) near-universal evaluative differences (e.g., flower
      vs. insect), (b) expected individual differences in evaluative associations
      (Japanese + pleasant vs. Korean + pleasant for Japanese vs. Korean subjects), and
      (c) consciously disavowed evaluative differences (Black + pleasant vs. White +
      pleasant for self-described unprejudiced White subjects).

PMID- 9654757
TI  - Understanding and assessing the motivations of volunteers: a functional approach.
AB  - The authors applied functionalist theory to the question of the motivations
      underlying volunteerism, hypothesized 6 functions potentially served by
      volunteerism, and designed an instrument to assess these functions (Volunteer
      Functions Inventory; VFI). Exploratory and confirmatory factor analyses on
      diverse samples yielded factor solutions consistent with functionalist
      theorizing; each VFI motivation, loaded on a single factor, possessed substantial
      internal consistency and temporal stability and correlated only modestly with
      other VFI motivations (Studies 1, 2, and 3). Evidence for predictive validity is
      provided by a laboratory study in which VFI motivations predicted the persuasive
      appeal of messages better when message and motivation were matched than
      mismatched (Study 4), and by field studies in which the extent to which
      volunteers' experiences matched their motivations predicted satisfaction (Study
      5) and future intentions (Study 6). Theoretical and practical implications are
      discussed.

PMID- 9654758
TI  - Personality and social change: individual differences, life path, and importance
      attributed to the women's movement.
AB  - This article identifies antecedent characteristics of individuals who found the
      women's movement important and then shows how finding it important was associated
      with personality change. Eighty-six women provided personality and life data as
      college seniors in 1958 or 1960, prior to the onset of the women's movement, and
      in 1981, after the movement gained momentum. A combination of openness, ambition,
      and dissatisfaction, as assessed by California Psychological Inventory (CPI; H.
      Gough, 1957/1966) in college, and subsequent life path from ages 28 to 43
      significantly predicted importance attributed to the women's movement (IWM). On
      CPI scales, IWM was associated with significant increases on scales including
      Dominance, Self-Acceptance, Empathy, Psychological Mindedness, and Achievement
      via Independence. Correlates of IWM with self-reported feelings at ages 33 and 43
      and observer-based personality ratings at age 43 supplemented analyses of
      personality change. Findings support the utility of examining the impact of
      social change on personality.

PMID- 9654759
TI  - Heritability of facet-level traits in a cross-cultural twin sample: support for a
      hierarchical model of personality.
AB  - The common variance among personality traits can be summarized in the factors of
      the five-factor model, which are known to be heritable. This study examined
      heritability of the residual specific variance in facet-level traits from the
      Revised NEO Personality Inventory. Analyses of raw and residual facet scales
      across Canadian (183 monozygotic [MZ] and 175 dizogotic [DZ] pairs) and German
      (435 MZ and 205 DZ pairs) twin samples showed genetic and environmental
      influences of the same type and magnitude across the 2 samples for most facets.
      Additive genetic effects accounted for 25% to 65% of the reliable specific
      variance. Results provide strong support for hierarchical models of personality
      that posit a large number of narrow traits in addition to a few broader trait
      factors or domains. Facet-level traits are not simply exemplars of the broad
      factors they define; they are discrete constructs with their own heritable and
      thus biological basis.

PMID- 9654760
TI  - Dysphoria and social interaction: an integration of behavorial confirmation and
      interpersonal perspectives.
AB  - To investigate the process by which dysphoric persons are rejected by others,
      authors integrated behavioral confirmation and interpersonal theories of
      depression. The expectations of nondysphoric perceiver participants (college
      students) were manipulated, such that half expected to interact with a same-sex
      dysphoric target and half expected to interact with a same-sex nondysphoric
      target. The targets' actual mood status was consistent or inconsistent with these
      expectations. Pre- and postinteraction impressions, as well as postinteraction
      acceptance of partners, were solicited from perceivers and targets (N = 240).
      Audiotaped verbal behaviors were coded during the 1st and last 3 min of the
      interactions. Acceptance of targets and verbal behaviors were an interactive
      function of perceivers' expectancies and targets' mood status, such that
      dysphoric targets who were expected to be nondysphoric were the least accepted
      group and had the most dysfunctional interactions.

PMID- 9654761
TI  - A multimodal analysis of personal negativity.
AB  - This study examined how unhappiness and self-dissatisfaction are related to
      behavior, self-perception, social reputation, and the way one is treated by
      others. Varying in personal negativity (PN)--a composite of unhappiness,
      dissatisfaction with life, low self-esteem, and nonclinical depression--146
      undergraduates (82 women and 64 men) engaged in 3 interactions. Participants'
      behavior and the behavior of their interaction partners was coded from
      videotapes. Personality ratings were obtained from participants and from 2 close
      acquaintances. PN was closely associated with maladaptive social interactions,
      negative behavioral responses by others, and a negative social reputation and
      self-image. Although women more clearly expressed PN behaviorally, men and women
      showed generally similar patterns of correlates. These results suggest that even
      subclinical levels of unhappiness and self-dissatisfaction may have important
      consequences.

PMID- 9654762
TI  - Consequences of self-handicapping: effects on coping, academic performance, and
      adjustment.
AB  - Self-handicappers erect impediments to performance to protect their self-esteem.
      The impediments may interfere with the ability to do well and, as such, may
      result in poor adjustment. Using a longitudinal design, the present studies
      examined prospective effects of self-handicapping on coping, academic
      performance, and several adjustment-related variables (e.g., self-esteem). It was
      found that, compared to low self-handicappers, high self-handicappers reported
      higher usage of coping strategies implying withdrawal and negative focus. High
      self-handicappers performed less well academically, an effect that was mediated
      in part by poor study habits. Finally, high self-handicapping resulted in poorer
      adjustment over time, and poorer adjustment resulted in higher self-handicapping
      over time. These relations are consistent with the idea of a vicious cycle in
      which self-handicapping and poor adjustment reinforce one another.

PMID- 9654763
TI  - Optimism is associated with mood, coping, and immune change in response to
      stress.
AB  - This study explored prospectively the effects of dispositional and situational
      optimism on mood (N = 90) and immune changes (N = 50) among law students in their
      first semester of study. Optimism was associated with better mood, higher numbers
      of helper T cells, and higher natural killer cell cytotoxicity. Avoidance coping
      partially accounted for the relationship between optimism and mood. Among the
      immune parameters, mood partially accounted for the optimism-helper T cell
      relationship, and perceived stress partially accounted for the optimism
      cytotoxicity relationship. Individual differences in expectancies, appraisal, and
      mood may be important in understanding psychological and immune responses to
      stress.

PMID- 9654764
TI  - Adult attachment styles: their relations to family context and personality.
AB  - This study used a sample of 304 adults to examine mean differences in family
      climate and personality variables on the basis of individuals' attachment styles.
      Also examined was whether mean differences varied by age group. Findings showed
      significant main effects of attachment style, but no Attachment Style x Age Group
      interactions. Compared with adults with an insecure attachment style, persons
      with a secure attachment style described their family of origin and their current
      family more positively and scored higher on personality variables indicative of
      self-confidence, psychological well-being, and functioning in the social world.
      When the family climate and personality variables were included in a discriminant
      function analysis, 2 significant functions were obtained. The 1st function
      discriminated adults with a positive self-model from those with a negative self
      model. The 2nd function contrasted participants with a positive other-model from
      those with a negative other-model. Thus, this study provided evidence in support
      of the self- and other-models as the fundamental dimensions of adults' attachment
      system.

PMID- 9654765
TI  - A comparison of coping assessed by ecological momentary assessment and
      retrospective recall.
AB  - Recent research suggests that retrospective coping assessments may not correspond
      well with day-to-day reports. The authors extended this work by examining the
      correspondence between short-term (within 48 hr) retrospective coping reports and
      momentary reports recorded via a palm-top computer close in time to when the
      stressor occurred. There was relatively poor correspondence between the 2
      assessments. Some reports of momentary coping were not reported retrospectively,
      and some coping reported retrospectively was not reported at the time the
      stressor occurred. Cognitive coping was more likely to be underreported
      retrospectively; behavior coping was overreported. Participants were consistent
      in their discrepancies, but there was no correspondence between discrepancy rates
      and demographic or personality variables.

PMID- 9654766
TI  - Maladaptive achievement patterns: a test of a diathesis-stress analysis of
      helplessness.
AB  - The present study tested the assumptions, derived from a diathesis-stress model,
      that students' perceptions of autonomy-support in their classroom produce a
      relatively intrinsic as opposed to extrinsic motivational approach to academic
      tasks and that this approach, in turn, predicts qualitatively different responses
      to uncontrollable events. It was further assumed that students' motivational
      orientation would be more reliable than attributional style or perceptions of
      competence in predicting achievement patterns, including performance level after
      failure, use of adaptive attributions, and overall achievement scores. Results
      supported these predictions and further demonstrated, in longitudinal analyses,
      that motivational orientation may contribute to the formation of perceptions of
      competence and attributional style in students.

PMID- 9654767
TI  - Dynamics of membrane excitability determine interspike interval variability: a
      link between spike generation mechanisms and cortical spike train statistics.
AB  - We propose a biophysical mechanism for the high interspike interval variability
      observed in cortical spike trains. The key lies in the nonlinear dynamics of
      cortical spike generation, which are consistent with type I membranes where
      saddle-node dynamics underlie excitability (Rinzel & Ermentrout, 1989). We
      present a canonical model for type I membranes, the theta-neuron. The theta
      neuron is a phase model whose dynamics reflect salient features of type I
      membranes. This model generates spike trains with coefficient of variation (CV)
      above 0.6 when brought to firing by noisy inputs. This happens because the timing
      of spikes for a type I excitable cell is exquisitely sensitive to the amplitude
      of the suprathreshold stimulus pulses. A noisy input current, giving random
      amplitude "kicks" to the cell, evokes highly irregular firing across a wide range
      of firing rates; an intrinsically oscillating cell gives regular spike trains. We
      corroborate the results with simulations of the Morris-Lecar (M-L) neural model
      with random synaptic inputs: type I M-L yields high CVs. When this model is
      modified to have type II dynamics (periodicity arises via a Hopf bifurcation),
      however, it gives regular spike trains (CV below 0.3). Our results suggest that
      the high CV values such as those observed in cortical spike trains are an
      intrinsic characteristic of type I membranes driven to firing by "random" inputs.
      In contrast, neural oscillators or neurons exhibiting type II excitability should
      produce regular spike trains.

PMID- 9654768
TI  - Category learning through multimodality sensing.
AB  - Humans and other animals learn to form complex categories without receiving a
      target output, or teaching signal, with each input pattern. In contrast, most
      computer algorithms that emulate such performance assume the brain is provided
      with the correct output at the neuronal level or require grossly unphysiological
      methods of information propagation. Natural environments do not contain explicit
      labeling signals, but they do contain important information in the form of
      temporal correlations between sensations to different sensory modalities, and
      humans are affected by this correlational structure (Howells, 1944; McGurk &
      MacDonald, 1976; MacDonald & McGurk, 1978; Zellner & Kautz, 1990; Durgin &
      Proffitt, 1996). In this article we describe a simple, unsupervised neural
      network algorithm that also uses this natural structure. Using only the co
      occurring patterns of lip motion and sound signals from a human speaker, the
      network learns separate visual and auditory speech classifiers that perform
      comparably to supervised networks.

PMID- 9654769
TI  - A hierarchical model of binocular rivalry.
AB  - Binocular rivalry is the alternating percept that can result when the two eyes
      see different scenes. Recent psychophysical evidence supports the notion that
      some aspects of binocular rivalry bear functional similarities to other bistable
      percepts. We build a model based on the hypothesis (Logothetis & Schall, 1989;
      Leopold & Logothetis, 1996; Logothetis, Leopold & Sheinberg, 1996) that
      alternation can be generated by competition between top-down cortical
      explanations for the inputs, rather than by direct competition between the
      inputs. Recent neurophysiological evidence shows that some binocular neurons are
      modulated with the changing percept; others are not, even if they are selective
      between the stimuli presented to the eyes. We extend our model to a hierarchy to
      address these effects.

PMID- 9654770
TI  - Pattern generation by two coupled time-discrete neural networks with synaptic
      depression.
AB  - Numerous animal behaviors, such as locomotion in vertebrates, are produced by
      rhythmic contractions that alternate between two muscle groups. The neuronal
      networks generating such alternate rhythmic activity are generally thought to
      rely on pacemaker cells or well-designed circuits consisting of inhibitory and
      excitatory neurons. However, experiments in organotypic cultures of embryonic rat
      spinal cord have shown that neuronal networks with purely excitatory and random
      connections may oscillate due to their synaptic depression, even without
      pacemaker cells. In this theoretical study, we investigate what happens if two
      such networks are symmetrically coupled by a small number of excitatory
      connections. We discuss a time-discrete mean-field model describing the average
      activity and the average synaptic depression of the two networks. Depending on
      the parameter values of the depression, the oscillations will be in phase,
      antiphase, quasiperiodic, or phase trapped. We put forward the hypothesis that
      pattern generators may rely on activity-dependent tuning of synaptic depression.

PMID- 9654771
TI  - Computational studies of lateralization of phoneme sequence generation.
AB  - The mechanisms underlying cerebral lateralization of language are poorly
      understood. Asymmetries in the size of hemispheric regions and other factors have
      been suggested as possible underlying causal factors, and the corpus callosum
      (interhemispheric connections) has also been postulated to play a role. To
      examine these issues, we created a neural model consisting of paired cerebral
      hemispheric regions interacting via the corpus callosum. The model was trained to
      generate the correct sequence of phonemes for 50 monosyllabic words (simulated
      reading aloud) under a variety of assumptions about hemispheric asymmetries and
      callosal effects. After training, the ability of the full model and each
      hemisphere acting alone to perform this task was measured. Lateralization
      occurred readily toward the side having larger size, higher excitability, or
      higher-learning-rate parameter. Lateralization appeared most readily and
      intensely with strongly inhibitory callosal connections, supporting past
      arguments that the effective functionality of the corpus callosum is inhibitory.
      Many of the results are interpretable as the outcome of a "race to learn" between
      the model's two hemispheric regions, leading to the concept that asymmetric
      hemispheric plasticity is a critical common causative factor in lateralization.
      To our knowledge, this is the first computational model to demonstrate
      spontaneous lateralization of function, and it suggests that such models can be
      useful for understanding the mechanisms of cerebral lateralization.

PMID- 9654772
TI  - Debunking the alleged resurrection of the sodium pump hypothesis.

PMID- 9654773
TI  - Lanthionine ketimine and S-(2-aminoethyl)-L-cysteine ketimine induce the tyrosyl
      phosphorylation of 45 kDa protein in parallel with its stimulation of superoxide
      generation in human neutrophils.
AB  - Human peripheral blood polymorphonuclear leukocytes were preincubated with
      lanthionine, S-(2-aminoethyl)-L-cysteine, and some of their derivatives found in
      normal human urine and bovine brain. Among these compounds, lanthionine ketimine
      and to a lesser extent S-(2-aminoethyl)- L-cysteine ketimine enhanced the N
      formyl-methionyl-leucyl-phenylalanine-induced superoxide generation. These
      ketimines induced tyrosyl phosphorylation of 45 kDa protein of cells. The tyrosyl
      phosphorylation was markedly increased with time, and the phosphorylation process
      was dependent on the concentration of both ketimines. However, lanthionine, 1,4
      thiomorpholine-3,5-dicarboxylic acid, S-(2-aminoethyl)-L-cysteine and 1,4
      thiomorpholine-3-carboxylic acid were without effect both on superoxide
      generation and on tyrosyl phosphorylation of 45 kDa protein. Lanthionine ketimine
      and S-(2-aminoethyl)-L-cysteine ketimine also enhanced superoxide generation
      induced by opsonized zymosan but not the one induced by arachidonic acid and
      phorbol 12-myristate 13-acetate. Ketimine-primed superoxide generation and
      tyrosyl phoshorylation of 45 kDa protein were inhibited by genistein, an
      inhibitor of protein tyrosine kinase, but not by 1-(5-isoquinoline sulfonyl)-2-
      methylpiperazine, an inhibitor of protein kinase C.

PMID- 9654774
TI  - Electrolyte concentration in skeletal muscles and plasma of rats during and after
      exposure to hypokinesia and hyperhydration.
AB  - The objective of this investigation was to determine electrolyte concentration in
      skeletal muscles and plasma of rats during 90 days of hypokinesia (decreased
      motor activity) and 15 days of posthypokinesia. The animals were divided into
      three groups: 1) supplemented hypokinetic rats (SHR), i.e., rats subjected to
      hypokinesia and taking daily an additional 9 ml water per 100 g body weight plus
      6 ml isotonic sodium chloride per 100 g body weight; 2) unsupplemented
      hypokinetic rats (UHR), i.e., rats subjected to hypokinesia; 3) vivarium control
      rats (VCR), i.e., rats placed under ordinary vivarium conditions. Hypokinesia was
      effected by keeping SHR and UHR animals in small individual cages that restricted
      their movements in all directions without hindering food and water intake.
      Determinations were made of water and electrolyte (sodium potassium, calcium,
      magnesium) concentrations in muscle tissue; concentration of electrolytes
      (sodium, potassium, calcium, magnesium, phosphorus, chloride) in plasma; body
      weight; fluid consumed and eliminated in urine; whole blood, red blood cell and
      plasma volumes; hematocrit content and plasma protein concentration. During the
      hypokinetic period, electrolytes and water concentration in muscle tissue and
      plasma electrolyte concentration changes significantly in the UHR when compared
      with SHR and VCR while in comparing the SHR with the VCR these same variables had
      no significant changes. Body weight, water balance, volume of blood, red blood
      cell and plasma, hematocrit and plasma protein concentration in the UHR were also
      significantly different when compared with the VCR. No significant difference was
      seen in these parameters when the SHR and VCR were compared. During the initial
      seven days of the posthypokinetic period the changes in these same parameters
      remained significantly different in the UHR when compared with the SHR and VCR
      while changes were insignificant when the SHR and the VCR were compared. It was
      concluded that daily hyperhydration may be used to attenuate or normalize water
      and electrolyte concentrations in muscles and plasma of rats subjected to
      prolonged restriction of motor activity.

PMID- 9654775
TI  - Biotransformation of shiromodiol diacetate, myli-4(15)-en-9-one and myliol by
      Aspergillus niger.
AB  - Microbiol biotransformation of shiromodiol diacetate from Neolitsea serisea
      koids, and of myli-4(15)-en-9-one and myliol from the liverwort Mylia taylorii,
      were carried out with Aspergillus niger IFO 4407. A. niger hydroxylated the allyl
      position (C-2) of shiromodiol diacetate, and one of the geminal dimethyl groups
      of myli-4(15)-en-9-one and myliol regioselectively. The structures of these
      transformants were elucidated by spectral analysis and confirmed by X-ray
      analysis.

PMID- 9654776
TI  - Steroidal saponins from the underground parts of Ruscus aculeatus and their
      cytostatic activity on HL-60 cells.
AB  - Phytochemical examination of the underground parts of Ruscus aculeatus has been
      undertaken as part of systematic study of plants of the Liliaceae. Six new
      spirostanol saponins and five new furostanol saponins were isolated, and their
      structures were assigned on the basis of spectroscopic analysis, including two
      dimensional NMR techniques, and hydrolysis. Ruscogenin diglycoside with three
      acetyl groups attached to the inner galactosyl moiety and its corresponding 26
      glucosyloxyfurostanol saponin showed cytostatic activity on leukemia HL-60 cells.

PMID- 9654777
TI  - Alphitol, a phenolic substance from Alphitonia zizyphoides which inhibits
      prostaglandin biosynthesis in vitro.
AB  - The new phenolic compound, 3,5-dihydroxy-4-methoxy phenethyl alcohol, named
      alphitol, and betulinic acid were from the bark of Alphitonia zizyphoides. The
      chemical structure of alphitol was determined by mass spectrometry in combination
      with one and two dimensional NMR, including HMBC. Both compounds inhibited
      prostaglandin biosynthesis in vitro, alphitol with an IC50 value of 0.66mM, which
      is of the same magnitude as acetyl salicylic acid.

PMID- 9654778
TI  - A hydroxytetradecatrienoic acid from Mycosphaerella rubella.
AB  - Investigations on the acidic fractions from extracts of a culture of
      Mycosphaerella rubella led to the isolation of a new unsaturated dihydroxy acid,
      6,13-dihydroxytetradeca-2,4,8 trienoic acid, and two of its derivatives, which
      are probably artifacts. Their structures were determined on the basis of H and C
      NMR evidence. The absolute configuration of the chiral centres of the new acid
      was elucidated using the modified Mosher's method.

PMID- 9654779
TI  - Triterpenoid saponins and sapogenins from Vaccaria segetalis.
AB  - Four new triterpenoid saponins, vaccarosides E, F, G and H were isolated from the
      seeds of Vaccaria segatalis and were respectively defined to be 3-O-beta-D
      galactopyranosyl(1-->2)-beta-D-glucuronopyranosyl] quillaic acid 28-O-beta-D
      xylopyranosyl-(1-->4)-chi-L-rhamnopyranosyl-(1-->2)- [chi-L-arabinofuranosyl-(1-
      >3)]-beta-D-4-O-acetylfucopyranoside; 3-O-[beta-D-galactopyranosyl-(1-->2)-beta-D
      glucuronopyranosyl] 3beta,4chi,16chi-trihydroxy-23-norolean-12-en-28-oic acid 28
      O-beta-D-xylopyranosyl-(1-->4)-chi-L-rhamnopyranosyl-(1-->2)- [chi-L
      arabinofuranosyl-(1-->3)]-beta-D-4-O-acetylfucopyranoside; 3-O-[beta-D
      galactopyranosyl-(1-->2)-beta-D-glucuronopyranosyl] gypsogenin 28-O-beta-D
      xylopyranosyl-(1-->4)-chi-L-rhamnopyranosyl-(1-->2)- [chi-L-arabinofuranosyl (1-
      >3)]-beta-D-4-O-acetylfucopyranoside; and 3-O-[beta-D-galactopyranosyl-(1-->2)
      beta-D-glucuronopyranosyl] 3beta,4chi-dihydroxy-23norolean-12-en-28-oic acid 28-O
      beta-D-xylopyranosyl-(1-->4)-chi-L-rhamnopyranosyl-(1-->2) -chi-L
      arabinofuranosyl-(1-->3)]-beta-D-4-O-acetyfucopyranoside. Their structures were
      established on the basis of extensive NMR (DEPT, COSY, HOHAHA, HETCOR, HMBC AND
      NOESY), FAB-MS and ESI-MS studies as well as chemical strategies and enzymatic
      degradation. The new aglycones of two of the saponins have been designated as
      segetalic acid and vaccaric acid, respectively.

PMID- 9654780
TI  - Three phenylethanoid glycosides and an iridoid glycoside from Picrorhiza
      scrophulariiflora.
AB  - Three new phenylethanoid glycoside, named scrosides A-C and a new iridoid
      glycosides, named picroside IV, have been isolated from the underground parts of
      Picrorhiza scrophulariiflora, together with 11 known compounds. Their structures
      were elucidated by the means of 2D NMR spectroscopy and chemical methods.

PMID- 9654781
TI  - Emergence of collective strategies in a prey-predator game model.
AB  - The emergence of collective strategies in a prey-predator system is studied. We
      use the term "collective" in the sense of the collective motion of defense or
      attack often found in behaviors of animal groups. In our prey-predator system,
      both prey and predators move around on a two-dimensional plane, interacting by
      playing a game; predators can score by touching the backside of a prey.
      Thresholds are assumed for the scores of both prey and predators. The species
      with the higher scores can reproduce more, and that with the lower scores will be
      diminished. As a result, strategies as collective motions are observed; these
      consist of rotating cluster motions, line formations, disordered but one-way
      marching, and random swarming. In particular, the strategy of random swarming
      encourages symbiosis in the sense that it is associated with a low extinction
      probability for the whole system.

PMID- 9654782
TI  - An ecology of text: using text retrieval to study alife on the net.
AB  - I introduce a new alife model, an ecology based on a corpus of text, and apply it
      to the analysis of posts to USENET News. In this corporal ecology posts are
      organisms, the newsgroups of NetNews define an environment, and human posters
      situated in their wider context make up a scarce resource. I apply latent
      semantic indexing (LSI), a text retrieval method based on principal component
      analysis, to distill from the corpus those replicating units of text. LSI arrives
      at suitable replicators because it discovers word co-occurrences that segregate
      and recombine with appreciable frequency. I argue that natural selection is
      necessarily in operation because sufficient conditions for its occurrence are
      met: replication, mutagenicity, and trait/fitness covariance. I describe a set of
      experiments performed on a static corpus of over 10,000 posts. In these
      experiments I study average population fitness, a fundamental element of
      population ecology. My study of fitness arrives at the unhappy discovery that a
      flame-war, centered around an overly prolific poster, is the king of the jungle.

PMID- 9654783
TI  - A robot trace maker: modeling the fossil evidence of early invertebrate behavior.
AB  - The study of trace fossils, the fossilized remains of animal behavior, reveals
      interesting parallels with recent research in behavior-based robotics. This
      article reports robot simulations of the meandering foraging trails left by early
      invertebrates that demonstrate that such trails can be generated by mechanisms
      similar to those used for robot wall-following. We conclude with the suggestion
      that the capacity for intelligent behavior shown by many behavior-based robots is
      similar to that of animals of the late Precambrian and early Cambrian periods
      approximately 530 to 565 million years ago.

PMID- 9654784
TI  - EUZONE: simulating the evolution of aquatic ecosystems.
AB  - In the spirit of contemporary artificial life research, EUZONE provides a virtual
      laboratory for the emergence of complex ecosystems from simple primitives.
      However, whereas most alife systems abstract away many real-world environmental
      constraints, EUZONE employs detailed physical and chemical models in combination
      with evolutionary algorithms to support the emergence of carbon-based aquatic
      ecosystems. With an emphasis on plankton-like organisms, this research focuses
      upon the self-organization and evolution of (a) lower levels of aquatic food
      webs, (b) Gaian interactions between primitive organisms and their physical
      environments, and (c) species interactions governed by varying life-history
      strategies.

PMID- 9654785
TI  - 1997 declaration of the environment leaders of the Eight on children's
      environmental health.
AB  - On May 5-6, 1997, Administrator Carol M. Browner hosted the Environment Leaders'
      Summit of the G7 countries plus Russia, known as "the Eight," in Miami, Florida.
      Children's Environmental Health was the centerpiece topic for discussion at the
      Summit, which resulted in the 1997 Declaration of the Environment Leaders of the
      Eight on Children's Environmental Health and its annexed Implementation Actions
      on Protecting Children's Health and Environment Which the Environment Leaders of
      the Eight Have Agreed to Promote Within Their Governments and Countries. These
      documents provide a framework for domestic, bilateral and international efforts
      to improve the protection of children's health from environmental threats and
      specify concrete actions that the Eight will undertake to begin the process of
      incorporating characteristics of infants and children into environmental science,
      risk assessments and protection regimes.

PMID- 9654786
TI  - Children are different: environmental contaminants and children's health.
AB  - Although the impact of environmental contaminants on human health has been widely
      studied, few reports in the Canadian literature have focussed on the specific
      vulnerability of children. Because of their rapid growth, physiologic and
      metabolic immaturity, the fetus and child are often at increased risk from toxic
      substances in their environments. Furthermore, greater air, food and fluid
      intakes relative to body weight compared with the adult, increase the child's
      potential for excessive exposures. The crawling stage of infancy, the play
      patterns and short stature of toddlers also serve to increase their exposure to
      dust and heavy and volatile substances which accumulate near the floor. This
      article provides an overview of some of the developmental physiologic, anatomic
      and behavioural features of the fetus, infant and child which increase their
      vulnerability to environmental contaminants in comparison with adults. Specific
      examples are given.

PMID- 9654787
TI  - The case for child development as a determinant of health.
AB  - The complex relationship between life course and social/economic-psychosocial
      conditions in a given society has a powerful determining effect on human health.
      The socioeconomic gradient emerges from a complex mixture of psychosocial and
      material influences operating at various levels of social aggregation and, also,
      a series of biological responses whose character and significance vary over the
      life course. Biological embedding and the "latency" and "pathways" model
      incorporate the notion of a critical period in development; the pathways model
      emphasizes the cumulative effect of life events and the ongoing importance of
      social/economic-psychosocial conditions throughout the life cycle. The models,
      although conceptually complementary, result in ideological conflict and lend
      themselves to different policy directions.

PMID- 9654788
TI  - Prenatal exposure of Canadian children to polychlorinated biphenyls and mercury.
AB  - This article documents the exposure to environmental contaminants within sub
      groups of the Canadian population who are considered to be at risk as a result of
      the food they eat. We measured the concentrations of polychlorinated biphenyls
      (PCBs) and mercury in the blood drawn from the umbilical cords of newborns in
      various Aboriginal communities, in a coastal community and in the general
      population. Average concentrations of Aroclor 1260 ranged between 0.3 and 2.0
      micrograms/L and were clearly highest among the Inuit of Nunavik and Baffin
      Island and among the Montagnais of Quebec. In these groups, we found contaminant
      levels in the blood of newborns that exceed the threshold beyond which cognitive
      impairments are expected to result. Average concentrations of mercury ranged
      between 1.0 and 14.2 micrograms/L; the Inuit of Nunavik and the NWT exhibited the
      highest exposure levels. A portion of the Nunavik and NWT Inuit had
      concentrations beyond the critical threshold for the appearance of neurological
      consequences. The variations in exposure levels resulted from the different
      nutritional practices of these Canadian sub-groups.

PMID- 9654789
TI  - Child health, poverty and the environment: the Canadian context.
AB  - In Canada, there has been little research exploring the link between child
      poverty and exposure to environmental contaminants. However, children living in
      poverty are more likely to grow up in neighbourhoods adjacent to polluting
      industries and heavily used transportation corridors. They are also more likely
      to live in improperly designed or maintained buildings where levels of
      contaminants and toxic residuals may be high, and indoor air quality poor. Risk
      factors such as exposure to cigarette smoke and poor nutritional status, together
      with the above living conditions during growth and development, create conditions
      that make children living in poverty more vulnerable to the effects of
      environmental contaminants. In Toronto, the South Riverdale Community Health
      Centre is developing grassroots techniques to build awareness and protect
      citizens. Given the growing levels of child poverty in Canada and decreasing
      environmental protection, the author suggests increased community action and
      health research for use in advocating for appropriate policy changes.

PMID- 9654790
TI  - Issues in developmental neurotoxicology: interpretation and implications of the
      data.
AB  - The potential for environmental contaminants to produce neurological, cognitive,
      or other behaviour deficits as a result of developmental exposure has received
      increasing attention. The focus has shifted from description of frank
      neurotoxicity observed in a relatively few individuals to more subtle impairment
      in a much greater number of children. With this shift has come the recognition
      that subtle deficits such as a small decrease in IQ can have important societal
      impact when large numbers of children are affected. For example, the result of a
      1 microgram/dL decrease in blood lead concentration in children in the United
      States with blood lead concentrations between 10 and 20 micrograms/dL would
      translate into a savings of 5-7.5 billion U.S. dollars a year in increased
      earning power alone. In addition, behavioural problems such as increased
      aggression and poor social adjustment identified early in childhood may escalate
      to serious antisocial behaviour such as delinquency as the child approaches
      puberty. Exposure to neurotoxic agents during development or over a significant
      portion of the lifespan may also result in acceleration of age-related
      neurodegenerative diseases. Such changes in the functional abilities of a
      significant proportion of a population have potentially serious consequences for
      society as well as for affected individuals.

PMID- 9654791
TI  - Endocrine disruptors and development of the reproductive system in the fetus and
      children: is there cause for concern?
AB  - Reports of decreased semen quality and increased rates of developmental
      abnormalities of the male reproductive tract along with increasing incidence of
      testicular cancer have focused attention on man-made chemicals as potential
      causative factors. A biologically plausible hypothesis has been advanced which
      suggests that man-made chemicals act as endocrine disruptors through interaction
      with the estrogen receptor resulting in altered development of the reproductive
      tract. Available evidence suggests that this mechanism may play only a minor role
      in the purported adverse effects described to date. Man-made chemicals, however,
      may induce adverse health effects through mechanisms independent of the estrogen
      receptor. Indeed, man-made chemicals have been shown to induce adverse effects on
      thyroid function and androgen-dependent processes in animal studies. Hence the
      focus on estrogenic mimics may be too simplistic and alternate mechanisms could
      be more relevant due to target gland exposure levels and potency of the toxicant.
      Before it can be concluded that man-made chemicals pose little or no risk to the
      development of the reproductive tract in the fetus and children it will be
      necessary to, at the very least, insure that: 1) exposure scenarios include the
      most sensitive developmental stage, 2) all endocrine targets have been evaluated
      for potential effects, and 3) the role of environmentally and biologically
      relevant levels of chemical mixtures in adverse health outcomes have been
      evaluated. Due to potential for exposure, sensitivity of the developing
      reproductive tract, suggestive evidence of a possible role of man-made chemicals
      in developmental abnormalities of the reproductive tract, and the many
      outstanding research questions, it is concluded that there is sufficient cause
      for concern.

PMID- 9654792
TI  - Air pollution exposures and children's health.
AB  - The evidence from a large number of studies indicates that exposures to current
      outdoor air pollution increase respiratory morbidity in children. Children with
      asthma, and those with asthma-like symptoms but without a diagnosis of asthma,
      are considered to be at highest risk of experiencing short-term and/or longer
      term adverse health effects. Many outdoor air pollutants readily penetrate
      indoors. Indoor air quality can deteriorate quickly when persistent and
      uncontrolled emissions occur and the ventilation/air exchange rate is reduced. It
      has been estimated that children spend 90% of their time indoors, including in
      school buildings, vehicles and public indoor environments. Environmental tobacco
      smoke is a well-recognized persistent indoor air contaminant with adverse health
      effects in children of all ages. Uncontrolled moisture in the indoor environment
      is increasingly recognized to significantly increase the risk of respiratory
      morbidity in children. The evidence that air pollutants singly and in combination
      with other environmental factors elicit adverse health responses in asthmatic and
      non-asthmatic children and adolescents, appears irrefutable.

PMID- 9654793
TI  - The impact of PCBs and dioxins on children's health: immunological
      considerations.
AB  - Environmental contaminants include the potentially toxic metals lead, cadmium and
      mercury; the chlorinated pesticides mirex, toxaphene and hexachlorobenzene;
      chlorinated dioxins and furans; polyaromatic hydrocarbons; and polychlorinated
      biphenyls. While many of these chemicals are resistant to degradation in the
      natural environment, they dissolve readily in oils and thus accumulate in the
      fatty tissues of fish, birds and mammals. Human exposure is predominantly through
      the ingestion of contaminated food. An array of toxic effects including effects
      on the immune system have been described in experimental animals and in humans
      accidentally exposed to these chemicals. Such studies suggest that the immune
      system of the developing fetus and the newborn is particularly vulnerable to the
      toxic effects of chemicals. To fully appreciate the magnitude of risk these
      chemicals pose to children's health, there is a need for additional carefully
      focussed epidemiologic and mechanistic studies.

PMID- 9654794
TI  - Childhood cancer and environmental contaminants.
AB  - This article reviews the available epidemiologic evidence for relationships
      between the development of cancer in childhood and environmental agents,
      specifically chemicals, ionizing radiation, low-frequency electromagnetic fields,
      and infectious agents. Chemical exposures include medications and other drugs,
      components of diet, and second-hand exposure to industrial chemicals and to
      environmental carcinogens. Ionizing radiation is the only well-established risk
      factor for childhood cancers. Suggestive associations with excess childhood
      cancer risk have been found with exposures to paints, petroleum products,
      solvents, pesticides and metals. An excess risk of brain tumours has been
      reported with ingestion of n-nitroso compounds, and there have been positive
      findings relating leukemia risk and infections. Studies of risk of childhood
      cancer with parental use of alcohol and with parental smoking have been generally
      negative, while the inconsistencies and generally low risks reported in studies
      of power-frequency electromagnetic fields do not support a causal relationship.

PMID- 9654795
TI  - Role of health professionals in protecting children from environmental risks: a
      commentary.
AB  - Health professionals are well positioned to protect children from environmental
      exposures to toxicants. Doing so may mean mobilizing for precautionary action
      well before conclusive evidence of adverse health impacts are documented in the
      community. This paper comments on the context within which health professionals
      work, and identifies strengths, barriers and guiding principles for action. Roles
      and strategies are identified for both medically and community-focussed health
      professionals. The prevention--treatment continuum (global action--policy and
      regulatory reform--local collective action--health protection--medical treatment)
      is explored. While health professionals traditionally deal with the treatment
      (downstream) end of the spectrum in addressing environmental health problems,
      there are ample opportunities for expanding this role to the prevention
      (upstream) end. Applicable strategies are organized into six major roles:
      surveillance, hazard assessment, research, education, public awareness, and
      advocacy. Advocacy is one of the most important roles since it involves upstream
      activities close to the source of the problem. While downstream endeavours have a
      legitimate place in the practice of health professionals, expanding this role to
      include upstream strategies, such as health promotion and advocacy, is essential
      if efforts to protect children's health are to succeed in the long term.

PMID- 9654796
TI  - Air pollution: the environmental phoenix.

PMID- 9654797
TI  - The effect of the urban ambient air pollution mix on daily mortality rates in 11
      Canadian cities.
AB  - OBJECTIVE: Determine the risk of premature mortality due to the urban ambient air
      pollution mix in Canada. METHODS: The number of daily deaths for non-accidental
      causes were obtained in 11 cities from 1980 to 1991 and linked to concentrations
      of ambient gaseous air pollutants using relative risk regression models for
      longitudinal count data. RESULTS: Nitrogen dioxide had the largest effect on
      mortality with a 4.1% increased risk (p < 0.01), followed by ozone at 1.8% (p <
      0.01), sulphur dioxide at 1.4% (p < 0.01), and carbon monoxide at 0.9% (p = 0.04)
      in multiple pollutant regression models. A 0.4% reduction in premature mortality
      was attributed to achieving a sulphur content of gasoline of 30 ppm in five
      Canadian cities, a risk reduction 12 times greater than previously reported.
      CONCLUSIONS: Ambient air pollution generated from the burning of fossil fuels is
      a risk factor for premature mortality in 11 Canadian cities.

PMID- 9654798
TI  - Car phones and car crashes: an ecologic analysis.
AB  - OBJECTIVE: Some countries have regulations against using a cellular telephone
      while driving. We used ecologic analysis to evaluate cellular telephone use and
      motor vehicle collisions in a city without such regulations. METHODS: We studied
      locations in Toronto, Ontario (n = 75) that were hazardous (total collisions =
      3,234) and tested whether increases in collision rates from 1984 to 1993
      correlated with increases in telephone usage over the same time interval.
      RESULTS: Locations with the largest increases in collision rates tended to have
      the smallest increases in estimated cellular telephone usage. Yet extreme
      assumptions about potential protective effects from cellular telephones failed to
      explain the magnitude observed. CONCLUSIONS: The effects of cellular telephones
      on driving ability are small relative to the biases in ecologic analysis. Claims
      from industry, which argue that cellular telephones are not dangerous based on
      ecologic analysis, can be misleading in the policy debate about whether to
      regulate cellular telephone use while driving.

PMID- 9654799
TI  - Knowledge, perception and behaviour of the general public concerning the addition
      of fluoride in drinking water.
AB  - A telephone survey was carried out in 1994, in the Quebec City region, among 1006
      people living in two municipalities where tap water is fluoridated and 1003
      people living in two municipalities where there is no fluoridation. Knowledge of
      the main benefit associated with the use of fluoride (prevention of tooth decay)
      in drinking water was not different in fluorated versus non-fluoridated
      municipalities (20.4% vs 19.4%, p = 0.57). Knowledge of its main disadvantage
      (increase of dental fluorosis) was very low and similar in both groups (3.1% vs
      2.0%, p = 0.11). Opposition to fluoridation was slightly higher in fluoridated
      areas (22.0% vs 18.3%, p = 0.04), and the use of fluoridated supplements for
      children was much less important in fluoridated areas (4.4% vs 12.4%, p = 0.001).
      No changes in the measures of association (odds ratios) were found after
      adjustment for the different characteristics of the participants (age, family
      income, education). Opposition to fluoridation was lower among those who believed
      their tap water was fluoridated (even if not): 19.9% vs 34.5%, p < 0.001. This
      study demonstrates that there is still need for public health education on the
      uses of fluorides.

PMID- 9654800
TI  - One year outcome evaluation of an alcohol and drug abuse prevention program in a
      Quebec high school.
AB  - This article presents the results of a one-year outcome evaluation of a school
      based alcohol- and drug-abuse prevention program targeting adolescents in Quebec.
      This evaluation concerns the school component of the program and includes the
      first seven classroom interventions. The design is a pre- and post-intervention
      assessment of both the experimental (n = 145 students) and the control school (n
      = 179 students). Results obtained do not reveal any significant effect of the
      program on knowledge and beliefs regarding the use of alcohol and drugs, or any
      modification in self-efficacy with respect to decision making and ability to
      resist external pressure concerning the decision to use marijuana/hashish. The
      results do show, however, a decrease among the exposed students in self-efficacy
      within the context of alcohol use. Such a result may be a consequence of the
      program's capacity to raise the students' level of awareness of their
      susceptibility to social influences. It is plausible that in order to have
      positive effects, classroom interventions such as the present one need to be
      supplemented by additional activities targeting youths' environment.

PMID- 9654801
TI  - A cardiovascular health needs assessment of university students living in
      residence.
AB  - The purpose of this study was to determine the cardiovascular health needs of
      university students living in residence. A survey was administered to students
      living in residence at a university in Nova Scotia, Canada to identify eating
      patterns, physical activity, smoking behaviours and perceived stress. Data were
      analyzed using descriptive statistics and chi-square tests of association.
      Qualitative data were collected using focus group interviews. Results showed that
      fewer than half of the students participated in exercise three or more times per
      week, and 82% are less than the recommended amount of fruits and vegetables. As
      perceived knowledge of CVD increased so did level of physical activity and
      consumption of fruits and vegetables. Fifty-six percent of students rated their
      stress as high or very high; exams and course assignments are a major cause of
      this stress. Fifteen percent of the university students surveyed were daily
      smokers. Barriers to a healthy lifestyle include time constraints and limited
      food choices in the residence cafeteria.

PMID- 9654802
TI  - [Effectiveness of an educational intervention in improving the self concept of
      second to sixth grade students].
AB  - This study evaluated the effectiveness of an intervention in improving the
      general, academic, physical and social self-concepts of 2nd to 6th grade
      students. The activities were carried out by the teachers during the 1992-93
      school year. A questionnaire was completed by 271 students of the experimental
      school and by 467 students of the control school, both before and after the
      intervention. The multiple regression analyses showed important adjusted gains
      for self-concepts related to physical appearance, mathematics and relationship
      with parents. In all three cases, students with the largest deficit benefitted
      most from the intervention. This study shows that it is possible to improve self
      concept and to do so through an intervention carried out in the school
      environment. This double finding is important to the promotion of psycho-social
      adaptation since self-concept is an important determinant and since few
      interventions have reached similar objectives.

PMID- 9654803
TI  - Gender differences in the prevalence of depression among Canadian adolescents.

PMID- 9654804
TI  - [Evaluation and validation of a test of psychological distress in a general
      population in french Quebec].
AB  - Psychological distress scales used in epidemiologic surveys usually show high
      construct validity. The content validation however is less convincing since these
      scales rest on lists of psychiatric symptoms which are hypothesized as the very
      content of a psychological distress. This study presents the results of the
      construct and criterion validation of a new Psychological Distress Manifestations
      Measure Scale (PDMMS) founded on an initial list of manifestations derived from
      an original content validation in a general population. Twenty-three items are
      grouped in four oblique factors with Cronbach's alpha ranging between 0.81 and
      0.89. High scores on the scale are correlated with psychoactive drugs
      consumption, visits to health professionals and self-evaluations of psychological
      health.

PMID- 9654805
TI  - Alberta's infant mortality rate: the effect of the registration of live newborns
      weighing less than 500 grams.

PMID- 9654806
TI  - Diet survey of two cultural groups in a coastal British Columbia community.
AB  - OBJECTIVES: As part of a larger study of polychlorinated dibenzodioxin (PCDD) and
      dibenzofuran (PCDF) pollution, to describe and compare Aboriginal and non
      Aboriginal residents' recalled diets. METHODS: We surveyed a stratified random
      sample aged 25 to 64 years: forest products mill employees (n = 84), Aboriginal
      reserve residents (n = 78), and other residents (n = 80). We administered a
      questionnaire on intake of fish/seafood, wild game and plants, domesticated
      animal meat and eggs, dairy products, vegetable oils and cereals; age, gender,
      childbearing, lactation, residence and smoking. We measured height and weight.
      RESULTS: Reserve residents ate less seafood, but more fish roe, eulachon grease,
      smoked salmon, clams and sea urchins, more deer organs, hamburger meat, pork,
      fried chicken, and hot-dogs, but less rabbit, beef steaks/roasts, high-fibre
      cereals, potato chips, bread, cheese and milk. CONCLUSIONS: We cannot yet
      quantify PCDD and PCDF intakes. The wild food consumption data are unique and may
      be useful for risk assessments in the target population and similar communities.

PMID- 9654807
TI  - Effectiveness of public health interventions in food safety: a systematic review.
AB  - PURPOSE: To summarize evidence on the effectiveness of public health
      interventions regarding food safety at restaurants, institutions, homes and other
      community-based settings. METHOD: This systematic review of published and
      unpublished studies involved a comprehensive literature search, screening for
      relevance, quality assessment of relevant studies, data extraction and synthesis.
      RESULTS: The interventions identified in 15 studies included in this review were
      grouped into three categories: inspections, food handler training, and community
      based education. The evidence suggests that: routine inspection (at least once
      per year) of food service premises is effective in reducing the risk of foodborne
      illness; food handler training can improve the knowledge and practices of food
      handlers; and selected community-based education programs can increase public
      knowledge of food safety. DISCUSSION: There is some evidence for the
      effectiveness of multiple public health interventions on food safety. Future
      research needs include evaluation of HACCP and community-based education
      programs.

PMID- 9654808
TI  - Influences on breastfeeding rates in low income communities in Ontario.
AB  - The purpose of this paper was to identify factors associated with breastfeeding
      among mothers of children born in 1994 in five of the low income communities
      participating in the longitudinal prevention initiative "Better Beginnings,
      Better Futures." Household income was < or = poverty line for 76%, 63% had
      completed high school or beyond, and 29% were born outside of Canada. The
      breastfeeding initiation rate was 77% (380 of 493). Of the 270 women who
      initiated breastfeeding and were interviewed up to five months postpartum, 63%
      continued for at least three months. Women with higher education, married, not
      experiencing financial stress and who attended prenatal classes were more likely
      to initiate breastfeeding. Continuation of breastfeeding was associated with
      older age, higher education, not smoking, and participation in a home visitor
      program. Breastfeeding promotion strategies should include ongoing support as
      well as education components.

PMID- 9654809
TI  - Socioeconomic position. Lifestyle and health among Canadians aged 18 to 64: a
      multi-condition approach.
AB  - Although a sizeable literature documents the link between socioeconomic position
      and health in Britain and the United States, much less work has been conducted in
      Canada. Moreover, what work has been done has been limited to single outcomes
      such as self-rated health or age-adjusted mortality. Very little has been
      conducted using multiple health outcomes, although doing so has been advocated.
      Using the 1991 General Social Survey on Health, we extended an earlier analysis
      to explore whether or not "condition-specific" relationships exist between
      socioeconomic position, lifestyle, and health among working age Canadians. We
      distinguished four patterns in terms of education and income adequacy. The
      effects of occupation did not fit into any simple pattern. Measures of lifestyle
      appear to mediate the relationship between education and morbidity, but not
      between income adequacy and morbidity. Findings are discussed in terms of the
      theoretical, methodological and policy implications of a condition-specific
      approach.

PMID- 9654810
TI  - Hope suspended: morality, politics and war in central Africa.
AB  - The Great Lakes tragedy from 1994-8 has demonstrated the impact of a new
      consensus in favour of conditional relief for the protection and assistance of
      disaster victims. This paper attempts to catalogue the failures of the
      international humanitarian community, African leaders and donor governments to
      act effectively in defence of humanitarian principles throughout the crisis. The
      paper places special emphasis on the events in eastern Zaire during 1996-7 that
      have, so far, received limited treatment, and, it contends, led to the loss of
      hundreds of thousands of lives. The paper argues that the new orthodoxy of
      developmental relief, as adopted by UN and NGO humanitarian agencies in the Great
      Lakes, has acted more in support of the geopolitical and economic agendas of
      Northern governments and African leaders than in defence of disaster victims. The
      paper points out that the evidence of the Great Lakes tragedy suggests that the
      adoption of these approaches has sanctioned the abandonment of ideas about
      universal rights of protection for non-combatants at the moment when they are
      most at risk, with catastrophic results for those most vulnerable to abuse.

PMID- 9654811
TI  - Cool ground for aid providers: towards better security management in aid
      agencies.
AB  - Although full statistics are lacking, there is an impression that aid personnel
      are increasingly at risk from random, criminal and even at times targeted
      violence. The argument here is that the current tendency to reduce an agency's
      vulnerability mainly through the use of protective procedures and devices may be
      necessary but is insufficient. Better practice in the management of security is
      an urgent need. Reducing vulnerability to attack is only one approach; deterring
      the threat of violence by counter-threat, or seeking increased acceptance for the
      agency's work and presence are two other approaches. Major skill development is
      required in the areas of conflict analysis and monitoring, threat assessment and
      incident analysis, since together these form the basis for appropriate security
      management. Improved analysis can then inform a conscious choice about which
      mixture of approaches is most appropriate in a specific context. The paper
      explores in some detail the factors that influence acceptance, but not the
      methods and basic principles in the use of counter-threat.

PMID- 9654812
TI  - Making women visible in disasters: problematising the private domain.
AB  - Gender awareness and sensitivity in disaster research and management remains
      uncommon and tends to focus on the developing rather than the developed world.
      This paper uses a feminist oral geography to present some findings about women's
      experiences in two floods in Scotland. It is conceptualised around public and
      private (masculinised and feminised) space, problematising the private domain and
      presenting it, in the feminist research tradition, as a legitimate object of
      research. It shows the ordinary and everyday to be more opaque and complex than
      usually imagined and makes recommendations for their recognition and
      incorporation into disaster management. While there is a specific focus on the
      private domain of the home, this is not intended to reinforce gender stereotypes
      but simply to recognise the reality of many of the women interviewed. It
      concludes that disaster research generally has yet to advance much beyond the
      earliest stages of feminist studies which merely sought to make women visible in
      society.

PMID- 9654813
TI  - A review of contributions to disasters: 1977-1996.
AB  - Since the first issue in 1977. Disasters has been one of the pre-eminent refereed
      journals on the study and reporting of disasters. This article reviews 703
      articles and reports in the journal through 1996 to provide a snapshot of the
      nature of the journal throughout 20 years of publication. The results indicate
      the most common contributions: first, were research articles by authors from the
      North Atlantic; second, most often dealt with natural disaster relief or impact;
      and third, most frequently focused on Africa. These generalisations, however, do
      not reflect attention paid to food-related and political disasters and greatly
      understate the broad diversity of material presented in the journal. To improve
      the topical and geographic coverage of Disasters probably requires a proactive
      effort to close gaps in the journal's coverage of disasters.

PMID- 9654814
TI  - Through women's eyes: a gendered research agenda for disaster social science.
AB  - Gender is a central organising principle in social life and hence in disaster
      affected communities, yet gender issues are rarely examined by disaster scholars
      or practitioners. Building on findings from emerging and industrial nations,
      three key research directions are identified: How is gendered vulnerability to
      disaster constructed? How do gender relations shape the practice of disaster
      planning and response in households and organisations? How are gender relations
      affected over time by the social experience of disaster? The discussion suggests
      how analysis of the gendered terrain of disaster both develops disaster theory
      and fosters more equitable and effective disaster practice.

PMID- 9654815
TI  - The disaster-to-development continuum.

PMID- 9654816
TI  - Lung volume reduction surgery.

PMID- 9654817
TI  - Clinical presentation of tuberculosis in patients with AIDS: an Indian
      experience.
AB  - A retrospective series of 25 patients with AIDS and tuberculosis is presented.
      Their clinical presentation, absolute lymphocyte count, CD4+ and CD8+ lymphocyte
      counts, treatment details and outcome are detailed. Commonest method of acquiring
      HIV infection was through heterosexual contact (10 of the 25; 40%) and blood
      transfusion (10 of the 25; 40%). More than 50% of the patients (14 of the 25) had
      extrapulmonary tuberculosis. Eighteen of the 19 patients for whom values were
      available had CD4+ lymphocyte count < 200/mm3. Four of the 18 patients for whom
      follow-up details were available died.

PMID- 9654818
TI  - Bronchial carcinoid tumours in southern Saudi Arabia.
AB  - Clinical presentation, pathology, surgical management and follow-up of ten
      bronchial carcinoid tumour (BCT) patients are described. There were five male and
      five female patients with age range between 5 to 85 years (mean 39.2 +/- 21.5,
      SD). Pathology revealed BCT on the right side in seven and on left side in three
      patients. The tumour was an incidental finding in four while the other six had
      respiratory symptoms. Cough was present in all of the later group and hemoptysis
      was present in four patients. Recurrent chest infections were seen in two
      patients. Symptoms ranged from 1 week to 15 years. Successful surgical resection
      was done in nine with the longest follow-up of 80 months (mean: 23 months +/-
      26.3, SD) without recurrence or metastasis. Histopathological examination of
      these tumours revealed classical morphological features in all but one case.
      Grimelius stain positivity for argyrophilia confirmed the diagnosis in all the
      patients in this study. Electron microscopic examination was done in patient no.
      9 which showed atypical morphological features and neurosecretory granules. BCT
      may present like pneumonias or bronchial asthma. Although BCTs have low-grade
      malignancy, early diagnosis and surgical resection yield curative results almost
      in all cases.

PMID- 9654819
TI  - Mediastinal bronchogenic cysts.
AB  - It was observed from the literature that the incidence, clinical and radiological
      features of the mediastinal bronchogenic cysts are different in adults than in
      infant population. Five cases of bronchogenic cysts in the middle mediastinum
      were studied over a period of 22 years. The cysts were carina-based in four cases
      and paratracheal in one case. The airway compression was observed in four cases
      due to cysts. In case one the cyst compressed the right pulmonary artery and vein
      as well as both mainstem bronchi causing their stenosis and bulged into the left
      atrial chamber.

PMID- 9654820
TI  - An analysis of effect of common domestic fuels on respiratory function.
AB  - Pulmonary function studies were carried out in 3318 healthy, nonsmoking
      asymptomatic housewives to evaluate the role of different cooking fuels in
      domestic use. The women used four different types of cooking fuels: biomass fuel,
      liquified petroleum gas (LPG), kerosene used in stoves, and a combination of two
      or more of these (mixed). Four parameters of ventilatory function (FVC, FEV1,
      PEFR and MMEF) were evaluated. A positive correlation was observed between all
      these parameters except PEFR with that of height, but a negative correlation was
      observed between the age, duration of cooking and exposure index. Mixed fuels and
      biomass fuels affected FVC values (F = 6.39, p = 0.0003) more adversely. Similar
      trend was observed for FEV1 also. Users of biomass fuel had the lowest mean value
      for PEFR. Small airways function represented by MMEF was the lowest in users of
      kerosene. In users of mixed fuels, there was a decline in FVC, FEV1 and PEFR, as
      the exposure increased. Thus, it is concluded that, mixed fuel has more
      deleterious effects on pulmonary function than other fuels.

PMID- 9654821
TI  - Bilateral miliary pattern in sarcoidosis.

PMID- 9654822
TI  - Endobronchial tuberculosis simulating lung cancer.
AB  - We describe an atypical presentation of endobronchial tuberculosis in a 45-year
      old female who presented to us with a non-resolving pneumonia. Her radiological
      examination including contrast enhanced CT-scan suggested a diagnosis of
      bronchogenic carcinoma or adenoma. Gross bronchoscopic finding also favoured
      malignancy. But her bronchoscopic biopsy revealed caseating granulomatic lesion.
      She responded to antitubercular treatment.

PMID- 9654823
TI  - Acute isoniazid poisoning: presenting as seizure.
AB  - A case of young female who was brought in status epilepticus with history of
      isoniazid poisoning is discussed. Early institution of treatment with pyridoxine
      saves the patient's life.

PMID- 9654824
TI  - Non-Hodgkin's lymphoma masquerading as empyema thoracis.
AB  - Non-hodgkin's lymphoma has varied presentations. Malignant lymphoma arising in
      chronic pyothorax is very rare and has been reported from Japan. We report a case
      of non-hodgkin's lymphoma presenting as empyema thoracis.

PMID- 9654825
TI  - Pulmonary alveolar microlithiasis: diagnosed by sputum examination and
      transbronchial biopsy.
AB  - A case of pulmonary alveolar microlithiasis presenting with uncharacteristic
      radiological features who was diagnosed on the basis of sputum examination and
      confirmed by transbronchial biopsy, is being reported. Azoospermia resulting in
      primary infertility and increased lung volumes by helium dilution test were other
      noteworthy features of the case.

PMID- 9654826
TI  - Antibiotic use for infective terminal respiratory secretions.

PMID- 9654827
TI  - Re: Cancer pain emergencies.

PMID- 9654828
TI  - Antiemetic efficacy of subcutaneous 5-HT3 receptor antagonists in terminal cancer
      patients.

PMID- 9654829
TI  - Thioridazine in the management of cancer-related sweating.

PMID- 9654830
TI  - Re: A randomized controlled trial of Intravenous clodronate.

PMID- 9654831
TI  - Dextropropoxyphene acts as a noncompetitive N-methyl-D-aspartate antagonist.
AB  - In order to elucidate whether opioid analgesics available on the Scandinavian
      market also act as noncompetitive N-methyl-D-aspartate (NMDA) antagonists, a
      series of commercially available opioids were screened for their affinity in
      [3H](RS)-5-methyl-10, 11-dihydro-5H-dibenzo[a,d]cycloheptene-5,10-imine ([3H]MK
      801) binding assays and potential inhibitory actions on responses to NMDA in the
      rat cortical wedge preparation. Of the screened compounds (codeine,
      dextropropoxyphene, etorphine, fentanyl, and morphine), only dextropropoxyphene,
      with an IC50 value in [3H]MK-801 binding of 5 microM, was found to be active.
      Further characterization of the interaction of dextropropoxyphene with the NMDA
      response in the rat cortical wedge preparation illustrated the noncompetitive
      NMDA antagonist activity of dextropropoxyphene. Analysis of the
      dextropropoxyphene inhibition curve of NMDA gave an IC50 value of 190 microM and
      a Hill slope of 0.8.

PMID- 9654832
TI  - Cancer pain survey: patient-centered issues in control.
AB  - It is widely believed that patients' reluctance to report pain and adhere to
      treatment recommendations are significant barriers to cancer pain control.
      However, few investigators have examined barriers to cancer pain management from
      the cancer patient's perspective. Ambulatory patients with cancer who had
      experienced cancer-related pain in the previous month or were currently taking
      analgesics for cancer pain control were asked to participate in this study.
      Information regarding (a) pain assessment, (b) pain medication use, (c) concerns
      and barriers to compliance, (d) communication patterns regarding pain and pain
      control, and (e) demographics were collected during a 10-min structured
      interview. Approximately 20% of patients with a current cancer diagnosis who were
      approached reported that they had experienced pain or taken analgesic drugs
      during the preceding month. Eighty-eight percent of these patients ranked their
      pain as five or greater (scale, 0-10), and 81% reported impaired function due to
      pain. Major barriers to effective treatment included forgetfulness, the belief
      that pain should be tolerated, concerns about side effects, and fear and disdain
      of dependence, addiction, and tolerance. One-third of patients felt that their
      pain could not be better controlled than it currently was. Patients reported
      frequent communication regarding pain and pain control with physicians (52%),
      nurses (41%), and pharmacists (17%). The low pain prevalence, coupled with high
      pain intensity and associated dysfunction, appears to be a reflection of
      patient's unwillingness to report pain of mild to moderate intensity. In addition
      to previously recognized factors, stoicism and fatalism represent significant
      barriers to cancer pain control.

PMID- 9654833
TI  - The prevalence and severity of cancer pain: a study of newly-diagnosed cancer
      patients in Taiwan.
AB  - Cancer pain is a relatively neglected public health issue in Taiwan. To
      characterize the nature of this problem, interviews were conducted on newly
      diagnosed cancer patients admitted to the Tri-Service General Hospital during a
      period of 18 months. Data were collected on the prevalence and severity of cancer
      pain, its treatment, and impact on patients in the week before the interview.
      Correlates of prevalence and severity of cancer pain were also examined. The
      final analysis included 296 patients who had no history of recent surgery. Most
      of the patients (69%) were interviewed within 14 days of their definitive
      diagnosis of cancer. Thirty-eight percent (N = 113) of the patients had cancer
      related pain. Of these 113 patients, 65% had "significant worst pain" (worst pain
      level at or above five on a ten-point scale) and 31% had "significant average
      pain" (average pain level at or above five most of the time); 69% received no
      pain medication at all or inadequate medication (not "by the ladder"), and 23%
      had pain medication that was not administered at a fixed interval (not "by the
      clock"). Multivariate analyses showed that cancer pain was more prevalent in non
      Mainlanders, those with a lower level of insurance, those with a history of
      excellent pain tolerance, those with poor Eastern Cooperative Oncology Group
      (ECOG) performance status, and those with distant metastases. Patients who were
      at greater risk of "significant worst pain" were those with regional or distant
      metastases, those in whom an inadequate analgesic medication had been prescribed
      (not "by the ladder"), and those who had received an appropriate analgesic
      medication but no fixed schedule dosing ("by the ladder" but not "by the clock").
      Patients who were at greater risk of "significant average pain" were those not
      undergoing any resection of the tumor lesion and those who received an
      appropriate drug but no fixed schedule dosing ("by the ladder" but not "by the
      clock").

PMID- 9654834
TI  - Development of a short version of the Barriers Questionnaire.
AB  - Among the reasons that cancer pain is not controlled adequately are patient
      related barriers. Patient beliefs that may contribute to poor outcome have been
      measured in previous research with the Barriers Questionnaire (BQ). The purpose
      of this study was to examine the internal consistency of a shortened version of
      the BQ. A sample of 217 outpatients with cancer completed a 17-item version of
      the scale. Factor analysis suggested two subscales, one reflecting beliefs about
      communication about pain and the other reflecting beliefs about the use of
      analgesics. Both subscales demonstrated adequate internal consistency. Beliefs
      did not differ between patients who had and those who had not experienced pain
      within the previous two weeks. Findings suggest the shortened BQ provides an
      internally consistent measure of two broad patient barriers to pain management.

PMID- 9654835
TI  - Drug infusors in palliative medicine: a Swedish inquiry.
AB  - The use of drug infusors is common in palliative care. Knowledge about the drugs
      being used and the handling of drug mixtures in insufficient and poorly
      documented. To clarify this practice, a questionnaire was sent to all departments
      of pain/anesthesiology and oncology, and to all home-care teams and palliative
      care units/hospices in Sweden (N = 156). The questions concerned specific
      qualities of the drug infusors and the different drugs and drug mixtures used by
      subcutaneous (s.c.) and intravenous (i.v.) administration. A total of 110 (70%)
      of the questionnaires were returned. A majority of the respondents reported the
      use of one or more of three different infusors. Morphine was used in 73% of all
      single drug infusions. Dosages ranged from 30 mg/24 hr to 5000 mg/24 hr. The most
      common drug mixture was morphine/haloperidol (22% of all drug mixtures). As many
      as three drugs were used in combination. The most frequent indication to switch
      from oral administration to parenteral administration was gastrointestinal
      disorders such as swallowing difficulties, nausea, vomiting, or bowel
      obstruction. In Sweden, there is extensive clinical experience administering
      opioids in infusors, but experience varies for different drug mixtures. There are
      few clinical and pharmacological investigations to support this practice and
      further studies are needed.

PMID- 9654836
TI  - Pain and fear ratings: clinical implications of age and gender differences.
AB  - The study investigated the relationships among children's self-report of
      anticipatory pain and fear, physiological measures of distress, and previous
      medical experience in 62 outpatients during allergy skin testing. Younger (aged 3
      7 years) and older (aged 8-12 years) children reported similar amounts of pain
      and fear. Girls reported more pain than boys. Older children and boys provided
      differential pain and fear ratings compared with younger children and girls.
      Younger children's self-report of distress was not related to any physiological
      measures, but older children's report of fear was significantly related to blood
      pressure. In girls, positive medical experience was correlated with less pain.
      The implications of these findings for the clinical measurement and intervention
      of children's distress during painful medical procedures are discussed.

PMID- 9654837
TI  - Proglumide as a morphine adjunct in cancer pain management.
AB  - Proglumide, a cholecystokinin (CCK) antagonist, has been shown to have agonist
      effects at extremely low doses on both endogenous and exogenous opioid systems.
      To determine the effectiveness and the side effects of proglumide as an opioid
      agonist, a double-blind crossover study was conducted in 60 patients with cancer
      pain who were treated with opioid analgesics. Forty-three patients completed both
      treatment arms: (a) full analgesic dose plus placebo (the patient's usual
      analgesic dose, individualized to drug dose and route) and (b) one-half analgesic
      dose plus 50 mg of proglumide. An analysis of eight pain descriptors was
      performed to determine whether or not these treatments were associated with a
      difference in patients' pain perception. The level of patient anxiety differed
      between the two arms, but was inconsistent over time. There were no side effects
      detected with proglumide, as determined by clinical monitoring and patient
      questionnaire. No differences in pain perception were detected between the study
      arms. The latter finding is consistent with an augmentation of morphine
      analgesia, but without additional controls, the equivalency of the two arms
      cannot be determined with certainty. Nonetheless, this study suggests that
      proglumide may have use as an opioid adjunct in patients with cancer pain.

PMID- 9654838
TI  - Spinal accessory nerve palsy as a cause of pain after whiplash injury: case
      report.
AB  - Spinal accessory nerve injury is most commonly reported following surgery in and
      around the posterior cervical triangle. Pain, impaired ability to raise the
      ipsilateral shoulder, and scapular winging on abduction of the arm are the most
      frequently noted clinical manifestations. We report the case of a collegiate
      swimmer who developed left-sided neck and shoulder pain secondary to a spinal
      accessory nerve palsy (SANP) after a "whiplash injury," which we believe to be
      the first such reported case in the English language literature. We review the
      clinical manifestations, diagnostic pitfalls, and therapeutic approaches to SANP.
      A high index of suspicion for SANP following whiplash-type injury will ensure its
      earlier detection and treatment and improve the chances of a better functional
      outcome.

PMID- 9654839
TI  - FDA reform: implications for health economic research and pharmacy practice.

PMID- 9654840
TI  - Do we really need quality measures in community pharmacy?

PMID- 9654841
TI  - Computerized DUR alerts: boon or bane to pharmaceutical care?

PMID- 9654842
TI  - Medical marijuana: not the way the doctor would have ordered it.

PMID- 9654843
TI  - Medicinal marijuana: the California experiment.

PMID- 9654844
TI  - Integrated pharmacy services: cornerstone of a new model of care at celebration
      health.

PMID- 9654845
TI  - Pharmacy Practice Activity Classification.

PMID- 9654846
TI  - How pharmacists respond to on-line, real-time DUR alerts.
AB  - OBJECTIVE: To quantify the type and frequency of drug utilization review (DUR)
      alerts sent by one claims processor to pharmacists; identify how pharmacists
      respond to these on-line, real-time DUR messages; and quantify the interventions
      taken by these pharmacists as a result of these alerts. DESIGN: Retrospective
      analysis of Medicaid claims from July 1, 1995, through June 30, 1996. SETTING:
      State of Delaware. PARTICIPANTS: 55,000 Medicaid recipients served by 170
      participating pharmacies and 2,000 physicians. INTERVENTIONS: All on-line DUR
      alerts sent to pharmacists and the pharmacists' responses were categorized by
      alert type and analyzed by drug class. MAIN OUTCOME MEASURES: Pharmacists'
      response (dispensed prescription, contacted prescriber, talked with patient,
      consulted own reference sources) and drug classes. RESULTS: During the study
      period, 807,017 claims generated 83,260 DUR alerts involving 73,554 (9.1%)
      prescriptions. Prescriptions were not dispensed in 20.9% of cases because of the
      DUR message. Prescriptions were dispensed 17.7% of the time after the pharmacist
      contacted the prescriber, in 20.6% of cases after the pharmacist talked with the
      patient, and 37.2% of the time after reviewing internal resources. Action taken
      by pharmacists varied among and within DUR criteria categories. Specific examples
      of alerts generated in high-frequency and high-profile areas are reviewed, some
      of which generated inconsistent responses. CONCLUSION: Among Delaware Medicaid
      providers, drug alerts resulted in pharmacists not dispensing prescriptions in a
      surprising percentage of situations. Pharmacists' responses varied according to
      the drug class involved and the type of alert received.

PMID- 9654847
TI  - New drugs of 1997.
AB  - OBJECTIVE: To provide information regarding the most important properties of the
      new therapeutic agents marketed in 1997. DATA SOURCES: Published studies, drug
      information reference sources, and product labeling. DATA SYNTHESIS: A record
      setting number of 45 new therapeutic agents were marketed in 1997. The
      indications and information on dosage and administration for each new agent are
      reviewed, as are the most important pharmacokinetic properties, adverse events,
      drug interactions, and other precautions. Practical considerations for the use of
      the new agents are also discussed. Where possible, the properties of the new
      drugs are compared with those of older drugs marketed for the same indications.
      CONCLUSION: A number of the new therapeutic agents marketed in 1997 have
      important advantages over older medications. An understanding of the properties
      of these agents is important for the pharmacist to effectively counsel patients
      about their use and to serve as a valuable source of information for other health
      professionals regarding these drugs.

PMID- 9654848
TI  - New OTC drugs and devices 1997: a selective review.
AB  - OBJECTIVE: To create a heightened awareness of the proposals for nonprescription
      product labeling changes being explored by the Food and Drug Administration and
      the Nonprescription Drug Manufacturers Association, and to review selected new
      self-care products that are now available in the United States. DATA SOURCES:
      Recent clinical and pharmaceutical industry literature. DATA SYNTHESIS: The
      debate continues about what constitutes sufficient labeling information for a
      nonprescription drug product. However, one fact remains. Numerous nonprescription
      drug products, including home diagnostic products and accessories, will continue
      to become available on the U.S. market. It is important that the pharmacist
      become as knowledgeable as possible about these products, and be capable of
      educating consumers on their appropriate use. CONCLUSION: New products cited in
      this review article are valuable new additions to the self-care product pool that
      provides an increasing array of products for consumer use.

PMID- 9654849
TI  - Important features of blood glucose meters.
AB  - OBJECTIVE: To provide an overview of several blood glucose meters that will
      enhance practicing pharmacists' knowledge and understanding of these devices to
      allow education of the patient with diabetes. DATA SOURCES: Original and review
      articles, blood glucose meter package inserts and manuals. DATA SYNTHESIS:
      Careful blood glucose control is essential to prevent long-term complications of
      diabetes. Newer blood glucose meters have a broad variety of features, including
      small size, extended memory capacity, blood glucose manipulation techniques, and
      computer downloading capabilities. The decision to choose a blood glucose meter
      should be based on a number of criteria, including the patient's needs, ease of
      use, and affordability. CONCLUSION: Pharmacists must position themselves to
      differentiate among the numerous blood glucose meters available on the market and
      make appropriate recommendations based on patient-specific needs.

PMID- 9654850
TI  - Analysis of the medical use of marijuana and its societal implications.
AB  - OBJECTIVE: To review the pharmacology, therapeutics, adverse effects, and
      societal implications of the medical use of marijuana. DATA SOURCES: MEDLINE and
      manual searches of English-language marijuana literature, supplemented with
      interviews of scientists currently conducting cannabinoid research. Search terms
      included pain OR palliative care AND cannabis or ALL marijuana; cachexia OR
      appetite OR appetite stimulants; muscle spasticity OR spasm; immune system and
      cannabis; nausea and vomiting and cancer and cannabis. MEDLINE search terms:
      cannabis OR marijuana smoking OR marijuana abuse; all glaucoma; multiple
      sclerosis AND cannabis OR marijuana smoking OR marijuana abuse. STUDY SELECTION:
      Studies on pharmacology, risks, and medical potential of marijuana. DATA
      EXTRACTION: Not applicable. DATA SYNTHESIS: The most prominent effects of
      marijuana are mediated by receptors in the brain. Acute intoxication is
      characterized by euphoria, loss of short-term memory, stimulation of the senses,
      and impaired linear thinking. Depersonalization and panic attacks are adverse
      effects. Increased heart rate and reddened conjunctivae are common physical
      effects. Chronic, high doses may cause subtle impairment of cognitive abilities
      that are appear to be long-term, but of unknown duration. Marijuana may be a risk
      factor for individuals with underlying mental illness. It causes dependence, but
      compared with cocaine, alcohol, heroin, and nicotine, marijuana has little
      addictive power and produces only mild withdrawal symptoms. Marijuana shows
      clinical promise for glaucoma, nausea and vomiting, analgesia, spasticity,
      multiple sclerosis, and AIDS wasting syndrome. CONCLUSION: As a recreational
      drug, marijuana poses dangers, particularly to social and emotional development
      during adolescence and young adulthood. As a medical drug, marijuana should be
      available for patients who do not adequately respond to currently available
      therapies.

PMID- 9654851
TI  - Melatonin and sleep: a balanced view.

PMID- 9654852
TI  - Pharmacoeconomics of biotechnology drugs (2).

PMID- 9654853
TI  - Pharmacists as self-care consultants.

PMID- 9654854
TI  - Immunizations after influenza season: focus on pneumococcal disease.

PMID- 9654855
TI  - Medical information on the Internet: fool's gold or 24 karat?

PMID- 9654856
TI  - Nelfinavir and nevirapine.

PMID- 9654857
TI  - Team approach to HIV exposures.

PMID- 9654858
TI  - Using protocols in the context of pharmacists' patient care responsibilities.

PMID- 9654859
TI  - Creating expectations: a first step toward pharmacist-patient confidentiality.

PMID- 9654860
TI  - New schools strive to carve their own niche in pharmacy education.

PMID- 9654861
TI  - APhA drug treatment protocols: management of gestational diabetes mellitus and
      impaired glucose tolerance during pregnancy. APhA Diabetes Mellitus Panel.

PMID- 9654862
TI  - System for exchanging information among pharmacists in different practice
      environments.
AB  - OBJECTIVES: A system for exchanging patient information among hospital, long-term
      care (LTC), and ambulatory care pharmacies is described, and the influence of
      that system on pharmacist interventions is reported. METHODS: Study sites
      consisted of three ambulatory care pharmacies, one LTC pharmacy, and one hospital
      in a small Midwestern city. Meetings were held by clinicians, the investigators,
      and hospital administrators to plan the information-exchange system. From January
      through June 1996, patients admitted to the hospital were checked to see if they
      came from a participating (source) pharmacy; if so, they were randomly assigned
      to experimental and control groups. The hospital requested preadmission
      information from the source pharmacy for experimental group patients and did not
      do so for control patients. After the information arrived, the hospital
      pharmacists could use it to identify and document drug therapy problems. When an
      experimental group patient was discharged, the hospital sent information to the
      appropriate source pharmacy. A total of 156 patients were enrolled in the study.
      RESULTS: Complete information transfer occurred for 75% of experimental group
      patients. Significantly more experimental group patients than control patients
      had at least one in-hospital pharmacist intervention recorded. Similarly, in the
      ambulatory care pharmacies (but not the LTC pharmacy) significantly more
      interventions per patient were documented for the experimental group. CONCLUSION:
      Hospital and ambulatory care pharmacists documented more interventions for
      patients about whom information had been supplied than for patients for whom that
      information had not been supplied. No difference in intervention rates was
      observed for LTC pharmacists, who were already being supplied information by the
      LTC facilities about patients discharged from the hospital.

PMID- 9654863
TI  - Comparison of targeting a DUR letter intervention at pharmacists separate from
      and in addition to physicians.
AB  - OBJECTIVE: To examine the impact on dipyridamole prescribing of a letter mailed
      to pharmacists and/or physicians. DESIGN: Interrupted time series with control
      series. SETTING: State of Wisconsin. PARTICIPANTS: Physicians and pharmacists
      caring for patients who were prescribed dipyridamole. INTERVENTIONS: The state of
      Wisconsin was divided into four sections, three of which were designated as
      experimental regions (letter to physician only, letter to pharmacist only, and
      letter to both physician and pharmacist) and one of which served as a control
      region. MAIN OUTCOME MEASURES: Cost of drug per patient per month in ambulatory
      and long-term care populations. RESULTS: For 763 long-term care and 586
      ambulatory Medicaid patients, letters sent to both physicians and pharmacists
      resulted in significant reductions in dipyridamole expenditures relative to the
      control group. For long-term care patients, interventions directed at both
      physicians and pharmacists produced significant reductions in dipyridamole
      prescribing relative to interventions directed at physicians alone or pharmacists
      alone. CONCLUSION: Future DUR letter interventions designed to change prescribing
      habits would be more effective if they targeted both physicians and pharmacists,
      particularly in the long-term care setting.

PMID- 9654864
TI  - Michigan Medicaid recipients' perceptions of medication counseling as required by
      OBRA '90.
AB  - OBJECTIVE: To assess pharmacist counseling under OBRA '90 from the Medicaid
      recipient's perspective. Specifically, the study was designed to (1) assess
      pharmacists' compliance with counseling requirements, (2) assess recipients'
      level of satisfaction with the information provided during counseling and whether
      the information provided increased their comfort level in taking medication
      correctly, and (3) determine relationships between variables associated with
      pharmacist counseling and recipient satisfaction and comfort level. DESIGN: Cross
      sectional telephone survey of Medicaid recipients. Medicaid recipient or
      caregiver was the unit of measure. SETTING: Michigan. PATIENTS: 408 recipients
      who received new prescriptions during a one-week period in November 1995.
      INTERVENTIONS: Telephone survey. MAIN OUTCOME MEASURE: Recipients' perception of
      whether an offer to counsel was made. RESULTS: Only 104 (25.5%) recipients
      indicated that someone offered counseling for their new prescription, and only 62
      (15.2%) recipients indicated they knew of the requirement; 163 (40.0%) indicated
      someone offered counseled them. Counseled recipients were satisfied with the
      amount, quality, and way the information was presented, and were more likely to
      assign a higher level of importance to pharmacist counseling. The majority of
      respondents indicated high levels of comfort in using their medications safely,
      with those who were counseled expressing a higher level of comfort. CONCLUSION:
      From the perspective of the Medicaid recipient, pharmacies are failing to offer
      counseling for most new prescriptions. The results indicate that counseling
      improves measures of recipient comfort in using medications safely and enhances
      the level of importance patients assign to pharmacist counseling.

PMID- 9654865
TI  - Smoking cessation: Part 2--Pharmacologic approaches.
AB  - OBJECTIVE: To present the concept of nicotine-replacement therapy (NRT) and the
      pharmacologic approaches, nonprescription and prescription, to smoking cessation.
      DATA SOURCES: Current clinical literature. DATA SYNTHESIS: NRT can be delivered
      through a number of different nicotine-containing dosage forms (e.g., gum, patch,
      nasal spray, oral inhaler). The Agency for Health Care Policy and Research
      (AHCPR) recommends using the nicotine patches for routine clinical practice and
      the American Psychiatric Association (APA) recommends the use of the patches and
      gum as initial pharmacotherapies for smoking cessation. There are no comparative
      studies indicating the superiority of one form or another at relieving nicotine
      withdrawal symptoms. Of the other pharmacologic agents used for smoking
      cessation, bupropion hydrochloride demonstrates the most promise. CONCLUSION: The
      pharmacist can assist the consumer with the selection of an OTC smoking cessation
      product and serve as an informational resource to consumers and physicians
      desiring information on prescription drug products for smoking cessation.

PMID- 9654867
TI  - Gestational diabetes.
AB  - OBJECTIVE: To review the detection, diagnosis, and clinical management of
      gestational diabetes. DATA SOURCES: MEDLINE, Gestational Diabetes Guideline
      Review, 1968-1998. STUDY SELECTION: By the author. DATA EXTRACTION: By the
      author. DATA SYNTHESIS: Gestational diabetes is a common complication of
      pregnancy, occurring in 2% to 6% of pregnancies. Uncontrolled gestational
      diabetes is associated with increased infant morbidity and mortality, macrosomia,
      and cesarean deliveries, and is a strong marker for the future development of
      maternal diabetes mellitus. Women with risk factors for gestational diabetes
      should be screened for glucose intolerance at 24 to 28 weeks' gestation. If a
      screening plasma glucose concentration is 140 mg/dL or greater one hour after a
      50 gram oral glucose load, then a diagnostic 100 gram, three-hour oral glucose
      tolerance test should be performed. Medical nutrition therapy is the cornerstone
      of management and must be designed to meet individual needs. Self-monitoring of
      blood glucose should be taught to and performed by all women with gestational
      diabetes. Insulin, which does not readily cross the placental barrier, is the
      drug therapy of choice in women failing medical nutrition therapy. CONCLUSION:
      Pharmacists can optimize overall care by educating, monitoring, and intervening
      or assisting the patient in the management of gestational diabetes.

PMID- 9654866
TI  - The role of pharmacy in the management of patients with temporomandibular
      disorders and orofacial pain.
AB  - OBJECTIVE: To provide information regarding the current understanding of the
      etiology and treatment, both nonpharmacologic and pharmacologic, of orofacial
      pain conditions including temporomandibular disorders (TMDs). This review briefly
      discusses the etiology and pathophysiology underlying the development of TMDs,
      generally accepted nonpharmacologic methods of treatment, and the most common
      current pharmacologic management approaches. DATA SOURCES: Current medical
      literature and the authors' clinical experiences. DATA SYNTHESIS: TMDs encompass
      a number of diagnostic subgroups that involve the masticatory musculature, the
      temporomandibular joint(s), and associated structures. More than 10 million
      individuals in the United States are affected by TMDs. Most current pharmacologic
      management approaches in the treatment of orofacial pain conditions, including
      TMDs, involve the use of antidepressants, anticonvulsants, muscle relaxants,
      corticosteroids, and nonsteroidal anti-inflammatory drugs. CONCLUSION: Inclusion
      of pharmacists who are knowledgeable in the nonpharmacologic and pharmacologic
      treatment approaches on the TMD management team would improve therapeutic
      monitoring, follow-up, and outcomes in these patients.

PMID- 9654868
TI  - Pharmacist-patient privilege, confidentiality, and legally-mandated counseling: a
      legal review.
AB  - OBJECTIVE: To indicate the necessity for uniform, privileged status of pharmacist
      patient communications. DATA SOURCES: Published cases (LEXIS), literature (NEXIS
      and MEDLINE), and abstracts available through November 1997. CASE SELECTION AND
      DATA ABSTRACTION: Selected by the authors for inclusion based on objectives,
      publication in English, and usefulness of information for practicing pharmacists.
      DATA SYNTHESIS: Since pharmacists are now legally required to counsel patients
      under federal and state laws, protection of the confidentiality of such
      information is of concern. Statutes are largely silent on the issue of pharmacist
      patient communications, particularly oral communications. Some states recognize
      privilege (protection from subpoenas and court orders), others provide
      confidentiality only (information must be divulged only upon subpoena or court
      order), and most states specify neither type of protection for pharmacist-patient
      communications. An evaluation of case law indicates personal and legal risks, for
      both pharmacist and patient, associated with unprivileged communications
      occurring within a counseling situation. CONCLUSION: Pharmacist-patient
      communications must be granted privileged status, in all states, to protect both
      pharmacist and patient if pharmacists are to fulfill their legally-mandated
      counseling responsibilities.

PMID- 9654869
TI  - New therapeutic monoclonal antibodies target kidney transplant rejection and
      cancer.

PMID- 9654870
TI  - Susceptible to tetanus and diphtheria? Immunize against both.

PMID- 9654871
TI  - On-line learning: trends in continuing education.

PMID- 9654872
TI  - A collective review of the world literature on hepatic cryotherapy.
AB  - Published results of hepatic cryotherapy are now available for almost 900
      patients. Its safety is well established and its clinical role in treating
      patients with unresectable hepatoma or liver metastases from colorectal carcinoma
      is well supported by tumour marker and survival data; the results in the
      treatment of neuroendocrine liver metastases are promising. Its role as an
      alternative to liver resection is not yet well supported by long-term data.
      Although different adjuvant treatment protocols have been used following the
      cryotherapy of colorectal liver metastases, the effect of adjuvant treatment on
      recurrence or survival has not been assessed in prospective studies. Laparoscopic
      hepatic cryotherapy is feasible in selected patients with suitable tumour
      locations. However, the proportion of patients who might be usefully treated with
      this technique is not yet well established. The mechanisms of tissue destruction
      by freezing are reviewed.

PMID- 9654873
TI  - Thrombogenicity of heparin and non-heparin bound arterial prostheses: an in vitro
      evaluation.
AB  - The effect on graft thrombogenicity of binding heparin to the luminal surface of
      prosthetic arterial grafts was investigated. Venous blood was obtained from
      healthy volunteers and exposed for 30 minutes to tubular segments of standard
      knitted dacron, polytetrafluoroethylene (PTFE) and a recently introduced heparin
      bound knitted dacron graft. After this exposure the fibrinogen level of each
      sample was measured. The median (range) fibrinogen levels (expressed as a
      percentage of that in unexposed blood samples) were: standard dacron 3.5% (0
      5.4%); PTFE 95.5% (0-121.1%); and heparin-bound dacron 79.8% (3.8-109.6%).
      Fibrinogen levels in the standard dacron group were significantly less than that
      of the PTFE and heparin-bound dacron groups (P < 0.05). No significant difference
      was found between the fibrinogen levels of the PTFE and heparin-bound dacron
      groups (P = 0.35). These findings suggest that heparin binding significantly
      reduces fibrinogen consumption and hence may reduce graft thrombogenicity.

PMID- 9654874
TI  - Effectiveness of topical non-steroidal anti-inflammatory drugs in the management
      of breast pain.
AB  - A prospective study of the effectiveness of the topical application of non
      steroidal anti-inflammatory drugs (NSAIDs) as a gel preparation was carried out
      in 26 women with severe breast pain. The results showed a satisfactory relief of
      pain in 81% of the women: 11 of 13 with cyclical pain, eight of 11 with non
      cyclical pain, and in two women with severe scar pain after lumpectomy and
      radiotherapy. Topical NSAID gel was applied as required; the relief of severe
      pain was rapid and no side effects were reported. These factors compare
      favourably with established recommended treatments which usually involve months
      of continuous treatment, tailoring of drug dosages and a significant incidence of
      intolerable side effects. This study has shown that topical NSAID application is
      an effective, safe, acceptable and easily administered treatment for severe
      cyclical and non-cyclical breast pain.

PMID- 9654875
TI  - Surgical lessons learned from the Shigella dysenteriae type I epidemic.
AB  - An epidemic of Shigella dysenteriae type I is spreading through Africa. It is a
      particularly infectious and virulent form of dysentery which can cause clinical
      confusion with other endemic diseases and may present to the surgeon as a result
      of its complications. A total of 140 children with Shigella dysenteriae type I
      presented to the paediatricians at King Edward VIII Hospital in 1995; 35 were
      referred to the surgeons because of abdominal tenderness, distension, peritonitis
      or perforation. Ten children underwent laparotomy--four for peritonitis and six
      for perforation. Of the four children with peritonitis, three had transmural
      colitis. Therefore laparotomy was only performed for objective evidence of
      perforation. Of the subsequent non-operated group with the clinical features of
      peritonitis, none developed further surgical problems in the acute phase and none
      died. It is suggested that surgery in the acute phase should be avoided unless
      there is evidence of perforation.

PMID- 9654876
TI  - Serum albumin: a prognostic indicator in patients with colorectal cancer.
AB  - Various prognostic factors for survival have been identified in patients with
      colorectal cancer. However, although it has been suggested that the pre-treatment
      serum albumin concentration is a prognostic indicator in certain malignant
      diseases (melanoma, prostate cancer, leukaemia), its value in patients with
      colorectal cancer remains unclear. This study investigated the prognostic value
      of serum albumin in this patient group. A total of 431 patients presenting to the
      Professorial Surgical Unit between 1972 and 1985 were analysed in this study.
      Using the Cox proportional hazard model, age, tumour stage (Dukes' stage) and
      tumour differentiation were shown to be independent prognostic factors for
      survival in patients with localized colorectal cancer. In addition, the pre
      treatment serum albumin concentration was found to be an independent prognostic
      indicator. This is the first such documentation for patients with 'curable'
      colorectal cancer.

PMID- 9654877
TI  - Total gastrectomy for gastric cancer: the rationale for J-pouch reservoir.
AB  - This prospective study examines the results of total gastrectomy in 56
      consecutive patients (38 males and 18 females) and compares Hunt-Limo-Basto J
      pouch reconstruction (23 patients) with simple oesophago-jejunostomy (33
      patients). There was no difference in morbidity and mortality between the two
      groups, which are fairly well-matched proportionately in age, concomitant disease
      and stage of disease. There was, however, a male predominance in the non-pouch
      group. Anastomotic leak occurred in only one patient with gastric reconstruction
      while one duodenal stump leak developed in the non-pouch patient. Construction of
      the stapled J-pouch extended the operation by a mean time of 14 min. The only
      advantage of the J-pouch is that it facilitates introduction of a larger diameter
      stapler for oesophago-jejunostomy. The nutritional benefit remains uncertain.

PMID- 9654878
TI  - Wounds of Wewak, Papua New Guinea.
AB  - Wounds encountered in the outpatients (A&E) department of Wewak General Hospital
      in Papua New Guinea were observed during a 3-week visit. A series of 14
      accidental wounds and nine resulting from attack were analysed. It was found that
      there were predisposing social factors of alcohol, conjugal disputes and
      'payback' retribution attacks. Physical factors affecting the outcome were
      nutritional status and a high rate of wound infection. Broken bottles and cans
      caused some of the injuries. Many aspects of the problem were thus the same as in
      the UK, but the resources available to help the patients were much more limited.

PMID- 9654879
TI  - Pre-admission clinic in an orthopaedic department: evaluation over a 6-month
      period.
AB  - A pre-admission clinic for patients undergoing elective orthopaedic surgery has
      been used at the Royal Surrey County Hospital, Guildford, for the past 3 years.
      This report audits the activities of the clinic over a period of 6 months. Data
      regarding the patients who were invited to the pre-admission clinic during the
      study period were analysed. In all, 232 patients were asked to attend the clinic
      and a total of 221 (95.2%) attended. Of these patients, 10 had their operations
      cancelled and three had their operations postponed in the clinic due to various
      medical and social reasons. Another 28 operations were cancelled or postponed at
      a later stage. All of the postponed procedures were eventually performed within 3
      months. Of the 232 patients, 180 (77.5%) underwent their operation on the
      arranged day without any complications. The pre-admission clinic in our
      orthopaedic department helps us to prevent a significant number of operation
      cancellations on the day of admission. It also facilitates an extensive pre
      operative assessment of the patients and reduces the ward-based workload of the
      junior medical staff. More extensive use of the pre-admission clinic is
      recommended.

PMID- 9654880
TI  - Prospective study on factors delaying surgery in ruptured abdominal aortic
      aneurysms.
AB  - Delays between rupture, eventual diagnosis and the repair of abdominal aortic
      aneurysms (AAAs) can significantly affect outcome, but the reasons for such
      delays in management are not always clear. A prospective study was, therefore,
      performed on 30 patients with ruptured AAAs. Twenty-three male and seven female
      patients, mean age 71.3 years, were studied. The general practitioner had made
      the correct diagnosis in only 38% of cases and the most common misdiagnosis was
      renal colic (24%). Non-vascular hospital doctors made the correct diagnosis in
      55% of cases, but patients with back pain were the most frequently misdiagnosed
      by both types of doctor. The performance of an ultrasound scan significantly
      delayed referral to the vascular unit from a median of 0.75 to 2.50 hours and was
      of little benefit in aiding the diagnosis. In conclusion, the most striking delay
      factors in the management of ruptured AAAs are the high incidence of misdiagnosis
      and the lack of benefit of ultrasound scanning.

PMID- 9654881
TI  - Trigeminal neuralgia, trophic ulceration and the plastic surgeon.
AB  - An 80-year-old woman presented with ulceration to the right alar margin about 20
      years after first undergoing treatment for trigeminal neuralgia. This was
      reconstructed with a sensory innervated left nasal flap. Two years later she
      required an innervated left forehead flap to correct a secondary ectropion of the
      right lower eyelid, and the following year required further surgery to repair a
      defect on her chin. Cosmesis remains satisfactory with no further ulceration 2
      years after the last operation.

PMID- 9654882
TI  - What do plastic surgeons do?
AB  - The image of plastic surgery as portrayed by the media is of concern to all
      plastic surgeons. In order to assess knowledge about the specialty, a
      questionnaire was devised and given to five groups of participants: general
      practitioners, medical students, nurses, plastic surgical out-patient attendees,
      and the general public. The results revealed that general practitioners, nurses
      and medical students in the Cambridge area are, on the whole, knowledgeable about
      the role of plastic surgery. However, the general public are not so well educated
      and 23.7% of them could not think of five conditions treated by plastic surgeons,
      and felt that burns and cosmetic problems were the commonest conditions dealt
      with. Improved liaison with general practitioners, other specialties and more
      teaching of undergraduates, coupled with more effective promotion of the skills
      on offer might permit better use to be made of the specialty.

PMID- 9654883
TI  - A comparison of conservative, radical and laser palatal surgery for snoring.
AB  - Reports of snoring are common among serviceman in the armed forces. Continuous
      positive airway pressure (CPAP) is usually an inappropriate modality for
      servicemen, but surgery, although requested, is very painful. In an attempt to
      reduce the pain, a laser has been used to perform uvulopalatopharyngoplasty and
      the more conservative uvulopalatoplasty has also been performed. Before
      proceeding to a randomized trial, this retrospective study was performed by
      questionnaire comparing these operations with conventional
      uvulopalatopharyngoplasty. Fifty-two completed replies from 63 patients were
      analysed. The results have to be interpreted with caution because of the small
      sample sizes; however, the results in the three groups were similar. The study
      suggests that each operation works well, but that any reduction in pain from
      performing uvulopalatoplasty or by using a laser is likely to be small. The study
      also found that the incidence of dryness as a complication is much higher than
      previously estimated.

PMID- 9654884
TI  - An unnecessary femoral amputation?
AB  - Non-traumatic gas gangrene is extremely rare. It is commonly associated with
      perforation of an occult gastro-intestinal cancer. The patient's course is
      usually fulminant. We report a case of subcutaneous emphysema and myonecrosis of
      the lower extremity due to a perforated carcinoma of the large bowel. The
      diagnosis of colonic cancer was suspected but treatment was regrettably delayed
      leading to the perforation and subsequent lower extremity gas gangrene. The
      patient survived following a femoral amputation.

PMID- 9654885
TI  - Candidal urinary tract infection as a cause of pneumaturia.
AB  - Colonization of the urinary tract by Candida species occurs particularly in
      diabetic or immunocompromised patients. We report the cases of two patients
      presenting with pneumaturia and urinary tract infection who were initially
      thought to have colovesical fistulae. In both patients a diagnosis of
      emphysematous pyelonephritis or cystitis due to candidal infection was
      subsequently made. These cases serve as a reminder of this rare presentation of a
      not uncommon urinary tract infection.

PMID- 9654886
TI  - Splenosis of the mesoappendix: case report and review of the literature.
AB  - The development of splenosis is a known consequence of splenic rupture. A case is
      presented of acute appendicitis in a patient with a past history of abdominal
      trauma who required laparotomy for unknown reasons. During appendicectomy a mass
      was found in the mesoappendix which proved to be evidence of splenosis.

PMID- 9654887
TI  - Small bowel obstruction caused by a dislodged biliary stent.
AB  - Biliary stents are commonly used in the management of obstructive jaundice.
      Complications at the time of insertion are not uncommon, but late complications
      due to dislodged stents have not been previously reported.

PMID- 9654888
TI  - Myxoglobulosis, a rare variant of appendiceal mucocele, occurring secondary to an
      occlusive membrane.
AB  - A 77-year-old man presented with altered bowel habit and episodic right lower
      abdominal discomfort. A barium enema showed a large smooth filling defect in the
      caecum and at operation his appendix was seen to be hugely distended.
      Pathological examination showed myxoglobulosis, a rare variant of mucocele of the
      appendix. The appendiceal orifice was completely occluded by an imperforate
      membrane with no communication between the appendix and caecum. This is the first
      published report in the English language of appendiceal myxoglobulosis in
      association with such an occlusive membrane.

PMID- 9654889
TI  - Extracranial giant cell arteritis.
AB  - Although giant cell arteritis (GCA) of the extracranial arteries is said to be
      relatively frequent, clinical manifestations are rarely recognized. We describe a
      case presenting with intestinal perforation who subsequently died with active GCA
      of the coronary, mesenteric and temporal vessels.

PMID- 9654890
TI  - A mathematical model of growth of population of fish in the larval stage: density
      dependence effects.
AB  - A mathematical model for the growth of a population of fish in the larval stage
      is proposed. The emphasis is put on the first part of the larval stage, when the
      larvae are still passive. It is assumed that during this stage, the larvae move
      with the phytoplankton on which they feed and share their food equally, leading
      to ratio-dependence. The other stages of the life cycle are modeled using simple
      demographic mechanisms. A distinguishing feature of the model is that the exit
      from the early larval stage as well as from the active one is determined in terms
      of a threshold to be reached by the larvae. Simplifying the model further on, the
      whole dynamics is reduced to a two dimensional system of state-dependent delay
      equations. The model is put in perspective with some of the main hypotheses
      proposed in the literature as an explanation to the massive destruction which
      occurs between the egg stage and the adult stage.

PMID- 9654892
TI  - Food chain dynamics in the chemostat.
AB  - The asymptotic behavior of a tri-trophic food chain model in the chemostat is
      studied. The Monod-Herbert growth model is used for all trophic levels. The
      analysis is carried out numerically, by finding both local and global
      bifurcations of equilibria and of limit cycles with respect to two chemostat
      control parameters: the dilution rate of the chemostat and the concentration of
      input substrate. It is shown that the bifurcation structure of the food chain
      model has much in common with the bifurcation structure of a one-dimensional map
      with two turning points. This map is used to explain how attractors are created
      and destroyed under variation of the bifurcation parameters. It is shown that low
      as well as high concentration of input substrate can lead to extinction of the
      highest trophic level.

PMID- 9654891
TI  - A modified model for projecting age-structured populations in random
      environments.
AB  - A discrete-time age-structured population model with vital rates linked to a
      stochastic environmental process was developed as a generalization of an existing
      model by making the explicit link between variability in the vital rates and
      variability in the environment more flexible. This modified model uses
      biologically relevant probability distributions for the vital rates, and allows
      for temporal autocorrelation and an arbitrary covariance structure between vital
      rates. Through simulations, the properties of the projected population in the
      short-term were investigated and compared to analytical approximations. The
      distribution of the total population size did not quickly approach lognormality
      under all conditions. Furthermore, the sensitivity of the vital rates to the
      environmental process had a strong effect on the variance and distribution of the
      projected population size. These results suggest that short-term projections need
      to be carried out through simulation methods, as the analytical approximations
      technically apply only to the long-run asymptotic behavior. Techniques for
      parameter estimation were considered; recommendations depend on the form of the
      data available. The approach described allows the empirical calculation of the
      probability distribution for predicted population size, a quantity relevant to
      the use of formal decision analysis in natural resource management.

PMID- 9654893
TI  - A model of multiple tumorigenesis allowing for cell death: quantitative insight
      into biological effects of urethane.
AB  - This paper considers the utility of a stochastic model of carcinogenesis proposed
      by Yakovlev and Polig [Math. Biosci. 132 (1996) 1-33] in the analysis of
      experimental data on multiple tumors induced by chemical carcinogens. The model
      provides a good description of published data on multiple tumors developing in
      the lungs of mice in response to different schedules of urethane. The
      distribution of pulmonary tumor counts appears to be negative binomial for each
      period of time after exposure to urethane. Our results suggest that the rate of
      administration of urethane has little effect both on the mean number of initiated
      cells per unit dose and on the rate of formation of lesions responsible for cell
      death. As our estimates show, more than 80% of initiated cells die in the course
      of tumor promotion. The model is robust to variations in the rate of urethane
      excretion given a fixed total dose of the carcinogen. Some prospects for further
      development of the model to allow for expansion of promoted cell clones are
      discussed.

PMID- 9654894
TI  - Statistical certification of eradication of poliomyelitis in the Americas.
AB  - The last confirmed case of paralytic poliomyelitis due to indigenous wild
      poliovirus in the Americas occurred in Peru in 1991. In 1994 the International
      Commission on Polio Eradication of the Pan American Health Organization (PAHO)
      deemed eradication of polio from the area to have occurred, based on its
      strategic efforts and the observed results. A mathematical model is presented
      here which relates the time elapsed since that last detected case of paralytic
      poliomyelitis caused by wild poliovirus to the probability that the transmission
      of indigenous wild poliovirus has been stopped. The appropriateness of applying
      the model to various geographical areas of the Americas is investigated using
      data about the occurrence of confirmed cases of polio since 1984, the time of the
      eradication initiative adopted by PAHO. The model suggests that if four year have
      elapsed since the last reported confirmed case of polio caused by wild
      poliovirus, and no other confirmed cases have been identified, the probability of
      undetected indigenous wild poliovirus transmission is less than 5%. An important
      assumption is that the eradication strategy implemented by PAHO has yielded
      steady improvements. A consequence of this approach is that the annual
      probabilities of persistence given by the model are conservative, in the sense of
      being higher than the true, but unknown a priori probabilities, and more so with
      each passing year. It is thus seen that the model results are compatible with the
      conclusion reached by PAHO in 1994. The model takes into account the intensity of
      surveillance of each country in the region, measured by the corresponding rates
      of acute flaccid paralysis (AFP). Because importations of wild poliovirus may
      occur from other regions of the world, surveillance efforts are being maintained
      in the Americas until global eradication has been achieved.

PMID- 9654895
TI  - A plague upon your cattle.

PMID- 9654896
TI  - Ischemic stroke syndromes: classification, pathophysiology and clinical features.

PMID- 9654897
TI  - The role of correctional facilities in public health: the example of sexually
      transmitted diseases.

PMID- 9654898
TI  - The economic cost of strict syringe control.

PMID- 9654899
TI  - The need for compassionate care: HIV infection among incarcerated women.

PMID- 9654900
TI  - The creative clinician: images in medicine.

PMID- 9654901
TI  - Health care quality improvements in Rhode Island diabetes mellitus.

PMID- 9654902
TI  - AIDS morbidity and mortality in Rhode Island.

PMID- 9654903
TI  - Cancer control report card: Rhode Island, 1998.

PMID- 9654904
TI  - Queen Elizabeth I's bout with smallpox.

PMID- 9654905
TI  - [Dr. Alport and London].

PMID- 9654906
TI  - [Effects of doxazosin and hydralazine on insulin sensitivity and sympathetic
      function in spontaneously hypertensive rat (SHR)].
AB  - Since insulin resistance and/or hyperinsulinemia may contribute to structural
      changes of the vascular wall, the influence of antihypertensive agents on insulin
      sensitivity could interfere with the long term outcome of blood pressure
      reduction. Although it is postulated that increased peripheral circulation due to
      vasodilating agents improves insulin sensitivity, reflex sympathetic activation
      elicited by blood pressure reduction may influence insulin sensitivity. Thus we
      investigated the different effects of an alpha blocker (doxazosin) as well as a
      direct vasodilation (hydralazine) on insulin sensitivity and on sympathetic
      function in spontaneously hypertensive rats (SHR). Doxazosin and hydralazine
      decreased mean arterial pressure to a similar extent. Doxazosin, but not
      hydralazine decreased steady state blood glucose. Plasma norepinephrine increased
      in doxazosin and hydralazine treated groups as compared to the control group.
      Thus, despite their similar effects on blood pressure and plasma norepinephrine,
      alpha-1 blocker improved insulin sensitivity while the direct vasodilator failed
      to do so, and this difference is probably related to blockade of the alpha-1
      receptor rather than to peripheral vasodilation.

PMID- 9654907
TI  - [Effects of glucose and TGF-beta 1 on the proliferation of cultured human
      peritoneal mesothelial cells].
AB  - The exfoliation and decrease is peritoneal mesothelial cells and the presence of
      interstitium hyperplasia are often observed in peritoneal membrane dysfunction
      caused by long-term peritoneal dialysis. The suppression of peritoneal
      mesothelial cell proliferation may be the cause of these phenomena. The objective
      of this study is to clarify the mechanism by which highly concentrated glucose of
      peritoneal dialysis fluid inhibits mesothelial cell proliferation. We examined
      the effect of highly concentrated glucose in the medium on human peritoneal
      mesothelial cell proliferation and TGF-beta 1 mRNA expression. The effect of
      Ham's F12 media containing various levels of glucose concentration was compared
      with that of normal medium. We investigated human peritoneal mesothelial cell
      proliferation by [3H] thymidine incorporation assay and TGF-beta 1 mRNA
      expression on human mesothelial cells by the RT-PCR method. The suppression
      effect of glucose and TGF-beta 1 on human peritoneal mesothelial cell
      proliferation was dose-dependent (glucose; 0-5%, TGF-beta 1; 0-1000 pg/ml). TGF
      beta 1 mRNA of cells in 4% glucose medium was greater than that in the control
      medium. The glucose-induced suppression of human peritoneal mesothelial cell
      proliferation was relieved by LAP and TGF-beta neutralizing antibody. In
      conclusion, TGF-beta 1 may play a critical role in inhibiting mesothelial cell
      proliferation in media with highly concentrated glucose.

PMID- 9654908
TI  - [The impact of low calcium dialysate (1.25 mmol/l; LCD) on bone metabolism in
      CAPD patients].
AB  - The aim of this study was to evaluate the influence of LCD on bone metabolism,
      and assess the indication of LCD. Fourteen patients on CAPD (m = 8, f = 6) were
      converted to LCD following over 1 year on standard calcium dialysate (1.75
      mmol/l; SCD) treatment, and followed for 1 year. The biochemical measurements
      included plasma levels of Ca, P, ALP, and i-PTH. The bone mineral density (BMD)
      was evaluated using dual energy x-ray absorptiometry. Ca-carbonate and calcitriol
      were administered to maintain plasma Ca levels within the normal range. The
      patients were divided into three groups on the basis of the i-PTH levels just
      before the conversion to LCD. Group 1; n = 5, i-PTH < 65. Group 2; n = 5, 65 < or
      = i-PTH < 200. Group 3; n = 4, 200 < or = i-PTH (pg/ml). Mean BMD Z scores
      decreased significantly in group 3. Mean serum i-PTH significantly increased in
      all groups. These results suggest that LCD is effective for treating adynamic
      bone disease, which is seen in high frequency in patients undergoing peritoneal
      dialysis. However, these results also pointed to the disadvantage of worsening
      the secondary hyperparathyroidism. In conclusion, LCD should be used carefully in
      patients whose i-PTH levels are high, because of the possibility of bone mineral
      loss.

PMID- 9654909
TI  - [The influence of correction of acidosis on plasma level of branched-chain amino
      acids in chronic hemodialysis patients].
AB  - Seven patients undergoing chronic hemodialysis three times a week and whose
      plasma bicarbonate concentration on predialysis was consistently under 18 mmol/l
      due to bicarbonate dialysis (BCD), were treated with BCD for 2 weeks, then
      switched to acetate-free biofiltration (AFB) for 8 weeks. In both periods, the
      same high flux dialyzer (AN69HF) was used. The treatment time, dialysate flow
      rate and blood flow rate were kept constant in each patient during both periods.
      Plasma bicarbonate concentration (HCO3-), serum urea nitrogen (SUN), serum
      creatinine (Cr) and plasma amino acids concentrations (AA) were measured before
      dialysis and KT/V was calculated on the 2nd days of the last week in both
      periods. HCO3- on AFB was significantly higher than that on BCD (16.4 +/- 0.9 vs
      19.9 +/- 1.8 mmol/l; p < 0.05). SUN on AFB was significantly lower than that on
      BCD even though the dialysis schedule and dietary content were not changed (84.7
      +/- 3.7 vs 76.6 +/- 3.8 mg/dl; p < 0.05). TP, Cr and KT/V were not significantly
      different. Plasma total amino acid concentration (TAA) and plasma essential amino
      acid concentration (EAA) were not significantly different in both periods. In
      contrast, plasma branched-chain amino acid concentrations (BCAA) on AFB were
      significantly higher than that on BCD (313.5 +/- 44.3 vs 390.3 +/- 50.7 mumol/l;
      p < 0.05). Plasma BCAA concentrations, valine (VAL), leucine (LEU) and isoleucine
      (ILE), were significantly higher on AFB than that on BCD, respectively (p <
      0.05). These findings suggest that optimal correction of the metabolic acidosis
      in chronic hemodialysis patients by AFB leads to a significant increase in plasma
      BCAA concentration.

PMID- 9654910
TI  - [An electron microscopic study of circumferential mesangial interposition in
      various renal diseases].
AB  - It has been reported that circumferential mesangial interposition (CMI) is an
      important morphological feature suggesting the progression of glomerulosclerosis
      in glomerular disease. The relation between CMI and its associated lesions was
      investigated in various renal diseases by electron microscopy. In 276 patients,
      of whom the glomeruli were observed by electron microscopy, CMI was observed non
      specifically in 48 patients with various glomerular diseases (IgA nephropathy,
      11; non-IgA glomerulonephritis, 1; membranoproliferative glomerulonephritis, 8;
      membranous nephropathy, 5; lupus glomerulonephritis, 12; toxemia of pregnancy, 2;
      diabetic nephropathy, 7; mitomycin nephropathy, 1; and Seckel's dwarfism
      patients, 1). The glomeruli with CMI showed a marked increase in mesangial
      matrix, as well as various grades of mesangial cell proliferation. Mesangiolysis
      associated with subendothelial widening was observed in a lesion of CMI in most
      cases. This phenomenon appears to be an initial alteration that conducts
      proliferated cells to the peripheral portion of a capillary loop. Localized
      severe thinning of the glomerular basement membrane was frequently combined with
      CMI, particularly in IgA nephropathy patients. Endothelial cells were
      occasionally interposed into the widened subendothelial space. Subendothelial
      deposits were noticed in the CMI lesion, particularly in MPGN patients. In
      conclusion, in the process of glomerulosclerosis progression in various
      glomerular diseases, lytic and edematous changes initially occur in the mesangio
      subendothelial system (mesangiolysis and subendothelial widening), then
      proliferating mesangial cells extend into the widened space (between GBM and
      endothelial cells), and reach the peripheral portion of a capillary loop.

PMID- 9654911
TI  - [Participation of apoptosis in renal amyloidosis].
AB  - Renal amyloidosis shows symptoms of renal dysfunction due to the deposition of
      amyloid protein in the kidney. Recently, it was reported that apoptosis plays an
      important role in the pathogenesis of type-2 diabetes mellitus and Alzheimer's
      disease of which amyloid deposition is seen in the tissue. We investigated
      whether or not apoptosis and related factors are observed in renal amyloidosis.
      In situ nick end labeling (TUNEL) was performed in seven autopsied renal tissues
      with primary and secondary amyloidosis and 10 autopsied renal tissues without
      renal disease as the control. The number of TUNEL-positive cells was
      significantly increased in both the glomeruli and tubulus of the kidney with
      amyloidosis than in the control. Electron microscopic analysis was performed on
      one biopsied renal tissue with amyloidosis and six biopsied renal tissues with
      minor abnormalities as the control. Typical apoptotic cells were observed only in
      the former. Bax product, an inducer of apoptosis, and Bcl-2 protein, an inhibitor
      of apoptosis, were examined immunohistochemically in the seven autopsied renal
      tissues with amyloidosis and 10 autopsied control tissues. Bax was overexpressed
      in the tubulus and glomeruli of subjects with renal amyloidosis, compared to the
      normal controls. However, Bcl-2 protein was not detected in the glomeruli in any
      of the subjects examined. These results indicate that apoptotic cells are
      increased in number in renal amyloidosis and Bax overexpression may play an
      important role in this increase.

PMID- 9654912
TI  - [A case of systemic AA amyloidosis complicating Crohn's disease].
AB  - Although systemic AA amyloidosis complicating Crohn's disease has been found in
      0.5 to 6% in America and Europe, it is relatively rare in Japan. We report a case
      of systemic AA amyloidosis complicating Crohn's disease. In 1979, a 26-year-old
      Japanese man presented with diarrhea, melena and perianal abscesses, and was
      diagnosed as having Crohn's disease. He was treated with oral prednisolone,
      salazosulfapyridine and diet therapy. However, the gastrointestinal symptoms
      recurred and he was hospitalized several times. In 1991, his thyroid gland was
      found to be swollen, but with normal thyroid function, and his thyroid gland
      became larger subsequently. In October 1995, he showed renal dysfunction (blood
      urea nitrogen 33.2 mg/dl; serum creatinine 1.5 mg/dl) with proteinuria. His renal
      function had been deteriorating rapidly. On September 13, 1996, he was admitted
      to the Tsukuba University Hospital. At the time of admission, his renal function
      showed a blood urea nitrogen of 129.5 mg/dl with a creatinine of 5.4 mg/dl. The
      urine contained 0.8 g of protein per 24 hours. He presented with diarrhea for
      several days before admission and was treated with central venous
      hyperalimentation. Despite supportive care, he developed end-stage renal failure,
      then hemodialysis was initiated on October 7. His condition was complicated by a
      complete auriculoventricular block on October 18. He died of hemoperitoneum on
      October 25. On postmortem examination, extensive amyloid deposits were found in
      multiple organs including kidneys, intestine, heart, thyroid gland, lungs, liver,
      spleen, pancreas, gall bladder, adrenal glands, testis, prostate, bone marrow and
      parathyroid glands. Analysis of amyloid protein in the autopsy specimens showed
      type AA.

PMID- 9654913
TI  - [A case of hepatitis C virus associated membranous glomerulonephritis ameliorated
      by corticosteroid therapy].
AB  - We report a 50-year-old male patient with hepatitis C virus (HCV)-associated
      membranous glomerulonephritis (MN), for which he had been treated with
      corticosteroid therapy for one and a half years. This patient received blood
      infusion at 38 years of age. He visited our hospital because of liver dysfunction
      at 42 years. One year later, proteinuria and microhematuria were pointed out (43
      years). Renal biopsy revealed MN with focal fibrocellular crescents. HBsAg,
      cryoglobulin, rheumatoid factor were all negative. Prednisolone was administered
      at the dose of 30 mg/day for 4 weeks and tapered subsequently. The steroid
      treatment was effective (urinary protein excretion: 4.2-->0.3 g/day, serum
      albumin: 2.4-->4.0 g/dl, 3 months later), and transaminase slightly elevated (GPT
      50-->60-80 IU/l). One and a half years later he proved to be positive for HCV
      antibody, and corticosteroid administration was terminated. Subsequently
      proteinuria increased, and reached 3.0 g/day 6 years later. However, serological
      markers and ultrasonographic study for chronic hepatitis revealed mild changes of
      the liver. These findings suggest that corticosteroid therapy is not
      contraindicated against HCV-associated MN, and may possibly be used as the
      treatment for this condition.

PMID- 9654914
TI  - [A case of scleroderma renal crisis with massive pericardial effusion and
      positivity on antiphospholipid antibody test].
AB  - A 47-year-old woman was admitted to our hospital for evaluation of general
      fatigue and dyspnea. She had been diagnosed with progressive systemic sclerosis
      (PSS) when she was 39 years of age, on the basis of Raynaud's phenomenon,
      proximal sclerosis, and pigmentation of the skin. On admission, her blood
      pressure was 206/128 mmHg. Funduscopy revealed grade III (Keith & Wagener)
      hypertensive retinopathy. Laboratory data showed positivity for anti-nuclear
      antibody and anticardiolipin beta 2 glycoprotein I antibody, and the plasma level
      of renin activity (PRA) was abnormally high. Chest X-ray and UCG revealed massive
      pericardial effusion. On the second hospital day, she was operated on for
      pericardiodiaphragmatic fenestration. The volume of pericardial effusion amounted
      to more than 2000 ml. Post operative malignant hypertension persisted. Laboratory
      data showed thrombocytopenia, hemolytic anemia, and acute renal failure. We
      diagnosed scleroderma renal crisis (SRC) associated with antiphospholipid
      syndrome. Following the initiation of angiotensin converting enzyme inhibitor
      (ACE-I) combined with calcium antagonist and alpha-one blocker, her blood
      pressure and PRA decreased. She also had been treated with aspirin 81 mg daily.
      These therapies were effective in recovering the platelet count and stopped the
      progression of anemia and renal failure. Although either the finding of large
      pericardial effusion or SRC is associated with poor prognosis in PSS, this case
      has had a good clinical course. In this case, the findings suggested that anti
      phospholipid antibody may have contributed to the pericarditis and SRC.

PMID- 9654915
TI  - [Membranoproliferative glomerulonephritis-like lesion with fibrillary deposition
      associated with multicentric Castleman's disease].
AB  - We report a case of a 65-year-old man presenting with multicentric Castleman's
      disease (MCD) accompanied by membranoproliferative glomerulonephritis-like lesion
      with fibrillary deposits. The lesion was characterized by highly organized
      ultrastructual deposits that were negative for Congo-red stain and for
      immunoglobulin, light chain and C3. Thus, this renal lesion was considered
      histologically to be fibrillary glomerulonephritis presenting by light microscopy
      as mesangiocapillary glomerulonephritis. To our knowledge, among the limited
      number of cases of renal lesion associated with MCD ever reported, this is the
      first case of a biopsy-proven fibrillary glomerulonephritis. Serum interleukin 6
      (IL-6), known as an indicator of MCD activity and as an autocrine growth factor
      for mesangial cells, was chronologically measured. Augmentation of urinary IL-6
      simultaneously with that of extra renal symptoms of MCD and associated renal
      disease may indicate an underlying role of this cytokine in the present case.
      Failure to detect of IL-6 in the glomeruli may support the notion that IL-6 is
      derived from extrarenal lymphonodi, and not to an in situ product of the
      glomeruli. However, it may have been related to glomerular injury.

PMID- 9654916
TI  - [A case of Bartter's syndrome with chronic renal failure due to chronic
      interstitial nephritis].
AB  - We report a case of 45-year-old women with Bartter's syndrome and concomitant
      renal dysfunction. In 1986, the patient demonstrated muscle weakness and serum
      potassium levels as low as 1.1 mEq/l. She was suspected of having Bartter's
      syndrome because of hypokalemia, metabolic alkalosis, hyperreninemia,
      hyperaldosteronism and normotension. Pretibial edema developed in 1989 for which
      she received 40 to 100 mg/week of furosemide intermittently for the next 5 years.
      Her serum potassium level ranged from 1.5 to 3.9 mEq/l. In 1991, her serum
      creatinine level rose to 2.1 mg/dl, then continued to increase gradually. She was
      admitted to our hospital in 1994 for evaluation of the renal dysfunction.
      Decreased creatinine clearance (44 ml/min) and a defect in urinary concentrating
      capacity (Fishberg's test, 370 mOsm/kg.H2O) were detected. Renal biopsy revealed
      juxtaglomerular cell hyperplasia. These findings resulted in the diagnosis of
      Bartter's syndrome. The renal biopsy also showed diffuse interstitial fibrosis
      and marked tubular atrophy. We postulate in this case that long-term hypokalemia
      due to Bartter's syndrome and the administration of furosemide led to chronic
      interstitial nephritis and renal dysfunction.

PMID- 9654917
TI  - Endoventricular patch plasties with septal exclusion for repair of ischemic left
      ventricle: technique, results and indications from a series of 781 cases.
AB  - Most cases of left ventricular aneurysms undergo operation through resection of
      the exteriorized dyskinetic area with longitudinal suturing of the opening and
      this technique has been considered by cardiologists (Froehlich et al) to bring no
      improvement to the morphology and performance of the left ventricle. Some
      technical modifications have been adopted, such as the septal plicature (Cooley)
      or circular suturing of the opening (Jatene). Since 1984 our team has used an
      endoventricular patch, sutured over the contractile area and excluding the
      akinetic non-resectable scars, bringing a significant and calculable improvement
      to the left ventricular function. This technique of left ventricular
      reconstruction (LVR), called endoventricular circular patch plasty (EVCPP) has
      been already used on more than 750 patients (May 97). Clinical and echographic
      data for each case are completed by right catheterisation with measurement of the
      cardiac output, pulmonary arterial pressures (PAP) and programmed ventricular
      stimulation (PVS), in order to detect eventual ventricular tachycardia (IVT).
      During left heart catheterisation, the morphology of the left ventricle (LV) is
      studied on right and left anterior oblique incidences and the LV ejection
      fraction (EF) is checked globally (GEF) and especially in its contractile portion
      (CEF). After surgery, a hemodynamic study associated with a PVS, is carried out
      during the first post-operative month, and again after one year. Results were
      clinically satisfactory in more than 90% of cases (8.9% of NYHA III-IV), and in
      more than 90% of cases with ventricular arrhythmia with the hemodynamic
      persistent EF at one year, superior to the pre-operative CEF. Thus we have to
      propose the following indications: Elective: This ventricular reconstruction can
      be recommended for ventricular aneurysms or akinesias with angina, arrhythmias or
      attacks of cardiac insufficiency, when GEF > 30% and CEF > 40%. The operative
      mortality rate varies from 1,5 to 3%, which is better than allowing natural
      evolution. Mandatory: In emergency, when safe immediate circulatory assistance or
      a cardiac transplant is unavailable, LVR can give hope for survival to more than
      80% of patients, whereas natural evolution is without hope. Finally the operative
      indication is uncertain in two contrasting circumstances: In asymptomatic
      patients when hemodynamic and angiographic examinations after myocardial
      infarction show left ventricular dyskinesia. If GEF is below 40% and CEF below
      50%, it seems wise to propose LVR in order to prevent unfavourable evolution. In
      end-stage ischemic cardiomyopathies, if the EF is below 20%, CEF is below 30%,
      cardiac output is below 1.5 l, and the mean pulmonary pressure is above 25, then
      a cardiac transplant should be considered. EVCPP with septal exclusion is a safe
      technique and easily reproduced when associated with coronary revascularization
      as far as practicable, then EVCPP improves the ventricular function. When
      associated with sub-total endocardectomy, then EVCPP allows excellent control of
      VA.

PMID- 9654918
TI  - Malignant melanoma of the chest wall with an unknown primary lesion.
AB  - We report herein the case of a 66-year-old man who underwent resection and
      reconstruction of the chest wall due to the presence of a malignant melanoma
      without a detectable primary lesion. The patient was discharged in good condition
      after receiving chemotherapy but eventually died of multiple bone metastases 2
      years after surgery. Throughout the postoperative course, there were no specific
      symptoms or findings suggesting the presence of a primary lesion. It was
      considered likely that the primary tumor was resolved by spontaneous regression
      after chest wall metastasis had been established.

PMID- 9654919
TI  - "Hexatuple" coronary bypass with in situ arterial grafts.
AB  - A fifty-seven year old male patient with severe three-vessel coronary artery
      disease underwent successful coronary bypass surgery in six vessels utilizing the
      in situ left internal thoracic and right gastroepiploic arteries. Each arterial
      conduit was anastomosed sequentially to as many as three coronary vessels
      respectively. Surgical results were excellent and the patient continues to do
      very well. A postoperative angiogram showed well-working arterial conduits
      without any anastomotic problems. Multiple sequential anastomoses of the in situ
      arterial conduits, although rather technically demanding, can provide better long
      term results in patients requiring multiple coronary revascularization. When
      sequential anastomoses of the right gastroepiploic artery are being considered,
      the length and caliber of the artery should be evaluated by an angiogram since it
      varies in size compared to the internal thoracic artery.

PMID- 9654920
TI  - Thoracic and cardiovascular surgery in Japan during 1996: annual report by the
      Japanese Association for Thoracic Surgery. Committee of science.

PMID- 9654921
TI  - [Removal of the endocardial pacemaker leads--experience with 16 leads in 10
      patients].
AB  - Recent advances in pacemaker leads have contributed to the improvement of their
      stability at the anchored sites. However, we sometimes have difficulty in
      removing them. We have experienced the removal of 16 leads in 10 patients (male:
      7, female: 3) in the last 5 years. The age of patients ranged from 48 to 87
      years, and the average was 60. The reasons for the removal were as follows;
      pocket infection in 6 cases, sepsis in 1 case, ischemic skin erosion in 1 case,
      retained fractured ventricular lead in 1 case, fracture of Accufix atrial lead in
      1 case. The methods of removal consisted of using the removal kit, the snare or
      the basket snare transvenously, direct surgical approach or a combination of
      them. We used the removal kit alone in 12 electrodes (6 atrial, 6 ventricular),
      and removal of 5 atrial and 3 ventricular leads were successfully by this method
      only. The removal of 4 leads by kits alone failed, so that 2 ventricular leads
      were removed transvenously, one atrial and one ventricular lead were removed
      surgically, and 1 ventricular lead was left untreated. Finally, we were able to
      remove 15 of 16 leads (93.3%) successfully. This experience indicates that these
      interventions should be performed as less invasively as possible, yet we should
      give an explanation to the patients as to the options we may employ when we have
      failed in the intended procedure.

PMID- 9654922
TI  - [Early recovery after valvular heart surgery].
AB  - There have been published not a few reports concerning the early recovery from
      heart surgery. But most of them were restricted in CABG cases. We report our
      efforts and its results about the early recovery from valvular heart surgery. To
      make a contribution to the early recovery we have made some efforts since 1995,
      including normothermic perfusion, low-dose fentanyl and introduction of terminal
      warm blood cardioplegia. As the results, the tracheal intubation period was
      shortened from 12.6 +/- 5.3 (hour) to 6.7 +/- 4.1. The number of the cases who
      had tracheal extubation in the operative day increased from 27% to 84%. The
      postoperative cardiac function was satisfactory and there were no abdominal or
      neurologic disturbances among the patients those who were entered into the early
      recovery protocol. We obtained satisfied early recovery in safe after valvular
      heart surgery.

PMID- 9654923
TI  - [Evaluation of the growth of a new pulmonary trunk after the reconstruction of
      right ventricular outflow tract without using an external conduit].
AB  - To evaluate the growth of a pulmonary trunk reconstructed without an extracardiac
      conduit, the hemodynamics and diameter of a new pulmonary trunk were measured in
      5 patients from the right ventriculogram and MRI at postoperative follow-up
      periods. There were tetralogy of Fallot with pulmonary atresia in two patients,
      tetralogy of Fallot with single coronary in one, truncus arteriosus type I in one
      and transposition of the great arteries with ventricular septal defect and
      pulmonary stenosis in one. The age at operation ranged from 26 days to 4.5 years.
      The posterior wall continuity of the right ventricle and pulmonary artery was
      established by the direct pulmonary-right ventricular anastomosis in three
      patients and by the interposition of the left atrial appendage in two.
      Postoperative follow-up periods ranged from 2 years and 6 months to 3 years and
      10 months (median: 2 years and 11 months). In four of them, the postoperative
      right ventricular to aortic or left ventricular systolic pressure ratios were
      less than 0.4 without any significant systolic pressure gradients between
      pulmonary artery and right ventricle. In these four patients, the diameters of
      the reconstructed pulmonary trunks grew from 10-18 mm to 18-21 mm
      postoperatively. These diameters were more than 100% of normal values. In the
      remaining patient with tetralogy of Fallot and single coronary artery, the
      obstruction of the new pulmonary trunk by a bulged left atrial appendage, which
      was used as the posterior wall, was observed on the right ventricular outflow
      tract reconstruction without an extracardiac conduit has growth potential in the
      future.

PMID- 9654924
TI  - [Surgical stabilization of multiple rib fractures successfully achieved with the
      use of long metalic plates].
AB  - Surgical stabilization of multiple rib fractures in 5 male patients was
      successfully achieved with the use of orthopedic A-O metalic plates, which are
      called reconstruction plates. In each patient, we prevented deformity of the rib
      cage and flail chest which frequently occurs after multiple rib fractures. Three
      of these patients received emergency operations because of severe
      hemopneumothorax and flail chest due to crushing injuries to the chest. They were
      treated by the standard thoracotomy, hemostasis of intrapleural bleeding, and
      stabilization of fractured ribs with reconstruction plates, in addition two of
      the patients underwent a single lobectomy to control the pulmonary hemorrhage.
      Another two patients were treated with mechanical ventilation and closed-tube
      thoracotomy following the chest trauma because their thoracic bleeding from
      drainage tubes was tolerable. But flail chest and respiratory insufficiency did
      not improve, in spite of positive controlled ventilation as a mode of internal
      pneumatic stabilization. Then surgical stabilization of the fractured ribs with
      these plates was carried out ten to twelve days after the accidents in each case.
      All patients tolerated the surgical procedures well and were successfully removed
      from the respirator, demonstrating complete stability of the chest wall. The long
      metal reconstruction plates with many perforations were very useful for the
      external fixation of segmentary fractured ribs as an external brace. This was
      because they were long enough to cover the whole length of the fractured ribs and
      moderately soft enough to be appropriately bent or twisted by hand at the time of
      operation. Moreover a number of holes in it allowed the suture to pass through
      the plate and rib, avoiding displacement of the prosthesis. This is the first
      report which describes the usefulness of orthopedic reconstruction plates for the
      stabilization of multiple rib fractures.

PMID- 9654925
TI  - [A case of congenital partial pericardial defect and anomaly of phrenic nerve
      with cystic bronchiectasis].
AB  - Congenital partial pericardial defect is a rare anomaly that causes no symptoms
      and is often noticed by chance at autopsy or thoracotomy. During an operation on
      a patient with bronchiectasis, a partial pericardial defect and anomaly of left
      phrenic nerve were found incidently. A 58-year-old man complaining hemoptysis was
      referred to our hospital for surgical treatment of the left cystic
      bronchiectasis. During a thoracotomy, a partial pericardial defect was noticed.
      Moreover the left phrenic nerve could not be found within the operative field. We
      performed left pneumonectomy without repair of pericardial defect, and the
      patient had a satisfactory postoperative course. A relationship was suggested
      between congenital pericardial defect and the anomaly of the phrenic nerve.

PMID- 9654926
TI  - [Primary liposarcoma of the anterior mediastinum--case report and review of
      literature].
AB  - A 76-year-old male with anterior mediastinal tumor was admitted to our hospital.
      He had undergone mediastinal lipoma surgery 3 years earlier. The tumor was
      excised surgically. Microscopic sections of the tumor showed liposarcoma composed
      of myxoid tissue. Further examination of prior specimens taken from this patient
      proved this case to be a recurrence of liposarcoma. Poorly differentiated tumors,
      which pathologically tend to be more cellular with less fat per cell component,
      are likely to have high CT numbers. But CT number is not sufficient to
      distinguish well-differentiated liposarcoma from benign lipoma.

PMID- 9654927
TI  - [A case of surgical treatment for Loffler's endomyocarditis].
AB  - We performed surgical treatment in a case of loffler's endocarditis. The patient
      was a 32-year-old male whose first symptom was easy fatigability. Blood count
      showed eosinophilia (eosinocyte count 6720/mm3). Echocardiography and
      vetriculography showed thickened bilateral endocardium and extension disturbance.
      We diagnosed this case as loffler's endocarditis and performed surgical treatment
      because medical treatment was unsuccessful. Removal of the thrombus the bilateral
      ventricles, endocardectomy and mitral valve replacement were performed.
      Endocardectomy required close attention because the border between thickened
      endocardium and normal myocardium was obscure. The patient survived surgery, but
      postoperative echocardiography (15 days) revealed slightly thickened endocardium
      of the right ventricle. He died of left heart failure 1 month after surgery. At
      that time, eosinocyte count was 110,000/mm3.

PMID- 9654928
TI  - [An emergency aortic valve replacement for cardiogenic shock patient with severe
      aortic stenosis and regurgitation using percutaneous cardiopulmonary support].
AB  - The percutaneous cardiopulmonary support system (PCPS) was used in a 64-year-old
      woman with cardiogenic shock due to sustained ventricular fibrillation (Vf)
      caused by severe aortic stenosis and regurgitation. The Vf attack was resistant
      to cardioversion and adrenaline for lack of left ventricular support by PCPS. She
      was transported to the operation theater with PCPS in situ and emergency aortic
      valve replacement was performed. Although preoperative cardiac resuscitation time
      was long (35 minutes), she was discharged from the hospital on foot without any
      neurological complications on 84th postoperative day. Because PCPS does not
      decrease left ventricular systolic stress in poorly contracting dilated heart,
      early surgical treatment is needed in patients with severely damaged heart.

PMID- 9654929
TI  - [Myxoid leiomyosarcoma of the esophagus].
AB  - A 34-year-old male patient with epigastralgia was found to have an esophageal
      submucosal tumor based on an endoscopic evaluation 6 years previously. Because an
      unusual appearance composed of a heterogeneous solid area and a cyst area on the
      endoscopic ultrasonogram and the increased size of the tumor on esophagograms
      over the past 3 years were suggestive of a malignant character, an operation was
      thus indicated. The tumor, which measured 3.5 x 2.5 x 2.0 cm in size, was
      enucleated using videoassisted thoracic surgery and was diagnosed to be a very
      rare myxoid leiomyosarcoma with a thorough pathologic examination. To our
      knowledge, this is only the second case of esophageal myxoid leiomyosarcoma
      reported in the literature. We thus consider this case, which demonstrated an
      unique appearance on an endoscopic ultrasonogram, to possibly be beneficial to
      the overall diagnostic analysis of esophageal submucosal tumors.

PMID- 9654930
TI  - [A case report of recurrent self inserted needle in heart].
AB  - A 17-year-old female who had, on two occasions, inserted a total of 7 needles
      into her heart and chest wall, resulting in autolesion on both occasions, was
      examined. On the first occasion, because the needle end was recognizably
      protruding from the right ventricle, we successfully removed the needle without
      using ECC. No complications arose prior to discharge, after which she regularly
      visited the psychiatric department for treatment. Two months after discharge, she
      again inserted needles into her chest wall and was admitted to hospital. At that
      time, five needles were evident in the chest wall. During preparation for removal
      of the needles under local anesthetic, she escaped from the room. When found in a
      ward several hours later, six needles were embedded in her chest wall, the sixth,
      most recently inserted needle was an injection needle. Due to the depth to which
      the needle had been inserted in the heart, neither the point nor end were
      visible, and thus the needle had to be removed using ECC and fluoroscopy.

PMID- 9654931
TI  - [Acute mediastinitis due to esophageal perforation--a case report].
AB  - A 55-year-old female consulted her family physician because of pharyngeal
      discomfort after eating a fish. She underwent rigid fiberscopy and was pointed
      out a fish bone. Family physician failed to extract the bone and the patient was
      referred to our hospital. However, there was no fish bone in the esophagus when
      she underwent second rigid fiberscopy. After eight days she complained of dyspnea
      and was referred to our hospital again. Chest X ray film showed marked
      enlargement of the mediastinum and she was diagnosed as acute mediastinitis. She
      underwent mediastinal drainage by thoracotomy. So tiny perforation was found in
      cervical esophagus by endoscopy that primary suture was not done. After two
      months' follow up with intravenous hyperalimentation, there was still esophageal
      perforation. She underwent the second operation of primary closure with
      reinforcement using sternocleidomastoid muscle. Two weeks after the second
      operation esophagogram still showed a fistula. So she received injections of
      alprostadil and factor XIII. One month after the injections esophagogram showed a
      diverticulum without leakage.

PMID- 9654932
TI  - [Spontaneous splenic rupture after mitral valve replacement for infective
      endocarditis].
AB  - We report a successful treatment of massive bleeding due to spontaneous splenic
      rupture after mitral valve replacement. A 61-year-old man was admitted to our
      hospital for intermittent high fever. An echocardiogram demonstrated a large
      vegetation on the posterior cusp of the mitral valve and mitral regurgitation of
      moderate degree. Staphylococcus epidermidis was cultured from his arterial blood.
      He underwent a mitral valve replacement after 3 weeks of antimicrobiological
      therapy with penicillin G crystalline and minocycline hydrochloeide. The patient
      fell into hemorrhagic shock on postoperative day 11 after complaining dull pain
      on his left upper abdomen for 3 days. A computed tomography demonstrated a
      splenic rupture and massive hematoma in the retroperitoneum. A splenic arterial
      embolization was done before splenectomy. The blood and clot of 2800 g were
      sucked from peritoneal and retroperitoneal cavities. There were no mycotic
      aneurysms nor abscess but the torn capsule on the swelled and partially necrotic
      spleen. The patient discharged uneventfully on postoperative day 43. Infective
      endocarditis frequently causes splenic infarction but rarely splenic rupture.
      Anticoagulation therapy after mitral valve replacement might have emphasized the
      bleeding in the patient.

PMID- 9654933
TI  - [A case of rupture of the diaphragm caused by the plication for diaphragm
      eventration].
AB  - A 71-year-old woman, in whom the herniation of right-sided diaphragm was
      diagnosed, was admitted to our hospital on ambulance car complaining of
      increasing right-sided chest pain and worsening of dyspnea. She was given
      emergency laparotomy. The transverse colon and omentum pushed the liver backward.
      The tight adhesion between transverse colon and diaphragm was released by using
      thoracotomy additionally. In pleural cavity, there was prolapsing transverse
      colon which was not covered with peritonium and was caused by the rupture of
      right-sided diaphragm. The necrotic transverse colon was resected about 30 cm
      length. We considered that the rupture was caused not by external injury but by
      inflammation after plication for diaphragm eventration three years and ten months
      before.

PMID- 9654934
TI  - [A case of the pulmonary thrombosis caused by unilateral pulmonary artery
      occulusion test].
AB  - A 71-year-old male, diagnosed as lung cancer, underwent unilateral pulmonary
      occulusion test. Through the guidewire, 7.5 Fr thermodilution catheter with
      occlusion balloon was introduced to the left pulmonary artery from the right
      internal jugular vein. Heparinized physiological saline solution was injected
      into the distal site of the occulusion. The occulusion time was 15 minutes.
      Pulmonary artery pressure and wedge pressure were within normal range. Soon after
      the examination, the pulmonary arteriogram (PAG) showed the defect of the branch
      to the lingular segment and the lower lobe. We made a diagnosis of pulmonary
      thrombosis. Three days after the administration of urokinase and heparin, both
      pulmonary perfusion scintigram and PAG exhibited the reperfusion to these areas.
      After the thrombolytic therapy was accomplished, antithrombin III and protein C
      in the serum showed within normal range. It was possible that the damage on the
      intima due to the thermodilution catheter or the guidewire and the following
      blood congestion by the pulmonary artery occulusion caused the thrombosis.

PMID- 9654935
TI  - [Mediastinoscopic diagnosis and drainage of pericardial diverticulum--a case
      report].
AB  - A 38-year-old male was suspected of having an enlarged pretracheal lymph node on
      chest CT scan. At mediastinoscopy, a cystic lesion was recognized, and showed
      repeated dilatation and contraction synchronously with the cardiac beat.
      Pneumopericardium was demonstrated by intraoperative pneumocystography. The
      cystic lesion was diagnosed as pericardial diverticulum. The diverticular wall
      was partially resected for drainage of the pericardial fluid. Mediastinoscopy as
      a less invasive procedure may be useful for the differential diagnosis of
      adenopathies, and in case of lesion such as a small pericardial diverticulum may
      allow treatment.

PMID- 9654936
TI  - [Decortication in chronic thoracic empyemas--a report of three cases].
AB  - Three cases of chronic thoracic empyema treated by decortication are reported
      with special reference to the indications for surgery. The first patient was a 68
      year-old man who had right chronic thoracic empyema with a bronchopleural
      fistula. He underwent open thoracostomy, and decortication was performed after 8
      months. The second patient was a 74-year-old man who had right chronic empyema
      without bronchopleural fistula. Open thoracostomy was also performed and
      decortication was done after 2 months. Postoperative pulmonary function was
      significantly improved in both patients. The third patient was a 66-year-old man
      who had left chronic empyema with a bronchopleural fistula. He underwent open
      thoracostomy and left lower lobectomy, and then decortication and the omental
      pedicle flap method were performed after 4 months. All three patients are still
      doing well currently. It is concluded that decortication significantly improves
      pulmonary function in properly selected patients, and that computed tomography is
      helpful for assessing the re-expansion ability of the collapsed lung.

PMID- 9654937
TI  - [Acute ventricular septal perforation in a patient with autoimmune hemolytic
      anemia].
AB  - A 71-year-old woman with autoimmune hemolytic anemia underwent an emergency
      endocardial patch repair for ventricular septal perforation after acute
      myocardial infarction. Use of washed red blood cells was effective in averting
      hemolytic crisis throughout perioperative period. In spite of improvement of her
      hemodynamics, liver dysfunction which had been present preoperatively
      deteriorated after the operation. Finally she died of hepatic failure on the 21st
      postoperative day. Deterioration of liver function could not be associated with
      autoimmune hemolytic anemia. To date, little information is available concerning
      the influence of cardiopulmonary bypass on hemolysis in patients with autoimmune
      hemolytic anemia. Therefore, prudent management and use of washed red blood cells
      transfusion would prevent hemolytic aggravation even in open heart surgery.

PMID- 9654938
TI  - [A case report of aortic valve replacement following ruptured aneurysm of the
      sinus of Valsalva with bicuspid valve].
AB  - Only three cases of the combination of bicuspid aortic valve and ruptured
      aneurysm of the sinus of Valsalva, associated with previously repaired
      coarctation of aorta, have been reported. A twenty-year-old man with a sudden
      onset of CHF due to ruptured aneurysm of the sinus of Valsalva underwent
      intracardiac repair by direct closure of the sinus Valsalva in combination with
      patch closure of a subarterial VSD. Although, no AR was detected preoperatively,
      massive regurgitation occurred after the repair due to subsequent failure of
      aortic valve coaptation in the present of the bicuspid aortic valve, which was
      not diagnosed preoperatively. Aortic valve replacement with SJM 25 mm was
      successfully performed.

PMID- 9654939
TI  - [Two cases of coronary artery aneurysm including one case of the left main
      coronary artery aneurysm].
AB  - We report two cases of coronary artery aneurysm including one case of the left
      main coronary artery aneurysm. The coronary angiogram of one patient, a 68-year
      old male, having anterior chest pain on exertion, revealed left anterior
      descending coronary artery (segment 6) aneurysm of 7 mm in diameter with 90%
      stenosis distal to the aneurysm and 75% stenosis in the right coronary artery
      (segment 2). The coronary angiogram of another patient, a 69-year-old female,
      having chest pain unrelated to exertion, revealed left main coronary artery
      aneurysm of 25 mm in diameter and delayed filling of contrast medium into the
      left anterior descending coronary artery. We decided to operate by the reason of
      not only significant coronary artery stenosis but risks of myocardial infarction
      due to embolization into distal coronary arteries and rupture of the aneurysm. We
      performed coronary artery bypass graftings using the great saphenous veins and
      closure of the coronary arteries running into and out the aneurysm under
      cardiopulmonary bypass. It is recommended that ligation of the coronary arteries
      connecting to the aneurysm or resection of the aneurysm followed by coronary
      artery bypass grafting is performed before developing myocardial infarction or
      rupture of aneurysm.

PMID- 9654940
TI  - [A study on chemical and immunochemical properties and chemotaxonomy of
      lipopolysaccharides of Vibrionaceae, in particular Vibrio cholerae and V.
      parahaemolyticus].

PMID- 9654941
TI  - [DNA vaccination--current status and future prospect--a new approach for
      controlling infectious diseases].

PMID- 9654942
TI  - [The front line of the study on human oral spirochetes].

PMID- 9654943
TI  - [Dextranase of Streptococcus mutans].

PMID- 9654944
TI  - [Phylogenetic classification of plant pathogenic mycoplasma].

PMID- 9654945
TI  - Prevention of occupationally acquired infections among heath-care workers.

PMID- 9654946
TI  - The long QT syndrome.
AB  - The LQTS is no longer the rare "zebra" whose purpose is to ensure that trainees
      recall that deafness and sudden cardiac death may be related (Jervell and Lange
      Nielsen syndrome). Over the past 10 to 20 years, the number of cases of inherited
      LQTS (Romano-Ward syndrome) has increased dramatically. It is doubtful that this
      reflects a true increase in incidence of disease due to a greater rate of
      sporadic gene mutations occurring in the heart or because of a rising incidence
      of consanguinity. Rather, the "incidence" of LQTS has risen because of the
      emerging awareness of and respect for this electrical malady in the heart.
      Understanding the principal elements of the LQTS, knowing the types of
      presentations, and being able to identify its presence electrocardiographically
      will allow the astute physician to expose this silent killer.

PMID- 9654947
TI  - Macrolides: clarithromycin and azithromycin.

PMID- 9654948
TI  - Urticaria.

PMID- 9654949
TI  - Case 1 presentation of bizarre behaviors.

PMID- 9654950
TI  - Case 2 presentation of increasing pallor, fever and malaise.

PMID- 9654951
TI  - Case 3 presentation of facial bruises.

PMID- 9654952
TI  - Amniotic bands.

PMID- 9654953
TI  - Yersinia enterocolitica.

PMID- 9654954
TI  - [Multidrug-resistant tuberculosis in Romania].

PMID- 9654955
TI  - [Disability in pulmonary tuberculosis in the city of Bucharest].
AB  - The authors analyse the invalidity (new retreated cases) for pulmonary
      tuberculosis, in a period of 9 years (1986-1994), comparing the time before and
      after the December 1989 Revolution, by making a screening in 2 districts of
      Bucharest which, by number of population and incidence of tuberculosis, are
      representative for Bucharest. In the analyzed time, in Romania was noticed a
      three times increase of tuberculosis invalidity, especially due to pulmonary
      tuberculosis. In the two districts of Bucharest, in the 1991-1994 period compared
      to the 1986-1990 period, an increase in tuberculosis invalidity was noticed in
      men and women, the most affected age group being the one with the greatest work
      involvement (age 41 to 50). A great percentage of cavitary tuberculosis was
      registered (89%), with an increase of bilateral cavitary lesions frequency from
      28% to 36% in the last 4 years. In the same time, the amount of deaths among the
      retreated patients increased, with a reduction of number of patients returning to
      work. All the data show a worsening in the last period (1991-1994) of the
      tuberculosis endemic and invalidity by this disease, probably due to the social
      and economical factors.

PMID- 9654956
TI  - [Initial experiments with controlled assisted ventilation by nasal mask in
      exacerbated chronic respiratory failure in chronic obstructive
      bronchopneumopathies].
AB  - The authors are presenting the first cases in Romania in which volumetric
      ventilators Monnal D type were used for external ventilatory assistance on nasal
      mask of the chronic obstructive pulmonary diseases in exacerbation. The paper
      reviews the problems issued during the use of ventilators in 5 chronic patients,
      with numerous previous admittances in our clinic, as well as the latest news in
      the field of modern therapy of COPD.

PMID- 9654957
TI  - [The epidemiological profile and current evolutionary trends in tuberculosis in
      adolescents (15-19 years old) in the capital].
AB  - In Bucharest, the increasing TB incidence in the age group of 15 to 19 years till
      100.11/100000 in 1996 has to become a concerning matter. The study of 585 cases
      aged 15 to 19 registered in Bucharest between 1991 and 1995 (more than 2/3 of all
      the cases in that period) revealed the important proportion of secondary TB
      (67.4%), as well as the frequency of pleural involvement (25.6%). The main
      discovering methods remain the examination of symptomatic cases (78.6%) and
      epidemiological inquiry (10%). The fact that 85% of the bacteriological confirmed
      cases had positive sputum specimens in microscopy confirms the idea of
      discovering the patients in advanced stages of disease, as well as
      epidemiological signification. Almost 50% of the ill teen-agers belong to
      families with low living status. At this age group we found an important degree
      of recovery after chemotherapy (82% rate of healing in the first year).

PMID- 9654958
TI  - [Therapeutic management in a case of pleural empyema complicated by ARDS].

PMID- 9654960
TI  - [The management of bronchial asthma in adults].

PMID- 9654959
TI  - [Bilateral multifocal pulmonary leiomyomatosis].
AB  - A case of diffuse primary pulmonary leiomyomatosis with a 24-years-old
      asymptomatic woman having a pulmonary radiological aspect of miliary
      dissemination 3 years after a myomectomy for sub-serous uterine fibroma. The
      diagnosis was established after a surgical pulmonary biopsy. The case presented
      certain peculiar features: a young woman; the inter-relation between pulmonary
      leiomyomatosis and the operated sub-serous uterine fibroma; the aggravating
      factor--the pregnancy; a confirmed probably hormonal cause (hyperestrogenemia); a
      progressive aggravating evolution.

PMID- 9654961
TI  - [Delayed-action theophyllines with "once a day" administration--a new therapeutic
      tool in asthma and COPD].

PMID- 9654962
TI  - [Education for health--smoking. Testing the knowledge and behavior of some socio
      professional groups--students, parents and teachers].

PMID- 9654964
TI  - [The current epidemiological aspects of osteoarticular tuberculosis].

PMID- 9654965
TI  - [The chronology and diagnostic round of patients operated on for bronchopulmonary
      cancer].
AB  - 37 patients with certified diagnosis, operated for lung cancer (LC) in The
      Central Military Hospital Bucharest, during six months period (October 1st 1996
      June 1st 1997). It was a retrospective study on the patients medical files. Sex
      distribution, postsurgical staging and histological type were studied. We
      calculated the following delays: 1. Between the first medical examination and the
      first suspicion (chest X-ray): 6 +/- 3 days; 2. Between the first medical
      examination and first hospital admission: 14 +/- 11 days; 3. Between the first
      hospital admission and the first admission in surgical units: 43 +/- 23 days; 4.
      Between the first admission in surgical units and surgery: 59 +/- 26 days; 5. The
      delay until bronchoscopy: 23 +/- 16 days; 6. The delay until the CT examination:
      26 +/- 16 days; 7. Between the first medical examination and the surgery: 78 +/-
      30 days. These delays were correlated with the specialty profile of the services
      which referred the patients: pulmonology, internal medicine, oncology or primary
      services. CONCLUSION: 1. Most patients come from pulmonology units (22 out of 37
      patients); 2. There are significant delays until bronchoscopy and CT scan, the
      availability of these services is still limited; 3. The primary care medical
      network is still inefficient in early diagnosis of LC; 4. The overcrowding of
      thoracic surgery unit (scheduling for surgical intervention). All of these are
      arguments for developing more efficient and faster circuits of LC diagnosis,
      especially for high risk patients.

PMID- 9654966
TI  - [The evaluation parameters of the long-term treatment efficacy of theophylline in
      the child with bronchial asthma].
AB  - In the past decade the use of theophylline was less extensive because of its
      narrow therapeutically index and due to its side effects. The widening of
      possibilities of monitoring the treatment by serum level determination, the
      introduction of slow release formula, and the demonstration of antiinflammatory
      effects made theophylline to become actual again. Theophylline is indicated for
      the chronic treatment of asthma in association with other medication. The authors
      study the efficacy and serum level of theophylline in 13 children with asthma who
      received slow release theophylline in a dosage of 15.2 mg/body weight/24 hours in
      average, administered 3 times a day. The efficacy was estimated by a clinical
      score and the serum level was determined by isotopic mass spectrometry with 15N
      theophylline as internal standard. After a period of at least 2 months of therapy
      it was recorded the amelioration of clinical score (with 5.09 points, that
      represents 36.3% of the maximum initial score) and the reducing of circadian
      variation of peak expiratory flow from 27% to 15%. The serum level of
      theophylline was of 8.25 +/- 4.16 micrograms/ml at 4 hours after administration
      and of 5.69 +/- 2.6 micrograms/ml at 8 hours after administration of the last
      dose. The individual values less than 5 micrograms/ml was found in 3 of 13
      children at 4 hours and in 7 of 13 children at 8 hours after the last dose. There
      were no patients with toxic serum levels of theophylline (> 20 micrograms/ml).
      The correlation between serum level of theophylline and the dosage was weak both
      at 4 hours (r = 0.054) and 8 hours (r = 0.229) after the last dose. At the same
      dose there were found high interindividual variations. These findings are
      arguments for the usefulness of determination of serum levels of theophylline,
      that together with clinical and functional parameters allowed the
      individualization of the dosage.

PMID- 9654967
TI  - [Pulmonary fibrosis and systemic sclerosis].

PMID- 9654968
TI  - [Pulmonary alveolar microlithiasis--a clinical case].
AB  - A new case of alveolar microlithiasis is reported, demanding for the diagnosis
      besides the radio-clinical investigations, complete respiratory function tests,
      also the pathologic proof. Authors recall the diagnostic approach and our present
      ignorance of the pathogenesis of this curious entity; no valid therapy is
      presently able to check the relentless course toward progressive respiratory
      failure.

PMID- 9654969
TI  - [The pulmonary syndrome produced by hantaviruses].

PMID- 9654970
TI  - [The quality-of-life study in oncology with reference to bronchopulmonary
      carcinomas].

PMID- 9654972
TI  - [Recommendations for bronchoscopic treatment of tracheobronchial occlusions,
      stenoses and mural malignant tumors. German Society of Pneumology "Quality
      Assurance in Bronchology" Working Group].

PMID- 9654973
TI  - [Endobronchial chondroma--bronchoscopic resection or thoracic surgery
      intervention?].
AB  - Endobronchial chondromas as a rare form of benign tumors of the bronchial tree
      lead not only to diagnostic problems because of the unspecific often latent
      pattern of symptoms, but also to therapeutic difficulties because of the
      macroscopic findings and the poststenotic changes of the bronchial tree and the
      lung parenchyma. In case of a 75-year old female patient the various therapeutic
      possibilities are discussed. The therapy must be individual and consider the
      extent of simultaneous lung changes and the general criteria of operability in
      thoracic surgery.

PMID- 9654974
TI  - [Successful therapy of pulmonary aspergillosis in a patient with non-Hodgkin
      lymphoma].
AB  - ANAMNESIS AND CLINICAL PICTURE: A 65-year old male with non-Hodgkin lymphoma
      developed severe invasive pulmonary aspergillosis during a state of leucopenia
      after chemotherapy. INVESTIGATION: The initial manifestation was an infiltration
      in the right upper lobe of the lung, identified by lung scintigraphy as a
      peripheral wedge-shaped loss of perfusion. Both serum and bronchoalveolar lavage
      extreme high titre of Aspergillus antigen were seen as a laboratory indication of
      an invasive aspergillosis. The mould Aspergillus fumigatus was repeatedly
      isolated from bronchoalveolar lavage and bronchial secretion. THERAPY AND
      CLINICAL COURSE: Treatment was started with amphotericin B plus 5-flucytosine
      together with repeatedly bronchoscopic instillation of miconazole followed by
      thoracosurgical intervention with resection of the right upper lobe of the lung.
      Despite prophylaxis by itraconazole, a relapse of invasive aspergillosis occurred
      three months later probably due to persistence of aspergillus fungal elements in
      the left lung. The aspergillosis relapse was treated at first with liposomal
      amphotericin B. After eighteen days of treatment this was changed to a
      combination of 5-flucytosine with oral application of itraconazole, and cure was
      achieved.

PMID- 9654975
TI  - [Epidemiology, clinical aspects and prognosis of severe progressive community
      acquired pneumonia].
AB  - BACKGROUND: Community-acquired pneumonia can lead to acute lung failure
      (parapneumonic ARDS) if the course is very severe. The clinical picture reflects
      a rapidly progressive and potentially fatal respiratory failure. Only occasional
      cases in which the clinical courses of community-acquired pneumonia lead to acute
      respiratory failure have been reported so far. The investigation was based on the
      observation that very severe progressive forms of community-acquired pneumonia
      are at present one of the most frequent conditions triggering ARDS. PATIENTS AND
      METHODS: A total of 66 patients of both sexes with an average age of 34 +/- 11
      years were included in the retrospective investigation. The patients had been
      secondarily referred to the center for further treatment. After admission, the
      further course of the disease was recorded at five defined times (day of
      admission, 2nd day, 7th day, 14th day and day of spontaneous breathing or day of
      death). The degree of disturbance of pulmonary function was registered with the
      scores of Morel and Murray. Further disorders of organ function were evaluated
      with the MOF score according to Goris, the "Definition Multiple disorder of Organ
      Function (DeMOF)" and the appraisal of the severity of the systemic inflammatory
      reaction with the sepsis score according to Elebute & Stoner. RESULTS: The
      duration of preclinical disease was 6 +/- 4 days and the duration of the
      pretreatment in the referring hospital was 10 +/- 10 days. A potential primary
      causative organism (bacteria n = 18, viruses n = 5, "atypical" pathogens n = 6,
      Candida species n = 4) could be isolated in 50% of the patients. A pre-existing
      underlying disease was found in 48% of cases. With a total lethality of 31%, this
      was affected neither by knowledge of the primary causative organism nor by
      previous diseases. The patients who died did so with improved lung function in a
      complete clinical picture of multiorgan failure. At the time of admission, 91% of
      the patients had severe ARDS (Morel III and IV). An improvement of lung function
      could be demonstrated between the day of admission and the second day of
      treatment both with the score according to Morel and according to Murray (p <
      0.05). For the second day of treatment, a difference could be shown between the
      patients who survived and those who died (p < 0.05). Owing to the systemic
      inflammatory reactions, a multiorgan functional disorder was found in 89% of the
      patients. There were the following findings with regard to the prognostic
      predictions from the score used: those who died and those who survived could be
      correctly differentiated with the DeMOF score from the 7th day of treatment and
      the sepsis from the 7th day of treatment and with the score of Goris from the
      14th day of treatment after referral. CONCLUSIONS: The investigation proves that
      the most severe progressive forms of community-acquired pneumonia also occur both
      in patients who have previously appeared to be healthy and in younger patients.
      Despite the use of differentiated treatment measures, these illnesses are subject
      to a relatively high lethality. The results underscore the need for causal
      treatment of systemic inflammatory reaction, which is the most important problem
      in treatment of parapneumonic ARDS.

PMID- 9654976
TI  - [Molecular biology methods in epidemiology of tuberculosis].
AB  - The spread of tuberculosis often remains undetected and development of disease
      may occur years after the primary infection. However, tracing chains of
      transmission is an important task for prevention of new cases, especially for
      multi-drug-resistant tuberculosis. Today, molecular typing methods have become an
      important tool for identification and confirmation of epidemiological links
      between tuberculosis patients in an outbreak situation. Differentiation between
      strains of Mycobacterium tuberculosis also allows to decide between reactivation
      because of treatment failure and superinfection. A growing number of typing
      methods have been developed that differ mainly in their reproducibility and the
      ability to differentiate between isolates closely related at the molecular level.
      Based on further standardisation and automation, molecular typing techniques can
      provide pertinent information for tuberculosis control.

PMID- 9654977
TI  - [Exogenous surfactant administration and partial fluid ventilation. Physiological
      and pathological effects].

PMID- 9654978
TI  - [A new method for imaging ventilation-distribution with 3Helium in magnetic
      resonance tomography].
AB  - BACKGROUND: Conventional 1H-MRI of the lung is restricted by susceptibility
      effects and low proton density: Recently, imaging of lung ventilation in MRI has
      become feasible using hyperpolarised inert gases with a spin of I = 1/2, such as
      3He and 129Xe, as inhalative "contrast agents". New technical developments,
      preclinical and clinical application of this method are described. MATERIALS AND
      METHODS: With optical laser pumping high polarisation rates can be achieved,
      resulting in a high signal-to-noise ratio (S/N). A dedicated application system
      allows accurate administration of 3He boli at different time points during
      inspiration. Thus, dynamic ventilation imaging becomes possible. Prerequisites
      for this method include a dedicated coil as well as a spectroscopy option at the
      MRI system. Fast sequences and low flip angles are employed to comply with the
      relaxation of hyperpolarise 3He in vivo. RESULTS: Overall homogeneous signal
      intensity (SI) represents physiological conditions. Obstructive lung disease is
      associated with generalised or localised signal inhomogeneity. Different time
      constants of specific lung regions are probably responsible for this kind of
      inhomogeneous inspiratory distribution of ventilation. Tumours show a clear
      ventilation deficit, correlating with non-ventilated lung areas. CONCLUSION: 3He
      MRI is a promising new modality for the evaluation of ventilation distribution
      under different pathological conditions. This may include obstructive lung
      disease and assessment of ventilation distribution before and after thoracic
      surgery. Furthermore, evaluation of patients with acute lung failure and
      validation of ventilator settings in anaesthesia may be performed.

PMID- 9654979
TI  - [Alveolar hemorrhage syndrome in sarcoidosis].

PMID- 9654980
TI  - [Cognitive training and strategy behavior: comparative evaluation of 2 cognitive
      training programs].
AB  - Combining a non-comparative with a comparative evaluation, two modern programs
      for fostering inductive reasoning, namely the German version of the "Cognitive
      training for children" by Klauer and Phye (1994; Klauer 1989), and the "DenkMit"
      by Sydow and Meincke (1994), are compared to each other and to a control program
      which intends to enhance aspects of memory instead of inductive reasoning. The
      programs were performed with N = 49 children between six and eight years who had
      been postponed from regular school because of various reasons or who had been
      selected as especially in need for particular interventions from first classes.
      Besides the psychometric test often used for assessing inductive reasoning, i.e.
      three subtests of the German form of the Culture Fair Test by Cattell (Weiss a.
      Osterland 1980), tasks of concept formation were applied for assessing changes in
      strategic behavior of children--a type of task which has been used in connection
      with inductive reasoning since many years. Counter to expectations, the children
      whose memory was trained, showed changes in performance in the psychometric test
      in a similar size as the children whose inductive reasoning was trained. These
      effects are interpreted in terms of special attention directed to the children
      during the intervention situation. Moreover, it was found that despite the
      authors claim to the opposite the DenkMit did not cause any changes in visual
      perception. In contrast to the author's intentions, the "Cognitive Training for
      Children" did cause some substantive changes in the area of visual perception.
      The pattern of results with the concept formation tasks, however, overall
      indicates that the reasoning programs caused some changes in strategic behaviors
      of the children. Although these changes are not very impressive, they cannot be
      attributed to extraneous factors such as special attention.

PMID- 9654981
TI  - [Course and prognosis of anorexia nervosa: catamnesis of 41 patients].
AB  - The purpose of the following study was a multidimensional assessment of the
      course of anorexia nervosa. In our follow-up-study we were able to examine 41 out
      of 51 patients meeting DMS-111 R criteria for anorexia nervosa in our department
      at a mean follow-up of 5.3 years. At the first evaluation the patients were
      characterized by an early age of onset (mean 14.2 years), no or very little
      previous psychiatric treatment, and restrictive eating habits (72.5%); the mean
      age was 15.2 years. At the time of follow-up, the physical outcome was
      unfavourable for 50% of the patients; one patient had died. The psychosocial
      outcome was less favourable for 60%. Against the background of a neurotic
      structure, social and sexual disturbances were found although the patient's
      weight was often normal. Depressive symptoms and a "slimness ideal" were found
      among a large number of patients, just as much as the fear of gaining weight-
      which prove to be a reliable indicator for the continuation of an eating
      disorder. A multidimensional evaluation facilitates an assessment of the
      determinants of prognosis. Previous psychiatric treatment and low body weight
      were associated with an unfavourable, mention of problems/disturbances in the
      family environment with a good somatic outcome. Outpatient treatment indicates a
      favourable psychosocial outcome.

PMID- 9654982
TI  - [Prognosis of dangerousness in adolescent psychiatry expert assessment].
AB  - The clinical assessment and prediction of violent behavior are two of the most
      important, but also most difficult tasks for child and adolescent psychiatrists
      who work in the forensic psychiatric area. The purpose of this article is to give
      an overview about the most prominent aspects of this problem. Therefore the
      judicial, methodological and methodical basis of the prediction of dangerous
      behavior is discussed as well as different methods that are used to predict
      dangerous behavior. It is shown that "dangerousness" is in most cases the result
      of an interaction between the individual dispositions of a person and a violence
      prone situation. Furthermore it is put emphasis on the fact that many
      psychiatrists are not aware of their own cognitive processes that lead them to a
      conclusion concerning the dangerousness of a person and also do not use the bulk
      of the information that is available to them; so many studies showed that
      dangerousness is judged in the first line in the light of former delinquency and
      much less in the light of other anamnestic data or the actual behavior. Finally
      some proposals are made concerning the improvement of the quality of the clinical
      prediction of dangerousness.

PMID- 9654983
TI  - [Patient dismissal to promote progress: brief discharge as a possible method in
      inpatient psychotherapy of adolescent patients].
AB  - In dealing with aggressive juveniles in a setting it often is difficult to
      sustain the concept of therapy without risking the end of cooperation. A chance
      to save the ability to act on the therapist's side, offers the shorttime
      dismissal as a therapeutical measure. It works as a remedy in times of stationary
      crises' as well as a juncture with the juvenile's original system that is forced
      into the process of therapy closing links between the stationary ongoings and the
      dynamics of the familiar system outside.

PMID- 9654984
TI  - [The unwanted father: psychodynamic aspects of the relationship after separation
      and divorce].
AB  - Although the importance of the father for the development of the child is well
      known and although an increased presence of the father in the family system is
      often demanded, processes of active shutting out the father occur. The
      deterioration of relation between father and child is not seen as a result of
      pathological male personality, but rather as a result of family or couple system.
      The special situation for counsellors of such cases is discussed.

PMID- 9654985
TI  - [R.E.A.L. classification of non-Hodgkin lymphoma from the clinico-oncologic
      viewpoint].
AB  - In 1994 the International Lymphoma Study Group (ILSG) published the "Revised
      European-American Classification of Lymphoid Neoplasms" (R.E.A.L.
      Classification). Lymphomas were classified according to their presumed normal
      counterparts, to the extent possible. Within both T- and B-cell categories
      differentiation between lymphomas and/or leukemias of "precursor" or "peripheral"
      neoplasms are defined arising from antigen independend or antigen reactive cell
      proliferation. Lymphomas undoubtedly characterized by currently available
      morphologic, immunologic, and genetic technics represent "real" disease entities.
      Provisional categories include lymphomas that have been described in some detail,
      but without consensus within the ILSG. Proposed names are based predominantly on
      established usage. With respect to similar treatment approaches and difficulties
      of the ILSG members in subclassifying large cell lymphomas, centroblastic,
      immunoblastic and large cell anaplastic lymphomas of B-cell type were "lumped"
      together as large B-cell lymphomas. Within a prospective treatment trial overall
      survival was significantly better in centroblastic as compared to B-cell
      immunoblastic lymphoma diagnosed by optimal histomorphology according the
      criteria of the Kiel Classification. Thus the R.E.A.L. Classification fails to
      identify patients who may require other than standard treatment. Future studies
      will demonstrate whether subclassifying the proposed "peripheral" T-cell
      lymphomas, unspecified into T-zone lymphoma, lymphoepitheloid (Lennert's)
      lymphoma and pleomorphic, small, medium, and large cell lymphomas according the
      Kiel Classification is of clinicopathologic relevance. On the contrary the
      subtypes of chronic lymphocytic leukemia of T-cell type form two distinct
      entities within the R.E.A.L. Classification separating T-CLL/prolymphocytic
      leukemia from large granular lymphocyte leukemia of T- and NK-cell type. Within
      the R.E.A.L. Classification the lymphoplasmacytoid immunocytoma of the Kiel
      Classification will be subsumed together with the prognostically significantly
      better B-cell chronic lymphocytic leukemia. Opposite to the original intention of
      the ILSG two proposals are developed on clinical grouping of entities. Clinical
      indolent lymphoid neoplasms usually have "low grade" histologic appearances, with
      a predominance of small cells subsuming with the exception of the mantle cell
      lymphoma all of the low grade lymphomas of the Kiel classification. Aggressive
      lymphomas (intermediate risk) are defined as tumors whose survival if untreated
      is measured in months, highly or very aggressive lymphomas and/or leukemias will
      kill untreated patients within weeks. Unlike the Kiel Classification proposed
      categories subsume lymphomas irrespective of cytomorphology, thus grouping
      together potentially curable and uncurable diseases. Undoubtedly the R.E.A.L.
      Classification forms at present the best compilation of existing knowledge upon
      neoplasms of the immune system, enabling cooperation between clinicians and
      scientists all over the world. According to the ILSG this proposal should be
      considered a starting point for future periodic reevaluations.

PMID- 9654986
TI  - [Radiotherapy alone in early stages of low malignancy non-Hodgkin lymphomas].
AB  - About 25% of patients with low grade Non-Hodgkin's Lymphomas (NHL) of the B-cell
      type present in an early stage. They are candidates for radiotherapy alone.
      Thereby a complete remission can be achieved in the majority of stage I and II
      patients with centroblastic-centrocytic (cb-cc), centrocytic (cc) and immunocytic
      (ic) NHL--at least in cb-cc also a relapse-free survival of 50-60%.
      Standardization of the radiotherapeutic technique is essential to reduce the risk
      of recurrence. Retrospective analyses of radiotherapeutic studies from the
      literature are limited by the lack of homogenous irradiation techniques. Relapses
      occur inside as well outside of radiotherapy ports. It is the aim of current
      studies to optimize the radiotherapeutic approach with curative intent.

PMID- 9654987
TI  - [Systemic therapy of low malignancy non-Hodgkin lymphomas].
AB  - Substantial progress has been achieved in eludicating the molecular mechanisms of
      malignant transformation, in establishing therapeutic standards and in evaluating
      innovative treatment strategies in patients with low grade Non-Hodgkin's
      Lymphoma. Correlation of genetic aberrations and immunologic marker profiles to
      histopathological entities and the clinical course has lead to a new
      transatlantic lymphoma classification. Today, application of 6-8 courses of
      moderately intensive induction polychemotherapy induces partial or complete
      remissions in 80% of patients in stage III or IV. Longterm maintenance therapy
      with interferon alpha significantly prolongs progression free survival. Current
      multicenter trials evaluate the curative potential of high-dose chemotherapy with
      autologous stem cell transplantation. Recently, several new approaches including
      new cytostatic drugs, immunotherapy with monoclonal antibodies and gene therapy
      with antisense oligonucleotides have been developed and have achieved remissions
      in pretreated patients. In the future, intensification of chemotherapy and the
      new treatment options may offer the potential for cure in patients with low
      malignant Non-Hodgkins Lymphoma.

PMID- 9654988
TI  - [Treatment strategy of high malignancy non-Hodgkin lymphomas].
AB  - While radiotherapy is not justified as a single-modality approach in high-grade
      non-Hodgkin's lymphoma, standard therapy consists of chemotherapy with the CHOP
      regimen, which induces complete remissions in ca. 2/3 of the patients, with or
      without additional radiotherapy. Since the majority of these remissions do not
      last, dose escalations up to myeloablative ranges using hematopoietic stem cell
      support are being evaluated especially in young patients with bad risk factors.
      The trials of the German Non-Hodgkin's Lymphoma Consensus Trial group determine
      the value of a consolidating high-dose chemotherapy in young patients with high
      risk profile, while dose intensifications of the CHOP regimen by two-week
      regimens and/or the incorporation of etoposide are being evaluated in all other
      treatment groups.

PMID- 9654989
TI  - [Infectious spondylodiscitis--an important differential diagnosis in backache].
AB  - All cases of spondylodiscitis diagnosed in our hospital between January 93 and
      April 96 have been analysed retrospectively. With regard to potentially severe
      complications, spondylodiscitis is an important differential diagnosis of back
      pain. In our results 50% of the patients had a positive bacterial culture either
      from blood or tissue. No complication has been observed. The most relevant
      diagnostic procedures are: determination of CRP, magnetic resonance imaging and
      eventually computed tomography in combination with biopsy and blood cultures.
      Magnetic resonance imaging is a very sensitive method for early stage
      osteomyelitis. Antimicrobial therapy should be based on the result of culture and
      sensitivity tests. An antibiotic with good penetration into bone is preferred.

PMID- 9654990
TI  - [Overweight (obesity) from the psychiatric viewpoint and its relevance for
      general practice].
AB  - Obesity is of great importance for health and health economy. It often goes along
      with immense subjective and objective suffering. It has traditionally been a
      topic of general and internal medicine. This article summarizes results derived
      from recent psychiatric and psychotherapeutic approaches, that may also be of
      interest for the somatic physician as they contribute to the understanding and
      therapeutic management of the disease. Common definitions of obesity and
      epidemiologic data are presented. Traditional therapeutic approaches such as
      reducing diets often turned out to be insufficient. New knowledge, especially on
      ponderal and nutritional physiology (set point theory of body weight,
      investigations of dietary effects), studies about comorbidity with disturbed
      eating habits (particularly binge eating and bulimia) and about psychodynamics
      and life quality are expected to contribute to a better understanding of this
      phenomenon.

PMID- 9654991
TI  - [Intestinal paralysis in long-term diabetes mellitus].
AB  - A 74 year old patient with diabetes mellitus was hospitalized because of nausea,
      recurrent vomiting and increasing fatigue. Shortly before admittance the patient
      had diarrhea. He also reported a recent onset of aversion against meat
      consumption. Clinical investigation revealed a possible right-sided paraumbilical
      abdominal tumor, normal bowel sounds, a vascular bruit and a normal white blood
      count with increased band forms. During hospitalisation the general condition of
      the patient deteriorated rapidly with fever and increasing numbers of immature
      granulocytes. The patient finally died under the symptoms of a paralytic ileus
      with hypotonia and hypoglycemia. Autopsy revealed a fist-sized stenosing tumor in
      the cecum with the histology of a mainly well differentiated, cylindrocellular
      adenocarcinoma. As immediate cause of death a bilateral paracentral lung embolism
      with pulmonary edema was found, the latter probably as immediate consequence of
      preterminal heart failure.

PMID- 9654992
TI  - [Reversible dementia].
AB  - A 65 year old woman, referred for differential diagnosis of dementia, presented
      with cognitive and mnestic deficits. Typical signs and symptoms of hypothyroidism
      led to the diagnosis of severe autoimmune thyroiditis. After six months of
      treatment with thyroid hormone, dementia, myopathy and ataxia had disappeared.
      The neurologic and neuropsychologic manifestations of hypothyroidism are
      discussed. In dementia the diagnosis of secondary and reversible forms is of
      great importance with regard to prognosis and treatment. Hypothyroidism is known
      to be a common and treatable cause of pseudodementia. Early diagnosis and
      adequate treatment are important to prevent further permanent deterioration of
      cerebral function.

PMID- 9654993
TI  - [Recurrent bronchitis. Kartagener syndrome].

PMID- 9654994
TI  - [Chronic diarrhea and recurrent pulmonary infection. Variable
      hypogammaglobulinemia].

PMID- 9654995
TI  - [Fibromyalgia (generalized tendomyopathy) in expert assessment].

PMID- 9654996
TI  - [Molecular biology and multifunctional aspects of nm23/NDPK].

PMID- 9654997
TI  - [Stress response and molecular chaperones].

PMID- 9654998
TI  - [Double stranded RNA-activated protein kinase (PKR): the role in signal
      transduction and apoptosis].

PMID- 9654999
TI  - [Physiological functions of programmed cell death].

PMID- 9655000
TI  - [New aspect of neuron-specific proteins, synucleins and PNP 14, in
      neurodenerative diseases].

PMID- 9655001
TI  - [Autonomic regulation of melatonin synthesis through intrinsic glutaminergic
      systems in mammalian pineal glands].

PMID- 9655002
TI  - [Identification of organ-specific autoantigen in Sjogren's syndrome].

PMID- 9655003
TI  - [Osteoclastogenesis inhibitory factor (OCIF)].

PMID- 9655004
TI  - [Incidence of operations in Switzerland related to insurance status].
AB  - Several studies reported in the literature show that surgical procedures can be
      carried out for other than clinical indications. In Switzerland, no statistics on
      the "demography" of surgical procedures are available. But an earlier analysis of
      the "Swiss Health Survey 1992/93" gave first indications on differences in rates
      of surgical procedures (hysterectomy, appendectomy, tonsillectomy and operation
      of the hip and gallbladder) by sex, educational status and region. This study,
      based on the same datasource (N = 10792), reveals an additional link with the
      health insurance status. The prevalence of surgical procedures is higher in
      privately insured than in persons with only basic insurance, independent of age,
      sex and region. The highest rates of surgical procedures (except tonsillectomy)
      are found among privately insured persons with a low educational status. Among 25
      74 year old privately insured women, the lifetime-prevalence of a hysterectomy is
      30% with low and 13% with high educational status (p < .001). The corresponding
      prevalences of at least one of the mentioned surgical procedures (without
      tonsillectomy) are 49% versus 28% (p < .001). As these are lifetime-prevalences,
      these rates do not necessarily reflect the actual surgical procedures. However,
      an analysis of the period of operation for hysterectomy and for the gallbladder
      shows the same pattern as the mentioned lifetime-prevalences. Higher rates among
      privately insured are also a frequent finding in the international literature.
      These findings should stimulate patients to ask for a "second opinion".
      Furthermore, there is an urge for the implementation of general hospital
      statistics to verify such findings. In addition, the scientific consensus on the
      indication of several surgical procedures should be promoted on the way to more
      evidence-based-medicine.

PMID- 9655005
TI  - How to do it: aortic and mitral valve replacement through aortotomy.
AB  - Combined replacement of the aortic and mitral values is a relatively common
      operation. Occasionally it is feasible to replace the mitral value through the
      aortic root. This remarkable approach eliminates the need for a second atrial
      incision, and in reoperation it avoids extensive dissection and release of
      adhesions. Injury to the heart is minimized and the incidence of perioperative
      bleeding is reduced. The exposure is excellent and the operation is performed
      safely and expeditiously.

PMID- 9655006
TI  - [Surgical diagnosis and therapy in patients with mediastinal space-occupying
      lesions. A retrospective analysis of 223 intervention with special reference to
      long-term course].
AB  - The diagnostic and therapeutic approach in patients with mediastinal masses (MM)
      treated at our institute between 1983 and 1993 was retrospectively reviewed.
      METHODS AND MATERIAL: 193 patients with MM (105 males and 88 females, average age
      53, ranging from 16-81) underwent 223 interventions. Staging mediastinoscopies in
      lung cancer patients were ruled out. Long-term follow-up data were available in
      123 of 162 cases with neoplastic MM (average follow-up time 5.5 years). Of all
      223 surgical interventions 143 were diagnostic (53 parasternal mediastinotomies,
      78 mediastinoscopies and 8 thoracoscopies) and 80 therapeutic (46 sternotomies
      and 34 posterolateral and a second half). The analysed period was splitted up in
      a first half (1983-1987) and second half (1988-1993) to study an eventual trend
      in the management of MM. RESULTS: The most frequent diagnoses were: thymoma
      (21%), malignant lymphoma (18%) and mediastinal sarcoidosis (14%). 43% of the MM
      were localized in the anterior, 46% in the middle and 7% in the posterior
      mediastinum. Thoracic pain, cough and dyspnoea represented the most common
      symptoms, leading to an invasive diagnostic procedure. 25% of the patients had no
      symptoms. The mortality and morbidity rate of all interventions was 3.4% and
      18.7% respectively and concerned almost nerval injuries and postoperative
      respiratory failure. The percentage of direct tumor excisions increased from 21%
      during the first half of the period to 40% during the second half of the period,
      whereas diagnostic surgical interventions decreased from 57% to 44%. The
      percentage of total excisions after previous surgical biopsies decreased from 22%
      to 16%. In spite of the introduction of high resolution CT scan and MRI
      techniques during this time period no significant change in the use of
      presurgical diagnostic procedures was obvious. Fine needle biopsies and
      bronchoscopies were performed less frequent in the second half in comparison to
      the first half (11%, 7%, 29%, 13% respectively). From 123 patients with
      neoplastic disease data were available for long-term results. 35 had benign and
      83 malignant histologies, in five cases dignity was unclear. 54% of these
      patients were disease-free at follow-up time, 10% had local recurrency or distant
      metastasis and 37% died during the observed time period. CONCLUSIONS: Surgical
      biopsy seems to remain the most important investigation for a successful
      interdisciplinary approach to MM. Overall morbidity and mortality rate of
      mediastinal surgery might appear remarkable but has to be related to the favorous
      long-term results after different individual treatment modalities in patients
      with mediastinal masses.

PMID- 9655007
TI  - [Supragenicular bypass: venous in comparison with synthetic prosthesis (PTFE)].
AB  - In the time between 1984 and 1991 we have performed 136 infrainguinal arterial
      reconstructions to the supragenicular popliteal artery for lower extremity
      ischemia. We inserted in 98 cases the greater saphenous vein and in 38 cases a
      PTFE-prosthesis. Life-table primary patency rate at 5 years was 88% for the vein
      and 60% for the PTFE-grafts. Limb salvage results at 5 years were 92% and 76%. In
      our experience patency rates with PTFE are inferior compared with vein grafts
      even with distal anastomosis to the supragenicular popliteal artery. If we have
      to bypass we preferentially use the greater saphenous vein even in this position.
      "We do the best operation first".

PMID- 9655008
TI  - [Allo-transfusion saving measures in maxillofacial surgery].
AB  - In terms of a prospective clinical study between June 1994 and May 1996, in 204
      patients undergoing maxillo-facial surgeries with a expected blood loss of more
      than 500 ml a protocol of bloodsaving measures was followed. By means of an
      additional retrospective study, the consumption of homologous blood and the
      amount of bloodsaving measures between June 1990 and May 1994 was evaluated.
      Bloodsaving measures were consisting from acute normovolemic hemodilution,
      controlled moderate hypotension, cell saving, preoperative autologous blood
      donation, and administration of rh-erythropoetine. The methoda were applied
      isolated as well as in combination. Special concerns were given to a stable
      intraoperative homeostasis and to the acceptance of a low hematocrit
      perioperatively. Aim of the study was to investigate if, following the protocol,
      even in major maxillofacial procedures homologous blood transfusions almost
      completely can be avoided. Out of the 204 patients in the prospective study, only
      30 received homologous blood. For the period June 94 to May 96, the reduction of
      the number of patients receiving homologous blood in relation to the period June
      90 to May 94 was 83%. The results indicate that in the years 94 to 96 twice as
      much patients received bloodsaving measures. These led to a reduction of
      homologous blood consumption for 427 units in 1990 to 56 units 1996 (p < 0.001).
      If three measures, i.e. normovolemic hemodilution, cell saving, and hypotension
      were combined, the need of blood transfusion was at the minimum level. The
      effective reduction of homologous blood transfusion by consequent application of
      bloodsaving measures can with these data obviously be demonstrated.

PMID- 9655009
TI  - [A rare complication of permanent venous access: constriction, fracture and
      embolization of the catheter].
AB  - The pinch off syndrome due to squeezing of the implanted catheter is a rare
      complication of permanent venous access devices (0.1 to 1% of the cases). The
      cause is a mechanical catheter's compression in the costo-clavicular space, when
      implanted too medially in the subclavian vein. In case of lack of venous reflux
      or injection difficulties, sometimes complicated by local pain, a radiological
      control must be obtained to demonstrate signs of compression or beginning of
      fracture. Significant damage to the system is shown be extravasation of
      radioopaque contrast medium. The suspicion of catheter damage justifies early
      replacement of the system to avoid right heart or pulmonary artery embolism. The
      electron microscopic scanning tends to prove that the catheter's rupture is
      caused by a fatigue process.

PMID- 9655010
TI  - [Early postoperative nutrition after laparoscopic and open colorectal resection].
AB  - BACKGROUND: Discussions concerning postoperative nutrition were brought up again
      with laparoscopic colorectal surgery. We are looking whether there is any
      difference between open and minimal invasive procedures with respect to the start
      of oral intake. METHODS: In a prospective controlled trial 152 patients were
      analysed after laparoscopic (n = 85) or open (n = 67) colorectal resections. At
      the first postoperative day fluid intake was unlimited and from the second day
      regular food was permitted according to the patients desire. RESULTS: No
      influence on the beginning of nutrition was by age, diagnoses, type of operation
      nor their duration. Wound infection and specially cardiopulmonal decompensation
      prolonged lack of appetite, however, not a pneumonia. There was no increase of
      anastomotic leak rate. At day 4, a highly significant difference was found
      between laparoscopic and open surgery with 90% and 60% of patients having started
      regular nutrition (p < 0.001). CONCLUSION: Early postoperative oral nutrition
      does not increase complication rate. Patients after laparoscopic procedures start
      earlier eating compared with those after conventional surgery. We recommend early
      postoperative oral intake after both techniques according to the patients desire.

PMID- 9655011
TI  - [Submucous lipoma of the colon--report of 2 cases].
AB  - Gastrointestinal lipomas are benign but rare lesions, mainly located in the
      colon. Depending on their size they are responsible for obstructive bowel
      symptoms. Diagnostic tools are either the endoscopy or computer tomography. It is
      recommended to investigate the entire large bowel as other pathologies are often
      found. Any lipoma found should be removed. Two cases with symptomatic lipoma are
      presented. In both cases the lipoma was removed by open surgery.

PMID- 9655012
TI  - Some effects of representational friction, target size, and memory averaging on
      memory for vertically moving targets.
AB  - Observers viewed an animated ascending or descending target that varied in size
      and velocity across trials and appeared either (a) in isolation, (b) to slide
      along one side of a single larger stationary object, or (c) to slide between two
      larger stationary objects. Targets vanished without warning, and displacements
      (i.e., differences between actual and remembered final position) along the axis
      of motion and orthogonal axis were measured. Forward displacement (a) decreased
      with increases in implied friction, (b) increased with increases in target size
      for descending targets, and (c) decreased with increases in target size for
      ascending targets. When a larger stationary object was to one side of the target,
      orthogonal displacement was toward that object; when no object or objects on both
      sides were present, orthogonal displacement was near zero. Results are consistent
      with previous findings and speculation on the effects of representational
      friction, memory averaging, and target size on memory.

PMID- 9655013
TI  - The effect of spatial attention on memory scanning.
AB  - Participants responded to probe letters after sets of two, four, and six letters
      were memorized (Sternberg, 1966, 1969b). Spatial attention was controlled by
      central arrow cues and stimuli were presented in a clear or a visually degraded
      from. Overall RT was shorter for attended than for unattended locations, and
      shorter for clear than for degraded stimuli. Even though the function relating RT
      to memory-set size for stimuli in attended locations had a significantly smaller
      zero-intercept than the function for unattended locations, she slope was
      unchanged, which suggests that attention did not influence the memory-scanning
      stage. Visual quality interacted with attention, which suggests that they
      influenced the same stage of processing, presumably the early visual-encoding
      stage of processing.

PMID- 9655014
TI  - Display duration and stereoscopic depth discrimination.
AB  - We investigated the role of display duration in stereoscopic depth perception.
      The display consisted of a dynamic random-dot stereogram, with two disparity
      defined squares (1.9 degrees x 1.9 degrees), one on the left and one on the right
      of a central (Nonius) fixation stimulus. The sign of the disparity (crossed or
      uncrossed) was always the same for both squares, and the magnitude of disparity
      was 0.25 degree for one square and either 0.125 degree or 0.375 degree for the
      other square. Participants indicated which square appeared closer. The display
      duration was varied adaptively between 20 and 1000 ms until participants
      performed at 75% accuracy. Results confirmed large individual differences in the
      display duration required for stereoscopic depth perception. Approximately half
      of the 100 naive participants were able to perform the task at 20 ms, while the
      remaining participants required up to 1000 ms to perform at criterion. The
      present study shows that display duration is a critical variable in explaining
      wide differences in reported abilities of individuals to process stereoscopic
      depth information.

PMID- 9655015
TI  - Host mechanisms in the pathogenesis of periodontal disease.
AB  - Periodontal diseases present with a wide range of clinical variability and
      severity. Individual susceptibility seems to be of major importance in
      determining the manifestation and progression of the disease. A better
      understanding of the molecular mechanisms of action of the immune system is of
      paramount importance to our ability to prevent and treat occurrence and
      recurrence of periodontal diseases. Recent advances in immunobiology are very
      promising for the identification of special categories of patients at risk for
      periodontal breakdown. This review discusses the most recent studies in this
      field and the possible clinical applications of recent advances.

PMID- 9655016
TI  - Crevicular fluid biomarkers of oral bone loss.
AB  - The lack of predictive value in periodontal disease detection has stimulated
      intense research efforts in the development of diagnostic tests. Present
      methodology using periodontal probes or radiographs to determine disease
      susceptibility fails to allow an accurate periodontal risk assessment. The
      analysis of gingival crevicular fluid components offers great potential as a
      source of factors that may be involved in active periodontal bone loss. Over the
      past decade investigators have begun to identify several molecules associated
      with active periodontal tissue destruction. Recent advances in orthopedics and
      osteoporosis have provided new biochemical markers of bone resorption, including
      oral bone loss. The development of new diagnostic test strategies that target the
      analysis of bone-specific markers offers great promise to accurately assess
      active disease.

PMID- 9655018
TI  - Relationship of diabetes to periodontitis.
AB  - Although the relationship between diabetes and periodontal disease has been the
      subject of much debate, the consensus of recent studies is that diabetic patients
      have an increased risk of periodontal disease, particularly when metabolic
      control is poor. This paper reviews recently published studies in this area and
      concludes that not only is metabolic control a risk factor in disease
      susceptibility but that it may also influence the outcome of periodontal therapy.

PMID- 9655017
TI  - Association of the oral flora with important medical diseases.
AB  - Recently, there have been case-control and epidemiologic investigations that
      strongly associate poor dental health with cardiovascular disease, preterm low
      birth weight infants, and early death from any cause. In a 7-year prospective
      study, dental disease was a significant predictor of coronary events leading to
      death after controlling for known coronary disease risk factors. Missing teeth
      displaces smoking as a risk factor for ischemic heart disease in another study.
      Periodontal disease was seven times more likely to be associated with a preterm
      delivery of a low birth weight infant than mother's age, race, number of live
      births, and use of tobacco or alcohol. This review examines the role of
      asymptomatic bacteremia as possibly explaining these associations, focusing on
      the bacterial load on the teeth as mediated via oral hygiene.

PMID- 9655019
TI  - Systemic antibiotic therapy in severe periodontitis.
AB  - The main goal in the treatment of periodontitis is to control the subgingival
      infection. Systemic periodontal antibiotic therapy aims to reinforce mechanical
      debridement procedures and to support the host defense system in overcoming the
      infection that remains after conventional mechanical treatment. In particular,
      patients with early onset periodontitis and patients with refractory
      periodontitis may benefit from systemic antimicrobial therapy. Outside clinical
      parameters, the use of microbiologic information can assist in selecting the most
      optimal antibiotic regimen based on the presence and levels of selected
      periodontal pathogens.

PMID- 9655020
TI  - Periodontal pocket irrigation as adjunctive treatment.
AB  - The emphasis in periodontal treatment generally has shifted in recent years from
      periodontal surgery towards periodontal medicine. Because the major periodontal
      disease group is the chronic inflammatory group, and the major direct cause of
      chronic inflammation is dental plaque, much of the new research is directed at
      more ergonomic and economic means of plaque control that have the efficacy of
      traditional methods. As a result, the field of plaque chemotherapy is expanding
      concurrent with the modes of application of anti-plaque chemical agents to their
      interdental and subgingival sites of intended action. Since the rediscovery of
      subgingival irrigation some 15 years ago, the technique has been shown to provide
      an efficient means of subgingival application of anti-plaque agents, and it has
      also been used to apply anti-inflammatory compounds. It was never intended to
      stand alone. It was and is meant to be used as an adjunct to professional
      debridement, but one that simplifies home-care oral hygiene for the patient.
      This, indeed, is part of the aim of all chemical anti-plaque adjunctive therapy.
      It requires the use of appropriate anti-plaque agents in sufficient concentration
      and with sufficient periodicity to be clinically effective. It is only
      ineffective if dose or periodicity is inadequate, or if mechanical plaque control
      is unrealistically good--that is, unlikely to be maintained long term by the
      majority of patients. Subgingival irrigation enables the patient for the first
      time to deal with bursts of periodontitis activity when professional help is not
      readily available. Although irrigation per se may dilute plaque toxins, it is
      still clinically inadequate without a suitable chemical adjunct. Subgingival
      irrigation with a suitable antimicrobial agent currently constitutes an effective
      adjunct to the simplified oral hygiene regimen that does not require unrealistic
      levels of interdental or subgingival home-care cleaning by the patient.

PMID- 9655021
TI  - Nonsteroidal anti-inflammatory drugs as adjuncts in the management of periodontal
      diseases and peri-implantitis.
AB  - For the past three decades, prostaglandin E2 and other arachidonic acid
      metabolites have been recognized as important proinflammatory mediators in bone
      resorption and various forms of periodontal disease. Nonsteroidal anti
      inflammatory drugs are chemical compounds that selectively inhibit the synthesis
      of metabolites of the cyclooxygenase pathway, thereby blocking the production of
      prostaglandins, thromboxane, and prostacyclin. Inhibiting prostaglandin E2
      synthesis with nonsteroidal anti-inflammatory drugs has been unequivocally shown
      in both animal and human studies to be of primary therapeutic efficacy. Recent
      lines of nonsteroidal anti-inflammatory drugs research have focused on the
      development of daily topical administration forms such as gels, toothpastes, and
      rinses. Furthermore, new studies have implicated prostaglandin E2 in the peri
      implantitis process, opening the possibility to manage failing implants with
      topical nonsteroidal anti-inflammatory drug delivery systems.

PMID- 9655022
TI  - Prevention and treatment considerations in patients with drug-induced gingival
      enlargement.
AB  - Drug-induced gingival overgrowth is an iatrogenic disease caused by the use of
      phenytoin, cyclosporine, nifedipine, and other medications in the susceptible
      patient. The gingival overgrowth can be due to three causes: noninflammatory,
      hyperplastic reaction to the medication; chronic inflammatory hyperplasia; or a
      combined enlargement due to chronic inflammation and drug-induced hyperplasia.
      Drug-induced gingival enlargement can be minimized, but not prevented, by
      elimination of local irritants, meticulous oral hygiene, and regular periodontal
      recall. If gingival enlargement interferes with function, speech, esthetics, or
      oral hygiene, tissue reduction can be accomplished by gingivectomy or a flap
      procedure. Gingival enlargement may recur, especially in the patient with poor
      oral hygiene.

PMID- 9655023
TI  - Can surgery be justified for patients with periodontitis?
AB  - There is a debate concerning the role that surgical procedures should play in the
      treatment of inflammatory periodontal diseases. This review details some of the
      situations in which surgery can be of benefit. Benefits include obtaining
      shallower probing depths and therefore reducing the areas that are hospitable to
      pathogenic bacteria associated with disease. Also, removal of tooth-accumulated
      materials such as plaque and calculus in probing depths greater than 5 mm is more
      predictable with surgery. In some forms of aggressive periodontitis, elimination
      of potentially pathogenic bacteria is found more frequently with surgical
      procedures. Regeneration of lost bone and attachment apparatus are predictable
      only with surgery.

PMID- 9655024
TI  - Long-term prognosis following resectional and regenerative periodontal
      procedures.
AB  - The ultimate goal of both resective and regenerative periodontal procedures is
      the creation of soft- and hard-tissue architecture that is consistent with
      periodontal health. Osseous resective procedures predictably produce minimal
      clinical probing depth, but sacrifice periodontal support. An alternative method
      to treat anatomic defects not easily managed through resection is guided tissue
      regeneration (GTR). GTR provides clinicians with the opportunity to reverse the
      disease-related loss of periodontal attachment. However, at present, the outcomes
      of GTR procedures have not been shown to be predictable. Continued improvements
      in techniques and materials, and identification of patient-related factors
      significant to the success of the GTR procedures, should enhance the consistency
      of the clinical outcomes. An evidence-based approach to the use of both
      regenerative and resective therapies will enhance the clinical results achieved
      through these procedures.

PMID- 9655025
TI  - Clinical regeneration with guided tissue barriers.
AB  - This review of the current periodontal literature evaluates clinical regeneration
      with guided tissue barriers in infrabony defects and furcations. A meta-analysis
      was conducted by calculating weighted means with confidence intervals for each
      treatment group. Clinical improvement in infrabony defects was best for
      polylactic acid/polyglactin (PLA/PGA) barriers, with a mean pocket reduction of
      5.3 mm and a mean gain in clinical probing attachment level of 4.7 mm. For
      furcations, special attention was given to the frequency of either complete or
      partial (> or = 50%) furcation closure. Complete furcation closure was an
      infrequent result of guided tissue regeneration, occurring in only 7% to 19% of
      furcations treated with barriers. For the time period reported, the best clinical
      results in furcations and infrabony defects occurred with PLA/PGA-type barriers.
      However, there were no statistically significant differences among the various
      barriers in infrabony defects or furcations.

PMID- 9655026
TI  - Case selection and treatment considerations of guided tissue regeneration in deep
      intrabony defects.
AB  - Evidence reported in the period covered by this review, and here summarized with
      a meta-analysis, indicated that guided tissue regeneration (GTR) management of
      deep intrabony defects resulted in clinically significant and predictable gains
      in tooth support. Controlled randomized clinical trials demonstrated that GTR
      therapy was associated with significantly greater improvements in clinical
      attachment than access flap procedures alone. A series of recent investigations
      have also indicated that the magnitude and possibly the predictability of the
      expected outcomes are dependent upon a variety of patient, defect, and procedure
      associated factors. Substantial evidence has been provided that clinical
      improvements obtained with GTR can be maintained over time.

PMID- 9655027
TI  - Suture materials and techniques.
AB  - Surgical improvements in periodontics have been achieved because of advances in
      basic science, animal and clinical research, and the insight of outstanding
      clinicians. Industry continues to develop new surgical materials, improving the
      quality of sutures and needles and in turn, supporting advances in all surgical
      specialties. The purpose of this article is to review sutures and suturing by
      focusing on both materials and methods as they relate to the present practices of
      surgical periodontics and dental implants.

PMID- 9655028
TI  - An evidence-based approach to clinical practice guidelines in periodontics.
AB  - The use of clinical practice guidelines has received considerable attention in
      medicine and dentistry for improving clinical decision making and cost-effective
      care. Leaders in dentistry are increasingly calling for improved standardization
      of treatment through the development of clinical practice guidelines based on
      empiric clinical evidence. Guidelines have been shown to minimize treatment
      variability and ensure the quality and cost-effectiveness of care. Other
      potential applications include educating individuals or groups; development of
      quality indicators; improved allocation of resources such as insurance payment
      decisions; and reduced risk of liability for negligent care. Recently, a series
      of evidence-based clinical algorithms and practice guidelines were developed for
      regenerative periodontal treatment. Such guidelines have the potential to improve
      outcomes of periodontal care for providers, patients, and other interested
      parties. This review discusses the rationale for guideline development and the
      role of clinical practice guidelines in the area of periodontal decision making
      and provision of care.

PMID- 9655029
TI  - Do implant surfaces make a difference?
AB  - The synthetic biomaterials commonly used as an interface or surface for soft- and
      hard-tissue attachment and integration are commercially pure titanium, titanium
      alloy (usually Ti6A14V), and hydroxyapatite. This review attempts to address the
      following questions: Do the epithelium and connective tissue attach or adapt to
      these synthetic surfaces? Is there a seal or just a cuff in terms of the soft
      tissue interface? Is hydroxyapatite, commercially pure titanium, or Ti6A14V more
      predictable and retentive? Is one better than the other or are all the same? Is
      there an advantage of one surface over the other in terms of bone-to-implant
      contact or shear strength when stressed? How about bone density and fixture
      length; is one surface better than any other?

PMID- 9655030
TI  - Localized bone reconstruction as an adjunct to dental implant placement.
AB  - Advances in bone reconstructive techniques, including the potential of barrier
      membrane usage for osteogenesis, have increased the indications for implant
      placement. This review discusses the critical biologic and clinical criteria
      involved in achieving a predictable success with barrier membranes. Experimental
      and clinical findings have shown that the type of adjunctive grafting material
      used, healing time of the membrane site, type and size of bone defect, and
      membrane exposure all influence the end result. Small bony defects like implant
      fenestrations and intact extraction sites seem not to depend on the application
      of membranes to regenerate bone membranes. Large bone grafts used for ridge
      reconstruction purposes might benefit from membranes, because they reduce the
      inevitable resorption of bone grafts when used alone. New developments in
      material and tissue engineering have introduced the use of resorbable membranes,
      xenografts, and osteoinductive proteins, such as recombinant human bone
      morphogenic protein, that are likely to play a role in the treatment of localized
      ridge deficiencies.

PMID- 9655031
TI  - Prosthodontic and periodontal considerations for implant-supported dental
      restorations.
AB  - In the past two years, many reports concerning the outcome of treatment using
      dental implants have included more detailed data which allow insight into
      prosthodontic and periodontal considerations that affect success. It has become
      evident that unique biomechanical sequelae reflect the screw-joint character of
      the dental implant prosthesis. The relative stability of the screw joint and the
      biomechanical integrity of the components and prostheses themselves are new
      issues to contend with for restorative dentistry. The biologic sequelae of
      maintaining the implant-supported prostheses are revealed by bone maintenance and
      peri-implant mucosal health. The microbiologic similarity of tooth and implant
      associated plaque at inflamed sites suggests that infected teeth are sources of
      potentially pathogenic bacteria at implants. However, the pathogenesis of
      inflammatory disease at implants is not fully defined. The evaluation and
      prognostic criteria of peri-implant inflammation remain controversial topics. The
      present aggregate data indicate that the long-term evaluation of implant
      supported dental prosthesis must be performed with cautious optimism and
      attention to general biomechanical and biologic factors.

PMID- 9655032
TI  - Etiology, diagnosis, and treatment considerations in peri-implantitis.
AB  - Peri-implantitis is an inflammatory process affecting the tissues around an
      osseointegrated implant in function, resulting in loss of supporting bone. A
      review of the literature currently available leads to the conclusion that
      microorganisms play a major role in this disease. Gram-negative anaerobic
      bacteria, particularly fusobacteria, spirochetes, and black-pigmenting organisms
      such as Prevotella intermedia are often found in diseased sites. Several
      treatment modalities are presently being evaluated. Treatment aimed at a
      reduction of the anaerobic bacteria improves clinical conditions. Furthermore,
      case reports indicate a possibility for successful treatment with guided tissue
      regeneration procedures. However, to date histologic evidence of true
      reosseointegration has not been obtained. Incomplete surface decontamination
      seems to be the major obstacle for regrowth of bone onto previously exposed
      implants. It appears reasonable to attempt interception of destructive peri
      implantitis as early as possible and to stop progression by removal of the
      bacterial deposits.

PMID- 9655033
TI  - Breath malodor.
AB  - Breath odor research has recently received increasing attention from
      periodontologists. Because a large portion of the adult population suffers from
      gingivitis and eventually periodontitis, the etiologic factor in all cases at
      risk must be considered. The first patient visit should, therefore,
      systematically include examination of the paranasal cavities and throat to avoid
      unnecessary time loss and frustration. Metabolic diseases and imaginary malodor
      should also be considered. Not only the mere presence of a chairside volatile
      sulfide monitor but also of that of an ear, nose, and throat specialist and
      eventually a psychiatrist or psychologist who determines whether a breath odor
      clinic merits its denomination. Volatile sulfur components are an important cause
      of breath malodor but they are not the sole cause. This explains why organoleptic
      and gas chromatographic diagnosis scores better than a portable sulfide monitor.
      Other than etiologic therapy, masking can be achieved for a number of hours by
      toothpastes containing a combination of triclosan and zinc chloride.

PMID- 9655034
TI  - Treatment of orofacial pain and temporomandibular disorders.
AB  - The treatment of orofacial pain and temporomandibular disorders has evolved into
      a multidisciplinary approach using various modes of treatment and other medical
      specialties as indicated. An excellent four-part, self-directed learning module
      written by Goddard [1.], King [2.], Williams [3.], and Dean [4.] provides an
      overview of accepted pain rehabilitation that includes basic science, chronic
      pain, myofascial pain, cancer pain, and therapeutic options. An outstanding
      review of the anatomy of the human temporomandibular joint is presented by Piette
      [5.]. This brief review provides an update for the practitioner concerning recent
      advances and research in the area of clinical treatment.

PMID- 9655035
TI  - Supportive care of the periodontal patient.
AB  - The ultimate goal of supportive periodontal care is to maintain health of the
      dental and oral soft tissues. It represents a preventive measure for individuals
      who have never experienced periodontal problems. On the other hand, supportive
      care is a continuation of therapy for the treated periodontal patient, once
      health has been reestablished. It aims at optimizing the results of therapy and
      prevent further destruction following active treatment. Attempts are being made
      to individualize and tailor supportive periodontal care according to the
      patient's profile and needs. Recent trends also show increased use of
      antimicrobials as adjuncts to mechanical procedures for controlling the etiologic
      agents.

PMID- 9655036
TI  - Field cancerisation in the head and neck.

PMID- 9655037
TI  - Increased expression of epidermal growth factor receptor in normal epithelium
      adjacent to head and neck carcinomas independent of tobacco and alcohol abuse.
AB  - OBJECTIVE: In this study we examined if expression of the epidermal growth factor
      receptor (EGFR) in normal epithelium adjacent to head and neck squamous cell
      carcinomas (HNSCC) is increased and if this increase is due to the use of tobacco
      and alcohol. MATERIALS AND METHODS: Cut sections of formalin-fixed and paraffin
      embedded material of histologically normal epithelium adjacent to HNSCC from 25
      patients who smoke excessively and abuse alcohol, and 17 HNSCC patients who do
      not abuse tobacco and alcohol were compared with cut sections of normal
      epithelium from 27 control individuals. The sections were immunohistochemically
      stained for the EGFR. RESULTS: We show an elevation of the expression of the EGFR
      in patients who smoke and drink excessively, that could also be ascertained, to a
      lesser extent, in patients that do not have a history of smoking or drinking (P =
      0.08). We also find that the closer the epithelium lies to the HNSCC the higher
      the expression of the EGFR is. CONCLUSIONS: Expression of the EGFR is increased
      in tumour-adjacent epithelium and this is not only due to the use of tobacco
      and/or alcohol. We suggest that paracrine effects of the HNSCC and migration of
      tumour cells may also play a role in this increased expression.

PMID- 9655038
TI  - Bromodeoxyuridine incorporation and Ki 67 expression in oral hairy leukoplakia.
AB  - OBJECTIVES: Oral hairy leukoplakia (HL) is an acanthotic, hyperparakeratotic
      lesion characterised by the presence of a replicative Epstein-Barr virus (EBV)
      infection in the superficial and adjoining layers of the epithelium. EBV or its
      gene products are capable of modifying epithelial differentiation. The aim of
      this study was to establish whether the presence of EBV was associated with an
      alteration in cell turnover by assessing bromodeoxyuridine (BrdU) incorporation
      and Ki 67 expression in lesional tissue and control mucosa. METHODS: Biopsies of
      HL together with age, site and sex matched controls (n = 7 and 8 respectively)
      were incubated in 200 microM BrdU in vitro, fixed in methacarn and processed to
      paraffin wax. Following acid hydrolysis, incorporated BrdU and Ki 67 were
      identified in serial 5 microns sections using a three-stage immunoperoxidase
      technique and cell density expressed as the number of positive cells per mm
      basement membrane length. RESULTS: Overall, there was no difference in the number
      of BrdU positive cells per mm basement membrane length between control and HL
      tissue. However, within HL alone, the presence of focal EBV replication was
      associated with a significant reduction in the number of basal cells
      incorporating BrdU compared to adjacent EBV free areas (P < 0.05). There was no
      significant difference between Ki 67 positive cells in control and HL tissue and
      no evidence of a reduction of Ki 67 positive cells in areas associated with EBV
      replication. CONCLUSIONS: These results suggest that there is no evidence of a
      generalised alteration of the proliferative capacity of basal cells in HL,
      although the focal reduction in BrdU incorporation may reflect subtle changes on
      cell turnover by EBV infection.

PMID- 9655039
TI  - Association of cutaneous and oral diseases in HIV-infected men.
AB  - OBJECTIVES: Mucocutaneous diseases are common in patients infected with human
      immunodeficiency virus (HIV). To identify cutaneous diseases for which HIV
      infected people are at high risk, we sought those that are strongly associated
      with specific HIV-related oral lesions and with progression of HIV disease.
      DESIGN: A cross-sectional study of HIV-positive outpatients referred to a
      university stomatology clinic for diagnosis and treatment of oral diseases. Each
      subject underwent both complete oral and cutaneous examinations. RESULTS: Among
      55 men, with a median age of 41 years and a median CD4 cell count of
      125/microliter (range 0-950/microliter), 93% had active oral diseases or
      conditions, including candidiasis, hairy leukoplakia, ulcers, Kaposi's sarcoma
      (KS), and xerostomia, and 95% had skin conditions, including onychomycosis,
      dermatophytosis, seborrheic dermatitis, KS, folliculitis, xerosis, and molluscum
      contagiosum. Seborrheic dermatitis, xerosis, skin KS, and molluscum contagiosum
      were associated with oral HIV-sentinel lesions (oral candidiasis, hairy
      leukoplakia, and KS), with low CD4 cell counts, and with AIDS. CONCLUSION: Our
      results suggest that xerosis and seborrheic dermatitis may be early harbingers of
      HIV disease progression. Their roles as predictors warrant further study, based
      on their associations with low CD4 cell counts and AIDS and strong co-prevalence
      with one of the most common HIV-related oral lesions, oral candidiasis.

PMID- 9655040
TI  - Resource implications for oral care of patients with HIV.
AB  - OBJECTIVES: The aim was to investigate the attitudes of people with HIV infection
      towards their own dental care provision and the possible implications for future
      resource allocation. DESIGN: Sixty-nine HIV positive subjects attending support
      groups in London were interviewed. Past and current dental visiting behaviour,
      problems encountered in obtaining dental care and preferred site of delivery for
      dental care were investigated. RESULTS: Showed that a majority (74%) changed
      dentist or stopped attending following diagnosis with HIV, either due to fear of
      or actual refusal of treatment, a desire to attend a more sympathetic dentist or
      to attend a specialist clinic. Forty-five per cent withheld information about
      their status. Subjects expressed a desire to receive regular dental care and had
      definite preferences as to the site of delivery, 45% preferring general practice,
      48% specialist clinics. CONCLUSIONS: Future resource allocation should be used
      for continued support and education of general dental practitioners willing to
      treat HIV positive patients, and for accessible specialist referral centres.
      Hospital clinics could also provide regular routine care, especially in areas of
      large HIV populations. An improved awareness of and access to community dental
      clinics appears to be needed, with efforts focused on achieving an informed and
      educated patient population through education programmes.

PMID- 9655041
TI  - The frequency of fungal infection in biopsies of oral mucosal lesions.
AB  - OBJECTIVE: To determine the frequency of fungal infection in biopsies of oral
      mucosal lesions. MATERIALS AND METHODS: Histopathology reports issued between
      1991-1995 inclusive were reviewed. During this period, a single section of each
      mucosal biopsy had been stained using the periodic acid-Schiff (PAS) technique.
      RESULTS: A total of 223 (4.7%) biopsies contained PAS-positive fungi: 191
      individuals were affected, 124 (64.9%) of whom were male. There was a significant
      (P < 0.01) positive association of fungal infection with moderate and severe
      epithelial dysplasia, median rhomboid glossitis and squamous papillomas. Where a
      subsequent biopsy was available, 21.9% dysplasias which were infected with fungi
      worsened in histological severity, as compared with 7.6% of dysplasias which were
      not infected at any stage. There was a significant negative association of fungal
      infection with benign fibrous overgrowths (P < 0.01), benign hyperkeratoses,
      lichenoid reactions and pyogenic granulomas (P < 0.05). The difference in
      frequency of infection between the tongue and other sites was also significantly
      higher (P < 0.01). CONCLUSIONS: There is a statistically significant association
      between histologically-determined fungal infection and epithelial dysplasia, and
      we recommend that a PAS stain be performed whenever oral epithelial dysplasia is
      diagnosed, especially in male patients. On histological confirmation of
      dysplasia, anti-fungal therapy should be considered in the management of these
      lesions.

PMID- 9655042
TI  - Age, gender, dentures and oral mucosal disorders.
AB  - The numbers of participants over 75 years of age in previous studies of oral
      health have not been sufficient to permit a full investigation of the influence
      of age on the mouth. In this study a disproportionate stratified random sample of
      255 independent elders was selected from a list of urban voters to provide
      similar numbers of men and women in three age groups. The subjects were
      interviewed and examined, and nearly half of them had mucosal disorders. There
      was a significant (P < 0.05) association between mucosal lesions and the use of
      dentures and tobacco, whereas stomatitis, denture-related hyperplasia and angular
      cheilitis in particular were associated significantly with men and with the use
      of defective dentures. Logistic regression revealed that neither age alone nor
      the quality of dentures predispose to mucosal lesions, but that the odds of
      finding stomatitis, denture-related hyperplasia and angular cheilitis in
      particular increased about three-fold in denture-users, and almost doubled in
      men.

PMID- 9655043
TI  - Prevalence of oral lichen planus in diabetes mellitus according to the type of
      diabetes.
AB  - OBJECTIVE: The purpose of the present study was to determine the prevalence of
      oral lichen planus (OLP) in a population of patients with diabetes mellitus (DM)
      as compared with a control population. DESIGN: A clinicopathologic study.
      SUBJECTS AND METHODS: One hundred and thirty-nine patients with type I DM, 353
      patients with type II DM and 274 controls were examined for clinical evidence of
      OLP. The clinical evidence of OLP in the diabetic and control patients was
      confirmed by histopathological examination. RESULTS: The prevalence of OLP in
      type I diabetic patients was 5.76%, in type II 2.83%, and 1.82% in the controls.
      The prevalence of OLP was significantly higher in patients with type I DM and
      slightly higher in patients with type II DM in comparison to the prevalence in
      the control sample. CONCLUSIONS: The above findings and the fact that type I
      diabetes and OLP are characterized by autoimmune phenomena and T cell immune
      responses respectively, suggest that the immune system may play a critical role
      in the appearance of OLP in patients with type I DM.

PMID- 9655044
TI  - Surgical emphysema: an unusual complication of punch biopsy.
AB  - Punch biopsies are frequently used in the diagnosis of oral disease and are
      associated with few complications. We report a case of surgical emphysema
      following this procedure.

PMID- 9655045
TI  - The role of IL-6 in the pathogenesis of periodontal disease.
AB  - The mechanisms underlying periodontal disease involve complex interactions
      between bacterial products, host cells and locally produced, biologically active
      factors. The umbrella term cytokine has been used to include a variety of such
      factors, including the interleukin family. The role of one cytokine, IL-1 beta,
      in periodontal disease pathogenesis has been widely reported. More recent studies
      have focused on a potential role for IL-6 in driving the destructive processes.
      Most of these reports have suggested a pro-inflammatory role for IL-6 alongside
      IL-1 and TNF-alpha. This manuscript reviews the biological functions of IL-6,
      specifically related to tissue destruction at the periodontal site. We would
      suggest that the activity of IL-6 in periodontal disease differs from IL-1 and
      TNF-alpha, and may, in part, play a protective role.

PMID- 9655046
TI  - EU Working Group on Tobacco and Oral Health Consensus Meeting. Copenhagen, 23-26
      October 1997. Abstracts.

PMID- 9655047
TI  - Utilization of ceromer inlays/onlays for replacement of amalgam restorations.
AB  - Fiber-reinforced Ceromer technology has been recommended for a variety of
      restorations, including inlays/onlays, crowns and bridges, and direct
      restorations. Ideal restorative dental materials must exhibit adequate physical
      properties and fit, as well as ease and predictability of fabrication and repair.
      The Ceromer restorative material combines the positive attributes of indirect
      composite restorations, feldspathic ceramics, and cast-gold restorations. This
      article reviews the material properties and aesthetic characteristics inherent to
      Ceromers, as well as the appropriate preparation and adhesive techniques for
      inlay/onlay restorations.

PMID- 9655048
TI  - Bioaesthetic ceromer restorations for the replacement of existing posterior
      amalgam restorations.

PMID- 9655049
TI  - Aesthetic guidelines for second-generation indirect inlay and onlay composite
      restorations.
AB  - Recent innovations in indirect composite technology and adhesive bonding
      procedures have resulted in the development of advanced materials particularly
      suited for inlay and onlay restorations. Microhybrid composite resins are
      characterized by a filler/matrix ratio that is significantly greater than that of
      earlier materials. This article reviews the physical properties and clinical
      application of these "second-generation" composite resins, with emphasis on a
      system that utilizes a heat-curing process in conjunction with nitrogen pressure
      to fabricate a material with improved mechanical and aesthetic properties.

PMID- 9655050
TI  - Soft tissue punch technique for aesthetic implant dentistry.

PMID- 9655054
TI  - Adhesive composite inlays for the restoration of cracked posterior teeth
      associated with a tongue bar.
AB  - While body piercing has become fashionable in contemporary society, numerous
      health risks are directly related to this trend. Tongue piercing in particular
      presents several concomitant complications for the attending clinician, including
      the possibility of soft tissue infection or damage to the natural dentition or
      existing restorations. Clinicians must be proficient in the selection of the
      proper materials and techniques utilized to treat affected patients. This article
      details a comprehensive clinical protocol for the use of adhesive composite inlay
      restorations for cracked posterior teeth.

PMID- 9655055
TI  - Pain as a motivator (Part II).

PMID- 9655056
TI  - Looks can deceive.

PMID- 9655057
TI  - Adhesive crowns and fixed partial dentures fabricated of ceromer/FRC: clinical
      and laboratory procedures.
AB  - Ceramic optimized polymer and fiber-reinforced composite materials represent a
      significant development in prosthetic dentistry. When utilized in conjunction
      with adhesive luting techniques, exceptionally conservative crown and bridge
      restorations may be achieved. This article discusses utilization of these
      materials in inlay and onlay restorations, as well as clinical and laboratory
      procedures for fabrication, preparation, and seating of adhesive crown and bridge
      restorations. The initial results of restorations utilizing these innovative
      materials are presented.

PMID- 9655058
TI  - Restoration of a posterior tooth utilizing a single-pontic FRC fixed partial
      denture.

PMID- 9655059
TI  - Root resorption of dental and traumatic origin: classification based on etiology.
AB  - While root resorption is a relatively common complication of dental trauma,
      classifications of root resorption are inconsistent and confusing. All
      pathological root resorption of dental origin is inflammatory in nature. For root
      resorption to occur, the protective superficial layer must be (internally or
      externally) damaged or changed and an inflammatory stimulator must be present.
      This article attempts to classify root resorption on the basis of etiology, i.e.,
      the cause of the protective layer loss and the cause of the inflammatory
      response, to facilitate more efficient treatment.

PMID- 9655060
TI  - Adhesive dentistry: what's new beyond aesthetics.

PMID- 9655061
TI  - Application of composite resin for single-appointment anterior and posterior
      diastema closure.
AB  - Due to aesthetic and periodontal factors, patients often seek treatment to close
      diastemata. This condition may be eliminated by either direct or indirect
      techniques. Indirect techniques generally require multiple visits to facilitate
      the placement of laminate, crown, or bridge restorations, and involve significant
      financial expense. Direct techniques can be economical and successful, although
      they present unique challenges in the achievement of satisfactory proximal
      contacts and contours. This article describes three clinical techniques that may
      be employed to treat anterior and posterior diastemata in a single appointment.

PMID- 9655062
TI  - Education and communication: now more than ever.

PMID- 9655063
TI  - Principles of proximal cavity preparation and finishing with ultrasonic diamond
      tips.
AB  - Conventional treatment of proximal cavities can result in significant damage to
      the adjacent dentition. This paper describes a recently developed technique of
      proximal cavity preparation and finishing by use of selectively diamond-coated,
      ultrasonically driven instruments. By using these instruments for composite,
      compomer, ceramic, amalgam, and even gold restorations, the inadvertent damage to
      neighboring teeth is completely avoided. This article demonstrates the effective
      utilization of the diamond-tipped ultrasonic instruments for the preparation of
      primary lesions and the replacement of existing restorations.

PMID- 9655064
TI  - Mulling microdentistry.

PMID- 9655065
TI  - In vitro and in vivo adhesion in operative dentistry: a review and evaluation.
AB  - Dentin and enamel bonding agents (DBAs) were introduced in the early 1980s to
      prevent volumetric shrinkage of composite resins used as restorative materials,
      to ensure dentin and enamel marginal sealing, and to prevent the dislocation of
      restorations during occlusal loading of the tooth. Today, DBAs play an important
      role in cosmetic and aesthetic dentistry and have radically altered the
      performance of operative dentistry. This article identifies the mechanical and
      physical properties of DBAs that facilitate the bonding of enamel, dentin, and
      various other restorations.

PMID- 9655066
TI  - Pain management. Pain as a motivator (Part I).

PMID- 9655069
TI  - Flowable composites: properties and applications.

PMID- 9655070
TI  - Preparation and restoration of small interproximal carious lesions with sonic
      instruments.
AB  - Partially diamond-coated oscillating preparation instruments are particularly
      suited for cutting minute interproximal cavities. This review presents an
      oscillating preparation system with newly designed working tips for cutting and
      finishing proximal microcavities. Analysis of the margins of various cavity
      designs prepared with this instrumentation exhibited outlines that were
      essentially free of defects. The method and instruments presented allow cutting
      of minute first intervention cavities of interproximal lesions with defect
      related extension. Enhanced margins can be attained without concomitant damage to
      adjacent tooth surfaces.

PMID- 9655071
TI  - Restoration of the maxillary arch utilizing a composite resin buildup and a fiber
      framework.

PMID- 9655072
TI  - Treatment options for the radicular lingual groove: a review and discussion.
AB  - The radicular lingual groove (RLG) is a developmental anomaly in which an
      infolding of the inner enamel epithelium and Hertwig's epithelial root sheath
      create a groove that passes from the cingulum of maxillary incisors apically onto
      the root. Radicular lingual grooves can create periodontal and pulpal pathology,
      but they may be difficult to identify as an etiological factor. This article
      identifies the diagnostic and treatment modalities for the various forms of RLGs
      and describes the prognosis that can be anticipated with each treatment modality.

PMID- 9655073
TI  - The cost of higher education.

PMID- 9655074
TI  - Cost of dental education and student debt.

PMID- 9655075
TI  - A primer on financial aid.
AB  - It is apparent that financial aid is a complicated, ever-changing business. The
      information provided in this article is only the tip of the financial aid
      iceberg. As student debt levels continue to increase, I encourage deans to work
      cooperatively with their financial aid officers. Invite your financial aid
      officers to participate in orientation and other pre- and post-admission
      activities, help facilitate effective entrance and exist interviews, and
      encourage financial aid officers to meet and work with your students on a
      frequent basis. I also strongly encourage you to support their participation in
      national meetings such as the Professional Development Conference (PDC) for
      Health Professionals (which AADS cosponsors with the AAMC) and the National
      Association of Student Financial Aid Officers (NASFAA). Participation in annual
      conferences is an important way for financial aid officers to network with other
      officers and to learn about important new legislation.

PMID- 9655076
TI  - Summary of federally funded loan repayment programs.

PMID- 9655077
TI  - State-supported forgiveness programs.

PMID- 9655078
TI  - Implications of changes in funding for graduate medical education.

PMID- 9655079
TI  - The future of U.S. health care and its effect on health care education.

PMID- 9655080
TI  - Evaluation of a computer-assisted test engine in oral and maxillofacial
      radiography.

PMID- 9655081
TI  - The central response to ovarian carcinoma simulates the response to sepsis.
AB  - BACKGROUND: Animal models of stress and sepsis demonstrate increased hypophyseal
      gene expression of the transcription factor c-fos and the cytokines interleukin-1
      and interleukin-6. Chronic central nervous system exposure to interleukin-1
      results in hypermetabolism, accelerated nitrogen loss, anorexia, and cachexia. We
      test the hypothesis that the host response to ovarian carcinoma recapitulates the
      host response to sepsis regarding the elaboration of the transcription factors
      and cytokines in the central nervous system, liver, and lung. MATERIALS AND
      METHODS: Nude mice were seeded intraperitoneally with either ovarian carcinoma
      (MA-148) or vehicle. The animal subjects were observed for 5 weeks and sacrificed
      for brain, pituitary, lung, and liver mRNA. We studied the mRNA accumulation of
      the transcription factors c-fos, c-jun, and C/EBP alpha and the cytokines
      interleukin-1 and interleukin-6 using reverse-transcriptase polymerase chain
      reaction. RESULTS: Compared with the control, ovarian carcinoma in the mouse
      model resulted in the following: (1) Pituitary c-fos and c-jun mRNA increased 3
      fold (P = 0.012) and 6-fold (P < 0.001), respectively; (2) pituitary IL-1 and IL
      6 mRNA increased 4-fold (P < 0.001) and 8-fold (P = 0.037), respectively; (3)
      liver c-fos mRNA increased > 8-fold (P < 0.001); and (4) lung C/EBP alpha mRNA
      decreased greater than 10-fold (P < 0.001). CONCLUSIONS: We conclude that the
      host response to ovarian carcinoma in this animal model recapitulates many
      aspects of the host response to bacterial sepsis especially concerning pituitary
      gene expression. These data suggest that, as in sepsis, a hypothalamic
      hypophyseal-mediated cytokine response in ovarian carcinoma may result in
      hypermetabolism, accelerated nitrogen loss, anorexia, and cachexia.

PMID- 9655082
TI  - Clinical experience with cryosurgery for advanced hepatobiliary tumors.
AB  - INTRODUCTION: There have been reports that suggest cryosurgical techniques may be
      a useful adjunct to surgical resection or even a viable alternative treatment for
      hepatobiliary malignancies. Our objective was to evaluate the clinical results
      following cryoablation in conjunction with surgical resection for advanced
      hepatic tumors. MATERIALS AND METHODS: Thirty-two consecutive procedures in 31
      patients with advanced liver tumors treated with cryosurgical ablation were
      evaluated. Cryosurgery was applied: (1) to achieve a > 1-cm tumor-free margin
      when standard surgical margins were close (2) with or without standard surgical
      resection to manage multiple tumors (3) with hepatic arterial portocath placement
      to increase tumor response. Cryoablation was applied to 47 of 105 lesions-
      independently in 4 patients and in combination with hepatic resection in 28
      procedures. RESULTS: Cryoablation was used in 11 procedures because of close
      surgical margins. In 21 operations cryosurgery was used for primary ablation. In
      17 of these 21 patients both cryosurgery and resection were used for different
      lesions; in 4 cryosurgery alone was used. Transient changes in hepatic enzymes,
      PT, PTT, and platelets were at maximum on Postoperative Days 1-3. Surgical
      mortality and morbidity rates were 6 and 60%, respectively. Coagulation
      abnormalities were common: at least 30% reduction in platelets occurred in all
      patients and greater than a 50% reduction occurred in 19 of 32 (59%). Twenty
      patients had a PT > 15 s and 6 of these 20 also had a platelet count < 50,000.
      Associated complications included one wound hematoma, two GI hemorrhages, one
      intracranial hemorrhage, and one hepatic hemorrhage from the cryosurgical site.
      The actuarial patient survivals were 90, 59, 33, and 22% at 6, 12, 24, and 36
      months, respectively. CONCLUSIONS: This report helps define the risks and results
      of cryosurgical ablation as a complement to surgical resection for advanced
      hepatobiliary tumors. Management of lesions contiguous to major blood vessels may
      include either the Pringle maneuver or total vascular isolation. Since these
      procedures can have significant morbidity, we urge cautious application of
      cryosurgery for advanced hepatobiliary tumors in selected otherwise unresectable
      patients.

PMID- 9655083
TI  - Ischemia/reperfusion injury of the pancreas: a new animal model.
AB  - BACKGROUND: Ischemia/reperfusion is thought to play an important role in the
      development of postimplantation pancreatitis after pancreas transplantation and
      also in the transition of edematous pancreatitis into necrotizing pancreatitis.
      Previous studies have suggested that impairment of microcirculation and hence
      tissue oxygenation and energy metabolism may be critical steps in this process.
      MATERIALS AND METHODS: In landrace pigs vascular isolation of the pancreatic tail
      was performed. Morphological alterations, tissue oxygenation, and energy
      metabolism were assessed in response to 3 h of global warm ischemia and the
      following reperfusion. RESULTS: A rapid onset of morphological alterations
      immediately after reperfusion was noted. Oxygen consumption and ATP levels were
      markedly decreased, and tissue oxygenation was severely impaired especially
      during the first hour after reperfusion. ATP tissue levels and oxygen consumption
      10 min after reperfusion correlated significantly with the morphological changes
      at the end of the experiment. CONCLUSION: These findings can be explained by a
      failure of nutritive capillary perfusion and concomitant shunt perfusion.
      Therefore an impaired microcirculation rather than an impaired oxygen utilization
      shortly after reperfusion is of major relevance in the development of the
      ischemia/reperfusion injury of the pancreas.

PMID- 9655084
TI  - Protection by cyclosporine A against normothermic liver ischemia-reperfusion in
      pigs.
AB  - BACKGROUND: Cyclosporine A (CYA) is primarily utilized as an immunosuppressant,
      but its mechanisms of action (including decreased neutrophilic free radical
      production and stabilization of mitochondrial and lysosomal membranes) may have
      beneficial effects in ischemia and reperfusion (IR) injury. This study was
      undertaken to examine the effect of CYA pretreatment on porcine liver
      histopathologic changes and enzymatic release caused by ischemia and reperfusion.
      MATERIALS AND METHODS: CYA was administered orally for 4 days prior to surgery in
      two doses (10 or 20 mg/kg) while controls received only the control vehicle. Pigs
      were then exposed to 4 h of hepatic ischemia followed by 2 h of reperfusion.
      RESULTS: Significant decreases in AST levels compared to controls were seen in
      high dose CYA pigs at the end of ischemia and at 30-min intervals during the
      reperfusion period. Controls exhibited necrotic hepatocytes and severe
      inflammatory cell infiltration, while high dose CYA animals demonstrated mild
      inflammatory cell infiltrates. Controls had decreased survival--20% did not
      survive reperfusion. CONCLUSIONS: This study indicates that CYA may be useful in
      decreasing initial damage resulting from warm hepatic IR injury.

PMID- 9655085
TI  - Nitric oxide inhibits peroxide-mediated endothelial toxicity.
AB  - BACKGROUND: Oxidant molecules and nitric oxide (NO) have each been implicated as
      mediators of endothelial cell damage, but the biologic effect of these molecules
      acting in concert is incompletely understood. MATERIALS AND METHODS: We studied
      the effects of an NO donor, S-nitroso-acetyl-D,L-penicillamine (SNAP), in
      combination with the peroxidants tert-butyl hydroperoxide (TBH) and hydrogen
      peroxide (H2O2) on rabbit aortic endothelial cells in culture. Cell viability was
      assessed using Alamar blue, a nontoxic dye indicator of cell metabolism. Lipid
      peroxidation was assessed using a chemiluminescent single-photon counting
      technique. RESULTS: After 90 min exposure to test reagents, there was
      concentration-dependent cytotoxicity for both TBH and H2O2. Peroxidant-induced
      cytotoxicity was significantly ameliorated by SNAP (10(-4)-10(-3)M). N
      Acetylpenicillamine and NO-depleted SNAP failed to demonstrate a cytoprotective
      effect against peroxidant cellular injury, thus implicating NO as the agent
      responsible for the protective effect. SNAP reduced lipid peroxidation caused by
      10(-3) M TBH in a dose-dependent manner. Preincubation of cells with SNAP before
      exposure to peroxidants alone had no effect on toxicity. CONCLUSIONS: NO is
      cytoprotective to the endothelium in the presence of peroxidants through a
      reduction of lipid peroxidation.

PMID- 9655086
TI  - Myosin heavy chain expression in skeletal muscle autografts under neural or
      aneural conditions.
AB  - BACKGROUND: Our purpose was to investigate (1) the heterogeneity of satellite
      cells derived from adult fast-twitch and slow-twitch skeletal muscles, (2) the
      influence of innervation on muscle regeneration, and (3) the differences between
      developmental myoblasts and satellite cells with regard to myosin heavy chain
      (MHC) expression. MATERIALS AND METHODS: Autografts under neural (nerve-intact
      graft; brief denervation interval) or aneural (aneural graft; prolonged
      denervation interval) conditions of the fast-twitch extensor digitorum longus
      (EDL) muscle or the slow-twitch soleus muscle were performed in adult rat
      hindlimbs. MHC expression during skeletal muscle regeneration was determined
      sequentially using immunocytochemistry. RESULTS: After grafting, most muscle
      fibers in the EDL and soleus underwent ischemic degeneration and regeneration; at
      the periphery of each muscle, a few adult fibers survived. All regenerating
      fibers initially expressed embryonic/fetal (developmental) MHC alone, and
      subsequently both developmental and fast MHC. During the first week, no
      expression of slow MHC was observed in regenerating fibers in either the EDL or
      the soleus. In nerve-intact grafts, regenerating fibers expressed slow MHC as
      early as the second week; under aneural conditions, no regenerating fibers
      expressed slow MHC even 4 weeks after grafting. On the other hand, some
      persisting fibers in aneural grafts could maintain expression of slow MHC 4 weeks
      after grafting; other fibers underwent MHC transformation induced by denervation.
      No significant difference in MHC expression during regeneration was observed for
      slow compared with fast muscles, under either neural or aneural condition.
      CONCLUSIONS: These data suggest that regenerating adult skeletal muscle fibers,
      derived only from satellite cells, cannot express slow MHC without motor
      innervation, and that persisting muscle fibers, derived from both myoblasts in
      fetal development and satellite cells, may be intrinsically distinct from
      regenerating fibers. Satellite cells derived from slow and from fast muscles may
      be a single, homogenous population and may be the same population as fetal
      (secondary) myoblasts with regard to MHC expression.

PMID- 9655087
TI  - Involvement of liver-associated immunity in hepatic metastasis formation.
AB  - AIMS: Hepatic metastasis formation and prevention were studied from the viewpoint
      of liver-associated immunity. METHODS: RCN-9, a colonic cancer cell line derived
      from Fischer rats, and its subclone RCN-H4, in which the cancer is highly
      metastatic to the liver, were used. Fischer rats that were inoculated with parent
      RCN-9 colonic cancer cells (5 x 10(6)) via the portal vein showed liver
      metastasis in less than 60% of the animals. In contrast, all rats (100%) that
      received RCN-H4 produced multiple liver metastases. To investigate the difference
      of hepatic metastasis formation, we assessed the susceptibility of both cell
      lines against hepatic sinusoidal lymphocytes (HSL) by 51Cr-release assay, and the
      expression of MHC class I and class II of both cell lines by flow cytometry. In
      addition, we examined whether activation of HSL by interleukin-12 (IL-12) can
      prevent liver metastasis of highly metastatic clone RCN-H4. RESULTS: The RCN-H4
      clone showed decreased susceptibility to lysis by natural cytotoxic cells in HSL.
      This decrease in cell susceptibility was attributable to an increase in cell
      surface expression of MHC class I antigen. Administration of IL-12, a potent
      NK/CTL stimulatory cytokine, augmented the cytotoxic activity against the RCN-H4
      clone and prevented liver metastasis of RCN-H4 inoculated into the portal vein.
      CONCLUSIONS: Liver metastasis formation is positively correlated with the
      strength of the hepatic immune system which mainly consists of ontogenetically
      primitive T cells. As these effectors exert their cytotoxicity in a MHC
      nonrestricted fashion, tumor cells that highly express MHC class I antigen can
      readily avoid hepatic surveillance and apt to cause liver metastasis.
      Augmentation of the hepatic immune system, for instance, with IL-12
      administration, can prevent liver metastasis even in tumor cells with a high
      potential for liver metastasis.

PMID- 9655088
TI  - A rabbit model for metabolic studies after burn injury.
AB  - BACKGROUND: A rabbit burn model was developed and characterized, which will allow
      conduct of repeated, noninvasive and more sophisticated in vivo metabolic studies
      to explore the pathophysiology of burn injury, owing to its larger blood volume
      and tissue mass than the rat. MATERIALS AND METHODS: A 20% body surface, full
      thickness burn was applied to the backs of six anesthetized rabbits by immersion
      into a boiling-water bath for 10 s, followed by resuscitation with saline.
      Resting energy expenditure (REE) was measured daily in pre- and postburn periods.
      Whole body protein kinetics were evaluated using L-[1(-13)C]leucine tracer, on
      the preburn and the third postburn day. Fasting plasma glucose was also measured.
      RESULTS: A significant elevation of REE began on the second postburn day and
      reached 34 +/- 8% above the preburn level (P < 0.05, paired t test) on the third
      postburn day. The fasting plasma leucine flux and oxidation were significantly
      elevated from their preburn levels (both P < 0.05), indicating an accelerated
      proteolysis and a more negative body protein balance (P < 0.05); however, the
      rate of whole body protein synthesis did not differ significantly pre- and
      postburn injury. Fasting plasma glucose also increased (P < 0.001). on the third
      postburn day. The burn scar remained intact during the study, without any sign of
      infection. CONCLUSIONS: The metabolic changes observed in this animal model can
      be attributed to burn injury per se and they mimic those for flow phase in burn
      patients. This rabbit burn model should be suitable for exploring mechanistic
      aspects of the burn-induced changes in metabolism and nutrient balance.

PMID- 9655089
TI  - Evaluation of laser Doppler flowmetry to assess cyclosporine A-induced impairment
      of renal blood flow.
AB  - Cyclosporine A (CyA)-induced nephrotoxicity is a well-known complication of this
      potent immunosuppressive drug. It is caused by an elevation in renovascular
      resistance and impairment of renal blood flow. Currently, one of the principal
      experimental settings to assess renal hemodynamics has been using the in vivo
      fluorescent videomicroscopy (IVFV) method on hydronephrotic rat kidneys, which is
      expensive, time-consuming, not physiological, and not applicable to humans. In
      the present paper we have been able to confirm our working hypothesis that laser
      Doppler flowmetry (LDF) is a valuable tool for assessing microcirculatory changes
      in the rat kidney during CyA administration. Total subcapsular blood flow
      decreased to approximately 70% of baseline values (P < 0.05) and mean arterial
      pressure (MAP) increased initially to 113% of baseline values (P < 0.05) compared
      to only minor changes for cremophor (carrier substance) or no changes for sodium
      chloride solution 0.9%. LDF provides an easy and rapid technique and its major
      advantage is the potential use in assessing microcirculatory changes after kidney
      transplants in humans.

PMID- 9655090
TI  - Phospholipase A2 activities are decreased during early but increased during late
      phases of sepsis in rat heart.
AB  - BACKGROUND: Changes in the activities of secretory phospholipase A2 (sPLA2) and
      cytosolic phospholipase A2 (cPLA2) in the rat heart during early hyperdynamic and
      late hypodynamic phases of sepsis were studied in an attempt to understand the
      pathophysiology of cardiac dysfunction during sepsis. METHODS: Sepsis was induced
      by cecal ligation and puncture (CLP). Experiments were divided into three groups:
      control, early sepsis, and late sepsis. Early and late sepsis refers to those
      animals sacrificed at 9 and 18 h, respectively, after CLP. PLA2 activity was
      measured based on the rate of hydrolysis of 1-palmitoyl-2-[1-(14)C]-oleoyl
      phosphatidylcholine. RESULTS: The results show that under physiological
      conditions, sPLA2 and cPLA2 activities were time and protein dependent. The
      optimal Ca2+ concentrations for sPLA2 and cPLA2 activities were 3 mM and 40
      microM, respectively. During sepsis, sPLA2 activity was decreased by 25% (P <
      0.01) during early phase while it was increased by 49% (P < 0.01) during late
      phase of sepsis. Similarly, cPLA2 activity was decreased by 23% (P < 0.01) during
      early sepsis while it was increased by 60% (P < 0.01) during late sepsis.
      CONCLUSIONS: Since PLA2 functions to maintain cell membrane integrity and
      function, a biphasic change in sPLA2 and cPLA2 activities may contribute to the
      development of the two cardiodynamically distinct phases during the progression
      of sepsis.

PMID- 9655091
TI  - Visceral ischemia and neutrophil activation in sepsis and organ dysfunction.
AB  - BACKGROUND: It has previously been shown that a rise in intraoperative neutrophil
      CD11b expression during supracoeliac cross-clamping is a marker for subsequent
      development of postoperative organ dysfunction. Prolonged visceral ischemia and
      increased aneurysm extent are associated with higher risks of morbidity and
      mortality after TAAA repair. This study investigates the relationship between
      visceral ischemia and neutrophil activation in sepsis and organ dysfunction
      following visceral reperfusion. METHOD: Fifty-one patients undergoing
      supracoeliac cross-clamping, 5 patients undergoing suprarenal clamping, and 8
      patients undergoing infrarenal clamping for repair of aortic aneurysms were
      studied. Perioperative neutrophil CD11b expression was measured by flow
      cytometry. RESULTS: There was significant correlation between visceral clamp time
      and intraoperative CD11b expression. More extensive aneurysms resulted in
      increased visceral clamp times and CD11b expression. There were no differences
      between bypass and non-bypass-assisted surgery with regard to neutrophil
      expression. There were increased clamp time in patients who developed severe
      sepsis and postoperative organ dysfunction. Differences in preoperative levels of
      CD11b expression were observed between groups and high levels of preoperative
      CD11b expression were observed in patients who died intraoperatively, in type II
      patients who went on to develop severe sepsis and organ failure, and in patients
      who developed multiple organ failure rather than single organ failure.
      CONCLUSION: Longer periods of visceral ischemia are associated with higher levels
      of intraoperative CD11b expression, severe sepsis, and organ failure. High
      preoperative levels of CD11b may identify an "at-risk" subset of patients.

PMID- 9655092
TI  - Cardiopulmonary bypass primes polymorphonuclear leukocytes.
AB  - Polymorphonuclear leukocyte (PMN) superoxide (.O2-) production has been
      implicated in the pathogenesis of cardiopulmonary bypass (CPB)-related end organ
      injury. PMN "priming" has been described as an event which enhances the release
      of .O2- following a second, activating insult. We hypothesized that PMN priming
      occurs during CBP and is temporally related to the plasma level of complement
      (C3a), interleukin (IL)-6, and IL-8. PMNs were isolated from 10 CPB patients pre
      bypass (preCPB), 5 min after protamine administration (PROT), and at 6 and 24 h
      post-CPB. PMN .O2- production was measured by a cytochrome c reduction assay in
      the presence or absence of either phorbol 12-myristate-13-acetate (PMA, 0.4
      microgram/ml) or N-formyl-methionyl-leucyl-phenylalanine (FMLP, 1 microM) and
      also after priming with 2000 nM platelet-activating factor (PAF) followed by
      activation with either PMA or FMLP. Plasma levels of C3a, IL-6, and IL-8 were
      determined by enzyme-linked immunosorbent assay. PMA-activated PMN .O2-
      production was significantly elevated at 6 h post-CPB compared to pre-CPB levels
      (11.04 +/- 0.9 vs 7.62 +/- 0.57, P = 0.009), indicating that CPB is associated
      with in vivo PMN priming. When PMNs were primed in vitro with PAF and then
      activated with PMA or FMLP, .O2- release at 6 h post-CPB was also significantly
      greater than pre-CPB levels (16.04 +/- 0.74 vs 12.2 +/- 0.92, P = 0.038; and
      17.33 +/- 1.38 vs 13.33 +/- 1.35, P < 0.05), indicating that CPB acts
      synergistically with PAF to prime PMNs. Levels of C3a rose significantly over pre
      CPB levels at PROT (P = 0.001), and IL-6 and IL-8 rose over pre-CPB levels at 6 h
      post-CPB (P = 0.01 and P = 0.006, respectively). These findings demonstrate that
      CPB not only directly primes PMNs, but also potentiates priming of PMNs by PAF.
      This "primed" PMN state, which coincided with the increased plasma levels of
      inflammatory mediators, may suggest a mechanism of predisposition to organ
      dysfunction following CPB.

PMID- 9655093
TI  - Hospital-wide educational program decreases red blood cell transfusions.
AB  - BACKGROUND: Because of the numerous risks associated with the use of packed red
      blood cells (RBCs), it is critical that they be transfused only when appropriate.
      A hospital-wide educational program was developed in an attempt to improve the
      transfusion practices and provide a framework for blood bank audit at a Veterans
      Affairs teaching hospital. MATERIALS AND METHODS: The program required physicians
      to fill out an information sheet that listed appropriate criteria for
      transfusion. Charts were reviewed to determine if the transfusion met these
      criteria. If the transfusion was deemed inappropriate by peer review, the staff
      physician was notified by letter. The information sheet was used on a voluntary
      basis without chart review in 1989 and on a mandatory basis beginning in 1990.
      Transfusion rates and mortality were adjusted to patient days of hospitalization
      and evaluated using chi 2 analysis. RESULTS: While voluntary use did not affect
      transfusion rate, mandatory implementation resulted in a 26% decline (P < 0.001)
      between 1989 and 1990 in the number of RBC units transfused per patient days of
      hospitalization. A diminished use of RBCs persisted in the subsequent years.
      There was no increase in mortality during this time to suggest a detrimental
      effect from the decrease in RBC transfusion. No apparent variation in the
      hospital population could account for the changes. CONCLUSION: Use of a unique
      and simple transfusion request sheet as an educational tool resulted in improved
      transfusion practices at a Veteran Affairs teaching hospital.

PMID- 9655094
TI  - Comparative study of solutions for pulmonary preservation using an isolated
      rabbit lung model.
AB  - At the University of Minnesota, University of Wisconsin (UW), modified Euro
      Collins (MEC), and Marshall (M) solutions were compared as agents for pulmonary
      preservation in an isolated rabbit lung model. Normal saline (NS) was used as a
      control. The heart-lung blocks of donor rabbits were flushed with, and then
      preserved in, one of the solutions at 4 degrees C. Five rabbits were studied in
      each group. After 8 h of cold ischemia, the left lung was ventilated and
      reperfused with fresh venous blood from donor rabbits for 30 min. Pulmonary
      function was assessed by serial measurements of oxygen (O2) and carbon dioxide
      (CO2) tensions in blood obtained from the left atrial appendage. The ratios of
      wet/dry (W/D) weight of the lungs were calculated to assess the extent of
      pulmonary edema. After 8 h of preservation followed by 30 min of reperfusion, O2
      tension was significantly higher with UW (178.36 + 1.72 mmHg). The calculated P
      values were UW vs NS, < 0.0001; UW vs MEC, 0.154; and UW vs M, 0.0001. CO2
      tension with UW was also lower than the other solutions: UW, 35.8 +/- 0.698 mmHg;
      NS, 48.5 +/- 0.745 mmHg; MEC, 40.69 +/- 0.749 mmHg; and M, 44.68 +/- 0.697 mmHg.
      The calculated P value was UW vs NS, 0.0001; UW vs MEC, 0.0003; and UW vs M,
      0.0001 using repeated-measures analysis of covariance. The W/D ratio was lower
      with UW as well; UW, 6.82 +/- 0.19; NS, 8.01 +/- 0.23; MEC, 7.28 +/- 0.10; and M,
      7.34 +/- 0.17. The P value was < 0.001 using post-hoc tests. In this model, UW
      solution preserved the lungs better than the other three solutions tested and
      therefore warrants further clinical application.

PMID- 9655095
TI  - Let's keep our eye on the sparrow.

PMID- 9655096
TI  - Epiphyseal-metaphyseal enchondromatosis. A new clinical entity.
AB  - We reviewed the cases of eight unrelated children who had an unusual form of
      enchondromatosis characterized by unilateral enchondromas arising within the
      epiphyseal and metaphyseal regions of the long tubular bones of the lower
      extremity. Unlike previously described enchondromas, the lesions developed
      extensively within the epiphysis before closure of the growth plate and there was
      direct extension across the epiphyseal growth plate into the metaphysis. The
      lesions resulted in severe limb-length discrepancy and angular deformity (which
      increased in every patient after the time of presentation), asymmetrical
      premature physeal arrest, and joint incongruity, all of which necessitated
      numerous operative procedures. Seven patients had limb-lengthening and one had a
      Boyd amputation without lengthening. Five patients had a second lengthening
      procedure. Twenty-seven osteotomies (range, one to five procedures per patient)
      were done; six patients had a repeat osteotomy. Four patients had an
      epiphyseodesis. We believe that these lesions represent a previously undescribed
      clinical entity, which we termed epiphyseal-metaphyseal enchondromatosis.

PMID- 9655097
TI  - Distraction osteogenesis of the lower extremity with use of monolateral external
      fixation. A study of two hundred and sixty-one femora and tibiae.
AB  - We reviewed the results of distraction osteogenesis of 114 femora and 147 tibiae
      that had been lengthened to treat a variety of diagnoses. The femora had been
      lengthened an average of eleven centimeters (range, 3.5 to 17.0 centimeters), or
      48 per cent (range, 8 to 86 per cent) of the original femoral length. The average
      total time for the treatment of the femora (use of the fixator and any subsequent
      immobilization) was 257 days (range, 105 to 420 days). There were 114
      complications related to the femoral lengthenings, which led to eighty-seven
      additional operations. The tibiae were lengthened an average of nine centimeters
      (range, 3.0 to 15.6 centimeters), or 41 per cent (range, 9 to 100 per cent) of
      the original tibial length. The average total time for the treatment of the
      tibiae was 268 days (range, 110 to 497 days). There were 196 complications
      related to the tibial lengthenings, which led to 219 additional operations. The
      Achilles tendon was lengthened during or after seventy-three (50 per cent) of the
      tibial lengthenings. The femoral lengthenings that were performed to treat a limb
      length discrepancy were associated with significantly higher rates of
      complications overall (p = 0.010) and additional operations (p = 0.023) for each
      percentage of length gained than those that were performed to treat
      achondroplasia or another skeletal dysplasia. The femoral lengthenings that were
      performed to treat short stature (of an endocrine or idiopathic etiology) were
      also associated with higher rates of complications overall and additional
      operations than those performed to treat skeletal dysplasias, but the rates were
      lower than those for lengthenings performed to treat limb-length discrepancy. The
      rate of complications overall associated with femoral lengthening in patients who
      were fourteen years old or more was significantly higher than that associated
      with lengthening in patients who were less than fourteen years old (p = 0.047).
      Femoral lengthening through the metaphysis was associated with significantly
      higher rates of complications overall (p = 0.031) and additional operations (p =
      0.042) for each percentage of length gained than femoral lengthening through the
      diaphysis. The tibial lengthenings that were performed to treat Turner syndrome
      and idiopathic short stature were associated with significantly higher rates of
      complications overall (p = 0.026) and additional operations (p = 0.003) for each
      percentage of length gained than those performed to treat skeletal dysplasias.
      The rate of joint-related problems (p = 0.044) and that of additional operations
      (p = 0.053) after tibial lengthening in patients who were fourteen years old or
      more were significantly higher than those rates after tibial lengthening in
      patients who were less than fourteen years old. The site of the tibial osteotomy
      did not affect the rate of complications or additional operations. The femoral
      healing indices (in terms of both days per centimeter [p = 0.002] and days for
      each percentage of length gained [p = 0.019]) were significantly higher in the
      patients who were fourteen years old or more than in those who were less the
      fourteen years old. These values could not be used to predict an increase in the
      complications because of poor bone formation. The results of the present review
      suggest that the use of healing indices to gauge the final outcome of distraction
      osteogenesis is questionable; we were unable to discern significance or clinical
      importance from appropriately adjusted values.

PMID- 9655098
TI  - Radiographic results of arthrodesis with Cotrel-Dubousset instrumentation for the
      treatment of adolescent idiopathic scoliosis. A five to ten-year follow-up study.
AB  - We evaluated the radiographic results of posterior spinal arthrodesis with use of
      Cotrel-Dubousset instrumentation in seventy-six patients who had adolescent
      idiopathic scoliosis. At an average of six years (range, five to ten years)
      postoperatively, the fusion appeared to be solid in all patients. Comparison of
      radiographs that had been made immediately postoperatively with those that had
      been made at the time of the latest follow-up showed that no patient had lost any
      correction in the coronal plane at the levels with instrumentation and seventy
      five had had no change in the thoracic or lumbar sagittal alignment at the levels
      with or without instrumentation. In the remaining patient, a kyphosis had
      developed at the junction of the segments with instrumentation and those without
      instrumentation, necessitating additional operative treatment. Sixty-three
      patients completed a questionnaire for assessment of the clinical status. Their
      responses were favorable with regard to function, cosmetic appearance, and
      general satisfaction with the operative result. Twenty-four (38 per cent) of the
      sixty-three patients reported occasional pain in the spine that did not interfere
      with work or school activities. Sixty-two patients stated that, given the
      hypothetical situation of reverting to the preoperative status, they would have
      the operation again.

PMID- 9655099
TI  - Percutaneous radiofrequency coagulation of osteoid osteoma compared with
      operative treatment.
AB  - Osteoid osteoma, a benign bone tumor, has traditionally been treated with
      operative excision. A recently developed method for percutaneous ablation of the
      tumor has been proposed as an alternative to operative treatment. The relative
      outcomes of the two approaches to treatment have not previously been compared, to
      our knowledge. The rates of recurrence and of persistent symptoms were compared
      in a consecutive series of eighty-seven patients who were managed with operative
      excision and thirty-eight patients who were managed with percutaneous ablation
      with radiofrequency. Patients who had a spinal lesion were excluded. The minimum
      duration of follow-up was two years. There was a recurrence, defined as the need
      for subsequent intervention, after operative treatment in six (9 per cent) of
      sixty-eight patients who had been managed for a primary lesion and in two of
      nineteen who had been managed for a recurrent lesion. The average length of the
      hospital stay was 4.7 days for the patients who had a primary lesion and 5.1 days
      for those who had a recurrent lesion. There was a recurrence after percutaneous
      treatment in four (12 per cent) of thirty-three patients who had been managed for
      a primary lesion and in none of five who had been managed for a recurrent lesion.
      The average length of the hospital stay was 0.2 day for these thirty-eight
      patients. With the numbers available, we could detect no significant difference
      between the two treatments with regard to the rate of recurrence. The rate of
      persistent symptoms (that is, symptoms that did not necessitate additional
      treatment) was greater than the rate of recurrence. According to responses to a
      questionnaire, eight (30 per cent) of twenty-seven patients had persistent
      symptoms after operative treatment and six (23 per cent) of twenty-six patients
      had persistent symptoms after percutaneous treatment with radiofrequency. Two
      patients had complications after operative excision, necessitating a total of
      five additional operations. There were no complications associated with the
      percutaneous method. The results of the present study suggest that percutaneous
      ablation with radiofrequency is essentially equivalent to operative excision for
      the treatment of an osteoid osteoma in an extremity. The percutaneous method is
      preferred for the treatment of extraspinal osteoid osteoma because it generally
      does not necessitate hospitalization, it has not been associated with
      complications, and it is associated with a rapid convalescence.

PMID- 9655100
TI  - Interrelationships of clinical outcome, length of resection, and energy cost of
      walking after prosthetic knee replacement following resection of a malignant
      tumor of the distal aspect of the femur.
AB  - The relationships between the functional score according to the system of the
      International Society of Limb Salvage, the extent of resection, energy cost of
      walking, and gait characteristics were studied in thirty-six patients who had had
      segmental knee replacement after resection of a malignant tumor of the distal
      aspect of the femur. The mean free-walking velocity was 62.3 meters per minute
      (79 per cent of normal), which was a result of decreases in both cadence and
      stride length. The mean net energy cost during walking was 35 per cent greater
      than that of normal controls and correlated with the percentage of the femur that
      had been resected. All patients had decreased single-limb support time on the
      affected side compared with the unaffected side. There was a weak correlation
      between the asymmetry of the single-limb support time and the percentage of the
      femur that had been resected. The mean extensor torque of the affected knee was
      30 per cent that of the unaffected knee when one head of the quadriceps muscle
      had been excised, 19 per cent when two heads had been excised, 4 per cent when
      three heads had been excised, and 1 per cent when four heads had been excised.
      The patients who had had an extra-articular resection had lower mean extensor and
      flexor torques at the knee compared with those who had had an intra-articular
      resection. The asymmetry of the single-limb support time was inversely related to
      the residual extensor and flexor torques. The overall score according to the
      system of the International Society of Limb Salvage ranged from 17 to 29 points
      (mean, 24.6 points; 82 per cent of normal). The net energy cost, percentage of
      maximum aerobic capacity, and asymmetry of the single-limb support time had
      significant negative correlations with the overall functional score. Multivariate
      analysis showed that the overall functional score and the percentage of the femur
      that had been resected were the two most important factors that predicted the net
      energy cost. To our knowledge, this is the first objective validation of the
      functional score according to the system of the International Society of Limb
      Salvage. As the net energy cost can be predicted from universally available,
      inexpensive measures, investigators can easily use it as a clinical and research
      tool to evaluate prosthetic performance and to assess operative outcome.

PMID- 9655101
TI  - Arthroscopic repair of full-thickness tears of the rotator cuff.
AB  - We present the results of arthroscopic repair of full-thickness tears of the
      rotator cuff in seventy-three patients (thirty-nine men and thirty-four women).
      The average age of the patients at the time of the operation was 60.7 years
      (range, thirty-one to eighty-two years). All of the patients were followed for at
      least two years (average, thirty months; range, twenty-four to forty months). The
      shoulders were evaluated with the rating scale of the University of California at
      Los Angeles, the shoulder index of the American Shoulder and Elbow Surgeons, and
      the functional rating scale of Constant and Murley. In addition, the patients
      completed the Short-Form 36 Health Survey (SF-36) preoperatively and at the
      yearly follow-up evaluations. Eleven tears were small (less than one centimeter
      in length), forty-five were medium (one to three centimeters), eleven were large
      (more than three to five centimeters), and six were massive (more than five
      centimeters). The average length of the tear was twelve millimeters, and the
      average width was twenty-seven millimeters. Sixty-nine tendons were repaired
      anatomically, and four were repaired an average of three millimeters (range, two
      to eight millimeters) medial to the anatomical insertion of the tendon. An
      average of 2.3 (range, one to four) suture anchors were used in the repair. Sixty
      three glenohumeral joints were normal, and ten had an intra-articular lesion.
      Seven patients had a concomitant resection of the acromioclavicular joint. The
      average duration of the operation was fifty-six minutes (range, thirty-five to
      ninety minutes). The active and passive ranges of motion improved significantly
      after the procedure (p = 0.0001). The strength of resisted elevation improved
      from 7.5 to 14.0 pounds (3.4 to 6.3 kilograms) (p = 0.0001). The average total
      score according to the rating scale of the University of California at Los
      Angeles improved from 12.4 to 31.1 points; the average total score according to
      the shoulder index of the American Shoulder and Elbow Surgeons, from 30.7 to 87.6
      points; and the average absolute score according to the rating system of Constant
      and Murley, from 41.7 to 83.6 points (p = 0.0001 for all comparisons). The
      average score for the pain component of the rating scale of the University of
      California at Los Angeles improved from 2.4 to 8.6 points; fifty-seven (78 per
      cent) of the seventy-three patients rated the relief of pain as good or excellent
      on the visual-analog scale. The average score for satisfaction improved from 0.4
      to 4.6 points; sixty-six patients (90 per cent) rated their satisfaction as good
      or excellent at the time of the most recent examination. None of the shoulders
      were rated as good or excellent before the operation, whereas sixty-one (84 per
      cent) were so rated at the most recent follow-up evaluation after the index
      procedure. In addition, significant improvements (p = 0.0015) were noted in the
      scales and summary measures of the SF-36. Arthroscopic repair of full-thickness
      tears of the rotator cuff produced satisfactory results with regard to
      traditional orthopaedic criteria as well as with regard to patient-assessed
      criteria such as satisfaction, pain relief, and general health. The arthroscopic
      method offers several advantages, including smaller incisions, access to the
      glenohumeral joint for the inspection and treatment of intra-articular lesions,
      no need for detachment of the deltoid, and less soft-tissue dissection. However,
      these advantages must be considered against the technical difficulty of the
      method, which limits its application to surgeons who are skilled in both open and
      arthroscopic procedures on the shoulder.

PMID- 9655102
TI  - Long-term results of the Latarjet procedure for the treatment of anterior
      instability of the shoulder.
AB  - We performed ninety-five consecutive Latarjet procedures for the treatment of
      recurrent anterior instability of the shoulder between 1969 and 1983. In 1993, we
      retrospectively reviewed the clinical and radiographic results that were
      available for fifty-six patients (fifty-eight shoulders) who had been followed
      for an average of 143 years (range, ten to twenty-three years). The purpose of
      the study was to determine the prevalence of glenohumeral osteoarthrosis and the
      factors related to its development after the Latarjet procedure. The procedure
      was performed for the treatment of recurrent anterior dislocation in fifty
      shoulders and painful recurrent anterior subluxation in eight. All patients had a
      radiographic evaluation (three anteroposterior radiographs, with the humerus in
      external, neutral, and internal rotation, and one lateral radiograph) before the
      operation and at the latest follow-up examination. At the time of the latest
      follow-up, none of the patients had recurrent dislocation, six patients had
      apprehension with regard to possible dislocation, and one had occasional
      subluxation. According to the system of Rowe et al., fifty-one (88 per cent) of
      the fifty-eight shoulders had an excellent or good result; five (9 per cent), a
      fair result; and two (3 per cent), a poor result. Twenty-two shoulders had no
      glenohumeral osteoarthrosis. Thirty-four shoulders had centered glenohumeral
      osteoarthrosis (the humeral head remained in front of the center of the glenoid
      cavity), which was grade 1 in twenty-five shoulders, grade 2 in four, grade 3 in
      three, and grade 4 in two, and two shoulders had grade-4 eccentric glenohumeral
      osteoarthrosis (the humeral head was more proximal than normal in relation to the
      center of the glenoid cavity). Postoperative grade-1 glenohumeral osteoarthrosis,
      unlike the higher grades, had no effect on the function of the shoulder.

PMID- 9655103
TI  - Biomechanical effect of medial advancement of the supraspinatus tendon. A study
      in cadavera.
AB  - During the repair of some rotator-cuff tears, the torn tendon cannot be freed up
      adequately to permit reattachment at its original anatomical site of insertion.
      An option is to advance the site of insertion medially and reattach the tendon to
      a trough in the sulcus or to the humeral head. The biomechanical effects of such
      medial advancement on the moment arm of the supraspinatus muscle during
      glenohumeral elevation were studied in ten fresh-frozen shoulders from cadavera.
      Medial advancement of the site of insertion of the supraspinatus tendon was
      simulated by the placement of suture anchors in the sulcus of the proximal part
      of the humerus at points three, ten, and seventeen millimeters medial to the
      junction of the supraspinatus tendon and the bone. These distances were chosen
      not because they represent clinical options but because the large range allowed
      biomechanical study of medial advancement. Nylon lines were attached to the
      suture anchors and were passed back through an eyehook at the midpoint of the
      supraspinatus muscle. The excursion of each line was measured as the humerus was
      elevated, and the moment arm was estimated from the joint angle and excursion
      data with use of the principle of virtual work. Three and ten millimeters of
      medial advancement of the tendon (attachment in the sulcus) had a minimum (non
      significant) effect on the moment arm during elevation compared with the value
      determined for the intact condition. However, seventeen millimeters of medial
      advancement was found to reduce the moment arm significantly (p < 0.05).

PMID- 9655104
TI  - Revision total shoulder arthroplasty for the treatment of glenoid arthrosis.
AB  - The development of painful glenoid arthrosis is the most common reason for
      reoperation after replacement of the humeral head. We performed twenty-two
      revision total shoulder arthroplasties, between 1983 and 1992, for the treatment
      of painful glenoid arthrosis in shoulders that had a prosthetic replacement of
      the humeral head. Eighteen shoulders (seventeen patients) were included in the
      study as their preoperative and operative records were complete and they had been
      followed for at least two years (mean, 5.5 years; range, 2.3 to 10.0 years). The
      indications for the hemiarthroplasty were trauma (ten shoulders), osteoarthrosis
      (four), rheumatoid arthritis (two), and osteonecrosis secondary to the use of
      steroids (two). The mean interval between the hemiarthroplasty and the total
      shoulder replacement was 4.4 years (range, 0.8 to 12.7 years). The mean score for
      pain in the shoulder decreased from 4.3 points before the revision to 2.2 points
      after it (p = 0.0001). The mean active abduction increased from 94 degrees before
      the revision to 124 degrees after it (p = 0.01), and the mean external rotation
      increased from 32 to 58 degrees (p = 0.007). Two shoulders needed another
      operation after the revision because of a late infection in one and particulate
      synovitis associated with instability in the other. With the numbers available
      for study, we did not detect a significant difference in pain relief and range of
      motion with respect to gender, diagnosis, subluxation, or the presence of
      periprosthetic radiolucency. Our findings indicate that most patients with
      painful glenoid arthrosis after a hemiarthroplasty have marked pain relief and
      improvement in motion after revision to a total shoulder replacement. However,
      seven of the eighteen shoulders that had this procedure had an unsatisfactory
      result due to a limited range of motion or the need for a subsequent operation.
      Therefore, long-term studies are necessary to evaluate the durability of total
      shoulder replacement in this group of patients.

PMID- 9655105
TI  - The influence of active shear or compressive motion on fracture-healing.
AB  - The effects of interfragmentary sliding (shear) motion, axial motion, and locked
      external fixation on the healing of mid-tibial closed fractures were studied in
      fifty-six skeletally mature New Zealand White rabbits. The fractures were fixed
      with use of a four-pin, double-bar frame and were allowed to heal for either two
      or four weeks. Four experimental conditions were evaluated: transverse and
      oblique fractures treated with a locked external fixator (Groups 1 and 3,
      respectively), transverse fractures treated with an axially telescoping fixator
      (Group 2), and oblique fractures treated with a sliding oblique fixator (Group
      4). The maximum interfragmentary motion, recorded in vivo with an electronic
      motion sensor that was attached to the fixator, was 0.6 millimeter in Group 2
      during the first week and then declined rapidly. In contrast, the motion in Group
      4 exceeded 1.5 millimeters during the first week. The circumference of the callus
      in Group 4 was 11 to 23 per cent greater than that in the other groups at both
      two and four weeks (p < or = 0.02). At two weeks, torsional stiffness, strength,
      and energy absorption were comparable among Groups 1, 2, and 3. The increase in
      healing was most rapid for Group 4; by four weeks, the torsional strength and
      energy to failure of the fractures in Group 4 exceeded those in the other groups
      (p < or = 0.025) and reached or exceeded those of intact bone. Apparently,
      oblique sliding (shear) motion promoted greater cartilage differentiation and
      expansion of the peripheral callus than did axial motion or locked external
      fixation.

PMID- 9655106
TI  - Radioulnar load-sharing in the forearm. A study in cadavera.
AB  - Custom-designed miniature load-cells were inserted into the distal end of the
      ulna and the proximal end of the radius in ten fresh-frozen forearms from
      cadavera. The forces transmitted through the bones at these sites were measured
      under 134 newtons of constant axial load that was applied through the metacarpals
      as the forearm was rotated from 60 degrees of supination to 60 degrees of
      pronation. The simultaneous measurements of these forces allowed the calculation
      of radioulnar load-sharing at the wrist and the elbow as well as the calculation
      of the amount of force that was transferred from the radius to the ulna through
      the interosseous membrane. With the elbow in valgus alignment (that is, with
      contact between the radial head and the capitellum), the main pathway for load
      transmission through the forearm was direct axial loading of the radius;
      measurements from both load-cells were unaffected by the angle of elbow flexion.
      When the forearm was in neutral rotation, the mean force in the distal end of the
      ulna averaged 2.8 per cent of the load applied to the wrist and the mean force in
      the proximal end of the ulna averaged 11.8 per cent; this indicated that only a
      small amount of tension developed in the interosseous membrane. With the elbow in
      varus alignment (that is, with no contact between the radial head and the
      capitellum), load was transmitted through the forearm by a transfer of force from
      the radius to the ulna through the interosseous membrane. When the forearm was in
      neutral rotation, the force in the distal end of the ulna averaged 7.0 per cent
      of the load applied to the wrist and the force in the proximal end of the ulna
      averaged 93.0 per cent; the force through the interosseous membrane decreased
      with supination of the forearm. Testing with the elbow in valgus alignment and
      shortening of the distal end of the radius in two-millimeter increments produced
      corresponding increases in force in the distal end of the ulna and decreases in
      force in the radial head. The forces through the interosseous membrane remained
      low after each amount of radial shortening.

PMID- 9655107
TI  - Fracture-dislocation of the humerus with intrathoracic displacement of the
      humeral head. A case report.

PMID- 9655108
TI  - Early detection of osteochondritis dissecans of the capitellum in young baseball
      players. Report of three cases.

PMID- 9655109
TI  - Hallux rigidus and osteoarthrosis of the first metatarsophalangeal joint.

PMID- 9655110
TI  - The prospective, randomized, double-blind clinical trial in orthopaedic surgery.

PMID- 9655111
TI  - A meta-analysis of the efficacy of non-operative treatments for idiopathic
      scoliosis.

PMID- 9655112
TI  - Resurfacing of the patella in total knee arthroplasty. A prospective, randomized,
      double-blind study.

PMID- 9655113
TI  - Resurfacing of the patella in total knee arthroplasty. A prospective, randomized,
      double-blind study.

PMID- 9655114
TI  - Resurfacing of the patella in total knee arthroplasty. A prospective, randomized,
      double-blind study.

PMID- 9655115
TI  - Recruitment curve of the soleus H reflex in patients with neurogenic
      claudication.
AB  - The diagnosis of neurogenic claudication (NC) remains uncertain when no definite
      signs of radicular lesions are found in electrophysiological testing. However,
      the functional deficit could be demonstrated during the brief time in which the
      patients complain of pain and weakness in the muscles of the lower limbs after
      walking. We have used electrophysiological testing of the H reflex and the F wave
      to document the transient functional derangement expected to occur at the
      radicular level in patients with NC after walking. We examined the recruitment
      curve of the soleus H reflex, and the chronodispersion of the posterior tibial
      nerve F wave, at rest and after a walking exercise that triggered their symptoms
      in 10 patients with NC, with no positive electrophysiological findings of
      radicular lesion. The same studies were performed in 5 age-matched healthy
      volunteers, used as control subjects, who were asked to walk for 30 min. At rest
      before walking, no abnormalities were found in any of the patients. After
      walking, the H wave showed a transient increase in its threshold with respect to
      that of the M wave in 7 patients (70%). Such abnormality lasted for a mean period
      of 7 min. In 2 of these patients there was also an increase in the F-wave
      chronodispersion. Our data suggest that nerve conduction is transiently blocked
      in large myelinated fibers at a radicular level in patients with NC after
      walking. Partial interruption of the H-reflex circuit could be one of the
      pathophysiological mechanisms underlying NC.

PMID- 9655116
TI  - Alternative dystrophin gene transcripts in golden retriever muscular dystrophy.
AB  - Golden retriever muscular dystrophy (GRMD), the canine model of Duchenne muscular
      dystrophy (DMD), is caused by a splice site mutation in the dystrophin gene. This
      mutation predicts a premature termination codon in exon 8 and a peptide that is
      5% the size of normal dystrophin. Western blot analysis of skeletal muscle from
      GRMD dogs reveals a slightly truncated 390-kD protein that is approximately 91%
      the size of normal dystrophin. This 390-kD dystrophin suggests that GRMD dogs,
      like some DMD patients, employ a mechanism to overcome their predicted
      frameshift. Reverse-transcriptase polymerase chain reaction on GRMD muscle has
      revealed two in-frame dystrophin transcripts which lack either exons 3-9 or exons
      5-12. Both transcripts could be translated into a dystrophin protein of
      approximately 390 kD. An understanding of how truncated dystrophin is produced in
      GRMD may allow this mechanism to be manipulated toward a potential therapy for
      DMD.

PMID- 9655117
TI  - Median and ulnar nerve conduction studies among workers: normative values.
AB  - To determine normative values for nerve conduction studies among workers, we
      selected a subset of 326 workers from 955 subjects who participated in medical
      surveys in the workplace. The reference cohort was composed exclusively of active
      workers, in contrast to the typical convenience samples. Nerve conduction
      measures included bilateral median and ulnar sensory amplitude and latency (onset
      and peak). Workers with upper extremity symptoms, medical conditions that could
      adversely affect peripheral nerve function, low hand temperature, or highly
      repetitive jobs were excluded from the "normal" cohort. Linear regression models
      explained between 21% and 51% of the variance in nerve function, with covariates
      of age, sex, hand temperature, and anthropometric factors. The most robust models
      were fitted for sensory amplitudes in the median and ulnar nerves for dominant
      and nondominant hands. The median-ulnar difference was least sensitive to
      adjustment, indicating it is the best measure to use if corrections are not made
      to account for relevant covariates. A key point was that the magnitude of
      variance increased with age and anthropometric factors. These findings provide
      strong evidence that to improve diagnostic accuracy, electrodiagnostic testing
      should control for relevant covariates, particularly age, sex, hand temperature,
      and anthropometric factors.

PMID- 9655118
TI  - Longitudinal study of skeletal muscle adaptations during immobilization and
      rehabilitation.
AB  - This study describes the metabolic, morphologic, neurologic, and functional
      adaptations observed in the plantar flexors during 8 weeks of lower leg
      immobilization and 10 weeks of physical therapy following ankle surgery. A
      combination of magnetic resonance imaging and spectroscopy, isokinetic and
      isometric muscle testing, and simple functional tests revealed many adaptive
      changes due to immobilization, including atrophy, loss of muscle strength,
      reduced central activation, increase in fatigue resistance, and an increase in
      inorganic phosphate content. After 10 weeks of physical therapy all alterations
      were reversed, with the exception of a remaining 5.5% deficit in total muscle
      cross-sectional area.

PMID- 9655119
TI  - Electrophysiological determination of the site involved in generating abnormal
      muscle responses in hemifacial spasm.
AB  - In patients with hemifacial spasm (HFS), abnormal muscle responses due to
      abnormal cross-transmission are observed in facial muscles. However, the site in
      the facial nerve responsible for the cross-transmission remains a matter of
      controversy. We have developed a model in which by considering the
      electrophysiological parameters involved in producing the abnormal muscle
      response, we can determine the site of the abnormal cross-transmission within the
      facial nerve. This model was applied to HFS patients with three different
      etiologies: idiopathic, post-Bell's palsy, and post-XII-VII anastomosis. Our data
      show that: in idiopathic HFS, the cross-transmission may occur in the facial
      nerve at the level of the pontocerebellar angle; in post-Bell's palsy, it is
      inside the petrous bone; and in XII-VII anastomosis, it must be in the
      extracranial part of the facial nerve. The possible mechanisms for this cross
      talk are discussed in terms of ephaptic transmission or of a central
      hyperexcitability in the facial motor nucleus.

PMID- 9655120
TI  - Disruption and reorganization of sodium channels in experimental allergic
      neuritis.
AB  - The axonal distribution of voltage-dependent Na+ channels was determined during
      inflammatory demyelinating disease of the peripheral nervous system. Experimental
      allergic neuritis was induced in Lewis rats by active immunization. In diseased
      spinal roots Na+ channel immunofluorescence at many nodes of Ranvier changed from
      a highly focal ring to a more diffuse pattern and, as the disease progressed,
      eventually became undetectable. The loss of nodal channels corresponded closely
      with the development of clinical signs. Electrophysiological measurements and
      computations showed that a lateral spread of nodal Na+ channels could contribute
      significantly to temperature sensitivity and conduction block. During recovery
      new clusters of Na+ channels were seen. In fibers with large-scale demyelination,
      the new aggregates formed at the edges of adhering Schwann cells and appeared to
      fuse to form new nodes. At nodes with demyelination limited to paranodal
      retraction, Na+ channels were often found divided into two symmetric highly focal
      clusters. These results suggest that reorganization of Na+ channels plays an
      important role in the pathogenesis of demyelinating neuropathies.

PMID- 9655121
TI  - Facilitation of human first dorsal interosseous muscle responses to transcranial
      magnetic stimulation during voluntary contraction of the contralateral homonymous
      muscle.
AB  - The size of compound motor evoked potentials (cMEPs) to transcranial magnetic
      stimulation of the motor cortex was measured in the relaxed first dorsal
      interosseous muscle of the nondominant hand (ndFDI) during different levels of
      voluntary contraction in the homonymous muscle of the dominant hand (dFDI). cMEP
      responses in the ndFDI became larger when the dFDI was contracted to forces
      ranging 10-70% of maximum voluntary contraction. Variability in the amplitude of
      the cMEP responses in ndFDI decreased when dFDI was contracted. Comparison with
      cMEPs to spinal cord stimulation suggested a large component of the facilitation
      was occurring at a cortical level. The amplitude of cMEP responses in ndFDI also
      increased when the tibialis anterior muscle of the leg on the contralateral side
      was contracted. The observed facilitation of motoneurons during contraction of
      contralateral muscles might involve a transcallosal pathway modulating the
      excitability of one cortex when the other is activated.

PMID- 9655122
TI  - The delayed depolarization in rat cutaneous afferent axons is reduced following
      nerve transection and ligation, but not crush: implications for injury-induced
      axonal Na+ channel reorganization.
AB  - Two distinct populations of Na+ channels (kinetically fast and slow) are present
      on the cell bodies and axons of cutaneous afferent neurons; the fast current is
      increased and the slow current reduced in amplitude following nerve injury. The
      present study was undertaken to determine if similar changes occur on the axons
      of these neurons following peripheral nerve injury. The compound action
      potentials from rat sural nerves were recorded in a sucrose gap chamber.
      Following application of 4-aminopyridine, a prominent and well-characterized
      depolarization (the delayed depolarization) followed the action potential. This
      potential, only present on cutaneous afferent axons, has been correlated with
      activation of a slow Na+ current. The delayed depolarization was reduced after
      nerve transection. The refractory period of transmission of the action potential
      was shortened in the transected nerves, but that of the delayed depolarization
      was prolonged. The changes were largest when the sural nerve was cut and ligated
      [control: 38.1 +/- 1.7% (n = 5); injury: 24.5 +/- 2.8% (n = 5), P < 0.05], which
      prevented reconnection to its peripheral target. When the nerve was crushed and
      allowed to reestablish peripheral target connections, the delayed depolarization
      was minimally effected. These results indicate that the changes in Na+ channel
      organization following peripheral target disconnection observed on cutaneous
      afferent cell bodies also occur on their axons.

PMID- 9655123
TI  - Functional magnetic stimulation of the respiratory muscles in dogs.
AB  - This study assessed the ability of functional magnetic stimulation (FMS) to
      activate the respiratory muscles in dogs. With the animal supine, FMS of the
      phrenic nerves using a high-speed magnetic stimulator was performed by placing a
      round magnetic coil (MC) at the carotid triangle. Following hyperventilation
      induced apnea, changes in volume (deltaV) and airway pressure (deltaP) against an
      occluded airway were determined. FMS of the phrenic nerves produced substantial
      inspired function (deltaV = 373 +/- 20.5 mL and deltaP = -20 +/- 2.0 cm H2O).
      After bilateral phrenectomies, maximal inspired deltaV (219 +/- 12.2 mL) and
      deltaP (-10 +/- 1.0 cm H2O) were produced when the MC was placed near the C6-C7
      spinous processes, while maximal expired deltaV (-199 +/- 22.5 mL) and deltaP (11
      +/- 2.3 cm H2O) were produced following stimulation near the T9-T10 spinous
      processes. We conclude: (1) FMS of either the phrenic or upper intercostal nerves
      results in inspired volume production; (2) FMS of the lower intercostal nerves
      generates expired volume production; and (3) FMS of the respiratory muscles may
      be a useful noninvasive tool for artificial ventilation and assisted cough in
      patients with spinal cord injuries or other neurological disorders.

PMID- 9655124
TI  - Polyneural innervation in the psoas muscle of the developing rat.
AB  - Polyneural innervation was studied in the psoas muscle in developing rats from P4
      till P25 and at adult age, with the combined silver-acetylcholinesterase
      technique. Nerve endings were counted, and end-plates were measured. These data
      were compared with such data in the human. The end of polyneural innervation in
      the rat (around P20) and in the human (around 12 weeks postterm age) in both
      cases coincides with a transformation in motor behavior and postural control. The
      rat's psoas muscle at early stages is less heavily innervated than this muscle in
      the human. Up to three axons per motor end-plate were counted at P4, but in the
      human up to five axons at 25 weeks of post menstrual age. This difference might
      be related to the lower percentage of type I muscle fibers in the rat.

PMID- 9655125
TI  - Myoglobin as a polymerase chain reaction (PCR) inhibitor: a limitation for PCR
      from skeletal muscle tissue avoided by the use of Thermus thermophilus
      polymerase.
AB  - Skeletal muscle tissue contains polymerase chain reaction (PCR) inhibitors that
      are coextracted by conventional nucleic acid extraction procedures. Myoglobin, a
      heme-containing molecule, was shown to act as a potent Thermus aquaticus DNA
      polymerase inhibitor and is likely to be involved in muscle tissue-associated PCR
      inhibition. The use of Thermus thermophilus DNA polymerase avoids muscle tissue
      associated PCR inhibition, and should be used in case of small amounts or
      instability of the targeted nucleic acid.

PMID- 9655126
TI  - Walking and fatigue in multiple sclerosis: the role of the corticospinal system.
AB  - Transcranial magnetic stimulation was used to study motor evoked potentials
      (MEPs) of leg muscles in controls and patients with multiple sclerosis (MS)
      before and after walking. In controls, MEP areas were significantly reduced after
      walking. A similar or greater reduction was seen in most patients, although there
      was a wide range of values. The M waves were unchanged. We conclude that walking
      induces functional changes of the corticospinal system and/or connected neurons
      contributing to central fatigue, especially in patients with MS.

PMID- 9655127
TI  - Macrophage apoptosis in muscle tissue in experimental autoimmune myasthenia
      gravis.
AB  - Combining in situ tailing and immunocytochemical staining, we demonstrated that
      the infiltrating macrophages in muscle tissue sections during early phase of
      experimental autoimmune myasthenia gravis (EAMG) in Lewis rats were eliminated by
      apoptosis at high frequency. These apoptotic macrophages were colocalized in the
      end-plate regions. Apoptosis is a major cause for elimination of infiltrating
      macrophages during the early phase of EAMG.

PMID- 9655128
TI  - The effect of age and temperature on mdx muscle fatigue.
AB  - We have studied the in vitro contractile and fatigue characteristics of extensor
      digitorum longus (EDL) muscles from 8- and 62-week-old dystrophin-deficient (mdx)
      and control mice at 20 degrees C and 35 degrees C. There were no differences in
      fatigability at 20 degrees C, but at 35 degrees C the dystrophin-deficient
      muscles demonstrated increased fatigability compared to controls, with the older
      mice exhibiting the greatest fatigue. These results suggest a temperature-related
      mechanism of myofibrillar fatigue in dystrophin-deficient EDL muscles.

PMID- 9655129
TI  - Pseudometabolic expression and phenotypic variability of calpain deficiency in
      two siblings.
AB  - Two siblings originating from Reunion Island were affected by a limb-girdle
      muscular dystrophy (LGMD) type 2A and carried the same two mutations in the
      calpain gene: 946-1 AG-->AA, affecting a splice site, and S744G. They
      demonstrated the clinical variability possible with calpain-3 mutations. Onset
      was around 20 years of age in each of them. The girl's symptoms mimicked a
      metabolic myopathy, while her brother, at the same age, presented a classical
      phenotype of LGMD in an advanced functional stage.

PMID- 9655130
TI  - Diagnostic yield of stimulation and voluntary single-fiber electromyography in
      myasthenia gravis.
AB  - Voluntary and stimulation single-fiber electromyography were performed in the
      extensor digitorum communis muscle of 15 myasthenic patients. The increase in
      mean and individual mean consecutive difference as well as the proportion of
      blocking in the volitional activation were greater than in the stimulation
      method. These differences may be explained in part by the different degree of
      alteration in large as compared with small motor units in patients with
      myasthenia gravis.

PMID- 9655131
TI  - Conduction block in vasculitic neuropathy.
AB  - Vasculitis involving peripheral nerves usually presents as an acute asymmetrical
      axonal neuropathy. We report a 67-year-old man with a symmetrical subacute
      neuropathy in which nerve conduction studies showed prominent conduction block, a
      finding indicative of demyelination. Sural nerve biopsy showed a vasculitic
      neuropathy with invasion of blood vessel walls by inflammatory cells and a
      mixture of nerve fiber loss and demyelination. The demyelination in this case was
      presumably a consequence of subinfarctive nerve ischemia.

PMID- 9655132
TI  - The effect of temperature on nerve conduction parameters in carpal tunnel
      syndrome.
AB  - Correction factors exist to allow for the dramatic effect that temperature has on
      nerve conduction study parameters. However, these are based on normal nerves in
      normal individuals and may not be appropriate in the diseased nerve setting. Our
      clinical study showed that in carpal tunnel syndrome, the median nerve reacts
      differently to temperature changes compared with normal ulnar controls.
      Furthermore, statistically significant differences exist between the rates of
      change with increasing temperature in motor and sensory nerves.

PMID- 9655133
TI  - Sports and peripheral nerve injuries: report of 190 injuries evaluated in a
      single electromyography laboratory.
AB  - We retrospectively reviewed electrodiagnostic studies performed on 169 athletes
      with 190 sports injuries to nerve fibers. Eighty-eight percent of the injuries
      were to the upper extremity. Athletes participated in 27 sports, but over one
      third of injuries were sustained playing football. The most common injuries were
      burners (n = 38) and cervical radiculopathies (n = 18), followed by median (n =
      28), axillary (n = 22), ulnar (n = 19), suprascapular (n = 14), and peroneal (n =
      11) mononeuropathies. This is the largest reported series of sports-related nerve
      injuries.

PMID- 9655134
TI  - Lack of association between outcome measures of nerve regeneration.
AB  - Studies of nerve regeneration in rodents utilize at least one of three classes of
      outcome measures: electrophysiology, morphometry, and functional tests. The
      assumption that these measures are correlated was tested utilizing a data set of
      16 variables. Significant correlations (Spearman's rho, P < or = 0.05) were found
      within variable classes; however, none were found between classes. The three
      commonly utilized outcome measures do not measure the same phenomenon but rather
      discrete aspects of nerve regeneration.

PMID- 9655135
TI  - The contemporary role of F-wave studies. F-wave studies: clinical utility.

PMID- 9655136
TI  - The contemporary role of F-wave studies. F-wave studies: limitations.

PMID- 9655137
TI  - Bilateral femoral neuropathy during pregnancy.

PMID- 9655138
TI  - Acute isolated ophthalmoplegia as a variant of Miller-Fisher syndrome.

PMID- 9655139
TI  - Single-fiber electromyography improvement with 3,4-diaminopyridine in Lambert
      Eaton myasthenic syndrome.

PMID- 9655140
TI  - Significance of facial and trigeminal nerve involvement in Charcot-Marie-Tooth
      disease type 1A: a case report.

PMID- 9655141
TI  - Cerebral edema, cell volume regulation, and the role of ion channels in organic
      osmolyte transport.

PMID- 9655142
TI  - Identification of the volume-sensitive organic osmolyte/anion channel in human
      glial cells.
AB  - Cellular use of small organic solutes known as organic osmolytes for regulation
      of the volume of the cell is a universal biological phenomenon. During swelling,
      cells open an anion channel which allows for efflux of these solutes. This
      channel is known as the volume-sensitive organic osmolyte/anion channel (VSOAC).
      Anion channels with properties identical to VSOAC were found in human brain cells
      obtained following pediatric neurosurgical procedures. The tissues examined
      included tumors as well as putatively normal gray and white matter astrocytes.
      The cells activated an anion conductance when swollen by hypotonic shock.
      Baseline currents in these cells were generally small and increased up to 30-fold
      within 10 min following the onset of swelling. The anion channel activated by
      swelling was outwardly rectified and inactivated by depolarization, both
      characteristic of the VSOAC. These observations indicate that human glial cells
      and tumor cells activate VSOAC following cellular swelling. This suggests that
      organic osmolyte efflux can be modulated during brain swelling by pharmaceuticals
      which modulate VSOAC.

PMID- 9655143
TI  - Endoscopic washout: a new technique for treating chronic subdural hematomas in
      infants.
AB  - Chronic hematomas are a common problem during infancy and usually occur as the
      consequence of trauma. They tend to enlarge and are often managed successfully
      with repeated subdural taps. In patients with collections that fail to respond to
      percutaneous drainage, the choice of operative management, including burr hole
      evacuation, shunting, or craniotomy, remains controversial. A new technique,
      called endoscopic washout, was successfully used in 7 children under the age of 2
      years who presented with irritability, vomiting, seizures, and rapid head growth.
      Preoperative computerized tomography (CT) scans demonstrated enlarging,
      bilateral, chronic subdural collections; these failed to respond to repeated
      percutaneous taps over 10 days. With the patient positioned supine, bilateral
      linear incisions were made anterior to the coronal suture in the midpupillary
      lines and burr holes were placed. After the dura and outer membrane were opened
      and coagulated with bipolar cautery, a 4-mm steerable fiberscope was introduced
      into the subdural space to visualize the collections, evacuate any residual clot,
      and continuously irrigate the space with lactated Ringer's solution warmed to
      physiologic temperature. No bridging vessels or synechiae were violated; nitrous
      oxide and hyperventilation were discontinued before removing the fiberscope. The
      subdural space was irrigated again prior to closure. At follow-up (range 18
      months to 8 years), CT scans showed reexpansion of the brain and no
      reaccumulation of the hematomas. We conclude that the endoscopic washout is a
      safe, uncomplicated treatment for chronic subdural hematomas in infants; is more
      effective than treatment with conventional burr holes alone, and eliminates the
      need for shunting or craniotomy.

PMID- 9655144
TI  - Neoadjuvant chemotherapy for hypervascular malignant brain tumors of childhood.
AB  - Some large hypervascular brain tumors pose an exceptional challenge to surgical
      resection, particularly in young children with small blood volumes. To limit
      blood loss during resection of hypervascular tumors, the authors used upfront
      chemotherapy as the primary treatment modality in 2 young children. This produced
      a dramatic reduction in tumor size and vascularity and greatly facilitated
      definitive surgical removal.

PMID- 9655145
TI  - Three-dimensional reconstruction and surgical navigation in pediatric epilepsy
      surgery.
AB  - We have used MRI-based three-dimensional (3D) reconstruction and a real-time,
      frameless, stereotactic navigation device to facilitate the removal of seizure
      foci in children suffering from intractable epilepsy. Using this system, the
      location of subdural grid and strip electrodes is recorded on the 3D model to
      facilitate focus localization and resection. Ten operations were performed,
      including 2 girls and 8 boys ranging in age from 3 to 17, during which 3D
      reconstruction and surgical instrument tracking navigation was used. In all the
      cases, the patients tolerated the procedure well and showed no postoperative
      neurological deficits. We believe this to be a valuable tool for a complete and
      safe resection of seizure foci, thereby reducing the incidence of postoperative
      neurological deficits and significantly improving the overall quality of life of
      the patients.

PMID- 9655146
TI  - On the surgical treatment of refractory epilepsy in tuberous sclerosis complex.
AB  - The role of surgery in the treatment of refractory epilepsy (RE) in tuberous
      sclerosis complex (TSC) is poorly defined. Four patients with RE and TSC were
      evaluated for epilepsy surgery from 1994 to 1996. Three of four patients
      developed infantile spasms within 5 months of birth. These progressed to frequent
      complex partial and generalized tonic/myoclonic seizures refractory to
      antiepileptic drug therapy. Neuroimaging revealed typical findings of TSC
      including calcified lesions consistent with hamartomas. Clinical and EEG evidence
      suggested an epileptic focus near a prominent lesion in each child. This was
      confirmed using magnetic source imaging in 1 case. All patients underwent
      inpatient continuous video-EEG monitoring followed by temporal lobectomy or focal
      cortical resection with intraoperative EEG. Age at operation ranged from 5 to 13
      years. Three out of 4 patients experienced a greater than 90% decrease in seizure
      activity. One patient continues to have rare complex partial seizures, and 1 has
      rare simple partial seizures. Tumor DNA analysis revealed mutations in the TSC1
      gene in case 1 and the TSC2 gene in case 2; no mutations have been identified yet
      in cases 3 and 4. Temporal lobectomy and focal cortical resection can result in
      improved seizure control in patients with TSC and RE.

PMID- 9655147
TI  - ISG viewing wand-guided endoscopic catheter placement for treatment of posterior
      fossa CSF collections.
AB  - Six patients presented with either entrapped fourth ventricles or
      noncommunicating cerebrospinal fluid collections of the posterior fossa requiring
      drainage. These collections were treated with shunt systems whose proximal
      catheter was placed into the fourth ventricle via a coronal burr hole using an
      endoscope guided by Eleckta's ISG Viewing Wand. The technique and its advantages
      are described as are the complications and early outcomes.

PMID- 9655148
TI  - Sinus pericranii: neuroradiologic findings and clinical management.
AB  - We report an 11-year-old boy with a sinus pericranii. Magnetic resonance images
      demonstrated a small hole in the cranium underneath the subcutaneous mass.
      Magnetic resonance angiography (MRA) with sequential two-dimensional time-of
      flight (2D-TOF) method demonstrated that the venous flow via the sinus pericranii
      was directed from the intra- to the extracranial venous system (the drainer
      type). This was confirmed by a combination of conventional cerebral angiography
      and percutaneous sinography. We advocate that both the correct diagnosis and
      classification of sinus pericranii can be established with a combination of
      current noninvasive neuroradiologic studies, especially for the pediatric age
      group. MRA with the 2D-TOF method is useful in the assessment of this venous
      anomaly.

PMID- 9655149
TI  - Beta-blockers and ultrafiltration failure.

PMID- 9655150
TI  - Creatinine clearance and urea clearance in peritoneal dialysis: what to do in
      case of discrepancy.

PMID- 9655151
TI  - The role of Na,K-ATPase inhibitors in hypertension and end-stage renal disease.
AB  - OBJECTIVE: To review the role of Na,K-ATPase inhibitors in the pathogenesis of
      essential hypertension and hypertension associated with end-stage renal disease.
      DATA SOURCES: MEDLINE search, 1966 to 1997. RESULTS: There is a suggestive
      physiologic and epidemiologic relationship between Na,K-ATPase inhibition and
      hypertension. However, clearance data cannot support the hypothesis that
      differential metabolism of this family of compounds explains the improved
      hypertensive control seen in patients on peritoneal dialysis compared to those on
      hemodialysis. CONCLUSIONS: As a result of the complex methodologies involved, it
      is unclear whether Na,K-ATPase inhibitors play a significant role in the
      hypertension of end-stage renal disease in general and peritoneal dialysis in
      particular.

PMID- 9655152
TI  - Beta-blockers may cause ultrafiltration failure in peritoneal dialysis patients.
AB  - OBJECTIVE: To elucidate mechanisms of ultrafiltration failure (UFF) in patients
      on continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Retrospective
      analysis of patients with UFF during CAPD compared with cross-sectionally
      selected controls. SETTING: University peritoneal dialysis center. PATIENTS:
      Thirteen patients with UFF during CAPD necessitating change to hemodialysis (n =
      6) or continuous cycling peritoneal dialysis (n = 1), or causing greatly
      increased need for high glucose-containing solutes, were compared with 18 CAPD
      patients without such problems. STATISTICS: Fisher's exact test, Student's
      independent t-test, univariate and multivariate correlation analyses. MAIN
      OUTCOME MEASURES: Data were collected prior to analyses. RESULTS: Systolic blood
      pressure and total cholesterol and triglyceride levels were higher in the UFF
      patients than in the controls (p = 0.006, p = 0.028, p = 0.013). Beta-blockers
      were used by 12 of the UFF patients, but only 2/ 18 controls (p < 0.0001). There
      was no intergroup difference in number of women, patient age or weight, incidence
      of diabetes or previous peritonitis, duration of PD, serum levels of albumin,
      creatinine, iron, or ferritin, or dosage of erythropoietin. Correlation was found
      between the daily amount of glucose instilled into the abdomen and serum
      triglycerides (r = +0.72, p < 0.001), total cholesterol (r = +0.56, p = 0.008),
      and HbA1C (r =-0.41, p = 0.039). Many patients were high absorbers of dialysis
      glucose. CONCLUSION: The study indicates that beta-blockers may cause UFF, and
      that glucose and lipid metabolism differed between these patients and controls
      without UFF.

PMID- 9655153
TI  - Effect of bicarbonate-based dialysis solutions on intracellular pH (pHi) and
      TNFalpha production by peritoneal macrophages.
AB  - OBJECTIVE: To compare the effect of Dianeal and two newly-formulated bicarbonate
      based peritoneal solutions on intracellular pH (pHi), tumor necrosis factor-alpha
      (TNFalpha) mRNA level, and TNFalpha secretion by peritoneal macrophages (PMphi).
      DESIGN AND MEASUREMENTS: Peritoneal macrophages were isolated from dialysates
      collected after overnight dwells in peritonitis-free continuous ambulatory
      peritoneal dialysis patients. Dialysis solutions contained 1.5% or 4.25%
      dextrose. HCO3 concentrations of bicarbonate-(TB) and bicarbonate/lactate
      buffered (TBL) solution were 38 mM and 25 mM, respectively. TBL also contained
      lactate at a concentration of 15 mM. pCO2 levels were 78 mmHg and 51 mmHg,
      respectively. In all experiments pCO2 was carefully maintained at a stable level.
      The pHi was measured by spectrofluorometry in BCECF-loaded PMphi exposed to
      different dialysis solutions or Hank's balanced salt solution. TNFalpha levels
      were measured by ELISA in the supernatant of lipopolysaccharide- (LPS) stimulated
      PMphi after their incubation in different solutions for 15 and 30 minutes.
      TNFalpha mRNA was measured by reverse transcriptase polymerase chain reaction (RT
      PCR) of total RNA extracted from LPS-stimulated PMphi after their incubation in
      different solutions for 30 minutes. beta-actin mRNA was used as the control.
      RESULTS: Dianeal caused a profound drop in pHi to below 6.2. Following an initial
      drop, pHi stabilized after 4 minutes at levels of 6.96 and 6.8 after incubation
      in TB and TBL, respectively. In comparison to the control solution, a fall of 11%
      and 21% in TNFalpha secretion was seen after incubation in TB for 15 and 30
      minutes, respectively, and 15% and 26% after incubation in TBL. Under identical
      conditions, Dianeal (Baxter, McGaw Park, IL, U.S.A.) caused 59% and >95%
      suppression of TNFalpha secretion. Accordingly, TNFalpha mRNA level in PMphi was
      severely depressed by Dianeal but no detectable inhibition was observed following
      incubation for 30 minutes in TB and TBL. When dextrose concentration in TB and
      TBL was increased from 1.5% to 4.25%, TNFalpha secretion by PMphi was not
      suppressed by more than 49%, even after 30 minutes incubation. Moreover,
      suppression of TNFalpha mRNA levels could not be detected with TB or TBL even at
      high dextrose concentrations. CONCLUSIONS: In contrast to Dianeal, both
      bicarbonate-based solutions caused only a mild drop in pHi of PMphi. We postulate
      this effect to be responsible for the improved capacity of PMphi to secrete
      TNFalpha when incubated in bicarbonate-based solutions compared to Dianeal.
      Reflecting its known cytotoxicity, dextrose in high concentrations diminishes the
      protective effect of TB and TBL on immune function of PMphi. TBL is as effective
      as TB in preventing the deleterious effect of Dianeal on PMphi function.

PMID- 9655154
TI  - Calcium concentration in the CAPD dialysate: what is optimal and is there a need
      to individualize?
AB  - OBJECTIVE: To evaluate risk/benefit of various continuous ambulatory peritoneal
      dialysis (CAPD) dialysate calcium concentrations. DATA SOURCES: A review of the
      literature on the effects of various CAPD dialysate Ca concentrations on plasma
      Ca, plasma phosphate, plasma parathyroid hormone (PTH), doses of calcium
      carbonate, doses of vitamin D analogs, and requirements of aluminum-containing
      phosphate binders. STUDY SELECTION: Eleven studies of nonselected CAPD patients,
      and 13 studies of CAPD patients with hypercalcemia were reviewed. RESULTS: In
      nonselected CAPD patients, treatment with a reduced dialysate Ca concentration
      (1.00, 1.25, or 1.35 mmol/L) improved the tolerance to calcium carbonate and/or
      vitamin D metabolites and reduced the need for Al-containing phosphate binders.
      When using dialysate Ca 1.25 or 1.35 mmol/L, the initial decrease of plasma Ca
      and increase of PTH could easily be reversed with an immediate adjustment of the
      treatment. After 3 months, stable plasma Ca and PTH levels could be maintained
      using only monthly investigations. In patients with hypercalcemia and elevated
      PTH levels, treatment with dialysate Ca concentrations below 1.25 mmol/L implied
      a considerable risk for the progression of secondary hyperparathyroidism. When
      hypercalcemia was present in combination with suppressed PTH levels, a controlled
      increase of PTH could be obtained with a temporary discontinuation of vitamin D
      and/or a reduction of calcium carbonate treatment in combination with a dialysate
      Ca concentration of 1.25 or 1.35 mmol/L. CONCLUSION: Most CAPD patients can be
      treated effectively and safely with a reduced dialysate Ca concentration of 1.35
      or 1.25 mmol/L. Treatment with dialysate Ca concentrations below 1.25 mmol/L
      should not be used. A small fraction of patients with persistent hypocalcemia
      need treatment with high dialysate Ca, such as 1.75 mmol/L.

PMID- 9655155
TI  - Touch contamination of connection devices in peritoneal dialysis--a quantitative
      microbiologic analysis.
AB  - OBJECTIVE: To determine the level of bacterial contamination associated with
      touch contact of a connector set during peritoneal dialysis (PD). DESIGN: The
      experiment utilized a laboratory-based simulation of a bag exchange procedure.
      Deliberate touch contamination of the connector set spike was followed by
      quantitative recovery of micro-organisms from the connector and, in some cases,
      the dialysis bag. SUBJECTS: Patients undergoing PD were used as the "test" group.
      Departmental secretarial and laboratory staff served as the comparative control
      group. SETTING: The patients were voluntary subjects from a PD outpatients unit
      and were tested in their own homes. OUTCOME: The numbers of micro-organisms
      contaminating a connector set and entering the dialysis bag during a touch
      contamination event were determined. Additionally we identified hand hygiene and,
      in particular, the care taken to dry the hands after washing as being highly
      relevant to microbial touch-contamination levels. Patient hand disinfection, as
      practised in most PD units, effectively reduced touch contamination to low
      levels. RESULTS: Touch contamination of a connector set with unprepared hands led
      to fewer than 100 micro-organisms translocating from fingers to the spike. If the
      hands were washed but not dried before touch contact was made, up to 4500 micro
      organisms translocated to the connector set spike. Air-towel drying of washed
      hands before touch contact reduced the translocating numbers by 95%-99%. Hand
      disinfection, as routinely practiced by PD patients, reduced the bacterial
      numbers reaching the peritoneal cavity after touch contamination to <5. The range
      of micro-organisms isolated from the fingers of PD patients using hand
      disinfectants on a regular basis showed considerably more diversity than the
      control group. CONCLUSION: Hand care prior to bag exchange has a major effect on
      touch-contamination levels. Accidental touch contact of connecting devices by
      unprepared hands using a PD-bag exchange procedure leads to the translocation of
      500 micro-organisms or fewer to the connector device. If the hands are wet at the
      time of contact the number translocating can be as high as 4500. Hand drying with
      an air towel before touch contact reduces the numbers translocating by 95%-99%.
      Hand disinfection procedures carried out prior to bag exchange minimizes touch
      contamination levels.

PMID- 9655156
TI  - Symptomatic ascites after discontinuation of continuous peritoneal dialysis.
AB  - OBJECTIVE: To analyze pathogenetic associations, clinical features, management,
      and outcome of ascites following discontinuation of continuous peritoneal
      dialysis (CPD). DESIGN: Retrospective analysis of symptomatic ascites, defined as
      ascites requiring at least one therapeutic paracentesis, developing in patients
      who discontinued CPD. SETTING: Dialysis unit of one tertiary care center.
      PARTICIPANTS: Twelve patients with 13 episodes of symptomatic ascites diagnosed
      soon after (a few days to 2 months) discontinuation of CPD. INTERVENTIONS:
      Diagnostic tests to characterize the pathogenesis of ascites; management of
      ascites by hemodialysis or CPD. MAIN OUTCOME MEASURES: Evolution of clinical
      features and nutritional parameters, survival. RESULTS: Ascites was infectious in
      3 episodes (non-tuberculous mycobacterial peritonitis) and noninfectious in the
      remaining 10 episodes. Serum-to-ascites albumin concentration gradient (AG) was
      6.3 +/- 1.5 g/L in infectious ascites and 17.3 +/- 2.7 g/L ( >11 g/L in every
      episode) in noninfectious ascites. Infectious ascites was managed with
      hemodialysis, prolonged courses of antimicrobial agents, and repeated
      paracentesis. Paracentesis ceased after 3-9 months. The patients were alive after
      52 +/- 19 months. Seven episodes of noninfectious ascites were managed by
      hemodialysis and repeated paracentesis. Five patients died within 6 months from
      cardiac causes or sepsis. The remaining 2 patients died after 14 and 16 months
      from cardiac causes. Three episodes of noninfectious ascites in 2 patients were
      treated by restarting CPD within 2-5 months. Patients were alive at 16.9 +/- 13.2
      months. They were asymptomatic and achieved fluid control. On the same CPD
      schedule, peritoneal clearances of urea and creatinine and normalized protein
      nitrogen appearance were unchanged between the initial and restarted CPD. Serum
      albumin was 33.3 +/- 2.5 g/L at the end of the first CPD period, 23.6 +/- 2.5 g/L
      soon after restarting CPD, and 31.3 +/- 5.5 g/L 4 months after restarting CPD.
      CONCLUSIONS: Noninfectious ascites after discontinuation of CPD is often
      characterized by an AG > 11 g/L, suggesting portal hypertension. Restarting CPD
      in noninfectious ascites may be associated with improvement in ascites
      symptomatology and nutritional parameters and with satisfactory survival.

PMID- 9655158
TI  - Computerized kinetic modeling: a new tool in the quest for adequacy in peritoneal
      dialysis.
AB  - Until recently, kinetic modeling of peritoneal dialysis (PD) was performed by
      engineers, scientists, or nephrologists at major teaching institutions. Now there
      are several "user-friendly" computer programs which permit the practicing
      nephrologist and dialysis staff to monitor adequacy of the individual PD patient
      and to optimize the dialysis prescription. In this brief article, the
      capabilities, methods, and data requirements of three programs are reviewed, and
      specific recommendations for the selection of a particular program are discussed.

PMID- 9655157
TI  - Peritoneal dialysis in children under 5 years of age.
AB  - OBJECTIVE: We report our experience with maintenance peritoneal dialysis (PD) in
      small children. DESIGN: This is a retrospective analysis of the patient records
      of all children under the age of 5 years treated with continuous peritoneal
      dialysis (CPD) between 1986 and 1994 in Finland. SETTING: Treatment was started
      and the patients were seen at the outpatient clinic at the Hospital for Children
      and Adolescents, University of Helsinki, every 3 months. Between these visits,
      they had controls at their local hospital every 2-4 weeks. PATIENTS: The most
      common primary renal disease in these 34 patients was congenital nephrotic
      syndrome of the Finnish type (27 patients). Others were: congenital nephrotic
      syndrome (3 patients), polycystic kidney disease (1), urethral valve (1),
      neuroblastoma (1), and renal dysplasia (1). RESULTS: Mean age at onset was 1.6
      years and median treatment time 9.3 months. Time spent in hospital decreased from
      270 days/year in the 1980s to 150 days/year in the 1990s. Two children died
      (5.9%). The peritonitis rate on continuous cyclic peritoneal dialysis was 1:11.5
      patient-months. Hernias were diagnosed in 29% of the patients. After 3 months
      half of the patients were on antihypertensive medication. Pulmonary edema was
      diagnosed once in 12 patients and twice in 2 patients. During the first 6 months
      on PD the mean height standard deviation score (hSDS) increased from -2.13 to 
      1.66 (p < 0.0001). The 6-month change in hSDS before initiation and 6 months
      after the start of CPD increased from -0.12 +/-0.68 to +0.59 +/- 0.64 (p =
      0.0008). CONCLUSIONS: Our results indicate that peritoneal dialysis is feasible
      and safe in small children. Mortality was low and growth was good. The major
      challenges presented by CPD therapy were maintenance of optimal nutrition,
      avoidance of peritonitis, and control of volemia.

PMID- 9655159
TI  - Abdominal catastrophe: visceral injury as a cause of peritonitis in patients
      treated by peritoneal dialysis.
AB  - OBJECTIVE: Peritonitis is considered an acceptable and controllable risk in
      patients undergoing chronic peritoneal dialysis (PD). In contrast, peritonitis
      due to visceral leakage represents a true "abdominal catastrophe" because of
      striking morbidity and mortality. To delineate the incidence, causes, and
      outcomes of catastrophic peritonitis, we compared patients who developed
      peritonitis due to documented visceral leakage with patients who developed
      peritonitis due to enteric organisms without evidence of visceral leakage.
      DESIGN: Retrospective chart review. SETTING: PD Unit located in tertiary care
      referral center. PATIENTS: 230 patients treated by PD between January 1988 and
      June 1996. MAIN OUTCOME MEASURES: All episodes of PD-related peritonitis
      occurring over an 8-year period. Hospital course of all patients with or without
      renal failure who were treated at University Hospitals of Cleveland for ischemic
      bowel disease, cholecystitis, viscus perforation, or diverticulitis. RESULTS:
      Anatomically documented visceral injury caused 32.5% of episodes of enteric
      bacterial peritonitis in 72 patients between January 1988 and June 1996. The
      overall incidence of this "abdominal catastrophe" was 11.3%, or 26 of a total of
      230 patients treated by PD. Of the 26 patients, 50% died, 30.7% survived but
      switched permanently to hemodialysis, and only 19.2% remained on, or returned to,
      PD. Compared to renal failure patients treated by hemodialysis or transplantation
      and to non-renal failure patients, the incidence of abdominal catastrophe was 20
      60 times greater in patients treated by PD. CONCLUSIONS: Evidence for injury of
      an abdominal organ should be sought in all patients treated by PD who develop
      peritonitis with enteric organisms. Surgical intervention is definitive for
      diagnosis, and if performed early may reduce morbidity and mortality.

PMID- 9655160
TI  - Increased endothelin-1 mRNA expression in peripheral blood monocytes of dialysis
      patients.
AB  - OBJECTIVE: To compare plasma endothelin (ET)-1 level and ET-1 mRNA level in
      peripheral blood monocytes of patients undergoing hemodialysis (HD) or continuous
      ambulatory peritoneal dialysis (CAPD). DESIGN: Endothelin-1 mRNA level in
      peripheral blood monocytes and plasma ET-1 level were studied in 30 HD patients,
      15 CAPD patients, 20 chronic renal failure patients not being dialyzed, and 20
      normal healthy controls. Hemodialysis patients were dialyzed three times per week
      with a bicarbonate dialysate. Different types of dialyzer membrane, viz.,
      cellulose triacetate, cuprophane, polysulfone, polyacrylonitrile, and
      ethylenevinylalcohol were used in 8, 6, 6, 5, and 5 patients, respectively.
      Continuous ambulatory peritoneal dialysis patients were dialyzed with four daily
      exchanges of a 2-L dialysate containing glucose at a concentration of 1.5% to
      2.5%. RESULTS: Higher levels of ET-1 mRNA in monocytes were observed in HD
      patients than in CAPD patients (p < 0.01), chronic renal failure patients (p <
      0.01), or normal healthy controls (p < 0.001). The level of ET-1 mRNA in
      monocytes at the end of HD was not significantly higher than that at the start of
      HD. In addition, these mRNA levels in HD patients showed little difference with
      different types of dialysis membrane. Plasma ET-1 level in HD patients (10.2 +/-
      2.4 pg/mL) was also higher than that in CAPD patients (7.8 +/- 1.6 pg/mL, p <
      0.01), in chronic renal failure patients (4.8 +/- 1.2 pg/mL, p < 0.01), or in
      normal controls (2.6 +/- 0.8 pg/mL, p < 0.001). CONCLUSION: Dialysis itself did
      not significantly affect ET-1 mRNA levels in monocytes. Chronic stimulation of
      peripheral blood monocytes may be associated with higher levels of ET-1 mRNA and
      plasma ET-1 in HD patients than in CAPD patients.

PMID- 9655162
TI  - Pasteurella multocida peritonitis in peritoneal dialysis patients: beware of the
      cat.

PMID- 9655161
TI  - Serum disaccharides and osmolality in CCPD patients using icodextrin or glucose
      as daytime dwell.
AB  - OBJECTIVE: To evaluate the safety, efficacy, and biocompatibility of icodextrin-
      and glucose-containing dialysis fluid during continuous cycling peritoneal
      dialysis (CCPD), patients were treated for 2 years with either icodextrin- or
      glucose-containing dialysis fluid for their daytime dwell (14-15 hours). Prior to
      entry into the study, all patients used a standard glucose solution (Dianeal
      1.36%, 2.27%, or 3.86%, Baxter, Utrecht, The Netherlands). DESIGN: Open,
      randomized, prospective, two-center study. SETTING: University hospital and
      teaching hospital. PATIENTS: Both established and patients new to CCPD were
      included. A life expectancy of more than 2 years, a stable clinical condition,
      and written informed consent were necessary before entry. Patients aged under 18,
      those with peritonitis in the previous month, and women of childbearing
      potential, unless taking adequate contraceptive precautions, were excluded.
      Thirty-eight patients entered the study, and 25 (13 glucose, 12 icodextrin) had a
      follow-up period of 12 months or longer in December 1996. MAIN OUTCOME MEASURES:
      Serum icodextrin metabolites: one to five glucose units (G1-G5), a high molecular
      weight fraction (G > 10), and total carbohydrate level, as well as a biochemical
      profile were determined every 3 months in combination with all other study
      variables. RESULTS: In icodextrin-treated patients, serum disaccharide (maltose)
      concentrations increased from 0.05 +/- 0.01 (mean +/- SEM) at baseline, to an
      average concentration in the follow-up visits of 1.14 +/- 0.13 mg/mL (p < 0.001).
      All icodextrin metabolites increased significantly from baseline, as illustrated
      by the serum total carbohydrate minus glucose levels: from 0.42 +/- 0.05 mg/mL to
      an average concentration in the follow-up visits of 5.04 +/- 0.49 mg/mL (p <
      0.001). At the same time, serum sodium levels decreased from 138.1 +/- 0.7 mmol/L
      to an average concentration in the follow-up visits of 135.4 +/- 0.8 mmol/L (p <
      0.05). However, after 12 months the serum sodium concentration increased
      nonsignificantly (NS) from baseline to 136.6 +/- 0.9 mmol/L, after an initial
      decrease. Serum osmolality increased significantly from baseline in icodextrin
      users at 9 and 12 months, but did not differ significantly from glucose users in
      any visit. In icodextrin-treated patients, the calculated serum osmolal gap
      increased significantly from 4.1 +/- 1.4 mOsm/kg to an average of 11.8 +/- 1.7
      mOsm/kg (p < 0.01). The sum of the serum icodextrin metabolites in
      millimoles/liter equaled the increase in osmolal gap. Body weight increased in
      icodextrin users (71.9 +/- 2.8 kg to 77.8 +/- 3.0 kg; NS). Clinical adverse
      effects did not accompany these findings. Residual renal function remained stable
      during follow-up. CONCLUSIONS: The serum icodextrin metabolite levels in the
      present study increased markedly and were the same as those found previously in
      continuous ambulatory peritoneal dialysis patients treated with icodextrin,
      despite the longer dwell time for CCPD patients (14-16 hr versus 8-12 hr). The
      initial decrease in serum sodium concentration was followed by an increase to a
      concentration not different from baseline at 12 months. The pathophysiology of
      this finding is speculated. Calculated osmolal gap in icodextrin patients
      increased significantly (p < 0.01) at every follow-up visit, and could be
      explained by the serum icodextrin metabolite increase. We encountered no clinical
      side effects of the observed levels of icodextrin metabolites.

PMID- 9655164
TI  - No risk for peritonitis by sampling with a modified PET.

PMID- 9655163
TI  - A simplified laparoscopic salvage technique for malfunctioning chronic peritoneal
      dialysis catheters.

PMID- 9655165
TI  - Brevibacterium iodinum peritonitis associated with acute urticaria in a CAPD
      patient.

PMID- 9655166
TI  - Chronic administration of iron dextran into the peritoneal cavity of rats.

PMID- 9655167
TI  - Potential problem: delayed detection of peritonitis by patients receiving home
      automated peritoneal dialysis (APD)

PMID- 9655168
TI  - Vancomycin-resistant enterococci and empirical vancomycin for CAPD peritonitis.

PMID- 9655169
TI  - Monoarthritis in a patient with lupus nephritis on peritoneal dialysis.

PMID- 9655170
TI  - Peritoneal dialysis case forum. Was CAPD the answer to this patient's complex
      problems?

PMID- 9655171
TI  - Literature. November-December 1997.

PMID- 9655172
TI  - Nursing application: Handwashing and other gripping nursing issues.

PMID- 9655173
TI  - Expression and localization of insulin-like growth factor-1 in normal and post
      burn hypertrophic scar tissue in human.
AB  - The migration of epithelial cells from dermal appendages toward the wound surface
      is essential for re-epithelialization of partial thickness burn injuries. This
      study provides evidence that these cells in vivo synthesize a mitogenic and
      fibrogenic factor, insulin-like growth factor-1 (IGF-1), which may promote the
      development of the post-burn fibroproliferative disorder, hypertrophic scarring
      (HSc). An evaluation of 7 post-burn hypertrophic scars, 7 normal skin samples
      obtained from the same patients and 4 mature scars revealed that IGF-1 expressing
      cells from the disrupted sweat glands tend to reform small sweat glands of 4-10
      cells/gland in post-burn HSc. The number of these cells increases with time and
      the glands become larger in mature scar. Other epithelial cells such as those
      found in sebaceous glands and basal and suprabasal keratinocytes, also express
      IGF-1 protein and mRNA as detected by Northern and RT-PCR analysis of RNA
      obtained from whole skin and separated epidermis and dermis. However, cultured
      keratinocytes did not express mRNA for IGF-1. Histological comparisons between
      normal and HSc sections show no mature sebaceous glands in dermal fibrotic
      tissues but the number of IGF-1 producing cells including infiltrated immune
      cells was markedly higher in the dermis of hypertrophic scar tissues relative to
      that of the normal control. In these tissues, but not in normal dermis, IGF-1
      protein was found associated with the extracellular matrix. By in situ
      hybridization, IGF-1 mRNA was localized to both epithelial and infiltrated immune
      cells. Collectively, these findings suggest that in normal skin, fibroblasts have
      little or no access to diffusible IGF-1 expressed by epithelial cells of the
      epidermis, sweat and sebaceous glands; while following dermal injury when these
      structures are disrupted, IGF-1 may contribute to the development of fibrosis
      through its fibrogenic and mitogenic functions. Reformation of sweat glands
      during the later stages of healing may, therefore, limit this accessibility, and
      lead to scar maturation.

PMID- 9655174
TI  - Inhibition of DNA topoisomerase I activity by heparan sulfate and modulation by
      basic fibroblast growth factor.
AB  - Eukaryotic DNA topoisomerase I catalyzes changes in the superhelical state of
      duplex DNA by transiently breaking single strands thereby allowing relaxation of
      both positively and negatively supercoiled DNA. Topoisomerase I is a nuclear
      enzyme localized at active sites of transcription, and abnormal levels of the
      enzyme have been observed in a variety of neoplasms. Because the enzyme binds
      heparin and, given the presence of heparan sulfate within the nuclei of mammalian
      cells, we sought to investigate the interaction between topoisomerase I and
      sulfated glycosaminoglycans isolated from normal and neoplastic human liver. The
      results demonstrated that low concentrations (approximately 100 nM) of heparan
      sulfate from normal liver but not from its malignant counterpart effectively
      blocked relaxation of supercoiled DNA driven by either purified holoenzyme or
      topoisomerase I activity present in nuclear extracts of three malignant cell
      lines. Heparin acted at even lower (approximately 10 nM) concentrations.
      Moreover, we show that basic fibroblast growth factor could interfere with this
      heparan sulfate/heparin-driven inhibition and that both basic fibroblast growth
      factor and heparin-binding sites co-localized in the nuclei of U937 leukemic
      cells. Our results suggest that DNA topoisomerase I activity may be modulated in
      vivo by specific heparan sulfate moieties present in normal cells but markedly
      reduced or absent in their transformed counterparts.

PMID- 9655175
TI  - Inhibition of neuronal nitric oxide synthase (n-cNOS) reverses the corticotrophin
      induced behavioral effects in rats.
AB  - The nitric oxide (NO) synthase inhibitor NG-monomethyl-L-arginine (N-NMMA) and
      the competitive substrate for NO synthase L-arginine were used to determine the
      role of endogenous NO on the behavioral and neuroendocrine responsiveness
      following systemic corticotrophin in dexamethasone-suppressed rats.
      Corticotrophin (50-200 mU/kg, s.c.) dose-dependently decreased behavioral
      activity in the actimeter and produced significant anxiolytic and anti-risk
      activity in the plus-maze behavior test, without affecting systolic blood
      pressure. Rats given corticotrophin showed significant increased plasma
      corticosterone and reduced adrenal ascorbic acid level. These behavioral and
      adrenal responses of corticotrophin were dose dependently blocked by metyrapone
      (20 and 50 mg/kg, i.p.), an inhibitor of steroid 11beta-hydroxylase in adrenal
      and neural tissues that block steroidogenesis. Intracerebroventricular
      administration of L-NMMA (20 microg/rat in 10 microl) significantly prevented the
      behavioral hypoactivity and anxiolytic-like responses of corticotrophin without
      influencing the adrenal responsiveness. The effect of L-NMMA was completely
      reversed by preadministration of L-arginine (300 mg/kg, i.p.). These results
      suggest that neuronal nitric oxide pathway plays an important modulating role in
      the behavioral effects of corticotrophin by mechanisms other than those involving
      cardiovascular effects.

PMID- 9655176
TI  - Endothelin-1 and insulin activate the steady-state voltage dependent R-type Ca2+
      channel in aortic smooth muscle cells via a pertussis toxin and cholera toxin
      sensitive G-protein.
AB  - In single rabbit aortic smooth muscle cells, and at a concentration known to
      induce a maximum sustained increase of intracellular Ca2+ via activation of the
      steady-state voltage dependent R-type Ca2+ channels, endothelin-1 (10(-7) M) and
      insulin (80 microU/ml) were found to induce a sustained increase in cytosolic
      free Ca2+ ([Ca]i) levels that was significantly attenuated by pre-treatment with
      either pertussis toxin (PTX), cholera toxin (CTX) or removal of extracellular
      Ca2+. However, both PTX and CTX failed to inhibit the sustained depolarization
      evoked sustained Ca2+ influx and [Ca]i elevation via activation of the R-type
      Ca2+ channels. Moreover, ET-1 and insulin-evoked sustained increases in Ca2+
      influx were not attenuated by the selective PKC inhibitor, bisindolylmaleimide
      (BIS), or the specific L-type Ca2+ channel blocker, nifedipine, but were
      completely reversed by the R-type Ca2+ channel blocker, (-) PN 200-110
      (isradipine). These data suggest that both insulin and ET-1 activate the
      nifedipine-insensitive but isradipine-sensitive steady state voltage dependent R
      type Ca2+ channels present on rabbit VSMCs and these channels are directly
      coupled to PTX and CTX sensitive G protein(s).

PMID- 9655177
TI  - Ascorbate-Fe2+ lipid-peroxidation of rat liver microsomes: effect of vitamin E
      and cytosolic proteins.
AB  - In the present study, we examined the effect of the intraperitoneal
      administration of vitamin E (100 mg/kg weight/24 h) on ascorbate (0.4 mM) induced
      lipid peroxidation of rat liver microsomes . We also analyzed the effect of
      hepatic cytosolic proteins on this process. The results indicate that the
      ascorbate induced light emission was 76% lower in microsomes (1 mg protein)
      obtained from vitamin E treated animals when compared with controls. In the
      presence of cytosolic protein (1 mg) the chemiluminescence of control microsomes
      diminished 55.8 and 59.5% when cytosol from controls and treated animals was
      used, respectively. The chemiluminescence of vitamin E microsomes diminished
      25.03 and 22.08% when both types of cytosol were added to the medium. Dialyzed or
      treated at 70 degrees C cytosol was also able to inhibit the lipid peroxidation
      of either control or vitamin E rat liver microsomes. By means of gas
      chromatography we analyzed the fatty acid composition of native and peroxidated
      microsomes from both animal groups. The peroxidation affected principally
      arachidonic acid and its diminution was more evident in the control microsomes
      than in the microsomes from the vitamin E treated group. By HPLC we analyzed the
      vitamin E content in all subcellular fractions employed. In microsomes from the
      vitamin E-group, the content of vitamin was 11 times higher than in the control
      ones (0.678 +/- 0.1038 vs. 0.062 +/- 0.0045 microg alpha-tocopherol/mg protein,
      respectively), while levels in the cytosol from the vitamin E-group were only 2
      times higher than in the control cytosol (0.057 +/- 0.0051 vs. 0.025 +/- 0.0015
      microg alpha-tocopherol/mg protein, respectively).

PMID- 9655178
TI  - Association of myeloperoxidase with heparin: oxidative inactivation of proteins
      on the surface of endothelial cells by the bound enzyme.
AB  - Chromatography of human myeloperoxidase (MPO) on a heparin-agarose column
      demonstrated a tight association of the protein with the resin. The
      electrophoretic mobility of mixtures of MPO and heparin in polyacrylamide gels
      under nondenaturing conditions was consistent with a strong interaction of the
      cationic enzyme with the polyanionic polysaccharide. Purified MPO prebound to
      bovine aorta endothelial cells (BAEC) and supplemented with hydrogen peroxide
      dose- and time-dependently abrogated the interaction of coagulation factor IX
      (FIX) with factor IX-binding protein (FIXBP) on the surface of BAEC reflecting
      oxidative modification of the binding protein. This inactivation of FIXBP
      required the presence of chloride implicating hypochlorite in the reaction.
      Hypochlorite and activated neutrophils exerted a similar effect. The oxidative
      modification of FIXBP was only partially dependent on the addition of hydrogen
      peroxide and was abolished by exogenous heparin which displaced MPO from the cell
      surface, emphasizing the functional differences between cell-bound and free
      enzyme.

PMID- 9655179
TI  - Possible mechanism of captopril induced endothelium-dependent relaxation in
      isolated rabbit aorta.
AB  - The mechanism of captopril, an angiotensin converting enzyme (ACE) inhibitor with
      sulfhydryl group (SH) in its structure, to produce an endothelium-dependent
      vasorelaxation was studied. In rabbit aorta with intact endothelium and
      precontracted with phenylephrine, captopril and superoxide dismutase (SOD)
      produced dose-dependent relaxation. Lisinopril, an ACE inhibitor without a -SH
      group in its structure, did not produce endothelium-dependent relaxation. It was
      observed that captopril, like SOD, produced the relaxation by protecting the EDRF
      from getting inactivated by superoxide anions as pyrogallol and methylene blue
      inhibited both the captopril and SOD-mediated relaxation. The free radical
      scavenging action of captopril is further substantiated by the observation that
      captopril, but not lisinopril, inhibited FeCl3/ascorbic acid-induced lipid
      peroxidation in whole tissue homogenates of rabbit aorta to a level comparable to
      that of SOD. These results suggest that endothelium-dependent vasodilation
      produced by captopril may be due to its ability to scavenge superoxide anion and
      this property may be ascribed to the -SH group present in its structure.

PMID- 9655180
TI  - An alpha subunit-deficient form of eukaryotic protein synthesis initiation factor
      eIF-2 from rabbit reticulocyte lysate and its activity in ternary complex
      formation.
AB  - Eukaryotic protein synthesis initiation factor eIF-2 is usually isolated as a
      heterotrimer (alphabeta gamma). By use of Sephacryl S-300 fractionation an alpha
      subunit-deficient form of eIF-2 was identified in impure preparations from rabbit
      reticulocyte lysate and it appeared in these preparations to be still active in
      formation of the ternary complex (eIF-2.GTP.Met-tRNAi). Subsequently alpha
      subunit-deficient eIF-2 was further purified and this appeared to have retained
      ternary complex forming activity. Together with a suggested lack of involvement
      of the beta subunit this implies that the alpha subunit was not required for
      activity and the gamma subunit bound both GTP and Met-tRNAi in formation of the
      ternary complex. The identification and study of alpha subunit-deficient eIF-2
      thus elucidated the involvement of the subunits in binding of GTP and Met-tRNAi
      to produce the ternary complex in polypeptide chain initiation.

PMID- 9655181
TI  - Hyperosmolality-induced abnormal patterns of calcium mobilization in smooth
      muscle cells from non-diabetic and diabetic rats.
AB  - Hyperglycemia and/or hyperosmolality may disturb calcium homeostasis in vascular
      smooth muscle cells (SMCs), leading to altered vascular contractility in
      diabetes. To test this hypothesis, the KCl-induced increases in [Ca2+]i in
      primarily cultured vascular SMCs exposed to different concentrations of glucose
      were examined. With glucose concentration in solutions kept at 5.5 mM, KCl
      induced a fast increase in [Ca2+]i which then slowly declined (type 1 response)
      in 83% of SMCs from non-diabetic rats. In 9% of non-diabetic SMCs KCl induced a
      slow increase in [Ca2+]i (type 2 response). Interestingly, under the same culture
      conditions KCl induced type 1 and type 2 responses in 47 and 35% of SMCs from
      diabetic rats. When SMCs from non-diabetic or diabetic rats were cultured in 36
      mM glucose, KCl induced a fast increase in [Ca2+]i which, however, maintained at
      a high level (type 3 response). The sustained level of [Ca2+]i in the presence of
      KCl was significantly higher in cells cultured with 36 mM glucose than that in
      non-diabetic cells cultured with 5.5 mM glucose. Furthermore, the hyperglycemia
      induced alterations in calcium mobilization were similarly observed in cells
      cultured in high concentration of mannitol (30.5 mM) or L-glucose, indicating
      that hyperosmolality was mainly responsible for the abnormal calcium mobilization
      in diabetic SMCs.

PMID- 9655182
TI  - Impaired mitochondrial oxidative phosphorylation in skeletal muscle of the
      dystrophin-deficient mdx mouse.
AB  - The mdx mouse, an animal model of the Duchenne muscular dystrophy, was used for
      the investigation of changes in mitochondrial function associated with dystrophin
      deficiency. Enzymatic analysis of skeletal muscle showed an approximately 50%
      decrease in the activity of all respiratory chain-linked enzymes in musculus
      quadriceps of adult mdx mice as compared with controls, while in cardiac muscle
      no difference was observed. The activities of cytosolic and mitochondrial matrix
      enzymes were not significantly different from the control values in both cardiac
      and skeletal muscles. In saponin-permeabilized skeletal muscle fibers of mdx mice
      the maximal rates of mitochondrial respiration were about two times lower than
      those of controls. These changes were also demonstrated on the level of isolated
      mitochondria. Mdx muscle mitochondria had only 60% of maximal respiration
      activities of control mice skeletal muscle mitochondria and contained only about
      60% of hemoproteins of mitochondrial inner membrane. Similar findings were
      observed in a skeletal muscle biopsy of a Duchenne muscular dystrophy patient.
      These data strongly suggest that a specific decrease in the amount of all
      mitochondrial inner membrane enzymes, most probably as result of Ca2+ overload of
      muscle fibers, is the reason for the bioenergetic deficits in dystrophin
      deficient skeletal muscle.

PMID- 9655183
TI  - The mitogen-activated protein kinase pathway contributes to vanadate toxicity in
      vascular smooth muscle cells.
AB  - Vanadate has been considered in the treatment of diabetes because of its insulin
      like effects. However, it has severe toxic effects in both animal and man. In
      cultured cells, vanadate can either cause death or be growth stimulatory,
      depending on the cell type and growth conditions. Here, we report that in baboon
      aortic smooth muscle cells (SMCs), vanadate induced p42/p44 mitogen-activated
      protein kinase (MAPK) activity. This effect was abolished in the presence of the
      specific MAPK kinase (MAPKK) inhibitor PD098059. Although activation of
      p42/p44MAPK/MAPKK is generally thought to be necessary for proliferation, in
      SMCs, vanadate did not promote DNA synthesis and inhibited thymidine
      incorporation stimulated by platelet-derived growth factor (PDGF)-BB in a dose
      dependent fashion (IC50: 30 microM). Prolonged exposure to vanadate exerted
      cytotoxic effects. Cells retracted, rounded up and detached from the substratum.
      These vanadate-induced morphological changes were blocked in the presence of
      PD098059. The addition of PDGF-BB further activated p42/p44MAPK/MAPKK in the
      presence of vanadate and substantially increased vanadate toxicity. We conclude
      from these observations that activation of the p42/p44MAPK/MAPKK signalling
      module contributes to the cytotoxic effects induced by vanadate.

PMID- 9655184
TI  - DNA sequence and muscle-specific expression of human sarcosin transcripts.
AB  - We have characterized two abundant human cDNAs which, through Northern
      hybridization analysis, are selectively expressed in human sarcomeric muscle. DNA
      sequencing was performed and the two cDNAs were found to share sequence identity,
      with the exception of a 3' UTR extension present on the longer transcript. Our
      data suggest that the two transcripts are generated through alternative use of
      two poly(A) addition signals. The cDNAs encode a large open reading frame
      encompassing at least 435 codons. Through sequence comparisons, both at the DNA
      and predicted amino acid sequence level, we have been unable to find significant
      sequence similarity to any other characterized sequence. Consequently, we have
      termed this novel human sequence sarcosin. Although novel, Southern hybridization
      analysis demonstrated that the sarcosin sequence has been conserved in several
      mammalian species.

PMID- 9655185
TI  - Tyrosine kinases and calcium dependent activation of endothelial cell
      phospholipase D by diperoxovanadate.
AB  - Reactive oxygen species (ROS) mediated modulation of signal transduction pathways
      represent an important mechanism of cell injury and barrier dysfunction leading
      to the development of vascular disorders. Towards understanding the role of ROS
      in vascular dysfunction, we investigated the effect of diperoxovanadate (DPV),
      derived from mixing hydrogen peroxide and vanadate, on the activation of
      phospholipase D (PLD) in bovine pulmonary artery endothelial cells (BPAECs).
      Addition of DPV to BPAECs in the presence of .05% butanol resulted in an
      accumulation of [32P] phosphatidylbutanol (PBt) in a dose- and time-dependent
      manner. DPV also caused an increase in tyrosine phosphorylation of several
      protein bands (Mr 20-200 kD), as determined by Western blot analysis with
      antiphosphotyrosine antibodies. The DPV-induced [32P] PBt-accumulation was
      inhibited by putative tyrosine kinase inhibitors such as genistein, herbimycin,
      tyrphostin and by chelation of Ca2+ with either EGTA or BAPTA, however,
      pretreatment of BPAECs with the inhibitor PKC bisindolylmaleimide showed minimal
      inhibition. Also down-regulation of PKC alpha and epsilon, the major isotypes of
      PKC in BPAECs, by TPA (100 nM, 18 h) did not attenuate the DPV-induced PLD
      activation. The effects of putative tyrosine kinase and PKC inhibitors were
      specific as determined by comparing [32P] PBt formation between DPV and TPA. In
      addition to tyrosine kinase inhibitors, antioxidants such as N-acetylcysteine and
      pyrrolidine dithiocarbamate also attenuated DPV-induced protein tyrosine
      phosphorylation and PLD stimulation. These results suggest that oxidation,
      prevented by reduction with thiol compounds, is involved in DPV-dependent protein
      tyrosine phosphorylation and PLD activation.

PMID- 9655186
TI  - Physiological consequences of expression of the Na+/H+ antiporter sod2 in
      Escherichia coli.
AB  - Sod2 is the sodium-proton antiporter on the plasma membrane of the fission yeast
      Schizosaccharomyces pombe. It is vitally important for sodium export and pH
      homeostasis in this organism. Recently, the sod2 gene has been cloned and
      sequenced. However, initial attempts to express sod2 in Escherichia coli using
      the T7 promoter failed. In the present work we examined physiological
      consequences of expression of sod2 in E. coli. To alleviate problems caused by
      expression of sod2 we: (i) used sodium-free media at all steps; (ii) used the
      moderate tac promoter for expression and; (iii) used E. coli strain MH1 which has
      impaired sodium exchange. The effect of sod2 expression on E. coli varied
      depending on the E. coli genotype. When sod2 was expressed in BL21 cells which
      have normal Na+/H+ antiporters, the result was a Li+ sensitive phenotype. LiCl
      completely arrested or prevented growth of BL21 E. coli transformed with the sod2
      gene. The effect on growth was pronounced in media of low external pH. Sod2 was
      then expressed in E. coli MH1 which is devoid of endogenous Na+/H+ antiporters.
      These cells became more resistant to external LiCl, but only in Na+ containing
      media. In the absence of external Na+, the presence of sod2 reduced growth. The
      results are explained in a model which demonstrates the physiological
      consequences of interference by expression of a foreign electroneutral Na+/H+
      antiporter in conjunction with different housekeeping systems of E. coli host
      cells.

PMID- 9655187
TI  - Role of liposomes in selective proliferation of splenic lymphocytes.
AB  - The effects of free and encapsulated allergens of Artemisia scoparia pollen on
      lymphocyte proliferation and immunoglobulin production in BALB/c mice were
      investigated. Splenic lymphocytes from mice immunized with liposome entrapped
      allergen (LEA) elicited a marked proliferative response upon in vitro stimulation
      with both free and encapsulated allergen in comparison to mice immunized with
      free allergen (FA). The serum immunoglobulin profile of mice administered LEA
      revealed a predominance of IgG1 antibodies concomitant with an enhancement of
      IgG2a, IgG2b, IgG3 and IgM responses and suppression of IgE responses. However
      immunization with FA resulted in significant production of IgE responses and low
      levels of IgG antibodies. The differential ability of free and encapsulated
      allergens to selectively induce immunoglobulin isotypes suggests that different
      presentation and T cell differentiation pathways may be followed by FA and LEA in
      the immune system. Proliferation studies involving macrophage depletion
      demonstrated that macrophages play an obligatory role in the processing of LEA.
      Analysis of cytokine production in sera of immunized mice (FA/LEA) revealed that
      LEA induced significant IFN-gamma responses and lower IL-4 responses than mice
      immunized with FA. The results of the present study indicate that liposomes
      synergise the proliferation by the antigen incorporated in it and polarizes the
      response towards Th1 type of cytokine production. The immunoadjuvant and
      immunomodulation property of liposomes make it an efficient vehicle for effective
      immunotherapy.

PMID- 9655188
TI  - In vivo oxidized low density lipoprotein: degree of lipoprotein oxidation does
      not correlate with its atherogenic properties.
AB  - We have recently demonstrated that lipids, particularly cholesterol, covalently
      bound to apolipoprotein B (apoB) are a stable marker of low density lipoprotein
      (LDL) oxidation (Tertov et al. 1995). The present study is an attempt to assess
      the relationship between the degree of LDL oxidation, evaluated by the content of
      apoB-bound cholesterol and the ability of LDL to induce cholesterol accumulation
      in cultured human aortic intimal smooth muscle cells, i.e. LDL atherogenicity.
      Native LDL was oxidized in vitro by copper ions, 2,2-azobis-(2-aminopropane
      hydrochloride), or sodium hypochlorite. Minimum degree of LDL in vitro oxidation
      necessary to convert LDL into atherogenic one was accompanied by an increase of
      apoB-bound cholesterol to the level much higher than that usually observed in
      freshly isolated atherogenic LDL from human blood. Moreover, elimination of LDL
      aggregates from in vitro oxidized LDL preparations by gel filtration led to loss
      of its atherogenic properties. Thus, the ability to induce cholesterol
      accumulation in cells, i.e. the atherogenicity of in vitro oxidized LDL is a
      result of LDL aggregation but not oxidation. We also studied the relationship
      between LDL atherogenicity and apoB-bound cholesterol content in LDL freshly
      isolated from healthy subjects and normo- and hypercholesterolemic patients with
      coronary atherosclerosis. The ability of human LDL to induce cholesterol
      accumulation in aortic smooth muscle cells did not correlate with the degree of
      in vivo LDL oxidation (r = 0.12, n = 90). It is concluded that LDL atherogenicity
      does not depend on the degree of lipid peroxidation in LDL particle.

PMID- 9655189
TI  - Effects of peroxide on endothelial nitric oxide synthase in coronary arteries.
AB  - Reactive oxygen species (ROS) are produced in ischemia and reperfusion. Since
      endothelial nitric oxide synthase (eNOS) is key to the endothelium-dependent
      vasodilation, we examined the effects of peroxide on this enzyme. We treated
      cells cultured from pig coronary artery endothelium with different concentrations
      of hydrogen peroxide, washed them, solubilized them and measured NOS activity by
      arginine to citrulline conversion. Hydrogen peroxide inhibited the eNOS activity
      with an IC50 value of 0.85 +/- 0.39 mM. In another experiment, we perfused
      arteries with solutions containing 0 or 1 mM hydrogen peroxide, washed them,
      removed the endothelium using a cotton swab, centrifuged and solubilized the
      endothelium and monitored its NOS activity. Hydrogen peroxide (1 mM) did not
      affect the NOS activity significantly (p > 0.05) in this assay. We conclude that
      the inactivation of eNOS by hydrogen peroxide does not play a major role in the
      ischemia-reperfusion damage because the peroxide concentrations attained during
      ischemia-perfusion are much lower than those affecting the eNOS activity.

PMID- 9655190
TI  - Biophysical characterization of rat cardiac Ca2+/Mg2+ ecto-ATPase (myoglein).
AB  - Sarcolemmal Ca2+/Mg2+ ecto-ATPase (Myoglein; MW 180 kD) is a membrane bound
      enzyme which requires a millimolar concentration of either Ca2+ or Mg2+ for
      maximal hydrolysis of ATP. The isoelectric point (pI) of the cardiac ecto-ATPase
      was 5.7. The purified Ca2+/Mg2+ ecto-ATPase from the rat heart sarcolemmal
      appeared as a single band with MW approximately 90 kD in the SDS-PAGE. In order
      to understand the nature of this enzyme, the 90 kD band in the SDS-PAGE was
      electroeluted; the analysis of the eluate showed 2 prominent bands with MW
      approximately 90 and 85 kD. The presence of 2 bands was further confirmed by
      gradient gel (10-20%) electrophoresis in 0.375 M Tris-HCl buffer, pH 8.8.
      Analysis of the purified Ca2+/Mg2+ ecto-ATPase as well as the electroeluted
      protein in a non-equilibrium linear two dimensional electrophoresis (Ampholyte pI
      3.0-10.0) also showed two distinct bands. Mass spectroscopic analysis of the
      enzyme using different matrix combinations revealed the presence of multi
      components indicating microheterogeneity in the protein structure. Treatment of
      the ecto-ATPase with DL-dithiothreitol did not alter the pattern of mass
      spectroscopic analysis and this indicated that the microheterogeneity may be due
      to some posttranslational modifications. It is concluded that rat cardiac
      Ca2+/Mg2+ ecto-ATPase is an acidic protein having two subunits. Furthermore, the
      enzyme shows microheterogeneity in its molecular structure.

PMID- 9655191
TI  - Effect of polar glycopeptidolipids from Mycobacterium chelonae (GPLp-Mc) on
      phagocytosis and superoxide anion production of macrophages from mice. Influence
      of physical activity.
AB  - It is not clear how macrophages respond to exercise when the immune system is
      previously activated. The aim of the present work was to determine the response
      of macrophages to exercise in already immunostimulated animals with polar
      glycopeptidolipids extracted from Mycobacterium chelonae (GPLp-Mc). Results
      showed an increased phagocytosis and O2- production in murine macrophages induced
      by the intraperitoneal administration of 25 mg/kg body weight of GPLp-Mc. In
      addition exercise stimulated phagocytic activity and decreased the O2- production
      of these cells. Unexpectedly, exercise did not potentiate the immunostimulatory
      effect of GPLp-Mc. However, we can conclude that the effect of exercise is not
      detrimental to immunostimulated animals.

PMID- 9655192
TI  - Seasonal variation in haematological parameters in male and female Tinca tinca.
AB  - This study was designed to investigate any seasonal (spring, summer, autumn and
      winter) changes in haematological parameters in the blood of Tinca tinca
      measuring the number of red blood cells (RBC), haematocrit, white blood cells,
      and total plasma proteins. The results show significant changes in RBC and
      haematocrit in males comparing spring and summer with autumn and winter, whereas
      in females the RBC remained constant for all 4 seasons but the haematocrit
      decreased in autumn and winter compared to spring and summer. The white blood
      cells of male and female animals were significantly lower in spring and winter
      compared to summer and autumn. In male fish total protein contents significantly
      decreased in autumn and winter compared to spring and summer, whereas in females
      protein output significantly decreased in winter compared to the other seasons.
      The results indicate marked seasonal variation in the blood of male and female
      Tinca tinca. This variation may play a important protective role for the survival
      of the animals.

PMID- 9655193
TI  - The effect of hexadecylphosphocholine on the degradation of mitochondrial
      phospholipids.
AB  - Hexadecylphosphocholine (HePC) is known as antitumor agent but the mechanism has
      not yet been understood. In rat liver mitochondria its effect on phospholipid
      transformation has been studied by quantitative HPTLC and phosphorus
      determination. From the results it can be concluded that HePC influences the
      activities of phospholipase A2, phospholipase C, phospholipase D, and
      lysophospholipase A. The phospholipid transformation as well as the influence of
      HePC are affected by exogenous calcium ions. In the presence of calcium HePC has
      been found to inhibit enzyme activities, whereas in the absence of exogenous
      calcium ions enzymatic phospholipid transformations are activated or inhibited
      depending on HePC concentrations.

PMID- 9655194
TI  - Stimulation by hexose esters of lactate production by rat erythrocytes:
      insensitivity to 3-O-methyl-D-glucose and inhibition by 2-deoxy-D-glucose and its
      tetraacetic ester.
AB  - Selected esters of D-glucose were recently proposed as tools to provide the sugar
      to cells, whilst bypassing the carrier system for hexose transport across the
      plasma membrane. In the present study, alpha-D-glucose pentaacetate, beta-D
      glucose pentaacetate, alpha-D-mannose pentaacetate and, to a lesser extent, 6-O
      acetyl-D-glucose, all tested at a 1.7 mM concentration, were found to increase
      lactate production above basal value in rat erythrocytes. Over 90 min incubation,
      the increment in lactate production ranged from about 1.2 (alpha-D-glucose
      pentaacetate) to 0.6 (6-O-acetyl-D-glucose) micromol/microl of erythrocytes.
      Little or no change in lactate production was observed in cells exposed to beta-L
      glucose pentaacetate, alpha-D-glucose pentaethylsuccinate, alpha-D-galactose
      pentaacetate or beta-D-galactose pentaacetate. The metabolic response to alpha-D
      glucose pentaacetate was resistant to 3-O-methyl-D-glucose (10-80 mM) which
      suppressed, however, that evoked by D-glucose. D-mannoheptulose (10 mM) virtually
      failed to affect the response to D-glucose and its pentaacetate ester. On the
      contrary, 2-deoxy-D-glucose (10.6 mM) inhibited to the same relative extent (55%
      decrease) lactate production in erythrocytes exposed to either unesterified D
      glucose or alpha-D-glucose pentaacetate. The tetraacetic ester of 2-deoxy-D
      glucose was more efficient than unesterified 2-deoxy-D-glucose in inhibiting
      lactate production from alpha-D-glucose pentaacetate. It is proposed that
      selected esters of saccharides represent useful tools to bypass defects in hexose
      transport, and to increase their nutritional or therapeutic efficiency.

PMID- 9655195
TI  - Ca2+/calmodulin dependent protein kinase from Mycobacterium smegmatis ATCC 607.
AB  - A soluble Ca2+/calmodulin dependent protein kinase has been partially purified
      (approximately 400 fold) from Mycobacterium smegmatis ATCC 607 using several
      purification steps like ammonium sulphate precipitation (30-60%), Sepharose CL-6B
      gel filtration, DEAE-cellulose and finally calmodulin-agarose affinity
      chromatography. On SDS-PAGE, this enzyme preparation showed a major protein band
      of molecular mass 35 kD and its activity was dependent on calcium, calmodulin and
      ATP when measured under saturating histone IIs (exogenous substrate)
      concentration. Phosphorylation of histone IIs was inhibited by W-7 (calmodulin
      inhibitor) and KN-62 (CaM-kinase inhibitor) with IC50 of 1.5 and 0.25 microm
      respectively, but was not affected by inhibitors of PKA (Sigma P5015) and PKC (H
      7). All these results confirm that purified enzyme is Ca2+/calmodulin dependent
      protein kinase of M. smegmatis. The protein kinase of M. smegmatis demonstrated a
      narrow substrate specificity for both exogenous as well as endogenous substrates.
      These results suggest that purified CaM-kinase must be involved in regulating
      specific function(s) in this organism.

PMID- 9655196
TI  - Insulin-induced Glut4 recruitment in the fatty Zucker rat heart is not associated
      with changes in Glut4 content in the intracellular membrane.
AB  - Impaired cardiac glucose metabolism and glucose transport have been shown in the
      insulin resistant fatty Zucker rat. The aim of the present study was to examine
      the translocation of the insulin-sensitive glucose transporter (Glut4) in the
      heart of the fatty Zucker rat under in vivo conditions. Insulin was injected into
      both lean (FA/?) and fatty (fa/fa) Zucker rats via the tail vein. The time course
      of cardiac Glut4 translocation was studied by determining the subcellular
      distribution of Glut4 using a newly developed ELISA quantitation method. Insulin
      (10 U/kg) caused a 30% and 37% increase in plasma membrane Glut4 content at 20
      min after injection in lean and fatty rats respectively. The plasma membrane
      Glut4 contents in the basal and insulin-stimulated states were significantly
      lower in the fatty rat when compared to the lean control. The dose effect of
      insulin (2.5-10 U/kg) on Glut4 mobilization to the plasma membrane was similar in
      both phenotypes. The time course of Glut4 mobilization to the plasma membrane (5
      30 min), which was similar in both lean and fatty Zucker rats, showed that
      maximal translocation was reached at 5 min post insulin injection and persisted
      throughout the remaining 25 min. However, in fatty Zucker rats, Glut4 content in
      the intracellular membrane remained unchanged at all insulin doses and all time
      points studied. Collectively, these results show that Glut4 recruitment to the
      plasma membrane is responsive to insulin in the fatty Zucker rat heart and that
      the maximal response was similar to that in lean Zucker rats. However, the
      recruitment of Glut4 to the plasma membrane was not associated with changes in
      the intracellular membrane Glut4 content.

PMID- 9655197
TI  - Phosphorylation of stathmin modulates its function as a microtubule
      depolymerizing factor.
AB  - Oncoprotein 18 or stathmin was isolated from bovine brain, characterized and
      novel features of its function as a microtubule depolymerizing factor were
      tested. The effect of phosphorylation of stathmin on its function as a
      microtubule depolymerizing factor has been tested in vitro. Five different
      protein kinases, protein kinase A, MAP kinase, cdc2 kinase, glycogen synthase
      kinase 3 and casein kinase 2, were used to modify stathmin, since it is known
      that these kinases could phosphorylate several residues that are modified in vivo
      and could have important roles in stathmin function. The residues phosphorylated
      in vitro by the different protein kinases were identified and in some cases they
      correspond to those modified in vivo. Recombinant unphosphorylated stathmin and
      native stathmin, which was previously dephosphorylated with alkaline phosphatase,
      showed similar microtubule depolymerizing activity. This activity is higher than
      that of stathmin phosphorylated by protein kinase A, MAP kinase or cdc 2 kinase,
      whereas phosphorylation of the protein with casein kinase 2 or glycogen synthase
      kinase 3 resulted in a slight increase of the depolymerizing activity.

PMID- 9655198
TI  - Erythrocytes from healthy smokers bind more bilirubin than the erythrocytes from
      healthy non-smokers.
AB  - Cigarette smoking is an adverse prognostic factor for health. Its damaging
      effects on many enzymatic and cellular activities are well known. The present
      study was carried out to evaluate whether there is a difference in the binding of
      bilirubin to the erythrocytes from healthy smokers and non-smokers. The results
      suggest that the binding of bilirubin to the erythrocytes from healthy smokers as
      well as in vitro smoked erythrocytes is significantly higher than that of healthy
      non-smokers.

PMID- 9655199
TI  - Depletion of endogenous dopamine stores and shift in beta-adrenoceptor subtypes
      in cardiac tissue following five weeks of chronic denervation.
AB  - Surgical ablation of extrinsic cardiac nerve fibers results in a chronically
      denervated state of the left ventricle of the heart. The present study was
      performed to elucidate the effect of a period of 5 weeks of chronic denervation
      on cardiac catecholamine levels in general and dopamine in particular. Moreover,
      the possible effect on cardiac beta-adrenoceptor subtypes was investigated.
      Experiments were performed on adult dogs. In addition to adrenaline and
      noradrenaline the tissue levels of dopamine were found to be severely depressed.
      A significant shift from beta1- to beta2-adrenoceptor subtype was observed, while
      the total beta-adrenoceptor density remained unaffected. The present findings
      indicate that catecholamine synthesis in chronically denervated hearts is
      impaired upstream of dopamine and that a shift in beta-adrenoceptor subtype
      occurs already within a relatively short period of five weeks of denervation, and
      suggest that the lack of endogenous catecholamines influence the relative
      expression levels of the two subtypes of beta-adrenoceptors present in cardiac
      tissue.

PMID- 9655200
TI  - Postural control in benign paroxysmal positional vertigo before and after
      recovery.
AB  - Thirty-two patients affected by idiopathic benign paroxysmal positional vertigo
      (BPPV) of the posterior semicircular canal were studied before, 3 days and I
      month after a resolutive Semont manoeuvre by means of dynamic posturography. The
      overall postural control in BPPV patients was shown to be impaired, as
      demonstrated by the pathological equilibrium scores. Data obtained before
      treatment showed a specific pattern of vestibular involvement and a pathological
      composite score. After the liberatory manoeuvre the Sensory Organization Test
      indicated a significant improvement in the pathological composite and vestibular
      scores. However, significant differences from controls were still detected 3 days
      and 1 month after clinical recovery from BPPV. The results clearly show that, in
      BPPV patients, there is an impairment of the vestibular system, which seems
      unable to maintain a normal postural balance. This deficit can be particularly
      detected when dynamic posturography evaluates the vestibular cues. After the
      liberatory manoeuvre a consistent improvement in the overall postural control has
      been observed but the residual differences from controls seem to suggest that
      damage to the otoconial maculae influences postural control, even when there is
      significant improvement in the clinical signs.

PMID- 9655201
TI  - Intratympanic gentamicin in Meniere's disease.
AB  - Ninety-three patients with intractable Meniere's disease were treated with
      gentamicin (Garamycin 40 mg/ml) administered in 1 to 4 transtympanic injections.
      The patients were tested at frequent intervals and followed up for 2 years.
      Before treatment all subjects experienced moderate or severe handicap caused by
      Meniere's disease. Two years after the treatment, rotatory vertigo was abolished
      in 81% of subjects, Tumarkin attacks were cured in 60%, and work capacity was
      severely reduced in 10% and moderately reduced in 17% of subjects. The outcome of
      the caloric responses did not correlate with the outcome of the treatment. In
      logistic regression analysis poor outcome of treatment correlated with Tumarkin
      attacks (odds ratio 5.5), severity of vertigo (odds ratio 3.8) and gait disorders
      (odds ratio 2.9). The mean hearing level was significantly affected by the
      treatment (before, 59.1 dB HL; after, 67.9 dB HL). Ten treated ears became
      deafened. During follow-up 44 subjects were subjected to retreatment, usually
      after 6 months. Intratympanic gentamicin treatment is a relatively safe and
      effective way to treat Meniere's disease. The authors recommended starting with 2
      injections and renewing the injections if relapse occurs.

PMID- 9655202
TI  - The subjective visual horizontal after stapedotomy: evidence for an increased
      resting activity in otolithic afferents.
AB  - The subjective visual horizontal (SVH) was measured by means of a small rotatable
      luminous line in darkness in the upright body position and at 10, 20 and 30
      degrees of body tilt to the right and left prior to, and during a follow-up
      period after, stapedotomy in 12 patients with otosclerosis. In the acute stage
      after surgery, SVH in the upright body position was significantly tilted away
      from the operated side. In addition, the perception of roll tilt towards the
      operated side (Kop) was significantly increased after stapedotomy, while the
      perception of roll tilt towards the healthy side (Khe) showed a slight but not
      significant reduction. After exclusion of two outliers, a statistically
      significant correlation was found between changes in Kop and in Khe. The slope of
      the regression line was 1.8:1, probably corresponding to a preference of the
      utricle for ipsilateral as opposed to contralateral head tilt. In four patients
      there was a weak ( < 1 degrees/s) spontaneous nystagmus, not systematically
      related to the side of surgery, while in most cases there were no nystagmus or
      subjective vertigo symptoms. These specific changes in the subjective horizontal
      show that the otolithic effects on perception can be dissociated from canal
      effects. Further, the results are opposite to those for patients with unilateral
      loss of vestibular function. The tilt of SVH after stapedotomy indicates an
      increase in resting activity of utricular afferents. In addition, based on recent
      theories on otolith function, we suggest that an increased activity in saccular
      afferents is of major importance for the changes in roll-tilt perception because
      of its interaction with the utricle on the central nervous level.

PMID- 9655203
TI  - Effect of probe frequency and gender on click-evoked ipsilateral acoustic reflex
      thresholds.
AB  - This study was designed to evaluate the effects of gender and probe frequency on
      the ipsilateral click-evoked acoustic reflex thresholds. Ipsilateral acoustic
      reflex thresholds were obtained from the left ear of each subject (12 male and 12
      female normal young adults) by presenting clicks at the rate of 180/sec. The
      probe tone frequencies were 226, 678 and 1.000 Hz. The results revealed that
      acoustic reflex thresholds for the 678 Hz probe were significantly higher than
      those obtained with the 226 and 1.000 Hz probes. No gender differences were
      apparent. However, the static admittance was significantly correlated with the
      acoustic reflex thresholds for the 678 Hz probe in only the female subjects. For
      the 226 Hz probe, the elicitation of the reflex resulted in a decrease in static
      admittance in all the subjects. For the 678 Hz probe, the admittance decreased in
      58% of the subjects and it increased in 42% of the subjects. For the 1,000 Hz
      probe, an increase in admittance was apparent in all of the subjects. The results
      suggest that either the 226 Hz or the 1,000 Hz probes can be used for the
      measurement of click-evoked acoustic reflex thresholds in adults.

PMID- 9655204
TI  - Intracochlear factors contributing to psychophysical percepts following cochlear
      implantation.
AB  - The performance of cochlear implant patients may be related to intracochlear,
      histopathological factors. We have performed detailed post-mortem examinations of
      five human, implanted cochleas and for each electrode correlated the
      psychophysical threshold, comfortable level and dynamic range with spiral
      ganglion cell survival, presence of fibrous tissue and/or new bone, and distance
      between the centers of the electrode bands and Rosenthal's canal. The
      psychophysical parameters were strongly interrelated. Threshold and comfort
      levels correlated with the distance between the electrodes and Rosenthal's canal.
      Threshold levels also correlated with the presence of intracochlear fibrous
      tissue and new bone, especially with the former. The dynamic range showed a
      negative correlation with intracochlear pathology, especially with new bone.
      Comfort levels and dynamic range were related to spiral ganglion cell survival.
      The distance between the electrodes and the modiolus increased with increasing
      levels of fibrous tissue and new bone. Spiral ganglion cell survival was
      decreased with increasing levels of fibrous tissue and new bone.

PMID- 9655205
TI  - Acoustic neuroma/vestibular schwannoma growth: past, present and future.
AB  - The growth of vestibular schwannoma (VS) was investigated in a series of 123
      patients with 127 tumors in the period 1973 1993. The material was reanalysed and
      updated 3 years later in 1996. By termination of the first observation period
      (mean 3.4 years), 94 tumors (74%) exhibited measurable growth, 23 tumors (18%) no
      measurable growth and 10 tumors (8%) negative growth. By the end of the extended
      observation period (mean 3.8 years), tumor growth was observed in 104 tumors
      (82%), no tumor growth in 15 tumors (12%) and negative growth in eight tumors
      (6%). Several growth patterns were noticed: however, these were not static as the
      growth patterns of the tumors changed during the extended observation period.
      Accordingly, the expected growth figures by the end of this century (mean
      observation period approximately 4 years) will probably be: growth in 111 tumors
      (87%), no growth in 10 tumors (8%) and negative growth in six tumors (5%). The
      results indicate that neither the present study nor the previously published
      studies on tumor growth reflect the natural history of VS, but they only provide
      information on tumor growth, growth rates and growth patterns during a given
      observation period.

PMID- 9655206
TI  - The endolymphatic sac receives antigenetic information from the organs of the
      mucosa-associated lymphatic system.
AB  - The endolymphatic sac holds the entire arrangement of immunocompetent cells and
      functions as an immunological potent control organ for the inner ear. The
      evidence of secretory immunoglobulin A and other features of lymphocyte subtypes
      characterizes the endolymphatic sac as an organ of the mucosa-associated
      lymphatic system (MALT). In this system a permanent recirculation of sensitized
      memory lymphocytes from one organ to the other has been demonstrated
      experimentally as serving to dispose memory lymphocytes after renewed antigenetic
      stimulus. The aim of this study was to prove the possible recirculation of
      antigen-sensitized lymphocytes to the endolymphatic sac after antigenic stimulus
      of another part of the mucosa-associated lymphatic system. The results are
      evidence that the endolymphatic sac is provided with immunocompetent cells which
      derive from the lymphatic tissue of the nasopharynx. While the origin of
      immunocompetent cells in the endolymphatic sac still remains uncertain, this
      study underlines the role of lympho-epithelial tissue of the nasopharynx as a
      possible cell source for the endolymphatic sac. The results might explain the
      altered or disturbed function of the endolymphatic sac as a possible cause of
      certain inner ear diseases.

PMID- 9655207
TI  - Effects of transforming growth factor-beta1 and basic fibroblast growth factor on
      proliferation of cell cultures derived from human vestibular nerve schwannoma.
AB  - The influence of transforming growth factor-beta1 (TGF-beta1) and basic
      fibroblast growth factor (bFGF) on growth of cell cultures derived from
      unilateral vestibular nerve schwannomas was investigated. Cell cultures were
      initiated from 9 schwannomas and characterized immunocytochemically with
      antibodies against S-100 and type IV collagen. The effects of TGF-beta1 and bFGF
      on DNA synthesis in chemically defined serum-free medium were assessed by
      measuring the incorporation of 5-bromo-2'-deoxy-uridine (BRDU) into cellular DNA.
      Cell proliferation was evaluated with an electronic cell counter. Reverse
      transcription polymerase chain reaction (RT-PCR) was performed using
      oligonucleotide primers specific for TGF-beta1 and TGF-beta2. TGF-beta1
      stimulated DNA synthesis in a dose dependent manner. Maximal stimulation was
      observed at a concentration of 1 ng/ml, which induced a nearly 2-fold increase in
      DNA content. This effect was not seen when TGF-beta1 was added in the presence of
      neutralizing antibodies. In addition, antibodies against TGF-beta1 significantly
      reduced DNA synthesis in control cultures without supplemented exogenous growth
      factors. bFGF alone had no significant effects on DNA synthesis. In contrast,
      when TGF-beta1 and bFGF were added together, the mitogenic response was much
      greater than produced by TGF-beta1 alone. RT-PCR showed that the cultured cells
      expressed mRNA for both TGF-beta1 and TGF-beta2. We hypothesize that TGF-beta1 is
      an autocrine growth factor for human vestibular nerve schwannomas in culture. A
      similar mechanism might be involved in the growth of these tumors in situ.

PMID- 9655208
TI  - Perikaryal myelination of cultured chick embryo statoacoustic ganglion cells: an
      electron microscopic study.
AB  - Perikaryal myelin formation on cultured chick embryo statoacoustic ganglion (SAG)
      cells was studied using electron microscopy. SAGs were dissected from 13-day
      embryos and cultured for 1 to 6 weeks. Myelinated perikarya, which were
      completely encircled by two or more layers of loose and/or compact myelin
      lamellae like those in vivo in the chick, were first observed in 3-week-cultured
      SAGs; myelinated axons appeared in 2-week-cultured SAGs. The perikaryal
      myelination progressively increased loose and compact lamellae and the axonal
      myelination increased compact lamellae. In 4- to 6-week-cultured SAGs, 11 to 12%
      of SAG cells had the myelinated perikaryon of which perikaryal myelin lamellae
      terminated at the axon hillock in the same manner as those in vivo in the chick.
      The number of layers of myelin lamellae around the myelinated perikaryon in 5- to
      6-week-cultured SAGs and around the myelinated axon in 4- to 6-week-cultured SAGs
      ranged between 2 and 15, and between 12 and 26, respectively. Since these numbers
      were consistent with those in vivo in chicks 3 days after hatching, it is
      suggested that the culture provides perikaryal myelin sheaths, which are
      equivalent to those in vivo in structure, in more than 10% of SAG cells, while
      the myelination process in vitro is carried out much more slowly than that in
      vivo.

PMID- 9655209
TI  - An in vitro model for acoustic overstimulation.
AB  - Although many studies have been performed on the effects of acoustic
      overstimulation on the inner ear, our knowledge about the cellular processes
      underlying reduced hearing sensitivity and auditory cell death is still limited.
      In order to further our understanding of cellular processes occurring in
      conjunction with acoustic trauma, we designed an in vitro model to study the
      effects of overstimulation directly on sensory hair cells isolated from the low
      frequency part of the guinea pig cochlea. The isolated outer hair cells were
      subjected to pressure jets delivered by a glass micropipette positioned close to
      the cell, in order to mimic the pressure changes occurring in the intact inner
      ear during sound stimulation. A second micropipette coupled to a piezoresistive
      pressure transducer was used as a probe measuring the pressure at precise
      locations at and around the cell. In a previous study, we found that such
      stimulation gave rise to increases in the intracellular calcium concentration.
      The present study characterizes the stimulus, describes the computer-controlled
      setup used for calibration, and gives examples of different modes of
      overstimulation at the cellular level. The peak pressure that could be generated
      using the pressure jet was around 325 Pa, or 144 dB (re 20 microPa) at 140 Hz.
      The pressure jet elicited large mechanical vibrations of the cell bodies of
      isolated cells. The vibration mode of the cells often changed over time, implying
      that the stimulation caused changes of the cellular stiffness. However, most
      cells appeared quite resistant to the high intensity mechanical stimulation.

PMID- 9655210
TI  - Experimental study on the effects of gentamicin injection on the guinea-pig:
      electrophysiological studies.
AB  - The inner ear distortion induced by gentamicin (GM), a type of aminoglycoside
      antibiotic, was examined in guinea-pigs. Previous studies which investigated the
      function of the eighth cranial nerve and organ of Corti using cochlear
      microphonics (CM) and compound action potential (CAP) reported ototoxicity
      following experimental exposure to GM. In this report, the effects of GM on the
      cochlea and the eighth cranial nerve were investigated systematically by
      measuring CM, CAP, summating potentials induced by 90 dB (SPL) tone burst,
      endocochlear potential (EP) and K+ ion concentration of the endolymph. Guinea
      pigs were treated with a daily intramuscular injection of GM (60 mg in 1.5 cc) at
      a dose of 60 mg/kg during different treatment periods. The maximum output voltage
      of AP was decreased by injection of GM (60 mg/kg x 24). A decrease in the CM
      maximum output voltage and the elevation of CM pseudothreshold were typically
      seen after GM injection at a test frequency of 8 kHz and a decrease in CAP was
      also observed. Changes in EP during 3 min anoxia were observed, in particular a
      decrease in the absolute value of the negative potential. The endolymph K+ ion
      concentration remained unchanged. These findings indicate that the diffusion
      potentials decreased at the same time as reduction of maximum output voltage in
      CM induced by GM injection.

PMID- 9655211
TI  - Continuous long-term measurements of the middle ear pressure in subjects without
      a history of ear disease.
AB  - A new method was used for continuous measurement of the middle ear (ME) pressure
      during a 24-h period. In 10 subjects without a history of ear disease a small
      perforation was made through the tympanic membrane. A tight rubber stopper
      containing a small polyethylene tube was fitted into the external ear canal.
      Conventional tubal function tests were performed. The equipment was then carried
      by the subjects for 24 h of normal activity to monitor any slow or rapid dynamic
      pressure change in the ME. Body position was found to be the most important
      factor affecting ME pressure variation, during the 24-h continuous pressure
      measurements. A significant pressure rise occurred in the recumbent position in
      all but one subject. Few rapid pressure equilibrations were seen during the
      recordings, indicating few tubal openings. This implies that the pressure changes
      in the ME seen in this study were mainly the result of gas exchange over the
      mucosa. The investigation might be a base for reference when investigating
      different kinds of pathologic conditions in the ear.

PMID- 9655212
TI  - Elevated autoantibodies in sera from otosclerotic patients are related to the
      disease duration.
AB  - In this study an indirect ELISA with patients' sera was performed using human
      collagen type II, double- (dsDNA) and single-stranded DNA (ssDNA), thyroid
      microsomal antigen, insulin and lysozyme as antigens. Since many preoperated
      otosclerotic patients demonstrated the signs of myringosclerosis (n=7). they were
      classified separately and compared with otosclerotic patients without
      myringosclerosis (n=28), with healthy controls (n=42) and with patients with
      tympanosclerosis (n=5) of other origin. The otosclerotic patients had serum
      antibodies to antigens tested similar to normal controls. However, elevated
      antibody levels to human collagen type II, dsDNA and ssDNA were observed only in
      patients with a disease duration between 3 and 5 years as compared to other
      otosclerotic patients. The same duration association was observed in the level of
      the total serum alkaline phosphatase activity. These observations would suggest
      that the enzymatic bone resorption is the driving force in human otosclerosis.
      Elevated serum autoantibodies during tissue reparation in the otosclerotic stage
      may be a transient response to sustained excess antigen turnover in the primary
      lesion.

PMID- 9655213
TI  - Ribotyping of strains of Moraxella (Branhamella) catarrhalis cultured from the
      nasopharynx and middle ear of children with otitis media.
AB  - Moraxella (Branhaomella) catarrhalis is frequently present in the nasopharyngeal
      microflora of small children, especially during episodes of acute otitis media .
      By means of ribotyping (restriction endonuclease analysis of chromosomal DNA
      combined with rRNA probing), we studied the genetic heterogeneity of 78 cultures
      of M. catarrhalis obtained from different localities in the nasopharynx of nine
      young children with secretory otitis media. Using HindIII and PstI as
      endonucleases, five different ribotypes were recognized, representing at least
      five different genotypes of M. catarrhalis. The distribution of these types was
      found to be almost identical to the distribution among 16 M. catarrhalis strains
      cultured from middle ear exudates of 16 children with acute otitis media.
      Ribotype HAPA was found in two-thirds of all the cultures investigated, and 44%
      of the children harboured more than one ribotype in the nasopharynx at the same
      time. The vast majority of the nasopharyngeal M. catarrhalis cultures were beta
      lactamase positive. One child had both a HAPA ribotype, beta-lactamase-negative
      strain in the nasopharyngeal secretions, and HAPA ribotype, beta-lactamase
      positive strains at the entrance of the eustachian tube, the nasopharyngeal
      tonsils, the folds of the nasopharyngeal tonsils and the oropharynx. All except
      one of the M. catarrhalis strains cultured from middle ear exudates were beta
      lactamase positive.

PMID- 9655214
TI  - Different production of interleukin-1alpha, interleukin-1beta and interleukin-8
      from cholesteatomatous and normal epithelium.
AB  - Cholesteatomatous bone destruction is caused by an increase in collagenase
      activity and activation of the osteoclasts. Cytokines. such as interleukins (IL),
      are important in intercellular communication in the mechanism of bone
      destruction. Middle ear cholesteatomas and external auditory canal skins (EACS)
      can be surgically obtained and cultured. The quantities of IL-1alpha, IL-1beta
      and IL-8 secretions were measured in the supernatant of each culture series. On
      the 2nd day of culture, the level of IL-1alpha was 0.60+/-0.13 (pg/microg of
      total protein) in cholesteatoma, and 0.25+/-0.02 in EACS. The levels of IL-1beta
      in cholesteatoma and EACS were 0.41+/-0.06 and 0.24+/-0.02, respectively. The
      levels of IL-8 in cholesteatoma and EACS were 146.50+/-32.37 and 50.40+/-6.24,
      respectively. After 2 days, the levels of IL-1alpha and IL-8 of each tissue
      decreased. The value from fibroblasts did not show a significant difference
      between cholesteatoma and EACS, and the values did not change as time passed. We
      can conclude that the IL-1alpha and IL-8 from the cholesteatomatous epithelium
      are responsible for the cholesteatomatous bone destruction and certain substances
      from the subepithelial granulation tissue can stimulate the cholesteatoma to
      produce IL-1alpha and IL-8.

PMID- 9655215
TI  - Late phase response in nasal mucosa closely correlated with immediate phase
      reaction and hyperreactivity to histamine.
AB  - It has been suggested that the onset of the late phase response (LPR) and
      hyperreactivity to non-specific stimuli occurs in the lower airway. However, its
      relationship in the nose has not yet been studied. This study was designed to
      examine the mechanism of LPR and the relationship between LPR and
      hyperreactivity. A total of 25 Japanese cedar pollinosis patients participated in
      this study. On the first visit, the frequency of sneezes, weight of nasal
      discharge, and the nasal airway resistance (NAR) were time-dependently measured
      without antigen challenge. The histamine reactivity was observed after 12 h. The
      same protocol was used during the second to fourth visits. The frequency of
      sneezes, weight of nasal discharge, and NAR were measured continuously for 12 h
      after antigen challenge, and nasal reactivity to histamine was observed. The
      percent change of NAR during immediate phase response (IR) and during LPR showed
      a significant correlation. The frequency of sneezes and weight of nasal discharge
      induced by histamine were both significantly higher in the positive than in the
      negative LPR group. These results suggest that the chemical mediators and
      inflammatory cells inducing nasal swelling during IR cause, directly or
      indirectly, nasal swelling during LPR, and induce hyperreactivity to histamine.

PMID- 9655216
TI  - Distribution and quantity of neuroendocrine markers in allergic rhinitis.
AB  - Neuroendocrine components exist in the human nasal mucosa. However, the
      pathophysiological and neuroimmunological roles of the regulatory peptides in
      allergic rhinitis (AR) require further investigation. To analyse the functional
      morphology and quantify the tissue concentration of regulatory peptides in the
      nasal mucosa of AR subjects, human inferior turbinate mucosa specimens from 25
      patients with AR, 20 patients with non-allergic rhinitis and 10 patients without
      any nasal diseases were investigated. Using immunohistochemistry and
      radioimmunoassays, we detected the presence, distribution and concentrations of
      various neuropeptides [vasoactive intestinal peptide (VIP), neuropeptide Y (NPY),
      substance P (SP) and calcitonin gene-related peptide (CGRP)] and general
      neuroendocrine markers (neuron-specific enolase and chromogranin A). Quantitative
      analysis of the stained fibres and cells was performed using a graphic AutoCAD
      program. The presence and distribution of NPY, CGRP and SP nerve fibres and
      neuroendocrine cells were similar among the three subject groups. AR subjects had
      significantly higher tissue concentrations of VIP and SP. AR subjects had
      increased numbers of VIP fibres which predominantly innervated vessels. Thus, VIP
      and SP play important neuroimmunological roles in the pathogenesis of AR.

PMID- 9655217
TI  - Expression of intercellular adhesion molecule-1 on the vascular endothelium in
      nasal polyps before, during and after topical glucocorticoid treatment.
AB  - Nasal polyposis is a result of a chronic inflammatory disorder in the upper
      airways. In vitro studies have revealed that extravasation of leucocytes requires
      interactions between several sets of adhesion molecules expressed on the
      circulating leucocytes and the vascular endothelium. Therefore, the endothelial
      expression of intercellular adhesion molecule-1 (ICAM-1) in biopsies from polyps
      and inferior turbinates was investigated by the use of immunohistochemical
      staining. Biopsies were obtained from 11 patients suffering from nasal polyposis
      before, during and after treatment with 100 microg budesonide (Rhinocort
      Turbuhaler) in each nostril twice daily. Before, during and after treatment, ICAM
      1 was expressed in the majority of vessels in polyps and mucosa of inferior
      turbinates. The intensity of endothelial ICAM-1 expression in polyps was
      significantly reduced during topical glucocorticoid treatment compared with the
      pretreatment and posttreatment levels (p < 0.005). In biopsies from the inferior
      turbinates, the intensity of the endothelial ICAM-1 expression was lower during
      treatment than after discontinuation of medical treatment (p < 0.005). In
      conclusion, topical budesonide treatment seems to downregulate ICAM-1 expression
      on the vascular endothelium in nasal polyps. Such an effect may interfere with
      leucocyte extravasation and partially account for the anti-inflammatory effect of
      local glucocorticoid treatment in human nasal polyposis.

PMID- 9655218
TI  - The vomeronasal (Jacobson's) organ in adult humans: frequency of occurrence and
      enzymatic study.
AB  - The vomeronasal system in adult humans has commonly been regarded as absent or
      vestigial, but recently it was found to be more common than previously reported.
      In this study, a search for the frequency of occurrence of the vomeronasal organ
      (VNO) was performed by examining the nasal septae of 200 adult patients. The
      frequency of occurrence was found to vary according to the method of examination.
      By anterior rhinoscopy, large pits and even deep grooves lined by glistening
      mucosa were visible in 16% of the people examined. Using nasal endoscopes this
      ratio increased to 76%. After receiving informed, written consent, from 13
      patients undergoing endonasal surgery under general anaesthesia, one VNO was
      dissected out. Specimens were examined histologically and histochemically for
      succinic dehydrogenase and alkaline phosphatase enzymes. One specimen was
      processed for transmission electron microscopy. Two morphologically distinct cell
      types were differentiated. One cell type was previously suggested to have some of
      the features associated with nerve cells and could have a sensory function. A
      possible function for the VNO is postulated.

PMID- 9655219
TI  - Evaluation of the vascular reaction in pharyngeal mucosa.
AB  - The patency of the upper airways during inspiration is maintained by reflexogenic
      muscular dilation, mediated by afferent nerves. Our hypothesis is that a local
      disturbance in these nerves might explain the increased tendency of upper airways
      to collapse in patients with obstructive sleep apnea. The vascular reaction in
      the mucosal microcirculation is regulated by afferent nerves. To investigate
      this, we developed the laser Doppler perfusion monitoring method and electrical
      nerve stimulation for investigations of the soft palatal mucosa in non-snoring
      subjects. A 12 cm probe with integrated bipolar electrodes and a special probe
      holder were designed. The bandwidths 12 and 24 kHz were compared and the latter
      was better able to detect a high blood-flow. A dose response relation was found
      between the voltage stimulation level and percentage increase in blood-flow.
      Three series of stimuli (40 V) in 10 subjects caused reproducible vascular
      reactions. In conclusion, this method seems to be safe, tolerable and valuable
      for investigations of patients with obstructive sleep apnea or other pharyngeal
      disorders, e.g. dysphagia, in the search for local nerve lesions.

PMID- 9655220
TI  - The free radical forearm flap: a reliable method for reconstruction of the
      laryngohypopharynx after in-continuity resection.
AB  - Between 1992 and 1996 14 patients with a squamous cell carcinoma of the
      laryngohypopharynx underwent tumour resection and primary reconstruction with the
      free volar forearm flap. Tumour resection was performed by a head and neck
      surgeon and reconstruction by a plastic surgeon. Preoperative radiotherapy was
      given to 13 patients and postoperative radiation to one patient. Thirteen
      patients were male and one patient was female, with a mean age of 66 years (range
      53-79 years). The flap was harvested from the left forearm in 12 cases and from
      the right in two. The mean operation time was 12 h (range 11-20 h), and the mean
      intraoperative bleeding volume was 700 ml (range 400-1,000 ml). Twelve of 14
      flaps survived. One flap was totally lost 3 weeks postoperatively and another was
      partially lost 2 weeks after surgery. Overall revisional surgery was carried out
      in six patients. Infections and fistulae at the neck occurred in six of the 14
      patients. Six of the 14 patients were alive at follow-up. One patient died of an
      acute haemorrhage from an oesophageal ulcer 2 months after surgery, one patient
      died of a second primary oesophageal cancer and six patients developed
      recurrences. The mean survival time was 26 months (range 2-43 months).

PMID- 9655221
TI  - Non-radioactive semiquantitative testing for the expression levels of telomerase
      activity in head and neck squamous cell carcinomas may be indicative for
      biological tumour behaviour.
AB  - Head and neck cancer arises and progresses through specific genetic alterations
      which lead to an invasive immortal phenotype. The process of immortalization is
      associated with the activation of the enzyme telomerase, a ribonucleoprotein with
      reverse transcriptase activity which is capable of synthesizing telomeric repeats
      at the end of chromosomes. This enzyme is expressed in nearly all neoplasms and
      germline cells and is absent in most normal human somatic cells. Because of this
      expression pattern testing for telomerase activity may deliver useful diagnostic
      and/or prognostic information about clinical tumour behaviour. Telomerase
      activity was therefore analysed in 16 primary lesions of head and neck squamous
      cell carcinomas (HNSCC) using the polymerase chain reaction-based telomeric
      repeat amplification protocol (TRAP). For a sensitive semiquantitative analysis
      of telomerase activity TRAP products were mixed with Pico Green I and the
      fluorescence emission intensities were measured. All 16 samples tested positive.
      When the Pico Green I data were compared with clinical parameters, it was obvious
      that N0 necks revealed significantly (p < 0.05) lower emission intensities (i.e.
      telomerase activity) than N + necks. Our results indicate that a high telomerase
      activity in HNSCC may facilitate lymph node metastasis and that the estimation of
      telomerase activity is a useful diagnostic tool which could influence treatment
      modalities.

PMID- 9655222
TI  - Correlation of epidermal growth factor receptor and radiosensitivity in human
      maxillary carcinoma cell lines.
AB  - To determine the relationship between epidermal growth factor receptor (EGFR) and
      radiosensitivity, we immunostained cells from three maxillary carcinoma cell
      lines with an anti-EGFR antibody. The intensity of staining reactivity,
      determined by means of an image analysis system, was expressed as grey value (0
      black to 255-white). The mean grey values for cell lines IMC-2, IMC-3, and IMC-4
      were 181, 210, and 222, respectively, and differed significantly (p < 0.001).
      This indicates that IMC-2 had the highest number of EGFR, followed by IMC-3 and
      IMC-4. The cells were then irradiated at 1, 2, 4, or 6 Gy, and cell survival was
      assessed by means of a standard colony-forming assay. IMC-2 had the highest
      survival rates at 1, 2 and 4 Gy, followed by IMC-3 and IMC-4. Therefore, the
      survival rates for IMC-2, IMC-3, and IMC-4 after irradiation increased in
      proportion to the amount of EGFR in each cell line. These results support the
      findings of previous clinical studies which showed that increased expression of
      EGFR was associated with higher recurrence rates of glottic and maxillary sinus
      carcinoma in patients treated with radiation therapy. The amount of EGFR in cells
      may therefore be associated with their radiosensitivity.

PMID- 9655223
TI  - Clinical role of p53 and p21WAF1/CIP1 in squamous cell carcinoma of the pyriform
      sinus.
AB  - To investigate the clinical significance of p53 and p21WAF1/CIP1 in the advanced
      squamous cell carcinoma (SCC) of the pyriform sinus, we performed
      immunohistochemical staining of p53 and p21WAF1/CIP1 on the biopsy specimens from
      patients with stage III or stage IV SCC of the pyriform sinus. The results were
      compared with clinico-pathological features, including age, histological grade,
      TNM classification, number of neck lymph node metastases on histopathological
      examination (pLN) and prognosis. Specific staining for p53 and p21WAF1/CIP1 was
      detected in 36% and 32% of the specimens, respectively. Positive staining of
      p21WAF1/CIP1 was observed not only in the p53-negative specimens but also in the
      p53-positive specimens. Age (p < 0.05) and pLN (p < 0.001) were regarded as the
      significant prognostic factors. The 5-year survival rate of the p53-positive
      patients (55%) was significantly higher than that of the p53-negative patients
      (26.5%: p < 0.03). However, there is no significant difference between the p53
      groups after controlling pLN. Although it was not statistically significant, the
      5-year survival rate of the p21WAF1/CIP1-positive patients (58.8%) was higher
      than that of the p21WAF1/CIP1-negative patients (26.9%). These results suggest
      that expressions of p53 and p21WAF1/CIP1 are independent genetic alterations that
      may play different roles in the SCC of the pyriform sinus. Expression of p53
      could not be regarded as an independent prognostic factor at this point. Further
      studies including the molecular biological analysis should be performed in order
      to determine the clinical role of p21WAF1/CIP1.

PMID- 9655224
TI  - Different KGF expression in squamous cell carcinomas of the head and neck and in
      normal mucosa.
AB  - Fibroblast growth factors (FGFs) are major factors mediating epithelial
      mesenchymal interactions in the epidermis and mucosa. In this study the
      expression of the FGFs keratinocyte growth factor (KGF), acidic FGF (aFGF) and
      basic FGF (bFGF) was examined in tumour tissue specimens from 14 patients with
      advanced-stage squamous cell carcinoma of the head and neck (SCCHN) and 3 SCC
      cell lines by reverse-transcribed polymerase chain reaction (RT-PCR) and
      immunohistochemistry. None of the SCC cell lines was positive for KGF mRNA,
      whereas all cell lines were highly positive for aFGF and bFGF. In SCCHN tissue
      samples the level of KGF mRNA expression was significantly lower than in normal
      mucosa. Tumour stroma and the submucosal areas of normal mucosa stained intensely
      with anti-KGF antibody in immunohistochemical slides, whereas tumour cell nests
      were negative. Exposure of SCC cells to KGF thus differs from normal mucosa both
      quantitatively and regarding spatial distribution. This fact and the
      overexpression of aFGF and bFGF by tumour cells potentially promote tumour
      growth, invasion and metastasis. Since these growth factors and their receptors
      are well characterized, these observations could lead to new therapeutic
      strategies in SCCHN, for instance by blocking their receptors or antisense
      targeting.

PMID- 9655225
TI  - Microbiology of cervical lymphadenitis in adults.
AB  - The microbiology of needle aspirates from 40 inflamed cervical lymph glands was
      studied for aerobic and anaerobic bacteria, fungi and mycobacteria. Forty-two
      bacterial, 11 mycobacterial and six fungal isolates were isolated. Aerobic
      bacteria only were recovered in 11 (27.5%), anaerobes alone in five (12.5%) and
      mixed aerobic and anaerobic bacteria in seven (17.5%). Mycobacterium sp. were
      recovered in 11 (27.5%) and fungi in six (15%). The recovery of anaerobes was
      associated with dental infection. Eighteen aerobic bacteria were isolated and the
      predominant ones were Staphylococcus aureus (eight isolates) and group A
      streptococci (four). Twenty-four anaerobic bacteria were recovered and the
      predominant ones were: Prevotella sp. (six), Peptostreptococcus sp. (five),
      Propionibacterium acnes (four) and Fusobacterium sp. (three). These findings
      demonstrate the role of anaerobic organisms in cervical lymphadenitis and the
      need to culture aspirated material from the glands for both aerobic and anaerobic
      microorganisms.

PMID- 9655226
TI  - Effects of pre-cues on voluntary and reflexive saccade generation. I. Anti-cues
      for pro-saccades.
AB  - Experiments on visual attention have employed both physical cues and verbal
      instructions to enable subjects to allocate attention at a location that becomes
      relevant within a perceptual or motor task some time later (cue lead time, CLT).
      In this study we have used valid visual peripheral cues (CLT between 100 and 700
      ms) to indicate the direction and location of the next saccade. A cue is
      considered valid or invalid if its meaning with respect to the next saccade is
      correct or incorrect. A cue is called an anti- or pro-cue if the side of its
      presentation is opposite to or the same as the direction of the saccade required
      on a given trial. Correspondingly, a saccade is called an anti- or pro-saccade if
      it is directed to the side opposite to or the same as the stimulus presentation.
      A condition in which the cue and the stimulus are presented on opposite sides
      provides a simple way of dissociating voluntary attention allocation from
      automatic orienting. This paper considers the anti-cue pro-saccade task: the
      subjects were instructed to use the cue to direct attention to the opposite side,
      i.e. the location, where on valid trials the saccade target would occur. In the
      companion paper we have used the same physical condition, but we have reversed
      the instructions as to saccade direction and we have reversed the meaning of the
      cue, i.e. we designed a pro-cue anti-saccade task. In this first paper, the
      saccadic reaction times (SRTs) of pro-saccades of five adult subjects were
      measured in the gap paradigm (fixation point offset precedes target onset by 200
      ms). With a CLT of 100 ms, valid anti-cues reduced the number of express saccades
      (i.e. saccades with SRTs in the range 80-120 ms) significantly compared with the
      control values (no cues). Valid anti-cues with increasingly long CLTs (100-700
      ms) resulted in an increasing incidence of anticipatory saccades and saccades
      with longer SRTs (more than 120 ms), while the frequency of express saccades
      remained below the control value. When cue and saccade target were dissociated in
      location or in both location and direction, the effects of the cueing revealed a
      much lower spatial selectivity as compared to the effects that have been
      described for voluntary attention allocation by means of central cues. The
      results suggest that voluntary allocation of attention and cue-induced automatic
      orienting not only have different time courses but also have opposite effects on
      the generation of express saccades, and different spatial selectivities. A
      possible neuronal basis of these results is discussed considering related
      findings from electrophysiological studies in monkeys.

PMID- 9655227
TI  - Effects of pre-cues on voluntary and reflexive saccade generation. II. Pro-cues
      for anti-saccades.
AB  - The reaction times of saccades (SRT) to a suddenly presented visual stimulus (pro
      saccade) can be decreased and a separate mode of express saccades can occur when
      a gap paradigm is used (i.e. fixation-point offset precedes target onset by 200
      ms). A valid peripheral cue, presented briefly (100 ms) before target onset, has
      been found to facilitate the generation of saccades to the target, thereby
      increasing the frequency of express saccades and decreasing the mean latency.
      This facilitation occurs only for cues that correctly indicate the direction of
      the subsequent target presentation (valid cues). The present study investigates
      the effects of valid cues on SRTs and error rate in the anti-saccade task
      (saccades in the direction opposite to the stimulus) by systematically varying
      the cue lead time (CLT) and using the gap and overlap conditions, i.e. fixation
      point remains on throughout the trial. For a CLT of 100 ms, both reaction times
      and error rates were significantly increased. With increasing CLT (200-500 ms),
      both the reaction times of the anti-saccades and the error rates returned to
      approximately control level, with CLT more than 200 ms in both the gap and the
      overlap condition. Additional experiments using non-informative cues in the
      overlap task showed that the reaction times of correct anti-saccades and the
      error rate were decreased when cue and stimulus appeared at the same side.
      Analysis of the erratic pro-saccades revealed that almost all of them were
      corrected, i.e. they were followed by a second saccade towards the required
      location. It is found that the correction times were usually very short, with
      intersaccadic intervals between 0 and 150 ms. We suggest that the orienting
      mechanism, elicited by a transient peripheral cue, relates to the command and the
      decision to make a pro- rather than an anti-saccade. The cue elicits pro
      orienting towards its position when a pro-saccade is required, and anti-orienting
      when an anti-saccade is required. The orienting effect is transient and decays
      with CLTs of more than 200 ms; this result holds for both anti-saccades and pro
      saccades. Since subjects reported that they could not prevent the erratic pro
      saccades or were often not aware of them, we conclude that this orienting
      mechanism occurs automatically, beyond voluntary control.

PMID- 9655228
TI  - Comparison of sympathetic sprouting in sensory ganglia in three animal models of
      neuropathic pain.
AB  - Sympathetic postganglionic fibers sprout in the dorsal root ganglion (DRG) after
      peripheral nerve injury. Therefore, one possible contributing factor of
      sympathetic dependency of neuropathic pain is the extent of sympathetic sprouting
      in the DRG after peripheral nerve injury. The present study compared the extent
      of sympathetic sprouting in the DRG as well as in the injured peripheral nerve in
      three rat neuropathic pain models: (1) the chronic constriction injury model
      (CCI); (2) the partial sciatic nerve ligation injury model (PSI); and (3) the
      segmental spinal nerve ligation injury model (SSI). All three methods of
      peripheral nerve injury produced behavioral signs of ongoing and evoked pain with
      some differences in the magnitude of each pain component. The density of
      sympathetic fibers in the DRG was significantly higher at all examined
      postoperative times than controls in the SSI model, while it was somewhat higher
      than controls only at the last examined postoperative time (20 weeks) in the CCI
      and PSI models. Therefore, data suggest that, although sympathetic changes in the
      DRG may contribute to neuropathic pain syndromes in the SSI model, other
      mechanisms seem to be more important in the CCI and PSI models at early times
      following peripheral nerve injury.

PMID- 9655229
TI  - Short-term changes in neck muscle and eye movement responses following unilateral
      vestibular neurectomy in the cat.
AB  - The purpose of this study was to investigate changes in neck muscle and eye
      movement responses during the early stages of vestibular compensation (first 3
      weeks after unilateral vestibular neurectomy, UVN). Electromyographic (EMG)
      activity from antagonist neck extensor (splenius capitis) and flexor (longus
      capitis) muscles and eye movements were recorded during sinusoidal visual and/or
      otolith vertical linear stimulations in the 0.05-1 Hz frequency range
      (corresponding acceleration range 0.003-1.16 g) in the head-fixed alert cat.
      Preoperative EMG activity from the splenius and longus capitis muscles showed a
      pattern of alternate activation of the antagonist neck muscles in all the cats.
      After UVN, two motor strategies were observed. For three of the seven cats, the
      temporal activation of the individual neck muscles was the same as that recorded
      before UVN. For the other four cats, UVN resulted in a pattern of coactivation of
      the flexor and extensor neck muscles because of a phase change of the splenius
      capitis. In both subgroups, the response patterns of the antagonist neck muscles
      were consistent for each cat independently of the experimental conditions,
      throughout the 3 weeks of testing. Cats displaying alternate activation of
      antagonist neck muscles showed an enhanced gain of the visually induced neck
      responses, particularly in the high range of stimulus frequency, and a gain
      decrease in the otolith-induced neck responses at the lowest frequency (0.25 Hz)
      only. By contrast, for cats with neck muscle coactivation, the gain of the
      visually induced neck responses was basically unaffected relative to preoperative
      values, whereas otolith-induced neck responses were considerably decreased in the
      whole range of stimulation. As concerns oculomotor responses, results in the two
      subgroups of cats were similar. The optokinetic responses were not affected by
      the vestibular lesion. On the contrary, otolith-induced eye responses showed a
      gain reduction and a phase lead. Deficits and short-term changes after UVN of
      otolith- and semicircular canal-evoked collic and ocular responses are compared.

PMID- 9655230
TI  - Eye movements evoked by proprioceptive stimulation along the body axis in humans.
AB  - Proprioceptive input arising from torsional body movements elicits small
      reflexive eye movements. The functional relevance of these eye movements is still
      unknown so far. We evaluated their slow components as a function of stimulus
      frequency and velocity. The horizontal eye movements of seven adult subjects were
      recorded using an infrared device, while horizontal rotations were applied at
      three segmental levels of the body [i.e., between head and shoulders (neck
      stimulus), shoulders and pelvis (trunk stimulus), and pelvis and feet (leg
      stimulus)]. The following results were obtained: (1) Sinusoidal leg stimulation
      evoked an eye response with the slow component in the direction of the movement
      of the feet, while the response to trunk and neck stimulation was oriented in the
      opposite direction (i.e., in that of the head). (2) In contrast, the gain
      behavior of all three responses was similar, with very low gain at mid- to high
      frequencies (tested up to 0.4 Hz) but increasing gain at low frequencies (down to
      0.0125 Hz). We show that this gain behavior is mainly due to a gain nonlinearity
      for low angular velocities. (3) The responses were compatible with linear
      summation when an interaction series was tested in which the leg stimulus was
      combined with a vestibular stimulus. (4) There was good correspondence of the
      median gain curves when eye responses were compared with psychophysical responses
      (perceived body rotation in space; additionally recorded in the interaction
      series). However, correlation of gain values on a single-trial basis was poor.
      (5) During transient neck stimulation (smoothed position ramp), the neck response
      noticeably consisted of two components -- an initial head-directed eye shift
      (phasic component) followed by a shift in the opposite direction (compensatory
      tonic component). Both leg and neck responses can be described by one simple,
      dynamic model. In the model the proprioceptive input is fed into the gaze network
      via two pathways which differ in their dynamics and directional sign. The model
      simulates either leg or neck responses by selecting an appropriate weight for the
      gain of one of the pathways (phasic component). The interaction results can also
      be simulated when a vestibular path is added. This model has similarities to one
      we recently proposed for human self-motion perception and postural control. A
      major difference, though, is that the proprioceptive input to the gaze
      stabilizing network is weak (restricted to low velocities), unlike that used for
      perception and postural control. We hold that the former undergoes involution
      during ontogenesis, as subjects depend on the functionally more appropriate
      vestibulo-ocular reflex. Yet, the weak proprioceptive eye responses that remain
      may have some functional relevance. Their tonic component tends to stabilize the
      eyes by slowly shifting them toward the primary head position relative to the
      body support. This applies solely to the earth-horizontal plane in which the
      vestibular signal has no static sensitivity.

PMID- 9655231
TI  - Influence of hypoglycemic coma on brain water and osmolality.
AB  - To study the effects of pronounced hypoglycemia on brain osmolality and brain
      edema formation, fasted rats were rendered hypoglycemic by injection of insulin,
      and subjected to 30 min of hypoglycemic coma. Recovery was accomplished by
      glucose administration. The change in water content in different brain regions
      was measured as a change in specific gravity after 30 min of hypoglycemic coma,
      or 30, 60, and 180 min after glucose administration. Plasma and brain tissue
      osmolality were measured in separate animals. The results show a significant
      decrease in specific gravity (increase in water content) in all structures
      measured (caudoputamen, neocortex, hippocampus, and cerebellum) at the end of the
      period of coma, as well as after 30 min and 60 min of recovery. At 180 min of
      recovery, brain water was normalized. The edema affected all structures to the
      same degree regardless of their vulnerability to hypoglycemic damage. Brain
      tissue osmolality showed a tendency to decrease with decreasing tissue glucose
      content. The decrease was significant (P<0.01) at 30 min of isoelectric coma. In
      the recovery phase, normal brain osmolality was restored within 30 min.
      Measurements of blood-brain barrier (BBB) permeability after 30 min of
      hypoglycemic coma showed no extravasation of Evan's blue, though a small but
      significant increase in the permeability for aminoisobutyric acid (AIB) in
      caudoputamen and in cerebellum was found. To analyze the importance of tissue
      acidosis for formation of edema, hypoglycemic animals were made acidotic by
      increasing the CO2 concentration in inspired air to produce an arterial plasma pH
      of 6.8-6.9. In these animals the edema was of a similar degree to the normocapnic
      animals, and the permeability for AIB was normal. We conclude that osmolytic
      mechanisms are not the primary cause of the selective neuronal vulnerability in
      hypoglycemic coma. Furthermore, the BBB is largely intact during a hypoglycemic
      insult.

PMID- 9655232
TI  - Consistency of unitary shapes in dual lead recordings from myelinated fibres in
      human peripheral nerves: evidence for extracellular single-unit recordings in
      microneurography.
AB  - Percutaneous microneurography is a powerful technique allowing studies of
      activity in single nerve fibres of conscious humans. However, the mechanisms by
      which single-unit recordings are achieved with this technique are not fully
      understood. To further elucidate these mechanisms, dual-lead recordings, using a
      modified concentric needle electrode with two separate recording surfaces at the
      tip, were performed in normal subjects. Sixty-two single units supplied by large
      myelinated afferents were studied. The majority (90%) of the units were recorded
      simultaneously on both surfaces but with different action potential amplitudes.
      Four types of unitary waveforms were encountered. The potentials recorded on the
      two channels were of the same type, although occasionally some details differed.
      Parallel waveform changes of the same units occurred simultaneously on the two
      surfaces. A displacement of a single fibre from one recording surface to the
      other with or without concomitant waveform-type transitions was observed when the
      electrode was slightly repositioned intraneurally. The results provided direct
      evidence to confirm that concentric needle electrodes record single-unit activity
      extracellularly from myelinated nerve fibres, probably at or close to a node of
      Ranvier. All the types of action potentials encountered with conventional
      tungsten electrodes were also identified in dual-channel recordings with
      concentric electrodes, which casts doubt on the previous explanation that single
      unit activity recorded with tungsten electrodes is derived from intracellular
      sources. Some biological and technical aspects of the findings are discussed,
      especially concerning the applicability of in vivo measurements of the time
      course of the action potentials in humans and ways to improve microneurography
      towards multichannel recordings.

PMID- 9655233
TI  - Coordination of two-joint rectus femoris and hamstrings during the swing phase of
      human walking and running.
AB  - It has been hypothesized previously that because a strong correlation was found
      between the difference in electromyographic activity (EMG) of rectus femoris (RF)
      and hamstrings (HA; EMG(RF)-EMG(HA)) and the difference in the resultant moments
      at the knee and hip (Mk-Mh) during exertion of external forces on the ground by
      the leg, input from skin receptors of the foot may play an important role in the
      control of the distribution of the resultant moments between the knee and hip by
      modulating activation of the two-joint RF and HA. In the present study, we
      examined the coordination of RF and HA during the swing phase of walking and
      running at different speeds, where activity of foot mechanoreceptors is not
      modulated by an external force. Four subjects walked at speeds of 1.8 m/s and 2.7
      m/s and ran at speeds of 2.7 m/s and 3.6 m/s on a motor-driven treadmill. Surface
      EMG of RF, semimembranosus (SM), and long head of biceps femoris (BF) and
      coordinates of the four leg joints were recorded. An inverse dynamics analysis
      was used to calculate the resultant moments at the ankle, knee, and hip during
      the swing phase. EMG signals were rectified and low-pass filtered to obtain
      linear envelopes and then shifted in time to account for electromechanical delay
      between EMG and joint moments. During walking and running at all studied speeds,
      mean EMG envelope values of RF were statistically (P<0.05) higher in the first
      half of the swing (or at hip flexion/knee extension combinations of joint
      moments) than in the second half (or at hip extension/knee flexion combinations
      of joint moments). Mean EMG values of BF and SM were higher (P<0.05) in the
      second half of the swing than in the first half. EMG and joint moment peaks were
      substantially higher (P<0.05) in the swing phase of walking at 2.7 m/s than
      during the swing phase of running at the same speed. Correlation coefficients
      calculated between the differences (EMG(RF)-EMG(HA)) and (Mk-Mh), taken every 1%
      of the swing phase, were higher than 0.90 for all speeds of walking and running.
      Since the close relationship between EMG and joint moments was obtained in the
      absence of an external force applied to the foot, it was suggested that the
      observed coordination of RF and HA can be regulated without a stance-specific
      modulation of cutaneous afferent input from the foot. The functional role of the
      observed coordination of RF and HA was suggested to reduce muscle fatigue.

PMID- 9655234
TI  - Differential effects of load stiffness on matching pinch force, finger span, and
      effort.
AB  - Disparities in load stiffness were used to differentiate and characterize pinch
      force, finger-span, and pinch-effort matching in two experiments. All subjects
      squeezed a spring-loaded manipulandum in each hand using three-finger pinch.
      Subjects in the first experiment were instructed explicitly to match one of the
      three continua. Subjects matching force or span were told to attend carefully to
      sensations from the hand or arm and to ignore differences in the effort required
      to make the sensations equal. They had to achieve and hold a particular target
      force with the reference hand and then match force or span with the opposite
      hand, usually against a spring with a different stiffness. These subjects were
      given as much time as necessary to make their matches and were told which hand
      was serving as the reference in each trial. Effort-matching subjects were told to
      ignore peripheral sensations and to match effort or motor commands. These
      subjects were not told which hand was the reference and were given only 1 s to
      make a match, so they made matches by rapidly squeezing both manipulanda
      simultaneously and, presumably, with the same voluntary motor command. The
      matching behaviors of the three groups were clearly distinguishable and were
      consistent with instructions. Results were similar whether different subjects
      were assigned different instructions or the same subjects performed all three
      match types. In a second experiment, naive subjects were given purposely
      ambiguous instructions without reference to a specific continuum and had no time
      or accuracy constraints. Subjects produced the same three sensorimotor behaviors
      obtained with explicit instructions, showing that the different behaviors were
      not artifacts of strict protocols. Taken together, the results show that force,
      span, and effort are distinct sensorimotor continua that can be judged reliably.

PMID- 9655235
TI  - Hand trajectories of vertical arm movements in one-G and zero-G environments.
      Evidence for a central representation of gravitational force.
AB  - The purpose of the present experiment was to study the way in which the central
      nervous system (CNS), represents gravitational force during vertical arm pointing
      movements. Movements in upward (against gravity) and downward (with gravity)
      directions, with two different mass loads (hand empty and with a hand-held 0.5-kg
      weight) were executed by eight subjects in a normal gravitational environment.
      Movements by two cosmonauts, in the two directions, were also tested in a state
      of weightlessness. Analyses focused upon finger trajectories in the sagittal
      plane. Subjects in a normal gravitational environment showed curved paths for
      both directions and weight conditions. In addition, downward movements showed
      significantly smaller curvatures than upward movements. Movement times were
      approximately the same for all the experimental conditions. Curvature differences
      between upward and downward movements persisted during space flight and
      immediately postflight. Movement times from both cosmonauts increased slightly
      during flight, but returned to normal immediately on reentry in a one-G
      environment. Results from the present study provide evidence that gravity is
      centrally represented in an anticipatory fashion as a driving force during
      vertical arm movement planning.

PMID- 9655236
TI  - Calcium metabolism of focal and penumbral tissues in rats subjected to transient
      middle cerebral artery occlusion.
AB  - The present experiments were undertaken to define changes in tissue calcium
      metabolism in focal and perifocal ("penumbral") tissues following 2 h of
      transient middle cerebral artery occlusion (MCAO) in rats, induced with an
      intraluminal filament occlusion technique. The extracellular calcium
      concentration ([Ca2+]e) was measured with ion-selective microelectrodes in
      neocortical focus and penumbra. For measurement of total tissue calcium content,
      tissue samples from these areas were collected and analyzed with atomic
      absorption spectrometry. During MCAO, [Ca2+]e in a neocortical focal area fell
      from a normal value of about 1.2 mM to values around 0.1 mM, suggesting
      translocation of virtually all extracellular calcium to intracellular fluids.
      Recirculation was accompanied by re-extrusion of calcium within 5-7 min; however,
      [Ca2+]e never returned to normal but stabilized at about 50% of the control value
      for the first 6 h, and decreased further after 24 h. In penumbral areas, [Ca2+]e
      showed the expected transient decreases associated with spreading depression-like
      (or ischemic) depolarization waves. Recirculation was followed by return of
      [Ca2+]e towards normal values. In the focus, water content increased from about
      79% to about 80.4% at the end of the 2-h period of ischemia. After 2 h and 4 h of
      recirculation, the edema was aggravated (mean values 81.9% and 81.2%,
      respectively). After 6 h and 24 h, the edema was more pronounced (83.6% and
      83.8%, respectively). In the penumbra, no significant edema was observed until 6
      h and 24 h of recirculation. The total tissue calcium content in the focus
      (expressed by unit dry weight) increased at the end of the ischemia period
      demonstrating calcium translocation from blood to tissue. After 6 h and 24 h, the
      content increased two- to threefold, compared with control. Changes in the
      penumbra were qualitatively similar but less pronounced, and a significant
      increase was not observed until after 6 h of recirculation. The results suggest
      that 2 h of MCAO leads to a profound perturbation of cell calcium metabolism. In
      focal areas, cells fail to extrude the calcium that is gradually accumulated
      during reperfusion and show massive calcium overload after the first 4-6 h of
      recirculation. Penumbral tissues show a similar increase in calcium concentration
      after 6 h of recirculation.

PMID- 9655237
TI  - Characteristics of target-reaching in cats. III. Lifting and protraction with an
      obstacle in the movement path and after its removal.
AB  - Three cats were trained to perform target-reaching to a horizontal tube with food
      placed at shoulder level, and the kinematic characteristics of the movements were
      investigated by recording the trajectory of the wrist. From the very onset of
      training, a vertical obstacle was placed in front of the cats. The obstacle
      forced the animals to perform movements with an initial phase dominated by limb
      lifting to position the wrist above the obstacle, followed by a second phase of
      protraction towards the tube; in the sagittal plane, the movement paths were
      segmented with an upwards convexity. After a training period of 1 year (about
      7000 movements), the obstacle was removed. All cats then quickly (within a few
      trials) changed the trajectory so that the main part of protraction now occurred
      in parallel with limb-lifting during the first half of the movement. The initial
      slope of the sagittal movement path became less steep and the upwards convexity
      less pronounced. Such trajectories, which predominated for several experiments
      after removal of the obstacle, were only slightly different from those observed
      in control cats not trained with an obstacle. The results are discussed in
      relation to a previously proposed hypothesis of motor "imprinting" during
      extensive training in a particular experimental paradigm.

PMID- 9655238
TI  - Activation of the ornithine decarboxylase-polyamine system and induction of c-fos
      and p53 expression in relation to excitotoxic neuronal apoptosis in normal and
      microencephalic rats.
AB  - Microencephalic rats obtained by gestational treatment with the DNA alkylating
      agent methylazoxymethanol, show a remarkable lack of sensitivity to excitotoxic
      neuropathology caused by systemic injections of the convulsant neurotoxin kainic
      acid. Taking advantage of this, we have studied in these rats, as well as in
      normal rats, the relationship between the induction of cellular signals
      supposedly related to cell death and the neuronal apoptosis consequent to kainic
      acid administration. While normal rats responded to the excitatory insult with a
      large and relatively long lasting increase of the activity of the enzyme
      ornithine decarboxylase and of the concentration of putrescine in some brain
      regions, these alterations were much smaller in microencephalic rats. Expression
      of c-fos in brain regions sensitive to kainic acid was quicker but lasted a
      noticeably shorter time in microencephalic rats as compared to normal animals. A
      profusion of apoptotic neurons, labeled by an in situ technique, were observed in
      the olfactory cortex, amygdala and hippocampus of normal rats injected with
      kainic acid, in particular 48 h and 72 h after drug administration. At
      corresponding time intervals and with similar topographic localization, neurons
      expressing p53 protein were observed. By contrast, microencephalic rats displayed
      only in a few cases and in a small number apoptotic neurons in restricted areas
      of the ventral hippocampus and entorhinal cortex. Noticeably, in these cases
      small populations of p53-expressing neurons were also present in the same areas.
      The present observations clearly show that oncogenes such as c-fos and p53, as
      well as ornithine decarboxylase which behaves as an immediate-early gene in the
      brain under certain circumstances, undergo noticeably lower and/or shorter
      induction in microencephalic rats exposed to excitotoxic stimuli. In these rats,
      therefore, the cellular signalling pathways studied here and related to
      excitotoxic sensitivity and commitment to cell death are downregulated as a
      probable consequence of altered brain wiring.

PMID- 9655239
TI  - Sensitivity and density of glutamate receptor subtypes in the hippocampal
      formation are altered in pentylenetetrazole-kindled rats.
AB  - Kindling induced by 13 intraperitoneal injections of 40 mg/kg pentylenetetrazole
      (PTZ) over a period of 4 weeks resulted in a significant long-lasting increase in
      both the convulsive susceptibility of animals to the convulsant and the density
      of the specific [3H]-L-glutamate binding sites in the hippocampus. The
      quisqualate- and kainate-sensitive [3H]-L-glutamate binding sites were increased
      24 h after the final PTZ injection, whereas the N-methyl-D-aspartate (NMDA)
      sensitive sites had only a tendency to be enhanced. Furthermore, we investigated
      [3H]-L-glutamate binding on metabotropic receptors and found a significant
      increase in the hippocampus following PTZ kindling. In addition, in hippocampal
      tissue of kindled rats (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid
      (trans-ACPD)-stimulated inositol phosphate formation is increased. It can be
      concluded that the increase in metabotropic glutamate receptor (mGluR) density
      may be the expression of a specific enhancement in susceptibility of the
      glutamatergic systems to this excitatory amino acid developing in the course of
      PTZ-induced kindling.

PMID- 9655240
TI  - Hemispheric asymmetries and bimanual asynchrony in left- and right-handers.
AB  - It is known that, when both forearms are rotated rhythmically and symmetrically,
      the dominant hand leads in time by about 25 ms, irrespective of movement speed.
      Positron emission tomography was used to test the hypothesis that the asynchrony
      results from a functional hemispheric asymmetry. We found that in normal, adult
      right-handers portions of the motor and premotor motor areas are more active in
      the left than in the right hemisphere. The converse pattern was observed in left
      handers. The results suggest that at least some components of the neural
      processing involved in bimanual coordination are carried out only in the
      hemisphere contralateral to the dominant hand. In particular, between-hands
      asynchrony may reflect the time for dispatching pace-setting commands to the
      contralateral hemisphere.

PMID- 9655241
TI  - The influence of vision on the automatic postural muscle responses of newly
      standing and newly walking infants.
AB  - In adults, visual inputs do not appear to contribute significantly to automatic
      postural muscle responses (90-100 ms latency) activated by transient support
      surface displacements causing threats to standing balance, but are activated
      through slow pathways with latencies of more than 200 ms. However, it has been
      shown that the postural sway behavior of early walking infants is strongly
      influenced by visual flow cues that falsely signal self-movement. To determine
      whether there also are significant contributions of vision to automatic postural
      muscle responses in this age group, two groups of infants were tested on a
      moveable platform; pre-walkers (n=6) and early walkers (n=6). Pre-walkers did not
      show any measurable effect of visual condition (vision vs no vision) on muscle
      response characteristics. However, the integrated gastrocnemius activity of early
      walkers increased significantly in vision versus no vision conditions (P<0.05).
      These results show that visual cues contribute to, or modulate, the automatic
      postural responses in children who are in the developmental transition to
      independent walking.

PMID- 9655242
TI  - Cloning, characterization, and mapping of human homolog of mouse T-cell death
      associated gene.
AB  - To establish immunologic autotolerance, self-reactive immature thymocytes are
      eliminated by negative selection during T-cell development in the thymus. Self
      reactive clones undergo apoptosis after stimulation via the T-cell receptor
      (TCR). The process of cell selection is determined by the dedication of the TCR
      for tolerogenic antigen/major histocompatibility complex. We have cloned a novel
      human gene that is highly homologous in the transmembrane and G protein-coupling
      domains to mouse T-cell death-associated gene 8 (TDAG8). The gene, human TDAG8
      (hTDAG8), which belongs to the G protein-couple receptor superfamily, encodes a
      protein of 337 amino acids. An expressed sequence tag (EST) corresponding to
      hTDAG8 was identified from a human thyroid cDNA library and subsequently used to
      isolate a full-length genomic clone. Northern blot analysis revealed that the
      hTDAG8 gene is expressed predominantly in lymphoid tissues, including peripheral
      blood leukocytes, spleen, lymph nodes, and thymus. Stably transfected mammalian
      CHO cells were generated, and heterologous expression of hTDAG8 was confirmed by
      Northern blot analysis. Fluorescent in situ hybridization (FISH) revealed that
      hTDAG8 maps to human chromosome 14q31-32.1, a region in which abnormalities
      associated with human T-cell lymphoma or leukemia are found. Taken together,
      these data implicate the hTDAG8 gene in T-cell-associated diseases in humans, but
      its actual physiological and pathological role in the human immune system needs
      further investigation.

PMID- 9655243
TI  - Expression of the gene encoding metallothionein-3 in organs of the reproductive
      system.
AB  - Metallothionein-3 (MT-3) is a new MT gene-family member that inhibits survival of
      rat neurons cultured in presence of brain extracts. Contrary to other MT genes,
      which are expressed in most tissues and which are highly inducible by metals, MT
      3 expression was reported to be mainly in the brain, and it failed to respond to
      metals in vivo. We show here that MT-3 mRNA is present in several organs other
      than the brain, as assayed by Northern analyses. In the rat, MT-3 mRNA was
      detected in the testis, prostate, epididymis, tongue, ovary, uterus, stomach,
      heart, and seminal vesicles. The MT-3 mRNA levels in the testis, epididymis,
      prostate, and tongue were 22% of those in brain, while in ovary, uterus, and
      stomach, they were 4% of the brain level, and they were lower still in the other
      organs. The MT-3 gene was not inducible by CdCl2 or lipopolysaccharide in rat
      testis and prostate. In the mouse and the human, relative MT-3 mRNA levels were
      lower than those found in the rat when compared with those present in brain.
      Testicular MT-3 transcript levels remained quite constant during rat postnatal
      development in animals aged from 6 to 43 days. In situ hybridization analyses on
      human testis sections showed that MT-3 mRNA was present at different levels in
      both the Leydig cells and the seminiferous tubules. In orchiectomized rats,
      prostatic MT-3 mRNA was decreased by 75%, and injections of dihydrotestosterone
      restored MT-3 mRNA levels to control values. Overall, these results show that MT
      3 tissue-specific gene expression is broader than previously reported and provide
      new experimental systems to study the function and mechanism of action of the MT
      3 protein.

PMID- 9655244
TI  - Production of recombinant hydroxylated human type III collagen fragment in
      Saccharomyces cerevisiae.
AB  - A recombinant hydroxylated fragment of human type III collagen has been produced
      in Saccharomyces cerevisiae by coordinated coexpression of a collagen gene
      fragment together with both the alpha- and beta-subunit genes for prolyl-4
      hydroxylase (EC 1.14.11.2). The collagen fragment consisted of 255 residues of
      the helical domain and the complete C-telopeptide and C-propeptide domains. It
      was inserted under the control of the ethanol-inducible ADH2 promoter in a
      multicopy, TRP1-selectable, yeast expression vector, YEpFlag1. The
      prolyihydroxylase subunit genes were cloned on either side of a bidirectional
      galactose-inducible promoter in a low-copy minichromosome yeast expression
      vector, pYEUra3, which is URA3 selectable. Coordinated expression of the three
      different gene products after cotransformation into S. cerevisiae was detected by
      immunoblotting. Amino acid analysis of an immunoreactive collagen fraction
      demonstrated the presence of hydroxyproline, while the presence of a triple
      helical domain in the collagen fragment was demonstrated by its resistance to
      pepsin proteolysis.

PMID- 9655245
TI  - Identification of scaffold/matrix attachment region in recurrent site of
      woodchuck hepatitis virus integration.
AB  - Scaffold or matrix attachment regions (S/MARs) are noncoding genomic DNA
      sequences displaying in vitro selective binding affinity for nuclear scaffold.
      They have been reported to be involved in the physical attachment of genomic DNA
      to the nuclear scaffold, and thus in the organization of the chromatin in
      functional loops or domains, and in the regulation of gene expression. In this
      work, we report the identification of an S/MAR in a woodchuck chromosomal locus,
      named b3n, previously described as a recurrent site of woodchuck hepatitis virus
      (WHV) DNA integration in woodchuck hepatocellular carcinoma (HCC). The 4.3-kb
      sequence of this locus contains several Alu-like repeats and a gag-like coding
      region with frameshift mutations. Computer analysis revealed the presence of a
      region with unusually high AT content, typical of most S/MARs, and of specific
      motifs (A boxes, T boxes, topoisomerase II sites, and unwinding elements)
      overlapping or in proximity to the region with high AT content, predicting that
      b3n might contain an S/MAR. Fragments of the b3n locus were isolated by
      conventional and inverse PCR techniques. In in vitro binding experiments with
      both heterologous and autologous scaffold preparations, a 592-bp fragment
      spanning the region rich in S/MAR features showed marked scaffold affinity, which
      was specific when autologous scaffolds were used. The presence of an S/MAR at the
      b3n locus and its nature as a recurrent WHV integration site in HCC suggest the
      involvement of S/MAR elements in some of the mechanisms leading to liver
      oncogenesis.

PMID- 9655246
TI  - Linear amplification mapping of polycyclic aromatic hydrocarbon-reactive
      sequences in H-ras gene.
AB  - Linear amplification, or primer directed single-strand DNA synthesis, is commonly
      used in applications such as cycle sequencing and mapping replication block sites
      in DNA. Although linear amplification reactions would be expected to synthesize
      full-length single-stranded DNA, the synthesis is often prematurely terminated.
      We describe the optimization of a linear amplification protocol for synthesizing
      a full-length (985-nt) single-stranded pBR322 segment. The enzyme activities of
      five DNA polymerases commonly used in PCR amplification, namely, AmpliTaq,
      Stoffel fragment, Tth, Pfu, and Vent, were tested either singly or in
      combination. The results indicate that the additive action of small amounts of
      proofreading DNA polymerases to a nick-translating polymerase is optimum for
      linear amplification. From these results, a linear amplification protocol was
      developed to map DNA synthesis-blocking sites generated by the reaction of (+/-)
      anti-benzo[a]pyrene-7,8-diol-9,10-epoxide, or anti- or syn-dibenzo[a,l]pyrene
      9,10-diol-11,12-epoxide with H-ras DNA surrounding the oncogenic codon 61 region.
      The results indicate that the central A of H-ras codon 61 (CAA) reacts with these
      polycyclic aromatic hydrocarbons.

PMID- 9655247
TI  - Effects of bulky polycyclic aromatic hydrocarbon adducts on DNA replication by
      exonuclease-deficient T7 and T4 DNA polymerases.
AB  - In vitro DNA replication by exonuclease-deficient T7 DNA polymerase (Sequenase)
      and an exonuclease deficient T4 DNA polymerase was examined on a 244-nucleotide
      DNA template treated with three electrophilic polycyclic aromatic hydrocarbon
      (PAH) metabolites: racemic trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10
      tetrahydrobenzo[a]pyrene (BaPDE), trans-2,3-dihydroxy-anti-1,10b-epoxy-10b,1,2,3
      tetrahydrofluoranthene (FADE), or 3,4-epoxy-3,4-dihydrocyclopenta[cd]pyrene
      (CPPE). The DNA replication terminated opposite template guanines and, to a
      lesser extent, at template adenines, as expected, as purines were modified
      preferentially by the chemical treatments. Analysis of the products synthesized
      on the damaged templates indicated that bypass replication by Sequenase proceeded
      in three steps: (1) replication first terminated one base 3' to each adduct; (2)
      a nucleotide was then incorporated opposite the PAH-modified base; and (3)
      replication continued at some sites to give full bypass of the lesions. The rate
      of lesion bypass was affected by the type of chemical adduct, the sequence
      context of the adduct, and the concentration of deoxynucleoside triphosphates.
      Short DNA repeats appeared to facilitate translesion replication.

PMID- 9655248
TI  - Characterization of the human Megalin/LRP-2 promoter in vitro and in primary
      parathyroid cells.
AB  - The gp330/Megalin/LRP-2 protein belongs to the low-density lipoprotein receptor
      gene family and is believed to function as an endocytic receptor for the uptake
      of lipoproteins and many other ligands. Other functions of this protein may
      include a role in calcium sensing in the parathyroid glands and other tissues. In
      order to study the transcriptional regulation of the human LRP-2 gene, a clone
      containing the 5'-flanking region was isolated from a genomic DNA library, and a
      transient transfection protocol for primary bovine parathyroid cells was
      established. RNA mapping techniques located the transcriptional start site 136 bp
      upstream of the initiation codon. Transient expression in several cell types,
      including primary parathyroid cells, and in vitro transcription in HeLa cell
      nuclear extracts showed that sequences between -120 and -35 were important for
      activated transcription. This region contains consensus binding sites (GC boxes)
      for transcription factor Sp1. Mutation of the GC boxes abolished binding of Sp1
      in vitro and resulted in reduced transcription in vitro and in transfected cells.
      Furthermore, Sp1 stimulated transcription when tethered to the LRP-2 core
      promoter through a heterologous DNA-binding domain. Through site-directed
      mutagenesis, we identified a novel atypical TATA element with the sequence
      TAGAAAA. Intriguingly, this sequence motif was shown previously not to mediate
      transcription in a systematic mutational analysis of the TATA motif. Possible
      roles of this novel TATA element in the regulation of transcription initiation
      are discussed. The isolation and characterization of the LRP-2 promoter and the
      5'-flanking region and the establishment of a transient expression assay in
      primary parathyroid cells will facilitate studies on the regulatory mechanisms of
      the LRP-2 gene and of other genes expressed in the parathyroid glands.

PMID- 9655249
TI  - Structural and functional analysis of mouse Msx1 gene promoter: sequence
      conservation with human MSX1 promoter points at potential regulatory elements.
AB  - Vertebrate Msx genes are related to one of the most divergent homeobox genes of
      Drosophila, the muscle segment homeobox (msh) gene, and are expressed in a well
      defined pattern at sites of tissue interactions. This pattern of expression is
      conserved in vertebrates as diverse as quail, zebrafish, and mouse in a range of
      sites including neural crest, appendages, and craniofacial structures. In the
      present work, we performed structural and functional analyses in order to
      identify potential cis-acting elements that may be regulating Msx1 gene
      expression. To this end, a 4.9-kb segment of the 5'-flanking region was sequenced
      and analyzed for transcription-factor binding sites. Four regions showing a high
      concentration of these sites were identified. Transfection assays with fragments
      of regulatory sequences driving the expression of the bacterial lacZ reporter
      gene showed that a region of 4 kb upstream of the transcription start site
      contains positive and negative elements responsible for controlling gene
      expression. Interestingly, a fragment of 130 bp seems to contain the minimal
      elements necessary for gene expression, as its removal completely abolishes gene
      expression in cultured cells. These results are reinforced by comparison of this
      region with the human Msx1 gene promoter, which shows extensive conservation,
      including many consensus binding sites, suggesting a regulatory role for them.

PMID- 9655250
TI  - Repression of the telomerase catalytic subunit by a gene on human chromosome 3
      that induces cellular senescence.
AB  - The cellular senescence program is controlled by multiple genetic pathways, one
      of which involves the regulation of telomerase and telomere shortening. The
      introduction of a normal human chromosome 3 into the human renal cell carcinoma
      cell line RCC23 caused repression of telomerase activity, progressive shortening
      of telomeres, and restoration of the cellular senescence program. We attributed
      the repression of telomerase activity to the marked downregulation of the gene
      encoding the catalytic subunit of telomerase (hEST2/hTRT) but not another protein
      component (TP1/TLP1) or the RNA component of telomerase. These results suggest
      that a senescence-inducing gene on chromosome 3 controls hEST2/hTRT gene
      expression either directly or indirectly and support the notion that hEST2/hTRT
      is the major determinant of telomerase enzymatic activity in human cells.

PMID- 9655251
TI  - Altered expression of epidermal growth factor receptor ligands in tumor promoter
      treated mouse epidermis and in primary mouse skin tumors induced by an initiation
      promotion protocol.
AB  - Multiple epidermal growth factor receptor (EGFr) ligands have been identified,
      including transforming growth factor alpha (TGFalpha), heparin-binding epidermal
      growth factor (HB-EGF), amphiregulin (AR), and betacellulin (BTC). Previous work
      from our laboratory demonstrated that TGFalpha mRNA and protein are upregulated
      in epidermis during tumor-promoter treatment of mouse skin and in skin tumors
      produced by initiation-promotion regimens. The purpose of the study described
      here was to explore the role of other EGFr ligands in multistage skin
      carcinogenesis. A single topical treatment of either 12-O-tetradecanoylphorbol-13
      acetate (TPA) or chrysarobin or a single full-thickness wound induced the
      expression of HB-EGF and AR in mRNA samples isolated from whole mouse skin.
      However, only full-thickness wounding significantly elevated expression of the
      BTC transcript. The levels of HB-EGF and AR transcripts were significantly
      elevated in skin tumors (both papillomas and squamous cell carcinomas) induced by
      initiation-promotion protocols. BTC transcript levels were low and barely
      detectable in all skin tumors examined. The level of keratinocyte growth factor
      (KGF) mRNA was also examined as a possible mechanism for upregulation of EGFr
      ligands. Only full-thickness wounding significantly elevated KGF transcript
      levels in whole-skin RNA samples. Furthermore, no evidence for upregulation of
      KGF mRNA in skin tumors was obtained. The results are discussed in terms of the
      role of EGFr activation in skin carcinogenesis and the mechanisms for altered
      regulation of EGFr ligands.

PMID- 9655252
TI  - Immunological characterization of cell-surface and soluble forms of membrane type
      1 matrix metalloproteinase in human breast cancer cells and in fibroblasts.
AB  - Membrane type (MT) 1 matrix metalloproteinase (MMP) activates progelatinase A
      (pro-MMP-2), a type IV collagenase, on the cell surface of tumors; however, its
      function in breast cancer progression and metastasis is not fully understood. To
      examine the expression of MT1-MMP in breast cancer cells and fibroblasts, a
      specific rabbit antibody (Ab) directed against a unique synthetic peptide derived
      from the human MT1-MMP catalytic domain was produced, purified, and
      characterized. This Ab is not likely to cross-react with MT2-, MT3-, or MT4-MMP
      or any other MMPs. MT1-MMP expression and pro-MMP-2 activation were stimulated by
      concanavalin A in two human breast carcinoma cell lines (BT549 and MDA-MB-231)
      and in normal human fetal-lung fibroblasts (HFL-1) and were slightly upregulated
      by breast cancer cell-fibroblast interactions. Both pro-MT1-MMP in plasma
      membrane (63.4 kDa) and the soluble forms of the enzyme in culture medium (57.6
      and 25-30 kDa) were detected by immunoblot analysis, suggesting that cell-surface
      MT1-MMP exhibits an active conformation without the removal of its propeptide
      domain and that the mature enzyme is shed into the medium. In breast cancer
      cells, MT1-MMP and a recombinant catalytic domain of MT1-MMP were unable to
      activate pro-matrilysin, indicating that MT1-MMP is not a universal activator of
      all MMPs. MT1-MMP may play an important role in the invasive growth and spread of
      breast cancer cells by specifically activating pro-MMP-2 to cleave the connective
      tissue barrier. Furthermore, use of the specific Ab may aid in the investigation
      of the role of MT1-MMP in human tumors.

PMID- 9655253
TI  - Enhanced expression of anti-apoptotic proteins in human papillomavirus
      immortalized and cigarette smoke condensate-transformed human endocervical cells:
      correlation with resistance to apoptosis induced by DNA damage.
AB  - Apoptosis plays an important role in various biological processes including
      embryogenesis, differentiation, homeostasis, and oncogenesis. We have developed a
      system composed of primary human endocervical cells (HEN), HEN immortalized by
      human papillomavirus (HPV) type 16, and their counterparts subsequently
      malignantly transformed by cigarette smoke condensate (CSC). To understand the
      role of apoptosis in the multistep oncogenesis of human cervical cells, we
      examined the expression of apoptosis-associated proteins in our in vitro model
      system. The results showed no significant difference in the levels of apoptosis
      inducing proteins bak and bax among all the cell types examined. On the other
      hand, the levels of apoptosis-inhibiting proteins bcl-2, bcl-xL and BAG-1
      increased progressively after immortalization and transformation. The p53 protein
      level decreased in the HPV16-immortalized HEN and increased in one of two lines
      of the CSC-transformed HEN. Further, the increased levels of apoptosis-inhibiting
      proteins in the HPV16-immortalized and the CSC-transformed HEN correlated with
      progressively increased resistance of these cells to apoptosis induced by
      staurosporine or cisplatin. This study provided the first evidence that
      overexpression of apoptosis-inhibiting proteins is important for both multistep
      oncogenesis and resistance of human endocervical cells to apoptosis induced by
      DNA-damaging reagents.

PMID- 9655254
TI  - Estrogen upregulation of BRCA1 expression with no effect on localization.
AB  - Alterations in the expression of the breast and ovarian cancer susceptibility
      gene BRCA1 may contribute to the development of mammary and ovarian neoplasia.
      The sex-steroid estrogen modulates cell proliferation of normal and neoplastic
      breast and ovarian epithelial cells, but the role of estrogen regulation on the
      expression of BRCA1 remains to be defined. In this study, estrogen-regulated
      BRCA1 expression was examined in breast and ovarian cancer cells. Estrogen
      stimulated the proliferation of estrogen receptor (ER)-positive breast MCF-7, C7
      MCF-7, and ovarian BG-1 cells as well as the expression of the estrogen-inducible
      pS2 gene. This was concomitant with upregulation of BRCA1 mRNA (2.5- to 5.0-fold)
      and a 3- to 10-fold induction of BRCA1 protein (230 kDa). Cell fractionation
      studies localized the BRCA1 protein to the nucleus in both unstimulated and
      estrogen-stimulated cells. The antiestrogen ICI-182780 inhibited estrogen-induced
      cell proliferation, BRCA1 mRNA induction, and BRCA1 protein expression in ER
      positive cells. Conversely, estrogen did not influence expression of BRCA1 in HBL
      100 cells that lacked the estrogen receptor, although the constitutive levels of
      BRCA1 mRNA (but not protein) in these cells were 5- to 30-fold higher than in
      other breast and ovarian cancer cells. Secretion of the BRCA1 protein into the
      cell medium did not account for the discrepancy between the mRNA and protein
      levels in HBL-100 cells. Proliferation of HBL-100 cells was not affected by
      either estrogen or ICI-182780. Taken together, these data support a role for the
      steroid estrogen and the involvement of the estrogen receptor pathway in the
      modulation of expression of BRCA1. We therefore propose that stimulation of cell
      proliferation may be a prerequisite for upregulation of BRCA1 in breast and
      ovarian cancer cells.

PMID- 9655255
TI  - Formation of a stable src-AFAP-110 complex through either an amino-terminal or a
      carboxy-terminal SH2-binding motif.
AB  - The actin-filament-associated protein (AFAP-1 10) forms a stable complex with
      activated variants of the Pp60c-src (Src) non-receptor tyrosine kinase through
      SH2 and SH3 interactions. In this report, site-directed mutagenesis and a
      transient expression system that permits co-expression of activated pp60c-src
      (Src527F) and AFAP-110 in Cos-1 cells were used to identify the SH2-binding motif
      in AFAP-110. Four tyrosine residues, two in the amino terminus (Y93 and Y94) and
      two in the carboxy terminus (Y451 and Y453), were mutated to phenylalanine,
      significantly reducing overall steady-state levels of tyrosine phosphorylation
      and preventing Src527F from forming a stable complex with AFAP-110. These data
      indicate that the major sites for tyrosine phosphorylation are among these four
      tyrosine residues and that one or more of these tyrosines may function as an SH2
      binding motif. Mutagenesis of just two tyrosines in either the amino terminus
      (Y93/Y94) or in the carboxy terminus (Y451/Y453) to phenylalanine had only a
      modest effect on steady-state levels of tyrosine phosphorylation and was not
      sufficient to abrogate stable-complex formation. These data suggest that Src527F
      can form a stable complex with AFAP-110 through either of two independently
      functional SH2-binding motifs. Triple-tyrosine mutation demonstrated that Y93 was
      not significantly phosphorylated on tyrosine and would not facilitate stable
      complex formation, whereas Y94, Y451, and Y453 could be phosphorylated on
      tyrosine and would facilitate stable-complex formation. We hypothesize that
      Src527F and AFAP-110 interact through a multistep binding mechanism that may
      either extend interactions between Src527F and actin filaments or permit
      reorientation of Src527F on AFAP-110, which could facilitate the presentation of
      Src527F toward other signaling molecules.

PMID- 9655256
TI  - Neoplastic phenotype of gap-junctional intercellular communication-deficient WB
      rat liver epithelial cells and its reversal by forced expression of connexin 32.
AB  - Gap-junctional intercellular communication (GJIC) is involved in cellular growth
      control and is often reduced in neoplastic cells. In this study, four GJIC
      deficient rat liver epithelial cell lines (WB-aB1, WB-bA2, WB-cD6, and WB-dA2)
      were examined for altered growth and tumorigenicity in comparison with their GJIC
      competent parental cell line, WB-F344. WB-aB1 cells were also forced to express
      connexin 32 (Cx32) by transduction with a Cx32 cDNA retroviral expression vector
      to help determine whether the restoration of GJIC could reverse their neoplastic
      phenotype. WB-aB1 and WB-bA2 cells had faster population doubling times (PDTs)
      and higher saturation densities (SDs) than did WB-F344 cells. In contrast, the
      growth of WB-cD6 and WB-dA2 cells was not significantly different from that of WB
      F344 cells. WB-aB1 and WB-bA2 cells formed tumors in male F344 rats, but WB-cD6
      and WB-dA2 cells did not. After transduction of WB-aB1 cells with Cx32, four
      stable clones (WB-a/32-3, -8, -9, and -10) were isolated that had GJIC levels of
      5.2%, 44.5%, 69.8%, and 90.5%, respectively. The growth of poorly coupled clones
      3 and 8 was similar to that of parental WB-aB1 cells, but the growth of well
      coupled clones 9 and 10 was similar to that of WB-F344 cells. The tumorigenicity
      of WB-a/32-9 and WB-a/32-10 cells was also significantly lower than that of WB
      aB1 cells. Our results suggest that reduced GJIC contributes to neoplastic
      transformation of WB cells, that additional changes are necessary, and that
      restoration of GJIC by forced Cx32 protein expression can suppress the neoplastic
      phenotype of these cells.

PMID- 9655257
TI  - Interaction of retinoblastoma protein and D cyclins during cell-growth inhibition
      by hexamethylenebisacetamide in TM2H mouse epithelial cells.
AB  - To explore the regulation and function of D-type cyclins in breast cancer cells,
      the mouse mammary hyperplastic epithelial cell line TM2H was treated with 5 mM
      hexamethylenebisacetamide (HMBA), a polar differentiation factor. The resulting
      growth-inhibitory effect of HMBA was completely reversible and was analyzed in
      terms of percent cells in G1; association of D-type cyclins with cyclin-dependent
      kinase (cdk) 4 and cdk6; G1 kinase activity; association of retinoblastoma
      protein (pRb) and phosphorylated pRb with D-type cyclins; and association of
      p16INK4a, p15INK4b, and p27Kip1 with cdk4 and cdk6. Synchronized TM2H cells were
      examined at 0, 3, 5, 9, 12, and 24 h after exposure to 5 mM HMBA. Inhibition of
      DNA synthesis, as measured by thymidine uptake, was first observed at 5 h (40%)
      and peaked at 24 h (80%). Flow cytometry at 9 h showed treated cells to be in G1
      arrest. Western blot analysis showed weakly detectable cyclin D1 but readily
      detectable cyclin D2 and D3 proteins at 0 h; thereafter, cyclin D2 and D3 protein
      levels remained higher while cyclin D1 levels declined significantly in treated
      versus untreated cells. By 5 h (early G1), HMBA had markedly inhibited cdk4 and
      cdk6 kinase activity (67% and 75%, respectively) in treated versus untreated
      cells. By 9 and 12 h, pRb levels had increased 3.4-fold in treated versus
      untreated cells. At 5 h, cyclin D-associated pRb was totally hypophosphorylated
      in treated cells and hyperphosphorylated in untreated cells. The levels of pRb
      associated with cyclin D2 and D3 increased 2.89-fold and 4.6-fold, respectively,
      in treated versus untreated cells. At 5 h, treated cells showed a fivefold
      increase in cdk4-associated p27Kip1 and, at 9 h, a fourfold increase in cdk6
      associated p27Kip1 over control levels. In confirmation of these data, HMBA was
      found to inhibit the growth of Rb-positive Du/145Rb cells but not their Rb
      negative parental Du/145 cells. The data suggest that HMBA-induced growth
      inhibition is due to multifactorial mechanisms involving decreases in total
      cyclin D1 and inhibition of cdk4 and cdk6 kinase activities through elevation of
      levels of cdk4- and cdk6-associated p27Kip1 and concomitant increases in
      hypophosphorylated pRb and stable cyclin D2/pRb and cyclin D3/pRb complexes that
      help maintain pRb in a functional state.

PMID- 9655258
TI  - Expression of vascular endothelial growth factor and its receptors in the rat
      ventral prostate and Dunning R3327 PAP adenocarcinoma before and after
      castration.
AB  - BACKGROUND: Angiogenesis is important for prostate organogenesis and prostate
      cancer progression. It is not yet known whether androgens promote part of their
      control of prostate structure and function by influencing angiogenesis. The aim
      of this study was to explore the possible androgenic regulation of the angiogenic
      factor vascular endothelial growth factor (VEGF) and its receptors flt-1 and flk
      1/KDR in the rat ventral prostate (VP) and Dunning R3327 PAP adenocarcinoma.
      METHODS: RNA was prepared from VP and tumors of intact and castrated rats. VEGF,
      flt-1, and flk-1/KDR mRNA levels were determined using competitive RT-PCR.
      RESULTS: VEGF121, VEGF165, and VEGF189 together with flt-1 and flk-1/KDR mRNA
      were detected. The VEGF, but not flt-1 mRNA levels were significantly decreased
      in the VP after castration. The Dunning tumor expressed high levels of mRNA for
      VEGF and its receptors compared to the VP. The flt-1 mRNA level in the tumor
      increased after castration, while the VEGF mRNA levels were unchanged.
      CONCLUSIONS: Decreased mRNA expression of VEGF, but not flt-1, was found in the
      rat VP after castration. However, in the Dunning tumor, castration did not alter
      the expression of VEGF mRNA. Moreover, elevated levels of both mRNA for VEGF and
      its receptors relative to the VP were observed, indicating that the VEGF system
      may be important for Dunning tumor development.

PMID- 9655259
TI  - Effect of postnecrotic and alcoholic hepatic cirrhosis on development of benign
      prostatic hyperplasia.
AB  - BACKGROUND: The object of this study was to investigate the effects of hepatic
      cirrhosis on the development of benign prostatic hyperplasia and consequent
      effects on prostatic volume, serum prostate-specific antigen (PSA), and
      prostatism symptoms. METHODS: Sixty patients with postnecrotic cirrhosis and
      alcoholic cirrhosis at age 40 and over, and 20 voluntary subjects in the same age
      group with normal hepatic functions, were evaluated with prostatic volume
      calculation by transrectal ultrasound, symptom scoring according to American
      Urology Association (AUA) criteria, measurement of serum prostate-specific
      antigen (PSA), serum total testosterone (TT), free testosterone (FT), estradiol
      (E2), and calculation of E2/FT ratios, and the results were analyzed
      statistically by the Mann-Whitney U-test. RESULTS: Serum FT and TT levels were
      significantly lower in the hepatic cirrhosis group compared to the control group
      (P = 0.0000 and P = 0000, respectively). Though mean serum E2 level was a little
      higher in cirrhotic patients compared to controls, the difference was not
      significant; however, the higher E2/FT ratio in the cirrhotic group was
      statistically significant (P = 0.27 and P = 0.0002, respectively). In the
      cirrhotic group, the decrease in FT and TT levels was greater, as the disease
      advanced. While E2 and E2/FT ratio increase, correlate with poor prognosis, no
      statistically significant differences were found. Mean prostatic volume, serum
      PSA level, and total symptom score were significantly higher in the control
      group, compared to the cirrhotic group (P = 0.0001, P = 0.0006, and P = 0.002,
      respectively). Prostatic volume decreased parallel to severity of disease in
      cirrhotic patients. CONCLUSIONS: The main reason for the decrease in mean
      prostatic volume in cirrhotic patients compared to subjects in the same age group
      with normal hepatic functions was the decrease in serum FT and TT levels, and the
      secondary cause was the increase in E2/FT ratio, indicating estrogenic
      predominance.

PMID- 9655260
TI  - Expression of the extracellular matrix signaling molecule Cyr61 is downregulated
      in prostate cancer.
AB  - BACKGROUND: Prostate cancer (CaP) is one of the most common neoplasms in the USA
      and Europe. We used differential display PCR (DD-PCR) to identify genes related
      to the development of prostate cancer. METHODS: The RNA of 4 patients with
      untreated CaP was analyzed for differentially expressed genes. Using DD-PCR, we
      identified a downregulated cDNA-fragment in these prostate cancer cells. This
      fragment (N7) was cloned and further analyzed by CMRT-PCR, Northern-blot
      analysis, and in situ hybridization. RESULTS: Sequence analysis revealed that N7
      is identical to the 3'-untranslated region of the recently described immediate
      early gene Cyr61. Comparative multiplex RT-PCR with sequence specific primers
      showed that Cyr61 is downregulated in the tumor tissue of 7 out of 13 patients.
      By in situ hybridization we could demonstrate that the expression of Cyr61 is
      restricted to the epithelium of the prostate. Immunohistochemical analysis showed
      that Cyr61 protein could be found in the epithelium of normal prostatic tissue,
      whereas prostate cancer tissue showed a marked decrease of Cyr61 protein
      expression. CONCLUSIONS: Cyr61 is a member of the emerging family of
      extracellular signaling proteins and enhances the effect of bFGF. The changed
      pattern of expression Cyr61 might therefore contribute to the altered
      interactions between epithelial and stromal cells in prostate carcinoma.

PMID- 9655261
TI  - Fas-mediated apoptosis in seven human prostate cancer cell lines: correlation
      with tumor stage.
AB  - BACKGROUND: Apoptosis, or programmed cell death, can be mediated through an
      endogenous signaling pathway that emanates from a cell surface receptor known as
      Fas. Although best recognized for its role in the immune system, recent studies
      have also suggested a role for Fas in mediating apoptosis in the murine prostate.
      Little is known, however, regarding the role of Fas-signaling in the human
      prostate, and if this signaling pathway is abrogated in the development of
      prostate cancer (PC). METHODS: In the current study, seven human PC cell lines
      were evaluated for their sensitivities to Fas-mediated apoptosis, using both
      morphologic and flow cytometric methods. Fas expression by each cell line was
      quantitated by immunofluorescence, and gene expression of three putative
      inhibitory molecules was analyzed. RESULTS: The differential sensitivities of the
      cell lines to Fas-mediated apoptosis were found to correlate with the clinical
      stage of the parental tumors. Specifically, the three most sensitive cell lines
      were all derived from primary tumors, while the four most resistant cell lines
      were derived from distant metastases. Immunofluorescent analyses of the PC cell
      lines revealed that the observed resistance to apoptosis was not due to reduced
      expression of membrane-bound Fas. Likewise, this resistance did not correlate
      with increased gene expression of the inhibitory molecules FAP-1, ICE epsilon,
      and Ich-1S. CONCLUSIONS: Our results using established PC cell lines support
      previous studies with prostatic tissue specimens, and suggest that the normal,
      differentiated prostatic epithelium, as well as locally invasive PCs, have the
      potential to undergo Fas-mediated apoptosis. Conversely, these studies suggest
      that metastatic PCs have a reduced apoptotic potential that is mediated by a
      novel mechanism.

PMID- 9655262
TI  - Establishment of prostatic cell line "Pro9ad" from a p53-deficient mouse.
AB  - BACKGROUND: We demonstrated that p53-deficiency is sufficient for immortalization
      of fetal uterine cells. In the present study, we further extended our previous
      observations to prostate tissues from a young p53-deficient adult mouse. METHODS:
      Cell lines were established from the ventral prostate of a p53-deficient male
      mouse and maintained in medium containing 10% heat-inactivated fetal calf serum
      supplemented with insulin (10 microg/ml), transferrin (10 microg/ml), cholera
      toxin (10 ng/ml), and selenium (10(-8) M). RESULTS: Pro9ad, one of the lines
      established, exhibits a typical epithelial morphology in culture. Despite the
      possession of androgen receptors, the growth of Pro9ad was not stimulated by
      5alpha-dihydrotestosterone. Hepatocyte growth factor (HGF) slightly stimulated
      proliferation, whereas fibroblast growth factor-1 (FGF-1), keratinocyte growth
      factor (KGF), and platelet-derived growth factor AB (PDGF-AB) had no stimulating
      effect on growth. However, FGF-2, epidermal growth factor (EGF), and insulin-like
      growth factor-1 (IGF-1) accelerated proliferation in a dose-dependent manner. EGF
      and IGF-1 additively stimulated growth. CONCLUSIONS: These results suggest that
      Pro9ad shares characteristics in common with primary prostatic epithelial cells
      despite p53-deficiency, and that p53-deficiency alone allows establishment of
      clonal cell lines of the prostate epithelium. Furthermore, the prostates of p53
      deficient mice are useful sources for obtaining cell lines.

PMID- 9655263
TI  - Stromal and epithelial cells of the canine prostate express parathyroid hormone
      related protein, but not the PTH/PTHrP receptor.
AB  - BACKGROUND: Parathyroid hormone-related protein (PTHrP), a principal factor in
      the pathogenesis of humoral hypercalcemia of malignancy, is also widely expressed
      in many normal tissues, including human prostatic epithelial cells. The role of
      PTHrP in the prostate is not known, but may include regulation of cell growth and
      differentiation or calcium secretion into prostatic fluid. The dog is a valuable
      animal model for human prostatic diseases. The objective was to investigate the
      expression of PTHrP and the PTH/PTHrP (type 1) receptor in primary cultures of
      canine stromal and epithelial prostatic cells. METHODS: Expression and secretion
      of PTHrP and the PTH/PTHrP receptor was measured in homogeneous primary cultures
      of canine prostatic stromal and epithelial cells using immunohistochemistry,
      Northern blots, radioimmunoassay, RT-PCR, and receptor stimulation assays.
      RESULTS: Epithelial and stromal cells expressed and secreted abundant PTHrP, but
      PTH/PTHrP receptor expression was not detected in either cell type. CONCLUSIONS:
      PTHrP expression by stromal and epithelial prostatic cells and the absence of the
      PTH/PTHrP (type I) receptor suggest that some functions previously proposed for
      PTHrP in the prostate are unlikely. The separation procedure presented is a
      valuable tool for studying the role and regulation of PTHrP in the prostate.

PMID- 9655264
TI  - Detection of telomerase activity in prostate needle-biopsy samples.
AB  - BACKGROUND: Telomerase in an enzyme ribonucleoprotein responsible for cell
      immortality and oncogenesis. Telomerase activity has been detected in most
      cancers, including prostate cancer. To verify whether the detection of telomerase
      in prostate needle biopsy samples could have diagnostic value, we blindly assayed
      telomerase activity in samples from patients who were clinically suspected of
      having prostate cancer. METHODS: A total of 183 prostate biopsy samples was
      obtained from 63 patients who were suspected of having prostate cancer.
      Telomerase activity was determined by polymerase chain reaction (PCR)-based
      telomeric repeat amplification protocol (TRAP) assay. An internal telomerase
      assay standard (ITAS) was used in this study to distinguish false negatives.
      RESULTS: Telomerase activity was detected in 17 of 19 (89.5%) patients with
      prostate cancer (chi(2) test, P < 0.005). In 39 of 42 (92.9%) biopsy samples from
      these 19 prostate cancer patients, confirmed histologically as prostate cancer,
      telomerase activity (chi(2) test, P < 0.005) was detected. Meanwhile, we also
      found one false-positive sample. In contrast, all of 44 normal or benign prostate
      disease patients (124 biopsy specimens) were telomerase-negative. We also
      revealed that poorly differentiated prostate cancer often expresses a high level
      of telomerase activity. The area of cancer tissue in biopsy specimens was not
      associated with relative telomerase activity. CONCLUSIONS: This study suggests
      that determination of telomerase activity in prostate needle-biopsy samples might
      be a useful tool for detecting prostate cancer.

PMID- 9655265
TI  - Induction of prostate tumor-specific CD8+ cytotoxic T-lymphocytes in vitro using
      antigen-presenting cells pulsed with prostatic acid phosphatase peptide.
AB  - BACKGROUND: Most strategies in cancer immunotherapy are aimed at the induction of
      a strong cellular immune response against the tumor. Particularly, CD8+ T
      lymphocytes have been proven in multiple animal models to be critical for the
      eradication of solid tumors. METHODS: We used a population of peripheral blood
      derived antigen-presenting cells (APC), containing dendritic cells (DC), to
      generate prostate tumor-specific CD8+ T cells. Selected peptides from prostatic
      acid phosphatase (PAP), a prostate tissue-specific antigen, were shown to bind
      HLA-A2. A high-affinity peptide was used to generate peptide-specific CD8+
      cytolytic T lymphocytes (CTL) from the peripheral blood of healthy donors.
      RESULTS: The obtained PAP-peptide-specific CTL lysed peptide-coated target cells,
      vaccinia-infected target cells, and HLA-A2-positive prostate-tumor cells in vitro
      in an antigen-specific manner. CONCLUSIONS: Our results indicate that CTL
      precursors to the PAP gene product exist and could be potentially recruited to
      elicit an antitumor response. Thus, PAP is a suitable antigen for inclusion in
      prostate cancer vaccines.

PMID- 9655266
TI  - Family not Faustian values.

PMID- 9655267
TI  - An evaluation of the effects of semirigid cervical collars in patients with
      severe closed head injury.
AB  - The use of a semirigid cervical collar has been recommended to prevent further
      cervical spine injury in the management of trauma patients. These cervical
      collars are kept on obtunded patients for prolonged periods. We assessed the
      incidence of cervical collar related decubiti in patients with severe closed head
      injury (SCHI). We also assessed the utility of fluoroscopy in clearing the
      cervical spine of patients with SCHI. A retrospective chart review was performed
      on 52 consecutive patients with SCHI at a community hospital-based Level II
      trauma center over an 8-month period. Thirteen of 34 patients (38%) who survived
      >24 hours after admission developed decubiti related to the cervical collar. The
      patients who developed decubiti had a significantly greater duration of cervical
      collar placement (21.15 +/- 0.99 days) as compared with patients who did not
      develop decubiti (4.42 +/- 0.79 days; P = 0.001). Eight patients had their
      cervical spine assessed for ligamentous injury by bedside fluoroscopy. All eight
      patients had early collar removal; none of these patients developed decubiti.
      Patients with SCHI with semirigid cervical collars kept in place for prolonged
      periods of time are at risk for developing decubiti. Fluoroscopy in addition to
      standard radiographs may "clear" the cervical spine and allow early removal of
      these collars.

PMID- 9655268
TI  - Autologous closure of giant abdominal wall defects.
AB  - Split-thickness skin graft coverage of exposed and granulating intestines within
      large abdominal wall defects provides a life-saving permanent biologic dressing.
      The resultant abdominal wall defect often is closed with mesh, which may infect
      and fistulize. This report describes bilateral advancement flaps of the external
      oblique and recti muscles in 11 patients treated over 3 years. The defects, which
      averaged 16 x 24 cm, were due to necrotizing fasciitis subsequent to trauma with
      bowel perforation (3 patients), multiple ventral herniorrhaphies (2 patients),
      perforated diverticulitis (4 patients), and perforated peptic ulcer (2 patients).
      Eight patients were initially treated elsewhere where closure was achieved by
      split-thickness skin graft in five patients or mesh in 3 patients; 3 developed
      enterocutaneous fistulae and were transferred for closure while receiving long
      term antibiotic and total parenteral nutrition therapy. All 11 patients had
      successful primary closure. The 8 patients operated on electively had primary
      healing; 2 developed seromas. Two of the three patients operated on urgently
      developed superficial wound infections; both healed by second intent without
      compromise of the primary closure. The following conclusions can be drawn: (1)
      the linea alba survives despite necrotizing fasciitis, (2) a tension-free primary
      closure is feasible; (3) morbidity is minimal, and (4) the long-term result is
      excellent.

PMID- 9655269
TI  - The changing face of mesenteric infarction.
AB  - Intestinal infarction remains a devastating event despite improvements in
      clinical recognition as well as diagnostic and therapeutic modalities. Recent
      changes in the etiology of this disease have not been examined. A retrospective
      review of 121 consecutive patients over a 6-year period was undertaken. Twenty
      three patients died without operation, and mortality in the remaining 98 patients
      was 50 per cent. The only significant predictor of mortality was an elevated
      serum lactate at the time of diagnosis. Thirty-one patients (26%) developed
      infarction while hospitalized for another disease process; excluding patients
      with obstruction as the etiology of infarction caused this number to rise to 39
      per cent. Nonocclusive mesenteric infarction was the most common disease process.
      The increased incidence of nonocclusive mesenteric infarction is likely due to
      the development of intestinal ischemia in already systemically ill patients.
      Nearly half of all cases of intestinal infarction due to nonobstructive causes
      develop in already hospitalized patients. The development of unexplained acidosis
      in a postoperative or critically ill patient should prompt a search for a
      reversible cause of mesenteric ischemia. Intestinal infarction may represent
      another example of the multisystem organ failure syndrome.

PMID- 9655270
TI  - Role of prophylactic antibiotics for tube thoracostomy in chest trauma.
AB  - The objective of this study was to evaluate the efficacy of antibiotic
      prophylaxis in association with tube thoracostomy for chest trauma patients with
      Injury Severity Scores of 9 or 10. A double-blind randomized clinical trial of
      patients requiring tube thoracostomy was performed at an urban Level 1 trauma
      center. All patients included in this series were patients with Injury Severity
      Scores of 9 or 10 (hemothorax/pneumothorax) who suffered isolated chest trauma
      secondary to blunt or penetrating trauma. Before chest tube placement, 139
      patients (34 blunt trauma, 105 penetrating trauma) were blindly randomized to
      Group A (71 patients) for which they received 1 g cefazolin intravenously every 8
      hours or Group B (68 patients) for which they received a placebo intravenously
      every 8 hours. Antibiotic or placebo was administered before chest tube insertion
      and continued until the time of chest tube removal. The majority of patients
      underwent chest tube placement in the emergency room with a small number of
      delayed pneumothoraces (4 patients) treated after admission. In the 71 patients
      receiving antibiotic, 7 complications (1 pleural effusion, 2 chest tube
      reinsertions, 4 additional chest tubes) occurred, none of which were infectious.
      In the 68 patients receiving placebo, 7 complications (2 empyemas, 2 pneumonias
      with effusions, 1 pleural effusion, 2 chest tube reinsertions) occurred, 4 of
      which were infectious and required antibiotic intervention (P = 0.05, Fisher's
      exact test). This study showed that patients receiving antibiotics have a
      significantly reduced incidence of infectious complications and suggests that
      patients who undergo tube thoracostomy for chest trauma would benefit from
      administration of prophylactic antibiotics.

PMID- 9655271
TI  - Endoscopic retrograde cholangiopancreatography in a general surgery training
      program.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) is one of the most complex
      procedures performed by endoscopists. ERCP has been performed primarily by
      gastroenterologists. There have been no reports in the literature regarding ERCP
      training within the framework of a general surgery residency program. The purpose
      of this study was to review ERCPs performed by surgical attendings and resident
      staff during a 6-year period and compare the success and complication rates with
      those found in published gastroenterological series. There were a total of 193
      ERCPs performed on 171 patients for a success rate of 82.4 per cent and a
      complication rate of 6.7 per cent. A resident was the primary endoscopist in 51
      procedures, with 42 (82.4%) successes and 2 complications (3.9%). There were no
      significant differences noted between our series and national complication rates,
      and between attending and resident procedures (P < 0.05, Chi-square analysis).
      This study has shown that surgical endoscopists can perform ERCP with success
      rates over 80 per cent, the currently regarded standard of expertise. The
      complication rates for these ERCPs were lower than accepted complication rates
      cited in current gastroenterological series. The results of this study support
      the hypothesis that ERCPs can be performed safely in a surgical residency.

PMID- 9655272
TI  - Laser ablation of complex perianal fistulas preserves continence and is a rectum
      sparing alternative in Crohn's disease patients.
AB  - A 20-year review of the inflammatory bowel disease surgical database of the
      author was analyzed for Crohn's disease (CD) patients who had a surgical approach
      to perianal fistula disease (PAD). Of 333 patients with CD operated between July
      1977 and February 1997, 51 had procedures for PAD (15.3%), and 7 of these
      patients had laser ablation of severe, debilitating complex PAD (13.7%). These
      patients have traditionally been treated by diverting ileostomy or proctectomy
      with permanent diversion. Others have advocated conservative management with long
      term antibiotics, staged operations, and insertion of multiple loose setons to
      promote drainage. This technique was adapted from the laser procedure now
      advocated for severe hydradenitis suppurativa. The hand-held CO2 laser was used
      to unroof all fistulas external to the external sphincter. Fistulas were
      identified by probing. Infected granulation tissue was removed by laser ablation
      until normal fat or muscle was revealed. Intersphincteric abscesses were
      unroofed, and a single seton was placed around the external sphincter for all but
      submucous fistulas. Patients were usually operated as outpatients with pain
      control effected with oral and transnasal agents. A laparoscopically performed
      temporary diverting ileostomy was used in one early patient in the series.
      Patients were followed, and progress was documented by physical examination and
      photographs. Quality of life was assessed. All patients improved remarkably from
      their preoperative state. The 4 patients in the group operated more than 1 year
      before this review have all demonstrated complete healing. The three more recent
      patients are in various stages of healing. Continence was preserved in 7 of 7
      patients. No patient has required rectal excision. Recurrence thought to be
      related to associated hydradenitis has occurred in 1 patient. Laser ablation is a
      valuable technique in the management of patients with severe, debilitating
      complex PAD complicating CD. It effectively eradicates the septic tracks and
      pockets while preserving sphincter function. It obviates the need for diversion
      with or without proctectomy.

PMID- 9655273
TI  - Laparoscopic herniorrhaphy in the geriatric population.
AB  - Laparoscopy has brought controversy to herniorrhaphy, particularly in the
      elderly. We reviewed our experience with this technique in patients older than 65
      years at a single teaching institution. Data include demographics, American
      Society of Anesthesiologists (ASA) class, operative time, hernia type, type of
      repair, hospital stay, and complications. A telephone questionnaire was used to
      assess return to normal activity, recurrence, and reason for choosing the
      laparoscopic approach. From March 1992 through March 1996, 110 of 328 patients
      were eligible. Mean age was 73 +/- 5.6 years; 34 patients had bilateral and 20
      had recurrent hernias; 73 patients (66.4%) were ASA-2, and 22 (20%) were ASA-3.
      The extra-abdominal and transabdominal preperitoneal approaches were used in 64
      and 46 patients, respectively; mean operative time was 87.9 +/- 34 minutes. The
      overall complication rate was 15 per cent, with 71 per cent of these being
      urinary retention. Patients were discharged the same day (59%) and at 1 day
      (33%). Follow-up was available in 84.5 per cent. Recurrence rate was 9.7 per
      cent, which was not significantly influenced by complication rate, hernia repair
      type, or ASA class. Median return to normal activity was 7 days. ASA
      classification correlated with hospital stay (P = .02), but not with
      complications, recurrence, or return to normal activities (P = not significant).
      Laparoscopic herniorrhaphy appears safe in the elderly.

PMID- 9655274
TI  - Bile duct injuries during laparoscopic cholecystectomy: a community's experience.
AB  - Reports of bile duct injuries are from tertiary care institutions and, therefore,
      may not report the spectrum of management that these patients receive in the care
      of these injuries. From June 14,1990 (the first operation) to June 30, 1995, 2654
      laparoscopic cholecystectomies (LCs) were reviewed at this community hospital
      medical center to determine risk factors contributing to the etiology of these
      injuries, time and symptoms at presentation, duration of illness, and management
      of these injuries. None of the 13 general surgeons practicing during this time
      period had laparoscopic training in a general surgical residency. There were six
      major bile duct injuries (0.25%), of which five were available for further
      review. All occurred in women with cholelithiasis and chronic cholecystitis. Two
      operations were routine and two were associated with biliary tract anomalies. In
      two patients, the injuries were detected at LCs and definitive biliary-enteric
      anastomoses were performed immediately. Three patients presented at 2, 15, and 42
      days after LC. In two patients, one or more operative procedures were performed
      before definitive repair and these patients were referred to tertiary care
      centers. One patient was managed with sequential CT-guided drainage catheters
      after attempted closure of the defect. The length of illness for these five
      patients was 8, 69, 348, 402, and 435 days with a follow-up of 245, 345, 531,
      575, and 1088 days. Laparoscopic experience before injury by the operating
      surgeon was 3, 26, 35, 77, and 333 operations. Major biliary tract injuries
      occurred during routine cholecystectomy, length of illness was substantial for
      most patients, and biliary-enteric anastomosis was definitive for four of the
      five patients. The operating surgeons' "learning curve" did not seem as important
      as in other studies.

PMID- 9655275
TI  - The changing face of cholecystectomy.
AB  - Previous reports in selected patient populations have noted an increase in the
      number of cholecystectomies since the introduction of laparoscopic
      cholecystectomy. To assess the impact of laparoscopic cholecystectomy in a more
      general population, 6473 consecutive cholecystectomies from 7/1/86 to 6/30/95
      were reviewed to assess changes in rate of cholecystectomy, diagnosis leading to
      cholecystectomy, and general patient demographics. During the 9-year period, the
      number of cholecystectomies increased from 618 to 800 per year (29%; P < 0.002).
      Even more striking was the redistribution of cholecystectomies performed for
      acalculous disease (P < 0.0001), with the rate of increase more than doubling for
      each individual diagnosis (biliary dyskinesia, 348%; acute acalculous
      cholecystitis, 139%; chronic acalculous cholecystitis, 138%). When comparing
      patient characteristics, there was a significant increase in the number of
      cholecystectomies performed on females when compared with males. When compared
      with other races, whites underwent cholecystectomy for chronic acalculous
      cholecystitis at a higher rate (120%; P < 0.0003). The introduction of
      laparoscopic cholecystectomy was followed by a dramatic increase in
      cholecystectomies performed for acalculous disease and less so for
      cholelithiasis. Accompanying the increase were significant alterations in patient
      demographics. The study provides indirect evidence for lowering thresholds and
      changing indications with reasons for the increases yet to be determined.

PMID- 9655276
TI  - Measuring gastroesophageal reflux disease: relationship between the Health
      Related Quality of Life score and physiologic parameters.
AB  - The Gastroesophageal Reflux Disease-Health-Related Quality of Life (GERD-HRQL)
      scale is a reliable, valid, responsive, and practical measure of symptom severity
      in patients with GERD. This type of scale is needed to determine effects of
      treatments and their comparison. This study defines the relationship between the
      GERD-HRQL score and the physiologic parameters of esophagogastroduodenoscopy,
      esophageal manometry, and 24-hour esophageal pH monitoring. Fifty-five patients
      referred for surgical evaluation of GERD answered the GERD-HRQL, a nine-item
      ordinal-scaled questionnaire. They were evaluated with
      esophagogastroduodenoscopy, esophageal manometry, and 24-hour pH monitoring. The
      relationships among these results were determined by linear regression analysis.
      There were no correlations between lower esophageal sphincter (LES) and any of
      the pH monitoring parameters (all r < 0.25, P > 0.2), esophagitis grade (r = 
      0.21, P = 0.2), nor any individual GERD-HRQL item score nor total score (all r <
      0.2, P > 0.11). There were correlations between all the pH monitoring parameters
      and esophagitis grade (all r > 0.6, P < 0.001), but not with any of the GERD-HRQL
      item scores or total score (r < 0.3, P > 0.15). Six of the nine items scores and
      the total GERD-HRQL score correlated with esophagitis grade (all r > 0.4, P <
      0.01). LES pressure is a poor indicator of symptom severity, the amount of
      reflux, and esophageal mucosal damage. pH monitoring-measured reflux and GERD
      HRQL-measured symptom severity correlate well with mucosal damage. If the goals
      of GERD treatment are to relieve symptoms and reverse mucosal damage, the GERD
      HRQL score and 24-hour pH monitoring are better outcome measures than the LES
      pressure. In an era of cost containment, the GERD-HRQL may be an adequate outcome
      measure.

PMID- 9655277
TI  - A prospective experience with selective cholangiography.
AB  - A prospective study of patients with symptomatic cholelithiasis was undertaken to
      determine the effectiveness of identifying clinically significant
      choledocholithiasis with selective cholangiography. Between 1991 and 1995, 262
      patients presented to the senior author (K.W.M.) with acute or chronic
      cholecystitis. Sixteen patients had a preoperative endoscopic retrograde
      cholangiopancreatography (ERCP) for an elevated alkaline phosphatase or total
      bilirubin greater than twice the normal value or an ultrasound finding suspecting
      choledocholithiasis. Ten of the ERCP patients had choledocholithiasis, with eight
      patients having successful clearance by ERCP. Ninety other patients had
      intraoperative cholangiography for abnormal serum liver biochemistries, a history
      of jaundice or pancreatitis, or a dilated common bile duct (CBD) (>6 mm) on
      ultrasound. Fourteen of the intraoperative cholangiography patients and the two
      remaining ERCP patients had choledocholithiasis requiring CBD exploration for
      clearance of their stones. There were no false-positive cholangiograms, and there
      were no bile duct injuries in this series. With 100 per cent follow-up of at
      least 2 years, only one patient required ERCP clearance of a retained CBD stone
      13 months after cholecystectomy. The positive predictive value and the negative
      predictive value for the selective cholangiography criteria are 23 per cent and
      99 per cent, respectively. In conclusion, clinically significant
      choledocholithiasis can be found effectively with selective cholangiography.
      Also, utilizing selective cholangiography reduces the number of routine
      cholangiograms by 60 per cent.

PMID- 9655278
TI  - The association of intra-abdominal infection and abdominal wound dehiscence.
AB  - Concurrent infection is a risk factor for abdominal wound dehiscence. We reviewed
      our experience with fascial dehiscence to determine the incidence and to identify
      prognostic factors for associated intra-abdominal infection. Over a 7-year
      period, 107 patients with abdominal wound dehiscence were identified. Seventeen
      were managed nonoperatively, and 90 underwent exploratory laparotomy, 43 of whom
      had no intra-abdominal pathology and 47 of whom had intra-abdominal infections.
      Demographic factors, comorbid diseases, and potential indicators of systemic
      infection did not distinguish patients with intra-abdominal infection from those
      without. Patients with an intra-abdominal infection were more likely to have
      undergone an emergency operation (74% vs 48%; P < 0.02), an operation on the
      colon (55% vs 25%; P < 0.005), or an operation with a higher wound classification
      (P < 0.02). Mortality was higher in patients with intra-abdominal infection than
      in those without (44% vs 20%; P < 0.02). Wound dehiscence after emergent
      operations, and operations with a higher wound classification, especially those
      involving the colon, should raise concern for intra-abdominal infection. Thorough
      abdominal exploration should be performed at the time of dehiscence repair.
      Before nonoperative management is chosen, intra-abdominal infection should be
      excluded.

PMID- 9655279
TI  - Gamma-probe-guided resection of the sentinel lymph node in breast cancer.
AB  - Regional lymph node metastases in patients with breast cancer have fundamental
      staging, prognostic, and treatment implications. Classically, axillary lymph node
      sampling requires a dissection under general anesthesia. The concept that a
      primary, or sentinel, lymph node is the first node to receive drainage from a
      tumor has been established in patients with malignant melanomas using
      radiolabeled tracers and vital dyes. This study proposed two hypotheses: (1)
      radiolabeled sentinel lymph nodes can be identified in most patients with breast
      cancer, and (2) radiolabeled sentinel lymph node biopsy accurately predicts
      axillary lymph node metastases in those patients. Patients with operable breast
      cancer had Tc-99 sulphur colloid injected around their breast tumors 1-6 hours
      preoperatively. Patients underwent gamma probe identification of sentinel lymph
      nodes that were biopsied. All patients underwent axillary lymphadenectomy in
      conjunction with lumpectomy or mastectomy. Fifty female patients ages 26 to 90
      years underwent lumpectomies with axillary dissections (40 patients) or modified
      radical mastectomies (10 patients). Sentinel lymph nodes were identified in 42 of
      50 patients (84%). Eight patients (16%) had metastases to the axillary lymph
      nodes. In 7 patients, sentinel lymph nodes correctly predicted the status of the
      axillary nodes. There was one false negative result. A total of 550 lymph nodes
      were resected for an average of 11.2 nodes per patient. Sentinel lymph node
      scintigraphy and biopsy accurately predicted the axillary lymph node status in 41
      of 42 patients (98%). Scintigraphy can identify sentinel lymph nodes in a large
      majority of patients. Sentinel lymph node biopsy is an accurate predictor of
      axillary lymphatic metastases.

PMID- 9655280
TI  - Can scintimammography reduce "unnecessary" biopsies?
AB  - 99Tc-sestamibi prone scintimammography (SMM) is a new, noninvasive method of
      imaging breast tumors. A pilot study has suggested that SMM increases the
      specificity of mammography, and that SMM could be used as an adjunct to
      mammography to reduce the number of mammographically indicated biopsies. The goal
      of this study was to further evaluate the efficacy of SMM in diagnosing or
      excluding breast carcinoma. This was a prospective case series with each patient
      serving as her own control. All subjects who had an abnormal mammogram, a
      palpable breast mass, or both were eligible for inclusion. All patients underwent
      breast examination, conventional mammography, SMM, and breast biopsy. Of the 81
      women originally enrolled, 79 women with 80 lesions completed the study. SMM
      produced the following results: a sensitivity of 81 per cent, a specificity of 81
      per cent, a positive predictive value of 61 per cent, and a negative predictive
      value of 92 per cent. These values were significantly lower than the pilot study
      results at a power of 80 per cent and P = 0.05. Our results indicate that SMM
      does not increase the specificity of conventional mammography and has a low
      negative predictive value. We would not recommend it as a screening technique to
      avoid biopsy.

PMID- 9655281
TI  - Thyroid reoperations: indications and risks.
AB  - Thyroid reoperations can be technically difficult and associated with an
      increased risk of complications. To determine the indications for reoperations
      and the risk of postoperative complications with these procedures, records of 362
      patients undergoing thyroidectomy by a single surgeon (R.A.P.) were reviewed.
      Thirty-two patients had a reoperation. The group consists of 21 women and 11 men
      with an average age of 55 years (range, 31-79). Twenty-four patients had 1 prior
      operation, and 8 patients had 2 or more. We performed 4 of the initial
      operations, and 28 were done by surgeons at other centers. Fourteen reoperations
      were done for symptomatic multinodular goiter (MNG), and 5 because of a change in
      the histologic diagnosis from benign to cancerous. The remainder were for further
      treatment of malignancy. The most common operation was completion thyroidectomy
      (31). In 3 patients, either unilateral or bilateral modified radical neck
      exploration was performed. One patient required median sternotomy. One subtotal
      thyroidectomy was also performed. Recurrent laryngeal nerve injury occurred in 2
      patients. It resolved in 1 patient but was permanent in another, who had 3
      operations for MNG. One of the 2 patients with preoperative unilateral vocal cord
      paralysis had return of function after removal of a substernal goiter. The other
      had a permanent nerve injury from the original surgery. Three patients had
      postoperative hypocalcemia (calcium <8.0 mg/dL). This resolved in all patients
      within 1 to 6 months. One patient who had a third operation for MNG had
      postoperative hemorrhage necessitating tracheostomy for airway control. Another
      patient developed a seroma that resolved within 2 months. We conclude that
      reoperations are indicated for both benign and malignant thyroid disease. Because
      they carry a higher risk of complications, every effort should be made to avoid
      them by performing definitive initial treatment.

PMID- 9655282
TI  - Inadequate documentation and resection for gastric cancer in the United States: a
      preliminary report.
AB  - Patients entered into Southwest Oncology Group gastric adjuvant protocol INT 0016
      (SWOG 9008) after a "curative" gastric resection were assessed to determine
      practice patterns of more than 300 surgeons nationwide who performed "curative"
      gastric resections for 453 gastric cancer patients. The most common gastric
      resection performed was distal in 256 patients, proximal in 118, and total in 79.
      Extragastric organs resected were omentum (285), spleen (59), pancreas (18), and
      bowel (17). The extent of lymphadenectomy as staged by Japanese rules was 246
      (54.2%) D0 resections, 173 (38.1%) D1 resections, 28 (6.2%) D2 resections, and 7
      (1.5%) D3 resections. Staging of the cancer was poorly documented, with no
      statement made regarding the status of the primary cancer in 6 per cent, liver in
      10 per cent, lymph nodes in 17 per cent, and omentum in 17 per cent. The greater
      the lymph node clearance, the greater the chance of resecting to a level of
      negative lymphatics, given that 45 per cent of nodes were involved when 10 or
      less were removed, whereas only 17 per cent were positive when more than 40 were
      cleared. The lack of adequate clearance of lymph nodes and poor documentation of
      tumor stage suggests that a more regimented surgical approach to this uncommon
      cancer is required.

PMID- 9655283
TI  - Preoperative versus postoperative chemoradiation for patients with resected
      pancreatic adenocarcinoma.
AB  - Two groups of patients with adenocarcinoma of the pancreas treated with either
      preoperative chemoradiation (preop CTRT) or postoperative chemoradiation (postop
      CTRT) were retrospectively analyzed for various treatment-related parameters.
      Between November 1986 and October 1996, a total of 70 patients with pancreatic
      adenocarcinoma were enrolled into preop CTRT protocols at our institution. Twenty
      five patients with adenocarcinoma of the head of the pancreas underwent
      pancreaticoduodenectomy with curative intent. After the closure of the preop CTRT
      protocols, we had the opportunity to perform 23 pancreatic resections without
      preop CTRT. After surgery, these patients were advised to undergo CTRT. These two
      groups of patients were therefore selected consecutively, dependent only on the
      time of referral and no other bias. These two cohorts of patients are compared
      for various intraoperative parameters, length of hospital stay, pathologic
      findings, time to recurrence, and survival. Mean age was 65 and 66 years in the
      preop and postop CTRT groups, respectively. Sex distribution was almost equal.
      Treatment breaks resulting in greater than 1 week delay in the radiotherapy
      occurred in 2 (8%) of 25 patients in the preop CTRT group (myelotoxicity in 1
      case and biliary sepsis in 1 case), whereas no treatment breaks >1 week occurred
      in those receiving postop CTRT. Eleven patients in preop CTRT had grade 3 or 4
      toxicity, whereas none was noted in those with postop CTRT. There was one
      postoperative death in the preop CTRT group and none in the postop CTRT group.
      Mean time to the start of CTRT was 45 days (range, 20-66 days) after
      pancreaticoduodenectomy. Delay of >60 days to the onset of CTRT occurred in 2
      (22%) patients and was attributable to patient delays in time to recover from
      surgery or patient noncompliance. Furthermore, 5 of 23 patients (22%) in the
      postop CTRT group did not receive treatment for various reasons. Average
      estimated operative blood loss was 1933 mL (median 1550) and 1060 mL (median
      1000) for preop and postop CTRT groups, respectively. Mean length of operation
      was 488 minutes (median 480) and 486 minutes (median 480). Median length of
      postoperative stay was 22 and 20 days (ranges, 9-144 and 10-38). Pathological
      findings in the resected specimens showed significantly fewer involved nodes in
      the preop CTRT group (28 vs 87%; P = 0.0006), whereas similar numbers of
      nodes/patient were counted in each group (14 vs 22, P = 0.11). More negative
      resection margins were observed in the preop CTRT group (28 vs 56%; P = not
      significant). A significantly greater amount of fibrosis replacing the tumor was
      observed in the preop CTRT group (70 vs 40%; P = 0.0001). There were no
      significant survival differences observed (median 20 months vs 25 months; P =
      0.48), in follow-up that ranged from 4 to 76 months (median 44 months for
      surviving patients) for the preop group and 4 to 40 months (median 16 months for
      surviving patients) for those with postop CTRT. Local failure either alone or as
      a component of distant failure occurred in 16 per cent (4 of 25 patients) with
      preop CTRT and 16.6 per cent (3 of 18) with postop CTRT. Analysis of differences
      between those treated with preoperative and postoperative CTRT demonstrates
      similarity in toxicity and effects. However, 22 per cent of patients intended for
      postoperative therapy did not receive treatment.

PMID- 9655284
TI  - Unilateral parathyroid exploration.
AB  - Unilateral neck exploration (UNE) for primary hyperparathyroidism can be done
      with the same excellent results as bilateral neck exploration (BNE) with
      decreased operative time and postoperative complications with a good preoperative
      localization study. One hundred six charts were reviewed retrospectively in
      patients operated on between May 1989 and October 1996 with primary
      hyperparathyroidism. Seventy-seven of these patients had preoperative ultrasounds
      (US) performed by a radiologist interested in parathyroid ultrasonography. UNE
      was performed if the operative findings were consistent with the US and a normal
      gland was identified on the same side. If a normal gland was not identified on
      the initial side or there was a question of hyperplasia a BNE was performed.
      Forty-six of the 77 patients had UNE, and 31 had BNE. Sixty-nine of these
      patients were found to have accurate US. Based on these results there is a 90 per
      cent accuracy rate for US performed by an interested radiologist. Comparing
      operative times between patients with UNE and BNE, there was a statistical
      difference (P = 0.001). Complications were also recorded in each group. Patients
      with UNE had a 22 per cent complication rate, whereas patients with BNE had a 45
      per cent complication rate. This difference was statistically significant (P =
      0.04) (Fisher's exact test). The majority of complications were asymptomatic and
      symptomatic hypocalcemia. Two patients in the BNE group experienced transient
      hoarseness. The advantages of UNE include reduced morbidity, decreased operative
      time and avoidance of scarring in the contralateral neck. In the total study
      population (n = 106), 99 patients (93.4%) had a single adenoma. An accurate,
      noninvasive, low-cost preoperative localization study is necessary to practice
      UNE for primary hyperparathyroidism. Parathyroid US, done by an interested
      radiologist, with a 90 per cent accuracy rate, meets all these criteria.

PMID- 9655285
TI  - Clinical pathways for general surgeons: elective colectomy for recurrent acute
      diverticulitis.

PMID- 9655286
TI  - Progress in endocrine therapy for breast carcinoma.

PMID- 9655287
TI  - p53 sequence analysis predicts treatment response and outcome of patients with
      esophageal carcinoma.
AB  - BACKGROUND: The ability to predict biologic behavior and treatment responsiveness
      would be a valuable asset in the multimodality approach to esophageal carcinoma.
      The authors examined whether alterations of the p53 gene correlate with
      clinicopathologic parameters, response to preoperative chemotherapy/radiotherapy,
      and outcome in patients with esophageal carcinoma. METHODS.
      Histopathologic/genetic analysis of p53 was performed on formalin fixed, paraffin
      embedded tissues. Tissue sections were stained immunohistochemically for p53
      protein followed by topographic genotyping comprised of polymerase chain reaction
      amplification and direct sequencing of p53 exons 5-8. All patients received
      induction chemotherapy (5-fluorouracil, cisplatin, and alpha-interferon) and
      concurrent external beam radiotherapy (4500 centigrays) followed by resection.
      RESULTS: p53 analysis performed on 42 tumors from patients with potentially
      resectable esophageal carcinoma revealed 25 of the 42 tumors (59.5%) to be p53
      immunopositive; however, only 17 of the 42 tumors (40.5%) were proven to contain
      p53 point mutational damage in exons 8 (n=5), 5 (n=5), 7 (n=4), and 6 (n=3).
      Eight cases were weakly immunopositive and had no genotype mutation suggesting
      hyperexpression of normal wild-type p53. Genotyping also identified two
      immunonegative cases with deletion-type mutations (exons 5 and 6). Tissue samples
      collected before and after chemotherapy/radiotherapy exhibited fidelity in p53
      mutational genotype in all cases. The presence of a p53 point mutation positively
      correlated with pTNM stage (P=0.003) and residual disease in the resected
      specimen (P=0.01). Moreover, survival of patients with p53 mutations was
      significantly lower than that of patients without mutations (overall survival of
      21.6 months vs. 40 months; P=0.0038; and disease free survival of 14.1 months vs.
      38 months; P=0.0004). CONCLUSIONS: Histopathologic/genetic analysis is a better
      determinant of p53 mutational damage than immunohistochemistry alone and can be
      used as a prognostic marker for esophageal carcinoma. p53 genotyping may define a
      subset of patients who respond to chemotherapy/radiotherapy and may predict who
      potentially benefits from multimodality therapy.

PMID- 9655288
TI  - Changes in tumor marker levels as a predictor of chemotherapeutic effect in
      patients with gastric carcinoma.
AB  - BACKGROUND: Evaluating chemotherapeutic effect in patients with gastric carcinoma
      sometimes is difficult. The authors investigated whether changes in the serum
      levels of three tumor markers can be used to predict the clinical outcome after
      chemotherapy. METHODS: Thirty patients with advanced and recurrent gastric
      carcinoma were treated with continuous 5-fluorouracil and low dose cisplatin for
      4 weeks. Thirteen patients were treated neoadjuvantly prior to gastrectomy. The
      serum levels of carcinoembryonic antigen, carbohydrate antigen 19-9, and sialyl
      Tn antigen were measured prior to and after chemotherapy. Responders were defined
      as those in whom abnormal serum levels of all three markers decreased to at least
      50% of the pretreatment values and remained stable for at least 1 month. RESULTS:
      The tumor markers could be evaluated in 27 of 30 patients (90%). The median
      duration of survival for the 15 responders and 12 nonresponders was 17 months and
      6 months, respectively. There was a significant difference in the median duration
      of survival between the responders and nonresponders using the log rank test
      (P=0.0005). In the patients who received neoadjuvant therapy, the eight
      responders had a significantly longer survival period than did the three
      nonresponders (P=0.018). Seven of the eight responders showed evidence of tumor
      destruction histologically whereas none of the three nonresponders did.
      CONCLUSIONS: Changes in the serum levels of these tumor markers after
      chemotherapy may be an excellent prognostic indicator for patients with gastric
      carcinoma.

PMID- 9655289
TI  - Unique features of gastric carcinoma in the young: a population-based analysis.
AB  - BACKGROUND: It is suspected that young patients with adenocarcinoma have a more
      aggressive form of disease and therefore a poorer prognosis than older patients.
      METHODS: A retrospective cohort study used the population-based tumor registries
      of Orange, San Diego, and Imperial Counties. Cases (patients age < or =40 years
      with gastric carcinoma) were compared with controls (patients age >40 years with
      gastric carcinoma). RESULTS: The overall, age-adjusted incidence rate of gastric
      carcinoma was 10.2/100,000. Approximately 5.5% of 3,020 cases occurred in
      patients age <41 years. Young patients (especially whites and Latinos) were more
      likely to have distant metastases [45% versus 34%; odds ratio (OR)=2.6; 95%
      confidence interval (CI), 1.4-4.8; P < 0.001]. The histology of young patients
      (especially Latinos and Asians) was more likely to be signet ring cell (28%
      versus 15%; OR=2.3; 95% CI, 1.6-3.3; P < 0.001), and the grade of young patients
      (especially whites and Latinos) was more likely to be Grade 3 or 4 (according to
      the World Health Organization International Classification of Diseases for
      Oncology; 68% versus 56%; OR=2.1; 95% CI, 1.4-3.3; P < 0.001). The tumors of
      young patients (especially Asians) were less likely to be of the gastroesophageal
      junction (16% versus 27%; OR=0.47; 95% CI, 0.31-0.72; P < 0.001) and of the
      antrum (17% versus 22%; OR=0.62; 95% CI, 0.41-0.95; P=0.03) than the gastric
      body. Younger patients were more likely to receive chemotherapy (50% versus 28%;
      OR=2.7; 95% CI, 1.9-3.7; P < 0.001). Only patients age >70 years had an
      independent increased risk of dying from all causes in comparison with young
      patients (relative risk 1.46; P=0.01). CONCLUSIONS: Young gastric carcinoma
      patients have adverse clinical and pathologic features in comparison with older
      patients. In this study, young age was not found to be an independent predictor
      of overall survival.

PMID- 9655290
TI  - GLUT1 glucose transporter expression in colorectal carcinoma: a marker for poor
      prognosis.
AB  - BACKGROUND: Malignant cells exhibit increased glycolytic metabolism, and in many
      cases increased glucose transporter gene expression. The authors hypothesized
      that GLUT1 glucose transporter expression is increased in colorectal carcinoma,
      and that the degree of expression might have prognostic significance. METHODS:
      GLUT1 glucose transporter immunostaining was studied in normal colon and benign
      colon adenomas and in 112 colorectal carcinomas from patients for whom long term
      clinical outcome was known. RESULTS: GLUT1 immunostaining was absent in normal
      colorectal epithelium and tubular adenomas, and absent or only weakly apparent in
      tubulovillous adenomas. The majority of carcinomas (101 of 112; 90%) had GLUT1
      immunostaining. Tumors from 92 patients had low GLUT1 expression (< 50% of cells
      were GLUT1 positive) and 19 of these patients (21%) died of disease during follow
      up. In contrast, tumors from 20 patients had high GLUT1 expression (> 50% of
      cells were GLUT1 positive) and 9 of these patients (45%) died of disease during
      follow-up. Disease specific mortality was greater in patients with high GLUT1
      tumors (relative risk of 2.4; P=0.02). In a multivariate analysis to assess
      whether high GLUT1 staining correlated with increased mortality independently of
      Dukes stage, the risk of death from colon carcinoma in the group with high GLUT1
      staining was 2.3 times that in the group with low GLUT1 staining, a difference
      that approached statistical significance (P=0.07). CONCLUSIONS: GLUT1 glucose
      transporter expression is associated strongly with neoplastic progression in the
      colon, and assessment of the extent of GLUT1 immunostaining in colorectal
      carcinoma identifies patients with a poorer prognosis.

PMID- 9655291
TI  - Increased levels of phosphatidylinositol 3-kinase activity in colorectal tumors.
AB  - BACKGROUND: Phosphatidylinositol 3-kinase (PI 3-kinase), an enzyme that
      phosphorylates inositol phospholipids at the D-3 position of the inositol ring,
      has been implicated in the signaling pathways regulating cell growth by virtue of
      its activation in response to various mitogenic stimuli. In spite of the
      considerable attention PI 3-kinase has received with regard to its possible role
      in the mitogenic pathways in hematopoietic malignancies, there are few reports of
      investigations into PI 3-kinase activity in solid tumors. METHODS: Colorectal
      tumor tissue and normal-appearing colonic mucosa from the same patients were
      homogenized and solubilized and adjusted to equal protein levels. PI 3-kinase
      then was immunoprecipitated from 200 microg of the solubilized tissue using a
      polyclonal antibody to the p85 subunit of PI 3-kinase. PI 3-kinase activity was
      assessed using phosphatidylinositol as the substrate and the assay product
      analyzed by thin-layer chromatography. Phosphorylation of phosphatidylinositol in
      the D-3 position was confirmed by high performance liquid chromatography analysis
      of deacylated and deglycerated products. RESULTS: Thirty-two of the 37 tumors
      tested (86%) demonstrated increased PI 3-kinase activity compared with normal
      appearing mucosa from the same patients (overall mean increase+/-standard error
      of the mean=3.8+/-0.6-fold; P < 0.05, Student's t test for paired data). The
      frequency and extent of increased PI 3-kinase enzyme activity in tumors did not
      correlate with clinical parameters or the presence of oncogenic ras mutations.
      CONCLUSIONS: In this study colorectal tumors exhibited enhanced PI 3-kinase
      activity compared with normal colonic mucosa, raising the possibility that PI 3
      kinase may be a potential target for new strategies for the treatment of
      colorectal carcinoma.

PMID- 9655292
TI  - Long term results of single session percutaneous ethanol injection in patients
      with large hepatocellular carcinoma.
AB  - BACKGROUND: The objective of this study was to evaluate the indications for
      percutaneous ethanol injection (PEI) performed in a single session under general
      anesthesia for treating patients with cirrhosis and large (tumors > 5 cm)
      hepatocellular carcinoma (HCC), and relevant survival curves. METHODS: Between
      November 1991 and November 1996, 108 patients were treated (a total of 128
      procedures). They fell into 3 groups: 24 patients with single, encapsulated HCC
      measuring from 5-8.5 cm (Group A); 63 patients with single, infiltrating HCC
      measuring from 5-10 cm or multiple HCC (Group B); and 21 patients with advanced
      disease, either hepatic (Child's Class C) or neoplastic (symptomatic HCC or with
      portal thrombosis) type (Group C). The mean amount of ethanol injected was 62 mL.
      The average hospital stay was 3.8 days. The mean follow-up time was 40 months.
      RESULTS: The 1-, 2-, 3-, and 4-year survival rates were: 72%, 65%, 57%, and 44%,
      respectively, for Group A; 73%, 60%, 42%, and 18%, respectively, for Group B; and
      46%, 25%, and 0%, respectively, for Group C. Mortality was 0.7% (bleeding from
      esophageal varices in a Child's Class C patient). The rate of major complications
      was 4.6% (1 case of peritoneal hemorrhage, 1 case of severe liver failure, 1 case
      of transient renal insufficiency, 1 case of peritoneal seeding, and 2 cases of
      infarctions of a segment adjacent to the tumor). CONCLUSIONS: Single session PEI
      has been proven to be a valid alternative in patients otherwise treated
      surgically or with transcatheter arterial chemoembolization who present with
      adverse prognostic factors or risks for these therapies, and may be an option for
      selected patients with advanced disease previously excluded from any therapy.
      Risk conditions are marked portal or pulmonary hypertension or esophageal varices
      at risk of bleeding, superficial tumors with severe coagulation disorders,
      hyperfibrinolysis, chronic renal insufficiency, and obstructive jaundice.

PMID- 9655293
TI  - Natural killer cell activity in patients with hepatocellular carcinoma: a new
      prognostic indicator after hepatectomy.
AB  - BACKGROUND: Natural cytotoxicity mediated by natural killer (NK) cells is
      believed to play an important role in host anticancer defense mechanisms. The aim
      of this study was to examine the prognostic significance of NK cell activity
      after hepatectomy in patients with hepatocellular carcinoma. METHODS: The NK cell
      activity in 210 patients with hepatocellular carcinoma was measured and evaluated
      in relation to clinicopathologic variables using univariate and multivariate
      analyses. RESULTS: The NK cell activity was decreased significantly in
      hepatocellular carcinoma patients compared with the control groups (P < 0.001).
      No correlation was observed between NK cell activity and the clinicopathologic
      variables. Multivariate analyses indicated that NK cell activity as well as
      intrahepatic metastases, platelet count, and serum albumin level were independent
      prognostic factors. CONCLUSIONS: This study suggests that the preoperative NK
      cell activity will help predict recurrence and prognosis after hepatectomy in
      patients with hepatocellular carcinoma.

PMID- 9655295
TI  - Quality of life and psychosocial adjustment of young patients after treatment of
      bone cancer.
AB  - BACKGROUND: The aim of this study was to collect information about the
      psychosocial situation of young patients after multimodality therapy for bone
      cancer. METHODS: Selection criteria for patients were ages 15-30 years, tumor
      localization at the extremities, and an interval of at least 1 year since the end
      of treatment. Of 110 patients, 60 were willing to participate. Evaluation of
      psychosocial quality of life included assessment of psychosocial adjustment and
      age-appropriate achievements as well as identification of problems typical for
      this patient group. RESULTS: Approximately 80% of patients revealed, at the very
      most, only minor psychosocial problems. They were able to adapt well to their new
      living conditions, although strong efforts were necessary for them to deal with
      problems such as restricted mobility, catching up with school, or changing jobs
      or job orientation. Differences between patients and control subjects emerged in
      the areas of marital status, independent living, and parenthood. The most
      recently determined levels of education and income were similar. Neither clinical
      data nor physical or functional sequelae affected psychosocial adjustment, with
      one exception: patients diagnosed in adolescence had significantly more problems,
      especially in the area of social well-being, than patients diagnosed in childhood
      or early adulthood. CONCLUSIONS: Given the limitations of this study, the
      findings suggest that survivors of bone cancer are not necessarily at risk of
      developing long term emotional or social problems and are not precluded from
      leading active and independent lives.

PMID- 9655294
TI  - Technetium-99m methoxyisobutylisonitrile chest imaging of small cell lung
      carcinoma: relation to patient prognosis and chemotherapy response--a preliminary
      report.
AB  - BACKGROUND: The purpose of this preliminary study was to evaluate retrospectively
      the relation between chemotherapy response and survival time, using technetium
      99m methoxyisobutylisonitrile (Tc-99m MIBI) uptake in small cell lung carcinoma
      (SCLC) to detect the expression of multidrug resistance (mdr)-mediated 170-kDa P
      glycoprotein (PgP). METHODS: Before the administration of chemotherapy (which
      consisted of cisplatin 25 mg and etoposide 125 mg every day per 3-day course), 15
      male patients (ages 54-64 years) with SCLC were enrolled in this study to undergo
      Tc-99m MIBI chest imaging, including single photon emission computed tomography
      (SPECT) and planar imaging, for qualitative and quantitative assessments of PgP
      in their SCLC. RESULTS: In 12 of 15 cases (80%), SCLC could be detected by visual
      interpretation of the Tc-99m MIBI chest SPECT images. In 13 of 15 cases (87%), Tc
      99m MIBI chest SPECT images (either positive SPECT with good response or negative
      SPECT with poor response) correctly predicted chemotherapy response. The
      correlation between tumor uptake ratios obtained by planar images (total counts
      in the region of interest [ROI] of the tumor divided by total counts in the same
      size ROI of the contralateral normal lung) and survival days (from the time of
      SCLC diagnosis to the time of the patient's death) was both positive and good
      (correlation coefficient=0.83). CONCLUSIONS: Tc-99m MIBI chest images have the
      potential to demonstrate mdr-PgP expression in SCLC and to predict patient
      prognosis and chemotherapy response.

PMID- 9655296
TI  - Survival of premenopausal women with breast carcinoma: effects of menstrual
      timing of surgery.
AB  - BACKGROUND: It is controversial whether the timing of tumor excision relative to
      the menstrual cycle influences the survival of patients with breast carcinoma.
      METHODS: Premenopausal patients (n=614) who had surgery for invasive,
      nonmetastatic breast carcinoma during the period 1978-1988 participated in an
      epidemiologic survey, reporting their menstrual cycle length and the date of
      their last menses. We ascertained deaths from any cause before 1993. RESULTS:
      Using Cox modeling, we found a nonlinear variation in the relative risk (RR) of
      death according to the timing of surgery during the menstrual cycle. The curve
      was best described by a cosine transformation of a 28-day cycle. For patients who
      had breast carcinoma surgery on the estimated day of ovulation, the risk of death
      was 0.59 (95% confidence limits [CLI=0.39-0.89, P=0.013) compared with patients
      who had surgery at the approximate time of menses. We observed this for patients
      treated in 1978-1981 (RR=0.43, 95% CL=0.23-0.83, P=0.011) and 1982-1983 (0.25,
      95% CL=0.10-0.63, P=0.003), but not in 1984-1988 (1.48, 95% CL=0.64-3.4). The
      difference observed for 1984-1988 was explained by a significant improvement in
      the mortality rate (P=0.0004) for women whose surgery took place during menses or
      near to the date predicted for the next menses. No such improvement for women who
      underwent breast carcinoma surgery around the time of ovulation was observed
      during the period 1984-1988. These changes were not explained by the performance
      of lumpectomy or the increasing interval between biopsy and tumor excision.
      CONCLUSIONS: The shape of the survival curve contradicted the idea that it could
      be explained by levels of circulating estradiol or progesterone. Because
      observations that surgery was affected by menstrual timing seem not to have
      persisted beyond the mid-1980s, this study should not be used to support
      recommendations that surgeons perform breast carcinoma surgery on any particular
      day of the menstrual cycle.

PMID- 9655297
TI  - Modulation of biomarkers in minimal breast carcinoma: a model for human breast
      carcinoma progression.
AB  - BACKGROUND: The widespread use of diagnostic breast imaging has yielded an
      increase in the detection of in situ, microinvasive, and small invasive
      carcinomas and has provided opportunities to study the earliest stages of breast
      carcinoma development. The authors of this report analyzed the pathobiologic
      features of 577 minimal breast carcinomas (MBCs), including in situ carcinomas
      and invasive carcinomas < or =1 cm, according to the definition given by Hartmann
      in Cancer (1984;53:681-4). METHODS: Estrogen and progesterone receptors (ER and
      PR), proliferation index (PI), and p53 and neu expression were studied by
      immunohistochemical technique and measured by quantitative image analysis in 99
      pure in situ carcinomas (ISCp); in 105 mixed invasive/in situ carcinomas, with a
      separate analysis of in situ (ISCm) and invasive (ICm) components; and in 373
      invasive carcinomas < or =1 cm (IC). Follow-up data were available for 164
      invasive carcinomas. RESULTS: A progressive increase in the levels of hormone
      steroid receptors, from the lowest in ISCm to the highest in IC, was observed
      (ER, P< 0.001; PR, P=0.005). Levels of PI and p53 expression were higher in ISCm
      than in the other categories (PI, P=0.007; p53, P=0.046). Overexpression of neu
      was greater in ICm than in IC (P=0.013). Younger women (< or =40 years) with
      invasive carcinoma had worse biologic profiles, with lower ER (P < 0.001) and
      higher PI (P=0.021), neu (P=0.008), and p53 (P=0.040). It was demonstrated
      clinically that PI and neu were the biologic markers with the highest predictive
      prognostic values in univariate analysis (PI for recurrence, P < 0.015; neu for
      recurrence and overall survival, P < 0.001 and P < 0.007, respectively) and in
      multivariate analysis (neu for recurrence and overall survival, P < 0.007 and P <
      0.017, respectively). CONCLUSIONS: Biologic phenotypes of MBC can be interpreted
      as reflecting a dimension of neoplastic progression capacity that is independent
      of tumor size. This study suggests that biologic markers can be integrated with
      traditional pathologic indicators for accurate staging of patients.

PMID- 9655298
TI  - Body mass predicts the survival of patients with new International Federation of
      Gynecology and Obstetrics Stage IB1 and IB2 cervical carcinoma treated with
      radical hysterectomy.
AB  - BACKGROUND: The authors evaluated the impact of body mass on survival and
      morbidity of patients with new International Federation of Gynecology and
      Obstetrics (FIGO) Stage IB1 and IB2 cervical carcinoma managed with radical
      hysterectomy. METHODS: Two hundred twenty-nine patients with Stage IB1 or IB2
      cervical carcinoma treated with radical hysterectomy were studied in a
      multivariate logistic regression analysis. The body mass index (BMI) and the
      ponderal index (PI) were used as measures of body mass and were analyzed as
      predictors of recurrence, survival, and complications in light of the new staging
      system. RESULTS: Twenty-seven of 229 patients died of recurrent disease. A low
      BMI or a high PI were predictive of poor survival. Tumor greatest dimension,
      lymph node involvement, BMI, and PI were all independent predictors of survival
      (P=0.0006). The only independent predictor of complications was para-aortic lymph
      node dissection (P=0.0026). CONCLUSIONS: Cervical carcinoma patients with a low
      body mass, as indicated by a low BMI or a high PI, were found to have poor
      survival after undergoing radical hysterectomy. Additional predictors of poor
      survival included lymph node metastases and increased tumor size. BMI and PI are
      more important predictors of survival than the new FIGO Stages IB1 and IB2. Body
      mass is not predictive of complications.

PMID- 9655299
TI  - Bax protein expression correlates with radiation-induced apoptosis in radiation
      therapy for cervical carcinoma.
AB  - BACKGROUND: Bax protein serves as a positive regulator of apoptosis by forming
      heterodimers with bcl-2 protein, thereby promoting cell survival. It is unclear
      whether the regulation of apoptosis reported in many studies is applicable to the
      apoptotic phenomenon observed in conventional fractionated radiation therapy for
      cervical carcinoma. METHODS: The authors assessed the relation between apoptosis
      and the expression of Bax and bcl-2 protein in fractionated radiation therapy for
      cervical carcinoma by using in situ nick end labeling (ISEL) and
      immunohistochemical methods. RESULTS: Specimens were excised from the cervical
      tumors of 20 patients before and after administration of a total irradiation dose
      of 9 gray (Gy). The apoptotic cell index (AI) in tumor cells was 0.22% before
      irradiation and 1.20% after the administration of the 9 Gy, which represented a
      significant increase (P=0.0004). The positive rate of Bax protein increased from
      15% (in 3 of 20 patients) before irradiation to 60% (in 12 of 20 patients) after
      the 9 Gy was administered, a statistically significant change (P=0.0126). In
      addition, there was a significant correlation between Bax protein expression and
      apoptosis positivity after the 9 Gy was administered (P=0.018). CONCLUSIONS:
      These results suggest that Bax protein is associated with apoptosis induced by
      fractionated radiation therapy.

PMID- 9655300
TI  - Progesterone therapy for endometrial carcinoma reduces cell proliferation but
      does not alter apoptosis.
AB  - BACKGROUND: Although the anticancer effects of progesterone therapy for patients
      with endometrial carcinoma are widely acknowledged, a detailed assessment of the
      resultant morphologic alterations in tumor tissue kinetics has hitherto been
      lacking. METHODS: Biopsy and hysterectomy specimens of 14 endometrial carcinomas
      (endometrioid-type) before and during progesterone therapy were studied to
      clarify changes in apoptosis and cell proliferation and their relation to
      morphologic alterations. The extent of squamous differentiation within tumor
      lesions was also examined. RESULTS: In the good-response group, tumor cells took
      on characteristics of normal endometrial gland cells in the secretory phase. A
      positive correlation between reduction in the mitotic index and the degree of
      morphologic alterations during hormone therapy was observed, but the frequency of
      apoptotic cells did not vary. In both the good-response and poor-response groups,
      development or enlargement of squamous areas was observed, in comparison with the
      initial biopsy specimens. CONCLUSIONS: These results suggest that prolonged
      progesterone administration can suppress cell proliferation in endometrial
      carcinomas through tumor cell differentiation without altering apoptosis,
      resulting in a shift in tissue kinetics toward a relative predominance of cell
      deletion. In addition, increases in the occurrence of squamous areas within
      tumors do not always appear to be related to treatment efficacy.

PMID- 9655301
TI  - A c-rasHa mutation in the metastasis of a human papillomavirus (HPV)-18 positive
      penile squamous cell carcinoma suggests a cooperative effect between HPV-18 and c
      rasHa activation in malignant progression.
AB  - BACKGROUND: Human papillomaviruses (HPV) have been implicated in the etiology of
      anogenital squamous epithelial tumors. Of the 65 HPV strains, subtypes HPV-16 and
      HPV-18 frequently are associated with malignant conditions and are capable of
      transforming keratinocytes in vitro. However, additional cellular changes are
      necessary to confer tumorigenicity to HPV-infected cells. Secondary events
      implicated in the progression to malignancy include loss of tumor suppressor
      genes such as p53 and/or activation of cellular oncogenes such as c-rasHa.
      METHODS: Polymerase chain reaction (PCR) was used to identify HPV-16 or HPV-18
      genetic sequence in primary penile squamous cell carcinoma and two inguinal lymph
      node metastases. p53 and c-rasHa loci were analyzed by sequencing of PCR
      amplified genomic DNA. RESULTS: HPV-18 but not HPV-16 infection was found in the
      primary carcinoma and in inguinal metastases occurring 5 and 7 years after the
      initial lesion. Sequence analysis did not identify any p53 mutations in the
      primary carcinoma or its metastases. However, although the primary lesion and the
      5-year metastasis encoded wild-type c-rasHa, the 7-year metastasis had a missense
      mutation within c-rasHa codon 61. CONCLUSIONS: To the authors' knowledge, this is
      the first report of an activating c-rasHa mutation associated with squamous cell
      carcinoma of the penis. The presence of activated c-rasHa in the second
      metastasis but not in the first metastasis or the primary lesion suggests that
      activation of c-rasHa may be a late event in the malignant progression of HPV-18
      associated penile squamous cell carcinoma. Analysis of additional samples from
      primary lesions and their resultant metastases is necessary to elucidate the
      incidence and significance of c-rasHa activation in penile squamous cell
      carcinoma.

PMID- 9655302
TI  - Modeling postradiation prostate specific antigen level kinetics: predictors of
      rising postnadir slope suggest cure in men who remain biochemically free of
      prostate carcinoma.
AB  - BACKGROUND: The goals of this study are twofold: 1) to describe the postradiation
      kinetics of nonrecurring prostate carcinoma based on prostate specific antigen
      (PSA) levels in men who remain biochemically free of disease; and 2) to determine
      predictors of all three components of the resulting piecewise exponential model
      based on pretreatment and treatment characteristics. METHODS: Between March 1988
      and May 1994, 153 patients with T1-T3 nonmetastatic prostate carcinoma were
      treated definitively with radiation therapy and at last follow-up had not failed
      biochemically (PSA rising on 2 consecutive occasions to a level > 1.0 ng/mL or 3
      consecutive elevations). All patients were required to have at least 6
      posttreatment PSA determinations and a minimum follow-up of 36 months. The median
      follow-up was 53 months (range, 36-94 months). A piecewise exponential model was
      used to describe the mean PSA levels because 1) the kinetics of postradiation PSA
      levels appear to follow first-order rate processes, and 2) there is evidence that
      PSA levels may rise slightly several years after treatment. Nonlinear mixed
      effects modeling was used in this situation because of the aforementioned
      nonlinearity and because variability between patients and within patients (PSA
      variation) must be taken into account. In addition, this methodology allows for
      modeling parameters as a function of patient and treatment characteristics.
      RESULTS: The random effects model based on the entire patient population
      demonstrated that PSA levels do not continue to drop 3 years after treatment, and
      that in fact the levels begin to rise slowly between 2-3 years after treatment.
      Pretreatment PSA was the only independent predictor of baseline PSA at time zero
      (end of radiation therapy). Gleason score was the only independent predictor of
      the rate of PSA decline after treatment, in which tumors with Gleason scores 7-10
      drop at a slower rate than do tumors with Gleason scores 2-6. Finally,
      pretreatment prostate volume was the only independent predictor of the postnadir
      rise in PSA level, in which larger volumes translate to a steeper slope.
      CONCLUSIONS: The fact that pretreatment PSA level is the only independent
      predictor of the baseline PSA at time zero is not surprising. The observation
      that patients with tumors with higher Gleason scores have a slower rate of
      decline is in agreement with previous reports that these tumors contribute less
      PSA per unit volume than do tumors with moderate to well differentiation.
      Finally, the fact that no tumor-related characteristic (only pretreatment
      prostate volume) was predictive independently of the observed postnadir rise in
      PSA level suggests that these patients were cured.

PMID- 9655303
TI  - Correlation of color Doppler flow in the prostate with tissue microvascularity.
AB  - BACKGROUND: The pathophysiology of increased color Doppler (CD) flow has not
      previously been addressed in histologic evaluations of microvascular parameters.
      In this study, the authors attempted to define the differences between benign and
      malignant biopsy cores found in regions of the prostate with normal and high CD
      flow. METHODS: Forty patients were retrospectively chosen for CD histologic
      comparison, each of whom had a core from a sextant biopsy with the following
      characteristics: malignant tissue with distinct increased CD flow (n=11),
      malignant tissue with normal CD flow (n=10), benign tissue with distinctly
      increased CD flow (n=9), or benign tissue with normal CD flow (n=10). All biopsy
      cores were stained with factor VIII-related antigen to identify microvasculature
      and to determine the number of microvessels per square millimeter (mm2) in an
      average cross-sectional area of microvessels, the percentage of tissue occupied
      by microvasculature, and the Gleason score. RESULTS: In biopsies of benign
      tissue, high CD flow was associated with greater numbers (P < 0.025) of vessels
      of similar size than in normal flow benign biopsies. Biopsies of malignant tissue
      contained significantly greater numbers (P < 0.01) of much smaller vessels (P <
      0.0005) than biopsies of benign tissue. In biopsies of malignant tissue, no
      significant differences in microvasculature parameters were noted between high
      and normal CD flow, yet biopsies with high CD flow had average Gleason score of
      6.7 compared with only 5.9 for biopsies with normal CD flow (P < 0.025).
      CONCLUSIONS: Increased CD flow in biopsies of benign tissue was correlated with a
      greater number of vessels/mm2, yet all biopsies of malignant tissue had more
      vessels/mm2 than those of benign tissue. Increased CD flow in biopsies of
      malignant tissue cannot be explained by standard microvasculature analysis but
      significantly guides biopsies to regions with a greater Gleason score.

PMID- 9655304
TI  - Radical cystectomy for elderly patients with bladder carcinoma: an updated
      experience with 404 patients.
AB  - BACKGROUND: The authors evaluated the experiences at their institution with
      radical cystectomy and urinary diversion performed on elderly bladder carcinoma
      patients to determine whether age had an impact on the clinical or functional
      results for this group of patients. METHODS: Between August 1971 and December
      1996, 404 patients age 70 years or older (median age, 74 years) underwent radical
      cystectomy and urinary diversion for invasive bladder carcinoma: 352 (87%) were
      ages 70-79 years and 52 (13%) were age 80 years or older. Data analyzed included
      the following: perioperative mortality; early (within 90 days after surgery) and
      late (more than 90 days after surgery) postoperative complications, related and
      unrelated to the urinary diversion; length of hospital stay; pathologic staging;
      and clinical outcome. These data were then compared with those for 762 patients
      younger than 70 years (median age, 61 years) who underwent the same procedure
      during the same time period. RESULTS: The overall mortality rate for patients age
      70 years or older was 2.8% (3.2% for those ages 70-79 years, 0% for those age 80
      years or older), compared with 2% for patients younger than 70 years. The early
      complication rate for patients age 70 years or older was 32%, compared with 25%
      for patients younger than 70 years. Patients age 80 years or older had a similar
      early complication rate of 29%. Late postoperative complications occurred in
      12.4% of patients age 70 years or older, compared with 22.8% of patients younger
      than 70 years. There was no significant difference between the two groups with
      regard to pathologic stage or length of hospital stay. The 3-year and 5-year
      overall survival rates for patients age 70 years or older were 60% and 53%,
      respectively, compared with 68% and 63%, respectively, for patients younger than
      70 years (P=0.001). There was no statistical difference between the groups when
      rates of disease recurrence were compared (P=0.3627). The 5-year recurrence rate
      for patients age 70 years or older was 35%, compared with a 5-year recurrence
      rate of 31% for patients younger than 70 years. CONCLUSIONS: These data suggest
      that an aggressive, curative, radical surgical approach and urinary diversion may
      be a viable treatment strategy for properly selected elderly patients who are in
      generally good health and require definitive therapy for invasive bladder
      carcinoma.

PMID- 9655305
TI  - Treatment of cutaneous and subcutaneous tumors with electrochemotherapy using
      intralesional bleomycin.
AB  - BACKGROUND: Electrochemotherapy (ECT) is performed by locally administering a
      chemotherapeutic agent in combination with electric pulses. Previous clinical
      studies have demonstrated the effectiveness of ECT. In these initial trials, the
      drug was administered intravenously, followed by administration of electric
      pulses directly to the tumor. This study was initiated to determine whether an
      intralesional injection of the drug in combination with electric pulses could
      provide an improved result. A group of 34 patients was studied. METHODS: The dose
      of intralesional bleomycin was based on tumor volume. This was followed 10
      minutes later by 6 or 8 99-microsec pulses of electricity at an amplitude of 1.3
      kV/cm. Both the bleomycin and the electric pulses were administered after 1%
      lidocaine with epinephrine solution was injected around the treatment site.
      RESULTS: All patients responded to the treatment. Responses were observed in 142
      (99%) of 143 metastatic nodules or primary tumors within 12 weeks, with complete
      responses observed in 130 (91%) of the nodules. No complete responses were
      observed in nodules treated with bleomycin only or electric pulses only. Random
      biopsies confirmed the clinical findings. All patients tolerated the procedure
      well, and no significant side effects were noted. Muscle contraction was evident
      during administration of each electric pulse but promptly subsided after the
      pulse. CONCLUSIONS: ECT was shown to be an effective local treatment for
      cutaneous malignancies. The results suggest that ECT may have a tissue-sparing
      effect and result in minimal scarring. ECT may be a suitable alternative therapy
      for the treatment of basal cell carcinoma, local or regional recurrent melanoma,
      and other skin cancers.

PMID- 9655306
TI  - Cell turnover parameters in small and large cell varieties of primary intestinal
      non-Hodgkin's lymphoma.
AB  - BACKGROUND: In contrast to primary gastric lymphoma, primary intestinal lymphoma
      is an uncommon condition with a poorer outcome, perhaps due to differences in its
      pathogenesis. In this study, the authors analyzed the roles of proliferation and
      apoptosis in the pathogenesis of intestinal lymphoma. METHODS: Fifty-one cases of
      intestinal non-Hodgkin's lymphoma (NHL) (10 small B-cell mucosa-associated
      lymphoid tissue [MALT] NHLs, 12 large B-cell MALT NHLs, 18 large B-cell NHLs, 2
      small T-cell NHLs, 7 large T-cell NHLs, and 2 mantle cell NHLs) were studied for
      the immunohistochemical expression of MIB-1 and the TUNEL assay as well as the
      expression of bcl-2 and p53, both of which are regulatory gene products involved
      in apoptosis. RESULTS: The median proliferation index (PI) was 37.3%, and the
      median apoptotic index (AI) was 1.10%. The respective values of PI and AI were
      5.8% and 0.06% in small B-cell MALT lymphoma, 52.8% and 0.24% in large B-cell
      MALT lymphoma, 58.85% and 1.36% in large B-cell lymphoma, 30.9% and 1.93% in
      mantle cell lymphoma, 18.13% and 1.25% in small T-cell lymphoma, and 43.4% and
      1.93% in large T-cell lymphoma. In an analysis of B-cell NHL only (with mantle
      cell NHL excluded), proliferative and apoptotic indices were positively
      correlated (correlation coefficient=0.563, P < 0.001). Furthermore, high bcl-2
      expression was inversely correlated with both PI and AI. Expression of p53 was
      observed in 8 cases (1 small cell lymphoma and 7 large cell lymphomas).
      CONCLUSIONS: Small cell lymphomas had low AI and PI values, whereas large cell
      lymphomas had high AI and PI values. Apoptosis and proliferation were positively
      correlated, and higher expression of bcl-2 was associated with lower rates of
      apoptosis.

PMID- 9655307
TI  - Treatment of diencephalic syndrome with chemotherapy: growth, tumor response, and
      long term control.
AB  - BACKGROUND: The diencephalic syndrome (DS), which is manifested by progressive
      emaciation and failure to thrive in an apparently alert, cheerful infant, usually
      is due to a low grade hypothalamic glioma. Treatment with aggressive surgery
      and/or radiotherapy is variably successful in controlling disease and may result
      in severe neurologic sequelae. Chemotherapy recently has been shown to be
      effective in patients with low grade gliomas of childhood, but it is used
      infrequently in those with DS. METHODS: The authors evaluated the efficacy of a
      regimen of carboplatin and vincristine on improving weight, causing tumor
      shrinkage, and delaying the need for alternative therapies in seven children
      (ages 9-20 months; median age, 11 months) with DS. Five patients weighed less
      than the 5th percentile for their age at the start of the study, one weighed
      within the 10th percentile, and one weighed within the 25th percentile. RESULTS:
      At follow-up (range, 6-54 months; median, 28 months), the patients' weights had
      increased by 66-95% (median, 80%). On magnetic resonance imaging, four patients
      had a >50% reduction in tumor mass, one had a 25-50% reduction, and two had
      stable disease. In those patients with radiographic response to treatment, weight
      gain was accomplished with oral feedings in four of five patients, whereas those
      with stable disease required nasogastric, nasojejunal, or gastrostomy tube
      supplementation to maintain weight. Disease progression occurred at a median of
      24 months after initiation of chemotherapy, and two patients remained free of
      progressive disease at last follow-up. Five patients were alive a median of 59
      months from diagnosis. The need for radiation or other therapies was delayed in
      six of seven children. Therapy was tolerated without significant toxicities.
      CONCLUSION: The authors conclude that treatment of DS with a carboplatin and
      vincristine regimen results in demonstrable weight gain, may result in tumor
      shrinkage, and in some cases, significantly delays the need for alternative
      therapies.

PMID- 9655308
TI  - Quality of life and survival: the role of multidimensional symptom assessment.
AB  - BACKGROUND: Recent data from clinical trials suggest that quality-of-life (QOL)
      measurements may independently predict survival. The relation between survival
      and QOL measurements was tested among 122 inpatients and 96 outpatients with
      malignancies at one of four sites (colon, breast, ovary, or prostate) who
      participated in a cross-sectional validation study of the Memorial Symptom
      Assessment Scale (MSAS), a measure of the frequency of, severity of, and distress
      caused by physical symptoms. METHODS: The relation between MSAS summary scores
      and survival was evaluated in a multivariate analysis that adjusted concurrently
      for other important covariates, such as age, site and extent of disease,
      inpatient status, Karnofsky performance status (KPS), and other QOL measurements.
      RESULTS: In the multivariate analysis, extent of disease (P < 0.0001), inpatient
      status (P=0.014), higher MSAS physical symptom subscale score (P=0.004), and
      lower KPS score (P=0.009) independently predicted decreased survival. Other QOL
      measurements did not contribute significantly to the model. CONCLUSIONS: The MSAS
      physical symptom subscale score significantly predicts survival and adds to the
      prognostic information provided by KPS and extent of disease. Patients may be
      under-assessed regarding both the number and the severity of symptoms.
      Measurements of physical symptoms and related distress offer additional
      prognostic information concerning the survival of patients with cancer and may
      account for the predictive value of QOL scores.

PMID- 9655309
TI  - Undiagnosed malignancy in patients with deep vein thrombosis: incidence, risk
      indicators, and diagnosis.
AB  - BACKGROUND: The reported incidence of a subsequent diagnosis of malignancy in
      patients presenting with deep vein thrombosis (DVT) varies from 2-25%. Risk
      indicators and diagnostic procedures to be performed in these patients are
      controversial. METHODS: Four hundred consecutive patients with confirmed DVT
      included in a randomized clinical trial were followed prospectively for 6 months.
      The incidence of a subsequent diagnosis of malignancy was calculated and compared
      between patients with unexplained DVT and patients with secondary DVT. Potential
      risk indicators for subsequent malignant disease were evaluated. RESULTS: Of the
      400 patients, 70 already had been diagnosed with malignancy; another four
      patients were lost to follow-up. Of the remaining 326 patients, 10 new
      malignancies were diagnosed among 137 patients with unexplained DVT (7.3%) and 3
      new malignancies were diagnosed in 189 patients with secondary DVT (1.6%). The
      relative risk was 4.6 (95% confidence interval, 1.3-16; P=0.009). Age, gender, or
      location of the DVT had no significant effect on the incidence of diagnosis when
      adjusted for unexplained DVT. Ten of these 13 patients (77%) had abnormal
      clinical findings suggestive of malignancy at the time of presentation with DVT.
      CONCLUSIONS: Unexplained DVT is a significant risk indicator of underlying
      malignancy. The majority of patients with undiagnosed malignancy have some
      clinical abnormality suggestive of underlying malignancy at the time of
      presentation with unexplained DVT. A simple clinical evaluation comprised of
      medical history, physical examination, routine laboratory tests, and chest X-ray
      can detect such patients. Extensive screening of all patients presenting with
      unexplained DVT does not appear to be justified.

PMID- 9655310
TI  - The Gothenburg breast screening trial: first results on mortality, incidence, and
      mode of detection for women ages 39-49 years at randomization.

PMID- 9655311
TI  - Acute infectious purpura fulminans: pathogenesis and medical management.
AB  - Purpura fulminans (PF) is a potentially disabling and life-threatening disorder
      characterized by acute onset of progressive cutaneous hemorrhage and necrosis,
      and disseminated intravascular necrosis. Acute infectious PF occurs most commonly
      in the setting of meningococcemia due to elaboration of endotoxin. Presence of
      purpura, particularly when generalized, is an important predictor of a poor
      outcome following meningococcal infection. Histopathologic hallmarks of acute
      infectious PF are dermal vascular thrombosis and secondary hemorrhagic necrosis,
      findings which are identical to those of the Shwartzman reaction. Acute
      infectious PF and the Shwartzman reaction have a common pathogenesis, involving a
      disturbance in the balance of anticoagulant and procoagulant activities of
      endothelial cells. This disturbance, which is triggered by endotoxin, appears to
      be mediated by cytokines, particularly interleukin-12, interferon-gamma, tumor
      necrosis factor-alpha, and interleukin-1, leading to the consumption of proteins
      C and S and antithrombin III. State-of-the-art therapeutic interventions based on
      recent advances in our understanding of the pathogenesis of acute infectious PF
      are discussed.

PMID- 9655312
TI  - Bullous pemphigoid and epidermolysis bullosa acquisita: presentation, prognosis,
      and immunopathology in 11 children.
AB  - The immunobullous diseases bullous pemphigoid (BP) and epidermolysis bullosa
      acquisita (EBA) are very rare in childhood. Although case studies have been
      detailed, there are no reports of a large series of patients documenting the
      effectiveness of treatment and long-term prognosis. We report the clinical
      presentation, immunopathologic features, disease course, and long-term prognosis
      of BP and EBA in a series of 11 children. The initial diagnoses based on clinical
      features were BP (5), EBA (3), and chronic bullous disease of childhood (CBDC)
      (3). These were subsequently revised from BP to EBA (2), CBDC to BP (2), and CBDC
      to BP or EBA (1) following the results of direct and indirect immunofluorescence
      and immunoblotting. Analysis of IgG subclasses in eight cases showed that the
      predominant subclasses were IgG1 (8) and IgG4 (6). The clinical features appeared
      to be highly variable, and in patients presenting with inflammatory blistering,
      laboratory studies were required in order to differentiate between BP and EBA.
      All patients improved on treatment with corticosteroids and/or sulfones, although
      treatment regimens showed wide variation. Their diseases tended to remit within 2
      years, and their long-term prognosis was good.

PMID- 9655313
TI  - Median raphe cysts of the penis: a report of five cases.
AB  - Cysts of the median raphe are embryologic developmental anomalies of the male
      genitalia. Although generally present since birth, these lesions tend to manifest
      in adult life. Histologically the cysts are characterized by a pseudostratified
      epithelium in the middle dermis. The early age at consultation is a common
      characteristic in four of the five patients reported herein and is probably due
      to the growing concern among the general population about skin problems.

PMID- 9655314
TI  - S. aureus isolation from the lesions, the hands, and the anterior nares of
      patients with atopic dermatitis.
AB  - Staphylococcus aureus colonization is common in atopic dermatitis (AD) and can
      exacerbate the disease. Additionally, some evidence shows that patients with AD
      may act as reservoirs for S. aureus transmission to others. This study compared
      S. aureus colonization in AD patients and their caregivers with control patients
      and their caregivers. Quantitative cultures were obtained from the lesions,
      clinically normal skin, hands, and anterior nares of 100 patients with AD, 100
      controls with other cutaneous disorders, and 200 caregivers. AD patients had a
      significantly greater carriage of S. aureus from lesional and clinically normal
      skin as well as the hand. Significant increases in carriage of S. aureus were
      found in the anterior nares and hands of caregivers of AD patients compared with
      control caregivers. Topical corticosteroid use did not affect recovery of S.
      aureus. There was a significant correlation between recovery of S. aureus from
      lesional skin and recovery from the anterior nares (p = .002) and hands (p <
      .0001). These findings suggest that the anterior nares and the hands may be
      important reservoirs and vectors for transmission of S. aureus to lesional skin
      and to close contacts of these patients.

PMID- 9655315
TI  - Resolution of xanthomas in Alagille syndrome after liver transplantation.
AB  - Alagille syndrome (arteriohepatic dysplasia) is a genetic disorder with autosomal
      dominant transmission which has been localized to chromosome 20p. Cutaneous
      manifestations include jaundice, pruritus, and widespread xanthomata. We report a
      child with severe Alagille syndrome in whom orthotopic liver transplantation
      caused rapid resolution of disfiguring xanthomas.

PMID- 9655316
TI  - Juvenile xanthogranuloma with hematologic changes in dizygotic twins: report of
      two newborn infants.
AB  - We describe the first reported instances of juvenile xanthogranuloma (JXG) in
      dizygotic twins. They had characteristic skin lesions and subcutaneous nodules as
      well as hepatomegaly, anemia, and thrombocytopenia. These extracutaneous symptoms
      improved in 5 months, coincident with the resolution of the skin lesions.
      Although most patients with JXG have only cutaneous symptoms, some show such
      dramatic extracutaneous manifestations that the possibility of malignant disease
      is occasionally the principle concern. It is therefore necessary to make a
      precise diagnosis based on specific immunohistochemical and ultrastructural
      findings, and to evaluate for other organ involvement, including hematologic
      abnormalities.

PMID- 9655317
TI  - Scleroatrophic syndrome of Huriez in an infant.
AB  - We present a 3-year-old boy with scleroatrophic syndrome of Huriez, a rare
      autosomal dominant condition with only seven affected families worldwide.
      Although assumed to occur from birth, an evolving case has not previously been
      documented. Infants do not possess the focal areas of keratoderma on the palms or
      soles; these develop in adult life. Of particular interest is the high incidence
      of squamous cell carcinomas that arise from the scleroatrophic skin.

PMID- 9655318
TI  - Congenital lipoblastomatosis of the lower extremity in a neonate.
AB  - Lipoblastomatosis is a benign tumor of embryonic fat that is more common in male
      infants. It occurs more frequently in the soft tissues of the extremities. The
      diagnosis is made by biopsy, which shows globules of lipocytes and lipoblasts
      mixed with spindled and myxoid cells. MRI demonstrates fat infiltrating fascia
      and muscle. The infant described had clinical, histologic, and radiologic
      findings consistent with this diagnosis. Because of concern that total excision
      would compromise function, a debulking procedure is planned.

PMID- 9655319
TI  - Congenital erosive and vesicular dermatosis healing with reticulated supple
      scarring: report of three new cases and review of the literature.
AB  - Congenital erosive and vesicular dermatosis healing with reticulated, supple
      scarring is a rare disease with seven reported cases in the literature. This
      congenital cutaneous defect of unknown etiology presents with patchy or
      generalized erosions and vesicles at birth that heal with striking reticulated
      scarring. We report three new cases of this rare disease and review the
      literature.

PMID- 9655320
TI  - Keratitis, ichthyosis, and deafness (KID) syndrome in half sibs.
AB  - The keratitis, ichthyosis, and deafness (KID) syndrome is a rare congenital
      disorder of the ectoderm characterized by diffuse hyperkeratotic erythroderma,
      keratitis with neovascularization of the cornea, and severe neurosensory hearing
      loss. A familial occurrence of this syndrome has been mentioned in four reports
      including three of vertical transmission and one of two affected sisters born
      from consanguineous, unaffected parents. We report for the first time a familial
      case of KID syndrome in two half siblings born to the same unaffected mother.
      This new observation allows us to propose various hypotheses about its mode of
      inheritance.

PMID- 9655321
TI  - Solitary giant molluscum contagiosum of the sole.
AB  - Molluscum contagiosum of the sole is extremely rare and only three cases have
      been reported in the literature. We report a solitary giant molluscum contagiosum
      on the left sole of a 5-year-old boy, which should be clinically differentiated
      from plantar wart, eccrine poroma, epidermal cyst, foreign body granuloma,
      cryptococcal infection, and pyogenic granuloma.

PMID- 9655322
TI  - Itraconazole pulse therapy for tinea capitis: a novel treatment schedule.
AB  - Itraconazole 5 mg/kg/day given as pulse therapy, each of 1 week duration, for 1
      to 3 pulses appears to be an effective and safe method of treating tinea capitis.
      The number of pulses of therapy may depend upon several factors, including the
      severity of disease and area of involvement. Controlled studies are needed to
      determine the number of pulses of itraconazole required to treat tinea capitis.

PMID- 9655323
TI  - Tinea capitis: fluconazole in Trichophyton tonsurans infection.
AB  - Tinea capitis is the most common dermatophyte infection in children. Trichophyton
      tonsurans is the most common etiologic agent in the United States, and for more
      than four decades the standard therapy has been griseofulvin. The availability of
      newer, and often more effective, antifungal drugs creates the opportunity for
      choice and the ability to optimally tailor treatment for a particular patient.
      Fluconazole is an azole antifungal drug available in a pleasant, well-tolerated,
      liquid formulation ideal for the pediatric population. It has a good safety
      profile and is approved in the United States for use in children, although not
      for tinea capitis. We present five patients with tinea capitis successfully
      treated with fluconazole.

PMID- 9655324
TI  - Pigmented palmar patch in a child.

PMID- 9655325
TI  - What syndrome is this? Waardenburg syndrome.

PMID- 9655326
TI  - Peripheral nerve blocks for warts: taking the cry out of cryotherapy and laser.

PMID- 9655327
TI  - Acropigmentation of Dohi in a 12-year-old boy.

PMID- 9655328
TI  - Colocalization of vitiligo and psoriasis in a 9-year-old boy.

PMID- 9655329
TI  - The crystal structure of Lactococcus lactis dihydroorotate dehydrogenase A
      complexed with the enzyme reaction product throws light on its enzymatic
      function.
AB  - Dihydroorotate dehydrogenases (DHODs) catalyze the oxidation of (S)
      dihydroorotate to orotate, the fourth step and only redox reaction in the de novo
      biosynthesis of pyrimidine nucleotides. A description is given of the crystal
      structure of Lactococcus lactis dihydroorotate dehydrogenase A (DHODA) complexed
      with the product of the enzyme reaction orotate. The structure of the complex to
      2.0 A resolution has been compared with the structure of the native enzyme. The
      active site of DHODA is known to contain a water filled cavity buried beneath a
      highly conserved and flexible loop. In the complex the orotate displaces the
      water molecules from the active site and stacks above the DHODA flavin
      isoalloxazine ring, causing only small movements of the surrounding protein
      residues. The orotate is completely buried beneath the protein surface, and the
      orotate binding causes a significant reduction in the mobility of the active site
      loop. The orotate is bound by four conserved asparagine side chains (Asn 67, Asn
      127, Asn 132, and Asn 193), the side chains of Lys 43 and Ser 194, and the main
      chain NH groups of Met 69, Gly 70, and Leu 71. Of these the Lys 43 side chain
      makes hydrogen bonds to both the flavin isoalloxazine ring and the carboxylate
      group of the orotate. Potential interactions with bound dihydroorotate are
      considered using the orotate complex as a basis for molecular modeling. The role
      of Cys 130 as the active site base is discussed, and the sequence conservation of
      the active site residues across the different families of DHODs is reviewed,
      along with implications for differences in substrate binding and in the catalytic
      mechanisms between these families.

PMID- 9655330
TI  - Circular permutation of betaB2-crystallin changes the hierarchy of domain
      assembly.
AB  - The betagamma-crystallins form a superfamily of eye lens proteins comprised of
      multiple Greek motifs that are symmetrically organized into domains and higher
      assemblies. In the betaB2-crystallin dimer each polypeptide folds into two
      similar domains that are related to monomeric gamma-crystallin by domain
      swapping. The crystal structure of the circularly permuted two-domain betaB2
      polypeptide shows that permutation converts intermolecular domain pairing into
      intramolecular pairing. However, the dimeric permuted protein is, in fact, half a
      native tetramer. This result shows how the sequential order of domains in multi
      domain proteins can affect quaternary domain assembly.

PMID- 9655331
TI  - Crystal structure of cis-biphenyl-2,3-dihydrodiol-2,3-dehydrogenase from a PCB
      degrader at 2.0 A resolution.
AB  - cis-Biphenyl-2,3-dihydrodiol-2,3-dehydrogenase (BphB) is involved in the aerobic
      biodegradation of polychlorinated biphenyls (PCBs). The crystal structure of the
      NAD+-enzyme complex was determined by molecular replacement and refined to an R
      value of 17.9% at 2.0 A. As a member of the short-chain alcohol
      dehydrogenase/reductase (SDR) family, the overall protein fold and positioning of
      the catalytic triad in BphB are very similar to those observed in other SDR
      enzymes, although small differences occur in the cofactor binding site. Modeling
      studies indicate that the substrate is bound in a deep hydrophobic cleft close to
      the nicotinamide moiety of the NAD+ cofactor. These studies further suggest that
      Asn143 is a key determinant of substrate specificity. A two-step reaction
      mechanism is proposed for cis-dihydrodiol dehydrogenases.

PMID- 9655332
TI  - Crystal structure of human cathepsin S.
AB  - We have determined the 2.5 A structure (Rcryst = 20.5%, Rfree = 28.5%) of a
      complex between human cathepsin S and the potent, irreversible inhibitor 4
      morpholinecarbonyl-Phe-hPhe-vinyl sulfone-phenyl. Noncrystallographic symmetry
      averaging and other density modification techniques were used to improve electron
      density maps which were nonoptimal due to systematically incomplete data. Methods
      that reduce the number of parameters were implemented for refinement. The refined
      structure shows cathepsin S to be similar to related cysteine proteases such as
      papain and cathepsins K and L. As expected, the covalently-bound inhibitor is
      attached to the enzyme at Cys 25, and enzyme binding subsites S3-S1' are occupied
      by the respective inhibitor substituents. A somewhat larger S2 pocket than what
      is found in similar enzymes is consistent with the broader specificity of
      cathepsin S at this site, while Lys 61 in the S3 site may offer opportunities for
      selective inhibition of this enzyme. The presence of Arg 137 in the S1' pocket,
      and proximal to Cys 25 may have implications not only for substrate specificity C
      terminal to the scissile bond, but also for catalysis.

PMID- 9655333
TI  - Structure of malonic acid-based inhibitors bound to human neutrophil collagenase.
      A new binding mode explains apparently anomalous data.
AB  - Matrix metalloproteinases (MMPs) are a family of zinc endopeptidases, which have
      been implicated in various disease processes. Various classes of MMP inhibitors,
      including hydroxamic acids, phosphinic acids, and thiols, have been previously
      described. Most of these mimic peptides, and most likely bind analogous to the
      corresponding peptide substrates. Among the hydroxamic acids, malonic acid
      derivatives have been used as MMP inhibitors, although optimization of their
      inhibition potency was not successful. Here we report the design of malonic acid
      based inhibitors using the X-ray structure of a collagenase/inhibitor complex,
      which revealed a nonsubstrate-like binding mode. The proposed beta-type turn-like
      conformation for the improved inhibitors was confirmed by X-ray crystallography.
      The observation of nonsubstrate-like binding confirms the original strategy for
      structure-based modeling of improved malonic acid inhibitors, and explains
      kinetic data that are inconsistent with substrate-like binding. Detailed
      interactions for the improved inhibitors seen in the crystal structure also
      suggest possibilities for further modifications in cycles of structure based drug
      design. Indeed, we have designed nonpeptidic inhibitors with approximately 500
      fold improved inhibition based on these structures.

PMID- 9655334
TI  - Crystal structure of the cyclophilin-like domain from the parasitic nematode
      Brugia malayi.
AB  - Cyclophilins are a family of proteins that exhibit peptidyl-prolyl cis-trans
      isomerase activity and bind the immunosuppressive agent cyclosporin A (CsA).
      Brugia malayi is a filarial nematode parasite of humans, for which a cyclophilin
      like domain was identified at the N-terminal of a protein containing 843 amino
      acid residues. There are two differences in sequence in the highly conserved CsA
      binding site: A histidine and a lysine replace a tryptophan and an alanine,
      respectively. The crystal structure of this domain has been determined by the
      molecular replacement method and refined to an R-factor of 16.9% at 2.15 A
      resolution. The overall structure is similar to other cyclophilins; however,
      major differences occur in two loops. Comparison of the CsA binding site of this
      domain with members of the cyclophilin family shows significant structural
      differences, which can account for the reduced sensitivity of the Brugia malayi
      protein to inhibition by CsA.

PMID- 9655335
TI  - Structural investigation of the A domains of human blood coagulation factor V by
      molecular modeling.
AB  - Factor V (FV) is a large (2,196 amino acids) nonenzymatic cofactor in the
      coagulation cascade with a domain organization (A1-A2-B-A3-C1-C2) similar to the
      one of factor VIII (FVIII). FV is activated to factor Va (FVa) by thrombin, which
      cleaves away the B domain leaving a heterodimeric structure composed of a heavy
      chain (A1-A2) and a light chain (A3-C1-C2). Activated protein C (APC), together
      with its cofactor protein S (PS), inhibits the coagulation cascade via limited
      proteolysis of FVa and FVIIIa (APC cleaves FVa at residues R306, R506, and R679).
      The A domains of FV and FVIII share important sequence identity with the plasma
      copper-binding protein ceruloplasmin (CP). The X-ray structure of CP and
      theoretical models for FVIII have been recently reported. This information
      allowed us to build a theoretical model (994 residues) for the A domains of human
      FV/FVa (residues 1-656 and 1546-1883). Structural analysis of the FV model
      indicates that: (a) the three A domains are arranged in a triangular fashion as
      in the case of CP and the organization of these domains should remain essentially
      the same before and after activation; (b) a Type II copper ion is located at the
      A1-A3 interface; (c) residues R306 and R506 (cleavage sites for APC) are both
      solvent exposed; (d) residues 1667-1765 within the A3 domain, expected to
      interact with the membrane, are essentially buried; (e) APC does not bind to FVa
      residues 1865-1874. Several other features of factor V/Va, like the R506Q and
      A221V mutations; factor Xa (FXa) and human neutrophil elastase (HNE) cleavages;
      protein S, prothrombin and FXa binding, are also investigated.

PMID- 9655336
TI  - Crystal structure of apo-glycine N-methyltransferase (GNMT).
AB  - The crystal structure of the recombinant apo-form of glycine N-methyltransferase
      (GNMT) has been determined at 2.5 A resolution. GNMT is a tetrameric enzyme
      (monomer Mr = 32,423Da, 292 amino acids) that catalyzes the transfer of a methyl
      group from S-adenosylmethionine (AdoMet) to glycine with the formation of S
      adenosylhomocysteine (AdoHcy) and sarcosine (N-methylglycine). GNMT is a
      regulatory enzyme, which is inhibited by 5-methyltetrahydrofolate pentaglutamate
      and believed to control the ratio of AdoMet to AdoHcy in tissues. The crystals
      belong to the orthorhombic space group P2(1)2(1)2 (a = 85.39, b = 174.21, c =
      44.71 A) and contain one dimer per asymmetric unit. The AdoMet-GNMT structure
      served as the starting model. The structure was refined to an R-factor of 21.9%.
      Each monomer is a three-domain structure with a large cavity enclosed by the
      three domains. The tetramer resembles a square with a central channel about which
      N-terminal domains are intertwined. Only localized changes of the residues
      involved in the binding pocket are observed for the apo-GNMT structure when
      compared to that determined in the presence of substrate and substrate analog.

PMID- 9655337
TI  - The three-dimensional structure of a helix-less variant of intestinal fatty acid
      binding protein.
AB  - Intestinal fatty acid-binding protein (I-FABP) is a cytosolic 15.1-kDa protein
      that appears to function in the intracellular transport and metabolic trafficking
      of fatty acids. It binds a single molecule of long-chain fatty acid in an
      enclosed cavity surrounded by two five-stranded antiparallel beta-sheets and a
      helix-turn-helix domain. To investigate the role of the helical domain, we
      engineered a variant of I-FABP by deleting 17 contiguous residues and inserting a
      Ser-Gly linker (Kim K et al., 1996, Biochemistry 35:7553-7558). This variant,
      termed delta17-SG, was remarkably stable, exhibited a high beta-sheet content and
      was able to bind fatty acids with some features characteristic of the wild-type
      protein. In the present study, we determined the structure of the delta17
      SG/palmitate complex at atomic resolution using triple-resonance 3D NMR methods.
      Sequence-specific 1H, 13C, and 15N resonance assignments were established at pH
      7.2 and 25 degrees C and used to define the consensus 1H/13C chemical shift
      derived secondary structure. Subsequently, an iterative protocol was used to
      identify 2,544 NOE-derived interproton distance restraints and to calculate its
      tertiary structure using a unique distance geometry/simulated annealing
      algorithm. In spite of the sizable deletion, the delta17-SG structure exhibits a
      backbone conformation that is nearly superimposable with the beta-sheet domain of
      the wild-type protein. The selective deletion of the alpha-helical domain creates
      a very large opening that connects the interior ligand-binding cavity with
      exterior solvent. Unlike wild-type I-FABP, fatty acid dissociation from delta17
      SG is structurally and kinetically unimpeded, and a protein conformational
      transition is not required. The delta17-SG variant of I-FABP is the only wild
      type or engineered member of the intracellular lipid-binding protein family whose
      structure lacks alpha-helices. Thus, delta17-SG I-FABP constitutes a unique model
      system for investigating the role of the helical domain in ligand-protein
      recognition, protein stability and folding, lipid transfer mechanisms, and
      cellular function.

PMID- 9655338
TI  - Comparative analysis of the noncollagenous NC1 domain of type IV collagen:
      identification of structural features important for assembly, function, and
      pathogenesis.
AB  - Type IV collagen alpha1-alpha6 chains have important roles in the assembly of
      basement membranes and are implicated in the pathogenesis of Goodpasture
      syndrome, an autoimmune disorder, and Alport syndrome, a hereditary renal
      disease. We report comparative sequence analyses and structural predictions of
      the noncollagenous C-terminal globular NC1 domain (28 sequences). The inferred
      tree verified that type IV collagen sequences fall into two groups, alpha1-like
      and alpha2-like, and suggested that vertebrate alpha3/alpha4 sequences evolved
      before alpha1/alpha2 and alpha5/alpha6. About one fifth of NC1 residues were
      identified to confer either the alpha1 or alpha2 group-specificity. These
      residues accumulate opposite charge in subdomain B of alpha1 (positive) and
      alpha2 (negative) sequences and may play a role in the stoichiometric chain
      selection upon type IV collagen assembly. Neural network secondary structure
      prediction on multiple aligned sequences revealed a subdomain core structure
      consisting of six hydrophobic beta-strands and one short alpha-helix with a
      significant hydrophobic moment. The existence of opposite charges in the alpha
      helices may carry implications for intersubdomain interactions. The results
      provide a rationale for defining the epitope that binds Goodpasture
      autoantibodies and a framework for understanding how certain NC1 mutations may
      lead to Alport syndrome. A search algorithm, based entirely on amino acid
      properties, yielded a possible similarity of NC1 to tissue inhibitor of
      metalloproteinases (TIMP) and prompted an investigation of a possible functional
      relationship. The results indicate that NC1 preparations decrease the activity of
      matrix metalloproteinases 2 and 3 (MMP-2, MMP-3) toward a peptide substrate,
      though not to [14C]-gelatin. We suggest that an ancestral NC1 may have been
      incorporated into type IV collagen as an evolutionarily mobile domain carrying
      proteinase inhibitor function.

PMID- 9655339
TI  - Thermodynamic characterization of an intermediate state of human growth hormone.
AB  - The thermal denaturation of recombinant human growth hormone (rhGH) was studied
      by differential scanning calorimetry and circular dichroism spectroscopy (CD).
      The thermal unfolding is reversible only below pH 3.5, and under these conditions
      a single two-state transition was observed between 0 and 100 degrees C. The
      magnitudes of the deltaH and deltaCp of this transition indicate that it
      corresponds to a partial unfolding of rhGH. This is also supported by CD data,
      which show that significant secondary structure remains after the unfolding.
      Above pH 3.5 the thermal denaturation is irreversible due to the aggregation of
      rhGH upon unfolding. This aggregation is prevented in aqueous solutions of
      alcohols such as n-propanol, 2-propanol, or 1,2-propanediol (propylene glycol),
      which suggests that the self-association of rhGH is caused by hydrophobic
      interactions. In addition, it was found that the native state of rhGH is stable
      in relatively high concentrations of propylene glycol (up to 45% v/v at pH 7-8 or
      30% at pH 3) and that under these conditions the thermal unfolding is cooperative
      and corresponds to a transition from the native state to a partially folded
      state, as observed at acidic pH in the absence of alcohols. In higher
      concentrations of propylene glycol, the tertiary structure of rhGH is disrupted
      and the cooperativity of the unfolding decreases. Moreover, the CD and DSC data
      indicate that a partially folded intermediate with essentially native secondary
      structure and disordered tertiary structure becomes significantly populated in 70
      80% propylene glycol.

PMID- 9655340
TI  - Conformational change in the activation of lipase: an analysis in terms of low
      frequency normal modes.
AB  - The interfacial activation of Rhizomucor miehei lipase (RmL) involves the motion
      of an alpha-helical region (residues 82-96) which acts as a "lid" over the active
      site of the enzyme, undergoing a displacement from a "closed" to an "open"
      conformation upon binding of substrate. Normal mode analyses performed in both
      low and high dielectric media reveal that low-frequency vibrational modes
      contribute significantly to the conformational transition between the closed and
      open conformations. In these modes, the lid displacement is coupled to local
      motions of active site loops as well as global breathing motions. Atomic
      fluctuations of the first hinge of the lid (residues 83-84) are substantially
      larger in the low dielectric medium than in the high dielectric medium. Our
      results also suggest that electrostatic interactions of Arg86 play an important
      role in terms of both the intrinsic stability of the lid and its displacement,
      through enhancement of hinge mobility in a high dielectric medium. Additional
      calculations demonstrate that the observed patterns of atomic fluctuations are an
      intrinsic feature of the protein structure and not dependent on the nature of
      specific energy minima.

PMID- 9655341
TI  - Deciphering the structural code for proteins: helical propensities in domain
      classes and statistical multiresidue information in alpha-helices.
AB  - We made several statistical analyses in a large sample of nearly 4,000 helices
      (from 546 redundancy-controlled PDB protein subunits), which give new insights
      into the helical properties of globular proteins. In a first experiment, the
      amino acid composition of the whole sample was compared with the composition of
      two helical sample subgroups (the "mainly-alpha" and the "(alpha/beta)8 barrel"
      domain classes); we reached the conclusion that composition-based helical
      propensities for secondary structure prediction do not depend on the structural
      class. Running a five-residue window through the whole sample, the positional
      composition revealed that positive and negative residues are located throughout
      the helices and tend to neutralize the macrodipole effect. On this basis, we
      analyzed charged triplets using a running five-residue window. The conclusion was
      that only mixed charged residues [positive (+) and negative (-)] located at
      positions 1-2-5 and 1-4-5 are clearly favored. In these locations the most
      abundant are (- -..+) and (-..+ +), and this shows the existence of side chain
      microdipoles, which neutralize the large macrodipole of the helix. We made a
      systematic statistical analysis of charged, dipolar, and hydrophobic + aromatic
      residues, which enabled us to work out rules that should be useful for modeling
      and design purposes. Finally, we analyzed the relative abundance of all the
      different amphipathic double-arcs that are present in helices formed by
      octapeptides (8) and nonapeptides (18). All of the double-arcs that make up
      Schiffer and Edmundson's classical helical wheel are found in abundance in the
      sample.

PMID- 9655342
TI  - Crystal structure of Saccharomyces cerevisiae cytosolic aspartate
      aminotransferase.
AB  - The crystal structure of Saccharomyces cerevisiae cytoplasmic aspartate
      aminotransferase (EC 2.6.1.1) has been determined to 2.05 A resolution in the
      presence of the cofactor pyridoxal-5'-phosphate and the competitive inhibitor
      maleate. The structure was solved by the method of molecular replacement. The
      final value of the crystallographic R-factor after refinement was 23.1% with good
      geometry of the final model. The yeast cytoplasmic enzyme is a homodimer with two
      identical active sites containing residues from each subunit. It is found in the
      "closed" conformation with a bound maleate inhibitor in each active site. It
      shares the same three-dimensional fold and active site residues as the aspartate
      aminotransferases from Escherichia coli, chicken cytoplasm, and chicken
      mitochondria, although it shares less than 50% sequence identity with any of
      them. The availability of four similar enzyme structures from distant regions of
      the evolutionary tree provides a measure of tolerated changes that can arise
      during millions of years of evolution.

PMID- 9655343
TI  - Study of a noncovalent trp repressor: DNA operator complex by electrospray
      ionization time-of-flight mass spectrometry.
AB  - Electrospray ionization time-of-flight mass spectrometry (ESI-TOF MS) has been
      used to study noncovalent interactions between the trp apo-repressor (TrpR), its
      co-repressor tryptophan and its specific operator DNA. In 5 mM ammonium acetate,
      TrpR was detected as a partially unfolded monomer. In the presence of a 21-base
      pair DNA possessing the two symmetrically arranged CTAG consensus sequences
      required for specific TrpR binding, a homodimer-dsDNA complex with a 1:1
      stoichiometry was observed. Co-repressor was not needed for the complex to form
      under our experimental conditions. Collision induced dissociation (CID-MS)
      revealed that this complex was very stable in the gas phase since dissociation
      was achieved only at energies that also broke covalent bonds. We saw no evidence
      for the presence of the six water molecules that mediate the interaction between
      the protein and the DNA in the crystal structure. To check the binding
      specificity of the TrpR for its target DNA, a competitive experiment was
      undertaken: the protein was mixed with an equimolar amount of three different
      DNAs in which the two CTAG sequences were separated by 2, 4, and 6 bp,
      respectively. Only the DNA with the correct consensus spacing of 4 bp was able to
      form stable interactions with TrpR. This experiment demonstrates the potential of
      ESI-MS to test the sequence-specificity of protein-DNA complexes. The
      interactions between the TrpR-DNA complex and 5-methyl-, L- and D-tryptophan were
      also investigated. Two molecules of 5-methyl- or L-tryptophan were bound with
      high affinity to the TrpR-DNA complex. On the other hand, D-tryptophan appeared
      to bind to the complex with poor specificity and poor affinity.

PMID- 9655344
TI  - Excluded volume in the configurational distribution of a strongly-denatured
      protein.
AB  - The configurational distribution of phosphoglycerate kinase (PGK) strongly
      denatured in 4 M guanidine hydrochloride solution is investigated using small
      angle neutron scattering (SANS) and Monte Carlo computer simulation. It is shown
      that the experimental scattering profile can be represented by a random flexible
      chain of spheres of excess scattering density with excluded volume interactions,
      the best agreement being achieved when partial sphere intersection is allowed.
      The radius of gyration of the chain increases by a factor of 4 on denaturation,
      whereas the average length of segments approximately 5 residues long increases by
      only approximately 10%, consistent with a picture in which the large expansion on
      denaturation originates primarily from increased long-range flexibility of the
      polypeptide chain. The results provide a description of the chain statistics from
      which the construction of starting points for simulation studies of folding of
      the protein can be envisaged.

PMID- 9655345
TI  - From coiled coils to small globular proteins: design of a native-like three-helix
      bundle.
AB  - A monomolecular native-like three-helix bundle has been designed in an iterative
      process, beginning with a peptide that noncooperatively assembled into an
      antiparallel three-helix bundle. Three versions of the protein were designed in
      which specific interactions were incrementally added. The hydrodynamic and
      spectroscopic properties of the proteins were examined by size exclusion
      chromatography, sedimentation equilibrium, fluorescence spectroscopy, and NMR.
      The thermodynamics of folding were evaluated by monitoring the thermal and
      guanidine-induced unfolding transitions using far UV circular dichroism
      spectroscopy. The attainment of a unique, native-like state was achieved through
      the introduction of: (1) helix capping interactions; (2) electrostatic
      interactions between partially exposed charged residues; (3) a diverse collection
      of apolar side chains within the hydrophobic core.

PMID- 9655346
TI  - Design, total synthesis, and functional overexpression of the Candida rugosa lip1
      gene coding for a major industrial lipase.
AB  - The dimorphic yeast Candida rugosa has an unusual codon usage that hampers the
      functional expression of genes derived from this yeast in a conventional
      heterologous host. Commercial samples of C. rugosa lipase (CRL) are widely used
      in industry, but contain several different isoforms encoded by the lip gene
      family, among which the isoform encoded by the gene lip1 is the most prominent.
      In a first laborious attempt, the lip1 gene was systematically modified by site
      directed mutagenesis to gain functional expression in Saccharomyces cerevisiae.
      As alternative approach, the gene (1647 bp) was completely synthesized with an
      optimized nucleotide sequence in terms of heterologous expression in yeast and
      simplified genetic manipulation. The synthetic gene was functionally expressed in
      both hosts S. cerevisiae and Pichia pastoris, and the effect of heterologous
      leader sequences on expression and secretion was investigated. In particular,
      using P. pastoris cells, the synthetic gene was functionally overexpressed,
      allowing for the first time to produce recombinant Lipl of high purity at a level
      of 150 U/mL culture medium. The physicochemical and catalytic properties of the
      recombinant lipase were compared with those of a commercial, nonrecombinant C.
      rugosa lipase preparation containing lipase isoforms.

PMID- 9655347
TI  - Electrospray-ionization mass spectrometry of intact intrinsic membrane proteins.
AB  - Membrane proteins drive and mediate many essential cellular processes making them
      a vital section of the proteome. However, the amphipathic nature of these
      molecules ensures their detailed structural analysis remains challenging. A
      versatile procedure for effective electrospray-ionization mass spectrometry (ESI
      MS) of intact intrinsic membrane proteins purified using reverse-phase
      chromatography in aqueous formic acid/isopropanol is presented. The spectra of
      four examples, bacteriorhodopsin and its apoprotein from Halobacterium and the D1
      and D2 reaction-center subunits from spinach thylakoids, achieve mass
      measurements that are within 0.01% of calculated theoretical values. All of the
      spectra reveal lesser quantities of other molecular species that can usually be
      equated with covalently modified subpopulations of these proteins. Our analysis
      of bovine rhodopsin, the first ESI-MS study of a G-protein coupled receptor,
      yielded a complex spectrum indicative of extensive molecular heterogeneity. The
      range of masses measured for the native molecule agrees well with the range
      calculated based upon variable glycosylation and reveals further heterogeneity
      arising from other covalent modifications. The technique described represents the
      most precise way to catalogue membrane proteins and their post-translational
      modifications. Resolution of the components of protein complexes provides
      insights into native protein/protein interactions. The apparent retention of
      structure by bacteriorhodopsin during the analysis raises the potential of
      obtaining tertiary structure information using more developed ESI-MS experiments.

PMID- 9655348
TI  - Fold prediction by a hierarchy of sequence, threading, and modeling methods.
AB  - Several fold recognition algorithms are compared to each other in terms of
      prediction accuracy and significance. It is shown that on standard benchmarks,
      hybrid methods, which combine scoring based on sequence-sequence and sequence
      structure matching, surpass both sequence and threading methods in the number of
      accurate predictions. However, the sequence similarity contributes most to the
      prediction accuracy. This strongly argues that most examples of apparently
      nonhomologous proteins with similar folds are actually related by evolution.
      While disappointing from the perspective of the fundamental understanding of
      protein folding, this adds a new significance to fold recognition methods as a
      possible first step in function prediction. Despite hybrid methods being more
      accurate at fold prediction than either the sequence or threading methods, each
      of the methods is correct in some cases where others have failed. This partly
      reflects a different perspective on sequence/structure relationship embedded in
      various methods. To combine predictions from different methods, estimates of
      significance of predictions are made for all methods. With the help of such
      estimates, it is possible to develop a "jury" method, which has accuracy higher
      than any of the single methods. Finally, building full three-dimensional models
      for all top predictions helps to eliminate possible false positives where
      alignments, which are optimal in the one-dimensional sequences, lead to
      unsolvable sterical conflicts for the full three-dimensional models.

PMID- 9655349
TI  - Formation and properties of mixed disulfides between thioredoxin reductase from
      Escherichia coli and thioredoxin: evidence that cysteine-138 functions to
      initiate dithiol-disulfide interchange and to accept the reducing equivalent from
      reduced flavin.
AB  - Mutation of one of the cysteine residues in the redox active disulfide of
      thioredoxin reductase from Escherichia coli results in C135S with Cys138
      remaining or C138S with Cys135 remaining. The expression system for the genes
      encoding thioredoxin reductase, wild-type enzyme, C135S, and C138S has been re
      engineered to allow for greater yields of protein. Wild-type enzyme and C135S
      were found to be as previously reported, whereas discrepancies were detected in
      the characteristics of C138S. It was shown that the original C138S was a
      heterogeneous mixture containing C138S and wild-type enzyme and that enzyme
      obtained from the new expression system is the correct species. C138S obtained
      from the new expression system having 0.1% activity and 7% flavin fluorescence of
      wild-type enzyme was used in this study. Reductive titrations show that, as
      expected, only 1 mol of sodium dithionite/mol of FAD is required to reduce C138S.
      The remaining thiol in C135S and C138S has been reacted with 5,5'-dithiobis-(2
      nitrobenzoic acid) to form mixed disulfides. The half time of the reaction was <5
      s for Cys138 in C135S and approximately 300 s for Cys135 in C138S showing that
      Cys138 is much more reactive. The resulting mixed disulfides have been reacted
      with Cys32 in C35S mutant thioredoxin to form stable, covalent adducts C138S-C35S
      and C135S-C35S. The half times show that Cys138 is approximately fourfold more
      susceptible to attack by the nucleophile. These results suggest that Cys138 may
      be the thiol initiating dithiol-disulfide interchange between thioredoxin
      reductase and thioredoxin.

PMID- 9655350
TI  - In vivo acetylation identified at lysine 70 of human lens alphaA-crystallin.
AB  - Posttranslational modification of protein lysyl residues that change the net
      charge of the molecule may alter the protein conformation. Such modifications are
      of particular significance among lens proteins, because conformational changes
      are associated with the development of cataract. A previously unidentified
      acetylated form of alphaA-crystallin has been isolated from the water-soluble
      portion of human lenses. The alphaA-crystallins were fractionated by anion
      exchange HPLC into seven peaks, each containing more than one form of alphaA
      crystallin. The previously reported deamidated and phosphorylated forms were
      identified by their molecular masses, determined by electrospray ionization mass
      spectrometry. In addition to these modifications, approximately 5% of alphaA
      crystallin had a modification that decreased the charge by one and increased the
      molecular mass by 42 u. This modification, identified as acetylation, was located
      uniquely at Lys 70. Like any modification that alters the surface charge,
      acetylation may affect protein conformation and intermolecular interactions,
      thereby altering the solubility or chaperone properties of alphaA-crystallin.
      Acetylation of lysine 70 is potentially significant since it is located in a
      region that has been implicated in the chaperone activity of alphaA-crystallin.

PMID- 9655351
TI  - Prediction of functional residues in water channels and related proteins.
AB  - In this paper, we present an updated classification of the ubiquitous MIP (Major
      Intrinsic Protein) family proteins, including 153 fully or partially sequenced
      members available in public databases. Presently, about 30 of these proteins have
      been functionally characterized, exhibiting essentially two distinct types of
      channel properties: (1) specific water transport by the aquaporins, and (2) small
      neutral solutes transport, such as glycerol by the glycerol facilitators.
      Sequence alignments were used to predict amino acids and motifs discriminant in
      channel specificity. The protein sequences were also analyzed using statistical
      tools (comparisons of means and correspondence analysis). Five key positions were
      clearly identified where the residues are specific for each functional subgroup
      and exhibit high dissimilar physico-chemical properties. Moreover, we have found
      that the putative channels for small neutral solutes clearly differ from the
      aquaporins by the amino acid content and the length of predicted loop regions,
      suggesting a substrate filter function for these loops. From these results, we
      propose a signature pattern for water transport.

PMID- 9655352
TI  - Guanidine hydrochloride unfolding of a transmembrane beta-strand in FepA using
      site-directed spin labeling.
AB  - We have used the electron spin resonance (ESR) site-directed spin-labeling (SDSL)
      technique to examine the guanidine hydrochloride (Gdn-HCl) induced denaturation
      of several sites along a transmembrane beta-strand located in the ferric
      enterobactin receptor, FepA. In addition, we have continued the characterization
      of the beta-strand previously identified by our group (Klug CS et al., 1997,
      Biochemistry 36:13027-13033) to extend from the periplasm to the extracellular
      surface loop in FepA, an integral membrane protein containing a beta-barrel motif
      comprised of a series of antiparallel beta-strands that is responsible for
      transport of the iron chelate, ferric enterobactin (FeEnt), across the outer
      membrane of Escherichia coli and many related enteric bacteria. We have
      previously shown that a large surface loop in FepA containing the FeEnt binding
      site denatures independently of the beta-barrel domain (Klug CS et al., 1995,
      Biochemistry 34:14230-14236). The SDSL approach allows examination of the
      unfolding at individual residues independent of the global unfolding of the
      protein. This work shows that sites along the beta-strand that are exposed to the
      aqueous lumen of the channel denature more rapidly and with higher cooperativity
      than the surface loop, while sites on the hydrophobic side of the beta-strand
      undergo a limited degree of noncooperative unfolding and do not fully denature
      even at high (e.g., 4 M) Gdn-HCl concentrations. We conclude that, in a
      transmembrane beta-strand, the local environment of a given residue plays a
      significant role in the loss of structure at each site.

PMID- 9655353
TI  - Structure and distribution of pentapeptide repeats in bacteria.
AB  - We report the discovery of a novel family of proteins, each member contains
      tandem pentapeptide (five residue) repeats, described by the motif A(D/N)LXX.
      Members of this family are both membrane bound and cytoplasmic. The function of
      these repeats is uncertain, but they may have a targeting or structural function
      rather than enzymatic activity. This family is most common in cyanobacteria,
      suggesting a function related to cyanobacterial-specific metabolism. Although no
      experimental information is available for the structure of this family, it is
      predicted that the tandem pentapeptide repeats will form a right-handed beta
      helical structure. A structural model of the pentapeptide repeats is presented.

PMID- 9655354
TI  - Developmental changes in carbonic anhydrase II in the rat kidney.
AB  - We examined the distribution and maturational changes of carbonic anhydrase I
      (CAI) and carbonic anhydrase II (CAII) in microdissected nephron segments of
      Sprague-Dawley rats. CAI and CAII proteins were measured by enzyme-linked
      immunosorbent assay. CAI was not detected in any nephron segment in 7-week-old
      rats. CAII was present in the collecting ducts, proximal tubules, and thick
      ascending limbs of loop of Henle in 7-week-old rats. CAII contents were
      significantly higher in the early proximal tubules (S1) than in second (S2) and
      late (S3) portions of the proximal tubules, while the contents in S1 were less
      than in cortical collecting ducts (CCD), outer stripe and inner stripes of the
      outer medullary collecting ducts (OMCDo and OMCDi). CAII content in each of S1,
      CCD, and OMCD of 1-week-old rats was only 14% or less of that of adults, but
      increased steeply during the 2nd and 3rd weeks of life, reaching almost 40% at 3
      weeks of age and 97% at 7 weeks. Our results indicate that CAII is present
      throughout the entire nephron of the rat, and that CAII content in S1, CCD, and
      OMCD increases exponentially during the first 7 weeks of life. Our data suggest
      that the immature low levels of CAII may explain, at least in part, the limited
      capacity of urinary acidification during neonatal life. Further studies are
      necessary to establish the role of such changes in CAII content in acid-base
      homeostasis during neonatal life.

PMID- 9655355
TI  - Chronology of renal scarring in males with Alport syndrome.
AB  - We investigated the onset of renal scarring in 62 males (aged 4-26 years) with
      Alport syndrome by measuring cortical interstitial volume fraction [Vv
      (interstitium/cortex)] and percentage global glomerular sclerosis in kidney
      biopsies. Male pediatric (n = 9) and adult (n = 7) donor kidneys served as
      controls. Creatinine clearance at the time of biopsy was available for 43 Alport
      patients. A statistically insignificant correlation between age and Vv
      (interstitium/cortex) was observed in normal subjects (r = +0.47, slope = 0.0009,
      P = 0.07). In the Alport patients, age was significantly correlated with Vv
      (interstitium/cortex (r = +0.49, slope = 0.01, P = 0.001) and global glomerular
      sclerosis (r = +0.41, P = 0.01), and inversely correlated with creatinine
      clearance (r = -0.33, P = 0.04). Creatinine clearance was inversely correlated
      with Vv (interstitium/cortex) (r = -0.78, P = 0.001) and global glomerular
      sclerosis (r = -0.74, P = 0.001). The correlation with creatinine clearance was
      especially strong for Vv (interstitium/cortex) values above the normal range,
      i.e., > 0.2 (r = -0.82, P = 0.001), and was absent for Vv (interstitium/cortex) <
      0.2 (r = -0.119, P = 0.55). Creatinine clearance values less than 80 ml/min per
      1.73 m2 occurred more frequently in patients with Vv (interstitium/cortex) values
      > 0.2 (P < 0.0001) and in patients with > 10% globally sclerosed glomeruli (P <
      0.001). Patients < or = or > 10 years of age differed in Vv (interstitium/cortex)
      [0.13 +/- 0.09 (mean +/- SD) vs. 0.24 +/- 0.026, P < 0.001], the frequency of Vv
      (interstitium/cortex) > 0.2 (3/32 vs. 15/31, P < 0.0001), the frequency of > 10%
      globally sclerosed glomeruli (3/33 vs. 11/30, P < 0.05), mean creatinine
      clearance (113 +/- 7 vs. 84 +/- 10 ml/min per 1.73 m2, P = 0.057), and the
      frequency of creatinine clearance < 80 ml/min per 1.73 m2 (1/20 vs. 11/23, P <
      0.01). Thus, reduced creatinine clearance in males with Alport syndrome is
      associated with Vv (interstitium/cortex) > 0.2 and > 10% globally sclerosed
      glomeruli. These are frequently detectable in the 2nd decade. We hypothesize that
      most Alport males will require intervention during the 1st decade for optimal
      preservation of kidney function.

PMID- 9655356
TI  - Urinary excretion substances in patients with cystic fibrosis: risk of
      urolithiasis?
AB  - Patients with cystic fibrosis (CF) have an increased risk of
      urolithiasis/nephrocalcinosis. To determine potential mechanisms responsible, we
      studied the urinary excretion of lithogenic and stone-inhibitory substances and
      calculated the urinary saturation for calcium-oxalate (CaOx), brushite (CaHPO4),
      and uric acid (UA). We examined 24-h urines in 63 patients with CF (34 female, 29
      male) aged 5 months to 36 years. Renal ultrasonography was performed at the time
      of urine collection. Hyperoxaluria was found in 25 patients (range 0.51-1.71
      mmol/1.73 m2 per 24 h). Urinary Ca was increased in 13 patients (4.1-8.22 mg/kg
      per 24 h). Hyperuricosuria was found in 16 patients (5.2-18.0 mmol/1.73 m2 per 24
      h) and hypocitraturia in 14 patients (0.07-1.14 mmol/1.73 m2 per 24 h). CaOx
      saturation was elevated in 26 patients, related to hyperoxaluria in 19 patients.
      CaHPO4 saturation was increased in 19 patients and UA saturation in 11 patients.
      Urolithiasis in situ was diagnosed in 1 patient; 3 patients previously had renal
      stones; 4 patients had present nephrocalcinosis. Elevated excretion of lithogenic
      substances and urinary supersaturation might lead to the higher risk of
      urolithiasis/nephrocalcinosis in patients with CF.

PMID- 9655357
TI  - Renal tubular function in beta-thalassemia.
AB  - Studies of the renal involvement in thalassemic syndromes have been varied and
      few. This study was designed to define the renal abnormalities associated with
      beta-thalassemia and to correlate the renal findings with clinical parameters.
      One hundred and four beta-thalassemic children with various disease severity were
      studied. The patients were divided into three groups: 48 with severe anemia
      [hematocrit (Hct) < 25%], 31 on a hypertransfusion program and desferrioxamine
      treatment, and 25 with moderate anemia (Hct > 25%). The results were compared
      with 15 normal children. Significantly higher levels of proteinuria and low
      molecular weight proteinuria were found in all patients compared with normal
      children. Aminoaciduria was detected in one-third of patients. Thalassemic
      patients had significantly lower morning urine osmolarity, higher urine N-acetyl
      beta-D-glucoseminidase and malondialdehyde (MDA, an indicator of lipid
      peroxidation). Patients with severe anemia had significantly higher low-molecular
      weight proteinuria and MDA, and lower urine osmolarity than those with moderate
      anemia. Our data confirmed the high frequency of renal abnormalities in beta
      thalassemia patients and indicated some degree of proximal tubular dysfunction.
      Severity of the abnormalities correlated with the degree of anemia and were least
      severe in patients on hypertransfusion and desferrioxamine therapy. This
      suggested that the damage might be caused by anemia and increased oxidation
      induced by excess iron deposits.

PMID- 9655358
TI  - Vincristine and focal segmental sclerosis: do we need a multicentre trial?
AB  - Over the last 10 years, eight children have received vincristine for the
      treatment of steroid- and cyclophosphamide-resistant nephrotic syndrome at Great
      Ormond Street Hospital for Children, London. We present our experience of these
      eight cases and put forward a case for reassessing the effectiveness of
      vincristine in this disorder. In our series, two children treated with
      vincristine achieved complete remission with preserved renal function, including
      relapses in one. Both had primary steroid- and cyclophosphamide-resistant focal
      segmental glomerulo sclerosis (FSGS). Of the other cases, four also had primary
      FSGS, one familial FSGS and one mesangioproliferative glomerulonephritis. We
      discuss in general the pros and cons of vincristine therapy in nephrotic syndrome
      versus the cytotoxic agents that are currently used and the differences in
      clinical features among the responders and non-responders in this small group. In
      addition, we explore why this may have occurred and summarise the literature over
      the last 25 years, where vincristine appeared to have been beneficial, especially
      in secondary forms of nephrotic syndrome associated with malignancy. We conclude
      that vincristine therapy warrants re-examination as it could be a valuable
      alternative therapeutic agent in some cases of FSGS with relatively minor side
      effects.

PMID- 9655359
TI  - Albumin, IgG, retinol-binding protein, and alpha1-microglobulin excretion in
      childhood.
AB  - Urine concentrations of two high molecular weight proteins, albumin and IgG, and
      two low molecular weight proteins, alpha1-microglobulin (A1M) and retinol-binding
      protein (RBP), were measured in 657 healthy children from birth to 18 years of
      age. The urinary levels of RBP and A1M suggest an age-dependent decline, whereas
      the levels of albumin and IgG show an uneven distribution. Reference values for
      albumin, IgG, A1M, and RBP for each group are reported.

PMID- 9655360
TI  - Successful renal transplantation in Jeune syndrome type 2.
AB  - Jeune syndrome (asphyxiating thoracic dystrophy) is a rare inherited disease
      which is fatal in early childhood in 70% of cases. Severe renal involvement may
      occur and lead to chronic renal insufficiency in patients who survive respiratory
      failure. Therefore the opportunity to perform kidney transplantation is quite
      rare. We report a successful cadaver renal transplantation in a 10-year-old boy
      with Jeune syndrome type 2.

PMID- 9655361
TI  - Technetium-99m-dimercaptosuccinic acid renal scintigraphy in children over 5
      years.
AB  - We retrospectively evaluated the frequency of renal scintigraphic abnormalities
      in children over 5 years admitted with a first symptomatic urinary tract
      infection (UTI). Among 261 children investigated, we found only 23 over 5 years
      having had technetium-99m-dimercaptosuccinic acid scintigraphy during the acute
      phase of a first UTI. Obvious scintigraphic abnormalities were detected in 14
      children (15 kidneys): 12 kidneys showed focal cortical defects and 3 were small
      and deformed. Ultrasound was normal in 7 of the 15 kidneys with abnormal
      scintigraphy and in all the kidneys with normal scintigraphy. Among the 12
      kidneys with focal cortical lesions, 8 kidneys returned to normal or improved
      considerably 2-12 months after initial work-up. In conclusion, in children over 5
      years admitted with a first symptomatic UTI, the frequency of scintigraphic
      abnormalities is high and a strategy based only on ultrasound data would miss
      about 50% of the abnormal kidneys.

PMID- 9655362
TI  - Effect of hyperparathyroidism on response to erythropoietin in children on
      dialysis.
AB  - The response to recombinant human erythropoietin (rHuEPO), 50 units/kg thrice
      weekly, was studied prospectively in 17 children and adolescents with end-stage
      renal disease who were either transfusion dependent or had hematocrits < 25%. For
      convenience, rHuEPO was given intravenously to 12 hemodialysis (HD) patients and
      subcutaneously to 5 peritoneal dialysis (PD) patients. Blood pressure,
      hematocrit, iron indices, and serum potassium, calcium, phosphorus, alkaline
      phosphatase, urea nitrogen, and intact parathyroid hormone (PTH) were monitored
      serially. When serum ferritin was < 100 ng/ ml during therapy, 6 patients
      received iron supplementation. rHuEPO therapy eliminated frequent transfusions in
      all patients; 11 of 17 patients reached the target hematocrit of 30%-33% by week
      16 of rHuEPO, 50 units/kg thrice weekly. The 5 PD patients treated subcutaneously
      reached target at week 6 +/- 1; 6 HD patients treated intravenously reached
      target at week 11 +/- 3; 6 additional HD patients never reached target at this
      dose; 5 of 6 had pre-rHuEPO serum PTH levels >400 pg/ml, significantly higher
      than those of the other patients (P < 0.005); 3 of 6 later reached a hematocrit
      of 30%-33% after the rHuEPO dose was increased to 120-130 units/kg thrice weekly.
      We conclude that most pediatric dialysis patients can be treated successfully
      with rHuEPO, 50 units/kg thrice weekly, unless the serum PTH concentration is
      markedly elevated, in which case a higher dose is likely to be needed.

PMID- 9655363
TI  - Recombinant human growth hormone treatment of children on hemodialysis. French
      Society of Pediatric Nephrology.
AB  - Forty-two children, aged 2-21.5 years on hemodialysis with a height below -2.0
      standard deviation score (SDS) for age, were selected to receive recombinant
      human growth hormone (rhGH) therapy at 17 French centers. Of the 42 children, 36
      were prepubertal and 8 were in early puberty (testicular volume between 4 and 8
      ml for boys, breast development B2 or B3 in girls). All received 1 IU/kg per week
      by daily subcutaneous injection for 1-5 years. The year before rhGH therapy
      served as a control period. During the 1st year of treatment, mean growth
      velocity increased from 3.5 to 7.0 cm/year (P < 0.0001) and was always over 2.5
      cm/year. This velocity allowed a catch-up growth of +0.5 height SDS. Neither
      weight nor the body mass index varied compared with the pretreatment year. No
      change was observed in urea, creatinine, or glucose tolerance. The mean increment
      in bone age was 0.9 years. The mean growth velocity decreased over subsequent
      years (P < 0.0001), but remained higher than the prestudy velocity. A significant
      negative correlation was observed during the 1st year between the increase in
      growth velocity and the prestudy velocity (P < 0.0001), with the least gain in
      patients who had the best spontaneous velocity. Pubertal status had no influence
      on response to rhGH. No significant side effects were observed during the 103
      treatment-years. Five patients developed secondary hyperparathyroidism and 1
      suffered from acute pancreatitis, but the relationship with rhGH therapy remains
      uncertain. rhGH therapy appears indicated for children on hemodialysis, even
      though the potential benefits appear somewhat lower for those with a spontaneous
      growth velocity over 6 cm/year.

PMID- 9655364
TI  - Effect of posture on intraperitoneal pressure and peritoneal permeability in
      children.
AB  - The posture of the patient influences both the intraperitoneal pressure (IPP) and
      the peritoneal permeability. We have studied the effects of the supine and the
      upright position in six children. Two peritoneal equilibration tests (PET) of 90
      min dwell time each were performed consecutively, firstly in the supine position
      and then in the upright position. The same amount of dialysate was instilled
      (1,000 ml/m2; isotonic 1.36% dextrose) for each PET. Using the same filling
      volume, the IPP was significantly higher in the upright position (18.4 +/- 4.8 cm
      H2O) than in the supine position (8 +/- 2.4 cm H2O). The mean percentage IPP
      increase was 130% +/- 35%. The decline in glucose resorption rate from the
      dialysate during the PET was significantly lower in the upright position. Despite
      this greater relative loss of osmotic gradient in the upright than the supine
      position, no significant difference in net ultrafiltration was noted after 90 min
      of dwell. The peritoneal equilibration ratio during the PET was lower in the
      upright than the supine position for urea, creatinine, and phosphate. These
      results favor performing peritoneal dialysis in a supine position, both to
      increase dialysis efficiency and to reduce patient discomfort.

PMID- 9655365
TI  - Bartter and related syndromes: the puzzle is almost solved.
AB  - It is now evident that the term Bartter syndrome does not represent a unique
      entity but encompasses a variety of disorders of renal electrolyte transport.
      Application of molecular biology techniques has permitted a better understanding
      of these "Bartter-like syndromes," which at present can be divided into three
      different genetic and clinical entities. Neonatal Bartter syndrome is observed in
      newborn infants and characterized by polyhydramnios, premature delivery, life
      threatening episodes of fever and dehydration during the early weeks of life,
      growth retardation, hypercalciuria, and early-onset nephrocalcinosis. Two
      molecular defects have been identified: either at the gene encoding the renal
      bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) or the gene encoding an ATP
      sensitive inwardly rectifying K channel (ROMK). "Classic" Bartter syndrome is
      mostly observed during infancy and childhood and is characterized clinically by
      polyuria and growth retardation. Nephrocalcinosis is not present. Very recently,
      either deletions or mutations at the gene encoding a renal chloride channel (ClC
      Kb) have been identified. Gitelman syndrome is observed in older children and
      adults presenting with intermittent episodes of muscle weakness and tetany,
      hypokalemia, and hypomagnesemia. Mutations at the gene encoding the thiazide
      sensitive Na-Cl cotransporter have been identified in the majority of patients
      studied. Obviously the validity of this classification must be confirmed in the
      near future when all mutations have been described and genotypic-phenotypic
      correlations are better defined.

PMID- 9655366
TI  - Chronic renal insufficiency in children and adolescents: the 1996 annual report
      of NAPRTCS. North American Pediatric Renal Transplant Cooperative Study.
AB  - The 1996 annual report of the Chronic Renal Insufficiency Arm of the North
      American Pediatric Renal Transplant Cooperative Study (NAPRTCS) summarizes
      descriptive data and highlights important features on 1,725 patients from 130
      centers. This database contains information on patients with an estimated
      glomerular filtration rate (GFR) < or = 75 ml/min per 1.73 m2 as calculated by
      the Schwartz formula, who were treated on or after 1 January 1994. Thus this
      report reflects 2 years of data entry. Analysis of the data revealed that nearly
      two-thirds of patients registered had a structural anomaly. On average, patients
      were 1.5 standard deviations below age- and sex-specific norms for height, and
      0.6 standard deviations below weight norms. Mean serum creatinine for the entire
      group was 2.4 mg/dl and 68% of patients had a baseline GFR of at least 25 ml/min
      per 1.73 m2. The mean hematocrit for all children at registration was 33.3 +/-
      6.3%, and did not vary among age groups. Overall, 30.9% of patients had a
      hematocrit < 30%. Only 12.8% of patients were receiving Epoetin therapy. Although
      still in infancy, the Chronic Renal Insufficiency Arm of the NAPRTCS database in
      providing important insights into this disorder.

PMID- 9655367
TI  - Investigation of girls with urinary tract infection.

PMID- 9655368
TI  - Chronic renal insufficiency and recombinant human growth hormone treatment.

PMID- 9655369
TI  - Distributions of conjugated linoleic acid (CLA) isomers in tissue lipid classes
      of pigs fed a commercial CLA mixture determined by gas chromatography and silver
      ion-high-performance liquid chromatography.
AB  - Pigs were fed a commercial conjugated linoleic acid (CLA) mixture, prepared by
      alkali isomerization of sunflower oil, at 2% of the basal diet, from 61.5 to 106
      kg live weight, and were compared to pigs fed the same basal diet with 2% added
      sunflower oil. The total lipids from liver, heart, inner back fat, and omental
      fat of pigs fed the CLA diet were analyzed for the incorporation of CLA isomers
      into all the tissue lipid classes. A total of 10 lipid classes were isolated by
      three-directional thin-layer chromatography and analyzed by gas chromatography
      (GC) on long capillary columns and by silver-ion high-performance liquid
      chromatography (Ag+-HPLC); cholesterol was determined spectrophotometrically.
      Only trace amounts (<0.1%; by GC) of the 9,11-18:2 cis/trans and trans,trans
      isomers were observed in pigs fed the control diet. Ten and twelve CLA isomers in
      the diet and in pig tissue lipids were separated by GC and Ag+- HPLC,
      respectively. The relative concentration of all the CLA isomers in the different
      lipid classes ranged from 1 to 6% of the total fatty acids. The four major
      cis/trans isomers (18.9% 11 cis,13 trans-18:2; 26.3% 10 trans,12 cis-18:2; 20.4%
      9 cis,11 trans-18:2; and 16.1% 8 trans, 10 cis-18:2) constituted 82% of the total
      CLA isomers in the dietary CLA mixture, and smaller amounts of the corresponding
      cis,cis (7.4%) and trans,trans (10.1%) isomers were present. The distribution of
      CLA isomers in inner back fat and in omental fat of the pigs was similar to that
      found in the diet. The liver triacylglycerols (TAG), free fatty acids (FFA), and
      cholesteryl esters showed a similar pattern to that found in the diet. The major
      liver phospholipids showed a marked increase of 9 cis,11 trans-18:2, ranging from
      36 to 54%, compared to that present in the diet. However, liver
      diphosphatidylglycerol (DPG) showed a high incorporation of the 11 cis,13 trans
      18:2 isomer (43%). All heart lipid classes, except TAG, showed a high content of
      11 cis,13 trans-18:2, which was in marked contrast to results in the liver. The
      relative proportion of 11 cis,13 trans-18:2 ranged from 30% in the FFA to 77% in
      DPG. The second major isomer in all heart lipids was 9 cis,11 trans-18:2. In both
      liver and heart lipids the relative proportions of both 10 trans,12 cis-18:2 and
      8 trans, 10 cis-18:2 were significantly lower compared to that found in the diet.
      The FFA in liver and heart showed the highest content of trans,trans isomers (31
      to 36%) among all the lipid classes. The preferential accumulation of the 11
      cis,13 trans-18:2 into cardiac lipids, and in particular the major phospholipid
      in the inner mitochondrial membrane, DPG, in both heart and liver, appears unique
      and may be of concern. The levels of 11 cis,13 trans-18:2 naturally found in
      foods have not been established.

PMID- 9655370
TI  - Dietary docosahexaenoic acid and immunocompetence in young healthy men.
AB  - The purpose of this study was to examine the effect of dietary docosahexaenoic
      acid (DHA), in the absence of eicosapentaenoic acid, on human immune response
      (IR). A 120-d study with 11 healthy men was conducted at the Metabolic Research
      Unit of the Western Human Nutrition Research Center. Four subjects (control
      group) were fed the stabilization or basal diet (15, 30, and 55% energy from
      protein, fat, and carbohydrate, respectively) throughout the study; the remaining
      seven subjects (DHA group) were fed the basal diet for the first 30 d, followed
      by 6 g DHA/d for the next 90 d. DHA replaced an equivalent amount of linoleic
      acid; the two diets were comparable in their total fat and all other nutrients.
      Both diets were supplemented with 20 mg d-alpha-tocopherol acetate per day.
      Indices of IR were examined on study day 22, 30, 78, 85, 106, and 113. Addition
      of DHA at moderately high levels did not alter the proliferation of peripheral
      blood mononuclear cells cultured with phytohemagglutinin or concanavalin A, or
      the delayed hypersensitivity skin response. Also, additional DHA did not alter
      the number of T cells producing interleukin 2 (IL2), the ratio between the
      helper/suppressor T cells in circulation, or the serum concentrations of
      immunoglobulin G, C3, and interleukin 2 receptor (IL2R). DHA supplementation,
      however, caused a significant (P = 0.0001) decrease in the number of circulating
      white blood cells which was mainly due to a decrease in the number of circulating
      granulocytes. The number of lymphocytes in peripheral circulation was not
      affected by Dietary DHA enrichment, but the percentage of lymphocytes in white
      blood cells increased because of a reduction in granulocyte numbers. None of
      these indices was changed in the control group. Our results show that when total
      fat intake is low and held constant, DHA consumption does not inhibit many of the
      lymphocyte functions which have been reported to be inhibited by fish oil
      consumption.

PMID- 9655371
TI  - The metabolism and n-6/n-3 ratio of essential fatty acids in rats: effect of
      dietary arachidonic acid and a mixture of sesame lignans (sesamin and
      episesamin).
AB  - In this study, we examined the effect of dietary arachidonic acid (AA) and sesame
      lignans on the content and n-6/n-3 ratio of polyunsaturated fatty acid (PUFA) in
      rat liver and the concentrations of triglyceride (TG) and ketone bodies in serum.
      For 4 wk, rats were fed two types of dietary oils: (i) the control oil diet
      groups (CO and COS): soybean oil/perilla oil = 5:1, and (ii) the AA-rich oil
      group (AO and AOS): AA ethyl esters/palm oil/perilla oil = 2:2:1, with (COS and
      AOS) or without (CO and AO) 0.5% (w/w) of sesame lignans. Dietary AA and sesame
      lignans significantly affected hepatic PUFA metabolism. AA content and n-6/n-3
      ratio in the liver were significantly increased in the AO group, despite the
      dietary total of n-6 PUFA being the same in all groups, while AOS diet reduced AA
      content and n-6/n-3 ratio to a level similar to the CO and COS groups. These
      results suggest that (i) dietary AA considerably affects the hepatic profile and
      n-6/n-3 ratio of PUFA, and (ii) dietary sesame lignans reduce AA content and n
      6/n-3 ratio in the liver. In the AO group, the concentration of acetoacetate was
      significantly increased, but the ratio of beta-hydroxybutyrate/acetoacetate was
      decreased. On the other hand, the AO diet increased the concentration of TG in
      serum by almost twofold as compared to other groups. However, the AOS diet
      significantly reduced serum TG level as compared to the AO group. In addition,
      the AOS diet significantly increased the acetoacetate level, but reduced the beta
      hydroxybutyrate/acetoacetate ratio. These results suggest that dietary sesame
      lignans promote ketogenesis and reduce PUFA esterification into TG. This study
      resulted in two findings: (i) sesame lignans inhibited extreme changes of the n
      6/n-3 ratio by reducing hepatic PUFA content, and (ii) the reduction of hepatic
      PUFA content may have occurred because of the effects of sesame lignans on PUFA
      degradation (oxidation) and esterification.

PMID- 9655372
TI  - Psyllium, not pectin or guar gum, alters lipoprotein and biliary bile acid
      composition and fecal sterol excretion in the hamster.
AB  - Different soluble dietary fibers known to alter cholesterol metabolism were fed
      to golden Syrian hamsters, and their specific impact on lipoproteins, biliary
      bile acid profile, and fecal sterol excretion was evaluated. Semipurified diets
      containing 20% fat; 0.12% cholesterol; and 8% of psyllium (PSY); high (hePE) and
      low (lePE) esterified pectin; or high (hvGG) and low (lvGG) viscous guar gum were
      fed for 5 wk. Compared to control, PSY caused a significant reduction in plasma
      cholesterol (2.9 +/- 0.5 vs. 5.5 +/- 0.5 mmol/L), whereas hePE, lePE, hvGG, or
      lvGG had no apparent effect on plasma lipids. Hepatic total and esterified
      cholesterol were substantially decreased with PSY, pectin and guar gum, whereby
      PSY produced the most pronounced effect. Distinctive changes existed in the bile
      acid profile related to the different fibers. In contrast to pectin and guar gum,
      PSY caused a significant increase in the cholate:chenodeoxycholate and the
      glycine:taurine conjugation ratio. Pectin and guar gum did not alter daily fecal
      neutral sterol excretion while PSY caused a 90% increase due to a higher fecal
      output. Daily fecal bile acid excretion and total fecal bile acid concentration
      were significantly increased by PSY, whereas hePE, lePE, hvGG, and lvGG revealed
      no or only minor effects. Taken together, the disparate hypocholesterolemic
      effects of PSY, pectin, and guar gum on cholesterol and bile acid metabolism in
      the hamster are possibly related to different physicochemical properties, e.g.,
      viscosity and susceptibility to fermentation, affecting the fiber-mediated action
      in the intestine.

PMID- 9655374
TI  - Protective effect of a vitamin E analog, phosphatidylchromanol, against oxidative
      hemolysis of human erythrocytes.
AB  - The protective effect of a vitamin E analog, phosphatidylchromanol [1,2-diacyl-sn
      glycero-3-phospho-2'-(hydroxyethyl)-2',5',7',8'-tetrameth yl-6'-hydroxychroman;
      PCh], against oxidative hemolysis of human erythrocytes was examined and was
      compared with those of vitamin E (alpha-tocopherol) and 2,2,5,7,8-pentamethyl-6
      chromanol (PMC). These three compounds at 50 microM protected the erythrocytes
      from hemolysis, when erythrocyte suspension (10%, vol/vol) was incubated with a
      water-soluble radical generator, 2,2'-azobis(2-amidinopropane)-dihydrochloride
      (75 mM). When erythrocyte suspension was oxidized after pretreatment with these
      compounds (50 microM) for 30 min followed by washing, PCh protected about 54% of
      erythrocytes from the hemolysis, while alpha-tocopherol protected only about 16%
      of the cells and PMC did not show any protective effect. During preincubation,
      alpha-tocopherol, PMC, and PCh were incorporated into the cells at the
      concentration of 12.6, 3.7, and 16.3 nmol/mg protein, respectively. Moreover, PCh
      was found in the ghost membrane fraction at a 20% higher level than alpha
      tocopherol, and no PMC was detected in this fraction. These results indicate that
      phosphatidyl group in PCh acts as an excellent carrier of chromanol moiety into
      cells as well as an anchor within membranes more efficiently than phytyl group in
      alpha-tocopherol. PMC seems to be slightly anchored within membranes because of
      the lack of hydrophobic side chain. The excellent antihemolytic activity of PCh
      is likely to be caused by its accumulation within erythrocyte membranes.

PMID- 9655373
TI  - Dietary cyanidin 3-O-beta-D-glucoside increases ex vivo oxidation resistance of
      serum in rats.
AB  - The effect of dietary cyanidin 3-O-beta-D-glucoside (C3G), a typical anthocyanin
      pigment, on the generation of thiobarbituric acid reactive substances (TBARS)
      during serum formation ex vivo and susceptibility of serum to further lipid
      peroxidation was studied in rats. Rats were fed a diet containing C3G (2 g/kg)
      for 14 d. Feeding C3G resulted in a significant decrease in generation of TBARS
      during serum formation. The serum from the C3G-fed group showed a significantly
      lower susceptibility to further lipid peroxidation provoked by 2,2'-azobis(2
      amidinopropane)hydrochloride or Cu2+ than that of the control group. No
      significant differences were observed in serum phospholipid, triglyceride,
      esterified cholesterol, and free fatty acid concentrations between the control
      and the C3G-fed groups. Concentrations of endogenous antioxidants remaining in
      the serum after blood coagulation were not affected by the C3G feeding. These
      results demonstrate that feeding C3G increases the ex vivo oxidation resistance
      of the serum without affecting serum endogenous antioxidant levels, and reduces
      the TBARS generated during serum formation without changing the concentrations of
      serum lipids.

PMID- 9655375
TI  - Mechanism of lower oxidizability of eicosapentaenoate than linoleate in aqueous
      micelles. II. Effect of antioxidants.
AB  - We have reported that the peroxyl radicals derived from methyl eicosapentaenoate
      (20:5n-3) are more polar than those from methyl linoleate (18:2n-6) since the
      former peroxyl radicals have at least two molecules of oxygen in a molecule while
      the latter peroxyl radical has one. This lowers the oxidizability for 20:5n-3 in
      aqueous Triton X-100 micelles by enhancing the termination reaction rate for
      peroxyl radicals and by reducing the rate of propagation since there may be more
      polar peroxyl radicals derived from 20:5n-3 at the surface than within the
      micelle core. In this study, we measured the effect of three antioxidants, di
      tert-butyl-4-methylphenol (BHT), 2,2,5,7,8-pentamethyl-6-chromanol (PMC) and 2
      carboxy-2,5,7,8-tetramethyl-6-chromanol (Trolox), on the oxidation of lipids in
      aqueous micelle. Antioxidants give a clear induction period during oxidation of
      18:2n-6 initiated with a water-soluble radical initiator, and its induction
      length decreases in the order of BHT > PMC > Trolox. This is consistent with the
      proposed location of three antioxidants: being in the core of micelle, at the
      surface, or in aqueous phase, respectively. However, BHT does not inhibit the
      oxidation of 20:5n-3 efficiently, and its rate of oxidation is slower than that
      observed in the oxidation of 18:2n-6, supporting the idea that polar peroxyl
      radicals derived from 20:5n-3 are preferentially located at the surface of the
      micelle. Similar results were obtained when oxidation was initiated with a lipid
      soluble radical initiator except antioxidants had lesser effect on the oxidation
      rate of 20:5n-3.

PMID- 9655376
TI  - Partial purification and characterization of sphingosine N-acyltransferase
      (ceramide synthase) from bovine liver mitochondrion-rich fraction.
AB  - Sphingosine N-acyltransferase (ceramide synthase, E.C. 2.3.1.24) was solubilized
      from bovine liver mitochondrion-rich fraction with n-octyl beta-D-thioglucoside
      as the detergent and partially purified by sequential chromatography on columns
      of DE-32, shingosine affinity, and Sepharose CL-6B. The partially purified
      preparation migrated on SDS-polyacrylamide gel electrophoresis as two major
      protein bands of 62 and 72 kDa. The molecular mass of the enzyme estimated by gel
      filtration was 240-260 kDa, suggesting that the partially purified enzyme is
      present in a subunit form or simply has an aggregative nature. The specific
      activity of the final preparation for the condensation of sphingosine with
      stearoyl-CoA increased by 98.7-fold compared with the starting material. The
      optimal pH value for the ceramide synthesis was 7.5. The partially purified
      enzyme had an apparent Km of 146 microM and a Vmax of 11.1 nmol/min/mg protein
      for stearoyl-CoA. The Km and Vmax values toward sphingosine were 171 microM and
      11.3 nmol/min/mg protein, respectively. Interestingly, sphinganine was also a
      good substrate for this enzyme, and the Km and Vmax values were 144 microM and
      8.5 nmol/min/mg protein, respectively.

PMID- 9655378
TI  - Long-chain alkenes of the haptophytes Isochrysis galbana and Emiliania huxleyi.
AB  - The major alkenes of the haptophytes Isochrysis galbana (strain CCAP 927/14) and
      Emiliania huxleyi (strains CCAP 920/2 and VAN 556) have been identified by
      nuclear magnetic resonance spectroscopy and by mass spectrometric analysis of
      their dimethyl disulfide adducts. The dominant alkene in I. galbana is (22Z)-1
      ,22-hentriacontadiene, with 1,24-hentriacontadiene and 1,24-tritriacontadiene
      present in much lower abundance; (22Z)-1,22-hentriacontadiene also occurs in E.
      huxleyi (strain CCAP 920/2), together with (2Z,22Z)-2,22-hentriacontadliene (the
      major hydrocarbon) and (3Z,22Z)-3,22-hentriacontadiene. Minor abundances of 2,24
      hentriacontadiene and 2,24-tritriacontadiene are also present in this strain. In
      contrast, the dominant alkene in E. huxleyi (strain VAN 556) is (15 E,22E)
      1,16,23-heptatriacontatriene with the related alkatriene 1,15,22
      octatriacontatriene also present and (22Z)-1,22-hentriacontadiene occurring as a
      minor component. From structural relationships (15E,22E)-1,15,22
      heptatriacontatriene is proposed to derive from the same biosynthetic pathway as
      that of the characteristic C37 alkenones which occur in both E. huxleyi and I.
      galbana. The C31 and C33 dienes likely derive from chain extension and
      decarboxylation of (Z)-9-octadecenoic acid or (Z)-7-hexadecenoic acid, using a
      pathway analogous to that elucidated previously in the chlorophyte Botryococcus
      braunii. Therefore, long-chain dienes and trienes, which can co-occur in
      haptophytes, may have distinct biosynthetic pathways.

PMID- 9655377
TI  - N-stearoyl-phosphatidylserine: synthesis and role in divalent-cation-induced
      aggregation and fusion.
AB  - N-Acylphosphatidylserines have been isolated from intact and injured tissues, but
      the participation of such acidic phospholipids in membrane aggregation and fusion
      has not been demonstrated. We have synthesized N-stearoylphosphatidylserine
      (NSPS) and examined divalent-cation-induced aggregation of NSPS-liposomes, which
      leads to membrane destabilization and fusion. The purified lipid was
      characterized by its chromatographic and spectroscopic (infrared and 1H nuclear
      magnetic resonance) properties and by its chemical degradation pattern.
      Aggregation of unilamellar NSPS-liposomes was studied as a function of calcium
      and magnesium concentration. The ability of calcium and magnesium to induce
      vesicle aggregation is higher for phosphatidylserine (PS)-liposomes (threshold
      concentration 1.5 mM for calcium and 4.6 mM for magnesium) than for NSPS
      liposomes (threshold concentration 2.8 mM for calcium and 6.6 mM for magnesium).
      The irreversibility of the aggregation reactions after adding EDTA suggests that
      vesicle fusion might occur in the presence of calcium and magnesium. Preliminary
      studies, based on mixing of both lipid and internal aqueous contents, show that
      fusion rather than aggregation of NSPS-liposomes occurs in the presence of
      calcium ions. The tendency of NSPS-liposomes to aggregate at higher cation
      concentrations than PS-liposomes suggests that N-acylation of phosphatidylserine
      protects the membrane against degenerative damage caused by aggregation and
      fusion.

PMID- 9655379
TI  - Fatty acid composition of bacteria associated with the toxic dinoflagellate
      Ostreopsis lenticularis and with Caribbean Palythoa species.
AB  - The fatty acid composition of a Pseudomonas sp. (Alteromonas) and its host, the
      dinoflagellate Ostreopsis lenticularis, vectors in ciguatera fish poisoning, has
      been studied. The major fatty acids in O. lenticularis were 16:0, 20:5n-3, and
      22:6n-3, but 18:2n-6, 18:3n-3, and 18:n-3 were also identified. In contrast to
      other dinoflagellates, 1 8:5n-3 was not detected in O. lenticularis. Even-chain
      fatty acids such as 9-16:1, 11-18:1, and 13-20:1 predominated in the Pseudomonas
      sp. from O. lenticularis, but 1 6-20% of (E)-11-methyl-12-octadecenoic acid was
      also identified. The chirality of the latter was confirmed by total synthesis
      (28% overall yield) starting from oxacyclotridecan-2-one. The fatty acid
      compositions of two other Pseudomonas species, from the palytoxin-producing
      zoanthids Palythoa mamillosa and P. caribdea, were also studied and were similar
      to that of the Pseudomonas sp. from O. lenticularis. The possibility of using
      some of these fatty acids as chemotaxonomic lipids in identifying marine animals
      that consume toxic dinoflagellates or zoanthids is discussed.

PMID- 9655380
TI  - Epoxidation reactions of unsaturated fatty esters with potassium
      peroxomonosulfate.
AB  - Epoxidation of the double bond in methyl oleate, octadec-11E-en-9-ynoate,
      ricinoleate (12-hydroxy-octadec-9Z-enoate), iso-ricinoleate (9-hydroxy-octadec
      12Z-enoate), and 12-oxo-octadec-9Z-enoate with potassium peroxomonosulfate
      (oxone, 2 KHSO5.KHSO4.K2SO4) in the presence of trifluoroacetone or methyl
      pyruvate gave the corresponding monoepoxy derivatives. Reaction of Oxone with
      methyl linoleate and octadeca-9Z,11E-dienoate furnished the corresponding
      diepoxystearate derivative. Methyl 9,12-dioxo-octadec-10Z-enoate was obtained
      when a C18 furanoid fatty ester (methyl 9,12-epoxy-9,11-octadecadienoate) was
      treated with Oxone. The yield of these reactions was very high (85-99%), and the
      epoxy derivatives were readily isolated by solvent extraction. The products were
      identified by spectroscopic methods.

PMID- 9655381
TI  - Callyspongynes A and B: new polyacetylenic lipids from a southern Australian
      marine sponge, Callyspongia sp.

PMID- 9655382
TI  - Journal prices lead libraries to back less costly initiatives.

PMID- 9655383
TI  - Congress remains upbeat on public genome efforts.

PMID- 9655384
TI  - South Africa's truth commission reveals bioweapons plot.

PMID- 9655385
TI  - New voices displace east/west tensions.

PMID- 9655386
TI  - Combinatorial chemistry in the hunt for medicines.

PMID- 9655387
TI  - SMAD proteins and mammalian anatomy.

PMID- 9655388
TI  - Actin, cofilin and cognition.

PMID- 9655389
TI  - Deadly relic of the Great War.

PMID- 9655390
TI  - Cnidarian homeoboxes and the zootype.

PMID- 9655391
TI  - Nicotine metabolism defect reduces smoking.

PMID- 9655392
TI  - Smad2 role in mesoderm formation, left-right patterning and craniofacial
      development.
AB  - Signalling by the transforming growth factor-beta (TGF-beta) superfamily of
      proteins depends on the phosphorylation and activation of SMAD proteins by
      heteromeric complexes of ligand-specific type I and type II receptors with
      serine/threonine-kinase activity. The vertebrate SMAD family includes at least
      nine members, of which Smad2 has been shown to mediate signalling by activin and
      TGF-beta. In Xenopus, Smad2 can induce dorsal mesoderm, mimicking Vg-1, activin
      and nodal. Here we investigate the function of Smad2 in mammalian development by
      generating two independent Smad2 mutant alleles in mice by gene targeting. We
      show that homozygous mutant embryos fail to form an organized egg cylinder and
      lack mesoderm, like mutant mice lacking nodal or ActRIB, the gene encoding the
      activin type-I receptor. About 20 per cent of Smad2 heterozygous embryos have
      severe gastrulation defects and lack mandibles or eyes, indicating that the gene
      dosage of Smad2 is critical for signalling. Mice trans-heterozygous for both
      Smad2 and nodal mutations display a range of phenotypes, including gastrulation
      defects, complex craniofacial abnormalities such as cyclopia, and defects in left
      right patterning, indicating that Smad2 may mediate nodal signalling in these
      developmental processes. Our results show that Smad2 function is essential for
      early development and for several patterning processes in mice.

PMID- 9655393
TI  - Activation of human aortic smooth-muscle cells is inhibited by PPARalpha but not
      by PPARgamma activators.
AB  - Peroxisome proliferator-activated receptors (PPARs) are key players in lipid and
      glucose metabolism and are implicated in metabolic disorders predisposing to
      atherosclerosis, such as dyslipidaemia and diabetes. Whereas PPARgamma promotes
      lipid storage by regulating adipocyte differentiation, PPARalpha stimulates the
      beta-oxidative degradation of fatty acids. PPARalpha-deficient mice show a
      prolonged response to inflammatory stimuli, suggesting that PPARalpha is also a
      modulator of inflammation. Hypolipidaemic fibrate drugs are PPARalpha ligands
      that inhibit the progressive formation of atherosclerotic lesions, which involves
      chronic inflammatory processes, even in the absence of their atherogenic
      lipoprotein-lowering effect. Here we show that PPARalpha is expressed in human
      aortic smooth-muscle cells, which participate in plaque formation and post
      angioplasty re-stenosis. In these smooth-muscle cells, we find that PPARalpha
      ligands, and not PPARgamma ligands, inhibit interleukin-1-induced production of
      interleukin-6 and prostaglandin and expression of cyclooxygenase-2. This
      inhibition of cyclooxygenase-2 induction occurs transcriptionally as a result of
      PPARalpha repression of NF-kappaB signalling. In hyperlipidaemic patients,
      fenofibrate treatment decreases the plasma concentrations of interleukin-6,
      fibrinogen and C-reactive protein. We conclude that activators of PPARalpha
      inhibit the inflammatory response of aortic smooth-muscle cells and decrease the
      concentration of plasma acute-phase proteins, indicating that PPARalpha in the
      vascular wall may influence the process of atherosclerosis and re-stenosis.

PMID- 9655394
TI  - Modulation of AMPA receptor unitary conductance by synaptic activity.
AB  - Activity-dependent alteration in synaptic strength is a fundamental property of
      the vertebrate central nervous system and is thought to underlie learning and
      memory. The most extensively studied model of activity-dependent synaptic
      plasticity is long-term potentiation (LTP) of glutamate-responsive
      (glutamatergic) synapses, a widespread phenomenon involving multiple mechanisms.
      The best characterized form of LTP occurs in the CA1 region of the hippocampus,
      in which LTP is initiated by transient activation of NMDA (N-methyl-D-aspartate)
      receptors and is expressed as a persistent increase in synaptic transmission
      through AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate) receptors.
      This increase is due, at least in part, to a postsynaptic modification of AMPA
      receptor function; this modification could be caused by an increase in the number
      of receptors, their open probability, their kinetics or their single-channel
      conductance. Here we show that the induction of LTP in the CA1 region of the
      hippocampus is often associated with an increase in single-channel conductance of
      AMPA receptors. This shows that elementary channel properties can be rapidly
      modified by synaptic activity and provides an insight into one molecular
      mechanism by which glutamatergic synapses can alter their strength.

PMID- 9655395
TI  - IgD can largely substitute for loss of IgM function in B cells.
AB  - The mu and delta heavy chains of IgM and IgD, the first antibody isotypes
      expressed during bone-marrow B-cell development, are encoded by a common
      transcription unit. Expression of the mu chain on the surface of late pre-B cells
      allows their further development to immature B cells. Coexpression of the delta
      chain and emigration of the immature B cells to the periphery eventually leads to
      the development of naive mature IgM/IgD double-positive cells. Although IgM is
      important in driving B-cell development, the contribution of IgD is not clear.
      Here we investigate the function of IgD. We generated mice deficient in IgM (IgM
      /- mice) by deleting the mu region in embryonic stem cells. IgM-/- mice showed
      normal B-cell development and maturation, with IgD replacing membrane-bound and
      secretory IgM. Moreover, specific B-cell responses and isotype class switches
      occurred during immunization or infection. In contrast to mice deficient in B
      cells, IgM-/- mice survived infection with vesicular stomatitis virus by
      developing neutralizing immunoglobulins, but they were more susceptible than wild
      type controls with delayed specific immunoglobulin responses. These data lead us
      to conclude that IgD is largely able to substitute for IgM functions.

PMID- 9655396
TI  - Evidence for the shikimate pathway in apicomplexan parasites.
AB  - Parasites of the phylum Apicomplexa cause substantial morbidity, mortality and
      economic losses, and new medicines to treat them are needed urgently. The
      shikimate pathway is an attractive target for herbicides and antimicrobial agents
      because it is essential in algae, higher plants, bacteria and fungi, but absent
      from mammals. Here we present biochemical, genetic and chemotherapeutic evidence
      for the presence of enzymes of the shikimate pathway in apicomplexan parasites.
      In vitro growth of Toxoplasma gondii, Plasmodium falciparum (malaria) and
      Cryptosporidium parvum was inhibited by the herbicide glyphosate, a well
      characterized inhibitor of the shikimate pathway enzyme 5-enolpyruvyl shikimate 3
      phosphate synthase. This effect on T. gondii and P. falciparum was reversed by
      treatment with p-aminobenzoate, which suggests that the shikimate pathway
      supplies folate precursors for their growth. Glyphosate in combination with
      pyrimethamine limited T. gondii infection in mice. Four shikimate pathway enzymes
      were detected in extracts of T. gondii and glyphosate inhibited 5-enolpyruvyl
      shikimate 3-phosphate synthase activity. Genes encoding chorismate synthase, the
      final shikimate pathway enzyme, were cloned from T. gondii and P. falciparum.
      This discovery of a functional shikimate pathway in apicomplexan parasites
      provides several targets for the development of new antiparasite agents.

PMID- 9655397
TI  - Regulation of actin dynamics through phosphorylation of cofilin by LIM-kinase.
AB  - Cell division, cell motility and the formation and maintenance of specialized
      structures in differentiated cells depend directly on the regulated dynamics of
      the actin cytoskeleton. To understand the mechanisms of these basic cellular
      processes, the signalling pathways that link external signals to the regulation
      of the actin cytoskeleton need to be characterized. Here we identify a pathway
      for the regulation of cofilin, a ubiquitous actin-binding protein that is
      essential for effective depolymerization of actin filaments. LIM-kinase 1, also
      known as KIZ, is a protein kinase with two amino-terminal LIM motifs that induces
      stabilization of F-actin structures in transfected cells. Dominant-negative LIM
      kinasel inhibits the accumulation of the F-actin. Phosphorylation experiments in
      vivo and in vitro provide evidence that cofilin is a physiological substrate of
      LIM-kinase 1. Phosphorylation by LIM-kinase 1 inactivates cofilin, leading to
      accumulation of actin filaments. Constitutively active Rac augmented cofilin
      phosphorylation and LIM-kinase 1 autophosphorylation whereas phorbol ester
      inhibited these processes. Our results define a mechanism for the regulation of
      cofilin and hence of actin dynamics in vivo. By modulating the stability of actin
      cytoskeletal structures, this pathway should play a central role in regulating
      cell motility and morphogenesis.

PMID- 9655398
TI  - Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin
      reorganization.
AB  - Rac is a small GTPase of the Rho family that mediates stimulus-induced actin
      cytoskeletal reorganization to generate lamellipodia. Little is known about the
      signalling pathways that link Rac activation to changes in actin filament
      dynamics. Cofilin is known to be a potent regulator of actin filament dynamics,
      and its ability to bind and depolymerize actin is abolished by phosphorylation of
      serine residue at 3; however, the kinases responsible for this phosphorylation
      have not been identified. Here we show that LIM-kinase 1 (LIMK-1), a
      serine/threonine kinase containing LIM and PDZ domains, phosphorylates cofilin at
      Ser 3, both in vitro and in vivo. When expressed in cultured cells, LIMK-1
      induces actin reorganization and reverses cofilin-induced actin depolymerization.
      Expression of an inactive form of LIMK-1 suppresses lamellipodium formation
      induced by Rac or insulin. Furthermore, insulin and an active form of Rac
      increase the activity of LIMK-1. Taken together, our results indicate that LIMK-1
      participates in Rac-mediated actin cytoskeletal reorganization, probably by
      phosphorylating cofilin.

PMID- 9655399
TI  - Structure of a heparin-linked biologically active dimer of fibroblast growth
      factor.
AB  - The fibroblast growth factors (FGFs) form a large family of structurally related,
      multifunctional proteins that regulate various biological responses. They mediate
      cellular functions by binding to transmembrane FGF receptors, which are protein
      tyrosine kinases. FGF receptors are activated by oligomerization, and both this
      activation and FGF-stimulated biological responses require heparin-like molecules
      as well as FGF. Heparins are linear anionic polysaccharide chains; they are
      typically heterogeneously sulphated on alternating L-iduronic and D-glucosamino
      sugars, and are nearly ubiquitous in animal tissues as heparan sulphate
      proteoglycans on cell surfaces and in the extracellular matrix. Although several
      crystal structures have been described for FGF molecules in complexes with
      heparin-like sugars, the nature of a biologically active complex has been unknown
      until now. Here we describe the X-ray crystal structure, at 2.9 A resolution, of
      a biologically active dimer of human acidic FGF in a complex with a fully
      sulphated, homogeneous heparin decassacharide. The dimerization of heparin-linked
      acidic FGF observed here is an elegant mechanism for the modulation of signalling
      through combinatorial homodimerization and heterodimerization of the 12 known
      members of the FGF family.

PMID- 9655400
TI  - Endoscopic excision and repair of simulated bilateral cleft lips in fetal lambs.
AB  - The use of nonpenetrating clips to accomplish wound closure as an alternative to
      suture in the repair of simulated cleft lips in partially exteriorized fetuses
      has been described previously. In this study, the fetus is approached
      endoscopically, and clipped (n = 8) and sutured (n = 4) intrauterine endoscopic
      repairs in six lambs (90- to 95-day gestation) are compared. Also used was a
      newly developed harmonic scalpel to create the defects in the fluid environment.
      Clipped repairs were nearly 10 times faster than sutured repairs (2.7 +/- 0.5
      minutes compared with 24 +/- 4 minutes, respectively). Furthermore, suture
      incited foreign body inflammation, recruited monocytic inflammatory cells, and
      exhibited notable scarring. The comparison between clipped and sutured repairs
      extends the previous observations to the realm of endoscopy and reinforces the
      previous conclusions of this group that the nonpenetrating clip is more rapid and
      incites less inflammation than suture in fetal wound approximation and repair.

PMID- 9655401
TI  - Decreasing the perioperative complications associated with the superior
      pharyngeal flap operation.
AB  - This outcome study was a continuation of a previously published review. It
      examined whether there had been a decrease in the number of acute perioperative
      complications surrounding superior pharyngeal flap operations since a patient's
      death in 1990. A total of 386 patients were divided into two groups: the early
      group (July of 1985 to December of 1990) n = 164, and the later group (January of
      1991 to June of 1996) n = 222, which were statistically comparable. The patient
      complication rate decreased from 19.5 to 6.3 percent (chi square, p = 0.0001).
      Airway obstruction decreased from 11 to 3.2 percent (chi square, p = 0.0012).
      Bleeding complications decreased from 7.3 to 1.4 percent (chi square, p =
      0.0027). The majority of airway complications (72 percent) and bleeding
      complications (80 percent) occurred in the first 24 hours. Predictive factors for
      complications included the surgeon involved, patients with associated medical
      conditions, having an associated procedure performed concurrently, and leaving
      the donor site open (multiple logistic regression). Hospital stay also decreased
      from 5.8 +/- 2.5 to 3.8 +/- 1.6 days (Student's t test p = 0.0001). The decrease
      in complication rate was due to the increased awareness of all staff involved and
      also due to changes in surgical management, including a decrease in the number of
      surgeons (from seven to four surgeons), a decrease in the number of associated
      procedures (10.4 to 4.5 percent, chi square, p = 0.026), a decrease in the number
      of open donor sites (34.8 to 4.5 percent, chi square, p = 0), and an increase in
      the use of nasopharyngeal airways (17.1 to 45 percent, chi square, p = 0). The
      superior pharyngeal flap operation has become a safer procedure in this hospital.

PMID- 9655402
TI  - Periorbital melanocytic lesions: excision and reconstruction in 40 patients.
AB  - The treatment of melanoma arising in the periorbital region is a difficult
      reconstructive problem. The abundance of vital structures in close proximity to
      one another makes the resection and subsequent reconstructive procedures
      extremely challenging. Reported here is experience with periorbital melanocytic
      lesions in 40 patients with the emphasis on the types of reconstruction
      performed. Forty patients with periorbital melanocytic lesions were treated
      between 1984 and 1995. The periorbital region was subdivided into five zones.
      These zones are the following: zone I, upper eyelid; zone II, lower eyelid; zone
      III, medial canthus; zone IV, lateral canthus; and zone V, contiguous structures.
      Ocular melanomas were not included in this study. The distribution of the lesions
      in our 40 patients was zone I (n = 1), zone II (n = 14), zone III (n = 1), zone
      IV (n = 9), and zone V (n = 31). The ages of the patients ranged from 3 to 84
      years at the time of reconstruction, with an average age of 57 years. Resection
      and reconstruction were performed simultaneously in all patients. Thirty-six of
      the patients were reconstructed with one procedure, three patients required two
      procedures, and one patient required five procedures. The tumor type was
      superficial spreading melanoma in 15 patients, melanoma in situ in 17 patients,
      malignant spindle cell neoplasm in 2 patients, desmoplastic melanoma in 2
      patients, amelanocytic melanoma in 1 patient, epithelioid melanoma in 1 patient,
      and atypical melanocytic nevus in 2 patients in which an early, evolving melanoma
      could not be excluded. Elective lymph node dissection was performed in four
      patients for intermediate thickness lesions (1.5 to 4.0 mm). The types of
      reconstructions performed included full-thickness skin grafts, upper lid
      myocutaneous flaps, cheek advancement flaps, cervicofacial flaps, inferiorly
      based nasolabial flaps, tarsoconjunctival flaps, frontalis muscle flaps, medial
      transposition Z-plasty, and primary closure. The resection of periorbital
      melanomas can be difficult because of the number of important anatomic structures
      in the region. The challenge to the surgeon in handling head and neck melanomas
      in general lies in the need to provide the best functional and aesthetic result
      while still resecting the primary lesion with the intent of effecting a cure. We
      present our series to demonstrate that the adequacy of margins of resection need
      not be compromised to facilitate reconstruction and that excellent results are
      obtainable with reconstructive procedures performed after adequate resections.
      Several different types of flaps and grafts can be used, with the indications
      varying depending on the location of the lesion and the extent of resection. The
      major reconstructive options will be reviewed in detail.

PMID- 9655403
TI  - Pediatric facial fractures: analysis of differences in subspecialty care.
AB  - At the University of Michigan, the pediatric facial fracture call schedule
      rotates through the plastic surgery, otolaryngology, and oral surgery services.
      This situation provides an opportunity to evaluate differences in the management
      of pediatric facial fractures between subspecialty groups. At this hospital, a
      retrospective review of all pediatric facial fracture cases within a 5-year
      period was undertaken. Sixty patients with 82 facial fractures were studied along
      subspecialty lines. Differences in patient groups, practice patterns, and
      treatment strategies based on subspecialty assignment were found. Overall
      treatment followed traditional lines, with plastic surgeons involved in all types
      of pediatric facial fractures, whereas otolaryngology and oral surgeons were more
      limited in their operative scope, despite equal call responsibilities. It is
      believed that the managed care arena is a competitive environment in which it
      will be important to know the strengths and weaknesses of the plastic surgery
      specialty, as well as those of competing specialties, as patient contracts are
      negotiated. The overlap of plastic surgery, otolaryngology, and oral surgery in
      the care of facial trauma could result in plastic surgeons being left off of
      managed care participant lists. This study highlights plastic surgeons as
      efficient deliverers of quality care for pediatric facial fractures. Although the
      treatment of these fractures has fallen into the duties shared by all three
      subspecialties, data such as those presented here should strengthen our ability
      to succeed in the evolving environment of managed care.

PMID- 9655404
TI  - Fever after craniofacial surgery in the infant under 24 months of age.
AB  - A retrospective review was undertaken of 126 consecutive craniofacial procedures
      involving a transcranial component, performed at the Children's Medical Center at
      Dallas, between 1990 and 1994. Standard postoperative axillary temperature
      measurements were recorded until discharge. Age at surgery of less than 24 months
      correlated very strongly with a postoperative temperature of greater than 38
      degrees C (r = -0.92). The incidence of postoperative fever was high in all age
      groups, yet there was still a significant difference between the group younger
      than 2 years and the group in which surgery was performed after the age of 2
      years across all postoperative temperature ranges, from >38 degrees C to >39.5
      degrees C (p < 0.001, chi-square test). The white blood cell count was elevated
      above the age-related normal in 67 percent of febrile patients. There was no
      correlation between type or duration of surgical procedure, length of intensive
      care or hospital stay, or the need for blood transfusion and the development of a
      significant postoperative fever. There were minor infectious complications in
      four patients (3 percent), only one of which was a wound problem related to the
      surgery. All infectious complications were easily identifiable clinically. There
      was no mortality or serious infections. The development of postoperative fever,
      and an elevated white blood cell count, is to be expected in pediatric patients
      undergoing craniofacial procedures. The routine laboratory investigation of
      postoperative fever in pediatric craniofacial patients under 2 years of age
      without procedures involving transgression of the paranasal sinuses is not
      warranted unless there are associated clinical indicators.

PMID- 9655405
TI  - Comparative study of inferior alveolar disturbance restoration after sagittal
      split osteotomy by means of bicortical versus monocortical osteosynthesis.
AB  - The comparative study of neurosensory disturbance of the inferior alveolar nerve
      after bilateral sagittal split osteotomies was carried out. The 112 patients who
      underwent bilateral sagittal split osteotomies were divided into two groups: one
      group consisted of 62 patients (124 osteotomy sites) who received bicortical
      osteosynthesis using the lag screw principle (bicortical fixation group), and the
      other group consisted of 52 patients (104 osteotomy sites) who underwent
      monocortical osteosynthesis using miniplates (monocortical fixation group). The
      incidence of neurosensory disturbance of the inferior alveolar nerve as well as
      its recovery course was compared by patients' interview and Semmes-Weinstein
      pressure esthesiometer. Mean follow-up period was 12 months (minimum 3 months,
      maximum 36 months). The incidences of sensory disturbance of both groups were not
      significantly different at 2 weeks postoperatively. During the period 6 to 12
      months postoperatively, the number of patients having light touch sensory
      disturbance was significantly less in the monocortical fixation group than in the
      bicortical fixation group. Moreover, the number of patients complaining of
      numbness during 6 to 18 months postoperatively was significantly less in the
      monocortical fixation group. These findings suggested that the monocortical
      osteosynthesis had less damage on the inferior alveolar nerve, leading to the
      better restoration of neurosensory disturbance in patients in whom the nerve
      damage was moderate.

PMID- 9655406
TI  - Assessment of clinical outcome after flashlamp pumped pulsed dye laser treatment
      of portwine stains: a comprehensive questionnaire.
AB  - A generally accepted method to assess the clinical outcome of laser treatment of
      portwine stains is not available. This paper describes the development and
      evaluation of a comprehensive questionnaire for the assessment of the following
      portwine stain characteristics: color (hue and lightness), sharpness of boundary,
      pigmentation, size, shape, skin surface-structure, and hypertrophy of underlying
      tissue. The questionnaire was applied to photographs of 70 patients with
      previously untreated portwine stains in the head/neck area. Photographs were
      taken before treatment and after five treatments of the entire portwine stain
      with a flashlamp pumped pulsed dye laser. Each photograph was evaluated
      separately by a panel of five professionals: the treating physician, two plastic
      surgeons, a dermatologist, and a clinical photographer. Treatment results were
      assessed by comparing ratings before and after treatment. Agreement among raters
      was acceptable for all portwine stain characteristics, as was shown by weighted
      kappa analysis. The reliability of the answers was further improved by taking the
      average rating of the five panel members. The scores thus obtained were very
      reliable, with Cronbach alpha coefficients of 0.8 on average. After five
      treatments of the entire portwine stain, the most considerable changes were
      measured in the ratings for color (lightening of the stain by 33 percent),
      boundary (sharpness reduced by 38 percent), and size (13-percent decrease). Using
      the questionnaire can be helpful in the design of comparative clinical trials on
      portwine stain treatment and may facilitate comparison of treatment results
      between different treatment centers and/or different lasers.

PMID- 9655407
TI  - Skin-sparing mastectomy and immediate reconstruction: oncologic risks and
      aesthetic results in patients with early-stage breast cancer.
AB  - Skin-sparing mastectomy has been advocated as an oncologically safe approach for
      the management of patients with early-stage breast cancer that minimizes
      deformity and improves cosmesis through preservation of the skin envelope of the
      breast. Because chest wall skin is the most frequent site of local failure after
      mastectomy, concerns have been raised that inadequate skin excision could result
      in an increased risk of local recurrence. Precise borders of the skin resection
      have not been well established, and long-term local recurrence rates after skin
      sparing mastectomy are not known. The purpose of this study was to evaluate the
      oncologic safety and aesthetic results for skin-sparing mastectomy and immediate
      breast reconstruction with a latissimus dorsi myocutaneous flap and saline breast
      prosthesis. Fifty-one patients with early-stage breast cancer (26 with ductal
      carcinoma in situ and 25 with invasive carcinoma) undergoing primary mastectomy
      and immediate reconstruction with a latissimus flap were studied from 1991
      through 1994. For 32 consecutive patients, skin-sparing mastectomy was defined as
      a 5-mm margin of skin designed around the border of the nipple-areolar complex.
      After the mastectomy, biopsies were obtained from the remaining native skin flap
      edges. Patients were followed for 44.8 months. Histologic examination of 114
      native skin flap biopsy specimens failed to demonstrate breast ducts in the
      dermis of any of the 32 consecutive patients studied. One of 26 patients with
      ductal carcinoma in situ had metastases to the skin of the lateral chest wall and
      back. Four other patients, one with stage I disease and three with stage II-B
      disease, had recurrent breast carcinoma. The stage I patient had a local
      recurrence in the subcutaneous tissues near the mastectomy specimen. Two patients
      suffered axillary relapse, and one had distant metastases to the spine. The
      findings of this study support the technique of skin-sparing mastectomy as an
      oncologically safe one, based on an absence of breast ductal epithelium at the
      margins of the native skin flaps and a local recurrence rate of 2 percent after
      45 months of follow-up. Although these results need to be confirmed with greater
      numbers of patients and longer follow-up, skin-sparing mastectomy and immediate
      breast reconstruction may be considered an excellent alternative treatment to
      breast conservation for patients with ductal carcinoma in situ and early-stage
      invasive breast cancer.

PMID- 9655408
TI  - Aesthetic refinement in breast reconstruction: complete skin-sparing mastectomy
      with autogenous tissue transfer.
AB  - Aesthetic results in breast reconstruction are often compromised either by
      prominent scars or by the presence of an island of skin that differs in color and
      texture from the native breast skin. Complete skin-sparing mastectomy is a
      technique by which breast scars can be largely eliminated and the need for a
      visible skin island avoided. A circumareolar incision is used for mastectomy with
      a separate axillary incision if needed. Autogenous tissue is used to fill the
      skin envelope, and a disk of skin temporarily replaces the areola. Twenty-eight
      patients treated by this method were reviewed retrospectively. Prerequisites
      included a favorable biopsy scar location and a suitable tissue donor site. The
      mean patient age was 42.5 years, and the majority were reconstructed with TRAM
      flaps (92 percent). There was no evidence of increased morbidity or any instance
      of local recurrence during a follow-up period, which averaged 25.7 months.
      Aesthetic results were judged excellent in 12 patients, good in 11 patients, and
      fair in 5 patients. Insufficient tissue volume, shape asymmetry, and areolar
      position asymmetry were the most common factors that detracted from the quality
      of the results. Advantages of this method, besides the prospect of an ideal
      aesthetic result, include easier flap insetting and simplified subsequent
      revision procedures. Disadvantages include the requirement of a skilled ablative
      surgeon and incompatibility with conventional expander/implant methods of
      reconstruction.

PMID- 9655409
TI  - Efficient in vitro model for immunotoxicologic assessment of mammary silicone
      implants.
AB  - In clinical and experimental studies, silicone gel has been assumed to cause
      immune alterations that may be related to macrophage activation of silicone
      implants. However, it has not been proven that the immunotoxicities are caused by
      the direct contact of macrophages and silicone gel because there has not been an
      adequate experimental model. In the present study, silicone gel was loaded
      directly onto Petri dishes and was distributed uniformly to the bottom by
      centrifugation. Peritoneal macrophages and splenic lymphocytes were cultured
      either on the silicone-coated plates or on the conventional, normal plates, and
      their functions were compared with each other. The experiments were repeated
      three times. The cytotoxic activities of peritoneal macrophages on cancer cells
      were markedly augmented by cultivation on silicone gel, and the primary T
      dependent immunoglobulin M response in which macrophages participated as antigen
      presenting cells was also enhanced by incubation on silicone gel. However,
      macrophage-unrelated functions mediated by B and T lymphocytes were not affected
      by the silicone gel treatment. It was proven that the direct contact of
      macrophages with silicone gel was a primary cause of acute immune activation that
      was related to foreign body reaction. In addition, the present in vitro model
      exhibited similar silicone-induced immunotoxicities in previous animal and
      clinical studies.

PMID- 9655410
TI  - The survival of human skin stored by refrigeration at 4 degrees C in McCoy's 5A
      medium: does oxygenation of the medium improve storage time?
AB  - To establish the viable storage time of human skin stored by refrigeration at 4
      degrees C in McCoy's 5A medium and to establish whether oxygenating the medium
      improves the viable storage time, the following experiment was conducted. Eighty
      discs of human split-thickness skin graft, each 3 mm in diameter, were stored in
      40 sterile sealable containers under four different conditions: in 0.9% saline,
      in McCoy's 5A medium, in oxygenated McCoy's 5A medium, and in carbon dioxide
      supplemented McCoy's 5A medium. Skin graft viability was assessed using tissue
      culture. Skin stored in saline was viable for only 1 week, whereas skin stored in
      McCoy's 5A medium and in oxygenated McCoy's 5A medium was viable for 4 weeks.
      Skin stored in carbon dioxide supplemented McCoy's 5A solution did not even
      survive the first week. These findings show that McCoy's 5A medium allows at
      least 4 weeks of viable human skin storage by refrigeration at 4 degrees C.
      Furthermore, oxygenating the medium does not seem to improve the viable storage
      time, and carbon dioxide supplementation is detrimental. The advantages of skin
      storage by refrigeration and the implications of the above findings are
      discussed. A clinical case in which split-thickness skin was stored for
      approximately 5 weeks and still resulted in good graft take is quoted as an
      example of our experience with the use of McCoy's 5A medium.

PMID- 9655411
TI  - Electrically stimulated free-flap graciloplasty for urinary sphincter
      reconstruction: a new surgical procedure.
AB  - In electrically stimulated (dynamic) graciloplasty for urinary incontinence, the
      gracilis muscle is transposed into the pelvis, and the distal part is used to
      reconstruct a neosphincter. Clinical outcomes using this technique have been
      disappointing due to stricture of the urethra caused by ischemia in the distal
      part of the gracilis and limited gracilis length available for neosphincter
      construction. Furthermore, the urethra is twisted by the contracting gracilis,
      rather than circumferentially squeezed. The purpose of the present study was to
      test the anatomical and functional feasibility of a new surgical approach to
      reconstruct a urinary sphincter, using the gracilis muscle as a free flap. In 12
      human cadavers, the anatomical feasibility for creating a neosphincter by using
      the gracilis free flap was determined. In all cases, transfer of the gracilis
      muscle into the pelvis as a free flap (with the nerve intact) was feasible, and
      ample muscle was available to construct a neosphincter around the bladder neck.
      Gracilis neosphincter function was studied in seven dogs. The left gracilis
      muscle was subjected to transfer into the pelvis as an innervated free flap to
      create a neosphincter around the urethra. The right (control) gracilis muscle was
      lifted as a single pedicle flap, remained in situ, and was wrapped around a stent
      to mimic the urethra. Function (expressed as peak pressure generation and fatigue
      rate) and surface perfusion were determined for all gracilis muscles. In each
      dog, both sides were compared using the paired Student's t test for statistical
      analysis, and no significant difference was measured for the two groups. In
      conclusion, an innervated gracilis free flap can be used to create a neosphincter
      around the bladder neck. In an acute study in dogs, function and perfusion of the
      innervated gracilis free flap are not compromised.

PMID- 9655412
TI  - Distraction osteogenesis in the hand.
AB  - Distraction osteogenesis was used to correct congenital hand deformities in 12
      digits. The patients' ages at the time of distraction ranged between 2.5 and 7
      years. A total of nine patients underwent lengthening of 12 bones. The average
      period of distraction was 31.1 +/- 17.6 days. The average length of distraction
      was 23.6 +/- 7.3 mm. Seventeen percent of the patients after lengthening had an
      angular deformity that required remodeling of the regenerate. No infections were
      noted. Distraction osteogenesis provides a useful tool for reliable and
      predictable correction of osseous defects with vascular bone in patients with
      congenital anomalies of the hand.

PMID- 9655413
TI  - "Spaghetti wrist": management and results.
AB  - A retrospective review of 60 patients with "spaghetti wrist" lacerations operated
      on by the authors between July of 1988 and June of 1996 was completed. Spaghetti
      wrist injuries were defined as those occurring between the distal wrist crease
      and the flexor musculotendinous junctions involving at least three completely
      transected structures, including at least one nerve and often a vessel. A total
      of 41 men and 19 women, average age of 29.0 years (range, 5 to 54 years),
      sustained spaghetti wrist injuries. The most frequent mechanisms of injury were
      accidental glass lacerations (61.0 percent), knife wounds (23.7 percent), and
      suicide attempts (8.5 percent). An average of 7.8 structures were injured
      including 5.8 tendons, 1.2 nerves, and 0.73 arteries. The most frequently injured
      structures were flexor carpi ulnaris (66.7 percent), median nerve (60.0 percent),
      flexor digitorum superficialis 2-5 (59.2 percent), ulnar nerve (58.3 percent),
      and ulnar artery (56.7 percent). A predilection for injury to the ulnar
      structures was observed. The flexor carpi ulnaris was more commonly injured than
      the more superficial central and radial palmaris longus (48.3 percent) and flexor
      carpi radialis (45.0 percent). The most common pattern of injury involved the
      ulnar nerve and artery and flexor carpi ulnaris, or so-called ulnar triad (41.7
      percent). Combined median nerve, flexor carpi radialis, and palmaris longus
      lacerations occurred in 26.7 percent. Simultaneous lacerations of both median and
      ulnar nerves occurred in 23.3 percent. No distinct pattern of injury was noted in
      patients with simultaneous injury to both nerves. Simultaneous lacerations of
      both ulnar and radial arteries occurred in 6.7 percent; neither artery was
      injured in 33.3 percent. In the subset of 19 patients available for follow-up
      examination, range of motion was excellent in 12 patients and good in 7 patients.
      In 12 patients with sufficient follow-up, intrinsic muscle recovery was good in 7
      patients and fair to poor in 5 patients. Sensory return was disappointing: seven
      patients recovered only protective sensation and five patients demonstrated
      return of two-point discrimination that ranged from 7 to 12 mm in three patients
      and from 2 to 6 mm in two patients.

PMID- 9655414
TI  - Extensor digitorum brevis muscle flap: new refinements.
AB  - Two original operative techniques of raising the extensor digitorum brevis muscle
      flap are presented. These methods allow for covering distal foot defects that are
      difficult to cover by other reconstructive means. In the first technique, the
      flap is based on an extended distal pedicle supplied by the dorsal interosseous
      artery of the first intermetatarsal space. In the second technique, the flap
      receives its vascular supply from the medial tarsal artery; this procedure may be
      valuable when the vascular supply of the dorsalis pedis pedicle has been
      disrupted. To confirm the availability of these vascular pedicles, cadaver
      dissections were performed and proved that the extended pedicle dissection
      enhances the rotation arc of the flap. Four selective clinical cases, in which
      the flap was successfully used, are discussed. Advantages of these techniques, in
      reconstructing large defects in the distal foot, are delineated.

PMID- 9655415
TI  - Limb-salvage in reconstruction of recalcitrant pressure sores using the
      inferiorly based rectus abdominis myocutaneous flap.
AB  - Pressure sore closure is frequently a reconstructive challenge. This challenge is
      particularly evident in cases of multiply recurrent sores. In such settings,
      there are often opportunities to manage the recurrent wounds either by repeated
      advancement of previous flaps or by design of alternative ones. However, these
      interventions are not always feasible, and limb amputation with total thigh flap
      closure must be considered. A review of operative experience with seven such
      complex pressure sores in seven patients is presented. Each patient had
      previously suffered a permanent thoracic-level spinal cord injury. Prior attempts
      at wound closure were unsuccessful. Despite consideration of all described
      locoregional flaps, no limb-sparing procedure could be designed satisfactorily.
      As an alternative to either hip disarticulation and total thigh flap coverage or
      distant free-tissue transfer, we reconstructed the debrided ulcer beds with
      inferiorly based rectus abdominis myocutaneous flaps. Six of the seven wounds
      healed primarily, whereas one required repeated debridement and the addition of a
      gracilis muscle flap to achieve complete closure. Postoperative follow-up has
      ranged from 6 to 45 months. Each patient has returned to his baseline
      preoperative activity level with no clinical compromise of abdominal wall
      function. All wounds have healed. Successful application of the inferiorly based
      vertical rectus abdominis myocutaneous flap for cases of both recalcitrant
      ischial and trochanteric pressure sores is demonstrated and its consideration is
      advocated if no reconstructive options short of extremity amputation and total
      thigh flap coverage exist for such challenging sores.

PMID- 9655416
TI  - Determination of endogenous growth factors in human wound fluid: temporal
      presence and profiles of secretion.
AB  - Growth factors are important substances in the central control of wound healing
      during the exudative phase. Although these peptides have been applied frequently
      to chronic wounds in clinical studies, little is known about the naturally
      occurring levels at the wound site in correlation to healing in superficial
      wounds. We have therefore investigated the presence of these cytokines in partial
      thickness wounds. In 16 patients undergoing reconstructive surgery, split
      thickness skin wounds were enclosed in cutaneous vinyl chambers filled with 2.5
      ml of saline. Chambers placed over unwounded skin served as controls. After 24
      hours, the accumulated wound fluid was harvested and replaced by 2.5 ml of saline
      until the wounds were healed. Wound fluid was centrifuged, aliquoted, and frozen
      at -70 degrees C. Samples were analyzed for protein and growth factors (insulin
      like growth factor-1, epidermal growth factor, basic fibroblast growth factor,
      platelet-derived growth factor-AB, interleukin-1alpha, and transforming growth
      factor-beta1 and -beta2) and insulin-like growth factor-binding proteins 1 and 3
      using a monoclonal Sandwich enzyme-linked immunosorbent assay and
      radioimmunoassay. All wounds healed in the liquid environment within 7 days
      (macroscopically) and 11 days (barrier function), respectively. In wound fluid,
      protein concentrations dropped from 5 mg/ml on day 1 to a baseline of 0.1 mg
      (unwounded skin), indicating a return of the barrier function. All growth factors
      could be measured already after 24 hours postwounding. However, the
      concentrations measured varied from 10 to more than 10,000 pg/ml between the
      different factors. The highest range was found for insulin-like growth factor-1
      (21,000 to 41,000 pg/ml), the lowest for epidermal growth factor (3 to 63 and 3
      to 88 pg/ml, respectively). Two different patterns of kinetics were
      distinguished: (1) a high initial peak decreasing to baseline values or below
      serum levels by the time of healing (insulin-like growth factor-1, insulin-like
      growth factor binding protein-1, -3, basic fibroblast growth factor, epidermal
      growth factor, platelet-derived growth factor-AB, transforming growth factor
      beta1) and (2) a low initial concentration followed by an increase to a maximum
      at the time of epithelialization (interleukin-1alpha, transforming growth factor
      beta2). Comparing the growth factor levels measured to serum baseline values, it
      was found that four of the growth factors appeared in wound fluid at above serum
      concentrations (interleukin-1alpha, transforming growth factor-beta2, basic
      fibroblast growth factor, epidermal growth factor); the other factors never
      reached serum values in wound fluid (insulin-like growth factor, transforming
      growth factor-beta1, platelet-derived growth factor-AB). It is concluded that the
      different profiles of secretion might reflect different functions of polypeptide
      growth factors such as stimulation of epithelialization (epidermal growth factor,
      insulin-like growth factor-1), matrix synthesis (transforming growth factor
      beta), and inflammatory stimulation (interleukin-1alpha). The concentrations
      determined could serve as guidelines for adapted administration of growth factors
      once correlations to healing disorders such as overhealing and ulceration are
      established.

PMID- 9655417
TI  - Human wound contraction: collagen organization, fibroblasts, and myofibroblasts.
AB  - The closure of ungrafted sacrococcygeal pilonidal sinus excisional wounds was
      studied in 15 patients. Wound punch biopsies were taken on a regular basis, and
      histologic sections were made. To document changes, computer-assisted
      morphometric image analysis was employed. Initial average wound depth was 37.8 +/
      4.6 mm, and complete closure (0 wound depth) was reached by 68 days. Wound
      contraction contributed 88 percent to wound closure, whereas the deposition of
      scar only contributed 12 percent. Maximum cells density within granulation tissue
      was reached by day 18. Myofibroblasts, identified by alpha-smooth muscle actin
      immunostaining, first appeared on day 11. Unlike those observed in laboratory
      animals, myofibroblasts were a minor cell population of granulation tissue, never
      exceeding 10 percent of the cells. The pattern of collagen fiber organization was
      documented by polarized light microscopy of Sirius red-stained sections. Early
      granulation tissue collagen fibers demonstrated a fine greenish birefringence,
      whereas more mature granulation tissue collagen fibers were thicker, displaying
      orange-yellowish birefringence. Myofibroblasts were associated exclusively with
      thicker collagen fibers, whereas fibroblasts were associated with both fine and
      thick collagen fibers. It is proposed that human wound contraction involves a
      volume change whereby normal dermal and adipose tissues are pulled into the
      defect by forces generated within fibroblasts.

PMID- 9655418
TI  - Epidermal regulation of dermal fibroblast activity.
AB  - Although the association between delayed burn wound healing and subsequent
      hypertrophic scar formation is well-established, the mechanism for this
      relationship is unknown. Unhealed burn wounds lack an epidermis, suggesting a
      possible regulatory role for the epidermis in controlling dermal fibroblast
      matrix synthesis. Therefore, we examined the effect of epidermal cells and media
      conditioned by epidermal cells on fibroblast collagen synthesis and replication.
      Purified fibroblast and keratinocyte cell strains were developed from discarded
      normal adult human skin. Conditioned media were created by incubation of cytokine
      free and serum-free medium with either confluent fibroblast or keratinocyte
      cultures for 18 hours (n = 3). Nearly confluent fibroblast cultures were exposed
      for 48 hours to graded concentrations of either unconditioned medium (control),
      conditioned medium, or varying numbers of keratinocytes. Replication was
      quantified by the incorporation of 3H-thymidine. Collagen synthesis was measured
      by the incorporation of 3H-proline into collagenase-sensitive protein. Data were
      compared using analysis of variance (ANOVA) and linear regression. Keratinocyte
      conditioned medium induced a significant increase in replication (n = 3) (p =
      0.004) and a decrease in collagen synthesis (n = 6) (p < 0.001). In contrast,
      neither fibroblast conditioned medium nor control medium had an effect on
      fibroblast replication or collagen synthesis. Co-culture of fibroblast with a
      graded number of keratinocytes similarly decreased collagen synthesis (n = 6) (p
      < 0.001). Dermal fibroblast collagen synthesis appears to be regulated by a
      soluble keratinocyte product. This result suggests a mechanism for the clinical
      observation that unhealed burn wounds, which lack the epidermis, demonstrate
      excess collagen production and scar. Clinical strategies to decrease hypertrophic
      scar should include an attempt at early wound closure with skin grafting or the
      application of cultured epithelial autografts.

PMID- 9655419
TI  - Ischemic preconditioning improves the survival of skin and myocutaneous flaps in
      a rat model.
AB  - Inadequate blood supply of pedicle flaps results in partial necrosis, and
      prolonged ischemia during free-tissue transfer can result in partial or complete
      flap necrosis. Recent research in the field of cardiovascular surgery has shown
      that ischemic preconditioning (repeated brief episodes of coronary artery
      occlusion followed by reperfusion) improves myocardial muscle survival when the
      heart is subsequently subjected to prolonged ischemia. Preconditioning of skin or
      myocutaneous flaps as either pedicle or free flap models has never been studied.
      The goal of this investigation was to measure the effect of ischemic
      preconditioning on myocutaneous and skin flap survival areas and total necrosis
      rates after variable periods of global ischemia. In 220 rats, 100 transverse
      rectus abdominis myocutaneous flaps and 120 dorsal cutaneous flaps were
      randomized into treatment and control groups. The treatment flaps underwent
      preconditioning by three cycles of 10 minutes of pedicle clamping followed by 10
      minutes of reperfusion for a total preconditioning period of 1 hour. The control
      flaps were perfused without clamping for 1 hour. Both control and treatment flaps
      then underwent global ischemia for 0, 2, 4, 6, 10, or 14 hours by pedicle
      clamping. Flap survival area was measured on the fifth postoperative day.
      Statistical analysis was performed with analysis of variance, student's t tests,
      and probit analysis. Preconditioning improved survival areas of pedicle
      myocutaneous flaps (0-hour group) from 47 +/- 16 percent (mean percent area
      surviving +/- SD) to 63 +/- 5 percent. This difference was statistically
      significant (t test, p < 0.04). There was no statistically significant
      improvement in pedicle skin flap survival. For free flap models (flaps undergoing
      global ischemia), preconditioning increased the survival areas of skin and
      myocutaneous flaps (analysis of variance, p < 10(-5)). For the skin flap model,
      statistical significance of the survival area difference was reached at 6, 10,
      and 14 hours of ischemia (t test, p < 10(-4)). The magnitude of this effect was
      higher in the myocutaneous flap model and reached statistical significance at 2,
      4, 6, and 10 hours of ischemia (p < 10(-3)). Preconditioned flap survival areas
      were increased by two to five times that of non-preconditioned flaps at these
      ischemia times. Preconditioning lowered total necrosis rates at all ischemia
      times for both flap models. The critical ischemia time when 50 percent of skin
      flaps became totally necrotic (CIT50) improved from 6.9 to 12.4 hours by
      preconditioning. Similarly, preconditioning improved the CIT50 of myocutaneous
      flaps from 3.6 to 9.2 hours. For the first time, statistically significant
      improvements of partial necrosis areas and total necrosis rates have been
      demonstrated through intraoperative ischemic preconditioning of skin and
      myocutaneous flaps. In clinical practice, application of this technique may lead
      to improved survival during pedicled or free transfer of myocutaneous flaps and
      free transfer of skin flaps.

PMID- 9655420
TI  - Involvement of neutrophils in ischemia-reperfusion injury of inguinal island skin
      flaps in rats.
AB  - Increased production of oxygen free radicals and infiltration of neutrophils into
      tissue subjected to ischemia-reperfusion have emphasized that neutrophils play a
      direct role in the development of injury. The present study was designed to
      elucidate the effect of FK506, a new immunosuppressive drug, on 11 hours of
      complete ischemia and reperfusion of the inguinal island skin flaps in rats.
      Group 1 (n = 10) control animals underwent ischemia and reperfusion and no
      treatment. Group 2 (n = 10) animals received FK 506 0.3 mg/kg/day, and group 3 (n
      = 9) animals received 0.5 mg/kg/day intramuscularly for 3 days before the
      ischemia. The effect of the drug was evaluated by measuring flap survival and
      tissue malondialdehyde content and myeloperoxidase activity and also by
      histopathologic examination of the skin specimens taken at the 1st and 24th hour
      after reperfusion. The survival of flaps controlled for 7 days was found to be
      significantly improved in group 2 (65.0 +/- 10.93 percent) and group 3 (93 +/-
      6.25 percent) when compared with the control group (14 +/- 10.12 percent) (p <
      0.04 and p < 0.0001). The tissue contents of malondialdehyde and activities of
      myeloperoxidase were significantly lower in groups 2 and 3 than in the control
      group. Three days of pretreatment with FK506 significantly reduced neutrophil
      infiltration in groups treated with either of the doses. These results showed
      that neutrophils play an important role in island flap survival associated with
      ischemia-reperfusion injury. Increased neutrophil infiltration was found related
      with increased levels of malondialdehyde and myeloperoxidase. Flap necrosis and
      the increase in malondialdehyde, myeloperoxidase, and neutrophil infiltration
      were improved by FK506 pretreatment, a neutrophil modulating agent.

PMID- 9655421
TI  - Cell transplantation from limb allografts.
AB  - A murine model of skeletal tissue transplantation was developed to study the
      allograft rejection process in mice for limb allograft transplantation. Muscle,
      bone, and skin have been shown to be strong antigenic stimuli in vascularized
      allograft models, and cells from these sources were used for transplantation.
      Using enzymatic digestion, keratinocytes, myocytes, and osteocytes were harvested
      from B10.A mice tissues, dissociated into single cells, and then grown in culture
      for 14 to 21 days. Each cell type was marked with an intracellular fluorescent
      marker before transplantation of the cells into pockets in the rectus abdominis
      muscle of a syngenic host. All cell types remained viable and were detectable 2
      weeks following transplantation when examined histologically and observed under a
      fluorescent microscope. Transplanted osteocytes were found to produce bone 8
      weeks following transplantation. These results demonstrate that individual cells
      transplanted into muscle pockets survive and have the ability to produce
      extracellular matrix in this mouse model of skeletal tissue transplantation. Use
      of this model will allow transplantation of the cellular components comprising
      limb allografts to study the relative antigenicities and the rejection of the
      separate cells with the advanced immunologic techniques available for mice. A
      better understanding of immunologic responses to these individual tissue
      components may enable specific donor tissue or host immune modification to
      achieve skeletal tissue transplantation without immunosuppression. These findings
      are particularly valuable to the field of tissue engineering where allogeneic
      cells may be used in cell/polymer constructs for reconstructive procedures.

PMID- 9655422
TI  - Replantation of amputated nose by microvascular anastomosis.

PMID- 9655423
TI  - Modified chondrocutaneous advancement flap for ear reconstruction.

PMID- 9655424
TI  - Endoscopically assisted suspension in facial palsy.

PMID- 9655425
TI  - Conversion from tridimensional surface to a plane for measuring expanded skin
      area with computer aid.

PMID- 9655426
TI  - The pedicled tensor fasciae latae flap as a salvage procedure for an infected
      abdominal mesh.

PMID- 9655427
TI  - Simultaneous rhytidoplasty and lipoinjection: a comprehensive aesthetic surgical
      strategy.
AB  - Fat autografting is an accepted technique in the treatment of depressions or
      augmenting thin soft tissues. Aging soft tissues become thin, among them the
      subcutaneous fat layer, muscles, and fasciae, and these tissues in addition
      become flaccid. Therefore, to get better results in rejuvenation plastic surgery,
      a good alternative is the combination of lifting the flaccid tissues and
      thickening the thin soft tissues with a lack of contour and definition, which
      enhances the aspect of the entire face and neck. For 10 years in our practice, we
      have been combining rhytidoplasty (which includes systematizing superficial
      musculoaponeurotic system and platysma plication) with lipoinjection, placing
      thin rolls of autologous fat into the facial and cervical muscles, or at least
      under the fasciae. The results reveal a very high success rate with few minor
      complications. Proper diagnosis, patient selection, and adequate surgical
      technique produce predictable and favorable aesthetic results. A concurrent
      retrospective study of 357 consecutive patients who underwent simultaneous
      rhytidoplasty and lipoinjection was conducted over a 10-year period (1985 to
      1995). The purpose of this article is to show our experience with this method,
      including long follow-up observations.

PMID- 9655428
TI  - Numerical modeling of facial aging.
AB  - Facial aging is a biological phenomenon. Skin properties change with time, and
      gravity and facial expressions exert mechanical deformation. Knowledge of these
      alterations may suggest ways to reverse them by identifying the corresponding
      distortional forces. The aim of this study was to determine a pattern of change
      for parameters of the face during the aging process, based on the numerical
      fitting of measures from a sample of patients. The first aspect of this study was
      to define adequate facial parameters and means of measuring them. Subsequently,
      each parameter was defined individually, and these data were analyzed as a set.
      The sample for the research was restricted to a group of 40 white female patients
      with a history of limited exposure to the sun, with ages ranging from 25 to 65.
      The reason for choosing this sample was the availability of frontal pattern
      photographs at different ages. The parameters for each patient were measured at
      two different ages. A strong correlation was found between age and behavior of
      the parameters. This aging model can be verified qualitatively by comparing
      photographs of a patient with manipulated photographs simulating aging. The
      quantitative verification of the model was done through the comparison of the
      measured and the predicted parameters.

PMID- 9655429
TI  - Relative maxillary retrusion as a natural consequence of aging: combining
      skeletal and soft-tissue changes into an integrated model of midfacial aging.
AB  - The contribution of maxillary retrusion to the formation of the nasolabial fold
      is evaluated in the present study. Clinical observation of patients from the
      craniofacial unit with concomitant maxillary retrusion revealed prominent signs
      of midfacial aging: specifically these individuals displayed a prominent
      nasolabial fold at an early age. This observation led to the hypothesis that
      relative maxillary retrusion occurs as a normal feature of the aging process.
      Retrusion of the lower facial skeleton below the soft tissue of the nasolabial
      fold causes the nasolabial fold to appear more prominent. To test this
      hypothesis, computed tomographic data were assembled retrospectively and included
      both males and females, young and old. The age range of the males (n = 14) was 18
      to 24 years (young) and 43 to 57 years (old); the age range of the females (n =
      14) was 15 to 30 years (young) and 43 to 57 years (old). All individuals had
      complete upper dentition and had no bony facial injury. Computed tomographic data
      were reconstructed into three-dimensional images, and a technique was developed
      to create a standardized lateral view which eliminated rotational variance.
      Analysis of anterior-posterior changes showed that there is a tendency for the
      lower maxillary skeleton at pyriform to become retrusive with age relative to the
      upper face in individuals with complete dentition. Findings were very significant
      for both males and females (p = 0.0001 and p = 0.002, respectively). In both
      groups, a slight increase in vertical maxillary dimension was noted, consistent
      with previous studies. It is suggested that relative maxillary retrusion is a
      factor in the development of the nasolabial fold. The skeletal features of normal
      midfacial aging can be combined with the soft-tissue features such as ptosis and
      atrophy into an integrated model of midfacial aging. A model such as this has
      significance regarding both the timing and choice of procedure used to restore
      the aging midface.

PMID- 9655430
TI  - The tissue effects of ultrasound-assisted lipoplasty.
AB  - The objective of our study was to investigate the effects of ultrasonic energy on
      tissues, using a porcine model, performed under various instrumental and
      procedural parameters. Domestic pigs were anesthetized and prepared for surgery.
      An incision was made on the side of the hip randomly assigned to the right or
      left side. Tumescence solution was infiltrated via a blunt tip, small diameter
      cannula, followed by performance of standard liposuction. On the contralateral
      side, a similar incision was made. For ultrasonic liposuction experiments without
      the sheath, a percutaneous introducer was inserted into the incision, which was
      protected at the entry site from contact with the cannula. Tumescence solution
      was infiltrated via a blunt tip, small diameter cannula, and then the site was
      treated with ultrasonic energy at maximum output from the machine with
      liposuction concurrent through the hollow cannula. The experiments with the
      sheath did not require a pretreatment with tumescence solution but consisted of
      tumescence solution pumped through the sheath at a low infusion rate, with
      concurrent treatment utilizing ultrasonically assisted liposuction through the
      central lumen of the cannula. In all cases, the lipoaspirate was preserved for
      biochemical analysis. After treatment, the pigs were euthanized, and samples for
      histopathology were taken. The pigs were then perfused with a radio-opaque
      solution through the left ventricle following preperfusion with saline. The
      groups were ultrasound-assisted liposuction with sheath (n = 3), ultrasound
      assisted without sheath (n = 4), and tumescence alone (n = 1), with standard
      liposuction performed on the contralateral side for all ultrasound-assisted
      liposuction animals. The lipoaspirates from the ultrasonically assisted
      liposuction with the sheath showed significantly less blood loss (measured as
      hemoglobin in the aspirate) than standard liposuction (p = 0.012) at comparable
      levels of fat (measured as triglycerides in the aspirate). The lipoaspirates from
      ultrasound-assisted liposuction without the sheath showed blood loss comparable
      to that experienced with standard liposuction. The ratio of hemoglobin to
      triglyceride was lowest in the ultrasound-assisted group with (p = 0.01) and
      without (p = 0.06) the sheath when compared to traditional liposuction. In both
      of these treated groups, the radiograms of the perfused areas showed
      significantly less vascular disruption when compared with suction-assisted
      liposuction. Histopathologic examination of specimens taken from various treated
      areas showed substantial tissue damage comparable in ultrasound- and suction
      assisted liposuction treated groups. This preliminary experimental study showed
      that ultrasound-assisted lipoplasty is comparable to traditional suction-assisted
      lipoplasty. Treatment with ultrasound provided more significant
      hemoglobin/triglyceride ratios, indicative of more lipid aspirated per hemoglobin
      lost, and better preservation of vascular tissues as demonstrated by our
      perfusion studies. Treatment with the sheath showed a significantly lower
      hemoglobin release with a diminished volume infused into the subcutaneous space
      during the procedure.

PMID- 9655431
TI  - Follicular bisection in hair transplantation surgery: an in vitro model.
AB  - The aim of this study was to evaluate, in an in vitro model, the survival and
      growth rates of transversely sectioned human hair follicles to assess
      experimentally the soundness of this approach as a future possible method for
      "duplicating" available donor hair grafts in hair transplantation procedures. A
      total of 300 human anagen hair follicles was obtained from 10 healthy male
      patients. Follicles were thus randomly assigned to one of the following groups:
      group A (control; n = 100 follicles), cultured intact as dissected, and group B
      (experimental; n = 200 follicles), transversely transected, parallel to the
      epidermal surface and immediately below the bulge area, to obtain 200 lower-half
      follicles and 200 upper-half follicles. Isolated hair follicles from both groups
      were maintained in culture for 10 days. The length of each follicle was measured
      immediately following isolation and at the end of the 10-day culture period. No
      statistically significant differences were found between the growth rate of
      intact follicles (mean 10-day growth rate = 2.71 mm) and of lower-half follicles
      (mean 10-day growth-rate = 2.64 mm), whereas a statistically significant
      difference was found between the growth rate of follicles from the two above
      mentioned groups and the growth rate of the "upper-half" follicles (mean 10-day
      growth rate = 1.07 mm). Histologic analysis demonstrated that both intact and
      lower-half follicles maintained a normal histologic appearance, whereas in upper
      half follicle sections we invariably detected a region of intense cell
      proliferation, reminiscent of a regenerated follicular papilla, surrounding the
      lowermost part of the follicle. In our opinion, the reported in vitro survival
      rate of transected human hair follicles might represent an interesting starting
      point in striving to augment the number of donor hairs available during a hair
      transplantation procedure.

PMID- 9655432
TI  - Late infection of a breast prosthesis with Enterococcus avium.

PMID- 9655433
TI  - Umbilicated nipples eversion after breast augmentation.

PMID- 9655434
TI  - Acute median nerve compression associated with tumescent fluid administration.

PMID- 9655435
TI  - Calvarial fixation during endoscopic brow lift.

PMID- 9655436
TI  - Resorbable screw fixation technique for endoscopic brow and midfacial lifts.

PMID- 9655437
TI  - Simple technique to correct the bony septum.

PMID- 9655438
TI  - Breast reduction ad absurdum.

PMID- 9655439
TI  - Molecular basis for tissue expansion: clinical implications for the surgeon.
AB  - A wide variety of tissue expansion techniques have been used for breast
      reconstruction, craniofacial surgery, and burn care in plastic reconstructive
      surgery. However, the basic mechanism by which skin and surrounding tissue
      respond to mechanical expansion remains unclear. Recent studies have revealed the
      biomechanical aspects of cells subjected to strain and various factors involved
      in the stretch-induced signal transduction pathway. In this regard, we have
      reported previously that mechanical force increases keratinocyte growth and
      protein synthesis and alters cell morphology. The mechanism by which strain
      causes an enhancement of cellular growth appears to be a network of several
      integrated cascades, implicating growth factors, cytoskeleton, and the protein
      kinase family. Recently, additional evidence has accumulated that mechanical
      strain stimulates signal transduction pathways that could trigger a series of
      cascades eventually leading to a new skin production. For example, we have
      evidence suggesting a key role for protein kinase C (PKC) in mechanosignaling as
      PKC is activated and translocated in keratinocytes subjected to strain in an
      isoform-specific manner. In this report, molecular mechanisms leading to
      enhancement of skin surface area are reviewed, and possible future applications
      are discussed.

PMID- 9655440
TI  - Maxillomandibular fixation utilizing cortical bone screws.

PMID- 9655441
TI  - The box frame fixator: a technique for simultaneous fracture and free-tissue
      transfer management.

PMID- 9655442
TI  - Arteriovenous shunts.

PMID- 9655443
TI  - Primary repair of whole-shaft epispadias with cleft glans penis in a 30-year-old
      man.

PMID- 9655444
TI  - Should electrodiagnostic studies be done in patients with carpal tunnel syndrome?

PMID- 9655445
TI  - Surgical treatment of abdominal pain after mammary reconstruction by pedicled
      transverse rectus abdominis muscle (TRAM) flap.

PMID- 9655446
TI  - The best of Goldwyn collection.

PMID- 9655447
TI  - Venous drainage of the reverse-flow flap.

PMID- 9655448
TI  - Lessening the pain of suture removal.

PMID- 9655449
TI  - Alternative wound dressings.

PMID- 9655450
TI  - The Baker phenol peel formula.

PMID- 9655451
TI  - Early orthodontic therapy of cleft lip and/or palate patients.

PMID- 9655452
TI  - A new approach for the treatment of recurrent large abdominal hernias: the
      overlap approach.

PMID- 9655453
TI  - Use of polyfilament suture as a source of microsuture.

PMID- 9655454
TI  - Bleeding of silicone gel breast implants.

PMID- 9655455
TI  - Muscle flap ischemia secondary to acute arterial desaturation following
      extubation.

PMID- 9655456
TI  - Safety and efficacy report: external fatty tissue massage.

PMID- 9655457
TI  - Reconstruction of a large thoracoabdominal wall defect.

PMID- 9655458
TI  - Nevoid hyperkeratosis of the areola.

PMID- 9655459
TI  - Mammography of the postreconstruction breast.

PMID- 9655460
TI  - Postphlebitic ulcer treated by means of neurocutaneous distally based sural flap.

PMID- 9655461
TI  - The posterior interosseous cutaneous flap.

PMID- 9655462
TI  - Prenatal counseling for cleft lip and palate.

PMID- 9655463
TI  - Triangular flap for a red lip: a simple modification for cleft lip surgery.

PMID- 9655464
TI  - How are we to judge?

PMID- 9655465
TI  - Long-term possible hazardous effects of ultrasonically assisted lipoplasty.

PMID- 9655466
TI  - Ultrasonic surgical aspiration: instrumentation, clinical experience, and safety.

PMID- 9655467
TI  - Chemokine receptor expression in cultured glia and rat experimental allergic
      encephalomyelitis.
AB  - Chemokines are a group of pro-inflammatory peptides that mediate leukocyte
      migration and activation. Several members of the chemokine family have been shown
      to be synthesized by cells of the central nervous system (CNS). To begin to
      address the role of chemokine receptors in CNS physiology, we identified, by
      molecular cloning techniques, the rat orthologs of the chemokine receptors, CCR2,
      CCR3, CCR5, and CXCR4. CCR2 and CCR5 expression was detected in rat spleen, lung,
      kidney, thymus and macrophages; CCR5 mRNA was also detected in rat brain. Primary
      cultures of rat microglia expressed CCR5 mRNA that was regulated by IFN-gamma,
      while both cultured astrocytes and microglia were found to contain mRNA for CXCR4
      and CX3CR1. Induction of experimental allergic encephalomyelitis (EAE) in the rat
      was accompanied by increased levels of CCR2, CCR5, CXCR4, and CX3CR1 mRNAs in the
      lumbar spinal cords of animals displaying clinical signs of the disease. These
      data identify the rat orthologs of chemokine receptors and demonstrate that
      brain, spinal cord, and cultured glial cells express chemokine receptors that can
      be regulated both in vitro and in vivo.

PMID- 9655468
TI  - Linkage and association analysis of genes encoding cytokines and myelin proteins
      in multiple sclerosis.
AB  - Several genetic factors are likely to play a role in the etiology of multiple
      sclerosis (MS). We used a candidate gene strategy in a study of polymorphic
      markers within or close to genes encoding cytokines (interferon-gamma (IFN
      gamma), interleukin-2 (IL-2), IL-4, IL-4 receptor (IL-4R), IL-10, transforming
      growth factor-beta1 and -beta2) and myelin proteins (2',3'-cyclic-nucleotide 3'
      phosphohydrolase (CNP:ase), myelin associated glycoprotein, oligodendrocyte
      myelin glycoprotein, proteolipid protein) in 34 Swedish multiplex MS families and
      in 147 sporadic MS patients and 95 healthy controls. No evidence for linkage was
      observed in two-point linkage analysis. However, a slightly positive LOD score of
      0.88 (theta = 0.01) for IFN-gamma was found. Affected pedigree member (APM)
      analysis indicated a possible linkage with TGF-beta2 (p = 0.008) and IL-4R (p =
      0.043). None of the cytokine markers were associated with MS in case-control
      analysis. Our results suggest a possible importance of the TGF-beta2, IL-4R and
      IFN-gamma genes in MS.

PMID- 9655469
TI  - MCP-1, MCP-2 and MCP-3 expression in multiple sclerosis lesions: an
      immunohistochemical and in situ hybridization study.
AB  - Chemokines are low molecular weight chemotactic cytokines that have been shown to
      play a central role in the perivascular transmigration and accumulation of
      specific subsets of leukocytes at sites of tissue damage. Two major families have
      been defined depending on the positioning of four conserved cysteines. The CXC
      chemokines predominantly attract neutrophils, whereas the CC chemokines
      predominantly attract monocytes and other leukocyte cell types. Members of the
      monocyte chemotactic protein (MCP)-1 family form a major component of the CC
      family of chemokines and are considered the principal chemokines involved in the
      recruitment of monocytes/macrophages and activated lymphocytes. In this study we
      addressed the expression and distribution of MCP-1, -2 and -3 in multiple
      sclerosis (MS) lesions of differing ages and levels of inflammatory activity
      using immunohistochemistry and in situ hybridization. In acute and chronic-active
      MS lesions immunoreactivity for MCP-1, -2 and -3 was prominent throughout the
      lesion center with reactivity diminishing abruptly at the lesion edge.
      Hypertrophic astrocytes were strongly reactive and inflammatory cells showed
      variable reactivity. Outside of the lesion only hypertrophic astrocytes were
      reactive. The results obtained by in situ hybridization for MCP-1 were in
      agreement with those obtained by immunostaining. In more chronic lesions
      immunoreactivity for MCP-1, -2 and -3 was considerably diminished, and in chronic
      silent lesions immunoreactivity was restricted to a few scattered reactive
      astrocytes. Normal control brains showed no immunoreactivity for MCP-1, -2 and 
      3. Although the cellular distribution of all three members of this family was
      similar, antibodies to MCP-3 gave prominent staining of the extracellular matrix
      that was not noted for MCP-1 and -2. These results support the conclusion that
      members of the MCP family of chemokines are involved in the development of MS
      lesions in the central nervous system.

PMID- 9655470
TI  - Expression of accessory molecules and cytokines in acute EAE in marmoset monkeys
      (Callithrix jacchus).
AB  - Accessory molecules and cytokines are involved in the immunopathogenesis of
      multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) in
      rodent models, and are potential targets for immunotherapy. Evaluation of such
      experimental therapies requires appropriate animal models. Therefore, we analysed
      the expression of selected accessory molecules and cytokines in the brain of
      marmoset monkeys (Callithrix jacchus) with acute EAE, a newly described non-human
      primate model for MS. All animals experienced active disease clinically and
      histopathologically with strong resemblance to MS. Perivascular infiltrates of
      mononuclear cells showed abundant expression of CD40. CD40 was expressed on
      macrophages, indicating that T cell priming and macrophage effector functions may
      result from local CD40-CD40L interactions. CD40 ligand (CD40L) and B7-2 (CD86)
      were also expressed, but to a lower extent, while B7-1 (CD80) expression was
      limited. Both pro-inflammatory and anti-inflammatory cytokines were produced
      within individual lesions during active disease (IFN-alpha, IFN-gamma, TNF-alpha,
      IL-1alpha, IL-1beta, IL-2, IL-4, IL-10 and IL-12). This suggests that relative
      levels rather than sequential expression of Th1- and Th2-type cytokines determine
      disease activity. These findings demonstrate the value of EAE in marmoset monkeys
      as a model to assess the role of accessory molecules and cytokines in multiple
      sclerosis, and to evaluate targeted intervention.

PMID- 9655471
TI  - Local production of TGF beta1 inhibits cerebral edema, enhances TNF-alpha induced
      apoptosis and improves survival in a murine glioma model.
AB  - We have previously reported that local secretion of either TNF-alpha or TGF beta1
      by intracerebral SMA-560 malignant glioma tumor cells can reduce or eliminate
      tumor growth in mice. However, the use of TNF-alpha, while improving the overall
      survival of tumor bearing animals, was associated with early toxic deaths due to
      cerebral edema. In the present study, we demonstrate that TNF-alpha induces
      apoptosis of the SMA 560 cell line, as does TGF beta1, and that these two
      cytokines act in an additive fashion to enhance apoptosis and thus, to inhibit
      SMA 560 cell growth in vitro. Next, we show that the production of TGF beta1 when
      added to TNF-alpha production by central nervous system tumors in vivo abrogates
      any early deaths seen due to TNF-alpha toxicity and leads to a larger percentage
      of animals surviving CNS tumor challenge. Finally, we demonstrate that the
      production of TGF beta1 by tumor cells is associated with the abolition of tumor
      associated cerebral edema in both TNF-alpha and in non-TNF-alpha producing
      tumors. These results are important for the development of effective and less
      toxic therapies for brain tumors, as well as for examining the pathogenesis of
      tumor-related cerebral edema.

PMID- 9655472
TI  - Induction of primary immune responses by allogeneic human myoblasts: dissection
      of the cell types required for proliferation, IFNgamma secretion and
      cytotoxicity.
AB  - Non-professional antigen-presenting cells (APC) have a limited ability to
      activate T lymphocytes during normal and auto-immune responses. Myoblasts could
      play an important role as APC in the etiology of autoimmune myasthenia gravis and
      polymyositis, as well as during muscle graft rejection. We examined the role of
      different component cell subsets in the response of human peripheral blood
      mononuclear cells (PBMC) to allogeneic myoblasts. Treatment of myoblasts with
      TNFalpha or IFNgamma led to the expression of a range of immunostimulatory
      molecules including MHC class I and II, and CD95 (Fas), but not B7 family
      molecules. Whole PBMC, cultured with allogeneic myoblasts, proliferated, secreted
      IFNgamma, and were cytotoxic. Proliferation and IFNgamma secretion were largely
      dependent on the presence of CD4+ lymphocytes, but neither CD4+ nor CD8+ T cells
      were responsible for cytotoxicity, which was mediated by MHC class II+ non-T
      mononuclear cells. However, purified CD4+ lymphocytes co-cultured with allogeneic
      myoblasts required co-stimulation with anti-CD28 antibodies for proliferation and
      IFNgamma secretion, which only induced a low level of IFNgamma secretion by CD8+
      lymphocytes and did not induce cytotoxic function. These results suggest that
      human myoblasts can act as antigen-presenting cells for naive T lymphocytes, but
      only with additional co-stimulation.

PMID- 9655473
TI  - Selective reduction in CD2 expression on CD2bright/CD8+ lymphocytes from
      cynomolgus monkeys (Macaca fascicularis) in response to acute stress.
AB  - Numerous reports have demonstrated a link between stressful stimuli and immune
      suppression. However, the cellular mechanisms by which stress impairs immune
      function are largely unknown. We have examined the effects of an acute stressor
      on the T cell population, specifically, the number and phenotype of T cells in a
      nonhuman primate model. In nonstressed adult monkeys, we found differences in the
      level of expression of CD2 on T cells, revealing two distinct subsets of T cells,
      CD2dim and CD2bright cells, with CD2bright cells predominately coexpressing CD8.
      In response to acute stress, we observed a significant loss in the number and
      percent of CD2bright/CD8+ cells, with percent of CD2bright cells returning to pre
      stress values within 24 h.

PMID- 9655474
TI  - Is IgG anti-GT1a antibody associated with pharyngeal-cervical-brachial weakness
      or oropharyngeal palsy in Guillain-Barre syndrome?
AB  - The pharyngeal-cervical-brachial variant (PCB) of Guillain-Barre syndrome (GBS)
      has clinical features similar to those of botulism and diphtheria. Mizoguchi et
      al. (1994) [Mizoguchi, K., Hase, A., Obi, T., Matsuoka, H., Takatsu, M.,
      Nishimura, Y., Irie, F., Seyama, Y., Hirabayashi, Y., 1994. Two species of
      antiganglioside antibodies in a patient with a pharyngeal-cervical-brachial
      variant of Guillain-Barre syndrome. J. Neurol. Neurosurg. Psychiatry 57, 1121
      1123] reported a patient with PCB-like symptoms who had serum IgG anti-GT1a
      antibodies which did not cross-react with GQ1b. We assumed that PCB is associated
      with anti-GT1a antibodies that do not have reactivity to GQ1b and made a
      serological study of a PCB patient. We searched for PCB patients prospectively
      and found one with PCB. This patient had IgG anti-GT1a antibodies which were not
      absorbed with GQ1b in an absorption study, whereas IgG anti-GT1a antibodies from
      Fisher's syndrome patients were. The frequency of positive IgG anti-GT1a antibody
      did not differ in patients with and without bulbar palsy. Our findings indicate
      that IgG anti-GT1a antibodies which do not cross-react with GQ1b are specifically
      detectable in PCB and can be used as a diagnostic marker of PCB.

PMID- 9655475
TI  - Human lymphocytes express substance P and its receptor.
AB  - We present data demonstrating the gene expression of substance P (SP) and its
      receptor in human peripheral blood-isolated lymphocytes. Using reverse
      transcribed polymerase chain reaction (RT-PCR) assay, preprotachykinin-A
      (substance-P) mRNA is detected in human peripheral blood-isolated lymphocytes.
      Among the alpha, beta, and gamma transcripts of the SP gene, only the beta and
      gamma transcripts are detectable in these cells. These RT-PCR amplified
      transcripts are recognized by Southern blot assay using a specific SP probe.
      Direct DNA sequence analysis of the RT-PCR products from lymphocytes also
      confirmed the structure of these transcripts which are identical to those found
      in human neuronal cells. At the protein level, human lymphocytes produced
      endogenous SP as determined by an enzyme immunoassay. Capsaicin, a vanillyl fatty
      acid amide (ingredient of hot pepper), released preformed SP from lymphocytes. In
      addition, using RT/nested-PCR analysis, we identified the presence of mRNA for
      neurokinin-1 receptor (the receptor for SP) in human peripheral blood-isolated
      lymphocytes, which was confirmed by Southern blot and DNA sequencing analysis.
      The demonstration that human lymphocytes express SP and its receptor support the
      notion that SP is biologically involved in regulating the functions of these
      cells in an autocrine fashion.

PMID- 9655476
TI  - Specific binding of a 125I-secretoneurin analogue to a human monocytic cell line.
AB  - Secretoneurin (SN) is a novel neuropeptide expressed in the central and
      peripheral nervous system as well as in various endocrine tissues. SN inhibits
      growth of aortic pulmonary and endothelial cells and is a potent chemoattractant
      for endothelial cells, skin fibroblasts and monocytes. We investigated here the
      presence of specific high affinity binding sites for SN on a target tissue. SN
      was iodinated with the Bolton-Hunter (BH) reagent and purified by isocratic
      reversed phase chromatography. Specific binding sites for 125I-BHSN were
      identified on human Mono Mac 6 cells, a monocytic cell line. Scatchard analysis
      revealed a single class of binding sites with a Kd value of 7.3 nM and a Bmax of
      322 (fmol/mg protein). Competition studies demonstrated that the 15 C-terminal
      amino acids of SN could displace authentic SN, whereas shorter fragments were
      inactive. Other sensory neuropeptides like substance P, calcitonin gene-related
      peptide or galanin as well as the chemokine receptor ligand Rantes or the typical
      chemoattractant FMLP could not displace SN. Our studies demonstrate specific high
      affinity binding sites for SN on a monocytic cell line. Since SN exerts a potent
      chemotactic activity towards monocytes and increases cytosolic calcium in these
      cells, these binding sites might well represent a putative functional plasma
      membrane receptor for SN.

PMID- 9655477
TI  - Pathogenesis of acute passive murine encephalomyelitis I. Importance of host
      derived cells as determined by kinetic analysis.
AB  - Kinetics of entry into the CNS of donor- and host-derived T-cells during the
      onset of acute murine EAE induced by the passive transfer of an encephalitogenic
      PLP(139-151)-specific T-cell clone was investigated. RT-PCR and spectratypic
      analysis of total RNA recovered from recipient mice demonstrated the presence in
      the CNS of donor- and host-derived T-cells 24 h post adoptive transfer. Donor
      derived T-cells detected in the CNS decreased days 2-6 post transfer while host
      derived T-cells persisted during this time. Beginning 3 days before clinical
      onset, an increase in the CNS of both T-cell populations was observed which
      persisted through disease onset. Similar analysis performed on recipients of an
      nonencephalitogenic PLP(139-151)-specific T-clone demonstrated a transient
      infiltration of donor- and host-derived T-cells beginning 4 days post transfer
      (dpt) and returning to background levels by day 7 post transfer. Results
      presented here suggest the importance of host-derived T-cells in the onset of
      acute passive murine EAE.

PMID- 9655478
TI  - Endotoxin stimulates an endogenous pathway regulating corticotropin-releasing
      hormone and vasopressin release involving the generation of nitric oxide and
      carbon monoxide.
AB  - Although the administration of endotoxin in vivo activates the neuroendocrine
      stress axis in the process of crosstalk between the immune and endocrine axes,
      the direct application of endotoxin to the hypothalamus in vitro does not
      stimulate the release of the hypothalamic peptides controlling the hypothalamo
      pituitary-adrenal (HPA) axis, corticotropin-releasing hormone (CRH) and
      vasopressin. The hypothesis has therefore been tested that endotoxin may also
      activate inhibitory pathways, specifically those involving the generation of
      nitric oxide (NO) and carbon monoxide (CO). Studies were performed on the
      isolated rat hypothalamus using endotoxin in the presence or absence of
      inhibitors of heme oxygenase (which generates CO) and nitric oxide synthase, and
      ferrous hemoglobin. Endotoxin alone decreased both CRH and vasopressin secretion
      from the hypothalamus. However, when applied together with a nitric oxide
      synthase inhibitor, the inhibitory effect on CRH was lost. Conversely, co
      administration with heme oxygenase inhibitors transformed the inhibition of
      vasopressin to stimulation, while having no effect on the inhibition of CRH.
      Ferrous hemoglobin reversed the inhibition of vasopressin, but did not lead to
      stimulation. It is therefore concluded that endotoxin may stimulate endogenous
      pathways that lead to the generation of NO, which in turn inhibits CRH. In
      addition, it generates CO, which modulates the release of vasopressin. These
      gases are thus potential counter-regulatory controls to the activation of the
      HPA.

PMID- 9655479
TI  - Heat shock proteins come of age: primitive functions acquire new roles in an
      adaptive world.

PMID- 9655480
TI  - Induction of rapid T cell activation and tolerance by systemic presentation of an
      orally administered antigen.
AB  - To understand how orally introduced antigen regulates peripheral immune
      responses, we fed cytochrome c protein to mice transgenic for the beta chain of a
      cytochrome c-specific TCR and followed the antigen-specific T cell responses with
      a cyt c/I-Ek tetramer staining reagent. We find that within 6 hr of cytochrome c
      administration, antigen-specific systemic T cell activation is induced, and
      spleen cells gain the ability to stimulate cytochrome c-specific T cell
      responses. Feeding multiple low doses of cytochrome c down-regulates the systemic
      immune response, which can be correlated with a reduction of antigen-specific T
      cells and not with immune deviation. These results suggest that systemic
      distribution of antigen contributes significantly to oral tolerance induction.

PMID- 9655481
TI  - Detection of antigen-specific T cells with multivalent soluble class II MHC
      covalent peptide complexes.
AB  - Multimeric soluble MHC class II molecules stably occupied with covalently
      attached peptides bind with appropriate specificity to T cell hybridomas and T
      cells from T cell receptor transgenic mice. There is a direct correlation between
      soluble T cell receptor affinity for monomeric MHC/peptide and level of binding
      of multimeric MHC/peptide to T cells. While binding of the multimeric MHC/peptide
      complex is proportional to T cell receptor affinity and expression level, there
      is little influence of T cell CD4.

PMID- 9655482
TI  - Virus-specific CD8+ T cells in primary and secondary influenza pneumonia.
AB  - Virus-specific CD8+ effector T cells (eCTL) are enriched in the lungs of mice
      with primary influenza pneumonia, though later detection of memory T cells (mCTL)
      in the mediastinal lymph nodes (MLN) or spleen by peptide-based staining
      protocols is at the limits of flow cytometric analysis. Respiratory challenge
      with an H3N2 virus months after H1N1 priming induces a massive recall response,
      which reduces virus titers 2-3 days earlier than in nave controls. Influenza
      specific mCTL produce interferon-gamma within 6 hr, but still take 4-5 days to
      localize to the infected respiratory tract. The delay reflects that the recall
      response develops first in the MLN, which contains relatively few mCTL. The
      response to a subdominant epitope is less obvious after secondary challenge.

PMID- 9655483
TI  - Association of DAP12 with activating CD94/NKG2C NK cell receptors.
AB  - While the inhibitory NK cell receptors for MHC class I express immunoreceptor
      tyrosine-based inhibitory motifs that recruit intracellular tyrosine phosphatases
      and prevent NK cell effector function, the activating NK cell receptors lack
      intrinsic sequences required for cellular stimulation. CD94/NKG2C, an activating
      NK cell receptor of the C-type lectin superfamily that binds to HLA-E,
      noncovalently associates with DAP12, a membrane receptor containing an
      immunoreceptor tyrosine-based activating motif. Efficient expression of
      CD94/NKG2C on the cell surface requires the presence of DAP12, and charged
      residues in the transmembrane domains of DAP12 and NKG2C are necessary for this
      interaction. These results provide a molecular basis for the assembly of NK cell
      receptors for MHC class I involved in cellular activation and inhibition.

PMID- 9655484
TI  - Cabin 1, a negative regulator for calcineurin signaling in T lymphocytes.
AB  - Calcineurin plays a pivotal role in the T cell receptor (TCR)-mediated signal
      transduction pathway and serves as a common target for the immunosuppressants
      FK506 and cyclosporin A. We report the identification of a novel endogenous
      calcineurin binding protein named Cabin 1 that inhibits calcineurin-mediated
      signal transduction. The interaction between Cabin 1 and calcineurin is dependent
      on PKC activation. Overexpression of Cabin 1 or its N-terminal truncation mutants
      inhibits the transcriptional activation of calcineurin-responsive elements in the
      interleukin-2 promoter and blocks dephosphorylation of NF-AT upon T cell
      activation. These results suggest a negative regulatory role for Cabin 1 in
      calcineurin signaling and provide a possible mechanism of feedback inhibition of
      TCR signaling through cross-talk between protein kinases and calcineurin.

PMID- 9655485
TI  - T cell receptor gamma gene regulatory sequences prevent the function of a novel
      TCRgamma/pTalpha pre-T cell receptor.
AB  - Expression of a TCRgamma transgene in RAG-1-/- mice resulted in the development
      of a limited number of CD4+CD8+ (DP) thymocytes. In vivo treatments with anti
      TCRgamma antibody enhanced the number of DP thymocytes, demonstrating that
      TCRgamma chains were expressed on the cell surface in the absence of delta,
      alpha, or beta chains. Mutations in pTalpha or CD3epsilon genes abolished
      transgene-induced DP cell development, indicating that TCRgamma can associate
      with pTalpha and CD3 to form a novel pre-TCR. With a transgene containing
      additional regulatory sequences, TCRgamma expression was down-regulated in DP
      cells, and little DP cell development occurred. Thus, the function of the
      endogenous TCRgamma/pTalpha is limited by the transcriptional down-regulation of
      TCRgamma genes that normally accompanies DP cell development.

PMID- 9655486
TI  - Membrane compartmentation is required for efficient T cell activation.
AB  - The plasma membrane of mammalian cells contains detergent-resistant membrane
      rafts enriched in glycosphingolipids and cholesterol. Although several important
      signaling molecules have been found in such rafts, evidence documenting a
      functional role for their localization has been scarce. Using a fractionation
      scheme that preserves tyrosine phosphorylation, we show that T cell activation
      leads to a striking compartmentation in the rafts of activated T cell receptor
      and associated signal-transducing molecules. Conditions that reversibly disrupt
      raft structure either by dispersing their contents or by forcing their
      internalization reversibly disrupt the earliest steps of T cell activation. Thus,
      raft integrity is a prerequisite for efficient T cell receptor signal
      transduction.

PMID- 9655487
TI  - Arrest of B lymphocyte terminal differentiation by CD40 signaling: mechanism for
      lack of antibody-secreting cells in germinal centers.
AB  - Despite extensive research, the role of CD40 signaling in B cell terminal
      differentiation remains controversial. Here we show that CD40 engagement arrests
      B cell differentiation prior to plasma cell formation. This arrest is manifested
      at a molecular level as a reduction in mRNA levels of secretory immunoglobulin
      gene products such as mu(s) and J chain as well as the loss of the
      transcriptional regulator BLIMP-1. Furthermore, the inhibition of B cell
      differentiation by CD40 engagement could not be overcome by either mitogens or
      cytokines, but could be reversed by antibodies that interfere with the CD40/gp39
      interaction. These data suggest that secretory immunoglobulin is not produced by
      B cells that are actively engaged by gp39-expressing T cells.

PMID- 9655488
TI  - Reevaluation of 3'Ekappa function in stage- and lineage-specific rearrangement
      and somatic hypermutation.
AB  - Transgenic studies have led to the conclusion that the 3'Ekappa enhancer
      functions to suppress kappa variable region gene assembly in T lineage cells and
      in progenitor B cells and have also implicated 3'Ekappa as a critical element in
      promoting somatic hypermutation of kappa variable region genes. To assess the
      role of the endogenous 3'Ekappa, we assayed these processes in mice homozygous
      for mutations in which the 3'Ekappa sequences were deleted by the loxP/Cre method
      (3'Ekappa delta/delta mice). In contrast to transgenic findings, we found that
      deletion of the endogenous 3'Ekappa did not deregulate kappa gene rearrangement
      in T lineage cells or in pro-B cells. Furthermore, immunization of the 3'Ekappa
      delta/delta mice led to the generation of specific antibodies with mutation
      patterns typical of affinity maturation, showing that there is no absolute
      requirement for the 3'Ekappa with respect to somatic mutation of endogenous kappa
      genes.

PMID- 9655489
TI  - Affinity dependence of the B cell response to antigen: a threshold, a ceiling,
      and the importance of off-rate.
AB  - Initiation and affinity maturation of the humoral immune response is driven by
      antigen interaction with BCR. To study how signaling and antigen presentation
      through BCR depend on antigen/BCR affinity, lysozyme-specific B cell
      transfectants were challenged with mutated lysozymes differing in their binding
      kinetics. For detectable triggering, the antigen/BCR complex needed a Ka > 10(6)
      M(-1) (dissociation half-life > approximately 1 s). Mutated lysozymes whose
      binding was below this threshold could nevertheless be presented if complexed
      with soluble antibody. Above the threshold, the concentration of antigen required
      to trigger a response decreased as the affinity (particularly dissociation half
      life) increased. However, a plateau was reached at Kas > approximately 10(10) M(
      1) (dissociation half-life > 0.5 hr), supporting the idea of a ceiling to
      affinity maturation.

PMID- 9655490
TI  - In vitro generation of lymphohematopoietic cells from endothelial cells purified
      from murine embryos.
AB  - We have investigated the lymphohematopoietic potentials of endothelial cells (EC)
      and hematopoietic cells (HPC) sorted from embryos. Expression of VE-cadherin,
      CD45, and Ter119 was used to distinguish EC (VE-cadherin+CD45-Ter119-) from HPC
      (VE-cadherin-CD45+). Thus defined, EC population takes up acetylated LDL and
      coexpresses CD31, Flk1, and CD34. In E9.5 embryos, EC from yolk sac (YS) and the
      embryo proper generate blood cells, including lymphocytes. Thus,
      lymphohematopoietic EC do exist in the embryo, and they are generated both in YS
      and the embryo proper. On the other hand, HPC with lymphopoietic potency appear
      first in the embryo proper. These findings implicate involvement of multiple
      environmental cues for acquiring lymphopoietic competency during differentiation
      of HPC.

PMID- 9655491
TI  - Innate immune recognition of bacterial lipopolysaccharide: dependence on
      interactions with membrane lipids and endocytic movement.
AB  - Lipopolysaccharide ([LPS], an endotoxin) from most bacterial species provokes a
      strong inflammatory response in naive animals. LPS from Rhodobacter sphaeroides
      (RsLPS) has a relatively small hydrophobic region and does not stimulate cells or
      animals but instead acts as antagonist of LPS action. Here, we show that the
      activity of RsLPS is transformed from antagonist to full agonist by the addition
      of chlorpromazine (CPZ) and other cationic membrane-active agents. In addition,
      while LPS is rapidly transported from the plasma membrane to an intracellular
      site, we find that RsLPS is not transported but instead remains in the cell
      periphery. Addition of CPZ also reverses this behavior, causing RsLPS to be
      transported to a perinuclear site. The data suggest that the interaction of LPS
      with membrane lipids is influenced by membrane-modifying agents such as CPZ, and
      these interactions dictate both its intracellular transport and its ability to
      stimulate cellular responses.

PMID- 9655492
TI  - fMRI of monkey visual cortex.
AB  - While functional magnetic resonance imaging (fMRI) is now used widely for
      demonstrating neural activity-related signals associated with perceptual, motor,
      and cognitive processes in humans, to date this technique has not been developed
      for use with nonhuman primates. fMRI in monkeys offers a potentially valuable
      experimental approach for investigating brain function, which will complement and
      aid existing techniques such as electrophysiology and the behavioral analysis of
      the effects of brain lesions. There are, however, a number of significant
      technical challenges involved in using fMRI with monkeys. Here, we describe the
      procedures by which we have overcome these challenges to carry out successful
      fMRI experiments in an alert monkey, and we present the first evidence of
      activity-related fMRI signals from monkey cerebral cortex.

PMID- 9655493
TI  - Synaptic adhesion: the building blocks of memory?

PMID- 9655494
TI  - Null mutations lacking substance: elucidating pain mechanisms by genetic
      pharmacology.

PMID- 9655495
TI  - Experience-dependent plasticity and the maturation of glutamatergic synapses.

PMID- 9655496
TI  - Genes, brain, and mind: the evolution of cognition.

PMID- 9655497
TI  - Pathfinding of olfactory neuron axons to stereotyped glomerular targets revealed
      by dynamic imaging in living zebrafish embryos.
AB  - In the vertebrate olfactory system, sensory neurons with common odorant
      specificities project to specific glomeruli in the olfactory bulb. How do
      olfactory sensory neurons find their glomerular targets? To address this
      question, we have visualized the genesis of the peripheral olfactory system in
      living zebrafish embryos. Dye labelings reveal that a primordial yet stereotyped
      map of glomeruli is apparent during embryogenesis. By labeling a small number of
      cells with an ectopically expressed green fluorescent protein reporter, we can
      observe the dynamic growth behaviors of individual olfactory neuron growth cones
      as they project to their glomeruli. We find that olfactory axons extend directly
      to their partner glomeruli, suggesting that these cells' growth cones rely upon
      pathfinding cues to reach their targets.

PMID- 9655498
TI  - Corticotropin releasing factor receptor 1-deficient mice display decreased
      anxiety, impaired stress response, and aberrant neuroendocrine development.
AB  - Corticotropin releasing factor (CRF) is a major integrator of adaptive responses
      to stress. Two biochemically and pharmacologically distinct CRF receptor subtypes
      (CRFR1 and CRFR2) have been described. We have generated mice null for the CRFR1
      gene to elucidate the specific developmental and physiological roles of CRF
      receptor mediated pathways. Behavioral analyses revealed that mice lacking CRFR1
      displayed markedly reduced anxiety. Mutant mice also failed to exhibit the
      characteristic hormonal response to stress due to a disruption of the
      hypothalamic-pituitary-adrenal (HPA) axis. Homozygous mutant mice derived from
      crossing heterozygotes displayed low plasma corticosterone concentrations
      resulting from a marked agenesis of the zona fasciculata region of the adrenal
      gland. The offspring from homozygote crosses died within 48 hr after birth due to
      a pronounced lung dysplasia. The adrenal agenesis in mutant animals was
      attributed to insufficient adrenocorticotropic hormone (ACTH) production during
      the neonatal period and was rescued by ACTH replacement. These results suggest
      that CRFR1 plays an important role both in the development of a functional HPA
      axis and in mediating behavioral changes associated with anxiety.

PMID- 9655499
TI  - Three period homologs in mammals: differential light responses in the
      suprachiasmatic circadian clock and oscillating transcripts outside of brain.
AB  - We have cloned and characterized the mouse cDNA of a third mammalian homolog of
      the Drosophila period gene and designated it mPer3. The mPER3 protein shows
      approximately 37% amino acid identity with mPER1 and mPER2 proteins. The three
      mammalian PER proteins share several regions of sequence homology, and each
      contains a protein dimerization PAS domain. mPer3 RNA levels oscillate in the
      suprachiasmatic nuclei (SCN) and eyes. In the SCN, mPer3 RNA levels are not
      acutely altered by light exposure at different times during subjective night.
      This contrasts with the acute induction by light of mPer1 and mPer2 RNA levels
      during early and late subjective night. mPer3 is widely expressed in tissues
      outside of brain. In liver, skeletal muscle, and testis, mPer RNAs exhibit
      prominent, synchronous circadian oscillations. The results highlight the
      differential light responses among the three mammalian Per genes in the SCN and
      raise the possibility of circadian oscillators in mammals outside of brain and
      retina.

PMID- 9655500
TI  - Subunit composition, protein interactions, and structures of the mammalian brain
      sec6/8 complex and septin filaments.
AB  - Both the sec6/8 complex and septin filaments have been implicated in directing
      vesicles and proteins to sites of active membrane addition in yeast. The rat
      brain sec6/8 complex coimmunoprecipitates with a filament composed of four
      mammalian septins, suggesting an interaction between these complexes. One of the
      septins, CDC10, displays broad subcellular and tissue distributions and is found
      in postmitotic neurons as well as dividing cells. Electron microscopic studies
      showed that the purified rat brain septins form filaments of 8.25 nm in diameter;
      the lengths of the filaments are multiples of 25 nm. Glutaraldehyde-fixed rat
      brain sec6/8 complex adopts a conformation resembling the letter "T" or "Y". The
      sec6/8 and septin complexes likely play an important role in trafficking vesicles
      and organizing proteins at the plasma membrane of neurons.

PMID- 9655501
TI  - Real time imaging of calcium-induced localized proteolytic activity after axotomy
      and its relation to growth cone formation.
AB  - The emergence of a neuronal growth cone from a transected axon is a necessary
      step in the sequence of events that leads to successful regeneration. Yet, the
      molecular mechanisms underlying its formation after axotomy are unknown. In this
      study, we show by real time imaging of the free intracellular Ca2+ concentration,
      of proteolytic activity, and of growth cone formation that the activation of
      localized and transient Ca2+-dependent proteolysis is a necessary step in the
      cascade of events that leads to growth cone formation. Inhibition of this
      proteolytic activity by calpeptin, a calpain inhibitor, abolishes growth cone
      formation. We suggest that calpain plays a central role in the reorganization of
      the axon's cytoskeleton during its transition from a stable differentiated
      structure into a dynamically extending growth cone.

PMID- 9655502
TI  - Diversity revealed by a novel family of cadherins expressed in neurons at a
      synaptic complex.
AB  - In mammals, neurons are highly differentiated and play distinctive functions even
      in the same brain region. We found a novel cadherin-related neuronal receptor
      (Cnr) gene family by studying Fyn-binding activity in mouse brain. CNR1 protein
      is located in the synaptic junction and forms a complex with Fyn. Sequence
      analysis of eight Cnr products of approximately 20 genes indicates that these
      comprise a novel cadherin family of the cadherin superfamily. The expression
      patterns of each member of this novel family were grossly similar to each other
      but restricted to subpopulations of neurons of the same type. The diversity of
      the Cnr family genes suggests that there are molecular mechanisms that govern
      highly differentiated neural networks in the mammalian CNS.

PMID- 9655503
TI  - Structure-function analysis of cell adhesion by neural (N-) cadherin.
AB  - To investigate the possible biological function of the lateral "strand dimer"
      observed in crystal structures of a D1 domain extracellular fragment from N
      cadherin, we have undertaken site-directed mutagenesis studies of this molecule.
      Mutation of most residues important in the strand dimer interface abolish the
      ability of N-cadherin to mediate cell adhesion. Mutation of an analogous central
      residue (Trp-2) in E-cadherin also abrogates the adhesive capacity of that
      molecule. We also determined the crystal structure of a Ca2+-complexed two-domain
      fragment from N-cadherin. This structure, like its E-cadherin counterpart, does
      not adopt the strand dimer conformation. This suggests the possibility that
      classical cadherins might stably exist in both dimeric and monomeric forms. Data
      from several laboratories imply that lateral dimerization or clustering of
      cadherins may increase their adhesivity. We suggest the possibility that the
      strand dimer may play a role in this activation.

PMID- 9655504
TI  - A role for the cadherin family of cell adhesion molecules in hippocampal long
      term potentiation.
AB  - The cadherins are a family of cell-cell adhesion molecules that mediate Ca2+
      dependent homophilic interactions between cells and transduce signals by
      interacting with cytoplasmic proteins. In the hippocampus, immunostaining
      combined with confocal microscopy revealed that both neural- (N-) and epithelial-
      (E-) cadherin are present at synaptic sites, implying a role in synaptic
      function. Pretreatment of hippocampal slices with antibodies (Abs) raised against
      the extracellular domain of either N-cad or E-cad had no effect on basal synaptic
      properties but significantly reduced long-term potentiation (LTP). Infusion of
      antagonistic peptides containing the His-Ala-Val (HAV) consensus sequence for
      cadherin dimerization also attenuated LTP induction without affecting previously
      established LTP. Because the intense synaptic stimulation associated with LTP
      induction might transiently deplete extracellular Ca2+ and hence potentially
      destabilize cadherin-cadherin interactions, we examined whether slices could be
      protected from inhibition by N-cad Abs or HAV peptides by raising the
      extracellular Ca2+ concentration. Indeed, we found that high extracellular Ca2+
      prevented the block of LTP by these agents. Taken together, these results
      indicate that cadherins are involved in synaptic plasticity, and the stability of
      cadherin-cadherin bonds may be regulated by synaptic stimulation.

PMID- 9655505
TI  - Strength and orientation tuning of the thalamic input to simple cells revealed by
      electrically evoked cortical suppression.
AB  - Is thalamic input to the visual cortex strong and well tuned for orientation, as
      predicted by Hubel and Wiesel's (1962) model of orientation selectivity in simple
      cells? We directly measured the size of the thalamic input to single simple cells
      intracellularly by combining electrical stimulation of the cortex with a briefly
      flashed visual stimulus. In nearby cells, the electrical stimulation evoked a
      long-lasting inhibition that prevented them from firing in response to the visual
      stimulus. The visually evoked excitatory postsynaptic potentials (EPSPs) recorded
      during the period of cortical suppression, therefore, reflected largely the
      thalamic input. In 16 neurons that received monosynaptic input from the thalamus,
      cortical suppression left 46% of normal visual response on average (12%-86% in
      range). In those cells tested, this remaining visual response was as well tuned
      for orientation as the normal response to the visual stimulus alone. We conclude
      that the thalamic input to cortical simple cells with monosynaptic input from the
      thalamus is strong and well tuned in orientation, and that the intracortical
      input does not appear to sharpen orientation tuning in these cells.

PMID- 9655506
TI  - Attention and perceptual learning modulate contextual influences on visual
      perception.
AB  - Brightness discrimination thresholds and facilitation by lateral interaction were
      measured in five human observers and two monkeys. The subjects judged the
      brightness of one of four peripherally seen lines against a reference. This
      experiment was performed both when the observer was cued to the position of the
      test line (focused attention) and when there was no cue (distributed attention).
      Discrimination was better with focused than with distributed attention. When the
      test line had a collinear flank, its brightness was enhanced; this enhancement
      was four times more prominent with distributed than with focused attention. After
      training, thresholds improved and collinear facilitation decreased under
      distributed but not under focused attention. The findings show that there are
      fewer benefits from contextual interaction once attention is directed toward a
      visual location, and that the attentional effects are subject to training.

PMID- 9655507
TI  - Impaired cerebellar long-term potentiation in type I adenylyl cyclase mutant
      mice.
AB  - Activation of adenylyl cyclase and the consequent production of cAMP is a process
      that has been shown to be central to invertebrate model systems of information
      storage. In the vertebrate brain, it has been suggested that a presynaptic
      cascade involving Ca influx, cAMP production, and subsequent activation of cAMP
      dependent protein kinase is necessary for induction of long-term potentiation
      (LTP) at the cerebellar parallel fiber-Purkinje cell synapse. We have used mutant
      mice in which the major Ca-sensitive adenylyl cyclase isoform of cerebellar
      cortex (type I) is deleted to show that this results in an approximately 65%
      reduction in cerebellar Ca-sensitive cyclase activity and a nearly complete
      blockade of cerebellar LTP assessed using granule cell-Purkinje cell pairs in
      culture. This blockade is not accompanied by alterations in a number of basal
      electrophysiological parameters and may be bypassed by application of an
      exogenous cAMP analog, suggesting that it results specifically from deletion of
      the type I adenylyl cyclase.

PMID- 9655508
TI  - Kainate receptor modulation of GABA release involves a metabotropic function.
AB  - The mechanism through which kainate receptors downregulate the release of GABA in
      the hippocampus is not known. We have found that the action of kainate on the
      hippocampal inhibitory postsynaptic current (IPSC) is mediated by a metabotropic
      process that is sensitive to Pertussis toxin (PTx) and independent of ion channel
      current. The downregulation of GABA IPSCs by kainate was also prevented in a dose
      dependent manner by calphostin C, a specific inhibitor of PKC, and the inhibition
      of phospholipase C (PLC) drastically reduced the action of kainate. The effect of
      kainate was completely occluded by phorbol esters and by increasing extracellular
      Ca2+ but remained unaltered after inhibition or activation of protein kinase A
      (PKA). These results demonstrate that the activation of kainate receptors
      triggers a second messenger cascade, which results in the stimulation of PKC, and
      therefore document a metabotropic action of kainate receptors, which results in
      the inhibition of GABA release.

PMID- 9655509
TI  - Synaptic defects and compensatory regulation of inositol metabolism in inositol
      polyphosphate 1-phosphatase mutants.
AB  - Phosphoinositides function as important second messengers in a wide range of
      cellular processes. Inositol polyphosphate 1-phosphatase (IPP) is an enzyme
      essential for the hydrolysis of the 1-phosphate from either Ins(1,4)P2 or
      Ins(1,3,4)P3. This enzyme is Li+ sensitive, and is one of the proposed targets of
      Li+ therapy in manic-depressive illness. Drosophila ipp mutants accumulate IP2 in
      their system and are incapable of metabolizing exogenous Ins(1,4)P2. Notably, ipp
      mutants demonstrate compensatory upregulation of an alternative branch in the
      inositol-phosphate metabolism tree, thus providing a means of ensuring continued
      availability of inositol. We demonstrate that ipp mutants have a defect in
      synaptic transmission resulting from a dramatic increase in the probability of
      vesicle release at larval neuromuscular junctions. We also show that Li+
      phenocopies this effect in wild-type synapses. Together, these results support a
      role for phosphoinositides in synaptic vesicle function in vivo and
      mechanistically question the "lithium hypothesis."

PMID- 9655510
TI  - The nematode degenerin UNC-105 forms ion channels that are activated by
      degeneration- or hypercontraction-causing mutations.
AB  - Nematode degenerins have been implicated in touch sensitivity and other forms of
      mechanosensation. Certain mutations in several degenerin genes cause the
      swelling, vacuolation, and death of neurons, and other mutations in the muscle
      degenerin gene unc-105 cause hypercontraction. Here, we confirm that unc-105
      encodes an ion channel and show that it is constitutively active when mutated.
      These mutations disrupt different regions of the channel and have different
      effects on its gating. The UNC-105 channels are permeable to small monovalent
      cations but show voltage-dependent block by Ca2+ and Mg2+. Amiloride also
      produces voltage-dependent block, consistent with a single binding site 65% into
      the electric field. Mammalian cells expressing the mutant channels accumulate
      membranous whorls and multicompartment vacuoles, hallmarks of degenerin-induced
      cell death across species.

PMID- 9655511
TI  - Cytosolic Ca2+ acts by two separate pathways to modulate the supply of release
      competent vesicles in chromaffin cells.
AB  - Recovery from depletion of the readily releasable pool of vesicles (RRP) in
      adrenal chromaffin cells was studied at differing basal [Ca2+]i or following
      protein kinase C (PKC) activation by phorbol esters. Following depletion, the
      pool size was estimated at varied times from cell capacitance jumps in response
      to paired depolarizations. The experimentally observed RRP recovery time course
      and steady-state size could be predicted from the measured [Ca2+]i signal
      assuming a Michaelis-Menten-type regulation of the vesicle supply by Ca2+. An
      elevated recruitment activity was observed at increased [Ca2+]i even when protein
      kinase C was blocked, but maximum effects could be obtained only after
      stimulation of PKC by phorbol esters or by prolonged elevations in [Ca2+]i. We
      suggest that, in chromaffin cells, elevated cytosolic Ca2+ modulates exocytotic
      plasticity via PKC-dependent and -independent pathways.

PMID- 9655512
TI  - Localized secretion of ATP and opioids revealed through single Ca2+ channel
      modulation in bovine chromaffin cells.
AB  - In bovine chromaffin cells, the Ca2+ channels involved in exocytosis are
      effectively inhibited by ATP and opioids that are coreleased with catecholamines
      during cell activity. This autocrine loop causes a delay in Ca2+ channel
      activation that is quickly removed by preceding depolarizations. Changes in Ca2+
      channel gating by secreted products thus make it possible to correlate Ca2+
      channel activity to secretory events. Here, using cell-attached patch recordings,
      we found a remarkable correlation between delayed Ca2+ channel openings and
      neurotransmitter secretion induced by either local or whole-cell Ba2+
      stimulation. The action is specific for N- and P/Q-type channels and largely
      prevented by PTX and mixtures of purinergic and opioid receptor antagonists.
      Overall, our data provide evidence that exocytosis, viewed through the autocrine
      inhibition of non-L-type channels, is detectable in membrane patches of
      approximately 1 microm2 distributed over 30%-40% of the total cell surface, while
      Ca2+ channels and autoreceptors are uniformly distributed over most of the cell
      membrane.

PMID- 9655513
TI  - The location of the gate in the acetylcholine receptor channel.
AB  - The cation-conducting channel of the nicotinic acetylcholine (ACh) receptor is
      lined by the first (M1) and second (M2) membrane-spanning segments of each of its
      five subunits. Six consecutive residues, alphaS239 to alphaT244, in the alpha
      subunit M1-M2 loop and at the intracellular end of M2 were mutated to cysteine.
      The accessibility of the substituted cysteines were probed with small, cationic,
      sulfhydryl-specific reagents added extracellularly and intracellularly. In the
      closed state of the channel, there is a barrier to these reagents added from
      either side between alphaG240 and alphaT244. ACh induces the removal of this
      barrier, which acts as an activation gate. The residues alphaG240, alphaE241,
      alphaK242, and alphaT244 line a narrow part of the channel, in which this gate is
      located.

PMID- 9655514
TI  - Three transmembrane conformations and sequence-dependent displacement of the S4
      domain in shaker K+ channel gating.
AB  - We have acquired structural evidence that two components evident previously in
      the depolarization-evoked gating currents from voltage-gated Shaker K+ channels
      have their origin in sequential, two-step outward movements of the S4 protein
      segments. A point mutation greatly destabilizes the "fully retracted" state of S4
      transmembrane translocation, causing instead an intermediate state to predominate
      at resting potentials. This state is distinguishable topologically and
      fluorometrically. That a point mutation effectively excludes half the range of S4
      motion from physiological voltages suggests that the diverse sensitivities among
      voltage-gated channels might reflect not only differences in S4 valence, but also
      displacement. Existence of an intermediate subunit state helps explain why
      modeling channel activation has required positing greater than four closed
      states.

PMID- 9655515
TI  - Spatiotemporal measurement of free radical elimination in the abdomen using an in
      vivo ESR-CT imaging system.
AB  - Electron spin resonance (ESR) imaging can visualize the distribution of free
      radicals in living systems according to their concentrations. However, the
      application of ESR imaging to living animals has not been well established. Using
      a rapid field scan L-band ESR imaging system, we have successfully obtained two
      dimensional ESR projection (xz-plane projection) and three-dimensional ESR-CT
      (trans-axial section along the y-axis) images of the abdomen of living mice after
      an injection of 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (carbamoyl
      PROXYL) into the tail vein. The in vivo two-dimensional ESR projection imaging
      clearly visualized the carbamoyl-PROXYL distribution and the rapid decay process
      in the abdomen. Because among the viscera, the liver is most abundantly
      associated with a blood volume, the outline of the image can be composed mainly
      of this organ. We therefore attempted to find whether there will be a difference
      in spatiotemporal dynamics of carbamoyl-PROXYL in the abdomens between the
      control and the mice with liver damage by two-dimensional ESR projection. In the
      control mice, carbamoyl-PROXYL was almost completely eliminated from the abdomen
      within 5 minutes after administration. On the other hand, in mice with carbon
      tetrachloride-damaged livers, the decay of carbamoyl-PROXYL was markedly
      prolonged. Even at 5 min after administration, carbamoyl-PROXYL remained clearly
      visible in the abdomen. In vivo three-dimensional ESR-CT imaging showed an even
      distribution of carbamoyl-PROXYL throughout the whole liver, which corresponded
      well with the images of trans-axial sections of the murine abdomen. We have
      succeeded in displaying two-dimensional ESR projection and three-dimensional ESR
      CT images of carbamoyl-PROXYL distribution and clearance in the abdomen of a
      living animal. The ESR-CT imaging technique is considered to be a powerful new
      tool for noninvasive investigations of the in vivo spatiotemporal dynamics of
      free radical distribution and elimination in the organs.

PMID- 9655516
TI  - Total antioxidant capacity of serum increased in early but not late period after
      intestinal ischemia in rats.
AB  - The ischemia of small intestine was induced in anesthetized Wistar rats by
      occluding the superior mesenteric artery for 45 min and then the reperfusion was
      set. Serum samples were obtained at the end of the ischemic period and also
      during early (1 to 4 h) and late postischemic period (1 to 4 d). The total
      antioxidant capacity (TRAP) of serum samples was evaluated using luminol enhanced
      chemiluminescence. The increased mobilization of phagocytic cells and the release
      of reactive oxygen species into the circulation was observed from the first and
      second hour of the postischemic period, respectively. Nevertheless, the activity
      of natural antioxidant mechanisms of serum was already elicited at the end of the
      ischemic period. Furthermore, the TRAP of serum increased with the increasing
      duration of early postischemic period. Among the antioxidants studied, urate and
      ascorbate concentrations exerted the highest correlation with TRAP, but 31.6% of
      the total antioxidant capacity remained for the activity of an unidentified
      antioxidant(s). After being exhausted, the TRAP of serum oscillated around the
      preoperation level at days 1-4 of the postischemic period. The increase in total
      antioxidant capacity of serum induced by oxidative stress was sufficient to
      prevent lipoperoxidation both in serum and intestinal tissue.

PMID- 9655517
TI  - Quercetin glucosides interact with the intestinal glucose transport pathway.
AB  - Flavonols are efficient antioxidants with the potential to protect biological
      macromolecules from oxidative damage in vivo, and if absorbed into the
      circulation they may protect against cardiovascular disease. Although flavonol
      aglycones are present in foods at low concentrations, their glycosides are
      abundant in onions, apples, beans and tea, and are thought to be stable under the
      conditions of the human stomach and small bowel. There is, however, recent
      evidence to suggest that intact glycosides of quercetin may be absorbed from the
      small intestine by a mechanism involving the glucose transport pathway. In the
      present study we tested this hypothesis by measuring the effect of quercetin
      glycosides on the rate of efflux of galactose from the jejunal mucosa. Everted
      sacs of rat jejunum preloaded with 14C-galactose were exposed to quercetin
      glycosides isolated from onions. Quercetin mono- and diglucosides were shown to
      accelerate the carrier-mediated efflux of galactose via a sodium-dependent
      pathway. HPLC analysis confirmed the stability of the glycosides under conditions
      simulating those in the upper alimentary tract. These studies suggest that
      purified quercetin glucosides are capable of interacting with the sodium
      dependent glucose transport receptors in the mucosal epithelium and may therefore
      be absorbed by the small intestine in vivo.

PMID- 9655518
TI  - Reoxygenation-induced mitochondrial damage is caused by the Ca2+-dependent
      mitochondrial inner membrane permeability transition.
AB  - Anoxia/reoxygenation injury of isolated rat liver mitochondria was investigated.
      During anoxia of up to 60 min, the membrane potential was largely preserved and
      mitochondrial swelling was not observed. Reoxygenation of anoxic mitochondria
      rapidly caused swelling, cyclosporin A-sensitive Ca2+ efflux, [14C]sucrose
      trapping, and loss of the membrane potential along with increased generation of
      reactive oxygen intermediates (ROI). Although pretreatment with catalase and
      superoxide dismutase completely abolished reoxygenation-induced generation of
      ROI, mitochondrial damage was not prevented, as indicated by swelling, loss of
      the membrane potential, a decrease of the ATP content, and cyclosporin A
      sensitive Ca2+ efflux. However, addition of the immunosuppressant cyclosporin A
      or addition of ADP completely prevented the mitochondrial damage induced by
      reoxygenation. The same protective effect was noted when Ca2+ cycling was
      prevented, either by chelating Ca2+ with EGTA or by inhibiting Ca2+ reuptake with
      ruthenium red. These findings indicate that mitochondrial anoxia/reoxygenation
      injury is caused by the cyclosporin A-sensitive and Ca2+-dependent membrane
      permeability transition. In contrast, reoxygenation injury does not appear to be
      triggered by the enhanced production of ROI.

PMID- 9655520
TI  - 4-Hydroxynonenal modifies the effects of serum growth factors on the expression
      of the c-fos proto-oncogene and the proliferation of HeLa carcinoma cells.
AB  - In this study, the effect of 4-hydroxynonenal (HNE), a peroxidation product of
      omega-6-poly-unsaturated fatty acids, on the expression of the c-fos proto
      oncogene and growth factor-induced proliferation of HeLa carcinoma cells in vitro
      was investigated. The Fos protein forms the heterodimer AP-1 with the Jun protein
      and regulates the cell cycle by inducing cyclin D1. Agents that are able to
      induce c-fos include serum, platelet-derived growth factor (PDGF), and epidermal
      growth factor (EGF), all of which were used in this study. The proliferation rate
      was determined by cell counting (viable and dead cells according to trypan blue
      exclusion) and the BrdU assay. The c-fos mRNA level was monitored by the reverse
      transcriptase/polymerase chain reaction. In the absence of HNE, serum-deprived
      cells responded to serum stimulation with a more than 10-fold increase of the c
      fos mRNA level as well as with an increased rate of DNA synthesis and cell
      multiplication. Both EGF and PDGF (applied in combination with insulin) were able
      to substitute for FCS and induced rapid growth of the tumor cells preincubated in
      serum-deprived medium. In the absence of growth factors a negative correlation
      between the HNE concentration (range: 1-250 microM) and the c-fos mRNA level was
      observed. We suppose that HNE interferes in this case with the basal activity of
      the c-fos promoter. EGF, when applied after the HNE treatment, induced rapid
      growth of the tumor cells preincubated in serum-free medium, if HNE was used in a
      physiological concentration (1 microM). No difference was observed compared to
      the HNE-free control. c-fos mRNA level was nearly unchanged. In contrast, a
      cytotoxic concentration of the aldehyde (100 microM) caused a complete inhibition
      of proliferation, although a twofold increase of the c-fos mRNA level immediately
      after the aldehyde treatment was observed. A similar effect of HNE in cytotoxic
      concentration on c-fos expression was observed when cells were grown in presence
      of PDGF instead of EGF. Hence, in both cases HNE possibly interferes with the
      signal transduction pathway, which is initiated by external growth factors. The
      increased c-fos expression might be part of an abortive attempt to overcome the
      stressful condition raised by a cytotoxic concentration of HNE.

PMID- 9655519
TI  - Chemical analysis of multiple sclerosis lesions by FT-IR microspectroscopy.
AB  - Fourier transform infrared microspectroscopy can be used to collect infrared
      spectra from microscopic regions of tissue sections. If spectra are collected
      along a grid pattern, then maps of chemical functional groups can be produced and
      correlated to tissue histopathology. In the present study, white matter from
      multiple sclerosis and control brains were examined. Mapping experiments were
      designed such that 17 spectra were collected at 200 microm intervals along a line
      that was partially or wholly within a multiple sclerosis lesion site or within a
      representative white matter region of control tissue. Data analysis was based on
      earlier in vitro studies which found that the carbonyl at 1740 cm(-1) increases
      when lipids become oxidized (Free Rad. Biol. Med. 16:591-601, 1994), and the
      amide I peak at approximately 1660 cm(-1) broadens when proteins become oxidized
      (FEBS Let. 362:165-170, 1995). The results indicated that the C=O to CH2 ratio
      (1740 cm(-1):1468 cm(-1)) was elevated at several collection points in lesion
      sites from multiple sclerosis brains compared to values from white matter of
      control brains. Inspection of the amide I peak at 1657 cm(-1) revealed that it
      was broadened towards 1652 cm(-1) in multiple sclerosis tissues but not control
      tissues. These results suggest that lipids and proteins could be oxidized at
      active multiple sclerosis lesion sites. The localization of these products to
      lesion sites supports a role for free radicals in the pathogenesis of multiple
      sclerosis.

PMID- 9655521
TI  - Effect of bile acids on lipid peroxidation: the role of iron.
AB  - The toxic effect of hydrophobic bile acids is claimed to be in part mediated by
      lipid peroxidation. Conversely, antioxidant properties of tauroursodeoxycholic
      acid (TUDC), a hydrophilic bile acid, have been suggested as a possible mechanism
      by which TUDC confers its beneficial effect in a variety of diseases. We have
      investigated the effect of taurodeoxycholic acid (TDC), a hydrophobic bile acid
      and TUDC on lipid peroxidation using a pure lipid system both in the presence and
      absence of iron ions. Neither TDC nor TUDC showed any effect on spontaneous lipid
      peroxidation of phosphatidylcholine liposomes or sodium arachidonate solution.
      This lack of effect excludes the possibility of direct prooxidant or antioxidant
      properties for TDC and TUDC. Addition of ferrous ions (0.1 mM) to the lipid
      system brought about a linear increase in lipid peroxidation with time. The
      presence of TDC caused an increase in the rate and extent of iron-stimulated
      lipid peroxidation. The propensity of bile acids to increase iron-induced lipid
      peroxidation was related to hydrophobicity of the individual bile acids, with the
      highest effect observed with taurolithocholic acid, whereas TUDC did not have any
      influence. The TDC-induced increase in the iron-stimulated lipid peroxidation was
      concentration dependent. Addition of TUDC (10 mM) completely abolished the effect
      of TDC (2 mM) on iron-induced lipid peroxidation. This finding suggests that TUDC
      does not function as an antioxidant per se but may prevent lipid peroxidation
      caused by TDC. In conclusion, only in the presence of iron ions, hydrophobic bile
      acids may enhance lipid peroxidation. TUDC has no antioxidant activity per se but
      may counter the TDC-induced increase in iron-stimulated lipid peroxidation.

PMID- 9655522
TI  - TNF-induced mitochondrial changes and activation of apoptotic proteases are
      inhibited by A20.
AB  - A20 zinc finger protein is a product of a cytokine-induced primary response gene.
      It functions as a negative regulator of the tumor necrosis factor (TNF)
      inhibiting both TNF-mediated apoptosis and activation of transcription factors.
      We demonstrated that A20 overexpression blocks early TNF-induced signaling events
      including the generation of free radicals, the fall in mitochondrial
      transmembrane potential (delta psi(m)), and the activation of caspase-3-like
      apoptotic proteases. General inhibitor of caspases, cow pox virus-derived CrmA,
      also inhibited TNF-induced mitochondrial changes indicating that early caspase
      activation occurs upstream from mitochondrial changes. Interestingly, changes in
      mitochondrial function or induction of caspase-3-like activity induced by anti
      Fas or doxorubicin were not inhibited by A20. The data show that A20 is a
      specific inhibitor of TNF signaling and acts upstream of INF-induced free radical
      formation, fall in mitochondrial transmembrane potential (delta psi(m)), and
      activation of caspase-3-like proteases.

PMID- 9655523
TI  - Does beta-carotene protect membrane lipids from nitrogen dioxide?
AB  - Lipid peroxidation in rat liver microsomes, induced by nitrogen dioxide (NO2), a
      free radical toxin, was examined in the absence and in the presence of varying
      concentrations of beta-carotene. The extent of peroxidation was assayed by
      determining the malonaldehyde formed as thiobarbituric acid reactive substances
      (TBARS). When the concentration of beta-carotene was 13.8 and 43.1 nmol/mg
      protein, no protection was seen, rather an increase of 10% and 30%, respectively,
      in TBARS was observed as compared with the normal microsomes containing no beta
      carotene. However, at beta-carotene concentrations of 66.5 and 89.4 nmol/mg
      protein, only a marginal increase of 9% and 4% in TBARS, respectively, was
      observed. The amount of beta-carotene consumed during peroxidation, determined by
      following the absorbance at 450 nm, was found to increase linearly with increased
      exposure to NO2. The direct reaction of NO2 with beta-carotene was studied in an
      inert organic solvent, acetonitrile, by following the absorption spectrum of beta
      carotene in the wavelength region 220-600 nm. The rate of loss of beta-carotene
      was found to be much faster than that in microsomes. The results suggest that in
      in vitro systems, the reaction of secondary lipid-derived radicals with beta
      carotene and their relative competition for NO2 plays an important role in the
      actual function of beta-carotene as a prooxidant or an antioxidant. Another lipid
      soluble antioxidant, alpha-tocopherol (vitamin-E), showed significant protection
      against NO2-induced lipid peroxidation at a concentration of 45 nmol/mg protein
      under these conditions.

PMID- 9655524
TI  - Preparation and EPR studies of lithium phthalocyanine radical as an oxymetric
      probe.
AB  - The electron paramagnetic resonance (EPR) spectrum of the paramagnetic center in
      solid lithium phthalocyanine, LiPc, exhibits a pO2 (partial pressure of oxygen)
      dependent line width. The compound is insoluble in water and is not easily
      biodegradable and, therefore, is a useful spin probe for quantitative in vivo
      oxymetry. Because EPR spectrometry is potentially a useful technique to
      quantitatively obtain in vivo tissue pO2, such probes can be used to obtain
      physiological information. In this paper, a simple experimental procedure for the
      preparation of LiPc using potentiostatic electrochemical methods is described.
      The setup was relatively inexpensive and easy to implement. A constant potential
      ranging from 0.05 to 0.75 V versus Ag+/AgCl(s) was used for obtaining LiPc. The
      EPR spectral studies were carried out using spectrometers operating at X-band and
      at radiofrequency (RF) at different pO2 values to characterize the spectral
      response of these crystals. The results indicate that, depending on the
      electrolysis conditions, the products contain mixtures of crystals exhibiting pO2
      sensitive and pO2-insensitive line widths. Electrolysis conditions are reported
      whereby the pO2-sensitive LiPc crystals were the predominant product. The
      influence of the working surface of the electrode and the electrolysis time on
      the yield were also evaluated. The crystals of LiPc were also studied using a
      time-domain RF EPR spectrometer. In time-domain EPR, the signals that survive
      beyond the spectrometer dead time are mainly the narrow lines corresponding to
      the pO2-sensitive crystals, whereas the signals arising from the pO2-insensitive
      component of LiPc were found not to survive beyond the spectrometer dead time.
      This signal survival makes the time-domain EPR method more sensitive for pO2
      measurements using LiPc because the line width becomes very narrow at very low
      pO2 and, concomitantly, the relaxation time T2 longer, with no modulation or
      power saturation artifacts that are encountered as in the continuous wave (cw)
      mode. Further, minimal contributions from object motion in the spectral data
      obtained using time-domain methods make it an advantage for in vivo applications.

PMID- 9655525
TI  - Oxidative damage in tissues of rats exposed to cigarette smoke.
AB  - Cigarette smoke is known to contain high concentrations of free radicals and
      oxidants. To examine the oxidative effect of cigarette smoking, we subjected rats
      to inhalation of cigarette smoke, and measured cellular free glutathione, the
      degree of protein S-thiolation, and 8-oxo-2'-deoxyguanosine (oxo8dG) in DNA.
      Inhalation of the cigarette smoke for 30 days, three times a day, resulted in a
      significant decrease of the total free glutathione contents in tissues,
      especially in the lung. Elevated levels of oxidized glutathione and protein S
      thiolation were observed in the lung but not in other tissues. Increased contents
      of oxo8dG in DNA were found in all tissues analyzed. When rats were treated with
      buthionine sulfoximine (BSO, 80 mg/kg/day) to deplete glutathione, the oxidative
      effect of cigarette smoking was greatly potentiated. The effect of glutathione
      depletion was most evident in the lung. Cigarette smoking for only 7 days
      resulted in extreme depletion of the glutathione both in the lungs and in the
      liver of BSO-treated rats. Furthermore, oxo8dG in DNA increased markedly,
      especially in lung. The results verified that the lung is a primary target of
      cigarette smoke-induced oxidative damage, and cigarette smoke exerts its
      oxidative effects on the rest of the entire organs eventually. Our results
      indicate that glutathione plays crucial roles in protecting proteins and DNA from
      oxidation caused by cigarette smoking.

PMID- 9655526
TI  - Prevention of reoxygenation injury by sodium salicylate in isolated-perfused rat
      liver.
AB  - Sodium salicylate can be used as a chemical trap for hydroxyl radicals, the most
      damaging reactive oxygen species. Because reactive oxygen species are involved in
      the pathogenesis of hepatic hypoxia/reoxygenation injury, the goal of this study
      was to determine if trapping hydroxyl radicals with salicylate would prevent or
      at least ameliorate such injury. Isolated rat livers, continuously perfused with
      Krebs-Henseleit bicarbonate buffer in the presence or absence of salicylate (2
      mM), were exposed, after 30 min of recovery, to 60 min of hypoxia, followed by 30
      min of reoxygenation. During reoxygenation, control livers experienced a sharp
      increase in the rate of lactic dehydrogenase release, taken as index of cell
      injury, protein carbonyl content, and malondialdehyde, taken as index of protein
      oxidation and lipid peroxidation, respectively. The presence of salicylate in the
      solution perfusion significantly reduced the rate of lactic dehydrogenase
      release, protein carbonyl content, and malondialdehyde production during
      reoxygenation. Hepatic histology documented a significantly reduced cell injury
      in salicylate-perfused livers compared to control livers. These data suggest that
      the hydroxyl radical chemical trap sodium salicylate, acting as an antioxidant,
      may represents an effective agent to reduce liver injury due to
      hypoxia/reoxygenation in a model of isolated-perfused rat liver.

PMID- 9655527
TI  - Reactive oxygen species and DNA oxidation in fetal rat tissues.
AB  - It is well recognized that reactive oxygen species (ROS) are formed during the
      reperfusion of ischemic tissues and ROS may be pathogenic in adult tissues.
      Although there is little information on the formation and toxicity of ROS during
      prenatal life, a strong association has been made between limb and possibly brain
      malformations and uteroplacental ischemia during fetal stages of gestation. It
      has been proposed that these malformations result from attack by ROS formed
      during the resumption of placental perfusion. Studies reported here examined
      formation of ROS in teratogenically sensitive limb and brain and insensitive
      heart before and during the period of teratogenic sensitivity. Also examined was
      the formation of ROS following hypoxia and reoxygenation in fetal culture and DNA
      hydroxylation in sensitive and insensitive fetal tissues during uteroplacental
      ischemia and reperfusion in vivo. Rates of formation of superoxide anion radical
      and hydrogen peroxide declined with increasing gestational age whereas those for
      hydroxyl radical increased. Hydrogen peroxide generation was greatest in
      insensitive heart whereas hydroxyl radical formation was significantly lower in
      brain than in limb or heart, which had comparable rates. Hydrogen peroxide
      generation, which declined significantly in fetuses, but not in membranes with
      gestation, failed to respond to reoxygenation in vitro. Finally, there were
      significant increases in DNA hydroxylation in fetal hearts and limbs, but not in
      brains during uteroplacental ischemia but no further significant change could be
      detected after reperfusion.

PMID- 9655528
TI  - Impairment of the mitochondrial electron chain transport prevents NF-kappa B
      activation by hydrogen peroxide.
AB  - A large body of work has been devoted to mechanisms leading to the activation of
      the transcription factor NF-kappa B in various cell types. Several studies have
      indicated that NF-kappa B activation by numerous stimuli depends on the
      intracellular generation of reactive oxygen species (ROS). In this report, we
      first demonstrated that inhibition of the electron transport chain by either
      rotenone or antimycine A gave rise to dose-dependent inhibition of NF-kappa B
      translocation induced by 150 microM of hydrogen peroxide (H2O2). Conversely, the
      impairment of the mitochondrial respiratory chain did not affect T lymphocyte
      treatment by TNF-alpha (tumor necrosis factor alpha) or pre-B lymphocyte
      treatment with LPS (lipopolysaccharide). We also showed that oligomycine which
      inhibits ATP synthase and FCCP, which uncouples respiration also led to dose
      dependent inhibition of NF-kappa B activation by H2O2. All these inhibitors were
      also shown to inhibit mitochondrial respiration in lymphocytes assessed by oxygen
      consumption. Although only a transient drop in ATP concentration was observed
      when lymphocytes were treated by H2O2, this effect was remarkably reinforced in
      the presence of oligomycine demonstrating the crucial role of ATP in the signal
      transduction pathway induced by H2O2.

PMID- 9655529
TI  - Structure-property relationships of trimetazidine derivatives and model compounds
      as potential antioxidants.
AB  - Twenty-five compounds (trimetazidine derivatives and other compounds, mostly
      having a free phenolic group) were examined for their radical scavenging and
      antioxidant properties. Their reaction with DPPH (2,2-diphenyl-1-picrylhydrazyl)
      as a measure of radical scavenging capacity was assessed by two parameters,
      namely EC50 (the concentration of antioxidant decreasing DPPH by 50%), and log Z,
      a kinetic parameter proposed here and derived from initial second-order rate
      constants and antioxidant/DPPH ratios. Antioxidant activities were determined by
      the inhibition of lipid peroxidation and albumin oxidation. The most active
      compounds were derivatives having a trolox or hydroquinone moiety.
      Physicochemical and structural properties were determined by molecular modeling
      as lipophilicity (virtual log P calculations) and H-Surf (solvent-accessible
      surface of hydroxyl hydrogen) and by quantum mechanical calculations (deltaH(ox)
      = oxidation enthalpy; deltaH(abs) = enthalpy of hydrogen abstraction). QSAR
      models were derived to identify molecular mechanisms responsible for the
      reactivity toward the DPPH radical and for the inhibition of lipid peroxidation.
      A useful prediction of antioxidant capacity could be achieved from calculated
      molecular properties and the kinetic parameter developed here.

PMID- 9655530
TI  - Modification of enzymatic antioxidants in retinal microvascular cells by glucose
      or advanced glycation end products.
AB  - Oxidative stress is one possible pathogenic mechanism to explain diabetic
      microangiopathy. In the present study, we determined the antioxidant enzyme
      activities in bovine retinal microvessels and cultured retinal microvascular
      cells: endothelial cells (BREC) and pericytes (BRP). We further investigated the
      effects of high glucose and advanced glycation end products (AGE) on these enzyme
      activities in BREC and BRP. Antioxidant enzyme activities in native retinal
      microvessels and BREC were quite similar but differed markedly from the BRP ones.
      High glucose decreased Se-GPx activity (about 20%) in BREC compared to mannitol.
      High concentrations of mannitol or NaCl increased Se-GPx activity (up to 40%)
      compared to control medium, suggesting that hyperosmolarity could regulate Se-GPx
      in BREC. No changes in antioxidant enzyme activities were observed when BRP were
      cultured with glucose or mannitol at high concentrations. AGE-BSA had no effect
      on enzyme activities in BREC, whereas 20 microM AGE-BSA increased catalase (40%)
      and superoxide dismutase (60%) activities in BRP. Differences in antioxidant
      enzyme activities observed between BREC and BRP, cultured with high
      concentrations of glucose or AGE, might help to explain their different behavior
      during the pathogenesis of diabetic retinopathy, i.e., early pericyte drop-out
      and late endothelial cell proliferation.

PMID- 9655531
TI  - Retroviruses, ascorbate, and mutations, in the evolution of Homo sapiens.
AB  - Mutations, induced by free radicals, provide a rich molecular palette that other
      evolutionary forces can select for or against. A recent hypothesis proposed that
      large numbers of free radicals were produced when, millions of years ago,
      Anthropoidea lost the ability to produce endogenous ascorbate, increasing the
      frequency of mutations and accelerating the evolution of higher primates.
      Recognizing that retroviruses have been active throughout the period of primate
      evolution, we suggest that an endogenous retrovirus or other retroviral-like
      element may have been involved in mutating the gene coding for gulonolactone
      oxidase (GLO), the terminal step in ascorbate synthesis, approximately 45 million
      years ago. This possibility is supported by the presence of Alu elements (a
      common primate retroelement) adjacent to the site of a missing segment of the
      nonfunctional GLO gene. Although Homo sapiens and other higher primates produce
      other endogenous antioxidants, including superoxide dismutase and uric acid, they
      do not quench the same radicals as ascorbate and cannot fully compensate for a
      lack of endogenous ascorbate. As a consequence, a retrovirus may have played a
      pivotal role in primate and H. sapiens evolution, and the absence of endogenous
      ascorbate may be continuing to accelerate the rate of H. sapiens and primate
      evolution.

PMID- 9655532
TI  - Prospective randomized double blind placebo-controlled evaluation of azithromycin
      for treatment of cat-scratch disease.
AB  - OBJECTIVE: To determine the efficacy of azithromycin in the treatment of patients
      with typical cat-scratch disease. DESIGN: Prospective, randomized, double blind,
      placebo-controlled clinical trial. SETTING: Large military medical center and its
      referring clinics. PATIENTS: Active duty military members and their dependents
      with laboratory-confirmed, clinically typical cat-scratch disease. INTERVENTION:
      Study participants assigned by randomization to treatment with oral azithromycin
      or placebo for 5 days. OUTCOME MEASURES: Lymph node volume was calculated using
      three dimensional ultrasonography at entry and at weekly intervals. The
      ultrasonographer was blinded to the treatment groups. Endpoint evaluations were
      predetermined as time in days to 80% resolution of the initial total lymph node
      volume. RESULTS: Demographic and clinical data showed that the azithromycin and
      placebo treatment groups were comparable at entry although the placebo group
      tended to be older. Eighty percent decrease of initial lymph node volume was
      documented in 7 of 14 azithromycin-treated patients compared with 1 of 15 placebo
      treated controls during the first 30 days of observation (P = 0.026). After 30
      days there was no significant difference in rate or degree of resolution between
      the two groups. CONCLUSIONS: Treatment of patients with typical cat-scratch
      disease with oral azithromycin for five days affords significant clinical benefit
      as measured by total decrease in lymph node volume within the first month of
      treatment.

PMID- 9655533
TI  - Short course therapy with cefuroxime axetil for group A streptococcal
      tonsillopharyngitis in children.
AB  - BACKGROUND: Tonsillopharyngitis caused by group A beta-hemolytic streptococci
      (GABHS) is common in pediatric clinical practice. Standard penicillin therapy may
      be associated with poor compliance, penicillin tolerance in GABHS and microbial
      copathogenicity. Alternative treatments are available (e.g. oral cephalosporins),
      and data suggest that shorter courses of these agents may be effective.
      OBJECTIVE: This open, randomized, multicenter study compared a conventional 10
      day course of the broad spectrum oral cephalosporin, cefuroxime axetil, with a
      shorter 5-day course. METHODS: Cefuroxime axetil suspension, 10 mg/kg, was given
      twice daily to children (ages 3 to 13 years) screened for GABHS
      tonsillopharyngitis. Patients were assessed clinically and bacteriologically 4 to
      7 days after completing the course and followed up at 21 to 28 days. Among 651
      patients recruited 520 had throat cultures positive for GABHS and were randomized
      to treatment. RESULTS: In the 406 patients with microbiologically confirmed GABHS
      infection, eradication of the initial pathogen was recorded in 177 of 201 (88%)
      and 189 of 205 (92%) of patients in the 5- and 10-day groups, respectively, at
      posttreatment. At follow-up, 137 of 162 (85%) of patients in the 5-day group and
      145 of 167 (87%) in the 10-day group maintained bacteriologic eradication. All
      posttreatment isolates of GABHS were susceptible to cefuroxime, and reinfection
      with a different serotype of GABHS was rare (< or =2%) in both groups. The rates
      of recurrence of the pretreatment serotype were 10 and 7% in the 5- and 10-day
      groups, respectively. CONCLUSIONS: Short course therapy with cefuroxime axetil
      suspension may offer an effective alternative treatment to conventional regimens,
      with potential for better compliance and reduced costs.

PMID- 9655534
TI  - Self-reported prescribing of antibiotics for children with undifferentiated acute
      respiratory tract infections with cough.
AB  - BACKGROUND: Physicians are often called on to manage children with acute
      respiratory tract infections with cough when the clinical presentation may not
      allow a differentiation between viral and bacterial etiology. To develop
      guidelines for appropriate antibiotic use, it is necessary to understand the
      present prescribing patterns of physicians who manage children presenting with
      such an undifferentiated acute respiratory tract infection with cough (UARTIC).
      OBJECTIVES: To determine the variability of self-reported prescribing habits for
      antibiotics for children with UARTIC. METHODS: In this cross-sectional survey by
      a modified Dillman's Total Design Method, a mail-out questionnaire was
      administered to a random sample of 181 primary care family physicians and
      pediatricians (Toronto, Ontario, Canada) to assess perceptions of their own
      antibiotic-prescribing habit. RESULTS: Completed questionnaires were received
      from 136 (75%) eligible physicians; 32% reported that > 10% of their office
      visits were for UARTIC. For a 3-day history of UARTIC 24% reported prescribing
      antibiotics or antibiotics in reserve (i.e. a prescription to be filled if the
      patient's condition does not improve) always or most times. This increased to 45%
      when UARTIC had worsened in the 24 h before the office visit (P < 0.001).
      CONCLUSION: When a pediatric patient presented with UARTIC, antibiotics or
      antibiotics in reserve were prescribed in the absence of clear indicators of
      bacterial infection. Research- and evidence-based guidelines are needed to
      support rational antibiotic use for UARTIC.

PMID- 9655535
TI  - Resistance pattern of middle ear fluid isolates in acute otitis media recently
      treated with antibiotics.
AB  - BACKGROUND: Little information is available about the effect of antibiotic
      treatment on the prevalence and MIC of the subsequently isolated pathogens in
      cases of acute otitis media (AOM) failing a course of antibiotic therapy. This
      information is important, particularly regarding the effectiveness of the oral
      antibiotics used in children failing initial therapy. PATIENTS AND METHODS: One
      hundred eighty-one children with culture-positive AOM were prospectively studied
      between October, 1995, and July, 1996. Sixty-three (35%) patients received
      various antibiotics for variable periods during the 14 days preceding enrollment.
      RESULTS: A total of 94 Streptococcus pneumoniae (Pnc) and 113 Haemophilus
      influenzae (Hi) were isolated. Thirty-eight Pnc and 35 Hi were isolated in the 63
      patients with recently treated AOM. Pnc as a single isolate was more prevalent in
      patients recently treated with antibiotics (27 of 63, 43%) than among those not
      recently treated (32 of 118, 27%, P = 0.047). The MIC50 values of penicillin,
      cefaclor and cefuroxime axetil for Pnc were significantly higher in the
      pneumococci isolated from patients recently treated than among those isolated
      from patients not recently treated with antibiotics (0.38, 3 and 0.75 microg/ml
      vs. 0.094, 0.38 and 0.12 microg/ml, respectively). Seventy-nine percent of Pnc
      isolates in the recently treated group had MIC for penicillin of >0.1 microg/ml
      vs. only 47% in those not recently treated (P < 0.05). The respective figures for
      MIC >0.5 microg/ml of cefaclor were 79% vs. 41% for the recently treated and not
      recently treated groups (P < 0.001); cefuroxime MIC >0.5 microg/ml was found in
      61 and 25%, respectively (P = 0.001). CONCLUSIONS: Pneumococcus is more prevalent
      in AOM after a recent antibiotic treatment, and the MIC of the commonly used beta
      lactam drugs for Pnc is considerably higher in this setting. In view of our data,
      the use of oral cephalosporins like cefaclor or cefuroxime as second line drugs
      in the treatment of unresponsive AOM, particularly in regions where resistant PNC
      is prevalent, should be reconsidered.

PMID- 9655536
TI  - Erythromycin resistance of Streptococcus pyogenes in Madrid.
AB  - BACKGROUND: Erythromycin is considered to be an adequate alternative to
      penicillin for patients who are allergic to penicillin. Erythromycin-resistant
      Streptococcus pyogenes strains have been reported in some parts of the world.
      METHOD: The in vitro activity of erythromycin and other antimicrobial agents was
      determined in a total of 1310 clinical Streptococcus pyogenes isolates collected
      in the city of Madrid from January, 1993, through December, 1996. RESULTS: All
      strains showed susceptibility to penicillin, rifampin, vancomycin and
      chloramphenicol. Tetracycline resistance was 8.5%. In 36 of the strains (2.7%)
      MIC was 4 microg/ml for ofloxacin. Clindamycin resistance was observed in only 18
      strains (1.4%); this resistance was constitutive in 15 and inducible in 3
      strains. Resistance to erythromycin was observed in 14.3% of the strains, showing
      an increase during the study period (2.0% in 1993 vs. 22.4% in 1996; chi square
      for linear trend 68.8, P < 0,0001); >90% of them showed the novel resistance
      phenotype described by Seppala et al. and 32 of 32 of these strains showed by PCR
      the 1.4-kb fragment of the mefA gene recently described as the novel macrolide
      efflux resistance determinant. The erythromycin-resistant strains were isolated
      more often in pediatric patients (144 of 872) than in adults (44 of 438) (chi
      square 9.9, P = 0.0016). CONCLUSION: The study emphasizes the need to screen for
      resistance to macrolides in S. pyogenes and indicates that resistance to
      erythromycin in S. pyogenes has increased significantly in Madrid.

PMID- 9655537
TI  - Chlamydia pneumoniae in children attending day-care centers in Gavle, Sweden.
AB  - BACKGROUND: The epidemiology of Chlamydia pneumoniae in healthy children has not
      been established. METHODS: This investigation used polymerase chain reaction
      (PCR) to study the epidemiology of C. pneumoniae in presumed healthy children.
      Four hundred fifty-three children and 142 personnel at 9 day-care centers were
      investigated for carriage of C. pneumoniae. Children found to be positive by PCR
      were also investigated with serology, and their family members were tested with
      PCR. RESULTS: One hundred and three (22.7%) children had a positive PCR, as had
      33 (23.2%) personnel. Fourteen percent of the children younger than 3 years had a
      positive PCR test compared with 26% of the older children (P < 0.01). No
      correlation was found between respiratory symptoms and carriage of C. pneumoniae.
      Mothers were more often positive in the PCR test as compared with fathers
      (relative risk, 2.59; 95% confidence interval, 1.16 to 5.78). Antibodies to C.
      pneumoniae were found in 27 of 97 PCR-positive children; only 2 of whom were
      younger than 3 years. CONCLUSION: C. pneumoniae can be commonly found in young
      children attending day care. Most of the youngest children did not develop
      specific antibodies. Children may have subclinical infections with C. pneumoniae.
      The organism seems to be easily communicable among individuals living in close
      proximity.

PMID- 9655538
TI  - Cerebrospinal fluid profile in patients with acute Kawasaki disease.
AB  - BACKGROUND: Kawasaki disease (KD) is an acute vasculitis of infancy and early
      childhood for which there is currently no diagnostic test. The clinical
      presentation of KD may initially resemble other infectious diseases, including
      bacterial or viral meningitis. For this reason lumbar puncture (LP) is sometimes
      performed during the evaluation of these patients. To understand the range of
      cerebrospinal fluid (CSF) changes that may be associated with acute KD, a
      retrospective review of unselected KD patients from three pediatric centers was
      performed. METHODS: Retrospective chart review was performed on KD patients
      evaluated during the first 10 days of illness who had an LP performed before the
      administration of intravenous gamma-globulin. RESULTS: During the 6.5-year study
      period, 46 KD patients underwent LP as part of their clinical evaluation. Of
      these patients 18 (39.1%) had CSF pleocytosis, 1 (2.2%) had a CSF glucose <45
      mg/dl and 8 (17.4%) had an elevated CSF protein. Of the patients with CSF
      pleocytosis, the median white blood cell count was 22.5 cells (range, 7 to 320
      cells), with a median of 6.0% neutrophils (range, 0 to 79%) and 91.5% mononuclear
      cells (range, 11 to 100%). CONCLUSIONS: In the present series approximately one
      third of KD patients who underwent an LP had CSF pleocytosis with a mononuclear
      cell predominance. No patient had significant hypoglycorrhachia, and elevation of
      the CSF protein was uncommon. CSF abnormalities were similar between US and
      Japanese KD patients. The basis for the CSF pleocytosis in acute KD patients
      remains unknown.

PMID- 9655539
TI  - Prevalence of intestinal infections caused by diarrheagenic Escherichia coli in
      Bedouin infants and young children in Southern Israel.
AB  - OBJECTIVE: To evaluate the prevalence of different Escherichia coli categories in
      symptomatic and asymptomatic infants and children residing in a Bedouin township
      in Southern Israel. METHODS: A total of 1613 stool samples were collected from a
      cohort of 234 infants and young children followed from birth up to 2 years of
      age. E. coli colonies from stool cultures from children during a diarrhea episode
      and those from nondiarrhea stools were hybridized with DNA probes specific for
      enteropathogenic, enteroinvasive, enterotoxigenic (ETEC), enteroaggregative,
      diffuse adherent and enterohemorrhagic strains. RESULTS: There were 1469 of 1613
      (91%) samples positive for E. coli. The prevalence of E. coli categories was:
      enteroaggregative (25.9%); diffuse adherent (21.8%), ETEC (12.9%);
      enteropathogenic (7.3%); enterohemorrhagic (0.5%); and enteroinvasive (0.2%).
      ETEC, expressing the heat-stable enterotoxin (ST), was the only category isolated
      significantly more often from cases than from controls (P = 0.005). Of the two
      heat-stable enterotoxins screened in this study, only ETEC-heat stable
      enterotoxin (STh), the form isolated from human pathogenic ETEC, could be
      associated with diarrhea, whereas ETEC-STp, produced by ETEC of porcine origin,
      was not related to diarrhea. ETEC infections peaked during the warm, dry season.
      Prolonged shedding of E. coli postdiarrhea was not found in this population.
      CONCLUSION: The present cohort study confirmed that in this semiurban area,
      highly endemic for diarrheal disease, ETEC is an important cause of diarrhea in
      children.

PMID- 9655540
TI  - Serologic and virologic evidence for frequent intrauterine transmission of human
      parvovirus B19 with a primary maternal infection during pregnancy.
AB  - OBJECTIVE: To define the intrauterine viral transmission rate during primary
      maternal parvovirus B19 infection and identify factors that may influence this
      rate. METHODS: Forty-three pregnant women at two medical centers were identified
      with a primary B19 infection and followed to delivery. At delivery maternal and
      infant (umbilical cord) blood was obtained for B19 serologic and virologic PCR
      testing. RESULTS: All of the women delivered healthy infants at term and none was
      hydropic. Overall 22 (51%) of the 43 infants had some evidence of a congenital
      B19 infection. B19-specific IgM was detected in 11 infants at delivery, B19 IgA
      was detected in 10 and B19 DNA was detectable by PCR in 11 infants. One infant
      was negative at birth but became positive for IgM, IgA and PCR at 6 weeks of age.
      No association was found between the likelihood of intrauterine infection and:
      maternal age; symptomatic maternal infection; method of delivery; maternal IgG
      titer at delivery; maternal IgG avidity at delivery; or maternal viremia at
      delivery. Intrauterine infection was associated with maternal IgM positivity at
      delivery; this association may have been a result of maternal infection occurring
      later in gestation. CONCLUSION: Although the incidence of intrauterine hydrops
      and fetal demise after maternal infection is low, there is a high rate of
      intrauterine viral infection that occurs throughout gestation and yields newborns
      who, although infected in utero, are asymptomatic at birth.

PMID- 9655541
TI  - Comparison of two antiretroviral triple combinations including the protease
      inhibitor indinavir in children infected with human immunodeficiency virus.
AB  - OBJECTIVE: The effects of two antiretroviral triple combinations including the
      protease inhibitor indinavir on the surrogate markers, viral load and CD4 cells
      were evaluated. METHODS: Fifteen patients with high viral load or disease
      progression under their prior antiretroviral therapy were switched to
      zidovudine/lamivudine/indinavir (Group A, n = 10) or
      stavudine/lamivudine/indinavir (Group B, n = 5). Serial determinations of viral
      load and CD4 cells were performed. RESULTS: The median reduction of the viral
      load was 0.6 log after 3 months and 0.8 log after 6 months in Group A and 2.5 and
      2.4 log after 3 and 6 months in Group B, respectively. After 3 and 6 months 3 of
      10 patients in Group A and 3 of 5 patients in Group B had viral load reductions
      below the detection limit of the assay. Patients with an additional switch of
      nucleoside analogues at start of indinavir therapy (regardless of the specific
      reverse transcriptase inhibitor used) had significantly better reductions of the
      viral load than patients without such a switch (median 2.3 log vs. 0.2 log after
      6 months, P < 0.05). In Group A the median of the relative increase of CD4 cells
      was 37% after 3 months and 57% after 6 months (P = 0.002); in Group B the medians
      of the relative increase of CD4 cells were 145 and 163% (not significant),
      respectively. Two patients from Group A and 1 from Group B developed renal
      calculi, which resolved after adequate hydration. One patient was withdrawn
      because of intractable vomiting attributed to indinavir. CONCLUSION: In a small
      cohort of HIV-infected pediatric patients with extensive prior antiretroviral
      treatment, triple therapy including indinavir had a sustained effect on the
      decrease of the viral load and the increase of CD4 cells similar to results
      obtained in antiretrovirally experienced adults. This effect was significantly
      better in patients with an additional switch of a nucleoside analogue at start of
      triple therapy with indinavir than in patients without such a change.

PMID- 9655542
TI  - Maternal carriage of group B streptococci in developing countries.
AB  - BACKGROUND: Group B streptococcus (GBS) is a leading cause of neonatal sepsis in
      many industrialized countries, but reports from the developing world infrequently
      identify this pathogen among newborns with sepsis. Studies of GBS colonization
      among women living in developing countries were reviewed to determine whether
      lower colonization rates might account for these findings. METHODS: Literature
      was reviewed with the use of Medline Express (1980 to 1996) and Abstracts on
      Tropical Agriculture and Rural Development in the Tropics (1975 to 1995). The
      methods of each report were considered adequate if specimens were collected from
      the vagina and if selective broth media were used. RESULTS: Thirty-four studies
      reported results of cultures from 7730 women; overall colonization was 12.7%.
      Among only those studies in which methods were adequate, 17.8% (675 of 3801)
      women were identified as colonized. Studies with adequate methods found
      significantly higher colonization rates (relative risk, 2.3; 95% confidence
      interval, 2.0 to 2.6) than those using inadequate methods. When analysis was
      restricted to reports with adequate methods, the prevalence of colonization by
      region was as follows: Middle East/North Africa, 22%; Asia/Pacific, 19%; Sub
      Saharan Africa, 19%; India/Pakistan, 12%; and Americas, 14%. CONCLUSION: Although
      there is significant geographic variation in the proportion of women colonized
      with GBS, the range of colonization reported from developing countries is similar
      to that identified in populations studied in the United States. Specimen
      collection and microbiologic methods are important factors in identification of
      women colonized with GBS.

PMID- 9655543
TI  - Candidemia in a neonatal intensive care unit: trends during fifteen years and
      clinical features of 111 cases.
AB  - OBJECTIVE: To determine changes in the incidence of candidemia in a neonatal
      intensive care unit (NICU) during a 15-year period (1981 to 1995) and to compare
      the prevalence and case fatality rates of Candida albicans and Candida
      parapsilosis infections. METHODS: A retrospective study was conducted of
      candidemia occurring in infants in a NICU between January 1, 1981, and December
      31, 1995. Cases were identified through computerized searching of a microbiology
      blood culture database. Candidemia was considered contributory to mortality if
      death occurred within 3 days of positive blood cultures or if there was autopsy
      evidence of disseminated candidiasis. RESULTS: One hundred eleven cases of
      candidemia occurred in 107 infants, representing 1% of all NICU patients during
      the study period. The rate of candidemia in the NICU increased from 2.5 cases per
      1000 admissions in 1981 to 1985, to 4.6 per 1000 admissions in 1986 to 1990 and
      to 28.5 per 1000 in 1991 to 1995 (P = 0.001). C. albicans was the predominant
      cause of candidemia between 1981 and 1990. C. parapsilosis was the most prevalent
      species between 1991 and 1995, causing 53 of 89 cases (60%). The mortality from
      C. albicans, 13 of 50 cases (26%), was significantly higher than the mortality
      from C. parapsilosis, 2 of 54 (4%) (P = 0.002; relative risk, 7; 95% confidence
      interval, 1.7 to 30). CONCLUSIONS: The rate of candidemia in our neonatal
      intensive care unit increased >11-fold in the 15 years from 1981 to 1995; the
      prevalent Candida species shifted from C. albicans to C. parapsilosis; and
      candidemia associated with C. albicans has significantly higher mortality than
      with C. parapsilosis.

PMID- 9655544
TI  - Multiresistant Pseudomonas aeruginosa outbreak in a pediatric oncology ward
      related to bath toys.
AB  - BACKGROUND: Nosocomial outbreaks of Pseudomonas aeruginosa in pediatric hospitals
      frequently involve neonates and immunosuppressed patients and can cause
      significant morbidity and mortality. OBJECTIVE: To describe the investigation of
      a multidrug-resistant P. aeruginosa outbreak in a pediatric oncology ward at the
      Royal Children's Hospital, Melbourne, Australia. DESIGN AND METHODS: Specimens
      were collected from infected patients and the ward environment. Bacterial
      isolates were characterized by antibiotic susceptibility patterns and bacterial
      DNA fingerprinting performed by pulsed-field gel electrophoresis (PFGE). A case
      control study was carried out to assess possible risk factors for infection.
      RESULTS: Eight patients had clinical illnesses including bacteremia (n = 5) and
      infections of skin (n = 2), central venous catheter site (n = 1) and urinary
      tract (n = 1). The environmental ward survey yielded isolates of multiresistant
      P. aeruginosa from a toy box containing water-retaining bath toys, as well as
      from three of these toys. Pulsed-field gel electrophoresis of bacterial DNA
      demonstrated identical band patterns of the isolates from patients, toys and toy
      box water. A case-control study involving the 8 cases and 24 disease-matched
      controls demonstrated a significant association between P. aeruginosa infection
      and use of bath toys (P = 0.004), use of bubble bath (P = 0.014), duration of
      stay (P = 0.007) and previous antibiotic exposure (P = 0.026). Cultures from the
      bubble bath liquid were negative. CONCLUSION: This is the first description of a
      nosocomial outbreak associated with toys. We caution against the use of water
      retaining bath toys in wards treating immunocompromised children.

PMID- 9655545
TI  - Combination antiretroviral therapy.

PMID- 9655546
TI  - Clarithromycin and azithromycin.

PMID- 9655547
TI  - Infectious diseases in internationally adopted children: the past five years.

PMID- 9655549
TI  - Comparison of oral erythromycin, local administration of streptomycin and placebo
      therapy for nonsuppurative Bacillus Calmette-Guerin lymphadenitis.

PMID- 9655548
TI  - Central nervous system tuberculosis after resolution of miliary tuberculosis.

PMID- 9655550
TI  - Relationship between unsupplemented vitamin A serum concentrations and measles
      vaccine response in Jamaican children.

PMID- 9655551
TI  - Primary human immunodeficiency virus type 1 infection during pregnancy associated
      with transmission of SI/MT-2 cell tropic virus and precipitous loss of CD4 cells
      in mother and infant.

PMID- 9655552
TI  - Streptococcus pneumoniae-associated hemolytic uremic syndrome.

PMID- 9655553
TI  - Infection control for neonatal gram-negative bacterial infections.

PMID- 9655554
TI  - Swabbing computers in search of nosocomial bacteria.

PMID- 9655555
TI  - Raw beef consumption and improper use of chopsticks as a possible cause of
      Escherichia coli O157 infection in Japan.

PMID- 9655557
TI  - Otoscopy for the diagnosis of otitis media.

PMID- 9655558
TI  - Use of tympanometry in office practice for diagnosis of otitis media.

PMID- 9655559
TI  - Acoustic reflectometry: spectral gradient analysis for improved detection of
      middle ear effusion in children.

PMID- 9655560
TI  - Comparison of spectral gradient acoustic reflectometry and other diagnostic
      techniques for detection of middle ear effusion in children with middle ear
      disease.

PMID- 9655561
TI  - Spectral gradient acoustic reflectometry for the detection of middle ear effusion
      by pediatricians and parents.

PMID- 9655562
TI  - Implications of pharmacokinetics in making choices for the management of acute
      otitis media.

PMID- 9655563
TI  - Protecting the therapeutic advantage of antimicrobial agents used for otitis
      media.

PMID- 9655564
TI  - Treatment of acute otitis media in an era of increasing microbial resistance.

PMID- 9655565
TI  - Current recommendations for initial therapy in hypertension: are they still
      valid? Introduction.
AB  - This symposium will address questions regarding current recommendations for
      initial therapy in the management of hypertension: Are we treating too many
      hypertensive patients or too few? When do we start treatment with medications and
      what medications should we use? Professor Lawrence Ramsay from England will
      discuss the concept of absolute versus relative risk and review the long-term
      hypertension treatment trials and what they have and have not told us. Dr.
      Michael Weber of New York will discuss some newer data on angiotensin converting
      enzyme inhibitors, angiotensin II receptor antagonists, and calcium channel
      blockers and attempt to answer the question: are these data sufficient to warrant
      recommending these agents as initial therapy? Finally, Dr. Henry Black of Chicago
      and I will update a new-old concept: is it time to consider low-dose fixed
      combination therapy as initial treatment in hypertension?

PMID- 9655566
TI  - The role of combination therapy in the treatment of hypertension.
AB  - Only approximately 40% to 50% of hypertensive patients will achieve goal blood
      pressures of <140/ 90 mm Hg with monotherapy, regardless of the medication used.
      Fixed-dose combination therapy with two different classes of antihypertensive
      agents will achieve goal pressures in more than 70%. The sixth Joint National
      Committee on Detection, Evaluation, and Treatment of High Blood Pressure has
      suggested that the use of combination therapy is appropriate as initial
      treatment. The advantages of combinations include: 1) greater blood pressure
      decrease and response rates than monotherapy; 2) fewer side effects with small
      doses of two drugs than with large doses of one agent; 3) improved adherence to
      treatment; and 4) possibly lower cost of therapy. Many different combinations of
      diuretics and beta-blockers, angiotensin converting enzyme (ACE) inhibitors and
      angiotensin II receptor antagonists, as well as ACE inhibitors and calcium
      antagonists are available. Two of these, Ziac and Capozide, have been approved as
      initial therapy. It is possible that the number of hypertensive individuals
      controlled at goal blood pressure levels will be increased if combination therapy
      is used as initial treatment.

PMID- 9655567
TI  - The rationale for differing national recommendations for the treatment of
      hypertension.
AB  - This article examines the rationale for the differences in the guidelines for
      hypertension management of four national or international bodies: the Joint
      National Committee (JNC-V), The World Health Organization/International Society
      of Hypertension (WHO-ISH), the British Hypertension Society (BHS), and the New
      Zealand guidelines. These guidelines agree on many aspects of management, but
      differ on two very important points-the drugs of first choice for hypertension,
      and the indications for drug treatment of uncomplicated mild hypertension. JNC-V
      recommends treatment routinely of all people with a sustained blood pressure of
      140/90 mm Hg, whereas the BHS guidelines advise treatment routinely at 160/100 mm
      Hg. Such differences in the threshold for treatment have a major impact on the
      proportion of the adult population to be treated, and on the benefit from
      treatment. JNC-V was heavily influenced by the Hypertension Detection and Follow
      up Program (HDFP), which appeared to show a large benefit from the treatment of
      uncomplicated mild hypertension, whereas the BHS guidelines were influenced by
      the Medical Research Council (MRC) Trial, which showed a very small benefit.
      However, the apparent differences in absolute benefit between these, and other,
      randomized controlled trials is related entirely to differences in the absolute
      cardiovascular risk of the populations studied. In populations and in individual
      patients the benefit from antihypertensive treatment is determined by the
      absolute cardiovascular risk. Blood pressure by itself is a very weak predictor
      of risk or benefit from treatment. In uncomplicated mild hypertension the need
      for drug therapy should be based on the absolute risk of cardiovascular
      complications, estimated by considering age, sex, serum cholesterol level,
      diabetes mellitus status, and smoking habits, in addition to blood pressure.
      Doctors cannot estimate absolute risk accurately informally or intuitively, and
      the next generation of guidelines should incorporate a simple but accurate method
      for estimating cardiovascular risk, similar to that in the New Zealand
      guidelines. The decision to treat, or not treat, uncomplicated mild hypertension
      should be based on a formal estimate of absolute cardiovascular risk and not on
      an arbitrary blood pressure threshold. As regards drugs of first choice, the
      available evidence supports strongly the stance of JNC-V and JNC VI that
      diuretics and beta-blockers should be preferred unless they are contraindicated,
      or unless there are positive indications for other drug classes.

PMID- 9655568
TI  - Translating data on antihypertensive drugs into clinical practice.
AB  - Two problems in the treatment of hypertension continue to be largely unsolved.
      The first, and more simple, is our inability to adequately control blood pressure
      in the majority of hypertensive patients. This not only reflects the difficulty
      of retaining patients in effective treatment programs, but also of convincing
      physicians to strive for optimal blood pressure levels. There is a continuing
      need for new antihypertensive drugs and combinations to help accomplish these
      goals. The second major problem is that the major clinical endpoints, including
      coronary events and renal failure, have not been adequately reduced by
      traditional therapies. Standard regimens, particularly those including diuretics,
      have protected against strokes and heart failure. Our improved understanding of
      vascular biology in hypertension has directed interest to the mechanisms in
      hypertensive patients that might accelerate atherosclerosis and vascular events
      in these individuals. This involves addressing the concomitant metabolic risk
      factors that comprise the "Hypertension Syndrome," and, perhaps of equal
      importance, finding therapies that directly inhibit unwanted types of growth and
      proliferative activities within the walls of critical arteries. Many substances
      within the endothelium and the vascular wall may participate as initiators or
      mediators of pathology, but most information thus far has focused on the renin
      angiotensin system. Angiotensin converting enzyme inhibitors (and potentially
      angiotensin receptor blockers) have provided coronary and renal protection in
      various cardiovascular conditions, though not yet in formal hypertension trials.
      Calcium channel blockers have also shown promise, including recent stroke and
      cardiovascular benefits in patients with isolated systolic hypertension, but,
      again, definitive coronary data in hypertension are awaited. Unless concomitant
      conditions mandate the selection of a particular antihypertensive drug class,
      physicians currently have a dilemma: should they choose drugs from older classes
      that have not provided full protection? Or, should they prescribe newer agents
      with exciting potential but with, as yet, unproved endpoint benefits in
      hypertension? Until currently ongoing prospective trials of antihypertensive
      therapy are completed, physicians must be guided by their own interpretations of
      the available data.

PMID- 9655569
TI  - Reproductive performance, calf growth, and milk production of first-calf heifers
      sired by seven breeds and raised on different levels of nutrition.
AB  - We evaluated heifers crossbred from seven breeds of sires (Hereford, Angus,
      Belgian Blue, Piedmontese, Brahman, Boran, and Tuli) and three breeds of dams
      (Angus, Hereford, and MARC III [four-breed composite]). Heifers were mated to Red
      Poll sires to calve at 2 yr of age. Heifers were placed in two treatments from
      weaning to breeding and raised on a high nutrition level (15.8 Mcal ME/d) or on
      80% of the high nutrition level (12.6 Mcal ME/d). Breeds differed in the age of
      the heifers at parturition (P = .03). Birth weights of calves differed by
      maternal grandsire (P < .001) but not by heifer treatment (P = .91) or maternal
      grandam (P = .19). Heifers differed in their postpartum interval to estrus by
      sire breed (P = .001). Calf age at weaning (P = .02), calf ADG (P < .001), and
      205-d weight (P < .001) differed between breeds of maternal grandsires. Milk
      production from 50 to 200 d of lactation was greatest for heifers of Belgian Blue
      (1,070 +/- 30 kg) and Brahman (1,029 +/- 38 kg) sires. Milk production did not
      differ with treatment group (P = .84). This study suggests that over a diverse
      group of breeds, accelerated rates of gain during the postweaning period within
      the ranges of this study do not result in increased production efficiency of the
      cows.

PMID- 9655570
TI  - Pregnancy rates of postpartum beef cows that were synchronized using Syncro-Mate
      B or the Ovsynch protocol.
AB  - We compared pregnancy rates of beef cows subjected to the traditional Syncro-Mate
      B protocol or the new Ovsynch protocol and timed insemination. Multiparous Angus
      cows (n = 436) were stratified by age, postpartum interval, and AI sire and were
      randomly divided into two treatment groups for synchronization of
      estrus/ovulation. Approximately half of the cows (n = 216) received the
      traditional Syncro-Mate-B protocol with 48-h calf removal from the time of
      implant removal until breeding. The remaining cows (n = 220) received the Ovsynch
      protocol, which consists of an injection of GnRH (100 microg) on d -10, an
      injection of PGF2alpha (25 mg) and 48-h calf removal on d -3, another injection
      of GnRH and calf return on d -1, and timed insemination 24 h later (d 0). Blood
      samples were collected from all cows before treatment to identify anestrous and
      cyclic females. Pregnancy rates were higher (P < .025) for Ovsynch-treated cows
      (54%) than for Syncro-Mate-B-treated cows (42%). Pregnancy rates of cyclic
      Ovsynch-treated cows (59%) were higher (P < .005) than pregnancy rates of cyclic
      Syncro-Mate-B-treated cows (38%). Pregnancy rates of anestrous cows also tended
      to favor synchronization with the Ovsynch protocol. From these data, we conclude
      that the Ovsynch protocol is capable of inducing a fertile ovulation in cyclic
      and anestrous beef cows and that pregnancy rates to a timed insemination are
      higher than those obtained with synchronization of estrus using Syncro-Mate-B.

PMID- 9655571
TI  - Sex effects on breed of sire differences for birth, weaning, and yearling
      weights.
AB  - Weights of males and females can be considered to be correlated traits with
      different averages and variances. This study attempted to determine whether
      defining traits as expressed in males or in females would change estimates of
      breed of sire differences needed to calculate across-breed factors for adjustment
      of within-breed EPD to across-breed EPD. Records from the US Meat Animal Research
      Center of progeny of Hereford, Angus, and MARC III composite dams mated to 12
      sire breeds that had been used to calculate breed of sire adjustments in 1996
      were used. Breeds of sire were Hereford, Angus, Shorthorn, Brahman, Simmental,
      Limousin, Charolais, Maine-Anjou, Gelbvieh, Pinzgauer, Tarentaise, and Salers.
      Female and male records for birth (BWT), weaning (WWT), and yearling (YWT)
      weights were considered to be separate although correlated traits. Heritability
      estimates for expression as females and males were as follows: .44 and .47 for
      BWT, .25 and .19 for WWT, and .55 and .49 for YWT. Corresponding genetic
      correlations between expression in males and females were .85, 1.00, and .92.
      Phenotypic standard deviations were slightly larger and coefficients of variation
      slightly smaller for males than for females; the largest differences were for
      YWT. Breeds ranked similarly for female and male weights; the major exception was
      Brahman for BWT. Averages of breed of sire contrasts for expression in females
      and males were almost identical to contrasts from analyses of combined male and
      female records. Largest differences between averaged and combined breed of sire
      contrasts were approximately 1 kg for BWT and WWT and approximately 2 kg for YWT.
      The results show that considering male and female weights as separate traits is
      not needed in calculation of across-breed adjustment factors from US Meat Animal
      Research Center records.

PMID- 9655572
TI  - Technical note: Detection of bovine kappa-casein variants A, B, C, and E by means
      of polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP).
AB  - We used polymerase chain reaction-single strand conformation polymorphism (PCR
      SSCP) analysis to screen the most frequent variants (A, B, C, and E) found in the
      bovine kappa-casein gene. The PCR products (453 bp) were heat-denatured, loaded
      onto nondenaturing polyacrylamide gels, and silver-stained. Each variant yielded
      patterns clearly distinguishable from the others. Optimal conditions for the
      simultaneous detection of the four variants were 12% polyacrylamide gels (100:1
      acrylamide:bis-acrylamide ratio) with 5% glycerol and a constant running
      temperature of 10 degrees C. Eight reference samples initially used for this
      purpose and 40 anonymous samples of different cattle breeds diagnosed by PCR-RFLP
      and PCR-SSCP showed no discrepancies between the two methods and confirmed
      previous results. Because it is cost-effective, sensitive, and fast, PCR-SSCP is
      strongly recommended to routinely screen kappa-casein variants for industrial
      purposes or in cattle selection schemes.

PMID- 9655573
TI  - Additive and nonadditive genetic variability for growth traits in the Turipana
      Romosinuano-Zebu multibreed herd.
AB  - Intrabreed additive genetic, environmental, and phenotypic variances and
      covariances for Romosinuano (R) and Zebu (Z), as well as interbreed nonadditive
      genetic variances and covariances (sire x breed-group-of-dam interactions), for
      birth weight (BWT), weaning weight (WW), and postweaning gain (GW) were computed
      using a Romosinuano-Zebu multibreed data set from the Turipana Experiment Station
      in Colombia. Covariances were estimated with a sire-maternal grandsire model,
      using a multibreed REML procedure. The computing algorithm was a generalized
      expectation-maximization (GEM) algorithm. This algorithm yields no asymptotic
      standard errors as part of its computations. Because of the small size of the
      data set (2,546 calves), these REML covariance estimates should be viewed with
      caution. Estimates of intrabreed heritabilities were similar to the ratios of
      interbreed nonadditive to phenotypic variances (interactibilities) for direct and
      maternal effects of the growth traits evaluated in this study. Intrabreed
      heritability estimates for BWT, WW, and GW direct genetic effects were .16, .09,
      and .14, for R and .24, .10, and .14 for Z. Corresponding heritability values for
      maternal effects were .18, .09, and .23 for R and .14, .13, and .07 for Z.
      Interactibility estimates were .21, .05, and .12, for direct and .26, .04, and
      .11, for maternal BWT, WW, and GW. Negative correlations between additive
      maternal weaning weight and direct and maternal postweaning gain, as well as
      between environmental weaning weight and postweaning gain, suggested that there
      was compensatory postweaning gain in this herd. Estimates of genetic variation
      and predictions of expected progeny differences showed that Romosinuano animals
      competed well against Zebu and RZ crossbred animals under the tropical
      environmental conditions at Turipana.

PMID- 9655574
TI  - Survival, body weights, feed efficiency, and carcass traits of 7/8 White
      Composite and 1/8 Duroc, 1/8 Meishan, 1/8 Fengjing, or 1/8 Minzhu pigs.
AB  - Pigs were the progeny of White Composite boars mated to gilts that were either
      1/4 Duroc, 1/4 Meishan, 1/4 Fengjing, or 1/4 Minzhu and the remainder 3/4 White
      Composite. One-eighth Meishan and 1/8 Fengjing pigs averaged approximately .5
      more nipples than 1/8 Duroc pigs and .2 more nipples than 1/8 Minzhu pigs (P <
      .05), respectively. Duroc, Meishan, and Minzhu crosses did not differ (P > .05)
      for survival at birth or at 14 and 28 d. Fengjing crosses had a lower survival
      rate (P < .05) at all three ages than Duroc and Meishan crosses. Duroc crosses
      were heavier (P < .05) than Chinese crosses at birth. At 56 d, Duroc and Meishan
      crosses did not differ (P > .05) for BW, but both were heavier (P < .05) than
      Minzhu crosses. Body weight at 70 d did not differ significantly (P > .05) among
      breed types. Duroc crosses were heavier (P < .05) than any of the Chinese crosses
      at 98, 126, and 154 d of age. At 154 d, Fengjing crosses were lighter (P < .05)
      than Meishan or Minzhu crosses. The effect of breed type was not detected for
      average probe backfat thickness of gilts at 99.7 kg. Duroc crosses consumed the
      most feed, and Fengjing crosses consumed the least during each interval and
      during the total period (P < .05). Feed consumption of Meishan and Minzhu crosses
      was intermediate to and significantly (P < .05) different from that of Duroc and
      Fengjing crosses. At 184 d of age, breed types did not differ (P > .16) for
      measures of carcass fat thickness, marbling score, color score, and firmness
      score. At 184 d of age, weights of all carcass cuts were heavier (P < .05) for
      Duroc than for Chinese crosses with the exception of untrimmed loin weight of
      Minzhu crosses. There were few significant differences among breed types when
      carcass traits were compared at a constant carcass weight, although Duroc crosses
      generally were superior. Relative to similar Duroc crosses, these results suggest
      that 1/8 Chinese pigs would grow less rapidly (P < .05) and produce less weight
      of trimmed lean cuts at a constant carcass weight.

PMID- 9655575
TI  - Reproduction of 3/4 White Composite and 1/4 Duroc, 1/4 Meishan, 1/4 Fengjing, or
      1/4 Minzhu gilts and sows.
AB  - Females were either 1/4 Duroc, 1/4 Meishan, 1/4 Fengjing, or 1/4 Minzhu, and the
      remainder were 3/4 White Composite. A greater percentage of Fengjing crosses
      reached puberty than Duroc or Minzhu (P < .05), and Meishan crosses were
      intermediate and not different (P > .05) from other breed types. After adjusting
      for differences in percentage detected owing to termination of observation for
      estrus, breed types ranked Fengjing, Meishan, Minzhu, and Duroc from youngest to
      oldest at puberty with approximately 14 d between adjacent breed types. Meishan
      and Fengjing crosses had a greater (P < .05) ovulation rate than Minzhu or Duroc
      crosses. With the exception of number of fetuses at 100 d and average fetal
      weight at 60 d, differences among breed types were not detected (P > .05) for
      litter or uterine traits measured on gilts slaughtered at 60 or 100 d of
      gestation. Total number of pigs born was greater (P < .05) for 1/4 Fengjing than
      for 1/4 Duroc gilts. Gestation length, number born alive, number weaned, litter
      birth weight, or litter weaning weight for gilts did not differ (P > .05) among
      breed types. Duroc crosses were heavier (P < .01) than Chinese crosses at d 1 and
      28 after farrowing, but breed types did not differ (P > .05) for backfat
      thickness at those times. Breed types did not differ (P > .05) for the ratio of
      litter gain from 0 to 28 d/total Mcal or any of the component traits in the
      ratio. Postweaning estrus activity, conception rate, and litter and uterine
      traits of sows bred for second parity were not affected (P > .05) by breed type.
      These analyses indicate that crossbred gilts containing 1/4 Meishan, 1/4
      Fengjing, or 1/4 Minzhu will reach puberty earlier, have larger litters, and
      weigh less at first parity than gilts containing 1/4 Duroc, but they do not have
      any significant advantage in litter size at second parity.

PMID- 9655576
TI  - Heat tolerance in Tuli-, Senepol-, and Brahman-sired F1 Angus heifers in Florida.
AB  - We investigated heat tolerance and growth rate in two trials under ambient
      conditions in central Florida. Trial 1 (1994) involved 38 Brahman (B), 21 Senepol
      (S), 19 B x Angus (A), 20 S x A, and 20 Tuli (T) x A heifers. Trial 2 (1995)
      involved 13 A, 35 B, 30 S, 23 B x A, 17 S x A, and 28 T x A heifers. Measurements
      were made on three consecutive weeks during the hotter and cooler seasons of each
      year and included rectal temperature (RT, degrees C), respiration rate (RR, bpm),
      temperament score (TS; 1 = very docile, 5 = very aggressive), blood packed-cell
      volume (PCV), and plasma cortisol concentration (CORT). Data for RT were
      transformed (log10 [RT - 37]) before analysis. On the hottest date in Trial 1,
      log10 RT was not different between B (.39 +/- .011) and B x A (.37 +/- .016) or
      between T x A (.35 +/- .015) and B x A, but log10 RT was lower (P < .05) in S x A
      (.30 +/- .015) than in either S (.35 +/- .015) or T x A. On all dates in Trial 1,
      RR was lower (P < .05 to .001) and PCV was higher (P < .05 to .001) in B than in
      B x A. There were few differences in TS except on two dates when B scored higher
      (P < .01 to .001) than B x A, and these differences were associated with higher
      (P < .05) CORT in B than in B x A. Using initial BW as a covariate, adjusted ADG
      (kg) of T x A (.52 +/- .023) was not different from adjusted ADG of B x A (.57 +/
      .024) or S x A (.54 +/- .023). On the hottest date in Trial 2, log10 RT and RR
      were higher (P < .001) in A (.59 +/- .017, 74 +/- 2.7) than in B (.47 +/- .010,
      39 +/- 1.6), S (.42 +/- .011, 50 +/- 1.8), and crossbred heifers (.47 +/- .011,
      60 +/- 1.8; .43 +/- .014, 55 +/- 2.4; and .50 +/- .012, 48 +/- 2.0 for T x A, S x
      A and B x A, respectively), and RR was higher (P < .001) in B x A than in B. On
      the coolest date in Trial 2, RR was slightly lower in B (32 +/- .5) than in A(34
      +/- .7, P < .01) and B x A (36 +/- .6, P < .001) and was associated with higher
      PCV in B than in A. On both dates, TS and CORT were higher (P < .01) in B than in
      A. In Trial 2, adjusted ADG (kg) was higher (P < .01) in B (.43 +/- .017) than in
      A (.32 +/- .033), higher (P < .001) in S (.45 +/- .018) than in A, and higher (P
      < .001) in crossbreds (B x A [.53 +/- .023] + S x A [.44 +/- .025] + T x A [.46
      +/- .019]) than in A. These data indicate that heat tolerance in F1 crosses of
      tropically adapted breeds (Tuli, Senepol, Brahman) with a temperate breed (Angus)
      is similar to heat tolerance displayed by purebred tropical breeds (Senepol,
      Brahman).

PMID- 9655577
TI  - Eating barley too frequently or in excess decreases lambs' preference for barley
      but sodium bicarbonate and lasalocid attenuate the response.
AB  - We conducted experiments to determine whether preference for barley was affected
      when lambs ate various amounts of barley and whether lambs ate more barley when
      it contained lasalocid and sodium bicarbonate (NaHCO3), both of which attenuate
      acidosis. In Exp. 1, lambs were assigned to two treatments (six lambs/treatment).
      For 2 d, lambs in two treatments were offered either 400 or 1,200 g of rolled
      barley from 0600 to 0700 as a preload meal. A preference ratio [PR = barley
      ingested/(total amount of alfalfa + barley ingested)] was calculated based on
      lambs' intake when offered a choice of 200 g each of rolled barley and alfalfa
      pellets hourly from 0700 to 1100. After the preload meal, lambs in Treatment 1
      (400 g preload) showed equal preference for barley (.52) and alfalfa (.48) for 4
      h on d 1 (P > .05); their preference for barley was less after the meal of barley
      on d 1 (.52) than on d 2 (.72), but their preference for barley declined between
      h 3 (.81) and 4 (.55) of d 2 (P = .11). Lambs in Treatment 2 (1,200 g preload)
      showed a low preference for barley on d 1 (.29) and 2 (.19) (P < .001). In Exp.
      2, lambs were assigned to four treatments (six lambs/treatment): 1) rolled barley
      + NaHCO3 (2%) + lasalocid (33 ppm); 2) rolled barley + NaHCO3 (2%); 3) rolled
      barley + lasalocid (33 ppm); or 4) rolled barley. Intake of barley by lambs
      offered NaHCO3 + lasalocid (Treatment 1) was greater (P = .07) than that by lambs
      offered NaHCO3 (Treatment 2), whereas intake by lambs offered lasalocid
      (Treatment 3) was similar (P > .05) to that by controls. We conclude that eating
      barley too frequently or in excess caused a decrease in lambs' preference for
      barley and that NaHCO3 and lasalocid attenuated the aversion.

PMID- 9655578
TI  - Evidence for three adult fast myosin heavy chain isoforms in type II skeletal
      muscle fibers in pigs.
AB  - Three main fiber types (one slow [type I] and two fast [type IIA and IIB] can be
      distinguished using conventional actomyosin ATPase (AM-ATPase) histochemistry
      after acidic pretreatment in mature pig skeletal muscle. We report the isolation,
      characterization, and identification of four adult 3'-untranslated regions
      corresponding to types I, IIA, IIB, and IIX myosin heavy chains (MyHC) from a
      cDNA library. Identification of different type II clones was based on sequence
      homology, in situ hybridizations (ISH), AM-ATPase histochemistry, and
      immunocytochemistry. Enzyme histochemistry, immunocytochemistry, and ISH were
      performed on serial transverse sections of longissimus and red portion of
      semitendinosus muscle. Results showed that all three fast MyHC transcripts were
      expressed in the longissimus, whereas only type IIA and IIX transcripts were
      present in deep red semitendinosus muscle. Type I and IIA fibers contained mostly
      type I and IIA transcripts, respectively, whereas type IIB fibers contained a
      heterogeneous population of transcripts. In longissimus muscle, 18, 31, and 51%
      of conventional IIB fibers were pure IIX, hybrid IIX/IIB, and pure IIB fibers,
      respectively. Conversely, conventional IIB fibers were actually IIX in deep red
      semitendinosus muscle. Expression of the three fast adult MyHC isoforms in
      longissimus was spatially regulated around the typical islets of type I fibers
      encountered in pig skeletal muscle. Thus, IIA fibers were contiguous to type I
      fibers, pure IIX fibers were in the direct vicinity of type I and IIA fibers, and
      hybrid IIX/IIB fibers were located mostly within primary fascicles between the
      islets of type I fibers; however, pure IIB fibers were located mainly at the
      periphery of the rosettes near the edges of primary fascicles. In light of the
      present study, conventional IIB fibers, as defined with AM-ATPase staining, are a
      heterogeneous population that should be split into pure IIX, hybrid IIX/ IIB, and
      pure IIB fibers for a more accurate fiber typing.

PMID- 9655579
TI  - Prediction of slaughter cow composition using live animal and carcass traits.
AB  - Slaughter cows (n = 120), representing four genotypes (British, continental, Bos
      indicus, and dairy) and three body condition classes (thin, moderate, and fat), n
      = 10 per subclass, were used to identify practical and accurate prediction
      equations for the yield of boneless manufacturing beef of specific fat
      percentages. Cows and their carcasses were weighed and evaluated for USDA yield
      and quality grade factors and for physical muscle and fat indicators. Carcass
      sides were fabricated; total fat percentage (TFP) was calculated as total fat
      (trimmed and chemical) divided by side weight, and tissue lean percentage (TLP)
      was calculated as boneless fat-free lean divided by soft tissue weight. Data were
      analyzed using maximum R2 multiple regression. The best live trait prediction
      model for TFP included live preliminary yield grade (LPYG), body condition score
      (LCOND), visual live muscle score (LMUSC), and live weight (LWT), R2 = .83. The
      best carcass trait TFP prediction model included adjusted preliminary yield grade
      (CPYGA); kidney, pelvic, and heart fat adjustment (CKPHADJ); marbling score
      (CMARB); and hot carcass weight (HCW), R2 = .92. The best live trait TLP
      prediction model included LPYG, LCOND, LMUSC, and LWT, R2 = .82. The best carcass
      trait TLP prediction model included CPYGA, CKPHADJ, CMARB, and lean maturity, R2
      = .91. These data indicate that TFP and TLP of slaughter cows can be accurately
      and practically predicted using live animal and carcass traits.

PMID- 9655580
TI  - Relative contributions of subcutaneous and intermuscular fat to yields and
      predictability of retail product, fat trim, and bone in beef carcasses.
AB  - Carcass data from one side of 610 steers born from 1988 to 1990 in Cycle IV of
      the Germ Plasm Evaluation research program were analyzed to develop means for
      carcass traits and retail product percentages at two fat trim levels (.76 and .00
      cm) by yield grade categories. Weights of subcutaneous (s.c.) fat and
      intermuscular (i.e.m.) fat were recorded separately at each trim level. Quadratic
      regression curves were plotted for percentages of roast and steak meat (R&S),
      retail product (RP), and fat trim components relative to incremental changes in
      USDA yield grade. Prediction equations were developed on a randomly chosen half
      of the 610 carcasses to predict weights and percentages of R&S, RP, and fat trim
      using carcass traits obtained at the time of USDA grading and then tested on the
      remaining half of the carcasses. In addition, prediction equations were developed
      using s.c. and i.e.m. fat plus carcass traits to evaluate the contribution of
      each to carcass fabrication yields. Percentage of RP, trimmed to either .76 cm or
      .00 cm of fat, decreased by an average of 3.5% for each full yield grade
      increase. Trimming to .00 cm of fat resulted in about 5.3% less RP compared to
      trimming to .76 cm. A prediction equation for percentage of RP trimmed to .00 cm
      using adjusted fat thickness, carcass weight, longissimus muscle area, and
      percentage of kidney knob had an R2 value of .54. The variations in percentage of
      R&S and percentage of RP at both trim levels were reduced by removing s.c. fat
      trimmed to .76 cm; however, considerable variation still existed. Subcutaneous
      fat expressed as a percentage of the sum of i.e.m. and s.c. fat increased as
      yield grade increased, but the percentage of i.e.m. fat was higher than the
      percentage of s.c. fat for all yield grades. On the basis of partial correlation
      coefficients, i.e.m. fat was approximately twice as important as s.c. fat in
      accounting for variations in fabrication yields.

PMID- 9655581
TI  - Retail yield and fabrication times for veal as influenced by purchasing options
      and merchandising styles.
AB  - Twenty-nine selected styles of subprimals or sections of veal were obtained from
      a commercial facility to assist in the development of a support program for
      retailers. They were fabricated into bone-in or boneless retail cuts and
      associated components by trained meat cutters. Each style selected (n = 6) was
      used to generate mean retail yields and labor requirements, which were calculated
      from wholesale and retail weights and processing times. Means and standard errors
      for veal ribs consisting of five different styles (n = 30) concluded that style
      #2, 7-rib 4 (10 cm) x 4 (10 cm), had the lowest percentage of total retail yield
      (P < .05) owing to the greatest percentage of bone. Furthermore, rib style #2
      required the longest total processing time (P < .05). Rib styles #3, 7-rib chop
      ready, and #5, 6-rib chop ready, yielded the greatest percentage of total retail
      yield and also had the shortest total processing time (P < .05). Within veal
      loins, style #2, 4 (10 cm) x 4 (10 cm) loin kidney fat in, had the greatest
      percentage fat (P < .05). Loin styles #2 and #3, 4 (10 cm) x 4 (10 cm) loin
      special trimmed, generated more lean and fat trimmings and bone, resulting in
      lower percentage of total retail yields than loin style #1, 0 (0 cm) x 1 (2.5 cm)
      loin special trimmed (P < .05). Results indicated that bone-in subprimals and
      sections required more processing time if fabricated into a boneless end point.
      In addition, as the number of different retail cuts increased, processing times
      also increased.

PMID- 9655582
TI  - Differences in natural steroid hormone patterns of beef from bulls and steers.
AB  - This investigation gives an overview of the concentrations of naturally occurring
      androgens, progestogens, corticosteroids, and their precursors and metabolites in
      meat from bulls and steers. A recently developed gas chromatography-mass
      spectrometry IGC-MS) method with improved sensitivity for steroid analysis was
      used. Eighty-two beef samples were analyzed using the GC-MS method. Beef from
      bulls contained higher concentrations of testosterone, which is an anabolic
      androgen, and its metabolite epitestosterone (P < .01) and the androgen precursor
      dehydroepiandrosterone (P < .05) than beef from steers. Beef from steers
      contained higher (P < .05) concentrations of the basic hormone precursor
      pregnenolone and cortisol, which is a catabolic corticosteroid, than beef from
      bulls. A classification of an unknown beef sample to one of the categories (bull
      or steer) was possible in most cases (>90%) using a masculinity index (MI) that
      was calculated using the concentrations of testosterone, epitestosterone, and
      pregnenolone. Because the hormonal status of beef cattle is related to meat
      quality characteristics, such as tenderness or fat and protein distribution, the
      MI may contribute to meat quality assessment and meat quality control.

PMID- 9655583
TI  - Selected lignosulfonate fractions affect growth performance, digestibility, and
      cecal and colonic properties in rats.
AB  - We determined the effects of lignosulfonate (LS) on nutrient digestibility and on
      hindgut fermentation characteristics using 80 adult male Sprague-Dawley rats fed
      a control diet or a diet containing 3% (dry matter basis) of seven selected LS
      fractions. Lignosulfonate fractions were divided into three categories: two
      fractionated whole calcium spent sulfite liquors (CaSSL) and one low-molecular
      weight permeate of CaSSL designated as WholeLS 1, 2, and 3, respectively; two
      extracted sodium LS (NaLS) fractions denoted as HighLS 1 and 2 (high percentage
      of NaLS); and two concentrated sugar solutions designated as LowLS 1 and 2 (low
      percentage of NaLS). All diets containing LS were less digestible (P < .001) than
      the control diet. Lignosulfonate treatment had a variable effect on short-chain
      fatty acid concentration except for LowLS 1, which tended to enhance butyrate
      concentration. Cecal organ weights were greater (P < .001) for LS treatments, but
      there was no difference in colonic organ weights. All cecal and colonic pH
      values, except the cecal pH for HighLS 2, were lower (P < .001) for LS treatment
      groups. Colonic Bifidobacterium increased (P < .005) with WholeLS 1 and 3 and
      HighLS 2 treatments. Cecal Lactobacillus levels were increased (P < .001) by
      WholeLS 1 and 2, LowLS 2, and HighLS 2. Results show that ingestion of selected
      LS fractions can modify digestive physiology and gastrointestinal tract
      characteristics of rats.

PMID- 9655584
TI  - L-ascorbyl-2-polyphosphate as a vitamin C source for segregated and
      conventionally weaned pigs.
AB  - We conducted two experiments to evaluate the efficacy of a stable source of
      vitamin C for improving performance and iron status in early-weaned pigs. A
      preparation of L-ascorbyl-2-polyphosphate (Rovimix Stay-C 25, Roche Vitamins,
      Ames, IA and Bramus, NJ), which supplies 25% ascorbic acid activity in a stable
      form, served as the vitamin C source and was incorporated at dietary vitamin C
      levels of 0, 75, or 150 ppm. In Exp. 1, 72 pigs (14 +/- 2 d of age and 4.98 kg
      BW) were blocked based on initial BW and penned in groups of three (eight pens
      per treatment) in an off-site nursery for 42 d. Phase 1 lasted from d 0 to 14,
      Phase 2 from d 14 to 28, and Phase 3 from d 28 to 42 after weaning. Daily gain
      and gain:feed ratio (G/F) increased during Phase 1 (quadratic, P < .1 and P <
      .05, respectively), Phase 3 (linear, P < .1 and P < .01, respectively), and for
      the overall 42-d experiment (linear, P < .05 and P < .1, respectively) in
      response to increasing dietary vitamin C. At 14 d after weaning, plasma vitamin C
      increased (linear, P < .05) with increasing dietary vitamin C, but plasma iron,
      hemoglobin, and hematocrit were not influenced by dietary vitamin C. In Exp. 2,
      120 pigs (20 +/- 3 d of age and 7.2 kg BW) were blocked based on initial BW and
      penned in groups of five (eight pens per treatment) in a conventional nursery
      system for 31 d. Phase 1 consisted of d 0 to 7, Phase 2 from d 7 to 17, and Phase
      3 from d 17 to 31 after weaning. During the period from d 0 to 17 after weaning,
      ADG and G/F were improved (linear, P < .1) with increasing dietary vitamin C. At
      d 17 after weaning, plasma vitamin C and serum iron increased (linear, P < .05),
      but unbound iron-binding capacity and total iron-binding capacity decreased
      (linear, P < .05 and P < .1, respectively) with increasing dietary vitamin C.
      These results suggest that dietary vitamin C is needed during the first 42 d
      after weaning when pigs are weaned as early as 12 d of age and reared in an off
      site nursery and during the first 17 d after weaning when pigs are weaned as
      early as 17 d of age and reared in a conventional nursery system. L-Ascorbyl-2
      polyphosphate at a supplemental level of 75 ppm was adequate to meet the dietary
      vitamin C requirement of early-weaned pigs. Vitamin C supplementation with a
      stable product will improve performance in young pigs during the high-stress
      postweaning period and may be particularly beneficial to pigs weaned at a very
      early age.

PMID- 9655585
TI  - Effect of ergotamine and ergonovine on plasma concentrations of thyroid hormones
      and cortisol in cattle.
AB  - Plasma samples from two experiments were processed to determine whether ergot
      alkaloids associated with endophyte-infected tall fescue altered peripheral
      thyroxine (T4), triiodothyronine (T3), or cortisol concentrations in cattle. In
      Exp. 1, seven Angus steers (294 kg) received i.v. bolus injections of saline
      (SAL), ergonovine maleate (7 mg; EM), or ergotamine tartrate (7 mg; ET) at weekly
      intervals, and they received all treatments during the study. Blood was sampled
      every 15 min for 5 h, and treatments were given after h 1. Mean ambient
      temperature was 34 degrees C. Treatment x time affected plasma concentrations of
      T3 (P < .05) and of cortisol (P < .001) but not that of T4 (P > .2). Plasma T3
      concentrations were not affected by SAL, whereas concentrations increased (P <
      .01) after either EM or ET treatment. Plasma cortisol concentrations were not
      altered by SAL or EM, but they were increased (P < .001) by ET treatment. In Exp.
      2, six Holstein cows (499 kg) nursing calves received a bolus i.v. injection of
      SAL, EM (9.5 mg), or ET (9.5 mg) per estrous cycle, and all treatments were given
      over three cycles. Blood was sampled every 20 min for 5 h; treatments were given
      after h 1. Mean ambient temperature was 26 degrees C. Treatment x time affected
      T3 (P = .08) and cortisol (P < .001) and tended to influence (P = .16) T4
      concentrations. Plasma T3, T4, and cortisol concentrations were not influenced by
      SAL treatment. Plasma T3 was higher (P < or = .01) after EM or ET treatment
      compared with pretreatment concentrations. Concentrations of T4 during the 4 h
      after EM and ET were increased (P < .001) compared with pretreatment. Plasma
      cortisol concentrations were not altered by EM but were increased (P < .001) by
      ET. Ergot alkaloids implicated as contributing agents to fescue toxicosis alter
      plasma concentrations of hormones important to metabolic and thermoregulatory
      functions in cattle.

PMID- 9655586
TI  - Functional activity of antibodies at the bovine beta2-adrenoceptor.
AB  - Antibodies that can activate beta2-adrenoceptors (beta2-AR) have the potential to
      mimic the anabolic effects of beta-agonist drugs, such as clenbuterol. In this
      study, antibodies were raised in rabbits against two peptide analogues of the
      human beta2-adrenoceptor (beta2-AR): One peptide corresponded to the complete
      second outer loop of the receptor (24 amino acids; H24T), and the second peptide
      was a truncated version of the first (13 amino acids; H13C). Following affinity
      purification, the antibodies were screened to detect interaction with beta2-AR in
      vitro. Membrane proteins from transformed Escherichia coli that express the beta2
      AR were separated using SDS PAGE and transferred to nitrocellulose sheets.
      Immunoblotting revealed a single protein band (39,000 Da) that was recognized by
      the affinity-purified anti-H24T antibodies. However, the anti-H13C antibodies did
      not recognize any protein bands in immunoblots. In ligand binding studies, anti
      H24T antibodies at a concentration of 50 nM, increased the affinity (KD) of the
      radiolabeled antagonist [125I]iodocyanopindolol for the bovine beta2-AR from 31.7
      pM to 25.3 pM (P < .05) without changing the receptor number. Anti-H13C
      antibodies had no effect on ligand binding. In competitive ligand binding
      experiments, there was no effect of antibodies on the affinity of bovine beta2-AR
      for the agonist (-)-isoproterenol. However, functional activity of anti-H24T
      antibodies was demonstrated in an organ bath study. The presence of antibodies
      caused a leftward shift in the concentration-response curve for (-)-isoproterenol
      induced relaxation of isolated bovine smooth muscle strips. Values for pD2 (-log
      EC50) were reduced in the presence of 10 nM antibody (8.62 +/- .11) compared to
      controls (8.30 +/- .08; P < .05). Anti-H13C antibodies had no effect on (-)
      isoproterenol-induced smooth muscle relaxation. These studies have demonstrated
      recognition, interaction, and functional activity of site-directed antibodies at
      the beta2-AR. Further studies will determine whether antibodies that potentiate
      activity at the beta2-AR may be evoked by the active immunization of cattle with
      the peptide H24T, and if so, whether this will cause the repartitioning of
      nutrients in a manner analogous to conventional beta2-agonists and thus provide
      an alternative to the use of xenobiotic compounds.

PMID- 9655587
TI  - Induced and synchronized estrus in cattle: dose titration of estradiol benzoate
      in peripubertal heifers and postpartum cows after treatment with an intravaginal
      progesterone-releasing insert and prostaglandin F2alpha.
AB  - Peripubertal beef heifers (n = 57) and postpartum multiparous cows (n = 52) were
      used to determine the optimal dose of estradiol benzoate (EB) to induce and
      synchronize estrus after treatment with intravaginal progesterone inserts (IVP4,
      EAZI-BREED CIDR). All females received an IVP4 for 7 d (d 0 = insertion day) with
      a 25-mg injection of PGF2alpha (Lutalyse) on d 6. At 24 to 30 h after IVP4
      removal, females were randomly assigned to be injected subcutaneously with EB at
      the following doses: heifers 0, .2, .38, or .75 mg and cows 0, .25, .5, or 1 mg.
      Furthermore, seven heifers and seven cows from each dose group were bled every 4
      h for 76 h starting at EB injection. Serum was collected and assayed for LH and
      estradiol-17beta (E2). Observations for signs of estrus were made twice daily for
      21 d after removal of IVP4, and females were artificially inseminated 8 to 20 h
      after detection of estrus. The percentage of females showing estrous behavior was
      increased by EB (P < .04); the greatest response was at .38 mg in heifers (86%)
      and 1 mg in cows (100%). Dose x time interaction affected (P < .01) E2
      concentrations in heifers and cows; the animals that received the higher doses of
      EB had greater E2 concentrations in a shorter time than those that received the
      smaller doses. The percentage of cows and heifers with an acute preovulatory LH
      release (peak LH) was affected by dose, with a linear (P < .01) and a quadratic
      (P < .01) response. Highest concentrations of LH during peak LH were affected by
      dose with a linear (P < .01) response in heifers and linear (P < .01) and
      quadratic (P < .08) responses in cows. Heifers receiving .38 mg and cows
      receiving .5 and 1 mg of EB had the highest peak LH. Time to LH peak had a linear
      (P < .03) response in heifers and had linear (P < .04) and quadratic (P < .05)
      responses in cows. Pregnancy rate was affected (P < .02) in heifers by whether or
      not they were anestrous before IVP4 treatment (those with estrous cycles = 52% vs
      those that were anestrous = 22%) and in cows by dose of EB (P < .01; 8, 23, 21,
      and 67% for 0, .25, .5, and 1 mg, respectively). In conclusion, in females
      treated with IVP4 and PGF2alpha to induce and synchronize estrus, an injection of
      EB increased concentrations of E2 and LH and increased number of animals showing
      estrus. Also, EB increased pregnancy rates in cows. Optimal responses were at .38
      mg EB for heifers and at 1 mg EB for cows.

PMID- 9655588
TI  - Expression of the angiogenic factors, basic fibroblast growth factor and vascular
      endothelial growth factor, in the ovary.
AB  - In adult tissues, vascular growth (angiogenesis) occurs normally during tissue
      repair, such as in the healing of wounds and fractures. Inappropriate vascular
      growth is associated with various pathological conditions. These conditions
      include tumor growth, retinopathies, hemangiomas, fibroses, and rheumatoid
      arthritis in the case of rampant vascular growth and nonhealing wounds and
      fractures in the case of inadequate vascular growth. The female reproductive
      organs exhibit dramatic, periodic growth and regression, accompanied by equally
      dramatic changes in their rates of blood flow. Thus, it is not surprising that
      they are some of the few adult tissues in which angiogenesis occurs as a normal
      process. Ovarian follicles and corpora lutea contain and produce angiogenic
      factors. These angiogenic factors bind heparin and seem to belong to the
      fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF)
      families of proteins. Based on our studies of the pattern of expression of FGF
      and its major receptors in bovine, ovine, and porcine corpora lutea, we have
      suggested that FGF may influence not only luteal cell proliferation but also cell
      death, thereby regulating cell turnover in the luteal vascular and nonvascular
      compartments. In addition, we recently have shown that luteal expression of VEGF
      is greatest during the early luteal phase, coincident with luteal
      vascularization. Moreover, VEGF is present exclusively in luteal connective
      tissue and perivascular (arteriolar smooth muscle and capillary pericyte) cells.
      In fact, the first thecal-derived cells to invade the granulosa-derived regions
      immediately after ovulation seem to be VEGF-containing pericytes. We have
      therefore hypothesized that ovarian pericytes play a key role in vascularization
      of developing follicles and corpora lutea. Further understanding of the specific
      physiological roles of these factors in follicular and luteal growth,
      development, and function will ultimately lead to improved methods of regulating
      fertility.

PMID- 9655589
TI  - Influence of season on dietary composition, intake, and digestion by beef steers
      grazing mixed-grass prairie in the northern Great Plains.
AB  - We used six beef steers (377 +/- 12.7 kg) to evaluate the effect of advancing
      season on dietary composition, forage intake, and digestion. Six 10-d sample
      collections were conducted from mid-June to mid-December 1995. Diet quality data
      demonstrated a linear (P < .01) decline in CP and in vitro OM digestibility
      (IVOMD), whereas NDF, ADF, acid detergent-insoluble CP (ADICP; percentage of CP),
      and undegradable intake protein (UIP; percentage of CP) increased linearly (P <
      .01) with advancing season. Fecal output and ruminal OM fill (percentage of BW)
      demonstrated linear and cubic responses (P < .10) across the grazing season.
      Intake of OM (percentage of BW) followed quadratic and cubic (P < .10) patterns
      across season. Rate (percentage per hour) of in situ NDF disappearance (ISNDFD)
      decreased and lag time increased linearly (P < .01) with advancing season.
      Likewise, quadratic (P < .07) and cubic (P < .06) responses were observed for
      rate and lag time of ISNDFD. The rapidly degraded CP fraction increased (P < .10)
      linearly, and the rate of in situ CP disappearance (ISCPD) followed a linear and
      quadratic decrease (P < .10) with advancing season. In summary, these data
      indicate decreases (P < .10) in dietary CP, IVOMD, ISNDFD, and ISCPD with
      advancing season. In addition, seasonal increases (P < .10) in forage NDF, ADF,
      ADICP, UIP (percentage of DM) and fecal output were observed and correspond to
      the grazing of increasingly mature forage. These data suggest that mixed-grass
      range forage consumed by cattle in western North Dakota during November and
      December is deficient in degradable intake protein (DIP). Investigation of
      protein supplementation (particularly DIP) during these times is warranted.

PMID- 9655590
TI  - Performance and digestion by steers grazing tall fescue and supplemented with
      energy and protein.
AB  - We studied the effects of different levels of protein and energy supplementation
      on BW gains and sites of nutrient digestion in steers grazing the primary growth
      of endophyte-infected tall fescue (Festuca arundinacea Schreb cv. Kentucky 31).
      Angus steers (n = 168; mean BW = 246.8 +/- 15.0 kg) grazed tall fescue without
      supplementation (C) or were supplemented with 1.4 kg/d of cracked corn (CC1), 1.4
      kg/d of corn gluten feed (CGF1), 2.8 kg/d of CC (CC2), 2.8 kg/d of CGF (CGF2), or
      .7 kg/d of cornstarch and .7 kg/d of corn gluten meal (CS-CGM) during an 85-d
      period in a randomized complete block design. Supplemented steers (S) had a
      higher (P = .03) ADG than the control steers (.64 vs .74 kg/d). There was an
      interaction (P = .02) between supplement type and level. Supplementation during
      the grazing period had no effect on subsequent feedlot ADG (average 1.3 kg/d). In
      a digestion study, Angus x Simmental steers (n = 4; 412 +/- 20.4 kg) fitted with
      cannulas in the esophagus, rumen, and duodenum grazed tall fescue (C), C + 3.1
      kg/d CGF, C + 3.1 kg/d of cracked corn (CC), or C + 1.4 kg/d CS-CGM over four
      experimental periods in a Latin square design. The ruminal ammonia nitrogen
      concentration tended to be higher (P < .09) in C than in CGF and in CC (21.9 vs
      19.2 mg/dL), but ruminal pH and total VFA concentration did not differ among
      treatments. Forage OM intakes were lower (P < .05) in steers supplemented with CC
      or CGF (an average of 7,570 g/d) than in C (9,658 g/d). Total OM intakes and
      digestibilities did not differ (P > .10) among treatments. Duodenal N flows and
      efficiencies of net ruminal microbial protein synthesis were not different (P >
      .10) among treatments. Supplementation of steers grazing primary growth of tall
      fescue improved animal gain but did not have a great effect on ruminal
      fermentation, OM digestion, or net ruminal microbial protein synthesis.

PMID- 9655591
TI  - Calculation of the buffering capacity of bicarbonate in the rumen and in vitro.
AB  - We describe a model to calculate the buffering capacity of bicarbonate in the
      rumen. The addition of NaHCO3 results in the release of CO2 from solution and
      eventually from the rumen via eructation. This process directly neutralizes
      ruminal acidity. The degree to which the process continues depends on the partial
      pressure of CO2 in the gas phase, the pH, and a constant (7.74), according to the
      Henderson-Hasselbalch equation: pH = 7.74 + log([HCO3-]/pressure of CO2 in
      atmospheres). The addition of NaHCO3 to buffer solutions and ruminal fluid under
      high pressure of CO2 increased pH as predicted. The buffering capacity of ruminal
      fluid under CO2 was greater at low pH than was previously determined by titration
      in air. In contrast, in vitro systems in which CO2 is not permitted to escape may
      result in reduced buffering capacity. In vitro systems in which excess CO2 may
      escape (under N2 gas pressure) may result in uncontrolled pH elevation. Dilution
      of ruminal fluid under constant pressure of CO2 decreased ruminal pH as predicted
      by the model. The pH under different pressures at equilibrium and the buffering
      capacity are easily calculated for in vitro and in vivo systems.

PMID- 9655592
TI  - The effect of teaching approaches on achievement and satisfaction of field
      dependent and field-independent learners in animal science.
AB  - A senior-level university swine management class of 42 students consisted of
      three laboratory sections (containing 22, 12, and 8 students). A counterbalanced
      design was used to evaluate three teaching approaches (field-dependent, field
      independent, and combination); each weekly laboratory section received each
      teaching approach for 3 wk. All students were evaluated and categorized as field
      dependent or field-independent learners before the study. All students were
      evaluated for achievement and satisfaction at the end of each laboratory period.
      Teaching approach x learning style x laboratory section was not significant for
      achievement or satisfaction. Teaching approach x laboratory section was
      significant for achievement (P = .01) and satisfaction (P = .01). Teaching
      approach x learning style was not significant for achievement (P = . 15) or
      satisfaction (P = .15). Field-independent learners scored 6% higher on
      achievement tests when taught with a field-dependent approach rather than a field
      independent approach. Field-dependent learners scored 21.9% higher when taught
      with a combination approach rather than a field-dependent approach and 13.8%
      higher than when taught with a field-independent approach. Overall student
      satisfaction was positive (3.50 on a 5-point scale). Field-independent learners
      were most satisfied with a combination approach; however, field-dependent
      learners preferred a field-dependent approach. Teaching approach was significant
      (P = .03) for achievement with the combination approach and resulted in higher
      scores (8.7 to 9.7%). Teaching approach was not significant for satisfaction (P =
      .61). Overall, a combination of teaching methods, tailored to both field
      dependent and field-independent students, was most effective. Matching
      instruction to student learning style is not necessary. The study represents an
      example of using animal science students and faculty in research to improve
      animal science instruction and heighten awareness of teaching methods.

PMID- 9655593
TI  - Rapid communication: A PCR-RFLP marker at the porcine complement factor B gene
      locus shows between-population frequency variation.

PMID- 9655594
TI  - Rapid communication: a PCR amplified product length polymorphism (APLP) marker at
      the porcine glucosephosphate isomerase locus shows between-population frequency
      variation.

PMID- 9655595
TI  - Rapid communication: Nucleotide sequence of the coding region for the porcine
      beta1-adrenergic receptor gene.

PMID- 9655596
TI  - Which afferents induce and transmit dorsal root reflex in rats?
AB  - The dorsal root reflex (DRR) in single fibers, recorded in the severed L5 dorsal
      root central stump, initiated spontaneously or by electric stimulation (St) of
      sciatic nerve, was studied in anesthetized rats. The excitation of group II
      afferents were the major inputs to induce DRRs which were transmitted mainly in
      fibers with conduction velocity below 20 m/s, and its central delay was 3-5 ms.
      The firing frequency of both spontaneous and evoked DRRs were increased two to
      four times after spinalization (T13). These results suggested that the DRR may
      play an important role in the modulation of sensory afferent inputs regulated by
      supraspinal structures.

PMID- 9655597
TI  - Regional changes of NADPH-diaphorase and neuropeptide Y neurons in the cerebral
      cortex of aged Fischer 344 rats.
AB  - This study examined the effects of aging on neuropeptide Y (NPY) and NADPH
      diaphorase (NADPH-d)-positive neurons of the cerebral cortex in young (3 months)
      and aged (24 months) Fischer 344 rats by immunohistochemical and histochemical
      methods. In the aged group, the number of NPY-immunoreactive (IR)/NADPH-d
      positive neurons was not significantly changed in all regions of the cerebral
      cortex compared to the control group. However, the number of NPY-IR/NADPH-d
      negative neurons was significantly decreased in frontal association, primary
      motor, secondary somatosensory, insular, ectorhinal, perirhinal and auditory
      cortex in the aged group. In the aged rats, about 5-10% of NPY-IR/NADPH-d
      positive neurons were dystrophic and scattered within the cerebral cortex. These
      results suggested that NPY-IR neurons that do not contain NADPH-d are affected by
      aging and that aging influences NPY-IR/NADPH-d-negative neurons in a region
      specific pattern within the cerebral cortex of rats.

PMID- 9655598
TI  - Coexpression of phospholipase A2 isoforms in rat striatal astrocytes.
AB  - The expression and activity of phospholipase A2 (PLA2) isoforms were investigated
      in primary cultures of striatal astrocytes. The calcium ionophore A23187 together
      with the protein kinase C activator phorbol ester was the most potent stimulus in
      eliciting [3H]arachidonic acid release in the extracellular medium. Reverse
      transcription coupled to polymerase chain reaction (RT-PCR) showed the presence
      of the 85 kDa cytosolic PLA2 mRNA and the 14 kDa secretory PLA2 mRNA in untreated
      astrocytes. Immunoblot experiments with isoform-specific antibodies showed the
      presence of the cytosolic PLA2 in untreated astrocytes, while the secretory PLA2
      was detected only in lipopolysaccharide-treated astrocytes. These data suggest
      that the two PLA2 isoforms expressed in striatal astrocytes might play different
      roles in cellular processes mediated by astrocytes.

PMID- 9655599
TI  - Ca2+-H+ antiport activity in synaptic vesicles isolated from sheep brain cortex.
AB  - Synaptic vesicles isolated from sheep brain cortex exhibit an ATP-dependent Ca2+
      accumulation that is inhibited by the protonophore uncoupler carbonyl cyanide m
      chorophenylhydrazone (CCCP) and completely released by the Ca2+ ionophore
      ionomycin. This transport activity was sensitive to the V-type ATPase inhibitor,
      bafilomycin, but not to the P-type ATPase inhibitor, vanadate. We also observed
      that the proton gradient, established across the synaptic vesicle membranes in
      the presence of ATP, is partially dissipated by the addition of Ca2+ (100-860
      microM) in correlation to an increase of ATP hydrolysis by the H+-pumping ATPase.
      In contrast, the activity of the H+-ATPase, measured under uncoupling conditions
      (presence of CCCP), appears to be unaltered by the calcium ion. The Ca2+-induced
      H+ release visualized by fluorescence quenching of acridine orange correlates
      well with the Ca2+ uptake determined isotopically. These results indicate that
      synaptic vesicles accumulate Ca2+, via a low affinity Ca2+-H+ antiport system
      energized by the protonmotive force originated from the H+-pumping ATPase
      activity.

PMID- 9655600
TI  - Morphological heterogeneity of cultured spinal and cerebral rat oligodendrocytes.
AB  - Oligodendrocytes in different central nervous system regions have dissimilar
      morphologies. In order to find out if immature oligodendrocytes develop different
      phenotypes spontaneously, neonatal spinal and cerebral rat oligodendrocytes were
      cultured in vitro in the absence of neurons. The results show that spinal
      oligodendrocytes tend to develop a bipolar structure with few processes, while
      cerebral cells tend to become multipolar with many processes. A similar spinal
      cerebral difference was seen in oligodendrocyte-enriched cultures. Hence, spinal
      and cerebral oligodendrocytes develop partly different morphologies in vitro.

PMID- 9655601
TI  - Imidazoline receptor proteins in brains of patients with Alzheimer's disease.
AB  - Imidazoline receptors (29/30- and 45-kDa proteins) were quantitated in postmortem
      brains of patients with Alzheimer's disease (AD) by using immunoblotting
      techniques and a specific antiserum. Increased levels of the 29/30-kDa protein
      (30%), 45-kDa protein (36%) and glial fibrillary acidic protein (88%) were found
      in the frontal cortex of AD patients. These findings are in line with the
      reported higher density of imidazoline receptors labelled by [3H]idazoxan in AD
      brains, suggesting that these imidazoline receptor proteins are related to the I2
      imidazoline receptor located in mitochondria of glial (astrocyte) cells.

PMID- 9655602
TI  - Progressive accumbens degeneration after neonatal striatal 6-hydroxydopamine in
      rats.
AB  - Parkinson's disease is associated with progressive loss of nigrostriatal dopamine
      (DA). Models of the disorder, produced with neurotoxins (N-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine or 6-hydroxydopamine) that selectively lesion DA
      neurons, are characterized by acute removal and gradual recovery of DA. We report
      slowly progressive loss of DA in ipsilateral nucleus accumbens following profound
      (>90%) acute unilateral depletion of DA in the caudate-putamen of neonatal rats,
      from 50% at age 27 days to 94% by 100 days. Metabolic turnover of DA markedly
      increased in ipsilateral accumbens, and may yield tissue-damaging neurotoxic by
      products. This paradigm may help in elucidating mechanisms responsible for
      gradual degeneration of DA neurons and for screening potential neuroprotective
      agents.

PMID- 9655603
TI  - Role of calcium in the activation of erp72 and heme oxygenase-1 expression on
      depletion of endoplasmic reticulum calcium stores in rat neuronal cell culture.
AB  - Endoplasmic reticulum (ER) calcium pool depletion was induced by 30 min exposure
      of primary neuronal cells to thapsigargin (Tg), an irreversible inhibitor of ER
      Ca2+-ATPase. Twelve hours later, erp72 and heme oxygenase-1 (HO-1) mRNA levels
      were quantified by PCR. Protein synthesis was also measured. Transient Tg
      exposure of neurons induced a marked rise in mRNA levels (7-fold and a 21-fold
      increase in erp72 and HO-1 mRNA levels; P < 0.001). Loading of neurons with the
      calcium chelator 1,2-bis(o-Aminophenoxy)ethane-N,N,N',N'
      tetra(acetoxymethyl)ester (BAPTA-AM) prior to thapsigargin treatment had only a
      minor effect on the Tg-induced rise in gene expression. This small inhibitory
      effect may result from the severe suppression of protein synthesis caused by
      BAPTA-AM. The results suggest that the increase in stress gene expression induced
      by exposure of neurons to Tg is triggered by a decrease in ER calcium activity
      and not by the corresponding increase in cytoplasmic calcium activity.

PMID- 9655604
TI  - Nicotinic agonists competitively antagonize serotonin at mouse 5-HT3 receptors
      expressed in Xenopus oocytes.
AB  - The 5-HT3 receptor (5-HT3R) is part of a superfamily of ligand-gated ion channels
      which includes nicotinic acetylcholine receptors (nAChR). cRNA derived from the
      long isoform cloned mouse 5-HT3R was used to drive expression of 5-HT3Rs in
      Xenopus oocytes. 5-HT-induced currents were monitored using two-electrode voltage
      clamp. Eight nicotinic agonists, including ACh and nicotine, but not alpha
      anatoxin, were found to antagonize 5-HT-induced currents. With the exception of 3
      (2,4)-dimethoxybenzylidene-anabaseine (DMXB-anabaseine; GTS-21) this antagonism
      appeared to be competitive since it could be overcome by increasing
      concentrations of 5-HT. Potency of 5-HT3 antagonism was comparable to reported
      values for nAChR alpha7 activation. These results confirm the notion of families
      of receptors and further indicate that strong similarities can exist in some
      critical binding domains.

PMID- 9655605
TI  - Preparation of cell suspensions for co-transplantation: methodological
      considerations.
AB  - The purpose of the current study was to determine the optimal strategy for
      preparing cell suspensions for co-transplantation. In the first experiment, the
      number of Sertoli cell (SC) aggregates and the number of tyrosine hydroxylase
      positive neurons were compared over time when cell suspensions of Sertoli or
      ventral mesencephalic cells were kept as a co-suspension mixed at 0 h. Cells from
      each suspension were dispensed onto glass slides in a manner similar to
      transplantation. When dispensed in this manner, the number of SC aggregates and
      TH-positive neurons decreased over 4 h. In experiment 2, the cell suspensions
      were mixed just prior to injection at each of four timepoints, the number of
      aggregates and TH neurons was consistent over time. Clearly this latter strategy
      resulted consistent recovery of both cell types for transplants up to 3 h after
      suspension preparation.

PMID- 9655606
TI  - Dynorphin uses a non-opioid mechanism to potentiate N-methyl-D-aspartate currents
      in single rat periaqueductal gray neurons.
AB  - The interaction of the endogenous K-opioid, dynorphin, with N-methyl-D-aspartate
      (NMDA) receptors was studied in single periaqueductal gray (PAG) cells using the
      whole cell patch recording technique. We have found that dynorphin A (1-17)
      rapidly and reversibly potentiates NMDA-activated currents in a subpopulation of
      PAG cells. The potentiation cannot be blocked by the non-specific opioid
      antagonist, naloxone, nor can it be reversed by the specific kappa-opioid
      antagonist, nor-BNI. In addition, the non-opioid fragment of dynorphin, dynorphin
      A (2-17), is effective in potentiating NMDA currents, while the specific kappa
      opioid, U50,488, cannot mimic the action of dynorphin A (1-17). The non-opioid
      dynorphin action and the rapid onset and recovery of the potentiation are
      consistent with the idea that dynorphin interacts directly with NMDA receptors in
      PAG cells.

PMID- 9655607
TI  - The effect of excitatory aminoacids on GABA release from mediobasal hypothalamus
      of female rats.
AB  - The purpose of the present study was to examine the in vitro effect of L
      glutamate and its agonists on basal and potassium-evoked GABA release from
      incubated mediobasal hypothalamus (MBH) of intact, ovariectomized (OVX) and OVX
      estrogenized female rats. L-glutamate (100 microM) decreased evoked GABA release
      from MBH of intact female rats in diestrus. NMDA and quisqualate (10 and 100
      microM) modified neither basal nor evoked hypothalamic GABA release of intact
      rats. However, kainate (10 and 100 microM) decreased hypothalamic basal and
      evoked GABA release of intact rats. Kainate induced no changes in basal or in
      evoked GABA release from hypothalami of OVX rats, but decreased GABA release in
      chronically estrogenized rats. DNQX (6,7-dinitroquinoxaline-2,3-dione), a non
      NMDA receptor antagonist, failed to affect GABA release but blocked the
      inhibitory effect of kainate. The kainate effect was not Mg2+-sensitive and was
      not inhibited by D-AP5 (D(-)-2-amino-5-phosphonopentanoic acid), an NMDA-specific
      receptor antagonist. Kainate induced no changes in nitric oxide synthase activity
      in MBH of either intact or estrogenized rats. These data indicate that kainate
      decreases GABA release from MBH of female rats through a non-NMDA receptor
      subtype, and provide evidence to support the view that kainate-mediated decrease
      of the hypothalamic GABAergic tone is affected by estrogens.

PMID- 9655608
TI  - Malic enzyme isoforms in astrocytes: comparative study on activities in rat brain
      tissue and astroglia-rich primary cultures.
AB  - Anion exchange chromatography on diethylaminoethyl cellulose was optimized to
      separate the cytosolic and mitochondrial isoforms of malic enzyme from rat brain.
      Extracts of adult rat brain and of astroglia-rich primary cultures derived from
      the brains of newborn rats were analyzed for their content of the two isozymes.
      In the case of brain tissue 45% of malic enzyme activity was due to the cytosolic
      isoform. In contrast, in extracts from astroglia-rich primary cultures more than
      95% of the total activity was associated with the cytosolic isozyme. From these
      data it is concluded that the cytosolic rather than the mitochondrial isoform of
      malic enzyme has prominent functions in astroglial metabolism.

PMID- 9655609
TI  - Removal of GABAergic inhibition in the mediodorsal nucleus of the rat thalamus
      leads to increases in heart rate and blood pressure.
AB  - The mediodorsal nucleus of the thalamus (MD) has connections with central
      autonomic centers involved in cardiovascular control and undergoes severe
      degeneration in fatal familial insomnia, a human disease characterized by
      progressive dysautonomia. Microinjections of the GABAA antagonist bicuculline
      methiodide (BMI) into the medial and central portion of the MD lead to
      significant, dose-dependent increases in both heart rate and blood pressure.
      Similar injections into surrounding regions elicited little to no change. The
      data suggest that the medial and central portion of the MD plays a role in
      central cardiovascular regulation. Neurons of the MD may be under tonic GABAergic
      inhibition, and disruption of circuits at this level may underlie dysautonomia in
      many neurological diseases.

PMID- 9655610
TI  - Melatonin restores and enhances the human type B tonsillar lymphocyte subset in
      recurrent acute tonsillitis.
AB  - Tonsils have a privileged situation in the immune system in that they are in
      touch with the environment. Melatonin is a hormone that is influenced by the
      circadian environmental variations of dark-light and is a modulator of the immune
      system. We have studied a group of thirty five children with recurrent acute
      tonsillitis that were submitted for tonsillectomy. Tonsillar lymphocyte subsets
      were determined before and after culture through flow cytometry in a tonsillar
      mononuclear suspension. After the culture, the lymphocyte subsets of type B
      suffered a decrease that was restored in the presence of melatonin or
      phytohemaglutinin, and even increased above the values of the control when the
      culture was accomplished in the presence of both substances. This process was
      specific for B cells, no occurrence for T lymphocytes or natural killer cells.
      Melatonin is found in the crossroads of the interaction of the microorganisms,
      pollens or inert substances with the tonsillar lymphocytes in the production of
      the immune defences. Further study is required on tonsillar pathology to explain
      its physiopathology and its possible therapeutic role.

PMID- 9655611
TI  - Neurons as well as astrocytes express proteoglycan-type protein tyrosine
      phosphatase zeta/RPTPbeta: analysis of mice in which the PTPzeta/RPTPbeta gene
      was replaced with the LacZ gene.
AB  - PTPzeta/RPTPbeta is a receptor-like protein tyrosine phosphatase expressed as a
      chondroitin sulfate proteoglycan. We generated mice in which the PTPzeta gene was
      replaced by the LacZ gene by gene targeting. Analysis of heterozygous PTPzeta
      targeted mice allowed us to identify PTPzeta-producing cells during development
      by examining expression of the LacZ gene. LacZ expression was detected only in
      the central nervous system throughout development from embryonic day 8.5. In the
      postnatal period, subsets of neurons and astrocytes in the brain, including
      pyramidal cells and astrocytes in the hippocampus, expressed LacZ. Primary
      cultures of cells from the cerebral cortex of embryonic day 16 mice also
      indicated that both neurons and astrocytes were positive for LacZ. These results
      indicated that neurons and astrocytes express PTPzeta.

PMID- 9655612
TI  - Modulation of glutamate sensitivities by inhibitors of a protein kinase and a
      protein phosphatase in cultured rat Purkinje cells.
AB  - We examined the effects of inhibitors of calcium-calmodulin-dependent protein
      kinase II (CaM kinase II) and protein phosphatases on the glutamate (Glu)
      responses in cultured rat cerebellar Purkinje cells. CaM kinase II inhibitors
      significantly potentiated Glu responses, and activation of metabotropic Glu
      receptors facilitated this potentiation. In contrast, a phosphatase inhibitor
      calyculin A significantly reduced Glu responses. It was suggested that the Glu
      responsiveness of Purkinje cells may be regulated by the dynamic balance of
      phosphorylation and dephosphorylation of receptors or other relevant factors
      under basal conditions.

PMID- 9655613
TI  - Talipexole protects dopaminergic neurons from methamphetamine toxicity in
      C57BL/6N mouse.
AB  - The effect of protection of dopaminergic neurons by talipexole, a dopamine (DA)
      agonist, is investigated on a methamphetamine (MA)-induced parkinsonism model of
      mice (C57BL/6N). The reduction of tyrosine hydroxylase activity in the striatum
      72 h after MA (5 mg/kg every 2 h, four times) treatment was attenuated by the
      administration of talipexole (0.25 mg/kg or 1.0 mg/kg) prior to the
      administration of MA. In an in vitro experiment, talipexole inhibited the
      adduction reaction of hydroxyl radicals to salicylate. Taken together, these data
      suggest that the protective effect of talipexole on DA neurons is, in part,
      caused by the hydroxyl radical-scavenging action of the drug.

PMID- 9655614
TI  - Characterization of a plasma membrane zinc transporter in rat brain.
AB  - Many studies now show that zinc plays a critical and unique role in central
      nervous system development and function. The cellular mechanisms of zinc efflux
      and influx are largely unknown and few models exist that describe cellular zinc
      transport in the brain. This report provides convincing evidence of a zinc
      transporter in plasma membrane vesicles isolated from rat brain. Zinc uptake was
      saturable (Km = 15 microM; Vmax = 10 nmol/mg per 30 s), was seen in the absence
      of ATP, and was unaffected by gradients for other ions such as Na+ or K+.
      Increasing the ionic strength of the extravesicular media with Na+, K+, or
      choline+ reduced zinc uptake approximately 50%. Whereas, increasing
      extravesicular H+ concentration (pH = 5) resulted in near complete inhibition of
      zinc uptake. Intravesicular zinc was rapidly released upon lowering
      extravesicular concentrations of zinc with the heavy metal chelator O
      phenanthroline (1 mM). The results are consistent with a freely-reversible
      transport of zinc across the plasma membrane of neurons.

PMID- 9655615
TI  - Spontaneous regeneration of the pyramidal tract after transection in young rats.
AB  - Spontaneous regeneration of the pyramidal tract after transection of the
      medullary pyramid was examined in young rats by the anterograde tracing method
      with wheat germ agglutinin-conjugated horseradish peroxidase. Care was taken to
      cut the tract as sharply as possible to minimize traumatic injuries. A very sharp
      cut produced edema-free lesions without subsequent formation of either cysts or
      scars, whereas a relatively blunt cut produced edema and later scars and/or cysts
      in the lesion. Regenerated projections in the latter cases were sparse, short,
      dispersed and largely aberrant as described in previous reports. By contrast,
      regenerated projections in the former cases were very much similar to normal in
      various respects: the amount, extension, path, formation of a compact bundle and
      termination. There was, however, a decisive difference from normal, that is, the
      additional aberrant projections.

PMID- 9655616
TI  - Low and high frequency electroacupuncture at Hoku elicits a distinct mechanism to
      activate sympathetic nervous system in anesthetized rats.
AB  - To address the effect of electroacupuncture (Ea) on autonomic nerve activity, the
      responses of rhythmic micturition contraction (RMC), urine excretion (UE), blood
      pressure (BP), renal sympathetic nerve activity (RNA) and pelvic parasympathetic
      nerve activity (PNA) to Ea were investigated in urethane-anesthetized rats. The
      acupoint Hoku (Li-4) was tested with two different stimulation frequencies (2 Hz
      and 20 Hz). Elongation of the RMC cycle and an increase in UE associated with the
      elevation of BP and RNA was elicited during Ea at Hoku. However, the pressor
      response induced by low frequency Ea (LFEa) was different from that by high
      frequency Ea (HFEa), i.e. a tonic effect was elicited by LFEa, while a phasic one
      was induced by HFEa. These results imply that: (1) Ea at Hoku may selectively
      activate the sympathetic, but not the parasympathetic nervous system, (2) Ea at
      Hoku with a different stimulation frequency may elicit a distinct mechanism to
      activate the sympathetic nervous system and (3) Ea at Hoku may ameliorate the
      hyperactive bladder in clinical therapy.

PMID- 9655617
TI  - Colocalization of Bcl-2 and 4-hydroxynonenal modified proteins in microglial
      cells and neurons of rat brain following transient focal ischemia.
AB  - Bcl-2 has a role in suppressing the production of reactive oxygen species and
      lipid peroxidation. To explore the in situ localization of 4-hydroxy-2-nonenal
      (HNE)-modified proteins and the Bcl-2 oncoprotein, we used double
      immunofluorescence labeling and confocal imaging in the rat brain after 3 h of
      middle cerebral artery (MCA) occlusion followed by reperfusion. Immunoreactivity
      for HNE or Bcl-2 was not detected at 1 h, but appeared in some intact neurons in
      the boundary between the infarcted and non-infarcted zones at 12 h. At 48 h, HNE
      positive microglia were colocalized with Bcl-2 in the infarcted area and the
      boundary zone. Bcl-2 may play an important role in the antioxidant system
      promoting survival of the neurons and activated microglia following reperfusion
      injury.

PMID- 9655618
TI  - Recoverin and hippocalcin distribution in the lamprey (Lampreta fluviatilis)
      retina.
AB  - Recoverin is a calcium-sensing protein which is involved in the transduction of
      light in vertebrate photoreceptors. It is also detected in other retina cell
      types in which its function is not yet elucidated, and is an autoantigen in a
      cancer-associated degenerative disease of the retina. Recently, hippocalcin, an
      homologous protein of recoverin, belonging to the same family of fatty acylated
      EF-hand calcium binding proteins was described in mammals. The
      immunohistochemical studies presented in this paper demonstrate, that, in the
      retina of the lamprey, an Agnathan considered the living ancestor of actual jawed
      vertebrates, recoverin was present in all photoreceptors and, to a lesser extent
      in subpopulations of amacrine and ganglion cells whereas hippocalcin was detected
      in numerous amacrine and ganglion cells and in the inner segments of long
      photoreceptors. The existence of these calcium-binding proteins shows that they
      have a high degree of conservation during evolution. Their presence in the same
      cells that in jawed vertebrates (photoreceptors and ganglion cells for recoverin;
      amacrine and ganglion cells for hippocalcin) suggests that some retinal functions
      are well conserved but because they were also found in different cell types than
      in other species (amacrine for recoverin; photoreceptors for hippocalcin), they
      may have functions more specific to the lamprey retina.

PMID- 9655619
TI  - Autoradiographic localisation of muscarinic cholinergic receptor subtypes in
      human placenta.
AB  - The localisation of M1-M4 muscarinic cholinergic receptor subtypes was
      investigated in sections of normal human term placenta by light microscope
      autoradiography. Muscarinic cholinergic receptor subtypes were found almost
      exclusively in syncytiotrophoblast. Neither other cellular components of
      placenta, nor blood vessels were labelled. Quantitative analysis of the density
      of silver grains developed in sections incubated with the different protocols for
      labelling M1-M4 receptor subtypes, revealed that syncytiotrophoblast expresses
      all subtypes of muscarinic cholinergic receptor investigated. A higher density of
      binding sites was found in the apical than in the basal portion of
      syncytiotrophoblast. The demonstration of muscarinic cholinergic receptors in
      syncytiotrophoblast suggests that a cholinergic system may have a role in
      regulating transport of compounds from maternal to foetal interface.

PMID- 9655620
TI  - Impaired short- and long-term memory in Ts65Dn mice, a model for Down syndrome.
AB  - Ts65Dn (TS), control littermates (CO) and Swiss (SW) male mice were tested in the
      elevated plus-maze and in the Morris water maze (MWM) for memory evaluation. In
      the plus-maze, each mouse was placed at the end of an open arm and initial
      freezing and the time to enter into an enclosed arm (transfer latency) were
      measured. SW mice decreased both measures over repeated trials, whereas no
      decrease of freezing was observed in CO mice, thus suggesting increased
      emotionality in this group. Compared to CO mice, TS mice showed less initial
      freezing, shorter transfer latencies, and spent less time in enclosed arms,
      suggesting a reduced ability to habituate or to inhibit behaviour. Animals were
      also submitted to a learning-set paradigm consisting of reaching a new platform
      position each day in the MWM. Two training phases (separated by a resting period
      of 6 weeks), each including eight acquisition and four cued sessions, were
      performed (each session consisting of four pairs of trials). CO and SW mice
      already reached an asymptotic performance by the second day of the first phase
      whereas TS mice did not achieve that level until the second training phase. The
      progression over trials indicated that CO and SW animals learned the new platform
      position between trials 1 and 2 of each session, whereas TS animals failed to do
      it and had more difficulties to find the platform when it was placed in the
      centre of the pool as compared to the other positions (SW, NE, E). The results
      suggest that TS mice show working memory impairments in addition to long-term
      memory deficits, although extensive training appeared to facilitate TS mice to
      achieve a level of performance similar to their control littermates. This
      represents another aspect of the cognitive deficits shown by TS mice: a mouse
      model of the human Down syndrome.

PMID- 9655621
TI  - Inwardly rectifying K+ currents in intermediate cells in the cochlea of gerbils:
      a possible contribution to the endocochlear potential.
AB  - The stria vascularis in the cochlea generates the endocochlear potential (EP) and
      secretes K+-rich endolymph; both are indispensable for normal sound transduction
      by hair cells. K+ conductance in the intermediate cell, one of the several types
      of cells constituting the stria vascularis, was investigated by the whole-cell
      patch-clamp technique. Inwardly-rectifying K+ (Kir) currents were the major
      currents observed. The currents were inhibited dose-dependently by Ba2+, quinine,
      verapamil and Cs+, but not by tetraethylammonium (20 mM), 4-aminopyridine (5 mM)
      or Cd2+ (1 mM). The similarity between the effect of inhibitors on Kir currents
      and on the EP (Takeuchi et al., Hearing Res., 101 (1996) 181-185) suggests a
      direct contribution of the Kir conductance to the generation of the EP.

PMID- 9655622
TI  - Cholinergic, but not the rod pathway-related glycinergic (All), amacrine cells
      contain calretinin in the rat retina.
AB  - Double-label immunocytochemistry was carried out on cryostat sections of rat
      retina to test for the presence of calretinin in cholinergic starburst and the
      rod pathway-related glycinergic (All) amacrine cells. All cholinergic cells
      contained calretinin, but calretinin-immunoreactive cells were much more numerous
      in both the inner nuclear and ganglion cell layers than the cholinergic cells.
      Glycinergic All amacrine cells have been found to contain calretinin in cat,
      monkey and rabbit retinas. Since All amacrine cells in rat can be selectively
      labeled with antibodies against parvalbumin, in a second experiment we attempted
      to colocalize these proteins. We found that calretinin- and parvalbumin
      immunoreactive neurons belonged to distinct amacrine cell populations permitting
      the conclusion that, in the rat retina, All amacrine cells do not contain
      calretinin. The results indicate that even those amacrine cells of the mammalian
      retina that are highly conserved with respect to morphology and transmitter
      content, may differ with respect to other neurochemical characteristics, such as
      their calcium-binding proteins.

PMID- 9655623
TI  - Effect of spinal cord stimulation on tactile hypersensitivity in mononeuropathic
      rats is potentiated by simultaneous GABA(B) and adenosine receptor activation.
AB  - In rats with abnormally low withdrawal thresholds ('allodynia') in one hindpaw
      induced by a photochemical sciatic lesion, an intrathecal catheter was inserted
      to the lumber enlargement and an epidural electrode was implanted at T11. I.t.
      administration of GABA(B) or adenosine A1 receptor agonists (baclofen, R(-)-N6-(2
      phenylisopropyl)adenosine (R-PIA)) suppressed allodynia in a dose-dependent
      fashion. When the two agonists were given together, each in an ineffective dose,
      there was a normalization of the thresholds. Rats, in which spinal cord
      stimulation (SCS) could not suppress the allodynia (non-responders), were
      transformed into SCS-responders by injection of baclofen and R-PIA in low,
      ineffective doses, combined with SCS. In SCS responding rats, combination of a
      selective GABA(B) and an adenosine A1 receptor antagonist (CGP 55845, CPT) in
      low, ineffective doses abolished the SCS-induced threshold normalization. These
      results indicate that GABAergic and adenosine-dependent mechanisms are involved
      in the SCS effect and further suggest a strategy for enhancing the therapeutic
      efficacy of SCS.

PMID- 9655624
TI  - Does the cerebellum contribute to cognitive aspects of speech production? A
      functional magnetic resonance imaging (fMRI) study in humans.
AB  - Several positron emission tomography (PET) studies suggest a contribution of the
      lateral aspects of the right cerebellar hemisphere to higher-level (cognitive)
      aspects of speech production such as controlled verbal response selection. As an
      alternative, however, 'inner speech', giving rise to subliminal activity of
      orofacial and laryngeal muscles, might account for the observed activation
      effects. Eighteen subjects underwent functional magnetic resonance imaging (fMRI)
      during continuous silent recitation of the names of the months of the year
      ('automatic speech'). The right cerebellar hemisphere showed a significantly
      increased hemodynamic response concomitant with, among others, an asymmetric
      activation pattern towards the left side at the level of the motor strip. Since
      highly overlearned word strings, presumably, pose few demands on controlled
      response selection and since the projections of the right cerebellar hemisphere
      to the left precentral gyrus participate in motor control, the observed
      cerebellar activation, thus, seems to be related to the articulatory level of
      speech production rather than, as suggested by previous PET studies, to cognitive
      operations.

PMID- 9655625
TI  - Changes in proton currents in murine microglia induced by cytoskeletal disruptive
      agents.
AB  - Voltage-gated proton currents (IPR) were investigated in cultured murine
      microglia using the whole-cell configuration of the patch clamp technique. At a
      gradient of 1.5 between intracellular (pHi = 6.0) and extracellular pH (pHo =
      7.5) values, outward IPR were detected at depolarizing potentials, while the
      activation threshold of IPR was -40 mV. Time-dependent activation of IPR was
      fitted by a single exponential with a time constant of 661 ms at +40 mV. An
      increase in the activation time constant of IPR was seen after exposure of
      microglia to the cytoskeletal disruptive agents cytochalasin D or colchicine.
      Moreover, the current density of IPR was significantly reduced by 49% in cells
      treated with cytochalasin D and by 27% in cells treated with colchicine for 24 h.
      In contrast, voltage-dependence of steady-state activation of IPR was unchanged
      after disruption of the cytoskeleton. Exposure of microglia to the cytoskeletal
      stabilizers phalloidin and taxol did not affect IPR of microglia.

PMID- 9655626
TI  - Serum levels of macrophage-derived protein MRP-8/14 are elevated in active
      multiple sclerosis.
AB  - Serum concentrations of two macrophage-derived calcium-binding proteins, MRP-8
      and MRP-8/14, were studied in 28 patients with relapsing multiple sclerosis (MS).
      Serum levels were determined with a commercially available sandwich ELISA and the
      one-tailed Mann-Whitney U test was used for statistical analysis. Median serum
      levels of MRP-8/14 were significantly higher in MS patients (5150 ng/ml) compared
      to 26 healthy controls (1482 ng/ml) and significantly higher in MS patients
      within an acute relapse (6690 ng/ml) compared to MS patients with stable disease
      (3050 ng/ml). MRP-8 levels were not elevated in MS patients. These results may
      indicate an early activation of macrophages in the formation of demyelinating MS
      plaques. In addition, increased serum levels of MRP-8/14 may prove to be a useful
      paraclinical disease activity parameter in MS patients.

PMID- 9655627
TI  - Cancellation of low-frequency stimulation-induced long-term depression by
      docosahexaenoic acid in the rat hippocampus.
AB  - The effects of docosahexaenoic acid (DHA) on low-frequency stimulation (LFS)
      induced long-term depression (LTD) were investigated in the CA 1 subfield of rat
      hippocampal slices. LTD was routinely produced by LFS of 900 pulses at 1 Hz. The
      field excitatory postsynaptic potential (fEPSP) 40 min after LFS was 59 +/- 4% (n
      = 18) of baseline response. However, in experiments from 18 neurons pretreated
      with DHA (50 microM), fEPSP returned to baseline levels within 20 min after LFS
      in eight cells and was slightly potentiated in three cells. Only in seven cells
      was LTD induced. The effect of DHA on LTD was concentration dependent. The slopes
      of fEPSP 40 min after LFS were 67 +/- 4% (n = 6), 72 +/- 7% (n = 7) and 80 +/- 5%
      (n = 18) of baseline response, with pretreatment of 1, 10 and 50 microM DHA,
      respectively. The blockade of LTD induction suggests that DHA may play a role in
      learning and memory.

PMID- 9655628
TI  - Comparison of mitochondrial respiratory chain enzyme activities in rodent
      astrocytes and neurones and a human astrocytoma cell line.
AB  - This study has found that mitochondrial NADH-CoQ1 reductase (complex I) activity
      is significantly lower in C57 mice astrocytes compared with Wistar and Sprague
      Dawley rat astrocytes, and a human astrocytoma cell line. In addition, complex I
      activity is 4-fold greater in Sprague-Dawley neurones when compared to Wistar or
      C57 neurones. These findings have important implications for mitochondrial
      studies involving rodent or human cell line systems, and in particular, indicate
      the importance of choosing an appropriate model when investigating the
      mitochondrial respiratory chain.

PMID- 9655629
TI  - Motor denervation induces altered muscle fibre type densities and atrophy in a
      rat model of neuropathic pain.
AB  - Loose ligation of a sciatic nerve in rats (chronic constriction injury; CCI)
      provokes sensory, autonomic, and motor disturbances like those observed in humans
      with partial peripheral nerve injury. So far, it is unknown whether these motor
      disturbances result from (mechanical) allodynia or from damage to the motor
      neuron. These considerations prompted us to assess, in CCI rats, the density of
      motor axons in both the ligated sciatic nerve and the ipsilateral femoral nerve.
      To this end, we determined the number of cholinesterase positive fibres. It has
      been demonstrated previously that muscle fibre type density may be used as a
      measure of motor denervation and/or hypokinesia. Therefore, the myofibrillar
      ATPase reaction was employed to assess fibre type density in biopsies obtained
      from the lateral gastrocnemius muscle (innervated by sciatic nerve) and rectus
      femoris muscle (innervated by femoral nerve). We observed axonal degeneration of
      motor fibres within the loosely ligated sciatic nerve, both at an intermediate
      (day 21) and at a late stage (day 90) after nerve injury. The reduction in the
      number of motor nerve fibres was more pronounced distal to the site of the
      ligatures than proximal. A (less pronounced) reduction of motor fibres was
      observed in the ipsilateral (non-ligated) femoral nerve. In line with these
      findings, we observed altered fibre type densities in muscle tissue innervated by
      the ligated sciatic nerve as well as the non-ligated femoral nerve indicative of
      motor denervation rather than hypokinesia. The findings of this study suggest
      that the motor disorder induced by partial nerve injury involves degeneration of
      motor nerve fibres not only within the primarily affected nerve but also within
      adjacent large peripheral nerves. This spread outside the territory of the
      primarily affected nerve suggests degeneration of motor neurons at the level of
      the central nervous system.

PMID- 9655630
TI  - Dysphonia, an uncommon symptom of systemic neurotoxic envenomation by Vipera
      aspis bite. Report of two cases.
AB  - Two cases of Vipera aspis bites with severe envenomation in which, among other
      neurotoxic signs, dysphonia was observed, with alteration of the pitch of the
      voice are described. This uncommon symptom has never been reported in
      envenomation by European adders. It is pointed out that bites of European vipers
      should never be underestimated as severe envenomation may develop.

PMID- 9655631
TI  - Gating and permeability of ion channels produced by botulinum toxin types A and E
      in PC12 cell membranes.
AB  - Botulinum neurotoxin (BoNT) is known to produce cationic channels in artificial
      bilayers. This study examined ion channels formed by BoNT in native membranes
      from cultured PC12 cells under conditions approximating those thought to occur
      during toxin internalization. Membrane patches were excised from PC12 cells using
      patch electrodes and exposed to symmetrical solutions containing either 200 mM
      CsCl, RbCl or KCl. The patch pipettes also contained 1-5 microg/ml BoNT buffered
      to pH 5.3 while the bath solutions were buffered to pH 7.0. In the presence of
      toxin, bursts of ion channel openings were observed. These toxin-induced channels
      were most active with a negative voltage applied to the same side as the toxin
      (cis). The increased activity at negative voltages was due to an increase in mean
      open time of e-fold per 120 mV and a decrease in mean closed time between bursts
      of e-fold per 110 mV. The shorter mean closed time within a burst was independent
      of membrane voltage. While BoNT-induced ion channels started as a single
      conductance level of 27 pS (KCl), 34 pS (RbCl) or 46 pS (CsCl) they typically
      increased in roughly equal steps to five or more times the original channel
      conductance. These higher conductance BoNT 'channels' opened and closed
      synchronously and could be distinguished from superposition of multiple
      independent channels. Despite differences in putative transmembrane sequences
      between BoNT/A and BoNT/E, both serotypes evidenced the same channel conductance
      and mean open time.

PMID- 9655632
TI  - Enkephalin-processing oligopeptidases in cobra venom: inhibition by thiorphan and
      bestatin reveals co-operative actions.
AB  - The peptidase inhibitors thiorphan and bestatin were tested for their ability to
      inhibit the actions of the oligopeptidases contained in the venom of the Taiwan
      cobra (Naja naja atra). With methionine enkephalin (TyrGlyGlyPheMet) as
      substrate, thiorphan was an effective inhibitor of cleavage of the GlyPhe peptide
      bond while bestatin inhibited cleavage of the TyrGly peptide bond. Thiorphan and
      bestatin also inhibited subsequent cleavage of the fragments GlyGlyPheMet and
      TyrGlyGly respectively. These inhibitors reveal an interplay between the venom
      oligopeptidases in which the enzymes provide additional substrates for each other
      following their initial competitive attack on the neuropeptide. A possible
      explanation is that the system is intended to ensure a steady release of Tyr,
      GlyGly and PheMet over time. Significantly, Tyr is the favoured substrate of the
      L-amino acid oxidase present in the venom, which rapidly transforms this aromatic
      amino acid into phenolic derivatives. The efficacies of these inhibitors also
      suggest that there are similarities between the venom oligopeptidases and the
      peptidases associated with the processing of enkephalin in its normal contexts.

PMID- 9655633
TI  - A case of intestinal infarction following Vipera aspis bite.
AB  - A case of Vipera aspis bite followed by severe envenomation, shock, neurotoxic
      symptoms, myoglobinuria and coagulation disorders with thrombosis of the iliac
      vessels and intestinal infarction is described. A right hemicolectomy had to be
      performed. Treatment is described in detail. European adder bites may cause,
      although uncommonly, severe envenoming with unusual symptoms. The attending
      doctor must be prepared to face unusual diagnostic and therapeutic problems.

PMID- 9655634
TI  - Differential neurotoxicity of etorphine-like opiates: lack of correlation with
      their ability to activate opiate receptors.
AB  - The present study was undertaken to compare the neurotoxic effects of three
      etorphine-like opiates (etorphine, dihydroetorphine, and another derivative of
      oripavine) and heroin with their ability to activate opiate receptors in human
      neuroblastoma cell line SK-N-SH as well as in two other neuronal cell lines.
      Neurotoxicity was measured by using [3H]-thymidine incorporation analysis, cell
      viability measurement and Cytosensor microphysiometry. It was found that, in
      spite of the very similar molecular structures of these opiates, they displayed
      significant differences in cytotoxicity, with etorphine and another derivative of
      oripavine possessing high potency but dihydroetorphine and heroin little effect.
      However, neurotoxic potency of the opiates was not directly correlated to their
      ability to activate opioid receptors, as determined by [35S]-guanylyl-5'-O-(gamma
      tho)-triphosphate binding assay. These findings provide clear evidence of
      differential neurotoxicity of etorphine-like opiates, and suggest that the
      neurotoxicity is not closely related to the molecular configuration required as
      opioid receptor agonist but is probably associated with the presence of a double
      bond in the structure.

PMID- 9655635
TI  - Purification from Bothrops lanceolatus (fer de lance) venom of a
      fibrino(geno)lytic enzyme with esterolytic activity.
AB  - Bothrops lanceolatus venom has high caseinolytic, phospholipasic, esterolytic and
      hemorrhagic activities. In spite of having no coagulant effect on plasma, this
      venom contains a thrombin-like enzyme. Using gel filtration and ion-exchange
      chromatographies, we have purified an esterolytic fraction (F-II-1a) from this
      venom with a protein yield of 4% and a 58% recovery in enzyme activity. SDS-PAGE
      in the presence of beta-mercaptoethanol showed that the enzyme is a single chain
      polypeptide with a MW=38,100. Immunodiffusion and immunoelectrophoresis of
      fraction F-II-1a against serum from horses immunized with B. lanceolatus venom
      and against rabbit antiserum prepared using fraction F-II-1a both showed a single
      immunoprecipitin line. The Km and Vmax values for TAME hydrolysis were 0.85 mM
      and 38.6 micromol/min/mg, respectively. The esterolytic activity was completely
      inhibited by PMSF (10 mM) but not by EDTA (20 mM). Fraction F-II-1a hydrolyzed
      the alpha and beta chains of fibrinogen. Degradation of the alpha chain occurred
      within 10 min while that of the beta-chain was slower. The enzyme had no effect
      on the gamma-chain even after 4 h of hydrolysis.

PMID- 9655636
TI  - Two similar peptides from the venom of the scorpion Pandinus imperator, one
      highly effective blocker and the other inactive on K+ channels.
AB  - Two novel peptides, named Pi4 and Pi7, were purified from the venom of the
      scorpion Pandinus imperator, and their primary structures were determined. These
      peptides have 38 amino acids residues, compacted by four disulfide bridges,
      instead of the normal three found in most K+-channel specific toxins. Both
      peptides contain 25 identical amino acid residues in equivalent positions (about
      66% identity), including all eight half-cystines. Despite the fact that their C
      terminal sequence comprising amino acid residues 27 to 37 are highly conserved
      (10 out of 11 amino acids are identical), Pi4 blocks completely and reversibly
      Shaker B K+ -channels (a Kv1.1 sub-family type of channel) at 100nM
      concentration, whereas Pi7 is absolutely inactive at this concentration. Similar
      effects were observed in binding and displacement experiments to rat brain
      synaptosomal membranes using 125I-Noxiustoxin, a well known K+-channel specific
      toxin. In this preparation Pi4 displaces the binding of radiolabeled Noxiustoxin
      with Ic50 in the order of 10 nM, whereas Pi7 is ineffective at same
      concentration. Comparative analysis of Pi4 and Pi7 sequences with those obtained
      by site directed mutagenesis of Charybdotoxin, another very well studied K 
      channel blocking toxin, shows that the substitution of lysine (in Pi4) for
      arginine (in Pi7) at position 26, might be one of the important 'point mutations'
      responsible for such impressive variation in blocking properties of both toxins,
      here described.

PMID- 9655637
TI  - Pharmacological aspects of mouse hind-paw oedema induced by Lachesis muta
      rhombeata venom.
AB  - Pharmacological aspects of mouse hind-paw oedema induced by subplantar injections
      of Lachesis muta rhombeata (LMR) venom were investigated. The oedema induced by
      subplantar injections of 10 to 50 ng/g of LMR venom is dose dependent, with
      onset, peak and duration at 30, 60 and 180 min, respectively. Subplantar
      injection of 30 ng/g of Bothrops jararaca (BJ) venom induced oedema that has the
      same intensity as 30 ng/g of LMR venom but lasts for more than 4 h suggesting
      different time course. Systemic effects or haemorrhage were not observed with
      doses less than 50 ng/g. Oedema is not due to the presence of oedematogenic
      amines since dialysis did not change the oedema induced by 30 ng/g of LMR venom.
      Part of the oedema induced by LMR venom is due to a thermolabile fraction since
      pre-heating the venom at 100 degrees C for 15 min induced a significant reduction
      (56.19 +/- 6.8%) of the oedematogenic activity. The oedema induced by LMR venom
      is possibly induced by release of a pharmacological active substance at the site
      of injection. Histamine, arachidonate metabolites, nitric oxide and serotonin may
      play important roles in the oedematogenic effect of LMR venom since pre-treatment
      of mice with pyrilamine, indomethacin, dexamethasone, L-NAME and methysergide
      induced a significant reduction (49.86 +/- 10%; 51.06 +/- 5.9%; 77.66 +/- 3.6%;
      73.30 +/- 6.1% and 93.77 +/- 2.8%, respectively) of the oedema formation. The
      present results demonstrate that the oedema induced by LMR and BJ venoms may be
      triggered and maintained by different pharmacological mechanisms. Since
      methysergide and L-NAME were the most active inhibitors of the oedema we can
      suggest that a link between serotonin release by the venom and a NO synthase
      activation may be an important step in the oedema formation induced by LMR venom.

PMID- 9655638
TI  - Purification of haemorrhagic proteinase from the venom of Agkistrodon caliginosus
      (Kankoku-Mamushi).
AB  - A haemorrhagic proteinase was purified from A. caliginosus venom by ion-exchange
      chromatography on CM-Sephadex C-50, DEAE-Sephadex A-50, S-Sepharose Fast Flow and
      Q-Sepharose Fast Flow, and gel-filtration on a Sephadex G-100 column. By this
      procedure, about 17.6 mg of the enzyme were obtained from 4 g of the venom. The
      enzyme showed a single band on polyacrylamide gel electrophoresis at pH 8.3 and
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme had weak
      caseinolytic and potent haemorrhagic activities, and the minimum haemorrhagic
      dose of the enzyme was about 0.04 microg. The haemorrhagic activity of the enzyme
      was only suppressed by treatment with ethylenediamine tetraacetic acid-disodium
      or o-phenanthroline. The enzyme is composed of a single polypeptide chain with a
      molecular weight of about 70 kDa and is a glycoprotein. These results indicate
      that the enzyme is a metalloproteinase as are haemorrhagic proteinases from other
      snake venoms.

PMID- 9655639
TI  - Enzyme and biochemical studies of stonefish (Synanceja trachynis) and soldierfish
      (Gymnapistes marmoratus) venoms.
AB  - Venoms from the scorpaeniformes Synanceja trachynis and Gymnapistes marmoratus
      were quantitatively analyzed for enzymic activity. S. trachynis venom displayed
      significantly higher hyaluronidase activity than G. marmoratus venom, and G.
      marmoratus venom displayed significantly higher levels of esterase, acid
      phosphatase, alkaline phosphatase and phosphodiesterase activity. No detectable
      quantities of phospholipase A2 activity were found in G. marmoratus venom. SDS
      polyacrylamide gel electrophoresis of S. trachynis venom indicated the presence
      of 6 protein bands (20 kDa-295 kDa). G. marmoratus venom displayed 8 protein
      bands (11 kDa-109 kDa).

PMID- 9655640
TI  - Tigloylcholine: a new choline ester toxin from the hypobranchial gland of two
      species of muricid gastropods (Thais clavigera and Thais bronni).
AB  - Crude extracts from hypobranchial glands of two species of muricid gastropods,
      Thais clavigera and Thais bronni, were highly lethal to mice. Regardless of
      species, a new choline ester was isolated as the major toxic principle and
      elucidated to be tigloylcholine, a structural isomer of senecioylcholine widely
      found in gastropod hypobranchial glands, by 1H- and 13C-NMR as well as FAB-MS.
      The i.v. LD50 (mouse) of tigloylcholine was estimated to be 0.92 mg/kg.

PMID- 9655641
TI  - Paralytic toxins in Taiwanese starfish Astropecten scoparius.
AB  - Paralytic toxicity was seasonally detected in every 10 specimens of the starfish
      Astropecten scoparius from Pingtung in Taiwan from December 1995 to November
      1996. The highest toxicity and the average toxicity of total specimens, expressed
      as tetrodotoxin (TTX), were 5,938 and 1,679 mouse unit (MU), respectively. The
      highest value of monthly average toxicity in viscera and other parts were 354 and
      247 MU/g, respectively. The toxin was partially purified by YM-2 membrane
      ultrafiltration and Bio-Gel P-2 column chromatography. HPLC and GC-MS analyses
      showed that the starfish toxin was mainly composed of tetrodotoxin (88%), along
      with minor gonyautoxin 2-3 and saxitoxin (12%).

PMID- 9655642
TI  - Tourniquet ineffectiveness to reduce the severity of envenoming after Crotalus
      durissus snake bite in Belo Horizonte, Minas Gerais, Brazil.
AB  - Clinical and laboratory data from patients who applied a tourniquet (tourniquet
      group, n = 45) and who did not apply it (non-tourniquet group, n = 52) after
      being bitten by Crotalus durissus were compared. The patients were treated with
      100-200 ml of Crotalus durissus antivenom. The gender, age, time elapsed between
      bite and hospital admission, dose of antivenom and the frequency of local
      paresthesia, myalgia and palpebral ptosis did not differ between the two groups.
      Plasma creatine kinase enzyme activity and partial thromboplastin time, plasma
      whole venom and crotoxin concentrations and the frequency of acute renal and
      respiratory failure and number of deaths also did not differ between both groups.
      Data from this study show the ineffectiveness of tourniquet applied by patients
      in the fields to reduce the severity of Crotalus durissus envenoming.

PMID- 9655643
TI  - Envenomation of mice by Thai cobra (Naja kaouthia) venom: tolerable venom
      concentration and exposure time.
AB  - Naja kaouthia venom appeared in circulation rapidly after intramuscular injection
      into mice. The venom concentration attained a maximum level with all doses
      examined after 20 min. The half value of the maximum level was obtained 1 min
      after injection when a dose of 4LD50 was used. A critical venom concentration
      endangering mice was assessed from venom concentration in the sera of mice
      envenomed with sublethal dose (LD50). A fatal condition was produced within 30
      min at a venom concentration of 200-300 ng/ml or within 50 min at a venom
      concentration of 100-150 ng/ml.

PMID- 9655644
TI  - Influence of gossypol on the secretory function of cultured rat sertoli cells.
AB  - Cottonseed gossypol is a potent male contraceptive in several mammalian species
      including man. Sertoli cells play a crucial role in spermatogenesis. Therefore,
      the antifertility competence of gossypol may reflect a change in Sertoli cell
      function. Rat primary cultures were used to examine the effect of gossypol on
      cell viability, mitochondrial dehydrogenase function, lactate production and
      secretion of the Sertoli cell-specific protein inhibin. Exposure for 24 h to
      gossypol (3-6 microM) significantly enhance secretion of lactate but reduce
      secretion of inhibin without affecting cell viability. At 9-15 microM, the
      observed decrease of both lactate and inhibin accumulation apparently resulted
      from Sertoli cell degeneration and death, because viability and mitochondrial
      function were also reduced. The results suggest that mitochondria of Sertoli
      cells are a possible target for gossypol-induced infertility.

PMID- 9655645
TI  - Bibliography of toxinology.

PMID- 9655646
TI  - Angiotensin II antagonists: efficacy, duration of action, comparison with other
      drugs.
AB  - The benefits of anti-hypertensive drug treatment have been established by
      clinical trials demonstrating significant reductions in cardiovascular morbidity
      and mortality. Thiazide diuretics predominated in these trials but it is
      reasonable to conclude that the benefits were attributable to the blood pressure
      (BP) reduction per se and not to specific pharmacological characteristics.
      Furthermore, it can be calculated that even greater benefits would probably have
      accrued if the magnitude of the BP reduction had been greater. On first
      principles, therefore, the basic requirement for any anti-hypertensive drug is
      confirmation of its ability to reduce BP. The angiotensin II antagonists
      constitute an important new class of drug, with a low incidence of adverse
      effects, but early studies with the prototype, losartan, have raised some doubts
      about its anti-hypertensive 'potency' in the clinical setting. For example, in
      several different comparative studies there were consistently lesser BP
      reductions with losartan compared to enalapril. This applied to both the trough
      and peak BP reductions. Furthermore, dose-response relationships have not always
      been clearly defined: for example, in one study diastolic BP reductions (trough)
      fell in the range 4.1 to 4.8 mm Hg with 50, 100 and 150 mg losartan. Although the
      preliminary results with newer angiotensin II antagonists suggest that they may
      have greater efficacy, there is only limited information about the definitive
      identification of the clinically relevant dose ranges for many of these drugs.

PMID- 9655647
TI  - Molecular and cellular mechanisms of action of angiotensin II (AT1) receptors in
      vascular smooth muscle.
AB  - Angiotensin is an important regulator of blood pressure and exerts both pressor
      actions and influences growth in the cardiovascular system via the AT1 receptor.
      This review describes a number of signalling mechanisms involved in
      vasoconstriction and growth in response to AT1 receptor activation in vascular
      smooth muscle.

PMID- 9655648
TI  - The potential role of angiotensin II in the vasculature.
AB  - Arterial hypertension is associated with marked changes in the structure of both
      resistance and large arteries. The renin-angiotensin system is largely involved
      in these alterations; chronic blockade of the renin-angiotensin system prevents
      and/or reverses most of the alterations of the vasculature in experimental and
      clinical hypertension. In this review we have analysed the differential role of
      AT1 and AT2 receptors in the response of the vessels to arterial hypertension. It
      emerges that the relative involvement of each receptor depends on cell type, the
      studied specie, and experimental condition. Several points must be investigated
      in the near future, and especially: (1) the precise role of angiotensin receptors
      in different cell types and different stages of differentiation; (2)the
      transduction pathway used by the AT2 receptor in different cell types; (3) the
      possible interactions between the two receptor subtypes; and finally, (4) a
      possible role of (a) new subtype(s) of angiotensin II receptor.

PMID- 9655649
TI  - Bioactive angiotensin peptides.
AB  - Angiotensin II is recognised as the principle active peptide of the renin
      angiotensin system, exerting effects on fluid and electrolyte homeostasis, and
      cardiovascular control including neural and long term trophic effects. However,
      recent studies indicate that other angiotensin peptides such as angiotensin III,
      angiotensin II (1-7) and angiotensin IV, may have specific actions.
      Interestingly, recent work involving angiotensin IV demonstrates that this
      peptide binds to specific receptors and may be involved in memory retention and
      neuronal development. Furthermore, our demonstration that a globin fragment, LVV
      haemorphin-7, binds with high affinity to the angiotensin IV binding site and is
      abundant in the brain, indicates that this may represent a novel brain
      neuropeptide system. It now appears, that the renin-angiotensin system is more
      complex than previously thought and capable of generating multiple, active
      peptides which elicit numerous diverse actions.

PMID- 9655650
TI  - The importance of the renin-angiotensin system in cardiovascular disease.
AB  - The renin-angiotensin system is central to the pathophysiology of a number of
      cardiovascular disorders. Most obviously this is so with renin secreting tumours,
      but the system is of central importance in other disorders such as scleroderma
      renal crisis and most cases of malignant hypertension. Activation of the renin
      angiotensin system in unilateral renal artery stenosis is pivotal to the
      development of hypertension and the disturbances in electrolyte and volume
      balance -- most particularly in the hyponatraemic-hypertensive syndrome.
      Likewise, stimulation of the renin-angiotensin system is an important
      contributor, amongst many other systems, to the pathophysiology of cardiac
      failure. In diabetic nephropathy, the renin-angiotensin system is often
      suppressed as gauged by circulating levels of renin, yet it appears to make an
      important contribution to the progressive decline in renal function. Much less
      clear is the role of the renin-angiotensin system in essential hypertension
      insofar as it contributes to the level of blood pressure, to the development of
      left ventricular hypertrophy, and in the evolution of complications such as
      stroke and myocardial infarction. Blockade of the renin-angiotensin system with
      angiotensin-converting enzyme inhibitors has contributed to our understanding of
      the role of this system in cardiovascular disease. The advent of selective
      angiotensin II type-1 receptor blockers will further increase knowledge in this
      area.

PMID- 9655651
TI  - Angiotensin AT1 receptor antagonism and protection against cardiovascular end
      organ damage.
AB  - This review describes how angiotensin AT1 receptor antagonists (eg, candesartan
      cilexetil, losartan) effectively protect against end-organ damage including
      stroke, cardiac hypertrophy, renal dysfunction, glomerulosclerosis, and/or
      vascular hypertrophy in the models of stroke-prone spontaneously hypertensive
      rats (SHRSP), SHR, DOCA/salt hypertensive rats, Dahl hypertensive rats and/or 5/6
      nephrectomised rats. Particularly in SHRSP and DOCA/salt hypertensive rats,
      candesartan cilexetil markedly reduced the incidence of stroke and renal injury
      even at doses which had no effect on blood pressure (BP), suggesting that the
      tissue protective effects of angiotensin AT1 antagonists are not attributable
      simply to the normalisation of BP. In the heart, kidney and vascular tissues of
      SHRSP and the kidney of DOCA/salt hypertensive rats, the mRNA levels for
      transforming growth factor (TGF)-beta1 and extracellular matrix components
      (fibronectin, collagen type I, III and IV and laminin) were increased, and the
      increases of the gene expression were inhibited by treatment with candesartan
      cilexetil. In addition, there are some reports indicating that angiotensin AT1
      receptor antagonists inhibit directly hypertrophy or proliferation of cultured
      cardiac myocytes and nonmyocytes (fibroblast), cultured mesangial cells and
      cultured vascular smooth muscle cells, which were stimulated by angiotensin II.
      These in vitro and in vivo findings suggest that local tissue AT1 receptor
      stimulation, being accompanied by the increased gene expression of TGF-beta1 and
      extracellular matrix components may partially contribute to the pathogenesis of
      cardiovascular end-organ damage.

PMID- 9655652
TI  - Receptors and their classification: focus on angiotensin II and the AT2 receptor.
AB  - Angiotensin II mediates its effects through angiotensin receptors. The use of
      specific angiotensin receptor ligands and the cloning of these receptors allows
      their classification. So far, the AT1, AT2 and atypical angiotensin II receptors
      are recognised. The AT1 receptor is responsible for the classical effects of the
      renin-angiotensin system such as vasoconstriction, renal salt and water
      retention, central osmo-control and stimulation of cell growth. The function of
      the AT2 receptor is far from clear but this receptor appears to be important in
      fetal development, cell growth inhibition and differentiation processes. This
      review describes the angiotensin receptors and focuses on the possible functions
      of the AT2 receptor.

PMID- 9655653
TI  - Postmenopausal hormone replacement therapy in hypertensive women: is it time for
      a change in attitude?

PMID- 9655654
TI  - Transdermal oestrogen reduces daytime blood pressure in hypertensive women [see
      comment].
AB  - The aim of this study was to investigate the acute effects of transdermally
      administered 17-beta-oestradiol on ambulatory blood pressure (BP) in
      hypertensive, postmenopausal women. Thirteen postmenopausal women with ongoing
      treatment for hypertension were included in this placebo-controlled, double-blind
      cross-over study. Ambulatory recordings of BP and heart rate were performed
      during 24 h on two occasions, separated by at least 1 week, after application of
      a patch containing either 100 microg per 24 h 17-beta-oestradiol or placebo.
      Serum oestradiol was increased (P<0.001) during active treatment (139.2 +/- 21.1
      pg/ml) compared with the baseline postmenopausal levels recorded during placebo
      (40.5 +/- 2.2 pg/ml). No rise in BP was found in office BP or during ambulatory
      recordings. Daytime BP pressure was acutely reduced by approximately 3 mm Hg
      during the 24 h of treatment with oestrogen (SBP n.s., DBP P<0.05), without any
      change in heart rate. Nocturnal dipping in SBP and DBP was present during placebo
      conditions, and there were no signs of an increase in dipping during treatment
      with 17-beta-oestradiol. This study supports previous evidence that hormone
      replacement therapy is safe in hypertensive women. The data in the present study
      also imply an acute, but small reduction of daytime BP due to transdermal
      oestrogen in hypertensive, postmenopausal women. Furthermore oestrogen did not
      blunt or increase the dipping phenomena during the night in these women.

PMID- 9655655
TI  - Randomised comparison of percutaneous angioplasty vs continued medical therapy
      for hypertensive patients with atheromatous renal artery stenosis. Scottish and
      Newcastle Renal Artery Stenosis Collaborative Group.
AB  - BACKGROUND: Data from randomised studies are lacking on the value of
      interventional procedures in the management of atheromatous renal artery
      stenosis. This randomised prospective trial compared the effects on blood
      pressure (BP) and renal function of percutaneous transluminal angioplasty vs
      medical therapy in hypertensive patients with both unilateral and bilateral
      disease. METHODS: A total of 135 eligible patients were identified, of whom 55
      (44%) were randomised. Eligible patients had sustained hypertension, with a
      minimum diastolic BP of 95 mm Hg on at least two anti-hypertensive drugs. Renal
      artery stenosis was defined by renal angiography as at least 50% stenosis in the
      affected vessel. All patients were observed during an initial 4-week run-in
      period on a fixed drug regimen and subsequent changes measured from this 4-week
      baseline. RESULTS: Blood pressure fell during the run-in period in all groups. In
      patients with bilateral renal artery stenosis randomised to angioplasty, a
      statistically significant (P<0.05) fall in BP was observed at latest follow-up
      (range 3-54 months). The mean fall in BP at latest follow-up in the angioplasty
      group, corrected for the medical group response, was 26/10 mm Hg. In patients
      with unilateral renal artery stenosis, no statistically significant or clinically
      important differences in outcome were observed between the two groups. No
      significant differences or trends in serum creatinine were observed between or
      within any group during follow-up. Major outcome events (death, myocardial
      infarction, heart failure, stroke, dialysis) were similar in the angioplasty and
      medical groups during follow-up. In the 40/135 patients undergoing angioplasty,
      serious or potentially serious complications attributable to the procedure were
      observed in 11 patients, bleeding at the arterial site (8 patients) being the
      most frequent. CONCLUSIONS: In hypertensive patients with atheromatous renal
      artery stenosis, percutaneous renal angioplasty results in a modest improvement
      in systolic BP compared with medical therapy alone. This benefit was confined to
      patients with bilateral disease. No patient was 'cured', renal function did not
      improve, and intervention was accompanied by a significant complication rate.

PMID- 9655656
TI  - The prevalence of silent myocardial ischaemia in patients with white-coat
      hypertension.
AB  - The aim of this study was to estimate the incidence of silent myocardial
      ischaemia in patients with mild to moderate hypertension, white-coat hypertension
      (WCH) and those with normal blood pressure. Ambulatory electrocardiographic (ECG)
      monitoring was carried out in 272 cases with normal blood pressure, 164 cases
      with mild to moderate hypertension (diastolic blood pressure >95 and <114 mm Hg),
      and 106 cases with white-coat hypertension who were diagnosed with ambulatory
      blood pressure monitoring. The ages of the patients of all groups were between 42
      61 years. There were no differences between the groups according to age, gender
      and other parameters. There were no anginal symptoms, and resting ECGs were in
      normal limits in all cases. The diagnosis of silent ischaemia was considered to
      be present if there was ST depression >2 mm/at least 120 sec in ambulatory ECG
      examination without angina or its equivalent cardiac symptoms. The incidence of
      silent ischaemia was 6.4%, 18.8%, and 26.2% in cases with normal blood pressure,
      WCH, and hypertension, respectively. The differences between groups were
      significant. It was concluded that WCH is not a benign condition, but shares some
      characteristics with essential hypertension.

PMID- 9655657
TI  - Chest radiograph in the evaluation of first time wheezing episodes: review of
      current clinical practice and efficacy.
AB  - OBJECTIVE: To evaluate the current clinical use and utility of chest radiographs
      (CXR) in the workup of pediatric patients with first time wheezing (FTW)
      episodes. SETTING: Urban children's hospital. DESIGN: Retrospective review of
      medical records of patients seen in the emergency department in 1994 with
      disposition diagnoses of asthma or reactive airways disease, bronchiolitis,
      pneumonia, congenital heart disease, congestive heart failure, or foreign body
      aspiration to identify those patients presenting with FTW episodes. METHODS:
      Clinical findings in FTW were compared in patients receiving a CXR (121, 41%) and
      those who did not (177, 59%). Comparisons were made between patients with a
      clinically significant CXR (CXR-pos) (29, 24%) and those without (92, 76%). CXR
      pos was defined as a CXR result which would be expected to alter patient
      management. Comparisons between groups were analyzed using the two-tailed
      Student's t test for continuous variables and the chi2 statistic for categorical
      data. The level of significance was determined at P < 0.05. RESULTS: Two hundred
      ninety-eight episodes of FTW were identified of 1984 patient charts reviewed.
      Patients receiving CXR differed from those who did not by being of a greater age
      (39 vs 20 months, P < 0.01), having lower pulse oximetry (89.7 vs. 92.7%, P <
      0.01), being less likely to have a family history of asthma (47.5 vs 63.2%, P <
      0.01), or history of atopy (40.6 vs 59.4%, P < 0.01). Those with localized
      wheezes (59.4 vs 40.6% P < 0.01), localized rales (59.3 vs 40.7 % P < 0.01), and
      localized decreased breath sounds (59.3 vs 40.7%, P = 0.01) were also more likely
      to receive a CXR. Among patients receiving CXR, clinical characteristics
      associated with CXR-pos were elevated temperature (37.9 vs 37.5 degrees C, P =
      0.04), absence of family history of asthma 72.6 vs 27.4%, P < 0.01), and the
      presence of localized wheezes (76.0 vs 24.0%, P = 0.02), or localized rales (76.0
      vs 24.0%, P < 0.01). CONCLUSIONS: Clinicians in this setting do not routinely
      obtain a CXR in patients with FTW episodes. Retrospective examination of
      clinician practice revealed several clinical characteristics that were associated
      with increased use of CXR in FTW. Increased utility of the CXR was associated
      with patients having elevated temperature, an absence of a family history of
      asthma, and localized wheezes or rales by ausculatory examination.

PMID- 9655658
TI  - Clinical criteria for using radiography for children with acute knee injuries.
AB  - OBJECTIVE: To evaluate clinical criteria for selective radiography for knee
      injuries in children. DESIGN: Retrospective chart review. SETTING: Emergency
      department (ED) of a children's hospital. PARTICIPANTS: All patients evaluated by
      radiography for an isolated, acute knee injury during 12 months. Patients were
      excluded for injuries: >1 week; isolated to superficial lacerations/abrasions;
      with prior knee surgery; being reassessed. RESULTS: Two hundred fifty-four
      patients (60% male; 12.7 years median age) were included. Twelve patients (4.7%)
      sustained a fracture. Evaluated criteria were point tenderness, inability to bear
      weight in the ED, and inability to flex the knee to 90 degrees. Point tenderness
      was not statistically associated with fracture, P = 0.7. Inability to bear weight
      in the ED (37% fracture rate, P = 0.001) and inability to flex to 90 degrees (52%
      fracture rate, P < 0.001) were associated with the presence of fracture.[table in
      text] Applying a rule combining nobearwt and noflex90 would decrease the number
      of x-rays by 73%, with no missed fractures. CONCLUSIONS: Point tenderness was not
      a good predictor of knee fracture in children. Using the clinical criteria to
      select patients requiring knee radiography may greatly reduce the number of
      unnecessary x-rays.

PMID- 9655659
TI  - The childhood air gun: serious injuries and surgical interventions.
AB  - OBJECTIVE: Increasingly powerful nonpowder firearms or air guns are frequently
      given to children as toys. We undertook the present study to evaluate the
      injuries caused by these firearms, based on the concern that they are capable of
      inflicting serious trauma. DESIGN: Descriptive, retrospective chart review.
      SETTING: Urban level I pediatric trauma center. PARTICIPANTS: The study included
      all children with injuries secondary to air guns who were admitted between July
      1988 and March 1995. MAIN OUTCOME MEASURES: Type of weapon, circumstances of
      injury, anatomic location of injury, injury severity, surgeries performed,
      morbidity. INTERVENTIONS: None. RESULTS: There were 42 admissions with a mean
      hospital stay of seven days (range 1 to 136 days). The average age was 10 years
      (range 1 to 23 years) with a median age of 11 years. There were 35 boys and 7
      girls. Twenty-nine of the 42 injuries were caused by a family member or friend
      and five were self-inflicted. The mean injury severity score was 8.3. While there
      were no fatalities, 21 children (50%) underwent operative procedures for their
      injuries. Ten of the injuries were potentially lethal, of which seven were due to
      the "pump" action air gun. Sixteen patients had serious long-term disability as a
      result of their injuries. CONCLUSION: Air guns can cause a variety of serious
      injuries, often requiring operative intervention. The long-term morbidity from
      some of these injuries is significant. Both parents and physicians should be
      aware that nonpowder guns are not toys, but weapons capable of inflicting serious
      trauma. The evaluation and treatment of air gun injuries should be similar to
      that currently used for powder weapon injuries. Recommendations for evaluation
      and treatment are made.

PMID- 9655660
TI  - Use of Emergency Medical Service transport system in medical patients up to 36
      months of age.
AB  - OBJECTIVES: To determine the frequency of inappropriate transport by Emergency
      Medical Service (EMS). DESIGN: A retrospective study. SUBJECTS: Patients up to 36
      months of age with medical complaints transported by EMS to an urban pediatric
      emergency department (ED). INTERVENTIONS: None. MEASUREMENTS: Arbitrary criteria
      for appropriate use of EMS transport system were developed. The age, triage
      status, number of previous uses of EMS, health insurance status, time of calls,
      chief complaint, and clinical management of patients in the ED were determined.
      The frequency of inappropriate use of EMS was determined and also the percentage
      of patients up to 36 months of age who used EMS transport system on more than one
      occasion. RESULTS: Charts of 341 patients were reviewed of which 126 patients
      (37%) could have been transported by nonemergent vehicles according to our
      arbitrary criteria. In addition 97 (28%) of these patients had used the EMS
      transport system on at least one other occasion. CONCLUSIONS: EMS is utilized for
      inappropriate transportation in approximately 37% of our pediatric patients less
      than 36 months of age with medical complaints. In addition, 28% of these same
      patients utilized the EMS system on more than one occasion. It would appear that
      education of care providers in the appropriate use of EMS and use of alternate
      means of transportation would make the system more efficient and productive.

PMID- 9655661
TI  - Streptococcus pneumoniae bacteremia in children infected with HIV: presentation,
      course, and outcome.
AB  - OBJECTIVE: To examine the presentation, course, and outcome of pneumococcal
      bacteremia in children infected with human immunodeficiency virus (HIV). METHODS:
      A retrospective series of HIV-infected children less than 18 years of age with
      Streptococcus pneumoniae bacteremia from four urban, tertiary care hospitals was
      evaluated. The main outcome measures included persistent bacteremia, the
      development of a focal infection, and death. RESULTS: Seventy-two episodes of
      pneumococcal bacteremia were identified in 59 patients. Fifty-four first episodes
      were included; 26/54 were occult. Mean temperature was 39.8 degrees C. In
      patients with bacteremia, white blood cells (WBCs) > or = 15,000 and > or =
      10,000 had sensitivities of 40% and 75%, respectively. At the time of bacteremia,
      age >3 years old was associated with a lower mean WBC count compared with
      episodes occurring in patients <3 years old (11.2 vs 16.1, P < 0.05). Patients
      with occult bacteremia who were discharged with antibiotics (12 i.m., 7 p.o.)
      were less likely than patients without antibiotic treatment to have persistent
      bacteremia at a return visit within 72 hours (0/19 vs 2/5, P < 0.05). No patient
      with occult bacteremia died, progressed to clinical meningitis, or had other
      sequelae. Two of fifty-four patients died as a result of their first episode of
      invasive pneumococcal disease. Both patients who died had meningitis and appeared
      ill on initial presentation. CONCLUSIONS: Neither a WBC count > or = 15,000 nor >
      or = 10,000 is a sensitive indicator of pneumococcal bacteremia in HIV-infected
      children. Empiric antibiotics are useful to decrease the risk of persistent
      bacteremia. Children infected with HIV who have occult pneumococcal bacteremia
      appear to do well with appropriate antibiotics. Patients who are afebrile and
      well appearing on reevaluation may be safely treated as outpatients.

PMID- 9655663
TI  - Infant with epistaxis and absent femoral pulses.
AB  - Coarctation of the aorta is a congenital cardiac abnormality that can lead to
      congestive heart failure in early infancy or can go undetected for many years. We
      discuss the case of an infant who presented to our emergency department with
      epistaxis and was found to have this lesion based on the physical examination.
      The identification of this lesion before the onset of symptoms leads to improved
      survival in these patients. A cardiac murmur and differential blood pressure
      between upper and lower extremities are the most reliable physical findings for
      identifying patients with coarctation of the aorta. Absent femoral pulses are a
      hallmark of this lesion, but not a dependable finding.

PMID- 9655662
TI  - Physicians' attire as perceived by young children and their parents: the myth of
      the white coat syndrome.
AB  - OBJECTIVE: To determine if young children have a preference regarding whether
      physicians do or do not wear a white coat. METHODS: One hundred one children,
      ages four to eight years, and their parents were recruited from the outpatient
      setting of a pediatric referral center. Two pairs of photographs, the same man
      with and without a white coat and the same woman with and without a white coat,
      were shown to the children and their parents, and both were asked which of each
      pair they would like to have as their or their child's doctor, respectively.
      Parents filled out a questionnaire rating the appropriateness of various aspects
      of a physician's attire and appearance. RESULTS: The children selected the person
      in the white coat 69% of the time. The parents also selected the white coat more
      often (66%). On the questionnaire parents identified a name tag as the most
      appropriate item of dress followed by a white coat. A groomed mustache and
      groomed beard were also rated favorably. Open-toed sandals, clogs, and shorts
      were rated negatively, while parents were neutral with respect to hospital
      greens, blouse and skirt or dress, and shirt and tie. CONCLUSIONS: Physicians may
      wear a white coat without fear that they are negatively affecting their
      relationship with their pediatric patients four to eight years of age. The
      appropriateness of wearing a name tag is confirmed.

PMID- 9655664
TI  - Acute valproate ingestion induces symptomatic methemoglobinemia.
AB  - A wide variety of clinical outcomes have been described after acute valproate
      ingestion. We report for the first time the development of symptomatic
      methemoglobinemia after an acute ingestion of divalproex sodium (Depakote),
      resulting in serum concentrations 10 times greater than the therapeutic range.
      The methemoglobinemia was readily reversed with the administration of methylene
      blue. Valproate elimination was enhanced by the continuous infusion of activated
      charcoal. The patient recovered without permanent sequelae.

PMID- 9655665
TI  - Magnet-backed earrings: not just for decoration.

PMID- 9655666
TI  - Vaginal injury from a water slide in a premenarcheal patient.
AB  - BACKGROUND: Water under high pressure can produce vaginal injury. Previous
      reports suggest that postmenarcheal maturation and the presence of a vaginal
      foreign body contributed to water slide injuries in women. METHODS: A case of a
      vaginal injury from a water slide in a premenarcheal patient is presented. A
      literature review of water-related vaginal injuries in adults and children
      compares the mechanism of injury with that previously reported. RESULTS: The
      patient underwent operative repair of her injury. CONCLUSIONS: Vaginal injury in
      premenarcheal patients may result from a water slide. The emergency physician
      must be aware of this potential injury mechanism and the need for complete
      examination under anesthesia when vaginal bleeding is present.

PMID- 9655667
TI  - Acute hydrocephalus as a consequence of mumps meningoencephalitis.
AB  - Aqueductal stenosis can result from mumps meningoencephalitis. We report a case
      of acute hydrocephalus from an aqueductal stenosis developed immediately after a
      clinically evident mumps infection. The patient, aged two years, was treated with
      an antiedema therapy, and a ventriculoperitoneal shunt was placed. His clinical
      conditions rapidly improved. Only mumps virus was found in his cerebrospinal
      fluid culture. This case probably represents the earliest hydrocephalus from
      mumps, among those reported in the literature.

PMID- 9655668
TI  - Rickets presenting as seizures in the emergency department: medico-cultural
      implications.

PMID- 9655669
TI  - Reflex sympathetic dystrophy in children.
AB  - Reflex sympathetic dystrophy is becoming increasingly recognized in the pediatric
      population, yet there is very little about the disease in standard pediatric
      texts and nothing in the emergency medicine literature. Failure to diagnose
      Reflex sympathetic dystrophy in a timely fashion greatly decreases the likelihood
      of recovery. The diagnosis is primarily clinical. This report is intended to
      increase emergency physicians' awareness of this painful, disabling problem.

PMID- 9655670
TI  - Use of restraints in ambulances: a state survey.
AB  - PURPOSE: To determine the requirements in all states and the District of Columbia
      for use of restraints on patients in ambulances. MATERIALS AND METHODS: A
      structured telephone survey was conducted with all state Emergency Medical
      Services (EMS) agencies or the agency responsible for the regulation of
      ambulances. Questions were asked regarding restraint of patients in ambulances.
      The age definition of a pediatric patient was also queried. RESULTS: Ambulances
      are regulated in 47% of states by EMS, 14% by law enforcement, 3% by a public
      safety agency, and in some states by other agencies such as the Department of
      Motor Vehicles. In 27% of the states no agency is responsible for ambulance
      regulations. Most states do not require patients of any age to be restrained in
      ambulances; however, the drivers and passengers are required to wear seat belts.
      Most of the states with laws regulating ambulance restraints for infants and
      children were in the northeast. There is great variance in the age that defines a
      pediatric patient for EMS. CONCLUSION: A means of safely restraining infants and
      children in ambulances is needed. Until new restraints are available, ambulances
      should restrain infants and children in car seats and on gurneys. A national age
      standard for defining a pediatric patient using EMS is needed.

PMID- 9655671
TI  - Toxicology reviews: physostigmine.

PMID- 9655672
TI  - Four days of vomiting and diarrhea.

PMID- 9655673
TI  - Management problems: what to do and when to do it.

PMID- 9655674
TI  - Pediatric emergency medicine--legal briefs.

PMID- 9655675
TI  - Just another asthmatic? The many faces of asthma in pediatric transport.

PMID- 9655676
TI  - The use of propofol to treat status epilepticus in a nine-month-old female
      patient.

PMID- 9655677
TI  - G protein-coupled receptors in gastrointestinal physiology. IV. Neural regulation
      of gastrointestinal smooth muscle.
AB  - G protein-coupled receptors receive many of the neural, hormonal, and paracrine
      inputs to gastrointestinal (GI) smooth muscle cells. This article examines the
      major G protein-coupled receptors, G proteins, and effectors that mediate
      responses to enteric neuromuscular transmitters. Excitatory transmitters
      primarily couple through Gq/11 and Gi/Go proteins and elicit responses via
      formation of inositol trisphosphate and diacylglycerol and inhibition of adenylyl
      cyclase. Several inhibitory transmitters couple through Gs and activation of
      adenylyl cyclase. There are interesting examples, however, of inhibitory
      transmitters apparently using pathways regulated by Gq/11 to elicit responses by
      localized Ca2+ release and activation of Ca2+-dependent ion channels. G protein
      coupled receptors may also be differentially expressed by smooth muscle cells and
      interstitial cells of Cajal, which may increase the diversity of responses and
      allow specialized innervation of GI muscle tissues.

PMID- 9655678
TI  - Neural injury, repair, and adaptation in the GI tract. II. The elusive action of
      capsaicin on the vagus nerve.
AB  - Capsaicin is an excitotoxin for primary afferent neurons, and perivagal
      administration of capsaicin is frequently used to ablate afferent fibers from the
      vagus nerve in an attempt to elucidate the role of afferent fibers in
      gastrointestinal (GI) regulation. However, this method has recently been called
      into question by research demonstrating that the molecular target of capsaicin on
      spinal and trigeminal afferents, vanilloid receptor subtype 1 (VR1), is absent
      from vagal afferents. Although some concerns about selectivity exist, the
      available information suggests that perineural capsaicin defunctionalizes
      afferent neurons of the vagus nerve by acting on a vanilloid receptor subtype
      that is structurally different from VR1.

PMID- 9655679
TI  - Changes in methionine adenosyltransferase during liver regeneration in the rat.
AB  - Liver-specific and non-liver-specific methionine adenosyltransferase (MAT) are
      products of two genes (MAT1A and MAT2A, respectively) that catalyze the formation
      of S-adenosylmethionine (SAM), the principal methyl donor. We previously showed
      that MAT2A expression was associated with more rapid cell growth. Here we
      examined changes in hepatic MAT gene expression and related consequences after
      two-thirds partial hepatectomy (PH) in rats. The mRNA levels of both MAT forms
      increased from 3 to 6 h, but the MAT1A level then fell below baseline from 12 to
      24 h, whereas the MAT2A level remained elevated up to 4 days after PH. The
      increase in the MAT2A mRNA level was due to increased gene transcription and mRNA
      stabilization. The change in the MAT1A mRNA level was posttranscriptional and did
      not require de novo protein synthesis. Changes in MAT activity were consistent
      with an increased amount of MAT isozymes. SAM levels, the ratio of SAM to S
      adenosylhomocysteine (SAH), and DNA methylation fell from 6 to 24 h, whereas SAH
      levels increased slightly at 12 and 24 h after PH. Both increased SAM utilization
      and MAT2A gene expression likely contributed to the fall in SAM.

PMID- 9655680
TI  - Secretin inhibits gastric acid secretion via a vagal afferent pathway in rats.
AB  - Secretin is an enterogastrone that inhibits gastric acid secretion and motility.
      Recently, it was reported that secretin inhibited gastric emptying via a
      capsaicin (Cap)-sensitive vagal afferent pathway. However, a possible role of the
      sensory afferent pathway in secretin-inhibited acid secretion has not been
      clarified. We investigated whether or not the acid secretion suppressed by
      secretin is modulated by a vagal and/or splanchnic afferent pathway in rats.
      Subdiaphragmatic perivagal (PV) or periceliac ganglionic (PCG) application of Cap
      (10 mg/ml) or vehicle was performed in both conscious and anesthetized rats 2 wk
      before experiments. Bilateral vagotomy was performed in some conscious rats 5
      days before studies. Pentagastrin was administered intravenously at 0.6 microg .
      kg-1 . h-1. Secretin (20 pmol . kg-1 . h-1 iv) or 0.03 N HCl (4.32 ml/h id) was
      infused in conscious rats with gastric cannulas or anesthetized rats with
      ligation of the pylorus, respectively. A rabbit antisecretin serum was injected
      in some anesthetized rats before duodenal acidification. Secretin significantly
      inhibited pentagastrin-stimulated acid secretion by 63% (P < 0.01), which was
      abolished by both vagotomy and PV treatment of Cap in conscious rats. In
      anesthetized rats, duodenal infusion of 0.03 N HCl suppressed pentagastrin
      induced acid secretion by 59.4% (P < 0.01), which was reversed not only by
      antisecretin serum but also by PV application of Cap. However, PCG treatment with
      Cap did not influence the inhibition by secretin or duodenal acidification in
      either awake or anesthetized rats. These results indicate that the inhibition by
      secretin of pentagastrin-stimulated acid secretion is mediated by a Cap-sensitive
      vagal afferent pathway but not via a splanchnic afferent pathway in rats.

PMID- 9655681
TI  - CD4+ T cells mediate superantigen-induced abnormalities in murine jejunal ion
      transport.
AB  - The immunomodulatory properties of bacterial superantigens (SAgs) have been
      defined, yet comparatively little is known of how SAgs may affect enteric
      physiology. Staphylococcus aureus enterotoxin B (SEB) was used to examine the
      ability of SAgs to alter epithelial ion transport. BALB/c mice, severe combined
      immunodeficient (SCID, lack T cells) mice, or SCID mice reconstituted with
      lymphocytes or CD4+ T cells received SEB intraperitoneally, and jejunal segments
      were examined in Ussing chambers; controls received saline only. Baseline short
      circuit current (Isc, indicates net ion transport) and Isc responses evoked by
      electrical nerve stimulation, histamine, carbachol, or forskolin were recorded.
      Serum levels of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) were
      measured. SEB-treated BALB/c mice showed elevated serum IL-2 and IFN-gamma
      levels, and jejunal segments displayed a time- and dose-dependent increase in
      baseline Isc compared with controls. Conversely, evoked ion secretion was
      selectively reduced in jejunum from SEB-treated mice. Elevated cytokine levels
      and changes in jejunal Isc were not observed in SEB-treated SCID mice. In
      contrast, SCID mice reconstituted with T cells were responsive to SEB challenge
      as shown by increased cytokine production and altered jejunal Isc responses that
      were similar to those observed in jejunum from SEB-treated BALB/c mice. We
      conclude that exposure to a model bacterial SAg causes distinct changes in
      epithelial physiology and that these events can be mediated by CD4+ T cells.

PMID- 9655682
TI  - LPS receptor CD14 participates in release of TNF-alpha in RAW 264.7 and
      peritoneal cells but not in kupffer cells.
AB  - Lipopolysaccharide (LPS) is a bacterial polymer that stimulates macrophages to
      release tumor necrosis factor-alpha (TNF-alpha). In macrophages (RAW 264.7 and
      peritoneal cells), LPS binds to the CD14 surface receptor as the first step
      toward signaling. Liver macrophages, Kupffer cells, are the most numerous fixed
      tissue macrophage in the body. The presence of CD14 on Kupffer cells and its role
      in LPS stimulation of TNF-alpha were examined. TNF-alpha release by Kupffer cells
      after LPS stimulation was the same in the presence and absence of serum. RAW
      264.7 and peritoneal cells, which utilize the CD14 receptor, released
      significantly less TNF-alpha after LPS stimulation in the absence of serum
      because of the absence of LPS-binding protein. Phosphatidylinositol-phospholipase
      C treatment, which cleaves the CD14 receptor, decreased LPS-stimulated TNF-alpha
      release by RAW 264.7 cells but not by Kupffer cells. Deacylated LPS (dLPS)
      competes with LPS at the CD14 receptor when incubated in a ratio of 100:1
      (dLPS/LPS). Such competition blocked LPS-stimulated TNF-alpha release from RAW
      264.7 cells but not from Kupffer cells. Western and fluorescence-activated cell
      sorter analysis directly demonstrated the presence of CD14 on RAW 264.7 cells and
      murine peritoneal cells but showed only minimal amounts of CD14 in murine Kupffer
      cells. LPS stimulation did not increase the amount of CD14 detectable on mouse
      Kupffer cells. CD14 expression is very low in Kupffer cells, and LPS-stimulated
      TNF-alpha release is independent of CD14 in these cells.

PMID- 9655683
TI  - Altered sodium-hydrogen exchange activity is a mechanism for acid-induced
      hyperproliferation in Barrett's esophagus.
AB  - Acid produces a dynamic effect on the cell phenotype of Barrett's esophagus (BE)
      ex vivo. An acid pulse induces hyperproliferation, whereas continuous acid
      exposure promotes differentiation. To examine the mechanism for acid pulse
      induced hyperproliferation, we studied the Na+/H+ exchanger (NHE), which plays a
      role in the control of intracellular pH and cell proliferation. NHE was inhibited
      pharmacologically in endoscopic BE biopsies using amiloride analogs. Cell
      proliferation was assessed after pulsed or continuous acid exposure using
      tritiated thymidine incorporation assays and immunohistochemical analysis of
      proliferating cell nuclear antigen expression. The NHE-dependent intracellular pH
      response to an acid pulse was examined by pH-sensitive microfluorimetry using a
      Barrett's adenocarcinoma cell line TE7. NHE inhibition significantly reduced the
      hyperproliferative acid-pulse effect. Furthermore, the acid-pulse activation of
      NHE occurred via increased transporter activity (22Na uptake) without any change
      in NHE-1 protein levels. Inhibition of protein kinase C (PKC), an NHE activator,
      also reduced the hyperproliferative response. The response of TE7 cells to an
      acid pulse was similar to that of BE biopsies in terms of cell proliferation and
      NHE and PKC dependence. Acid-pulse exposure of TE7 cells resulted in
      intracellular acidification followed by reneutralization to an intracellular pH
      greater than preacidosis values. We conclude that NHE may mediate the
      hyperproliferative response of BE to an acid pulse via changes in intracellular
      pH.

PMID- 9655684
TI  - Identification of a domain in the carboxy terminus of CCK receptor that affects
      its intracellular trafficking.
AB  - The carboxy-terminal region of many guanine nucleotide-binding protein (G
      protein)-coupled receptors contains important regulatory sequences such as an
      NP(x)2-3Y motif, a site of fatty acid acylation, and serine- and threonine-rich
      domains. The type A CCK receptor contains all of these, yet their significance
      has not been examined. We have, therefore, constructed a series of receptor site
      mutants and truncations that interfere with each of these motifs and expressed
      each in Chinese hamster ovary cells where they were studied for radioligand
      binding, cell signaling, receptor internalization, and intracellular trafficking.
      Each construct was synthesized and transported appropriately to the cell surface,
      where CCK bound with high affinity, elicited an inositol 1,4, 5-trisphosphate
      response, and resulted in internalization and normal trafficking. Thus
      modification or elimination of each of these established sequence motifs had no
      substantial effect on any of these parameters of receptor and cellular function.
      However, an additional construct that truncated the carboxy terminus, eliminating
      an additional 15-amino-acid segment devoid of any currently recognized sequence
      motifs, resulted in a marked change in receptor trafficking, with all other
      parameters of receptor function normal. This mutant receptor construct was
      delayed at the stage of early endosomes, delaying its progress to the lysosome
      enriched perinuclear compartment from the rapid time course followed by wild-type
      receptor and all of the other constructs. It is proposed that this region of the
      CCK receptor tail contains a new motif important for intracellular receptor
      trafficking.

PMID- 9655685
TI  - Mucosal mast cells are involved in CCK disruption of MMC in the rat intestine.
AB  - Our aim was to determine if mucosal mast cells could be activated by endogenous
      CCK and, as a consequence, mediate CCK actions in the small intestine. Rats were
      prepared for electromyography to record electrical activity in the small
      intestine. In another group of animals, the duodenum was perfused to measure rat
      mast cell protease II (RMCP II) as indicative of mast cell degranulation.
      Endogenous CCK release was induced by administration of soybean trypsin inhibitor
      (SBTI) in conscious rats or by intraduodenal perfusion of ovalbumin hydrolysate
      (OVH) in anesthetized rats. CCK concentration was measured by bioassay on
      pancreatic acini. SBTI in control rats disrupted migrating motor complexes (MMC)
      for >40 min. In rats treated with the mast cell stabilizer ketotifen, SBTI did
      not induce any change in the MMC pattern. RMCP II concentration in the duodenal
      perfusate significantly increased after OVH. Perfusate from ketotifen-treated
      animals did not show any significant increase in RMCP II values during OVH
      perfusion, although CCK plasma concentration was not different from the control
      group. Furthermore, infusion of the CCK-B receptor antagonist L-365,260
      significantly blocked the increase of RMCP II concentration after OVH. Our
      results indicate that mucosal mast cells are degranulated by endogenous CCK
      release through stimulation of CCK-B receptors. Therefore mucosal mast cells
      participate in CCK intestinal actions.

PMID- 9655686
TI  - Substance P receptor expression in intestinal epithelium in clostridium difficile
      toxin A enteritis in rats.
AB  - We previously reported that the inflammatory effects of Clostridium difficile
      toxin A on rat intestine can be significantly inhibited with a specific
      neurokinin-1 receptor (NK-1R) antagonist. In this study we investigated the
      localization and expression of NK-1R mRNA and protein in rat intestine by in situ
      hybridization, Northern blot analysis, and immunohistochemistry, respectively,
      after exposure to toxin A. Northern blot analysis showed increased mucosal levels
      of NK-1R mRNA starting 30 min after toxin A administration. In situ hybridization
      showed that toxin A increased NK-1R mRNA expression in intestinal epithelial
      cells after 30, 120, and 180 min. In rats pretreated with the NK-1R antagonist CP
      96345 the increase in NK-1R mRNA levels after exposure to toxin A was inhibited,
      indicating that NK-1R upregulation is substance P (SP) dependent. One hour after
      exposure to toxin A many of the intestinal epithelial cells showed staining for
      NK-1R compared with controls. Specific 125I-SP binding to purified epithelial
      cell membranes obtained from ileum exposed to toxin A for 15 min was increased
      twofold over control and persisted for 4 h. This report provides evidence that NK
      1R expression is increased in the intestinal epithelium shortly after exposure to
      toxin A and may be important in toxin A-induced inflammation.

PMID- 9655687
TI  - Histamine stimulates ion transport by dog pancreatic duct epithelial cells
      through H1 receptors.
AB  - Histamine affects pancreatic secretion, but its direct action on ion transport by
      pancreatic duct epithelial cells (PDEC) has not been defined. We now characterize
      the secretory effects of histamine on cultured, well-differentiated, and
      nontransformed dog PDEC. Histamine stimulated, in a concentration-dependent
      manner (1-100 microM), a cellular 125I- efflux that was inhibited by 500 microM 5
      nitro-2-(3-phenylpropylamino)benzoic acid, 2.5 mM diphenylamine-2-carboxylate,
      and 500 microM DIDS and thus mediated through Ca2+-activated Cl- channels.
      Histamine-stimulated 125I- efflux was 1) inhibited by 100 microM diphenhydramine,
      an H1 receptor antagonist, 2) resistant to 1 mM cimetidine, an H2 receptor
      antagonist, 3) not reproduced by 1 mM dimaprit, an H2 agonist, and 4) inhibited
      by 50 microM 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-AM, a Ca2+
      chelator, suggesting that it was mediated through H1 receptors acting via
      increased cytosolic Ca2+. Histamine also stimulated a 86Rb+ efflux that was
      sensitive to 100 nM charybdotoxin and thus mediated through Ca2+-activated K+
      channels. When PDEC monolayers were studied in Ussing chambers, a short-circuit
      current of 21.7 +/- 3.1 microA/cm2 was stimulated by 100 microM histamine. This
      effect was inhibited by diphenhydramine but not cimetidine, was not reproduced
      with dimaprit, and was observed only after serosal addition of histamine,
      suggesting that it was mediated by basolateral H1 receptors on PDEC. In
      conclusion, histamine, acting through basolateral H1 receptors, activates both
      Ca2+-activated Cl- and K+ channels; in this manner, it may regulate PDEC
      secretion in normal or inflamed pancreas.

PMID- 9655688
TI  - Short-chain fatty acids inhibit intestinal trefoil factor gene expression in
      colon cancer cells.
AB  - Intestinal trefoil factor (ITF) gene expression was detected in five colon cancer
      cell lines. ITF was synthesized by mucous cells of LIM 1215 and LIM 1863 lines,
      from which it is secreted constitutively. The ITF mRNA transcript was estimated
      to be 0.6 kb. In LIM 1215 cells, the expression of ITF was potently and dose
      dependently inhibited by short-chain fatty acids (butyrate > propionate >
      acetate) within 8 h of application. The inhibitory effect of butyrate was ablated
      by actinomycin D and preceded its effects on differentiation of LIM 1215 cells as
      indicated by induction of alkaline phosphatase activity and counting of periodic
      acid-Schiff-positive cells. The human ITF promoter contained an 11-residue
      consensus sequence with high homology to the butyrate response element of the
      cyclin D1 gene. Mobility shift assays show specific binding of this response
      element to nuclear protein extracts of LIM 1215 cells. We conclude that butyrate
      inhibits ITF expression in colon cancer cells and that this effect may be
      mediated transcriptionally and independently of its effects on differentiation.

PMID- 9655689
TI  - Interaction between neurokinin A, VIP, prostanoids, and enteric nerves in
      regulation of duodenal function.
AB  - Neurokinin A (NKA) induces duodenal motility and increases mucosal permeability
      and bicarbonate secretion in the in situ perfused duodenum in anesthetized rats.
      In the present study, the NKA-induced increase in mucosal permeability was
      potentiated by luminal perfusion with lidocaine and diminished by vasoactive
      intestinal peptide (VIP) but unaltered by elevated intraluminal pressure.
      Elevation of intraluminal pressure, however, potentiated the stimulatory effect
      of NKA on bicarbonate secretion. In contrast, the tachykinin decreased the rate
      of alkalinization in rats subjected to elevated intraluminal pressure and treated
      with indomethacin. Similarly, NKA partially inhibited the VIP-stimulated
      bicarbonate secretion. Luminal lidocaine did not affect the secretory response to
      NKA. The motility induced by NKA was unaffected by VIP or lidocaine but decreased
      by elevated intraluminal pressure. It is concluded that the NKA-induced increase
      in duodenal mucosal bicarbonate secretion is independent of neurons and possibly
      mediated by prostanoids. The increase in mucosal permeability in response to NKA
      may be suppressed by mucosal nerves, perhaps utilizing VIP as one of the
      transmitters.

PMID- 9655690
TI  - Secretory effects of ATP on nontransformed dog pancreatic duct epithelial cells.
AB  - Extracellular triphosphate nucleotides, such as ATP, may regulate various
      cellular functions through specific cell surface receptors. We examine in this
      report the different secretory effects of ATP and analogs on nontransformed dog
      pancreatic duct epithelial cells (PDEC). We observed that 1) ATP, UTP, adenosine
      5'-O-(3-thiotriphosphate), and, to a lesser extent, beta, gamma-methylene-ATP,
      but not adenosine, stimulated 125I- efflux from PDEC, suggesting a primary role
      for P2Y2 receptors, 2) ATP-stimulated 125I- efflux was inhibited by 5-nitro-2-(3
      phenylpropylamino)benzoic acid, diphenylamine-2-carboxylate, and DIDS, suggesting
      mediation through Ca2+-activated Cl- channels, 3) ATP stimulated an 86Rb+ efflux
      sensitive to BaCl2 and charybdotoxin, thus likely occurring through Ca2+
      activated K+ channels, 4) serosal or luminal addition of UTP activated apical Cl-
      conductance and basolateral K+ conductance when nystatin-permeabilized PDEC were
      studied in an Ussing chamber, suggesting the expression of P2Y2 receptors on both
      sides of the cell, 5) ATP stimulated mucin secretion, and 6) ATP increases
      intracellular Ca2+ concentration ([Ca2+]i). In conclusion, ATP and UTP interact
      with P2Y2 receptors on nontransformed PDEC to increase [Ca2+]i, stimulate mucin
      secretion, and activate ion conductances; these findings have implications for
      pancreatic exocrine function in both health and disease, such as cystic fibrosis.

PMID- 9655691
TI  - Characterization of rat epimorphin/syntaxin 2 expression suggests a role in crypt
      villus morphogenesis.
AB  - The rodent intestinal mucosa undergoes a remarkable morphogenesis as the crypt
      villus axis is formed. Endoderm-mesenchymal interactions play a critical role in
      this process. Epimorphin is a mesenchymal protein postulated to play a role in
      lung and skin morphogenesis. The rat homologue, syntaxin 2, belongs to a family
      of integral membrane proteins that function in vesicle docking and fusion. To
      clarify its role in fetal gut morphogenesis, epimorphin expression was examined
      during ontogeny, in an isograft model of ischemic injury and mucosal repair, and
      during intestinal adaptation after small bowel resection. Epimorphin/syntaxin 2
      mRNA levels were increased in fetal gut during lumen formation and villus
      morphogenesis. mRNA levels remained elevated in the first 2 wk after birth and
      then declined at weaning. In situ hybridization showed epimorphin/syntaxin 2 mRNA
      in gestational day 14 (G14) and G15 intestinal mesenchymal cells and in the
      mucosal lamina propria during villus formation. Epimorphin/syntaxin 2 mRNA
      expression increased during villus repair in the isograft. In contrast, in the
      early stages of intestinal adaptation after small bowel resection,
      epimorphin/syntaxin 2 mRNA expression was suppressed in the adapting gut. We
      conclude the cell-specific and temporal patterns of epimorphin expression in the
      models used in this study suggest a role in the morphogenesis of the crypt-villus
      axis.

PMID- 9655692
TI  - S-adenosylmethionine deficiency and TNF-alpha in lipopolysaccharide-induced
      hepatic injury.
AB  - S-adenosylmethionine (Adomet) is a substrate for de novo synthesis of choline.
      Adomet deficiency occurs in certain types of liver injury, and the injury is
      attenuated by exogenous Adomet. Tumor necrosis factor-alpha (TNF-alpha) is also a
      mediator of these models of hepatotoxicity. We investigated the role of Adomet in
      lipopolysaccharide (LPS)-induced liver injury in rats made deficient in both
      Adomet and choline. Rats were maintained on either a methionine-restricted and
      choline-deficient (MCD) diet or a diet containing sufficient amounts of all
      nutrients [methionine and choline sufficient (MCS)] and then administered either
      LPS or saline. MCS-LPS rats had normal liver histology and no change in serum
      transaminases compared with the MCS-saline control group. MCD-saline rats had
      hepatosteatosis but no necrosis, and a five- to sevenfold increase in
      transaminases vs. the MCS-saline group. MCD-LPS rats additionally had
      hepatonecrosis and a 30- to 50-fold increase in transaminases. Exogenous Adomet
      administration to MCD-LPS rats corrected the hepatic deficiency of Adomet but not
      of choline, prevented necrosis but not steatosis, and attenuated transaminases.
      Serum TNF-alpha was sixfold higher in MCD rats even without LPS challenge and 300
      fold higher with LPS challenge. Exogenous Adomet attenuated increased serum TNF
      alpha in MCD-LPS rats.

PMID- 9655693
TI  - Kinetics of particle uptake in the domes of Peyer's patches.
AB  - Uptake of particulate antigenic matter, including microorganisms and vaccine
      bearing microspheres, by the intestinal mucosa takes place in the domes of the
      gut-associated lymphoid tissues and is achieved by membranous (M) cells, which
      continuously transport particles from the lumen to the underlying tissue where
      some particle components initiate immune reactions. Using yeast as tracer, we
      investigated the kinetics of particle uptake in the Peyer's patches of pigs. A
      suspension of baker's yeast (Saccharomyces cerevisiae) was injected into the gut
      lumen of anesthetized minipigs; the position of yeast cells in the tissue was
      determined after 1, 2.5, 4, and 24 h using fluorescence light- and thin-section
      electron microscopy. After 1 h, 18.5% of all M cells had taken up or were in
      close contact with yeast cells. The intercellular space of the epithelium
      contained a maximum of 60.8% of all yeast cells found in the tissue after 2.5 h,
      but only 1.3% had been phagocytosed by macrophages. After 4 h most yeast cells
      (77.8%) were found beneath the basal lamina, and most of these (89%) were found
      in macrophages. No yeast cells were detected in the Peyer's patch domes 24 h
      after application. The data show that transcytosis of yeast particles (3.4 +/-
      0.8 micron in diameter) by M cells takes <1 h. Without significant phagocytosis
      by intraepithelial macrophages, the particles migrate down to and across the
      basal lamina within 2.5-4 h, where they quickly get phagocytosed and transported
      out of the Peyer's patch domes.

PMID- 9655694
TI  - Origin of molecular species of diacylglycerol induced by bombesin in smooth
      muscle cells from rabbit rectosigmoid.
AB  - The source of early production of sn-1,2-diacylglycerol (DAG) has for a long time
      been exclusively linked to hydrolysis of phosphatidylinositol 4,5-diphosphate,
      which on receptor activation is hydrolyzed into DAG and inositol 1,4,5
      trisphosphate. We have investigated the origin of lipid sources of DAG production
      in smooth muscle cells, in response to contraction induced by peptide agonists.
      We have performed a quantitative analysis of the molecular species of DAG formed
      in relation to the known molecular composition of parent phospholipids. The
      molecular species of phospholipids are sufficiently unique that the phospholipid
      origin of DAGs and its quantitative contribution to their formation can be
      measured by HPLC. Cell suspensions (10-15 x 10(6) cells/ml) from the circular
      muscle of rabbit rectosigmoid were incubated in the presence of the contractile
      peptide agonist bombesin (BB) at 10(-6) M. Reactions were stopped at different
      time intervals from 30 s to 4 min. DAGs were extracted, purified by TLC, and
      benzoylated with benzoic anhydride. The benzoylated DAGs were first purified by
      TLC and then by normal phase HPLC before they were injected onto a reverse-phase
      column and eluted isocratically. Furthermore, phospholipids in the lipid extract
      [phosphatidylinositol (PI), phosphatidylcholine (PC), phosphatidylserine (PS),
      and phosphatidylethanolamine (PE)] were purified by TLC and similarly analyzed
      after hydrolysis to DAGs with phospholipase C (PLC). The DAG molecular species
      profiles for PI, PC, PS, and PE were all unique. Contraction of cells with BB
      gave noticeable increases (17-55%) in newly formed DAGs. The major phospholipid
      source of the newly formed DAGs at 30 s was only approximately 30% from PI, and
      the remainder was from PC. In contrast, after 4 min of BB stimulation, a decrease
      was seen in newly formed DAGs in the peak specific for PI hydrolysis. The data
      suggest that BB-induced contraction by activation of PLCs results in hydrolysis
      of different phospholipids. The DAGs formed as a result are qualitatively and
      quantitatively distinct. This could be the basis for the kinetically different
      pattern of sustained contraction observed with BB.

PMID- 9655695
TI  - IGF-I stimulates intestinal muscle cell growth by activating distinct PI 3-kinase
      and MAP kinase pathways.
AB  - Insulin-like growth factor I (IGF-I), acting via its cognate receptor, plays an
      autocrine role in the regulation of growth of intestinal muscle cells. In the
      present study the signaling pathways mediating the growth effects of IGF-I were
      characterized in cultured human intestinal smooth muscle cells. Growth induced by
      a maximally effective concentration of IGF-I (100 nM), measured as [3H]thymidine
      incorporation, was only partially inhibited by LY-294002 [phosphatidylinositol 3
      kinase (PI 3-kinase) inhibitor] or PD-98059 [mitogen-activated protein (MAP)
      kinase kinase (MEK) inhibitor] (86 +/- 7% and 35 +/- 6% inhibition, respectively)
      alone but was abolished by the two combined (114 +/- 18% inhibition), implying
      the participation of both pathways. IGF-I elicited time- and concentration
      dependent increases in PI 3-kinase activity. This effect was inhibited only by LY
      294002 (89 +/- 12%). IGF-I elicited time- and concentration-dependent
      phosphorylation of p44/p42 MAP kinase and increased MAP kinase activity. These
      effects were inhibited only by PD-98059 (78 +/- 9% and 98 +/- 7%, respectively).
      We conclude that in human intestinal muscle cells IGF-I activates distinct PI 3
      kinase and MAP kinase signaling pathways, which act in conjunction to mediate
      growth.

PMID- 9655696
TI  - Involvement of intracellular Ca2+ stores in inhibitory effects of NO donor SIN-1
      and cGMP.
AB  - We investigated the role of K+ channels and intracellular Ca2+ stores in the
      relaxations induced by the NO donor 3-morpholinosydnonimine (SIN-1) and 8-bromo
      cGMP (8-BrcGMP), 8-(4-chlorophenylthio)-cGMP (pCPT-cGMP), and alpha, beta
      methylene-ATP in isolated segments of rat ileum. The inhibitory responses to SIN
      1 and the cGMP analogs were not influenced by the K+ blockers apamin,
      charybdotoxin, iberiotoxin, or glibenclamide, whereas relaxations induced by
      alpha,beta-methylene-ATP were abolished by apamin and tetraethylammonium. The NO
      donor SIN-1 and the cGMP analogs were able to inhibit contractions induced by
      activation of L-type Ca2+ channels (BAY-K-8644), by carbachol (CCh), and by
      cyclopiazonic acid (CPA), a blocker of sarcoplasmic Ca2+-ATPase. However, the
      inhibition of the combined CPA and CCh response was reduced and the dose-response
      curve of SIN-1 shifted to the right. Intracellular Ca2+ stores were emptied by
      incubation in Ca2+-free buffer and repetitive stimulation with CCh or BAY-K-8644.
      After restoration of extracellular Ca2+, the inhibitory effect of SIN-1 and pCPT
      cGMP was only attenuated, whereas in the additional presence of CPA, the
      inhibitory effect of SIN-1 was blocked and the effect of 8-BrcGMP reduced. Thus
      depleting intracellular Ca2+ stores attenuated the effect of SIN-1 and 8-BrcGMP,
      suggesting an involvement of functional Ca2+ stores.

PMID- 9655697
TI  - Gastric emptying flow curves separated from carbon-labeled octanoic acid breath
      test results.
AB  - Recently, we developed the [13/14C]octanoic acid breath test to measure gastric
      emptying of solids. Although the method has been validated extensively,
      absorption, metabolism, and excretion of the label in the breath need to be
      corrected for. In this study a mathematical model was developed that allows for
      1) separation of the global CO2 excretion after ingestion of the labeled test
      meal into the emptying rate of the labeled test meal from mouth to pylorus and
      the postgastric processing of absorption, metabolism, and excretion of the label,
      and 2) numerical calculation of the half-emptying time and lag phase of the
      emptied meal. The model was applied to the gastric emptying results obtained by
      simultaneous scintigraphic and breath test measurements. An excellent correlation
      was found between the gastric half-emptying time (r = 0.98) and lag phase (r =
      0.85) determined scintigraphically and via breath test. There was also a good
      agreement between the two methods [mean values and confidence limits for
      differences: t1/2 = 10 min (-20 to 41) and tlag = -3 min (-39 to 34)]. Moreover,
      the separated gastric emptying curves, lacking the influence of postgastric
      processing of the label, showed real patterns of gastric outflow, which changes
      from moment to moment.

PMID- 9655698
TI  - Respiratory system mechanics in adult respiratory distress syndrome. Stretching
      our understanding.

PMID- 9655699
TI  - Acute respiratory distress syndrome caused by pulmonary and extrapulmonary
      disease. Different syndromes?
AB  - To assess the possible differences in respiratory mechanics between the acute
      respiratory distress syndrome (ARDS) originating from pulmonary disease (ARDSp)
      and that originating from extrapulmonary disease (ARDSexp) we measured the total
      respiratory system (Est,rs), chest wall (Est,w) and lung (Est,L) elastance, the
      intra-abdominal pressure (IAP), and the end-expiratory lung volume (EELV) at 0,
      5, 10, and 15 cm H2O positive end-expiratory pressure (PEEP) in 12 patients with
      ARDSp and nine with ARDSexp. At zero end-expiratory pressure (ZEEP), Est,rs and
      EELV were similar in both groups of patients. The Est,L, however, was markedly
      higher in the ARDSp group than in the ARDSexp group (20.2 +/- 5.4 versus 13.8 +/-
      5.0 cm H2O/L, p < 0.05), whereas Est,w was abnormally increased in the ARDSexp
      group (12.1 +/- 3.8 versus 5.2 +/- 1.9 cm H2O/L, p < 0.05). The IAP was higher in
      ARDSexp than in ARDSp (22.2 +/- 6.0 versus 8.5 +/- 2.9 cm H2O, p < 0.01), and it
      significantly correlated with Est,w (p < 0. 01). Increasing PEEP to 15 cm H2O
      caused an increase of Est,rs in ARDSp (from 25.4 +/- 6.2 to 31.2 +/- 11.3 cm
      H2O/L, p < 0.01) and a decrease in ARDSexp (from 25.9 +/- 5.4 to 21.4 +/- 55.5 cm
      H2O/L, p < 0.01). The estimated recruitment at 15 cm H2O PEEP was -0.031 +/-
      0.092 versus 0.293 +/- 0.241 L in ARDSp and ARDSexp, respectively (p < 0.01). The
      different respiratory mechanics and response to PEEP observed are consistent with
      a prevalence of consolidation in ARDSp as opposed to prevalent edema and alveolar
      collapse in ARDSexp.

PMID- 9655700
TI  - Lavage administration of dilute surfactants after acute lung injury in neonatal
      piglets.
AB  - Exogenous surfactant therapy is not standard in the acute respiratory distress
      syndrome (ARDS) because of a lack of proven benefit. Nonuniform surfactant
      distribution after either bolus or aerosol administration may be an important
      factor limiting response. In a previous study of acute lung injury, we
      demonstrated that lavage administration of Exosurf (13.5 mg phospholipid/ml) was
      both effective and distributed uniformly in the lungs. Since the endogenous
      surfactant pool is much smaller than the typical dose of exogenous surfactant
      administered, we hypothesized that dilute surfactant preparations (4-4.5 mg
      phospholipid/ml) administered by lung lavage would be equally effective in
      reversing pulmonary dysfunction in a piglet model of acute lung injury. We
      compared three dilute surfactants: Infasurf (n = 5), KL4-Surfactant (n = 6), and
      Exosurf (n = 5) with controls (n = 6) and undiluted Exosurf (13. 5 mg
      phospholipid/ml; n = 6). All dilute surfactant preparations were effective in
      improving oxygenation and other parameters of pulmonary function. Surfactant
      administered by lavage resulted in uniform lung distribution. We conclude that
      dilute surfactants administered by lung lavage are effective in reversing
      pulmonary dysfunction after acute lung injury. We speculate that doses in the
      range of 20-40 mg phospholipid/kg may be adequate to improve lung function in
      ARDS when exogenously administered surfactant is uniformly distributed in the
      lung.

PMID- 9655701
TI  - Automobile accidents in patients with sleep apnea syndrome. An epidemiological
      and mechanistic study.
AB  - To investigate the association between sleep apnea syndrome (SAS) and automobile
      accidents, and to evaluate potential underlying mechanisms, we prospectively
      recruited 60 consecutive patients with SAS (apnea-hypopnea index, 58 +/- 3 h-1)
      and 60 healthy control subjects, matched for sex and age. The number of
      automobile accidents during the past 3 yr was obtained from participants and
      insurance companies. We quantified the degree of daytime sleepiness (Epworth
      scale), anxiety and depression (Beck tests), and we assessed the level of
      vigilance (PVT 192) and driving performance (Steer-Clear). Patients had more
      accidents than control subjects (OR: 2.3; 95% CI: 0.97 to 5.33) and were more
      likely to have had more than one accident (OR: 5.2; 95% CI: 1.07 to 25.29, p <
      0.05). These differences persisted after stratification for km/yr, age, and
      alcohol consumption. Patients were more somnolent, anxious, and depressed than
      control subjects (p < 0.01), and they had a lower level of vigilance and poorer
      driving performance (p < 0.01). Yet, we did not find any correlation between the
      degree of daytime sleepiness, anxiety, depression, the number of respiratory
      events, nocturnal hypoxemia, level of vigilance, or driving simulator performance
      and the risk of automobile accidents among SAS patients. In conclusion, patients
      with SAS have an increased risk of automobile accidents. None of the clinical or
      physiological markers commonly used to define disease severity appear able to
      discriminate those patients at higher risk of having an automobile accident.

PMID- 9655702
TI  - The rise and dwell time for peak expiratory flow in patients with and without
      airflow limitation.
AB  - The response of peak expiratory flow (PEF) meters may be affected by the
      magnitude of PEF, the time taken to get to PEF, and the duration that the peak is
      sustained. We undertook a retrospective study to define the 10 to 90% rise time
      (RT) and dwell time for flow above 90% (DT90) and 95% (DT95) of PEF. Blows were
      analyzed that had been recorded using a pneumotachograph from 912 patients older
      than 17 yr of age (556 men) who routinely attended a lung function laboratory.
      For each subject, that blow with the largest PEF was used to derive the PEF,
      FEV1, FVC, RT, DT90, and DT95. The values for RT, DT90, and DT95 were negatively
      skewed with the median values for men of 58, 29, and 19 ms, respectively, being
      significantly shorter than those for the women of 67, 49, and 31 ms. From the 912
      subjects, there were 277 (153 men) who had all their spirometric indices within
      the normal range, and 305 (220 men) had both PEF and FEV1 more than 1. 645 SD
      below predicted, indicating airflow limitation. For subjects with airflow
      limitation the median RT was significantly smaller than in the normal subjects
      (men: 46 versus 72 ms, women: 50 versus 72 ms), and the same was found for DT90
      (men: 22 versus 40 ms, women: 27 versus 56 ms) and DT95 (men: 15 versus 26 ms,
      women: 18 versus 34 ms). We conclude that the dwell times for PEF are shorter in
      men, and the rise and dwell times are shorter in patients with airflow
      limitation. Profiles used to test PEF meters should encompass the range of rise
      and dwell times found in subjects most likely to be using PEF meters, that is,
      those with airflow limitation.

PMID- 9655703
TI  - Additivity of protein and nonprotein inhibitors of lung surfactant activity.
AB  - This study examined the degree of additivity of several physiologically relevant
      protein and nonprotein inhibitors in impairing the surface activity of whole and
      extracted calf lung surfactant (LS and CLSE) on a pulsating bubble apparatus at
      37 degrees C. Inhibitors investigated were albumin, hemoglobin, C16:0 and C18:1
      lysophosphatidylcholine (LPC), oleic acid (OA), palmitoleic acid (PA),
      arachidonic acid (AA), and mixed red blood cell membrane lipids (RBCML). In the
      absence of inhibitors, LS (0.5 mg/ml) and CLSE (0.75 mg/ml) reached minimum
      surface tensions < 1 mN/m within 5 min of bubble pulsation (20 cycles/min, 50%
      area compression). Each inhibitor acting alone was able to reduce the surface
      activity of LS and CLSE, either raising minimum surface tension or increasing the
      time course of surface tension lowering or both. Several combinations of
      inhibitors exhibited additivity in impairing LS or CLSE activity at a lower
      concentration in mixtures than when present alone (albumin plus either C16:0 LPC,
      C18:1 LPC, or RBCML; hemoglobin plus either C16:0 LPC, C18:1 LPC, RBCML, PA, OA,
      or AA). The degree of additivity, however, was typically small in terms of the
      magnitude of reduction in inhibitor concentration or the rise in minimum surface
      tension relative to the effects of the most severe single inhibitor present.
      Substantial synergy was not found for any of the combinations of protein and
      nonprotein inhibitors investigated. Mixtures of albumin with PA or AA actually
      had a reduced inhibitory effect on LS and CLSE activity compared with the free
      fatty acids alone, apparently because of albumin binding of these molecules. In
      all cases, the detrimental effects of mixed inhibitors on LS and CLSE activity
      were reversed at increased surfactant concentration. These results indicate that
      surfactant dysfunction in acute respiratory distress syndrome (ARDS) could be
      increased in severity by interactions between some inhibitory substances, but
      that supplementation with exogenous CLSE would be effective in reversing
      inactivation by the mixtures of blood proteins, membrane lipids, and fatty acids
      studied.

PMID- 9655704
TI  - Epidemiological association of airway inflammation with asthma symptoms and
      airway hyperresponsiveness in childhood.
AB  - The role of airway inflammation in childhood asthma is not well defined, despite
      modern treatment approaches recommending potent anti-inflammatory therapy for an
      increasing number of children. In this study, induced sputum analysis was used to
      investigate the relationships among sputum inflammatory cells (eosinophils and
      mast cells), asthma symptoms, and airway hyperresponsiveness to hypertonic saline
      in a cohort of 170 children aged 8-14 years. Children who reported asthma
      symptoms in the past 2 wk had a 2. 25-fold (95% to CI, 1.20-4.24) increased odds
      of having significant sputum eosinophilia. Hyperresponsiveness to hypertonic
      saline was strongly associated with higher levels of sputum eosinophils ([OR] 4.
      36, 1.70-11.20), sputum mast cells (OR 7.46, 2.48-22.75), and nasal eosinophils
      (OR 4.73, 1.89-11.86). Interestingly, boys were more likely than girls to have
      features of airway inflammation (sputum mast cells, OR 3.33, 1.15-9.65; nasal
      eosinophils, OR 3.25, 1.72-5. 97), which is consistent with the known increase in
      asthma prevalence in boys in this age group. Airway inflammation with eosinophils
      and mast cells is likely to be important in the pathogenesis of asthma in
      childhood. Induced sputum analysis can be used to evaluate this problem and has
      the potential to be a useful tool for monitoring therapy.

PMID- 9655705
TI  - Involvement of tachykinin NK3 receptors in citric acid-induced cough and
      bronchial responses in guinea pigs.
AB  - Aerosolized citric acid induces several pulmonary effects including
      bronchoconstriction, airway inflammation, and cough. Evidence from the use of
      tachykinin NK1 and NK2 receptor antagonists, as well as chronic treatment with
      high doses of capsaicin, have suggested that these effects are mediated through
      the release of tachykinins from sensory nerve endings. In the present study, we
      have investigated the effects of a tachykinin NK3 receptor antagonist, SR 142801
      (osanetant), on cough, bronchoconstriction, and bronchial hyperresponsiveness
      induced by aerosolized citric acid (0.4 M) in guinea pigs. SR 142801, at 0.3 and
      1 mg . kg-1 by intraperitoneal route, significantly inhibited cough in conscious
      guinea pigs by 57 +/- 3 and 62 +/- 10% (n = 8), respectively. In anaesthetized
      guinea pigs, it failed to inhibit the bronchoconstriction induced by citric acid
      when given alone but abolished it when combined with the tachykinin NK2 receptor
      antagonist, SR 48968 (saredutant). In guinea pigs pretreated with thiorphan (1 mg
      . kg-1), aerosolized citric acid (0.4 M, 1 h) induced airway hyperresponsiveness
      24 h later, displayed by an exaggerated response to the bronchoconstrictor effect
      of acetylcholine. A microvascular leakage hypersensitivity also occurred and was
      demonstrated by a potentiation of the plasma protein extravasation from bronchial
      vessels induced by histamine. When given once intraperitoneally at 1 mg . kg-1 30
      min before the citric acid exposure, SR 142801 inhibited both hyperresponsiveness
      to acetylcholine and the potentiation of histamine-induced increase in
      microvascular permeability. The results suggest that tachykinin NK3 receptors are
      involved in citric acid-induced effects on airways.

PMID- 9655706
TI  - Survival and FEV1 decline in individuals with severe deficiency of alpha1
      antitrypsin. The Alpha-1-Antitrypsin Deficiency Registry Study Group.
AB  - Subjects >= 18 yr of age with serum alpha1-antitrypsin (alpha1-AT) levels <= 11
      microM or a ZZ genotype were followed for 3.5 to 7 yr with spirometry
      measurements every 6 to 12 mo as part of a National Heart, Lung, and Blood
      Institute Registry of Patients with Severe Deficiency of Alpha-1-Antitrypsin.
      Among all 1,129 enrollees, 5-yr mortality was 19% (95% CI: 16 to 21%). In
      multivariate analyses of 1, 048 subjects who had been contacted >= 6 mo after
      enrolling, age and baseline FEV1% predicted were significant predictors of
      mortality. Results also showed that those subjects receiving augmentation therapy
      had decreased mortality (risk ratio [RR] = 0.64, 95% CI: 0. 43 to 0.94, p = 0.02)
      as compared with those not receiving therapy. Among 927 subjects with two or more
      FEV1 measurements >= 1 yr apart, the mean FEV1 decline was 54 ml/yr, with more
      rapid decline in males, those aged 30 to 44 yr, current smokers, those with FEV1
      35 to 79% predicted, and those who ever had a bronchodilator response. Among all
      subjects, FEV1 decline was not different between augmentation-therapy groups (p =
      0.40). However, among subjects with a mean FEV1 35 to 49% predicted, FEV1 decline
      was significantly slower for subjects receiving than for those not receiving
      augmentation therapy (mean difference = 27 ml/yr, 95% CI: 3 to 51 ml/yr; p =
      0.03). Because this was not a randomized trial, we cannot exclude the possibility
      that these differences may have been due to other factors for which we could not
      control.

PMID- 9655707
TI  - Cotinine excretion as a predictor of peak flow variability.
AB  - Environmental tobacco smoke (ETS) is suspected to be an important risk factor for
      bronchial hyperresponsiveness. In order to test the effect of ETS, we measured
      expiratory flow rates and urine cotinine excretion (UCE) within a narrow time
      window in two consecutive years. Maternal smoking habits and medical history were
      ascertained by standardized questionnaires. The percentage ratio of the amplitude
      over the mean (AVAM) of the diurnal peak flow rates of children (complete values
      from at least five consecutive days) was calculated as an indicator of bronchial
      responsiveness. The association of UCE and log10AVAM was analyzed by multiple
      linear regression. Complete data were available for a sample of 417 children. The
      median of UCE in children of parents who smoked (3.2 ng/mg and 2.9 ng/mg
      creatinine, Surveys 1 and 2, respectively) was higher than the median in children
      of nonsmoking parents (0 ng/mg in both surveys). With increasing UCE the
      log10AVAM rose in the first and second surveys, as well as in the longitudinal
      analysis (p = 0.003). This association, however, showed up only in boys (p =
      0.0001) and not in girls (p = 0.31). Our data suggest that there is a need both
      for further analysis of the gender difference and for more support of strategies
      against passive smoking as far as children are concerned, since airway
      hyperresponsiveness is a risk factor for chronic airway impairment.

PMID- 9655708
TI  - Evaluation of a new, rapid, and quantitative D-Dimer test in patients with
      suspected pulmonary embolism.
AB  - Previous studies have suggested the utility of D-Dimer ELISA assays in
      eliminating a diagnosis of pulmonary embolism (PE). Our objectives were to
      evaluate the performance of a new, rapid, quantitative, and automated Liatest D
      Dimer Assay in patients with suspected PE. Three hundred eighty-six consecutive
      patients referred to our institution between March 1992 and December 1996 for
      clinically suspected PE, with recent clinical signs not exceeding 1 wk, were
      included in this study. Diagnosis of PE was based on clinical evaluation,
      radionuclide lung imaging, lower limb examination, and, when required, pulmonary
      angiography. D-Dimer performances, for both Liatest D-Dimer and standard D-Dimer
      ELISA (Asserachrom DDi), assays, were assessed at the end of the study. Among the
      386 patients tested, 146 (37.8%) were classified as PE-positive. Liatest D-Dimer
      assay had a 100% sensitivity (95% confidence interval, 97 to 100%) and a negative
      predictive value of 100% (95% confidence interval, 94 to 100%). A normal result,
      below the cutoff of 500 ng/ml, occurred in 83 of the 386 (21%) patients. There
      was a strong agreement between Liatest D-Dimer and Asserachrom DDi analyses.
      These findings suggest that this rapid, quantitative, and automated D-Dimer assay
      provides a useful diagnostic tool for the clinician with regard to exclusion of
      PE.

PMID- 9655709
TI  - Lung volume reduction surgery has variable effects on blood gases in patients
      with emphysema.
AB  - Most studies of bilateral lung volume reduction surgery (LVRS) report increases
      in arterial oxygenation (PaO2). Some suggest this results from an increased
      alveolar ventilation, but others imply that ventilation-perfusion heterogeneity
      is reduced. We measured arterial blood gases (ABGs) on air before and 3 mo
      following LVRS in 46 patients (61% of eligible patients), estimate the difference
      between alveolar and arterial O2 (AaPO2), and correlated the changes observed
      with preoperative ABGs, and with pre-and postoperative pulmonary function. The
      mean +/- SD change in PaO2 and AaPO2 was +3 +/- 10 mm Hg (p = 0.058) and +1 +/-
      11 mm Hg (p = NS), respectively, and the range of change was large (-17 to +29 mm
      Hg and -24 to +23 mm Hg, respectively). The mean change in PaCO2 was -3 +/- 5 mm
      Hg (p < 0.05) and ranged from -11 to +5 mm Hg. Changes in PaO2 and AaPO2 were
      poorly correlated with changes in PaCO2 or with pre- or postoperative pulmonary
      function. Although some patients had a marked improvement in ABGs following LVRS,
      almost as many deteriorated. On average, only minimal effects were seen. Although
      mean alveolar ventilation improved somewhat, the effect of LVRS on PaO2 primarily
      resulted from alterations in ventilation-perfusion heterogeneity.

PMID- 9655710
TI  - Noninvasive monitoring of cardiac output in critically ill patients using
      transesophageal Doppler.
AB  - Measurement of cardiac output using thermodilution technique in mechanically
      ventilated patients is associated with significant morbidity. The goal of the
      present study was to assess the validity of cardiac output measurement using
      transesophageal Doppler in critically ill patients. Forty-six patients from three
      different intensive care units underwent 136 paired cardiac output measurements
      using thermodilution (COTH) and transesophageal Doppler (COTED). In addition,
      simultaneous suprasternal Doppler and indirect calorimetry (Fick principle) were
      used to measure cardiac output in 26 patients from one center. A good correlation
      was found between COTH and COTED (r = 0.95), with a small systematic
      underestimation (bias = 0.24 L/min) using transesophageal Doppler. The limits of
      agreement between COTH and COTED were +2 L/min and -1.5 L/min. Variations in
      cardiac output between two consecutive measures using either transesophageal
      Doppler or thermodilution techniques were similar in direction and magnitude
      (bias = 0 L/min; limits of agreement = +/-1.7 L/min). Suprasternal Doppler and
      indirect calorimetry yielded similar correlations and agreements in the subset of
      patients in whom they were used. These results confirm that transesophageal
      Doppler can provide a noninvasive, clinically useful estimate of cardiac output
      and detect hemodynamic changes in mechanically ventilated, critically ill
      patients.

PMID- 9655711
TI  - Endobronchial biopsy and bronchoalveolar lavage in stable lung transplant
      recipients and chronic rejection.
AB  - We have obtained endobronchial biopsies (EBB), bronchoalveolar lavage (BAL), and
      transbronchial biopsies (TBB) in 17 stable lung transplant recipients (sLTR), 8
      subjects with physiologic evidence of chronic rejection (BOS), and 9 normal
      subjects. A striking finding was the marked neutrophilia in BAL samples from
      patients with BOS, in the carefully screened absence of infection. A
      statistically higher neutrophil count was also present in the sLTR group relative
      to the normal group. Median BAL neutrophil count in BOS was 100 x 10(3)/ml, range
      13-1,661 10(3)/ml (p < 0.001 relative to normal subjects and sLTR). Median BAL
      neutrophil count in sLTR was 7 x 10(3)/ml, range 1-81 10(3)/ml (p < 0.01 relative
      to normal subjects). Normal subjects had a median BAL neutrophil count of 3 x
      10(3)/ml, range 1-7 10(3)/ml. There was evidence of a predominance of CD8
      lymphocytes in BAL from sLTR and BOS with a lower CD4/CD8 ratio in both compared
      to normal subjects (p < 0.05). EBB mononuclear cell counts, class II major
      histocompatibility complex expression, and T-cell activation markers were normal
      in BOS, in contrast to the sLTR group. Our data may be consistent with BOS,
      representing a relative resolution of an active mononuclear cell chronic
      inflammation, perhaps at the expense of airway fibrosis. The relevance of the BAL
      neutrophilia and its role in BOS pathogenesis need further longitudinal
      investigation.

PMID- 9655712
TI  - Differential effects of anti-cytokine treatment on bronchoalveolar hemostasis in
      endotoxemic chimpanzees.
AB  - Activation and inhibition of coagulation and fibrinolysis was analyzed in
      bronchoalveolar lavage (BAL) fluids obtained from endotoxin-challenged
      chimpanzees. The mediatory role of tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-6 (IL-6) on endotoxin-induced changes in bronchoalveolar coagulation
      and fibrinolysis was investigated in experiments in which the infusion of
      endotoxin was combined with the administration of monoclonal anti-TNF-alpha or
      anti-IL-6 antibodies. Endotoxin infusion elicited a marked increase in
      bronchoalveolar thrombin generation as measured by levels of prothrombin
      activation fragment F1+2 and thrombin-antithrombin complexes. Markers for
      intrinsic pathway activation were not detectable, suggesting that the thrombin
      generation was mediated by the tissue factor-dependent route. Levels of
      antithrombin were low before the injection of endotoxin and not detectable
      hereafter. The administration of anti-IL-6 antibody completely abolished the
      endotoxin-induced activation of bronchoalveolar coagulation, whereas treatment
      with anti-TNF-alpha antibody only partly inhibited this effect. Bronchoalveolar
      fibrinolytic activity, due to urokinase-type plasminogen activator (u-PA), was
      significantly depressed after endotoxin injection, mainly due to a striking
      increase in plasminogen activator inhibitor-2 levels in BAL fluid. The endotoxin
      induced effects on bronchoalveolar fibrinolysis could be blocked by the
      simultaneous administration of anti- TNF-alpha antibodies. We conclude that
      endotoxemia results in the activation of bronchoalveolar coagulation, which is
      apparently mediated by the tissue factor route of coagulation activation and
      which may be amplified by consumption of antithrombin III. Bronchoalveolar
      fibrinolytic activity is significantly abolished by increased levels of mainly
      PAI-2 after the injection of endotoxin. The endotoxin-induced effects on
      bronchoalveolar coagulation appears to be mediated by IL-6, whereas TNF-alpha
      seems to be the pivotal mediator of the endotoxin-induced depression of
      bronchoalveolar fibrinolysis.

PMID- 9655713
TI  - Allergen-induced early and late asthmatic responses are not affected by
      inhibition of endogenous nitric oxide.
AB  - Endogenous exhaled nitric oxide (NO) is increased during the late response to
      inhaled allergen in patients with asthma and may be bronchoprotective in asthma
      or have a deleterious effect when generated in excess under inflammatory
      conditions. To investigate this, we evaluated the effect of inhibiting endogenous
      NO production with nebulized NG-nitro-L-arginine methyl ester (L-NAME), a
      nonselective NO synthase (NOS) inhibitor, on early and late asthmatic responses
      to inhaled allergen in patients with mild allergic asthma. After a screening
      allergen challenge (AC), 22 male patients attended two visits conducted in a
      double-blind, randomized, placebo-controlled, crossover manner. Twelve patients
      demonstrating an early asthmatic response only (single responders) inhaled either
      L-NAME 170 mg or 0.9% saline 20 min before AC, with exhaled NO and FEV1 measured
      for 3 h. Ten patients demonstrating both early and late asthmatic responses (dual
      responders) were studied in a similar fashion but inhaled two further doses of L
      NAME or placebo 3.5 and 7 h after the initial dose, with exhaled NO and FEV1
      measured for 10 h. L-NAME reduced exhaled NO levels by 77 +/- 5% (p < 0.01) and
      71 +/- 7% (p < 0.01) in single and dual responders, respectively, but had no
      significant effect on early or late asthmatic responses. Following AC in single
      responders, the mean (+/- SEM) maximum fall in FEV1 after L-NAME and saline was
      21.2 +/- 2.9% and 23.8 +/- 3.0%, respectively, and in dual responders, 31.2 +/-
      4.5% and 31.8 +/- 5. 8% during the early asthmatic responses, and 27.4 +/- 3.9%
      and 30.6 +/- 4.5% during the late asthmatic responses, respectively. Area under
      the curve (AUC) did not significantly differ. AUC0-2 h in single responders after
      L-NAME and saline was 20.2 +/- 3.9 and 24.9 +/- 4.4 Delta% FEV1/h, and in dual
      responders, 37.6 +/- 8.4 and 36.7 +/- 8.4 Delta% FEV1/h, respectively, and 106.2
      +/- 18.9 and 117.1 +/- 22.4 Delta% FEV1/h, respectively, for the AUC4-10 h. This
      study suggests that in mild allergic asthma, endogenous NO neither protects
      against nor contributes to the processes underlying airway responses to inhaled
      allergen.

PMID- 9655714
TI  - Effects of spontaneous and hypercapnic hyperventilation on inspiratory effort
      sensation in normal subjects.
AB  - In order to elucidate if the inspiratory effort sensation (IES) associated with
      carbon dioxide (CO2) is independent of the concomitant increase in the
      ventilation, we studied 23 normal resting volunteers (mean age 34 +/- 11 yr)
      during CO2 rebreathing. Our main goal was to compare the IES at the same
      ventilation level under hypercapnic and isocapnic conditions. The protocol
      included: (1) basal measurements (BASAL); (2) hypercapnic ventilation (HV); (3)
      screen copy of ventilatory pattern during hypercapnia (COPY); (4) screen copy at
      basal end-tidal (partial) carbon dioxide pressure (PETCO2) (ISO); and (5)
      recovery (REC). During HV, PETCO2 increased to 54.8 +/- 0.78 mm Hg (p < 0.001)
      and ventilation (VE) from 12.0 +/- 0.50 to 28.1 +/- 1.19 L/min (p < 0.001). Borg
      value increased from 0.11 +/- 0.06 to 3.4 +/- 0.23 (p < 0.001). These values were
      not different during HV and COPY. During ISO, PETCO2 was 40.2 +/- 0. 59 mm Hg
      (not significant [NS] from BASAL), while VE remained unchanged: 29.9 +/- 1.29
      L/min (NS from HV and COPY). Interestingly, the Borg value during the ISO
      decreased to 1.86 +/- 0.28 (p < 0.001 compared with HV and COPY). The increased
      IES induced by hypercapnic ventilation was reduced at the same ventilation level
      during isocapnic conditions. We suggest that CO2 generates an IES independent of
      the concomitant increase in ventilation.

PMID- 9655715
TI  - Analysis of HLA-DPB1 polymorphisms in African-Americans with sarcoidosis.
AB  - Several studies have found weak associations between certain human leukocyte
      antigen (HLA) alleles and sarcoidosis, but none have been conclusive. Glutamic
      acid at position 69 in HLA-DPB1 has been reported to be strongly associated with
      chronic beryllium disease. The immunopathologic and clinical similarities between
      chronic beryllium disease (CBD) and sarcoidosis suggest that similar immune
      response genes may be involved in susceptibility in both diseases. We analyzed
      the DNA sequence of HLA-DPB1 exon 2, which contains the hypervariable regions
      involved in binding antigens, in blood samples from African-American sarcoidosis
      patients and healthy controls. Results indicate that Val36 (odds ratio [OR] =
      2.30) and Asp55 (OR = 2.03) are associated with increased risk for sarcoidosis,
      but no association with Glu69 was found. These results suggest that although HLA
      DPB1 Glu69 is not associated with sarcoidosis, other alleles may make some
      contribution to susceptibility to sarcoidosis in African-Americans.

PMID- 9655716
TI  - A placebo-controlled trial of a HEPA air cleaner in the treatment of cat allergy.
AB  - To evaluate the effect of a room high-efficiency particulate air (HEPA) cleaner
      on cat-induced asthma and rhinitis, 35 cat-allergic subjects who were living with
      one or more cats were studied in a double-blind, placebo controlled trial. After
      a 1 mo baseline period, subjects' bedrooms were equipped with an active or
      placebo air cleaner for the following 3 mo. Evaluations included monthly
      measurement of cat-allergen levels, daily morning, afternoon, and nighttime nasal
      and chest-symptom scores, twice-daily measurement of peak-flow rates, daily
      medication scores, monthly spirometry, and methacholine (MCh) challenge testing
      before and after the study. Airborne allergen levels were reduced in the active
      filter group as compared with the placebo group (p = 0.045). However, no
      differences were detected in settled-dust allergen levels (p = 0.485), morning,
      afternoon, or nighttime nasal-symptom scores (p = 0.769, 0.534, and 0.138), chest
      symptom scores (p = 0.388, 0.179, and 0.215), sleep disturbance (p = 0.101),
      morning or afternoon peak-flow rates (p = 0. 424 and 0.679), or rescue medication
      use (nasal, p = 0.164, chest, p = 0.650), respectively. Although the combination
      of a HEPA room air cleaner, mattress and pillow covers, and cat exclusion from
      the bedroom did reduce airborne cat-allergen levels, no effect on disease
      activity was detected for any parameter studied.

PMID- 9655717
TI  - Starting with a higher dose of inhaled corticosteroids in primary care asthma
      treatment.
AB  - New British guidelines on the treatment of asthma (9) advocate starting with a
      higher dose of inhaled corticosteroids in newly detected asthma patients. We
      investigated whether initiating inhaled steroid treatment with a higher dose is
      clinically more effective than a lower dose in steroid naive patients with
      asthma. The study had a 13-wk randomized, double-blind, parallel design: 1-mo
      treatment with 400 microg budesonide twice a day, or 100 microg budesonide twice
      a day by dry powder inhaler, and follow-up treatment period of 2 mo with 200
      microg budesonide once daily for all patients. Forty patients started with 400
      microg budesonide twice daily, 44 with 100 microg budesonide twice daily. Mean
      age was 32 yr, baseline FEV1 value 84% predicted, reversibility 9% from baseline,
      and mean bronchodilator use 1.6 inhalations/d in the run-in period. After 4 wk of
      treatment with 400 microg and 100 microg budesonide twice daily mean morning peak
      expiratory flow (PEF) increased 27 L/min (SD 50), and 38 L/ min (SD 53),
      respectively (p = 0.30); mean symptom score improved from 1.1 to 0.6 and from 1.1
      to 0.5. These effects were maintained in the 2 mo follow-up. This study suggests
      that starting inhaled corticosteroids at a higher dose is not superior to a lower
      dose in the treatment of newly detected asthma.

PMID- 9655718
TI  - Inhaled corticosteroids and the prevention of readmission to hospital for asthma.
AB  - Despite the proven efficacy of inhaled corticosteroids in reducing airway
      inflammation and their increasing use for the treatment of asthma since the mid
      1980s, hospitalization for asthma has been increasing in frequency in several
      countries. Only few studies, reporting contradictory results, have investigated
      the role of inhaled corticosteroids in the prevention of hospitalizations for
      asthma. Using a cohort of 2,059 hospitalized asthmatic patients between 5 and 54
      yr of age, we estimated the effectiveness of inhaled corticosteroids in
      preventing a readmission to hospital for asthma as a function of the duration of
      therapy. The cohort was selected from the databases of Saskatchewan Health from
      1977 to 1993. The rate ratio (RR) of a readmission for asthma varied with
      duration of regular therapy with inhaled corticosteroids. During the first 15 d
      of regular therapy, users of inhaled corticosteroids were as likely as nonusers
      of these medications to be readmitted for asthma with a RR of 1.2 (95% CI: 0.8
      1.8). Subjects treated regularly with inhaled corticosteroids for at least 16 d
      and as long as 6 mo were 40% less likely to be readmitted for asthma (RR = 0.6;
      95% CI: 0.4-0.9), while after 6 mo of regular treatment the protective effect
      disappeared (RR = 1.3; 95% CI: 0.7-2.4). We conclude that regular therapy with
      inhaled corticosteroids can substantially reduce the risk of a readmission for
      asthma after only 15 d of use. Confounding by severity appears as the most likely
      explanation for the disappearance of the beneficial effect after 6 mo of regular
      therapy.

PMID- 9655719
TI  - Capitation, managed care, and chronic obstructive pulmonary disease.
AB  - Expenditure and utilization patterns of aged Medicare beneficiaries with chronic
      obstructive respiratory disease (COPD) (n = 42,472) were compared with all
      Medicare beneficiaries (n = 1,221,615) using a 5% nationally representative
      sample of aged Medicare beneficiaries participating in the fee-for-service
      program in 1992. Per capita expenditures for an aged Medicare beneficiary with
      COPD were 2.4 times the per capita expenditures for all Medicare beneficiaries.
      The most expensive 10% of Medicare beneficiaries with COPD accounted for nearly
      half of total expenditures for this population. Higher comorbidity, as measured
      by the Deyo-adapted Charlson index, was associated with higher expenditures. For
      Medicare Part B claims, internal medicine accounted for the largest portion of
      physician expenditures (14%). Per capita expenditures for pulmonologists were 7.5
      times higher for beneficiaries with COPD compared with all Medicare
      beneficiaries. Results from this study suggest that there is a subgroup of
      individuals with COPD who are likely to be very expensive during the year.
      Additional analytic studies are needed to more specifically identify
      characteristics associated with these individuals. As more Medicare beneficiaries
      enroll in managed care and as physicians are increasingly being paid on a
      capitated basis this information will be useful to physicians as they monitor the
      care provided to patients and assess the financial risks they accept under
      capitation.

PMID- 9655720
TI  - Influence of pulmonary bacteriology and histology on the yield of diagnostic
      procedures in ventilator-acquired pneumonia.
AB  - We investigated the influence of pulmonary bacteriology and histology on the
      yield of diagnostic procedures in a clinically relevant model of ventilator
      acquired pneumonia (VAP). Twenty-seven piglets entered a 4-d protocol of
      ventilatory support under general anesthesia. Endotracheal aspirates (EA),
      protected specimen brush (PSB), and bronchoalveolar lavage (BAL) were obtained on
      Day 4. PSB and BAL were performed under bronchoscopic guidance in dependent and
      nondependent lung segments. Immediately thereafter sternotomy allowed bilateral
      lung biopsies including the segments studied by bronchoscopic techniques. All
      respiratory specimens were then processed for microscopic examination and
      quantitative cultures (QC). In this model where many of the confounding factors
      often present in human studies were absent, we found that (1) although the local
      bacterial burden tended to correlate with the presence and the severity of
      histologic lesions, no definite bacteriologic cutoff could differentiate the
      histologic presence or absence of pneumonia; (2) histologic lesions of pneumonia
      and parenchymal bacterial burden were unevenly distributed through the lungs; (3)
      this heterogeneity in bacterial distribution also held true for single bacterial
      species; (4) using discriminative values of >= 10(3) cfu/ml, >= 10(4) cfu/ml, and
      >= 10(5) cfu/ml to define positive PSB, BAL, and EA cultures, respectively, these
      techniques identified the histologic presence of pneumonia with a sensitivity of
      69%, 78%, and 100%, respectively; (5) the specificity of these techniques in
      recognizing VAP was less than 50%; (6) with these discriminative values, less
      than 50% of PSB and BAL specimens correctly identified the causative organisms,
      whereas 94% of EA specimens correctly established the microbiologic diagnosis of
      pneumonia. We believe that the peculiar histologic and bacteriologic features of
      VAP may account for the difficulties of PSB and BAL, which combine QC with the
      use of discriminative thresholds, to reliably recognize pneumonia and to identify
      the causative organisms. For clinical practice, no technique confidently helps in
      recognizing pneumonia in mechanically ventilated patients. With regard to
      bacterial diagnosis, use of quantitative cultures of EA seems to be the best
      technique to identify the causative organisms in patients suffering VAP.

PMID- 9655721
TI  - Effect of continuous positive airway pressure on forced expiratory flows in
      infants with tracheomalacia.
AB  - Continuous positive airway pressure (CPAP) is used to minimize airway collapse in
      infants with tracheomalacia. Forced expiratory flows (FEFs) at functional
      residual capacity (FRC) increase with increasing CPAP in infants with
      tracheomalacia, and it has been suggested that CPAP prevents airway collapse by
      "stenting" the airway open. Since FEF is greater at higher than at lower lung
      volumes, we evaluated whether the increase in flow measured at FRC (V FRC) with
      CPAP could be explained by the increase in FRC with CPAP. We measured full FEF
      volume curves at CPAP levels of 0, 4, and 8 cm H2O in six infants with
      tracheomalacia and five healthy control infants. In both groups of infants, FVC
      did not change with CPAP; however, inspiratory capacity (IC) decreased and thus
      FRC increased with increasing CPAP. FEFs at FRC increased with increasing levels
      of CPAP; however, the FEFs at 50% and 75% of expired volume were not different
      for the three levels of CPAP for both groups of infants. Our finding that FEFs
      measured at the same lung volumes did not differ for the different levels of CPAP
      indicates that CPAP affects forced flows primarily by increasing lung volume.

PMID- 9655722
TI  - Airway mucosal blood flow in bronchial asthma.
AB  - As an inflammatory airway disease, asthma is expected to be associated with an
      increase in airway blood flow. We therefore compared airway mucosal blood flow
      (Qaw) among normal subjects (n = 11) and patients with stable asthma receiving (n
      = 13) or not receiving (n = 10) long-term inhaled glucocorticosteroid (GS)
      therapy. Qaw was calculated from the uptake of dimethyl ether in the anatomic
      dead space minus the most proximal 50 ml (DS), and expressed as blood flow per ml
      DS. Mean (+/- SE) Qaw was 38.5 +/- 5. 3 microl . min-1 . ml-1 in normals, 68.2 +/
      7.9 microl . min-1 . ml-1 in GS-naive asthmatics (p < 0.01), and 55.4 +/- 5.3
      microl . min-1 . ml-1 in GS-treated asthmatics (p < 0.05). Ten minutes after
      administration of 180 microg albuterol by metered dose inhaler, mean Qaw
      increased by 83 +/- 26% in normal subjects (p < 0.01), but did not change
      significantly in GS-naive (+5 +/- 8%) or GS-treated (+32 +/- 15%) asthmatics.
      These results demonstrate that Qaw is increased in stable asthmatics and
      resistant to further increase by a standard inhaled dose of a beta-adrenergic
      agonist.

PMID- 9655723
TI  - Paradoxical worsening of tuberculosis following antiretroviral therapy in
      patients with AIDS.
AB  - Transient worsening of tuberculous symptomatology and lesions following
      antituberculous therapy (paradoxical response) has previously been described as a
      rare occurrence. To determine the incidence of paradoxical responses in patients
      with AIDS and TB who are treated with antituberculous therapy and subsequently
      with combination antiretroviral therapy (ARV), we conducted a prospective study
      of 33 HIV-seropositive TB patients treated with anti-TB therapy and
      antiretroviral therapy (Group 1) compared with 55 HIV-seronegative TB patients
      treated with anti-TB therapy (Group 2) and 28 HIV-seropositive TB patients
      treated with anti-TB therapy but not on antiretrovirals (historical control;
      Group 3). In Group 1 patients, paradoxical responses were temporally more related
      to the initiation of ARV than to the initiation of anti-TB therapy (mean +/- SD:
      15 +/- 11 d versus 109 +/- 72 d [p < 0.001]) and occurred much more frequently
      (12 of 33; 36%) compared with Group 2 (1 of 55; 2%) (p < 0.001) or with Group 3
      (2 of 28; 7%) (p = 0.013). The majority of patients who experienced paradoxical
      responses and received tuberculin purified protein derivative (PPD) in Group 1
      had their tuberculin skin tests convert from negative to strongly positive after
      ARV. These observations suggest that a paradoxical response associated with
      enhanced tuberculin skin reactivity may occur after the initiation of ARV in HIV
      infected TB patients. Furthermore, the skin test conversion after the initiation
      of ARV may have important public health implications.

PMID- 9655724
TI  - Differences in familial segregation of FEV1 between asthmatic and nonasthmatic
      families. Role of a maternal component.
AB  - Studies have demonstrated familial aggregation of lung function. This study
      employed segregation analysis to investigate the mode of inheritance of FEV1
      using regressive models for continuous traits. The study population comprised 309
      families (1,163 individuals) enrolled in the Tucson Children's Respiratory Study
      who had both parents and at least one child with FEV1 data. Results showed
      significant genetic heterogeneity among the 87 families (328 individuals) with at
      least one member with asthma and the 222 families (835 individuals) with no
      asthmatic members. In families with no asthmatic members, all statistical models
      were rejected, indicating the absence of a major gene controlling lung function.
      However, a significant familial component indicated a strong
      polygenic/multifactorial mode of inheritance. In families with asthmatic
      member(s), results suggested polygenic/multifactorial inheritance with weak
      evidence for a Mendelian component expressed in a recessive fashion. However,
      while both father-offspring and mother-offspring correlations were statistically
      significant in families with no asthmatic members, only the mother-offspring
      correlation was significant in families with asthmatic members. The data suggest
      that lung function is inherited as a polygenic/multifactorial trait, but in
      asthmatic families a major element of intergenerational correlation is associated
      with a maternal influence, which may be genetically or environmentally mediated.

PMID- 9655725
TI  - Environmental tobacco smoke and adult asthma. The impact of changing exposure
      status on health outcomes.
AB  - The effect of environmental tobacco smoke (ETS) exposure on adults with asthma
      has not been well characterized. In a prospective cohort study of 451 nonsmoking
      adults with asthma, we evaluated the impact of ETS exposure on asthma severity,
      health status, and health care utilization over 18 mo. There were 129 subjects
      (29%; 95% CI, 25-33%) who reported regular ETS exposure, falling into three
      categories: exposure at baseline but none at follow-up (n = 43, 10%), no baseline
      exposure and new exposure at follow-up (n = 56, 12%), and exposure at both
      baseline and follow-up (n = 30, 7%). In cross-sectional analyses, subjects with
      baseline ETS exposure had greater severity-of-asthma scores (score difference,
      1.7; 95% CI, 0. 2-3.1), worse asthma-specific quality of life scores (score
      difference, 3.5; 95% CI, 0.03-7.0), and worse scores on the Medical Outcomes
      Study SF-36 physical component summary (score difference, 3. 0; 95% CI, 0-6.0)
      than unexposed subjects. They also had greater odds of emergency department
      visits (odds ratio [OR] = 2.1; 95% CI, 1.2-3.5), urgent physician visits (OR =
      1.9; 95% CI, 1.1-3.3), and hospitalizations (OR = 1.9; 95% CI, 1.02-3.6). In
      longitudinal follow-up, subjects reporting ETS cessation showed improvement in
      severity-of-asthma scores (score reduction, -3.2; 95% CI, -4.4 to -2. 0) and
      physical component summary scores (score increase, 5.3; 95% CI, 2.6-8.1).
      Environmental tobacco smoke cessation decreased the odds of emergency department
      visits (OR = 0.4; 95% CI, 0.2-0.97) and hospitalizations (OR = 0.2; 95% CI, 0.04
      0.97) after adjustment for covariates. Environmental tobacco smoke initiation was
      associated with greater asthma severity only in subjects with high-level (>= 3
      h/wk) exposure (score increase, 1.4; 95% CI, 0.03-2.7). In conclusion, self
      reported ETS exposure is associated with greater asthma severity, worse health
      status, and increased health care utilization in adults with asthma.

PMID- 9655726
TI  - Parental history and the risk for childhood asthma. Does mother confer more risk
      than father?
AB  - Although heredity plays a major role in asthma and in other allergic diseases,
      mechanisms underlying the inheritance of these disorders are poorly understood,
      as is the relative contribution of maternal and paternal conditions to risk of
      disease. We investigated doctor-diagnosed maternal and paternal asthma, eczema,
      and hay fever as cross-sectional predictors of childhood asthma and allergic
      disease in 306 children with a median age of 3.5 yr from families in which at
      least one parent had a history of either asthma or other allergic conditions. For
      both childhood asthma and eczema, the strongest parental predictors were the same
      conditions in the parents. For asthma in particular, maternal asthma was most
      strongly associated with asthma in the child over all ages in both univariate (OR
      = 3.2, 95% CI = 1.5 to 6.7) and multivariable (OR = 4.1, 95% CI = 1.7 to 10.1)
      models. Paternal asthma was weakly associated with childhood asthma in the
      univariate model (OR = 1.4, 95% CI = 0.6 to 3.2), but this association increased
      in magnitude in the multivariable model (OR = 2.7, 95% CI = 1.0 to 7.2). Among
      the children < 5 yr of age, the risk for childhood asthma associated with
      maternal asthma (OR = 5.0, 95% CI = 1.7 to 14.9) was greater than the risk
      associated with paternal asthma (OR = 1.6, 95% CI = 0. 5 to 5.9), whereas both
      maternal asthma and paternal asthma were associated with similar risks among
      children >= 5 yr of age (OR = 4. 6, 95% CI = 1.1 to 19.0 and OR = 4.1, 95% CI =
      1.0 to 16.0, respectively). The odds of having a child with asthma were three
      times greater in families with one asthmatic parent and six times greater in
      families with two asthmatic parents than in families where only one parent had
      inhalant allergy without asthma; furthermore, inhalant allergy in one parent also
      conferred additional risk in the presence of asthma in the other parent. Further
      investigation is needed into the relative importance of genetic factors and in
      utero and postnatal exposures in determining the differential effects of maternal
      and paternal asthma on the development of childhood asthma.

PMID- 9655727
TI  - Molecular markers of acute upper airway inflammation in workers exposed to fuel
      oil ash.
AB  - Biomarkers in nasal lavage (NL) fluid may be useful in determining the presence
      and severity of upper airway inflammation. We studied 18 boilermakers overhauling
      a large, oil-fired boiler and 11 utility workers who served as controls for 6 wk.
      NL was performed before (NL1), during (NL2), and after (NL3) the overhaul. We
      measured nasal fluid levels of interleukins 6 (IL-6) and 8 (IL-8), eosinophilic
      cationic protein (ECP), and myeloperoxidase (MPO) as markers of response to fuel
      oil ash exposure. In boilermakers, MPO was elevated during boiler work versus
      preboiler work (mean = 33.8 versus 22.7 ng/ml, p < 0.05), and at the 2-wk
      postexposure lavage (NL3) it had declined to 24.2 ng/ml (p = 0.08). Mean IL-8
      levels increased in boilermakers between NL1 and NL2 (mean = 83.8 versus 134.8
      pg/ml, p < 0.05), then decreased at NL3 (mean = 134.8 versus 89.0 pg/ml, p <
      0.05). Nasal fluid vanadium increased in boilermakers between NL1 and NL2 (median
      < 1.0 versus 4.7 ppb, respectively, p < 0.05), then decreased at NL3 (median, 4.7
      versus < 1.0 ppb, respectively, p < 0. 05). Levels of IL-6 and ECP did not change
      significantly during the study. Utility workers showed no significant change in
      any marker during the study period. Particulate matter < 10 micro(m) (PM10)
      levels were higher for boilermakers than for utility workers before boiler work
      (geometric mean (GM) = 0.40 versus 0.10 mg/m3, p < 0.05). This difference was
      more significant during boiler work (GM = 0.47 versus 0.13 mg/m3, p < 0.001).
      Ozone levels were low during the study. These data suggest that exposure to fuel
      oil ash results in acute upper airway inflammation, potentially mediated by
      increased IL-8 levels and the recruitment and activation of polymorphonuclear
      leukocytes. These changes were associated with significantly increased PM10
      levels and concentrations of upper airway vanadium.

PMID- 9655728
TI  - Prognostic value of hypercapnia in patients with chronic respiratory failure
      during long-term oxygen therapy.
AB  - Hypercapnia observed in patients with chronic respiratory failure may not be an
      ominous sign for prognosis when they are receiving long-term oxygen therapy
      (LTOT). In this study, we selected 4,552 patients with chronic obstructive
      pulmonary disease (COPD) and 3,028 with sequelae of pulmonary tuberculosis (TBsq)
      receiving LTOT from 1985 to 1993 throughout Japan and prospectively analyzed
      their prognoses. The hypercapnic patients (PaCO2 >= 45 mm Hg) had a better
      prognosis than the normocapnic patients (35 <= PaCO2 < 45 mm Hg) for TBsq, but no
      difference was found between the two groups with COPD. Furthermore, Cox's
      proportional hazards model revealed that in TBsq hypercapnia was an independent
      factor for favorable prognosis, and that the relative risk for mortality was 0.76
      in patients with 45 <= PaCO2 < 55 mm Hg, 0.64 for those with 55 <= PaCO2 < 65 mm
      Hg, and 0. 49 for patients with PaCO2 >= 65 mm Hg against normocapnic patients.
      This favorable effect of hypercapnia in TBsq was particularly apparent in the
      patients without severe airway obstruction. Even a rise of 5 mm Hg or more in
      PaCO2 over the initial 6- to 18-mo follow-up period was not associated with poor
      prognosis in TBsq, although it was in COPD. From these findings, we conclude that
      hypercapnia should not be generally considered an ominous sign for prognosis in
      those patients who receive LTOT.

PMID- 9655729
TI  - The pressure-volume curve is greatly modified by recruitment. A mathematical
      model of ARDS lungs.
AB  - A mathematical model of the ARDS lung, with simulated gravitational superimposed
      pressure, evaluated the effect of varying alveolar threshold opening pressures
      (TOP), PEEP and peak inspiratory pressure (PIP) on the static pressure-volume
      (PV) curve. The lower inflection point (Pflex) was affected by SP and TOP, and
      did not accurately indicate PEEP required to prevent end-expiratory collapse.
      Reinflation of collapsed lung units (recruitment) continued on the linear portion
      of the PV curve, which had a slope at any volume greater than the total
      compliance of aerated alveoli. As recruitment diminished, the reduced PV slope
      could produce an upper Pflex at 20 to 30 cm H2O pressure. An upper Pflex caused
      by alveolar overdistension could be modified or eliminated by recruitment with
      high TOP. With constant PIP as PEEP increased, and TOP range of 5 to 60 cm H2O,
      PEEP to prevent end-expiratory collapse was indicated by minimum PV slope above
      20 cm H2O, minimum hysteresis, and maximum volume at a pressure of 20 cm H2O.
      With constant inflation volume as PEEP increased, the effect on PV slope was
      unpredictable. Although increased PV slope indicated recruitment, maximum PV
      slope usually underestimated PEEP required to prevent end-expiratory collapse.
      Therefore, with this model the PV curve did not reliably predict optimal
      ventilator settings.

PMID- 9655730
TI  - Airway hyperresponsiveness in asthma. Not just a problem of smooth muscle
      relaxation with inspiration.
AB  - Airway hyperresponsiveness in asthma has been attributed to impaired ability of
      deep inspiration (DI) to stretch airway smooth muscle. We have retested this
      hypothesis by comparing the responses to methacholine of 10 asthmatic and 10
      control subjects. After each dose subjects breathed tidally without deep
      inspiration for 4 min, followed by a forced partial expiration from which flow
      was measured at a constant volume, 35% baseline VC (Vp 35). This index is
      independent of both DI and increases in end-inspiratory lung volume (EILV). EILV
      increased significantly more in the asthmatic group than in the control group
      (15.0 versus 2.5% of baseline VC, p = 0. 019), a factor that if not taken into
      account would tend to mask the difference in the two responses. Comparisons were
      made after a cumulative dose of 50 microg methacholine, which was the highest
      dose common to all subjects. The asthmatic response was significantly greater
      than that seen in the control group, with reductions to 25.9 and 72.1% of
      baseline Vp 35, respectively (p = 0. 0007). We conclude that the sensitivity of
      asthmatic airways to methacholine is greater than that of normal airways even
      when DI is prohibited. Therefore, the hyperresponsiveness of asthmatic airways is
      not attributable simply to an inability of DI to stretch airway smooth muscle.

PMID- 9655731
TI  - Total sputum nitrate plus nitrite is raised during acute pulmonary infection in
      cystic fibrosis.
AB  - Nitric oxide (NO) can be detected in exhaled gas in human subjects. It is
      produced by nitric oxide synthase (NOS) and is rapidly metabolized to nitrite and
      nitrate (NO2/NO3). Exhaled NO is reported to be elevated in patients with asthma,
      bronchiectasis, or upper respiratory tract infection. Recent reports have shown
      no increase of exhaled NO in stable cystic fibrosis (CF). We hypothesized that
      NOS activity is increased in patients with acute pulmonary exacerbation of CF. We
      therefore measured exhaled NO and sputum NO2/NO3 in three subject categories:
      patients with acute pulmonary exacerbation of CF, patients with stable CF, and
      healthy control subjects. Mean +/- SD exhaled NO was significantly higher in
      control subjects (8.8 +/- 4.9 ppb) than in both acute (3.8 +/- 3.9 ppb) and
      stable (5.0 +/- 2.5 ppb) patients. Sputum NO2/NO3 was significantly higher in
      acute patients (774 +/- 307 micromol/L) when compared with both stable patients
      (387 +/- 203 micromol/L) and control (421 +/- 261 micromol/L) subjects. Sputum
      NO2/NO3 did not return to normal in a subgroup of patients assessed after 2 wk of
      intensive antibiotic and glucocorticoid treatment. These results confirm that
      exhaled NO is not a useful measure of airway inflammation in CF. Elevated levels
      of sputum NO2/NO3 suggest that NOS is activated during acute pulmonary
      exacerbations of CF.

PMID- 9655732
TI  - Addition of salmeterol versus doubling the dose of beclomethasone in children
      with asthma. The Dutch Asthma Study Group.
AB  - Studies in adults revealed that addition of salmeterol to a moderate dose of
      inhaled corticosteroid resulted in better symptom control and higher PEF compared
      with doubling the dose of inhaled corticosteroid. The aim of this three group
      study was to compare the effects of a moderate dose of beclomethasone, the same
      dose of beclomethasone with salmeterol, and a doubling dose of beclomethasone on
      lung function and symptoms in children with moderate asthma. A total of 177
      children already treated with inhaled corticosteroids, were randomized in a
      double-blind parallel study either to salmeterol 50 microg twice daily
      (BDP400+salm), beclomethasone 200 microg twice daily (BDP800), or placebo
      (BDP400) in addition to beclomethasone 200 microg twice daily. No significant
      differences between groups were found in FEV1, PD20 methacholine, symptom scores,
      and exacerbation rates after 1 yr. Salmeterol resulted in slightly better PEF in
      the first months of treatment. FEV1, and PD20 methacholine significantly improved
      in all groups. After 1 yr mean changes in FEV1, percent predicted were 4.3% (95%
      CI 1.3; 7.2), 5.8% (95% CI 2.9; 8.7), and 4.3% (95% CI 2.1; 6.5) for BDP400+salm,
      BDP800, and BDP400, respectively. Changes in airway responsiveness were 0.60 (95%
      CI 0.05; 1.14), 1.30 (95% CI 0.73; 1. 87), and 0.80 (95% CI 0.33; 1.27) doubling
      doses. Growth was significantly slower in the BDP800 group. We conclude that no
      additional benefit was found of adding either salmeterol or more beclomethasone
      to a daily dose of 400 microg beclomethasone in this group of children with
      excellent compliance of medication.

PMID- 9655733
TI  - Colchicine versus prednisone in the treatment of idiopathic pulmonary fibrosis. A
      randomized prospective study. Members of the Lung Study Group.
AB  - Twenty-six symptomatic subjects with clinical evidence plus either high
      resolution computed tomography (HRCT, n = 25) or open-lung biopsy (OLB, n = 1)
      patterns typical for idiopathic usual interstitial pneumonia (idiopathic UIP)
      were entered into a randomized prospective treatment trial using high-dose
      prednisone (n = 12) versus colchicine (n = 14). The minimum dose of prednisone
      used was 60 mg/d for 1 mo, tapered to 40 mg/d over the second month, tapered to
      40 mg every other day during the third month, with subsequent doses adjusted as
      clinically indicated. The dose of colchicine was 0.6-1.2 mg/d, as tolerated. The
      presence of a rim of subpleural honeycomb change was present in all of the 25
      subjects who had HRCT. Subjects treated with high-dose prednisone alone
      experienced a higher incidence of serious side effects and also exhibited a trend
      (not statistically significant, p = 0.391) to more rapid decline of pulmonary
      function and shortened survival than did those treated with colchicine alone. In
      most subjects with typical clinical and HRCT features of idiopathic UIP, neither
      prednisone nor colchicine resulted in objective improvement, and the disease
      continued to progress in the majority. Colchicine appears to be a safer
      alternative to a trial of high-dose prednisone but may be no different than no
      therapy.

PMID- 9655734
TI  - Antioxidant supplementation and respiratory functions among workers exposed to
      high levels of ozone.
AB  - Ozone exposure has been related to adverse respiratory effects, in particular to
      lung function decrements. Antioxidant vitamins are free-radical scavengers and
      could have a protective effect against photo-oxidant exposure. To evaluate
      whether acute effects of ozone on lung functions could be attenuated by
      antioxidant vitamin supplementation, we conducted a randomized trial using a
      double-blind crossover design. Street workers (n = 47) of Mexico City were
      randomly assigned to take daily a supplement (75 mg vitamin E, 650 mg vitamin C,
      15 mg beta carotene) or a placebo and were followed from March to August 1996.
      Pulmonary function tests were done twice a week at the end of the workday. During
      the follow-up, the mean 1-h maximum ozone level was 123 ppb (SD = 40). During the
      first phase, ozone levels were inversely associated with FVC (beta = -1.60
      ml/ppb), FEV1 (beta = -2.11 ml/ppb), and FEF25-75 (beta = -4.92 ml/ppb) (p <
      0.05) in the placebo group but not in the supplement group. The difference
      between the two groups was significant for FVC, FEV1, and FEF25-75 (p < 0.01).
      During the second phase, similar results were observed, but the lung function
      decrements in the placebo group were smaller, suggesting that the supplementation
      may have had a residual protective effect on the lung. These results need to be
      confirmed in larger supplementation studies.

PMID- 9655735
TI  - Increased expression of high affinity IgE (FcepsilonRI) receptor-alpha chain mRNA
      and protein-bearing eosinophils in human allergen-induced atopic asthma.
AB  - FcepsilonRI receptors play an important role in allergen-induced mediator release
      and antigen presentation by mast cells, basophils, and monocyte/macrophages in
      atopic disorders. The expression of FcepsilonRI by tissue eosinophils in atopic
      asthma after allergen challenge has not been established. For this reason we
      attempted to identify mRNA and protein product + FcepsilonRIalpha eosinophils in
      cytospins made from bronchoalveolar lavage (BAL) from atopic asthmatics (n = 9)
      and nonatopic normal subjects (n = 4) 24 h after segmental challenge with
      allergen or diluent. Messenger RNA for FcepsilonRIalpha was determined using in
      situ hybridization and FcepsilonRIalpha protein expression by immunocytochemistry
      using a mouse monoclonal antibody 22E7. Colocalization of FcepsilonRIalpha
      receptors to eosinophils was performed using chromotrope 2R. When compared with a
      control challenge, segmental challenge with Dermatophagoides pteronyssinus
      induced significant BAL eosinophilia (p = 0.007). The total number of BAL
      FcepsilonRIalpha mRNA and protein-positive cells also increased in asthmatics,
      median values 2 (0.7-7.2) and 11.5 (0.6-65.0) x 10(6) cells (p = 0.02) and 0 (0
      0.3 x 10(6)) and 3.1 x 10(6) (0.45 - 162.5 x 10(6)) cells (p = 0.007),
      respectively, for mRNA and protein. Net increases in FcepsilonRIalpha+ cells
      correlated with the net increases in BAL eosinophils (r = 0.98, p = 0.0001 for
      mRNA and r = 0.72, p = 0.02 for protein). Colocalization studies with chromotrope
      2R revealed that only 4% of FcepsilonRIalpha+ cells were eosinophils after
      control challenge and, in contrast, 85 to 95% of FcepsilonRIalpha+ cells were
      eosinophils after allergen. There were no differences in the numbers of
      FcepsilonRIalpha+ cells or eosinophils in normal control subjects. Our results
      demonstrated that local endobronchial allergen provocation in atopic asthmatics
      results in increased synthesis and expression of FcepsilonRIalpha predominantly
      on BAL eosinophils.

PMID- 9655736
TI  - Effects of rhinovirus infection on hydrogen peroxide- induced alterations of
      barrier function in the cultured human tracheal epithelium.
AB  - To investigate whether rhinovirus infection impairs epithelial barrier functions,
      human rhinovirus 14 (HRV-14) was infected to primary cultures of human tracheal
      epithelial cells and experiments were performed on Day 2 after HRV-14 infection.
      Hydrogen peroxide (H2O2; 3 x 10(-)4 M) increased electrical conductance (G)
      across the epithelial cell sheet measured with Ussing's chamber methods. Exposure
      of the epithelial cells to HRV-14 had no effect on H2O2-induced increases in G
      and [3H]mannitol flux through the cultured epithelium in the control condition,
      but it markedly potentiated H2O2- induced increases in both parameters in IL
      1beta (100 U/ml) pretreated condition. However, pretreatment with TNF-alpha (100
      U/ml) was without effect. IL-1beta enhanced the intercellular adhesion molecule-1
      (ICAM-1) expression assessed by immunohistochemical analysis and susceptibility
      of epithelial cells to HRV-14 infection. An antibody to ICAM-1 inhibited HRV-14
      infection of epithelial cells and abolished H2O2-induced increases in G and
      [3H]mannitol flux in IL-1beta-pretreated epithelial cells with HRV-14 infection.
      These results suggest that rhinovirus infection may reduce barrier functions in
      the airway epithelium in association with upregulation of ICAM-1 expression.

PMID- 9655737
TI  - Computer tomographic assessment of perfluorocarbon and gas distribution during
      partial liquid ventilation for acute respiratory failure.
AB  - The average in vivo chest computed tomographic (CT) attenuation number (air = 
      1,000, soft tissue = 0, perflubron = +2,300 Hounsfield units [HU]) of 10
      ventrodorsal-oriented lung segments was calculated to assess the distribution of
      gas and perflubron in 14 oleic acid lung-injured adult sheep during partial
      liquid ventilation (PLV, n = 7) or gas ventilation (GV, n = 7). Partial liquid
      ventilation was associated with a significant decrease in shunt fraction (PLV =
      40 +/- 12%, GV = 76 +/- 12%, p = 0.004). Computed tomographic attenuation data
      during expiration (HUexp) demonstrated minimal gas aeration in GV animals in the
      dependent (segments 6-10) lung zones (HUexp = -562 +/- 108 for segments 1-5,
      HUexp = -165 +/- 104 for segments 6-10, p = 0.015). During PLV, perflubron was
      predominantly distributed to the dependent lung regions (HUexp = 579 +/- 338 for
      segments 1-5, HUexp = 790 +/- 149 for segments 6-10, p = 0.04). The ratio of the
      inspiratory to expiratory HU (HUinsp/exp) was greater in dependent than
      nondependent regions (mean HUinsp/exp segments 1-5 = 0.56, segments 6-10 = 0.81,
      p = 0.01), indicating that during inspiration relatively more gas than perflubron
      was distributed to the nondependent lung regions. We conclude that during PLV in
      this lung injury model, (1) gas exchange is improved when compared with gas
      ventilation, (2) perflubron is distributed predominantly to the dependent regions
      of the lung, and (3) although gas is distributed throughout the lung with each
      inspiration, more gas than perflubron goes to the nondependent lung regions.

PMID- 9655738
TI  - Inhibitors of elastase in airway lavage samples from ventilated preterm human
      neonates.
AB  - Surplus elastase released from neutrophils during lung injury is balanced mainly
      by alpha1-protease inhibitor (alpha1-PI) and by two acid-resistant inhibitors.
      The latter include mucus protease inhibitor (MPI, also named SLPI, BSI, ALP) and
      elastase-specific inhibitor (ESI or Elafin), but their functional role during the
      neonatal period has not yet been characterized precisely. The saline airway
      lavage samples from neonates intubated for respiratory distress were separated by
      centrifugation into a cellular and a soluble, supernatant fraction and then
      analyzed. During the first 36 h of life (42 neonates, gestational age 24-40 wk),
      elastase activity was confined to the cellular fraction. Thirty percent of the
      acid-resistant inhibitors but almost no alpha1-PI, was cell-associated. In the
      soluble fraction, about 20-30% of the acid-resistant inhibitors was functionally
      active, but only about 10% of alpha1-PI was. In seven infants with a nosocomial
      infection and deterioration during mechanical ventilation, only a very modest
      increase in elastase activity was observed. However, the functional activity of
      the acid-resistant inhibitors was reduced in the soluble fraction, whereas total
      mass remained unchanged. A full assessment of protease and protease inhibitors
      should include the cellular and the soluble lavage compartments.

PMID- 9655739
TI  - Immunization and challenge with toluene diisocyanate decrease tachykinin and
      calcitonin gene-related peptide immunoreactivity in guinea pig central airways.
AB  - Toluene diisocyanate (TDI) is a potent sensitizer that causes occupational asthma
      in a significant proportion of subjects exposed. We used an animal model to
      investigate whether neuropeptide changes occur in the airways of immunized and
      TDI-challenged guinea pigs. Animals were immunized by weekly intradermal
      injections, challenged with TDI (5 to 20 ppb) after the third injection, and
      killed 6 h after exposure. Control guinea pigs received injections of saline.
      Lung tissue was processed immediately and analyzed for nerves using the
      streptavidin-biotin complex peroxidase method with antisera to the neural marker
      protein gene product 9.5 (PGP 9.5), substance P (SP), and calcitonin gene-
      related peptide (CGRP). We also quantified the inflammatory infiltrate in the
      submucosa of central airways, and we measured the serum level of specific IgG and
      IgG1. Specific antibodies against TDI were present only in immunized animals.
      Immunized as compared with nonimmunized animals had a significant increase in
      eosinophils in the submucosa of central airways, and a further increase was
      observed 6 h after TDI challenge. Immunization and TDI challenge did not modify
      the number of mononuclear cells in the submucosa of central airways in both
      nonimmunized and immunized animals. TDI exposure did not change the overall
      innervation in both nonimmunized and immunized animals, but the density of PGP
      9.5-positive nerves was significantly different between nonimmunized and
      immunized TDI-challenged animals. The density of SP-, and CGRP-immunostained
      nerves was significantly lower in immunized TDI-challenged than in nonimmunized
      animals. TDI exposure significantly decreased the density of SP-positive nerves
      in nonimmunized animals. A negative relationship was found between the presence
      of airway inflammation, as indexed by eosinophil cell infiltration, and the
      density of PGP 9.5-, SP-, and CGRP-immunostained nerves. In conclusion, TDI
      produces airway inflammation and neuropeptides changes in the central airways of
      immunized guinea pigs 6 h after TDI challenge. These findings support an
      interaction between tachykinins, inflammatory (i.e., eosinophils) and possibly
      immune cells.

PMID- 9655740
TI  - Effects of rSP-C surfactant on oxygenation and histology in a rat-lung-lavage
      model of acute lung injury.
AB  - We have tested two surfactant preparations with the same phospholipid (PL)
      composition, containing recombinant surfactant protein-C (rSP-C surfactant) and
      without SP-C (plain PL surfactant). The effects of rSP-C surfactant were compared
      with the bovine-derived surfactant preparations Alveofact, bLES, and Infasurf in
      a lung lavage model, with surfactant given 1 h after the last lavage. The effects
      of surfactant treatment on histopathologic changes (e.g., hyaline-membrane
      formation) and improvement of oxygenation were compared with changes in untreated
      controls. The surfactants were given in doses of 25, 50, and 100 mg PL/kg body
      weight. At 120 min after treatment, only the protein-containing surfactants
      showed a statistically significant increasing dose dependence with respect to
      improving oxygenation. The values were 318 +/- 120 mm Hg, 443 +/- 58 mm Hg, and
      480 +/- 43 mm Hg (mean +/- SD) for the three doses of rSP-C surfactant and 105 +/
      81 mm Hg, 100 +/- 69 mm Hg, and 131 +/- 108 mm Hg for the three doses of PL
      surfactant. The respective values for Alveofact were 104 +/- 81 mm Hg, 105 +/- 93
      mm Hg, and 260 +/- 143 mm Hg; for bLES 373 +/- 138 mm Hg, 441 +/- 88 mm Hg, and
      467 +/- 43 mm Hg; and for Infasurf 146 +/- 96 mm Hg, 284 +/- 178 mm Hg, and 436
      +/- 70 mm Hg. The oxygen values of controls remained low, at 74 +/- 46 mm Hg.
      Only the protein-containing surfactants dose-dependently inhibited the formation
      of hyaline membranes. We conclude that rSP-C surfactant is at least as effective
      as bovine-derived surfactants. Furthermore, the data imply that the difference
      between plain PL surfactant preparations and bovine-derived surfactant
      preparations containing both SP-B and SP-C can be overcome by addition of SP-C.

PMID- 9655741
TI  - Developmental changes in lung cGMP phosphodiesterase-5 activity, protein, and
      message.
AB  - During transitional circulation, the pulmonary vascular bed undergoes a rapid and
      profound reduction in both tone and vascular smooth-muscle (VSM) content. 3',5'
      Guanylate cyclic monophosphate (cGMP) is a crucial mediator in the regulation of
      pulmonary vascular resistance (PVR) and VSM proliferation. Hydrolysis of cGMP is
      achieved predominately by cGMP-specific phosphodiesterases (PDEs). Among the cGMP
      specific PDEs, PDE5 is quantitatively prevalent in lung tissue. We have
      investigated the levels of pulmonary PDE5 enzymatic activity, protein, and
      messenger RNA (mRNA) in ovine and mouse lung during perinatal development. We
      report that within 1 h following birth, PDE5 activity, protein, and mRNA levels
      decrease in both species, in a manner that correlates with known decreases in PVR
      in early transition. However, from 4 to 7 d following birth, a secondary increase
      in PDE5 activity, protein, and mRNA occurs in both ovine and mouse lung,
      suggesting a complex regulation of PVR and VSM proliferation in late perinatal
      development. Our data imply that PDE5 may be an important mediator in the
      regulation of PVR in normal and possibly in pathologic states, and may ultimately
      provide a basis for PDE5 inhibitors as a treatment for pulmonary hypertension.

PMID- 9655742
TI  - Long-term particulate and other air pollutants and lung function in nonsmokers.
AB  - The associations between lung function measures (spirometry and peak expiratory
      flow lability) and estimated 20-yr ambient concentrations of respirable
      particles, suspended sulfates, sulfur dioxide, ozone, and indoor particles were
      studied in a sample of 1,391 nonsmokers followed since 1977. Differences in air
      pollutants across the population were associated with decrements of lung
      function. An increase of 54 d/yr when particles < 10 micro(m) in diameter (PM10)
      exceeded 100 microg/m3 was associated with a 7.2% decrement in FEV1, as percent
      of predicted, in males whose parents had asthma, bronchitis, emphysema, or hay
      fever and with increased peak expiratory flow lability of 0.8% for all females
      and 0.6% for all males. An increase in mean SO4 concentration of 1.6 microg/m3
      was associated with a 1.5% decrement in FEV1, as percent of predicted, in all
      males. An increase of 23 ppb of ozone as an 8-h average was associated with a
      6.3% decrement in FEV1, as percent of predicted, in males whose parents had
      asthma, bronchitis, emphysema, or hay fever.

PMID- 9655743
TI  - Upregulation of xanthine oxidase by lipopolysaccharide, interleukin-1, and
      hypoxia. Role in acute lung injury.
AB  - LPS and selected cytokines upregulate xanthine dehydrogenase/xanthine oxidase
      (XDH/XO) in cellular systems. However, the effect of these factors on in vivo
      XDH/XO expression, and their contribution to lung injury, are poorly understood.
      Rats were exposed to normoxia or hypoxia for 24 h after treatment with LPS (1
      mg/kg) and IL-1beta (100 microg/kg) or sterile saline. Lungs were then harvested
      for measurement of XDH/XO enzymatic activity and gene expression, and pulmonary
      edema was assessed by measurement of the wet/dry lung weight ratio (W/D).
      Although treatment with LPS + IL-1beta or hypoxia independently produced a 2-fold
      elevation (p < 0. 05 versus exposure to normoxia and treatment with saline) in
      lung XDH/XO activity and mRNA, the combination of LPS + IL-1beta and hypoxia
      caused a 4- and 3.5-fold increase in these values, respectively. XDH/XO protein
      expression was increased 2-fold by hypoxia alone and 1.3-fold by treatment with
      LPS + IL-1beta alone or combination treatment. Compared with normoxic lungs, W/D
      was significantly increased by exposure to hypoxia, LPS + IL-1beta, or
      combination treatment. This increase was prevented by treatment of the animals
      with tungsten, which abrogated lung XDH/XO activity. In conclusion, LPS, IL
      1beta, and hypoxia significantly upregulate lung XDH/XO expression in vivo. The
      present data support a role for this enzyme in the pathogenesis of acute lung
      injury.

PMID- 9655744
TI  - Partitioning of lung and chest-wall mechanics before and after lung-volume
      reduction surgery.
AB  - In the study reported here, we partitioned the mechanics of the respiratory
      system into lung and chest-wall components, using the rapid occlusion technique
      in seven patients with severe emphysema before lung-volume-reduction surgery and
      3 mo later. Patients showed improvements in 6-min walk (p < 0.01) and dyspnea (p
      < 0.05). The resistances of the respiratory system and chest wall were not
      altered by surgery. Ohmic airway resistance did not change, but the component of
      lung resistance (DeltaRL) due to viscoelastic behavior (stress relaxation) and
      time-constant inhomogeneities (pendelluft) decreased in six patients (p < 0.03).
      Dynamic elastance of the lung (Edyn,L) decreased after surgery (p < 0.02),
      whereas dynamic elastance of the chest wall did not change. The ratio of dynamic
      intrinsic positive end-expiratory pressure (PEEPi) to static PEEPi, which also
      reflects viscoelastic properties and time-constant inhomogeneities, increased
      after surgery (p < 0.05). The decrease in dyspnea was related to the decrease in
      Edyn,L (r = 0.81, p = 0.03), and tended to be related to the decrease in DeltaRL
      (r = 0.71, p = 0. 07). In conclusion, lung-volume-reduction surgery decreased
      dynamic pressure dissipations caused by stress relaxation and time-constant
      inhomogeneities within lung tissue, and it had no effect on the static mechanical
      properties of the chest wall.

PMID- 9655745
TI  - Increased carbon monoxide in exhaled air of subjects with upper respiratory tract
      infections.
AB  - Viral infection may induce the expression of heme oxygenase, resulting in
      increased carbon monoxide (CO) formation. CO may be produced by various cells of
      the upper and lower respiratory tract and may be detected in the exhaled air.
      Therefore, exhaled CO concentrations were measured on a CO monitor by vital
      capacity maneuver in subjects with upper respiratory tract infections (URTIs) and
      in nonsmoking and smoking healthy control subjects. At the time of symptoms of
      URTI, exhaled CO concentrations were 5.6 +/- 0.4 ppm and decreased to 1.0 +/- 0.1
      ppm during recovery. Recovery values of exhaled CO were similar to those in age
      matched nonsmoking healthy control subjects (1.2 +/- 0.3 ppm). Smoking healthy
      control subjects had the highest levels of exhaled CO concentration among the
      groups (18.5 +/- 2.5 ppm). These findings suggest that symptomatic URTIs increase
      the concentration of CO in exhaled air. This may reflect the induction of heme
      oxygenase that has an antiviral effect in the airways.

PMID- 9655746
TI  - Exhaled nitric oxide (NO) is reduced shortly after bronchoconstriction to direct
      and indirect stimuli in asthma.
AB  - Exhaled NO is increased in patients with asthma and may reflect disease severity.
      We examined whether the level of exhaled NO is related to the degree of airway
      obstruction induced by direct and indirect stimuli in asthma. Therefore, we
      measured exhaled NO levels before and during recovery from histamine and
      hypertonic saline (HS) challenge (Protocol 1) or histamine, adenosine 5'
      monophosphate (AMP), and isotonic saline (IS) challenge (Protocol 2) in 11 and in
      nine patients with mild to moderate asthma, respectively. The challenges were
      randomized with a 2-d interval. Exhaled NO and FEV1 were measured before and at
      4, 10, 20, and 30 min after each challenge. NO was measured during a slow VC
      maneuver with a constant expiratory flow of (0.05 x FVC)/s against a resistance
      of 1 to 2 cm H2O. Baseline exhaled NO levels were not significantly different
      between study days in Protocol 1 (mean +/- SD: 4.8 +/- 1.8 ppb [histamine] versus
      5.4 +/- 2.1 ppb [HS], p = 0.4) or in Protocol 2 (7.9 +/- 4.7 ppb [histamine], 8.3
      +/- 5.2 ppb [AMP], and 7.2 +/- 3.7 ppb [IS], p = 0.7). A significant reduction in
      exhaled NO was observed directly after HS (mean +/- SEM: 39.2 +/- 3.9 %fall) and
      AMP challenge (32.3 +/- 7.3 %fall) (MANOVA, p < 0.001), respectively, whereas
      exhaled NO levels tended to decrease after histamine challenge. Isotonic saline
      challenge did not induce changes in exhaled NO (p = 0.7). There was a positive
      correlation between %fall in FEV1 and the %fall in exhaled NO after histamine,
      HS, and AMP challenge as indicated by the mean slope of the within-subject
      regression lines (p <= 0.04). We conclude that acute bronchoconstriction, as
      induced by direct and indirect stimuli, is associated with a reduction in exhaled
      NO levels in asthmatic subjects. This suggests that airway caliber should be
      taken into account when monitoring exhaled NO in asthma.

PMID- 9655747
TI  - Update: future directions for research on diseases of the lung. The American
      Thoracic Society.

PMID- 9655748
TI  - International guidelines for the selection of lung transplant candidates. The
      American Society for Transplant Physicians (ASTP)/American Thoracic
      Society(ATS)/European Respiratory Society(ERS)/International Society for Heart
      and Lung Transplantation(ISHLT).

PMID- 9655749
TI  - Fifty years of the Journal of Applied Physiology.

PMID- 9655750
TI  - Invited editorial on "Pennes' 1948 paper revisited".

PMID- 9655751
TI  - Pennes' 1948 paper revisited.
AB  - A paper published by Harry H. Pennes in Volume 1 of the Journal of Applied
      Physiology defined the theoretical basis for a considerable body of analysis
      performed by many investigators during the ensuing half century. However, during
      the past decade, the Pennes' model of heat transfer in perfused tissue has been
      criticized for various reasons, one of which is that his own experimental data
      seemed to be at variance with the model. More specifically, the shape of the mean
      temperature-depth relationship measured by Pennes was distinctly different from
      the shape of the theoretical curve. In this paper, I show that Pennes used an
      inappropriate procedure to analyze his data and that, when the data are analyzed
      in a more rigorous manner, they support his theory. Additional support for
      Pennes' theory is provided by the experimental data of H. Barcroft and O. G.
      Edholm [J. Physiol. (Lond.) 102: 5-20, 1942 and 104: 366-376, 1946], who had
      previously studied cooling of the forearm during immersion in water at various
      temperatures.

PMID- 9655752
TI  - Wallace Fenn and the Journal of Applied Physiology.

PMID- 9655753
TI  - My affair with the JAP.

PMID- 9655754
TI  - Functional diameters of alveolar microvessels at high lung volume in zone II.
AB  - To estimate the functional diameter of alveolar microvessels, we perfused
      isolated rat lungs with fluorescent latex particles (1 diameter/lung) at
      inflation, pulmonary arterial, and left atrial pressures of 25, 30, and 0 cmH2O,
      respectively. We used confocal microscopy to count latex particles within septal
      microvessels and flow cytometry to count particle concentrations in venous
      outflow. We found 1-, 2-, and 4-micron-diameter particles within septal vessels
      of 45 +/- 12, 31 +/- 12, and 25 +/- 9%, respectively, of examined alveoli.
      Particles of 5-micron diameter were absent from septal vessels but were present
      within a small percentage of corner vessels. Particle concentrations in the
      venous outflow for 1-, 2-, 4-, and 5-micron-diameter particles were 54 +/- 28, 67
      +/- 32, 2.2 +/- 0.3, and 0.4 +/- 0.3%, respectively, of the arterial inflow.
      Particles with diameters of 6 or 10 micron were absent from venous outflow. Our
      results suggest that, under these conditions, the functional diameter of the
      septal microvessels is approximately 4 micron and that the diameter of the
      adjacent corner vessels is slightly larger but <6 micron.

PMID- 9655755
TI  - Rat brain VEGF expression in alveolar hypoxia: possible role in high-altitude
      cerebral edema.
AB  - The mechanism by which hypoxia causes high-altitude cerebral edema (HACE) is
      unknown. Tissue hypoxia triggers angiogenesis, initially by expressing vascular
      endothelial growth factor (VEGF), which has been shown to increase extracerebral
      capillary permeability. This study investigated brain VEGF expression in 32 rats
      exposed to progressively severe normobaric hypoxia (9-6% O2) for 0 (control), 3,
      6, or 12 h or 1, 2, 3, or 6 days. O2 concentration was adjusted intermittently to
      the limit of tolerance by activity and intake, but no attempt was made to detect
      HACE. Northern blot analysis demonstrated that two molecular bands of transcribed
      VEGF mRNA (approximately 3.9 and 4.7 kb) were upregulated in cortex and
      cerebellum after as little as 3 h of hypoxia, with a threefold increase peaking
      at 12-24 h. Western blot revealed that VEGF protein was increased after 12 h of
      hypoxia, reaching a maximum in approximately 2 days. The expression of flt-1 mRNA
      was enhanced after 3 days of hypoxia. We conclude that VEGF production in hypoxia
      is consistent with the hypothesis that angiogenesis may be involved in HACE.

PMID- 9655756
TI  - E-C coupling failure in mouse EDL muscle after in vivo eccentric contractions.
AB  - The objectives of this research were to determine the contribution of excitation
      contraction (E-C) coupling failure to the decrement in maximal isometric tetanic
      force (Po) in mouse extensor digitorum longus (EDL) muscles after eccentric
      contractions and to elucidate possible mechanisms. The left anterior crural
      muscles of female ICR mice (n = 164) were injured in vivo with 150 eccentric
      contractions. Po, caffeine-, 4-chloro-m-cresol-, and K+-induced contracture
      forces, sarcoplasmic reticulum (SR) Ca2+ release and uptake rates, and
      intracellular Ca2+ concentration ([Ca2+]i) were then measured in vitro in injured
      and contralateral control EDL muscles at various times after injury up to 14
      days. On the basis of the disproportional reduction in Po (approximately 51%)
      compared with caffeine-induced force (approximately 11-21%), we estimate that E-C
      coupling failure can explain 57-75% of the Po decrement from 0 to 5 days
      postinjury. Comparable reductions in Po and K+-induced force (51%), and minor
      reductions (0-6%) in the maximal SR Ca2+ release rate, suggest that the E-C
      coupling defect site is located at the t tubule-SR interface immediately after
      injury. Confocal laser scanning microscopy indicated that resting [Ca2+]i was
      elevated and peak tetanic [Ca2+]i was reduced, whereas peak 4-chloro-m-cresol
      induced [Ca2+]i was unchanged immediately after injury. By 3 days postinjury, 4
      chloro-m-cresol-induced [Ca2+]i became depressed, probably because of decreased
      SR Ca2+ release and uptake rates (17-31%). These data indicate that the decrease
      in Po during the first several days after injury primarily stems from a failure
      in the E-C coupling process.

PMID- 9655757
TI  - Reduced leg blood flow during dynamic exercise in older endurance-trained men.
AB  - It is currently unclear whether aging alters the perfusion of active muscles
      during large-muscle dynamic exercise in humans. To study this issue, direct
      measurements of leg blood flow (femoral vein thermodilution) and systemic
      arterial pressure during submaximal cycle ergometry (70, 140, and 210 W) were
      compared between six younger (Y; 22-30 yr) and six older (O; 55-68 yr)
      chronically endurance-trained men. Whole body O2 uptake, ventilation, and
      arterial and femoral venous samples for blood-gas, catecholamine, and lactate
      determinations were also obtained. Training duration (min/day), estimated leg
      muscle mass (dual-energy X-ray absorptiometry; Y, 21.5 +/- 1.2 vs. O, 19.9 +/-
      0.9 kg), and blood hemoglobin concentration (Y, 14.9 +/- 0.4 vs. O, 14.7 +/- 0.2
      g/dl) did not significantly differ (P > 0.05) between groups. Leg blood flow, leg
      vascular conductance, and femoral venous O2 saturation were approximately 20-30%
      lower in the older men at each work rate (all P < 0.05), despite similar levels
      of whole body O2 uptake. At 210 W, leg norepinephrine spillover rates and femoral
      venous lactate concentrations were more than twofold higher in the older men.
      Pulmonary ventilation was also higher in the older men at 140 (+24%) and 210
      (+39%) W. These results indicate that leg blood flow and vascular conductance
      during cycle ergometer exercise are significantly lower in older endurance
      trained men in comparison to their younger counterparts. The mechanisms
      responsible for this phenomenon and the extent to which they operate in other
      groups of older subjects deserve further attention.

PMID- 9655758
TI  - Peak power output is maintained in rabbit psoas and rat soleus single muscle
      fibers when CTP replaces ATP.
AB  - The chemomechanical coupling mechanism in striated muscle contraction was
      examined by changing the nucleotide substrate from ATP to CTP. Maximum shortening
      velocity [extrapolation to zero force from force-velocity relation (Vmax) and
      slope of slack test plots (V0)], maximum isometric force (Po), power, and the
      curvature of the force-velocity curve [a/Po (dimensionless parameter inversely
      related to the curvature)] were determined during maximum Ca2+-activated isotonic
      contractions of fibers from fast rabbit psoas and slow rat soleus muscles by
      using 0.2 mM MgATP, 4 mM MgATP, 4 mM MgCTP, or 10 mM MgCTP as the nucleotide
      substrate. In addition to a decrease in the maximum Ca2+-activated force in both
      fiber types, a change from 4 mM ATP to 10 mM CTP resulted in a decrease in Vmax
      in psoas fibers from 3.26 to 1.87 muscle length/s. In soleus fibers, Vmax was
      reduced from 1.94 to 0.90 muscle length/s by this change in nucleotide.
      Surprisingly, peak power was unaffected in either fiber type by the change in
      nucleotide as the result of a three- to fourfold decrease in the curvature of the
      force-velocity relationship. The results are interpreted in terms of the Huxley
      model of muscle contraction as an increase in f1 and g1 coupled to a decrease in
      g2 (where f1 is the rate of cross-bridge attachment and g1 and g2 are rates of
      detachment) when CTP replaces ATP. This adequately accounts for the observed
      changes in Po, a/Po, and Vmax. However, the two-state Huxley model does not
      explicitly reveal the cross-bridge transitions that determine curvature of the
      force-velocity relationship. We hypothesize that a nucleotide-sensitive
      transition among strong-binding cross-bridge states following Pi release, but
      before the release of the nucleotide diphosphate, underlies the alterations in
      a/Po reported here.

PMID- 9655759
TI  - Thermogenesis in newborn rats after prenatal or postnatal hypoxia.
AB  - Oxygen consumption (VO2) was measured in normoxia as ambient temperature (Ta) was
      lowered from 40 to 15 degrees C, at the rate of 0.5 degrees C/min
      (thermoneutrality approximately 33 degrees C). In 2-day-old rats born in hypoxia
      after hypoxic gestation, the Ta-VO2 relationship was as in controls; their
      interscapular brown adipose tissue (IBAT) was hypoplastic (less proteins and
      DNA), with lower concentration of the mitochondrial uncoupling protein
      thermogenin. In 8-day-old rats exposed to hypoxia postnatally (day 2 to day 8),
      at any Ta below thermoneutrality VO2 was higher than in controls; also, in this
      group IBAT was hypoplastic with decreased thermogenin. Additional measurements
      under various experimental conditions indicated that the increased thermogenic
      capacity was not explained by the smaller body mass and increased blood oxygen
      content or by the eventuality of intermittent cold stimuli during the chronic
      hypoxia. On the other hand, chronic hypercapnia (3% CO2 in normoxia, from day 2
      to day 8) also resulted in increased normoxic thermogenesis. We conclude that
      chronic hypoxia in the perinatal period 1) reduces IBAT mass and thermogenin
      concentration and 2) can increase the newborn's thermogenic capacity because of
      stress-related mechanisms not specific to hypoxia.

PMID- 9655760
TI  - Dissociation between hysteresivity and tension in constricted tracheal and
      parenchymal strips.
AB  - The object of this study was to investigate how changes in the contractile state
      of smooth muscle would modify oscillatory mechanics of tracheal muscle and lung
      parenchyma during agonist challenge. Guinea pig tracheal and parenchymal lung
      strips were suspended in an organ bath. Measurements of length (L) and tension
      (T) were recorded during sinusoidal oscillations under baseline conditions and
      after challenge with 1 mM ACh. Measurements were also obtained in strips
      pretreated with the calmodulin inhibitor calmidazolium (Cmz) or staurosporine
      (Stauro), a protein kinase C inhibitor. Elastance (E) and resistance (R) were
      calculated by fitting changes in T, L, and DeltaL/Deltat to the equation of
      motion. Hysteresivity (eta) was obtained from the following equation: eta =
      (R/E)2pif, where f is frequency. Finally, maximal unloaded shortening velocity
      during electrical field stimulation was measured in Cmz-pretreated and control
      tracheal strips. In tracheal strips, pretreatment with Cmz caused a significant
      decrease in the eta response to ACh challenge and in maximal unloaded shortening
      velocity measured during electrical field stimulation; Stauro decreased the T, E,
      and R response to ACh. In parenchymal strips, Cmz decreased the eta response,
      whereas Stauro had no effect. These results suggest that modifications in the
      contractile state of the smooth muscle are reflected in changes in the hysteretic
      behavior and that T and eta may be controlled independently. Second, inasmuch as
      changes in eta were similar in parenchymal and tracheal strips, the contractile
      element is implicated as the structure responsible for constriction-induced
      changes in the mechanical behavior of the lung periphery.

PMID- 9655761
TI  - Differences in rat skeletal muscles after incline and decline running.
AB  - Rats were trained for 5 days by running on either an inclined or declined
      treadmill. Three days later, the rats were anesthetized, and angle-torque curves
      were plotted for the vastus intermedius muscles. The maximum active torque was
      generated at significantly greater muscle lengths for muscles from decline
      trained rats compared with incline-trained rats. Sixteen muscles were then fixed
      and acid digested, and fiber lengths and sarcomere lengths were measured. The
      estimated average number of sarcomeres in series was greater in muscle fibers
      from decline-trained animals. Fourteen other muscles underwent a test series of
      lengthening contractions, all from the same knee angle. Torque fell less and the
      optimum angle shifted less for muscles from decline-trained animals, showing that
      the decline-trained muscles were more resistant to changes in mechanical
      parameters that indicate damage. These results support but do not prove the
      proposal that the lesser damage from a series of eccentric contractions seen in
      muscles trained by prior eccentric contractions is due to a greater number of
      sarcomeres in series.

PMID- 9655762
TI  - Catecholaminergic modulation of respiratory rhythm in an in vitro turtle brain
      stem preparation.
AB  - An in vitro brain stem preparation from adult turtles was used to determine
      effects of dopamine (DA) and norepinephrine (NE) on the pattern of respiratory
      motor output recorded from hypoglossal nerve roots (XII). Bath-applied DA (10-200
      microM) increased the frequency of respiratory bursts (peaks) from 0.9 +/- 0.2 to
      2.4 +/- 0.3 (SE) peaks/min, resulting in a 99 +/- 9% increase in neural minute
      activity. R[+]-SCH-23390 (10 microM, D1 antagonist) and eticlopride (20 microM,
      D2 antagonist) attenuated the DA-mediated increase in peak frequency by 52 and
      59%, respectively. On the other hand, the DA-receptor agonists apomorphine (D1,
      D2), quinelorane (D2), and SKF-38393 (D1) had no effect on peak frequency.
      Prazosin, an alpha1-adrenergic antagonist (250 nM) abolished the DA-mediated
      frequency increase. Although NE (10-200 microM) and phenylephrine (10-200 microM,
      alpha1-adrenergic agonist) increased peak frequency from 0.5 +/- 0.1 to 1.2 +/-
      0.3 peaks/min and from 0.6 +/- 0.1 to 1. 0 +/- 0.2 peaks/min, respectively, these
      effects were not as large as that with DA alone. The data suggest that both
      dopaminergic and adrenergic receptor activation in the brain stem increase
      respiratory frequency in turtles, but the DA receptor-mediated increase is
      dependent on coactivation of alpha1-adrenergic receptors.

PMID- 9655763
TI  - Cadaver validation of skeletal muscle measurement by magnetic resonance imaging
      and computerized tomography.
AB  - Magnetic resonance imaging (MRI) and computerized tomography (CT) are promising
      reference methods for quantifying whole body and regional skeletal muscle mass.
      Earlier MRI and CT validation studies used data-acquisition techniques and data
      analysis procedures now outdated, evaluated anatomic rather than adipose tissue
      free skeletal muscle (ATFSM), studied only the relatively large thigh, or found
      unduly large estimation errors. The aim of the present study was to compare arm
      and leg ATFSM cross-sectional area estimates (cm2) by using standard MRI and CT
      acquisition and image-analysis methods with corresponding cadaver estimates. A
      second objective was to validate MRI and CT measurements of adipose tissue
      embedded within muscle (interstitial adipose tissue) and surrounding muscle
      (subcutaneous adipose tissue). ATFSM area (n = 119) by MRI [38.9 +/- 22.3 (SD)
      cm2], CT (39.7 +/- 22.8 cm2), and cadaver (39.5 +/- 23.0 cm2) were not different
      (P > 0.001), and both MRI and CT estimates of ATFSM were highly correlated with
      corresponding cadaver values [MRI: r = 0.99, SE of estimate (SEE) 3.9 cm2, P <
      0.001; and CT: r = 0.99, SEE = 3.8 cm2, P < 0.001]. Similarly good results were
      observed between MRI- and CT-measured vs. cadaver-measured interstitial and
      subcutaneous adipose tissue. For MRI-ATFSM the intraobserver correlation for
      duplicate measurements in vivo was 0. 99 [SEE = 8.7 cm2 (2.9%), P < 0.001]. These
      findings strongly support the use of MRI and CT as reference methods for
      appendicular skeletal muscle, interstitial and subcutaneous adipose tissue
      measurement in vivo.

PMID- 9655764
TI  - Asymmetry in reflex responses of nasal muscles in anesthetized guinea pigs.
AB  - Nasal reflexes elicited by mechanical or electrical stimulation of nasal
      afferents were studied in anesthetized guinea pigs. Probing the nasal cavity of
      one side evoked a greater activation of the contralateral than the ipsilateral
      nasal muscles and, occasionally, sneezing. Similarly, electrical stimulation of
      the ethmoidal nerve often caused sneezing, with a greater activation of the nasal
      muscles and a greater increase in resistance on the contralateral side.
      Asymmetrical activation of the nasal muscles in response to mechanical stimuli
      induces asymmetrical airflows, especially during sneezing, between the two sides
      of the nasal cavity. Most of the expired air is forcibly blown out through the
      ipsilateral nostril, thus improving the elimination of irritants from the nose.

PMID- 9655765
TI  - Potentiation of hypoxic ventilatory response by hyperoxia in the conscious rat:
      putative role of nitric oxide.
AB  - In humans, the hypoxic ventilatory response (HVR) is augmented when preceded by a
      short hyperoxic exposure (Y. Honda, H. Tani, A. Masuda, T. Kobayashi, T. Nishino,
      H. Kimura, S. Masuyama, and T. Kuriyama. J. Appl. Physiol. 81: 1627-1632, 1996).
      To examine whether neuronal nitric oxide synthase (nNOS) is involved in such
      hyperoxia-induced HVR potentiation, 17 male Sprague-Dawley adult rats underwent
      hypoxic challenges (10% O2-5% CO2-balance N2) preceded either by 10 min of room
      air (-O2) or of 100% O2 (+O2). At least 48 h later, similar challenges were
      performed after the animals received the selective nNOS inhibitor 7-nitroindazole
      (25 mg/kg ip). In -O2 runs, minute ventilation (VE) increased from 121.3 +/- 20.5
      (SD) ml/min in room air to 191.7 +/- 23.8 ml/min in hypoxia (P < 0.01). After
      +O2, VE increased from 114.1 +/- 19.8 ml/min in room air to 218.4 +/- 47. 0
      ml/min in hypoxia (+O2 vs. -O2: P < 0.005, ANOVA). After 7-nitroindazole
      administration, HVR was not affected in the -O2 treatment group with VE
      increasing from 113.7 +/- 17.8 ml/min in room air to 185.8 +/- 35.0 ml/min in
      hypoxia (P < 0.01). However, HVR potentiation in +O2-exposed animals was
      abolished (111.8 +/- 18. 0 ml/min in room air to 184.1 +/- 35.6 ml/min in
      hypoxia; +O2 vs. -O2: P not significant). We conclude that in the conscious rat
      nNOS activation mediates essential components of the HVR potentiation elicited by
      a previous short hyperoxic exposure.

PMID- 9655766
TI  - Glycogen supercompensation masks the effect of a traininginduced increase in GLUT
      4 on muscle glucose transport.
AB  - Endurance exercise training induces a rapid increase in the GLUT-4 isoform of the
      glucose transporter in muscle. In fasted rats, insulin-stimulated muscle glucose
      transport is increased in proportion to the increase in GLUT-4. There is evidence
      that high muscle glycogen may decrease insulin-stimulated glucose transport. This
      study was undertaken to determine whether glycogen supercompensation interferes
      with the increase in glucose transport associated with an exercise-induced
      increase in GLUT-4. Rats were trained by means of swimming for 6 h/day for 2
      days. Rats fasted overnight after the last exercise bout had an approximately
      twofold increase in epitrochlearis muscle GLUT-4 and an associated approximately
      twofold increase in maximally insulin-stimulated glucose transport activity.
      Epitrochlearis muscles of rats fed rodent chow after exercise were glycogen
      supercompensated (86.4 +/- 4.8 micromol/g wet wt) and showed no significant
      increase in maximally insulin-stimulated glucose transport above the sedentary
      control value despite an approximately twofold increase in GLUT-4. Fasting
      resulted in higher basal muscle glucose transport rates in both sedentary and
      trained rats but did not significantly increase maximally insulin-stimulated
      transport in the sedentary group. We conclude that carbohydrate feeding that
      results in muscle glycogen supercompensation prevents the increase in maximally
      insulin-stimulated glucose transport associated with an exercise training-induced
      increase in muscle GLUT-4.

PMID- 9655767
TI  - Spaceflight modulates insulin-like growth factor binding proteins and
      glucocorticoid receptor in osteoblasts.
AB  - Rat osteoblasts were cultured for 4 or 5 days during a Space Shuttle mission.
      After 20-h treatment with 1alpha,25-dihydroxyvitamin D3, conditioned media were
      harvested and cellular DNA and/or RNA were fixed on board. The insulin-like
      growth factor binding protein (IGF BP)-3 levels in the media were three- and
      tenfold higher than in ground controls on the fourth and fifth flight days, as
      quantitated by Western ligand blotting and radioimmunoassay, respectively. The
      increased IGF BP-3 protein levels correlated with two- to threefold elevation of
      IGF BP-3 mRNA levels, obtained by reverse transcription-polymerase chain
      reaction. The IGF BP-5 mRNA levels in flight cultures were 33-69% lower than in
      ground controls. The IGF BP-4 mRNA levels in flight cultures were 75% lower than
      in ground controls on the fifth day but were not different on the fourth day. The
      glucocorticoid receptor mRNA levels in flight cultures were increased by three-
      to eightfold on the fourth and fifth days compared with levels in ground
      controls. These data suggest potential mechanisms underlying spaceflight-induced
      osteopenia.

PMID- 9655768
TI  - Human skeletal muscle carnitine palmitoyltransferase I activity determined in
      isolated intact mitochondria.
AB  - This study was designed to compare the activity of skeletal muscle carnitine
      palmitoyltransferase I (CPT I) in trained and inactive men (n = 14) and women (n
      = 12). CPT I activity was measured in intact mitochondria, isolated from needle
      biopsy vastus lateralis muscle samples ( approximately 60 mg). The variability of
      CPT I activity determined on two biopsy samples from the same leg on the same day
      was 4.4, whereas it was 7.0% on two biopsy samples from the same leg on different
      days. The method was sensitive to the CPT I inhibitor malonyl-CoA (88%
      inhibition) and therefore specific for CPT I activity. The mean CPT I activity
      for all 26 subjects was 141.1 +/- 10.6 micromol . min-1 . kg wet muscle (wm)-1
      and was not different when all men vs. all women (140.5 +/- 15.7 and 142.2 +/-
      14.5 micromol . min-1 . kg wm-1, respectively) were compared. However, CPT I
      activity was significantly higher in trained vs. inactive subjects for both men
      (176.2 +/- 21.1 vs. 104.1 +/- 13.6 micromol . min-1 . kg wm-1) and women (167.6
      +/- 14.1 vs. 91.2 +/- 9.5 micromol . min-1 . kg wm-1). CPT I activity was also
      significantly correlated with citrate synthase activity (all subjects, r = 0.76)
      and maximal oxygen consumption expressed in milliliters per kilogram per minute
      (all subjects, r = 0.69). The results of this study suggest that CPT I activity
      can be accurately and reliably measured in intact mitochondria isolated from
      human muscle biopsy samples. CPT I activity was not affected by gender, and
      higher activities in aerobically trained subjects appeared to be the result of
      increased mitochondrial content in both men and women.

PMID- 9655769
TI  - Effects of caffeine on blood pressure, heart rate, and forearm blood flow during
      dynamic leg exercise.
AB  - This study examined the acute effects of caffeine on the cardiovascular system
      during dynamic leg exercise. Ten trained, caffeine-naive cyclists (7 women and 3
      men) were studied at rest and during bicycle ergometry before and after the
      ingestion of 6 mg/kg caffeine or 6 mg/kg fructose (placebo) with 250 ml of water.
      After consumption of caffeine or placebo, subjects either rested for 100 min
      (rest protocol) or rested for 45 min followed by 55 min of cycle ergometry at 65%
      of maximal oxygen consumption (exercise protocol). Measurement of mean arterial
      pressure (MAP), forearm blood flow (FBF), heart rate, skin temperature, and
      rectal temperature and calculation of forearm vascular conductance (FVC) were
      made at baseline and at 20-min intervals. Plasma ANG II was measured at baseline
      and at 60 min postingestion in the two exercise protocols. Before exercise,
      caffeine increased both systolic blood pressure (17%) and MAP (11%) without
      affecting FBF or FVC. During dynamic exercise, caffeine attenuated the increase
      in FBF (53%) and FVC (50%) and accentuated exercise-induced increases in ANG II
      (44%). Systolic blood pressure and MAP were also higher during exercise plus
      caffeine; however, these increases were secondary to the effects of caffeine on
      resting blood pressure. No significant differences were observed in heart rate,
      skin temperature, or rectal temperature. These findings indicate that caffeine
      can alter the cardiovascular response to dynamic exercise in a manner that may
      modify regional blood flow and conductance.

PMID- 9655770
TI  - Effects of posture on cardiovascular responses to lower body positive pressure at
      rest and during dynamic exercise.
AB  - We tested the hypothesis that cardiovascular responses to lower body positive
      pressure (LBPP) would be dependent on the posture of the subject and also on the
      background condition (rest or exercise). We measured heart rate (HR), mean
      arterial blood pressure (MAP), and cardiac stroke volume in eight subjects at
      rest and during cycle ergometer exercise (76 +/- 3 W) with and without LBPP (25,
      50, and 75 mmHg) in the supine and upright positions. At rest, the increase in
      MAP was proportional to the increase in LBPP and was greater in the supine (6 +/-
      2, 15 +/- 3, and 26 +/- 3 mmHg) than in the upright (2 +/- 3, 9 +/- 3, and 17 +/-
      3 mmHg) position. During dynamic exercise, the increases in MAP evoked by 25, 50,
      and 75 mmHg LBPP were greater in the supine (13 +/- 2, 28 +/- 3, and 40 +/- 3
      mmHg) than in the upright (7 +/- 3, 12 +/- 3, and 25 +/- 3 mmHg) position. We
      conclude that the systemic pressure response to LBPP is clearly dependent on the
      body position, with the larger pressure responses being associated with the
      supine position both at rest and during dynamic leg exercise.

PMID- 9655771
TI  - Exercise training enhances adrenergic constriction and dilation in the rat
      spinotrapezius muscle.
AB  - Treadmill training increases functional vasodilation in the rat spinotrapezius
      muscle, although there is no acute increase in blood flow and no increase in
      oxidative capacity. To assess concurrent changes in vascular reactivity, we
      measured arterial diameters in the spinotrapezius muscle of sedentary (Sed) and
      treadmill-trained (Tr; 9-10 wk; terminal intensity 30 m/min, 1.5 degrees incline,
      for 90 min) rats during iontophoretic application of norepinephrine, epinephrine
      (Epi), and H+ (HCl) and during superfusion with adenosine. Terminal-feed arteries
      and first-order arterioles in Tr rats constricted more than those in Sed rats at
      the higher current doses of norepinephrine and Epi. In contrast, at low-current
      doses of Epi, first- and second-order arterioles dilated in Tr but not in Sed
      rats. The vascular responses to HCl were highly variable, but second-order
      arterioles of Tr rats constricted more than those of Sed rats at intermediate
      current doses. There were no significant differences between Sed and Tr rats in
      the vascular responses to adenosine. Both adrenergic vasodilation and
      vasoconstriction were enhanced in the spinotrapezius muscle of Tr rats, and
      enhanced adrenergic vasodilation may contribute to increased functional
      vasodilation. These observations further demonstrate vascular adaptations in
      "nontrained" skeletal muscle tissues.

PMID- 9655772
TI  - Thermoregulatory reflexes and cutaneous active vasodilation during heat stress in
      hypertensive humans.
AB  - During dynamic exercise in the heat, increases in skin blood flow are attenuated
      in hypertensive subjects when compared with normotensive subjects. We studied
      responses to passive heat stress (water-perfused suits) in eight hypertensive and
      eight normotensive subjects. Forearm blood flow was measured by venous-occlusion
      plethysmography, mean arterial pressure (MAP) was measured by Finapres, and
      forearm vascular conductance (FVC) was calculated. Bretylium tosylate (BT)
      iontophoresis was used to block active vasoconstriction in a small area of skin.
      Skin blood flow was indexed by laser-Doppler flowmetry at BT-treated and
      untreated sites, and cutaneous vascular conductance was calculated. In
      normothermia, FVC was lower in hypertensive than in normotensive subjects (P <
      0.01). During heat stress, FVC rose to similar levels in both groups (P > 0.80);
      concurrent cutaneous vascular conductance increases were unaffected by BT
      treatment (P > 0.60). MAP was greater in hypertensive than in normotensive
      subjects during normothermia (P < 0.05, hypertensive vs. normotensive subjects).
      During hyperthermia, MAP fell in hypertensive subjects but showed no
      statistically significant change in normotensive subjects (P < 0.05, hypertensive
      vs. normotensive subjects). The internal temperature at which vasodilation began
      did not differ between groups (P > 0.80). FVC is reduced during normothermia in
      unmedicated hypertensive subjects; however, they respond to passive heat stress
      in a fashion no different from normotensive subjects.

PMID- 9655773
TI  - Catecholamine effects on lipolysis and blood flow in human abdominal and femoral
      adipose tissue.
AB  - With the use of the microdialysis method, the present study, performed on young,
      healthy, nonobese subjects of both genders, compares the effects of locally
      infused catecholamines on glycerol concentration and blood flow in abdominal
      (Abd) and femoral (Fem) adipose tissue. Physiological activation of the
      sympathetic nervous system through active tilt was also investigated. In both
      genders, extracellular glycerol concentration was higher in Fem than in Abd
      adipose tissue. Local blood flow was lower in Fem than in Abd adipose tissue.
      Isoproterenol perfusion increased extracellular glycerol levels, but no
      differences were found by gender or fat-deposit site. Isoproterenol induced a
      greater increase in local blood flow in Fem adipose tissue in both genders.
      Epinephrine and norepinephrine perfusion increased extracellular glycerol and
      reduced blood flow. No major differences were found according to gender and fat
      deposit site. Active tilt increased plasma glycerol, free fatty acid,
      norepinephrine levels, and extracellular glycerol concentration to the same
      extent whatever the gender and fat deposit. Thus, Fem adipose tissue is
      characterized by a higher extracellular glycerol concentration and a lower blood
      flow than is Abd tissue in men and women. In these tissues, in situ lipolysis and
      local blood flow were similar in response to adrenergic stimulation.

PMID- 9655774
TI  - IGF-I and/or growth hormone preserve diaphragm fiber size with moderate
      malnutrition.
AB  - Resistance to the anabolic effects of growth hormone (GH) occurs with severe
      caloric deficit. This study examined whether moderate caloric deficit (50% of
      daily intake for 7 days) in the adolescent rat exceeds a critical threshold for
      GH action and whether a combination of GH and insulin-like growth factor I (IGF
      I) would have enhanced anabolic effects on the diaphragm (Dia). Five groups of
      rats (4 wk old) were studied: 1) control (Ctl), 2) nutritionally deprived (ND),
      3) ND + GH, 4) ND + IGF-I, and 5) ND + GH + IGF-I. IGF-I was given by continuous
      infusion (200 microg/day). GH was injected subcutaneously (250 microg every 12
      h). Contractile and fatigue properties of the Dia were determined in vitro.
      Quantitative histochemical methods were used to determine Dia fiber type
      proportions, cross-sectional areas, and succinate dehydrogenase activities. The
      body weight of Ctl rats increased 46% compared with 7% in ND animals, whereas
      that of ND rats receiving growth factors was intermediate. Serum IGF-I levels
      were reduced 54% in ND animals and maintained with the provision of growth
      factors. Dia fatigue resistance was improved in ND animals receiving growth
      factors. There were no differences in Dia contractile properties, fiber type
      proportions, or succinate dehydrogenase activities across groups. ND resulted in
      atrophy/growth arrest of all Dia fibers (20-32%) compared with Ctl.
      Administration of IGF-I and/or GH completely prevented atrophy/growth arrest of
      all Dia fibers. No additive or synergistic effects were noted. We propose that
      these growth factors may provide useful short-term adjunctive nutritional support
      in circumstances in which the provision of optimal nutrition may be delayed or
      inadequate.

PMID- 9655775
TI  - Rib cage muscle interaction in airway pressure generation.
AB  - We have previously demonstrated in dogs that the change in airway opening
      pressure (DeltaPao) produced by isolated maximum activation of the parasternal
      intercostal or triangularis sterni muscle in a single interspace, the
      sternomastoids, and the scalenes is proportional to the product of muscle mass
      and the fractional change in muscle length per unit volume increase of the
      relaxed chest wall. In the present study, we have assessed the interactions
      between these muscles by comparing the DeltaPao obtained during simultaneous
      activation of a pair of muscles (measured DeltaPao) to the sum of the DeltaPao
      values obtained during their separate activation (predicted DeltaPao). Measured
      and predicted DeltaPao values were compared for the following pairs of muscles:
      the parasternal intercostals in two interspaces, the parasternal intercostals in
      one interspace and either the sternomastoids or the scalenes, two segments of the
      triangularis sterni, and the interosseous intercostals in two contiguous
      interspaces. For all these pairs, the measured DeltaPao was within approximately
      10% of the predicted value. We therefore conclude that 1) the pressure changes
      generated by the rib cage muscles are essentially additive; and 2) measurements
      of the mass of a particular muscle and of its fractional change in length during
      passive inflation can be used to estimate the potential pressure-generating
      ability of the muscle during coordinated activity as well as during isolated
      activation.

PMID- 9655776
TI  - Human thermoregulatory responses during serial cold-water immersions.
AB  - This study examined whether serial cold-water immersions over a 10-h period would
      lead to fatigue of shivering and vasoconstriction. Eight men were immersed (2 h)
      in 20 degrees C water three times (0700, 1100, and 1500) in 1 day (Repeat). This
      trial was compared with single immersions (Control) conducted at the same times
      of day. Before Repeat exposures at 1100 and 1500, rewarming was employed to
      standardize initial rectal temperature. The following observations were made in
      the Repeat relative to the Control trial: 1) rectal temperature was lower and
      heat debt was higher (P < 0.05) at 1100; 2) metabolic heat production was lower
      (P < 0.05) at 1100 and 1500; 3) subjects perceived the Repeat trial as warmer at
      1100. These data suggest that repeated cold exposures may impair the ability to
      maintain normal body temperature because of a blunting of metabolic heat
      production, perhaps reflecting a fatigue mechanism. An alternative explanation is
      that shivering habituation develops rapidly during serially repeated cold
      exposures.

PMID- 9655777
TI  - Pulmonary emphysema decreases hamster skeletal muscle oxidative enzyme capacity.
AB  - Skeletal muscle oxidative enzyme capacity is impaired in patients suffering from
      emphysema and chronic obstructive pulmonary disease. This effect may result as a
      consequence of the physiological derangements because of the emphysema condition
      or, alternatively, as a consequence of the reduced physical activity level in
      these patients. To explore this issue, citrate synthase (CS) activity was
      measured in selected hindlimb muscles and the diaphragm of Syrian Golden hamsters
      6 mo after intratracheal instillation of either saline (Con, n = 7) or elastase
      [emphysema (Emp); 25 units/100 g body weight, n = 8]. Activity level was
      monitored, and no difference between groups was found. Excised lung volume
      increased with emphysema (Con, 1.5 +/- 0.3 g; Emp, 3.0 +/- 0.3 g, P < 0.002).
      Emphysema significantly reduced CS activity in the gastrocnemius (Con, 45.1 +/-
      2.0; Emp, 39.2 +/- 0.8 micromol . min-1 . g wet wt-1, P < 0.05) and vastus
      lateralis (Con, 48.5 +/- 1.5; Emp, 44.9 +/- 0.8 micromol . min-1 . g wet wt-1, P
      < 0.05) but not in the plantaris (Con, 47.4 +/- 3.9; Emp, 48.0 +/- 2.1 micromol .
      min-1 . g wet wt-1, P < 0.05) muscle. In contrast, CS activity increased in the
      costal (Con, 61.1 +/- 1.8; Emp, 65.1 +/- 1.5 micromol . min-1 . g wet wt-1, P <
      0.05) and crural (Con, 58.5 +/- 2.0; Emp, 65.7 +/- 2.2 micromol . min-1 . g wet
      wt-1, P < 0.05) regions of the diaphragm. These data indicate that emphysema per
      se can induce decrements in the oxidative capacity of certain nonventilatory
      skeletal muscles that may contribute to exercise limitations in the emphysematous
      patient.

PMID- 9655778
TI  - Long-term effects of clenbuterol on diaphragm morphology and contractile
      properties in emphysematous hamsters.
AB  - The aim of the present study was to investigate the effect of chronic long-term
      clenbuterol treatment (1 mg/kg subcutaneously twice a day for 12 wk) on diaphragm
      morphology and function in emphysematous (EH) and normal hamsters (NH).
      Clenbuterol increased body weight, diaphragm weight, and skeletal muscle weight
      in both EH and NH to a similar extent. In the diaphragm, clenbuterol
      significantly increased myosin heavy chain type I, IIa, and IIx muscle fiber
      cross-sectional areas by approximately 35-55% in both EH and NH. This response to
      clenbuterol treatment was not significantly different between EH and NH
      diaphragm. In EH, twitch force (Pt), maximal tetanic force, and force-frequency
      curve were significantly reduced compared with NH. In EH, clenbuterol increased
      Pt by approximately 10%, restoring Pt to NH level. A similar improvement was
      observed in the force-frequency characteristics. Clenbuterol did not alter
      contractile properties in NH. In conclusion, long-term clenbuterol treatment
      resulted in an increased size of all diaphragm muscle fiber types in both NH and
      EH. Clenbuterol completely abolished the reduced force generation induced by
      emphysema.

PMID- 9655779
TI  - Direct measurement of the energy expenditure of physical activity in preterm
      infants.
AB  - The energy cost of physical activity (EEA) has been estimated to account for 5
      17% of total energy expenditure (TEE) in neonates. To directly measure EEA, a
      force plate was developed and validated to measure work outputs ranging from 0.3
      to 40 kcal . kg-1 . day-1. By use of this force plate plus indirect calorimetry,
      TEE and EEA were measured and correlated with five activity states in 24 infants
      with gestational age of 31.6 +/- 0.5 (SE) wk and postnatal age of 24.8 +/- 3.7
      days. TEE and EEA were 69.2 +/- 1.5 and 2.4 +/- 0.2 kcal . kg-1 . day-1,
      respectively. EEA per state was 0.5 +/- 0.0 (quiet sleep), 2.4 +/- 0.2 (active
      sleep), 2.8 +/- 0.4 (quiet awake), 7.5 +/- 0.8 (active awake), and 15.1 +/- 2.3
      (crying) kcal . kg-1 . day-1. This provides the first direct measurement of the
      contribution of physical activity to TEE in preterm infants and will enable
      measurement of caloric expenditure from muscle activity in various disease
      conditions and development of nursing strategies to minimize unnecessary energy
      losses.

PMID- 9655780
TI  - Airway-parenchymal interdependence after airway contraction in rat lung explants.
AB  - The constriction of pulmonary airways is limited by the tethering effect exerted
      by parenchymal attachments. To characterize this tethering effect at the scale of
      intraparenchymal airways, we studied the pattern of parenchymal distortion due to
      bronchoconstriction in a rat lung explant system. First, we measured the elastic
      modulus under tension for 2% (wt/vol) agarose alone (37.6 +/- 1.5 kPa) and for
      agarose-filled lung (5.7 +/- 1.3 kPa). The latter is similar to the elastic
      modulus of air-filled lung at total lung capacity (4.5-6 kPa) (S. J. Lai-Fook, T.
      A. Wilson, R. E. Hyatt, and J. R. Rodarte. J. Appl. Physiol. 40: 508-513, 1976),
      suggesting that explants can be used as a model of lung tissue distortion.
      Subsequently, confocal microscopic images of fluorescently labeled 0.5-mm-thick
      explants prepared from agarose-filled rat lungs inflated to total lung capacity
      (48 ml/kg) were acquired. Images were taken before and after airway constriction
      was induced by direct application of 10 mM methacholine, and the pattern of
      parenchymal distortion was measured from the displacement of tissue landmarks
      identified in each image for 14 explants. The magnitude of the radial component
      of tissue displacement was calculated as a function of distance from the airway
      wall and characterized by a parameter, b, describing the rate at which tissue
      movement decreased with radial distance. The parameter b was 0.994 +/- 0.19 (SE),
      which is close to the prediction of b = 1 of micromechanical modeling (T. A.
      Wilson. J. Appl. Physiol. 33: 472-478, 1972). There was significant variability
      in b, however, which was correlated with the fractional reduction in airway
      diameter (r = 0.496). Additionally, parenchymal distortion showed significant
      torsion with respect to the radial direction. This torsion was similar in
      concentric zones around the airway, suggesting that it originates from
      inhomogeneity in the parenchyma rather than inhomogeneous airway constriction.
      Our results demonstrate the significance of the nonlinear mechanical properties
      of alveolar walls and the anisotropy of the parenchyma in determining the nature
      of airway-parenchymal interdependence.

PMID- 9655781
TI  - Comparisons of two-, three-, and four-compartment models of body composition
      analysis in men and women.
AB  - This study compared the traditional two-compartment (fat mass or FM; fat free
      mass or FFM) hydrodensitometric method of body composition measurement, which is
      based on body density, with three (FM, total body water or TBW, fat free dry
      mass)- and four (FM, TBW, bone mineral mass or BMM, residual)-compartment models
      in highly trained men (n = 12), sedentary men (n = 12), highly trained women (n =
      12), and sedentary women (n = 12). The means and variances for the relative body
      fat (%BF) differences between the two- and three-compartment models [2.2 +/- 1.6
      (SD) % BF; n = 48] were significantly greater (P </= 0.02) than those between the
      three- and four-compartment models (0.2 +/- 0.3% BF; n = 48) for all four groups.
      The three-compartment model is more valid than the two-compartment
      hydrodensitometric model because it controls for biological variability in TBW,
      but additional control for interindividual variability in BMM via the four
      compartment model achieves little extra accuracy. The combined group (n = 48)
      exhibited greater (P < 0.001) FFM densities (1.1075 +/- 0.0049 g/cm3) than the
      hydrodensitometric assumption of 1.1000 g/cm3, which is based on analyses of
      three male cadavers aged 25, 35, and 46 yr. This was primarily because their FFM
      hydration (72.4 +/- 1.1%; n = 48) was lower (P </= 0.001) than the
      hydrodensitometric assumption of 73.72%.

PMID- 9655782
TI  - Developmentally regulated expression of cytochrome-c oxidase isoforms in
      regenerating rat skeletal muscle.
AB  - The developmental expression of tissue-specific isoforms of cytochrome-c oxidase
      (COX) subunit VIII [heart (COX VIII-H) and liver (COX VIII-L)] and the influence
      of innervation were examined in regenerating fast [extensor digitorum longus
      (EDL)] and slow (soleus) muscles. In adult muscles, COX VIII-H was the
      predominant isoform. The COX VIII-L mRNA was expressed 3 days after induction of
      regeneration, and it progressively decreased after 7, 10, 14, and 30 days of
      regeneration in both muscles. In contrast, the expression of COX VIII-H mRNA
      accumulated as myogenesis proceeded to the myotube stage between 7 and 10 days of
      regeneration and progressively increased to near control levels by 30 days. The
      influence of innervation on the expression of COX VIII and alpha-actin isoforms
      was examined in control, innervated, and denervated regenerating muscles at 3 and
      10 days. The relative expression of COX VIII-L mRNA in denervated regenerating
      EDL muscles was significantly greater, while that of COX VIII-H was significantly
      less than in innervated regenerating EDL muscles after 10 days of regeneration.
      Similarly, cardiac alpha-actin mRNA levels were elevated in denervated
      regenerating EDL muscles after 10 days of regeneration. In conclusion, motor
      innervation influences the transition from the COX VIII-L to COX VIII-H isoform
      during myogenesis in regenerating muscles.

PMID- 9655783
TI  - Mechanical work of breathing during maximal voluntary ventilation.
AB  - With the use of the esophageal balloon technique, the working capacity of the
      respiratory muscles was assessed in four normal subjects by measuring the work
      per breath (W) and respiratory power (W) during maximal voluntary ventilation
      with imposed respiratory frequencies (f) ranging from 20 to 273 cycles/min.
      Measurements were made in a body plethysmograph to assess the work wasted as a
      result of alveolar gas compressibility (Wg'). In line with other types of human
      voluntary muscle activity, W decreased with increasing f, whereas W exhibited a
      maximum at f of approximately 100 cycles/min. Up to this f value, Wg' was small
      relative to W. With further increase in f, the Wg'/W ratio increased
      progressively, amounting to 8-22% of W at f of 200 cycles/min.

PMID- 9655784
TI  - Long-range correlations of serial FEV1 measurements in emphysematous patients and
      normal subjects.
AB  - In obstructive lung disease the annual change in lung function is usually
      estimated from serial measurements of forced expiratory volume in 1 s (FEV1).
      Frequent measurements in each patient may not improve this estimate because data
      are not statistically independent; i.e., the measurements are autocorrelated. The
      purpose of this study was to describe the correlation structure in time series of
      FEV1 measurements. Nineteen patients with severe alpha1-antitrypsin deficiency
      (phenotype PiZ) and moderate to severe emphysema and two subjects with normal
      lungs were followed for several years with daily self-administered spirometry.
      FEV1 measurements fulfilling standard criteria were detrended, and the
      autocorrelation profile and the power spectrum were calculated. On average the
      subjects were followed for >3 yr and performed >1,000 acceptable spirometries.
      The autocorrelation of FEV1 measurements in the emphysematous patients was
      approximately 0.35 for short intervals and decreased almost exponentially with a
      half time of 38 days. Between 3 and 4 mo, the autocorrelation function became
      negative. It reached a minimum of -0.1 at approximately 8 mo and then increased
      toward zero over the following 12 mo. The autocorrelation function in the two
      normal subjects showed a similar pattern, but with a faster decay toward zero. In
      the patients, the power spectrum had a peak at 1 cycle/wk and showed a 1/f
      pattern, where f is frequency, with a slope of -0.88 at lower frequencies. We
      conclude that serial spirometric measurements show long-range correlations. The
      practical implication is that FEV1 need not be measured more often than once
      every 3 mo in studies of the long-term trends in lung function.

PMID- 9655785
TI  - Meniscus formation during tracheal instillation of surfactant.
AB  - The method of surfactant instillation into the lungs for treatment of neonatal
      respiratory distress syndrome is an important attribute of delivery, and it may
      determine the overall efficacy of treatment. Previous studies primarily focused
      on the rate at which the bolus is instilled. These findings show that rapid
      injections lead to a more homogenous distribution, whereas slow infusions drain
      into the dependent lung with respect to gravity, resulting in a heterogeneous
      deposition. These results suggest that it is beneficial to form a meniscus, from
      which a more homogenous dispersal can proceed. The objective of the present study
      was to develop a functional criterion for meniscus formation during bolus
      injection. An in vitro experiment was used to examine the clinical setting of
      surfactant instillation. The physical variables examined were the bolus viscosity
      (mu) and density (rho), gravity (g), injection rate (Q), orientation of the
      trachea with respect to gravity (theta), tracheal size (D), surface tension
      (gamma), and catheter size (d). All quantities were varied, except gravity and
      catheter size. Experimental results show that a meniscus will form when NSt > 0.
      004Re2/3, where NSt is Stokes number and Re is Reynolds number, NSt =
      muQ/D4rhogsintheta, a ratio of viscous effects to gravitational effects, and Re =
      rhoQD/d2mu, a ratio of inertial effects to viscous effects. Rapid injections,
      high viscosity, and small inclination with respect to gravity promote meniscus
      formation. These results can be used to refine the guidelines for administration
      of surfactant replacement therapy.

PMID- 9655786
TI  - Repetitive prenatal glucocorticoid therapy reduces oxidative stress in the lungs
      of preterm lambs.
AB  - Repetitive courses of maternal prenatal glucocorticoids are often used in high
      risk pregnancies with threatening preterm labor to induce lung maturation, but
      the effects on the cellular oxidant-antioxidant balance in the fetal lung have
      not been evaluated. We investigated the effect of repetitive treatment with
      glucocorticoids, beginning early in gestation, on oxidative stress in the preterm
      ovine lung. Pregnant ewes were randomized to receive one, two, three, or four
      doses of 0.5 mg/kg betamethasone or saline placebo at 7-day intervals on 104,
      111, 118, and 124 days gestation (n = 11 for each group). All lambs were
      delivered preterm at 125 days gestation, and lung tissue was assayed for
      antioxidant enzymes, lipid hydroperoxides, and carbonyl proteins. Lung manganese
      superoxide dismutase, catalase, and glutathione peroxidase activity increased
      after 1 dose of betamethasone given at 104 days gestation, whereas copper-zinc
      superoxide dismutase activity increased after 2 doses given at 104 and 111 days
      gestation. The activity of all four antioxidant enzymes further increased with
      additional doses and was maximal after four doses of betamethasone. Lung lipid
      hydroperoxide levels and carbonyl protein content decreased stepwise after each
      dose of betamethasone and were lowest after four doses. Repetitive prenatal
      glucocorticoid therapy increases antioxidant enzyme activity and reduces
      oxidative stress in the lungs of preterm lambs, and these effects begin early in
      gestation and persist for 2-3 wk.

PMID- 9655787
TI  - Lack of effect of spaceflight on bone mass and bone formation in group-housed
      rats.
AB  - As part of an experiment to study the role of corticosteroids in bone changes
      during spaceflight, male Sprague-Dawley rats (6 wk old, 165 g body weight) were
      placed in orbit for 17 days, in groups of six, in animal-enclosure modules (AEMs)
      aboard the space shuttle Columbia (STS-78). Control rats were group housed in a
      similar manner in ground-based AEMs or standard vivarium cages. Adrenal
      hypertrophy occurred in flight rats, but bone histomorphometric analyses revealed
      a lack of significant changes in bone mass and bone formation in these animals.
      Cancellous bone volume and osteoblast surface in the proximal tibial metaphysis
      were nearly the same in flight and ground-based rats. Normal levels of cancellous
      bone mass and bone formation were also detected in the lumbar vertebrae and
      femoral necks of flight rats. In the tibial diaphysis, periosteal bone formation
      rate was found to be identical in flight and ground-based rats. The results
      indicate that, under conditions of group housing in AEMs, spaceflight has minimal
      effects on bone mass and bone formation in rapidly growing rats. These findings
      emphasize the need to investigate the importance of rat age, strain, and
      especially housing conditions for studies of the skeletal effects of spaceflight.

PMID- 9655788
TI  - Hysteresis of the nasal pressure-flow relationship during hyperpnea in normal
      subjects.
AB  - Hysteresis of the nasal airway pressure-flow relationship (PFR) is seen during
      hyperpnea, with lower nasal resistance during increasing inspiratory flow than
      during decreasing flow. We hypothesized that the nasal PFR hysteresis arose in
      the nasal vestibule airway because of progressive collapse during the
      inspiration. We measured the inspiratory transnasal and transvestibular PFR for
      one nasal passage in five normal subjects breathing via a nasal mask during
      voluntary hyperventilation, both with voluntary nostril flaring and without
      flaring. The inspiratory hysteresis (IH) was quantified as the ratio of the areas
      under the descending and ascending pressure-flow curves. Flaring reduced the
      vestibular IH from 1.96 +/- 0.06 to 1.15 +/- 0.06 and the nasal IH from 2.05 +/-
      0.13 to 1.28 +/- 0.06 (both P < 0.01). Our results demonstrate that hysteresis
      arises in the compliant vestibule segment of the nasal airway, likely because of
      progressive collapse of the nasal vestibule during inspiration. The findings
      suggest that hysteresis is prevented by voluntary nostril flaring maintained
      throughout inspiration.

PMID- 9655789
TI  - Alae nasi activation decreases nasal resistance during hyperoxic hypercapnia.
AB  - It has been proposed that decreases in nasal resistance (Rn) during hypercapnia
      are entirely due to vasoconstriction in the nasal cavity. We hypothesized that
      alae nasi (AN) muscle activity dilates the nasal vestibule and contributes to the
      decrease in Rn during hypercapnia. Nine normal subjects were studied during
      hyperoxic hypercapnia (HH). Rn and vestibular resistance (Rvest) for one nasal
      passage were measured simultaneously with the AN electromyogram before and after
      nasal decongestion. HH decreased Rvest from 1.6 +/- 0.6 to 0.8 +/- 0.9 cmH2O . l
      1 . s (predecongestant) and from 1.3 +/- 0.8 to 0.6 +/- 0.7 cmH2O . l-1 . s
      (postdecongestant; both P < 0. 01). Nasal decongestant decreased Rn but not
      Rvest. Significant inverse linear relationships between Rvest and AN
      electromyogram were demonstrated for all subjects. We conclude that in normal
      subjects during HH 1) decreases in Rvest are predominantly due to increases in AN
      activity; and 2) decreases in Rn are due to a combination of mucosal
      vasoconstriction and AN activation.

PMID- 9655790
TI  - Neuropeptide Y and Y1-receptor agonists increase blood flow through arteriovenous
      anastomoses in rat tail.
AB  - The purpose of this study was to characterize neuropeptide Y (NPY)-induced
      vasodilation in the rat tail. Sterile surgical technique was used (with
      pentobarbital sodium anesthesia) to equip rats with a jugular catheter and a
      blind-ended thermocouple reentrant tube next to the carotid artery. Tail skin and
      core temperature were measured with thermocouples during experiments. Tail skin
      blood flow was monitored with a laser Doppler flowmeter, and tail total blood
      flow and volume were measured with plethysmography. After baseline data were
      collected, saline, NPY (16, 32, 64, and 128 microg/kg), [Leu31 Pro34]NPY (63.25
      microg/kg), or NPY[13-36] (44.7 microg/kg) was administered intravenously. Tail
      total blood flow, volume, and tail skin temperature increased, whereas tail skin
      blood flow and core temperature decreased in response to both NPY- and the Y1
      receptor agonist [Leu31 Pro34]NPY but not in response to saline or NPY[13-36].
      Studies conducted with the use of color microspheres demonstrated that
      arteriovenous anastomoses are involved in this NPY-induced vasodilation.

PMID- 9655791
TI  - Abnormal oxygen uptake kinetic responses in women with type II diabetes mellitus.
AB  - Persons with type II diabetes mellitus (DM), even without cardiovascular
      complications have a decreased maximal oxygen consumption (VO2 max) and
      submaximal oxygen consumption (VO2) during graded exercise compared with healthy
      controls. We evaluated the hypothesis that change in the rate of VO2 in response
      to the onset of constant-load exercise (measured by VO2-uptake kinetics) was
      slowed in persons with type II DM. Ten premenopausal women with uncomplicated
      type II DM, 10 overweight, nondiabetic women, and 10 lean, nondiabetic women had
      a VO2 max test. On two separate occasions, subjects performed 7-min bouts of
      constant-load bicycle exercise at workloads below and above the lactate threshold
      to enable measurements of VO2 kinetics and heart rate kinetics (measuring rate of
      heart rate rise). VO2 max was reduced in subjects with type II DM compared with
      both lean and overweight controls (P < 0.05). Subjects with type II DM had slower
      VO2 and heart rate kinetics than did controls at constant workloads below the
      lactate threshold. The data suggest a notable abnormality in the cardiopulmonary
      response at the onset of exercise in people with type II DM. The findings may
      reflect impaired cardiac responses to exercise, although an additional defect in
      skeletal muscle oxygen diffusion or mitochondrial oxygen utilization is also
      possible.

PMID- 9655792
TI  - Thermal drive contributes to hyperventilation during exercise in sheep.
AB  - The etiology of exercise hypocapnia is unknown. The contributions of exercise
      intensity (ExInt), lactic acid, environmental temperature, rectal temperature
      (Tre), and physical conditioning to the variance in arterial CO2 tension (PaCO2)
      in the exercising sheep were quantified. We hypothesized that thermal drive
      contributes to hyperventilation. Four unshorn sheep were exercised at
      approximately 30, 50, and 70% of maximal O2 consumption for 30 min, or until
      exhaustion, both before and after 5 wk of physical conditioning. In addition, two
      of the sheep were shorn and exercised at each intensity in a cold (<15 degrees C)
      environment. Tre and O2 consumption were measured continuously. Lactic acid and
      PaCO2 were measured at 5- to 10-min intervals. Data were analyzed by multiple
      regression on PaCO2. During exercise, Tre rose and PaCO2 fell, except at the
      lowest ExInt in the cold environment. Tre explained 77% of the variance in PaCO2,
      and ExInt explained 5%. All other variables were insignificant. We conclude that,
      in sheep, thermal drive contributes to hyperventilation during exercise.

PMID- 9655793
TI  - Red blood cells do not contribute to removal of K+ released from exhaustively
      working forearm muscle.
AB  - K+ released from exercising muscle via K+ channels needs to be removed from the
      interstitium into the blood to maintain high muscle cell membrane potential and
      allow normal muscle contractility. Uptake by red blood cells has been discussed
      as one mechanism that would also serve to regulate red blood cell volume, which
      was found to be constant despite increased plasma osmolality and K+ concentration
      ([K+pl]). We evaluated exercise-related changes in [K+pl], pH, osmolality, mean
      cellular Hb concentration, cell water, and red blood cell K+ concentration during
      exhaustive handgrip exercise. Unidirectional 86Rb+ (K+) uptake by red blood cells
      was measured in media with elevated extracellular K+, osmolarity, and
      catecholamines to simulate particularly those exercise-related changes in plasma
      composition that are known to stimulate K+ uptake. During exercise [K+pl]
      increased from 4.4 +/- 0.7 to 7.1 +/- 0.5 mmol/l plasma water and red blood cell
      K+ concentration increased from 137.2 +/- 6.0 to 144.6 +/- 4.6 mmol/l cell water
      (P </= 0.05), but the intracellular K+-to-mean cellular Hb concentration ratio
      did not change. 86Rb+ uptake by red blood cells was increased by approximately
      20% on stimulation, caused by activation of the Na+-K+ pump and Na+-K+-2Cl-
      cotransport. Results indicate the K+ content of red blood cells did not change as
      cells passed the exhaustively exercising forearm muscle despite the elevated
      [K+pl]. The tendency for an increase in intracellular K+ concentration was due to
      a slight, although statistically not significant, decrease in red blood cell
      volume. K+ uptake, although elevated, was too small to move significant amounts
      of K+ into red blood cells. Our results suggest that red blood cells do not
      contribute to the removal of K+ released from muscle and do not regulate their
      volume by K+ uptake during exhaustive forearm exercise.

PMID- 9655794
TI  - A theoretical study of surfactant and liquid delivery into the lung.
AB  - A computational study is presented for the transport of liquids and insoluble
      surfactant through the lung airways, delivered from a source at the distal end of
      the trachea. Four distinct transport regimes are considered: 1) the instilled
      bolus may create a liquid plug that occludes the large airways but is forced
      peripherally during mechanical ventilation; 2) the bolus creates a deposited film
      on the airway walls, either from the liquid plug transport or from direct
      coating, that drains under the influence of gravity through the first few airway
      generations; 3) in smaller airways, surfactant species form a surface layer that
      spreads due to surface-tension gradients, i.e., Marangoni flows; and 4) the
      surfactant finally reaches the alveolar compartment where it is cleared according
      to first-order kinetics. The time required for a quasi-steady-state transport
      process to evolve and for the subsequent delivery of the dose is predicted.
      Following fairly rapid transients, on the order of seconds, steady-state
      transport develops and is governed by the interaction of Marangoni flow and
      alveolar kinetics. Total delivery time is approximately 24 h for a typical first
      dose. Numerical solutions show that both transit and delivery times are strongly
      influenced by the strength of the preexisting surfactant and the geometric
      properties of the airway network. Delivery times for follow-up doses can increase
      significantly as the level of preexisting surfactant rises.

PMID- 9655795
TI  - Assessment of cutaneous blood flow by using topographical perfusion mapping
      techniques.
AB  - The ability of laser Doppler scanning to reproduce the spatial pattern of
      cutaneous vascular conductance (CVC) in a 6.25-cm2 area of skin was evaluated at
      supine rest (28 degrees C), during thermal stress (cold and heat), and during
      baroreceptor unloading with -40-mmHg lower body negative pressure (LBNP). The
      spatial pattern of resting CVC was similar on 3 different days, varying by 6 +/-
      3%. During cold stress, 89 +/- 2% of the skin area showed a decrease in skin
      blood flow (37 +/- 2%), whereas heat stress increased CVC in 94 +/- 5% of the
      skin area. During LBNP, the pattern of CVC response was not uniform, and
      frequency analysis indicated that 47 +/- 5% of the pixels showed a reduction in
      CVC (>1 SE), 28 +/- 2% of the skin area were unaffected, and the remaining 26 +/-
      5% of the pixels showed some increase in CVC. These data indicate the ability of
      topographical perfusion mapping to provide quantitative and reproducible
      information about the spatial distribution of CVC. In addition, the site-to-site
      variability in reflex control of skin blood flow during LBNP is intriguing and
      requires more rigorous evaluation.

PMID- 9655796
TI  - Differential inspiratory timing is genetically linked to mouse chromosome 3.
AB  - Genetic control of differential inspiratory timing (TI) at baseline has been
      previously demonstrated among inbred mouse strains. The inheritance pattern for
      TI between C3H/HeJ (C3; 188 +/- 3 ms) and C57BL/6J (B6; 111 +/- 2 ms) progenitors
      was consistent with a two-gene model. By using the strain distribution pattern
      for recombinant inbred strains derived from C3 and B6 progenitors, 100%
      concordance was established between TI phenotypes and DNA markers on mouse
      chromosome 3. This genotype-phenotype hypothesis was tested by typing 52 B6C3F2
      (F2) progeny by using simple sequence repeat DNA markers (n = 21) polymorphic
      between C3 and B6 strains on mouse chromosome 3. Linkage analysis compared marker
      genotypes to baseline ventilatory phenotypes by computing log-likelihood values.
      A putative quantitative trait locus located in proximity to D3Mit119 was
      significantly associated with baseline TI phenotypes. At the peak (log-likelihood
      = 3.3), the putative quantitative trait locus determined 25% of the phenotypic
      variance in TI among F2 progeny. In conclusion, this genetic model of ventilatory
      characteristics demonstrated an important linkage between differential baseline
      TI and a candidate genomic region on mouse chromosome 3.

PMID- 9655797
TI  - Effect of sleep/wake state on arterial blood pressure in genetically identical
      mice.
AB  - Genetic determinants may contribute to the large variability in arterial blood
      pressure responses to changes in sleep/wake state in humans. In this study, we
      developed techniques to examine the relationship between sleep/wake state and
      mean arterial pressure (MAP) in unrestrained, genetically identical mice
      (C57BL/6J; n = 9). The left common carotid artery was catheterized, and arterial
      blood gases were analyzed 24-48 h postsurgery to verify normal respiratory and
      metabolic function. The animals were then allowed to cycle naturally through
      sleep/wake states over a 3- to 4-h period while continuous polysomnography and
      arterial pressure measurements were made. The MAP decreased from quiet
      wakefulness to non-rapid-eye-movement sleep (9.8 +/- 1.3 mmHg; P < 0.001) and
      further decreased from non-rapid-eye-movement to rapid-eye-movement sleep (9.7 +/
      1.8 mmHg; P < 0.001). We conclude that the inbred strain of C57BL/6J mice
      exhibits significant and consistent changes in MAP related to sleep/wake state.
      Future studies can compare responses in this strain of mice with those in other
      inbred or transgenic mice to determine whether specific genes regulate arterial
      blood pressure responses to sleep/wake state.

PMID- 9655798
TI  - NF-kappaB induction during in vivo hypoxia in dorsocaudal brain stem of rat:
      effect of MK-801 and L-NAME.
AB  - In the nucleus of the solitary tract, NMDA receptors are critical for the hypoxic
      ventilatory response while neuronal nitric oxide synthase (NOS) modulates the
      late component of this response. Nuclear factor (NF)-kappaB is a ubiquitous
      transcription factor that increases the expression of multiple stress-activated
      genes. We sought to examine temporal changes in expression of NF-kappaB within
      the dorsocaudal brain stem of conscious rats after exposures to 10% O2. Time
      dependent increases in NF-kappaB occurred with hypoxia and peaked at 60 min.
      Pretreatment with the N-methyl-D-aspartate (NMDA)-receptor channel antagonist
      dizocilpine maleate (MK-801) markedly attenuated NF-kappaB complexes during
      hypoxia. In contrast, after NOS inhibition with NG-nitro-L-arginine methyl ester
      (L-NAME), although NF-kappaB was diminished in normoxia, increased NF-kappaB
      expression still occurred with hypoxia. Increased phosphorylation of the NF
      kappaB regulatory unit [inhibitory (I)kappaB] was detected by immunoblotting and
      also peaked at 60 min. Phosphorylation of Ikappa-B during hypoxia was attenuated
      by MK-801 but not by L-NAME. Thus NMDA-receptor activation in the dorsocaudal
      brain stem during hypoxia elicits in NF-kappaB activity marked enhancements that
      are unaffected after NOS blockade.

PMID- 9655799
TI  - Gli2 is required for induction of floor plate and adjacent cells, but not most
      ventral neurons in the mouse central nervous system.
AB  - Induction of the floor plate at the ventral midline of the neural tube is one of
      the earliest events in the establishment of dorsoventral (d/v) polarity in the
      vertebrate central nervous system (CNS). The secreted molecule, Sonic hedgehog,
      has been shown to be both necessary and sufficient for this induction. In
      vertebrates, several downstream components of this signalling pathway have been
      identified, including members of the Gli transcription factor family. In this
      study, we have examined d/v patterning of the CNS in Gli2 mouse mutants. We have
      found that the floor plate throughout the midbrain, hindbrain and spinal cord
      does not form in Gli2 homozygotes. Despite this, motoneurons and ventral
      interneurons form in their normal d/v positions at 9.5 to 12.5 days postcoitum
      (dpc). However, cells that are generated in the region flanking the floor plate,
      including dopaminergic and serotonergic neurons, were greatly reduced in number
      or absent in Gli2 homozygous embryos. These results suggest that early signals
      derived from the notochord can be sufficient for establishing the basic d/v
      domains of cell differentiation in the ventral spinal cord and hindbrain.
      Interestingly, the notochord in Gli2 mutants does not regress ventrally after
      10.5 dpc, as in normal embryos. Finally, the spinal cord of Gli1/Gli2 zinc-finger
      deletion double homozygous mutants appeared similar to Gli2 homozygotes,
      indicating that neither gene is required downstream of Shh for the early
      development of ventral cell fates outside the ventral midline.

PMID- 9655800
TI  - engrailed and polyhomeotic interactions are required to maintain the A/P boundary
      of the Drosophila developing wing.
AB  - Engrailed is a nuclear regulatory protein with essential roles in embryonic
      segmentation and wing morphogenesis. One of its regulatory targets in embryos was
      shown to be the Polycomb group gene, polyhomeotic. We show here that
      transheterozygous adult flies, mutant for both engrailed and polyhomeotic, show a
      gap in the fourth vein. In the corresponding larval imaginal discs, a
      polyhomeotic-lacZ enhancer trap is not normally activated in anterior cells
      adjacent to the anterior-posterior boundary. This intermediary region corresponds
      to the domain of low engrailed expression that appears in the anterior
      compartment, during L3. Several arguments show that engrailed is responsible for
      the induction of polyhomeotic in these cells. The role of polyhomeotic in this
      intermediary region is apparently to maintain the repression of hedgehog in the
      anterior cells abutting the anterior-posterior boundary, since these cells
      ectopically express hedgehog when polyhomeotic is not activated. This leads to
      ectopic expressions first of patched, then of cubitus interruptus and
      decapentaplegic in the posterior compartment, except for the dorsoventral border
      cells that are not affected. Thus posterior cells express a new set of genes that
      are normally characteristic of anterior cells, suggesting a change in the cell
      identity. Altogether, our data indicate that engrailed and polyhomeotic
      interactions are required to maintain the anterior-posterior boundary and the
      posterior cell fate, just prior to the evagination of the wing.

PMID- 9655801
TI  - Morphogenesis of the Drosophila fusome and its implications for oocyte
      specification.
AB  - The Drosophila oocyte develops within a cyst of 16 germline cells interconnected
      by ring canals. Polarized, microtubule-based transport of unknown determinants is
      required for oocyte formation, but whether polarity is established during or
      after cyst formation is not clear. We have analyzed how polarity develops in stem
      cells and dividing cysts by following the growth of the fusome, a vesiculated
      cytoplasmic organelle. Our studies show that the fusome grows by a regular,
      polarized process throughout the stem cell and cyst cell cycles. Each
      polarization cycle begins in mitosis, when the fusome segregates to a single
      daughter cell of each pair. Following mitosis, a 'plug' of fusomal material forms
      in each nascent ring canal and gradually fuses with the pre-existing fusome. In
      stem cells, the ring canal is transient and closes down after the fusome is
      partitioned through it. In dividing cysts, as the fusome plugs move toward the
      pre-existing fusome, their associated ring canals also move, changing the
      geometry of the cyst. At the end of each cycle of cyst growth, the fusome remains
      asymmetrically distributed within the cyst; one of the two cells with four ring
      canals retains a bigger piece of fusome than any other cell, including the other
      cell with four ring canals. Based on these observations, we argue that the oocyte
      is specified at the first cyst division.

PMID- 9655802
TI  - Epithelial-mesenchymal signaling during the regionalization of the chick gut.
AB  - The development of the vertebrate gut requires signaling between the endoderm and
      mesoderm for establishing its normal anteroposterior (AP) axis and for tissue
      specific differentiation. Factors implicated in positional specification of the
      AP regions of the gut include endodermally expressed Sonic hedgehog (Shh),
      mesodermally expressed Bmp4 and members of the Hox gene family. We have
      investigated the roles of these factors during AP regional specification of the
      chick embryonic gut. Early in gut development, the endoderm sends inductive
      signals to the mesoderm. Shh has been implicated as one of these signals. We find
      a differential response to exposure of the inductive influence of Shh along the
      AP axis of the gut. Virally mediated misexpression of Shh results in ectopic
      upregulation of its receptor Ptc and a cellular proliferation throughout the gut
      mesoderm. Although ectopic Shh can induce Bmp4 in the mesoderm of the midgut and
      hindgut, Bmp4 is not induced in the stomach region of the foregut. The stomach
      region has a thicker layer of mesoderm than the rest of the gut suggesting that
      the normal function of Bmp4 could be to limit mesodermal growth in the non
      stomach regions of the gut. Ectopic Bmp4 expression in the stomach results in a
      reduction of the mesodermal component consistent with this hypothesis. In
      addition to the regional restriction on Bmp4 induction, Shh can only induce Hoxd
      13 in the mesoderm of the hindgut. These findings suggest that a prepattern
      exists in the primitive gut mesoderm prior to expression of Shh in the endoderm.
      The gut mesoderm is subsequently responsible for inducing region-specific
      differentiation of its overlying endoderm. We tested the role of Hoxd-13,
      normally restricted in its mesodermal expression to the most posterior region of
      the hindgut (cloaca), in controlling adjacent endodermal differentiation. When
      virally mediated Hoxd-13 is misexpressed in the primitive midgut mesoderm, there
      is a transformation of the endoderm to the morphology and mucin content of the
      hindgut. Thus, the positionally restricted expression of a Hox gene in the gut
      mesoderm influences the inductive signaling that leads to regionally specific
      differentiation of gut endoderm.

PMID- 9655803
TI  - The Shh signalling pathway in tooth development: defects in Gli2 and Gli3
      mutants.
AB  - The expression of genes involved in the Sonic Hedgehog signalling pathway,
      including Shh, Ptc, Smo, Gli1, Gli2 and Gli3, were found to be expressed in
      temporal and spatial patterns during early murine tooth development, suggestive
      of a role in early tooth germ initiation and subsequent epithelial-mesenchymal
      interactions. Of these Ptc, Smo, Gli1, Gli2 and Gli3 were expressed in epithelium
      and mesenchyme whereas Shh was only detected in epithelium. This suggests that
      Shh is involved in both lateral (epithelial-mesenchymal) and planar (epithelial
      epithelial) signalling in early tooth development. Ectopic application of Shh
      protein to mandibular mesenchyme induced the expression of Ptc and Gli1. Addition
      of exogenous Shh protein directly into early tooth germs and adjacent to tooth
      germs, resulted in abnormal epithelial invagination, indicative of a role for Shh
      in epithelial cell proliferation. In order to assess the possible role of this
      pathway, tooth development in Gli2 and Gli3 mutant embryos was investigated. Gli2
      mutants were found to have abnormal development of maxillary incisors, probably
      resulting from a mild holoprosencephaly, whereas Gli3 mutants had no major tooth
      abnormalities. Gli2/Gli3 double homozygous mutants did not develop any normal
      teeth and did not survive beyond embryonic day 14.5; however, Gli2(-/-); Gli3(+/
      ) did survive until birth and had small molars and mandibular incisors whereas
      maxillary incisor development was arrested as a rudimentary epithelial
      thickening. These results show an essential role for Shh signalling in tooth
      development that involves functional redundancy of downstream Gli genes.

PMID- 9655804
TI  - Leafbladeless1 is required for dorsoventrality of lateral organs in maize.
AB  - The maize leafbladeless1 (lbl1) mutant displays a variety of leaf and plant
      phenotypes. The most extreme manifestation in the leaf is the formation of
      radially symmetric, abaxialized leaves due to a complete loss of adaxial cell
      types. Less severe phenotypes, resulting from a partial loss of adaxial cell
      identity, include the formation of ectopic laminae at the boundary between
      abaxialized, mutant sectors on the adaxial leaf surface and the bifurcation of
      leaves. Ectopic laminae and bifurcations arise early in leaf development and
      result in an altered patterning of the leaf along the proximodistal axis, or in
      complete duplication of the developing organ. Leaf-like lateral organs of the
      inflorescences and flowers show similar phenotypes. These observations suggest
      that Lbl1 is required for the specification of adaxial cell identity within
      leaves and leaf-like lateral organs. Lbl1 is also required for the lateral
      propagation of leaf founder cell recruitment, and plays a direct or indirect role
      in the downregulation of the homeobox gene, knotted1, during leaf development.
      Our results suggest that adaxial/abaxial asymmetry of lateral organs is specified
      in the shoot apical meristem, and that formation of this axis is essential for
      marginal, lateral growth and for the specification of points of proximodistal
      growth. Parallels between early patterning events during lateral organ
      development in plants and animals are discussed.

PMID- 9655805
TI  - Differential regulation of T-box and homeobox transcription factors suggests
      roles in controlling chick limb-type identity.
AB  - The wing and the leg of the chick, although homologous structures, have
      characteristic patterns of skeletal elements, muscles, tendons, featherbuds and
      scales. Despite recent advances in understanding the common genetic pathways
      patterning the wing and leg, the molecular nature of the specification of limb
      type identity has remained elusive. Embryological experiments have indicated the
      existence of limb-specific territories in the flank. In the newt, deviation of
      nerves from the limb into the flank can induce ectopic limbs to form from this
      tissue. In the chick, Fibroblast growth factor (FGF)-soaked beads applied to the
      flank can induce ectopic formation of limbs from the surrounding tissue. In both
      cases, the type of limb that forms, either a wing/forelimb or leg/hindlimb, is
      dependent upon the location to which the limb-inducing signal is applied. We have
      isolated and characterised three candidate genes for controlling limb identity in
      the chick. Two T-box transcription factors, cTbx4 and cTbx5, are expressed in a
      restricted manner in the leg bud and wing buds, respectively. cPtx1, a member of
      the Otx-related subclass of paired-type homeodomain proteins, is expressed
      exclusively in the leg bud. Using FGF to induce ectopic limb buds of wing, leg
      and intermediate identity, we show that early expression of cTbx5, cTbx4 and
      cPtx1 in the induced limb buds correlates with later wing- or leg-type identity
      of ectopic limbs. We observe a general correlation between the location of an
      ectopic outgrowth induced by FGF and the identity of the resulting limb but,
      significantly, we report that there is no definitive rostral-caudal level that
      divides the ectopic wing and leg territories.

PMID- 9655806
TI  - Patterning of the follicle cell epithelium along the anterior-posterior axis
      during Drosophila oogenesis.
AB  - Gurken signals from the oocyte to the adjacent follicle cells twice during
      Drosophila oogenesis; first to induce posterior fate, thereby polarising the
      anterior-posterior axis of the future embryo and then to induce dorsal fate and
      polarise the dorsal-ventral axis. Here we show that Gurken induces two different
      follicle cell fates because the follicle cells at the termini of the egg chamber
      differ in their competence to respond to Gurken from the main-body follicle cells
      in between. By removing the putative Gurken receptor, Egfr, in clones of cells,
      we show that Gurken signals directly to induce posterior fate in about 200 cells,
      defining a terminal competence domain that extends 10-11 cell diameters from the
      pole. Furthermore, small clones of Egfr mutant cells at the posterior interpret
      their position with respect to the pole and differentiate as the appropriate
      anterior cell type. Thus, the two terminal follicle cell populations contain a
      symmetric prepattern that is independent of Gurken signalling. These results
      suggest a three-step model for the anterior-posterior patterning of the
      follicular epithelium that subdivides this axis into at least five distinct cell
      types. Finally, we show that Notch plays a role in both the specification and
      patterning of the terminal follicle cells, providing a possible explanation for
      the defect in anterior-posterior axis formation caused by Notch and Delta
      mutants.

PMID- 9655807
TI  - Basal ganglia precursors found in aggregates following embryonic transplantation
      adopt a striatal phenotype in heterotopic locations.
AB  - Transplantation of immature CNS-derived cells into the developing brain is a
      powerful approach to investigate the factors that regulate neuronal position and
      phenotype. CNS progenitor cells dissociated from the embryonic striatum and
      implanted into the brain of embryos of the same species generate cells that
      reaggregate to form easily recognizable structures that we previously called
      clusters and cells that disperse and integrate as single cells into the host
      brain. We sought to determine if the neurons in the clusters differentiate
      according to their final location or acquire a striatal phenotype in heterotopic
      positions. We transplanted dissociated cells from the E14 rat medial and lateral
      ganglionic eminences, either combined or in isolation, into the E16 embryonic rat
      brain. At all time points, we found clusters of BrdU- and DiI-labelled donor
      cells located in the forebrain and hindbrain, without any apparent preference for
      striatum. Immunocytochemical analyses revealed that cells in the clusters
      expressed DARPP-32 and ARPP-21, two antigens typically co-expressed in striatal
      medium-sized spiny neurons. In agreement with observations previously noted by
      several groups, isolated cells integrated into heterologous host areas do not
      express basal ganglia phenotypes. These data imply that immature striatal
      neuronal progenitors exert a community effect on each other that is permissive
      and/or instructive for development of a striatal phenotype in heterotopic
      locations.

PMID- 9655808
TI  - The rough sheath2 gene negatively regulates homeobox gene expression during maize
      leaf development.
AB  - Leaves of higher plants are produced in a sequential manner through the
      differentiation of cells that are derived from the shoot apical meristem. Current
      evidence suggests that this transition from meristematic to leaf cell fate
      requires the down-regulation of knotted1-like homeobox (knox) gene expression. If
      knox gene expression is not repressed, overall leaf shape and cellular
      differentiation within the leaf are perturbed. In order to identify genes that
      are required for the aquisition of leaf cell fates, we have genetically screened
      for recessive mutations that confer phenotypes similar to dominant mutations
      (e.g. Knotted1 and Rough sheath1) that result in the ectopic expression of class
      I knox genes. Independently derived mutations at the rough sheath2 (rs2) locus
      condition a range of pleiotropic leaf, node and internode phenotypes that are
      sensitive to genetic background and environment. Phenotypes include dwarfism,
      leaf twisting, disorganized differentiation of the blade-sheath boundary,
      aberrant vascular patterning and the generation of semi-bladeless leaves. knox
      genes are initially repressed in rs2 mutants as leaf founder cells are recruited
      in the meristem. However, this repression is often incomplete and is not
      maintained as the leaf progresses through developement. Expression studies
      indicate that three knox genes are ectopically or over-expressed in developing
      primordia and in mature leaves. We therefore propose that the rs2 gene product
      acts to repress knox gene expression (either directly or indirectly) and that rs2
      gene action is essential for the elaboration of normal leaf morphology.

PMID- 9655809
TI  - Opl: a zinc finger protein that regulates neural determination and patterning in
      Xenopus.
AB  - In order to study the mechanism of neural patterning in Xenopus, we used
      subtractive cloning to isolate genes activated early during this process. One
      gene isolated was opl, (odd-paired-like) that resembles the Drosophila pair-rule
      gene odd-paired and encodes a zinc finger protein that is a member of the Zic
      gene family. At the onset of gastrulation, opl is expressed throughout the
      presumptive neural plate, indicating that neural determination has begun at this
      stage while, by neurula, opl expression is restricted to the dorsal neural tube
      and neural crest. opl encodes a transcriptional activator, with a carboxy
      terminal regulatory domain, which when removed increases opl activity. opl both
      sensitizes animal cap ectoderm to the neural inducer noggin and alters the
      spectrum of genes induced by noggin, allowing activation of the midbrain marker
      engrailed. Consistent with the later dorsal neural expression of opl, the
      activated form of opl is able to induce neural crest and dorsal neural tube
      markers both in animal caps and whole embryos. In ventral ectoderm, opl induces
      formation of loose cell aggregates that may indicate neural crest precursor
      cells. Aggregates do not express an epidermal marker, indicating that opl
      suppresses ventral fates. Together, these data suggest that opl may mediate
      neural competence and may be involved in activation of midbrain, dorsal neural
      and neural crest fates.

PMID- 9655810
TI  - Src64 is required for ovarian ring canal morphogenesis during Drosophila
      oogenesis.
AB  - The Src family of protein tyrosine kinases have been implicated as important
      regulators of cellular proliferation, differentiation and function. In order to
      understand further the role of Src family kinases, we have generated loss-of
      function mutations in Src64, one of two Src family kinases known in Drosophila
      melanogaster. Animals with reduced Src64 function develop normally and are fully
      viable. However, Src64 female flies have reduced fertility, which is associated
      with the incomplete transfer of cytoplasm from nurse cells to the developing
      oocyte. Analysis of Src64 egg chambers showed defects in the ring canals that
      interconnect the oocyte and its 15 associated nurse cells. Src64 ring canals fail
      to accumulate the high levels of tyrosine phosphorylation that are normally
      present. Despite the reduced tyrosine phosphorylation, known ring canal
      components such as filamentous actin, a ring canal-specific product of the hu-li
      tai shao gene, and the kelch protein localize properly. However, Src64 ring
      canals are reduced in size and frequently degenerate. These results indicate that
      Src64 is required for the proper growth and stability of the ovarian ring canals.

PMID- 9655811
TI  - A subset of notch functions during Drosophila eye development require Su(H) and
      the E(spl) gene complex.
AB  - The Notch signalling pathway is involved in many processes where cell fate is
      decided. Previous work showed that Notch is required at successive steps during
      R8 specification in the Drosophila eye. Initially, Notch enhances atonal
      expression and promotes atonal function. After atonal autoregulation has been
      established, Notch signalling represses atonal expression during lateral
      specification. In this paper we investigate which known components of the Notch
      pathway are involved in each signalling process. Using clonal analysis we show
      that a ligand of Notch, Delta, is required along with Notch for both proneural
      enhancement and lateral specification, while the downstream components Suppressor
      of-Hairless and Enhancer-of-Split are involved only in lateral specification. Our
      data point to a distinct signal transduction pathway during proneural enhancement
      by Notch. Using misexpression experiments we also show that particular Enhancer
      of-split bHLH genes can differ greatly in their contribution to lateral
      specification.

PMID- 9655812
TI  - A role for glutamate and its receptors in the regulation of oligodendrocyte
      development in cerebellar tissue slices.
AB  - We tested the hypothesis that the neurotransmitter glutamate would influence
      glial proliferation and differentiation in a cytoarchitecturally intact system.
      Postnatal day 6 cerebellar slices were maintained in organotypic culture and
      treated with glutamate receptor agonists or antagonists. After dissociation,
      cells were stained with antibodies for different oligodendrocyte developmentally
      regulated antigens. Treatment of the slices with the glutamate receptor agonists
      kainate or alpha -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      significantly decreased the percentage of LB1(+), NG2(+) and O4(+) cells, and
      their bromodeoxyuridine labeling index. The non-N-methyl-D-aspartate glutamate
      receptor antagonist 6,7-dinitroquinoxaline-2,3-dione increased the percentage and
      bromodeoxyuridine labeling of LB1(+), NG2(+) and O4(+) cells. In intact slices,
      RNA levels of the oligodendrocyte gene for 2',3'-cyclic nucleotide 3'
      phosphodiesterase were decreased by kainate and alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid, and increased by 6,7-dinitroquinoxaline-2,3-dione. The
      percentage of astrocytes was not modified by kainate, alpha -amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid or 6, 7-dinitroquinoxaline-2,3-dione. Treatment
      with the N-methyl-D-aspartate receptor antagonist 2-amino-5-phosphonopentanoic
      acid did not alter the percentage of O4(+) cells, nor their proliferation.
      Incubation with the gamma-aminobutyric acid receptor antagonist bicuculline did
      not modify the percentage of LB1(+), A2B5(+) and O4(+) cells. In purified
      cerebellar oligodendrocyte progenitor cells, glutamate receptor agonists blocked
      K+ currents, and inhibited cell proliferation and lineage progression. The K+
      channel blocker tetraethylammonium also inhibited oligodendrocyte progenitor cell
      proliferation. These findings indicate that in rat cerebellar tissue slices: (i)
      glutamate specifically modulates oligodendrocyte but not astrocyte development
      through selective activation of alpha -amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid receptors, and (ii) cell depolarization and blockage of
      voltage-dependent K+ channels is likely to be the triggering mechanism.

PMID- 9655813
TI  - Transgene expression of steel factor in the basal layer of epidermis promotes
      survival, proliferation, differentiation and migration of melanocyte precursors.
AB  - Mutations at the murine dominant white spotting (KitW) and steel (MgfSl) loci,
      encoding c-Kit receptor kinase and its ligand respectively, exert developmental
      defects on hematopoietic cells, melanocytes, germ cells and interstitial cells of
      Cajal. The expression patterns of steel factor (SLF) observed in the skin and
      gonads suggest that SLF mediates a migratory or a chemotactic signal for c-Kit
      expressing stem cells (melanocyte precursors and primordial germ cells). By
      targeting expression of SLF to epidermal keratinocytes in mice, we observed
      extended distribution of melanocytes in a number of sites including oral
      epithelium and footpads where neither melanocytes nor their precursors are
      normally detected. In addition, enlarged pigmented spots of KitW and other
      spotting mutant mice were observed in the presence of the SLF transgene. These
      results provide direct evidence that SLF stimulates migration of melanocytes in
      vivo. We also present data suggesting that SLF does not simply support survival
      and proliferation of melanocytes but also promotes differentiation of these
      cells. Unexpectedly, melanocyte stem cells independent of the c-Kit signal were
      maintained in the skin of the SLF transgenic mice. After the elimination of c-Kit
      dependent melanoblasts by function-blocking anti-c-Kit antibody, these stem cells
      continued to proliferate and differentiate into mature melanocytes. These
      melanoblasts are able to migrate to cover most of the epidermis after several
      months. The SLF transgenic mice described in this report will be useful in the
      study of melanocyte biology.

PMID- 9655814
TI  - Localized changes in apoplastic and cytoplasmic pH are associated with root hair
      development in Arabidopsis thaliana.
AB  - Morphogenesis in plants is characterized by highly regulated cell enlargement.
      However, the mechanisms controlling and localizing regions of growth remain
      essentially unknown. Root hair formation involves the induction of a localized
      cell expansion in the lateral wall of a root epidermal cell. This expanded region
      then enters a second phase of localized growth called tip growth. Root hair
      formation therefore provides a model in which to study the cellular events
      involved in regulating localized growth in plants. Confocal ratio imaging of the
      pH of the cell wall revealed an acidification at the root hair initiation site.
      This acidification was present from the first morphological indications of
      localized growth, but not before, and was maintained to the point where the
      process of root hair initiation ceased and tip growth began. Preventing the wall
      acidification with pH buffers arrested the initiation process but growth resumed
      when the wall was returned to an acidic pH. Cytoplasmic pH was found to be
      elevated from approximately 7.3 to 7. 7 at the initiation site, and this
      elevation coincided with the acidification of the wall. Preventing the localized
      increase in cytoplasmic pH with 10 mM butyrate however did not inhibit either the
      wall acidification or the initiation process. In contrast, there was no
      detectable gradient in pH associated with the apex of tip growing root hairs, but
      both elevated apoplastic pH and butyrate treatment irreversibly inhibited the tip
      growth process. Thus the processes of tip growth and initiation of root hairs
      show differences in their pH requirements. These results highlight the role of
      localized control of apoplastic pH in the control of cell architecture and
      morphogenesis in plants.

PMID- 9655815
TI  - Leaf polarity and meristem formation in Arabidopsis.
AB  - Shoot apical meristems (SAMs) of seed plants are small groups of pluripotent
      cells responsible for making leaves, stems and flowers. While the primary SAM
      forms during embryogenesis, new SAMs, called axillary SAMs, develop later on the
      body of the plant and give rise to branches. In Arabidopsis plants, axillary SAMs
      develop in close association with the adaxial leaf base at the junction of the
      leaf and stem (the leaf axil). We describe the phenotype caused by the
      Arabidopsis phabulosa-1d (phb-1d) mutation. phb-1d is a dominant mutation that
      causes altered leaf polarity such that adaxial characters develop in place of
      abaxial leaf characters. The adaxialized leaves fail to develop leaf blades. This
      supports a recently proposed model in which the juxtaposition of ad- and abaxial
      cell fates is required for blade outgrowth. In addition to the alteration in leaf
      polarity, phb-1d mutants develop ectopic SAMs on the undersides of their leaves.
      Also, the phb-1d mutation weakly suppresses the shoot meristemless (stm) mutant
      phenotype. These observations indicate an important role for adaxial cell fate in
      promoting the development of axiallary SAMs and suggest a cyclical model for
      shoot development: SAMs make leaves which in turn are responsible for generating
      new SAMs.

PMID- 9655816
TI  - shaven and sparkling are mutations in separate enhancers of the Drosophila Pax2
      homolog.
AB  - We have previously shown that the sparkling gene, which like mammalian Pax2 plays
      an important role in eye development, is encoded by the Drosophila homolog of
      Pax2. Here we demonstrate that D-Pax2 also encodes the shaven function, which is
      crucial during bristle development. Both sv and spa alleles, previously thought
      to represent different genes, are mutations in two widely separated enhancers of
      D-Pax2. The sv function of D-Pax2 acts in at least two distinct steps of
      mechanosensory bristle development: the specification of the alternative fate of
      shaft as opposed to socket cell, and later the differentiation of the shaft cell.

PMID- 9655817
TI  - Interactions among Delta, Serrate and Fringe modulate Notch activity during
      Drosophila wing development.
AB  - The Notch signalling pathway plays an important role during the development of
      the wing primordium, especially of the wing blade and margin. In these processes,
      the activity of Notch is controlled by the activity of the dorsal specific
      nuclear protein Apterous, which regulates the expression of the Notch ligand,
      Serrate, and the Fringe signalling molecule. The other Notch ligand, Delta, also
      plays a role in the development and patterning of the wing. It has been proposed
      that Fringe modulates the ability of Serrate and Delta to signal through Notch
      and thereby restricts Notch signalling to the dorsoventral boundary of the
      developing wing blade. Here we report the results of experiments aimed at
      establishing the relationships between Fringe, Serrate and Delta during wing
      development. We find that Serrate is not required for the initiation of wing
      development but rather for the expansion and early patterning of the wing
      primordium. We provide evidence that, at the onset of wing development, Delta is
      under the control of apterous and might be the Notch ligand in this process. In
      addition, we find that Fringe function requires Su(H). Our results suggest that
      Notch signalling during wing development relies on careful balances between
      positive and dominant negative interactions between Notch ligands, some of which
      are mediated by Fringe.

PMID- 9655818
TI  - Neural crest emigration from the neural tube depends on regulated cadherin
      expression.
AB  - During the emergence of neural crest cells from the neural tube, the expression
      of cadherins dynamically changes. In the chicken embryo, the early neural tube
      expresses two cadherins, N-cadherin and cadherin-6B (cad6B), in the dorsal-most
      region where neural crest cells are generated. The expression of these two
      cadherins is, however, downregulated in the neural crest cells migrating from the
      neural tube; they instead begin expressing cadherin-7 (cad7). As an attempt to
      investigate the role of these changes in cadherin expression, we overexpressed
      various cadherin constructs, including N-cadherin, cad7, and a dominant negative
      N-cadherin (cN390 ), in neural crest-generating cells. This was achieved by
      injecting adenoviral expression vectors encoding these molecules into the lumen
      of the closing neural tube of chicken embryos at stage 14. In neural tubes
      injected with the viruses, efficient infection was observed at the neural crest
      forming area, resulting in the ectopic cadherin expression also in migrating
      neural crest cells. Notably, the distribution of neural crest cells with the
      ectopic cadherins changed depending on which constructs were expressed. Many
      crest cells failed to escape from the neural tube when N-cadherin or cad7 was
      overexpressed. Moreover, none of the cells with these ectopic cadherins migrated
      along the dorsolateral (melanocyte) pathway. When these samples were stained for
      Mitf, an early melanocyte marker, positive cells were found accumulated within
      the neural tube, suggesting that the failure of their migration was not due to
      differentiation defects. In contrast to these phenomena, cells expressing non
      functional cadherins exhibited a normal migration pattern. Thus, the
      overexpression of a neuroepithelial cadherin (N-cadherin) and a crest cadherin
      (cad7) resulted in the same blocking effect on neural crest segregation from
      neuroepithelial cells, especially for melanocyte precursors. These findings
      suggest that the regulation of cadherin expression or its activity at the neural
      crest-forming area plays a critical role in neural crest emigration from the
      neural tube.

PMID- 9655819
TI  - Overexpression of the forebrain-specific homeobox gene six3 induces rostral
      forebrain enlargement in zebrafish.
AB  - The Drosophila homeobox gene sine oculis is expressed in the rostral region of
      the embryo in early development and is essential for eye and brain formation. Its
      murine homolog, Six3, is expressed in the anterior neural plate and eye anlage,
      and may have crucial functions in eye and brain development. In this study, we
      describe the cloning and expression of zebrafish six3, the apparent ortholog of
      the mouse Six3 gene. Zebrafish six3 transcripts are first seen in hypoblast cells
      in early gastrula embryos and are found in the anterior axial mesendoderm through
      gastrulation. six3 expression in the head ectoderm begins at late gastrula.
      Throughout the segmentation period, six3 is expressed in the rostral region of
      the prospective forebrain. Overexpression of six3 in zebrafish embryos induced
      enlargement of the rostral forebrain, enhanced expression of pax2 in the optic
      stalk and led to a general disorganization of the brain. Disruption of either the
      Six domain or the homeodomain abolish these effects, implying that these domains
      are essential for six3 gene function. Our results suggest that the vertebrate
      Six3 genes are involved in the formation of the rostral forebrain.

PMID- 9655820
TI  - Sonic hedgehog is not required for the induction of medial floor plate cells in
      the zebrafish.
AB  - Sonic hedgehog (Shh) is a secreted protein that is involved in the organization
      and patterning of several tissues in vertebrates. We show that the zebrafish
      sonic-you (syu) gene, a member of a group of five genes required for somite
      patterning, is encoding Shh. Embryos mutant for a deletion of syu display defects
      in patterning of the somites, the lateral floor plate cells, the pectoral fins,
      the axons of motorneurons and the retinal ganglion cells. In contrast to mouse
      embryos lacking Shh activity, syu mutant embryos do form medial floor plate cells
      and motorneurons. Since ectopic overexpression of shh in zebrafish embryos does
      not induce ectopic medial floor plate cells, we conclude that shh is neither
      required nor sufficient to induce this cell type in the zebrafish.

PMID- 9655821
TI  - Cytoplasmic polyadenylation of Toll mRNA is required for dorsal-ventral
      patterning in Drosophila embryogenesis.
AB  - Toll encodes a receptor that is critical for dorsal-ventral patterning in the
      early Drosophila embryo. Previous data have suggested that the accumulation of
      Toll protein in the embryo temporally correlates with elongation of the poly (A)
      tail of the message. Here, we demonstrate that Toll mRNA is translationally
      activated by regulated cytoplasmic polyadenylation. We also identify a 192
      nucleotide regulatory element in the Toll 3' UTR that is necessary for robust
      translational activation of Toll mRNA and also regulates polyadenylation. UV
      crosslinking analyses suggest that two proteins bind specifically to the 192
      nucleotide element. One or both of these proteins may be factors that are
      required for translational regulation or cytoplasmic polyadenylation. These
      studies demonstrate that regulated polyadenylation plays a critical role in the
      Drosophila dorsal-ventral patterning system.

PMID- 9655823
TI  - Conformational changes on substrate binding to methylmalonyl CoA mutase and new
      insights into the free radical mechanism.
AB  - BACKGROUND: Methylmalonyl CoA mutase catalyses the interconversion of succinyl
      CoA and methylmalonyl CoA via a free radical mechanism. The enzyme belongs to a
      family of enzymes that catalyse intramolecular rearrangement reactions in which a
      group and a hydrogen atom on adjacent carbons are exchanged. These enzymes use
      the cofactor adenosylcobalamin (coenzyme B12) which breaks to form an adenosyl
      radical, thus initiating the reaction. Determination of the structure of
      substrate-free methylmalonyl CoA mutase was initiated to provide further insight
      into the mechanism of radical formation. RESULTS: We report here two structures
      of methylmalonyl CoA mutase from Propionibacterium shermanii. The first structure
      is of the enzyme in a nonproductive complex with CoA at 2.5 A resolution. This
      structure serves as a model for the substrate-free conformation of the enzyme, as
      it is very similar to the second much poorer 2.7 A resolution structure derived
      from a truly substrate-free crystal. The true substrate-free structure also shows
      the adenosyl group bound to the cobalt atom. Comparison of this structure with
      that of the previously reported complex of the enzyme with a substrate analogue
      shows that major conformational changes occur upon substrate binding. The
      substrate-binding site of the enzyme is located within a (beta alpha)8 TIM-barrel
      domain. In the absence of substrate, this TIM-barrel domain is split apart and
      the active site is accessible to solvent. When substrate binds, the barrel closes
      up with the substrate along its axis and the active site becomes completely
      buried. CONCLUSIONS: The closure of the active-site cavity upon substrate binding
      displaces the adenosyl group of the cofactor from the central cobalt atom into
      the active-site cavity. This triggers the formation of the free radical that
      initiates the rearrangement reaction. The TIM-barrel domain is substantially
      different from all others yet reported: in its unliganded form it is broken open,
      exposing the small hydrophilic sidechains which fill the centre. The typical
      barrel structure is only formed when substrate is bound.

PMID- 9655824
TI  - A mixed disulfide bond in bacterial glutathione transferase: functional and
      evolutionary implications.
AB  - BACKGROUND: Glutathione S-transferases (GSTs) are a multifunctional group of
      enzymes, widely distributed in aerobic organisms, that have a critical role in
      the cellular detoxification process. Unlike their mammalian counterparts,
      bacterial GSTs often catalyze quite specific reactions, suggesting that their
      roles in bacteria might be different. The GST from Proteus mirabilis (PmGST B1-1)
      is known to bind certain antibiotics tightly and reduce the antimicrobial
      activity of beta-lactam drugs. Hence, bacterial GSTs may play a part in bacterial
      resistance towards antibiotics and are the subject of intense interest. RESULTS:
      Here we present the structure of a bacterial GST, PmGST B1-1, which has been
      determined from two different crystal forms. The enzyme adopts the canonical GST
      fold although it shares less than 20% sequence identity with GSTs from higher
      organisms. The most surprising aspect of the structure is the observation that
      the substrate, glutathione, is covalently bound to Cys 10 of the enzyme. In
      addition, the highly structurally conserved N-terminal domain is found to have an
      additional beta strand. CONCLUSIONS: The crystal structure of PmGST B1-1 has
      highlighted the importance of a cysteine residue in the catalytic cycle. Sequence
      analyses suggest that a number of other GSTs share this property, leading us to
      propose a new class of GSTs - the beta class. The data suggest that the in vivo
      role of the beta class GSTs could be as metabolic or redox enzymes rather than
      conjugating enzymes. Compelling evidence is presented that the theta class of
      GSTs evolved from an ancestral member of the thioredoxin superfamily.

PMID- 9655825
TI  - Drug design against a shifting target: a structural basis for resistance to
      inhibitors in a variant of influenza virus neuraminidase.
AB  - BACKGROUND: Inhibitors of the influenza virus neuraminidase have been shown to be
      effective antiviral agents in humans. Several studies have reported the selection
      of novel influenza strains when the virus is cultured with neuraminidase
      inhibitors in vitro. These resistant viruses have mutations either in the
      neuraminidase or in the viral haemagglutinin. Inhibitors in which the glycerol
      sidechain at position 6 of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid
      (Neu5Ac2en) has been replaced by carboxamide-linked hydrophobic substituents have
      recently been reported and shown to select neuraminidase variants. This study
      seeks to clarify the structural and functional consequences of replacing the
      glycerol sidechain of the inhibitor with other chemical constituents. RESULTS:
      The neuraminidase variant Arg292-->Lys is modified in one of three arginine
      residues that encircle the carboxylate group of the substrate. The structure of
      this variant in complex with the carboxamide inhibitor used for its selection,
      and with other Neu5Ac2en analogues, is reported here at high resolution. The
      structural consequences of the mutation correlate with altered inhibitory
      activity of the compounds compared with wild-type neuraminidase. CONCLUSIONS: The
      Arg292-->Lys variant of influenza neuraminidase affects the binding of substrate
      by modification of the interaction with the substrate carboxylate. This may be
      one of the structural correlates of the reduced enzyme activity of the variant.
      Inhibitors that have replacements for the glycerol at position 6 are further
      affected in the Arg292-->Lys variant because of structural changes in the binding
      site that apparently raise the energy barrier for the conformational change in
      the enzyme required to accommodate such inhibitors. These results provide
      evidence that a general strategy for drug design when the target has a high
      mutation frequency is to design the inhibitor to be as closely related as
      possible to the natural ligands of the target.

PMID- 9655826
TI  - The structure of a methylated tetraloop in 16S ribosomal RNA.
AB  - BACKGROUND: Ribosomal RNAs contain many modified nucleotides. The functions of
      these nucleotides are poorly understood and few of them are strongly conserved.
      The final stem loop in 16S-like rRNAs is an exception in both regards. In both
      prokaryotes and eukaryotes, the tetranucleotide loop that caps the 3'-terminal
      stem contains two N6, N6-dimethyladenosine residues. The sequence and pattern of
      methylation are conserved within the loop, and there is evidence that these
      methylated nucleotides play an important role in subunit association and the
      initiation of protein synthesis. Because of the integral role that helix 45 plays
      in ribosome function, it is important to know what consequences these methylated
      nucleotides have on its structure. RESULTS: We have solved the solution structure
      of a 14-nucleotide analog of the terminal stem loop of bacterial 16S rRNA, which
      contains N2-methylguanosine as well as two N6,N6-dimethyladenosines. CONCLUSIONS:
      The methylation of the 16S rRNA stem loop completely alters its conformation,
      which would otherwise be a GNRA tetraloop. It is likely that the conformation of
      this loop is crucial for its function, having implications for its interaction
      with ribosomal subunits and its role in the initiation of protein synthesis.

PMID- 9655827
TI  - Crystal structures of reduced and oxidized DsbA: investigation of domain motion
      and thiolate stabilization.
AB  - BACKGROUND: The redox proteins that incorporate a thioredoxin fold have diverse
      properties and functions. The bacterial protein-folding factor DsbA is the most
      oxidizing of the thioredoxin family. DsbA catalyzes disulfide-bond formation
      during the folding of secreted proteins. The extremely oxidizing nature of DsbA
      has been proposed to result from either domain motion or stabilizing active-site
      interactions in the reduced form. In the domain motion model, hinge bending
      between the two domains of DsbA occurs as a result of redox-related
      conformational changes. RESULTS: We have determined the crystal structures of
      reduced and oxidized DsbA in the same crystal form and at the same pH (5.6). The
      crystal structure of a lower pH form of oxidized DsbA has also been determined
      (pH 5.0). These new crystal structures of DsbA, and the previously determined
      structure of oxidized DsbA at pH 6.5, provide the foundation for analysis of
      structural changes that occur upon reduction of the active-site disulfide bond.
      CONCLUSIONS: The structures of reduced and oxidized DsbA reveal that hinge
      bending motions do occur between the two domains. These motions are independent
      of redox state, however, and therefore do not contribute to the energetic
      differences between the two redox states. Instead, the observed domain motion is
      proposed to be a consequence of substrate binding. Furthermore, DsbA's highly
      oxidizing nature is a result of hydrogen bond, electrostatic and helix-dipole
      interactions that favour the thiolate over the disulfide at the active site.

PMID- 9655828
TI  - Validation tools: can they indicate the information content of macromolecular
      crystal structures?
AB  - The explosive increase in the number of published three-dimensionsal structures
      of macromolecules determined by X-ray analysis places a responsibility on
      experimentalists, referees and curators of databases to ensure correspondence
      between the structure parameters and data. Validation tools will evolve as more
      appropriate statistical techniques and new information, such as that from
      proteins analysed at atomic resolution, becomes available.

PMID- 9655829
TI  - Mapping protein-ligand interactions by footprinting, a radical idea.

PMID- 9655830
TI  - Lactate dehydrogenase from the hyperthermophilic bacterium thermotoga maritima:
      the crystal structure at 2.1 A resolution reveals strategies for intrinsic
      protein stabilization.
AB  - BACKGROUND: L(+)-Lactate dehydrogenase (LDH) catalyzes the last step in anaerobic
      glycolysis, the conversion of pyruvate to lactate, with the concomitant oxidation
      of NADH. Extensive physicochemical and structural investigations of LDHs from
      both mesophilic and thermophilic organisms have been undertaken in order to study
      the temperature adaptation of proteins. In this study we aimed to determine the
      high-resolution structure of LDH from the hyperthermophilic bacterium Thermotoga
      maritima (TmLDH), the most thermostable LDH to be isolated so far. It was hoped
      that the structure of TmLDH would serve as a model system to reveal strategies of
      protein stabilization at temperatures near the boiling point of water. RESULTS:
      The crystal structure of the extremely thermostable TmLDH has been determined at
      2.1 A resolution as a quaternary complex with the cofactor NADH, the allosteric
      activator fructose-1,6-bisphosphate, and the substrate analog oxamate. The
      structure of TmLDH was solved by Patterson search methods using a homology-based
      model as a search probe. The native tetramer shows perfect 222 symmetry.
      Structural comparisons with five LDHs from mesophilic and moderately thermophilic
      organisms and with other ultrastable enzymes from T. maritima reveal possible
      strategies of protein thermostabilization. CONCLUSIONS: Structural analysis of
      TmLDH and comparison of the enzyme to moderately thermophilic and mesophilic
      homologs reveals a strong conservation of both the three-dimensional fold and the
      catalytic mechanism. Going from lower to higher physiological temperatures a
      variety of structural differences can be observed: an increased number of
      intrasubunit ion pairs; a decrease of the ratio of hydrophobic to charged surface
      area, mainly caused by an increased number of arginine and glutamate sidechains
      on the protein surface; an increased secondary structure content including an
      additional unique 'thermohelix' (alphaT) in TmLDH; more tightly bound
      intersubunit contacts mainly based on hydrophobic interactions; and a decrease in
      both the number and the total volume of internal cavities. Similar strategies for
      thermal adaptation can be observed in other enzymes from T. maritima.

PMID- 9655831
TI  - The structure and function of antiamoebin I, a proline-rich membrane-active
      polypeptide.
AB  - BACKGROUND: Antiamoebin is a member of the peptaibol family of polypeptides and
      has a unique antibiotic activity: it acts as an antiamoebic agent, but does not
      effectively haemolyze erythrocytes even though it does exhibit membrane-modifying
      activity. RESULTS: The structure of antiamoebin I has been determined by X-ray
      crystallography at 1.4 A resolution. The molecule forms a helical structure,
      which, as a result of the presence of a number of proline and hydroxyproline
      residues, has a deep bend in the middle. Circular dichroism spectroscopy, single
      channel conductance studies and fluorescence diffusion studies suggest a mode of
      ion transport that is entirely different from that of the other two members of
      the peptaibol family (alamethicin and zervamicin) whose structures and functions
      have been examined in detail. CONCLUSIONS: The structure of the polypeptide has
      been determined and a functional model for its mode of action in membranes is
      presented. Although under some conditions antiamoebin may form ion channels,
      unlike the closely related alamethicin and zervamicin polypeptides, its major
      membrane-modifying activity appears to be as an ion carrier.

PMID- 9655832
TI  - The structure of immunoglobulin superfamily domains 1 and 2 of MAdCAM-1 reveals
      novel features important for integrin recognition.
AB  - BACKGROUND: Mucosal addressin cell adhesion molecule 1 (MAdCAM-1) is a cell
      adhesion molecule that is expressed on the endothelium in mucosa, and guides the
      specific homing of lymphocytes into mucosal tissues. MAdCAM-1 belongs to a
      subclass of the immunoglobulin superfamily (IgSF), the members of which are
      ligands for integrins. Human MAdCAM-1 has a unique dual function compared to
      other members in the same subclass in that it binds both the integrin
      alpha4beta7, through its two IgSF domains, and a selectin expressed on
      leukocytes, via carbohydrate sidechains. The structure determination of the two
      IgSF domains and comparison to the N-terminal two-domain structures of vascular
      cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecules (ICAM-1
      and ICAM-2) allow us to assess the molecular basis of the interactions between
      integrins and their preferred ligands. RESULTS: The crystal structure of a
      fragment containing the two IgSF domains of human MAdCAM-1 has been determined to
      2.2 A resolution. The structure of MAdCAM-1 reveals two separate integrin
      recognition motifs. The key integrin-binding residue, Asp42, resides in the CD
      loop of domain 1; a buried arginine residue (Arg70) plays a critical role in
      maintaining the conformation of this loop. The second binding site is associated
      with an unusual long D strand in domain 2. The D and E strands extend beyond the
      main body of the domain, forming a negatively charged beta ribbon unique to
      MAdCAM-1. This ribbon is located on the same face as the key aspartate residue in
      domain 1, consistent with evidence that it is involved in integrin binding.
      CONCLUSIONS: The structural comparison of MAdCAM-1 to other members of the same
      IgSF subclass reveals some interesting features. Firstly, MAdCAM-1, like VCAM-1,
      has the key integrin-binding residue located on the protruding CD loop of domain
      1 and binds to an integrin that lacks an I domain. This is in contrast to ICAM-1
      and ICAM-2 where the key residue is located at the end of the C strand on a flat
      surface and which bind to integrins that contain I domains. Secondly,
      architectural differences in the CD loops of MAdCAM-1 and VCAM-1 cause an 8 A
      shift in position of the critical aspartate residue, and may partly determine
      their binding preference for different integrins. Finally, the unusual charge
      distribution of the two-domain fragment of MAdCAM-1 is predicted to orient the
      molecule optimally for integrin binding on the top of its long mucin-like stalk.

PMID- 9655833
TI  - Functional universality and evolutionary diversity: insights from the structure
      of the ribosome.
AB  - The structure of the mammalian ribosome, reconstructed at 25 A resolution, has
      added a new dimension to our current knowledge, as it manifests the conservation
      and universality of the ribosome in respect to its primary tasks in protein
      biosynthesis. A combined approach to study of the ribosome, using X-ray
      crystallography and electron microscopy, may further improve our understanding of
      ribosome function in the future.

PMID- 9655835
TI  - Mechanisms of lysophosphatidylcholine-induced increase in intracellular calcium
      in rat cardiomyocytes.
AB  - Previous reports have demonstrated that lysophosphatidylcholine (LPC) increases
      the intracellular concentration of calcium ([Ca++]i) in the heart; however, the
      mechanisms responsible for this increase are not clear. We examined the effect of
      exogenous LPC on [Ca++]i in freshly isolated cardiomyocytes from adult rats. Our
      results showed that LPC elevated the [Ca++]i in a dose-dependent (2.5-10 microM)
      manner. The LPC (10 microM)-induced increase in [Ca++]i was augmented upon
      increasing the concentration of extracellular Ca++ and was abolished by the
      removal of Ca++ from the medium. Preincubation of cardiomyocytes with sarcolemmal
      L-type Ca++ channel blocker, verapamil, did not affect the LPC-evoked increase in
      [Ca++]i significantly. On the other hand, ouabain, a Na(+)-K+ ATPase inhibitor,
      and low concentrations of extracellular Na+ enhanced the LPC response. The LPC
      induced increase in [Ca++]i was attenuated significantly by the inhibitors of
      Na(+)-Ca++ exchanger such as Ni++ and amiloride. Depletion of the sarcoplasmic
      reticulum (SR) Ca++ stores by low micromolar concentrations of ryanodine (a SR
      Ca(++)-release channel activator) or by thapsigargin (a SR Ca(++)-pump ATPase
      inhibitor) depressed the LPC-mediated increase in [Ca++]i. Combined blockade of
      Na(+)-Ca++ exchanger and inhibition of SR Ca(++)-pump or ryanodine receptor had
      an additive effect on the LPC response. These observations suggest that the
      increase in [Ca++]i induced by LPC depends on both Ca(++)-influx from the
      extracellular space and Ca(++)-release from the SR stores. Furthermore, Na(+)
      Ca++ exchange plays a critical role in the LPC-mediated entry of Ca++ into
      cardiomyocytes.

PMID- 9655836
TI  - Ionic mechanism of ibutilide in human atrium: evidence for a drug-induced Na+
      current through a nifedipine inhibited inward channel.
AB  - This study examined the ionic mechanism of ibutilide, a class III antiarrhythmic
      in clinical use, on freshly isolated human atrial cells. Cells had resting
      potentials of -71.4 +/- 2.4 mV, action potentials with overshoot of 36.8 +/- 1.8
      mV, duration of 265 +/- 89 msec at 90% repolarization and slow repolarization (n
      = 16). Ibutilide, at 10(-7) M, markedly increased action potential duration. Four
      types of outward currents were detected: Ito, Iso, a delayed rectifier and IK1.
      Ibutilide had no inhibitory effect on these outward currents at 10(-7) M (n =
      28). In K(+)-free solutions and -40 mV holding potential, mean peak inward
      current at 20 mV was -1478 +/- 103 pA (n = 12). Ibutilide increased this current
      to -2347 +/- 75 pA at 10(-7) M, with half maximal effect (Kd) of 0.1 to 0.9 nM
      between -10 and +40 mV (n = 21). At similar concentrations, the drug increased
      APD, with Kd of 0.7 and 0.23 nM at 70 and 90% repolarization, respectively (n =
      8). Ibutilide shifted the mid-point of the steady-state inactivation curve from 
      21 to -12.2 mV (n = 6), and reduced current decline during repetitive
      depolarization (n = 5). The drug induced inward current was carried by Na+o
      through a nifedipine inhibited inward channel because Na+o removal eliminated the
      effect, and nifedipine abolished the inward current and the drug induced APD
      prolongation. We propose that a Na+ current through the L-type Ca++ channel
      mediates ibutilide's potent clinical class III antiarrhythmic action.

PMID- 9655837
TI  - Trimetazidine counteracts the hepatic injury associated with ischemia-reperfusion
      by preserving mitochondrial function.
AB  - Recent studies suggest a crucial role played by mitochondria in the pathogenesis
      of ischemia-reperfusion injury. This study was conducted to clarify the role of
      trimetazidine, a cellular anti-ischemic agent, on mitochondria isolated from rat
      liver subjected to 120-min normothermic ischemia followed by 30-min reperfusion.
      Rats were divided into groups, pretreated with different doses of trimetazidine
      (5, 10 and 20 mg/kg/day) or saline and subjected to the ischemia-reperfusion
      process; another group served as the sham-operated controls. Alanine
      aminotransferase and aspartate aminotransferase activities and hepatocyte ATP
      content, bile flow and mitochondrial functions were assessed. Ischemia
      reperfusion caused membrane leakage from hepatocytes and a decrease in ATP
      content and in bile flow. These effects were well correlated with alterations in
      mitochondrial function, namely, decrease in ATP synthesis, NAD(P)H level and
      mitochondrial membrane potential and generation of mitochondrial permeability
      transition. The pretreatment of rats with trimetazidine prevented these ischemia
      reperfusion deleterious effects at both the cellular and mitochondrial level in a
      dose-dependent manner. It is concluded that trimetazidine at an optimal dosage of
      10 mg/kg/day protects mitochondria against the deleterious effects of ischemia
      reperfusion. This protective effect appears to be the key factor through which
      this drug exerts its cytoprotective activity.

PMID- 9655838
TI  - Pharmacodynamic activities of ciprofloxacin and sparfloxacin in a murine
      pneumococcal pneumonia model: relevance for drug efficacy.
AB  - We looked for associations between pharmacokinetic (Pk) and pharmacodynamic (Pd)
      parameters of ciprofloxacin (CPFX) and sparfloxacin (SPFX) and the in vivo
      efficacy of these antimicrobials in an immunocompetent mouse model of severe
      Streptococcus pneumoniae pneumonia. Bacterial killing curves recorded in the
      lungs during the 24 h after single subcutaneous injections of the
      fluoroquinolones (FQs) in doses ranging from 6.25 to 200 mg/kg were compared with
      mean Pk/Pd parameters in the serum of the same mice. The impact of the dosing
      interval on the antimicrobial dose response was evaluated based on the survival
      of mice treated for 3 days with CPFX (25-200 mg/kg) or SPFX (6.25-50 mg/kg)
      administered at various intervals from 3 to 24 h. Bacterial killing curves showed
      that the maximal bacterial decrease achieved in the lungs was correlated,
      similarly for both FQs, with the area under the curve (AUC) above the minimal
      inhibitory concentration (MIC) (overall correlation: r = 0.968, P < 10(-4)). CPX
      attained higher maximal bactericidal effect values, a steeper killing slope and a
      shorter time to maximal bactericidal effect in comparison with SPX for the
      highest doses tested. The lower MIC of SPFX compared with CPFX (0.25 vs. 0.75
      microgram/ml) and its higher AUC/dose ratio (resulting from a lower serum peak
      but a longer half-life) translated into a greater area under the bactericidal
      curve. In the dose fractionation experiments, the Pk/Pd parameter most closely
      correlated with the survival rate for both FQs was the daily AUC/MIC ratio (r =
      0.976, P < 10(-4)). When the AUC/MIC ratio was greater than 160, the probability
      of a clinical cure was 100%, independently of the dosage schedule.

PMID- 9655840
TI  - Involvement of dopaminergic system in phencyclidine-induced place preference in
      mice pretreated with phencyclidine repeatedly.
AB  - In the conditioned place preference test, phencyclidine (PCP) produces place
      aversion in naive rats, whereas PCP produces place preference in rats treated
      with PCP repeatedly. Although the PCP-induced place aversion is thought to
      involve the serotonergic system, the mechanisms of the PCP-induced place
      preference are unclear. We investigated whether the dopaminergic system is
      involved in place preference induced by PCP in mice repeatedly treated with PCP,
      because it is well known that the dopaminergic system plays an important role in
      the rewarding effect of drugs. PCP (2-8 mg/kg s.c.) induced a dose-dependent
      place aversion in naive mice, whereas PCP (2-8 mg/kg s.c.) induced a dose
      dependent place preference in mice pretreated with PCP (10 mg/kg/day s.c.) for 28
      days. The place preference induced by PCP (8 mg/kg s.c.) was attenuated
      significantly by alpha-methyl-rho-tyrosine (100 mg/kg i.p.), a tyrosine
      hydroxylase inhibitor, 6-hydroxydopamine (100 micrograms/mouse i.c.v.), a
      dopaminergic neurotoxin, and R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5
      tetrahydro-1H-3-benza zepine (0.5 mg/kg s.c.), a dopamine D1 receptor antagonist.
      These agents themselves produced neither the place preference nor aversion. In
      contrast to the attenuating effects of these agents, N-(2-chloroethyl)-N-ethyl-2
      bromobenzylamine (30 mg/kg i.p.), a noradrenergic neurotoxin, ritanserin (1 mg/kg
      i.p.), a serotonin2 receptor antagonist, and (-) sulpiride (50 and 100 mg/kg
      i.p.), a dopamine D2 receptor antagonist, failed to affect the PCP-induced place
      preference. In mice pretreated with methamphetamine (1 mg/kg/day s.c.) for 14
      days, PCP (8 mg/kg s.c.) induced the place preference, but not aversion. These
      results demonstrate that the PCP-induced place preference depends on
      dopaminergic, but not on serotonergic and noradrenergic, neuronal systems and
      suggest a role for D1 receptors in the mediation of the PCP-induced place
      preference.

PMID- 9655839
TI  - Protein kinase C does not mediate phenylephrine-induced down-regulation of Madin
      Darby canine kidney cell alpha-1B adrenoceptors.
AB  - We examined the down-regulation of alpha-1B adrenoceptors in Madin-Darby canine
      kidney D1 (MDCK) cells with an emphasis on a possible role of protein kinase C.
      The alpha-1 adrenoceptor agonist phenylephrine (1-100 microM) concentration
      dependently down-regulated alpha-1B adrenoceptors in MDCK cells. Down-regulation
      by 100 microM phenylephrine was detectable after 2 hr and maximal after 8 to 24
      hr. The receptor down-regulation was accompanied by a decrease in phenylephrine
      stimulated inositol phosphate formation but not by an altered expression of
      immunodetectable Gq/11 alpha subunits. Even though alpha-1B adrenoceptor and P2
      purinergic receptor stimulation promote prostaglandin E2 formation, receptor down
      regulation was not prevented by indomethacin (10 microM) treatment but was partly
      mimicked by treatment with the purinergic receptor agonists adenosine-5'-O-(3
      thio)triphosphate and 2-methylthio-ATP (300 microM each). Phorbol-12-myristate-13
      acetate (1-100 nM) concentration-dependently down-regulated MDCK alpha-1B
      adrenoceptors to a greater extent than did phenylephrine. Three protein kinase C
      inhibitors, H7 (100 microM), staurosporine (100 nM) and KT5926 (1 microM),
      markedly attenuated receptor down-regulation promoted by phorbol ester but did
      not affect that by phenylephrine. Two inhibitors of Ca++/calmodulin protein
      kinase pathways, KT5926 (1 microM) and W-7 (30 microM), also failed to prevent
      phenylephrine-induced down-regulation of alpha-1B adrenoceptors. We conclude that
      agonist-induced down-regulation of MDCK cell alpha-1B adrenoceptors is mimicked
      by a protein kinase C-activating phorbol ester but that the second messenger
      kinases protein kinase C and Ca++/calmodulin protein kinase do not mediate
      agonist-induced down-regulation of the alpha-1B adrenoceptor.

PMID- 9655841
TI  - Relation of cysteine conjugate nephrotoxicity to transport by the basolateral
      organic anion transport system in isolated S2 segments of rabbit proximal renal
      tubules.
AB  - We examined basolateral transport of the radiolabeled zwitterionic nephrotoxic
      cysteine S-conjugate, S-(1,2-dichlorovinyl)-L-cysteine (DCVC), inhibition of such
      transport and the effects of inhibition of transport on the toxicity produced by
      DCVC in isolated S2 segments of rabbit proximal tubules. High concentrations of
      unlabeled DCVC itself and an unlabeled nontoxic cysteine S-conjugate, S-(2
      benzothiazole)-L-cysteine cis-inhibited the basolateral uptake of radiolabeled
      DCVC by approximately 80 to 85%. High concentrations of para-aminohippurate, the
      prototype substrate for the basolateral organic anion transport system, and
      probenecid, a well-known inhibitor of basolateral organic anion transport, cis
      inhibited the basolateral uptake of radiolabeled DCVC by approximately 70%,
      whereas a high concentration of L-phenylalanine had little effect. High
      concentrations of S-(2-benzothiazole)-L-cysteine and para-aminohippurate in the
      bathing medium with DCVC inhibited the loss of 86Rb (used as a K+ surrogate to
      measure toxicity) from S2 segments produced by DCVC alone to approximately the
      same extent as they inhibited uptake of DCVC. Under the same circumstances,
      probenecid completely inhibited 86Rb loss. These data indicate that in rabbit
      proximal renal S2 tubules basolateral entry of DCVC can occur to a major extent
      via the organic anion transport pathway and that inhibition of such entry can
      reduce toxicity to approximately the same extent that entry is reduced. They also
      suggest that probenecid provides additional protection from DCVC toxicity.

PMID- 9655842
TI  - Self-administration of cocaine-heroin combinations by rhesus monkeys: antagonism
      by naltrexone.
AB  - Low, nonreinforcing doses of heroin have been shown to shift the dose-response
      function of cocaine leftward in rhesus monkeys trained under a progressive-ratio
      schedule of i.v. drug injection. Our study sought to determine 1) whether a
      reciprocal enhancement of heroin self-administration would be observed when
      heroin was combined with low, nonreinforcing doses of cocaine, and 2) whether
      self-administration of cocaine-heroin combinations could be antagonized by the
      opioid antagonist naltrexone. Rhesus monkeys (n = 4) were prepared with i.v.
      catheters and trained to self-administer cocaine under a progressive-ratio
      schedule. The initial response requirement of this schedule was fixed-ratio 120,
      which doubled across the session to a maximum of 1920. Injections were separated
      by a 30-min time out. Cocaine dose-response functions (6.4-100
      micrograms/kg/injection) for injections/session and breakpoints were monophasic,
      i.e., increased with dose until responding reached a maximum. Heroin dose
      response functions (1.6-25 micrograms/kg/ injection) either increased to a peak
      and then decreased or reached an asymptote. When nonreinforcing doses of cocaine
      (3.2-25 micrograms/kg/injection) were combined with heroin, the heroin dose
      response function was shifted to the left, without change in maximum
      injections/session. Pressession treatments with naltrexone (3.2-1600
      micrograms/kg, i.m., 10-min presession) antagonized self-administration of heroin
      and heroin + cocaine combinations in a dose-dependent fashion. However,
      naltrexone treatment had no effect on cocaine self-administration. Antagonism by
      naltrexone of self-administration of heroin and heroin + cocaine was surmounted
      by increasing the dose of heroin either alone or in the heroin + cocaine
      combination. In vivo apparent pA2 and pKB analyses of these data revealed values
      of approximately 8.0, consistent with a role for mu opioid receptors in the self
      administration of heroin and cocaine-heroin (i.e., "speedball") combinations.

PMID- 9655843
TI  - C-type natriuretic peptide increases myocardial contractility and sinus rate
      mediated by guanylyl cyclase-linked natriuretic peptide receptors in isolated,
      blood-perfused dog heart preparations.
AB  - There are no available data on the direct effect of C-type natriuretic peptide
      (CNP) and brain natriuretic peptide (BNP) on the myocardial contractility in
      mammalian hearts. Thus we studied the inotropic and chronotropic effects of CNP
      22 and BNP-32 compared with those of atrial natriuretic peptide (ANP)-28 using
      the isolated, blood-perfused canine right atrial or left ventricular
      preparations. CNP increased the atrial contractile force in a dose-dependent
      manner with a small increase in sinus rate in isolated atria, whereas neither ANP
      nor BNP changed atrial force and rate. CNP but not BNP also increased the
      ventricular contractile force in isolated ventricles. Pretreatment with a high
      dose (3 nmol) of CNP attenuated the positive inotropic response to CNP at a low
      dose (1 nmol) but not to norepinephrine. A guanylyl cyclase-linked natriuretic
      peptide receptor antagonist, HS-142-1, inhibited the increases in atrial
      contractile force and sinus rate in response to CNP, but it did not affect the
      positive cardiac responses to norepinephrine. Propranolol did not block the
      positive cardiac responses to CNP. 3-Isobutyl-1-methylxanthine in rates of 0.6 to
      1.3 mumol/ min attenuated the CNP-induced positive inotropic responses, when it
      potentiated the positive inotropic response to norepinephrine. On the other hand,
      parasympathetic nerve stimulation attenuated the positive cardiac responses to
      CNP and norepinephrine. These results demonstrate that CNP increases myocardial
      contractile force with a small increase in sinus rate mediated by guanylyl
      cyclase-linked natriuretic peptide receptors, probably type B receptors in the
      dog heart, and suggest that the positive inotropic response to CNP is influenced
      by the cyclic adenosine 3',5'-monophosphate-dependent signal transduction.

PMID- 9655844
TI  - First evidence of otoprotection against carboplatin-induced hearing loss with a
      two-compartment system in patients with central nervous system malignancy using
      sodium thiosulfate.
AB  - Sodium thiosulfate (STS) provides protection against carboplatin-induced
      ototoxicity in an animal model. The purpose of this study was to determine the
      STS dose required for otoprotection, in patients with malignant brain tumors
      treated with carboplatin in conjunction with osmotic blood-brain barrier
      disruption. Twenty-nine patients received STS intravenously 2 hr after
      carboplatin. Doses were escalated from 4 g/m2 to 8, 12, 16 and 20 g/m2 on
      consecutive months. Audiologic assessment was performed at baseline and monthly.
      The audiograms were compared with those of 19 similarly treated historical
      control patients who did not receive STS. The incidence of ototoxicity in the
      historical control group of patients was 79% (15/19). This group had an average
      loss of 20.8 +/- 5.9 dB (n = 19) at 8 kHz after one treatment with carboplatin,
      whereas the STS treatment group lost only 3.7 +/- 2 dB (n = 15) after one
      treatment. This difference was statistically significant as assessed by Student's
      t test (P < .05). Furthermore, patients in the STS treatment group with excellent
      base-line hearing showed little change in hearing thresholds at 8 kHz after the
      second treatment (8.0 +/- 8.3 dB) (n = 5) compared with the historical control
      patients with excellent base-line hearing, (40.5 +/- 8.6 dB) (n = 11). Our data
      support that doses of 16 or 20 g/m2 of STS decrease carboplatin-induced hearing
      loss without central nervous system entry. Clinical demonstration of an
      otoprotective effect with a two-compartment system to prevent drug-induced
      hearing loss, while preserving central nervous system cytotoxicity, has not been
      reported previously.

PMID- 9655845
TI  - Creation of a constitutively activated state of the 5-hydroxytryptamine2A
      receptor by site-directed mutagenesis: inverse agonist activity of antipsychotic
      drugs.
AB  - Single amino acid mutations in the third intracellular loop, as well as other
      domains of G protein-coupled receptors, have been shown to confer drastic changes
      in receptor properties and have been postulated to be responsible for various
      disease states. To determine whether an amino acid mutation can confer dramatic
      alterations in the 5-hydroxytryptamine2A (5-HT2A) receptor, we mutated amino acid
      322 to lysine (C322K), glutamate (C322E) or arginine (C322R). Transient
      expression of the mutant receptors revealed properties associated with
      constitutive activity. Radioligand binding studies revealed an increase in 5-HT
      affinity from 293 nM (native) to 86 nM (C322E), 25 nM (C322K) and 11 nM (C322R).
      5-HT potency for stimulation of inositol phosphate production increased from 152
      nM (native) to 61 nM (C322E) and 25 nM (C322K). Basal inositol phosphate levels
      in COS-7 cells expressing C322K and C322E mutant receptors were 8-fold and 4-fold
      higher, respectively, than cells expressing native 5-HT2A receptors. Basal levels
      of inositol phosphate stimulated by C322K receptors represented 48% of total
      inositol phosphate production stimulated by native receptors in the presence of
      10 microM 5-HT. Antipsychotic drugs (chlorpromazine, clozapine, haloperidol,
      loxapine and risperidone) displayed inverse agonist activity by inhibiting C322K
      constitutive activation of phosphatidylinositol hydrolysis. These data indicate
      that amino acid 322 in the 5-HT2A receptor plays an important role in maintaining
      the inactive conformation and provide further evidence that amino acid mutations
      can produce profound alterations in G protein-coupled receptor activity.

PMID- 9655846
TI  - Muscarinic receptors regulate extracellular glutamate levels in the rat striatum:
      an in vivo microdialysis study.
AB  - Regulation of extracellular glutamate levels by muscarinic receptors in the
      striatum of unanesthetized rats was investigated by microdialysis. Extracellular
      glutamate levels were elevated by intrastriatal perfusion of L-trans-pyrrolidine
      2,4-dicarboxylic acid (L-trans-PDC), a competitive substrate of plasma membrane
      excitatory amino acid transporters. The nonselective muscarinic agonist,
      oxotremorine (0.5-54 microM) significantly decreased L-trans-PDC-evoked glutamate
      levels in a concentration-dependent manner. Scopolamine (0.1-10 microM), a
      nonselective muscarinic receptor antagonist, reversed the effect of oxotremorine,
      which confirms that muscarinic receptor activation mediated the reduction of L
      trans-PDC-evoked glutamate levels. In addition, scopolamine (10 microM)
      significantly elevated basal extracellular glutamate levels, an effect prevented
      by oxotremorine, which suggests that acetylcholine tonically regulates
      glutamatergic transmission in the striatum. Previous data from this laboratory
      have shown that L-trans-PDC-evoked glutamate levels are partially calcium
      dependent. The present study demonstrated that attenuation of L-trans-PDC-evoked
      glutamate levels by reduced calcium was not altered by oxotremorine. Therefore,
      it is likely that muscarinic receptors regulate calcium-dependent glutamate
      release evoked by L-trans-PDC.

PMID- 9655847
TI  - Extracellular 3',5' cyclic guanosine monophosphate inhibits kainate-activated
      responses in cultured mouse cerebellar neurons.
AB  - The effects of extracellularly applied 3'-5' cyclic guanosine monophosphate
      (cGMP) on kainate responses from cultured cerebellar granule and Purkinje neurons
      were investigated using whole-cell and outside-out patch recording modes.
      Cerebellar granule cell responses to kainate were not homogeneous, nor were the
      effects of cGMP. Therefore, effects of cGMP are described for two groups of
      granule cells categorized on the basis of the underlying channel conductance
      estimated by variance analysis. Cells with high-noise kainate responses had
      average channel conductances of 5 to 7 picoseimens, whereas the average
      conductances of low-variance noise responses were 0.3 to 2.0 picoseimens. High
      noise kainate responses were inhibited by externally applied cGMP (5-1000 microM)
      in a rapidly reversible and dose-dependent manner. IC50 values were estimated at
      approximately 150 microM cGMP for 25 microM kainate and approximately 500 microM
      cGMP for 100 microM kainate. Evidence that cGMP-mediated inhibition of high-noise
      kainate responses occurred by a competitive mechanism included the following: 1)
      cGMP-mediated inhibition was overcome by increasing agonist concentration. 2) The
      shape of kainate current-voltage (I-V) curves and their reversal potentials were
      unchanged in cGMP. 3) Neither the estimated conductance nor the kinetics of the
      kainate-activated channels was affected by cGMP. In contrast to the uniform
      effects of cGMP on the high-noise kainate responses, the effects on low-noise
      kainate responses were variable. Half of the low-noise kainate responses were
      inhibited by cGMP to a similar extent as the high-noise responses; however, the
      other 50% of cells exhibiting low-noise kainate responses appeared to be less
      sensitive to the cyclic nucleotide. Moreover, cGMP coapplication decreased the
      estimated conductances for some low-noise kainate responses and altered their
      noise kinetics, which suggests either that cGMP-sensitive and -insensitive
      kainate receptor channels are coexpressed in these cells or that cGMP-mediated
      inhibition is not competitive for this subgroup of glutamate receptor channels.
      Overall, these data indicate that there are direct inhibitory effects of
      extracellular cGMP on a large group of excitatory synapses in the CNS--effects
      that need to be taken into account when investigators utilize membrane-permeable
      cGMP analogs. Whether this cGMP-mediated inhibition has a functional role in
      brain is unknown.

PMID- 9655848
TI  - Relaxing effects of NO donors on guinea pig trachea in vitro are mediated by
      calcium-sensitive potassium channels.
AB  - The relaxing effects of the nitric oxide (NO) donors 1,2,3,4-oxatriazolium,3-(3
      chloro-2-methylphenyl-5-[[(4-methoxyphe nyl) sulfonyl]amino]-,hydroxide inner
      salt (GEA 3268) 1,2,3,4-oxatriazolium,3-(3-chloro-2-methyphenyl-5-[methys
      ulfonyl)amino]- hydroxide inner salt (GEA 5145), 3-morpholinosydnonimine (SIN-1)
      and S-nitroso-N-acetylpenicillamine (SNAP) were inhibited in vitro by iberiotoxin
      (IbTX) and charybdotoxin (ChTX), the two selective inhibitors of Ca(++)-activated
      K+ channels (KCa) in guinea pig trachea. When studied in cumulative
      concentrations in metacholine constriction, the relaxing effects of the NO donors
      were inhibited by at least 70% in the presence of the toxins, with the exception
      of SIN-1 in the presence of ChTX. The inhibitory effect of ChTX was less marked
      than that of IbTX. This suggests that the relaxing effects of the structurally
      different NO donors are mediated through KCa channels and that IbTX is more
      potent than ChTX. A selective inhibitor of soluble guanylate cyclase, 1H
      [1,2,4]oxadiazolo[4,3-a]quinozalin-1-one (ODQ), significantly inhibited the
      relaxing effects of GEA 3268 and GEA 5145 on metacholine and KCl constriction and
      almost totally inhibited the relaxing effects of SIN-1 and SNAP. The inhibitor of
      the delayed rectifier K+ channel current 4-aminopyridine did not influence the
      relaxations of the NO donors, and under the experimental conditions of this
      study, the ATP-sensitive K+ channel inhibitor glibenclamide had no effect. In
      conclusion, the relaxing effects of the structurally different NO-releasing
      compounds are mediated via KCa channels. However, the significance of some other
      possible mechanisms unrelated to K+ channels cannot be excluded.

PMID- 9655849
TI  - Effect of nitric oxide-releasing aspirin derivative on gastric functional and
      ulcerogenic responses in rats: comparison with plain aspirin.
AB  - The effects of a nitric oxide (NO)-releasing derivative of aspirin, NCX-4016, on
      gastric functional and ulcerogenic responses in rat stomachs were examined in
      comparison with those of aspirin. Topical application of aspirin (80 mM) to the
      stomach markedly decreased transmucosal potential difference and slightly
      increased luminal pH (acid back-diffusion) with minimal effect on mucosal blood
      flow, whereas NCX-4016 caused a marked increase in mucosal blood flow with no
      effect on potential difference and pH. Aspirin itself was ulcerogenic, causing
      damage in the mucosa when administered p.o., and it markedly potentiated gastric
      ulcerogenic response to hypothermic stress (28 degrees C-30 degrees C) with no
      effect on acid secretion when given s.c. NCX-4016, however, was not ulcerogenic
      by itself, did not modify the ulcerogenic response to stress and even showed a
      dose-dependent protection against HCl/ethanol-induced gastric lesions. When NCX
      4016 was given intragastrically to pylorus-ligated rats, a large amount of NO was
      detected in both gastric contents and serum. NCX-4016 administered either p.o. or
      s.c. produced an equipotent inhibition of mucosal PGE2 generation in the stomach,
      as compared with aspirin. In addition, both aspirin and NCX-4016 suppressed
      carrageenan-induced rat paw edema. These results suggest that, unlike aspirin,
      the NO-releasing derivative of aspirin NCX-4016 neither had a topical irritating
      action on the stomach nor exerted a worsening effect on gastric ulcerogenic
      response to stress, but rather provided gastric protection against ethanol,
      despite inhibiting cyclo-oxygenase activity and showing anti-inflammatory action
      much as aspirin does. NCX-4016, probably by releasing NO, exerted protective
      effects that counteracted the potential damaging effects of cyclo-oxygenase
      inhibition.

PMID- 9655850
TI  - Prediction of in vivo nonlinear first-pass hepatic metabolism of YM796 from in
      vitro metabolic data.
AB  - Recent cumulative evidence suggests the possibility of predicting the in vivo
      metabolic clearance and/or hepatic availability (Fh) from in vitro metabolism
      data under linear conditions. Under nonlinear conditions, however, it is
      essential to consider the rate constant for the absorption (ka) for predicting Fh
      after oral administration, because the time profiles for the portal vein
      concentration depends on ka. In our study, we numerically solved the dispersion
      model under nonlinear conditions to propose a method to predict Fh after oral
      administration by taking ka into consideration. As a model compound, (S)-(-)-2,8
      dimethyl-3-methylene-1-oxa-8-azaspiro [4,5] decane-L-tartrate monohydrate (YM796)
      was used. After oral administration, we found that the dose-normalized AUC
      (AUCoral/dose) was markedly increased in rats from 5.0 x 10(-6) to 33 x 10(-6)
      hr/ml.kg as the dose increased from 1 to 10 mg/kg, whereas the same value was
      relatively constant in dogs (87.7 x 10(-6) to 105 x 10(-6) hr/ml.kg at 1 to 10
      mg/kg) and in humans (1260 x 10(-6) to 1768 x 10(-6) hr/ml.kg at 5 to 60
      mg/body). Kinetic analysis indicated that AUCoral could be accurately predicted
      at each dose if ka value was assumed as 0.07 min-1 for all animal species
      examined in our study. These results suggest that it is possible to predict Fh
      even if the metabolism is composed of non-linear process by considering the
      absorption rate into the portal vein.

PMID- 9655851
TI  - Effects of continuous alendronate treatment on bone mass and mechanical
      properties in ovariectomized rats: comparison with pamidronate and etidronate in
      growing rats.
AB  - Alendronate is a potent inhibitor of bone resorption. To investigate the
      relationship between antiresorptive activity and bone-related side effects, we
      studied the effect of 2 months of daily alendronate (0.04, 0.2, 1.0 or 5.0
      mg/kg/day) treatment on the strength of the femoral shaft and neck and on the
      bone mass of ovariectomized rats. The p.o. administration regimen began
      immediately after ovariectomy at 6 weeks of age, and the results were compared
      with pamidronate (0.2, 1.0 or 5.0 mg/kg/day) or etidronate (5.0, 25.0 or 125.0
      mg/kg/day) treatment. In the femoral epiphysis and neck, a preventive effect of
      alendronate on loss of bone mineral density was observed at the dose of 1.0
      mg/kg. The alendronate-treated group did not show significant alteration of the
      breaking load or the cross-sectional shape of the femoral midshaft. Similar
      results were obtained in the femoral neck strength and femoral neck geometry. In
      histomorphometric analysis of tibial metaphyses, alendronate inhibited the ratio
      of osteoid volume to tissue volume and the mineral apposition rate at a dose of
      0.2 mg/kg compared with the ovariectomized control. In contrast, etidronate
      tended to increase osteoid volume/bone volume at 125 mg/kg. From these results,
      we conclude that p.o. alendronate-treatment prevented the decrease in bone
      mineral density and maintained the mechanical properties of bone after
      ovariectomy without impairing of bone mineralization in growing rats.

PMID- 9655852
TI  - Dynorphin A as a potential endogenous ligand for four members of the opioid
      receptor gene family.
AB  - Dynorphin A is an endogenous opioid peptide that activates the kappa opioid
      receptor (KOR) with high potency. Some studies also showed that the distribution
      and functional activity of dynorphin A are not completely correlated with those
      of KOR, suggesting that dynorphin A may interact with other receptors. To
      investigate the possibility that dynorphin A may serve as an agonist for other
      opioid receptors, we took the advantage of the cloning of the three major types
      of opioid receptors, mu (MOR), delta (DOR) and KOR, and examined their affinity
      for and their activation by dynorphin A. We used mammalian cells transfected with
      each of the cDNA clones for the human receptors hMOR, hDOR, hKOR and showed that
      dynorphin A displaced [3H]-diprenorphine binding with Ki values in the nanomolar
      range at all three receptors. We also showed that, when hMOR, hDOR or hKOR was
      coexpressed with a G protein-activated potassium channel in Xenopus oocytes,
      dynorphin A induced a potassium current with EC50 values in the nanomolar range
      for all three receptors. Furthermore, we showed that the human hORLI, an opioid
      receptor-like receptor that has been identified as a novel member of the opioid
      receptor gene family, displayed dynorphin A binding and functional activation.
      These results indicate that dynorphin A is capable of binding to and functional
      activation of all members of the opioid receptor family, suggesting that, as a
      potential endogenous agonist, its activity in humans may involve interaction with
      other members of the opioid receptor family in addition to kappa receptors.

PMID- 9655853
TI  - Physiological red blood cell kinetic model to explain the apparent discrepancy
      between adenosine breakdown inhibition and nucleoside transporter occupancy of
      draflazine.
AB  - A physiological red blood cell (RBC) kinetic model is proposed for the adenosine
      (ADO) transport into erythrocytes and its subsequent intracellular deamination
      into inactive inosine (INO) and further breakdown into hypoxanthine (HYPO). The
      model and its parameters were based on previous studies investigating the
      kinetics of the biochemical mechanism of uptake and metabolism of ADO in human
      erythrocytes. Application of the model for simulations of the breakdown of ADO in
      a RBC suspension revealed that the predicted adenosine breakdown inhibition (ABI)
      of draflazine corresponded well with the ABI measured ex vivo. The model
      definitely explained the apparent discrepancy between the ex vivo measured ABI
      and the nucleoside transporter occupancy of draflazine. Intracellular deamination
      of ADO rather than its transport by the nucleoside transporter is the rate
      limiting step in the overall catabolism of ADO. Consequently, at least 90%
      occupancy of the transporter by draflazine is required to inhibit adenosine
      breakdown ex vivo substantially. Simulations on basis of the validated model were
      performed to evaluate the ABI for different experimental conditions and to mimic
      the clinical situation. The latter may be very helpful for the design of optimal
      dosing schemes of draflazine. It was demonstrated that the short half-life of
      released ADO was prolonged substantially in a dose-related manner after a
      continuous infusion of draflazine. Finally, the previously found different
      sigmoidal Emax relationships between the measured ABI and the concentrations of
      draflazine in plasma and whole blood could be explained by the ADO transport and
      breakdown RBC kinetic model and the capacity-limited specific RBC binding
      characteristics of draflazine.

PMID- 9655854
TI  - The role of peripheral mu opioid receptors in the modulation of capsaicin-induced
      thermal nociception in rhesus monkeys.
AB  - Capsaicin produces burning pain, followed by nociceptive responses, such as
      allodynia and hyperalgesia in humans and rodents. In the present study, when
      administered subcutaneously into the tail of rhesus monkeys, capsaicin (0.01-0.32
      mg) dose-dependently produced thermal allodynia manifested as reduced tail
      withdrawal latencies in 46 degrees C water, from a maximum value of 20 sec to
      approximately 2 sec. Coadministration of selective mu opioid agonists, fentanyl
      (0.003-0.1 mg) and (D-Ala2,N-Me-Phe4, Gly5-ol)-enkephalin (0.001-0.03 mg), dose
      dependently inhibited capsaicin-induced allodynia. This local antinociception was
      antagonized by small doses of opioid antagonists, quadazocine (0.03 mg) and
      quaternary naltrexone (1 mg), applied locally in the tail. However, these doses
      of antagonists injected s.c. in the back did not antagonize local fentanyl.
      Comparing the relative potency of either agonist or antagonist after local and
      systemic administration confirmed that the site of action of locally applied mu
      opioid agonists is in the tail. These results provide evidence that activation of
      peripheral mu opioid receptors can diminish capsaicin-induced allodynia in
      primates. This experimental pain model could be a useful tool for evaluating
      peripherally acting antinociceptive agents without central side effects and
      enhance new approaches to the treatment of inflammatory pain.

PMID- 9655855
TI  - Detailed mapping of ochratoxin A reabsorption along the rat nephron in vivo: the
      nephrotoxin can be reabsorbed in all nephron segments by different mechanisms.
AB  - Ochratoxin A (OTA) is a widespread nephrotoxin excreted to a substantial degree
      via the kidney. Previously we showed that [3H]OTA can be reabsorbed along the rat
      nephron in vivo (Zingerle et al., 1997). In this study we investigated in detail
      the contribution of different nephron segments to [3H]OTA reabsorption and
      determined the possible mechanisms involved by microinfusion and microperfusion
      experiments. At pH 6 (approximately 94% of OTA neutral), OTA is reabsorbed in all
      nephron segments investigated. The estimated fractional reabsorptions (FR) at a
      tubular load of 20 fmol/min are: proximal convoluted tubule (PCT), 14.8%;
      proximal straight tubule (PST), 27.4%; ascending limb of Henle's loop (ALH),
      13.6%; distal tubule (DT), 11.6%; collecting duct (CD), 24.6%; terminal CD,
      22.0%. At pH 8 (approximately 10% of OTA neutral) FR are as follows: PCT, 0%;
      PST, 25.9%; ALH, 14.0%; DT, 3.2%; CD, 8.2%. Thus, OTA reabsorption in PST and ALH
      in pH-independent. Reabsorption in PST but not in DT or CD was inhibited by
      sulfobromophthalein, a substrate of the apical organic anion carrier. L
      Phenylalanine did not reduce OTA reabsorption. After intravenous injection of
      unlabeled OTA, resulting in a plasma concentration of approximately 10(-5) mol/l,
      the FR of [3H]OTA during early proximal microinfusion was reduced slightly. From
      our results we conclude: 1) OTA can be reabsorbed in all nephron segments
      investigated. 2) Under physiological conditions the predominant sites of
      reabsorption are PST, ALH and terminal CD. 3) Reabsorption in PST and ALH is not
      pH-dependent. 4) pH-independent reabsorption in PST is mediated by the apical
      organic anion transporter (OAT-K1), whereas pH-dependent reabsorption in PCT is
      mediated by H(+)-dipeptide cotransporter(s). 5) Reabsorption also takes place
      during natural exposure, i.e., when OTA is present in plasma and renal tissue. 6)
      The high FR in ALH and CD explains, at least in part, the preferential impairment
      of postproximal functions and the accumulation in renal inner medulla and papila.

PMID- 9655856
TI  - Sigma ligands stimulate the electrical activity of frog pituitary melanotrope
      cells through a G-protein-dependent inhibition of potassium conductances.
AB  - We have investigated the effects of sigma ligands [1,3-di(2-tolyl)guanidine (DTG)
      and (+)-pentazocine] on the electrical activity of cultured frog pituitary
      melanotrope cells by using the patch-clamp technique. DTG and (+)-pentazocine (10
      microM each) induced a reversible depolarization associated with an increase in
      membrane resistance and action potential firing. In voltage-clamp experiments,
      DTG and (+)-pentazocine elicited inward currents whose intensity augmented with
      membrane depolarization. The currents vanished or reversed between -90 and -100
      mV, at values close to the K+ equilibrium potential (E(K)+ = -102 mV). DTG (2-500
      microM) and (+)-pentazocine (0.2-200 microM) reduced the outward delayed
      rectifier K+ current [IK (V)] in a dose-dependent manner with EC50 of 64 and 37
      microM, respectively. In contrast, naloxone (50 microM) and pirenzepine (10
      microM) did not affect the sigma ligand-induced inhibition of IK (V). Addition of
      guanosine-5'-O-(3-thiophosphate) in the pipette solution irreversibly sustained
      the DTG-induced current whereas guanosine-5'-O-(2-thiodiphosphate) virtually
      suppressed the response. Cholera toxin-pretreatment (1 microgram/ml; 18 hr)
      abolished the inward current and the inhibition of IK (V) induced by sigma
      ligands. In contrast, pretreatment with pertussis toxin (1 microgram/ml; 18 hr)
      had no effect. Taken together, these data indicate that DTG and (+)-pentazocine
      activate the electrical activity of cultured frog melanotrope cells by reducing
      both a tonic K+ current and a voltage-dependent [IK (V)] K+ conductance through
      the activation of a cholera toxin-sensitive G-protein.

PMID- 9655857
TI  - Citalopram enhances the activity of chloroquine in resistant plasmodium in vitro
      and in vivo.
AB  - Citalopram, is an extremely potent inhibitor of neuronal serotonin reuptake. It
      is structurally unrelated to other antidepressants, but it contains the chemical
      features associated with reversal of drug resistance and exhibits minimal
      cardiotoxic side effects and fewer of the anticholinergic and adrenolytic side
      effects associated with other psychotropic agents. Sensitivity tests to
      citalopram alone and in combination with chloroquine were performed against
      chloroquine-resistant and chloroquine-sensitive strains of Plasmodium falciparum
      and Plasmodium chabaudi. Citalopram alone showed intrinsic activity against the
      chloroquine-resistant strains of P. falciparum (IC50 = 1.51 +/- .6 microM) but
      only limited activity against the chloroquine-sensitive strain (IC50 = 33.27 +/-
      5.87 microM) and no activity in vivo. The interaction of chloroquine and
      citalopram in vitro resulted in a synergistic response in the chloroquine
      resistant strain but there was no interaction between the drugs in the
      chloroquine-sensitive strain--a pattern found with other reversal agents.
      Citalopram enhanced chloroquine susceptibility in both strains of P. chabaudi,
      however, the potentiating effect was seen at lower doses in the chloroquine
      resistant strain. The results of this study suggest that citalopram may have
      potential as a chemosensitizer in Plasmodium infections on the basis of the low
      toxicity of citalopram at concentrations potentiating chloroquine activity both
      in vitro and in vivo.

PMID- 9655858
TI  - A new sodium/hydrogen exchange inhibitor, EMD 85131, limits infarct size in dogs
      when administered before or after coronary artery occlusion.
AB  - Administration of inhibitors of the Na+/H+ exchanger (NHE) have been shown to
      produce cardioprotective effects in a number of animal models of ischemia
      reperfusion injury; however, controversy still exists as to the efficacy of these
      agents when administered just before reperfusion. To address this question, the
      efficacy of several doses of a new selective NHE-1 isoform inhibitor (IC50 for
      inhibition of 22Na uptake in NHE-1 expressing mouse fibroblast cells = 10.4 +/-
      1.0 nM), EMD 85131 (2-methyl-5-methylsulfonyl-1-(1-pyrrollyl)-benzoyl-guanidine),
      was tested in a canine infarct model in which the left anterior descending
      coronary artery was occluded for 60 min followed by 3 hr of reperfusion. EMD
      85131 (0.75 or 3.0 mg/kg) was infused for 15 min before left anterior descending
      occlusion or 15 min before reperfusion. Infarct size was determined by use of the
      triphenyltetrazolium chloride histochemical stain and was expressed as a percent
      of the area at risk. EMD 85131 (0.75 or 3.0 mg/kg) administered before left
      anterior descending occlusion produced a marked (*P < .05) and dose-related
      reduction in IS/AAR (24.3 +/- 3.6, control; 9.3 +/- 3.4%, EMD 0.75; 6.4 +/- 2.3%,
      EMD 3.0). These two doses of EMD also produced significant (*P < .05) reductions
      in infarct size/area at risk (12.2 +/- 2.1%, EMD 0.75; 13.0 +/- 2.9%, EMD 3.0)
      when administered 15 min before reperfusion. These results suggest that selective
      NHE-1 inhibitors are able to markedly reduce infarct size when given before or
      during ischemia and also suggest that these compounds may have clinical utility
      when administered after the initiation of an ischemic insult.

PMID- 9655859
TI  - Synthesis and characterization of diazomethylarachidonyl ketone: an irreversible
      inhibitor of N-arachidonylethanolamine amidohydrolase.
AB  - N-Arachidonylethanolamine (AEA), a putative endogenous agonist of neuronal (CB1)
      cannabinoid receptors, is a substrate for N-arachidonylethanolamine
      amidohydrolase (AEA amidohydrolase), a serine amidase present in cell membranes.
      Following a strategy that has been used to develop inhibitors that covalently
      bind to the active site of serine peptidases, diazomethyl arachidonyl ketone
      (DAK) was synthesized and its effects on AEA amidohydrolase were determined. DAK
      inhibits the hydrolysis of AEA by rat brain membranes with an IC50 value of 0.5
      microM. At low concentrations, DAK reduces the Vmax and increases the K(m) of the
      enzyme for its substrate AEA, which suggests that it is both a competitive and
      noncompetitive inhibitor. At higher concentrations, DAK inhibition is completely
      noncompetitive. DAK inhibition of membrane-associated AEA amidohydrolase is
      irreversible because hydrolytic activity is not restored with extensive washing
      or dialysis of the membranes. Furthermore, DAK inhibition is not reversible by
      anion exchange chromatography of the subsequently solubilized enzyme. In
      contrast, DAK inhibition of detergent-solubilized enzyme exhibits competitive
      kinetics and is reversible upon ion exchange chromatography. Exposure of C6
      glioma cells to DAK results in concentration-related inhibition of AEA
      amidohydrolase activity in cellular membranes with an IC50 value of 0.3 microM.
      In summary, these studies demonstrate that DAK is an irreversible inhibitor of
      AEA amidohydrolase in its native membrane and provides a useful tool with which
      to study the role of AEA amidohydrolase in the termination of action of AEA.

PMID- 9655860
TI  - Species- and gender-related differences in cyclosporine/prednisolone/sirolimus
      interactions in whole blood lymphocyte proliferation assays.
AB  - Cyclosporin A (CyA), prednisolone (Pred) and sirolimus (Sir) inhibit lymphocyte
      proliferation at the cytokine transcription (CyA and Pred) or signal transduction
      (Sir) levels. Their double and triple interactions were studied on lectin-induced
      proliferation of whole blood lymphocytes (WBLP) from male and female humans,
      rabbits and rats. Isobols along with the Universal Response Surface Approach were
      used to describe and quantify the nature and intensity of drug interactions by
      determining alpha values. CyA was always less potent than Pred and Sir while
      these two compounds were relatively equipotent. Species-related differences were
      observed with single drugs. Rabbit WBLP were resistant to Pred action (Imax =
      67%) and rats were more sensitive to Pred (IC50 = 9.1 nM in females) and Sir (2.8
      nM) actions than humans (32 and 55 nM). Gender differences were observed but were
      not consistent across species. All double-drug combinations were synergistic, and
      combinations containing Pred were 10 to 100 times more synergistic in rabbits
      (alpha Pred/Sir = 213 and alpha CyA/Pred = 147 in males) than in rats (12 and
      2.1) or humans (3.7 and 5.7) in relation to the lower efficacy of Pred. Double
      combination alpha values were able to describe CyA/Pred/Sir triple combination
      effects. These studies indicate that CyA, Pred and Sir act and synergistically
      interact in vitro in species- and gender-dependent fashions. Adrenalectomized
      rats better resemble humans in these responses. WBLP are useful in various
      species in determining immunosuppressive drug action and interactions.

PMID- 9655861
TI  - Influence of lubeluzole on voltage-sensitive Ca++ channels in isolated rat
      neurons.
AB  - Lubeluzole is neuroprotective in a photochemical stroke model, whereas the (R)
      enantiomer of the same molecule is not [De Ryck M, Keersmaekers R, Duytschaever
      H, Claes C, Clincke G, Janssen M and Van Reet G (1996) J Pharmacol Exp Ther
      279:748-758]. We investigated the effects of lubeluzole and the (R)-enantiomer on
      voltage-sensitive Ca++ channels of isolated rat dorsal root ganglion cells, using
      whole-cell voltage-clamp, with Ba++ as the charge carrier. Both compounds blocked
      the low-voltage-activated Ba++ current (iLVA or T current) with an IC50 value of
      1.2 microM. Lubeluzole and the (R)-enantiomer also blocked the high-voltage
      activated calcium channel current (iHVA), with IC50 values of 2.6 and 3.5 microM,
      respectively, and accelerated the apparent inactivation of iHVA. This
      acceleration was more pronounced with lubeluzole than with the (R)-enantiomer at
      3 and 10 microM. Both compounds produced a clear tonic block of iLVA and iHVA,
      even in the absence of previous stimulation. Lubeluzole and the (R)-enantiomer
      induced a negative shift of the inactivation curve of iLVA and showed down the
      recovery from inactivation. This resulted in a stronger inhibition of iLVA at
      more depolarized conditioning potentials and higher stimulation frequencies. The
      block of iHVA was voltage and frequency dependent. Lubeluzole and the (R)
      enantiomer also blocked iHVA in isolated rat superior cervical ganglion cells and
      cerebellar Purkinje cells. The Ca++ channel-blocking properties of lubeluzole may
      contribute to its neuroprotective effect. However, the small difference between
      the two enantiomers in inhibition of Ca++ channel currents does not explain the
      stereospecificity of the neuroprotective properties of lubeluzole in vitro and in
      vivo.

PMID- 9655862
TI  - Nitric oxide-releasing oxatriazole derivatives inhibit human lymphocyte
      proliferation by a cyclic GMP-independent mechanism.
AB  - Two novel nitric oxide (NO)-releasing oxatriazole derivatives, GEA 3162 and GEA
      3175, and an earlier known NO donor, S-nitroso-N-acetylpenicillamine (SNAP),
      inhibited cell proliferation and enhanced cGMP production in a concentration
      dependent manner in human lymphocytes activated by lectin mitogen concanavalin A
      (ConA). The possible mediator role of cGMP in the antiproliferative action of NO
      donors was tested by pharmacological means. An inhibitor of guanylate cyclase, 1H
      [1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one, inhibited NO donor-induced cGMP
      production, whereas the antiproliferative action of NO donors remained unaltered.
      Phosphodiesterase inhibitors zaprinast and 3-isobutyl-1-methylxanthine
      potentiated and prolonged NO donor-induced increase in the concentrations of cGMP
      but did not enhance the antiproliferative action of NO donors. In addition, two
      analogs of cGMP, 8-bromo-cGMP and a more cell-permeable compound, 8-p
      chlorophenylthio-cGMP, did not inhibit ConA-stimulated lymphocyte proliferation
      when used in concentrations of up to 300 microM. At millimolar concentrations, 8
      bromo-cGMP had a moderate inhibitory action. These results suggest that nitric
      oxide-releasing oxatriazole derivatives inhibit proliferative responses in human
      lymphocytes by a cGMP-independent manner.

PMID- 9655863
TI  - Effects of local anesthetics on acetylcholine-induced desensitization of guinea
      pig ileal longitudinal muscle.
AB  - We investigated which of the major actions of local anesthetics (i.e., inhibition
      of phospholipase A2, interaction with Ca++ channels or blockade of receptor) was
      responsible for the inhibition of acetylcholine-induced desensitization in guinea
      pig ileal longitudinal muscle. Desensitization was inhibited by amine local
      anesthetics and related compounds in the order of potency quinacrine >
      chloroquine > tetracaine > procaine. Potent phospholipase A2 inhibitors,
      manoalide (1 microM) and p-bromophenacyl bromide (5 microM) had no effect on
      desensitization. The rank order of interaction of local anesthetics with Ca++
      channels did not agree with the potency order of inhibition of desensitization.
      These data indicated that local anesthetics did not inhibit desensitization
      through their inhibition of phospholipase A2 or their interaction with Ca++
      channels. Quinacrine, chloroquine, tetracaine and procaine inhibited [3H]N
      methylscopolamine binding to solubilized membrane with pKi values of 7.03 +/-
      0.10, 6.59 +/- 0.02, 5.40 +/- 0.10 and 5.03 +/- 0.04 and reduced receptor
      occupancy by agonist from 99.0% (without inhibitor) to 96.8%, 95.1%, 89.4% and
      49.8%, respectively, under the conditions where each drug induced half-maximum
      inhibition of desensitization, indicating that they (except for procaine) did not
      effectively block muscarinic receptors. However, the combined dose-ratio test
      showed that some of these drugs (quinacrine and chloroquine) interacted
      noncompetitively at muscarinic receptors. Therefore, these drugs could have bound
      to an allosteric site on the receptor, modified agonist-receptor interaction and
      thus inhibited the pathway specific to the desensitization process.

PMID- 9655864
TI  - Therapeutic effects of dopamine D1/D2 receptor agonists on detrusor hyperreflexia
      in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned parkinsonian cynomolgus
      monkeys.
AB  - The effects of dopamine receptor agonists on urinary bladder function were
      evaluated in normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      lesioned parkinsonian cynomolgus monkeys to investigate the therapeutic efficacy
      in the treatment of urinary symptoms in Parkinson's disease. Under ketamine
      anesthesia, cystometrograms exhibited significant reduction in the volume
      threshold for the micturition reflex in MPTP-lesioned parkinsonian monkeys when
      compared with those of normal monkeys. The selective dopamine D2 receptor agonist
      bromocriptine significantly reduced the bladder volume threshold for the
      micturition reflex by 25 to 30% in both normal and MPTP-lesioned animals. The
      nonselective D1/D2 receptor agonist pergolide significantly reduced the bladder
      volume threshold by 22% in normal monkeys, but increased the volume threshold by
      50% in MPTP-lesioned parkinsonian monkeys. Another D1/D2 agonist (5R,8R,10R)-6
      methyl-8-(1,2,4-triazol-1-ylmethyl) ergoline maleate (BAM-1110) also increased
      the bladder volume threshold (by 80%) in parkinsonian monkeys without significant
      effects on the micturition reflex in normal monkeys. The reduction in the volume
      threshold by bromocriptine in both normal and MPTP-treated groups and by
      pergolide in normal monkeys was suppressed by pretreatment with the selective D2
      antagonist sulpiride, whereas the increment in the volume threshold by pergolide
      and BAM-1110 in parkinsonian monkeys was antagonized by pretreatment with the
      selective D1 antagonist SCH 23390, but not by sulpiride. These findings suggest
      that concurrent activation of D1/D2 receptors, rather than selective stimulation
      of D2 receptors, might be beneficial for treating urinary symptoms caused by
      detrusor hyperreflexia in Parkinson's disease.

PMID- 9655865
TI  - M2 muscarinic receptors inhibit forskolin- but not isoproterenol-mediated
      relaxation in bovine tracheal smooth muscle.
AB  - The ability of the M2 muscarinic receptor to inhibit the relaxant effects of
      forskolin and isoproterenol was investigated in bovine trachea. In most
      experiments, we measured contractile responses to oxotremorine-M in smooth muscle
      isolated from bovine trachea in which a majority of M3 receptors were inactivated
      by treatment with N-(2-chloroethyl)-4-piperidinyl diphenylacetate. In the
      presence of histamine (20 microM), the histamine H2 antagonist cimetidine (10
      microM) and forskolin (4 microM), responses to oxotremorine-M were antagonized by
      [[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5, 11-dihydro-6H
      pyrido[2,3b][1,4]benzodiazepine-6-one (1 microM) in a manner consistent with
      contractions mediated predominantly by M2 receptors. When similar experiments
      were conducted in the presence of isoproterenol (0.1 microM) instead of
      forskolin, contractions were antagonized in a manner consistent with an M3
      receptor-mediated response. In similar experiments, we measured the relaxant
      potency of isoproterenol and forskolin against histamine-induced contractions in
      N-(2-chloroethyl)-4-piperidinyl diphenylacetate-treated trachea. By itself,
      oxotremorine-M (7.5 nM) had no contractile effect; however, it caused a
      substantial reduction in the relaxant potency of forskolin although having little
      effect on that of isoproterenol. These experiments establish that M2 receptors
      inhibit the relaxant effects of forskolin, but not isoproterenol. In untreated
      tissues, the relaxant responses to isoproterenol and forskolin were 10.8- and
      14.2-fold more potent, respectively, against histamine than against oxotremorine
      M-induced contractions of equal magnitude. Similarly, the maximal stimulation of
      cAMP accumulation elicited by isoproterenol and forskolin was inhibited 58 and
      62%, respectively, in the presence of oxotremorine-M (80 nM) compared to that
      measured in the presence of histamine (20 microM). Analysis of the data indicated
      that isoproterenol elicited relaxation at concentrations well beyond those that
      stimulated maximal levels of cAMP accumulation. Our results indicate that part of
      the relaxant response to isoproterenol is mediated through a non-cAMP-dependent
      mechanism, and that this mechanism is largely unopposed by the M2 receptor.

PMID- 9655866
TI  - Maintenance of recombinant type A gamma-aminobutyric acid receptor function: role
      of protein tyrosine phosphorylation and calcineurin.
AB  - In the present study, rundown of gamma-aminobutyric acid (GABA)-activated Cl-
      channels was studied in recombinant GABAA receptors stably expressed in human
      embryonic kidney cells (HEK 293), with conventional whole-cell and amphotericin B
      perforated patch recording. When [ATP]i was lowered to 1 mM and resting [Ca++]i
      was buffered to a relatively high level, the response of alpha 3 beta 2 gamma 2
      GABAA receptors to relatively low [GABA] (up to 50 microM) did not show rundown
      in the whole-cell configuration. However, high [GABA] (greater than 200 microM)
      induced significant rundown, which was observed by decreases in both the maximum
      GABA-induced current and GABA EC50. Rundown was prevented completely with a
      solution containing 4 mM Mg(++)-ATP and low resting [Ca++]i, or during perforated
      patch recording. The magnitude of rundown was comparable in alpha 1 beta 2 gamma
      2 and beta 2 gamma 2 receptors. Neither stimulation nor inhibition of protein
      kinase A or protein kinase C had a significant effect on rundown. However, sodium
      metavanadate, an inhibitor of protein tyrosine phosphatase, significantly reduced
      rundown. In addition, inhibition of protein tyrosine kinase activity by either
      genistein or lavendustin A induced rundown of the GABA response. Inhibition of
      the Ca++/calmodulin-dependent phosphatase calcineurin with fenvalerate also
      prevented rundown of the response to GABA. Our results demonstrate that rundown
      of GABAA receptor function is concentration-dependent, due to depletion of ATP
      and/or unbuffered [Ca++]i, and does not depend on the presence or subtype of the
      alpha subunit. We propose that protein phosphorylation at a tyrosine kinase
      dependent site, and a distinct unidentified site, which is dephosphorylated by
      calcineurin, maintains the function of GABAA receptors.

PMID- 9655867
TI  - Alterations in 8-hydroxy-2-(dipropylamino)tetralin-induced neuroendocrine
      responses after 5,7-dihydroxytryptamine-induced denervation of serotonergic
      neurons.
AB  - In the present study, we examined denervation-induced changes in the sensitivity
      of hypothalamic postsynaptic serotonin1A (5-HT1A) receptor function with respect
      to changes in the dose-dependent elevation in plasma hormones
      [adrenocorticotropic hormone (ACTH), corticosterone, prolactin, oxytocin,
      prolactin, renin and vasopressin] by the 5-HT1A agonist 8-hydroxy-2
      (dipropylamino)tetralin (8-OH-DPAT). Rats received intracerebroventricular
      (i.c.v.) injections of the serotonin neurotoxin 5,7-dihydroxytryptamine (5,7-DHT)
      or vehicle (0.1% ascorbate in saline) 3 weeks before challenge with increasing
      doses of 8-OH-DPAT (0, 10, 50 or 200 micrograms/kg s.c.). The effectiveness of
      5,7-DHT-induced destruction of serotonergic neurons was confirmed by a 93%
      reduction in [3H]paroxetine-labeled 5-HT uptake sites in the hypothalamus. No
      changes in basal levels of ACTH, corticosterone, oxytocin, prolactin, renin and
      vasopressin were observed in rats that received i.c.v. 5,7-DHT injections. The
      dose-response curves for 8-OH-DPAT-induced elevations of plasma corticosterone
      and prolactin levels were shifted to the left in rats treated with 5,7-DHT,
      whereas no significant difference in the ACTH dose-response curve was observed
      between rats treated with vehicle and rats treated with 5,7-DHT. In contrast, the
      maximal oxytocin response to 8-OH-DPAT was attenuated in rats treated with 5,7
      DHT. A 5,7-DHT-induced decline in the synthesis of oxytocin could explain this
      phenomenon. Although 8-OH-DPAT did not increase plasma levels of renin or
      vasopressin in rats treated with vehicle, 8-OH-DPAT produced an elevation (75%)
      in plasma renin concentration but not in vasopressin levels in rats that received
      i.c.v. injections of 5,7-DHT. No change was observed in [3H]8-OH-DPAT labeled 5
      HT1A receptors in the hypothalamus. In summary, denervation of hypothalamic
      serotonergic nerve terminals produces supersensitivity of some neuroendocrine
      responses to 8-OH-DPAT independent of changes in the density of hypothalamic 5
      HT1A receptors.

PMID- 9655868
TI  - Provisional mapping of quantitative trait loci for chronic ethanol withdrawal
      severity in BXD recombinant inbred mice.
AB  - Male mice from C57BL/6J (B6), DBA/2J (D2) and their 25 recombinant inbred (RI)
      strains were exposed to ethanol (EtOH) vapor (3.0-9.0 mg EtOH/liter of air) for
      72 hr. Mice were selected such that each strain averaged 1.34 to 1.59 mg of
      EtOH/ml of blood on withdrawal. Control groups and EtOH-exposed groups were
      tested hourly for handling-induced convulsions (HIC) for 10 hr and at hr 24 and
      25. Strain withdrawal severity was indexed as the area under the 25-hr HIC curve
      for the EtOH group minus that strain's equivalent value for the control group.
      Genome-wide quantitative trait locus (QTL) analyses correlating strain means with
      allelic status at > 1500 markers identified 10 chromosomal regions at P < .01.
      These provisionally identified QTLs were on chromosomes 1 (2 QTLs), 3, 9 (2
      QTLs), 10, 12, 13, 15 and 18. Multiple regression analysis using the four most
      influential QTLs revealed that these loci controlled 86% of the genetic variance.
      A QTL mapped to distal chromosome 1 (P < .001) is in the same region as one
      previously definitively mapped for acute alcohol withdrawal, as well as one
      mapped for acute pentobarbital withdrawal. Several of the QTLs map near potential
      candidate genes. These provisional linkages will now be confirmed or rejected
      using additional genetically segregating populations.

PMID- 9655869
TI  - Effects of full D1 dopamine receptor agonists on firing rates in the globus
      pallidus and substantia nigra pars compacta in vivo: tests for D1 receptor
      selectivity and comparisons to the partial agonist SKF 38393.
AB  - Many studies have used the D1 agonist SKF 38393 to characterize D1 receptor
      influences on firing rates in basal ganglia nuclei in vivo. However, SKF 38393 is
      a partial agonist and so may not be ideal for delineating D1 receptor effects.
      This study characterizes the effects of four full D1 agonists, SKF 82958 (chloro
      APB), SKF 81297 (6-chloro-PB), dihydrexidine and A-77636, on the firing rates of
      midbrain dopamine and globus pallidus neurons. Recordings were done in fully
      anesthetized or paralyzed, locally anesthetized rats, and drugs were given
      systemically intravenously. Dihydrexidine, SKF 81297 and A-77636 were free of
      rate effects on midbrain dopamine neurons (up to 10.2 mg/kg) and also did not
      antagonize the inhibitory effects of quinpirole. In contrast, SKF 82958 strongly
      inhibited dopamine cells through activation of D2 autoreceptors (ED50 = 0.70
      mg/kg). Of these drugs, SKF 82958 also was the only one to increase pallidal unit
      firing rates when given alone (at 5.0 but not 1.0 mg/kg); the other compounds
      appeared to be selective for postsynaptic D1 receptors. The results suggest that
      SKF 82958 may be more properly classified as a mixed D1/D2 agonist. In addition,
      all four agonists strongly potentiated the pallidal response to quinpirole,
      demonstrating a D1 receptor potentiation of D2 receptor effects. The results
      support the role of D1 receptors in the midbrain and globus pallidus as
      previously characterized with SKF 38393. The similar actions of partial and full
      D1 agonists in these systems support evidence for a D1 receptor reserve and
      possibly an effector system other than adenylate cyclase.

PMID- 9655870
TI  - Stimulation of guanosine-5'-O-(3-[35S]thio)triphosphate binding by endogenous
      opioids acting at a cloned mu receptor.
AB  - The ability of endogenous opioids to activate G proteins was measured in
      membranes from C6 rat glioma cells stably expressing a cloned rat mu receptor.
      Peptides representing each of the three known families of endogenous opioids
      (enkephalins, endorphins and dynorphins) were studied, as well as two recently
      discovered endogenous opioids, endomorphin-1 and -2, which are thought to
      represent a fourth family of endogenous opioid peptides. Stimulation of guanosine
      5'-O-(3-[35S]thio)triphosphate ([35S]GTP gamma S) binding to membranes was used
      as a measure of G protein activation. It was possible to differentiate high
      efficacy compounds such as Tyr-D-Ala-Gly-(Me)Phe-Gly-ol from lower-efficacy
      agonists such as morphine or meperidine. Met- and leu-enkephalin, beta endorphin
      and dynorphin A were all found to have high efficacy at the mu receptor, as were
      the peptide fragments beta endorphin-1(1-27) and dynorphin A-(1-13). Endomorphin
      1 and -2 were found to be partial agonists, capable of both stimulating [35S]GTP
      gamma S binding and antagonizing the stimulation produced by the higher-efficacy
      agonist Tyr-D-Ala-Gly-(Me)Phe-Gly-ol. Binding affinities for the opioid agonists
      at the cloned mu receptor were measured by the displacement of radiolabeled
      antagonist. It was found that the Ki values closely matched the EC50 values for
      [35S]GTP gamma S binding stimulation, indicating that a large receptor reserve
      does not exist for the complete activation of G proteins in this system.

PMID- 9655871
TI  - A role for tryptase in the activation of human mast cells: modulation of
      histamine release by tryptase and inhibitors of tryptase.
AB  - Tryptase, the most abundant protein product of human mast cells is emerging as an
      important mediator and target for therapeutic intervention in allergic disease.
      We have investigated the potential of tryptase and inhibitors of tryptase to
      modulate histamine release from human mast cells. Addition of purified human
      tryptase in concentrations ranging from 1 to 100 mU/ml stimulated a concentration
      dependent release of histamine from cells dispersed from tonsil, although not
      from skin tissue. The reaction dependent on an intact catalytic site being
      inhibited by heat inactivation of the enzyme, or by preincubating with the
      tryptase inhibitors APC366 or leupeptin or the tryptic substrate N-benzoyl-DL
      arginine-p-nitroanilide (BAPNA). Tryptase-induced histamine release took
      approximately 6 min to reach completion, appeared to require exogenous calcium
      and magnesium, and on the basis of inhibition by antimycin A and 2-deoxy-D
      glucose, seemed to be a noncytotoxic process. Pre-incubation of cells with
      tryptase at concentrations that were suboptimal for histamine release had little
      effect on their responsiveness to anti-immunoglobulin (Ig) E or to calcium
      ionophore A23187, but at higher concentrations their subsequent activation was
      inhibited. APC366 significantly inhibited histamine release induced by anti-IgE
      or calcium ionophore from both tonsil and skin cells, with up to 90% inhibition
      being observed at a concentration of 100 microM with skin. IgE-dependent
      histamine release was inhibited also by leupeptin, benzamidine and BAPNA.
      Tryptase may act as an amplification signal for mast cell activation, and this
      could account at least partly for the potent mast cell stabilizing properties of
      tryptase inhibitors.

PMID- 9655872
TI  - Effects of nitric oxide on adenylyl cyclase stimulation in N18TG2 neuroblastoma
      cells.
AB  - The addition of nitric oxide (NO), in the form of either donor compounds or
      nitric oxide gas, inhibits hormone-stimulated cAMP accumulation in N18TG2 cells.
      Hormone receptors and Gs are not targets of NO because forskolin-stimulated cAMP
      accumulation is also inhibited. The inhibitory effect of NO is not altered by
      pretreatment of cells with pertussis toxin, indicating that Gi is not mediating
      the effect of NO. cAMP accumulation in these cells is not altered by cell
      incubation with Ca++ ionophore or calmidazolium, indicating that calmodulin is
      not the target for NO. Experiments also rule out changes in phosphodiesterase or
      cGMP as mediators of the effect of NO. Cell incubation with superoxide dismutase
      in the presence or absence of catalase indicate that nitric oxide is the reactive
      species. The inhibitory action of nitric oxide is readily reversed, allowing full
      recovery of hormone and forskolin stimulation within 20 min of incubation in the
      absence of nitric oxide. The sum of the data indicate that NO targets either the
      adenylyl cyclase itself, or a regulatory component distinct from G proteins or
      calmodulin, to inhibit activation of the enzyme.

PMID- 9655873
TI  - Regulation of organic cation transport in IHKE-1 and LLC-PK1 cells. Fluorometric
      studies with 4-(4-dimethylaminostyryl)-N-methylpyridinium.
AB  - The regulation of transport of the fluorescent organic cation 4-(4
      dimethylaminostyryl)-N-methylpyridinium (ASP+) by renal proximal tubular organic
      cation transport was studied in IHKE-1 and LLC-PK1 cells with a recently
      established fluorometric technique (Stachon et al., 1996, 1997). Stimulation of
      Ca++/diacylglycerol-dependent protein kinase by 1,2-dioctanoyl glycerol (DOG;
      0.01-1 mumol/l, n = 7), ATP (0.1 mmol/l, n = 9), oxytocin (0.1 mumol/l, n = 6)
      and bradykinin (1 mumol/l, n = 7) resulted in an increase of ASP+ accumulation in
      IHKE-1 cells by 35 +/- 9% (DOG), 65 +/- 30% (ATP), 66 +/- 14% (bradykinin) and 70
      +/- 20% (oxytocin) as compared with basal conditions, whereas ASP+ accumulation
      was slightly reduced in LLC-PK1 cells after stimulation with DOG (1 mumol/l, -20
      +/- 7%, n = 10) and angiotensin II (0.1 nmol/l, -20 +/- 5%, n = 6). ASP+
      accumulation in IHKE-1 cells also was increased by 0.5 mumol/l (20 +/- 8%, n = 8)
      and 1 mumol/l forskolin (35 +/- 13%, n = 19), and by 8-bromo-cAMP (1 mumol/l, 125
      +/- 25%, n = 9), both activators of the cAMP-dependent protein kinase (PKA).
      Activation of the cGMP-dependent protein kinase (PKG) by human atrial natriuretic
      peptide (10 nmol/l, n = 10) or 8-bromo-cGMP (0.1 mmol/l, n = 12) resulted in an
      increase of 35 +/- 5% and 28 +/- 6%, respectively. Activation of PKA and PKG had
      no influence on ASP+ transport in LLC-PK1 cells. Regulation of ASP+ uptake by
      these two cell lines may be caused by direct phosphorylation of the organic
      cation transporters involved or by regulation of trafficking of the transporters
      to the membrane. Differences in the organic cation transporter isoforms or
      alternatively, in the trafficking may contribute to the distinct regulation of
      ASP+ transport in IHKE-1 and LLC-PK1 cells.

PMID- 9655874
TI  - alpha 5 Subunit alters desensitization, pharmacology, Ca++ permeability and Ca++
      modulation of human neuronal alpha 3 nicotinic receptors.
AB  - Functional effects of human alpha 5 nicotinic ACh receptor (AChR) subunits
      coassembled with alpha 3 and beta 2 or with alpha 3 and beta 4 subunits, were
      investigated in Xenopus oocytes. The presence of alpha 5 subunits altered some
      properties of both alpha 3 AChRs and differentially altered other properties of
      alpha 3 beta 2 AChRs vs. alpha 3 beta 4 AChRs. alpha 5 subunits increased
      desensitization and Ca++ permeability of all alpha 3 AChRs. The Ca++
      permeabilities of both alpha 3 beta 2 alpha 5 and alpha 3 beta 4 alpha 5 AChRs
      were comparable to that of alpha 7 AChRs. As we have shown previously, alpha 5
      subunits increased the ACh sensitivity of alpha 3 beta 2 AChRs 50-fold but had
      little effect on alpha 3 beta 4 AChRs. alpha 5 caused only subtle changes in the
      activation potencies of alpha 3 AChRs for nicotine, cytisine and 1,1-dimethyl-4
      plenylpiperazinium (DMPP). However, alpha 5 increased the efficacies of nicotine
      and DMPP on alpha 3 beta 2 AChRs but decreased them on alpha 3 beta 4 AChRs.
      Immunoisolation of cloned human AChRs expressed in oocytes showed that alpha 5
      efficiently coassembled with alpha 3 plus beta 2 and/or beta 4 subunits. As
      expected, human AChRs immunoisolated from SH-SY5Y neuroblastoma cells showed that
      AChRs containing alpha 3 and probably alpha 5 subunits were present, but alpha 4
      AChRs were not. In brain, by contrast, alpha 4 beta 2 AChRs were shown to
      predominate over alpha 3 AChRs. Some of the brain alpha 4 beta 2 AChRs were found
      to contain alpha 5 subunits.

PMID- 9655875
TI  - Heterologous expression of various P-glycoproteins in polarized epithelial cells
      induces directional transport of small (type 1) and bulky (type 2) cationic
      drugs.
AB  - We recently showed that absence of mdr1-type P-glycoprotein (P-gp) in mice
      resulted in profoundly reduced hepatic and intestinal clearance of type 1 and
      type 2 cationic drugs compared with that in wild-type mice. These data strongly
      support the concept that mdr1-type P-gps are involved in the disposition of
      cationic amphiphilic drugs from the body. We tested the hypothesis that mdr1-type
      P-gps are involved in the transmembrane transport of organic cations in
      epithelial cells expressing various drug-transporting P-gps. Therefore,
      transepithelial transport of the P-gp substrate vinblastine, the steroidal (type
      2) cation vecuronium, the relatively small (type 1) cationic compound
      azidoprocainamide methoiodide and the aliphatic cation tri-n-butylmethylammonium
      were measured. Apical expression of the mdr1a, mdr1b or MDR1 gene in confluently
      grown polarized transformed LLC-PK1 cells resulted in highly enhanced apical
      directed secretion of all the drugs tested compared with controls. The vectorial
      transport of tri-n-butylmethylammonium in the apical direction in the P-gp
      (over)expressing cells could be inhibited by vinblastine. The present
      observations show that apical secretion of type 1 as well as of type 2 organic
      cations is enhanced significantly in the presence of apical expressed mdr1-type P
      gp. These findings provide evidence for the involvement of drug-transporting P-gp
      in transmembrane transport of various organic cations, including relatively small
      molecular weight aromatic and aliphatic compounds.

PMID- 9655876
TI  - Modulation of intestinal estrogen receptor by ovariectomy, estrogen and growth
      hormone.
AB  - Ovarian hormone deficiency decreases and estrogen (E2) and growth hormone (GH)
      administrations increase intestinal absorption of calcium (Ca++). However, the
      underlying mechanisms are uncertain. To examine whether alterations in the
      binding characteristics of intestinal estrogen receptors (ERs) are involved, we
      developed and validated methods for simultaneous measurement of intestinal ERs in
      cytosolic and nuclear fractions and applied these techniques to four groups of
      female rats: sham-operated, ovariectomized (Ovx), Ovx + 5 micrograms E2/kg
      b.wt./day and Ovx + 8 mg GH/kg. b.wt./day. All animals were killed on day 21, and
      mucosal cells harvested from the duodenum for ER determination. The cytosolic and
      nuclear ERs were 117.2 +/- 2.7 fmol/mg protein and 64.9 +/- 1.2 fmol/mg DNA,
      respectively, in sham-operated rats and decreased by 16.1% and 17.0% to 98.4 +/-
      1.7 fmol/mg protein and 53.8 +/- 1.3 fmol/mg DNA, respectively in Ovx rats (P <
      .001). E2 therapy prevented completely the decrease in cytosolic and nuclear ERs
      that occurred in Ovx rat (126.1 +/- 2.9 fmol/mg protein and 68.0 +/- 3.0 fmol/mg
      DNA, respectively, in the E2-treated group). Similarly, GH administration
      prevented the decrease in cytosolic and nuclear ERs that resulted from
      ovariectomy (119.2 +/- 3.2 fmol/mg protein and 63.4 +/- 1.3 fmol/mg DNA,
      respectively, in the GH-treated group). The Kd of nuclear ER-ligand complex was
      2.0 +/- 0.03 nM in sham-operated rats and was slightly modulated by Ovx, E2 and
      GH (3.3 +/- 0.02, 2.33 +/- 0.09 and 2.23 +/- 0.04 nM, respectively, P < .001),
      but the Kd of cytosolic ER-ligand complex was not altered by Ovx, E2 or GH. Our
      findings indicate that E2 deficiency down-regulates, whereas E2 and GH
      administrations up-regulate intestinal ERs and prevent ovariectomy-induced
      decrease in receptor binding affinity. We conclude that E2 deficiency, E2 and GH
      may modulate intestinal Ca++ absorption, in part, by altering the abundance and
      binding characteristics of intestinal ERs.

PMID- 9655877
TI  - Effects of the abused solvent toluene on recombinant N-methyl-D-aspartate and non
      N-methyl-D-aspartate receptors expressed in Xenopus oocytes.
AB  - Previous studies have shown that toluene, which is commonly abused, depresses
      neuronal activity and causes behavioral effects in both animals and man similar
      to those observed for ethanol. In this study, the oocyte expression system was
      used to test the hypothesis that toluene, like ethanol, inhibits the function of
      ionotropic glutamate receptors. Oocytes were injected with mRNA for specific N
      methyl-D-aspartate (NMDA) or non-NMDA subunits and currents were recorded using
      conventional two-electrode voltage clamp. To enhance the low water solubility of
      toluene, drug solutions were prepared by mixing toluene with alkamuls
      (ethoxylated castor oil) at a 1:1 ratio (v:v) and diluting this mixture to the
      appropriate concentration with barium-containing normal frog Ringer solution.
      Alkamuls, up to 0.1%, had no significant effects on membrane leak currents or on
      NMDA-induced currents. Toluene, up to approximately 9 mM, had only minor effects
      on membrane leak currents but dose-dependently inhibited NMDA-mediated currents
      in oocytes. The inhibition of NMDA receptor currents by toluene was rapid,
      reversible and the potency for toluene's effects was subunit dependent. The
      NR1/2B subunit combination was the most sensitive with an IC50 value for toluene
      induced inhibition of 0.17 mM. The NR1/2A and NR1/2C receptors were 6- and 12
      fold less sensitive with IC50 values of 1.4 and 2.1 mM, respectively. In
      contrast, toluene up to approximately 9 mM did not inhibit kainate-induced
      currents in oocytes expressing GluR1, GluR1(+)R2 or GluR6 subunits. These results
      suggest that some of the effects of toluene on neuronal activity and behavior may
      be mediated by inhibition of NMDA receptors.

PMID- 9655878
TI  - Parathyroid hormone (1-34) increased total body bone mass in aged female rats.
AB  - Daily subcutaneous administration of bovine parathyroid hormone (PTH)(1-34)
      stimulates bone formation and increases bone mass in rat tibiae, femora and
      lumbar spine. However, the effects of PTH on the whole body bone mineral content
      and density determined by dual energy x-ray absortiometry (DEXA) have not been
      previously reported in rats. Eighteen-month-old intact female rats were
      subcutaneously injected daily with 0, 40, 80 or 160 micrograms/kg/day of bovine
      PTH (1-34) for either 15 or 60 days. Whole body DEXA was performed at 1 day
      before autopsy, and bone area, bone mineral content (BMC) and bone mineral
      density (BMD) of the total body were determined. Total femoral, tibial and lumbar
      spine BMD was also determined ex vivo. Cancellous bone histomorphometry was
      performed on sections of double-labeled proximal tibial metaphyses. Whole body
      bone mineral content and density were significantly increased by 60 days, but not
      by 15 days, of PTH treatment at all dose groups compared with vehicle controls.
      Lumbar vertebral and total femoral BMD was significantly increased at all doses
      of PTH by 15 days of administration and further increased by 60 days. All doses
      of PTH increased trabecular bone area in proximal tibial metaphyses by 15 days
      and further increased by 60 days. All doses of PTH increased trabecular bone area
      in proximal tibial metaphyses by 15 days and further increased by 60 days. In
      proximal tibial cancellous bone, dose-dependent increases in percent labeled
      perimeter, mineral apposition rate and bone formation rate-bone volume referent
      were found between 40 and 160 micrograms/kg of PTH treatment by 15 days, and no
      further increases were found by 60 days. Our results showed that in aged female
      rats, bovine PTH(1-34) increased bone formation and total body bone mass.

PMID- 9655879
TI  - Homologous desensitization of the D1A dopamine receptor: efficacy in causing
      desensitization dissociates from both receptor occupancy and functional potency.
AB  - The role of drug efficacy in agonist-induced desensitization was studied in C-6
      glioma cells transfected with the monkey dopamine D1A (mD1A) receptor. Dopamine
      pretreatment for 2 hr produced greater than 80% loss of responsiveness in the
      stimulation of cAMP accumulation that was blocked by the D1 antagonist SCH23390.
      A series of full and partial D1 agonists from structurally dissimilar classes
      were then examined. Three full agonists (dihydrexidine, SKF82958, A77636)
      desensitized the receptor to the same extent as dopamine, whereas two other full
      agonists (dinapsoline and A68930) and all the partial agonists tested (SKF38393,
      pergolide and d-lysergic acid diethylamide tartrate) produced only partial
      desensitization (i.e., 50% that of dopamine). Whereas partial agonists (i.e.,
      SKF38393, pergolide and d-lysergic acid diethylamide tartrate) caused no
      alteration in ligand-accessible mD1A receptors, four of the full agonists
      (dopamine, dihydrexidine, dinapsoline, A68930) caused a 30 to 40% reduction in
      receptor number. One full agonist, A77636, caused nearly an 80% decrease in
      receptor number, despite the fact that the degree of functional desensitization
      was similar to the other full agonists. The desensitization of the D1 receptor
      was homologous, not affecting beta-2 adrenergic receptors endogenous to C-6
      cells. Neither incubation with cAMP analogs, nor inhibition of protein kinase A,
      affected dopamine-induced desensitization, suggesting a cAMP-independent
      mechanism in this cell line. Together, these data suggest that functional
      desensitization of the mD1A receptor expressed in C-6 glioma cells is a cAMP
      independent mechanism, cannot be predicted reliably from agonist efficacy for
      stimulating adenylate cyclase and can occur in the absence of changes in receptor
      number.

PMID- 9655880
TI  - Functional characterization of an organic cation transporter (hOCT1) in a
      transiently transfected human cell line (HeLa).
AB  - Recently, a polyspecific organic cation transporter, hOCT1, was cloned from human
      liver. To date, limited studies examining the functional characteristics of the
      transporter have been performed. The purpose of the present study was to develop
      a mammalian expression system for hOCT1 and to characterize the interactions of
      various compounds with the cloned transporter. Lipofection was used to
      transiently transfect the hOCT1 plasmid DNA in a human cell line, HeLa. We tested
      the interaction of an array of organic cations and other compounds with hOCT1 by
      determining Ki values in inhibiting 14C-tetraethylammonium (TEA) transport in the
      transfected cells. Transient expression of hOCT1 activity was observed between 24
      and 72 hr post-transfection, with maximal expression at approximately 40 hr. TEA
      transport was temperature dependent and saturable with Vmax and K(m) values of
      2.89 +/- 0.448 nmol/mg protein/30 min and 229 +/- 78.4 microM, respectively. 14C
      TEA uptake in hOCT1 plasmid DNA-transfected HeLa cells was trans-stimulated by
      unlabeled TEA and 1-methyl-4-phenyl-pyridinium. Organic cations, including
      clonidine, quinine, quinidine and verapamil (0.1 mM), significantly inhibited 14C
      TEA uptake, whereas the organic anion, p-aminohippuric acid (5 mM), did not. The
      neutral compounds, corticosterone (Ki, 7.0 microM) and midazolam (Ki, 3.7 microM)
      potently inhibited 14C-TEA uptake. The Ki values of several compounds in
      interacting with hOCT1 differed substantially from the corresponding values for
      the rat organic cation transporter, rOCT1, and the human kidney-specific organic
      cation transporter, hOCT2, determined in previous studies. Transiently
      transfected HeLa cells represent a useful tool in studying the interactions and
      kinetics of organic cations and other xenobiotics with hOCT1 and in understanding
      the molecular events involved in organic cation transport.

PMID- 9655881
TI  - Behavioral effects of the delta-selective opioid agonist SNC80 and related
      compounds in rhesus monkeys.
AB  - The behavioral effects of the nonpeptidic delta opioid agonist SNC80 and a series
      of related piperazinyl benzamides derived from the parent compound BW373U86 were
      evaluated in rhesus monkeys. SNC80 (0.1-10 mg/kg) decreased response rates
      maintained by food-reinforcement in a dose- and time-dependent manner, with
      maximal effects occurring within 10 min of intramuscular injection. The potency
      of SNC80 and five other piperazinyl benzamides in this assay of schedule
      controlled responding correlated with their affinity at cloned human delta opioid
      receptors but not with their affinity for cloned human mu receptors. Moreover,
      the effects of SNC80 were selectively antagonized by the delta-selective
      antagonist naltrindole (1.0 mg/kg), but not by the mu selective antagonist
      quadazocine (0.1 mg/kg) or the kappa-selective antagonist norbinaltorphimine (3.2
      mg/kg). These findings indicate that SNC80 functions as a systemically active,
      delta-selective agonist with a rapid onset of action in rhesus monkeys. The
      antinociceptive effects of SNC80 were examined in a warm-water tail-withdrawal
      assay of thermal nociception. SNC80 (0.1-10 mg/kg) produced weak but replicable
      antinociceptive effects that were antagonized by naltrindole (1.0 mg/kg). SNC80
      antinociception was also dose-dependently antagonized by BW373U86 (0.56-1.0
      mg/kg), which was inactive in this procedure. These findings suggest that SNC80
      may have higher efficacy than BW373U86 at delta opioid receptors. Moreover, SNC80
      at doses up to 32 mg/kg did not produce convulsions, which suggests that SNC80
      may also be safer than BW373U86. The effects of SNC80 were also examined in
      monkeys trained to discriminate cocaine (0.4 mg/kg i.m.) or self-administer
      cocaine (0.032 mg/kg/injection,i.v.). In drug discrimination studies, SNC80 (0.1
      10 mg/kg) produced a dose-dependent and naltrindole-reversible increase in
      cocaine-appropriate responding, and complete substitution for cocaine was
      observed in five of seven monkeys tested. However, SNC80 (1.0-100
      micrograms/kg/injection) did not maintain responding in monkeys trained to self
      administer cocaine. Thus, despite its ability to produce cocaine-like
      discriminative stimulus effects, SNC80 may have relatively low abuse potential.

PMID- 9655882
TI  - 3H-naloxone benzoylhydrazone binding in MOR-1-transfected Chinese hamster ovary
      cells: evidence for G-protein-dependent antagonist binding.
AB  - Naloxone benzoylhydrazone (NalBzoH) is a potent mu antagonist in vivo. In a cell
      line stably transfected with MOR-1 (CHO/MOR-1), NalBzoH also was an antagonist
      when examined in adenylyl cyclase studies. In binding studies, it displayed high
      affinity for the mu receptor, confirming its earlier characterization in brain
      membranes. In competition studies under equilibrium conditions, NalBzoH and
      diprenorphine both retained their potency in the presence of the stable GTP
      analog 5'-guanylylimidophosphate, consistent with their mu antagonist properties,
      whereas the agonist DAMGO showed more than a 3-fold loss of affinity. The
      dissociation of 3H-diprenorphine was monophasic. However, kinetic studies
      revealed biphasic dissociations for both 3H-NalBzoH and 3H-DAMGO. The slow
      component of 3H-NalBzoH dissociation, corresponding to the higher affinity state,
      was dependent on coupling to G-proteins. It is selectively abolished by guanine
      nucleotides, leaving only the rapid dissociation phase. Furthermore, the slow
      dissociation component is eliminated by treatment of the cells with pertussis
      toxin, but not cholera toxin. In conclusion, NalBzoH is an unusual opioid.
      Functionally it is an antagonist, a classification consistent with its
      equilibrium binding in the presence of guanine nucleotides. Yet, kinetic studies
      reveal that it labels a G-protein coupled state of the receptor with high
      affinity.

PMID- 9655883
TI  - Characterization of G protein and phospholipase C-coupled agonist binding to the
      Y1 neuropeptide Y receptor in rat brain: sensitivity to G protein activators and
      inhibitors and to inhibitors of phospholipase C.
AB  - Binding of a Y1-subtype-selective agonist of neuropeptide Y (NPY) receptor,
      (Leu31,Pro34)human peptide YY (LP-PYY), to particulates from four rat brain areas
      (parietal cortex area 1, piriform cortex, anterior hypothalamus and hippocampus)
      showed a distinct response to LP-PYY and PYY, a uniformly low sensitivity to
      ligands selective for the Y2, Y4 and Y5 NPY receptor subtypes and high
      sensitivity to a Y1 site-selective antagonist, BIBP-3226. The Y1 binding was
      sensitive to guanine nucleotide-binding protein (G protein) agonist and
      antagonist nucleotides, with the rank order of guanosine 5'-O-(thiotriphosphate)
      (GTP gamma S) > GTP > GDP > guanosine 5'-O-(thiodiphosphate). However, guanine
      nucleotides did not affect about one third of the specific Y1 binding. Most of Y1
      binding could be inhibited by a G protein nucleotide site/docking site receptor
      mimic, mastoparan analog MAS-7. In all areas examined, the Y1 binding of LP-PYY
      was little affected by up to 100 microM of the antagonists of K+, Na+ and Ca++
      channels, protein kinase C, phospholipase A2, phospholipase D and
      phosphatidylinositol 3-kinase, phospholipase substrate phospholipids, steroids or
      detergents. However, the binding was potently inhibited by phospholipase C
      inhibitors (especially the aminosteroid U-73122), which also dissociated the
      bound Y1 ligand in steady-state conditions. U-73122 also displaced the Y1 binding
      insensitive to GTP gamma S. Ligand association with the brain Y1 NPY receptor
      thus strongly depends on activity of both G proteins and phospholipase C,
      implying specific interactions of these transducers/effectors with the receptor
      molecule in ligand binding. A portion of brain Y1 sites could be directly coupled
      to phospholipase(s) C.

PMID- 9655884
TI  - Comparison of tamoxifen effects on the actions of triiodothyronine or growth
      hormone in the ovariectomized-hypothyroid rat.
AB  - Recent studies have suggested that a subset of estrogen responses arise via
      modulation of triiodothyronine (T3) actions, and depend on T3 for expression:
      other estrogen responses are not T3-dependent. Moreover, tamoxifen acts as a full
      estrogen agonist in T3-dependent responses but behaves as an antiestrogen in T3
      independent responses. T3 directly induces a variety of metabolic enzymes and
      proteins, and also induces rat growth hormone (GH). Thus, some T3-dependent
      tamoxifen effects might reflect modulation of GH rather than T3 actions. To
      address this issue, tamoxifen effects on somatotropic and metabolic actions of T3
      and GH were compared in ovariectomized rats with methimazole-induced
      hypothyroidism. Rats were given T3 (10 micrograms/kg/day) or ovine GH (2
      mg/kg/day) with or without tamoxifen (0.5 mg/kg/day) for 30 days. GH was poorly
      effective in producing a sustained increase in somatic growth in hypothyroid rats
      compared to T3; nonetheless, GH effects to increase body weight, tibia length and
      serum insulin-like growth factor I while decreasing fat mass and evoking small
      increases in body temperature were not inhibited by tamoxifen. Tamoxifen also did
      not inhibit GH trends to increase tibia bone mineral density. T3 increased body
      temperature, insulin-like growth factor I levels and all measures of somatic
      growth and, unlike GH, increased food intake and tended to decrease tibia bone
      mineral density. Tamoxifen inhibited the somatotropic actions of T3 (including
      increases in insulin-like growth factor I levels), and produced significant
      increases in tibia bone mineral density only in T3-treated rats. Tamoxifen had no
      effect on T3 actions to increase food intake or body temperature. T3 alone
      increased fat mass and exhibited a tendency to decrease serum triglycerides:
      tamoxifen had no effect on these parameters in the absence of T3. However,
      coadministration of tamoxifen with T3 produced a marked decrease in fat mass and
      increased serum triglycerides. GH had no effect on serum triglycerides in either
      the presence or absence of tamoxifen. Serum glucose levels appeared normal in all
      groups. The data indicate that multiple tamoxifen effects on growth and
      metabolism may reflect modulation of T3 rather than GH actions.

PMID- 9655885
TI  - Angiotensin 1-7 induces bradykinin-mediated relaxation in porcine coronary
      artery.
AB  - Angiotensin 1-7 (Ang 1-7) has been reported to induce relaxation which is
      partially blocked by a kinin receptor antagonist. We investigated the
      relationship between kinins and angiotensin peptides with use of preconstricted
      isolated pig coronary arteries. Ang 1-7 alone (up to 10(-5) M) had no relaxant
      effect. Bradykinin (BK) (10(-10)-10(-7) M) induced transient relaxation,
      returning to basal tone, although BK remained in the bath. In these BK-stimulated
      rings, Ang 1-7 but not BK (both 5 x 10(-6) M) again relaxed the rings by
      approximately 50%. This relaxation was blocked by a BK B2 antagonist, a kininase,
      and a nitric oxide synthase inhibitor. Ang 1-7 inhibited purified angiotensin
      converting enzyme (ACE) by 30 +/- 3.5% (n = 4) at 10(-6) M. However, in BK
      pretreated rings, the ACE inhibitor ramiprilat did not induce relaxation, nor did
      it affect the relaxant response to Ang 1-7, which suggests that the effect of Ang
      1-7 was not caused by ACE inhibition. Ang 1-7-induced vasodilation was reduced by
      69.9 +/- 6.2% by an AT2 receptor blocker, PD-123319, and 29.3 +/- 7.3% by an AT1
      antagonist, losartan. Neither the nonselective AT1/AT2 receptor antagonist
      sarthran nor saralasin inhibited the response to Ang 1-7. Ang II did not elicit
      relaxation either alone or in the presence of losartan, which suggests that
      activation of AT2 receptors does not cause relaxation. Thus, in the presence of
      bradykinin, Ang 1-7 relaxes pig coronary arteries via a PD-123319-sensitive
      mechanism involving nitric oxide, kinins and the BK B2 receptor. The kallikrein
      kinin and renin-angiotensin systems may be linked through the interaction of Ang
      1-7 and BK.

PMID- 9655886
TI  - Pharmacological characterization of an FP prostaglandin receptor on rat vascular
      smooth muscle cells (A7r5) coupled to phosphoinositide turnover and intracellular
      calcium mobilization.
AB  - An FP prostaglandin (PG) receptor on the A7r5 rat aorta smooth muscle cell line
      has been characterized by assays of phosphoinositide (PI) turnover and
      intracellular calcium mobilization stimulated by structurally diverse PGs. In the
      PI turnover assay, cloprostenol was the most potent PG tested, with a potency
      (EC50) of 0.84 +/- 0.06 nM (mean +/- S.E.M., n = 34), and was a full agonist.
      Other known FP receptor agonists tested in this assay had efficacies > or = 85%
      of the cloprostenol value and high potencies: 16-phenoxy PGF2 alpha (2.05 +/-
      0.19 nM), 17-phenyl PGF2 alpha (2.80 +/- 0.59 nM), fluprostenol (4.45 +/- 0.19
      nM), PGF2 alpha (30.9 +/- 2.82 nM) and PhXA85 (43.5 +/- 11.4 nM). Other classes
      of PGs evaluated (PGD2, enprostil, 17-phenyl PGE2, PGE2, sulprostone and U-46619)
      were less potent and less efficacious than the FP receptor agonists, or were
      inactive. For a large group of standard PGs evaluated in the PI turnover assay,
      both potencies and efficacies correlated well with those reported for the FP
      receptor of Swiss mouse 3T3 fibroblasts. The potencies of fluprostenol and PGF2
      alpha as stimuli of intracellular calcium mobilization matched well their
      potencies in the PI turnover assay, but fluprostenol had twice the efficacy of
      PGF2 alpha. Both signaling responses stimulated by fluprostenol were
      significantly inhibited by U73122, a selective inhibitor of phosphoinositide
      turnover (IC50 = 1.25 +/- 0.16 microM for PI turnover), and by chelation of
      calcium in the medium. Together with the PI turnover data, these studies of
      intracellular calcium mobilization linked to activation of the FP receptor,
      provide additional characterization of the pharmacological properties of this
      receptor.

PMID- 9655887
TI  - Novel chemically modified oligonucleotides provide potent inhibition of P
      glycoprotein expression.
AB  - One major form of multiple drug resistance (MDR) to cancer therapeutic agents is
      mediated by overexpression of P-glycoprotein, a membrane ATPase that serves as a
      drug efflux pump. In humans, this protein is the product of the MDR1 gene. We
      have used chemically modified antisense oligonucleotides to reduce expression of
      P-glycoprotein in multidrug-resistant fibroblasts and colon carcinoma cells.
      Although several types of oligonucleotides were tested, compounds having a
      phosphorothioate backbone and a methoxyethoxy (ME) group at the 2' position of
      the ribose ring proved to have the greatest potency. Thus, phosphorothioate 2'-ME
      oligonucleotides directed against either the AUG codon region or the stop codon
      region of the MDR1 message produced substantial (50-70%) inhibition of P
      glycoprotein expression at concentrations of < or = 50 nM. In addition, such
      treatment resulted in augmented drug uptake as measured by flow cytometry.
      Unmodified phosphorothioate compounds of the same sequence were active only in
      the micromolar range. We also tested the ability of several potential delivery
      agents to enhance the pharmacological effectiveness of anti-MDR1
      oligonucleotides. Both commercial Lipofectin, a well known liposomal transfection
      agent, and a liposomal preparation based on a novel "facial amphiphile" were
      effective in enhancing their pharmacological effects of antisense
      oligonucleotides. A Starburst dendrimer, a type of cationic polymer, was also
      effective in oligonucleotide delivery. This report emphasizes that significant
      improvements in antisense pharmacology can be made through judicious use of both
      chemical modifications of oligonucleotides and appropriate delivery systems.

PMID- 9655888
TI  - Blocking of classical complement pathway inhibits endothelial adhesion molecule
      expression and preserves ischemic myocardium from reperfusion injury.
AB  - Myocardial injury after ischemia (I) and reperfusion (R) is related to leukocyte
      activation with subsequent release of cytokines and oxygen-derived free radicals
      as well as complement activation. In our study, the cardioprotective effects of
      exogenous C1 esterase inhibitor (C1 INH) were examined in a rat model of
      myocardial I + R (i.e., 20 min + 24 hr or 48 hr). The C1 INH (10, 50 and 100
      U/kg) administered 2 min before reperfusion significantly attenuated myocardial
      injury after 24 hr of R compared to vehicle treated rats (P < .001). Further,
      cardiac myeloperoxidase activity (i.e., a marker of PMN [polymorphonuclear
      leukocyte] accumulation) in the ischemic area was significantly reduced after C1
      INH treatment compared to vehicle treated animals (0.81 +/- 0.1, 0.34 +/- 0.13,
      0.13 +/- 0.1 vs. 1.44 +/- 0.3 U/100 mg tissue, P < .001). In addition, C1 INH
      (100 U/kg) significantly attenuated myocardial injury and neutrophil infiltration
      even after 48 hr of reperfusion compared to vehicle treatment.
      Immunohistochemical analysis of ischemic-reperfused myocardial tissue
      demonstrated activation of classical complement pathway by deposition of C1q on
      cardiac myocytes and cardiac vessels. In addition, expression of the endothelial
      adhesion molecules P-selectin and intercellular adhesion molecule 1 (ICAM-1) was
      observed after reperfusion of the ischemic myocardium. In this regard, C1 INH
      administration abolished expression of P-selectin and ICAM-1 on the cardiac
      vasculature after myocardial ischemia and reperfusion. Blocking the classical
      complement pathway by exogenous C1 INH appears to be an effective means to
      preserve ischemic myocardium from injury after 24 and 48 hr of reperfusion. The
      mechanisms of this cardioprotective effect appears to be due to blocking of
      complement activation and reduced endothelial adhesion molecule expression with
      subsequent reduced PMN-endothelium interaction, resulting in diminished cardiac
      necrosis.

PMID- 9655889
TI  - The carbohydrate sialyl Lewis(x) (sLe(x)) sulfated glycomimetic GM2941 attenuates
      glucan-induced pulmonary granulomatous vasculitis in the rat.
AB  - We examined the protective effects of GM2941, a sulfated glycomimetic of the
      complex carbohydrate sialyl Lewis(x), in a model of pulmonary granuloma
      development. This study was based on the rationale that formation of glucan
      induced lung granulomas is dependent on neutrophils and that sialyl Lewis(x)
      glycomimetic (GM2941) interferes, in vitro, with P-selectin-dependent neutrophil
      endothelial adhesive interactions. Infusion of particulate yeast cell wall glucan
      into rats results in the rapid (48 hr) formation of monocyte/macrophage-rich
      angiocentric pulmonary granulomas. Development of granulomas exhibits a temporal
      pattern characterized by the early, transient influx of neutrophils into blood
      vessel walls at sites of glucan embolization, followed by accumulation of
      monocytes and macrophages that constitute the definitive angiocentric lesions.
      Within 1 hr after the infusion of glucan, immunohistochemical analysis revealed
      up-regulation of blood vessel wall-associated P-selectin. Previous studies
      utilizing neutrophil-depleted animals have revealed that neutrophils, although
      not present in definitive lesions, are required for full granuloma development.
      The potential of GM2941 to inhibit neutrophil-endothelial cell adhesive
      interactions was demonstrated by the ability of the compound to inhibit P
      selectin-mediated adhesion to histamine-stimulated HUVECs. Infusion of GM2941
      retarded pulmonary granuloma development in a dose-dependent manner. Whole-lung
      myeloperoxidase activity, measured at the time of peak neutrophil accumulation,
      was significantly reduced in animals pretreated with GM2941 (30 mg/kg, 24
      microM/kg), which suggests that this compound affords protection, at least in
      part, through impedance of neutrophil recruitment. These data indicate that
      GM2941 affords a significant degree of protection against granuloma formation
      associated with glucan infusion, probably through the interruption of neutrophil
      recruitment.

PMID- 9655890
TI  - In vivo distribution and metabolism of a phosphorothioate oligonucleotide within
      rat liver after intravenous administration.
AB  - In the rat, the liver represents a major site of phosphorothioate
      oligodeoxynucleotide deposition after i.v. administration. For this reason, we
      examined the intracellular fate of ISIS 1082, a 21-base heterosequence
      phosphorothioate oligodeoxynucleotide, isolated from parenchymal and
      nonparenchymal cell types after systemic dosing using established perfusion and
      separation techniques followed by CGE. Isolated cells were further fractionated
      into nuclear, cytosolic and membrane constituents to assess the intracellular
      localization, distribution and metabolic profiles as a function of time and dose.
      After a 10-mg/kg i.v. bolus, intracellular drug levels where maximal after 8 hr
      and diminished significantly thereafter, suggesting an active efflux mechanism or
      metabolism. Nonparenchymal (i.e., Kupffer and endothelial) cells contained
      approximately 80% of the total organ cellular dose, and this was equivalently
      distributed between the two cell types, while the remaining 20% was associated
      with hepatocytes. Nonparenchymal cells contained abundant nuclear, cytosolic and
      membrane drug levels over a wide dose range. In contrast, at doses of less than
      25 mg/kg, hepatocytes contained significantly less drug with no detectable
      nuclear-association. Doses at or above 25 mg/kg appeared to saturate
      nonparenchymal cell types, whereas hepatocytes continued to accumulate drug in
      all cellular compartments, including the nucleus. Our results suggest that
      although pharmacokinetic parameters vary as a function of hepatic cell type,
      significant intracellular delivery can be readily achieved in the liver after
      systemic administration.

PMID- 9655891
TI  - Characterization of [125I]sauvagine binding to CRH2 receptors: membrane
      homogenate and autoradiographic studies.
AB  - We describe the binding of [125I]tyr(o)sauvagine to membranes of corticotropin
      releasing hormone (CRH2) receptor expressing HEK293/EBNA (293ECRH2 alpha) cells.
      The binding of [125I]tyr(o)sauvagine to CRH2 receptors was temperature, time and
      tissue dependent. Equilibrium was reached in 2 hr at 23 degrees C. Saturation
      data best fit a two-site model with affinity constants of 44 pM and 4.1 nM for
      high and low affinity states, respectively. The high affinity
      [125I]tyr(o)sauvagine binding sites were eliminated with 200 microM Gpp (NH) p,
      indicating coupling to G proteins. The rank order potency of peptide analogs of
      CRH to inhibit [125I]tyr(o)sauvagine binding to CRH2 alpha receptors was:
      urotensin > sauvagine = urocortin > alpha-helical CRH9-41 > rh-CRH >> o-CRH. This
      was in contrast to the rank order potency of the peptides at inhibiting
      [125I]tyr(o)oCRH binding to CRH, receptors: urotensin > urocortin > r/h-CRH > o
      CRH = sauvagine > alpha-helical CRH9-41. We show that two recently identified
      small molecule CRH antagonists with nanomolar potency at the CRH1 receptor, have
      little or no affinity for CRH2 alpha receptors as labeled by
      [125I]tyr(o)sauvagine. Two selective CRH1 receptor antagonists enabled us to
      examine comparative densities of CRH1 and CRH2 receptors in several brain areas.
      We also used [125I]tyr(o)sauvagine in combination with a specific CRH1 antagonist
      to examine the anatomic distribution of CRH2 receptors using receptor
      autoradiography. With a few notable exceptions the CRH2 receptors demonstrated
      autoradiographically in this study match the data obtained by in situ
      hybridization studies on the localization of CRH2 mRNA. The anatomic overlap of
      the autoradiographic and in situ hybridization data suggest that CRH2 receptors
      are postsynaptic. This study demonstrates the utility of using
      [125I]tyr(o)sauvagine to study cloned CRH2 receptors expressed in cell lines. In
      addition, [125I]tyr(o)sauvagine used in conjunction with saturating
      concentrations of a specific CRH1 receptor antagonist allows the study of CRH2
      receptors in brain tissues using both in vitro homogenate binding and receptor
      autoradiography techniques.

PMID- 9655892
TI  - Paracrine endothelin signaling in the control of basal cell proliferation in
      guinea pig tracheal epithelium.
AB  - Immunofluorescent analyses revealed distinct cellular/subcellular localization of
      endothelin (ET) receptors and ET-1 in the epithelial cell layer of guinea pig
      trachea. ETA was expressed predominantly in the basal cells. ETB was expressed
      predominantly in the ciliated columnar cells and was polarized at the apical side
      of the cell body within the cells. Anti-ET-1-immunoreactive cytoplasmic granules
      were contained in the secretory cells that were scattered throughout the
      epithelial layer. Cell proliferation assays with immersion cultures of
      differentially plated cells (basal cell-enriched, non-basal cell-enriched and
      mixed cell cultures) indicated the presence of paracrine ET-1 signaling pathways
      that transmit both positive and negative effects on the basal cell proliferation.
      Direct activation of ETA expressed on the basal cells caused enhancement of their
      growth, whereas that of ETB expressed on the ciliated columnar cells caused
      suppression of the basal cell growth. The latter effect was transmitted by nitric
      oxide whose production was stimulated by ETB activation. Furthermore, blockade of
      either ETA or ETB compromised the epithelial cell layer formation under the air
      interphase culture, which indicates the dependence of tracheal epithelial
      remodeling on a balance between the positive and negative effects of ET-1 on the
      basal cell growth.

PMID- 9655893
TI  - Alteration in regulation of serotonin release in rat dorsal raphe nucleus after
      prolonged exposure to morphine.
AB  - Regulation of serotonin (5-HT) release may be altered during the development of
      opioid tolerance and dependency. To test this hypothesis, changes in
      extracellular 5-HT during prolonged administration of morphine were determined by
      microdialysis in the dorsal raphe nucleus (DRN) of freely behaving rats. Morphine
      or placebo pellets were implanted s.c. As compared to placebo, morphine pellets
      induced a sustained, approximately 50% increase in DRN 5-HT and a significant
      elevation in hot plate latency during the 12-hr period after implantation. One
      week later DRN 5-HT had returned to control levels, and implanting additional
      morphine pellets had no effect on 5-HT or hot plate latency. One day after
      removing the pellets from rats exposed to morphine for 2 wk, acute challenge with
      morphine (20 mg/kg, s.c.) had a significantly smaller effect on 5-HT in the DRN
      as compared to the placebo treatment group. Administration of naltrexone to rats
      implanted with morphine pellets for 2 wk induced signs of withdrawal and a
      significant decrease in DRN 5-HT. These results suggest that the regulation of 5
      HT release is altered during the development of tolerance to morphine. Thus, DRN
      5-HT may be one of the factors involved in the changes in physiology and
      behavioral state during opioid withdrawal.

PMID- 9655894
TI  - Crosstalk between alpha-1A and alpha-1B adrenoceptors in neonatal rat myocardium:
      implications in cardiac hypertrophy.
AB  - The myocardial effect of alpha-1A adrenoceptor (alpha-1 AR) agonists in neonatal
      rats are mediated by alpha-1A AR and not by alpha-1B AR, although both receptor
      subtypes are equally expressed; the functions of alpha-1B AR are not known. Here,
      we report that alpha-1 B ARs inhibit the activities of alpha-1A ARs in neonatal
      rat myocardium so that the inactivation of alpha-1 B ARs by chloroethylclonidine
      (CEC) potentiated the effects of nonselective alpha-1 AR agonist phenylephrine
      (PE) on myocardial protein synthesis and early gene (c-fos and c-jun) expression.
      CEC did not modify the hypertrophic effect of angiotensin II. The potentiation of
      the effects of PE by CEC was associated with a translocation of Ca(++)-dependent
      protein kinase C (PKC)alpha, which did not occur in the absence of CEC. Alpha-1A
      AR-selective agonist A61603 was approximately 1000-fold more potent than PE as a
      positive inotropic agent; it caused the translocation of PKC alpha, which was not
      affected by CEC. 5-Methylurapidil antagonized the effects of PE and A61603,
      suggesting that these were mediated via alpha-1A ARs. Alpha-1D AR antagonist BMY
      7378 did not modify PE-induced translocation of PKC. CEC potentiated the effects
      of PE on Ca++ transients in Fura 2-AM-loaded dispersed cardiomyocytes, and this
      potentiation was prevented by nifedipine. In whole-cell patch-clamp recordings of
      cultured cardiomyocytes, CEC potentiated the effect of norepinephrine on Ca++
      channel currents, which was blocked by 5-methylurapidil. We conclude that alpha
      1A ARs are positively and alpha-1B ARs are negatively coupled to nifedipine
      sensitive Ca++ channels, possibly via Gi protein, and this antagonistic
      relationship between alpha-A AR and alpha-1B AR in the neonatal heart might be
      required physiologically for normal alpha-1 AR-mediated responses and myocardial
      development.

PMID- 9655895
TI  - The role of dopamine D4 receptor in the induction of behavioral sensitization to
      amphetamine and accompanying biochemical and molecular adaptations.
AB  - Our studies examined the role of dopamine D4 receptors in the induction of
      behavioral sensitization to amphetamine (Amp) and accompanying neurochemical and
      molecular adaptive responses using a highly selective D4 antagonist, PNU-101387G.
      Behavioral sensitization to an acute challenge of Amp (2 mg/kg, s.c.) was
      observed in rats pretreated with five daily doses of Amp (2 mg/kg/d, s.c.)
      followed by 7-day withdrawal. Interestingly, coadministration of PNU-101387G with
      Amp during pretreatment completely blocked the sensitized response to an acute
      Amp challenge. The behavioral sensitization and its blockade by the D4 antagonist
      were observed in the absence of significant differences in cerebellar Amp levels
      among the various pretreatment groups. Accompanying behavioral sensitization were
      two postsynaptic neuroadaptive responses: reduction in the ability of Amp to
      induce c-fos gene expression in the infralimbic/ventral prelimbic cortex and NT/N
      mRNA in the accumbal shell. However, concurrent blockade of D4 receptors during
      Amp pretreatment prevented the refractoriness in c-fos and NT/N responsiveness to
      acute Amp. We observed also a presynaptic neuroplastic response associated with
      the behavioral sensitization: a significant augmentation in the ability of Amp to
      increase extracellular dopamine concentrations in the nucleus accumbens shell. As
      with the behavioral sensitization and associated postsynaptic adaptive responses,
      concurrent administration of PNU-101387G with Amp during pretreatment blocked the
      augmentation in Amp-induced dopamine release. Taken together, these data
      demonstrate that dopamine D4 receptors play an important role in the induction of
      behavioral sensitization to Amp and accompanying adaptations in pre- and
      postsynaptic neural systems associated with the mesolimbocortical dopamine
      projections.

PMID- 9655896
TI  - Cocaine administered in vitro to brain slices from rats treated with cocaine
      chronically in vivo results in a gamma-aminobutyric acid receptor-mediated
      hyperpolarization recorded from the dorsolateral septum.
AB  - Previous reports of membrane hyperpolarizations, associated with acute
      application of cocaine, have been recorded from brain slice preparations
      containing aminergic nuclei and have always been attributed to cocaine's ability
      to elevate levels of local biogenic amines followed by activation of their
      receptors. The majority of these studies were conducted with brain slices
      obtained from rats that had not received prior chronic in vivo treatment with
      cocaine. We observed that cocaine alone, at 3 microM, could induce a membrane
      hyperpolarization (COC-HYP) in 100% of rat dorsolateral septal nucleus (DLSN)
      neurons from brain slices of rats treated chronically with cocaine for either 14
      or 28 days in vivo. The DLSN is a nucleus absent of biogenic amine cell bodies,
      but does contain biogenic amine terminals with GABAergic cell bodies and
      terminals. Cocaine applied to brain slices from rats not previously administered
      cocaine or administered cocaine for up to seven days in vivo yielded a maximum
      incidence of COC-HYPs at only 50%. COC-HYPs recorded from DLSN neurons were not
      blocked by previous treatment with amine receptor antagonists or by a TTX and
      zero calcium medium. Based on these results, the ability of DLSN neurons to
      respond to a cocaine challenge with a COC-HYP did not involve inhibition of amine
      reuptake/uptake or action potential release of neuroactive substances. Rather,
      the COC-HYP, with an apparent reversal potential of -80 mV, was reduced by the
      GABA receptor antagonists-bicuculline and CGP-55845A. Lowering extracellular Na+
      or Cl-, lowering of temperature, or previous superfusion with the GABA uptake
      blocker NO-711 could block the COC-HYP. In summary, our data suggest that COC
      HYPs, after application of a cocaine challenge to brain slices from rats treated
      chronically (14-28 days, but not acutely, 7 days) with cocaine are due to cocaine
      induced changes in GABA release and/or transporter function. The latter changes
      in transporter function may involve the reversal of the GABA transporter with
      release of GABA and subsequent activation of postsynaptic GABAA and GABAB
      receptors.

PMID- 9655897
TI  - Effect of N-acetylcysteine on heat shock protein induction by acetaminophen in
      mouse liver.
AB  - It was previously shown that a necrogenic dose of acetaminophen (APAP) induced
      the 25- and 70-kDa heat shock proteins (hsp25 and hsp70i) in mouse liver, whereas
      nonnecrogenic doses failed to alter the level of either hsp. A strong correlation
      between the intralobular sites of APAP arylation of protein and hsp induction
      suggested that APAP-induced protein denaturation may play a role in triggering
      hsp induction. This study was conducted to determine whether APAP arylation of
      protein without concurrent toxicity could cause hsp induction. APAP (250 mg/kg
      i.p.) hepatotoxicity was eliminated using N-acetylcysteine (NAC, 300 mg/kg i.p.)
      or the cytochrome P-450 inhibitor diallyl sulfide (200 mg/kg p.o.). NAC did not
      inhibit APAP arylation of protein when administered 1 or 3 hr after the APAP dose
      but decreased binding by approximately 50% when administered at the same time as
      the APAP dose. Even though APAP hepatotoxicity was blocked by NAC administered 0
      or 1 hr after the APAP dose, NAC did not inhibit the induction of hsp25 or
      hsp70i, indicating that APAP arylation of protein may play a key role in
      triggering hsp induction. Diallyl sulfide blocked APAP arylation of protein,
      hepatotoxicity, and induction of both hsps. These data are consistent with the
      hypothesis that toxicant adduction of protein triggers hsp induction.

PMID- 9655898
TI  - Handling of doxorubicin by the LLC-PK1 kidney epithelial cell line.
AB  - The characteristics of doxorubicin handling have been studied in the cultured
      kidney epithelial cell line LLC-PK1, which has structure and function similar to
      those of renal tubular cells and expresses P-glycoprotein. The uptake of
      doxorubicin by LLC-PK1 cells was time dependent, reaching a steady state at about
      4 hr, and reduced at low temperature; the initial uptake was saturable. The
      efflux of doxorubicin from LLC-PK1 cells was also temperature dependent but, even
      at 37 degrees C, a significant percentage of the drug remained associated with
      the cells after 180 min, which suggests a strong cellular binding, and the
      fluorescence microscopy revealed that the drug was concentrated in intracellular
      organelles. Substances that are substrates for P-glycoprotein, such as verapamil,
      vinblastine, vincristine and quinidine, significantly increased doxorubicin
      concentrations in LLC-PK1 cells. Similar results were obtained with the metabolic
      inhibitors sodium metavanadate and 2,4-dinitrophenol. On the other hand, the
      uptake was not affected by the classic organic cation transport drugs cimetidine,
      decynium 22 or decynium 24, nor by the organic anion drug probenecid. These
      results indicate that, in LLC-PK1 cells, doxorubicin enters by passive diffusion,
      is trapped in intracellular organelles and then is extruded from cells by a
      mechanism that probably involves P-glycoprotein. On the contrary, substances that
      interfere with the renal organic cation or anion secretory system have no effect
      on doxorubicin net accumulation in these cells.

PMID- 9655899
TI  - Long-term beta adrenoceptor-mediated alteration in contractility and expression
      of phospholamban and sarcoplasmic reticulum Ca(++)-ATPase in mammalian ventricle.
AB  - We studied the influence of prolonged administration of the beta adrenoceptor
      agonist isoproterenol on contractile parameters and expression of sarcoplasmic
      reticulum (SR) Ca(++)-ATPase and phospholamban, genes important for Ca++ uptake
      into the SR. Isoproterenol (Iso), 0.9% NaCl (Ctr), propranolol (Prop) or Iso plus
      Prop were administered to rats by subcutaneous infusion with osmotic minipumps
      for 1, 2, 3, 4, 8, 13 and 26 days, respectively. The positive inotropic effect of
      Iso was impaired in rats pretreated with Iso in vivo. Iso pretreatment shortened
      time to peak tension (TPT) by 28%, time of relaxation (RT) by 27% and total
      contraction time (TCT) by 27% compared with the appropriate controls (day 2). The
      shortening of time-dependent contractile indices started after 1 day of Iso
      pretreatment, reached a maximum after 2 days and remained reduced for 4 days.
      Longer treatment by Iso failed to affect time parameters, whereas the positive
      inotropic effect of Iso added to the isolated muscles persisted. The shortened
      contractile time parameters were accompanied by diminished mRNA and protein
      expression of phospholamban (PLB) and SR-Ca(++)-ATPase (SERCA). The mRNA levels
      for PLB and SERCA were maximally reduced by 31 +/- 1.3% and 41 +/- 1.4% in the
      Isopretreated group (2 days) respectively. The reduced mRNA levels were
      accompanied by reduced levels of the corresponding proteins. It is concluded that
      altered levels of PLB and SERCA probably account for the noted changes in
      contractile time parameters in the mammalian heart.

PMID- 9655900
TI  - Lithium protects rat cerebellar granule cells against apoptosis induced by
      anticonvulsants, phenytoin and carbamazepine.
AB  - We have studied the neuroprotective actions of lithium against various insults in
      cultured cerebellar granule cells of rats. The anticonvulsants, phenytoin and
      carbamazepine, have been shown to induce apoptosis of cerebellar granule cells at
      high concentrations. Here we found that co-presence of LiCl (1-10 mM) dose
      dependently protected against phenytoin (20 microM)- and carbamazepine (100
      microM)-induced neuronal apoptosis as assessed by 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyl-tetrazolium bromide metabolism, morphological inspection, chromatin
      condensation and DNA fragmentation. These neuroprotective effects were not
      prevented by inclusion of myoinositol nor mimicked by a potent inositol
      monophosphatase inhibitor, suggestive of a mechanism independent of inositol
      monophosphatase blockade. Lithium also significantly protected against apoptosis
      of cerebellar granule cells induced by aging of the cultures. Additionally,
      lithium suppressed death of cerebellar granule cells exposed to a low
      concentration of extracellular potassium. In contrast, it had no protective
      effect on cell death induced by Ca++ ionophores, a Na+ channel opener, a protein
      kinase inhibitor, a nitric oxide donor or H2O2. Thus, lithium has robust
      neuroprotective effects against apoptotic cell death induced by multiple insults
      with limited selectivity. These actions provide a new avenue to study the
      molecular and cellular mechanisms of this drug.

PMID- 9655901
TI  - Enhanced endocytosis in cultured human breast carcinoma cells and in vivo
      biodistribution in rats of a humanized monoclonal antibody after cationization of
      the protein.
AB  - For monoclonal antibody therapeutics to access target antigen in extravascular
      compartments, an antibody drug delivery technology is required that has the dual
      properties of 1) transendothelial migration of the antibody and 2) endocytosis of
      the antibody into the target cell. These two objectives may be achieved with
      antibody cationization, and the present studies examine the feasibility of
      cationizing the humanized 4D5 monoclonal antibody directed against the p185HER2
      oncogenic protein. The cationized antibody binds to the p185HER2 extracellular
      domain with an ED50 of 35 micrograms/ml and inhibits SK-BR3 cell proliferation
      similar to the native antibody. Confocal microscopy showed that although there
      was binding of the native 4D5 antibody to the plasma membrane of SK-BR3 cells,
      this antibody was confined to the periplasma membrane space with minimal
      endocytosis into the cell. In contrast, robust internalization of the cationized
      4D5 antibody by the SK-BR3 cells was demonstrated by confocal microscopy. The
      systemic volume of distribution of the cationized 4D5 antibody was 11-fold
      greater than that of the native antibody. In summary, these studies show that a
      humanized monoclonal antibody may be cationized with retention of antibody
      affinity for the target antigen and biological activity, yet with a marked
      alteration in the cellular distribution and pharmacokinetics in vivo.

PMID- 9655902
TI  - Expression of estrogen sulfotransferase in MCF-7 cells by cDNA transfection
      suppresses the estrogen response: potential role of the enzyme in regulating
      estrogen-dependent growth of breast epithelial cells.
AB  - Estrogen sulfotransferase (EST) is a cytosolic enzyme that catalyzes the
      sulfonation of estrogens at the 3-hydroxyl position by use of 3'-phosphoadenosine
      5'-phosphosulfate as an activated sulfate donor. Although largely known and
      studied as a phase II metabolic enzyme with prominent expression in the liver,
      the high substrate specificity of EST (with a high Vmax/Km value for estrogen)
      suggests that expression of the enzyme in extrahepatic, estrogen target tissues,
      such as the breast epithelium, may constitute an effective mechanism for local
      estrogen regulation as well. In this study, we have evaluated the physiological
      significance of EST expression by cDNA transfection studies with use of the
      estrogen-dependent MCF-7 breast cancer cell line as a model system. We show that
      expression of EST in MCF-7 cells effectively reduces the cells' response to
      physiological concentrations of estradiol (10 nM) by up to 70% as determined in
      an estrogen-responsive reporter gene assay. In addition, we demonstrate that
      expression of EST similarly inhibits estrogen-stimulated DNA synthesis and cell
      proliferation by 21% and 46%, respectively. (The thymidine incorporation rate was
      measured 3 days after and the cell numbers were counted 8 days after
      transfection.) These results provide direct evidence for the functional
      significance of in situ EST expression in the breast epithelium and suggest that
      abnormal regulation of the enzyme may have pathological implications in the
      development and maintenance of hormone-dependent breast carcinomas.

PMID- 9655903
TI  - An investigation of the relationship between estrogen, estrogen metabolites and
      blood cholesterol levels in ovariectomized rats.
AB  - 17 beta-Estradiol (E2) has long been known for protecting against coronary heart
      disease by lowering cholesterol levels in premenopausal women. A recent study in
      our laboratory suggested that two hydroxylated metabolites of E2 possess similar
      hypocholesterolemic effects in male rats. This effect has been further
      investigated with additional estrogen metabolites in ovariectomized rats with a
      view toward mimicking the true postmenopausal situation in humans. Their effects
      in reproductive tissues were also evaluated histologically. Fundamentally, the
      following issues were addressed: (1) Do oxidized metabolites of estradiol lower
      total cholesterol levels? (2) Can a hypocholesterolemic effect be achieved
      without eliciting estrogenic activities on reproductive tissues? The results of
      this investigation showed that a number of oxygenated metabolites of estradiol
      can lower cholesterol levels. Among them, 4-hydroxyestradiol (4-OHE2) produced a
      striking hypocholesterolemic effect and a substantial uterotropic effect. 2
      Hydroxyestradiol (2-OHE2), 2-methoxyestradiol (2-meoE2) and 2-methoxyestrone (2
      meoE1) produced a significant decrease in cholesterol levels at doses that did
      not produce significant uterotropic effects.

PMID- 9655905
TI  - Identification of a new metabolite of CPT-11 (irinotecan): pharmacological
      properties and activation to SN-38.
AB  - Irinotecan, or CPT-11 (7-ethyl-10-[4-(1-piperidino)-1
      piperidino]carbonyloxycamptothecine++ +), is a water-soluble derivative of
      camptothecine with promising activity against several types of malignancies. In
      addition to 7-ethyl-10-hydroxycamptothecine (SN-38), its active metabolite, we
      were able to identify several metabolites in the plasma of patients treated with
      this drug, especially an oxidative metabolite, 7-ethyl-10[4-N-(5-aminopentanoic
      acid)-1-piperidino] carbonyloxy-camptothecine. During our study of the
      biosynthesis of 7-ethyl-10[4-N-(5-aminopentanoic acid)-1-piperidino] carbonyloxy
      camptothecine from CPT-11 by human liver microsomes, we were able to detect
      another quantitatively important polar metabolite, which was also present in the
      plasma and urine of patients treated with CPT-11. On the basis of preliminary
      experiments, the structure of this compound was postulated to be 7-ethyl-10-(4
      amino-1-piperidino)carbonyloxycamptothecine, and this structure was synthesized
      by Rhone-Poulenc Rorer. Urine samples and human liver microsomal extracts were
      studied by high-performance liquid chromatography/atmospheric pressure chemical
      ionization/tandem mass spectrometry to identify its structure formally. The
      identification of the metabolite was supported by identical retention time, mass
      to-charge ratio and tandem mass spectrometry fragmentation as a synthetic
      standard. Like irinotecan, 7-ethyl-10-(4-amino-1-piperidino)
      carbonyloxycamptothecine was a weak inhibitor of cell growth of P388 cells in
      culture (IC50 = 3.4 micrograms/ml vs. 2.8 micrograms/ml for irinotecan and 0.001
      microgram/ml for SN-38). It was also a poor inducer of topoisomerase I-DNA
      cleavable complexes (100-fold less potent than SN-38). However, unlike 7-ethyl
      10[4-N-(5-aminopentanoic acid)-1-piperidino] carbonyloxy-camptothecine, this new
      metabolite could be hydrolyzed to SN-38 by human liver microsomes and purified
      human liver carboxylesterase, though to a lesser extent than irinotecan. This
      compound can therefore contribute to the activity and toxicity profile of
      irinotecan in vivo.

PMID- 9655904
TI  - In vitro biological characterization and antiangiogenic effects of PD 166866, a
      selective inhibitor of the FGF-1 receptor tyrosine kinase.
AB  - Through direct synthetic efforts, we discovered a small molecule that is a
      nanomolar inhibitor of the human fibroblast growth factor-1 receptor (FGFR)
      tyrosine kinase. PD 166866, a member of a new structural class of tyrosine kinase
      inhibitors, the 6-aryl-pyrido[2,3-d]pyrimidines, was identified by screening a
      compound library with assays that measure protein tyrosine kinase activity. PD
      166866 inhibited human full-length FGFR-1 tyrosine kinase with an IC50 value of
      52.4 +/- 0.1 nM and was further characterized as an ATP competitive inhibitor of
      the FGFR-1. In contrast, PD 166866 had no effect on c-Src, platelet-derived
      growth factor receptor-beta, epidermal growth factor receptor or insulin receptor
      tyrosine kinases or on mitogen-activated protein kinase, protein kinase C and
      CDK4 at concentrations as high as 50 microM. PD 166866 was a potent inhibitor of
      basic fibroblast growth factor (bFGF)-mediated receptor autophosphorylation in
      NIH 3T3 cells expressing endogenous FGFR-1 and in L6 cells overexpressing the
      human FGFR-1 tyrosine kinase, confirming a tyrosine kinase-mediated mechanism. PD
      166866 also inhibited bFGF-induced tyrosine phosphorylation of the 44- and 42-kDa
      (ERK 1/2) mitogen-activated protein kinase isoforms in L6 cells, presumably via
      inhibition of bFGF-stimulated FGFR-1 tyrosine kinase activation. PD 166866 did
      not inhibit platelet-derived growth factor, epidermal growth factor or insulin
      stimulated receptor autophosphorylation in vascular smooth muscle, A431 or NIHIR
      cells, respectively, further supporting its specificity for the FGFR-1. In
      addition, daily exposure of PD 166866 to L6 cells at concentrations from 1 to 100
      nM resulted in a concentration-related inhibition of bFGF-stimulated cell growth
      for 8 consecutive days with an IC50 value of 24 nM. In contrast, PD 166866 had
      little effect on platelet-derived growth factor-BB-stimulated growth of L6 cells
      or serum-stimulated vascular smooth muscle cell proliferation. Finally, PD 166866
      was found to be a potent inhibitor of microvessel outgrowth (angiogenesis) from
      cultured artery fragments of human placenta. These results highlight the
      discovery of PD 166866, a new nanomolar potent and selective small molecule
      inhibitor of the FGFR-1 tyrosine kinase with potential use as
      antiproliferative/antiangiogenic agent for such therapeutic targets as tumor
      growth and neovascularization of atherosclerotic plaques.

PMID- 9655906
TI  - Sixty years of thiamin diphosphate biochemistry.
AB  - The mechanism of ThDP enzymes originates in the anionic (ylid) structure of the
      coenzyme. On the other hand, no ylid species (as permanently existing structure)
      could be detected by 13C2-NMR studies with PDC (yeast), when the cofactor binds
      to the active site. Therefore, the rate of ylid formation as the first step of
      the catalytic mechanism distinguishes decisively the power (kcat) of all ThDP
      enzymes. 2H/1H-exchange experiments with PDC, TK, PDH and POX have shown that
      within the active center of ThDP enzymes (under native pH conditions!) the
      aminopyrimidine part generates the essential ylid structure by enhancing the
      dissociation rate (acidity) of the C2-H bond up to 4-6 orders of magnitude.
      Moreover, it could be proved that the mechanism of substrate activation of PDC
      (yeast) is also connected directly with the C2-H activation by the
      aminopyrimidine part. Experiments with analogs of ThDP or modified apoenzymes
      (via site-directed mutagenesis) have shown that this mechanism requires as
      essential elements a hydrogen bond between the pyrimidine N1' atom and a
      conserved Glu side chain of the different apoenzymes as well as the (evolutionary
      conserved) V-conformation. The latter positions the 4'-amino group in direct
      (functional) contact to the C2-H bond. A proposal is discussed, how the 4'
      positioned amino group in cooperation with the N1' atom could increase the C2-H
      dissociation rate.

PMID- 9655907
TI  - Transition-state theoretical interpretation of the catalytic power of pyruvate
      decarboxylases: the roles of static and dynamical considerations.
AB  - The catalytic power of two thiamin diphosphate (ThDP)-dependent enzymes, yeast
      pyruvate decarboxylase (the hysteretically regulated enzyme from Saccharomyces
      cerevisiae, SCPDC) and bacterial pyruvate decarboxylase (the unregulated enzyme
      from Zymomonas mobilis, ZMPDC), are analyzed by thorough-going application of
      transition-state theory, i.e. by a static approach that emphasizes the state
      function character of the free energy of activation and takes no explicit account
      of dynamical considerations. The overall catalytic reaction is resolved into
      manifolds for addition (conversion of free enzyme and substrate to the complex of
      enzyme with the pyruvate:ThDP adduct), decarboxylation, and elimination
      (conversion of the complex of enzyme with the acetaldehyde:ThDP adduct formed by
      decarboxylation into free product and free enzyme). For SCPDC, the addition
      manifold is most strongly catalyzed (3x1012-fold, corresponding to net transition
      state stabilization of 72 kJ/mol, transition-state stabilization of 83 kJ/mol
      diminished by reactant-state stabilization of 11 kJ/mol), the decarboxylation
      manifold is least strongly catalyzed (5x107-fold, corresponding to net transition
      state stabilization of 41 kJ/mol, transition-state stabilization of 68 kJ/mol
      diminished by reactant-state stabilization of 27 kJ/mol), and the elimination
      manifold is catalyzed to an intermediate degree (2x1010-fold, corresponding to
      net transition-state stabilization of 59 kJ/mol, transition-state stabilization
      of 76 kJ/mol diminished by reactant-state stabilization of 17 kJ/mol). A similar
      situation holds for ZMPDC. There is no need to make an explicit analysis of
      dynamical factors in order to describe the catalytic mechanism and catalytic
      power of these complex enzymes.

PMID- 9655908
TI  - Thiamin metabolism and thiamin diphosphate-dependent enzymes in the yeast
      Saccharomyces cerevisiae: genetic regulation.
AB  - The yeast Saccharomyces cerevisiae utilises external thiamin for the production
      of thiamin diphosphate (ThDP) or can synthesise the cofactor itself. Prior to
      uptake into the cell thiamin phosphates are first hydrolysed and thiamin is taken
      up as free vitamin which is then pyrophosphorylated by a pyrophosphokinase.
      Synthesis of ThDP starts with the production of hydroxyethylthiazole and
      hydroxymethylpyrimidine. Those are linked to yield thiamin phosphate which is
      hydrolysed to thiamin and subsequently pyrophosphorylated. The THI genes encoding
      the enzymes of these final steps of ThDP production and of thiamin utilisation
      have been identified. Their expression is controlled by the level of thiamin and
      a number of regulatory proteins involved in regulated expression of the THI genes
      are known. However, the molecular details of the regulatory circuits need to be
      deciphered. Since the nucleotide sequence of the entire yeast genome is known we
      can predict the number of ThDP-dependent enzymes in S. cerevisiae. Eleven such
      proteins have been found: pyruvate decarboxylase (Pdc, three isoforms),
      acetolactate synthase, a putative alpha-ketoisocaproate decarboxylase with a
      regulatory role in ThDP synthesis and two proteins of unknown function form the
      group of Pdc related enzymes. In addition there are two isoforms for
      transketolase as well as the E1 subunits of pyruvate dehydrogenase and 2
      oxoglutarate dehydrogenase. Expression of most of these genes is either induced
      or repressed by glucose. Surprisingly, it has been found recently that expression
      of one of the genes for Pdc is repressed by thiamin. In addition, the regulatory
      protein Pdc2p was shown to be required for high level expression of both the THI
      and the PDC genes. Apparently, the production of ThDP and of the enzymes using
      this cofactor is coordinately regulated. Future research will focus on the
      elucidation of the molecular mechanisms of this novel type of regulation.

PMID- 9655909
TI  - Activation of thiamin diphosphate in enzymes.
AB  - Activation of the coenzyme ThDP was studied by measuring the kinetics of
      deprotonation at the C2 carbon of thiamin diphosphate in the enzymes pyruvate
      decarboxylase, transketolase, pyruvate dehydrogenase complex, pyruvate oxidase,
      in site-specific mutant enzymes and in enzyme complexes containing coenzyme
      analogues by proton/deuterium exchange detected by 1H-NMR spectroscopy. The
      respective deprotonation rate constant is above the catalytic constant in all
      enzymes investigated. The fast deprotonation requires the presence of an
      activator in pyruvate decarboxylase from yeast, showing the allosteric regulation
      of this enzyme to be accomplished by an increase in the C2-H dissociation rate of
      the enzyme-bound thiamin diphosphate. The data of the thiamin diphosphate
      analogues and of the mutant enzymes show the N1' atom and the 4'-NH2 group to be
      essential for the activation of the coenzyme and a conserved glutamate involved
      in the proton abstraction mechanism of the enzyme-bound thiamin diphosphate.

PMID- 9655910
TI  - Structure and expression of an asparaginyl-tRNA synthetase gene located on
      chromosome IV of Arabidopsis thaliana and adjacent to a novel gene of 15 exons.
AB  - The gene AtNS1 coding for an asparaginyl-tRNA synthetase and located on
      chromosome IV of Arabidopsis thaliana has been characterized. AtNS1 is the first
      asparaginyl-tRNA synthetase gene described in higher plants. The genomic
      environment of AtNS1 has been studied, as well as a partial cDNA of a second
      homologous asparaginyl-tRNA synthetase gene, AtNS2. Both AtNS1 and AtNS2 exhibit
      the highest similarity with prokaryotic homologues. A large novel gene of 15
      exons, named AtG2484-1, is located adjacent to AtNS1. AtG2484-1 shows features
      rarely described in plants including large exons and one 3' non-coding exon. PCR
      and Northern analyses were carried out to obtain information about the expression
      of these genes in various A. thaliana tissues.

PMID- 9655911
TI  - Thiamin-dependent enzymes as catalysts in chemoenzymatic syntheses.
AB  - Enzymes are increasingly being used to perform regio- and enantioselective
      reactions in chemoenzymatic syntheses. To utilize enzymes for unphysiological
      reactions and to yield novel products, a broad substrate spectrum is desirable.
      Thiamin diphosphate (ThDP)-dependent enzymes vary in their substrate tolerance
      from rather strict substrate specificity (phosphoketolases, glyoxylate
      carboligase) to more permissive enzymes (transketolase, dihydroxyacetone
      synthase, pyruvate decarboxylase) and therefore differ in their potential to be
      used as biocatalysts. We give an overview of the known substrate spectra of ThDP
      dependent enzymes and present examples of multi-enzyme or chemoenzymatic
      approaches which involve ThDP-dependent enzymes as biocatalysts to obtain
      pharmaceutical compounds as ephedrine and glycosidase inhibitors, sex pheromones
      as exo-brevicomin, 13C-labeled metabolites, and other intermediates as 1
      deoxyxylulose 5-phosphate, a precursor of vitamins and isoprenoids.

PMID- 9655912
TI  - Expression of murine H1 histone genes during postnatal development.
AB  - Murine genes encoding the seven H1 histone isoforms H1.1-H1.5, H1(o) and H1t have
      been isolated and sequenced. We have established expression patterns of these
      genes in several tissues during postnatal development. For that analysis, RNase
      protection assay rather than Northern blot hybridization was used, since the
      sequences of these genes are highly similar and would cross-hybridize under
      Northern blot conditions. Expression patterns of H1.1 to H1.5 and H1(o) were
      determined in tissues of animals at days 5, 9 and 20 after birth and of adult
      mice. In addition, RNA was analyzed in three mouse cell lines (NIH3T3, P19, TM4).
      Transcription of the subtype genes H1.2 and H1.4 was found in all tissues and
      cell lines studied. The most varied expression patterns were obtained with the
      H1.1 subtype. H1.1 mRNA was found at high concentrations in thymus and spleen
      throughout development and in testis beginning with a low expression in 5-day-old
      animals and increasing levels in testis RNA from 9- and 20-day-old and adult
      mice. H1(o) mRNA was found primarily in highly differentiated tissues with
      concentrations decreasing from 5-day-old to adult animals.

PMID- 9655913
TI  - Identification and sequencing of a cytochrome P450 gene cluster from
      Bradyrhizobium japonicum.
AB  - Sequencing of a region from Bradyrhizobium japonicum previously shown to encode
      for cytochromes P450 revealed a cluster of three complete P450 genes (CYP112,
      CYP114, and CYP117) plus a partial P450 gene fragment (CYP115P). Present also are
      five additional open reading frames. The close positioning of the genes suggests
      that they comprise an operon. Although the biochemical function of the gene
      products is uncertain, the similarities to other genes suggests an operon
      involved in terpenoid synthesis. ORF3 has similarity to a [3Fe-4S] ferredoxin
      from Streptomyces griseolus. ORF4 has strong similarity to members of the short
      chain alcohol dehydrogenase family, including sterol dehydrogenases from enteric
      bacteria and to some plant 3-oxoacyl-(acyl carrier protein) reductases. ORF6 has
      strong similarity to prenyl transferases, including dimethylallyltranstransferase
      from Escherichia coli. ORF7 bears some similarity to plant genes for ent-kaurene
      synthase (a precursor of gibberellins), and to bacterial squalene-hopene
      cyclases. ORF8 has some similarity to a Streptomyces gene for synthesis of the
      cyclic sesquiterpene pentalenene. The 5' end of the mRNA transcript is 38-39
      nucleotides downstream from the center of a motif that bears sequence homology to
      bacterial fnr promoters. A gus operon fusion to the promoter was expressed
      anaerobically and symbiotically 6-10-fold greater than aerobically.

PMID- 9655914
TI  - Theoretical studies on the electronic and energetic properties of the
      aminopyrimidine part of thiamin diphosphate.
AB  - Ab initio calculations on the HF-SCF 6-31g* level were performed on tautomers as
      well as protonated and deprotonated species of thiamin. Aspects of the proton
      relay function of the 4'-aminopyrimidine ring in the thiamin catalysis were
      studied on model systems. The acidity of the 4'-amino group increases in the N1'
      and N3' protonated thiamin systems. Starting from the 4'N deprotonated thiamin,
      the calculated reaction coordinate of the ylide formation suggests the
      cocatalytic function of the 4'-amino/imino group. Some structural, energetic, and
      electronic properties of the model systems are discussed with respect to key
      steps in the catalytic mechanism.

PMID- 9655915
TI  - Structure-function relationships and flexible tetramer assembly in pyruvate
      decarboxylase revealed by analysis of crystal structures.
AB  - The crystal structures of pyruvate decarboxylase from the yeast Saccharomyces
      uvarum and Saccharomyces cerevisiae have been determined at 2.4 and 2.3 A
      resolution, respectively. These structures provide details about the protein fold
      and domain assembly within subunits, about subunit assembly to form dimers and
      about dimer assembly to form tetramers. They also provide a clear picture of the
      active site centered on the thiamin diphosphate cofactor, and have allowed amino
      acids critical for catalysis and involved in stabilization of the unusual
      cofactor conformation to be identified. The structural information has enabled
      identification of the site of allosteric activation to be centered on Cys-221,
      and suggests that a six residue segment leading from the regulatory site to the
      catalytic site may be involved in transmission of a binding signal. The
      importance of several amino acids within this segment in the regulatory process,
      as well as some involved in stabilizing and activating the cofactor has been
      confirmed by analyzing the behavior of recombinant enzymes with single point
      mutations introduced at these sites. Additional structures have been determined
      for pyruvate decarboxylase in multiple crystal forms, some of which were obtained
      from crystals grown with known allosteric activators present in the media.
      Currently four distinct types of tetramers have been observed, with each showing
      a different mode of association of dimers to form the tetramers. In some of the
      cases involving the presence of allosteric activators drastic changes in the mode
      of dimer assembly to form tetramers is seen.

PMID- 9655916
TI  - Differential requirements for basic amino acids in transcription factor IIIA-5S
      gene interaction.
AB  - Basic amino acids Arg, Lys, and His in the Cys2His2 zinc fingers of transcription
      factor IIIA (TFIIIA) potentially have important roles in factor binding to the
      extended internal control region (ICR) of the 5S ribosomal gene. Conserved and
      non-conserved basic residues in the N-terminal fingers I, II, III and the more C
      terminal fingers V and IX were analyzed by site-directed mutagenesis and DNase I
      protection in order to assess their individual requirement in the DNA-binding
      mechanism. In the DNA recognition helix of finger II, the conserved Arg at
      position 62 (N-terminal side of the first zinc-coordinating histidine) was
      changed to a Leu or Gln. Both the R62L and R62Q mutations inhibited Xenopus
      TFIIIA-dependent DNase I footprinting along the entire 5S gene ICR. When His-58
      (non-conserved basic residue with DNA-binding potential in the same helical
      region) was changed to a Gln, the mutated protein was able to protect the ICR
      from DNase I digestion. Therefore, Arg-62 is individually required for TFIIIA
      binding over the entire ICR whereas His-58 is not. Fingers V and IX have
      conserved Arg residues in positions identical to Arg-62 in finger II (Arg-154 in
      finger V and Arg-271 in finger IX). When these residues were changed to Leu and
      Ile respectively, TFIIIA-dependent DNase I protection was observed along the
      entire 5S gene ICR. These results indicate differing DNA-binding mechanisms by
      the N-terminal fingers versus the C-terminal fingers at the level of individual
      amino acid-nucleotide interactions. In the N-terminal finger I, the conserved Lys
      at position 11 outside the recognition helix and a conserved hydrophobic Trp at
      position 28 within the helix were changed to an Ala and Ser respectively. The
      K11A change inhibited TFIIIA-dependent DNase I protection to a much greater
      extent than the W28S change.

PMID- 9655917
TI  - Cloning and sequencing of the cDNA for an RNA-binding protein from the Mexican
      axolotl: binding affinity of the in vitro synthesized protein.
AB  - A full length cDNA for an RNA-binding protein (axolotl RBP) with consensus
      sequence (RNP-CS) from the Mexican axolotl, Ambystoma mexicanum, has been cloned
      from a subtraction library. In vitro translation with synthetic mRNA and
      subsequent hybrid-arrested translation with a specific antisense oligonucleotide
      confirms that the axolotl RBP cDNA encodes an approx. 16 kDa polypeptide.
      Computer-assisted analyses revealed amino acid similarities of 58-60% to various
      RNA-binding proteins and a 90 amino acid region at the amino-terminal end
      constituting the putative RNA-binding domain (RNP-CS) with two highly conserved
      motifs, RNP2 and RNP1. Phylogenetic analysis suggests that the putative RNA
      binding protein from axolotl is unique. A binding assay with radiolabeled axolotl
      RBP showed that this RNA-binding protein bound strongly with poly(A) and to a
      lesser degree with poly(U), but not at all with poly(G), poly(C), or DNA.

PMID- 9655918
TI  - Subunit structure, function and organisation of pyruvate decarboxylases from
      various organisms.
AB  - The nature of the environment of macromolecules influences and determines the
      state of their overall structure and the extent of binding of specific
      (cofactors, substrates) or unspecific ligands. How these interactions between
      enzyme molecules and ligands influence their quaternary structures and, in this
      way, the realisation of high catalytic activity will be discussed here for the
      enzyme pyruvate decarboxylase from various organisms: brewer's yeast, brewer's
      yeast strain, recombinant wild type and site-specific mutants of Saccharomyces
      cerevisiae, the recombinant wild type of the bacterium Zymomonas mobilis and
      germinating seeds of the plant Pisum sativum from a structural point of view
      including both high resolution models from crystal structure analysis and low
      resolution models from small angle X-ray solution scattering with synchrotron
      radiation.

PMID- 9655919
TI  - Superinduction of interleukin-6 mRNA in lung epithelial H292 cells depends on
      transiently increased C/EBP activity and durable increased mRNA stability.
AB  - Restriction of eukaryotic protein synthesis affects the regulation of some
      transiently expressed gene transcripts resulting in their superinduction. We
      determined the transcriptional and post-transcriptional processes implicated in
      IL-6 mRNA superinduction in a human lung-derived epithelial cell line H292, and
      their kinetics in the absence and presence of an exogenous stimulus, tumor
      necrosis factor-alpha (TNF-alpha). Cycloheximide (CHI) at 10 microg/ml, which
      inhibited protein synthesis for 80%, caused a 80-fold induction of IL-6 mRNA
      level which was due predominantly to a stabilization of IL-6 mRNA (20-fold) early
      on. Employing transient transfection protocols we noted a small positive effect
      of CHI on transcription, mediated by the proximal and the distal C/EBP sites of
      the IL-6 promoter and paralleled by an increased C/EBP DNA-binding activity,
      similar to that found for exposure to TNF-alpha alone. TNF-alpha and CHI
      synergized on IL-6 mRNA expression (200-fold increase) which was due to an
      increased transcription, corresponding to a further increased C/EBP DNA-binding
      activity. However, the effect of CHI on IL-6 gene transcription was transient, in
      support of the need for ongoing protein synthesis for C/EBP activity. These
      findings indicate that IL-6 mRNA superinduction, at least in H292 cells, is
      regulated predominantly by modulating the repressive system that ensures a rapid
      degradation of IL-6 mRNA.

PMID- 9655920
TI  - 1,25-Dihydroxyvitamin D3 inhibition of col1a1 promoter expression in calvariae
      from neonatal transgenic mice.
AB  - We studied the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on organ cultures
      of transgenic mouse calvariae containing segments of the Col1a1 promoter
      extending to -3518, -2297, -1997, -1794, -1763, and -1719 bp upstream of the
      transcription start site fused to the chloramphenicol acetyltransferase (CAT)
      reporter gene. 1,25(OH)2D3 had a dose-dependent inhibitory effect on the
      expression of the -3518 bp promoter construct (ColCAT3.6), with maximal
      inhibition of about 50% at 10 nM. This level of inhibition was consistent with
      the previously observed effect on the endogenous Col1a1 gene in bone cell models.
      All of the shorter constructs were also inhibited by 10 nM 1,25(OH)2D3,
      suggesting that the sequences required for 1, 25(OH)2D3 inhibition are downstream
      of -1719 bp. The inhibitory effect of 1,25(OH)2D3 on transgene mRNA was
      maintained in the presence of the protein synthesis inhibitor cycloheximide,
      suggesting that the inhibitory effect on Col1a1 gene transcription does not
      require de novo protein synthesis. We also examined the in vivo effect of
      1,25(OH)2D3 treatment of transgenic mice on ColCAT activity, and found that 48 h
      treatment caused a dose-dependent inhibition of CAT activity in calvariae
      comparable to that observed in organ cultures. In conclusion, we demonstrated
      that 1,25(OH)2D3 inhibits Col1A1 promoter activity in transgenic mouse calvariae,
      both in vivo and in vitro. The results indicate that there is a 1, 25(OH)2D3
      responsive element downstream of -1719 bp. The inhibitory effect does not require
      new protein synthesis.

PMID- 9655921
TI  - Regulation of thiamin diphosphate-dependent 2-oxo acid decarboxylases by
      substrate and thiamin diphosphate.Mg(II) - evidence for tertiary and quaternary
      interactions.
AB  - The regulatory mechanism of substrate activation in yeast pyruvate decarboxylase
      is triggered by the interaction of pyruvic acid with C221 located on the beta
      domain at >20 A from the thiamin diphosphate (ThDP). To trace the putative
      information transfer pathway, substitutions were made at H92 on the alpha domain,
      across the domain divide from C221, at E91, next to H92 and hydrogen bonded to
      W412, the latter being intimately involved in the coenzyme binding locus.
      Additional substitutions were made at D28, E51, H114, H115, I415 and E477, all
      near the active center. The pH-dependent steady-state kinetic parameters,
      including the Hill coefficient, provide useful insight to this effort. In
      addition to C221, the residues H92, E91, E51 and H114 and H115 together appear to
      have a critical impact on the Hill coefficient, providing a pathway for
      information transfer. To study the activation by ThDP.Mg(II), variants at G231
      (of the conserved GDG triplet) and at N258 and C259 (all three being part of the
      putative ThDP fold) of the E1 component of the Escherichia coli pyruvate
      dehydrogenase multienzyme complex were studied. Kinetic and spectroscopic
      evidence suggests that the Mg(II) ligands are very important to activation of the
      enzymes by cofactors.

PMID- 9655922
TI  - Identification of heavy metal induced changes in the expression patterns of the
      translationally controlled tumour protein (TCTP) in the earthworm Lumbricus
      rubellus1.
AB  - Heavy metal contaminated soils are assessed for specific human health and
      ecological risk by governmental regulatory agencies utilizing the abundant soil
      invertebrate, the earthworm, in a biomonitoring process. Fingerprinting the
      molecular genetic responses resulting from heavy metal exposure facilitates the
      identification of biomarkers for assessing the impact of such pollution on
      individual organisms. This paper reports the identification of a novel
      translationally controlled tumour protein (TCTP) in the earthworm Lumbricus
      rubellus. In addition to the standard molecular biological technique of
      differential Southern blotting, a fully quantitative approach (fluorescent
      microvolume PCR) was performed to assess the specific expression profiles of TCTP
      in earthworms exposed to different heavy metal regimes. After normalizing with
      actin as an invariant control, the results showed that TCTP was upregulated by at
      least a factor of 4 in the population originating from a Pb/Zn/Cd polluted mine,
      compared to an unpolluted control population. An even more pronounced increase
      was identified in earthworms native to a Cu polluted mine, where TCTP increased
      335-fold. TCTP copies in earthworms exposed to artificial soil with a single
      stressor (Cd) were 14 times higher than in the appropriate control earthworms
      (maintained on artificial soil without Cd). The data presented are novel in two
      ways: first, they provide evidence for an upregulation that is induced by heavy
      metals (especially copper); second, they show that TCTP can also be under
      transcriptional control, therefore upregulation is not limited to translational
      modifications as TCTP's nomenclature suggests.

PMID- 9655923
TI  - HIV-1 Gag binds specifically to RNA stem-loops in the 5' leader sequence.
AB  - GST-Gag(p55) binds specifically to HIV-1 RNA sequences 1-406, in vitro, with a Kd
      of about 50 nM. This RNA transcript contains a number of stem loop (SL)
      structures. The binding is due to the Gag moiety of the fusion protein, not GST.
      There is a high affinity binding site for Gag in an RNA containing nucleotides
      325-362. SL4 is predicted by both biochemical studies and computer folding to be
      located between nucleotides 335 and 358. An RNA transcript ending at nucleotide
      335 does not bind Gag. The deletion of nucleotides 334-358 from HIV-1 RNAs does
      not affect Gag binding. Digestions with RNase V1 and T1 show that nucleotides 297
      300 in SL2, 310, 312, 313, 315, 317, 318, 325 in SL3, and 342 and 343 in SL4 are
      protected in the presence of Gag. The cleavage of nucleotides 348-351 in SL4 by
      RNAse V1 is enhanced by Gag binding. At least two Gag binding sites are therefore
      located in the leader RNA. Those located 5' of nucleotide 335 require the
      presence of additional 3' sequences.

PMID- 9655924
TI  - Application of alpha-keto acid decarboxylases in biotransformations.
AB  - The advantages of using enzymes in the synthesis of organic compounds relate to
      their versatility, high reaction rates, and regio- and stereospecificity and the
      relatively mild reaction conditions involved. Stereospecificity is especially
      important in the synthesis of bioactive molecules, as only one of the
      enantiomeric forms usually manifests bioactivity, whereas the other is often
      toxic. Although enzymes which catalyze asymmetric carbon-carbon bond formation
      are of great importance in bioorganic chemistry, only a few examples are known
      for thiamin diphosphate (ThDP)-dependent enzymes, whereas transformations using
      e.g. aldolases, lipases and lyases are well documented already. The present
      review surveys recent work on the application of pyruvate decarboxylase and
      benzoylformate decarboxylase in organic synthesis. These enzymes catalyze the
      synthesis of chiral alpha-hydroxy ketones which are versatile building blocks for
      organic and pharmaceutical chemistry. Besides the substrate spectra of both
      enzymes amino acid residues relevant for substrate specificity and
      enantioselectivity of pyruvate decarboxylase have been investigated by site
      directed mutagenesis.

PMID- 9655925
TI  - Minimum CAG repeat in the human calmodulin-1 gene 5' untranslated region is
      required for full expression.
AB  - The human calmodulin-1 gene (hCALM1) contains a (CAG)7 repeat in its 5'
      untranslated region (5'-UTR). We found this repeat to be stable and
      nonpolymorphic in the human population. To determine whether the repeat region
      affects hCALM1 expression and whether repeat expansions to numbers known to be
      associated with disease in other genes may alter expression, we tested luciferase
      reporter genes driven by the hCALM1 promoter and 5'-UTR containing 0, 7 (wild
      type), 20, and 45 CAG repeats in human NT2/D1 teratoma cells. Interestingly, the
      repeat deletion, (CAG)0, decreased expression by 45%, while repeat expansions to
      (CAG)20 and (CAG)45, or the insertion of a scrambled (C,A,G)7 sequence did not
      alter gene expression. These data indicate (1) that the endogenous repeat element
      is required for full expression of hCALM1, and (2) that some triplet repeat
      expansions in the 5'-UTR of protein-coding genes may be well tolerated and even
      optimize gene expression.

PMID- 9655926
TI  - Kzf1 - a novel KRAB zinc finger protein encoding gene expressed during rat
      spermatogenesis.
AB  - Two novel KRAB (Kruppel associated box) type zinc finger protein encoding cDNAs,
      named Kzf1 and Kzf2 (Kzf for KRAB zinc finger), were identified by screening of a
      rat embryonic brain cDNA library with a human ZNF91 KRAB probe. Kzf1 and Kzf2
      encode proteins with an amino-terminal KRAB domain and a carboxy-terminal zinc
      finger cluster containing 9 and 13 zinc finger units, respectively. While Kzf2
      appears to be ubiquitously expressed, Kzf1 is preferentially expressed in the
      testis. Within the testis, Kzf1 mRNA is restricted to germ cells. The Kzf1
      protein exhibits DNA binding activity and its KRAB domain can function as a
      repressor module in transcription. Using somatic cell hybrid analysis, the Kzf1
      gene was mapped to chromosome 6.

PMID- 9655927
TI  - Structure and properties of pyruvate decarboxylase and site-directed mutagenesis
      of the Zymomonas mobilis enzyme.
AB  - Pyruvate decarboxylase (EC 4.1.1.1) is a thiamin diphosphate-dependent enzyme
      that catalyzes the penultimate step in alcohol fermentation. The enzyme is widely
      distributed in plants and fungi but is rare in prokaryotes and absent in animals.
      Here we review its structure and properties with particular emphasis on how site
      directed mutagenesis of the enzyme from Zymomonas mobilis has assisted us to
      understand the function of critical residues.

PMID- 9655928
TI  - Cloning and sequencing of a novel Na+/H+ antiporter gene from Pseudomonas
      aeruginosa.
AB  - We cloned a gene for Na+/H+ antiporter from chromosomal DNA of Pseudomonas
      aeruginosa. Introduction of the gene into host Escherichia coli mutant cells
      lacking all of the major Na+/H+ antiporters enabled the cells to grow in the
      presence of 0.2 M NaCl, although the original host cells could not. Membrane
      vesicles prepared from cells of the transformant possessing the cloned gene
      showed Na+/H+ antiport activity. As a result of DNA sequencing, we found one open
      reading frame (nhaP). The deduced amino acid sequence suggests that the Na+/H+
      antiporter (NhaP) of P. aeruginosa consists of 424 amino acid residues with
      molecular mass of 45486 Da, and hydropathy analysis suggested the presence of 12
      putative transmembrane domains. We found no bacterial Na+/H+ antiporter which
      showed significant sequence similarity with the NhaP in the protein sequence
      database. The NhaP showed partial sequence similarity with animal Na+/H+
      exchangers. Thus, the NhaP of P. aeruginosa is unique among bacterial
      antiporters.

PMID- 9655929
TI  - Up-regulated expression of murine Mcl1/EAT, a bcl-2 related gene, in the early
      stage of differentiation of murine embryonal carcinoma cells and embryonic stem
      cells.
AB  - We have cloned a murine homologue of the human Mcl1/EAT gene, a Bcl-2 related
      gene. Sequence analysis revealed that murine Mcl1/EAT (mMcl1/EAT) has three Bcl-2
      homology domains, two PEST sequences, and immediate response boxes (IRB). The
      presence of IRB indicates that mMcl1/EAT is an immediate-early gene. mMcl1/EAT
      increases dramatically with exposure to retinoic acid in murine embryonal
      carcinoma cell lines (F9 and PCC3) as well as embryonic stem cells, both of which
      are models of early embryogenesis.

PMID- 9655930
TI  - The pyruvate dehydrogenase complex from thermophilic organisms: thermal stability
      and re-association from the enzyme components.
AB  - Examples of pyruvate dehydrogenase complexes, and of its probable precursors, the
      pyruvate ferredoxin oxidoreductases, both isolated from thermophilic organisms,
      are described. The pyruvate ferredoxin oxidoreductases are mostly characterized
      from thermophilic archaea like Sulfolobus solfataricus and Pyrococcus furiosus.
      They retain their catalytic activity up to 60 and 90 degreesC, respectively.
      Characteristic for the thermophilic nature is a biphasic temperature behavior,
      reflecting a more stable low temperature and a metastable high temperature form.
      Another feature is the strong binding of the cofactor thiamin diphosphate.
      Detailed analysis of thermostable pyruvate dehydrogenase complexes so far only
      exist for the enzymes from Bacillus stearothermophilus and Thermus flavus. In
      most respects, especially in the structural features, the enzyme complex from B.
      stearothermophilus resembles its mesophilic counterparts and only an elevated
      temperature maximum for the catalytic activity reveals the thermophilic nature.
      In contrast to this, the more thermostable enzyme complex from T. flavus shows a
      quite distinct behavior. One single protein chain (Mr=100 kDa) instead of an
      alpha2beta2 aggregate was found for the pyruvate dehydrogenase (E1) subunits of
      this enzyme complex. Its catalytic activity is controlled by allosteric
      regulation, while the enzyme complex from B. stearothermophilus shows no such
      regulation. Reversible phosphorylation as a regulatory principle of pyruvate
      dehydrogenase complexes from higher organisms does not take place in the
      thermophilic enzyme complexes. The overall activity of the enzyme complex from B.
      stearothermophilus remains stable at 60 degreesC for 50 min while that from T.
      flavus is active up to 83 degreesC. Thermophilic pyruvate dehydrogenase complexes
      do not spontaneously renature from their separated enzyme components. However,
      chaperonins from Thermus thermophilus stimulate the reactivation of the enzyme
      complex from T. flavus.

PMID- 9655931
TI  - Specific expression of an expansin gene during elongation of cotton fibres.
AB  - A differential screening experiment resulted in the isolation of a full-length
      cDNA clone encoding an expansin from cotton fibres. Nucleotide and derived amino
      acid sequence data showed that pGhEX1 encodes an expansin of 258 amino acids,
      with an N-terminal signal peptide. Northern blot analysis showed that the
      corresponding transcript is abundant in cotton fibre cells but absent in all
      other tissues tested, and that the gene is developmentally regulated during fibre
      elongation.

PMID- 9655932
TI  - Isolation and characterization of cDNA encoding rat heart type acetyl-CoA
      carboxylase.
AB  - We isolated and characterized cDNA clones encoding the entire open reading frame
      (ORF) of a protein consisting of 2456 amino acids with a molecular mass of 276069
      Da from rat heart. As the deduced amino acid sequence showed 85% homology with
      that of human type 2 acetyl-CoA carboxylase (ACC2), we concluded that the cDNA
      clones encode rat heart type ACC2. Using the identified cDNA fragments and the
      reported cDNA fragment of rat type 1 ACC (ACC1), we determined the steady state
      transcript levels of ACC1 and ACC2 in various rat tissues quantitatively by
      Northern blot analysis. The transcript level of ACC2 was high in heart, skeletal
      muscle and brown adipose tissue, which require high energy and mainly metabolize
      fatty acids, whereas that of ACC1 was high in white adipose tissue, which stores
      fatty acids.

PMID- 9655933
TI  - The pyruvate dehydrogenase multi-enzyme complex from Gram-negative bacteria.
AB  - Pyruvate dehydrogenase multi-enzyme complexes from Gram-negative bacteria
      consists of three enzymes, pyruvate dehydrogenase/decarboxylase (E1p),
      dihydrolipoyl acetyltransferase (E2p) and dihydrolipoyl dehydrogenase (E3). The
      acetyltransferase harbors all properties required for multi-enzyme catalysis: it
      forms a large core of 24 subunits, it contains multiple binding sites for the E1p
      and E3 components, the acetyltransferase catalytic site and mobile substrate
      carrying lipoyl domains that visit the active sites. Today, the Azotobacter
      vinelandii complex is the best understood oxo acid dehydrogenase complex with
      respect to structural details. A description of multi-enzyme catalysis starts
      with the structural and catalytic properties of the individual components of the
      complex. Integration of the individual properties is obtained by a description of
      how the many copies of the individual enzymes are arranged in the complex and how
      the lipoyl domains couple the activities of the respective active sites by way of
      flexible linkers. These latter aspects are the most difficult to study and future
      research need to be aimed at these properties.

PMID- 9655934
TI  - Sequence analysis and expression of a novel mouse homolog of Escherichia coli
      recA gene.
AB  - Escherichia coli recA and its yeast homologs RAD51 and DMC1 play crucial roles in
      mitotic and/or meiotic recombination and in repair of double-strand DNA breaks.
      We have identified a murine novel recA-like gene (MmTRAD). The predicted 329
      amino acid protein showed significant homology to mouse Rec2, Rad51, Dmc1 (or
      Lim15) and E. coli RecA. Northern blot analysis revealed that MmTRAD was
      ubiquitously transcribed in various tissues.

PMID- 9655935
TI  - Molecular cloning of a gene encoding phospholipase D from the pathogenic and
      dimorphic fungus, Candida albicans.
AB  - A phospholipase D gene (CaPLD) has been cloned from the Candida albicans genomic
      DNA library. The CaPLD is a member of a highly conserved gene family of PLD and
      has the highest homology to Saccharomyces cerevisiae PLD (SPO14) with an overall
      homology of 42%. Phylogenetic analysis indicated that fungus PLDs including CaPLD
      composed one of the three clusters of PLD genes.

PMID- 9655936
TI  - The human noradrenaline transporter gene contains multiple polyadenylation sites
      and two alternatively spliced C-terminal exons.
AB  - Sequencing downstream of the C-terminal exon 14 of the human noradrenaline
      transporter (hNAT) gene reveals 5 consensus polyadenylation signals, several
      adenylate/uridylate-rich elements (AREs) and a new C-terminal exon, designated as
      exon 15. The tandemly arranged polyadenylation sites are in good conformity with
      the 3.6- and 5.8-kb hNAT mRNA transcripts. Expression of the alternatively
      spliced C-terminal exon 15 is shown by RT-PCR. This alternative splicing event
      proposes additional hNAT mRNA species of 2.4-3 kb in size. Corresponding NAT
      transcripts are found by Northern analysis of human SKN and rat PC12 cell RNA.
      Sequence comparison of the hNAT gene to two bovine NAT cDNAs shows the
      interspecies conservation of this alternative splicing event, the close
      relationship of human and bovine NAT genes, and implicates a functional role for
      the transporters C-terminal domain.

PMID- 9655937
TI  - Gene and subunit organization of bacterial pyruvate dehydrogenase complexes.
AB  - Pyruvate dehydrogenase complexes of bacterial origin are compared with respect to
      subunit composition, organization of the corresponding genes, and the number and
      location of lipoyl domains. Special attention is given to two unusual examples of
      pyruvate dehydrogenase complexes, formed by Zymomonas mobilis and Thiobacillus
      ferrooxidans.

PMID- 9655938
TI  - Molecular cloning and characterisation of a mouse gene encoding an isoform of the
      neuronal cyclin-dependent kinase 5 (CDK5) activator.
AB  - We have isolated and characterised the mouse gene for the p39 activator,
      designated p39is, which encodes a protein of 369 amino acids. The mouse p39
      protein exhibits 95% amino acid identity to a previously characterised human p39
      cDNA and the novel gene sequence corresponds to a single genomic locus in mouse.
      The p39is mRNA is highly expressed in the mouse central nervous system.

PMID- 9655939
TI  - Cloning, structure, chromosomal localization and promoter analysis of human 2
      oxoglutarate dehydrogenase gene.
AB  - Human 2-oxoglutarate dehydrogenase (OGDH) is an E1-component of the OGDH multi
      enzyme complex and catalyzes both the ThDP-dependent decarboxylation of 2
      oxoglutarate and the subsequent reductive succinylation of the lipoyl moiety
      which is covalently bound to the E2 component, dihydrolipoamide
      succinyltransferase. The cDNA and genomic DNA encoding human OGDH has been cloned
      and sequenced. The cDNA contains a 3006-bp open reading frame encoding a 40-amino
      acid leader peptide and a 962-amino acid mature OGDH protein (Mr=108878). The
      gene contains 22 exons spanning approximately 85 kb. The putative ThDP-binding
      sequence motif is identified in both DNAs. The gene is localized to chromosome 7
      at p13-p14 by fluorescence in situ hybridization. With the TATA- and CAAT-less 5'
      flanking region (wild type, -3276/+212) of the OGDH gene-luciferase reporter
      vector construct and its nested deletion or linker-scanning mutant constructs the
      transient reporter expression assays in BHK-21 cells reveal the existence of two
      10-bp cis-acting elements (-53/-44 and -33/-24) and two trans-acting elements (
      536/-496 and -93/-84). A nuclear factor that binds to the region from -63 to -24
      including two cis-acting elements.

PMID- 9655940
TI  - cDNA cloning of mouse BLM gene, the homologue to human Bloom's syndrome gene,
      which is highly expressed in the testis at the mRNA level.
AB  - We cloned a cDNA encoding the mouse homologue to human Bloom's syndrome gene
      (BLM). The deduced amino acid sequence of mouse Blm showed 76% identity to the
      human sequence with very high homology in seven consecutive domains
      characteristic of DNA and RNA helicases. The expression of mBLM mRNA was examined
      in various tissues. Extremely high expression was observed in the testis as
      compared with other tissues. The mBLM mRNA level in the testis began to increase
      12-14 days after birth, corresponding to the appearance of cells in the pachytene
      phase.

PMID- 9655941
TI  - Alternative splicing and structure of the human erythroid dematin gene.
AB  - Human erythroid dematin is a cytoskeletal protein capable of bundling actin
      filaments in vitro. The carboxyl terminal domain of dematin is homologous to the
      headpiece domain of villin, an actin-binding protein of the brush border
      cytoskeleton. Here we report the complete structure of the dematin gene located
      on human chromosome 8p21.1, a region frequently deleted in prostate cancer. The
      dematin gene is composed of 15 exons spanning approximately 15 kb. We also report
      two novel isoforms of dematin derived from alternative splicing of the dematin
      gene in the brain.

PMID- 9655942
TI  - Cloning, structural organization and tissue-specific expression of the rabbit
      transferrin gene.
AB  - We cloned the rabbit transferrin (rTf) cDNA and gene, and quantified the
      expression of the rTf gene at the RNA level in various organs. The tissue
      specific pattern of expression of rTf gene is different to those in other
      species, with a high expression in mammary gland and kidney. The exon/intron
      structure of the rTf gene (17 exons/16 introns) is similar to those of
      transferrins from other species. The sequence of the rTf cDNA already published
      is corrected and lengthened in the 5' region, and a likely polymorphism is
      documented.

PMID- 9655943
TI  - Crystallography and mutagenesis of transketolase: mechanistic implications for
      enzymatic thiamin catalysis.
AB  - The ThDP dependent enzyme transketolase is a convenient model system to study
      enzymatic thiamin catalysis. Crystallographic studies of the enzyme have
      identified the ThDP binding fold, the V-conformation of ThDP as the relevant
      conformation in enzymatic catalysis and details of enzyme-substrate interactions.
      Based on this structural information, the function of various active site
      residues in substrate binding and catalysis has been probed by site-directed
      mutagenesis.

PMID- 9655944
TI  - Cloning and analysis of a transcript derived from two contiguous genes of the
      cathelicidin family.
AB  - Bac4 is a bovine cathelicidin gene contiguous to another member of this family
      named Bac7. Although mutations in the sequence suggested that Bac4 gene might be
      non-functional, primers based on Bac4 specific sequences allowed amplification of
      a 900 bp cDNA. The transcript comprises the sequences of exons 1, 2 and 3 of
      Bac7, and of exons 2, 3 and 4 of Bac4 gene and may result from a weak termination
      control of the transcription of the upstream Bac7 gene.

PMID- 9655945
TI  - Biochemical and genetic characterization of three molybdenum cofactor
      hydroxylases in Arabidopsis thaliana.
AB  - Aldehyde oxidases and xanthine dehydrogenases/oxidases belong to the molybdenum
      cofactor dependent hydroxylase class of enzymes. Zymograms show that Arabidopsis
      thaliana has at least three different aldehyde oxidases and one xanthine oxidase.
      Three different cDNA clones encoding putative aldehyde oxidases (AtAO1, 2, 3)
      were isolated. An aldehyde oxidase is the last step in abscisic acid (ABA)
      biosynthesis. AtAO1 is mainly expressed in seeds and roots which might reflect
      that it is involved in ABA biosynthesis.

PMID- 9655947
TI  - [Protein phosphatase as a partner of protein kinase].

PMID- 9655946
TI  - Biosynthesis of 2-aceto-2-hydroxy acids: acetolactate synthases and
      acetohydroxyacid synthases.
AB  - Two groups of enzymes are classified as acetolactate synthase (EC 4. 1.3.18).
      This review deals chiefly with the FAD-dependent, biosynthetic enzymes which
      readily catalyze the formation of acetohydroxybutyrate from pyruvate and 2
      oxobutyrate, as well as of acetolactate from two molecules of pyruvate (the
      ALS/AHAS group). These enzymes are generally susceptible to inhibition by one or
      more of the branched-chain amino acids which are ultimate products of the
      acetohydroxyacids, as well as by several classes of herbicides (sulfonylureas,
      imidazolinones and others). Some ALS/AHASs also catalyze the (non-physiological)
      oxidative decarboxylation of pyruvate, leading to peracetic acid; the possible
      relationship of this process to oxygen toxicity is considered. The bacterial
      ALS/AHAS which have been well characterized consist of catalytic subunits (around
      60 kDa) and smaller regulatory subunits in an alpha2beta2 structure. In the case
      of Escherichia coli isozyme III, assembly and dissociation of the holoenzyme has
      been studied. The quaternary structure of the eukaryotic enzymes is less clear
      and in plants and yeast only catalytic polypeptides (homologous to those of
      bacteria) have been clearly identified. The presence of regulatory polypeptides
      in these organisms cannot be ruled out, however, and genes which encode putative
      ALS/AHAS regulatory subunits have been identified in some cases. A consensus
      sequence can be constructed from the 21 sequences which have been shown
      experimentally to represent ALS/AHAS catalytic polypeptides. Many other sequences
      fit this consensus, but some genes identified as putative 'acetolactate synthase
      genes' are almost certainly not ALS/AHAS. The solution of the crystal structures
      of several thiamin diphosphate (ThDP)-dependent enzymes which are homologous to
      ALS/AHAS, together with the availability of many amino acid sequences for the
      latter enzymes, has made it possible for two laboratories to propose similar,
      reasonable models for a dimer of catalytic subunits of an ALS/AHAS. A number of
      characteristics of these enzymes can now be better understood on the basis of
      such models: the nature of the herbicide binding site, the structural role of FAD
      and the binding of ThDP-Mg2+. The models are also guides for experimental testing
      of ideas concerning structure-function relationships in these enzymes, e.g. the
      nature of the substrate recognition site. Among the important remaining questions
      is how the enzyme suppresses alternative reactions of the intrinsically reactive
      hydroxyethylThDP enamine formed by the decarboxylation of the first substrate
      molecule and specifically promotes its condensation with 2-oxobutyrate or
      pyruvate.

PMID- 9655948
TI  - [Protein serine/threonine phosphatases].

PMID- 9655949
TI  - [Structural biology of PP1].

PMID- 9655950
TI  - [The structure and regulatory mechanisms of protein phosphatase 2A].

PMID- 9655951
TI  - [The structure and regulation of calcineurin].

PMID- 9655952
TI  - [Structure and function of mammalian protein phosphatase 2C].

PMID- 9655953
TI  - [Neoplastic alterations of protein phosphatases and their significance].

PMID- 9655954
TI  - [Role of myosin phosphatase in smooth muscle contraction].

PMID- 9655955
TI  - [Control of M-phase progression by protein phosphatases].

PMID- 9655956
TI  - [Regulation of functions of intermediate filaments by protein phosphatases].

PMID- 9655957
TI  - [Dephosphorylation of cytoskeletal proteins: phosphorylation and
      dephosphorylation of microtubule proteins].

PMID- 9655958
TI  - [Protein phosphatase 2A in the control of cell function].

PMID- 9655959
TI  - [Calcineurin-mediated signal transduction pathways in yeast].

PMID- 9655960
TI  - [Possible involvement of protein Ser/Thr phosphatase in leukemic cell
      differentiation and proliferation].

PMID- 9655961
TI  - [Physiological role of calcineurin in central nervous system].

PMID- 9655962
TI  - [The role of calcineurin in the regulation of transcription factors].

PMID- 9655963
TI  - [Negative regulation of the stress-activated protein kinase pathway by protein
      phosphatases].

PMID- 9655964
TI  - [Neuronal plasticity and protein phosphatase].

PMID- 9655965
TI  - [Regulatory proteins of type 1 protein phosphatase].

PMID- 9655966
TI  - [Total synthesis and conformational analysis of inhibitors].

PMID- 9655967
TI  - [Naturally occurring toxins with specific inhibitory activity against protein
      serine/threonine phosphatases 1 and 2A].

PMID- 9655968
TI  - [Tumor promotion by inhibitors of protein phosphatase 1 and 2A].

PMID- 9655969
TI  - [Genomic instability induced by a protein phosphatase inhibitor okadaic acid].

PMID- 9655970
TI  - [Multiple actions of tacrolimus and cyclosporin A as specific inhibitors of
      calcineurin].

PMID- 9655971
TI  - [Structure and function of protein tyrosine phosphatases].

PMID- 9655972
TI  - [Role of tyrosine phosphatases in neuronal differentiation].

PMID- 9655973
TI  - [The roles of protein tyrosine phosphatases during hematopoietic progenitor cell
      development and differentiation].

PMID- 9655974
TI  - [Involvement of PTP-U2 in terminal differentiation and apoptosis of leukemia
      cells].

PMID- 9655975
TI  - [Structure, expression and functions of receptor-type protein tyrosine
      phosphatase RPTP-BK in central nervous system].

PMID- 9655976
TI  - [Regulation of lymphocyte signal transduction by protein tyrosine phosphatases].

PMID- 9655977
TI  - [Protein tyrosine phosphatases in the signal transduction pathways of cell
      adhesion].

PMID- 9655978
TI  - [Involvement of protein tyrosine phosphatases in cancer development].

PMID- 9655979
TI  - [FAP-1: a protein tyrosine phosphatase that is involved in Fas-mediated
      apoptosis].

PMID- 9655980
TI  - [Roles of protein-tyrosine phosphatases in insulin-mediated signal transduction
      system].

PMID- 9655981
TI  - [Protein phosphatase studies that I experienced].

PMID- 9655982
TI  - [Basic concepts in insurance medicine. Life insurance. Positive and negative
      performance picture].

PMID- 9655983
TI  - [State control of human existence: being free instead of freedom].

PMID- 9655984
TI  - [Possibilities and risks of genetic diagnosis].
AB  - In the recent past, cytogenetic and molecular genetic methods led to an enormous
      increase in knowledge on genetic information. It reveals a correlation between
      the genetic information and the phenotype of an individual. Therefore, new
      starting points concerning the origin of diseases arise. A new nosology will
      develop. It will force researchers to emphasize more and more on the contribution
      of the--disturbed--genetic information system to the development of diseases.
      They will routinely carry out genome analyses on the following four already
      established levels: 1. phenotype level, 2. biochemical level, 3. chromosomal
      level, 4. molecular genetic level. Practicians mustn't close their mind to these
      new possibilities and methods: The three classical tasks of medicine--diagnosis,
      prevention and therapy--will be supplemented considerably by an earlier
      (presymptomatic) and more precise diagnosis that is furthermore independent of
      the organ. Moreover, there is the increasing possibility to predict the risk to
      develop a disease for descendants in certain partnerships more precisely and, if
      necessary, to diagnose prenatally. From the medical point of view, these advances
      are predominantly positive and to the patient's benefit. But it is pointed out
      that the diagnostic progress also raises new problems which were previously
      unknown. The answers will have to be given by society as a whole.

PMID- 9655985
TI  - [AIDS and life insurance in Germany. 10 years successful risk management].
AB  - The introduction of AIDS specific measures by the German life assurance industry
      in 1988 was an important step towards prevention of adverse selection by the well
      known risk groups. In retrospect one can state that in the eighties there was a
      tendency of risk groups for inappropriately high insurance coverage. This could
      be curtailed with the introduction of a question as to a positive HIV test in
      each proposal form and a mandatory HIV test for every policy exceeding DM
      250,000. These tendencies could very nicely be demonstrated by studies of own
      AIDS cases. The claims for death and disability benefits because of AIDS are as
      of now compared to the total claims of minor importance.

PMID- 9655986
TI  - [MCS, CFS, FMS, SBS and other "modern" illnesses].
AB  - Common "environmental illnesses" are outlined with respect to their history and
      case definition. As no objective diagnostic criteria are available, these
      diagnoses may only be applied after sufficient exclusion of other known diseases.
      Profound knowledge regarding the etiology of these conditions is still lacking,
      and scientifically based somatic concepts for their therapy do not exist. Thus
      there is room for a multitude of unvalidated methods for diagnosis and therapy,
      and alleged causes are readily offered. The psychologic and economic consequences
      for the affected individuals are sometimes deleterious, the costs are a growing
      public concern. Proposals are made for the management of cases of suspected
      environmental illness.

PMID- 9655987
TI  - [Psychosomatic aspects of sudden deafness].
AB  - In a psychosomatic point of view in an overwhelming number of cases sudden
      deafness is a "response" to strain, which consciously or unconsciously is not
      assessed as tolerable. Special personal or situational circumstances seem to
      occur frequently, besides of psychomental strain above all high pressure of
      responsibility in situations of care, high sensibility and inhibition to show
      overt aggressive behaviour, which is suppressed by guilt feelings. These findings
      are used to develop a first idealtypic psychopathogenetic model of sudden
      deafness. Detecting and talking about the individual psychosocial strain of the
      patient is very important in the management of the disease and the social
      medicine assessments, especially in determining duration of disablement and
      estimating grade of disability (GdB) in the case of persistent decrease of
      hearing and tinnitus.

PMID- 9655988
TI  - [Erroneous arguments on remaining risk in medical malpractice].

PMID- 9655989
TI  - A gentamicin order form improves its use.
AB  - To assess the effects of implementing a standardized order form on the
      prescribing and monitoring of gentamicin sulfate at a nonteaching Veterans
      Affairs Medical Center, we prospectively evaluated the prescribing and monitoring
      of gentamicin for 14 months after the use of such a form was implemented. The
      data collected included dosing, initial serum gentamicin concentrations, and
      serum creatinine measurements. These data were compared with similar data
      obtained during a period of 6 months before the order form was used. A total of
      76 patient records were reviewed, 39 before the use of the order form and 47
      after the order form was implemented. Gentamicin peak concentrations were
      statistically higher in the group treated after the order form was implemented.
      No differences were seen in gentamicin trough concentrations. The timely
      measurement of serum gentamicin concentrations and serum creatinine levels was
      improved in the group for whom the order form was used. The order form was
      completed satisfactorily in 44 patients (94%). We conclude that implementing a
      standardized order form improved the use of gentamicin.

PMID- 9655990
TI  - Preventive health services and access to care for male veterans compared with
      their spouses.
AB  - The Veterans Health Administration is exploring ways to reform the current
      Veterans Affairs (VA) system in accordance with the changing health care
      environment of managed care. One proposal is for the VA to enlarge its patient
      base by expanding eligibility to include spouses of veterans. To compare reported
      preventive health care services received by male veterans and their spouses and
      to measure whether spouses would choose to receive their medical care through a
      VA medical center, we randomly selected 230 married male veterans and mailed self
      administered questionnaires to be completed by them and their spouses; 170 (74%)
      eligible subjects completed the questionnaire. The mean age of the veterans and
      spouses was 73.6 and 67.4 years, respectively. Veterans reported significantly
      higher rates of receipt of recommended preventive services than their spouses in
      all 5 areas assessed, including blood pressure measurement; influenza,
      pneumococcal, and tetanus vaccinations; and serum cholesterol measurement.
      Veterans were significantly more satisfied than their spouses with their current
      health care. Finally, 83% (95% confidence interval, 77% to 89%) of spouses
      reported that they would choose to receive their medical care at the VA medical
      center is allowed to do so. These findings suggest that spouses of male veterans
      represent a sizable group that could be incorporated in the VA system, especially
      given their strong desire to do so.

PMID- 9655991
TI  - Quality of diabetes care for non-English-speaking patients. A comparative study.
AB  - To determine the quality of care provided to non-English-speaking patients with
      non-insulin-dependent (type 2) diabetes mellitus compared with English-speaking
      patients, we did a retrospective cohort study of 622 patients with type 2
      diabetes, of whom 93 were non-English-speaking and 529 were English-speaking.
      They were patients at primary and specialty care clinics at a university and a
      county hospital, and the study was based on clinical and administrative database
      records with a 12-month follow-up. Professional interpreters were provided to all
      non-English-speaking patients. Patients were identified using interpreter
      services records, which reliably included all patients who did not speak English.
      After adjusting for demographic differences, significantly more non-English
      speaking patients received care that met the American Diabetes Association
      guidelines of 2 or more glycohemoglobin tests per year (odds ratio, 1.9; 95%
      confidence interval, 1.2-3.0) and 2 or more clinic visits per year (odds ratio,
      2.6; 95% confidence interval, 1.2-5.4). More non-English-speaking patients had 1
      or more dietary consultations (odds ratio, 2.8; 95% confidence interval, 1.3
      6.1). No other significant differences were found in routine laboratory test use
      or in the number of ophthalmologic examinations. Outcome variables also did not
      differ, including standardized glycohemoglobin and other laboratory results,
      complication rates, use of health services, and total charges. At these
      institutions, the quality of diabetes care for non-English-speaking patients
      appear to be as good as, if not better than, for English-speaking patients.
      Physicians may be achieving these results through more frequent visits and
      laboratory testing.

PMID- 9655992
TI  - Feces, dead horses, and fleas. Evolution of the hostile use of biological agents.
AB  - Selected events in the history of biological weapons are highlighted to increase
      physicians' awareness of the threat of biological weapons. The hostile use of
      biological substances originated in antiquity and pervades the history of human
      conflict. Although difficult to verify at times, the use of such weaponry has not
      been limited to national militaries. Disgruntled civilians and even physicians
      have used biological weapons to promote their interests. Their potency, cost
      effectiveness, and the ability to manufacture and deploy them with little
      sophistication, or under the semblance of legitimate commercial endeavors, will
      ensure that biological weapons remain a constant threat to public health.

PMID- 9655993
TI  - Overview of anesthesia for primary care physicians.
AB  - Primary care physicians are frequently asked to evaluate patients before elective
      surgery. Familiarity with anesthetic technique and physiologic processes can help
      primary care physicians identify risk factors for perioperative complications,
      optimize patient care, and enhance communication with surgeons and
      anesthesiologists. To this end, we review the physiologic processes accompanying
      tracheal intubation and general and regional anesthesia. There is no convincing
      evidence that regional anesthesia is safer than general anesthesia. In addition
      to replacing fluid losses from the surgical field and insensible losses,
      intraoperative fluid administration may attenuate the cardiovascular and renal
      effects of anesthesia. Therefore, recommendations to limit fluids should be made
      with caution and should be tempered with an understanding of intraoperative fluid
      requirements. An understanding of the physiologic processes of anesthesia,
      combined with preoperative risk stratification strategies, will enhance a primary
      care physician's ability to provide meaningful preoperative evaluations.

PMID- 9655994
TI  - Mild cobalamin deficiency.

PMID- 9655995
TI  - Cardiac troponins in patients with chest pain.

PMID- 9655996
TI  - Factors V Leiden and the prothrombin gene mutation: two common genetic defects
      associated with thrombosis.

PMID- 9655997
TI  - Prostate carcinoma: clarification through clinical insight and molecular
      diagnostics.

PMID- 9655998
TI  - Finding the iron in the melting pot--practical use of a new genetic assay for
      hereditary hemochromatosis.

PMID- 9655999
TI  - Homocysteine and vascular disease: emerging connections.

PMID- 9656000
TI  - Follow-up testing after cancer treatment: is it indicated?

PMID- 9656001
TI  - Noninvasive positive pressure mechanical ventilation.

PMID- 9656002
TI  - Treatment of gastroesophageal reflux disease--1998.

PMID- 9656003
TI  - Beta-adrenergic blockers in the management of heart failure.

PMID- 9656004
TI  - Diabetes in older persons: special considerations.

PMID- 9656005
TI  - Measles outbreak at a university without a two-dose immunization requirement.

PMID- 9656006
TI  - 'Virtual' factitious disorders and Munchausen by proxy.

PMID- 9656007
TI  - Medical marijuana.
AB  - Although many clinical studies suggest the medical utility of marijuana for some
      conditions, the scientific evidence is weak. Many patients in California are self
      medicating with marijuana, and physicians need data to assess the risks and
      benefits. The only reasonable solution to this problem is to encourage research
      on the medical effects of marijuana. The current regulatory system should be
      modified to remove barriers to clinical research with marijuana. The NIH panel
      has identified several conditions for which there may be therapeutic benefit from
      marijuana use and that merit further research. Marijuana should be held to the
      same evaluation standards of safety and efficacy as other drugs (a major flaw in
      Proposition 215) but should not have to be proved better than current medications
      for its use to be adopted. The therapeutic window for marijuana and THC between
      desired effect and unpleasant side effects is narrow and is a major reason for
      discontinuing use. Although the inhaled route of administration has the benefit
      of allowing patients to self-titrate the dose, the smoking of crude plant
      material is problematic. The NIH panel recommended that a high priority be given
      to the development of a controlled inhaled form of THC. The presence of a
      naturally occurring cannabinoid-receptor system in the brain suggests that
      research on selective analogues of THC may be useful to enhance its therapeutic
      effects and minimize adverse effects.

PMID- 9656008
TI  - Getting the work done.

PMID- 9656009
TI  - Beware of what you say...

PMID- 9656010
TI  - Prevalence and distribution of anorectal misdiagnoses.

PMID- 9656011
TI  - Brucella abortus strain RB51 vaccine: its advantages and risks.

PMID- 9656012
TI  - FSIS assessing risk of Salmonella enteritidis in eggs.

PMID- 9656013
TI  - Beef quality assurance program may need further implementation.

PMID- 9656014
TI  - Debate regarding homeopathic medicine continues.

PMID- 9656015
TI  - Viewpoint on vaccination guidelines and alternative modalities.

PMID- 9656016
TI  - Solution to pet overpopulation may involve change in perspective.

PMID- 9656017
TI  - What is your diagnosis? Fracture of the caudal diaphysis of the left
      ceratobranchial bone of the hyoid apparatus in a goose.

PMID- 9656018
TI  - What is your neurologic diagnosis? Anomalous development of C3 and C4 resulting
      in subluxation and spinal cord compression at C3-4.

PMID- 9656019
TI  - Animal behavior case of the month. Stereotypical motor behavior that manifested
      when the owner departed or was out of the dog's sight.

PMID- 9656020
TI  - Municipal animal control ordinances--some legal issues.

PMID- 9656021
TI  - Prevention of antibiotic residues in veal calves fed colostrum.

PMID- 9656022
TI  - Adverse events associated with albendazole and other products used for treatment
      of giardiasis in dogs.

PMID- 9656023
TI  - Prevalence of fecal shedding of Salmonella organisms among captive green iguanas
      and potential public health implications.
AB  - OBJECTIVE: To determine prevalence of fecal shedding of Salmonella organisms
      among captive green iguanas (Iguana iguana). DESIGN: Cohort study. ANIMALS: 12
      captive green iguanas. PROCEDURE: Iguanas were isolated in an environmental
      chamber, and fecal samples were collected weekly for 10 consecutive weeks.
      Samples were incubated aerobically in tetrathionate broth for 18 to 24 hours.
      Aliquots were then transferred to Hektoen and Salmonella-Shigella agar plates and
      incubated for an additional 18 to 24 hours. Isolated colonies were subcultured on
      nutrient agar slants, and Salmonella isolates were serogrouped and serotyped.
      RESULTS: All 12 iguanas were found to be shedding Salmonella organisms at least
      once during the study, and multiple serotypes were isolated from 7 of the 12.
      Salmonella organisms were isolated from 88 of 106 (83%) fecal samples; 21 samples
      contained multiple Salmonella serotypes. Overall, 11 Salmonella serotypes were
      identified. In 74 of 100 instances, when a particular Salmonella serotype was
      isolated from an individual iguana, the same serotype was also isolated from a
      subsequent fecal sample from that iguana. CLINICAL IMPLICATIONS: Results
      suggested that most iguanas have a stable mixture of Salmonella serotypes in
      their intestinal tracts and intermittently or continuously shed Salmonella
      organisms in their feces. Veterinarians should advise their clients on
      precautions for reducing the risk of acquiring these organisms from their pets.
      Public health officials trying to determine whether an iguana is the source of a
      specific Salmonella serotype that caused infection in human patients should
      submit at least 3 fecal samples collected from the iguana 1 week apart for
      bacterial culture.

PMID- 9656024
TI  - Association of Reptilian and Amphibian Veterinarians guidelines for reducing risk
      of transmission of Salmonella spp from reptiles to humans.

PMID- 9656025
TI  - Use of serologic testing to assess immune status of companion animals.
AB  - At the November 1997 meeting of the AVMA Council on Biologic and Therapeutic
      Agents, the Council recommended that the JAVMA publish an article on the current
      status of the use of serologic testing in an effort to assist practitioners who
      must make decisions regarding vaccination of companion animals (i.e., dogs, cats,
      and horses). It is anticipated that the peer-reviewed article provided here will
      be of benefit to veterinarians and will facilitate their attempts to maintain
      animal health through the knowledgeable use of vaccines.

PMID- 9656026
TI  - Occupational factors and reproductive outcomes among a cohort of female
      veterinarians.
AB  - OBJECTIVE: To estimate absolute and relative risks of preterm delivery (PTD) and
      small-for-gestational-age (SGA) births among a cohort of female veterinarians in
      relation to selected occupational factors, including clinical practice type
      (CPT). DESIGN: Retrospective cohort survey. SAMPLE POPULATION: 2,997 female
      graduates from US veterinary colleges between 1970 and 1980. PROCEDURE: Relevant
      health and occupational data were collected through a self-administered mail
      questionnaire with telephone follow-up of nonrespondents. Absolute and relative
      risks of PTD and SGA births were estimated in relation to maternal CPT at the
      time of conception and exposure to 13 occupational factors. Attempts were made to
      control confounding by use of multiple logistic regression analyses. RESULTS:
      Absolute and relative risks of PTD were highest for veterinarians employed in
      exclusively equine clinical practice. Although several increased, none of the CPT
      specific relative risk estimates were significantly different from the null value
      of 1. Exposure-specific analyses indicated that occupational involvement with
      solvents among exclusively small animal practitioners was associated with the
      highest relative risk of PTD. A small number of SGA births limited information
      that could be obtained from these analyses. Overall absolute risks of PTD and SGA
      births among cohort members were much lower in comparison with the general female
      population. CLINICAL IMPLICATIONS: Given the large number of women currently
      practicing and entering the profession of veterinary medicine, clinical tasks
      associated with potential reproductive hazards should be approached with
      heightened awareness and increased caution, especially activities that may
      involve exposure to solvents.

PMID- 9656027
TI  - Serum distemper virus and parvovirus antibody titers among dogs brought to a
      veterinary hospital for revaccination.
AB  - OBJECTIVE: To determine serum canine distemper virus (CDV) and canine parvovirus
      (CPV) antibody titers in healthy dogs brought to a veterinary hospital for
      revaccination. DESIGN: Case series. ANIMALS: 122 dogs. PROCEDURE: Serum antibody
      titers were measured by means of hemagglutination inhibition (CPV titers) or
      serum neutralization (CDV titers) at the time dogs were brought to the hospital
      for revaccination. All dogs had been vaccinated between 271 and 1,665 days
      previously. Dogs were grouped by age, breed (purebred vs mixed breed), sex, and
      weight to determine whether these factors were associated with antibody titers.
      Serum CPV titers > or = 1:80 and serum CDV titers > or = 1:96 were considered
      protective. RESULTS: Breed, sex, and weight were not significantly associated
      with serum CPV and CDV titers. Age was significantly associated with CPV titer,
      with younger dogs having higher titers, but was not associated with CDV titer.
      Thirty-three of 122 (27%; 95% confidence interval, 19.0 to 34.9%) dogs had a less
      than-protective CPV titer. Twenty-five of 117 (21%; 95% confidence interval, 13.6
      to 28.4%) dogs had a less-than-protective CDV titer. CLINICAL IMPLICATIONS:
      Results suggest that, on the basis of serum antibody titers, the current practice
      of annual revaccination of dogs against CPV and CDV infection should be
      maintained. Measurement of antibody titers to determine whether revaccination is
      truly needed would seem justifiable in those dogs that have previously had an
      adverse reaction to vaccination.

PMID- 9656028
TI  - Use of infrared thermometry and effect of otitis externa on external ear canal
      temperature in dogs.
AB  - OBJECTIVE: To compare infrared thermometry with rectal thermometry as a method of
      assessing core body temperature in dogs and to assess the effect of otitis
      externa on external ear canal temperature (EECT). DESIGN: Prospective study.
      ANIMALS: 650 dogs without history or clinical signs of otitis externa and 85 dogs
      with recurrent or chronic otitis externa. PROCEDURE: Rectal temperature was
      measured, using a mercury thermometer. External ear canal temperature was
      measured, using an infrared tympanic thermometer. RESULTS: Measurements of body
      temperature at the 2 sites did not agree. Sensitivity and specificity of infrared
      thermometry in detecting fever, as determined by rectal thermometry, were 69.7
      and 84.6%, respectively. Use of methods to predict rectal temperature from EECT
      did not improve the accuracy of infrared thermometry. Otitis externa
      significantly influenced EECT. CLINICAL IMPLICATIONS: Use of infrared thermometry
      as a replacement for rectal thermometry in assessing core body temperature in
      dogs was unsatisfactory. The 2 methods for measuring body temperature were not
      interchangeable in dogs.

PMID- 9656029
TI  - Preoperative variables affecting long-term outcome of triple pelvic osteotomy for
      treatment of naturally developing hip dysplasia in dogs.
AB  - OBJECTIVE: To determine whether preoperative radiographic evidence of
      degenerative joint disease (DJD), hip joint laxity, or age at surgery is
      associated with long-standing DJD or hip function in dogs with hip dysplasia (HD)
      that had a triple pelvic osteotomy (TPO). DESIGN: Prospective study. ANIMALS: 34
      dogs with HD. PROCEDURE: Dogs that had TPO performed during an 8-year period were
      chosen for long-term follow-up evaluation that included physical examinations,
      pelvic radiographs, and owner questionnaires. Data on radiographic evidence of
      DJD, Norberg angle, and percentage of femoral head coverage were retrieved from
      preoperative records and determined from follow-up radiographs. RESULTS:
      Approximately 40% of dogs had progression of DJD. Eighty-seven percent of dogs
      received excellent or good physical examination scores, and 76% received
      excellent or good at-home activity scores. Preoperative and long-standing DJD
      were not associated. The risk of DJD was increased with increased age at surgery,
      narrower preoperative Norberg angle, and lower percentage of femoral head
      coverage, but these variables were not associated with clinical hip function.
      CLINICAL IMPLICATIONS: TPO for treatment of HD in dogs may slow, rather than
      stop, radiographic progression of DJD; however, clinical outcome is acceptable
      for most dogs. Preoperative evidence of DJD may not be a limiting criterion in
      selecting dogs as suitable TPO candidates. Dogs with extensive hip joint laxity
      before surgery may be predisposed to developing DJD; thus, the risk-to-benefit
      ratio for TPO versus salvage procedures should be considered. Younger dogs may
      develop less severe DJD after TPO; surgery should be considered at the first sign
      of hip joint laxity and pain.

PMID- 9656030
TI  - Response to long-term enzyme replacement treatment in dogs with exocrine
      pancreatic insufficiency.
AB  - OBJECTIVE: To study response to long-term enzyme replacement treatment in dogs
      with exocrine pancreatic insufficiency (EPI). DESIGN: Cross-sectional study.
      ANIMALS: 76 German Shepherd Dogs or rough-coated Collies with EPI and 145
      clinically normal dogs of the same breeds. PROCEDURE: Questionnaires were sent to
      owners of dogs with EPI and owners of clinically normal dogs. Dogs with EPI had
      been given dietary enzyme supplements for at least 4 months. Relative frequency
      distributions of gastrointestinal tract and dermatologic signs, prevalences of
      typical signs of EPI (e.g., weight loss, ravenous appetite, yellow and pulpy
      feces, high fecal volume), feeding regimens, and dietary intolerances were
      compared between dogs with EPI and clinically normal dogs. RESULTS:
      Gastrointestinal tract signs considered typical for dogs with EPI were almost
      completely controlled with dietary enzyme supplements in half of the dogs with
      EPI, and their general health was similar to that of clinically normal dogs. A
      poor treatment response was found in a fifth of dogs with EPI that had several
      signs that were typical of EPI. Signs most often persisting were high fecal
      volume, yellow and pulpy feces, and flatulence. Dermatologic problems were
      common, especially in German Shepherd Dogs with EPI. Treatment response was
      irrespective of breed. Nonenteric-coated enzyme supplements, powdered enzyme, and
      raw chopped pancreas were equally effective in controlling clinical signs.
      Although dietary sensitivities were common, use of adjunctive dietary treatment
      was minimal. Antibiotics were occasionally administered to half of the dogs with
      EPI. CLINICAL IMPLICATIONS: Results of this study indicate that, with basically
      similar treatment regimens, response to long-term enzyme treatment in dogs with
      EPI varied considerably.

PMID- 9656031
TI  - Pneumothorax secondary to Dirofilaria immitis infection in two cats.
AB  - Dirofilariasis was diagnosed in 2 cats with spontaneous pneumothorax. One cat had
      a 3-week history of a cough, and the other had an 11-month history of vomiting
      and tachypnea. Pneumothorax was managed in cats by thoracocentesis and supportive
      care. Diagnosis of dirofilariasis was made on the basis of heartworm antigen and
      antibody test results and radiographic findings. Clinical signs of heartworm
      infection improved after treatment with corticosteroids. Cats had good extended
      outcomes. Heartworm disease should be one of the differential diagnoses
      considered in cats with spontaneous pneumothorax.

PMID- 9656032
TI  - Correlations between ultrasonographic findings and specific hepatic diseases in
      cats: 72 cases (1985-1997).
AB  - OBJECTIVE: To identify correlations between ultrasonographic findings and
      specific hepatic diseases in cats. DESIGN: Retrospective study. SAMPLE
      POPULATION: Medical records of 72 cats with a histopathologic diagnosis of
      hepatic disease and diagnostic-quality abdominal ultrasonograms between 1985 and
      1997. PROCEDURE: Abdominal ultrasonographic findings in 72 cats with
      histologically confirmed hepatic disease (hepatic lipidosis excluded) were
      reviewed. Rather than attempt to combine individual ultrasonographic findings
      with specific hepatic diseases, 2 classification trees were created as models to
      correlate certain groups of abnormalities with specific hepatic diseases or with
      malignant and benign lesions of the liver. Sensitivity and specificity of
      classification trees were calculated. RESULTS: Use of a classification tree
      resulted in correct classification of malignant versus benign hepatic lesions in
      88.9% of cats that had hepatic disease (sensitivity, 90.7%; specificity, 86.1%).
      Use of a classification tree to distinguish individual types of hepatic diseases
      resulted in mostly accurate classification of hepatic lymphosarcoma (sensitivity,
      70.5%; specificity, 98.2%), cholangitis-cholangiohepatitis syndrome (sensitivity,
      87%; specificity, 90%), and benign lesions of the liver (sensitivity, 84.6%;
      specificity, 86.4%). Criteria that helped most in differentiating among various
      hepatic diseases were abnormalities within other organs (spleen, lymph nodes) and
      appearance of the hepatic portal system. A correlation was not found between
      focal or multifocal appearance of hepatic lesions and specific hepatic diseases.
      CLINICAL IMPLICATIONS: Use of classification trees to distinguish among specific
      hepatic diseases or between malignant and benign hepatic lesions provides
      potentially useful algorithms for ultrasonographic evaluation of cats with
      hepatic disease.

PMID- 9656033
TI  - Cycad palm toxicosis in dogs: 60 cases (1987-1997).
AB  - OBJECTIVE: To report clinical and epidemiologic information, summarize
      characteristic clinical signs and laboratory results, and describe the expected
      course of cycad toxicosis in dogs. DESIGN: Retrospective study. ANIMALS: 60 dogs
      with evidence of cycad ingestion. PROCEDURE: The National Animal Poison Control
      Center's case record database was searched for records of dogs ingesting cycad
      plants from January 1987 to November 1997. Data were retrieved on clinical signs,
      laboratory test results, exposure history, and physical examination findings.
      Cases were assessed as toxicosis, suspected toxicosis, or possible toxicosis.
      RESULTS: Records from 60 dogs were retrieved; 89.7% of the dogs were from the
      southern United States, 38.7% ingested seeds, 95% developed liver and
      gastrointestinal tract problems, and 53.3% had abnormal neurologic signs. High
      serum bilirubin concentration and alkaline phosphatase and alanine
      aminotransferase activities were the most common serum biochemical abnormalities.
      Although clinical signs were observed within 1 day, laboratory values did not
      change for 24 to 48 hours after cycad ingestion. Mortality rate was reportedly
      32.1%. CLINICAL IMPLICATIONS: 68% of dogs responded well to treatment and
      supportive care. Dogs ingesting seeds are likely to develop more serious
      problems. Clinical signs can develop within 1 to 3 days and can last for several
      days. A tentative diagnosis should be made on the basis of history of ingestion,
      clinical signs, and duration of signs. Because of the nature of these toxins,
      cycad ingestion is serious and should be treated aggressively.

PMID- 9656034
TI  - Paraneoplastic pruritus and alopecia in a horse with diffuse lymphoma.
AB  - An 8-year-old castrated male Paint Horse was referred because of generalized
      pruritus, alopecia, and intermittent fever. Results of gross evaluation of the
      skin and microscopic evaluation of skin scrapings were inconclusive. Histologic
      examination of skin biopsy specimens revealed vasculitis. The horse had
      persistent hypercalcemia; therefore, lymphosarcoma was considered a possibility.
      Ultrasonography revealed hypoechoic nodules within the parenchyma of the spleen
      and liver. Results of microscopic evaluation of an aspirate from a splenic nodule
      were suggestive of lymphosarcoma. The condition of the horse deteriorated, and it
      was subsequently euthanatized. Postmortem examination revealed diffuse lymphoma.
      In human beings, generalized pruritus may be an indication of serious internal
      disease, including malignancy. Paraneoplastic pruritus is most common in patients
      with Hodgkin's lymphoma but can also develop in patients with non-Hodgkin's
      lymphoma, leukemia, or a solid neoplasm. Lymphoma should be considered in the
      differential diagnoses when examining horses with generalized pruritus for which
      another cause cannot be identified.

PMID- 9656035
TI  - Clinical appearances, healing patterns, risk factors, and outcomes of horses with
      fungal keratitis: 53 cases (1978-1996)
AB  - OBJECTIVE: To compare initial clinical appearances, healing mechanisms, risk
      factors, and outcomes of horses with fungal keratitis. DESIGN: Retrospective
      analysis. ANIMALS: 52 horses (53 eyes) with fungal keratitis. PROCEDURE: Medical
      records and clinical photographs of eyes were reviewed. Keratomycoses were
      categorized on the basis of clinical appearance at initial examination and
      pattern of healing. RESULTS: Five distinct forms of mycotic keratitis were
      recognized. Of 53 affected eyes, 34 (64%) retained sight and had varying degrees
      of corneal scarring after treatment, 6 (11%) had a cosmetic appearance but were
      blind, and 13 (25%) were enucleated. Bacterial-like ulcers were the most frequent
      type and the most difficult for predicting outcome. Eyes affected by superficial
      fungal keratitis were likely to be chronically infected and to require
      debridement and extended treatment but usually healed with minimal scarring.
      Keratomycosis with a surrounding furrow resulted in a grave prognosis.
      Aspergillus organisms were isolated from 9 of 10 such eyes. Cake-frosting
      material was a positive prognostic sign. Fungal corneal stromal abscesses tended
      to be caused by yeast. CLINICAL IMPLICATIONS: This information will aid
      practitioners in recognizing various forms of fungal keratitis and guide them
      when making therapeutic decisions and prognoses for affected horses.

PMID- 9656037
TI  - The invisible profession.

PMID- 9656036
TI  - Comparison of hypertonic saline-dextran solution and lactated Ringer's solution
      for resuscitating severely dehydrated calves with diarrhea.
AB  - OBJECTIVE: To determine effectiveness of rapid i.v. administration of hypertonic
      saline-dextran (HSD) solution combined with oral administration of isotonic
      electrolyte solution for resuscitating severely dehydrated calves and to compare
      the resuscitative response with that of a conventional treatment of lactated
      Ringer's solution (LRS) i.v. and orally administered isotonic electrolyte
      solution. DESIGN: Prospective study. ANIMALS: 15 male dairy calves 3 to 10 days
      old. PROCEDURE: Baseline data were obtained. Osmotic diarrhea and severe
      dehydration were induced for 48 hours. Calves were then allocated to 3 treatment
      groups. The control group (group C) did not receive fluids, a second group (group
      H) received hypertonic saline (7.2% NaCl) solution with 6% dextran 70 and
      isotonic electrolyte solution, and a third group (group L) received LRS and
      isotonic electrolyte solution. Physical examinations were performed every 8
      hours. RESULTS: Calves developed diarrhea, lethargy, severe dehydration (mean,
      14% of body weight), azotemia, hyperkalemia, and mild acidemia. Group-C calves
      remained lethargic and severely dehydrated during the 24-hour treatment phase.
      Calves treated with HSD and LRS were effectively resuscitated; however, response
      for most variables was more rapid and sustained for the HSD-treated group.
      Cardiac output was greater in LRS- than HSD-treated calves 1, 2, and 8 hours
      after initiation of treatment because of continued i.v. administration of fluids.
      CLINICAL IMPLICATIONS: A combination of HSD and isotonic electrolyte solution was
      a rapid and effective method for resuscitation of severely dehydrated calves. It
      was similar in effectiveness to conventional treatment in which LRS and isotonic
      electrolyte solution were used for resuscitating calves with severe dehydration.

PMID- 9656038
TI  - Roles of acute care nurse practitioners, physician assistants, and resident
      physicians in acute care settings.

PMID- 9656039
TI  - A survey of endotracheal suctioning with instillation of normal saline.
AB  - BACKGROUND: Instillation of normal saline before suctioning is a common nursing
      intervention although little research supports the practice. OBJECTIVES: To
      determine when and how often saline is used during suctioning and to assess the
      knowledge of nurses and respiratory therapists of the advantages and dangers of
      using saline during endotracheal suctioning. METHODS: A survey of nurses and
      respiratory therapists working in adult ICUs was conducted in a large university
      teaching hospital. RESULTS: Of the 187 respondents, 96 (51%) rarely instill
      saline before suctioning, whereas 61 (33%) frequently use saline. Fifty-five
      percent use saline to enhance retrieval of secretions, and 45% use it to
      stimulate a cough. Nurses and respiratory therapists differ in their use and
      understanding of saline instillation. Most nurses (64%) rarely use saline before
      suctioning, whereas most respiratory therapists (71%) frequently use saline.
      Respiratory therapists (57%) were more aware than were nurses (37%) of the
      benefit of using normal saline to stimulate a cough. Nurses indicated more
      adverse effects of instillation of normal saline, specifically oxygen
      desaturation and increased risk of pulmonary infections, than did respiratory
      therapists. CONCLUSION: The results of the survey helped determine target areas
      for educational programs for nurses and respiratory therapists. A protocol is
      being developed for use by all who do suctioning.

PMID- 9656040
TI  - Instillation of normal saline before suctioning in patients with pulmonary
      infections: a prospective randomized controlled trial.
AB  - OBJECTIVE: To determine the effect of instillation of normal saline before
      suctioning on oxygen saturation, heart rate, and blood pressure in patients with
      pulmonary infections. METHODS: A prospective randomized controlled trial was
      conducted in the surgical, medical, and burn/trauma ICUs of an academic medical
      center. Eighteen men and 11 women (mean age = 60 years) receiving mechanical
      ventilation who met the criteria for pulmonary infection were randomly assigned
      to 2 groups. One group had instillation of a 5-mL bolus of normal saline before
      suctioning; the other did not. Suctioning was done as needed during an 8-to 12
      hour period. Oxygen saturation, heart rate, and blood pressure were measured
      noninvasively immediately before and after suctioning, at 1-minute intervals for
      5 minutes after suctioning, and at 10 minutes after suctioning. RESULTS:
      Instillation of normal saline had an adverse effect on oxygen saturation, which
      worsened over time. Differences in saturation between the 2 groups were
      significant at 4, 5, and 10 minutes after suctioning. Differences in heart rate
      and blood pressure were not significant. CONCLUSION: Instillation of normal
      saline before suctioning has an adverse effect on oxygen saturation and should
      not be used routinely in patients receiving mechanical ventilation who have
      pulmonary infection.

PMID- 9656041
TI  - Care activities and outcomes of patients cared for by acute care nurse
      practitioners, physician assistants, and resident physicians: a comparison.
AB  - BACKGROUND: Little information is available on the practice of acute care nurse
      practitioners and physician assistants in acute care settings. OBJECTIVES: To
      compare the care activities performed by acute care nurse practitioners and
      physician assistants and the outcomes of their patients with the care activities
      and patients' outcomes of resident physicians. METHODS: Sixteen acute care nurse
      practitioners and physician assistants and a matched group of resident physicians
      were studied during a 14-month period. Data on the subjects' daily activities and
      on patients' outcomes were collected 4 times. RESULTS: Compared with the acute
      care nurse practitioners and physician assistants, residents cared for patients
      who were older and sicker, cared for more patients, worked more hours, took a
      more active role in patient rounds, and spent more time in lectures and
      conferences. The nurse practitioners and physician assistants were more likely
      than the residents to discuss patients with bedside nurses and to interact with
      patients' families. They also spent more time in research and administrative
      activities. Few of the acute care nurse practitioners and physician assistants
      performed invasive procedures on a regular basis. Outcomes were assessed for 187
      patients treated by the acute care nurse practitioners and physician assistants
      and for 202 patients treated by the resident physicians. Outcomes did not differ
      markedly for patients treated by either group. The acute care nurse practitioners
      and physician assistants were more likely than the residents to include patients'
      social history in the admission notes. CONCLUSIONS: The tasks and activities
      performed by acute care nurse practitioners and physician assistants are similar
      to those performed by resident physicians. However, residents treat patients who
      are sicker and older than those treated by acute care nurse practitioners and
      physician assistants. Patients' outcomes are similar for both groups of subjects.

PMID- 9656042
TI  - Patients' outcomes: intrahospital transportation and monitoring of critically ill
      patients by a specially trained ICU nursing staff.
AB  - BACKGROUND: Intrahospital transportation of critically ill patients can
      contribute to patients' morbidity and mortality. OBJECTIVE: To determine adverse
      outcomes associated with intrahospital transportation of critically ill patients
      by a specially trained nursing transport team. METHODS: Monitoring and
      intervention data were collected for 237 instances of transportation of patients
      between a hospital's ICUs and radiology suites. These results were compared with
      the results of national studies on complication rates associated with
      intrahospital transportation of patients. RESULTS: The patients moved by the
      specially trained transport team has a 15.5% overall complication rate, with
      10.2% minor, 2.5% moderate (compensated for with medications), and 2.8% severe
      complications that did not respond to intervention. No medications of therapies
      were delayed, and only 2 patients (0.8%) had decompensation that required the
      examinations to be aborted. Reported national complication rates for
      intrahospital transportation of patients are as high as 75%; the complications
      include adverse events such as delayed administration of medications, significant
      changes in vital signs, dislodgment of artificial airways and i.v. catheters, and
      cardiopulmonary arrest. CONCLUSION: Use of a specially trained ICU transport team
      can substantially reduce the rate of adverse outcomes generated by the
      transportation of critically ill patients for specialized radiological
      procedures.

PMID- 9656043
TI  - Effect of a back massage and relaxation intervention on sleep in critically ill
      patients.
AB  - BACKGROUND: Critically ill patients are deprived of sleep and its potential
      healing qualities, although many receive medications to promote sleep. No one has
      adequately evaluated holistic nonpharmacological techniques designed to promote
      sleep in critical care practice. OBJECTIVES: To determine the effects of (1) a
      back massage and (2) combined muscle relaxation, mental imagery, and a music
      audiotape on the sleep of older men with a cardiovascular illness who were
      hospitalized in a critical care unit. METHODS: Sixty-nine subjects were randomly
      assigned to a 6-minute back massage (n=24); a teaching session on relaxation and
      a 7.5-minute audiotape at bedtime consisting of muscle relaxation, mental
      imagery, and relaxing background music (n=28); or the usual nursing care
      (controls, n=17). Polysomnography was used to measure 1 night of sleep for each
      patients. Sleep efficiency index was the primary variable of interest. One-way
      analysis of variance was used to test for difference in the index among the 3
      groups. RESULTS: Descriptive statistics showed improved quality of sleep among
      the back-massage group. Initial analysis showed a significant difference among
      the 3 groups in sleep efficiency index. Post hoc testing with the Duncan
      procedure indicated a significant difference between the back-massage group and
      the control group; patients in the back-massage group slept more than 1 hour long
      than patients in the control group. However, the variance was significantly
      different among the 3 groups, and reanalysis of data with only 17 subjects in
      each group revealed no difference among groups (P=.06). CONCLUSIONS: Back massage
      is useful for promoting sleep in critically ill older men.

PMID- 9656044
TI  - Intra-aortic balloon pump: nursing implications for patients with an iliac artery
      approach.
AB  - Long-term use of an intra-aortic balloon pump is often necessary for patients
      with severe left ventricular dysfunction who are awaiting cardiac
      transplantation. Complications caused by prolonged bed rest and immobility can
      occur when the traditional femoral approach is used for insertion of the balloon
      catheter. Insertion of the intra-aortic balloon catheter through the iliac artery
      is an alternative technique that allows patients to sit, stand, and walk while
      receiving counterpulsation. This approach is now being used to prevent the
      complications of immobility in patients awaiting cardiac transplantation. In this
      article, the special considerations, potential complications, and nursing
      interventions unique to the iliac artery approach are delineated.

PMID- 9656045
TI  - Manual versus mechanical compression for femoral artery hemostasis after cardiac
      catheterization.
AB  - BACKGROUND: Most cardiac catheterizations are performed via femoral artery
      access. Reported rates of both peripheral vascular complications and success
      rates for the use of manual and mechanical compression techniques to achieve
      femoral artery hemostasis after cardiac catheterization vary. OBJECTIVE: To
      determine is use of a mechanical clamp is as effective as standard manual
      pressure for femoral artery hemostasis after cardiac catheterization. METHODS:
      Subjects consisted of 720 patients from 2 community hospitals who had elective
      diagnostic cardiac catheterization via the femoral artery. The control group
      (n=343) received manual compression for hemostasis; the study group (n=377)
      received mechanical compression. Standard protocols were used for the 2
      compression techniques. Pressure was applied for a minimum of 10 minutes for 5F
      and 6F sheaths and catheters and for a minimum of 15 minutes for 7F and 8F
      sheaths and catheters. Prospective data were collected and analyzed for each
      patients, including sheath or catheter size, blood pressure, height, weight, age,
      time from administration of local anesthetic to successful cannulation of the
      femoral artery, anticoagulation status, total compression time, physician
      performing the catheterization procedure, nurse or technician who obtained
      hemostasis, and complications. In follow-up, patients were asked site-specific
      and functional status questions 1 to 2 days after the catheterization procedure
      and again 3 days after the catheterization procedure. RESULTS: Data were analyzed
      by using frequency distributions, measures of central tendency, and measures of
      variability. Only 1 difference between the 2 groups was significant: manual
      compression time was 14.93 +/- minutes, whereas mechanical compression time was
      17.13 +/- minutes. CONCLUSION: Mechanical compression is as effective as manual
      compression for femoral artery hemostasis after cardiac catheterization.

PMID- 9656046
TI  - In-hospital first-responder automated external defibrillation: what critical care
      practitioners need to know.
AB  - Despite the development and widespread implementation of Basic Life Support and
      Advanced Cardiac Life Support, the percentage of patients who survive in-hospital
      cardiac arrest has remained stable at approximately 15%. Although survival rates
      may approach 90% in coronary care units, survival rates plummet outside of these
      units. The lower survival rates for cardiac arrest that occur outside of the
      coronary care unit may relate to the time elapsed between the onset of
      ventricular fibrillation and first defibrillation. The advent of automated
      external defibrillators has made it possible to decrease the time elapsed before
      first defibrillation in non-critical care areas of the hospital. First responders
      need only recognize that the patient is unresponsive, apneic, and pulseless
      before attaching and activating the automated external defibrillator. Our
      research shows that, as part of Basic Life Support training, non-critical care
      nurses can learn to use the device and can retain the knowledge and skill over
      time. Establishing an in-hospital automated external defibrillator program
      requires commitment from administration, physicians, and nursing personnel.
      Critical care practitioners should be aware of this technology and the literature
      that supports its safety and effectiveness when used by non-critical care first
      responders. Critical care nurses are in a unique position to effect changes that
      will decrease the time between the onset of cardiac arrest and first
      defibrillation.

PMID- 9656047
TI  - The ECG in cardiac stress testing: a valuable, but unappreciated source of clues.
AB  - The ECG exercise stress test is a very potent aid to the clinical diagnosis of
      CAD. Thorough knowledge of the ECG abnormalities and clinical features related to
      the stress test are required for an accurate diagnosis. The ECG exercise stress
      test is not a substitute for clinical acumen. Proper evaluation of the stress
      test is a clinical art of the skilled clinician. ECG exercise stress testing can
      be done efficiently and effectively by trained emergency department physicians.
      As a result, the diagnosis of CAD can be greatly accelerated.

PMID- 9656048
TI  - Results of cardiac troponin I.

PMID- 9656049
TI  - Integrating technology with compassionate care: withdrawal of ventilation in a
      conscious patient with apnea.

PMID- 9656050
TI  - Malignant hyperthermia.

PMID- 9656051
TI  - All the king's horses and all the king's men. Three forms of curative audience in
      the recovery from psychosis.
AB  - This essay discusses an overlooked ingredient in the psychotherapy of psychosis
      which is termed the "curative audience." Central to the equation of psychological
      selfhood is the evocation of a sense of self by experiences that the patient has
      with objects in the environment. This essay calls attention to an essential
      function of this environment, namely, that it provides an audience that makes it
      possible for these "selfobject" transferences, transference interpretations or
      new, helpful relational experiences to become significant. In essence, it is
      argued that a "private experience" without an internal or external audience is
      not therapeutic in the reassembly of self, especially when the power and
      intensity to overcome psychotic disintegration is required. The idea that the
      psychotic patient recompensates not only with the help of a therapist but under
      the auspices of a third entity, has not been previously discussed. Interestingly,
      all the schools of psychoanalysis have touched on the role of audience in the
      healing of patients with both neurosis and psychosis, yet this thread has not
      been followed into its binding together of subjectivity. Three forms of curative
      audience can be identified corresponding to the beginning, middle, and end phases
      of treatment. The role of audience in the reassembly of the self is taking its
      first form in the initial contact or initial relationship with the other and over
      time develops into the second form, the therapeutic alliance. In the third form
      of the curative audience, the establishment of an external selfobject milieu that
      performs the functions of the curative audience is seen as essential to continued
      cohesion in the recovery from psychosis. Performative statements exert self
      cohering effects and can be seen to have their source in the curative audience.
      Two clinical vignettes were presented to illustrate these ideas.

PMID- 9656052
TI  - The contributions of self psychology to the treatment of anorexia and bulimia.
AB  - This article reviews the contribution of self psychology to the treatment and
      understanding of anorexia and bulimia. It tries to show that the unique
      conceptualization of self, selfobject relations, and this theory's
      conceptualization of resistance and defenses constitutes a therapeutic stance
      which especially fits the therapeutic needs of eating-disordered patients.
      Clinical vignettes illuminate three main issues exemplifying the opportunities
      and dilemmas that this new development in psychoanalytic theory brings to the
      fore in the treatment of eating disorders: (1) empathy with deeds and attitudes
      of the patient that the therapist finds difficult to empathize with; (2) empathic
      understanding "from within" from an experience-near stance vs. experience-distant
      interpretation "from without"; (3) self, selfobject relations with food and as a
      result of progress in therapy, with human beings.

PMID- 9656053
TI  - Responsibilities of the psychotherapy supervisor.
AB  - The art and skill of psychotherapy supervision and its teaching have received
      relatively little attention compared to their importance in psychiatric
      education. Supervision is a complex task, requiring teaching and clinical skills,
      as well as an awareness of the numerous responsibilities of the position. We
      describe the responsibilities of the supervisor and group them to include those
      to the supervise, to the patient, to the training program and profession, and to
      the supervisor himself or herself. The core responsibility to supervise is
      teaching them how to be psychiatrists, which for supervisors requires a balance
      between a hierarchical and collaborative approach. The primary responsibility to
      patients is that of assuring satisfactory treatment. Evaluating supervise within
      an educational framework is the primary responsibility to the training program
      and profession. Finally, the responsibilities to the supervisors themselves
      include self-examination during the supervision process and general ongoing
      education. Several themes are highlighted. One theme, which is a central
      development in the understanding of supervision, is seeing the supervisor as a
      participant in the supervisory process, rather than an outside observer of the
      therapy process. Another theme is that these responsibilities are at times
      competing, requiring the supervisor to establish priorities. Vignettes are used
      throughout to illustrate the problems and subtleties of supervision.

PMID- 9656054
TI  - Cultural intersections in the psychotherapy of borderline personality disorder.
AB  - Psychotherapy can be essentially considered a journey in which two individuals
      embark, each carrying a formidable cultural legacy. The psychotherapeutic
      enterprise then becomes a succession of stops and intersections as the two
      protagonists struggle to identify their culturally determined behaviors, using
      culturally determined procedures to take care of them. In this sense, cultural
      procedures are not a technical term but the appropriate combination of learned
      concepts, experiential modifiers, and common sense indicators of contemporary
      realities both at the individual and collective levels. The fascinating and
      challenging nature of BPD does have a significant cultural component encompassing
      explanatory, interpretive, pathogenic, pathoplastic, diagnostic/nosological, and
      service management aspects. It is in the psychotherapeutic arena, however, where
      both patient and therapist must face a multitude of culturally determined
      situations that may have a significant impact on the outcome of treatment.
      Culture can help the therapist to dispose of misleading clinical labels, with
      obvious advantages for the patient's well-being. Psychotherapy can correct the
      pathogenic elements of the patient's culture, recognize the pathoplastic clothing
      of the patient's symptoms, and provide culturally sanctioned and valued success
      experiences that may increase self-esteem, strengthen stability and,
      particularly, contribute to the patient's achievement of an identity with which
      he or she can feel comfortable. Finally, it must be remembered that it is not up
      to the therapist to offer infallible explanatory models of the patient's plight,
      but only culturally acceptable premises on which to build such explanations. On
      the other hand, it is up to the therapist to recognize the "idioms of distress,"
      both physical and psychological, that the patient conveys in the
      psychotherapeutic context which is, as had been said many times here, totally
      immersed in the environment of culture. Two vignettes illustrate several of the
      issues under discussion.

PMID- 9656055
TI  - Otto F. Kernberg, M.D., F.A.P.A., developer of object relations psychoanalytic
      therapy for borderline personality disorder. Interview by Lata K. McGinn.

PMID- 9656056
TI  - Treatment of homophobia in a gay male adolescent.
AB  - Gay teenagers experience normal adolescent developmental processes, but need
      assistance negotiating the effect of homophobia on their development. Homophobia
      in the early phase may increase reliance upon the family. This can make it
      difficult to extricate oneself from family sufficiently to develop peer
      relationships. Supportive individual and interpretative family work can help
      modify these problems. Problems in the middle phase are associated with societal
      homophobia in the institutions where adolescents develop. High school social
      dynamics support homophobia and make opportunities to develop a peer network
      difficult. Therapeutic interventions that support a gay teen's efforts through
      fantasy and symbolic action are key to success in to this period. Referral to gay
      teen support groups are more likely to be successful during this phase. During
      the late phase of adolescence, homophobia complicates the quest for an acceptable
      social role and the need for more intimate relationships as plans for work and
      pairing become the focus. The therapist helps the gay teen overcome stereotypes
      and see themselves as individuals and as a members of a group called "gay." This
      makes it possible to integrate personal aspects of the self with gay-group
      identity.

PMID- 9656057
TI  - Reconsidering the transference paradigm in treatment with the bereaved.
AB  - What is to be expected of bereaved people years after a loss? How will life be
      lived following the conclusion of the mourning process? Answers to questions such
      as these are inherent in the use of terms such as recovery following loss or the
      resolution of bereavement. From the perspective of the Two-track Model of
      Bereavement, it should be clear that the outcome of loss needs to be examined
      along the dimension of functioning, where the term recovery might well be
      adequate, and along the dimension of the continuing relationship to the deceased,
      where resolution would be the more precise term. When one considers the impact of
      bereavement upon the individual years following the loss, it is well to keep in
      mind that both recovery and resolution range across the continuum, with varying
      degrees of adjustment, coping, and continued relationship to the representations
      of the deceased neither fixed nor static. In many ways, the continuing
      relationship to the deceased is similar to the relationships we have with living
      individuals. The more comfort and openness characterize the connection to
      memories and thoughts of a particular relationship, the greater the likelihood
      that the relationship is not a focus of conflict or difficulty requiring
      intervention. Changes in the relationship to the deceased will continue across
      the life-cycle. The presence of flexibility and resilience in the internal object
      world are important features of the individual's ability to deal with the ebb and
      flow of a life course.

PMID- 9656058
TI  - An effective analytical psychotherapy in crosscultural context. An East Asian
      student in the United States.
AB  - An effective analytical psychotherapy of a severe anxiety disorder with panic, in
      a crosscultural context of East Asia and the United States, specifically a
      Japanese student studying English, is presented. What was crucial in facilitating
      the therapeutic process was an introduction of analytical way of looking at life
      born of Western culture into an integrative orientation of Asian culture and
      mentality.

PMID- 9656059
TI  - Time-limited group treatment of children.

PMID- 9656060
TI  - [Multiresistant tuberculosis in Spain: threat or fact?].

PMID- 9656061
TI  - [Cough variant asthma. Clinical and functional characteristics. Report of 63
      cases].
AB  - To study the characteristics of our outpatient clinic patients presenting with
      chronic cough as the sole symptom of bronchial asthma, and to evaluate the
      bronchial hyperreactivity of such patients in comparison with that of classic
      asthmatic patients with normal spirometry. For 3 years we studied 193 consecutive
      patients with chronic cough as the sole symptom, using the study protocol
      specified in the section on patients and methods. Sixty-three patients were
      diagnosed of bronchial asthma. Bronchial hyperreactivity was considered to be the
      cause of coughing based on reversibility testing or a positive methacholine test,
      along with response to specific antiasthmatic therapy. Forty-six (73%) of the 63
      patients had unproductive cough and 28 (44%) coughed mainly at night. In 14 (22%)
      symptoms began with an upper respiratory tract infection. Wheezing could be heard
      in only 4 (6%). Diagnosis was based on reversibility in 11 (17%) and methacholine
      testing in 52 (83%). Mean PC20 was higher in patients diagnosed of variant cough.
      Unlike classic asthma, persistent and usually unproductive cough caused by asthma
      has few or no accompanying symptoms. The diagnostic yield of methacholine testing
      is high in such patients.

PMID- 9656062
TI  - [Usefulness of transbronchial punction and mediastinoscopy in mediastinal nodal
      staging of non-microcytic bronchogenic carcinoma. Preliminary study].
AB  - Preliminary study to compare the sensitivity and specificity of transbronchial
      needle aspiration (TBNA) and mediastinoscopy/anterior mediastinotomy (MED/AMED)
      and/or thoracotomy for staging of mediastinal nodes in non-small cell carcinoma.
      To determine the sensitivity and specificity of computerized tomography (CT) as a
      screening technique. Thirty-three patients with non-small cell carcinoma but no
      remote metastasis and good lung function were evaluated. A chest CT scan was
      performed before bronchoscopy in 27 patients and before surgery in the others.
      Nodular areas considered diseased based on CT images were staged by TBNA. When CT
      images were not available before bronchoscopy. TBNA for staging was performed in
      the subcarinal region. Results by TBNA were compared with those obtained by
      MED/AMED and/or thoracotomy. The prevalence of metastatic nodular disease was
      47%. CT detected enlarged mediastinal nodes in 24 patients; the images were
      considered normal in 9 patients. Sensitivity and specificity of CT was 93% and
      54%, respectively, with a positive predictive value (PPV) of 68% and negative
      predictive value (NPV) of 87.5%. The sensitivity and specificity of MED/AMED were
      73% and 100%, respectively; PPV was 100% and NPV was 75%. The sensitivity and
      specificity of TBNA were 36% and 92%, respectively; PPV was 83% and NPV was 57%.
      The pneumothorax with pleural empyema suffered by one patient after MED could
      have been avoided, given that the earlier TBNA was positive. TBNA is a safe,
      useful technique for staging nodes in non-small cell carcinoma. Although the
      sensitivity of TBNA is lower than that of MED, regions that are difficult to
      reach with the latter technique can be sampled by TBNA. Furthermore, MED can be
      rendered unnecessary by positive TBNA results. CT imaging of the chest is
      sensitive but its specificity is low for detecting ganglial metastasis.

PMID- 9656063
TI  - [Symptoms of sleep apnea syndrome in the general population].
AB  - The aim of this study was to determine the clinical features of patients with
      sleep apnea syndrome (SAS) in the general population. One hundred ten individuals
      were selected randomly from the census and given hospital appointments. Case
      histories were taken and complete physical examinations were made. Nighttime
      respiratory polysomnograms were performed. Twenty-two (20%) of the 110 subjects
      presented SAS. In the SAS group, 59.1% were habitual snorers and 22.7% reported
      daytime hypersomnolence. The SAS patients has a mean age of 59.6 +/- 8.8 years
      and 45.4% showed alterations of the pharynx. No differences in spirometric
      variables were observed. Only age and daytime hypersomnolence predicted SAS in
      the multivariate analysis. We conclude that the prevalence of snoring, daytime
      hypersomnolence, pharyngeal alterations are higher in patients with SAS. The
      patients are also older. Only age and daytime hypersomnolence predicted of SAS.

PMID- 9656065
TI  - [Molecular biology in the diagnosis and treatment of respiratory diseases].

PMID- 9656064
TI  - [Results of surgical treatment of non-microcytic bronchopulmonary carcinoma in
      III-A stage].
AB  - To analyze results and survival after surgical treatment of various stage III-a
      subgroups. We reviewed 748 case histories of patients with non-small cell
      bronchopulmonary carcinoma between January 1970 and December 1991, selecting 121
      patients who underwent resection of stage III-a tumors, according to the
      pathologist's report. Overall survival at 3, 5 and 10 years was 26, 16 and 12%,
      respectively. The subgroup with better response to treatment was that of patients
      with T-3 tumors (peripheral), N-0, with survival of 21% at five years. If
      peribronchial and/or hilar (N-1) nodes were affected, survival was slightly less
      (16%). If mediastinal adenopathy (N-2) was present, there were no survivors after
      3 years. In this same T-3 group, but with neoplastic invasion of the pericardium,
      mediastinal pleura or principal bronchi, survival after 3 years was nil. The
      survival rates of peripheral T-3 patients undergoing block resections were 27, 20
      and 17% at 3, 5 and 10 years, respectively, 16% at 2 years and 0% at 5, for those
      with extrapleural resection. Patients with the poorest response to treatment were
      those with mediastinal nodes (N-2), in whom survival was 17, 12 and 8% at 3, 5
      and 10 years, respectively. In the 34 patients received postoperative irradiation
      of the mediastinum, survival was 16% higher. The survival rates after 5 years
      were similar for epidermoid carcinoma (18%) and adenocarcinoma (14%). The results
      of surgical treatment are variable and depend on several factors: extension and
      extrapulmonary location of lesions, surgical technique used for T-3 tumors and
      histological type.

PMID- 9656066
TI  - [Pancoast syndrome caused by lung tuberculosis].
AB  - Pancoast's syndrome arises from neoplasms in 95% of cases but infection is a rare
      cause. We describe a patient with Pancoast's tumor secondary to tuberculosis.
      Pain caused by plexopathy and lack of diagnosis by noninvasive means led to the
      need for open biopsy.

PMID- 9656067
TI  - [Agenesis of the left pulmonary artery in an asymptomatic young woman].

PMID- 9656068
TI  - [Askin's+ tumor in childhood. Considerations after a 2-year follow-up].

PMID- 9656069
TI  - [Bronchial carcinoid: unusual recurrence as probable endobronchial metastasis].

PMID- 9656070
TI  - [Mediastinitis and pleural effusion secondary to parenteral nutrition solution
      extravasation].

PMID- 9656071
TI  - [Malignant pheochromocytoma: one of the causes of lung metastasis with prolonged
      survival].

PMID- 9656072
TI  - [Recurrent mediastinal liposarcoma].

PMID- 9656073
TI  - [Varices of pulmonary veins: infrequent cause of lung nodules].

PMID- 9656074
TI  - [Exacerbation of COPD by Escherichia coli. Antibiotic treatment in exacerbations.
      Should we extend the standard?].

PMID- 9656075
TI  - [Infection of the low airways caused by Neisseria meningitidis and Streptococcus
      pneumoniae in a patient with AIDS].

PMID- 9656076
TI  - [Lung sclerosing hemangioma: cytohistologic inconsistency and clinical
      implications].

PMID- 9656077
TI  - [What is heart failure?].

PMID- 9656078
TI  - [Phenotype and reactivity of T-lymphocytes isolated from atheromatous plaque.
      Knowledge obtained from a transplant case].
AB  - The primary immunologic hypothesis assumes that the initial damage in
      atherosclerotic lesions is mediated by T lymphocytes reactive to heat shock
      proteins, lipoproteins, bacteria, virus or even donor MHC antigens. A frequent
      cause of heart transplant failure is the de novo formation of atheromatous
      lesions in the vessels of the transplanted organ despite their absence in the
      donor, thus suggesting that new lesions are secondary to a cellular immune
      response by the receptor. In this study we determined the phenotype and the
      reactivity of T cells from peripheral blood and from endomyocardial and
      atherectomy biopsies obtained from the same immunosuppressed patient who
      underwent a heart transplant in 1989. A panel of homozygous HLA-typed, Epstein
      Barr virus transformed B lymphocytes were used as stimulators in functional
      assays. Our results showed an important increase in the percentage of CD4+ cells
      in the atheromatous plaque as well as in the endomyocardium, and a considerable
      amount of TCR sigma+ lymphocytes in the atheromatous plaque. A considerable loss
      of alloreactivity to HLA antigens was also observed. These results suggest that
      although there are adequate conditions to mount a cellular immune response a
      state of cellular anergy exists towards HLA antigens probably as result of
      prolonged immunosuppressive therapy. The presence of obstructive lesions in this
      particular patient don't seem to be secondary to HLA alloreactivity but could be
      secondary to a switch in the cellular immune response as a consequence of chronic
      exposure to some donor antigen, thus explaining the increased proportion of TCR
      sigma+T lymphocytes.

PMID- 9656079
TI  - [Coronary stent in acute myocardial infarction].
AB  - From December 1995 to March 1997 fifty patients with acute myocardial infarction,
      had 57 stents implanted. Mean time since the beginning of symptoms to the
      procedure was 3.7 +/- 2.9 hours. Twenty-four stents were implanted "de novo", 17
      for "sub-optimal" results, 5 for threatened closure and eleven for complex
      dissection. The arteries treated with stent were left anterior descending in 42%,
      right coronary in 42%, circumflex in 10%, vein grafts in 4%, intermedial branch
      in 1% and marginal obtuse branch in 1%. Stent used in most of the cases was AVE
      in 67% followed by Palmaz-Schatz, Wiktor, Crown, Gianturco-Roubin and Wallstent.
      Before procedure, coronary flow was TIMI 0 in 66% TIMI 1 in 10% and TIMI 2 in
      24%. After procedure, TIMI 3 coronary flow was achieved in 92% of the arteries
      and other four had "no-reflow" phenomenon. Mean stenosis before procedure was 96%
      +/- 3.1 and after stenting was 1.76% +/- 2.6 with a stent/artery diameter rate of
      1.01. Technical success was 100% and clinical success was achieved in 96% of the
      cases. Two cases were not successfully due to acute thrombotic closure in one
      patient and in another one because of cardiogenic shock after two days of a
      technical successful implantation of stent in LAD artery. There were not
      recurrent ischemic events (CABG, re-infarction or new coronary angioplasty
      procedure). Other two patients died for non-cardiac events (acute pancreatitis in
      one and by septic shock in other). At the time of discharge 96% of patients were
      treated with aspirin and ticlopidine. Major hematoma was evident in only one
      case. At a mean follow-up time of 5.6 months +/- 4.2 in 45 patients showed that
      73% were in functional class I and none of them had re-infarction, death or
      needed a new revascularization. CONCLUSION: Stent implantation in acute
      myocardial infarction is feasible and safe procedure with a low rate of ischemic
      recurrent events.

PMID- 9656080
TI  - [Radiofrequency ablation in the treatment of supraventricular arrhythmias in
      pediatrics. Experience with 203 consecutive patients].
AB  - We report the results of radiofrequency catheter ablation in 203 patients under
      18 years of age with supraventricular tachyarrhythmias between April 1992 and
      June 1997. The presence of an accessory pathway caused the tachyarrhythmia in 181
      patients (89.1%) with a total of 187 accessory pathways; atrioventricular nodal
      reentry caused the arrhythmia in 18 patients (8.8%) and atrial flutter in only 4
      patients (1.9%). We eliminated the accessory pathway in 171 patients (91.4%), 23
      patients showed recurrence of the tachycardia and we had complications in 4
      patients (2.1%). The procedure was successful in the treatment of the
      atrioventricular nodal reentry in the 18 cases, with ablation of the slow pathway
      in 17 cases and in only one patient of the fast pathway, one patient showed total
      A-V block, and recurrence of the arrhythmia in 3 cases (16.6%). Finally the
      procedure was successful in the 4 cases of atrial flutter with one recurrence
      (25%). In the total of the series, the radiofrequency catheter ablation was
      successful in 193 patients (95%), with recurrence of the arrhythmia in 27 cases
      (13.3%) and with complications in only 5 patients (2.6%). Radiofrequency catheter
      ablation is a safe and effective procedure for the definitive treatment of
      supraventricular tachyarrhythmias in children.

PMID- 9656081
TI  - [Estimation of cardiac vagal reserve by dynamic exercise in patients with recent
      myocardial infarction].
AB  - In patients with coronary artery disease, the risk of sudden death is related to
      the degree of left ventricular dysfunction and to cardiac parasympathetic
      activity. The relation between these two consequences of myocardial infarction is
      still the matter of intense controversy. In this investigation, we have estimated
      the resting cardiac parasympathetic tone and assessed the left ventricular
      systolic function of 25 patients who had suffered an acute myocardial infarction.
      The absolute increase in heart rate recorded in the first 10 seconds of a
      programmed dynamic exercise, was considered as the resting cardiac
      parasympathetic tone or cardiac parasympathetic reserve. Twenty five age and sex
      matched normal sedentary subjects were used as controls. Patients showed a
      significantly smaller increase in their heart rate (16 +/- 4 lats/min, M +/- DS)
      than the controls 32 +/- 5 P < 0.0001), during the first 10 seconds of exercise.
      Moreover, the absolute increase in heart rate was inversely related to the degree
      of left ventricular dilatation ( r = - 0.71, P < 0.0001) and directly related to
      the left ventricular ejection fraction (r = 0.84, P < 0.0001). In other words,
      those patients with larger left ventricles and depressed ventricular function had
      a more prominent reduction of their resting cardiac parasympathetic tone. These
      results indirectly suggest that, left ventricular size and function are indeed
      related to cardiac parasympathetic activity.

PMID- 9656082
TI  - [Prevalence of carotid atherosclerosis in a cohort of Mexico City].
AB  - In order to investigate the prevalence of atherosclerosis in Mexico, high
      resolution ultrasound and color Doppler flow imaging of carotid arteries were
      carried out in a group of participants in CUPA project, a cohort study started in
      1989 among persons 60 years and older living permanently in a high rise in Mexico
      City. Imaging studies included identification of 4 atherosclerosis related
      abnormalities: 1) intima media thickness; 2) kinkings and tortuousness; 3) non
      stenosing plaques; and 4) significant carotid stenosis (> 50%). Analysis of 198
      Doppler ultrasonographic studies in 56 males and 142 females showed an overall
      prevalence of atherosclerosis related lesions of 65.6%, with increasing frequency
      by age groups: 33% in younger than 65 year-old, 71% in 65-74 years, and up to 88%
      in the 75 years and older group. The prevalence of high grade stenosis was low
      (6%) whereas the overall frequency of non-stenosing plaques and intima-media
      thickness was higher than 60%. Intima-media thickness was more common in males
      while non-stenosing plaques and high grade stenosis were more frequent in
      females. However, there were not significant differences among women and men when
      atherosclerotic lesions were analyzed by age groups. This is the first report on
      the prevalence of atherosclerosis in a Mexican population using ultrasonography.
      Findings of the investigation document the high prevalence of atherosclerosis
      among elderly resident in Mexico City.

PMID- 9656083
TI  - [Vector electrocardiographic findings in chronic Chagas cardiomyopathy].
AB  - Dilated Cardiomyopathy (DCM) is associated with many diseases. By means of
      epidemiologic, clinical and invasive diagnostic techniques, the etiology of DCM
      is identified almost in 50% of the cases. Chronic infection with Trypanosoma
      cruzi is recognized as a cause of DCM in Latin America. A blind study of 40 cases
      of DCM explores the electrovectorcardiographic data obtained in chronic chagasic
      cardiomyopathy (CCC). Twenty one of 40 patients fulfilled epidemiologic and
      seroimmunologic criteria for CCC, 19 had DCM. There were not differences between
      these groups in regard to sex or age. Patients suffering DCM had in addition
      diabetes mellitus, systemic hypertension or ischemic heart disease. Those with
      CCC had not comorbid diseases in 50% of the cases. Arrhythmias and conduction
      blocks were equally recognized in both groups, as well as ECG evidence of injury
      or necrosis (p > 0.05). However, ECG signs of subepicardial ischemia were a
      dominant feature in patients with CCC and normal epicardial coronary arteries (p
      < 0.05). Probably this finding is due to a small vessels damage, a pathogenic
      mechanism proposed in CCC.

PMID- 9656084
TI  - [Preoperative evaluation of severe aortic stenosis by Doppler echocardiography
      and hemodynamics].
AB  - Several diagnostic tools have been used in the evaluation of the severity
      transvalvular gradient and aortic valve area. The advances in cardiac
      catheterization and Doppler echocardiographic measure these items accurately. We
      designed a retrospective, observational open and transversal survey that included
      patients with severe aortic stenosis that required transseptal cardiac
      catheterization. Their echocardiographic and hemodynamic studies were reviewed.
      From January 1991 to December 1996 we studied 30 patient from a population of
      256. All of them with severe aortic stenosis. There were 17 males and 13 females
      with an age range from 32 a 71 years. RESULTS: the transvalvular gradient
      measured by catheterization vs. Doppler echocardiogram was 98.80 +/- 37.29 mmHg
      vs. 96.63 +/- 38.64 mmHg respectively P = 0.84. The valvular area measured by
      catheterization vs Doppler echocardiographic 0.63 +/- 0.17 cm2 vs 0.62 +/- 0.15
      cm2 respectively P = 0.63. There was not difference in the gradients using these
      two methods. We conclude that patients with severe aortic stenosis could be
      referred to surgical procedure without the need of cardiac catheterization if no
      concurrent coronary disease is suspected.

PMID- 9656085
TI  - [Cardiac tamponade in newborn infants with central venous catheter receiving
      parenteral nutrition].
AB  - OBJECTIVE: To alert about an unusual and poorly informed entity, with high
      mortality. That should be considered in critically ill neonates with central
      venous catheter and parenteral nutrition, in order to establish early diagnosis
      and treatment. CASE REPORT: Two neonates, one born at term and the other
      premature, with central venous catheter and parenteral nutrition. They had sudden
      unexplained hypotension and signs of decompensation and death secondary to
      cardiac tamponade. DISCUSSION: Cardiac tamponade secondary to central venous
      catheter is an unusual entity seldom discussed in the literature. The estimated
      incidence is 0.3 to 2% with a 74 to 100% mortality. It must be suspected and
      diagnosed early in order to decrease the mortality.

PMID- 9656086
TI  - Low molecular weight heparins in clinical practice: unsolved or partially solved
      problems.
AB  - Low molecular weight heparins (LMWH) have been shown, in recent years, to be at
      least as effective as standard heparin (SH) in the prophylaxis and treatment of
      venous thrombosis. In spite of several studies there are still some unsolved
      problems to be dealt with. These may be summarized along the following lines: 1)
      Side effect; 2) Use in pregnancy; 3) Role in arterial thrombosis; 4) Use in
      severe deep venous thrombosis; 5) Use for home treatment; 6) Effect on cancer
      related mortality; 7) Standardization of preparations; 8) Dosage uncertainties;
      9) Long term treatment. The two most important aspects are those pertaining to
      the potential use in arterial thrombosis and the possibility of home treatment of
      selected patients with venous thromboembolism. A few studies now indicate that
      LMWH may play an important role in several arterial thrombosis (coronary disease,
      ischemic stroke, etc). As far as the indications for home treatment are
      concerned, recent studies have given a positive answer. However, rather than home
      treatment it would be more appropriate to refer to early discharge from the
      hospital. The overall impression is that LMWH may represent an important progress
      in the management and prophylaxis of thrombotic disease.

PMID- 9656087
TI  - [Methodology in clinical research: its role in medical education].

PMID- 9656089
TI  - Computer-administered rating scales for social anxiety in a clinical drug trial.
AB  - Computer-administered versions of two clinician-administered symptom rating
      scales for social anxiety (the Liebowitz Social Anxiety Scale [LSAS] and the
      Brief Social Phobia Scale [BSPS]) and one paper-and-pencil scale (the Fear
      Questionnaire) were developed and utilized in a clinical trial for social phobia.
      The reliability and validity of the computer versions were examined, as were
      their equivalence to the traditional versions. Correlations between the computer
      and original versions were high at baseline, and remained high throughout the
      study. The internal consistency reliability of the computer scales was also high,
      and almost identical to the original versions. Mean score differences between
      computer and original versions were not significant at baseline, and no
      significant differences were found between computer and traditional versions on
      the amount of change detected from baseline to endpoint. Seventy-seven percent of
      subjects felt that the computer did not interfere with their visit at baseline
      and a plurality (36%) preferred the computer, with 30% preferring the clinician
      and 34% having no preference. By the end of the study, the plurality (41%) had no
      preference, with 27% preferring the computer and 32% preferring the clinician.
      Results support the use of these computer-administered symptom rating scales of
      social anxiety as a viable alternative to the clinician-administered versions
      with this subset of patients, which should offer researchers and clinicians a
      reliable and cost-effective method for evaluating social phobia.

PMID- 9656088
TI  - [William Osler and angina pectoris: still prevailing concepts].

PMID- 9656090
TI  - Simple phobia as a comorbid anxiety disorder.
AB  - This study sought to describe clinical and demographic characteristics
      differentiating patients with DSM-III-R simple phobias comorbid with one or more
      of five DSM-III-R index anxiety disorders as compared with those with the index
      diagnoses alone. From 711 subjects participating in a multicenter, longitudinal,
      naturalistic study of anxiety disorders, 115 subjects with comorbid simple
      phobias were compared with 596 subjects without simple phobias in terms of
      demographic data, comorbidity with other disorders, somatic and psychosocial
      treatment received, and quality of life. In addition, episode characteristics,
      types of simple phobias found, and course of illness were specified. Subjects
      with simple phobias had more additional comorbid anxiety disorders by history
      than did those without. Mean length of intake episode was 22.43 years and
      severity was typically moderate. Fears of heights and animals were the most
      commonly represented simple phobias. Subjects with uncomplicated panic disorder
      were less likely to have comorbid simple phobias than were subjects with other
      index diagnoses, and subjects with simple phobia were more likely to have
      comorbid posttraumatic stress disorder than were these without simple phobia.
      Subjects with and without simple phobias did not differ by somatic or
      psychosocial treatment received or in terms of quality of life. Simple phobia
      appeared in this study to be a chronic illness of moderate severity for which
      behavioral treatment methods of recognized efficacy were not being frequently
      utilized. Uncomplicated panic disorder may reflect some type of resistance to
      phobia development.

PMID- 9656091
TI  - Lifetime patterns of social phobia: a retrospective study of the course of social
      phobia in a nonclinical population.
AB  - This study describes the natural course of social phobia as recalled by a sample
      of nonclinical subjects and explores, using qualitative research methods,
      perceived risk factors and factors that may cause changes in its course. Thirty
      nine respondents with a lifetime diagnosis of social phobia were interviewed
      using a semistructured interview schedule based on DSM-IV criteria. Four main
      lifetime patterns emerged: a slight worsening of social phobic symptoms over
      time, no change, slight improvement and complete remission. Thirty-eight percent
      of the sample was in remission at the time of interview. The mean age of onset
      was 12.8 +/- 4.1 years. The average duration of illness was 29.0 +/- 12.7 years.
      Factors perceived by respondents to precipitate social phobia, using contract
      analysis, were family and school environment, onset of adolescence, low self
      esteem, temperament and poverty. Factors perceived to improve symptoms were
      building self-esteem, exposure, determination, maturity and counseling. Factors
      perceived to worsen symptoms were avoidance, exposure to negative attention and
      comorbid disorders.

PMID- 9656092
TI  - Comparison of sodium lactate-induced panic symptoms between panic disorder and
      posttraumatic stress disorder.

PMID- 9656093
TI  - Low dose selegiline (L-Deprenyl) in social phobia.

PMID- 9656094
TI  - Caffeine use and plasma concentrations in psychiatric outpatients.

PMID- 9656095
TI  - Medication treatments for panic disorder and social phobia.
AB  - In this Research Review, several recent clinical trials in panic disorder and
      social phobia are reviewed. First, two social phobia studies which used the
      monoamine oxidase type A inhibitors brofaromine and moclobemide are considered.
      Then, three panic disorder studies which used clonazepam, clomipramine or
      paroxetine, and citalopram are examined. These studies serve to strengthen the
      empirical research base regarding which treatments are useful in these disorders.

PMID- 9656096
TI  - Intrusive thought in obsessive-compulsive disorder: appraisal differences.

PMID- 9656097
TI  - Working on the railroad: reactions to traumatic and stressful events.

PMID- 9656098
TI  - Possible inhibition of family PTSD symptoms by alcohol intoxication.

PMID- 9656099
TI  - [Advanced prostate cancer with normal serum prostate-specific antigen values].
AB  - Although prostate-specific antigen (PSA) is a valuable marker of prostate cancer,
      some untreated patients with advanced prostate cancer have normal PSA values.
      Over a period of 5 years, we reviewed pretreatment serum PSA levels in 131
      patients with advanced prostate cancer (stages C and D). Ten patients (7.6%) had
      normal PSA values. The histological type of prostate cancer associated with
      normal PSA values was variable and the prognosis was not so poor. Immunostaining
      for PSA was performed on the resected prostate tissue of the 10 patients. PSA
      staining was positive in 5 cases, negative in 3 cases, and equivocal in the
      remaining 2 cases. In conclusion, PSA is not always useful, especially for
      following patients with normal PSA values.

PMID- 9656100
TI  - Free-to-total prostate specific antigen ratio in clinical staging of prostate
      cancer.
AB  - The value of the free-to-total serum prostate-specific antigen (f/t PSA) ratio
      was compared with that of the total prostate specific antigen (tPSA) value for
      the prediction of clinical stage in patients with prostate cancer. The f/t PSA
      ratio was obtained from the frozen sera of 56 untreated patients with
      histologically proven BPH and 78 patients with prostate cancer. The clinical
      stage was organ-confined in 36, locally advanced in 20 and metastatic in 22
      patients. Serum levels of free PSA (fPSA) and tPSA were determined using a
      chemiluminescent enzyme immunoassay. The f/t PSA ratio was calculated by dividing
      the fPSA value by the tPSA value and was compared with tPSA and fPSA in the
      correlation with clinical stage via the Spearman rank correlation test. Patients
      with prostate cancer had a significantly lower f/t PSA ratio than patients with
      BPH. The f/t PSA ratio did not differ between patients with clinically localized
      and metastatic cancer. tPSA and fPSA reflected the clinical stage and the extent
      of bone metastasis more accurately than the f/t PSA ratio. The extent of bone
      metastasis had no effect on the PSA ratio. The f/t PSA ratio had no additional
      value in clinical staging compared to tPSA. Our study suggests that the f/t PSA
      ratio does not reflect tumor load.

PMID- 9656102
TI  - [A case of renal cell carcinoma with metastasis in clivus presenting as
      diplopia].
AB  - We report a rare case of renal cell carcinoma presenting as diplopia which was
      caused by a metastasis to the clivus. A 58-year-old man was admitted to our
      hospital with the chief complaint of diplopia. Head magnetic resonance imaging
      showed a mass in the clivus accompanied by bone destruction. Metastatic tumor to
      the skull base was suspected. Further examinations for the primary lesion
      revealed left renal cell carcinoma. He was relieved of diplopia by radiotherapy
      to the clivus and subsequently underwent left radical nephrectomy.

PMID- 9656101
TI  - [High dose chemotherapy with peripheral blood stem cell transplantation (PBSCT)
      For advanced testicular cancer].
AB  - Five patients with metastatic testicular cancer of advanced extent according to
      the Indiana University criteria were enrolled into this study. All tumors were
      non-pretreated non-seminomas. Initially all patients were treated with standard
      dose etoposide, ifosfamide and cisplatin (VIP) regimen. The response of two
      cycles of VIP was evaluated by tumor markers and diagnostic imagings. Two of the
      five patients showed a good response to VIP and subsequently achieved a
      pathological complete response (pCR) following surgical resection of residual
      masses after 3 or 5 courses of VIP. However, they suffered from severe
      myelosuppression and underwent peripheral blood stem cell transplantation (PBSCT)
      following the final course of VIP. The remaining three patients unlikely to be
      cured by VIP underwent chemotherapy consisting of high dose ICE:ifosfamide (6-10
      g/m2 over 4days) carboplatin (1,500 mg/m2 over 4 days), etoposide (1,600-2,400
      mg/m2 over 4 days) combined with PBSCT. This regimen resulted in one partial
      response (PR) with marker-negative and two PR with marker-positive. Residual
      masses were removed in all three patients and viable tumor cells were found in
      two. Of the five patients enrolled, four patients (80%) remain disease-free with
      minimal follow-up of 20 months, and the remaining one died of cancer 10 months
      after PBSCT. No serious side effects or complications were encountered. This
      study shows that standard dose induction therapy of VIP followed by early salvage
      chemotherapy of high dose ICE with PBSCT is well tolerated and effective in the
      treatment of advanced poor-risk testicular cancer.

PMID- 9656103
TI  - [Laparoscopic fenestration of lymphocele after renal transplantation: report of
      two cases].
AB  - Lymphocele after renal transplantation is a complication that often requires
      surgical treatment. We performed laparoscopic drainage for the postoperative
      lymphocele in two renal transplantation patients. The patients were suffering
      from perineal discomfort and urinary frequency due to the lymphocele after the
      renal transplantation. Percutaneous catheter drainages and injections of tissue
      sclerosing agents such as povidone-iodine solution and tetracycline were not
      effective. Then fenestration of the lymphocele by laparoscopic technique was
      done. This procedure made the lymphatic fluid free from the lymphocele in the
      retroperitoneal space to the peritoneal cavity following creation of a peritoneal
      window. There were no apparent complications. The patients were free from
      symptoms and had no relapse 10 months after the operation. We report the
      procedure and the results of the laparoscopic fenestration.

PMID- 9656104
TI  - [Successful treatment with end-to-end ureteral anastomosis for ureteral avulsion
      caused by abdominal blunt trauma: a case report].
AB  - Avulsion of ureter without renal injury is rarely caused by blunt trauma, only 28
      cases having been reported in Japan. A 33-year-old male was admitted to our
      hospital 1 month after blunt abdominal trauma at work. He complained of left
      flank pain and macroscopic hematuria. Under the suspicion of renal or ureteral
      injury, drip infusion urography and abdominal computerized tomography revealed an
      extravasation from the left upper ureter and urinoma formation in the
      retroperitoneal cavity. In order to reduce the inflammation, the urinoma was
      drained. The retrograde pyelogram revealed complete obstruction at the left upper
      ureter, 20 cm from the left ureteral orifice. Urinary tract reconstruction, end
      to-end ureteral anastomosis, was performed under the diagnosis of left ureteral
      avulsion. Drip infusion urography revealed normal ureteral healing without
      stricture formation at 2 years after reconstruction.

PMID- 9656105
TI  - [Retrovesical leiomyoma: a case report].
AB  - A 41-year-old woman was admitted to our hospital with the chief complaint of
      difficulty of urination during the previous 2 years. Physical examinations
      revealed a smooth round mass of about 6 cm in diameter at the vaginal anterior
      wall. DIP and MRI showed a retrovesical tumor which was composed of benign
      leiomyoma, according to the transvaginal needle biopsy report. The retrovesical
      tumor was excised by the transvaginal approach. The tumor, 7 x 6 x 4 cm in size
      and 109 g in weight, was histologically diagnosed as leiomyoma. This is the 21st
      case of retrovesical leiomyoma reported in the literature in Japan.

PMID- 9656106
TI  - [A case of endometrioid carcinoma of the prostate].
AB  - A case of endometrioid carcinoma of the prostate is reported. A 64-year-old man
      was admitted to our department with initial macrohematuria and dysuria. The
      transrectal ultrasonogram showed remarkable prostatic hypertrophy and the serum
      level of both prostatic specific antigen (PSA) and prostatic acid phosphatase
      (PAP) ranged within normal limits. Urethrocystographical and cystoscopical
      findings indicated prostatic hypertrophy with elongation of prostatic urethra and
      mild trabeculation of bladder wall. During transurethral resection of the
      prostate, papillary tumor was accidentally found in the left lobe near the
      vermontanum. Histopathological examination revealed adenocarcinoma of the
      prostatic urethra and the tumor displayed no immunoreactivity for PSA or PAP.
      Under diagnosis of prostatic urethral cancer total cystoprostatectomy and
      urethrectomy were performed and ileal conduit was constructed for urinary
      diversion. As intraductal papillae and complex ramifying glands were
      histopathologically confirmed in the specimen and the immunohistochemical
      staining showed positivity of PSA and PAP, the tumor was diagnosed as
      endometrioid carcinoma of the prostate.

PMID- 9656107
TI  - [The impact of rejection episodes during acute tubular necrosis--diagnosis and
      allograft outcome after cadaveric renal transplants].
AB  - Diagnosis of acute rejection (AR) is difficult during acute tubular necrosis
      (ATN), and a delay of rejection treatment could result in negative impacts on the
      renal transplant outcome. At our center, 68 cadaveric kidneys were transplanted
      during the past 7 years. The 1-, 3- and 5-year graft survival rates were 95.4%,
      93.8% and 81.4%, respectively. After the transplants, 16 patients had immediate
      graft function (G-I), 51 patients experienced ATN for 12.0 +/- 9.3 days, and one
      patient had a non-functioning graft due to diffuse arteriolar thrombosis caused
      by DIC in the donor. During ATN, 41 patients had no rejection episodes (G-II) and
      10 patients had ARs (G-III). Nine patients were treated with bolus steroid and
      one with steroid and OKT-3. Although scintigraphic and sonographic examinations
      were routinely employed, only the histopathological findings of needle biopsies
      were helpful for the diagnosis of AR during ATN. When the transplant outcome was
      compared, the serum creatinene level was highest in G-III and lowest in G-I (1.48
      vs 1.06 mg/dl, p < 0.05). The posttransplant ATN period was also longer in G-III
      compared to G-II (23.9 vs 9.1 days, p < 0.005). The 5-year graft survival rate
      was 85.2% in G-I, 88.0% in G-II and 59.3% in G-III. We conclude that routine
      serial renal biopsies should be scheduled when ATN develops after the cadaveric
      renal transplant, since only the histopathological diagnosis is reliable during
      ATN.

PMID- 9656108
TI  - [The treatment and prognosis of acute late rejection after kidney
      transplantation].
AB  - To examine the acute late rejection episodes (ALR) occurring 4 months after
      kidney transplantation, 330 cadaver kidney transplant recipients who were
      operated on between 1982 and 1996 and immunosuppressed by cyclosporine or
      tacrolimus were analyzed. In 213 recipients who were followed up for 5 years or
      longer, the frequency of ALR without an acute early rejection (AER) was 14% and
      ALR with AER was 16%, respectively. ALR was the strongest deteriorating factor
      for graft survival at the chronic stage. Judging from the renal function 1 month
      after an ALR episode, the complete and partial response rates were 22% and 62%
      with steroid treatment and 16% and 58% with DSG treatment, respectively. The 5
      year graft survival after the treatment was 20% with steroid treatment and 45%
      with DSG treatment. Although the intensity of the rejection classified based on
      the Banff grading system was the strongest factor affecting the graft survival,
      the multivariate analysis by Cox proportional hazard model for non-pathological
      factors revealed that urine protein and hypertension 1 month before the episodes
      may also be important prognostic factors. The body weight of recipient (> 55 kg)
      and donor age (> 55 y.o) were slightly correlated to the graft prognosis. Due to
      incomplete immuno-suppressive methods for acute late rejection, the conservative
      nephron sparing policy after a rejection episode is inevitable to obtain better
      graft survival at the chronic stage.

PMID- 9656109
TI  - [Current topics of the rejection pathology in human renal allografts].
AB  - The topics of renal allograft pathology; validation of the Banff classification
      and a new criterion for chronic rejection are reviewed. Although the clinico
      pathologic utility of the Banff classification is remarkably high in acute
      rejection, the Banff scheme is still incomplete. The severity of rejection based
      on the Banff schema well correlated with the deterioration of graft function and
      also with reversibility of the graft function. Grade III acute rejection in the
      Banff schema suggested poor graft function, while grade IIb acute rejection could
      be cured by rejection therapy in the CyA era. The morphological characteristics
      of chronic rejections in renal allografts become milder and less specific in the
      CyA era. The differentiation of chronic rejection of immunologic origin from
      other conditions leading to renal scarring remains one of the major problems in
      renal allograft biopsy interpretation. Chronic CyA nephrotoxicity and/or
      glomerulonephritis frequently accompany chronic rejection. Electron microscopic
      peritubular capillary basement membrane lesion (MSPTC) was a sensitive indicator
      for chronic rejection of immunologic origin as well as glomerular capillary
      lesions. The negative MSPTC in the patients with chronic rejection suggest that
      the deterioration of the graft function is probably non-immunologic in origin.

PMID- 9656110
TI  - [Indication for the steroid therapy for acute rejection].
AB  - Between January 1, 1986 and March 31, 1997, 103 kidney transplantations were
      performed at our institution. Seventy-nine grafts were from living related
      donors; one was from a living unrelated donor; 23 were from cadaveric donors.
      Basic immunosuppression consisted of cyclosporin (CYA), azathioprine (AZ) and
      methylprednisolone (MP). Twenty of these grafts (14.9%) developed steroid
      resistant rejection (SRR). The 5-year graft survival rate of patients with SRR
      (57.9%) was lower than that with no rejection (92.9%) and steroid responded
      rejection ( 85.6%). (p = 0.002) Treatment methods of SRR were methylprednisolone
      pulse (n = 5), plasma exchange (n = 7) and others (n = 8) such as, OKT 3, 15
      deoxyspergualin, anti-thymocyte globulin, Tacrolimus rescue and cyclosporin
      rescue. No significant differences could be seen on the 5-year graft survival
      between the 3 groups. We reviewed 9 episodes of acute rejection, and compared the
      Banff classification with the degree of reversibility of rejection. Of the 9
      biopsies examined, 5 were classified as borderline change, 2 had mild rejection
      (grade I), 2 had moderate rejection (grade II), 1 had severe rejection (grade
      III). Complete reversal of rejection by steroids was observed in only 3 patients;
      2 were borderline and one was grade II.

PMID- 9656111
TI  - [Histopathological findings and clinical effects for acute rejections].
AB  - We reviewed 115 cases of acute rejection following renal transplantation. All
      cases were diagnosed after graft biopsy, and showed histopathological evidence of
      acute rejection. They were treated with administration of OKT3, 15
      deoxyspergualin (DSG), anti-lymphocyte globulin (ALG) or methylprednisolone (MP).
      All rejections were histopathologically classified according to the Banff working
      classification. The clinical effects of each drug were evaluated both at 1 month
      and 1 year following the therapy for rejection, by measurement of serum
      creatinine level. The effective rate both at 1 month and 1 year was related with
      the Banff working classification ( p < 0.0001). At 1 month after treatment, there
      were no significant differences between the OKT3, DSG or ALG group and MP group
      in cases of borderline change and AR grade I. In cases of grade II and grade III,
      a significant difference was observed between the OKT3 or ALG group and MP group
      (p < 0.05). The DSG group showed a slightly better outcome than the MP group,
      although the difference was not significant. In conclusion, the Banff schema is
      shown to be valid for classification of acute renal allograft rejection, and it
      is necessary to determine the treatment for acute rejection according to
      histopathological classification.

PMID- 9656112
TI  - [Is tacrolimus effective for ongoing renal allograft rejection?].
AB  - Tacrolimus has already gained a high reputation as an induction-maintenance
      immunosuppressive therapy after kidney transplantation. Recently, it is being
      used as rescue therapy against rejection, and its effectiveness also appears to
      have been established to some extent. In this study, we evaluated the efficacy of
      Tacrolimus rescue therapy at 4 institutions in the Kinki District. The subjects
      were 19 patients treated with Tacrolimus against rejection observed during
      immunosuppressive therapy using cyclosporin. Evaluation was made by classifying
      the patients into 6 with acute rejection that occurred within 3 months after
      transplantation (AR), 4 with late onset acute rejection that developed more than
      3 months after operation (LAR), and 9 patients with chronic rejection (CR). In
      the AR group, many patients received combination therapy at the introduction of
      Tacrolimus, and the long-term outcome was satisfactory. Tacrolimus was effective
      in 2 (50%) of the 4 patients in the LAR group. The trough levels of Tacrolimus at
      its introduction were 10-15 ng/ml in the AR and LAR groups. Deterioration of the
      transplanted kidney function was prevented in 3 (50%) out of 6 patients in the CR
      group observed for less than 1 year, but it deteriorated in all 3 patients
      observed for 1 year or longer. The trough levels of tacrolimus at its
      introduction were 5-10 ng/ml in many patients in the CR group. The rescue therapy
      using Tacrolimus was effective against acute rejection but further follow-up is
      considered to be needed to evaluate its efficacy against chronic rejection.

PMID- 9656113
TI  - Isolated necrotizing arteritis of the female genital tract: a clinicopathologic
      and immunohistochemical study of 11 cases.
AB  - Isolated necrotizing arteritis (INA) of the polyarteritis-nodosa type localized
      to the female genital tract is rare. Approximately 30 case reports have been
      published to date. Eleven additional patients are described here, all with a
      favorable follow-up. INA is usually localized in the uterine cervix, but, when
      multifocal lesions are present, the latter is almost always involved. Patients
      most frequently report menorrhagia or postmenopausal bleeding. With
      immunohistochemical studies, immune-complex deposits (IgM, IgG, and C'3) in 7 of
      11 patients with INA of the female genital tract were demonstrated for the first
      time. The inflammatory cells were composed mainly of T-lymphocytes with
      macrophages and scarce B-lymphocytes also present. These results suggest that INA
      is primarily an immune complex-mediated disease, implicating humoral and cellular
      mediator systems. Possible pathogenetic factors of INA are immune complex
      mediated hypersensitivity reactions to drugs, foreign materials (after cone
      biopsy or curettage), and cancers, or an autoimmune reaction against constituents
      of the vessel walls caused by tissue injury after local surgical intervention
      through in situ immune-complex formation.

PMID- 9656114
TI  - Do mucin-secreting squamous cell carcinomas of the uterine cervix metastasize
      more frequently to pelvic lymph nodes? A case-control study?
AB  - Twenty-nine patients with stage IB/IIA squamous cell carcinoma of the uterine
      cervix who had positive pelvic nodes were matched with 29 cases of node-negative
      squamous cell carcinoma by depth of invasion and lymphovascular space invasion.
      By multivariate analysis, these criteria independently predicted pelvic node
      metastases. Intracellular mucin, demonstrated by alcian-blue staining at pH 2.5,
      was noted in 21 of the 58 patients (36%). The frequency of mucin-positive tumors
      was not significantly different between the patients and their controls (38
      versus 34%, p = 0.78), nor was the degree of positivity. These results suggest
      that, although a substantial proportion of squamous cell carcinomas exhibit mucin
      secretion, patients with these tumors are not at increased risk for pelvic node
      metastases. We therefore do not recommend routine mucin staining in cervical
      squamous cell carcinomas.

PMID- 9656115
TI  - Ulex Europaeus lectin and anti-CD31 staining in squamous cell carcinoma of the
      uterine cervix: potential prognostic markers.
AB  - Seventy-five squamous cell carcinomas of the uterine cervix and 10 controls were
      stained for Ulex Europaeus lectin 1 (UEA-1) and anti-CD31, and the results were
      analyzed with respect to patient age, clinical stage, tumor grade, and survival
      during a follow-up period of 1 to 13 years. The patients' mean age at the time of
      diagnosis was 47.8 years (range, 27 to 83). Seventeen patients died of disease, 2
      had disease recurrence, and 51 patients remained free of disease; 5 patients were
      lost to follow-up. Twenty-eight cases (37.3%) showed focal membranous staining
      for UEA-1 and 9 cases (12%) showed a diffuse pattern; 38 cases (50.7%) were UEA-1
      negative. Poor survival was related to diffuse membranous UEA-1 immunoreactivity
      (p = 0.02), age (p = 0.014), grade (p = 0.02), and stage (p = 0.0002). CD31
      positive neoplastic cells displayed a cytoplasmic pattern. Fifteen cases (20%)
      had diffuse staining and another 15 (20%) stained focally; 45 cases (60%) were
      CD31-negative. The adjacent nonneoplastic epithelium and all 10 controls were
      uniformly negative for CD31. Variable staining of the endocervical epithelium and
      weak or negative staining of ectocervical epithelium for UEA-1 were observed.
      However, the epithelium in all controls was negative for UEA-1. Poor survival was
      related to both focal and diffuse staining for CD31 (p = 0.01 and p = 0.03,
      respectively). Staining by both UEA-1 and anti-CD31 retained its correlation with
      survival after exclusion of stage la tumors.

PMID- 9656116
TI  - Malignant mullerian mixed tumors of the uterine cervix: a report of nine cases of
      a neoplasm with morphology often different from its counterpart in the corpus.
AB  - Malignant mullerian mixed tumors (MMMTs) of the uterine cervix are rare; less
      than 30 cases have been reported in the literature and only 14 have been
      described in detail. As a result, the clinical and pathologic features of these
      tumors are not well characterized. The clinicopathologic features of nine
      cervical MMMTs (all cases referred because of problems in differential diagnosis)
      are reported here and the literature on the previously described cases is
      reviewed. The patients ranged in age from 23 to 87 (mean 65) years. The initial
      manifestations were mainly vaginal bleeding or spotting or, less commonly, an
      abnormal Pap smear. All of the patients had a cervical mass on examination. Of
      the eight patients for whom staging information was available, seven were stage
      Ib and one was stage II. Treatment in six patients was hysterectomy with
      lymphadenectomy in five; postoperative radiation therapy, chemotherapy, or both
      were given to two of these patients. The remaining three patients were treated by
      local excision (with lymphadenectomy in one) followed by radiation therapy,
      chemotherapy, or both in two. Follow-up, available for seven patients, revealed
      recurrent pelvic tumor in two patients at 1.6 and 3.0 years, respectively; the
      former patient died from tumor at 3.5 years whereas the latter was alive with
      tumor at 4.5 years. Another patient was well for II years but died 13 years
      postoperatively from colonic adenocarcinoma. Four other patients were alive with
      no evidence of tumor at postoperative intervals of less than 2 years. Gross
      examination revealed polypoid or pedunculated masses 1.1 to 10.0 cm in maximal
      dimension that invaded the cervical wall in 50% of the hysterectomy specimens. On
      microscopic examination, three tumors contained a predominant or exclusive
      epithelial component of basaloid carcinoma, two contained squamous cell
      carcinoma, and four contained adenocarcinoma (endometrioid in three and
      nonspecific in one). In seven tumors, the sarcomatous component was homologous,
      usually resembling fibrosarcoma or endometrial stromal sarcoma; in four of these
      tumors, myxoid change was prominent. Two tumors contained heterologous
      sarcomatous elements. In three patients, a pure carcinoma abutted the MMMT: an
      adenoid basal carcinoma in two (with a minor component of in situ and invasive
      squamous cell carcinoma in each) and an endometrioid endocervical adenocarcinoma
      in one. These findings, combined with analysis of the previously reported cases,
      indicate that cervical MMMTs, compared to their counterparts in the corpus, are
      more commonly confined to the uterus at presentation, may have a better
      prognosis, and frequently have a nonglandular epithelial component.

PMID- 9656117
TI  - Malignant schwannoma of the uterine cervix: a study of three cases.
AB  - Pure sarcomas of the uterine cervix are rare; most of those reported have been
      leiomyosarcomas or rhabdomyosarcomas. Minimal data exists on malignant nerve
      sheath tumors in this site; only one typical example and one melanocytic example
      have been reported. We report three additional examples here in three patients
      25, 65, and 73 years of age. The two older patients had vaginal bleeding and
      underwent hysterectomy as initial treatment. The youngest patient initially
      underwent only polypectomy. The tumors were 1.3, 4.4, and 5.0 cm in greatest
      dimension. The tumors were red-grey to white: two were polypoid and the third was
      ulcerated. The dominant microscopic appearance was that of cellular fascicles of
      spindle cells with hyperchromatic nuclei and eosinophilic cytoplasm. However,
      hypocellular areas were striking in each case; the hypocellular areas were
      fibromatous in two tumors and two had areas with a myxoid stroma (prominent in
      one). One tumor focally had cellular aggregates with a swirling pattern within a
      hypocellular background. Epithelioid foci in which tumor cells were rounded with
      conspicuous eosinophilic cytoplasm were focally prominent in one case. Mitoses
      were readily identified in each case. All three tumors were positive for S-100
      protein and vimentin and negative for cytokeratin. HMB-45, and desmin. One case
      is recent and one patient had multiple metastases in the abdomen 2 years after
      hysterectomy. The patient treated initially by polypectomy underwent repeat local
      excision, followed by cone biopsy with positive margins, and then hysterectomy.
      She is clinically free of disease 15 months after diagnosis. Although the
      diagnosis of malignant schwannoma was suggested by the histologic features of the
      tumors, other diagnoses were entertained and immunohistochemistry was crucial in
      confirming the diagnosis. These tumors should be distinguished from other
      malignant spindle cell tumors of the cervix, such as leiomyosarcoma, endocervical
      "stromal sarcoma," and spindle cell melanoma, so their features, behavior, and
      optimal therapy can be further delineated.

PMID- 9656118
TI  - Leiomyomas of the uterine cervix: a study of frequency.
AB  - Leiomyomas of the cervix are said to be uncommon. To establish their frequency,
      661 consecutive total hysterectomy specimens were examined macroscopically and
      microscopically. Myometrial leiomyomas were present in 427 uteri (64.6%) but
      cervical leiomyoma were present in only 4 (0.6%). One of these was 6 mm in
      diameter and occurred in a uterus without fibroids elsewhere. Only two could have
      been considered clinically significant. An additional six cases showed submucous
      fibroids of the body of the uterus protruding as a polyp into the endocervical
      canal but these were not considered cervical leiomyomas. The conclusion of the
      study is that cervical leiomyomas are extremely uncommon.

PMID- 9656119
TI  - Immunohistochemical analysis of cell cycle regulatory gene products in normal
      trophoblast and placental site trophoblastic tumor.
AB  - Intermediate trophoblast (IT) rarely gives rise to a placental site trophoblastic
      tumor (PSTT) To examine the different growth mechanisms present in normal and
      neoplastic IT, the expression of cell cycle regulatory molecules was compared at
      normal implantation sites and in PSTTs. Normal implantation sites in early
      gestation (19 patients) and PSTTs (6 patients) were immunohistochemically studied
      using antibodies against cytokeratin, human chorionic gonadotropin, and human
      placental lactogen to identify IT, and antibodies against Ki-67, cyclins (A, B,
      D1, and E), cyclin-dependent kinases (cdks), and p53 to investigate the
      proliferative activity of the trophoblast. Marked proliferative activity was
      observed in the trophoblast of the cell columns. Normal IT exhibited a very low
      labeling index for Ki-67, with negative expression for cdks and cyclins, except
      for cyclins B and E. The tumor cells of PSTT exhibited a high labeling index for
      Ki-67 with positive expression for all the cyclins and cdks examined. Expression
      of p53 was identified in tumor cells of PSTTs and the distribution of p53
      positive cells correlated topographically with that of the cyclin A-positive
      cells. The transformed IT of PSTT has high proliferative activity with an
      abnormal expression of cell cycle regulatory molecules, which is not observed in
      normal IT.

PMID- 9656120
TI  - Hepatic (hepatocellular) adenoma of the placenta: a study of four cases.
AB  - Hepatic (hepatocellular) adenoma of the placenta is an extremely rare
      nontrophoblastic placental lesion of disputed histogenesis, four examples of
      which were diagnosed over a 10-year period. The lesions, which were incidental
      findings in women 21 to 30 years of age (mean, 25; median, 24.5), ranged from 0.3
      to 1.0 cm in greatest dimension. Two were found within the villous parenchyma and
      two in subchronic locations. On cross section, two examples were tan to dark red
      nodules without necrosis or hemorrhagic foci, whereas two were not visible
      grossly. The lesions were composed of semidistinct lobules of cords and nests of
      polygonal epithelial cells resembling fetal liver. Extramedullary hematopoiesis
      was a constant feature. The lesional cells contained glycogen and were
      immunoreactive for cytokeratin, alpha-fetoprotein, alpha-1-antitrypsin, and
      carcinoembryonic antigen. Although the histogenesis of these lesions remains
      uncertain, an origin from displaced yolk sac elements with hepatocytic
      differentiation is the most likely hypothesis. It is important to distinguish
      hepatic adenoma of the placenta from placental cell island, heterotopic
      adrenocortical nodule, chorangioma, and placental metastasis of maternal and
      fetal malignancies.

PMID- 9656121
TI  - Primary carcinoma of the fallopian tube: comparative genomic hybridization
      reveals high genetic instability and a specific, recurring pattern of chromosomal
      aberrations.
AB  - Primary fallopian tube carcinoma (PFTC) is a rare and highly aggressive tumor.
      Twelve cases of PFTC (stages IA to IV) were analyzed by comparative genomic
      hybridization. The most consistent DNA gain was mapped to chromosome arm 3q in 11
      of 12 cases. In six cases, the gain of 3q was present as a high level copy number
      increase (amplification) with a consensus region mapped to 3q26.2-qter. In the 12
      cases, other frequent gains were located on chromosome arms 1q (in 11 cases), 2q
      (in 10), 7q (in 9), 8q (in 9), 5p (in 8), 6p (in 7), 12p (in 7), and 14q (in 6).
      Frequent copy number losses occurred on chromosome arms 16q (in 8 cases), 22q
      (in7), 6q (in 6). 8p (in 6), 18q (in 6), Xq (in 6), 1p (in 5), and 17p (in 5).
      All chromosomes were involved in chromosomal aberrations and the average number
      of copy alterations per case was 19.7. None of the 12 carcinomas revealed the
      presence of human papillomavirus (HPV) genomes. All of the cases exhibited crude
      aneuploidy. Strong p53 immunoreactivity could be observed in 10 of 12 cases while
      p21/WAF1 expression was low or undetectable. These results indicate that PFTC is
      a genomically highly unstable cancer, an observation that is in agreement with
      the poor prognosis associated with this tumor. A high frequency of 3q-gains has
      also been observed in HPV-related carcinomas of the uterine cervix. However, none
      of the PFTC was HPV related, suggesting that the 3q-gain is independent from HPV
      DNA.

PMID- 9656122
TI  - Immunohistochemical analysis of bcl-2, bax, mcl-1, and bcl-X expression in
      ovarian surface epithelial tumors.
AB  - Cell survival may be enhanced in tumors by the inhibition of apoptosis, which
      allows tumor promotors to exert their effects. The bcl-2 related genes have been
      shown to contribute to either the inhibition or induction of apoptosis in a
      variety of neoplasms; therefore, it was hypothesized that the expression of these
      genes might contribute to malignant transformation in ovarian surface epithelial
      tumors. The expression of bcl-2 family proteins was investigated in 28 ovarian
      surface epithelial tumors, including serous and mucinous benign, borderline, and
      malignant tumors by immunohistochemical staining with antibodies to bcl-2, bax,
      bcl-X, and mcl-1 proteins. Staining intensity was scored on a 1+ to 3+ scale and
      the benign, borderline, and malignant tumors were compared. Significantly less
      immunoreactive bcl-2 and bcl-X proteins were present in malignant serous tumors
      compared to their benign counterparts. No difference was seen in immunostaining
      for bax or mcl-1 when benign, borderline, or malignant serous tumors were
      compared. In the mucinous tumors, no differences were seen in immunostaining for
      any of the bcl-2 family proteins between tumor types. The loss of expression of
      the antiapoptotic proto-oncogenes bcl-2 or bcl-X in serous carcinomas compared to
      benign serous tumors, together with previous demonstrations that the presence of
      bcl-2 in ovarian surface epithelial cancers is a favorable prognostic indicator,
      suggests that bcl-2 and bcl-X have biological functions in the ovary other than
      inducing apoptosis, acting instead as tumor suppressor proteins.

PMID- 9656123
TI  - Histopathologic and immunohistochemical study of steroidogenic cells in the
      stroma of ovarian tumors.
AB  - The presence of steroidogenic or enzymatically active stromal cells in ovarian
      tumors can lead to various endocrine manifestations by the overproduction of sex
      steroids. We studied the clinicopathologic and immunohistochemical features of
      histologically identified steroid-type cells or enzymatically active cells in the
      stroma of ovarian lesions. Among 1,249 ovarian tumors or tumorlike lesions,
      steroid cells were histologically identified in the stroma in 32 ovarian
      neoplasms, of which 29 were mucinous cystadenomas. The cells were Leydig- or
      hilus-type cells in 4 of the tumors and were lutein-type cells in the remaining
      28. None of the 32 tumors were immuno-reactive for human chorionic gonadotropin
      or luteinizing hormone. Lutein-like steroid cells were intermingled with spindle
      shaped stromal cells and capillaries, while Leydig-type cells were more often
      associated with dilated vessels. The transcription factor of steroidogenesis,
      adrenal 4-binding protein (Ad4BP), was present in nearly all steroid-type stromal
      cells. However, steroidogenic enzymes, 17 alpha-hydroxylase (C17) and 3 beta
      hydroxysteroid dehydrogenase (3 beta SD), were expressed only in 10 of 15 cases
      of histologically identified steroid cells. Steroid cells in which Ad4BP but not
      C17 or 3 beta HSD were expressed were all lutein-type. Aromatase was rarely
      detected in lutein-and Leydig-type cells. The presence of morphologically
      identified steroid cells does not necessarily indicate expression within these
      cells of steroidogenic enzymes, a finding that merits further attention.

PMID- 9656124
TI  - Ovarian endometrioid carcinomas simulating sex cord-stromal tumors: a study using
      inhibin and cytokeratin 7.
AB  - We have investigated the use of inhibin and cytokeratin-7 (CK-7) in
      distinguishing endometrioid ovarian carcinomas (both typical and sex cord-like)
      form granulosa cell and Sertoli cell-containing ovarian tumors.
      Immunohistochemical staining with inhibin, CK-7, and epithelial membrane antigen
      (EMA) was performed on 6 endometrioid carcinomas simulating sex cord-stromal
      tumors, 5 typical endometrioid carcinomas, 14 adult granulosa cell tumors
      (AGCTs), 3 Sertoli-Leydig cell tumors (SCLTs), and 1 sex cord tumor with annular
      tubules (SCTAT). All AGCTs and SLCTs as well as the SCTAT were inhibin-positive.
      In contrast, all of the endometrioid carcinomas (both typical and those mimicking
      sex cord-stromal tumors) were inhibin-negative. CK-7 expression was not observed
      in the granulosa cell tumors and it was noted only in retiform areas in SLCTs.
      All 5 typical endometrioid carcinomas and 5 of the 6 sex cord-like endometrioid
      carcinomas were CK-7 positive. EMA was positive in all carcinomas but negative in
      the SCTAT, AGCTs, and SLCTs. Inhibin can distinguish between sex cord-stromal
      tumors (whether granulosa or Sertoli-Leydig type) and endometrioid carcinomas. CK
      7 is also helpful in differentiating between AGCTs and most endometrioid
      carcinomas, and may also aid in separating SLCTs from sertoliform carcinomas. The
      addition of inhibin to an antibody panel is important because it provides a
      positively-staining marker for sex cord-derived cells.

PMID- 9656125
TI  - Lymphoepitheliomalike carcinoma: an unusual variant of endometrial cancer. A
      report of two cases.
AB  - Two undifferentiated carcinomas of the endometrium with a prominent inflammatory
      reaction that were morphologically similar to nasopharyngeal cancers occurred in
      two patients who had postmenopausal bleeding. Tumor cells in both patients were
      large with indistinct cytoplasmic borders, vesicular nuclei, and prominent
      nucleoli, were arranged in sheets, in groups, or singly, and surrounded by an
      intense inflammatory component of lymphocytes, plasma cells, and karyorrhectic
      debris. Tumor cells were keratin (AE1/EA3) and epithelial membrane antigen (EMA)
      positive and leukocyte common antigen (LCA) negative. All three methods used for
      the detection of Epstein Barr virus (EBV) infection were negative. The first
      patient (International Federation of Gynecology and Obstetrics [FIGO] stage IVB)
      received chemotherapy and is alive and free of disease 9 months after diagnosis.
      The second patient (FIGO stage IIIC) received radiation therapy and chemotherapy
      6 months after evidence of extensive retroperitoneal disease and died of disease
      1 year after diagnosis. Tumors with these histologic features have been
      designated as lymphoepitheliomalike carcinomas (LELC) when they occur outside the
      nasopharynx. LELC can occur in the endometrium and, in this location, may not be
      associated with EBV infection.

PMID- 9656126
TI  - Primary extrarenal Wilms' tumor of the uterus presenting as a cervical polyp.
AB  - Extrarenal Wilms' tumor is rare in any site, and only three cases arising within
      the uterus have been reported. Two of the previous cases were in adolescent
      girls, appearing as polypoid vaginal masses, and the third was in a 22-year-old
      woman who had menometrorrhagia. An extrarenal Wilms' tumor in an 11-year-old girl
      that initially appeared as a 10-cm polyp protruding through the cervix is
      described. Triphasic differentiation with mesenchymal stroma showing
      rhabdomyoblastic differentiation both morphologically and immunohistochemically
      was demonstrated. Epithelial differentiation with focal glomerular
      differentiation also was present. Most of the primary tumor and almost the entire
      recurrent tumor were composed of blastemal cells. The diagnosis of an extrarenal
      Wilms' tumor should be entertained when examining a polypoid tumor of the cervix
      or a polypoid mass within the vagina in an adolescent patient.

PMID- 9656127
TI  - Recurrent mixed germ cell-sex cord-stromal tumor of the ovary in an adult.
AB  - A 32-year-old woman underwent laparotomy and right salpingo-oophorectomy for a
      right adnexal mass. Examination of the specimen revealed a 77 g well-encapsulated
      tumor that was diagnosed as a mixed germ cell-sex cord-stromal tumor with annular
      tubules. Sixty-seven months after an uneventful recovery, a large recurrence was
      treated by total abdominal hysterectomy, left salpingo-oophorectomy, removal of
      peritoneal implants, lymphadenectomy, omentectomy, and chemotherapy.
      Histologically, the neoplasm was identical to the one found in the right ovary.
      To our knowledge, no similar case has been previously reported.

PMID- 9656128
TI  - Bilateral atypical hyperplasia of the fallopian tube associated with tamoxifen: a
      report of two cases.

PMID- 9656129
TI  - Error-correction problems in autism: evidence for a monitoring impairment?
AB  - With a task involving the launching of missiles at targets, Malenka et al. (1982)
      and C. Frith and Done (1989) showed that schizophrenic patients with delusions of
      alien control and auditory hallucinations were likely to leave erroneous
      responses uncorrected whose outcomes were not visible until the missile hit or
      failed to hit the target, while being able to correct visible errors adequately.
      This is consistent with an impairment in the central monitoring of action. Using
      a similar task, we found that children with autism were more likely than controls
      to fail to correct both kinds of error. Data are interpreted in terms of
      difficulties with constructing visual schemata for actions.

PMID- 9656130
TI  - Using objects of obsession as token reinforcers for children with autism.
AB  - We assessed the effectiveness of using objects of obsession as token reinforcers
      to increase task performance for children with autism. The use of obsessions as
      tokens (e.g., letter "A", a picture of a train) was compared with the use of
      typical tokens (e.g., stars, happy faces). A multiple baseline design across
      children with a reversal within child was used. Data were collected on percentage
      correct of task responses and on the occurrence of inappropriate behaviors during
      work sessions. Results indicated that percentage correct on task performance was
      higher when objects of obsession were used as tokens as opposed to when typical
      tokens were used. Concomitant decreases in inappropriate behaviors during work
      sessions were also noted. Results are discussed in terms of primary versus
      secondary reinforcement and the effects of saliency and novelty of the
      reinforcing stimuli.

PMID- 9656132
TI  - Sex as a possible source of group inequivalence in Lovaas (1987)
AB  - The possibility of differential sex proportions as a confounding factor in the
      Lovaas (1987) study is raised in this paper. It is argued that the chi-square
      analysis reported in the original study was inadequate and that the appropriate
      comparison should be made not between the experimental group and primary control
      group (Control Group 1) utilizing expected cell frequencies estimated from sample
      data, but between these two groups using population data to estimate expected
      cell frequencies. Implications of this interpretation are discussed.

PMID- 9656131
TI  - Timing of social gaze behavior in children with a pervasive developmental
      disorder.
AB  - The aim of the study was to compare social initiatives and gaze behavior in low
      functioning children with a pervasive developmental disorder (PDD), high
      functioning children with a PDD, children with a language disorder, and normally
      developing children. Behavior of the children was observed while they watched
      television and performed a playful task with a parent. Compared to the high
      functioning children, the low-functioning children with a PDD showed fewer social
      initiatives. The high-functioning children with a PDD did not differ from the non
      PDD control children in the number of social initiatives and gazes. However, in
      children with PDD, timing of social gaze proved to be different in that they had
      lower levels of visual checking before but not after a declarative pointing
      gesture. Furthermore, they had lower levels of returning gaze.

PMID- 9656133
TI  - Autism and related disorders: epidemiological findings in a Norwegian study using
      ICD-10 diagnostic criteria.
AB  - Recent studies of the prevalence of autism have suggested higher estimates than
      previously described. Various diagnostic criteria for autism and related
      disorders have been applied, with variability in case finding methodology and
      characteristics of populations as well. In this study, maternal and child health
      clinics covering 98% of the population were used for screening pervasive
      developmental disorders. Extensive medical investigation was carried out on the
      majority of cases. In this Norwegian population of children ages 3-14 years the
      minimum prevalence estimate for childhood autism was 4-5 per 10,000 using ICD-10
      research criteria, and did not confirm the high estimates suggested more
      recently. Medical disorders identified were associated with mental retardation
      rather than specifically with autism.

PMID- 9656134
TI  - Risperidone for aggression and self-injurious behavior in adults with mental
      retardation.
AB  - Risperidone has proven efficacy with reduced likelihood of causing extrapyramidal
      symptoms in the treatment of schizophrenia. Initial work suggests its utility in
      the management of aggression and self injury in patients with mental retardation.
      The use of risperidone in eight adult patients with moderate to profound mental
      retardation is described. Risperidone in these individuals was associated with
      significant reduction in aggression and self injurious behavior. Side effects
      were primarily those of sedation and restlessness. These cases illustrate the
      possible utility of risperidone in the treatment of aggression and self injury in
      adult patients with moderate to profound mental retardation.

PMID- 9656135
TI  - Diabetes insipidus and polydipsia in a patient with Asperger's disorder and an
      empty sella: a case report.
AB  - The paper describes a patient with Asperger disorder, Neurogenic Diabetes
      Insipidus (NDI) and Primary Empty Sella (ES). His response to vasopressin
      treatment suggested a concomitant presence of primary polydipsia. This is the
      first reported case of an autistic spectrum disorder associated with NDI or ES.
      The implications of the observed co-occurrence of these relatively rare disorders
      are discussed in relation to diagnosis and pathogenesis.

PMID- 9656136
TI  - Increasing speech intelligibility in children with autism.
AB  - Accumulating studies are documenting specific motivational variables that, when
      combined into a naturalistic teaching paradigm, reliably influence the
      effectiveness of language teaching interactions for children with autism.
      However, the effectiveness of this approach has not yet been assessed with
      respect to improving speech intelligibility. The purpose of this study was to
      systematically compare two intervention conditions, a Naturalistic approach
      (which incorporated motivational variables) vs. an Analog (more traditional,
      structured) approach, with developmentally similar speech sounds equated within
      and across conditions for each child. Data indicate that although both methods
      effectively increased correct production of the target sounds under some
      conditions, functional use of the target sounds in conversation occurred only
      when the naturalistic procedures were used during intervention. Results are
      discussed in terms of pivotal variables that may produce improvements in speech
      sounds during conversational speech.

PMID- 9656137
TI  - Brief report: a case of chromosome 22 alteration associated with autistic
      syndrome.
AB  - The author described a male patient, age 13 years and 5 months, with behavioral
      profile meeting the criteria of the autistic syndrome by the DSM-III-R (APA,
      1989) and DSM-IV (APA, 1995). After clinical and laboratory examinations, it was
      found that he had an abnormal karyotype, 46 XY, R(22). The need for clinical and
      laboratory case studies of autism is of great importance to develop data for
      defining an etiological basis for diagnosis.

PMID- 9656139
TI  - Is auditory integration training safe?

PMID- 9656138
TI  - Brief report: interpretation of facial expressions, postures and gestures in
      children with a pervasive developmental disorder not otherwise specified.

PMID- 9656140
TI  - Recently diagnosed with autism, autism or not.

PMID- 9656141
TI  - Protective effect of ciliary neurotrophic factor (CNTF) in a model of endotoxic
      shock: action mechanisms and role of CNTF receptor alpha.
AB  - Ciliary neurotrophic factor (CNTF) inhibits the production of tumor necrosis
      factor (TNF) in lipopolysaccharide (LPS)-treated mice and protects against LPS
      lethality when coadministered with its soluble receptor (sCNTFR alpha). Both of
      these activities are abolished in adrenalectomized (ADX) mice. LPS-induced
      pulmonary polymorphonuclear neutrophil (PMN) infiltration and nitric oxide (NO)
      production were also inhibited by CNTF + sCNTFR alpha but not by CNTF alone.
      sCNTFR alpha did not alter the clearance or tissue distribution of CNTF.
      Furthermore, CNTF variants coadministered with sCNTFR alpha protected against LPS
      toxicity in a manner related to their affinity for the beta components of CNTFR.
      Thus, inhibition of TNF production and protection against LPS lethality by
      CNTF/sCNTFR alpha require an intact hypothalamus-pituitary-adrenal axis (HPAA)
      and may be mediated by endogenous glucocorticoids. This protective effect is, at
      least in part, due to the inhibition of PMN infiltration and NO production, and
      appears to be mediated by cells displaying only beta-receptor subtypes.

PMID- 9656142
TI  - Distinct inflammatory responses of adherent vascular lung neutrophils to
      pulmonary irritants.
AB  - The nature and the extent of the damage that occurs in the lung following
      exposure to pulmonary irritants vary with the pathogenic agent. In the present
      studies we determined if this was due to unique functional responses of adherent
      vascular neutrophils to different irritants. Because of their location within the
      lung, these cells may be more relevant than circulating neutrophils to the
      pathophysiology of irritant-induced lung injury. For our studies we used two
      model irritants, ozone and endotoxin, which cause distinct pathologic effects in
      the lung. Treatment of rats with ozone resulted in a transient increase (2-fold)
      in the number of adherent vascular neutrophils in the lung which was maximum 2 hr
      after exposure and returned to control levels by 12 hr. In contrast, following
      endotoxin administration, 10-fold greater numbers of adherent neutrophils were
      recovered from the lung. Moreover, cell number remained elevated 3-fold for up to
      48 hr. Unstimulated neutrophils isolated 2-12 hr after endotoxin treatment of
      rats produced 3 times more superoxide anion than cells from ozone-treated rats.
      Cells isolated 12-48 hr after endotoxin administration were also sensitized to
      produce more nitric oxide than cells from ozone-treated rats and to express
      inducible nitric oxide synthase protein. These data demonstrate that endotoxin
      and ozone induce distinct patterns of accumulation and functional changes in
      adherent vascular neutrophils in the lung which may contribute to different
      pathological processes observed following exposure to these pulmonary irritants.

PMID- 9656143
TI  - Involvement of Ets, rel and Sp1-like proteins in lipopolysaccharide-mediated
      activation of the HIV-1 LTR in macrophages.
AB  - The HIV-1 promoter was used as a model to identify transcription factors involved
      in LPS-dependent transcription in RAW 264 murine macrophages. Expression plasmids
      for Ets-2 and PU.1 trans-activated the HIV-1 LTR and recombinant PU.1 and an Ets
      2 DNA binding domain/GST fusion protein bound to the 5' kappa B site of the HIV-1
      enhancer. Ets-2 mRNA was LPS-inducible in RAW 264 cells and LPS stimulated
      phosphorylation of threonine 72 residue within the Ets-2 pointed domain.
      Induction of Ets-2 and other LPS-responsive transcription factors was also
      observed upon addition of plasmid DNA, which complicates interpretation of
      transient transfections. The proximal promoter region, containing two Sp1 sites,
      was also LPS-responsive. We propose that the kappa B elements and the tandem Sp1
      sites act as LPS response elements and that kappa B-mediated LPS action involves
      Ets and rel factors.

PMID- 9656144
TI  - Zero-crossing derivative spectrophotometry for the determination of haloperidol
      in presence of parabens.
AB  - First derivative spectrophotometry with a zero-crossing technique of measurement
      is used for the quantitative determination of haloperidol in the presence of
      methylparaben and propylparaben, which is added as antimicrobial preservatives in
      pharmaceuticals. This technique permits the quantification of haloperidol in the
      presence of parabens, with closely overlapping spectral bands, and without any
      separation step. Linear calibration graphs of first derivative values (at 255.2
      nm for haloperidol) versus concentration (in the range 4.0-20.0 micrograms ml-1)
      were obtained with negligible intercepts. Relative standard deviation of 0.83%
      was obtained for intra-day precision and 1.86% for inter-day precision. The
      recovery of haloperidol in synthetic mixtures with parabens and pharmaceutical
      dosage forms is also reported.

PMID- 9656145
TI  - Assay of effervescent tablets by near-infrared spectroscopy in transmittance and
      reflectance mode: acetylsalicylic acid in mono and combination formulations.
AB  - Near-infrared spectroscopy (NIRS) was used to determine acetylsalicylic acid
      (ASA) in three different effervescent tablet formulations. The nominal ASA
      concentrations were 14.9% in the single substance formulation (ASA Mono), 17.4%
      in the combination with ascorbic acid (ASA + C) and 8.7% in the combination with
      paracetamol and ascorbic acid (ASA Combi). In each case the tablet matrix was
      composed of seven excipients typical of effervescent tablets. All three
      formulations were measured as intact tablets in diffuse transmittance and
      reflectance and as powdered tablets in diffuse reflectance. Calibration was
      carried out by partial least square (PLS) regression of second derivative
      spectra. High-performance liquid chromatography (HPLC) was used as the reference
      method. The relative standard errors of calibration (RSEC) achieved for the three
      NIR methods were between 1.20 and 2.01% for ASA Mono, between 1.91 and 2.21% for
      ASA + C and between 2.41 and 4.50% for ASA Combi. The results obtained in
      transmittance mode were comparable with those obtained in reflectance mode, which
      is normally used in NIRS. In the test sets of ASA Mono and ASA + C relative root
      mean square (RRMS) values between 2.21 and 3.13% were obtained. The three NIR
      methods applied are thus suitable for the quantitative determination of ASA in
      effervescent tablets and have the advantage over HPLC of being rapid and simply
      carried out with little sample preparation; they are nondestructive and do not
      require any environmentally harmful reagents.

PMID- 9656146
TI  - Determination of relative acidities of some alpha, omega-bis(3-alkyl(aryl)-4,5
      dihydro-1H-1,2,4-triazol-5-on-4-yl) alkanes.
AB  - The solutions of nine alpha, omega-bis(3-alkyl(aryl)-4,5-dihydro-1H-1,2,4-triazol
      5-on-4-yl) alkanes were titrated with tetrabutylammoniumhydroxide (TBAH) in
      methanol, using potentiometric methods. The half neutralization potentials values
      were found for all cases. Potentiometric titration curves of compounds in
      methanol with 0.03 M TBAH are similar to those of weak acids obtained in aqueous
      media with strong bases. Methanol is found to be a suitable medium for the weakly
      acidic compounds titrated since they are poorly dissolved in other organic
      solvents. A comparison among the compounds having the same alkyl chains between
      the two ring systems has shown that basicity increases and acidity decreases as
      the size of alkyl chains increases. However, the compound with a substituted
      phenyl group was found to be the most acidic one among the examined compounds
      indicating that phenyl group donates ring electrons less effectively to the
      system. This can be attributed to the stability of the benzene ring.

PMID- 9656147
TI  - Simultaneous determination of melatonin-pyridoxine combination in tablets by zero
      crossing derivative spectrophotometry and spectrofluorimetry.
AB  - Two methods have been developed for the analysis of melatonin (M) and pyridoxine
      hydrochloride (PH) in combination. The first method depends on first- and second
      derivative ultraviolet spectrophotometry, with the zero crossing technique of
      measurement. First-derivative amplitudes at 296 nm and second-derivative
      amplitudes at 294 and 322 nm are selected for the determination of M and PH,
      respectively. The second method is based on the native fluorescence of both M and
      PH, in methanol and 0.1 M hydrochloric acid, respectively, after a preliminary
      solvent extraction procedure. The relative standard deviation of both methods was
      less than 2.0%. The two methods have been successfully applied to the
      determination of both drugs in laboratory-prepared mixtures and in tablets.

PMID- 9656148
TI  - Separation and determination of sorbitol and xylitol in multi-component
      pharmaceutical formulations by capillary isotachophoresis.
AB  - Pharmaceutically important polyhydric alcohols sorbitol (SO) and xylitol (XY) are
      efficiently separated and determined by analytical capillary isotachophoresis
      (ITP) with conductometric detection. The on-column complex-formation equilibria
      between the polyols and boric acid are utilized--the terminating borate ion acts
      as the complexing agent. The ITP operational system used consists of 10 mM HCl +
      20 mM imidazole (LE, pH 7.0) and 20 mM boric acid (TE, pH 8.0). The effective
      mobilities of the borated SO and XY are 8.3 x 10(-9) m2 V-1 s-1 and 7.4 x 10(-9)
      m2 V-1 s-1, respectively. The ITP analysis is performed with the driving and
      detection currents of 50 microA (for 700 s) and 20 microA, respectively. The
      calibration graphs are rectilinear in the range 25-250 mg l-1 of SO and 50 to 500
      mg l-1 of XY. The method is applied to the simultaneous assay of SO and XY in
      three mass-produced multi-component infusion solutions. Favourable values of the
      method validation parameters obtained confirm the suitability of the proposed ITP
      method for the quality control of pharmaceuticals.

PMID- 9656149
TI  - GC-MS analysis of incenses for possible presence of allergenic nitromusks.
AB  - A Gas chromatographic method with mass detector was developed to identify and
      determine nitromusks in incense sticks of different origin (India, China, Tibet).
      The proposed method was found useful to correlate dermatological allergic
      reactions with the use and composition of commercial incense sticks. The incense
      sticks were powdered, extracted with methanol and after the addition of 1
      eicosanol as internal standard, injected into the GC-MS, using 25 m bonded phase
      fused capillary column methyl, 5% phenyl silicone (0.32 mm I.D., 0.25 microns
      film thickness). Musk ambrette was identified and determined in one kind of
      chinese incense together with musk ketone and musk xylene. The latter compound
      was also found alone in another kind of chinese incense.

PMID- 9656150
TI  - Validation of a liquid chromatographic tandem mass spectrometric method for the
      determination of sumatriptan in human biological fluids.
AB  - A liquid chromatographic tandem mass spectrometric method for the quantitative
      determination of sumatriptan base in human plasma and urine has been developed
      and validated over the concentration range 0.2-20 ng base ml-1. Sumatriptan is a
      5-HT1 receptor agonist which has found widespread use in the treatment of
      migraine. Sumatriptan and its internal standard (D3-sumatriptan) were extracted
      from human matrices using C2 solid phase cartridges. The extracts were
      chromatographed on a C18 column, ionised using a heated nebuliser assisted
      atmospheric pressure ionisation (API) interface and detected by MS/MS in the
      multiple reaction monitoring mode. The completed validation demonstrated the
      method to be robust, accurate, precise and specific for the direct quantification
      of sumatriptan in human fluids. The method was used on a routine basis to
      determine the levels of sumatriptan in human volunteers following the oral
      administration of a 25 mg dose of sumatriptan succinate.

PMID- 9656151
TI  - The control over the new obtaining procedeum of indomethacin.
AB  - The synthesis of the indomethacin (1H-indole-3-acetic acid, 1(4-chlorobenzoyl)-5
      methoxy-2-methyl) was achieved through a new method, which reduces some stages
      from the previous methods. Both the structure of the finished product and the
      structures of the intermediaries were investigated by chromatographic methods
      (TLC, chromatography on column, GC-MSD) and spectroscopic methods (UV, IR, 1H
      NMR, 13C-NMR). The chromatographic and spectroscopic studies proved that these
      had a special analytical value and they serve to control synthesis and to
      identify the compounds in all the stages of the process.

PMID- 9656152
TI  - Stability of adenosine in infusion.
AB  - Using liquid chromatography the stability of adenosine in aqueous solution was
      investigated at five different temperatures, namely 4, 22, 37, 60 and 72 degrees
      C over a period of 6 months. At the three lowest temperatures, the initial
      concentration of the product was not altered, at the highest temperatures there
      was a significant decrease. From these data the shelf life (t90) at room
      temperature was estimated to be at least 5 years.

PMID- 9656153
TI  - Reproducibility of 1H-NMR integrals: a collaborative study.
AB  - The quantitative use of NMR spectroscopy was investigated by a reproducibility
      study of 1H-NMR integrals involving five laboratories. A significant laboratory
      effect was found confirming the difficulty to obtain very precise data by
      integration of complex signals. The reproducibility of any NMR assay measurement,
      which requires a high precision should be validated by an interlaboratory study.

PMID- 9656154
TI  - Determination of bisnafide, a novel bis-naphthalimide anticancer agent, in human
      plasma by high-performance liquid chromatography with UV detection.
AB  - A simple, specific, and sensitive high-performance liquid chromatographic (HPLC)
      assay utilizing ultraviolet (UV) detection for the determination of bisnafide in
      human plasma was developed, validated, and applied to plasma samples from
      patients undergoing cancer therapy. Plasma samples, containing an internal
      standard, XE842, were first deproteinized with 2.0 ml acetonitrile, and
      subsequently, 1.0 ml and pH 9 boric acid-potassium chloride-sodium hydroxide
      buffer (0.1 M) was added. To this mixture, 9.0 ml of ethyl ether was added then
      vortex mixed. Following centrifugation, the ether layer was back-extracted into
      250 microliters of 0.1 M phosphoric acid, then removed by vacuum aspiration. A
      portion of the remaining acid layer was directly injected onto the HPLC.
      Bisnafide was quantified using a Shiseido Capcell Pak C8 HPLC column and
      ultraviolet detection (274 nm). The lower limit of quantification was 10 ng ml-1
      using 1.0 ml plasma. The intraday precision (RSD) ranged from 2.7 to 8.6% over a
      concentration range of 10-1000 ng ml-1. The interday precision (RSD) ranged from
      5.6 to 11.5%. Overall mean accuracy was +/- 5.2%. The drug was stable in frozen
      heparinized human plasma stored at -20 degrees C for at least 1 year and stable
      throughout at least two freeze-thaw cycles. This method was successfully utilized
      for quantifying plasma concentrations needed to study the clinical
      pharmacokinetics of bisnafide in patients undergoing cancer therapy.

PMID- 9656155
TI  - Spectrophotometric and high performance liquid chromatographic determination of
      cetirizine dihydrochloride in pharmaceutical tablets.
AB  - Derivative spectrophotometric, colorimetric and high performance liquid
      chromatographic methods, for the determination of the antihistaminic cetirizine
      dihydrochloride in tablet form were described. Spectrophotometrically, cetirizine
      was determined by the measurement of its first (1D) and second (2D) derivative
      amplitudes at 239 (peak) and 243-233 nm (peak-to-trough), respectively. The
      aqueous solutions obeyed Beer's law in the concentration ranges of 1.2-10.0 and
      0.8-10.0 micrograms ml-1 for 1D and 2D measurements, respectively. The
      colorimetric procedure was based on measuring the absorbency of the coloured
      chromogen resulted from the reaction between cetirizine sodium salt in polar
      solvent (DMF) and chloranil at 556 nm. The relation with concentrations was
      linear over 120-250 micrograms ml-1. Optimization of the reaction conditions was
      studied. At the same time, investigation of the complex formed was made with
      respect to its composition and the associated constant. A simple liquid
      chromatographic assay has been developed for the determination of cetirizine
      dihydrochloride in the presence of one of its synthesis precursor (hydroxyzine
      hydrochloride). A Bondapak-C18 column was used with a mobile phase consisting of
      acetonitrile/0.01 M ammonium dihydrogen phosphate (32:68, v/v) containing 0.1%
      w/v tetrabutyl ammonium hydrogen sulphate adjusted to pH 3 with phosphoric acid
      at a flow rate of 2 ml min-1. With salicylic acid as internal standard,
      quantitation was achieved with UV detection at 230 nm based on the peak height
      ratios. Beer's law was obeyed in a concentration range of 3-35 micrograms ml-1
      and the regression line equation was derived with a correlation coefficient of
      0.9999. The validity of the methods was further confirmed using the standard
      addition method. The proposed procedures were successfully applied to the
      determination of cetirizine in bulk and tablet form, with high percentage of
      recovery, good accuracy and precision.

PMID- 9656156
TI  - An approach to the evaluation and comparison of reversed-phase high-performance
      liquid chromatography stationary phases.
AB  - An approach to the evaluation and comparison of reversed-phase high-performance
      liquid chromatography stationary phases with particular emphasis on data analysis
      and presentation is described. Assessment is based on the peak efficiency,
      asymmetry (USP tailing factor) and relative retention properties shown by 24
      basic compounds having a wide range of structural and physico-chemical
      properties. A novel approach to data normalisation and presentation is described.
      This overcomes the problems associated with the quality of the column packing
      process, as well as differences in stationary phase selectivity which in
      conjunction with extra column band broadening effects can make comparisons
      meaningless.

PMID- 9656157
TI  - Comparison of LC detection methods in the investigation of non-UV detectable
      organic impurities in a drug substance.
AB  - HPLC Analysis with different detection methods was shown to be essential in the
      separation and identification of unknown organic impurities in a drug substance.
      The impurities were found to exhibit very weak or no response to standard
      ultraviolet (UV) absorption detection. LC-MS, LC-NMR, indirect, refractive index
      and evaporative light-scattering detection were used to quantify and identify the
      impurities in this specific case. The drug substance studied was found to be an
      ideal analyte for demonstrating the advantages and limitations of several
      chromatographic detection systems for impurity profile analysis.

PMID- 9656158
TI  - The use of near-infrared spectroscopy in the efficient prediction of a
      specification for the residual moisture content of a freeze-dried product.
AB  - The purpose of this study is to improve the efficiency in the search for a
      suitable specification for the residual moisture content in a freeze-dried
      product. A near-infrared spectroscopic (NIRS) method was developed for the
      measurement of the residual moisture content. Samples with a wide range of
      residual moisture contents were stored for two months at 8, 50, and 60 degrees C.
      Because of the non-destructive character of the NIRS method initially the
      residual moisture content and, subsequently, the content of the active ingredient
      could be measured in the same sample vials after storage. Plots of the residual
      moisture content against the content of the active ingredient were made for
      storage at 50 and 60 degrees C. For this only 69 samples were needed in the
      stability study for the assay determination while traditionally a five-fold of
      samples is needed because of the high intra-batch variability of the residual
      moisture content. The plots at 50 and 60 degrees C were combined with the
      Arrhenius relationship between degradation rate constant and temperature. The
      maximal allowable residual moisture content was calculated with product shelf
      lives of 2 and 3 years and storage temperatures of 20, 25, and 30 degrees C,
      respectively.

PMID- 9656159
TI  - Quantitation of amphotericin B in plasma by second-derivative spectrophotometry.
AB  - A method is described for determining amphotericin B in plasma using second
      derivative spectrophotometry after deproteinization. The assay was based on the
      absorbance at 407.5 nm. The second-derivative spectrum recorded between 350 and
      450 nm allowed identification of the analyte and showed absence of drug
      interference. Only bilirubin interfered at high concentration (> or = 50 mumol l
      1. The linear concentration ranges were 0.05 -5.0 mg l-1 (r = 0.999, slope =
      2.731, intercept = 0.008). Between-day CV < or = 9.7%, within-day CV < or = 5.5%,
      analytical recovery close to 100% were suitable for clinical investigations. This
      method provides better specificity than direct absorbance, is simpler and faster
      than a high performance liquid chromatography assay and can be used routinely by
      any laboratory possessing a spectrophotometer with a derivative accessory.

PMID- 9656160
TI  - Determination of 2-hydroxyphenylacetic acid (2HPAA) in urine after oral and
      parenteral administration of coumarin by gas-liquid chromatography with flame
      ionization detection.
AB  - The urinary excretion of 2-hydroxyphenylacetic acid (2HPAA) was studied in human
      volunteers after oral and parenteral doses of coumarin. The presence of 2HPAA in
      the urine was confirmed by gas chromatography mass spectroscopy (GC MS). Mass
      spectra of reference material and samples are presented. The determination of
      2HPAA was carried out by GC with flame-ionization detection. Prior to analysis
      samples were extracted into ethyl ether and the analytes were derivatized with
      trimethlyphenylammonium hydroxide. A calibration range from 0.3 to 150 micrograms
      ml-1 was established using 3-hydroxyphenyl acetic acid (3HPAA) as an internal
      standard. On average less than 10% of the coumarin administered were excreted
      into the urine in the form of 2HPAA.

PMID- 9656161
TI  - Evaluation of a novel diffusion cell for in vitro transdermal permeation: effects
      of injection height, volume and temperature.
AB  - The objective of this study was to evaluate the performance of a new, compact,
      dynamic diffusion cell for in vitro transdermal permeation. These so-called
      Kelder-cells were developed as an automated alternative to the static Franz
      diffusion cells. The new cells were used in combination with the ASPEC-system
      (automatic sample preparation with extraction columns) which was initially
      designed for the automation of solid-phase extractions. Three variables were
      tested to optimize the performance of the new cell system: injection height into
      the inlet compartment, volume flowing through the receptor compartment and
      temperature. Experiments were performed using the tritium labelled
      anticholinergic [3H]dexetimide permeating through an artificial membrane
      (Silastic). The injection height of the needle into the inlet compartment of the
      cell should be programmed at -34 mm to ensure complete air tightness, thus
      forcing the buffer to flow through the cell. The volume of buffer flow through
      the receptor compartment is important in maintaining sink conditions: a volume of
      117 microliters was chosen to replace the total content of the cell (84
      microliters) every 2 min. The temperature was precisely controlled in a
      thermostatic cabinet to minimize variations in experimental conditions. For
      [3H]dexetimide, an increase in temperature of 20 degrees C reduced the lag time
      by a factor of approximately two, however the influence on the flux was
      negligible. The data for the Kelder-cells were comparable with static Franz
      diffusion cells at a pseudo-steady state, however Kelder-cells have the advantage
      of automatic sampling, continuous replacement of the receptor solution, and
      unattended operation over at least 24 h.

PMID- 9656162
TI  - Spectrophotometric method for the determination of paracetamol and phenacetin.
AB  - A rapid, sensitive and simple spectrophotometric method is proposed for the
      determination of hydrolysis products of paracetamol (PRL) and phenacetin (PHN)
      with sodium 1,2-naphthoquinone-4-sulphonate and cetyltrimethyl ammonium bromide
      (CTA) in alkaline medium. The absorbances are measured at 570 and 500 nm and the
      molar absorptivities found to be 1.118 x 10(4) and 4.54 x 10(3) l mol-1 cm-1 for
      PRL and PHN, respectively. The coloured species conforms to Beer's law over the
      range 1-20 micrograms ml-1 for PRL and 2-24 micrograms ml-1 of PHN. The
      sensitivity is enhanced by the addition of CTA. The method is successfully
      employed for determination of PRL or PHN in various pharmaceutical preparations
      and laboratory made tablets and results have been statistically compared with
      those obtained by the official method.

PMID- 9656163
TI  - Error structure for the HPLC analysis for atenolol, metoprolol and propranolol: a
      useful weighting method in parameter estimation.
AB  - Three reversed-phase high performance liquid chromatography (HPLC) methods with
      UV detection were developed and fully validated for the quantification of three
      beta-blockers: atenolol, metoprolol and propranolol. After validation, error
      structures for the HPLC analysis were established using a convenient and
      practical procedure. The mean percentage of relative standard deviation (RSD) of
      the experimental concentrations (C), were less than 4.29% for proportionality and
      less than 3.68% for precision for any of the drugs, which allowed the
      quantitation of beta-blockers assayed at concentrations in the range 25-0.78
      micrograms.ml-1. The error structures for the HPLC analysis were: SD
      (micrograms.ml-1) = 5.02 x 10(-2) C for atenolol, SD (micrograms.ml-1) = 4.55 x
      10(-2) + 0.63 x 10(-2) C - 7.58 x 10(-6) C3 for metoprolol and SD (micrograms.ml
      1) = 2.73 x 10(-2) C - 3.49 x 10(-4) C2 for propranolol. The reciprocal of the
      square of the SD of the drug concentrations measured within the calibration curve
      could be used as weighting methods in parameter estimation by non-linear
      regression.

PMID- 9656164
TI  - Determination of piroxicam and its major metabolite 5-hydroxypiroxicam in human
      plasma by zero-crossing first-derivative spectrophotometry.
AB  - A zero-crossing first-derivative spectrophotometric method for the determination
      of piroxicam and its major metabolite 5-hydroxypiroxicam (5-HP) in human plasma
      is described. This technique permits the quantification of compounds with closely
      overlapping spectral bands without any separation step. The method consists of
      direct extraction of the less-ionised forms of piroxicam and 5-hydroxypiroxicam
      with pure diethyl ether. First derivative values at 343.5 and 332.5 nm for
      piroxicam and 5-HP, respectively, were obtained. The absolute recovery of the
      method was found to be 89.4% for piroxicam and 90.3% for 5-HP. Calibration graphs
      are linear (r better than 0.9998), with zero-intercept, in the concentration
      range 0.5-12.0 micrograms ml-1 for both compounds. The limits of quantification
      attained according to the IUPAC definition were 0.29 and 0.27 micrograms ml-1 for
      piroxicam and 5-HP, respectively. The results obtained by the proposed method
      were in good agreement with those found by the high-performance liquid
      chromatographic method (HPLC).

PMID- 9656165
TI  - A rapid liquid chromatographic method for the determination of lamotrigine in
      plasma.
AB  - A rapid sensitive and simple high-performance liquid chromatographic (HPLC)
      method for the determination of lamotrigine in plasma is described. The drug was
      extracted from 100 microliters of plasma with chloroform:isopropanol (95:5% v/v)
      in the presence of 100 microliters of phosphate buffer (10 mM). The extract was
      evaporated and the residue was reconstituted with mobile phase and injected onto
      the HPLC system. The drug and the internal standard (chloramphenicol) were eluted
      from a Symmetry C18 stainless steel column at ambient temperature with a mobile
      phase consisting of 0.01 M potassium-acetonitrile-methanol (70.20:10% v/v/v),
      adjusted to pH 6.7, at a flow rate of 1.3 ml min-1 and the detector was monitored
      at 214 nm. Quantitation was achieved by measurement of the peak-area ratio of the
      drug to the internal standard and the lower limit of detection for lamotrigine in
      plasma was 20 ng ml-1. The intraday precision ranged from 3.34 to 6.12%
      coefficient of variation (CV) and the interday precision ranged from 2.15 to
      8.34% CV. The absolute and relative recoveries of lamotrigine ranged from 86.93
      to 90.71% and from 95.18 to 107.13%, respectively. The method was applied in
      studying the pharmacokinetics of lamotrigine administered orally to rabbits. This
      reliable micro-method would have application in pharmacokinetic studies of
      lamotrigine where only small sample sizes are available, e.g. paediatric
      patients.

PMID- 9656166
TI  - Liquid chromatographic determination of a non-steroidal oral contraceptive CDRI
      85/287 in rat serum.
AB  - A precise and sensitive high performance liquid chromatographic (HPLC) assay
      method was developed and validated for the quantitation of 2-[4-(2
      piperidinoethoxy) phenyl]-3-phenyl-(2H)-1-benzo(b)pyran (compound CDRI-85/287) in
      rat serum. This method, applicable to 0.5 ml volumes of serum, was validated
      according to GLP guidelines. It involved double extraction of serum samples with
      a mixture of hexane and iso-propanol (98:2 v/v) at alkaline pH and the use of UV
      detection at 332 nm. Linearity, precision and accuracy were acceptable (5-200 ng
      ml-1. The absolute recovery was more than 75% and the lower limit of quantitation
      was 5 ng ml-1. Freeze-thaw stability studies up to four cycles showed no apparent
      differences in the calculated spiked concentrations. However, in-process
      stability evaluation showed the stability of the processed samples lasted up to
      85 h.

PMID- 9656167
TI  - Separation and estimation of seven vasodilators using packed column supercritical
      fluid chromatography.
AB  - This paper reports a method for an isocratic separation and simultaneous
      estimation of seven vasodilators: isosorbide mononitrate (ISMN), isosorbide
      dinitrate (ISDN), cyclandelate, nimodipine, amlodipine, pentifylline and
      pentoxifylline using packed column supercritical fluid chromatography (SFC). An
      arbitrary choice of vasodilatory compounds with respect to their chemical
      structures was made to examine the viability of this technique for analysis of
      drugs and pharmaceuticals. Elution was performed on a RP-C18 column. SFC offers
      several degrees of freedom: temperature, pressure and modifier concentration to
      attain optimum resolution and sensitivity. The effects of these parameters on
      retention time have been studied using methanol modified carbon dioxide. The
      analytes were identified and measured by UV-detection. The chromatographic points
      of merit have been listed. Detection limits appear to be similar to those found
      in liquid chromatography. Modifier concentration does generally make major
      changes in retention and selectivity. A full scale validation for the seven
      vasodilators has been attempted and the statistical quality evaluated.

PMID- 9656168
TI  - Simultaneous detection of cisatracurium, its degradation products and propofol
      using positive ion detection followed by negative ion detection in a single LC/MS
      run.

PMID- 9656169
TI  - Palatal augmentation prosthesis with alternative palatal vaults for speech and
      swallowing: a clinical report.

PMID- 9656170
TI  - A two-stage resin-bonded fixed partial denture seated in conjunction with
      postextraction healing of the alveolar socket: a clinical report.
AB  - A patient treatment modality that involved a two-stage resin-bonded FPD was
      presented in this clinical report. During recovery of the alveolar socket, a
      direct bonded acrylic pontic was seated with an adhesive resin (Super-Bond C&B
      Clear). This primary prosthesis provided service for 6 months without trouble and
      was effective for maintaining the open space and recovery of oral functions. The
      secondarily seated resin-bonded FPD, which was made of silver-palladium-copper
      gold alloy and bonded with a primer for noble alloys (V-Primer) and an adhesive
      resin (Super-Bond Opaque), has been functioning satisfactorily for more than 5
      years. This two-stage procedure is useful in situations that require conservative
      or periodontal treatment before seating final prostheses.

PMID- 9656171
TI  - Posterior resin-bonded fixed partial denture with a modified retentive design: a
      clinical report.
AB  - A uncomplicated clinical procedure to enhance the retention of posterior resin
      bonded fixed partial dentures was described. This method involves some
      modifications to the preparation and casting design and requires slightly more
      time and attention at the cementation stage of the prosthetic treatment.

PMID- 9656172
TI  - Temperature response in the pulpal chamber during ultrahigh-speed tooth
      preparation with diamond burs of different grit.
AB  - STATEMENT OF PROBLEM: Ultrahigh-speed tooth preparation can traumatize the hard
      dental tissues and the dental pulp. PURPOSE: This in vitro study examined the
      relationship between different grits of diamond burs on the temperature response
      within a pulpal chamber during tooth preparation with a turbine. MATERIAL AND
      METHODS: Newly extracted, undamaged third molars were secured by a rapid
      tensioning device mounted on an air-supported slide. NiCrNi thermocouples were
      inserted apically and used to determine the temperature within a pulpal chamber.
      The grinding tests used cylindrical fine, coarse, and ultracoarse diamond burs.
      RESULTS: The maximal temperature elevation within the pulp was 3.2 degrees C, and
      the most pronounced rise in temperature occurred with ultracoarse burs.
      Temperature increases in the pulpal chambers and grinding times or temperatures
      of the cooling water were approximately proportional. Residual dentinal thickness
      was inversely proportional to temperature elevation within the pulpal chamber.
      CONCLUSIONS: This study demonstrated that coarse diamond burs resulted in more
      pronounced temperature increases within the pulpal chamber during tooth
      preparation. In addition, the benefit of short intervals between grinding steps
      and a cooling water temperature between 30 degrees C and 32 degrees C was
      confirmed. A cooling temperature of 38 degrees C to 43 degrees C did not afford
      actual cooling.

PMID- 9656173
TI  - Effect of enamel and dentin surface wetness on shear bond strength of composites.
AB  - PURPOSE: This study investigated the effect of the wetness of human enamel and
      dentin surfaces on the shear bond strength of composites. MATERIAL AND METHODS:
      Seven dentin bonding systems were used. Three methods of preparing the enamel or
      dentin surface before applying primer or bonding agent were adopted as test
      conditions: wet (blot dried), semidry (3-second air blast), and dry (15-second
      air drying). Shear bond strength was measured with a universal testing machine.
      Mean bond strengths were analyzed with analysis of variance and Scheffe's F-test.
      Enamel and dentin surfaces were observed by a dissecting microscope after shear
      bond testing. RESULTS: Enamel specimens tested by all systems and dentin tested
      by two systems did not reveal significant differences in shear bond strengths (p
      > 0.05). Among dentin specimens tested by two systems with water-based primers,
      the shear bond strength values of the dry technique group were higher than those
      of the other two groups (p < 0.05). However, among dentin specimens tested by
      systems having acetone-based primers or bonding agents, bond strength values of
      the wet or semidry technique groups were higher than those of the dry technique
      group (p < 0.05). CONCLUSION: It was concluded that some water might be needed by
      dentin surfaces or for primers to obtain high bond strength on the dentin
      surface, but that drying methods did not affect bonding strength to enamel
      surfaces either before priming or after conditioning.

PMID- 9656174
TI  - The effect of tin-electroplating on the bond of four dental alloys to resin
      cement: an in vitro study.
AB  - STATEMENT OF THE PROBLEM: Nickel-chromium alloys are indicated for the
      construction of resin-bonded fixed partial dentures; however, the potential
      toxicity of nickel has been a source of concern. Composite cements do not develop
      an adequate bond to air abraded noble alloys, which cannot be electrolytically
      etched. Tin-electroplating of noble alloys appears to be an alternative treatment
      for resin bonding. PURPOSE: This in vitro study investigated the effect of tin
      electroplating on the bond of a composite cement to base and noble alloys.
      MATERIAL AND METHODS: Tensile tests were made with disks of four alloys that were
      cemented to each other with an adhesive composite cement after (1) air abrasion
      with 50 microns aluminum oxide and (2) air abrasion plus tin-electroplating.
      RESULTS: Tin-electroplating increased the bond strength of metal-ceramic gold
      alloy (Au,Pd,Pt) to a level comparable to the nickel-chromium alloy, but had a
      harmful effect on type IV gold alloy. CONCLUSIONS: Despite the recommendation for
      tin-electroplating of type IV gold alloys, this procedure did not improve bond
      strength to composite in this study.

PMID- 9656175
TI  - In vitro study of the number of surface defects in monophase and two-phase
      addition silicone impressions.
AB  - STATEMENT OF PROBLEM: Monophase addition-cured silicone impression materials in
      stock trays are considered to be alternatives to two-phase systems used with
      custom trays. PURPOSE: This study compared the number of surface defects in
      addition-cured silicone impressions recorded with monophase materials in stock
      trays and two-phase impressions in custom trays. METHODS: The number of voids
      visible on the surface of impressions recorded in vitro were counted. Two
      monophase impression materials. (President Monobody system 75, Bayer Cutter) in
      stock trays were compared with impressions recorded with two-phase addition
      silicone materials (President Plus light-body/regular-body and Zhermack Elite
      light-body/medium-body) in custom trays. A total of 200 automixed impressions, 50
      with each material, were recorded of 50 dentoform molar teeth prepared for full
      veneer crowns. Impressions were examined for surface voids anywhere on the
      prepared part of the tooth by a trained examiner. RESULTS: Mean number of voids
      observed for the monophase impressions were 3.0 +/- 2.2 for President Monobody
      system and 3.4 +/- 2.0 for Bayer Cutter system. Mean number of voids for the two
      phase materials were 0.8 +/- 1.0 for President Plus, and 1.0 +/- 1.1 for Zhermack
      Elite. No significant differences were observed for number of voids between the
      monophase materials or between the two-phase systems (ANOVA and Neuman-Keuls p >
      0.05). However, both two-phase materials in custom trays had significantly fewer
      surface voids than the two-monophase materials (ANOVA and Neuman-Keuls, p <
      0.001) used in stock trays. CONCLUSION: Monophase addition-cured impression
      materials in stock trays carries an increased risk of void formation on the
      surface of the impression when compared with two-phase addition silicone
      materials in custom trays.

PMID- 9656176
TI  - Treatment outcomes with mandibular removable partial dentures: a population-based
      study of patient satisfaction.
AB  - STATEMENT OF PROBLEM: Little is known about the outcomes of treatment with
      mandibular removable partial dentures provided by dentists in private dental
      practice. PURPOSE: This study examined 15 aspects of patient satisfaction and
      explored the factors found to be associated with dissatisfaction. MATERIAL AND
      METHODS: A questionnaire was mailed to people whose dental insurance claims
      included CPT Code 5214 within the last 5 years. A composite measure of treatment
      outcome was created by combining the responses to the 15 satisfaction items, and
      10 factors were then tested statistically to determine their relationship to
      dissatisfaction. RESULTS: A majority of the respondents were satisfied with the
      prosthesis, but a substantial amount of dissatisfaction existed. Dissatisfaction
      was greater when there was no previous wearing experience or when there was an
      opposing maxillary removable partial denture. Respondents under the age of 60
      expressed more dissatisfaction than did those over the age of 60, and subjects
      with lower levels of general health also reported less satisfaction. One third of
      the respondents believed their prosthesis required adjustment or replacement, and
      one fourth said the removable partial denture had caused a problem with the
      natural teeth. CONCLUSION: A majority of survey respondents treated with a
      mandibular removable partial denture in private dental practice were satisfied
      with the prosthesis, but a substantial amount of dissatisfaction existed.
      Dissatisfaction was related to age, health, prior experience with a prosthesis,
      and the type of opposing dentition.

PMID- 9656177
TI  - Evaluation of resilient abutment components on measured strain using dynamic
      loading conditions.
AB  - STATEMENT OF PROBLEM: Factors that affect transmission of strain from prostheses
      to bone may affect the long-term success of loaded implants. Current in vitro
      models are theoretically predictive (finite element modeling) or facsimile
      (photoelastic) in nature. A more clinically relevant in vitro model for strain
      evaluation should be investigated. PURPOSE: This study attempted: (1) to validate
      a human cadaver bone model for vitro measurement of cortical bone strain, and (2)
      to evaluate the effect on cortical strain measurements of a resilient plastic
      component incorporated within a titanium implant in response to variable dynamic
      loading. MATERIAL AND METHODS: Two IMZ (Interpore International) abutment
      alternatives were used: the titanium Abutment Complete and the polyoxymethylene
      Intra-mobile Element. The model system consisted of two implants placed in
      unfixed human cadaver ulna bone to simulate an implant bound edentulous region.
      Four biaxial rosette strain gauges simultaneously recorded cortical bone strain
      immediately mesial and distal to each implant. During experimentation a simulated
      prosthetic framework supported by either titanium or polyoxymethylene abutments
      was dynamically loaded 6 min from the terminal abutment along a cantilever
      extension. Cyclic nominal peak loads were applied with a materials testing
      machine at 20-N intervals from 20 to 200 N at a crosshead speed of 5 mm/minute.
      The protocol allowed frequency of load application to vary. A Newtonian linear
      correlation (r2 > or = 0.98) between load application and strain output was
      determined for each gauge position except for the terminal gauge located opposite
      the cantilever. RESULTS: Cortical strains recorded were within reported
      physiologic ranges involved in bone modeling and remodeling. Further, the
      polyoxymethylene abutment components did not result in reduction of peak
      microstrain at any gauge position. The Intra-mobile Element abutments, however,
      did increase the time required to complete 10 loading cycles when compared with
      the titanium Abutment Complete abutments for the crosshead speed and ultimate
      loads evaluated. CONCLUSIONS: Results indicate the cadaver bone behaved in an
      elastic manner within the load range evaluated, and as such represents a viable
      in vitro experimental model. Under these conditions, polyoxymethylene abutment
      components do not affect measurable bone strain in response to variable loading
      when compared with titanium.

PMID- 9656178
TI  - A method for quantifying complete denture quality.
AB  - STATEMENT OF PROBLEM: Reproducible and quantitative clinical evaluation of
      complete denture prostheses is of great importance for preoperative diagnosis,
      treatment planning, and assessment of quality of denture treatment. PURPOSE: This
      study attempted (1) to clarify the degree of contribution each clinical factor
      made to the general assessment of experienced prosthodontists to complete denture
      prostheses, and (2) to develop a method for quantitative assessment of complete
      denture quality. METHODS: Sixteen clinical factors with a three-grade scale were
      used to evaluate complete denture prostheses in 320 patients. The general
      assessment of the dentures was conducted with a 10-point scale. The contribution
      of each grade of the 16 factors to the general assessment level was determined by
      a multiple regression analysis. RESULTS: Seven factors were highly correlated to
      the general assessment. On the basis of these significant contributions, a
      complete denture scoring method was established followed by the calculation of
      the category scores of these factors and conversion of the total sum of each
      category score to an integer number between 0 and 100. The resultant
      quantification score was closely correlated with the general assessment of the
      denture. CONCLUSION: An evaluation protocol used for scoring of complete dentures
      was developed based on the scientifically analyzed knowledge of experienced
      prosthodontists.

PMID- 9656179
TI  - Alternate framework designs for removable partial dentures.
AB  - STATEMENT OF PROBLEM: The removable partial denture is usually less appreciated
      than the fixed partial denture by both patients and prosthodontists. This
      negative attitude could be due to problems associated with the wearing of a
      removable partial denture and concern essentially with comfort, esthetics,
      masticatory function, occlusal stability, and maintenance of oral hygiene. Such
      problems could be limited if treatment planning is made carefully, according to
      simplified and logical principles for framework design, and if oral hygiene and
      the fit of the dentures are regularly controlled. PURPOSE: This article reviews
      the factors associated with the prognosis of treatment with removable partial
      dentures. Furthermore, the article describes framework design applied in
      different clinical situations and compares them with more conventional designs.
      It seems important to consider a framework design that privileges comfort,
      esthetics, and oral hygiene rather than to follow mechanical rules that are
      entirely theoretical and have not been confirmed scientifically or clinically.

PMID- 9656180
TI  - Pattern of occlusal contacts in lateral positions: canine protection and group
      function validity in classifying guidance patterns.
AB  - STATEMENT OF PROBLEM: The concept of canine protection and group function lack
      consistency in the definitions and examining methods, and a valid system for
      evaluating and classifying occlusal contact patterns has not been established.
      PURPOSE: This study assessed the use of canine protection and group function in
      classifying occlusal guidance in the natural dentition. MATERIAL AND METHODS:
      Occlusal contacts of 86 young adults were examined with shim stock in regulated
      lateral positions, 0.5,1,2 and 3 mm from the maximum intercuspation. The patterns
      of occlusal contacts varying with the lateral position were described. RESULTS:
      Focusing on the working-side contact only, most contact patterns belonged to
      group function, and a few to canine protection. Focusing on both the working and
      nonworking side contacts, nearly half the contact patterns were those other than
      canine protection and group function and were classified into balanced occlusion.
      CONCLUSION: The validity of the classification system using canine protection and
      group function is questionable. A new classification system of occlusal guidance
      is desirable.

PMID- 9656181
TI  - The effect of pretreatment with an oxalic acid solution on marginal adaptation to
      enamel in vivo.
AB  - STATEMENT OF PROBLEM: New acids such as oxalic acid have been introduced as a
      conditioning agent in the total-etch technique. There is concern about long-term
      retention of the acid on enamel in relation to the superficial etch effect.
      PURPOSE: This in vivo study evaluated the marginal adaptation to enamel
      conditioned with either and oxalic acid solution or a phosphoric acid with SEM
      replica technique. MATERIAL AND METHODS: Twenty-four patients received one of
      each of three class III restorations. Two cavity preparations were pretreated
      with aluminum nitrate/oxalic acid/glycine solution 1 of the Gluma 2000 system.
      The first cavity was primed and sealed with Gluma 2000 solution 2, the second
      cavity with Gluma 3 and 4. The third cavity was conditioned with phosphoric acid
      (Gluma 1) and sealed with the bonding resin Gluma 4. All three cavities were
      restored with a hybrid resin composite (Pekafill). At baseline and after 1 year,
      replica impressions were made to study the margins with SEM. Semiquantitative
      analysis of the enamel interfaces was performed (x200 and x1000 magnifications).
      Marginal quality of the three restorative systems were compared and tested
      intraindividually. RESULTS: The three restorations exhibited good enamel marginal
      adaptation and a high percentage of gap-free margins at baseline, 96% to 97% of
      the total length of margins investigated. Marginal quality decreased
      significantly after 1 year for all three groups. Gap-free margins were observed
      in 81% to 85% of the marginal length. No significant differences were found among
      the groups. CONCLUSION: Despite a less pronounced etch pattern created by
      conditioning of enamel with the oxalic acid solution, a good enamel marginal
      quality was observed at both evaluation times, comparable to the marginal
      adaptation of the phosphoric acid conditioned cavities.

PMID- 9656182
TI  - Annual review of selected dental literature: report of the Committee on
      Scientific Investigation of the American Academy of Restorative Dentistry.

PMID- 9656183
TI  - Tooth position index for the fabrication of a mandibular implant-supported
      overdenture bar.
AB  - This article describes an index for the fabrication of a mandibular implant
      supported overdenture bar. The index is a two-piece mold made from an addition
      silicone putty material. It is used to record and maintain the relative position
      of the morphologic contours of the trial denture to the master cast. The split
      mold design permits direct visualization of the amount of space available for the
      design of the retentive bar from both the facial and lingual aspects while
      ensuring room for an adequate thickness of the denture base resin, without the
      need to remove the teeth from the trial denture wax-up.

PMID- 9656184
TI  - The new removable denture patient: treatment procedures.
AB  - Dentists are beginning to see a new type of patient who requires removable
      prosthodontic rehabilitation. These patients are the result of both increases in
      longevity and dental treatment that has retained teeth, despite the onslaught of
      caries and periodontal disease. The current procedures for transitioning patients
      into removable prostheses can be modified for this new group of patients. This
      article presents a transition procedure for patients who are receiving removable
      prostheses, which dissociates the surgical phase of treatment from the prosthetic
      stage. The patient's existing teeth are incorporated into a removable prosthesis
      in a way that ensures the exact replication of the tooth position in the oral
      cavity. This method addresses many of the inadequacies of current procedures
      while at the same time requiring a minimum of chair time. Even with this
      procedure, this transition is still difficult for the patient.

PMID- 9656185
TI  - 1997 Judson C. Hickey Scientific Writing Awards. An innovative investment method
      for the fabrication of a closed hollow obturator prosthesis.
AB  - An investment method is described for fabrication of a closed hollow obturator
      based on the use of three sections of a denture processing flask. The thickness
      of the obturator portion is minimized and all surfaces exposed to the oral cavity
      are processed with heat-polymerized acrylic resin. The technique eliminates
      additional steps noted in the literature, allowing for the prosthesis to be
      processed to completion from the wax trial denture. This technique provides a
      lightweight and seamless obturator and can be used for complete or partially
      edentulous cases. Clinical and laboratory time are minimized while fabricating a
      durable, virtually water-tight prosthesis that can be used alone or in
      conjunction with an extraoral prosthesis.

PMID- 9656186
TI  - A new approach to fabricating the occlusal surfaces of removable prostheses.
AB  - A procedure is introduced to fabricate the occlusal surfaces of removable
      prostheses that oppose ceramic restorations or ceramic denture teeth. It involves
      the use of a heat-processed glass ceramic material in the form of onlays over the
      plastic denture teeth. This procedure provides for more wear compatibility,
      improved esthetics, and individualized occlusion.

PMID- 9656187
TI  - Cell transformation assay: a surrogate for cancer risk?

PMID- 9656188
TI  - Gut transfer and doses from environmental plutonium and americium.

PMID- 9656189
TI  - Transformation of C3H 10T1/2 cells by low doses of ionising radiation: a
      collaborative study by six European laboratories strongly supporting a linear
      dose-response relationship.
AB  - For the assessment of radiation risk at low doses, it is presumed that the shape
      of the low-dose-response curve in humans for cancer induction is linear.
      Epidemiological data alone are unlikely to ever have the statistical power needed
      to confirm this assumption. Another approach is to use oncogenic transformation
      in vitro as a surrogate for carcinogenesis in vivo. In mid-1990, six European
      laboratories initiated such an approach using C3H 10T1/2 mouse cells. Rigid
      standardisation procedures were established followed by collaborative
      measurements of transformation down to absorbed doses of 0.25 Gy of x-radiation
      resulting in a total of 759 transformed foci. The results clearly support a
      linear dose-response relationship for cell transformation in vitro with no
      evidence for a threshold dose or for an enhanced, supralinear response at doses
      approximately 200-300 mGy. For radiological protection this represents a large
      dose, and the limitations of this approach are apparent. Only by understanding
      the fundamental mechanisms involved in radiation carcinogenesis will further
      knowledge concerning the effects of low doses become available. These results
      will, however, help validate new biologically based models of radiation cancer
      risk thus providing increased confidence in the estimation of cancer risk at low
      doses.

PMID- 9656190
TI  - Transfer across the human gut of environmental plutonium, americium, cobalt,
      caesium and technetium: studies with cockles (Cerastoderma edule) from the Irish
      Sea.
AB  - Our previous studies have indicated lower values of the gut transfer factor ('f1
      values') for plutonium and americium in winkles (Littorina littorea) than adopted
      by ICRP. The present study was undertaken primarily to investigate whether this
      observation extends to other species. Samples of cockles (Carastoderma edule)
      from Ravenglass, Cumbria were eaten by volunteers who provided 24 h samples of
      urine and faeces. Urine samples indicated f1 values for cockles which were higher
      than for winkles; for plutonium these ranged overall up to 7 x 10(-4) with an
      arithmetic mean in the range (2-3) x 10(-4), and for americium up to 2.6 x 10(-4)
      with an arithmetic mean of 1.2 x 10(-4). Limited data based on volunteers eating
      cockles from the Solway suggest that f1 values for americium may be greater at
      distance from Sellafield. The measured values compare with 5 x 10(-4) used by the
      ICRP for environmental forms of both elements, which would appear to provide
      adequate protection when calculating doses from Cumbrian cockles. Data for other
      nuclides were obtained by analysing faecal samples from the volunteers who ate
      the Ravenglass cockles. Cobalt-60 showed an f1 value in the region of 0.2, twice
      the value currently used by ICRP. For 137Cs, variabilities were indicated in the
      range 0.08 to 0.43, within the ICRP value of f1 = 1.0. Technetium-99 gave f1
      values up to about 0.6, in reasonable conformity with the ICRP value of 0.5.

PMID- 9656191
TI  - Discharges of krypton from Sellafield, 1951-1997, and the resultant doses to
      members of the public.
AB  - The radionulide 85Kr, which has a half-life of 10.72 years, is produced, almost
      exclusively, by reprocessing operations during which the fission product is
      released from irradiated nuclear fuel by chemical dissolution. Reprocessing
      plants at Sellafield, in Cumbria, have released the noble gas to atmosphere since
      operations commenced in 1952. Historically, krypton discharges were classified
      for security reasons, although these have been monitored and published by BNFL
      for each year since 1977. This paper reviews discharges of 85Kr from Sellafield,
      and consequent radiation doses, since its earliest operations. Over the past
      three years, discharges of 85Kr have increased due to the operation of the
      Thermal Oxide Fuel Reprocessing Plant (Thorp). Nonetheless, the associated annual
      committed effective dose to individuals remains low, peaking around 1.5 microSv a
      1 to the identified critical groups, which compares with typical annual committed
      effective doses from natural sources of radiation of 2200 microSv. Maximum
      collective doses predicted from any single year of operations are 0.6 man Sv, 2
      man Sv and 42 man Sv to the UK, Europe and the world respectively. Comparison may
      be made to natural background committed effective doses, which are of the order
      of 130,000 man Sva-1, 750,000 man Sva-1 and 13,000,000 man Sva-1 to the UK, EU
      and world populations respectively.

PMID- 9656192
TI  - A review of the cost effectiveness of radon mitigation in domestic properties in
      Northamptonshire.
AB  - The costs of remedial work, and the radon level reduction achieved, have been
      studied in a series of domestic properties in Northamptonshire, which is a radon
      affected area. The cost-effectiveness of the series is similar to published
      theoretical estimates for proposed national remediation programmes, and five
      times more effective than our similar analysis for the National Health Service
      workplace, if it is assumed that 100% of householders discovering levels above
      300 Bq m-3 implement remediation. In practice, in the UK, far fewer of those who
      arrange an initial radon test proceed to remediation, but this domestic programme
      could be cost effective if more than 5% carry out remediation. Our series
      confirms that a considerable number of householders with radon levels in the 200
      to 300 Bq m-3 range do not seek or implement remediation work.

PMID- 9656193
TI  - Development of revised Ionising Radiations Regulations.
AB  - New standards in ICRP60 led to the revision of the 1980 European Basic Safety
      Standards Directive, which in turn has created the necessity to revise the
      Ionising Radiations Regulations 1985. Proposals from the Health and Safety
      Commission (HSC) for revised regulations are currently out for public
      consultation in a formal Consultative Document. This article describes some of
      the background to the proposals in the Consultative Document, key influences on
      the revision process and the methods used to develop the proposal so that they
      are broadly acceptable to stakeholders. Some of the changes proposed are
      structural in nature, such as integration of the provision of the Outside Workers
      Regulations. Others are of a legal nature and include: new proposals for
      justification, prior authorisation and risk assessment; two options for the dose
      limitation system; and significant changes to the means of recognising the
      competence of the Radiation Protection Adviser. Following the current public
      consultation, final proposals need to be drawn up, approved by HSC and cleared
      through the European Commission under procedures required by the Euratom Treaty.
      If all goes according to plan, the revised regulations should be on the Statute
      Book about the middle of next year, with most provisions coming into force on 1
      January 2000.

PMID- 9656194
TI  - The European Directive on health protection of individuals against the dangers of
      ionising radiation in relation to medical exposures (97/43/EURATOM).
AB  - On 30 June 1997 the Council of Ministers approved the Directive on the Health
      Protection of Individuals in relation to Medical Exposures (MED) (97/43/EURATOM).
      This MED must be implemented in national law no later than 13 May 2000, repealing
      at that time Directive 84/466/EURATOM, the so-called 'Patient Directive'. It
      complements the Basic Safety Standards Directive of 1996 (96/29/EURATOM) as
      regards medical exposures, which comes into force at the same date. The MED
      considerably extends the scope of application from exposures of patients to all
      exposures directly or indirectly related to medical uses of ionising radiation.
      The MED reaffirms the objectives of the 1984 Directive--to aim at optimum
      diagnostic efficacy at reasonable dose to the patient and to reduce the number of
      unnecessary and inadequate exposures--but also strengthens most of its
      requirements as a result of the experience gained with its implementation and, at
      the same time, adds new provisions considered important taking into account
      scientific and technical evolution in the radiological field. In particular those
      exposures where there is no direct health benefit for the person undergoing the
      exposure and exposures at great risk are given special attention. With the aim of
      facilitating the implementation of the MED in national legislation the European
      Commission, with the help of the group of experts established under article 31 of
      the EURATOM Treaty, will produce technical guidelines with further explanation on
      some of the requirements of the MED.

PMID- 9656195
TI  - Lasers in places of public entertainment.

PMID- 9656196
TI  - [Comparison of chemotherapy CHOP vs. CHOP/VIA in the treatment of aggressive non
      Hodgkin's lymphoma: a randomized multicenter study of 132 patients. The PETHEMA
      group. Program for Study and Therapeutics of malignant hemopathies. Spanish
      Association of Hematology and Hemotherapy].
AB  - BACKGROUND: To compare standard chemotherapy CHOP (cyclophosphamide, adriamycin,
      vincristine and prednisone) with the regimen CHOP/VIA (VP-16, iphosphamide and
      cytarabine) in terms of response to therapy, response duration, survival and
      toxicity in patients with aggressive lymphoma. PATIENTS AND METHODS: 132 patients
      (84 males and 48 females; median age, 55 years) were included from 12 Spanish
      Institutions, diagnosed of non-Hodgkin's lymphoma of intermediate or high grade,
      in stages II-IV and previously untreated. Patients were randomized to receive
      CHOP or CHOP/VIA. RESULTS: After excluding 14 not assessable cases, 62 patients
      (52.5%) received CHOP, and 56 (47.5%) CHOP/VIA. No significant differences were
      found on main prognostic factors between such groups. Response was assessable in
      114 cases (CHOP: 61; CHOP/VIA: 53) 39 patients (64%) receiving CHOP achieved
      complete response (CR), and 2 (3%) partial response (PR), whereas in the CHOP/VIA
      group CR and PR rates were 63% (34/53), and 7% (4/53), respectively. 14 patients
      (36%) treated with CHOP and 12 (35%) treated with CHOP/VIA eventually relapsed,
      with an actuarial risk of relapse at 36 months of 43% and 40%, respectively.
      Median survival was 37 months. No differences were found between both therapeutic
      groups, with an overall survival at 36 months from diagnosis of 53.5% (CI 95%: 40
      67) for CHOP and 48% (CI 95%: 34-62) for CHOP/VIA. Finally, toxicity was not
      different for both arms. CONCLUSION: In the present study in patients with
      aggressive NHL chemotherapy regimens CHOP and CHOP/VIA showed similar results in
      terms of response, response duration, survival and toxicity.

PMID- 9656197
TI  - [Plasma homocysteine levels in patients with ischemic cerebral infarction].
AB  - BACKGROUND: Moderate hyperhomocysteinemia is an independent risk factor for
      stroke. The relationship between homocysteinemia and stroke and its related
      factors are unknown in Spain. PATIENTS AND METHODS: We determined plasma
      homocysteine concentrations in 80 stroke patients and in 48 control subjects
      without vascular risk factors. Folate, vitamin B12 and creatinine concentrations
      were also measured in stroke patients. RESULTS: Total plasma homocysteine
      concentrations were higher in stroke patients compared to controls (11.2 [SD 3.2]
      mumol/l versus 8.1 [2.6] mumol/l; p < 0.001). Hyperhomocysteinemia was present in
      20% of patients and in 2.2% of controls (odds ratio [OR] = 5.75; 95% CI = 1.24
      53.4; p < 0.01). Homocysteine values were related to vitamin B12 (r = 0.28; p <
      0.05) and creatinine concentrations (r = 0.24; p < 0.05). Multiple regression
      analysis showed that about 15% of the variation in plasma homocysteine
      concentrations could be predicted by the values of vitamin B12 (p < 0.001) and
      creatinine (p < 0.05). Homocysteine values were unrelated to age, sex, folate
      concentrations, atherosclerotic subtype or to the presence of vascular risk
      factors. CONCLUSIONS: Moderate hyperhomocysteinemia was present in about 20% of
      stroke patients in our series. Homocysteine plasma level was not related with
      other stroke risk factors or with the atherosclerotic subtype of stroke, but it
      was partially related with the renal function parameters and the serum levels of
      vitamin B12.

PMID- 9656198
TI  - [Availability, use and cost of antidotes in Catalonia].
AB  - BACKGROUND: To know the availability of antidotes in hospital and extra-hospital
      emergency services in Catalonia (Spain), their real use, and the cost. PATIENTS
      AND METHODS: Availability was studied by means of a transversal questionnaire
      carried out in 24 hospitals and 3 extra-hospital emergency services in Catalonia;
      the real use of antidotes was investigated using a prospective study carried out
      for one year in the same 24 hospitals, and the cost was determined using the data
      obtained over 12 months in one large hospital. RESULTS: Average availability was
      35 antidotes in hospital and 13 in extra-hospital emergency services. In no
      service did the availability coincide exactly with that of another service, nor
      with the recommendations made by international institutions (World Health
      Organization and International Programme for Chemical Safety) or the Government
      of Catalonia. The low incidence of availability of antidotes to cyanide was
      notable. Antidotes were used in 12.9% of acute intoxications. In 167 cases
      treated with these drugs, only 9 different antidotes were used. The consumption
      of these antidotes represents 0.1% of the budget of a pharmacy service in one
      large hospital. CONCLUSIONS: The availability of antidotes in Catalonia is
      heterogeneous and some services lack antidotes whose use is considered essential.
      Antidotes are scarcely used in acute intoxications and their economic cost is
      low.

PMID- 9656199
TI  - [Treatment of aggressive non-Hodgkin's lymphomas].

PMID- 9656200
TI  - [Chaos and medical prediction].

PMID- 9656201
TI  - [Molecular cardiology: toward gene therapy].

PMID- 9656202
TI  - [A 37-year-old woman with deafness, decrease of visual acuity, dysarthria,
      myoclonus and changes in eye movements of a 20-year evolution
      (clinicopathological conference)].

PMID- 9656203
TI  - [Optic neuritis and the risk of development of multiple sclerosis].

PMID- 9656204
TI  - [Hepatic toxicity and amlodipine].

PMID- 9656205
TI  - [The miracle of melatonin in Spain].

PMID- 9656206
TI  - [Teaching of clinical nutrition in Spain].

PMID- 9656207
TI  - [Effects of dietary fat saturation on levels of plasma lipoprotein (a) and
      lipids].
AB  - BACKGROUND: Lipoprotein (a) (Lp[a]) is a known risk factor for coronary heart
      disease. Lp(a) plasma concentration mainly depends on genetic polymorphism. The
      aim of this study was evaluate the effect of dietary fat saturation on Lp(a)
      plasma concentration. SUBJECTS AND METHODS: Forty two subjects (eighteen women
      and twenty four men) were placed in four consecutive 5 weeks diet periods. Energy
      intake from proteins, carbohydrates and fats was constant during the study and
      there were only changes on fatty acids composition. First period was enriched in
      saturated fatty acids (SFA), second period in monounsaturated fatty acids (MUFA)
      and third and fourth periods were enriched in polyunsaturated fatty acids (PUFA).
      Fourth period was also enriched in PUFA n-3 (blue fish). RESULTS: Changes on
      dietary fat saturation had a significant effect on plasma lipids and
      lipoproteins. Lp(a) plasma concentration was minimum in SFA phase (6.8 [SD 7.3]
      mg/dl), increasing during MUFA phase (8.7 [8.5] mg/dl) and was maximum in PUFA n
      6 and PUFA n-3 (11.5 [11.1] and 12.7 [11.9] mg/dl, respectively) (p < 0.0001).
      CONCLUSIONS: Changes on dietary fat saturation significantly modify Lp(a) plasma
      concentration. These variations went in opposite direction to LDL-cholesterol
      modifications and were clinically irrelevant.

PMID- 9656208
TI  - [Genetic polymorphism of vitamin D receptor and osteoporosis].
AB  - BACKGROUND: Genetic factors condition an important part of bone mass. The role of
      vitamin D receptor polymorphism (VDR) as genetic marker of osteoporosis is a
      matter of discussion. We have studied the possible influence of VDR on bone
      remodelling, calciotropic hormones, on the presence of osteoporosis and
      osteoporotic bone fractures. PATIENTS, CONTROL POPULATION AND METHODS: A case
      control study. We have studied a total of 127 postmenopausal Canarian women from
      Canary Islands, Spain; 66 healthy controls and 61 with the diagnosis of
      osteoporosis, which was made by clinical, radiological and densitometric
      criteria. 17 osteoporotic women have had a fracture: Colles, hip or vertebral
      (spinal deformity index) fracture. VDR were determined by PCR directed to
      demonstrate the presence (b) or absence (B) of a restriction target for Bsml in
      intron 7. We analyzed some biochemical markers of bone remodelling: serum levels
      of alkaline phosphatase, tartrate resistant acid phosphatase and urine ratios of
      calcium/creatinine and hydroxyproline/creatinine. We also determined calciotropic
      hormones: parathyroid hormone and calcitonin. Bone mass was measured by DEXA and
      TC. RESULTS: There were no significant differences in either biochemical bone
      remodelling markers or in bone mass between the three genotypes: bb, Bb and BB,
      either in controls or in osteoporotic women with the exception of alkaline
      phosphatase which had a significative increase compared to control in women with
      unfavorable alleles distribution (bB and BB). Distribution of genotypes was
      similar between controls and osteoporotic women, with or without fractures.
      CONCLUSIONS: In Canarian women, VDR genotype is not associated with changes in
      biochemical markers of bone remodelling or in bone mass or with the presence of
      osteoporosis or osteoporotic fractures.

PMID- 9656209
TI  - [Epidemiological study on the incidence of inflammatory bowel disease in 4
      Spanish areas. Spanish Group on the Epidemiological Study of Inflammatory Bowel
      Disease].
AB  - BACKGROUND: The incidence of inflammatory bowel disease (IBD) shows marked
      geographical variations. The aim of this study was to determine and compare the
      incidence of IBD in four Spanish areas: Sabadell (Northeast), Vigo (Northwest),
      Mallorca island and Motril (South). PATIENTS AND METHODS: Prospective survey
      based on inception cohorts over a two-years period (1 October 1991 to September
      1993). Subjects were the patients resident in these areas and diagnosed of IBD
      according to a standard protocol for case ascertainment and definition. RESULTS:
      Altogether 328 cases were identified, of whom 191 were diagnosed as ulcerative
      colitis (UC), 135 as Crohn's disease (CD) and 2 as indeterminate colitis. The
      overall adjusted incidence rate per 100,000 persons between ages 15-64 years of
      UC and CD were respectively 9.8 and 5.2 in Sabadell, 7.7 and 5.0 in Vigo, 7.8 and
      5.8 in Mallorca and 4.3 and 6.5 in Motril. The Incidence rate ratio showed no
      significant differences for either conditions among these areas. The global
      adjusted incidence rate of UC in Spanish areas (8.0; IC 95%: 6.3-9.7) was
      significantly lower to that of Northern European countries while that of CD (5.5;
      IC 95%: 4.1-6.9) was between that of Northern and Southern Europe with no
      significant differences. CONCLUSIONS: The incidence of IBD did not show
      differences among the Spanish areas, and rates are between 2 and 6 times higher
      than those previously reported. The incidence of UC is significantly lower than
      that observed in the North of Europe, while for CD the incidence is between that
      of Northern and Southern Europe.

PMID- 9656210
TI  - [How many HIV's are there?].

PMID- 9656211
TI  - [Detection of human herpesvirus 8 in patients with Kaposi's sarcoma or
      Castleman's disease associated with AIDS].
AB  - A new herpesvirus provisionally termed as KSHV or HHV-8 has been detected in
      lesions from AIDS-based Kaposi's sarcoma (KS) and from other KS clinical forms,
      and also in other tumors such as body cavity-based lymphomas or Castleman's
      disease (CD). We have assessed the presence of this novel herpesvirus in
      specimens from patients diagnosed with either AIDS and KS or AIDS and CD. DNA
      samples from skin lesions and peripheral blood obtained from 8 patients diagnosed
      with AIDS, seven with KS and one with multicentric CD were analyzed; skin
      specimens and peripheral blood samples from volunteer blood donors or from KS and
      CD free HIV seronegative patients were used as controls. Detection of the virus
      was done by PCR amplification of KS330 region, one of the HHV-8 sequences first
      reported. All skin lesions analysed tested positive for KS330; peripheral blood
      samples from 5 of the patients, including the one diagnosed with CD, showed also
      the virus sequence. All skin specimens and peripheral blood samples from controls
      were negative. From our results it can be concluded that the novel herpesvirus
      HHV-8 can also be detected in patients with AIDS-associated KS and AIDS
      associated CD in Spain.

PMID- 9656212
TI  - [The truth and its disclosure to the patient].

PMID- 9656213
TI  - [The antioxidant capacity of melatonin: its defensive role against age-related
      diseases].

PMID- 9656214
TI  - [Markers of hepatitis A and B virus infection in workers of a municipal sanitary
      enterprise].

PMID- 9656215
TI  - [Why do research?].

PMID- 9656216
TI  - [Methicillin-resistant Staphylococcus aureus infection in a geriatric unit for
      acutely ill].

PMID- 9656217
TI  - [Behcet's disease and relapsing polychondritis (MAGIC syndrome) associated with
      antiphospholipid syndrome].

PMID- 9656218
TI  - [Sudden decrease of HIV/AIDS mortality in the community of Madrid].

PMID- 9656219
TI  - [Genotypes of hepatitis C virus: their relationship with risk factors, the
      severity of liver disease, and the serologic response].
AB  - BACKGROUND: The objective of our study was to ascertain the prevalence of
      different HCV genotypes between the hepatitis C patients in the health area of
      Monforte de Lemos, Spain, as well as the possible influence of risk factors on
      their distribution and their relation with hepatic disease and with the serologic
      response. PATIENTS AND METHODS: We have studied 128 patients with hepatitis C. Of
      these, 41 were intravenous drug users (IVDU), 19 had received transfusions, 7
      were hemodialyzed and in 61 the risk factors were unknown. Antibodies against HCV
      were detected by second-generation enzyme immunoassay (EIA) and confirmed by
      immunoblot. RNA-HCV presence was studied by reverse transcription-PCR (RT-PCR),
      and a reverse hybridization test of the amplifications was used for the
      genotyping. RESULTS: Hepatitis C genotypes 1b (46.1 [8.6%]), 1a (23.4 [7.3%]) and
      3a (13.3 [5.9%]) were the most frequently encountered genotype. Genotype 1a (48.8
      [15.3%]) was the most prevalent genotypes in IVDU patients, while 1b was the most
      frequent in patients of unknown risk factors (62.3 [12.1%]). Alanine
      aminotransferase (ALT) was elevated in 66.6 (17.7%) of patients with genotype 1a,
      in 87.5 (8.6%) of patients with genotype 1b (p = 0.0367) and in 94.1 (11.2%) of
      patients with genotype 3a (p = 0.0347). Subtype 1b was present in 6 of 7 cases of
      cirrhosis (85.7%) and in 7 of 12 cases of active chronic hepatitis (58.3%). No
      significant statistical differences were observed between the genotypes and the
      specific IgM response against core antigen of HCV, neither we observed
      differences in the serologic response against C1, C2, NS3 and NS4 peptides.
      CONCLUSIONS: Hepatitis C genotypes 1a and 3a were the most prevalent genotypes
      between IVDU patients while genotype 1b was the most frequent between non-IVDU
      patients. Genotype 1b was associated to severe liver disease. Percentage of
      positivity or the reactivity against HCV peptides was independent of the genotype
      encountered in the patient.

PMID- 9656220
TI  - [Factors associated with mortality and gait impairment in elderly patients with
      hip fractures].
AB  - BACKGROUND: Hip fractures are a major source of mortality and morbidity among the
      elderly. The aim of the present study is to try to identify predictors of death
      and of non-deambulation during the period of acute treatment. PATIENTS AND
      METHODS: Consecutive prospective study of 459 patients older than 65 years
      admitted to our hospital with acute proximal femoral fractures with 12 months
      follow-up. RESULTS: The mean length of hospital stay was 26.6 days, it exists a
      highly percentage of non-ambulatory patients at discharge from hospital (44.3%),
      a low percentage of mortality in the immediate postoperative period (6.1%) and a
      larger percentage of mortality at 6 months (26.15%). Factors associated with risk
      of death at hospital are male sex (OR = 2.38; 95% CI = 1.04-5.47), deteriorated
      mental status (OR = 2.62; 95% CI = 1.01-6.76) and no previous personal
      independence (OR = 3.16; 95% CI = 1.19-8.38). Age over 80 years (OR = 2.27; 95%
      CI = 1.43-3.60), deteriorated mental status (OR = 7.90; 95% CI = 3.83-16.3), no
      walking ability before fracture (OR = 3.72; 95% CI = 2.33-5.91) and type of
      fracture (OR = 1.84; 95% CI = 1.15-2.95) are shown as the determinants of gait
      capacity. CONCLUSIONS: Mortality in the immediate postoperative period is
      associated with sex, dementia and previous personal independence. The hospital
      stay is extended and functional recovery at discharge is low, therefore, new
      programs for these patients should be considered.

PMID- 9656221
TI  - [Relationship of increased body weight, androgens, insulin and family history of
      hypertension with blood pressure in premenopausal women].
AB  - BACKGROUND: The aim of this study was to evaluate whether the body weight
      increased, the androgens, the insulin and the family history of hypertension were
      independently associated with hypertension. PATIENTS AND METHODS: Sixty-two
      premenopausal women aged 42 y, whose did not have any situation that change the
      variables to study: blood pressure, body mass index (BMI) and her increase since
      age of 20, waist to hip ratio, family history of hypertension, smoking, alcohol,
      exercise, fasting and after oral glucose tolerance test (GTT) glucose and
      insulin, sex hormone binding globulin (SHBG), serum and salivary testosterone and
      the free testosterone index. Hypertension was defined as blood pressure > or =
      140/90 mmHg. Multivariate analysis and prevalence odds ratio was calculated.
      RESULTS: Diastolic blood pressure correlated positively with BMI, waist to hip
      ratio, increase of BMI, GTT glucose, fasting and GTT insulin, free testosterone
      index and negatively with SHBG. Systolic blood pressure was only positively
      correlated with GTT glucose. Into a logistic regression model, the increase of
      BMI (OR: 1.23; IC: 95%: 1.04-1.5), the family history of hypertension (OR: 7.6;
      IC 95%: 1.9-29.9) and the free testosterone index (OR: 1.7; IC 95%: 1.1-2.6) were
      the only variables independently associated with hypertension. The prevalence
      odds ratio of hypertension according to the presence or not of family history of
      hypertension decreased when highest increase of BMI was considered. CONCLUSIONS:
      Higher free testosterone levels with body weight increased in adulthood and
      family history of hypertension are independent predictors of hypertension in
      premenopausal women, whereas fasting insulin levels may be related to family
      history of hypertension.

PMID- 9656222
TI  - [Creutzfeldt-Jakob disease: an epidemic of the 21st century?].

PMID- 9656223
TI  - [Economic evaluation of drugs: practical applications for the different deciding
      agents].

PMID- 9656224
TI  - [Instrument for the measure of quality of life in cancer patients].

PMID- 9656225
TI  - [76 Year-old woman with tumor in the vertebral cervical spine].

PMID- 9656226
TI  - [Torsade de pointes secondary to treatment with pentavalent antimonial drugs].

PMID- 9656227
TI  - [The use of factorial analysis in the evaluation of transcultural equivalence in
      questionnaires].

PMID- 9656228
TI  - [Carbon monoxide poisoning].

PMID- 9656229
TI  - [Mooren's corneal ulcers associated with hepatitis C].

PMID- 9656230
TI  - Ipidacrine (NIK-247), a novel antidementia, rapidly enters the brain and improves
      scopolamine-induced amnesia in rats during the Morris water maze task.
AB  - The effects of single and repeated administrations of ipidacrine (NIK-247, 9
      amino-2, 3, 5, 6, 7, 8-hexahydro-1H-cyclopenta [b] quinoline monohydrochloride
      monohydrate) on scopolamine-induced spatial learning deficit were investigated in
      rats using the Morris water maze task. A single oral administration of ipidacrine
      (0.3 and 1 mg/kg) reduced the increased total latency induced by scopolamine in
      this task. The repeated administration of ipidacrine (1 mg/kg) of once a day for
      5 successive days reduced the increased total latency induced by scopolamine to
      the levels of the saline-treated control rats in this task. In this pharmaco
      kinetic study, ipidacrine was rapidly taken up into the brain within 5 min.
      Moreover, higher drug levels were observed mainly in the cortex and hippocampus,
      which both play important roles in learning and memory. Thus, a previous study
      together with this investigation indicate that ipidacrine improves amnesia which
      consists of the impairment of the working and reference memory in various animal
      models, suggesting that ipidacrine is a useful candidate for the therapy of
      patients with Alzheimer's disease.

PMID- 9656231
TI  - Effects of early postnatal AF64A treatment on passive avoidance response and
      radial maze learning in rats.
AB  - In order to investigate how the selectively lesioned cholinergic system at the
      early postnatal age influences adult learning behavior, the effects of postnatal
      administration of ethylcholine mustard aziridinium ion (AF64A), a selective
      cholinergic neurotoxin, on the acquisition of 2 kinds of learning tasks were
      examined. Rat pups received an intraventricular injection of AF64A (1.0 or 2.0
      nmol) or saline on postnatal day 8, and in adulthood (at 3 months of age), they
      were tested with the acquisition of passive avoidance response (PAR) and 8-arm
      radial maze learning. In PAR testing, a significant impairment was observed in
      male AF64A-treated rats. In addition, in the radial maze task, AF64A-treated rats
      needed significantly more trials to acquire the task as compared with saline
      treated animals. Histological examination after behavioral testings revealed a
      marked reduction of acetylcholinesterase-stained fibers in the hippocampus and
      dentate gyrus of the AF64A-treated groups, while there were no detectable changes
      in the striatum or cerebral cortex. The results suggest that early postnatal
      AF64A administration induced learning deficits in adulthood which were associated
      with long-lasting cholinergic denervation in hippocampal formation.

PMID- 9656232
TI  - [Pharmacokinetics of haloperidol in patients on hemodialysis].
AB  - Psychotic symptoms among patients receiving hemolytic dialysis (HD) are quite
      common, while studies showing pharmacokinetics and clearances of neuroleptics in
      such patients are few. In such instances, previous studies recommended a single
      administration of neuroleptics with about 1/3 to 1/2 of the normal dose for
      patients without renal failure. We made a study of 4 cases of delirious patients
      receiving HD and investigated the relationship between a daily dose of
      haloperidol (HP), its blood concentration and changes of delirium symptoms before
      and after HD. Oral or intravenous doses of HP (12-24 mg) were required for the
      improvement of delirium. Blood concentration increased in proportion to the HP
      dosage in all patients, and its average was significantly higher than that of the
      control group. Approximately 25% of clearance was found before and after HD.
      These studies suggest that the HP dosage for HD patients needs to be larger than
      previously assumed. Changes in the pharmacokinetics of HP in HD patients seemed
      to be influenced by a variety of factors such as binding rate with blood serum
      albumin and HP, metabolic pathway of HP, and sensitivity of HP in the brain.

PMID- 9656233
TI  - [Mitochondrial benzodiazepine receptors (MBR) in association with neurological
      disorders].
AB  - Ro 5-4864, a specific agonist of the peripheral-type benzodiazepine receptor
      (PBR), elicited convulsions 2.6 times more potently in EL mice (an animal model
      of epilepsy) than in DDY mice (control animal). A binding assay revealed a 50%
      higher density of [3H] Ro 5-4864 binding sites in the mitochondrial fraction
      (i.e., mitochondrial benzodiazepine receptors; MBR) of the brain tissues in EL
      mice as compared with DDY mice. On an elevated plus-maze, EL mice showed fear
      responses similar to those increased in DDY mice after PBR stimulation,
      suggesting a hyperfunction of MBR underlying the abnormal behaviors of EL mice.
      In fluorometric studies using NG108-15 cells, Ro 5-4864 depolarized mitochondrial
      membranes and, possibly as a consequence of this, raised intracellular Ca2+.
      Finally, we propose that MBR could be a major target of therapy for various
      neurological disorders, so drugs such as "mitochondrial membrane stabilizers"
      should be developed.

PMID- 9656234
TI  - [Recent advances in Alzheimer's disease research].
AB  - Vascular dementia (VD) and Alzheimer's disease (AD) are two main causes of
      dementia in the aged. Recent epidemiological studies in Japan indicate that the
      incidence of AD is becoming slightly higher than that of VD. Among various
      approaches to clarify the etiology of AD, research through the mechanism of
      formation of senile plaque and neurofibrillary tangle, which characterize AD
      pathology, seems to be the most orthodox as well as fruitful. Genetic studies on
      hereditary AD reveal that the etiologies of AD are heterogeneous, but the
      deposition of beta amyloid followed by the accumulation of abnormally
      phosphorylated tau-protein seems to be the common process specific to AD. In
      regards to the clinical problems of AD, development of the diagnostic markers for
      early definite diagnosis and effective therapeutic agents is most urgent. The
      index of A beta 40/A beta 42 x tau calculated from measurements of A beta and tau
      levels in cerebrospinal fluid is the best marker at present. On the other hand,
      many antidementia drugs are now on trial. Most of them are acetylcholine
      stimulating agents, including tacrine and donepezil, which have been admitted
      recently in the USA and some other countries. Such drugs which suppress the
      development of AD should be called true antidementia agents, but the present
      drugs are not true antidementia drugs.

PMID- 9656235
TI  - [Motor and cognitive functions of the basal ganglia].
AB  - Basal ganglia have been known as a motor center because their lesions cause motor
      disturbances in involuntary movements such as chorea, ballism or akinesia in
      Parkinsonism. The different types of involuntary movements are closely related to
      the underlying muscle tone. Mechanisms of bradykinesia or akinesia have been
      elaborated in physiological studies on Parkinson's disease, and the significance
      of sensorimotor processing or attention, arousal has been disclosed as a relevant
      factor of bradykinesia. Cognitive functions of the basal ganglia have attracted
      attention, particularly in the disorder of Parkinson's disease. Subcortical
      dementia, difficulty in formation or changes of concepts, is encountered in
      advanced stages of Parkinson's disease. Whether cognitive functions in the
      frontostriatal system are primarily related to the motor function of the brain is
      an issue for future study.

PMID- 9656236
TI  - [Postsurgical adjuvant immunotherapy against primary non-small cell lung cancer].
AB  - The prognosis of lung cancer patients is generally poor even when they have
      undergone complete resection of primary tumors and systemic lymph node
      dissection. This is mainly attributed to micrometastases which have already
      developed by the time of surgery and the fact that local therapies cannot
      eliminate all cancer cells from the body. We developed a multimodality
      combination therapy for primary non-small cell lung cancer consisting of surgery,
      chemotherapy, and adoptive immunotherapy using interleukin 2 (IL-2) and
      lymphokine-activated killer (LAK) cells. The results of a randomized study
      indicated that the survival rate of the IL-2, LAK adoptive immunotherapy group
      was significantly higher than that of the control group. In conclusion, IL-2, LAK
      adoptive immunotherapy is an effective and promising modality which will
      compensate for the deficiencies of other therapies.

PMID- 9656237
TI  - [Therapy for non-small cell lung cancer: new concepts based on molecular
      biology].
AB  - Recent advances in molecular biology have broadened our knowledge of the
      biological characteristics of cancer. In the present paper, we review and discuss
      new modalities of therapy for non-small cell lung cancer (NSCLC) based on
      biological findings. These modalities include: 1) diagnosis of cancer based on
      gene abnormalities: 2) decision making on chemo-/radiotherapy based on new
      biological findings: 3) gene therapy: and 4) new chemotherapeutic agents.
      Mutation of the p53 gene, which occurs most frequently in NSCLC, is a well
      documented molecular target in these modalities. The development of polymerase
      chain reaction technology has enabled early diagnosis of NSCLC by detection of
      p53 gene abnormalities in sputum. Transfer of the wild-type p53 gene using a
      retrovirus vector to cancer tissues with mutant p53 gene has already been tested
      clinically. Inhibition of tumor neovascularization has been studied extensively
      in attempts to develop noveal chemotherapeutic agents. Angiostatin or endostatin,
      an inhibitor of tumor neovascularization is in clinical use. Matrix
      metalloprotease inhibitions (MMPs) also inhibit neovascularization of tumors.
      Marimastat, an oral MMP, is expected to prevent cancer metastasis.

PMID- 9656238
TI  - [Does induction therapy followed by surgery improve the survival rate in limited
      stage small-cell lung cancer patients?].
AB  - Small-cell lung cancer (SCLC) is distinguished from non-small cell lung cancer
      (NSCLC) by its rapid tumor doubling time, high growth fraction, and early
      development of widespread metastases. Surgery alone offers the best chance for
      long-term survival in selected patients with stage I SCLC. Most patients with
      limited SCLC (stage I-IIIa) are treated with "comprehensive therapy" combined
      with chemotherapy, radiotherapy (thoracic radiotherapy and/or prophylactic
      cranial irradiation), and surgery. Although the efficacy of surgery in the
      control of local disease is well established, to date no report has shown better
      survival rates in patients who receive induction therapy when compared with
      patients receiving postoperative chemotherapy. However, studies of induction
      therapy include more patients with advanced-stage cancer than do studies of post
      operative chemotherapy. Thus the final role of induction therapy followed by
      surgery must await the results of future prospective, randomized trials conducted
      by large cooperative study groups.

PMID- 9656239
TI  - [Surgical treatment for metastatic lung tumors].
AB  - Surgical treatment for metastatic lung tumors has been reported to be efficacious
      in selected patients by many authors. Most of these reports are retrospective
      studies. In our hospital, metastatic lung tumors were resected in 624 patients,
      and the 5- and 10-year survival rates after pulmonary metastatectomy were 38.3%
      and 26.6%, respectively. There are many long-time survivors without recurrence
      after thoracotomy. However, pulmonary metastatectomy seems to offer no survival
      benefit in some cancers, e.g., gastric cancer, even if the patients satisfy the
      criteria for surgery. Prospective studies for each type of primary cancer are
      needed to determine the true efficacy of pulmonary metastatectomy.

PMID- 9656240
TI  - [Surgical treatment for multiple bilateral pulmonary metastatic tumors].
AB  - To date, 162 patients with metastatic pulmonary tumors have undergone surgical
      treatment in our institute (93 carcinomas, 51 sarcomas, 17 germ cell tumors, 1
      melanoma). Of these, 57 and 105 had solitary and multiple lesions, respectively,
      at their first surgery. Five of 57 patients developed additional lesions later.
      The incidence of multiple pulmonary metastases was higher in sarcoma than in
      cancer patients, and the prognosis after surgical treatment was found to be
      significantly better in cancer than in sarcoma for patients with multiple
      lesions. However, no significant difference was observed between the survival of
      those with solitary and multiple lesions. The number of lesions found at surgery
      was greater than that calculated based on preoperative chest CT scans, and the
      discrepancy was greater when lesions exceeded 10 in number. However, the increase
      in the number of metastatic lesions found did not affect the surgical results.
      There was also no statistical difference in survival between patients with
      bilateral and unilateral lesions. In contrast, those who underwent complete had a
      significantly better prognosis than those who underwent incomplete resection at
      surgery.

PMID- 9656241
TI  - [Treatment for thymus-related malignant tumors].
AB  - Surgery is the first-line therapy for thymoma. Postoperative radiotherapy should
      be given for all invasive thymomas, followed by chemotherapy in some cases. Even
      if the resection is not complete, surgery is effective therapy because most
      thymomas are local and slow growing. Multidrug chemotherapy including cisplatin
      is effective against thymoma. Thymic cancer is histologically varied. Surgery is
      only one effective therapy for thymic cancer. Although no definitive chemotherapy
      regimen for thymic cancer has yet been established, we feel that the cisplatin,
      doxorubicin, cyclophosphamide, vincristine 4-drug combination regimen is
      effective in thymic cancer patients. Seminoma out of mediastinal germ cell tumor
      (GCT) is expected to have a good prognosis after surgery and radio-/chemotherapy.
      Although the prognosis for those with nonseminomatous GCT has recently improved
      due to chemotherapy and surgery, it is still poor.

PMID- 9656242
TI  - [Treatment of non-thymic malignant tumors of the mediastinum].
AB  - Nonthymic malignant tumors of the mediastinum are quite rare. Primary mediastinal
      malignant lymphomas, malignant mediastinal neurogenic tumors, and primary
      malignant mediastinal mesenchymal tumors are reviewed and discussed in terms of
      the problems in their treatment.

PMID- 9656243
TI  - [Therapeutic strategy for pleural mesothelioma].
AB  - Generally pleural mesothelioma is divided into two histologic types: localized
      and diffuse. Most cases of the former are considered to be benign and the latter
      malignant. The treatment strategy for these tumors has been investigated,
      including various surgical and chemotherapeutic approaches. In spite of these
      efforts. no curative method for malignant mesothelioma has been established yet,
      although the gene therapy is expected to be the most powerful tool in the near
      future.

PMID- 9656244
TI  - [Chest wall reconstruction after resection of malignant chest wall tumors].
AB  - Full-thickness chest wall resection is performed for complete removal of primary
      and secondary malignant chest wall tumors. Large defects of the chest wall after
      resection must be repaired to maintain adequate ventilation, to protect important
      intrathoracic structures, and to preserve cosmetic integrity. Various materials
      have been utilized over the years to replace the rigid chest wall. At present,
      Marlex mesh and a composite of Marlex mesh and methylmethacrylate are frequently
      used to reconstruct rigid chest wall defects. On the other hand, to replace the
      soft part of the chest wall and cover the rigid materials, pedicled muscle flaps,
      myocutaneous flaps, or omentum are used. Major pedicled flaps include the
      pectoralis major, rectus abdominis and latissimus dorsi muscular, and
      musculocutaneous flaps. Techniques are now available to repair any chest wall
      site, and to restore chest continuity in patients whose tumors are curatively
      resected.

PMID- 9656245
TI  - [Functional significance of p53 gene mutation in astrocytic neoplasms].

PMID- 9656246
TI  - [p16 tumor suppressor gene alteration in brain tumors].

PMID- 9656247
TI  - [Abnormalities of the EGF receptor gene in brain tumors].

PMID- 9656248
TI  - [NF2].

PMID- 9656249
TI  - [A puzzle with more pieces?: entering an era with a handful of glioma suppressor
      genes].

PMID- 9656250
TI  - [Vertigo and dizziness related to platelet aggregability].
AB  - Platelet aggregates were measured in 82 cases with vertigo and dizziness and 60
      cases with additional symptom of headache (so-called cervical vertigo). Results
      showed that patients with vertigo and dizziness had increased aggregability and
      patients with cervical vertigo were within normal range (p < 0.0001). 53 cases of
      these with vertigo and dizziness were administrated platelet aggregation
      inhibitors (mainly ticlopidine). After 1 approximately 2 weeks, most of patients
      became symptom free, and at this time platelet aggregates of these patients were
      suppressed to within normal range. Then patients were followed with chronological
      measurements of platelet aggregates. During this time, aggregabilities were
      attempted to be kept within the normal range, thus dose of platelet aggregation
      inhibitor was controlled depending on the result of aggregability. Also patients
      were encouraged to show good drug compliance by being informed of sudden
      increasing aggregability. One patient experienced recurrence of vertigo after
      ceasing the medicine. This study demonstrates that platelet aggregation may
      increase in most of patients with not only vertigo but also dizziness in whom
      administration of a platelet aggregation inhibitor is effective. It also stresses
      that chronological measurements of platelet aggregations are important to control
      the dose of medication.

PMID- 9656251
TI  - [Diffusion-weighted MRI detectability of acute cerebral ischemia: comparison with
      eventual infarction].
AB  - To clarify the clinical significance of diffusion-weighted magnetic resonance
      imaging (DWI) hyperintensity in acute cerebral ischemia, 34 patients were
      investigated with cerebral ischemia that had lasted no more than 8 hours. Either
      a spin echo sequence with navigator echo (n = 21) or an echo planar sequence (n =
      13) was used for DWI using 1.5 tesla magnet. The eventual infarction was judged
      from T2-weighted image (T2 WI) or CT performed 2-12 days after the onset and was
      classified into cortical (n = 24) or perforating artery (n = 10) area. The
      eventual infarction was compared in size with the acute DWI finding and expressed
      as larger, same or smaller. Thirty patients showed ischemic hyperintensity
      lesions on acute DWI (6 patients on T2 WI). In cortical artery areas, the
      eventual infarction was same as hyperintensity area of acute DWI in 15 cases,
      larger in 8 cases, smaller in 2 cases. In perforating artery areas, the eventual
      infarction was same as hyperintensity area of acute DWI in 8 cases, and larger in
      2 cases. These results suggest that in the perforating artery areas, the acute
      DWI hyperintensity is a good predictor of the eventual infarction and that in
      cortical artery areas, dynamic ischemic process may continue for hours before
      resulting in the eventual infarction.

PMID- 9656252
TI  - [Caregiver burden in dementia: evaluation with a Japanese version of the Zarit
      caregiver burden interview].
AB  - BACKGROUND AND PURPOSE: Dementia patients need assistance or supervision in their
      daily activities. This often places a major burden on their caregivers. The
      caregiver burden is reportedly a critical determinant for negative caregiving
      outcomes. However, in Japan, no study evaluating the burden experienced by
      caregivers for patients with established dementia diagnosis with a standardized
      instrument has been carried out. The Zarit Caregiver Burden Interview (ZBI) is a
      standardized, validated, reliable tool for assessment of the burden of caregivers
      for dementia patients, and has been used in many studies in North America. In
      this study, we arranged a Japanese version of the ZBI and applied it to
      caregivers who were caring dementia patients. After examining the reliability and
      validity of this version, we then studied a relationship between patients'
      impairments and caregivers' burden. SUBJECTS AND METHODS: Subjects were 117
      dementia patients. Diagnosis of dementia was made through extensive examinations
      including MRI and PET/SPECT of the brain and based on appropriate clinical
      diagnostic criteria of each disorder, which included Alzheimer's disease (n =
      76), frontotemporal dementia (n = 10), vascular dementia (n = 11), progressive
      supranuclear palsy (n = 3), corticobasal degeneration (n = 5), dementia with Lewy
      bodies (n = 11), and normal pressure hydrocephalus (n = 1). The patients included
      80 women and 37 men; the mean age was 72.3 +/- 7.7 (SD) years. Trained nurses
      interviewed a principal caregiver of each patient by using the ZBI. The
      caregivers included the patients' spouses (n = 62), offsprings (n = 17),
      offspring's spouses (n = 37), and sibling (n = 1). Cognitive, functional, and
      neuropsychiatric impairments and severity of dementia were assessed with
      standardized instruments of the Mini-Mental State Examination (MMSE), Hyogo
      Activities of Daily Living Scale (HADLS), Neuropsychiatric Inventory (NPI), and
      Clinical Dementia Rating (CDR), respectively. RESULTS: The mean total ZBI score
      was 28.6 +/- 15.3 (SD), the Personal strain (PS) score was 17.4 +/- 8.9, and Role
      strain (RS) score was 6.5 +/- 5.7. All three scores had high Cronbach's alpha
      coefficients (Total: 0.88, PS: 0.78, RS: 0.80) and had high Pearson's correlation
      coefficients with a single global rating of burden (Total: 0.69, PS: 0.65, RS:
      0.60). All ZBI scores were significantly correlated with MMSE, CDR, HADLS, and
      NPI scores. A stepwise regression analysis revealed only the HADLS score and NPI
      score as significant predictors of ZBI scores. CONCLUSIONS: This Japanese version
      of the ZBI has a sufficient reliability and validity comparable to those reported
      for the original version. Our results suggested that the patients' functional and
      neuropsychiatric impairments were main patient's factors to increase the
      caregiver's burden.

PMID- 9656253
TI  - [Visual defect due to chiasmic compression by the A1 portion of the anterior
      cerebral artery].
AB  - Unilateral nasal hemianopia is highly difficult to notice with bilateral vision
      intact, and only a few cases has been reported. There are several reported cases
      of quadrantic hemianopsia caused by cerebral lesions, but the defects were found
      bilaterally in all cases. There is only one reported case of which an aneurysm
      was believed to be the cause. We confronted 3 cases of unilateral nasal
      quadrantic hemianopia. In either case no ophthalmologic disorders could be found
      but magnetic resonance imaging revealed the compression of the optic chiasma by
      the A1 portion of the anterior cerebral artery. All three cases are presently
      under conservative therapy and receive routine evaluations. Nerve fibers from the
      upper and lower areas of the retina are routed complicatedly in the optic nerve
      in the periphery of the optic chiasma. From the presentation of the quadrantic
      hemianopia and from the radiological findings, we diagnosed that the visual
      defect was caused by vascular compression of the optic chiasma.

PMID- 9656254
TI  - [High uptake on 11C methionine PET scan in the pituitary gland of a patient with
      cerebral glioma after surgical abortion].
AB  - Positron emission tomography (PET) with various tracers provides physiologic and
      biochemical information of living organs. Since radiologic examinations are
      usually avoided in pregnant women, mainly because of the radiation risk to the
      fetus, little is known about the effect of pregnancy on cerebral blood flow and
      metabolism. This paper reports findings of a 11C methionine PET scan of the
      pituitary gland in a woman after an abortion. The patient was a 31-year-old woman
      who suffered a seizure in the 9th week of her second pregnancy. On admission,
      computed tomography showed an abnormal mass lesion in the right frontal lobe, and
      a brain tumor was suspected. The patient and her family asked that that pregnancy
      be terminated. Seven days after a surgical abortion, methionine PET was
      performed. The scan showed high methionine uptake in the pituitary gland as well
      as in the right frontal lobe tumor. We suspected that another tumor was present
      in the pituitary gland. The right frontal tumor was partially resected, and
      pathologic examination of the resected specimen showed an astrocytoma (grade 2).
      After the operation, the patient received 50 Gy irradiation and chemotherapy. Two
      months after the operation, we performed a second methionine PET scan, which
      showed high uptake in the residual right frontal tumor but not in the pituitary
      gland. Results of other radiologic studies of the pituitary gland were normal.
      These findings suggest that the transport of 11C methionine into the pituitary
      gland may increase during pregnancy. Moreover, the pituitary gland of pregnancy
      should be a part of the differential diagnosis of pituitary adenomas in PET
      scanning. The change in physiologic uptake by the female pituitary gland should
      be taken into account in the diagnosis of pituitary adenoma with methionine PET.

PMID- 9656255
TI  - [A case of hypertrophic cranial pachymeningitis associated with intramedullary
      lesion developed seizure marching from right lower extremity].
AB  - A case of hypertrophic cranial pachymeningitis associated with intramedullary
      lesion was reported. A 57-year-old male presented with the symptoms of Jacksonian
      seizure and weakness of right lower extremity. Neurological examination showed
      weakness and muscular atrophy of right lower extremity (MMT 1-2) and
      hyperreflexia. Superficial sensation and position sense were normal, however
      cortical sensory disturbance was recognized in his right lower extremity. MRI
      revealed diffuse dural thickening with gadolinium enhancement in the left
      convexity and hyperintense lesion in the bilateral (left dominant) frontal to
      parietal lobe on T2 weighted image. Magnetic resonance angiography (MRA) and
      digital subtraction angiography (DSA) showed occlusion of the superior sagittal
      sinus. Histological examination revealed extensive fibrous tissue with
      lymphocytes infiltration around the vessels. The cause of the intramedullary
      lesion in this patient may have been related to the occlusion of superior
      sagittal sinus, due to thickening dura mater and influence of inflammation.

PMID- 9656256
TI  - Translation trouble.

PMID- 9656257
TI  - Kava: an herbal sedative.

PMID- 9656258
TI  - Pharmacologic management of depression in the elderly.
AB  - Depression, the most common geriatric psychiatric disorder, is a disabling mood
      disorder that impairs one's well-being and may even threaten a sufferer's life.
      Severely depressed elderly persons are more likely to kill themselves than
      individuals in any other age group. However, geriatric depression is, for the
      most part, a treatable and manageable illness. Antidepressant medication can be
      very effective in treating major depressive disorder (MDD). Because age-related
      physical changes in the elderly produce pharmacokinetics that are often different
      than that experienced by younger adults, different doses are often necessary.
      This article summarizes recommendations for selecting and initiating appropriate
      antidepressant therapy in elderly persons suffering from MDD. The benefits and
      drawbacks of tricyclic antidepressant agents, and other atypical antidepressant
      agents are discussed. Phases of treatment, drug selection, dosing, and
      educational tips for pharmacotherapy are presented.

PMID- 9656259
TI  - Focus groups reveal perils and promises of managed care for nurse practitioners.
AB  - Decades of practice and research suggest that nurse practitioners (NPs) provide
      cost-effective and high-quality care. Managed care's emphasis on prevention and
      cost savings led some policy makers to view NPs as a way to meet the need for
      primary care providers. However, access to and utilization of NPs has
      increasingly been controlled by managed care organizations (MCOs) through their
      selection of providers for primary care panels. This study employed qualitative
      methodology to examine NPs' experiences with MCOs. Three focus groups, comprising
      27 NPs in New York and Connecticut, revealed NPs' mixed reactions to managed care
      and a range of sentiments regarding NPs' efforts to be listed as primary care
      providers. The results reflected NPs' concerns about their perceived
      "invisibility," as well as their sense of "invincibility" in the ways in which
      NPs are responding to the barriers posed by MCOs. They identified barriers to, as
      well as ways to facilitate, being listed by MCOs, and described the importance of
      NPs working individually and collectively in negotiating with MCOs.

PMID- 9656260
TI  - Diagnosis and management of gastroesophageal reflux in infants and children.
AB  - Use of histamine blockers, proton pump inhibitors, and prokinetic drugs, along
      with traditional antacids, has become standard therapy for gastroesophageal
      reflux (GER) in symptomatic adults. Response to this therapy is assessed to
      confirm the diagnosis of GER, and is often advocated as the best way to establish
      the causes and effects of the disease. It is well documented that reflux occurs
      throughout the life span. However, the incidence in children is difficult to
      estimate, requiring interpretation of behavior and symptoms in nonverbal and
      atypical presentations. Unfortunately, the diagnosis of GER in children is often
      made after the development of complications such as aspiration pneumonia,
      esophagitis, or ulcers. Early recognition and intervention by primary care
      providers is necessary to prevent such serious complications of untreated GER.
      This article presents the pathophysiology and clinical manifestations of GER.
      Diagnosis in children is discussed, and recommendations for empiric therapy,
      including conservative measures and drug therapies, are presented.

PMID- 9656261
TI  - Promoting breast-feeding by managing common lactation problems.
AB  - Breast milk is nutritionally and immunologically superior to any known
      substitute. Morbidity and mortality are lower in breast-fed infants and their
      mothers, resulting in better health and lower health care costs. Despite the
      overwhelming evidence of health benefits and consequent endorsements from
      professional groups, many health care providers do not actively promote breast
      feeding initiation. They may actually undermine breast-feeding duration by
      providing incorrect advice when problems develop. This article provides
      recommendations for promoting breast-feeding and discusses diagnosis and
      management options for common maternal lactation problems, including sore
      nipples, eczema, candidal infection, and mastitis.

PMID- 9656262
TI  - Primary care management of otitis externa.
AB  - Otitis externa (OE) is an acute, painful inflammatory condition of the external
      auditory canal that affects all age groups and accounts for about half of all
      patients presenting with ear pain. Common causes are gram-negative bacteria,
      Staphylococcus aureus, fungi, and dermatologic conditions such as eczema,
      seborrhea, and psoriasis. Risk increases with prolonged exposure to heat and
      moisture, especially in those who swim frequently or live in a tropical climate.
      Treatment involves cleaning the canal thoroughly and instilling ototopical broad
      spectrum antibiotics. Although OE is relatively benign and easy to treat in the
      primary care setting, it can have life-threatening complications, especially in
      diabetic and immunocompromised patients. This article reviews the differential
      diagnosis, outlines treatment, and discusses preventive measures. A patient
      education sheet is provided.

PMID- 9656263
TI  - Common oral manifestations seen in patients with HIV/AIDS.

PMID- 9656264
TI  - Effects of the Five-step Strategy with videotape modeling on performance of the
      tennis serve.
AB  - This study was designed to compare two methods of instructing Singer's Five-step
      Strategy and their effect on the learning and performance of a tennis serve. 63
      university students classified as recreational tennis players were stratified by
      sex and then randomly assigned to one of three groups: Five-step Strategy with
      videotaped modeling, audiotape Five-step Strategy plus written transcript, or no
      strategy. Players performed seven blocks of 10 service attempts per block of
      serves. Points accumulated with each service attempt as well as the number of
      errors were the dependent measures. Separate 2-way analyses of variance were
      conducted for each phase of the study. No significant pretreatment differences
      were noted among groups. Further, all groups improved significantly across time
      on both dependent measures and maintained this improved performance on a
      subsequent retention test.

PMID- 9656265
TI  - Golf clubs: hidden home hazard for children.
AB  - Different accident patterns for golf equipment were noted for adults and
      children. Children are more likely than adults to be hit by a golf club as
      bystanders who entered the swing zone of a golf club. Previous publications
      investigating accidents involving golf clubs and over 2000 incidents involving
      emergency room treatment of children injured by golf clubs were reviewed. Most
      injuries occurred when unsupervised children played with golf clubs at home. When
      studies limit their focus to accident victims, who are currently being treated in
      the emergency room, hospital, or outpatient facility, no deaths are reported. A
      separate analysis of death certificates of children between the ages of 4 and 14
      years also identified death as a possible consequence as 19 deaths have been
      reported to the National Injury Information Clearinghouse. Based on these three
      sources of data, golf clubs should not be used by children unsupervised given the
      potential for serious and permanent head injury and death. Recommendations for
      parents and manufactures regarding the safety of golf clubs are provided.

PMID- 9656266
TI  - Relation between electrodermal- and visual-orienting responses and processing
      resource allocation.

PMID- 9656267
TI  - Competing personal goals and exercise behaviour.
AB  - Research on the determinants of exercise behaviour has not assessed the role of
      personal goals which may be in conflict with exercising. A cross-sectional study
      showed that 312 nonexercisers, 466 people who exercised once or twice a week, and
      202 people who exercised at the norm of at least three times a week differed
      significantly with respect to the number of important personal goals expected to
      be hampered by exercising at the norm. To be specific, the number of competing
      activities in the home was higher for the sedentary group than for those who
      exercised. Further, those who exercised at the norm reported fewer competing
      social activities than all other subjects and fewer competing self-developmental
      activities than the non-exercisers. Scores on the scale for activities outside
      the home did not differ significantly among the three groups. It is argued that
      any theoretical model of exercise behaviour should take into account the
      influence of competing personal goals on the initiation and continuation of
      exercise during leisure time.

PMID- 9656268
TI  - Cognitive strategies and recall of pace by long-distance runners.
AB  - The purpose of this study was to examine whether long-distance runners with high
      or low performance of recalling running pace differed in their use of cognitive
      strategies in a race. Recalling pace means the accuracy which runners have to
      approach their self-set target pace in a race. 60 male competitive runners who
      participated in a 20-km intercollegiate race were categorized as either runners
      with high recall of pace (accurate) or the runners with low recall of pace
      (inaccurate) on the basis of the discrepancy between a self-set target time and
      actual time. Analysis showed that the 30 accurate recallers used the attention
      strategies more frequently for recalling running pace, used the strategy of
      following other runners less frequently, and set a more appropriate finish time
      in accordance with their running ability than the 30 inaccurate recallers. The
      accurate recallers, who monitored their running pace and fatigue by using
      attention strategies, would reproduce more accurate self-set target times in
      accordance with their running ability.

PMID- 9656269
TI  - Cognitive, perceptual, and motor abilities in skilled basketball performance.
AB  - The differences among athletes of differing skill should assist successful
      identification and selection of the best athletes in a specific sport. For the
      purpose of this study, a laboratory study was conducted with a group of 13 men on
      the elite male national team of basketball players, 22 to 23 years of age, and a
      control group of 15 men of equal age (physical education class) to assess
      differences in their scores on cognitive skills (memory-retention, memory
      grouping analytic ability), perceptual skills (speed of perception, prediction,
      selective attention, response selection), and motor skills (dynamic balance,
      whole body coordination, wrist-finger dexterity, rhythmic ability). Analysis
      showed that elite male basketball players scored higher on hand coordination and
      lower on dynamic balance given their anthropometric measurements. Elite players
      were better on memory-retention, selective attention, and on prediction measures
      than the control group. The above skills are important in basketball performance.
      Researchers may examine whether other factors contribute more in the development
      of perceptual and cognitive skills.

PMID- 9656270
TI  - Auditory processing skills and hearing aid satisfaction in a sample of older
      adults.
AB  - The present study investigated the relationship between central auditory
      processing skills and satisfaction with hearing aids in a hearing-impaired
      geriatric sample of 58 adult wearers of hearing aids who were between the ages of
      65 and 91 years. Analysis suggests the importance of adding central auditory
      tasks such as compressed speech or dichotic listening tasks to the evaluation of
      candidacy for hearing aids. This could lead to the better understanding of
      satisfaction with amplification by the geriatric population.

PMID- 9656271
TI  - Internal consistency of scores on Matching Familiar Figures Test-20 and
      correlation of scores with age.
AB  - Internal consistency of scores on the Matching Familiar Figures Test-20 and
      patterns of latencies and errors were estimated for 337 boys and 287 girls
      between the ages of 6 and 11 years, in the first five grades of primary school.
      The Matching Familiar Figures Test-20 presented moderate coefficients of internal
      consistency (.77) for errors and high coefficients (.94) for latencies. The
      correlation between latencies and errors was moderate and significant (-.50).

PMID- 9656272
TI  - Effects of magnetic stimulation through VLF-sferics on reaction time.

PMID- 9656273
TI  - Effects of conditioning on physical fitness and club head speed in mature
      golfers.
AB  - The purpose of this study was to evaluate the effects of an 8-wk. conditioning
      program on selected measures of physical fitness and golf performance for 12 male
      and 5 female recreational golfers (M age = 52.4 yr., SD = 6.7 yr.). Measurements
      were made at baseline and following the intervention. The twice-per-week program
      consisted of strength training, flexibility, and plyometric exercises. Analysis
      of the pre- and posttest scores showed that conditioning was associated with
      significant increases in muscular strength, flexibility, and club head speed.
      Without a control group, the data suggest conditioning may be a worthwhile
      activity for mature golfers.

PMID- 9656274
TI  - Sex, sport, situation, and competitive state anxiety.
AB  - Within a multivariate design, the relationship between sex, sport, and
      competitive situation with state anxiety was examined. The Competitive State
      Anxiety Inventory-2 was administered to selected intramural basketball and
      volleyball teams (ns = 266 and 226) prior to round-robin and play-off
      competition. Multivariate analysis of variance yielded a significant interaction
      of sport by sex and a significant main effect for sport. Follow-up tests
      indicated that basketball players scored higher somatic and cognitive state
      anxiety than volleyball players. Women scored higher on somatic and cognitive
      state anxiety than men prior to play-off games. Results are discussed in terms of
      importance of a multivariate approach to studying competitive anxiety.

PMID- 9656275
TI  - Clothing preferences of older consumers.
AB  - The study focused on identifying the apparel needs of older men and women in a
      midwestern county. A survey technique was used to collect data on older peoples'
      preferences for apparel including accessories, most preferred items, identified
      similarity with previous apparel choices, and identification of buyer of the
      apparel. Descriptive statistics were used to analyze the data. Implications of
      the findings for future research and possibility of use by apparel designers,
      manufacturers, and retailers are discussed.

PMID- 9656276
TI  - Variation among nonclinical subjects on a line-bisection task.
AB  - Absence of leftward bias in a line-bisection task is often used as a clinical
      hemispheric indicator, but the effect is not uniform in a normal population. Sex,
      handedness, and strategy variables affect the strength and direction of any bias.

PMID- 9656277
TI  - Key components of the Mozart effect.
AB  - The results of studies intended to replicate the enhancement of spatial-temporal
      reasoning following exposure to 10 min. of Mozart's Sonata for Two Pianos in D
      Major (K.448) have been varied. While some studies have replicated the effect,
      others have not. We suggest that researchers' diverse choice of dependent
      measures may account for these varied results. This paper provides a
      neurophysiological context for the enhancement and considers theoretical and
      experimental factors, including the choice of dependent measures, the
      presentation order of the conditions, the selection of the musical composition,
      and the inclusion of a distractor task, that may contribute to the various
      findings. More work is needed before practical applications can be derived.

PMID- 9656278
TI  - Body-type stereotyping in therapeutic judgments.
AB  - 23 professional psychotherapists and 25 graduate student trainees rated line
      drawings of three clients' body types on 21 clinically relevant personal
      characteristics. Professionals and students alike rated ectomorphic and
      endomorphic clients less favorably than mesomorphic clients.

PMID- 9656279
TI  - Stimulus-response compatibility and position of the hands: nonadditive effects.
AB  - An experiment was conducted using a two-choice stimulus-response compatibility
      task factorially combined with position of the hands. Subjects responded to a
      visual target word (Left or Right) by pressing on the left or the right key
      depending on the compatible or incompatible assignment and performed the task
      with the hands uncrossed or crossed. The effects of Stimulus-response
      compatibility and Position of hands were not additive. Moreover, no effect of
      compatibility occurred in the crossed-hand condition. These findings are
      consistent with the predictions derived from a recent hypothesis assuming that in
      some particular experimental conditions the presentation of the stimulus will
      activate two automatic responses. The two stimulus-response compatibility
      mappings related to these two automatic responses have been shown to be
      positively or negatively correlated depending on the factorial combination of
      Stimulus-Response Compatibility and Position of Hands. As a consequence the
      effects of the two factors theoretically cannot be additive. This assumption
      accounts for the present results.

PMID- 9656280
TI  - Hallucinations.
AB  - Hallucinations, sensory perceptions without environmental stimuli, occur as
      simple experiences of auditory, gustatory, olfactory, tactile, or visual
      phenomena as well as mixed- or complex experiences of more than one simple
      phenomenon. The nature of the hallucination assists localization, differential
      diagnosis, and treatment planning. In particular, the presence of persistent
      visual hallucinations of persons with Parkinson's disease predicts dementia,
      rapid deterioration, permanent nursing home placement, and death. Hallucinations
      in persons with Alzheimer's disease are often associated with serious behavioral
      problems and predict a rapid cognitive decline. Theories of the etiology of
      hallucinations include (1) stimulation, e.g., neurochemical, electrical, seizure,
      and ephaptic, and (2) inhibition, e.g., destruction of normally inhibitory
      functions, resulting in disinhibition as in the Charles Bonnet and phantom limb
      syndromes. Functional neuroimaging procedures suggest anatomical associations for
      hallucinations. While hallucinations may be a symptom of medical, neurologic, and
      psychiatric disorders, they may also occur in a wide range of human experiences.

PMID- 9656281
TI  - Tobacco use and sport fandom.

PMID- 9656282
TI  - Fatal alcohol-related traffic crashes increase subsequent to changes to and from
      daylight savings time.
AB  - On the hypothesis that sleepiness and alcohol interact to increase the risk of
      alcohol-related traffic fatalities, the percentages of alcohol-related fatal
      traffic crashes were assessed for the entire state of New Mexico for the years
      1989-1992, for each of the seven days that preceded the changes to and from
      Daylight Savings Time and for each of the 14 days which followed the changes to
      and from Daylight Savings Time. Consistent with our hypothesis the percentage of
      alcohol-related fatal crashes increased significantly during the first seven days
      after these changes in Daylight Savings Time.

PMID- 9656283
TI  - Feeding method and motor activity in 3-month-old human infants.
AB  - It is currently acknowledged that breast-fed and formula-fed infants exhibit
      different rates of physical growth. Little is known, however, about behavioral
      differences that may be attributable to early feeding method. In the present
      investigation, activity level in 3-mo.-old infants was examined by measuring
      motoric output in 40 breast-fed and 40 formula-fed infants. Maternal ratings of
      temperament did not differ across the two groups, but scores derived from the
      actometer in a laboratory setting showed breast-fed infants to be more active.
      Upper limb activity appeared to be particularly sensitive to feeding regimen.
      Possible explanations for this effect as well as implications of these results
      are discussed.

PMID- 9656284
TI  - Additional developments regarding manifest dream structure and function.
AB  - Detailed observation of manifest dream sequences indicated self-advocating
      occurrences facilitating the dreamer's self interests, opposed by self
      adversarial interferences. Further examination of manifest dream syntactical
      structure additionally suggested a recurrent, four-step, algorithm for personal
      problem-solving within an interpersonal matrix consisting of the following cycle:
      (1) an opening scene setting the stage, (2) for the emergence of a self-concern,
      (3) which evokes a strategy to deal with dreamer's self-concern, (4) that
      eventuates in a consequence of the strategy. These steps repeat until the dream
      ends. Observing these manifest dream structural features, attributable to
      broadening past theorizing with "bottom-up" approaches, clarifies the dream's
      problem-solving process by providing an empirical, observable framework for dream
      interpretation and by contributing to their consensual validation.

PMID- 9656285
TI  - Differences in several perceptual abilities between experts and novices in
      basketball, volleyball and water-polo.
AB  - The aim of this study was to examine differences between experts and novices in a
      number of perceptual abilities. Three groups of elite athletes, 44 members of
      Greek national teams in basketball (n = 12), volleyball (n = 13), and water-polo
      (n = 19) were selected. Two groups of physical education students (ns = 18 and
      21) were novices. The measured abilities were selected as the most important for
      an elite athlete by expert coaches in the three sports. The four most frequently
      selected abilities for each sport, according to the coaches' opinions, were
      finally assessed. Analysis showed that differences were fewer than expected.
      Basketball experts were better on prediction and selective attention. Volleyball
      experts performed better on perceptual speed, focused attention, prediction, and
      estimation of speed and direction of a moving object. Water-polo players had
      significantly better scores than the novices on decision-making, visual reaction
      time, and spatial orientation. It seems that the nature of each sport strongly
      influences the way perceptual abilities differentiate elite athletes from
      novices.

PMID- 9656286
TI  - Effect sizes of mountains and molehills.
AB  - Decisions about environmental aesthetics require valid, understandable
      measurements of visual impacts. This study reports well known scientific
      measurements (standardized mean contrasts) for well known images (mountains and
      molehills). The scientific measurements of visual preferences for mountains and
      molehills were 1.17 and -0.05, respectively.

PMID- 9656287
TI  - Video-assisted cycling alters perception of effort and increases self-selected
      exercise intensity.
AB  - Two studies were conducted to assess whether indoor video-assisted cycling
      influenced a person's quality of exercise (subjectively and quantitatively),
      compared to indoor cycling alone. In the first study 12 recreationally active
      subjects completed an initial test of VO2max, and three randomized trials of
      cycling at 70% VO2max (35 min.) watching a commercial cycling tape (cycle video),
      a test pattern displayed on the ergometer screen (blank video), or no video.
      Subjects' ratings of perceived exertion (RPE) and Affect were recorded, and heart
      rate and oxygen consumption (VO2) were measured during testing. The second study
      required 12 different subjects first to complete an assessment of VO2max and then
      two randomized trials (cycle video and no video) on a cycle ergometer where they
      freely set the intensity of their own exercise. Measurements of VO2, heart rate,
      blood lactate, power output, RPE, and Affect were recorded during testing.
      Results of Exp. 1 indicated that subjects' perceived effort equally between the
      two conditions, yet reported significantly (p < .05) higher affect at 25 and 35
      min. of cycling during the cycle video condition than no video condition. Results
      of Exp. 2 indicated that despite similar levels of blood lactate, subjects
      exercised at a significantly higher intensity during the cycle video condition
      compared to no video condition, with a higher VO2 and heart rate. The data
      support the use of indoor exercise videos to improve the exercise experience and
      also to increase the physiological demands of indoor exercise.

PMID- 9656289
TI  - Subjective organisation in the recall of abstract body movements.
AB  - Subjective organisation is a well known characteristic of verbal free recall in
      that items are recalled in groupings known as "chunks" or "clusters." This
      organisation is indicative of a memory strategy and has been used to derive the
      cognitive structure of particular areas of knowledge. Clustering might also occur
      in the free recall of body movements. Subjects attempted to learn unfamiliar
      abstract body movements over five learning and recall trials. Analysis showed
      that subjective organisation occurred and increased with additional recall
      trials. This extends the clustering effect to the free recall of body movements.
      It is suggested that this effect can be used to probe the cognitive structure of
      motor memory.

PMID- 9656290
TI  - Bulimia and perceived voice disorders: a preliminary study.

PMID- 9656291
TI  - Implicit memory for odors: a possible method for observation.
AB  - In an experiment 143 subjects were instructed to assign odors to contexts which
      were displayed in a slide session. The slides depicted contexts from three areas
      of everyday life which partly contained visual cues related to a presented odor.
      After rating the fit of each odor to a context, the subjects rated the odors for
      pleasantness. Analysis showed a strong influence of the visual cue on the rating
      of fit for the contexts containing an odor-related visual element. In contexts
      without a visual cue, rating of fit showed an influence of implicitly learned
      memories of odor. The rating was not affected by the pleasantness of the odors.
      The 1995 work of Schab and Crowder is critically reviewed, and results are
      discussed within the framework of new, more ecologically oriented research on
      memory for odor.

PMID- 9656292
TI  - Some aspects of self-reported hand preference.
AB  - The aim of the present study was to compare self-reported handedness with the
      directly tested hand preference using a 10-item battery in sample of 1223
      students. The question assessing self-reported handedness was whether you are a
      left- or a right-hander or you use both hands equally. Responses indicate that
      self-reported handedness is a crude but possible method of measurement. Female
      right-handers showed the best agreement.

PMID- 9656294
TI  - Body mass indexes and historical ratings of U.S. presidents: 1948-1984.

PMID- 9656293
TI  - Fractionated premotor, motor, and ankle dorsiflexion reaction times in
      hemiplegia.
AB  - Ten hemiplegic subjects completed 20 rapid dorsiflexions of their afflicted and
      nonafflicted limbs. Electrodes were attached to the tibialis anterior and the
      gastrocnemius muscles and electromyograms were recorded for their premotor time,
      motor time, and simple reaction time during ankle dorsiflexion and plantar
      flexion of their lower limbs. The fractionated components of reaction time,
      namely, premotor time and motor time, of both legs were statistically compared.
      It was found that the premotor time of the subject's stroke-affected limb was
      significantly slower than the premotor time of the nonaffected limb (control),
      with no differences between their associated mean motor times. These results
      supported the hypothesis that a stroke has a deleterious affect upon the central,
      premotor time processing centers and has no disruptive influence upon the
      peripheral motor time. Comparing the fractionated components of reaction time
      (premotor time and motor time), with simple reaction time, the former provided a
      more sensitive and valid method to detect possible injurious side effects of a
      stroke upon the brain's neuromotor transmission centers and subcenters, and their
      peripheral, stimulus, response network.

PMID- 9656295
TI  - Influence of spatial mapping on manual aiming asymmetries.
AB  - Two experiments were conducted to examine manual asymmetries in a one-dimensional
      aiming task. In Exp. 1, 10 right-handed adults slid a computer mouse 13 cm on a
      graphics tablet with both the right and left hands to targets of 3 different
      diameters. Under these conditions, the movement time for the right hand was
      significantly faster as expected. In Exp. 2, subjects performed similar movements
      to move a cursor 13 cm on a computer monitor. Thus the study was identical except
      the stimulus-response mapping was indirect. In this situation, there were no
      significant difference for either movement time or movement error between hands
      despite these performance measures indicating the target aiming was more
      difficult in Exp. 2. Because increases in task difficulty generally result in a
      greater advantage for the right hand, as indicated by Todor & Smiley, 1985, the
      present studies suggest that superiority of the right hand in aiming tasks may be
      diminished when spatial translation is required. Perhaps the spatial translation
      requires greater involvement of the right hemisphere, a process associated with
      manual advantage for the left hand, previously suggested by Roy and MacKenzie.

PMID- 9656296
TI  - Benefits of providing cognitive performance strategies to novice performers
      learning a complex motor skill.
AB  - Verbal reports were collected from experienced performers during acquisition
      trials of a novel throwing task and summarized as cognitive performance
      strategies. These strategies were incorporated in the practice regimen of 8
      novices with no sport experience who learned the same task. A control group of 8
      novices practiced the task without the experts' cognitive performance strategies.
      The performance of the novices who used the strategies was similar to that of the
      experts and significantly better than the performance of the control novices.

PMID- 9656297
TI  - Patterns of adaptation to conflict in bulimia and temporo-mandibular joint
      disorder.
AB  - Two age- and education-matched groups of 45 women, respectively, with the
      diagnoses of Bulimia and of Temporo-mandibular Joint Disorder, were administered
      the Serial Color-Word Test, to assess differences in the pattern of adaptation to
      conflict (the latter being represented by the Stroop task). Three types of norms
      (clinical, nonclinical and based on reading times) and the functions derived from
      a previous cluster analysis were employed. Comparisons utilizing clinical norms
      and cluster analytical functions did not significantly differentiate between
      groups. According to both nonclinical norms and norms based on reading times, the
      two clinical groups were significantly different concerning the distribution of
      adaptation patterns. Bulimic patients resorted more often to the Dissociative
      pattern (high nonlinear change of reading times), while temporomandibular
      patients were characterized by the Cumulative pattern (high linear change) and,
      secondarily, by the Cumulative-Dissociative pattern (high linear and nonlinear
      change). Intergroup differences were more marked when employing the new norms
      based on reading times.

PMID- 9656298
TI  - Individual differences in the performance of highly learned skill.
AB  - Examination of individual differences (intertrial correlations) of highly skilled
      performance by professional golfers demonstrated that individuals respond to
      conditions in dissimilar ways, despite having strong central tendency. Behavioral
      scientists may benefit extraordinarily by heeding the advice of Cronbach and
      Jones to combine differential and experimental techniques.

PMID- 9656299
TI  - Assessment of memory in multiple sclerosis patients using the Memory Assessment
      Scale.
AB  - Previous assessment of memory function in multiple sclerosis patients has yielded
      mixed findings regarding the type and severity of memory deficits, which may be
      due to (1) differential selection of scales for memory assessment; (2) limited,
      inconsistent or weak reliability and validity data for the memory scales
      employed; (3) poor standardization techniques; (4) lack of theoretical foundation
      for the measure; and (5) limited control of confounding variables, e.g.,
      education, age and the use of nonverbal memory tests. The purpose of the present
      study was to assess memory function in multiple sclerosis subjects using the
      verbal subtests of the Memory Assessment Scale, a relatively new measure designed
      to overcome many of the aforementioned problems. Participants included 57
      patients diagnosed as relapsing-remitting, 47 diagnosed as chronic progressive
      (two generally recognized types of multiple sclerosis), and 132 control
      participants. A multivariate analysis controlling for age and verbal IQ was
      significant (Wilks = 5.64, p < .001). One way follow-up tests showed both groups
      with multiple sclerosis had significantly diminished performance across all
      memory variables when compared with controls, with the exception of List
      Clustering Acquisition. This indicated that the patients used clustering
      (mentally grouping similar words together) as often as controls did. These
      findings provide support for the presence of significant and consistent verbal
      memory impairment in multiple sclerosis patients and the particular importance of
      using psychometrically sound measures in the assessment of this population.

PMID- 9656300
TI  - An attempt to distinguish between two reversal processing strategies for learning
      modeled motor skill.
AB  - The first purpose was to examine the effects of reversal processing strategy of
      visual information on recognition and acquisition of a sequential gross movement
      task. The second purpose was to examine the relationship between a measure of
      reversal processing strategy and movements during eye fixation. 24 undergraduates
      were assigned into one of three conditions, a Reversal-emphasized condition in
      which subjects were instructed to recognize the movement correctly from a
      reversed angle, a Recognition-emphasized condition in which subjects were
      instructed to recognize the movement correctly, and a Recall-emphasized condition
      in which subjects were instructed to reproduce the movement correctly. Subjects
      observed stimuli with the model facing them. Following observation, the subjects'
      recognition of stimuli was tested with model facing towards (Facing Angle) and
      facing away (Rear Angle). Recall tests were carried out after the two recognition
      tests. Analysis indicated that accuracy and response time on recognition tests
      improved under each condition, but there were no other effects. The Reversal
      emphasized condition showed significantly greater modeling effect than the other
      conditions. Movements during eye fixation were very similar among conditions.

PMID- 9656301
TI  - Comparing spatial abilities of collegiate athletes in different sports.
AB  - Researchers indicated that androgen enhances spatial ability in women but
      inhibits it in men. Since studies also indicate that athletes have higher than
      normal levels of androgen, whether spatial perception scores differed for men and
      women in different sports was examined. Spatial tests (visualization and
      orientation) were given to 150 men and 150 women collegiate athletes in different
      varsity sports. Analysis showed the women scored significantly higher than the
      men. In basketball, a sport common to both sexes, women did significantly better
      but this was not found in the other mixed-sex sports (baseball, swimming, and
      track).

PMID- 9656302
TI  - Interference as measured by the Stroop Color-Word Test and the Direction-Word
      Test with varied comparison stimuli.
AB  - The current investigation explored the influence of irrelevant stimuli on the
      standard Stroop color-word effect. Also investigated is the effectiveness of a
      new direction-related test which, unlike previous direction-related Stroop-like
      measures, exactly parallels format of the original Stroop in administration. This
      Direction-Word Test uses arrowheads at the ends of each target word to depict
      direction, e.g., left, right, and middle. 92 undergraduate students volunteered
      to participate. Analysis indicated that interference is found on the Color-Word
      Test, even with noncolor words as stimuli. Interference also occurred on the new
      Direction-Word Test. The correlation between the two forms of the Stroop effect
      was low, although significant, perhaps indicating there are different systems
      involved in response interference.

PMID- 9656303
TI  - Public school speech-language pathologists' knowledge of sickle cell disease.

PMID- 9656304
TI  - Combined effects of goal setting and performance feedback on performance and
      physiological response on a maximum effort task.
AB  - A laboratory experiment was conducted (N = 40 subjects) to examine whether goal
      setting would be associated with reduced heart rate on an endurance task.
      Participants performed an endurance task on an ergometer bicycle. One week later
      when participants performed the task again half of them set a specific personal
      goal for an increase in performance. Analysis indicated that subjects who set a
      goal showed significant improvement in comparison with the control group.
      Moreover, subjects in the goal group had a significantly lower mean heart rate
      during the test and had a higher mean heart rate at the end of the test than on
      the first trial. Results are discussed in terms of combining cognitive and
      physiological explanations for the beneficial effects of goal setting on
      performance.

PMID- 9656305
TI  - Role of auditory temporal processing for reading and spelling disability.
AB  - The role of auditory temporal processing in reading and spelling was investigated
      in a sample of 30 children and one of 31 adults, using a gap-detection task with
      nonspeech stimuli. There was no evidence for a relationship between reading and
      spelling disability (dyslexia) and the gap-detection threshold. The results were
      discussed regarding the relevance for the popular hypothesis of an auditory
      temporal processing deficit underlying dyslexia.

PMID- 9656306
TI  - Emotion and style in 30-second television advertisements targeted at men, women,
      boys, and girls.
AB  - A program for objective textual analysis which incorporated measures of style,
      word emotionality, and word imagery, was used to score the verbal portion of 152
      30-sec. television advertisements. This analysis indicated that advertisements
      directed at children were more active, longer, and less negative than those
      directed at adults. A comparison of advertisements directed at males and females
      regardless of age showed greater linguistic complexity (more words, fewer common
      words) when their text was directed at women and girls. Each of the 13 stylistic
      and emotional measures used to describe advertisements produced at least one
      significant difference associated with the age or the sex of the target
      population or their interaction.

PMID- 9656307
TI  - Some relationships among affection, aggression and alcohol abuse in the family
      setting.
AB  - Three questionnaire studies involving 101, 270, and 144 college students examined
      the relationship between affectionate behaviors and aggressive behaviors in the
      family environment as rated by the college students. Measures of affection and
      aggression were significantly negatively associated in nearly all analyses.
      Participants' ratings of parental alcohol abuse were positively associated with
      measures of parental aggression and negatively correlated with measures of
      parental affection.

PMID- 9656308
TI  - Seasonal variations in melatonin may modulate glycemic response to exercise.

PMID- 9656309
TI  - Replicated factor analysis of the Italian Version of the Body Image Avoidance
      Questionnaire.
AB  - A multisample factor analysis identified two different solutions, a 3-factor
      solution from the high school sample of 439 subjects and a 4-factor solution from
      both the university sample of 200 subjects and an obese sample of 142 subjects.
      However, in the first sample Factor 1 included the same items which formed Factor
      2 and Factor 4 in both the second and the third samples. This suggests that the
      structure of the questionnaire can be adequately described by four different
      factors. The analysis of the factor loading also indicated that six items should
      be removed (Items 2, 3, 10, 11, 17, 19) from the Italian version.

PMID- 9656310
TI  - Factor structure of the Italian version of the Body Satisfaction Scale: a
      multisample analysis.
AB  - The paper describes the factorial structure of the Italian version of the Body
      Satisfaction Scale, a simple self-report questionnaire designed to assess
      satisfaction with 16 body parts. The results suggest that the structure of the
      questionnaire can be adequately represented by three different factors. Even if
      this solution is different from the one obtained in the original English samples,
      this interpretation was confirmed by a cross-validation on 806 subjects, a
      clinical sample and two normal samples. This result may be useful for the
      screening of subjects at risk for eating-disorders because it makes possible
      prediction of targeted areas of dissatisfaction which is not generally possible
      with other inventories. The analysis of the factor loadings also suggested that
      three items should be removed (teeth, eyes, and ears) from the Italian version.

PMID- 9656311
TI  - Prenatal alcohol exposure and communication, behavior, and nonverbal intelligence
      of 3 school-age children.
AB  - Associations of prenatal alcohol exposure in speech, language, behavioral, and
      intellectual development were investigated in three school-aged children
      diagnosed with Fetal Alcohol Syndrome, accompanied by Attention Deficit
      Hyperactivity Disorder. Each child showed similar patterns of moderate-to-severe
      dysfunctional behavior; however, their scores on speech, language and nonverbal
      intellectual measures were highly variable.

PMID- 9656312
TI  - The physioacoustic method and the creative process.
AB  - This study investigated the physioacoustic chair's, i.e., an application of low
      frequency sound waves, possible psychological effects with respect to deductive
      thinking and creativity as well as its possible effect on heart rate. Subjects,
      21 men and 21 women, were randomly assigned in equal numbers to three groups: a
      control group, a placebo group, i.e., a group who believed that they underwent a
      physioacoustic treatment program which they however did not undergo, and a
      physioacoustic treatment group. After manipulation, subjects were required to
      take three psychological tests (measuring fluency and originality, preconscious
      thinking, and deductive thinking) in random order. During the entire experiment,
      subjects' heart rates were registered every minute. Analysis showed no
      significant differences among the groups with respect to psychological effects or
      to heart rate. The results were interpreted to mean that the physioacoustic chair
      provides a form of relaxation which does not produce effects on the creative
      process.

PMID- 9656313
TI  - Exercise dependence among competitive power lifters.
AB  - Scores on exercise dependence examined among a sample of 14 competitive power
      lifters showed higher exercise dependence among lifters than those previously
      reported for endurance athletes.

PMID- 9656314
TI  - Interferon beta 1-b in verbal memory functioning of patients with relapsing
      remitting multiple sclerosis.
AB  - The effects of interferon Beta 1-b (Betaseron) on verbal memory functioning was
      examined in 167 patients with relapsing-remitting multiple sclerosis and 112
      matched normal controls. Subjects were administered 10 verbal memory tests from
      the Memory Assessment Scales and the Verbal subtests from the Wechsler Adult
      Intelligence Scale. Analysis showed subjects treated with Betaseron (n = 73) did
      not perform significantly better on measures of verbal memory or verbal ability
      than subjects not receiving the drug (n = 94), although the mean performance of
      treated subjects was higher across all verbal memory tests. Both groups of
      patients performed significantly worse on verbal memory subtests measuring list
      acquisition, delayed list recall, delayed cued recall, and the immediate and
      delayed recall of names and faces than control subjects. Although patients had
      lower performance scores across all memory tests than the control subjects, their
      scores were not within the impaired range. These results do not permit a clear
      conclusion about the effects of Betaseron on verbal memory for any effect is
      probably obscured by the relatively preserved cognitive functioning of this
      outpatient sample.

PMID- 9656315
TI  - Connection between synchronization of oscillatory activities at early stages and
      a final stage in the visual system.
AB  - Singer's group and we found synchronized oscillatory responses at early stages
      and at a final stage in visual processing, respectively. However, the former
      occurs on a millisecond time scale and the latter on a second time scale. We have
      considered that this results from a difference in scale of something which takes
      part in the oscillations. From this viewpoint, here we first find suppression
      effects on both figure and ground of a pattern and on only the ground in a
      binocular-rivalry situation and then examine, using the effects of two steps,
      what oscillates and synchronizes at the last stage for form. Finally, we conclude
      that the synchronous neuronal oscillations depend on firing patterns of neurons
      at early stages in the visual system and the psychophysical ones on
      configurations of the spread effect of strength of pattern involved closely in
      whole processing of the visual system and the latter originates in the former.

PMID- 9656316
TI  - Licensure of adapted physical education teachers and undergraduates' attitudes
      toward students with disabilities.
AB  - This study compared attitudes of 816 undergraduates toward students with
      disabilities by whether the state licensed teachers for adapted physical
      education. Analysis indicated mean attitude scores in states with such licensure
      were significantly more positive than in states working toward licensure and
      those with none.

PMID- 9656317
TI  - Multiple streams of time consciousness: a new model of retrospective timing.
AB  - This note suggests a new hypothesis for retrospective timing, that, when one
      experiences a period of time in which plural contexts progress simultaneously, a
      stream of time consciousness is formed for each context and a temporal judgment
      to the period is made for each of the streams. In the experiment, 17 subjects
      observed an event in which plural contexts progressed simultaneously and
      estimated the time a certain thing occurred during the event. Subjects' estimated
      times varied with the number of changes in the context which the subjects were
      required to judge. The hypothesis was supported.

PMID- 9656318
TI  - Gene-environment interactions in the pathogenesis of type 2 diabetes mellitus:
      lessons learned from the Pima Indians.
AB  - The comprehensive longitudinal studies of diabetes conducted in the Pima Indians
      of Arizona over the last 30 years indicate that both genetic and environmental
      factors play a critical role in the pathogenesis of the disease. Pre- and
      postnatal exposures as well as diet and physical activity in adulthood markedly
      affect risk of developing NIDDM in this population. In addition, the high
      prevalence of diabetes in the Pimas relative to other populations and the
      familiality of the disease and its precursors, strongly suggest a substantial
      genetic basis. Interactions between genes and the environment are obviously
      important in the pathogenesis of NIDDM, but it remains unclear exactly how these
      interactions occur and how to adequately account for these effects when searching
      for genes contributing to diabetes. The realization that gene-environment
      interactions are significant, and may be the dominant mechanism increasing
      susceptibility to NIDDM, should encourage further investigations. Future progress
      in studying the genetics of NIDDM and other complex diseases will come not only
      from technical advances currently in development, but also from advances in
      understanding the pathophysiology of the disease and the role of gene-environment
      interactions, and a renewed emphasis on careful clinical characterization of
      subjects participating in these studies.

PMID- 9656319
TI  - Diet and cancer prevention: the concerted action polyp prevention (CAPP) studies.

PMID- 9656320
TI  - Genetics, calcium intake and osteoporosis.
AB  - Genetic factors explain a high proportion of the age-specific differences in bone
      density, size and turnover. The potential for interaction between hormonal, diet
      and lifestyle factors is likely to be important. Common allelic variation in the
      VDR is an example of normal gene variants altering Ca homoeostasis, with effects
      on body and bone size as well as bone density. The VDR findings suggesting
      interactions between genetic and nutritional factors are an important target for
      future research. These studies are complicated by the potential for effects of
      gene-gene interactions and of undefined environmental factors. These problems
      notwithstanding, considerations of environmental and nutritional contributions,
      such as Ca intake and vitamin D status, will be critical in interpreting these
      genetic pathways and in 'personalizing' nutritional recommendations.

PMID- 9656321
TI  - Nutritional and hormonal regulation of hair follicle growth and development.

PMID- 9656322
TI  - Nutritional and hormonal control of skeletal-muscle cell growth and
      differentiation.

PMID- 9656323
TI  - Nutrient regulation of intestinal proliferation and apoptosis.

PMID- 9656324
TI  - Some aspects of the metabolic response to surgical trauma.

PMID- 9656325
TI  - The role of nutrition and diet in rheumatoid arthritis.
AB  - Given the lack of understanding of the nutritional requirements in RA, plus the
      variability in its clinical course, it is difficult to produce specific dietary
      recommendations for RA. In general, sufferers should consume as varied a diet as
      possible, based on current Department of Health (1991) guidelines. Dietary
      counselling is important to help patients achieve this. Self-imposed elimination
      diets should be avoided and suspected food intolerance tested under strict
      clinical supervision. Nutrient megadosing is inadvisable, although dietary
      supplementation with Ca, vitamin D, folic acid or multivitamins and minerals
      should be recommended where necessary.

PMID- 9656326
TI  - The effect of prenatal diet and glucocorticoids on growth and systolic blood
      pressure in the rat.

PMID- 9656327
TI  - Nutrition, immunity and the fetal and infant origins of disease hypothesis in
      developing countries.

PMID- 9656328
TI  - Molecular biological approaches to nutrient-gene interactions.

PMID- 9656329
TI  - Response of placental amino acid transport to gestational age and intrauterine
      growth retardation.

PMID- 9656330
TI  - Regulation of liver gene expression by glucose.

PMID- 9656331
TI  - Modulation of immune function by dietary fatty acids.

PMID- 9656332
TI  - Post-translational events in the intracellular transit of apolipoprotein-B:
      modulation by dietary lipids.

PMID- 9656333
TI  - Antioxidant micronutrients and gene expression.

PMID- 9656334
TI  - A role of zinc in the regulation of gene expression.
AB  - Zn, without question, has important functions related to gene expression. Newer
      technologies applied to address these functions are providing answers relating to
      the importance of this micronutrient in human and animal health.

PMID- 9656335
TI  - Measuring food intake in farm and laboratory animals.

PMID- 9656336
TI  - Measuring food intake in wild animals: primates.

PMID- 9656337
TI  - Measuring intake in free-living human subjects: a question of bias.

PMID- 9656338
TI  - The role of technology transfer in parasite control in developing countries.

PMID- 9656339
TI  - Current status of food-borne parasitic zoonoses in South Africa and Namibia.
AB  - Epidemiological data on food-borne parasitic zoonoses in countries of southern
      Africa are sporadic. In a study of toxoplasmosis in South Africa, there was an
      overall prevalence of 21% (2, 147/10,228). Prevalences vary between the different
      cultural groups and from one geographical region to another. The prevalence rate
      for the San (Bushmen) people of Namibia and Botswana was 9% (65/725) compared to
      the 30% (190/635) found in the Indian and Black communities of Kwazulu-Natal
      province, South Africa. These variations are probably linked to the dietary
      habits of the different cultural communities. Cysticercosis appears to be most
      prevalent in the Eastern Cape Province (former Transkei), where pigs roam freely
      and sanitation facilities are inadequate or non-existent. Segments of tapeworms
      often feature as an ingredient of concoctions prepared by traditional healers and
      are suspected sources of many of the cases of cysticercosis in South Africa.
      Trichinella nelsoni has been identified in wild game in South Africa: so far no
      cases of infection in humans have been recorded. Cases of Sarcocystis have been
      identified in some instances but infection is probably underdiagnosed in the
      country.

PMID- 9656340
TI  - Current status of gnathostomiasis dorolesi in Miyazaki Prefecture, Japan.
AB  - Gnathostomiasis is an important food-borne parasitic zoonosis caused mainly by
      ingesting uncooked or undercooked flesh of freshwater fishes. Although four
      distinct species of the genus Gnathostoma were identified as the causative agents
      for human gnathostomiasis, human infections with G. doloresi have been found only
      in Japan, concentrated in Miyazaki Prefecture. So far we have found 25 cases in
      Miyazaki Prefecture. Although most of these patients were of cutaneous
      gnathostomiasis, two patients presented to the hospital with unusual clinical
      manifestations; one case was a pulmonary gnathostomiasis diagnosed by
      immunoserological methods, and the other was an ileus caused by migration of the
      late 3rd stage larva in the colonic tissue, which was found by post-operative
      histopathological examination. Although cutaneous lesions such as creeping
      eruption or mobile erythema are the common clinical features of gnathostomiasis,
      caution should be paid to the presence of such unusual cases.

PMID- 9656341
TI  - Trichinella in arctic, subarctic and temperate regions: Greenland, the
      Scandinavian countries and the Baltic States.
AB  - The transmission and occurrence of Trichinella spp according to the zoogeography
      of different climatic conditions, socioeconomy and human activity are discussed.
      Comparing arctic, subarctic and temperate regions, it appears that the species of
      Trichinella present, the composition of the fauna and the human activity are all
      very important interacting factors affecting epidemiology. In Greenland, where
      only sylvatic trichinellosis is present, the high prevalence in wildlife appears
      closely connected with polar bear hunting. In the Scandinavian countries, the
      prevalence of both sylvatic and domestic trichinellosis differ widely. Denmark is
      regarded as Trichinella-free in the case of domestic trichinellosis and sylvatic
      trichinellosis is very rare. In Sweden and Norway, Trichinella is found in
      wildlife but domestic trichinellosis is rare. In Finland, both domestic and
      sylvatic trichinellosis have increased dramatically during the last decade. Among
      the Scandinavian countries, Finland also has the largest populations of
      carnivorous mammals. In the Baltic states, Trichinella is frequently found in
      wildlife and domestic trichinellosis is increasingly diagnosed. The high
      prevalence in the widespread wildlife populations may have epidemiological
      importance in relation to the recent changes in production and infrastructure in
      these former Soviet states.

PMID- 9656342
TI  - Tapeworm infection resulting from pork eaten at a wedding banquet.
AB  - Forty-five people who had attended a wedding banquet were examined by means of
      both Avidin-Biotin Peroxidase Complex-ELISA (ABC-ELISA) and Kato stool thick
      smear technic. The results revealed that the positive rates with ABC-ELISA were
      15.56% (7/45) and Kato Katz 0.62% (1/161). There was a significant difference
      between the two positive rates (p < 0.005). Six people at the wedding had
      taeniasis and 4 of them also had cysticercosis. Local people have no habit of
      eating uncooked pork, but at this banquet the meat from an infected cysticerci
      pig was used for preparing dishes for the wedding feast and the cold dishes were
      contaminated by the bladder worms as the result of using the same chopping block.

PMID- 9656343
TI  - A survey report--July 1993: cysticercosis in the Grand Dani Valley, Jayawijaya
      District, Irian Jaya Province, Indonesia.
AB  - A community survey was conducted in Gran Dani Valley, Jayawijaya District, Irian
      Jaya Province, Indonesia. A total of 537 adults were asked whether they
      experienced epilepsy, and were physically examined for cysticercosis cysts. Forty
      eight percent experienced at least one attack of epilepsy. Men had attacks 2.5
      times more often than woman. Cysticercosis cysts were found in 26.5% men having
      4.6 times more cysts than women. The cysts were mostly found in the pectoral
      region. The survey showed a raise cysticercosis in the Highlands of Irian Jaya
      and is considered a public health problem. Treatment was not available, but
      improvement of personal and environmental hygiene would be important. Mass de
      worming activity should be a part of routine public health service in the
      district.

PMID- 9656344
TI  - Epidemiology of echinococcosis in Nepal.
AB  - Echinococcosis and hydatidosis is a parasitic zoonotic disease of human and
      animals. This disease has created public health and environment problems in all
      urban areas of Nepal. Based on the three year study (1993-1995) it has been
      revealed that the epidemiological cycle (indigenous) of Echinococcus granulosus
      parasite is dog-pig-dog cycle and human acquire infection accidentally through
      infected dog stool. However, this study has proved also the epidemiological cycle
      like dog-sheep-dog, dog-goat-dog and dog-buffalo-dog. This study was supported by
      International Development Research Centre (IDRC), Ottawa, Canada.

PMID- 9656345
TI  - Epidemiology of paragonimiasis in Korea.
AB  - In Korea, soybean-sauce soaked freshwater crabs (kejang) have been a favorite
      delicacy when eating a bowl of rice. This traditional food has been a main source
      of human paragonimiasis. Until the late 1960s, human paragonimiasis had been
      prevalent; at least two million people had contracted the infection as determined
      by intradermal tests. About 40% of these were egg positive. In the turmoil of the
      green revolution and industrialization in the 1970s/1980s, ecological damage
      occurred widely. In many streams, populations of snail and crustacean hosts were
      reduced to levels almost of extinction. Population reduction of the intermediate
      hosts was followed by lowered endemicity. Attitudes of people, changed during the
      period, also reduced chances of paragonimiasis. Survey data in the 1990s
      indicated that prevalence of human paragonimiasis has lowered to about one 100th
      of that in the early 1970s. In a referral system, however, about one hundred
      clinical cases have been diagnosed annually by antibody test (ELISA), undertaken
      for clinical differentiation from tuberculosis. At least 10% of freshwater crabs
      sold in local markets are infected with the metacercariae. Paragonimiasis control
      has benefited in Korea mainly by the untoward effects of water pollution. To
      place P. westermani infections as enzootic, health education and surveillance
      systems should have a priority.

PMID- 9656346
TI  - Pulmonary paragonimiasis and tuberculosis in Sorsogon, Philippines.
AB  - The clinical epidemiology of pulmonary paragonimiasis and tuberculosis was
      investigated in a known endemic municipality of Sorsogon, Philippines. Records of
      diagnosed tuberculosis patients on treatment and follow up at the local Rural
      Health Unit over a two year period from 1993 to 1994 were reviewed to provide an
      overview of pulmonary tuberculosis in the area, specifically to describe the
      population at risk, the basis for diagnosis and the proportion of case
      notification who were sputum negative. Patients from the same group of
      individuals as well as undiagnosed tuberculosis patients with productive cough,
      fever with chest and/or back pain, or hemoptysis were examined to look into
      clinical manifestations, duration of symptoms, history of crab-eating and sputum
      examination results for acid-fast bacilli and Paragonimus. There was difficulty
      in determining the number of non-responders as the records did not have any
      provision for the recording of such. Annual tuberculosis case notification rates
      for the two years (374 and 401 per 100,000 population) were higher than the
      national figure in 1991 (325 per 100,000 population) indicating that tuberculosis
      is still a major health problem in the area and tuberculosis control efforts may
      have to be more aggressive to better contain the disease. Twenty-six out of 160
      individuals surveyed were sputum smear positive for Paragonimus. Paragonimiasis
      rates were not significantly different in the two groups (15.6% vs 16.9%,
      respectively) indicating that there is a need for routine sputum examination for
      Paragonimus which is not available at present. Only six patients surveyed were
      sputum smear positive for acid-fast bacilli. A high index of suspicion is
      necessary to diagnose paragonimiasis and to be able to differentiate it from
      tuberculosis. The diagnosis may be suggested by a patient's place of origin being
      a known endemic area, a long period of chronic cough and the habit of eating raw
      or insufficiently cooked crabs or crayfish. Laboratories in endemic areas should
      have the capacity to differentiate between the two infections by being able to
      provide the routine laboratory procedures necessary for definitive diagnosis and
      treatment.

PMID- 9656347
TI  - Paragonimiasis in Sin Ho District, Lai Chau Province, Viet Nam.
AB  - Forty-four cases of pulmonary paragonimiasis, two also with evidence of cerebral
      infection, were found in Sin Ho District in Northern Viet Nam. There were 30
      males and 14 females, 2-30 years of age. The diagnosis was made by sputum
      examination. Pet dogs and wild dogs in the area were also found infected and the
      people often eat roasted crabs.

PMID- 9656348
TI  - Epidemiology and control of clonorchiasis in Korea.

PMID- 9656349
TI  - Epidemiological survey on clonorchiasis sinensis in Yangxin County of Hubei
      Province of PR China.
AB  - An epidemiological survey of clonorchiasis was conducted at Panqiao township of
      Yangxin County of Hubei Province from June to November, 1993. The positive rate
      of cercaria in the body of intermediate hosts, Parafossarulus stratulus and
      Alocinma longicornis was 12.25% and 3.84% respectively. Positive rates of
      metacercariae in the bodies of Pseudonaphona parva was 48.15%, Ctenopharyngodon
      idellus 17.24% and Hypophthalmichthys nobilis 18.18%. Positive rate of eggs in
      the feces of cats was 36.36% and pigs 16.67%. It has been confirmed that there is
      a natural focus of clonorchiasis sinensis at Yangxin County of Hubei Province. A
      total population of 6,865 in 20 sites of 10 production brigades of Panqiao
      township was surveyed for infection with Clonorchis sinensis. The average
      infection rate in the local residents was 5.80%. Male had a higher infection rate
      than female. The infected persons were mainly peasants and school girls and boys.
      Most of the infected persons had light infections (I0) without a serious clinical
      manifestations.

PMID- 9656350
TI  - Epidemiological aspects of aquaculture in relation to fish borne trematodiasis in
      Malaysia.
AB  - Epidemiological studies have been conducted to determine the association between
      fish and disease. The fish were obtained from rivers, streams, ponds and lakes
      but few from aquaculture farms. While no defined studies have been carried out in
      Malaysia, baseline data show that fish obtained from aquaculture farms (mixed
      farming) contributed to cases of opisthorchiasis and clonorchiasis.

PMID- 9656351
TI  - Fish- and shellfish--borne trematode infections in Canada.
AB  - Food-borne trematode infections are endemic in various parts of the world,
      particularly Southeast Asia. Despite the high prevalence, morbidity and total
      costs of these infections, they remain poorly recognized by public health
      authorities and consumers. Factors such as poor sanitation and traditional
      methods of food preparation hasten the spread of food-borne trematode infections
      in endemic regions and must be carefully examined in order to develop effective
      control strategies. There is also a growing risk to consumers in non-endemic
      countries as a result of international trade. A considerable quantity of
      freshwater fish and shellfish is imported into Canada from endemic countries in
      Southeast Asia. Some of these products are imported fresh or processed in such a
      way that the infective metacercariae may not be destroyed. Further, current
      inspection procedures in Canada may not detect the presence of all parasites in
      imported fish products. Therefore, there may be a risk of infection if the fish
      or shellfish is consumed raw or lightly cooked. Many of the cases of infection in
      Canada involve recent immigrants from endemic regions who have become infected
      either before arriving or through the consumption of traditional or ethnic dishes
      prepared from imported products. International travel and the increasing
      availability and interest in ethnic foods also contribute to the risk of
      infection in all Canadians. In addition to these imported trematodes, a number of
      species are found in freshwater fishes and shellfish in North America and have
      also caused illness in humans. Although the prevalence of infection remains
      relatively low in Canada, the need for an increased general awareness of food
      borne trematode infections and their causes is indicated.

PMID- 9656352
TI  - Application of hazard analysis critical control point (HACCP) as a possible
      control measure for Opisthorchis viverrini infection in cultured carp (Puntius
      gonionotus).
AB  - Opisthorchiasis due to Opisthorchis viverrini and transmitted through infected
      freshwater cyprinoid fish (carps) affects more than 8 million people in Thailand,
      People's Democratic Republic of Lao, and Vietnam. The Hazard Analysis Critical
      Control Point (HACCP)-concept has been recommended by FAO and WHO to be included
      in programs to control foodborne trematode infections (FBT). HACCP is a
      multifactorial approach to control food hazards through surveillance of diseases,
      foods, and operations and education. This study describes the first attempt to
      apply HACCP to the prevention and control of Opisthorchis viverrini in pond
      culture carp (Puntius gonionotus). The experiment was designed and carried out by
      a multidisciplinary "HACCP team" including experts in the field of public health,
      parasitology, epidemiology, aquaculture, fisheries extension and fish inspection.
      The investigation was performed in two fish ponds in the District of Sun Pa Tong,
      Chiang Mai, Thailand. In the experimental pond, fish was cultured according to
      HACCP principles and compared with the control pond, which followed conventional
      aquaculture practices. Water supply to the pond, fish fry, fish feed and pond
      conditions during the growing period were identified as critical control points
      (CCPs). Hazards were identified and analyzed, as well as control measures,
      critical limits, monitoring procedures, corrective actions, and record keeping
      developed for each one of the above CCPs. Complete pond preparation, particularly
      aiming to eliminate contamination of pond water with O. viverrini eggs, fish
      infected with parasite meacercariae and the first intermediate host (Bithynia
      spp), was conducted. After the pond was filled with water, O. viverrini
      metacercaria-free fry were released into the pond. The preliminary results
      obtained indicate that HACCP-based principles applied to carp pond culture could
      be used as a strategy to prevent and control O. viverrini. Further studies should
      be undertaken aiming to confirm these preliminary results.

PMID- 9656353
TI  - Common culture practices for cyprinids in Asia.
AB  - Cyprinids are the largest group of cultured freshwater fish and thus the most
      important from the aspect of fish-borne parasitic zoonoses. The common practices
      employed in the culture of this group are described to provide background
      information which may be used in the formulation of strategies for the control of
      these zoonoses. Only the common carp is cultured in monoculture: all the rest of
      the carp species are usually cultured in polyculture systems incorporating
      several species. Polyculture of cyprinids may be carried out in ponds, cages or
      in free range culture in natural or man-made water bodies, Polyculture of
      cyprinids is often integrated with agriculture, such as livestock, poultry or
      crop farming, utilizing byproducts of the agriculture activity, especially
      manure, as a source of nutrient for the fish pond. If precautions are not taken,
      this practice may provide an avenue for the transmission of fish borne parasites
      to man.

PMID- 9656354
TI  - Microbiological status of live eel and processed fish products for export to
      Japan.
AB  - Live eels and processed fish products from Malaysia are routinely checked for
      microbial pathogens before export to Japan. The eels and water from the ponds are
      screened for Vibrio cholerae and Salmonella spp, whereas the processed fish
      products are tested for microbial contamination (aerobic plate count), coliforms,
      E. coil and Vibrio cholerae. Results showed that live eels and water samples were
      negative for Vibrio cholerae but Salmonella spp were isolated occasionally.
      Various types of processed fish products had counts below 1.0 x 10(5) whilst
      coliforms, E. coli and Vibrio cholerae were absent. Records available showed that
      procedures involved in the production and transportation of live eel, preparation
      and processing of fish products have resulted in relatively safe food products.

PMID- 9656355
TI  - Cancer genes and cholangiocarcinoma.
AB  - Genes involved in cancer development include oncogenes and tumor suppressor
      genes. Ras oncogene and mutations in p53 tumor suppressor gene are commonly found
      in many types of cancer. In Thai patients with cholangiocarcinoma ras oncogenes
      occur less frequently than in other ethnic groups and furthermore, p53 mutations
      also occur with lower incidence when compared with Japanese subjects. It is
      unclear at this time the basis for these differences.

PMID- 9656356
TI  - Place of surgery in opisthorchiasis associated cholangiocarcinoma.

PMID- 9656357
TI  - A brief update on the diagnosis of trichinellosis.
AB  - The latest immunological and molecular methods for the diagnosis of swine and
      human trichinellosis are briefly reviewed. The following topics are discussed in
      more detail: isolation of specific antigens by continuous elution-isoelectric
      focusing methods, production of recombinant antigens, nature of immunodominant
      antigens, potential use of heat shock proteins (HSPs) as diagnostic antigens,
      roles of specific IgE and circulating antigens (CA). The immunodominant antigens
      were found to be highly heat resistant. The specificity and sensitivity of
      colorimetric sandwich ELISA, microfluorescence (ELFA), enhanced chemiluminescence
      (ECIA) and dissociated enhanced lanthanide fluoroimmunoassay (DELFIA) in
      detecting CA were compared. The last method is the most sensitive, detecting as
      little as 1 ng of antigens/ml of serum. CA was detected as early as 7 days
      postinfection of mice. The serum from a patient suspected to have acute
      trichinellosis in Hong Kong was also tested positive for CA.

PMID- 9656358
TI  - Production specific antigens from Trichinella spiralis using a continuous elution
      method and isoelectric focusing.
AB  - Immunodominant antigens of 45-53 kDa (one band per fraction) were obtained from
      excretory/secretory (E/S) and somatic products of infective-larvae of Trichinella
      spiralis using a continuous-elution method. They were further resolved by
      isoelectric focusing into different isoforms (45 kDa: pI4.47, 5.09, 5.47 and
      5.86; 47 kDa: pI4.72 and 4.97; 53 kDa: pI4.86, 5.11, 5.44 and 5.78). In
      immunoblotting, the isoforms of pI 5.09, 5.86, 4.97, 5.44 and 5.78 did not cross
      react with antisera against Trichuris suis, Metastrongylus apri, Gnathostoma
      hispidum and Stephanurus dentatus. Hence, they have the potential to serve as
      specific antigens for the serodiagnosis of trichinellosis.

PMID- 9656359
TI  - Serological investigation on human trichinellosis spiralis in Hubei Province of
      PR China.
AB  - PVC-ELISA for detection of human trichinellosis and its value of field
      application was explored during 1988-1994. Sera of 56 cases of clinically
      confirmed trichinellosis were tested for serum Trichinella antibodies by way of
      PVC-ELISA, and the positive rate was 100%. When the sera of 80 cases of healthy
      persons from non-endemic areas were tested for trichinellosis, they were all
      negative. For the purpose of exploring the cross-reaction of PVC-ELISA used for
      detection of trichinellosis, sera from 144 cases of other parasitoses were
      tested. Among them, the sera of 80 cases of schistosomiasis japonica for
      trichinellosis were negative; 30 cases of paragonimiasis and 30 cases of
      clonorchiasis were also negative. Among sera of 4 cases of cysticercosis, there
      was only one positive. The results showed that PVC-ELISA for trichinellosis had a
      high sensitivity and specificity. For field application, a population of 800 from
      endemic areas were examined by PVC-ELISA, 85 (10.63%) were positive. The infected
      persons were mainly in Xiangfan region of Hubei Province. The percentage of the
      positive of trichinellosis in Xiangfan region was 64.71% (55/85). The positive
      rate of males and females was 13.41% (57/425) and 7.47% (28/375), respectively.
      There was a difference among the age groups, with the highest in those > or = 20
      years. The findings of this field investigation suggested that the infection rate
      of trichinellosis spiralis was high in this province, especially in the Xiangfan
      region; and that PVC-ELISA was suitable for field application. The emphasis of
      trichinellosis control and research of this province should be in the Xiangfan
      region.

PMID- 9656360
TI  - Molecular genetic variation in Echinococcus and Taenia: an update.
AB  - An update on our understanding of molecular variation in Echinococcus and Taenia
      is provided. Genetic variation within certain species of Echinococcus is now a
      well accepted phenomenon and a number of intraspecific variants or strains of E.
      granulosus, in particular, have been characterized hitherto using a range of
      procedures. Newly acquired molecular information has now been used in
      epidemiological studies with E. granulosus and in phylogenetic analysis of the
      genus Echinococcus. Similarly, DNA approaches have been applied for taxonomic
      characterization of the recently recognized Asian Taenia, a third form of human
      Taenia, which occurs in Southeast Asia, and which is distinguishable from, but
      closely related to, Taenia saginata.

PMID- 9656361
TI  - Serodiagnosis of alveolar echinococcosis: detection of antibody against EM18 in
      patients and rodents.
AB  - An international collaborative study on echinococcosis has been carried out for
      the establishment of a simple means for differential serodiagnosis of alveolar
      echinococcosis (AE) from other parasitic diseases including cystic echinococcosis
      (CE). The main candidate epitope is Em18 (previously undescribed epitope of a low
      molecular weight protein of 18.5 kDa). Evaluation of the usefulness of Em18 is
      introduced in this review paper. Serum samples showing antibody response against
      Em18 are exclusively from AE. The predominant IgG subclass recognizing Em18 is
      IgG4 or IgG1 or IgG4 + IgG1 but never IgG2. There are good correlations between
      (1) the antibody response against Em18 and the presence of active lesions and (2)
      the antibody response against Em18 and the Em2-ELISA values. Em18 is, therefore,
      expected to be reasonably reliable and useful for differentiation of active AE
      from inactive AE. A new ELISA system using a partially purified Em18 enriched
      fraction (PP-Em 18/16-ELISA) has been evaluated for serodiagnosis of AE compared
      with Em2plus-ELISA. A total of 194 serum samples were examined: 127 sera from AE
      (79) and CE (48) in China where both AE and CE are endemic, 21 sera from CE in
      Australia where CE only exists, 28 sera from cysticercosis (21), paragonimiasis
      (5) or sparganasis (2) in Korea where no indigenous AE nor CE exists and 11
      normal sera. Antibody levels by PP-Em18/16-ELISA were much higher in AE than in
      CE and it was also true for commercially available Em2plus-ELISA. Some of CE from
      China showed exceptionally higher levels of antibody in comparison with those of
      CE from Australia. It is suggested that these strongly positive cases of CE from
      China may have been exposed to both species of Echinococcus. Although most of
      sera from paragonimiasis showed high antibody levels by Emplus-ELISA, they were
      negative by PP-Em18/16-ELISA. Therefore, PP-Em18/16-ELISA is expected to be more
      reliable for differentiation of AE from CE and others especially in Asian
      countries where paragonimiasis is still not rare. Antibody responses in rodents
      naturally infected with E. multilocularis: Serum samples from the wild vole,
      Clethrionomys rufocanus bedfordiae, infected with E. multilocularis showed
      similar antibody responses as in AE patients, whereas those from Norway rats,
      Rattus norvegicus, showed almost none. The latter rodents were simultaneously
      infected with Taenia taeniaeformis but showed no antibody response against T.
      taeniaeformis either. Therefore, we speculate that Norway rats may only be
      infected with E. multilocularis under some immunosuppressed conditions or genetic
      unresponsiveness. It is stressed that Em18 is highly specific to E.
      multilocularis, and antibody response against Em18 is reasonably reliable for
      differentiation of AE from other helminthic infections by Western blot and ELISA
      in humans and may be useful for detection of domestic animals contaminated with
      E. multilocularis in the endemic area.

PMID- 9656362
TI  - A study on the culture medium antigens of Cystcercus cellulosae for detecting
      antibodies of cysticercosis by means of ABC-ELISA.
AB  - Two antigens of Cysticercus cellulosae, cystic fluid antigen (CFA) and the
      culture medium antigen (CMA), were used in Avidin-Biotin Peroxdase Complex-ELISA
      (ABC-ELISA) to detect IgG antibodies in 45 cases of cysticercosis treated with
      praziquantel. The results revealed the total positive rates as 51.11% with CMA
      and 82.22% with CFA. The positive rates in the cases treated within 2 courses of
      treatment were 79.17% for CMA and 87.50% for CFA, and only 19.05% for CMA and
      71.43% for CFA in the cases treated for more then 3 courses. The fact that the
      positive rates decreased as the courses of treatment increased showed that the
      sensitivity of CMA might be related to the vital conditions of the worms in the
      body, whether alive or dead. It is, therefore, recommended that CMA has the
      potential to be employed in ABC-ELISA both as an indicator for diagnosing
      cysticercosis and as a reference for the evaluation of the treatment.

PMID- 9656363
TI  - Development and characterization of monoclonal antibodies against excretory
      secretory antigens of Fasciola gigantica.
AB  - Monoclonal antibodies (MAbs) directed against Fasciola gigantica excretory
      secretory (ES) antigens were developed from BALB/c mice. Four were selected for
      further study, from the panel of hybridomas. The antigen specificities of these
      MAbs were characterized and localized by enzyme-linked immunoeletrotransfer blot
      (EITB) and immunoperoxidase technique. The target epitopes of these MAbs are 66
      kDa protein (MAb 2D10), 66 and 27-26 kDa proteins (MAbs 5D10 and 4F5) and 27-26
      kDa protein (MAb 2D9). MAb 2D9 reacted to the antigenic components of the luminal
      content and epithelial cell lining the cecum, whereas MAb 2D10 reacted
      specifically to the antigens of the tegument and surface membrane. It was found
      that all MAbs cross-reacted to various degrees with the antigens extracted from
      Schistosoma mansoni, S. mekongi, S. spindale and Paramphistomum spp. However,
      when MAbs were diluted to 1:100 or 1:400 significant reduction of their cross
      reactivities was observed.

PMID- 9656364
TI  - Recent advances in diagnosis of paragonimiasis.
AB  - Paragonimiasis in endemic areas can be diagnosed by clinical symptoms. However,
      the diagnosis should always be confirmed by microscopic examination of the sputum
      or stool in order to find Paragonimus eggs. Within recent years marked advances
      in diagnosis of paragonimiasis have been made. Two new approaches comprising a
      genetic probe and immunological tests have been developed with claims to be as
      good or better than microscopic examinations. This report reviews these two
      areas, especially in paragonimiasis caused by Paragonimus heterotremus and P.
      westermani. In addition, problem areas in assay development are discussed.

PMID- 9656365
TI  - Detection of circulating antigens of Parastrongylus cantonensis in human sera by
      sandwich ELISA with specific monoclonal antibody.
AB  - A specific monoclonal antibody (AW-3C2) as revealed by ELISA was produced against
      the adult worm antigens of Parastrongylus cantonensis and used in a sandwich
      ELISA for the detection of circulating antigens in the sera of parastrongyliasis
      patients and those with other parasitic diseases. A total of 60 sera was used in
      this study. Of these, 10 each were from patients with parastrongyliasis
      filariasis, gnathostomiasis, malaria and toxocariasis. The control group
      consisted of 53 serum samples from normal healthy Thais and Malaysians. The mean
      +/- optical density (OD) values for the normal Thai and Malaysian groups were
      0.126 +/- 0.028 and 0.124 +/- 0.029, respectively. Mean OD values of
      parastrongyliasis patient group differed significantly from that of the normal
      groups as well as those of other parasitic infections. Using a cut-off point of
      mean OD +/- 3SD of the normal control groups as indicating a positive reading,
      the specificity of the assay with this monoclonal antibody was 100% while the
      sensitivity was 50%.

PMID- 9656366
TI  - Detection of Angiostrongylus malaysiensis circulating antigen using monoclonal
      antibody-based enzyme-linked immunosorbent assay (MAb-ELISA).
AB  - Three MAbs 1C4.2D8, 1C4.2C4 and 1C4.1F5 were produced using sonicated adult worm
      antigens of Angiostrongylus malaysiensis and they were found to be secreters of
      IgG1. The MAbs 1C4.2C4 and 1C4.2D8 were found to react with antigens of A.
      malaysiensis and cross-react with the closely related A. cantonensis but not with
      other helminths. A total of 108 human sera collected from Orang Asli (aborigenes)
      from Grik, in the State of Perak were tested for A. malaysiensis infection using
      the MAb-ELISA. MAb 1C4.1F5 and 25 (23%) were positive. Twenty of these positive
      samples were tested with the MAb 1C4.2D8 and none was found to be positive.

PMID- 9656367
TI  - Vaccine development against Theileria parasite.
AB  - Bovine piroplasmosis caused by Theileria sergenti is a major cause of economical
      loss in grazing cattle in Japan. We found that parasite stocks and isolates
      consist of genetically and antigenically mixed population. To differentiate
      parasite populations bearing 2 allelic forms of p32, an immunodominant piroplasm
      surface protein, 2 sets of oligonucleotide primers were designed to amplify
      either of the 2 alleles by polymerase chain reaction (PCR). By using this allele
      specific PCR, we found that the majority of T. sergenti-infected calves in Japan
      harbored mixed parasite populations with C and I type parasites. Amino acid
      sequence of p32 contains Lys-Glu-Lys (KEK) motif which is one of tripeptide
      necessary for malaria parasite to invade erythrocytes. We produced 2 vaccine
      candidates, recombinant baculovirus p32 and synthetic peptide containing KEK
      motif. Immunization of either recombinant p32 or synthetic peptide containing a
      KEK sequence with adjuvant resulted in low parasitemia and reduced the clinical
      symptoms compared to control calves. Interestingly, parasites with a p32 allelic
      form corresponding to one used as the immunogen were suppressed. Therefore, a
      cocktail vaccine containing KEK peptides derived from C and I type parasites is
      desired for control Theileria parasite infection in Japan.

PMID- 9656368
TI  - Observations on the effects of cysticercosis immune sera on cysticercosis by
      scanning electronmicroscopy.
AB  - Two antigens of Taenia solium cysticercus, cystic fluid antigen (CFA) and the
      culture medium antigen (CMA), were used respectively to immunize rabbits in order
      to obtain immunosera. The CMA immunoserum added to culture medium with cysticerci
      limited the activities of the bladder worms. By using the scanning
      electronmicroscope, we could observe particulate deposits on the surface of the
      scolices, suckers and necks of the worms. The CFA immunoserum group showed
      similar changes but the deposit was less than that on the worms in the former
      group and appeared mainly on the cystic wall. After adding complement to the two
      groups mentioned above, we found that the microcilia on the surface of the worms
      were swollen and were seriously damaged. The worms treated with praziquantel were
      damaged over large area of their surfaces and were affected deep into their
      tissues. The damaged parts of the worms were quite different between the two
      groups. CMA is secreted by the living worms and therefore the serum antibodies
      are more effective than CFA in anti-parasite activity.

PMID- 9656369
TI  - Ensuring hygienic quality of food of animal origin by irradiation processing.

PMID- 9656370
TI  - Irradiation as a cold pasteurization process of fish and seafood.

PMID- 9656371
TI  - Incidence of ascaridoid larvae in Kuwaiti food fishes.
AB  - Three hundred and six fish of 83 species were carefully examined in Kuwait during
      the period from October 1992 to September 1995 for ascaridoid larvae. Thirty-nine
      fishes (12.7%) belonging to 23 species were infected with 9 types of ascaridoid
      third-stage larvae: Anisakis simplex, Terranva spp, Contracaecum spp and 6
      different types of Hysterothylacium spp (KA-KF). Hysterothylacium larvae
      (including all types) were found in all the infected fish except one (94.6%);
      Terranova larvae were found in 12 fishes (10 species, 56.1%); Anisakis simplex
      larvae occurred in 2 fishes (2 species, 8.6%) and Contracaecum spp larvae in one
      fish only.

PMID- 9656372
TI  - A survey of bovine, bubaline and swine sarcocystosis in the Philippines.
AB  - In a survey conducted from January to December, 1994, muscle tissues in 12 out of
      22 slaughtered carabaos ages 8-17 years old and obtained from the Food Terminal
      Inc, Abbatoir in Laguna showed numerous white and creamy elliptic-shaped soft
      bodied macrocysts in the throat muscles. Microscopic examination of the throat
      and cardiac muscle tissues revealed the presence of fusiform-shaped microcysts.
      Our observations are consistent with previous reports incriminating Sarcocystis
      fusiformis as the most important etiologic agent of bubaline sarcocystosis in the
      country. In a survey of bovine sarcocystosis in muscle tissues of imported
      Australian cattle (Brahman Breed) and native cattle obtained from various
      slaughter houses in Manila and suburbs, prevalence rates of 17% (98/577) and 3%
      (1/31) were noted, respectively. Sarcocysts were predominant in skeletal muscles
      and to a lesser extent in cardiac, esophageal and diaphragm muscle tissues. Light
      microscopic examination of sarcocysts morphology suggests Sarcocystis cruzi (=
      Sarcocystis bovis), and Sarcocystis hominis (= Sarcocystis bovihominis) or
      Sarcocystis hirsuta (= Sarcocystis bovifelis) as the likely etiologic agents of
      bovine sarcocystosis in the country. Of the 225 swines examined, only muscle
      tissues from a 6-month old swine revealed very young sarcocysts (= metrocytes). A
      review of available documented studies on sarcocystosis suggests that to date,
      our findings may represent the first data on the prevalence of bovine and swine
      sarcocystosis in the Philippines.

PMID- 9656373
TI  - A survey of helminth infection in rats (Rattus spp) from Chiang Mai Moat.
AB  - An investigation of helminths in the Norway (brown) rat, Rattus norvegicus, and
      roof rat, Rattus rattus, from Chiang Mai Moat during May to August 1995, was
      done. Thirty-three out of thirty-eight trapped rats were infected (86.84%); 16 R.
      norvegicus (100%) and 17/22 R. rattus (77.27%). The rat was infected with 10
      helminth species: 4 trematodes, Centrocestus sp (2.63%), Echinostoma ilocanum
      (10.52%), Echinostoma malayanum (10.52%) and Quinqueseralis quinqueseralis
      (39.47%); 2 cestodes, Raillietina sp (36.64%) and Taenia sp (cysticercus)
      (7.89%); and 4 nematodes, Angiostrongylus cantonensis (42.10%). Nippostrongylus
      sp (34.21%), Rictularia sp (52.63%) and egg of Capillaria hepatica (7.89%). The
      helminths were found in the small intestine (84.21%), large intestine (42.10%),
      lung (36.64%), stomach (28.94%), heart (23.94%), and liver (15.78%). The female
      Norway rats were infected with 10 species of helminths and the males with 6
      species. In the roof rat, 7 species of helminths were found in females and 6
      species in males.

PMID- 9656374
TI  - Helminths in house lizards (Reptilia: Gekkonidae).
AB  - A survey of helminths in house lizards captured in Amphoe Maung, Chiang Mai
      Prouince revealed that the prevalence of helminthic infections in Cosymbotus
      platyurus was 94.4% and in Hemidactylus frenatus was 100%. Six species of
      helminths were found from C. platyurus: two species of trematodes,
      Posterochigenes sp (16.7%), Paradistomoides gregarium (41.1%); one species of
      cestode, Oochoristic sp (3.3%); two types of acanthocephalan cystacant, Type I
      (4.4%), type II (3.3%); and one species of nematode, Pharyngodon sp (83.3%). The
      cystacant Type II was not found in H. frenatus lizard, but the other five worms
      were found with higher prevalence. Pharyngodon was the common species in both
      lizards with the highest intensity range. So far, these worms have not been
      reported in human beings.

PMID- 9656375
TI  - Angiostrongylus infections in rats and snails in northeast Thailand.
AB  - A survey of Angiostrongylus infections in rats and snails was carried out in the
      provinces of Ubon Ratchathani, Udon Thani. Kalasin, Chaiyaphum and Khon Kaen in
      northeast Thailand. Only two Rattus norvegicus (3.8%) and one Bandicota indica
      (1.4%) out of 151 R. rattus, 52 R. norvegicus and 69 B. indica examined were
      infected with adult lung worms. All worms recovered were A. cantonensis.
      Prevalence of infection in 423 Pila polita was 0.9% while all of 77 P. ampullacea
      were negative for larvae. In contrast to this 36.4% of 500 Achatina fulica
      harbored L3 of Angiostrongylus (with variations of between 29% and 46% in the
      five provinces). The average infection intensity in A. fulica was 13.6 L3 (1 to
      441). Experimental infection of Wistar rats with L3 (isolated from A. fulica
      resulted in a recovery rate of 48.3% of adult worms of which 91.7% and 8.3% were
      identified as A. cantonensis and A. malaysiensis, respectively. This is the first
      proven finding of A. malaysiensis in northeast Thailand.

PMID- 9656376
TI  - An outbreak of ascariasis with marked eosinophilia in the southern part of Kyushu
      District, Japan, caused by infection with swine ascaris.
AB  - Ascariasis has been a representative soil-transmitted intestinal parasitic
      disease in warm climates. In Japan, this disease was a major and serious public
      health problem only a few decades ago. However, the incidence of the disease
      nowadays is reportedly less than 0.01%. Recently in 1994 through 1995, we
      experienced a total of 14 cases who were suspected as having ascariasis. They
      were characterized by peripheral blood eosinophilia (30-70%), high serum titers
      against Ascaris antigen, and most notably, they were absolutely negative for
      Ascaris eggs in repeated fecal examinations. Specific antibody titers against
      Ascaris antigen correlated well with the degree of eosinophilia. All patients
      were living in narrow areas of Kyushu, Japan, where a lot of porcine farms were
      located. Most of the patients were asymptomatic and pointed out to have
      eosinophilia during follow-up studies of chronic diseases or in regular check-up.
      Only one patient had a clear sign of Loffler's syndrome and another had
      subcutaneous eosinophilic granuloma. However, laboratory examinations revealed
      moderate liver dysfunction in 7 patients and pulmonary infiltrations in 5
      patients. Based on circumstantial and serological evidence, these patients were
      diagnosed as having been infected with Ascaris lumbricoides suum, a swine
      Ascaris.

PMID- 9656377
TI  - Newly recognized causative larval nematode (Suborder :Spirurina) of creeping
      eruption.

PMID- 9656379
TI  - Natural infection of trematodes in Lymnaea (Radix) auricularia rubiginosa in
      water reservoirs in Amphoe Muang, Khon Kaen Province.
AB  - Lymnaea (Radix) auricularia rubiginosa (Michelin, 1831) was surveyed in 54
      reservoirs of 18 districts in Amphoe Muang, Khon Kaen Province during February to
      May 1994. Lymnaeid snails were found in the water of 20 reservoirs, of which 16
      reservoirs contained clear water and 4 turbid water. Two of the four turbid water
      reservoirs received drainage water from Khon Kaen Town. Two thousand four hundred
      and eight L. auricularia rubiginosa were collected and examined by shedding and
      crushing. Trematode infection occurred in 163 (6.77%) of 2,408 L. auricularia
      rubiginosa and some snails were infected with more than one cercarial species.
      Ninety-nine snails (4.11%) were infected with echinostomes, while mixed infection
      of echinostomes with Fasciola gigantica and with schistosomes was found in 5
      snails (0.21%) and 2 snails (0.08%), respectively. Only 1 snail (0.04%), 19
      snails (0.79%) and 37 snails (1.54%) were infected with F. gigantica,
      schistosomes and unidentified species, respectively. The mean size of infected
      snails was 6.89 +/- 2.02 mm (6.20-22.36) while the mean of sampled snails was
      13.46 +/- 3.64 mm (4.00-26.55). The water plants which were found in reservoirs
      and presented with snails, were creeping water primose (Jusstaea repens), water
      lily (Nymphaea sp), water hyacinths (Eichornia crassipes) and grass.

PMID- 9656378
TI  - Planorbid snails as potential molluscan intermediate host of a human intestinal
      fluke, Neodiplostomum seoulensis (Trematoda : Diplostomatidae) in Korea.
AB  - Three species of the pulmonate snails of the family Planorbidae have been
      reported from Korea; Gyraulus convexiusculus, Hippeutis (Helicorbis) cantori and
      Segmentina (Polypylis) hemisphaerula. Of these 3 species, only H. cantori is
      reported as the molluscan intermediate host of Neodiplostomum seoulensis, one of
      the important snail-borne human intestinal trematodes in Korea. However, S.
      hemisphaerula was also found to be an intermediate host for N. seoulensis. In
      field-collected snails, H. cantori and S. hemisphaerula were found shedding
      bifurcated cercariae of N. seoulensis, whereas no G. convexiusculus was found
      shedding cercariae. In experiments with laboratory-bred snails, only S.
      hemisphaerula was susceptible to miracidia of N. seoulensis. Tadpoles of Rana
      nigromaculata and R. rugosa were exposed to cercariae shed from field-collected
      and laboratory-bred S. hemisphaerula. All tadpoles of R. nigromaculata were found
      to be massively infected, but none of the tadpoles of R. rugosa were infected
      with larvae of N. seoulensis. Metacercariae from tadpoles of R. nigromaculata and
      the snake Rhabdophis tigrinus tigrinus were fed to rats, and eggs of N.
      seoulensis were detected in the rat feces one-week later. These rats were killed
      and adult N. seoulensis recovered from the small intestines. This is the first
      report of S. hemisphaerula as a molluscan intermediate host for N. seoulensis in
      Korea.

PMID- 9656380
TI  - Light and scanning electron microscopy of Stellantchasmus sp (Trematoda :
      Heterophyidae).
AB  - Light and scanning electron microscopy of heterophyid fluke, Stellantchasmus sp
      were studied. The adults were obtained from Rattus norvegicus, 7 days after
      experimental infections with the metacercariae from the body cavity of Dermogenus
      pusillus. Living specimens and stained flukes were examined by light microscope.
      The present worm differed from S. batillans having a single testis while testes
      of S. gallinte were tandam. It is closed to S. falcatus and S. aspinosus but can
      not be identified to species because of acetabular spines. The tegumental surface
      by SEM was investigated on encysted metacercariae and adults. It was nearly
      smooth with one end shallow wide groove of the metacercarial surface. The entire
      surface of adult worms were almost covered with scale-like spines, pectinate, 7-9
      teeth. The size of scale was largest in the middle of body and decreased both
      anterior and posterior. No spines were around the excretory pore but has a
      wrinkled surface appearance. The dorsal surface appeared to have scale-like
      spines and pectination on the ventral surface. The papillae consisted of a single
      club-like cilium, solitary or grouped on the anterior part of the body especially
      anterior of oral sucker. Acetabulum located slightly right of the middle and
      invagination.

PMID- 9656381
TI  - Annual economic loss caused by Taenia saginata asiatica taeniasis in three
      endemic areas of east Asia.
AB  - The Taenia saginata-like tapeworm in East Asia has been designed as a separate
      subspecies of T. saginata. It was named as T. saginata asiatica and the classical
      T. saginata as T. saginata saginata. In the course of conducting experimental
      infections and morphological studies, a large number of adult worms of T.
      saginata asiatica was collected. It is possible to estimate the annual economic
      loss caused by this infection, since the worm load and the weight of worm habored
      by each infected person were determined from the collection. In the mountainous
      areas of Taiwan, the infection rate of T. saginata asiatica taeniasis was 11.0%,
      the worm load was 1.6 worms/case, and the average weight of an adult worm was
      20.5 g. The annual economic loss was estimated to be US$ 11,327,423. On Cheju
      Island of Korea, the infection rate was 6.0%, the worm load was 2 worms/case, and
      the average weight of an adult worm was 19.3 g. The annual economic loss was
      estimated to be US$ 13,641,021. On Samosir Island of Indonesia, the infection
      rate was 21%, the worm load was 1.8 worms/case, and the average weight of an
      adult worm was 22 g. The annual economic loss was estimated to be US$ 2,425,500.
      These figures indicate that taeniasis is not only a significant public health
      problem but also an important economic problem in East Asia.

PMID- 9656382
TI  - Metacercariae in fishes of Sun Moon lake which is an endemic area for Clonorchis
      sinensis in Taiwan.
AB  - The Sun Moon lake in Central Taiwan is a known endemic area for clonorchiasis. Of
      the 45 fresh water fish, Hemiculter leucisculus, from the lake that were examined
      by artificial gastric juice digestion in October 1995, all were found to harbor
      metacercariae in their muscle. The number of metacercariae isolated from each
      fish ranged from 2 to 2,185, with an average of 254. A total of 11,443
      metacercariae was collected from the 45 fish. Of the 4,223 metacercaria that were
      examined under light microscope, 4,064 (96.23%) were found to belong to
      Haplorchis taichui, 90(2.13%) to H. pumilio, 2(0.05%) to C. sinensis and 67
      (1.59%) to unknown species due to the metacercariae being not yet developed or
      immature. The 2 C. sinensis metacercariae were obtained from 2 out of 45 fish
      examined. Our results contrast with reports of a decade ago which stated that all
      the fish of the Sun Moon lake examined were positive for C. sinensis. Possible
      reasons for the decrease of C. sinensis metacercariae are the disappearance of
      pig farms around the lake, increased awareness of the trematode by the lakeside
      inhabitants and probably the exclusive use of mammals as its definitive host by
      C. sinensis. In contrast, besides mammals, Haplorchis spp also use birds as their
      definitive hosts.

PMID- 9656383
TI  - Metacercariae isolated from cyprinoid fishes in Khon Kaen District by digestion
      technic.
AB  - Several kinds of fresh-water fishes collected from natural water resources in
      Khon Kaen District were digested with 0.25% pepsin A to obtain the infective
      stage or metacercariae of fish-borne trematodes. Most of them harbored at least 3
      species of trematodes. Two families of medical trematodes, i.e., Family
      heterophyidae and Family Opisthorchiidae, were isolated. The heterophyid flukes
      consisted of Haplorchis taichui, H. pumilio and Centrocestus formosanus.
      Opisthorchis viverrini was the only parasite of the Family Opisthorchiidae found
      in these fish. Among these four species, H. taichui was predominant and found in
      all kinds of fish examined, especially Hampala dispar.

PMID- 9656384
TI  - Playing with fire.

PMID- 9656385
TI  - Does hepatitis G virus cause significant clinical liver disease?
AB  - Regarding the newly discovered hepatitis G virus (HGV), little is known about its
      relation to the cause and clinical significance of acute and chronic liver
      disease and hepatocellular carcinoma. Lacking a reliable serum immunoassay, the
      only method available for detecting the viral RNA in patients consists of the
      rather costly and time consuming RT-PCR. HGV has a worldwide distribution with up
      to 5% voluntary and 12.9% commercial blood donors infected, yet it appears to be
      asymptomatic. Moreover, HGV is frequently found as a coinfection with HCV or, to
      a lesser extent, HBV with symptoms tending to follow the patterns known for HCV
      or HBV infection, respectively. Being a blood-borne virus, it is most prevalent
      among members of high risk groups, such as IVDUs, patients on hemodialysis,
      recipients of blood and blood products and patients infected with HCV, HBV, or
      HIV, HGV can be parenterally, vertically, or sexually transmitted and after
      prolonged exposure, the virus may be eliminated by the patient's immune response.
      As yet, no unambiguous evidence exists regarding HGV's role in causing acute or
      chronic liver disease and, apart from a few isolated reports to the contrary, the
      infections appear rather mild. Therefore, more studies are required before a
      decision can be made whether to routinely screen blood donors for the presence of
      HGV RNA.

PMID- 9656386
TI  - Hepatitis B and C virus infection prevalence among women in Manila, the
      Philippines.
AB  - A seroepidemiological survey of HBsAg, HBeAg, anti-HBs, anti-HBc, anti-HBe and
      anti-HCV positivities was conducted in 1997 in Manila, The Philippines. Adult
      women (21 to 59 years of age) were invited to donate peripheral blood for the
      study, and 50 people volunteered. They were nonsmokers, nonhabitual drinkers, and
      mostly married; none of them was a professional blood donor. The serum assay
      showed that all subjects were negative for HBsAg and HBeAg. Overall, a half (50%)
      of the study subjects were positive for any one of the HBV infection markers
      (i.e. HBV+). The older group (25 women at 36-59 years of age) showed
      significantly higher prevalence than the younger group (25 women at 21-35 years
      of age) of positivity to all three HBV antibody markers and therefore HBV
      positivity also. None of the study subjects was positive for anti-HCV. Comparison
      of the present findings with the results reported in the literature for the 1980s
      suggests that the risk of HBV infection and most probably that of HCV infection
      also has decreased in this 10-year period in the Philippines.

PMID- 9656387
TI  - Maternal and viral factors in vertical transmission of HIV-1 subtype E.
AB  - Vertical transmission of HIV-1 is caused by multifactorial factors. To access the
      relationship of viral factors involving in perinatal transmission of HIV-1
      subtype E, which is the predominant type in Thailand, plasma viral load, blood
      CD4+ lymphocyte level, heteroduplex mobility, and V3 sequence of the HIV-1
      envelope gene were studied in 32 transmitting and 25 non-transmitting mothers. We
      found that HIV-1 subtype E vertical transmission was strongly associated with
      high maternal plasma viral RNA (> 4 x 10(4) copies/ml) and high genetic diversity
      of envelope gene determined by heteroduplex mobility (< 0.9). The variation of
      nucleotide sequences in envelope gene of subtype E vertical transmission could
      not determine in V3 region. Hence, plasma viral load and heteroduplex mobility
      can be used as prediction factors in vertical transmission of HIV-1 subtype E.

PMID- 9656388
TI  - Prevalence of transfusion associated infections in multitransfused children in
      relation to mandatory screening of HIV in donated blood.
AB  - Any change in risk behavior related to acquisition of human immunodeficiency
      virus (HIV) infection is likely to reduce simultaneously the risk for other
      agents transmitted through identical routes. A study carried out in the city of
      Delhi, India on the load of transfusion associated infections among
      multitransfused (MT) children in relation to mandatory screening of HIV infection
      in donated blood indicated unchanged prevalence of hepatitis B virus (HBV),
      hepatitis C virus (HCV) and hepatitis D virus (HDV) infections among the group of
      MT children transfused after the implementation of mandatory screening of HIV
      infections in blood banks, i.e. post-implementation period (prevalence of HBV,
      HCV and HDV being 32.8%, 31.3% and 1.6% respectively) compared to a group of MT
      children transfused over a similar duration before the implementation of
      mandatory screening i.e. pre-implementation period (prevalence of HBV, HCV and
      HDV being 28.1%, 26.6% and 1.6% respectively). However, reduction could be
      recorded in the prevalence of IgM and IgG classes of antibodies to both CMV and
      HSV-2 infections among MT children receiving transfusion during the post
      implementation period (prevalence of 3.1% and 37.1% for CMV IgM and CMV IgG
      respectively; prevalence of 3.1% and 25% for HSV-2 IgM and HSV-2 IgG,
      respectively) compared to the group of MT children transfused in the pre
      implementation period (prevalence of 15.6% and 56.3% for CMV IgM and CMV IgG
      respectively; prevalence of 18.8% and 45.2% for HSV-2 IgM and HSV-2 IgG,
      respectively). These reductions were statistically significant (p values < 0.02
      and < 0.05 for CMV IgM and CMV IgG; p values < 0.01 and < 0.02 for HSV-2 IgM and
      HSV-2 IgG respectively). These observations were in accordance with the recorded
      reduction in the prevalence of CMV and HSV-2 infections and unaltered prevalence
      of HBV, HCV and HDV infections in the group of donors donating blood during the
      post-implementation period compared to those donating in the pre-implementation
      period. Study of epidemiological risk factors among blood donors showed a change
      in behavior towards safer sex practice with only 13.0% of donors in the post
      implementation period having history of sex with one or more female commercial
      sex workers during their donation periods compared to 41.5% of donors in the pre
      implementation period having similar history (p < 0.001). However no change could
      be recorded in the proportion of donors donating at frequency higher than the
      permissible guidelines among the two groups. The present study points out
      nosocomial transmission as well as limitations in the existing guidelines for
      screening of infectious agents in blood banks as possible incriminating factors
      towards acquisition of hepatitis virus infections in blood donors as well as in
      MT children.

PMID- 9656389
TI  - Detection and typing of human papilloma virus DNAs in normal cervix,
      intraepithelial neoplasia and cervical cancer in Bangkok.
AB  - We detected and typed HPV-DNA by polymerase chain reaction (PCR) in cervico
      vaginal lavages of 102 women with normal cervical cytology, 57 patients with
      cervical intraepithelial neoplasia (CIN), and 23 cervical cancer patients. HPV
      DNA detection and typing by in situ hybridization were also performed in cervical
      biopsies from CIN lesions and cancers. Five percent of women with normal cervical
      cytology, 46% of CIN, and 61% of cervical cancer were positive for HPV-DNA. Of
      CIN cases with positive HPV-DNA, 69, 15, 8, 4 and 4% were HPV-16, -33, -18, -11
      and -16/33 respectively. Of cervical cancer cases with positive HPV-DNA, 86% were
      HPV-16, 7% were HPV-16/33, 7% were HPV-18/31. HPV typing was performed in
      biopsies from 37 CIN and 18 cervical cancers by in situ hybridization. By this
      method, 38% of CIN were HPV-DNA positive, of which 71% were HPV-16 and 7% were
      each of HPV-11, -18, -31 and -33. Thirty-nine percent of cervical cancers were
      positive, of which 71% and 29% were HPV-16 and HPV-16/18 respectively.

PMID- 9656390
TI  - The cost of dengue hemorrhagic fever in Thailand.
AB  - The economic burden of DHF patients and of the Thai government in providing
      treatment and prevention and control of dengue hemorrhagic fever were assessed.
      Patient burden was reported by caretakers who stayed with the patients when they
      were admitted to three hospitals: Children's Hospital in Bangkok; Suphan Buri
      Provincial Hospital and Don Chedi Community Hospital, Don Chedi District in
      Suphan Buri Province. The hospital costs--medicine and laboratory costs--were
      collected from the treatment forms and the routine service cost was estimated by
      the staff of the hospitals. Cost of prevention and control were compiled from the
      budget report of Departments of the Ministry of Public Health and the Ministry of
      Interior. Based on 184 DHF patients admitted at the three hospitals, the direct
      patient costs--treatment cost and the costs of travel, food and lodging--was
      66.99 US$ and 61.02 US$ per patient for one episode of DHF in Bangkok and Suphan
      Buri, respectively. The total patient costs--direct patient costs and opportunity
      costs were 118.29 US$ for a child patient and 161.49 US$ for an adult patient in
      Bangkok, 102.82 US$ for a child patient and 138.02 US$ for an adult patient in
      Suphan Buri. The net hospital cost in providing treatment for each DHF patient
      was 54.6 US$ and 38.65 US$ in Bangkok and Suphan Buri, respectively. The total
      cost of prevention and control of DHF in Thailand from government agencies in
      1994 was 4.8724 million US$. Based on these findings, the whole expenditure of
      Thailand for DHF in 1994, would be at least 12.596 million US$, of which 54.8%
      was from the government budget, the rest, 45.2%, was the expenses paid by 51,688
      patients and their families. The study concluded that in recording the economic
      loss of DHF both the expenditures of the government and also the patient costs-
      direct and indirect--should be taken into account.

PMID- 9656391
TI  - The effect of nonionic detergent on dengue and Japanese encephalitis virus
      antigens in antigen detection ELISA and IgM-capture ELISA.
AB  - In order to simplify dengue and Japanese encephalitis (JE) IgM-ELISA, we have
      been trying to produce antigens as infected C6/36 cell culture fluid. In this
      study, we examined the effect of nonionic detergents, which were used to
      inactivate viral infectivity, on dengue and JE antigen titers as well as the
      results in an IgM-capture ELISA. In the antigen detection ELISA, antigen titers
      were not significantly reduced after treatment with nonionic detergents (Nonidet
      P-40 or Triton X-100, at 0.01 to 0.1% final concentration). In contrast, in the
      IgM-capture ELISA, the color development was significantly reduced when the
      antigens were pretreated with nonionic detergents. The results suggest that
      certain epitopes which react with anti-viral IgM antibodies, but not IgG
      antibodies, have been destroyed by treatment with nonionic detergents. The
      results indicate that we cannot use nonionic detergents to inactivate the
      infectivity of assay antigens.

PMID- 9656392
TI  - The ICT Malaria Pf: a simple, rapid dipstick test for the diagnosis of Plasmodium
      falciparum malaria at the Thai-Myanmar border.
AB  - The ICT Malaria Pf test for the detection of Plasmodium falciparum infection was
      evaluated in the diagnosis of 305 patients with fever who were admitted to a
      hospital located on the Thai-Myanmar border. All patients were admitted for at
      least one week to exclude reinfection. The test was performed using admission
      blood samples collected into ethylenediaminetetraacetic acid. The sensitivity,
      specificity and accuracy of the test were 92.7%, 95.1% and 94.7% respectively,
      compared to standard microscopic diagnosis. The ICT Malaria Pf test is an
      accurate method for the diagnosis of P. falciparum infection. Its simplicity and
      rapidity make it particularly appropriate for use in remote areas where
      microscopic examination of blood films is unavailable.

PMID- 9656393
TI  - Two doses of artemether/mefloquine or artesunate/mefloquine combination for
      multidrug resistant falciparum Malaria.
AB  - Plasmodium falciparum in Southeast Asia is highly resistant to chloroquine,
      sulfadoxine/ pyrimethamine, quinine and even mefloquine. The use of two doses of
      short course artemether/mefloquine combination has been shown to be effective in
      a recent study. In the present study, we have assessed the efficacy of short
      course treatment with artesunate/mefloquine, in comparison with
      artemether/mefloquine in patients with multidrug resistant falciparum malaria.
      Ninety-nine Thai male patients who sought consultation at Makham Malaria Clinic,
      Chantaburi (eastern part of Thailand), were randomized to receive either the
      combination of artemether (150 and 100 mg; group A) or artesunate (150 and 100
      mg; group B) with mefloquine (750 and 500 mg) at 24 hours apart. The follow-up
      was on days 1, 2, 7, 14, 21, 28, 35 and 42. Patients in both groups showed a
      rapid initial response to treatment; fever and parasite were cleared within 48
      hours in 100 and 100% vs 91.8 and 96%, for group A vs B, respectively. All
      patients in group A had completed the 42 day-follow up; however, two patients in
      group B did not finish the 42-day follow-up. The cure rate was 100% in either
      group. No serious adverse effects were found. Artemether or artesunate with
      mefloquine given two doses at 24 hours apart can be used as effective alternative
      treatment regimens for multidrug resistant falciparum malaria.

PMID- 9656394
TI  - Pharmacokinetics and ex vivo anti-malarial activity of sera following a single
      oral dose of dihydroartemisinin in healthy Thai males.
AB  - The pharmacokinetics of dihydroartemisinin (DHA) was studied in eight healthy
      male Thai subjects after a single oral dose of 300 mg. Absorption of oral DHA was
      rapid, Cmax of 679 (307-1000) ng/ml was observed at 1.5 (1-2.5) hours after
      dosing [median (range)]. Plasma concentrations declined monoexponentially and at
      12 hours after administration, the levels were below the detection limit (3
      ng/ml). A large variation in the AUC (approximately) 50% was observed. The median
      (range) AUC was 2010 (636-4079) ng h/ml. The lag time and absorption half-life
      (t1/2a) were 0.169 (0.111-0.277) hours and 0.709 (0.367-1.118) hours
      respectively. t1/2z was 1.25 (0.79-1.89) hours Vz/f and CL/f were 5.9 (3.5-8.2)
      l/kg and 45.3 (28.6-122.8) ml/min/kg, respectively. The pattern of its ex vivo
      serum activity coincided with the plasma concentrations of DHA.

PMID- 9656395
TI  - Artemether in moderate to severe malaria: a multicenter trial in India.
AB  - 154 patients suffering from acute attack of moderate to severe malaria caused by
      Plasmodium falciparum were treated with 480 mg artemether, administered
      intramuscularly (i.m.) in six equally divided doses at 12 hour intervals. Results
      showed a rapid parasite clearance. Mean parasite clearance time (PCT) was found
      to be 23.65 +/- 1.57 hours. Mean fever clearance time (FCT) was 35.28 +/- 1.7
      hours. Adverse drug events (ADE) were mild and self-limiting. Recrudescence rate
      (RR) among the patients followed up was 4.55%. We conclude that artemether is a
      safe and effective anti-malarial agent for the treatment of moderate and severe
      cases of P. falciparum malaria.

PMID- 9656396
TI  - Transplacental passage of Plasmodium falciparum and seroevaluation of newborns in
      northern Nigeria.
AB  - The findings of a prospective study of 656 near-term pregnant; women, and of the
      cord and peripheral blood of newborns of positive mothers are reported. 292
      (44.51%) of the pregnant women were infected with Plasmodium falciparum. Further
      microscopic screening of the cord blood of newborns of the 292 positive cases at
      delivery showed a parasite rate of 10.95%. Transplacental passage of P.
      falciparum was confirmed by detection of parasitemia in the peripheral blood of
      2.82% of newborns within 7 days of birth. Serological investigation of sera of
      284 newborns by indirect fluorescent technic (IFA) with P. falciparum IgM
      specific conjugate indicated that 72 (24.66%) had IgM antibodies of P. falciparum
      in their blood. The average birthweight of seropositive newborns was 400 g less
      than seronegative ones. There was no significant difference in the rate of
      neonatal infection regardless of whether or not the mothers had taken chloroquine
      prophylaxis.

PMID- 9656397
TI  - Plasmodium ovale in Lao PDR.

PMID- 9656398
TI  - Immune response against the non-repeat region (293-310) of the circumsporozoite
      protein of Plasmodium vivax.
AB  - Immunization by peptides based on the repeat sequences of Plasmodium falciparum
      or P. vivax antigen(s) have shown inconsistent results during clinical trials in
      humans. This could be attributed to the lack of T-cell help or antigenic
      polymorphism. Thus, attention has been focused towards the more conserved non
      repeat regions. The present study was undertaken to map the antigenic determinant
      in the vicinity of region II (outside the repeat) of CS protein of P. vivax. The
      immunogenicity of the peptide was studied alone and after linking with
      polytuftsin (PT), using alum and Freund's adjuvant, in inbred strains of mice
      with different genetic backgrounds. The humoral response and antigen induced T
      cell proliferation assays clearly demonstrated the immunomodulatory activity of
      PT. Comparable results were observed with antigen(s) administered either in alum
      or Freund's adjuvant. The induction of IgG2a and IgG2b antibody isotypes by both,
      peptide as well as the conjugate, may indicate that the T-helper response
      involved is of Th1 type. Further the immunofluorescence studies have shown that
      antibodies recognized the air dried sporozoites of P. cynomolgi. The results thus
      show that the above sequence has overlapping B and T-cell determinants and that
      alum can be substituted for Freund's adjuvant in generating an effective immune
      response.

PMID- 9656399
TI  - Granulocyte-macrophage colony-stimulating factor production by T lymphocytes in
      Plasmodium berghei-infected mice.
AB  - The production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by
      lymphocytes was examined in murine malaria. When spleen cells or lymph node cells
      from P. berghei-infected mice were cultured in vitro with malaria antigen, the GM
      CSF production correlated with the incubation time up to 72 hours. When
      lymphocytes obtained at various days after infection were cultured with the
      antigen, GM-CSF became detectable as early as 2 days after infection, reached a
      peak at day 9 and then rapidly decreased. Production of GM-CSF was antigen
      specific, and related to the dose of antigen. Treatment of lymphocytes with anti
      Thy-1.2 antibody and complement resulted in almost complete loss of GM-CSF
      producing activity, while treatment with either anti-CD4 or anti-CD8 antibody and
      complement resulted in partial loss of GM-CSF-producing activity, indicating that
      both CD4+ and CD8+ T cells are involved in GM-CSF production in malaria. GM-CSF
      exhibits glycoprotein nature, and has an apparent molecular weight of 36,000. The
      molecular properties of this T-cell derived GM-CSF were compared with those of
      known lymphokine GM-CSF.

PMID- 9656400
TI  - Immune response profile in patients with active tuberculosis in a BCG vaccinated
      area.
AB  - Tuberculosis patients with pulmonary (N = 95) or lymph node disease (N = 23) were
      assessed for Th1 responses (PPD skin test and lymphocyte blastogenic and
      interferon gamma) and Th2 responses (polyclonal and antigen specific IgE). Skin
      test responses to PPD and lymphocyte proliferative responses to crude
      mycobacterial antigens (PPD, culture filtrate and sonicate) and recall antigens
      (tetanus toxoid and streptolysin O) were significantly suppressed (p < 0.001) in
      patients with pulmonary disease compared to endemic controls. However, mitogen
      (phytohemagglutinin)-stimulated responses were comparable in patients and
      controls. Polyclonal and antigen specific (M. tuberculosis culture filtrate) IgE
      responses which are considered to be surrogate markers for Th2 responses were
      significantly higher in patients with pulmonary disease compared to healthy
      endemic controls (Mann Whitney analysis p < 0.01). Patients with lymph node
      disease showed strong Th1 responses but did not show significant responses for
      either polyclonal or antigen specific IgE. Thus overall suppression of T cell
      memory response was observed only in patients with pulmonary disease but not in
      patients with lymph node disease suggesting that sequestration of antigen in
      different compartments leads to differential activation of Th1 and Th2 responses.
      PPD skin test responses were highly positive in endemic controls (47% positive)
      and household contacts (86% positive). Furthermore, PPD positivity decreased with
      disease severity. Therefore PPD positivity in a BCG vaccinated TB endemic area
      cannot be used as a diagnostic marker for active tuberculosis particularly in
      advanced disease.

PMID- 9656401
TI  - Demographic data on Salmonella enteritidis infection in Thailand, 1990-1995.
AB  - The data for the comprehensive analysis of Salmonella enteritidis infection was
      based on the information recorded in the request form submitted for Salmonella
      typing and the results of serotyping at the WHO National Salmonella and Shigella
      Center, Department of Medical Sciences, Ministry of Public Health, Thailand
      during 1990-1995. Fifty-one cases of S. enteritidis (SE) infection were confirmed
      in 1990. The morbidity being markedly increased each year from 1991 to 1995, with
      105, 307, 471, 659 and 877 cases being identified, respectively. Among the
      isolates of Salmonella spp, SE was the most common serotype during 1993-1995. The
      cases were mostly predominant in Bangkok and then in southern, northeastern,
      central and northern regions, respectively. The morbidity rates per 100,000
      population per year of SE infection in 1990-1995 were 0.09, 0.18, 0.53, 0.8, 1.11
      and 1.47, respectively. Analysis of the infection rate by sex and age
      demonstrated that the incidence in males was higher than in females. Adult
      patients were more frequently found than adolescent patients. The organism was
      found in feces, blood, pus, urine, cerebrospinal fluid and sputum, accounting for
      41.7, 35.8, 5.5, 2.5, 1.7 and 0.4%, respectively. The average extraintestinal
      isolation index was 0.52.

PMID- 9656402
TI  - Specific binding of Burkholderia pseudomallei cells and their cell-surface acid
      phosphatase to gangliotetraosylceramide (asialo GM1) and gangliotriaosylceramide
      (asialo GM2).
AB  - Specific binding between bacterial cells and host tissue is an early step of the
      pathogenesis of infection. Burkholderia pseudomallei cells, the causative micro
      organisms of melioidosis, were demonstrated to bind specifically to tissue
      glycolipids (asialo GM1 and asialo GM2) by solid phase binding assay on thin
      layer chromatograms. The detection limit was around 400 pmol of the glycolipids.
      Acid phosphatase purified from the culture filtrate of B. pseudomallei was tested
      for such binding properties, and the same results were obtained. According to our
      previous studies, the enzyme is a glycoprotein located on the cell surface, and
      hydrolysed tyrosine phosphate most actively among the substrates so far tested.
      The mode of binding between the enzyme and the glycolipids was analyzed by
      comparison of binding levels among three samples different in protein content,
      sugar content and specific phosphatase activities per protein and sugar residue.
      The results suggested the possibility of a receptor-ligand relationship between
      the bacterial enzyme and the host-cell glycolipids (asialo GM).

PMID- 9656403
TI  - An assessment and evaluation of methods for diagnosis of chlamydial and
      gonococcal infections.
AB  - Chlamydia trachomatis and Neisseria gonorrhoeae were studied in 350 females and
      140 males attending the sexually transmitted disease clinic and AIDS Center, Khon
      Kaen zone 6 and the Division of Obstetrics and Gynecology, Khon Kaen Hospital.
      Chlamydia trachomatis infection was diagnosed by cell culture (CC), enzyme
      immunoassay (EIA) (Bioquest, NSW, Australia) and nucleic acid hybridization
      (PACE2 system: Gen-Probe, San Diego, Calif). It was found that the sensitivity,
      specificity and positive and negative predictive values in females were 95.7,
      100.0, 100.0, 99.7% by the cell culture; 91.3, 99.1, 87.5, 99.4% by the EIA; and
      78.3, 99.7, 94.7, 98.5% by the PACE2 respectively. Values of the same parameters
      in males were 83.3, 100.0, 100.0, 98.5% by the cell culture; 75.0, 99.2, 90.0,
      97.7% by the EIA and 91.7, 100.0, 100.0, 99.2% by PACE2 respectively. The methods
      for detection of Neisseria gonorrhoeae infection were conventional culture, PACE2
      test and the direct examination (Gram's stain). In females, the sensitivity,
      specificity and positive and negative predictive values of the conventional
      culture were 85.7, 100.0, 100.0, 99.7% and those of the PACE2 were 85.7, 99.1,
      66.7, 99.7% respectively. In males, the values of the same parameters were 81.8,
      100.0, 100.0, 100.0% by the conventional culture, 95.5, 100.0, 100.0 and 99.2% by
      the PACE2. The prevalence of chlamydial infection in females was 6.6% (23/350)
      and that in males was 8.6% (12/140). The prevalence of gonococcal infection in
      females was 2.0% (7/350) and in males was 15.7% (22/140). The co-infection of
      Chlamydia trachomatis and Neisseria gonorrhoeae in females was 0.9% (3/350) and
      no co-infection was found in males. It is concluded that cell culture is an
      appropriate method for detection of Chlamydia trachomatis in both genders,
      particularly in females. PACE 2 test is the best method for such detection in
      symptomatic males while EIA is a good method in females, particularly in
      symptomatic females. For gonococcal detection, PACE2 test is a sensitive,
      specific and alternative method to the conventional culture. It can be
      appropriately applied for the diagnosis of gonococcal infection, particularly in
      males.

PMID- 9656404
TI  - Retrospective study of empyema cases in National Pediatric Hospital, Cambodia.
AB  - Majority of empyema cases admitted into the National Pediatric Hospital (NPH),
      Cambodia were of bacterial origin (EB: 95%), the rest were caused by tuberculosis
      bacilli (ETB: 5%). The morbidity of overall empyema, empyema of bacterial origin
      and empyema of TB origin between boys and girls was the same, even though boys
      were more likely to be exposed than girls. The mean age of patients with ETB was
      significantly greater than those of EB, 84.7 +/- 46 months versus 52.5 +/- 37
      months. Since NPH is located in Phnom Penh, most of our cases were from Kandal,
      Phnom Penh, and provinces nearby. On average all of the patients stayed in the
      hospital for 23.26 +/- 14.9 days (rank 1-91 days), and the mean duration of
      hospitalization of the ETB patients was significantly longer than that of EB
      patients, 32 +/- 19 days versus 22 +/- 14 days respectirely. The yearly incidence
      of empyema cases in 1990-1993 had the trend of slightly increased frequency
      during March to May. The overall EB case fatality rate was 3%, contributed to by
      delayed referral of cases.

PMID- 9656405
TI  - Ofloxacin containing combined drug regimens in the treatment of multibacillary
      leprosy.
AB  - The results of ofloxacin containing combined drug regimens in the treatment of 60
      multibacillary leprosy cases from January 1989 to June 1995 are reported. The
      objective of the trial is to compare the antileprotic property of ofloxacin and
      rifampicin in multibacillary leprosy patients and to study the killing rate of M.
      leprae by ofloxacin and rifampicin before mass treatment can be recommended. The
      complications and side-effects of ofloxacin and rifampicin were of a mild nature
      and both drugs were well tolerated. Moderate to marked clinical improvement was
      noticed in a short period with ofloxacin containing regimens in multibacillary
      leprosy patients. No persisters were detected in any of the 33 specimens (of
      mouse footpads) that had been obtained after treatment for 6 months. Ofloxacin if
      added to the currently used WHO recommended MB-MDT regimen may shorten the
      duration of treatment. Ofloxacin, therefore, may be considered as a suitable
      alternative in suspected/proven rifampicin resistant cases and where rifampicin
      is contraindicated. The results were evaluated on the basis of the clinical
      conditions, mycobactericidal effectiveness, signs of drug toxicity and side
      effects.

PMID- 9656406
TI  - Socio-environmental predictors of soil-transmitted helminthiasis in a rural
      community in Malaysia.
AB  - Soil-transmitted helminthiasis is a common problem in communities with poor socio
      environmental conditions. This study was undertaken to identify important socio
      environmental predictors of soil-transmitted helminthiasis in Bachok, a rural
      community in Kelantan for the development and implementation of an effective
      prevention and control program. Of 363 children randomly sampled, 38.8% were
      infected with soil-transmitted helminthiasis. Risk predictors of soil-transmitted
      helminthiasis found to be significant after adjustment included poor household
      hygiene score and large household size. The probability of being infected was
      0.58 amongst children with both of these risk factors.

PMID- 9656407
TI  - The impact of primary health care intervention on reinfection of soil-transmitted
      helminths in the community.
AB  - A study to evaluate the impact of primary healthy (PCH)care practices on the
      prevention of reinfection of soil-transmitted helminths (STH) was carried out in
      Nakhon Si Thammarat Province, southern Thailand. Fecal samples from the
      inhabitants of Ban Paruhas, the implementing village, and Ban Pungsing, the
      control village, were examined following mass treatment with a three-day regimen
      of albendazole (400 mg). Training of health volunteers, implementation of a
      health education program through village broadcasting system and improvements in
      sanitation including increasing the number of latrines were carried out at Ban
      Paruhas village. After one year of implementation, prevalence and intensity of
      STH in both villages were determined using Kato-Katz's method. Pre- and post
      intervention stool examination results were compared. The overall prevalence of
      STH at post-intervention decreased significantly in both villages, with a greater
      degree of reduction appearing in ascariosis and hookworm infections in the
      village where PHC was implemented.

PMID- 9656408
TI  - Scanning electron microscopic study of microfilaria and the third stage larva of
      Wuchereria bancrofti.
AB  - The surface structures of microfilaria and of the third stage larva of Wuchereria
      bancrofti were studied by scanning electron microscopy. Distinct features were
      observed that could be used for differentiating species of this parasite.
      Specifically, the sheath of microfilariae of W. bancrofti projected beyond the
      head. The head region of the microfilaria was composed of a cephalic cap with
      hook, mouth and amphidial opening, and its cuticle showed annulation. Spines were
      absent at the first transverse annulation, and the tail end showed a slight
      constriction. In the infective stage larva, characters which are used for
      differentiating species, such as the two bubble-like ventro-lateral papillae and
      one dorso-terminal papilla were rather similar to each other in size, but the
      grooves seen around the base were absent. A previously unreported feature of the
      third stage larva of W. bancrofti that was discovered in this study is a
      papilliform process on the left side of the posterior region, between the anus
      and the tail end.

PMID- 9656409
TI  - Estimation of ASO titer as an indicator of streptococcal infection precipitating
      acute adenolymphangitis in brugian lymphatic filariasis.
AB  - Recurrent episodes of acute adenolymphangitis (ADL) are important clinical
      manifestations of lymphatic filariasis which contribute significantly to the
      progression of lymphedema. It is increasingly being recognized that secondary
      bacterial infections play an important role in the etiology of ADL. We examined
      the role of streptococcal infection as a precipitating factor of ADL in brugian
      filariasis, by determining the anti-streptolysin O (ASO) titers and by isolating
      the causative organism wherever possible. The study population consisted of 30
      patients with filariasis related ADL (Group A), 30 patients with chronic filarial
      edema (Group B) and 60 age and sex matched healthy adults (Group C). ASO titer
      was estimated by the latex agglutination method at the time of entry into the
      study, at the 15th day and at 3, 6 and 12 months. ASO titers were persistently
      elevated in 90% of patients in Group A and a portal of entry for bacterial
      infection was detected in all of these patients. In Group B only six patients had
      persistently elevated ASO titers. These patients had grade III lymphedema and
      three of them had monilial infections in the affected limb. In the control group
      none had persistently elevated ASO titers. The elevated ASO titers and the
      detection of a site of entry for bacteria in patients with ADL supports a
      streptococcal etiology for this condition.

PMID- 9656410
TI  - Human infection of Centrocestus caninus in Thailand.
AB  - Examination of fecal samples, collected after treatment with praziquantel, of the
      persons positive with opisthorchioid eggs residing in the northern provinces of
      Thailand, was carried out. Five adults Centrocestus were recovered in one sample
      from Doi Saket, Chiang Mai and one adult was found in another fecal sample from
      Wiang Pa Pao, Chiang Rai. The worms had 26-30 spines arranging in two rows around
      the oral sucker which agreed with the character of C. caninus. This is the first
      record of natural human infection with Centrocestus in Thailand.

PMID- 9656411
TI  - Visceral leishmaniasis with cutaneous ulcer or cutaneous leishmaniasis in Nepal.

PMID- 9656412
TI  - Features of Schistosoma mansoni infection in SCID mice.
AB  - Features of Schistosoma mansoni infection in SCID mice, which lack functional T-
      and B-lymphocytes, were investigated. The retarded development of parasites as
      well as reduction of liver egg recovery in SCID mice was significantly lower than
      those in congenic counterpart C.B-17 mice. Furthermore, the rate of parasite
      recovery from SCID mice with primary infection was always lower than that from
      C.B-17 mice by 20%, showing the innate resistance to S. mansoni infection. SCID
      mice vaccinated with UV-attenuated S. mansoni cercariae did not show protective
      immunity against a homologous challenge infection. The present innate resistance
      exhibited in SCID mice is discussed in relation to cell mediated immunity of
      macrophage activation by IFN-gamma which would not involve T-lymphocytes but is
      initiated by IL-12 and TNF-alpha cytokines. SCID mice may provide novel
      information on the host-parasite relationship in schistosome infections.

PMID- 9656413
TI  - Breeding habitats of Aedes aegypti (L) and Aedes. albopictus (Skuse) in villages
      of Barru, South Sulawesi, Indonesia.
AB  - The breeding habitats of the dengue vector, Aedes aegypti and Aedes albopictus,
      were studied using larval collection method inside and outside houses in 6
      villages of Barru, South Sulawesi, Indonesia from July 1994 to August 1995. Aedes
      aegypti was the dominant species, being abundant indoors especially in the
      coastal areas. Aedes albopictus was breeding primarily in outdoor containers in
      the hill and mountain areas. Earthen jar was the most common breeding habitat of
      Aedes aegypti in all villages surveyed. Drum can was the most common outdoor
      breeding habitat of Aedes albopictus in the hill and mountain areas. The high
      Breteau indices of Aedes aegypti and Aedes albopictus suggests that these species
      may play an important role in the transmission of dengue hemorrhagic fever in
      Barru where epidemics of the fever occur occasionally.

PMID- 9656414
TI  - A field trial with etofenprox (OMS 3002) as a residual insecticide against
      malaria vectors, in Tanjung Bunga district, east Flores, Indonesia.
AB  - An operational trial of Vectron (Etofenprox, OMS 3002) was conducted in East
      Flores Regency, Nusa Tenggara Timur Province. The compound (Etofenprox 10EW) was
      applied as indoor residual spray and as an impregnation treatment for bednets in
      two separate areas. Dosage in both cases was 0.2 g/m2. A third area, designated
      as control, was untreated. In bioassay tests, bamboo surfaces gave 100% mortality
      for 150-160 days post spray, while wooden surfaces and treated bednets both gave
      complete mortality for at least 120 days. Malaria cases monitored by successive
      malariometric surveys showed steady declines in positivity rates, particularly in
      children.

PMID- 9656415
TI  - Laboratory evaluation of the biocontrol potential of Mesocyclops
      thermocyclopoides (Copepoda: Cyclopidae) against mosquito larvae.
AB  - Biocontrol potential of Mesocyclops thermocyclopoides against first instar larvae
      of Anopheles stephensi, Aedes aegypti and Culex quinquefasciatus was studied
      under laboratory conditions. It was found that M. thermocyclopoides had the
      highest predation efficacy against Ae. aegypti followed by An. stephensi and Cx.
      quinquefasciatus. There was a significant reduction in the predation efficacy of
      M. thermocyclopoides against Cx. quinquefasciatus in the presence of alternate
      food (p < 0.01). The cage simulation trial indicated that M. themocyclopoides has
      the potential to control Ae. aegypti breeding effectively in a container type of
      habitat.

PMID- 9656416
TI  - Shelf-life of pre-cooked rice oral rehydration salt packets.
AB  - The shelf-life of pre-cooked rice oral rehydration salts (ORS) at the household
      level was studied in urban Dhaka. To prepare the packets, cooked rice was dried
      and ground to fine powder and the salt ingredients were mixed according to the
      World Health Organization formulation. For each half liter packet, 10 g glucose
      was replaced by 25 g of instant cooked rice powder. The packets were kept in
      different environments for three months among 30 households of varying
      socioeconomic status. At monthly intervals, two packets from each family were
      collected for laboratory tests. Physical characteristics of ORS such as color and
      dispersibility remained the same throughout the three month study period.
      However, in the third month flavor changed slightly. The electrolyte
      concentration of the prepared solution remained the same at the end of the first,
      second and third months. However, progressive but minimal increase in moisture
      content of the packets was noted over the allotted time period. This increase in
      moisture was less when the mixture was packed in double thin layer polythene bags
      as opposed to the single layer bags. In conclusion, the shelf-life of pre-cooked
      rice ORS remains stable at least up to three months when stored at the household
      level. Therefore, pre-cooked rice ORS can be kept at households for future use in
      the event of diarrheal episodes.

PMID- 9656417
TI  - Health behavior, perceptions, practices, and decision making: sub-national and
      socio-demographic differentials in Bangladesh, 1995.
AB  - The study examines health behavior, perceptions, practices, and decision making
      using data from the 1995 Health and Demographic Survey conducted by the
      Bangladesh Bureau of Statistics. Knowledge about causes of diarrhea and food
      contamination were higher than knowledge about causes of nightblindness and worm
      infestation but this knowledge is inadequate. The household's economic condition
      and the respondent's education were found to be positively associated with
      disease knowledge and food contamination; the same is also true for health
      behavior and practices. Sub-national variation in disease knowledge and food
      contamination exists but did not correspond always with the health behavior and
      practices. Decisions regarding treatment of disease were made by the husband and
      wife together in two-thirds of the cases, however, it was not uniform across
      socio-demographic and sub-national categories.

PMID- 9656418
TI  - The relationship between maternal weight gain in pregnancy, hemoglobin level,
      stature, antenatal attendance and low birth weight.
AB  - Low birth weight (birth weight less 2,500 g) remains a major public health
      problem in many communities. Five hundred and twenty-eight (528) consecutive
      singleton maternities delivered at the Armed Forces Hospital Tabuk, northwest
      Saudi Arabia were studied to identify the relationship between prenatal weight
      gain, maternal hemoglobin at delivery, maternal stature, antenatal clinic
      attendance and low birth weight (LBW). Of the total number, 9.5% (50/528) babies
      were of low birth weight, 56% of which were preterm while 44% were term and small
      for gestational age, resembling the pattern observed in developed countries
      rather than developing countries. Mothers who delivered LBW babies gained
      significantly less weight in the 3rd trimester and last 4 weeks of term pregnancy
      when compared with controls who had normal weight babies (NW > or = 2,500 g) who
      were delivered in the study period (t = 4.06, p < 0.0001, t = 3.7, p < 0.001).
      There was no significant difference in the prenatal weight gain in the second
      trimester for the two groups of mothers (p = 0.53). Mothers with LBW babies also
      had significantly lower Body Mass Index (BMI) at onset of pregnancy (t = 3.8, p =
      0.001) and were shorter in height (t = 2.12, p < 0.03). Mothers who delivered
      preterm LBW babies had significantly lower hemoglobin levels at delivery when
      compared with those who had NW deliveries (p < 0.002). There was no difference in
      hemoglobin levels of mothers who had LBW babies at term and those with NW at term
      (p = 0.72). For this community, it is suggested that to reduce the LBW baby rate
      and improve birth weight, anemia must be prevented in pregnancy; attention needs
      to be paid to weight gained in the third trimester and the last 4 weeks of
      pregnancy encouraging antenatal clinic attendance, and improving the nutritional
      status of female children so that optimal height is achieved by the age of
      reproduction.

PMID- 9656419
TI  - Zinc and copper status of thalassemic children.
AB  - We investigated the amount of both zinc and copper in plasma, erythrocytes and
      hair in 11 patients with hemoglobin H disease, 59 patients with beta
      thalassemia/HbE disease and 20 patients with homozygous beta-thalassemia. Plasma
      and hair zinc levels were found to be much lower, but erythrocyte zinc levels
      were higher, in thalassemic patients than in controls. The levels of copper in
      both plasma and erythrocytes were higher in the patients than in the controls.
      The mechanism with respect to the increase of the amount of both zinc and copper
      in erythrocytes was not clear; this result may reflect the impairment of zinc and
      copper utilization in tissues in the pathogenesis of these thalassemic patients.

PMID- 9656420
TI  - Risk factors for traffic accidents in Bangkok Metropolis: a case-reference study.
AB  - It was aimed to study injures from road traffic accidents in Bangkok Metropolis
      and identify patients' characteristics as well as to search for risk factors for
      traffic accidents leading to hospitalization. The study included 346 in-patient
      cases suffering injuries from road traffic accidents in Bangkok Metropolis. The
      patients were recruited during a period of 4 months of the year 1992 from five
      hospitals in various areas of Bangkok which were judged to be representative for
      Bangkok Metropolis. Using the method of case-reference, relative risk could be
      estimated for various exposure factors. Most of the patients drove a motorcycle,
      had their license for only a short period, and drove more than 5 hours a day.
      About one third of the patients were under the influence of alcohol. The traffic
      accident characteristics were that they occurred mainly at night time with the
      peak between 21.00 and 24.00 hours. About 90% of all traffic accidents occurred
      during the rainy season and most of them occurred near to road junctions.
      Reference data was available for some variables and the following risk group
      could be identified: RR (male-age 20-24) = 17.06 (8.8-33.9), RR (single-marital
      status) = 2.25 (1.7-3.1), RR (primary-education) = 6.2 (2.9-12.6), RR (unskilled
      labourer-occupation) = 3.91 (2.7-5.9), RR (salesperson-occupation) = 3.34 (2.2
      5.0).

PMID- 9656421
TI  - Immunologic function in horses after non-specific immunostimulant administration.
AB  - Inactivated Propionibacterium acnes is a biologic response modifier for treatment
      of non-specific respiratory disease in horses. The objectives of this
      investigation were to determine alterations in phagocytic activity, phenotypic
      expression of lymphocyte subpopulations and lymphokine-activated killing cell
      response in healthy young horses. Samples were collected on day 0, 7 and 14 of
      the investigation. Blood samples were obtained via jugular venipuncture and
      pulmonary leukocytes were recovered via bronchoalveolar lavage (BAL).
      Commercially available P. acnes (Eqstim) was administered intravenously on days
      7, 9 and 11 of the investigation. Fever was observed on days 8 and 10, indicating
      immune reaction. Total peripheral blood white cell count was increased (P < 0.05)
      on day 14 after P. acnes administration compared to values on days 0 and 7. Total
      BAL fluid cell count decreased (P < 0.01) on day 14 compared to values on days 0
      and 7, which was characterized by a decrease in total lymphocyte (P < 0.01) and
      macrophage (P < 0.01) counts. The proportion of lymphocytes in BAL fluid
      decreased (P < 0.005) on day 14 compared to values on days 0 and 7, and the
      proportion of macrophages increased (P < 0.005) on day 14 compared to values on
      days 0 and 7. P. acnes administration increased the total (P < 0.05) and
      proportional (P < 0.05) counts of CD4+ T lymphocytes in peripheral blood.
      Bronchoalveolar lavage fluid proportion of CD4+ (P < 0.05), CD5+ (P < 0.001) and
      MHC II (P < 0.05) lymphocytes increased on day 14 after P. acnes administration
      compared to values on days 0 and 7. Nonopsonized phagocytic activity in
      peripheral blood increased (P < 0.0005) on day 14 after P. acnes administration
      compared to values on days 0 and 7. Lymphokine-activated killing cell activity in
      peripheral blood and BAL fluid leukocytes was enhanced (P < 0.005) on day 14
      after P. acnes administration compared to values on days 0 and 7. Serum IgG and
      IgM concentrations were within laboratory reference values and were not altered
      by administration of P. acnes. This investigation demonstrated immunostimulant
      and immunomodulatory properties of P. acnes, characterized by increased CD4+ T
      lymphocyte expression and LAK activity in peripheral blood and BAL fluid,
      increased nonopsonized phagocytosis in peripheral blood leukocytes and decreased
      pulmonary cellularity.

PMID- 9656422
TI  - Analyses of leucocytes in blood and lymphoid tissues from mink infected with
      Aleutian mink disease parvovirus (AMDV).
AB  - Mink were infected with Aleutian Mink Disease Parvovirus (AMDV) and sacrificed at
      monthly intervals after infection. During this time humoral immune responses and
      leucocyte numbers in blood, mesenteric lymph node, spleen and thymus were
      monitored. Serum hypergammaglobulinaemia was observed together with elevated
      antibody responses to AMDV NS1 and VP1/2 proteins. In blood, a highly significant
      increase in CD8+ lymphocytes was observed. However, (presumed)CD4+ cells defined
      as CD3+CD8- cells, and B lymphocytes remained relatively constant throughout the
      study. The (presumed)CD4+/CD8+ ratio decreased significantly from greater than 2
      to less than 0.5 and MHC-II+ blood leucocytes increased significantly during
      infection, a large proportion of these being CD8+. Similar changes were observed
      in the mesenteric lymph node and spleen. Immunohistology of lymph nodes showed a
      massive expansion of the paracortical area due to increased numbers of CD8+
      cells. The staining intensity of B lymphocytes in lymph nodes with a CD79a
      reactive monoclonal antibody was decreased in the late infection, indicating a
      possible greater number of plasma cells. Thymic involution was observed during
      the AMDV infection, although relative increases in CD3high (presumed)CD4+ and
      CD3highCD8+ single positive cells were observed. These increases were countered
      by a corresponding reduction in the CD3low(presumed)CD4+CD8+ double positive cell
      population. Immunohistology of the thymus in normal mink showed that most of the
      matured CD3+ T cells were present in the inner medulla, while only few CD3+ cells
      could be found in the outer cortex. In severely infected mink the thymic
      structural organisation vanished, and CD3+ cells were found throughout the organ.

PMID- 9656423
TI  - Thymic alterations in feline GM1 gangliosidosis.
AB  - GM1 gangliosidosis is an inherited metabolic disease characterized by progressive
      neurological deterioration with premature death seen in children and numerous
      animals, including cats. We have observed that thymuses from affected cats
      greater than seven months of age (GM1 mutant cats) show marked thymic reduction
      compared to age-matched normal cats. The studies reported here were done to
      describe alterations in the thymus prior to (less then 90 days of age) and during
      the development of mild (90 to 210 days of age) to severe (greater than 210 days
      of age) progressive neurologic disease and to explore the pathogenesis of the
      thymic abnormality. Although histologic examination of the thymus from GM1
      affected cats less than 210 days of age showed no significant differences from
      age-matched control cats, thymuses from GM1 mutant cats greater than 210 days of
      age were significantly reduced in size (approximately 3-fold). Histologic
      sections of lymph nodes, adrenal glands, and spleens from GM1 gangliosidosis
      affected cats showed no significant differences. Flow cytometric analyses showed
      a marked decrease in the percentage of immature CD4+CD8+ thymocytes (p < 0.001)
      and significantly increased CD4-CD8+ cells (p < 0.01) in GM1 mutant cats greater
      than 210 days of age when compared to normal age matched cats. Co-labelling with
      CD4, CD8, and CD5 indicated an increase in the percentage of GM1 mutant cat
      thymocytes at this age which were CD5high, suggesting the presence of more mature
      cells. Cytometric analyses of subpopulations of peripheral lymphocytes indicated
      an increase in CD4-CD8+ cells (p < 0.05) with concurrent decreases in CD4+CD8-
      and CD4-CD8- cells (which were not significant). Similar analyses of thymocyte
      and lymphocyte subpopulations from cats < 210 days of age showed no significant
      differences between GM1 mutant and normal cells. GM1 mutant cats at all ages had
      increased surface binding of Cholera toxin B on thymocytes, indicating increased
      surface GM1 ganglioside expression. Increases were highly significant in GM1
      mutant cats greater than 210 days of age. In situ labelling for apoptosis was
      increased in GM1 mutant cats between 90 to 200 days of age when thymic masses
      were within normal limits. In GM1 mutant cats over 200 days of age, decreased
      labelling was observed when thymic mass was reduced and the CD4+CD8+
      subpopulation, known to be very susceptible to apoptosis, was significantly
      decreased. These data describe premature thymic involution in feline GM1
      gangliosidosis and suggest that increased surface GM1 gangliosides alters
      thymocyte development in these cats.

PMID- 9656424
TI  - Role of the humoral immune system in Salmonella enteritidis phage type four
      infection in chickens.
AB  - The role of avian humoral immunity in the clearance of S. enteritidis was
      evaluated through bursectomy. After oral inoculation of bursectomized and sham
      treated chickens with S. enteritidis, faecal excretion of S. enteritidis was
      examined. Organs were collected weekly until six weeks post-inoculation (pi) for
      bacteriological enumeration. Antibody isotypes in serum and bile were quantified
      by ELISA. Faecal excretion of S. enteritidis was significantly lower in controls
      from 13 days pi. Numbers of S. enteritidis in caeca from controls were
      significantly decreased from three weeks pi. Numbers of S. enteritidis were
      significantly decreased at two weeks pi in the spleen and the liver and at six
      weeks pi in the liver. Antibodies to S. enteritidis peaked at two weeks pi in
      controls and were absent in bursectomized chickens. These findings indicate that
      elimination of S. enteritidis partly depends on humoral immunity. The intestinal
      humoral response appeared more effective than the systemic humoral response for
      elimination of S. enteritidis.

PMID- 9656425
TI  - Isolation of rainbow trout neutrophils with an anti-granulocyte monoclonal
      antibody.
AB  - A magnetic cell sorting system has been optimised for the purification of rainbow
      trout neutrophils using a monoclonal antibody (E3D9) raised against Atlantic
      salmon neutrophils. The purified neutrophils have good viability (85%) and purity
      (approximately 92%), and were functional in respiratory burst and migration
      assays. The isolated neutrophils responded rapidly to PMA stimulation, producing
      levels of superoxide anion (4.85 nmols superoxide min-1/10(6) cells)
      approximately twice as high as macrophages from the same species. In the
      migration assay, there was a four-fold increase in migrating cells using the
      purified neutrophils compared with unfractionated blood leucocytes, and a
      relatively high neutrophil migratory activity was seen in the absence of serum.

PMID- 9656426
TI  - Cloning and sequencing of cDNA encoding bovine macrophage colony-stimulating
      factor (bM-CSF) and expression of recombinant bM-CSF using baculovirus.
AB  - The cDNAs encoding bovine macrophage colony-stimulating factors alpha and beta (M
      CSF alpha and M-CSF beta) were cloned and recombinant bovine M-CSF alpha (rbM-CSF
      beta) in its dimeric form was expressed by using a recombinant baculovirus/insect
      cell system. The predicted amino acid sequence of rbM-CSF alpha and rbM-CSF beta
      shared 83.3 and 75.9% (alpha), 75.3 and 65.9% (beta) similarity with the sequence
      for human and murine M-CSFs, respectively. The biological activity of rbM-CSF
      beta was confirmed by the colony-forming assay using mouse bone marrow cells. SDS
      PAGE under a reducing condition showed that the molecular weight of rbM-CSF beta
      was approximately 34 kDa. On the other hand, Western blot analysis under a non
      reducing condition revealed that this rbM-CSF beta was secreted in dimeric form
      into the cell supernatant.

PMID- 9656427
TI  - Analysis of the immunological cross reactivities of 213 well characterized
      monoclonal antibodies with specificities against various leucocyte surface
      antigens of human and 11 animal species.
AB  - 213 Monoclonal antibodies (mAbs) raised against leucocyte surface antigens from
      human and 11 animal species were analyzed for reactivities against leucocytes
      from human and 15 different animal species. We found 77 mAbs (36%) to cross
      react. Altogether, 217 cross reactions were registered out of 3195 possible
      combinations (7%). Most of the cross reacting mAbs had integrin or MHC class II
      specificities. This study defined cross reactions on the following markers: CD1a,
      1c, 2, 4, 5, 8, 9, 11a, 11b, 14, 18, 20, 21, 23, 29, 31, 41, 43, 44, 45, 45R, 46,
      49, 61, 62L, TCR gamma/delta, BCR, Thy-1, MHC class I and MHC class II, Swine-WC7
      and Cattle-WC1. In order to characterize the molecular weight (MW) of the
      corresponding cross reacting antigens, selected mAbs were used to
      immunoprecipitate the antigens. The MW's of the analyzed precipitated antigens
      were in good agreement with the MWs of the homologous antigens. The followed
      strategy was found to be efficient and economical in defining new leucocyte
      antigen reactive mAbs.

PMID- 9656428
TI  - Characterization of two dog IgE-specific antibodies elicited by different
      recombinant fragments of the epsilon chain in hens.
AB  - Two recombinant [His]6-tagged fragments of the canine immunoglobulin E (IgE)
      heavy chain (second domain: IgEf2 and third and fourth domains: IgEf3/4) were
      cloned, expressed in Escherichia coli (E. coli) as [His]6-tagged proteins, and
      affinity-purified over nickel-nitrilotriacetic acid columns. The recombinant
      proteins were used to immunize hens. The raised and affinity-purified chicken
      antibodies (Ab) isolated from egg yolk exhibited specific binding to the
      respective recombinant canine IgE fragment (IgEf) on immunoblots and displayed
      high titers against the IgEf in ELISA. Immunoblotting of canine serum separated
      by PAGE under native conditions with the IgEf2- and IgEf3/4-specific Ab resulted
      in staining of a protein of approximately 180 kilodaltons (kD). The IgEf3/4
      specific Ab further recognized an 80 kD protein in IgEf3/4-specific Ab affinity
      enriched dog serum separated under denaturing conditions. In an ELISA for the
      detection of antigen-specific IgE in dog serum, reduced binding of the IgEf
      specific Ab was observed after heat treatment of the dog serum. The reactivity of
      both of the raised chicken Ab was only present in postimmune reagents and could
      only be inhibited by preincubation with the IgEf used for immunization and not
      with dog immunoglobulin G, E. coli extract, or with a nonrelevant recombinant
      [His]6-tagged protein. In immunohistochemistry, the IgEf3/4-specific Ab
      specifically recognized cells in paraffin-embedded tissue sections of lymph
      nodes. Furthermore, both of the IgEf-specific Ab elicited positive immediate type
      1 skin reactions in dogs. Semiquantitative assessment of total serum IgE in dogs
      was developed using IgEf2-specific Ab as coating reagent and the biotinylated
      IgEf3/4-specific Ab as developing Ab in ELISA. In conclusion, both IgEf-specific
      Ab recognize native dog IgE with the advantages that they are directed against
      different and known constant domains of the IgE molecule, and that they can be
      used for immunohistochemistry on paraffin-embedded tissue. The two dog IgE
      specific Ab could initiate clinical research on the involvement of immediate-type
      hypersensitivity reactions in dogs.

PMID- 9656429
TI  - Apoptotic fraction in lymphoid tissue of FIV-infected SPF cats.
AB  - In the present study the apoptotic fraction has been investigated in peripheral
      blood mononuclear cells (PBMCs) and in lymphoid tissue of six clinically
      asymptomatic serologically positive specific pathogen free (SPF) FIV-infected
      cats with a decline in peripheral blood CD4+ lymphocytes, compared to five FIV-
      SPF controls. Apoptosis in PBMCs was scored in relation to cell cycle phases
      judged by the integrating cytometric measure of DNA content with 3H-thymidine and
      3H-leucine incorporation. Apoptosis in lymphoid tissue was revealed with the
      ApopTag-peroxidase kit, quantified by image analysis and expressed as apoptotic
      index (number of apoptosis per 100 cells). The high percentage of apoptotic death
      in lymphocytes from FIV+ cats was chronologically related to the entrance of
      cells in the S phase of the cell cycle (p < 0.0001). No difference in the
      apoptotic index was revealed comparing the follicular, cortical + paracortical
      and medullary compartments in lymph nodes of FIV+ and FIV- cats. In each group of
      cats a similar pattern of apoptosis expression was revealed in lymph nodes:
      significantly higher in follicular vs. both cortical + paracortical and medullary
      compartments (p < 0.001). In the thymus a significant increase in apoptotic index
      was revealed in the cortical compartment of the FIV+ cats compared to FIV- (p <
      0.001), while in the spleen both the red and white pulp expressed a higher value
      in FIV+ cats compared to FIV-(p < 0.05) and the former showed a pattern of
      expression as follows: in the red pulp significantly higher than in the white
      pulp (p < 0.001). This investigation suggests that the priming signals for
      apoptosis in FIV infection parallels the S phase of the cell cycle and peripheral
      blood changes could follow both thymic and splenic modifications in apoptotic
      expression.

PMID- 9656430
TI  - Modulation of interleukin production by ascorbic acid.
AB  - We studied the influence of ascorbate (vitamin C) on peripheral blood mononuclear
      cells (PBMC) of pigs with hereditary deficiency in ascorbate synthesis. Groups of
      animals were depleted of, or supplemented with dietary ascorbate for up to 5
      weeks. B lymphocytes and T lymphocyte subsets differed in the two experimental
      groups only marginally and transiently as determined by analysis of cell surface
      markers. The proliferative response of PBMC to B and T lymphocyte mitogens was
      lower in depleted as compared to supplemented animals. Interleukin (IL)-2 and IL
      6 were determined by bioassays and were secreted within few hours after mitogenic
      activation of PBMC which contained normal physiological concentrations of
      ascorbate. IL-2 production peaked at about 24 h of in vitro culture after Con A
      activation, but it lasted for 2-3 days after PWM activation. The production of IL
      2 and IL-6 were compared during systemic depletion and supplementation with
      ascorbate. Depleted PBMC produced IL-2 which accumulated in cultures instead of
      being rapidly consumed by IL-2 dependent cell growth. This suggests that cellular
      ascorbate influences the production of IL-2. Secretion of IL-6 by mitogen
      activated PBMC was also affected by prolonged dietary ascorbate depletion. The
      results suggest that ascorbate levels exert an early effect on immune homeostasis
      via reactive oxygen intermediates (ROI)-dependent expression of interleukin
      genes, since the transcription factor NF-kappa B is sensitive to ROI and
      regulates the expression of interleukin genes.

PMID- 9656431
TI  - Influence of the sequence of administration of beta-glucans and a Vibrio damsela
      vaccine on the immune response of turbot (Scophthalmus maximus L.).
AB  - Yeast (Saccharomyces cerevisae) beta-1,3 glucans were used as adjuvant in a
      Vibrio damsela vaccine for turbot (Scophthalmus maximus L.). Turbot were injected
      with the adjuvant prior, at the same time and after the vaccine. Several immune
      parameters (index and rate of phagocytosis, passive haemolytic plaque numbers,
      and agglutinating antibody titers) were determined at different times
      postinoculation. The highest activity of all the immune parameters was obtained
      when glucans were injected after the bacterin. It is concluded that the sequence
      of glucan administration is critical when used as a vaccine adjuvant.

PMID- 9656432
TI  - Benzo[a]pyrene-induced hypocellularity of the pronephros in tilapia (Oreochromis
      niloticus) is accompanied by alterations in stromal and parenchymal cells and by
      enhanced immune cell apoptosis.
AB  - Numerous reports indicate that carcinogenic polycyclic aromatic hydrocarbons
      (PAH) are mammalian immunotoxicants. These environmental contaminants are widely
      distributed in both freshwater and costal marine ecosystems where they have been
      found to bioaccumulate in aquatic species, yet limited information exists
      regarding potential adverse effects of specific PAH on fish immune function. In
      the present report, Oreochromis niloticus fish (tilapia) were exposed by
      intraperitoneal injection to 5, 25, or 50 mg/kg of the PAH, benzo[a]pyrene
      (B[a]P). Histopathologic evaluation of the primary hematopoietic compartment of
      fish, the pronephros, demonstrated increased vacuolation of both stromal and
      parenchymal cells, reduction of lymphoid elements, and immune cell apoptosis.
      Total pronephros cell counts were diminished in a dose-dependent manner by the
      chemical exposure. The oxidative metabolic burst in phorbol myristate acetate
      (PMA)-simulated macrophages isolated from the pronephros was significantly
      inhibited by B[a]P, but only at the highest dose level employed. The phagocytic
      capacity of pronephros macrophages was not altered by the chemical treatment.

PMID- 9656433
TI  - Fluorescein isothiocyanate staining and characterization of avian heterophils.
AB  - Fluorescein isothiocyanate (FITC) was found to stain cytoplasmic granules of
      avian heterophilgranulocytes. In tissue sections, the fluorescent granulocytes
      were predominantly distributed adjacent to trabecular bones. The fluorescein
      stained granulocytes were abundant in synovial fluids of chickens with synovitis.
      A significant correlation was observed in the percent of fluorescein labeled
      granulocytes in blood smears and the percent of heterophils determined using an
      automated counting method, in unstained blood from normal and Escherichia coli
      infected turkeys. The fluorescein-binding heterophils purified from chickens
      showed a time dependent increases in the oxidation of 2',7'-dichlorofluorescin
      diacetate (DCF-DA) and the reduction of nitroblue tetrazolium (NBT) which were
      indicative of changes in oxidative burst in response to phorbol 12-myristate 13
      acetate (PMA), Salmonella typhimurium lipopolysaccharide (LPS), and zymosan A
      (ZA). These heterophil-activating agents, also, caused significant degranulation
      at 16 h post-treatment, as indicated by the loss fluorescence. There were
      microscopically visible alterations in the cell shapes and a decrease in the
      density of granules due to treatment with LPS, PMA or ZA. In addition, these
      cells also showed phagocytic response which was evident at 30 min of incubation
      with fluorescent latex particles. Both chicken and turkey heterophils produced
      interleukin-6 in vitro at 24 h in response to LPS but not to PMA, FMLP or ZA. The
      chicken heterophils showed spontaneous production of matrix metalloproteinases
      (MMP) which was significantly enhanced by treatment with LPS, PMA, and ZA;
      however, LPS appeared to be most effective in inducing MMP production. These
      results demonstrate that the functions of heterophils can be differentially
      regulated by different activating agents and the fluorescein binding property of
      these cells may be useful for their histochemical identification.

PMID- 9656434
TI  - Proceedings of the First International Symposium on Cytokines and the Type I,
      Type II Paradigm. Cairns, Australia, Oct. 25-30, 1996.

PMID- 9656435
TI  - Comparison of the unique characteristics of the immune system in different
      species of mammals.
AB  - The current interpretation of how cytokines regulate immune responses is based
      largely on studies conducted in humans and rodents. As summarized here,
      comparative studies have revealed significant differences in the composition of
      the immune system in other species. The difference noted emphasize that it will
      not be possible to fully understand the role of cytokines in immune regulation
      without comparative studies that include analysis of cytokine function in
      additional species.

PMID- 9656436
TI  - CD40 ligand-dependent signaling of bovine B lymphocyte development and
      differentiation.
AB  - The role of IFN-gamma in B cell differentiation in cattle has not been completely
      elucidated. We have previously investigated the role of IFN- in the control of
      antibody production by bovine B cells using anti-bovine IgM antibody in the solid
      phase as a source of costimulation. Using this mimic of a T1-2 antigen, we
      demonstrated that IFN-gamma can enhance the production of IgG2 but not IgG1 from
      sIgM+ cells. The positive effects of IFN-gamma were enhanced by co-addition to
      cultures of rboIL-2. Under these activation conditions, the frequency of cells
      expressing mRNA for the IgG2 heavy chain also increased at least two-fold. In
      these studies, we investigated the role of IFN-gamma in antibody expression under
      T-dependent (TD) activation conditions using mouse fibroblasts transfected with
      boCD40L as a surrogate T cell. Under TD conditions, IFN-gamma had less dramatic
      effects on the production of IgG2 with IgM predominating in the cultures.
      Interestingly, the production of IgA was modestly enhanced with little effect on
      the production of IgG1 above baseline levels obtained with medium alone. In
      comparison to results with T1-2 conditions of activation, IL-2 did not increase
      total amounts of antibody above two-fold. Our results suggest that TH1 cells in
      cattle may be limited in their ability to provide B cell help to levels
      obtainable in a TH2 cytokine microenvironment due to the effects of IFN-gamma on
      bovine B cells co-activated via CD40.

PMID- 9656437
TI  - Regulation of bovine interleukin-1 receptors.
AB  - Interleukin-1 is a key player in inflammation and the immune response. The
      interleukin-1 family consists of three ligands (IL-1 alpha, IL-1 beta, and the IL
      1 receptor antagonist) and two receptors (IL-1RI and IL-1RII). Previous studies
      suggest a dynamic relationship among these receptors and ligands that regulates
      the magnitude and extent of IL-1 mediated activities. Our laboratory has cloned
      and sequenced the bovine type I and II interleukin-1 receptors, and has begun to
      investigate their regulation in bovine leukocytes in vitro and in vivo. IL-1RI
      and IL-1RII mRNA levels were upregulated in vitro by various mediators, including
      dexamethasone, rBoIL-4, rBoGM-CSF, and rHuTNF alpha. Conversely, IL-1RI mRNA
      levels were down-regulated by IFN-gamma. An in vivo study indicated that IL-1RII
      mRNA levels increased earlier than IL-1RI mRNA levels in dexamethasone-treated
      cattle. These findings suggest that early upregulation of IL-1RII, which is a
      decoy receptor, may be part of the anti-inflammatory action of glucocorticoids.
      Our investigations suggest that anti-inflammatory agents increase expression of
      the biologically inactive IL-1RII, as compared with the biologically active IL
      1RI, in bovine leukocytes.

PMID- 9656438
TI  - Mechanisms of cytokine signal transduction: IL-2, IL-4 and prolactin as
      hematopoietin receptor models.
AB  - Cytokines, hormones and hematopoietic growth factors transduce biological signals
      across the cell membrane via a highly conserved family of single membrane
      spanning receptors. The intracellular signal transducing machinery responsible
      for mediating these responses has remained largely unknown. However, recent
      identification of a homologous class of tyrosine kinases, Janus Kinases (JAKs),
      and a related family of transcription factors, signal transducers and activators
      of transcription (STATs), has shed new light on the molecular mechanisms
      responsible for mediating hematopoietin signaling and immune response. Current
      research efforts within the field of cytokine signaling have now shifted to
      understanding how these molecules are activated by hematopoietic receptors,
      positively and negatively regulated by kinases and phosphatases, and how they
      impact on gene transcription to ultimately coordinate cell homeostasis,
      proliferation and differentiation. This article will review some of our results
      identifying the involvement of JAKs, STATs, and secondary effector molecules
      activated following engagement of hematopoietic receptors for IL-2, IL-4, and
      prolactin. Here, we provide evidence for the ingenious ability of cytokine
      receptors to selectively recruit and activate these proteins among a repertoire
      of possible alternative biochemical messengers as a means to affect unique and
      general cell responses.

PMID- 9656439
TI  - Helper T cell subsets: heterogeneity, functions and development.
AB  - The discovery that the nature of cytokine production by CD4+ T lymphocytes could
      drastically alter an immune response led to the categorization of distinct helper
      T cell subsets, most notably Th1 and Th2. Recent evidence suggests that such
      helper responses are actually quite heterogeneous and ultimately, the course of
      an immune response depends upon the predominance of particular cytokines. While
      the factors leading to the production of individual cytokines are not completely
      defined, it is clear that the nature and dose of antigen, location of antigen
      challenge, and genetic composition of the individual all play a role in the
      process. Elucidating the cellular and molecular pathways responsible for helper T
      cell differentiation will ultimately permit the manipulation of immune responses
      to pathogens, as well as the development of novel vaccine strategies.

PMID- 9656440
TI  - Bovine type 1 and type 2 responses.
AB  - The Th1/Th2 paradigm has provided a useful framework for understanding the
      observed bias in immune responses that are often dominated by either cell
      mediated or humoral responses, and for devising therapeutic strategies to
      stimulate T cell- or antibody-mediated immunity. However this paradigm is an
      oversimplification of a much more complex immunoregulatory network. Studies with
      bovine Th cell clones and immunoregulatory cytokines support this viewpoint. This
      paper highlights the progress that has been made in defining type 1 and type 2
      responses in cattle. Evidence is presented for the presence of different subtypes
      of antigen-specific Th cell clones of cattle which constitute a spectrum of cell
      phenotypes, and for cytokine-mediated regulation of Th cell responses that
      differs from that observed in mice. The majority of over 60 parasite antigen
      specific Th cell clones coexpress IL-4 and IFN-gamma, and polarized cytokine
      profiles were rarely observed. Furthermore, IL-2 and IL-10 expression was not
      restricted to IFN-gamma or IL-4-producing cells, respectively. This lack of
      coordinate regulation of "Th1" and "Th2" cytokines strengthens the emerging
      viewpoint that Th1 and Th2 responses, per se, do not typify the immune response
      to most pathogens. In addition, we provide evidence that major regulatory
      cytokines, IL-4, IL-10, and IL-12, do not selectively exert their negative (IL-4
      and IL-10) or positive (IL-12) effects on Th1-like cells.

PMID- 9656442
TI  - Influence of IL-12 on interferon-gamma production by bovine leucocyte subsets in
      response to bovine respiratory syncytial virus.
AB  - The cytokine IL-12 is a key molecule in the regulation of CD4+ T cell development
      and specifically potentiates the development of T helper 1 responses in mouse and
      man. However the biological effects mediated by bovine IL-12 have not been
      defined in cattle. To produce the expression of the two mature proteins a
      polyprotein approach was used. This system is employed by positive strand viruses
      and encodes both products from a single open reading frame (ORF). The 2A region
      of foot-and-mouth disease virus (FMDV) encodes a site that appears to undergo
      auto-cleavage. Here the 2A was flanked by sequences encoding the p35 and p40
      polypeptides of the heterodimeric cytokine to mediate their cleavage. Formation
      of the correct heterodimeric structure is an absolute requirement for IL-12
      biologic activity. Using bovine respiratory syncytial virus (BRSV) and ovalbumin
      (OVA) we studied the effects of IL-12 on the responses of peripheral blood
      mononuclear cells (PBMC) to these antigens, in vitro. The presence of IL-12
      markedly influenced the level of IFNg secreted by these cells, and although IL-12
      induced IFNg production in the absence of antigenic stimulation, IFNg production
      was accelerated and augmented in response to IL-12 and antigen. Analysis of the T
      cell subsets by flow cytometry showed that CD4+ T cells comprised the largest
      contributors to IFNg production. The WC1 + gd T cells did not appear to
      contribute to the production of IFNg.

PMID- 9656441
TI  - Interleukin-12 enhances the virus-specific interferon gamma response of pigs to
      an inactivated pseudorabies virus vaccine.
AB  - Cell-mediated immunity is a major component of the host defense system against
      viral infections. Since interleukin (IL)-12 has been shown to be a potent
      stimulus for the in vivo generation of interferon-gamma (IFN-gamma)-producing T
      cells (i.e. Th-1 cells) in laboratory animals, we evaluated the effect of IL-12
      on the cellular immune response of pigs to vaccination against pseudorabies virus
      (PrV), a herpesvirus of swine. The magnitude of the cellular immune response was
      measured by IFN-gamma ELISPOT analysis of peripheral blood mononuclear cells
      (PBMC) from pigs which had been immunized twice, at 2-week intervals, with
      either, modified live virus (MLV) alone or with a commercial inactivated PrV
      vaccine with or without the coadministration of human recombinant IL-12 (HrIL
      12). No significant differences in the titer of virus-neutralizing antibodies or
      in the intensity of the virus-specific lymphoproliferative response among the
      different treatment groups was observed. However, the number of virus-specific
      IFN-gamma-producing cells among PBMC isolated from animals receiving the MLV
      vaccine was on average 3.5 times more than animals immunized with the inactivated
      vaccine (P = 0.01). Administration of the inactivated vaccine and IL-12 induced a
      two-fold higher frequency of virus-specific IFN-gamma-producing cells from that
      induced by the inactivated vaccine alone (P < 0.05). Despite this enhancement,
      the level of protection from lethal PrV challenge provided by the inactivated
      vaccine in combination with IL-12 was the same as that induced by the inactivated
      vaccine alone. Both of these vaccination regimes provided significantly lower
      levels of protection than those afforded by the MLV vaccine. This study
      demonstrates that an inactivated PrV vaccine is a poor inducer of virus-specific
      IFN-gamma-producing cells and that this response can be enhanced by
      administration of exogenous IL-12. The data provides evidence of a dichotomy in
      the humoral and cellular immune responses of pigs to a viral antigen and implies
      the existence of a Th-1/Th-2 type regulation of the anti-viral immune response in
      pigs.

PMID- 9656443
TI  - Measurement of feline cytokine gene expression by quantitative-competitive RT
      PCR.
AB  - We have developed a method to quantitate feline cytokine gene expression using
      competitive RT-PCR. Feline cytokine specific primers were developed that
      encompass an intron, thus allowing differentiation of cDNA vs. genomic DNA
      amplification products. The PCR products of the primers were verified by
      sequencing and Southern blot analysis. For quantitation, a non-homologous RNA
      competitor was created for each cytokine of interest. The competitor was designed
      to yield an RT-PCR product 10-20% larger than the native sequence, thereby
      allowing differentiation of the two products by electrophoresis on an agarose
      gel. Both competitor and native sequences used the same primer sequences for RT
      (oligo dT) and PCR (cytokine specific). The amplification efficiency of the
      competitor and native sequence was shown to be identical which allowed comparison
      at any point during the amplification, including the plateau phase. The quantity
      of starting cytokine mRNA was determined by interpolation from a standard curve.
      As little as 1 microgram of total cellular RNA was required per cytokine
      determination. The assay can routinely quantify as few as 1000 copies of template
      and spans a range of up to 4 log.

PMID- 9656444
TI  - Listeria monocytogenes and Serratia marcescens infections as models for Th1/Th2
      immunity in laboratory cats.
AB  - Five species of bacteria known to be naturally-occurring pathogens of cats were
      screened for their ability to grow in feline macrophages in vitro, and to induce
      antibodies and delayed type hypersensitivity (DTH) responses in vivo. Two of
      these organisms, L. monocytogenes and S. marcescens, were selected for further
      study based on clear-cut differences in their in vitro and in vivo behavior.
      Listeria was macrophage tropic, induced DTH, and evoked poor antibody responses
      post-recovery, whereas Serratia remained extracellular, did not induce a DTH
      reaction, and produced high titer of antibodies. Young specific pathogen free
      cats were then inoculated subcutaneously into the drainage areas of the right and
      left popliteal and auricular lymph nodes with either L. monocytogenes or S.
      marcescens. Each of the four lymph nodes were then removed in sequence over a two
      week period, weighed, cultured for viable bacteria, and RNA extracted for Th1/Th2
      cytokine mRNA quantitation. Antibody responses and delayed type hypersensitivity
      responses were also measured. Identical to pilot studies, cats infected with
      Serratia developed very high levels of antibody compared to Listeria infected
      cats but no DTH, while Listeria infected cats produced negligible or low titers
      of antibodies and strong DTH. Immunity to Listeria occurred around 168 h post
      infection as evidenced by the disappearance of living bacteria from the nodes,
      while immunity to Serratia took over 264 h. Pronounced lymph node hyperplasia
      occurred in both infections, but persisted longer for Serratia. Enlargement of
      Serratia infected nodes was associated with marked follicular, primary and
      secondary germinal center and medullary hyperplasia. Germinal center formation in
      Listeria stimulated nodes was much less intense and dense accumulations of
      macrophages dissected between follicles downward from the subcapsular sinuses.
      Although functional and histologic studies showed a clear-cut cell-mediated vs.
      humoral response in the respective Listeria and Serratia infections, preferential
      cytokine mRNA upregulation was observed for only two of the five major Th1/Th2
      cytokines measured. Interferon-gamma, a Th1 cytokine, was much more elevated in
      the Listeria stimulated nodes, but TNF-alpha (also a Th1 cytokine) was more
      elevated in Serratia infected nodes. Interleukin-12, an important Th1 cytokine,
      was elevated to equal levels in both infections as were the Th2 cytokines IL-4
      and IL-10.

PMID- 9656445
TI  - Type 1 and type 2 cytokines in antiviral defense.
AB  - Ectromelia virus (EV) is a natural mouse pathogen that causes a generalized
      infection termed mousepox, which, in the genetically resistant C57BL/6 (B6)
      mouse, is an inapparent disease. In contrast, BALB/c and A strain mice are highly
      susceptible; one infectious virus particle can result in 100% mortality. The
      contribution of cytokines in the induction of protective immune responses and
      recovery from infection with EV in B6, BALB/c and A strain mice have been. In the
      spleen and lymph node (LN) of resistant B6 mice, IL-2, IFN-gamma and TNF-alpha
      were induced rapidly with large numbers of cells producing these cytokines. All
      three cytokines were virtually absent in BALB/c and A strain mice. No significant
      differences were found in the numbers of IL-4 producing cells in the spleen or LN
      of both resistant and susceptible mice. IFN-gamma-producing cells were detected
      in the spleen but not in the lymph node whereas IL-2-producing cells were
      detected only in the lymph node of B6 mice. Despite significant increases in the
      IFN-gamma mRNA levels in the LN of B6 mice, no protein was detected by
      immunocytochemistry. The mRNA levels of IL-2, TNF-alpha and IL-12 were also
      rapidly upregulated in LN of B6 mice. The rapid induction of type I cytokines
      strongly correlated with a potent antiviral CTL response in B6 mice. The absence
      of these cytokines also correlated with a complete absence or delayed induction
      of CTL responses to EV in both the BALB/c and A strain mice. IFN-gamma gene knock
      out mice on a B6 background were as susceptible to EV as the BALB/c and A strain
      mice.

PMID- 9656446
TI  - Effect of GM-CSF on HIV-1 replication in monocytes/macrophages in vivo and in
      vitro: a review.
AB  - Cells of macrophage lineage constitute the main cellular target of Human
      Immunodeficiency Virus type 1 (HIV-1). Replication of HIV-1 in
      monocyte/macrophages is generally augmented by factors promoting their
      differentiation. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a
      key regular of the differentiation of cells of macrophage lineage. The effects of
      GM-CSF on HIV-1 replication in vitro are still controversial. Most of the
      published studies suggest that GM-CSF upregulates HIV-1 expression in both
      primary cultured macrophages and promonocytic cell lines. There have also been
      reports demonstrating that GM-CSF does not affect HIV-1 replication in cells of
      macrophage lineage or that GM-CSF can actually suppress HIV-1 expression. In
      vivo, GM-CSF administrated to HIV-positive patients at any stage of disease,
      without any antiretroviral therapy, appears to increase HIV-1 activity. The
      possible mechanism by which GM-CSF might affect HIV-1 replication in macrophages
      remains unclear.

PMID- 9656447
TI  - Bystander stimulation of T cells in vivo by cytokines.
AB  - Immune responses to infectious agents, especially viruses, are often associated
      with extensive proliferation of T cells and transient enlargement of the lymphoid
      tissues. Since the precursor frequency of T cells for specific antigen is low,
      the bulk of the T cells proliferating in the primary response are presumably
      stimulated via non-antigen-specific mechanisms, e.g. via cytokines elicited by
      the infectious agent concerned. Such 'bystander' stimulation of T cells occurs in
      mice injected with agents that elicit production of type I interferon (IFN I).
      Induction of IFN I in vivo causes marked stimulation of the CD44hi subset of CD8+
      T cells and is prominent after injection of live viruses or products of bacteria
      such as lipopolysaccharide. Cytokines elicited by infectious agents may act as
      adjuvants during the primary response and could serve to boost the survival of
      long-lived memory cells.

PMID- 9656448
TI  - Cytokine adjuvants: lessons from the past--guidelines for the future?
AB  - Formulation of vaccines has for the most part relied on simple adjuvants which
      are able to enhance the immune response to the immunogen. Cytokines are an
      attractive alternative to conventional preparations, and have been tested in a
      number of different systems. However, experience has indicated that there are a
      number of guidelines that must be followed. The dose of cytokine administered is
      critical for optimal effect. Too little will have no effect, and too much will
      have undesirable side effects. For instance, at high doses IL-2 can induce
      autoimmune disease and interferon gamma can have a suppressive effect. Cytokines
      may also have to be administered at the same site or even to the same cell as the
      antigen for optimal effect. Conjugation or molecular chimerization of antigens
      and cytokines can achieve this effect efficiently. Formulation of cytokine with
      antigen may overcome any detrimental effect that the antigen may have. Should the
      antigen have any suppressive epitopes or have a direct effect on essential
      intracellular mechanisms, cytokines may be used to overcome these effects. In
      some cases, Th1 or Th2 cytokines have been used to enhance a protective Th1 or
      Th2 response. However, the paradigm does not always hold, and Th1 cytokines can
      enhance Th2 responses, or have no overall effect on phenotype. Further, in some
      host species, there is evidence that there may be no Th1/Th2 dichotomy. The most
      important aspect of using cytokines as adjuvants is in ensuring that there is a
      balanced response.

PMID- 9656449
TI  - Pathogen interactions with cytokines and host defence: an overview.
AB  - This review summarises some of the immune evasion tactics adopted by pathogens.
      They include the antagonism of immune function through the use of homologues of
      cytokine receptors, expression of viral proteins which interact with cytokine
      signal transduction and expression of cytokine mimics and host proteins that
      influence the Type I or II cytokine responses. Some of the viral defense
      molecules that interfere with the functions of cytokines include the EBV protein
      BCRF1 (viral IL-10) which blocks synthesis of cytokines such as IFN-gamma, viral
      IL-17 and IL-8 receptor encoded by the herpesvirus saimiri genome and chemokine
      receptor homologues of Epstein-Barr virus, herpesvirus saimiri and
      cytomegalovirus. These immunomodulatory tactics function to protect the host from
      the lethal inflammatory effects as well as inhibit the local inflammatory
      response elicited to kill the foreign pathogen. Other strategies include the
      alterations in cytokine expression such as demonstrated with the hepatitis B
      virus (HBV) core protein and terminal protein which can inhibit interferon-beta
      gene expression, the interactions of the hepatitis C virus core protein to
      lymphotoxin-beta receptor and the effects of the interferon signal transduction
      pathway by adenovirus EIA oncogene and HBV by reducing levels or activity of the
      cytosolic latent transcriptional factors (STATS). Immune evasive strategies of
      helminth parasites related to cytokine activities will also be briefly discussed.

PMID- 9656450
TI  - Poxvirus interference with the host cytokine response.
AB  - Poxviruses have evolved successfully to survive and replicate in a variety of
      species in the presence of an active host immune and inflammatory response. They
      manage this, at least in part, by the acquisition and modification of host immune
      and inflammatory response modulating genes. A proportion of these virulence genes
      encode homologues of host cytokines and cytokine receptors. These include soluble
      interferon, IL-1 beta, and TNF-alpha receptor homologues, that block the host
      cytokines. Other virulence gene products interfere with interferon signalling
      within cells and prevent the cleavage of biologically active IL-1 beta from its
      precursor protein. The parapoxvirus orf virus encodes a homologue of ovine IL-10
      and a novel GM-CSF-binding protein. By studying poxvirus virulence proteins that
      interfere with host cytokine effector responses, important and novel aspects of
      the host immune and inflammatory response to infection have been revealed.

PMID- 9656451
TI  - Differential migration of Th1 and Th2 cells--implications for vaccine and
      infection studies.
AB  - Most lymphocytes migrate continuously between the blood and lymphatic system.
      This migration does not occur randomly and shows some bias for specific tissue
      compartments. In particular, CD4+ memory T cells have been shown to
      preferentially migrate to either peripheral or mucosal lymph nodes depending on
      their site of origin. The selective migration of lymphocytes into lymph nodes is
      facilitated by the differential expression of adhesion molecules on the
      lymphocyte surface interacting with their respective ligands on endothelial cells
      lining the capillary vessels. The acquisition of these 'mucosal' or 'peripheral'
      homing receptors was thought to be dictated by the particular tissue site in
      which lymphocyte were activated. A large amount of recent experimentation has
      shown that memory T cells generated against infectious agents can have different
      functional phenotypes as determined by their cytokine secretion patterns. Two of
      these distinct functional phenotypes. Th1 and Th2 cells, are differentially
      induced in peripheral and mucosal lymph nodes and recent data has suggested that
      the observed tissue-specific migration of memory T cells may be determined by
      this functional phenotype rather than the site of activation. Data in support of
      this new hypothesis are presented in this paper. In addition, as both the
      functional and surface phenotype of lymphocytes is dependent on local hormonal
      and cytokine environments, lymphocyte migration patterns may be manipulated by
      vaccination and infection.

PMID- 9656452
TI  - Antibody and cytokine responses in efferent lymph following vaccination with
      different adjuvants.
AB  - The cannulated efferent lymph node in sheep was used to examine the effect of
      different adjuvants on the antibody and cytokine responses following sub
      cutaneous vaccination with a recombinant Taenia ovis antigen (45 W). Vaccination
      with Quil A elicited relatively higher levels of IgM than did IFA or Al(OH)3. In
      general, 45 W specific IgG1 and IgG2 titres were higher and maintained for longer
      periods of time in lymph from sheep vaccinated with IFA and lower and shorter
      lived in animals which received the Al(OH)3 based vaccine. Interferon-gamma was
      present within one day in efferent lymph from all sheep which received the Quil A
      formulation and in only one of the three sheep that received the IFA formulation.
      GM-CSF was only detected in lymph from sheep vaccinated with the IFA formulation.
      IL-8 was present in lymph prior to vaccination and only animals which received
      the Quil A formulation had increased levels of IL-8 after vaccination. Neither of
      the inflammatory cytokines IL-1 beta and TNF alpha were detected in efferent
      lymph from any animals in this study. This paper highlights the potential of the
      lymphatic cannulation model for investigations of the in vivo action of
      adjuvants.

PMID- 9656453
TI  - Oxidised mannan antigen conjugates preferentially stimulate T1 type immune
      responses.
AB  - It is desirable to be able to produce either T1 or T2 responses and we have found
      that, in mice, mannose--coupled antigens stimulated T2 type responses antibodies
      and CTLs, whereas if oxidized, mannose--coupled antigens stimulated T1 responses
      little antibody and a potent CTL response. In addition, the cytokine profiles
      support the T1rT2 differentiation with these immunizations, in that oxidized
      mannan antigen gives IFNg, IL-2 and IL-12 production, whereas in the absence of
      oxidization, IL-4 and not the other cytokines is produced. A number of antigens
      have been examined--particularly Mucin 1 and the delivery method using mannose
      may be applicable to the other antigens.

PMID- 9656454
TI  - Potential use of cytokine therapy in poultry.
AB  - Newly hatched chickens are highly susceptible to infection during the first 2
      weeks of life. The utilisation of cytokines as therapeutic agents in livestock
      animals, in particular poultry, has become more feasible with the recent cloning
      of cytokine genes and the progression of new technologies such as live vectors.
      We have constructed a live recombinant fowlpox virus (FPV) that expresses chicken
      myelomonocytic growth factor (fp/cMGF). Administration of fp/cMGF to chicks
      resulted in a marked and sustained increase in the number of circulating blood
      monocytes as well as an increase in their state of activation, as measured by
      enhanced phagocytic activity and elevated production of nitric oxide. We have
      recently cloned the gene for chicken interferon-gamma (ChIFN-gamma). Recombinant
      ChIFN-gamma was capable of protecting chick fibroblasts from undergoing virus
      mediated lysis and induced nitrite secretion from chicken macrophages in vitro.
      Preliminary vaccination trials have indicated that co-administration of ChIFN
      gamma with antigen (sheep red blood cells) resulted in enhanced secondary (IgG)
      antibody responses and allowed a 10-fold lower dose of antigen to be used.
      Furthermore, administration of ChIFN-gamma resulted in enhanced weight gain in
      chicks and improved their resistance to disease challenge. The ability of
      cytokines to combat infection and enhance vaccine efficacy makes them excellent
      candidates as a therapeutic agents and adjuvants.

PMID- 9656455
TI  - Rapid assessment of antigen induced cytokine expression in memory T cells by flow
      cytometry.
AB  - Methods for analysis of T cell responses to specific antigen have traditionally
      relied on measurements of proliferation or cytokine expression in bulk cultures
      of PBMC in long term incubations with putative antigen. These techniques suffer
      from the drawback that they do not enable analysis of single cell responses in
      the context of unselected cellular backgrounds. It is increasingly important to
      not only identify cells on the basis of expression of unique surface antigens but
      also to determine functional and molecular parameters of individual cells in
      response to a variety of stimuli. We have recently developed methodologies to
      rapidly assess T-cell subset responses to polyclonal activators and specific
      antigen in whole blood. These procedures determine the percentages of activated
      cells and the identification of leucocyte subsets capable of expressing various
      cytokines and cell surface antigens. Multiparameter analysis of CD69+ /cytokine +
      expression in T cells in response to specific antigen (e.g. CMV, mumps)
      demonstrated a range of frequencies from 0.05% to 5.0% within 6 h. Frequencies of
      responding T cells were consistent but varied depending upon the antigen. Antigen
      specific T cell responses were host specific and both positively and negatively
      regulated by antibodies to co-receptors involved in APC-T cell interactions.
      These technologies will be discussed in terms of application to problems of
      measuring immune function parameters in disease. The modified technique described
      in this report is compatible with simple and rapid analysis of clinical samples
      and provides a means to directly examine the effects of in vivo drug
      concentrations on T cell immunity. Studies are in progress to examine the
      sensitivity of this cellular assay to drugs and other therapeutic modalities in
      clinical samples.

PMID- 9656456
TI  - Increase in CD5+ B cells and depression of immune responses in sheep infected
      with Trypanosoma evansi.
AB  - The effects of Trypanosoma evansi on the cellular and humoral immune responses of
      sheep to Pasteurella haemolytica vaccine were studied. Peripheral blood
      lymphocytes (PBLs) from the sheep were analysed using single and double-colour
      indirect immunofluorescence staining and flow cytometry to monitor changes in
      circulating B and T cell subsets. Serum antibody responses were assayed using the
      enzyme-linked immunosorbent assay technique (ELISA), in addition to measuring
      local skin reactions at the site of vaccine administration. Results showed
      significant increases in circulating B cells in all sheep after the primary (p <
      0.01) and secondary (p < 0.001) vaccinations although the increases were much
      more dramatic in the T. evansi-infected sheep. In addition, infection induced
      significant increases (p < 0.004) both in proportions and numbers of CD5+ B cells
      with more than 70% of circulating B cells expressing the CD5 antigen and showed
      significant differences (p < 0.01) from those of control sheep in which
      vaccination alone failed to induce similar increases. Also, infection resulted in
      significant decreases in CD5+ (p < 0.003), CD4+ (p < 0.03) and CD8+ (p < 0.03) T
      cell subsets in contrast to their increases in all control animals after
      vaccination. Moreover, there were significant suppression of both local skin
      reaction (p < 0.005) and serum Ig and IgG1 (p < 0.001) antibody responses to the
      vaccine antigen.

PMID- 9656457
TI  - Production and characterisation of polyclonal antisera against feline IgE.
AB  - Cats, naturally or experimentally infected with Toxocara cati were immunised with
      dinitrophenylated ascaris antigen (DNP-Asc). All cats developed immediate skin
      reactivity to DNP coupled to bovine serum albumin (DNP-BSA) and the sera of the
      nine cats had a heat labile homocytotropic antibody detectable by homologous
      Prausnitz-Kustner (PK) tests. Reagin-rich fractions were prepared from these sera
      and used for the preparation of polyclonal antisera in rabbits. Resultant
      antisera were passed through a immunoabsorbent column of Sepharose 4B coupled to
      heated normal cat serum. An immunoabsorbent column prepared with the resultant
      antisera removed the PK reactivity from the cat sera, and the activity was
      recovered following acid elution. The antiserum failed to detect any recognised
      immunoglobulin in cat sera, but precipitated with a heat labile protein with
      gamma-1 electrophoretic mobility in the sera of parasited cats. These findings
      support the contention that the antisera are specific for feline IgE.

PMID- 9656458
TI  - Feline immunoglobulin E: induction of antigen-specific antibody in normal cats
      and levels in spontaneously allergic cats.
AB  - Sera from 10 cats with symptoms consistent with atopy, from 15 normal household
      cats and from 11 laboratory maintained cats were assessed for allergen-specific
      IgE and IgG to Dermatophagoides farinae (DF) by enzyme-linked immunosorbent assay
      (ELISA). In addition, 10 normal cats were immunised with DF and intradermal skin
      tests (IDST) were performed weekly. Sera from the latter were also assessed for
      DF-specific IgE by ELISA and using Prausnitz-Kustner (PK) tests. Although DF
      specific IgE was detectable in all the atopic cats, there was no significant
      difference between the levels in this group and in the clinically normal
      household cats. However levels in both these groups were significantly higher
      than those in the laboratory maintained cats. Detectable DF-specific IgE was
      induced in all of the 10 cats, but the levels were not correlated with the
      development of positive IDSTs, nor with the level of IgE as assessed by PK tests.
      These findings are consistent with a possible heterogeneity of IgE antibody in
      cats.

PMID- 9656459
TI  - Adjuvant effects of fluoride on oral immunization of chickens.
AB  - The present study was conducted to examine the antibody responses of chickens
      after oral immunization and the influence of sodium fluoride (NaF) on their
      immunological states. Bovine serum albumin (BSA) was used as an antigen, and the
      response was measured by enzyme-linked immunosorbent assays of serum samples,
      bile samples, and lachrymal fluids. Oral immunization of chickens with antigen
      alone hardly induced antibody responses in sera, bile samples or lachrymal
      fluids. Moreover, compared to control chickens, these orally immunized chickens
      exhibited a lower serum IgG response to subsequent parenteral immunization,
      suggesting that oral immunization induced immunological tolerance in chickens. A
      mucosal adjuvant, NaF, could abrogate oral tolerance and elicit an increase in
      antibody responses. Chickens, which received oral administration of antigen and
      NaF simultaneously, showed a significant rise in serum IgG antibody. Although
      there were variations among individual chickens and the titers were low, IgA
      antibodies were detected in bile samples and lachrymal fluids.

PMID- 9656460
TI  - Early immunopathological events in experimental ovine paratuberculosis.
AB  - An experimental oral infection of neonatal (< 2 weeks old) lambs with a cervine
      isolate of Mycobacterium avium subspecies paratuberculosis (M.a.
      paratuberculosis), the causal agent of ruminant paratuberculosis (Johne's
      disease) was used to investigate bacteriological, histopathological and
      immunological changes during the early (up to 8 weeks) post-infection phase. In
      vitro culture for mycobacteria was positive in one faecal and three mesenteric
      lymph node (MLN) samples from the eight infected lambs. All mycobacterial
      isolates from MLN were identified as M.a. paratuberculosis by polymerase chain
      reaction (PCR). Small-to-medium sized focal granulomata were observed in jejunal
      (JPP) and ileal Peyer's patches (IPP) from four of the eight infected lambs.
      Compared with controls, JPP from all infected lambs had significantly (p < 0.05)
      higher proportions of CD8+ and CD2+ lymphocytes, and there were significantly (p
      < 0.05) fewer cells expressing B lymphocyte-associated markers in IPP and MLN.
      The T/B cell ratio was significantly (p < 0.05) increased in both JPP and MLN
      from infected lambs. The expression of a range of genes for cytokines was
      examined using specific reverse transcriptase PCR (RT-PCR) amplification of
      messenger RNA (mRNA) template isolated from MLN, JPP and IPP from both groups of
      animals. Densitometric analyses indicated that, in infected animals, MLN
      expressed significantly (p < 0.05) more mRNA for TNF-alpha: JPP had significantly
      increased (p < 0.05) mRNA for GM-CSF and significantly decreased (p < 0.05) mRNA
      for IL-4 and IFN-gamma. Infected lambs had significantly (p < 0.05) decreased
      titres of both circulating IgG and gut mycobacteria-associated IgG antibody.
      Infection was not associated with any consistent changes in lymphocyte reactivity
      to specific mycobacterial antigens, IFN-gamma release into supernatants from in
      vitro intestinal lymphocyte cultures or gut IgA antibody levels.

PMID- 9656461
TI  - Low density blood granulocytic cells induced during classical swine fever are
      targets for virus infection.
AB  - Classical swine fever virus infection of pigs causes a severe leukopenia and
      immunosuppression. In the present study, the kinetics of virus infection, and
      identification of target cells for the virus in peripheral blood were analysed.
      Virus infection was often not detectable before 5-7 days p.i. A minority of
      animals yielded detectable infected cells at 3 days p.i., but < 5% PBMC. It was
      not until 10 days p.i. that this figure increased-to 35-70% PBMC depending on the
      animal. Detailed analysis of Ficoll-Hypaque-purified PBMC identified the major
      population to be SWC3+SWC8+CD14+MHCII- granulocytic cells. Microscopic
      observations determined that these low density granulocytic cells in the PBMC
      from CSFV infected animals were indeed immature cells. Both the low density
      granulocytic cells and monocytes were major targets for CSFV infection in the
      peripheral blood. This is the first demonstration that low density granulocytic
      cells dominate the blood leukocyte population during CSF, and that such cells are
      targets for virus infection. The present work also demonstrates that the
      leukocyte population changes, such as B lymphocyte depletion and the relative
      dominance of myeloid cells in the blood during CSF, occur before virus infection
      of the affected cells. Thus, the pathological mechanism therein is not a direct
      consequence of virus infection.

PMID- 9656462
TI  - Does Mycobacterium paratuberculosis survive current pasteurization conditions?

PMID- 9656463
TI  - Evidence for a genetic variation in the mitochondrial genome affecting traits in
      White Leghorn chickens.
AB  - A mitochondrial Mspl RFLP which was coselected with Marek's disease (MD)
      resistance in White Leghorn chickens was mapped to the NADH subunit IV. The RFLP
      was due to a transition, resulting in the change of the low-usage threonine
      triplet ACT (Mspl- allele) to the high usage triplet ACC (Mspl+ allele). Trait
      association studies within an unselected strain revealed that the Mspl- allele
      whose frequency was reduced in MD resistant strains was associated with high body
      weight and high egg specific gravity (a measure of eggshell thickness). Analysis
      at three different time points indicated a significant interaction between the
      mitochondrial genotype and the growth hormone genotype in early but not in late
      adulthood. The analysis indicates that mitochondrial variants may contribute to
      phenotypic variation in chickens and that such contributions may be dependent on
      the genetic background.

PMID- 9656464
TI  - Tracking the evolution of the elusive Andean mountain cat (Oreailurus jacobita)
      from mitochondrial DNA.
AB  - Rarely observed in the wild, the existence of the Andean mountain cat (Oreailurus
      jacobita) has been established based on only 3 skulls and 14 museum skins. The
      Andean mountain cat's evolutionary relationship to other felids based on
      morphological characters is largely contradictory, with evidence aligning it with
      South American small spotted cats (ocelot lineage) or alternatively with
      pantherine lineage felids. Here we describe the phylogenetic distinctiveness and
      placement of the Andean mountain cat using DNA extracted from pieces of nine
      independent pelt specimens, including one confiscated from a trapper in 1995. A
      phylogenetic analysis of DNA sequences from three rapidly evolving mitochondrial
      genes (16S rRNA, NADH-5, and ATP-8) indicate that the Andean mountain cat is a
      distinct species belonging to the ocelot lineage. Our findings suggest that the
      Andean mountain cat diverged from a common ancestor with the ocelot (Leopardus
      paradalis) and margay (L. wiedii) and exhibits moderate levels of genetic
      variation.

PMID- 9656465
TI  - Heritability estimates of behaviors associated with hunting in dogs.
AB  - Heritabilities of traits related to game-bird hunting, measured in the natural
      ability test of the North American Versatile Hunting Dog Association (NAVHDA),
      were calculated using midparent offspring regressions for five breeds of
      continental hunting dogs. Heritabilities of use of nose, search, and waterwork
      were moderate (0.25-0.39). Heritability of pointing was high (> 0.40) in one
      breed but only moderate in the combined dataset. Desire, cooperation, and
      tracking were not significantly correlated between midparent average and
      offspring. One of the breeds, large munsterlander, was analyzed for improvement
      over the past 15 years. The NAVHDA testing system is used to select breeding
      stock in the large munsterlander and improvement in scores was significant.

PMID- 9656466
TI  - Distortion of allele frequency distributions provides a test for recent
      population bottlenecks.
AB  - We use population genetics theory and computer simulations to demonstrate that
      population bottlenecks cause a characteristic mode-shift distortion in the
      distribution of allele frequencies at selectively neutral loci. Bottlenecks cause
      alleles at low frequency (< 0.1) to become less abundant than alleles in one or
      more intermediate allele frequency class (e.g., 0.1-0.2). This distortion is
      transient and likely to be detectable for only a few dozen generations.
      Consequently only recent bottlenecks are likely to be detected by tests for
      distortions in distributions of allele frequencies. We illustrate and evaluate a
      qualitative graphical method for detecting a bottleneck-induced distortion of
      allele frequency distributions. The simple novel method requires no information
      on historical population sizes or levels of genetic variation; it requires only
      samples of 5 to 20 polymorphic loci and approximately 30 individuals. The
      graphical method often differentiates between empirical datasets from
      bottlenecked and nonbottlenecked natural populations. Computer simulations show
      that the graphical method is likely (P > .80) to detect an allele frequency
      distortion after a bottleneck of < or = 20 breeding individuals when 8 to 10
      polymorphic microsatellite loci are analyzed.

PMID- 9656467
TI  - Juvenile bare: a new hair loss mutation on chromosome 7 of the mouse.
AB  - We describe a new juvenile hair loss mutant in the mouse in which the hair
      follicle follows irregular pathways to the surface and generally becomes
      dystrophic when the mouse is about 23 days of age. Skin from mutant mice older
      than 1 month of age is histologically normal, although adult mutant mice show a
      slightly more sparse coat than normal. Grafts of mutant littermates skin to SCID
      hosts indicate that the condition is probably a systemic response rather than one
      of the follicle per se. The hair loss is caused by a recessive mutation, which we
      have named juvenile bare (jb), located on proximal chromosome 7.

PMID- 9656468
TI  - Shorn (shn): a new mutation causing hypotrichosis in the Norway rat.
AB  - We report the identification of an autosomal recessive mutation in the Norway rat
      that causes an almost complete absence of normal hair. The mutation, named shorn
      (gene symbol shn), is distinct from fuzzy, hairless, and Rowett nude, and is not
      closely linked with any of these markers or with albino.

PMID- 9656469
TI  - Developmental stability in different genetic stocks of white rock chickens.
AB  - Asymmetries were determined for several bilateral traits in females from a line
      of chickens selected for 39 generations for low 56 day body weight (LWS) and in a
      subline of LWS where selection had been relaxed for four generations (LWR).
      Because of reduced food intake under ad libitum feeding, some LWS females do not
      commence egg production, a condition that can be overcome by relaxing selection
      for a generation or two. Bilateral traits, measured at 240 days of age in LWS non
      layers, LWS layers, and LWR layers, were shank length and diameter, distance
      between the auditory canal and the posterior junction of the upper and lower
      mandible, and weight and length of the first primary wing feather. Other traits
      measured were body weights at 56, 168, and 240 days of age and age at first egg.
      Fluctuating asymmetry, a good overall measure of developmental stability, was
      lower in the relaxed than selected line. Means of relative asymmetries were also
      lower for LWR females than LWS layers and nonlayers which were similar.

PMID- 9656470
TI  - Chromosome number of Severtzov's sheep (Ovis ammon severtzovi): G-banded
      karyotype comparisons within ovis.
AB  - Severtzov's sheep (Ovis ammon severtzovi; Nasonov 1914) has a 2n = 56 diploid
      chromosome number and a karyotype consisting of two pairs of biarmed and 25 pairs
      of acrocentric autosomes, a large acrocentric X, and a minute biarmed Y. The G
      banding patterns of the largest pair of biarmed chromosomes were identical to
      those of the largest biarmed chromosomes in all wild and domestic sheep of the
      genus Ovis. The banding patterns of the second pair of biarmed chromosomes were
      identical to the third pair of biarmed chromosomes in all sheep of the genus Ovis
      with 2n = 54 and to the third largest pair of chromosomes in the 2n = 52
      karyotype of the Siberian snow sheep (O. nivicola). The G-banded karyotype of
      Severtzov's sheep is consistent with all subspecies of argali (O. ammon spp.)
      that have been karyotyped. Numerical ascription of acrocentric chromosome
      equivalents based upon the fundamental karyotype of Ovis that gave rise to the
      biarmed chromosomes of severtzovi are 1 and 3, and 5 and 11 for the largest and
      second largest biarmed chromosomes, respectively. Based upon diploid chromosome
      number and G bands, Severtzov's sheep should be considered a subspecies of argali
      and not a urial.

PMID- 9656471
TI  - Locations of human genes for alpha 1A, alpha 1B, and alpha 1E calcium channels
      determined by radiation hybrid mapping.
AB  - To determine more detailed locations of human P/Q-type (alpha 1A), N-type (alpha
      1B), and R-type (alpha 1E) calcium channel genes, we have mapped CACNL1A4 (alpha
      1A), CACNL1A5 (alpha 1B), and CACNL1A6 (alpha 1E) loci using a radiation hybrid
      panel. Locations of these loci are as follows: WI-4669-5.1 cR3000-CACNL1A4-4.1
      cR3000-CHLC.GATA27C12 on chromosome 19; D9S158-2.0 cR3000-CACNL1A5-4.3 cR3000-WI
      14048 on chromosome 9; D1S215-4.4 cR3000-CACNL1A6-4.5 cR3000-D1S240 on chromosome
      1.

PMID- 9656472
TI  - Estimation of the proportion of triploids in populations with diploid and
      triploid individuals.
AB  - Populations with diploid and triploid individuals co-occur in various plant and
      animal species, but detecting their relative frequencies is problematic.
      Microsatellite markers can be used to detect triploids that have three distinct
      alleles at a given locus, but cannot identify triploids that are partially or
      fully homozygous (i.e., possessing two or three copies of the same allele).
      Detection of partially homozygous triploids is sometimes possible with allozymes
      if no dosage compensation occurs. However, the inference of triploidy from uneven
      band intensities is not always reliable, making it difficult to estimate the
      actual proportion of triploids in a population. We present an iterative
      mathematical procedure for estimating the overall proportion of triploids from
      allozyme and microsatellite data. This method also estimates corrected allele
      frequencies by accounting for potentially hidden cases of homozygosity occurring
      in triploid individuals with multiple copies of an allele.

PMID- 9656473
TI  - Intrinsic two-dimensional features as textons.
AB  - We suggest that intrinsic two-dimensional (i2D) features, computationally defined
      as the outputs of nonlinear operators that model the activity of end-stopped
      neurons, play a role in preattentive texture discrimination. We first show that
      for discriminable textures with identical power spectra the predictions of
      traditional models depend on the type of nonlinearity and fail for energy
      measures. We then argue that the concept of intrinsic dimensionality, and the
      existence of end-stopped neurons, can help us to understand the role of the
      nonlinearities. Furthermore, we show examples in which models without strong i2D
      selectivity fail to predict the correct ranking order of perceptual segregation.
      Our arguments regarding the importance of i2D features resemble the arguments of
      Julesz and co-workers regarding textons such as terminators and crossings.
      However, we provide a computational framework that identifies textons with the
      outputs of nonlinear operators that are selective to i2D features.

PMID- 9656474
TI  - Apparent contrast and spatial frequency of local texture elements.
AB  - We measured the apparent contrast and spatial frequency of a parafoveal Gabor
      signal located at the center of an array of Gabor signals as a function of both
      element density and the direction of contrast and spatial frequency of the
      surrounding elements. The target Gabor appeared lower in contrast and higher in
      spatial frequency when the elements were in close proximity, regardless of the
      direction of contrast and spatial frequency of the surrounding elements. Overall,
      the evidence suggests that the appearance of a parafoveal target is strongly
      affected by its visual context. These findings provide additional support for the
      existence of spatial interactions among neurons implicated in textural
      processing.

PMID- 9656475
TI  - Functional division of the retina and binocular correspondence.
AB  - Spatial vision relies on a spatial coding of object directions sensed by the
      retinal photoreceptors. An empirically measured constant error in this coding of
      perceived space is described classically as a barrel distortion involving long
      horizontal lines. A Cartesian retinal coordinate system is constructed to
      describe the transformation from object space to perceived space. This system
      establishes a subjective horizontal and vertical (isoelevation and isoazimuth)
      grid for each eye. The retinal entities that mediate subjective sense of constant
      elevation (horizontal) and constant azimuth (vertical) constitute the functional
      division of the retina, and they are described by a model with a single parameter
      zp, which determines the curvatures of a set of hyperbolic isopters. Empirical
      isoelevation positions were measured, which were described by this model. The
      best-fitting zp values appeared to be independent of viewing distance, similar
      for the two eyes of the same observer but differing significantly among
      observers. The functional-retinal-division model and horizontal retinal shear, as
      described by Helmholtz, were used to predict the spatial distributions of
      binocular corresponding points. The disparity field on a frontoparallel plane at
      a finite viewing distance showed marked asymmetry between the upper and the lower
      visual fields. The hyperbolic isoelevation and isoazimuth curves dramatically
      exaggerated this asymmetry. This theoretical disparity field provides a guideline
      for experiments that attempt to show the effect of binocular disparity in the
      periphery.

PMID- 9656476
TI  - Color-luminance interaction: data produced by oblique cross masking.
AB  - Threshold-elevation (TE-) versus-mask-spatial-frequency (SF) curves and TE-versus
      mask-contrast curves, produced by the oblique-masking technique, were reported
      for uncrossed stimuli (color-test-on-color-mask and luminance-test-on-luminance
      mask) [Invest. Ophthalmol. Visual Sci. Suppl. 34, 751 (1993) and Vision. Res. 23,
      873 (1983)]. The technique minimizes the artifacts that are due to spatial phase
      effects, spatial beats, spatial probability summation, and local cues. My goal
      was to measure these curves for crossed stimuli (color-test-on-luminance-mask and
      luminance-test-on-color-mask) by this oblique-masking technique and to compare
      the curves with those reported in previous studies. For this purpose threshold
      contrasts were measured by a yes-no procedure with randomized double staircases.
      Test targets were vertical spatially localized (D6) patterns, and masks were
      oblique sinusoidal patterns; both the test and the mask were presented
      simultaneously, for 2 s (Gaussian window), on a color monitor interfaced with an
      ATVista system and a Powell achromatizing lens. The test SF's were 0.125, 0.5, 2,
      4, and 8 cycles per degree (cpd); mask SF's were 0.031-16 cpd; and mask contrasts
      were 6.25%-50%. Furthermore, the Red-Green channel was defined by the minimum
      flicker and the hue cancellation techniques. Results show mostly masking effect
      (TE > 1) at contrasts above threshold; sometimes, separability (TE = 1) and above
      threshold facilitation (TE < 1) effects were also observed, depending on the test
      SF, the mask SF, the mask contrast, and the subject. In general, the magnitudes
      of TE's are smaller and the TE-versus-mask-SF curves are slightly narrower for
      the oblique-cross-masking conditions than those for the respective oblique
      uncross masking. In addition, the TE-versus-mask-contrast curves for the crossed
      conditions are mostly shallower than those for the respective uncrossed
      conditions. Furthermore, mostly the color-luminance asymmetry (color masks
      luminance more than luminance masks color) is found, in mild form, for SF's > or
      = 0.5 cpd. For the lower SF of 0.125 cpd, there is either a lack of asymmetry or
      a very mild asymmetry of the opposite kind (luminance masks color slightly more
      than color masks luminance) seems to prevail. In general, the oblique-masking
      data shows mild asymmetry and reduced facilitation; both are consistent with
      reduced local cues, similar to those shown by randomized phase data, thus making
      the data suitable for SF analysis; moreover, at high contrast, the masking data
      are consistent with those reported in previous studies.

PMID- 9656477
TI  - Identification of illuminant and object colors: heuristic-based algorithms.
AB  - In everyday scenes, from perceived colors of objects and terrains, observers can
      simultaneously identify objects across illuminants and identify the nature of the
      light, e.g., as sunlight or cloudy. As a formal problem, identifying objects and
      illuminants from the color information provided by sensor responses is
      underdetermined. It is shown how the problem can be simplified considerably by
      the empirical result that chromaticities of sets of objects under one illuminant
      are approximately affine transformations of the chromaticities under spectrally
      different illuminants. Algorithms that use the affine nature of the correlation
      as a heuristic can identify objects of identical spectral reflectance across
      scenes lit simultaneously or successively by different illuminants. The relative
      chromaticities of the illuminants are estimated as part of the computation.
      Because information about objects and illuminants is useful in many different
      tasks, it would be more advantageous for the visual system to use such algorithms
      to extract both sorts of information from retinal signals than to discount either
      automatically at an early neural stage.

PMID- 9656478
TI  - Range estimation by optical differentiation.
AB  - We describe a novel formulation of the range recovery problem based on
      computation of the differential variation in image intensities with respect to
      changes in camera position. This method uses a single stationary camera and a
      pair of calibrated optical masks to measure this differential quantity directly.
      We also describe a variant based on changes in aperture size. The subsequent
      computation of the range image involves simple arithmetic operations and is
      suitable for real-time implementation. We present the theory of this technique
      and show results from a prototype camera that we have constructed.

PMID- 9656479
TI  - Measurement of smoothed Wigner phase-space distributions for small-angle
      scattering in a turbid medium.
AB  - We study Wigner phase-space distributions W (x, p) in position (x) and momentum
      (p) for light undergoing multiple small-angle scattering in a turbid medium.
      Smoothed Wigner phase-space distributions are measured by using a heterodyne
      technique that achieves position and momentum resolution determined by the width
      and the diffraction angle of the local oscillator beam. The sample consists of
      5.7-micron-radius polystyrene spheres suspended in a water-glycerol mixture. The
      momentum distribution of the transmitted light is found to contain a ballistic
      peak, a narrow diffractive pedestal, and a broad background. The narrow
      diffractive pedestal is found to decay more slowly than the ballistic peak as the
      concentration of scatterers is increased. The data are in excellent agreement
      with a simple theoretical model that explains the behavior of the narrow pedestal
      by including multiple diffractive scattering and treating large-angle scattering
      as a loss.

PMID- 9656480
TI  - The mosaic nature of the eukaryotic nucleus.
AB  - The phylogenies for each of the protein-coding genes from the Methanococcus
      jannaschii genome were surveyed to determine the history of the major groups of
      life. For each gene, homologous sequences from other archaea, eucarya, and Gram
      positive and Gram-negative bacteria were collected and aligned, and a phylogeny
      was reconstructed with a maximum-likelihood algorithm. The majority of
      significant phylogenies favor the eucarya and the archaca as sister groups. A
      smaller, but still substantial, portion of these significant phylogenies favor an
      eucarya/Gram-negative clade. These results indicate that support for the early
      history of life is not unequivocal. A chimeric origin of eukaryotes or an
      ancient, massive horizontal transfer of genes from Gram-negative bacteria to
      eucarya can explain many of the observed phylogenies.

PMID- 9656481
TI  - Repeated evolution of an acetate-crossfeeding polymorphism in long-term
      populations of Escherichia coli.
AB  - Six out of 12 independent replicate populations of Escherichia coli maintained in
      long-term glucose-limited continuous culture for up to approximately 1,750
      generations evolve polymorphisms maintained by acetate crossfeeding. In all
      cases, the acetate-crossfeeding phenotype is associated with semiconstitutive
      overexpression of acetyl CoA synthetase, which allows for the enhanced uptake of
      low levels of exogenous acetate. Mutations in the 5' regulatory region of the
      acetyl CoA synthetase locus are responsible for all the acetate crossfeeding
      phenotypes found. These changes were either transposable-element insertions or a
      single T-->A nucleotide substitution at position -93 relative to the acs gene
      translation start site.

PMID- 9656482
TI  - Phylogenetic relationships and developmental expression of three sea urchin Wnt
      genes.
AB  - The Wnt genes comprise a family of secreted glycoproteins involved in cell-cell
      signaling and pattern formation during the development of a variety of organisms.
      We have begun to examine Wnt gene expression in sea urchins that exhibit
      alternative modes of larval development but produce similar adults. Here we
      describe the isolation of five Wnt sequences from indirect- and direct-developing
      sea urchin species using a PCR-based strategy and library screening. Phylogenetic
      and distance analyses indicate that the five sequences represent sea urchin Wnt
      1, -4, and -5 orthologs. Wnt-5 sequences were isolated from three sea urchin
      species and show a significantly faster rate of evolution than do their
      counterparts in jawed vertebrates. The genomic structure of the Wnt-5 locus was
      also examined, and its organization is similar to that of Wnt genes from insects
      and vertebrates. The temporal expression of all three sea urchin Wnt orthologs
      during sea urchin development was examined by RNA gel blots or RNase protection
      assays. Transcripts from all three sea urchin Wnts are detected at various
      developmental stages of both indirect- and direct-developing species. These data
      support the view that sea urchin Wnt genes exhibit many conserved aspects and at
      least three orthologs are developmentally regulated in both indirect- and direct
      developing sea urchin embryos.

PMID- 9656483
TI  - Long-range base pairing in Drosophila and human mRNA sequences.
AB  - The potential for long-range base pairing between the 5' and 3' ends of mRNA
      molecules was examined for 134 Drosophila and 204 human sequences collected from
      the GenBank database. Each sequence was divided into two parts, a 5' sequence
      taken from the start of the protein-encoding region and a 3' sequence taken from
      the end of the transcript. The strongest RNA pairing stem between each pair of 5'
      and 3' sequences was identified and scored using an alignment program modified to
      incorporate RNA base pairing. The observed pairing scores were then compared with
      a random distribution of scores generated by aligning each 5' sequence to random
      permutations of its corresponding 3' sequence. For both the Drosophila and the
      human mRNAs, the observed pairing scores were significantly biased toward the
      upper tail of the random distributions, with 61% of the Drosophila sequences and
      64% of the human sequences falling within the upper half of the random
      distributions. This suggests that a pattern of long-range base pairing may be a
      common feature of eukaryotic mRNAs. We have also analyzed a subset of Drosophila
      and human mRNAs which show the greatest potential for long-range pairing. The
      human pairings appear to be stronger and localized to more specific regions near
      the ends of the mRNA sequence than those of Drosophila.

PMID- 9656484
TI  - The evolutionary analysis of the Tnt1 retrotransposon in Nicotiana species
      reveals the high variability of its regulatory sequences.
AB  - We studied the evolution of the tobacco Tnt1 retrotransposon by analyzing Tnt1
      partial sequences containing both coding domains and U3 regulatory sequences
      obtained from a number of Nicotiana species. We detected three different
      subfamilies of Tnt1 elements, Tnt1A, Tnt1B, and Tnt1C, that differ completely in
      their U3 regions but share conserved flanking coding and LTR regions. U3
      divergence between the three subfamilies is found in the region that contains the
      regulatory sequences that control the expression of the well-characterized Tnt1
      94 element. This suggests that expression of the three Tnt1 subfamilies might be
      differently regulated. The three Tnt1 subfamilies were present in the Nicotiana
      genome at the time of species divergence, but have evolved independently since
      then in the different genomes. Each Tnt1 subfamily seems to have conserved its
      ability to transpose in a limited and different number of Nicotiana species. Our
      results illustrate the high variability of Tnt1 regulatory sequences. We propose
      that this high sequence variability could allow these elements to evolve
      regulatory mechanisms in order to optimize their coexistence with their host
      genome.

PMID- 9656485
TI  - Structural, genomic, and phylogenetic analysis of Lian, a novel family of non-LTR
      retrotransposons in the yellow fever mosquito, Aedes aegypti.
AB  - A retrotransposon named Lian-Aa1 was discovered in an intron of an AaHR3-1 gene
      of the yellow fever mosquito, Aedes aegypti. This retrotransposon contained a
      long open reading frame with 1,219 amino acids that included endonuclease,
      reverse transcriptase, and RNase H domains. It was shown that in the Rock strain
      of Ae. aegypti, there were up to 1,380 copies of Lian elements, equivalent to
      0.8% of the entire genome. Five additional copies of Lian elements were isolated,
      mapped by restriction digestion, and partially sequenced. The 5' and 3' ends of
      the Lian family were determined by comparing the terminal sequences of the six
      copies and were subsequently confirmed by the identification of putative target
      duplications flanking Lian-Aa1 and Lian-Aa2. The Lian family is likely a novel
      family of non-long-terminal-repeat (non-LTR) retrotransposons that terminate in a
      repeat of (CTGA-TAC)2. On average, the six copies of Lian elements showed only
      0.6% sequence divergence at the nucleotide level in both a 735-bp region at the
      5' end and a 1,124-bp coding region. Genomic Southern blots also revealed a very
      high degree of similarity among hundreds of Lian elements, suggesting very recent
      activity of Lian. Furthermore, all six analyzed Lian elements were closely
      associated with one or more different families of repetitive elements. It is
      possible that these associations could reflect the complex relationship between
      Lian elements and the rest of the Ae. aegypti genome. Phylogenetic analyses based
      on the reverse transcriptase, domains of 36 non-LTR retrotransposons including
      Lian-Aa1 identified five major subgroups that were supported by bootstrap
      replications. In contrast to the majority of non-LTR retrotransposons, Lian-Aa1
      has an RNase H domain that is similar to a few other non-LTR retrotransposons and
      some retroviruses, which is consistent with the previously proposed independent
      assortment of different domains during the evolution of retroelements.

PMID- 9656486
TI  - Phylogenetic tests of the hypothesis of block duplication of homologous genes on
      human chromosomes 6, 9, and 1.
AB  - There are 10 gene families that have members on both human chromosome 6 (6p21.3,
      the location of the human major histocompatibility complex [MHC]) and human
      chromosome 9 (mostly 9q33-34). Six of these families also have members on mouse
      chromosome 17 (the mouse MHC chromosome) and mouse chromosome 2. In addition,
      four of these families have members on human chromosome 1 (1q21-25 and 1p13), and
      two of these have members on mouse chromosome 1. One hypothesis to explain these
      patterns is that members of the 10 gene families of human chromosomes 6 and 9
      were duplicated simultaneously as a result of polyploidization or duplication of
      a chromosome segment ("block duplication"). A subsequent block duplication has
      been proposed to account for the presence of representatives of four of these
      families on human chromosome 1. Phylogenetic analyses of the 9 gene families for
      which data were available decisively rejected the hypothesis of block duplication
      as an overall explanation of these patterns. Three to five of the genes on human
      chromosomes 6 and 9 probably duplicated simultaneously early in vertebrate
      history, prior to the divergence of jawed and jawless vertebrates, and shortly
      after that, all four of the genes on chromosomes 1 and 9 probably duplicated as a
      block. However, the other genes duplicated at different times scattered over at
      least 1.6 billion years. Since the occurrence of these clusters of related genes
      cannot be explained by block duplication, one alternative explanation is that
      they cluster together because of shared functional characteristics relating to
      expression patterns.

PMID- 9656487
TI  - Inferring pattern and process: maximum-likelihood implementation of a
      nonhomogeneous model of DNA sequence evolution for phylogenetic analysis.
AB  - A nonhomogeneous, nonstationary stochastic model of DNA sequence evolution
      allowing varying equilibrium G + C contents among lineages is devised in order to
      deal with sequences of unequal base compositions. A maximum-likelihood
      implementation of this model for phylogenetic analyses allows handling of a
      reasonable number of sequences. The relevance of the model and the accuracy of
      parameter estimates are theoretically and empirically assessed, using real or
      simulated data sets. Overall, a significant amount of information about past
      evolutionary modes can be extracted from DNA sequences, suggesting that process
      (rates of distinct kinds of nucleotide substitutions) and pattern (the
      evolutionary tree) can be simultaneously inferred. G + C contents at ancestral
      nodes are quite accurately estimated. The new method appears to be useful for
      phylogenetic reconstruction when base composition varies among compared
      sequences. It may also be suitable for molecular evolution studies.

PMID- 9656488
TI  - Nuclear gene trees and the phylogenetic relationships of the mangabeys (Primates:
      Papionini).
AB  - Phylogenetic relationships of mangabeys within the Old World monkey tribe
      Papionini are inferred from analyses of nuclear DNA sequences from five unlinked
      loci. The following conclusions are strongly supported, based on congruence among
      trees derived for the five separate gene regions: (1) mangabeys are polyphyletic
      within the Papionini; (2) Cercocebus is the sister taxon to the genus Mandrillus;
      and (3) Lophocebus belongs to a clade with Papio and Theropithecus, with Papio as
      its most likely sister taxon. Morphologically based phylogenies positing mangabey
      monophyly were evaluated by mapping the sequences for each locus on these trees.
      The data seem to fit these trees poorly in both maximum-parsimony and likelihood
      analyses. Incongruence among nuclear gene trees occurred in the
      interrelationships among Lophocebus, Papio, and Theropithecus. Several factors
      that may account for this incongruence are discussed, including sampling error,
      random lineage sorting, and introgression.

PMID- 9656489
TI  - Sex-related genes, directional sexual selection, and speciation.
AB  - Reproductive isolation and speciation can result from the establishment of either
      premating or postmating barriers that restrict gene flow between populations.
      Recent studies of speciation have been dominated by a molecular approach to
      dissect the genetic basis of hybrid male sterility, a specific form of postmating
      reproductive isolation. However, relatively little attention has been paid to the
      evolution of genes involved in premating isolation and genes generally involved
      in other sex-related functions (e.g., mating behavior, fertilization,
      spermatogenesis, sex determination). We have assembled DNA sequences from 51
      nuclear genes and classified them based on their functional characteristics. The
      proportion of nonsynonymous to synonymous nucleotide substitutions were compared
      between Drosophila melanogaster, Drosophila simulans, and Drosophila
      pseudoobscura, as well as between Caenorhabditis elegans and Caenorhabditis
      briggsae. We found a high ratio of nonsynonymous to synonymous substitutions for
      sex-related genes (i.e., genes involved in mating behavior, fertilization,
      spermatogenesis, or sex determination). The results suggest that directional
      sexual selection has shaped the evolution of sex-related genes and that these
      changes have more likely occurred during the early stages of speciation. It is
      possible that directional selection becomes relaxed after reproductive isolation
      has been completed between more distantly related species (e.g., D. melanogaster
      and D. pseudoobscura). However, a saturation in the number of nucleotide
      substitutions since the time of species separation may mask any sign of
      directional selection between more distantly related species.

PMID- 9656490
TI  - Evolutionary distances for protein-coding sequences: modeling site-specific
      residue frequencies.
AB  - Estimation of evolutionary distances from coding sequences must take into account
      protein-level selection to avoid relative underestimation of longer evolutionary
      distances. Current modeling of selection via site-to-site rate heterogeneity
      generally neglects another aspect of selection, namely position-specific amino
      acid frequencies. These frequencies determine the maximum dissimilarity expected
      for highly diverged but functionally and structurally conserved sequences, and
      hence are crucial for estimating long distances. We introduce a codon-level model
      of coding sequence evolution in which position-specific amino acid frequencies
      are free parameters. In our implementation, these are estimated from an alignment
      using methods described previously. We use simulations to demonstrate the
      importance and feasibility of modeling such behavior; our model produces linear
      distance estimates over a wide range of distances, while several alternative
      models underestimate long distances relative to short distances. Site-to-site
      differences in rates, as well as synonymous/nonsynonymous and first/second/third
      codon-position differences, arise as a natural consequence of the site-to-site
      differences in amino acid frequencies.

PMID- 9656491
TI  - A degenerate group II intron in the intronless mitochondrial genome of
      Chlamydomonas reinhardtii: evolutionary implications.

PMID- 9656492
TI  - A SINE that acquired a role in signal transduction during evolution.

PMID- 9656493
TI  - The most ancient DNA recovered from an amber-preserved specimen may not be as
      ancient as it seems.

PMID- 9656494
TI  - The boiling point.

PMID- 9656495
TI  - Cheers for eloquent 'right man syndrome' editorial.

PMID- 9656496
TI  - Polypharmacy is not an example of scientific-based medicine, either.

PMID- 9656497
TI  - Another look at 'the evil eye'.

PMID- 9656498
TI  - Collaborators in care: the New England Center for Integrative Health blends
      naturopathy and conventional medicine.

PMID- 9656499
TI  - The psychosomatic network: foundations of mind-body medicine.
AB  - Research in the 1980s uncovered ubiquitous neuropeptide-receptor distribution in
      brain structures associated with emotional processing, and throughout many organ
      systems. This finding supported neuropeptides as biochemical substrates of
      emotion, and the neuropeptide-receptor network as a parasynaptic system crossing
      traditional brain-body boundaries. The medical relevance of these findings was
      affirmed by psychoneuroimmunology research: neuropeptides help to regulate
      immunocyte trafficking, there is bidirectional communication between nervous and
      immune system components, immunocytes produce neuropeptides, and nerve cells
      produce immune-associated cytokines. In the past decade, the concept of a unified
      psychosomatic network has been strengthened by animal and human research
      demonstrating relationships between behavior and neuropeptide-mediated regulation
      of immune functions. Research on emotional expression or disclosure in healthy
      human subjects as well as in cancer and HIV-positive patients has shown
      significant positive correlations with clinically relevant immune functions
      and/or positive health outcomes. Psychosocial interventions emphasizing emotional
      expression or active coping have evidenced survival benefits in breast cancer and
      melanoma. These findings suggest that emotional expression generates balance in
      the neuropeptide-receptor network and a functional healing system. Emotional
      expression is also a marker for psychospiritual vitalization, and further
      research should evaluate links between energy-based models of health and
      neuropeptide-receptor-based models under the rubric of an informational paradigm.

PMID- 9656500
TI  - The use of complementary medicine for healthy aging.
AB  - By the year 2020, twenty percent of the US population will be aged 65 years or
      older. The greatest growth in numbers will be among those aged 85 years or older.
      If the healthcare demands of this group match those of their parents, it will
      place an extraordinary burden on funding for medical services. By promoting
      healthy aging, complementary medicine practitioners can improve the cost
      effectiveness of healthcare delivery. A scientifically based complementary
      medicine program to promote healthy aging includes (1) diet and nutritional
      tailoring, (2) nutrient enhancement to meet specific individual needs, (3)
      exercise training, (4) stress management, (5) promotion of structural integrity,
      (6) environmental adjustment, (7) counseling on purposeful living, and (8)
      normalizing intercellular communication. The program described in this article
      incorporates these features and focuses on the following modifiable factors of
      unhealthy aging: altered mitochondrial function and oxidative stress, increased
      protein glycation, chronic inflammation, defects in methylation, reduced
      detoxification ability, and altered immunity.

PMID- 9656501
TI  - Psychological aspects of mind-body medicine: promises and pitfalls from research
      with cancer patients.
AB  - Research in psychosocial oncology has grown considerably. In this article,
      psychological interventions for cancer patients are reviewed. The following four
      areas are examined: (1) adjustment and quality of life, (2) symptom control, (3)
      immune function, and (4) disease progression. In each area, psychosocial
      dimensions of risk and resilience, the efficacy of current interventions, and the
      trajectory of future developments are considered.

PMID- 9656502
TI  - A multimethod research study on the use of complementary therapies among patients
      with inflammatory bowel disease.
AB  - CONTEXT: The purpose of this study was to gain a better understanding of the use
      of complementary therapies among patients with inflammatory bowel disease.
      OBJECTIVE: To examine factors influencing the use of complementary therapies, to
      explore patient-physician communication concerning those therapies, and to assess
      the effect of combining qualitative with quantitative research. DESIGN: In-depth
      qualitative interviews. PARTICIPANTS: Fourteen patients were selected from a
      quantitative study in which the use of complementary therapies among patients
      with inflammatory bowel disease was assessed. RESULTS: Patients reported using
      complementary therapies because of the serious side effects of medical treatment,
      because they felt conventional treatments did not help, and because complementary
      therapies were thought to be safe. Psychological and social factors for using
      complementary therapies must be considered and understood. Patients cited many
      reasons for not discussing the use of complementary therapies with their doctors.
      Adding qualitative data to quantitative research greatly increased the authors'
      understanding of factors that contribute to complementary therapy use.
      CONCLUSIONS: Multiple factors contribute to the decision to use complementary
      therapies among those with inflammatory bowel disease. Identifying these factors
      is important for educating physicians regarding their patients' use of
      complementary therapies and may contribute to improved patient-physician
      communication.

PMID- 9656503
TI  - A birth intervention: the therapeutic effects of Doula support versus Lamaze
      preparation on first-time mothers' working models of caregiving.
AB  - CONTEXT: A working model of caregiving has been defined as an internalized schema
      of caregiving that guides a mother's behavior with her infant. This schema is
      strongly influenced by the mother's first attachment relationship with her own
      mother, which frequently operates outside her conscious awareness. OBJECTIVE: To
      examine doula support at birth as an intervention that might correct distortions
      of a mother's unconscious schema of caregiving, promoting more secure caregiving
      following childbirth. DESIGN: The effects of doula support versus Lamaze birth
      preparation on the working models of caregiving of 35 first-time pregnant mothers
      were compared. INTERVENTIONS: An interview was used to assess the mothers'
      working models in the third trimester of pregnancy and again 4 months after the
      mothers gave birth. Mood state and self-esteem were measured at these times. A
      post hoc analysis was performed on the mothers' birth experiences, the quality of
      their postpartum support, and their evaluations of their infants' temperaments.
      RESULTS: The prebirth to postbirth rating analysis of the interviews revealed
      that the mothers in the doula group were significantly less rejecting and
      helpless in their working models of caregiving than were the mothers in the
      Lamaze group. The mothers in the doula group also showed greater security than
      did mothers in the Lamaze group, a difference that approached but did not reach
      significance. In addition, the women in the doula group were less emotionally
      distressed and had higher self-esteem than did the women in the Lamaze group, and
      the women in the doula group rated their infants as significantly less fussy than
      the mothers in the Lamaze group rated their infants. CONCLUSIONS: When viewed in
      the context of working models of caregiving, mothers who used a doula were
      significantly less rejecting and helpless, and approached significantly higher
      scores on the secure scale, than did mothers who used Lamaze birth preparation.
      Mothers rated as secure showed significantly less mood disturbance and higher
      prebirth and postbirth self-esteem than did mothers rated as insecure, providing
      construct validity for the caregiving interviews.

PMID- 9656505
TI  - Healing the practice of surgery.

PMID- 9656504
TI  - Marilyn Schlitz, PhD. On consciousness, causation, and evolution. Interview by
      Bonnie Horrigan.
AB  - Marilyn Schlitz is an anthropologist and director of research for the Institute
      of Noetic Sciences, where she develops and oversees research in three areas:
      emerging worldviews, inner mechanisms of the healing response, and extended human
      abilities. Before working for the Institute of Noetic Sciences, she was director
      of the Esalen Center for the Theory and Research Working Group on Direct Mental
      and Healing Interactions on Living Systems; a research associate in the
      Department of Sociology and Anthropology at Trinity University in Texas; an
      assistant research scientist at the Agricultural Research Station and Department
      of Rural Sociology at Texas A & M University; and a research associate and
      project director for the Mind Science Foundation. Dr Schlitz also has worked as a
      research consultant for the Stanford Research Institute and as a research fellow
      for the Foundation for Research on the Nature of Man at the Institute for
      Parapsychology. She has taught at many universities and colleges, including work
      as a lecturer in the Department of Psychology at Stanford, and as an instructor
      in the Department of Sociology and Anthropology at Trinity University. In 1994
      she received the Thomas Welton Stanford Psychical Research Fellowship. She
      received her doctoral degree in anthropology from the University of Texas in 1992
      and her master's degree in behavioral and social sciences in 1986, also from the
      University of Texas. Dr Schlitz has published numerous papers and book chapters
      on the topic of parapsychology. She speaks nationally and is involved with many
      research projects exploring the relationship between consciousness and the outer
      world.

PMID- 9656506
TI  - [Physical activity and diabetes mellitus].

PMID- 9656507
TI  - [Usual physical activity level, glycemic control, and cardiovascular risk factors
      profile. Spanish Diabetes Society Working Group for the study of Nutrition].
AB  - OBJECTIVES: To know the relation between the usual physical activity pattern and
      metabolic control and cardiovascular risk factors of people with diabetes
      mellitus. RESEARCH DESIGN AND METHODS: 144 type 1 (insulin dependent) diabetic
      subjects (M/F, 70/74) and 193 type 2 (non insulin dependent) diabetic patients
      8M/F, 81/112) fron DNCT study (Diabetes Nutrition and Complications Trial) were
      included in the study from May 1993 to December 1994. Physical activity index was
      assessed by means of the weekly caloric expenditure based upon previously
      published questionnaire. RESULTS: At least 60% of diabetic patients had a regular
      exercise more than 3 times per week. Unexpected, level of HbA1c, but not other
      parameters, was related to the level of physical activity, in that the higher the
      activity the higher HbA1c level in both type 1 and type 2 diabetic patients.
      CONCLUSIONS: In the DNCT study the higher physical activity level was associated
      a worsening in the HbA1c level. These un expected date there are take into
      account when recommending physical activity to people with diabetes mellitus with
      no good metabolic control.

PMID- 9656508
TI  - [Prevalence of latent toxoplasma infection in HIV infection patients].
AB  - BACKGROUND: To know the prevalence of Toxoplasma gondii latent infection in HIV-1
      infected patients and to compare it with the prevalence in a group of parenteral
      drug users, non-infected by HIV. METHODS: We study 255 HIV-1 patients revised in
      our hospital in the last 6 years. The control group were 116 drug addicts non
      infected by HIV followed in an educational program of deshabituation. We tested
      IgG anti-toxoplasma by enzymatic inmunoessay (MEIA). An IgG plasma value of
      6UI/ML or more was an indicative of toxoplasma previous infection. We used Chi
      Square and Yatchts correction tests for the statistical analysis, settling down a
      significance point of 95%. RESULTS: We founded 36.7% positive IgG anti-toxoplasma
      in the group on HIV-1 infected patients, non drugs addicts, against 30.9% in the
      group of HIV-1 drug addicts patients. (OR 0.77; 0.35 < OR < 1.66). The control
      group showed a Toxoplasma seroprevalence of 26.7%, without statistically
      significant against the drug addicts HIV group (OR = 1.55; 0.93 < OREGON < 2.59).
      CONCLUSIONS: The seroprevalence of Toxoplasma gondii latent infection in our
      study was similar to the european results. We didn't found a higher prevalence in
      HIV-1 patients than in patients non infected by HIV-1.

PMID- 9656509
TI  - [Visceral leishmaniasis in immunocompromised patients].
AB  - OBJECTIVE: Most patients who developed visceral leishmaniasis (VL) in our country
      are immunocompromised (IC) host, frequently HIV-infected patients. One objective
      was to know if there were differences about the clinical manifestations,
      diagnostic tests or prognosis in IC patients who were infected or not with HIV
      (HIV+ and HIV-, respectively). Also we wonder if some features were associated
      with death during the initial episodes of VL. METHOD: We studied 16 IC patients
      with VL, 9 were VIH+ and 7 were VIH-. Most frequently observed findings were
      fever (94%), splenomegaly (81%), hepatomegaly (69%), and constitutional syndrome
      (50%). HIV+ patients had symptoms during a lapse of time (70 +/- 78 days) larger
      than the VIH- cases had (17 +/- 12 days, p < 0.05). RESULTS: We performed a
      serology to Leishmania sp in 15 cases (94%) and were positive in 13 patients (77%
      in HIV+ and 100% in VIH patients). Seven patients (44%, 4 VIH- and 3 VIH+) died
      during the initial episode of VL. Nine patients (66%) who survived to it were
      followed-up during 68 +/- 49 months. Seven patients (4 VIH+ and 3 VIH-) showed
      several relapses (2.5 +/- 1.6 relapses/patient) through the follow-up. The
      patients who died during the initial episode had more frequently (p < 0.05)
      concentrations of albumin below 3 g/dl or of globulins below 4 g/dl, than the
      survivors had. The CD4+ lymphocyte counts in HIV+ patients were lower in patients
      who died during the initial episode of VL (19 +/- 15/mm) than in survivors (108
      +/- 67/mm3, p = 0.07).

PMID- 9656510
TI  - [Decisions regarding cholesterol-lowering therapy in the elderly: the experience
      in a lipid clinic and a review of the literature].
AB  - BACKGROUND: Therapy for hypercholesterolemia is long known one of the
      interventions with higher benefit on coronary heart disease secondary prevention
      and on primary prevention in middle-age high-risk people. Data about elderly
      persons are more scarce. The aim of this work is to study elderly patients sent
      to a Lipid Clinic, focusing on Serum Lp (a) levels and criteria to prescript
      cholesterol-lowering drugs. We have reviewed current knowledge to discuss and to
      clarify these criteria. METHOD: Observational study. Review of the medical charts
      from the patients sent to the Lipid Clinic. Elderly patients were compared with
      middle-aged persons attended to the same Clinic. RESULTS: From 348 total Lipid
      Clinic cohort 72 (20.7%) patients were more than 65 years old (31 male). A 3
      months or longer follow-up was available in 49/72 and 36/49 were taking
      cholesterol-lowering drugs. Among these 36, 21 had coronary disease; the other 15
      had, at least, another risk factor, besides dyslipidemia. Serum Lp (a) level were
      higher in older group (38.7 +/- 36.9 mg/dl, median 29, vs 26.3 +/- 24.2, median
      18 mg/dl, p < 0.01). Considering the accepted cardiovascular risk threshold (Lp
      (a) > 30 mg/dl), difference were found only in women. Coronary disease was
      present in 79 patients followed 3 months or longer and 24/79 were more than 65
      years old. Twenty-one of them were taking cholesterol-lowering drugs, vs 50 from
      the 55 younger (pNS). The reasons for no drug-therapy were similar in both
      groups. CONCLUSIONS: Coronary heart disease or cardiovascular risk factors
      association were the criteria used for starting cholesterol-lowering drug
      therapy. Published evidence supporting this therapeutic approach is reviewed.
      There were not found age related differences for cholesterol-lowering drugs
      prescriptions in patients suffering coronary disease. Serum Lp (a) level were
      higher in elderly sample because of the increase in older women; it could be
      linked to the postmenopausal hormonal state.

PMID- 9656511
TI  - [Vasculitis affecting the kidney: analysis of 18 patients].
AB  - OBJECTIVE: Eighteen patients who were judged to have systemic vasculitis (1990
      American College of Reumathology criteria) affecting the kidney, from January
      1988 to August 1996, were reviewed. METHOD: We analyzed characteristics of
      clinical, biochemical, histopathological features, the interval between the onset
      of the symptoms to a diagnosis of disease, treatment and overall outcome.
      RESULTS: The principal mode of presentation of the vasculitis is general, renal
      and pulmonary symptoms. The discovery of ANCA has improved the diagnostic
      procedure in patients with these diseases. Renal biopsy facilitates early
      diagnosis, prognosis and treatment. The renal lesion typically shows a segmental
      necrotizing glomerulonephritis and extracapillary proliferation forming crescent.
      CONCLUSIONS: The systemic vasculitis with renal involvement carries a poor
      prognosis and high mortality. A variety of treatment has been employed, but their
      precise role in the management of these vasculitis is still being elucidated.

PMID- 9656512
TI  - [Massive hepatic amyloidosis: a case of hepatic failure and haemorrhagic
      pancreatitis of fatal evolution].
AB  - Hepatic involvement is frequently in systemic amyloidosis but major clinical
      symptoms due to portal hypertension or liver failure are rare. To date all
      treatment modalities proven in these patients have failed. Thus, prognosis is
      dismal with progressive deterioration in liver function. We describe a patient
      with massive liver involvement by primary amyloidosis, manifested by severe
      intrahepatic cholestasis. Up to now 25 similar case have been reported in the
      English literature. In this subset of patients the most frequently recorded cause
      of death was renal failure accelerated by hyperbilirrubunemia. In our patient a
      downhill course was characterized by fatal renal hepatic failure after an
      hemoperitoneum, probably as a delayed complication of liver biopsy. Although not
      all authors agree, an added risk of bleeding after liver biopsy have been pointed
      out in hepatic amyloidosis. This kind of problem recommends the use of tissue
      other than liver, or a transjugular hepatic biopsy for diagnostic purposes. Also,
      of interest in the present cause is the autopsy findings of pancreatitis
      associated to pancreatic amyloidosis, a complication which have been described in
      previous reports.

PMID- 9656513
TI  - [Primary tracheobronchial amyloidosis. Report of a case].
AB  - We present a patient with primary tracheobronquial amiloidosis diffuse,
      presenting with asthma-like dysnea. The diagnosis was made through the
      broncoscopy and biopsy of infiltrated bronchial mucosa.

PMID- 9656514
TI  - [T-gamma lymphocytosis associated with two solid neoplasms in a patient with
      rheumatoid arthritis].
AB  - T gamma lymphocytosis is an infrequent entity, generally benign and distinct of
      the spectrum of the T cell chronic lymphoproliferative syndromes, that it not
      need or need short therapy, with a prolongated survival. T gamma lymphocytosis is
      expressive in the most of the occasions of a monoclonal lymphocytic proliferation
      and it is frequently associated to Rheumatoid Arthritis. We present the case of a
      patient with T gamma lymphocytosis, developed after several years of evolution of
      Rheumatoid Arthritis and that it was coincident with two solid neoplasms, an
      infiltrate carcinoma of the larynx and recurrent urothelial carcinoma, without
      previous chemotherapy. The death in this patients, is generally due a progressive
      lymphoproliferation and sepsis relationed with the neutropenia.

PMID- 9656515
TI  - [Acute pancreatitis complicating primary HIV-1 infection].
AB  - Primary HIV infection is usually paucisymptomatic, although 30-40% of patients
      show a mononucleosic syndrome of variable intensity and different manifestations.
      An increasing number of heterosexual HIV infection in Spain, and the fact of more
      severe manifestations in this subset of patients make necessary a deeper
      understanding of this complex clinical picture. We report a case of heterosexual
      primary HIV infection in a female patient without any known risk factor. This
      care evolued in an exceptionally severe form with meningitis and pancreatitis, to
      the best of our knowledge, this is the first reported care of pancreatitis
      complicating primary HIV-1 infection.

PMID- 9656516
TI  - [Coeliac disease in the adult].
AB  - Coeliac disease can by defined as a chronic disease characterized by a typical
      mucosal lesion of the small intestine and an impaired nutrient absorption which
      improves on withdrawal of gluten from the diet. The prevalence rate has increased
      over the last decades and just 1/3 of cases are diagnosed in childhood. There is
      a striking association with class II histocompatibility antigens, HLA-DR3 and HLA
      DQ2. Cellular immune response mediated by intraepithelial and lamina propria
      lymphocytes is the primary event in the small intestine damage. Up to 50% of
      adult coeliac patients don't present intestinal symptoms being more frequent
      subclinic forms. The immunological markers of coeliac disease are antigliadin,
      antireticulin and antiendomysial antibodies, being the last one the most
      specific. Mortality of coeliac patient is increased mainly for malignancies,
      being the most frequent the intestinal T lymphoma.

PMID- 9656517
TI  - [Value of rationalization in the clinical use of antibiotics].

PMID- 9656518
TI  - [Varicella pneumonia in healthy adults. Apropos of 7 cases].

PMID- 9656519
TI  - [Tuberculous pancreatitis in HIV infection].

PMID- 9656520
TI  - [Autoimmune thrombocytopenia from low molecular weight heparin].

PMID- 9656521
TI  - [Multiple cutaneous tumors as the first manifestation of lung adenocarcinoma].

PMID- 9656522
TI  - [Tuberculosis in HIV infected patients].

PMID- 9656523
TI  - [Severe hemolytic anemia secondary to cytomegalovirus infection in an
      immunocompetent adult].

PMID- 9656524
TI  - [Tuberculosis in the elderly].

PMID- 9656525
TI  - [Adverse reactions to insulin].

PMID- 9656526
TI  - [Gastric carcinoma in patients younger than 35 years of age].

PMID- 9656528
TI  - [Septic shock and multiple organ failure from Mycobacterium tuberculosis].

PMID- 9656527
TI  - [Norwegian scabies and sepsis from Escherichia coli in a HIV infected patient].

PMID- 9656529
TI  - [Norwegian scabies in patients with AIDS. Primary prophylaxis in a possible
      hospital outbreak].

PMID- 9656530
TI  - [Treatment of chronic viral hepatitis].

PMID- 9656531
TI  - [Antiretroviral treatment of HIV infection in children].

PMID- 9656532
TI  - [Diagnostic value of reactive C protein in suspected acute appendicitis in
      children].
AB  - OBJECTIVE: The aim of this study was to evaluate the accuracy of C-reactive
      protein (CRP) measurements in the diagnosis of suspected acute appendicitis (AA)
      during childhood. PATIENTS AND METHODS: A prospective study of 195 consecutive
      children, aged between 2 and 14 years and suspected of having AA, that attended a
      pediatric emergency room was carried out. We obtained a careful patient history,
      physical signs, blood test results, final diagnosis and the histological findings
      in the cases who underwent appendectomy (classified as normal appendix, simple
      appendicitis (SA) or gangrenous appendicitis (GA). RESULTS: The final diagnoses
      and their frequencies were: AA (94), non-specific abdominal pain (80), mesenteric
      lymphadenitis (6) and others (15). Appendectomies were performed in 103 cases
      with 94 cases being AA (91.3%) and of these 51 SA and 43 GA. The average values
      of CRP (mg/l) were: AA: 30, SA: 16, GA: 67, non-specific abdominal pain: 15, and
      mesenteric lymphadenitis: 44 (p < 0.01). The values of AG were statistically
      higher than those of SA (p = 0.0000). The ROC curve of these data determined the
      best cut-off levels for AA to be 30 (sensitivity: 0.43, specificity: 0.92,
      predictive value of a positive result: 0.87 and predictive value of a negative
      result: 0.58). CONCLUSIONS: 1) The value of CRP in AA is higher than in other
      abdominal pain etiologies. Nevertheless, this value should not be used to deny
      surgery since it is often normal in SA. 2) When a CRP value > 40 mg/L is found in
      a suspected AA, one should think about GA and therefore, initiate prophylactic
      antibiotics and perform surgery immediately.

PMID- 9656533
TI  - [Eyberg inventory of child behavior. Standardization of the Spanish version and
      its usefulness in ambulatory pediatrics].
AB  - OBJECTIVE: Taking into account the high prevalence of behavioral problems in the
      pediatric outpatient clinic, a need for a useful and easy to administer tool for
      the evaluation of this problem arises. The psychometric characteristics of the
      Spanish version of the Eyberg Behavioral Child Inventory (EBCI), [in Spanish
      Inventario de Eyberg para el Comportamiento de Nino (IECN)], a 36-item
      questionnaire were established. PATIENTS AND METHODS: The ECBI
      inventory/questionnaire was translated into Spanish. The basis of the ECBI is the
      evaluation of the child's behavior through the parents' answers to the
      questionnaire. Healthy children between 2 and 12 years of age were included and
      were taken from pediatric outpatient clinics from urban and suburban areas of
      Barcelona and from our hospital's own ambulatory clinic. RESULTS: The final
      sample included 518 subjects. The mean score on the intensity scale was 96.8 and
      on the problem scale 3.9. Internal consistency (Cronbach's alpha) was 0.73 and
      the test-retest had an r of 0.89 (p < 0.001) for the intensity scale and r = 0.93
      (p < 0.001) for the problem scale. Interrater reliability for the intensity scale
      was r = 0.58 (p < 0.001) and r = 0.32 (p < 0.001) for the problem scale.
      Concurrent validity between both scales was r = 0.343 (p < 0.001). CONCLUSIONS:
      The IECN is a useful and easy tool to apply in the pediatrician's office as a
      method for early detection of behavior problems.

PMID- 9656534
TI  - [Ophthalmoplegia-ataxia-areflexia in pediatrics. Three new patients and review of
      the literature].
AB  - OBJECTIVE: The objective of this study was to investigate if pediatric patients
      with benign brainstem encephalitis (Bickerstaff Syndrome) or with Miller-Fisher
      Syndrome are the extremes of the same nosological entity which, in adults, has
      been named ophalmoplegia-ataxia-areflexia syndrome. PATIENTS AND METHODS: The
      subjects included in the study were three patients of our institution and 24
      patients found in the revision of the English and Spanish pediatric literature
      who fulfilled the diagnostic criteria of ophtalmoplegia-ataxia-areflexia
      syndrome. The topographical location of the lesion in the nervous system was
      based on previously established criteria by using clinical and complementary
      studies. RESULTS: Of the 27 patients included in the study we were able to reach
      an accurate topographical diagnosis in 9. None had an exclusive involvement of
      the peripheral nervous system, (6) had exclusively central nervous system
      involvement and 2 showed involvement of both system. In 12, the topographical
      location of the lesion could be only ascertained as probable; 3 of them in the
      peripheral nervous system, 2 in the central nervous system and mixed involvement
      in 7. In the remaining 7 patients there were insufficient clinical data to allow
      topographical classification. CONCLUSIONS: The ophtalmoplegia-ataxia-areflexia
      syndrome can also be found in pediatric patients. The lesion in the majority of
      patients in this age group is located in the central nervous system, either alone
      or combined with peripheral nervous system involvement.

PMID- 9656535
TI  - [Juvenile spondyloarthropathies: descriptive study of 40 patients].
AB  - OBJECTIVE: The objective of this study was to describe the clinical
      characteristics of children with spondyloarthropathies diagnosed in our unit.
      PATIENTS AND METHODS: We analyzed the patients with SEA syndrome,
      undifferentiated spondyloarthropathy, psoriatic arthritis, arthritis associated
      with inflammatory bowel disease and reactive arthritis with onset symptoms before
      the age of 16. RESULTS: Forty patients were diagnoses as suffering from
      spondyloarthropathy (29 boys and 11 girls). Eight presented a SEA syndrome, 8
      undifferentiated spondyloarthropathy, 8 psoriatic arthritis, 6 arthritis
      associated with inflammatory bowel disease and 10 with reactive arthritis. No
      patient met ankylosing spondylitis criteria. In ten children the initial
      diagnosis was chronic juvenile arthritis. The articular disease had a relapsing
      and remitting course in one third of the patients. Almost 50% had only one
      episode and 7 patients had one prolonged course. In general, the functional
      outcome was good. CONCLUSIONS: Juvenile spondyloarthropathies are a group of
      rheumatic diseases with common clinical characteristics and differ from chronic
      juvenile arthritis. Their early recognition is important with regard to treatment
      and prognosis.

PMID- 9656536
TI  - [Bacterial meningitis in pediatrics. Study of 166 cases].
AB  - OBJECTIVE: The purpose of this study was to evaluate the clinical and
      epidemiological characteristics of meningitis in our environment. PATIENTS AND
      METHODS: A retrospective study of 166 cases of meningitis diagnosed in our
      hospital during a 10 year period (1986-1995) was performed. The patients were
      between 1 month and 14 years of age. RESULTS: Sixty-six percent of the patients
      were male and 34% female. Eleven cases were younger than 2 months (6.6%), 122
      cases (73.5%) were between 3 months and 5 years of age and 33 cases (19.9%) were
      older than 5 years. The most frequent symptoms and signs were fever (96%),
      vomiting (60%), impairment of consciousness (24%) and meningeal signs (49%). CSF
      cultures were positive in 52% and blood cultures in 32%. The pathogen isolated
      was N. meningitidis in 53 cases (32%), H. influenzae in 38 (23%), S. pneumoniae
      in 9 patients (5%) and others in 3 children (2%). Meningitis due to H. influenzae
      increased each year. No microorganism was isolated in blood and CSF in 63 cases
      (38%). Meningitis in children between 3 months and 5 years of age was due to N.
      meningitidis in 40 children (33%) and H. influenzae in 36 (29%). The mortality
      rate was 3%. The most frequent complications were sepsis (36%) and seizures
      (16%). CONCLUSIONS: The most frequently isolated agent in our study was N.
      meningitis. Meningitis due to H. influenzae is increasing such that H. influenzae
      and N. meningitis currently show similar frequency in children between 3 months
      and 5 years of age.

PMID- 9656537
TI  - [Frequency and current clinical diversity of cerebral cortical dysgenesis].
AB  - OBJECTIVE: The extended use of MRI has increased the number of patients diagnosed
      of cortical dysgenesis and has changed the clinical spectrum usually associated
      with this disorder. The aim of this study was to know the frequency and clinical
      variety of cortical dysgenesis in our current patient population. PATIENTS AND
      METHODS: All patients with dysgenesis of the neocortex or of the hippocampus,
      according to radiological or pathological features, were selected from the total
      number of patients attended during 1996 at an outpatient hospital-based
      neuropediatric clinic. Malformations of cerebellar cortex and neurocutaneous
      syndrome were excluded. RESULTS: Twenty-one patients (1.3% of all patients
      attended at the clinic) studied by MRI showed polymicrogyria (43%) which was of
      perisilvian localization in three patients, heterotopias (33%), dysplasia of the
      hippocampus (24%), agyria-pachygria (14%) and hemimegaencephalia (5%). Three
      patients underwent surgical interventions. Epilepsy was present in 90%, mental
      retardation in 68%, cerebral palsy 47%, infantile spasms 40%, microcephally 25%,
      autism 10%, hyperkinesis 5% and learning disabilities in 33% of those school age
      children free of mental retardation. CONCLUSIONS: The actual prevalence of
      cortical dysgenesis at our clinic is similar to that of neurodevelopmental
      impairments following birth-asphyxia (1.2%), amounting to two thirds of those
      following prematurity and to half of those following a brain injury of late
      prenatal onset. Except for the almost constant presence of epilepsy, especially
      infantile spasms, clinical symptomatology is diverse and occurs in a similar
      percentages in brain lesions acquired during labour or during late pregnancy.
      Hyperkinesis and autism have a similar prevalence to that seen in the total
      number of patients attended at the clinic during 1996.

PMID- 9656538
TI  - [Secondary effects of prostaglandin E1 on the management of hypoplastic left
      heart syndrome while waiting for heart transplantation].
AB  - OBJECTIVE: Newborns with hypoplastic left heart syndrome (HLHS) included in the
      heart transplant program depend on continuous prostaglandin E1 (PGE1) perfusion
      for a prolonged period of time, which can result in various side effects. The
      objective of this study was to analyze the side effects derived from the use of
      PGE1 in newborns with HLHS who are awaiting heart transplantation. PATIENTS AND
      METHODS: Fifteen newborns with HLHS included in a cardiac transplant program
      between January 1993 and August 1996 were studied. All received continuous
      endovenous perfusion of PGE1 from the time of diagnosis of the cardiopathy.
      RESULTS: Thirteen patients were transplanted, with 6 dying in the operating room.
      Seven survived. Two patients died while waiting for a transplant. All presented
      short term side effects derived from the continuous perfusion of PGE1, including
      a slight fever and irritability. However, none of them presented apnea pauses.
      Cortical hyperostosis and anthral hyperplasia were observed in 13 (83.3%) and 12
      (80%) cases, respectively, but in all transplanted cases regression of the
      anthral hyperplasia was seen after 6 months and regression of the cortical
      hyperostosis was seen after 12 months. CONCLUSIONS: PGE1 was effective in
      maintaining the permeability of the ductus arteriosus. The side effects derived
      from the treatment were well tolerated. The appearance of cortical hyperostosis
      and anthral hyperplasia is related to the duration of the perfusion and these
      disappear in the weeks following the suspension of PGE1 treatment.

PMID- 9656539
TI  - [Jarcho-Levin and Casamassima syndromes: differential diagnosis and frequency in
      Spain].
AB  - OBJECTIVE: Jarcho-Levin syndrome is characterized by the presence of only costal
      vertebral defects. However, this diagnosis has been used in any case presenting
      with costovertebral defects, whether associated to other congenital defects or
      not. Recently, it has been demonstrated that costovertebral defects constitute a
      developmental field defect and, because of this, they can be observed in
      different clinical and etiological patterns. On the other hand, Casamassima
      syndrome is characterized by the presence of costovertebral defects, genito
      urinary anomalies and anal atresia, which make it easily distinguishable from
      Jarcho-Levin syndrome. PATIENTS AND METHODS: We present the cases with Jarcho
      Levin and Casamassima syndromes identified among 1,405,374 liveborn (LB) infants
      registered by the Spanish Collaborative Study of Congenital Malformations
      (ECEMC). RESULTS: Frequencies of these two syndromes in the ECEMC are 0.2 per
      100,000 LB for Jarcho-Levin syndrome and 0.3 per 100,000 LB for Casamassima
      syndrome. We present the clinical manifestations and other characteristics of all
      the cases registered with these syndromes in the ECEMC. CONCLUSIONS: Jarcho-Levin
      syndrome is defined by the presence of costoveriebral defects without any other
      congenital defect. However, given that the alterations of the axial skeleton are
      a developmental field defect, they can be observed in different clinical
      etiological patterns that should not be considered as Jarcho-Levin syndrome.
      Among these, Cassamassima syndrome can be clearly distinguished, being autosomal
      recessive as is Jarcho-Levin syndrome.

PMID- 9656540
TI  - [Absorptive pattern of individual fatty acids and total fat in full term babies.
      Its stability in the absence of lactose].
AB  - OBJECTIVE: Lactose absence implies a decrease in calcium absorption. If not
      absorbed, calcium soaps can be produced with the intestinal fatty acids.
      Absorption and retention of total fat, individual fatty acids, calcium, magnesium
      and phosphate have been compared between two groups of children, one fed with
      lactose free formula and higher levels of calcium (FSL) and the other with
      standard starting formula (FI). None of them had additional arachidonic or
      docosahexaenoic acids. PATIENTS AND METHODS: A randomized prospective study was
      made on 19 term newborn babies by means of metabolic balance measurement during
      an 8 day period (four days of a stabilization period on the formula, 3 days of
      the balance period and the final day for feces collection). Both groups were
      selected following the same criteria for gestational age, balance age, and weight
      and length at both time periods. Aliquos from the formula were collected daily,
      as well as all feces and urine during the balance period. Calcium and magnesium
      quantification of the corresponding ashed products was performed by means of
      atomic absorption, while Pi was with a colorimetric assay. Total fat was
      extracted by organic solvents and quantified by gravimetry. Lipid phase fatty
      acids were methylated, extracted and quantified by means of gas chromatography
      with a detector of flame ionization. RESULTS: Total fat content and the
      percentages of each fatty acid did not differ, only calcium concentration in FSL
      was slightly higher (64.9 +/- 6.9 vs 58.9 +/- 7.0 mg/100 g). No differences were
      found between groups in relation to ingestion, excretion and retention. The
      percentages of calcium and total fat retention, however, were slightly superior
      in the FI in relation to the FSL group. Ca: 68 +/- 22 mg/kg/d, 49 +/- 14% vs 56
      +/- 23 mg/kg/d, 48 +/- 17% and total fat: 6.6 +/- 1.2 g/kg/d, 92 +/- 8% vs 6.8 +/
      1.5 g/kg/d, 90 +/- 9%. Absorption of MC fatty acids was 99% for C8. Linoleic and
      alfalinolenic acid showed an absorption of around 90% despite the big differences
      in their intake (10/1). Net retention of linoleic acid was 933 +/- 168 mg/kg/d
      (FI) and 963 +/- 190 mg/kg/d (FSL) and the amount of alpha-linolenic acid was 95
      +/- 16 (FI) and 100 +/- 22 mg/kg/d (FSL). No correlation could be found between
      the amount of excreted calcium and the total amount of fat in feces or with any
      of the fatty acids studied. This was true for each group studied separately or
      when considered as a single group. CONCLUSIONS: The absorptive pattern of fatty
      acids in full term babies, when quantified did not show any conspicous
      alterations in relation to the accepted values of other ages. The absence of
      lactose (FSL) in a formula does not make any change in the absorption of total
      fat and the individual fatty acids when compared to lactose containing formula
      (FI), when these are present in the same proportions. Supplemented calcium in the
      formula without lactose could compensate for its lower absorbtion. The absorptive
      pattern of fatty acid in full term babies did not show any conspicuos alterations
      in relationship to the accepted values of other ages.

PMID- 9656541
TI  - [Syringomyelia, Chiari's malformation and scoliosis in a patient with type 1
      neurofibromatosis].

PMID- 9656542
TI  - [Multidisciplinary treatment without major plastic surgery of complicated
      neonatal postoperative mediastinitis].

PMID- 9656543
TI  - [Mounier Kuhn syndrome: clinical course of a case in childhood].

PMID- 9656544
TI  - [Congenital cutis marmorata telangiectatica. Report of a new case].

PMID- 9656545
TI  - [Electric burns of the mouth. Their impact in childhood].

PMID- 9656546
TI  - [Hypertransaminasemia as first manifestation of celiac disease].

PMID- 9656547
TI  - [Subcutaneous nodules in a newborn child].

PMID- 9656548
TI  - [Acute pain, analgesia, and sedation in children (IIIb): pharmacokinetics and
      pharmacodynamics of sedatives].

PMID- 9656549
TI  - [Study of pediatric massage].

PMID- 9656550
TI  - [Research training in the postgraduate period].

PMID- 9656551
TI  - [Kinetics of in vitro clonal growth of the murine MB-49 bladder tumor cell line].
AB  - OBJECTIVE: To analyze the in vitro growth kinetics of the MB-49 murine bladder
      tumor cell line. METHODS: Cell proliferation and duplication time (DT) were
      determined by 595 nm absorbance analysis and hemocytometry with and without fetal
      calf serum (FCS). RESULTS: The 595 nm absorbance and the hemocytometer cell count
      correlated according to the linear equation of cell number = 595 nm absorbance x
      334.110-8.795 (r = 0.98). Cell proliferation was significantly higher in cultures
      with FCS (p < 0.001). However, a significant increase in the cell count (p <
      0.01) was observed after 24 hours in cultures with and without FCS. DT was 21 and
      50 hours for cultures with and without FCS, respectively. CONCLUSION: This
      experiment confirms the nature of the tumor cells and permits establishing the
      precise growth conditions of the MB-49 cells in this laboratory.

PMID- 9656552
TI  - [Reduction of hospital stay, because of the early removal of the bladder catheter
      in transurethral resection of the prostate].
AB  - OBJECTIVE: To analyze the effects of removal of the bladder catheter 48 hours
      following transurethral resection of the prostate for benign prostatic
      hyperplasia in relation to the length of hospital stay and the incidence of
      important postoperative complications. METHODS: A study was conducted on 117
      patients who had undergone TURP at our hospital over a period of one year. They
      were divided into two groups: group I comprised 55 patients in whom the bladder
      catheter had been systematically removed 48 hours following the procedure and had
      been discharged from hospital once they had attained a satisfactory micturition;
      group II comprised 62 patients in whom the bladder catheter was removed following
      conventional practice. RESULTS: The mean length of hospital stay for the early
      catheter removal group was 2.02 days versus 3.85 days for group II. The
      postoperative complication rate was similar for both groups. CONCLUSIONS: Early
      removal of the bladder catheter following TURP does not increase the complication
      rate. It shortens the length of hospital stay and reduces the cost of the
      procedure.

PMID- 9656553
TI  - [Mumps orchitis; review of 8 cases].
AB  - OBJECTIVE: To determine the incidence of mumps orchitis in young males in the
      area of El Bierzo (Ponferrada, Spain) and the complications arising from this
      condition. METHODS: The cases of mumps orchitis referred by the primary care
      services to the emergency services of Hospital del Bierzo referral center were
      reviewed. We analyzed patient age, unilateral or bilateral testicular
      involvement, whether the patients had been vaccinated against mumps and the
      changes observed in the semen analysis. RESULTS: The diagnosis of mumps orchitis
      was confirmed in 8 patients, aged 15 to 19 years. Two patients had bilateral
      testicular involvement. Seven patients had not been vaccinated against
      parotiditis. Three patients had oligoasthenospermia and are currently being
      followed at the Urology services. CONCLUSIONS: The utility of large scale
      vaccination against mumps is emphasized. Long-term follow-up is recommended for
      all patients with abnormal semen analysis, particularly those with bilateral
      testicular involvement, since they may develop oligoasthernospermia several years
      after the infection or improve with item. A high incidence of mumps orchitis was
      found for this 12-month study period.

PMID- 9656554
TI  - [Ureteral bladder augmentation. Report of 5 cases].
AB  - OBJECTIVES: To describe 5 cases of ureteral bladder augmentation. METHODS: From
      may 1995 to september 1997, ureterocystoplasty was performed on 5 patients (3
      males and 2 females), aged 2 to 18 years (mean 9.8). The mean follow-up was 16.6
      months (range 4-28). RESULTS/CONCLUSION: Augmentation ureterocystoplasty has the
      beneficial effects of enterocystoplasty without the complications that may arise
      from the use of bowel segments. It is a simple surgical technique whose outcome
      depends entirely on careful patient selection.

PMID- 9656555
TI  - [Abdominal pain in patients undergoing radical cystectomy for bladder cancer].
AB  - OBJECTIVE: To analyze the incidence and causes of emergency admission for
      abdominal pain in patients submitted to radical cystectomy for bladder cancer.
      METHODS: A retrospective study was conducted on 176 patients who had undergone
      radical cystectomy for bladder cancer. The preoperative treatment, urinary
      diversion procedure, postoperative tumor stage, complications and adjuvant
      treatment required were analyzed. The patients had a follow-up of 43.7-58.3
      months (mean 51). RESULTS: 18 patients required admission for abdominal pain; 7
      for complete bowel obstruction, 5 for partial obstruction of the intestine and 6
      for intestinal fistula (4 to the neobladder, 1 to the urethra, and 1 to the
      vagina). In 6 patients abdominal pain was caused by recurrence of a pelvic tumor.
      Seven patients required emergency surgery and 5 elective surgery. CONCLUSIONS:
      10.5% of the patients who had undergone radical cystectomy for bladder cancer had
      at least one episode of abdominal pain requiring admission to hospital. During
      the first 6 months postoperatively, partial obstruction of the intestine was the
      most common cause of abdominal pain, and thereafter, complete bowel obstruction
      and intestinal fistula to the neobladder. Abdominal pain was caused by recurrence
      of a pelvic tumor in 33% of the patients and by a benign condition in the
      remaining patients. We found no risk factors related with the preoperative
      treatment, tumor, urinary diversion procedure or early complications that may
      predispose to episodes of abdominal pain.

PMID- 9656556
TI  - [Incidence and risk factors for calculi formation in patients treated with
      augmentation cystoplasty or intestinal substitution].
AB  - OBJECTIVE: Bladder stones have been observed more frequently in patients
      undergoing bladder augmentation or substitution than in the normal population. We
      analyzed the etiological factors influencing bladder stone formation in patients
      submitted to the foregoing procedures. METHODS: Between December 1986 and October
      1994, 12 augmentation cystoplasties with detubularized ileum or colon (group I)
      and 24 substitution ileocystoplasties (group II) were performed. None of the
      patients were known to have urinary stone formation. The possible causes of
      bladder stone formation were analyzed in both patients groups. The patients were
      evaluated for urinary infection, post micturition bladder residue, urinary pH,
      and stone forming metabolic alterations in blood or urine. The latter consisted
      in determining the blood levels of creatinine, calcium, uric acid and phosphorus
      and the 24-hr urine levels of calcium uric acid, phosphorus, creatinine, urea,
      oxalic acidi citric acid and magnesium. The statistical analysis consisted of an
      unweighted logistic regression test and a chi square test between each of the
      above variables and the existence of bladder stones. RESULTS: In group I, 10
      patients revealed recurrent urinary infections, 0 showed a significant post
      micturition bladder residue, a pathologically alkaline pH was observed in 2 and
      the metabolic study of blood and urine revealed alterations in 9 patients. In
      group II, 18 patients revealed recurrent urinary infection, 13 patients had post
      micturition bladder residue, a pathologically alkaline pH was observed in 1, and
      the metabolic study of blood and urine revealed alterations in 13 patients. The
      statistical analysis using the unweighted logistic regression test showed no
      significant relation between any of the parameters and the presence of stones,
      for the substitution group pr augmentation group. However, the chi-square test to
      determine the relation between the different varikables and the existence of
      stones, showed a statistically significant relation between an elevated urinary
      pH, recurrent urinary infection, post-micturition bladder residue and bladder
      stone formation for groups I. Concerning the type of suture employed, some degree
      of relation between the use of non-resorbable suture and stone formation was
      found, although it was not statistically significant. CONCLUSION: We can
      therefore conclude that urinary pH, recurrent urinary infection annd post
      micturition bladder residue, and probably use of nonreabsorbable suture, are
      among the etiological factors that we should avoid and treat in order to prevent
      the formation of bladder stones in patients undergoing augmentation or
      substitution cystoplasty.

PMID- 9656557
TI  - [Which treatment should children with recurrent urinary infections, without
      anatomical anomalies, receive?].
AB  - OBJECTIVE: To determine the best treatment for children with recurrent infection
      of the lower urinary tract and without anatomical abnormalities. METHODS: A
      clinical study was conducted on 150 children (30 boys and 120 girls), aged 4 to
      36 months (mean 16), with recurrent urinary tract infections (UTI) and no
      radiological evidence of anatomical abnormalities. They were divided into three
      groups: group I was treated with a single nightly prophylactic dose of an
      antibiotic; group II received a single nightly dose of oxybutinin, or divided in
      2-4 doses; group III received a single nightly prophylactic dose of an antibiotic
      and oxybutinin as in group II. RESULTS: There were more episodes of UTI in group
      I (44/50), more hospitalizations and problems of malnutrition, and a longer
      period of treatment was required. In group II, 14/50 children had episodes of
      UTI, their nutritional status improved and there were less hospitalizations. In
      group III, 3/50 children had episodes of UTI; they were the best responders and
      required a shorter duration of treatment. CONCLUSIONS: Prophylactic therapy
      requires a longer period of treatment. The use of oxybutinin is an alternative
      modality in the treatment of these children. Combination therapy with a single
      nightly dose of an antibiotic and anticholinergic (oxybutinin) appears to be the
      best therapeutic modality for children with recurrent UTI and no anatomical
      abnormality.

PMID- 9656558
TI  - [Double J ureteral catheter. Clinical complications].
AB  - OBJECTIVE: To analyze the clinical complications of double-J ureteral catheters.
      METHODS: The most relevant studies published in the literature since the self
      retaining indwelling catheter was first described in 1967 are reviewed. RESULTS:
      The experience and results reported in the most relevant studies are presented.
      CONCLUSIONS: The double-J ureteral stent has become an integral part of the
      urological armamentarium. It allows good urinary drainage from the kidney to the
      bladder and is generally safe and well-tolerated. However, different
      complications may occur with short- or long-term use of indwelling stents. These
      complications vary from minor side effects such as hematuria, dysuria, frequency,
      flank and suprapubic pain, to major complications such as vesico-ureteric reflux,
      stent migration, encrustation, urinary infection, stent fracture, necrosis and
      ureteral fistula. Most of these complications require removal of the catheter.

PMID- 9656559
TI  - [Urologic iatrogenic disease].
AB  - OBJECTIVE: The purpose of this paper is to emphasize that despite the undeniable
      advantages of urological instrumentation (insertion of a ureteral catheter,
      double-J catheter; percutaneous nephrostomy, etc.), it also carries some risks
      and complications. METHODS: We report three cases of iatrogenic urological
      complications due to use of endoscopic and percutaneous material.
      RESULTS/CONCLUSION: Urologists, and particularly the residents, are reminded that
      iatrogenic complications may occur even in the easiest and routine procedures of
      the medical activity.

PMID- 9656560
TI  - [Adrenal gland myelolipoma: review of the bibliography regarding a case].
AB  - OBJECTIVE: To describe an additional case of this rare disease entity, with
      special reference to its diagnosis and treatment, and to briefly review the
      literature. METHODS: We report on an 82-year-old male with adrenal myelolipoma
      that had been incidentally discovered during evaluation for another condition. A
      left adrenalectomy was performed due to the large size of the tumor and in order
      to determine its benign or malignant nature. RESULTS: The histopathological
      findings disclosed an andrenal myelolipoma. CONCLUSIONS: Adrenal myelolipoma is
      an uncommon tumor type. CT is the most effective diagnostic method. Surgery is
      advocated in symptomatic cases and in asymptomatic cases with a large tumor mass.

PMID- 9656561
TI  - [Condylomata acuminata in childhood: report of a case].
AB  - OBJECTIVE: To report an additional case of condylomata acuminata in a child,
      review the literature and discuss the medicolegal implications due to the
      possibility of sexual abuse. METHODS/RESULTS: The diagnosis, treatment and
      clinical course of the lesions are discussed. Psychological evaluation of the
      child discarded infection by sexual transmission. CONCLUSION: Condylomata
      acuminata in children represent a diagnostic difficulty due to the possibility of
      infection by sexual transmission, although it should be taken into account that
      non sexual transmission of this sexually transmissible disease is very frequent
      in childhood.

PMID- 9656562
TI  - [Pyelocaliceal urothelial carcinoma associated with pelvis lithiasis].
AB  - OBJECTIVE: Epithelial neoplasms of the upper collecting system account for less
      than 5 percent of all urothelial tumors and they are not histologically unlike
      those of the bladder. We report a case of pelviocaliceal urothelial carcinoma
      associated with a calculus in the renal pelvis. METHODS: A 75-year-old man who
      presented with hematuria, fever and flank pain is described. The US and CT
      findings disclosed a calculus in the left renal pelvis and hydronephrosis
      nephrectomy was performed. RESULTS: The pathological analysis revealed a
      pelviocaliceal urothelial carcinoma on an underlying stone and overexpression of
      the p53 protein. CONCLUSION: Diagnostic imaging techniques may fail to detect
      tumors of the renal pelvis with a large underlying stone. The overexpression of
      the p53 protein may be involved in the malignant transformation of the urothelial
      cells.

PMID- 9656563
TI  - [Conservative treatment of microcytic carcinoma of the bladder; report of a new
      case].
AB  - OBJECTIVE: To report an additional case of small cell carcinoma treated
      conservatively. METHODS: Herein we describe a case of small cell carcinoma of the
      bladder that had been treated conservatively because of the age of the patient.
      The specific characteristics of the case are described and the clinical and
      pathological aspects of the disease are briefly reviewed. RESULTS/CONCLUSION:
      Although treatment of this disease is primarily by cystectomy followed by chemo
      and radiotherapy, organ-sparing neoadjuvant chemo and radiotherapy as an
      alternative to surgery could be attempted to obtain complete remission in
      selected patients.

PMID- 9656564
TI  - [Extra-adrenal retroperitoneal paraganglioma].
AB  - OBJECTIVE: To report a case of paraganglioma localized in the organ of
      Zuckerkandl and to discuss its diagnosis, treatment and outcome. METHODS/RESULTS:
      A 37-year-old female presented with a periumbilical mass and pain that radiated
      to the lumbar region for the past three months. Abdominal US and CT disclosed a
      well vascularized mass lying adjacent to the aorta, 1 cm from its bifurcation. At
      laparotomy, an 8 x 10 cm tumor was discovered at the aortic bifurcation that
      displaced the left ureter and included the inferior mesenteric artery.
      Pathological analysis of the surgical specimen revealed a paraganglioma.
      CONCLUSION: Extra-adrenal paraganglioma should be taken into account in the
      differential diagnosis of retroperitoneal masses, particularly those adjoining
      the abdominal aorta.

PMID- 9656565
TI  - [Hematuria, dysuria, pollakiuria and general malaise, in a patient treated with
      BCG instillations].
AB  - OBJECTIVE: To report a case of granulomatous cystitis in a patient receiving
      bacillus Calmette-Guerin intravesical therapy for urothelial carcinoma in situ.
      METHODS: A 58-year-old man undergoing BCG intravesical therapy for urothelial
      carcinoma in situ presented symptoms of intense cystitis. Cystoscopy was
      performed and several bladder cold biopsies were obtained. RESULTS:
      Histopathological analysis demonstrated epithelioid granulomas. CONCLUSION:
      Cystitis arising from BCG therapy is defined as drug-induced or BCG-induced
      cystitis. Intense cystitis and malaise are a serious complication since it is not
      possible to distinguish patients with a simple uncomplicated local reaction from
      those who will develop progressive systemic infection. Cystoscopy and biopsy can
      be helpful in determining the nature of the condition and are recommended.

PMID- 9656566
TI  - [Re: Testicular infarction, simulating a neoplasm].

PMID- 9656567
TI  - The role of in vitro chemosensitivity tests to predict the clinical efficacy of
      antineoplastic agents in genito-urinary tumors.
AB  - OBJECTIVE: To develop an in vitro screening system to predict the response to
      treatment of common malignancies of the genito-urinary tract. MATERIAL AND
      METHODS: Flow cytometric analysis and cytotoxicity assays (trypan blue and lactic
      dehydrogenase colorimetric tests) were performed on hormone resistant prostate
      cancer cell line PC-3 and primary transitional cell carcinoma samples treated
      with different antineoplastic agents and their combinations. Apoptosis induced by
      different agents was also investigated by previously established criteria.
      RESULTS: There were 9 bladder tumors (47.4%) in the study group that displayed
      drug resistance to at least one antineoplastic agent. When the drugs were
      examined individually, there was resistance to cis-platinum in 3 patients
      (15.8%), methotrexate in 6 (31.6%), vinblastine in 7 (36.8%), epirubicin in 2 and
      adriamycin in 2 patients (10.5%). Stratification of patients according to the
      stage of the tumor revealed statistically significant difference between the
      superficial and invasive tumors in terms of drug resistance (p < 0.05). In
      prostate cancer cell line vinblastine treatment resulted in a significant
      increase in S phase fraction. Percent cytotoxicity by trypan blue exclusion test
      was 26.1% and was significantly higher than the control group (8.7%, p < 0.002).
      Also, an increase in apoptotic index after the treatment was observed (44.4% and
      12.1%, respectively; p < 0.0001). CONCLUSION: Both toxicity assays showed a very
      good correlation (p < 0.005) and can be used to evaluate the effects of different
      antineoplastic agents on individual tumors.

PMID- 9656568
TI  - [Recent research for the development of anti-allergic agents--an approach for the
      regulation of allergic functional molecule].

PMID- 9656569
TI  - [Progress in cell biology on eosinophils].

PMID- 9656570
TI  - [Analysis of inspiratory flow-volume curve].
AB  - Inhaled antiasthmatic agents can be effective, but their efficacy depends on the
      delivery system and on inhalation technique, especially in metered-dose inhalers
      (MDI). To find out whether inhalation therapy for asthmatics had been performed
      correctly, we studied inspiratory flow in the slow matter in healthy subjects and
      bronchial asthma patients. About half of 30 patients studied inspired more than 1
      L/sec inspiratory flow rate, especially in male. Inspiratory flow in the fast
      matter (peak inspiratory flow; PIF) is important in the use of dry powder
      inhaler, so we studied the correlationship between PIF and expiratory flow and
      volume parameters. PIF correlated with PEFR, FEV1 and FEV1% in female, FVC and
      %FVC in male, respectively. In summary, we must recognize slow inspiratory flow
      can not be gotten easily, and asthmatic patients always have to use MDI carefully
      in inspiratory flow. Some expiratory parameters of spirometry can accurately
      predict PIF. The analysis of inspiratory flow-volume curve gives us beneficial
      data in inhalation therapy.

PMID- 9656571
TI  - [A new device for allergen skin testing].
AB  - We have made a new device for allergen skin testing, which can be used easily. It
      consists of two parts. One, several gears are fixed on a board in a row, and when
      one gear goes round, other gears also go round simultaneously. A disposable
      needle is attached to each gear. A semi-spherical hole is made in the lower
      surface of a disposable needle, and a sharp needle is fixed in, but not at the
      centre of the hole. The other, small tanks are arranged in a row at the same
      distance as the gears. When the disposable needles are inserted to the tanks
      filled with allergen extract, it is hold in a semi-spherical hole by surface
      tension. The allergen extracts go intradermally, when the needles move semi
      circular on a human skin. We performed skin tests to 23 patients with this
      device, and got satisfactory results as screening tests.

PMID- 9656572
TI  - [Isoproterenol continuous nebulization for childhood status asthmaticus. I.
      Efficacy and side effects of high-dose method].
AB  - We investigated the efficacy and the side effects of "high-dose isoproterenol
      continuous nebulization" for childhood status asthmaticus. Subjects were 34
      children who were hospitalized and underwent the nebulization therapy. The 50 ml
      solution of 0.5% dl-isoproterenol was diluted in 500 ml of normal saline and
      nebulized through an ultrasound nebulizer. The period of continuous nebulization
      was 25.5 +/- 16.0 hours. The Wood's clinical score clearly decreased in 32 cases,
      the average score changing from 7.7 +/- 0.8 to 2.9 +/- 1.3. Heart rate was
      elevated significantly during the first 3 hours (156 +/- 25/min at the start of
      the nebulization, 180 +/- 20/min at 1 hour, 171 +/- 23 at 3 hours), and then it
      decreased gradually to 122 +/- 25/min at the cessation of the nebulization. Serum
      GOT, LDH, CPK, and potassium were elevated after the nebulization compared with
      the values before the treatment, though the changes were not statistically
      significant. CPK-MB fraction after the nebulization was higher than normal range
      in 12 of 13 subjects. Of 34 subjects, 11 (32%) complained nausea or vomited, 2
      showed arrhythmia on ECG (ventricular premature conduction), 1 developed
      myocardiac infarction, and 1 developed possible heart failure, some of which
      might be attributable to the pharmacological side effects of isoproterenol
      nebulization. We conclude that "high-dose isoproterenol continuous nebulization"
      is an effective method for childhood status asthmaticus, but there is some risk
      of serious side effects. This method was originally developed as a method
      indicated for the case of respiratory failure or threatened respiratory failure
      following status asthmaticus, and we should not extend the indication of this
      method thoughness.

PMID- 9656573
TI  - [Allergen-induced cytokine messenger RNA expression of peripheral blood
      mononuclear cells in active and remission of food allergy].
AB  - Substantial part of patients who suffer from food allergy outgrow their allergic
      reaction. Moreover the mechanisms of this phenomenon are poorly understood. We
      studied cytokine mRNA expression in peripheral blood mononuclear cells (PBMC)
      from children with egg allergy, nine patients on active stage and eight were
      outgrown, and four healthy controls, by use of reverse transcription polymerase
      chain reaction. Following ovalbumin (OVA) stimulation in vitro, active patients
      demonstrated increasing IL-5 mRNA. In comparison, no increasing expression of IL
      5 mRNA was observed in outgrown and healthy children. IL-4 and IFN-gamma mRNA
      expression has no tendency either to increase or to decrease in all three groups.
      There was no difference of proliferative responses for OVA among these groups
      suggesting that outgrown patients' PBMC did not fall into anergy or clonal
      deletion. These data suggested the change in balance of cytokine production of
      PBMC which were stimulated by allergen is a trigger for "outgrow" of food
      allergy.

PMID- 9656574
TI  - [Theophylline reduces serum levels of ECP in vitro].
AB  - Measurement of serum levels of ECP has been widely used for monitoring airway
      inflammation in bronchial asthma and recently been applied to measure anti
      inflammatory effect of theophylline. However, reduced levels of ECP in
      theophylline-administered patients may express not only in vivo effect of
      theophylline but also in vitro effect after sampling because serum ECP measures
      released ECP during coagulation and theophylline has been reported to inhibit
      eosinophil degranulation in vitro. In order to answer the question, we tested
      whether theophylline added to blood after sampling reduces measured levels of
      serum ECP. Various concentrations of theophylline were added to SST tube, to
      which venous blood from atopic patients was drawn. Serum was, then, obtained by
      centrifugation after 15 min to 6 hours of incubation at room temperature.
      Theophylline significantly reduced serum ECP in a concentration-dependent manner.
      Percent reduction of ECP levels at 1 hour of incubation were 11.9%, 18.7%, 22.8%,
      and 51.7% at theophylline levels of 5, 12.5, 22.5, and 120 micrograms/ml,
      respectively. Kinetics of serum ECP release was also inhibited in the presence of
      theophylline. These results suggest that in vitro effect of theophylline on serum
      ECP levels should be considered when data of serum ECP in patients who take
      theophylline are interpreted.

PMID- 9656575
TI  - [Effects of institutional therapy and factors which influence the prognosis].
AB  - We examined the effect of institutional therapy on asthmatic children and
      evaluating the factors influencing the prognosis. We analyzed the questionnaires
      and laboratory findings obtained form the 565 children who had been treated with
      the therapy in National Higashi-Saitama Hospital from April 1978 to March 1997.
      The institutional therapy seems to be effective in the following 3 aspects. 1)
      Pulmonary function test such as FEV1.0, and bronchial hypersensitivity test such
      as acetylcholine inhalation test were improved. 2) Exercise abilities such as
      free running were improved. 3) More than 40% of the patients had no asthma attack
      or only a few mild asthma attacks requiring no medication. When compared the
      group whose symptoms were not improved with the remission group, who had no
      asthma attack, significant differences were seen in the following points, 1) The
      dose and the number of the medicines at the end of the hospitalization, 2) the
      bronchial hypersensitivity test, 3) the age of onset, 4) the age of the symptoms
      become perennial and 5) the term from the symptoms become perennial to the
      hospitalization were significantly different. The therapy principles including
      the recipes for exercise training were not different between the two groups. It
      is concluded that we should consider institutional therapy or, a combination of
      physical training and environmental control as one of the most important
      therepeutic methods when asthmatic symptoms become perennial in spite of the
      conventional medication.

PMID- 9656576
TI  - [BCG-induced T cell anergy and its activation by IL-4].
AB  - In response to stimulation with immobilized anti-CD3 antibody, splenocytes from
      C57BL/6 and BALB/c mice principally produced INF-gamma and IL-4, respectively.
      However, both splenocytes equally proliferated in response to ConA. We compared
      the changes after inoculation with BCG (1 mg/mouse) in their capacity to produce
      IL-4 or IFN-gamma in response to anti-CD3 antibody and to proliferate in response
      to ConA. Splenocytes from C57BL/6 and BALB/c mice, that had been inoculated with
      BCG 4 weeks before, produced IFN-gamma with diminished IL-4 production in
      response to anti-CD3 antibody. Furthermore these splenocytes became anergic to
      ConA stimulation and died due to cell apoptosis in stead of proliferation.
      However, we observed the strain difference at 12 weeks after BCG-infection. BCG
      primed C57BL/6 splenocytes, that continuously produced IFN-gamma in response to
      anti-CD3 antibody, failed to proliferate in response to ConA. In contrast, BCG
      primed BALB/c splenocytes, that increased IL-4 production but decreased IFN-gamma
      production when stimulated with anti-CD3 antibody, could proliferate well in
      response to ConA. Since the splenocytes of BALB/c mice became ConA responsive
      along with their shifting from Th1 dominant immune response at 4 weeks to Th2
      dominant immune response at 12 weeks after BCG-inoculation, IL-4 was assumed to
      play a crucial role in activation of anergic T cells. Therefore, we stimulated
      splenocytes from both strains of mice infected with BCG 4 weeks before with ConA
      in the presence or absence of IL-4. Splenocytes from BCG-infected BALB/c mice
      showed marked proliferation, while those from BCG-infected C57BL/6 mice failed.
      We found that IL-4 protected against ConA-induced cell apoptosis in BALB/c
      splenocytes but not C57BL/6 splenocytes.

PMID- 9656578
TI  - [Bioethics in primary care: questions of confidentiality].

PMID- 9656577
TI  - [A comparison of a 3 day course with a 2 week course of oral prednisolone in
      patients with chronic asthma].
AB  - To investigate an appropriate duration of short course of a oral prednisolone
      (PSL), we compare the results of a 3 day course of PSL (3D) with those of a 2
      week course of PSL (2W) in 20 patients with chronic asthma. All subjects had been
      inhaling beclomethasone dipropionate (BDP, mean daily dose: 1325 micrograms), and
      had been self-monitoring their peak expiratory flow rate (PEF) for at least 6
      months. Mean +/- SE of the best PSL-induced PEF in 2W (2W-best) was not different
      from that in 3D (397 +/- 29 and 356 +/- 23 L/min, respectively, p = 0.26). Mean
      weekly morning PEF/2W-best before and 1, 2, 3 and 4 weeks after PSL was 60, 76,
      80, 76 and 76% in 2W, and 63, 73, 67, 67 and 65% in 3D, respectively. Both
      changes over the course of time were significant. The frequency of emergency room
      visits and/or unscheduled hospital visits was not significantly different between
      2W and 3D. However, both the frequency of use of inhaled beta 2 agonists and the
      symptom score significantly decreased only in 2W. Seven patients (35%) did not
      need additional oral PSL during the 4-week period after initiating 3D, and among
      these patients, emergency room visits and/or unscheduled hospital visits were
      completely controlled. In conclusion, although the effect of 3D was inferior than
      that of 2W, it was a sufficient duration in 35% of the patients, and thus, may be
      appropriate as a initial duration of rescue course of oral steroids.

PMID- 9656579
TI  - [Factors involved in the non-compliance of the pharmacologic treatment of
      dyslipidemia].
AB  - OBJECTIVES: To find how much non-compliance with lipid-lowering drug treatment
      there is, its causes and to describe the profile of non-compliant patients.
      DESIGN: Prospective study. SETTING: Primary Care Centres in the province of
      Alicante. PATIENTS: 107 patients under drugs treatment for lipaemic disorders and
      belonging to live General Medical practices. MEASUREMENTS AND MAIN RESULTS: To
      evaluate compliance, the method of a surprise count of pills in the patient's
      home was used. Compliant patients were defined as those with between 80 and 110%
      compliance. 46.7% were non-compliant (C.I. 37.3-56.2), with 42% under-compliant
      and 4.7% over. Forgetfulness and unawareness accounted for 68% of the reasons for
      non-compliance. Associated factors were: moderate to high cardiovascular risk (p
      = 0.03), stating that the drug treatment was followed badly (p = 0.01), less than
      a year in regular treatment (p = 0.006), monitoring lipaemia poorly (p = 0.003).
      CONCLUSIONS: Non-compliance with pharmacological treatment in patients with
      lipaemia is high. Its causes are known, as are several factors associated to non
      compliance which could be used to identify the non-complier.

PMID- 9656580
TI  - [The chronically ill at home and the impact in main caregivers].
AB  - OBJECTIVE: To analyse the repercussions that caring for chronically sick patients
      at home can have on the health of the main carers. DESIGN: A descriptive
      crossover study. SETTING: "Raval Nord" Health District, Barcelona. PATIENTS AND
      OTHER PARTICIPANTS: All the 336 chronically sick at home recorded in the home
      care programme during January to March 1996. All the 236 carers identified during
      the same period. MEASUREMENTS AND MAIN RESULTS: 75% of the patients and 72% of
      those considered the main carers answered a home questionnaire. Most of the
      chronically ill at home were women (67%), with an average age of 81 (SD, 11). 18%
      presented severe disorders in the Short Portable Mental Status Questionnaire
      (SPMSQ), test which showed a significant relationship (p < 0.0001) with less
      autonomy according to the Katz index. 36% of carers remarked physical problems
      such as repeated back-aches and lumbago. CONCLUSIONS: The most important
      disorders affecting the autonomy and mental health of chronic patients at home
      lead to increased psychological malaise in the career, especially if he/she is a
      family member.

PMID- 9656581
TI  - [Frequency, characteristics and consequences of falls in a cohort of
      institutionalized elderly patients].
AB  - OBJECTIVE: Falls in the elderly are a major problem because of their high
      morbility and mortality rates and health expenditures. However, there are few
      studies about this problem in our country. The purpose of the present study was
      to know the frequency, features and consequences of falling among
      institutionalized elders. METHODS: We carried out a prospective cohort study
      using a sample of 190 persons aged 65 years and older living in two nursing
      homes. All subjects underwent a comprehensive evaluation at the onset of the
      study. During a mean follow-up period of 310 days, all falls were recorded.
      RESULTS: There were a total of 121 falls in 72 (37.9%) subjects, twenty five of
      whom (34.7%) experienced two or more falls. The fall incidence per person-year
      was 0.75. As compared with males, females had a density ratio (DR) of 2 (1.2-3.2;
      95% confidence interval-CI). Falling was more frequent in the bedrooms and living
      rooms (43.8%). DISCUSSION: This results agree with others studies about the high
      fall incidence in the elderly and bring out new features about circumstances and
      consequences of falls.

PMID- 9656582
TI  - [Effect of the presentation of results from clinical trials on the intention to
      prescribing: relativity of the relative risk].
AB  - OBJECTIVE: To determine if the methods of reporting results of clinical trials
      affects the physician views on prescribing. DESIGN: Analysis of responses, from a
      convenience sample of primary care physicians, of one teaching exercise on
      prescribing intention which showed 5 different methods of reporting results:
      relative risk reduction (RRR), absolute risk reduction, the percent of event free
      patients, the number needed to treat (NNT) and RRR and mortality. SETTING: Curses
      of clinical management in Valencia and Barcelona. RESULTS: The willingness to
      prescribe was significantly influenced by the way in which data were presented,
      being major when they were showed as RRR and minor when mortality was added.
      CONCLUSIONS: The method of reporting trial results has an important influence on
      the prescribing intention. The reporting of clinical trial results, and their
      abstracts or citations, should be include the NNT and negative results, for
      avoiding a subjective bias of treatment effect magnification.

PMID- 9656583
TI  - [Antibiotic consumption (1993-1996) in primary care in a health area with a high
      rate of bacterial resistance].
AB  - OBJECTIVE: To analyse the consumption of antibiotics and the consumption trend
      for 1993 to 1996 in Primary Care in a health area with high rates of bacterial
      resistance. DESIGN: Comparative retrospective analysis. SETTING: Costa de Ponent
      Primary Care area, with a census of 1,158,098 inhabitants. PATIENTS: Those
      belonging to the health area who took antibiotics during the study period.
      INTERVENTIONS: Data were obtained from the records of the Catalan Health Service.
      As a measurement of consumption of various antibiotics, the daily defined dose
      (DDD)/1000 inhabitants/day (DID). RESULTS: The DID total was very high, 17,048, a
      light increase from 1993 to 1996 (+2.4%). The groups which increased were
      cephalosporins by 42.8% and macrolides by 12.2%. CONCLUSIONS: The total
      consumption of antibiotics was very high and consonant with the high rate of
      bacterial resistance detected in our area in recent years. The progressive
      consumption of the most recently introduced antibiotics was not accompanied by a
      proportionate decrease in the consumption of others. The rationalisation of
      antibiotic use and the formation of Antibiotic Policy Committees in the Primary
      Care field should be a priority public health objective.

PMID- 9656584
TI  - [Follow up programs for children in primary care: failures to keep the
      appointments].

PMID- 9656585
TI  - [Assessment of an interventional study on iodine deficiency in Burkina Faso, 1990
      1993. Direction de la Sante de la Famille (Burkina Faso)].
AB  - OBJECTIVES: To find how the urinary parameters of iodine excretion evolved in a
      community with deficiencies, after administering iodine orally and IM in two
      provinces in Burkina Faso; to recommend a national strategy to tackle iodine
      deficits. Design. A longitudinal survey before and after the iodine was given (12
      months). Descriptive analysis of the data. SETTING: Provinces of Namentenga and
      Passore in Burkina Faso. PARTICIPANTS: The general population of the two
      provinces who satisfied age-sex criteria: males from 0 to 25, females from 0-45.
      Randomised two-stage sampling. 423 people in all took part (210 in Namentenga and
      213 in Passore). INTERVENTIONS: The administration of 1 ml of iodised oil
      (Lipiodol) orally in Namentenga and IM in Passore. MEASUREMENTS AND MAIN RESULTS:
      The urinary parameters of micrograms of iodine per gr. of Creatinine, and
      micrograms of iodine per dl of urine, were used. Figures for normalisation of the
      urinary parameters 12 months after iodisation was significantly higher in Passore
      province, where iodine was administered IM. CONCLUSIONS: The intramuscular
      pathway has more longlasting effects, but the characteristics of Burkina Faso's
      health system and the feasibility of a medium or long-term intervention make it
      advisable that iodine supplements be administered orally.

PMID- 9656586
TI  - [Sexual harassment: assessment and follow-up].

PMID- 9656587
TI  - [Consensus document on the detection and treatment guidelines for diabetic
      nephropathy in Spain. Spanish Societies of Diabetes, Endocrinology, Family and
      Community Medicine, and Nephrology].

PMID- 9656588
TI  - [Generic pharmaceutical specialties: bioequivalent and interchangeable
      medications].

PMID- 9656589
TI  - [Self-management in primary care. Working Group semFYC-SEMERGEN 1996].

PMID- 9656590
TI  - [Bureaucratic activity in the consultation of the primary care physician.
      Proposals for a debureaucratization. Working Group semFYC-SEMERGEN 1996].

PMID- 9656591
TI  - [Anticoagulation/antiaggregation treatment in patients with non-rheumatoid atrial
      fibrillation].

PMID- 9656592
TI  - [Anticoagulation in atrial fibrillation: implications in primary care].

PMID- 9656593
TI  - [Postcoital treatment in primary care].

PMID- 9656594
TI  - [Vaccination against A-C meningococcal meningitis: ethics and management].

PMID- 9656595
TI  - [The place of surgery in the treatment of locally advanced rectal cancer].
AB  - We considered as local advanced rectal cancer (LARC) tumours invading the serosa
      or adherent to neighbouring organs, tumoral fistulas, histopathologically proved
      invasion of regional lymph nodes, peritoneal carcinomatosis with or without
      neoplastic ascites. Out of 146 rectal cancers submitted to surgery between 1984
      1996, 47 had LARC (19 man and 28 women aged of 19 to 88 years) developed in the
      inferior 2/3 of rectum. We performed in these cases 11 Miles operations, 12
      posterior pelvectomies, 3 Dixon resections, 16 colostomies and 5 exploratory
      laparotomies. To these were associated 4 partial cystectomies, 4 anexectomies, 4
      partial enterectomies and 2 excisions of hepatic metastasis. In 27 patients
      adjuvant or neoadjuvant therapy was associated. We registered 3 deaths, 6
      parietal infections and 1 stercoral fistula. Postoperative survival was 3-6
      months for 12 patients, 6-12 months for 13 patients, 1-2 years for 6 patients.
      After the complex treatment 6 patients were alive at 5 years. Surgery is the
      essential therapeutic act of LARC. Chemo/radiotherapy association increases the
      survival, but not significantly.

PMID- 9656596
TI  - [Repeat hepatic resections].
AB  - Five cases of iterative liver resections are presented, out of a total of 150
      hepatectomies performed between 1.01.1995-1.01.1998. The resections were carried
      out for recurrent adenoma (one case), cholangiocarcinoma (two cases),
      hepatocellular carcinoma (one case), colo-rectal cancer metastasis (one case).
      Only cases with at least one major hepatic resection were included. Re-resections
      were more difficult than the primary resection due, first of all, to the modified
      vascular anatomy. Intraoperative ultrasound permitted localization of
      intrahepatic recurrences. Iterative liver resection appears to be the best
      therapeutical choice for patients with recurrent liver tumors.

PMID- 9656597
TI  - [Late histopathological changes at the level of the residual pancreatic stump
      after cephalic duodenopancreatectomy].
AB  - In this paper the authors present a histopathological study concerning the
      restant pancreas after cephalic duodenopancreatectomy for 3 cases that had a
      lethal outcome. In this 3 cases was performed hte cephalic duodenopancreatectomy
      with Child montage. This study showed that at the level of the restant pancreas
      it develops a progressive atrophy of the exocrine pancreatic tissue.

PMID- 9656598
TI  - [Intraoperative exploratory endoscopy in surgery of the digestive tract].
AB  - The intraoperative endoscopy as a way of the range of the surgical exploration of
      the abdomen is a valuable procedure combining surgical and endoscopical
      maneuvers. It proved useful in following conditions: A. delicate surgical
      approach of the anatomical segment; B. equivocal findings of the conventional
      endoscopy; C. as a way of achieving therapeutical goals. In 56% of the cases a
      transperitoneal approach was used and in the rest of the cases a conventional
      technique. Sterilization was performed using glutaldehide 2%, 20 minutes before
      the intervention. The methods was used in 50 cases, concerning reinterventions,
      as well as primary diseases of unclear origin. Some were high-risk patients.
      Therapeutically benefit was proven in all cases.

PMID- 9656599
TI  - [A ureteral endoscopic approach--a minimally invasive method complementary to
      nephroureterectomy].
AB  - Nephroureterectomy with ureteral stump excision and perimeatal cystectomy is the
      "golden standard surgical approach" for urothelial upper urinary tract cancer.
      Nephroureterectomy is also necessary in renoureteral tuberculosis, with
      compromised renal unit. Since June 1995 we performed the endoscopic distal
      ureteral approach in 11 cases (9 cases with upper urinary tract cancer and 2
      cases with renal tuberculosis and concomitant ureteral distal lesions). In 7
      cases we performed ureteral stripping after nephrectomy and in 4 cases we
      performed endoscopic disconnection of the intramural ureter followed by
      nephroureterectomy (in one operative step). Ureteral stripping was realized in
      two ways: perimeatal resection of the ureter and 12 o'clock incision. There was
      only one intraoperative complication which consisted in the dislodgement of the
      ureteral catheter who needs conversion to open surgery. Mean follow-up period was
      12 months (range 2 to 28). The evolution of the patients was satisfactory, with
      significant reduction of the hospitalization. According to our experience the
      endoscopic distal ureteral approach is a safer complementary proceeding to the
      one step nephroureterectomy, being performed faster and easier than open
      ureterectomy.

PMID- 9656600
TI  - [Antroduodenoplasty (an original method) in the surgical treatment of a
      perforated duodenal ulcer].
AB  - It's present an original method in the treatment of perforated duodenal ulcer
      (antro-duodenoplasty or antro duodenal aposition). To a group of 256 patients
      with gastro-duodenal ulcer operated in the period 1985-1995, it is fancy an apply
      these method to 56 patients (21%). These method applied is simple and performed
      in any surgical service and it't not necessary a special technical organization.
      The evolution of 56 patients there is no incidents. The originality consist in
      your simplicity, but and in the fact that these method it's not communicated in
      the surgical literature of Romania or anywhere in the latest ten years.

PMID- 9656601
TI  - [Liver transplantation. II.A rapid technic for taking a liver graft in the
      context of taking multiple organs from a donor in a state of brain death].

PMID- 9656602
TI  - [Nosocomial infections in the Clinica Chirurgie CFR, Craiova].
AB  - The authors present Craiova CFR General Surgery Clinic experience on hospital
      infections from 1991 through 1996. This study shows that the frequency of
      hospital infections in our clinic is greater than all the other postoperative
      complications. Over the investigated period of time we witnessed an increase in
      the incidence of the postoperative septic complications in addition to those
      directly linked to the operated interventions (e.g. wound infections,
      postoperative peritonitis) such as: pulmonary infections: urinary tract
      infections, catheter sepsis etc. Finally, the authors pointed to the consequences
      of the hospital infections such as: mortality and late morbidity rates, economic
      implications. Thus, it is worth mentioning that 30 deaths (75%) out of our clinic
      total of 40 over the studied period of time were due to a postoperative
      infections and treatments.

PMID- 9656603
TI  - ["Combined treatment" in the liver metastases of colorectal cancer].
AB  - Patients with liver metastasis after colo-rectal cancers are, from the point of
      une of their disease evolution in the final stadium (the IV th. stadium). Hence,
      we consider the attempt for liver metastasis treatment, as being desperate
      experiments to extend the patient's life, taking high risks and having chances of
      immediate failure. Since 1995 me've started a study about patients operated for
      colo-rectal cancers that will stand transarterial chemoembolization of their
      hepatic metastasis, 2-4 weeks before the surgical intervention for hepatectomy.
      We expose 17 cases to which we performed such a combined therapy, between 1995
      1997. We had to postoperative death after major hepatectomies. The other patients
      are survived by our clinics.

PMID- 9656604
TI  - Normative data for a brief neuropsychological battery administered to English-
      and Spanish-speaking community-dwelling elders.
AB  - The use of neuropsychological tests in non-English-speaking populations and among
      those with less education has been limited because most tests have been
      standardized for English-speaking populations with relatively high levels of
      education. In effort to establish norms, a battery of neuropsychological tests
      was administered, in either English or Spanish, to 995 normal elders with a wide
      range of educational attainment, residing in the community of Washington Heights
      Inwood in northern Manhattan. Results indicate that age, education, and language
      all influence test performance and should be considered when evaluating
      neuropsychological measures.

PMID- 9656605
TI  - Verbal learning and memory in alcohol abusers and polysubstance abusers with
      concurrent alcohol abuse.
AB  - To define the combined effects of drug and alcohol abuse on verbal learning and
      memory, 70 alcoholic and 80 polysubstance abuse (PSA) individuals with concurrent
      alcohol abuse were compared on a list learning task, the California Verbal
      Learning Test (CVLT). Despite demonstrating similar learning strategies, response
      styles, and error patterns, the PSA group nontheless exhibited significantly
      greater recall deficits than the alcoholic group on the CVLT. These deficits were
      particularly evident in those who were heaviest abusers of cocaine. PSA
      participants did not, however, evidence greater recognition memory deficits. This
      pattern of greater deficits on recall than on recognition memory, as well as poor
      consolidation, is consistent with the initiation-retrieval difficulties of
      patient groups with subcortical dysfunction. It is concluded that the combined
      use of alcohol and drugs, cocaine in particular, may compound memory difficulties
      beyond what is typically observed in alcoholic individuals.

PMID- 9656606
TI  - Information processing and antiretroviral therapy in HIV-1 infection.
AB  - Computerized reaction time (RT) tasks are sensitive measures of subclinical HIV
      related mental slowing. We previously reported that nondemented HIV-seropositive
      patients on antiretroviral therapy at the time of testing had faster choice RTs
      compared to matched untreated seropositive participants. In the present study, we
      evaluated the performance of 163 nondemented HIV-seropositive participants on a
      reaction time version of the Stroop task as a function of antiretroviral status.
      Persons on antiretroviral therapy at the time of testing had significantly faster
      reaction times than untreated individuals, although treated asymptomatic
      participants showed significantly less Stroop interference than treated
      symptomatic participants. These effects could not be attributed to differences in
      demographic variables, disease status, substance abuse, or psychological
      distress. These data indicate that central information processing is faster for
      patients treated with antiretroviral compounds compared to untreated patients,
      and suggest that reaction time tasks may have significant potential utility in
      clinical trials of neuroprotective compounds.

PMID- 9656607
TI  - Long-lived picture priming in normal elderly persons and demented patients.
AB  - Normal elderly control participants showed short-term (10-min delay) and long
      term (12 months delay) priming on the Gollin Figures Test. Nearly all patients
      with Alzheimer's disease or vascular dementia showed short-term priming, but the
      magnitude of their priming was less than that of controls. Significant long-term
      priming was not observed for the dementia groups. Differences between controls
      and dementia patients on the short-term priming test may depend upon structural
      perceptual processes that are intact in dementia patients and controls and
      explicit memory functions available only to controls. The same model could
      account for differences between normal elderly and dementia patients on the long
      term priming test, but several other explanations are also plausible.

PMID- 9656608
TI  - Comparative effects of schizophrenia and temporal lobe epilepsy on memory.
AB  - The goal of this study was to further characterize episodic memory functioning in
      schizophrenia. This study compared verbal and visual learning and memory
      performance in (1) patients with schizophrenia (N = 35), (2) patients with
      temporal lobe epilepsy (TLE; N = 30), and (3) normal controls (N = 25). Results
      indicated significant memory impairments in patients with schizophrenia and TLE.
      "Savings" score measures of memory decay showed that the loss of information in
      schizophrenia and TLE was approximately equal, and quantitatively mild compared
      to that found in most neurologic groups with memory disorders. The severe
      difficulty shown by the schizophrenia group on a task of incidental recall
      suggested that the absence of instructional set added to a vulnerability to
      memory deficit. In contrast, relatively mildly impaired performance on paired
      associate learning suggested that patients with schizophrenia benefited from
      retrieval cues, multiple trials, and short (nonsupraspan) informational loads.
      Because patients with schizophrenia consisted of a relatively nonchronic sample
      with a mean IQ of 99.7, their memory disorder could not be attributed to
      schizophrenic dementia, nor was it accounted for by other potential confounds.
      Patients with schizophrenia, even those relatively early in the course of
      illness, have a mild episodic memory disorder.

PMID- 9656609
TI  - A comparison of clustering solutions for cognitive heterogeneity in
      schizophrenia.
AB  - A cluster analytic solution based upon a battery of tests consisting of the
      Halstead Category and Tactual Performance Tests, the Trail Making Test, and the
      Wisconsin Card Sorting Test was compared with a solution based on the subtests of
      the Wechsler intelligence scales, utilizing a sample of 221 schizophrenic
      patients. Both analyses permitted four-cluster solutions, and we found a weak but
      significant degree of association between solutions. Examination of external
      validity of the two solutions revealed stronger associations with clinical
      variables for the Wechsler-scale-based solution. The major conclusions were that
      the existence of cognitive heterogeneity in schizophrenia exists across a broad
      range of abilities, and appears to reflect a combination of continuity of ability
      level and existence of possible subtypes requiring further neuropsychological and
      neurobiological verification.

PMID- 9656610
TI  - Neuropsychological comparisons of Spanish-speaking participants from the U.S.
      Mexico border region versus Spain.
AB  - Two samples of participants from the U.S.-Mexico Borderland (N = 185) versus
      Spain (N = 205) were compared on 16 Spanish-language neuropsychological measures.
      In most measures the two samples obtained similar results. There were some
      significant main effects of place of birth and some significant interactions
      between education and place of birth. Differences between the samples diminished
      with increasing levels of education. Within the Borderland sample, percent of
      life span spent in the U.S. and bilingual status were correlated with performance
      in some tests. Increased percent of life span spent in the U.S. was negatively
      correlated with performance on a Spanish word-generation task, and positively
      correlated with performance on the Wisconsin Card Sorting Test. Bilingual
      Borderland participants performed significantly better than monolingual speakers
      in learning a list of words. We suggest that the most likely causes for the
      observed interaction effects are documented regional differences in early SES
      related nutrition, medical care, quality of educational experiences, and general
      socioeconomic conditions.

PMID- 9656611
TI  - Characteristics of impaired awareness after traumatic brain injury.
AB  - Impaired awareness of the effects of brain injury is a commonly observed and
      poorly understood finding in traumatic brain injury survivors. Nonetheless,
      impaired awareness has been identified as a major factor in determining outcome
      for traumatic brain injury survivors. Review of previous studies of impaired
      awareness in this patient population revealed a number of preliminary findings
      regarding the nature of this phenomenon. The present paper presents the results
      of 2 new studies with a total of 111 traumatic brain injury patients conducted to
      bring further clarity to this area. Findings confirmed and extended many results
      of previous investigations. Specific findings included patient overestimation of
      functioning as compared to family member ratings, patient report of greater
      physical than nonphysical impairment, greater patient-family agreement on
      specific ratings of patient functioning than on general ratings, greater
      agreement of family and clinician ratings of patient functioning with each other
      than with patient self-ratings, and partial disagreement of different methods of
      measuring impaired awareness.

PMID- 9656612
TI  - Primary progressive semantic aphasia: a case study.
AB  - A longitudinal case study of a patient with a progressive loss of meaning of
      objects with preserved phonology and syntax is presented. Repeated measures of
      language, praxis, visual cognition, and semantic processing were carried out. The
      patient still has preserved conversational speech, social skills, and orientation
      in her 8th year of her illness, but shows severe anomia and comprehension deficit
      in all modalities of stimulus presentation. In addition to standardized tests of
      language, cognition, and memory, specific experiments of categorization,
      modalities of word access, item consistency, category specificity, and definition
      of words were carried out. Results indicate a frequency dependent loss of meaning
      that was consistent in all modalities and throughout all object categories.
      However, the relative preservation of visual categorization of all categories
      tested and the language based categorization of animals suggested some
      fractionation of semantic memory. Relative preservation of autobiographical and
      personal memories versus semantic memory was a striking observation. Evidence for
      selective impairment of central semantic processing was obtained from experiments
      indicating item consistency of loss and the lack of semantic cuing. Neuroimaging
      evidence of left temporal lobe atrophy and the classical picture is compatible
      with similar cases published under the term semantic dementia or "transcortical
      sensory aphasia with visual agnosia" and suggest the diagnosis of Pick's disease.

PMID- 9656613
TI  - External cueing systems in the rehabilitation of executive impairments of action.
AB  - The use of a mnemonic cueing system (NeuroPage) and a paper and pencil checklist
      in the rehabilitation of executive problems in a 50-year-old woman are described.
      Following a CVA 7 years earlier, the patient, despite intact general intellectual
      and memory functioning, had specific executive impairments of attention,
      planning, realizing intended actions, and also exhibited behavioral routines
      similar in form to obsessive-compulsive rituals. In a series of ABAB single-case
      experimental designs, the efficacy of 2 external cueing systems in prompting
      appropriately timed action is demonstrated. It is argued that the combination of
      external control and increased sustained attention to action were critical to the
      success of NeuroPage with this patient. Furthermore it is hypothesized that the
      checklist was effective in facilitating the patient's ability to foresee and
      recognize the consequences of her actions, which in turn had an impact on the
      probability of her changing those same actions.

PMID- 9656614
TI  - Addressing a continuum of recovery after acquired brain injury.

PMID- 9656615
TI  - "A golden decade" for kidney medicine. Gene therapy is expected to result in a
      new break through.

PMID- 9656616
TI  - [A currently developed method of measurement. A discovery of specific nerve
      fibers explains the way of itching through the body].

PMID- 9656617
TI  - [Positive results after open thoracic surgery among the elderly].

PMID- 9656618
TI  - [Confusing guidelines for psychotherapy].

PMID- 9656619
TI  - [We appeal for the change of the circumcision rite].

PMID- 9656620
TI  - [Double messages to persons with problems due to amalgam and computer screens].

PMID- 9656621
TI  - [More stringent directives are necessary when it comes to non-prescription
      drugs].

PMID- 9656622
TI  - [Klinefelter syndrome affects mostly boys. An underdiagnosed chromosome
      abnormality].
AB  - Although Klinefelter's syndrome is the most common sex chromosome anomaly,
      affecting one in 5-800 boys, our knowledge of the syndrome is still poor. This is
      reflected in the paucity of published literature as compared, for example, with
      the vastly greater number of publications on Turner's syndrome with its lower
      incidence of 1/2,500 girls. Klinefelter's syndrome is manifestly underdiagnosed.
      Existing knowledge mainly derives from cases characterised by prominent
      symptomatology. Early diagnosis is important if additional support and resources
      are to be made available to the patient and his family. Testosterone replacement
      therapy should be initiated as soon as clinical and laboratory evidence becomes
      available. In selected cases, testosterone treatment can be started already
      during adolescence. At present, there is no established treatment for the
      infertility which almost always accompanies the condition.

PMID- 9656623
TI  - [Ticks--a medical topic of current interest which sticks].

PMID- 9656624
TI  - [Good results of concentration on the care of heart failure in Malmo. Emergency
      admissions to hospital were reduced by 24 per cent].

PMID- 9656625
TI  - [National psychiatric guidelines compiled].

PMID- 9656626
TI  - [A forgotten fraudulent bean--a case of favism. Fava bean may cause life
      threatening hemolysis in predisposed persons].

PMID- 9656627
TI  - [Reduced drug costs with the reference cost system].

PMID- 9656628
TI  - [Three cases of nerve injury in connection with orthopedic laparoscopic surgery].

PMID- 9656629
TI  - [A conflict between physicians and nurses about the drug lists. Please, do not
      disturb--the drug documentation is going on].

PMID- 9656630
TI  - [Better and cheaper care in heart failure. Efficient care programs save
      resources].

PMID- 9656631
TI  - [A new series: coronary vessels. Good strategy saves more patients with acute
      coronary syndrome].

PMID- 9656632
TI  - [Unbiased neutral handling is wanted for the inspection of hospital departments].

PMID- 9656633
TI  - [Occupational environment of interns may be improved with the help of special
      ombudsmen].

PMID- 9656634
TI  - [Insinuating negative quotation on veterinary medicine].

PMID- 9656635
TI  - [On the blessings of acupuncture].

PMID- 9656636
TI  - [Emergency coronary care--successful, but unequaly distributed].
AB  - The need of acute coronary care is increasing because of an increase in the
      incidence of severe angina pectoris, and despite a reduction in that of acute
      myocardial infarction. Patients with acute myocardial infarction are
      characterised by continuously increasing age, lower mortality, and shorter
      hospitalisation. The improvement in acute care is related to increased use of
      expensive drugs, new diagnostic methods, and an increasing coronary
      revascularisation rate. However, there is still inequality in the utilisation of
      cardiac care, and in order to further enhance its quality and equality of
      utilisation, there is an emphatic need of common registries.

PMID- 9656637
TI  - [The man behind Paget's syndrome. He gave name to diseases of the skeleton,
      breast and vulva].

PMID- 9656638
TI  - [Pharmacological pain analysis as diagnostic and therapeutic help].

PMID- 9656639
TI  - [Heart failure is expensive! Correct drug utilization can reduce the number of of
      expensive days in hospital].

PMID- 9656640
TI  - [New drugs against insulin resistance].
AB  - Insulin resistance is an important mechanism in the development of the insulin
      resistance syndrome and type 2 diabetes. Although treatment has hitherto been
      confined to metformin or non-pharmacological measures, efforts are now being made
      to discover new drugs active against insulin resistance, so-called insulin
      sensitisers, for instance among the thiazolidinedione group. These are beginning
      to be tested in larger clinical trials where they have manifested effects not
      only on glucose metabolism but also on other cardiovascular risk factors such as
      hyperlipidaemia, defective fibrinolysis, and hypertension. However, adverse
      reactions to one of these drugs, troglitazone, include severe hepatic effects in
      certain cases. Accordingly, registration of the product has been stopped for use
      in Europe, but not in the USA and Japan. It is likely to take some time before
      thiazolidinediones will be introduced for clinical use in this country, though
      research and development continue.

PMID- 9656641
TI  - [Postoperative laryngospasm may induce pulmonary edema. An unusual or overlooked
      complication?].
AB  - Young and healthy patients in whom laryngospasm secondary to postoperative
      extubation is encountered run a risk of developing pulmonary edema. The mechanism
      behind the edema is thought to be a strongly negative intrathoracic pressure
      generated by the patient's forced inspiration against a closed glottis. A net
      flow of fluid occurs to the interstitial space and further to the alveoli.
      Unusually the pulmonary edema can be noticed within a few minutes after relief of
      the obstruction, but occasionally it is delayed for several hours. The condition
      is potentially life-threatening, but usually responds favourably to positive
      pressure ventilation and diuretics. In anaesthesia and intensive care, it is
      important to be aware of the complication in order to be ready for adequate
      therapy when needed. We present three cases from the Central Hospital in Vaxjo,
      where pulmonary edema occurred directly following postoperative extubation.

PMID- 9656642
TI  - [Surgery and/or talk. Dialogue is as important as diagnosis-based measures].

PMID- 9656643
TI  - [Tooth injuries in connection with intubation anesthesia: severity of the disease
      and dental status].

PMID- 9656644
TI  - [The king of Bavaria, creator of the fabulous castle, killed his psychiatrist].

PMID- 9656645
TI  - Estimation of variance components based on diallel model.
AB  - The problem of estimation of variance components based on diallel model for
      unbalanced data has been addressed. The least squares approach to quadratic
      estimation has been adopted in obtaining the explicit solutions for the design
      and genetic components of variance.

PMID- 9656646
TI  - Some perspectives on modeling leukemia.
AB  - A diffusion model of leukemia is presented. The space-occupying effects of
      leukemic cells during leukemic expansion is investigated. The analyses and
      simulations of the model suggest that acute leukemia is a state in which
      positions inhabited by colonies of normal cells are invaded by emerging colonies
      of abnormal cells. Normal cells are then driven to a state of extinction as
      leukemic cells evolve toward high and dominant steady state levels.

PMID- 9656647
TI  - Analysis of a dengue disease transmission model.
AB  - A model for the transmission of dengue fever in a constant human population and
      variable vector population is discussed. A complete global analysis is given,
      which uses the results of the theory of competitive systems and stability of
      periodic orbits, to establish the global stability of the endemic equilibrium.
      The control measures of the vector population are discussed in terms of the
      threshold condition, which governs the existence and stability of the endemic
      equilibrium.

PMID- 9656648
TI  - The deterministic limit of infectious disease models with dynamic partners.
AB  - This paper analyzes the large population dynamics of an infectious disease model
      with contacts that occur during partnerships. The model allows for concurrent
      partnerships following a very broad class of dynamic laws. Previous work, with a
      stochastic version of the model, computed the reproductive number, the initial
      growth rate, and the final size. In the present paper, the deterministic system
      that is the limit for large populations is constructed. The construction is
      unusual in requiring two different scaling factors. Next, the approximation used
      by Watts and May for a related model is compared with the exact solution. This
      approximation is most accurate at the beginning of the epidemic and when
      partnerships are short. Lastly, the model is generalized to allow dependencies
      among partnerships. This generalization permits proportional mixing with an
      arbitrary distribution on the number of partners.

PMID- 9656649
TI  - Existence and uniqueness of endemic states for the age-structured S-I-R epidemic
      model.
AB  - The existence and uniqueness of positive steady states for the age structured S-I
      R epidemic model with intercohort transmission is considered. Threshold results
      for the existence of endemic states are established for most cases. Uniqueness is
      shown in each case. Threshold used are explicitly computable in terms of
      demographic and epidemiological parameters of the model.

PMID- 9656650
TI  - Utilizing data systems to develop and monitor occupational health programs in a
      large Canadian hospital.
AB  - With rapid change in health care requiring greater emphasis on productivity and
      quality management, occupational health hazards in hospitals have been receiving
      increasing recognition, now not only focusing on controlling infection, but also
      on chemical, physical, mechanical as well as psychosocial hazards. Reducing
      costly time loss from musculoskeletal injuries is a particular imperative. The
      Department of Occupational and Environmental Medicine at Winnipeg's Health
      Sciences Centre, developed databases to help priorize, monitor and improve
      occupational health programs for its 6,000 employees. Risk assessment/risk
      management models were adopted to identify hazards, quantify risks and priorize
      intervention. Using the databases permitted the targeting of groups requiring
      immunization, resulting in increased coverage. New safety products were
      introduced and found to be cost-beneficial. A return-to-work post-injury program
      was particularly cost-beneficial. Over the five years following the
      implementation of occupational health programs, workers' compensation assessment
      reductions resulted in savings of more than half-a-million dollars annually. The
      databases were invaluable in affecting these changes.

PMID- 9656651
TI  - HRA model for hypercholesterolemia based on a longitudinal health database.
AB  - To evaluate the risk factors for hypercholesterolemia, we examined 4,371 subjects
      (3,207 males and 1,164 females) who received medical checkups more than twice at
      an AMHTS in Tokyo during the period from 1976 through 1991; and whose serum total
      cholesterol was under 250 mg/dl. The mean follow-up duration was 6.6 years. A
      self-registering questionnaire was administered at the time of the health
      checkup. The endpoint of this study was the onset of hypercholesterolemia when
      the level of serum total cholesterol was 250 mg/dl and over. We compared two
      prognosis groups (normal and hypercholesterol) in terms of age, examination
      findings and lifestyle. After assessing each variable, we employed Cox's
      proportional hazards model analysis to determine the factors related to the
      occurrence of hypercholesterolemia. According to proportional hazards model
      analysis, total cholesterol, triglyceride and smoking at the beginning, and
      hypertension during the observation period were selected in males; and total
      cholesterol at the beginning and age were selected in females to determine the
      factors related to the occurrence of hypercholesterolemia.

PMID- 9656652
TI  - A health condition survey of Japanese people in the prime of life, based on
      national MHTS and human dry dock statistics.
AB  - A health condition survey was made of Japanese persons in the prime of life
      regarding six abnormalities (obesity, impaired glucose tolerance, hypertension,
      hypercholesterolemia, hypertriglyceridemia, liver dysfunction) occurring with
      high frequency. It was demonstrated that impaired liver function and elevation in
      blood cholesterol are the main causes of health deterioration in persons in the
      prime of life. The survey results suggest that the deterioration of their health
      is associated with their lifestyle.

PMID- 9656653
TI  - Elimination of inter-institutional discrepancies in health check-up results:
      standardization of diagnostic decision level and uniformity of examination data.
AB  - In Japan, more people are taking AMHTS and the number of medical institutions
      where it is provided is also increasing. AMHTS is expected to continue to expand
      in scope and importance from now on. People do not necessarily take AMHTS at the
      same medical institutions year after year. For AMHTS to be truly useful from the
      viewpoint of preventive medicine and be able to continue its development, it is
      imperative that the level of diagnosis be standardized and the compatibility of
      examination data be established among different institutions. The Japan Society
      of MHTS is conducting pilot studies of reversed quality control (RQC) as part of
      its activities with the aim of clearly understanding inter-institution gaps
      regarding AMHTS and to establish uniformity in examination data.

PMID- 9656654
TI  - Health risk appraisal in the UK--some preliminary results.
AB  - Information about a subject's lifestyle, personal past history and family history
      of disease is obtained from a 70-item questionnaire. This information is then
      used to compute the subject's risk of dying from certain diseases, relative to
      the average risk for a person of the same age and sex.

PMID- 9656655
TI  - Dietary balance chart for an on-line computerized graphical support system in
      MHTS.
AB  - Dietary habits are believed to play an important role in the etiology of adult
      disease. For this reason, it is necessary to include effective dietary guidance
      in multiphasic health testing and services (MHTS) programmes for primary disease
      prevention. We have developed such a programme of simple dietary advice, using a
      computer system for the MHTS. Examinees' dietary habits are checked using optical
      character record (OCR) questionnaire forms, and the results are displayed on the
      screen of a colour display terminal. They are required to prepare a menu of their
      usual daily dietary intake in terms of quantity and type of food. Thus the data
      collected relate to the nutritional composition of the examinee's usual diet.
      Nutritional requirements of the Japanese according to sex, height, and level of
      physical activity, in accordance with criteria set by the Japanese Ministry of
      Health and Welfare, are fed into the computer in advance. For each examinee,
      these criteria and the results of the assessment of the diet are displayed
      together on the screen in the form of colour graphs for comparison.

PMID- 9656656
TI  - Prevalence and conditions of urinary incontinence among the elderly.
AB  - In Japan, elderly disorders and diseases have markedly increased in recent years,
      because of rapid aging and an increasing number of older persons. The situation
      is creating serious social and community problems. These disorders, particularly
      dysuria and urinary incontinence (UI), disturb the quality of life (QOL) in
      latelife. Few reports on UI have been published, but precise investigation into
      the community level remains to be made. Our presentation is the development,
      implementation and evaluation of elderly UI in Kumamoto Prefecture. This study
      includes 2,304 people (male: 856, female: 1,448), over 65 years of age, living in
      two different communities; one is an urban (K) and the other is a typical rural
      area (S). The rate of UI was in homebound elderly persons, male: 4.7%, female:
      11.3%, and in nursing home residents, male: 16.2%, female: 23.2%. The condition
      of UI was: almost Urinary Urgency in male (61.5%), and Stress Incontinence (such
      as, caused by coughing, sneezing, and exercise) in female (46.3%). The influence
      of UI on the activity of daily life was investigated. Most of the male cases were
      giving concerns for family and community. In contrast, females hesitated to
      participate in group excursions and outdoor exercise, and had a tendency to live
      alone or indoors. However, most persons (81.5%) with UI did not visit a
      physician. From this investigation, we conclude that a community health care
      program and public support system are essential for proper understanding and
      solution of the elderly UI problem.

PMID- 9656657
TI  - Total quality in information systems management: issues for the health care
      industry.
AB  - Faced with rising costs, growing demand and declining funding, hospitals and
      others must either cut services or improve the efficiency and effectiveness of
      what they do. Neither solution can be implemented without adequate relevant
      information. Without understanding which services are providing the most value to
      its customers, sensible cutbacks will be difficult to make. Improving efficiency
      requires a knowledge of where there are inefficiencies, and improving
      effectiveness requires an understanding of what the outcomes of health care are.
      The solution, as many have documented, is to create, as a first step, a database
      containing detailed health care patient data. In this paper, we present
      continuous improvement techniques as a requirement for the design and development
      of this much needed database.

PMID- 9656658
TI  - The SNOMED model: a knowledge source for the controlled terminology of the
      computerized patient record.
AB  - This article will present a description of the semi-implicit semantic properties
      of the Systematized Nomenclature of Human and Veterinary Medicine, also called
      SNOMED International. It will focus on the formalism of SNOMED and its
      computational properties using the disease definition as an example. Additional
      information will be provided in order to convert semi-implicit links found
      between SNOMED concepts into explicit computational semantic links.

PMID- 9656659
TI  - Informatics in the service of health, a look to the future.
AB  - The paper attempts a balanced look at the directions of health informatics
      required in the future. In a high level review of impediments to health and
      health care a number of issues are identified that may be amenable to improvement
      by contributions from health informatics. Attention is drawn to the improvement
      of the collection and dissemination of knowledge in addition to the analysis of
      morbid conditions as a focus for health informatics. On this basis a review of
      the current state of health information systems is undertaken. The importance of
      adaptable user interfaces for end users and systems personnel, privacy and
      confidentiality protection, and linkage among clinical support systems and
      knowledge repositories is stressed. These improvements hinge on advancements in
      medical concept representation. Canadian contributions to these developments,
      particularly the instigation of Evidence Based Medicine (EBM) are briefly
      reviewed.

PMID- 9656660
TI  - Tailoring communications for primary care settings.
AB  - In more and more medical settings, physicians have less and less time to be
      effective communicators. To be effective, they need accurate, current information
      about their patients. Tailored health communications can facilitate positive
      patient-provider communications and foster behavioral changes conducive to
      health. Tailored communications (TCs) are produced for an individual based on
      information about that person. The focus of this report is on tailored print
      communications (TPCs). TPCs also enhance the process of evaluation, because they
      require a database and the collection of patient-specific information. We present
      a Tailoring Model for Primary Care that describes the steps involved in creating
      TPCs. We also provide examples from three ongoing studies in which TPCs are being
      used in order to illustrate the kinds of variables used for tailoring the
      products that are developed and how evaluation is conducted. TPCs offer
      opportunities to expand the reach of health professionals and to give
      personalized, individualized massages in an era of shrinking professional contact
      time.

PMID- 9656661
TI  - Informatics methodologies for evaluation research in the practice setting.
AB  - A continuing challenge in health informatics and health evaluation is to enable
      access to the practice of health care so that the determinants of successful care
      and good health outcomes can be measured, evaluated and analysed. Furthermore the
      results of the analysis should be available to the health care practitioner or to
      the patient as might be appropriate, so that he or she can use this information
      for continual improvement of practice and optimisation of outcomes. In this paper
      we review two experiences, one in primary care, the FAMUS project, and the other
      in hospital care, the Autocontrol project. Each project demonstrates an
      informatics approach for evaluation research in the clinical setting and
      indicates ways in which useful information can be obtained which with appropriate
      feed-back and education can be used towards the achievement of better health.
      Emphasis is given to data collection methods compatible with practice and to high
      quality information feedback, particularly in the team context, to enable the
      formulation of strategies for practice improvement.

PMID- 9656662
TI  - Periodical multiphasic screening and lung cancer prevention.
AB  - The purpose of this work is to evaluate the utilization of information gathered
      by multiphasic screening with respect to lung cancer detection and smoking
      cessation techniques. A cohort (follow-up) study is reported in which cancer
      incidence and factors affecting its occurrence are evaluated in a group of about
      20,000 presumably healthy adults along a period of approximately 10 years
      following comprehensive multiphasic health examinations. Lung cancer occurrence
      is primarily related to smoking. The risk is higher in smokers and is dose
      dependent; OR = 0.21, (CI = 0.08, .53) in never smokers, OR = 1.53 (CI = 0.8,
      3.2) in past and current moderate smokers, OR = 4.92 (CI = 2.18, 11.11) in
      current heavy smokers. Moreover, smokers with compromised pulmonary function
      (FEVI/FVC < 75%) are at an even higher risk of developing lung cancer OR = 4.22
      (CI = 2.2, 8.2) for past and current moderate smokers; and OR = 10.7 (CI-2.5,
      38.6) in current heavy smokers. Information gathered in periodical multiphasic
      health examinations could be utilized by health professionals to encourage
      smoking cessation and smoking prevention in the appropriate screenees. Various
      elements of the multiphasic test results could contribute to such prevention
      efforts. While every smoker should receive appropriate evaluation and
      consultation regarding nicotine dependence, smokers with reduced pulmonary
      function represent an extra high risk group to which special attention should be
      given.

PMID- 9656663
TI  - Obstruction of valid race/ethnicity data acquisition by current data collection
      instruments.
AB  - Methods of collecting race/ethnicity data affect the validity of conclusions
      based on them as do other factors such as lack of consensus and inadequate
      definitions for terminology; and misclassification or miscounting of patients.
      Current data collection instruments do not identify mixed heritage. We propose
      improving data measurement and collection by including a quantified
      multiracial/multiethnic heritage category for persons of mixed heritage; a don't
      know category; and a refuse to reveal category. The resulting problems affect all
      uses of racial and ethnic data, including health care provision, research, and
      health planning. More precise race/ethnicity categories should be encouraged by
      such means as a 16-category checklist (with instructions to check all which
      apply) currently in development. The Methods section of all clinical,
      epidemiologic, and pharmacologic reports should include descriptions of racial
      measurement and reasons for including or excluding clearly defined populations.

PMID- 9656664
TI  - Evaluation of complication rates after coronary artery bypass surgery using
      administrative data.
AB  - Our objectives were (1) to determine if studying hospital complication rates
      after coronary artery bypass graft (CABG) surgery provides information not
      available when only mortality is studied, and (2) to reexplore the utility of ICD
      9-CM administrative data for CABG outcomes assessment. Using data from
      Massachusetts, we identified CABG cohorts from 1990 and 1992 to respectively
      develop and validate multivariate risk adjustment models predicting in-hospital
      mortality and complications. The resulting models had good discrimination and
      calibration. In 1992, adjusted hospital complication rates ranged widely from
      13.0% to 57.6%, while mortality rates ranged from 1.4% to 6.1%. Hospitals with
      high complication rates tended to have high mortality (r = 0.74, p = 0.006), but
      2 of the 12 hospitals studied ranked quite differently when judged by
      complications rather than mortality. We conclude that (1) complications after
      CABG occur frequently and may provide information about hospital quality beyond
      that obtained from hospital mortality rates, and that (2) administrative data
      continue to be a promising resource for outcomes research.

PMID- 9656665
TI  - Interactive video assists in clinical decision making.
AB  - The Hawaii Quality and Cost Consortium began a project in 1993 to implement and
      evaluate interactive videodisk programs to assist in clinical decision-making for
      breast cancer. Communication problems between physicians and patients,
      limitations of available outcomes data and varying preferences of individual
      patients can result in treatment outcomes that are less than satisfactory. Shared
      Decision-making Programs (SDPs) were developed by the Foundation for Informed
      Medical Decision Making (FIMDM) in Hanover, New Hampshire, to assist in the
      treatment decision-making process. Utilizing interactive videodisks, the programs
      provide patients with clear, unbiased information about available treatment
      options. With this information, patients can become more active participants in
      making treatment decisions. The SDPs for breast cancer were implemented at two
      sites in Hawaii. Evaluation data from 103 patients overwhelmingly indicate that
      patients find the programs clear, balanced and very good or excellent in terms of
      the amount of information presented and overall rating.

PMID- 9656666
TI  - [Regulation and pathophysiology of airway secretion].
AB  - Although excessive production of sputum is one of the characteristic features of
      acute and chronic respiratory infections, bronchiectasis, diffuse
      panbronchiolitis, chronic bronchitis and asthma, pathophysiological mechanisms
      underlying airway hypersecretion remain uncertain. The increase in intraluminal
      mucus may lead to impairment of airway mucociliary clearance and deterioration of
      bronchial obstruction. Airway surface fluid is composed of mucus glycoprotein
      released from submucosal glands and goblet cells and water from airway epithelial
      cells, and the secretory function can be regulated by autonomic nervous system
      and a variety of chemical mediators. It is thus important to select
      mucoregulating drugs after understanding the mechanisms of hypersecretion and
      impaired mucociliary transport under individual conditions.

PMID- 9656667
TI  - [A guide for the timing of peripheral blood stem cell harvest in patients with
      lung cancer].
AB  - Harvest of peripheral blood stem cells (PBSC) was performed 57 times in 17 lung
      cancer patients after standard-dose chemotherapy (cisplatin, etoposide)
      supplemented with granulocyte-colony stimulating factor (G-CSF). In every case,
      more than 1.5 x 10(6)/kg CD 34+ cells were collected by 2-5 apheresis.
      Statistical significance was noted between peripheral leukocyte counts (WBC) and
      collected CD 34+ cell counts (p = 0.0298), between peripheral platelet counts and
      collected CD 34+ cell counts (p = 0.0009), and between the peripheral immature
      granulocyte ratio and collected CD 34+ cell counts (p < 0.0001). Because of the
      remarkable relationship between collected CD 34+ cell counts and peripheral WBC
      counts, peripheral platelet counts and the peripheral immature granulocyte ratio,
      these parameters were useful for determining the correct timing of PBSC harvest.

PMID- 9656669
TI  - [Clinicopathological study of six cases of primary pulmonary lymphoma diagnosed
      by gene rearrangement analysis].
AB  - We report six cases of primary pulmonary lymphoma in which a gene-rearranged band
      was shown by Southern blot analysis of transbronchial or surgical biopsy
      specimens. The cases were 3 mens and 4 women with an average age of 59.6, who had
      abnormal pulmonary shadows on chest X-ray. Two cases had Sjogren's syndrome and
      one case had monoclonal gammopathy (IgM-lambda type). Histopathologic and
      immunologic examination revealed diffuse infiltration of small lymphocytes (B
      cell type) in all cases, and histological features of lymphoepithelial lesion or
      lympho-cytic interstitial pneumonia (LIP) in three cases. CT revealed an ill
      defined margin, air-space consolidation, and air-bronchogram in all cases. A CT
      angiogram sign was apparent in 2 cases. In all cases, Southern blot analysis of
      the tissue obtained from transbronchial or surgical biopsy revealed a gene re
      arranged band, supporting the diagnosis of primary pulmonary lymphoma. We infer
      that an ill-defined margin, air-bronchogram and air space consolidation on CT
      were associated with the histopathological features of primary pulmonary
      lymphoma.

PMID- 9656668
TI  - [Effect of adenosine and its analogues on microvascular leakage in the rat
      trachea].
AB  - We examined the effects of adenosine and its analogues on vascular permeability
      in rat trachea using Evans blue dye as a marker for plasma leakage. Inhalation of
      N6-2-(4-aminophenyl) ethyladenosine (APNEA), a specific A 3 receptor agonist,
      increased microvascular leakage in a dose-dependent manner, but adenosine, [R]-N6
      (1-Methyl-2-phenylethyl) adenosine (R-PIA), aspecific A 1 receptor agonist, and
      5'-(N-ethyl-carboxamide) adenosine (NECA), a specific A 2 receptor agonist, had
      no effect. Inhalation of capsaicin increased vascular permeability in a dose
      dependent manner. Pretreatment with NECA (10-1000 nmol/kg, i.v.) but not
      adenosine (100 nmol/kg i.v.), R-PIA (100 nmol/kg, i.v.) or APNEA (100 nmol/kg,
      i.v.) inhibited microvascular leakage produced by capsaicin aerosol (3 x 10(-5)
      M) in a dose-dependent manner. However, NECA (10-100 nmol/kg, i.v.) failed to
      inhibit substance P aerosol (10(-4) M)-induced extravasation of the dye. These
      findings suggest that stimulation of adenosine A 3 receptors produces airway
      vascular permeability, and that A 2 receptors inhibit neurogenic plasma
      extravasation, presumably by inhibiting the release of tachykinins from sensory
      nerves.

PMID- 9656670
TI  - [Determinant factors of pulmonary function and respiratory muscle strength on
      exertional dyspnea in patients with chronic obstructive pulmonary disease
      (COPD)].
AB  - The effects of pulmonary function and respiratory muscle strength on exertional
      dyspnea in patients with chronic obstructive pulmonary disease (COPD) have not
      been fully elucidated. We examined the relationships between pulmonary function,
      static respiratory pressure, and dyspneic sensation during exercise in 48
      patients with COPD. Dyspneic sensation during exercise was quantitated by a Borg
      scale slope (BSS, BS/VO2) and the threshold load of dyspnea (TLD). BSS was
      negatively correlated with VC, FEV1, V 25, RV/TLC (%). DLCO and PImax, whereas
      TLD was positively correlated with VC, FEV1, V 25, FRC and RV/TLC. Linear
      regression analysis revealed that FEV 1 and FRC were independent predictors for
      TLD, and that RV/TLC (%) was an independent predictor for BSS. These results
      suggest that an increase of air trapping as indicated by RV/TLC may be a major
      factor contributing to both decreased TLD and increased BSS, resulting in an
      increased sensation of dyspnea during exercise in patients with COPD.

PMID- 9656671
TI  - [Metastasis of small cell lung cancer to the parotid gland as the initial
      clinical manifestation, followed by metastases to the pituitary gland and lumber
      spinal cord].
AB  - The patient was a 48-year-old woman. In January 1995, she noted swelling in the
      left parotid gland, and saw an otorhinolaryngologist. Needle biopsy showed small
      cell carcinoma, and she was subsequently admitted to our hospital. Chest
      radiography revealed a tumor shadow in the hilus of the right lung. Bronchial
      biopsy revealed small cell carcinoma of the lung (T 4 N 3 M 1, stage IV).
      Chemotherapy, with a CDDP-VP-16 regimen, achieved no response. She later
      developed bitemporal hemianopsia and abducens nerve palsy. Brain MRI revealed
      metastasis in the pituitary gland. Chemotherapy and radiotherapy were efficacious
      for only a few months. She also developed pain and numbness in the left leg,
      attributable to intramedullary metastasis (L 1/2, L 4/5) shown on MRI. It is
      extremely rare for a metastasis to the parotid gland to be the initial clinical
      manifestation of a small cell lung cancer which later develops widespread
      metastases to the pituitary gland and lumbar spinal cord.

PMID- 9656672
TI  - [Two cases of severe adult varicella pneumonia].
AB  - Varicella pneumonia is the most common complication of adult varicella. Symptoms
      may be severe and the mortality rate high in patients who are immunodeficient or
      pregnant. Symptoms may be mild and progression more favorable in adults
      previously in good health. We report two cases of varicella infection complicated
      by severe pulmonary involvement in adult patients who were previously healthy.
      Case 1 was a 36-year-old male who 6 days after developing varicella was
      clinically observed to have dyspnea and hemopytsis. He died of acute respiratory
      failure on the following day. Case 2 was a 28-year-old male whose respiratory
      symptoms started the third day after developing varicella. These symptoms were
      relieved by treatment with acyclovir and gammaglobulin. Careful observation is
      and an early treatment of varicella should be undertaken not only for patients
      with suppressed cellular immunity, but also for healthy adults, to prevent severe
      complications.

PMID- 9656673
TI  - [A case of Wegener's granulomatosis which showed early spontaneous remission].
AB  - An 80-year-old woman presented at our hospital on October 1995 with fever,
      hemoptysis and a cavitary shadow on chest X-ray. Blood examination revealed an
      accelerated erythrocyte sedimentation ratio and elevated CRP. Pulmonary
      cryptococcosis was suspected, but serological tests and bronchoscopic examination
      for cryptococcus were both negative. There was also no evidence of the
      tuberculosis or malignancy. She was treated with the antibiotic cefpirome sulfate
      intravenously for thirteen days. Her chest X-ray and abnormal blood test findings
      became almost completely normal following the i.v. antibiotic treatment. In
      February 1996 (2 months after her first admission), she had severe right cheek
      pain, and Coldwell Luc's operation was performed after right maxillary sinusitis
      was diagnosed. A high fever (39 degrees C) continued after surgery, and multiple
      cavitary shadows were seen on chest X-ray. Blood examination revealed an
      accelerated ESR, elevated CRP and slightly elevated c-ANCA. She was treated with
      i.v. infusion of antibiotics and antifungal drug's, but did not improve.
      Wegener's granulomatosis was diagnosed after transcutaneous lung biopsy and
      histopathological examination of the maxillary sinus. Dramatic improvement was
      seen following treatment with oral cyclophosphamide and prednisolone. Whether her
      first remission was due to antibiotic treatment or spontaneous is an interesting
      question.

PMID- 9656675
TI  - [Non-small cell lung cancer metastatic to the stomach and the jejunum causing
      intussusception: a case report].
AB  - We report a case of lung cancer metastatic to the stomach and the jejunum.
      Adenocarcinoma of the lingula (T 4 N 2 M 0) was diagnosed in a 45-year-old man,
      who then underwent chemoradiotherapy. Bowel obstruction later developed due to
      jejunal metastasis. Another metastasis was detected in the stomach. Laparotomy
      revealed jejuno-jejuno-jejunal intussusception caused by the two lesions. The
      jejunal and gastric lesions were identified as metastatic large cell carcinoma
      arising from the lung. One month postoperatively, the patient died due to
      disease. The literature has demonstrated that large cell carcinoma of the lung
      tends to metastasizes. However, the complex bowel invagination and gastric
      metastasis seen in our case are rare.

PMID- 9656674
TI  - [A case of pleuritis caused by strongyloides in a carrier of T-cell lymphoma
      virus type I (HTLV-I)].
AB  - A 73-year-old woman was admitted to our hospital complaining of dyspnea, fever
      and general edema. Chest roentgenogram showed bilateral pleural effusion and
      cardiomegaly. Cardiovascular examination demonstrated atrial tachycardia and left
      ventricle dysfunction, suggesting congestive heart failure. She was sero-positive
      for human T-cell lymphoma virus I (HTLV-I). The dyspnea and general edema
      improved after therapy for heart failure. Because the pleural effusion persisted
      after therapy, thoracentesis was performed. The pleural effusion was an exudate,
      and Strongyloides sterocoralis was detected by microscopy. Two courses of
      thiabendazole (1,500 mg/day, 3 days) were given orally. After this therapy, the
      pleural effusion improved markedly. This case suggests that Strongyloides
      stercoralis may be a causative agent of pleuritis in HTLV-I endemic areas.

PMID- 9656676
TI  - [A case of idiopathic interstitial pneumonia with marked increase of CA19-9 in
      serum and BALF].
AB  - A 84-year-old man was admitted with dyspnea. Chest X-ray and CT showed
      honeycombing in the dorso-basal segments of the lung bilaterally. Idiopathic
      interstitial pneumonia (IIP: chronic, typical type) was diagnosed in accordance
      with the clinical criteria proposed by the Japanese Ministry of Health and
      Welfare. An extensive examination revealed no malignancy. However, the CA 19-9
      level in bronchoalveolar lavage fluid (BALF) was very high (5,700 U/ml). An
      immunohistochemical test of lung tissue obtained by transbronchial lung biopsy
      was positive for CA 19-9 in bronchiolar epithelial and goblet cells. This case
      suggests that CA 19-9 is occasionally produced on a large scale in the lung of
      patients with IIP.

PMID- 9656677
TI  - [Legionella pneumonia caused by aspiration of hot spring water after sarin
      exposure].
AB  - A 72-year-old man was exposed to the sarin gas attack in a Tokyo subway on March
      20 th, 1995. After exposure, he noticed eye discomfort, chest tightness, headache
      and weakness of the lower limbs and oropharyngeal muscles. Despite these
      symptoms, he visited a hot spring on the same day with his family. On March 25
      th, his muscle weakness progressed, and a low grade fever appeared. His muscle
      weakness disappeared 8 days after exposure to sarin, but respiratory failure
      rapidly developed, necessitating artificial ventilation within four day after
      hospitalization on March 28th. Chemotherapy with erythromycin,
      imipenem/cilastatin, and steroid pulse therapy was begu. PCR and culture of
      sputum collected by bronchofiberscopy were positive for Legionella pneumophila,
      serogroup I. His respiratory state improved, but subsequent infection with
      Pseudomonous aeruginosa. Enterobacter cloacae, and Candida tropicalis/glabrata
      caused his death 71 days after admission. Oropharyngeal muscle weakness caused by
      sarin-mediated cholinesterase inhibition was strongly suspected as the cause of
      hot spring water aspiration. Transbronchial lung biopsy revealed organizing
      pneumonia with fibrosis. Bronchoscopic findings included redness, edema and
      fragility of all visible areas of the airway, which was thought to be due to
      bronchitis caused by Legionellosis.

PMID- 9656678
TI  - [Pulmonary emphysematous changes associated with Pneumocystis carinii pneumonia
      in an AIDS patient].
AB  - A 60-year-old man was admitted to our hospital complaining of non-productive
      cough. He had worked in Africa and received a blood transfusion after a traffic
      accident in 1985. On admission, the patient had remarkable hypoxemia and a
      decreased CD4+ lymphocyte count. A serological test for human immuno-deficiency
      virus (HIV)-1 was positive. His chest radiographs showed diffuse reticular and
      linear opacities, and broncoalveolar lavage findings established a diagnosis of
      Pneumocystis carinii pneumonia (PCP). A high-resolution CT of the chest revealed
      peripheral infiltrates and low attenuation areas (LAA) consistent with severe
      emphysematous alterations. We administered high-dose methylprednisolone and
      trimethoprim-sulphamethoxazole (TMP-SMX). Because of marked eosinophilia, TMP-SMX
      was discontinued, and the patient was given inhaled pentamidine isothiocyanate.
      Although there was a striking clinical improvement, the emphysema-like lesion on
      chest CT remained unaltered. LAA on CT had been modest in 1994, but had markedly
      enlarged during the three years thereafter, leading us to speculate that most of
      the LAA lesions recognized on admission might have developed in association with
      PCP. Pulmonary function tests showed an obstructive ventilatory defect and
      impaired diffusing capacity. Although PCP classically presents with diffuse
      ground-glass or fine granular opacities, thin-walled cavities or other atypical
      findings have recently been reported, especially in AIDS patients. There have
      been several reports about emphysema-like lesions associated with PCP. It was
      suggested that these lesions might be due to lung parenchyma destruction induced
      by HIV itself or increased elastase release from HIV-infected macrophages. This
      is the first report of PCP with pulmonary emphysematous lesions in Japan.

PMID- 9656679
TI  - [Invasive thymoma successfully treated with high-dose chemotherapy followed by
      peripheral blood stem cell transplantation(PBSCT)].
AB  - A 42-year-old man was admitted with chest pain. A large mass in the anterior
      mediastinum was seen on a chest X-ray film and confirmed by CT. Surgery was
      performed, but the tumor was nonresectable because it had invaded the aorta and
      pulmonary artery, and had disseminated to the pericardium. Invasive thymoma
      (stage IVa) was diagnosed He initially received two courses of ADOC (50 mg/m2 of
      cisplatin, 40 mg/m2 of doxorubicin, 0.6 mg/m2 of vincristine, and 700 mg/m2 of
      cyclophosphamide) at 3-week intervals. Four weeks after the 2 causes of ADOC, he
      was given 300 mg/m2 of etoposide for five days followed by G-CSF subcutaneously
      for peripheral blood stem cell collection. After the two courses of ADOC, he
      received high-dose ICE (1.5 g/m2 of ifosfamide for four days, 400 mg/m2 of
      carboplatin for three days, and 200 mg/m2 of etoposide for five days) followed by
      peripheral blood stem cell transplantation (PBSCT). He was given G-CSF after
      PBSCT, with subsequent rapid neutrophil and platelet recovery. The tumor
      diminished remarkably in size and complete remission was confirmed pathologically
      at subsequent thoractomy. Postoperatively, 50 Gy of irradiation was given. These
      observations suggest that high-dose ICE followed by PBSCT in combination with an
      ADOC regimen, surgery, and radiotherapy is highly effective and well tolerated in
      patients with advanced nonresectable thymoma.

PMID- 9656680
TI  - [A case of secondary invasive pulmonary aspergillosis originating from an
      aspergilloma, successfully treated with itraconazole].
AB  - A 65-year-old man was admitted to our division with of productive cough and
      hemosputum. Chest radiographs and chest CT on admission showed old inflammatory
      shadows in both upper lung fields and a fungus ball in the left upper lung field.
      Despite antibiotic treatment, the patient's sputum volume increased and
      Aspergillus niger was repeatedly cultured from his sputum. Chest radiographs
      showed deterioration around the intracavitary fungus ball and a test for serum
      aspergillus antigen was positive. Secondary invasive pulmonary aspergillosis
      originating from aspergilloma was diagnosed based on his clinical symptoms,
      radiographic features and laboratory data. Administration of fluconazole failed
      to improve his clinical course and amphotericin B was discontinued because of
      hypokalemia. Oral administration of itraconazole was a successful treatment.

PMID- 9656681
TI  - [Cytokines produced by cells in bronchoalveolar lavage fluid from a patient with
      primary pulmonary cryptococcosis].
AB  - Cytokines in the culture supernatant of concanavalin A-stimulated
      macrophages/lymphocytes isolated from bronchoalveolar lavage (BAL) fluid in a 29
      year-old patient with primary pulmonary cryptococcosis were evaluated to study
      the immune reaction against Cryptococcus neoformans in the lung. Before
      fungicidal therapy, levels of interferon-gamma and interleukin-10 were markedly
      elevated, and declined after therapy. There were no changes in interleukin-2 or
      interleukin-4 throughout the clinical course. This result suggests that IFN-gamma
      and IL-10 may be involved in the immune reaction against pulmonary
      cryptococcosis.

PMID- 9656682
TI  - [A case of sea water and sand aspiration during near drowning].
AB  - A 46-year-old man who had been pulled under water by a tidal wave when an
      earthquake occurred on July 12, 1993 was carried to our hospital the next day. He
      soon needed endotracheal intubation and mechanical ventilation because he
      expectorated sputa with sand and because arterial bloodgas analysis revealed
      severe hypoxemia. Chest X-ray on admission showed diffuse small nodules and areas
      of consolidation. Chest CT obtained on July 16 showed centrilobular small nodules
      bilaterally and alveolar opacities in the peribronchial region. After therapy
      with antibiotics and frequent bronchial lavages, sputum with sand disappeared on
      the 14 th hospital day and chest X-ray film and laboratory data showed marked
      improvement. He was discharged on October 1. A chest CT scan obtained on February
      17, 1994 showed improvement of the small nodules. The areas of consolidation had
      also improved, but remained as linear and nodular opacities, which were
      considered to be organized lesions. There are few reports concerning radiographic
      findings particularly CT findings, after aspiration of sea water and sand during
      near drowning.

PMID- 9656683
TI  - [Nodular bronchioloalveolar carcinoma with multiple small air spaces caused by
      bronchiolectasis].
AB  - A 67-year-old man was admitted to our hospital with a faint abnormal shadow in
      the right S2 on January 1995. Chest CT showed a faint abnormal shadow about 3 cm
      in diameter with multiple small air spaces. He was admitted again 18 months later
      for surgical treatment because the shadow on chest X-ray had grown. Right upper
      lobectomy was performed in June 1996 and pathohistological examination revealed
      bronchioloalveolar carcinoma. Tumor cells along the walls of the alveolus were
      recognized only in the periphery of the lesion. The center of the lesion was
      fibrotic and multiple small air spaces ranging from 0.5 mm to 10 mm in diameter
      were present. One cause of these air spaces was considered to be the "check
      valve" mechanism, but the majority of the air spaces were derived from ectatic
      bronchioli. These results suggested that bronchiolectasis had developed with
      central fibrosis only in the tumor. Central fibrosis in this case had played a
      significant role in determining the radiographic appearance of the lesion.

PMID- 9656684
TI  - [Thresholding algorithms in automated static perimeter].

PMID- 9656685
TI  - [Evaluation of the Swedish Interactive Thresholding Algorithm, a new thresholding
      algorithm, of the Humphrey field analyzer in normal subjects].
AB  - The Swedish Interactive Thresholding Algorithm (SITA) is a new thresholding
      algorithm that aims to obtain the same quality of visual fields in a shorter
      examination time than with the conventional up-and-down method. We investigated
      the correlation between thresholds measured with the SITA algorithm and those
      with the conventional up-and-down method in 47 eyes of 47 normal subjects. In
      each test point, thresholds with the SITA accurate and with the SITA fast showed
      significant correlation with those of the conventional method (r = 0.693, p <
      0.0001 and r = 0.689, p < 0.0001, respectively). The mean deviation (MD) in the
      conventional method and the difference between MD values of the conventional
      method and SITA accurate and SITA fast were significantly correlated (r = -0.442,
      p < 0.006 and r = -0.509, p < 0.00092, respectively). The examination times of
      the SITA accurate and SITA fast were 48% and 27% of the conventional method.
      Although the new thresholding algorithm enables us to perform perimetric
      examination with relatively high accuracy, further investigations should be
      conducted before we apply it to glaucoma cases.

PMID- 9656686
TI  - [Influences of trabeculectomy combined with the use of mitomycin C on corneal
      endothelial cells].
AB  - We used a specular microscope to evaluate the corneal endothelial cells in 119
      eyes before and 2 to 3 weeks after trabeculectomy with topical mitomycin C. The
      endothelial cell density per square millimeter averaged 2,569 +/- 487 (mean +/-
      standard deviation) before surgery and 2,444 +/- 536 after surgery, showing a
      decrease of 4.98%. The hexagonality decreased by 1.7%, the coefficient of
      variation increased by 1.9, and the average cell area increased by 6.82%. There
      were no statistical differences as a whole in these values. Decrease in
      hexagonality was more frequent in eyes with prior intraocular or glaucoma
      surgery. Eyes treated by laser trabeculoplasty showed a decrease in endothelial
      cell density, an increase in coefficient of variation and an increase in
      hexagonality. Eyes with postoperative flat anterior chamber showed significant
      changes in each parameter. The findings show that trabeculectomy with topical
      mitomycin C does not significantly affect the corneal endothelial cells at 2 to 3
      weeks after surgery.

PMID- 9656687
TI  - [Choroidal venous dilatation in serous retinal detachment].
AB  - We studied the correlation between choroidal venous dilatation, intrachoroidal
      leakage of dye, and subretinal leakage from the choroid in patients with serous
      retinal detachment unaccompanied by choroidal neovascularization. We reviewed 13
      eyes with anamnesis of serous retinal detachment, 23 eyes without anamnesis, and
      one eye of unknown status of a total of 37 eyes. Regarding the relationship
      between subretinal dye leakage from the choroid in fluorescein angiography (FAG)
      and choroidal venous dilatation in indocyanine green angiography (ICG), the point
      of subretinal leakage (31 points) was on and/or in the neighborhood of the site
      of choroidal venous dilatation in 87.1% of the 27 eyes, except for eyes of
      unknown site of leakage in FAG. The point of subretinal leakage was within and/or
      in the neighborhood of the intrachoroidal leakage of dye in ICG in 92% of the
      eyes. In serous retinal detachment without choroidal neovascular membranes,
      serous retinal detachment may be caused by breakdown of the outer retinal barrier
      due to choroidal venous congestion and intrachoroidal diffusion.

PMID- 9656688
TI  - [Use of a scanning laser tomograph to evaluate the optic disc of the normal
      eyes].
AB  - We evaluated the optic disc in 77 eyes of 77 normal volunteers using a scanning
      laser tomograph (Heidelberg Retina Tomograph: HRT, version 1.11). Particular
      attention was paid to age, refractive error, and disc size. The topographic
      parameters included: cup area, C/D area ratio, rim area, cup volume, rim volume,
      mean cup depth, maximum cup depth, cup shape measure, height variation contour,
      mean RNFL thickness, and RNFL cross section area. There was a significant decline
      in mean RNFL thickness and RNFL cross section area with increase in age (p <
      0.05). The mean and maximum cup depths were significantly deeper in myopic eyes
      (p < 0.05). Large discs had large values of cup area, C/D area ratio, rim area,
      cup volume, mean cup depth, cup shape measure (p < 0.01), and maximum cup depth
      (p < 0.05). Large discs had small values of mean RNFL thickness and RNFL cross
      section area. Rim volume was independent of age, refractive error, or disc area.

PMID- 9656689
TI  - [Relationship between age and thickness of the retinal nerve fiber layer in
      normal subjects].
AB  - We measured the thickness of retinal never fiber layer (RNFLT) in the
      peripapillary area in 120 eyes of 60 normal subjects. We used a scanning laser
      polarimeter, or Never Fiver Analyzer (NFA) by Laser Diagnostic Technologies, USA.
      Measurements were made along the peripapillary ring with the diameter of 1.75
      disc diameter (DD) and another one 0.8 mm away from the disc margin. The RNFLT
      was not significantly correlated with age along The two rings. The RNFLT ratio of
      total/nasal area significantly decreased with increase in age. There was an
      increase in the difference of RNFLT between both eyes with increase in age in
      spite of considerable interindividual variations. The RNFLT values along both
      rings thus showed age-related changes in normal subjects.

PMID- 9656690
TI  - [Surgical indications and results of primary pars plana vitrectomy for
      rhegmatogenous retinal detachments].
AB  - To evaluate the efficasy of primary vitrectomy for uncomplicated rhegmatogenous
      retinal detachment associated with posterior hyaloid separation, a series of 63
      eyes were reviewed retrospectively. The criteria for vitrectomy included not only
      eyes with posterior retinal breaks but also those with multiple peripheral
      retinal breaks. The reattachment rate was 92.1% (58 eyes) after the initial
      surgery, and finally this increased to 100%. Of the 46 eyes with macular
      detachment, good visual rehabilitation, i.e., visual acuity improved by 5 or more
      lines, was obtained in 71.8% (33 eyes) one month postoperatively. There was no
      statistically significant difference in the reattachment rate whether an
      encircling procedure was also done or not. In eyes with lens opacity, cataract
      surgery was also done and intraocular lenses were implanted uneventfully in all
      but one myopic case. No serious complications such as proliferative
      vitreoretinopathy were found throughout the follow-up period except for the high
      incidence (53.8%) of cataractous progression. The results indicate that
      vitrectomy, removing the peripheral vitreo-retinal traction directly, is an
      effective procedure for primary rhegmatogenous retinal detachment. Vitrectomy
      combined with cataract surgery is also proposed as a valuable strategy in
      selected cases to maintain visual rehabilitation.

PMID- 9656691
TI  - [A case of corneal abscess with impetigo contagiosa].
AB  - Impetigo contagiosa often occurs on the face of children. Although the eyelid and
      conjunctiva are frequently affected, no corneal involvement has been reported in
      Japan. We encountered a case of impetigo contagiosa with corneal abscess. The
      patient, an 8-year-old boy, complained of pain and presented with corneal abscess
      and iritis in the right eye as well as eruptions in the inferior eyelid and
      around the anterior nostrils. He was diagnosed as having impetigo contagiosa with
      corneal abscess. Because the corneal abscess and eruptions occurred at the same
      time and coagulase-positive Staphylococcus with identical drug sensitivity was
      isolated from both lesions, we considered the corneal lesion as a part of the
      impetigo contagiosa. When impetigo contagiosa occurs around the eye, especially
      on the eyelids, a careful examination of the anterior segment of the eye is
      needed.

PMID- 9656692
TI  - [Indocyanine green video angiographic findings of frosted branch angitis in a
      child].
AB  - A 10-year-old boy presented with typical fundus findings of frosted branch
      angitis in both eyes. Fluorescein angiography showed late-phase hyperfluorescence
      in some active areas of vascular lesions. Indo-cyanine green (ICG) angiography
      showed similar but less extensive hyperfluorescence along the frosted vessels and
      in the disc. ICG angiography also showed filling delay in the choriocapillaris.
      These findings suggest that frosted branch angitis is a manifestation of
      inflammation in the retina and the choroid. Laboratory studies showed increase in
      the toxoplasma titer at 1:10,240 and in the serum levels of alpha 1 and alpha 2
      globulin. Frosted branch angitis in this case seemed to be the consequence of
      local allergic reaction, or immune complex deposition, presumably due to
      toxoplasma infections.

PMID- 9656693
TI  - [Medial collateral ligament of the knee and its surroundings: MRI findings of
      normal and abnormal structures].
AB  - Normal and abnormal structures of the medial corner of the knee were evaluated
      with coronal and axial MR images. MRI revealed 35 medial collateral ligament
      (MCL) tears and 61 medial meniscus (MM) tears in 200 consecutive examinations.
      Just under the MCL, little or no fluid retention was identified between the
      superficial and deep layers of the MCL or between the MM and MCL in normal knees
      and in cases of MM tears. At the anterior aspect of the MCL, the deep layer
      merges with the capsule of the suprapatellar bursa, potentially leaving space for
      fluid retention. Fluid collection posterior to the MCL was demonstrated in a few
      cases. Fluid retention with edematous swelling just under the MCL was noted in
      the cases of MCL tears. MM-MCL distances in the cases of normal structure, MM
      tears and MCL tears were 2.1 mm, 2.7 mm and 4.7 mm, respectively. The deep layer
      of the MCL, which was enhanced by the presence of joint fluid, was identified in
      71% of cases.

PMID- 9656694
TI  - [Clinical study of transcatheter arterial embolization for pulmonary
      arteriovenous fistula].
AB  - PURPOSE: To evaluate the efficacy of transcatheter arterial embolization for
      pulmonary arteriovenous fistula (PAVF). MATERIALS AND METHODS: Eight patients
      with 14 PAVFs were treated by TAE for feeding arteries. In 5 of 8 cases,
      detachable balloons were used, and, in 3 of 8 cases, metalic coils were used for
      embolization of the feeding arterial branch. Detachable balloons or a series of
      metalic coils were placed at the feeding artery proximal to the fistula. The
      diameter of detachable balloons was twice the diameter of the feeding arterial
      branch. The diameter of metalic coils was 1 mm larger than the diameter of the
      feeding artery. RESULTS: No complications were apparent in our cases. All PAVFs
      were completely occuluded by the embolization of a feeding branch. One month
      after the procedures, the arterial oxygen pressure increased to normal values in
      all cases and clinical symptoms disappeared. On postcontrast CT, the fistulas
      treated by the embolization of a feeding arterial branch were not enhanced.
      CONCLUSION: The embolization of a feeding branch provided a radical cure for
      PAVFs.

PMID- 9656695
TI  - [Endoscopic findings of esophagitis in concurrent chemo-radiotherapy for lung
      cancer].
AB  - We performed esophageal endoscopy with concurrent chemo-radiotherapy for lung
      cancer in 19 patients. Endoscopical examination proved that seven patients
      (36.8%) had esophageal erosion or coating (grade 2), four patients (21.1%) had
      ulcer or bleeding (grade 3) confined to the radiation field, and only one patient
      (5.3%) had severe symptoms (WHO grade 3). There was a discrepancy between
      patients' symptoms and endoscopical findings. Endoscopically proven esophagitis,
      that is, erosion or coating (grade 2), and ulcer or bleeding (grade 3), was more
      frequent in the daily low-dose chemotherapy group (5/5) than in the full dose
      chemotherapy group (5/14) (p < 0.05). One patient with grade 3 endoscopial damage
      showed less recovery in spite of three months medication. In concurrent
      radiochemotherapy in which the radiation field includes the esophagus, careful
      attention should be given to radiation esophagitis, which may be underestimated
      when assessed on the basis of subjective symptoms alone. Therefore, endoscopy is
      recommended even if patients have few complaints, and once the esophageal ulcer
      is proven (grade 3), it should be closely followed up using endoscopy.

PMID- 9656696
TI  - [Evaluation of 99mTc-DTPA-HSA abdominal imaging of protein-losing
      gastroenteropathy].
AB  - Abdominal images were obtained after the intravenous injection of 99mTc-HSA-D in
      8 patients with protein-losing gastroenteropathy (PLG). Six neck images and 7
      abdominal images were obtained in 11 patients with ischemic heart disease as a
      control study. We evaluated all the images with respect to visualization, initial
      appearance time, and movement of abnormal radioactivity. In 7 of 8 patients with
      PLG, abnormal radioactivity in the intestine appeared from 10 min to 4 hours
      after injection, and moved 6 hours after injection. In 6 of 7 abdominal images of
      control cases, slight activity was observed in the alimentary tract 6 hours or 24
      hours after injection. The thyroid was not visualized in any of the 6 cases. In
      conclusion, if radioactivity in the alimentary tract was first observed 6 hours
      or later after injection, the diagnosis of PLG may be difficult by this method
      alone. It still may be necessary to perform the alpha 1-antitrypsin test for the
      correct diagnosis of PLG.

PMID- 9656697
TI  - [Radiobiological considerations for stereotactic irradiation].
AB  - Stereotactic radiosurgery (SRS: stereotactic irradiation [STI] delivered in a
      single high dose) was initially developed by Leksell for non-malignant brain
      lesions, but there has been increasing interest in using it to treat small
      primary brain tumors or metastases. In more recent years, stereotactic
      radiotherapy (SRT: fractionated STI) has been developed, but radiobiological
      factors have not been sufficiently evaluated in relation to these techniques.
      Larson classified potential STI targets into four categories according to whether
      the target tissue is early- or late-responding and whether it is embedded within
      or only surrounded by normal tissue. We have actually calculated biologically
      effective doses for these categories to determine the indications for SRS and
      SRT, and to be able to choose suitable SRT schedules. Based on our calculations,
      theoretically SRS would be recommended for AVMs and benign tumors having distinct
      margins separating them from surrounding normal tissue and SRT would be
      recommended for low or high grade astrocytomas without clearly defined boundaries
      and metastasis. Recommended SRT schedules would be 49 Gy/7 fractions, 52 Gy/8
      fractions or 54.9 Gy/9 fractions completed within 2 weeks. However, clinically,
      these indications and SRT schedules should be modified according to the many
      other factors involved in individual cases, such as tumor size, presence of tumor
      necrosis, the patient's general condition, prognosis, and so on.

PMID- 9656698
TI  - [3D-CT cystography with perspective volume-rendering].
AB  - We evaluated the clinical utility of 3D-CT cystography using the perspective
      volume rendering technique in 5 patients with disorders of the urinary bladder
      and prostate. Unlike the conventional orthostatic volume-rendering technique, the
      capability of optional visual point settlement in the urinary bladder precluded
      cutting a subset of acquired data for luminal inspection, and permitted
      observation closer to lesions. Consequently, the technique enabled the evaluation
      of the accurate size, shape, and relation to adjoining mucosa and the region
      shaded by bulky tumor. 3D-CT cystography using the perspective volume-rendering
      technique facilitated 3-D inspection of the bladder lumen.

PMID- 9656699
TI  - [Clinical usefulness of ultrasound (US) database and reporting system].
AB  - Our US database and reporting system is a relational database designed for US
      image-management and navigation through volumes of US images, ACR code, text and
      diagnostic reports. This program, running on a network of Unix servers and
      Macintosh clients, supports jukebox 5 inch optical disks for data storage. With
      simple keywords for ACR code, we can make a cross-reference and categorize US
      images of teaching files.

PMID- 9656701
TI  - [A trial to reduce cardiac motion artifact on HR-CT images of the lung with the
      use of subsecond scan and special cine reconstruction algorithm].
AB  - We describe our trial to reduce cardiac motion artifacts on HR-CT images caused
      by cardiac pulsation by combining use of subsecond CT (scan time 0.8 s) and a
      special cine reconstruction algorithm (cine reconstruction algorithm with 180
      degree helical interpolation). Eleven to 51 HR-CT images were reconstructed with
      the special cine reconstruction algorithm at the pitch of 0.1 (0.08 s) from the
      data obtained by two to six contagious rotation scans at the same level. Images
      with the fewest cardiac motion artifacts were selected for evaluation. These
      images were compared with those reconstructed with a conventional cine
      reconstruction algorithm and step-by-step scan. In spite of its increased
      radiation exposure, technical complexity and slight degradation of spatial
      resolution, our method was useful in reducing cardiac motion artifacts on HR-CT
      images in regions adjacent to the heart.

PMID- 9656700
TI  - [Normal sternal bone marrow MRI using STIR].
AB  - The MR signal of sternal bone marrow was examined in 21 normal volunteers using a
      sagittal STIR sequence. Craniocaudal phase-encoding with a hand-made positioning
      device effectively eliminated artifacts due to cardiac pulsation. The sternal
      bone marrow signal could be classified into three patterns based on the signal
      distribution. The superior segment of the manubrium showed characteristic age
      related changes. This method provided high spatial resolution and excellent bone
      marrow imaging. Knowledge of a normal marrow signal pattern may be useful for the
      evaluation of hematological disorders.

PMID- 9656702
TI  - [Vascular endothelial cell injury in allergic vasculitis].

PMID- 9656703
TI  - [Usefulness of magnetite as an MRI contrasting agent in an experimental cerebral
      ischemic model. Evaluation of lesion detecting time].
AB  - Gd-DTPA has a T1 shortening effect that enhances the contrast in MRI and is
      widely used for the clinical evaluation of CNS diseases, though it is not
      suitable for the detection of cerebral ischemic regions during the superacute
      stage. Superparamagnetic iron oxide particles have a T2 shortening effect on
      relaxation time, reducing signal intensity on T2-weighted MRI in normal cerebral
      tissue. From this perspective we tested the feasibility of detecting ischemic
      lesions during the superacute stage using superparamagnetic iron oxide particles
      enhanced MRI. Male Sprague-Dawley rats were anesthetized using pentobarbital and
      the left middle cerebral artery was permanently occluded (lt.-PMCAO) using a
      modified version of the Koizumi method. After lt.-PMCAO, 100 mumoles Fe/kg, 1
      ml/kg magnetite, superparamagnetic iron oxide particles, (magnetite-injected
      group, n = 9) or physiological saline (vehicle-injected group, n = 9) was
      injected into the femoral vein. T2-weighted MR images were performed at
      designated time points immediately after injection of magnetite or vehicle on a
      6.34 T MR unit. Additionally, in separate animals coronal sections of the brain
      were stained with 4% 2, 3, 5 triphenyl-tetrazolium-chloride (TTC) to confirm the
      infarct region. In the magnetite-injected group, a high signal area at the region
      of lt.-MCA was visible within-20 to 30 min following lt.-PMCAO, whereas in the
      vehicle-injected group no high signal ischemic area could be confirmed until 3 h
      after lt.-PMCAO. Infarction was noticed in the TTC staining 3 h following lt.
      PMCAO. In this study magnetite injection allowed the detection of ischemia in the
      occluded MCA area on T2-weighted MRI during the superacute stage. These results
      suggest that ischemia during the superacute stage can be evaluated using
      magnetite enhanced MRI.

PMID- 9656704
TI  - [Remote effect in patients with thalamic stroke. A study using positron emission
      tomography].
AB  - The purpose of this study was to investigate the functional relation between the
      thalamus and other cortical regions in patients with thalamic stroke from the
      view of cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen
      (CMRO2) using positron emission tomography (PET). Twenty patients with thalamic
      stroke (right lesion = 8, left lesion = 12) and 7 normal controls were studied.
      Five patients were diagnosed as having thalamic infarction, and 15 (patients were
      diagnosed) as having thalamic hemorrhage by X-CT and/or MRI scan. Regional
      cerebral blood flow and cerebral metabolic rate of oxygen were measured by PET
      using C15O2 and 15O2 steady state inhalation technique. In the left thalamic
      stroke group, CMRO2 was significantly decreased in the left cingulate, superior
      frontal, superior temporal, middle temporal, medial occipital, and thalamic
      regions, compared with the normal control group. In the right thalamic stroke
      group, CMRO2 was decreased in the left cingulate, medial occipital, right
      hippocampal, thalamic, and the bilateral cerebellar regions, compared with the
      normal control group. In the left thalamic stroke group. CBF was decreased
      significantly in the left cingulate, middle temporal, hippocampal, thalamic, and
      right cerebellar regions, compared with the normal control group. In the right
      thalamic stroke group, CBF was significantly decreased in the right hippocampal,
      thalamic and left cerebellar regions compared with the normal control group.
      These results indicate that CBF and CMRO2 decrease in some distant regions from
      thalamic lesions, perhaps due to a disconnection of neuronal fiber. Especially in
      the left thalamic stroke group, CMRO2 was decreased in the ipsilateral temporal
      regions. This result suggests that there are more intimate functional fiber
      connections between the thalamus and temporal cortex in the left hemisphere than
      in the right hemisphere.

PMID- 9656705
TI  - [Assessment of regional cerebral blood flow in subcortical infarction with
      aphasia].
AB  - We assessed the regional cerebral blood flow (rCBF) in 8 patients with
      subcortical aphasia and 8 patients with subcortical infarction without aphasia
      using the N-isopropyl-P-[123I]-iodoamphetamine autoradiography (123I-IMP ARG)
      method. In this study, we evaluated vermis to left cortex ratio of CBF. In cases
      of Broca's aphasia (N = 2), CBF was lower in the posterior frontal regions
      including Broca's area, and more hypoperfused in the posterior frontal and in the
      posterior temporal regions, including Wernicke's area of total aphasia (N = 2).
      But, it was not significantly hypoperfused in those regions in the cases of
      Wernicke's (N = 2) and amnestic aphasia (N = 2). In the subcortical aphasia,
      global CBF in the left cerebral cortex was lower than that in the right cerebral
      cortex. However, in the subcortical infarction group without aphasia there was no
      difference between CBF in the left cerebral cortex and the right cerebral cortex.
      We conclude that hypoperfusion in the left cerebral cortex was greater than that
      in the right cerebral cortex and it was probably due to dysfunction of the left
      cerebral cortex when subcortical infarction occurred with aphasia. Though some
      types of aphasia were not relative to the dysfunction of the left cerebral
      cortex.

PMID- 9656706
TI  - [A biomechanical study of anterior cruciate ligaments reconstructed with patella
      tendons augmented by absorbable artificial materials. A biomechanical study in
      rabbits].
AB  - The purpose of this study was to investigate the biomechanical properties of
      anterior cruciate ligament (ACL) reconstruction using an absorbable artificial
      material in rabbits. Experimental studies were carried out on 58 New Zealand
      white rabbits. After total resection of ACL, 22 knees were reconstructed with
      patella tendons alone (non-augmented group) and 27 knees with patella tendons
      augmented by polyglactin 910 mesh (augmented group). The animals were sacrificed
      for biomechanical testing at 0, 2, 4, 6, 8, 12 and 24 weeks, respectively, after
      the operation. The stiffness of reconstructed ACL in the augmented group showed a
      mean of 26.58 +/- 5.78 N/mm at 8 weeks, and that of the non-augmented group 16.47
      +/- 11.34 N/mm. There were significant differences between the augmented and non
      augmented groups (p < 0.05). The ultimate load and energy of the reconstructed
      ACL were also significantly higher in the augmented group than in the non
      augmented group at 8 weeks. The mean elastic module was higher in the augmented
      than in the non-augmented group, but the differences were not significant. The
      mean tan delta of both groups was significantly higher than that of the normal
      ACL at 24 weeks. These results suggests that polyglactin 910 mesh induces earlier
      maturation of transplanted patella tendons biomechanically, and may be a useful
      material for ACL reconstruction.

PMID- 9656707
TI  - [A morphological study to elucidate the differences in visceral pleura in young
      and old mice].
AB  - The pleura is not only a mechanical envelope for the lung but also represents a
      crossroad for the exchange of cells and fluids. We studied ultrastructural
      differences in the visceral pleura of male mice in a young age group (aged 1 day,
      1 week (wk), 2 wks) and an old age group (10 months (mos), 16 mos, 18 mos, 28
      mos, and 30 mos), by both scanning and transmission electron microscopy. Surface
      microvilli (SMV) of mesothelial cells appeared to be sparse at day 1, then
      gradually increased in density and reached a plateau at approximately 10 mos. The
      length of the SMV changed in parallel with density which was confirmed by a
      morphometric study. After 28 mos, the SMV was partially loose, with an irregular
      and thin appearance. The morphological properties of pleural connective tissues,
      including collagen, elastin, and fibroblasts, changed in morphology with the
      changes in mesothelial cells; the elastic layer beneath mesothelial cells formed
      at 2wks and was maintained until 28 mos; collagen bundles increased in volume
      density throughout life, whereas cellular components including mesothelial cells,
      fibroblasts, and alveolar epithelial cells became atrophic with aging. From these
      observations, we concluded that although SMV do not have any known functions in
      the pleura, they change with age in a manner that likely corresponds to the
      changes in pleural connective tissue as well as structural changes in lung
      parenchyma.

PMID- 9656708
TI  - [Hypoparathyroidism in maintenance dialysis patients (Pts)--a clinical study].
AB  - With the recent development of measurement in intact PTH, increases of
      hypoparathyroidism and adynamic bone disease have been reported in patients on
      chronic maintenance dialysis. To clarify the frequency of hypoparathyroidism in
      maintenance dialysis patients, the present study investigates the relationship
      between the occurrence of hypoparathyroidism and clinical background, several
      bone metabolic markers and the bone mineral density. We divided 298 maintenance
      dialysis patients (HD 270, CAPD 28) without parathyroidectomy into 4 groups based
      on intact PTH. Group A was absolutely hypo (intact PTH < 60 pg/ml), group B was
      relatively hypo (60 < or = intact PTH < 160), group C was normal (160 < or =
      intact PTH < 300), and group D was hyperparathyroidic (300 < or = intact PTH).
      Groups A and B together accounted for 71.8% of the patients. The mean age in
      groups A and B was higher than in group D (p < 0.05), and the dialysis duration
      was shorter (p < 0.01). The concentration of 1, 25 (OH)2D was significantly
      higher in groups A and B than in group D (p < 0.01), and remarkably higher in
      group A than in group C. The level of Ca, i-P did not differ among the groups. In
      our investigation of bone metabolic markers, group D was found to have
      significantly higher Al-p, intact-BGP, and P 1 PC compared with the other 3
      groups (p < 0.01), and the concentration of intact BGP was lower in group A than
      in groups B and C (p < 0.01). The bone mineral density measured by DEXA did not
      differ among the groups. The results suggest that, due to multiple factors, the
      actual occurrence of hypoparathyroidism in maintenance dialysis patients is
      higher than the predicted occurrence.

PMID- 9656709
TI  - [An autopsy case of Hansen's disease (LLp) with numerous M. leprae].

PMID- 9656710
TI  - [Diagnosis and treatment of joint injuries for athletes].

PMID- 9656711
TI  - [Experience of intravascular malignant lymphomatosis with urinary incontinence
      and gait disturbance].

PMID- 9656712
TI  - On the role of G protein-coupled gating parameters in the human heart muscarinic
      atrial potassium channel.

PMID- 9656713
TI  - [A study of colonic mucins in two kinds of experimental colitis model in rat].
AB  - We investigated the quantitative changes in colonic mucins of rats with colitis.
      Male Wistar rats were treated with dextran sodium sulfate (DSS) or N
      ethylmaleimide (NEM) to induce colitis. Both DSS and NEM caused depletion of
      goblet cells, infiltration of inflammatory cells and erosion at the colonic
      mucosa around the anus. Though the goblet cells decreased, colonic mucins
      increased in the distal colon. These phenomena may explain the clinical features
      of human ulcerative colitis, namely the goblet cell depletion and the mucous
      stool. The increase of colonic mucins may be a compensatory function of the colon
      tissue in response to the localized decrease of mucin production.

PMID- 9656714
TI  - [Long-term clinical course and prognosis of patients with Crohn's disease].
AB  - The aim of the present study is to clarify long-term clinical course, prognosis
      and factors influencing prognosis of patients with Crohn's disease suffering for
      more than 10 years. Sixty-eight patients (47 males, 21 females) with Crohn's
      disease in whom the clinical course could observed well at our hospital for more
      than 10 years were studied. We classified these patients into three groups (good,
      fair, bad) according to their changes of IOIBD assessment score. And we compaired
      some clinical factors in these groups to clarify factors influencing prognosis.
      The results were as follows: 1) Twelve patients (18%) were in good prognosis
      group, and 24 patients (35%) in fair one, and 32 patients (47%) in bad one. 2)
      IOIBD assessment score at the time of diagnosis, site of leision, and
      radiographic findings at the time of diagnosis showed significant difference
      between bad prognosis group and the other two groups. Although there have been
      many reports that Crohn's disease is generally progressive, our results indicated
      that more than half of the patients showed favorable prognosis during the follow
      up period for more than ten years.

PMID- 9656715
TI  - [A case of cholerae O-139].

PMID- 9656717
TI  - [A case of the primary abscess of the greater omentum].

PMID- 9656716
TI  - [Five cases of colorectal cancer complicated with ulcerative colitis].

PMID- 9656718
TI  - [A case of Cronkhite-Canada syndrome with multiple adenomas and a carcinoma of
      rectum detected after improvement of polyposis due to steroid treatment--an
      analysis of expression of p53 protein in polyps].

PMID- 9656719
TI  - [A case of autoimmune hepatitis with anti-phospholipid syndrome].

PMID- 9656720
TI  - [Heptocellular carcinoma (HCC) fed from cystic artery--report of a case and
      review of the literature].

PMID- 9656721
TI  - [Genetic hemochromatosis complicated with Schonlein-Henoch purpura showing
      various gastro-intestinal disorders].

PMID- 9656722
TI  - [A case of non-icteric middle-lower common bile duct cancer with intraductal
      superficial spread to the gall bladder].

PMID- 9656723
TI  - [An autopsy case of subcutaneous nodular fat necrosis associated with chronic
      pancreatitis].

PMID- 9656724
TI  - [A case of abdominal tuberculous lymphadenitis diagnosed by percutaneous US
      guided needle biopsy].

PMID- 9656725
TI  - Refusal to eat in the elderly.
AB  - Refusal to eat by the elderly, and subsequent malnutrition, occurs in both
      institutional and community settings. Causes include physiologic changes
      associated with aging, mental disorders such as dementia and depression, and
      medical, social, and environmental factors. Treatment approaches call for
      management of these causes while considering the roles that medicine, ethics, and
      culture play in the process.

PMID- 9656726
TI  - Orexins: a newly discovered family of hypothalamic regulators of food intake.
AB  - A family of neuropeptides from the hypothalamus, named orexins, was recently
      discovered and characterized. Orexins stimulate appetite and food consumption.
      Their genes are expressed bilaterally and symmetrically in the lateral
      hypothalamus, which was earlier determined to be the "feeding center" of the
      hypothalamus. In contrast, the so-called satiety center is expressed in the
      ventromedial hypothalamus and is dominated by the leptin-regulated neuropeptide
      network.

PMID- 9656727
TI  - Interaction of chromium with insulin: a progress report.

PMID- 9656728
TI  - Fish consumption and risk of sudden cardiac death.
AB  - Studies show conflicting results regarding the protective effect of dietary fish
      and fish oil on certain types of cardiovascular disease. A recent epidemiologic
      study supports the hypothesis that moderate consumption (1-2 meals/week) of fish
      lowers the risk of sudden cardiac death in humans.

PMID- 9656729
TI  - Underreporting of energy intake, socioeconomic status, and expression of nutrient
      intake.
AB  - The relationship between socioeconomic status and nutrient intake was examined in
      a recent study. The investigators used three different expressions of nutrient
      intake in an attempt to overcome the confounding effect of underreporting on
      interpretation of dietary intake data. Biologic validation attempts were
      inconclusive as to which expression yielded the most accurate results.

PMID- 9656730
TI  - High-fat meals and endothelial function.
AB  - Two recent studies on the effects of single high-fat meals on endothelial
      function have postulated an additional mechanism by which dietary lipids can
      impact atherosclerosis. These studies found that dietary lipids decrease the
      ability of blood vessels to dilate and that this modification of endothelial
      function was protected by dietary antioxidants. Although this research presents
      an interesting hypothesis, much more research is necessary to determine the
      importance of dietary factors on vasoactivity.

PMID- 9656731
TI  - Uncoupling proteins: beyond brown adipose tissue.
AB  - Uncoupling protein, originally described in the inner mitochondrial membrane of
      brown adipose tissue, permits the oxidation of fuels without the generation of
      adenosine triphosphate (ATP). Closely related proteins have now been found in
      many other tissues and shown to be regulated by thyroid hormones and dietary
      factors. These uncoupling proteins may play a significant role in energy
      expenditure, with implications for the development of human obesity.

PMID- 9656732
TI  - "The German standpoint concerning science and education".

PMID- 9656733
TI  - [Genesis and political background of "Sonderaktion Krakau" 6 XI 1939].
AB  - The decision to imprison Cracow's University professors on November 6, 1939 was
      made in connection with the establishment of the so-called General Government, as
      a second stage of German security police action in nazi-occupied Poland to ensure
      German rule also over Central and Southern Poland. By this way Sonderaktion
      Krakau (Special Action Cracow)--as continuation of politische Flurbereinigung
      (political cleaning up) started in German occupied Western Poland in September
      1939--was a part of a second wave of persecution directed against the Polish
      societies' social classes indicated by Nazi leaders and chiefs of German security
      police as Poland's leadership, a wave of persecution now, since the end of
      October 1939, enlarged on Central and Southern Poland. The imprisonment of the
      Cracow Professors subsequently marked the perspective, that Poland's scientific
      and academic institutions as a whole would be destroyed, so that in future no
      Polish scientists, intellectuals and university people even would have the
      possibility to do scientific work and to have subsistence from doing this kind of
      work. As a consequence, Poland's intellectuals and university-trained people as a
      social class in future would disappear indefinitely, and the people of Poland,
      deprived of intellectual leadership, would be transformed into a mass of
      dependend lower-class working people, so that the Nazi leaders mournfull future
      scenario for their rule in German occupied Central and Eastern Europe would
      become reality. By this way the imprisonment of the Cracow Professors on November
      6, 1939 was the first step to realize Nazi future plans concerning Central and
      Eastern Europe.

PMID- 9656734
TI  - [The role of world opinion in rescuing Krakow scientists involved in the
      "Sonderaktion Krakau"].
AB  - The Author, participant and victim of the "Sonderaktion Krakau", remembers
      circumstances of insidious imprisonment of Krakow professors performed on
      November 6, 1939 by SS Operation Group under command of SS-Stumbannfuhrer Bruno
      Muller. Based on archival research and relations of the participants of this
      action, he reconstructs fate of the imprisoned scientists and he analyses
      activities of political, governmental and diplomatic centers in Poland and
      particularly abroad towards liberation of the prisoners. A significant role in
      this international action was played by foreign scientific centers and
      universities as well as world press agencies. Due to this multinational
      solidarity, only 20 person out of 183 scientists imprisoned in the Sachsenhausen
      and Dachau Nazi camps lost their lives. The article is supplemented by a list of
      publications on the "Sonderaktion Krakau" written by ex-prisoners.

PMID- 9656735
TI  - ["May we not waste their deaths..." Memories of a participant in the
      "Sonderaktion Krakau"].
AB  - The Author analyses the "Sonderaktion Krakau" from historical and cultural point
      of view. Striking Polish science and national intellectual elite with an
      insidious blow, the invader reached historical experiences. In the second part
      the Author reconstructs fate of imprisoned professors and quotes many personal
      observations from the period of his stay in the Sachsenhausen and Dachau Nazi
      camps.

PMID- 9656736
TI  - [Between hope and despair].

PMID- 9656737
TI  - [Brain changes in dysraphic syndromes occurring in cases of meningomyelocele].
AB  - Neural tube defects are the most common anomalies of the CNS in the group of
      dysraphic syndromes. They occur on both encephalic and spinal levels. According
      to the title of this article we discuss some characteristic examples of
      intracranial, encephalic changes occurring in cases of meningomyeloceles. The
      special position has to be attributed to Arnold-Chiari or Chiari malformation,
      being currently under a nosological discussion. It is often restricted to its
      most typical form-Chiari II syndrome. This is characterized by the neural tube
      defect and the posterior fossa and brain-stem-cerebellum malformation with a
      displacement into the foramen magnum. The compression of the fourth ventricle and
      even secondary necrotic changes are also seen. Clinical symptoms depend on the
      topography of pathological changes. Chiari II malformation coincides in the
      majority of cases with meningomyeloceles and sometime with other spinal cord
      malformations. Meningomyeloceles coincide often with anomalies within cerebral
      hemispheres. Among them hydrocephalus deserves particular attention, occurring in
      the majority of Chiari II cases and not being rare in cases of myeloceles. The
      anomalies and/or secondary lesions of encephalic structures, particularly of the
      cortical mantle are observed, depending upon the severity of hydrocephalus and
      the onset of its development. Meningomyeloceles can also be accompanied by
      cerebral hemispheres anomalies arising in the other pathomechanism and
      developmental period than dysraphic syndromes. The midline malformations and
      anomalies of commissural system are not rare among them. In conclusion we
      emphasize that each case of CNS malformations is unique. The observed anomalies
      have to be assessed whether they form a part of a leading syndrome or occur
      together with dysraphic changes.

PMID- 9656738
TI  - [Congenital defects of the spinal part of the neural tube].
AB  - The abnormal closure of the neural tube results in defects of the nervous system
      development, which are referred to as dysraphism. Considering successive steps of
      the development of the human foetus, it can be estimated that spinal cord
      malformations arise from pathologies of early foetal development between 17th and
      28th day gestational age. This time period comprises a development of the neural
      plate and subsequently neural tube. The development is completed with a closure
      of a posterior aperture of the neural tube (caudal neuropore). Congenital
      malformations are often caused by defective closure of the caudal neuropore. The
      neural plate develops about 17th day gestational age, the cerebral vesicle
      appears about 21st day and the neural tube forms between 17th and 20th day. The
      rostral neuropore closes on the day 25th as does the caudal neuropore on the day
      28th. The embryo is 2.5 mm long at the time. Noxious factors acting during that
      period can affect normal closure of the caudal neuropore and distort the process
      of spinal cord canalization. The resultant defect is called spina bifida. This is
      the most severe form of dysraphism-rachischisis. Meninges are also affected in
      this defect. They cannot cover the neural canal and on the margins of the lesion
      are replaced by epithelium. In milder types of the defect lack of a complete bony
      framework is concealed by soft tissues, forming a sac of variable size over the
      lesion. Spina bifida can be subdivided according to the sac structure:
      meningocoele, meningocysticoele, meningomyelocoele, meningomyelocystocoele.
      Central canal pathologies constitute another form of spinal cord malformations
      presenting as hydromyelia. Abnormal closure of the neural tube may affect
      development of the vertebral column and spinal cord along their entire length or
      only at a certain portion. Malformations are seen most frequently in the lumbo
      sacral and then cervical regions.

PMID- 9656739
TI  - [Open neural tube defects in prenatal diagnosis].
AB  - The problem of open neural tube defects (ontd) is discussed in the light of
      results of prenatal tests performed in the district of Warsaw. These results seem
      to bear some epidemiological significance allowing estimation of approximate
      frequency of ontd as well as recurrence risk for the purpose of genetic
      counselling. Prenatal diagnosis of ontd is very important for individual families
      -particularly those with increased risk. However, in view of very small number of
      prenatal tests and the fact that maternal serum screening and ultrasonografic
      screening are practically not available the demographic impact of prenatal
      diagnosis in Poland on the frequency of ontd (and other genetic diseases) in
      Poland must be negligible.

PMID- 9656740
TI  - [Neural tube defects (NTD)--assessment from the perspective of 25 years of
      studies].
AB  - The present paper illustrates the authors 25-year experience in step by step
      approach to the definition of environmental and genetic background of neural tube
      defects. Based on the birth defects registry, a complete ascertainment of all
      deliveries was performed in Southern Poland during two period: 1970-1972, and
      1979-1981. The birth prevalence of neural tube defects (NTD), as well as other
      CNS malformations was determined. The empiric recurrence risk was calculated as
      3.2% +/- 1.6. Based on this figure, the relative risk (RR = 37.6 p < 0.001) and
      heritability (h2 = 74.7 +/- 6.7) were estimated. Our own modification of Morton's
      complex segregation analysis was applied. Three Mendelian (dominant, additive and
      recessive) and one multifactorial model were tested. The results did not provide
      a clear cut discrimination between different models; however the lowest 2 value
      was obtained for additive inheritance with 61% of penetrance and the frequency of
      sporadic cases equaled 55%. A search for genetic markers did not support the
      hypothesis that HLA-A,B,C loci are equivalents of T/t like locus in mice. The
      results of the study on transcobalamine levels in amniotic fluid may suggests
      that different transcobalamine metabolism reflects phenotypic expression of
      genetic susceptibility to NTD development. Current research and future
      perspectives on genetic and environmental background of NTD are also presented.

PMID- 9656741
TI  - [Congenital defects of the spinal cord and canal in neuroimaging].
AB  - Authors present the clinical classification of spinal dysraphisms and discuss all
      imaging modalities useful in the diagnosis: conventional X-rays, myelography,
      computed tomography, myelo-CT and magnetic resonance imaging. They precise the
      place of ultrasound in the prenatal and postnatal imaging of spinal dysraphisms.

PMID- 9656742
TI  - [Prevention of neural tube defects. An important health and social problem].
AB  - Central neural system congenital malformations in the form of neural tube defects
      (ntd) belong to the most common diseases leading to very serious childrens'
      disability and mortality. As it has been calculated, the number of children
      affected with ntd, delivered in Poland every year is in the range of 800-1150.
      Children with encephalocele participate in this number in app. 50%. As it has
      been found, morbidity and mortality caused by the ntd remain high and stable in
      Poland for the last 20 years. In the view of very limited possibilities of the
      treatment offered by health services, prophylactic measures remain the best
      methods for limitation of the problem. The primary prevention of ntd was
      discovered in late seventies. It has been found that folic acid added to the diet
      of women in the reproductive age reduced number of children born with ntd by 70%.
      Authors present the Programme of Primary Prevention of ntd in Poland. This
      Programme has been incorporated in the National Programme of Health for the
      Nation 1996-2005.

PMID- 9656743
TI  - [Psychologic and neuropsychologic evaluation of psychomotor development in
      children with neurological diseases].
AB  - Psychological and neuropsychological assessment of children is focused on
      behavioral disorders of various dimensions (e.g., abilities and limits of
      perceptual, expressive, cognitive and emotional functions). Additionally
      neuropsychological diagnosis attempts to explain relationship between behavioral
      and brain states. The purpose of diagnosis formulated in this way requires
      careful selection of test procedures and overall integration of different kinds
      of data. Especially, severally handicapped cases need this kind of diagnostical
      approach. Limits of valid diagnostic conclusions are determined by many factors
      that affect coherent interpretation of the test scores (e.g. the lack of a
      consistently employed neurologic model of brain development to relate to
      behavioral functions, significant impairment with coexisting sensory and motor
      deficits, the different effects of brain lesion depending on age of onset, the
      interference of maturational and experimental variables with manifestation of
      brain damage).

PMID- 9656744
TI  - [Liquidation of barriers: realization issues and legislative aspects].
AB  - Designing for the handicapped persons, aiming at the liquidation of the barriers
      is actually an essential part of the architects activity. It results from the
      fact that the handicapped persons issue became the interdisciplinary one. The
      architect, being responsible for the living space and environment creation, is to
      design the friendly environment for the handicapped persons. The space favourable
      for the handicapped is favourable for all. There are many aspects of the
      designing for the handicapped; legislative or execution issues are the examples.
      The legislative aspect is presented in this paper on the base of the contemporary
      legal rules of the Polish Republic, whereas the execution aspect is introduced
      and discussed on the basis of the two projects designed by the Design Bureau in
      Cracow and being currently in realization. These are: housing & service unit
      (Boruty-Spiechowicza Str., Cracow) and the Faculty of Philosophy complex at the
      Jesuits College (Kopernika Str., Cracow).

PMID- 9656745
TI  - [Directions and complex rehabilitation in children with neural tube defects].
AB  - A child with spina bifida is born with a potential disability. These children
      demand a long treatment and constant care of a specialist team which consists of:
      a pediatrician, pediatric surgeon, neurologist, nephrologist, specialist in
      rehabilitation and psychologist. In the treatment of the children with spina
      bifida, rehabilitating treatment is the basic and main one, which is started in
      the first days of life. The most difficult and trouble-some problem in the
      treatment of the children with spina bifida is the dysfunction of urinary bladder
      and anus sphincters which causes urine and fecal incontinence. These impairments
      often cause infections of the urinary tract, nephrolithiasis and in the later
      period, renal failure. The most vital factor influencing the effect of
      rehabilitation in children with spina bifida, the one which causes a real
      handicap, is the dysfunction of urinary bladder and anus sphincters, and not
      paresis or paralysis of the extremities.

PMID- 9656746
TI  - [Lower extremity deformities as an obstacle in rehabilitation of meningomyelocele
      patients--pathogenesis and principles of treatment].
AB  - The fate of 89 patients with meningomyelocele operated at the Institute of
      Orthopedics and Rehabilitation in Poznan between 1970 and 1989 due to paretic
      deformities of lower extremities has been traced by the authors. Deformities
      prevented nursing, standing or ambulating; their type and results of treatment
      have been related to the level of neurosegmental lesion. Modified Sharrard's
      classification served to group the patients. The level of lesion established
      during lower extremities muscles testing has been verified after neurological
      examination supplemented with electrophysiological tests: sensory response within
      L3-S2 dermatomes, afferent conduction velocity of the peroneal nerve and selected
      muscles of lower extremity electromyogram. Deformities due to inadequate nursing
      (hip and knee contractures and equinus foot) were the main obstacle in the
      rehabilitation in patients with spinal Th12-L2 lesion. In patients with L3-L5
      lesion hip contractures were accompanied by dislocation or subluxation of the hip
      due to muscular imbalance. Knee contracture was less frequent in this group and
      foot deformities were diverse. Surgical correction of paretic deformity of the
      hip was the last stage of management designed to promote rehabilitation,
      following previous foot and knee surgery. In patients with Th12-L2 lesion
      recurrence of contractures made standing and walking impossible. In patients with
      L3-L5 neurosegmental lesion surgery for paretic dislocation or subluxation of the
      hip inclusive of open reduction, varus-derotation osteotomy of the proximal
      femur, transiliac osteotomy and iliopsoas transfer to the greater trochanter
      according to Mustard resulted in stable hip. Seventy percent of patients with L3
      L4 lesion and all patients with L5 lesion profited from hip surgery with reduced
      orthotic use and effective gait.

PMID- 9656747
TI  - [Psychological consequences of neurologic motor impairment from a developmental
      perspective].
AB  - Human development is a process that continues throughout an individuals life. Any
      change of structure of function, not only of a progressive type, is a
      developmental change. Developmental defects of the neural tube, such an various
      form of myelomeningocele, which manifest themselves during the early stages of
      the intrauterine life, have an impact on the individuals further development. Its
      intensity depends on the extend of the defect itself, the feasibility of its
      correction (usually by surgical means) and a number of external, environmental
      factors which have an indirect influence on a child's development. The
      psychological consequences of such defects take the form of various disturbances
      in the development of cognitive processes: mainly the perception of the outside
      world and the formation of the cognitive structures involved in self-image
      formation. At every stage of his and her development, an individual of with a
      neural-tube defects is subject to many forms of social influence. These may
      either stimulate or hamper development. It is possible that mental development
      deficiencies observed in some individuals at a later stage result not so much
      from the defect itself as from the lack of appropriate social stimuli. The
      specific problems of children and adolescents (aged 13 to 17) with sacro-lumbar
      myelomeningocele have been discussed on the basic of a pilot study conducted at
      the hospital in Radziszow in the years 1996-1998.

PMID- 9656749
TI  - [Neurosurgical treatment of spinal dysraphism in children].
AB  - A tethered cord syndrome includes in its meaning all types of dysraphism in
      children. The syndrome is described in regard to its etiology, pathophysiology
      and clinical outcome. Next, the most prevalent types of dysraphism in children
      are presented. A surgical approach in myelocele--the most frequent defect--is
      discussed in detail. Reasons for taking a difficult decision not to operate are
      considered. The most important operative problems are also reviewed. It is
      reminded that myelocele often coexists with Arnold-Chiari malformation type II
      and hydrocephalus. Problems in selecting an appropriate surgical approach in this
      syndrome are shortly discussed. A rare syndrome of sacral agenesis, poorly
      amenable to surgical intervention, is presented. There are also some less
      frequent syndromes described, including:-sinus dermalis, potentially life
      threatening in the case of recurrent meningitis;-lipomyelocele, needing early
      identification and prophylactic surgical treatment;-diastematomyelia, in half of
      the cases requiring surgery due to a bony spur;-retethered cord syndrome, an
      iatrogenic complication of neurosurgical interventions done on the spinal cord.

PMID- 9656748
TI  - [Therapy through architecture].
AB  - The paper contains in its introductory part a short analysis of the problem of
      disability giving the proposal of the strategy for solving the problem of opening
      the built environment to the disabled people in Poland in the light of
      experiences of the countries with accessibility legislation. Promoting the idea
      that all people have only one thing in common--that they are different. To the
      present time, in the world and in Poland, the amenities provided to disabled
      persons could be regarded as being minimal in nature, satisfying basic needs. The
      necessity of disabled persons on the dependence on others, and the lack of
      independence has created a problem, whereby the disabled persons is unable to
      fully participate in social and public life, as well as partake of cultural
      amenities. Universal design is the architectural design philosophy in which the
      needs of all environment users irrespective of their physical abilities, are
      recognized in the natural way. At the end of this paper some interesting examples
      of the German designs for disabled people are presented. The main focus of the E.
      Feddersen & W. Herder Office is on the social aspect of architecture, especially
      on the designing of tenements, schools, kindergartens, hospitals and homes for
      the disabled, retarded and elderly people.

PMID- 9656750
TI  - [Urologic aspects of myelodysplasias in children].
AB  - At least 25% of the clinical problems seen in pediatric urology are the result of
      neurologic lesions that affect lower urinary tract function. The advent of clean
      intermittent catheterization and refinements in techniques of urodynamic studies
      in children dramatically changed the way this pediatric population was
      traditionally managed. Along with this change came a greater understanding of the
      pathophysiology of the many diseases that primarily affect children. The
      applicability of urodynamic testing has expanded to the point where most
      pediatric urologic centers now believe that functional assessment of the lower
      urinary tract is an essential element in the evaluation process and is as
      important as x-ray visualization in characterising and managing these abnormal
      conditions. The natural outcome of early functional investigation has been the
      advocacy of proactive or early aggressive management of children who are now
      considered at risk of urinary tract deterioration based on specific hostile
      urodynamic parameters. This paper first defines the testing process as it applies
      to children and second, conservative and surgery methods to prevent upper urinary
      tract deterioration and to correct continence.

PMID- 9656752
TI  - Early results of laparoscopic resection of colorectal cancer.
AB  - OBJECTIVE: To study the immediate and early postoperative results obtained in
      patients subjected to laparoscopic resection of colorectal cancer. PATIENTS AND
      METHOD: A prospective, observational cohort study was initiated in January 1993,
      involving 50 patients subjected to laparoscopic resection for colorectal
      adenocarcinoma (rectal amputation in 10 cases, lower rectal resection in 13,
      recto-sigmoidectomy in 18, and miscellaneous colectomies in 9 cases). Seventy
      percent of the tumors were in IUCC stages II and III. Mean follow-up was 21
      months. RESULTS: Conversion to open surgery was required in 18 cases (36%).
      Intraoperative problems were limited to a single urethral lesion, while
      postoperative complications were recorded in 11 patients (22%), and were managed
      conservatively: a urinary fistula secondary to the aforementioned urethral
      lesion; subclinical dehiscence of the anastomosis (2 cases); phlebitis (1 case);
      infection of the surgical wound (4 cases), and urinary and pulmonary infection (1
      case each). There were no differences between converted surgery (i.e.,
      conventional laparotomy) and those operations completed endoscopically (with a
      final assisted or combined minilaparotomy) in terms of the length of the surgical
      resection piece, the length of the distal margin of the specimen or the number of
      lymph nodes. Global hospital stay ranged from 9-12 days, versus 5-7 in the group
      without complications. Global survival is 78% at 42 months, with a disease-free
      interval of 53% at this time. CONCLUSIONS: Laparoscopic colorectal resection
      presents an incidence of intra- and postoperative complications characteristic of
      major surgery, with no differences in surgical specimen size with respect to
      those operations converted to laparotomy. Global survival is similar to that
      reported in the literature for open surgery.

PMID- 9656751
TI  - [Possibilities of ambulation in children with myelodysplasia].
AB  - The authors discuss the possibility of ambulation of children with
      myelodysplasia, employing different types of orthopedic devices. According to the
      personal experience of 23 myelodysplastic patients, the indications and results
      of using reciprocal gait orthoses have been described. The paper emphasizes the
      significance of interdisciplinary team in the treatment of this disease.

PMID- 9656754
TI  - Histomorphometric changes after small bowel transplantation.
AB  - AIM: Rejection results in destruction of the intestinal mucosa. This is the major
      cause of morbidity and morbility in human allografts. The aim of this study was
      to investigate histomorphometric changes in both the graft and recipient
      intestinal mucosa after experimental orthotopic small bowel transplantation.
      EXPERIMENTAL DESIGN: Using the pig model, 21 large-white pigs underwent:
      laparotomy (n = 7) (control group); orthotopic small bowel transplantation
      without immunosuppression (n = 7); and orthotopic small bowel transplantation
      with cyclosporine A (n = 7). RESULTS: 1) Significant reduction of total mucosal
      thickness (villi plus crypt) (p < 0.05) in both the graft and recipient mucosa;
      2) Attenuation of this effect by administration of cyclosporine A, which reduced
      the loss of mucosal thickness mainly at the expense of crypt hipertrophy.
      CONCLUSIONS: These findings suggest that villi and crypt length measurements may
      be a reliable method for monitoring rejection after small bowel transplantation.

PMID- 9656753
TI  - Stromal tumors of the digestive tract. Prognostic value of mitotic index.
AB  - OBJECTIVE: We analyzed the prognostic factors and evaluated the usefulness of
      mitotic index to predict the behavior of gastrointestinal stromal tumors (GIST).
      PATIENTS AND METHODS: Fifty three patients operated on for stromal tumors of the
      digestive tract were studied retrospectively. Mean follow-up was 6 years. The
      number of mitosis/10 high power fields was the definitive criterion for
      classification, regardless of their inmunohistologic differentiation. Twelve
      tumors had 0 mitoses, 34 from 1 to 9 mitoses, and 7 had > or = 10 mitoses. The
      survival rate was analyzed and the morphological characteristics and evolution
      were correlated according to mitotic index. RESULTS: The incidence of advanced
      illness was related to the number of mitoses: 29% in the group with 1 to 9
      mitoses, and 86% when there were > or = 10 mitoses. The recurrence intervals were
      44 and 8 months respectively. No tumor with 0 mitoses evolved aggressively. The
      survival rate was significantly related (p < 0.001), to the mitotic index. The
      group with 0 mitoses had a survival rate of 100% after 10 years, those with 1 to
      9 mitoses 69% and those with > or = 10 mitoses 14%. The other factors which
      influenced the prognosis (location, size, local invasion and resection) depended,
      as well, on the mitotic index. CONCLUSION: The classification of digestive tract
      stromal tumors by mitotic index is an efficient method because it distinguishes 3
      entities with different biological behavior in the long term.

PMID- 9656755
TI  - Growth hormone reduces bacterial translocation in radiation enteritis in the rat.
AB  - BACKGROUND: Radiotherapy may be considered as one of the most effective
      treatments for digestive tumours. This procedure has major side effects,
      especially in fast growing tissues like intestinal mucosa. The administration of
      drugs that reduce or avoid radiation injury of the intestinal mucosa may be
      clinically advantageous. Growth hormone is a peptide suitable for this purpose by
      modifying cell proliferation within the intestinal crypt. MATERIAL AND METHOD:
      Adult male Wistar rats were used in a model of abdominal irradiation. Each
      irradiated animal received 1200 cGy under anaesthesia and was sacrificed four and
      seven days later. The animals were treated with either saline or growth hormone
      (1 mg/kg/day) beginning immediately after the irradiation treatment. On the day
      of sacrifice, intestinal samples were taken for morphometric measurements and
      mesenteric lymph nodes for bacterial translocation. RESULTS: Mortality was of 50%
      approximately and was not affected by growth hormone treatment in irradiated
      animals. Bacterial translocation increased (p < 0.05) in irradiated animals
      whereas no significant increase was observed in rats treated with growth hormone.
      Growth hormone promotes an earlier growth of intestinal villi in irradiated
      animals (p < 0.05). CONCLUSIONS: Growth hormone promotes the morphologic
      adaptation of intestinal mucosa after abdominal irradiation, reducing bacterial
      translocation in rat.

PMID- 9656756
TI  - [Therapeutic use of albumin: a discussion on its efficacy].
AB  - The aim of our study is to discuss the current recommendations for the use of
      intravenous albumin in hypoalbuminemic patients obtained from a literature
      review. Some data available lead us to the belief that its use does not influence
      the clinical outcome of the patients, in most of the cases in which it is
      employed. Therefore its use should be limited to a certain number of clinical
      situations, in which its efficiency has been clearly shown, as in new-born in
      whom plasma expansion with small volume is necessary, in cases in which synthetic
      colloids cannot be employed, in massive paracentesis in cirrhotic patients, in
      selected cases of edema unresponsive to diuretics or other colloids in
      plasmapheresis, in kidney and liver transplant surgery.

PMID- 9656757
TI  - [Helicobacter pylori and gastric lymphoma].

PMID- 9656758
TI  - [Perforated jejunal tuberculosis in a patient with HIV-infection].
AB  - Patients with AIDS are particularly susceptible to tuberculosis infection with a
      high incidence of extrapulmonary disease and surgical complications. Authors
      describe a 38-year-old male infected with the human immunodeficiency virus who
      presented intestinal perforation due to mycobacterium tuberculosis. A resection
      of jejunum was performed with primary anastomosis. The postoperative course was
      further compromised by hepatic failure and the patient died 16 days after the
      initial surgery.

PMID- 9656759
TI  - [Primary torsion of the omentum: preoperative diagnosis with abdominal
      ultrasonography].

PMID- 9656760
TI  - [Complications in biliary surgery with laparoscopy: lithiasis of the residual
      cystic stump].

PMID- 9656761
TI  - [Acute cholestatic hepatitis secondary to flutamide].

PMID- 9656762
TI  - [Diagnosis of the supraelevator abscess].

PMID- 9656763
TI  - [Cholestatic hepatitis caused by captopril].

PMID- 9656764
TI  - Automatic classifiers for the interpretation of electrocardiograms.
AB  - The morphological diagnosis of ECGs is a pattern recognition procedure. The way
      the clinician does this is not clearly elucidated. Nevertheless, several models
      aimed at achieving identical results by automatic means are empleyed. While in
      the doctor's case this is not exactly so, the computer task for ECG
      interpretation comprises two distinct and sequential phases: feature extraction
      and classification. A set of signal measurements containing information for the
      characterization of the waveform is first obtained. These waveform descriptors
      are then used to allocate the ECG to one or more diagnostic classes in the
      classification phase. The classifier can embody rules-of-thumb used by the
      clinician to decide between conflicting ECG diagnosis and formal or fuzzy logic
      as a reasoning tool (heuristic classifiers). On the other hand, it can use
      complex and even abstract signal features as waveform descriptors and different
      discriminant function models for class allocation (statistical classifiers). More
      recently, artificial neural network techniques have also been used for signal
      classification. The authors review feature selection techniques and
      classification strategies, problems and methods of performance evaluation and
      results obtained by different classification approaches. A brief discussion of
      the relative merits of the two main types of ECG classifiers, logical and
      statistical, is included.

PMID- 9656765
TI  - [Thrombolysis in Portugal. Influencing the national reality].

PMID- 9656766
TI  - [Clinical manifestations and therapeutic of isolated infective endocarditis of
      the tricuspid valve].
AB  - We reviewed the records of patients admitted to our centre with the diagnosis of
      isolated tricuspid valve infective endocarditis and analysed the clinical
      presentation, etiopathogenic agent, echocardiographic features and therapeutic
      approach, namely the indication for cardiac surgery. Between 1988 and 1996, 11
      cases of confirmed tricuspid valve endocarditis were identified, corresponding to
      5% of the cases of endocarditis admitted to our centre in the same period. A
      predisposing factor was found in ten of the patients, half of them intravenous
      drug addicts and Staphylococcus aureus was the most frequent agent isolated.
      Fever and pleuro-pulmonary manifestations were predominant clinical features.
      Transthoracic echocardiography had a crucial role in the diagnosis and
      transesophageal echocardiography was important to characterize vegetations. Four
      patients underwent cardiac surgery, for persistent infection. In two cases,
      excision of the vegetations and ring annuloplasty was performed. In two patients
      not addicted to drugs, the tricuspid valve was replaced with a bioprosthesis,
      since the extension of the damage to the valve did not allow repair. One patient,
      with early endocarditis of a tricuspid bioprosthesis died before surgery was
      attempted.

PMID- 9656767
TI  - [Conn's syndrome. Primary hyperaldosteronism caused by adrenal gland adenoma].

PMID- 9656768
TI  - [Rationale for the pharmacologic treatment of cardiovascular diseases].
AB  - In what concerns the appropriate usage of drugs in the treatment of
      cardiovascular diseases, this paper provides a set of concepts and guidelines to
      aid the clinician in the choice of drug, the appropriate dose, the form of
      administration and the assessment of results. Therefore, the concepts of
      pharmacokinetics and pharmacodynamics which condition the administration regimen
      are also presented, as well as the notions of bioavailability, halflife and
      clearance in the light of the theory of the two compartments, quoting examples in
      the various pharmacologic groups currently used in cardiology. The main forms of
      administration and the respective indications are analysed and the concepts of
      tolerance, hypersensitivity and intolerance to a drug are also discussed. The
      importance of the major clinical trials in the assessment of the effects of drugs
      is supported, which consubstantiates the clinical decision based on scientific
      evidence. The notions of the efficacy and benefit of a treatment are presented,
      with examples of some recent clinical trials. The paper ends with a reference to
      the drug surveillance and cost-benefit studies.

PMID- 9656769
TI  - [Coronary angiography in the assessment of the probability of coronary artery
      disease].

PMID- 9656770
TI  - Cardiopulmonary exercise testing identifies low risk patients with heart failure
      and severely impaired exercise capacity considered for heart transplantation.

PMID- 9656771
TI  - [Impossibility to foresee ischemic recurrences after myocardial infarction].

PMID- 9656772
TI  - [Diastolic left ventricular dysfunction related with exercise in heart failure].

PMID- 9656773
TI  - [Chronic granulocytic leukemia (Ph+): among yesterday's myeloproliferative
      syndromes, today's chronic myeloid leukemias, and tomorrow's mature-element
      monocellular myelopathies].

PMID- 9656774
TI  - [The Philadelphia chromosome: from the gene to therapeutic methods].

PMID- 9656775
TI  - [Interferon alpha in the treatment of chronic myeloid leukemia. Promises,
      realities, and perspectives].

PMID- 9656776
TI  - [Allogeneic hematopoietic stem cell transplantation in chronic myeloid leukemia].

PMID- 9656777
TI  - [Autologous hematopoietic stem cell transplantation in chronic myeloid leukemia].

PMID- 9656779
TI  - [Advancing lung diseases--an epidemic which needs more alertness].

PMID- 9656778
TI  - [Cellular immunotherapy in chronic myeloid leukemia].

PMID- 9656780
TI  - [Stop treatment when the brain is dead].

PMID- 9656781
TI  - [Poliomyelitis--the beginning of the end].

PMID- 9656782
TI  - [The usefulness of clinical pulmonary examination in the diagnosis of bronchial
      obstruction].
AB  - In order to evaluate the usefulness of physical examination of the chest in
      diagnosing bronchial obstruction, 11 doctors recorded their findings in 692 adult
      chest patients. Spirometry was carried out after the physical examination. Two
      categories of patients were selected; patients with known or suspected pulmonary
      disease (n = 209) and patients who had consulted their doctors for other reasons
      (n = 483). Bronchial obstruction defined as either FEV1 < 70% predicted or FEV1 <
      70% of FVC, was found in 74 of the "pulmonary patients" and 55 of the "non
      pulmonary" patients. In the group of patients with bronchial obstruction, a
      pathological or less certain sign of chest disorder was found in 91% of the
      "pulmonary" patients, and in 42% of the "non-pulmonary" patients (p < 0.000001).
      Strenuous respiration was registered in 41% of the "pulmonary" patients with
      bronchial obstruction, whereas sensitivity was only 2% in the other group. Where
      there were two or more pathological chest findings, the risk of bronchial
      obstruction occurring was 66% among the "pulmonary" patients, as opposed to 37%
      in the "non-pulmonary" group. Physical examination of the chest appeared to be
      very useful in the detection of bronchial obstruction in patients with pulmonary
      symptoms, but of limited value in screening for bronchial obstruction.

PMID- 9656784
TI  - [Urinary incontinence in women in a geriatric ward].
AB  - 101 elderly female patients participated in a multidisciplinary programme for the
      diagnosis and management of urinary incontinence. Their median age was 81 years.
      83 patients had been incontinent for more than 12 months. In only 23 patients was
      incontinence recognised as a problem prior to admission, and 69 patients claimed
      that they had never received any treatment for their disability. Urge and mixed
      incontinence were found to be the most prevalent forms, based on symptoms and
      simple measurements. After assessment, one to six measures were implemented for
      each patient in order to counteract internal and external causes of incontinence.
      The patients were reviewed after 6-8 weeks. 60 patients claimed there was an
      improvement, including 20 who described themselves as "much improved", and seven
      who had become continent. It is suggested that a hospital stay may provide a
      suitable opportunity to undertake primary assessment and treatment of
      incontinence in elderly women.

PMID- 9656783
TI  - [Medication practice and personal knowledge of the disease among patients with
      obstructive lung disease].
AB  - 250 patients with obstructive lung disease who had attended an out-patient clinic
      were assessed after reporting on individual medication practices and their
      personal knowledge of the disease. 56% of the patients reported using two types
      of asthma medicine. The use of three, four, and five or more antasthmatica was
      reported by 26%, 9% and 5%, respectively. 90% had been prescribed an inhalation
      corticosteroid. Of these, one in five reported using it only when required,
      whereas in the age group 18-34 years the corresponding figure was one in three
      (34%). Regardless of what medication the patients were using, 20% reported that
      they often forgot to take it, 20% that they stopped taking it when their asthma
      improved, and 38% that they did not think about what time of the day they took
      their medicine. These practices of taking medication occurred more frequently in
      the young than in older patients. Practices did not vary with either a person's
      sex, duration of disease, or the patient's personal assessment of the seriousness
      of the disease. Patients with a higher level of education seemed to have greater
      knowledge of their disease than those with only secondary education, as was also
      the case with nonsmokers compared to smokers.

PMID- 9656785
TI  - [The effect of pelvic floor exercise on stress urinary incontinence].
AB  - Several randomised controlled trials have shown that pelvic floor muscle exercise
      has resulted in a 60-70% improvement or cure rate from stress incontinence. The
      aim of the present study was to assess whether these methods could be put into
      general use in a physiotherapy clinic in primary health care. 36 women, all with
      a diagnoses of stress urinary incontinence, mean age 49 (range 25-67 years),
      participated in the study. Before treatment they underwent vaginal examination to
      ensure there was proper pelvic floor muscle contraction. Pelvic floor muscle
      strength was assessed by vaginal pressure measurement. Urinary leakage was
      registered on a 13-item "leakage index", using a 5-point graded scale (1 = never
      leakage to 5 = always leakage). The women attended a six-month pelvic floor
      muscle exercise programme, training in groups led by a physiotherapist, and
      exercising at home with three series of 8-12 contractions a day. 12 patients
      reported to be cured, and 12 reported a significant improvement (67% in all).
      Five patients achieved some improvement, whereas in another five there was no
      change. None became worse. It is concluded that pelvic floor muscle exercises,
      under the guidance of trained physiotherapists, may be just as effective in
      clinical practice as in randomised controlled trials.

PMID- 9656786
TI  - [Penis fracture].
AB  - Fracture of the penis is a rare condition caused by blunt trauma to the erect
      penis resulting in tearing of the tunica albuginea. The injury occurs mainly
      during sexual intercourse or as a result of forceful manipulation. Two cases are
      described. Diagnosis is based on the patient's narrative and the clinical
      findings. One patient was treated by immediate surgery, while the other was
      treated by corrective surgery for his disabling posttraumatic penile deformity.
      Based on available literature and our own observations we recommend immediate
      surgical repair in order to avoid serious complications.

PMID- 9656787
TI  - [Measurement of exhaled nitric oxide. A new lung function test?].
AB  - Nitric oxide (NO) is a gas molecule produced endogenously in the lungs. It can be
      detected in the exhaled air of animals and humans. Nitric oxide can be generated
      in the air passages by a synthase which is induced in several cell types by
      exposure to proinflammatory cytokines. Its induction is blocked by
      glucocorticoids. An increased concentration of nitric oxide can be found in the
      exhaled air of patients with asthma and other inflammatory lung disorders. Gas
      analysers for measuring nitric oxide in exhaled air have recently been made
      commercially available. The test is non-invasive, simple to perform, and can also
      be used in patients with reduced lung function. The method seems to provide a
      unique non-invasive means of diagnosing and monitoring inflammation of the air
      passages, and in the future the test may become a useful tool in a clinical
      setting. Preliminary recommendations for measurements and technical
      standardization have recently been proposed by the European Respiratory Society.

PMID- 9656788
TI  - [Reflexes in brain-dead patients].
AB  - We report on a patient who suffered an acute, extensive intracerebral
      haemorrhage, leading to symptoms of cerebral herniation within a few hours. The
      clinical diagnosis of brain death was made based on a neurological examination,
      and an apnoea test eight hours after the haemorrhage. A few hours later the
      diagnosis was changed, as several reflexes reappeared. After six days mechanical
      ventilation was withdrawn, as the brain damage was considered so serious as to
      render further therapy futile. It was considered unethical to sustain therapy for
      a possible organ donation at a later date. A review of relevant the literature,
      however, shows that brain-dead patients may exhibit such varying degrees of
      autonomic and spinal reflexes as to cause confusion, thus delaying the physician
      in making a diagnosis. Often, an opportunity for organ donation is lost. Based on
      this review, we believe that our patient was indeed brain dead when the first
      diagnosis was made, and that a cerebral angiography should have been performed.
      Because organ donation is an important issue, the diagnosis of brain death must
      be definitive.

PMID- 9656789
TI  - [Adverse effects of zopiclone].
AB  - In 1994 zopiclone (Imovane), a cyclopyrrolon, was introduced in Norway as a new
      kind of hypnotic. In 1996 zopiclone had a 26% share of the hypnotic market. This
      review of relevant literature has revealed a lack of documentation on the adverse
      effects of zopiclone. The similarities between zopiclone and benzodiazepine
      hypnotics are more striking than the differences. The bulk of comparative
      research has been carried out with triazolam, a drug taken off the Norwegian
      market in 1991. With zopiclone there is less inhibition of psychomotor function
      the day after intake than with flunitrazepam. Zopiclone causes less subjective
      "hangover" than nitrazepam, but there is a similar inhibition of psychomotor
      function the day after intake, and in some cases greater addictive potential.

PMID- 9656790
TI  - [DNA repair enzymes and their genes].
AB  - DNA repair is of fundamental importance for protection of the genetic material
      against mutations in an interplay with mechanisms that regulate the cell cycle,
      gene expression, and programmed cell death. Defects in DNA repair, or in
      processes in tegrated with DNA repair, may give cells a hyper mutable phenotype
      that increases the likelihood of mutations in genes controlling cell growth. Two
      principally different DNA repair mechanisms are known; (a) direct repair of a
      damaged base by a single enzyme without using information from the complementary
      strand, and (b) excision repair, in which DNA containing the damage is removed
      and replaced by new DNA using DNA repair synthesis. Mechanisms for excision
      repair are complex and comprise base excision repair (BER), nucleotide excision
      repair (NER), mismatch repair (MMR), and recombination repair. In addition, the
      cell has mechanisms for repair of strand breaks. It has recently become clear
      that defective MMR is the cause of hereditary nonpolyposis colon cancer (HNPCC),
      and probably some 15% of the cases of sporadic colon cancer. There is also
      evidence that defective repair may be a primary cause of certain other forms of
      cancer.

PMID- 9656791
TI  - [Telomeres, telomerase and development of cancer].
AB  - The chromosome ends, telomeres, shorten during each cell division due to the
      inability of DNA polymerase to replicate the ends of linear chromosomes. The
      telomere length serves as a clock determining the remaining replicative capacity
      of the cell. After 50-100 doublings, the cell becomes senescent. Rarely, a cell
      overcomes the senescence blockade, and eventually becomes immortal. Cellular
      immortalisation is almost always accompanied by the expression of the enzyme
      telomerase, which synthesises telomeric DNA. Telomerase is present in
      approximately 85% of malignancies. The detection of telomerase activity in cancer
      cells represents a possible cancer diagnostic and prognostic tool, and telomerase
      inhibition may become a novel therapeutic strategy in cancer patients.

PMID- 9656792
TI  - [Is it justifiable to put the destiny of scholarship recipients into the hands of
      their supervisors?].

PMID- 9656793
TI  - [Is treatment of lung cancer characterized by nihilism?].

PMID- 9656795
TI  - [Traditional and modern medicine in Ngami].

PMID- 9656794
TI  - [Mix-up of drugs].

PMID- 9656796
TI  - [Transcendental mediatation, stress reduction and hypertension].

PMID- 9656798
TI  - [Increased danger for accidental nuclear war].

PMID- 9656797
TI  - [Do house mites eat plastics--or what?].

PMID- 9656799
TI  - [Do physicians have better sight than others?].

PMID- 9656802
TI  - [The tobacco industry--major enemy of health care].

PMID- 9656803
TI  - [Research results and discoveries--who owns what?].

PMID- 9656804
TI  - [Quality assurance of back surgery].

PMID- 9656805
TI  - [Quality assurance of back surgery. A follow-up of 350 patients treated for
      sciatica by means of survival analysis].
AB  - 350 patients underwent a follow-up 2-16 years after back surgery. The aim was to
      find quality indicators, such as frequency of complications, recurrences and
      reoperation, in addition to establishing postoperative status and patient
      satisfaction. The complication rate was 9.7%. Most complications were not
      serious, and there was no mortality. We found a cumulative recurrency rate of 18%
      and a cumulative reoperation rate of 12%. Women had significantly better long
      term results than men, psychosocial problems being a strong negative predictor.
      Questionnaires revealed that 76% of the patients were satisfied, whereas 22% were
      not. Postoperatively, 59% reported a persistent, but usually slight back problem.

PMID- 9656806
TI  - [Paresis of the superior oblique eye muscle].
AB  - Congenital or acquired palsy of the superior oblique eye muscle presents a
      clinical picture which is consistent and recognizable. The diagnosis is based
      upon two clinical findings: hypertropia of the affected eye with a greater than
      normal vertical deviation in adduction, and an increase of the hypertropia when
      tilting the head towards the affected side (positive Bielschowsky test). In the
      majority of cases the dominant feature of the clinical picture is overreaction of
      the ipsilateral inferior oblique. We have retrospectively examined 22 patients
      with superior oblique palsy who underwent surgery. Median follow-up time was
      three months. 20 (91%) of the patients were operated primarily by performing a
      recession of the ipsilateral inferior oblique muscle. Additional surgery had to
      be performed on five patients. The final postoperative examination showed the
      result to be a success in 19 (86%) of the patients, judged on relief of symptoms
      and objective measurements. We conclude that in the majority of cases surgical
      treatment of superior oblique palsy by recession of the ipsilateral inferior
      oblique gives good results.

PMID- 9656807
TI  - [Use of antipsychotic drugs in a long-term care institution. Experiences with
      implementing clinical guidelines].
AB  - Anti-psychotic drugs (neuroleptics) are useful for treating psychoses. However,
      non-psychotic patients, particularly patients with a deviant behaviour pattern,
      are often also treated with anti-psychotic drugs. The drugs may induce serious
      side-effects and should only be used on strict indications and at the lowest
      possible dosage. In a nursing home for deaf people with additional handicaps we
      introduced clinical guidelines for the use of anti-psychotic drugs and recorded
      their use during a two-year period. We found there was a reduction in the number
      of patients taking anti-psychotic drugs (from 32/54 to 26/54, p = 0.03), as well
      as a decrease in dosage per user (from median 2.4 mg to 1.7 mg equivalents of
      haloperidol, p = 0.05). Both the number of patients who were given depot
      injections and the number of different anti-psychotic drugs per patient were
      reduced. We conclude that it is possible to reduce the use of anti-psychotic
      drugs in institutions where long-term care is provided for disabled people.

PMID- 9656808
TI  - [Forensic psychiatric examinations of the mentally retarded].
AB  - 3,343 forensic psychiatric examinations were recorded in Norway from 1980 to
      1996. 294 patients were diagnosed as mentally retarded. The annual number of
      mentally retarded persons increased during the observation period, but the
      relative percentage remained stable. The majority of the retarded persons being
      discussed had been charged with sexual felony, and some with arson. About half
      had previous convictions. Few had problems with alcohol or other intoxicants.
      Every fourth retarded person examined was considered not only to be mentally
      retarded, but also to suffer from other psychiatric disorders. We discuss to what
      extent deinstitutionalization of retarded persons and the accompanying social
      isolation they experience could contribute to the increase in maladaption and
      criminal behaviour. It is stressed that many of the sexual felonies may be
      explained by the fact that the mentally retarded are mentally immature.

PMID- 9656809
TI  - [Depression and Down syndrome].
AB  - Emotional and behavioural disorders are frequent complications of mental
      retardation that often go unrecognised or untreated. We describe a 13-year old
      girl with Down's syndrome and depressive illness who responded well to paroxetin.
      The importance of organizing comprehensive health provision for children with
      mental retardation in a way that focuses both psychiatric and physical illness is
      emphasised.

PMID- 9656810
TI  - [Venous thromboembolism in connection with physical restraint].
AB  - A 29-year old man was admitted to an emergency psychiatric ward because of
      exacerbation of a chronic paranoid schizophrenia. He was restrained after
      arrival, and seven days later a deep venous thrombosis and a pulmonary embolism
      were diagnosed. No haematological predisposing factors (coagulation inhibitor
      deficiency, activated protein C resistance, or antiphospholipid antibodies) were
      identified, except for a questionable borderline increase of the fibrinolysis
      inhibitor PAI-1, and combined type II hyperlipidaemia. During the last 15-20
      years, there has been a considerable reduction in the use of restraint and
      seclusion in Norway. The use of seclusion and restraint may be effective in
      preventing injury and reducing agitation, but these procedures may also have
      harmful physical, and in particular psychological side-effects. To our knowledge,
      this is the first report to demonstrate an association between venous
      thromboembolism and physical restraint. Immobilisation is a well-known risk
      factor for thrombophlebitis, and special attention should be paid to this problem
      on psychiatric wards. However, until more is known about thrombosis in relation
      to restraint, it is not advisable to recommend prophylactic treatment of
      thrombosis.

PMID- 9656811
TI  - [Children and adolescents with ulcerative colitis and Crohn disease].
AB  - The diagnosis and treatment of children and young people with ulcerative colitis
      and Crohn's disease follows the same guidelines as for adults, but several
      important and unique problems related to the diseases in young age groups deserve
      attention. Since ulcerative colitis and Crohn's disease are relatively rare at a
      young age, there is often a lack of awareness among people in general, parents
      and general practitioners. There is therefore often an unnecessarily long delay
      before the young patient is seen by a general practitioner and then referred to a
      specialist centre where the diseases can be properly diagnosed, evaluated and
      treated. Chronic gastrointestinal symptoms caused by inflammatory bowel disease
      at an age where physical and mental growth are at a peak could result in serious
      negative effects not only on young patients' physical and mental development, but
      also on their self-esteem. The diseases adversely affect the quality of life of
      many young patients and their families and are a source of anxiety, emotional,
      behavioural, and psychological morbidity. Patients' organisations can help by
      providing additional information and support through special groups for young
      patients with inflammatory bowel disease.

PMID- 9656812
TI  - [Can we rely on self-reported smoking habits?].
AB  - The reliability of self-reporting on smoking habits has been evaluated by
      comparing the reported smoking habits with the concentration of serum
      thiocyanate, which is higher in smokers than in non-smokers and increases with
      increasing cigarette consumption. When a smoker stops smoking, the level of serum
      thiocyanate decreases and falls to the level observed in non-smokers after about
      one month. When the questions asked about smoking were neutral, the reported
      smoking habits were generally reliable. However, in cases where the questions
      asked and the interview situation could be regarded as unpleasant, the reported
      smoking habits were not always correct. Some smokers underreported the number of
      cigarettes they smoked on a daily basis and some of them denied smoking
      altogether.

PMID- 9656813
TI  - [Who gives up smoking? Results from the health surveys in Finnmark in 1977/78 and
      1987/88].
AB  - In order to develop effective smoking cessation programmes, it is important to
      understand why people stop smoking. This study is based on data from two
      population-based health surveys carried out in the northernmost county of Norway
      in 1977-78 and 1987-88. 6,254 men and 6,404 women smokers participated in the
      survey. For both surveys questionnaires were used to collect information on
      smoking habits, sociodemographic variables, various diseases, symptoms, health
      related behaviours, and social network. Ten years later 19.3% of the men and
      16.0% of the women had stopped smoking. The primary factors for giving up were: a
      short history of smoking, older age, having non-smoking family and friends, and
      acquiring a smoking related disease during the period. Health promoting
      behaviours, such as low consumption of coffee, alcohol, butter and margarine,
      also increased the chances of giving up smoking. Developing smoking related
      symptoms, such as a morning cough, or coughing up mucus in the mornings,
      predicted continuous smoking. Future health promotion programmes should be
      targeted at young smokers and persons with smoking related diseases; and efforts
      should probably be directed towards lifestyle with the aim of modifying general
      attitudes to health.

PMID- 9656814
TI  - [The use of tobacco and smoking habits--is Norway lagging behind?].
AB  - A comparative analysis of smoking habits, based on data from three different
      sources, shows that the present level of tobacco consumption in Norway is at a
      mid-Nordic level, but lower in a European perspective. There has been a 25%
      decline in per capita consumption of tobacco since the mid-1970s, and the
      decrease has been most pronounced during the 1990s. The current rate of decline
      is the same as in the other Nordic countries. The prevalence of smoking among men
      is at present lower in Norway than in most European countries outside the Nordic
      ones. Since the mid-1950s, the prevalence of daily smoking among Norwegian men
      has decreased from approximately 70% to 35% in 1997. However, within the last ten
      years the decline has levelled out and smoking among men has been stable in
      recent years. Smoking among women is more widespread in Norway than in most
      European countries. The number of female smokers reached a peak around 1970.
      Since the 1970s, the prevalence of smoking among women has been stable. The
      prevalence of daily smoking in the age-group 16-24 years is currently at a mid
      European level. However, the decline observed during the late 1970s and the first
      half of the 1980s does seem to have levelled out during the 1990s.

PMID- 9656815
TI  - [Passive smoking and risk of cancer].
AB  - During the last two decades there have been frequent discussions as to whether
      passive smoking causes cancer, or not. It is difficult to carry out satisfactory
      studies on this issue, partially because any increased risk of cancer seems
      modest. The tobacco industry has not only attempted to make the public aware of
      studies which conclude that passive smoking is harmless, but it has also tried to
      keep alive the discussion as to whether exposure to passive smoking is harmful,
      or not. A large number of studies has been carried out on the possible impact
      passive smoking may have on the risk of lung cancer, and it seems justifiable to
      conclude that passive smoking does increase the risk of this type of cancer. For
      other types of cancer too few studies have been performed to draw any firm
      conclusions.

PMID- 9656816
TI  - [Molecular biology diagnosis of sarcoma].
AB  - Sarcomas are a heterogeneous group of malignant tumours, primarily in connective
      and supportive tissues, that can be difficult to distinguish from other tumour
      types. Recent knowledge of gene rearrangements resulting from specific
      translocations in several groups of sarcomas now enables the molecular diagnosis
      of these subtypes. Increasing knowledge of molecular defects that may be of
      importance to therapy response and prognosis may in the future become important
      tools in the clinic, although these tumours are relatively rare, making it
      difficult to investigate large numbers of comparable groups of patients.

PMID- 9656817
TI  - [Diagnostic molecular biology in prostatic cancer].
AB  - Studies of molecular genetic changes in prostate carcinomas are slowly improving
      our understanding of the biological process which leads to a normal prostate
      epithelial cell becoming an adenocarcinoma cell with invasive and metastatic
      properties. Carriers of germ-line mutations in still unidentified prostate cancer
      susceptibility genes, one of which has been localised to chromosome arm lq, seem
      to be particularly prone to develop the disease. The susceptibility genes have to
      be identified and the effects of carrier detection evaluated before genetic
      testing for prostate cancer predisposition can be performed in a clinical
      setting. The identification of specific molecular genetic changes in prostate
      carcinomas may become clinically useful diagnostic and prognostic tools. An
      improved understanding of the molecular genetic mechanisms underlying the
      development of prostate cancer may eventually yield novel therapeutic strategies,
      attacking specific genetic changes in the prostate carcinomas.

PMID- 9656818
TI  - [Diagnostic molecular biology in solid tumors--thyroid gland].
AB  - Thyroid cancer is not a common disease. It includes tumour types of great
      diversity in clinical course and molecular basis. Mutations of TSH-receptor,
      rearrangements of ret proto-oncogene, and altered expression of other tyrosine
      kinase growth factor receptors are characteristics of the follicular neoplasias
      and papillary carcinomas, while undifferentiated tumours harbour p53 mutations.
      Knowledge acquired to date has led to an increased understanding of thyroid
      growth and tumour development, but it has had no significant impact on diagnostic
      and treatment measures. On the other hand, the C-cell derived medullary
      carcinomas include familial cases where identification of germ-line ret mutations
      provides the basis for prophylactic thyroidectomy in affected individuals.

PMID- 9656819
TI  - [The psychiatric record].

PMID- 9656820
TI  - [Aimed health check-ups can be justified].

PMID- 9656821
TI  - [California Proposition 99--an example to follow?].

PMID- 9656822
TI  - [Estrogen replacement is better than alendronate].

PMID- 9656823
TI  - [Causes of social inequality in relation to health].

PMID- 9656824
TI  - [Self perception of the elderly].

PMID- 9656825
TI  - [New Danish and international rules on research ethics].

PMID- 9656826
TI  - [Treatment of pain via a cervical epidural catheter].
AB  - Cervical epidural anaesthesia (CEA) is a method suitable for regional anaesthesia
      of the upper extremity. CEA seems useful for postoperative pain relief after
      surgery in the shoulder region or both upper extremities, especially when the
      postoperative pain relief must be long lasting (days), and when it is desirable
      that the patient be able to actively move his affected joints during
      rehabilitation. Potential side effects of the method are respiratory- and
      haemodynamic changes. Thus, CEA is inappropriate for patients with severe
      respiratory disease, and in patients for whom extensive sympathetic block may
      prove disastrous (e.g. congestive heart failure, hypovolaemia).

PMID- 9656827
TI  - [New techniques in neurosurgery].
AB  - Society demands for exactness and low complication rates of surgical treatment
      are high. Surgical training in the apprentice manner has been significantly
      reduced in Denmark since 1981 and e.g. the ability to visualize in three
      dimensions among younger neurosurgeons has diminished. Computer technology now
      makes it possible to create 3-D images that with incorporation of functionality
      leads to a faster and better understanding of neuroanatomy. In addition--for the
      sake of precision--true robotic instrumentation and navigational instruments have
      been introduced. The technological investments are compensated by reduced costs
      due to operative complications. A prerequisite for these developments are a close
      collaboration between medical doctors and engineers, keeping the respect for
      humanity intact. A survey of developmental areas in the neurosurgical techniques
      of today is given.

PMID- 9656828
TI  - [Juvenile neuronal ceroid lipofuscinosis].
AB  - Neuronal ceroid-lipofuscinosis is a group of neurodegenerative diseases which are
      characterized by an abnormal accumulation of lipopigment in neuronal and
      extraneuronal cells. The diseases can be differentiated into several subgroups
      according to age of onset, the clinical picture, neurophysiological and
      neuropathological abnormalities and ultrastructural studies documenting different
      profiles of the lipopigment. Several eponyms have been used in the designation of
      the diseases. Latest, an international designation abbreviated CLN has been
      recommended, with the addition of figures according to the subtypes. The most
      common type in Denmark is CLN3, also called Spielmeyer-Vogt's disease. The
      incidence is 1.6 per 100,000. It is characterized by slowly progressing
      behavioral and visual symptoms that start when the child is about four to nine
      years old. During the second decade of life, the disease is accompanied by
      seizures and severe psychomotor deterioration. Most patients die before the age
      of 30 years. Recently, it has been shown that this type of CLN disease is due to
      a mutation in a gene located on chromosome 16 (16p 12.1). A brief description of
      the other subtypes of CLN is given.

PMID- 9656829
TI  - [Enzyme substitution in Gauscher disease].
AB  - Gaucher's disease is the most frequent inherited lysosomal storage disorder,
      displaying hepato-splenomegaly, thrombocytopenia, anaemia, and bone pain as
      characteristic features. Substitution with the modified enzyme alglucerase has
      revolutionized the treatment and prognosis of Gaucher's disease. Treatment in
      general and current trends in enzyme substitution therapy in particular are
      discussed.

PMID- 9656830
TI  - [Sequelae after polio--a review].
AB  - Poliomyelitis has almost been eradicated world-wide, but during the last decades
      polio survivors have noted new problems: late effects of polio and post-polio. In
      Denmark, 7-8000 polio survivors are disabled by poliomyelitis. Late effects of
      polio, defined as onset of new symptoms decades after the acute poliomyelitis,
      include fatigue and overuse muskuloskeletal problems. Post-polio is a sub
      category of the late effects of polio and related to impaired neuro-muscular
      function with unexpected onset, which is not caused by the patient's age. Post
      polio is a clinical diagnosis and cannot be verified by a definitive test. The
      dysfunction of the muscles is caused by loss of motor neurones and reduced
      neuromuscular reserve capacity, in combination with a disturbed balance between
      the ongoing reinnervation and denervation at the expense of the reinnervation.
      Many polio survivors suffering from late effects of polio have a need for
      multidisciplinary rehabilitation, physiotherapy, reconstruction of orthosis,
      social counselling, modifications to the home and individual aids.

PMID- 9656831
TI  - [Neurosurgical treatment of trigeminal neuralgia. A comparative study of alcohol
      block, neurectomy and electrocoagulation].
AB  - The objective was to assess the present condition of patients previously treated
      with neurosurgical procedures for trigeminal neuralgia (TN). Between 1976 and
      1991, 383 patients were treated for TN at the Department of Neurosurgery,
      Hvidovre Hospital. The latest surgical intervention performed was radiofrequency
      coagulation (64%), neurectomy (18%), alcohol block (16%), trigeminal tractotomy
      (1%), and microvascular decompression (1%). Questionnaires were sent to 316
      patients treated neurosurgically for trigeminal neuralgia during the 16 year
      period. After radiofrequency coagulation, neurectomy and alcohol block, 83, 51
      and 42% respectively experienced a pain free postoperative period. At present 49,
      17 and 18% were without pain and 33, 21 and 36% had less pain compared with the
      preoperative state. Sequelae were described in 65, 57 and 49% of the patients.
      The four most common sequelae were hypaesthesia, paraesthesia, eye complaints,
      and dysaesthesia. If relevant pharmacotherapy has been tried without benefit,
      radiofrequency coagulation may still be considered as a treatment of trigeminal
      neuralgia.

PMID- 9656832
TI  - [Prolapsed cervical intervertebral disk in professional drivers in Denmark 1981
      1990].
AB  - The aim of this study was to estimate the risk of being hospitalized due to
      prolapsed cervical interverteral disc among male professional drivers in Denmark.
      A cohort consisting of all economically active persons in Denmark, identified
      January 1981, gives information on the most important occupation during 1980. The
      cohort was followed for ten years. Additional data on occupational exposures were
      extracted from a national survey. Occupational groups such as bus and taxi-cab
      drivers were found to have an increased risk, of cervical prolapse as did the
      group of professional drivers as a whole.

PMID- 9656833
TI  - [The prognostic value of thrombocytosis in patients with primary lung cancer].
AB  - The prognostic information provided by platelet counts was studied in 1115
      patients with primary lung cancer and in 550 control patients with benign lung
      disorders. Patient records were retrospectively reviewed regarding histological
      tumour type, TNM stage, thromboembolic episodes and survival. The prevalence of
      thrombocytosis (platelet count > 400 x 10(9)/l) in patients with lung cancer was
      32.1% vs. 6.4% in controls (p < 0.0001). Platelet counts increased with TNM stage
      (p < 0.0001). Patients with thrombocytosis had a shorter survival than patients
      with normal platelet count (p < 0.0001). Thrombocytosis was a predictor of short
      survival also when adjusted for tumour type, sex, age, and TNM stage (p < 0.001).
      The platelet count and the frequency of thrombocytosis declined after tumour
      resection (p < 0.0001). Thrombocytosis was not associated with thromboembolism.
      In conclusion, thrombocytosis is a clinically significant prognostic indicator
      regarding survival in patients with primary lung cancer.

PMID- 9656834
TI  - [Surgery for phimosis with Plastibell. A follow-up study].
AB  - Fifty-three boys were interviewed 11 years (9-14 years) after an operation for
      phimosis using the Plastibell technique. The interview concentrated on the
      cosmetic result, sexual function and late complications. Seventeen patients (31%)
      experienced cosmetic complications, and 11 patients (21%) claimed to have
      experienced psycho-social problems due to the appearance of the penis after the
      operation. Nonetheless an overall of 44 patients (83%) were fully
      satisfied/satisfied with the cosmetic result. Four patients (8%) claimed to have
      pain or discomfort on erection or intercourse. One patient (2%) was re-operated
      three years after the primary operation because of a recurrence of the symptoms.
      Overall 48 patients (91%) were fully satisfied or satisfied with the result after
      the operation. In conclusion we find the Plastibell procedure to be a safe and
      reliable method in treating phimosis. There are some minor technical pitfalls
      that have to be addressed in learning the technique, but performed in trained
      hands, the technique offers a very high satisfaction rate at long term follow-up.

PMID- 9656835
TI  - [Indications for cataract surgery in Denmark in 1980 and 1992. Results from the
      Danish Cataract Surgery Outcomes Study].
AB  - In Denmark the number of cataract extractions has increased to 350% from 1980 to
      1991. During the same period the elderly population at risk has only increased to
      117%, and thus cannot account for the large increase in the number of
      extractions. In order to investigate whether more comprehensive clinical
      indications could be a possible explanation, we compared pre-operative visual
      acuity and visual impairment in two consecutive samples of Danish cataract
      surgery patients obtained in 1980 (n = 73) and in 1992 (n = 270). Criteria for
      inclusion were similar and both samples were representative for the whole
      country. During the period mean pre-operative visual acuity increased from 0.04
      to 0.16 in the eye enlisted for surgery (p < 0.001). Visual functional impairment
      could be compared by using the same questionnaire for patient interview in 1992
      as was used in 1980. In 1992, the degree of impairment was significantly less for
      reading, outdoor orientation and self care activities. A change in surgical
      threshold or clinical indications for surgery appears to be a major contributing
      factor to the large increase in surgical rates.

PMID- 9656836
TI  - [Gaucher disease type 1--therapeutic results of enzyme substitution].
AB  - Gaucher's disease is the most common inherited lysosomal storage disorder,
      displaying hepato-splenomegaly, thrombocytopenia, anaemia and bone pain as
      characteristic features. Substitution therapy with a modified enzyme alglucerase
      has revolutionized the treatment and prognosis of Gaucher's disease. The first
      Danish patients treated with alglucerase are reported.

PMID- 9656837
TI  - [Angiotensin-converting enzyme inhibitor dosage in chronic heart insufficiency].

PMID- 9656838
TI  - [The possibility of driving under influence among traffic offenders. II].

PMID- 9656839
TI  - [Serotonin antagonists in the treatment of postoperative nausea and vomiting].

PMID- 9656841
TI  - Occlusal vertical dimension: what is the controversy?

PMID- 9656840
TI  - An esthetic alternative to conventional porcelain-fused-to-metal crowns.

PMID- 9656842
TI  - Occlusal vertical dimension: alteration concerns.
AB  - This article exposes common myths supported by restorative dentists that serve to
      limit our potential for achieving more favorable results. The need to alter
      occlusal vertical dimension (OVD) signifies a number of concerns that include:
      bite force measurements, rest vertical dimension, effect on temporomandibular
      joint loading, effect on tooth loading, and neuromuscular adaptation/stability.
      There appears to be sufficient scientific support to conclude that alteration of
      OVD can provide a biologically compatible adjunct to treatment. These alterations
      can improve dentofacial esthetics, create improved visual proportions in facial
      height, and provide an important treatment modality for force management of the
      masticatory system.

PMID- 9656843
TI  - Facially generated occlusal vertical dimension.
AB  - Facial height has a profound effect on attractiveness. Occlusal vertical
      dimension (OVD) determines facial proportion at maximum intercuspation and
      influences facial dimension at rest. Deficient facial height visibly compromises
      optimal facial beauty. This article explores the dependent relationships between
      the OVD and facial esthetics, and discusses the role of facial analysis in
      determining an optimal OVD.

PMID- 9656844
TI  - Vertical facial skeletal dysplasias: the oral surgical connection.
AB  - Oral surgery can open new vistas of treatment for patients with vertical
      abnormalities of the face, jaw, and teeth. An interdisciplinary approach is
      critical, however, incorporating the insights and skills of restorative,
      orthodontic, periodontal and surgical practitioners working together as a team. A
      complete diagnosis is the key to any successful treatment plan. Because surgery
      is instantaneous and relatively irreversible, the treatment team needs to be
      aware of the impact of surgical repositioning of the maxilla and mandible on the
      other treatment modalities, so the ultimate prosthetic objectives for the patient
      may be facilitated and not hindered. The craniofacial complex is more adaptable
      to vertical changes than is often realized. When a correct "palate" of therapies
      is chosen, the desired results can be achieved despite the complexities of
      symptoms and treatment. A desirable result must include optimum function,
      stability, and facial harmony.

PMID- 9656845
TI  - Are speech-based techniques for determination of occlusal vertical dimension
      reliable?
AB  - This article describes the most common techniques used for clinical assessment of
      occlusal vertical dimension (OVD), and includes a discussion of recently
      published data which strongly suggest that techniques based on sibilant sounds
      are not as reliable as they are generally regarded to be for the evaluation of
      OVD. Assessment and establishment of OVD are sometimes difficult in edentulous
      patients, as well as for dentate patients with multiple missing posterior teeth
      and/or extensive wear. Techniques based on the use of interocclusal distance and
      facial soft-tissue contours, along with techniques based on sibilant sounds, are
      discussed. Although absolute scientific support for any technique is lacking, the
      careful use of the techniques described in this article, in combination, will
      usually result in the establishment of a clinically acceptable OVD for most
      patients.

PMID- 9656846
TI  - Esthetics and vertical tooth position: orthodontic possibilities.
AB  - Throughout the 1990s, esthetic dentistry has become a prominent part of the
      treatment protocol of most dentists. Patients have become more conscious of the
      benefits of a beautiful smile and are willing to invest time and money to improve
      the appearance of their teeth. Many of these patients can be treated with routine
      restorative procedures (crowns, composites, laminates) to achieve the desired
      results. However, some patients have problems with tooth position that create
      significant discrepancies in gingival levels which can compromise the esthetic
      result of restorative dentistry. Prerestorative orthodontic therapy can often
      resolve these tooth position problems and enhance the esthetic restoration. This
      article describes the indication, methods, and results achieved when orthodontics
      preceded restorative dentistry in the treatment of various esthetic challenges.

PMID- 9656848
TI  - Leadership makes a difference.

PMID- 9656847
TI  - The effect of sodium lauryl sulfate on recurrent aphthous ulcers: a clinical
      study.
AB  - This study measured the incidence of recurrent aphthous ulcers during the use of
      dentifrices with and without sodium lauryl sulfate (SLS). A single-blind,
      crossover design was used. A statistically significant reduction in recurrent
      aphthous ulcers was observed during 2 months' use of SLS-free dentifrice compared
      to 2 months' use of the SLS-containing dentifrice. These results support the
      results of an earlier independent study, and suggest that use of an SLS-free
      dentifrice should be considered for individuals suffering from recurrent aphthous
      ulcers.

PMID- 9656849
TI  - Clinical evaluation of two carbamide peroxide tooth-whitening agents.
AB  - A blinded study was conducted to evaluate the efficacy and safety of a dentist
      prescribed, accelerated carbamide peroxide tooth-whitening system. Fifty-one
      patients with discolored teeth completed a clinical trial using an overnight
      bleaching regimen. One group used an experimental bleaching (whitening) regimen
      with 10% carbamide peroxide bleaching paste, and another group used the Colgate
      Platinum Professional Overnight Whitening System. The study included an initial 1
      week control/compliance phase using a placebo gel, followed by a 1-week active
      phase using the assigned bleaching agent. The shade of each participant's
      maxillary anterior teeth was evaluated by 2 trained and calibrated evaluators at
      the start of the control/compliance phase, the beginning of the active phase, and
      days 3, 5, and 7 of the active phase. A value-oriented Vita shade guide with 16
      rankings was used to measure color changes, and the number of shade guide units
      of change (delta sgu) was calculated. Potential side effects, such as tooth
      hypersensitivity and gingival irritation, also were assessed at each recall
      examination, as well as recorded by the patients in their daily diaries. At the
      end of the 7-day active phase, the mean delta sgu for the group using the
      experimental bleaching agent was 7.1 +/- 2.4, and for the Colgate Platinum
      Overnight group, the delta sgu was 7.5 +/- 2.2. There were no statistically
      significant (p > or = 0.05) differences between the results of both groups at the
      0-, 3-, 5-, and 7-day evaluations. After 7 days, the change in shade guide units
      for both groups ranged from 3 to 13 units, far exceeding the minimum required
      change by the American Dental Association Guidelines (delta sgu = 2 units) for
      demonstrating efficacy. There was no statistical difference in the whitening
      achieved at day 5 vs. day 7 for either tooth-whitening group. There were no
      notable changes in any gingival, bleeding, or plaque indexes for the 50 patients
      completing the active phase. The number of days of mild tooth sensitivity during
      the active phase was 0.9 +/- 1.3 days for the experimental agent group and 1.1 +/
      1.5 days for the Colgate Platinum group.

PMID- 9656850
TI  - Principles of speech and their application to dental reconstruction.

PMID- 9656851
TI  - Shade selection: problems and solutions.
AB  - This article introduces shade selection as an act of communication rather than a
      quasi-science that has failed for generations. The use of three simple items: the
      Pensler Shield, the Kodak Color Viewing Light Selector Card (P3-180), and a
      patient-oriented prescription form solve the major problems in shade selection.
      Shade selection must be taught with an understanding of the psychology of vision
      and a communication of what you think you see.

PMID- 9656852
TI  - Revised endocarditis prophylaxis guidelines: signal of a new era? American Heart
      Association.

PMID- 9656853
TI  - Dentoalveolar surgical sequelae.
AB  - Most general dental practitioners perform dentoalveolar surgery as part of their
      practice. Postoperative sequelae can cause great concern for patients and undue
      stress for the general practitioner. This article explains the importance of
      patient education with regard to these sequelae and discusses standard treatment
      modalities the practitioner can employ if they should arise.

PMID- 9656854
TI  - The prevention and management of the broken curet.
AB  - With repeated sharpening or improper technique, a curet tip may break inside a
      periodontal pocket. This creates a problem for the clinician because the tip
      usually cannot be seen or felt. This article offers suggestions that can prevent
      such breakage. The include instrument selection and application, appropriate use
      of force, and proper sharpening. The article also describes a pair of magnetic
      instruments that can remove a loose fragment when curet fracture occurs and
      explains how the instruments are used.

PMID- 9656855
TI  - To tame the pain?
AB  - Pain is still one of the most common reasons given by patients for avoiding
      dental care. Dental pain was identified as one of the most common pain complaints
      a national survey of pain in the US population. Although pain associated with
      dentistry encompasses intraoperative pain and pathologic pain as a result of
      dental neglect, it is likely that some of the aversion toward dentistry is a
      result of pain that occurs in the postoperative period.

PMID- 9656856
TI  - An evaluation of the iatrosedative process for treating dental fear.
AB  - The iatrosedative process is an interpersonal-cognitive technique by which
      fearful patients are calmed by the behavior, attitude, and communicative stance
      of the dentist. The process consists of an iatrosedative interview and a clinical
      encounter. In our study, 58 fearful dental patients were assigned to 1 of 3
      treatment groups. The Corah Dental Anxiety Scale was administered at admission to
      the clinic, immediately after the iatrosedative interview or standard interview,
      and again after the first and second clinical encounters. Participants who
      received the iatrosedative interview had a significantly greater reduction in
      dental anxiety after the interview than those who received the standard
      interview. After the two clinical encounters, however, the difference in anxiety
      reduction between the two groups was not significant. In addition, there was no
      significant difference in anxiety reduction between iatrosedative participants
      who had the same dentist for both the interview and the clinical encounter and
      participants who had different dentists for each part of the study. It is
      concluded that an iatrosedative interview is more effective than a standard
      dental interview in decreasing anxiety.

PMID- 9656857
TI  - Soft-tissue considerations in esthetic reconstruction.

PMID- 9656858
TI  - A morphometric analysis of the furcation region of mandibular molars.
AB  - This study examined furcation dimensions and morphology in first and second
      mandibular molar teeth. One hundred thirty-four extracted human mandibular molars
      with divergent roots were selected. Teeth were viewed at 7X magnification on a
      dissecting microscope interfaced with a computer equipped with a state-of-the-art
      histomorphometry software program. Various aspects of furcation anatomy were
      measured and recorded. Data were examined by using analysis of variance for all
      paired comparisons. For nonparametric data, the Kruskal Wallis test was used.
      Results indicated that 61.94% of buccal and 50.75% of lingual molar surfaces
      presented with cervical enamel projections (CEPs), with the highest frequency
      noted in second molars. CEPs ranged from 0.98 mm to 1.33 mm, whereas root trunk
      heights varied between 2.23 mm and 2.93 mm. Generally, lingual molar surfaces had
      longer root trunks when compared to buccal surfaces. Root separation increased by
      approximately 0.5 mm at each 1-mm increment apical to the furcal roof. This study
      provides new information regarding the furcal anatomy of mandibular molar teeth
      and supplements previous reports that suggest the CEP is a common problem which
      must be addressed by clinicians when treating molar teeth.

PMID- 9656859
TI  - The importance of dentistry in the differential diagnosis of a medical disorder.
AB  - This is a case report of a patient presenting to our clinic with a chief
      complaint of occlusal changes, but no clear-cut diagnosis of local origin could
      be found. The patient later was diagnosed with acromegaly. This rare systemic
      disease, caused by a slow-developing tumor of the pituitary gland, induces
      changes in various vital organs. Among them is a change in occlusion that can
      bring the patient to the dentist first. Dental professionals may be the first
      health care providers to see the signs and symptoms of acromegaly, and thus have
      the first opportunity to correctly diagnose this serious disease. This case
      demonstrates the importance of taking a thorough medical history and making a
      careful diagnosis before any dental treatment is recommended or undertaken.

PMID- 9656860
TI  - Direct reimbursement.

PMID- 9656861
TI  - Using a precision-metered injection system to minimize dental injection anxiety.
AB  - In this study, 90% of dental patients reported being at least mildly anxious
      about receiving dental injections. A new precision-metered injection system has
      been developed that can greatly increase the probability of painless injections
      of local anesthetic. Surveys were administered to patients to quantify their
      fears of dental injections and to measure the desensitization effect of using the
      new injection system. According to survey results, fear levels decreased
      significantly when the new technology was used.

PMID- 9656862
TI  - Management of the gingival sulcus in fixed prosthodontics: a literature review
      and treatment protocol.
AB  - This review of the fixed prosthodontics and periodontology literature illustrates
      the influence of various factors on the health of the periodontium during and
      after fixed prosthodontic treatment. This article describes four categories of
      marginal finish lines for fixed prosthodontic restorations relative to the
      gingival margin and the epithelial attachment. The management of each category
      from both the periodontal and prosthodontic prespectives is also discussed.

PMID- 9656863
TI  - The effect of dental rehabilitation on the body weight of children with failure
      to thrive: case reports.
AB  - Four case reports of children with nursing caries and failure to thrive are
      presented. Without regard to the condition of the dentition, the various cases
      could be classified as organic, mixed, or nonorganic in etiology. After dental
      rehabilitation, all patients exhibited an acceleration of weight velocity that
      resulted in weights above the 5th percentile. During the period of observation,
      the weight velocity continued to increase with time, consistent with the "catch
      up" phenomenon of growth that is observed in nutritionally deprived children.

PMID- 9656864
TI  - Root coverage: combined surgical procedures.
AB  - A number of surgical procedures have therapeutic goals to restore the gingival
      tissue to the level of the cementoenamel junction with attachment of soft tissue
      to the previously exposed root surfaces. These procedures are indicated where
      esthetic needs, root sensitivity, or shallow carious lesions involve the root
      surfaces. Surgical innovations over the past decade have enabled the periodontist
      to correct these problems. Case reports of root coverage by combined surgical
      procedures are described and presented. These reports illustrate greater
      predictability and improved esthetics compared to other surgical possibilities.

PMID- 9656865
TI  - Searching for information on the World Wide Web--a guide for dental health
      professionals: Part 2.

PMID- 9656866
TI  - Comparative clinical evaluation of removable partial dentures made from
      impressions with different materials.
AB  - Impressions for removable partial dentures (RPDs) should provide an accurate and
      detailed record of the teeth and soft tissues. Removable partial denture casts
      should be exact replicas of the mouth to ensure that RPD frameworks fit
      accurately and are fully adjusted to oral structures. A comparative clinical
      evaluation was performed on the oral fit of RPDs made from impressions with
      either irreversible hydrocolloid (alginate) or condensation silicone. The
      difference between the two groups was found to be statistically significant.

PMID- 9656867
TI  - Two new schemes for classifying propagating cracks in human tooth structure.
AB  - Currently, the dental profession has no comprehensive classification method or
      scheme to identify the many types of propagating cracks in human tooth structure.
      This article presents two new and practical classification systems that encompass
      numerous types of cracks. The first is the more simplified--the Surface and
      Position Classification System. The second and more comprehensive system is the
      Directional Crack Propagation System.

PMID- 9656868
TI  - Thermology and facial telethermography. Part I: History and technical review.
AB  - This paper is a review of historical trends and technical advances in measurement
      of skin temperature. Most biochemical processes generate heat which must be
      dissipated. Skin is the major route for heat dissipation using blood as the heat
      exchange fluid. Skin temperature is an indicator of aberrations in metabolism,
      hemodynamics or in neuronal thermoregulatory processes. Since most of the heat
      dissipation of skin is by infrared blackbody emission, skin temperature should be
      measured without contact by monitoring the emitted infrared radiation. This has
      been the basis of telethermography. Recent advances in computing technology
      combined with advanced infrared sensor technology has led to the development of
      dynamic area telethermometry (DAT) which promises to be as an important new
      quantitative method to analyse the pathophysiology of thermoregulatory processes.

PMID- 9656869
TI  - Thermology and facial telethermography: Part II. Current and future clinical
      applications in dentistry.
AB  - Selected clinical applications using thermal imaging as an aid in dentistry are
      reviewed. Facial skin temperature can easily be measured in a clinical setting,
      without direct skin contact, by monitoring the emitted infrared radiation. This
      is the basis of static area telethermography (SAT) and dynamic area
      telethermography (DAT). SAT has recently been shown to be of help to the dentist
      in (1) the diagnosis of chronic orofacial pain, (2) as a unique tool in
      assessment of TMJ disorders, (3) as an aid in assessment of inferior alveolar
      nerve deficit, and (4) as a promising research tool. DAT, recently made possible
      by advances in computing technology combined with advanced infrared sensor
      technology, extracts quantitative information about hemodynamic processes from
      hundreds to thousands of digital thermal images of the affected facial areas,
      measured and collected within less than 3 min. DAT has promise of offering a
      better insight into aberrations of the neuronal control of facial skin perfusion
      and aiding our understanding of the correlation between orofacial pain and facial
      thermal abnormalities. This promising new insight may help in the management of
      orofacial pain.

PMID- 9656870
TI  - The influence of radiographic exposure factors on the diagnosis of occlusal
      caries.
AB  - OBJECTIVES: To assess the impact of variations in radiographic density on
      occlusal caries diagnosis and observers' diagnostic strategy. METHODS: Three
      series of radiographs of 60 extracted molars were examined by nine dental
      students and caries diagnosed using a five point confidence-rating scale. Film
      density in each series was varied by varying exposure time: 1 s (high density),
      0.4 s (medium density) and 0.067 s (low density). The 'true' diagnoses were
      obtained by stereomicroscopy. Diagnostic quality was measured with ROC analysis
      as Az. RESULTS: The difference in Az, values between the low and medium density
      series was statistically significant. The sensitivity and the specificity values
      for students' diagnoses in outer third of dentine were 85% and 50% for the high
      density series, 76% and 56% for the medium density series and 42% and 77% for the
      light series. CONCLUSIONS: Occlusal caries was diagnosed best from the darkest
      radiographs. Specificity was higher with light radiographs but sensitivity
      increased with density. Therefore underdiagnosis is more frequent with light
      radiographs, while overdiagnosis occurs more often with dark. The awareness of
      these effects could be an important guideline in adjusting the density of digital
      images.

PMID- 9656871
TI  - The effects of restorative material and location on the detection of simulated
      recurrent caries. A comparison of dental film, direct digital radiography and
      tuned aperture computed tomography.
AB  - OBJECTIVES: To explore the effects of restorative material and lesion location on
      the detection of recurrent caries using intra-oral film, direct digital
      radiography and unprocessed and iteratively restored tuned aperture computed
      tomography (TACT) images. METHODS: An in vitro model with simulated lesions in
      half the surfaces studied was used. Lesions of varying sizes were created at
      either the intersection of the facial or lingual wall and the gingival floor or
      on the gingival floor midway between the facial and lingual walls in the proximal
      boxes of 24 molar teeth with MOD inlay preparations that had been restored with
      amalgam, radiopaque composite or radiolucent composite. RESULTS: Sensitivity and
      specificity values based on restoration were: amalgam: 59 and 87%; radiopaque
      composite: 68 and 78%; radiolucent composite: 36 and 93%; based on lesion
      location, mid-cervical floor region: 51 and 97%; point angle region: 44 and 90%;
      based on imaging modality, film: 40 and 85%; digital: 44 and 76%; unprocessed
      TACT slices: 50 and 87%, iteratively restored TACT images: 83 and 96%.
      Iteratively restored TACT images had the best intra- and inter-reader agreement.
      CONCLUSIONS: The use of restorative materials with a density approximating that
      of enamel is more effective for the detection of recurrent caries. Lesions
      located at the buccal point angle or mid-gingival floor are more easily detected
      than at the lingual point angle region. The sensitivity and specificity of TACT
      and iteratively restored TACT images were superior to those of film and direct
      digital images.

PMID- 9656872
TI  - Panoramic radiographic patterns of the infraorbital canal and anterior superior
      dental plexus.
AB  - OBJECTIVE: To describe and classify the presentations of the infra-orbital
      canal/groove (IOC/G) complex and anterior superior dental plexus (ASDP) on
      panoramic radiographs. METHODS: The frequency of occurrence and variations in
      appearance of the IOC/G were determined on 246 random panoramic radiographs. A
      classification system consisting of Types I, II and III was developed to describe
      the radiographic patterns of the IOC/G. RESULTS: Two hundred radiographs (81.3%)
      demonstrated evidence of the IOG/C. The most frequent appearance of the IOC was
      Type III (44.75%) closely followed by Type I (42%) and Type II (13.25%), with
      only minor differences in prevalence between right and left sides. Sixty one
      percent were bilateral. Radiologic evidence of the ASDP was noted in 29% of
      radiographs demonstrating an IOG/C with 12% of cases being bilateral. Three
      distinct radiographic patterns of the anterior superior dental plexus (ASDP) were
      also observed. CONCLUSION: A classification of the appearance of the IOC/G and
      ASDP on panoramic radiographs has been presented.

PMID- 9656873
TI  - Reduction in size of digital images: does it lead to less detectability or loss
      of diagnostic information? .
AB  - OBJECTIVES: To analyse the effect of reduction in size of digital images on
      diagnostic outcome. METHODS: A series of 100 Visualix III (Gendex Dental Systems,
      Milano, Italy; Dentsply, Des Plaines, IL, USA) images was made of size 10 and 15
      endodontic files in upper and lower (pre)molars. Three forms of image were
      created: (a) the original images, (b) reduced to one-half (containing one-quarter
      of the information of the original, and (c) zoomed-in, half-size images
      (magnification 2:1; original image size but with only one-quarter of the original
      information). Seven radiologists were asked to rate the position of the tip of
      the file, using a five-point confidence scale. ROC data were analysed by means of
      MANOVA statistics. RESULTS: A significant difference was found between the three
      image modalities for both size 10 (P < 0.005), and size 15 (P < 0.021) files.
      CONCLUSIONS: Reduction in size of digital images may cause less detectability as
      well as loss of diagnostic information.

PMID- 9656874
TI  - An evaluation of periapical radiography with a charge-coupled device.
AB  - OBJECTIVES: To compare the standards of periapical radiography with a CCD-image
      receptor with film. METHODS: Three radiography technicians exposed a total of
      fifty teeth from all areas of the jaws using either size 1 or size 2 film and the
      Sidexis (Siemens, Bensheim, Germany) direct digital dental radiography system
      with the appropriate film holders. Image quality was assessed by two dental
      radiologists for nine individual criteria and overall, on a three-point scale.
      RESULTS: There was a significant difference between film and sensor exposures (P
      < 0.014). Six per cent of dental films required retakes compared with 28% with
      the sensor. CONCLUSION: Periapical radiography with a CCD sensor leads to more
      errors and thus more retakes than conventional film.

PMID- 9656875
TI  - Densitometric evaluation of four radiographic processing solutions.
AB  - OBJECTIVE: To determine the performance of different processing solutions using
      an automatic processor for dental radiography. STUDY DESIGN: One brand of dental
      X-ray film (Minimax, Chicago, IL, USA) was developed in an automatic processor
      using four different brands of processing solution: Megasan (MGS, Megasan,
      Ankara, Turkey), (HAC, Ankara, Turkey), Fuji (Fuji Medical, Hacettepe Cedex,
      France) and RP X-Omat (Eastman Kodak, Rochester, NY, USA) at a range of
      temperatures. Performance was evaluated with respect to base plug fog density,
      relative speed and contrast. RESULTS: All solutions produced acceptable base plus
      fog values. MGS produced significantly greater densities (P < 0.05) than the
      other three solutions. Contrast obtained with Kodak and Fuji solutions was less
      than with MGS and HAC. Developing temperature recommended by the manufacturer of
      the processor were found to be higher than that needed to achieve a clinically
      acceptable film. CONCLUSIONS: Depending on the processor and processing solutions
      used, exposure time and processing temperature can be modified while maintaining
      image quality. The cheapest processing solution (MGS) gave the same results as
      the more expensive.

PMID- 9656876
TI  - Comparison of arthroscopy and radiography in patients with temporomandibular
      joint symptoms and generalized arthritis.
AB  - OBJECTIVE: To compare arthroscopy with radiography in patients with
      temporomandibular joint (TMJ) symptoms and generalized joint disease. METHODS:
      Twenty patients with generalized osteoarthritis (GOA) and TMJ symptoms and 21
      patients with rheumatoid arthritis (RA) and TMJ symptoms were examined with
      arthroscopy and radiography (individualized oblique lateral transcranial
      projections and sagittal and frontal tomography). RESULTS: In the GOA group there
      was a significant correlation between pronounced degenerative changes at
      arthroscopy and flattening of the eminence and reduced joint space superiorly and
      posteriorly on radiographs and between moderate to pronounced bone or disk
      remodelling and reduced joint space superiorly and posteriorly. In the RA group
      there was a significant correlation between moderate to pronounced degenerative
      changes at arthroscopy and radiographically extensive erosions in the condyle and
      between moderate to pronounced fibrosis and reduced translation. CONCLUSION:
      Compared with conventional tomography, arthroscopy revealed TMJ pathology earlier
      and more frequently. It may therefore in individual cases be the first choice
      examination, particularly as treatment can be given simultaneously.

PMID- 9656877
TI  - Chondrosarcoma of the maxilla: panoramic radiographic and computed tomographic
      with multiplanar reconstruction findings.
AB  - Chondrosarcomas are extremely rare tumors of which approximately 10% are found in
      the maxillofacial region. In this report, we present the imaging findings of a
      maxillary chondrosarcoma on a panoramic radiograph of the jaws and computed
      tomography with multiplanar reconstructions. We recommend the latter as an
      excellent way to image evolving or suspected lesions of the maxilla, particularly
      for surgical treatment planning.

PMID- 9656878
TI  - Aesthetics for the next millennium.
AB  - The approach of a new millenium provides us, as rhinoplasty surgeons, the
      opportunity to reflect on where we are and where we are going. Aesthetically,
      there are several trends that are evident today. The first is the desire for a
      natural, unoperated appearance to the final rhinoplasty result. Second, is that
      our patient population continues to be more racially diverse; Caucasian normative
      standards of facial analysis are no longer sufficient. What is required is a
      broader understanding of ethnically specific facial features. Third, the standard
      values of facial and nasal analysis are derived from population means. If we
      desire to create beauty, these standards may not be adequate. Beauty is an ill
      defined concept that is obvious to the observer and recognized cross-culturally,
      however, it is difficult to quantify. To consistently achieve beautiful
      rhinoplasty results, we must start with an understanding of what our aesthetic
      ideals should be. This has yet to be satisfactorily defined for all racial groups
      and remains a challenge for the future.

PMID- 9656879
TI  - Anatomy of a rhinoplasty: emphasis on the middle third of the nose.
AB  - The nose is an organ that serves many functions. These functions are intimately
      involved in an organ that occupies a very aesthetically prominent position on the
      face. A thorough knowledge of the anatomy is of the utmost importance for
      surgeons attempting to preserve or improve the functional capability and the
      aesthetic appearance of the nose. Nasal anatomy is extremely complex with a
      myriad of different three-dimensional variances. The middle third of the nose has
      largely been overlooked in its importance. The components of this portions of the
      nose consist of the paired upper lateral cartilages, the dorsal aspect of the
      septum, and the scroll of the upper lateral cartilages upon the lower lateral
      cartilages. This area is of key importance to the nasal valve area and can have a
      major impact on the functional capabilities of the nose. A description of the
      confluence of the flare of the septum to the upper lateral cartilages is
      necessary for an understanding of changes that may occur during rhinoplastic
      operations. A knowledge of the anatomy of the middle third of the nose may
      prevent nasal valve collapse, a pinched appearance of this portion of the nose,
      or an aesthetically unappealing appearance.

PMID- 9656880
TI  - Surgery of the nasal tip.
AB  - One of the most challenging aspects of cosmetic rhinoplasty is nasal tip
      refinement. In efforts to control tip rotation, projection and architecture,
      surgeons face constant tradeoffs between tip position and dorsal reduction. Open
      structure rhinoplasty allows direct visualization of bony-cartilaginous
      deformities, preservation of nasal structural integrity and precise nasal tip
      alteration. The open rhinoplasty technique involves, control of tip projection
      and rotation, reshaping of nasal tip cartilage, minimal resection of the nasal
      dorsum and lower lateral cartilage and preservation or reinforcement of major tip
      supports. The advantage of open structure rhinoplasty includes preservation of
      inherent nasal supporting elements and precise nasal reshaping which are
      essential for aesthetically pleasing and predictable postoperative results.

PMID- 9656881
TI  - Structural grafting in rhinoplasty.
AB  - The need for structural grafting in rhinoplasty arises when the nasal skeletal
      framework is weakened, malpositioned, or both. This review will be limited to
      structural grafting of the cartilaginous nasal skeleton. Current techniques will
      be reviewed and a technique introduced that addresses the common deformity of a
      superiorly rotated and deprojected nasal tip complex while simultaneously
      correcting nasal valve collapse. This technique is referred to as the Dynamic
      Adjustable Rotational Tip (DART) technique. The operative technique of the DART,
      as well as the basic philosophy regarding the tensile nature of the cartilaginous
      nasal skeleton will be described.

PMID- 9656882
TI  - Implants in rhinoplasty.
AB  - A variety of materials have been employed in rhinoplasty for augmentation and
      reconstruction. While autogenous tissue remains the mainstay of nasal implants
      and are the clear choice for structural and augmentation grafting of the nasal
      tip, limited availability and unpredictable resorption or remodeling have made
      homologous and synthetic implants important considerations for dorsal
      augmentation grafting. This section discusses categories of graft materials,
      their physical properties, harvesting and preparation technique, and advantages
      and disadvantages. An algorithm for nasal implants for specific indications in
      support and augmentation is presented.

PMID- 9656883
TI  - Powered instrumentation for dorsal reduction.
AB  - We describe the use of powered instrumentation for precise modification of the
      bony nasal dorsum. Specific modifications were made to design a drill
      specifically for the bony nasal dorsum. This drill has a protective sheath that
      covers all but the active part of the drill, protecting the skin-soft tissue
      envelope, and it also has suction at the resection site. In some cases an
      osteotome is used to reduce the hump and the drill is used to achieve additional
      reduction and to smooth the exposed edges under direct vision. In other cases the
      entire bony hump is reduced using the drill. The nasal dorsum drill offers a
      precise alternative to the rasp. The precision of the drill is highlighted in
      cases in which limited reduction is needed, as in cases of a single or several
      spicules requiring reduction and smoothing after osteotomy, or a single 4 mm
      raised area requiring limited reduction. The design of rasps makes it difficult
      to work on these focal areas without unnecessarily rasping surrounding areas,
      whereas the drill may be used to reduce the entire hump, to smooth the edges
      after osteotomy, or in a more precise and limited fashion when indicated. The
      drill may be less traumatic to the skin-soft tissue envelope because it does not
      rely on the potentially bruising back and forth motion typical of rasping. The
      nasal dorsum drill may decrease the incidence of bony dorsal irregularities after
      rhinoplasty.

PMID- 9656884
TI  - Revision rhinoplasty for monographs in facial plastic surgery contemporary
      rhinoplasty.
AB  - Revision rhinoplasty represents the amalgamation of years of knowledge, judgment,
      technique, communication, self-critique, and patient selection. The surgeon's
      ego, economics, or personality should not persuade or dissuade him or her from
      undertaking revision rhinoplasty. This decision should be made after critical
      evaluation of his/her skills at technical execution, and communicating with the
      patient, as well as the patient's perception and expectations. If any concern
      exists, delay. Re-evaluation and referral become prudent. These patients may
      already be angry. They are obviously dissatisfied with their results and have
      frequently had attempts at revision by the previous surgeon. All these factors
      complicate the psychological aspects of an already difficult task. One other
      realization is the fact that this now becomes your result if it is the revision
      of a colleague's surgery. When comfortable with all of these factors, revision
      rhinoplasty can then be undertaken. The need for revision may be subtle or
      grotesque and can result from a multitude of factors: unrecognized deformities at
      the primary surgery; misunderstood consequences of technique; poor technique;
      unfavorable healing; postsurgical injury; the inevitable need for revision
      surgery in a difficult nose; and poor aesthetic judgment. Revision of one's own
      results is emotionally more difficult, but functionally and technically easier. A
      complete understanding of the primary surgery, access to the initial photographs,
      and a rapport with a patient who is willing to return are all helpful in
      achieving a satisfactory result. In approaching the correction of postoperative
      deformities, it is important to have an understanding of the anatomic abnormality
      as well as the aesthetic deformity. Recognizing the anatomic cause of the
      postsurgical deformity is more relevant to their avoidance and to the maturation
      of the surgeon than to their correction and the desired aesthetic result except
      when functional abnormalities exist and need correction. Ultimately it is the
      deformity that needs to be corrected, and this may or may not require the
      restoration of anatomic normalcy.

PMID- 9656885
TI  - Reconstructive rhinoplasty.
AB  - Reconstructive rhinoplasty for larger nasal defects requires a three-dimensional
      perspective using many of the aesthetic and functional techniques commonly
      employed in rhinoplasty. There are numerous ways of addressing a deficiency of
      the internal lining and each technique is detailed. Structural grafting is
      imperative in order to resist the contracture and collapse of the reconstructive
      nose. These grafts are also used to enhance contour and definition. Resurfacing
      of large cutaneous defects is frequently achieved through the midline forehead
      flap. There are many subtle maneuvers which can significantly impact the final
      aesthetic outcome and these are discussed below. This article highlights the
      three-layered approach to subtotal and total reconstructive rhinoplasty.

PMID- 9656886
TI  - Photo documentation in rhinoplasty.
AB  - Taking good clinical photographs can be simple and fast if a few basic principles
      are followed. An overview of basic photography with an emphasis on germane
      principles is followed by brief discussions of equipment, lighting, positioning,
      and common mistakes. The simplest way to take good photographs is presented. More
      advanced techniques are also discussed. Finally, attention to details in
      examining pre- and postoperative photographs is stressed.

PMID- 9656887
TI  - Substance P-associated increase of intra-articular temperature and pain threshold
      in the arthritic TMJ.
AB  - Neuropeptides are considered mediators and modulators of inflammatory joint
      disease. Substance P (SP) has been proposed as a mediator of pain, and its
      vasoactive properties are well documented. In this study, the presence of SP-like
      immunoreactivity in the synovial fluid was correlated to intra-articular
      temperature (IAT) and pain from the arthritic temporomandibular joint (TMJ) 3 to
      5 weeks after one intra-articular injection of glucocorticosteroids. Eighteen
      TMJs were investigated for IAT and the presence of SP-like immunoreactivity in
      the synovial fluid in 12 patients with systemic inflammatory joint disease. After
      arthrocentesis, the aspirates were analyzed for SP-like immunoreactivity by means
      of competitive radio immunoassay. A visual analogue scale and an algometer
      determining the pressure pain threshold and tolerance level assessed arthritic
      pain and hyperalgesia in the TMJ. Our results indicate that SP-like
      immunoreactivity is associated with IAT and that increased concentrations of
      joint fluid SP-like immunoreactivity correspond to increased pain threshold and
      tolerance and a concomitantly decreased visual analogue scale. These findings
      suggest that SP is implicated in the vascular and nociceptive response of the
      arthritic joint and that SP, possibly assisted by the antinociceptive effect of
      local corticosteroids, has a modulatory role in arthritic pain and hyperalgesia.

PMID- 9656888
TI  - Capsaicin application to the temporomandibular joint alters calcitonin gene
      related peptide levels in the trigeminal ganglion of the rat.
AB  - The aim of this investigation was to determine the temporal effect of an intra
      articular injection of capsaicin to the temporomandibular joint on the levels of
      calcitonin gene-related peptide-like immunoreactivity (CGRP-ir) in the trigeminal
      ganglion of the rat. The temporomandibular joints of 26 adult female rats were
      injected on one side with capsaicin and contralaterally with a control vehicle.
      Another 8 animals served as an untreated control group and received no
      injections. Animals were sacrificed at time intervals of 4 hours, 48 hours, 10
      days, and 21 days following treatment. The trigeminal ganglia were extirpated,
      and CGRP-ir levels were quantified using a radioimmunoassay. Results demonstrated
      that when the capsaicin-treated side and the vehicle-treated side were compared,
      CGRP-ir levels decreased initially at 4 hours and increased at 48 hours. At 10
      days, CGRP-ir levels had again dropped below control levels, followed by an
      increase at 21 days. CGRP-ir levels for the first two time periods investigated,
      which simulate an acute inflammatory state, mimic results observed in studies
      using limb joints, while the other time periods, which represent an intermediate
      and a chronic condition, respectively, suggest a more complex interaction with
      capsaicin-sensitive primary afferents.

PMID- 9656889
TI  - Triazolam improves sleep but fails to alter pain in TMD patients.
AB  - Patients with chronic orofacial pain often report disturbances in sleep, leading
      to the hypothesis that nocturnal motor hyperactivity of the muscles of
      mastication may contribute to the nociceptive process. This hypothesis was tested
      in a controlled study to evaluate the relationship between sleep stages, patient
      self-report of pain in the orofacial region, and nocturnal masticatory muscle
      activity. Twenty subjects participating in a two-period, within-subject,
      crossover study received triazolam or placebo for 4 nights. Sleep, pain, and
      mandibular range of motion were assessed at baseline, following the first period,
      and again following the second period; a 3-day washout period separated the two
      treatments. Subjective report of sleep quality was significantly improved
      following triazolam in comparison to placebo as measured by category scales for
      sleep quality, restfulness, and sleep compared to usual. The amount of time spent
      in stage-2 sleep was also significantly increased by triazolam. No improvement
      was seen in pain as measured by palpation with an algometer, in scales for
      sensory intensity and the affective component of pain, or in daily pain diaries.
      Mean facial muscle electromyographic activity for 30-second epochs averaged over
      the entire period of sleep did not reveal any differences in muscle activity
      across the three conditions. These data indicate that improvements in sleep
      quality and alterations in sleep architecture do not affect nocturnal facial
      muscle activity or subsequent pain report in temporomandibular patients, thereby
      failing to support the hypothesized relationship between sleep disturbances and
      chronic orofacial pain.

PMID- 9656890
TI  - Physical therapy for patients with TMD: a descriptive study of treatment,
      disability, and health status.
AB  - The purposes of this study were to compare disabilities and health status
      associated with temporomandibular disorders (TMD) to other musculoskeletal
      disorders, to describe the types of physical therapy administered to patients
      with TMD, and to evaluate health-related quality of life (HRQOL) as an index of
      clinical change following physical therapy treatment. Outcomes for 56 patients
      (mean age 40 years, SD 13 years; 89% female) were evaluated from a large database
      generated by the Focus on Therapeutic Outcomes network. A generic assessment of
      HRQOL--the Medical Outcomes Study (MOS) 17--was used to evaluate the physical and
      mental aspects of disability associated with TMD, and the results were compared
      descriptively to three groups of patients with different cervical pain syndromes.
      The results showed that patients with TMD had limitations in social function,
      emotional well-being, and energy level similar to patients with cervical
      disorders. Physical function (i.e., walking, carrying loads, or lifting),
      however, was much more limited in cervical disorder patients and bodily pain
      interfered more with daily work. Large positive effect sizes (> 0.80) in the
      areas of social function and bodily pain indicated clinical improvement for
      patients with TMD at the completion of physical therapy. The results suggest that
      the MOS-17 may be useful as one measure of clinical change for patients with TMD
      who receive physical therapy.

PMID- 9656891
TI  - Somatic complaints, psychologic distress, and treatment outcome in two groups of
      TMD patients, one previously subjected to whiplash injury.
AB  - The aim of this study was to compare somatic complaints and psychologic distress
      in a group of whiplash patients with temporomandibular disorders (TMD) and a
      group of patients with TMD only, and to assess the outcome after conservative TMD
      treatment consisting of counseling, muscle exercises, and a stabilization splint.
      Each group consisted of 16 patients (12 women and 4 men) with a mean age of 42
      years. The duration of the symptoms was from 1 to 3 years. In addition to a
      functional clinical examination and a recording of headache frequency and
      intensity, the patients answered three questionnaires: a Somatic Complaints
      Questionnaire (SCQ); the trait portion of Spielberger's State-Trait Anxiety
      Inventory; and the Symptom Checklist-90-Revised (SCL-90-R). The whiplash patients
      had higher scores than the TMD patients on the SCQ muscle score and on the
      following subscores of SCL-90-R: obsession, somatization, depression, and
      anger/hostility. The treatment outcome as assessed by the change of self-reported
      frequency of headache, number of tender muscles upon palpation, and change of
      values on a visual analogue scale for headache intensity showed that the whiplash
      patients obtained only a decrease in the proportion of tender muscles, while
      those in the TMD only group showed improvement on all treatment criteria.

PMID- 9656892
TI  - Effect of parafunctional clenching on TMD pain.
AB  - Parafunctional activities are assumed to play an important role in
      temporomandibular disorders (TMD), but experimental data in support of this
      hypothesis are lacking. This study examined the role of parafunctional clenching
      on various measures of TMD pain. Five subjects participated in daily 17-minute
      electromyogram biofeedback training sessions structured in three phases. Subjects
      were instructed to maintain temporalis and masseter muscle activity below 2
      microV in the first (decrease) phase of training (10 sessions), above 10 microV
      in the second (increase) phase (1 to 8 sessions), and below 2 microV in the third
      (decrease) phase (10 to 15 sessions). Preliminary screening examinations showed
      that none of the subjects had TMD. Two subjects reported intolerable pain during
      increase training, and both were diagnosed with a TMD during this phase. No
      subject was diagnosed with TMD pain during either decrease training phase. The
      authors conclude that chronic, low-level parafunctional clenching may be a factor
      in the cause of TMD pain.

PMID- 9656893
TI  - Evaluation of shear stress of the human temporomandibular joint disc.
AB  - The aim of this study was to determine the shear stress of the human postmortem
      temporomandibular joint (TMJ) disc. Correlation of shear stress with age or with
      the region of the disc was determined. Nine discs were removed unilaterally from
      postmortem humans, ages 36 to 76 years. Discs were sectioned into lateral
      (eight), central (eight), and medial (eight) specimens. Each specimen was
      attached by cyanoacrylate adhesive to a servohydraulic test system apparatus
      within 48 hours of retrieval. Shear properties were measured under quasistatic
      conditions with a linear increase of displacement until the specimen failed to
      maintain maximum resistance to the applied force. The shear moduli were analyzed
      by means of the Wilcoxon's signed ranks test. The results showed that values of
      shear moduli on peripheral portions (lateral and medial) were significantly
      higher than on central portions (P = 0.0013). The correlation between the shear
      moduli of TMJ discs and age showed a regression slope for shear moduli of -0.326
      + 0.031 x age (r = 0.769; P < 0.01). Peripheral portions (lateral and medial)
      have a higher shear moduli and are stiffer than the central portions of discs and
      shear moduli or stiffness of TMJ discs increase with age.

PMID- 9656894
TI  - Muscle pain modulates mastication: an experimental study in humans.
AB  - In this study, pain was induced in the masseter muscle by tonic infusion of
      hypertonic saline (5%) for up to 800 seconds in 12 healthy men. Subjects
      continuously scored the pain intensity on a 10-cm visual analogue scale.
      Mastication ipsilateral and contralateral to the infusion side was quantitatively
      assessed with the use of jaw-tracking and electromyograph recordings of jaw
      closing muscles before, during, and after periods of constant muscle pain
      intensity. The maximum voluntary occlusal force (MVOF) during short static
      contractions also was monitored. Jaw movements and electromyographic data were
      divided into single masticatory cycles and analyzed on a cycle-by-cycle basis to
      account for intercycle variability. In all subjects, tonic infusion caused a deep
      localized pain at a clinically relevant intensity (mean VAS +/- SE, 4.6 +/- .3
      cm). MVOF was significantly affected by muscle pain (P < .0005), with
      significantly lower MVOF during pain compared to prepain and postpain (P < .05).
      In a significant number of masticatory cycles, the averaged electromyograph
      activity of all jaw-closing muscles during their agonist function was decreased
      for both ipsilateral and contralateral painful mastication (P < .05). These
      electromyographic changes are probably a reflection of the natural bilateral
      recruitment pattern of jaw-closing muscles during mastication. Significant
      changes in jaw movements during painful mastication could not be detected with
      the present jaw-tracking device, but further studies with more accurate and
      sensitive devices are needed.

PMID- 9656895
TI  - The reproducibility of muscle and joint tenderness detection methods and maximum
      mandibular movement measurement for the temporomandibular system.
AB  - The purpose of this study was (1) to evaluate the reproducibility of two
      masticatory muscle and joint tenderness detection methods; (2) to evaluate the
      reproducibility of maximum mandibular movement measurements; and (3) to
      investigate factors influencing examiner agreement. The tenderness assessment
      procedures involved application of a standard pressure for 2 seconds over four
      anatomically defined masticatory muscle sites, one control forehead site, and two
      temporomandibular joint sites on each side of the face. One technique utilized a
      pressure algometer (PAP), while the other technique required that a trained
      examiner apply pressure with the index fingertip (FPP). Seventy-two subjects (36
      patients and 36 controls) were evaluated in a single-blind study design. Control
      subjects were matched for age, gender, and race with temporomandibular disorder
      subjects. Each subject was examined twice with each of the described methods in a
      randomized, fully balanced sequence by calibrated examiners. Tenderness levels
      were determined by the subject via self-report of pain upon pressure using a
      standard set of verbal descriptors. Maximum pain-free, active, and passive
      opening, and maximum active right and left lateral movements were measured using
      a millimeter ruler. Intraclass correlation coefficients (ICC) for the tenderness
      assessment methods ranged from 0.220 to 0.739 for the FPP method and from 0.391
      to 0.880 for the PAP method. ICCs for mandibular movement measurement were much
      less variable, ranging from 0.59 to 0.68 for lateral movement and from 0.78 to
      0.93 for opening movement. These results indicate good to excellent agreement
      between calibrated examiners for mandibular movement measurement and for
      tenderness assessment methods at two masseter (i.e., superficial and deep) and
      the anterior temporalis sites. Only fair agreement was found for the middle
      temporalis and lateral TMJ capsule sites using these methods.

PMID- 9656896
TI  - Pain threshold responses to two different modes of sensory stimulation in
      patients with orofacial muscular pain: psychologic considerations.
AB  - This study focuses on the influence of trait anxiety and mood variables on
      changes in tooth pain threshold following two similar methods of somatic afferent
      stimulation, one familiar (manual acupuncture) and one unfamiliar (low-frequency
      transcutaneous electrical nerve stimulation [low-TENS]). Twenty-one acupuncture
      responders, treated for long-lasting orofacial muscular pain but naive to low
      TENS, were selected for the study. In an experimental session, acupuncture and
      low-TENS were randomly given during two periods separated by a rest interval.
      Tooth pain thresholds (PT) were measured before and after stimulation with a
      computerized electrical pulp tester. Trait anxiety and depression were assessed
      with psychometric forms before the experimental session in all patients, whereas
      momentary mood was assessed in 10 randomly selected patients with visual analogue
      scales during and after the two types of stimulation. Following acupuncture, the
      group average PT increased significantly, whereas no significant change was
      observed following low-TENS. Higher scores on trait anxiety correlated
      significantly with a low PT increase following low-TENS, and higher ratings of
      stress correlated significantly with a low PT increase following acupuncture.
      This indicates that the magnitude of analgesia induced by these methods may be
      modified by psychologic factors like anxiety and stress.

PMID- 9656897
TI  - Comparison of clinical and psychologic features of fibromyalgia and masticatory
      myofascial pain.
AB  - The aim of this study was to investigate common symptoms and divergent features
      in fibromyalgia (FS) and masticatory myofascial pain (MFP) in patients affected
      by craniomandibular disorders. Twenty-three women with MFP and 23 women with FS
      were studied. All patients were examined by a dentist and by a rheumatologist.
      Craniomandibular disorders were assessed with a subjective symptoms
      questionnaire, detailed history interview, joint function examination, and manual
      palpation of masticatory and cervical muscles. The Middlesex Hospital
      Questionnaire was used to obtain personality profiles of the patients. The
      craniomandibular disorders questionnaire revealed various similarities in the two
      groups, the most striking of which were pain during mandibular function,
      articular noises, and headache. Both groups had muscle pain upon palpation; the
      mean scores (on a 0 to 4 scale) did not differ significantly between the two
      groups and ranged between 1.39 (SD 1.2) and 2.86 (SD 0.75). The mean value of
      active mouth opening was 40.9 mm (SD 9.1) in MFP patients and 44.6 mm (SD 7.2) in
      FS patients, while the mean value of passive opening was 49.6 mm (SD 6.0) in MFP
      patients and 49.8 mm (SD 3.5) in FS patients. These values did not differ
      significantly between the two groups, but did differ from the normal population,
      similar to the trend of the psychologic profile. The authors conclude that the
      physician should be alert to the need to conduct interdisciplinary evaluations in
      the diagnosis and management of FS and of MFP.

PMID- 9656898
TI  - Temporomandibular disorders in children and adolescents: reliability of a
      questionnaire, clinical examination, and diagnosis.
AB  - Recently developed Research Diagnostic Criteria for Temporomandibular Disorders
      (RDC/TMD) have been shown to be reliable for diagnosing and assessing TMD in U.S.
      and Swedish adult populations; however, few studies have focused on clinical
      examination methods and diagnostic criteria for use with children and
      adolescents. The present study used a sample of 50 Swedish children and
      adolescents, aged 12 to 18 years, to evaluate usefulness and reliability of
      existing and specially developed measures and methods for assessing and
      diagnosing TMD in youth. Subjects underwent repeated clinical exams by two
      calibrated examiners to assess signs and symptoms per the RDC/TMD, and they
      responded to a specially developed self-administered questionnaire that addressed
      location and frequency of TMD-related pain and symptoms, jaw function, effect of
      pain on daily activities, and use of pain medications. Interexaminer and
      intraexaminer reliability was assessed for clinical examination, questionnaire
      items, and diagnosis. Reliability values ranged from acceptable to excellent for
      the RDC/TMD clinical exam and questionnaire, and from good to excellent
      reliability for measuring virtually all modified clinical parameters of TMD
      assessed in these young patients.

PMID- 9656899
TI  - Pain preceding recurrent head and neck cancer.
AB  - Over a 7-year period, 12 patients experienced recurrence of primary head and neck
      cancers preceded by severe orofacial pain. Pain began within 6 months following
      treatment in 10 of 12 patients and was progressive in 11 of 12 patients. Six
      patients died from recurrence, five within 2 years following onset of pain. No
      clear indication of malignant disease was evident despite clinical examination,
      plain radiography, magnetic resonance imaging, and computed tomography. Pain was
      often mistaken for denture irritation. Frequently, no area of irritation was
      apparent.

PMID- 9656900
TI  - Treatment-seeking patterns of facial pain patients: many possibilities, limited
      satisfaction.
AB  - Knowledge about the different kinds of treatment provided to patients with
      nonmalignant musculoskeletal facial pain is limited. The present study was based
      on 206 consecutive patients who were referred to a university-based tertiary care
      clinic for the diagnosis and management of persistent facial pain. Its purpose
      was to get information about the number and specialty of providers consulted by
      patients prior to their referral, and to follow the underlying treatment-seeking
      patterns. The results showed that on average 4.88 providers from 44 different
      categories were consulted. A general dentist or a dental specialist was seen by
      about 70% of patients. For patients whose first provider was a dentist, the most
      likely subsequent provider was another dentist. Conversely, if the first provider
      was a physician, chances were greater that the subsequent provider was a
      physician rather than a dentist. Among the nondental therapies patients received,
      physical therapy was chosen most frequently (42.2%). More than 60% of patients
      had at least one nondental treatment; however, the majority of these patients
      experienced two or more different types of such therapy (e.g., chiropractic,
      osteopathic, relaxation training). Patients' satisfaction with care and treatment
      was moderate, since only 18.5% of the patients were very satisfied, while 27.7%
      were dissatisfied or very dissatisfied. The present findings, which corroborate a
      recent study from the Kansas City, Missouri, region, indicate that patients with
      persistent facial pain see a large number of different providers, and that
      nonmedical/nondental treatment approaches are common. The moderate satisfaction
      experienced with any of the therapies points out that much needs to be done
      before this patient population is served satisfactorily.

PMID- 9656901
TI  - TMD treatment need in relation to age, gender, stress, and diagnostic subgroup.
AB  - Associations between treatment need for temporomandibular disorders (TMD) and
      age, gender, stress, and diagnostic subgroup were analyzed in an adult Finnish
      population sample of 506 subjects. When analyzed separately, the association
      between TMD treatment need and all the studied factors was statistically
      significant. This finding is in accordance with earlier results. When the studied
      factors were included into an explanatory model, however, the picture changed.
      The logistic regression analysis revealed that diagnostic subgroup was the
      strongest predictor for the TMD treatment need. Total stress score significantly
      added to the explanatory power of the model, but age and gender did not. The
      commonplace observation that women show more signs and symptoms of TMD seems to
      be explainable by their higher stress scores and by the type of symptoms.

PMID- 9656902
TI  - The long-term effect of occlusal therapy on self-administered treatment outcomes
      of TMD.
AB  - Because of a lack of substantial scientific data, the efficacy of occlusal
      therapy for the management of temporomandibular disorders (TMD) is still
      controversial. Of a total of 1405 consecutive TMD patients examined over the last
      10 years, 369 (26.3%) were determined to have completed treatment at least 1 year
      before the present survey. A sample questionnaire was mailed to each patient in
      this sample population. The questionnaire failed to reach 46 patients; of the 323
      patients who received the questionnaire, 260 (80.5%) responded. The mean duration
      of time between their last visit and this survey was 3.7 years. The questionnaire
      elicited information on treatment outcomes, present treatment needs, and current
      signs and symptoms. Participants were divided into two treatment groups: (a)
      those who underwent some occlusal therapies (Phase II) following successful
      reversible therapies (Phase I) (20 men and 114 women); and (b) those who
      underwent reversible therapy only (33 men and 93 women). Participants were
      further differentially diagnosed into five diagnostic subgroups of TMD, based on
      the clinical examination at the initial visit, tomography, and, for some
      patients, magnetic resonance imaging. The subgroups included myalgia, arthralgia,
      anterior disc displacement with an without reduction, and
      osteoarthritis/osteoarthrosis. Only 12.3% of the total population surveyed
      reported lack of improvement to an acceptable level and further need for
      treatment. The remaining patients reported satisfactory results in the reduction
      of TMD symptomatology and no further need for treatment, because their symptoms
      had either disappeared or improved to an acceptable level. Regardless of
      treatment groups and diagnostic subgroups, the current subjective signs and
      symptoms were negligible in most patients, and mean mouth openings were in the
      normal range. No particular diagnostic subgroups seemed to have significantly
      better outcome following Phase II occlusal therapy. These results suggest that
      the majority of TMD signs and symptoms improve to an acceptable level with only
      reversible therapy, and the long-term value of additional occlusal therapy
      following reversible therapy is minimal. Therefore, permanent occlusion-changing
      therapies apparently are not generally needed to maintain TMD symptom reduction
      over time.

PMID- 9656903
TI  - Pain descriptors characteristic of persistent facial pain.
AB  - The McGill Pain Questionnaire is an instrument that is widely used to assess the
      multidimensional experience of pain. Although it was introduced more than 20
      years ago, limited information is available about its use in patients suffering
      from persistent facial pain. The aim of this study was to investigate the
      response patterns of persistent facial pain patients to the McGill Pain
      Questionnaire, to correlate these patterns with patients' beliefs about the
      seriousness of the condition, and to compare the findings with data reported from
      other painful conditions. The study sample consisted of 200 consecutive female
      patients referred to a tertiary care facial pain clinic. The Pain Rating Index
      scores of the McGill Pain Questionnaire subscales and the total number of words
      chosen by these patients closely matched the summary scores reported by Wilkie et
      al, who pooled data from seven pain conditions (cancer, chronic back, mixed
      chronic, acute/postoperative, labor/gynecological, dental, and experimentally
      induced) in their meta-analysis. On the other hand, when the data collected in
      this study were compared with those from specific clinical subsets, such as
      cancer patients, chronic back pain patients, or dental patients, differences in
      McGill Pain Questionnaire scores could be identified. Differences were also found
      in the choice of specific pain descriptors. More than 20% of the facial pain
      patients selected "radiating" and "pressing"; this was not the case for those
      suffering from other pain conditions. Facial pain patients who felt that their
      condition was more serious or different from what the treatment providers had
      told them had a greater likelihood of choosing specific word categories of the
      McGill Pain Questionnaire.

PMID- 9656904
TI  - The effects of tongue position on mandibular muscle activity.
AB  - The purpose of this study was to determine the relationship between tongue
      position and mandibular muscle activity. Thirty-three subjects (28 women) between
      the ages of 18 and 34 years (mean = 22.1 years) with no prior injury to or pain
      in the jaw, mouth, or tongue participated in the study. Subjects were asked to
      rest quietly while baseline electromyographic recordings were made from the
      temporalis, masseter, and suprahyoid muscle regions. Afterwards, subjects were
      randomly assigned to conditions requiring them to position the tongue either
      "against the anterior palate" or "on the floor of the mouth, making sure the tip
      does not press against any part of the mouth." The results indicated that right
      temporalis activity was higher when the tongue was positioned against the roof of
      the mouth than when it was either at baseline or resting on the floor of the
      mouth (P < .03). A similar pattern of results was observed for the suprahyoid
      muscle group (P < .01). There were no significant differences in masseter muscle
      activity as a function of tongue position (Ps > .20). These findings suggest
      caution in labeling the "rest" position of the tongue and indicate that further
      study of the relationship between tongue position and orofacial pains in needed.

PMID- 9656905
TI  - Waking and sleeping temporalis EMG levels in tension-type headache patients.
AB  - Temporalis muscle activity in tension-type headache subjects (n = 36) and in
      matched nonheadache controls (n = 36) was evaluated in this study. Subjects'
      cumulative temporalis muscle activity was recorded every 30 minutes for 3 days
      and night using an electromyographic recorder. Analysis of variance showed that
      neither the waking nor the sleeping overall muscle activity levels for these two
      groups were statistically different. When the waking EMG data were dichotomized
      into function and nonfunction activities, a significant difference was found
      between groups during jaw function (i.e., chewing and talking). These data
      suggest that headache subjects are using their temporalis muscles with less
      efficiency than nonheadache subjects during function. This elevated EMG is more
      likely a consequence of pain (via protective splinting or guarding) rather than a
      cause in tension-type headache sufferers.

PMID- 9656906
TI  - The efficacy of dry needling and procaine in the treatment of myofascial pain in
      the jaw muscles.
AB  - In patients with myofascial pain, painful trigger points are often treated using
      dry needling and local anesthetic injections. However, the therapeutic effect of
      these treatments has been poorly quantified, and the mechanism underlying the
      effect is poorly understood. In a randomized, double-blind, double-placebo
      clinical trial, a pressure algometer was used to measure pain-pressure thresholds
      in the masseter and temporalis muscles of 30 subjects aged 23 to 53 years with
      myofascial pain in the jaws, before and after a series of dry needling
      treatments, local anesthetic injections, and simulated dry needling and local
      anesthetic treatments (treatment group A: Procaine + simulated dry needling;
      treatment group B: dry needling + simulated local anesthetic; control group C:
      simulated local anesthetic + simulated dry needling). Subjects rated pain
      intensity and unpleasantness using visual analogue scales, and the data were
      analyzed using analysis of variance. Pain pressure thresholds increased slightly
      after treatment, irrespective of the treatment modality. Pain intensity and
      unpleasantness scores decreased significantly at the end of treatment in all
      groups. There were no statistically significant between-group differences in pain
      pressure thresholds and visual analogue scale scores at the end of treatment. The
      findings suggest that the general improvement in pain symptoms was the result of
      nonspecific, placebo-related factors rather than a true treatment effect. Thus,
      the therapeutic value of dry needling and Procaine in the management of
      myofascial pain in the jaw muscles is questionable.

PMID- 9656907
TI  - The natural course of nonreducing disc displacement of the TMJ: relationship of
      clinical findings at initial visit to outcome after 12 months without treatment.
AB  - The natural course of untreated nonreducing disc displacement of the
      temporomandibular joint was evaluated in 52 patients (total of 57 affected
      temporomandibular joints). The association between the clinical findings at the
      initial visit and the outcome at 12 months for the age, range of motion for
      maximum mouth opening, intercuspal-occlusal relationship, morphology of the
      mandibular fossa and the articular eminence, and the locking duration was
      evaluated. Good resolution was seen in 59.6% of the patients. The patients with
      good resolution were significantly younger than those with poor resolution (P <
      .05, two-tailed t test); however, there were no differences in any other factors
      between the patients with good resolution and those with poor resolution. Natural
      resolution of clinical signs and symptoms was suggested for the majority of
      patients with nonreducing disc displacement of the TMJ, and a younger age at the
      initial visit appears to be a positive factor in the prognosis.

PMID- 9656908
TI  - Adolescent TMJ tomography and magnetic resonance imaging: a comparative analysis.
AB  - The predictive value of radiographic tomography was assessed using magnetic
      resonance imaging as a definitive test of TMJ soft-tissue status in a
      predominantly asymptomatic adolescent sample. Eighty-two TMJs in 41 subjects
      (mean age = 12.5 years, range = 10 to 17 years) were independently evaluated
      using axially corrected tomography and magnetic resonance imaging. Tests of
      comparison and correlation were performed. Correspondence of tomographic
      classification to magnetic resonance imaging classification of nondisplacement
      (55%), reducing internal derangement (35%), or nonreducing internal derangement
      (10%) showed a significant relationship (P < .05). Tomography as a diagnostic
      test of abnormal disc position had a sensitivity of 0.43, a specificity of 0.80,
      a positive predictive value of 0.64, and a negative predictive value of 0.63.
      Tomography is inappropriate as a diagnostic test for TMJ internal derangement.

PMID- 9656909
TI  - Bilateral condylar movement patterns in adult subjects.
AB  - The purpose of this study was to determine if there was a difference between the
      temporomandibular condylar movement patterns of a symptomatic adult population
      and those of an asymptomatic adult population. Thirty-five volunteers who were
      not seeking treatment for TMD underwent two different assessments for TMD signs
      and symptoms: (1) a self-administered questionnaire and (2) a clinical
      examination. Based on the information obtained from the questionnaires, subjects
      were divided into "reported-symptomatic" and "reported-asymptomatic" groups.
      Based on the investigator's clinically evaluation of the same subjects, subjects
      were divided into "clinically symptomatic" and "clinically asymptomatic" groups.
      To compare condylar movement patterns, both groups of subjects then had their
      mandibular border condylar movements measured bilaterally using a sagittal
      recording device during maximum opening, maximum protrusion, and maximum left and
      right excursion movements. The patterns were separated into two broad groups,
      "symmetric" and "asymmetric." Symmetric gliding movements were defined as
      uninterrupted bilaterally mirror-like patterns of each condyle with a difference
      between left and right total length excursion not exceeding 2 mm during opening
      in the sagittal plane or horizontal plane. Our results show that 63% of the
      subjects who reported clinically asymptomatic for TMD demonstrated asymmetric
      condylar movements. However, 100% of the patients (n = 5) who reported clinically
      symptomatic for TMD exhibited asymmetric condylar movements. This finding
      suggests that, while a very high percentage of TMD subjects will have asymmetric
      condylar movements, condylar movements alone are not necessarily diagnostic of
      TMD, and the sagittal recording device may alert the clinician to abnormal
      movements.

PMID- 9656910
TI  - A comparison of TMD patients with or without prior motor vehicle accident
      involvement: treatment and outcomes.
AB  - The influence of previous trauma in the management of patients with
      temporomandibular disorders (TMD) is controversial. The objectives of this study
      were to compare treatment regimens and outcomes in motor vehicle accident trauma
      related versus nontrauma-related TMD patients. Files of 50 trauma and 50 matched
      nontrauma TMD patients were reviewed. Information concerning treatment received,
      progress of symptoms with treatment, and findings from the final examination were
      recorded. As a whole group, posttraumatic TMD patients tended to receive more
      types of treatment (P < .0001), have more medications prescribed (including
      analgesics, P < .001; nonsteroidal anti-inflammatory drugs, P = .001; muscle
      relaxants, P = .001; and tricyclic antidepressants, P < .001), have more oral
      medicine clinic visits (P = .07) over a longer period of time (P = .06), and have
      a poorer treatment outcome (P < .001) as compared to the nontrauma group. When
      the patients were separated into TMD diagnostic classification subsets, only some
      of these differences between trauma and nontrauma patients were seen, but the
      subset group sizes were small and only a few of the groups could be compared.
      There did not seem to be a significant effect from settling insurance claims
      prior to the last clinic visit. Trauma may be an important prognostic factor in
      the management of some TMD patients.

PMID- 9656911
TI  - Topical clonidine for orofacial pain: a pilot study.
AB  - An open-label trial of clonidine, an alpha 2-adrenergic agonist, was prescribed
      for patients with a clinical diagnosis of oral neuropathic pain or neuralgia
      involving the oral cavity. Clonidine (0.2 mg/g) was prepared in a cream base and
      applied four times daily to the site of pain. Seventeen patients were assessed:
      10 were diagnosed with neuropathic pain, and 7 with neuralgia. Two of the 17
      patients had complaints overlapping both neuropathic and neuralgic pain. In the
      patients with neuropathic pain, an overall mean reduction in severity of burning
      of 36% (on a 10-point visual analogue scale) was reported. Half of these patients
      reported clinical improvement; however, no patients reported complete resolution
      of symptoms. Of the patients with characteristics of neuralgia, 57% improved; and
      in those who reported improvement, a mean reduction of approximately 54% was
      reported. In the 4 patients with neuralgia who responded, a 94% reduction in pain
      was reported, with complete resolution of pain in 2 patients. This open-label
      clinical trial suggests that topical clonidine may be effective in the management
      of some patients with oral neuralgia-like pain, but may have a more limited
      effect in those patients with oral neuropathic pain. Besides type of pain, no
      other variables predicted which of the patients would achieve pain reduction with
      topical clonidine. Although confirmation of clinical efficacy requires double
      blind clinical studies, this initial trial suggests that further study is
      warranted.

PMID- 9656912
TI  - Effect of systemic versus topical nonsteroidal anti-inflammatory drugs on
      postexercise jaw-muscle soreness: a placebo-controlled study.
AB  - Certain types of jaw-muscle pain may be managed with pharmacologic treatment.
      This study evaluated the effect of topical and systemic nonsteroidal anti
      inflammatory drugs on acute postexercise jaw-muscle soreness. Ten men without
      temporomandibular disorders performed six 5-minute bouts of submaximal eccentric
      jaw exercise. The outcome variables were pressure pain thresholds and pain
      tolerance thresholds at the masseter muscles, and maximum voluntary occlusal
      force. Surface electromyography from the masseter muscles was used to assess the
      development of muscle fatigue during the exercise period. Three treatment
      modalities were tested in a placebo-controlled, double-blind approach: (A)
      placebo gel and placebo tablets; (B) nonsteroidal anti-inflammatory drug gel (2
      g, 5% ibuprofen) and placebo tablets; and (C) placebo gel and nonsteroidal anti
      inflammatory drug tablets (400 mg ibuprofen). The subjects used their medication
      3 times a day for 3 days in the postexercise period. In the exercise period, the
      mean power frequency of the electromyography signal, pressure pain threshold,
      pain tolerance threshold, and maximum voluntary occlusal force decreased
      significantly (analysis of variance, P < .01). In the postexercise period, the
      effect of treatment on pressure pain thresholds was significant (F[2,9] = 4.41, P
      = .02). On day 3, treatment with topical nonsteroidal anti-inflammatory drugs was
      associated with significantly higher pressure pain thresholds as compared to
      treatment with systemic nonsteroidal anti-inflammatory drugs (P < .05) and
      placebo (P < .05). Treatment effects on pain tolerance thresholds and on maximum
      voluntary occlusal force were nonsignificant. The results demonstrated that
      repeated eccentric jaw exercise caused muscle fatigue and low levels of
      postexercise pain and soreness. Topical nonsteroidal anti-inflammatory drugs seem
      to have some advantages over systemic nonsteroidal anti-inflammatory drugs for
      management of exercise-induced jaw-muscle pain.

PMID- 9656914
TI  - Strategically replenishing your capital assets.

PMID- 9656913
TI  - Guarding against the decline of dental practice value.

PMID- 9656915
TI  - Advantages and procedures using air abrasion.

PMID- 9656917
TI  - A new paradigm for a new age.

PMID- 9656916
TI  - Air abrasions and caries detection dyes. The new standard of care.

PMID- 9656918
TI  - The Internet: so you want to get connected.

PMID- 9656919
TI  - Writing an expert report.
AB  - Anna was flustered. It had been three months since her patient had asked for a
      report about the accident. Anna had been procrastinating and now her patient was
      threatening to report her to the college if it wasn't ready by Monday. As Anna
      sat down at the computer, she did not know where to begin. Should she outline the
      history of the accident given by her patient or would any discrepancies between
      this history and her patient's version cause problems at the hearing? How much
      detail should be included about the assessment and the treatment? Anna felt
      uncomfortable expressing an opinion about her patient's prognosis, particularly
      since she had not assessed the patient in six months. Anna also wondered how much
      to charge for the report and whether she could insist upon payment before
      releasing the report. How did she ever get herself into this situation?

PMID- 9656920
TI  - Early fracture resistance of amalgapin-retained complex amalgam restorations.
AB  - Amalgapins are susceptible to early fracture during matrix removal and carving.
      The purpose of this study was to examine the early fracture resistance of
      amalgapin-retained restorations using a spherical amalgam alloy, an admixed
      amalgam alloy, a combination of admixed alloy over the spherical alloy, and a
      recently introduced modified spherical amalgam alloy. Four amalgapin channels
      with a diameter of 1.4 mm and depth of 2 mm were prepared in cylinders of Macor,
      a machinable ceramic material. The amalgapins were hand condensed, and the bulk
      of the restoration was mechanically condensed. In the group using the combination
      of alloys, 800 mg of spherical alloy was condensed into the amalgapins and over
      the floor of the preparation. The admixed alloy was then condensed over the
      spherical alloy to build up the bulk of the restoration. Using an Instron
      Universal Testing Machine, the restorations were tested to shear failure at an
      average of 15.8 +/- 1.3 minutes after the initiation of trituration of the
      amalgam alloy. A metal ring was placed around the restoration and pulled 90
      degrees to the long axis to simulate matrix band removal. Data were analyzed
      using Kruskal-Wallis procedures. The fracture resistance of the spherical alloy
      group and the spherical/admixed group were significantly higher than admixed or
      Tytin FC. All fractures occurred in amalgam at the entrance to the amalgapin
      channel. The combination of spherical and admixed amalgam alloys in a restoration
      may reduce the potential for early dislodgment while allowing additional time for
      carving.

PMID- 9656921
TI  - Effects of lining materials on shear bond strength of amalgam and gallium alloy
      restorations.
AB  - In this in vitro study, where alloys were condensed into unset paste lining
      materials, shear bond strengths were significantly greater than with the unlined
      controls. The use of varnish or Paama 2 linings did not significantly increase
      the shear bond strength of amalgam or gallium alloy restorations. The use of
      Vitrabond, Vitremer, or Resinomer liners significantly increased the shear bond
      strength compared to unlined restorations. Permite C restorations lined with
      Resinomer all showed cohesive failure within the mixed alloy/ liner. Of the
      unlined restorations, Permite C had significantly higher shear bond strength than
      Lojic Plus. The experimental method used in the present study proved to be
      suitable for quantitative comparison of the shear bond strength of different
      dental materials.

PMID- 9656922
TI  - Shear bond strength of immediately repaired light-cured composite resin
      restorations.
AB  - The goal of this study was to examine the extent to which the state of the
      surface of newly placed restorations made of one of two commercial formulations
      of composite resin (Pertac-Hybrid and Z-100) affects the interfacial bond
      strength when such restorations are immediately repaired with the same resin.
      Three groups of specimens for each material were prepared: one group in which
      there was an air-inhibited film on the surface of the initial layer of the
      restoration, another in which that film was prevented from being formed, and a
      third in which that surface was abraded prior to placement of the repair layer.
      All specimens were stored for 6 weeks in water at 23 degrees C before being
      loaded to fracture in shear at a rate of 5 mm/min. The shear bond strength
      results were treated using the three-parameter Weibull equation and a clearly
      defined index of performance (I), which is a measure of both the magnitude and
      variability of the shear bond strength. It was found that, for two states of the
      surface of the initial layer, I for Pertac-Hybrid specimens is about the same as
      that for Z-100 specimens. For specimens made of either material, there was a
      demonstrable difference in I between specimens with or without an air-inhibited
      film on the initial layer, while abrading the surface of that layer severely
      degraded I.

PMID- 9656923
TI  - Using double-poured alginate impressions to fabricate bleaching trays.
AB  - Esthetic and diagnostic treatment often requires two casts of one arch, one for
      baseline and one for alterations (diagnostic wax-up, bleaching tray, occlusal
      analysis). The purpose of this study was to compare the accuracy of stone casts
      generated from a second pour of a properly handled alginate impression with first
      poured casts. A maxillary dentoform was indexed with six reference spaces (#8-15,
      9-2, 2-15, and incisal-to-gingival of #3, 9, 14). Irreversible hydrocolloid
      (Jeltrate) impressions were made in perforated steel trays by a single
      investigator. Impression material was spatulated for 1 minute. The seated
      impression and dentoform were wrapped in a damp paper towel to simulate intraoral
      conditions, and allowed to set for 2 minutes. Upon separation, the impression was
      stored in a damp towel for 5 minutes. The impression was poured in cast stone
      (Microstone) according to the manufacturer's instructions. The stone-filled
      impression was immediately rewrapped in a damp paper towel and allowed to set for
      45 minutes at room temperature. Upon removal of the stone, the impression was
      rinsed with cold water, shaken dry, and repoured in the same manner. Ten
      impressions were made: the first five impressions were poured to make casts for
      Group A, then repoured as described above for casts for Group B. The remaining
      five impressions were poured once to make casts for Group C. The six spaces of
      each cast were measured three times in random order using a dial caliper and the
      space average calculated for the cast. At each space, analysis of variance showed
      no significant difference among Groups A, B, or C (P < 0.05). When alginate
      impressions that have been poured with cast stone are kept moist during stone
      setting and repoured within 45 minutes, two casts can be generated from one
      impression with the same degree of accuracy as two casts made from taking two
      separate impressions, providing the alginate does not tear during first cast
      removal.

PMID- 9656924
TI  - Weight change of various light-cured restorative materials after water immersion.
AB  - This study investigated weight changes of various light-cured glass-ionomer
      cements and other restorative materials during water immersion and compared
      findings with those of conventional glass-ionomer cement and light-cured resin
      composites. Three light-cured glass-ionomer cements, two polyacid-modified
      composite resins, one conventional glass-ionomer cement, and one light-cured
      composite resin were evaluated in this study. The weight changes of these
      specimens after water immersion were measured using an electronic analytical
      balance and adjusted according to water solubility measured at the same time
      weight change was measured. The results were analyzed by one-way ANOVA and
      Scheffe's F test at P < 0.05. The weight change of Photac-Fil Aplicap was the
      largest, and there were significant differences among the materials (P < 0.05).
      Weight change after 6 weeks' water immersion was noted in the following order:
      Fuji Ionomer Type II LC, Vitremer, Fuji Ionomer Type II, VariGlass VLC, Geristore
      V, and Clearfil AP-X. It is suggested that the amount of water sorption of light
      cured glass-ionomer cements is greater than that of polyacid-modified composite
      resins.

PMID- 9656925
TI  - Temperature and humidity effects on bond strength of a dentinal adhesive.
AB  - Dentin specimens from 46 extracted human molar teeth were used in a matched-pair
      design examining the factors of temperature/humidity on shear bond strength of a
      dentinal adhesive to dentin. For one tooth-half, all procedures using restorative
      materials were accomplished in a controlled temperature and humidity chamber
      (humidity 95.0 +/- 2.0%, temperature 37.0 +/- 0.3 degrees C). For the other
      matched tooth-half all procedures were performed at ambient room conditions
      (humidity 52%, temperature 23.3 degrees C/74 degrees F). Oil-free air and water
      were used in all restorative procedures. Application of Scotchbond Multi-Purpose
      Adhesive System was followed by placement of Z100 Restorative Resin, and
      thermocycling 1000 cycles from 5 to 55 degrees C. Each matched specimen was
      tested 24 hours later in an Instron Testing Machine. A paired t-test was
      performed for comparison of bond strength set values, since they were obtained
      from matching halves of the same teeth. Paired t-test comparison showed that the
      average humidity/temperature chamber mean of 7.14 +/- 3.12 MPa was significantly
      less than the ambient conditions mean of 14.29 +/- 5.07 (P = 0.0000). Bond
      strength testing under simulated oral conditions may produce significantly
      different findings than customary bench-top laboratory experiments.

PMID- 9656926
TI  - Resin-modified glass ionomers: dentin bond strength versus time.
AB  - Most dentin bond strength tests of resin-modified glass-ionomer cements have been
      conducted after at least 24 hours' storage in water. In a clinical situation,
      debonding might occur soon after the restoration was placed if subjected to
      stress. The purpose of this study was to investigate the rate of development of
      shear bond strength of resin-modified glass-ionomer cements, two Type IIs of
      which, Fuji II LC and Vitremer, were used. A conventional glass-ionomer cement,
      Fuji II, and a resin composite, Herculite XRV/OptiBond system, were also employed
      as controls. Bovine incisors were mounted in self-curing resin, and the facial
      surfaces wet ground with 600-grit SiC paper to expose dentin. Materials were
      condensed into a vinyl mold and bonded following the manufacturers' instructions.
      The shear bond strengths of 10 specimens per group were measured at a crosshead
      speed of 1.0 mm/minute after 1, 5, 10, 30, and 60 minutes' and 2, 5, and 24
      hours' storage in water at 37 degrees C. One-way ANOVAs followed by the Dunnet
      test (P < 0.05) were used to test for significant differences between the mean
      bond strength at 1 minute and each of the other test periods. The test period
      when there was a significant increase in bond strength was defined as the
      "initial increasing time." The dentin bond strengths of all the materials tested
      increased with prolonged storage time. The initial increasing times were 10
      minutes for Fuji II LC and OptiBond, 20 minutes for Fuji II, and 60 minutes for
      Vitremer. The differences in the initial increasing time might have clinical
      implications if the restoration is subjected to significant stress immediately
      after placement.

PMID- 9656928
TI  - How to present a claim for disability insurance.

PMID- 9656929
TI  - Speed temporaries, anterior and posterior.

PMID- 9656927
TI  - Effect of various infection-control methods for light-cure units on the cure of
      composite resins.
AB  - This study (1) compared the curing-light intensity with various barrier infection
      control methods used to prevent cross contamination, (2) compared the Knoop
      hardness value of cured composite resin when various barrier control methods were
      used, and (3) correlated the hardness of the composite resin with the light
      intensity output when different infection-control methods were used. The light
      cure unit tips were covered with barriers, such as cellophane wrap, plastic
      gloves, Steri-shields, and finger cots. The control group had no barrier.
      Composite resins were then cured for each of the five groups, and their Knoop
      hardness values recorded. The results showed that there was significant
      statistical difference in the light-intensity output among the five groups.
      However, there was no significant statistical difference in the Knoop hardness
      values among any of the groups. There was also no correlation between the Knoop
      hardness value of the composite resin with the light-intensity output and the
      different infection-control methods. Therefore, any of the five infection-control
      methods could be used as barriers for preventing cross-contamination of the light
      cure unit tip, for the light-intensity output for all five groups exceeded the
      recommended value of 300 W/m2. However, to allow a greater margin of error in
      clinical situations, the authors recommend that the plastic glove or the
      cellophane wrap be used to wrap the light-cure tip, since these barriers allowed
      the highest light-intensity output.

PMID- 9656930
TI  - New paradigms for anterior tooth preparation. Rationale and technique.
AB  - A biologic and esthetic rationale has been presented along with a simplified
      controlled technique to achieve predictable results (Figures 13A and 13B). The
      clinician is constantly faced with the challenge of developing room for esthetic
      material while preserving the biologic objectives. Using the three essential
      anterior tooth preparation keys (incisal edge, reduction requirements, and the
      biologic zone) enhances predictability. Developing the incisal edge relative to
      the dynamics of facial esthetics provides the initial starting point of tooth
      preparation. The reduction requirements are designed to satisfy the mechanical
      principles, address the pulpal concerns, and preserve the structural requirements
      of the tooth. The biologic zone can be developed by using the total dentogingival
      complex measurements and will clinically aid in the determination of cervical
      limitations to providing intracrevicular margin location.

PMID- 9656931
TI  - The Tenax Dental Implant System. Rationalized implant treatment using
      conventional prosthodontics.

PMID- 9656932
TI  - Choosing the right clinical camera. Part I.
AB  - Our recommendation is a 90-105 mm macro lens focusing from 1:1 to infinity and a
      minimum aperture of f/32. A reputable brand should be preferred: Nikon, Canon,
      Minolta, Sigma etc.... A 105 mm macro lens allows for adequate working distance
      (approx. 130 mm for a straight view at 1:1 magnification). A 105 mm macro lens
      induces insignificant perspective distortion and has a large range of aperture.
      Lastly, it provides for a magnification scale ranging from 1:1 to infinity and is
      optically excellent. The working distance of current camera systems extends
      approximately from 4 4/8" or 114 mm, to 7" or 180 mm, at 1:1 magnification. Again
      these differences are mainly due to lens design and mounted components, (filters,
      bracket, lighting systems). A minimum of 5" or 125 mm of working distance is
      desirable for physical access of your camera and proper illumination of the
      photographed object. However, adequate lighting also depends upon the type and
      location of your lighting system especially for higher magnification photographs.
      Part II will examine the different lighting systems on the market and try to
      decide which is most adapted to your needs. It will answer your questions about
      the use of the operatory light while focusing, the red eye problem and the use of
      polarizing filters to decrease the amount of reflection from the flash.

PMID- 9656933
TI  - A five year study. Fluoride release of four reinforced composite resins.
AB  - PURPOSE: The purpose of this study was to record the fluoride released measured
      in parts per million of four fluoride composite resins for five years. MATERIALS
      AND METHODS: Four fluoridated composites were separated into four groups. Two
      composite resins with high viscosity were core materials, Ti-Core with titanium
      (group 1) and Ti-Core Natural (group 2) and the other two resins studied were low
      viscosity post cements Flexi-Flow cement with titanium (group 3) and Flexi-Flow
      Natural (group 4). The fluoride release was studied under four experimental
      conditions. Three replications were studied in each condition. Fluoride release
      was measured for 260 weeks (5 years). STATISTICAL METHODS: A one-way analysis of
      variance (ANOVA) was used to compare the average weekly release followed by a
      Student-Newman-Keuls (SNK) pairwise multiple comparison test. All results were
      considered statistically significant if p < 0.05. RESULTS: The ANOVA analysis
      released a significant statistical interaction between group and week (p <
      0.0001). Further analysis showed that the average weekly release for Ti-Core with
      titanium did not differ from Ti-Core Natural, and that Ti-Core with titanium and
      Ti-Core Natural differed from both Flexi-Flow Natural and Flexi-Flow with
      titanium, which were not different from one another. CONCLUSIONS: Ti-Core with
      titanium (Group 1) and Ti-Core Natural (Group 2) released a greater amount of
      fluoride than Flexi-Flow with titanium (Group 3) and Flexi-Flow Natural (Group
      4). The fluoride released from these fluoridated resin composites are similar to
      reported ranges of other fluoride releasing dental restoration materials.

PMID- 9656934
TI  - Profiting from restorative dentistry.

PMID- 9656935
TI  - Infectious diseases: their impact on dentistry.

PMID- 9656936
TI  - The MGDS examination: a systematic approach. 2. Part II of the examination: log
      diary presentation, patient selection and assessment.
AB  - This paper is the second in a series of four which present a systematic approach
      to colleagues who are preparing for and sitting the examination for the Diploma
      of Membership in General Dental Surgery (MGDS) of The Royal College of Surgeons
      of England. Although some details may differ, the general principles set out in
      the four papers apply equally to the MGDS examinations of the other Royal
      Surgical Colleges.

PMID- 9656937
TI  - The correlation between selected factors which influence dental aesthetics.
AB  - This study evaluated the inter-relationship between five aesthetic factors: the
      form of the face, tooth and arch, maxillary anterior tooth arrangement and
      palatal contour. An assessment was made to determine if correlation was
      sufficient to recommend their use as reliable aesthetic factors for the selection
      of suitable tooth moulds for edentulous and partially edentulous patients. This
      would enable the clinician to select a tooth mould at the chairside, based on an
      evaluation of the individual's aesthetic factors where, for example, the
      maxillary incisors should have the same outline shape as the individual's face. A
      computer program was developed incorporating images of the factors taken from 50
      Caucasian adults aged 20-31 years and assessment of correlation made by outline
      superimposition and classification. The objectives were to design a computer
      program to analyse, classify and evaluate correlation between the five factors in
      each case by superimposition and classification. Correlation by superimposition
      recorded some concurrence between forms. The findings of this study suggest that
      there was insufficient correlation to support Nelson's 'Aesthetic Triangle', or
      Williams' face form/tooth theory. The incidence of correlation by classification
      between anterior tooth arrangement and arch form was sufficiently high to suggest
      their value as an aesthetic aid.

PMID- 9656938
TI  - Transverse expansion in the upper arch.
AB  - The decision as to when to refer patients with transverse problems and when to
      undertake expansion can be confusing. This paper explains the situations when
      expansion should be undertaken and also covers the methods of treatment currently
      available.

PMID- 9656939
TI  - Biocompatibility of dentine-bonding agents. 2. Pulpal considerations.
AB  - The paper reviews the literature concerning the biocompatibility of dentine
      bonding agents. The literature review indicates that two main hypotheses are
      presented to explain pulpal inflammation following the placement of materials
      such as dentine-bonding agents, namely material toxicity and bacterial infection.
      The paper discusses the role of such factors as microbial microleakage, remaining
      dentine thickness and the smear layer as factors in determining material toxicity
      and summarises the reported biocompatibility studies. From this it is concluded
      that most bonding agents contain constituents which have a potential irritant or
      toxic effect on the pulpo-dentinal complex. The irritant effect may be due to
      constituents of the bonding agents, or to poor or lost bonding, or to a
      combination of all these factors. The recently favoured total-etch technique may
      cause an increase in dentine permeability by removal of the smear layer and
      thereby increase the irritant effect of some materials.

PMID- 9656940
TI  - The impact of computers in dental education.
AB  - Computer technology is increasingly influencing many aspects of our lives and
      will continue to do so in the future. This paper discusses the impact of
      computers in dentistry; how their use is radically changing the way practices are
      run and the way under/postgraduate dental education is evolving, by incorporating
      computer-aided learning (CAL) material as an efficient and convenient educational
      tool. Greater computer literacy may result in a future where there is a shift
      away from traditional centres of learning to computer conferencing and distance
      learning.

PMID- 9656941
TI  - Evaluation of chest pain in low-risk patients presenting to the emergency
      department: the role of immediate exercise testing.
AB  - STUDY OBJECTIVES: To determine the safety and utility of immediate exercise
      testing in the evaluation of low-risk patients presenting to the emergency
      department with chest pain and its applicability to a heterogeneous population of
      men and women. METHODS: We conducted a prospective study of the safety and
      utility of immediate exercise testing in low-risk patients, as indicated by
      clinical and ECG criteria. The study group was large, heterogeneous, and included
      patients with a history of coronary artery disease. The patients were treated at
      a large, university medical center. Exercise testing (immediate exercise
      treadmill testing) was performed by internists, and cardiac serum enzyme levels
      were not measured before the exercise test. RESULTS: A total of 212 patients (121
      men, 91 women) underwent exercise testing with no adverse effects. Twenty-eight
      (13%) patients had positive results on exercise ECGs. Twenty-three of the latter
      had further evaluation that revealed evidence of coronary artery disease in 13
      (57%). Fifty-nine percent (125/212) of patients had negative exercise test
      results and 28% (59/212) had nondiagnostic tests. All patients with negative test
      results and 93% with nondiagnostic test results were discharged directly from the
      ED. Thirty-day follow-up was achieved in 201 (95%) patients and revealed no
      mortality in any of the patients in the three groups. One patient with a positive
      exercise test result returned to the ED within 30 days with mild congestive heart
      failure. CONCLUSION: Our results in this patient population support the safety
      and utility of immediate exercise testing of low-risk patients who present to the
      ED.

PMID- 9656942
TI  - Multicenter comparison of two clinical decision rules for the use of radiography
      in acute, high-risk knee injuries.
AB  - STUDY OBJECTIVE: Two separate clinical decision rules, one developed in Ottawa
      and the other in Pittsburgh, for the use of radiography in acute knee injuries
      have been previously validated and published. In this study, the rules were
      prospectively validated and compared in a new set of patients. METHODS: A
      prospective, blinded, multicenter trial was conducted in the emergency
      departments of three urban teaching hospitals. A convenience sample of 934
      patients with knee pain requiring radiographs was enrolled. A standardized data
      form was completed for each patient, comprising the 10 clinical variables
      included in the two rules. Standard knee radiographs were then taken in each
      patient. The rules were interpreted by the primary investigator on the basis of
      the data sheet and the final radiologist radiograph reading. RESULTS: In the 745
      patients in whom the Pittsburgh rules could be applied there were 91 fractures
      (12.2%). The use of the Pittsburgh rule missed one fracture, yielding a
      sensitivity of 99% (95% confidence interval [CI], 94% to 100%); the specificity
      was 60% (95% CI, 56% to 64%). The Ottawa inclusion criteria were met by 750
      patients, with 87 fractures (11.6%). The Ottawa rule missed three fractures, for
      a sensitivity of 97% (95% CI, 90% to 99%); specificity was 27% (95% CI, 23% to
      30%). CONCLUSION: Prospective validation and comparison found the Pittsburgh rule
      for knee radiographs to be more specific without loss of sensitivity compared
      with the Ottawa rule.

PMID- 9656943
TI  - Validation of the Ottawa ankle rules in France: a study in the surgical emergency
      department of a teaching hospital.
AB  - STUDY OBJECTIVE: To validate the Ottawa ankle rules to predict fractures in a
      French clinical setting when they are used by physicians not involved in their
      development. METHODS: We used a prospective patient survey by emergency
      physicians in a surgical emergency department of a university teaching hospital
      of the Assistance Publique-Hopitaux de Paris. The study group consisted of 416
      consecutive patients aged 18 years and older who presented with acute ankle or
      midfoot injuries in the surgical ED during a 4-month period. Radiography was
      performed in each patient after clinical evaluation findings were recorded.
      RESULTS: Forty-nine ankle and 22 midfoot fractures were diagnosed. The decision
      rules had a sensitivity of .98, a specificity of .45, and a negative predictive
      value of .99 in detecting ankle fractures, a sensitivity of 1.0, a specificity of
      .29, and a negative predictive value of 1.0 in detecting midfoot fractures. The
      rules failed to predict one avulsion fracture in the ankle group. Application of
      these rules by emergency physicians would have reduced ankle or midfoot
      radiography requests by 33%. CONCLUSION: Use of the Ottawa ankle rules by French
      emergency physicians not involved in the rules' development resulted in 99%
      sensitivity and had a potential of reducing radiography requests by 33%.

PMID- 9656944
TI  - Factors influencing hospital transport of patients in continuing cardiac arrest.
AB  - STUDY OBJECTIVE: Prior research has established the futility of continued
      resuscitation efforts for patients in cardiac arrest who fail to respond to out
      of-hospital advanced cardiac life support. Determination of both medical and
      nonmedical factors resulting in the transport of patients in continuing cardiac
      arrest to the hospital may encourage the development of new systems or strategies
      to increase the appropriateness of these transports. METHODS: The attending
      paramedic completed a prospective survey after unsuccessful resuscitation efforts
      in our urban, hospital-based, two-tier emergency medical services (EMS) system.
      All nontraumatic adult arrests were included unless they were clearly noncardiac
      in nature. RESULTS: Paramedics responded to 259 cardiac arrests between September
      12, 1996, and April 31, 1997. Seventy-nine patients were pronounced dead without
      resuscitation efforts. Of the remaining 180 patients, 44 had return of
      spontaneous circulation and were transported to the hospital, 68 were pronounced
      dead in the field, and 68 were transported to the hospital in continuing cardiac
      arrest. The 68 patients transported while in cardiac arrest are the focus of this
      study. Rare problems with field termination were identified. Reasons for
      transport of the 68 patients in continuing cardiac arrest included arrest in
      ambulance or going to ambulance (n = 6), arrest in a public place (n = 17),
      environmental factors (n = 6), road hazard to paramedics (n = 1), possible
      reversible cause (n = 4), persistent ventricular dysrhythmia (n = 5), no
      intravenous access (n = 5), airway difficulties (n = 5), family unable to accept
      field termination (n = 3), cultural or language barrier (n = 1), EMS physician
      ordered transport (n = 1), and obesity (n = 1). A protocol allowing pronouncement
      of death in the ambulance and transport of the body to a designated area could
      have prevented lights-and-siren transport to the emergency department in 24 of
      the 68 cases. CONCLUSION: Factors other than medical ones often influence the
      decision to transport patients in continuing cardiac arrest. In our urban system,
      physician, medical examiner, and paramedic education and protocols were needed to
      aid decision-making in this situation.

PMID- 9656945
TI  - Prehospital oral endotracheal intubation by rural basic emergency medical
      technicians.
AB  - STUDY OBJECTIVE: To determine whether basic emergency medical technicians (EMT-B)
      can perform prehospital oral endotracheal intubation with success rates
      comparable to those of paramedics. METHODS: This was a nonrandomized, controlled
      trial using historical controls. Seven basic life support emergency medical
      services systems in six counties and their corresponding emergency departments in
      rural Indiana participated. Eighty-seven full-time EMTs with no prior or
      concurrent paramedic training volunteered for intubation training. Apneic
      prehospital patients aged 16 years or older without an active gag reflex or
      massive facial trauma were eligible for intubation and study enrollment. The EMTs
      completed a 9-hour didactic and airway manikin training course in direct
      laryngoscopic endotracheal intubation. The course was adapted from the national
      paramedic curriculum. RESULTS: Thirty-four (39%) of the EMT-Bs attempted to
      intubate 57 eligible patients. In 49.1% of these patients, successful
      endotracheal tube placement was confirmed by the receiving physician (95%
      confidence interval, 36.4% to 61.9%); in contrast, the prehospital intubation
      success rates from three previous studies of manikin-trained paramedics ranged
      from 76.9% to 90.6% (P < .001). Complications included five (9%) inadvertent
      extubations, two endotracheal tube cuff ruptures, two prolonged intubation
      attempts, and one mainstem bronchus intubation. There were no unrecognized
      esophageal intubations. Two of the seven EMS agencies did not report any
      intubation data. CONCLUSION: Rural EMTs with didactic and airway manikin training
      failed to achieve prehospital intubation success rates comparable to those of
      paramedic controls. Possible explanations include training deficiencies, poor
      skill transference from manikin to human intubation, infrequent intubation
      experiences, and inconsistent supervision.

PMID- 9656946
TI  - Prospective field study of violence in emergency medical services calls.
AB  - STUDY OBJECTIVE: To investigate the nature and frequency of violence encountered
      by EMS personnel. DESIGN: We conducted a prospective, observational case-series
      study of a city-county EMS system serving a population of 500,000. RESULTS: We
      analyzed 297 EMS runs over 737 hours of observation. The Overt Aggression Scale
      (OAS) was used to assess each violent episode. There were 239 (81%) nonviolent
      runs, 16 (5%) violent runs, and 42 (14%) violent runs that occurred after a
      violent episode had taken place (postviolent runs). This was a frequency of one
      violent episode for every four 12-hour shifts, or for every 19 runs. The violent
      behaviors included verbal aggression solely in 50% (n = 8), physical aggression
      solely in 13% (n = 2), and both verbal and physical aggression in 38% (n = 6).
      One episode involved an unsecured weapon. CONCLUSION: These data indicate that
      violent situations occur in 5% of calls in this EMS system. The fact that an
      additional 14% of calls are precipitated by the results of violence may influence
      perceptions by EMS personnel of danger and frequency of exposure to unstable
      situations. Exposure to violence is underreported in our EMS documentation.

PMID- 9656947
TI  - Trends in firearm-related injuries in Washington State, 1989-1995.
AB  - STUDY OBJECTIVES: To describe the incidence and outcome of firearm-related
      injuries and to describe trends over time. DESIGN: Information about firearm
      related injuries in Washington state was extracted from computerized death
      certificate and hospital discharge files for the period 1989 through 1995. Cases
      seen only in emergency departments were estimated using initial results from a
      statewide firearm injury surveillance system. RESULTS: An estimated 9,995 persons
      were shot during the 7-year period (incidence 28.0/100,000 person-years); 2,944
      persons (29%) required ED care only, 2,864 persons (29%) were hospitalized and
      survived, and 4,187 persons (42%) died. Survival was lowest for suicide attempts
      (11%), intermediate for assaults (68%), and greatest for unintentional shootings
      (96%). Most deaths (91%) occurred before hospital admission. From 1989 to 1995,
      the incidence of firearm-related injuries showed little change: an increase of
      4.5%. However, suicidal shootings among persons younger than 35 years increased
      by 31.3%, and the incidence of firearm-related assaults rose by 53.7% among
      persons of all ages. Survival among all persons who were shot and among
      hospitalized shooting victims showed little change over time. CONCLUSION: Firearm
      related suicides among the young and assault-related shootings among all persons
      increased. The estimated proportion of shooting victims who survived did not
      change over time.

PMID- 9656948
TI  - Criminal activity and assault-type handguns: a study of young adults.
AB  - STUDY OBJECTIVE: We studied a population of young adults who legally purchased
      handguns to determine whether an association exists between the purchase of an
      assault-type handgun and prior or subsequent criminal activity. METHODS: We
      conducted a longitudinal study of 5,360 legally authorized purchasers of handguns
      in California in 1988 who were younger than 25 years at the time of purchase. Our
      main outcome measures were (1) adjusted relative risk (RR) for the purchase of an
      assault-type handgun for subjects with a criminal history compared with subjects
      without such a history and (2) adjusted RR for new criminal activity during the 3
      years after handgun purchase for purchasers of assault-type handguns compared
      with purchasers of other handguns. RRs were adjusted for sex and race/ethnicity.
      RESULTS: Handgun purchasers with a criminal history were more likely than those
      with no criminal history to purchase assault-type handguns (4.6% and 2.0%,
      respectively; RR = 2.0; 95% confidence interval [CI] 1.5 to 2.8). Among handgun
      purchasers who had a criminal history, purchasers of assault-type handguns were
      more likely than purchasers of other handguns to be charged with new offenses (RR
      = 1.5; 95% CI, 1.3 to 1.9), including offenses involving firearms of violence (RR
      = 1.7; 95% CI, 1.3 to 2.20. Among those who had previously been charged with
      Violent Crime Index offenses (murder, rape, robbery, aggravated assault), those
      who purchased assault-type handguns were more than twice as likely as purchasers
      of other handguns to be charged with a new offense (RR = 2.3; 95% CI, 1.5 to 3.4)
      and three times as likely to be charged with a new offense involving firearms or
      violence (RR = 3.0, 95% CI, 1.9 to 4.6). CONCLUSION: In this population, the
      purchase of an assault-type handgun was associated with both prior and subsequent
      criminal activity.

PMID- 9656949
TI  - Trends in nonfatal and fatal firearm-related injury rates in the United States,
      1985-1995.
AB  - STUDY OBJECTIVE: To characterize trends in annual estimates of nonfatal firearm
      related injuries treated in US hospital emergency departments and to compare
      trends in quarterly rates of such injuries with those of firearm-related
      fatalities in the US population. METHODS: Data on nonfatal firearm-related
      injuries were obtained from the National Electronic Injury Surveillance System
      (NEISS) by review of medical records for June 1, 1992, through May 31, 1995. Data
      on firearm-related fatalities were obtained from the National Vital Statistics
      System for January 1, 1985, through December 31, 1995. NEISS comprises 91
      hospitals that represent a stratified probability sample of all hospitals in the
      United States and its territories that have at least six beds and provide 24-hour
      emergency service. The main outcome measures were numbers, percentages, and
      quarterly population rates for nonfatal and fatal firearm-related injuries.
      RESULTS: An estimated 288,538 nonfatal firearm-related injuries (95% confidence
      interval [CI], 169,776 to 407,300) were treated in EDs during the 3-year study
      period. The annual number of non-fatal firearm-related injuries increased from
      99,025 for June 1992 through May 1993 (95% CI, 58,266 to 139,784) to 101,669 for
      June 1993 through May 1994 (95% CI, 59,822 to 143,516), then decreased to 87,844
      for June 1994 through May 1995 (95% CI, 51,687 to 124,001). Before the third
      quarter of 1993, quarterly nonfatal and fatal firearm-related injury rates in the
      total US population and quarterly nonfatal firearm assaultive injury and firearm
      homicide rates for males aged 15 to 24 years were observed to be on the rise.
      Since then, these rates have significantly declined. CONCLUSION: Analysis of
      national trends indicates that non-fatal and fatal firearm-related injuries are
      declining in the United States, although the rate of firearm-related deaths
      remains high, especially among males aged 15 to 24 years, in relation to other
      leading causes of injury death. An assessment of factors responsible for the
      decline in firearm-related injuries is needed to design further prevention
      efforts.

PMID- 9656950
TI  - Handgun purchase trends, Washington state: differences by age of buyer.
AB  - STUDY OBJECTIVES: To examine trends in legal handgun purchases from federally
      licensed dealers and specifically to describe recent changes in age and gender of
      purchaser and caliber of handguns purchased. METHODS: A cohort study was
      performed of the adult population of Washington state from 1950 through 1992
      using a state dealer record of handgun sales database. The purchase of handguns
      from licensed dealers was expressed as the number purchased per 100,000
      population per year. RESULTS: The handgun purchase rate increased for the total
      population between 1950 and 1992, from 169 to 2,076 per 100,000 persons. Between
      1983 and 1992, the purchase rate among men aged 21 to 24 years increased 184%;
      among women of this age group, the rate increased 127%. Among men aged 21 to 24
      years, the rate of 9 mm handgun purchases increased 1,682% between 1983 and 1992,
      the greatest increase for any age-caliber category. CONCLUSION: The greatest
      increase in rate of legal handgun purchases in Washington state from 1983 through
      1992 was among the youngest purchasers. Sales of 9 mm handguns increased most
      rapidly, especially among the youngest buyers.

PMID- 9656951
TI  - The next-generation emergency department.
AB  - The greatest advances in medicine over the next two decades will result from
      application of the tools and principles of informatics to the problems of
      clinical medicine. New developments in medical informatics will drive advances in
      clinical care administration, research, and education. Information flow in the
      emergency department a decade hence will be characterized by a transformation
      from a "hunter-gatherer" information model to a "publisher-subscriber" model in
      which the right information will always be available at the right time. In large
      part, information will be gathered automatically rather than manually. Computers
      will be ubiquitous and almost invisible. Invasive and attached monitoring and
      testing will yield to new remote and noninvasive technologies. Information will
      be shared and modified as needed, rather than recreated and reentered by each
      caregiver. Eventually, the use of information technologies in the emergency
      medicine workplace will enhance our traditional role as hands-on providers of
      direct patient care.

PMID- 9656952
TI  - EM3M: envisioning the future of emergency medicine.

PMID- 9656953
TI  - Preventing firearm injuries.

PMID- 9656954
TI  - ACEP endorsement of the EAST position paper on firearms violence.

PMID- 9656955
TI  - Emergency medicine in Hong Kong.
AB  - Emergency medicine in Hong Kong is a relatively new specialty. Substantial
      progress toward recognition of emergency medicine in the territory has occurred
      during the past 2 years, and the Hong Kong College of Emergency Medicine is now
      formally recognized by the Royal College of Surgeons in the United Kingdom. With
      the transfer of the territory to chinese rule, the emergency medical system in
      Hong Kong may serve as a model for the development of emergency medicine in
      mainland China.

PMID- 9656956
TI  - United States physician assistance in development of emergency medicine in
      Hangzhou, China.
AB  - Emergency medicine is growing rapidly as a specialty and is beginning to be
      recognized as an essential component of medicine in China. Traditional Chinese
      medicine and modern technology exist together. A description of the US authors'
      experience as consultants at a new emergency department and in establishing an
      emergency medicine residency program in Hangzhou, China is provided. A total of 7
      months were spent in the observation, identification, and development of a basic
      framework of emergency care at a new hospital. The practice of emergency medicine
      in China was researched by direct observation at several Chinese cities and by
      literature review. China is taking the parts of the Western system it can use and
      implementing its own methods in the overall practice of emergency medicine.

PMID- 9656957
TI  - Emergency medicine in Thailand.
AB  - Typical of developing countries, Thailand, located in Southeast Asia, is only
      beginning to consider the importance of emergency medicine and prehospital care.
      Medical emergencies in Thailand have traditionally had relatively high rates of
      occurrence and are currently increasing in the context of rapid economic
      development and urbanization, yet no formal emergency care training for
      physicians or prehospital care workers exists.

PMID- 9656958
TI  - Acute right lower quadrant pain in a patient with leukemia.
AB  - Typhlitis or neutropenic enterocolitis is a life-threatening, necrotizing process
      of the cecum whose incidence is increasing. It is usually encountered in patients
      with leukemia who have recently undergone chemotherapy. Neutropenic enterocolitis
      presents as fever, abdominal pain, and diarrhea in neutropenic patients. As the
      incidence of neutropenic enterocolitis increases, emergency physicians must be
      aware of this rapidly progressive and potentially fatal disease.

PMID- 9656959
TI  - Dexfenfluramine overdose.
AB  - Dexfenfluramine (Redux), the dextro-rotatory (+) steroisomer of fenfluramine, was
      previously approved for the treatment of weight control in the United States. We
      report a case of acute dexfenfluramine ingestion characterized by coma, clonus,
      and respiratory failure.

PMID- 9656960
TI  - Hyperkalemic ascending paralysis.
AB  - Hyperkalemia is a life-threatening electrolyte disturbance. The clinical
      presentation is most commonly related to its effects on cardiac conductivity and
      contractility, although weakness and respiratory compromise may occur. We
      describe what we believe to be the first reported case of life-threatening
      hyperkalemia presenting as an ascending paralysis which was associated with
      standard-dose trimethoprim-sulfamethoxazole therapy. The patient had mild,
      underlying renal disease which predisposed him to develop hyperkalemia. This case
      underscores the need to use caution in prescribing trimethoprim to such patients.

PMID- 9656961
TI  - Update: human ehrlichiosis--Maryland and Wisconsin, 1994.

PMID- 9656962
TI  - Universal health care: associated factors.

PMID- 9656963
TI  - Guidelines for care of the elderly.

PMID- 9656964
TI  - Guidelines for care of the elderly.

PMID- 9656965
TI  - Guidelines for care of the elderly.

PMID- 9656966
TI  - Positional asphyxia.

PMID- 9656967
TI  - Bull-riding injuries.

PMID- 9656968
TI  - Clinical management of early progressive renal failure.
AB  - In the era of managed health care, the primary physician will be required to play
      an active role in the management of patients with early renal failure. This
      section provides a comprehensive and practical approach to the management of such
      patients. Early recognition of renal failure and monitoring its progression
      require an understanding of the pitfalls of commonly used diagnostic tests. Tight
      control of hypertension, angiotensin-converting enzyme inhibition, and dietary
      protein restriction play important roles in delaying the progression of renal
      disease. Avoidance of additional renal insults such as nephrotoxic drugs and
      radiographic contrast prevents acceleration of renal demise. A variety of
      clinical manifestations, including dyselectrolytemias, hypertension,
      malnutrition, secondary hyperparathyroidism, and anemia may develop in patients
      with early renal failure. Timely referral to a nephrologist will facilitate
      planning for renal replacement therapy and may favorably affect eventual
      outcomes.

PMID- 9656969
TI  - Nephrolithiasis: acute management and prevention.
AB  - The primary care physician has a responsibility not only to recognize and treat
      acute stone passage but to ensure that the patient with recurrent stones has
      metabolic evaluation and appropriate preventive care. Renal colic is typically
      severe, radiates to the groin, is associated with hematuria, and may cause ileus.
      About 90% of stones that cause renal colic pass spontaneously. The patient with
      acute renal colic should be treated with fluids and analgesics and should strain
      the urine to recover stone for analysis. Highgrade obstruction or failure of oral
      analgesics to relieve pain may require hospitalization; a urinary tract infection
      in the setting of an obstruction is a urologic emergency requiring immediate
      drainage, usually with a ureteral stent. Several approaches are available when
      stones do not pass spontaneously, including extracorporeal shock wave
      lithotripsy, percutaneous lithotripsy, and ureteroscopic laser lithotripsy.
      Calcium stone disease has a lifetime prevalence of 10% in men and causes
      significant morbidity. Renal failure is unusual. Stone types include calcium
      oxalate, uric acid, struvite, and cystine. Stone analysis is particularly
      important when a noncalcareous constituent is identified. The majority of
      patients with nephrolithiasis will have recurrence, so prevention is a high
      priority. High fluid intake is a mainstay of prevention. Metabolic evaluation
      will indicate other appropriate preventive measures, which may include dietary
      salt and protein restriction, and use of thiazide diuretics, neutral phosphate,
      potassium citrate, allopurinol, and magnesium salts. Dietary calcium restriction
      may worsen oxaluria and negative calcium balance (osteoporosis).

PMID- 9656970
TI  - Diabetic nephropathy.
AB  - Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD)
      and accounts for 35% of the ESRD population in the United States. It results in
      considerable morbidity, mortality, and expense. The average cost of managing one
      diabetic patient with ESRD is approximately $50,000 a year. Over the last decade,
      several advances in the management of diabetic nephropathy have allowed
      physicians to intervene and retard the progression of renal failure in patients
      with diabetic nephropathy. Stalling the progression of renal failure allows
      patients to maintain a superior quality of life and saves society millions of
      dollars that can be allocated to other aspects of health care. The prevalence of
      diabetes mellitus continues to increase. With the continued advances in medical
      technology and care, persons with this disease will live longer, and the
      incidence of diabetic nephropathy will increase. Primary care physicians will
      have the most frequent contact with these patients and therefore will have the
      greatest potential to favorably affect their clinical course. This review focuses
      on the therapeutic interventions available to delay the progression of diabetic
      nephropathy. Clinicians should strive to secure euglycemia and obtain optimal
      blood pressure control in their patients. The unique renal-protective effects of
      angiotensin-converting enzyme inhibitors will be reviewed, as will the salutary
      effects of a low-protein diet, normalizing serum cholesterol, and the cessation
      of smoking. The optimal timing of dialysis access placement and the initiation of
      dialysis and transplantation will also be discussed.

PMID- 9656971
TI  - PET imaging studies in drug abuse.
AB  - In spite of the massive public health problem associated with drug abuse,
      effective treatments remain elusive. This is due in part to a relatively poor
      understanding of the neurochemical changes which drugs of abuse produce in the
      human brain and the relationship of these changes to the behavioral and addictive
      properties of drugs. With the development of modern imaging methods and a variety
      of labeled drugs and radiotracers, it has now become possible to track many
      aspects of drug pharmacokinetics and pharmacodynamics directly in the human brain
      and to relate these parameters to the behavioral and toxic properties of drugs.
      REVIEW: In this article, we will highlight some examples of the use of Positron
      Emission Tomography to measure drug pharmacokinetics and pharmacodynamics and
      their relationship to addiction and to toxicity.

PMID- 9656972
TI  - Prognostic factors in patients with methanol poisoning.
AB  - OBJECTIVE: To identify prognostic factors in methanol poisoning and determine the
      effect of medical interventions on clinical outcome. METHODS: Retrospective
      review of all patients treated for methanol poisoning from 1982 through 1992 at
      The Toronto Hospital. Presenting history, physical examination, results of
      laboratory tests, medical interventions, and final outcomes after hemodialysis
      were abstracted. RESULTS: Of 50 patients treated for methanol poisoning, 18 (36%)
      died, 32 (64%) survived. Seven of the 32 survivors sustained visual sequelae
      (22%), the remaining 25 (78%) recovered completely. Patients presenting with coma
      or seizure had 84% (16/19) mortality compared to 6% (2/31) in those without (p <
      0.001). Initial arterial pH < 7 was also associated with significantly higher
      mortality (17/19, 89% vs 1/31, 3%, p < 0.001). There were no differences in time
      from presentation to dialysis between survivors and fatalities (8.4 +/- 3.6 vs
      7.6 +/- 3.5 hours, p = 0.47). The deceased patients had higher mean methanol
      concentration than the survivors (83 +/- 53 vs 41 +/- 25 mmol/L, p = 0.004).
      Subgroup analysis of 19 patients presenting with visual symptoms who survived
      showed prolonged acidosis (5.4 +/- 2.3 vs 3.0 +/- 2.1 hours, p = 0.06) in those
      with persistent visual sequelae. CONCLUSIONS: Coma or seizure on presentation and
      severe metabolic acidosis, in particular initial arterial pH < 7, are poor
      prognostic indicators in methanol poisoning. Survivors presented with lower
      methanol concentrations. Patients with residual visual sequelae had more
      prolonged acidosis than those with complete recovery. Future studies will be
      needed to confirm the effect of correction of acidosis on final clinical outcome.

PMID- 9656973
TI  - A preliminary study of immunologic and hematologic profiles of peripheral blood
      from Nebraska farmers who apply pesticides to their fields.
AB  - OBJECTIVE: Laboratory studies have documented a wide range of pesticide-induced
      changes in the hematopoietic and lymphoreticular systems. Some of these are
      expressed as altered serum values, blood cell counts, and leucocyte functions.
      The goal of the present study was to determine whether these alterations were
      evident in peripheral blood of Nebraska farmers who applied pesticides to their
      fields. METHODS: An invitation to participate was mailed to 100 residents (70
      farmers; 30 controls) of Butler County, Nebraska. All respondents (51 farmers and
      21 controls) were enrolled and surveyed by written questionnaire for health
      status and pesticide use. Our analysis included 45 farmers and 18 controls. The
      farmers were divided into a high (n = 23) and a low (n = 22) pesticide use group.
      Statistical correlations of ten blood values with both pesticide use and age were
      evaluated, since pesticide use correlated with age. RESULTS: Four of the ten
      blood values correlated with pesticide use and age (Spearman Rho). In a multiple
      regression model, pesticide use (not age) proved to be a predictor of red blood
      cell count and hematocrit. In the same model, pesticide use was not a predictor
      of mean red cell volume or candida antigen-induced T-lymphocyte proliferation.
      Serum complement activity did not correlate with pesticide use among the farmers
      (n = 45) but was significantly reduced (ANOVA) in the high pesticide use group,
      compared to controls. CONCLUSIONS: A preliminary study of blood values in a small
      cohort of Nebraska farmers found no pesticide-associated effects on 1) leucocyte
      count, 2) antigen- and mitogen-stimulated T-cell proliferation, 3) mitogen
      stimulated B-cell proliferation, and 4) concentrations of serum IgG and IgM. The
      study found small but statistically significant pesticide-associated effects on
      red blood cells and serum complement.

PMID- 9656974
TI  - Zolpidem-associated hallucinations and serotonin reuptake inhibition: a possible
      interaction.
AB  - BACKGROUND: Zolpidem (Ambien) is a sedative believed to act exclusively at the
      benzodiazepine omega 1 receptor. Sporadic case reports of zolpidem-associated
      hallucinations have appeared over the past 5 years, and over the past 2 years,
      the Washington Poison Center received five reports of prolonged visual
      hallucinations associated with zolpidem. CASE REPORTS: All five patients reported
      experiencing visual hallucinations lasting from 1-7 hours soon after taking
      zolpidem. Most had been taking zolpidem for less than a week and all five were
      concurrently taking an antidepressant: sertraline, desipramine, fluoxetine,
      bupropion, or venlafaxine; two sought assistance at a hospital. DISCUSSION: The
      precise mechanism of zolpidem-associated hallucinations remains unknown. In some
      previously published cases, the zolpidem-associated hallucinations have been
      short in duration, lasting at most 30 minutes. In contrast, the five patients in
      our series and in five previously reported cases, the hallucinations were more
      persistent, lasting up to 7 hours. Of these ten cases with persistent symptoms,
      nine were concurrently taking antidepressants that inhibit serotonin-reuptake,
      despite the fact that zolpidem has no known serotonin-mediated mechanisms.
      CONCLUSIONS: These cases, plus prior case reports, suggest that a pharmacodynamic
      interaction between serotonin reuptake inhibition and zolpidem may lead to
      prolonged zolpidem-associated hallucinations in susceptible individuals.

PMID- 9656975
TI  - Poisoning severity score. Grading of acute poisoning.
AB  - BACKGROUND: A standardized and generally applicable scheme for grading the
      severity of poisoning allows a qualitative evaluation of morbidity and
      facilitates comparability of data. Working from a simple grading scale proposed
      by the European Association of Poisons Centres and Clinical Toxicologists, a
      Poisoning Severity Score has been developed jointly with the International
      Programme on Chemical Safety and the European Commission. METHODS: The Poisoning
      Severity Score has been elaborated, tested, and gradually revised during a
      project running 1991-1994. Fourteen poisons centers from various countries have
      participated. Each center independently graded 371 cases of acute poisoning by
      ten different toxic agents. The data were then analyzed and compared. RESULTS:
      The concordance in grading the severity increased during the study period, and in
      the last phase there was an acceptable concordance among centers in 80% or more
      of the cases. Given the condition and quality of the original case records, this
      result was considered satisfactory and agreement was reached on the scoring
      scheme presented here. The Poisoning Severity Score grades severity as (0) none,
      (1) minor, (2) moderate, (3) severe, and (4) fatal poisoning. It is intended to
      be an overall evaluation of the case, taking into account the most severe
      clinical features. Use of the Poisoning Severity Score normally requires a follow
      up of all cases, but may be used on admission or other times during the course of
      poisoning if this is clearly stated when data are presented. CONCLUSIONS: A
      Poisoning Severity Score has been developed and found applicable for grading the
      severity of poisoning. It is foreseen that the Poisoning Severity Score will meet
      the expectations and be used in practice, but its future use and evaluation may
      result in some further revision and refinement.

PMID- 9656976
TI  - The prospective value of the IPCS/EC/EAPCCT poisoning severity score in cases of
      poisoning.
AB  - INTRODUCTION: The poisoning severity score is a four-point severity
      classification scale, developed by the International Programme on Chemical
      Safety, the Commission of the European Union, and the European Association of
      Poison Centres and Clinical Toxicologists (IPCS/EC/EAPCCT), for the retrospective
      assessment of cases of poisoning reported to poisons information centers.
      OBJECTIVES: The aims of this study were to test the validity of using the
      poisoning severity score obtained at initial referral to assess clinical severity
      and the likelihood of subsequent deterioration, to select cases for follow-up,
      and also to determine the need for referral to a clinical toxicologist. METHODS:
      The poisoning severity score was determined at the time of initial inquiry.
      Follow-up was then undertaken until either the patient was discharged from
      medical attention or died. A second poisoning severity score was then calculated
      taking note of the most severe features present after the initial inquiry.
      RESULTS: Of 718 consecutive telephone inquiries, 397 were given an initial
      poisoning severity score of 0 (no signs and symptoms), 225 a score of 1 (mild
      symptoms), 71 a score of 2 (moderate symptoms), and 25 a score of 3 (severe
      symptoms). Follow-up data are available only in 638 cases because the patient or
      referring doctor could not be traced in 80 instances. Of the 638 cases, 41
      deteriorated; 31 of these were graded initially as poisoning severity score 0,
      four as 1, and six as 2. Five patients died (two with an initial score of 2 and
      three with an initial score of 3). CONCLUSIONS: This study demonstrates that it
      is useful to score telephone inquiries to a poisons information service at
      initial referral with the poisoning severity score. First, the poisoning severity
      score is helpful in assessing accurately the clinical severity and the likelihood
      of further deterioration. Second, the poisoning severity score is useful in
      determining the need for referral of the inquiry to a clinical toxicologist, thus
      ensuring that more serious and complicated cases of poisoning receive expert
      medical advice on management. Third, the poisoning severity score is helpful in
      selecting those cases which warrant follow-up for medical and epidemiological
      reasons.

PMID- 9656977
TI  - Is the yew really poisonous to you?
AB  - BACKGROUND: Taxus species, commonly referred to as yew plants, have the
      reputation of being inordinately toxic. Case reports which chronicle human near
      fatal yew berry ingestions and countless fatalities in livestock present a sober
      profile to the treating toxicologist. Very often, a limited number of adverse
      reports influence decisions on all exposures to that potential poison. The
      objective of this investigation was to profile the toxicity of exposures to Taxus
      spp and determine what percentage of exposures were associated with significant
      morbidity. METHODS: The individual computerized files of all exposures to Taxus
      spp were retrieved from American Association of Poison Control Centers (AAPCC)
      Toxic Exposure Surveillance System (TESS) and placed in a relational database.
      Reports from 1985-1994 were analyzed. The cases were examined to determine
      patient demographics, the outcome of exposures, the ultimate disposition of the
      patients, treatment, and symptoms. AAPCC TESS definitions were used to assess
      outcomes. RESULTS: The number of exposures identified from the 10-year subset was
      11,197. Children less than 12 years of age were involved in 96.4% (< 6 years
      92.7%; 6-12 years, 3.7%) of the exposures. When the final outcome of the exposure
      was documented (n = 7269), no adverse effects occurred in 92.5% and minor effects
      were experienced in 7.0%. Moderate (more pronounced, but not life-threatening)
      effects were experienced by 30 individuals and major (life-threatening) effects
      occurred in 4 people. There were no fatalities. Decontamination therapy, when
      compared to no therapy, had no impact on patient outcome. 6.3% were admitted for
      psychiatric or medical care. When symptoms were related to Taxus spp exposures,
      the most frequent symptoms were gastrointestinal (65.5%), followed by dermal
      (8.3%), neurological (6.0%), and cardiovascular (6.0%). DISCUSSION: There are
      limitations to the interpretation of AAPCC TESS data which may lead to bias in
      favor of positive outcomes. However, the large sample size may minimize the
      limitations. CONCLUSION: Taxus spp exposures result only rarely in significant
      morbidity. Consistent with published case reports, the most common symptoms were
      gastrointestinal. Decontamination had no impact on patient outcome.

PMID- 9656978
TI  - Poison centers and plants: more pollyanna data?

PMID- 9656979
TI  - Pediatric benzodiazepine ingestion resulting in hospitalization.
AB  - OBJECTIVE: To characterize the clinical findings in children hospitalized for
      benzodiazepine ingestion. METHOD: Retrospective case series in two urban
      children's hospitals, with no intervention. Suicide attempts and polypharmacy
      ingestions were excluded. RESULTS: Forty-six children (67% male) with a mean age
      of 36 months (range 14-127 months) were hospitalized from January 1987 through
      September 1994. Lorazepam was most frequently ingested (13/41 identified drugs,
      32%). The most prevalent symptoms were ataxia (87%), lethargy (57%), coma
      (Glasgow coma score < 15, 35%; Reed coma score > 0, 22%), and respiratory
      depression (9%). Duration of symptoms was less than 24 hours in 88% of patients.
      Isolated ataxia occurred in eight patients; in five of these patients,
      benzodiazepine ingestion was unsuspected by the physicians. Three parents
      intentionally administered the benzodiazepine to their child. Only 50% of 32
      toxicology screens were positive for benzodiazepines. One child required
      endotracheal intubation. Flumazenil administration preceded clinical improvement
      in two other children. The remaining patients received activated charcoal
      administration and supportive care. CONCLUSION: Children hospitalized for
      benzodiazepine overdose occasionally had life-threatening symptoms. Ataxia was
      the most common clinical finding following benzodiazepine ingestion in this
      series. Flumazenil appeared beneficial for the treatment of severe benzodiazepine
      toxicity in only two patients. Most children recovered from their overdose
      uneventfully after receiving activated charcoal and supportive care.

PMID- 9656980
TI  - Peripheral polyneuropathy due to chronic use of topical ammoniated mercury.
AB  - BACKGROUND: Despite their potentially disastrous side effects, topical mercury
      salts can still be found as ingredients in some over-the-counter preparations or
      local remedies. CASE REPORT: Peripheral polyneuropathy as a result of chronic
      ammoniated mercury poisoning was studied and followed over 2 years. A 36-year-old
      man developed peripheral polyneuropathy following chronic perianal use of an
      ammoniated mercury ointment. Highly elevated blood and urine mercury levels were
      found. Sural nerve biopsy showed mixed axonal degeneration-demyelination. There
      was progressive improvement of his symptoms over 2 years but neurophysiological
      examination revealed incomplete recovery. CONCLUSION: The availability of safer
      drugs should result in a complete ban of these dangerous compounds.

PMID- 9656981
TI  - Massive sulfasalazine and paracetamol ingestion causing acidosis, hyperglycemia,
      coagulopathy, and methemoglobinemia.
AB  - CASE REPORTS: Reports of acute toxicity following sulfasalazine ingestion are
      rare. A case of an acute ingestion of sulfasalazine 50 g and paracetamol 50 g
      resulting in severe lactic acidosis, seizures, coagulopathy, hyperglycemia,
      ketosis, and methemoglobinemia is reported. Despite the ingestion of a large
      amount of paracetamol with serum paracetamol 5486 nmol/L (844 mg/L), significant
      hepatotoxicity did not occur. The patient recovered fully following
      administration of intravenous N-acetylcysteine, methylene blue, sodium
      bicarbonate, and supportive therapy.

PMID- 9656982
TI  - Fatality resulting from intraventricular vincristine administration.
AB  - BACKGROUND: Inadvertent intrathecal administration of vincristine has been
      reported and is uniformly fatal except in two of three cases treated with spinal
      fluid exchange. We report a case of inadvertent direct intraventricular
      vincristine administration. CASE REPORT: A 59-year-old woman developed acute
      lymphocytic leukemia with meningeal involvement and was being treated with
      intraventricular cytarabine (beta-cytosine arabinoside, Ara-C) injected via an
      Ommaya reservoir, intravenous (i.v.) vincristine, prednisone, and i.v.
      daunorubicin. The vincristine (2 mg in 10 mL diluent) was inadvertently injected
      into her Ommaya reservoir. Within 10 minutes, the error was realized. Despite
      optimal care, nausea and vomiting developed the first night, followed
      sequentially by coarse tremor, disorientation, horizontal nystagmus, and stupor.
      Her mental status waxed and waned until day 9, at which time she became
      responsive only to noxious stimuli. By day 11, she was deeply comatose and on day
      40 she died without regaining any neurological function. CONCLUSION: Despite
      aggressive and immediate therapy, intraventricular vincristine infusion produced
      neurologic toxicity, with progressive loss of mental function, followed by coma
      and death. Systems need to be developed to prevent inadvertent central nervous
      system administrations.

PMID- 9656983
TI  - ECG changes and plasma concentrations of propafenone and its metabolites in a
      case of severe poisoning.
AB  - CASE REPORT: Propafenone is a class IC antiarrhythmic agent metabolized into two
      major metabolites, 5-hydroxypropafenone and N-depropylpropafenone. The potency of
      5-hydroxypropafenone to block fast sodium channels is comparable to that of its
      parent. We report the positive correlation between plasma concentrations and
      electrocardiographic changes in a patient with severe oral self-poisoning. Serial
      ECG changes were measured and plasma concentrations were determined by high
      performance liquid chromatography. The initial plasma concentrations of
      propafenone were in the toxic range and correlated with the widening of the QRS
      complex. The slow decline in concentration during this first phase might relate
      to saturation of the isoenzyme CYP2D6. The half-life of propafenone, calculated
      from the second phase, was approximately 3 hours, defining the patient as a fast
      metabolizer. The initial concentrations of the metabolite N-depropylpropafenone
      were surprisingly higher than those of 5-hydroxypropafenone which may also be due
      to saturation of CYP2D6.

PMID- 9656984
TI  - Acute cerebral gas embolism from hydrogen peroxide ingestion successfully treated
      with hyperbaric oxygen.
AB  - CASE REPORT: We present a case of an adult who suffered an apparent stroke
      shortly after an accidental ingestion of concentrated hydrogen peroxide. Complete
      neurologic recovery occurred quickly with hyperbaric therapy. Hydrogen peroxide
      can produce acute gas embolism. Hyperbaric therapy is the definitive treatment
      for gas embolism from hydrogen peroxide ingestion as it is for all other causes
      of acute gas embolism. This is the first case reported in the literature of
      hyperbaric therapy used successfully to treat cerebral gas embolism caused by
      hydrogen peroxide.

PMID- 9656985
TI  - Possible serotonin syndrome from paroxetine and clonazepam.

PMID- 9656986
TI  - Getting to the root (Acorus calamus) of the problem.

PMID- 9656987
TI  - Liver injury after contrast-enhanced, computed tomography with iopromide.

PMID- 9656988
TI  - Regulatory and safety issues regarding special nutritional products.

PMID- 9656989
TI  - Nuclear import and export of viruses and virus genomes.
AB  - Many viruses replicate in the nucleus of their animal and plant host cells.
      Nuclear import, export, and nucleo-cytoplasmic shuttling play a central role in
      their replication cycle. Although the trafficking of individual virus proteins
      into and out of the nucleus has been well studied for some virus systems, the
      nuclear transport of larger entities such as viral genomes and capsids has only
      recently become a subject of molecular analysis. In this review, the general
      concepts emerging are discussed and a survey is provided of current information
      on both plant and animal viruses. Summarizing the main findings in this emerging
      field, it is evident that most viruses that enter or exit the nucleus take
      advantage of the cell's nuclear import and export machinery. With a few
      exceptions, viruses seem to cross the nuclear envelope through the nuclear pore
      complexes, making use of cellular nuclear import and export signals, receptors,
      and transport factors. In many cases, they capitalize on subtle control systems
      such as phosphorylation that regulate traffic of cellular components into and out
      of the nucleus. The large size of viral capsids and their composition (they
      contain large RNA and DNA molecules for which there are few precedents in normal
      nuclear transport) make the processes unique and complicated. Prior capsid
      disassembly (or deformation) is required before entry of viral genomes and
      accessory proteins can occur through nuclear pores. Capsids of different virus
      families display diverse uncoating programs which culminate in genome transfer
      through the nuclear pores.

PMID- 9656990
TI  - Suppression of antigen-specific T cell proliferation by measles virus infection:
      role of a soluble factor in suppression.
AB  - Measles virus infection causes a profound immunosuppression. The basis for this
      immunosuppression is not known. This immunosuppression could be due to virus
      acting directly on lymphoid cells, the production of an immunosuppressive viral
      product, or a lymphoid product. We have developed an antigen-specific T cell
      system to study measles virus-T-cell interactions. We demonstrate that as few as
      five infectious viral particles added to 1000 T cells results in profound
      inhibition of antigen-specific T cell proliferation. Supernates taken from
      measles virus-infected T cells suppress the proliferation of uninfected T cells.
      Measles-virus-infected HeLa or Vero cells do not produce the factor. The
      antiproliferative effects of the supernates cannot be attributed to infectious
      virus, IL-10 or TGF-beta. The soluble factor appears to be larger than 100 kDa,
      yet retains antiproliferative activity following trypsin digestion with a size
      less than 10 kDa. Loss of activity is seen following heat treatment at 56 degrees
      C. The factor is lymphoid cell specific and exhibits cytokine-like behavior yet
      appears not to be a known cytokine. This soluble factor may be responsible for
      the overt clinical immunosuppression seen in man and a previously undescribed
      cytokine induced by measles virus infection of human lymphocytes.

PMID- 9656991
TI  - The 105-kDa polyprotein of southern bean mosaic virus is translated by scanning
      ribosomes.
AB  - The cowpea strain of southern bean mosaic virus (SBMV-C) is a positive-sense RNA
      virus. Three open reading frames (ORF-1, ORF2, and ORF3) are expressed from the
      genomic RNA. The ORF1 and ORF2 initiation codons are located at nucleotide (nt)
      positions 49 and 570, respectively. ORF1 is expressed by a 5' end-dependent
      scanning mechanism, but it is not known how ribosomes gain access to the ORF2
      initiation codon. In experiments described here, it was demonstrated that the
      translation of ORF2 was sensitive to cap analog in a cell-free extract. In vitro
      and in vivo studies showed that the addition of one or more AUG codons between
      the 5' end of the SBMV-C RNA and the ORF2 initiation codon reduced ORF2
      expression and that elimination of the ORF1 initiation codon increased ORF2
      expression. Altering the sequence context of the ORF1 initiation codon to one
      more favorable for translation initiation also reduced ORF2 expression in vivo.
      Nucleotide deletions and insertions between SBMV-C nt 218-520 did not abolish
      ORF2 expression. In most cases, these mutations resulted in reduced expression of
      both ORF1 and ORF2. These results are consistent with translation of ORF2 by
      leaky scanning.

PMID- 9656992
TI  - Nef proteins of distinct HIV-1 or -2 isolates differ in their binding properties
      for HCK: isolation of a novel Nef binding factor with characteristics of an
      adaptor protein.
AB  - The Nef gene of the human and simian immunodeficiency viruses HIV and SIV has
      been implicated in pathogenicity; however, the mechanism by which Nef induces
      disease is still unknown. An impact on signal transduction in cells has been
      suggested by the interaction of Nef from an HIV-1 strain and tyrosine kinases
      like HCK and LCK as well as serine/threonine kinases. We have confirmed the
      binding of HCK to HIV-1 subtype B Nef and demonstrated an equally strong
      interaction with a subtype E Nef protein but weaker binding to Nef of HIV-2
      subtype A (HIV-2D194). No binding, however, was observed to HIV-2 subtype B Nef
      (HIV-2D205). Instead, this protein bound to a novel cellular protein, Nefin 1,
      with characteristics of an adaptor protein and strong expression in all human
      hematopoietic tissues. Nefin 1 binds through an amino-terminal domain, which is
      related to SH3 domains. For interaction of Nef with Nefin 1, the PxxP motif and
      the three-dimensional conformation of the molecule appear necessary. In
      conclusion, this study demonstrates that Nef proteins of divergent strains of HIV
      1 and HIV-2 may use different elements of signal transduction pathways for the
      induction of pathogenicity in vivo.

PMID- 9656993
TI  - Shared antigenic epitopes on the V3 loop of HIV-1 gp120 and proteins on activated
      human T cells.
AB  - Proliferation of HIV-1 in the infected host is characterized by a progressive
      loss of CD4+ T lymphocytes and consequent dysregulation of the immune system.
      Both direct and indirect mechanisms have been proposed. We show here that
      proteins with molecular weights 35, 48, and 110 kDa on stimulated primary human T
      cells are recognized by neutralizing antibodies against the V3 loop of HIV-1
      gp120. Recognition is specific since it can be blocked by a recombinant HIV-1
      gp120. Furthermore, these V3 monoclonal antibodies, as well as sera from AIDS
      patients that recognized these V3-like proteins, induced killing of HIV-1
      infected as well as uninfected T cells. This killing was also inhibited by HIV-1
      gp120 V3 peptides. These results indicate that the V3 loop shares epitopes with
      proteins on stimulated T cells. This may be an additional autoimmune mechanism
      contributing to CD4+ T cell disappearance in AIDS. V3 antibodies have been
      proposed as potential prophylactic agents. However, if such vaccines were based
      on certain epitopes, they might induce cross-reacting immune responses with
      cellular proteins. Vaccine candidates should be evaluated for such potential
      effects.

PMID- 9656994
TI  - The structural gene module in Streptococcus thermophilus bacteriophage phi Sfi11
      shows a hierarchy of relatedness to Siphoviridae from a wide range of bacterial
      hosts.
AB  - The structural gene cluster and the lysis module from lytic group II
      Streptococcus thermophilus bacteriophage phi Sfi11 was compared to the
      corresponding region from other Siphoviridae. The analysis revealed a hierarchy
      of relatedness. phi Sfi11 differed from the temperate S. thermophilus
      bacteriophage phi O1205 by about 10% at the nucleotide level. The majority of the
      changes were point mutations, mainly at the third base position. Only a single
      gene (orf 695) differed substantially between the two phages. Over the putative
      minor tail and lysis genes, phi Sfi11 and the lytic group 1 S. thermophilus phi
      Sfi19 shared regions with variable degrees of similarity. Orf 1291 from phi Sfi19
      was replaced by four genes in phi Sfi11, two of which (orf 1000 and orf 695)
      showed a complicated pattern of similarity and nonsimilarity compared with phi
      Sfi19. The predicted orf 695 gp resembles the receptor-recognizing protein of T
      even coliphages in its organization, but not its sequence. No sequence similarity
      was detected between phi Sfi11 and phi Sfi19 in the region covering the major
      head and tail genes. Comparison of the structural gene map of phi Sfi11 with that
      of Siphoviridae from gram-positive and -negative bacterial hosts revealed a
      common genomic organization. Sequence similarity was only found between phi Sfi11
      and Siphoviridae from gram-positive hosts and correlated with the evolutionary
      distance between the bacterial hosts. Our data are compatible with the hypothesis
      that the structural gene operon from Siphoviridae of the low G + C group of gram
      positive bacteria is derived from a common ancestor.

PMID- 9656995
TI  - Proteolytic processing of rubella virus nonstructural proteins.
AB  - The genomic RNA of rubella virus contains two long open reading frames (ORF), a
      5'-proximal ORF that codes for the nonstructural proteins and a 3'-proximal ORF
      that encodes the structural proteins. The cDNA encoding the nonstructural protein
      ORF of the wild-type M33 strain of rubella virus has been obtained and sequenced.
      Comparison between the nonstructural proteins of the M33 and Therien strains of
      rubella virus revealed a 98% homology in nucleotide sequence and 98.1% in deduced
      amino acid sequence. To examine the processing of rubella virus nonstructural
      protein, the complete nonstructural protein ORF was expressed in BHK cells using
      a pSFV expression vector. Three nonstructural protein products (p200, p150, and
      p90) with molecular weights of 200, 150, and 90 kDa were identified using
      antisera raised against synthetic peptides corresponding to regions of the
      nonstructural proteins. p200 is the polyprotein precursor, while p150 and p90 are
      the cleavage products. Site-directed mutagenesis of the Cys-1151 residue (one of
      the catalytic dyad residues of the viral protease) and of the Gly-1300 residue
      (the viral protease cleavage site) abrogated protease activity and p200 precursor
      cleavage, respectively. Coexpression of mutant constructs in BHK cells indicated
      that rubella virus protease can function both in cis and in trans.

PMID- 9656996
TI  - Membrane-anchored incorporation of a foreign protein in recombinant influenza
      virions.
AB  - The RNA polymerase I system for in vivo synthesis of recombinant influenza vRNA
      molecules was used for the expression of a chimeric protein, consisting of the
      341-amino-acid ectodomain of the glycoprotein E2 of classical swine fever virus
      and the 37-amino-acid C-terminal membrane anchor of the influenza virus
      hemagglutinin (HA). During infection with an influenza A helper virus the
      amplified pseudo-viral RNA was packaged into progeny virions together with
      influenza vRNA segments. The foreign fusion protein E2-HA was shown to be
      physically incorporated into the viral envelope. Incorporation of a third major
      glycoprotein into the envelope did not affect biological functions of HA and
      neuraminidase that are required for the generation of infectious virus particles.
      Based on mutational analyses of the cytoplasmic tail of E2-HA fusion proteins
      three modes of interaction during virus budding have been observed: nonspecific
      low-level incorporation (truncated tails), specific full-level incorporation
      (wild-type amino acid sequence or minor variations of it), and exclusion from
      incorporation (elongated tails).

PMID- 9656997
TI  - The interaction of neuraminidase and hemagglutinin mutations in influenza virus
      in resistance to 4-guanidino-Neu5Ac2en.
AB  - We have previously described a 4-guanidino-Neu5Ac2en (zanamivir)-resistant
      neuraminidase (NA) variant G70C4-G, with an active site mutation Glu 119 to Gly.
      This variant has been found to also harbor a hemagglutinin (HA) mutation in the
      receptor binding site, Ser 186 to Phe. Examination of early passages of the G70C4
      G virus revealed that this HA mutation had arisen by the first passage. From a
      subsequent passage two transient variants were isolated which had each acquired a
      different second HA mutation, Ser 165 to Asn and Lys 222 to Thr. Both were highly
      drug resistant and drug dependent and their ability to adsorb to and penetrate
      cells was decreased. Comparison of drug sensitivities between the variant, with
      the additional HA mutation at Ser 165, and viruses with either mutation alone
      revealed that these two HA mutations acted synergistically to increase
      resistance. To determine the contribution to resistance of each of the NA and HA
      mutations in G70C4-G, the NA mutation was separated from the HA mutation by
      reassorting. The NA mutation and the HA mutation each conferred low-level
      resistance to zanamivir, while the two mutations interacted synergistically in
      the double mutant to give higher resistance in vitro. Infectivity was not
      adversely affected in the double mutant and while there was a small decrease in
      sensitivity to zanamivir in the mouse model, there was no detectable resistance
      to zanamivir in the ferret model.

PMID- 9656998
TI  - Critical point mutations for hepatitis C virus NS3 proteinase.
AB  - The hepatitis C virus NS3 proteinase plays an essential role in processing of HCV
      nonstructural precursor polyprotein. To detect its processing activity, we
      developed a simple trans-cleavage assay. Two recombinant plasmids expressing the
      NS3 proteinase region and a chimeric substrate polyprotein containing the NS5A/5B
      cleavage site between maltose binding protein and protein A were co-introduced
      into Escherichia coli cells. The proteinase processed the substrate at the single
      site during their polyprotein expression. Deletion analysis indicated that the
      functionally minimal domain of the NS3 proteinase was composed of 146 amino
      acids, 1059 to 1204. We isolated several cDNA clones encoding the functional
      domain of the NS3 proteinase from the sera of patients chronically infected with
      HCV and determined their proteinase activity by this trans-cleavage assay. Both
      active and inactive clones existed in the same patients. Comparative sequence
      analyses of these clones suggested that certain point mutations seemed to be
      related to the loss of proteolytic activity. This was confirmed by back mutation
      experiments. Among the critical mutations, Pro-1168 to Thr and Arg-1135 to Gly
      were intriguing. These amino acids, which are situated near the oxyanion hole,
      seem to be essential for maintaining the conformation of the active center of the
      NS3 proteinase.

PMID- 9656999
TI  - Primary SIVsm isolates use the CCR5 coreceptor from sooty mangabeys naturally
      infected in west Africa: a comparison of coreceptor usage of primary SIVsm, HIV
      2, and SIVmac.
AB  - Genetically divergent strains of simian immunodeficiency virus (SIV) from
      macaques (mac), chimpanzees, and sooty mangabeys (SM) efficiently used rhesus and
      human CCR5 (R5), but not CXCR4 (xR4), for cell entry. Thus far, however, no
      studies have characterized primary SIVsm strains for their use of coreceptors
      derived from their own natural host. Coreceptor usage of two primary, blood
      derived SIVsm isolates, SIVsmSL92b and SIVsmFNS from naturally infected sooty
      mangabeys, was determined. Primary SIVsm efficiently used SM-CCR5 expressed on
      HOS.CD4 and U87.CD4 cells. Sequence polymorphisms in CCR5 found in four sooty
      mangabeys did not alter viral entry. Unlike primary rhesus blood-derived R5
      tropic SIVmac251, primary SM blood-derived R5-tropic SIVsm was strongly CD4
      dependent. The SM-CXCR4 gene was fully functional for xR4-tropic primate
      lentiviruses, but was not used by primary SIVsm. Therefore, the lack of xR4
      tropism among naturally occurring SIVsm strains was not due to CxCR4 gene defects
      in the natural host. SIVmac derived from four macaques with AIDS also did not use
      macaque- or SM-derived CXCR4, showing that xR4 tropism did not develop during
      progression to disease as for humans infected with HIV-1. Three of four primary
      HIV-2 strains used CCR5 from human, sooty mangabey, and macaque. The fourth, HIV
      27924A, obtained from a patient with AIDS, was xR4-tropic. Because SIVmac is most
      closely related to HIV-2, SIVmac might be expected to rnimic tropisms of HIV-2
      infections. However, the correlation between xR4 tropism and AIDS may be a
      species-specific phenomenon limited to humans. The R5-tropic primary SIVsm and
      HIV-2 strains grew in CCR5-negative human PBMC, consistent with their use of non
      CCR5 coreceptors. However, primary SIVsmSL92b did not use non-CCR5 coreceptors
      efficiently. The two primary SIVsm isolates replicated poorly in CEMx174 cells,
      which do not express CCR5, compared to CCR5-positive PM1 cells. SIVmac grew
      equally well in both cell lines. The findings show that SM-chemokine receptors
      are fully functional for virus entry and that multicoreceptor tropism is a common
      property of primary lentiviruses within the SIVsm/HIV-2 subfamily.

PMID- 9657000
TI  - Characterization of Toscana virus-defective interfering particles generated in
      vivo.
AB  - Toscana (TOS) virus stocks strongly interfering with standard virus replication
      were obtained by sequential passages of virus in suckling mouse brain.
      Characterization of viral RNAs in these stocks showed the presence of a
      heterogeneous population of defective RNA molecules derived from the L genomic
      segment, in both nucleocapsid (NC) and messenger RNAs, suggesting that these
      molecules could be replicated, assembled, and transcribed. Subgenomic RNAs from
      the L segment but not from the S or M segments were found in cells infected with
      these stocks. Defective RNA molecules interfered with virus replication and
      retained 5' and 3' genomic termini. Nucleotide sequence analysis of some cloned
      defective interfering (DI) RNAs revealed they contained one or more internal
      deletions reducing their length to 7-13% of the full-length L segment. An
      identical sequence motif, of variable length, was found at both terminal sites of
      the RNA junction on standard L sequences. This motif was retained only in one
      copy in the subgenomic RNA. These results are consistent with the generation of
      TOS virus DI particles in vivo and suggest that the defective genomic RNAs could
      be generated by polymerase jumping from a sequence to an identical one spatially
      closed because of the RNA structure.

PMID- 9657001
TI  - DNA vaccines expressing either the GP or NP genes of Ebola virus protect mice
      from lethal challenge.
AB  - DNA vaccines expressing the envelope glycoprotein (GP) or nucleocapsid protein
      (NP) genes of Ebola virus were evaluated in adult, immunocompetent mice. The
      vaccines were delivered into the skin by particle bombardment of DNA-coated gold
      beads with the Powderject-XR gene gun. Both vaccines elicited antibody responses
      as measured by ELISA and elicited cytotoxic T cell responses as measured by
      chromium release assays. From one to four vaccinations with 0.5 microgram of the
      GP DNA vaccine resulted in a dose-dependent protection from Ebola virus
      challenge. Maximal protection (78% survival) was achieved after four
      vaccinations. Mice were completely protected with a priming dose of 0.5 microgram
      of GP DNA followed by three or four subsequent vaccinations with 1.5 micrograms
      of DNA. Partial protection could be observed for at least 9 months after three
      immunizations with 0.5 microgram of the GP DNA vaccine. Comparing the GP and NP
      vaccines indicated that approximately the same level of protection could be
      achieved with either vaccine.

PMID- 9657002
TI  - Functional modules important for activated expression of early genes of herpes
      simplex virus type 1 are clustered upstream of the TATA box.
AB  - Functional analysis of two promoters controlling early herpes simplex virus type
      1 (HSV-1) transcripts encoding the UL37 and UL50 (dUTPase) proteins are described
      in this report. Transcripts expressed under the control of these promoters were
      found to be expressed early regardless of the position of the transcription unit
      within the viral genome. Despite this, wt dUTPase mRNA was 6-10 times more
      abundant than the UL37 transcript both in wt and recombinant viruses. This same
      difference in transcript abundance was seen when a reporter gene (beta
      galactosidase) was controlled by the two promoters in recombinant viruses in the
      heterologous glycoprotein C (gC) locus. Thus, both the kinetics and relative
      abundance of UL50 and UL37 transcripts are a direct function of their respective
      promoter regulatory elements. Characterization of mutated UL37 and UL50 promoters
      in recombinant viruses showed that the functional modules important for
      expression from these promoters are concentrated upstream of the transcription
      start site; however the extent and composition of these modules in terms of the
      cis-acting elements they contain was different for each. For the UL37 promoter,
      both a HiNF-P factor binding site (-53 to -58 bp) and the TATA homology (-22 to 
      27) were required for any detectable expression, while an Sp1 binding site at 
      123 augmented this but was not absolutely required. In contrast, the only
      functional elements crucial for expression from the UL50 promoter were the TATA
      box (-25 to -31) and an Sp1 binding site at -117 bp relative to the cap site.
      Despite differences in detail, when the functional architecture of these two
      early promoters were compared to the extensively characterized HSV-1 thymidine
      kinase (UL23) promoter, class-specific similarities are clearly apparent.

PMID- 9657003
TI  - Evolutionary relationships among putative RNA-dependent RNA polymerases encoded
      by a mitochondrial virus-like RNA in the Dutch elm disease fungus, Ophiostoma
      novo-ulmi, by other viruses and virus-like RNAs and by the Arabidopsis
      mitochondrial genome.
AB  - The nucleotide sequence (2617 nucleotides) of virus-like double-stranded (ds) RNA
      3a in a diseased isolate, Log1/3-8d2 (Ld), of the ascomycete fungus Ophiostoma
      novo-ulmi has been determined. One strand of the dsRNA contains an open reading
      frame (ORF) with the potential to encode a protein of 718 amino acids, and the
      complementary strand contains two smaller ORFs with the potential to encode
      proteins of 178 and 182 amino acids, respectively. The large ORF contains 12 UGA
      codons which code for tryptophan in ascomycete mitochondria and has a codon bias
      typical of mitochondrial genes, consistent with the localization of Ld dsRNAs
      within the mitochondria. The amino acid sequence contains motifs characteristic
      of RNA-dependent RNA polymerases (RdRps). This putative RdRp was shown to be
      related to putative RdRps of mitochondrial dsRNAs of another ascomycete and a
      basidiomycete fungus and also to a putative RdRp encoded by the mitochondrial
      genome of Arabidopsis thaliana. In multiple sequence alignments, the fungal
      mitochondrial dsRNA-encoded RdRp-like proteins formed a cluster, ancestrally
      related to the RdRps of the yeast 20S and 23S RNA replicons and of the positive
      stranded RNA bacteriophages of the Leviviridae family, but distinct from RdRps of
      other families and genera of fungal RNA viruses and related plant and animal RNA
      viruses. Northern blot analysis with RNA 3a strand-specific probes indicated that
      nucleic acid extracts of Ld contain more single-stranded (positive-stranded) RNA
      than dsRNA, consistent with an evolutionary relationship between RNA 3a and
      positive-stranded RNA phages.

PMID- 9657004
TI  - Transfer RNA mimicry in a new group of positive-strand RNA plant viruses, the
      furoviruses: differential aminoacylation between the RNA components of one
      genome.
AB  - Recent sequencing of the genomes of several furoviruses--fungus-transmitted rod
      shaped positive-strand plant viruses--has suggested the presence of tRNA-like
      structures (TLSs) at the 3' ends of the genomic RNAs. We show here that the
      genomic RNAs of soil-borne wheat mosaic virus (SBWMV), beet soil-borne virus
      (BSBV), potato mop-top virus (PMTV), peanut clump virus (PCV), and Indian peanut
      clump virus (IPCV) all possess functional TLSs that are capable of high
      efficiency valylation. While the SBWMV, BSBV, and PMTV TLSs are similar to those
      found in tymoviruses, the PCV and IPCV TLSs harbor an insertion of about 40
      nucleotides between the two halves of the TLS. The valylated SBWMV and BSBV RNAs
      formed tight complexes with wheat germ EF-1 alpha.GTP (Kd = 2 to 11 nM), whereas
      valylated PMTV, PCV, and IPCV RNAs bound EF-1 alpha.GTP weakly (Kd > or = 50 nM).
      The TLS of PCV RNA2 differs from PCV RNA1 in lacking the major valine identity
      nucleotide in the anticodon and consequently is capable of only very inefficient
      valylation. This is the first case of differential aminoacylation between the RNA
      components of one genome.

PMID- 9657005
TI  - A cell surface protein with herpesvirus entry activity (HveB) confers
      susceptibility to infection by mutants of herpes simplex virus type 1, herpes
      simplex virus type 2, and pseudorabies virus.
AB  - Certain mutant strains of herpes simplex virus type 1 (HSV-1) are unable to
      infect cells in which entry is dependent on HVEM, the previously described
      herpesvirus entry mediator designated here as herpesvirus entry protein A (HveA).
      These mutant viruses can infect other cells where entry is apparently dependent
      on other co-receptors. The mutant virus HSV-1(KOS)Rid1 was used to screen a human
      cDNA expression library for ability of transfected plasmids to convert resistant
      Chinese hamster ovary cells to susceptibility to virus entry. A plasmid
      expressing the previously described poliovirus receptor-related protein 2 (Prr2)
      was isolated on the basis of this activity. This protein, designated here as
      HveB, was shown to mediate the entry of three mutant HSV-1 strains that cannot
      use HVEM as co-receptor, but not wild-type HSV-1 strains. HveB also mediated the
      entry of HSV-2 and pseudorabies virus but not bovine herpesvirus type 1. HveB was
      expressed in some human neuronal cell lines, fibroblastic cells, keratinocytes,
      and primary activated T lymphocytes. Antibodies specific for HveB blocked
      infection of HveB-expressing CHO cells and a human fibroblastic cell strain
      HEL299. Differences in ability of HSV-1 and HSV-2 strains to use HveB for entry
      should influence the types of cells that can be infected and thereby account in
      part for serotype and strain differences in tissue tropism and pathogenicity.

PMID- 9657006
TI  - Nucleotide sequence of Bombyx mori cytoplasmic polyhedrosis virus segment 8.
AB  - The segments 8 (S8) of the 10 double-stranded RNA genomes from Bombyx mori
      cytoplasmic polyhedrosis virus (BmCPV) strains I and H were converted into cDNAs,
      amplified by PCR, and cloned. The nucleotide sequence analysis of the two full
      length S8 cDNAs showed that the segments consist of 1328 nucleotides encoding
      putative proteins (p44) of 390 amino acids with molecular masses of about 44 kDa,
      which have glutamic acid-rich and proline-rich domains in their central regions.
      They had quite high identity with each other: about 98% in nucleotide and amino
      acid sequences. The recombinant p44 expressed in BmN4 cells using the baculovirus
      vector was detected by immunoblot analysis. p44 was also confirmed with the same
      antiserum to be present in BmCPV-infected midgut cells, but not in polyhedra,
      virus virions and uninfected midgut cells, indicating that p44 is expressed as a
      nonstructural protein of BmCPV.

PMID- 9657007
TI  - Genetic alterations in early stage adenocarcinoma of the lung.

PMID- 9657008
TI  - Analysis of loss of heterozygosity in small adenocarcinomas of the lung.
AB  - BACKGROUND: Despite the many studies of genetic alterations in advanced lung
      carcinomas, few reports have analyzed early stage adenocarcinoma of the lung.
      METHODS: We focused on small pulmonary adenocarcinomas, classified according to
      recently proposed histological criteria (Noguchi M., et al. Cancer 1995;75:2844
      52) which divided adenocarcinomas 2 cm or less in diameter into two groups; one
      showing replacing growth of the pulmonary alveolar structure [A, localized
      bronchioloalveolar carcinoma (LBAC); B, LBAC with alveolar collapse; C, LBAC with
      active fibroblastic proliferation] and the other showing non-replacing growth (D,
      poorly differentiated adenocarcinoma). Ninety-four small pulmonary
      adenocarcinomas, including 40 of type A and B, 30 of type C and 24 of type D,
      were examined for loss of heterozygosity (LOH) using microsatellite markers.
      RESULTS: The frequencies of LOH were 19.8% in types A and B, 26.8% in type C and
      32.7% in type D tumors. There were no significant differences in the frequency of
      LOH on chromosomes 2p, 3p, 9p and 17q among tumor types. However, on 17p, the
      frequency of LOH was significantly lower for types A and B than for type C or D.
      Three out of six type C tumors which were positive for LOH at several loci showed
      different LOH patterns in two areas (central and peripheral regions).
      CONCLUSIONS: Allelic losses were detected in very early adenocarcinomas and the
      frequency of LOHs on chromosome 17p increased during malignant progression of the
      tumor. Heterogeneous genetic alterations were demonstrated even in small
      pulmonary adenocarcinomas.

PMID- 9657009
TI  - Diagnosis and treatment of malignant lymphoma of the parotid gland.
AB  - BACKGROUND: To correlate the imaging and pathological features and to discuss
      therapeutic modalities and the prognosis of malignant lymphoma originating in the
      parotid gland, which is relatively rare. METHODS: The subjects were five patients
      with malignant lymphoma originating in the parotid gland. Three and two patients
      were stage I and stage II, respectively. CT examination was applied to all,
      whereas only one case was examined by MRI. All were treated with radiotherapy
      following surgery or chemotherapy. Three patients underwent combination
      chemotherapy, such as with MACOP-P or VEPA, following surgery. RESULTS: Although
      malignant lymphoma originating in the parotid gland is histologically described
      as low-grade non-Hodgkin's lymphoma, two and one of the cases were classified as
      intermediate and high grade in the present series, respectively. These three
      exhibited a tendency for infiltration into the adjacent tissue and tumor
      inhomogeneity in the imaging findings, suggesting a correlation with
      histologically intermediate or high-grade non-Hodgkin's lymphoma. It was
      successfully controlled by radiotherapy, with dosages ranging from 40 to 44 Gy.
      The patients were followed for 2-8 years. No relapse was found in the three
      patients with stage I. However, both stage II patients had relapses and were
      subjected to additional radiotherapy combined with chemotherapy. Since then, no
      tumor relapse has been noted at either this or other sites. CONCLUSIONS:
      Malignant lymphoma including intermediate or high grade originating in the
      parotid gland indicated satisfactory prognosis following radiotherapy and
      chemotherapy.

PMID- 9657010
TI  - Cyclophosphamide, adriamycin, 5-fluorouracil and high-dose toremifene for
      patients with advanced/recurrent breast cancer. The Japan Toremifene Cooperative
      Study Group.
AB  - BACKGROUND: Multi-combination chemotherapy consisting of anthracyclines has been
      effective but has not invariably prolonged the survival period in
      advanced/recurrent breast cancer. The possibility has been discussed that
      chemoendocrine therapy combined with endocrine agents is more effective. METHODS:
      In order to evaluate the toxicity and efficacy of a new endocrine therapy for
      advanced/recurrent breast cancer, we ran a pilot study during the period from
      July 1994 to July 1996. RESULTS: Twenty-two patients with advanced/recurrent
      breast cancer were treated with chemoendocrine therapy consisting of
      cyclophosphamide (100 mg/body) p.o. daily for 14 days, with adriamycin (40 mg/m2)
      i.v. and 5-fluorouracil (500 mg/body) i.v. on day 1 (repeated every 3 weeks for 9
      weeks) (CAF therapy), and high-dose toremifene (120 mg/body) p.o. daily. Of 20
      evaluable patients, two showed complete response (10%), eight partial response
      (40%), six no change (30%) and four progressive disease (20%). The overall
      response rate was 50%, and the median duration of response was 69.5 days (28-133+
      days). The major toxicities were drug-induced alopecia, gastrointestinal toxicity
      and hematological toxicity, but these were clinically well tolerated. No serious
      cardiac, liver or renal symptom was seen. CONCLUSIONS: Based on these results, we
      consider the addition of high-dose toremifene to the CAF therapy to be useful in
      the treatment of advanced and recurrent breast cancer.

PMID- 9657011
TI  - Nonfunctioning islet cell tumors of the pancreas: clinical, imaging and
      pathological aspects in 16 patients.
AB  - BACKGROUND: Nonfunctioning islet cell tumors (NFICTs) usually reach a large size
      prior to detection, at which stage patients have some symptoms or signs.
      Recently, NFICTs have been discovered in asymptomatic patients with increasing
      frequency owing to advances in diagnostic imaging techniques. This study
      investigated clinical, imaging and pathological features in recent cases of
      NFICT. METHODS: The medical records, radiographs and pathological specimens of 16
      patients with NFICT who were evaluated between April 1991 and March 1996 were
      reviewed. RESULTS: Tumor sizes ranged from 0.8 to 17 cm (average, 5.2 cm). Five
      patients (31%) had some symptoms or signs at the time of diagnosis; however, the
      other 11 (69%) had no symptoms. Of 10 patients with a tumor of size 5 cm or less,
      nine were asymptomatic and all tumors were histologically benign. In contrast, in
      six patients with a tumor larger than 5 cm, four had some symptoms and five
      tumors were malignant. The detection rates of pancreatic tumor mass on
      ultrasonography and computed tomography were 94% (15/16) each. All 14 patients in
      whom the tumor was completely resected survived without recurrence; however, the
      remaining two patients with liver metastases died following recurrence.
      CONCLUSIONS: US and CT are useful in detecting NFICTs even if the tumor is small
      and the patient is asymptomatic. The detection of NFICTs of small size and their
      complete removal are essential for a successful cure.

PMID- 9657012
TI  - Adjunctive value of cell proliferation but not of apoptosis to interpret
      pathologic effects on prostatic cancer after neoadjuvant endocrine therapy.
AB  - BACKGROUND: The current histological evaluation of the effects of endocrine
      therapy has difficulty in distinguishing pathologic degeneration caused by
      androgen ablation from residual poorly differentiated tumor. Therefore, we
      examined the changes in cell proliferation and apoptosis before and after
      endocrine therapy and analyzed whether they correlated with pathologic effects
      and histological differentiation. METHODS: Between January 1986 and December
      1995, 52 patients with clinical stage B2 and C prostate cancer underwent radical
      prostatectomy after neoadjuvant endocrine therapy (median duration 3.8 months).
      Proliferative and apoptotic activities of pretreatment biopsy specimens and
      radical prostatectomy specimens were analyzed with MIB-1 monoclonal antibody and
      in situ end-labeling of fragmented DNA. RESULTS: The mean proliferative index
      (PI) of radical prostatectomy specimens was significantly lower than that of
      biopsy specimens (P = 0.000003) and the decrease in PI after endocrine therapy
      was significantly related to histological differentiation (P = 0.014). There was
      a weak relationship between the decrease in PI after endocrine therapy and
      pathologic effects (P = 0.054), while in pathologically effective cases (Grades 2
      and 3), three out of 16 (19%) showed a < 50% decrease in PI after endocrine
      therapy, and may be regarded as having poorly differentiated tumors. The mean
      apoptotic index (AI) of prostatectomy specimens tended to be higher than that of
      biopsy specimens (P = 0.054). The increase in AI after endocrine therapy was not
      related to histological differentiation and pathologic effects. CONCLUSION:
      Pathologic effects caused by endocrine therapy may be in part misled by routine
      histopathologic staining and the change in PI may help in recognizing the
      pathologic effects of endocrine therapy and have adjunctive value for the
      interpretation of the effects of endocrine therapy.

PMID- 9657013
TI  - Splenic irradiation for prolymphocytic leukemia: is it preferable as an initial
      treatment or not?
AB  - We describe a case of B-cell prolymphocytic leukemia (PLL) successfully treated
      with splenic irradiation (SI). A 69-year-old woman was admitted to our hospital
      because of massive splenomegaly and leukocytosis. Peripheral blood showed
      hemoglobin (Hb) 7.4 g/dl, platelets 48 x 10(9)/l and white blood cells (WBC) 50.3
      x 10(9)/l with 90% prolymphocytes. Bone marrow was hypercellular with 60%
      prolymphocytes. Surface marker analysis revealed that prolymphocytes were
      positive for CD20, CD22, FMC7, HLA-DR and surface immunoglobulin (mu, delta and
      lambda), but negative for CD5 and mouse erythrocyte rosette. A diagnosis of B
      cell PLL was made. SI (1.5 Gy x 4/week, total dose 19.5 Gy) was chosen for the
      treatment and a remarkable response was achieved immediately after the first
      irradiation. Finally, a single course of SI induced complete remission without
      any significant side effect. One year after the SI, she showed no splenomegaly
      and almost normal peripheral blood cell count (Hb 11.2 g/dl, platelets 100 x
      10(9)/l, WBC 3.6 x 10(9)/l with 71% neutrophils and no prolymphocyte). She has
      been well for more than 24 months. This case showed that SI may remain valuable
      for an initial course of PLL treatment.

PMID- 9657014
TI  - Successful treatment by radiation and hormone therapy of isolated local
      recurrence of breast cancer 24 years after mastectomy accompanied by immune
      thrombocytopenia: a case report.
AB  - We report a case of isolated local recurrence of breast cancer, which was
      accompanied by idiopathic thrombocytopenic purpura (ITP) and benign monoclonal
      gammopathy that presented 24 years after the patient underwent mastectomy. A 72
      year-old female patient with a chest wall tumor was referred to our hospital in
      November 1994. Twenty-four years previously she had surgically treated breast
      cancer, of which the pathology was scirrhous carcinoma. Needle biopsy of the
      tumor revealed tubular carcinoma, which is compatible with local recurrence of
      breast cancer. She had no evidence of regional lymph node involvement or distant
      metastasis. Hematological and serological examination revealed a low platelet
      count accompanied by M-proteinemia (IgG, kappa-type) and a mild increase in
      platelet-associated IgG. She was initially treated with extensive-field chest
      wall radiation (60 Gy), followed by systemic administration of tamoxifen.
      Complete local control of isolated local recurrence (LR) was achieved after
      radiation therapy (RT) and the patient has been progression-free for more than 2
      years. Platelet count recovered gradually to a normal level after achievement of
      complete remission induced by radiation and tamoxifen. This may be the first case
      suggestive of a paraneoplastic syndrome of immune thrombocytopenia accompanied by
      local recurrence of breast cancer.

PMID- 9657015
TI  - Malignant phyllodes tumor of the breast with hypoglycemia: report of a case.
AB  - A surgically resected case of giant malignant phyllodes tumor of the breast
      associated with a hypoglycemic attack is reported. A 54-year-old woman was
      referred to our hospital with loss of consciousness and a huge chest wall tumor.
      She was diagnosed as having a malignant phyllodes tumor by core needle biopsy and
      underwent palliative simple mastectomy because lung metastasis was detected on
      computed tomography and by other imaging modalities on admission. The
      preoperative laboratory data revealed a very low fasting blood sugar level of 37
      mg/dl. After removal of the tumor, the blood sugar level gradually normalized (90
      100 mg/dl) and the plasma insulin-like growth factor-II (IGF-II) level promptly
      decreased. The IGF-II level of tumor extracts was high (2500 ng/g wet weight) and
      the majority of atypical cells stained positively for IGF-II
      immunohistochemically. These findings suggested that the patient's hypoglycemia
      was associated with IGF-II produced by a giant malignant phyllodes tumor that
      consumed glucose.

PMID- 9657016
TI  - Spontaneous regression of primary mediastinal germ cell tumor.
AB  - A case of primary mediastinal germ cell tumor, which demonstrated spontaneous
      regression, is presented. The serum human chorionic gonadotropin level was
      elevated on admission and then decreased to the normal range with decrease in the
      size of the anterior mediastinal mass. Thoracotomy was performed with artificial
      replacement by grafts between the bilateral brachiocephalic veins and the right
      atrium. Histological diagnosis of combined teratoma with seminoma was made. After
      subsequent chemotherapy, the patient has remained alive without recurrence for
      over 10 years.

PMID- 9657017
TI  - Primary liposarcoma of the stomach: a case report and a review of the literature.
AB  - Primary liposarcoma of the stomach is rare and only seven cases have been
      described in the English literature. Here we report the eighth case, which
      occurred in a 68-year-old woman who presented with repeated tarry stools and
      hematemesis. Endoscopic examination revealed a large ulcerated submucosal mass at
      the gastric angle. The patient was treated by total gastrectomy. On microscopic
      examination, the tumor showed the features of a well differentiated sclerosing
      liposarcoma. Immunohistochemically, many spindle to stellate tumor cells were
      diffusely positive for vimentin and CD34. Positivity for S-100 protein was found
      in the adipocytic component, including lipoblasts, in addition to some spindle
      shaped tumor cells. On ultrastructural examination, the spindle to stellate cells
      had features characteristic of fibroblasts. No recurrence or metastasis was seen
      during 13 months. Liposarcoma of the stomach has to be considered in the
      differential diagnosis with other submucosal lesions, such as gastric lipoma and
      gastrointestinal stromal tumor.

PMID- 9657019
TI  - [Postanesthesia allergic complications].

PMID- 9657018
TI  - Hereditary nonpolyposis colorectal cancer associated with duodenal carcinoma: a
      case report.
AB  - Hereditary nonpolyposis colorectal cancer is an autosomal, dominantly inherited
      disease, characterized by an early age of onset, right colon predominance and an
      association with various extracolorectal malignancies. We present a case of a 47
      year-old woman who met the clinical criteria for the diagnosis of hereditary
      nonpolyposis colorectal cancer from her past and family histories. She had
      undergone operations for uterine cancer (histology not confirmed) at age 35 and
      for advanced cancer of the ascending colon at age 45. Gastroendoscopy revealed a
      flat elevated lesion, 20 mm in size, with a protrusion (type IIa + Is) in the
      second portion of the duodenum in March 1996. Additionally, colonoscopy showed a
      flat elevated lesion, 30 mm in size, with an irregular and nodular surface (type
      IIa, laterally spreading tumor) in the descending colon. After the operation, the
      resected specimen of the duodenum histologically showed a well-differentiated
      adenocarcinoma associated with a tubulo-villous adenoma which had invaded the
      submucosal layer. The tumor of the colon was histologically confirmed to be a
      moderately-differentiated adenocarcinoma with submucosal invasion. A high
      frequency of replication error positivity (4/5 loci) was detected in both of the
      tumors. Reports of early cancer of the duodenum, associated with extracolorectal
      malignancies in hereditary nonpolyposis colorectal cancer, are very rare in the
      literature. Although it is difficult to determine which extracolorectal tumor
      sites should be taken into consideration by screening programs, we believe that
      careful observation by upper gastrointestinal endoscopy, which includes the
      duodenum, is necessary for patients with hereditary nonpolyposis colorectal
      cancer.

PMID- 9657020
TI  - [The beginning of anesthesia].
AB  - On October 16, 1846, the first public demonstration of etherization, at the
      Massachusetts General Hospital, Boston, illustrated the rise of Inhalational
      Anaesthesia. Pioneers were: Hickman, Wells, Morton, Davy and Long. Anaesthesia
      was considered an American invention. Thereafter, the development of new
      molecules (cocaine, hexobarbital) which can be administered by others ways
      (spinal puncture, intravenous injections) allowed new methods of anaesthesia to
      be achieved. Thus, three successive periods have illustrated the Story of
      Anaesthesia: Inhalational Anaesthesia (1844), Local Anaesthesia (1860),
      Intravenous Anaesthesia (1932).

PMID- 9657021
TI  - [Mechanism of severe, immediate reactions to iodinated contrast material].
AB  - Immediate reactions to iodinated contrast material are usually supposed to be due
      to complement activation. Histamine has not been proved responsible for signs.
      However the results described in the literature are controversial: they have been
      obtained from non-reacting patients or during minor or moderate reactions. We
      suggest to study mediator release during unexpected severe reactions and to
      perform skin tests and IgE measurements in patients with proved liberation of
      mediators.

PMID- 9657022
TI  - [Postoperative allergic complications: the role of the anesthetist in conducting
      the immuno-allergic investigation].
AB  - When peri-anaesthesia anaphylactic and/or anaphylactoid reactions occur,
      anaesthetist is the first investigator: the quality of immuno-allergological
      investigations depends on these initial investigational procedures. We have used
      sample kits for several years in order to make easier the immediate
      investigation. From retrospective analysis of the allergic complications which
      happened in 1997, the importance of these sample kits as well as the
      anaesthetist's part in the immuno-allergological management are examined. Nine
      observations were itemized (0.047%): 3 generalized erythema observations (grade
      I), in which atracurium was incriminated twice, and propacetamol once; 2
      observations of grade II, in which vecuronium (elevated tryptase) and atracurium
      were incriminated; 4 anaphylactic shocks, in which three neuromuscular blocking
      drugs (suxamethonium, vecuronium and pancuronium), and one antibiotic
      (cloxacilline) were incriminated. The use of sample kits allowed an early
      diagnosis approach, confirmed by skin tests. Diagnosis should be thought closely
      between anaesthetists and immunologists for investigations.

PMID- 9657023
TI  - [Propacetamol and new occupational contact dermatitis].
AB  - We describe the cases of three hospital nurses who presented eczematous lesions
      on the hands and eyelids. They worked in surgery department or in post
      anaesthesia recovery room, all preparing syringes of Pro-Dafalgan (propacetamol:
      parenteral paracetamol form). They were not sensitive to oral paracetamol or
      occupational products and latex. During week-end or holidays when they stopped
      handling Pro-Dafalgan, the eczema recovered but relapsed on working. A few cases
      are described in the literature so precautions begin to be preconized for
      healthcare workers but they are not usually in practice. Test performed with
      solvent, paracetamol, latex, formol and other hospital allergen tests were
      negative. The only allergen would be propacetamol because all tests performed
      with it were strongly positive. Following the official evaluation method in
      pharmacovigilance, based on chronologic and semiologic criterias, considering the
      positivity of rechallenge and specific tests, propacetamol imputability was
      probable in all our cases. It is preconized to declare cases to Regional
      Pharmacovigilance Centers to complete information about handling risks of this
      very usual analgesic.

PMID- 9657024
TI  - Nasal allergen challenge and immunotherapy control.
AB  - Nasal allergen challenges, despite not reproducing exactly natural allergen
      exposure, are a very useful method to understand the complex cellular kinetics
      and cellular interactions that occur in allergic rhinitis. Cell-specific soluble
      mediator measurements can give useful diagnosis information as well as
      complementary information regarding the monitoring of specific immunotherapy. In
      this article we present data concerning eosinophil cationic protein and tryptase
      measurements after nasal allergen and the influence of specific immunotherapy on
      nasal peak flow before and 1, 2 and 3 years after starting immunotherapy.

PMID- 9657025
TI  - [Systemic contact dermatitis].
AB  - The field of systemic contact dermatitis is particularly interesting for an
      allergist. To think of an allergen with cross-reaction and monosensilization
      should be the first reflex when an enquiry into a skin problem involves an
      allergic symptom. The three examples quoted involve Peruvian balm as the
      sensitizing agent. The causal triggering medicines are all vegetal extracts.

PMID- 9657026
TI  - [Cancer of the kidney in adults. Apropos of 60 cases].
AB  - The authors report a series of 60 cases of renal cancer observed over a 10-year
      period. Patients consisted of 35 women (58%) and 25 men (42%), with a mean age of
      52 years (range: 21-72 years). The clinical features were polymorphic, dominated
      by loin pain (76%), haematuria (75%), a lumbar mass (46%), alteration of the
      general state (30%). The diagnosis was established by ultrasonography in 58
      patients and CT scan in 38 patients. The mean tumour diameter was 11.5 cm (5-25
      cm) and two cases presented bilateral tumours. The tumour was located in the
      upper pole in 40% of cases and was mid-renal in 30% of cases. The time to
      diagnosis ranged from 2 months to 3 years. Staging reflected the advanced stage
      of the cancer. Treatment was surgical for 53 patients (88%). A lumbar incision
      was generally performed (83%). The surgical procedure consisted of nephrectomy
      and regional or hilar lymph node dissection. Nephrectomy was simple for 27% of
      patients, radical for 69% of patients and partial for 4% of patients. The
      postoperative course was marked by one death due to pulmonary embolism, and a
      stercoral fistula in 2 patients. Histological examination of the specimen showed
      clear cell adenocarcinoma in 92% of cases. The tumour weight was often
      considerable, with a maximum of 3.750 kg. The lymph nodes removed were invaded in
      50% of cases. The mean follow-up was 46 months (12 to 120 months). Follow-up was
      normal at 3 years for 23 patients (43%) and at 10 years for 4 patients (8%).
      Tumour recurrence in the renal compartment was observed in 3 patients after 3
      years. Asynchronous metastases occurred in 10 patients (23%). The mean interval
      to metastases was 20 months (4 to 36 months).

PMID- 9657027
TI  - [Renal angiomyolipoma. Apropos of 11 cases].
AB  - The authors report their experience of 11 cases of renal angiomyolipoma over an
      interval of 20 years, observed in 10 women (90.9%) and one man (9.1%) with a mean
      age of 46 years (range: 21 to 63). Clinical symptoms were dominated by loin pain
      (100%), haematuria (45.4%), lumbar mass (72.7%), fever (18%). In one woman, AML
      was associated with "tuberous sclerosis". Preoperatively, the diagnosis was
      established by ultrasound and CT scan in 45.4% of patients. The size of the
      tumour varied from 7 to 14 cm in 10 patients and in one patient was only about
      3.6 cm. Two women had bilateral tumours. Treatment consisted of total nephrectomy
      in 7 patients, partial nephrectomy in 3 patients and tumourectomy in one patient.
      The purpose of this study is to analyse the epidemiologic, diagnostic and
      therapeutic aspects of this disease.

PMID- 9657028
TI  - [Discovery of a renal chromophobe cell carcinoma in a pregnant woman. Apropos of
      a case].
AB  - We report the case of a young pregnant woman with a malignant tumour of the
      kidney suggestive of oncocytoma. Because of the pregnancy, preoperative staging
      consisted of abdominal ultrasound and magnetic resonance imaging. Caesarean
      section was performed. Several days later, surgical exploration of the kidney was
      performed with tumourectomy and frozen section analysis: radical nephrectomy was
      finally performed. The definitive histology was chromophobe renal cell carcinoma.
      This is a rare tumour of the kidney, with its own characteristics allowing
      histopathological diagnosis and with a better prognosis than renal cell
      carcinoma. In the literature, pregnancy, a situation of immune depression, does
      not increase the prevalence of malignant neoplasms.

PMID- 9657029
TI  - [A triple association: renal malacoplakia, bilateral vulvar hypertrophy, upper
      limb algodystrophy].
AB  - The authors report a case of malakoplakia of the left renal parenchyma, an
      uncommon site for an inflammatory disease first described in the bladder by
      Michaelis and Guttmann in 1902 and Von Hansmann in 1903. This case was observed
      in a 24-year-old girl with no urological history, presenting with bilateral
      vulval hypertrophy and reflex sympathetic dystrophy of the upper limbs, in whom
      malakoplakia of the left kidney was discovered incidentally. Intravenous
      urography showed two large kidneys with a stretched appearance of the renal
      pelvis. Pathological examination of the partial nephrectomy specimen revealed the
      diagnosis of malakoplakia, an inflammatory diseases of the renal parenchyma. The
      pathogenesis has been only partially elucidated, but probably involves a disorder
      of macrophage function.

PMID- 9657030
TI  - [Laparoscopic adrenalectomy. A general review of a current technic].
AB  - The anatomical situation of the adrenal gland explains the diversity of the
      surgical incisions used for adrenalectomy. Laparoscopic adrenalectomy was first
      performed in 1992. It allows eradication of small adrenal lesions, which are
      often incidental findings. There are two routes of laparoscopic access to the
      adrenal gland: transperitoneal and retroperitoneal. Laparoscopy allows excellent
      operative exposure, reduction of postoperative pain and hospital stay and rapid
      convalescence. Retroperitoneoscopy, by allowing direct access to the
      retroperitoneum, is more rapid than the transperitoneal route.

PMID- 9657031
TI  - [Percutaneous endopyelotomy. Apropos of 27 cases].
AB  - 27 percutaneous endopyelotomies were performed in 27 patients from February 1989
      to January 1996 to treat 20 cases of congenital hydronephrosis and 7 cases of
      acquired stenosis. Strictures of uretero-pelvic junction were treated by
      electrocautery with postoperative drainage using a double J stent in 11 cases, or
      Redon drain in 16 cases. The evaluable results for 25 patients with a mean follow
      up of 11 months showed an overall success rate of 80%. This technique is the
      treatment of choice for acquired stenosis and stage I and II congenital
      hydronephrosis (Cendron).

PMID- 9657032
TI  - Aetiopathogenesis and treatment of idiopathic retroperitoneal fibrosis.
AB  - Idiopathic retroperitoneal fibrosis (IRF) is a rare urological disease, for which
      many pathogenic theories have been proposed. The authors report a series of 13
      cases of IRF in order to evaluate the clinical, diagnostic, laboratory,
      therapeutic and prognostic aspects. They also report a rare case (the ninth case
      reported in the literature) of multifocal fibrosclerosis. A possible genetic
      predisposition was studied by testing for the presence of immunophenotype HLA
      B27; this test was positive in 44% of cases. A study of the immunological profile
      and lymphocyte populations revealed the typical features of chronic immune
      disease. Experience with medical and surgical treatment is reported, comparing
      various procedures: ureterolysis followed by application of a vascularized
      omental flap over the ureter (without subsequent corticosteroid therapy) gave the
      best results, with complete resolution of the symptoms and long-term successful
      alleviation of ureteric obstruction in 100% of patients, with a mean follow-up of
      58 months.

PMID- 9657033
TI  - [Vestigial retrorectal dermoid cyst. Apropos of a case].
AB  - A case of recto-rectal congenital development cyst is described in 35-year-old
      man. This cyst presented in the form of voiding symptoms. Computed tomography
      revealed the relation and components of the development cyst. Treatment consisted
      of complete surgical excision via a transabdominal approach.

PMID- 9657034
TI  - [Tumors of the bladder in women. Epidemiologic and therapeutic aspects. Apropos
      of 40 cases].
AB  - Bladder tumours in women. Epidemiological aspects and treatments, based on a
      series of 48 cases. Bladder tumours are more frequent in men than in women, in
      whom they present certain epidemiological, clinical and therapeutic
      characteristics. The authors report a retrospective study of 48 cases of bladder
      tumour in women, observed in the urology department over a 20-year period. These
      tumours represented 4.2% of all bladder tumours. The patients had a mean age of
      59 years (range: 29 to 77). Only one patient was a smoker (2%). Haematuria was
      present in 93% of cases, and signs of bladder irritation were present in 60% of
      cases. All tumours were transitional cell carcinomas. The tumour was classified
      as stage 0 in 10 cases (20.9%), stage A in 15 patients (31.2%), stage B in 22
      patients (45.8%) and stage C in 1 case (2.1%); no patients (0%) were classified
      as stage D. Our therapeutic protocol was established as a function of the stage
      of tumour invasion. For example, superficial tumours were treated conservatively
      by transurethral resection, either alone or combined with intravesical
      instillation. Radical surgery was performed whenever possible for invasive
      tumours. External urinary diversion was performed in 11 cases,
      ureterosigmoidostomy in 3 cases and enterocystoplasty in 5 cases. The clinical
      course of the 15 superficial tumours was marked by recurrence in 5 cases, while
      that of the 23 invasive tumours was marked by local recurrence (3 cases), renal
      failure (1 case) and 3 deaths.

PMID- 9657035
TI  - [Paratesticular malignant mesothelioma. Presentation of a case].
AB  - We report a case of malignant mesothelioma of tunica vaginalis in a 65-year-old
      man. The clinical course was marked by local relapse and distant metastases.
      Based on a review of the literature, the authors discuss the clinical,
      epidemiological and therapeutic aspects.

PMID- 9657036
TI  - Basic studies on N''-ursodeoxycholyldiethylenetriamine-N,N,N'-triacetic acid for
      the dissolution of calcified gallstones.
AB  - A novel calcium-chelating agent, N"-ursodeoxycholyldiethylenetriamine-N,N,N'
      triacetic acid (UDCA-DTTA), was synthesized to study its ability to dissolve
      calcified gallstones. The chelating activity of the compound was demonstrated by
      dissolving calcium carbonate in vitro at a high dissolution rate. In the presence
      of the agent, sliced human gallstone with a composition of more than 50% calcium
      bilirubinate was thoroughly dissolved, indicating that calcium bilirubinate was
      dissolved from the gallstone. The ability to dissolve calcium was comparable to
      that of EDTA. However, the laminar structure of the sliced gallstone did not
      disappear in the presence of EDTA, whereas the structure disappeared in the
      presence of UDCA-DTTA. All these results indicate that UDCA-DTTA is an
      interesting compound as a parent substance for developing a prodrug for an oral
      or intravenous agent to dissolve calcium-containing gallstones.

PMID- 9657037
TI  - Effect of replacing a high linoleate oil with a low linoleate, high alpha
      linolenate oil, as compared with supplementing EPA or DHA, on reducing lipid
      mediator production in rat polymorphonuclear leukocytes.
AB  - The fatty acid composition of rat polymorphonuclear leukocytes (PMN) was modified
      by diets supplemented with a high linoleate (LA) safflower oil (76% LA), mixtures
      of eicosapentaenoate (EPA) and safflower oil (EPA(20) containing 20% EPA and 61%
      LA, EPA(40) containing 40% EPA and 46% LA), mixtures of docosahexaenoate (DHA)
      and safflower oil (DHA(20) containing 20% DHA and 61% LA, DHA(40) containing 40%
      DHA and 46% LA) or a high alpha-linolenate (alpha-LNA) perilla oil (57% alpha-LNA
      and 13% LA), and then lipid mediator production in casein-induced peritoneal PMN
      were compared. EPA and DHA were relatively ineffective in reducing platelet
      activating factor (PAF) production; a statistically significant reduction was
      observed only in the DHA(40) group. In contrast, perilla oil reduced PAF
      production by 50% as compared with safflower oil. Arachidonate (AA) in the PAF
      precursor, 1-alkyl-2-acyl-glycerophosphocholine, was roughly correlated with PAF
      production, but EPA and DHA in the precursor lipid were relatively unrelated. On
      the other hand, both PGE2 and LTB4 production correlated positively with AA and
      negatively with EPA and DHA in PMN phospholipids; EPA tended to be somewhat more
      effective than DHA in reducing PGE2 and LTB4 formation; the activity of perilla
      oil was no less than EPA(20). Thus, replacing safflower oil with perilla oil was
      no less effective than supplementing safflower oil with EPA or DHA (at 40% of
      total fatty acids) in reducing lipid mediator production in rat PMN.

PMID- 9657038
TI  - Determining specific gravity, specific heat, and surface area of rabbits for a
      possible thermodynamic approach to body temperature change.
AB  - In order to investigate the mechanisms of body temperature change from a
      thermodynamic aspect, we investigated the specific gravity, specific heat and
      surface area of rabbit in situ. We obtained the following results. 1. The
      specific gravity of normal, shorn and ecdysed rabbits is 0.94, 0.95 and 0.97,
      respectively. 2. The specific heat of normal, shorn and ecdysed rabbits is 0.95,
      0.89 and 0.69 cal/g.K, [corrected] respectively. 3. The surface area of the
      rabbit was also measured by using the weight of aluminum foil which covered the
      surface.

PMID- 9657039
TI  - Mechanisms for 5-fluorouracil resistance in human colon cancer DLD-1 cells.
AB  - A 5-fluorouracil (5-FU)-resistant subline, DLD-1/5-FU, was established by
      repeated 5-d exposures of human colon cancer DLD-1 cells to 5-FU. DLD-1/5-FU
      cells were 41- and more than 75-fold resistant to 96-h and 1-h exposures to 5-FU,
      respectively. When exposed to 5-FU, DLD-1/5-FU cells exhibited marked resistance
      to in situ thymidylate synthase (TS) inhibition by 5-FU as compared to DLD-1
      cells, and incorporation of 5-FU into cellular RNA in DLD-1/5-FU cells decreased
      to 25% of that in DLD-1 cells. As causes of resistance to DNA and RNA-directed
      actions of 5-FU, remarkable reduction of intracellular levels of both 5
      fluorouridine 5'-triphosphate (FUTP) and 5-fluoro-2'-deoxyuridine 5'
      monophosphate (FdUMP) in DLD-1/5-FU cells was confirmed. It was found that
      activities of uridine kinase, orotate phosphoribosyltransferase and thymidine
      kinase of DLD-1/5-FU cells were significantly lower than those of the parent
      cells. Intracellular levels of TS were similar between the two cell lines. These
      results indicated that the mechanism of resistance to 5-FU in DLD-1/5-FU cells
      involves reduced enzymatic activation of 5-FU.

PMID- 9657040
TI  - Separation of phospholipase A2 in Habu snake venom by glycyrrhizin (GL)-affinity
      column chromatography and identification of a GL-sensitive enzyme.
AB  - By means of glycyrrhizin (GL)-affinity and Mono S column chromatographies (HPLC),
      at least four GL-binding proteins (p25, p17, p15-1 and p15-2) in the two Superdex
      fractions (P-II and P-III fractions) from Habu snake venom were selectively
      purified. By determination of their N-terminal partial amino acid sequences, a
      metalloprotease (p25) and three GL-binding phospholipases A2 (gbPLA2s) [PA2Y
      (p17), PA21 (p15-1) and PA2B (p15-2)] were identified. PA2B (lysine-49 PLA2) was
      found to be the most sensitive to GL because (i) it strongly bound to a GL
      affinity column; and (ii) its enzyme activity was selectively inhibited by low
      dose (ID50 = approx. 1.5 microM) of GL, but not by GA. Furthermore, these three
      gbPLA2s were phosphorylated by casein kinase II (CK-II) in vitro and GL inhibited
      the CK-II-mediated stimulation of their enzyme activities in vitro.

PMID- 9657041
TI  - Enhancement of the DNA damaging activity of N-nitrosodimethylamine by di-(2
      ethylhexyl)phthalate in somatic cells in vivo of Drosophila melanogaster.
AB  - The co-genotoxic effect of di-(2-ethylhexyl)phthalate (DEHP) was studied in an in
      vivo Drosophila genotoxicity test. DEHP is categorized as a non-genotoxic
      carcinogen. In this study, DEHP also did not show genotoxicity in Drosophila.
      When larvae were simultaneously treated with DEHP and N-nitrosodimethylamine
      (NDMA), the DNA damaging activity of NDMA was increased in the Drosophila DNA
      repair test. Furthermore, DNA double strand breaks were increased by the same
      treatment of Drosophila. These results suggest that DNA double strand breaks
      cause the co-genotoxic effect of DEHP in Drosophila.

PMID- 9657042
TI  - Formation of reactive oxygen intermediates might be involved in the trypanocidal
      activity of gallic acid.
AB  - We investigated the mechanism of the trypanocidal activity of gallic acid (GA).
      GA-induced trypanocidal activity was significantly reduced by pretreatment with
      superoxide dismutase (SOD) and/or catalase. The ESR technique with 5,5-dimethyl-1
      pyrroline N-oxide (DMPO) as a spin trapping agent revealed that a DMPO-OH adduct
      was detected in culture medium containing GA. The intensity of ESR signals of the
      DMPO-OH adduct was increased in a time dependent manner. SOD also inhibited the
      formation of GA-induced DMPO-OH adducts. Furthermore, GA enhanced DNA single
      strand breaks induced by Fenton reagent. These results suggest the possibility
      that GA acts as pro-oxidant for trypanocidal activity.

PMID- 9657043
TI  - Metabolism and pharmacokinetics of orally administered saikosaponin b1 in
      conventional, germ-free and Eubacterium sp. A-44-infected gnotobiote rats.
AB  - The metabolic fate of saikosaponin b1 (1) was investigated using conventional,
      germ-free and Eubacterium sp. A-44-infected gnotobiote rats. After the oral
      administration of 1 to germ-free rats at a dose of 50 mg/kg, no metabolite was
      detected in the plasma, the cecal contents or the cumulative feces through the
      experiment. On the other hand, when 1 was orally given to the Eubacterium sp. A
      44-infected gnotobiote rats, considerable amounts of its metabolites,
      prosaikogenin A (2) and saikogenin A (3), were detected in the rat plasma with
      the respective AUC0-10 h values of 17,424 and 22,260 pmol.min/ml, similar to the
      case of its oral administration to conventional rats (AUC0-10 h values of 9,936
      and 12,414 pmol.min/ml for 2 and 3, respectively). Furthermore, significant
      amounts of both metabolites were detected in the cecal contents and the
      cumulative feces of the gnotobiote and conventional rats, but not in those of the
      germ-free rats, within 10 h after the administration. Fecal and cecal activities
      of hydrolyzing 1 and 2 were found in the gnotobiote and conventional rats, though
      there were no detectable activities in the germ-free rats. Accordingly, both
      hydrolyzing activities in the intestinal bacteria, such as Eubacterium sp. A-44,
      are essential for the appearance of 2 and 3 in the rat plasma and cumulative
      feces, since orally administered 1 was poorly absorbed from the gastrointestinal
      tract.

PMID- 9657044
TI  - Antiosteoporotic activity of the stems of Sambucus sieboldiana.
AB  - We previously found that a methanolic extract of the stems of Sambucus
      sieboldiana inhibited bone resorption in organ culture. In this study, we further
      fractionated the methanol extract guided by the activity towards bone resorption
      stimulated by parathyroid hormone (PTH) in vitro. The ethyl acetate fraction
      (EtOAc Fr.) of the methanolic extract inhibited PTH-stimulated bone resorption of
      neonatal mouse bones, and the inhibitory activity was more potent than those of
      other fractions. Oral administration of the EtOAc Fr. (50 and 100 mg/kg/d) to
      ovariectomized (OVX) rat prevented the decrease in bone mineral density (BMD) of
      the lumbar (L2-4) vertebra, indicating that the EtOAc Fr. is effective in vivo.
      Furthermore, the EtOAc Fr. (50, 100 and 150 mg/kg/d) decreased the serum calcium
      level elevated in low calcium dietary rats. The phenolic constituents of the
      EtOAc fraction were examined for their inhibitory effect on bone resorption
      stimulated by PTH in neonatal mouse bone. Among them, vanillic acid, vanillin and
      coniferyl alcohol showed significant inhibitory effects on bone resorption. Of
      the compounds examined, vanillic acid was found to have a significant inhibitory
      effect on the decrease of BMD in OVX mice. Therefore, the EtOAc Fr. of S.
      sieboldiana showed a suppressive effect on bone resorption in vitro and in vivo.
      In addition, the inhibitory effects of the EtOAc Fr. on bone resorption may be at
      least partly due to the inhibitory action of vanillic acid.

PMID- 9657045
TI  - Enhanced in vitro percutaneous penetration of salicylate by ion pair formation
      with alkylamines.
AB  - The apparent octanol/water partition coefficient (APC) of salicylate (SA)
      increased as the concentration of alkylamine (amyl, hexyl, heptyl, octyl and
      nonylamine) in aqueous phase increased, presumably through intermolecular ion
      pair formation between the negatively charged SA moiety and the alkylamine
      cation. The true partition coefficient (TPC) and the formation constant (Kf) of
      the ion pair were calculated from the partition data. The skin permeability of SA
      increased as the APC of SA increased, when 20-fold molar excess of alkylamine was
      added to the donor compartment. Permeability of ion pairs (PAB) from the aqueous
      phase to a shed snake skin was estimated from the permeability data assuming 1:1
      ion pair. The methylene group contribution to the free energy of transfer of ion
      pairs from water to the shed snake skin was less than the reported value for
      nonionized drugs. This suggests that the ion pair is more polar by nature than
      nonionized molecules, even if ionic characteristics are masked to some extent by
      ion pair formation.

PMID- 9657046
TI  - Dose dependency in the gastrointestinal absorption of cefatrizine: correlation
      between in vivo and in situ.
AB  - We evaluated the dose-dependent (saturable) gastrointestinal absorption of
      cefatrizine, an aminocephalosporin transported by peptide carriers, in rats by a
      physiological mechanism-based approach to clarify its absorption characteristics
      and to examine the in vitro (in situ)-in vivo correlation in intestinal
      transport. With an increase in oral dose (mumol/5 ml/kg) from 5 (low) to 50
      (high), the intestinal absorption rate constant (ka), which was estimated by
      analysis of gastrointestinal disposition, decreased markedly, from 0.301 to 0.056
      min-1. This decrease was ascribable to the saturability of intestinal membrane
      transport, of which the concentration dependency in the perfused intestine was
      similar in extent to the dose dependency in ka. However, the apparent absorption
      rate constant (ka'), which was estimated by analysis of plasma concentrations
      after oral administration, decreased only modestly from 0.037 to 0.023 min-1.
      This was associated with the result that, at the low dose, ka' was far smaller
      than ka and comparable with k(g) (gastric emptying rate constant), suggesting
      gastric emptying-limited absorption. At the high dose, where intestinal
      cefatrizine absorption was less efficient, ka' was closer to ka than k(g). It was
      also observed that the bioavailability was close to unity, independent of dose,
      suggesting that the intestinal transit time is long enough to achieve complete
      absorption, even at the high dose, where intestinal cefatrizine absorption is
      less efficient. Thus, it was found that the effect of saturability in the
      intestinal transport of cefatrizine is apparently attenuated in its overall
      gastrointestinal absorption because of the involvement of gastric emptying and
      intestinal transit time as additional physiological factors to define absorption.
      It was also found that a scaling factor is required to correlate the intestinal
      membrane transport between in vitro (in situ) and in vivo, though this remains to
      be verified to be utilized for developing oral drug delivery strategies and
      optimizing oral drug therapy.

PMID- 9657047
TI  - Hepatic extraction of tacrolimus in rats with experimental liver diseases.
AB  - Tacrolimus, an immunosuppressive agent, is metabolized mainly in the liver and
      has shown large intra- and interindividual pharmacokinetic variability. We
      investigated the effect of liver dysfunctions on the pharmacokinetics of
      tacrolimus in rats with experimental liver diseases. Experimental hepatic failure
      was induced by CCl4-treatment or bile duct ligation. Tacrolimus (1 or 0.3 mg/kg)
      was administered intravenously or intraportally to the rats (n = 5-6 per group),
      and blood samples were collected over a 240-min period. The tacrolimus
      concentrations in the blood were then measured by a high-performance liquid
      chromatography-enzyme immunoassay. In the normal rats, the hepatic extraction
      ratio of tacrolimus (EH) was dose-independent, ranging from 0.556-0.598 at 0.3
      and 1.0 mg/kg doses. The EH were dose-dependent in the CCl4-treated rats and in
      the bile duct-ligated rats: the EH at 1.0 mg/kg dose were 0.158-0.170 and those
      at 0.3 mg/kg dose were 0.329-0.394. The intermediate EH of tacrolimus suggested
      that the clearance of tacrolimus depends not only on hepatic intrinsic clearance
      but also on hepatic blood flow. The present pharmacokinetic study also suggested
      that the decrease of EH and the dose-dependence of EH contribute to the elevation
      of blood tacrolimus concentrations and to the large variability in the
      pharmacokinetics of tacrolimus after oral administration in hepatic dysfunctions.

PMID- 9657048
TI  - Effectiveness and toxicity screening of various absorption enhancers using Caco-2
      cell monolayers.
AB  - We studied the enhancing and toxic effects of five different absorption enhancers
      on the transport of FITC-dextran with an average molecular weight of 4000 (FD-4)
      across Caco-2 cell monolayers, and their enhancing effects were also compared
      with those in rat intestine. The enhancing and cytotoxic properties of these
      enhancers were characterized using the following tests: measurement of the
      permeability coefficients of FD-4 and the transepithelial electrical resistance
      (TEER) in Caco-2, the release of cytosolic lactate dehydrogenase (LDH) and
      intracellular mitochondrial dehydrogenase (MDH) activity. All the absorption
      enhancers increased the permeability of FD-4 across Caco-2 cell monolayers and a
      good relationship was observed between the enhancement and their toxic effects.
      However, EDTA and Na-Cap were effective for improving the transport of FD-4
      across Caco-2 cells without serious cytotoxicity. At concentrations with low
      cytotoxicity, various absorption enhancers exihibited reversible effects on the
      TEER values in Caco-2 cell monolayers, except for 50 mM sodium salicylate (Na
      Sal). Moreover, we obtained a good correlation between the enhancement of these
      enhancers in Caco-2 cell monolayers and in rat large intestine. This finding
      indicated that the effectiveness of absorption enhancers in the Caco-2 monolayer
      system was similar to an in vivo rat system. Therefore, the screening system
      using Caco-2 cell monolayers is useful for examining the effectiveness and
      toxicity of absorption enhancers.

PMID- 9657049
TI  - Virus inactivation in superoxide dismutase preparations by ultraviolet light
      irradiation.
AB  - Viral inactivation in superoxide dismutase (SOD) derived from human red cells was
      carried out by ultraviolet light C (UVC) irradiation. With 400 J/m2 UVC
      irradiation, the titer of canine parvovirus (CPV, a nonenveloped virus), M13
      bacteriophage (M13, a nonenveloped phage) and vesicular stomatitis virus (VSV, an
      enveloped virus), which were spiked into SOD solution, were reduced by > 4.6
      log10 (detection limit), 7.0 log10 and 6.2 log10, respectively. The SOD activity
      was maintained and the band pattern of SOD on an electrophoresis gel was not
      changed even by 1000 J/m2 UVC irradiation. These results indicate that UVC
      irradiation is a promising method for the inactivation of both enveloped and
      nonenveloped viruses in SOD preparations while maintaining its activity.

PMID- 9657050
TI  - Formation of adenosine 3'-monophosphate in rat liver mitochondria.
AB  - An unknown adenine-related compound (UKC) in rat liver mitochondria was
      characterized. Based on the sensitivity to periodate oxidation, nuclease P1
      digestion, property of fluorescence derivatization, elution behavior on different
      separation modes of HPLC columns and the mass spectrum of purified UKC, the UKC
      was identified as adenosine 3'-monophosphate (3'-AMP), an intracellular P-site
      inhibitor of adenylate cyclase. 3'-AMP may be enzymatically produced from RNA in
      rat liver mitochondria in temperature- and time-dependent manners. A partial
      characterization of 3'-AMP forming enzyme is included.

PMID- 9657051
TI  - Metabolism of puerarin and daidzin by human intestinal bacteria and their
      relation to in vitro cytotoxicity.
AB  - When puerarin or daidzin were incubated for 24 h with human intestinal bacteria,
      two metabolites, daidzein and calycosin, were produced from them, respectively.
      The metabolic time course of puerarin was as follows: at an early time, puerarin
      was converted to daidzin, and then calycosin. The metabolic time course of
      daidzin by human intestinal bacteria was also similar to that of puerarin. The in
      vitro cytotoxicities of these metabolites, calycosin and daidzein, were superior
      to those of puerarin and daidzein.

PMID- 9657052
TI  - Effect of over-expressed hsp26 on cell growth of yeast.
AB  - Mammalian small heat shock protein (s-hsp) has been suggested to participate not
      only in stress tolerance but also in the growth regulation and differentiation of
      cells. To confirm the role of s-hsp in cell growth, we investigated the
      relationship between the expression of hsp26 and yeast cell growth. Cells lacking
      constitutive hsp70, ssa1ssa2, have been known to have a poor growth rate and to
      over-express hsp26 and some other hsps. We obtained several cell clones of
      ssa1ssa2 whose doubling times were different from one another. The amount of
      hsp26 was closely linked to the doubling time of ssa1ssa2 cells. This result
      suggests that the expression of hsp26 modulates the growth rate of yeast cells
      lacking constitutive hsp70, similarly to mammalian cells.

PMID- 9657053
TI  - A protease sensitive region of plant and animal ribonucleases belonging to the
      RNase T2 family.
AB  - Recombinant RNase LE from tomato and squid liver RNase Tp, typical plant/animal
      type RNases belonging to the RNase T2 family, were subjected to limited digestion
      with several proteases, and the cleavage sites were analyzed by Edman
      degradation. Recombinant RNase LE was cleaved specifically at the 24th Lys by
      lysylendopeptidase and trypsin, and RNase Tp was cleaved at the 21st Glu by V8
      protease. These cleavage sites are located very close to those where the cleavage
      during preparation of several animal RNase T2 family enzymes was observed. From
      this finding, it was concluded that the short segment around the 20th amino acid
      residue in plant/animal RNases is located on the surface of the molecules and
      forms loops, and is thus very sensitive to proteases.

PMID- 9657054
TI  - Thalidomide promotes the release of tumor necrosis factor-alpha (TNF-alpha) and
      lethality by lipopolysaccharide in mice.
AB  - We investigated the in vivo effects of thalidomide on the production of tumor
      necrosis factor-alpha (TNF-alpha). An in vivo systemic release of TNF-alpha
      occurred after the injection of lipopolysaccharide (LPS) in male ddY mice, and
      the TNF-alpha serum levels reached 652.2 +/- 75.7 pg/ml 90 min after the
      injection of LPS (0.3 mg/kg, i. p.). When thalidomide (1, 3, or 6 mg/kg) was
      administered intraperitoneally 3 h before the injection of LPS (0.3 mg/kg, i.
      p.), thalidomide markedly enhanced LPS-induced TNF-alpha release in a dose
      dependent manner. The TNF-alpha serum levels at 90 min were 640 +/- 58.6, 1985 +/
      132.6, and 2795 +/- 203.5 pg/ml, respectively, compared to 628.6 +/- 64.4 pg/ml
      in mice treated with LPS-alone. Pretreatment with a single injection of
      thalidomide (1, 3, or 6 mg/kg, i. p.) dose-dependently increased the subsequent
      mortality caused by a challenge with LPS (15 mg/kg, i. p.), a dose that caused
      death in 10% of the control mice. We conclude that thalidomide enhances in vivo
      TNF-alpha secretion and the lethality of LPS in mice.

PMID- 9657055
TI  - Anthraquinones from Neonauclea calycina and their inhibitory activity against DNA
      topoisomerase II.
AB  - In a series of searches for DNA topoisomerase II inhibitors from naturally
      occurring compounds, a wood extract of Neonauclea calycina MERR. (Rubiaceae)
      showed a moderate effect in vitro. Purification of the extract resulted in the
      isolation of seven known anthraquinones. The structures were characterized as
      damnacanthal, rubiadin 1-methyl ether, nordamnacanthal, morindone, damnacanthol,
      lucidin 3-O-primeveroside and morindone 6-O-primeveroside by spectral analysis,
      respectively. Damnacanthal and morindone showed an intensive inhibitory effect
      against topoisomerase II (IC50: 20 micrograms/ml and 21 micrograms/ml).

PMID- 9657056
TI  - Trypanocidal effects of curcumin in vitro.
AB  - During the course of study searching for the antiparasitic agents from natural
      compounds, we found that curcumin showed cytotoxicity against African
      trypanosomes in vitro. The LD50 values of curcumin were 4.77 +/- 0.91 microM for
      bloodstream forms and 46.52 +/- 4.94 microM for procyclic forms of Trypanosoma
      brucei brucei (GUTat 3.1 clone).

PMID- 9657057
TI  - Effect of guarana on exercise in normal and epinephrine-induced glycogenolytic
      mice.
AB  - The tonic action of water Guarana extract, (Paullinia cupana MART.), was
      investigated in normal, exercised, and epinephrine-induced glycogenolytic mice. A
      water extract of Guarana (GW) (500 mg/kg) increased the blood glucose level (p <
      0.001) and decreased the liver glycogen contents of mice 60 min after oral
      maltose administration (p < 0.05). GW also significantly suppressed exercise
      induced hypoglycemia (60 min: p < 0.05). However, GW did not affect the blood
      glucose in epinephrine-induced glycogenolytic and exercise mice. These findings
      indicate that the suppressive mechanism of hypoglycemia might be due to the
      promotion of glycogen resolution.

PMID- 9657058
TI  - The pragmatics of "madness": performance analysis of a Bangladeshi woman's
      "aberrant" lament.
AB  - A fine-grained analysis of the transcript of a Bangladeshi woman's lament is used
      to argue for an anthropology of "madness" that attends closely to performance and
      performativity. The emergent, interactive production of wept speech, together
      with the conflicting use to which it is put by the performer and her relatives,
      is linked problematically to performance genres and to ethnopsychiatric indexes
      of madness. Tuneful weeping is taken by relatives to be performative of madness,
      in a sense something like Austin's. Yet, exploration of the divergent linguistic
      ideologies which are brought to bear on the lament not only enables more nuanced
      ethnographic treatment but also has reflexive ramifications for medical and
      psychological anthropology. This leads to a critique of the referentialism in our
      own treatment of language. The role played by transparent reference is
      overshadowed by indexicality and by dialogical processes of proposing and
      resisting labels for speech genres attributed to the "mad."

PMID- 9657059
TI  - Complexity and human health: the case for a transdisciplinary paradigm.
AB  - Transdisciplinary thinking is an emerging philosophy underpinning health social
      science. We advance a definition of transdisciplinary thinking and link it with
      complexity theory. Complexity theory's concern with non-linear relationships,
      interactive causality and emergent properties of systems compels researchers to
      adopt a transdisciplinary perspective. We construct a generic framework for
      analyzing health processes from diverse disciplines and apply it to coronary
      heart disease in the Australian Coalfields. Insights from this analysis support
      our argument that transdisciplinary thinking maximizes understanding of the
      complexity of human health.

PMID- 9657060
TI  - Symptoms of depression in elderly Korean immigrants: narration and the healing
      process.
AB  - This paper explores ways in which depressive symptoms are expressed by elderly
      Korean immigrants in the USA. Depressed elderly Korean immigrants in the
      Washington DC area were interviewed in depth to explore their conceptualizations
      of depression in terms of explanatory models and semantic networks. The
      expressions of depressive symptoms were influenced by linguistic and psycho-socio
      cultural factors, therapeutic behaviors, and efficacy of treatment. The data were
      interpreted in terms of traditional Korean medical principles, cosmological,
      socio-cultural, and religious influences, and an individual's family structural
      changes and acculturation. Findings indicate the construction of somatization
      among Korean elders is more complex than is generally reported: in most cases, a
      dynamic, holistic blend of processes appears to operate simultaneously, instead
      of as somatization in isolation. Informants placed different degrees of emphasis
      on psychologization or somatization, or the two combined. The roles of
      personality, value orientation, intellect, emotion, economic status, degree of
      acculturation, degree of dependence on children, living situation (with or not
      with children), and self-will or self-confidence are important influences on the
      depression symptoms in the psychologization-somatization continuum. The more self
      directed the informants are, the more they psychologize; the more other-directed,
      the more they seem to somatize. Names and symptoms of depression (a Western
      concept) and popular illnesses (traditional Korean concepts) were used
      interchangeably by the informants. When informants were asked to explain the
      signs and symptoms of depression and sadness, some described symptoms similar to
      the criteria of major depression in DSM-III (American Psychiatric Association),
      while others gave different symptoms and ways of expressing them. Some informants
      believed that symptoms and signs of depression can be concealed from others if
      one chooses to do so. Many felt that manifestations of depression can be
      controlled by willpower, personality, and self-care.

PMID- 9657061
TI  - Cultural formulation of psychiatric diagnosis. Psychotic depression and
      alcoholism in an American Indian man.

PMID- 9657063
TI  - High-frequency FSH and LH pulses in obese menopausal women.
AB  - We studied the pulsatile luteinizing hormone (LH) and follicle-stimulating
      hormone (FSH) secretory patterns, at early or intermediate years of menopause in
      seven normal women with different degrees of obesity, taking blood samples every
      minute for 40 min to 2 h. The hormones were assayed with an immunoradiometric
      assay (IRMA) system, analyzing with the cluster pulse algorithm. All women showed
      hormone pulses every 8-10 min. In five of them were found periods of discrete
      pulses with oscillations of high amplitude alternating with periods of pulses of
      low amplitude. In two cases, the high-frequency oscillatory pattern with low
      amplitude was found around low mean levels of 22.8 and 25.7 IU/L. The LH
      oscillatory pattern also had a high frequency, but at a lower level, giving a
      high FSH/LH ratio. The coincidence index of FSH with LH peaks was 76.6%. We
      concluded that at menopause, the frequency of FSH and LH secretion increases with
      a high FSH/LH ratio. Obese menopausal women may have the same high-frequency
      oscillatory patterns, but at low levels.

PMID- 9657062
TI  - Growth hormone. A paracrine growth factor?
AB  - A number of tissues, including the brain, pituitary, immune system, placenta,
      mammary gland, and testis, may be self-contained units of GH regulation,
      production, and action. The production of GH and GH-releasing factors outside the
      hypothalamo-pituitary axis complements, rather than replaces, the traditional
      endocrine interactions between GH-releasing factors, GH, and its target tissues.

PMID- 9657064
TI  - Identification of endothelin receptor subtypes in sheep choroid plexus.
AB  - Endothelin (ET) and its G-protein-coupled receptors are distributed in a wide
      variety of tissues, including the brain. In this study, we have identified and
      characterized the endothelin receptor subtypes in sheep choroid plexus.
      Competitive binding experiments using [125I]ET-1 and the receptor subtype
      selective ligands, ET-1, ET-3, BQ-123, Sarafotoxin 6c, and [Ala1,3,11,15] ET-1
      demonstrated the presence of both ETA and ETB receptor subtypes in the ratio of
      30:70. In addition, a small fraction of the total binding sites exhibited
      affinities for ET-1 in the subpicomolar range. Chemical crosslinking of [125I]ET
      1 with bis(sulfosuccinimidyl)-suberate (BS3) to choroid plexus membranes revealed
      the presence of two bands, with apparent molecular masses of 89 and 45 kDa,
      corresponding to the ETA receptor, and three bands, with apparent molecular
      masses of 75, 58, and 33 kDa, corresponding to the ETB receptor. Of considerable
      interest was the finding that dimers of the [125I]ET-1-occupied ETA receptor
      could be identified by crosslinking, as could apparent dimers and tetramers of
      [125I]ET-1, but only when bound to receptor. In addition to mapping the
      distribution of ET receptors in sheep choroid plexus, our results strongly
      suggest that ET-1 binding to the ETA receptor leads to dimer formation.

PMID- 9657065
TI  - Differential effects of tumor necrosis factor-alpha and interleukin-1 on 3 beta
      hydroxysteroid dehydrogenase/delta 5-->delta 4 isomerase expression in mouse
      Leydig cells.
AB  - Immune-endocrine interactions are important to the regulation of Leydig cell
      steroidogenesis. We have shown previously that both tumor necrosis factor-alpha
      (TNF-alpha) and interleukin-1 beta (IL-1-beta) inhibit 8-bromo-cAMP-(8-Br-cAMP)
      stimulated steroidogenesis in mouse Leydig cells. TNF and IL-1 both inhibit cAMP
      stimulated testosterone production as well as mRNA and protein levels of
      cholesterol side chain cleavage enzyme (P450scc) and 17 alpha-hydroxylase/C17,20
      lyase (P450c17) in mouse Leydig cells. Neither TNF nor IL-1 affects basal levels
      of P450scc mRNA and protein. In the present study, we tested the effects of TNF
      and IL-1 on basal testosterone production and 8-Br-cAMP-stimulated 3 beta
      hydroxysteroid dehydrogenase/delta 5-->delta 4 isomerase (3 beta HSD) expression
      in Leydig cells. Purified and macrophage-depleted Leydig cells were cultured for
      5 d with daily changes of media, and then treated with increasing concentrations
      of recombinant mouse TNF or IL-1 in the presence or absence of 8-Br-cAMP (50
      microM) for 24 h. The media were collected for testosterone RIA and RNA and
      protein were extracted from cells. Basal testosterone production was inhibited by
      TNF, but not IL-1. Treatment of Leydig cells with 8-Br-cAMP alone caused a marked
      increase in 3 beta HSD mRNA, and protein levels. Both TNF and IL-1 inhibited cAMP
      stimulated 3 beta HSD mRNA and protein levels, but only TNF inhibited basal 3
      beta HSD expression. These results demonstrate that TNF and IL-1 have different
      effects on basal steroidogenesis in Leydig cells and suggest that TNF-mediated
      inhibition of basal testosterone production may be owing to the inhibition of
      basal 3 beta-HSD expression in Leydig cells.

PMID- 9657066
TI  - Regulation of the glucocorticoid receptor gene by the AP-1 transcription factor.
AB  - The glucocorticoid receptor (GR) is a ligand-activated nuclear transcription
      factor, and AP- 1 (Fos/Jun or Jun/Jun) is a transcription factor whose components
      are nuclear proteins encoded by c-fos and c-jun protooncogenes. Serum stimulation
      of serum-starved NIH 3T3 cells resulted in an approx 188-fold induction of c-fos
      mRNA at 30 min and an approximately ninefold induction of c-jun mRNA at 1 h,
      followed by an increase in GR mRNA levels at 3-12 hour (twofold). Sequential
      induction of cFos, cJun, and GR protein levels also occurred. Overexpression of
      the cFos protein in NIH 3T3 cells (NIH 3T3 [cFos 3] and NIH 3T3 [cFos 10]) caused
      an increase in the endogenous GR protein. Previous and present studies showed
      that a putative AP-1 site within the GR promoter binds AP-1 proteins (both Jun
      and Fos family members). To address the molecular mechanism involved in
      transcriptional activation of the GR gene, we investigated the relevance of AP-1
      binding complexes in this activation and in overall regulation of GR gene
      transcription. Transient transfection with a full length GR promoter linked to a
      luciferase gene into both NIH 3T3 (cFos 3) and NIH 3T3 (cFos 10) cells gave rise
      to an induction of luciferase activity. This induction was abolished following
      mutation or deletion of the GR AP-1 site from the promoter. These findings
      suggest that cFos is responsible for the induction of GR expression in serum
      stimulated NIH 3T3 cells, and serum growth factors may stimulate GR transcription
      by a cFos-dependent mechanism at the putative AP-1 site. These studies support a
      role for the AP-1 transcription factor in regulating GR gene expression.

PMID- 9657067
TI  - Stimulation of insulin and somatostatin release by two meglitinide analogs.
AB  - Several meglitinide analogs are currently under investigation as potential
      insulinotropic tools for the treatment of noninsulin-dependent diabetes. The
      present study aimed to further insight into the effect of these agents on the
      secretion of insulin, glucagon, and somatostatin by the isolated perfused
      pancreas. Both repaglinide (0.01 microM) and A-4166 (1.0 microM) stimulated
      insulin and somatostatin release, but failed to affect glucagon output, from
      pancreases exposed to 5.6 mM D-glucose. The secretory response of the B- and D
      cells to the hypoglycemic agents was much less marked than that caused by a rise
      in hexose concentration from 5.6-16.7 mM. Although repaglinide was tested at a
      concentration a hundred times lower than that of A-4166, the drug-induced
      increase in both insulin and somatostatin secretion persisted for a longer time
      after exposure to repaglinide, than to A-4166. The relevance of these findings to
      the use of meglitinide analogs as antidiabetic agents is double. First, they
      document that these drugs, although enhancing both insulin and somatostatin
      release, do not provoke an undesirable stimulation of glucagon secretion. Second,
      they indicate that even at a very low concentration, repaglinide provokes a
      protracted insulinotropic action, thus suggesting that the reversibility of the
      secretory response to this or other meglitinide analogs represents an intrinsic
      molecular attribute, unrelated to either their biological potency or the relative
      extent of B-cell stimulation.

PMID- 9657068
TI  - Depriving neonatal rats of milk from early lactation has long-term consequences
      on mammotrope development.
AB  - The sudden appearance of prolactin-releasing cells during the early postnatal
      period of the rat is initiated by a small milk-borne peptide. Depriving newborn
      rats of this early milk factor severely retards mammotrope differentiation during
      the neonatal period. In the present work, we extend our study of early milk
      deprivation to the adult. To this end, newborn litters were crossfostered onto
      mothers that had given birth the same day or one week earlier in order to deprive
      pups in the latter group of early milk. At 5, 15, and 30 d of age, rats deprived
      of such milk had decreased percentages of mammotropes (as measured by reverse
      hemolytic plaque assay, RHPA) when compared to nondeprived animals (P < 0.05). By
      45 d, the percentage of mammotropes was similar for the two crossfostered groups
      (P > 0.1) and this persisted through d 60. Subsequently, we assessed the
      secretory capacity of mammotropes from 60-d old rats to secretagogues and found
      that early milk deprivation had no effect on basal prolactin release (P > 0.1),
      but that it augmented hormone secretion evoked by thyrotropin-releasing hormone
      (TRH, 100 nM; P < 0.01). The inhibitory response to dopamine (DA; 1 microM) and
      the stimulatory response to angiotensin II (AGII; 100 nM) were not altered by
      early milk deprivation (P > 0.1). Taken together, these results demonstrate that
      factors in milk from early lactation are required for normal mammotrope
      differentiation, and that the delay induced by early milk deprivation leads to
      altered secretory function of mammotropes in adult animals.

PMID- 9657069
TI  - Leukemia inhibitory factor (LIF) modulates pro-opiomelanocortin (POMC) gene
      regulation in stably transfected AtT-20 cells overexpressing LIF.
AB  - Leukemia inhibitory factor (LIF) levels are elevated in sepsis and correlate with
      shock and poor prognosis. We have previously shown that lipopolysaccharide (LPS)
      administration induces hypothalamic and pituitary LIF expression in vivo, which
      is associated with the acute rise in circulating adrenocorticotrophic hormone
      (ACTH) levels. As AtT-20 cells respond to LIF, we established murine LIF (mLIF)
      stably transfected AtT-20 cell lines to study LIF regulation of pro
      opiomelanocortin (POMC) expression and ACTH secretion. Our results show that mLIF
      transfectants accumulated mLIF (up to 15.6 +/- 3.2 ng/mL after 24 h) as well as
      increased ACTH secretion (up to 2.4-fold above control cells) in conditioned
      medium. The magnitude of ACTH induction correlated with mLIF concentrations in
      different transfectants (r = 0.75-0.88, p < 0.05). Moreover, mLIF transfectants
      showed a higher sensitivity to CRH stimulation with an increased ACTH production
      within 8 h (p < 0.05), whereas control cells were responsive to CRH at 24 h.
      Additionally, mLIF transfectants exhibited a maximum threefold ACTH induction,
      compared to 1.7-fold in control cells. Furthermore, mLIF transfectants have a
      blunted dexamethasone-mediated inhibition of ACTH (35% inhibition in control
      cells vs no inhibition in mLIF-transfected cells at 24 h). These findings support
      and extend the previous observations of LIF acting at the pituitary level, and
      indicate that mLIF stably-transfected AtT-20 cells are a useful model for
      studying mLIF-mediated gene regulation in pituicytes.

PMID- 9657070
TI  - Regulation of the 11 beta-hydroxysteroid dehydrogenase in the rat adrenal.
      Decrease enzymatic activity induced by ACTH.
AB  - Patients with ectopic ACTH syndrome often develop hypertension and hypokalemic
      alkalosis with an abnormal increase in the ratio of plasma cortisol to cortisone,
      indicating that 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) activity is
      inhibited. Inhibition of 11 beta HSD allows access of cortisol or corticosterone
      to the mineralocorticoid receptor where it act as a mineralocorticoid. Two
      isozymes, 11 beta HSD-1 and 11 beta HSD-2, have been cloned and characterized.
      The rat adrenal expresses the mRNAs for 11 beta HSD-2 and, in lesser amounts, 11
      beta HSD-1. We investigated the effect of ACTH on the 11 11 beta HSD-2 activity
      in the rat adrenal. Rat adrenal cells zone fasciculata (ZF) were dispersed and
      incubated separately with increasing concentrations of ACTH for 90 min, and
      secretion of corticosterone (B) and 11-dehydrocorticosterone (A) in the media was
      measured by enzyme-linked immunoabsorbent assays (ELISA). The conversion of [3H]B
      to [3H]A in the presence of 0.5 mM NAD+ was evaluated in microsomes prepared from
      dispersed cells preincubated for 30 min with cyanoketone and metyrapone followed
      by incubation for 30 min with the same inhibitors, with and without 10 nM ACTH.
      The dispersed cells of the ZF produced significant amounts of A which increased
      with ACTH. The basal B/A ratio was 0.97 +/- 0.05. ACTH caused a concentration
      dependent increase in the ratio of B/A with a maximum ratio of 9.58 +/- 0.20.
      ACTH also inhibited the conversion of [3H]B to [3H]A in microsomes in which
      endogenous B production was inhibited by cyanoketone and metyrapone. ACTH did not
      change the K(m) for B conversion, but the Vmax was reduced significantly (1.73 +/
      0.43 pmol/min. mg protein), indicating that ACTH suppressed the 11 beta HSD-2 in
      a noncompetitive fashion. Dibutyryl cyclic AMP (dcAMP) also produced a
      concentration-dependent increase in the B/A ratio, but various concentrations of
      calcium did not affect the enzyme activity. In summary, adrenal cells treated
      with ACTH results in a significant increase in the ratio of B/A in the ZF owing a
      noncompetitive inhibition of the 11 beta HSD-2 via the ACTH receptor.

PMID- 9657071
TI  - Neonatal exposure to coumestrol, a phytoestrogen, does not alter spermatogenic
      potential in rats.
AB  - The objective of this study was to determine the effects of neonatal exposure to
      phytoestrogens on male reproductive function as adults. Male rats were injected
      either with 100 micrograms coumestrol or DMSO (controls) daily during their first
      5 d of life. Pituitary gland, testes, sex accessory organs, and blood were
      collected on d 60 of life. Serum testosterone, LH, and FSH levels were determined
      by RIA. Levels of steady-state mRNA for gonadotrophin subunits (LH beta and FSH
      beta were determined by Northern blot analysis and quantified by a scanning
      densitometer. Coumestrol had no effect on weights of testes and sex accessory
      organs, or sperm count. Similarly, there were no significant differences among
      serum concentrations of testosterone, LH beta and FSH of coumestrol-treated rats
      and those of controls. Whereas steady state levels of LH beta mRNA in coumestrol
      treated rats did not differ from those of controls, steady state levels of FSH
      beta mRNA increased (37%) in treated animals. However, the augmented FSH beta
      mRNA expression in coumestrol-treated rats did not negatively affect reproductive
      potential in male rats. We conclude that neonatal exposure to coumestrol does not
      alter reproductive organ structure or spermatogenic potential in male rats.

PMID- 9657072
TI  - Relationships between dopamine-induced changes in cytosolic free calcium
      concentration ([Ca2+]i) and rate of prolactin secretion. Elevated [Ca2+]i does
      not indicate prolactin release.
AB  - This study was undertaken to investigate the relationship between dopamine (DA)
      induced changes in the cytosolic calcium concentration ([Ca2+]i) and the rate of
      prolactin secretion using GH4ZR7, a rat pituitary cell line, which express only
      one subtype of D2 receptor. GH4ZR7 cells were loaded with Fluo-3, a fluorescent
      Ca2+ indicator, and then perifused with two different doses of DA (10(-7) mol/L
      and 5 x 10(-4) mol/L). We monitored changes in [Ca2+]i and rate of prolactin
      release simultaneously by attaching a spectrofluorometer to a dynamic perifusion
      system. DA has stimulatory and inhibitory effect on prolactin secretion in GH4ZR7
      cells; 10(-7) mol/LDA slightly increased [Ca2+]i and stimulated prolactin
      release, whereas 5 x 10(-4) mol/LDA decreased [Ca2+]i and inhibited prolactin
      secretion. When the cells were pretreated with pertussis toxin (PTX), 10(-7)
      mol/L DA had no significant change in [Ca2+]i while stimulating prolactin
      release, and 5 x 10(-4) mol/L DA reduced [Ca2+]i without having any significant
      effect on the rate of prolactin secretion. The results of this study demonstrate
      that changes in [Ca2+]i do not always correlate with the rate of prolactin
      release from lactotrophs. The dissociation between [Ca2+]i and prolactin release
      is somewhat expected considering the diverse role of [Ca2+]i and post-[Ca2+]i
      events, which can change the rate of prolactin release.

PMID- 9657073
TI  - The effect of GH therapy on the immunoreactive forms and distribution of IGFBP-3,
      IGF-I, the acid-labile subunit, and growth rate in GH-deficient children.
AB  - We have previously shown that the major correlates of growth following growth
      hormone (GH) therapy in growth hormone-deficient (GHD) children are changes in
      circulating insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP
      3), suggesting a synergistic interaction between IGF-I and IGFBP-3 (1). The first
      aim of this project was to examine the molecular forms of IGFBP-3 and the acid
      labile subunit (ALS), and to assess the changes in these molecular forms during
      GH administration to GHD children. Plasma samples from prepubertal GHD patients,
      prior to therapy and during the first year of GH treatment, were subjected to
      Western ligand and immunoblot analysis. Densitometric analysis of Western ligand
      blotting (WLB) showed a 76% increase in IGFBP-3 (p = 0.02), but a 56% decrease in
      36-kDa IGFBP-2 (p = 0.03) during GH therapy. Western immunoblot (WIB) analysis of
      IGFBP-3 revealed the presence of intact (40- to 45-kDa doublet) as well as a
      proteolyzed (28-kDa) form of IGFBP-3 in the serum of GHD and healthy children.
      Both immunoreactive forms of IGFBP-3 increased by 64% during GH therapy (intact p
      = 0.003; proteolyzed p = 0.0001). WIB analysis of the ALS showed an 84-to 86-kDa
      doublet, which increased by 41% with GH therapy (p = 0.01). The response to GH
      therapy, as measured by the height velocity standard deviation score (SDS)
      adjusted for bone age, correlated with the percent change in total IGFBP-3 (r =
      0.772, p = 0.002 by WIB), intact IGFBP-3 (r = 0.845, p = 0.0005 by WLB; r =
      0.541, p = 0.05 by WIB), and proteolyzed IGFBP-3 (r = 0.703, p = 0.007), as well
      as with the percent change in ALS (r = 0.813, p = 0.014). The second aim of this
      project was to assess the changes in distribution of the immunoreactive forms of
      IGFBP-3 and IGF-I among the ternary (ALS/IGFBP-3/IGF) complex, the binary (IGFBP
      3/IGF) complex, and uncomplexed IGF during the first year of GH therapy, and to
      explore further the correlation with growth response to GH. Plasma samples, prior
      to therapy and after the first year of GH treatment, were separated by neutral
      size-exclusion chromatography and then subjected to IGFBP-3 immunoradiometric
      assay (IRMA), IGFBP-3 WIB, and IGF-I IRMA analysis. IGFBP-3 increased in both the
      ternary (p < 0.0001) and binary (p = 0.01) complexes, but there was a shift in
      the percentage of IGFBP-3 from the binary to the ternary complex during GH
      therapy. Both intact and proteolyzed forms of IGFBP-3 were found in both the
      ternary and binary complexes, but the shift occurred primarily for the
      proteolyzed (28-kDa) form (p = 0.001). There was a significant increase in IGF-I
      in the ternary (p = 0.001) and binary (p = 0.005) complexes, but not in
      uncomplexed IGF-I. The percentage of IGF-I in the ternary complex increased (p =
      0.006), whereas the percentage of uncomplexed IGF-I decreased (p = 0.02), during
      GH therapy. Growth rate, assessed by the height velocity SDS for bone age,
      correlated best with the changes in ternary complex IGFBP-3 (r = 0.72, p = 0.01)
      and ternary complex IGF-I (r = 0.56, p = 0.10). In conclusion, GH treatment of
      GHD children results in significant increases of intact, proteolyzed, and total
      IGFBP-3, as well as an increase in ALS, which all correlate with the growth
      response to GH therapy. In addition, GH treatment results in increases in ternary
      complex IGFBP-3 and IGF-I, which also correlate with the response to therapy. We
      suggest that the formation of the ternary complex may be a determining factor in
      the somatic growth response.

PMID- 9657074
TI  - Thapsigargin shifts the Ca set point of parathyroid cells to lower extracellular
      [Ca].
AB  - The hypothesis that cytosolic calcium concentration ([Ca2+cyt]) is the primary
      regulator of parathyroid hormone (PTH) secretion is supported by a number of
      studies that show an inverse relationship between them. One agent shown to
      inhibit PTH secretion is thapsigargin, a sesquiterpene lactone that raises
      [Ca2+cyt] by inhibiting the Ca-ATPase that pumps Ca2+ from the cytosol into the
      lumen of the endoplasmic reticulum. Thapsigargin may act on the parathyroid cell
      other than to inhibit the Ca-ATPase, however, in ways that might also affect PTH
      secretion. We have tested its effects on functional parameters, such as protein
      synthesis, the exocytic machinery, and the ability of parathyroid cells to
      respond to different concentrations of extracellular Ca2+ ([Ca2+ex]). In
      particular, we have determined whether the inhibition of PTH secretion by
      thapsigargin is independent of or is modulated by changes in [Ca2+ex]. The
      results revealed no effects of thapsigargin on protein synthesis or the exocytic
      mechanisms within 2 h of treatment, and showed that [Ca2+ex] can modulate PTH
      secretion in the presence of thapsigargin. Its inhibition of PTH secretion,
      therefore, appears to rest on its ability to shift [Ca2+cyt] to higher levels,
      but the possibility that it interacts with the Ca receptor has not been
      eliminated. The results support the hypothesis that the primary regulator of
      steady-state PTH secretion is [Ca2+cyt].

PMID- 9657075
TI  - Quantitative measurement of islet glucagon response to hypoglycemia by confocal
      fluorescence imaging in diabetic rats: effects of phlorizin treatment.
AB  - We have shown that the glucagon irresponsiveness to hypoglycemia in diabetic rats
      is markedly improved by correction of hyperglycemia independent of insulin. In
      contrast, normalization of glycemia by insulin did not improve this response. To
      find out whether these glucagon responses reflect changes in islet glucagon, we
      directly quantified glucagon area and content in each pancreatic islet by using
      fluorescent immunostaining and computerized image analysis with confocal laser
      scanning microscopy (CLSM). The pancreases were analyzed in four groups of rats.
      1. Normal controls (NC, n = 4), streptozotocin (65 mg/kg) diabetic rats. 2.
      Diabetic untreated (DU, n = 4). 3. Diabetic Phlorizin-treated, (0.4 g/kg), twice
      daily for 4 d (DP, n = 4). 4. Diabetic insulin-treated, using sustained release
      (2-3 U/d) insulin implant for 5 d (DI, n = 4). Basal plasma glucose was 7.4 +/-
      0.3 mM in NC, increased to 14.5 +/- 2.2 mM in DU, which was normalized in DP (5.5
      +/- 0.5) and DI (6.7 +/- 0.8). Acute hypoglycemia (H) was induced by i.v. insulin
      injection. The rats were sacrificed 2 h after insulin injection and the pancreas
      was removed. By imaging with CLSM, we quantified: 1. Percent of glucagon
      containing A-cell area/islet area, 2. Fluorescence intensity per islet area,
      which indicated glucagon content in the islet. 3. Fluorescence intensity per
      glucagon area indicating glucagon concentration in A-cells. In NC, glucagon
      containing A cell area was 21 +/- 2% of the islet area, and glucagon intensity
      and concentration was 11 +/- 1 U and 36 +/- 3.0 U, respectively, in basal (O)
      state and did not change in (H). In DU, glucagon area increased 183% (O) and 166%
      (H), and islet glucagon intensity increased by 235% (O) (p < 0.05), but decreased
      to 135% in H. Glucagon area in DP and DI did not differ significantly from DU.
      However, hypoglycemia in DP increased glucagon intensity in islet further to 306%
      of normal control (p < 0.05), suggesting marked increase in glucagon content
      indicating increased synthesis. In contrast, DI compared to DP showed a decrease
      in glucagon intensity in islet (46 +/- 3, DP to 22 +/- 2 DI; p < 0.05) in (H)
      state. Glucagon concentration followed the same pattern as its intensity.
      CONCLUSION: 1. Increase in islet glucagon content in diabetic rats was associated
      with increase in glucagon containing A-cell area per islet. 2. Phlorizin-induced
      insulin independent correction of hyperglycemia increased glucagon content per
      islet in hypoglycemic state. This, in part, probably contributed to improved
      glucagon response to hypoglycemia observed earlier 3. Normalization of glycemia
      with insulin reduced glucagon content of each islet during hypoglycemia. This may
      explain, in part, unresponsiveness of glucagon to hypoglycemia often observed in
      insulin-dependent diabetes mellitus (IDDM) with intensive insulin therapy.

PMID- 9657076
TI  - Hormonal modulation of apoptosis in the rat adrenal gland in vitro is dependent
      on structural integrity.
AB  - The intact rat adrenal gland in short-term (3-h) organ culture may be amenable
      for the identification of factors involved in regulating adrenal cell apoptosis
      under defined conditions. In this model, culturing in the absence of trophic
      support (basal; control) triggered apoptosis in the intact rat adrenal gland;
      oligonucleosome formation, a measure of apoptosis, was 56.4-fold greater than
      that of glands snap-frozen at the start of incubation. Angiotensin II (Ang II)
      (100 nM) enhanced apoptosis by 67% over control. By contrast, adrenocorticotropin
      (ACTH) (100 nM) attenuated basal apoptosis by 59% and antagonized the enhanced
      apoptosis induced by Ang II back to the control level. Quartering of the glands
      enhanced basal oligonucleosome formation 182.2% greater than that of intact
      glands. Interestingly, quartering of the glands abolished the influences of Ang
      II and ACTH on apoptotic DNA fragmentation, but did not alter ACTH-induced
      corticosterone secretion. These data suggest that some level of gross adrenal
      structural information or compartmentalization, sufficiently disrupted by
      quartering, is required for the hormonal modulation of adrenal cell survival.

PMID- 9657077
TI  - Role of advanced glycation end products in aging collagen. A scanning force
      microscope study.
AB  - The collagen structure of young and old rats was examined using a scanning force
      microscope (SFM). Rat tail tendons of 8- and 24-month-old Wistar rats were frayed
      by two blades and examined using a Nanoscope III SFM. In the same tendons, the
      pentosidine concentrations, a marker of the Maillard reaction, were determined by
      HPLC. The SFM inspection of native fibrils produces images of collagen bundles,
      with parallel fibrils. The diameters of old rat collagen fibrils were large in
      comparison to the young ones. Moreover, fibrils obtained from old rats exhibited
      the same band interval, while the depth of the gap between two overlap zones
      showed a higher mean value with respect to young collagen. The pentosidine
      concentration was also higher in the old than in the young tendons. In
      conclusion, in the presence of an increased concentration of advanced glycation
      end products, significant structural alterations have been observed in old
      fibrils.

PMID- 9657078
TI  - Influence of age on oxidative bursts (chemiluminescence) of polymorphonuclear
      neutrophil leukocytes.
AB  - The release of reactive oxygen species (ROS) during neutrophil oxidative bursts
      is the last of a sequence of different steps leading to the neutralization of
      pathogen microorganisms. Using luminol-amplified chemiluminescence (LACL), the
      oxidative burst activity of neutrophils in elderly people (> or = 75 years) was
      compared with that in younger controls (39 years on average) after activation
      with both particulate (Candida albicans) and soluble (formyl-methionyl-leucyl
      phenylalanine; fMLP) stimulants. After Candida stimulation, a reduction in LACL
      was observed in the elderly subjects in comparison with the controls, but the
      difference did not reach statistical significance. After fMLP stimulation, the
      reduction in LACL was significant, thus suggesting that the Candida pathway of
      chemiluminescence production seems to be less affected than the fMLP pathway.
      This finding raises questions concerning the complex differences in the pathways
      of cell killing and ROS generation, and their efficacy in the elderly. Various
      possible explanations are discussed, all of which need further investigation.

PMID- 9657079
TI  - Age-related changes in gastric mucosal repair and proliferative activities in
      rats exposed acutely to aspirin.
AB  - The present study was designed to determine whether there are any age-related
      changes in the repair of acute gastric mucosal injury induced by aspirin in
      Fischer 344 rats. We have also examined the influence of aging on gastric mucosal
      proliferative activities, a major component of gastric mucosal defense and repair
      mechanisms. Our data demonstrated that aging was associated with significant
      delays in both resolution of gross mucosal injury and regeneration of the injured
      gastric mucosa. However, there were no correlations between the regeneration of
      the injured gastric mucosa and gastric mucosal expression of proliferating cell
      nuclear antigen and transforming growth factor-alpha immunoreactivities.

PMID- 9657080
TI  - Total knee arthroplasty in the elderly: patients' self-appraisal 6 and 12 months
      postoperatively.
AB  - The objective of this work was to study patients' self-appraisal of total knee
      arthroplasty (TKA) 6 and 12 months postoperatively, and to establish which
      factors determine dissatisfaction from surgery. The study group consisted of 79
      patients subjected to TKA who underwent rehabilitation in a specialized
      institution from which they were discharged home after becoming independently
      ambulatory and capable of independent home care. Data were collected by
      interviews and physical examinations which were conducted upon admission to the
      rehabilitation program and at the patients' homes 6 and 12 months
      postoperatively. Descriptive statistics and logistic regression were applied for
      data analysis. Results of the 1-year follow-up indicated a decrease in the
      prevalence of pain in the postoperated knee and improvement in ambulatory
      capacities. The frequency of reliance on a walking aid and the prevalence of pain
      in the nonoperated knee were not substantially changed, however. In 27% of the
      subjects pain in the nonoperated knee had worsened at 1 year. One third of the
      respondents expressed dissatisfaction from the operation. Outcomes of the
      logistic regression analysis pointed to pain in both the ipsi- and contralateral
      knee and to the limitations in using stairs as the variables which significantly
      affected the levels of dissatisfaction 1 year postoperatively. Dissatisfaction
      could have resulted from inappropriate expectations from either
      misinterpretations or limited prior knowledge of the likely results of the
      operation.

PMID- 9657081
TI  - Peripheral serotonin levels in women: role of aging and ethnicity.
AB  - Serotonin has been implicated to play an important role in regulating emotions
      and behavior, and it is well accepted that the platelet serotonergic system
      mirrors the presynaptic central serotonergic system. Since prevalence of
      psychiatric problems increases with age and women are known to be more vulnerable
      than men, the present investigation was carried out to study the relationship
      between serotonin activity and age in women. Levels of serotonin (5
      hydroxytryptamine, 5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA)
      were measured in platelets and plasma in women (n = 49) aged 40-84 years (30
      women aged 40-60 years and 19 women aged 61-84 years). There was a significant
      age difference between the two groups (mean: 47.6 +/- 5.91 years in the younger
      and 73.0 +/- 6.83 years in the older women, respectively, p < 0.00001). Platelet
      5-HT as well as 5-HIAA levels were significantly higher in older women as
      compared to those in the younger women (89.41 +/- 21.95 ng/10(8) platelets in
      younger vs. 112.9 +/- 36.07 in older women, p < 0.02, and 1.20 +/- 1.10 in
      younger vs. 2.19 +/- 1.88 ng/10(8) platelets in older women, p < 0.05,
      respectively). Pearson correlation coefficients determined in the combined group
      (n = 49) showed a significant positive correlation between platelet 5-HT and age
      (r = 0.31, p < 0.03). Plasma 5-HT levels on the other hand were lower in older
      women compared to those in the younger women (4.50 +/- 3.20 in younger vs. 1.04
      +/- 1.28 ng/ml plasma in older women, p < 0.0001) and a significant negative
      correlation was observed between plasma 5-HT and age (r = -0.44, p < 0.002).
      Plasma 5-HIAA concentration did not differ between the two groups. Platelet 5-HT
      levels in the younger group were independent of ethnicity. Since high serotonin
      activity has also been associated with psychiatric problems, our results of
      increased concentration of platelet 5-HT as well as 5-HIAA with age may have
      implications in predisposing aging women to behavioral/psychiatric problems.

PMID- 9657082
TI  - Effects of central nervous system polypharmacy on falls liability in community
      dwelling elderly.
AB  - BACKGROUND: While central nervous system (CNS) active medications such as
      psychotropics and narcotic analgesics have been implicated in contributing to
      falls in older adults, the combined effect of multiple CNS-active medications has
      not been investigated. The purpose of this study was to examine the influence, in
      community-dwelling elderly, of (1) taking multiple CNS-active medications on fall
      liability and (2) individual classes of CNS-active medications (using discrete
      drug classification) on the risk of falls after controlling for important
      confounders--age, mobility, cognition and depression. METHODS: 305 community
      dwelling male veterans (age: 70-104) were screened at study entry for mobility,
      cognition and depression. CNS-active medications were categorized as
      benzodiazepines, other sedative-hypnotics, neuroleptics, tricyclic
      antidepressants, and opioid analgesics. Subjects were prospectively followed for
      6 months to monitor falls; at the end of this time period, subjects were
      classified as fallers (at least one fall) or nonfallers. The relationship between
      CNS-active drug use and falls was examined using multivariable analyses. RESULTS:
      The risk of falls was significantly greater in CNS-active medication users as
      compared with nonusers. Adjusted odds ratio for one CNS-active drug was 1.54 (95%
      confidence interval 1.07-2.22) and for two or more agents 2.37 (95% confidence
      interval 1.14-4.94). CONCLUSIONS: In community-dwelling elderly, the use of
      multiple CNS-active medications is associated with enhanced falls liability, over
      and above the use of one CNS-active drug alone. This apparent dose-response
      relationship provides support for causality.

PMID- 9657083
TI  - Effects of age on gastric alkaline and nonparietal fluid secretion in humans.
AB  - Little is known about the effect of age on gastric alkaline and nonparietal
      secretion. Using a previously validated technique, we prospectively measured
      gastric HCO3- and nonparietal volume secretion, as well as secretion of H+, Na+,
      K+, and Cl-, in 114 healthy human beings over a wide age range (18-82 years).
      Each subject had normal oxyntic mucosal histology, was on no medication known to
      affect gastric secretion, and was studied under both basal (fasting) conditions
      and following stimulation of gastric H+ secretion by pentagastrin. There was a
      significant (p < 0.05) decline in gastric HCO3-, Na+, and nonparietal fluid
      secretion with advancing age, but not in H+, K+, Cl- or parietal fluid secretion.
      As a consequence of reduced gastric HCO3- and nonparietal fluid secretion, mean
      H+ concentrations in gastric juice increased significantly with advancing age.
      Thus, in healthy subjects with normal gastric histology, advancing age was
      associated with a significant decline in gastric HCO3-, Na+, and nonparietal
      fluid secretion, resulting in an increase in gastric acidity (H+ concentration).

PMID- 9657084
TI  - Effect of short-term recombinant growth hormone administration on plasma
      lipoproteins in elderly adults.
AB  - To characterize the effects of recombinant human growth hormone (rhGH) on plasma
      lipids and lipoproteins, rhGH was administered daily at a dose of 40
      micrograms.kg-1 (Genentech) for 14 days in 7 healthy elderly male (67.4 +/- 1.9
      years, 75.8 +/- 2.6 kg) adults. Six other healthy males (63.9 +/- 0.7 years, 77.8
      +/- 3.8 kg) served as concurrent controls. Total plasma cholesterol (TC),
      triglycerides (TG), very-low-density lipoprotein-cholesterol, low-density
      lipoprotein-cholesterol, high-density lipoprotein-cholesterol, very-low-density
      lipoprotein-TG (VLDL-TG) and apolipoprotein AI and apolipoprotein B were
      determined after an overnight fast before and after the 14-day period of rhGH
      administration. Subcutaneous rhGH administration was physiologically effective,
      as shown by a threefold increase in insulin-like growth factor-I (from 110.8 +/-
      8.2 to 355.5 +/- 41.6 ng.ml-1; p < 0.05). Plasma fasting insulin also increased
      from 38.0 +/- 6.5 to 129.9 +/- 43.8 mumol.l-1 (p < 0.05) at the end of the 14
      days of rhGH treatment. With respect to plasma lipid/lipoprotein changes, rhGH
      administration increased plasma TG levels (from 1.5 +/- 0.3 to 2.2 +/- 0.4 mmol.l
      1; p < 0.05) and VLDL-TG (from 1.1 +/- 0.3 to 1.8 +/- 0.4 mmol.l-1; p < 0.05),
      but did not change TC (from 5.0 +/- 0.4 to 5.2 +/- 0.3 mmol.l-1) or any other
      lipid/lipoprotein variables measured. No significant lipid changes were noted in
      the control group over the 14-day period. These data suggest that short-term rhGH
      treatment significantly alters plasma variables of TG profile, perhaps by
      altering metabolic parameters (i.e. synthesis and/or clearance rates) of VLDL
      metabolism.

PMID- 9657085
TI  - Risk factors for major injurious falls among the home-dwelling elderly by
      functional abilities. A prospective population-based study.
AB  - BACKGROUND: In order to identify the risk factors essential for preventing major
      injurious falls, the associations between injurious falls and certain factors
      were assessed among disabled and independent elderly, respectively, who had
      fallen during a 2-year period. METHODS: A prospective population-based study was
      conducted in five rural northern Finnish municipalities. The series consisted of
      all inhabitants aged 70 years or over, initially 979 persons. During a 2-year
      follow-up period, all injurious falls were recorded on the basis of telephone
      contacts, diary reporting and a review of the medical records of the
      participants. RESULTS: Thirty percent of the subjects having fallen sustained a
      major injury. The multivariate model applied to the disabled elderly showed the
      following variables to be related to a high risk for major injurious falls:
      divorced, widowed or unmarried marital status (odds ratio = 2.2), a low body mass
      index (odds ratio = 3.1), incomplete step continuity (odds ratio = 2.2), poor
      distant visual acuity (odds ratio = 2.3) and the use of long-acting
      benzodiazepines (odds ratio = 2.4). Among the independent elderly, the risk of a
      fall resulting in major injury was high among the subjects who had peripheral
      neuropathy (odds ratio = 2.5) or were suffering from insomnia (odds ratio = 4.1).
      CONCLUSIONS: The risk factors for major injuries in fall occurrences differ
      between the disabled and independent elderly. Preventive measures should be
      targeted according to the disabilities of the population.

PMID- 9657086
TI  - Effects of low-impact, moderate-intensity exercise training with and without
      wrist weights on functional capacities and mood states in older adults.
AB  - This study examined the effects of low-impact, moderate-intensity exercise
      training with and without wrist weights (0.68 kg.wrist-1) on functional
      capacities and mood states in older adults (age 68.6 +/- 5.6, mean +/- SD).
      Twenty-three senior citizens residing in the community were randomly assigned to
      wrist weight (WW; n = 12) and no-wrist weight (NW; n = 11) exercise groups while
      11 matched subjects served as non-exercise controls (NE). Exercise training was
      performed for 10 weeks, 3 days/week, for 60 min/session and consisted of low
      impact aerobic dance (50-70% of maximal heart rate) combined with exercises to
      promote muscular fitness, flexibility, and balance. Before and after the
      intervention, each participant's aerobic fitness, muscular strength, flexibility,
      static and dynamic balance, skinfold thickness, and psychological mood states
      were assessed under standardized testing conditions. Exercise training resulted
      in significant improvements in peak oxygen uptake, lower extremity muscle
      strength, and psychological vigor (p < 0.05) but did not affect other fitness
      components (p > 0.05). There were no differences between the WW and NW exercise
      groups for any of the same variables studied (p > 0.05). No significant pre- to
      post-test changes were found for the NE control group (p > 0.05). It is concluded
      that 10 weeks of low-impact, moderate-intensity exercise training of the type
      that can be considered well-rounded in nature provides a sufficient stimulus to
      augment aerobic fitness, beneficially affects leg strength, and increases
      feelings of vigor in older adults. The present observations indicate that the use
      of light wrist weights has no beneficial or adverse effects on the measured
      training outcomes.

PMID- 9657087
TI  - Deficiency of the growth hormone-insulin-like growth factor-I axis potentially
      involved in age-related alterations in body composition.

PMID- 9657088
TI  - Hepatocyte death in hepatocarcinogenesis.

PMID- 9657089
TI  - Chronic cholestasis in rats induces anhedonia and a loss of social interest.
AB  - Central fatigue commonly occurs in patients with primary biliary cirrhosis (PBC)
      and correlates closely with depression, and cholestatic rats exhibit central
      fatigue. Therefore, we undertook a series of experiments in both rats with
      cholestasis caused by bile duct resection (BDR) and sham-resected controls (15
      days after surgery) to determine if experimental cholestasis is associated with
      symptoms of depression that can be modeled in rats, namely anhedonia (loss of
      pleasure) and the loss of social interest. BDR rats exhibited significant
      anhedonia compared with sham controls as indicated by a loss in their preference
      for consuming a saccharin solution, a highly desirable drink for rats.
      Furthermore, social interest was examined by determining the time BDR or sham
      rats spent investigating a juvenile rat in an open-field apparatus compared with
      the time spent on nonsocial behaviors. BDR rats exhibited significantly reduced
      time spent in social investigation and significantly more time in nonsocial
      behaviors than did sham rats. Major depression in humans is often associated with
      elevated circulating glucocorticoid levels and impaired glucocorticoid feedback.
      Therefore, we measured these parameters in BDR and sham rats and found a striking
      elevation in circulating glucocorticoid levels in BDR compared with sham animals.
      However, elevated circulating glucocorticoid levels in BDR rats suppressed
      normally in response to exogenous dexamethasone, indicating intact glucocorticoid
      feedback control at the pituitary level in BDR rats. In summary, we have
      identified behaviors in cholestatic rats that are consistent with those seen in
      depression.

PMID- 9657090
TI  - Hepatic bile versus gallbladder bile: a comparison of protein and lipid
      concentration and composition in cholesterol gallstone patients.
AB  - Many studies have demonstrated that gallbladder bile (but not hepatic bile) of
      animals or patients with cholesterol gallstones contains higher protein
      concentrations than does gallbladder bile of control patients without stones or
      with pigment stones. The underlying defect has not been elucidated. To establish
      whether there is net production or net absorption/degradation of protein by
      gallbladder epithelium for different classes of protein, paired samples of
      hepatic and gallbladder bile were obtained from fourteen patients with
      cholesterol gallstones during elective cholecystectomy. In these paired samples,
      lipid and protein composition were determined. To obtain the concentration ratio
      (CR) of protein and lipid, its concentration in the gallbladder was divided by
      the concentration determined in the paired hepatic bile sample. The CR of bile
      salts was used as a parameter for water absorption in the gallbladder. Of the
      biliary proteins that were determined only mucin, albumin, immunoglobulin (Ig) G,
      and aminopeptidase N appeared to increase in the gallbladder from another cause
      than water absorption. A strong correlation was found between mucin, albumin, and
      IgG. Haptoglobin, alpha1-acid glycoprotein, IgM, and IgA appeared to be absorbed
      by gallbladder epithelium in the majority of patients. In cholesterol gallstone
      patients, total protein concentration in gallbladder bile of cholesterol
      gallstone patients is increased when compared with hepatic bile. The increase in
      protein concentration cannot be explained for all bile samples solely by water
      absorption. In this study we show that the defect is largely caused by a
      selective increase in albumin, mucin, and IgG. All other proteins which were
      investigated are taken up by the gallbladder.

PMID- 9657091
TI  - The diagnostic and predictive value of ascites nitric oxide levels in patients
      with spontaneous bacterial peritonitis.
AB  - Nitric oxide (NO) is a messenger molecule involved in pathogen suppression.
      Cirrhosis is characterized by an increased risk for infections, including
      spontaneous bacterial peritonitis (SBP). The role of NO in the infections that
      develop in cirrhosis has not been clearly established. The aim of this study was
      to investigate the utility of measuring ascites NO in the diagnosis of SBP and/or
      in determining the predisposition of cirrhotic patients to develop this
      infection. Nitric oxide metabolites (nitrites + nitrates [NOx]) were measured by
      chemiluminescence in 105 ascites samples obtained from 87 cirrhotic patients and
      in 87 simultaneously obtained serum samples. Ascites NO levels were not
      significantly different among ascites from patients with SBP (n = 39; median, 48
      micromol/L), patients with sterile ascites (n = 54; median, 42 micromol/L), and
      samples obtained after patients with SBP had been treated (n = 12; median, 62
      micromol/L). No differences in ascites NO levels were observed between culture
      positive and culture-negative peritonitis. Among 50 patients with sterile ascites
      on initial paracentesis, 7 patients developed peritonitis during follow-up; no
      differences in baseline NO levels were observed between patients who developed
      peritonitis (median, 46 micromol/L) and those who did not (median, 41
      micromol/L). Among patients with SBP, mortality was significantly higher in those
      with NO levels >60 micromol/L. A very significant direct correlation was found
      between ascites and serum NO levels (r2 = .86). In conclusion, ascites NO levels
      in cirrhotic patients are not useful either to diagnose or to determine
      predisposition to SBP. Rather, ascites NO levels reflect serum levels, are higher
      in cirrhotic patients with more severe liver disease, and may be a useful
      prognostic marker.

PMID- 9657092
TI  - Development of pseudointima and stenosis after transjugular intrahepatic
      portasystemic shunts: characterization of cell phenotype and function.
AB  - The clinical utility of transjugular intrahepatic portasystemic shunts (TIPS) is
      frequently complicated by the ingrowth of tissue into the stent lumen, causing
      stent stenosis. These studies were undertaken to define the cellular and matrix
      components of the pseudointima, define the phenotype and function of the
      mesenchymal cells in the pseudointima and maintain them in culture, and to study
      the differences between stenotic and nonstenosed stents. A total of 35 stents
      were evaluated. TIPS pseudointima were examined histologically, by
      immunohistochemistry and in situ hybridization to determine the cellular and
      connective tissue constituents. Mesenchymal cells were grown from tissue within
      the TIPS and around it, and their phenotype was studied and compared with control
      smooth muscle cells and fibroblasts. Masson's trichrome staining of histological
      sections demonstrated that TIPS tissue was composed of collagen and palisades of
      mesenchymal cells and was lined by an endothelium. Immunostaining demonstrated
      strong and uniform alpha-smooth muscle staining in TIPS mesenchymal cells and
      peri-TIPS cells. Type I procollagen mRNA expression was demonstrated in
      mesenchymal cells in and around the stent by in situ hybridization. TIPS
      mesenchymal cells secreted less radiolabeled fibronectin, and far more type III,
      relative to type I, collagen compared with peri-TIPS cells. TIPS cells also
      expressed high levels of type III procollagen mRNA compared with peri-TIPS cells.
      There was no difference between stenotic stents and nonstenosed stents with
      respect to clinical features, time from stenting, gross morphology, histology,
      presence of bile fistulae, and cell phenotype. However, smooth muscle cells (SMC)
      from stenotic stents demonstrated both greater cell proliferation and collagen I
      and III secretion compared with those from nonstenosed stents. These data
      demonstrate that TIPS stenosis results from an accumulation of collagen and
      proliferation of SMC within the stent lumen.

PMID- 9657093
TI  - Optimal timing of liver transplantation for primary biliary cirrhosis.
AB  - In 1989, we reported on the efficacy of liver transplantation in primary biliary
      cirrhosis (PBC) by demonstrating that the actual patient survival following
      transplantation was significantly better than without transplantation as
      predicted by a mathematical survival model ("Mayo natural history model"). Our
      aim in this investigation was to determine an optimal time to perform liver
      transplantation in PBC. One hundred forty-three patients with PBC undergoing
      liver transplantation were followed prospectively. Disease severity was measured
      immediately before transplantation by a summary score ("risk score") used in the
      Mayo natural history model, namely age, bilirubin, albumin, prothrombin time, and
      the presence or absence of edema. Proportional hazards analyses were performed
      assessing patient survival following transplantation. The influence of disease
      severity immediately pretransplantation on resource utilization for liver
      transplantation was assessed. Compared with our report in 1989, liver
      transplantation was performed at an earlier stage of disease (e.g., median risk
      score: 7.5 vs. 8.3; P < .01). Following transplantation, patient survival
      probabilities at 1, 2, and 5 years were 93%, 90%, and 88%, respectively. In the
      proportional hazards analysis, the risk of death following transplantation
      remained low until reaching a risk score of 7.8. In contrast, risk scores greater
      than 7.8 were associated with a progressively increased mortality. Resource
      utilization measured by the days in the intensive care unit (ICU) and hospital
      and the requirement for intraoperative blood transfusions was significantly
      greater in recipients who had higher risk scores before transplantation. Our data
      suggest that an optimal timing for liver transplantation, as determined by
      patient survival and resource utilization, appears to be at a risk score around
      7.8 in patients with PBC.

PMID- 9657094
TI  - Increased cerebrovascular resistance in cirrhotic patients with ascites.
AB  - Studies assessing regional hemodynamics in patients with cirrhosis and ascites
      have shown vasodilation in the splanchnic circulation and vasoconstriction in the
      renal circulation and in the brachial and femoral artery vascular territories.
      The aim of this study was to assess the cerebral vascular resistance in cirrhotic
      patients with ascites. The resistive index in the middle cerebral artery (an
      index of the cerebral vascular resistance) and in a renal interlobar artery were
      measured by Doppler ultrasonography in 7 healthy subjects: 13 patients with
      compensated cirrhosis and 24 patients with ascites (13 with renal failure). The
      arterial blood pressure and the activity of the renin-angiotensin and sympathetic
      nervous systems, as estimated by plasma renin activity and plasma norepinephrine
      concentration, respectively, were also measured. The resistive index in the
      middle cerebral artery was significantly increased in patients with ascites (0.68
      +/- 0.05, mean +/- SD) as compared with patients without ascites (0.60 +/- 0.01,
      P < .05) and with healthy patients (0.52 +/- 0.01, P < .01). Renal resistive
      index was also increased in patients with ascites (0.77 +/- 0.01) compared with
      the other two groups (0.68 +/- 0.02 and 0.62 +/- 0.00, respectively; P < .001).
      The resistive index in the middle cerebral artery showed a direct correlation
      with renal resistive index (r = .73, P < .01), plasma renin activity (r = .61, P
      < .01), and norepinephrine (r = .53, P < .01). The resistive index in the middle
      cerebral artery showed an inverse correlation with mean arterial pressure (r = 
      .45, P < .01). These results indicate that in patients with cirrhosis and ascites
      there is a cerebral vasoconstriction which is probably related with the arterial
      hypotension and the overactivity of vasoconstrictor systems.

PMID- 9657095
TI  - Subclinical hepatic encephalopathy impairs daily functioning.
AB  - Subclinical hepatic encephalopathy (SHE) is assumed to have a negative effect on
      patients' daily functioning; therefore, treatment is recommended. However, no
      studies have been performed that document the clinical relevance of SHE. We
      performed a study in which the prevalence of SHE was determined in 179
      outpatients with cirrhosis using two psychometric tests (Number Connection Test
      Part A [NCT-A] and the Digit Symbol Test [DGT]) and automated analysis of the
      electroencephalogram (EEG). SHE was defined by the presence of at least one
      abnormal psychometric test and/or abnormal slowing of the EEG. The influence of
      cirrhosis and SHE on patients' daily functioning was assessed using the Sickness
      Impact Profile (SIP) questionnaire. The distribution of SIP scores of the
      patients with cirrhosis differed from the reference scores of the general
      population. Patients with cirrhosis and SHE (n = 48) reported significantly more
      impairment in all 12 scales of the SIP, in the psychosocial subscore, the
      physical subscore, as well as in the total SIP score, compared with cirrhotic
      patients without SHE (n = 131). Multivariate analysis taking into account
      severity of liver disease (Child-Pugh score), presence of varices, and alcoholic
      etiology, showed that SHE independently was related to a diminished total SIP
      score. The reproducibility of the SIP was high when the test was repeated after a
      3-month period. We conclude that SHE implies impaired daily functioning and
      warrants attempts at treatment.

PMID- 9657096
TI  - Sorbitol as a test substance for measurement of liver plasma flow in humans.
AB  - The objective of this study was to evaluate whole-body removal kinetics of
      sorbitol, the use of extrarenal sorbitol clearance to estimate hepatic plasma
      flow in humans, and to compare measurements of liver flow by Fick's principle
      using either indocyanine green (ICG) or sorbitol. A sorbitol bolus (5 mmol/kg)
      was given intravenously to 6 controls for determination of sorbitol elimination
      capacity (SEC) and distribution volume, V(sorb)d. Sorbitol infusion (287
      micromol/ min) was given to 17 liver patients and 11 controls. Extrarenal
      sorbitol clearance (V(sorb)x was calculated as infusion rate (corrected for renal
      excretion and accumulation in V(sorb)d) divided by arterial concentration. Liver
      flow (Q(ICG)) was calculated from the ICG infusion and arterial and hepatic
      venous ICG concentrations by Fick's principle. Average SEC was 73
      micromol/min/kg, V(sorb)d was 0.16 L plasma per kilogram, and in vivo V(sorb)d
      was 3 mmol/L. Renal sorbitol excretion rate was 0.03 to 0.31 of infusion rate.
      Extrahepatic extrarenal removal was not significantly different from zero but
      varied considerably. Hepatic extraction fraction of sorbitol, (E(sorb)), measured
      by liver vein catheterization, was 0.35 to 1.04 (median, 0.86) in cirrhotic
      patients and 0.90 to 0.98 (0.86) in controls. The requirements for using
      Cl(sorb)x as an estimate of Q(ICG) was not violated by the data in controls,
      Cl(sorb)x/Q(ICG) 0.70 to 1.55 [median, 1.08]), whereas there was a systematic
      underestimation in cirrhotic patients (0.72-1.08 [0.85]). Liver flow calculated
      by Fick's principle using either sorbitol or ICG agreed well. E(sorb) > E(ICG) in
      each individual except one. Curvilinear relationship between E(sorb) and E(ICG)
      was in agreement with different kinetic parameters for sorbitol and ICG, and did
      not require additional assumption of intrahepatic shunts.

PMID- 9657097
TI  - A novel human tumor necrosis factor alfa mutein, F4614, inhibits in vitro and in
      vivo growth of murine and human hepatoma: implication for immunotherapy of human
      hepatocellular carcinoma.
AB  - Although treatment for hepatocellular carcinoma (HCC) has recently improved, most
      patients still relapse and die from this disease. The development of new
      therapeutic and preventive strategies for HCC is, therefore, required. A novel
      mutant protein (mutein) of human tumor necrosis factor alfa (TNF-alpha mutein
      F4614, 1SSSRGDSD... 29V ... 155L) was developed to decrease several adverse
      effects of TNF-alpha. F4614 is known to lack hypotensive effects of human TNF
      alpha without losing its anti-tumor effect in mice transplanted with Meth-A
      sarcoma. Our study investigated the anti-tumor effects of F4614 against hepatoma
      cells in vitro and in vivo. F4614 significantly inhibited growth of all four
      tumor cells in vitro. A murine hepatoma cell line, MH134, when incubated in the
      presence of F4614, exhibited upregulation of surface major histocompatibility
      complex (MHC) class-I, intercellular adhesion molecule-1 (ICAM-1) and B7-1
      molecules, and a decreased proportion of cells in the G2/M phase of the cell
      cycle. In addition, F4614 induced apoptosis in a significant number of MH134
      cells. TNF-alpha and F4614 (5 microg/mouse daily for 5 days) showed similar anti
      tumor activities in syngeneic MH134-bearing mice and heterogeneic PLC/PRF/5
      bearing athymic nude mice. Intratumoral injection of F4614 or TNF-alpha was more
      effective than intravenous injection. Immunohistochemical analysis of the tumors
      treated by F4614 revealed that tumors were surrounded with a large number of Mac
      1+ cells and a small number of CD4+ and CD8+ T cells; that suggests that
      intratumoral injection of F4614 elicited host immunoreactions. Thus, F4614 may be
      a new strategy for immunotherapy of HCC.

PMID- 9657098
TI  - Expression of vascular endothelial growth factor in human hepatocellular
      carcinoma.
AB  - Vascular endothelial growth factor (VEGF) is thought to take an important role in
      tumor angiogenesis. The present study examined VEGF expression
      immunohistochemically in hepatocellular carcinomas (HCCs) in various histological
      grades and sizes. In HCCs that were composed of cancerous tissues of single
      histological grade, VEGF expression was the highest in well-differentiated HCCs,
      followed by moderately differentiated HCCs, and then poorly differentiated HCCs.
      VEGF positivity gradually decreased with the increase in tumor size. In the
      nodules larger than 3.0 cm, 36.8% were VEGF-negative. In HCCs consisting of
      cancerous tissues of two different histological grades, the expression was less
      intensive in the higher-grade HCC component. VEGF was not expressed in
      sarcomatous areas, while VEGF was expressed in the surrounding HCC tissues. The
      expression was also remarkable in the noncancerous tissues in which inflammatory
      cell infiltration was apparent. VEGF expression was also examined in six HCC cell
      lines. In reverse-transcription polymerase chain reaction (RT-PCR) analysis,
      expressions of the two secretion types (VEGF121 and VEGF165) were the highest.
      Thus, VEGF protein in culture supernatant was measured by using enzyme-linked
      immunosorbent assay (ELISA) with or without inflammatory cytokines, i.e.,
      interleukin (IL)-1beta, interferon (IFN)-alpha, IFN-gamma, and tumor necrosis
      factor (TNF)-alpha; and growth factors, i.e., epidermal growth factor (EGF),
      platelet-derived growth factor (PDGF)-BB, basic fibroblast growth factor (bFGF),
      and transforming growth factor (TGF)-alpha. As a result, secretion of VEGF from
      the cell lines was upregulated at various degrees. Based on these findings, VEGF
      expression in HCC tissues was thought to be related to the histological grade.
      The findings also indicate that various cytokines and growth factors could
      cooperatively act to enhance VEGF expressions in HCC.

PMID- 9657099
TI  - Genomic fluidity is a necessary event preceding the acquisition of tumorigenicity
      during spontaneous neoplastic transformation of WB-F344 rat liver epithelial
      cells.
AB  - The genomic evolution of a cohort of WB-F344 rat liver epithelial cell lineages
      undergoing spontaneous neoplastic transformation was followed to define the
      mechanistic relationship between genomic instability and progression to the
      neoplastic phenotype. Eighteen independent populations of WB-F344 cells
      (initiated from a single diploid-founding population) were subjected to 12 cycles
      of selective growth at confluent cell density, and cellular DNA contents were
      measured after each selection cycle. Flow cytometry demonstrated significant
      gains in the amount of G1 DNA after selection cycles 3, 6, and 7 in 44% (8 of
      18), 89% (16 of 18), and 39% (7 of 18) of the cell populations, respectively. All
      populations subsequently lost DNA and returned to a diploid or pseudo-diploid DNA
      content within 1 to 2 selection cycles after the appearance of an increased DNA
      content. Additionally, appearance and subsequent disappearance of aneuploid or
      tetraploid subpopulations was observed in 11% (2 of 18) and 83% (15 of 18) of the
      experimental lineages, respectively. Although perturbations of G1 DNA content
      were apparent as early as selection cycle 3, at least 8 cycles of selective
      growth were required for the acquisition of tumorigenicity. While the independent
      lineages demonstrated significant fluctuations in G1 DNA content between
      selection cycles 3 and 8, the majority (11 of 13) of the populations contained a
      diploid or pseudo-diploid DNA content at the time tumorigenicity was expressed.
      Genomic instability preceded the acquisition of tumorigenic potential in rat
      liver epithelial cells subjected to selective growth conditions of maintenance at
      confluence, and may be required for its expression.

PMID- 9657100
TI  - Allelic imbalance of insulin-like growth factor II gene expression in cancerous
      and precancerous lesions of the liver.
AB  - Allelic imbalance of the insulin-like growth factor II (IGF II) gene expression
      is often seen in hepatocellular carcinoma (HCC). To investigate the role of
      allelic imbalance in hepatocarcinogenesis, we have studied allelic expression
      status of the IGF II gene in dysplastic nodules, which are precancerous lesions
      of HCC, as well as in HCCs of different histological grade, and the influence of
      the allelic imbalance on IGF II gene expression has also been examined. Allelic
      imbalance was observed in 3 of 7 dysplastic nodules, in 7 of 9 well
      differentiated HCCs, and in 8 of 9 moderately differentiated HCCs. IGF II gene
      expression level, which was studied by a semiquantitative reverse-transcriptase
      polymerase chain reaction (RT-PCR), was significantly higher (3.6-fold) in the
      dysplastic nodules than the control livers, but a significant increase in the IGF
      II gene expression was not observed in well- and moderately differentiated HCCs
      as compared with the control livers. These results demonstrate that the allelic
      imbalance of the IGF II gene expression is seen in the early stage (precancerous
      lesions) of hepatocarcinogenesis. Association of the allelic imbalance with an
      increased expression of the IGF II gene in the precancerous lesions might suggest
      a possible involvement of an IGF II autocrine loop in the pathogenesis of these
      lesions.

PMID- 9657101
TI  - Microsatellite instability and loss of heterozygosity at DNA mismatch repair gene
      loci occurs during hepatic carcinogenesis.
AB  - DNA mismatch repair is an important mechanism involved in maintaining the
      fidelity of genomic DNA. Defective DNA mismatch repair is implicated in a variety
      of gastrointestinal and other tumors; however, its role in hepatocellular
      carcinoma (HCC) has not been assessed. Formalin-fixed, paraffin-embedded archival
      pathology tissues from 46 primary liver tumors were studied by microdissection
      and microsatellite analysis of extracted DNA to assess the degree of
      microsatellite instability, a marker of defective mismatch repair, and to
      determine the extent and timing of allelic loss of two DNA mismatch repair genes,
      human Mut S homologue-2 (hMSH2) and human Mut L homologue-1 (hMLH1), and the
      tumor suppressor genes adenomatous polyposis coli gene (APC), p53, and DPC4.
      Microsatellite instability was detected in 16 of the tumors (34.8%). Loss of
      heterozygosity at microsatellites linked to the DNA mismatch repair genes, hMSH2
      and/or hMLH1, was found in 9 cases (19.6%), usually in association with
      microsatellite instability. Importantly, the pattern of allelic loss was uniform
      in 8 of these 9 tumors, suggesting that clonal loss had occurred. Moreover, loss
      at these loci also occurred in nonmalignant tissue adjacent to 4 of these tumors,
      where it was associated with marked allelic heterogeneity. There was relatively
      infrequent loss of APC, p53, or DPC4 loci that appeared unrelated to loss of
      hMSH2 or hMLH1 gene loci. Loss of heterozygosity at hMSH2 and/or hMLH1 gene loci,
      and the associated microsatellite instability in premalignant hepatic tissues
      suggests a possible causal role in hepatic carcinogenesis in a subset of
      hepatomas.

PMID- 9657102
TI  - Collagen XVIII is localized in sinusoids and basement membrane zones and
      expressed by hepatocytes and activated stellate cells in fibrotic human liver.
AB  - Type XVIII collagen is a recently discovered nonfibrillar collagen associated
      with basement membranes in mice and expressed at high levels in human liver. We
      studied the origin, distribution, and RNA levels of type XVIII collagen in normal
      and fibrotic human livers by in situ hybridization, immunohistochemistry, and
      Northern and dot blots and compared procollagen alpha1(XVIII) RNA levels with
      those of procollagen alpha1(IV) and laminin gamma1, the two major components of
      liver basement membranes. In normal liver, type XVIII collagen was heavily
      deposited in perisinusoidal spaces and basement membrane zones. The major source
      of type XVIII collagen was hepatocytes and, to a lesser extent, endothelial,
      biliary epithelial, and vascular smooth muscle cells and peripheral nerves. In
      cirrhosis, type XVIII collagen formed a thick deposit along capillarized
      sinusoids. Grain counts after in situ hybridization showed myofibroblasts to
      increase their expression 13-fold in active and twofold in quiescent fibrosis,
      whereas hepatocytes increased their expression only twofold in both active and
      quiescent fibrosis. Activated stellate cells in vitro expressed type XVIII
      collagen at high levels. These data indicate that type XVIII collagen is a
      component of the perisinusoidal space and is associated with basement membrane
      remodeling. Hepatocytes and activated stellate cells are important sources of
      type XVIII collagen in normal and fibrotic liver respectively, which suggests
      tissue-specific regulation of its expression.

PMID- 9657103
TI  - Interleukin-8 and hIRH (SDF1-alpha/PBSF) mRNA expression and histological
      activity index in patients with chronic hepatitis C.
AB  - Recombinant human intercrine reduced in hepatomas (hIRH)/stromal cell-derived
      factor 1 (SDF1-alpha)/pre-B-cell growth-stimulating factor (PBSF), a new
      chemokine, exhibits an in vitro chemotaxis to neutrophils and a mixed in vivo
      chemotactic activity to neutrophils, lymphocytes, and monocytes in a rat
      intradermal injection model. We have investigated the messenger RNA (mRNA)
      expression of interleukin-8 (IL-8) and hIRH, in chronic hepatitis C of differing
      severity. Levels of expression of IL-8 and hIRH mRNA obtained from 37 human liver
      biopsy samples were measured by reverse-transcription and semiquantitative
      polymerase chain reaction (RT-PCR) amplification. We examined the correlation
      between mRNA expression and components of the histological activity index (HAI).
      Patients with HAI > or = 8 had a significantly higher corrected IL-8 mRNA
      expression ratio (0.24 +/- 0.13 [mean +/- SD]; n = 20) than those with HAI < or =
      7 (0.05 < or = 0.03; n = 17; P < .0001). Additionally, IL-8 mRNA expression was
      strongly associated with the severity of portal inflammation (PI) (high PI vs.
      low PI, 0.22 +/- 0.14 vs. 0.05 +/- 0.04; P < .0001) and with the presence of bile
      duct lesions (0.29 +/- 0.15 vs. 0.11 +/- 0.1; P < .01). In contrast, hIRH mRNA
      expression was not associated with the total HAI, any components of the HAI, or
      bile duct inflammation or injury. These results suggest that hIRH, although
      having the -CXC-, alpha chemokine motif, and exhibiting in vivo and in vitro
      inflammatory activity as does IL-8, plays a different role from IL-8 in hepatic
      inflammation and injury. IL-8 expression is directly associated with inflammation
      in patients with chronic hepatitis C, while hIRH expression does not correlate
      with histopathological severity of inflammation.

PMID- 9657104
TI  - Protein phosphatase inhibition in normal and keratin 8/18 assembly-incompetent
      mouse strains supports a functional role of keratin intermediate filaments in
      preserving hepatocyte integrity.
AB  - The function and regulation of keratin 8 (K8) and 18 (K18), intermediate filament
      (IF) proteins of the liver, are not fully understood. We employed the liver
      damage induced by microcystin-LR (MC-LR), a liver-specific inhibitor of type-1
      and type-2A protein phosphatases, in normal and in keratin assembly-incompetent
      mouse strains as a model to elucidate the roles of IF phosphorylation in situ.
      The mouse strains used were wild-type (wt) mice and mice with abnormal filament
      assembly, caused by a targeted null mutation of the K8 gene or caused by
      expression of a point-mutated dominant negative human K18. In vivo 32P-labeled wt
      mice, subsequently injected with a lethal dose of MC-LR, showed
      hyperphosphorylation, disassembly, and reorganization of K8/K18, in particular
      K18, indicating high phosphate turnover on liver keratins in situ. At lethal
      doses, the keratin assembly-incompetent mice displayed liver lesions faster than
      wt mice, as indicated histopathologically and by liver-specific plasma enzyme
      elevations. The histological changes included centrilobular hemorrhage in all
      mouse strains. The assembly-incompetent mice showed a marked vacuolization of
      periportal hepatocytes. Indistinguishable MC-LR-induced reorganization of
      microfilaments was observed in all mice, indicating that this effect on
      microfilaments is not dependent on the presence of functional K8/K18 networks. At
      sublethal doses of MC-LR, all animals had the same potential to recover from the
      liver damage. Our study shows that K8/K18 filament assembly is regulated in vivo
      by serine phosphorylation. The absence or occurrence of defective K8/K18
      filaments render animals more prone to liver damage, which supports the
      previously suggested roles of keratin IFs in maintenance of structural integrity.

PMID- 9657105
TI  - Effects of diosgenin, a plant-derived steroid, on bile secretion and
      hepatocellular cholestasis induced by estrogens in the rat.
AB  - Increased biliary secretion of cholesterol and lipid vesicles (unilamellae and
      multilamellae) induced by diosgenin (D), a plant-derived steroid, has
      cytoprotective effects in the rat liver subjected to obstructive cholestasis. In
      this study, our aims were to investigate the following: 1) the effects of D on
      the bile secretory process and on the cholestasis induced by estradiol-17beta
      (beta-D-glucuronide) (E17G) or 17 alpha-ethynylestradiol (E) administration; 2)
      whether the potentially protective effects of D are related to D-induced increase
      of biliary cholesterol and lipid lamellae; and 3) whether D has other effects
      capable of modifying specific bile secretory processes or preventing the
      cholestatic effects of estrogens. Rats were fed a standard ground chow (control
      group) or chow containing D for 6 days. E17G was administered i.v. to control and
      D-fed rats and bile flow, bile salt output, and alkaline phosphatase excretion
      were examined. 17alpha-E was administered from days 4 to 6 to rats fed standard
      chow or chow plus D for 6 days and different functional parameters of the bile
      secretory process as well as the ultrastructure of hepatocytes and histochemistry
      of alkaline phosphatase and Mg2+-adenosine triphosphatase (ATPase) were examined.
      D-treatment markedly increased cholesterol and lamellar structures in bile and
      attenuated the acute cholestatic effects of E17G. D-feeding prevented the
      decrease of taurocholate maximum secretory rate and the increase of biliary
      alkaline phosphatase and Ca2+,Mg2+-EctoATPase (EctoATPase) excretion, as well as
      the increase of cholesterol/ phospholipids ratio, alkaline phosphatase activity,
      and EctoATPase content in canalicular plasma membranes induced by E. D-feeding
      did not prevent E-induced decrease of basal bile flow, bile salt, cholesterol,
      and phospholipid secretory rates nor the decrease of Na+,K+-ATPase activity and
      Na+-taurocholate cotransporting polypeptide (Ntcp) content in isolated sinusoidal
      membranes. Cholestatic alterations of canalicular domain were apparent in E
      treated rats. D administration was also associated with changes of ultrastructure
      and histochemistry of hepatocytes. E-induced alterations in ultrastructure and
      acinar distribution and intensity of histochemical reaction of both enzymes were
      partially prevented by D-feeding. We conclude that D administration, in addition
      to inducing a marked increase of biliary cholesterol and lipid lamellar
      structures output, was associated to changes in hepatocyte morphology and plasma
      membrane composition, enzymes activity, and histochemistry. D-feeding attenuated
      the acute cholestatic effects of E17G. D-induced increase of bile cholesterol and
      lipid lamellae content was not apparent when D-fed rats received E. Despite this
      fact, D administration prevented some cholestatic effects of E, probably through
      different metabolic effects and/or direct membrane effects, not related to
      increased lipid lamellae excretion.

PMID- 9657106
TI  - Insulin resistance in cirrhosis: prolonged reduction of hyperinsulinemia
      normalizes insulin sensitivity.
AB  - Insulin resistance is present in nearly all patients with cirrhosis, but its
      etiology remains unknown. Chronic hyperinsulinemia has been suspected as a
      potential candidate, and we therefore tested the hypothesis that, in cirrhosis,
      prolonged reduction of the hyperinsulinemia restores insulin sensitivity. Whole
      body insulin sensitivity (euglycemic insulin-clamp technique), glucose turnover
      (6,6-2H2-glucose isotope dilution), glucose oxidation (indirect calorimetry), non
      oxidative glucose disposal, and fractional glycogen synthase activity in muscle
      (biopsies) were measured in eight clinically stable patients with cirrhosis
      before and at the end of a 4-day continuous subcutaneous infusion of the
      somatostatin-analogue octreotide (200 microg/24 h) designed to continuously
      reduce plasma insulin levels. Baseline data were compared with results obtained
      in healthy individuals matched for sex, age, and weight (n = 8). During the
      baseline (pre-octreotide) study, patients demonstrated a significant decrease in
      insulin-mediated glucose uptake compared with controls (5.75 +/- 0.21 vs. 7.98 +/
      0.84 mg/kg/min; P < .03), which was entirely accounted for by an impairment in
      non-oxidative glucose disposal (P < .04). Four-day infusion of octreotide to
      cirrhotic patients: 1) reduced postabsorptive and meal-stimulated plasma insulin
      levels by approximately 35% to 45% without significantly affecting glucose
      tolerance; 2) did not significantly alter plasma free fatty acids (FFA), growth
      hormone, and glucagon levels in the postabsorptive state and during the meal
      test; 3) normalized insulin-mediated whole-body glucose disposal (7.63 +/- 0.72
      mg/kg/min post-octreotide; P = not significant vs. control). Restoration of
      insulin-mediated glucose utilization was entirely caused by normalization of non
      oxidative glucose disposal; 4) was associated with a considerably more pronounced
      stimulation by insulin of the fractional glycogen synthase in muscle compared
      with pre-octreotide results (increment above baseline pre: 0.035 +/- 0.010 vs.
      post: 0.060 +/- 0.023 nmol/min/mg protein; P < .04). Fractional glycogen activity
      significantly correlated with non-oxidative glucose disposal during insulin
      infusion (r = .69; P < .03). Prolonged reduction of hyperinsulinemia for 96 hours
      in cirrhotic patients normalizes insulin-mediated glucose uptake and glycogen
      synthesis in muscle. We conclude that chronic hyperinsulinemia causes insulin
      resistance in cirrhosis.

PMID- 9657107
TI  - Initial heme uptake from albumin by short-term cultured rat hepatocytes is
      mediated by a transport mechanism differing from that of other organic anions.
AB  - Although it is known that circulating heme accumulates in liver cells, the
      process by which heme enters hepatocytes is only partly understood. Hemopexin and
      a putative hemopexin receptor on hepatocyte membranes may mediate the uptake
      process. However, whether there are sufficient hemopexin receptors on rat
      hepatocytes to account for the bulk of heme entering cells is unknown. It is
      likely that heme may be transferred directly from albumin with the help of a
      plasma membrane heme transporter. To clarify the transport mechanism of heme into
      liver cells, we studied the uptake by short-term cultured rat hepatocytes of 55Fe
      heme incubated with rat serum albumin. In these cells, the initial uptake of 55Fe
      heme at 37 degrees C was five- to eightfold higher than that at 4 degrees C,
      linear for at least 5 minutes, and saturable. The Km of heme uptake was 0.95 +/-
      0.27 micromol/L, and the Vmax was 0.12 +/- 0.01 pmol/min/mg protein (n = 3).
      Neither isosmotic substitution of sucrose for NaCl in the medium nor adenosine
      triphosphate (ATP) depletion, perturbations that are known to reduce uptake of
      bilirubin, sulfobromophthalein (BSP), and taurocholate, had any influence on 55Fe
      heme uptake. In addition, heme uptake was not reduced in the presence of a
      greater than 500-fold molar excess of BSP. These results indicate that
      hepatocytes take up heme by a process that is distinct from that of these other
      organic anions.

PMID- 9657109
TI  - The polarized hepatic human/rat hybrid WIF 12-1 and WIF-B cells communicate
      efficiently in vitro via connexin 32-constituted gap junctions.
AB  - Gap junction intercellular communication (GJIC) plays an essential role in the
      control of growth, differentiation, and functions of different tissues. The
      expression of connexins (Cxs), the structural proteins of gap junctions, is
      developmentally regulated and tissue-specific. In vivo hepatocytes express Cx32
      and Cx26. Most currently available in vitro hepatic cell systems express Cx43
      instead of the expected Cxs. This work analyzes the GJIC competence and Cx
      expression of the highly differentiated and polarized hepatoma-derived hybrid
      cell lines, WIF 12-1 and WIF-B. It shows (using two dye transfer assays) that
      both lines communicate efficiently and that the acquisition of GJIC competence
      precedes the formation of bile canaliculi. Interestingly, these cells communicate
      via Cx32 expression, whereas Cx26 and Cx43 are not expressed, as demonstrated by
      Western and Northern blotting, immunocytochemistry, and confocal microscopy. The
      human fibroblast W138 parent communicates via Cx43, whereas the rat hepatoma
      parent Fao and the subclone WIF 12-1 TGdelta, that has lost the human X
      chromosome, do not communicate, the expression of Cx32 being restricted to the
      mRNA in these two lines. The GJIC competence of WIF cells could thus result from
      the activation of the human X chromosome-linked Cx32 gene.

PMID- 9657108
TI  - Expression of cytosolic beta-glucosidase in guinea pig liver cells.
AB  - The cytosolic beta-glucosidase of mammalian liver has been implicated in the
      metabolic transformation of plant glycosides, such as vicine and amygdalin, which
      are associated with the development of toxic syndromes. We investigated which
      cell types express cytosolic beta-glucosidase in guinea pig liver, and
      characterized the contribution of this enzyme to the hydrolysis of aromatic
      glucosides in cultured cells and in tissue slices. Cytosolic beta-glucosidase was
      expressed in hepatocytes and not in Kupffer or endothelial cells as determined by
      enzyme-specific activity and Western blots of liver cell extracts. Intracellular
      beta-glucosidase activity was visualized using the fluorescent beta-glucosidase
      substrate, resorufin beta-D-glucoside, and shown to be caused by the cytosolic
      beta-glucosidase using the inhibitors, conduritol beta-epoxide and dinitrophenol
      2-deoxy-2-fluoro-beta-D-glucopyranoside (DNP2FGlc). Staining of fresh liver
      slices with resorufin beta-glucoside revealed that cytosolic beta-glucosidase is
      expressed in all hepatocytes, with no significant portal-central gradient. These
      data indicate that cytosolic beta-glucosidase is a hepatocyte-specific enzyme,
      and support the hypothesis that cytosolic beta-glucosidase in the liver functions
      to hydrolyze small glucosides absorbed by the intestine. Furthermore, toxic
      injury to cultured hepatocytes by CCl4 resulted in release of cytosolic beta
      glucosidase in parallel with the hepatocyte marker enzymes alanine transaminase
      and lactate dehydrogenase. This suggests that acute increases in serum levels of
      cytosolic beta-glucosidase in animal models of liver injury may reflect direct
      injury of hepatocytes.

PMID- 9657110
TI  - Lack of coordinate control of ferritin and transferrin receptor expression during
      rat liver regeneration.
AB  - Transferrin receptor (TfR) and ferritin, key proteins of cellular iron
      metabolism, are coordinately and divergently controlled by cytoplasmic proteins
      (iron regulatory proteins, IRP-1 and IRP-2) that bind to conserved mRNA motifs
      called iron-responsive elements (IRE). IRP, in response to specific stimuli (low
      iron levels, growth and stress signals) are activated and prevent TfR mRNA
      degradation and ferritin mRNA translation by hindering ferritin mRNA binding to
      polysomes. We previously found that, in regenerating liver, IRP activation was
      accompanied by increased TfR mRNA levels, but not by reduced ferritin expression.
      The basis for this unexpected behavior was investigated in the present study.
      Liver regeneration triggered by carbon tetrachloride (CCl4) stimulated by four-
      to fivefold the synthesis of both L and H ferritin chains. This increase was
      accompanied with a transcriptionally regulated twofold rise in the amount of
      ferritin mRNAs. Moreover, polysome-associated ferritin transcripts were fourfold
      higher in CCl4-treated animals than in control animals. Because RNA bandshift
      assays showed a fourfold increase in IRP-2 binding activity after CCl4
      administration, activated IRP in regenerating liver seemed unable to prevent
      ferritin mRNAs binding to polysomes. This was confirmed by direct demonstration
      in the wheat germ translation system that the efficiency of IRP as a
      translational repressor of a mRNA bearing an IRE motif in front of a reporter
      transcript is impaired in CCl4-treated rats in spite of an enhanced IRE-binding
      capacity. In conclusion, we show for the first time that the paradigm of
      coordinate and opposite control of ferritin and TfR by IRP is contradicted in
      liver regeneration. Under these circumstances, growth-dependent signals may
      activate ferritin gene transcription and at the same time hamper the ability of
      activated IRP-2 to repress translation of ferritin mRNAs, thus preserving for
      growing liver cells an essential iron-storage compartment.

PMID- 9657111
TI  - Antiviral activity and toxicity of fialuridine in the woodchuck model of
      hepatitis B virus infection.
AB  - Woodchucks were used to study the antiviral activity and toxicity of fialuridine
      (FIAU; 1,-2'deoxy-2'fluoro-1-beta-D-arabinofuranosyl-5-iodo-uracil). In an
      initial experiment, groups of six chronic woodchuck hepatitis virus (WHV) carrier
      woodchucks received daily doses of FIAU by intraperitoneal injection for 4 weeks.
      At 0.3 mg/kg/d, the antiviral effect was equivocal, but at 1.5 mg/kg/d, FIAU had
      significant antiviral activity. No evidence of drug toxicity was observed during
      the 4-week period of treatment or during posttreatment follow-up. In a second
      experiment, groups of nine WHV carriers or uninfected woodchucks were given 1.5
      mg/kg/d of FIAU orally for 12 weeks, and the results compared with placebo
      treated controls. After 4 weeks, the serum WHV-DNA concentration in the FIAU
      treated carrier group was two to three logs lower than that in the placebo
      treated group. After 12 weeks of FIAU treatment, serum WHV DNA was not detectable
      by conventional dot-blot analysis, hepatic WHV-DNA replicative intermediates (RI)
      had decreased 100-fold, and hepatic expression of WHV core antigen was remarkably
      decreased. No evidence of toxicity was observed after 4 weeks, but, after 6 to 7
      weeks, food intake decreased and, after 8 weeks, the mean body weights of
      woodchucks treated with FIAU were significantly lower than controls. Anorexia,
      weight loss, muscle wasting, and lethargy became progressively severe, and all
      FIAU-treated woodchucks died or were euthanized 78 to 111 days after treatment
      began. Hepatic insufficiency (hyperbilirubinemia, decreased serum fibrinogen,
      elevated prothrombin time), lactic acidosis, and hepatic steatosis were
      characteristic findings in the final stages of FIAU toxicity in woodchucks. The
      syndrome of delayed toxicity in woodchucks was similar to that observed
      previously in humans treated with FIAU, suggesting that the woodchuck should be
      valuable in future investigations of the molecular mechanisms of FIAU toxicity in
      vivo and for preclinical toxicological evaluation of other nucleoside analogs
      before use in patients.

PMID- 9657112
TI  - Continuous human cell lines inducibly expressing hepatitis C virus structural and
      nonstructural proteins.
AB  - Investigation of the hepatitis C virus (HCV) life cycle and the evaluation of
      novel antiviral strategies are limited by the lack of an efficient cell culture
      system. Therefore, continuous human cell lines inducibly expressing the entire
      HCV open reading frame were generated with use of a tetracycline-regulated gene
      expression system. HCV transgenes were found to be chromosomally integrated in a
      head-to-tail configuration. Northern blot analyses revealed a tightly regulated
      unspliced transcript of approximately 9 kilobases (kb). HCV structural and
      nonstructural proteins were faithfully processed, indicating that the cellular
      and viral proteolytic machineries and posttranslational modification pathways are
      fully functional in these cell lines. Steady state expression levels could be
      regulated over a broad range by the concentration of tetracycline present in the
      culture medium. Kinetic analyses revealed a half-life of less than 1 hour for the
      HCV RNA whereas a half-life of approximately 9.5, 12, 11, and 10 hours was found
      for core, NS3, NS4A, and NS5A proteins, respectively. Viral proteins were found
      to colocalize in the cytoplasm in a pattern characteristic of the endoplasmic
      reticulum. High-level expression of HCV proteins in the fully induced state was
      toxic to the cells. These cell lines provide a unique in vitro system to analyze
      structural and functional properties of HCV proteins, their interactions with
      cellular proteins and pathways, and the requirements for HCV morphogenesis. In
      addition, they should prove useful for the evaluation of novel antiviral
      strategies against hepatitis C in a well-defined and reproducible cellular
      context.

PMID- 9657113
TI  - Cytokine and hepatitis B virus DNA co-immunizations enhance cellular and humoral
      immune responses to the middle but not to the large hepatitis B virus surface
      antigen in mice.
AB  - Genetic immunization is a potentially useful strategy to prevent or treat
      hepatitis B virus (HBV) infection. We have previously shown that HBV envelope
      proteins are highly immunogenic using this technique. The large envelope protein
      (LHBs), however, induced significantly weaker humoral and cellular immune
      responses when compared with the middle envelope protein (MHBs). We studied the
      effect of co-immunizations with cytokine DNA expression constructs encoding for
      interleukin (IL)-2 and (GM-CSF) on the immunogenicity of LHBs at the B-and T-cell
      level. Co-immunizations of mice with plasmids encoding for MHBs and IL-2 or GM
      CSF increased anti-HBs responses, helper T-cell proliferative activity, and
      cytotoxic T lymphocyte (CTL) killing. In contrast, co-immunizations of plasmids
      encoding for LHBs and IL-2 or GM-CSF had no effect on humoral and cellular immune
      responses. LHBs did not inhibit the production or secretion of IL-2 and GM-CSF.
      In addition, IL-2, tumor necrosis factor alfa (TNF-alpha), and interferon gamma
      (IFN-gamma) had no suppressive effect on HBV envelope protein expression in
      vitro. Based on these data, MHBs, but not LHBs, genetic immunization can be
      augmented by IL-2 or GM-CSF cytokines.

PMID- 9657114
TI  - Hepatitis C virus persistence in human hematopoietic cells injected into SCID
      mice.
AB  - The issue of infection of peripheral blood mononuclear cells (PBMC) by the
      hepatitis C virus (HCV) has potentially important implications, but is still
      debated. We have used the severe combined immunodeficiency (SCID) mouse model to
      test for the persistence of HCV in PBMC. Hematopoietic cells isolated from 14
      subjects infected by HCV were inoculated intraperitoneally into SCID mice. Serum
      and blood cell samples from these mice were obtained with a mean follow-up of 8
      weeks. As controls, human fibroblasts and sheep PBMC, preincubated with a human
      HCV-positive serum, were inoculated concomitantly into mice and analyzed. HCV-RNA
      positive strands were detected in 7 of 26 serum samples and 8 of 26 cell
      fractions from SCID mice inoculated with HCV-positive PBMC, after 8 weeks of
      follow-up. In contrast, no HCV RNA was detectable in the 10 control mice. HCV-RNA
      negative strands were detected in only 2 of 10 tested samples from 2 mice, and
      both positive mice had been inoculated with PBMC from HCV-positive subjects with
      malignant hematopoietic syndrome. Our study offers strong evidence for the
      persistence of HCV infection in mononuclear cells. Our results are also
      consistent with a low rate of HCV multiplication. This SCID mouse model might
      therefore be useful in analyzing the mechanisms of HCV persistence in mononuclear
      cells.

PMID- 9657115
TI  - Human and murine antibody recognition is focused on the ATPase/helicase, but not
      the protease domain of the hepatitis C virus nonstructural 3 protein.
AB  - The hepatitis C virus (HCV) nonstructural (NS) 3 protein has been shown to
      possess at least two enzymatic domains. The amino terminal third contains a
      serine-protease domain, whereas the carboxy terminal two thirds is comprised of
      an adenosine triphosphatase (ATPase)/helicase domain. These domains are essential
      for the maturation of the carboxy-terminal portion of the HCV polyprotein and
      catalyze the cap synthesis of the RNA genome. In this report, human and murine
      antibody responses induced by NS3 were characterized using a recombinant full
      length NS3 (NS3-FL) protein, or the isolated protease or ATPase/ helicase
      domains, expressed and purified from Escherichia coli. Sera from 40 patients with
      chronic HCV infection were assayed in enzyme-linked immunoassays (EIAs) for
      antibody binding to the panel of NS3 proteins. Virtually all patient sera
      contained antibodies specific for NS3-FL and the ATPase/helicase domain, whereas
      only 10% of sera reacted with the protease domain of NS3. Human antibodies
      reactive with NS3-FL were highly restricted to the immunoglobulin G1 (IgG1)
      isotype and were inhibited by soluble ATPase/helicase, but not by the protease
      domain. The anti-NS3 (ATPase/helicase) reactivity decreased on denaturation by
      sodium dodecyl sulfate (SDS) and beta-mercaptoethanol (2ME), suggesting the
      recognition of nonlinear or conformational B-cell determinants. Similar to
      infected humans, mice immunized with NS3-FL developed high-titered primary
      antibody responses to the NS3 ATPase/ helicase domain, whereas an anti-NS3
      protease response was not observed after primary or secondary immunizations.
      Thus, the human and murine humoral immune responses to the HCV NS3 protein are
      focused on the ATPase/helicase domain, are restricted to the IgG1 isotype in
      humans, and are conformationally dependent. Unexpectedly, in both species, the
      NS3 protease domain, present in the context of the full-length NS3, appears to
      possess low intrinsic immunogenicity in terms of antibody production.

PMID- 9657116
TI  - Intrahepatic hepatitis C virus-specific cytotoxic T lymphocyte activity and
      response to interferon alfa therapy in chronic hepatitis C.
AB  - Hepatitis C virus (HCV)-specific cytotoxic T lymphocytes (CTL) have been shown to
      play a role in host defense and pathogenesis of chronic HCV infection. Our aim
      was to test the hypothesis that intrahepatic HCV-specific CTL activity may impact
      subsequent response to interferon alfa (IFN-alpha) therapy. Of the 37 patients
      that we have prospectively evaluated for HCV-specific CTL activity in liver, 21
      received IFN therapy, and 19 completed a 6-month course and attended 6 to 18
      months of follow-up. Intrahepatic CD8+ cells were isolated from liver biopsy
      tissue and tested against target cells expressing HCV antigens to determine
      intrahepatic CTL activity. The relationship between treatment response and HCV
      specific CTL activity and other factors known to associate with response
      (genotype, viremia, histology) was analyzed. HCV-specific CTL activity was
      detected in 9 of 21 patients (and 9 of 19 who completed therapy). After 6 months
      of IFN therapy, 8 of 19 (42%) patients had normal serum alanine transaminase
      (ALT) (complete responders). After 18 months of follow-up, only 3 patients (16%)
      had a sustained biochemical response. Of the 9 patients with detectable HCV
      specific CTL activity in their liver before treatment, 7 (78%) developed a
      complete response. In contrast, only 1 of the 10 patients with no detectable HCV
      specific CTL activity developed a complete response to IFN (P < .01). In 6 of 8
      patients with a complete response, including the 3 sustained responders, the CTL
      response appeared to be directed predominately to the HCV core region. These data
      suggest that the host immune response, particularly that mediated by CD8+ CTL,
      may be important in determining the outcome of IFN therapy for chronic HCV
      infection. Further understanding of the mechanism of action of IFN should impact
      the design of better therapeutic strategies against chronic HCV infection.

PMID- 9657117
TI  - Sero-clearance of hepatitis B surface antigen in chronic carriers does not
      necessarily imply a good prognosis.
AB  - The incidence of delayed hepatitis B surface antigen (HBsAg) clearance in the
      natural history of chronic hepatitis B virus (HBV)-infected patients was low.
      Previous studies regarding the prognosis in such patients were controversial.
      Among 1,355 chronic carriers from 1985 to 1997, spontaneous HBsAg clearance was
      observed in 55 patients. During a mean follow-up period of 23 months, 18 (32.7%;
      all were male subjects) developed serious complications, including 11 with
      hepatocellular carcinoma (HCC) (9 of them underwent surgical resection), 6 with
      cirrhosis, and 1 with subfulminant liver failure. The overall cumulative
      probability of complications was 29.8% at 4 years, and it was higher in males (P
      = .044) and patients aged 45 years or more (P = .006); the latter carried an 8.6
      fold increased risk (95% CI: 1.2-64.6; P = .037) of adverse events. Histories of
      acute or chronic infection by hepatitis A virus, C virus (HCV), or D virus (HDV)
      were present in 42% of patients. Patients seropositive for antibodies against HCV
      (anti-HCV) or HDV (anti-HDV) had higher alanine transaminase (ALT) levels (>40
      U/L; P = .008) after sero-clearance. HBV DNA was detectable in 31% of 51
      subjects, in 20% of 20 with antibodies against HBsAg, in 40% of 20 with anti-HCV
      or anti-HDV, and also in an HCC patient's serum and tumor. Staining of liver
      HBsAg was positive in 30% of 10 HCC patients. In conclusion, our results
      demonstrated that hepatitis B viremia may persist, and adverse complications were
      not rare in HBsAg-clearance patients. All such patients should be closely
      monitored, which may allow for earlier detection of HCC.

PMID- 9657118
TI  - Modulation of immune responses to hepatitis C virus envelope E2 protein following
      injection of plasmid DNA using single or combined delivery routes.
AB  - Different delivery routes of plasmid DNA may result in the induction of
      differential humoral and cellular immunity. We have studied the influence of two
      main routes of plasmid injection, performed intramuscularly and intraepidermally
      using a gene gun, for the induction of immune responses specific to hepatitis C
      virus (HCV) envelope protein E2. Three plasmids expressing different immunogenic
      domains of E2 (amino acids [aa] 384443, aa 504-555, and aa 384-746) were injected
      into BALB/c mice according to five different protocols using various combinations
      of intramuscular (i.m.) or intraepidermal (i.e.) primary and booster injections.
      Seroconversion rates, antibody titers and isotypes, epitope recognition, and T
      helper (Th) release cytokine profiles were analyzed. Antibody titers and epitope
      recognition were linked to either or both the nature of the immunogen expressed
      and the delivery route chosen. In all cases, the lowest antibody titers were
      obtained using single i.m.-based protocols. Independently of the antibody titers
      generated, only some specific i.e.-combined delivery routes induced antibodies
      able to recognize determinants located in the N-terminal of E2 (aa 384411 and aa
      411437) and mimicked by synthetic peptides. By contrast, the antibody isotypes
      and the splenic cytokine production identified were independent of the plasmids
      used and the delivery route implemented. All conditions resulted in Th-1 like
      responses suggested by the exclusive detection of IgG2a and 2b antibodies and the
      production of interferon gamma (INF-gamma) but no interleukin-4 (IL-4). Overall,
      our results suggest that the combination of i.m. and i.e. delivery routes
      provides the most efficient way to induce a broad immune response against HCV-E2.

PMID- 9657119
TI  - Hepatitis C virus dynamics in vivo: effect of ribavirin and interferon alfa on
      viral turnover.
AB  - Treatment of patients with chronic hepatitis C with recombinant interferon alfa
      (rIFN-alpha) can cause a decrease of serum transaminases and hepatitis C virus
      (HCV) RNA. Recent trials evaluating combination therapy of IFN-alpha and
      ribavirin suggested a potential synergistic effect. From serial measurements of
      serum HCV RNA concentrations following treatment-induced perturbation of the
      balance between virus production and clearance, we compared the antiviral
      efficacy of both IFN-alpha alone and IFN-alpha in combination with ribavirin.
      Chronically HCV-infected patients were treated with either 3 x 3 MU or 3 x 6 MU
      rIFN-alpha per week or 3 x 6 MU rIFN-alpha plus 14 mg/kg of body weight ribavirin
      per day. The time-dependent HCV RNA concentrations during antiviral treatment
      were analyzed by iterative least-squares regression. After initiation of
      antiviral therapy, HCV RNA declined exponentially below the detection limit of
      the reverse-transcription polymerase chain reaction assay (1,000 HCV RNA
      molecules per milliliter) in 10 of 26 (39%), 10 of 19 (53%), and 10 of 18
      patients (56%) treated with 3 x 3 MU, 3 x 6 MU rIFN-alpha without and with
      ribavirin, respectively. Viral clearance from serum was faster in patients
      treated with 3 x 6 MU rIFN-alpha (t1/2 = 0.23 +/- 0.15) compared with patients
      treated with 3 x 3 MU rIFN-alpha per week (0.67 +/- 0.36 days) (P < .004).
      However, half-lives of viral clearance were similar in patients treated with rIFN
      alpha or rIFN-alpha plus ribavirin. For virus release from infected hepatocytes,
      absence and presence of ribavirin yielded half-lives of t1/2 = 2.54 +/- 2.10 and
      t1/2 = 1.99 +/- 1.70, respectively, indicating that ribavirin does not
      significantly inhibit HCV production. In conclusion, the data of the present
      study indicate that higher rIFN-alpha doses accelerate viral clearance from
      serum. Ribavirin (14 mg/kg/d), however, lacks synergistic antiviral effects in
      the treatment of chronic hepatitis C with 3 x 6 MU rIFN-alpha per week.

PMID- 9657120
TI  - Clinicopathology conferences: inflammation-induced cholestasis.

PMID- 9657121
TI  - Does the hepatitis C virus replicate in cells of the hematopoietic lineage?

PMID- 9657122
TI  - Chronic carriers of hepatitis B virus who clear hepatitis B surface antigen: are
      they really "off the hook"?

PMID- 9657123
TI  - Mouse genetics at work: a new model of chronic hepadnavirus infection.

PMID- 9657124
TI  - Without victory there is no survival: transarterial lipiodol chemoembolization
      and hepatocellular carcinoma.

PMID- 9657125
TI  - Hepatitis B virus vaccines: some cryptic issues.

PMID- 9657126
TI  - Detection of hepatocellular carcinoma in cirrhotic livers with lipiodol-CT.

PMID- 9657127
TI  - Chronic leukemias.

PMID- 9657128
TI  - The real CD34+ events: simplicity or complexity?

PMID- 9657129
TI  - Expansion of the nonadherent myeloid cell population by monoclonal antibodies
      against tenascin-C in murine long-term bone marrow cultures.
AB  - Tenascin-C, a predominantly mesenchymal extracellular matrix protein, has a
      restricted distribution in adult tissues. It has previously been shown that this
      protein is expressed in the bone marrow. In this paper we show that murine
      myeloid and lymphoid long-term bone marrow cultures differ in their expression of
      tenascin-C splice variants. In the adherent stromal layer of myeloid cultures,
      the 260-kDa polypeptide encoded by the 8-kb mRNA was the major splice variant,
      whereas in the stromal layer of lymphoid cultures both the shorter 210-kDa
      polypeptide encoded by the 6-kb mRNA and the 260-kDa polypeptide were abundantly
      expressed. However, in both culture systems the larger 260-kDa tenascin-C
      polypeptide was the major isoform secreted in the culture supernatant. This
      finding is in agreement with previous reports indicating that the smaller 210-kDa
      isoform is preferentially deposited in the stroma, whereas the alternatively
      spliced segment in the 260-kDa tenascin-C may contain anti-adhesive domains.
      Glucocorticoids in myeloid long-term bone marrow cultures and in the MC3T3-G2/PA6
      cell line downregulated the expression of tenascin-C. In the present study we
      observed that this was due primarily to downregulation of the 8-kb major splice
      variant of the tenascin-C mRNA. We also studied the possible role of tenascin-C
      in the bone marrow by using antibodies against tenascin-C in long-term bone
      marrow cultures. We found that three monoclonal antibodies against the
      carboxyterminal type III fibronectin repeats of tenascin-C (TNCfn 7-8) increased
      the number of the non-adherent myeloid cells in myeloid long-term bone marrow
      cultures. It has recently been suggested that the TNCfn 6-8 domain of tenascin-C
      binds to the alpha8beta1 integrin. Using Northern blotting, we found that the
      integrin alpha8 subunit was expressed in adherent cells in bone marrow cultures,
      raising the possibility that tenascin-C acts in bone marrow cultures by binding
      to the alpha8beta1 integrin.

PMID- 9657130
TI  - Assessment of proliferative and colony-forming capacity after successive in vitro
      divisions of single human CD34+ cells initially isolated in G0.
AB  - Exit of primitive hematopoietic progenitor cells (HPCs) from the G0 phase of the
      cell cycle in response to in vitro cytokine stimulation is a limiting step in
      successful ex vivo expansion. Simultaneous DNA/RNA staining with Hoechst 33342
      and pyronin Y was used to separate human bone marrow CD34+ cells residing in G0
      (G0CD34+) from those cycling in G1 and S/G2+M. Compared with CD34+ cells isolated
      in G1, G0CD34+ cells were characterized by a delayed response to cytokine
      stimulation and were enriched for long-term hematopoietic culture-initiating
      cells. We next compared the activation kinetics of individually sorted G0CD34+
      cells stimulated with stem cell factor (SCF), flt3-ligand (FL), or interleukin-3
      (IL-3) as single factors. In a novel clonal proliferation assay, the functional
      status of cells that had remained quiescent after an initial 7-day period and of
      those that had completed successive division cycles under each of these three
      factors was evaluated by assessment of subsequent proliferative capacity and
      maintenance of colony-forming cell precursor (pre-CFC) activity. All three
      cytokines were equally able to support the survival of primitive HPCs in the
      absence of cell division. Cells that did not respond to any cytokine stimulation
      for 7 days retained higher proliferative and pre-CFC activities than dividing
      cells. The hematopoietic function of cells that divided in response to SCF, FL,
      or IL-3 decreased after each division cycle. However, G0CD34+ cells displayed a
      heterogeneous response pattern to cytokine stimulation whereby SCF appeared to
      have a superior ability to promote the cycling of cells with high proliferative
      and pre-CFC activities. These results indicate that HPCs reside in opposing
      hierarchies of hematopoietic potential and responsiveness to cytokine
      stimulation. The data also begin to indicate relationships between cellular
      division in response to different stimuli and maintenance of hematopoietic
      function.

PMID- 9657131
TI  - Effect of interleukin-12 on antitumor activity of human umbilical cord blood and
      bone marrow cytotoxic cells.
AB  - Interleukin (IL)-12, a natural killer (NK) cell stimulatory factor, is a
      heterodimeric cytokine that is known to be a potent activator of non-major
      histocompatibility complex-restricted cytotoxicity by peripheral blood-derived NK
      cells. NK cells (CD3-CD16+/CD56+) represent approximately 15% of human umbilical
      cord blood mononuclear cells (HUCB MNCs) and are known to be highly sensitive to
      activation by IL-2. In the present study, we monitored the effect of IL-12 on the
      cytotoxic activity, proliferation, and phenotypic expression of HUCB-derived
      resting and IL-2-activated cytotoxic cells and compared these parameters with
      those of bone marrow (BM)-derived cells. Lymphocytes were separated from HUCB by
      3% gelatin sedimentation and incubated with IL-12 and/or IL-2 for 18 hours. At
      effector:target ratios of 40:1 and 20:1, IL-12 (50 U/mL) significantly increased
      both resting and IL-2-activated NK cell-mediated cytotoxicity in a standard 51Cr
      release assay against both NK-sensitive (K562) and NK-resistant (Colo-205) cell
      lines. In addition, resting and IL-2-activated cytotoxic cells derived from HUCB
      exhibited superior cytolytic ability compared with BM-derived cells. This
      increase was observed in resting cells as well as in those that were preincubated
      with IL-12. Moreover, HUCB-derived cells were found to be more sensitive to IL-12
      activation than cytotoxic cells from BM. To evaluate the involvement of accessory
      cells, NK cells were purified from HUCB using immunomagnetic beads, and these
      cells were found to have a lower response to treatment with IL-12 than unpurified
      populations. HUCB MNCs exhibited a nonsignificant increase in proliferation after
      IL-12 treatment and were better able to respond to IL-12 activation than BM MNCs.
      Following an 18-hour incubation, IL-12 was able to cause upregulation of CD25 and
      CD69 activation antigens, whereas no significant change in expression of CD16 and
      CD56 NK cell surface antigens, CD3 on T cells, or IL-12 receptor was observed.
      Similarly, IL-12 did not affect NK cell:target cell conjugation as assessed by
      fluorescence-activated cell sorting. Our results indicate that HUCB-derived NK
      mediated cytotoxic capabilities can be increased by IL-12, a finding that may
      have clinical relevance.

PMID- 9657132
TI  - Enhanced lymphoid cell recovery after bone marrow transplantation: correlation
      with the presence of costimulatory antibodies in serum.
AB  - We describe a patient with T cell deficiency who underwent bone marrow
      transplantation (BMT) from an HLA-identical brother. The patient's white blood
      cell count recovered with exceptional rapidity post-BMT: after 7 to 9 days it
      rose sharply to 98x10(9) cells/L, 76% of which were mononuclear leukocytes. It
      then decreased, and a second peak was observed 250 days post-BMT. Lymphocytes
      from both peaks displayed a phenotype of mature T cells together with
      characteristics of a constitutively activated state; that is, they 1) exhibited
      high levels of tyrosine-phosphorylated T cell receptor (TCR) zeta chain, 2)
      spontaneously secreted IL-2, 3) expressed activation specific cell surface
      markers, and 4) were unresponsive to in vitro stimuli. The increased cell counts
      in both peaks correlated with the presence of anti-lymphocytic antibodies in the
      patient's serum, which reacted with peripheral blood lymphocytes (PBLs) both from
      the donor and from unrelated individuals. These antibodies were present before
      BMT and reappeared post-BMT. Variable number tandem repeats analysis revealed
      that the patient's PBLs were chimeras for up to 2 years post-BMT. This finding
      could explain the newly synthesized post-BMT anti-lymphocytic antibodies and the
      appearance of the second WBC peak during that period. The patient's anti
      lymphocytic antibodies displayed costimulatory activity, enhancing the in vitro
      proliferation of normal T cells suboptimally activated via the TCR. The unique
      characteristics of these antibodies could explain the enhanced T cell recovery
      observed post-BMT as well as the constitutive activation state of these cells.
      Furthermore, such antibodies may eventually facilitate development of a
      therapeutic method for inducing enhanced post-BMT recovery.

PMID- 9657133
TI  - Characterization of CD34+ thymic stromal cells located in the subcapsular cortex
      of the human thymus.
AB  - In this paper we report that suspensions of human fetal thymocytes contain cells
      that express high levels of CD34 and Thy-1. These cells were characterized with
      regard to location within the thymus, phenotype, and function. Confocal laser
      scan analysis of frozen sections of fetal thymus with anti-CD34 and Thy-1
      antibodies revealed that the double-labeled cells were located in the
      pericortical area. In addition, it was found that the CD34+Thy-1+ cells lacked
      CD45 and CD50, indicating that these cells are not of hematopoietic origin; this
      was confirmed by the finding that these cells could be cultured as adherent cells
      in a medium with cholera toxin and dexamethasone, but failed to grow in mixtures
      of hematopoietic growth factors. Further analysis indicated that most cultured
      CD34+Thy-1+ cells expressed cytokeratin (CK) 14 but lacked CK 13, suggesting that
      these cells are immature epithelial cells. Cultured CD34+Thy-1+ cells were able
      to induce differentiation of CD1-CD34+CD3-CD4-CD8- thymic precursors into
      CD4+CD8+ cells in a reaggregate culture in the absence of exogenous cytokines.
      The CD4+CD8+ cells that developed in these cultures did not express CD3,
      indicating that CD34+Thy-1+ thymic stromal cells are not capable of completing
      full T cell differentiation of thymic hematopoietic progenitor cells.

PMID- 9657134
TI  - The bone marrow stromal environment is a major factor in myeloma cell resistance
      to dexamethasone.
AB  - Dexamethasone (Dex), which is often used for the treatment of multiple myeloma,
      produces rapid reductions in tumor mass and improvement in disease symptoms;
      however, it is not curative, and drug-resistant cells eventually emerge. To
      elucidate this apparent paradox, we tested the effect of the bone marrow
      environment on myeloma cell response to this drug. To determine whether bone
      marrow stroma provides sufficient amounts of interleukin (IL)-6 to protect
      myeloma cells against the effects of Dex, we compared the production of IL-6 by
      marrow stromal cells from four myeloma patients before, during, and after
      exposure to 10(-7) M Dex, and found that even in the presence of this drug,
      stromal cells continued to produce IL-6, albeit in reduced concentrations. We
      tested the ability of stromal cells to protect myeloma cells, purified from the
      bone marrow of seven patients by cell sorting on the basis of CD38 and CD45
      expression, and two light-scatter parameters, from Dex-induced apoptosis. In
      contrast to mature CD38+CD45- cells, which were not protected, coculture with
      stroma very effectively protected immature CD38+CD45+ myeloma cells from Dex.
      These data may explain the palliative efficacy of Dex treatment and provide a
      rationale for combining IL-6 antagonists with Dex to overcome the IL-6-mediated
      resistance of immature tumor cells.

PMID- 9657135
TI  - Addition of a bone marrow "facilitating cell" population increases stem cell
      derived cobblestone area formation in impaired long-term bone marrow culture
      stroma.
AB  - Treatment of mouse bone marrow (BM) with rabbit anti-mouse brain serum (RAMBS)
      plus complement (C') depletes several cell types, including T cells and
      facilitating cells (FCs), that is, cells that facilitate engraftment of sorted
      allogeneic stem cells (SCs) in vivo. In the present study, treatment of BM with
      RAMBS+C' resulted in the depletion of approximately half of the late cobblestone
      area (CA)-forming stem cells as assayed on irradiated long-term bone marrow
      culture (LTBMC) stroma. In addition, LTBMC of RAMBS+C'-treated BM produced
      functionally impaired stroma with reduced ability to support CA formation by
      nontreated exogenous SCs. This stromal impairment was not due to depletion of
      TCRalphabeta T cells in the BM, because BM cultures from TCR alpha-chain knockout
      mice supported normal numbers of exogenous CAs. Because CD8+/TCR- cells are
      enriched for FCs, we tested the effect of adding these cells back to the treated
      BM prior to culture. The sorted FCs alone did not produce CAs, but did improve
      the ability of the impaired stroma to support late CA formation by sorted SCs.
      These studies provide a new model for dissecting the roles of different cellular
      components of BM in producing functional stroma that supports CA formation by
      SCs, and show that the number of CAs formed depends on the "quality" of the
      stroma as well as the number of SCs seeded. These findings further suggest that
      CD8+/TCR- BM cells may be important for the establishment of functional stroma.

PMID- 9657136
TI  - The murine stromal cell line AFT024 acts specifically on human CD34+CD38-
      progenitors to maintain primitive function and immunophenotype in vitro.
AB  - A stromal cell line derived from murine fetal liver (AFT024) has been
      demonstrated to maintain long-term repopulating murine stem cells for up to 7
      weeks in vitro. We evaluated the ability of AFT024 to maintain the
      immunophenotype and function of primitive human progenitors in vitro by comparing
      the cocultivation of CD34+CD38 cells on AFT024 with that on primary human stroma
      (HS). We have previously reported that within the CD34+CD38- population of bone
      marrow and cord blood, a highly primitive progenitor subpopulation can be
      identified functionally by its ability to generate colony forming unit-cells (CFU
      Cs) in extended long-term culture (ELTC), that is, beyond 60 days of stromal
      cocultivation. Cocultivation of bone marrow and cord blood CD34+CD38-cells on
      AFT024 produced significantly greater cell expansion (p=0.0002) and CFU-C output
      (p=0.0007) during the ELTC period compared with culturing on HS. CFU-C production
      continued up to 9 weeks longer on AFT024 stroma. After 3 to 4 weeks of bulk
      culture on either AFT024 or HS, cells were replated in a limiting dilution to
      measure the number of cobblestone area-forming cells (CAFCs) maintained on each
      stroma. AFT024 maintained significantly more CAFCs than did HS (n=3, p=0.002).
      Fluorescence-activated cell sorter analysis of AFT024 and HS cocultures showed
      that both the frequency (p=0.018) and absolute number (p=0.027) of CD34+CD38-
      cells were significantly higher in cultures on AFT024 than in those on HS (n=9).
      The effects of AFT024 on preservation of primitive progenitors were not seen in
      transwell (noncontact) cultures. Thus, AFT024 acts by direct contact to maintain
      the phenotype and function of the most primitive and quiescent human progenitors
      currently identifiable by in vitro assays.

PMID- 9657137
TI  - Role of plasma and platelet von Willebrand factor in arterial thrombogenesis and
      hemostasis in the pig.
AB  - To evaluate the relative role of plasma and platelet von Willebrand factor (vWF)
      pools in hemostasis and arterial thrombogenesis, pigs with vW disease (vWD) were
      injected with vWF concentrate and/or grafted with bone marrow from a normal pig.
      Hemostasis was assessed by measurement of ear immersion bleeding time, factor
      VIII (FVIII) activity, and plasma and platelet vWF antigen levels. The thrombotic
      process was explored at 650 s(-1) and 1600 s(-1) in an ex vivo cylindrical
      perfusion chamber. Pigs with vWD exhibited a prolonged bleeding time (>30
      minutes) compared with normal pigs (<5 minutes); in addition, they showed normal
      platelet adhesion and thrombus formation at 650 s(-1) but profoundly reduced
      platelet adhesion and thrombus formation at 1600 s(-1). Each experiment was
      performed before and 3 and 24 hours after injection of vWF concentrate. In our
      bleeding time study, only plasma vWF restoration induced a partial but delayed
      correction (24 hours postinjection), which was correlated with the highest
      measured level of FVIII activity. In the perfusion chamber model, restoration of
      plasma or platelet vWF pools resulted in similar partial correction of platelet
      adhesion and average thrombus size. In the perfused pigs, the maximum correction
      occurred 3 hours postinjection. Platelet deposition reached normal values after
      vWF concentrate was injected into a grafted pig. The present results suggest that
      when both plasma and platelet vWF levels are restored in vWD pigs, bleeding time
      and the thrombotic process are normalized according to different kinetics and
      with differing degrees of effectiveness.

PMID- 9657138
TI  - Serial bone marrow sampling for long-term follow up of human hematopoiesis in
      NOD/SCID mice.
AB  - The study of long-term human hematopoiesis in immunodeficient mice is greatly
      facilitated by sequential bone marrow (BM) sampling in individual animals. Until
      now, however, the only way to obtain these samples was by sacrificing the mice.
      In this paper we describe a novel technique for obtaining BM cells by aspiration
      from the femur of living mice. The technique is simple and efficient and does not
      disable the animals. On average 1.6+/-1x10(6) nucleated cells can be collected
      from one femur at a time, which is sufficient for flow cytometry analysis,
      cytospin preparations, and polymerase chain reaction assays. The cellular
      composition of the samples obtained by puncture is identical to that of BM
      harvested by flushing the femur after sacrificing the animals. We present the
      results of 81 punctures of the femur in Hu-NOD/SCID chimeras engrafted with
      Ficoll-separated or CD34bright purified cells from human umbilical cord blood.

PMID- 9657139
TI  - Yeast retrotransposons: finding a nice quiet neighborhood.

PMID- 9657140
TI  - Memory and the brain: what's right and what's left?

PMID- 9657141
TI  - The cadherin superfamily at the synapse: more members, more missions.

PMID- 9657142
TI  - Hair today, gone tomorrow: transgenic mice with human repair deficient hair
      disease.

PMID- 9657143
TI  - Regulation of Drosophila neurogenesis by RNA:RNA duplexes?

PMID- 9657144
TI  - A 9 A resolution X-ray crystallographic map of the large ribosomal subunit.
AB  - The 50S subunit of the ribosome catalyzes the peptidyl-transferase reaction of
      protein synthesis. We have generated X-ray crystallographic electron density maps
      of the large ribosomal subunit from Haloarcula marismortui at various resolutions
      up to 9 A using data from crystals that diffract to 3 A. Positioning a 20 A
      resolution EM image of these particles in the crystal lattice produced phases
      accurate enough to locate the bound heavy atoms in three derivatives using
      difference Fourier maps, thus demonstrating the correctness of the EM model and
      its placement in the unit cell. At 20 A resolution, the X-ray map is similar to
      the EM map; however, at 9 A it reveals long, continuous, but branched features
      whose shape, diameter, and right-handed twist are consistent with segments of
      double-helical RNA that crisscross the subunit.

PMID- 9657145
TI  - F1-ATPase is a highly efficient molecular motor that rotates with discrete 120
      degree steps.
AB  - A single molecule of F1-ATPase, a portion of ATP synthase, is by itself a rotary
      motor in which a central gamma subunit rotates against a surrounding cylinder
      made of alpha3beta3 subunits. Driven by three catalytic betas, each fueled with
      ATP, gamma makes discrete 120 degree steps, occasionally stepping backward. The
      work done in each step is constant over a broad range of imposed load and is
      close to the free energy of hydrolysis of one ATP molecule.

PMID- 9657146
TI  - LMA1 binds to vacuoles at Sec18p (NSF), transfers upon ATP hydrolysis to a t
      SNARE (Vam3p) complex, and is released during fusion.
AB  - Vacuole fusion requires Sec18p (NSF), Sec17p (alpha-SNAP), Ypt7p (GTP binding
      protein), Vam3p (t-SNARE), Nyv1p (v-SNARE), and LMA1 (low Mr activity 1, a
      heterodimer of thioredoxin and I(B)2). LMA1 requires Sec18p for saturable, high
      affinity binding to vacuoles, and Sec18p "priming" ATPase requires both Sec17p
      and LMA1. Either the sec18-1 mutation and deletion of I(B)2, or deletion of both
      I(B)2 and p13 (an I(B)2 homolog) causes a striking synthetic vacuole
      fragmentation phenotype. Upon Sec18p ATP hydrolysis, LMA1 transfers to (and
      stabilizes) a Vam3p complex. LMA1 is released from vacuoles in a phosphatase
      regulated reaction. This LMA1 cycle explains how priming by Sec18p is coupled to
      t-SNARE stabilization and to fusion.

PMID- 9657147
TI  - Developmental regulation of invariant chain proteolysis controls MHC class II
      trafficking in mouse dendritic cells.
AB  - Dendritic cells (DCs) developmentally regulate their capacity for antigen
      presentation by controlling the transport and surface expression of MHC class II
      molecules. These events reflect a developmental regulation of invariant (Ii)
      chain cleavage, most likely by the cysteine protease cathepsin S. In immature
      DCs, inefficient Ii chain cleavage due to low cathepsin S activity leads to the
      transport of class II-Ii chain complexes to lysosomes, while in mature DCs,
      elevated cathepsin S activity results in efficient delivery of class II alphabeta
      dimers to the plasma membrane. Cathepsin S is not controlled transcriptionally
      but by a novel mechanism involving alterations in the expression and localization
      of an endogenous cathepsin S inhibitor cystatin C. Thus, the ratio of cystatin C
      to cathepsin S in developing DCs helps to determine the fate of newly synthesized
      MHC class II molecules.

PMID- 9657148
TI  - Targeted disruption of mouse conventional kinesin heavy chain, kif5B, results in
      abnormal perinuclear clustering of mitochondria.
AB  - Mouse kif5B gene was disrupted by homologous recombination. kif5B-/- mice were
      embryonic lethal with a severe growth retardation at 9.5-11.5 days postcoitum. To
      analyze the significance of this conventional kinesin heavy chain in organelle
      transport, we studied the distribution of major organelles in the extraembryonic
      cells. The null mutant cells impaired lysosomal dispersion, while brefeldin A
      could normally induce the breakdown of their Golgi apparatus. More prominently,
      their mitochondria abnormally clustered in the perinuclear region. This
      mitochondrial phenotype was reversed by an exogenous expression of KIF5B, and a
      subcellular fractionation revealed that KIF5B is associated with mitochondria.
      These data collectively indicate that kinesin is essential for mitochondrial and
      lysosomal dispersion rather than for the Golgi-to-ER traffic in these cells.

PMID- 9657149
TI  - Thrombospondin-1 is a major activator of TGF-beta1 in vivo.
AB  - The activity of TGF-beta1 is regulated primarily extracellularly where the
      secreted latent form must be modified to expose the active molecule. Here we show
      that thrombospondin-1 is responsible for a significant proportion of the
      activation of TGF-beta1 in vivo. Histological abnormalities in young TGF-beta1
      null and thrombospondin-1 null mice were strikingly similar in nine organ
      systems. Lung and pancreas pathologies similar to those observed in TGF-beta1
      null animals could be induced in wild-type pups by systemic treatment with a
      peptide that blocked the activation of TGF-beta1 by thrombospondin-1. Although
      these organs produced little active TGF-beta1 in thrombospondin null mice, when
      pups were treated with a peptide derived from thrombospondin-1 that could
      activate TGF-beta1, active cytokine was detected in situ, and the lung and
      pancreatic abnormalities reverted toward wild type.

PMID- 9657150
TI  - Regulation of armadillo by a Drosophila APC inhibits neuronal apoptosis during
      retinal development.
AB  - We find that inactivation of a Drosophila homolog of the tumor suppressor APC (D
      APC) causes retinal neuronal degeneration and pigment cell hypertrophy, a
      phenotype remarkably similar to that found in humans with germline APC mutations.
      Retinal degeneration in the D-APC mutant results from apoptotic cell death, which
      accompanies a defect in neuronal differentiation. Reduction in the Drosophila
      beta-catenin, Armadillo (Arm), rescues the differentiation defect and prevents
      apoptosis in the D-APC mutant, while Arm overexpression mimics D-APC
      inactivation. A mutation in dTCF, the DNA-binding protein required in Arm
      mediated signal transduction, can eliminate the cell death without rescuing the
      differentiation defect in D-APC mutants. Uncoupling of these two Arm-induced
      processes suggests a novel role for the Arm/dTCF complex in the activation of
      apoptosis.

PMID- 9657151
TI  - Coordination of growth and cell division in the Drosophila wing.
AB  - In most tissues, cell division is coordinated with increases in mass (i.e.,
      growth). To understand this coordination, we altered rates of division in cell
      clones or compartments of the Drosophila wing and measured the effects on growth.
      Constitutive overproduction of the transcriptional regulator dE2F increased
      expression of the S- and M-phase initiators Cyclin E and String (Cdc25), thereby
      accelerating cell proliferation. Loss of dE2F or overproduction of its
      corepressor, RBF, retarded cell proliferation. These manipulations altered cell
      numbers over a 4- to 5-fold range but had little effect on clone or compartment
      sizes. Instead, changes in cell division rates were offset by changes in cell
      size. We infer that dE2F and RBF function specifically in cell cycle control, and
      that cell cycle acceleration is insufficient to stimulate growth. Variations in
      dE2F activity could be used to coordinate cell division with growth.

PMID- 9657152
TI  - Arabidopsis LEAFY COTYLEDON1 is sufficient to induce embryo development in
      vegetative cells.
AB  - The Arabidopsis LEAFY COTYLEDON1 (LEC1) gene is required for the specification of
      cotyledon identity and the completion of embryo maturation. We isolated the LEC1
      gene and showed that it functions at an early developmental stage to maintain
      embryonic cell fate. The LEC1 gene encodes a transcription factor homolog, the
      CCAAT box-binding factor HAP3 subunit. LEC1 RNA accumulates only during seed
      development in embryo cell types and in endosperm tissue. Ectopic postembryonic
      expression of the LEC1 gene in vegetative cells induces the expression of embryo
      specific genes and initiates formation of embryo-like structures. Our results
      suggest that LEC1 is an important regulator of embryo development that activates
      the transcription of genes required for both embryo morphogenesis and cellular
      differentiation.

PMID- 9657153
TI  - Constitutive expression of the CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) gene disrupts
      circadian rhythms and suppresses its own expression.
AB  - The CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) gene encodes a MYB-related transcription
      factor involved in the phytochrome induction of a light-harvesting chlorophyll
      a/b-protein (Lhcb) gene. Expression of the CCA1 gene is transiently induced by
      phytochrome and oscillates with a circadian rhythm. Constitutive expression of
      CCA1 protein in transgenic plants abolished the circadian rhythm of several genes
      with dramatically different phases. These plants also had longer hypocotyls and
      delayed flowering, developmental processes regulated by light and the circadian
      clock. Furthermore, the expression of both endogenous CCA1 and the related LHY
      gene was suppressed. Our results suggest that CCA1 is a part of a feedback loop
      that is closely associated with the circadian clock in Arabidopsis.

PMID- 9657154
TI  - The late elongated hypocotyl mutation of Arabidopsis disrupts circadian rhythms
      and the photoperiodic control of flowering.
AB  - The dominant late elongated hypocotyl (lhy) mutation of Arabidopsis disrupted
      circadian clock regulation of gene expression and leaf movements and caused
      flowering to occur independently of photoperiod. LHY was shown to encode a MYB
      DNA-binding protein. In wild-type plants, the LHY mRNA showed a circadian pattern
      of expression with a peak around dawn but in the mutant was expressed constantly
      at high levels. Increased LHY expression from a transgene caused the endogenous
      gene to be expressed at a constant level, suggesting that LHY was part of a
      feedback circuit that regulated its own expression. Thus, constant expression of
      LHY disrupts several distinct circadian rhythms in Arabidopsis, and LHY may be
      closely associated with the central oscillator of the circadian clock.

PMID- 9657155
TI  - Complementation cloning of NEMO, a component of the IkappaB kinase complex
      essential for NF-kappaB activation.
AB  - We have characterized a flat cellular variant of HTLV-1 Tax-transformed rat
      fibroblasts, 5R, which is unresponsive to all tested NF-kappaB activating
      stimuli, and we report here its genetic complementation. The recovered full
      length cDNA encodes a 48 kDa protein, NEMO (NF-kappaB Essential MOdulator), which
      contains a putative leucine zipper motif. This protein is absent from 5R cells,
      is part of the high molecular weight IkappaB kinase complex, and is required for
      its formation. In vitro, NEMO can homodimerize and directly interacts with IKK-2.
      The NEMO cDNA was also able to complement another NF-kappaB-unresponsive cell
      line, 1.3E2, in which the protein is also absent, allowing us to demonstrate that
      this factor is required not only for Tax but also for LPS, PMA, and IL-1
      stimulation of NF-kappaB activity.

PMID- 9657156
TI  - A critical role for amino-terminal glutamine/asparagine repeats in the formation
      and propagation of a yeast prion.
AB  - The yeast [PSI+] factor propagates by a prion-like mechanism involving self
      replicating Sup35p amyloids. We identified multiple Sup35p mutants that either
      are poorly recruited into, or cause curing of, wildtype amyloids in vivo. In
      vitro, these mutants showed markedly decreased rates of amyloid formation,
      strongly supporting the protein-only prion hypothesis. Kinetic analysis suggests
      that the prion state replicates by accelerating slow conformational changes
      rather than by providing stable nuclei. Strikingly, our mutations map exclusively
      within a short glutamine/asparagine-rich region of Sup35p, and all but one occur
      at polar residues. Even after replacement of this region with polyglutamine,
      Sup35p retains its ability to form amyloids. These and other considerations
      suggest similarities between the prion-like propagation of [PSI+] and
      polyglutamine-mediated pathogenesis of several neurodegenerative diseases.

PMID- 9657157
TI  - Ceruminolytic agents.

PMID- 9657158
TI  - Endogenous lipid (cholesterol) pneumonia associated with bronchogenic carcinoma
      in a cat.
AB  - An 11-year-old, female domestic longhair was presented for dyspnea, vomiting, and
      left forelimb lameness. A mass in the left caudal lung lobe was seen on thoracic
      radiographs. The mass was resected during thoracotomy, and histopathology
      confirmed a diagnosis of endogenous lipid pneumonia. The cat recovered slowly
      from surgery and was euthanized 11 days following discharge because of persistent
      respiratory difficulties. Necropsy findings included lipid pneumonia and
      bronchogenic carcinoma, with probable tumor metastasis to the small intestine,
      spleen, kidney, and left triceps muscle.

PMID- 9657159
TI  - Cutaneous mast cell tumors in cats: 32 cases (1991-1994).
AB  - Case records of 32 cats with cutaneous mast cell tumors (CMCTs) were reviewed.
      Using the Patnaik system for grading canine mast cell tumors, the relationships
      between histopathological grade and patient survival time and tumor recurrence
      were examined. Tumor histopathological grade had no prognostic significance. One
      , two-, and three-year tumor recurrence rates following surgical excision were
      16%, 19%, and 13%, respectively. Incomplete excision was not associated with a
      higher rate of tumor recurrence.

PMID- 9657160
TI  - Gastrointestinal adenocarcinomas metastatic to the testes and associated
      structures in three dogs.
AB  - Primary testicular neoplasms are common in dogs, but metastases to the testes are
      rare. Three dogs had enlargement of the testes and associated structures. Upon
      histological examination, the enlargements were due to metastatic
      adenocarcinomas. Further examination identified the gastrointestinal tract as the
      primary site of the metastatic neoplasms in all three cases. The testicular
      metastases reflected widespread metastatic disease. When metastatic
      adenocarcinoma is found in the testes and associated structures in dogs, the
      gastrointestinal tract should be examined closely for a primary tumor site.

PMID- 9657161
TI  - Infantile desmoid-type fibromatosis in an Akita puppy.
AB  - A 10-week-old Akita puppy was evaluated for a reported umbilical hernia. Repair
      of the hernia had been attempted three times prior to referral. A defect in the
      ventral abdominal wall with an associated soft-tissue mass was identified on
      abdominal radiographs. Exploratory surgery was performed; the mass was resected
      and the abdominal wall defect was repaired. Histopathological evaluation of the
      mass was consistent with infantile desmoid-type fibromatosis.

PMID- 9657162
TI  - Malignant mesenchymoma associated with an unusual vasoinvasive metastasis in a
      dog.
AB  - A case of a malignant mesenchymoma with an unusual, vasoinvasive, metastatic
      behavior in a three-year-old, intact female basset hound is presented. Malignant
      mesenchymomas are rare neoplasms in humans and in dogs. No previous reports of a
      malignant mesenchymoma with vasoinvasive metastasis in the dog were found in the
      literature. The constituent neoplasms are discussed in relation to reports in the
      human and veterinary literature, and a potential etiology for this unique
      presentation is hypothesized.

PMID- 9657163
TI  - Lymphangiosarcoma in a dog presenting with massive head and neck swelling.
AB  - A three-year-old, neutered male Chesapeake Bay retriever was presented for acute
      onset of severe, progressive swelling of the head, neck, and cranial trunk.
      Diffuse lymphangiosarcoma involving the superficial and deep dermis and
      subcutaneous tissue was observed on skin biopsies. Lymphangiosarcoma is a rarely
      reported tumor of the lymphatic system in dogs and cats. The importance of
      obtaining skin biopsies in animals with acute edema of unknown etiology is
      emphasized. Additionally, neoplasia should be considered as a potential diagnosis
      in a dog with an acute onset of edema.

PMID- 9657164
TI  - Spinal epidural empyema in two dogs.
AB  - Extensive, diffuse, epidural spinal cord compression was visualized
      myelographically in two dogs presented for rapid development of nonambulatory
      tetraparesis and paraplegia, respectively. Purulent fluid containing bacterial
      organisms was aspirated percutaneously under fluoroscopic guidance from the
      epidural space of each dog. One dog responded poorly to aggressive medical
      therapy, which included installation of an epidural lavage and drainage system.
      Both dogs were euthanized due to the severe nature of their disorder and the poor
      prognosis. Spinal epidural empyema (i.e., abscess) is a rare condition in humans
      and has not been reported previously in the veterinary literature. Spinal
      epidural empyema should be considered as a differential diagnosis in dogs
      presenting with painful myelopathies, especially when accompanied by fever.

PMID- 9657166
TI  - Uroperitoneum in cats: 26 cases (1986-1995).
AB  - Uroperitoneum (UP) was diagnosed in 26 cats. Trauma was the most common cause
      (84.6%), including blunt abdominal trauma (59.1%), urethral catheterization
      (31.8%), and bladder expression (9.1%). The bladder was the most frequent site of
      urine leakage following blunt abdominal trauma (84.6%), while the urethra was the
      most common site following catheterization (71.4%). Common historical complaints
      were anuria (53.8%) and vomiting (50%). On physical examination, the bladders
      were palpable in nine (69%) of 13 cases; four of the nine had ruptured bladders.
      The ability to urinate did not exclude a diagnosis of UP since four
      noncatheterized cases reportedly urinated. Twenty-five cases were azotemic on
      presentation. The creatinine or potassium (K+) concentration in the serum
      compared to that in the peritoneal effusion (mean ratio, 1:2 and 1:1.9,
      respectively) was a useful indicator for UP. When performed, positive contrast
      radiography was diagnostic. Drainage of urine from the peritoneal cavity appeared
      to improve patient stabilization. Morbidity and mortality depended largely on the
      severity of associated injuries.

PMID- 9657165
TI  - Surgical and chemotherapeutic treatment of alveolar echinococcosis in a dog.
AB  - Surgical removal of macroscopically detectable metacestode tissue followed by
      postoperative chemotherapy according to established human protocols resulted in
      complete clinical remission and immediate normalization of hyperglobulinemia in a
      dog with alveolar echinococcosis (AE). The disease is caused by the metacestode
      stage of the cestode, Echinococcus multilocularis. In endemic areas, AE should be
      included in the differential diagnosis of polycystic liver masses, especially if
      concomitant hyperglobulinemia is present. However, the importance of AE is not
      only the disease of the single dog itself but also the potential risk of
      infection for humans in an endemic area.

PMID- 9657167
TI  - Morbidity and mortality associated with anesthetic management in small animal
      veterinary practice in Ontario.
AB  - During 1993, 66 small animal practices participated in a prospective study to
      evaluate the incidence and details of anesthetic-related morbidity and mortality.
      Considering a total of 8,087 dogs and 8,702 cats undergoing anesthesia, the
      incidences of complications were 2.1% and 1.3%, respectively. Death occurred in
      0.11% and 0.1% of cases, respectively. Logistic regression models were developed
      and showed that a significant odds ratio (OR) of complications in dogs was
      associated with xylazine (OR, 91.5); heart rate monitoring (OR, 3.2); American
      Society of Anesthesiologists (ASA) 3, 4, or 5 classification (OR, 2.5);
      isoflurane (OR, 2.4); butorphanol (OR, 0.35); technician presence (OR, 0.26);
      acepromazine (OR, 0.24); ketamine (OR, 0.21); and mask induction (OR, 0.2).
      Complications in cats were associated with ASA 3, 4, or 5 classification (OR,
      5.3); diazepam (OR, 4.1); intubation (OR, 1.7); butorphanol (OR, 0.45); and
      ketamine (OR, 0.17). Cardiac arrest in dogs was associated with xylazine (OR,
      43.6) and ASA 3, 4, or 5 classification (OR, 7.1). Cardiac arrest in cats was
      associated with ASA 3, 4, or 5 classification (OR, 21.6) and technician presence
      (OR, 0.19). This paper reports the incidences of complications and cardiac arrest
      in small animal practice and identifies common complications and factors that may
      influence anesthetic morbidity and mortality. This information may be useful in
      comparing anesthetic management practices.

PMID- 9657168
TI  - Early detection of canine hip dysplasia: comparison of two palpation and five
      radiographic methods.
AB  - Hip joint laxity was evaluated in four breeds (i.e., greyhound, Labrador
      retriever, Irish setter, hound mixed-breed) of puppies (n=32) by Ortolani's and
      Bardens' maneuvers, by subjective assessment of radiographs (Orthopedic
      Foundation for Animals [OFA] method), and by four radiographic measurement
      indices. Puppies were studied at four, six-to-10, 16-to-18, and 52 weeks of age.
      The purpose of this study was to compare palpation and radiographic methods of
      hip laxity detection in puppies for predicting the development of degenerative
      joint disease (DJD) by one year of age. Twenty-seven (42%) hips developed DJD.
      Ortolani's method was not a reliable predictor of hip dysplasia at six-to-10
      weeks; it was significantly predictive at 16-to-18 weeks but had a high incidence
      of false negatives. Bardens' and subjective (OFA) assessment methods were not
      reliable at six-to-10 or 16-to-18 weeks. Radiographic measurements taken with
      femurs in a neutral position and hips distracted (distraction index [DI] and
      Norberg angle) and measurements taken with femurs extended in OFA position
      (Norberg angle) of six- to 10-week-old puppies accurately predicted DJD
      occurrence by one year of age (p less than 0.01). Distraction index measurement
      (PennHIP method) was the most accurate in predicting the development of DJD (p
      less than 0.001). Distraction index radiography in puppies six-to-10 and 16-to-18
      weeks of age was the most reliable predictor of hip dysplasia. Norberg angle
      measurement was more reliable during hip distraction than when hips were measured
      in the OFA position in 16- to 18-week-old puppies, but had similar reliability in
      six- to 10-week-old puppies.

PMID- 9657169
TI  - The effects of stains and investigators on assessment of morphology of canine
      spermatozoa.
AB  - Percentage and types of morphological abnormalities found in canine spermatozoa
      were evaluated by three investigators using three stains (Giemsa-Wright stain
      [Diff-Quik], eosin Y/nigrosin [Hancock], and eosin B/nigrosin [Society for
      Theriogenology morphology stain] with conventional light microscopy, compared to
      phase contrast microscopy on unstained samples. The percentage of spermatozoa
      with abnormal heads, midpieces, and tails varied by technique and by
      investigator. Average percentages of morphologically normal spermatozoa were
      significantly higher in samples stained with Diff-Quik and samples examined by
      phase contrast microscopy than in samples stained with Hancock or Society for
      Theriogenology morphology stains. No effect of investigator on the percentage of
      morphologically normal spermatozoa was assessed. Results suggest that staining or
      preparation technique may alter the morphology of canine spermatozoa
      artifactually.

PMID- 9657170
TI  - Urinary stress incontinence: surgical treatment.

PMID- 9657171
TI  - A possible link between stress urinary incontinence and detrusor instability in
      the female--urodynamic (pressure/flow) data and speculative considerations.
AB  - The aim of the present investigation was to check voiding mechanics in women with
      stress urinary incontinence (SUI) for differences between patients with stable
      bladders and those with detrusor instability (DI). There were 70 females, 35 with
      stable and 35 with unstable bladders, who had urodynamically proven SUI. All
      underwent medium-fill water cystometry and pressure/flow studies. A relatively
      enhanced detrusor contractility, mirrored by higher values of maximum external
      voiding power and shortening velocity, could be found in the unstable patients.
      Of these, 27 were reassessed urodynamically following surgical cure of the SUI.
      After the operative treatment 17 of the 27 showed stable bladders and a reduced
      detrusor contractility, but no reduced contractility was found in the other 10,
      whose bladders remained unstable. The data reported may suggest that the factor
      responsible for 'idiopathic' DI in SUI patients would also be able to yield
      enhanced bladder mechanical capability. It was tentatively assumed that this
      factor involves an increased urethral sensitivity, possibly secondary to
      incompetence of the urethral closure mechanism, and persisting at times even
      should SUI be surgically relieved.

PMID- 9657172
TI  - Ultrasonographic estimation of postpartum postvoid residual bladder volume: a
      comparison between transabdominal and transvaginal ultrasonography.
AB  - Postvoid residual bladder volume (PVRBV) was estimated in 89 patients with
      postpartum urinary retention using two ultrasonographic volume estimation
      methods. The PVRBV estimated by transabdominal and transvaginal ultrasonography
      are compared using the plot of difference against mean and the paired t-test.
      Neither showed any significant difference between the two methods (paired sample
      t-test, P > 0.05). The two methods have high correlation coefficient of 0.903
      (Spearman's correlation, P < 0.0001). Either ultrasonographic volume estimation
      method gives reasonable bladder volume assessment in postpartum patients and
      could be used interchangeably as the clinical situation requires.

PMID- 9657173
TI  - Transurethral collagen injection for female stress incontinence.
AB  - Periurethral collagen injections have been used to treat female urinary
      incontinence secondary to intrinsic sphincteric deficiency (ISD). As an
      alternative, a transurethral submucosal collagen injection was used in 33
      consecutive women suffering from stress incontinence secondary to ISD at Tulane
      University Medical Center. Prior to the procedure, careful clinical examination
      with a videofluorourodynamic study was performed for each case. The procedure was
      carried out under local anesthesia assisted with monitored anesthesia care (MAC).
      The collagen was injected transurethrally by the long collagen needle (C. R.
      Bard). In the first 11 cases the average cumulative collagen injected per patient
      was 6.1 ml, whereas in the last 22 cases the average was 3.5 ml. As a result of
      the injection 16 patients were dry (48.5%) and 11 were improved (33.3%), with an
      overall success rate of 81.8%. The injection failed in 6 patients (18.1%). The
      mean follow-up was 18.8 months, with a range of 2-33 months. In the successful
      group there was a significant decrease in pretreatment frequency, from an average
      of 8 to 4.9 (P = 0.005) and in nocturia from an average of 2.14 to 0.76 (P =
      0.001). Also, there was a significant decrease in the number of pads, from an
      average of 3.7 to 1.1 (P = 0.001). The stress leak-point pressure showed a
      significant increase, from an average of 68.1 to 93.5 cm H2O (P = 0.03). There
      was no relation between grade of incontinence and the success of the injection.
      Two cases suffered from temporary urinary retention. This study revealed that the
      transurethral submucosal collagen injection is an effective method for treating
      cases of intrinsic sphincteric deficiency. The volume of collagen required to
      produce the seal effect is small and it may decrease the reinjection rate. As
      experience is gained, the procedure time is typically 15 minutes. This makes it a
      reliable, cost-effective and well-controlled method. However, it has a learning
      curve and the cystoscope instruments require minor adaptation for its use.

PMID- 9657174
TI  - Development of generic models for ambulatory vaginal surgery--a preliminary
      report.
AB  - Generic guidelines are applied to reconstructive vaginal operations, so as to
      convert them to ambulatory procedures. Prototype operations are described and
      analyzed. These included conceptualizing vaginal prolapse as a type of
      intussusception caused by vaginal and ligamentous laxity in the middle or
      posterior parts of the vagina; the avoidance of vaginal excision, excessive
      tension, and refashioning excess vaginal tissue from width to length or into a
      partial double-layered repair; the creation of artificial neoligaments; the
      prevention of urinary retention by avoiding tightness in the bladder neck area;
      local anesthetic infiltration; and buttressing vaginal tissue during wound
      healing. A total of 108 patients underwent vaginal surgery on an ambulatory or
      overnight stay basis, 72 under local anesthesia/midazolam. Minimal postoperative
      pain and the absence of catheterization reduced hospital stay from a statewide
      mean of 8 days to 1 day, and return to normal activities from 6 weeks to 7-10
      days. Cure rates (18 months) were: uterovaginal prolapse 22/22, infracoccygeal
      sacropexy 21/23, rectocele 36/38, cystocele/anterior vaginal wall prolapse 21/25.
      Applied as prototypes to reconstructive vaginal surgery, the operations appear to
      be as effective as traditional techniques but far less invasive. They have the
      potential to assist working mothers, the old and infirm, and save the community
      up to $5,500 per patient. It is hoped that the generic models presented may act
      as a basis for the future development of ambulatory vaginal surgical techniques.

PMID- 9657175
TI  - A new concept of the anatomy of the anal sphincter mechanism and the physiology
      of defecation: mass contraction of the pelvic floor muscles.
AB  - We have previously demonstrated both anatomically and physiologically that the
      external anal (EAS) and urethral (EUS) sphincters and the bulbocavernosus muscle
      (BC) originate from the puborectalis muscle (PR). It is hypothesized that
      stimulation of any of these muscles would lead to contraction of all the others.
      Because the levator ani (pubococcygeus) muscle (LA) also has the same innervation
      as the above-mentioned muscles, it is further suggested that it, too, contracts
      reflexly upon stimulation of any of those muscles. The purpose of this study was
      to test this hypothesis. The study comprised 18 healthy volunteers (mean age 36.6
      +/- 8.4 years; 10 men, 8 women). The EAS was stimulated and the response of the
      EUS, PR, LA and BC was determined. Each muscle was thereafter stimulated
      separately and the response of the other pelvic floor muscles registered.
      Stimulation of any of the pelvic floor muscles effected an increased EMG activity
      of the rest of the muscles. The muscle contraction was instantaneous with no
      latency in all the muscles except the LA EMG activity, which showed a mean
      latency of 21.3 +/- 6.6 ms. The pelvic floor muscles' response seems to be
      attributable to muscle stimulation both directly and indirectly through
      activation of pudendal nerve fibers in the muscles. The study demonstrated that
      the pelvic floor muscles behave as one muscle: they contract or relax en masse.
      This 'mass contraction' might explain some of the physiologic phenomena that
      occur during pelvic organ evacuation. However, besides this mass contraction, a
      voluntary 'selective' individual muscle activity exists by which each individual
      muscle acts independently of the others.

PMID- 9657176
TI  - Uroflow in women: an overview and suggestions for the future.
AB  - The literature on uroflowmetry in women is presented and evaluated. Uroflowmeters
      are described and found generally sufficiently accurate, although the errors
      arising from electronic evaluation may invalidate the test. Six flow curve
      patterns are proposed in accordance with described pathological conditions. From
      the literature it is summarized that the normal Qmax is 20-36 ml/s. Qmax is
      linearly correlated to the voided volume, increasing by 5.6 ml/s/100 ml.
      Pregnancy, age and menstrual cycle do not influence Qmax. Several pathological
      conditions have been associated with specific flow curve patterns. These
      conditions are described and associations with the proposed flow definitions
      made.

PMID- 9657177
TI  - Techniques of rectocele repair and their effects on bowel function.
AB  - Gynecologists have traditionally evaluated rectocele repair by its effect on
      vaginal function; coloproctologists have traditionally evaluated its effect on
      bowel function. Hence different operative criteria and surgical techniques have
      arisen, but with very little prospective, objective evaluation. The purpose of
      this review is to describe the surgical techniques used to repair the rectocele
      and the most common investigations used during its evaluation. Anorectal
      investigations identify concomitant pathology, may explain pathophysiology,
      provide objective outcome criteria and attempt to predict the patients that will
      most benefit from surgery. However, because of the complex neuromuscular,
      physiological and mechanical interactions that contribute to impaired rectal
      emptying, their usefulness in improving functional outcome has been limited. Many
      patients experience improvement, but still are left with some symptoms of
      impaired defecation despite anatomic correction.

PMID- 9657178
TI  - The defunctionalized bladder.
AB  - Supravesical urinary diversion without cystectomy is a common procedure performed
      to manage a variety of lower urinary tract pathologies. The purpose of this
      article is to review the complications associated with the bladder left in situ
      and to relate this to the female patient. Complications related to the
      defunctionalized bladder include pyocystis, hemorrhage, pain/spasm and neoplastic
      transformation. The defunctionalized bladder also has implications for sexual
      function, pregnancy and undiversion. The risk factors for complications are
      chronic infection, inadequate drainage, interstitial cystitis and previous
      irradiation. The incidence of neoplastic change in the defunctionalized bladder
      is low, but long-term follow-up is advised, as carcinoma could develop many
      decades after diversion. Sexual function following urinary diversion is better
      preserved when the bladder is retained.

PMID- 9657179
TI  - Preoperative contrast ultrasonographic diagnosis of patent urachal sinus.
AB  - A patent urachal sinus, as well as other congenital urachal anomalies, may be at
      risk of injury during laparoscopy. Leakage of fluid at the midline site of trocar
      entry is the usual postoperative sign of injury to a patent urachal sinus. Pre
      operative diagnosis of this anomaly can prevent injury during laparoscopy. We
      describe a contrast ultrasound technique for diagnosis of patent urachal sinus.

PMID- 9657180
TI  - Total genitourinary reconstruction in adult female epispadias: a report of 2
      cases and literature review.
AB  - Female incontinent episadias is a very rare congenital anomaly presenting in
      childhood. We report 2 cases of adults presenting with this anomaly. These were
      treated by total genitourinary reconstruction in a single stage using a combined
      perineal abdominal approach, with satisfactory results. We recommend this
      technique as the procedure of choice in adults presenting with this rare anomaly.

PMID- 9657181
TI  - Recurrence of stress incontinence after vault suspension: can it be prevented?
AB  - Management of vault prolapse in a patient who has previously undergone successful
      colposuspension has not been considered in the literature. The two cases
      presented highlight the risk of incontinence and illustrate measures that should
      help to reduce it. The approach aims to reveal potential stress incontinence and
      to prevent excessive stretching of the upper anterior vaginal wall during
      surgical correction. Potential stress incontinence is revealed by a cough stress
      test while reducing the prolapse without a speculum, a 'pessary test' for a few
      days, and urodynamics both with and without a pessary. Patients with potential
      incontinence undergo perineal ultrasound to assess bladder neck position. If
      sacrospinous fixation is used, epidural anesthesia is recommended so as to allow
      the patient to cough during the procedure to ensure accurate suture placement.
      When sacrocolpopexy is done, preoperative assessment of the degree of 'safe
      elevation' ensures accurate suture placement.

PMID- 9657182
TI  - Microvascular decompression of the left lateral medulla oblongata for severe
      refractory neurogenic hypertension.
AB  - OBJECTIVE: To demonstrate that microvascular decompression of the left medulla
      oblongata is a safe and effective modality for treating elevated blood pressure
      in patients with severe medically refractory "essential" hypertension (HTN).
      METHODS: Twelve patients with medically intractable HTN with or without autonomic
      dysreflexia underwent microvascular decompression of the left rostral
      ventrolateral medulla oblongata. Causes such as pheochromocytoma, carcinoid
      syndrome, and renal disease were ruled out before surgery. Indications for
      surgery included systolic blood pressures greater than 180 mm Hg refractory to
      three or more medications, severe blood pressure lability, or medically resistant
      HTN at systolic pressures greater than 160 mm Hg associated with autonomic
      dysreflexia and/or magnetic resonance images demonstrating left medullary
      compression. The median age and follow-up duration were 51 years and 4.1 years,
      respectively. RESULTS: Ten of 12 patients experienced reductions in systolic
      blood pressure greater than 20 mm Hg. Of these 10 patients, pressure reductions
      were temporary (6 mo) in two. Seven of eight patients experienced improvement in
      blood pressure lability and/or autonomic dysreflexia, with five patients showing
      sustained improvements. CONCLUSION: Microvascular decompression of the left
      rostral ventrolateral medulla oblongata may be an effective treatment modality
      for patients suffering from severe HTN and/or autonomic dysreflexia refractory to
      medical management.

PMID- 9657183
TI  - Hypothermic circulatory arrest in neurovascular surgery: evolving indications and
      predictors of patient outcome.
AB  - OBJECTIVE: One of the largest contemporary neurosurgical experiences with
      hypothermic circulatory arrest was analyzed for trends in patient selection and
      clinical variables affecting outcome. METHODS: During a 12-year period, 60
      patients underwent 62 circulatory arrest procedures: 54 had posterior circulation
      aneurysms, 4 had anterior circulation aneurysms, and 2 had other lesions
      (hemangioblastoma and vertebral artery atherosclerosis). RESULTS: The surgical
      morbidity and mortality rates associated with hypothermic circulatory arrest were
      13.3 and 8.3%, respectively. At late follow-up, 76% of the patients had good
      outcomes (Glasgow Outcome Scale scores of 1 and 2), 5% had poor outcomes (Glasgow
      Outcome Scale scores of 3 and 4), and 18% had died. After 1992, circulatory
      arrest was limited to posterior circulation aneurysms and included increasing
      numbers of basilar trunk aneurysms. Patient outcome correlated with preoperative
      neurological condition (admission Glasgow Coma Scale score, P < 0.001; Hunt and
      Hess grade, P = 0.037; and age, P = 0.007). Preservation of perforating arteries
      was paramount to achieving a good outcome (P = 0.005); duration of circulatory
      arrest was not. CONCLUSION: Current indications for hypothermic circulatory
      arrest include only giant and complex posterior circulation aneurysms that cannot
      be treated using conventional techniques or that recur after endovascular
      coiling. Surgical morbidity and mortality rates reflect the increasing complexity
      of the aneurysms treated but are still more favorable than the natural history of
      these lesions. This experience demonstrates that management in specialized
      neurovascular centers can minimize the morbidity associated with circulatory
      arrest so that it remains a viable treatment option for complex posterior
      circulation aneurysms.

PMID- 9657184
TI  - Risk factors for multiple intracranial aneurysms.
AB  - OBJECTIVE: Risk factors that predispose to the formation of multiple intracranial
      aneurysms, which are present in up to 34% of patients with intracranial
      aneurysms, are not well defined. In this study, we examined the association
      between known risk factors for cerebrovascular disease and presence of multiple
      intracranial aneurysms. METHODS: We reviewed the medical records and results of
      conventional angiography in all patients with a diagnosis of intracranial
      aneurysms admitted to the Johns Hopkins University hospital between January 1990
      and June 1997. We determined the independent association between various
      cerebrovascular risk factors and the presence of multiple aneurysms using
      logistic regression analysis. RESULTS: Of 419 patients admitted with intracranial
      aneurysms (298 ruptured and 121 unruptured), 127 (30%) had multiple intracranial
      aneurysms. In univariate analysis, female gender (odds ratio [OR] = 1.9; 95%
      confidence interval [CI], 1.1-3.3) and cigarette smoking at any time (OR = 1.8;
      95% CI, 1.1-3.0) were significantly associated with presence of multiple
      aneurysms. In the multivariate analysis, cigarette smoking at any time (OR = 1.7;
      95% CI, 1.1-2.8) and female gender (OR = 2.1; 95% CI 1.2-3.5) remained
      significantly associated with multiple aneurysms. Hypertension, diabetes
      mellitus, and alcohol and illicit drug use were not significantly associated with
      presence of multiple aneurysms. CONCLUSION: Cigarette smoking and female gender
      seem to increase the risk for multiple aneurysms in patients predisposed to
      intracranial aneurysm formation. Further studies are required to investigate the
      mechanism underlying the association between cigarette smoking and intracranial
      aneurysm formation.

PMID- 9657185
TI  - Treatment of hemangioblastomas in von Hippel-Lindau disease with linear
      accelerator-based radiosurgery.
AB  - OBJECTIVE: Stereotactic radiosurgery is increasingly being used to treat
      hemangioblastomas, particularly those that are in surgically inaccessible
      locations or that are multiple, as is common in von Hippel-Lindau disease. The
      purpose of this study was to retrospectively evaluate the effectiveness of
      radiosurgery in the treatment of hemangioblastomas. METHODS: From 1989 to 1996,
      29 hemangioblastomas in 13 patients with von Hippel-Lindau disease were treated
      with linear accelerator-based radiosurgery. The mean patient age was 40 years
      (range, 31-57 yr). The radiation dose to the tumor periphery averaged 23.2 Gy
      (range, 18-40 Gy). The mean tumor volume was 1.6 cm3 (range, 0.07-65.4 cm3).
      Tumor response was evaluated in serial, contrast-enhanced, computed tomographic
      and magnetic resonance imaging scans. The mean follow-up period was 43 months
      (range, 11-84 mo). RESULTS: Only one (3%) of the treated hemangioblastomas
      progressed. Five tumors (17%) disappeared, 16 (55%) regressed, and 7 (24%)
      remained unchanged in size. Five of nine patients with symptoms referable to
      treated hemangioblastomas experienced symptomatic improvement. During the follow
      up period, one patient died as a result of progression of untreated
      hemangioblastomas in the cervical spine. Three patients developed radiation
      necrosis, two of whom were symptomatic. CONCLUSION: Although follow-up monitoring
      is limited, stereotactic radiosurgery provides a high likelihood of local control
      of hemangioblastomas and is an attractive alternative to multiple surgical
      procedures for patients with von Hippel-Lindau disease.

PMID- 9657186
TI  - Somatosensory evoked potential monitoring during positioning of the patient for
      posterior fossa surgery in the semisitting position.
AB  - OBJECTIVE: Midcervical flexion myelopathy is a rare but well-known complication
      of posterior fossa surgery. To reduce the risk, we routinely used somatosensory
      evoked potential (SSEP) monitoring during positioning of the patient. METHODS:
      Fifty-five consecutive patients were operated on for posterior fossa lesions in
      the semisitting position via a median (5 patients) or a lateral (50 patients)
      suboccipital approach. During positioning, monitoring of SSEPs by stimulation of
      the tibial nerve (T-SSEP) as well as by stimulation of the median nerve (M-SSEP)
      was established. In the case of pronounced SSEP changes, the head was
      repositioned. Surgery was started after SSEP recordings were unchanged as
      compared to the baseline investigation. RESULTS: Effective monitoring was
      possible in all cases. Whereas M-SSEP recordings showed no changes while placing
      patients in the sitting position, T-SSEP recordings were altered in 14 cases
      (25%). In cases using the midline approach, SSEP changes were never so pronounced
      to require repositioning of the head. Head flexion and rotation resulted in
      significant changes of T-SSEP recordings in eight patients (14.5%), requiring
      repositioning. In two cases, an amplitude loss was noted. In only two of these
      eight patients were M-SSEP recordings markedly changed. SSEP recordings after
      repositioning disclosed recovery of spinal cord function. In no patient were
      clinical signs of myelopathy observed postoperatively. CONCLUSION: We observed a
      high incidence of pronounced changes of T-SSEP recordings when the patient's head
      was flexed and rotated for lateral suboccipital craniotomy in the semisitting
      position. Despite the low specificity monitoring of T-SSEPs during positioning of
      the patient for posterior fossa surgery, the semisitting position is strongly
      recommended.

PMID- 9657187
TI  - Cervical spondylotic myelopathy: surgical results and factors affecting
      prognosis.
AB  - OBJECTIVE: A variety of factors may affect surgical outcome in patients with
      cervical spondylotic myelopathy. The aim of this study is to determine these
      factors on the basis of preoperative radiological and clinical data. METHODS: To
      assess the factors affecting postoperative outcome after surgery for cervical
      spondylotic myelopathy, the clinical and radiological data of 27 patients with
      cervical spondylotic myelopathy were reviewed. Functional and neurological
      statuses were assessed using the Japanese Orthopaedic Association (JOA) scale
      modified by Benzel. In all patients, the effect of age, symptom duration,
      cervical curvature, presence or absence of preoperative high signal intensity
      within the spinal cord as revealed by T2-weighted magnetic resonance imaging, and
      diameters of the spinal canal and vertebral body on pre- and postoperative
      neurological statuses were investigated. Plain radiographs were obtained for all
      patients, magnetic resonance images for 21 patients (77.8%), computed tomographic
      scans for 13 patients (48.1%), myelograms for 6 patients (22.2%), and computed
      tomographic myelograms for 4 patients (14.8%). There were five patients with a
      JOA score of 10, six patients with a JOA score of 11, six patients with a JOA
      score of 12, four patients with a JOA score of 13, four patients with a JOA score
      of 14, one patient with a JOA score of 15, and one patient with a JOA score of
      16. All patients underwent cervical laminectomies. The mean follow-up period was
      54.1 months. The final neurological examinations revealed improvement in the JOA
      scores of 85.1 % of the patients. RESULTS: Statistical analysis of all patients
      revealed mean JOA scores of 12.185 +/- 1.618 and 14.370 +/- 2.15 before surgery
      and at final examination, respectively. The difference between the preoperative
      JOA score and the final JOA score was determined to be statistically significant
      (P < 0.0001). Statistical analyses also showed better neurological improvement in
      patients younger than 60 years and in patients with normal preoperative cervical
      lordosis. Although patients without preoperative high signal intensity of the
      spinal cord showed a better improvement rate than did patients with preoperative
      high signal intensity, the determined difference was statistically insignificant.
      CONCLUSION: It can be concluded that age and abnormal cervical curvature predict
      less postoperative neurological improvement. The presence of preoperative high
      signal intensity within the spinal cord may also reflect less neurological
      improvement.

PMID- 9657188
TI  - A prospective randomized study of anterior single-level cervical disc operations
      with long-term follow-up: surgical fusion is unnecessary.
AB  - OBJECTIVE: After 40 years of experience with anterior cervical operations,
      whether to fuse is still controversial. This study seeks to answer this question.
      METHODS: In this prospective randomized study, we operated on 91 patients with
      single-level cervical root compression using three different methods: 1)
      discectomy without fusion, 2) fusion with autologous bone graft, and 3) fusion
      with autologous bone graft plus plating. RESULTS: After 4 years of follow-up, the
      radiological results indicated that complete bony union was achieved in almost
      all cases. A slight kyphosis developed in 62.5% of the patients who had undergone
      discectomy, 40% of the patients who had undergone fusion, and 44% of the patients
      who had undergone fusion plus plating (not significant). The clinical outcomes
      were good for 76% of the patients who had undergone discectomy, 82% who had
      undergone fusion, and 73% who had undergone fusion plus plating. The outcomes
      were poor in 0, 4, and 4%, respectively (not significant). CONCLUSION: According
      to this study, satisfactory results can be achieved by performing simple
      discectomy to treat single-level cervical root compressive disease.

PMID- 9657189
TI  - Neurogenic sarcomas: experience at the University of Toronto.
AB  - OBJECTIVE: Elucidation of the natural history and optimal management of
      neurogenic sarcomas is not straightforward, because of diagnostic difficulties
      and the low incidence of this disease. The majority of neurogenic sarcomas are
      categorized and treated as soft tissue sarcomas, and only a few centers have
      sufficient experience to add to our understanding of these malignant tumors. This
      article proposes an algorithm for the management of these tumors. METHODS: A
      cohort of 18 cases of neurogenic sarcoma (overall mean follow-up period after
      oncological diagnosis, 33.7 mo), representing approximately 3% of all soft tissue
      sarcomas treated at the University of Toronto Musculoskeletal Oncology Unit
      (Toronto, Canada) between 1989 and 1995, were reviewed. The clinical and
      pathological criteria used to establish the diagnosis of neurogenic sarcoma, the
      presenting symptoms, the tumor size and grade, the ability to obtain tumor-free
      margins during en bloc resection, the time to recurrence, and the overall
      survival rates were noted. A centralized pathological review of the biopsy was
      undertaken in all cases. RESULTS: A metastatic survey demonstrated localized
      disease for 16 of the 18 patients. The overall management strategy for these 16
      neurogenic sarcomas with localized disease was to obtain local control by en bloc
      resection. Tumor size, tumor grade, and, most importantly, the ability to obtain
      tumor-free margins were all relevant prognostic factors for survival. Tumor-free
      surgical margins were obtained for 11 of 16 patients, with 9 of these 11 patients
      remaining disease-free. In contrast, all patients for whom tumor-free margins
      could not ultimately be achieved died as a result of their disease. CONCLUSION:
      Based on our experience, we propose an algorithm for the management of these rare
      tumors, for both optimal patient care and oncological research.

PMID- 9657190
TI  - Postcontrast magnetic resonance imaging to predict progression of traumatic
      epidural and subdural hematomas in the acute stage.
AB  - OBJECTIVE: We investigated the possibility of predicting the progression of
      traumatic epidural hematomas (EDHs) and subdural hematomas (SDHs), in the acute
      stage, by using postcontrast magnetic resonance imaging (MRI) with gadolinium
      diethylenetriaminepentaacetic acid. METHODS: From January 1990 through December
      1996, 41 patients with 43 hematomas (21 EDHs and 22 SDHs) underwent postcontrast
      MRI within 24 hours after injury. T1-weighted MRI was performed by using the spin
      echo method, after the administration of 0.1 mmol/kg gadolinium
      diethylenetriaminepentaacetic acid, immediately after computed tomographic
      scanning. RESULTS: All of the enhanced hematomas were enlarged, whereas
      nonenhanced hematomas, except for two SDHs with bleeding tendencies, remained
      unchanged or decreased in volume. The prediction rates for enlargement with this
      method were 100% (21 of 21) for EDHs and 91.0% (20 of 22) for SDHs. The
      sensitivity of this test in predicting enlargement was 100% (15 of 15) for EDHs
      and 81.8% (9 of 11) for SDHs. The specificity was 100% for both types of
      hematomas. The enlargement rates for diffusely enhanced hematomas were
      statistically greater than those for nonenhanced hematomas. All of the patients
      with diffusely enhanced hematomas, which were found during surgery to exhibit
      active bleeding points, experienced consciousness deterioration. CONCLUSION: We
      conclude that diffuse enhancement indicates extravasation from broken vessels
      that continue to bleed and that diffusely enhancing hematomas will be rapidly
      enlarged. We think that postcontrast MRI can be very useful for predicting the
      progression of acute EDHs and SDHs.

PMID- 9657191
TI  - Untreated growing cranial fractures detected in late stage.
AB  - OBJECTIVE: Because the great majority of published cases of treated growing
      cranial fractures (GCFs) involved infants and children, the natural evolution of
      untreated GCFs is not well known. The question of whether untreated GCFs may
      cause progressive neurological deficits is controversial. METHODS: This
      retrospective study is of GCFs treated between 1989 and 1997. Nine patients
      (eight male patients and one female patient; median age, 20.5 yr) with GCFs who
      underwent surgical intervention during the late stage are presented. The dural
      and cranial defects were repaired, and additional decompressive surgical
      procedures (cyst fenestration, n = 6; cyst excision, n = 1; cyst excision with
      cystoperitoneal shunting, n = 2) were performed for all patients. This is the
      largest of the published series. RESULTS: All of the patients had histories of
      severe head trauma that occurred during childhood. The average age at the time of
      the onset of symptoms was approximately 13.1 years, and the interval between head
      injury and first symptom ranged from 8 to 13 years. All of the patients had lytic
      lesions in the cranium. Headache was the most common symptom, and of eight
      patients, seven improved completely and one improved partially. One of four
      epileptic patients was seizure-free postoperatively. None of the paresis
      improved, except in one patient. CONCLUSION: We conclude that untreated GCFs may
      cause delayed onset neurological manifestations in addition to cranial growth
      asymmetry. GCFs, discovered incidentally in adolescence or adulthood without any
      neurological deficits, should be operated on as soon as feasible to prevent
      further brain destruction. Cranioplasty with dural repair, in addition to cyst
      fenestration, should be considered as the essential procedure for the treatment
      of these lesions.

PMID- 9657192
TI  - Resection and graft repair for localized hypertrophic neuropathy.
AB  - OBJECTIVES: Formulation of surgical management recommendations for localized
      hypertrophic mononeuropathy has been difficult because of the infrequency of the
      lesion, lack of precise pathological diagnosis, and uncertainties regarding its
      cause. The purpose of this retrospective review of the Louisiana State University
      (LSU) experience with this unusual neuropathy was to evaluate the efficacy of
      lesion resection and interposition grafting in its management. METHODS: The
      charts of 15 patients operated on at LSU during a 15-year period with a
      pathological diagnosis of localized hypertrophic neuropathy were reviewed.
      RESULTS: Hypertrophic lesions were located on major named peripheral nerves of
      the extremities, distributed equally to the upper and lower extremities. Family
      history was negative for all patients, and entrapment or trauma, other than
      previous surgery, were unlikely by symptom location or history. Weakness was the
      most common presentation. The mean length of symptoms was 76 months. Atrophy,
      sensory loss, Tinel's sign, focal tenderness, and a mass were found in the
      majority of patients. Preoperative electrophysiological studies showed chronic
      denervational changes in all patients. At surgery, if no action potential or one
      of low amplitude was recorded across the lesion, the lesion was resected and an
      autologous nerve graft measuring from 3.5 to 8.5 cm in length was interposed.
      During follow-up periods of 1 or more years, seven of nine patients with
      localized hypertrophic mononeuropathy treated with graft repairs were either
      unchanged or improved. CONCLUSION: Localized hypertrophic mononeuropathy is a
      progressive process associated with pathological nerve changes that correlate
      with eventual severe functional loss. If intraoperative histological examination
      shows onion bulb neuropathy and intraoperative nerve action potentials confirm a
      nonfunctioning or poorly functioning segment, lesion resection with interposition
      graft repair provides the possibility of some degree of recovery.

PMID- 9657193
TI  - The anterior subtemporal, medial transpetrosal approach to the upper basilar
      artery and ponto-mesencephalic junction.
AB  - OBJECTIVE: To describe and anatomically analyze the amount of exposure provided
      by an anterior subtemporal, medial transpetrosal approach to access the upper
      third of the basilar artery, ventral mesencephalon, pons, and posterior cavernous
      sinus. PATIENTS AND METHODS: The outcomes of six patients who underwent surgical
      treatment via the anterior subtemporal, medial transpetrosal approach at our
      institution during the past 2 years were reviewed. The series included three
      patients with subarachnoid hemorrhage from low-lying basilar apex aneurysms, one
      patient with intraparenchymal hemorrhage from a pontine cavernous malformation,
      and two patients with slowly progressive cranial neuropathies secondary to
      petroclival tumors. Thirty dry temporal bone specimens were also measured to
      quantify the height of petrous bone resection and added proximal basilar artery
      exposure. RESULTS: The surgical exposure was greatly enhanced in each instance,
      allowing each lesion to be treated in a straightforward manner with minimal added
      morbidity (one trochlear nerve palsy, one worsening of a preexistent oculomotor
      nerve palsy). Our subsequent morphometric analysis indicates that an additional 1
      to 1.5 cm of basilar artery, clivus, and pons exposure over that of a standard
      anterior subtemporal approach is provided by this technique. CONCLUSION: This
      approach combines the wide view of the subtemporal approach with the more
      proximal exposure afforded by a medial petrosectomy. The widened visualization of
      the ventral pons and mesencephalon minimizes cranial nerve morbidity, greatly
      facilitates dissection of low-lying aneurysms, and provides proximal basilar
      artery control that would otherwise be obscured by the petrous ridge.

PMID- 9657194
TI  - Influence of isoflurane on myogenic motor evoked potentials to single and
      multiple transcranial stimuli during nitrous oxide/opioid anesthesia.
AB  - OBJECTIVE: Transcranial motor evoked potentials (tc-MEPs) are used to monitor the
      spinal cord intraoperatively. Volatile anesthetics considerably depress
      amplitudes of tc-MEPs. This study was undertaken to determine whether multipulse
      stimulation might overcome this depressant effect. METHODS: In 10 patients
      undergoing spinal surgery, incremental doses of isoflurane were added to a
      nitrous oxide/opioid anesthetic regimen and maintained constant at 0.2, 0.4, and
      0.6% end tidal for at least 15 minutes. tc-MEP responses to single-pulse and
      trains of three and five (interstimulus interval, 2 ms) transcranial electrical
      stimuli were recorded from the tibialis anterior muscles. RESULTS: Before the
      addition of isoflurane, tc-MEPs were recordable in all patients, even with single
      pulse stimuli (median amplitude, 428 microV). With 0.2% end-tidal isoflurane, tc
      MEPs were recordable in eight patients with single-pulse stimulation and in all
      patients with three and five successive stimuli. At 0.4% isoflurane, responses
      were recordable in only one patient using single-pulse stimuli and in all
      patients using three and five stimuli. With 0.6% isoflurane, tc-MEPs to trains of
      three and five stimuli were recordable in all patients except one. The amplitude
      of the responses obtained with 0.2, 0.4, and 0.6% end-tidal isoflurane was
      significantly smaller than that of control responses (P < 0.05). CONCLUSION:
      These data suggest that despite the powerful depressant effects of isoflurane on
      myogenic motor responses, tc-MEP monitoring during isoflurane anesthesia may be
      feasible, provided that multipulse stimulation paradigms are used and the
      concentration of isoflurane does not exceed 1 minimal anesthetic concentration
      unit.

PMID- 9657195
TI  - Hemodynamic changes in arterial feeders and draining veins during embolotherapy
      of arteriovenous malformations: an experimental study in a swine model.
AB  - OBJECTIVE: Transcatheter assessment of changes in draining vein (DV) flow
      velocity has been proposed recently as a potentially useful procedure for
      hemodynamic monitoring of the progression of embolotherapy in cerebral
      arteriovenous malformations (AVMs). We compared and contrasted changes in
      hemodynamic parameters of arterial feeders (AFs) and DVs during experimental AVM
      embolotherapy. METHODS: Carotid-jugular fistula-type AVM models were surgically
      created in eight swine. Pre- and postembolization transcatheter mean AF and DV
      pressures, DV-time average spectral peak velocity, and AF and DV pulsatility
      indices were assessed. An expression, the peak systolic velocity minus end
      diastolic velocity (Vs - Ved), was also used in evaluating the transvenous
      Doppler spectra. Pre- and postembolization hemodynamic parameters were compared
      statistically. RESULTS: Pre-embolization DV flow was pulsatile (Vs - Ved, 12 +/-
      4.8 cm/s), with a mean DV velocity of 39.3 +/- 11.4 cm per second.
      Postembolization, this changed to a less/nonpulsatile pattern (Vs - Ved, 5.4 +/-
      2.7 cm/s; P = 0.0035) with a lower mean DV-average spectral peak velocity of 7.0
      +/- 3.1 cm per second (P = 0.0001). The mean DV pressure was also reduced from
      52.0 +/- 8.2 to 45.5 +/- 8.7 mm Hg (P = 0.0023). The mean AF pressure increased
      from a mean of 79.5 +/- 15.5 to 96.8 +/- 16.2 mm Hg (P = 0.0004). The DV
      pulsatility index values also increased from a mean of 0.3 +/- 0.2 to 1.1 +/- 0.5
      (P = 0.0003). Periembolization objective hemodynamic changes were detected in the
      DVs earlier than were the visually subjective angiographic changes observed
      within the nidus. CONCLUSION: This preliminary study indicates that transvenous
      assessment of average spectral peak velocity and wave pattern (Vs - Ved) may be
      useful in the hemodynamic evaluation of AVM shunting. The convergence of these
      two parameters to a range less than 10 cm per second after nidus embolization may
      afford a theoretical advantage over AF pressure measurements when used for
      objective and quantitative monitoring of endovascular embolotherapy.

PMID- 9657196
TI  - Specific inhibition of apoptosis after cold-induced brain injury by moderate
      postinjury hypothermia.
AB  - OBJECTIVE: Apoptosis of neuronal cells plays a key role in many developmental and
      pathological processes of the central nervous system. Deoxyribonucleic acid (DNA)
      of cells undergoing apoptosis is cleaved by an endonuclease into oligonucleosoma
      sized fragments. These fragments can be labeled using in situ terminal
      deoxynucleotidyl transferase so that the apoptotic cells can be visualized by in
      situ apoptotic staining. The model of cold-induced rat brain edema was used to
      further examine this hypothesis. The protective effect of hypothermia was also
      studied in this model of cold-induced brain injury. METHODS: Using a terminal
      deoxynucleotidyl transferase-mediated deoxyuridine 5'-triphosphate-biotin nick
      end labeling technique, the neuronal cells with DNA fragmentation in different
      regions of the brains of rats subjected to cold-induced brain injury were
      detected. The internucleosomal fragments of DNA in apoptotic cells were examined
      using agarose gel electrophoresis. The animals were randomly divided into three
      groups: 1) sham (n = 8); 2) cold-induced brain injury, killed at 12, 24, 48, 72,
      and 168 hours after cold lesion (n = 10 for each time point); 3) hypothermia,
      both mean temporalis and rectal temperatures were reduced by surface cooling to
      32 degrees C (standard deviation, 0.1 degrees C) for 3, 6, and 12 hours (n = 10
      for each time point) beginning 1 hour after cold-induced brain injury. RESULTS:
      The apoptotic cells were detectable for up to 72 hours after the initial brain
      injury and reached a peak at approximately 24 to 48 hours, with a mean peak value
      of 24.29 +/- 5.26, 15.37 +/- 4.10, 15.81 +/- 3.56, 13.94 +/- 2.48, 10.46 +/-
      2.23, and 7.68 +/- 2.48% in the cortex, subcortex, white matter, CA1, CA3, and
      dentate gyrus, respectively, and had a significant increase, compared with the
      control value (mean +/- standard error, P < 0.01). Agarose gel electrophoresis of
      DNA extracted from cortex and hippocampus containing apoptotic cells revealed a
      "DNA ladder" at 180- to 200-base pair intervals. In animals subjected to the same
      brain injury that underwent 32 degrees C hypothermia, the numbers of apoptotic
      cells were reduced evidently and DNA fragmentation was inhibited. CONCLUSION: The
      data suggest that apoptosis occurs after cold-induced brain injury and that DNA
      fragmentation may be associated with apoptotic cell death. Moderate hypothermia
      shows specific effect on inhibition of apoptotic cell death and cellular DNA
      fragmentation after cold-induced brain injury in rats.

PMID- 9657197
TI  - Tamoxifen inhibits GH3 cell growth in culture via enhancement of apoptosis.
AB  - OBJECTIVE: To investigate the antitumor effects of tamoxifen on pituitary tumor
      GH3 cells, which lack receptors for dopamine. METHODS: GH3 cells were treated
      with tamoxifen (10(-7) mol/L), bromocriptine (10(-8) mol/L), or a combination of
      tamoxifen and bromocriptine in serum-free media. The cell number,
      bromodeoxyuridine (BrdU) labeling ratio, and apoptotic ratio were assessed.
      Prolactin (PRL) expression was examined using immunocytochemistry and Western
      blot analysis. RESULTS: After tamoxifen treatment for 4 days, the cell number
      decreased to 53.0% of that of untreated control cells. The percentage of PRL
      immunoreactive GH3 cells decreased to 2.9%, versus 8.6% of untreated control
      cells, which was compatible with the results of Western blot analysis for PRL.
      Apoptosis increased to approximately three times that of untreated control cells
      at Day 2 of treatment, whereas no significant change was shown in BrdU
      incorporation. These effects by tamoxifen were not observed in the simultaneous
      treatment with 17beta-estradiol. Bromocriptine did not change the cell number,
      BrdU incorporation, the apoptotic ratio, or the percentage of PRL-positive cells,
      and it was also shown that tamoxifen did not change the sensitivity of GH3 cells
      to bromocriptine treatment. CONCLUSION: Tamoxifen, an antiestrogen, exerts its
      antitumor effect on GH3 cells in two ways: by suppression of cell growth and by
      causing a decrease in PRL. Apoptosis seems to contribute to the inhibition of GH3
      cell growth.

PMID- 9657198
TI  - Inhibition of Ras and related G-proteins as a therapeutic strategy for blocking
      malignant glioma growth.
AB  - OBJECTIVE: Preliminary studies have demonstrated that the Ras family and related
      guanosine 5'-triphosphate-dependent proteins (G-proteins) are overactivated in
      malignant gliomas and may function as indirect mediators of glial transformation
      initiated by deregulated upstream signaling elements. We postulated that
      inhibiting the activation of such proteins might represent a promising strategy
      for blocking the aberrant proliferation of these tumors. METHODS AND RESULTS:
      Accordingly, we examined the therapeutic efficacy against malignant glioma cells
      in vitro of a series of selective peptidomimetic inhibitors of farnesylation (FTI
      277) and geranylgeranylation (GGTI-286 and GGTI-298), which are critical steps in
      the post-translational processing (prenylation) of these proteins. We first
      defined concentration-response relationships for each of these agents, using MTS
      based cell proliferation assays in the established malignant glioma cell lines U
      87 and LN-Z308 and the low-passage malignant glioma cell line SG-388. FTI-277,
      GGTI-286, and GGTI-298 each produced a striking concentration-dependent
      antiproliferative effect on the glioma cell lines, with the median effective dose
      ranging from 2.5 to 15.5 micromol/L. We then assessed the effect of prenylation
      inhibition on cell viability using clonogenic growth assays. This demonstrated a
      steady drop in the number of colonies with increasing drug concentrations for all
      three inhibitors. Third, we examined whether the cytotoxic effects of one of
      these inhibitors (GGTI-298) were associated with the induction of apoptosis using
      a terminal transferase-catalyzed in situ end-labeling technique. This approach
      showed a time-dependent increase in apoptotic cell numbers, which correlated with
      a progressive decrease in the percentage of cells that were viable as assessed by
      trypan blue exclusion. CONCLUSION: Our studies demonstrated that FTI-277, GGTI
      286, and GGTI-298 each yielded significant antiproliferative effects in human
      malignant glioma cells in vitro at low micromolar concentrations, which have been
      achievable in vivo without major systemic toxicity. Extended periods of drug
      treatment produced cytotoxicity in the tumor cells, which correlated with the
      induction of apoptosis. We conclude that inhibition of Ras and related G-proteins
      offers a promising approach for blocking glioma proliferation that justifies
      further investigation in vivo.

PMID- 9657199
TI  - Neurosurgery at the University of Virginia.
AB  - Before 1937, members of the Department of Surgery and Gynecology practiced
      emergency neurosurgery at the University of Virginia in the same fashion as in
      other hospitals in the United States. In 1937, Claude C. Coleman, Chairman of the
      Department of Neurosurgery at the Medical College of Virginia in Richmond,
      organized a Division of Neurosurgery as part of the Department of Surgery and
      Gynecology at the University of Virginia. He designated one of his staff members,
      John M. Meredith, as Neurosurgeon-in-charge. Dr. Coleman served as Clinical
      Professor of Neurological Surgery at the University of Virginia from 1937 to
      1941, while also working in Richmond. This arrangement attracted increasing
      numbers of patients, leading to the formation of a separate department, under the
      direction of William Gayle Crutchfield, in 1941. In conjunction with Juan de Dios
      Martinez-Galindo, who joined the faculty in 1943, Dr. Crutchfield built and
      directed the neurosurgical training program until his retirement. In 1969, John
      A. Jane, Sr., became Professor and Chairman of the Department of Neurosurgery.
      Pursuing the Jeffersonian intent of attracting "... those of due degree of
      science and of talents for instruction," the Department has been enhanced by the
      arrival of Neal F. Kassell in 1984, Ladislau Steiner in 1987, Edward R. Laws,
      Jr., in 1992, Dheerendra Prasad in 1995, Gregory Helm in 1996, and Mark Shaffrey
      in 1997. Resident training has been a priority of the Department of Neurosurgery;
      many academic neurosurgeons were trained and practiced their specialty in the
      Department early in their careers. Sixty years after its foundation, the
      Department of Neurosurgery continues its commitment to patient care, research,
      and the "... instruction of those who come after us."

PMID- 9657200
TI  - Perspectives on neurosurgical practice: neurosurgery in Jordan.
AB  - Neurosurgery as a specialty medical field is new in Jordan. This article
      documents the history, current status, and projected future of neurosurgery in
      Jordan. Resident training is also highlighted, and challenges for the future of
      the profession are presented.

PMID- 9657201
TI  - Granulomatous hypophysitis caused by a ruptured intrasellar Rathke's cleft cyst:
      report of a case and review of the literature.
AB  - OBJECTIVE AND IMPORTANCE: Ruptured Rathke's cleft cyst is a rare cause of giant
      cell granulomatous hypophysitis. Chronic inflammatory reaction is caused by
      extravased cyst content into the adjacent gland. We provide a demonstration that
      mucins produced by cells lining the cyst wall caused the granulomatous giant cell
      reaction. CLINICAL PRESENTATION: A 37-year-old nonpregnant woman presented with a
      3-year-history of headache and amenorrhea. She had experienced normal sexual
      maturation, and her medical history was unremarkable. Radiologically, the lesion
      appeared as an intrasellar mass with a cystic component indistinguishable from a
      pituitary adenoma with cystic degeneration. TECHNIQUE: The patient underwent a
      transsphenoidal approach. Because no demarcation between normal and affected
      tissue was evident at surgery, the lesion and residual pituitary were radically
      removed. Tissue was studied using routine hematoxylin and eosin and histochemical
      stainings for mucins and immunocytochemical techniques. CONCLUSION: This study
      demonstrates that mucins that had spilled out from the cyst caused the
      granulomatous reaction. Using computed tomography, magnetic resonance imaging,
      and gross inspection, distinction between granulomatous hypophysitis and
      pituitary adenoma was virtually impossible. Nevertheless, a granulomatous
      reaction of the pituitary gland should be suspected in a case of a sellar mass
      having a cystic area. In such cases, intraoperatory diagnosis on frozen sections
      is mandatory because adoption of a conservative treatment allows preservation of
      the gland.

PMID- 9657202
TI  - Spontaneous shrinkage of lumbosacral lipoma in conjunction with a general
      decrease in body fat: case report.
AB  - OBJECTIVE AND IMPORTANCE: We describe a rare case of a lumbosacral lipoma that
      shrank spontaneously in parallel to a general loss of body fat. Although early
      prophylactic surgery is generally recommended for lumbosacral lipomas, the
      observation made in this case may provide an important implication regarding the
      conservative management of this disorder. CLINICAL PRESENTATION: A 9-year-old
      male patient with a subcutaneous lipoma at the sacral level was found to have a
      lumbosacral lipoma in the spinal canal and tethered spinal cord, as revealed by
      magnetic resonance imaging. The patient showed no neurological or urological
      deficits, except for a mild pes cavus deformity. INTERVENTION: Follow-up magnetic
      resonance imaging performed 4 years later revealed a significant decrease in the
      size of the lumbosacral lipoma. The patient became very thin and showed no
      neurological deterioration during the follow-up period. The shrinkage of the
      lipoma was considered to be in association with the general loss of body fat.
      CONCLUSION: The control of body weight may be an important factor in the
      conservative management of patients with lumbosacral spinal lipomas.

PMID- 9657203
TI  - Delayed posttraumatic middle cerebral artery vasospasm demonstrated by magnetic
      resonance angiography: case report.
AB  - OBJECTIVE AND IMPORTANCE: Magnetic resonance (MR) angiographic diagnosis is a
      noninvasive method having high sensitivity and specificity in the detection of
      various cerebrovascular disorders. This is the first report of MR angiographic
      detection of delayed posttraumatic middle cerebral artery vasospasm, the
      occurrence of which has been rarely described. CLINICAL PRESENTATION: A 42-year
      old man sustained head trauma in a traffic accident, which caused a right
      subdural hematoma. Even though the hematoma was irrigated through one burr hole
      on Day 10, the patient subsequently developed left hemiparesis in association
      with dysarthria 4 days after surgery. MR angiography demonstrated decreased flow
      signal in the right M1 and M2 portions, suggestive of vasospasm. INTERVENTION:
      The patient underwent intravascular volume expansion/ hemodilution therapy for 3
      days. CONCLUSION: After the therapy, the ischemic symptoms completely
      disappeared. Follow-up study confirmed resolution of the flow signal in the right
      middle cerebral artery. It is suggested that MR angiography is a useful
      noninvasive method in the evaluation of posttraumatic cerebrovascular disorders,
      which constitute important secondary insults in head trauma.

PMID- 9657204
TI  - Diagnosis and monitoring of cerebral hyperfusion after carotid endarterectomy
      with single photon emission computed tomography: case report.
AB  - OBJECTIVE AND IMPORTANCE: Focal neurological deficits after carotid
      endarterectomy may result from ischemia or hyperperfusion. The usefulness of
      single photon emission computed tomography (SPECT) for differentiating between
      these two mechanisms has not been previously emphasized. CLINICAL PRESENTATION:
      An 83-year-old man experienced dysarthria and left-sided weakness immediately
      after undergoing endarterectomy of the right internal carotid artery. The results
      of computed tomography of the head were normal, and transcranial Doppler
      sonography showed symmetrically elevated velocities in both middle cerebral
      arteries. On the 1st postoperative day, the patient's deficits worsened in
      parallel with spontaneous increases in blood pressure, and blood pressure
      reduction with labetalol resulted in clinical improvement. INTERVENTION: On the
      2nd postoperative day, technetium-99-hexametazime SPECT demonstrated markedly
      increased flow in the right basal ganglia and inferior frontal cortex, confirming
      the diagnosis of cerebral hyperperfusion. The patient's deficits continued to
      improve with antihypertensive therapy, and SPECT performed 7 and 48 days after
      surgery showed gradual normalization of the focal hyperemia. CONCLUSION: SPECT
      can be used to diagnose and monitor cerebral hyperperfusion after carotid
      endarterectomy and may be of particular value for differentiating hyperperfusion
      from ischemia when characteristic computed tomographic and transcranial Doppler
      sonographic findings are absent.

PMID- 9657205
TI  - Nontraumatic atlanto-occipital and atlantoaxial rotatory subluxation: case
      report.
AB  - OBJECTIVE AND IMPORTANCE: Concomitant atlantoaxial and atlanto-occipital
      subluxation resulting from any cause is extremely rare. We have found only five
      previously reported cases and describe another, suggesting a treatment plan.
      CLINICAL PRESENTATION: A 13-year-old female patient presented with a 3-month
      history of neck pain and decreased neck movements. All symptoms started after a
      localized neck infection had been treated successfully with antibiotics. There
      was no history of trauma. A diagnosis of postinfective atlanto-occipital and
      atlantoaxial rotatory subluxation was made based on a plain roentgenogram and was
      confirmed based on a computed tomographic scan. INTERVENTION: The atlantoaxial
      and atlanto-occipital subluxation was reduced during surgery. A posterior C1-C2
      fixation was performed, and the atlanto-occipital joint was stabilized by means
      of a halo body jacket for 3 months. One year after removal of the jacket, all
      subluxation remained reduced and the patient retained significant neck movement.
      CONCLUSION: Disruption of the occipito-atlanto-axial complex can result from
      relatively minor head and neck infections and should be suspected in children
      with persisting neck pain and decreased neck movements. It may not be necessary
      to perform an occipitoaxial fusion to treat these patients, and a more limited
      fusion may be successful.

PMID- 9657206
TI  - Distal posterior cerebral artery revascularization in multimodality management of
      complex peripheral posterior cerebral artery aneurysms: technical case report.
AB  - OBJECTIVES AND IMPORTANCE: Although controversial, revascularization of the
      distal posterior cerebral artery (PCA) may become necessary in treating complex
      PCA aneurysms before proximal parent vessel sacrifice. The revascularization of
      the distal PCA territories of two patients with peripheral PCA aneurysms is
      presented. CLINICAL PRESENTATIONS: One patient had an aneurysm of the P2-P3
      segment and failed a selective P2 balloon occlusion test by developing homonymous
      hemianopia before planned parent vessel sacrifice. The other patient with a giant
      P2 segment aneurysm presented with visual field deficits. TECHNIQUE: The distal
      segment of PCA was revascularized before the aneurysms were trapped by surgical
      clipping or coil occlusion of the distal P2 segment, proximal to the aneurysms.
      In both cases, the occipital artery was used as the "donor" vessel. Temporary
      occlusion times were 22 and 20 minutes, respectively. Both grafts were patent on
      postoperative angiography, and both patients had full visual fields at the time
      of their follow-up examinations. CONCLUSION: De novo distal P2 sacrifice,
      advocated for treating peripheral PCA aneurysms, leads to visual field deficits
      in some patients. Revascularization of the distal segment of the PCA, less
      technically demanding than bypass to other PCA segments, preserves blood flow,
      thus sparing vision in this subset of patients.

PMID- 9657207
TI  - Surgical removal of a choroid plexus adenoma using the argon beam coagulator:
      technical case report.
AB  - OBJECTIVE AND IMPORTANCE: Choroid plexus tumors may be extremely vascular,
      limiting surgical resection. A case of a choroid plexus adenoma is presented in
      which the argon beam coagulator (System 6500; ConMed Corp., Utica, NY) was used
      as a surgical adjunct. CLINICAL PRESENTATION: A 12-year-old male patient with a
      giant tumor of the lateral ventricle presented with visual loss and was found to
      have a large intraventricular tumor. At surgery, the tumor was extremely
      vascular, and the pathological finding was consistent with a choroid plexus
      adenoma. TECHNIQUE: Because of its vascularity, the tumor was resected in stages
      with the aid of the argon beam coagulator. CONCLUSION: We conclude that this
      device may have application in selected neurosurgical operations.

PMID- 9657208
TI  - Stereotactic ventriculoperitoneal shunt for idiopathic intracranial hypertension:
      technical note.
AB  - OBJECTIVE: Lumboperitoneal shunting is the bastion of neurosurgical management
      for idiopathic intracranial hypertension (IIH). However, recent studies document
      a high failure rate for this procedure. The present study was designed to explore
      the feasibility of placing ventriculoperitoneal shunts under stereotactic control
      into patients with IIH as an alternative to lumboperitoneal shunting. METHODS:
      Seven patients with IIH for whom medical management had failed underwent
      stereotactic implantation of ventriculoperitoneal shunts. RESULTS: Shunt
      placement was successful and uncomplicated in each case. Five of seven patients
      experienced complete resolution of papilledema. The remaining two patients showed
      resolving papilledema. Six of seven patients experienced resolution of headache.
      The remaining patient continued to have headaches despite a radionuclide study
      demonstrating normal shunt function. CONCLUSION: Our results suggest that
      stereotactic ventriculoperitoneal shunting may be a reasonable alternative to
      lumboperitoneal shunting in those patients with IIH who require surgical
      intervention.

PMID- 9657209
TI  - Library: historical perspective. John Farquhar Fulton.

PMID- 9657210
TI  - John Farquhar Fulton.

PMID- 9657211
TI  - Intramedullary pressure in syringomyelia: clinical and pathophysiological
      correlates of syrinx distension.

PMID- 9657212
TI  - Risk factors for neurosurgical site infections after craniotomy: a prospective
      multicenter study of 2944 patients.

PMID- 9657213
TI  - Profiling of the eye aqueous humor in exfoliation syndrome by high-performance
      liquid chromatographic analysis of hyaluronan and galactosaminoglycans.
AB  - The concentrations of hyaluronan and galactosaminoglycans -- i.e., chondroitin
      sulfate and dermatan sulfate -- were measured in the aqueous humor of the eye
      from patients with exfoliation syndrome and from healthy persons. The
      glycosaminoglycans/proteoglycans were almost completely precipitated (>97%) with
      ethanol in the presence of dextran as carrier and, following enzymic digestion,
      hyaluronan and galactosaminoglycans, were quantitatively converted to delta4,5
      disaccharides. Non-degraded heparan sulfate and proteins/glycoproteins were
      removed by ultrafiltration using a Centricon 3 membrane. Separation and
      determination of hyaluronan- and galactosaminoglycan-derived delta-disaccharides
      were performed by ion-suppression HPLC. For an accurate analysis in triplicate,
      as little as 50 microl of aqueous humor is required. Application of this method
      to the analysis of samples from six patients with exfoliation syndrome and three
      healthy persons showed that hyaluronan levels in patients (6.65-16.15 microg ml(
      1)) were significantly higher (3-8 times) than in healthy persons (2.0-2.24
      microg ml(-1)). There was no significant alteration in the galactosaminoglycan
      concentration. The obtained data open a new area in the deeper understanding of
      the exfoliation syndrome pathophysiology and in establishing a highly sensitivity
      and accurate HPLC method for its diagnosis and patient's follow-up.

PMID- 9657214
TI  - Quantitative detection method of triglycerides in serum lipoproteins and serum
      free glycerol by high-performance liquid chromatography.
AB  - We have developed a simple and reliable method for quantitative detection of
      triglycerides (TG) in serum lipoproteins and serum-free glycerol (FG) by high
      performance liquid chromatography (HPLC). After separation of serum constituents
      using a new gel-permeation column (TSK gel Lipopropak XL, Tosoh) and a new eluent
      (TSK eluent LP-2, Tosoh), TG and FG were detected by on-line reaction using a
      modified reagent which contained glycerol kinase, glycerol-3-phosphate oxidase
      and lipoprotein lipase. HPLC patterns showed five peaks corresponding to
      chylomicrons, very-low-density, low-density, high-density lipoproteins and FG.
      Absolute concentrations of TG in each lipoprotein fraction and serum FG were
      calculated from the corresponding peak areas using standard FG as a calibrator.
      Due to its very high sensitivity of peak detection, this method has become
      desirable for the analyses of lipoproteins of very low concentrations such as in
      cell culture systems. This technique will contribute to a better understanding of
      lipoprotein TG and serum FG distribution in human and nonhuman subjects.

PMID- 9657215
TI  - Salt-independent binding of antibodies from human serum to thiophilic
      heterocyclic ligands.
AB  - Several thiophilic adsorbents with mercaptoheterocyclic ligands have been
      analyzed for their ability to bind human serum proteins in a salt-independent
      way. In contrast to 2-mercaptopyrimidine, 2-mercaptopyridine derived ligands show
      a group-selective binding of immunoglobulins and alpha2-macroglobulin, not only
      in the presence of high concentrations of sodium sulphate but in buffers with low
      ionic strength. The binding is restricted to thiophilic gels obtained by coupling
      2-mercaptopyridine to a vinylsulphone-activated matrix and is not achieved on
      epichlorohydrin-activated gels. A novel thiophilic ligand based on
      mercaptonicotinic acid, containing a carboxylic group together with the
      thiophilic pattern of thioaromatic adsorbents, is demonstrated to be useful as an
      alternative purification scheme for antibodies.

PMID- 9657216
TI  - Validation procedures of sedimentation field-flow fractionation techniques for
      biological applications.
AB  - Sedimentation field-flow fractionation (SdFFF) offers great potential for the
      separation of submicrometer and micrometer-sized species. The availability of
      commercial instrumentation and the versatility of this method originated its
      success. At this stage of development, SdFFF techniques are mature enough for use
      in analytical research, development and even routine work. However, prior to
      their use, these techniques like any other methodologies, have to be validated.
      As the application of SdFFF techniques to cell separation is being constantly
      developed, we have investigated separation performance according to validation
      rules classically defined for separation methods (chromatography) in the case of
      cellular materials.

PMID- 9657217
TI  - Identification of a flunixin metabolite in camel by gas chromatography-mass
      spectrometry.
AB  - A flunixin metabolite, a hydroxylated product, has been identified in camel urine
      and plasma samples using gas chromatography-mass spectrometry (GC-MS) and GC-MS
      MS in the electron impact and chemical ionization modes. Its major fragmentation
      pattern has been verified by GC-MS-MS in daughter ion and parent ion scan modes.
      The method could detect flunixin and its metabolite in camel urine after a single
      intravenous dose of 2.2 mg of flunixin/kg body weight for 96 and 48 h,
      respectively, which increases the reliability of antidoping control analysis.

PMID- 9657218
TI  - Effect of temperature and some common metals on the stability of volatile
      anaesthetic-Entonox mixtures.
AB  - Thermal stability of pressurised ready-to-use volatile liquid anaesthetic
      mixtures (halothane, isoflurane and enflurane) in Entonox (commercially available
      premixed 50% N2O, 50% O2 mixture) were investigated at temperatures of 20, 258,
      400, 503 and 602 degrees C on glass, stainless steel, copper and aluminium by gas
      chromatography and GC-MS. It was found that most of the decomposition products
      formed were halogenated compounds and the observed thermal stabilities in glass,
      stainless steel and copper allowed a thermal treatment up to 250 degrees C
      without any decomposition problem. Aluminium was found to be the most effective
      metal at causing decomposition of the anaesthetic mixtures even at lower
      temperatures.

PMID- 9657219
TI  - Simple analysis of local anaesthetics in human blood using headspace solid-phase
      microextraction and gas chromatography-mass spectrometry-electron impact
      ionization selected ion monitoring.
AB  - A simple method for analysis of five local anaesthetics in blood was developed
      using headspace solid-phase microextraction (HS-SPME) and gas chromatography-mass
      spectrometry-electron impact ionization selected ion monitoring (GC-MS-EI-SIM).
      Deuterated lidocaine (d10-lidocaine) was synthesized and used as a desirable
      internal standard (I.S.). A vial containing a blood sample, 5 M sodium hydroxide
      and d10-lidocaine (I.S.) was heated at 120 degrees C. The extraction fiber of the
      SPME system was exposed for 45 min in the headspace of the vial. The compounds
      adsorbed on the fiber were desorbed by exposing the fiber in the injection port
      of a GC-MS system. The calibration curves showed linearity in the range of 0.1-20
      microg/g for lidocaine and mepivacaine, 0.5-20 microg/g for bupivacaine and 1-20
      microg/g for prilocaine in blood. No interfering substances were found, and the
      time for analysis was 65 min for one sample. In addition, this proposed method
      was applied to a medico-legal case where the cause of death was suspected to be
      acute local anaesthetics poisoning. Mepivacaine was detected in the left and
      right heart blood samples of the victim at concentrations of 18.6 and 15.8
      microg/g, respectively.

PMID- 9657220
TI  - Gas chromatography-mass spectrometric method for quantitative determination in
      human urine of dicarboxylic (dioic) acids produced in the body as a consequence
      of cholesterol biosynthesis inhibition.
AB  - A capillary gas chromatography-mass spectrometric (GC-MS) method in human urine
      has been developed and validated for the quantitative determination of
      dicarboxylic acids (dioic acids) which are produced in the body as a consequence
      of the administration of an inhibitor of the enzyme squalene synthase, which is
      involved in the biosynthesis of cholesterol. The standards and quality control
      (QC) samples were prepared by adding dioic acids into human urine. Internal
      standard (sebacic acid) was added to each urine sample (0.1 ml) and then dried by
      evaporation under nitrogen. The dried sample was reacted with pentafluorobenzyl
      (PFB) bromide under conditions that maximized the formation of the di-PFB ester
      (at the expense of the mono-PFB ester) of the dioic acids. After drying by
      evaporation, each sample residue was reconstituted in mesitylene and injected
      into a capillary GC-MS system via a splitless injection. The detection was by
      negative ion chemical ionization mass spectrometry with selected ion monitoring
      (SIM) of the [M-PFB]- of the analytes and the internal standard.

PMID- 9657221
TI  - Use of generic fast gradient liquid chromatography-tandem mass spectroscopy in
      quantitative bioanalysis.
AB  - Short narrow analytical HPLC columns have been used successfully with high linear
      flow-rates and combined with mass spectrometric detection to produce a generic
      approach to quantitative bioanalysis. The approach has been used to validate
      several assays in the low ng/ml region and an example is given in this paper.
      When combined with a simple solid-phase extraction process the need for
      complicated, time consuming method development has been removed for the majority
      of pharmaceutical compounds. The approach takes advantage of not only the extra
      selectivity of the MS-MS detector but the excellent resolution and peak shape
      produced by gradient elution.

PMID- 9657222
TI  - Quantitation of psilocin in human plasma by high-performance liquid
      chromatography and electrochemical detection: comparison of liquid-liquid
      extraction with automated on-line solid-phase extraction.
AB  - Two modifications of the HPLC-ED method with respect to extraction procedure used
      have been developed for psilocin, the active metabolite of psilocybin, in human
      plasma using either liquid-liquid extraction (LLE) or automated on-line solid
      phase extraction (on-line SPE). Each type of the sample preparation required a
      different HPLC system followed by electrochemical detection at 650 to 675 mV. The
      limit of quantitation of both modifications was 10 ng/ml psilocin. There was no
      significant difference observable between the LLE and the on-line SPE in terms of
      method standard deviation (LLE 1.82%, on-line SPE 1.13%) and the analytical
      results. However, the advantages of on-line SPE in addition to different
      selectivity were less manual effort, smaller plasma volumes of 400 microl (LLE 2
      ml) and a recovery of psilocin in human plasma of nearly 100% (LLE 88%). In
      contrast to a previous procedure both methods were rapid, simple and reliable and
      yielded high plasma recoveries. They were used successfully in the quantitation
      of psilocin in plasma samples obtained from healthy volunteers after p.o.
      administration of 0.2 mg psilocybin per kg body mass. Plasma concentration curves
      and pharmacokinetic parameters were calculated.

PMID- 9657223
TI  - Achiral and chiral high-performance liquid chromatographic methods for
      clinafloxacin, a fluoroquinolone antibacterial, in human plasma.
AB  - Achiral and chiral HPLC methods were developed for clinafloxacin, a quinolone
      antimicrobial agent. For achiral assay, analytes were isolated from plasma by
      precipitating plasma proteins. Separation was achieved on a C18 column using an
      isocratic eluent of ion pairing solution-acetonitrile (80:20, v/v) at 1.0 ml/min
      with UV detection at 340 nm. The ion pairing solution was 0.05 M citric acid,
      1.15 mM tetrabutylammonium hydroxide and 0.1% ammonium perchlorate. Inter-assay
      accuracy was within 4.9% with an inter-assay precision of 3.7% over a
      quantitation range of 0.025 to 10.0 microg/ml. For chiral assay, analytes were
      isolated from plasma by solid-phase extraction. Separation was achieved on a
      Crownpak CR(+) column using an isocratic eluent of water-methanol (88:12, v/v)
      containing 0.1 mM decylamine at 1.0 ml/min with UV detection at 340 nm.
      Perchloric acid was added to adjust pH to 2. Inter-assay accuracy was within 3.5%
      with a inter-assay precision of 5.4% over a quantitation range of 0.040 to 2.5
      microg/ml.

PMID- 9657224
TI  - Simultaneous determination of albendazole sulfoxide enantiomers and albendazole
      sulfone in plasma.
AB  - A high-performance liquid chromatographic method has been developed for the
      simultaneous determination of albendazole sulfoxide (ABZSO) enantiomers and
      albendazole sulfone (ABZSO2) in human plasma. The resolution of ABZSO enantiomers
      and ABZSO2 was obtained on a Chiralpak AD column using hexane-isopropanol-ethanol
      (81:14.25:4.75, v/v/v) as the mobile phase. The drugs were detected by
      fluorescence (lambda(exc) = 280 nm, lambda(em) = 320 nm). The drugs were
      extracted from 500 microl plasma with ethyl acetate, and after solvent
      evaporation, the residues were dissolved in the mobile phase and chromatographed.
      The method was precise and accurate for the three compounds, as judged by the
      coefficients of variation and relative errors observed. Linear standard curves
      were obtained in the concentration range of 5-2500 ng/ml for ABZSO enantiomers
      and 1-500 ng/ml for ABZSO2. A typical plasma concentration-time profile is
      presented for one patient under treatment for neurocysticercosis.

PMID- 9657225
TI  - Assay of paclitaxel (Taxol) in plasma and urine by high-performance liquid
      chromatography.
AB  - A new, rapid and sensitive high-performance liquid chromatographic method for the
      analysis of paclitaxel (Taxol) in human plasma and urine was developed and
      validated. After addition of an internal standard, paclitaxel was extracted from
      plasma or urine by a liquid-liquid extraction using diethyl ether. Extraction
      efficiency averaged 90%. Chromatography was performed isocratically on a reversed
      phase column monitored at 227 nm. Retention times were 7.7 and 6.7 min for
      paclitaxel and docetaxel, respectively, and the assay was linear in the range 25
      1000 ng/ml. The limits of quantification for paclitaxel were 25 and 40 ng/ml in
      plasma and urine, respectively. The assay was shown to be suitable for
      pharmacokinetic studies of children involved in a phase I clinical trial.

PMID- 9657226
TI  - Simultaneous high-performance liquid chromatographic determination of a
      glucuronyl prodrug of doxorubicin, doxorubicin and its metabolites in human lung
      tissue.
AB  - A rapid and sensitive method was developed for the simultaneous determination of
      the new doxorubicin glucuronide prodrug HMR 1826, the parent drug doxorubicin and
      its metabolites in human lung tissue samples. Homogenization of frozen tissue
      samples with the micro-dismembrator was followed by a silver nitrate
      precipitation step. By removing the exceeding silver ions with sodium chloride
      further purification steps could be omitted. Compounds were separated by
      isocratic high-performance liquid chromatography on a LiChrospher 100 RP18 column
      and a mobile phase consisting of citric acid buffer-acetonitrile-methanol
      tetrahydrofuran within 30 min and quantified with fluorescence detection. The
      method showed good recoveries for all compounds (86-99%) and a linear calibration
      range of 20 ng/g-80 microg/g for doxorubicin and 1-600 microg/g for HMR 1826.

PMID- 9657227
TI  - Determination of polyamines in human prostate by high-performance liquid
      chromatography with fluorescence detection.
AB  - A high-performance liquid chromatographic method for the determination of
      polyamines in human prostate has been developed. This method is based on pre
      column derivatization with dansyl chloride (Dns-Cl). The derivatives were
      separated on a muBondapak C18 column (250x4.6 mm I.D.; 10 microm), and eluted
      with methanol and distilled water using a one-step linear gradient. The column
      eluate was monitored by fluorescence detection (excitation, 370 nm; emission, 506
      nm). The within-assay precision of the study (C.V.) was as follows: putrescine
      (PUT) 2.88%, spermidine (SPD) 2.94% and spermine (SP) 1.17%. The between-assay
      precision (C.V.) was: PUT 2.66%, SPD 3.06%, SP 2.79%. The recovery was greater
      than 97%. The detection limit for PUT, SPD and SP were 0.05, 0.08 and 0.06
      nmol/ml, respectively. In contrast to other studies, sample or polyamine
      derivatives did not require extraction with an organic solvent such as ethanol,
      evaporation under vacuum or other condensation procedures. This is a simple,
      rapid and sensitive method that can be applied to the determination of polyamines
      in nearly all biological tissues and body fluids, such as urine and serum.

PMID- 9657228
TI  - One-step purification of proteins from chicken egg white using counter-current
      chromatography.
AB  - Proteins present in chicken egg white are separated by counter-current
      chromatography (CCC) in one step using a cross-axis coil planet centrifuge (X
      axis CPC). The separation was performed with an aqueous polymer two-phase system
      composed of 16% (w/w) poly(ethylene glycol) 1000 and 12.5% (w/w) dibasic
      potassium phosphate by eluting the lower phase at a flow-rate of 1.0 ml/min. From
      about 20 g of the crude egg white solution, lysozyme, ovalbumin, and
      ovotransferrin were resolved within 5.5 h. Each component was identified by 12%
      SDS gel electrophoresis with Coomassie brilliant blue staining.

PMID- 9657229
TI  - In situ evaluation of esterase stereoselectivity in two-dimensional
      electropherograms and tissue sections.
AB  - Staining with both enantiomers of an alpha-naphthyl ester plus a diazonium salt
      and comparing the color intensities given by the two enantiomers is a convenient
      method to evaluate the esterase stereoselectivity for that ester in two
      dimensional electropherograms and tissue sections. Application of this method for
      rat liver has shown that (1) several esterases, e.g., one of pI 6.4 and Mr 118
      kDa, are moderately stereoselective against alpha-naphthyl (R)-N-acetylalaninate
      and (R)-N-methoxycarbonylalaninate but strictly stereoselective against alpha
      naphthyl (S)-N-methoxycarbonylvalinate, implying that esterase stereoselectivity
      may be inverted by changing the ester structure; and (2) these esterases are
      mainly contained in the hepatocytes around central veins.

PMID- 9657230
TI  - Determination of indomethacin residues in poultry by high-performance liquid
      chromatography.
AB  - A HPLC method using a C18 column and UV detection (254 nm) is described for the
      determination of indomethacin residues in chicken tissues (liver, muscle and
      fat). Drug extraction from tissue homogenate in phosphate buffer (pH 3.5) was
      performed with dichloromethane. Mobile phase was acetonitrile-acetic acid (0.5%
      in water) (50:50). Indomethacin detection limit was 20 ng/g for the studied
      tissues. After administration of an oral dose of indomethacin (2 mg/kg), only
      three of the eight poultry studied showed drug tissue levels, in those cases the
      levels were below 50 ng/g.

PMID- 9657231
TI  - Improved high-performance liquid chromatographic analysis of teniposide in human
      plasma.
AB  - A simple and practical high-performance liquid chromatographic analysis has been
      developed for measuring teniposide (VM26) in human plasma. The present analytical
      method has improved extraction efficiency from human plasma, therefore allowing
      determination of VM26 in a clinical setting using ultraviolet detection alone.
      Furthermore, sample preparation was simplified and shortened through use of a one
      step extraction procedure. VM26 and internal standard (ibuprofen) were extracted
      from human plasma (0.5 ml) with ethyl acetate. A phenyl muBondapak column eluted
      with a mobile phase, consisting of acetonitrile-distilled water-acetic acid
      (30:68:2, v/v/v) was used for separation, and quantitation was achieved with a UV
      monitor set at 240 nm. Average extraction efficiency was 96.8+/-6.6% for VM26
      between 1 and 25 microg/ml, and 91.4+/-4.3% for internal standard, with both
      intra- and inter-day coefficients of variation being less than 10%. The detection
      limit with a 100-microl injection was estimated at 0.2 microg/ml with a signal-to
      noise ratio of 3 for VM26 in human plasma. The stability data of VM26 in plasma,
      standard and stock solutions were also obtained. The present method was found to
      be an alternative to the previously reported method with an electrochemical
      detection, and can be easily applied to routine clinical pharmacokinetic studies
      of VM26.

PMID- 9657232
TI  - Selection of internal standard for quantitative analysis of enantiomers following
      precolumn chiral derivatization.

PMID- 9657233
TI  - Borna or not?

PMID- 9657234
TI  - A viro-psycho-immunological disease-model of a subtype affective disorder.
AB  - Borna Disease Virus (BDV) infections are widespread in animal species. This
      neurotropic, negative and single-stranded enveloped RNA virus spreads via axonal
      and transsynaptic pathways quite specifically into olfactoric and limbic
      structures. The symptoms in BDV-infected animals range from unapparent or subtle
      clinical manifestations to fatal neurological disorders. The severe and fulminant
      course of the infection, which is often accompanied by neurobehavioral and
      "emotional" disturbances, occurs sporadically and, at least in experimentally
      infected animals (rats), is thought to be mediated by immunopathology. Increases
      in serum-BDV antibodies have also been detected in neuropsychiatric patients. In
      addition, viral antigen and viral RNA have been observed in acutely ill major
      depressive patients, leading to the conclusion that BDV was causally related to
      psychiatric disorders, in particular to affective disorders. A number of studies
      have meanwhile furnished evidence of abnormal immune functions in mentally ill
      patients. In addition, stress has been shown to decrease immune responses to
      viral infections. On the basis of these findings it is hypothesized that human
      BDV infection represents a co-factor in the development or course of psychiatric
      diseases. Stress may cause immunosuppression and thus induce activation of
      persisting BDV in the limbic system, resulting in an inflammatory reaction of
      these structures. These neuropathological changes might influence the
      serotonergic or dopaminergic neurotransmitter systems. In addition, a specific
      affinity of BDV structural elements for aspartate and glutamate receptors in the
      hippocampal formation might directly induce an imbalance of these transmitter
      system interactions, causing affective and behavioral disturbances. The possible
      interactions between stress-induced immunosuppression, BDV infection and
      affective disorders in humans, and the theoretical and clinical aspects of this
      concept are discussed.

PMID- 9657235
TI  - The symmetry of symptom patterns in pre-post treatment designs.
AB  - This article proposes a new nonparametric method for statistical evaluation of
      clinical pre-post treatment designs. In clinical research, models of marginal
      symmetry typically are estimated from log-linear models of axial and quasi
      symmetry. As such, they provide overall goodness-of-fit information concerning
      change in probabilities of categories of one variable that was observed twice.
      This paper proposes the following three extensions: (1) using models of marginal
      symmetry for changes in patterns of two or more variables, and (2) following up
      global marginal symmetry tests using Lehmacher's sign tests. (3) To protect the
      experiment-wise alpha, a modified Bonferroni-Holm procedure is proposed. The new
      approach allows researchers to make statements about treatment effects at the
      level of single symptoms. Examples illustrate application of all three symmetry
      models and the follow-up test using data from pharmaco-psychiatry. The discussion
      relates Lehmacher's tests to two-sample Configural Frequency Analysis of multi
      discrimination types. Strategies of statistical significance testing are
      presented and the importance of the proposed methodological approach for
      psychiatric research is discussed.

PMID- 9657236
TI  - Paroxetine: a review of clinical experience.
AB  - The selective serotonin reuptake inhibitor paroxetine has been extensively
      studied and is now an established therapy for the treatment of depressive
      disorders. Paroxetine has demonstrated efficacy in major depression in both young
      and elderly patients, with an improved tolerability profile over conventional
      antidepressants. Paroxetine is effective across a continuum of anxiety and
      depressive disorders, including severe depression, depression with anxiety,
      comorbid depression and obsessive-compulsive disorder. The first agent of its
      class licensed for use in panic disorder, paroxetine has been shown to be
      effective in reducing the number of panic attacks and preventing relapse. A
      worldwide clinical database has established that paroxetine has a benign adverse
      event profile. Paroxetine therefore offers an effective and well tolerated
      treatment for a broad spectrum of psychiatric disorders.

PMID- 9657237
TI  - Plasma concentrations of risperidone and its 9-hydroxy metabolite and their
      relationship to dose in schizophrenic patients: simultaneous determination by a
      high performance liquid chromatography with electrochemical detection.
AB  - A simple, sensitive and accurate method for the simultaneous determination of
      risperidone (RSP) and its 9-hydroxy metabolite (9-OH-RSP) in human plasma is
      described. The relationship between dose of RSP and the plasma concentration of
      RSP and 9-OH-RSP in a clinical situation is discussed. Both compounds were
      isolated from plasma by a simple one-step liquid-liquid extraction with 15%
      methylene chloride in pentane. High-performance liquid chromatography separations
      were made on a cyano column and the compounds were detected by electrochemical
      detector. The method had sufficient sensitivity to determine RSP and 9-OH-RSP
      accurately at concentrations as low as 0.25 ng/ml when 1 ml of plasma is used for
      the analysis. The assay determinations were accurate, precise and consistent with
      a coefficient of variation less than 15%. Commonly co-administered drugs and
      other antipsychotics did not interfere with the analysis of either RSP or 9-OH
      RSP There were large variations in inter- and intra-individual values of plasma
      concentrations of RSP and 9-OH-RSP. The 9-OH-RSP appears to be the major
      circulating active moiety and its plasma concentrations were, on the average 22
      fold higher than that of RSP in schizophrenic patients treated with RSP. The
      ratio of RSP/9-OH-RSP concentrations suggested that three of the patients may
      have deficiency in cytochrome P450 enzyme CYP 2D6. The plasma concentrations of
      RSP showed a weak relationship with the administered daily oral dose (r = 0.4684,
      p = 0.01, n = 215). However, there was a good relationship between the daily dose
      of RSP and the plasma concentration of 9-OH-RSP (r = 0.6654, p = 0.01, n = 280)
      or the total active moiety, sum of RSP and 9-OH-RSP concentrations (r = 0.7041, p
      = 0.0005, n = 280). The measurement of the total active moiety in plasma of
      schizophrenic patients may be useful for assessing the relationship between dose
      and plasma concentration and dose and clinical outcome of patients rather than
      measuring RSP alone.

PMID- 9657238
TI  - Lack of psychotomimetic or impairing effects on psychomotor performance of
      acamprosate.
AB  - The possible effects on psychomotor performance, concentration, attention, and
      mood of acamprosate (calciumacetylhomotaurinate) were assessed using a
      randomized, double-blind, cross-over, placebo-controlled design involving 12
      healthy male volunteers. Acamprosate 2 g daily per os or placebo was administered
      for seven days and separated by washout intervals of at least 21 days. Objective
      tests evaluated psychomotor functions (simple reaction time measurement, binary
      choice reaction test, computerized visual searching task, sustained attention
      test). Mood was assessed using the Beck Depression Inventory and the Beschwerde
      Liste to assess subjective physical impairment. Additionally, a visual 3-D
      illusion paradigm was applied to measure the psychotomimetic effect. A dose of
      acamprosate of 2 g/day for seven days was free of any significant effects on
      mood, concentration, attention, psychomotor performance and did not produce any
      subjective sedation, excitation or psychotomimetic effects.

PMID- 9657239
TI  - Gastrointestinal side-effects after switch to generic valproic acid.

PMID- 9657240
TI  - Abdominal Takayasu's aortitis, the middle aortic syndrome and atherosclerosis. A
      critical review.
AB  - To review the current status of clinical, pathological and arteriographic aspects
      of abdominal Takayasu's aortitis (TA). Personal experience with 86 patients with
      TA and review of the literature is the basis of this report. The diagnostic
      significance of primary versus secondary atherosclerosis is described in this
      communication and the arteriographic differential diagnostic guidelines are
      provided to separate abdominal TA from abdominal atherosclerosis.

PMID- 9657241
TI  - Intraoperative assessment of cerebral ischaemia during carotid surgery.
AB  - BACKGROUND: This study aimed to evaluate the reliability of somatosensory evoked
      potentials (SEPs) in identifying clamping ischaemia during carotid surgery under
      general anaesthesia. METHODS: We reviewed the records of 196 consecutive carotid
      endarterectomies (CEA) performed under general anaesthesia, out of 1550 patients
      operated on between 1975 and 1993. SEPs were monitored after contralateral median
      nerve stimulation at the wrist in all patients. Moreover they received an
      intravenous bolus of 2500 IU of heparin and the stump pressure was measured. A
      completion angiography was performed in all patients. An intraluminal shunt was
      inserted when the amplitude of the N20-P25 SEPs complex decreased by more than
      50% of pre-clamping value (pathologic SEPs) or when a preoperative CT-scan showed
      an ischaemic area in the contralateral hemisphere. In some patients the shunt was
      not inserted because of technical difficulties or because the pathological SEP
      complex decrease developed when the suture of the arteriotomy was almost
      complete. RESULTS AND CONCLUSIONS: As the preclamping amplitude (Ab) of N20-P25
      was extremely variable, ranging from 0.9 and 7.5 microV, we adopted the ratio:
      deltaA=(At-Ab)/Ab (At=amplitude measured during clamping every 2 min at time t).
      Mean decrease of deltaA measured in the whole group ranged between 15% and 20%,
      but mean deltaA values in patients with pathological SEPs were around 60%. Even
      patients with positive CT-scans or with a back-pressure lower than 50 mmHg
      developed a mean deltaA decrease of about 20%. A pathological SEP was present in
      50 patients, but developed in only 12 during the clamping trial. An intraluminal
      shunt was inserted in 22 cases; the other patients received pharmacological
      treatment with anaesthetic or vasoactive drugs. Among the patients with
      pathological SEPs, 3 presented postoperative symptoms related to carotid cross
      clamping; only 1 of these was shunted but without SEPs normalisation. No patients
      with normal SEPs developed a postoperative neurological deficit, giving a
      reliability of 86.7%, a sensitivity of 100% and a specificity of 86.5%.

PMID- 9657242
TI  - Carotid atherosclerosis in subjects with different hyperlipidaemia phenotypes.
AB  - OBJECTIVE: To evaluate the presence of carotid plaque and/or stenosis in patients
      with different phenotype of hyperlipidaemia. EXPERIMENTAL DESIGN: Case-control
      study. SETTING: Outpatients metabolic clinic. PATIENTS: Sixty type IIa, 50 type
      IIb and 40 type IV hyperlipidaemic subjects were compared with 50 normolipidaemic
      controls, matched for sex and age. INTERVENTIONS: Blood lipid analysis for
      phenotype classification was performed after two months of diet. Blood pressure
      was measured by a zero-random sphygmomanometer. CHD risk factors, smoking habit,
      previous and ongoing drug therapy were assessed by a self-administered
      questionnaire. Echo-Doppler examination of the extracranial arteries (common,
      internal and external carotid artery and bulb) was done by a Multigon Angioview
      600 provided with a 7.5 MHz probe for B-mode and 5 MHz for pulsed Doppler.
      Subjects were classified as having carotid atherosclerosis when a plaque and/or a
      stenosis was found in at least one of the examined segments and as normal when no
      atherosclerotic lesions were detected. RESULTS: There were more hypertensives
      among type IV subjects whereas the prevalence of smokers and diabetics was
      similar in all four groups. The prevalence of carotid atherosclerosis was higher
      in type IIb and IIa subjects than in controls (58% and 38% respectively vs 14%,
      p<0.01) while in type IV subjects it was comparable to that of controls (25%).
      CONCLUSIONS: The present findings show that hypercholesterolaemia and mixed
      hyperlipidaemia are frequently associated with carotid atherosclerosis, whereas
      hypertriglyceridaemia is not. The role of hypertriglyceridaemia in the
      development of atherosclerosis seems mediated by mechanisms other than plaque
      formation.

PMID- 9657243
TI  - Prevalence of morphological alterations in cervical vessels: a colour duplex
      ultrasonographic study in a series of 3300 subjects.
AB  - BACKGROUND: In order to define the morphological variants involved in carotid
      elongation in terms of their clinical implications, we have analysed the
      prevalence of morphological alterations in patients routinely subjected to
      carotid colour duplex ultrasonography evaluation. METHODS: From January 1, 1993
      to June 30, 1996, 3300 subjects were examined for central nervous system symptoms
      (41% of cases) or for screening related to ischaemic heart disease, lower limb
      arterial disease, hypertension or major dyslipidaemia (59% of cases). The chi(2)
      test was used for statistical analysis. RESULTS: Morphological alterations
      increased with age. While kinking was more prevalent in females (female:male
      ratio 58% vs 42%), sharp kinking was significantly more frequent in males (39% vs
      15%, p<0.001). Atheromatous plaques predominated in males (79% vs 46%, p<0.001),
      as well as cases with haemodynamically significant involvement (16% vs 7%,
      p<0.001). In patients with kinking there was a prevalence of haemodynamically
      significant lesions (chi(2)=52.7, p<0.001). A possible link between
      conformational abnormalities and hypertension appeared highly significant owing
      to a very different prevalence of high blood pressure in the group of subjects
      with kinking (chi(2)=239, p<0.001). We did not find a significant association
      between major neurological symptoms and the presence of kinking (chi(2)=0.215,
      p=0.643), but we found an association with transient ischaemic attacks
      (chi(2)=6.9, p<0.01). CONCLUSIONS: Conformational abnormalities like kinking,
      seem much more prevalent in subjects suffering from arterial hypertension. Even
      though high blood pressure is an important risk factor for transient ischaemic
      attacks, it is possible that the prevalence of atheromatous lesions and the flow
      turbulence linked to kinking may also play a role in their pathophysiology.

PMID- 9657244
TI  - Outcome after early treatment of popliteal artery aneurysms.
AB  - BACKGROUND: Aneurysms of the popliteal artery are rare events with an estimated
      incidence of 0.1-2.8%. Their clinical importance depends on their propensity to
      cause thromboembolic complications or to rupture (18 to 31% of cases). This study
      was designed to assess the advantages of elective treatment of asymptomatic
      popliteal artery aneurysms so as to avoid the severe clinical manifestations that
      eventually arise if they remain untreated. METHODS: From 1980 to 1995, in our
      department we treated 28 popliteal aneurysms in 23 patients (19 elective
      operations and 6 emergencies). Three of the aneurysms proved amenable to
      fibrinolytic therapy alone. Follow-up lasted a mean 48 months (range 3 months to
      15 years) in 20 patients (23 revascularizations). RESULTS: Global patency was
      91.3%. Two thrombosed bypasses were treated by thrombolysis; in one case it did
      not resolve the ischaemia and the leg was amputated. In one case only, a graft
      became infected but this responded to conservative therapy with drainage and
      antibiotics. CONCLUSIONS: These findings suggest that popliteal aneurysms with
      good distal run-off should be repaired electively. Completely thrombosed
      aneurysms with coexistent limb-threatening ischaemia should be treated initially
      by thrombolysis. This will usually restore run-off and in some cases offers a
      valid alternative to emergency surgery for limb salvage.

PMID- 9657245
TI  - Factor G pathway reactive activity (GPRA) after surgery for abdominal aortic
      aneurysm.
AB  - BACKGROUND: Following major surgery, detection of endotoxaemia using the
      Toxicolor (Limulus) test has been reported. In addition to endotoxins, this test
      detects a reactant from human tissue, factor G pathway reactive activity (GPRA).
      We measured endotoxin and GPRA in 10 patients during and after elective surgery
      for abdominal aortic aneurysm. Additionally, we measured phosphokinase (CPK) and
      GPRA levels in the muscle of 10 patients during abdominal aortic aneurysm surgery
      and 6 during open laparotomy for other causes. METHODS: Samples were taken from
      the arterial lines prior to surgery, before cross-clamping of the aorta,
      immediately after and 1, 3, 6, and 18 hours after declamping. Muscle specimens
      were taken from the rectus abdominus and homogenized in many levels. Endotoxin
      concentrations were measured with the Endotoxin-Specific test. GPRA
      concentrations were determined by subtracting the values from the Endotoxin
      Specific test from those given by the Toxicolor test (Limulus assay with
      achromogenic substrate). CPK was also measured. RESULTS: Endotoxin did not
      significantly increase during or after surgery, but GPRA was elevated. GPRA in
      muscle correlated significantly with CPK in muscle. CONCLUSIONS: We conclude that
      GPRA was elevated after surgery, while endotoxin did not increase significantly.
      The GPRA probably originated from human muscle tissue.

PMID- 9657246
TI  - Decrease of platelet intracellular pH and adhesion by ticlopidine in patients
      with vascular disease.
AB  - BACKGROUND: Ticlopidine inhibits platelet aggregation by preventing the binding
      of fibrinogen to its platelet receptor. We examined whether this inhibition
      involved platelet transduction system such as Na+/H+ pump and platelet
      intracellular calcium. METHODS: Platelet adhesion in 13 patients with peripheral
      vascular disease treated with ticlopidine, 250 mg b.i.d for 30 days, was measured
      in culture microplates before and after therapy. The microplate wells were coated
      with human plasma, fibrinogen or collagen, and platelet adhesion was studied in
      the resting condition and after stimulation with 1 and 10 microM ADP. At the same
      time, platelet intracellular calcium and ADP-induced calcium increases were
      measured with the fluorescent indicator Fura 2. In addition, intracellular pH and
      thrombin-induced pH variations were measured with the fluorescent probe BCECF.
      RESULTS: Platelet adhesion to plasma and fibrinogen was significantly reduced
      (about 50%) after treatment with ticlopidine, while adhesion to collagen was not
      modified. Basal calcium and ADP-induced calcium increase were not significantly
      different before and after ticlopidine. Platelet basal intracellular pH was
      reduced (from 7.44+/-0.009 to 7.41+/-0.017, p<0.05), but agonist-induced
      alkalinisation was not significantly different. Early acidification, not
      dependent on Na+/H+ exchange, was also reduced (p<0.05). CONCLUSIONS: These data
      do not seem to support the hypothesis that ticlopidine-induced reduction of
      platelet adhesion depends on alteration of the mechanisms determining signal
      transduction, at least as far as basal and post-stimulation intracellular calcium
      is concerned. On the contrary, the possibility that ticlopidine inhibits the
      Na+/H+ antiport remains open to consideration.

PMID- 9657247
TI  - Power-based colour coded duplex sonography for evaluation of calf veins.
AB  - BACKGROUND: Power-based colour coded duplex sonography (PD) has been described to
      display lower flow velocities compared to frequency-based colour coded duplex
      sonography (CD). This study was undertaken to study the clinical usefulness of PD
      in the evaluation of calf veins in suspected deep vein thrombosis. METHODS: 
      EXPERIMENTAL DESIGN: A prospective, comparative study. SETTING: University
      hospital, Switzerland. PATIENTS AND MEASURES: CD of the complete deep venous
      system and complementary PD of paired calf veins were performed in 50 consecutive
      patients with clinically suspected DVT. All except three patients, with failed
      vein puncture at the dorsum of the foot, had a venography used as reference test
      for confirmatory diagnosis of DVT. RESULTS: Complete identification of calf veins
      increased from 80.5% using CD to 97.9% using complementary PD (p=0.007). Overall
      accuracy to detect an acute calf DVT was 96% (95% Ci, 85-99%) and 95% (95% CI, 83
      99%), respectively. Accuracy was 95% (95% CI, 83-99%) using CD vs 94% (95% CI, 82
      98%) using PD in posterior tibial, 87% (95% CI, 74-95%) vs 85% (95% CI, 71-94%)
      in anterior tibial, and 95% (95% CI, 83-99%) vs 96% (95% CI, 85-99%) in peroneal
      veins. Chronic post-thrombotic changes (10.6%) were more reliably recognized
      using CD (accuracy 83% [95% CI, 72-94%]) compared to PD (accuracy 66% [95% CI, 59
      85%]) due to tissue motion artifacts and inability to discriminate the direction
      of blood flow. CONCLUSIONS: PD used complementary with CD is capable of
      significantly improving identification of paired calf veins without loss of
      diagnostic accuracy in the diagnosis of acute DVT.

PMID- 9657248
TI  - Levels of the inhibitor of PMN-elastase in venous blood reflowing from
      chronically affected veins: the role of venous stasis.
AB  - BACKGROUND: Attention has recently been paid to the cell and biochemical
      disorders involved in chronic venous insufficiency (CVI) and to their possible
      relationship to the endothelium. METHODS: In the present study, carried out in 14
      patients with CVI, we evaluated the levels of the inhibitor of elastase (I-EL)
      generated by polymorphonucleate cells in the blood reflowing from affected
      superficial veins of legs both at rest and after prolonged venous stasis (1 hour
      in standing position). RESULTS: We evaluated the I-EL both as percentage of
      activity (baseline 82.3+/-24.5%; after stasis 100.7+/-37.8%) and as absolute
      values (0.67+/-0.26 U/ml; after stasis 0.79+/-0.39 U/ml). In blood samples taken
      after venous stasis we found a tendency toward a trapping of white blood cells
      and an increase of the haematocrit over baseline. The difference in the
      percentages of activity of I-EL was statistically significant, but only a trend
      was observed for the absolute values. CONCLUSIONS: We believe that the typical
      haemodynamic disorders of patient with CVI increased by prolonged venous stasis
      can modify the function of white blood cells, which are closely linked with
      venous hypertension, thus playing an important role in the pathogenesis of skin
      ulcers.

PMID- 9657249
TI  - Importance of cutaneous postural reflex vasoconstriction in patients with
      atherosclerotic occlusive disease of the lower extremities.
AB  - OBJECTIVE: The present study was designed to measure the cutaneous postural
      vasoconstrictive reflex (PVR) in normal controls and patients with
      atherosclerotic occlusive disease of the lower extremities, and to determine its
      diagnostic and prognostic relevance. EXPERIMENTAL DESIGN: The postural
      vasoconstrictive reflex was recorded in 34 patients with atherosclerotic
      occlusive disease of the lower limbs and 27 normal controls, using laser-Doppler
      flowmetry. Patients also had ankle and toe pressure measurements and
      transcutaneous oximetry (TcPO2). SETTING: University hospital. RESULTS: The PVR
      on the pulp of the big toe was 20+/-7 arbitrary perfusion units in normal
      controls, 9.4+/-12 in patients with claudication, and -19 +/- 5 in patients with
      rest pain and/or gangrene, who differed from the claudicant and control groups
      (p=0.001 and 0.0001 respectively). The sensitivity of negative PVR in the big toe
      was 89% for the diagnosis of rest pain and/or gangrene, and its specificity, 83%.
      The severity of foot ischaemia and PVR values exhibited a significant inverse
      correlation (r=-0.56, p<0.0001). All patients with a poor outcome, ie. death
      and/or major amputation within 100 days of follow-up, had a negative PVR, and all
      patients with a positive PVR had a good 100-day prognosis without even a minor
      amputation. CONCLUSIONS: Laser-Doppler provides useful additional information in
      the assessment of foot ischaemia severity by showing that postural
      vasoconstriction is impaired in patients with severe atherosclerotic occlusive
      disease of the lower limbs, resulting in increased skin microcirculatory flow
      during leg dependency.

PMID- 9657250
TI  - Hyperselective renal artery embolisation in the treatment of post-traumatic
      iatrogenic haematuria: report of two cases.
AB  - Angiography and selective renal artery embolisation were performed in two
      patients with post-traumatic iatrogenic kidney lesions and intractable
      haematuria. One patient presented after a nephrolithotomy with rupture of a
      segmental branch of the renal artery well demonstrated on selective angiography
      which showed intraparenchymal extravasion of contrast medium. The other presented
      after a renal biopsy with severe haematuria. Angiography performed 10 days later
      demonstrated an arteriovenous fistula at the site of the puncture. Hyperselective
      embolisation achieved immediate control of the haematuria in both patients, with
      maximal preservation of the renal parenchyma and maintenance of good renal
      function. At follow-up 12 months later, there had been no recurrence of the
      haematuria. These results suggest that transcatheter embolisation should be
      considered the method of first choice in renal trauma accompanied by intractable
      haematuria before any surgery is attempted.

PMID- 9657251
TI  - Anplag, a selective 5-HT2 receptor antagonist, reduces stenosis induced by
      balloon injury in hypercholesterolaemic rabbit.

PMID- 9657252
TI  - The inflammatory basis of trauma/shock-associated multiple organ failure.
AB  - Multiple alterations in inflammatory and immunologic function have been
      demonstrated in clinical and experimental situations after trauma and hemorrhage,
      in particular the activation of various humoral (e.g. complement, coagulation)
      and cellular systems (neutrophils, endothelial cells, macrophages). As a
      consequence of this activation process there is synthesis, expression and release
      of numerous mediators (toxic oxygen species, proteolytic enzymes, adherence
      molecules, cytokines), which may produce a generalized inflammation and tissue
      damage in the body. Mediators are responsible for ongoing interactions of
      different cell types and for amplification effects through their networks and
      feedback cycles, finally leading to a sustained inflammation and multiple organ
      damage in the body. In the setting of trauma/shock, many activators including
      bacterial as well as non-bacterial factors may be present that will induce local
      and systemic inflammatory responses. Although the potential role of
      bacteria/endotoxin translocation and its clinical relevance remains
      controversial, many lines of evidence support the concept that the gut may be the
      reservoir for systemic sepsis and subsequent MOF in a number of pathophysiologic
      states.

PMID- 9657253
TI  - The role of histamine in platelet aggregation by physiological and immunological
      stimuli.
AB  - BACKGROUND: Platelets participate in allergic and inflammatory processes beside
      their role in haemostasis and thrombosis. This paper reports the level, the
      uptake, the metabolism and the release of histamine in human platelets. The
      effects of exogenous histamine, as well as the receptor and signal transduction
      of these effects, are also described. METHODS: Purified suspensions of platelets,
      prepared from healthy volunteers and from atopic patients, were exposed in vitro
      to physiological and immunological stimuli. Platelet aggregation was measured by
      the increase in light transmission; histamine content and release, as well as
      cytosolic free Ca2+ concentration, were measured fluorimetrically. Platelet
      histamine forming capacity, and the uptake of exogenous histamine, were measured
      with a radioisotopic method. RESULTS: Human platelets contain 72.5 +/- 9.6pmoles
      of histamine x 10(9) platelets, and their capacity to form histamine is 18.7 +/-
      3.5pmoles h(-1)g(-1) protein, which is reduced by alpha-fluoromethylhistidine
      (10(-5) M) a selective inhibitor of the specific histidine decarboxylase. Human
      platelets take up the preformed amine by a calcium and energy-dependent process,
      and the uptake of histamine is reduced by mepyramine, an H1-receptor antagonist,
      and N,N-diethyl-2-[4-(phenylmethyl) phenoxyl] ethanamine (10(-6) M), a blocker of
      intracellular histamine receptors. Histamine is also metabolized by human
      platelets. The exposure of platelets to thrombin (10-60 mUml(-1)) produced a
      progressive aggregation, associated with histamine release. The same is observed
      in platelets isolated from atopic patients exposed to anti-IgE antibodies.
      Exogenous histamine dose-dependently potentiates the aggregation induced by
      physiological and immunological stimuli. In resting platelets cytosolic calcium
      level (207 +/- 4.2 nM/10(8) platelets) is increased by thrombin as well as by
      anti-IgE; this effect is potentiated by 10(-5) M histamine. CONCLUSIONS: The
      synergistic effect between histamine and other monoamines on platelet aggregation
      may explain some aspects of allergic vasculitis in which platelet aggregation is
      present.

PMID- 9657254
TI  - Regulation of interleukin-6, and macrophage colony-stimulating factor mRNA levels
      by histamine in stromal cell line (MC3T3-G2/PA6).
AB  - OBJECTIVE: The aim of this study was to examine the role of histamine in
      regulation of IL-6 and M-CSF gene expression in bone marrow stromal cells. Total
      cellular synthesis was also estimated for IL-6. MATERIALS: The effects of the
      amine were evaluated using the stromal cell line, MC3T3-G2/PA6 (PA6). RESULTS:
      Histamine caused a distinct accumulation of IL-6 mRNA in the cells, whereas it
      decreased M-CSF transcripts. Both pyridylethylamine, a H1 agonist, and dimaprit,
      a H2 agonist, caused a large increase in the level of IL-6 mRNA in PA6 cells. The
      histamine-induced expression of IL-6 mRNA was associated with enhanced secretion
      of IL-6, as determined by ELISA. CONCLUSIONS: These results, together with the
      results of our previous studies, suggest that histamine produced by stromal
      macrophages differentially regulates the production of IL-6 and M-CSF in other
      kinds of stromal cells and hence promotes differentiation and/or proliferation of
      hematopoietic progenitor cells.

PMID- 9657255
TI  - Effects of the cyclooxygenase-2 inhibitor NS-398 on thromboxane and leukotriene
      synthesis in rat peritoneal cells.
AB  - OBJECTIVE: Inhibition of inducible cyclooxygenase (COX)-2 has been suggested to
      offer therapeutic advantages without some side effects associated with the
      inhibition of constitutive COX activity. These side effects encompass asthmatic
      responses that can be induced by analgesic/ antiphlogistic drugs and are possibly
      related to increased leukotriene (LT) biosynthesis. We have therefore
      investigated whether or not the selective COX-2 inhibitor NS-398, similar to
      indomethacin, stimulates leukotriene (LT) biosynthesis in rat peritoneal cells.
      METHODS: Three hours after rats had received intraperitoneal injections of
      bacterial lipopolysaccharide (LPS) or saline, cells were obtained by peritoneal
      lavage. Northern blot analysis confirmed induction of COX-2 mRNA by LPS
      treatment. For determination of eicosanoid biosynthesis, peritoneal cells were
      incubated in the presence of various concentrations of test compounds for 60 min.
      The supernatants were used for radioimmunological determination of immunoreactive
      eicosanoids. RESULTS: In cells from LPS treated rats, but not in controls, NS-398
      (10-300nM) reduced the amount of TXB2-like immunoreactivity (IR) in the
      supernatants, the maximum effect being a 25% inhibition. At these concentrations,
      there was no detectable effect of NS-398 on the amount of LTB4-IR or LTC4-IR in
      the supernatants. At higher concentrations (1-10 microM), NS-398 caused further
      inhibition of TXB2 synthesis, an effect that was observed also in non-LPS treated
      preparations. A significant increase of LTB4-IR was caused by 3-10 microM NS-398.
      Indomethacin (3-100 nM) reduced the amount of TXB2-IR, and at >10 nM increased
      the amount of LTB4- and LTC4-IR in the supernatant. CONCLUSIONS: The results show
      that concentrations of NS-398 that selectively inhibited COX-2 activity, produced
      no detectable increase in LT biosynthesis, thus raising the possibility that COX
      2 inhibitors are less likely than non-selective COX inhibitors to produce LT-
      related side effects.

PMID- 9657256
TI  - Bradykinin increases intracellular calcium levels in a human bronchial epithelial
      cell line via the B2 receptor subtype.
AB  - OBJECTIVE: To determine which types of kinin receptor are present in human
      bronchial epithelial cells we studied the capability of bradykinin to mobilize
      intracellular Ca2+ ([Ca2+]i) in a human bronchial epithelial cell line (16HBE
      cells). MATERIAL: Human bronchial epithelial cell line transformed with an
      original defective simian virus 40 (SV40). TREATMENT: Bradykinin (0.1 pM to 0.1
      microM), des-Arg9 bradykinin (1 microM), des-Arg10) kallidin (1 microM),
      indomethacin (1 microM), phosphoramidon (1 microM), captopril (1 microM), des
      Arg9-[Leu8]bradykinin (1 microM), HOE 140 (DArg-[Hyp3, Thi5, DTic , Oic8]
      bradykinin) (1 microM), and NPC 16731 (DArg-[Hyp3, Thi5, DTic7, Tic8]-bradykinin)
      (1 microM). METHODS: The mobilization of [Ca2+]i was determined by the fura-2
      method. Two sample Wilcoxon rank-sum (Mann-Whitney) test was used for statistical
      calculations. RESULTS: Bradykinin, but not the selective agonists for kinin B1
      receptor des-Arg9 bradykinin and des-Arg10 kallidin, increased the mobilization
      of [Ca2+]i (EC50, 0.079+/-0.009nM) in 16HBE cells in a concentration-dependent
      manner. Pretreatment with the cyclooxygenase inhibitor indomethacin (1 microM) or
      the peptidase inhibitors, phosphoramidon (1 microM) or captopril (1 microM), did
      not affect the response to bradykinin. The kinin B1 receptor antagonist, des-Arg9
      [Leu8]bradykinin (1 microM), was inactive. HOE 140 and NPC 16731, two selective
      antagonists of the kinin B2 receptor abolished the response to bradykinin (IC50
      of HOE 140 and NPC 16731 were 0.52+/-0.037nM and 1.67 +/- 0.41 nM, respectively).
      CONCLUSIONS: The present data indicate the presence of kinin B2 receptors in the
      16HBE cells.

PMID- 9657257
TI  - Surrogate thrombopoietin.
AB  - The extracellular domain of human c-Mpl, the receptor for thrombopoietin (TPO),
      was expressed as a chimeric protein with the interleukin-2 receptor alpha chain
      on the surface of murine B cell-line B300-19. BALB/c mice were immunized with
      cells expressing the chimeric protein. The IgG purified from the resulting immune
      serum immunoprecipitated human c-Mpl. The immune IgG supported proliferation of
      both stable transfectant Ba/F3 cells expressing whole c-Mpl molecules (c-Mpl
      Ba/F3 No. 9) and UT7/TPO cells bearing naturally occurring c-Mpl, whereas it did
      not support the growth of the untransfected parental Ba/F3 cells. Cell growth was
      induced using 3 to 100 microg/ml of immune IgG in a dose-dependent manner, but
      this induction was decreased at doses higher than 100 microg/ml. Non-immune IgG
      did not affect cell growth of c-Mpl-Ba/F3 No. 9 cells. Although the Fab fragment
      of immune IgG also immunoprecipitated c-Mpl, it did not support cell growth at
      concentrations as high as 180 microg/ml, implying that the bivalent binding of
      receptors by antibodies is essential for cell proliferation. These results
      suggest that antibodies against human c-Mpl stimulate the proliferation and
      differentiation of megakaryocytes by their bivalent binding to receptors like
      TPO.

PMID- 9657258
TI  - Effect of Pseudomonas aeruginosa exotoxin A on CD3-induced human T-cell
      activation.
AB  - The effect of Pseudomonas aeruginosa (PA) exotoxin A (P-ExA) on CD3-induced T
      cell activation was studied on the level of T-cells (proliferation, synthesis of
      interleukin (IL)-2, expression of IL-2R complex, ICAM-1,2 and LFA-1 molecules),
      and on the level of monocytes (expression of ICAM-1,2, LFA-1 molecules, as well
      as FcRI and CD14 receptors). We found that: (1) P-ExA blocked T-cell
      proliferation and this effect was totally reversed by intact monocytes, and
      partially by IL-2 or TPA but not by costimulatory cytokines (IL-1alpha, IL-1beta,
      TNF-alpha or IL-6); (2) P-ExA transiently, in short-term cultures (48 h),
      inhibited synthesis of IL-2; (3) prolonged stimulation (96 h) of peripheral blood
      mononuclear cells (PBMC) or CD4 + T-cells with P-ExA in high or low doses (100
      and 10 ng/ml, respectively), enhanced the level of IL-2 in the cultures; (4) P
      ExA at low dose, combined with IL-1beta, TNF-alpha or IL-6, up-regulated
      synthesis of IL-2; and (5) stimulation of T-cells with anti-CD3 monoclonal
      antibody (mAb) and P-ExA at high dose diminished the expression of the p55 chain
      but not of the p75 chain of IL-2R complex and slightly affected the expression of
      CD3 complex, ICAM-1,2 and LFA-1 molecules. Hence, P-ExA can regulate the level of
      IL-2 in cultures of CD3-induced T-cells either by inhibition of IL-2 consumption
      (when P-ExA is applied in high dose), or by induction of IL-2 production (a
      costimulatory effect exerted by P-ExA in low dose in combination with monokines).
      Action of P-ExA on monocytes resulted in: (1) inhibition of the expression of
      ICAM-1,2 molecules and their ligand LFA-1 molecule; (2) low expression of FcRI
      receptor (a ligand for Fc part of CD3 mAb); and (3) inhibition (over 90%) of the
      expression of CD14 molecule. In conclusion, P-ExA-induced anergy of T-cells
      depends on: (a) decrease in the affinity of IL-2R complex on activated T-cells;
      and (b) inhibition of the accessory activities of monocytes.

PMID- 9657259
TI  - Overexpression of cardiotrophin-1 and gp130 during experimental acute Chagasic
      cardiomyopathy.
AB  - Cardiotrophin-1 (CT-1), a cytokine with structural similarities to interleukin-6,
      has been shown to signal through gp130-dependent pathways. In vitro, CT-1
      promotes the survival and induces hypertrophy of neonatal cardiomyocytes. Since
      acute Chagas' disease involves an inflammatory response followed by chamber
      dilation, with subsequent compensatory hypertrophy, we hypothesized CT-1 and
      gp130 may participate in this disease process. Thus, we investigated expression
      and localization of these moieties during acute Chagasic cardiomyopathy. Lewis
      rats (n = 6/group) were either inoculated with cell culture-derived T. cruzi
      trypomastigotes or saline, and sacrificed 15 days later. Hearts were collected
      for histology, immunohistochemistry (IHC), mRNA, and protein analyses. Histology
      showed dense myocardial infection with amastigotes and diffuse mononuclear cell
      infiltrate. Northern blot analysis showed low level expression of CT-1 mRNA in
      controls, which was markedly elevated in infected animals (2.5-fold; P < 0.001).
      Similarly, Western blotting showed a twofold elevation of CT-1 protein in
      infected animals (P < 0.025). Likewise, levels of both gp130 mRNA and protein
      were low in controls, but were approximately threefold higher in infected
      animals. IHC showed weak and diffuse staining for CT-1 in control myocardium,
      while intense staining especially localized to the cytoplasmic region of
      cardiomyocytes, was found in infected animals. Although gp130 immunoreactivity
      was observed in both normal and infected myocardium, more intense staining was
      found in infected animals. Unlike CT-1, gp130 staining was granular, and was
      present in both the cytoplasm as well as in the perinuclear region. These data
      suggest that there is substantial overexpression of both CT-1 and gp130 in the
      heart during acute Chagasic carditis. Their overexpression may provide a
      mechanism for myocyte protection, and for development of compensatory cardiac
      hypertrophy following myocardial damage in this form of cardiomyopathy.

PMID- 9657260
TI  - MHC class II/T-cell receptor interactions potentiate secretion of IgG but not IgM
      in response to T-dependent antigens.
AB  - We have examined whether the interaction of peptide-loaded MHC molecules on the
      surface of B-cells with antigen-specific T-cell receptors (TCRs) enhances Ig
      secretion in the presence of other antigen-independent interactions in vitro. B
      cells specific for region 25-40 of beta-lactoglobulin (beta-LG) were stimulated
      in a T-cell dependent manner using plasma membranes (PM) derived from two
      different T-helper (Th) clones, culture supernatants of activated Th2 cells and
      beta-LG as a specific antigen. PM were obtained from either the beta-LG-specific
      T-cell clone H1.1 which can mediate specific TCR/MHC class II interactions as
      well as antigen-independent ones or from the D10 clone which bears a TCR of an
      irrelevant specificity and thus, can only mediate antigen-independent
      interactions. IgG, but not IgM, secretion was specifically enhanced by H1.1 PM,
      but not D10 PM in the presence of beta-LG. Furthermore, a blockade of TCR/MHC
      class II interactions using either anti-T-cell receptor, beta or anti-CD4
      monoclonal antibodies inhibited this enhanced IgG secretion in response to beta
      LG. The results show that while antigen-independent interactions between T- and B
      cells can enhance secretion of IgM antibodies, specific interactions between TCRs
      and peptide:MHC complexes stimulate B-cells to enhance secretion of IgG but not
      IgM antibodies. This mechanism may contribute to antibody secretion only from B
      cells activated through cognate interaction in vivo.

PMID- 9657261
TI  - Roles of protein phosphatase 2A in IL-6 signal transduction in Hep3B cells.
AB  - IL-6 is a pleiotropic cytokine that modulates the diverse functions of
      hepatocytes such as acute phase responses and inflammation. When human hepatoma
      cells, Hep3B cells, were treated with IL-6, p140 was phosphorylated rapidly and
      reached its maximal rate at 1 min after treatment. Okadaic acid, an inhibitor of
      protein phosphatase 1 and 2A, affected IL-6-induced p140 phosphorylation.
      Interferon regulatory factor-1 (IRF-1) is a transcription factor on the enhancer
      of type I interferons, and its gene expression is induced by IL-6. When IRF-1
      promoter-luciferase construct was transfected into Hep3B cells, okadaic acid
      increased IL-6- induced IRF-1 promoter activity. In addition, co-transfection of
      protein phosphatase 2A (PP2A) antisense constructs further increased IL-6-induced
      IRF-1 promoter activity, suggesting that PP2A is involved in IL-6 signaling. In
      addition, IL-6 directly induced the PP2A phosphorylation. PP2A phosphorylation
      was maximal at 1 min after IL-6 stimulation, but it was not induced by other
      inflammatory cytokines such as TNF-alpha or TGF-beta. Furthermore, IL-6 activated
      PP2A activity simultaneously. Taken together, these data indicate that IL-6
      modulates the functions of PP2A which is involved in downstream events of IL-6
      signaling in Hep3B.

PMID- 9657262
TI  - LAG-3 does not define a specific mode of natural killing in human.
AB  - LAG-3 is a gene localized on the band p13 of human chromosome 12, close to the NK
      gene complex (NKC), expressed on activated NK cells and encoding a receptor for
      MHC class II molecules. Recently, LAG-3 has been proposed to define a specific
      mode of natural killing in mice. The putative role of LAG-3 on human natural
      killer cytotoxicity has been examined with specific monoclonal antibodies and a
      recombinant soluble form of LAG-3. Neither the antibodies, which are able to
      block the interaction with the ligand, nor the recombinant product, which has
      retained its binding capacity for MHC class II, had an effect on the natural
      killing of various target cells. Furthermore, in redirected killing assays, none
      of these antibodies were able to modulate either positively or negatively the
      cytotoxicity. Taken together, these data show that LAG-3 has no transducing
      activity involved in NK cytotoxicity, ruling out the existence of a specific mode
      of natural killing defined by this molecule in humans.

PMID- 9657263
TI  - Humoral immune response to a 200-kDa glycoprotein antigen of Saccharomyces
      cerevisiae is common in man.
AB  - According to Heelan et al. patients suffering from Crohn's disease (CD) produce
      antibodies against a cell wall associated glycoprotein antigen gp200 of the yeast
      Saccharomyces cerevisiae, while healthy people do not. Here the authors show,
      that antibodies against this glycoprotein gp200 can also be detected in the sera
      of healthy humans. The intensity of the antibody titer which is measured by
      immunoblot experiments is independent from the state of health. The Saccharomyces
      cerevisiae specific gp200 is a highly glycosylated protein localized not only in
      the cell wall but also accumulated in the culture medium. Some of the tested sera
      from CD patients, as well as from healthy adults, also reacted with a 120-kDa
      glycoprotein which is to be found in preparations containing secreted proteins.
      Because the binding of antibodies is greatly reduced by periodate treatment of
      gp200 and by the 120-kDa polypeptide, it is very likely that their carbohydrate
      moieties are the antigenic determinants against which the specific human
      antibodies are directed. The human humoral immune response applies only to
      Saccharomyces cerevisiae antigens, because no analogous immune responses could be
      detected against antigens derived from the yeast Arxula adeninivorans.

PMID- 9657264
TI  - Anti-Lewis X antibody and Lewis X-anti-Lewis X immune complexes in Helicobacter
      pylori infection.
AB  - A molecular similarity of Lewis antigens expressed by Helicobacter pylori
      bacteria and those present in human gastric mucosa has been recognised as a cause
      of autoimmunity involved in the pathogenesis of chronic type B gastritis and
      gastric and duodenal ulcers. In this study, the expression of Lewis X
      determinants was found on 56% of H. pylori strains isolated from patients with
      chronic gastritis/gastroduodenitis. Anti-Lewis X IgG as well as Lewis X-anti
      Lewis X IgG complexes were detected in the sera from patients and even more
      frequently in the sera from healthy blood donors producing antibodies against
      surface antigens of H. pylori. It suggested that the initial H. pylori-induced
      lesions were independent of anti-Lewis X antibody production. When H. pylori
      bacteria expressing Lewis X antigen were treated with anti-Lewis X monoclonal
      antibody (mAb) of IgM isotype, they were more susceptible to ingestion by
      polymorphonuclear leukocytes (PMN) than untreated bacteria. This fact may lead us
      to believe that anti-Lewis X antibody limits the growth of H. pylori on gastric
      mucosa.

PMID- 9657265
TI  - Accumulation of IL-12-activated antitumor effector cells into lymph nodes of
      tumor-bearing mice.
AB  - Simultaneous administration of high dose of IL-12 into tumor-inoculated mice
      resulted in a marked reduction of tumor growth in parallel with the augmented
      generation of cytotoxic T-cells, natural killer (NK) cells and IFN-gamma
      producing Th cells. We found that these IL-12-activated antitumor effector cells
      preferentially accumulated in peripheral lymph nodes concomitantly with
      lymphadenopathy. However, IL-12 rather induced disappearance of antitumor
      effector cells including CD4+ T, CD8+ T and NK cells from spleen in spite of
      inducing splenomegaly. Lymph node cells obtained from IL-12-treated B16F0-bearing
      mice showed a marked IFN-gamma production in response to not only IL-2, IL-12,
      anti CD3 mAb but also B16F0 melanoma cells. Moreover, they could lyse B16F0
      melanoma cells in a long-term cytotoxicity assay. It was also confirmed that IL
      12-activated IFN-gamma producing Th1 cells were accumulated in tumor local site.
      Thus, IL-12 appeared to have a capability of stimulating selective migration of
      antitumor cells into lymph nodes and tumor local sites.

PMID- 9657266
TI  - Inhibition of B-cell receptor-antigen complex internalization by FcgammaRIIB1
      signals.
AB  - Membrane-expressed immunoglobulins are B-cell receptors (BCR) for specific
      antigens (Ag). Upon Ag engagement of the BCR, B-cells are activated to
      internalize Ag-BCR complexes, process Ag and subsequently present Ag-peptides
      loaded in class II MHC. Due to the specific nature of the BCR, the cognate
      interaction between T-cells expressing Ag-specific T-cell receptor and these Ag
      presenting B-cells occur in a highly regulated and precise manner. Accordingly,
      efficient control of T-cell activation may be achieved through regulation of Ag
      presenting B-cells. A potent form of regulation of lymphocyte responses is
      mediated by Ig end-product and anti-idiotypic antibodies via Fc-dependent
      mechanisms. In this communication, the authors present data that an anti-idiotype
      (anti-Id) Ab inhibits BCR-mediated internalization of specific Ag. Coupling of
      BCR to the cytoskeleton was also abortive in anti-Id Ab-treated B-cells.
      Inhibition by anti-Id Ab was dependent upon the presence of FcgammaRIIB1 on B
      cells. As a result of anti-Id Ab suppression, B-cells were unable to initiate
      Ca2+ responses in Ag-specific T-cells. The results suggest that co-crosslinking
      of FcgammaRIIB1 and BCR inhibits cytoskeletal coupling and internalization of the
      Ag-BCR complex thereby preventing specific Ag presentation by B-cells. Anti-Id Ab
      may mediate a negative regulatory mechanism that suppresses B-cell-mediated Ag
      specific T-cell activation.

PMID- 9657267
TI  - Modulation of NK-target cell interaction by a monoclonal antibody to K562 cells.
AB  - In order to identify the target cell recognition molecules involved in the
      interaction between natural killer (NK) cells and target cells, we have generated
      monoclonal antibodies to K562, NK-sensitive target cells. After screening by
      FACScan for the reactivity to K562, one monoclonal antibody (mAb), 4A60, was
      selected. MAb 4A60 was found to inhibit the proliferation of NK cells induced by
      IL-2 and K562 cells. However, this monoclonal antibody could not significantly
      block the conjugate formation between NK and target cells. Moreover, mAb 4A60
      only slightly inhibited the cytotoxicity of NK cells induced by IL-2. Protein
      analysis showed that mAb 4A60 recognized a 53-kDa protein of K562 cells. Taken
      together, these data suggest that mAb 4A60 inhibits the proliferation of NK cells
      induced by IL-2 and target cells, and the 53-kDa protein, a tentative ligand of
      this mAb of K562, may be involved in this process.

PMID- 9657268
TI  - Variable gene segment-specific N-insertions at the signal joint of T-cell
      receptor Vbeta-Dbeta recombinations.
AB  - The V(D)J recombination of immunoglobulin and a T-cell receptor generates two
      species of DNA junctions, a coding joint and a signal joint. Non-templated
      nucleotides (N-nucleotides) are inserted in these DNA junctions. We analyzed the
      N-insertion at signal joints generated by the Vbeta-Dbeta recombinations. N
      insertions were detected at signal joints of Vbeta2, Vbeta3, Vbeta10, Vbeta18 and
      Vbeta14 but not in Vbeta8 and Vbeta7. These data show that the N-insertion at
      signal joints is dependent on the Vbeta locus used for the recombination. We
      suggest that the regional chromosomal configuration may differ in recombinase
      accessibility.

PMID- 9657269
TI  - Cytofluorometric detection of mitochondrial alterations in early CD95/Fas/APO-1
      triggered apoptosis of Jurkat T lymphoma cells. Comparison of seven mitochondrion
      specific fluorochromes.
AB  - It is commonly accepted that mitochondria undergo major changes early during the
      apoptotic process and that these alterations are critical for the death/life
      decision. Here we report that Jurkat T cell leukemia cells exhibit a perturbed
      incorporation of potential-sensitive fluorochromes. After 6 h of CD95/Fas/APO-1
      crosslinking, a significant fraction of still normal-sized Jurkat cells exhibit a
      decreased incorporation of three different cationic lipophilic dyes commonly used
      for the quantitation of the mitochondrial transmembrane potential (deltapsi(m)):
      DiOC6(3), chloromethyl-X-rosamine, and tetramethylrhodaminemethylester. In
      contrast, upon induction of apoptosis, cells tend to exhibit an increase in the
      fluorescence obtained with rhodamine 123. The increased rhodamine 123
      fluorescence into cells undergoing apoptosis is not affected by labeling in the
      presence of the protonophore m-chlorophenylhydrazone and thus cannot be
      attributed to a change in the deltapsi(m). Six hours after CD95 ligation no
      changes are found among normal-sized cells in the incorporation of mitotracker
      green and nonylacridine orange, which both measure mitochondrial mass. However, a
      fraction of cells exhibit an increased staining with the Apo2.7 antibody which
      detects a mitochondrial antigen generated during apoptosis. These findings
      underline the importance of using adequate fluorochromes for the quantitation of
      mitochondrial changes occurring during early apoptosis. Moreover, they cast
      doubts on those studies that, using rhodamine 123, hypothesized that apoptosis
      would be associated with a stable or increased deltapsi(m).

PMID- 9657270
TI  - Mouse NK1.1+ cytotoxic T cells can be generated by IL-2 exposure from lymphocytes
      which express an intermediate level of T cell receptor.
AB  - NK-like T cells which express the NK1.1 molecule and CD3 (or TCR) of intermediate
      level (CD3int or TCRint cells) were recently demonstrated to be present in
      various immune organs, and to have NK-like cytotoxic activity against NK target
      cells. In this study, we investigated whether NK1.1- T cells could express NK1.1.
      We found that NK1.1+ TCRint cells were much more abundant in the liver (20%) than
      in the spleen (2%). When hepatic and splenic mononuclear cells (MNCs) were
      cultured either in the absence of IL-2 or in the presence of CD3/TCR cross
      linking, the original NK1.1+ TCRint cells disappeared. However, when they were
      cultured in the presence of a high dose of IL-2 for 4 days, a new type of NK1.1+
      T cell was formed to the extent of approximately 15-20%, and the liver and spleen
      contained similar percentages of this new type of NK1.1+ T cells. The phenotypes
      of the original and the new type of NK1.1+ T cells were clearly distinct. The
      freshly obtained NK1.1+ TCRint cells consisted of double-negative (DN) CD4-CD8-
      cells and single-positive (SP) CD4+ cells, whereas the new type of NK1.1+ T cells
      predominantly consisted of DN CD4-CD8- cells and SP CD8+ cells and expressed a
      high level of CD3 (CD3high or TCRhigh cells). When NK1.1- cells or IL-2 receptor
      beta-chain (IL-2Rbeta)- cells were isolated from the liver and spleen, and
      cultured in the presence of IL-2 for 4 days, NK1.1+ T cells were generated from
      NK1.1- cells, but not from IL-2Rbeta- cells. Our results suggested that the NK1.1
      cells, but not IL-2Rbeta- cells, contained the precursor of IL-2-stimulated
      NK1.1+ TCRhigh cells. When purified NK1.1- IL-2Rbeta+ TCRint cells were cultured
      in the presence of IL-2 for 4 days, approximately 10% of the cells became NK1.1+
      TCRhigh cells. Approximately 60% of the purified NK1.1+ TCRint cells lost NK1.1
      expression. The IL-2-stimulated NK1.1+ TCRhigh cells that had arisen from NK1.1-
      TCRint cells exerted an NK cell-like cytotoxic activity similar to that of the
      original NK1.1+ T cells. Thus, NK1.1- TCRint cells could express NK1.1 and exert
      NK-like cytotoxic activity regardless of their origin. It appears that NK1.1+
      TCRhigh cells can only be induced through an IL-2-stimulation pathway but not via
      CD3/TCR cross-linking.

PMID- 9657271
TI  - Alkaline phosphatase activity is expressed in murine splenic B-lymphocytes
      sensitized in vivo with Tetanus toxoid.
AB  - Alkaline phosphatase (APase) activity and proliferative response to Tetanus
      toxoid (TT) were measured in murine splenic lymphocytes immunized in vivo with
      TT. APase activity was enhanced in TT-stimulated B-lymphocytes concomitant with
      an increase in the proliferative response in a dose-dependent manner.
      Cytochemical staining for APase using beta-naphthyl phosphate also showed an
      increase in APase positive cells in TT-stimulated lymphocyte population. The
      results suggest that membrane APase expression is a physiological phenomenon
      occurring in antigen-stimulated B-lymphocytes.

PMID- 9657272
TI  - Protein kinase C: a potential pathway of macrophage activation with cisplatin.
AB  - Cisplatin (CP) has been reported to activate murine macrophages to tumoricidal
      state, however, its mechanism of action is not known. In the present study it is
      reported that the production of: (a) interleukin-1 (IL-1); (b) tumor necrosis
      factor (TNF); (c) nitric oxide (NO); and (d) macrophage-mediated cytotoxicity by
      cisplatin-treated bone marrow-derived macrophages were inhibited by PKC
      inhibitors H-7 and chelerythrine chloride. Also, it was observed that treatment
      of macrophages with CP resulted in the translocation of PKC from the cytosol to
      the membrane fraction. These findings suggest the involvement of PKC in the
      activation of bone marrow-derived macrophages with cisplatin.

PMID- 9657273
TI  - Requirement of the CD8+ or CD4+ T lymphocyte subsets for the rejection of
      lymphoma and fibrosarcoma grafts studied in gene knockout hosts.
AB  - Rejections of the retrovirus induced lymphomas (ALC and RBL-5) and the
      methylcholanthrene (MCA) induced fibrosarcoma (MC57X) grafts were tested in
      syngeneic CD8 and CD4 single and double knockout C57BL/6 mice. The results with
      the lymphomas showed that the CD8+ T cell deficiency prevented the development of
      rejection response induced by immunization. Deficiency of the CD4+ T subset
      abrogated also the rejection of ALC. Immunity against the fibrosarcoma cells
      developed in both type of single knockout mice, but not in the ones which lacked
      both CD4+ and CD8+ T cells. Thus CD8+ T cells were required for rejection of the
      lymphoma cells, while the CD4+ T cells only mediated a weak response. In absence
      of CD8+ T cells, CD4+ T cells were sufficient to reject the fibrosarcoma cells.

PMID- 9657274
TI  - Phospholipid-binding activity of human mannan-binding lectin.
AB  - Some C-type lectins possess phospholipid-binding ability, which may be of
      physiological importance. Human mannan-binding lectin (MBL) was found to bind
      specifically to solid-phase phosphatidylserine (PS), phosphatidylinositol (PI)
      and phosphatidylcholine (PC), but not cardiolipin (CL), in a concentration
      dependent manner. This property was inhibited by EDTA and by monosaccharides, and
      exhibited a similar pH dependence to the carbohydrate (mannan)-binding activity
      of MBL. These findings may be of immunological relevance.

PMID- 9657275
TI  - Imbalanced distribution of IgM and IgG antibodies against Plasmodium falciparum
      antigens and merozoite surface protein-1 (MSP1) in pregnancy.
AB  - In malaria endemic areas, pregnancy is assumed to be associated with a specific
      reduction in immunity to Plasmodium falciparum malaria. To understand some of the
      mechanisms which underlie such a poor immunity, we have attempted to examine the
      frequency and distribution of IgM and IgG antibodies to a crude antigenic extract
      of parasitized erythrocytes and to the merozoite surface protein-1 (MSP1), in a
      population of mothers compared to control non-pregnant women, all living in Dakar
      and suburbs. Specifically, this work describes: (i) the responses of mothers and
      control women; (ii) the balance between IgM and IgG responses; and (iii)
      responses to malarial antigen and to MSP1. An unexpected balance between P.
      falciparum-specific IgM and IgG is shown, associated with a substantial increase
      in anti-MSP1 IgM, and a decrease in anti-MSP1 IgG in parturients.

PMID- 9657276
TI  - Differential induction of immunoglobulin G subclasses by immunization with DNA
      vectors containing or lacking a signal sequence.
AB  - The route and method used to immunize mice with antigen-expressing DNA plasmids
      have an impact on the resulting T-helper cell response and IgG subclass
      distribution. Previous findings further indicate that the intracellular targeting
      of expressed antigens influences the differentiation of naive T-cells into either
      a Th1 or a Th2 type of response. In the present study, we analyzed the levels of
      IgG1 and IgG2a antibodies, as correlates of Th2 and Th1 responses, respectively,
      after intramuscular injection of mice with plasmids encoding a chimeric protein
      containing a Plasmodium falciparum blood stage antigen expressed in two different
      forms. One plasmid expresses the antigen in a secreted form as it is preceded by
      a signal sequence while expression from the other plasmid, lacking this sequence,
      results in cytoplasmic localization of the antigen. Mice immunized with the
      plasmid encoding secreted antigen responded with predominantly IgG1 antibodies.
      In contrast, sera from mice immunized with the plasmid expressing cytosolic
      protein displayed a mixed IgG1/IgG2a profile. In line with previous findings, our
      results suggest that the intracellular targeting of proteins expressed by DNA
      plasmids is an important factor for the differentiation of Th cells and the
      resulting subclass pattern of IgG responses.

PMID- 9657277
TI  - Frequency of the delta ccr5 deletion allele in the urban Brazilian population.
AB  - Studies on screening genes conferring resistance to HIV-1 and AIDS onset have
      shown a direct relationship between a 32 base pair (bp) deletion in the CCR5 beta
      chemokine receptor gene (delta ccr5 mutant allele) and long survival of HIV-1
      infected individuals bearing this mutation. These findings led to an interest in
      studies of delta ccr5 allele distribution in human populations. In the present
      study, polymerase chain reactions (PCR) in genomic DNA samples, using specific
      CCR5 oligonucleotide primers surrounding the breakpoint deletion, detected a 193
      bp product from the normal CCR5 allele and a 161-bp product from the 32-bp
      deletion allele. In an investigation of the urban Brazilian population we
      detected a 93% frequency of normal CCR5/CCR5 homozygous individuals and a 7%
      frequency of CCR5/delta ccr5 heterozygous individuals. The frequency of the delta
      ccr5 mutant allele in this population is 0.035; however, no homozygous delta ccr5
      individual has been detected thus far. This is the first evidence for the
      contribution of the delta ccr5 allele to the genetic background of the urban
      Brazilian population, which is characterized by intense ethnic admixture. These
      findings open perspectives for further studies on the relationship between delta
      ccr5 allele frequency and AIDS onset in high-risk HIV-1 exposures individuals.

PMID- 9657278
TI  - The use of dogs as second species in regulatory testing of pesticides. I.
      Interspecies comparison.
AB  - The relevance of studies in dogs on regulatory testing of pesticides was examined
      retrospectively using data of 216 pesticides (acaricides, fungicides, growth
      regulators and hormones, herbicides, insecticides, molluscicides, nematicides,
      rodenticides, synergists for insecticides) submitted for regulatory purposes
      during the past 40 years to the Federal Institute of Health Protection of
      Consumers and Veterinary Medicine (BgVV), the competent national authority in
      Germany. At first the relevance of the no-observed-effect levels (NOEL) for
      safety assessment was evaluated for each chemical in 4-week (subacute), 13-week
      (subchronic) and 52/104-week (chronic) toxicity studies carried out on dogs, rats
      and mice. After subchronic and chronic application of fungicides the sensitivity
      of rats and dogs to the toxic chemicals was quite similar. However, the dog was
      generally a more sensitive species to toxic effects of insecticides than rat and
      mouse. On the other hand the NOEL was lower in the rat than the dog in chronic
      studies on herbicides. When the lowest-observed-effect level (LOEL) was evaluated
      in animal species, the dog was the most sensitive in approximately 15% of the
      studies. Mice were found to be the most sensitive species only in approximately
      1% of the studies on 216 pesticides. Comparison of organ specific toxicity at the
      LOEL in subacute studies on fungicides and herbicides revealed a poor correlation
      of target-specific organ toxicity across species. However, in the subchronic and
      chronic studies (13 and 52/104 weeks) no significant differences in species
      specific organ toxicity were observed in the three species rat, mouse and dog.
      The only exception were haematoxic effects in chronic studies on herbicides,
      which were more frequent in dogs (40%) than in rats and mice (20%). The results
      support the established concept that studies on dogs and rats are important for
      the safety assessment of pesticides, while studies on mice do not provide further
      information, except for detection of an oncogenic potential which is a further
      controversial issue. Further analysis of subacute, subchronic and chronic studies
      in dogs should reveal if all of the studies are essential for safety assessment
      of pesticides.

PMID- 9657279
TI  - Application of the queueing theory with Monte Carlo simulation to inhalation
      toxicology.
AB  - Various models have been developed in modelling of inhalation toxicology. The
      deterministic approach, which has been used to date in most of the models, needs
      to consider numerous factors, e.g. anatomical structure, breathing frequency,
      humidity, metabolism rate, partition coefficients, pulmonary ventilation,
      perfusion rates, unidirectional/cyclic air flow, non-steady-state, steady-state,
      etc. In the present study, a stochastic approach was used in the modelling of
      inhalation toxicology, because there is a phenomenological analogy between the
      queueing system and respiratory system dealing with inhaled toxicants. Using the
      queueing theory, the amounts of toxicants in the respiratory system, the time
      needed to remove the accumulated amounts of toxicants from the respiratory
      system, etc. can be estimated. The Monte Carlo simulation of queueing process was
      performed to analyse cigarette smoking, and shows the potential use of the
      queueing theory in inhalation toxicology.

PMID- 9657280
TI  - Induction of CYP2A5 by pyrazole and its derivatives in mouse primary hepatocytes.
AB  - Mouse liver CYP2A5 is induced by several structurally unrelated compounds. In
      intact mouse liver, pyrazole (PYR) and 4-hydroxypyrazole (4-OH) induce
      selectively the expression of CYP2A5 while expression of other CYPs is decreased.
      In this study we exposed mouse primary hepatocytes to PYR, 4-OH, 4-methylpyrazole
      (4Me; 0.1-20 mM) and 4-iodopyrazole (4-I; 0.1-5.0 mM). PYR and its derivatives
      increased coumarin 7-hydroxylase activity, with 4-1 and 4-OH being the strongest
      inducers, by 114-fold and 41-fold, respectively. However, only 4-1 treatment
      increased markedly the CYP2A5 protein content. CYP2B9/10-mediated
      pentoxyresorufin O-deethylase activity (PROD) was decreased by 80% by 4-Me and 4
      1, and by 50% by 4-OH while PYR had no marked effect. PYR and 4-Me increased 2-
      to 3-fold the CYPA1/2-mediated ethoxyresorufin O-deethylase activity (EROD) while
      4-OH and 4-1 had no marked effect on this enzyme. The time of exposure markedly
      affected the inducibility of 4-OH such that induction was 7-fold stronger when it
      was added to the incubation medium 24 h after the isolation of hepatocytes
      compared to exposure 3 h after their isolation. Cimetidine prevented the
      induction of coumarin 7-hydroxylase activity by PYR and 4-OH by 46 and 74%,
      respectively indicating that their effects on the expression of CYP2A5 are, at
      least partly, mediated via their metabolites. The data demonstrate that the
      regulation of CYP2A5 is different from other monooxygenases and that the effects
      of pyrazole and its derivatives are different in vivo and in vitro. Also, the
      timing of exposure markedly affects the inducibility of 4-OH in hepatocytes.

PMID- 9657281
TI  - Mutagenic properties of 1,2,3,4-tetrahydronaphthaline-1-hydroperoxide, a model
      compound for organic peroxides in Diesel exhaust.
AB  - The genotoxicity of the organic peroxide 1,2,3,4-tetrahydronaphthaline-1
      hydroperoxide (or tetraline-1-hydroperoxide, THP) was investigated in the Ames
      assay without a metabolic activating system using Salmonella typhimurium strains
      TA 98, TA 100, and TA 102. THP served as a model compound for higher organic
      peroxides, which can arise from autoxidation of hydrocarbons, e.g. in Diesel
      exhaust. While THP induced no mutagenic response in S. typhimurium TA 98, it was
      directly mutagenic in strains TA 100 and TA 102. These data, along with findings
      on mutagenic properties of other alkyl hydroperoxides, suggest that such
      compounds deserve further investigation regarding their genotoxic potential and
      occurrence in the environment.

PMID- 9657282
TI  - The nephrotoxicity and hepatotoxicity of 1,1,2,2-tetrafluoroethyl-L-cysteine in
      the rat.
AB  - Recent studies have shown that tetrafluoroethylene is a renal and hepatic
      carcinogen in the rat. In this study, we have examined the ability of a single
      i.p. dose of 1,1,2,2-tetrafluoroethyl-L-cysteine (TFEC), a major metabolite of
      tetrafluoroethylene, to produce hepatic and renal injury in male and female rats.
      We have also examined the effect of blocking the renal organic anion transport
      system with probenecid and of inhibiting the activity of cysteine conjugate beta
      lyase with aminooxyacetic acid on the extent of renal injury produced by TFEC.
      Doses of > or = 12.5 mg/kg TFEC produced renal tubular necrosis to the pars recta
      of the proximal tubules within 24 h in both male and female rats. This was
      associated with an increased kidney to body weight ratio and plasma urea at doses
      of > or = 25 mg/kg. No consistent evidence of liver injury was seen at doses up
      to 50 mg/kg TFEC in rats of either sex, although occasional vacuolation of
      hepatocytes and a small dose-related increase in liver to body weight ratio was
      observed. Prior treatment of female rats with probenecid completely prevented the
      renal injury produced by either 25 or 50 mg/kg TFEC as judged by plasma urea and
      histopathology. However, prior treatment of female rats with aminooxyacetic acid
      afforded no protection against the nephrotoxicity produced by either TFEC or the
      cysteine conjugate of hexachloro-1,3-butadiene. Thus no major sex difference in
      nephrotoxicity in the rat was seen with TFEC, while accumulation of TFEC, or its
      N-acetyl derived metabolite, into renal proximal tubular cells via a probenecid
      sensitive transport system appears to be a key event in the mechanism of
      nephrotoxicity. The lack of protection observed with the cysteine conjugate beta
      lyase inhibitor, aminooxyacetic acid, may reflect the inability to completely
      inhibit the mitochondrial form of this enzyme and thereby prevent the formation
      of the reactive metabolite. Our acute studies provide no insight concerning the
      liver carcinogenicity of tetrafluoroethylene.

PMID- 9657283
TI  - Stimulation of liver heme oxygenase in hexachlorobenzene-induced hepatic
      porphyria.
AB  - We have measured liver heme oxygenase, a heat shock protein known to be increased
      under conditions of oxidative stress, to obtain additional evidence for an
      oxidative stress mechanism in hepatic uroporphyria induced by hexachlorobenzene
      (HCB). We have studied heme oxygenase at different times during HCB treatment and
      in two strains of rats (Agus and Wistar strains), which are known to differ in
      their sensitivity to the porphyria-inducing properties of HCB, in order to
      ascertain whether the same time course and genetic differences known to exist for
      the induction of porphyria also apply to hepatic oxidative stress. HCB induced
      heme oxygenase and accumulation of porphyrins in the liver of rats of both
      strains; no significant difference was found between the two strains in the HCB
      induced heme oxygenase activity. The increased activity of the enzyme was first
      detected during the early phases of treatment, when a modest increase in liver
      porphyrins was observed; heme oxygenase remained at induced levels for several
      weeks during HCB treatment, and was still raised when an increase in total liver
      iron content and the onset of marked porphyria were also found. In contrast to
      the effects of HCB, phenobarbitone sodium (given in the drinking water for up to
      4 weeks) produced similar elevations of total liver cytochrome P450 as HCB, but
      did not stimulate heme oxygenase or increase the total liver content of either
      iron or porphyrins. These results are compatible with an oxidative stress
      mechanism in HCB-induced liver toxicity and porphyria, but also suggest the
      existence of successive stages in the induction of hepatic porphyria, with more
      than one mechanism contributing to the marked accumulation of uroporphyrin.

PMID- 9657284
TI  - Elucidation of mitochondrial effects by tetrahydroaminoacridine (tacrine) in rat,
      dog, monkey and human hepatic parenchymal cells.
AB  - Tetrahydroaminoacridine (tacrine) causes morphological and functional changes in
      the endoplasmic reticulum, ribosomes, and mitochondria in the liver of humans and
      animals. In order to investigate species differences as well as to understand the
      morphological changes, we examined the effects of tacrine on respiration and
      electron transport in mitochondria isolated from rat, dog, monkey, and human
      liver. Tacrine produced significantly decreased respiratory control ratios (RCR)
      in all species at concentrations ranging from 5 to 25 microg/ml. Human
      mitochondria were more sensitive to tacrine effects with RCR decreased 24% at 5
      microg/ml while other species were unaffected at this concentration. The tacrine
      effects were characterized by increased hepatic mitochondrial State 4 respiration
      in rats and decreased State 3 respiration in humans. Mitochondria from aged rats
      were more sensitive to the effects of tacrine than mitochondria from young
      animals, with significantly decreased RCR at 10 microg/ml in aged rats while
      mitochondria from young rats were unaffected at this concentration. Concomitant
      with the respiratory changes, mitochondrial DNA synthesis was impaired. Since
      tacrine undergoes extensive biotransformation, we also explored the possibility
      that metabolites could exert detrimental effects. The ranking order of potency
      for decreasing RCR caused by monohydroxylated metabolites was: tacrine > 4-OH and
      7-OH > 2-OH, 1-OH, and velnacrine with the latter group of metabolites having no
      effect on mitochondrial respiration at concentrations up to 50 microg/ml. In vivo
      administration of 20 mg/kg tacrine to rats for up to 20 days caused a paradoxical
      increase in RCR and P/O on Day 1 and decreased RCR on Days 9 and 20, the later
      findings being consistent with in vitro data. From these data we propose that
      tacrine does not necessarily have to be metabolized to exert effects on
      mitochondria at different sites in the electron transport chain that differ among
      species. These effects are exacerbated in mitochondria from older animals and
      humans appear to be more sensitive than the laboratory animals studied.

PMID- 9657285
TI  - Evaluation of toxicity indicators in rat primary astrocytes, C6 glioma and human
      1321N1 astrocytoma cells: can gliotoxicity be distinguished from cytotoxicity?
AB  - A comparison was made of rat primary astrocytes, C6 glioma cells pre-treated with
      dibutyryl cyclic AMP, and the human astrocyte 132N1 cell line using a range of 40
      compounds and the neutral red (NR) assay. The 40 chemicals included substances
      known to be toxic to astrocytes or neurons, to be generally cytotoxic or not
      thought to be toxic to nervous tissue. For those compounds which were toxic,
      changes in glial fibrillary acidic protein (GFAP) levels were measured in the
      primary and C6 cultures, and changes in vimentin and S-100 measured in the C6
      cells. The number of compounds with EC50 values < 2000 microg/ml for the NR assay
      for the different cell cultures were as follows: primary astrocytes, 19; C6
      cells, 15; and 1321N1 cells, 11. The log of the EC50 values for the NR assay for
      the test compounds between the three cell types was not significantly different
      at the 5% level by paired Student's t-test. For the toxic substances the
      correlation coefficients of the EC50 values between primary cells and the C6 or
      1321N1 cells were r > 0.5, and between the C6 and 1321N1 cells r > 0.9. For GFAP
      there was a similar degree of correlation in EC50 values between the different
      cell types. The GFAP, vimentin and S-100 levels showed similar EC50 values for
      the toxicants, but were not as sensitive as the NR assay. The toxic substances
      caused altered morphology in the primary, C6 and 1321N1 cells, with increased
      branching of cell processes. The combined astrocyte systems identified 8 out of 9
      substances reported to be toxic to astrocytes in vivo, together with substances
      which have general cytotoxic properties. A number of substances (including the 1
      out of 9 reported gliotoxic substances), which may primarily affect neurons,
      which may affect nervous tissue after long-term exposure, or which are not
      thought to be toxic to nervous tissue, were not detected. The astrocyte systems
      positively identify gliotoxic and cytotoxic substances and will allow detailed
      mechanistic studies to be made on the different underlying mechanisms.

PMID- 9657286
TI  - Effects of vitamin A pretreatment on nickel-induced lipid peroxidation and
      concentration of essential metals in liver, kidney and lung of mice.
AB  - In the present study we report the effects of pretreatment with large doses of
      vitamin A (Vit A, retinol) on hepatic, renal and pulmonary lipid peroxidation,
      and Ni and essential metal (Fe, Cu, Zn and Ca) concentrations in mice acutely
      exposed to nickel. Vitamin A (250,000 IU/kg per day) was administered by oral
      gavage to ICR mice for 7 days. On the 8th day, NiCl2 (5 mg Ni/kg body wt.) was
      injected i.p. to Vit A- or vehicle-pretreated mice. Vitamin A pretreatment alone
      did not alter lipid peroxidation in liver, kidney and lung. Lipid peroxidation in
      liver, kidney and lung was increased after treatment with NiCl2 alone. The extent
      of lipid peroxidation levels in Vit A + Ni treated mice was enhanced in liver,
      but reduced in kidney and lung. The Ni concentration in these three organs was
      below the detection limit (0.09 microg/g) in control and Vit A-pretreated mice.
      The accumulation of Ni in Vit A + Ni treated mice was increased in liver, but
      decreased in kidney and lung compared to Ni-treated mice. The concentrations of
      Fe, Cu, Zn and Ca in these organs were significantly increased in Ni-treated
      mice. In Vit A + Ni treated mice, compared to Ni-treated mice, hepatic Fe was
      significantly increased while Cu, Zn and Ca levels were reduced, but still higher
      than those of control and Vit A-treated mice. In the kidney of Vit A + Ni treated
      mice, the increase of Cu, Fe, and Zn but not Ca, was reduced and not
      significantly different from control and Vit A-treated mice. Pretreatment with
      Vit A reduced the increased Fe, Cu, Zn and Ca concentration in the lung caused by
      Ni injection. We therefore conclude that the effect of Vit A pretreatment on Ni
      toxicity is organ-dependent.

PMID- 9657287
TI  - Albert Einstein and his mentor Max Talmey. The seventh Charles B. Snyder Lecture.
AB  - While he was a student at the Munich medical school, Max Talmey strongly
      influenced the education of Albert Einstein. Their association occurred during
      five years of Einstein's second decade. They lost contact for many years after
      each left Munich. Talmey emigrated to the United States and practiced medicine,
      mainly ophthalmology, in New York City. He made significant contributions to
      medicine, to the popularization of Einstein's work, and to the development of
      international languages. The relationship of Talmey and Einstein was rekindled
      when Einstein visited and later moved to the United States.

PMID- 9657288
TI  - Wooden eyeglass cases.

PMID- 9657289
TI  - Changing trends in the etiologic diagnosis of uveitis.
AB  - Just as different fads that seize the imagination of the general public are often
      carried to excess, so diagnostic or therapeutic fads may take over in the
      practice of medicine. Analysis of 33 surveys of the causes of uveitis reported by
      ophthalmologists over the course of 120 years shows how some diagnoses such as
      syphilis and tuberculosis fell from favor because tests ruled out these diseases,
      whereas others such as toxoplasmosis became popular because of the finding of the
      organism in a few cases by a famous ophthalmic pathologist. Yet others (pars
      planitis, sarcoidosis) were not even causes of disease, but rather merely
      descriptive, or the ocular component of a systemic disease whose etiology and
      pathogenesis remain unknown. We will examine the waxing and waning of these
      diagnostic categories and the impressive confidence of some clinicians in their
      own diagnostic acumen as they made diagnoses often unsupported by objective
      evidence.

PMID- 9657290
TI  - Stephen Girard (1750-1831): a one-eyed American patriot.
AB  - Stephen Girard trader, banker, millionaire, and patriot lived 81 full and
      exciting years. Apparently born with a blind or amblyopic right eye, he emigrated
      from Bordeaux, France, via Santa Domingo to the United States, and finally
      settled in Philadelphia, where he developed a successful maritime trade.
      Ultimately, Girard became the first multimillionaire in the United States.
      Extremely generous, he often walked from his home in the center of Philadelphia
      to his farm in what is now South Philadelphia distributing shoes to needy
      children. Probably Girard's most heroic gestures were his gallant fight against
      the yellow fever epidemic in 1793 and his loan to the U.S. government during the
      War of 1812, which allowed the bankrupt country to continue the conflict and
      ultimately to win the war.

PMID- 9657291
TI  - Notes on Voltaire's 'The elements of Sir Isaac Newton's Philosophy'.

PMID- 9657292
TI  - Little known aspects of Jules Gonin's life.

PMID- 9657293
TI  - The history of the evil eye and its influence on ophthalmology, medicine and
      social customs.
AB  - Belief in the evil eye is one of the oldest and most widespread superstitions in
      the world. The concept of the evil eye has influenced present day ophthalmology,
      medicine, and social customs. Oculus sinister (OS), the serpent and the staff of
      Asclepius, the symbol of RX, and many social customs are historically related to
      the evil eye.

PMID- 9657295
TI  - The great mind of Thomas Young (1773-1829).

PMID- 9657294
TI  - The Origin of Species, Man's Place in Nature and the naming of the calcarine
      sulcus.
AB  - In The Origin of Species by Means of Natural Selection of 1859, Charles Darwin
      provided a detailed, coherent proposal: species changed into new ones by the
      action over time of natural forces in the environment acting continuously on the
      variations always present within species. Readers immediately extrapolated
      Darwin's argument concerning lower animals to the implications for humans, and
      its denial of a special creation of humans. In opposition to Darwin's theory,
      Britain's preeminent paleontologist and comparative anatomist, Richard Owen,
      argued that man was unique among all creation in the possession of a particular
      structure within the brain, the 'Hippocampus minor'. Darwin's great defender,
      Thomas Huxley, demonstrated that this structure also existed in monkeys and apes,
      and that it was simply a manifestation of a 'particular sulcus' in the posterior
      cerebral cortex, which he named as the 'calcarine' sulcus. The home of the visual
      striate cortex was thus named as part of the controversy surrounding the birth of
      evolutionary theory, soon to be accepted as the great unifying concept in all of
      biology.

PMID- 9657296
TI  - Ophthalmic injuries and civil war medicine.

PMID- 9657297
TI  - Evolution of the British ophthalmoscope.

PMID- 9657298
TI  - Unknown ancient Greek ophthalmological instruments and equipment.
AB  - Discoveries of some ancient medical instruments and equipment found in the
      Hellenic world have been published in magazines of general interest and in a rare
      Greek medical journal, yet none caught the attention of ophthalmologists. Among
      these instruments are two forms of the famous 'Kenteterion', dating from the
      Hellenistic period, used for the couching of cataract. These were found on the
      island of Milos in the last century. Two magnifying lenses of the Archaic period
      from the recent Cretan excavations gave us the opportunity to discuss the problem
      of their medical use. The two drop-bottles from the excavations on Cyprus and at
      Tanagra, which are also described, seem to be of medical, and possible
      ophthalmological, use.

PMID- 9657299
TI  - C.S. O'Brien: founder of the Department of Ophthalmology, the University of Iowa.
AB  - Cecil Starling O'Brien, M.D. (1889-1977), was the founder (1927) of the
      Department of Ophthalmology at the University of Iowa, and he is credited with
      the establishment of a strong department that has made many important
      contributions to ophthalmology. The surviving O'Brien residents were interviewed
      on videotape, and this article is a composite of their memories together with a
      brief biographical sketch of Dr. O'Brien.

PMID- 9657300
TI  - Cornelius Rea Agnew, M.D., and the code of ethics of the Medical Society of the
      State of New York.

PMID- 9657301
TI  - The effect of forskolin on the sound-evoked potentials in the guinea pig cochlea.
AB  - The effect of forskolin (FSK) on cochlear sound-evoked potentials was examined in
      the guinea pig. The perfusion of the scala vestibuli (SV) with FSK (2 x 10(-4) M)
      produced a significant increase in the amplitude of negative summating potential
      (- SP) with no change in cochlear microphonics (CM) amplitude, and a significant
      decrease in the amplitude of compound action potential (CAP) with a significant
      prolongation of N1 latency and a 20 dB CAP threshold elevation. The results lead
      us to speculate that FSK-induced changes may be involved in the transient
      formation of endolymphatic hydrops.

PMID- 9657302
TI  - Failure of forskolin to elevate the endocochlear potential in experimental
      endolymphatic hydrops of the guinea pig.
AB  - The effect of forskolin (FSK) on the endocochlear potential (EP) in scala media
      (SM) was examined in experimental endolymphatic hydrops of the guinea pig. Two
      weeks after obliteration of the endolymphatic sac the EP of hydroptic ears and
      that of the contralateral control ears were measured by means of microelectrodes.
      The perfusion of scala vestibuli (SV) with FSK (200 microM) produced EP elevation
      in the contralateral control ears but failed to do so in the experimental
      hydroptic ears. Histological examination of experimental endolymphatic hydrops
      showed mild hydrops with intact appearance of outer and inner hair cells, and the
      stria vascularis. The mechanism underlying the failure of FSK to elevate the EP
      in experimental endolymphatic hydrops is discussed.

PMID- 9657303
TI  - Effect of acetazolamide on cation concentration in the endolymph of the
      endolymphatic sac.
AB  - Acetazolamide (ACTZ), a carbonic anhydrase inhibitor, has been reported to
      decrease the endolymphatic sac (ES) DC potential (ESP) in the guinea pig. To
      assess the involvement of cation transport in the ESP change by ACTZ we examined
      the effect of ACTZ upon the K+ and Na+ activities of the ES endolymph in the
      guinea pig using ion-sensitive microelectrode. ACTZ (10 mg/kg), a dose that
      produces the ESP maximum reduction, produced a significant increase in Na+
      activity of the ES endolymph with no change in K+ activity. The results suggest
      that Na+ transport may be directly or indirectly involved in ESP reduction by
      ACTZ, and that a Na(+)-H+ exchanger may be involved in Na+ influx pathway from
      endolymph to the ES epithelial cells.

PMID- 9657304
TI  - Effect of intravenous vasopressin on endocochlear potential and systemic blood
      pressure in the guinea pig.
AB  - The effects of intravenous arginine-vasopressin (AVP) on the endocochlear
      potential (EP) and systemic blood pressure (BP) were examined in the guinea pig.
      Intravenous AVP (10(-7) M) elevated BP significantly but did not change EP. AVP
      (10(-8) M) produced a significant decrease in the amplitude of EP but did not
      change mean blood pressure significantly. AVP at 10(-9) M did not affect EP or
      BP. These results suggest that intravenous AVP might have an inhibitory effect on
      EP.

PMID- 9657305
TI  - Selective expression of mercurial-insensitive water channel (AQP-4) gene in
      Hensen and Claudius cells in the rat cochlea.
AB  - We investigated the cellular localization of mercurial-insensitive water channel
      (MIWC) mRNA in the rat cochlea. MIWC gene expression was detected in the
      supporting cells in Corti's organ. The function of these supporting cells is not
      clear, but the results suggest that they reabsorb water and play a role in
      maintaining the ionic balance of inner ear fluids.

PMID- 9657306
TI  - The neurosteroid pregnenolone sulfate excites medial vestibular nucleus neurons.
AB  - To examine the relationship between neurosteroids and vertigo we performed
      electrophysiological studies to determine whether pregnenolone sulfate (PS)
      affects the activity of medial vestibular nucleus (MVN) neurons in alpha
      chloralose-anesthetized cats. Single neuronal activities in the MVN were recorded
      extracellularly using a glass-insulated silver wire microelectrode attached along
      a seven-barreled micropipette. 3 mM PS, 1 M glutamate and 3 mM NaCl were applied
      microiontophoretically in the immediate vicinity of the target neurons. The
      effects of these drugs were then examined on type I and type II neurons,
      identified by their responses to horizontal and sinusoidal rotations. The
      iontophoretic application of PS dose-dependently increased the spontaneous firing
      of both type I and type II neurons. The larger increase in firing was observed in
      type I neurons as compared with type II neurons following the PS application.
      These results suggest that PS excites types I and II neurons differentially,
      presumably resulting in a disturbance of harmony of the vestibulo-ocular reflex
      with ensuing development of vertigo.

PMID- 9657307
TI  - Vestibular neuronal function of cats following unilateral vertebral artery
      occlusion.
AB  - Since vertigo is known to be caused by vertebrobasilar arterial occlusive disease
      (ex. vertebrobasilar insufficiency; VBI), an electrophysiological study was
      performed to examine the effects of a unilateral vertebral artery (VA) occlusion
      on the neuronal activities of the medial vestibular nucleus (MVN) and vestibular
      ganglion (VG) in alpha-chloralose-anesthetized cats. Single neuronal activity in
      the MVN and VG was recorded extracellularly with a glass-insulated silver wire
      microelectrode. When the unilateral VA was occluded for 5 min. the spontaneous
      firing rate in the MVN was altered as follows. The type A pattern exhibited a
      transient increase, followed by a decrease. The type B pattern showed a gradual
      decrease, and no further changes after the onset of occlusion. Type A and B
      patterns were observed respectively in MVN ipsi- and contra-lateral to the VA
      occlusion. In contrast, the VG neuronal firing rate was not affected by the
      occlusion. These results seem to support the clinical suggestion that the vertigo
      in VBI is produced by a difference in the function between the bilateral
      vestibular nuclei. rather than by the peripheral vestibular nerve.

PMID- 9657308
TI  - Hemodynamics of a simulation of the vertebrobasilar system using silicone tube.
AB  - We investigated the hemodynamics of the vertebrobasilar system (VBS) using a
      simulation model tube made of silicone which had different diameters between the
      bilateral vertebral artery (VA) ducts (stenotic and normal VA ducts). Using the
      ultrasonic Doppler method. the laterality index (L.I.) of the flow velocity in
      the VA duct was 32.88%. The flow volume of the anterior inferior cerebellar
      artery duct and the posterior inferior cerebellar artery duct also had
      significant laterality. By investigating the effects of the rotatory pulse rate
      and fluid viscosity, a maximal decrease to below 40-50% of the flow volume of the
      branches, and to below 71.93% in the mean flow velocity of the basilar artery
      (BA) duct (BA duct) were observed. and the maximum L.I. increased to 43.15%. When
      the unilateral stenotic VA duct was occluded by clamping (clamping occlusion),
      the flow volume profiles of the branches were the same as without clamping
      occlusion. The L.I. showed no significant changes and the maximal decrease in the
      mean flow velocity of the BA duct was 68.61%. Using the laser Doppler method, the
      flow velocity distribution of the BA duct was shifted towards the side of the
      stenotic VA duct. These results suggest that the rheological dynamics in the main
      vessels can certainly reflect the posterior circulatory dynamics, and that
      modulating factors also aggravate the hemodynamics of the VBS with this disorder.

PMID- 9657309
TI  - Inner ear blood flow in the rat after unilateral arterial occlusion in the
      vertebrobasilar arterial system.
AB  - It is generally accepted that certain kinds of vertigo and hearing disturbances
      are caused by blood flow insufficiency in the vertebrobasilar arterial system.
      Using the microsphere method we investigated whether unilateral vertebral artery
      or unilateral posterior inferior cerebellar artery occlusion could cause an
      imbalance between right and left inner ear blood flow in rats. We also studied
      the differential vulnerability between blood flow in the cochlea and in the
      ampullae of the three semicircular canals. We counted the numbers of microspheres
      distributed to the cochlea (CO) and microspheres distributed to three ampullae of
      semicircular canals (SC) under a microscope with the surface preparation method.
      The results were as follows: i) no imbalances were observed between bilateral CO
      or SC even in animals with arterial occlusion, and ii) the CO/SCs of animals with
      arterial occlusion were not significantly different from that of the control
      animals. These findings suggest that total inner ear blood flow over a certain
      period of time was even between the ears bilaterally even in animals with
      arterial occlusion. The blood flow in the ampullae of the three semicircular
      canals was not more or less affected by arterial occlusion than the blood flow in
      the cochlea.

PMID- 9657310
TI  - Influence of hyperlipidemia and smoking on age-related changes in caloric
      response and pure-tone hearing.
AB  - To examine the influence of hyperlipidemia and smoking on age-related changes in
      caloric response and pure-tone hearing, a caloric test and pure-tone audiometry
      were performed in 14 healthy volunteers and in 78 tinnitus patients without
      subjective hearing loss. The patients were from 24 to 84 years of age, and were
      divided into 4 groups: the no-risk group (N group), the smoking alone group (S
      group), the hyperlipidemia alone group (L group), and the smoking plus
      hyperlipidemia group (S-L group). Slow phase eye velocity of the caloric
      nystagmus (SPEV) and average hearing level at high frequencies were compared
      between the N groups and the other groups. There was a significant difference in
      SPEV only between the N and S-L groups, but not in the hearing level. This
      suggests that age-related changes in the caloric response be promoted by
      atherosclerosis, unlike presbycusis.

PMID- 9657311
TI  - Four cases of vertebrobasilar insufficiency.
AB  - Four cases of vertebrobasilar insufficiency are reported. Case 1 was a 38-year
      old man who felt a sudden onset of dizziness when he turned his head to the back.
      An abnormal positional nystagmus was observed when he rotated his head to the
      left. A magnetic resonance angiogram (MRA) demonstrated total occlusion of the
      left vertebral artery (VA). Case 2 was a 31-year-old woman who had a total
      occlusion of her left VA as observed in the MRA. Case 3 was a 68-year-old man who
      noted dizziness. The systolic blood pressure change on his Schellong test was 28
      mmHg. On his MRA, severe displacement of the basilar and the vertebral arteries
      was visible. Case 4 was a 76-year-old woman who noted a blackout-like sensation.
      Optokinetic nystagmus was noted with a hyponystagmus pattern, and an eye tracking
      test showed a saccadic pattern. On her MRA, the vertebrobasilar system was
      narrowed. The arterial architecture and any stenosis of the blood vessels could
      be detected non-invasively by MRA.

PMID- 9657312
TI  - MR-angiographic findings of patients with central vestibular disorders.
AB  - Magnetic resonance angiography (MRA) is a new, noninvasive, and useful method to
      estimate the posterior circulation in patients with vertigo. From June 1995 to
      May 1997, 180 patients were examined by magnetic resonance imaging (MRI) and MRA
      in our department. One hundred and forty-seven patients were vertiginous
      patients. We measured the displacement angle of the basilar artery with MRA, and
      examined the relationship between the findings from some neurological
      examinations and MRA findings in patients with vertigo and dizziness. One hundred
      and forty-seven patients with vertigo or dizziness were examined by MRI and MRA.
      They were diagnosed with MRI images in addition to several neurological
      examinations. MRA was not used for the diagnosis but rather for measuring the
      displacement angle of the basilar artery. Eighty-six cases with central
      vestibular disorders, 11 cases with vertebrobasilar insufficiency, and 26 cases
      with autonomic nerve disorders were recognized. In the cases of central
      vestibular disorders, the incidences of hyperlipidemia and hypotension were
      higher than the incidence of anemia. The average displacement angle of the
      basilar artery (n = 180) was 153.4 degrees +/- 39.4 degrees (mean +/- S.D.). MRA
      findings were classified into five categories. Ten patients were classified as
      category III, which represented unilateral partial vertebral artery stenosis. The
      detection rate for category III and IV abnormalities by neurological examination
      was higher than that for the other categories. MRI and MRA are important methods
      to examine patients with central nervous disorders. Distal vertebral artery
      stenosis may carry a higher risk of a stroke than brainstem infarction.

PMID- 9657313
TI  - Magnetic resonance imaging (MRI) test in hemodynamic vertebro-basilar
      insufficiency.
AB  - We investigated the efficiency of analysis by magnetic resonance imaging (MRI) in
      cases of hemodynamic vertebro-basilar insufficiency (VBI). We enrolled 76 cases
      of hemodynamic VBI who had visited our clinic in the Department of
      Otolaryngology, Nara Medical University, from 1994 to 1996. The evaluation of MRI
      was classified according to the degree of ventricular dilatation, callosal
      degeneration, and lacunar infarction, and the evaluation of MR angiography (MRA)
      was classified according to the degree of pathological change of the blood
      vessels. There was a significant difference in lacunar infarction on the MRI
      findings between VBI cases and normal controls, and there were also significant
      differences in side differences in the vertebral artery between VBI cases and
      peripheral vertigo and normal control patients. We propose an etiology for
      hemodynamic VBI: a functional cerebral circulation disorder causes ischemia of
      the basal ganglia and leads to lacunar infarctions; furthermore, the side
      difference between the two vertebral arteries causes a circulation disorder in
      the vertebrobasilar system.

PMID- 9657314
TI  - Radiation-induced cancers of the head and neck region.
AB  - A total of 65 patients with radiation-induced cancers of the head and neck region
      were treated and evaluated. The primary disease for which the radiotherapy had
      been applied was benign disease in 48 patients (including tuberculous
      lymphadenitis in 39 patients), and malignant tumors in 17 patients (including 9
      laryngeal cancers and 5 thyroid cancers). The radiation-induced cancers included
      35 cases of hypopharyngeal cancer, 15 of thyroid cancer, and 13 of cervical
      esophageal cancer. The mean duration from radiotherapy until the diagnosis of
      cancer was 12.8 years in the patients with malignant primary tumor and 32.9 years
      in those with benign primary diseases. Most of the patients underwent surgery for
      their cancer. The clinical course was poor and the outcome extremely poor,
      especially in those patients with field carcinogenesis. It is emphasized that
      excessively high dosage and wide radiation field should be avoided, and that
      radiotherapy for young patients with malignancies requires extremely careful
      management.

PMID- 9657315
TI  - Structure of the O-specific polysaccharide of Proteus penneri strain 41 from a
      new proposed serogroup O62.
AB  - O-specific polysaccharide of Proteus penneri strain 41 was studied using 1H- and
      13C-NMR spectroscopy, including two-dimensional COSY, heteronuclear 13C,1H
      correlation (HETCOR) and one-dimensional NOE spectroscopy, and the following
      structure of a non-stoichiometrically O-acetylated hexasaccharide repeating unit
      was established:[structure: see text] where RGlcNAc is 2-acetamido-4-O-[(S)-1
      carboxyethyl]-2-deoxyglucose. Cross-reactivity of anti-P. penneri 41 O-serum with
      other P. penneri strains is discussed, and a new, separate O62 serogroup is
      proposed which is the next Proteus O-serogroup containing P. penneri strains
      only.

PMID- 9657316
TI  - Rhodococcus equi infection of monocytes/macrophages from human immunodeficiency
      virus (HIV)-infected patients and healthy individuals: evaluation of
      intracellular killing and nitric oxide production.
AB  - Monocytes/macrophages from human immunodeficiency virus (HIV)-infected patients
      had a defect in their ability to kill Rhodococeus equi in vitro, as compared with
      healthy HIV-seronegative individuals. Virulent and avirulent R. equi strains
      isolated from humans and horses showed no significant intracellular replicative
      differences within both HIV-positive and -negative monocytes/macrophages.
      Infection with R. equi induced the production of nitric oxide (NO) by
      monocytes/macrophages from healthy individuals, but not by cells from HIV
      positive patients. The NO formation was significantly inhibited by L-NG
      monomethyl arginine and arginase. However. neither competitive inhibition of NO
      synthesis from L-arginine with L-NMMA nor depletion of arginine with arginase
      altered the killing activity of human monocytes/macrophages against R. equi, thus
      suggesting that L-arginine:NO pathway is not required for the intracellular
      antirhodococcal mechanisms of human monocytes/macrophages.

PMID- 9657318
TI  - Evaluation of the antimicrobial effect of lactoferrin on Porphyromonas
      gingivalis, Prevotella intermedia and Prevotella nigrescens.
AB  - The antimicrobial effect of lactoferrin (apoLf) on the oral, black-pigmented
      anaerobes Porphyromonas gingivalis, Prevotella intermedia and P. nitrescens has
      been studied. ApoLf did not kill any of these species but it did inhibit the
      growth of P. gingivalis, while iron-saturated Lf (FeLf) had no effect. The other
      two species were unaffected by apoLf. This growth inhibitory effect of apoLf
      could not be explained on the basis of chelation of inorganic iron, since growth
      of P. gingivalis occurred in the presence of ethylenediamine di-o
      hydroxyphenylacetic acid provided haemin was added. Both apoLf and FeLf reduced
      haemin uptake by all three species and caused the release of cell-bound haemin in
      a dose-dependent manner. In addition, haemin reduced the binding of both apoLf
      and FeLf to P. intermedia and P. nigrescens but stimulated the binding of Lf by
      P. gingivalis. These data suggest that Lf forms complexes with haemin in solution
      and competes for the binding of haemin to certain cell receptors, possibly
      lipopolysaccharides, but this is not sufficient to inhibit growth of the
      bacteria. P. gingivalis appears to bind Lf-haemin complexes, as well as haemin
      alone, which may facilitate access of the Lf to the outer and cytoplasmic
      membranes of P. gingivalis, so disrupting function.

PMID- 9657317
TI  - Protective efficacy of mycobacterial 71-kDa cell wall associated protein using
      poly (DL-lactide-co-glycolide) microparticles as carrier vehicles.
AB  - Microparticles composed of poly (DL-lactide-co-glycolide) (DL-PLG) were used as
      delivery vehicles for evaluating the immunoreactive and immunoprotective
      properties of 71-kDa cell wall associated protein of Mycobacterium tuberculosis
      H37Ra. Mice immunized with 71-kDa microparticles entrapped in DL-PLG (PLG-MPs)
      exhibited significantly higher T-cell stimulation and cytokine release in
      comparison to 71-kDa emulsified in Freund's incomplete adjuvant (FIA) as well as
      a BCG vaccinated group throughout the post-immunization (p.im.) period. Further,
      the protective efficacy of 71-kDa was evaluated on the basis of survival rates
      and viable bacilli load in different organs at 30 days post challenge (p.c.),
      with the median lethal dose (LD50) of M. tuberculosis H37Rv at weeks 8 and 16
      p.im. Both 71-kDa-PLG and 71-kDa-FIA immunized groups exhibited a comparable
      protection (90%) which was significantly higher (P < 0.5) than in the BCG group
      (70%) at week 8 p.im. and it was consistent with the decreased bacterial load in
      the target organs. However, on increasing the interval of challenge to 16 weeks
      p.im., the protective efficacy of 71-kDa-PLG was sustained (85%) while that of 71
      kDa-FIA began to wane (70%). Further. the 71-kDa-PLG immunized group exhibited a
      significantly higher (P < 0.001) clearance of bacterial load from the lungs and
      livers in comparison to the 71-kDa-FIA immunized group. The results suggest the
      long-term protective potential of a PLG-microparticle based antigen delivery
      system for tuberculosis.

PMID- 9657319
TI  - Altered expression of constitutive type and inducible type heat shock proteins in
      response of D-galactosamine-sensitized mice to lipopolysaccharide as an
      experimental endotoxic shock model.
AB  - The expression of heat shock proteins (HSPs) as stress-induced proteins was
      studied in mice injected with D-galactosamine (D-GalN) and lipopolysaccharide
      (LPS) as an experimental endotoxic shock model. The expression of constitutive
      type heat shock protein 70 (HSC70) was significantly reduced in livers of mice
      injected with D-galactosamine and lipopolysaccharide, while its expression was
      unaffected in livers of mice injected with D-galactosamine or lipopolysaccharide
      alone. The expression of other constitutive type heat shock proteins, namely
      HSP60, HSP32 and HSP25 was also reduced in mice injected with D-galactosamine and
      lipopolysaccharide. On the other hand, inducible type HSP70 was detected in
      livers from mice injected with D-galactosamine and lipopolysaccharide, but not in
      livers from mice injected with D-galactosamine or lipopolysaccharide alone.
      Simultaneous injection of anti-tumor necrosis factor (TNF)-alpha antibody
      prevented the liver from reduced expression of constitutive type HSC70, and lead
      to marked expression of inducible type HSP70 in the liver. Reduced expression of
      constitutive type HSC70 was also found when D-galactosamine and recombinant TNF
      alpha was injected. Therefore, TNF-alpha was suggested to play a critical role on
      altered expression of constitutive HSC70 and inducible type HSP70 in response of
      D-galactosamine-sensitized mice to lipopolysaccharide.

PMID- 9657320
TI  - Rare, suppurative pulmonary infection caused by Nocardiopsis dassonvillei
      recognized by glycolipid markers.
AB  - An opportunistic actinomycete was isolated as the only etiological agent of a
      severe, suppurative pulmonary infection. The strain was rapidly recognised as
      Nocardiopsis by the taxonomically important and immunologically active glycolipid
      markers (G1 and G2). Identification of the clinical isolate, from a group of
      actinomycetes mainly known as soil habitants, was definitely proved by
      chemotaxonomic studies (cell wall/sugar, phospholipid and fatty acid types) as
      well as by genomic data (GC content, DNA-DNA reassociation). The level of DNA-DNA
      homology of the clinical actinomycete, in comparison with other reference members
      of this genus, revealed the highest (88%) relatedness to Nocardiopsis
      dassonvillei. The results confirmed the value and generic specificity of
      glycolipid markers from Nocardiopsis, the first time used for rapid recognition
      of a clinical strain causing a nocardiosis-like disease.

PMID- 9657321
TI  - Phospholipid molecular species distribution of oral Prevotella corporis clinical
      isolates.
AB  - The aim of this study was to determine the distribution of phospholipid molecular
      species within Prevotella corporis of oral origin. Phospholipids of fresh
      clinical isolates were extracted and analysed by fast atom bombardment mass
      spectrometry (FAB-MS) in negative-ion mode. The major monocarboxylate anion
      peaks, with putative identification, observed for Prevotella corporis were m/z
      241, C(15:0); 255, C(16:0); 269, C(17:1); 277, C(18:3); 279, C(18:2); 281,
      C(18:1). In the high mass region, major anion peaks putatively identified as
      individual phospholipid (PL) molecular species of Prevotella corporis were of m/z
      677, PG(29:1); 691, PG(30:1); 705, PG(31:1); 706, first isotope peak of PG(31:1);
      and 707, PG(31:0). Related species have a different distribution of PL analogues.
      Separation of extracted lipid families by TLC confirmed that
      phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) are the major polar
      lipids (PLs) in Prevotella corporis. Thus Prevotella corporis has a unique
      combination of phospholipid analogues of chemosystematic significance.

PMID- 9657322
TI  - Psoriasis patients have T-cells with reduced responsiveness to common
      mycobacterial antigens.
AB  - Heparinised blood samples were obtained from 20 patients with chronic plaque
      psoriasis and from 13 age-matched healthy controls. After preliminary titration,
      mononuclear cells separated over Ficoll-Tryoson were cultured for 5 days with 10
      microg ml(-1) of 15 mycobacterial preparations, or with pokeweed mitogen and
      concanavalin A. Stimulation indices were determined for each reagent and means
      were determined for patients and controls. Results for patients showed a striking
      reduction of responsiveness to mycobacteria, apparently due to loss of responses
      to group i, common mycobacterial antigens, and no differences in responses to
      mitogens. These observations relate psoriasis to certain other diseases, notably
      mycobacterial infections, rheumatoid arthritis, Chagas' disease and human
      immunodeficiency virus infection. The observations may be relevant to the
      aetiology of psoriasis, and to potential immunotherapy for the disease.

PMID- 9657323
TI  - Immunotherapy with Mycobacterium vaccae in the treatment of psoriasis.
AB  - A placebo-controlled study of immunotherapy with Mycobacterium vaccae for chronic
      plaque psoriasis showed improvement in the psoriasis area severity index in 19 of
      21 immunotherapy recipients (P<0.005). Minor improvement, not reaching
      statistical significance for the group, occurred in nine of 14 placebo
      recipients. There were losses to follow-up and the placebo used, tetanus toxoid,
      was not ideal. Clinical improvement after immunotherapy persisted for 6 months
      and another injection of the immunotherapeutic given to a few volunteers from
      either group resulted in benefits lasting a year. Lymphoproliferative tests were
      carried out at each clinic visit, and on 50 matched controls. Starting with
      reduced responses to mycobacterial antigens and concanavalin A, both treatment
      groups showed a fall after 3 months, and diverged at 6 months with M. vaccae
      recipients rising to values similar to those of healthy controls, whereas placebo
      recipients continued to fall. Conclusions reached were that immunotherapy with M.
      vaccae gave long-lasting clinical benefit to most patients, with minimal side
      effects. This accompanied a return towards normal cellular immune responsiveness
      to mycobacterial antigens, which did not follow the use of the placebo.

PMID- 9657324
TI  - Effect of O-antigenic polysaccharide of Escherichia coli on endotoxin
      neutralizing activity of lysozyme.
AB  - Endotoxemia is considered to be associated with the high mortality of gram
      negative septic patients. Increasing evidence shows that beta-lactam antibiotics
      have a propensity to induce endotoxin release from the bacterial outer membrane
      while killing bacteria. We have recently found that egg white lysozyme (EW-LZM)
      shows strong inhibition of beta-lactam induced bacteriolysis and
      lipopolysaccharide (LPS) release from Escherichia coli O111, resulting in
      reduction of the LPS-initiated inflammatory response. In this study, we compared
      the effect of EW-LZM on E. coli J5, which possesses rough-type LPS (RaLPS), in
      order to demonstrate the effect of O-antigenic polysaccharide on endotoxin
      neutralizing activity of EW-LZM and on inhibition of beta-lactam induced lysis by
      LZM. Both of the beta-lactam induced bacterial lysis and subsequent LPS release
      were almost completely inhibited by EW-LZM. The effect was more potent than that
      of wild-type LPS as assessed by released LPS concentration and LPS induced
      cytokine syntheses. In addition, EW-LZM was effective against lethal infection of
      E. coli J5 in cyclophosphamide induced leukopenic mice. These facts strongly
      suggested that O-antigenic polysaccharide negatively modulates LPS neutralizing
      activity of EW-LZM.

PMID- 9657325
TI  - Isolation, characterization and disruption of the casein kinase II alpha subunit
      gene of Leishmania chagasi.
AB  - To elucidate the role played by casein kinase II in Leishmania survival, we have
      isolated and characterized the Leishmania chagasi casein kinase II alpha subunit
      cDNA, (L.c CKIIalpha). The 1083 bp coding region is flanked by 148 bp of 5' UTR
      and 1155 bp of 3' UTR. L.c CKIIalpha shows a remarkable degree of similarity with
      other isolated casein kinase II alpha subunit sequences. L.c CKIIalpha protein is
      encoded by a single copy gene that transcribes a mRNA of 2.4 kb. The 41.2 kDa L.c
      CKIIalpha protein expressed in vitro has been shown to be catalytically active. A
      single allele disruption of the L.c CKIIalpha gene that removes 94 bp from the
      coding region which contains one of the 15 conserved amino acids closest to the
      carboxy-terminus of the protein has been generated. This mutant is viable and
      results in a reduction of L.c CKIIalpha transcript levels over 14-fold and that
      of an iron superoxide dismutase mRNA by 5-fold. As well, the kinase activity of
      the single allele disrupted cells showed a 3-fold reduction as compared to the
      wild type cells suggesting a decrease in activity of the L.c CkIIalpha enzyme.

PMID- 9657326
TI  - Nuclear antigens in Trichinella spiralis infected muscle cells: nuclear
      extraction, compartmentalization and complex formation.
AB  - Infection of mammalian skeletal muscle cells by Trichinella spiralis induces a
      series of changes that include: reentry of the terminally differentiated host
      cell into the cell cycle; suspension of infected cells in apparent G2/M; and
      transcriptional inactivation of the differentiated skeletal muscle gene program.
      Cell cycle repositioning and genetic reprogramming are chronic characteristics of
      host cells that can remain infected for years. Nuclear antigens (NA, 79, 86 and
      97 kDa) that localize to host cell nuclei have been detected with antibodies
      against T. spiralis proteins. Since NA may play a role in regulating the infected
      cell phenotype, their origin, nuclear compartmentalization, and biochemical
      properties were investigated. We show that a monoclonal antibody to a defined
      epitope of T. spiralis glycans binds these NA, which indicates the parasite
      origin of these proteins. NA were not extracted under conditions that solubilized
      chromatin from infected cell nuclei. In contrast, NA were coextracted with B
      lamins (nuclear envelope) by 4 M urea. Urea extraction was pH dependent (8.0),
      suggesting ionic interaction of NA in protein complexes. Nevertheless, confocal
      microscopy demonstrated colocalization of NA with host chromatin, and not B
      lamins. Nuclear protein complexes containing NA were observed under non-reducing
      conditions, and NA were readily cross-linked in isolated nuclei by succinimidyl
      protein conjugating reagents. The results establish methods to extract NA from
      infected cell nuclei for further biochemical analysis, establish the existence of
      nuclear protein complexes containing NA and demonstrate colocalization of NA with
      host chromatin. Collectively, the results provide a foundation from which to
      investigate the role of NA in regulating the T. spiralis infected skeletal muscle
      cell phenotype.

PMID- 9657327
TI  - Relation between variation in copy number of ribosomal RNA encoding genes and
      size of harbouring chromosomes in Leishmania of subgenus Viannia.
AB  - Chromosomal size polymorphism in Leishmania of subgenus Viannia has been
      correlated with eco-geography. The sizes of chromosomes bearing rDNA genes were
      determined in 69 isolates. A considerable size-variation was observed, ranging
      from 1100 to 1500 kb. Chromosomes of L.(V.). braziliensis, L.(V.)guyanensis and
      L.(V.) peruviana from northern Peru were significantly larger (200 kb) than those
      of L.(V.) peruviana from southern Peru. In addition, 31 out of 69 isolates
      presented each two different-sized homologues of the rDNA chromosome. Long range
      restriction mapping of three different-sized rDNA chromosomes from
      L.(V.)braziliensis M2903 and L.(V.)peruviana HB31 (north) and LC106 (south) each
      revealed three fragments delimited by PmeI restriction sites: two constant in
      size (the centre and one extremity of the chromosome) and one variable (the other
      extremity, containing a single cluster of rDNA genes). Further analysis of the
      M2903 rDNA chromosome allowed the localization of its 140 kb rDNA cluster at 85
      kb from the telomeric end. Two arguments indicated that size-variation of the
      rDNA chromosome is partially due to amplification/deletion of the clustered rDNA
      genes: (i) size-variation of the cluster-containing fragment was proportional to
      the size-variation of the whole chromosome, and (ii) hybridization signal
      intensity of the rDNA chromosome with a small subunit rDNA probe strongly
      correlated with chromosomal size. Nevertheless, DNA sequences present between the
      rDNA cluster and the telomere might also play a role in chromosomal size
      polymorphism. In addition, our data suggest that rDNA gene copy number (20-40
      copies cell(-1) under a diploid hypothesis) in subgenus Viannia is lower than
      reported previously.

PMID- 9657328
TI  - Upstream elements required for expression of nucleoside triphosphate hydrolase
      genes of Toxoplasma gondii.
AB  - Nucleoside triphosphate hydrolase is an abundant protein secreted by the obligate
      protozoan parasite Toxoplasma gondii. The protein has apyrase activity, degrading
      ATP to the di- and mono-phosphate forms. Because T. gondii is incapable of de
      novo synthesis of purines, it is postulated that NTPase may be used by the
      parasite to salvage purines from the host cell for survival and replication. To
      elucidate the molecular mechanisms of NTP gene expression, we isolated from the
      virulent RH strain of T. gondii the putative promoter region of three tandemly
      repeated NTP genes (NTP1, 2, 3). Using deletion constructs linked to the
      chloramphenicol acetyl transferase (CAT) reporter gene, we defined an active
      promoter within the first 220 bp. Sequence analysis of this region reveals the
      lack of a TATA box, but the promoter region is associated with a sequence which
      resembles an initiator element (Inr) in the NTP1 and NTP3 genes. This sequence
      which is similar to other Inrs known to regulate the expression of a wide variety
      of RNA polymerase II genes, is required for NTP expression. The NTP3 promoter
      contains sufficient information for developmentally regulated expression of CAT
      activity when the actively replicating stage tachyzoite differentiates into the
      dormant bradyzoite form.

PMID- 9657329
TI  - Predicted and observed alleles of Plasmodium falciparum merozoite surface protein
      1 (MSP-1), a potential malaria vaccine antigen.
AB  - The 19-kDa antigenic domain of Plasmodium falciparum merozoite surface protein
      (MSP)-1 is a potential malaria vaccine candidate. Based on the amino acid
      substitution, four known alleles, E-TSR (PNG-MAD20 type), E-KNG (Uganda-PA type),
      Q-KNG (Wellcome type), and Q-TSR (Indo type) of this domain have been identified.
      Using single or double crossover recombinational events, we predicted the
      existence of additional alleles of this antigen. The presence of the predicted
      alleles was determined in parasite isolates from western Kenya, by undertaking a
      cross-sectional and a longitudinal study. Of the ten predicted alleles, we have
      revealed the presence of three new alleles: E-KSG-L (Kenya-1 type); E-KSR-L
      (Kenya-2 type); and E-KNG-F (Kenya-3 type). The results of this study suggest
      that it may be possible to predict the complexity of the genetic makeup of
      natural parasite populations.

PMID- 9657330
TI  - A phylogenetic analysis of the Trypanosoma cruzi genome project CL Brener
      reference strain by multilocus enzyme electrophoresis and multiprimer random
      amplified polymorphic DNA fingerprinting.
AB  - We have assessed the phylogenetic status of the Trypanosoma cruzi Genome Project
      CL Brener reference strain by multilocus enzyme electrophoresis (MLEE) and
      multiprimer random amplified polymorphic DNA (RAPD) including a set of cloned
      stocks representative of the whole genetic diversity of T. cruzi. MLEE and RAPD
      data gave congruent phylogenetic results. The CL Brener reference strain fell
      into the second major phylogenetic subdivision of T. cruzi, and was genetically
      very close to the Tulahuen reference strain. No reliable RAPD character and only
      one MLEE character permitted us to distinguish between the CL Brener and Tulahuen
      reference strains. In contrast, many RAPD and MLEE characters were able to
      distinguish between the CL Brener reference strain and the other T. cruzi
      genotypes analyzed here, in particular the formerly described principal zymodemes
      I, II and III. It is suspected that both CL Brener and Tulahuen are hybrid
      genotypes, a fact that should be taken into account when interpreting sequence
      data. Moreover, our study confirms that the species T. cruzi is genetically very
      heterogeneous. We recommend future comparison of sequencing data from the CL
      Brener reference strain with those of at least one radically distinct T. cruzi
      genotype, belonging to the other major phylogenetic subdivision of this species.

PMID- 9657331
TI  - Sequence variations in the Plasmodium vivax dihydrofolate reductase-thymidylate
      synthase gene and their relationship with pyrimethamine resistance.
AB  - The gene encoding dihydrofolate reductase-thymidylate synthase of the human
      malaria parasite, Plasmodium vivax, was isolated by polymerase chain reaction
      from genomic DNA and cloned. The sequences of the dihydrofolate reductase domain
      of 30 clinical isolates originating from various geographic areas were compared.
      Interstrain analysis revealed several genotypic variations, including short
      tandem repeat arrays which produced length polymorphism between different
      parasite isolates and point mutations in the putative dihydrofolate reductase
      active site cavity corresponding to those associated with pyrimethamine
      resistance in P. falciparum and rodent malaria parasites. Amino acid
      substitutions Ser-->Asn-117 and Ser-->Arg-58 were associated with decreased level
      of in vitro pyrimethamine sensitivity. These findings suggest that the P. vivax
      dihydrofolate reductase domain is characterized by polymorphism that has not been
      observed in P. falciparum and may explain the resistance of some P. vivax
      isolates to pyrimethamine. Nucleotide sequence data reported in this paper are
      available in the EMBL, GenBank and DDJB databases under the accession numbers
      X98123 (isolate ARI/Pakistan), AJ003050 (isolate CNC/Thailand), AJ003051 (isolate
      COU/unknown geographic origin), AJ003052 (isolate DUF/French Guiana), AJ003053
      (isolate GRO/Madagascar), AJ003054 (isolate HRT/Comoros Islands), AJ003071
      (isolate LFT/Cambodia), AJ003072 (isolate LGF/'India), AJ003073 (isolate
      MAN/Comoros Islands), AJ003074 (isolate MAT/Surinam), AJ003075 (isolate
      PHI/Djibouti), AJ003076 (isolate PIT/Madagascar), AJ003077 (isolate
      YTZ/Indonesia), AJ222630 (isolate Burma-1), AJ222631 (isolate Burma-151),
      AJ222632 (isolate Burma-5), AJ222633 (isolate Burma-6), AJ222634 (isolate Burma
      98).

PMID- 9657332
TI  - Characterisation of Tc-cpl-1, a cathepsin L-like cysteine protease from Toxocara
      canis infective larvae.
AB  - Cysteine proteases play vital biological roles in both intracellular and
      extracellular environments. A cysteine protease migrating at 30 kDa was
      identified in somatic extracts of Toxocara canis larvae (TEX), by its binding to
      the biotinylated inhibitor Phe-Ala-CH2F. TEX proteases readily cleaved the
      cathepsin L- and B-specific peptide substrate Z-Phe-Arg-AMC and to a lesser
      extent, the cathepsin B-specific peptide Z-Arg-Arg-AMC. Excretory/secretory (TES)
      products of T. canis larvae did not cleave either substrate. Partial sequence
      encoding the 5' end of a cysteine protease cDNA from infective T. canis larvae
      was then obtained from an expressed sequence tag (EST) project. The entire cDNA
      (termed Tc-cpl-1) was subsequently sequenced and found to encode a preproenzyme
      similar to cathepsin L-like proteases (identities between 36 and 69%), the
      closest homologues being two predicted proteins from Caenorhabditis elegans
      cosmids, a cathepsin L-like enzyme from Brugia pahangi and a range of parasite
      and plant papain-like proteases. Sequence alignment with homologues of known
      secondary structure indicated several charged residues in the S1 and S2 subsites
      involved in determining substrate specificity. Some of these are shared with
      human cathepsin B, including Glu 205 (papain numbering), known to permit cleavage
      of Arg-Arg peptide bonds. The recombinant protease (rTc-CPL-1) was expressed in
      bacteria for immunisation of mice and the subsequent antiserum shown to
      specifically react with the 30 kDa native protease in TEX. Sera from mice
      infected with the parasite also contained antibodies to rTc-CPL-1 as did sera
      from nine patients with proven toxocariasis; control sera did not. Larger scale
      studies are underway to investigate the efficacy of rTc-CPL-1 as a diagnostic
      antigen for human toxocariasis, the current test for which relies on whole
      excretory/secretory antigens of cultured parasites.

PMID- 9657333
TI  - Targeted disruption of the bradyzoite-specific gene BAG1 does not prevent tissue
      cyst formation in Toxoplasma gondii.
AB  - Expression of the 30 kDa small heat shock protein BAG1 is restricted to the
      latent bradyzoite 'tissue cyst' form of Toxoplasma gondii, first appearing
      approximately 2-3 days after the initiation of bradyzoite differentiation.
      Although developmental expression of small heat shock proteins has been described
      for many species, their precise function is unclear. In order to examine the
      function of BAG1 in T. gondii bradyzoites and its role during parasite
      differentiation, we have used homologous recombination to produce a knock-out
      mutant in the cyst-forming strain P(LK), a clonal derivative of ME49. Under
      tissue culture conditions that stimulate bradyzoite differentiation (alkaline
      pH), the mutant was found to express several bradyzoite-specific markers with the
      same kinetics and frequency as the parental strain. Neither enhanced nor
      decreased susceptibility to stress was observed for the BAG1-deficient mutant. In
      vivo studies revealed that tachyzoites of the bag1 knock-out mutant were fully
      able to establish a chronic infection in C57BL/6 mice, producing brain cysts of a
      size, morphology and frequency indistinguishable from cysts formed by the
      parental control strain. Brain cysts of the bag1 knock-out mutant contained
      viable parasites capable of establishing an acute infection after oral
      administration, demonstrating that conversion of bradyzoites to tachyzoites is
      also unimpaired. We conclude that BAG1 is not essential for normal function of
      bradyzoite containing tissue cysts, at least in intermediate host species. This
      clone of P(LK) was found to be unable to produce oocysts and is therefore
      unsuitable for studies in cats.

PMID- 9657334
TI  - A mutation scanning approach for the identification of hookworm species and
      analysis of population variation.
AB  - To overcome limitations in the morphological identification of different
      developmental stages of hookworms to species, we have established a polymerase
      chain reaction-linked single strand conformation polymorphism technique (PCR
      SSCP) utilizing the internal transcribed spacers (ITS) of ribosomal (r)DNA. These
      spacers were specifically chosen because they provide reliable species markers
      for strongylid nematodes. ITS spacers were amplified by PCR from DNA derived from
      individual parasites of seven species of hookworm, then denatured and subjected
      to electrophoresis in a mutation detection enhancement (MDE) (non-denaturing) gel
      matrix. PCR SSCP analysis showed that the single-strand ITS patterns produced
      allowed the unequivocal identification of all species. The method also allowed
      the direct display of sequence variation within some species where multiple
      individual worms were examined. These findings demonstrate the usefulness of the
      SSCP approach for hookworm identification, the detection of population variation
      and the direct display of sequence variation in rDNA.

PMID- 9657335
TI  - Control mechanisms of the H2A genes expression in Trypanosoma cruzi.
AB  - In a previous report we have described that the T. cruzi histone H2A gene is
      encoded in two independent gene clusters located in a single chromosome. In the
      present paper we show that both gene cluster are actively transcribed as two
      sized classes of polyadenylated mRNAs demonstrating, moreover, the existence of
      alternative splicing sites and microheterogeneities at the polyadenylation site.
      We also describe that while the expression of the H2A genes in the non
      replicative trypomastigote forms is only residual, in the replicative forms there
      is constitutive transcription of these genes and that the transcription is not
      associated to DNA replication. The data show, moreover, that in the replicative
      forms the steady state levels of the H2A mRNAs are controlled at a post
      transcriptional level which is associated to DNA replication.

PMID- 9657336
TI  - Expression, selection, and organellar targeting of the green fluorescent protein
      in Toxoplasma gondii.
AB  - We have engineered a mutant version of the green fluorescent protein GFP (Cormack
      et al. Selected for bright fluorescence in E. coli. Gene 1996;173:33-38) for
      expression in the protozoan parasite Toxoplasma gondii. Although intact GFP was
      not expressed at any detectable level, GFP fusion proteins could be detected by
      fluorescence microscopy, flow cytometry (FACS), and immunoblotting. Both
      extracellular tachyzoites and T. gondii-infected host cells could readily be
      sorted by FACS, which should facilitate a variety of selection strategies.
      Several selectable markers were tested for their ability to produce stable green
      transgenic parasites. Fluorescence intensity was directly correlated with gene
      copy number and protein expression level. Weak selectable markers such as
      chloramphenicol acetyl transferase (CAT) driven by the SAG1 promoter, which yield
      multicopy insertions, are therefore most effective for selecting green
      fluorescent parasites-particularly when coupled to constructs which employ a
      strong promoter to drive GFP expression. Transformation vectors developed in the
      course of this work should be of general utility for the overexpression of
      heterologous transgenes in Toxoplasma. CAT-GFP fusion proteins were expressed in
      the parasite cytoplasm. GFP fusions to the P30 major surface antigen (linked on
      the same plasmid to a CAT selectable marker under control of various promoters)
      could be detected in dense granules within living cells, and were efficiently
      secreted into the parasitophorous vacuole. GFP fusions to the rhoptry protein
      ROP1 were targeted to rhoptries (specialized secretory organelles at the apical
      end of the parasite).

PMID- 9657337
TI  - Ecto-protein tyrosine phosphatase activity in Trypanosoma cruzi infective stages.
AB  - Live T. cruzi trypomastigotes and amastigotes possess ecto-protein tyrosine
      phosphatase activity as indicated by the ability of intact cells to catalyze
      dephosphorylation of tyrosine phosphorylated myelin basic protein,
      [32P]TyrRaytide, phosphotyrosine, or the phosphotyrosine analog p
      nitrophenylphosphate (p-NPP). The dephosphorylation of myelin basic protein (MBP)
      and p-NPP was inhibited by sodium o-vanadate, zinc chloride and NaF, while
      dephosphorylation of [32P]TyrRaytide was insensitive to zinc chloride but
      sensitive to o-vanadate and NaF. In contrast, live cells were not able to
      dephosphorylate serine or threonine phosphorylated peptides ([32P]Kemptide) or
      proteins ([32P]RCM-lysozyme and [32P]MBP).

PMID- 9657338
TI  - Variation in the thrombospondin-related adhesive protein (TRAP) gene of
      Plasmodium falciparum from Thai field isolates.

PMID- 9657339
TI  - Cloning and expression of the Entamoeba histolytica ERD2 gene.

PMID- 9657340
TI  - Active site mutants of a cyclosporin A-insensitive cyclophilin from Brugia
      malayi: effect on catalysis and drug binding.

PMID- 9657341
TI  - Immunolocalization of Trypanosoma brucei hypoxanthine-guanine
      phosphoribosyltransferase to the glycosome.

PMID- 9657342
TI  - Follicle stimulating hormone international standards and reference preparations
      for the calibration of immunoassays and bioassays.
AB  - Follicle stimulating hormone is a dimeric glycoprotein hormone which is used
      widely in reproductive and developmental medicine both as a diagnostic analyte
      and as a therapeutic product. It is therefore a good example of a clinically
      important heterogeneous material for which a number of different assay
      methodologies have been developed. Immunoassays for follicle stimulating hormone
      (FSH) are used in the diagnosis of disorders of reproduction and development,
      whereas in vivo bioassays are used for calibration of therapeutic preparations.
      Different immunoassay systems, based on different formats, exhibit variability in
      their estimates of activity of FSH which arises from different specificities of
      antibodies for different forms of FSH which are encountered. In order to minimise
      between assay variation and to enable better between laboratory comparisons the
      World Health Organisation (WHO) has issued a series of ampouled preparations of
      FSH. The availability of these materials has been reviewed previously but on the
      completion of a recent collaborative study to evaluate candidate standards for
      rDNA-derived FSH and highly purified urinary FSH (urofollitropin) it is now
      appropriate to review the current status of these standards and to discuss the
      future of standardisation for FSH in particular and where appropriate to make
      reference to other materials.

PMID- 9657343
TI  - Qualitative bedside assay of increased human serum myoglobin by sandwich dot
      immunogold filtration for the diagnosis of acute myocardial infarction.
AB  - We isolated and purified myoglobin (MYO) from human fresh skeletal muscle and
      prepared monoclonal and polyclonal antibody from it. A sandwich dot-immunogold
      filtration assay (DIGFA) for the detection of MYO was developed by using affinity
      purified sheep anti-MYO antibody as the first antibody for coating nitrocellulose
      membranes (NCMs; the support) and colloidal gold labelled monoclonal antibody
      (H3) as the second antibody (an indicator). The test can be completed in 3 min
      without incubation or any equipment. A reddish dot, indicating positivity, is
      obvious to the naked eye. No interferences from bilirubin, hemoglobin, rheumatoid
      factors and lipid were found. In order to use undiluted serum, the detection
      limit was set at 100 microg of MYO/l. Concentrations up to 30,000 microg/l can be
      measured without getting a "hook" effect. Serum MYO levels in 53 patients with
      acute myocardial infarction (AMI), 100 healthy individuals, seven patients with
      chest pain but without myocardial ischemia and in 39 patients with renal
      insufficiency were measured simultaneously by DIGFA and enzyme-linked
      immunosorbent assay (ELISA). All serum samples from patients had MYO
      concentrations above 100 microg/l by ELISA and were positive by DIGFA. Serum
      creatinine values were related to MYO test results. Healthy individuals had MYO
      levels below 85 microg/l by ELISA and were negative by DIGFA.

PMID- 9657344
TI  - Specific determination of germ cell alkaline phosphatase for early diagnosis and
      monitoring of seminoma: performance and limitations of different analytical
      techniques.
AB  - Two-dimensional electrophoresis, ion-exchange chromatography and immunoassay were
      evaluated in order to improve the diagnostic specificity of the germ cell
      specific isoenzyme of alkaline phosphatase (GCAP) for the detection of seminoma.
      Assessment of GCAP is hampered by its structural heterogeneity and low serum
      concentration. The structural heterogeneity of GCAP from seminoma tissue could be
      clearly visualized by two-dimensional electrophoresis. We inferred that it
      depended on allelic amino acid substitutions, varying sialylation and
      differential cleavage of the membrane anchor. The allelic variability of GCAP
      affects the accuracy of immunological measurements. However, immunoassay was
      found to be the only technique sensitive enough to assess GCAP in serum. The
      elevated GCAP levels in 15% of healthy blood donors were shown to be correlated
      with smoking. Further studies clarifying how to interpret the values measured in
      smokers are prerequisite for the introduction of GCAP as a serum marker for
      seminoma. In the future, GCAP might be utilized for the detection of carcinoma in
      situ (CIS) cells in ejaculate. Assessment of the enhanced expression of cellular
      GCAP by CIS cells exfoliated into ejaculate could be a means for noninvasive,
      early diagnosis that presumably will not be hampered by the patient's smoking
      habits.

PMID- 9657345
TI  - A non ouabain-like inhibitor of the sodium pump in uremic plasma ultrafiltrates
      and urine from healthy subjects.
AB  - A non ouabain-like inhibitor of the sodium pump was separated from uremic plasma
      ultrafiltrates and normal urine. Under the same chromatographic conditions (C18
      column and a gradient of acetonitrile as eluant), ouabain was eluted in a
      fraction different from the inhibitor. Affinity chromatography based on the
      formation of a complex between Na,K-ATPase and the inhibitor achieved the
      differentiation ouabain. Without magnesium and sodium phosphate, ouabain could
      not bind to enzyme whereas the inhibitor did. A study of Na,K-ATPase enzyme
      kinetics showed the inhibitor was not competitive for K+, which further
      differentiates it from ouabain. It was uncompetitive for ATP and seemed
      competitive for Na+. These results indicate that the inhibitor acts inside the
      cell, unlike ouabain, and thus its action mechanism appears to be original.

PMID- 9657346
TI  - Metabolic studies in a patient with severe carnitine palmitoyltransferase type II
      deficiency.
AB  - Here we report on a patient with severe ("non-classic") carnitine
      palmitoyltransferase type II (CPT II) deficiency. Hypoglycemia prompted by an
      infectious episode and associated with non-ketotic dicarboxylic aciduria
      orientated diagnosis towards beta-oxidation deficiency disorders. Blood carnitine
      levels revealed a secondary carnitine deficiency that was responsive to oral L
      carnitine supplementation. Blood acylcarnitine profiles were abnormal and
      included acetyl (C2:0), butyryl/isobutyryl (C4:0), isovaleryl/2-methylbutyryl
      (C5:0), hexanoyl (C6:0), myristoyl (C14:0), palmitoyl (C16:0), hexadecenoyl
      (C16:1), oleyl (C18:1) and stearoyl (C18:0) carnitine. In urine, excess excretion
      of dicarboxylylcarnitines, mainly dodecanedioylcarnitine, was noticed. Upon
      carnitine supplementation, C8 to C12 fatty acylcarnitines, with decanoylcarnitine
      as well as C10 to C14 dicarboxylylcarnitines being prominent, were observed in
      urine. Biochemical measurements disclosed a severe reduction of mitochondrial CPT
      II activity (7% of normal values). Correlations of metabolic findings in the
      patient and physiological roles of CPT II are briefly discussed.

PMID- 9657347
TI  - Improved fluorometric enzymatic sorbitol assay in human blood.
AB  - Samples for use in the fluorometric enzymatic assay of sorbitol in erythrocytes
      are normally prepared using HClO4 and K2CO3. We have replaced these reagents with
      NaOH and ZnSO4. Human whole blood, erythrocyte and plasma samples prepared with
      NaOH and ZnSO4 are colorless and clear, while erythrocyte samples prepared with
      HClO4 and K2CO3 are a pale yellow-brown color. The sorbitol dehydrogenase
      reaction in the supernatant of the mixture of NaOH and ZnSO4 is inhibited, but
      ethylenediaminetetraacetate completely eliminates this effect. The sorbitol assay
      in erythrocytes prepared with NaOH and ZnSO4 shows higher sensitivity and
      reproducibility than did that with HClO4 and K2CO3. Recovery of sorbitol added to
      erythrocytes is similar in both assay methods. Concentrations of whole blood and
      erythrocyte sorbitol assayed by the present method are significantly higher in
      diabetics than in normals. Poorly controlled diabetics had higher whole blood and
      erythrocyte sorbitol than well-controlled diabetics. Whole blood sorbitol
      concentrations differed more between diabetic and normal subjects than did
      erythrocyte sorbitol concentrations.

PMID- 9657348
TI  - Human pancreatic reg protein immunoenzymatic assay and molecular form in serum.
AB  - A direct sandwich immunoassay was developed to quantify the human reg protein, a
      non enzymatic pancreatic acinar protein the biological function of which remains
      elusive. Polystyrene balls were coated with specific IgG fraction as the first
      antibody and horseradish peroxidase labelled IgG was used as a second antibody.
      The linearity of the assay was good over a concentration range of 1.25-100 ng/ml
      and the good parallelism obtained between the standard and the assay dilution
      curves in serum and pancreatic juice indicates the absence of non-specific
      interfering reactions. Gel filtration of serum showed that the reg protein was
      eluted in the fractions corresponding to the proteins of around 25 kDa and that
      the chromatographic behaviour of the serum protein was identical to that of the
      purified pancreatic protein when added to serum. This assay was simple, specific,
      sensitive and reproducible and may permit the determination of low levels of reg
      protein in different biological fluids.

PMID- 9657349
TI  - Blood glutamate levels in patients with motor neuron disease.
AB  - This study was undertaken to evaluate the role of excitatory amino acid glutamate
      (Glu) in the pathophysiology of motor neuron disease (MND). It was observed that
      blood Glu levels were significantly higher in MND patients with respect to
      healthy controls. The data indicate that Glu homeostasis is altered in the
      patients with MND.

PMID- 9657350
TI  - Lipid profile in various phases of menstrual cycle and its relationship with
      percentage plasma volume changes.

PMID- 9657351
TI  - Sialic acid content of von Willebrand factor subunit. A simple method for
      quantitative estimation.

PMID- 9657352
TI  - Sensory CGRP depletion by capsaicin exacerbates hypoxia-induced pulmonary
      hypertension in rats.
AB  - Pulmonary hypertension is a debilitating disease that occurs among infants and
      adults. One of many etiologies is airway hypoxia. We previously demonstrated a
      role of endogenous calcitonin gene-related peptide (CGRP), a potent vasodilator,
      in ameliorating the pulmonary vascular pressor response to chronic hypoxia and
      related changes in the lungs and heart. This study evaluates the role of
      endogenous sensory CGRP in hypoxic pulmonary hypertension and examines the
      intrinsic neural microcircuitry. Rats were pretreated with capsaicin i.p. to
      deplete pulmonary sensory C-fiber stores of CGRP and substance P and placed in
      hypobaric hypoxia (10% O2, 16 days) or normoxia together with sham controls.
      Hypoxia increased pulmonary artery pressure, right-ventricular weight, arterial
      medial thickness, elasticized capillaries, endothelial cell density, lung water
      and hematocrit in control rats. Capsaicin augmented pulmonary artery pressure and
      right-ventricular hypertrophy in hypoxia, and medial thickness and endothelial
      cell density both in normoxia and hypoxia. Because of the limited effects on
      these parameters by substance P and other capsaicin-sensitive lung agents, our
      results suggest that sensory CGRP deficit severely exacerbates pathological signs
      of hypoxic pulmonary hypertension. A neural microcircuitry consistent with an
      axon reflex pathway is outlined histochemically. We conclude that endogenous CGRP
      modulates pulmonary vascular tone in hypoxic pulmonary hypertension which
      requires intact primary sensory fibers.

PMID- 9657353
TI  - Effect of continuous infusion of vasopressin on glomerular growth response in
      spontaneously hypertensive rats.
AB  - Vasopressin (VP) is thought to play an important role in the pressor and
      proliferative responses of renal glomeruli. We have utilized the spontaneously
      hypertensive rat (SHR) model to determine if glomerular proliferation is induced
      by chronic infusion of exogenous VP. SHR were continuously infused with 0.1
      ng/kg/min VP (H-VP group), 1.0 ng/kg/min (H-VP group), or vehicle alone (control
      group) for fifteen days using osmotic minipumps, and the histological alterations
      and level of expression of platelet-derived growth factor B-chain (PDGF-B) and
      transforming growth factor (TGF)-beta1 mRNA were determined. We observed no
      significant differences in systolic blood pressure, heart rate, serum
      electrolytes, protein and creatinine among the three groups of rats, but urine
      volume was found to be significantly decreased, and urine osmolality
      significantly increased, in the H-VP group. Kidney weight was significantly
      higher in the H-VP and L-VP groups than in the control group, and glomerular
      diameter was higher in the H-VP group. When we measured mesangial injury score
      and cellularity in the glomeruli of these animals, we observed VP dose-dependent
      proliferative changes. In the immunofluorescence study, although we did not find
      an obvious difference in depositions of collagen types III, IV and VI, alpha
      smooth muscle actin and PDGF-B among the groups, the collagen type I and TGF
      beta1 increased in several glomeruli in the H-VP group. Reverse transcription
      polymerase chain reaction (RT-PCR) revealed no significant differences in the
      glomerular levels of PDGF-B mRNA among the three groups of rats, but the level of
      expression of TGF-beta1 mRNA was significantly higher in the L-VP and H-VP groups
      than in the control group. These findings suggest that VP may contribute to
      glomerular proliferation, and that VP may exert its effects in part through the
      induction of TGF-beta1 expression. These results also raise the possibility that
      blockade of VP receptors may be useful in the treatment of some forms of
      glomerular disease.

PMID- 9657354
TI  - Sympathetic pathways mediate GLP-1 actions in the gastrointestinal tract of the
      rat.
AB  - The aim of this study was to establish the actions of GLP-1 (7-37) on
      gastrointestinal motility in rats. We prepared anaesthetized Sprague-Dawley rats
      with strain-gauges in the antrum, duodenum and the proximal jejunum and a
      catheter in the aorta close to the coeliac artery for close infusion of
      substances. Intraarterial GLP-1 infusions (3 x 10(-10) and 3 x 10(-9) moles/kg
      per 10 min) (n = 8) induced inhibition of spontaneous motor activity in the
      antrum, duodenum and proximal jejunum. Inhibition induced by GLP-1 was reversed
      by i.v. infusion of GLP-1 receptor antagonist, Exendin (9-39) (3 x 10(-8)
      moles/kg per 10 min) (n = 6). Neither the presence of L-NNA (10(-5) moles/kg) (n
      = 9) nor the VIP receptor antagonist [4-Cl-D-Phe6, Leu17]-VIP (3 x 10(-8)
      moles/kg per 10 min) (n = 8) modified responses to GLP-1. However, a combination
      of the adrenergic blockers phentolamine and propranolol (1 mg/kg each) (n = 8)
      completely blocked motor actions of GLP-1 in all the organs studied. Moreover,
      inhibition of gastrointestinal motor activity by GLP-1 was blocked by previous
      infusion of hexamethonium (10 mg/kg) (n = 4). This study demonstrates that GLP-1
      inhibits gastrointestinal motor activity of the rat acting on specific GLP-1
      receptors and via stimulation of adrenergic pathways.

PMID- 9657355
TI  - Stimulation of ACTH and GH release by angiotensin II in normal men is mediated by
      the AT1 receptor subtype.
AB  - This study was performed in order to determine whether the stimulatory effect of
      plasma angiotensin II (ANG II) on Adrenocorticotropic hormone (ACTH) and growth
      hormone (GH) secretion in humans is mediated by AT1 subtype receptors. For this
      purpose, the effects of the administration of the AT1 receptor antagonist,
      losartan (50 mg p.o.) or a placebo on the ACTH and GH responses to ANG II (i.v.
      infusion for 60 min of successively increasing doses (4, 8 and 16 ng/kg/min);
      each dose for 20 min) were evaluated in eight normal men. ANG II infusion induced
      significant increases in both serum ACTH and GH levels (mean peaks were 1.6- and
      four-times higher than baseline, respectively). The ACTH response to ANG II was
      completely abolished by pretreatment with losartan. Also, the ANG II-induced GH
      rise was reduced by administration of losartan, but the GH response was still
      significantly higher than the basal value (mean peak was twice as high as the
      baseline). These data provide evidence of AT1 receptor involvement in mediation
      of the ANG-II stimulating effect on ACTH and GH secretion.

PMID- 9657356
TI  - Diazepam binding inhibitor and total cholesterol plasma levels in cirrhosis and
      hepatocellular carcinoma.
AB  - Cholesterol is used by cells for biosynthetic processes and for steroid
      synthesis. Although the role of cholesterol in tumorigenesis is not clear it is
      known that steroids are important factors in human carcinogenesis. A polypeptide,
      diazepam binding inhibitor (DBI), which is an endogenous ligand for peripheral
      benzodiazepine receptors enhances steroidigenesis by promoting cholesterol
      delivery to the inner mitochondrial membrane which represents the rate-limiting
      step of steroid biosynthesis. We have assayed the total cholesterol (TC) and the
      DBI plasma concentrations in patients with liver cirrhosis complicated by
      hepatocellular carcinoma (HCC) in comparison with those of uncomplicated liver
      cirrhosis. TC and DBI levels have been studied in 73 cirrhotic patients and in 23
      patients with HCC. Both TC and DBI levels were higher in HCC patients when
      compared with age, sex and Child-Pugh class matched cirrhotic controls. The
      values (mean+/-S.D.) in patients in Child-Pugh class B and C with and without HCC
      were respectively 128+/-30 mg/dl vs. 106+/-27 mg/dl (P < 0.01) and 2.05+/-0.78
      pmol/ml vs. 0.78+/-0.84 pmol/ml (P < 0.0001). The data may be the result of the
      metabolic influence of tumors that enhances steroid biosynthesis during tumor
      proliferation.

PMID- 9657357
TI  - Effects of long term treatment with corticotropin releasing factor on
      corticotropic tumor cells in vitro.
AB  - hCRF inhibits proliferation of corticotropic tumor cells cultivated in serum
      reduced medium via interaction with CRF-receptors. This effect was attenuated by
      the specific antagonist hCRF (9-41), but not by a variety of substances which are
      inhibitors of cAMP production or cAMP-dependent kinases, suggesting that the
      effect was not mediated via cAMP. The growth inhibiting effect of hCRH was
      developed after 4 h incubation, a longer hCRF treatment did not change the effect
      observed after 4 h. Simultaneously, after hCRF treatment for 4 days the cells
      were insensitive for ACTH release by hCRF stimulation despite of an increase in
      the number of secretory granules. The results show that the inhibition of
      proliferation of pituitary tumor cells by hCRF seems to be a rapid receptor
      mediated process connected with morphological changes, but not mediated via
      activation of adenylate cyclase.

PMID- 9657358
TI  - Effect of bombesin at low doses on the secretion of the exocrine pancreas and on
      plasma gastrin concentration in the conscious pig.
AB  - We investigated the role of low-doses of bombesin in the regulation of exocrine
      secretion in the pancreas of the conscious pig. In ten growing castrated male
      Large White pigs, bombesin was infused intravenously for 1 h at doses of 0 to 500
      pmol/kg/h under a stimulation of secretin (36 pmol/kg/h). In six pigs, bombesin
      (50 pmol/kg/h) was administered alone for 2 h and its effect on pancreatic
      secretion was compared to that of an infusion of secretin. The pancreatic juice
      and the blood were collected at 15-min intervals for use in assays of protein in
      the juice and gastrin in the plasma. When bombesin was infused alone or in
      combination with secretin, the volume secreted was not altered. The protein
      output was not altered by secretin, but was increased by the infusion of
      bombesin, in a dose-dependent manner, reaching a plateau at 250 pmol/kg/h. The
      plasma gastrin levels were increased by bombesin, starting with the 50 pmol/kg/h
      dose. This effect was maximal at a dose of 100 pmol/kg/h. The levels remained
      below those measured after a standard meal, demonstrating that the effect of
      bombesin on the studied parameters is of physiological significance.

PMID- 9657359
TI  - Receptor mechanisms of bradykinin-mediated activation of prenodal lymphatic
      smooth muscle.
AB  - We have previously shown that several endogenous vasoactive agents constrict
      prenodal lymph vessels in the canine forelimb. In this study, we assessed the
      receptor mechanisms by which bradykinin activates lymphatic smooth muscle.
      Intralymphatic (i.l.) infusion of bradykinin at concentrations of 3.82 x 10(-6),
      3.82 x 10(-5) and 3.82 x 10(-4) molar significantly increased lymphatic perfusion
      pressure. To determine the potential role of lymphatic alpha-receptors in this
      response, we infused bradykinin at a concentration of 3.82 x 10(-4) molar i.l.
      before and during intra-arterial (i.a.) phentolamine administration. Prior to
      phentolamine, bradykinin resulted in a doubling of the lymphatic perfusion
      pressure. Phentolamine alone had no effect on the resting lymphatic pressure, but
      significantly reduced forelimb arterial pressures. When the infusion of
      bradykinin was repeated during phentolamine administration, there was no
      significant change in the lymphatic perfusion pressure. To determine the subclass
      of alpha-adrenergic receptors involved in this response, we infused bradykinin
      and the alpha1-receptor agonist phenylephrine i.l. before and during
      administration of i.a. prazosin, a specific alpha1-receptor antagonist, i.a.
      Prior to prazosin, both phenylephrine and bradykinin significantly increased
      lymphatic perfusion pressure. During prazosin administration, neither
      phenylephrine nor bradykinin significantly altered the lymphatic perfusion
      pressure. These data indicate that bradykinin-mediated increases in prenodal
      lymphatic smooth muscle tone are mediated by lymphatic alpha1-adrenergic
      receptors.

PMID- 9657360
TI  - Inhibition of gastric acid secretion by galanin in rats. Relation to endogenous
      histamine release.
AB  - Inhibitory effect of galanin on basal and secretagogs-stimulated gastric acid
      secretion was investigated in urethane-anesthetized rats. A rat stomach was
      mounted in an ex-vivo chamber, perfused with saline, and either gastric acid or
      alkaline secretion was determined by titrating the perfusate. Gastric mucosal
      blood flow (GMBF) was measured by a laser Doppler flowmeter. Intravenous infusion
      of galanin dose-dependently inhibited the increase of acid secretion induced by
      pentagastrin and carbachol but not by histamine, without any influence on the
      GMBF response. Galanin also reduced basal acid secretion while increasing GMBF,
      but did not evoke any change in basal gastric alkaline secretion. M15, which is a
      galanin receptor antagonist in the central nervous system but acts as a full
      agonist in the gastrointestinal smooth muscle, also suppressed pentagastrin
      induced acid secretion, similar to galanin. In addition, pentagastrin increased
      the release of histamine into the gastric lumen, and this response was
      significantly inhibited by galanin. These results suggest that the inhibitory
      effect of galanin on acid secretion is mediated by suppression of endogenous
      histamine release from enterochromaffin-like cells and that the process may be
      related to the activation of the same subtype of galanin receptors as in the
      central nervous system and pancreatic beta-cells.

PMID- 9657361
TI  - An aminoisobutyric acid-containing analogue of the cockroach tachykinin-related
      peptide, LemTRP-1, with potent bioactivity and resistance to an insect
      angiotensin-converting enzyme.
AB  - Nine tachykinin-related peptides (TRPs), designated LemTRP-1-9, were recently
      isolated from the cockroach, Leucopheae maderae. To obtain a LemTRP resistant to
      endo- and exoprotease-mediated hydrolysis, we synthesized a peptide with one of
      the carboxy terminus residues substituted for a sterically hindered
      aminoisobutyric acid (Aib) and with the amino terminus blocked with a
      pyroglutamate. The Aib-containing analogue of the nonapeptide LemTRP-1 (Aib
      LemTRP-1) thus has the sequence pGlu-Ala-Pro-Ser-Gly-Phe-Leu-Aib-Val-Arg-NH2.
      This analogue was shown to be resistant to hydrolysis by recombinant angiotensin
      converting enzyme (ACE), from Drosophila melanogaster. Endogenous LemTRP-1 on the
      other hand was rapidly hydrolysed by ACE at the Gly7-Val8 bond, resulting in a
      single heptapeptide. The Aib-LemTRP-1 has about the same potency as LemTRP-I in
      inducing contractions of the L. maderae hindgut muscle. It was also tested in
      intracellular recordings for ability to induce firing of action potentials in
      dorsal unpaired median (DUM) neurons in the metathoracic ganglion of the locust
      Locusta migratoria. The Aib-containing analogue was nearly as active as LemTRP-1
      and the natural ligand locustatachykinin I. LemTRP-1 and Aib-LemTRP-1 had the
      same transient time course of action on the cockroach hindgut. This suggests that
      peptide degradation is not likely to be the cause of the transient action of
      TRPs.

PMID- 9657362
TI  - Fat metabolism during exercise: a review. Part I: fatty acid mobilization and
      muscle metabolism.
AB  - This is the first part in a series of three articles about fat metabolism during
      exercise. In this part the mobilization of fatty acids and their metabolism will
      be discussed as well as the possible limiting steps of fat oxidation. It is known
      for a long time that fatty acids are an important fuel for contracting muscle.
      After lipolysis, fatty acids from adipose tissue have to be transported through
      the blood to the muscle. Fatty acids derived from circulating TG may also be used
      as a fuel but are believed to be less important during exercise. In the muscle
      the IMTG stores may also provide fatty acids for oxidation after stimulation of
      hormone sensitive lipase. In the muscle cell, fatty acids will be transported by
      carrier proteins (FABP), and after activation, fatty acyl CoA have to cross the
      mitochondrial membrane through the carnitine palmytoyl transferase system, after
      which the acyl CoA will be degraded to acetyl CoA for oxidation. The two steps
      that are most likely to limit fat oxidation are fatty acid mobilization from
      adipose tissue and transport of fatty acids into the mitochondria along with
      mitochondrial density and the muscles capacity to oxidize fatty acids.

PMID- 9657363
TI  - Detraining effects on bone mass in young male rats.
AB  - The effects of exercise training and detraining on bone mass were assessed in
      young male Wistar rats. The rats were divided randomly into sedentary control (C)
      and exercise training (T) groups. The T rats were trained for 10 weeks followed
      by a 10-week detraining period. Training consisted of running exercise on a
      rodent treadmill at 35 m/min, +5-degree inclination, 60 min/day, 5 days/week.
      Training induced significant gain in fat-free dry weight and length of bones
      (femur, tibia, humerus and coxa) and bone mineral content (femur, tibia and
      humerus). Histological analysis at the tibial mid-shaft revealed a significant
      increase in total and cortical areas without a significant change in marrow area
      in the T group. Bone mass acquired through running exercise was retained for 10
      weeks after cessation of training. These results indicate that running exercise
      leads to increased cortical bone associated with enhanced periosteal bone
      formation which is also maintained even after stopping exercise training, and
      suggest that training effects on the skeleton in bone mass level do not diminish
      immediately after cessation of training.

PMID- 9657364
TI  - Endurance training and its effect upon the activity of the GH-IGFs system in the
      elderly.
AB  - There is an age-associated decline in the activity of the GH-IGFs system.
      However, so far, it has not been studied, whether this decline in somatotrophic
      activity might be preventable by intensive exercising. We studied 11 elderly male
      (50-78 years) marathon runners and 10 age-matched male (52-73 years) sedentary
      controls to evaluate plasma concentrations of GH, total and free IGF-I and IGF-II
      and of IGF-binding protein-1 (IGFBP-1), IGFBP-2, IGFBP-3 and insulin. When
      comparing the two groups (runners vs controls) no differences were found in GH
      (1.0 +/- 1.2 vs 1.3 +/- 1.3 microg/l [mean +/- SD]), IGF-1 (115 +/- 23 vs 113 +/-
      21 microg/l), IGF-II (961 +/- 192 vs 864 +/- 125 microg/l), free IGF-1 (227 +/-
      80 vs 318 +/- 146 ng/l), free IGF-II (563 +/- 249 vs 492 +/- 108 ng/l), IGFBP-3
      (2403 +/- 515 vs 2307 +/- 326 microg/l) or insulin (26 +/- 13 vs 27 +/- 18 mU/l).
      However, IGFBP-1 (4.44 +/- 2.61 vs 2.28 +/- 0.93 microg/l) and IGFBP-2 (493 +/-
      143 vs 340 +/- 186 microg/l) were found to be significantly increased in marathon
      runners. In conclusion, our findings do not support the hypothesis that the age
      associated decline in GH, IGF-1 and IGFBP-3 may be preventable by intensive
      endurance training. However, marathon running affects the regulation of the GH
      IGFs system activity at the level of IGFBP-1 and -BP-2.

PMID- 9657365
TI  - Visual and brainstem auditory evoked potentials and maximal aerobic exercise:
      does the influence of exercise persist after body temperature recovery?
AB  - Transversal studies have shown a strong correlation between specific evoked
      potential (EP) values and specific physical activities, as well as between EP
      values and the amount of training. Prior to longitudinal studies investigating
      the effect of training in EPs, it is mandatory to determine whether a recent
      training session could interfere with regular EP recording. Exercise-induced
      hyperthermia is known to modify EP values. The purpose of the study was to
      determine whether an acute exercise can induce EP modification persisting after
      body temperature recovery. We measured two sets of visual evoked potentials
      (VEPs) and brainstem auditory evoked potentials (BAEPs) in 16 males (8 cyclists
      and 8 sedentary peers), one before and the other after a maximal cycloergometric
      graded exercise test. The second test was performed immediately after body
      temperature recovery. We chose to test cyclists, as their specific training
      corresponded to the exercise test we performed on a cycloergometer. The repeated
      measures before and after the exercise test showed no significant differences,
      neither in VEPs nor in BAEPs, for any subject of the study. Recording VEPs and
      BAEPs in cyclists, we observed no difference related to this particular sport
      training. This study showed that VEP and BAEP values were similar to those
      measured before a maximal exercise when body temperature returned to pre-exercise
      value. This original work demonstrated that VEP and BAEP recordings can be
      reliably performed after a recent training session, provided body temperature has
      returned to basal level.

PMID- 9657366
TI  - Endurance training in females: changes in beta-endorphin and ACTH.
AB  - Previous results from endurance training in women have been discrepant in regard
      to influences on basal and maximum adrenocorticotropin (ACTH) and beta-endorphin
      (beta-EP) concentrations before and after exhaustive exercise. A group of 23
      untrained young women ran 3 times a week for 30 min at an individual specific
      intensity corresponding to their respective anaerobic threshold, derived from the
      lactate performance curve obtained from prior treadmill testing. ACTH and beta-EP
      were measured at rest, as well as 5 and 30 min after exhaustive progressive
      spiroergometric treadmill running, both before and after the 8 week endurance
      training program. Basal beta-EP did not change after training, but less elevated
      concentrations were measured both 5 (p < 0.05) and 30 min (p < 0.05) after
      exercise, after the training program. In contrast, the resting concentration of
      ACTH increased significantly; the respective maximum concentration was less
      elevated after 5 min and much less elevated 30 min after the exercise (p < 0.05).
      Positive correlations were found after the exhaustive exercise between beta-EP
      and ACTH, as well as between maximum lactate and ACTH. Training was associated
      with significant changes in maximum running speed (p < 0.01), maximum oxygen
      uptake (p < 0.01) and the running speed at the anaerobic threshold (p < 0.05).
      Maximum lactate and the level of perceived exertion remained unchanged, showing a
      similar level of exhaustion. Our results indicate that endurance training
      modulates the hormonal responses of beta-EP and ACTH to comparable workloads of
      high intensity. After the training program the maximum concentrations are
      significantly lower during the recovery period. The tendency to elevated basal
      ACTH, and thus elevated cortisol, might be a new factor to consider in evaluation
      of endurance training induced hormonal disturbances in women.

PMID- 9657367
TI  - Comparison of muscle cross-sectional areas between weight lifters and wrestlers.
AB  - The purpose of this study was to investigate the difference in the magnitude of
      muscular development between Olympic weight lifters and wrestlers through the
      measurements of fat-free mass (FFM) and limb muscle cross-sectional area (CSA).
      Subjects were college Olympic weight lifters (N = 34, age = 20.0 +/- 1.3 years,
      stature = 1.67 +/- 0.07 m, body mass = 70.1 +/- 10.2 kg, X +/- SD) and wrestlers
      (N = 33,20.3 +/- 1.2 years, 1.69 +/- 0.06 m, 71.0 +/- 1.8 kg) who had identical
      range of body mass. Body density and the CSAs of reciprocal muscle groups in the
      forearm, upper arm, lower leg and thigh were measured by underwater weighing and
      B-mode ultrasound methods, respectively. No significant difference was found in
      body density between the weight lifters (1.077 +/- 0.007 g x ml(-3)) and
      wrestlers (1.076 +/- 0.008 g x ml(-3)). Moreover, FFM and the CSA values of all
      muscle groups tested were similar in the two groups of weight-classified
      athletes, with an exception that the wrist flexor CSA was significantly larger in
      wrestlers than in weight lifters, and the knee extensor and thigh (extensors +
      flexors) CSAs were larger in weight lifters than in wrestlers. The total muscle
      CSA of every site was significantly correlated to FFM2/3 in the separate groups;
      r = 0.714 to 0.815 (p < 0.05) in weight lifters and r = 0.769 to 0.919 (p < 0.05)
      in wrestlers. While the CSA-to-FFM2/3 ratios of the upper arm and wrist flexor
      muscles were significantly higher in wrestlers than in weight lifters, those of
      the thigh and knee extensor muscles were higher in weight lifters than in
      wrestlers. Thus, the present results suggest that an event-related difference
      exists in the magnitude of limb muscle CSA between competitive weight lifters and
      wrestlers of similar FFM.

PMID- 9657368
TI  - Effect of recovery duration on the force-velocity relationship.
AB  - The aim of this study was to investigate the effect of different Recovery
      Duration (RD) between each sprint (30 s, 1 min, 3 min, 5 min, 10 min and 24 h)
      during the force-velocity test and to analyse associated anaerobic parameters
      such as maximal anaerobic power and blood lactate concentrations. Twelve male
      physical education students aged from 18 to 26 years took part in this study.
      Maximal anaerobic power (Pmax) was not statistically different whatever the
      recovery duration (from 885 to 938 watts, for RD 30 s to RD 24 h, respectively).
      This was associated with a tendency during the longer RD tests for optimal
      velocity to decrease (p = ns) while optimal force increased (p < 0.05). Blood
      lactate concentrations were regularly increased from 1.7 to a 9 mmol x l(-1)
      plateau at sprint 4 for RD tests < 10 min and were quite stable from the second
      sprint with an associated value from 2.2 to 4.7 mmol x l(-1) for RD 10 min and RD
      24 h. In spite of statistically different values for [L]s between the tests, the
      power developed for each sprint remained unchanged. These data indicate that the
      attainment of maximal power seems independent from the recovery duration (> 10 s)
      and the pre-blood lactate values observed between each sprint during the force
      velocity test. The way to reach Pmax was different between the tests. Different
      partition of energetic pathways are suggested. In conclusion, the force-velocity
      test could be performed with a shorter and the arbitrary five minutes recovery
      duration.

PMID- 9657369
TI  - Aerobic and anaerobic energy expenditure during exhaustive ramp exercise.
AB  - Ramp tests are often manipulated so that oxygen uptake is able to interpret
      energy expenditure in its entirety. We hypothesized that oxygen deficits during
      ramp exercise to exhaustion would be significant, providing a more complete
      description of the types of energy expenditure available for this mode of
      testing. Oxygen deficits were obtained during a slow ramp (681 +/- 71 s) and a
      fast ramp (275 +/- 33 s) to exhaustion. Twelve healthy men (age 35 +/- 3 yrs;
      VO2max 51 +/- 10 ml x kg(-1) x min(-1)) performed several 10 min submaximal bike
      rides (at or below ventilatory threshold) to determine work rate -O2 uptake
      demands. Estimated O2 demands were compared to measured O2 uptake during each
      ramp test, the difference representing an oxygen deficit. Work levels were
      controlled and measurements collected with a commercially available electrically
      braked bike ergometer and metabolic testing system (MedGraphics, Minn., MN). Data
      were collected and averaged in 30 s time periods, power in watts (W), energy
      expenditure in cumulative O2 (L). Using a paired t-test, cumulative O2 uptakes
      were significantly lower (p = 0.0001) when measured O2 uptakes (26.0 L +/- 4.5
      for slow ramp; 10.8 L +/- 2.8 for fast ramp) were compared to estimated O2
      demands (29.0 L +/- 3.7 for slow ramp; 14.1 L +/- 3.5 for fast ramp). Anaerobic
      energy expenditures (oxygen deficits) represented 10.8% and 23.4% of total energy
      expenditure for slow ramps and fast ramps, respectively. Comparisons of the
      slopes for each test condition revealed significant differences (steady state >
      slow ramp > fast ramp; p = 0.0001,ANOVA). We conclude that the oxygen deficit
      during ramp testing represents a significant part of total energy expenditure.

PMID- 9657370
TI  - Erythropoietin (rHuEPO) doping: effects of exercise on anaerobic metabolism in
      rats.
AB  - The purpose of this study was to investigate the effects of recombinant human
      erythropoietin (rHuEPO) administration on energy metabolism during exercise.
      Specifically, the contribution of anaerobic (glycogen) metabolism during exercise
      was evaluated. Sprague-Dawley rats were randomly assigned to an experimental
      [rHuEPO] (600 U x kg(-1) of Eprex, every 3 days) or control (equivalent volume of
      saline) group. After 15 days of treatment, animals from both groups were randomly
      subjected to either a 30-minute exercise (swimming with 5% body weight added) or
      resting period. They were sacrificed at the end of the exercise period. Their
      liver and muscles were quickly removed and frozen in liquid nitrogen. Blood was
      also sampled. rHuEPO administration resulted in a significant (P < 0.05) increase
      of hematocrit (from 42 +/- 2 to 54 +/- 7 L/L). In the rHuEPO group, both muscle
      glycogen and free fatty acids were higher whereas lactate was lower at the
      conclusion of the exercise period (P < 0.05). These results suggest that energy
      substrate utilization during exercise is affected by enhanced oxygen
      availability. Finally, a lower overall contribution to energy production from
      anaerobic metabolism during exercise followed rHuEPO administration.

PMID- 9657371
TI  - Detection of human chorionic gonadotrophin misuse in sports.
AB  - The peptide hormone human chorionic gonadotrophin (hCG) was measured in the urine
      of 5663 male athletes collected for doping analysis in Flanders during the period
      1993-1996. Using the Abbott IMx hCG procedure, the free and whole molecule
      associated beta-subunit of human chorionic gonadotrophin was determined.
      Statistical evaluation of the data results in a far outside value of 2.28 mIU/ml.
      The decision limit, i.e. the concentration at which a sportsman will be
      considered positive, is set at 5 mIU/ml to ensure with the greatest possible
      degree of certainty that no false positive results are reported.

PMID- 9657372
TI  - Mode of receptor binding and activation by plasminogen-related growth factors.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) and macrophage stimulating
      protein (MSP) are plasminogen-related kringle proteins that lost serine protease
      domain enzymatic activity and became ligands for cell surface tyrosine kinase
      receptors. They are activated by cleavage to disulfide-linked alphabeta chains.
      Surprisingly, despite structural similarities, the high affinity receptor binding
      regions of the two proteins are different: alpha chain for HGF, and beta chain
      for MSP. We propose that after cleavage exposes a beta chain binding site (high
      affinity for MSP, low affinity for HGF), monomeric ligand induces receptor
      dimerization and activation via alpha and beta chain binding sites of different
      affinity.

PMID- 9657373
TI  - Secondary structure of some elements of 18S rRNA suggests that strongylid and a
      part of rhabditid nematodes are monophyletic.
AB  - Analysis of the secondary structure of 18S rRNA molecules in nematodes revealed
      some new traits in the secondary structure peculiar to their hairpin 17. Some of
      them are characteristic of all the nematodes, whereas others are characteristic
      exclusively of the order Rhabditida. The loss of a nucleotide pair in the highly
      conservative region of hairpin 17 distinguishes 18S rRNA of the Strongylida and
      some species of the Rhabditida from other nematodes and, moreover, from all other
      organisms. Hence, it is possible to regard the Strongylida and a part of the
      Rhabditida including Caenorhabditis elegans as a new monophyletic taxon.

PMID- 9657374
TI  - An NMR-based identification of peptide fragments mimicking the interactions of
      the cathepsin B propeptide.
AB  - Selected fragments of the 62-residue proregion (or residues 1p-62p) of the
      cysteine protease cathepsin B were synthesized and their interactions with
      cathepsin B studied by use of proton NMR spectroscopy. Peptide fragments 16p-51p
      and 26p-51p exhibited differential perturbations of their proton resonances in
      the presence of cathepsin B. These resonance perturbations were lost for the
      further truncated 36p-51p fragment, but remained in the 26p-43p and 28p-43p
      peptide fragments. Residues 23p-26p or TWQ25A in the N-terminal 1p-29p fragment
      did not show cathepsin B-induced resonance perturbations although the same
      residues had strongly perturbed proton resonances within the 16p-51p peptide.
      Both the 1p-29p and 36p-51p fragments lack a common set of hydrophobic residues
      30p-35p or F30YNVDI35 from the proregion. The presence of residues F30YNVDI35
      appears to confer a conformational preference in peptide fragments 16p-51p, 26p
      51p, 28p-43p and 26p-43p, but the same residues induce the aggregation of
      peptides 16p-36p and 1p-36p. The peptide fragment 26p-43p binds to the active
      site, as indicated by its inhibition of the catalytic activity of cathepsin B.
      The cathepsin B prosegment can therefore be reduced into smaller, but functional
      subunits 28p-43p or 26p-43p that retain specific binding interactions with
      cathepsin B. These results also suggest that residues F30YNVDI35 may constitute
      an essential element for the selective inhibition of cathepsin B by the full
      length cathepsin B proregion.

PMID- 9657375
TI  - Overexpression of hMTH1 mRNA: a molecular marker of oxidative stress in lung
      cancer cells.
AB  - Human MutT homologue (hMTH1) mRNA was overexpressed in SV-40-transformed non
      tumorigenic human bronchial epithelial cells (BEAS-2B cells) and in 11 out of 12
      human lung cancer cell lines relative to normal human bronchial epithelial cells.
      Expression levels of hMTH1 mRNA were inversely proportional to cellular levels of
      8-oxo-deoxyguanosine. Together, these results suggest that hMTH1 gene expression
      may represent a molecular marker of oxidative stress that could ultimately be
      used to elucidate the temporal relationships between oxidative stress, genomic
      instability and the development of lung cancer.

PMID- 9657376
TI  - Structural and dynamic helix geometry alterations induced by mismatch base pairs
      in double-helical RNA.
AB  - A ribooligonucleotide microhelix derived from the acceptor stem of Escherichia
      coli tRNA(Ala) having a C3-A70 mismatch in place of the G3-U70 wobble pair in the
      wild-type tRNA(Ala), and a sequence variant with a regular U3-A70 base pair have
      been investigated by NMR. In vivo, suppressor tRNA(Ala) variants with C3-A70 (as
      well as several other) mismatch pairs are substrates for alanyl-tRNA synthetase
      (ARS), supporting the hypothesis of an 'indirect' recognition of the identity
      element 3-70 mismatch pair via structural modifications caused by the mispair in
      comparison to canonical A-RNA helices. It is demonstrated that the C-A mismatch
      likewise induces helix geometry alterations, in particular with respect to base
      stacking in the vicinity of the mismatch. However, with reference to the 'wild
      type' G3-U70 microhelix, destacking in the C3-A70 acceptor stem duplex occurs in
      the opposite direction from the mismatch pair. Therefore it is concluded that the
      locally enhanced conformational flexibility or dynamics associated with the
      structural changes induced by the mismatch pairs could be an essential
      prerequisite for optimal adaptation of the tRNA(Ala) acceptor stem to the contact
      region of the ARS.

PMID- 9657377
TI  - The carboxy-terminal domain of the receptor-associated protein binds to the
      Vps10p domain of sortilin.
AB  - Binding of the receptor-associated protein (RAP) to the newly identified putative
      sorting receptor, sortilin, was analyzed by surface plasmon resonance analysis of
      recombinant RAP and sortilin domains and compared with binding to megalin and low
      density lipoprotein receptor-related protein (LRP). The data show that the RAP
      binding site in sortilin is localized in the cysteine-rich lumenal part
      homologous to yeast vacuolar protein-sorting 10 protein (Vps10p), and the
      sortilin-binding site in RAP is localized in the carboxy-terminal domain III of
      the three homologous domains in RAP. Whereas sortilin bound only RAP domain III,
      megalin and LRP bound all RAP domains with the functional affinity order: domain
      III >domain I > domain II.

PMID- 9657378
TI  - Total chemical synthesis of bovine pancreatic trypsin inhibitor by native
      chemical ligation.
AB  - Bovine pancreatic trypsin inhibitor (BPTI) is an important model for the study of
      protein folding. Herein we describe a robust approach to the total chemical
      synthesis of BPTI using native chemical ligation of unprotected peptide segments
      in aqueous solution. After refolding and oxidative formation of disulfides, the
      target protein was purified by affinity chromatography. The synthetic BPTI was
      characterized by mass spectrometry, inhibition assay, thermal denaturation and 2D
      NMR spectroscopy, and was shown to be structurally and functionally identical to
      natural BPTI. The synthetic strategy presented in this paper has enabled us to
      establish rapid access to novel analogues of BPTI.

PMID- 9657379
TI  - Identification of a structural requirement for thyroid Na+/I- symporter (NIS)
      function from analysis of a mutation that causes human congenital hypothyroidism.
AB  - Patients with congenital lack of I transport do not accumulate I in their
      thyroids, often resulting in severe hypothyroidism. A single amino acid
      substitution in the thyroid Na+/I- symporter (NIS), proline replacing threonine
      at position 354 (T354P), was recently identified as the cause of this condition
      in two independent patients. Here we report that the lack of I- transport
      activity in T354P NIS generated by site-directed mutagenesis, is not due to a
      structural change induced by proline, but rather to the absence of a hydroxyl
      group at the beta-carbon of the amino acid residue at position 354. Hence, this
      hydroxyl group is essential for NIS function.

PMID- 9657380
TI  - A new opioid peptide predicted from cloned cDNAs from skin of Pachymedusa
      dacnicolor and Agalychnis annae.
AB  - We have isolated a cDNA encoding a precursor of dermorphin from the skin of
      Pachymedusa dacnicolor. Besides four copies of this opioid peptide, the deduced
      sequence also contains the genetic information for a novel peptide Tyr-Ile-Phe
      His-Leu-Met-Asp-NH2. This differs from Met-deltorphin by the presence of Ile at
      position 2. In a related precursor from the skin of Agalychnis annae, the
      sequence of this peptide is in the 3'-untranslated region of the cloned cDNA.
      From earlier results we predict that in skin peptides the second residue is D
      allo-Ile. We have synthesized this and related peptides with different D-amino
      acids, and determined their delta agonist activity. The peptide with D-nor-Leu
      binds with high affinity to delta receptors, while that with D-allo-Ile is about
      100 times less active.

PMID- 9657381
TI  - A calcium pump at the higher plant nuclear envelope?
AB  - Evidence for a Ca2+-pump at the nuclear envelope (NE) in plant cells has been
      obtained using confocal and electron microscope immunocytochemistry and
      antibodies raised to a plant homologue of the mammalian SERCA pump. This is the
      first evidence suggesting an NE Ca2+-pump in plants. In addition to being
      localised with the NE in interphase, the antigen was localised to membrane
      derived from the NE and associated ER during mitosis, correlating with known Ca2+
      pools. The work suggests that a SERCA pump is present at the NE of plant as well
      as animal cells.

PMID- 9657382
TI  - On the origin of the '35-mus kinetics' of P680(+.) reduction in photosystem II
      with an intact water oxidising complex.
AB  - The origin of the '35-micros kinetics' of P680(+.) reduction in photosystem II
      (PS II) with an intact water oxidising complex has been analysed by comparative
      measurements of laser flash induced changes of the 830-nm absorption and the
      relative quantum yield of chlorophyll (Chl) fluorescence. The latter parameter
      was monitored at a time resolution of 500 ns by using newly developed home built
      equipment [Reifarth, F., Christen, G. and Renger, G. (1997) Photosynth. Res. 51,
      231-2421. It was found that: (i) the amplitudes of the unresolved ns-kinetics of
      both 830-nm absorption changes and the rise of fluorescence yield exhibit
      virtually the same period four oscillation pattern when dark adapted samples are
      excited with a train of saturating laser flashes; (ii) the corresponding
      oscillation patterns of the normalised extent of the 35-micros kinetics under
      identical excitation conditions are strikingly different with maxima after the
      3rd and 5th flash for the 830-nm absorption changes vs. pronounced maxima after
      the 4th and 8th flash for the rise of the fluorescence yield. The period four
      oscillations unambiguously show that the '35-micros kinetics' of P680(+.)
      reduction are characteristic for reactions in PS II entities with an intact water
      oxidising complex. However, the disparity of the oscillation patterns of (ii)
      indicates that in contrast to the ns components of P680(+.) reduction the 35
      micros kinetics do not reflect exclusively an electron transfer from Y(Z) to
      P680(+.). It is inferred that a more complex reaction takes place which comprises
      at least two processes: (a) P680(+.) reduction by Y(Z) and (b) coupled and/or
      competing reaction(s) which give rise to additional changes of the chlorophyll
      fluorescence yield.

PMID- 9657383
TI  - Cloning and characterization of the gene encoding the human peroxisomal assembly
      protein Pex3p.
AB  - Proteins essential for the assembly of functional peroxisomes are designated
      peroxins and are encoded by PEX genes. In yeast, Pex3p was previously identified
      as a peroxisomal integral membrane protein indispensable for peroxisome
      biogenesis and integrity. Here we report the cloning of the orthologous human
      PEX3 gene. It encodes a polypeptide of 373 amino acids (42 kDa) and is expressed
      in all tissues examined. As shown by transfection of epitope tagged constructs
      and immunofluorescence analysis, human Pex3p is localized at the peroxisome. The
      N-terminal 40 amino acids were revealed to be sufficient to target a GFP reporter
      protein to the peroxisome. A positively charged five amino acid sequence within
      this N-terminal region is highly conserved from yeast to human Pex3p.
      Overexpression of human Pex3p leads to proliferation of ER membranes in COS7
      cells. Since disruption of human peroxins has been shown to result in peroxisomal
      biogenesis disorders, PEX3 is another candidate gene being involved in this
      disease group.

PMID- 9657384
TI  - Structure and mRNA expression of a bovine trp homologue related to mammalian trp2
      transcripts.
AB  - Mammalian homologues of the transient receptor potential (trp) gene product from
      Drosophila melanogaster function as Ca2+-selective or non-selective cation
      channels. Complementary DNA was isolated from a bovine testis cDNA library which
      encodes bovine trp2 (btrp2), a protein of 432 amino acid residues comprising four
      predicted transmembrane segments. Btrp2 mRNA is expressed in bovine testis,
      spleen and liver but not in brain, heart, adrenal gland or retina. In bovine
      testis expression of btrp2 mRNA is restricted to spermatocytes but is not present
      in spermatogonia, Leydig or Sertoli cells suggesting that btrp2 may contribute to
      the formation of ion channels in sperm cells.

PMID- 9657385
TI  - Oxidative stress and hypoxia/reoxygenation trigger CD95 (APO-1/Fas) ligand
      expression in microglial cells.
AB  - Apoptosis plays an important role in neurodegeneration, although the mechanisms
      and mediators in the brain are largely unknown. Because microglial cells have
      been suggested to contribute to apoptosis in neurological disorders, we
      investigated the expression of the death ligand CD95L in this cell type. We found
      that, compared to classical mediators of microglial activation, the most potent
      inducer of CD95L was oxidative stress. Exposure of microglial cells to H2O2 or
      paraquat rapidly triggered CD95L mRNA and protein expression, associated with the
      activation of transcription factor NF-kappaB. Enhanced expression of CD95L was
      further found following exposure of cells to hypoxia and subsequent
      reoxygenation. Our results indicate a potential role of CD95L in oxidative stress
      mediated cell death, ischemia/reperfusion and other diseases with a disturbed
      redox balance.

PMID- 9657386
TI  - Substrate-dependent activation requirements and kinetic properties of protein
      kinase C.
AB  - Protein kinase C (PKC) requires basic amino acids around the phosphorylated Ser
      or Thr. Previous studies of the effector requirements of PKCs alpha, beta and
      gamma with two commonly used substrates, MBP3-14 (AQKRPSQRSKYL) and peptide
      epsilon (ERMRPRKRQGSVRRRV), revealed that MBP3-14 phosphorylation required Ca2+,
      phosphatidylserine and diacylglycerol, while peptide epsilon supported high
      levels of phosphatidylserine-dependent activity in the absence of Ca2+ or
      diacylglycerol. Since the Arg versus Lys content is much larger in peptide
      epsilon than in MBP3-14, we examined the role of these amino acids in conferring
      substrate-dependent effector requirements for PKC activation. We substituted Lys
      for Arg in peptide epsilon (peptide epsilon[R-->K]) and Arg for Lys in MBP3-14
      (MBP3-14[K-->R]) and analyzed the effector requirements and kinetic properties of
      PKCs alpha, beta and gamma with the parent and modified peptides. In general,
      significant Ca2+ and diacylglycerol dependence was observed with peptide
      epsilon[R-->K] as compared to peptide epsilon. On the other hand, the effector
      requirements with MBP3-14[K-->R] were the same as with MBP3-14, presumably due to
      a subthreshold Arg content. Both Km and Vmax determined in the presence of Ca2+,
      phosphatidylserine and diacylglycerol were increased by the peptide epsilon
      modification for all three isoenzymes, while the only effect of MBP3-14
      modification was a decrease in Km for PKCbeta. Km and Vmax values for peptide
      epsilon and peptide epsilon[R-->K] phosphorylation by PKCalpha were also
      determined in the absence of Ca2+ or diacylglycerol. While diacylglycerol had no
      effect, Ca2+ decreased the Km for both substrates to a similar extent. Overall,
      the degree of effector dependence did not correlate with absolute Km values. The
      mechanism of PKC activation by Arg-rich substrates, therefore, does not involve
      their ability to bind to the active site.

PMID- 9657387
TI  - Structural stabilization of botulinum neurotoxins by tyrosine phosphorylation.
AB  - Tyrosine phosphorylation of botulinum neurotoxins augments their proteolytic
      activity and thermal stability, suggesting a substantial modification of the
      global protein conformation. We used Fourier-transform infrared (FTIR)
      spectroscopy to study changes of secondary structure and thermostability of
      tyrosine phosphorylated botulinum neurotoxins A (BoNT A) and E (BoNT E). Changes
      in the conformationally-sensitive amide I band upon phosphorylation indicated an
      increase of the alpha-helical content with a concomitant decrease of less ordered
      structures such as turns and random coils, and without changes in beta-sheet
      content. These changes in secondary structure were accompanied by an increase in
      the residual amide II absorbance band remaining upon H-D exchange, consistent
      with a tighter packing of the phosphorylated proteins. FTIR and differential
      scanning calorimetry (DSC) analyses of the denaturation process show that
      phosphorylated neurotoxins denature at temperatures higher than those required by
      non-phosphorylated species. These findings indicate that tyrosine phosphorylation
      induced a transition to higher order and that the more compact structure
      presumably imparts to the phosphorylated neurotoxins the higher catalytic
      activity and thermostability.

PMID- 9657388
TI  - The mating factor response pathway regulates transcription of TEC1, a gene
      involved in pseudohyphal differentiation of Saccharomyces cerevisiae.
AB  - The transcription factor Tec1 is involved in pseudohyphal differentiation and
      agar-invasive growth of Saccharomyces cerevisiae cells. The sole element in the
      TEC1 promoter that has thus far been shown to control Tec1 function is the
      filament response element. We find that the TEC1 promoter also contains several
      pheromone response element sequences which are likely to be functional: TEC1
      transcription is induced by mating factor, cell cycle regulated and dependent on
      the Ste4, Ste18 and Ste5 components of the mating factor signal transduction
      pathway. Using alleles of the transcription factor Ste12 that are defective in
      DNA binding, transcriptional induction or cooperativity with other transcription
      factors, we find little correlation between TEC1 transcript levels and agar
      invasive growth.

PMID- 9657389
TI  - Adhesion-related glycocalyx study: quantitative approach with imaging-spectrum in
      the energy filtering transmission electron microscope (EFTEM).
AB  - Large polysaccharide molecules composing the glycocalyx have been shown to
      prevent cell adhesion. However, this process was not observed microscopically.
      Terbium labeling, combined with a new quantitative imaging method based on
      electron energy loss spectroscopy, allowed specific glycocalyx staining with
      excellent contrast. Image analysis enabled us to compare glycocalyx structure in
      free membrane areas and contacts between monocytic cells and bound erythrocytes.
      Apparent glycocalyx thickness, in contact areas, was half of the sum of
      glycocalyx thicknesses in free areas without label density increase.
      Ultrastructural immunogold localization of CD43 molecules, a major component of
      glycocalyx, was also demonstrated to be excluded from contact areas during
      adhesion. Thus, both approaches strongly suggest that some glycocalyx elements
      must exit from contact to allow binding of adhesion molecules.

PMID- 9657390
TI  - Binding of a native titin fragment to actin is regulated by PIP2.
AB  - Titin is a giant protein which extends from Z-line to M-line in striated muscles.
      We report here the purification of a 150-kDa titin fragment, obtained after V8
      protease treatment of myofibrils. This polypeptide was located at the N1-line
      level, in a titin part known to exhibit stiff properties correlated to an
      association with actin. By solid or liquid phase binding assays and
      cosedimentation, we have clearly demonstrated a direct, saturable and relative
      high affinity binding of the native titin fragment to F-actin. The 150-kDa titin
      fragment was also shown to accelerate actin polymerization. Furthermore, the
      actin-titin interaction was found to be inhibited by phosphoinositides.

PMID- 9657391
TI  - Intrahelical side chain interactions in alpha-helices: poor correlation between
      energetics and frequency.
AB  - Polypeptide sequences in proteins may increase their tendency to adopt helical
      conformations in several ways. One is the recruiting of amino acid residues with
      high helical propensity. Another is the appropriate distribution of residues
      along the helix to establish stabilising side chain interactions. The first
      strategy is known to be followed by natural proteins because amino acids with
      high helical propensity are more frequent in alpha-helices. If proteins also
      followed the second strategy, stabilising amino acid pairs should be more
      frequent than others. To test this possibility we compared empirical energies of
      side chain interactions in alpha-helices with statistical energies calculated
      from a data base of proteins with low homology. We find some correlation between
      the stability afforded by the pairs and their relative abundance in alpha-helices
      but the realisation of energetic preferences into statistical preferences is very
      low. This indicates that natural alpha-helices do not regularly use intrahelical
      side chain interactions to increase their stability.

PMID- 9657392
TI  - Recombinant expression, purification and characterization of Kch, a putative
      Escherichia coli potassium channel protein.
AB  - The Escherichia coli gene kch, similar in primary structure to eukaryotic voltage
      gated potassium channels, was cloned and overexpressed in E. coli. The protein
      was solubilized from the plasma membrane with dodecylmaltopyranoside,
      lauryldimethylamine oxide or N-laurylsarcosine and was purified in milligram
      amounts by imidazole elution from a nickel-chelate column. The molecular mass of
      the purified protein in a number of detergents with 12 carbon atom chains
      suggests that rKch forms primarily tetramers of the 50 kDa monomers. CD
      spectroscopy of the purified protein indicates a significant alpha-helical
      content that is preserved upon addition of SDS.

PMID- 9657393
TI  - The cloning and developmental regulation of murine diacylglycerol kinase zeta.
AB  - Diacylglycerol kinases (DGKs) regulate the key signaling intermediates
      diacylglycerol (DAG) and phosphatidic acid (PA). We isolated cDNA clones of mouse
      diacylglycerol kinase zeta (mDGKzeta) and found that it shares 88% identity at
      the nucleic acid level and 95.5% identity at the amino acid level with human
      DGKzeta (hDGKzeta). Murine DGKzeta protein rose gradually during embryonic
      development, and was abundant in newborn and adult brains. By RNA whole-mount in
      situ hybridization, mDGKzeta was shown to be expressed in spinal ganglia and limb
      buds at low level in E11.5 embryos and at higher level in E12.5 embryos. In E13.5
      embryos, DGKzeta mRNA was highly expressed in vibrissa follicles, in spinal
      ganglia, and in the interdigital regions of the developing limbs. Northern
      blotting showed that DGKzeta expression was limited to specific anatomical
      regions of the brain. Thus, the expression of DGKzeta is regulated temporally and
      spatially during mammalian development and correlates with the development of
      sensory neurons and regions undergoing apoptosis.

PMID- 9657394
TI  - The chloroplast Ndh complex mediates the dark reduction of the plastoquinone pool
      in response to heat stress in tobacco leaves.
AB  - We have examined the effects of heat stress on electron transfer in the thylakoid
      membrane of an engineered plastid ndh deletion mutant, delta1, incapable of
      performing the Ndh-mediated reduction of the plastoquinone pool in the
      chloroplast. Upon heat stress in the dark, the rate of PSII-independent reduction
      of PSI after subsequent illumination by far-red light is dramatically enhanced in
      both delta1 and a wild-type control plant (WT). In contrast, in the dark, only
      the WT shows an increase in the reduction state of the plastoquinone pool. We
      conclude that the heat stress-induced reduction of the intersystem electron
      transport chain can be mediated by Ndh-independent pathways in the light but that
      in the dark the dominant pathway for reduction of the plastoquinone pool is
      catalysed by the Ndh complex. Our results therefore demonstrate a functional role
      for the Ndh complex in the dark.

PMID- 9657395
TI  - Restoration of phytanic acid oxidation in Refsum disease fibroblasts from
      patients with mutations in the phytanoyl-CoA hydroxylase gene.
AB  - Refsum disease (RD) is biochemically characterized by the excessive accumulation
      of phytanic acid in tissues and body fluids due to deficiency of phytanoyl-CoA
      hydroxylase (PAHX). In this study, we screened three RD patients and identified a
      novel deletion (88 amino acids), and a missense mutation (Arg275Trp) in the
      previously reported PAHX cDNA (Jansen et al., 1997; Mihalik et al., 1997).
      Moreover, transfection of skin fibroblasts from two RD patients with wild-type
      PAHX gene restored the activity for alpha-oxidation of phytanic acid. Southern
      analysis on a somatic cell hybrid panel detected the PAHX gene on chromosome 10,
      corroborating radiation hybrid and homozygosity mapping data (Mihalik et al.,
      1997; Nadal et al., 1995).

PMID- 9657396
TI  - Role of two conserved glycine residues in the beta-propeller domain of the
      integrin alpha4 subunit in VLA-4 conformation and function.
AB  - The N-terminal region of the alpha integrin subunits is predicted to fold into a
      beta-propeller domain. Using K562 alpha4 transfectants we show that mutations at
      alpha4 subunit residues Gly130 and Gly190 affect the conformation of this domain
      causing a reduction in the recognition of alpha4 by anti-alpha4 antibodies which
      map to the beta-propeller. The improper alpha4 conformation also led to an
      altered association with the beta1 subunit, and to a lack of alpha4beta1 adhesion
      to VCAM-1 and CS-1/fibronectin, as well as an abolishment of anti-alpha4- and
      anti-beta1-dependent homotypic aggregation. The total conservation of Gly130 and
      Gly190 among integrin alpha subunits suggests their importance in the correct
      folding of their respective beta-propeller domains, and thus, in the adhesive
      activity of the integrins.

PMID- 9657397
TI  - Accreditation of echocardiography laboratories.

PMID- 9657398
TI  - Safety of dobutamine stress echocardiography supervised by registered nurse
      sonographers.
AB  - Dobutamine stress echocardiography (DSE) is widely used for the diagnosis and
      evaluation of coronary artery disease. Studies examining the safety of this
      technique typically have involved DSE supervised by physicians. At the Mayo
      Clinic, experienced registered nurse (RN) sonographers were trained to perform
      DSE under the direct supervision of a physician. To prove that the safety of DSE
      was not compromised with the change in supervision, we examined data from 1035
      consecutive outpatient studies: 516 patients were monitored by cardiologists or
      cardiology fellows (group 1) and 519 were monitored by trained RN sonographers
      (group 2). Risk factors, history of coronary artery disease, stress parameters,
      and complication rates were similar in both groups. In group 1, one patient
      experienced sustained ventricular tachycardia requiring treatment. In group 2,
      one patient experienced ventricular fibrillation during recovery and was
      successfully resuscitated. Outpatient DSE is safe when supervised by RN
      sonographers.

PMID- 9657399
TI  - Prognostic implications of a normal dobutamine-atropine stress echocardiogram in
      patients with chest pain.
AB  - To assess the prognostic significance of a normal dobutamine-atropine stress
      echocardiogram in relation to the pretest probability of coronary artery disease
      (CAD), 200 consecutive patients (86 men and 114 women, mean [SD] age 59 [13]
      years) with a stable chest pain syndrome and a normal dobutamine-atropine stress
      echocardiogram were followed-up for 21 +/- 16 months. Outcome events were cardiac
      death, non-fatal myocardial infarction, and coronary revascularization
      procedures. Low (<10%), intermediate (10% to 80%), and high (>80%) pretest
      probabilities of CAD were present in 27 (14%), 108 (54%), and 65 (33%) patients,
      respectively. During follow-up, 2 patients (annual event rate 0.6%) had cardiac
      death, none had nonfatal myocardial infarction, and 4 patients (annual event rate
      1.1%) underwent a coronary revascularization procedure. All patients with cardiac
      events had high pretest probabilities of CAD. Patients with cardiac death (but
      unproven significant CAD) had maximal tests without angina or ischemic
      electrocardiographic changes. In contrast, all patients with subsequent coronary
      revascularization had dobutamine-induced angina or ischemic electrocardiographic
      changes, and all except one study were submaximal. We conclude that patients with
      a stable chest pain syndrome and normal findings on dobutamine-atropine stress
      echocardiograms have an excellent cardiac prognosis. However, patients with
      typical angina, high pre-test probabilities of CAD, and stress-induced angina or
      ischemic electrocardiographic changes, and in particular those with submaximal
      stress, still appear to be at risk for functionally important CAD despite a
      normal dobutamine-atropine stress echocardiogram.

PMID- 9657400
TI  - Assessment of coronary flow reserve by transesophageal echocardiography in
      cardiac transplant recipients.
AB  - This study investigated the feasibility of dipyridamole Doppler transesophageal
      echocardiography to assess coronary flow reserve in 26 patients with orthotopic
      heart transplantation and compared it with positron emission tomography. We found
      an 85% success rate in obtaining Doppler flow signals in the proximal left
      anterior descending coronary artery. Our data also showed that the correlation
      between transesophageal echocardiography and dipyridamole N-13 ammonia positron
      emission tomography increases when respective resting rate-pressure products are
      taken into account. However, comparison between the two methods should be made
      with caution because coronary flow reserve derived from transesophageal
      echocardiography tends to be higher than that obtained with positron emission
      tomography.

PMID- 9657401
TI  - Left ventricular ejection fraction in patients with normal and distorted left
      ventricular shape by three-dimensional echocardiographic methods: a comparison
      with radionuclide angiography.
AB  - BACKGROUND: Serial evaluation of left ventricular (LV) ejection fraction (EF) is
      important for the management and follow-up of cardiac patients. Our aim was to
      compare LVEF calculated from two three-dimensional echocardiographic (3DE)
      methods with multigated radionuclide angiography (RNA), in patients with normal
      and abnormally shaped ventricles. METHODS AND RESULTS: Forty-one consecutive
      patients referred for RNA underwent precordial rotational 3DE acquisition of 90
      cut-planes. From the volumetric data set, LVEF was calculated by (a) Simpson's
      rule (3DS) through manual endocardial tracing of LV short-axis series at 3 mm
      slice distance and (b) apical biplane modified Simpson's method ( MS) in 29
      patients by manual endocardial tracing of the apical four-chamber view and its
      computer-derived orthogonal view. Patients included three groups: A, 17 patients
      with LV segmental wall motion abnormalities; B, 13 patients with LV global
      hypokinesis; and C, 11 patients with normal LV wall motion. For all the 41
      patients, there was excellent correlation, close limits of agreement, and
      nonsignificant difference between 3DS and RNA for LVEF calculation (r = 0.99, [
      6.7, +6.9] and p = 0.9), respectively. For the 29 patients, excellent correlation
      and nonsignificant differences between LVEF calculated by both 3DS and BMS and
      values obtained by RNA were found (r = 0.99 and 0.97, p = 0.7 and p = 0.5,
      respectively). In addition, no significant difference existed between values of
      LVEF obtained from RNA, 3DS, and BMS by the analysis of variance (p = 0.6). The
      limits of agreement tended to be closer between 3DS and RNA (-6.8, +7.2) than
      between BMS and RNA (-8.3, +9.7). The intraobserver and inter-observer
      variability of RNA, 3DS, and BMS for calculating LVEF(%) were (0.8, 1.5), (1.3,
      1.8), and (1.6, 2.6), respectively. There were closer limits of agreement between
      3DS and RNA for LVEF calculation in A, B, and C patient subgroups [(-3.5, +5), (
      8.4, +5.6), and (-7.8, +8.6)] than that between BMS and RNA [(-8.1, +10.7), (
      11.9, +9.3), and (-9.1, +11.3)], respectively. CONCLUSIONS: No significant
      difference existed between RNA, 3DS, and BMS for LVEF calculation. 3DS has better
      correlation and closer limits of agreement than BMS with RNA for LVEF
      calculation, particularly in patients with segmental wall motion abnormalities
      and global hypokinesis. 3DS has a comparable observer variability with RNA.
      Therefore the use of 3DS for serial accurate LVEF calculation in cardiac patients
      is recommended.

PMID- 9657402
TI  - Rates of left ventricular isovolumic pressure rise and fall from the aortic
      regurgitation velocity signal: description of the method and validation in human
      beings.
AB  - BACKGROUND: Aortic regurgitation results from a pressure gradient across the
      aortic valve during left ventricular (LV) isovolumic relaxation, LV filling, and
      isovolumic contraction periods. Assuming the applicability of the simplified
      Bernoulli equation to this pressure-flow relation and constancy of aortic
      pressure during LV isovolumic relaxation and contraction periods, one can
      theoretically obtain estimates of the rates of LV isovolumic pressure fall and
      rise (deltaP/delta t) from the aortic regurgitation (AR) velocity signal. METHODS
      AND RESULTS: Mitral regurgitation (MR) and AR signals were recorded by using the
      continuous wave Doppler technique in 26 patients with combined mitral and aortic
      regurgitant lesions. The LV negative deltaP/delta t was obtained by dividing the
      time taken for the AR velocity to rise from 1 m/sec to 2.5 m/sec into 21 mm Hg,
      which is the estimated LV pressure drop between these points. In a similar
      fashion, the LV positive deltaP/delta t was obtained between 2.5 m/sec and 1
      m/sec of the fast decelerating portion of the AR signal. The LV negative
      deltaP/delta t by the AR method ranged from 420 to 3500 mm Hg/sec and correlated
      well with that obtained by the MR method obtained in a blinded fashion (r = 0.95,
      p < 0.0001). The mean (SD) difference between the two methods was 30 (129) mm
      Hg/sec. Similarly, the LV positive deltaP/delta t by the AR method (range 420 to
      2625 mm Hg/sec) correlated closely with that obtained by the MR method (r = 0.93,
      p < 0.0001), with the mean (SD) difference between the two methods being 38 (138)
      mm Hg/sec. CONCLUSIONS: Preliminary data presented in this study indicate the
      feasibility of obtaining a reliable estimate of LV positive and negative
      deltaP/delta t from the AR velocity profile. Thus the examination of the AR
      signal may give valuable insights into both LV systolic and diastolic functions.

PMID- 9657403
TI  - Role of intraoperative transesophageal echocardiography in determining aortic
      annulus diameter in homograft insertion.
AB  - The sizing of aortic valve (AV) homografts for optimum function requires an
      accurate measurement of the aortic annulus. Typically, this measurement is
      obtained directly with sizers in the open aorta. We describe the use of
      intraoperative transesophageal echocardiography (IOTEE) to measure the aortic
      annulus and select the appropriate AV homograft before cardiopulmonary bypass and
      aortic cross-clamping. Thirty-two patients underwent AV homograft insertion
      between March 1993 and March 1996 and had IOTEE. There were 13 women and 19 men.
      Mean age was 58 +/- 14 years. IOTEE measurements were satisfactory in sizing in
      all patients, and no extraordinary surgical measures were necessary to insert the
      AV homografts. Early postoperative follow-up showed trivial or mild regurgitation
      of all homografts. Prebypass IOTEE is reliable in guiding the selection of
      optimal AV homografts.

PMID- 9657404
TI  - Quantification of mitral regurgitation by the automated cardiac output method: an
      in vitro and in vivo study.
AB  - BACKGROUND: Recently, the automated cardiac output method (ACM) was introduced
      for the calculation of blood flow at the left ventricular outflow tract (LVOT).
      This study was performed to examine the possibility of using ACM for flow
      calculation at the level of the mitral valve and for the quantification of mitral
      regurgitation (MR) in vitro and in vivo. METHODS AND RESULTS: In a computer
      controlled in vitro model of the human heart, aortic and mitral normal
      bioprosthetic valves were inserted. ACM and electromagnetic probe flow
      measurements correlated well at the LVOT and at the mitral level (r2 = 0.79 and
      0.77, respectively). For stroke volumes ranging from 30 to 100 ml/beat, there was
      no statistically significant bias between ACM and electromagnetic flow probe (
      1.5 and 1.3 ml for LVOT and mitral level, respectively). Limits of agreement were
      [-14; +11] ml and [-18; +16] ml, respectively. We evaluated 68 patients in our in
      vivo study. They were divided into three groups according to the results of
      "standard" echocardiographic Doppler methods for the semiquantification of MR:
      echocardiographic color Doppler cartography, intensity of the continuous wave
      Doppler spectra, and in some patients, pulmonary venous flow, conventional
      Doppler, and proximal isovelocity surface area quantitative data. Group 1
      consisted of 35 patients without MR or a physiologic one; the 17 patients in
      group 2 had a mild MR (1-2/4) and in group 3, 16 patients with MR 3-4/4 were
      included. Regurgitant volume (RV) was calculated as the difference between ACM
      mitral flow and ACM aortic flow, and regurgitant fraction (RF) was defined as the
      ratio between RV and ACM mitral flow. When mitral flow was measured only from the
      four-chamber view, we found in group 1, RV = -0.57 (0.67) L/min and RF = -16%
      (19%); in group 2, RV = -0.31 (1.06) L/min and RF = -8% (19%); and in group 3, RV
      = 1.53 (0.94) L/min and RF = 23% (13%). RV and RF were statistically higher in
      group 3 compared with group 2 or group 1 (p < 0.0005), but no significant
      difference was found between groups 1 and 2. When mitral flow was measured by the
      mean value of ACM four-chamber and two-chamber views, this resulted in group 1,
      RV = -0.26 (0.63) L/min and RF = -8% (15%); in group 2, RV = 0.01 (1.04) L/min
      and RF = -2% (18%); and in group 3, RV = 2.07 (1.21) L/min and RF = 34% (19%). RV
      and RF were again significantly higher in group 3 (p < 0.0001). There was no
      significant difference between group 1 and group 2, but in group 1 RF was no
      longer statistically different from 0%. CONCLUSIONS: (1) In our in vitro setting,
      ACM is reliable both at the LVOT and at the mitral valve. (2) In the in vivo
      situation, some overlapping does exist between the three groups of MR. However,
      ACM is a very easy, rapid, and objective method to differentiate hemodynamic
      nonsignificant (<3/4) from significant (> or =3/4) MR. Together with other well
      known methods for the quantification of MR, it should facilitate the gradation of
      MR in the clinical setting. The absence of significant differences between group
      1 and group 2 proves that the accuracy of ACM measurements at the mitral valve
      needs to be ameliorated before ACM can be used as a gold standard for the
      noninvasive measurement of RV and RF.

PMID- 9657405
TI  - Evaluation of tricuspid regurgitation severity: echocardiographic and clinical
      correlation.
AB  - The correlation between 19 echocardiographic markers of tricuspid regurgitation
      (TR) severity and findings on physical examination was studied in 66 consecutive
      patients (age 63 +/- 12 years) with moderate or severe TR. Clinical TR was
      defined by two or more of the following: prominent jugular venous pulse V waves,
      pulsating liver, and sea-saw parasternal movement. Thirty-eight patients (57.6%)
      had clinical TR, whereas 28 patients (42.4%) did not. In a univariate analysis,
      the most powerful predictors of clinical TR (p < 0.01) were jet area > or =9 cm2,
      right atrial area > or =30 cm2, jet width at origin > or =0.8 cm, systolic flow
      reversal in the hepatic veins, paradoxical septal movement, diastolic septal
      flattening, inferior vena cava diameter > or =2.1 cm, and lack of inferior vena
      cava respiratory variation. Regurgitant index was a weaker predictor.
      Multivariate analysis showed that the only independent echocardiographic
      predictor of clinical TR was systolic flow reversal (positive and negative
      predictive values 91.2% and 78.1%, respectively). Significant echocardiographic
      TR can be subclinical in a substantial number of patients.

PMID- 9657406
TI  - Visualization of clear echocardiographic images with near field noise reduction
      technique: experimental study and clinical experience.
AB  - BACKGROUND: With transthoracic echocardiography, it is sometimes difficult to
      obtain a clear image of the apical portion of the heart because of noise near the
      transducer. To reduce this artifact, we have developed a new technique (near
      field noise reduction, NFNR) based on the digital filtering by using
      radiofrequency signals. This technique may be useful for the accurate measurement
      of the wall thickness of the myocardium in the near field. The objectives of
      these studies were (1) to determine the accuracy of this new technique for the
      measurement of wall thickness in the experimental study and (2) to determine
      whether the improvement in the image quality in the apical portion can be
      obtained in the clinical setting by using the NFNR technique. EXPERIMENTAL STUDY:
      By using the NFNR technique, we measured wall thickness of three kinds of
      phantoms (wall thickness 9.0, 14.0, and 21.0 mm) moving at various velocities (5
      to 80 mm/sec) in the water bath with artifact produced by a single probe. It was
      difficult to obtain clear echocardiographic images of the phantom and measure its
      wall thickness because of the artifact. By using the NFNR technique, on the other
      hand, the same phantom was clearly imaged. It was possible to measure the wall
      thickness of each phantom at each moving velocity with the NFNR technique. Mean
      differences between the echocardiographic measurement and actual value of wall
      thickness in each phantom model (9.0, 14.0, and 21.0 mm) were 0.04 +/- 0.58 mm,
      0.09 +/- 0.58 mm, and -0.02 +/- 0.24 mm, respectively. CLINICAL STUDY: We studied
      25 initial patients in whom the near field was not clearly imaged in apical views
      by conventional echocardiography because of near field noise. Apical four-chamber
      or two-chamber views were obtained with and without the NFNR technique. Two
      observers independently graded endocardial visualization for the 50 segments by
      using a three-point scale (0 = endocardium not seen, 1 = seen in part but not all
      of the segment, 2 = endocardium seen along entire segment). The mean segment
      score in the imaging with the NFNR technique was significantly higher than that
      without the NFNR technique (observer 1: 1.8 +/- 0.7 vs 1.2 +/- 0.8, p < 0.01;
      observer 2: 1.6 +/- 0.7 vs 1.2 +/- 0.8, p < 0.01). CONCLUSIONS: The newly
      developed NFNR technique provides clear echocardiographic images and accurate
      wall thickness measurement in the experimental model even when it is difficult to
      obtain clear images because of the artifact. This new technique will be useful in
      the reduction of near field noise in the clinical setting.

PMID- 9657407
TI  - Multiplane transesophageal echocardiography in diagnosis of anomalous origin of
      the left coronary artery from the pulmonary artery: a case report.
AB  - Anomalous origin of the left coronary artery from the pulmonary artery in adults
      is difficult to identify reliably by transthoracic echocardiography (TTE). We
      describe a 32-year-old woman with this coronary anomaly mimicking a coronary
      artery fistula on conventional TTE study. This anomaly was suggested by
      multiplane transesophageal echocardiography (TEE) and subsequently confirmed by
      coronary angiography. Multiplane TEE thus may serve as a first-line diagnostic
      tool for detecting anomalous origin of coronary arteries.

PMID- 9657408
TI  - Anterior mitral valve aneurysm: evaluation by three-dimensional echocardiography.
AB  - Three-dimensional reconstruction of cardiac structures is becoming increasingly
      important. Complete spatial visualization of cardiac structures and their
      relation to each other enable better understanding of both morphologic and
      functional lesions.

PMID- 9657409
TI  - Myxoma of the left atrial appendage mimicking thrombus during aortic valve
      replacement.
AB  - Echocardiographic characterization of cardiac masses involving the left atrium
      are defined by morphologic shape and appearance, site of attachment, type of
      margins, and presence or absence in the left atrial appendage. Most reports use
      location in the LAA as strong supportive evidence of thrombus, especially if
      associated with other suggestive findings (i.e., atrial fibrillation, spontaneous
      echo contrast, or both). Other reported masses (non-thrombi) in the left atrial
      appendage are considered extremely rare. We report a case of a patient with
      coexisting aortic stenosis and atrial fibrillation diagnosed intraoperatively by
      transesophageal echocardiography with myxoma of the left atrial appendage.

PMID- 9657410
TI  - A case of hepatic hernia with echocardiographic findings simulating right atrial
      tumor.
AB  - A patient with hepatic hernia was found to have echocardiographic findings
      resembling a right atrial tumor. Magnetic resonance imaging was useful in
      establishing a definitive diagnosis of hepatic hernia. Hepatic hernias should be
      ruled out when a right atrial tumor is suspected on the basis of transthoracic
      echocardiographic findings.

PMID- 9657411
TI  - Antisocial behavior: its relation to selected sociodemographic variables and
      alcohol and drug use among Mexican students.
AB  - This study is part of the National School Survey on drug use by high school
      students in Mexico. The validity, reliability, and results of the Antisocial Acts
      Scale in Mexico City (n = 3,501) are discussed. Using factorial analyses of the
      Antisocial Acts Scale, two major sources of variability were observed. The first
      one is related to antisocial acts with severe social consequences, in which
      violence and drug selling are included, and the second one is related to thefts.
      Significant differences were found in the number of offenses among groups of
      different gender, age, and occupation during the previous year. More antisocial
      acts were perpetrated by alcohol and drug users than by nonusers. In a logistic
      regression model, it was found that the main risk factors for perpetrating
      antisocial acts were being male, using alcohol, and using other drugs.

PMID- 9657412
TI  - Children in the streets of Brazil: drug use, crime, violence, and HIV risks.
AB  - The presence of vast numbers of unsupervised and unprotected children is a
      phenomenon that is common throughout Latin America, and in few places are the
      street children more visible, and reviled, than in Brazil. Estimates of their
      numbers in Brazil have ranged from 7 to 17 million, but more informed assessments
      suggest that between 7 and 8 million children, ages 5 to 18, live and/or work on
      the streets of urban Brazil. Accounts of drug misuse among street youths in
      Brazil are commonplace. Numerous scientific studies and media stories have
      reported the widespread use of inhalants, marijuana and cocaine, and Valium among
      street children. Also common is the use of coca paste and Rohypnol. Risk of
      exposure to HIV is rapidly becoming an area of concern because of the large
      number of street youths engaging in unprotected sexual acts, both renumerated and
      nonrenumerated. Moreover, Brazil's street children are targets of fear. Because
      of their drug use, predatory crimes, and general unacceptability on urban
      thoroughfares, they are frequently the targets of local vigilante groups, drug
      gangs, and police "death squads." Although there have been many proposals and
      programs for addressing the problems of Brazilian street youth, it would appear
      that only minimal headway has been achieved.

PMID- 9657413
TI  - Psychosocial, substance use, and delinquency differences among Anglo, Hispanic
      White, and African-American male youths entering a juvenile assessment center.
AB  - Using data collected on nearly 4,000 Anglo, Hispanic White, and African-American
      male youths processed at the Hillsborough County Juvenile Assessment Center, we
      examine their psychosocial, substance use, and other delinquent behavior
      differences. In extending the results of previous research in a manner consistent
      with the concept of relative deviance, significant differences in these variables
      are found across the three groups. Implications of the findings for theory,
      service delivery, and policy are also considered.

PMID- 9657414
TI  - Nurturing for careers in drug use and crime: conduct norms for children and
      juveniles in crack-using households.
AB  - A very sizable proportion of juvenile delinquents and adult criminals come from
      backgrounds and family kin systems having deviant parents or kin. This paper
      provides a focus upon the child-rearing practices directly observed by trained
      ethnographer during a case study of one highly criminal, drug-using household/kin
      network. The concrete expectations (and actual practices--called conduct norms-
      with which the household adults respond to (or "nurture") children and juveniles
      are delineated. While children are taught to "pay attention" to what adults do,
      adults typically model various deviant activities and rarely engage in
      conventional behaviors. Drug-using, and especially crack-using, men and women are
      expected not to raise (or financially support) children born to them; other kin
      expect to raise children of such unions. Children are not expected, nor able, to
      develop strong affective bonds with any household adults, and receive little or
      no psychological parenting. Adults do not take strong measures to protect
      children/juveniles from harm, and often adults are a major source of harm. In
      many ways the conduct norms in such crack-using households are well designed to
      "nurture" those persons who will be antisocial as children, delinquents as
      juveniles, and become criminals, drug misusers, and prostitutes in adulthood--and
      who have very few chances to become conventional adults.

PMID- 9657415
TI  - Using hair analysis, urinalysis, and self-reports to estimate drug use in a
      sample of detained juveniles.
AB  - This paper reports select findings of a research project designed to estimate
      drug use prevalence in a youthful offender population using hair analysis as well
      as urine testing and interviewing. The project was carried out in Cleveland,
      Ohio, and Pinellas County, Florida. The findings are consistent with earlier
      reports on prevalence estimations utilizing a bioassay component. Generally,
      respondents report drug use infrequently and test positive by assays at rates
      greater than self-reported use. Urinalysis indicates more drug prevalence than
      does interview. Hair assays, which have a greater retrospective time window, show
      even more prevalence than does urine testing. The project affirms results
      reported in 1994 by Feucht, Stephens, and Walker.

PMID- 9657416
TI  - HLA antigens in childhood onset schizophrenia.
AB  - Evidence of immune system abnormalities in adult schizophrenia has prompted
      examination of the human leukocyte antigen (HLA) system. Childhood onset
      schizophrenia offers a unique opportunity to test neurodevelopmental hypotheses
      of schizophrenia, including those which implicate components of the immune
      system. In the present study, class I and II HLA antigens were typed using
      sequence-specific primers and the polymerase chain reaction in 28 childhood onset
      schizophrenics and 51 ethnically matched healthy subjects. Groups were compared
      for frequencies of HLA antigens reported to be associated with schizophrenia
      and/or autoimmune disorders. We hypothesized that antigen frequencies would
      differ between schizophrenic and healthy children, suggesting that some dimension
      of the neurodevelopmental disturbance experienced by these children may be
      mediated by subtle abnormalities of immune function. There were no significant
      differences between schizophrenic and healthy subjects in the frequency of any
      antigen tested. These findings do not support HLA-associated pathology in
      childhood onset schizophrenia.

PMID- 9657417
TI  - Congenital dermatoglyphic malformations in severe bipolar disorder.
AB  - Dermatoglyphic alterations may be the result of early prenatal disturbances
      thought to be implicated in the aetiology of psychiatric illness. In order to
      test this hypothesis in the particular case of bipolar disorder, we assessed two
      congenital dermatoglyphic malformations (ridge dissociation (RD) and abnormal
      features (AF)) and two metric dermatoglyphic traits (total finger ridge count
      (TFRC) and total a-b ridge count (TABRC)) in a sample of 118 patients with
      chronic DSM-III-R bipolar illness, and 216 healthy controls. Bipolar cases showed
      a significant excess of RD and AF (OR = 2.80; 95% CI: 2.31-3.38) when compared
      with controls. In the cases, the presence of anomalies was associated with
      earlier age of onset. No differences were found for TFRC and TABRC. No
      associations were found with sex or familial morbid risk of psychiatric
      disorders. Our findings add further weight to the suggestion that early
      developmental disruption is a risk factor for later bipolar disorder.

PMID- 9657418
TI  - Cerebrospinal fluid prostaglandins and corticotropin releasing factor in
      schizophrenics and controls: relationship to sleep architecture.
AB  - Sleep abnormalities have been consistently observed in patients with
      schizophrenia. Elevated levels of corticotropin releasing factor (CRF) and
      prostaglandins (PGs) in the cerebrospinal fluid (CSF) of patients with
      schizophrenia have been reported, and these neurochemical substances, known to
      modulate sleep in experimental animals, may play a role in these sleep
      abnormalities. In this study, we measured PGD2, PGE2, PGF2alpha and CRF levels in
      the CSF of 14 unmedicated schizophrenic patients and 14 age- and sex-matched
      control subjects. Polysomnographic recordings were also carried out for each
      subject. As expected, the sleep of the schizophrenic subjects significantly
      differed from that of the controls; schizophrenic subjects had a longer sleep
      onset latency, slept less, spent fewer minutes in stage 2 sleep and had a lower
      sleep efficiency. We could not, however, detect any differences in CSF CRF and PG
      levels between normal and schizophrenic subjects, nor could we find any
      correlation between CSF variables and sleep parameters in the schizophrenic
      subjects and the non-psychiatric controls. These results do not favor the
      hypothesis of a role for CRF or PGs in the pathophysiology of sleep disturbances
      in schizophrenia.

PMID- 9657419
TI  - Serotonin-immune interactions in detoxified chronic alcoholic patients without
      apparent liver disease: activation of the inflammatory response system and lower
      plasma total tryptophan.
AB  - The aims of the present study were to examine (1) the inflammatory response
      system (IRS), through measurements of serum interleukin-6 (IL-6), soluble IL-6
      receptor (sIL-6R), sgp130 (the soluble form of the IL-6 transducer signal
      protein), CC16 (Clara Cell protein; an endogenous anti-cytokine), IL-1R
      antagonist (IL-1RA), IL-8 and sCD14; and (2) the availability of plasma total
      tryptophan to the brain in chronic alcoholic patients without apparent liver
      disease (AWLD). Detoxified AWLD patients had significantly lower plasma
      tryptophan and serum CC16 and significantly higher serum IL-1RA and IL-8
      concentrations than normal volunteers. There were significant correlations
      between the availability of tryptophan to the brain and serum IL-6, IL-8 and IL
      1RA (all negative) and CC16 (positive). The results suggest that (1) there is, in
      detoxified AWLD patients, an activation of the monocytic arm of cell-mediated
      immunity and a lowered anti-inflammatory capacity of the serum; and that (2)
      lower availability of plasma tryptophan to the brain in detoxified AWLD patients
      is related to activation of the IRS. Lower CC16 may be one factor predisposing
      chronic alcoholic patients toward infectious disorders.

PMID- 9657420
TI  - Platelet serotonergic functions and light therapy in seasonal affective disorder.
AB  - We investigated platelet 14C-serotonin uptake and platelet [3H]LSD and
      [3H]paroxetine binding in 11 patients with seasonal affective disorder (SAD).
      Patients were reinvestigated after light therapy, applied at 07.00-09.00 h for 10
      consecutive days. The degree of depression was rated before and after light
      therapy using the Comprehensive Psychopathological Rating Scale (CPRS). Baseline
      data in patients were compared with data from a control group consisting of 11
      age- and sex-matched healthy volunteers. Seven patients responded to light
      therapy with a > 50% reduction in CPRS scores. In non-responders, the reduction
      in CPRS was 24.7 +/- 5.5%. There was a significant inverse correlation (P =
      0.014) between Km for platelet 14C-serotonin uptake and CPRS scores. Patients had
      significantly higher Bmax for platelet [3H]LSD binding (P = 0.04) and
      significantly lower Bmax for platelet [3H]paroxetine binding (P = 0.016). There
      was a strong, multiple correlation between Bmax for [3H]LSD, as the dependent
      variable, and Km, Vmax and Bmax for [3H]paroxetine binding in patients (P <
      0.0001) but not in controls. Responders to light therapy had significantly higher
      Km (P = 0.023) and significantly lower Bmax for [3H]paroxetine binding (P =
      0.028) than non-responders. Bmax for [3H]paroxetine binding increased
      significantly to normal levels after light therapy. The results indicate that SAD
      is associated with aberrations in the serotonin uptake mechanism. The enhanced 5
      HT2-receptor density may reflect a consequential up-regulation.

PMID- 9657421
TI  - Platelet MAO activity in patients with dysthymic disorder.
AB  - The aim of the present study was to examine possible associations between
      platelet monoamine oxidase (MAO) activity and primary dysthymic disorder. For
      that purpose we estimated the enzyme activity in 58 patients (15 males and 43
      females) selected according to DSM-III-R criteria and in 61 healthy controls (30
      males and 31 females). Platelet MAO activities were found significantly lower in
      the female patients compared to female controls. Moreover, the enzyme activities
      were found to be even lower in the female patients who had attempted suicide.
      These differences did not exist in the male population. We could not find any
      associations of MAO activity to the age of the patients, the age of onset, the
      duration of dysthymia, or HAM-D and SCL-90R scores. Our findings are consistent
      with the hypothesis that platelet MAO activity is a trait-dependent indicator of
      vulnerability to dysthymic disorder and suicidality in our female population.

PMID- 9657422
TI  - Premorbid personality traits of patients with organic (ICD-10 F0), schizophrenic
      (F2), mood (F3), and neurotic (F4) disorders according to the five-factor model
      of personality.
AB  - The present article aims to examine premorbid personality traits of psychiatric
      patients with various diagnoses by asking their close relatives to
      retrospectively rate the patients' usual self with a questionnaire designed for
      the five-factor model of personality, a rapidly emerging comprehensive theory of
      personality structure. Data for 140 patients and 84 controls were analyzed.
      Although psychiatric patients as a group were characterized by high neuroticism
      and low conscientiousness when compared with the healthy controls, there were
      only a few traits that distinguished a particular diagnostic group from either
      the normal control or from the rest of the patients: neurotic disorder patients
      had higher neuroticism scores than the normal controls; unipolar depressives had
      a higher conscientiousness score than the rest of the patient group. No salient
      premorbid trait was noted for patients with organic mental disorders,
      schizophrenic disorders or bipolar disorders.

PMID- 9657423
TI  - Factors that affect social cue recognition in schizophrenia.
AB  - Earlier research (Corrigan and Green, Am. J. Psychiatry, 150 (1993) 589-594)
      showed fairly symptomatic persons with schizophrenia give more false-positive
      responses when answering questions about abstract cues in a social situation
      (i.e. affect, rules, and goals inferred about an interpersonal situation) than
      concrete cues (i.e. actions and dialogue observed in a situation). It is unclear,
      however, whether differential cue recognition is due to schizophrenia per se, or
      some aspect of the illness commensurate with significant symptoms and in-patient
      care. Moreover, the abstract and concrete dimension in the earlier study had not
      been independently validated. In this study, the 288 items of the Social Cue
      Recognition Test (SCRT) were divided into three sets based on abstraction ratings
      provided by 38 college students. The SCRT was then completed by 48 participants
      with DSM-III-R diagnoses of schizophrenia or schizoaffective disorder.
      Participants with schizophrenia were divided into low and high symptom groups
      using scores from the Brief Psychiatric Rating Scale. Results showed both low
      symptom and high symptom groups exhibited a differential deficit in cue
      recognition. False positives were greater for items rated as more abstract.
      Implications for understanding the social cognitive deficits of persons with
      schizophrenia are discussed.

PMID- 9657424
TI  - Evaluation of problem solving and communication skills of persons with
      schizophrenia.
AB  - Although much research has shown positive outcomes of teaching problem solving
      and communication skills to persons with schizophrenia, the amount of research on
      the assessment of these two sets of skills has been modest. The current study
      demonstrates an effective model for their assessment and includes a previously
      neglected procedure to determine if subjects attended to the skill prompts. It
      replicates and expands prior findings on problem solving and communication
      skills. Results indicated that persons with schizophrenia were generally deficit
      in problem solving skills. Persons without schizophrenia seemed to use more
      behavioral information when deciding if a problem existed and they were better
      able to differentiate between appropriate and inappropriate solutions to
      problems. Persons with schizophrenia were found to be deficit in communication
      skills that facilitate interaction and showed a style that subordinated their
      wants to those of others.

PMID- 9657425
TI  - Reliability of the 35% carbon dioxide panic provocation challenge.
AB  - The objective of this study was to determine the test-retest reliability of the
      35% carbon dioxide (CO2) panic provocation challenge. Thirty patients with panic
      disorder were included in this study. Twenty-four patients were challenged twice,
      with 1 week between the two challenges. Six patients dropped out after the first
      test. The 35% CO2 challenge appeared to have a good test-retest reliability; both
      on induced subjective anxiety, measured on a Visual Analogue Scale for Anxiety
      (VAS-A), and induced panic symptoms, measured with a Panic Symptom List.
      Assessing the state of anxiety immediately after the challenge gave the most
      reliable results. Calculating increase in anxiety from the pre- and post-scores
      on the VAS-A rendered less reliable scores. This study completes a series of
      studies in which the criteria for an ideal model of panic are tested for the 35%
      CO2 challenge. Apart from an absolute specificity for panic disorder, the
      challenge meets these criteria.

PMID- 9657426
TI  - Post-translational modifications required for coagulation factor secretion and
      function.

PMID- 9657427
TI  - Circulating ICAM-1 and VCAM-1 in peripheral artery disease and
      hypercholesterolaemia: relationship to the location of atherosclerotic disease,
      smoking, and in the prediction of adverse events.
AB  - We examined the relationship of soluble intercellular adhesion molecule-1 (sICAM
      1) and vascular cell adhesion molecule-1 (sVCAM-1) with smoking and
      hypercholesterolaemia in peripheral artery disease (PAD). Serum samples were
      obtained from 119 patients with objectively-proven PAD, 39 patients with
      hypercholesterolaemia but asymptomatic for PAD, and 132 age and sex matched
      asymptomatic controls. Using ELISAs, we found increased sICAM-1 and sVCAM-1 (both
      p <0.01) in the patients with PAD relative to the controls, but no significant
      change in patients with hypercholesterolaemia. However, the effect for sVCAM-1
      was lost when smoking was entered as a covariate. Only sICAM-1 was higher in
      patients with PAD in the femoral/iliac arteries compared to the carotid arteries
      (p <0.05). In a 39-month follow-up of 112 patients with PAD, increased ICAM-1
      weakly (univariate p <0.05) predicted those 57 whose disease progressed (i.e. to
      end points such as myocardial infarction and arterial surgery). However, high
      fibrinogen was a much better (univariate p = 0.001, multivariate p <0.05)
      predictor of disease progression. We suggest (i) that increased levels of sVCAM-1
      in atherosclerosis are due to smoking, (ii) that increased sICAM-1 is independent
      of this risk factor, (iii) that both these changes are independent of
      hypercholesterolaemia, and (iv) that increased sICAM-1 is a weak predictor of
      disease progression in peripheral atherosclerosis.

PMID- 9657428
TI  - A novel mutation in intron K of the PROS1 gene causes aberrant RNA splicing and
      is a common cause of protein S deficiency in a UK thrombophilia cohort.
AB  - In the course of investigating the molecular basis of protein S deficiency in 31
      index cases with thrombophilia, we identified seven kindred where the underlying
      defect was a novel A to G transition 9 bp upstream of exon 12 in intron K of the
      PROS1 gene. In all but one case, the mutation caused type I deficiency. One
      individual had type III deficiency. While ectopic transcript analysis using the
      BstXI dimorphism in exon 15 failed to detect a transcript from the mutated
      allele, analysis of transcripts spanning exons 11 and 12 revealed a minor mRNA
      species. Sequencing confirmed the mutation created a new RNA acceptor site
      introducing 8 nucleotides of intronic sequence into the mature mRNA. Haplotype
      analysis of the defective PROS1 alleles in six families revealed the same
      haplotype in all affected individuals suggesting the presence of a common
      ancestor. Six of the fourteen relatives with the mutation experienced at least
      one venous thrombotic event strongly supporting the association of the mutation
      with venous thrombosis.

PMID- 9657429
TI  - Predictive value of plasma thrombomodulin in preeclampsia and gestational
      hypertension.
AB  - In a prospective longitudinal study, 130 primigravidae at risk for preeclampsia
      were examined and plasma sampling performed in 45 of them. Plasma thrombomodulin
      (pTM) was sequentially measured at weeks 12, 24 and 32 of gestation and after
      delivery in 20 primigravidae who developed either mild preeclampsia (n = 8) or
      gestational hypertension (n = 12) between weeks 32 and 39 of gestation and in 25
      (age-matched) primigravidae who had uneventful pregnancies. pTM elevations were
      not observed until week 32 in uneventful pregnancies, but were present by week 24
      (p = 0.002) in patients who later developed hypertensive complications. A net
      individual pTM increase > or = 4.2 ng/ml between weeks 12 and 24 (more than 8
      times that of normotensive primigravidae) and/or pTM level > or = 47.5 ng/ml at
      week 32 predicted the development of hypertensive complications with 80%
      accuracy. Serial pTM determinations can be useful to select pregnancies who may
      benefit from early pharmacological intervention.

PMID- 9657430
TI  - Elevation of serum thrombopoietin precedes thrombocytosis in Kawasaki disease.
AB  - Kawasaki disease (KD) is an acute systemic vasculitis causing coronary arterial
      aneurysms and myocardial infarction in young children. Prominent thrombocytosis
      with increased megakaryocytes develops during the convalescent period. To clarify
      the mechanisms of thrombocytosis, we studied serum levels of thrombopoietin (TPO)
      and other thrombopoietic cytokines in 40 patients with KD (149 samples) and 106
      age-matched controls using ELISA. TPO values in the controls were 1.94 +/- 0.69
      fmol/ml (mean +/- SD) with a 95% reference interval of 0.85 to 3.27 fmol/ml. In
      the first week of KD, platelet counts were normal but TPO values increased
      (approximately 15.5 fmol/ml). TPO levels peaked on day 6 +/- 2 at 5.94 +/- 2.64
      fmol/ml and then fell gradually. When platelet counts peaked in the second to
      third weeks, TPO levels were still high or comparable with the controls. TPO
      levels in KD patients with normal platelet counts were significantly higher than
      control levels. Interleukin (IL)-6 levels in the first week rose, but neither IL
      11 nor leukemia inhibitory factor was detectable. These results suggest that TPO
      contributes to thrombocytosis in KD in conjunction with IL-6 and TPO production
      may be enhanced during the acute phase.

PMID- 9657431
TI  - The diagnostic value of thrombopoietin level measurements in thrombocytopenia.
AB  - It has been reported that blood trombopoietin (TPO) levels can discriminate
      between thrombocytopenia due to increased platelet destruction and decreased
      platelet production. With our TPO ELISA and a glycocalicin ELISA we analysed a
      large group of patients in detail and could confirm and amplify the above notion
      in detail. TPO levels were determined in plasma from 178 clinically and
      serologically well-defined thrombocytopenic patients: 72 patients with idiopathic
      autoimmune thrombocytopenia (AITP), 29 patients with secondary AITP, 5 patients
      with amegakaryocytic thrombocytopenia and 72 patients who suffered from various
      diseases (46 in whom megakaryocyte deficiency was not and 26 in whom it was
      expected). In addition, we measured the level of glycocalicin as a marker of
      total body mass of platelets. In all patients with primary AITP and secondary
      AITP, TPO levels were within the normal range or in some (n = 7) cases only
      slightly increased. The level of glycocalicin was not significantly different
      from that of the controls (n = 95). The patients with amegakaryocytic
      thrombocytopenia had strongly elevated TPO levels and significantly decreased
      glycocalicin levels. Similarly, among the 72 thrombocytopenic patients with
      various disorders, elevated TPO levels were only found in patients in whom
      platelet production was depressed. The mean level of glycocalicin in these
      patients was decreased compared to that in controls and patients with AITP, but
      was not as low as in patients with amegakaryocytic thrombocytopenia. In
      conclusion, all patients with depressed platelet production had elevated levels
      of circulating TPO, whereas the TPO levels in patients with an immune-mediated
      thrombocytopenia were mostly within the normal range. Therefore, measurement of
      plasma TPO levels provides valuable diagnostic information for the analysis of
      thrombocytopenia in general. Moreover, treatment with TPO may be an option in
      AITP.

PMID- 9657432
TI  - Evaluation of thrombopoiesis in thrombocytopenic disorders by simultaneous
      measurement of reticulated platelets of whole blood and serum thrombopoietin
      concentrations.
AB  - To evaluate thrombopoiesis in thrombocytopenic disorders, we simultaneously
      determined reticulated platelet counts in whole blood by FACScan flow cytometry
      and serum thrombopoietin (TPO) concentrations by a sensitive sandwich ELISA. The
      subjects were 40 healthy volunteers and 45 thrombocytopenic patients. In
      idiopathic thrombocytopenic purpura (ITP), the percentage of reticulated
      platelets was significantly elevated (5.61 +/- 2.02%: mean +/- SD) relative to
      normal controls (2.17 +/- 0.90%), but serum TPO concentrations (1.91 +/- 1.27
      fmol/l) did not differ significantly from the normal range (1.43 +/- 0.62
      fmol/l). The patients with aplastic anemia (AA) had decreased reticulated
      platelet counts and markedly increased serum TPO concentrations (13.65 +/- 10.64
      fmol/l). In thrombocytopenic patients with liver cirrhosis (LC), the absolute
      number of reticulated platelets (1.65 +/- 1.11 x 10(9)/l) decreased similarly
      that in AA. However, serum TPO concentrations (1.38 +/- 0.50 fmol/l) did not
      increase in contrast to AA. Our findings suggested a possible dual mechanism of
      thrombocytopenia in LC; that is, thrombocytopenia in LC results from the
      decreased TPO production primarily in the liver adding to an increase in platelet
      sequestration in the spleen.

PMID- 9657433
TI  - Significant correlations between tissue factor and thrombin markers in trauma and
      septic patients with disseminated intravascular coagulation.
AB  - To determine the role of plasma tissue factor on disseminated intravascular
      coagulation (DIC) in trauma and septic patients, and also to investigate the
      relationships between tissue factor and various thrombin markers, we made a
      prospective cohort study. Forty trauma patients and 20 patients with sepsis were
      classified into subgroups according to the complication of DIC. Plasma tissue
      factor antigen concentration (tissue factor), prothrombin fragment F1+2 (PF1+2),
      thrombin antithrombin complex (TAT), fibrinopeptide A (FPA), and D-dimer were
      measured on the day of admission (day 0), and on days 1, 2, 3, and 4 after
      admission. The levels of plasma tissue factor in the DIC group were more elevated
      than those of the non-DIC group in both the trauma and the septic patients. In
      patients with sepsis, tissue factor levels on days 0 through 4 in the non-DIC
      group showed markedly higher values than those in the control patients (135 +/- 8
      pg/ml). Significant correlations between tissue factor and PF1+2, TAT, FPA, and D
      dimer were observed in the DIC patients, however, no such correlations were found
      in the non-DIC patients. These results suggest that elevated plasma tissue factor
      in patients with trauma and sepsis gives rise to thrombin generation, followed by
      intravascular coagulation.

PMID- 9657434
TI  - Low-dose oral vitamin K reliably reverses over-anticoagulation due to warfarin.
AB  - BACKGROUND: Patients receiving long-term warfarin frequently develop asymptomatic
      excessive prolongation of their international normalized ratio (INR) results. The
      most appropriate management strategy in these patients is unknown. This
      prospective cohort study was designed to address whether 1 mg of oral vitamin K
      effectively reduces the INR value of such patients. METHODS: A prospective cohort
      study was performed in two tertiary care teaching hospitals, in which 62 patients
      receiving warfarin who had INR values between 4.5 and 10.0 received 1 mg of oral
      vitamin K. All patients had daily INR values and clinical assessments performed.
      RESULTS: The mean INR value at presentation was 5.79 (95% confidence interval
      (CI) 5.48 to 6.09, range 4.5 to 9.5). Sixteen hours after receiving the 1 mg of
      oral vitamin K, the mean INR was 2.86 (95% CI 2.50 to 3.23). On the second and
      third days after vitamin K, the mean INR values were 2.20 (1.93 to 2.47) and 2.14
      (1.85 to 2.44), respectively. No adverse events or bleeding complications were
      observed. In three patients (6%) the INR value rose between the time of vitamin K
      administration and the next INR determination; two patients received a further 2
      mg dose of subcutaneous vitamin K. CONCLUSIONS: In patients receiving warfarin
      who have asymptomatic excessive prolongations in their INR results, 1 mg of oral
      vitamin K reliably reduces the INR to the therapeutic range within 24 h. This
      therapy is more convenient, less expensive, and might be safer than parenteral
      vitamin K. Thus, it should be considered in all non-bleeding patients receiving
      warfarin, who present with INR results of 4.5 to 9.5.

PMID- 9657435
TI  - Increased potency and decreased elimination of lamifiban, a GPIIb-IIIa
      antagonist, in patients with severe renal dysfunction.
AB  - Activation of the platelet membrane receptor glycoprotein (GP) IIb-IIIa is
      essential for thrombus formation. The novel nonpeptide GPIIb-IIIa antagonist,
      lamifiban, represents a promising approach for antiplatelet therapy in patients
      with cardiovascular disease. Since renal impairment frequently occurs in these
      patients, we designed a phase I study to assess the tolerability,
      pharmacodynamics and pharmacokinetics of lamifiban in patients with renal
      impairment. Four healthy volunteers (Group 1) with creatinine clearance (CLCR)
      >75 ml/min, eight patients (Group 2) with mild to moderately impaired renal
      function (CLCR 30-74 ml/min) and eight patients (Group 3) with severe renal
      impairment (CLCR 10-29 ml/min) were studied. They received stepwise increased
      doses of lamifiban intravenously (i.v.). There was a linear relationship between
      the systemic clearance of the drug and renal function (R2 = 0.86). The mean
      plasma concentration required for half-maximal inhibition of thrombin-receptor
      agonist peptide (TRAP) induced platelet aggregation (EC50) ex vivo was 21, 28 and
      11 ng/ml in Groups 1, 2 and 3. The patients in Group 3 were sensitized to the
      antiplatelet effect allowing an 18-fold dosage reduction without compromising the
      pharmacodynamics. In conclusion, the decreased clearance of lamifiban may act in
      concert with increased potency of the drug in patients with severe renal
      impairment, and the drug dosage should be reduced accordingly.

PMID- 9657436
TI  - Polymorphism of the platelet glycoprotein IIIa gene in patients with coronary
      stenosis.
AB  - Based on genetic variability, structural differences in the glycoprotein IIb/IIIa
      platelet receptor for adhesive proteins result in individual differences in the
      thrombogenicity of platelets. Recent studies suggest a controversial association
      between a genetic polymorphism of the glycoprotein IIIa gene (PlA2) and the risk
      of coronary artery disease. In our study, the prevalence of the PlA2 allele in a
      group of patients undergoing percutaneous coronary revascularization was 37%, a
      value significantly higher than in controls [13%, odds ratio (OR) = 3.93, 95% CI,
      1.84 to 8.53] suggesting a significant association between this polymorphism and
      documented coronary stenosis, which is strongest among <60 years old patients (OR
      = 12.30, 95% CI, 2.98 to 70.93). This polymorphism represents an inherited risk
      factor for severe cardiovascular disease due to coronary occlusion.

PMID- 9657438
TI  - Characterization of a factor VII molecule carrying a mutation in the second
      epidermal growth factor-like domain.
AB  - A missense mutation at codon 100 in the second epidermal growth factor-like
      domain, resulting in Gln100-->Arg, was detected in 19 out of 21 available
      severely factor VII (FVII) deficient patients in Norway. Seventeen patients were
      homozygous, and the two remaining were compound heterozygotes. In the homozygous
      patients, FVII antigen was measured to 10-28%, and activity to 0.6-6.5% of that
      in normal pooled plasma. Recombinant FVII containing the mutation was expressed
      transiently in CHO cells to a mean antigen level of 57% of the wild type FVII
      protein, and with a specific activity of 6% of wild type. The mutant protein had
      a 14-fold reduction in affinity for tissue factor (TF), whereas binding of FX
      seemed unaffected. In line with the experimental data, molecular modelling of the
      mutation based on the coordinates of the tissue factor/FVIIa complex showed that
      substituting arginine for glutamine disrupts the interface between the catalytic
      and second epidermal growth factor-like domains.

PMID- 9657437
TI  - Comparison of a synthetic antithrombin III-binding pentasaccharide and standard
      heparin as an adjunct to coronary thrombolysis.
AB  - The effects on alteplase-induced thrombolysis of the synthetic ATIII-binding
      pentasaccharide SR90107A/ORG 31540 (synthetic pentasaccharide, SP) and of
      standard heparin (SH) were compared in a copper coil model of coronary artery
      thrombosis in 6 groups of 10 dogs. After 1 h of occlusion, all animals received
      intravenously alteplase and aspirin, and were randomly assigned to a 2 h infusion
      of either saline, or one of two doses of SH (100 IU/kg bolus plus 50 IU/kg/h
      infusion, or 200 IU/kg bolus plus 100 IU/kg/h infusion), or one of three doses of
      SP (100 nmol/kg bolus plus 50 nmol/kg/h infusion, 200 nmol/kg bolus plus 100
      nmol/kg/h infusion, or 400 nmol/kg bolus plus 200 nmol/kg/h infusion). Coronary
      angiography was performed every 10 min for 4 h. Appropriate doses of SP and SH
      enhanced alteplase-induced thrombolysis to a similar extent. In contrast, SP was
      devoid of any anti-IIa activity or aPTT prolongation.

PMID- 9657439
TI  - Identification of a glucocorticoid response element in the human gamma chain
      fibrinogen promoter.
AB  - The effect of the synthetic glucocorticoid hormone dexamethasone on human gamma
      chain fibrinogen gene expression was examined. The whole promoter region of 3.8
      kb of this gene and progressive 5'-deletions were inserted into a promoterless
      expression vector, upstream of the luciferase gene and transiently transfected
      into the human hepatoma HepG2 cells, in the presence or in the absence of
      dexamethasone stimulation. Deletion analysis allowed to identify a region located
      between -1359 and -954 bp upstream from the transcription start site, involved in
      hormone inducibility. On the basis of a computer-assisted analysis, a putative
      GRE was found in this region at bases -1116 to -1102. Specific point mutations
      eliminating this putative GRE led to complete loss of glucocorticoid
      inducibility, thus indicating its functional role. Binding of the rat
      glucocorticoid receptor to this site was demonstrated by mobility-shift assays.

PMID- 9657440
TI  - New splicing mutations in the human factor XIIIA gene, each producing multiple
      mutant transcripts of varying abundance.
AB  - Coagulation factor XIII, a transglutaminase which stabilises blood clots by
      covalently cross-linking fibrin, is essential for normal haemostasis. FXIII
      deficiency results in a life-long bleeding disorder with added complications in
      wound healing and tissue repair. Sequence changes in the human FXIIIA gene,
      largely missense mutations, are primarily responsible for inherited FXIII
      deficiency. We have carried out molecular analysis of the FXIIIA gene in two
      unrelated FXIII deficient individuals and identified three splice site mutations;
      a g-->a at the exon 6 acceptor splice site, a g-->a at the exon 7 donor splice
      site and a coding sequence T-->G at the exon 8 donor splice site. We have also
      examined the FXIIIA mRNA in these patients and find that each mutation gives rise
      to multiple transcripts which vary in their relative abundance. The precise
      molecular mechanisms which result in these variant transcripts, and their
      relative abundance in our FXIII deficient patients, are discussed.

PMID- 9657441
TI  - Inhibition of thrombin-catalyzed factor V activation by bothrojaracin.
AB  - We have previously identified and characterized a potent and specific thrombin
      inhibitor, isolated from Bothrops jararaca, named bothrojaracin. Bothrojaracin
      interacts with the two positively charged recognition sites of thrombin referred
      to as exosite 1 and exosite 2, whereas it does not interact with the thrombin
      active site. Consequently, bothrojaracin inhibits thrombin-induced fibrinogen to
      fibrin conversion and platelet activation, without inhibition of thrombin
      catalyzed cleavage of small synthetic substrates. In the present study, we show
      that bothrojaracin exerts an anticoagulant effect in plasma, illustrated by the
      prolongation of the aPTT. Using purified proteins, we observed that the
      anticoagulant effect of bothrojaracin was not only due to the inhibition of
      fibrinogen to fibrin conversion, but in addition to the inhibition of factor V
      activation by thrombin. Bothrojaracin decreased the rate of thrombin-catalyzed
      proteolysis of factor V and concurrently the generation of factor Va cofactor
      activity measured in a prothrombinase assay. We compared the effect of
      bothrojaracin with that of ligands binding specifically exosite 1 (hirudin C
      terminal peptide SH54-65) or exosite 2 (heparin, prothrombin fragment 2). SH54-65
      delayed thrombin catalyzed factor V activation whereas heparin or prothrombin
      fragment 2 did not. The thrombin derivatives beta- and gamma-thrombin, which are
      defective in their exosite 1, but present with a normally exposed exosite 2, had
      a reduced capacity to activate factor V, which was not further impaired by the
      exosite 2 ligands, bothrojaracin, heparin or prothrombin fragment 2. Altogether,
      our results provide further insight into the anticoagulant effect of
      bothrojaracin showing that it is a potent inhibitor of the feedback activation of
      factor V by thrombin, and thus of the up-regulation of its own production by
      thrombin. Inhibition of thrombin-catalyzed factor V activation by bothrojaracin
      is mainly mediated through the interaction of the inhibitor with thrombin exosite
      1, whereas contribution of the interaction with exosite 2 does not appear to play
      a direct role in factor V recognition by thrombin.

PMID- 9657442
TI  - Aging and venous thromboembolism influence the pharmacodynamics of the anti
      factor Xa and anti-thrombin activities of a low molecular weight heparin
      (nadroparin).
AB  - Venous thromboembolism may be efficiently treated by one single daily
      administration of a high dose of low molecular weight heparin (LMWH). The present
      study investigates if the physiological deterioration of renal function
      associated with normal aging or the presence of an acute venous thromboembolism
      influences the pharmacodynamic pattern of the anti-factor Xa and anti-thrombin
      activities. Three groups of 12 subjects were investigated. The first 2 groups
      were composed of healthy volunteers differing by age (25 +/- 4 and 65 +/- 3 yrs)
      and creatinine clearance (114 +/- 15 and 62 +/- 6 ml x min(-1)). The third group
      was composed of patients hospitalized for deep vein thrombosis, having a mean age
      of 65 +/- 11 yrs and creatinine clearance of 76 +/- 8 ml x min(-1). Nadroparin
      was administered subcutaneously once daily at the dose of 180 anti-factor Xa
      IU.kg(-1) for 6 to 10 days. Serial sampling on day 1 and on the last day of
      administration (day n) allowed the pharmacodynamic parameters of the anti-factor
      Xa and anti-thrombin activities to be compared at the beginning and at the end of
      the treatment. The main findings were the following: (1) After repeated
      administration, a significant accumulation of the anti-factor Xa activity was
      observed in the healthy elderly and in the patients but not in the healthy young
      subjects (accumulation factor: 1.3). There was no evidence of accumulation of
      anti-thrombin activity; (2) There were significant correlations between the
      clearance of creatinine and the clearance of the anti-factor Xa activity but not
      with that of the anti-thrombin activity; (3) In the patients, the clearance of
      the anti-factor Xa and of the anti-thrombin activities were 1.4 and 2 times
      higher respectively than those calculated in the healthy elderly; (4) The mean
      ratio of the of anti-factor Xa and anti-thrombin clearances was close to 2 in the
      healthy subjects but equal to 5.4 in the patients. These results suggest that the
      mechanisms involved in the clearance of polysaccharide chains which support the
      anti-thrombin activity are different from those of the anti-factor Xa activity
      and that the enhanced binding properties of plasma proteins to unfractionated
      heparin reported in patients presenting an acute venous thromboembolism also
      exists for LMWH, predominantly for the anti-thrombin activity.

PMID- 9657443
TI  - Activated protein C sensitivity, protein C, protein S and coagulation in normal
      pregnancy.
AB  - A prospective study of activated protein C sensitivity, protein C, protein S, and
      other coagulation factors in 239 women during normal pregnancy was carried out.
      Protein C activity appeared unaffected by gestation, although an elevation of
      protein C activity was observed in the early puerperium. A fall in total and free
      protein S with increasing gestation was observed. Activated protein C sensitivity
      ratio (APC:SR) showed a progressive fall through pregnancy. This fall correlated
      with changes in factor VIIIc, factor Vc and protein S. 38% of subjects, with no
      evidence of Factor V Leiden or anticardiolipin antibodies, showed a low APC:SR
      (APC:SR <2.6) in the third trimester of pregnancy. Aside from a significant
      reduction in birth weight, no difference in pregnancy outcome was observed
      between these subjects and those with a normal APC:SR. Activated protein C
      sensitivity ratio, modified by pre-dilution of patient samples with factor V
      depleted plasma, showed no consistent trend with gestation.

PMID- 9657444
TI  - Regulation of gelatinase activity in mice with targeted inactivation of
      components of the plasminogen/plasmin system.
AB  - To investigate a potential physiological role of the plasminogen/plasmin system
      in activation of the matrix metalloproteinase (MMP) system, the distribution of
      latent and active MMP-2 (gelatinase A) or MMP-9 (gelatinase B) was monitored in
      aorta extracts and in serum-free conditioned cell culture medium obtained from
      wild-type (WT) mice and from mice with deficiency of tissue-type plasminogen
      activator (t-PA(-/-)), urokinase-type plasminogen activator (u-PA(-/-)),
      plasminogen activator inhibitor-1 (PAI-1(-/-)) or plasminogen (Plg(-/-)). In
      aorta extracts, the contribution of active MMP-2 to the total MMP-2 level ranged
      between 7 and 16% for the different genotypes, whereas active MMP-9 was not
      detected. The contribution of active 58 kDa MMP-2 to the total MMP-2 level
      (active plus latent) ranged between 14 and 29% (mean of 3 experiments) for
      fibroblasts of the different genotypes, and between 18 and 32% for smooth muscle
      cells, and was relatively constant in time (7-72 h). The contribution of active
      83 kDa MMP-9 to the total MMP-9 level ranged between 15 and 29% for fibroblasts
      of the different genotypes and was relatively constant in time (24-72 h);
      corresponding values were 17 to 57% for smooth muscle cells, with the exception
      of Plg(-/-) smooth muscle cells which had undetectable levels of active MMP-9.
      Addition of plasmin(ogen) to the cell culture medium of fibroblasts did not
      significantly affect the distribution of active and latent MMP-2, but resulted in
      an approximately two-fold enhancement of the contribution of active MMP-9. In
      macrophages of Plg(-/-) mice, active MMP-9 was detected only when the cells were
      cultured in the presence of plasminogen. These data indicate that activation of
      proMMP-2 occurs independently of the physiological plasminogen activators and of
      plasmin(ogen) in all the cell types evaluated. Activation of proMMP-9 was
      enhanced in the presence of plasmin(ogen), but active MMP-9 was also detected in
      fibroblasts of Plg(-/-) mice, indicating that in vivo activation may occur via
      plasmin(ogen)-independent mechanisms.

PMID- 9657445
TI  - Neutrophils rolling on immobilised platelets migrate into homotypic aggregates
      after activation.
AB  - Interactions between platelets and leucocytes are implicated in the pathology of
      thrombotic vascular disease. Using a flow-based adhesion assay we have
      investigated a novel route for the formation of neutrophil aggregates on the
      surface of immobilised activated platelets. Neutrophils perfused over a platelet
      monolayer formed numerous rolling attachments but rapidly stopped and spread
      after the superfusion of N-formyl-methionyl-leucyl-phenylalanine or platelet
      activating factor (both at 10(-7) M). Subsequent integrin-mediated migration
      across the platelet monolayer enabled formation of homotypic neutrophil
      aggregates, which was significant within 2.5 min of receipt of either stimulus.
      Aggregates increased in size with time and had an average projected area of
      approximately 500 microm2 after 10 min. Increasing size was correlated with an
      increasing tendency for movement downstream and large aggregates sometimes
      tumbled in that direction. The formation and stability of homotypic aggregates
      was dependent on several adhesive mechanisms. Antibody blockade demonstrated that
      interactions involving CD11a/CD18 and ICAM-3, between alpha(v)beta3-integrin and
      CD31 and between L-selectin and an unidentified counter-ligand were all required
      for the complete aggregatory response. Furthermore, blockade of L-selectin
      allowed initial aggregation which then reversed, suggesting that this receptor
      might regulate the interactions between other adhesion molecules that directly
      supported cell-cell adhesion. We propose that this novel route for leucocyte
      aggregation could promote vascular occlusion in thrombotic vessels or at distal
      sites in the event of embolisation.

PMID- 9657447
TI  - On the mechanism of plasmin-induced aggregation of human platelets: implication
      of secreted von Willebrand factor.
AB  - Plasmin triggers a strong metabolic activation in human platelets, leading to
      shape change and granule exocytosis. However, its capacity to induce cell
      aggregation remains discussed and, when observed, this aggregation is preceded by
      a remarkable lag phase. We have thus investigated the effect of plasmin on the
      adhesive proteins which can be secreted by isolated platelets and mediate cell-to
      cell interactions, but are also substrates for the enzyme. Immunoblot analysis of
      fibrinogen (Fg), thrombospondin-1 (TSP-1), fibronectin (Fn) and von Willebrand
      factor (vWf) was performed on extracts of platelets exposed under stirring to
      increasing concentrations of plasmin for up to 10 min at 37 degrees C. Under
      conditions leading to formation of large aggregates, Fg, Fn and TSP-1 are
      extensively degraded concomitantly with their secretion, and readily lost from
      the surface of aggregated cells. Part of the monomers in the platelet vWf are
      cleaved during secretion into two main fragments with Mr approximately 180,000
      and approximately 145,000. However, multimer distribution analysis shows only a
      slight decrease in the very high molecular weight multimers, and most of the
      fragmented as well as intact vWf remains associated with the platelet surface
      when aggregation is maximal. That indeed vWf largely supports plasmin-induced
      aggregation is suggested by the observation that platelets from a patient with
      type 3 von Willebrand's disease, who totally lacks vWf, show little aggregation
      in response to the enzyme. Finally, plasmin-induced aggregation can be totally
      inhibited by antagonists of the alpha(IIb)beta3 integrin. The present study thus
      indicates a major role for secreted vWf in platelet aggregation induced by
      plasmin, through its likely interaction with the multifunctional receptor
      alpha(IIb)beta3.

PMID- 9657446
TI  - Difference of (Ca2+)i movements in platelets stimulated by thrombin and TRAP: the
      involvement of alpha(IIb)beta3-mediated TXA2 synthesis.
AB  - This study investigated the difference of [Ca2+]i movement in platelets in
      response to thrombin and TRAP. The involvement of alpha(IIb)beta3 in this
      signaling was also studied. Stimulation of platelets with thrombin at 0.03 U/ml
      caused platelet aggregation and a two-peak increase in [Ca2+]i. The second peak
      of [Ca2+]i, but not the first peak was abolished by the inhibition of platelet
      aggregation with alpha(IIb)beta3 antagonists or by scavenging endogenous ADP with
      apyrase. A cyclooxygenase inhibitor, aspirin, and a TXA2 receptor antagonist, BM
      13505, also abolished the second peak of [Ca2+]i but not the first peak, although
      these regents did not inhibit aggregation. Under the same assay conditions,
      measurement of TXB2 demonstrated that alpha(IIb)beta3 antagonists and aspirin
      almost completely inhibited the production of TXB2. In contrast to thrombin
      stimulation, TRAP caused only a single peak of [Ca2+]i even in the presence of
      platelet aggregation, and a high level of [Ca2+]i increase was needed for the
      induction of platelet aggregation. The inhibition of aggregation with
      alpha(IIb)beta3 antagonists had no effect on [Ca2+]i change and TXB2 production
      induced by TRAP. Inhibition studies using anti-GPIb antibodies suggested that
      GPIb may be involved in the thrombin response, but not in the TRAP. Our findings
      suggest that low dose thrombin causes a different [Ca2+]i response and TXA2
      producing signal from TRAP. Endogenous ADP release and fibrinogen binding to
      alpha(IIb)beta3 are responsible for the synthesis of TXA2 which results in the
      induction of the second peak of [Ca2+]i in low thrombin- but not TRAP-stimulated
      platelets.

PMID- 9657448
TI  - The cDNA cloning and molecular characterization of a snake venom platelet
      glycoprotein Ib-binding protein, mamushigin, from Agkistrodon halys blomhoffii
      venom.
AB  - The entire cDNA sequences of a novel snake venom platelet glycoprotein (GP) Ib
      binding protein (BP) composed of an alpha/beta heterodimeric structure, termed
      mamushigin, from Agkistrodon halys blomhoffii were determined, that include the
      leader peptides (21/23 amino acid residues) and mature subunits (136/123 amino
      acid residues). The mature subunits of mamushigin are 37.5% identical, and showed
      a high degree of similarity (37.7-67.5% identity) with the respective subunits of
      group VII C-type lectins (19). The sequences of the leader peptides of the
      mamusigin subunits showed the highest similarity (alpha-73.9/beta-82.6%) with
      those of factor IX/X-BP from Trimeresurus flavoviridis, and the cleavage site
      residue in both proteins was the same Ala(-1). The GPIb-binding specificity of
      mamushigin is strongly supported by several lines of evidence, but mamushigin can
      directly aggregate normal platelets, similar to alboaggregin-B (AL-B) (1). This
      differs from other GPIb-BP's. In mamushigin-treated platelets, serotonin was not
      released, and flow cytometric analysis using a monoclonal antibody PAC-1 totally
      excluded platelet GPIIb/IIIa activation. Mamushigin enhanced platelet aggregation
      at low-shear stress, and this effect totally disappeared in the presence of GPIb
      receptor blockers specific for von Willebrand factor binding, but not by
      GPIIb/IIIa-receptor blockers. At high-shear stress, mamushigin blocked platelet
      aggregation in a dose-dependent manner, as seen with other GPIb-BP's. This paper,
      therefore, describes the cDNA cloning and molecular characterization of
      mamushigin which has a different effect on platelet aggregation under different
      shear stress.

PMID- 9657449
TI  - Nitric oxide and prostacyclin are involved in antithrombotic action of captopril
      in venous thrombosis in rats.
AB  - The long-term administration of captopril to patients with a left ventricular
      dysfunction after myocardial infarction reduces the rate of recurrent coronary
      thrombosis. Thus, in the present study we investigated the influence of
      angiotensin-converting enzyme inhibitors (ACE-Is) on experimental venous
      thrombosis in normotensive rats and the involvement of NO and PGI2 in this
      effect. Animals were treated with captopril (1.5, 5 or 25 mg/kg twice daily,
      CAP), enalapril (15 mg/kg once daily, ENA) or distilled water for 10 days, per
      os. After ligation of the vena cava the thrombus weight decreased in both CAP and
      ENA treated rats. The effect was most pronounced in animals given the highest
      dose of CAP (p<0.0001 vs. control) and was significantly stronger than observed
      in ENA treated animals (CAP vs. ENA p<0.01). The mean blood pressure measured by
      the "tail cuff" method and platelet aggregation were not altered by either of the
      ACE-Is. The antithrombotic activity of CAP was reduced by indomethacin (2.5
      mg/kg, s.c.) and independently by the NO-synthase inhibitor N(G)-nitro L-arginine
      methyl ester (3 mg/kg i.v. bolus + 3 mg/kg/h i.v. infusion, L-NAME). In the
      latter case CAP regained its antithrombotic properties in rats pretreated with L
      Arginine (300 mg/kg i.v. + 300 mg/kg/h i.v.) before administration of L-NAME
      (p<0.05 vs. control). Moreover, the concomitant administration of indomethacin
      and L-NAME failed to completely abolish the antithrombotic action of captopril.
      Similar effects were observed in respect to the incidence of venous thrombosis.
      Our study documents a novel and important effect of ACE-Is on the vein thrombotic
      process and demonstrates the involvement of NO and PGI2 in this phenomenon.

PMID- 9657450
TI  - Platelet dysfunction as the cause of spontaneous bleeding in two haemophilic
      patients taking HIV protease inhibitors.

PMID- 9657451
TI  - Prothrombin 20210A polymorphism and third generation oral contraceptives--a case
      report of coeliac axis thrombosis and splenic infarction.

PMID- 9657452
TI  - Protein C gene polymorphism and hypertensive cerebrovascular disease in Japanese.

PMID- 9657453
TI  - On the release of von Willebrand factor from endothelial cells after venous
      occlusion.

PMID- 9657454
TI  - SimpliRED D-dimer assay: comparability of capillary and citrated venous whole
      blood, between-assay variability, and performance of the test for exclusion of
      deep vein thrombosis in symptomatic outpatients.

PMID- 9657455
TI  - Monocyte tissue factor (CD142) and Mac-1 (CD11b) are increased in septic
      patients.

PMID- 9657456
TI  - Validation of predicted total body water and extracellular water by multi
      frequency impedance in young Indonesian adults.
AB  - To investigate the validity of the prediction of body water compartments by multi
      frequency impedance in Indonesians, 42 adults (19 males and 23 females) were
      recruited in Jakarta, the capital of Indonesia. Extracellular water (ECW) and
      total body water (TBW) were measured with dilution techniques and predicted from
      body impedance at 1 and 100 kHz, respectively, using prediction formulas
      developed in a Dutch population. Furthermore, body weight, body height and body
      density were measured and as a measure of body build TBW/height and ECW/height
      were calculated. Percent ECW of body weight in both males (26 +/- 3%) and females
      (23 +/- 2%) was higher compared to the Dutch reference population, and also the
      body water distribution (ECW/TBW) was higher (0.46 +/- 0.04) compared to the
      reference population. TBW/height and ECW/height appeared to be considerably lower
      in the Indonesian group compared to the reference group, indicating a more
      slender body shape. TBW was overestimated by 1.8 +/- 2.4 and 2.5 +/- 1.3 kg in
      males and females, respectively. ECW was underestimated in males by 0.1 +/- 1.2
      kg and slightly overestimated in females (0.1 +/- 1.0 kg). After corrections for
      differences in body build and body water distribution the bias of the predicted
      TBW was markedly reduced from 2.2 +/- 1.9 to 1.3 +/- 1.8 kg (males and females
      combined). For ECW the bias after correction for body water distribution and body
      build was 0.3 +/- 0.6 kg (males and females combined). It is concluded that multi
      frequency impedance is suitable for the prediction of body water compartments at
      the population level but, due to differences in body build and body water
      distribution, validation in a larger group of Indonesian subjects is needed to
      avoid systematic prediction errors.

PMID- 9657457
TI  - Study design of a total reference diet for a population in Northern Italy.
AB  - A market based of 91 food items was purchased in Northern Italy, based on a list
      taken from a food survey previously conducted in the same area. The food items
      from the survey were grouped into 14 categories. Food samples were collected,
      homogenized, and frozen for the analysis of both the nutrient content and the
      levels of mineral contaminants. The study design and decision processes behind
      the choice of type and quantity of each food are explained. The relative
      quantities of each food group were compared with those from two similar studies.
      Finally, energy, nutrients, and mineral contaminants obtained by direct analysis
      were compared with the calculations given on the food composition tables. The
      comparison between the analyzed and calculated data only showed marked
      differences in phosphorus, sodium, potassium, and copper intakes.

PMID- 9657458
TI  - Fat sources in the Belgian diet.
AB  - Food consumption data from the Belgian Interuniversity Research on Nutrition and
      Health study (n = 11,302) were analyzed with regard to fat intake. Intakes of
      macronutrients were compared between several subgroups in the population. The
      major objective was to quantify the contribution of food groups and individual
      food items to the intake of total fat, polyunsaturated (PUFA), monounsaturated
      (MUFA) and saturated (SFA) fat in the Belgian diet. These results are compared to
      nutritional guidelines and Italian, US and Dutch data. Major sources of fat are
      butter (16% of the total intake) and baking margarine (8%). Major sources of SFA
      are butter (24%) and cheese (8%), of MUFA butter (13%) and baking margarine (9%),
      and of PUFA diet margarine (23%) and mayonnaise (11%).

PMID- 9657459
TI  - Fatty acid composition of the Belgian diet: estimates derived from the Belgian
      Interuniversity Research on Nutrition and Health.
AB  - The major objective of this study was to determine the fatty acid composition of
      the Belgian diet. Food consumption data from a large representative sample (n =
      11,302) of the Belgian population between 25 and 74 years of age (BIRNH study)
      were analyzed with regard to the intake of fatty acids. The fatty acid
      composition of the major fat sources in the Belgian diet was determined and used
      to calculate average intakes for fatty acids from C4 to C22. In addition, results
      are compared to other studies and to guidelines for n-3 and n-6 fatty acids.
      Saturated fatty acids provide 17% of the energy intake in the Belgian diet,
      polyunsaturated fatty acids 7%, and monounsaturated fatty acids 14%. The intake
      of total n-6 fatty acids is very high (6 en%), particularly of linoleic acid. The
      intake of n-3 fatty acids is low, only 0.8 en%, which results in a low ratio of n
      3 to n-6 (0.15). The most important sources of n-6 and n-3 fatty acids are
      margarine and meat, respectively.

PMID- 9657460
TI  - Olive oil supplementation in healthy adults: effects in cell membrane fatty acid
      composition and platelet function.
AB  - Ten healthy volunteers were given a daily supplement of 30 g olive oil for 6
      weeks in order to evaluate how it would affect cell membrane composition and
      ultimately platelet function. Fasting blood and cheek cell samples were taken
      before commencing the study, after 21 and 42 days of supplementation and also at
      30 days after finishing the supplement (washout). C18:1n-9 was significantly
      increased (p < 0.01) in platelet and cheek cell phospholipids. Erythrocytes were
      not good markers for C18:1n-9 intake and no significant change was found in this
      tissue. There was a small nonsignificant decrease in platelet phospholipid 20:4n
      6 after the supplementation, in accordance with previously published results.
      C18:1n-9 did not persist in platelet membranes after the volunteers stopped
      consuming the olive oil supplement, but in erythrocytes a significant increase (p
      < 0.05) was found after the washout period. None of these changes in fatty acid
      composition in the different tissues were related to significant changes in serum
      cholesterol-related variables or in clotting factors or adenosine diphosphate
      induced platelet aggregation.

PMID- 9657461
TI  - Influence of different fat emulsions with 10 or 20% MCT/LCT or LCT on
      lipoproteins in plasma of patients after abdominal surgery.
AB  - In patients after elective abdominal surgery, different fat emulsions were used
      to compare their efficacy in total parenteral nutrition and in normalizing plasma
      lipoprotein levels. In five different groups with 5 patients each, half of the
      nonprotein calories were given as medium-chain triglycerides/long-chain
      triglycerides (1:1) or as long-chain triglycerides alone in 10 or 20% fat
      emulsions or as glucose alone in a control group for 7 days. After surgery, an
      initial decrease of all plasma lipoprotein components was followed by a different
      behavior of glyceride-glycerol, cholesterol, phospholipids, and apolipoproteins.
      Glyceride-glycerol in very-low-density lipoproteins and high-density lipoproteins
      is increasing during infusion of fat emulsions and decreasing during overnight
      interruption of infusions. After the 7-day infusion period, there was no
      significant difference in very-low-density lipoprotein glyceride-glycerol as
      compared with the values before different infusions. Low-density lipoprotein
      cholesterol is reaching and exceeding preoperative concentrations between the 4th
      and the 7th day, most during infusion of 10% fat emulsion and especially due to
      an increase of free cholesterol. High-density lipoprotein cholesterol and
      apolipoprotein A-I reach preoperative levels during infusion of fat emulsions but
      not with glucose alone. Higher than preoperative values are reached in
      phospholipids with all fat infusions already on day 4. Abnormal lipoprotein X
      occurred least with the medium-chain/long-chain triglyceride 20% fat-infusion.
      This fat emulsion is suggested as having the best normalizing effect on plasma
      lipoproteins and best tolerance in patients after surgery.

PMID- 9657462
TI  - Hepatic glycogen and lactate handling in dietary obese rats.
AB  - Hepatic balances for glucose and its precursor, lactate, were calculated by
      measuring hepatic blood flows and the arteriovenous differences of these
      metabolites in 2 groups of overweight rats: cafeteria diet-fed rats and post
      cafeteria rats. Obese rats show abnormal hepatic glycogen handling, since they do
      not mobilize all hepatic glycogen stores after 24-hour starvation, in a situation
      in which a lower rate of hepatic glucose output and a higher capacity for lactate
      uptake are attained. The important decrease (about 50%) in the hepatic blood
      flows observed in post-cafeteria rats versus control rats was similar to that
      caused by 24-hour starvation in control animals, suggesting that after withdrawal
      of the cafeteria diet, the liver blood flow of the post-cafeteria rats was
      adapted to the low-food intake in order to make better use of the energy
      consumed. The results also suggest an increased efficiency of hepatic lactate
      uptake in post-cafeteria rats.

PMID- 9657463
TI  - Chronic disease: infectious cause?

PMID- 9657464
TI  - Primary stenting in acute myocardial infarction: the promise and the proof.

PMID- 9657465
TI  - Heparin responsiveness in vitro as a prognostic tool for vascular graft stenosis:
      a tale of two cell types?

PMID- 9657466
TI  - Dispersion of ventricular repolarization: reality? Illusion? Significance?

PMID- 9657467
TI  - Reduced endothelial nitric oxide synthase expression and production in human
      atherosclerosis.
AB  - BACKGROUND: NO regulates vascular tone and structure, platelets, and monocytes.
      NO is synthesized by endothelial NO synthase (eNOS). Endothelial dysfunction
      occurs in atherosclerosis. METHODS AND RESULTS: With a porphyrinic microsensor,
      NO release was measured in atherosclerotic human carotid arteries and normal
      mammary arteries obtained during surgery. eNOS protein expression was analyzed by
      immunohistochemistry. In normal arteries, the initial rate of NO release after
      stimulation with calcium ionophore A23187 (10 micromol/L) was 0.42+/-0.05
      (micromol/L)/s (n=10). In contrast, the initial rate of NO release was markedly
      reduced in atherosclerotic segments, to 0.08+/-0.04 (micromol/L)/s (n=10,
      P<0.0001). NO peak concentration in normal arteries was 0.9+/-0.09 micromol/L
      (n=10) and in atherosclerotic segments, 0.1+/-0.03 micromol/L (n=10, P<0.0001).
      Reduced NO release in atherosclerotic segments was accompanied by marked
      reduction of immunoreactive eNOS in luminal endothelial cells, although specific
      endothelial cell markers (CD31) were present (n=13). Endothelial cells of vasa
      vasorum of atherosclerotic segments, however, remained positive for eNOS, as was
      the endothelium of normal arteries. CONCLUSIONS: In clinically relevant human
      atherosclerosis, eNOS protein expression and NO release are markedly reduced.
      This may be involved in the progression of atherosclerosis.

PMID- 9657468
TI  - Effects of tumor necrosis factor gene polymorphisms on patients with congestive
      heart failure. VEST Investigators for TNF Genotype Analysis. Vesnarinone Survival
      Trial.
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is known to be elevated in
      patients with congestive heart failure (CHF). Two biallelic polymorphisms have
      been identified in the TNF gene locus: one in the promoter region of TNF-alpha
      (TNFA1/2), and the other in the first intron of TNF-beta (TNFB1/2). Both TNFA2
      and TNFB2 alleles are associated with high TNF-alpha production in vitro and
      susceptibility to inflammatory diseases. Given the importance of TNF-alpha in the
      pathogenesis of CHF, we studied the prevalence of TNF gene polymorphisms in CHF
      patients and the correlation of genotypes to in vivo TNF-alpha levels. METHODS
      AND RESULTS: TNFA and TNFB genotypes were determined by the polymerase chain
      reaction-restriction fragment length polymorphism technique. There were no
      differences in the TNF allele frequencies between CHF (n=229; TNFA1/2=0.84/0.16,
      TNFB1/2=0.33/0.67) and control subjects (n=139; TNFA1/2=0.84/0.16,
      TNFB1/2=0.32/0.68). In 211 patients with CHF, circulating levels of TNF-alpha and
      the soluble receptors type I and type II were measured by ELISA: 6.18+/-3.59
      pg/mL, 1768+/-761 pg/mL, and 4484+/-1750 pg/mL, respectively. There were no
      correlations between TNFA or TNFB genotypes and circulating levels of TNF-alpha
      or its soluble receptors in the CHF patients. CONCLUSIONS: Despite their
      association with other inflammatory diseases, neither TNFA nor TNFB polymorphisms
      are related to the presence of CHF or the elevation of circulating TNF-alpha.
      Thus, other factors may be more important in determining the circulating levels
      of TNF-alpha in CHF.

PMID- 9657469
TI  - Randomized comparison of coronary stenting with balloon angioplasty in selected
      patients with acute myocardial infarction.
AB  - BACKGROUND: Although the benefits of primary angioplasty in acute myocardial
      infarction have been demonstrated, several areas for improvement remain.
      Therefore, a prospective randomized trial comparing primary stenting with balloon
      angioplasty in patients with acute myocardial infarction was conducted. METHODS
      AND RESULTS: Patients with acute myocardial infarction were randomly assigned to
      undergo either primary stenting (n=112) or balloon angioplasty (n=115). The
      clinical end points were death, recurrent infarction, subsequent bypass surgery,
      or repeat angioplasty of the infarct-related vessel. The overall mortality rate
      at 6 months was 2%. Recurrent infarction occurred in 8 patients (7%) after
      balloon angioplasty and in 1 (1%) after stenting (P=0.036). Subsequent target
      vessel revascularization was necessary in 19 (17%) and 4 (4%) patients,
      respectively (P=0.0016). The cardiac event-free survival rate in the stent group
      was significantly higher than in the balloon angioplasty group (95% versus 80%;
      P=0.012). CONCLUSIONS: In selected patients with acute myocardial infarction,
      primary stenting can be applied safely and effectively, resulting in a lower
      incidence of recurrent infarction and a significant reduction in the need for
      subsequent target-vessel revascularization compared with balloon angioplasty.

PMID- 9657470
TI  - Vein graft stenosis and the heparin responsiveness of human vascular smooth
      muscle cells.
AB  - BACKGROUND: Vascular smooth muscle cell (VMSC) proliferation is an essential
      component of myointimal hyperplasia, which is implicated in the failure of 30% to
      50% of vascular interventions, such as coronary angioplasty and peripheral vein
      grafting. We have shown that cells derived from stenotic lesions in infrainguinal
      vein grafts were significantly more resistant than controls to growth inhibition
      by heparin. METHODS AND RESULTS: In a prospective study, we correlated
      antiproliferative responses to heparin in vitro with graft patency after 1 year.
      Sixty-two patients with infrainguinal vein grafts were entered into a graft
      surveillance program for > or = 1 year. At operation, saphenous vein segments
      were explanted for VSMC culture. Cell proliferation in response to fetal calf
      serum was later determined in the presence and absence of heparin. In 35 cell
      cultures, including 13 from the above-mentioned patients, [3H]heparin binding was
      also estimated. VSMCs from patients with patent grafts were significantly more
      sensitive to growth inhibition by heparin than cells from patients with stenoses
      (median, 54% versus 20.9%, P<0.001), and [3H]heparin binding was strongly
      correlated with inhibition of proliferation (r=0.81). CONCLUSIONS: Responsiveness
      to heparin in cultured VSMCs is a strong predictor of outcome for infrainguinal
      vein grafts, and reduced sensitivity to heparin is correlated with decreased
      heparin binding. Relative resistance to the antiproliferative action of heparin
      may be a marker for aberrant regulation of VSMC growth.

PMID- 9657471
TI  - Lower expression of neutrophil adhesion molecule indicates less vessel wall
      injury and might explain lower restenosis rate after cutting balloon angioplasty.
AB  - BACKGROUND: The Cutting Balloon is a novel dilatation catheter for coronary
      angioplasty (InterVentional Technologies Inc). It produces longitudinal,
      microsurgical incisions in the vessel wall before the actual dilatation. It is
      assumed that these controlled surgical incisions relieve hoop stress and reduce
      vessel wall injury and eventually restenosis. However, no clinical indicator to
      support the theory of reduced injury has been described. Certain clusters of
      differentiation (eg, CD11, CD18 on the leukocytes) are implicated in leukocyte
      adhesion, increased permeability, and opsonization. Therefore, they might serve
      as clinical indicators of the injury level of the vessels after angioplasty.
      METHODS AND RESULTS: We randomly selected 64 patients with isolated left anterior
      descending coronary artery disease for either Cutting Balloon angioplasty or
      conventional balloon angioplasty. The expression of CD18 and CD11b on the surface
      of neutrophils was determined by flow cytometric analysis. Serum levels of
      soluble intercellular adhesion molecule-1 (sICAM-1) were also measured. The
      expression of both the CD18 and CD11b in the coronary sinus blood gradually
      increased and reached its maximum at 48 hours after angioplasty. The sICAM-1
      levels in the coronary sinus serum also increased after angioplasty. Percentage
      increases of CD18 and CD11b expression and the increase of the sICAM-1 levels at
      48 hours after angioplasty (as ratios to baseline values before angioplasty) were
      less in the Cutting Balloon angioplasty group than in the conventional balloon
      angioplasty group (CD18, 1.10+/-0.05 versus 1.31+/-0.05, P<0.05; CD11b, 1.23+/
      0.06 versus 1.72+/-0.10, P<0.001; sICAM-1, 1.12+/-0.05 versus 1.25+/-0.02,
      P<0.05). In all patients, the late lumen loss at follow-up angiogram positively
      correlated with the increased levels of CD11b (R=0.59, P<0.001) and sICAM-1
      (R=0.38, P<0.05) at 48 hours after angioplasty. CONCLUSIONS: Balloon angioplasty
      upregulated Mac-1 (CD11b/CD18) on the surface of the neutrophils and increased
      sICAM-1 levels in association with late loss increase. These changes were
      significantly smaller in the Cutting Balloon angioplasty group than in the
      conventional balloon angioplasty group. This suggests that Cutting Balloon
      angioplasty may produce less vessel wall injury and, consequently, less
      neutrophil activation, which may account for the lower rate of restenosis.

PMID- 9657472
TI  - Association of remnant lipoprotein levels with impairment of endothelium
      dependent vasomotor function in human coronary arteries.
AB  - BACKGROUND: It remains undetermined whether triglyceride-rich lipoproteins are an
      independent risk factor for atherosclerosis. METHODS AND RESULTS: The correlation
      of responses of coronary arterial diameter (quantitative coronary angiography)
      and coronary blood flow (intracoronary flow wire technique) to intracoronary
      infusion of acetylcholine (10 and 50 microg/min) with coronary risk factors
      including remnant lipoprotein levels was statistically analyzed in 106
      consecutive subjects with normal coronary angiograms. Remnant lipoproteins were
      isolated from fasting blood with an immunoaffinity mixed gel containing anti
      apolipoprotein (apo) A-1 and anti-apoB-100 monoclonal antibodies. In multivariate
      stepwise regression analysis, remnant lipoprotein levels had the most significant
      correlation with abnormal epicardial coronary vasomotor responses to
      acetylcholine infusion, reflected by impaired dilation or constriction of the
      epicardial coronary arteries, and the levels also had an inverse and independent
      correlation with the coronary blood flow increase in response to acetylcholine.
      In a subgroup of 53 consecutive subjects, constrictor responses of epicardial
      coronary diameters to intracoronary infusion of NG-monomethyl-L-arginine (50
      micromol/min for 4 minutes) at baseline, reflecting the presence of coronary
      nitric oxide bioactivity, had an inverse and independent correlation with remnant
      lipoprotein levels by use of multivariate analysis. CONCLUSIONS: Remnant
      lipoprotein levels were independently associated with abnormal endothelium
      dependent vasomotor function in large and resistance coronary arteries in humans,
      indicating that remnant lipoproteins may impair endothelial vasomotor function in
      human coronary arteries. The decrease in coronary nitric oxide bioactivity may be
      responsible in part for the inhibitory effects of remnant lipoproteins.

PMID- 9657473
TI  - Marked reduction in internal atrial defibrillation thresholds with dual-current
      pathways and sequential shocks in humans.
AB  - BACKGROUND: This study tested the ability of sequential shocks delivered through
      dual-current pathways to lower the atrial defibrillation threshold (ADFT)
      compared with a biphasic shock through a standard single-current pathway. METHODS
      AND RESULTS: Electrodes were positioned in the right atrial appendage (RA), left
      subclavian vein (LSV), proximal coronary sinus (CSos), and distal coronary sinus
      (DCS) in 14 patients with chronic atrial fibrillation (170+/-185 days). Using a
      step-up protocol, we compared ADFTs for a single-current pathway (RA-->DCS) that
      used a single 7.5/2.5-ms biphasic shock from a 150-microF capacitor with those
      for a dual-current pathway system (RA-->DCS followed by CSos-->LSV) using
      sequential 7.5/2.5-ms biphasic shocks with capacitor discharge waveforms for 150
      microF and 600-microF capacitors. Both dual-current pathway configurations (2.0+/
      0.4 J for 150-microF capacitance, 2.4+/-0.5 J for 600-microF capacitance) had a
      significantly lower ADFT than the single-current pathway (5.1+/-1.8 J). Whereas
      the dual-current pathway with 150-microF capacitor shocks had a significantly
      lower energy threshold, there was no statistical difference in terms of leading
      edge voltage compared with the dual-current pathway with 600-microF capacitance
      shocks. There were no ventricular arrhythmias induced with appropriately
      synchronized shocks. CONCLUSIONS: For internal atrial defibrillation in humans,
      sequential biphasic waveforms delivered over dual-current pathways resulted in a
      markedly reduced (>50% reduction) ADFT compared with a single shock over a single
      current pathway.

PMID- 9657474
TI  - 31P NMR spectroscopy detects metabolic abnormalities in asymptomatic patients
      with hypertrophic cardiomyopathy.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) often causes sudden, unexpected
      death in adolescents and young adults. Alterations in myocardial metabolism are
      considered to be causes for contractile dysfunction. We examined the question of
      whether metabolic abnormalities antedate the manifestation of symptoms in
      patients with HCM. METHODS AND RESULTS: Proton-decoupled 31P NMR spectroscopy of
      the anterior left ventricular wall of the heart of 14 young, asymptomatic
      patients with HCM was performed with a 1.5-T whole-body imager. Spectra of the
      phosphate metabolites were compared with those of normal control subjects. The
      patients exhibited a significantly reduced (P<0.02) ratio of phosphocreatine
      (PCr) to ATP of 1.98+/-0.37 (mean+/-SD), compared with 2.46+/-0.53 obtained in 11
      normal control subjects. In addition, the group of patients with severe
      hypertrophy of the interventricular septum (n=8) showed a significantly increased
      (P<0.05) Pi-to-PCr ratio, with a Pi x 100/PCr of 20.0+/-8.3 versus 9.7+/-7.2 in
      control subjects. Both abnormalities are similar to those found in ischemic
      myocardium. This view is also supported by a significantly increased (P<0.01)
      phosphomonoester (PME)-to-PCr ratio, with a PME x 100/PCr of 20.7+/-11.2 compared
      with 8.4+/-6.7 in control subjects, indicating altered glucose metabolism.
      CONCLUSIONS: 31P NMR spectroscopy detects alterations of myocardial metabolism in
      asymptomatic patients with HCM. These alterations may contribute to the
      understanding of the pathophysiology and natural history of the disease.

PMID- 9657475
TI  - Assessment of QT dispersion for prediction of mortality or arrhythmic events
      after myocardial infarction: results of a prospective, long-term follow-up study.
AB  - BACKGROUND: Risk stratification by means of analysis of QT dispersion (QTD) in
      the 12-lead surface ECG is under intense investigation in various patient
      populations. The aim of the present prospective study was to evaluate the
      prognostic value of QTD and other ECG variables reflecting dispersion of
      ventricular repolarization in comparison with established risk stratifiers during
      long-term follow-up in a large cohort of post-myocardial infarction patients
      treated according to contemporary therapeutic guidelines. METHODS AND RESULTS: In
      280 consecutive infarct survivors, the 12-lead ECG was optically scanned and
      digitized for analysis of QTD (QTmax-QTmin) and 25 other repolarization
      variables, including recently developed and validated parameters such as the T
      peak-to-T end interval and the area under the T wave. In addition, a variety of
      established risk stratifiers were assessed. After a mean follow-up period of 32+/
      10 months, 30 patients reached one of the prospectively defined study end points
      (death, ventricular tachycardia, or resuscitated ventricular fibrillation).
      Comparisons between event and nonevent patients by means of Kaplan-Meier event
      probability analyses revealed that none of the ECG dispersion variables were of
      discriminative value. In contrast, variables such as left ventricular ejection
      fraction (P=0.007), mean 24-hour heart rate (P=0.022), or heart rate variability
      (P=0.007) proved to be potentially useful risk stratifiers in this patient
      population. On multivariate analysis, only LVEF, heart rate variability, and a
      history of thrombolysis were independent predictors of outcome. CONCLUSIONS:
      Determination of QTD from the surface ECG even when performed with the best
      available methodology failed to predict subsequent risk in this large series of
      infarct survivors.

PMID- 9657476
TI  - Selective ET(A) receptor antagonism reduces neointimal hyperplasia in a porcine
      coronary stent model.
AB  - BACKGROUND: As endothelin binds to ET(A) receptors, it stimulates vascular smooth
      muscle cell proliferation and may thus be pivotally involved in the pathogenesis
      of restenosis. This study assessed the ability of a potent and selective ET(A)
      antagonist to reduce neointimal hyperplasia in a porcine coronary artery stented
      injury model. METHODS AND RESULTS: Fifty-five pigs were randomized to receive
      placebo or the oral ET(A)-selective antagonist ABT147627 twice daily for 28 days
      in one of three doses: 0.75 mg/kg (low), 3.75 mg/kg (mid), and 10.0 mg/kg (high).
      Each underwent oversized stent deployment in two randomly assigned major
      epicardial coronary arteries. Three animals (5.5%) died as a consequence of stent
      thrombosis within 24 hours of the procedure. The remaining 52 animals (13 pigs
      per group) survived without complication until predetermined euthanasia at 28
      days. In the placebo group, mean injury score was 1.73+/-0.80, with a mean
      neointimal response of 0.45+/-0.24 mm. By comparison, the low-dose group had a
      similar mean injury score of 1.79+/-0.75 with reduced neointimal response, 0.36+/
      0.22 mm (P<0.01). Mean injury score in the mid-dose animals was significantly
      greater than in the placebo group (1.94+/-0.92; P<0.05). The neointimal
      hyperplasia associated with this injury was less than with placebo, although the
      difference did not reach statistical significance (0.40+/-0.25 mm; P=0.05). In
      the high-dose pigs, mean injury score was also significantly greater than in the
      placebo arm (1.93+/-0.73; P<0.05). Despite this, neointimal response was also
      significantly less (0.37+/-0.37 mm; P<0.01). CONCLUSIONS: Oral, selective ET(A)
      receptor antagonism significantly reduced neointimal hyperplasia forming over
      porcine coronary stented injuries in the first 28 days. This strategy may have
      clinical potential for the limitation and treatment of coronary restenosis after
      percutaneous revascularization.

PMID- 9657477
TI  - 99mTc-HL91: "hot spot" detection of ischemic myocardium in vivo by gamma camera
      imaging.
AB  - BACKGROUND: 99mTc-HL91 is a new hypoxia imaging agent that demonstrates increased
      uptake and retention in globally hypoxic myocardium in vitro. The purpose of this
      study was to determine whether 99mTc-HL91 could detect regional ischemia in vivo
      by gamma camera imaging. METHODS AND RESULTS: Eight open-chest dogs with left
      circumflex (LCx) stenoses were studied. Injection of 5 mCi of 99mTc-HL91 and
      microspheres was followed by imaging over 4 hours. Heart slices were imaged, then
      stained with triphenyltetrazolium chloride (TTC), and tissues were well-counted.
      TTC staining demonstrated no injury. Mean LCx blood flow was 0.32+/-0.04 mL x
      min(-1) x g(-1), and mean left anterior descending coronary artery (LAD) flow was
      0.96+/-0.02 mL x min(-1) x g(-1) (ratio, 0.33). "Hot spots" were detected in 8 of
      8 experiments in vivo within 60 minutes and improved over 4 hours. Region of
      interest analysis of LCx/LAD activity ratios demonstrated significant increases
      within 30 minutes (final ratio, 3.0; P<0.05). LCx and LAD washout curves
      demonstrated significant differences within 15 minutes. Washout curves were
      biexponential over 1 hour, followed by linear retention from 1 to 4 hours. Four
      hour fractional retention was 0.12 for LAD and 0.44 for LCx (P<0.01). Myocardial
      flow versus tracer uptake demonstrated 2 phases: phase 1 (flow, 0.05 to 0.7 mL x
      min(-1) x g(-1)) had an inverse linear correlation (r= -0.80); phase 2, (flow,
      >0.7 mL x min(-1) x g(-1)) had no correlation. Ischemic heart/liver ratios
      remained near 1.0 for 4 hours. CONCLUSIONS: 99mTc-HL91 positively identifies
      regional myocardial ischemia in a canine model using 99mTc imaging. Quantitative
      techniques allowed identification of ischemic myocardium within 15 minutes of
      tracer administration.

PMID- 9657478
TI  - Postrepolarization refractoriness versus conduction slowing caused by class I
      antiarrhythmic drugs: antiarrhythmic and proarrhythmic effects.
AB  - BACKGROUND: Conduction block may be both antiarrhythmic and proarrhythmic. Drug
      induced postrepolarization refractoriness (PRR) may prevent premature excitation
      and tachyarrhythmia induction. The effects of propafenone and procainamide on
      these parameters, and their antiarrhythmic or proarrhythmic consequences, were
      investigated. METHODS AND RESULTS: In 11 isolated Langendorff-perfused rabbit
      hearts, monophasic action potentials (MAPs) were recorded simultaneously from six
      to seven different right and left ventricular sites, along with a volume
      conducted ECG. All recordings were used to discern ventricular tachycardia (VT)
      or ventricular fibrillation (VF) induced by repetitive extrastimulation (S2-S5)
      or 10-second burst stimulation at 25 to 200 Hz at baseline and after addition of
      procainamide (20 micromol/L) or propafenone (1 micromol/L) to the perfusate. MAPs
      were analyzed for action potential duration at 90% repolarization (APD90),
      conduction times (CT) between the pacing site and the other MAPs, and PRR
      (effective refractory period-APD90=PRR) and related to the induction of VT or VF.
      During steady-state pacing, procainamide and propafenone prolonged APD90 by 12%
      and 14%, respectively. Procainamide slowed mean CT by 40% during S2-S5 pacing,
      whereas propafenone slowed mean CT by up to 400% (P<0.001 versus baseline and
      procainamide). Wavelength was not changed significantly by procainamide but was
      shortened fourfold by propafenone at S5. Both drugs produced PRR, which was
      associated with a 70% decrease in VF inducibility with procainamide and
      elimination of VF with propafenone. Despite this protection from VF, monomorphic
      VT was induced with propafenone in 57% of burst stimulations. CONCLUSIONS: Drug
      induced PRR protects against VF induction. Propafenone promotes slow monomorphic
      VT, probably by use-dependent conduction slowing and wavelength shortening.

PMID- 9657479
TI  - Images in cardiovascular medicine. Simultaneous morphological and functional
      assessment of a renal artery stent intervention with intravascular ultrasound.

PMID- 9657480
TI  - Images in cardiovascular medicine. Metabolic imaging identifies non-Hodgkin's
      lymphoma infiltrating heart.

PMID- 9657481
TI  - Diagnosing essential fatty acid deficiency.

PMID- 9657482
TI  - Predictive value of EBCT scanning.

PMID- 9657483
TI  - Testing the efficacy of lipid-lowering therapy versus revascularization: the time
      has come, or is it past due?

PMID- 9657484
TI  - Coronary calcium, subsequent events, and selection bias.

PMID- 9657485
TI  - Lipoprotein lipase gene variants and coronary risk.

PMID- 9657486
TI  - Symptomatic lumbar spinal stenosis.

PMID- 9657487
TI  - Anterior lumbosacral dislocation: case report and review of the literature.
AB  - BACKGROUND: Anterior lumbosacral dislocation is a rare traumatic anterior
      spondylolisthesis. METHODS: We report a new case surgically treated and review
      the eight cases previously reported. RESULTS: The mechanism of injury is
      hyperflexion-distraction. Neurological signs are inconsistent. Indirect
      radiological signs such as bilateral multiple transverse process fractures are
      strongly suggestive of the diagnosis. This complete soft tissue injury induces a
      definitive instability and requires an open reduction with posterior fixation.
      CONCLUSIONS: Suspicion of lumbosacral dislocation requires a computed tomography
      scan exploration with multiplanar reconstructions. Early reduction is associated
      with neurologic recovery. However, prognosis is correlated with the initial
      neurologic status and the severity of other associated injuries.

PMID- 9657488
TI  - Pain and the spine.

PMID- 9657489
TI  - Neuropsychological results of craniopharyngioma surgery in adults: a prospective
      study.
AB  - BACKGROUND: The optimal management of craniopharyngiomas is a topic of ongoing
      debate. Supporters of limited surgery for craniopharyngiomas claim that more
      radical approaches are afflicted with adverse neuropsychological sequelae. Since
      prospective studies on this issue have not yet been performed, we assessed
      neuropsychological functioning in adults before and after craniopharyngioma
      surgery. METHODS: Thirteen adults with an age range of 17-76 years (mean, 45
      years) were included in the study. Surgery included a transcranial procedure in
      10 patients. The bifrontal interhemispheric approach predominated (n = 7).
      Neuropsychological evaluation was performed before and 3 months after surgery.
      The test battery was adjusted to evaluate function related to structures in the
      operative trajectory and at the tumor site. RESULTS: A complete tumor removal was
      accomplished in eight patients and subtotal removal in three patients. IQ scores
      for verbal intelligence were in the normal range and not affected by surgery
      (mean IQ score preoperative: 106.8; postoperative 107.4). In 12 of 13 patients,
      immediate recall, delayed recall and recognition memory were not impaired after
      surgery. Postoperative results for abstract thinking were in the normal or above
      normal range. Cognitive speed was impaired in three patients preoperatively and
      in two patients postoperatively. Overall results were significantly better after
      surgery. Word fluency was not affected by surgery. Quality of life for the
      category "sleep" was impaired preoperatively, and this improved after surgery.
      Otherwise, quality of life was normal both before and after surgery. CONCLUSIONS:
      Neuropsychological performance and quality of life are generally not impaired
      after surgical removal of craniopharyngiomas. The findings support the attitude
      that the initial therapy of craniopharyngiomas should be an attempt at total
      removal.

PMID- 9657490
TI  - Large and invasive silent corticotroph-cell adenoma with elevated serum ACTH: a
      case report.
AB  - BACKGROUND: A silent corticotroph-cell adenoma (SCCA) is defined as evidence of
      immunoreactive ACTH in tumor cells of a pituitary adenoma that is not associated
      with symptoms of Cushing's disease. Most previous reports have discussed the
      etiology of this unique entity; however, the precise mechanisms of its "silence"
      are not clear yet. We discuss the pitfalls of endocrinological diagnosis and
      surgical management of SCCA. METHODS: A 63-year-old man, without the symptoms of
      Cushing's disease, demonstrated elevated serum levels of ACTH, but normal levels
      of cortisol. ACTH was measured by newly developed immunoradiometric assays (RMA),
      which are more specific for biologically active ACTH than conventional
      radioimmunoassay (RIA). The tumor was more than 3 cm in diameter and invaded both
      the cavernous sinus and the sphenoid sinus. RESULTS: Two different types of IRMAs
      revealed elevated serum ACTH levels. The tumor was removed successfully by staged
      operations. The high levels of serum ACTH were normalized after the second
      operation. CONCLUSION: The cause of the silence of SCCA is not clear yet. The
      elevated serum ACTH levels in the present case were not attributable to "Big
      ACTH." We suggest one possibility: the cause of the silence might be a minor
      variant of ACTH, detected by IRMA, leading to less biological activity of ACTH.
      This type of adenoma is invasive in nature and can potentially grow large because
      it is free of endocrinological symptoms. We emphasize the appropriate surgical
      strategy to normalize the serum levels of ACTH in case of SCCA.

PMID- 9657491
TI  - High-power diode laser in neurosurgery: clinical experience in 30 cases.
AB  - BACKGROUND: High-power semiconductor diode lasers were recently introduced and
      have been tested in ophthalmology and general surgery. These lasers are
      attractive from the practical and economical standpoint, and have enough power to
      perform most surgical procedures. They could replace other surgical lasers such
      as CO2, argon, 1.06 microm, and 1.32 microm Nd-YAG lasers for many applications
      in neurosurgery. We report our initial experience with the first available 0.805
      microm surgical diode laser, the Diomed 25 (Diomed, Ltd, Cambridge, U.K.) in a
      series of 30 patients. METHODS: The diode laser was evaluated during surgical
      resection of various types of central nervous system tumors in 30 patients. It
      was used free-hand in 27 patients in contact and non-contact, continuous wave
      (cw) and pulsed modes, and during ventricular endoscopy in three patients.
      Average time of laser use during a procedure was 248 seconds. Output power ranged
      from 1 to 25 watts, with an average power per patient of 2.64 to 15.5 watts
      (mean, 8.78 watts). Total energy delivered ranged from 65 to 11,051 joules per
      patient. RESULTS: Using 600- or 400-microm non-contact optic fiber, well
      pigmented tumor tissue hemostasis was obtained at cw 3 to 10 watts with a
      defocused beam, whereas vaporization required 10-25 cw or pulsed watts with a
      focused beam. Soft and tough tissue section could be obtained using a sculpted
      cone-shaped (600-300 microm tip) contact fiber at 7-10 cw watts after fiber tip
      charring. Because of the deeper penetration of 0.805-microm light in non
      pigmented tissues, non-contact mode is not recommended for white matter or poorly
      vascularized tumors. The contact mode was not efficient on very soft tissues such
      as edematous brain parenchyma. The contact fibers proved to be very fragile
      because of heat generation. CONCLUSIONS: The high power diode laser proved to be
      efficient for hemostasis, section and vaporization, using contact and non-contact
      modes, at different output powers. Economical and ergonomical advantages of this
      new generation of surgical lasers may cause them to replace other surgical lasers
      such as argon, CO2, and Nd-YAG lasers, mostly for tumor surgery.

PMID- 9657492
TI  - Development of a fluorescein operative microscope for use during malignant glioma
      surgery: a technical note and preliminary report.
AB  - BACKGROUND: Fluorescein has been used in the field of neurosurgery; however,
      fluorescein enhancement or contrast proved to be inadequate because of a lack of
      appropriate light sources or filters. A new operative microscope system, in which
      the microscope itself is equipped with excitation and barrier filters, and the
      application of this system to surgery for malignant glioma are reported. METHODS:
      BP 450-490, a glass interference filter used as the excitation filter for the
      light source optical system, and a Kodak Wratten No. 12 filter used as the
      barrier filter for the microscope optical system, were incorporated in the
      operative microscope. A switching apparatus was devised so that filters could be
      inserted instantly when fluorescence was to be observed. Ten cases in which the
      location of malignant glioma was enhanced by computed tomography (CT) or magnetic
      resonance imaging (MRI) were selected for this study. After incision of the dura
      mater, 8 mg/Kg body weight of fluorescein Na was injected intravenously. Tumor
      removal was begun some 20 min after the injection with the aid of this newly
      developed fluorescein operative microscope system. RESULTS: Fluorescence
      enhancement and contrast were remarkable when this system was used. It enabled
      surgical maneuvering while viewing the fluorescent image of objects. The
      boundaries between the tumor areas enhanced by CT or MRI and the surrounding
      brain could be clearly distinguished in the fluorescent image; the tumor was
      totally removed, except for deep lesions, without any neurological deterioration.
      When the tumor was relatively hard, the area surrounding the tumor was aspirated
      with a cavitron ultrasonic surgical aspirator; as a result, the tumor could be
      removed en bloc; otherwise, the fluorescent tumor was removed piece by piece.
      CONCLUSIONS: This system provides adequate fluorescent enhancement and contrast
      and is useful for observing intravenously injected fluorescein during an
      operation. Though long-term follow-up of such cases is needed, the conditions of
      our patients immediately after surgery for malignant glioma were satisfactory.
      These results suggest that our fluorescein operative microscope system is highly
      effective in surgery for malignant glioma.

PMID- 9657493
TI  - Spiral CT scanning in the detection and evaluation of aneurysms of the Circle of
      Willis.
AB  - PURPOSE: To assess the utility of spiral computed tomography (CT) with three
      dimensional reconstruction in defining aneurysms of the Circle of Willis.
      METHODS: Eighty-one patients with angiographic or surgical correlation were
      studied between 1993 and 1995, with surface rendered reconstructions of the
      arteries of the Circle of Willis. RESULTS: Spiral CT was useful in six clinical
      situations: further assessment in cases with CT suspicion of an aneurysm, follow
      up of known untreated aneurysms or aneurysm remnants, subarachnoid hemorrhage
      (SAH) with negative angiography, a past or family history of aneurysms, and
      improved definition of aneurysm anatomy. Ten of fifteen patients with previous
      surgery had no significant artifacts on the spiral study. In 66 other patients
      studied in search of aneurysms, the sensitivity of detection was 95% and
      specificity 74%. Seventeen of nineteen aneurysms 3 mm or less in size and 38 of
      39 larger were detected by spiral CT. Four of thirteen patients with SAH and
      previous negative angiography had aneurysms identified, which were confirmed at
      surgery. CONCLUSIONS: There is great promise in the use of spiral CT in
      demonstrating aneurysms of the Circle of Willis, including very small ones.
      Careful detailing of scan protocols and meticulous examination of multiplanar
      images are needed for maximum accuracy.

PMID- 9657494
TI  - Magnetic resonance angiographic source images for depicting topography and
      surgical planning for middle cerebral artery aneurysms: technique application.
AB  - PURPOSE: To evaluate the usefulness of magnetic resonance (MR) angiographic
      source images for determining the feasibility of M1 segment control via the
      distal approach in pterional craniotomy for middle cerebral artery (MCA)
      aneurysms. METHODS: MR angiographic source and conventional angiographic source
      images were obtained in 40 patients with MCA aneurysms. Each aneurysm was treated
      surgically using a pterional craniotomy. We initially approached the aneurysm
      distally. When this was judged inappropriate, the approach was altered to
      proximally. We compared the topography based on these angiograms to that
      confirmed during surgery. RESULTS: MR angiographic source images visualized the
      aneurysm, the M1 and M2 segments of the MCA, the insula, and the frontal and
      temporal opercula in all 40 patients. In 22 (55%) of them, the distal portion of
      the M1 segment was recognized from the posterolateral perspective between the
      aneurysmal neck and the insular surface. These aneurysms were successfully
      clipped via the distal approach after definite proximal control of the MCA was
      obtained. CONCLUSIONS: It was concluded that MR angiographic source images have a
      distinguishing feature in defining cerebral tissue-vascular relationships and
      that they are useful in the surgical planning for MCA aneurysms.

PMID- 9657495
TI  - Nuclear multiparameter flow cytometric DNA analysis of human brain tumors:
      correlation of DNA content with tumor histology and clinical behavior.
AB  - BACKGROUND: Using fresh surgical specimens of brain tumors to investigate
      cellular DNA content is uncommon. The aim of this study is to elucidate the
      relationship among cellular nuclear DNA content, tumor histology, and tumor
      clinical behavior of various tumors of the central nervous system. METHODS:
      Multiparameter flow cytometry (FACStar, Becton-Dickinson, San Jose, CA) was
      randomly applied to analyze 40 fresh surgical specimens from brain tumors.
      Histologically, there were 19 cases of benign tumors and 21 cases of malignant
      tumors. RESULTS: DNA distribution profiles in the benign tumors revealed 15 cases
      of diploidy and four cases of aneuploidy, while the malignant tumors had eight
      cases of diploidy and 13 cases of aneuploidy (p < 0.01). The mean DNA index (DI)
      in benign tumors was 1.13 +/- 0.27 and in malignant tumors 1.43 +/- 0.48 (p <
      0.05). The mean proliferative index (PI) in benign tumors was 10.27 +/- 5.46% and
      18.44 +/- 8.98% in malignant tumors (p < 0.05). Clinically, 10 patients had
      postoperative recurrence. The PI in recurrent and nonrecurrent tumors was 17.83
      +/- 11.13% and 13.20 +/- 7.19%, respectively (p < 0.05). The 1-year cumulative
      survival rate in benign tumors was 78.9%, and 57.1% in malignant tumors (p <
      0.05). CONCLUSIONS: Malignant tumors had a significantly higher incidence of
      aneuploid DNA histograms, a higher DNA index, and a higher proliferative index.
      Tumors with a high PI had a higher incidence of recurrence and a lower survival
      rate. Multiparameter DNA analysis by flow cytometry provides a valuable
      diagnostic aid for the histopathologic differentiation of human brain tumors.

PMID- 9657496
TI  - Surgical treatment of benign intracranial hypertension--subtemporal decompression
      revisited.
AB  - BACKGROUND: Subtemporal decompression, first advocated by Dandy for the treatment
      of benign intracranial hypertension or pseudotumor cerebri, has been replaced as
      a treatment mainstay by medical management using diuretics, steroids, and lumbar
      puncture. Failure of these forms of treatment has frequently led to insertion of
      cerebrospinal fluid shunts. METHODS: We have retrospectively reviewed the long
      term outcome of eight patients who were treated by subtemporal decompression
      (STD) for classical presentations of refractory benign intracranial hypertension.
      The follow-up period ranged from 8 to 26 years. RESULTS: Within 1 month of STD,
      deterioration in visual fields and acuity resolved in all eight patients. Five of
      eight patients required CSF diversion procedures after subtemporal decompression
      to control headaches. No patient experienced recurrent permanent visual
      deterioration after STD. CONCLUSION: STD may be the most effective treatment in
      both long and short term follow-up to provide lasting relief and prevention of
      visual morbidity caused by refractory benign intracranial hypertension.

PMID- 9657497
TI  - Continuous external CSF drainage--a perpetual problem in neurosurgery.
AB  - BACKGROUND: Continuous external CSF drainage represents a well established
      procedure which has been improved by many technical contributions. We present our
      experience in a prospective study of 212 needle trephinations in 165 consecutive
      patients with a new screw fixation device. METHODS: The entire procedure is
      performed at the bedside under local anesthesia with a twist drill. The
      trephination needle is inserted into the self-tapping cannulated screw fixed to
      the skull. RESULTS: The mean operation time was 6 min, and the duration of
      ventricular drainage ranged from 2 h to 44 days. Ninety-one percent (N = 193) of
      ventricular needles in our series were placed at the first targeting attempt. ICP
      monitoring and -therapy (88%) were the main indications for needle trephination
      in our study. During the study period we observed needle associated
      complications, such as intracerebral hemorrhages (N = 2, 1%) and infections (N =
      17, 8%). CONCLUSIONS: Concerning infection, primary insufficient fixation, and
      general surgical handling, we found a clear learning curve during the course of
      our study. In spite of the initial problems at the time of introduction we have
      to emphasize the outstanding advantages of the new ventriculostomy device: It is
      a time-saving bedside procedure equipped with an optimum fixation device and it
      enables uncomplicated exchange of the needle in case of obstruction.

PMID- 9657498
TI  - Neurosurgery of the peripheral nervous system: cubital tunnel syndrome.

PMID- 9657499
TI  - Differentiating external hydrocephalus from chronic subdural hematoma.

PMID- 9657500
TI  - Advice to young neurosurgeons.

PMID- 9657501
TI  - What kind of business is medicine--from a business perspective?

PMID- 9657502
TI  - Strategic planning for neurosurgeons.

PMID- 9657503
TI  - Tuberculosis: where do we stand?

PMID- 9657504
TI  - An investigation into the interaction between drug efficacy and drug price of
      praziquantel in determining the cost-effectiveness of school-targeted treatment
      for Schistosoma mansoni using a population dynamic model.
AB  - A population dynamic model of schistosome transmission was used to investigate
      the interaction between drug efficacy and drug price of different brands of
      praziquantel in determining the cost-effectiveness of school-targeted treatment
      for Schistosoma mansoni. In this analysis, costs were affected by coverage, drug
      price and distance travelled, and effectiveness by coverage and drug efficacy.
      Four effectiveness measures were assessed: the number of infection case-years
      prevented, heavy infection case-years prevented, hepatomegaly case-years
      prevented and fibrosis case-years prevented. The interactions between drug
      efficacy and drug price were complex. In particular, there was a highly nonlinear
      relationship between drug efficacy and cost-effectiveness, with drugs of low
      efficacy producing high and variable cost-effectiveness ratios, particularly when
      other programme costs related to distance travelled were high. The results
      suggest that given the current price range of praziquantel, a drug with less than
      a 50% chance of killing the worms is not to be recommended. This has important
      practical implications for the widespread use of praziquantel, since most
      international agencies procure praziquantel purely on the basis of price. There
      is clearly a need for studies which evaluate the efficacy of new brands of
      praziquantel, and more credence should be given to the use of high efficacy
      brands, not only in terms of maximizing the cost-effectiveness of the
      intervention programme, but also in delaying the onset of drug resistance.

PMID- 9657505
TI  - Verbal autopsies for adult deaths: their development and validation in a
      multicentre study.
AB  - BACKGROUND: Verbal autopsy (VA) has been widely used to ascertain causes of child
      deaths, but little is known about the usefulness of VA for adult deaths. This
      paper describes the process used to develop a VA tool for adult deaths and the
      results of a multicentre validation of this tool. METHODS: A mortality
      classification was developed by including causes of death that might be arrived
      at by VAs and causes that are responsive to public health interventions. An
      algorithm was designed for each cause in the classification, based on classifying
      symptoms into essential, supportive and differential. A structured questionnaire
      designed to elicit information on these symptoms was developed in English
      translated into the local languages. The tool was validated on deaths occurring
      at hospitals in Tanzania (315 deaths), Ethiopia (249) and Ghana (232). Hospital
      records of all adult deaths occurring at the study hospitals from June 1993 to
      April 1995 were collected prospectively. Non-medical interviewers with at least
      12 years of formal education conducted VA interviews. Causes of death were
      diagnosed by a panel of physicians and by a computerized algorithm. The validity
      of the VA was assessed by comparing the VA diagnoses with hospital diagnoses.
      RESULTS: Specificity of VAs by physicians fell below 95% only for acute febrile
      illness (AFI) and TB/AIDS. Sensitivity and positive predictive value (PPV),
      however, varied widely both across the sites and between causes. Sensitivity was
      > 75% for tetanus, rabies, direct maternal causes, injuries and TB/AIDS and
      ranged between 60% and 74% for diarrhoea, acute abdominal conditions and AFI. The
      PPV was > 75% for tetanus, rabies, hepatitis and injuries and ranged between 60
      and 74% for meningitis, AFI, TB/AIDS and direct maternal causes. When the
      communicable diseases were combined in a single group, the sensitivity was 82%,
      specificity 78% and PPV 85%. For the group of noncommunicable diseases the
      corresponding sensitivity, specificity and PPV were 71%, 87% and 67%,
      respectively. Use of an algorithm resulted in lower sensitivity, specificity and
      PPV than the VAs by physician. CONCLUSION: VAs by a panel of physicians performed
      better than an opinion-based algorithm. The validity of VA diagnosis was highest
      for AFI, direct maternal causes, TB/AIDS, tetanus, rabies and injuries.

PMID- 9657506
TI  - Maternal anthropometry-based screening and pregnancy outcome: a decision
      analysis.
AB  - OBJECTIVE: To assess the impact of screening and intervention based on maternal
      height, prepregnancy weight and weight during weeks 16-19 or 24-27 in reducing
      adverse pregnancy outcomes (IUGR, preterm birth and assisted delivery) in
      developing country settings. METHODS: Decision analysis based on a recent
      multicentre WHO collaborative study of maternal anthropometry and pregnancy
      outcomes and meta-analyses of controlled clinical trials of balanced
      energy/protein supplementation (for IUGR and preterm birth) and support from
      caregivers during labour (for assisted delivery). Subjects for the analysis
      comprised pregnant women from Cali, Colombia (1989, n = 4598); urban and rural
      Pune, India (1990, n = 4307); and urban and rural Myanmar (1981-82, n = 3542)
      followed until delivery. RESULTS: Seven to 45% of pregnant women had positive
      screens, with preventive fractions (PFs) ranging from 0.034 to 0.109 for IUGR,
      0.027-0.082 for preterm birth and 0.011-0.105 for assisted delivery. Screening
      prevention ratios (SPRs = ratios of the number of women treated to the number of
      cases of adverse outcome prevented) are high in all three study settings for
      preterm birth and assisted delivery (range 22.8-115.7) and low in settings with a
      high prevalence of the adverse outcome and high specificity of the anthropometric
      measure (India for IUGR, range 7.0-8.0). Sensitivity analyses demonstrate a
      marked linear fall in PF and an exponential rise in the SPR as the relative risk
      associated with intervention increases (i.e. as the protective benefit of
      intervention decreases) from 0.60 to 0.95. CONCLUSIONS: A maternal anthropometry
      based 'risk approach' is unlikely to result in a major reduction in adverse
      pregnancy outcomes in developing country settings. For risk-free and inexpensive
      interventions (e.g. caregiver support during labour), a better strategy would be
      to forego screening and instead treat all pregnant women.

PMID- 9657507
TI  - Financing changes of schistosomiasis control programmes in China 1980-1995: a
      case study in Songzi county.
AB  - To assess the financing changes of schistosomiasis control programmes in China
      and estimate the impact of these changes on patients' treatment-seeking behaviour
      and control of schistosomiasis, a survey was conducted in five schistosomiasis
      endemic areas of the lake regions, Hubei province, in 1996. This paper reports
      financing changes and their impact on the incidence and prevalence of
      schistosomiasis from one of the five areas as a case study. By examining the
      surveillance and financial data from 1980 to 1995, and through focus group
      discussions we found that the schistosomiasis control programmes in People's
      Republic of China have gone through dramatic financing changes from 1980 to 1995,
      when the transitions of China's social, economic, and political systems happened.
      The proportions of funding to schistosomiasis control programmes from high level
      governmental agencies, county budgets, and services revenue changed from 60%,
      23%, and 17%, respectively, in 1980-1987 to 0.7%, 22.3%, and 72% in 1995. The
      percentages of expenditure of schistosomiasis control activities, salaries and
      bonuses, and other activities unrelated to schistosomiasis control, were 53.5%,
      14.4, and 17.2% in 1980. These percentages changed to 7.7%, 33.3%, and 53.3%,
      respectively, in 1995. The preponderant role of the state in organizing,
      financing, and delivery of the services was replaced with the new system which is
      more influenced by the market economy. The incidence and the prevalence of
      schistosomiasis in the study area have increased year by year from 1980 to 1990,
      although there has been a tendency to decrease after 1991 but not to the low
      pre1980 levels. The collapse of the community-based medical system in rural areas
      and the dramatic financing changes of schistosomiasis control programmes have
      created major difficulties for schistosomiasis control in China.

PMID- 9657508
TI  - Albendazole plus praziquantel versus albendazole alone as a pre-operative
      treatment in intra-abdominal hydatisosis caused by Echinococcus granulosus.
AB  - OBJECTIVE: To compare the effects of a combined medication of albendazole (10
      mg/kg/day) plus praziquantel (25 mg/kg/day) to those of albendazole alone at
      different doses (10 and 20 mg/kg/day). METHOD: The protoscoleces' viability was
      studied in a consecutive series of patients affected by intra-abdominal
      hydatidosis caused by Echinococcus granulosus. In all cases the drugs were given
      during the month prior to surgery. RESULTS: A significant increase of patients
      with nonviable protoscoleces was observed in the group treated with the
      scolicides combination compared to those treated with albendazole alone, both at
      a dose of 10 mg/kg/day (P = 0.004) and at a dose of 20 mg/kg/day (P = 0.03).
      Albendazole sulphoxide levels in serum and in cyst fluid were higher in patients
      given the combined therapy than in those who received only albendazole (10
      mg/kg/day: P = 0.016; 20 mg/kg/day: P = 0.034). Levels in the cysts were not
      significantly different probably due to the sample size; nevertheless a lineal
      relation between the values obtained in serum and inside the cysts could be
      discerned in the patients treated with the combined medication. CONCLUSION:
      Albendazole plus praziquantel is more effective than monotherapy with albendazole
      in the preoperative treatment of intra-abdominal hydatidosis.

PMID- 9657509
TI  - Filarial elephantiasis among Haitian women: social context and behavioural
      factors in treatment.
AB  - Few studies have addressed the social and behavioural aspects of lymphatic
      filariasis. The research reported here investigated the ethnographic context of
      filarial elephantiasis among women in Leogane, Haiti, and focused on explanatory
      models of the illness, the impact of the disease on women's lives, and the
      difficulties patients experienced in following a therapeutic regimen provided at
      a local hospital. Qualitative data were collected through focus group and
      individual interviews and direct observation of patients enrolled in the
      treatment programme. Results indicate that traditional understanding and
      treatment for the disease are prevalent in the community, although biomedical
      explanations are gaining credence as a consequence of long-term filariasis
      control activities in this area. Women's lives are substantially burdened both
      socially and economically by the physical impairment of elephantiasis, most
      notably in the loss of income due to restrictions on mobility. The degree of
      social discrimination encountered varies by the timing of onset of symptoms in
      the life course. Difficulties encountered with the physical therapy regimen
      included maintenance of the compressive bandage and availability of suitable foot
      wear. Similarities between these findings and those reported for other parts of
      the world are noted. Recommendations from the study cite the need for community
      education and peer support activities to provide a knowledge base and support
      structure for current and future intervention programmes.

PMID- 9657510
TI  - Key indicators for the monitoring and evaluation of control programmes of human
      African trypanosomiasis due to Trypanosoma brucei gambiense.
AB  - Very little research has been devoted to the design of epidemiological tools for
      the monitoring and evaluation of National Human African Trypanosomiasis (HAT)
      Control Programmes and daily management decisions are made in the absence of
      accurate knowledge of the situation. This paper identifies key indicators
      necessary to make decisions in the field and constantly adjust control activities
      to changing situations. Examples are derived from the Medecins Sans Frontieres
      (MSF) HAT Control Programme in Adjumani, Uganda. Based on the principles of
      quality assurance, the focus is placed on process indicators. A conceptual
      framework derived from a system view/planning cycle perspective is also described
      for the construction of indicators. Finally, some specific challenging aspects of
      the epidemiology of HAT are presented and the limitations of the interpretation
      of the indicators discussed.

PMID- 9657511
TI  - Quinine pharmacokinetics: ototoxic and cardiotoxic effects in healthy Caucasian
      subjects and in patients with falciparum malaria.
AB  - OBJECTIVE: To study the pharmacokinetic behaviour of quinine in Caucasians with
      and without malaria. METHOD: Quinine-dihydrochloride was administered
      intravenously as a single dose of 300 mg to 12 healthy subjects and as multiple
      doses of 600 mg in 4 h every 8 h in 10 patients with falciparum malaria. Plasma
      quinine concentrations were measured by high-performance liquid chromatography
      RESULTS: Quinine pharmacokinetics are time-dependent: the apparent elimination
      halftime is shorter in the accumulation phase than in the elimination phase; in
      malaria patients the maximal quinine concentration was reached in half the time
      calculated on the basis of the elimination phase after the last quinine infusion.
      Nevertheless a loading dose seemed advisable to reach adequate therapeutic levels
      quickly. In malaria patients the highest plasma concentrations during or at the
      end of the infusions were positively correlated with body weight. There was no
      correlation between body weight and the volume of distribution of quinine as
      calculated during the elimination phase. Hearing loss was audiometrically
      documented in 9 healthy subjects at a mean maximal plasma quinine concentration
      of only 2 mg/l. All malaria patients suffered serious cochlear hearing
      impairment. The ototoxic effects in both healthy subjects and patients appeared
      to be reversible. No electrographic changes were noted in the healthy subjects,
      whereas a clinically insignificant mean lengthening of the corrected QT interval
      was seen in the malaria patients. CONCLUSION: Intravenous quinine
      pharmacokinetics in healthy Caucasians were similar to those reported for
      Nigerian or Thai subjects. At effective doses quinine causes considerable but
      reversible cochlear hearing losses in both healthy persons and in patients. Our
      findings do support the need for a loading dose. The fact that in malaria
      patients there was no correlation between body weight and quinine VD as
      calculated during the elimination phase renders questionable the usefulness of
      dosing quinine according to body weight.

PMID- 9657512
TI  - Distinction of recrudescences from new infections by PCR-RFLP analysis in a
      comparative trial of CGP 56 697 and chloroquine in Tanzanian children.
AB  - OBJECTIVE: To test the efficacy of a new compound drug (CGP 56697) against acute,
      uncomplicated falciparum malaria. METHOD: Reappearing parasites were analysed by
      PCR-RFLP within a randomized controlled trial. 130 patients received chloroquine
      and 130 patients were treated with CGP 56697. Samples from 96 patients with
      parasitological failure were tested by PCR-RFLP for MSP2 of Plasmodium
      falciparum. Seven days after treatment 32 patients of the chloroquine control
      group with reappearing parasites were tested by PCR and one infection was
      unequivocally determined as a new infection. After 7 days, in the CGP 56697
      group, 6 samples were tested in which one new infection was identified. Similar
      observations were made one and three weeks later in both groups. RESULTS:
      Although a high multiplicity of infections on admission was observed, there was
      no significant correlation between multiplicity and either recrudescence or new
      infection. Patients in both treatment groups with subsequent recrudescent
      parasites had higher initial mean parasite densities than patients who cleared.
      Those of the patients with recrudescent parasites who were treated with CGP 56697
      had higher initial parasite densities than those treated with chloroquine. The
      rate of re-infection increased with time as expected in holoendemic areas and
      appeared to be higher in chloroquine patients. Generally, CGP 56697 showed a
      superior clearance rate, successfully cleared higher parasite densities and
      suppressed new infections over a longer period of time. CONCLUSION: The PCR
      analysis confirmed that reinfections beyond day 7 are significant in areas highly
      endemic for malaria and showed the necessity of excluding these when estimating
      14 day clearance rates. Provided new infections are excluded, the 28-day
      clearance rate can also be used to determine the efficacy of antimalarial drugs
      in highly endemic areas, and adds to our knowledge of drug resistance and
      dynamics of infections in people living in such areas.

PMID- 9657513
TI  - Efficacy and safety of CGP 56697 (artemether and benflumetol) compared with
      chloroquine to treat acute falciparum malaria in Tanzanian children aged 1-5
      years.
AB  - A randomized, open trial involving 260 Tanzanian children, aged 1-5 years, with
      acute Plasmodium falciparum malaria was conducted to evaluate the efficacy of the
      combination antimalarial CGP 56697 (artemether and benflumetol), and to compare
      it with chloroquine, the standard drug used for malaria treatment in the
      Kilombero area. Children who had received rescue medication within the first 48 h
      or had a negative slide at the same time were excluded. Seven-day parasitological
      cure rates were 94% (95% CI 88-97.5) for CGP 56697 and 35.4% (95% CI 25.9-45.8)
      for chloroquine. Using the same definition, the 14-day parasitological cure rates
      were 86.4% (95% CI 78.5-92.2) for CGP 56697 and 10.3% (95% CI 5.1-18.1) for
      chloroquine. Gametocytes were more effectively suppressed by CGP 56697 than by
      chloroquine. There were no major adverse events with either drug. CGP 56697 is
      highly efficacious against P. falciparum in this area of Tanzania. The study
      contributes to the discussion on treatment strategies, particularly whether
      chloroquine may still fulfil its role as first-line drug in an area of high
      malaria transmission and very high levels of chloroquine resistance.

PMID- 9657514
TI  - Human occult loiasis: field evaluation of a nested polymerase chain reaction
      assay for the detection of occult infection.
AB  - A nested polymerase chain reaction (nested PCR) assay, targeted on the repeat 3
      region (15r3) of the gene coding for a Loa loa 15 kD polyprotein, was developed
      to detect L. loa infection. The assay has a sensitivity of 95% and is 100%
      specific with regard to sympatric filarial parasites: Mansonella perstans,
      Onchocerca volvulus and Wuchereria bancrofti. In this field study in a mixed
      filarial (L. loa and M. perstans) endemic region of Gabon, 157 L. loa
      amicrofilaraemic blood samples (AMF; diagnosed by leucoconcentration followed by
      standard microscopic examination) from the residents from four villages were
      screened by the 15r3-nested PCR assay. The assay detected 106 occult infected
      subjects among the 157 AMF individuals (68%), including 59 of 87 adults (68%) and
      47 of 70 children (67%). In each village the prevalence of occult infection was,
      respectively, 38%, 52%, 79% and 80% for Moyabi, Djoutou, N'djokaye and Okoumbi.
      The annual transmission potential (ATP) of loiasis has been estimated to be 250
      infective larvae (L 3) per man per year for Moyabi and Djoutou, 1800 for
      N'djokaye and 433000 L3/man/year for Okoumbi. This implies a correlation between
      occult infection of loiasis and the intensity of transmission. By contrast, the
      prevalence of L. loa microfilariae was 21% for Okoumbi, 22%, for N'djokaye and
      19% for Djoutou and Moyabi. These results show that the prevalence of loiasis in
      this region of Gabon is higher than previously described by standard microscopic
      examination and that the application of this assay will be significant in the
      development of control strategies for loiasis.

PMID- 9657515
TI  - Towards new partnerships for health development in developing countries: the
      contractual approach as a policy tool.
AB  - What roles for government but also for society's groups in the advancement of
      public health in developing countries? This paper focuses on the need to adopt
      the contractual approach as a powerful policy tool and sketches the contours of a
      policy framework for good contracting. A short historical review of health system
      changes leads up to a discussion of the current emergence of a multitude of
      actors, the forging of alliances between the various partners, examples on how
      significant health policy benefits might be secured through contracting, and the
      implications of building alliances, such as defining and assigning accountability
      to the contracting partners.

PMID- 9657516
TI  - A bill of responsibilities for whistleblowers in science.

PMID- 9657517
TI  - A new look at thin filament regulation in vertebrate skeletal muscle.
AB  - It is 30 years since Ebashi and colleagues showed that Ca2+ ions directly affect
      regulation of the myosin-actin interaction in muscle through the action of
      tropomyosin and troponin on muscle thin filaments. It is more than 20 years since
      the idea was put forward that tropomyosin might act, at least in part, by
      changing its position on actin, thus uncovering or modifying the myosin binding
      site on actin when troponin molecules take up Ca2+. Since that time, a great deal
      of evidence for and against this steric blocking mechanism has been published: a
      structure for actin filaments at close to atomic resolution has been proposed,
      and the whole regulation story has become both more complicated and more subtle.
      Here we review structural and biochemical aspects of regulation in vertebrate
      skeletal muscle. We show that some basic ideas of the steric blocking mechanism
      remain valid. We also show that additional factors, such as troponin movements
      and structural changes within the actin monomers themselves, may be crucial. A
      number of the resulting regulation scenarios need to be distinguished.

PMID- 9657518
TI  - Expressional control of the 'constitutive' isoforms of nitric oxide synthase (NOS
      I and NOS III).
AB  - Nitric oxide synthase (NOS) exists in three established isoforms. NOS I (NOS1,
      ncNOS) was originally discovered in neurons. This enzyme and splice variants
      thereof have since been found in many other cells and tissues. NOS II (NOS2,
      iNOS) was first identified in murine macrophages, but can also be induced in many
      other cell types. NOS III (NOS3, ecNOS) is expressed mainly in endothelial cells.
      Whereas NOS II is a transcriptionally regulated enzyme, NOS I and NOS III are
      considered constitutively expressed proteins. However, evidence generated in
      recent years indicates that these two isoforms are also subject to expressional
      regulation. In view of the important biological functions of these isoforms,
      changes in their expression may have physiological and pathophysiological
      consequences. This review recapitulates compounds and conditions that modulate
      the expression of NOS I and NOS III, summarizes transcriptional and
      posttranscriptional effects that underlie these changes, and-where known
      describes the molecular mechanisms leading to changes in transcription, RNA
      stability, or translation of these enzymes.

PMID- 9657519
TI  - Proteins that specifically recognize cisplatin-damaged DNA: a clue to anticancer
      activity of cisplatin.
AB  - Cisplatin, but not its trans geometric isomer, is a potent anticancer drug whose
      biological activity is a consequence of the formation of covalent adducts between
      the platinum compound and certain bases in DNA. Two classes of proteins have
      recently been identified that bind preferentially to damaged sites: proteins that
      specifically recognize those sites as a first step in their repair, and those
      that bind to such sites by virtue of structural similarity between the modified
      DNA and their own natural binding sites. Both classes of proteins may be
      involved, perhaps in opposing ways, in the cytotoxic effect of the drug.

PMID- 9657520
TI  - Antisense telomerase treatment: induction of two distinct pathways, apoptosis and
      differentiation.
AB  - Telomerase, the enzyme that elongates telomeric DNA (TTAGGG)n, may be involved in
      cellular immortality and oncogenesis. To investigate the effect of inhibition of
      telomerase on tumor cells, we transfected the antisense vector against the human
      telomerase RNA into human malignant glioma cells exhibiting telomerase activity.
      After 30 doublings, some subpopulations of transfectants expressed a high level
      of interleukin-1beta-converting enzyme (ICE) protein and underwent apoptosis. In
      contrast, other subpopulations also showed enhanced ICE protein but escaped from
      apoptotic crisis and continued to grow, although their DNA synthesis, invasive
      ability, and tumorigenicity in nude mice were significantly reduced. Surviving
      cells demonstrated increased expression of glial fibrillary acidic protein and
      decreased motility, consistent with a more differentiated state. These cells also
      contained enhanced expression of the cyclin-dependent kinase inhibitors (CDKIs)
      p21 and p27. Treatment of surviving nonapoptotic cells with antisense
      oligonucleotides against p27, but not p21, induced apoptotic cell death,
      suggesting that p27 may have protected differentiating glioma cells from
      apoptosis. These data show that treatment with antisense telomerase inhibits
      telomerase activity and subsequently induces either apoptosis or differentiation.
      Regulation of these two distinct pathways may be dependent on the expression of
      ICE or CDKIs.

PMID- 9657522
TI  - Oxidized LDL promotes vascular endothelial cell pinocytosis via a prooxidation
      mechanism.
AB  - Human low density lipoprotein (LDL) is prepared in the presence of antioxidants
      and is oxidized to different levels (measured by thiobarbituric acid reactive
      substance) with copper ion. The effects of unoxidized LDL and oxidized LDL (ox
      LDL) on stress fiber formation, cell membrane ruffling, and pinocytosis (measured
      by [14C]sucrose uptake) in cultured human umbilical cord vein endothelial cells
      (EC) are compared. We show that at a concentration range of 100 to 200 microg
      cholesterol/ml, both unoxidized LDL and ox-LDL promote EC elongation and stress
      fiber formation, but the effect by the latter is more prominent when compared at
      the same dose range. In addition, ox-LDL also induces EC membrane ruffling and
      promotes pinocytosis. These effects are positively correlated with the extent of
      LDL oxidation and depend on the dose of ox-LDL. Ox-LDL-promoted membrane ruffling
      and pinocytosis are effectively blocked by brief preexposure of the cells to
      antioxidants. In contrast, stress fiber formation is not affected by antioxidant
      pretreatment. Although unoxidized LDL also promotes [14C]sucrose uptake, it is
      less potent than ox-LDL and significantly higher concentrations are required to
      produce a detectable effect. Unlike ox-LDL, unoxidized LDL-enhanced pinocytosis
      is not accompanied by the appearance of membrane ruffling; therefore, they may
      act via different mechanisms. Elevated pinocytosis may increase transcytotic
      activity of the endothelium, leading to an increased influx of plasma components
      such as LDL into the subendothelial space.

PMID- 9657521
TI  - The unimportance of being (protein kinase C) epsilon.
AB  - The purpose of our study was to determine the mechanism through which phorbol
      esters and smooth muscle myosin phosphatase inhibitors can induce contraction of
      smooth muscle in the absence of Ca2+. Protein kinase C-epsilon (PKC-epsilon) was
      previously implicated in this process based largely on its supposed absence in
      the ferret portal vein, and a correlation was drawn between the presence of this
      isoform and the ability of smooth muscle to contract independently of Ca2+ and
      phosphorylation of the 20 kDa regulatory light chains of myosin (MLC20). We
      demonstrate here, with two antibodies, one to the NH2 terminus and the other to
      the COOH terminus of PKC-epsilon, that epsilon is present in both ferret portal
      vein and rabbit portal vein smooth muscle, neither of which exhibits phorbol
      ester-induced contraction in the absence of Ca2+. However, in the presence of
      clamped submaximal Ca2+, phorbol es ter increased MLC20 phosphorylation from
      17.7+/-1.7% to 46.4+/-3.6% in ferret portal vein smooth muscle and evoked an
      increase in force. Prolonged (48 h) incubation of ferret portal vein with phorbol
      esters completely down-regulated PKC-epsilon, as shown by Western blots, and
      abolished the phorbol ester-evoked contraction at submaximal Ca2+, but not Ca2+
      independent, contractions induced by the phosphatase inhibitor microcystin.
      Contractions induced by microcystin in Ca2+-free solution were associated with
      increased phosphorylation of myosin light chain kinase (MLCK). Activation of MLCK
      by autophosphorylation in the absence of Ca2+ occurs in vitro (1). We conclude
      that PKC-epsilon is neither necessary nor sufficient for Ca2+-independent
      regulation of myosin II in smooth muscle, but contractions induced by agents that
      inhibit smooth muscle myosin phosphatase in the absence of Ca2+ may be mediated
      by MLCK autophosphorylated or activated by another Ca2+-independent kinase.

PMID- 9657523
TI  - Localization, quantification, and activation of platelet-activating factor
      receptor in human endometrium during the menstrual cycle: PAF stimulates NO,
      VEGF, and FAKpp125.
AB  - Implantation is characterized by an inflammatory-like response with expansion of
      extracellular fluid volume, increased vascular permeability, and vasodilatation.
      These effects are believed to be mediated at the paracrine level by prostaglandin
      E2 and platelet-activating factor (PAF), but the cellular mechanism (or
      mechanisms) remains largely unknown. We demonstrate that PAF receptor (PAF-R)
      immunoreactivity and mRNA are detected in proliferative and secretory endometrial
      glands, however, the responsiveness of endometrium to physiological
      concentrations of PAF is confined predominantly to the secretory endometrium.
      Semiquantitative reverse transcription-polymerase chain reaction revealed that
      PAF-R transcript levels were highest in the mid-late proliferative and late
      secretory phases of the cycle. Interaction of PAF with its receptor resulted in
      the rapid release of nitric oxide (NO), increased expression of vascular
      endothelial growth factor (VEGF), and activation of FAKpp125, a focal adhesion
      kinase, demonstrating that the PAF-R is functionally active. Inhibition of NO
      synthesis by NG-monomethyl-L-arginine produced dose-dependent attenuation of PAF
      evoked NO release, indicating NOS activation; the dependency of PAF-evoked NO
      release on PKC and extracellular Ca2+ was confirmed by PKC inhibitor Ro 31-8220
      and by the removal of extracellular Ca2+. PAF up-regulated VEGF gene expression
      in a concentration- and time-dependent fashion in human endometrial epithelial
      cell lysates. Transcription of VEGF was rapidly followed by secretion of the
      protein. These data support our premise that this autocoid acts as an angiogenic
      mediator in the regeneration of the endometrium after menses and as a vasodilator
      to promote blastocyst attachment during the implantation process.

PMID- 9657524
TI  - TR1, a new member of the tumor necrosis factor receptor superfamily, induces
      fibroblast proliferation and inhibits osteoclastogenesis and bone resorption.
AB  - A newly identified member of the tumor necrosis factor receptor (TNFR)
      superfamily shows activities associated with osteoclastogenesis inhibition and
      fibroblast proliferation. This new member, called TR1, was identified from a
      search of an expressed sequence tag database, and encodes 401 amino acids with a
      21-residue signal sequence. Unlike other members of TNFR, TR1 does not contain a
      transmembrane domain and is secreted as a 62 kDa glycoprotein. TR1 gene maps to
      chromosome 8q23-24.1 and its mRNA is abundantly expressed on primary osteoblasts,
      osteogenic sarcoma cell lines, and primary fibroblasts. The receptors for TR1
      were detected on a monocytic cell line (THP-1) and in human fibroblasts.
      Scatchard analyses indicated two classes of high and medium-high affinity
      receptors with a kD of approximately 45 and 320 pM, respectively. Recombinant TR1
      induced proliferation of human foreskin fibroblasts and potentiated TNF-induced
      proliferation in these cells. In a coculture system of osteoblasts and bone
      marrow cells, recombinant TR1 completely inhibited the differentiation of
      osteoclast-like multinucleated cell formation in the presence of several bone
      resorbing factors. TR1 also strongly inhibited bone-resorbing function on dentine
      slices by mature osteoclasts and decreased 45Ca release in fetal long-bone organ
      cultures. Anti-TR1 monoclonal antibody promoted the formation of osteoclasts in
      mouse marrow culture assays. These results indicate that TR1 has broad biological
      activities in fibroblast growth and in osteoclast differentiation and its
      functions.

PMID- 9657525
TI  - Protein kinase A type I antagonist restores immune responses of T cells from HIV
      infected patients.
AB  - Cyclic AMP-dependent protein kinase A (PKA) type I has been established as an
      acute inhibitor of T cell activation. For this reason, we investigated the
      possible role of PKA type I in HIV-induced T cell dysfunction. T cells from HIV
      infected patients have increased levels of cAMP and are more sensitive to
      inhibition by cAMP analog than are normal T cells. A PKA type I-selective
      antagonist increases the impaired proliferation of T cells from HIV-infected
      patients to normal or subnormal levels (up to 2.8-fold). Follow-up of patients
      after initiation of highly active antiretroviral treatment revealed that a
      majority of patients have a persistent T cell dysfunction that is normalized by
      incubation of T cells with Rp-8-Br-cAMPS. These observations imply that increased
      activation of PKA type I may contribute to the progressive T cell dysfunction in
      HIV infection and that PKA type I may be a potential target for immunomodulating
      therapy.

PMID- 9657526
TI  - Redox priming of the insulin receptor beta-chain associated with altered tyrosine
      kinase activity and insulin responsiveness in the absence of tyrosine
      autophosphorylation.
AB  - Induction of tyrosine kinase activity of the insulin receptor (IR) beta-chain is
      believed to require its autophosphorylation at Tyr1162, Tyr1163, and Tyr1158.
      However, the mechanism of the initial phosphorylation is poorly understood. We
      show that treatment of IR-transfected Chinese hamster ovary cells with
      antioxidants inhibits insulin responsiveness. Conversely, partial inhibition of
      glutathione biosynthesis by buthionine sulfoximine (BSO) and glutathione
      reductase by 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU), i.e., procedures that
      intracellularly induce mildly oxidative conditions, caused a decrease in IR beta
      chain sulfhydryl groups and enhanced synergistically the induction of IR tyrosine
      phosphorylation by insulin. The IR beta-chain from cells treated with BSO/BCNU in
      the absence of insulin was not detectably tyrosine phosphorylated, but
      nevertheless was functionally altered, as demonstrated in vitro by a moderate
      kinase activity at lowATP concentrations (5 nM) and a strong kinase activity at
      25 microM ATP. This activity was found to be specific for tyrosine (not for
      serine or threonine), and tryptic peptide maps indicated that it is more
      selective than that induced by insulin. Moreover, the kinase activity from
      BSO/BCNU-treated cells showed a spontaneous decay that was not prevented by the
      phosphatase inhibitor vanadate. Together, these results suggest that optimal
      insulin responsiveness may require a process of 'redox priming' of the IR beta
      chain that involves structural and functional changes in the absence of
      detectable tyrosine phosphorylation of the beta-chain.

PMID- 9657527
TI  - Skeletal muscle myocytes undergo protein loss and reactive oxygen-mediated NF
      kappaB activation in response to tumor necrosis factor alpha.
AB  - Skeletal muscle atrophy and weakness are thought to be stimulated by tumor
      necrosis factor alpha (TNF-alpha) in a variety of chronic diseases. However,
      little is known about the direct effects of TNF-alpha on differentiated skeletal
      muscle cells or the signaling mechanisms involved. We have tested the effects of
      TNF-alpha on the mouse-derived C2C12 muscle cell line and on primary cultures
      from rat skeletal muscle. TNF-alpha treatment of differentiated myotubes
      stimulated time- and concentration-dependent reductions in total protein content
      and loss of adult myosin heavy chain (MHCf) content; these changes were evident
      at low TNF-alpha concentrations (1-3 ng/ml) that did not alter muscle DNA content
      and were not associated with a decrease in MHCf synthesis. TNF-alpha activated
      binding of nuclear factor kappaB (NF-kappaB) to its targeted DNA sequence and
      stimulated degradation of I-kappaBalpha, an NF-kappaB inhibitory protein. TNF
      alpha stimulated total ubiquitin conjugation whereas a 26S proteasome inhibitor
      (MG132 10-40 microM) blocked TNF-alpha activation of NF-kappaB. Catalase 1 kU/ml
      inhibited NF-kappaB activation by TNF-alpha; exogenous hydrogen peroxide 200
      microM activated NF-kappaB and stimulated I-kappaBalpha degradation. These data
      demonstrate that TNF-alpha directly induces skeletal muscle protein loss, that NF
      kappaB is rapidly activated by TNF-alpha in differentiated skeletal muscle cells,
      and that TNF-alpha/NF-kappaB signaling in skeletal muscle is regulated by
      endogenous reactive oxygen species.

PMID- 9657528
TI  - Sources of the neurotoxin quinolinic acid in the brain of HIV-1-infected patients
      and retrovirus-infected macaques.
AB  - This study investigated the sources of quinolinic acid, a neurotoxic tryptophan
      kynurenine pathway metabolite, in the brain and blood of HIV-infected patients
      and retrovirus-infected macaques. In brain, quinolinic acid concentrations in HIV
      infected patients were elevated by > 300-fold to concentrations that exceeded
      cerebrospinal fluid (CSF) by 8.9-fold. There were no significant correlations
      between elevated serum quinolinic acid levels with those in CSF and brain
      parenchyma. Because nonretrovirus-induced encephalitis confounds the
      interpretation of human postmortem data, rhesus macaques infected with retrovirus
      were used to examine the mechanisms of increased quinolinic acid accumulations
      and determine the relationships of quinolinic acid to encephalitits and systemic
      responses. The largest kynurenine pathway responses in brain were associated with
      encephalitis and were independent of systemic responses. CSF quinolinic acid
      levels were also elevated in all infected macaques, but particularly those with
      retrovirus-induced encephalitis. In contrast to the brain changes, there was no
      difference in any systemic measure between macaques with encephalitis vs. those
      without. Direct measures of the amount of quinolinic acid in brain derived from
      blood in a macaque with encephalitis showed that almost all quinolinic acid
      (>98%) was synthesized locally within the brain. These results demonstrate a role
      for induction of indoleamine-2,3dioxygenase in accelerating the local formation
      of quinolinic acid within the brain tissue, particularly in areas of
      encephalitis, rather than entry of quinolinic acid into the brain from the
      meninges or blood. Strategies to reduce QUIN production, targeted at
      intracerebral sites, are potential approaches to therapy.

PMID- 9657529
TI  - Apolipoprotein A-I production by chicken granulosa cells.
AB  - In avian species such as the chicken, development of the oocyte is associated
      with massive deposition of yolk in this cell. Oocytes grow within the follicle, a
      compartment consisting of a very specialized set of cells and acellular
      structures. The oocyte is surrounded by the perivitelline layer and granulosa
      cells, which are separated from the thecae by a pronounced basement membrane. In
      addition to the production of yolk precursors in the liver, we have long implied
      that cells within the follicle make a direct contribution to the growth of the
      oocyte. Here we show that chicken granulosa cells express and actively secrete
      apolipoprotein A-I (apoA-I) as a part of particles with very high density. The
      granulosa cell-derived, apoA-I-containing material is different from the small
      portion of yolk high density lipoprotein that arises via transfer from the
      peripheral circulation. We propose that the ApoA-I-containing particles secreted
      by granulosa cells 1) support the growth of the rapidly growing germ cell,
      possibly by direct lipid transfer to the plasma membrane of the oocyte, and/or 2)
      deliver cholesteryl esters to the steroid-producing cells of the theca layer.
      These findings are discussed with respect to the proposed functions of apoE (an
      apolipoprotein not found in chicken) within the mammalian follicle.

PMID- 9657530
TI  - Neuroprotection by bromocriptine against 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine-induced neurotoxicity in mice.
AB  - Mice were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 30
      mg/kg i.p. twice, 16 h apart). This resulted in changes in motor performance and
      toxic insult of nigral neurons as evidenced by dopamine depletion in nucleus
      caudatus putamen. In vitro and in vivo treatment of MPTP caused the generation of
      hydroxyl radicals (.OH) as measured by a sensitive salicylate hydroxylation
      procedure. A dopamine agonist, bromocriptine (10 microM and 10 mg/kg i.p.),
      blocked .OH formation caused by MPTP in vitro (20 microM) and in vivo (30 mg/kg
      i.p.). An MPTP-induced increase in the activity of catalase and superoxide
      dismutase in substantia nigra on the seventh day was reduced by bromocriptine
      pretreatment. Bromocriptine blocked MPTP-induced behavioral dysfunction as well
      as glutathione and dopamine depletion, indicating its potent neuroprotective
      action. This study suggests that bromocriptine stimulates antioxidant mechanisms
      in the brain and acts as a free radical scavenger in addition to its action at
      dopamine receptors, thus indicating its strength as a valuable neuroprotectant.

PMID- 9657532
TI  - The renin-angiotensin system: the centenary jubilee.

PMID- 9657531
TI  - The renin-angiotensin system--a century of progress.

PMID- 9657533
TI  - Normotensive offspring with non-dipper hypertensive parents have abnormal sleep
      pattern.
AB  - The objective of this study was to determine whether abnormal microstructure of
      sleep in non-dipper hypertensive patients was present in their offspring.
      Subjects included 11 normotensive offspring of non-dipper hypertensive parents
      (FH + ND), 6 of dipper hypertensive parents (FH + D) and 5 of normotensive
      parents (Controls). We measured blood pressure beat-to-beat by Finapres and all
      stages of sleep by polysomnographically recording simultaneously during
      spontaneous nocturnal sleep. We analysed blood pressure pattern for 4-min long
      random periods while the subjects were awake and during all stages of sleep;
      sleep efficiency (SE), sleep latency (SL), delta-sleep latency (delta-SL), REM
      sleep latency (REM-SL), Stage 1, Stage 2, Stage 3, Stage 4 and REM duration and
      percentage values, and microstructural aspects of sleep (arousal and microarousal
      temporization and features). FH + D and controls showed a fall in blood pressure
      greater than 10% in all stages of NREM sleep and in the FH + ND blood pressure
      fall in less than 10% of waking values in all NREM stages. REM sleep and heart
      rate were similar in the three groups during all stages of sleep. FH + ND showed
      the same number of arousals but more microarousals than FH + D and controls (p <
      0.0001). Microarousals induced several stage shifts through lighter sleep. For
      this reason, FH + ND spent more time in stage 2 than FH + D and controls. In
      conclusion, offspring of non-dipper hypertension parents showed a greater number
      of microarousals than the other two groups.

PMID- 9657534
TI  - Prognosis during five years of follow-up among patients admitted to the emergency
      department with acute chest pain in relation to a history of hypertension.
AB  - AIM: To describe the mortality, mode and place of death and risk indicators of
      death during 5 years of follow-up among patients admitted to the emergency
      department (ED) with acute chest pain or other symptoms raising a suspicion of
      acute myocardial infarction (AMI) in relation to a history of hypertension.
      METHODS: All the patients admitted to the ED at Sahlgrenska University Hospital
      during a period of 21 months with acute chest pain or other symptoms raising a
      suspicion of AMI were followed up prospectively for 5 years. RESULTS: Of 5,355
      patients fulfilling the inclusion criteria, 22% had a history of hypertension.
      Hypertensive patients differed from non-hypertensive patients in that there were
      more females, they were older and had a higher prevalence of previous
      cardiovascular disease. Patients with a history of hypertension had a 5-year
      mortality rate of 37.4% as compared with 22.2% among non-hypertensive patients (p
      < 0.001). The difference in mortality appeared to be more marked among patients
      without a history of cardiovascular disease. A history of hypertension was an
      independent predictor of death. Risk indicators of death appeared to be
      relatively similar among patients with and without a history of hypertension. Of
      the patients who died, those with a history of hypertension were more frequently
      judged to have suffered a cardiac death and died more frequently in association
      with an AMI. CONCLUSION: Among patients admitted to the ED with acute chest pain
      and with a history of hypertension, 37% died during the following 5 years. A
      history of hypertension was an independent predictor of death.

PMID- 9657535
TI  - Insulin-like growth factor binding protein-1 as a marker of the metabolic
      syndrome--a study in borderline hypertension.
AB  - AIM: To evaluate insulin-like growth factor I (IGF-I) and insulin-like growth
      factor binding protein-1 (IGFBP-1) in borderline hypertension (BHT) in relation
      to plasma lipoprotein and insulin levels, anthropometric variables and 24-h
      ambulatory blood pressure (BP). Seventy-five BHT men diastolic BP (DBP) 85-94
      mmHg) and 75 age-matched normotensive controls (NT, DBP < or = 80 mmHg) were
      recruited from a population-based screening program. RESULTS: There was no
      difference in IGF-I or IGFBP-1 between BHT and NT men. However, subjects with
      insulin resistance (IR) had decreased levels of IGF-1 (145 +/- 36 vs 153 +/- 28
      microg/L, p < 0.05) and IGFBP-1 (41 +/- 15 vs 52 +/- 20 microg/L, p < 0.01)
      compared to those without IR. IGF-I correlated inversely to BP levels in the BHT
      group (r = -0.24 to -0.28, p < 0.05). IGFBP-1 correlated inversely with BMI,
      lipoprotein and insulin levels (r = -0.29 to -0.48, p < 0.01), independent of IR.
      CONCLUSION: While there are no differences between BHT and NT men in IGF-I and
      IGFBP-1, both are significantly decreased in IR subjects. IGFBP-1 exhibits a
      close correlation to metabolic factors. Decreased IGFBP-1 could thus be suggested
      as a variable marking the "metabolic syndrome" of hypertension.

PMID- 9657536
TI  - Effects of isolated systolic hypertension and essential hypertension on large and
      middle-sized artery compliance.
AB  - BACKGROUND: Systolic hypertension of the elderly is characterized by a reduction
      in arterial compliance. Whether and to what extent this involves arteries of
      various structure and size is not well known. OBJECTIVE: To study carotid and
      radial artery compliance in systolic hypertension of the elderly, compared to
      essential hypertension and normotension. METHODS: We investigated 28 elderly
      patients with systolic hypertension (age 68.6 +/- 1.4 years, mean +/- SE;
      systolic blood pressure > 160 mmHg and diastolic blood pressure < 90 mmHg) plus
      17 age-matched patients with essential hypertension and 15 age-matched healthy
      normotensive subjects. Radial and carotid artery compliance were evaluated using
      echotracking techniques. In both arteries compliance was assessed statistically
      and dynamically, i.e. as compliance values throughout the diasto-systolic
      pressure range. Measurements included intima-media wall thickness of the radial
      artery. RESULTS: Compared to normotensive subjects, carotid artery compliance was
      reduced in essential hypertension and more so in systolic hypertension. However,
      although in both groups radial artery wall thickness was markedly greater than in
      the normotensive group, radial artery compliance was markedly reduced in systolic
      hypertension, but unchanged in essential hypertension. CONCLUSIONS: In systolic
      hypertension of the elderly the reduction of arterial compliance is marked in
      both muscular and large elastic arteries, while in elderly essential
      hypertensives changes in arterial compliance are more heterogeneous, i.e. only
      carotid artery compliance is reduced. The different effects of these two types of
      hypertension on arterial mechanics are visible throughout the physiological range
      of blood pressure and probably accounted for by different alterations in vessel
      wall structure.

PMID- 9657537
TI  - The diurnal variation in blood pressure should be calculated from individually
      defined day and night times.
AB  - The aim of this study was to compare the nocturnal fall in BP parameters
      calculated from individually defined periods of day and night to values computed
      from collectively fixed day/night definitions. Day and night periods were defined
      according to 3 different methods: (i) the individually defined time of getting up
      and going to bed obtained from participant diaries (MethodIND); (ii) the mean
      time of rising and retiring in the group (MethodMEAN); and (iii) a daytime period
      from 07.00-22.00 h as recommended by The Scientific Committee (Method722). The
      ambulatory BP was recorded every 30 min over 24 h. One hundred and eighty-seven
      persons aged 40-66 years participated. With MethodIND, the BP load, systolic,
      diastolic and mean BPs were higher in the daytime and lower in the night-time
      compared to the results using Method722 and MethodMEAN. The nocturnal BP fall
      using MethodIND was larger than the fall calculated from every possible fixed
      division in the period from 3 h before till 3 h after the group mean time of
      getting up and going to bed (p < 0.001). The lowest frequency of non-dipping,
      defined as a nightly fall in systolic and diastolic BP below 10%, was observed
      using MethodIND (10%). Compared to MethodIND, 11% were misclassified as non
      dippers by Method722 and 8% by MethodMEAN. We conclude that the diurnal blood
      pressure variation based on individually defined periods of day and night is
      larger than the variation based on any collectively fixed day/night definition.
      It is recommended that assessment of the nocturnal change in BP be based on
      individually defined periods of day and night.

PMID- 9657538
TI  - Effects of amlodipine and lisinopril on left ventricular mass and diastolic
      function in previously untreated patients with mild to moderate diastolic
      hypertension.
AB  - The aim of the study was to compare the effects of two long-acting
      antihypertensive agents, the calcium-antagonist amlodipine and the ACE inhibitor
      lisinopril, on left ventricular mass and diastolic filling in patients with mild
      to moderate diastolic hypertension from primary care centres. It is a 1-year
      prospective, double-blind, randomized, parallel group, comparative study.
      Patients between 25 and 75 years of age with untreated hypertension with elevated
      diastolic blood pressure (> or = 95 mmHg) on three occasions (twice on the first
      visit and once only on the second and third visits) were recruited from a
      population survey. After 4 weeks placebo run-in 71 patients were randomized to
      dosages of amlodipine 5-10 mg or lisinopril 10-20 mg, which were titrated on the
      basis of the effects on blood pressure. Fifty-nine patients completed the study
      period. Primary endpoints were left ventricular mass index and early to atrial
      peak filling velocity. Office and ambulatory blood pressure and other
      echocardiographic measurements were considered secondary. Decrease in blood
      pressure was equal for both treatment regimens. A statistically significant
      decrease in left ventricular mass index in both treatment groups was observed: 
      11.0 g/m2 (95% CI: -6.0, -16.1) in the amlodipine group and -12.6 g/m2 (95% CI: 
      8.2, -17.0) in the lisinopril group. The higher the baseline value of left
      ventricular mass before treatment, the more the decrease after treatment. Early
      to atrial peak filling velocity did not change significantly within the treatment
      groups: +0.07 (95% CI: -0.01, +0.15) in the amlodipine group and +0.01 (95% CI: 
      0.06, +0.08) in the lisinopril group. However, analysis of time measurements of
      the early peak showed significant changes for both treatment groups. No
      significant differences in primary and secondary endpoints between treatment
      groups were found. Twelve patients did not complete the study, seven in
      amlodipine and five in lisinopril, basically due to adverse events. The effects
      of amlodipine and lisinopril on left ventricular mass and early to atrial filling
      peak velocity after 1 year of treatment in patients with previously untreated
      mild to moderate hypertension are similar. Further studies are recommended,
      particularly with a larger sample size and a follow-up of longer duration.

PMID- 9657539
TI  - Regression of left ventricular wall thickness during ACE-inhibitor treatment of
      essential hypertension is associated with an increase in insulin mediated
      skeletal muscle blood flow.
AB  - Left ventricular hypertrophy (LVH) has been associated with insulin resistance, a
      condition with an impaired insulin-mediated vasodilation in skeletal muscle. ACE
      inhibitors have been reported to be superior to most other antihypertensive drugs
      in inducing a regression of LVH. In a double-blind study with parallel groups, 50
      patients with essential hypertension were randomized to treatment with either
      fosinopril (20 mg o.d.) or atenolol (50 mg o.d.) for 12-16 weeks. Left ventricle
      wall thickness (LVWT, defined as the sum of interventricular septum and posterior
      wall), diastolic function (represented by the ratio between the E-wave and the A
      wave of mitral blood flow) and femoral artery blood flow (FBF) were evaluated
      using ultrasonic measurements. FBF was measured at normoinsulinemia and after 2 h
      of euglycemic hyperinsulinemia. Before treatment, the insulin-induced increase in
      FBF was inversely related to the LVWT (r = -0.52, p < 0.02). The reduction in
      ambulatory 24-h SBP/DBP was 13/9 mmHg for fosinopril and 15/14 for atenolol,
      ambulatory DBP being significantly more reduced by atenolol (p = 0.03 for
      difference in treatment effect). However, only fosinopril treatment resulted in a
      significant reduction in LVWT (from 20.5 mm to 19.4 mm, p < 0.05). The degree of
      reduction in LVWT was related to the increase in FBF in the fosinopril group (r =
      -0.45, p < 0.05). For fosinopril (but not for atenolol), there was a positive
      relationship between the change in E/A ratio and the change in femoral artery
      stroke volume (r = 0.80, p < 0.01). CONCLUSION: Impaired insulin-induced
      stimulation of leg blood flow was related to an increased LVWT. Furthermore,
      during fosinopril treatment, regression of LVWT was associated with enhanced
      skeletal muscle blood flow during hyperinsulinemia. This indicates that impaired
      peripheral blood flow (and thereby increased afterload) may be a possible
      mechanism explaining the previously found association between insulin resistance
      and cardiovascular hypertrophy.

PMID- 9657540
TI  - Video-assisted thoracoscopic excision of herniated thoracic disc: description of
      technique and preliminary experience in the first 29 cases.
AB  - This study evaluates the technique and results of video-assisted thoracoscopic
      surgery (VATS) for the treatment of symptomatic thoracic disc herniation. Results
      were compared with a literature review of open surgical techniques of thoracic
      disc excision with regard to efficacy, safety, and surgical outcomes. VATS has
      recently been described for thoracic surgery as having the advantage of decreased
      postoperative pain and morbidity, faster patient recovery, and shortened
      intensive care unit (ICU) hospitalization. Twenty-nine consecutive patients
      underwent VATS for symptomatic thoracic disc herniation. Herniations ranging from
      T5-6 to T12-L1 were successfully approached by using a three- or four-portal
      strategy. Postoperative magnetic resonance imaging (MRI) scans were evaluated.
      Pre- and postoperative Oswestry Disability Questionnaires and Linear Analog Pain
      Scale data were obtained. Patients were grouped according to presenting symptoms.
      The minimal follow-up was 1 year (range, 12-24 months). Mean operative time was
      175 min for 29 patients. Significant improvement (p < 0.01, paired t test) was
      recorded in Oswestry Disability Questionnaires and Linear Analog Scale Tests. Of
      the patients, 75.8% (22) were satisfied, 3.4% (one) unsatisfied, with 20.1% (six)
      unchanged. Narcotic use was significantly eliminated or reduced. Mean return to
      work was 5 weeks (private insurance) and 21 weeks (workers compensation). The
      surgical and postoperative complication rate was 13.8%. VATS appears to be a safe
      and efficacious method of excising herniated thoracic discs. Follow-up results at
      1 year resulted in high patient satisfaction. VATS advantages include decreased
      length of hospitalization as well as improved patient comfort.

PMID- 9657541
TI  - Neurologic deterioration after cervical spinal cord injury.
AB  - Neurologic deterioration after cervical spinal cord injury (SCI) at a regional
      spinal cord center was examined. This study examined the incidence of neurologic
      deterioration as well as associated risk factors in our patient population. Up to
      5.8% of cervical SCI patients have been noted to deteriorate neurologically after
      admission. Risk factors have been early surgery, halo application, traction, and
      Stryker frame rotation. All cervical SCI patients admitted between 1978 and 1993
      who had neurologic deterioration were studied for characteristics of their event,
      operative status, risk factors, mortality, and neurologic return at 1 year
      postinjury. Patients were divided into minor and major groups based on the degree
      of neurologic loss. Nineteen of 1,031 patients were identified as neurologically
      deteriorated (1.84%). There were 8 major and 11 minor group patients. The average
      time from injury to deterioration was 3.95 days. Of 10 patients undergoing
      surgery at < or =5 days, 8 deteriorated postoperatively. Potential risk factors
      were ankylosing spondylitis (three patients), sepsis (four patients), and
      intubation (four patients). Neurologic recovery at 1 year showed that 11 of 12
      patients were improved. Neurologic deterioration occurred in 1.84% of our
      patients. Deteriorations were associated with surgery at <5 days after injury,
      ankylosing spondylitis, sepsis, and intubation.

PMID- 9657542
TI  - Accuracy of SPECT scanning in diagnosing pseudoarthrosis: a prospective study.
AB  - The present study attempted to analyze the efficacy of single photon emission
      computed tomography (SPECT) in diagnosing pseudoarthrosis after fusion using
      surgical exploration as the gold standard. This study examined the SPECT scans of
      38 patients before they underwent surgical exploration of their fusion mass for
      suspected pseudoarthrosis or in conjunction with instrumentation removal.
      Surgical findings were compared with the radiologists' findings to determine the
      efficacy of SPECT in diagnosing pseudoarthrosis. Radiographic determination of
      pseudoarthrosis has been difficult after attempted fusion of the spine. Multiple
      radiographic modalities have been touted as accurate depicters of the failure of
      spinal fusion. However, no method has been found to be highly accurate in the
      clinical setting. Thirty-eight patients (mean age = 42.8, 21 males/17 females, 35
      of 38 with instrumentation) underwent SPECT scans before surgical exploration of
      their fusion mass for suspected pseudoarthrosis or in conjunction with
      instrumentation removal as part of this prospective study. The average interval
      from their fusion procedure until their SPECT scan was 23.9 months (range, 9-120
      months). All surgical findings were recorded with regard to solidity of the
      fusion and the level of the possible pseudoarthrosis. All SPECT scans were read
      at a time after surgery by an independent nuclear radiologist who had not read
      their SPECT scans before surgery and who did not know the results of exploration.
      Results of the radiologist's reading were then compared with surgical exploration
      findings, and sensitivity and specificity was calculated. There were 24 solid
      fusions and 14 pseudoarthroses. SPECT scans correctly identified 7 of the 14
      pseudoarthroses and 14 of the 24 solid fusions. This represents a sensitivity of
      0.50 and a specificity of 0.58. SPECT scanning correctly diagnosed the one solid
      fusion and two pseudoarthrosis patients in the three patients who had no
      instrumentation. This study demonstrates that SPECT scanning alone is inaccurate
      in diagnosing pseudoarthrosis when using surgical exploration as the gold
      standard. Given recent pressures for cost containment, we cannot recommend SPECT
      scanning as a routine modality for use in the diagnosis of pseudoarthrosis. We
      cannot define the accuracy of SPECT scanning used together with computed
      tomography scans, plain films, or other radiographic modalities in the diagnosis
      of pseudoarthrosis.

PMID- 9657543
TI  - Circumferential surgery for the management of cervical ossification of the
      posterior longitudinal ligament.
AB  - Can simultaneous anterior and posterior (circumferential) surgery in patients
      with cervical ossification of the posterior longitudinal ligament
      (OPLL)/stenosis, achieving both decompression and stabilization, be accomplished
      with acceptable risk? Between 1989 and 1996, 22 circumferential procedures were
      performed, including an average 2.5-level anterior corpectomy with 5-level
      posterior wiring and fusion. These patients were severely myelopathic (average
      Nurick grade 3.5) and were followed for a mean interval of 22 months (range 4-52
      months). Circumferential procedures required an average of 9.8 h and 3.5 U of
      blood transfused. Postoperatively, patients improved approximately +3.0 Nurick
      grades. Simultaneous circumferential surgery for OPLL/stenosis may be
      successfully performed in <10 h with limited blood loss.

PMID- 9657544
TI  - Circumferential surgery for the management of cervical ossification of the
      posterior longitudinal ligament.

PMID- 9657545
TI  - Evaluation of computed tomographic methods to measure vertebral rotation in
      adolescent idiopathic scoliosis: an intraobserver and interobserver analysis.
AB  - The purpose of this study was to compare three computed tomography (CT)
      measurement methods that have been described by Aaro-Dahlborn, Ho, and Krismer et
      al. The methods were based on clinical, intraobserver, and interobserver
      analysis. Twenty-five patients with adolescent idiopathic scoliosis were studied
      for clinical reliability of these methods. There was a significant correlation
      between Aaro-Dahlborn and Ho's methods (p < 0.02), and there was no correlation
      between Krismer's method and the other two (p > 0.05). Intraobserver analysis was
      performed by one observer at 20 different times, and interobserver analysis was
      performed by 20 orthopedic surgeons on the same CT scan. Intraobserver and
      interobserver analysis has shown that the method described by Ho is the most
      reliable one. Consequently, Ho's method is the most reliable and clinically the
      most useful method for measuring the vertebral rotation in adolescent idiopathic
      scoliosis.

PMID- 9657546
TI  - Biomechanical study of lumbar pedicle screws: does convergence affect axial
      pullout strength?
AB  - We tested the hypothesis that two pedicle screws placed in convergence offer more
      resistance to axial pullout than do two pedicle screws placed in parallel. Eight
      fresh cadaveric lumbar spines, L2-L5, were harvested. Individual vertebra were
      then paired for testing. Into each L2 and L3 vertebra, a pair of pedicle screws
      were inserted. The screws were placed parallel (i.e., at 0 degrees convergence)
      in L2 and at 30 degrees convergence in L3, in the first pair. In the second pair
      of L2 and L3, this order was reversed. Alternating the convergence angle was
      carried out on each successive pair of L2 and L3. A section of standard
      longitudinal rod was attached to each pedicle screw by using top-loading three
      point shear clamp fixation with tangential lock screws. Transverse connectors
      were attached superiorly and inferiorly to the longitudinal rods. As in L2 and
      L3, each L4 and L5 received a pair of screws placed at either 0 or 30 degrees
      convergence, with the angle of convergence alternated on each successive pair.
      Each pair of screws in each vertebra was tested in axial pullout at 1 mm/s.
      Fourteen pairs of vertebra were tested and two findings emerged: paired pedicle
      screws at 30 degrees of convergence offered more resistance to axial pullout
      (28.6% on average) and sustained higher loads at the clinical threshold of
      loosening (101% on average) than paired pedicle screws placed in parallel. Thus
      there seems to be an advantage to screws placed in 30 degrees of convergence as
      compared with screws in parallel.

PMID- 9657547
TI  - Effects of cross-linkage on fatigue life and failure modes of stainless steel
      posterior spinal constructs.
AB  - This study tested the effects of cross-linkage on the fatigue performance of
      posterior spinal constructs (i.e., AcroMed stainless steel Isola systems). The
      failure modes encountered during fatigue were also examined. The results of this
      study confirmed earlier findings that the use of cross-linkage does not
      significantly affect the stability of posterior constructs during axial loading.
      Their influence in torsion loading is much more pronounced. During the fatigue
      tests, posterior stainless steel spinal implants instrumented without cross
      linkage reached 1 million cycles at 500- and 750-N loads. When the load was
      increased to 1,000 N, the number of cycles to failure dropped by two-thirds.
      These findings demonstrate that the endurance limit was between 750 N and 1,000 N
      for spinal constructs without cross-linkage, with the limit being closer to 750
      N. Devices equipped with one or two cross-linkages reached 1 million cycles at
      500 N. The number of cycles to failure dropped dramatically as the load was
      increased to 750 and 1,000 N. It appears that the endurance limits for spinal
      devices using cross-linkage should be 500 and 750 N, with the limit closer to the
      500-N load. All rod fractures occurred near the junction between the longitudinal
      and transverse rods. Stress concentration was greatly in the vicinity of that
      contact point. These results should provide a basis for future improvement in
      endurance limits of spinal implants equipped with cross-linkage. Higher endurance
      limits will reduce the toxic effects encountered during fracture modes. The
      implants will also be better able to withstand the high physiologic loads
      experienced by obese individuals.

PMID- 9657548
TI  - Capsular ligament stretches during in vitro whiplash simulations.
AB  - Clinical symptoms of whiplash are presently not well understood. Injuries to
      capsular and other spinal ligaments of the cervical spine during trauma are a
      possible pathomechanism that could explain some aspects of the whiplash symptom
      complex. This study quantified the elongations of capsular ligaments (CLs) at all
      cervical spinal levels during whiplash simulation using an in vitro model. Seven
      fresh human cadaveric specimens (occiput-C7 or T1) were carefully dissected,
      preserving the osteoligamentous structures. Spinal ligament transducers were
      attached across the CLs from C2-C3 to C6-C7 in each specimen, alternating the two
      sides. Physiological elongations of the CLs were measured with a standard
      flexibility test using 1 Nm of pure moments. Next, the specimen was fitted with a
      surrogate head representing 50th percentile human head. The specimen was mounted
      on a sled designed to simulate whiplash and subjected to 2.5, 4.5, 6.5, 8.5, and
      10.5 g (1 g = 9.81 m/s2) horizontal accelerations sequentially. The dynamic
      elongations of the CLs were continuously recorded during the entire trauma and
      were later converted to strains. There were modest increases in capsular ligament
      strains during the trauma over the maximum physiological values. The two largest
      peak strains of 29.5 and 35.4% were seen at C6-C7 during the 6.5- and 10.5-g
      accelerations. We did not find strong correlation between the strain during the
      trauma and the trauma sled acceleration.

PMID- 9657549
TI  - Anatomic considerations of the vertebral artery: implications for anterior
      decompression of the cervical spine.
AB  - Anatomic dissection and measurements of the vertebral artery relative to the
      medial margin of the longus colli and the anterior margin of the vertebral body
      from C6 to C3 were performed in this study. The average angle of the vertebral
      artery relative to the midline was 4.3 +/- 2.6 degrees overall. The average
      distance between the medial margin of the longus colli and medial margin of the
      vertebral artery gradually decreased from the C6 level (11.5 +/- 1.0 mm) to the
      C3 level (9.0 +/- 1.3 mm). The average distance between anterior margin of the
      vertebral body and anterior margin of the vertebral artery gradually increased
      from the C6 level (7.2 +/- 1.9 mm) to the C3 level (9.6 +/- 2.1 mm). The distance
      between medial borders of the longus colli muscles gradually decreased from the
      C6 level (13.8 +/- 2.2 mm) to the C3 level (7.9 +/- 2.2 mm). Relative to the
      medial margin of the longus colli muscle and the anterior margin of the vertebral
      body, the vertebral artery is more lateral and anterior at the C6 level but more
      medial and posterior at C3 level. This knowledge may facilitate effective
      decompression of the lateral cervical canal and improve the margin of safety of
      the surgeon.

PMID- 9657550
TI  - Modified Magerl technique of lateral mass screw placement in the lower cervical
      spine: an anatomic study.
AB  - Twelve adult embalmed cadaveric cervical spines were used to modify the
      traditional Magerl technique for screw placement in the lower cervical spine. The
      starting point for the drill bit was 2 mm inferior to the inferiormost edge of
      the superior facet and 1-2 mm medial to the posterior midline of the lateral
      mass. The orientation of the drill bit was parallel to the superior facet in the
      sagittal plane, and 25-30 degrees lateral in the transverse plane. After
      drilling, we made direct measurements of the screw path length between the dorsal
      and ventral cortexes of the lateral mass and screw-path angles in both the
      sagittal and transverse planes. The results showed the mean screw-path length for
      all levels ranged from 11 to 15 mm with the smallest value at C7. The mean
      sagittal and transverse angles of the screw path ranged from 41 to 43 degrees and
      from 26 to 28 degrees. Penetration of the superior facet was found in three
      (2.5%) cases. Possible spinal nerve violation was seen in 13 (10.8%) cases if the
      drill bit was excessively overpenetrated. This study suggested that our modified
      Magerl technique for lateral mass screw placement be as high as possible without
      impinging on the facet joint, and drilling be as cranial and lateral as possible
      to leave the superior articular process as high and lateral as possible. This may
      further decrease the incidence of spinal nerve injury. Careful drilling and
      tapping technique is recommended to avoid overpenetration.

PMID- 9657551
TI  - Finite element analysis of the lower lumbar neural arch under facet loading.
AB  - To evaluate the mechanical effect of the direction of facet load on the isthmus
      stresses of the lower lumbar neural arch, stress analyses were performed by using
      three-dimensional finite element models of isolated L4 and L5 vertebrae with
      particular emphasis on accurate discretization of the posterior elements. The
      bilateral symmetric or unilateral facet loads, with a constant magnitude, were
      applied within the sagittal and transverse planes. The largest maximal principal
      stress in the neural arch (the largest sigma(max)) tended to be qualitatively
      similar in L4 and L5. At the physiologic range, the largest sigma(max), observed
      on the anterior surface of the isthmus, was relatively insensitive to the
      sagittal plane loadings but sensitive to the transverse plane loadings. The
      values of the largest sigma(max) of L4 and L5 were low at the more frontally
      directed facet load. The magnitude and direction of the largest sigma(max)
      depended upon the facet loadings mainly on the ipsilateral side and partly on the
      opposite side. The results suggest that the direction of facet load, which may be
      characterized by the facet orientation, can have mechanical effects on the
      occurrence and direction of isthmic crack.

PMID- 9657552
TI  - Nitric oxide: a possible etiologic factor in spinal cord cavitation.
AB  - To determine whether nitric oxide (NO) is related to spinal cord cavitation, we
      treated mice that underwent spinal cord injury with NG-mono-methyl-L-arginine (N
      MMA). Spinal cord specimens were subjected to glial fibrillary acidic protein
      (GFAP) immunostaining, which is selective for astrocytes. Spinal cord cavities
      and GFAP-positive glial cells appeared simultaneously at 3 days after spinal cord
      injury, and the cavities enlarged at 7 days. In mice receiving N-MMA, the
      cavities were significantly smaller than those in the mice that underwent spinal
      cord injury only. However, the numbers of GFAP-positive cells showed no
      difference between these two groups. These experimental findings suggest that
      cavitation of the spinal cord is caused mainly by NO released from activated
      glial cells.

PMID- 9657553
TI  - Proteoglycans in the nucleus pulposus of canine intervertebral discs after
      chondroitinase ABC treatment.
AB  - Experimental chemonucleolysis of the canine intervertebral disc with
      chondroitinase ABC and chymopapain was compared during a 52-week period.
      Roentgenograms and magnetic resonance imaging were used to examine changes in
      disc space and water content, respectively. Disc space narrowing and reductions
      in disc water content after chondroitinase ABC treatment were less than that
      after chymopapain. High-performance liquid chromatography was performed to
      measure changes in proteoglycans. Similarly to chymopapain, chondroitinase ABC
      degrades proteoglycans in the nucleus pulposus and decreases their quantity.
      However, large differences in the molecular weight and acidity of the
      resynthesized proteoglycans and in the chain length of the resynthesized
      glycosaminoglycans were observed between the two enzymes. The difference in disc
      space narrowing and the changes in disc water content between the two enzymes
      might result from differences in the characteristics of the resynthesized
      proteoglycans.

PMID- 9657554
TI  - Mechanical modulation of intervertebral disc thickness in growing rat tails.
AB  - Progression of scoliosis deformity during growth is thought to be caused by
      asymmetrical loading, resulting in asymmetrical growth with vertebral and disc
      wedging in a "vicious cycle." The purpose of this study was to quantify the
      changes in disc thickness during growth in rat tails subjected to compression or
      distraction loading for 6 or 9 weeks, to investigate the hypothesis that disc
      growth is mechanically modulated. Six-week-old Sprague-Dawley rats were studied
      with compression loading (13 animals) or distraction loading (15 animals) applied
      to their tails, and there were 8 sham animals. Loading was applied to tail
      segments by means of an external ring fixator. Radiographic measurements of disc
      thickness were made at biweekly intervals. From the initial to final radiograph,
      compressed discs had reduced thickness averaging (+/-SD) 0.50 +/- 0.28 mm,
      distraction discs had average increased thickness of 0.20 +/- 0.42 mm, and sham
      discs lost an average of 0.21 +/- 0.18 mm of thickness (analysis of variance p <
      0.001). There was an "initial change" in disc thickness averaging 0.18 +/- 0.32
      mm in nonloaded discs, which was similar in magnitude to the elastic deformation
      and was attributed to disc swelling under anesthesia. These results indicate that
      growth in disc thickness is mechanically modulated by axial loading in growing
      rats.

PMID- 9657555
TI  - Cervical spondylitic myelopathy: plates in anterior recompression and
      reconstruction.

PMID- 9657556
TI  - Direct amplification of Mycobacterium tuberculosis deoxyribonucleic acid in
      paucibacillary tuberculosis.

PMID- 9657557
TI  - Pulmonary fibrosis: cytokines in the balance.
AB  - Pulmonary fibrosis can complicate diverse pulmonary and systemic pathologies. In
      many cases the underlying cause remains unidentified. Mortality from the disease
      is increasing steadily in the UK and USA. The clinical features are well
      described, but patients frequently present at an advanced stage, and current
      treatments have not improved the poor prognosis. There is a compelling need to
      identify the fibrotic process earlier and to develop new therapeutic agents.
      Increased collagen deposition is central to the pathology and interest over the
      last decade has focused on the role of cytokines in this process. These
      polypeptide mediators are believed to be released from both circulating
      inflammatory and resident lung cells in response to endothelial and epithelial
      injury. Key cytokines currently implicated in the fibrotic process are
      transforming growth factor-beta, tumour necrosis factor-alpha and endothelin-1.
      This article outlines the evidence implicating these mediators in the
      pathogenesis of pulmonary fibrosis and also considers the possible role of
      cytokines with antifibrotic effects, such as interferon-gamma. The "balance" of
      positively and negatively regulating cytokines is discussed, and the potential
      for interaction with other factors including viruses, hormones and altered
      antioxidant status is also considered. Finally, potential novel therapeutic
      approaches are discussed, together with suggestions for future studies and
      clinical trials. As the outcomes of different avenues of research over the last
      ten years are brought together, it is clear that there is now a hitherto
      unrivalled opportunity to begin to tackle the treatment of this devastating
      disease.

PMID- 9657558
TI  - Clinical utility of the polymerase chain reaction in the diagnosis of
      extrapulmonary tuberculosis.
AB  - This study examines the diagnostic utility of the polymerase chain reaction (PCR)
      in 156 patients (five human immunodeficiency virus (HIV) seropositive) suspected
      of extrapulmonary tuberculosis. The results of PCR in 226 samples from 11
      different sites were compared with the results of microscopy and culture.
      Positive culture results were predicted in 86% of samples by PCR but in only 31%
      by microscopy. Specificity of PCR was 92%. In cases with culture-proven
      tuberculosis, PCR identified all 11 microscopy positive cases and 19 of 24 (79%)
      of the microscopy-negative cases. In four patients, PCR excluded the diagnosis of
      tuberculosis in microscopy-positive samples, which were later shown to contain
      mycobacteria other than Mycobacterium tuberculosis or laboratory contaminants. In
      20 patients (microscopy, PCR and culture negative) a trial of antituberculous
      drugs was given, but patients showed no improvement and treatment was stopped. In
      17 patients, all culture negative (in nine PCR was positive, three of whom also
      had positive microscopy) the diagnosis was probable tuberculosis based on
      clinical findings and response to treatment. This polymerase chain reaction has a
      much higher sensitivity than microscopy and can facilitate therapeutic decisions
      for those with suspected extrapulmonary tuberculosis.

PMID- 9657559
TI  - Analysis of BAL fluid in M. avium-intracellulare infection in individuals without
      predisposing lung disease.
AB  - The purpose of this study was to investigate the characteristics of pulmonary
      inflammation caused by Mycobacterium avium-intracellulare (MAI) in individuals
      with neither predisposing lung disease nor immunodeficiency. We reviewed the
      records of 20 patients with pulmonary MAI infection (including 19 female
      patients) whose past history and previous chest radiographs revealed no
      predisposing lung disease. We analysed the bronchoalveolar lavage fluid (BALF)
      from these 20 patients and from six normal female controls. The BALF was
      recovered directly from the relevant segment that was identified with chest
      computed tomography. The BALF cell profiles showed significantly elevated counts
      for total cells, lymphocytes and neutrophils, but the macrophage cell count was
      not elevated. The CD4+ lymphocyte count and CD4+/CD8+ ratio were significantly
      increased compared with those in the controls. The lymphocytes demonstrated
      phenotypical evidence of activation, with increased expression of human leukocyte
      antigen-D-related antigen (HLA-DR). The tumour necrosis factor-alpha, interleukin
      (IL)-1beta, IL-6 and IL-8 concentrations were significantly increased. The
      neutrophil elastase concentration was also increased, and it was significantly
      correlated with the neutrophil cell count in the BALF. These findings suggest
      that the increased counts of activated CD4+ lymphocytes and neutrophils and the
      elevated concentrations of proinflammatory cytokines and neutrophil elastase
      appear to be common characteristics in Mycobacterium avium-intracellulare
      infection.

PMID- 9657560
TI  - Montelukast, a potent leukotriene receptor antagonist, causes dose-related
      improvements in chronic asthma. Montelukast Asthma Study Group.
AB  - The leukotrienes are known to be important mediators of bronchial asthma. The
      ability of montelukast, a potent and selective CysLT1 leukotriene receptor
      antagonist, to cause a dose-related improvement in chronic asthma was
      investigated in a placebo-controlled, multicentre, parallel-group study. After a
      two week placebo run-in period, chronic asthmatic patients with a forced
      expiratory volume in one second (FEV1) 40-80% predicted with > or = 15% increase
      (absolute value) after beta2-agonist were randomly assigned to one of four
      treatment groups (placebo or montelukast 2, 10, or 50 mg once daily in the
      evening) for a three week, double-blind treatment period. For patient-reported
      end-points (daytime symptom score, use of as needed inhaled beta2 agonist, asthma
      specific quality of life) and frequency of asthma exacerbations, montelukast 10
      and 50 mg caused similar responses, superior to 2 mg and significantly (p<0.05;
      linear trend test) different from placebo. All three doses caused improvements in
      FEV1 and morning and evening peak expiratory flow rate (PEFR) that were
      significantly (p<0.05) different from placebo. Differences (least square mean)
      between the pooled 10 and 50 mg montelukast treatment groups and placebo were:
      7.1% change from baseline in FEV1, 19.23 L x min(-1) in morning PEFR, -0.29 in
      daytime asthma symptom score (absolute value), and -0.82 in beta2-agonist use
      (puff x day(-1)). The incidence of adverse experiences was neither dose-related
      nor different between montelukast and placebo treatments. We conclude that
      montelukast causes a dose-related improvement in patient-reported asthma end
      points over the range 2-50 mg. Montelukast causes benefit to chronic asthmatic
      patients by improving asthma control end-points.

PMID- 9657561
TI  - Effect of low-dose beclomethasone dipropionate on asthma control and airway
      inflammation.
AB  - The effects of usual or low doses of inhaled corticosteroids on airway mucosal
      inflammation have not yet been examined. We therefore, compared the effects of
      inhaled beclomethasone dipropionate (BDP) 336 microg x day(-1) on asthma control
      outcomes and markers of airway inflammation. Twenty-four adult subjects with mild
      and moderate asthma were randomized to receive either BDP or placebo for four
      weeks; then subjects entered a single blind four week placebo run-in period. We
      found that the BDP group had significantly greater improvements in forced
      expiratory volume in one second (FEV1), morning peak flow, and rescue salbutamol
      use than the placebo-treated group. The improvement in FEV1 largely reversed one
      week after treatment was stopped. The decrease in the median percentage of
      eosinophils in induced sputum in the BDP group from 3.8% to 3.4% was not
      significant, but because eosinophils increased from 8.4% to 12.7% in the placebo
      group, there was a significant difference between treatment groups (p=0.03).
      There was no significant difference between groups during treatment in the levels
      of eosinophil cationic protein (ECP), tryptase mucin-like glycoprotein, or
      fibrinogen in induced sputum. The change in FEV1 in the BDP group did not
      correlate significantly with the change in eosinophil percentage or ECP levels.
      We concluded that four weeks of treatment with inhaled beclomethasone
      dipropionate 336 microg x day(-1) was associated with significant improvements in
      peak flow, forced expiratory volume in one second, and rescue salbutamol use in
      asthmatic subjects but was not associated with large reductions in markers of
      eosinophilic inflammation, bronchovascular permeability, or mucus hypersecretion.

PMID- 9657562
TI  - Novel adaptation of a method to assess responsiveness of bronchial segments in
      vitro.
AB  - In vivo agonist delivery to the lungs is characterized by absorption through the
      mucosal layer followed by access to the smooth muscle. When agonists are applied
      to perfused bronchial segments, a difference in potency to agonists applied to
      the serosal (outside) or mucosal (inside) surface can be demonstrated. In order
      to elucidate this effect in canine bronchial segments, we adapted a method to
      assess responsiveness of agonists applied to the inside or outside surface of
      canine bronchial segments. A 2 cm "fluid-tight" length of bronchus was cannulated
      and mounted in a perfusion chamber. Auxotonic contraction of the bronchus
      displaced fluid inside the segment up a column and the change in height of fluid
      within the column (afterload) was measured as a change in hydrostatic pressure
      (volumetric). We assessed the optimal conditions for measuring bronchial
      responsiveness to acetylcholine. Neither stretching segments lengthways from 100
      to 140% of resting length, nor altering the transmural pressure from 3 to 21
      cmH2O had a significant effect on the potency of acetylcholine applied to the
      outside surface. Both acetylcholine (n=7) and methacholine (n=4) were
      approximately 10-fold more potent when applied to the outside surface than the
      inside surface of bronchial segments (p<0.0001). Furthermore, mechanical removal
      of the epithelium (n=6) led to a 67-fold increase in potency of acetylcholine
      applied to the inside surface compared with segments with epithelium. The
      advantages that this system has over previously reported methods include: 1)
      agonists can be injected at a low flow rate so as to minimize epithelial stress;
      2) changes in luminal volume are measured under conditions of no flow; 3) after
      load can be varied such that contraction is either practically isotonic or
      auxotonic; and 4) a "barrier effect" of the epithelium of canine bronchial
      segments can be demonstrated. This new adapted method will provide us with the
      means to assess the relationship between in vitro and in vivo responsiveness in
      human bronchi.

PMID- 9657563
TI  - Upper airway cooling reduces upper airway resistance in anaesthetized young
      guinea-pigs.
AB  - In adults, the upper airway (UA) contains a variety of receptors including cold
      receptors, which evoke reflex effects on ventilation and UA dilator muscle
      activity, which may be important in the regulation of UA patency. However, very
      little is known about UA receptors in young animals, and the effects of UA
      cooling on UA dilator muscle activity and resistance have not been studied. A
      constant flow of warm or cool air was applied to the isolated UA in
      anaesthetized, vagotomized young guinea-pigs breathing spontaneously through a
      low-cervical tracheostomy while ventilation, UA resistance and geniohyoid muscle
      electromyographic activity were recorded. Cooling caused an inhibition of
      breathing, a reduction in UA resistance and an excitation of geniohyoid muscle
      activity. Topical anaesthesia of the UA or sealing the nose and cutting the
      superior laryngeal and glossopharyngeal nerves abolished the ventilatory and
      geniohyoid muscle responses but not the fall in UA resistance. It is concluded
      that upper airway cooling reflexly inhibits breathing and excites geniohyoid
      muscle activity. Cooling also reduces upper airway resistance by an effect which
      is not of reflex origin, possibly by reducing upper airway mucosal blood flow.

PMID- 9657564
TI  - Specific immunotherapy downregulates peripheral blood CD4 and CD8 T-lymphocyte
      activation in grass pollen-sensitive asthma.
AB  - Several lines of evidence indicate that specific immunotherapy may act by
      modifying the immune responses of T-lymphocytes to the antigen. To evaluate the
      effect of specific immunotherapy on the activation of T-lymphocytes by cluster of
      differentiation cells (CD4+ and CD8+) in peripheral blood, the expression of two
      surface activation markers, the p55 interleukin-2 receptor (CD25) and human
      leucocyte antigen (HLA)-DR, was studied prospectively on circulating CD4+ and
      CD8+ T-cell subsets in subjects with grass-pollen sensitive asthma before and
      after 1 yr of treatment with specific immunotherapy. Twenty five asthmatic
      patients with pollen sensitivity other than grass, studied out of their pollen
      season, served as the control group. Specific immunotherapy improved clinical
      indices of disease activity including symptom scores and medication use during
      the pollen season of the treatment year. It had a marked effect in reducing the
      expression of the two activation markers, CD25 and HLA-DR, in both CD4+ (p=0.002
      and p=0.005, respectively) and CD8+ (p=0.01 and p=0.01, respectively) T-cell
      subsets, in parallel with a significant decrease in CD23 expression on B-cells
      (p=0.008) and in grass-specific immunoglobulin E levels (p=0.01) in the
      peripheral blood of subjects with grass pollen-sensitive asthma. The decreased T
      lymphocyte activation observed in immunotherapy-treated subjects after the
      treatment year was significant (p=0.05) in comparison with the control group.
      These data add to the view that the efficacy of specific immunotherapy may be
      attributed to the downregulation of T-cell responses.

PMID- 9657565
TI  - Effects of orally inhaled budesonide in seasonal allergic rhinitis.
AB  - It has previously been demonstrated that topical nasal treatment with
      glucocorticosteroids has significant effects on the bronchial airways. Less is
      known about effects on nasal disease by topical bronchial treatment with these
      drugs. The present study examined effects on nasal allergic disease of inhaled
      budesonide (avoiding nasal deposition of the drug). Patients with seasonal
      allergic rhinitis, but without asthma, were thus given inhalations of budesonide
      (600 microg b.i.d.) or placebo. The aim of the design was to allow the study of
      eosinophilic airway disease in a part of the airway other than the directly
      treated locus. Moderate to high birch pollen levels were recorded during the
      study season, and nasal symptoms were significantly increased in both treatment
      groups, although they were milder in patients receiving budesonide than in the
      placebo group (p<0.05). Nasal brush eosinophils and nasal lavage fluid levels of
      eosinophil cationic protein as well as blood eosinophils were increased during
      the season (p<0.05), but these increases were prevented by the inhaled
      budesonide. Nasal lavage fluid levels of alpha2-macroglobulin were particularly
      elevated in the placebo group but did not differ between patients receiving
      placebo and budesonide. Budesonide prevented the seasonal development of
      increased bronchoconstrictor responses to methacholine challenge (p<0.05). In
      conclusion, budesonide reduced the seasonal eosinophilia both in the circulation
      and in the nose along with an attenuation of seasonal nasal symptoms. Hence, at a
      daily dose of 600 microg b.i.d., known to cause no, or minimal, adverse effects,
      inhaled budesonide produces clinically significant anti-inflammatory effects in
      the entire airways, including the nasal mucosa, which is not exposed topically to
      the drug. We suggest that nasal and systemic anti-eosinophil actions are produced
      at commonly employed dose levels of orally inhaled budesonide.

PMID- 9657566
TI  - Detection of immunoglobulins G and A to Aspergillus fumigatus by immunoblot
      analysis for monitoring Aspergillus-induced lung diseases.
AB  - The aim of the study was to investigate whether patients with Aspergillus-induced
      lung disease can be monitored by immunoblot analysis to detect antibodies to
      Aspergillus fumigatus (Af). Immunoblotting was performed by incubating 57
      longitudinally collected sera from 13 patients on nitrocellulose sheets, blotted
      with Af antigen, separated by sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis. Bound antibodies were demonstrated by peroxidase-labelled
      antihuman immunoglobulins (Ig)G and IgA antiserum and diaminobenzidine plus H2O2
      as substrate. The immunoblot patterns were related to the patients' clinical
      status and time. Each patient had a characteristic immunoblot pattern that varied
      with time. There was a relationship between disease activity or clinical response
      and changes in immunoblot antibody patterns: a rise in anti-Af IgG and IgA
      antibodies was seen in sera collected during active disease, compared with before
      active disease, and a significant decline in anti-Af IgG and IgA was demonstrated
      in sera collected during recovery, compared with during active disease. Only in
      the acute stage of allergic bronchopulmonary aspergillosis were IgA antibodies
      against Af antigens of <20,000 Da demonstrated. Immunoblot analysis can be used
      to monitor the disease activity and the responses to treatment of patients with
      Aspergillus-induced lung diseases. Changes in specific immunoglobulin A may be
      more informative than specific immunoglobulin G.

PMID- 9657567
TI  - Role of interleukin-2 in the development and persistence of lymphocytic
      alveolitis in farmer's lung.
AB  - Farmer's lung (FL) is characterized by an intense lymphocytic alveolitis which
      persists after an acute episode with continuous exposure to the offending
      antigens. This study aimed to examine the role of interleukin-2 (IL-2) in the
      development and persistence of this lymphocytic alveolitis. Three groups of dairy
      farmers were studied: acute FL, ex-FL (past history of FL but no clinical
      evidence of active disease) and asymptomatic farmers (no lung disease). IL-2 was
      measured by enzyme immunosorbent assay and T-cell proliferation was evaluated by
      3H-thymidine incorporation. Acute and ex-FL patients had more lymphocytes
      (p<0.01) and higher levels of IL-2 (p<0.05) in their bronchoalveolar lavage (BAL)
      than asymptomatic farmers. BAL T-lymphocytes from acute and ex-FL patients
      released considerable amounts of IL-2 after stimulation with concanavalin A and
      showed dose-dependent proliferative responses to IL-2. IL-2 production was
      decreased after treatment with prednisone. Acute FL patients, but not ex-FL, had
      higher levels of soluble CD25 in their serum than asymptomatics (p=0.009). These
      results suggest that interleukin-2 may play a role in farmer's lung by providing
      a stimulus not only for the accumulation of lymphocytes but also for their
      persistence at the site of hypersensitivity reaction, and that the lung is a
      likely source of this cytokine in vivo.

PMID- 9657568
TI  - Six year longitudinal study of respiratory function in dairy farmers in the Doubs
      province.
AB  - A previous study, carried out in 1986 in France, showed the prevalence of
      respiratory symptoms and of respiratory function impairment to be higher in dairy
      farmers than in a control group of nonexposed subjects living in a rural zone. In
      order to confirm the harmful effect of dairy farming, the two groups were re
      studied 6 yrs later at the same period of the year. One hundred and ninety-four
      (77.6%) farmers and 155 (62%) control subjects were available for re-examination.
      Non-re-evaluated subjects were comparable to re-evaluated subjects for age, sex,
      smoking and respiratory symptoms and function at initial evaluation. Dairy
      farmers consistently had more respiratory symptoms and lower levels of
      respiratory function than did control subjects. In the study populations as a
      whole, the mean annual decline in vital capacity (VC) and forced expiratory
      volume in one second (FEV1) was slightly, but nonsignificantly, higher in farmers
      than in control subjects: in mL x yr(-1) (SD), -43.1 (68.2) versus -37.9 (60.2)
      for VC and -32.8 (56.7) versus -30 (47.2) for FEV1. There was a positive
      interaction between farming and age (i.e. duration of exposure in this cohort) on
      respiratory function decline, and in male subjects aged > or = 45 yrs, dairy
      farming was associated with an accelerated loss in VC (p<0.05) and FEV1 (p<0.05)
      after controlling for age, smoking, height and geographic location in a multiple
      linear regression model. Initial values of respiratory function, age and pack
      years smoked (only for VC) were the other variables found to be significant
      determinants of decline in lung function. In conclusion, this study mainly
      suggests that dairy farming is associated to a very moderate accelerated loss in
      respiratory function that increases with duration of exposure and is significant
      in older male subjects.

PMID- 9657570
TI  - Acid fog and hospital visits for asthma: an epidemiological study.
AB  - The aim of this study was to elucidate the adverse respiratory effects of
      naturally occurring acid fog. In total, 102 adult asthmatic patients (44
      nonatopic and 58 atopic) were studied for a 2 yr period (January 1992 to December
      1993) in Kushiro, a city with only a small industrial area, located in the
      northern-most island in Japan. Fog occurred on 378 out of 731 days, and the
      acidity of the fog ranged from pH 3.32 to 6.91 (mean pH 4.95). The association
      between hospital visits for asthma and meteorological factors or air pollutants
      was investigated. In nonatopic patients, fog, high ozone and water vapour
      pressure, low day-to-day temperature differences, low concentrations of
      atmospheric NO and NO2 contributed significantly (p<0.05) to increasing hospital
      visits. In atopic subjects, fog, high water vapour pressure, low levels of
      atmospheric NO2 and SO2 contributed significantly to hospital visits (p<0.05). In
      Poisson regression analysis the remaining factors of significance (p<0.01) for
      nonatopic asthma were fog and low NO and for atopic asthma were high water vapour
      pressure and low SO2 (p<0.05). A weak but significant correlation was observed
      between the number of hospital visits and the mean pH of the foggy day (r=-0.38,
      p<0.05) in nonatopic asthmatic patients, not in atopic asthma. On foggy days,
      gaseous air pollutant levels were significantly (p<0.01) lower than on fog-free
      days. It was concluded that, naturally occurring acid fog may have a weak
      bronchoconstrictive effect which appears to be more influential in nonatopic
      asthmatic subjects than in atopic subjects.

PMID- 9657569
TI  - Effects of 0.2 ppm ozone on biomarkers of inflammation in bronchoalveolar lavage
      fluid and bronchial mucosa of healthy subjects.
AB  - Short-term exposure to ozone at peak ambient levels induces neutrophil influx and
      impairs lung function in healthy humans. In order to investigate the mechanisms
      contributing to neutrophil recruitment and to examine the role of T-cells in the
      acute inflammatory response, we exposed 12 healthy humans to 0.2 parts per
      million (ppm) of ozone and filtered air on two separate occasions for 2 h with
      intermittent periods of rest and exercise (minute ventilation = 30 L x min(-1)).
      Fibreoptic bronchoscopy was performed 6 h after the end of exposures. Total
      protein, tryptase, histamine, myeloperoxidase, interleukin (IL)-8 and growth
      related oncogene-alpha (Gro-alpha) were measured and total and differential cell
      counts were performed in bronchoalveolar lavage (BAL) fluid. Flow cytometry was
      performed on BAL cells to study total T-cells, T-cell receptors (alphabeta and
      gammadelta), T-cell subsets (CD4+ and CD8+ cells) and activated T-cell subsets
      (CD25+). Using immunohistochemistry, neutrophils, mast cells, total T-cell
      numbers, T-cell subsets, CD25+ T-cells and leukocyte endothelial adhesion
      molecules including P-selectin, E-selectin, intercellular adhesion molecule
      (ICAM)-1 and vascular adhesion molecule (VCAM)-1 were quantified in the bronchial
      biopsies. Paired samples were available from nine subjects. Following ozone
      exposure there was a threefold increase in the proportion of polymorphonuclear
      neutrophils (PMNs) (p=0.07) and epithelial cells (p=0.05) in BAL fluid. This was
      accompanied by increased concentrations of IL-8 (p=0.01), Gro-alpha (p=0.05) and
      total protein (p=0.058). A significant positive correlation was demonstrated
      between the two chemokines and proportion of PMNs in BAL fluid. After ozone
      exposure there was a significant decrease in the CD4/CD8 ratio (p=0.05) and the
      proportion of activated CD4+ (p=0.01) and CD8+ T-cells (p=0.04). However, no
      significant changes were demonstrable in any of the inflammatory markers studied
      in the biopsies. Short-term exposure of healthy humans to 0.2 ppm ozone induced a
      neutrophil influx in peripheral airways at 6 h post exposure, but no apparent
      inflammatory response in proximal airways. This response seems to be mediated at
      least in part by interleukin-8 and growth-related oncogene-alpha.

PMID- 9657571
TI  - Association between PM10 and decrements in peak expiratory flow rates in
      children: reanalysis of data from five panel studies.
AB  - Panel studies have found 1-3% increases in reports of acute respiratory symptoms
      associated with each 10 microg x m(-3) increase in ambient concentrations of
      particles with a 50% cut-off aerodynamic diameter of 10 microm (PM10).
      Statistically significant decrements in population mean peak expiratory flow
      (PEF) have also been observed but their magnitude is only about 0.1% for the same
      exposure. This study evaluated whether this difference is due to the different
      measurement scales used for the expression of the effects of air pollution on PEF
      and respiratory symptoms. The association between the prevalence of large
      decrements in PEF (more than 10% or 20% below the median) and PM10 concentrations
      was analysed using data from five recent panel studies. The effect estimates were
      compared to the effect estimates from original studies based on the population
      mean PEF. The decrement in the population mean PEF for an increase of 10 microg x
      m(-3) of the same-day PM10 concentration was 0.07%, averaged over all panels. A
      significant relative increase of 2.7% (95% confidence interval 1.6-3.8) in the
      prevalence of PEF decrements greater than 10% was associated with the same
      exposure. In conclusion, defining the peak expiratory flow response by the
      prevalence of large decrements provides effect estimates of a comparable
      magnitude to effect estimates for the prevalence of reports of acute lower
      respiratory symptoms.

PMID- 9657572
TI  - Effects of air quality on chronic respiratory symptoms adjusted for allergy among
      preadolescent children.
AB  - The aim of this study was to assess the respiratory effects of outdoor air
      pollution after correcting for allergy and indoor air quality. The respiratory
      health survey targeted 1,129 schoolchildren, 9 yrs of age, attending schools in
      Krakow located in city areas differing in outdoor air pollution levels. Chronic
      phlegm as a unique symptom was related neither to allergy nor to indoor
      variables, but was associated with the outdoor air pollution level (odds ratio
      (OR): 4.2; 95% confidence interval (CI): 1.1-16.9). The same relationship has
      been confirmed for the self-reported local sources of industrial air pollution in
      the area of residence (OR: 4.2; 95% CI: 1.5-11.7). Hay fever appeared to be
      related to outdoor air pollution level (OR: 1.43; 95% CI: 1.1-2.0) and self
      reported heavy traffic (OR: 1.3; 95% CI: 1.0-1.7). In the total sample, wheezing
      was connected exclusively to allergy and parental atopy, while attacks of
      dyspnoea with wheezing and asthma diagnosed by physician only were associated
      with allergy. Since the effect of outdoor pollutants on chronic cough and
      wheezing (odds ratio: 1.85; 95% confidence interval: 1.03-3.33) was only shown to
      be significant in the subsample of children without allergy and parental atopy,
      it may be postulated that either allergy is predisposing to respiratory
      reactions, or outdoor air pollution is coinvolved in an allergization process of
      the preadolescent children. Consequently, allergy should be considered as an
      important confound in epidemiological studies on the respiratory effects of air
      pollution.

PMID- 9657573
TI  - Effect of environmental tobacco smoke on cough in children with a history of
      tonsillectomy or adenoidectomy.
AB  - We examined the possible impact of tonsillectomy or adenoidectomy (T/A) on the
      relationship between environmental tobacco smoke (ETS) exposure and respiratory
      outcomes. This study was conducted in Humboldt, Saskatchewan, in 1993. The target
      population included all residents aged 6-17 yrs. Of the 1,019 eligible subjects,
      892 participated (88%). Estimates of ETS exposure were based on the reported
      smoking habits of the children's household members. We defined current cough as a
      positive response to the question: "Does this child usually have a cough?".
      Information also included morning cough, night cough and a history of T/A. For
      children with no history of T/A, the prevalence of current cough was 8.9%, 12.2%
      and 14.5% for those living in families with 0, 1, and 2+ smokers respectively.
      The corresponding prevalence was 7.0%, 30.2% and 36.8% for children with history
      of T/A. Similar effects of ETS exposure were observed on morning cough and night
      cough. The results did not change significantly when we used various ETS measures
      and controlled for confounding factors. Compared to children living in nonsmoking
      families and without history of T/A, the adjusted odds ratio for children with a
      history of T/A was 7.19 (p<0.001) if they were living in families smoking >20
      cigarettes x day(-1) at home. The corresponding odds ratio was only 1.64 (p=0.11)
      for children without a history of T/A. We concluded that children living in
      smoking family were more likely to cough than those living in nonsmoking families
      and tonsillectomy or adenoidectomy increased the apparent influence of
      environmental tobacco exposure on cough.

PMID- 9657574
TI  - Increasing prevalence of wheeze and asthma in Nottingham primary schoolchildren
      1988-1995.
AB  - The prevalence of asthma in children has increased substantially in many
      countries in recent decades, but it is not clear how much this trend has
      continued into the 1990s. This study aimed to estimate the current prevalence of
      asthma and wheeze in British primary schoolchildren and to determine whether
      there has been any increase in the prevalence of these conditions since 1988. The
      prevalence of self-reported wheeze and asthma was measured by parental
      questionnaire in 22,968 children aged 4-11 yrs attending primary schools in the
      Nottingham area of England in 1995, and these estimates were compared with data
      from a subsample of the same schools in 1988. In 1995, wheezing ever was reported
      in 24.0% of children, wheezing in the past year in 15.1% and diagnosed asthma
      symptomatic in the past year in 8.8%. All measures have increased in prevalence
      since 1988, in absolute terms by 7.7% for wheeze ever, by 2.6% for wheeze in the
      past year and by 2.7% for asthma. The increases were greater in females than
      males, but did not vary with age. In conclusion, the prevalence of asthma has
      continued to rise in British schoolchildren since the late 1980s, particularly in
      females, and across all ages.

PMID- 9657575
TI  - Expression of insulin-like growth factors and their binding proteins by
      bronchoalveolar cells from children with and without interstitial lung disease.
AB  - The involvement of the insulin-like growth factor (IGF) system in lung growth and
      repair following injury is sustained by a number of studies. Based on this
      knowledge, the aim of the present work was to document the expression of the IGFs
      and their binding proteins by alveolar cells obtained by bronchoalveolar lavage
      (BAL). Two groups were investigated: a control group of five children and a group
      of 11 children referred to the department for exploration of interstitial lung
      disease (ILD). Components of the IGF system studied included IGF-I, IGF-II and
      IGF-binding proteins (IGFBP). Expression of these factors was analysed at the
      level of messenger ribonucleic acid (mRNA) (by semi-quantitative reverse
      transcription polymerase chain reaction techniques), and of protein for the
      IGFBPs. In addition, expression of two major cytokines associated with the
      inflammatory process, tumour necrosis factor-alpha (TNF-alpha) and transforming
      growth factor-beta (TGF-beta), was also documented. In children without
      parenchymal disease, the growth factor expressed was IGF-I, in association with
      the presence of mRNA for IGFBP-2 in all cases. In children with ILD, expression
      of IGF-I was observed in nine patients and of IGF-II in three patients, and the
      presence of IGFBP-2 was found in all extracts analysed (mRNA and proteins).
      Evaluation of IGFBP-2 expression indicated an increase in the group of children
      with ILD. Interestingly, a significant association was observed between the
      increase in IGFBP-2 expression and TGF-beta expression. The present data
      emphasize the presence on insulin-like growth factor-binding protein-2 in the BAL
      of all patients, and suggest that this protein may be an important factor of the
      injury/repair processes during the progression of alveolar inflammation.

PMID- 9657576
TI  - Effects of formoterol, salmeterol or oxitropium bromide on airway responses to
      salbutamol in COPD.
AB  - We examined whether a pretreatment with formoterol, oxitropium bromide, or
      salmeterol might modify the dose-response curves to inhaled salbutamol in
      patients with stable and partially reversible chronic obstructive pulmonary
      disease (COPD). Sixteen outpatients with partially reversible, stable COPD
      received 24 microg formoterol, 50 microg salmeterol, 200 microg oxitropium
      bromide, or placebo on four non-consecutive days. Spirometric testing was
      performed immediately before inhalation of treatment and after 2 h. A dose
      response curve to inhaled salbutamol was then constructed using doses of 100,
      100, 200 microg and 400 microg--that is, a total cumulative dose of 800 microg.
      Dose increments were given at 20 min intervals with measurements being made 15
      min after each dose. Formoterol, salmeterol, or oxitropium bromide elicited a
      significant increase in forced expiratory volume in one second (FEV1) compared
      with placebo (mean differences (L) = placebo 0.05; formoterol 0.34; salmeterol
      0.27; oxitropium bromide 0.23). Dose-dependent increases in FEV1 were seen (mean
      values (L) before salbutamol and after a cumulative dose of 100, 200, 400, and
      800 microg = placebo: 1.06, 1.28, 1.35, 1.39, 1.41; formoterol: 1.33, 1.37, 1.41,
      1.44, 1.44; salmeterol: 1.30, 1.33, 1.36, 1.39, 1.42; oxitropium bromide: 1.27,
      1.34, 1.37, 1.41, 1.40). Statistical analysis revealed no significant differences
      in FEV1 and forced vital capacity (FVC) responses to salbutamol after therapy
      with formoterol, salmeterol, or oxitropium bromide compared with placebo. This
      study clearly shows that a pretreatment with a conventional dose of formoterol,
      salmeterol, or oxitropium bromide does not preclude the possibility of inducing a
      further bronchodilation with salbutamol in patients suffering from partially
      reversible chronic obstructive pulmonary disease.

PMID- 9657577
TI  - Deposition and clearance of inhaled 18FDG powder in patients with chronic
      obstructive pulmonary disease.
AB  - As freon is limited in its use as a generator for aerosol inhalation, powder
      particles are used as an alternative for inhalation therapy. The pulmonary
      deposition and clearance of inhaled powder particles was studied by positron
      emission tomography (PET) in ten patients with chronic obstructive pulmonary
      disease (COPD) and in five normal controls. The powder, 5 microm in mean
      diameter, was water soluble and labelled with 2-deoxy-2-[18F]-fluoro-D-glucose
      (18FDG). Powder inhalation was done with single deep inspiration from residual
      volume to total lung capacity. The initial deposition ratio in the right or left
      lung field to total inhaled dose, measured by an anteroposterior rectilinear
      scan, did not differ between normals and COPD patients. Ratios of radioactivity
      detected within the central and peripheral regions (the central to peripheral
      ratio) measured by the PET scan was not significantly different between COPD
      patients (4.8+/-2.6, mean+/-SD) and normals (2.6+/-0.8, mean+/-SD). However, the
      regional powder deposition in peripheral lung fields measured by the PET scan was
      significantly more uneven in COPD patients than in normal patients. The clearance
      rate of 18FDG, defined as the retention ratio of 18FDG activity to the initially
      deposited 18FDG at 60 and 120 min after inhalation, in the trachea, large bronchi
      or peripheral lung fields measured by tomographic scan showed a wider variation
      in COPD patients than in normals. To conclude, inhaled powder tended to be
      deposited more centrally and was distributed more unevenly in the peripheral lung
      in chronic obstructive pulmonary disease patients than in normals. This could be
      a limitation of powder inhalation used for therapy in chronic obstructive
      pulmonary disease patients.

PMID- 9657578
TI  - Noninvasive pressure support ventilation in COPD patients with postextubation
      hypercapnic respiratory insufficiency.
AB  - Patients with chronic obstructive pulmonary disease (COPD) who have been
      intubated and mechanically ventilated may prove difficult to wean. Noninvasive
      ventilation may be used in an attempt to avoid new endotracheal intubation. The
      efficacy of administration of noninvasive pressure support ventilation was
      evaluated in 30 COPD patients with postextubation hypercapnic respiratory
      insufficiency, compared with 30 historically matched control patients who were
      treated conventionally. Patients were included in the study if, within 72 h
      postextubation, they presented with respiratory distress, defined as the
      combination of a respiratory frequency >25 breaths x min(-1), an increase in the
      arterial carbon dioxide tension (Pa,CO2) of at least 20% compared with the value
      measured after extubation, and a pH <7.35. Noninvasive pressure support
      ventilation was effective in correcting gas exchange abnormalities. The use of
      noninvasive ventilation significantly reduced the need for endotracheal
      intubation: 20 of the 30 patients (67%) in the control group required
      endotracheal intubation, compared with only six of the 30 patients (20%) in the
      noninvasive-ventilation group (p<0.001). In-hospital mortality was not
      significantly different between the two groups, but the mean duration of
      ventilatory assistance for the treatment of the postextubation distress, and the
      length of intensive care unit stay related to this event, were both significantly
      shortened by noninvasive ventilation (p<0.01). In conclusion, noninvasive
      ventilation may be used in the management of patients with chronic obstructive
      pulmonary disease and postextubation hypercapnic respiratory insufficiency.

PMID- 9657579
TI  - References values for forced spirometry. Group of the European Community
      Respiratory Health Survey.
AB  - The European Coal and Steel Community (ECSC) prediction equations exemplify a
      significant effort carried out approximately 15 yrs ago to provide uniform
      standards for lung function testing, but this set of equations has not been
      properly validated as yet. The present study evaluates the ECSC reference values
      and four other sets of prediction equations, using spirometric data collected in
      12,900 nonasthmatic subjects (43% lifetime nonsmokers and 36% active smokers)
      aged 20-44 yrs from the European Community Respiratory Health Survey (ECRHS).
      Standardized spirometric measurements were obtained using a common protocol in 34
      centres in 14 countries. For each prediction equation, the prediction deviations
      (i.e. observed minus predicted value) for forced vital capacity (FVC) and forced
      expiratory volume in one second (FEV1) were examined for the whole study
      population and for each centre. For the age range included, the errors about the
      ECSC equations showed the most prominent underestimation of both predicted FVC
      (+355 and +360 mL on average in males and females, respectively) and predicted
      FEV1 (+211 and +200 mL, respectively) among the five studies examined. As
      expected, FVC and FEV1 in active smokers from the ECRHS were significantly lower
      than in lifetime nonsmokers (each p<0.01). We conclude that the present European
      recommendations on lung function reference values should be reconsidered, but
      further data for nonsymptomatic subjects above the age of 44 yrs are needed.

PMID- 9657580
TI  - Respiratory symptoms, lung function and use of health services among unemployed
      young adults in Spain. Spanish Group of the European Community Respiratory Health
      Survey.
AB  - The association of respiratory symptoms, lung function and use of health services
      with employment status was examined in Spain, a country with a high rate of
      unemployment. A population sample comprising 179 unemployed and 1,868 employed
      subjects aged 20-44 yrs in 1993, was randomly selected from a base population of
      about 170,000 people in five urban and rural areas of Spain. Subjects completed a
      questionnaire on respiratory symptoms, sociodemographic and lifestyle factors,
      occupational exposure and use of health services, and performed a forced
      spirometry, a methacholine challenge test and blood tests. Unemployed subjects
      had a higher risk of simple chronic bronchitis (odds ratio=2.06, 95% confidence
      interval 1.30-3.24) and of bronchitis-type symptoms, than those who were
      employed. These risks were, in part, due to the higher prevalence of smoking,
      poorer housing and prior occupational exposures among unemployed than among
      employed people. Smaller differences were found between employed and unemployed
      subjects for asthma-type symptoms, atopia and lung function tests. Use of health
      services among subjects with respiratory symptoms was similar among employed and
      unemployed subjects, except that the latter consistently reported less frequent
      contact with specialized practitioners. Unemployed subjects had a higher risk of
      bronchitis-type symptoms than employed subjects. In Spain's national, free-access
      healthcare system, the differential use of specialized health services by
      employment status is likely to imply differences in the characteristics of the
      healthcare provided.

PMID- 9657581
TI  - Relationship between external resistances, lung function changes and maximal
      exercise capacity.
AB  - In upper airway obstruction (UAO) the relationship between the degree of
      obstruction, exercise limitation and lung function indices is not well
      established. Therefore, we investigated in nine healthy subjects (age 36+/-9 yrs)
      the effects of two added resistances at the mouth (R1 = added resistance with 7.8
      mm diameter; R2 = 5.7 mm) on forced expiratory volume in one second (FEV1), peak
      expiratory flow (PEF), airway resistance (Raw) and maximal breathing capacity
      (measured during 15 s = measured maximum breathing capacity (MBCm); calculated as
      FEV1x37.5 = calculated maximum breathing capacity (MBCc)) on the one hand, and
      maximum exercise capacity (W'max), minute ventilation (V'E) and CO2 elimination
      (V'CO2) on the other. We found that R1 had almost no influence on FEV1 but
      decreased PEF by approximately 35% and increased Raw by almost 300%; it decreased
      W'max by merely approximately 10% while maximal exercise ventilation (V'Emax) was
      only 65% of control and only reached approximately 40% MBCc and approximately 70%
      MBCm; yet V'E and V'CO2 were significantly reduced at high exercise levels
      indicating hypoventilation. With R2, FEV1 was reduced by 25% and PEF by 55%, and
      Raw was increased by 600%; W'max was approximately 60% of control, V'Emax was
      only 35% of control and reached approximately 30% MBCc and approximately 60%
      MBCm, V'E was already reduced at moderate exercise levels. We conclude that: 1)
      an upper airway obstruction of 6 mm diameter (but not of 8 mm) had a marked
      influence on maximum exercise capacity due to hypoventilation; 2) calculated
      maximum breathing capacity markedly overestimated measured maximum breathing
      capacity because the forced expiratory volume in one second is an insensitive
      index of upper airway obstruction and because it does not take inspiratory flow
      limitation into account; and 3) a 10% decrease in maximum exercise capacity was
      linearly related with a 7% decrease in the forced expiratory volume in one second
      and a 150% increase in airway resistance. A 10% decrease in maximal exercise
      ventilation was related to a 8.5% decrease in peak expiratory flow and 9%
      decrease in measured maximum breathing capacity.

PMID- 9657582
TI  - The effect of octreotide on breathing and the ventilatory response to CO2 in
      conscious dogs.
AB  - It has been reported that injection of somatostatin into the brain-stem will lead
      to apnoea in animals. The aim of this study was to determine whether peripheral
      administration of octreotide, an analogue of somatostatin, could influence the
      control of breathing. We measured the tidal volume, respiratory rate and
      ventilatory response to CO2, before and after the intravenous injection of two
      dose levels of octreotide (0.1 mg and 0.5 mg) or saline in four conscious adult
      dogs. Injection of octreotide altered the breathing pattern with a mean decrease
      in the respiratory frequency of 23% (p<0.05) and an increase in the tidal volume
      by 16% (p<0.05), resulting in no net change in ventilation. The normal value of
      the ventilatory response to CO2 ranged between 1.0-3.2 L x min(-1) x mmHg(-1),
      with a minor variance within each dog but a significant difference amongst the
      four dogs (p<0.05). No significant change in the ventilatory response to CO2 was
      observed after octreotide. We conclude that intravenous octreotide alters the
      pattern of breathing but preserves minute ventilation; peripheral administration
      of octreotide does not influence the ventilatory response to CO2.

PMID- 9657583
TI  - Expiratory valves used for home devices: experimental and clinical comparison.
AB  - A bench study followed by a clinical trial were performed to evaluate the
      mechanical characteristics of five (commercially available) expiratory valves
      used for home ventilators, as well as the potential clinical impact of
      differences between these valves. In the in vitro study, expiratory valve
      resistance was evaluated under unvarying conditions, whereas dynamic behaviour
      was evaluated by calculating the imposed expiratory work of breathing during a
      simulated breath generated by a lung model. Differences in resistance and imposed
      expiratory work of up to twofold and 150%, respectively, were found across
      valves. We then conducted a randomized crossover clinical study to compare the
      effects of the least resistive (Bennett) and most resistive expiratory valves
      (Peters) in 10 intubated patients receiving pressure support ventilation. There
      were no significant differences regarding blood gases or respiratory parameters
      except for the oesophageal pressure-time product (PTPoes), which was
      significantly increased by the Peters valve (236+/-113 cmH2O x s x min(-1) versus
      194+/-90 cmH2O x s x min(-1)). An analysis of individual responses found that the
      Peters valve induced substantial increases in intrinsic positive end-expiratory
      pressure (PEEP), PTPoes, and expiratory activity in those patients with the
      greatest ventilatory demand. In conclusion, differences between home expiratory
      valve resistances may have a clinically relevant impact on the respiratory effort
      of patients with a high ventilatory demand.

PMID- 9657584
TI  - Airway response of children with primary ciliary dyskinesia to exercise and beta2
      agonist challenge.
AB  - In primary ciliary dyskinesia (PCD), chest physiotherapy for airway clearance is
      essential. Exercise and inhaled beta2-agonists can produce bronchodilation
      thereby augmenting physiotherapy. However, both can also cause
      bronchoconstriction, and the effects of these stimuli in PCD are not known. In a
      preliminary study, the mean coefficients of variation for forced expiratory
      volume in one second (FEV1), forced vital capacity (FVC) and peak expiratory flow
      rate (PEFR) in children with PCD were determined. They were 5.4%, 4.4% and 8.4%,
      respectively. Twelve children with PCD and 12 normal children performed pulmonary
      functions under resting conditions; during and after a validated treadmill
      exercise test; and before and 15 min after 200 microg of inhaled salbutamol. At
      baseline, FEV1, FVC, forced mid-expiratory flow (FEF25-75%) and PEFR were
      significantly reduced in the PCD group compared with the control group. Exercise
      produced a significant increase in PEFR in the PCD group. There was no
      significant difference between the groups in response to salbutamol. Within the
      PCD group, exercise produced a significantly greater increase in PEFR than beta2
      agonist therapy. In conclusion, in children with primary ciliary dyskinesia there
      is evidence of obstructive pulmonary disease. In these children, exercise is a
      more potent stimulus for bronchodilation than by inhaled beta2-agonists.
      Enhancement of airway clearance may best be achieved by encouraging patients to
      exercise before physiotherapy rather than by inhaling beta2-agonists, but the
      effects of each should be assessed for each individual before instigating
      treatment.

PMID- 9657585
TI  - Magnetic resonance (MR) imaging of the chest: state-of-the-art.
AB  - To date, magnetic resonance (MR) is established as an imaging modality in the
      diagnosis of chest diseases. Because of its excellent distinction of vessels and
      soft tissue, MR can be performed as the primary imaging procedure before computed
      tomography in patients with suspected vascular lesions, mediastinal masses, hilar
      lesions, and pathological changes of the pleura and the chest wall. In these
      cases, MR is able to provide all the necessary diagnostic information. In other
      patients, a limited number of MR images may be helpful in cases of equivocal or
      confusing CT or clinical findings. More detailed information can be obtained,
      using surface coils or special imaging sequences, i.e. high resolution MR images
      of the pleura or angiographic images of mediastinal and pulmonary vasculature.
      From a clinical viewpoint, the most important task for thoracic magnetic
      resonance nowadays is the pretherapeutic evaluation of intrathoracic masses, the
      differential diagnosis of benign versus malignant lesions, and the accurate
      documentation of tumour extent in malignancies including three-dimensional
      display to improve surgical or radiation planning. Future directions in thoracic
      magnetic resonance will be predominantly influenced by postprocessing approaches,
      specialized imaging techniques, and magnetic resonance-guided interventional
      applications.

PMID- 9657586
TI  - Serial sputum cell counts in the management of chronic airflow limitation.
AB  - This case study illustrates the usefulness of serial induced sputum cell counts
      from cytospins to investigate the nature of airway inflammation in a patient
      presumed to have prednisone-dependent asthma for 30 yrs. She had bronchiectasis
      and chronic airflow limitation. Exacerbations of breathlessness were associated
      with an increase in chronic airflow limitation with little or no sputum. Induced
      sputum showed elevated total cell and neutrophil counts at each exacerbation with
      no increase in the proportion of eosinophils. Pathogenic bacteria were cultured
      at each flare-up. The dose of prednisone was reduced progressively and each
      exacerbation was treated with an appropriate antibiotic without increasing the
      dose of prednisone, as was the case previously. The infections were associated
      with bronchiectasis of the right upper lobe which was removed. Examination of the
      specimen confirmed neutrophilic infiltration and did not show the usual airway
      structural changes of asthma. These results provide further evidence of the value
      of sputum cell counts in practice, in this case to prevent overtreatment with
      prednisone in a patient with recurrent deteriorations in airflow which were due
      to recurrent infections.

PMID- 9657587
TI  - Lung abscess complicating chondromas in Carney's syndrome.
AB  - Carney's syndrome consists of a combination of three rare tumours: gastric
      leiomyosarcoma, pulmonary chondroma and catecholamine-secreting paraganglioma. We
      describe a young woman with Carney's syndrome, who developed a lung abscess, due
      to obstruction of a bronchus by a chondroma, 11 yrs after having had a partial
      gastrectomy for a leiomyosarcoma.

PMID- 9657588
TI  - Interstitial lung disease more than 40 years after a 5 year occupational exposure
      to talc.
AB  - A 62 yr old woman was initially diagnosed with sarcoidosis until a thoracoscopic
      biopsy revealed the presence of numerous birefringent particles in fibrotic areas
      of the centrilobular lung zones. These particles were examined by electron
      microscopy and X-ray spectrometry and characterized as impure talc. Further
      inquiry into her occupational history revealed that she had worked from the age
      of 14-18 yrs in a factory making rubber hoses, where she had had an intense
      exposure to talc. There was no evidence of silicosis or asbestosis, and other
      significant causes of interstitial lung disease were excluded. This case
      emphasizes the importance of a thorough occupational history, which may reveal a
      remote and forgotten exposure to a significant cause of interstitial lung
      disease. Although this presentation of talcosis is unusual, this case suggests
      that even a relatively short, but presumably intense exposure to talc more than
      40 yrs previously may be a cause of progressive lung fibrosis.

PMID- 9657589
TI  - Guidelines for mineral fibre analyses in biological samples: report of the ERS
      Working Group. European Respiratory Society.
AB  - Microscopic techniques for analysing asbestos fibres in lung tissue and
      bronchoalveolar lavage have provided major information in the understanding of
      asbestos-related diseases. These analyses are increasingly applied for clinical
      work and medicolegal problems. Differences in sampling, preparation and counting
      techniques, definitions of reference populations and expression of results have
      caused major difficulties in comparing results from different laboratories.
      Therefore it appeared necessary to set a goal to harmonize these analyses between
      the European laboratories active in this field. This article summarizes the work
      of a European Respiratory Society working group with participation from nine
      European laboratories. The five main issues touched upon are: 1) definitions of
      control populations and reference levels; 2) sampling, preparation and analytical
      techniques; 3) asbestos fibres in lung tissues in different pathologies; 4)
      asbestos bodies in lung tissue, bronchoalveolar lavage and sputum; and 5) basis
      for the interpretation of fibres and asbestos bodies in biological samples. These
      guidelines indicate the crucial importance of several factors for the
      interpretation of the results; namely, adequate sampling, comparable analytical
      procedures and expression of the results, the use of well-defined reference
      populations, and a comprehensive understanding of the factors affecting the fibre
      retention and the dose-responses associated with the different asbestos-related
      diseases.

PMID- 9657590
TI  - Asbestos, ergot drugs and the pleura.

PMID- 9657591
TI  - Macrolide antibiotics in diffuse panbronchiolitis and in cystic fibrosis.

PMID- 9657593
TI  - Analysis of blood chemistry and hearing levels in a sample of older persons.
AB  - OBJECTIVE: As part of an ongoing study of presbyacusis, the relationship between
      blood chemistry levels and hearing levels was investigated. Previous reports
      often used small sets of blood chemistry measures, and results were inconclusive.
      This experiment examined hearing levels and 27 measures of blood chemistry using
      various univariate and multivariate statistical procedures. DESIGN: Blood from 89
      female and 128 male human subjects was collected. Subjects' ages ranged from 60
      to 82 yr, and hearing levels ranged from normal to moderate/severe. Subjects with
      a history of middle ear disease were excluded. Electrolyte panel (Na, K, Cl, CO2,
      Ca, urea nitrogen, glucose, creatinine, and Mg), hematology panel (WBC, RBC, Hgb,
      hematocrit, platelet, etc.), serum lipids (total cholesterol, low-density
      lipoprotein [LDL], and high-density lipoprotein [HDL]), immunoglobulins (IgG,
      IgA, IgM, and IgE), and thyroxine were analyzed using univariate and multivariate
      statistical procedures. RESULTS: Blood chemistry levels of most subjects were
      within normal ranges as defined by our laboratory. Correlation between blood
      chemistry measures and pure-tone averages (PTAs) ranged from minimal to low.
      Results of factor analysis, discriminant analysis, and canonical analysis showed
      that combining blood chemistry measures from the same panel still could not
      predict PTA effectively. One exception to this was a gender-specific effect of
      cholesterol. Hearing levels of women with high LDL/HDL ratios were 5 dB better
      than those of women with low LDL/HDL ratios. The comparable difference in men was
      only 1 dB. CONCLUSION: Results suggest that blood chemistry measures that are
      primarily within the normal range have very little value in predicting pure-tone
      thresholds in older subjects.

PMID- 9657592
TI  - Transient deafness due to temperature-sensitive auditory neuropathy.
AB  - OBJECTIVE: To define mechanisms accounting for transient deafness in three
      children (two siblings, ages 3 and 6, and an unrelated child, age 15) when they
      become febrile. DESIGN: Audiometric tests (pure-tone audiometry, speech and
      sentence comprehension), tympanometry, middle ear muscle reflex thresholds,
      otoacoustic emissions (OAEs), and electrophysiological methods (auditory brain
      stem responses [ABRs], sensory evoked potentials, peripheral nerve conduction
      velocities) were used to test the children when they were afebrile and febrile.
      RESULTS: ABRs, when afebrile, were abnormal with a profound delay of the IV-V and
      absence of waves I-III. The ABR in one of the children, tested when febrile,
      showed no ABR components. Measures of cochlear receptor function using OAEs were
      normal in both febrile and afebrile states. Cochlear microphonic potentials were
      present in the three children, and a summating potential was likely present in
      two. When afebrile, there was a mild threshold elevation for all frequencies in
      the 15-yr-old and a mild elevation of thresholds for just low frequencies in the
      two siblings. Speech comprehension in quiet was normal but impaired in noise. One
      of the siblings tested when febrile had a profound elevation (>80 dB) of pure
      tone thresholds and speech comprehension was absent. Acoustic reflexes subserving
      middle ear muscles and olivocochlear bundle were absent when febrile and when
      afebrile. No other peripheral or cranial nerve abnormalities were found in any of
      the children. Sensory nerve action potentials from median nerve in one of the
      children showed no abnormalities on warming of the hand to 39 degrees C.
      CONCLUSION: These children have an auditory neuropathy manifested by a disorder
      of auditory nerve function in the presence of normal cochlear outer hair cell
      functions. They develop a conduction block of the auditory nerves when their core
      body temperature rises due, most likely, to a demyelinating disorder of the
      auditory nerve. The auditory neuropathy in the two affected siblings is likely to
      be inherited as a recessive disorder.

PMID- 9657594
TI  - Psychological change over 54 months of cochlear implant use.
AB  - OBJECTIVE: To determine the long-term psychological outcome of postlingually
      deafened adults who received multichannel cochlear implants and to relate the
      psychological outcome to audiological outcome. DESIGN: Thirty-seven recipients of
      multichannel cochlear implants who participated in a prospective clinical trial
      completed psychological assessments before implantation and at regularly
      scheduled follow-ups through 54 mo of implant use. Standardized measures of
      affect, social function, and personality were used, and scores on these measures
      were correlated with asymptotic scores on several audiological measures. RESULTS:
      Evidence of significant improvement on measures of loneliness, social anxiety,
      and distress were obtained within a year after implantation and throughout the
      duration of the follow-up period. For measures of assertiveness and marital
      satisfaction, improvement was apparent only after long-term implant use. Although
      favorable changes on the Minnesota Multiphasic Personality Inventory (MMPI)
      Depression Scale were evidenced only in the initial follow-up period,
      improvements on the MMPI Paranoia and Social Introversion Scales persisted
      throughout the 54 mo follow-up. CONCLUSION: Multichannel cochlear implant use is
      associated with long-term psychological benefit. Correlations between
      audiological outcome and psychological outcome, however, suggested that the
      relation between audiological benefit and psychological benefit is not simple.

PMID- 9657595
TI  - Experiments with classroom FM amplification.
AB  - OBJECTIVES: 1) To quantify the benefits of FM amplification for persons with
      severe and profound hearing loss; 2) to compare a body-worn and a behind-the-ear
      FM system; 3) to measure the effects of reducing FM microphone sensitivity
      relative to hearing aid sensitivity. DESIGN: Recognition of phonemes in lists of
      consonant-vowel-consonant words was measured in 13 teenage students with severe
      and profound hearing loss. Presentation was by live voice at 10 feet from the
      listeners and 12 inches from the FM microphone/transmitter. Students listened: a)
      via a body-worn and a behind-the-ear system; b) with the FM
      microphone/transmitter on and off; c) in noise and in quiet. Systems were
      adjusted so that sinusoidal inputs of 65 dB SPL gave equal gains via the FM and
      hearing aid microphones. In a follow-up study, the gain via the FM microphone was
      reduced so that a sinusoidal input of 65 dB SPL into the hearing aid microphone
      produced the same output as a sinusoidal input of 80 dB into the FM microphone
      (as recommended in American Speech-Language-Hearing Association, 1994). RESULTS:
      1) Addition of the FM microphone signal to that available from the hearing aid
      microphone was equivalent, on average, to doubling the number of independent
      channels of information available to the listeners. 2) FM benefit was present in
      both quiet and noise but was somewhat greater in noise. 3) Contrary to
      prediction, however, noise interfered with phoneme recognition even under the
      aid+FM condition. 4) Differences between the body-worn and behind-the-ear systems
      were small, but there was a measurable advantage for the body-worn system under
      the aid+FM condition. 5) Reducing FM microphone sensitivity by 15 dB virtually
      eliminated the FM benefit. 6) Forty-four percent of the variance in phoneme
      recognition (averaged across listening conditions) could be explained by better
      ear, three-frequency average pure-tone threshold. 7) Vowels were recognized more
      easily than consonants, and initial consonants were recognized more easily than
      final consonants, but the FM benefit was present for all three phonemes.
      CONCLUSIONS: The findings confirm the value of FM amplification for persons with
      severe and profound hearing loss, in both quiet and noise. The negative effects
      of noise were not completely eliminated, however, under the aid+FM condition.
      This finding can be attributed to a reduction of gain in the FM channel, when
      speech input was used, because of compression limiting in the microphone
      transmitter. The superiority of the body-worn system under the aid+FM condition
      suggests a need for higher saturation sound pressure level in the behind-the-ear
      system when used with persons having severe and profound hearing loss. The
      findings do not support use of an "equal output" criterion for adjusting relative
      gains via the FM and hearing aid microphones--at least for persons with very
      severe and profound hearing loss operating under the conditions tested in this
      study.

PMID- 9657596
TI  - The effects of broadband noise masking on cortical event-related potentials to
      speech sounds /ba/ and /da/.
AB  - OBJECTIVE: To systematically investigate in normal-hearing listeners the effects
      of decreased audibility produced by broadband noise masking on the cortical event
      related potentials (ERPs) N1, N2, and P3 to the speech sounds /ba/ and /da/.
      DESIGN: Ten normal-hearing adult listeners actively (button-press response)
      discriminated the speech sounds /ba/ and /da/ presented in quiet (no masking) or
      with broadband masking noise (BBN), using an ERP oddball paradigm. The BBN was
      presented at 50, 60, and 70 dB SPL when speech sounds were presented at 65 dB ppe
      SPL and at 60, 70 and, 80 dB SPL when speech sounds were presented at 80 dB ppe
      SPL. RESULTS: On average, the 50, 60, 70, and 80 dB SPL BBN maskers produced
      behavioral threshold elevations of 18, 25, 35, and 48 dB (average for 250 to 4000
      Hz), respectively. The BBN maskers produced significant decreases (relative to
      quiet condition) in ERP amplitudes and behavioral discriminability. These
      decreases did not occur, however, until the noise masker intensity (in dB SPL)
      was equal to or greater than the speech stimulus intensity (in dB ppe SPL), that
      is, until speech to noise ratios (SNRs) were < or = 0 dB. N1 remained present
      even after N2, P3, and behavioral discriminability were absent. In contrast to
      amplitudes, ERP and behavioral latencies showed significant decreases at higher
      (better) SNRs. Significant latency increases occurred when the noise maskers were
      within 10 to 20 dB of the stimuli (i.e., SNR < or = 20 dB). The effects of
      masking were greater for responses to /da/ compared with /ba/. Latency increases
      occurred with less masking for N1 than for P3 or behavioral reaction time, with
      N2 falling in between. CONCLUSIONS: These results indicate that decreased
      audibility as a result of masking affects the various ERP peaks in a differential
      manner and that latencies are more sensitive indicators of these masking effects
      than are amplitudes.

PMID- 9657597
TI  - Binaural masking level difference in human binaural interaction components.
AB  - OBJECTIVE: The purpose of this study was to compare the effects of monaural and
      binaural broadband masking noise on binaural interaction components (BICs) of the
      human auditory brain stem evoked potentials (ABEPs). DESIGN: The BICs of the
      human ABEPs were studied by subtracting the potentials to binaural clicks from
      the algebraic sum of monaurally evoked potentials to clicks alone or to clicks
      with ipsilateral monaural or binaural broadband masking noise. Alternating
      polarity, 11/sec clicks were presented at 65 dB nHL, and noise was presented at
      45 dB nHL. Analysis included peak-to-prestimulus baseline amplitudes and
      latencies of BICs' peaks and troughs from the vertex-mastoid (A) and vertex-neck
      (Z) channels. In addition, 3-channel Lissajous' trajectory (3-CLT) analysis,
      estimating the single, centrally located dipole equivalent of surface activity,
      was performed on data recorded from three orthogonally positioned electrode
      pairs. 3-CLT measures included apex latency, amplitude, and orientation, as well
      as planar segment duration, size, shape, and orientation. RESULTS: All BICs 3
      CLTs included five main components (labeled BdI, BdII, BdIII, BeI, and BeII). In
      general, apex latencies were longer with masking noise. However, BdII and BeI
      apex latencies were shorter with binaural than with ipsilateral monaural masking
      noise. Apex amplitude and planar segment size of component BeI, as well as P1
      peak amplitude in BICs of the Z-channel records, were larger with binaural than
      with monaural noise. No significant difference between the monaural and binaural
      noise conditions was found in durations, shapes, and orientations of planar
      segments of BICs 3-CLT, nor in peak latency of BICs in the A- and Z-channel
      records. CONCLUSIONS: We suggest that these effects on the latency and amplitude
      of BICs reflect binaural processing in the human brain stem. In particular, the
      larger amplitudes and shorter latencies of P1 and BeI with binaural than with
      ipsilateral monaural masking may be associated with the psychophysical effect of
      binaural masking level difference.

PMID- 9657598
TI  - Clinical applicability of the sweep frequency measuring apparatus for diagnosis
      of middle ear diseases.
AB  - OBJECTIVE: To develop a measuring apparatus that has the ability to sweep both
      frequency and external auditory meatus static pressure and can display
      measurement results in a three-dimensional expression. To measure the middle ear
      dynamic characteristics of normal-hearing subjects and of patients with this
      apparatus. DESIGN: Investigate 275 ears of 153 normal-hearing subjects and 72
      ears with middle ear diseases. RESULTS: The measurement results show fairly
      distinctive patterns depending on the middle ear conditions, i.e., normal,
      ossicular chain separation, ossicular chain fixation, secretory otitis media,
      tympanic membrane perforation, and tympanic membrane atelectasis. The evaluation
      of patients with ossicular diseases revealed that the rate of correct diagnosis
      of ossicular chain separation is 84% and that of ossicular chain fixation is 74%.
      These diagnoses were confirmed by surgery. CONCLUSION: Displaying the measurement
      results in a three-dimensional expression is helpful to make correct diagnosis in
      clinical practice. It is especially easy to make a distinction between the
      ossicular chain separation and ossicular chain fixation. Therefore, it is
      concluded that this apparatus has a high degree of clinical applicability to the
      diagnosis of these diseases.

PMID- 9657599
TI  - A deterministic model for the economic evaluation of broiler production systems.
AB  - A deterministic model for the economic evaluation of broiler production and the
      derivation of economic values in broiler breeding was developed and tested. The
      model distinguishes four production stages: multiplier breeder, hatchery,
      commercial grower, and processor. The processor is included to determine
      relationships for the price per kilogram of live weight and the quality of the
      carcass, either on a "whole sale" or "further processed" base. Quantity of
      product output for the system is fixed by a predetermined amount of kilogram
      carcass of final product broilers finished by the commercial grower.
      Profitability of production and cost prices per unit product for subsequent
      stages can be calculated. Exogenous parameters are easily changeable in order to
      calculate profitability and cost prices for different production levels or
      production circumstances. Economic values can be derived considering influences
      of changes in genetic merit for performance traits on profitability or cost
      price, for integrated and nonintegrated production systems. By changing exogenous
      parameters, the model can also be used to analyze profitability or derive
      economic values for other meat-type poultry, such as turkey.

PMID- 9657600
TI  - Economic values in broiler breeding.
AB  - The objectives of this study were to derive economic values in broiler breeding
      and to determine their relationship with production circumstances. Economic
      values were derived using a deterministic economic model based on profit
      equations with a fixed amount of broiler meat output of the production system.
      Nonintegrated and the integrated broiler production systems were studied. The
      difference between these originates from different definitions of cost components
      and scaling aspects. For each stage of an nonintegrated system, the model
      calculated the profit margin; for an integrated system, (total) cost prices per
      unit of product at each stage were calculated. The Dutch broiler performance data
      and prices were input into the model as the representative situation. For all
      traits, in the nonintegrated system, economic values were derived, expressed as
      Dutch guilders (Dfl) per unit of product, where the unit of product depends on
      the stage of the production system and equals an egg for the multiplier breeder,
      a day-old chick for the hatchery, and a marketable broiler for the commercial
      grower and processor. Resulting levels of economic values were illustrated by
      showing underlying cost or profit changes in the production system. For the
      integrated system, economic values were expressed as Dfl x marketable broiler(-1)
      x unit(-1). Economic values of traits in the integrated system were also derived
      for situations where technical parameters or prices of productive factors were
      changed (20% increase or decrease). A general conclusion from these sensitivity
      analyses is that the economic values are sensitive to production levels, product
      prices and feed prices; there are both linear and nonlinear relationships between
      economic values and production circumstances.

PMID- 9657601
TI  - Heterogeneity of staphylococci and other bacteria isolated from six-week-old
      broiler chickens.
AB  - In broiler operations, various health problems develop during the final 2 wk of
      the growing period, resulting in increased mortality and condemnation losses. At
      this stage, sickly birds were found to be systemically infected by various
      bacteria regardless of varied clinical signs, and the purpose of this study was
      to carry out thorough microbiological investigations on this problem. Thirty-one
      6-wk-old broilers showing signs of illness were obtained from three farms, and
      bacterial isolations were carried out from the blood, liver, and hock joint.
      Bacteria were isolated from 87, 90, and 71% of the blood, liver, and hock joint
      samples, respectively. Mean bacterial counts in log10 of the blood (per
      milliliter) and liver (per gram) were 2.15 and 2.93, respectively. Among 132
      bacterial isolates, major species were Staphylococcus (60%), Corynebacterium
      (18%), Escherichia coli (5%), and Stomatococcus (4%). Among 79 Staphylococcus
      isolates, 77 were coagulase-negative. Major species of staphylococci were S.
      lentus (19%), S. simulans (18%), S. cohnii (13%), S. gallinarum (10%), and S.
      captis (7%). In addition, six species of gram-positive and five species of gram
      negative organisms were isolated. Thus, the apparent systemic infections were not
      caused by predominant pathogenic bacterial species, and adequately described as
      mixed infections. There were some significant relationships between isolated
      bacterial species and sampling sites, suggesting that certain organisms were
      abundant in the environment of a particular poultry house. These results indicate
      that systemic infections in market age broilers are caused by mixed bacterial
      species and suggest that they are caused by suppressed host antibacterial systems
      rather than pathogenic factors of microorganisms.

PMID- 9657602
TI  - Intervention decision model to prevent spiking mortality of turkeys.
AB  - Based on the daily records on turkeys' mortalities for the series of flocks
      placed on different farms in a relatively compact geographical area for the
      period of approximately 2 yr and other relevant explanatory variables, the goal
      of the research was to design a decision model to determine whether or not to use
      the fluorquinolone antibiotic, sarafloxacin, to prevent spiking mortality of
      turkeys. The core of the designed decision model is the forecasting model that
      attempts to ex-ante predict the cumulative flock mortality for the period between
      8 and 28 d of age. Forecasts were generated with the parameters of the linear
      regression model where continuous values of daily mortalities served as a
      dependent variable. The decision variable is a binary (yes/no) choice variable,
      where "yes" means "go ahead with treatment" and "no" means "do nothing". If the
      predicted cumulative mortality for the period between 8 and 28 d of age exceeds
      9% of the total initial placement, the model generates a "yes" signal. If the
      predicted cumulative mortality for the same period is below 9% of the total
      initial placement, the model generates a "no" signal. The results indicate a
      reasonable accuracy of the prediction model where the number of correct
      prediction increases and the number of incorrect predictions falls very fast as
      the forecasting window shortens. The intervention decision model could help
      veterinarians in making decisions on whether or not to treat the suspect flocks.

PMID- 9657603
TI  - Humoral immune response impairment following excess vitamin E nutrition in the
      chick and turkey.
AB  - The effect of high dietary intakes of vitamin E on antibody production was
      investigated in chicks and turkeys. Chicks were fed four diets with 0, 10, 30,
      and 150 mg/kg added vitamin E and turkeys were fed three diets with 0, 50, and
      150 mg/kg added vitamin E. Antibodies produced in response to naturally occurring
      Escherichia coli and to Newcastle disease virus and turkey pox vaccines were
      determined. In chicks, antibody production in response to E. coli and Newcastle
      disease was affected by vitamin E nutrition: significantly higher responses were
      measured in chicks that received 0 and 10 mg/kg added vitamin E, whereas in
      chicks receiving 30 and 150 mg/kg, antibody production was significantly lower.
      In turkeys, concentrations of circulating antibodies to Newcastle disease virus
      and to turkey pox were also influenced by dietary vitamin E: antibody titers to
      Newcastle disease and turkey pox vaccines were highest in groups receiving 0
      mg/kg added vitamin E, whereas titer in groups receiving 150 mg/kg were
      significantly lower. Responses of groups receiving 50 mg/kg added vitamin E were
      slightly lower than groups receiving 0 mg/kg, though not significantly so in most
      cases. These results indicate that humoral immune responses are directly effected
      by vitamin E, and that excessive vitamin E intake has a detrimental effect on
      antibody production in chickens and turkeys.

PMID- 9657605
TI  - Lymphokine-augmented activation of avian heterophils.
AB  - Heterophils are important mediators of innate resistance in poultry, especially
      in young birds that have not yet developed an acquired immune response. Invasion
      of the intestinal mucosa by Salmonella spp. initiates the recruitment of large
      numbers of heterophils to the lamina propria. Thus, the heterophilic response can
      control, but not eliminate, bacterial numbers in the bird until development of
      acquired immunity. Unfortunately, chicks and turkey poults are highly susceptible
      to Salmonella infections during the first 4 d posthatch due to the functional
      immaturity of both the innate and acquired immune systems. We have previously
      shown that the administration of Salmonella enteritidis (SE)-immune lymphokines
      (ILK) into either 18-d-old developing embryos or day-of-hatch chicks and poults
      conferred increased resistance to SE organ invasion. In this review, we present
      evidence that the protection induced by ILK is mediated by vigorous recruitment
      and activation of heterophils. These activated heterophils migrate rapidly to the
      site of bacterial invasion where they phagocytize and kill the SE. Specifically,
      in vitro studies demonstrate an enhancement of functional activities of the
      heterophils including chemotaxis, adherence, phagocytosis, and bacterial killing.
      In addition, during the activation process, membrane expression of adhesion
      molecules rapidly changes from L-selectins to beta2 integrins (CB11b/CD18) on the
      cells that become activated. These results further demonstrate the validity of
      preventive activation in poultry to induce the migration of large numbers of
      activated phagocytic cells to the site of infection by a pathogenic organism.
      Importantly, this immunopotentiation of the inflammatory response by ILK, as
      described here, induces the functional maturation of heterophils during the first
      4 d posthatch.

PMID- 9657606
TI  - Avian heterophils in inflammation and disease resistance.
AB  - Heterophils are the predominate granulated leukocyte in the acute inflammatory
      response in gallinaceous birds. Heterophils are highly phagocytic and are capable
      of a broad spectrum of antimicrobial activity. They accumulate in inflamed
      tissue, causing tissue damage and forming heterophil granulomas that are
      morphologically similar to inflammatory lesions in reptiles. The avian heterophil
      lacks myeloperoxidase and depends primarily on nonoxidative mechanisms for
      antimicrobial activity. The beta-defensins found in heterophil granules can kill
      a wide variety of bacterial pathogens and are a major component of the heterophil
      antimicrobial arsenal. Heterophils form the first line of cellular defense
      against invading microbial pathogens in the lungs and air sacs where resident
      macrophages are lacking.

PMID- 9657607
TI  - Role of macrophages in avian health and disease.

PMID- 9657608
TI  - Avian macrophages: regulators of local and systemic immune responses.
AB  - Macrophages are key regulatory cells of the immune system involved in initiating
      and directing the innate and specific immune responses, the systemic acute phase
      response, tissue repair, and tissue remodeling. In the early stages of a
      challenge from invading microorganisms or from tissue injury, macrophages defend
      local and systemic homeostasis by initiating a complex series of cellular,
      biochemical, and behavioral events. These pathophysiological adjustments are
      mediated by an extensive variety of communication molecules, including:
      cytokines, cytokine inhibitors, endocrine hormones, eicosanoids,
      neurotransmitters, and reactive oxygen intermediates. The cytokines produced by
      macrophages (monokines) are not well characterized relative to their mammalian
      counterparts, but a variety of chemokine, pro-inflammatory, and colony
      stimulating factor activities have been described. Although the sequence
      homology, and thus species cross-reactivity, between avian and mammalian
      cytokines is typically low, the functional characteristics appear to be generally
      similar. The pro-inflammatory cytokines are important initiators and regulators
      of the local immune response. They are also released in sufficient quantities
      during some infections to coordinate a systemic acute phase response that impacts
      the growth, reproduction, and well-being of poultry. An understanding of the
      mechanisms and molecules used by macrophages to regulate immune and inflammatory
      responses may permit the development of products, diets, or husbandry techniques
      to modulate immunity for the enhancement of the productivity of poultry.

PMID- 9657609
TI  - Avian macrophage metabolism.
AB  - This review considers the role of avian macrophages as a source of immune
      effector and immunoregulatory metabolites. Although considerable attention has
      been given to the importance of leukocytic cytokines, particularly the monokines
      such as interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-alpha
      (TNF-alpha), and transforming growth factor-beta (TGF-beta), metabolites produced
      by macrophages appear to be of equal importance in determining the progression of
      immune responses. The three metabolite categories that have received the greatest
      attention are the reactive oxygen species (ROS), the reactive nitrogen
      intermediates (RNI), and the eicosanoids. Additionally, the xenobiotic
      metabolites produced via cytochrome P450 activity mediate some immune
      environmental interactions. Each of these four metabolite categories is subject
      to different requirements for metabolite production, and each has distinct
      effector functions. An understanding of macrophage metabolite regulation could
      allow improvements in avian health management and production via the effective
      control of metabolite production. The present review considers prior and recent
      information on the production of the metabolites by avian macrophages.
      Additionally, the potential ramifications of metabolite production and regulation
      are discussed.

PMID- 9657610
TI  - Threonine requirements of laying hens.
AB  - In order to determine the Thr requirement of laying hens, two experiments were
      conducted using laying performance and plasma Thr concentration as parameters. At
      29 and 39 wk of age, 100 and 600 laying hens in Experiments 1 and 2,
      respectively, with average BW and high egg production rate, were randomized,
      housed in individual cages, and given free access to water and experimental diets
      with five graded levels of Thr: 0.31, 0.39, 0.46, 0.54, and 0.61% for 21 d in
      Experiment 1 and diets with 0.31, 0.36, 0.41, 0.46 and 0.51% Thr for 58 d in
      Experiment 2. On the last day of the experiment, blood samples were taken for
      determination of plasma amino acid concentration. Feed intake and daily egg mass
      increased and then decreased linearly as dietary Thr increased. Plasma Thr
      increased slowly, then sharply with increasing dietary Thr levels. Using the
      broken-line model, the Thr requirements were estimated to be 0.425, 0.428, and
      0.430% or 453, 456, and 458 mg/hen per d in Experiment 1 and 0.395, 0.404, and
      0.400%, or 457, 467, and 462 mg/hen per d, in Experiment 2, for egg mass, feed
      efficiency, and plasma Thr concentration, respectively. These results indicate
      that the Thr requirements expressed as milligrams per hen per day as determined
      by plasma Thr concentration agree with those of laying performance.

PMID- 9657611
TI  - Bioavailability of the digestible lysine and total sulfur amino acids in meat and
      bone meals varying in protein quality.
AB  - Experiments were conducted to determine whether the digestible Lys, Met, and TSAA
      in a high and low quality meat and bone meal (MBM) were totally bioavailable for
      protein synthesis in chicks. True digestibility of amino acids (AA) in the two
      MBM was determined by the precision-fed cecectomized rooster assay.
      Bioavailability of the digestible AA was then assessed in three slope-ratio chick
      growth assays using Lys-, Met-, or TSAA-deficient crystalline AA basal diets that
      were supplemented with varying levels of the test AA, high or low quality MBM, or
      AA mixtures simulating the mean digestible AA composition of the high and low
      quality MBM. Response parameters were weight gain, feed efficiency, body N gain,
      and body Lys gain in the Lys assay and weight gain and feed efficiency in the Met
      and TSAA assays. Bioavailability values for the digestible Lys, Met, and TSAA in
      the MBM and AA mixtures simulating MBM varied depending on response parameter,
      with values based on feed efficiency generally being highest. No consistent
      differences in bioavailability of the digestible AA were observed between the two
      MBM when all AA were considered; however, the bioavailability of the digestible
      Lys in the low quality MBM was lower than that in the high quality MBM for two of
      four performance criteria. When considering all response parameters and the AA
      mixture results, bioavailability of the digestible Lys and Met in the two MBM was
      generally 90% or greater, whereas bioavailability of the digestible TSAA was only
      80% or less. The results of this study indicated that essentially all of the
      digestible Lys and Met in MBM were bioavailable for protein synthesis and
      metabolism but suggested that a significant amount of the TSAA, particularly Cys,
      was not bioavailable.

PMID- 9657612
TI  - Dietary formulation with meat and bone meal on a total versus a digestible or
      bioavailable amino acid basis.
AB  - The digestibility and bioavailability of amino acids (AA) in meat and bone meals
      (MBM) may vary greatly due to different processing conditions. In the present
      study, two experiments were conducted to evaluate formulation of diets containing
      high or low quality MBM on a total AA basis vs a digestible or bioavailable AA
      basis compared to a corn-soybean meal control diet. Lysine, methionine, and
      cystine digestibilities (precision-fed cecectomized rooster assay) were 92, 91,
      and 71%, respectively, for high quality MBM and were 71, 83, and 31%,
      respectively, for the low quality MBM. Bioavailability values (slope-ratio chick
      growth assay) for TSAA in the two MBM were approximately 15 percentage units
      lower than the digestibility values. Male crossbred chicks were fed a 20% CP corn
      SBM diet or corn-SBM diets containing 10 or 20% high or low quality MBM that were
      formulated to be equal in total, digestible, or bioavailable AA to the corn-SBM
      diet. All diets contained 3,200 kcal of TMEn/kg, 1.4% Ca, and 0.7% nonphytate P
      and were fed to chicks from 8 to 22 d posthatching. Growth performance of chicks
      fed 10 or 20% high or low quality MBM on a total AA basis was lower (P < 0.05)
      than that of chicks fed the corn-SBM diet. Growth of chicks fed 10% low quality
      MBM or 10 or 20% high quality MBM on a digestible or bioavailable basis was
      equivalent to that of chicks fed the corn-SBM diet; however, dietary inclusion of
      20% low quality MBM depressed growth (P < 0.05) even on a digestible or
      bioavailable AA basis. Further supplementation of the latter diet with additional
      AA yielded growth that was similar to the corn-SBM control diet. The results
      indicated that formulation of diets containing MBM on a digestible or
      bioavailable AA basis is superior to formulation on a total AA basis. However,
      feeding high levels of a low quality MBM may require additional AA
      supplementation to obtain maximum chick growth.

PMID- 9657613
TI  - Availability of amino acids in high-oil corn.
AB  - True digestibility of amino acids, bioavailability of Lys, and TMEn in three
      types of high-oil corn (HOC) and one conventional corn (CC) were determined. The
      CC, HOC1, HOC2, and HOC3 contained 4.3, 5.9, 6.6, and 9.5% ether extract,
      respectively, on a DM basis. True digestibility of amino acids was determined
      using the precision-fed cecectomized rooster assay in which each corn sample was
      tube-fed (30 g) to nine roosters and excreta were collected for 48 h. True
      digestibility of most amino acids in HOC2 and HOC3 were significantly higher (P <
      or = 0.05) than those in CC and HOC1. Mean digestibility of 15 amino acids in
      HOC2 and HOC3 was 91% compared to 80% for CC and HOC1. The TMEn values
      (kilocalories per gram DM) of CC, HOC1, HOC2, and HOC3 were 3.883, 4.024, 4.038,
      and 4.140, respectively. Lysine bioavailability was assessed using a slope-ratio
      chick growth assay in which a Lys-deficient crystalline amino acid diet was
      supplemented with 0, 0.1, or 0.2% L-Lys from L-Lys x HC1 to provide a standard
      curve. Six additional dietary treatments consisted of supplementing the basal
      diet with 28 or 56% of CC, HOC2, or HOC3. The nine diets were fed to four
      replicate groups of six chicks from 8 to 18 d posthatching. Lysine
      bioavailability was calculated using multiple regression slope-ratio methodology
      where Y was weight gain and X was intake of Lys from the L-Lys x HC1 or a corn.
      Supplementation of the basal diet with L-Lys x HC1, CC, HOC2, or HOC3 yielded
      linear (P < or = 0.001) growth responses. Bioavailability values (percentage) for
      the Lys in CC, HOC2, and HOC3 relative to the Lys in L-Lys x HC1 were 65 +/- 10,
      72 +/- 10, and 91 +/- 8, respectively. The results of this study indicated that
      digestibility of amino acids and bioavailability of Lys in HOC are equal to or
      greater than those in CC.

PMID- 9657614
TI  - An evaluation of threonine requirements of young turkeys.
AB  - Two experiments were conducted to evaluate the Thr requirements of male Large
      White turkeys from 3 to 6 and 6 to 9 wk of age. One group of turkeys was fed to 3
      wk using nutritionally adequate diets and fed test diets from 3 to 6 wk; another
      group of turkeys was fed to 6 wk using nutritionally adequate diets and fed test
      diets from 6 to 9 wk. Test diets were composed of peanut meal, soybean meal,
      corn, and grain sorghum as intact protein sources and were supplemented with
      amino acids. Peak performance of turkeys fed the test diets was equivalent to
      that of turkeys fed conventional corn-soybean meal diets formulated to meet NRC
      (1994) standards. Estimates of Thr requirements for weight gain were 0.92 and
      0.86% for 3 to 6 and 6 to 9 wk, respectively. For feed conversion, estimates of
      Thr requirements were 0.87% and 0.84% for 3 to 6 and 6 to 9 wk, respectively. The
      results of the two experiments reported herein would suggest that the Thr
      requirements suggested by NRC (1994) for turkeys up to 9 wk of age are safe
      estimates; they may slightly overestimate the requirements but not by a large
      margin.

PMID- 9657615
TI  - Effects of dietary taurine on egg weight.
AB  - Two experiments were conducted to determine whether taurine supplementation to
      laying hens would influence laying performance. In Experiment 1, a total of 120
      White Leghorn hens were fed diets supplemented with 0, 0.25, or 0.5% taurine for
      5 wk. Egg weight was reduced significantly by supplementing 0.25 and 0.5%
      taurine; however, taurine did not affect other laying performance variables. In
      Experiment 2, a total of 240 White Leghorn hens were fed diets supplemented with
      0 or 0.5% taurine and 0 or 0.1% methionine for 7 wk. Egg weight was decreased due
      to supplementing taurine in the diets; however, dietary methionine did not affect
      egg weight, and there was no interaction between dietary taurine and methionine.
      These results suggest that dietary taurine has the potential to decrease egg
      weight without affecting egg production, feed conversion, or body weight.

PMID- 9657616
TI  - Locus-specific diagnostic tests for endogenous avian leukosis-type viral loci in
      chickens.
AB  - The genome of the chicken, Gallus gallus, contains endogenous proviral elements
      (ALVE elements or ev genes) that display a high degree of similarity to the Avian
      Leukosis class of retroviruses. The ALVE proviruses are known to modulate
      physiological processes of the host birds. Different ALVE elements retain
      variable portions of the complete, prototype viral genome, and each provirus
      resides in its own specific location within the host genome. Thus, each ALVE
      element has its own particular potential to modulate host physiology depending on
      the nature of its integration site, the completeness of the proviral genome, and
      the level of expression of the locus. It is important, therefore, to be able to
      establish the ALVE element profiles of chickens quickly and accurately, both in
      the laboratory and in a commercial setting. The current method of choice for
      simple, quick, and accurate typing is the polymerase chain reaction (PCR). This
      paper reviews the present status of PCR typing of ALVE proviruses and lists the
      assay protocols for 19 different elements. In addition, it compares the insertion
      sites of these elements in an effort to identify common motifs at ALVE
      integration sites.

PMID- 9657617
TI  - Characterization of turkey spermiophages with regard to traits common to
      macrophages.
AB  - Turkey peritoneal exudate cells (PEC) and spermiophages (SMO) were assayed for
      characteristics of macrophages. The PEC elicited by i.p. injection of 3% Sephadex
      and SMO isolated from semen using Percoll were cultured in Dulbecco's Modified
      Eagle Medium supplemented with 20% bovine calf serum (DMEM-20) for 24 h at 41 C
      in 5% CO2 to provide adherent cells for assays. Most PEC and SMO showed esterase
      activity (99.3 +/- 0.6 and 98.8 +/- 0.9%, respectively), and exhibited
      nonspecific phagocytosis of carbon (89.5 +/- 3.6 and 95.3 +/- 0.6%,
      respectively), zymosan (26.5 +/- 7.6 and 24.3 +/- 2.5%, respectively), bacteria
      (11.3 +/- 0.8 and 9.3 +/- 0.3%, respectively), and opsonized and nonopsonized
      SRBC. Maximum uptake of SRBC was seen by 2 h for PEC but not until 4 h for SMO.
      At time of maximum uptake, SRBC were noted in 35 to 40% of PEC but only in 15 to
      20% of SMO. Turkey IgG-FITC bound to both PEC and SMO, but goat anti-turkey IgG
      FITC bound only to SMO. Increased nitrite was found in turkey semen after 24 h
      storage, with highest levels in samples in which SMO were added. Nitrite
      production was demonstrated using adhered PEC, but SMO could not be tested due to
      low cell numbers. This research clearly identifies SMO as having macrophage-like
      activities. Accordingly, these cells may possess the ability to process and
      present antigen via histocompatibility receptors. Such activity could lead to
      immune directed responses, including antibody production or activation of
      cytotoxic T-lymphocytes.

PMID- 9657618
TI  - Echocardiographic evaluation of cardiac structure and function in broiler and
      Leghorn chickens.
AB  - This study was conducted to validate echocardiography in chickens, and to compare
      cardiac structure and function between broiler and Leghorn chickens. Diameters of
      the right and left ventricles, and thicknesses of the left ventricular free wall
      and the interventricular septum were measured echocardiographically in 5- and 7
      wk-old chickens from both lines. Images were obtained from minimally restrained,
      standing birds using a 7.5 MHz probe placed in a parasternal position. End
      systolic and end-diastolic echocardiographic measurements were compared with post
      mortem measurements of the same variables. Comparisons resulted in correlation
      coefficients greater than 0.70 between in vivo (echocardiographic) and post
      mortem measurements of the same variables, with post-mortem measurements more
      closely resembling end-diastolic echocardiographic measurements. After being
      normalized to body weight, post-mortem myocardial thicknesses, aortic and left
      ventricular diameters, heart weight at 5 wk of age, and left ventricular weight
      at 7 wk of age were smaller in broiler than in Leghorn chickens.
      Echocardiographic parameters, including ventricular wall thicknesses, ventricular
      diameters, and left ventricular fractional shortening, were also smaller in the
      broiler chicken. Right ventricular fractional shortening did not differ between
      the chicken lines. These results indicate that echocardiography is a useful
      noninvasive technique for in vivo evaluation of cardiac structure and function in
      the chicken, and that broiler chickens have a relatively smaller structural and
      functional heart than Leghorn chickens.

PMID- 9657619
TI  - Effects of varying aeration treatment on fertilizing capacity of semen diluted
      with perfluorochemical emulsion and stored for twenty-four hours.
AB  - The effects of perfluorochemical (PFC) oxygen carriers in turkey semen diluents
      on fertility and hatchability was measured for a 10-wk period. Semen was diluted
      (1:1) with Beltsville Poultry Semen Extender (BPSE) or BPSE:FC-75, an emulsified
      mixture of BPSE and perfluorobutyltetrahydrofuran (technical grade) (FC-75) and
      stored for 24 h at 5 C with agitation (150 rpm) and aeration with either air,
      nitrogen (100%), or oxygen (100%). Sperm concentration and percentage of dead
      sperm were determined prior to and after storage. Sperm concentration (8.35 to
      9.21 x 10(9) per milliliter) was not significantly affected by the type of
      diluent or aeration gas, and only stored semen diluted with BPSE: FC-75 and
      aerated with nitrogen had increased percentage of dead sperm. Diluent type did
      not affect the percentage of fertilized eggs; however, fertility and hatchability
      for both diluent treatments with nitrogen aeration was significantly lower (P <
      or = 0.05) than for the semen treatments with air or oxygen aeration.
      Hatchability for semen diluted with BPSE:FC-75 and aerated with oxygen (63.7%)
      was significantly higher (P < or = 0.05) than that for BPSE-diluted semen aerated
      with oxygen (43.2%). Although use of oxygen carrying fluorocarbon emulsified with
      BPSE did not further improve fertility when the semen was stored for 24 h while
      oxygenated and mechanically agitated, a beneficial effect was noted for
      hatchability. The fact that nitrogen severely depressed fertility confirms that
      the beneficial effects of agitation are due to oxygenation of the spermatozoa.
      Therefore, further studies of oxygen carriers in semen are warranted.

PMID- 9657620
TI  - Dietary methionine intake effects on egg component yield, composition,
      functionality, and texture profile analysis.
AB  - The influence of supplemental Met levels ranging from 413 to 556 mg per hen per d
      (mg/HD) on liquid egg component yield, composition, and functionality was
      examined in mature layers (29 wk of age). Egg weight, component yield, solids,
      and CP content of albumen and yolk were determined. Texture profile analysis,
      feed ingredient functionality testing, and PAGE were conducted to determine
      whether increased egg total solids and CP content resulted in altered egg
      component functionality or electrophoretic protein banding pattern. Albumen
      component yield increased significantly on a mass basis at 507 and 556 mg/HD Met
      compared to 413 mg/HD Met. Yolk mass yield was significantly increased at 556
      mg/HD Met compared to 413 mg/HD Met. Consumption above 413 mg/HD Met resulted in
      significantly increased albumen total solids and protein. Yolk solids were not
      significantly different; however, yolk CP was significantly increased at 507 and
      556 mg/HD Met compared to 413 mg/HD Met. Albumen and yolk functionality at 413
      and 507 g/HD Met were not significantly different in relation to cake volume or
      height. Emulsion separation at 120 min was significantly increased for 556 mg/HD
      Met compared to 413 and 507 g/HD Met. There were no significant differences in
      hardness or springiness of albumen and yolk gel plugs and electrophoretic protein
      banding patterns. Increased understanding of the influence of Met on liquid egg
      yield and composition may provide the egg producer with an effective and
      advantageous management technique for shell egg production specifically managed
      to maximize liquid egg product.

PMID- 9657621
TI  - Time course of complete normalization of left ventricular hypertrophy during long
      term antihypertensive therapy with angiotensin converting enzyme inhibitors.
AB  - Metaanalyses have indicated that ACE inhibitors are more effective than other
      first-line therapies in reducing left ventricular hypertrophy (LVH). The average
      treatment period, however, was only approximately 6 months. The aim of the
      present study, therefore, was to clarify the time course and degree of reversal,
      and primarily to find out in how many patients a complete normalization of LVH
      can be achieved. Secondly, we sought to determine whether atrial enlargement can
      be reduced. Previously untreated hypertensive patients (mean age 46.3 +/- 9
      years, eight women, 15 men) with echocardiographically confirmed LVH (left
      ventricular mass index ([LVMI] > 125 g/m2 for men; > 110 g/m2 for women) were
      prospectively treated over a 3-year treatment period with quinapril. Nine
      patients received 10 mg quinapril, 12 received 20 mg of quinapril daily, and five
      patients additionally received 25 mg hydrochlorothiazide. The time course of
      changes in LVMI, relative wall thickness, left atrial size, fractional
      shortening, and diastolic function was evaluated and ambulatory blood pressure
      monitoring (ABPM) and an exercise test were performed every 6 months. After a
      mean treatment period of only 7.5 months, there was a significant (P < .001),
      17.5% decrease in LVMI with a further continuous and significant (P < .001)
      decrease of 38.6% after 38.3 +/- 3 months of therapy. In 90.5% of the patients a
      complete reversal of LVH was achieved. Fractional shortening increased
      significantly, the maximum being 14.6% after 38.3 +/- 3 months. The peak
      early/atrial velocity (E/A) ratio increased significantly (P < .01) after just
      7.5 +/- 3.1 months with no further changes during follow-up. There seemed to be a
      parallel change with the decrease in left atrial dimension, where the most
      important decrease occurred after only 7.5 +/- 3.1 months (P < .01), with a
      further continuous reduction. Our study clearly shows that maximum reversal of
      LVH is a time-consuming process and that an essential goal of antihypertensive
      therapy should be not only a reduction in LVH but also a normalization in LV
      mass, left atrial size, and in diastolic dysfunction.

PMID- 9657622
TI  - Comparison of spirapril, isradipine, or combination in hypertensive patients with
      left ventricular hypertrophy: effects on LVH regression and arrhythmogenic
      propensity.
AB  - This study was designed to evaluate in 45 hypertensive patients with left
      ventricular hypertrophy (LVH) the effects of a 6-month course with one of three
      different antihypertensive regimens (the calcium channel blocker isradipine, the
      angiotensin converting enzyme inhibitor spirapril in monotherapy, or a
      combination of the two drugs, n = 15 per group) on blood pressure, LVH
      regression, and various functional correlates of LVH. All three treatment
      modalities decreased significantly LV mass index by an average of 10%, although
      the combination had the greatest blood pressure-lowering effect and spirapril had
      the least, as assessed by office resting pressures, ambulatory monitoring, and
      isometric grip testing. There was no correlation between magnitude of blood
      pressure lowering and degree of LVH regression. The effects of treatment on
      pressor hormone profiles differed among groups, as spirapril tended to suppress
      angiotensin II and norepinephrine, whereas isradipine had opposite effects.
      Exercise tolerance was prolonged by all three regimens, but significantly more by
      the combination. All three regimens decreased significantly the double product by
      10% to 15%. Indices of electrophysiologic stability calculated from analysis of
      ambulatory electrocardiogram exhibited significant improvement in several
      parameters such as QRS duration, presence of late potentials, and measures of
      heart rate variability, resulting in fewer episodes of simple or complex
      ventricular arrhythmia. We conclude that all three regimens produce significant
      LVH regression associated with improved functional capacity and electrical
      stability. These results reflect the sum of the differential hemodynamic and
      hormonal effects exerted by each treatment modality.

PMID- 9657623
TI  - Vagal cardiac activity in essential hypertension: the effects of metoprolol and
      ramipril.
AB  - Cardiovascular parasympathetic activity is attenuated in essential hypertension.
      Both beta-adrenoceptor antagonists and angiotensin converting enzyme inhibitors
      have been reported to increase vagal modulation of heart rate and baroreflex
      sensitivity, but the relations between the antihypertensive and vagal cardiac
      effects of these drugs have remained unclear in essential hypertension. In the
      present study we evaluated the effects of a 4-week crossover monotherapy with
      metoprolol and ramipril on spectrum analysis indices of heart rate variability in
      the supine rest and head-up tilted positions, baroreflex sensitivity
      (phenylephrine method), and 24-h ambulatory blood pressure (BP) in 12 formerly
      untreated stage 1-2 essential hypertensive patients. Compared to the pretreatment
      values, both drugs decreased BP similarly and significantly. However, the drugs
      showed different effects on cardiac vagal activity: metoprolol increased
      significantly mean R-R interval, R-R interval total, and high-frequency
      variability at supine rest and baroreflex sensitivity, but ramipril did not
      significantly affect these variables. The metoprolol-induced decrease in
      ambulatory BP correlated with the prolongation of the R-R interval and the
      increase of high-frequency variability at supine rest. The present data show that
      4-week treatment with metoprolol increases tonic and reflex vagal cardiac
      activity, whereas ramipril does not affect vagal cardiac control in essential
      hypertension. Increase in vagal activity may contribute to the BP-lowering effect
      of metoprolol in hypertensive patients.

PMID- 9657624
TI  - Acute cardiovascular effect of 1,25-dihydroxycholecalciferol in essential
      hypertension.
AB  - A role for vitamin D in the pathophysiology of essential hypertension has
      frequently been suggested, but acute direct effects on blood pressure, cardiac
      output, renal hemodynamics, or hormones have not previously been demonstrated.
      The rapid effects of 1,25-dihydroxycholecalciferol (1,25-D) were assessed over
      120 min after a bolus injection (0.02 microg/kg body weight) in eight men with
      essential hypertension and in nine healthy men. A placebo group of 10 healthy men
      was also included. Ionized calcium was monitored closely during the study, and
      was kept constant with a clamping technique. In the hypertensive patients, a
      transient increase in blood pressure and a reciprocal fall in cardiac output
      measured by a CO2 rebreathing technique (-15%, P < .05) were observed after 1,25
      D injection. In the control group, both blood pressure and cardiac output
      remained unchanged. The glomerular filtration rate, effective renal plasma flow,
      and urinary sodium and water excretions were unchanged in both groups. Plasma
      levels of atrial natriuretic peptide at baseline were higher in the hypertensive
      patients than in the control subjects (P < .02); plasma levels of renin,
      aldosterone, norepinephrine, endothelin, and parathyroid hormone(1-84) were
      similar in the two groups. None of these hormones was affected during the
      observation time after the injection of 1,25-D. In conclusion, acute
      administration of 1,25-D caused a fast and likely nongenomic-mediated decrease in
      cardiac output in patients with essential hypertension, which together with a
      transient BP increase implies a 1,25-D-induced increase in total peripheral
      resistance. These data suggest an enhanced cardiovascular responsiveness to 1,25
      D in hypertensive compared to healthy normotensive subjects.

PMID- 9657625
TI  - Endogenous digoxin-like immunoactivity in subjects with diabetes mellitus and
      hypertension.
AB  - The serum concentrations of digoxin-like immunoactivity (DLIA) were measured in
      99 patients: 20 healthy volunteers (HV), 15 patients with insulin-dependent
      diabetes mellitus (IDDM), 14 patients with non-insulin-dependent diabetes
      mellitus without hypertension taking oral hypoglycemic (OHA) agents (NIDDM/-HT),
      11 patients with NIDDM without hypertension taking insulin (NIDDM/-HT+INS), 12
      NIDDM patients with hypertension taking OHA (NIDDM/+HT), nine NIDDM patients with
      hypertension taking insulin (NIDDM/+HT/+INS), 10 patients with essential
      hypertension with normal insulin levels (HT/-HI), and in eight patients with
      essential hypertension with hyperinsulinemia (HT/+HI). The numbers (%) of
      subjects with DLIA levels above the detection limit of the assay used (> 0.1
      nmol/L) were, in the NIDDM/-HT group, 12/14 (85.7%) and in the NIDDM/+HT group,
      9/12 (75%), significantly higher (P < .05) than in the HV (7/20; 35%), IDDM
      (3/15; 20%), and HT/-HI groups (2/10; 20%). The number and percentage of subjects
      with DLIA levels above the detection limit in the HT/+HI group was six of eight
      (75%), significantly (P < .05) higher than in the IDDM and HT/-HI groups, and
      tended to be higher than in the HV group (P < .055). Means and SD of serum DLIA
      levels (nmol/L) in the NIDDM/-EH (0.18/0.09) and NIDDM/+EH (0.19/0.15) groups
      were significantly higher (P < .05) than in the HV (0.09/0.07), IDDM (0.05/0.05),
      and EH/-HI (0.06/0.06) groups. DLIA levels in the HT/+HI group (0.15/0.12) were
      significantly higher (P < .05) than in the IDDM and HT/-HI groups. The percentage
      of DLIA levels above the detection limit, as well as the mean and SD of DLIA in
      the NIDDM group taking OHA, did not differ from those in subjects taking insulin.
      In all subjects studied (n = 99), DLIA correlated with C-peptide (r = 0.30; P <
      .01) and glomerular filtration (GF) (r = -0.21; P < .05). After exclusion of
      insulin-treated patients, DLIA correlated significantly with plasma glucose (PG;
      r = 0.25; P < .05), immunoreactive insulin (IRI; r = 0.41; P < .001), C-peptide
      (r = 0.27; P < .05), and GF (r = -0.26; P < .05) (n = 64). Correlation of DLIA
      with IRI (r = 0.33; P < .05; n = 38) also persisted after exclusion of patients
      taking insulin and those with DLIA levels below the detection limit. Similarly,
      DLIA also correlated with C-peptide (r = 0.64; P < .05) and IRI (r = 0.70; P <
      .05) in the subgroup of 10 patients with the highest levels of DLIA (> 0.25
      nmol/L). None of the sera (n = 15) with different DLIA concentrations (0.0-0.38
      nmol/L) exhibited K-pNPPase (Na+-K+-ATPase) inhibitory activity. In conclusion,
      this work demonstrated elevated serum DLIA in NIDDM and HT/+HI patients, and its
      correlation with IRI and GF. However, due to the fact that the chemical nature
      and biologic properties of DLIA are still a matter of debate, it is too early to
      speculate whether the elevation of DLIA is just a secondary result associated
      with HI and reduced GF, or whether it also has pathophysiologic consequences.
      Nevertheless, in both cases the elevated concentrations of substances with DLIA
      and their interference with antidigoxin antibodies may affect therapeutic
      monitoring of digitalization in NIDDM and HT/+HI patients. Also, the elevated
      DLIA could subclassify these patients. The significance of such
      subclassifications (pathophysiologic, therapeutic, or prognostic), however, will
      need further investigation.

PMID- 9657626
TI  - Acute effects of cigarette smoking on platelet function and plasma catecholamines
      in hypertensive and normotensive men.
AB  - In this randomized controlled crossover study essential hypertensive men (n = 13)
      and matched normotensive controls (n = 18) were examined before and during
      cigarette and sham smoking to assess the acute effects of smoking on platelets
      and plasma catecholamines. Platelet activity in vivo was determined by
      measurements of the released alpha-granule constituent beta-thromboglobulin (beta
      TG) in plasma and in urine. Urinary high molecular weight beta-TG and venous
      plasma epinephrine increased significantly during smoking in the hypertensive
      group, but not among the normotensive men. Thus, cigarette smoking induces a mild
      platelet release reaction and also elicits a significantly higher epinephrine
      response in hypertensive men compared to normotensive controls.

PMID- 9657627
TI  - Effects of an ACE inhibitor and a calcium channel blocker on cardiovascular
      autonomic nervous system and carotid distensibility in patients with mild to
      moderate hypertension.
AB  - We investigated the relationship between cardiovascular autonomic nervous system
      function and carotid arterial distensibility during treatment with an angiotensin
      converting enzyme inhibitor (derapril) or a calcium channel blocker (manidipine)
      for hypertension. In 37 patients with hypertension, autonomic function was
      assessed by heart rate variability and baroreceptor sensitivity using
      phenylephrine injection. Left ventricular mass index and carotid arterial
      distensibility were assessed by ultrasound examinations. Before the medication,
      both baroreceptor sensitivity and heart rate variability correlated with carotid
      arterial distensibility, but not with left ventricular mass index by multiple
      regression analysis. Subsequently, patients were randomly allocated into two
      groups, derapril (n = 18) and manidipine (n = 19) for 20 weeks. At the end of the
      study, the change in baroreceptor sensitivity correlated with change in carotid
      arterial distensibility (r = 0.41, P < .05), but not with change in left
      ventricular mass index. Although derapril and manidipine decreased blood pressure
      and left ventricular mass index to the same extent, the former improved heart
      rate variability, baroreceptor sensitivity (5.0 +/- 1.9 --> 5.6 +/- 2.0 msec/mm
      Hg), and carotid arterial distensibility (2.1 +/- 0.8 --> 2.5 +/- 1.0 %kPa), but
      the latter did not improve them at all. Thus, impairment of the autonomic balance
      was related to the impairment of carotid arterial distensibility in hypertension;
      derapril, but not manidipine, significantly improved these abnormalities.

PMID- 9657628
TI  - Effect of amlodipine versus felodipine extended release on 24-hour ambulatory
      blood pressure in hypertension.
AB  - Amlodipine and felodipine are calcium antagonists of the dihydropyridine type.
      The elimination half-life of amlodipine is longer than that of felodipine. To
      study whether the different elimination rates of the drugs were reflected in
      different duration of blood pressure (BP) control, we compared amlodipine and
      felodipine extended release (ER) by both conventional clinic BP 24 h after drug
      intake and 24 h ambulatory BP monitoring (ABPM), with special reference to
      nighttime and morning blood pressure. Two hundred and sixteen patients with
      primary hypertension (supine diastolic BP, 95 to 115 mm Hg) were randomized to
      receive amlodipine or felodipine ER in a multicenter study. The starting dose of
      both drugs was 5 mg. If the target clinic diastolic BP (90 mm Hg) had not been
      achieved after 4 weeks the dose was increased to 10 mg. Twenty-four-hour ABPM was
      performed with the subjects taking placebo medication before randomization and
      after 4 and 8 weeks undergoing active treatment. Significantly more patients
      responded after 4 weeks of treatment with amlodipine (50%) as compared with
      felodipine (33%) (P = .013). ABPM during daytime (07:00 to 23:00) was similar
      during both treatments, but nighttime systolic (P = .026) and diastolic (P =
      .019) BP was more effectively reduced by amlodipine than by felodipine. After 8
      weeks 82% achieved the target pressure with amlodipine and 69% with felodipine (P
      = .036 for the difference). Amlodipine seems to be more effective than felodipine
      when the drugs are compared in the same dose, with regard to the effect on clinic
      BP 24 h after dosing and to ambulatory BP during the night. The longer
      elimination half-life of amlodipine as compared to felodipine is the probable
      reason for this finding.

PMID- 9657629
TI  - Antihypertensive agents prevent nephrosclerosis and left ventricular hypertrophy
      induced in rats by prolonged inhibition of nitric oxide synthesis.
AB  - We investigated the ability of the angiotensin converting enzyme (ACE) inhibitor
      imidapril hydrochloride, and of the calcium channel blocker amlodipine besilate,
      to prevent nephrosclerosis and left ventricular hypertrophy (LVH) in rats with
      hypertension induced by chronic inhibition of nitric oxide (NO). Male Wistar rats
      were given distilled water (control), NG-nitro-L-arginine methyl ester (L-NAME)
      500 mg/L, L-NAME plus imidapril 10 mg/L or 100 mg/L, or L-NAME plus amlodipine 50
      mg/L or 100 mg/L in the drinking water (n = 10-12). We then collected 24-h urine
      samples at 2, 4, and 6 weeks, obtained blood samples at 6 weeks, and
      histologically examined the kidney and heart. L-NAME markedly reduced the levels
      of NO metabolites in serum and urine while increasing the tail-cuff blood
      pressure, the urinary albumin level (1.90 +/- 0.65 v 0.05 +/- 0.02 mg/day/100 g
      in control), and the area of the left ventricular wall (83.3 +/- 3.0 v 69.8 +/-
      1.8 mm2 in control). Nephrosclerosis and myocardial interstitial fibrosis were
      documented histologically. The plasma renin activity was significantly higher in
      rats treated with L-NAME than in the control rats. The concomitant administration
      of imidapril (10 mg/L) with L-NAME completely normalized the tail-cuff pressure,
      the LVH (70.8 +/- 1.8 mm2), the albuminuria (0.05 +/- 0.01 mg/day/100 g), and the
      histologic changes. Amlodipine (50 mg/L) also ameliorated the L-NAME-induced
      effects, but to a lesser extent. Thus, the chronic inhibition of NO synthesis in
      rats produced nephrosclerosis and LVH that were effectively prevented by giving
      imidapril at a dose lower than that of amlodipine. We conclude that ACE
      inhibitors can prevent nephrosclerosis and LVH even in the presence of a
      reduction in NO production, implying that in rats the inhibition of the renin
      angiotensin system is more effective than the blockade of calcium channels in
      preventing hypertensive tissue injury.

PMID- 9657630
TI  - Role of nitric oxide in cocaine-induced acute hypertension.
AB  - Cocaine causes acute hypertension by blocking catecholamine reuptake. There is
      evidence that it also impairs the peripheral endothelial nitric oxide system,
      which is normally vasodilatory. We further explored the role of nitric oxide in
      cocaine-induced vasoconstriction in anesthetized rats, and in vitro by using
      isolated carotid artery segments. Cocaine administered intravenously in rats
      increased mean arterial pressure by 30 to 40 mm Hg within 1 min. This effect was
      dose dependent and the maximum effect was observed at a dose of 1.25 mg/kg. The
      prototype catecholamine norepinephrine induced a similar increase in blood
      pressure. When rats were pretreated with NG-monomethyl-L-arginine (L-NMMA, a
      blocker of nitric oxide) and challenged with cocaine, the increase in blood
      pressure was blocked by 80%, whereas pretreatment with L-NMMA did not block
      norepinephrine-induced vasoconstriction. Both cocaine and norepinephrine also
      induced an immediate vasoconstriction in isolated carotid artery preparations.
      The in vitro vasoconstriction induced by cocaine was blocked by pretreatment with
      L-NMMA, whereas L-NMMA did not block the norepinephrine-induced vasoconstriction
      in vitro. Furthermore, carotid artery stripped of endothelium responded to
      norepinephrine but failed to respond to L-NMMA or cocaine. S-nitroso-N-acetyl-D,L
      penicillamine (SNAP)-a precursor of nitric oxide- stimulated nitric oxide
      production in control coronary artery fragments. When these fragments were
      incubated with cocaine there was a 20% reduction in the production of nitrite
      oxide. These results suggest that cocaine exerts its peripheral vasoconstriction
      at least in part by inhibiting local vasodilator nitric oxide.

PMID- 9657631
TI  - Tissue-specific regulation of growth factors and clusterin by angiotensin II.
AB  - Angiotensin II (ANG II) has been implicated in the hypertrophic and fibrotic
      responses of the heart and kidney to systemic hypertension. To determine whether
      these actions of ANG II are related to tissue-specific stimulation of growth
      factors, we infused adult Sprague-Dawley rats with ANG II at 50 ng/min (low
      dose), 100 ng/min (high dose), or vehicle for 1 week. Rats receiving vehicle or
      low-dose ANG II were normotensive with normal plasma aldosterone concentration,
      whereas rats receiving high-dose ANG II were hypertensive with increased plasma
      aldosterone. Tissue fibrosis was quantified morphometrically, and messenger RNA
      (mRNA) for transforming growth factor-beta1 (TGF-beta1) and prepro-epidermal
      growth factor (EGF) was measured in liver, heart, and renal glomeruli and
      tubules. In addition, mRNA was determined for clusterin, a glycoprotein expressed
      in response to tissue injury. Compared to vehicle, low-dose ANG II increased TGF
      beta1 expression in glomeruli, tubules, and heart, but not in liver, and
      increased EGF expression in renal tubules only. High-dose ANG II decreased
      clusterin expression in liver only. Fibrosis was induced by low- and high-dose
      ANG II in kidney and heart, but not in liver. We conclude that ANG II selectively
      stimulates TGF-beta1 mRNA in the heart and kidney, which may contribute to
      cardiac and renal interstitial fibrosis resulting from activation of the renin
      angiotensin system independent of hypertension. By stimulating cellular
      proliferation, selective stimulation by ANG II of EGF in renal tubules may
      amplify the effects of TGF-beta1. Suppression of clusterin expression in the
      liver of hypertensive rats may represent a specific response to high levels of
      circulating ANG II or a response to hypertensive injury.

PMID- 9657632
TI  - A limited renal injury may cause a permanent form of neurogenic hypertension.
AB  - Previously, we have shown that an acute injury to the kidney produced by an
      intrarenal injection of phenol causes an immediate increase in blood pressure and
      in norepinephrine (NE) secretion from the posterior hypothalamus. The studies
      suggest that in this model afferent impulses from the kidney to central
      integrative structures in the brain may be responsible for the increase in blood
      pressure. To further evaluate whether a renal injury caused by the intrarenal
      injection of phenol leads to a permanent elevation of blood pressure and whether
      this is mediated by increased sympathetic nervous system activity, we examined
      the chronic effects (4 weeks) of an intrarenal injection of 50 microL of 10%
      phenol on blood pressure and NE secretion from the posterior hypothalamus.
      Systolic blood pressure increased from 128 +/- 2.1 to 176 +/- 1.5 mm Hg (P < .01)
      4 weeks after receiving the intrarenal injection of phenol, but it did not change
      in rats that received the vehicle (128 +/- 2.4 and 135 +/- 1.7 mm Hg) and in rats
      that were subjected to renal denervation (127 +/- 3.4 and 124 +/- 1.0 mm Hg). The
      secretion of NE from the posterior hypothalamic nuclei was greater (P < .01) in
      rats that received phenol (253 +/- 9.6 pg/mL) than in controls (158 +/- 8.6
      pg/mL) and denervated rats (170 +/- 2.1 pg/mL). These studies have shown that a
      limited injury to one kidney may cause a permanent elevation of blood pressure
      and this is associated with increased sympathetic nervous system activity.

PMID- 9657633
TI  - Human leukocyte antigens and malignant essential hypertension.
AB  - The purpose of this study was to investigate an association between human
      leukocyte antigens (HLA) and the susceptibility to malignant hypertension. The
      presence of HLA-A, -B, -DR, and -DQ was determined in 33 white and in 23 mulatto
      Brazilian patients with malignant essential hypertension. No statistically
      significant differences were detected between patients and control subjects. It
      is nevertheless important to note that we have observed an increased frequency of
      DR3 in the mulatto patients (34.8% v 21.4%). We consider that this finding
      supports the existence of an HLA-DR3 association with hypertension in the black
      population, as has been claimed by other authors.

PMID- 9657634
TI  - Association between left atrial enlargement and target organ damage in essential
      hypertension.

PMID- 9657635
TI  - Is sexual dysfunction in hypertensive women uncommon or understudied?

PMID- 9657636
TI  - Who manages hypertensive patients? The primary care-hospital interface.
AB  - The term hypertension is used loosely to cover the right-hand skew of the blood
      pressure frequency distribution. It embraces almost 20% of the population, of
      which the major part will fare as well with or without treatment, and a much
      smaller group of true patients in whom underlying causes are or will be found,
      the causes being mainly genetic. The role of the primary care physicians is in
      the initial detection of patients in both groups, and in the reduction of
      attributable risk by collectively pushing the blood pressure distribution to the
      left. The role of the specialists is effective diagnosis, prognosis, and
      management of the more narrowly defined hypertensive patients, to reverse their
      high relative risk of complications, ideally at a stage before they become at
      high absolute risk.

PMID- 9657637
TI  - Detection and control of hypertension in the population: the United States
      experience.
AB  - Trends in prevalence, awareness, treatment, and control of hypertension in the
      adult US population are reported. The data are from the National Health and
      Nutrition Examination Surveys (NHANES), carried out in four separate surveys, the
      last being NHANES III, 1988-1991. The age-adjusted prevalence of hypertension at
      > or = 160/95 mm Hg declined from 20% to 14%, and at > 140/90 mm Hg it declined
      from 36.3% to 20.4% in NHANES III. Hypertension awareness increased significantly
      to as high as 89% for those with blood pressures > or = 160/95 mm Hg. For all
      people with blood pressure > or = 160/95 mm Hg, nearly 64% have it controlled
      below that level, but only 29% have their blood pressure controlled below 140/90
      mm Hg. Although the data from these surveys are encouraging, there are still too
      many people in the United States with uncontrolled hypertension.

PMID- 9657638
TI  - Treatment of raised blood pressure in the population: the Canadian experience.
AB  - The Canadian Heart Health Survey, in which all 10 Canadian provinces participated
      using a standardized protocol, provides data from 23,129 randomly selected
      participants. The hypertension component of this survey indicates a prevalence of
      22%; among these hypertensives, 59% were aware of their elevated blood pressure
      status. The breakdown of aware hypertensives indicates that 16% of those were
      treated and controlled, 24% were treated but not controlled, and 19% were neither
      treated nor controlled. In terms of drug prescription pattern, angiotensin
      converting enzyme inhibitors, including angiotensin II antagonists, command the
      maximum market share of 27.7% ($36 million), followed by diuretics, calcium
      channel blockers, beta3-blockers, and others. Although hypertension awareness and
      control have improved in the past 25 years, sustained efforts are warranted to
      control hypertension in Canada.

PMID- 9657639
TI  - Treatment of high blood pressure in Germany.
AB  - The reunification of Germany has made it possible to compare the health care in
      two independently developed social structures. The prevalence of hypertension was
      considerably greater in East German men and women, compared with West German men
      and women, although salt intake was lower in East Germany than in West Germany.
      Cardiovascular mortality was correspondingly greater. A centralized public health
      effort was used in East Germany, whereas in West Germany, the activities were
      decentralized and to a large extent dependent on private philanthropists. In the
      last two decades, cardiovascular mortality declined in West German men and women,
      whereas the same was not true for East German men and women. Hypertension
      incidence, awareness, treatment, and control have improved slightly in Germany,
      but not enough to explain the improved morbidity figures. Twenty percent of men
      and women remain unaware of their hypertension, 40% are aware but not treated,
      and only half are aware and controlled. Complacency is unjustified in Germany and
      much needs to be done.

PMID- 9657640
TI  - Hypertension: the United Kingdom experience.

PMID- 9657641
TI  - Hypertension: the East European experience.
AB  - Some differences (and similarities) between Eastern Europe and the rest of the
      Continent are presented regarding the treatment of hypertension. Based on data
      from the WHO Monitoring Trends and Determinants in Cardiovascular Diseases
      (MONICA) study, the prevalence of hypertension, and the proportion of
      uncontrolled hypertension, is clearly higher in Eastern Europe. According to one
      local long-term observer, a trend for further increases in prevalence is
      discernable. Comparative drug consumption studies are desirable. Regarding
      national experiences with hypertension and health care in general, there are also
      some important sociocultural differences; anecdotal observations are reported
      that support this assertion.

PMID- 9657642
TI  - Prevalence, treatment, and control of hypertension in the French population: data
      from a survey on high blood pressure in general practice, 1994.
AB  - A survey was conducted in a cohort of 235 general practitioners (GP) selected by
      Sofres Medical who were representative of the French medical population, to
      measure the percentage of patients with hypertension, treated hypertensives and
      patients with controlled hypertension. Data were collected over 1 week of office
      consultation. Practitioners were initially instructed to use the same type of
      mercury sphygmomanometer, equipped with pneumatic cuffs of different sizes. Three
      consecutive blood pressure (BP) measurements were made and the last two were
      recorded. Practitioners had to carry out their own survey over a period of 1 week
      on all patients > 18 years of age who visited their offices. Patients were
      considered as hypertensive (HP) if the mean of the two recorded BP measurements
      was > or = 140/90 mm Hg or if they were taking antihypertensive drug treatment.
      Three cutoff points were used to define controlled hypertension: < 140/90 mm Hg
      (overall population of HP), < 160/95 mm Hg (HP < 65 years of age), and < 160/90
      mm Hg (HP > or = 65 years of age). Among 12,351 patients (mean age, 48.6 years;
      women, 58%), 5020 were HP, (41%) of whom 2035 were without treatment (41%) and
      2985 were receiving antihypertensive drug treatment (59%). Two hundred-thirty
      patients (4.6%) remained at high risk with moderate or severe hypertension (BP >
      or = 180 [systolic] or 105 [diastolic] mm Hg), ie, 1 patient/week/GP. The study
      confirms the high prevalence of hypertension in general practice and shows that 7
      of 10 patients have an acceptable control of their BP (< 160/95 or < 160/90 mm Hg
      according to age) but only 24% of treated HP achieved the target of a BP level <
      140/90 mm Hg, representing 28% of the 18 to 64 year old group and 21% of the
      elderly group. French GP did not choose an optimal control, and the medical
      community is waiting for answers to crucial questions, ie, does optimal BP
      control significantly improve the absolute cardiovascular risk? How far should
      blood pressure be lowered?

PMID- 9657643
TI  - Actions implemented to improve hypertension control in Spain.
AB  - Hypertension prevalence is estimated at approximately 30% of the adult population
      in Spain, using the 140/90 mm Hg cutoff. This represents a heavy public health
      burden when compared with other European countries, although the direct cost per
      person is one of the lowest in Europe. The programs implemented regionally since
      1985 are presented here. As a result of them, a decade later the number of
      hypertensives with controlled blood pressure has increased from 10% in 1986 to
      13% in 1995, and cerebrovascular mortality has steadily decreased.

PMID- 9657644
TI  - Change in cerebral glucose metabolism during limbic seizures elicited from
      lateral septal nucleus.
AB  - The roles of the amygdala and hippocampus have been extensively studied in limbic
      seizures. Although the septal nuclei have a close connection to the hippocampus
      and affect emotional behavior, the effect on limbic seizures is still unclear. We
      have reported that characteristic sham-rage seizures were observed in cats, by
      administering a local injection of kainic acid (KA) into the lateral septal
      nucleus (LSN). This study investigated the electrophysiological features of KA
      induced septal seizures in rats and analyzed the process in relation to the
      cerebral glucose metabolism using [14C]deoxyglucose autoradiography. On EEG,
      epileptic discharge eliciting from the LSN rapidly propagated to the hippocampus
      and the amygdala. Behavioral change was similar to that in limbic seizures
      induced by intraamygdaloid KA. Sham-rage seizure was not observed in rats.
      However, the local cerebral glucose metabolism during the seizures increased not
      only in the limbic structures including the LSN but also in the hypothalamus and
      periaqueductal grey matter of the midbrain. The findings were distinctive of
      septal seizures as compared with amygdaloid seizures. The results suggested that
      sham-rage seizures in cats might be caused by a secondary epileptogenic
      excitation in the hypothalamus or periaqueductal grey matter of the midbrain. The
      septal nuclei may play an important role in emotional behavior associated with
      limbic seizures even if there is a species difference in its function.

PMID- 9657645
TI  - Intracortical functional heterogeneity in area striate during penicillin-induced
      spikes in rabbits.
AB  - The generation and spread of epileptiform activity within the cortex depend on
      the functional and anatomical relationships between the focus and its surrounding
      area. These processes are not completely understood. Thus intracortical current
      source-density analysis (CSD) was performed in six rabbits in order to
      investigate this functional relationship. Electric potential was measured
      perpendicular to the cortical surface by means of two 16-channel probes, and CSD
      was calculated within the focus and at various distances of up to 5 mm. The
      cortical areas surrounding the focus could be subdivided into three regions. The
      region up to 3 mm from the focus showed similar activity but beyond 4.5 mm no
      characteristic functional relationship was found with regard to the epileptiform
      events within the focus. Within the region 3.5-4.5 mm, however, mainly
      supragranular cells seem to contribute to the electric potential measured at the
      cortical surface and within the extracellular space. They were activated
      simultaneously with the initiation of focal spike generation. Taking into account
      the distribution of the electric potential and the results of CSD analysis, these
      cells seem mainly involved in the inhibition of the horizontal spread of spike
      activity.

PMID- 9657646
TI  - Histaminergic mechanisms in amygdaloid-kindled seizures in rats.
AB  - The present study was undertaken to clarify the role of histaminergic neuron
      system on amygdaloid kindled seizures in rats. A significant decrease in
      histamine contents in the amygdala was observed after development of amygdaloid
      kindling. Histidine and metoprine inhibited amygdaloid kindled seizures at doses
      causing an increase in histamine contents of the brain. H1-antagonists
      (diphenhydramine and chlorpheniramine) attenuated histidine-induced inhibition of
      amygdaloid kindled seizures, however no significant antagonism was observed with
      H2-antagonists (zolantidine and ranitidine). The development of amygdaloid
      kindling was retarded by repeated administration of histidine. These findings
      suggest that histaminergic mechanisms play a suppressive role in amygdaloid
      kindled seizures through histamine H1-receptors.

PMID- 9657647
TI  - Evaluation of the anticonvulsant profile of progesterone in male amygdala-kindled
      rats.
AB  - While there is clinical evidence that progesterone has anticonvulsant activity in
      women with complex partial seizures, previous studies on the anticonvulsant
      effect of progesterone in experimental animal models are inconclusive. Moreover,
      the effect of progesterone on seizure parameters in fully amygdala-kindled rats
      which best resemble complex partial seizures has not been evaluated. Therefore,
      in the present work the anticonvulsant effect of progesterone at doses of 10, 30,
      60 and 75 mg/kg in fully amygdala-kindled male rats was studied. Only at the high
      and sedative dose of 75 mg/kg, progesterone suppressed behavioral seizures and
      afterdischarges elicited 10 min after intraperitoneal (i.p.) administration.
      Pretreatment with the progesterone antagonist, 17beta-hydroxy-11beta-(4
      dimethylaminophenyl)-17alpha-(prop- 1-ynyl)-estra-4,9-dien-3-one (RU 38486) at
      the dose of 3 mg/kg did not inhibit the anticonvulsant activity of progesterone,
      while pretreatment with the GABA(A) receptor antagonist, bicuculline (2 mg/kg)
      blocked the anticonvulsant effect of progesterone. Neither RU 38486 nor
      bicuculline had any effect on the seizure parameters. These findings suggest that
      only at large and sedative doses, progesterone has some anticonvulsant activity
      in male amygdala-kindled rats which may be partly mediated via the GABA(A)
      receptor complex interaction.

PMID- 9657648
TI  - Acute heat stress model of seizures in weanling rats: influence of prototypic
      anti-seizure compounds.
AB  - The present study tested the therapeutic potential for prototype anti-epilepsy
      drugs using an animal model of infantile febrile seizures. The model consisted of
      immersion of weanling rats (21 days old) in a 45 degrees C water bath for a
      maximum of 4 min (four exposures over a 2 week period) and observing for the
      progression to stage-5 seizures. All compounds were administered orally at the
      respective ED50 for prevention of seizures in the maximal electroshock (MES)
      test. Clonazepam effectively lowered the score for seizure grade, shortened the
      duration of seizures, as well as reduced the number of animals experiencing
      seizures during three of the four testing periods. MK801 reduced both the maximum
      seizure grade, and the number of animals experiencing seizures during sessions
      two and three. However, the dose of MK801 caused behavioral side effects.
      Valproate actively decreased seizure grade, while it modestly acted to attenuate
      seizure duration, extended the time to seizure onset, and reduced the number of
      animals experiencing seizures on testing day 1. Remacemide hydrochloride and
      phenobarbital were not effective. The method appears useful for evaluating the
      potential of agents to prevent acute febrile seizures.

PMID- 9657649
TI  - Frontal versus transcorneal stimulation to induce maximal electroshock seizures
      or kindling in mice and rats.
AB  - Frontal stimulation, i.e. electrical stimulation where electrodes are pressed on
      the skin of the intact frontal skull of mice or rats, may represent a more humane
      alternative to the widely used transcorneal stimulation to induce electroshock
      seizures. The aim of this work was to directly compare transcorneal and frontal
      stimulation in eliciting maximal electroshock-induced seizures (MES) in mice and
      the anticonvulsant effect of carbamazepine (CBZ) and phenytoin (PHT) on thus
      produced seizures. In addition, we stimulated mice and rats repeatedly via
      transcorneal and frontal electrodes to see whether kindling is produced by this
      procedure. Two electroshock tests were used in mice, i.e. maximal electroshock
      seizure threshold (MEST) test and MES generated by supramaximal stimulation (50
      mA). Frontal stimulation resulted in lower convulsive threshold than in the case
      of corneal stimulation. Both CBZ and PHT produced dose-dependent increases in
      seizure threshold for both sites of stimulation, i.e. transcorneal and frontal.
      As regards type of electrodes, higher doses of PHT were required to increase
      seizure threshold in the case of frontal than transcorneal stimulation.
      Supramaximal stimulation (50 mA) yielded comparable ED50 values regardless of the
      site of stimulation. Furthermore, once-daily stimulation of mice, regardless of
      the placement of electrodes, did not induce any changes in convulsive threshold.
      We also attempted to kindle mice and rats via corneal and frontal electrodes by
      repetitive electrical stimulation using currents which initially did not produce
      generalized clonic seizures. Mice were stimulated once daily for 2 s with 3 mA
      (corneal electrodes) or 2 mA (frontal electrodes) and rats were stimulated twice
      daily for 4 s at 8 mA (corneal electrodes) or 5 mA (frontal electrodes). With
      corneal stimulation in rats there was a clear progression of kindling development
      which was not the same in nature when compared with corneally-stimulated mice.
      Frontal stimulation did not produce kindling. Moreover, corneal stimulation was
      better tolerated by rats, while in mice high mortality was seen after either
      method of current delivery. Our data indicate that frontal electrodes can be used
      as an alternative to transcorneal stimulation to produce MES by supramaximal or
      threshold current intensities as screening procedures in antiepileptic drug (AED)
      development. Nevertheless, this type of stimulation cannot be used to produce
      minimal electroshock seizures and seems not to be useful to produce kindling in
      rats and mice.

PMID- 9657650
TI  - The relationship between seizure frequency, seizure type and quality of life:
      findings from three European countries.
AB  - Understanding the relationship between seizure frequency, seizure type and scores
      obtained from quality of life (QOL) measures is important if the incorporation of
      QOL measures into epilepsy clinical trials is to become standard practice. There
      is also a need to consider cross-cultural differences obtained from QOL measures,
      particularly in the context of multicentre international trials. In this study,
      300 patients recruited from UK, Germany and France completed the Functional
      Status Questionnaire (FSQ); information about patients' clinical and demographic
      status was also collected. Results from the study highlighted that seizure type
      and seizure frequency, as well as country of origin, were significant predictors
      of scores on the FSQ. It is important to measure the effect of seizure type, not
      just seizure frequency, on QOL when testing for differences between antiepileptic
      therapies in the context of clinical trials.

PMID- 9657651
TI  - Hyponatremia induced by oxcarbazepine in children.
AB  - We report the case of a 12-year-old girl with severe clinically relevant
      hyponatremia (118 mmol/l) and hypochloremia (81 mmol/l) during treatment with
      oxcarbazepine (OCBZ). The adverse effects were rapidly reversible after
      discontinuation of OCBZ and did not occur when exposed to carbamazepine. We
      reviewed the charts of 48 patients who received OCBZ as in-patients in our
      epilepsy centre and found hyponatremia in nine and hypochloremia in four. The
      mean sodium level of all patients was 139 mmol/l (range 118-150 mmol/l). We did
      not see any correlation between sodium or chloride levels and dose of OCBZ or
      blood serum level of the active metabolite 10-OH-carbazepine. We emphasize that
      children are at risk of developing electrolyte disturbances during treatment with
      OCBZ and thus the level of at least sodium should be monitored in those patients.

PMID- 9657652
TI  - High incidence of epilepsy related to onchocerciasis in West Uganda.
AB  - The incidence of epilepsy was assessed in an onchocerciasis endemic area in West
      Uganda over a period of 4 years. A high overall crude incidence rate of 215 per
      100000 person-years was found (age-adjusted: 156 per 100000 person-years) and the
      incidence in zones of high onchocerciasis endemicity was significantly higher
      than in low endemic zones (age adjusted rates: 232 per 100000 person-years versus
      77 per 100000 person-years; Yates corrected chi2: P < 0.01). The data constitute
      a baseline for an ongoing intervention study on the effects of onchocerciasis
      control on epilepsy incidence in the study area. If a causal relationship between
      onchocerciasis and epilepsy can be confirmed, this would have significant
      implications for the concept of morbidity due to onchocerciasis and for the
      prevention of epilepsy in the endemic areas.

PMID- 9657653
TI  - Central sleep apnoea and heart failure (part II).
AB  - Central sleep apnoea (CSA) in congestive heart failure is sleep state dependent
      and occurs typically in stages I and II of non-REM sleep. The pre-requisites are
      hypocapnia and some prolongation of the circulation time. It is not certain
      whether abnormalities in after-discharge activity in the brainstem are also
      important. The presence of CSA in patients with left ventricular dysfunction is a
      poor prognostic sign and associated with a higher mortality in that group
      compared to age, sex and ejection fraction matched patients with congestive
      cardiac failure alone. It is reasonable to speculate that the CSA causes an
      increase in sympathetic nervous system activity which would maintain afterload at
      a high level or tend to increase it with time. The application of a high
      afterload to an impaired left ventricle leads over time to a further reduction in
      ejection fraction. From other studies, particularly ACE inhibitor studies, it is
      known that ejection fraction and prognosis are almost linearly related. It could
      therefore be said that once CSA has developed it may lead to a vicious circle of
      increasing afterload and further reduction in ejection fraction, causing
      worsening CSA and further increases in afterload. A number of treatments have
      been shown to be of benefit: supplemental nocturnal oxygen therapy, acetazolamide
      and nasal CPAP therapy have all been shown to reduce CSA. In addition nasal
      continuous positive airways pressure (CPAP) has been shown by two groups in
      Canada to also improve ejection fraction. The beneficial effects on ejection
      fraction in particular, persist after the treatment has been withdrawn, which
      suggests either remodelling of the left ventricular musculature or a resetting of
      the baseline sympathetic nervous system activity. The impressive increase in
      ejection fraction due to three months nasal CPAP therapy in one study (an average
      35% increase) is both dramatic and exciting for the future. It is reasonable to
      expect improvement in prognosis for patients with CCF whose ejection fraction
      rises with CPAP treatment. Finally, only a limited number of studies have been
      published. Unfortunately the impressive results from Canada have not yet been
      reproduced in other centres around the world.

PMID- 9657654
TI  - The effect of inhaled budesonide on the diurnal variation in airway mechanics,
      airway responsiveness and serum neutrophil chemotactic activity in Asian patients
      with predominant nocturnal asthma.
AB  - The effectiveness of inhaled corticosteroids in the control of daytime symptoms
      in asthma is well established, but the specific use against nocturnal asthma has
      not been systematically studied in Asian patients. This study examined the effect
      of treatment with inhaled budesonide on the nocturnal variation in measurements
      of airway calibre, bronchial hyperresponsiveness to inhaled histamine and
      circulating neutrophil chemotactic activity in Asian patients with nocturnal
      asthma. Thirty patients, with nocturnal asthma, were randomized into a 2-month,
      double-blind, parallel group study. Twice as many subjects were allocated to the
      group who received two consecutive months of inhaled budesonide 1600 microg daily
      as to the group who received placebo followed by budesonide. Spirometry, lung
      mechanics, bronchial hyperresponsiveness and serum neutrophil chemotactic factor
      (NCA) were measured at 16.00 h, 22.00 h and at 04.00 h on 3 days and nights, 4
      weeks apart before and after either placebo or budesonide. The combined
      measurements for the two groups at 04.00 h before and after treatment with
      budesonide were: forced expiratory volume in 1 s (FEV1) mean (SEM) litres 1.34
      (0.17) before, 2.00 (0.19) after; thoracic gas volume (TGV) litres 3.05 (0.32)
      before, 2.25 (0.14) after; specific airway conductance (sGaw) (cmH20.0 sec)(-1)
      0.39 (0.07) before, 1.16 (0.17) after; PD20 microg geometric mean 1.16 before,
      44.74 after; neutrophil chemotactic activity (NCA) in units of graduations of
      migration 98.8 (4.2) before, 101 (14.2) after. The data showed that short and
      intermediate term high dose inhaled budesonide is an effective specific treatment
      for nocturnal asthma in Asian patients, resulting in marked improvements in
      symptoms and in lung mechanics, and reductions in the diurnal variations in
      bronchial hyperresponsiveness, before any change could be demonstrated in a
      circulating marker of airway inflammation.

PMID- 9657655
TI  - Simultaneous continuous 13C, 12C analysis of expired gas in the 13C breath test.
AB  - The 13C breath test is a method of clarifying the metabolism of loaded substances
      by administering 13C-labelled materials and calculating the 13CO2 and 12CO2 ratio
      (13C/12C isotope ratio) in the expired gas. The materials are metabolized and
      expelled in the expired gas. Because simultaneous continuous measurement of 13CO2
      and 12CO2 in expired gas has been difficult up to the present, respective expired
      gases, including dead space before and after administration, have been sampled to
      separate sampling bags and 13C/12C has been measured in the bags and changed
      fraction of 13C/12C after administration (delta) has been used to judge the
      metabolic process. This method is affected by the contamination of the dead space
      gas. In the present study, in order to exclude the dead space effect,
      simultaneous continuous analysis of 12CO2 and 13CO2 of expired gas identifying
      alveolar gas was applied to the 13C-urea breath test in addition to the
      conventional sampling bag method. Both isotope detectors were attached to a mass
      spectrometer. Fifty-six cases receiving stomach health check-ups for Helicobacter
      pylori were examined. Delta was calculated in the bag or in phase III of
      continuous gas measurement. Because the bag contains dead space, delta was
      reduced and sensitivity and specificity with reference to gastric fluoroscopy or
      Helicobacter pylori IgG antibody were reduced. Decreasing the dead space
      contamination is important in reducing the measurement error in the 13C breath
      test and simultaneous continuous measurement is a good tool for this purpose.

PMID- 9657656
TI  - Reversible airway obstruction in rheumatic mitral valve disease.
AB  - Lung function was studied in 24 patients with advanced mitral stenosis scheduled
      for mitral valve replacement (MVR), and revealed an obstructive ventilatory
      pattern. Forty per cent of the patients had a forced expiratory volume in 1 s
      (FEV1)<60% of that predicted in the preoperative period. Twenty-five per cent of
      those operated upon showed a similar pattern up to 110 weeks postoperatively. A
      blind study of the effect of placebo and beta2 agonist (salbutamol) inhalation
      was performed preoperatively and 6 months postoperatively, to evaluate the
      reversibility of airflow obstruction in these patients, flow volume curve and
      body plethysmographic measurement of airway resistance (Rex) and intrathoracic
      gas volume (VTG). Patients in the pre and postoperative period showed a
      significant difference between the placebo and the beta2 agonist responses for
      FEV1, FEV1 as percentage of FVC (FEV1% FVC), peak expiratory flow rate (PEFR),
      flow rate of 50% of expiratory vital capacity (Vmax50), Rex and VTG (P<0.001). We
      conclude that salbutamol inhalation improves obstructive impairment in patients
      with MVR pre- and postoperatively.

PMID- 9657657
TI  - Computed tomographic findings of environmental asbestos-related malignant pleural
      mesothelioma.
AB  - Malignant pleural mesothelioma (MPM) is not an infrequent fatal neoplasm. It is
      endemically present in some regions of Turkey due to its aetiological
      relationship to exposure to environmental fibrous minerals. The aim of this study
      was to determine the thorax computed tomographic (CT) features of environmental
      asbestos-related MPM. In this study, we examined retrospectively the CT scans of
      46 untreated patients with pathological diagnosis of environmental asbestos
      related MPM among 151 patients with malignant pleural mesothelioma in the Izmir
      Chest Disease and Surgery Hospital. The CT scans were interpreted by consultation
      of four observers. Malignant pleural mesothelioma was unilateral in 45 (97.2%) of
      the patients. Pleural effusions were found in 42 (91%) of the patients, pleural
      calcifications in 12 (26%), contracted hemithorax in 14 (30%), interlobar fissure
      involvement in 25 (54%) and mediastinal pleural involvement in 26 (57%). A
      contracted hemithorax was significantly correlated with pleural rind
      configuration. Pleural thickenings were found in 45 (99%) of the patients.
      Pleural thickenings were in the form of nodularity in 10 (22%) cases, regular in
      12 (27%) cases, as a focal mass in 3 (7%) cases and as a pleural rind in 20 (44%)
      cases. Pleural thickening was greater than 1 cm in 32 (71%) cases. The most
      common CT findings in our series were unilateral circumferential pleural
      thickening, nodular pleural thickening, pleural thickening greater than 1 cm and
      mediastinal pleural involvement. Generally, pleural effusion was accompanied by
      this. There was interlobar fissure involvement in half of the patients. There was
      no pathognomonic CT finding in environmental asbestos-related MPM. But CT was
      useful in suggesting the diagnosis of malignant pleural disease in the cases with
      MPM.

PMID- 9657658
TI  - Angiotensin converting enzyme inhibitor cough: lessons from heart-lung
      transplantation.
AB  - Coughing is a frequent side-effect of angiotensin converting enzyme (ACE)
      inhibitors. Its pathogenesis is thought to be related to the local accumulation
      of tachykinins although the role of extrinsic cholinergic pathways is unclear.
      The development of an ACE inhibitor induced cough in two patients who have
      undergone heart-lung transplantation and in whom cholinergic pathways remain
      denervated supports the hypothesis of a 'local' mechanism.

PMID- 9657659
TI  - Sarcoidosis induced by interferon therapy for chronic myelogenous leukaemia.
AB  - A 31-year-old male was diagnosed as having chronic myelogenous leukaemia and has
      been treated with hydroxyurea and interferon-alpha since February 1995. After 16
      months, he complained of low-grade fever and a cough. Bilateral hilar lymph node
      enlargement was detected on the chest X-ray film and multiple subcutaneous
      erythematous nodules appeared. A skin biopsy revealed subcutaneous sarcoid
      granuloma. Two months after the cessation of interferon therapy, the subcutaneous
      nodules and the hilar lymph node enlargement resolved. It is possible that
      continuous interferon administration can promote granuloma formation in
      sarcoidosis by activating T cells and macrophages.

PMID- 9657660
TI  - Molecular studies of bronchial asthma, sarcoidosis and angiotensin converting
      enzyme inhibitor-induced cough.
AB  - The role of genetic factors was reviewed with respect to the pathophysiology of
      bronchial asthma, sarcoidosis and cough induced by angiotensin converting enzyme
      (ACE) inhibitor administration. The so-called 'atopy gene' in 11q13 is not linked
      to atopy but is associated with serum IgE levels. The beta2-adrenergic receptor
      gene on 5q32-33 was found to have polymorphism by Ban I and to be related to
      beta2-receptor function; a defect of a 2.3 kb allele is related to lowered
      sensitivity to beta2-agonists. This defect is also related to higher prevalence
      on non-atopic bronchial asthma. The occurrence of amino acid mutation (Arg16 to
      Gly) of beta2-receptors was lower and Gln27 to Glu mutation is extremely rare in
      the Japanese population compared with Caucasians. There is polymorphism of ACE
      genotypes among normal subjects and patients with sarcoidosis, II, ID and DD. The
      genotype is a significant determinant of serum ACE activity and may determine the
      prognosis of sarcoid patients. Genotype II has a higher incidence of coughing
      induced by ACE inhibitors.

PMID- 9657661
TI  - Management of non-small cell lung cancer according to staging--an update.
AB  - The treatment of non-small cell lung cancer (NSCLC) depends on staging based on
      tumour (T), nodal (N) and metastasis (M) descriptors. Stages I and II tumours are
      potentially curable with surgery alone. Stage IIIA T3 tumours are also
      potentially operable. Preoperative chemotherapy appears promising in downstaging
      stage IIIA disease to enable surgical resection. Recent meta-analyses did not
      support the use of postoperative chemotherapy for stages I, II and IIIA diseases,
      but were supportive of the use of cisplatin-based chemotherapy in stage IIIA N2
      disease (+ radiotherapy), stage IIIB disease (+ radiotherapy) and in metastatic
      stage IV disease in improving survival. New chemotherapy agents available over
      the past few years would further improve the efficacy of chemotherapy in NSCLC.

PMID- 9657662
TI  - Tumour-infiltrating lymphocytes in non-small cell lung cancer are activated T
      lymphocytes.
AB  - This study was carried out in order to investigate the local immune reaction of
      tumour-infiltrating lymphocytes (TILs) in the primary tumours of non-small cell
      lung carcinomas. Thirty non-small cell lung cancer (NSCLC) patients were
      included. The tumour tissue was taken at thoracotomy and monocellular suspension
      of the tumour was obtained by mechanical disaggregation. Dual-coloured flow
      cytometric analysis of TILs and their corresponding peripheral blood lymphocytes
      (PBLs) was performed. Tumour-infiltrating lymphocytes contained significantly
      higher proportions of CD3(+) T lymphocytes and CD8(+) T lymphocytes than the
      corresponding PBLs (82.0%+/-13.9% vs 66.3%+/-10.6% for CD3, P<0.001; 39.0%+/
      18.4% vs 26.4%+/-5.2% for CD8, P<0.001). Tumour-infiltrating lymphocytes
      contained significantly higher proportions of activated memory lymphocytes than
      PBLs did (9.8%+/-8.6% vs 1.3%+/-1.5% for CD25, P<0.001; 40.5%+/-30.2% vs 10.2%+/
      14.8% for CD71, P<0.001; 75.5%+/-11.9% vs 28.6%+/-9.8% for HLA-DR, P<0.001).
      These findings were also found in both CD4(+) TILs and CD8(+) TILs. The TILs of
      NSCLC contained higher proportions of T lymphocytes and CD8(+) lymphocytes than
      their corresponding peripheral bloods. The proportions of activated memory
      lymphocytes were also significantly higher in the TILs, both in CD4(+) TILs and
      CD8(+) TILs, than the corresponding PBLs.

PMID- 9657663
TI  - Postnatal development of urea synthesis capacity in preterm infants with
      intrauterine growth retardation.
AB  - The postnatal development of the urea-synthesizing capacity was studied in 21
      preterm infants with intrauterine growth retardation (IUGR) and compared with
      results found in 12 infants without IUGR as controls. The urea-synthesizing
      capacity was estimated by the ratio Q of 15N abundance of ammonia and urea in 6
      hour urine samples collected after enteral administration of 3 mg [15N]H4Cl/kg
      body weight. The measurements were performed on the first day when a protein
      intake of 3.0-3.5 g/kg/day and an energy intake of 120 kcal/kg/day were tolerated
      (study day 1: postnatal 14-21 days) and on the day of discharge from the hospital
      (study day 2: postnatal age 39-56 days). The group of infants with IUGR was
      subdivided in one group of infants who developed catch-up growth (n = 12) and one
      group who did not demonstrate catch-up growth (n = 9). On study day 1, the Q
      values of the IUGR infants without catch-up growth were significantly higher than
      those of the IUGR infants with catch-up growth (13.4 +/- 2.3 vs. 9.2 +/- 2.2) or
      of the control infants without IUGR. During the time period from study day 1 to
      study day 2 the Q values of the IUGR infants with catch-up growth decreased
      significantly (9.2 +/- 2.2 vs. 4.8 +/- 2.0; p < 0.001) and were in the range of
      the control infants without IUGR. In contrast, the Q values of the IUGR infants
      without catch-up growth did not significantly change during the study period
      (13.4 +/- 2.3 vs. 11.3 +/- 2.8; p = 0.097). On both study days there was a
      significant correlation between the Q values and the degree of IUGR (study day 1:
      r = 0.652, p < 0.01; study day 2: r = 0.842, p < 0.001). The data indicate that
      the urea-synthesizing capacity of preterm infants increases during early
      postnatal life and that severe IUGR may impair this development. Metabolic
      investigations using urea as marker for evaluation of optimal quantity or quality
      of dietary proteins should carefully be interpreted when infants with severe IUGR
      are studied.

PMID- 9657664
TI  - Epidemiology of neonatal acute respiratory disorders. A multicenter study on
      incidence and fatality rates of neonatal acute respiratory disorders according to
      gestational age, maternal age, pregnancy complications and type of delivery.
      Italian Group of Neonatal Pneumology.
AB  - A prospective 3-month survey of neonatal respiratory disorders in 17,192 Italian
      infants born in 65 hospitals, located in 17 Italian regions representative of
      northern, central and southern Italy, was performed to evaluate the incidence of
      neonatal acute respiratory disorders and their risk factors. The prematurity rate
      was 7.3%, while the extremely low birth weight (< 1,000 g) and very low birth
      weight (< 1,500 g) rates were 0.58% and 0.99%, respectively. Four hundred and
      ninety-one infants (2.8%) developed respiratory signs. Lethality or specific
      fatality rate (SFR) for acute respiratory disorders with regard to the overall
      study population was 0.45%. The male/female ratio of affected infants was 1.3:1.
      Among affected newborns the case fatality rate (CFR) for respiratory disorders
      was 15.88% (78/491) and was higher in males than in females (2:1), in infants
      with a gestational age of < or = 28 weeks (60%) and birth weights of < 1,000 g
      (50%). Moreover, the SFR was higher (p < 0.05) in the infants of mothers older
      than 34 years. SFR was 3.0% in intrauterine growth-retarded infants, 3.6% in the
      first twin and 3.2% in the second twin. An Apgar score of < or = 3 at 5 min was
      strongly related to the incidence of respiratory disorders (47.1%). The antenatal
      prevention of neonatal respiratory distress syndrome with maternal corticosteroid
      treatment was performed in 84% of newborns (< 32 weeks) with respiratory problems
      in northern Italy, and about 25% and 38% in central and southern Italy,
      respectively. The CFR was double in southern Italy as compared with northern and
      central Italy. Prematurity, low birth weight and a low Apgar score (< or = 3) at
      1 and 5 min as well as a maternal age of > 34 years are risk factors for acute
      respiratory disorders.

PMID- 9657665
TI  - Different patterns of sighs in neonates and young infants.
AB  - To examine the prevalence and clinical assessment of sighs in neonates, we
      observed three different patterns of sighs: (A) sighs in the absence of apneic
      pause; (B) sighs with instantly following apneic pause >2 s, and (C) sighs with
      apneic pause >2 s following 1-3 normal breaths. We investigated preterm and term
      infants with 12 h nocturnal polygraphic recording. Sighs were more frequent in
      preterm than in term infants and more so during REM sleep than non-REM sleep. The
      part of sighs B of total number of sighs increased with gestational age. During
      REM sleep sighs without apnea were predominant, whereas apnea-associated sighs
      were mainly found during non-REM sleep.

PMID- 9657666
TI  - Nitric oxide modulates premature renal circulation in hypoxic newborn piglets.
AB  - We studied the role of nitric oxide (NO) on the regulation of blood flow in the
      immature kidney during hypoxia, resuscitation and the recovery period using the
      NO inhibitor N(omega)-nitro-L-arginine (L-NNA) in a newborn piglet model, and the
      possibility of urinary cGMP as an index of renal function. After administration
      of L-NNA, the blood flow in both the cortex and medulla significantly decreased,
      indicating that NO is constantly released to maintain renal circulation. During
      hypoxia, the renal blood flow fell remarkably, and there were no differences
      between the control and L-NNA groups. During the post-resuscitation period, the
      recovery of renal blood flow was significantly suppressed in L-NNA
      administration, and it was speculated that NO might be an important factor for
      recovery of circulation from vasoconstriction due to hypoxemia. Urinary cGMP/cr
      was significantly increased on recovery from hypoxemia and was suppressed by L
      NNA administration. This result suggested that the change in cGMP/cr represents
      renal blood flow change. We conclude that NO may play an important role in
      maintaining basal hemodynamics, and may also be a crucial factor for recovery
      from post-hypoxic vasoconstriction in premature kidneys. Urinary cGMP/cr might
      serve as one of the indices for assessment of premature renal circulation.

PMID- 9657667
TI  - Effect of dietary n-3 fatty acids on hypoxia-induced necrotizing enterocolitis in
      young mice. n-3 fatty acids alter platelet-activating factor and leukotriene B4
      production in the intestine.
AB  - Necrotizing entercolitis (NEC) is an important neonatal disease with a high
      mortality rate. Inflammatory mediators, such as mainly platelet-activating factor
      (PAF), leukotrienes (LT) and tumor necrosis factor play an important role in the
      genesis of NEC. Diets in omega-3 (n-3) fatty acids appear to have an
      antiinflammatory effect, which is thought to be due to decreased active
      prostaglandins and leukotrienes production after incorporation of these fatty
      acids into cell membrane phospholipids. We investigated the protective effect of
      fish oil (source of n-3 fatty acids) on hypoxia-induced model of NEC. Young mice
      were divided into three groups; group 1 mice were fed standard chow (n-3 fatty
      acids-free), group 2 was fed a chow supplemented by 10% fish oil for 4 weeks.
      Group 3 mice served as control. We examined the intestinal lesions by light
      microscopy and measured intestinal tissue PAF and LB4 levels in hypoxia-induced
      model of NEC. Significantly increased intestinal PAF and LTB4 levels were found
      in group 1 mice when compared to group 2 and group 3 mice. The histopathology of
      the intestinal lesions in group 1 animals was characteristic of ischemic injury.
      In the n-3 fatty acids-supplemented animals these lesions were milder. The
      present study shows that endogenously released PAF and LTB4 play an important
      role in mediating hypoxia-induced intestinal necrosis. The present study also
      suggests that dietary supplementation with n-3 fatty acids suppress intestinal
      PAF and LTB4 generation in hypoxia-induced bowel necrosis. The intestinal
      protective effect of n-3 fatty acids in an experimental model of NEC may open new
      insight into the treatment and prevention of NEC in neonates.

PMID- 9657668
TI  - Pharmacodynamic effects and pharmacokinetic profile of continuous infusion
      fentanyl in newborn piglets.
AB  - The objective of this study was to determine hemodynamic effects and
      pharmacokinetic profiles of fentanyl with continuous infusion in 1- to 3-day-old
      newborn piglets. The piglets (n = 6) were administered a loading dose of fentanyl
      at 30 microg/kg i.v. over 15 min followed by a continuous i.v. infusion at 10
      microg/kg/h for 6 h. The control group (n = 8) received equivalent volume bolus
      and infusion of 5% dextrose. Blood samples were obtained serially from systemic
      circulation and sagittal sinus vein for measurement of plasma fentanyl, pH and
      blood gases. Plasma fentanyl achieved steady state levels by 30 min of infusion
      both in the systemic (202.7 +/- 39.1 ng/ml) and sagittal sinus vein (136.7 +/-
      20.7 ng/ml). Fentanyl caused a transient increase in respiratory rate at 2 h.
      Heart rate was significantly elevated at 30 min and 6 h during infusion but
      systemic and sagittal sinus vein blood pressure remained unchanged. Systemic and
      sagittal sinus vein PO2 were significantly decreased from 2 through 6 h of
      infusion. Compared to the control group, there was a 56% (p < 0.01) decrease in
      sagittal sinus vein O2 content at 30 min of infusion, an effect which lasted up
      to 6 h (47%, p < 0.01). Fractional O2 extraction by the brain increased
      significantly at 30 min (26%, p < 0.01) and remained elevated throughout the
      infusion time (22%, p < 0.05 at 6 h). Brain fractional O2 extraction increased as
      a function of brain fractional fentanyl extraction (r2 = 0.40, p < 0.001). Mean
      clearance was estimated as 56.2 +/- 13.7 ml/kg/h (range 43.5-76.9 ml/kg/h), mean
      volume of distribution at steady state was 1.29 +/- 0.6 liters/kg (range 0.78
      2.15 liters/kg) and the mean half-life was 15.7 +/- 5.7 h (range 9.4-22.5 h).
      These data suggest that increased systemic oxygen may be necessary to maintain
      normal cerebral oxygen extraction during fentanyl anesthesia/analgesia.

PMID- 9657669
TI  - Responses to stress and novelty in adult rats born vaginally, by cesarean section
      or by cesarean section with acute anoxia.
AB  - The aim of this study was to test the hypothesis that alterations in birth
      conditions, specifically vaginal birth vs. birth by Cesarean section (C-section)
      vs. birth by C-section with an added period of acute global anoxia, produces long
      term differences in behavioral responses to stress or novelty in the rat at
      adulthood. In comparison to animals born by rapid C-section alone, animals born
      by C-section with 10 or 15 min of added anoxia were significantly more immobile
      during forced swim stress administered for 6 trials over several weeks. In a step
      down passive avoidance task, there were no group differences in acquisition or
      retention of the avoidance response. However, when initially placed in the
      passive avoidance apparatus before delivery of shock, animals born by C-section
      with 15 min of anoxia required significantly more pretrials to step down from the
      wooden platform, than did vaginally born or C-sectioned animals. No group
      differences were observed on measures of exploratory behavior in an elevated plus
      maze or of approach behavior either to food or to a novel object in an open
      field. These findings suggest that birth conditions which include a degree of
      perinatal hypoxia can contribute to variability in selective responses to stress
      and novelty in the adult rat.

PMID- 9657670
TI  - Developmental changes in the calcium sensitivity of rabbit cranial arteries.
AB  - The present experiments examine developmental changes in cerebrovascular Ca2+
      sensitivity. Common carotid (COM), basilar (BAS) and femoral (FA) arteries from
      adult (n = 16), 8- to 9-day-old (n = 15) and 24- to 25-day-old rabbits (n = 12)
      were denuded of the endothelium and permeabilized with beta-escin. Bath calcium
      concentrations were controlled via EGTA-Ca2+ buffer solutions. Adult pCa-force
      relations were right-shifted relative to those of 8- to 9-day-old rabbits but
      were similar to those of 24- to 25-day-olds. Adult pD2 (-log ED50) values for
      Ca2+ averaged 6.36 +/- 0.03 (COM), 6.77 +/- 0.04 (BAS) and 6.40 +/- 0.04 (FA).
      Corresponding 8- to 9-day-old values were 6.85 +/- 0.03, 7.08 +/- 0.08 and 6.76
      +/- 0.05. In all arteries studied, the addition of 5-hydroxytryptamine (5-HT)
      subsequent to contraction by a constant submaximal (EC30) concentration of Ca2+
      produced a dose-dependent and GDP3S-sensitive increase in tension attributable to
      an increase in Ca2+ sensitivity. The magnitudes of 5-HT-induced increases in Ca2+
      sensitivity were significantly greatest in 8- to 9-day-old rabbits, intermediate
      in 24- to 25-day-old rabbits, and least in adults. GTPgammaS mimicked the effects
      of 5-HT and prevented further increases in Ca2+ sensitivity induced by 5-HT in
      all arteries from all age groups. GDPbetaS completely reversed all effects of 5
      HT on Ca2+ sensitivity. From these data we conclude that baseline Ca2+
      sensitivity is elevated in newborn relative to adult rabbits, at least in
      femoral, common carotid and basilar arteries. In these arteries, 5-HT can
      increase Ca2+ sensitivity via a G-protein-dependent mechanism which is more
      effective in neonatal than adult arteries. These effects of maturation on
      vascular Ca2+ sensitivity may play an important role in developmental changes in
      vascular reactivity.

PMID- 9657671
TI  - Biotin plasma levels of the human fetus.
AB  - Biotin is an important vitamin for cellular function and growth and, therefore,
      essential for fetal development. The fetus is exclusively dependent on maternal
      biotin supply. Since biotin is not produced within the body, maternal biotin
      levels depend on dietary intake. In order to investigate the biotin status of the
      human fetus, we measured the plasma biotin levels in 15 pregnant women and their
      fetuses who underwent amniocentesis and fetal blood sampling at 18-24 weeks of
      gestation for prenatal diagnosis of thalassemia. Maternal biotin was found to be
      131 +/- (SD) 102 ng/l and fetal biotin 784 +/- 327 ng/l (p < 0.0001). Our
      findings are indicative of an active transport mechanism of biotin through the
      placenta in favor of the fetus.

PMID- 9657672
TI  - Deoxyribose phosphate excision by the N-terminal domain of the polymerase beta:
      the mechanism revisited.
AB  - DNA polymerase beta (Pol beta) is one of the key enzymes in the base excision
      repair pathway. The amino-terminal 8 kDa domain of Pol beta has an activity for
      excising a 5'-deoxyribose phosphate (dRP) group from preincised
      apurine/apyrimidine (AP) sites. Recent biochemical studies have identified the
      catalytic center of the 8 kDa domain and provided new insight into the mechanism
      of DNA repair by DNA polymerase beta. By incorporating both structural and
      biochemical data, we present here a reaction mechanism for the 5'-dRP excision
      activity of the 8 kDa domain. This mechanism focuses on a catalytic groove near
      the helix-hairpin-helix (HhH) motif of the 8 kDa domain. Our model shows that the
      dRP group of the AP site can be stabilized in the catalytic groove through
      extensive interactions with the residues of the groove and be positioned close to
      the active center, Lys72, which catalyzes a beta-elimination reaction by forming
      a Schiff base with the C1' of the dRP group.

PMID- 9657673
TI  - Cocrystal structure of protein farnesyltransferase complexed with a farnesyl
      diphosphate substrate.
AB  - Protein farnesyltransferase (FTase) catalyzes the transfer of the hydrophobic
      farnesyl group from farnesyl diphosphate (FPP) to cellular proteins such as Ras
      at a cysteine residue near their carboxy-terminus. This process is necessary for
      the subcellular localization of these proteins to the plasma membrane and is
      required for the transforming activity of oncogenic variants of Ras, making FTase
      a prime target for anticancer therapeutics. The high-resolution crystal structure
      of rat FTase was recently determined, and we present here the X-ray crystal
      structure of the first complex of FTase with a FPP substrate bound at the active
      site. The isoprenoid moiety of FPP binds in an extended conformation in a
      hydrophobic cavity of the beta subunit of the FTase enzyme, and the diphosphate
      moiety binds to a positively charged cleft at the top of this cavity near the
      subunit interface. The observed location of the FPP molecule is consistent with
      mutagenesis data. This binary complex of FTase with FPP leads us to suggest a
      "molecular ruler" hypothesis for isoprenoid substrate specificity, where the
      depth of the hydrophobic binding cavity acts as a ruler discriminating between
      isoprenoids of differing lengths. Although other length isoprenoids may bind in
      the cavity, only the 15-carbon farnesyl moiety binds with its C1 atom in register
      with a catalytic zinc ion as required for efficient transfer to the Ras
      substrate.

PMID- 9657674
TI  - Solution structure of the B-Myb DNA-binding domain: a possible role for
      conformational instability of the protein in DNA binding and control of gene
      expression.
AB  - Double- and triple-resonance heteronuclear NMR spectroscopy have been used to
      determine the high-resolution solution structure of the minimal B-Myb DNA-binding
      domain (B-MybR2R3) and to characterize the specific complex formed with a
      synthetic DNA fragment corresponding to the Myb target site on the Myb-regulated
      gene tom-1. B-MybR2R3 is shown to consist of two independent protein domains (R2
      and R3) joined by a short linker, which have strikingly different tertiary
      structures despite significant sequence similarities. In addition, the C-terminal
      region of B-Myb R2 is confirmed to have a poorly defined structure, reflecting
      the existence of multiple conformations in slow to intermediate exchange. This
      contrasts with the tertiary structure reported for c-MybR2R3, in which both R2
      and R3 have the same fold and the C-terminal region of R2 forms a stable, well
      defined helix [Ogata, K., et al. (1995) Nat. Struct. Biol. 2, 309-320]. The NMR
      data suggest there are extensive contacts between B-MybR2R3 and its DNA target
      site in the complex and are consistent with a significant conformational change
      in the protein on binding to DNA, with one possibility being the formation of a
      stable helix in the C-terminal region of R2. In addition, conformational
      heterogeneity identified in R2 of B-MybR2R3 bound to the tom-1-A target site may
      play an important role in the control of gene expression by Myb proteins.

PMID- 9657675
TI  - Loss of polymerase activity due to Tyr to Phe substitution in the YMDD motif of
      human immunodeficiency virus type-1 reverse transcriptase is compensated by Met
      to Val substitution within the same motif.
AB  - Tyr183 is a constituent of the highly conserved YXDD motif common to all
      retroviral reverse transcriptases. The two aspartates in this motif are the
      crucial members of the catalytic carboxylate triad while residue X, which in the
      case of HIV-1 RT is Met184, is implicated in dNTP substrate recognition and
      fidelity of DNA synthesis. In an attempt to understand the function of Tyr183 in
      the catalytic mechanism, we generated mutants of this residue (Y183F and Y183A)
      and subjected them to in-depth analysis. The efficiency of reverse transcription
      of natural U5-PBS HIV-1 RNA template was severely impaired by both the
      conservative and nonconservative substitutions. The major defect identified was
      at the level of dNTP binding as determined by a 20-80-fold increase in the Km for
      the dNTP substrate on both homopolymeric and heteropolymeric RNA and DNA
      templates. A significant reduction in processivity of DNA synthesis by these
      mutants was also noted. However, the fidelity of DNA synthesis by the Y183F and
      Y183A mutants was increased significantly compared to the wild-type enzyme.
      Interestingly, the reduction in the polymerase activity due to single
      substitution of Tyr to Phe in the YMDD motif is compensated by a second
      substitution of Met to Val in the same motif, herein referred to as the FVDD. The
      loss of dNTP binding as well as decreased processivity of DNA synthesis exhibited
      by the Y183F mutant was also compensated by mutation at the second site.
      Curiously, the double mutant did not exhibit any synergistic effect in regard to
      fidelity of DNA synthesis as might be expected since both the single mutations
      (Y183F, M184V) exhibited enhanced fidelity compared to the wild-type enzyme.
      These data implicate Tyr183 and Met184 as important constituents of the dNTP
      binding pocket. We propose a model which suggests that subtle structural changes
      due to mutation in the flexible beta9-beta10 loop region at the active site of
      the molecule influence the enzyme activity and substrate recognition.

PMID- 9657676
TI  - Solution structure of thermostable cytochrome c-552 from Hydrogenobacter
      thermophilus determined by 1H-NMR spectroscopy.
AB  - The solution structure of a thermostable cytochrome c-552 from a thermophilic
      hydrogen oxidizing bacterium Hydrogenobacter thermophilus was determined by
      proton nuclear magnetic resonance spectroscopy. Twenty structures were calculated
      by the X-PLOR program on the basis of 902 interproton distances, 21 hydrogen
      bonds, and 13 torsion angle constraints. The pairwise average root-mean-square
      deviation for the main chain heavy atoms was 0.91 +/- 0.11 A. The main chain
      folding of the cytochrome c-552 was almost the same as that of Pseudomonas
      aeruginosa cytochrome c-551 that has 59% sequence identity to the cytochrome c
      552 but is less thermostable. We found several differences in local structures
      between the cytochromes c-552 and c-551. In the cytochrome c-552, aromatic-amino
      interactions were uniquely formed between Arg 35 and Tyr 32 and/or Tyr 41, the
      latter also having hydrophobic contacts with the side chains of Tyr 32, Ala 38,
      and Leu 42. Small hydrophobic cores were more tightly packed in the cytochrome c
      552 because of the occupancies of Ala 5, Met 11, and Ile 76, each substituted by
      Phe 7, Val 13, and Val 78, respectively, in the cytochrome c-551. Some of these
      structural differences may contribute to the higher thermostability of the
      cytochrome c-552.

PMID- 9657677
TI  - TIMP-1 contact sites and perturbations of stromelysin 1 mapped by NMR and a
      paramagnetic surface probe.
AB  - Surfaces of the 173 residue catalytic domain of human matrix metalloproteinase 3
      (MMP-3(DeltaC)) affected by binding of the N-terminal, 126 residue inhibitory
      domain of human TIMP-1 (N-TIMP-1) have been investigated using an amide-directed,
      NMR-based approach. The interface was mapped by a novel method that compares
      amide proton line broadening by paramagnetic Gd-EDTA in the presence and absence
      of the binding partner. The results are consistent with the X-ray model of the
      complex of MMP-3(DeltaC) with TIMP-1 (Gomis-Ruth et al. (1997) Nature 389, 77
      81). Residues Tyr155, Asn162, Val163, Leu164, His166, Ala167, Ala169, and Phe210
      of MMP-3(DeltaC) are protected from broadening by the Gd-EDTA probe by binding to
      N-TIMP-1. N-TIMP-1-induced exposure of backbone amides of Asp238, Asn240, Gly241,
      and Ser244 of helix C of MMP-3(DeltaC) to Gd-EDTA confirms that the displacement
      of the N-terminus of MMP-3(DeltaC) occurs not only in the crystal but also in
      solution. These results validate comparative paramagnetic surface probing as a
      means of mapping protein-protein interfaces. Novel N-TIMP-1-dependent changes in
      hydrogen bonding near the active site of MMP-3(DeltaC) are reported. N-TIMP-1
      binding causes the amide of Tyr223 of MMP-3(DeltaC) bound by N-TIMP-1 to exchange
      with water rapidly, implying a lack of the hydrogen bond observed in the crystal
      structure. The backbone amide proton of Asn162 becomes protected from rapid
      exchange upon forming a complex with N-TIMP-1 and could form a hydrogen bond to N
      TIMP-1. N-TIMP-1 binding dramatically increases the rate of amide hydrogen
      exchange of Asp177 of the fifth beta strand of MMP-3(DeltaC), disrupting its
      otherwise stable hydrogen bond.

PMID- 9657678
TI  - Identification of a residue involved in transition-state stabilization in the
      ATPase reaction of DNA gyrase.
AB  - Examination of the X-ray crystal structure of the 43 kDa N-terminal domain of the
      DNA gyrase B protein (GyrB) shows that the majority of the interactions with
      bound ATP are made with subdomain 1 (residues 2-220). However, two residues from
      subdomain 2, Gln335 and Lys337, interact with the gamma-phosphate of ATP. The
      proposed roles for these residues include nucleotide binding, transition-state
      stabilization, and triggering protein conformational changes. We have used site
      directed mutagenesis to convert Gln335 to Asn and Ala and Lys337 to Gln and Ala
      in the N-terminal domain of GyrB. Two of the resultant mutant proteins,
      GyrB43(Q335A) and GyrB43(K337Q), were shown to be correctly folded, and their
      interactions with ATP have been analyzed in detail. The Q335A protein is
      apparently unchanged with regard to nucleotide binding and hydrolysis, whereas
      the K337Q protein shows a modest decrease in nucleotide binding and a drastic
      reduction in ATPase activity. This is manifested by a approximately 10(3)-fold
      decrease in kcat. When the two mutations were moved into full-length GyrB, the
      Q335A mutation again showed little or no effect on activity, whereas the K337Q
      mutation had undetectable supercoiling and ATPase activities. We conclude that
      Gln335 is dispensable for ATP binding and hydrolysis by the gyrase B protein,
      whereas Lys337 has a critical role in the ATPase reaction and is likely to be a
      key residue in transition-state stabilization.

PMID- 9657679
TI  - Role of methionine 56 in the control of the oxidation-reduction potentials of the
      Clostridium beijerinckii flavodoxin: effects of substitutions by aliphatic amino
      acids and evidence for a role of sulfur-flavin interactions.
AB  - Flavodoxins are small electron transferases that participate in low-potential
      electron transfer pathways. The flavodoxin protein is able to separate the two
      redox couples of the noncovalently bound flavin mononucleotide (FMN) cofactor
      through the differential thermodynamic stabilization or destabilization of each
      of its redox states. In the flavodoxin from Clostridium beijerinckii, the sulfur
      atom of methionine 56 is in direct contact with the re or inner face of the
      isoalloxazine ring of the FMN cofactor. In this study, evidence was sought for a
      possible role for sulfur-aromatic (flavin) interactions in the regulation of one
      electron reduction potentials in flavoproteins. Met56 was systematically replaced
      with all the naturally occurring aliphatic amino acids by site-directed
      mutagenesis. Replacement of Met56 with alanine or glycine increased the midpoint
      potentials at pH 7 for the oxidized-semiquinone couple by up to 20 mV compared to
      that of the wild type, while replacement by the longer chain aliphatic residues
      decreased the midpoint potential by >30 mV. The midpoint potential for the
      semiquinone-hydroquinone couple was less negative than that for the wild type for
      all the mutants, increasing by as much as 90 mV for the M56I mutant. For the M56A
      mutant, the loss of approximately 0.5 kcal/mol in the binding energy for oxidized
      FMN and an increase of 1. 6 kcal/mol for the flavin hydroquinone, relative to
      that of the wild type, are responsible for the observed changes in the midpoint
      potentials. The stability of the semiquinone complex of this mutant was not
      affected. The one-election reduction potentials for the M56L, M56I, and M56V
      mutants are also influenced by the differential stabilization of the three redox
      states; however, the semiquinone complex was significantly less stable in these
      proteins. These differences are likely the consequence of the introduction of
      additional steric factors and an apparent structural preference for a smaller or
      more flexible side chain at this position in the semiquinone complex. While the
      other factors may contribute, it is argued that the results obtained for the
      entire group of mutants are consistent with the elimination of important sulfur
      flavin interactions that contribute in part to the stabilization of the oxidized
      and destabilization of the hydroquinone states of the cofactor in this
      flavodoxin. The results of this study also demonstrate unequivocally the
      functional importance of this methionine residue and that it is unique among the
      aliphatic amino acids in its capacity to generate the physiologically relevant
      low reduction potential exhibited by the C. beijerinckii flavodoxin.

PMID- 9657681
TI  - Temperature-controlled activity of DnaK-DnaJ-GrpE chaperones: protein-folding
      arrest and recovery during and after heat shock depends on the substrate protein
      and the GrpE concentration.
AB  - Heat-shock proteins DnaK, DnaJ, and GrpE (KJE) from Escherichia coli constitute a
      three-component chaperone system that prevents aggregation of denatured proteins
      and assists the refolding of proteins in an ATP-dependent manner. We found that
      the rate of KJE-mediated refolding of heat- and chemically denatured proteins is
      decreased at high temperatures. The efficiency and reversibility of protein
      folding arrest during and after heat shock depended on the stability of the
      complex between KJE and the denatured proteins. Whereas a thermostable protein
      was released and partially refolded during heat shock, a thermolabile protein
      remained bound to the chaperone. The apparent affinity of GrpE and DnaJ for DnaK
      was decreased at high temperatures, thereby decreasing futile consumption of ATP
      during folding arrest. The coupling of ATP hydrolysis and protein folding was
      restored after the stress. This strongly indicates that KJE chaperones are heat
      regulated heat-shock proteins which can specifically arrest the folding of
      aggregation-prone proteins during stress and preferentially resume refolding
      under conditions that allow individual proteins to reach and maintain a stable
      native conformation.

PMID- 9657680
TI  - Kinetic characterization of myosin head fragments with long-lived myosin.ATP
      states.
AB  - We have separately expressed the Dictyosteliumdiscoideum myosin II nonhydrolyzer
      point mutations E459V and E476K [Ruppel, K. M., and Spudich, J. A. (1996) Mol.
      Biol. Cell 7, 1123-1136] in the soluble myosin head fragment M761-1R [Anson et
      al. (1996) EMBO J. 15, 6069-6074] and performed transient kinetic analyses to
      characterize the ATPase cycles of the mutant proteins. While the mutations cause
      some changes in mantATP [2'(3')-O-(N-methylanthraniloyl)-ATP] and mantADP
      binding, the most dramatic effect is on the hydrolysis step of the ATPase cycle,
      which is reduced by 4 (E476K) and 6 (E459V) orders of magnitude. Thus, both
      mutant myosin constructs do in fact catalyze ATP hydrolysis but have very long
      lived myosin.ATP states. The E459V mutation allowed for a direct measurement of
      the ATP off rate constant from myosin, which was found to be 2 x 10(-)5 s-1.
      Actin accelerated ATP release from this E459V construct by at least 100-fold.
      Additionally, we found that the affinity of the E476K construct for actin is
      significantly weaker than for the wild-type construct, while the E459V mutant
      interacts with actin normally. Their functional properties and the fact that they
      can be produced and purified in large amounts make the E476K and E459V constructs
      ideal tools to elucidate key structural features of the myosin ATPase cycle.
      These constructs should allow us to address important questions, including how
      binding of ATP to myosin heads results in a >3 order of magnitude reduction in
      actin affinity.

PMID- 9657682
TI  - Engineering steroid 5 beta-reductase activity into rat liver 3 alpha
      hydroxysteroid dehydrogenase.
AB  - Delta 4-3-Ketosteroid-5 beta-reductase (5 beta-reductase) precedes 3 alpha
      hydroxysteroid dehydrogenase (3 alpha-HSD) in steroid hormone metabolism. Both
      enzymes are members of the aldo-keto reductase (AKR) superfamily and possess
      catalytic tetrads differing by a single amino acid. In 3 alpha-HSD, the tetrad
      consists of Tyr55, Lys84, Asp50, and His117, but a glutamic acid replaces His117
      in 5 beta-reductase. By introducing the H117E point mutation into 3 alpha-HSD, we
      engineered 5 beta-reductase activity into the dehydrogenase. Homogeneous H117E 3
      alpha-HSD reduced the double bond in testosterone to form 5 beta
      dihydrotestosterone with kcat = 0.25 min-1 and Km = 19.0 microM and reduced the
      double bond in progesterone to generate 5 beta-dihydroprogesterone with kcat =
      0.97 min-1 and Km = 33.0 microM. These kinetic parameters were similar to those
      reported for homogeneous rat liver 5 beta-reductase [Okuda, A., and Okuda, R.
      (1984) J. Biol. Chem. 259, 7519-7524]. The H117E mutant also reduced 5beta
      dihydrosteroids to 5 beta, 3 alpha-tetrahydrosteroids with a 600-1000-fold
      decrease in kcat/Km versus wild-type 3 alpha-HSD. The ratio of 5 beta-reductase:3
      alpha-HSD activity in the H117E mutant was approximately 1:1. Although the H117A
      mutant reduced Delta 4-3-ketosteroids, the 3 alpha-HSD activity predominated
      because the 5 beta-dihydrosteroids were rapidly converted to the 5 beta,3 alpha
      tetrahydrosteroids. The pH-rate profiles for carbon-carbon double-bond and ketone
      reduction catalyzed by the H117E mutant were superimposable, suggesting a common
      titratable group (pKb = 6.3) for both reactions. In wild-type 3 alpha-HSD, the
      titratable group responsible for 3-ketosteroid reduction has a pKb = 6.9 and is
      assignable to Tyr55. The pH-rate profiles for 3-ketosteroid reduction by the
      H117A mutant were pH-independent. Our data indicate that Tyr55 functions as a
      general acid for both 3 alpha-HSD and 5 beta-reductase activities. We suggest
      that a protonated Glu117 increases the acidity of Tyr55 to promote acid-catalyzed
      enolization of the Delta 4-3-ketosteroid substrate. Further, the identity of
      amino acid 117 determines whether an AKR can function as a 5 beta-reductase by
      reorienting the substrate relative to the nicotinamide cofactor. This study
      provides functional evidence that utilization of modified catalytic residues on
      an identical protein scaffold is important for evolution of enzymatic activities
      within the same metabolic pathway.

PMID- 9657683
TI  - Structural and enzymatic studies of a new analogue of coenzyme B12 with an alpha
      adenosyl upper axial ligand.
AB  - A new analogue of coenzyme B12 (5'-deoxyadenosylcobalamin, AdoCbl), in which the
      configuration of the N-glycosidic bond in the Ado ligand is inverted [(alpha
      ribo)AdoCbl], has been synthesized and its crystal structure determined by X-ray
      diffraction [MoKalpha, lambda = 0.71073 A, monoclinic P212121, a = 16.132(12) A,
      b = 21. 684(15) A, c = 27.30(3) A, 9611 independent reflections, R1 = 0. 0708].
      As suggested by molecular mechanics modeling before the structure was known, the
      Ado ligand lies over the southern quadrant of the molecule, as is the case for
      AdoCbl. The most striking feature of the structure is disorder in the orientation
      of the adenine (Ade) moiety relative to the ribose of the Ado ligand. This was
      resolved with a two-state model in which in the major (0.57 occupancy) conformer
      the A16(O)-A11-A9(N)-A8 dihedral angle is 1.9 degrees and the Ade is virtually
      perpendicular to the corrin ring; in the minor conformer, the Ade is tilted down,
      and this dihedral is -48.7 degrees. The Co-C and axial Co-N bond lengths and the
      Co-C-C bond angle are quite similar to those in AdoCbl. The corrin ring is
      considerably flatter than that of AdoCbl, with a fold angle of 11.7 degrees. The
      molecule was successfully modeled by molecular mechanics (MM), and rotation of
      the Ado ligand relative to the corrin gave rise to four locally minimum
      structures with the Ado in the southern, eastern, northern, or western quadrant,
      with the southern conformation as the global minimum, as is the case with AdoCbl
      itself. Nuclear Overhauser effects (nOe's) observed by two-dimensional (2D) NMR
      were incorporated as restraints in molecular dynamics (MD) and simulated
      annealing (SA) calculations. A MD simulation at 300 K showed that only the
      southern conformation is populated with the Ado ligand confined to an arc from
      over C15 to over C12, while the Ade ring oscillates from perpendicular to
      parallel to the corrin ring. Twenty-seven structures were collected by MD-SA.
      Most of these annealed into the southern conformation, but examples of the other
      conformations were also found. The new analogue is a partially active coenzyme
      for the ribonucleotide reductase from Lactobacillus leichmanii with maximal
      activity that is 9.7% of that of AdoCbl itself, and a very high Km value (245
      microM compared to 0.54 microM for AdoCbl). In addition, the rate constant for
      enzyme-induced carbon-cobalt bond cleavage of (alpha-ribo)AdoCbl is 160-fold
      smaller than that for AdoCbl, and only 1/3 as much cob(II)alamin is produced at
      the active site.

PMID- 9657684
TI  - Proposed steady-state kinetic mechanism for Corynebacterium ammoniagenes FAD
      synthetase produced by Escherichia coli.
AB  - The bifunctional enzyme, FAD synthetase (FS), from Corynebacterium ammoniagenes
      was overproduced in Escherichia coli and purified, and its steady-state kinetic
      properties were investigated. Although FMN is an intermediate product in the
      conversion of riboflavin to FAD, FMN must be released after formation, and then
      rebind for adenylylation. It was shown that adenylylation of FMN is reversible;
      FAD and pyrophosphate can be converted to FMN and ATP by the enzyme. In contrast,
      under the conditions studied, phosphorylation of riboflavin is irreversible. A
      method is described for analysis of two catalytic cycles, occurring on one
      enzyme, which have a substrate and/or product in common. The binding order for
      the phosphorylation cycle of FS was established as riboflavin(in), ATP(in),
      ADP(out), and FMN(out). The order for the adenylylation cycle was ATP(in),
      FMN(in), pyrophosphate(out), and FAD(out). A set of steady-state constants was
      determined, and without additional optimization, these constants were sufficient
      to describe experimental progress curves for conversion of riboflavin to FAD. In
      independent studies, it was demonstrated that FMN binds to apo-FS with a
      dissociation constant of 6-7 microM, which is 2 orders of magnitude higher than
      the KD value for riboflavin. For the steady-state kinetic analysis, this
      represents reversible binding of FMN(out) in the phosphorylation cycle (cycle I),
      which effectively inhibits catalysis in the adenylylation cycle (cycle II).

PMID- 9657686
TI  - High-efficiency incorporation in vivo of tyrosine analogues with altered hydroxyl
      acidity in place of the catalytic tyrosine-14 of Delta 5-3-ketosteroid isomerase
      of Comamonas (Pseudomonas) testosteroni: effects of the modifications on
      isomerase kinetics.
AB  - Versions of the Y55F/Y88F modified form of Delta 5-3-ketosteroid isomerase in
      which the active-site tyrosine-14 is replaced by 2-fluorotyrosine, 3
      fluorotyrosine, and 2,3-difluorotyrosine, amino acids having progressively
      greater acidity of their phenolic hydroxyls, have been expressed in an
      Escherichia coli host and purified to high homogeneity. The steady-state kinetic
      properties of Y55F/Y88F KSI and its fluorotyrosine modified forms have been
      determined. The mechanistic implications of the results are presented and
      discussed.

PMID- 9657685
TI  - Effects of changes in three catalytic residues on the relative stabilities of
      some of the intermediates and transition states in the citrate synthase reaction.
AB  - This work reports the relative importance of the interactions provided by three
      catalytic residues to individual steps in the mechanism of citrate synthase. When
      the side chains of any of the residues (H320, D375, and H274) are mutated, the
      data indicate that they are involved in the stabilization of one or more of the
      transition/intermediate states in the multistep citrate synthase reaction. H320
      forms a hydrogen bond with the carbonyl of oxaloacetate and the alcohols of the
      citryl-coenzyme A and citrate products. Enzymes substituted at H320 (Q, G, N, and
      R) have reaction profiles for which the condensation reaction is cleanly rate
      determining. None of these mutants can activate the carbonyl of oxaloacetate by
      polarization. All these mutants catalyze the necessary proton transfer from the
      methyl group of acetyl-coenzyme A only poorly, a process which occurs in a
      structurally separate site. Furthermore, all H320 mutants hydrolyze the citryl
      coenzyme A intermediate significantly more slowly than does the wild-type. D375
      is the base removing the proton of acetyl-coenzyme A. D375E and D375G have
      greatly diminished ability to catalyze proton transfer from acetyl-CoA. The D375
      mutants polarize the oxaloacetate carbonyl as well as wild-type. For D375E, the
      hydrolysis of citryl-CoA is rate determining. D375G, having no side chain capable
      of acid-base chemistry in either the condensation or hydrolysis reactions is
      nearly completely devoid of activity in any of the reactions catalyzed by the
      wild-type. H274 hydrogen bonds to the carbonyl of acetyl-coenzyme A but also
      forms the back wall of the oxaloacetate-binding site. H274G cannot properly
      activate either oxaloacetate or acetyl-coenzyme A, and the condensation reaction
      is overwhelmingly rate determining. Nonetheless, hydrolysis of the intermediate
      is impaired. All the enzymes except H320R and H274G show kinetic cooperativity
      with CitCoA as substrate, indicating changes in the subunit interactions with
      these latter two mutants. The energetics of citrate synthase are surprisingly
      tightly coupled. All changes affect more than one step in the catalytic cycle.
      Within the condensation reaction, the intermediate of proton transfer must occupy
      a shallow well between transition states close in free energy so that
      perturbations of one have substantial effects on that of the other.

PMID- 9657687
TI  - Reaction paths of iron oxidation and hydrolysis in horse spleen and recombinant
      human ferritins.
AB  - UV-visible spectroscopy, electrode oximetry, and pH stat were used to study
      Fe(II) oxidation and hydrolysis in horse spleen ferritin (HoSF) and recombinant
      human H-chain and L-chain ferritins (HuHF and HuLF). Appropriate test reactions
      and electrode responses were measured, establishing the reliability of oxygen
      electrode/pH stat for kinetics studies of iron uptake by ferritin. Stoichiometric
      ratios, Fe(II)/O2 and H+/Fe(II), and rates of oxygen uptake and proton production
      were simultaneously measured as a function of iron loading of the protein. The
      data show a clear distinction between the diiron ferroxidase site and mineral
      surface catalyzed oxidation of Fe(II). The oxidation/hydrolysis reaction
      attributed to the ferroxidase site has been determined for the first time and is
      given by 2Fe2+ + O2 + 3H2O --> [Fe2O(OH)2]2+ + H2O2 + 2H+ where [Fe2O(OH)2]2+
      represents the hydrolyzed dinuclear iron(III) center postulated to be a mu-oxo
      bridged species from UV spectrometric titration data and absorption band maxima.
      The transfer of iron from the ferroxidase site to the mineral core has been now
      established to be [Fe2O(OH)2]2+ + H2O --> 2FeOOH(core) + 2H+. Regeneration of
      protein ferroxidase activity with time is observed for both HoSF and HuHF,
      consistent with their having enzymatic properties, and is facilitated by higher
      pH (7.0) and temperature (37 degreesC) and by the presence of L-subunit and is
      complete within 10 min. In accord with previous studies, the mineral surface
      reaction is given by 4Fe2+ + O2 + 6H2O --> 4FeOOH(core) + 8H+. As the protein
      progressively acquires iron, oxidation/hydrolysis increasingly shifts from a
      ferroxidase site to a mineral surface based mechanism, decreasing the production
      of H2O2.

PMID- 9657688
TI  - Q-band resonance Raman spectra of oxidized and reduced mitochondrial bc1
      complexes.
AB  - Recently published crystallographic studies of mitochondrial bc1 complexes have
      stimulated renewed interest in the active site architecture of these important
      integral membrane proteins. We present resonance Raman spectra obtained via
      variable excitation within the heme Q-band from samples poised in several
      different net redox states. Appropriate subtraction and polarization analysis
      allows the vibrational behavior of the individual heme bL,bH, and c1 sites to be
      assessed. The spectra of the b hemes are particularly noteworthy. They exhibit
      evidence for a protonation equilibrium involving heme axial ligands and reveal a
      marked structural heterogeneity at the heme bH site that most likely involves
      nonplanar distortions of the macrocycle. The possible implications of these
      findings for heme functionality are discussed.

PMID- 9657689
TI  - The PsaE subunit is required for complex formation between photosystem I and
      flavodoxin from the cyanobacterium Synechocystis sp. PCC 6803.
AB  - The photoreduction of the oxidized and the semiquinone form of flavodoxin by
      photosystem I particles (PSI) from the wild type and a psaE deletion strain from
      the cyanobacterium Synechocystis sp. PCC 6803 was analyzed by flash-absorption
      spectroscopy to investigate a possible involvement of the PsaE subunit in this
      photoreduction process. The kinetics of the reduction of oxidized flavodoxin
      display a single-exponential component for both PSI preparations. Limiting
      electron transfer rates kobs of approximately 500 and approximately 900 s -1 are
      deduced for the wild type and PSI from the psaE-less mutant, respectively,
      indicating that the PsaE subunit is not important for this photoreduction
      process. In the case of wild-type PSI, the reduction of flavodoxin semiquinone is
      a biphasic process, displaying a fast first-order phase with a t1/2 of
      approximately 13 micro(s) which is then followed by a slower, concentration
      dependent phase, for which a second-order rate constant k2 of 2.2 x 10(8) M-1 cm
      1 is calculated. In contrast, photoreduction of the semiquinone by PSI from the
      psaE-less mutant is monoexponential, displaying only one second-order component
      with a second-order rate constant similar to those observed for wild-type PSI (k2
      = 1.5 x 10(8) M-1 cm-1). The fast first-order component which is interpreted as
      an electron transfer process within a preformed complex between flavodoxin
      semiquinone and PSI is almost completely absent in the reduction of flavodoxin by
      the PsaE-less PSI. A similar loss of the fast phase is also observed for the
      photoreduction of flavodoxin semiquinone by PSI from a Synechococcus elongatus
      psaE-less mutant. Upon reconstitution of isolated PsaE to the PsaE-less PSI in
      vitro, approximately 80% of the fast first-order kinetic component is recovered,
      indicating that PsaE is required for high-affinity binding of the flavodoxin
      semiquinone to PSI. In addition, chemical cross-linking assays show that
      flavodoxin can no longer be cross-linked to PSI in detectable amounts when PsaE
      is missing on the reaction center. Taken together, these experiments indicate
      that the PsaE subunit is required for complex formation between PSI and
      flavodoxin but is not required for an efficient forward electron transfer from
      photosystem I to both forms of flavodoxin.

PMID- 9657690
TI  - Incorrect folding of steroidogenic acute regulatory protein (StAR) in congenital
      lipoid adrenal hyperplasia.
AB  - Steroidogenic acute regulatory protein (StAR) rapidly stimulates the movement of
      cholesterol into adrenal and gonadal mitochondria to mediate the acute
      steroidogenic response; StAR mutations cause potentially lethal congenital lipoid
      adrenal hyperplasia (lipoid CAH). Bacterially expressed wild-type StAR and four
      amino acid replacement/deletion mutants that cause lipoid CAH were purified to
      apparent homogeneity. Sedimentation equilibrium ultracentrifugation showed that
      all five proteins were monomeric and fit a globular protein model of the correct
      molecular mass. Circular dichroism (CD) spectra of both the wild-type and mutants
      showed minima near 208 and 222 nm, confirming the presence of substantial alpha
      helical structure. However, subtle differences in the CD signals of the wild-type
      and mutants in the far-UV and stronger differences in near-UV indicated
      differences in protein folding. The amide I and II bands in the 1400-1700 cm-1
      region of Fourier transform infrared spectra showed that the proteins fell into
      two groups. The wild-type and a partially active conservative mutant were
      predominantly alpha-helical with some intramolecular beta-sheet. By contrast,
      three mutants that lost charged residues retained much of their alpha-helical
      structure, but also tended to form intermolecular beta-sheets. Urea at 2.0 or 4.0
      M had less effect on the CD spectrum of the wild-type than of the mutants,
      particularly those having lost a charged residue; 50 mM guanidinium hydrochloride
      did not alter the CD spectrum of the wild-type, but elicited dramatic changes to
      the secondary structure in all four mutants. Despite this, thermal melting curves
      of the mutant proteins in 50 mM guanidinium hydrochloride showed surprising
      stability, even exceeding that of the wild-type protein. These data suggest that
      the StAR amino acid replacement mutants that cause lipoid CAH are inactive
      because of fairly gross errors in protein folding, probably due to the loss of
      salt bridges that stabilize the tertiary structure.

PMID- 9657691
TI  - Phosphatidylinositol 3,4,5-trisphosphate triggers platelet aggregation by
      activating Ca2+ influx.
AB  - Exogenous phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] stimulates
      the aggregation of washed rabbit platelets in a Ca2+- and dose-dependent manner.
      This aggregation is reversible at low PtdIns(3,4,5)P3 levels, but becomes
      irreversible when the concentration exceeds a threshold of about 20 microM. Other
      D-3 and D-4 phosphoinositides examined, including phosphatidylinositol 3, 4
      bisphosphate [PtdIns(3,4)P2], phosphatidylinositol 4, 5-bisphosphate
      [PtdIns(4,5)P2], and phosphatidylinositol 3-monophosphate [PtdIns(3)P], fail to
      exert appreciable platelet activation at comparable concentrations. In addition,
      PtdIns(3,4, 5)P3 can reverse the inhibitory effect of wortmannin on thrombin
      induced platelet aggregation. Taken together with the observation that
      PtdIns(3,4,5)P3 is readily incorporated into cell membranes, these findings
      reaffirm the second messenger role of PtdIns(3,4,5)P3 in thrombin receptor
      activation. The existence of a PtdIns(3,4,5)P3-dependent Ca2+ entry system on
      platelet membranes is supported by the partial inhibition of thrombin-induced
      Ca2+ influx by wortmannin. Evidence suggests that this system differs from
      receptor-operated nonselective Ca2+ channels. However, the mechanism by which
      PtdIns(3,4,5)P3 facilitates Ca2+ entry remains unclear. Although PtdIns(3,4,5)P3
      has been known to stimulate phospholipase C-gamma (PLC-gamma), internal Ca2+
      mobilization does not play a significant role in the cytosolic Ca2+ increase in
      response to PtdIns(3,4,5)P3 stimulation. Collectively, these data provide a
      putative link between PtdIns(3,4,5)P3 and Ca2+ signaling, which may, in part,
      account for the regulatory function of PtdIns(3,4,5)P3 during platelet
      aggregation. Moreover, this study bears out the notion that individual PI 3
      kinase lipid products play distinct roles in the regulation of cellular
      functions.

PMID- 9657692
TI  - Core domain mutation (S86Y) selectively inactivates polyubiquitin chain synthesis
      catalyzed by E2-25K.
AB  - The mammalian ubiquitin conjugating enzyme known as E2-25K catalyzes the
      synthesis of polyubiquitin chains linked exclusively through K48-G76 isopeptide
      bonds. The properties of truncated and chimeric forms of E2-25K suggest that the
      polyubiquitin chain synthesis activity of this E2 depends on specific
      interactions between its conserved 150-residue core domain and its unique 50
      residue tail domain [Haldeman, M. T., Xia, G., Kasperek, E. M., and Pickart, C.
      M. (1997) Biochemistry 36, 10526-10537]. In the present study, we provide strong
      support for this model by showing that a point mutation in the core domain (S86Y)
      mimics the effect of deleting the entire tail domain: the ability to form an E2
      approximately ubiquitin thiol ester is intact, while conjugation activity is
      severely inhibited (>/=100-fold reduction in kcat/Km). The properties of E2-25K
      enzymes carrying the S86Y mutation indicate that this mutation strengthens the
      interaction between the core and tail domains: both free and ubiquitin-bound
      forms of S86Y-25K are completely resistant to tryptic cleavage at K164 in the
      tail domain, whereas wild-type enzyme is rapidly cleaved at this site. Other
      properties of S86Y-26K suggest that the active site of this mutant enzyme is more
      occluded than the active site of the wild-type enzyme. (1) Free S86Y-25K is
      alkylated by iodoacetamide 2-fold more slowly than the wild-type enzyme. (2) In
      assays of E2 approximately ubiquitin thiol ester formation, S86Y-25K shows a 4
      fold reduced affinity for E1. (3) The ubiquitin thiol ester adduct of S86Y-25K
      undergoes (uncatalyzed) reaction with dithiothreitol 3-fold more slowly than the
      wild-type thiol ester adduct. One model to accommodate these findings postulates
      that an enhanced interaction between the core and tail domains, induced by the
      S86Y mutation, causes a steric blockade at the active site which prevents access
      of the incoming ubiquitin acceptor to the thiol ester bond. Consistent with this
      model, the S86Y mutation inhibits ubiquitin transfer to macromolecular acceptors
      (ubiquitin and polylysine) more strongly than transfer to small-molecule
      acceptors (free lysine and short peptides). These results suggest that unique
      residues proximal to E2 active sites may influence specific function by mediating
      intramolecular interactions.

PMID- 9657693
TI  - Human cytomegalovirus protease complexes its substrate recognition sequences in
      an extended peptide conformation.
AB  - Substrate hydrolysis by human cytomegalovirus (HCMV) protease is essential to
      viral capsid assembly. The interaction of HCMV protease and the N-terminal
      cleavage products of the hydrolysis of R- and M-site oligopeptide substrate
      mimics (R and M, respectively, which span the P9-P1 positions) was studied by NMR
      methods. Protease-induced differential line broadening indicated that ligand
      binding is mediated by the P4-P1 amino acid residues of the peptides. A well
      defined extended conformation of R from P1 through P4 when complexed to HCMV
      protease was evidenced by numerous transferred nuclear Overhauser effect (NOE)
      correlations for the peptide upon addition of the enzyme. NOE cross-peaks between
      the P4 and P5 side chains placing these two groups in proximity indicated a
      deviation from the extended conformation starting at P5. Similar studies carried
      out for the M peptide also indicated an extended peptide structure very similar
      to that of R, although the conformation of the P5 glycine could not be
      established. No obvious variation in structure between bound R and M (notably at
      P4, where the tyrosine of the R-site has been suggested to play a key role in
      ligand binding) could be discerned that might explain the observed differences in
      processing rates between R- and M-sequences. Kinetic studies, utilizing R- and M
      site peptide substrates for which the P5 and P4 residues were separately
      exchanged, revealed that these positions had essentially no influence on the
      specificity constants (kcat/KM). In sharp contrast, substitution of the P2
      residue of an M-site peptide changed its specificity constant to that of an R
      site peptide substrate, and vice versa.

PMID- 9657694
TI  - Quantitative hydroxyl radical footprinting reveals cooperative interactions
      between DNA-binding subdomains of PU.1 and IRF4.
AB  - Quantitative hydroxyl radical footprinting and fluorescence polarization
      measurements have been used to determine the dissociation constants (Kd) of
      complexes between the ets domain of the murine transcription factor PU.1 and
      three different DNA fragments. Two natural PU.1 binding sites, the SV40 enhancer
      site and the lambdaB motif of Iglambda2-4 enhancer, were used as well as the PU.1
      binding site present in the crystallized PU.1-DNA complex. With the use of
      quantitative hydroxyl radical footprinting we obtained binding isotherms for
      individual protected nucleotides and contact sites on both strands of the DNA. Kd
      values of (1.53 +/- 0. 12) x 10(-)8 M were found for the lambdaB element, (3.60
      +/- 0.65) x 10(-)8 M for the SV40 enhancer site, and (2.28 +/- 0.27) x 10(-)8 M
      for the sequence used in the crystal structure. In addition, the binding of a
      second protein, the DNA binding domain of IRF4, to the lambdaB site by itself and
      in the presence of PU.1 was analyzed. The IRF4 DBD shows three footprints on the
      TTCC strand and one footprint on the GGAA strand of the lambdaB element. The
      dissociation constant for the binary IRF4 DBD-lambdaB complex equals (5.59 +/-
      0.60) x 10(-)7 M. The Kd value of the IRF4-lambdaB interaction is reduced by a
      factor of 5 in the presence of two different DNA-bound PU.1 protein constructs,
      PU.1 DBD and a PU.1 construct containing the PEST domain (PU.1-PEST). A similar
      decrease of the Kd value was observed for the binding of PU.1-PEST in the
      presence of DNA-bound IRF4 DBD demonstrating a cooperative interaction between
      the PU. 1-PEST and IRF4 DBD. On the basis of the hydroxyl radical footprints in
      the ternary PU.1/IRF4/lambdaB complex, a model for the interactions between the
      two proteins and the lambdaB site was developed. The DNA binding domains of both
      proteins bind the DNA in the major groove with potential protein-protein
      interactions near the intervening minor groove.

PMID- 9657695
TI  - Solution structure of the oxidized Fe7S8 ferredoxin from the thermophilic
      bacterium Bacillus schlegelii by 1H NMR spectroscopy.
AB  - The solution structure of the paramagnetic seven-iron ferredoxin from Bacillus
      schlegelii in its oxidized form has been determined by 1H NMR. The protein, which
      contains 77 amino acids, is thermostable. Seventy-two residues and 79% of all
      theoretically expected proton resonances have been assigned. The structure has
      been determined through torsion angle dynamics calculations with the program
      DYANA, using 966 meaningful NOEs (from a total of 1305), hydrogen bond
      constraints, and NMR derived dihedral angle constraints for the cluster ligating
      cysteines, and by using crystallographic information to build up the two
      clusters. Afterwards, restrained energy minimization and restrained molecular
      dynamics were applied to each conformer of the family. The final family of 20
      structures has RMSD values from the mean structure of 0.68 A for the backbone
      atoms and of 1.16 A for all heavy atoms. The contributions to the thermal
      stability of the B. schlegelii ferredoxin are discussed by comparing the present
      structure to that of the less stable Azotobacter vinelandii ferredoxin I which is
      the only other available structure of a bacterial seven-iron ferredoxin. It is
      proposed that the hydrophobic interactions and the hydrogen bond network linking
      the N-terminus and the C-terminus together and a high number of salt bridges
      contribute to the stability.

PMID- 9657696
TI  - Implication of DNA-dependent protein kinase in an early, essential, local
      phosphorylation event during end-joining of DNA double-strand breaks in vitro.
AB  - Previous work with Xenopus egg extracts suggested that a wortmannin-sensitive
      protein phosphorylation event precedes both the removal of modified termini from
      DNA double-strand break ends and the joining of unmodified ends. To assess the
      possible role of DNA-dependent protein kinase in effecting this phosphorylation,
      both DNA end-joining and DNA-stimulated phosphorylation were examined in the
      presence of various inhibitors. Linear but not supercoiled DNA stimulated the
      phosphorylation of several endogenous proteins in the extracts, including species
      of approximately 48, 87, and 96 kDa. This phosphorylation was selectively
      suppressed by the kinase inhibitors wortmannin, dimethylaminopurine, and
      LY294002, with a dose response that in each case paralleled the inhibition of DNA
      end-joining. If wortmannin was added while the end-joining reaction was in
      progress, end-joining of DNA already present in the reaction continued for some
      time, but newly added DNA was not joined or processed at all. Ends with 3'
      hydroxyl termini were joined much faster than those with 3'-phosphoglycolate
      termini, although both were equally effective in stimulating protein
      phosphorylation. The results support a role for DNA-dependent protein kinase in
      regulating end-joining in vitro, and suggest that at least one of the necessary
      phosphorylations involves a protein bound at or near the DNA end to be joined. In
      contrast, nuclear extracts from human cells joined double-strand breaks with
      normal but not modified termini, and the joining was unaffected by kinase
      inhibitors, suggesting that the dominant mechanism of end-joining in these
      extracts did not involve DNA-PK.

PMID- 9657697
TI  - The terminal adenosine of tRNA(Gln) mediates tRNA-dependent amino acid
      recognition by glutaminyl-tRNA synthetase.
AB  - Sequence-specific interactions between Escherichia coli glutaminyl-tRNA
      synthetase and tRNA(Gln) have been shown to determine the apparent affinity of
      the enzyme for its cognate amino acid glutamine during aminoacylation.
      Specifically, structural and biochemical studies suggested that residues Asp66,
      Tyr211, and Phe233 in glutaminyl-tRNA synthetase could potentially facilitate
      cognate amino recognition through their specific interactions with both A76 of
      tRNA(Gln)++ and glutamine. These residues were randomly mutated and the resulting
      glutaminyl-tRNA synthetase variants were screened in vivo for changes in their
      ability to recognize noncognate tRNAs and retention of tRNA-glutaminylation
      activity. When the variants selected in this way were characterized in vitro,
      they all showed dramatic decreases in apparent affinity (KM) for glutamine but
      little or no change in cognate tRNA affinity. Conservative replacements such as
      Y211F, F233L, and D66E resulted in 60-, 19-, and 18-fold increases compared to
      wild-type in the KM for glutamine, respectively, but had little effect on the
      turnover number (kcat). Nonconservative replacements affected both KM for
      glutamine and kcat; Y211S, F233D, and D66F displayed 1700, 3700, and 1200-fold
      decreases in kcat/KM for glutamine compared to wild-type. Double mutant cycle
      analysis indicated that Tyr211, and Phe233 interact strongly to enhance glutamine
      binding. These data now show that Asp66, Tyr211 and Phe233 mediate tRNA-dependent
      cognate amino acid recognition via the invariant 3'-terminal adenosine of
      tRNA(Gln).

PMID- 9657698
TI  - Specific isoprenyl group linked to transducin gamma-subunit is a determinant of
      its unique signaling properties among G-proteins.
AB  - Among 11 subtypes of heterotrimeric G-protein gamma-subunit, gamma1 (rod), gamma8
      (cone) and gamma11 are modified with farnesyl while the others are modified with
      geranylgeranyl at the C-terminus. To understand the role of specific
      isoprenylation (farnesylation) of retinal transducin, we examined how and to what
      extent the type of isoprenyl group affects transducin-beta gamma (beta1 gamma1)
      functions such as interactions with membranes, Galpha/receptor, and effectors. To
      this end, the C-terminal farnesylation signal sequence (CVIS) of gamma1 was
      replaced by a geranylgeranylation signal (CVIL), and the resultant mutant (S74L)
      or wild-type (WT) gamma1 was coexpressed with beta1 in the baculovirus-Tn5 insect
      cell system. Both gamma1WT and gamma1S74L expressed as a beta gamma complex were
      mixtures modified with farnesyl and geranylgeranyl groups. The ratio of farnesyl
      to geranylgeranyl in preparations of beta1 gamma1WT and beta1 gamma1S74L purified
      from the Tn5 cell membrane fraction was about 1:2 and 1:6, respectively. These
      two forms of recombinant beta1 gamma1 and retinal beta1 gamma1 were different in
      their abilities to associate with rod outer segment membranes with the following
      rank order: beta1 gamma1S74L > beta1 gamma1WT > retinal beta1 gamma1.
      Functionally, beta1 gamma1S74L was the most potent to promote pertussis toxin
      catalyzed ADP ribosylation of transducin-alpha (Talpha), to stimulate
      metarhodopsin II-catalyzed GTPgammaS-binding reaction to Talpha and to modulate
      adenylyl cyclase and phospholipase C activities. All of the beta1 gamma1
      functions absolutely required the isoprenylation of the gamma-subunit. As for the
      interaction with Goalpha and adenylyl cyclase, predominantly geranylgeranylated
      beta1 gamma1S74L was less effective than geranylgeranylated beta1 gamma2 purified
      from bovine brain. These results demonstrate that the properties of Gbeta gamma
      are strongly affected by the type of functionally indispensable isoprenylation in
      addition to the amino acid sequence of Ggamma. The relative contribution of the
      two factors depends on proteins with which Gbeta gamma interacts.

PMID- 9657699
TI  - Roles of individual disulfide bonds in the stability and folding of an omega
      conotoxin.
AB  - Although it contains only 25 amino acid residues, omega-conotoxin MVIIA folds
      into a well-defined three-dimensional structure that is stabilized by 3 disulfide
      bonds. To assess the contributions of the disulfides to folding and stability,
      three analogues, each with one pair of disulfide-bonded Cys residues replaced
      with Ala, were prepared and characterized. The analogues also contained a C
      terminal Gly residue that is believed to be present when the peptide folds in
      vivo and has been shown previously to stabilize the native structure. Circular
      dichroism spectra and biological assays of the analogues indicated that removing
      any one of the disulfides greatly destabilized the native conformation. The two
      disulfides in each analogue were also reduced much more rapidly than in the
      native form with three disulfides. When the analogues were fully reduced and
      allowed to form disulfides in the presence of oxidized and reduced glutathione,
      the native disulfides were not formed in preference to non-native disulfides,
      further indicating that the forms with two-native disulfides are not
      significantly stabilized by noncovalent interactions. However, the measured
      equilibrium constants for disulfide formation indicate that forming any two of
      the three native disulfides leads to an effective concentration of approximately
      25-50 M for the two remaining thiols. The two-disulfide analogues thus appear to
      represent a stage of folding in which the polypeptide is constrained to a
      distribution of relatively compact conformations that greatly favor formation of
      the third disulfide and the final folded structure.

PMID- 9657701
TI  - Retroviral envelope glycoprotein processing: structural investigation of the
      cleavage site 

PMID- 9657702
TI  - Elsewhere in biology

PMID- 9657700
TI  - Probing the nucleotide binding sites of axonemal dynein with the fluorescent
      nucleotide analogue 2'(3')-O-(-N-Methylanthraniloyl)-adenosine 5'-triphosphate.
AB  - MantATP [2'(3')-O-(-N-methylanthraniloyl)-adenosine 5'-triphosphate] was employed
      as a fluorescence probe of the nucleotide-binding sites of dynein from sea urchin
      sperm flagella. MantATP binds specifically with enhanced fluorescence
      (approximately 2.2-fold), homogeneous lifetime (8.4 ns), and high anisotropy (r
      approximately 0.38) to dynein and can be displaced by ATP and ADP added to the
      medium. The association constants of mantATP complexed with dynein were
      determined from anisotropy titration data. Using a multiple stepwise equilibrium
      model, the average values of the first two association constants are K1 = 2.7 x
      10(5) M-1 and K2 = 1.8 x 10(4) M-1. This value of K1 is 7-8 times higher than
      that found previously for unsubstituted ATP, whereas K2 is little changed [Mocz
      and Gibbons (1996) Biochemistry 35, 9204-9211]. The lower-affinity binding sites,
      K3 and K4, observed previously could not be studied with mantATP within the
      available protein concentrations. The alpha and beta heavy chain subfractions
      have binding parameters similar to those of intact dynein. Formation of the
      stable ternary complex of mantATP with dynein and monomeric vanadate is
      accompanied by only a moderate increase in the binding affinities. Oligomeric
      vanadate reduces the binding affinities by approximately 50%. Addition of TritonX
      100, methanol, or various salts changes the binding affinities by up to 50%,
      suggesting that the microenvironment of the nucleotide-binding sites involves
      significant contributions from both polar and apolar interactions. The distinct
      affinities of the individual binding sites are consistent with a physiological
      role in regulating nucleotide binding.

PMID- 9657703
TI  - Downstream in America.

PMID- 9657704
TI  - MCS: a sensitive issue.

PMID- 9657705
TI  - Trial and error: should pregnant women be research subjects?

PMID- 9657706
TI  - Rock 'n' Roll Refrigerator.

PMID- 9657707
TI  - Comparative activity of human carcinogens and NTP rodent carcinogens in the mouse
      bone marrow micronucleus assay: an integrative approach to genetic toxicity data
      assessment.
AB  - The mouse bone marrow micronucleus (MN) assay holds a key position in all schemes
      for detecting potential human carcinogens and mutagens. It was therefore of
      concern when Shelby et al. reported that only 5 of 25 rodent carcinogens defined
      by the U.S. NTP were positive in the assay. Further, each of these positive
      responses was weak and indistinguishable from the 4 positive responses observed
      among the 24 NTP noncarcinogens tested. To focus these findings, the activity in
      the MN assay of 26 human carcinogens, 6 reference rodent genotoxins, and the 9
      NTP chemicals positive in the MN assay have been displayed in a common format.
      This involved plotting the minimum positive dose level (expressed as
      mumole/kilogram) and the maximum fold-increase in micronucleated polychromatic
      erythrocytes frequency observed at any dose level. By displaying the high
      sensitivity of the micronucleus assay to the reference human and rodent
      genotoxins, this analysis emphasizes the weakness in the MN assay responses given
      by the NTP carcinogens reported by Shelby et al. This, in turn, poses questions
      about the intrinsic hazard of this selection of NTP rodent carcinogens. Using
      fotemustine and vitamin C as models of a toxic and a nontoxic chemical known to
      be active in the MN assay, this analysis describes a method by which their
      relative potential human hazard can be distinguished (a synthetic, as opposed to
      an analytical approach to data assessment). The possibility that some weak
      responses observed in the MN assay at elevated dose levels may be stress induced
      is considered.

PMID- 9657708
TI  - A biomarker approach to assessing xenobiotic exposure in Atlantic tomcod from the
      North American Atlantic coast.
AB  - We determined levels of hepatic cytochrome P4501A (CYP1A) mRNA, hepatic DNA
      adducts, and fluorescent aromatic compounds (FACs) in bile, a measure of exposure
      to polyaromatic hydrocarbons, in Atlantic tomcod from six river systems ranging
      from highly polluted to relatively pristine on the northeast North American coast
      (the Hudson River, New York; the St. Lawrence River, Quebec; the Miramichi River,
      New Brunswick; the Saco and Royal rivers, Maine; and the Margaree River, Nova
      Scotia). Hudson River tomcod showed the greatest response for all parameters, and
      tomcod from the Margaree River exhibited the least response. Tomcod from the
      Miramichi River exhibited marked induction of CYP1A mRNA but low levels of
      hepatic DNA adducts and biliary FACs, whereas fish from the St. Lawrence River
      showed no induction of CYP1A mRNA and moderately elevated levels of DNA adducts
      and biliary FACs. In tomcod from the Hudson and Miramichi rivers, the levels of
      CYP1A mRNA were 28 times and 14 times, respectively, as great as the levels in
      fish from the St. Lawrence, Saco/Royal, and Margaree rivers. Mean levels of DNA
      adducts varied from 120 nmol adducts/mol bases in Hudson River tomcod to < 3 nmol
      adducts/mol bases in fish from the Miramichi and Margaree rivers. Concentrations
      of FACs in the bile of tomcod from the Hudson and St. Lawrence rivers were 8 and
      1.8 times, respectively, as great as the concentrations in tomcod from the
      Miramichi River and Margaree River. In tomcod from the Hudson River, all three
      biomarkers were markedly elevated; in the St. Lawrence River two biomarkers were
      elevated, in the Miramichi River one was elevated, but no biomarker was
      substantially elevated in fish from the Saco/Royal and Margaree rivers. Elevated
      levels of hepatic DNA adducts and biliary FACs in tomcod from the Hudson River
      suggest increased exposure to PAHs, consistent with previous studies.

PMID- 9657709
TI  - High levels of mercury contamination in multiple media of the Carson River
      drainage basin of Nevada: implications for risk assessment.
AB  - Approximately 5.5 x 109 g (4.0 x 105) of mercury was discharged into the Carson
      River Drainage Basin of west-central Nevada during processing of the gold- and
      silver-rich Comstock ore in the late 1800s. For the past 13 decades, mercury has
      been redistributed throughout 500 km2 of the basin, and concentrations are some
      of the highest reported values in North America. This article documents the
      concentrations of mercury in the air, water, and substrate at both contaminated
      and noncontaminated sites within the basin and discusses the implications for
      risk assessment. At contaminated areas, the range of mercury concentrations are
      as follows: mill tailings, 3-1610 micrograms/g; unfiltered reservoir water, 53
      591 ng/l; atmospheric vapor, 2-294 ng/m3. These values are three to five orders
      of magnitude greater than natural background. In all media at contaminated sites,
      concentrations are spatially variable, and air and water mercury concentrations
      vary temporally. The study are in situated in a natural mercuriferous belt, and
      regional background mercury concentrations in all environmental media are higher
      than values typically cited for natural background. As a mercury-contaminated
      site in North America, the Carson River Drainage Basin is unusual for a number of
      reasons, including its location in a natural mercuriferous belt, high and
      sustained levels of anthropogenic mercury inputs, long exposure time, aridity of
      the climate, and the riparian setting in an arid landscape, where biological
      activity is concentrated in the same areas that contain high levels of mercury in
      multiple media.

PMID- 9657710
TI  - PCBs as environmental estrogens: turtle sex determination as a biomarker of
      environmental contamination.
AB  - Polychlorinated biphenyls (PCBs) are widespread, low-level environmental
      pollutants associated with adverse health effects such as immune suppression and
      teratogenicity. There is increasing evidence that some PCB compounds are capable
      of disrupting reproductive and endocrine function in fish, birds, and mammals,
      including humans, particularly during development. Research on the mechanism
      through which these compounds act to alter reproductive function indicates
      estrogenic activity, whereby the compounds may be altering sexual
      differentiation. Here we demonstrate the estrogenic effect of some PCBs by
      reversing gonadal sex in a reptile species that exhibits temperature-dependent
      sex determination.

PMID- 9657711
TI  - Major bacterial contribution to marine dissolved organic nitrogen 
AB  - Next to N2 gas, the largest pool of reduced nitrogen in the ocean resides in the
      enormous reservoir of dissolved organic nitrogen (DON). The chemical identity of
      most of this material, and the mechanisms by which it is cycled, remain
      fundamental questions in contemporary oceanography. Amino acid enantiomeric
      ratios in the high molecular weight fraction of DON from surface and deep water
      in three ocean basins show substantial enrichment in D enantiomers of four amino
      acids. The magnitude and pattern of these D/L enrichments indicate that
      peptidoglycan remnants derived from bacterial cell walls constitute a major
      source of DON throughout the sea. These observations suggest that structural
      properties of specific bacterial biopolymers, and the mechanisms for their
      accumulation, are among the central controls on long-term cycling of dissolved
      organic nitrogen in the sea.

PMID- 9657712
TI  - The CO2 balance of unproductive aquatic ecosystems 
AB  - Community respiration (R) rates are scaled as the two-thirds power of the gross
      primary production (P) rates of aquatic ecosystems, indicating that the role of
      aquatic biota as carbon dioxide sources or sinks depends on its productivity.
      Unproductive aquatic ecosystems support a disproportionately higher respiration
      rate than that of productive aquatic ecosystems, tend to be heterotrophic (R >
      P), and act as carbon dioxide sources. The average P required for aquatic
      ecosystems to become autotrophic (P > R) is over an order of magnitude greater
      for marshes than for the open sea. Although four-fifths of the upper ocean is
      expected to be net heterotrophic, this carbon demand can be balanced by the
      excess production over the remaining one-fifth of the ocean.

PMID- 9657713
TI  - Primary production of the biosphere: integrating terrestrial and oceanic
      components 
AB  - Integrating conceptually similar models of the growth of marine and terrestrial
      primary producers yielded an estimated global net primary production (NPP) of
      104.9 petagrams of carbon per year, with roughly equal contributions from land
      and oceans. Approaches based on satellite indices of absorbed solar radiation
      indicate marked heterogeneity in NPP for both land and oceans, reflecting the
      influence of physical and ecological processes. The spatial and temporal
      distributions of ocean NPP are consistent with primary limitation by light,
      nutrients, and temperature. On land, water limitation imposes additional
      constraints. On land and ocean, progressive changes in NPP can result in altered
      carbon storage, although contrasts in mechanisms of carbon storage and rates of
      organic matter turnover result in a range of relations between carbon storage and
      changes in NPP.

PMID- 9657714
TI  - Abrupt shift in subsurface temperatures in the tropical pacific associated with
      changes in El Nino 
AB  - Radiocarbon (14C) content of surface waters inferred from a coral record from the
      Galapagos Islands increased abruptly during the upwelling season (July through
      September) after the El Nino event of 1976. Sea-surface temperatures (SSTs)
      associated with the upwelling season also shifted after 1976. The synchroneity of
      the shift in both 14C and SST implies that the vertical thermal structure of the
      eastern tropical Pacific changed in 1976. This change may be responsible for the
      increase in frequency and intensity of El Nino events since 1976.

PMID- 9657715
TI  - Solidus of Earth's deep mantle 
AB  - The solidus of a pyrolite-like composition, approximating that of the lower
      mantle, was measured up to 59 gigapascals by using CO2 laser heating in a diamond
      anvil cell. The solidus temperatures are at least 700 kelvin below the melting
      temperatures of magnesiowustite, which in the deep mantle has the lowest melting
      temperatures of the three major components-magnesiowustite, Mg-Si-perovskite, and
      Ca-Si-perovskite. The solidus in the deep mantle is more than 1500 kelvin above
      the average present-day geotherm, but at the core-mantle boundary it is near the
      core temperature. Thus, partial melting of the mantle is possible at the core
      mantle boundary.

PMID- 9657716
TI  - A reduction-pyrolysis-catalysis synthesis of diamond 
AB  - Diamond powder was synthesized through a metallic reduction-pyrolysis-catalysis
      route with the reaction of carbon tetrachloride and sodium at 700 degreesC, in
      which the sodium was used as reductant and flux. This temperature is much lower
      than that of traditional methods. The x-ray powder diffraction patterns showed
      three strong peaks of diamond. The Raman spectrum showed a sharp peak at 1332
      inverse centimeters, which is characteristic of diamond. Although the yield was
      only 2 percent, this method is a simple means of forming diamond.

PMID- 9657717
TI  - MR imaging contrast enhancement based on intermolecular zero quantum coherences.
AB  - A new method for magnetic resonance imaging (MRI) based on the detection of
      relatively strong signal from intermolecular zero-quantum coherences (iZQCs) is
      reported. Such a signal would not be observable in the conventional framework of
      magnetic resonance; it originates in long-range dipolar couplings (10 micrometers
      to 1 millimeter) that are traditionally ignored. Unlike conventional MRI, where
      image contrast is based on variations in spin density and relaxation times (often
      with injected contrast agents), contrast with iZQC images comes from variations
      in the susceptibility over a distance dictated by gradient strength. Phantom and
      in vivo (rat brain) data confirm that iZQC images give contrast enhancement. This
      contrast might be useful in the detection of small tumors, in that susceptibility
      correlates with oxygen concentration and in functional MRI.

PMID- 9657718
TI  - Evidence for the use of fire at zhoukoudian, china 
AB  - Zhoukoudian is widely regarded as having the oldest reliable evidence for the
      controlled use of fire by humans. A reexamination of the evidence in Layer 10,
      the earliest archaeological horizon in the site, shows that burned and unburned
      bones are present in the same layer with stone tools. However, no ash or charcoal
      remnants could be detected. Hence, although indirect evidence for burning is
      present, there is no direct evidence for in situ burning.

PMID- 9657719
TI  - Design of a 20-amino acid, three-stranded beta-sheet protein.
AB  - A 20-residue protein (named Betanova) forming a monomeric, three-stranded,
      antiparallel beta sheet was designed using a structural backbone template and an
      iterative hierarchical approach. Structural and physicochemical characterization
      show that the beta-sheet conformation is stabilized by specific tertiary
      interactions and that the protein exhibits a cooperative two-state folding
      unfolding transition, which is a hallmark of natural proteins. The Betanova
      molecule constitutes a tractable model system to aid in the understanding of beta
      sheet formation, including beta-sheet aggregation and amyloid fibril formation.

PMID- 9657720
TI  - A small, nonpeptidyl mimic of granulocyte-colony-stimulating factor [see
      commetns].
AB  - A nonpeptidyl small molecule SB 247464, capable of activating granulocyte-colony
      stimulating factor (G-CSF) signal transduction pathways, was identified in a high
      throughput assay in cultured cells. Like G-CSF, SB 247464 induced tyrosine
      phosphorylation of multiple signaling proteins and stimulated primary murine bone
      marrow cells to form granulocytic colonies in vitro. It also elevated peripheral
      blood neutrophil counts in mice. The extracellular domain of the murine G-CSF
      receptor was required for the activity of SB 247464, suggesting that the compound
      acts by oligomerizing receptor chains. The results indicate that a small molecule
      can activate a receptor that normally binds a relatively large protein ligand.

PMID- 9657721
TI  - Infrared MALDI mass spectrometry of large nucleic acids.
AB  - Mass spectrometry has become an increasingly important tool of high accuracy,
      efficiency, and speed for the routine analysis of nucleic acids. To make it
      useful for large-scale sequencing of genomic material as required for example in
      genotyping and clinical diagnosis, it is necessary to find approaches that allow
      the analysis of sequences much larger than the 100 nucleotides currently
      possible. Matrix-assisted laser desorption/ionization (MALDI) mass spectra of
      synthetic DNA, restriction enzyme fragments of plasmid DNA, and RNA transcripts
      up to a size of 2180 nucleotides are reported. The demonstrated mass accuracy of
      1 percent or better and the sample requirement of a few femtomoles or less
      surpass all currently available techniques for the analysis of large nucleic
      acids. DNA and RNA can be analyzed with only a limited investment in sample
      purification.

PMID- 9657722
TI  - Structure of the Escherichia coli RNA polymerase alpha subunit amino-terminal
      domain.
AB  - The 2.5 angstrom resolution x-ray crystal structure of the Escherichia coli RNA
      polymerase (RNAP) alpha subunit amino-terminal domain (alphaNTD), which is
      necessary and sufficient to dimerize and assemble the other RNAP subunits into a
      transcriptionally active enzyme and contains all of the sequence elements
      conserved among eukaryotic alpha homologs, has been determined. The alphaNTD
      monomer comprises two distinct, flexibly linked domains, only one of which
      participates in the dimer interface. In the alphaNTD dimer, a pair of helices
      from one monomer interact with the cognate helices of the other to form an
      extensive hydrophobic core. All of the determinants for interactions with the
      other RNAP subunits lie on one face of the alphaNTD dimer. Sequence alignments,
      combined with secondary-structure predictions, support proposals that a
      heterodimer of the eukaryotic RNAP subunits related to Saccharomyces cerevisiae
      Rpb3 and Rpb11 plays the role of the alphaNTD dimer in prokaryotic RNAP.

PMID- 9657723
TI  - Cell cycle arrest by Vpr in HIV-1 virions and insensitivity to antiretroviral
      agents.
AB  - Expression of human immunodeficiency virus-type 1 (HIV-1) Vpr after productive
      infection of T cells induces cell cycle arrest in the G2 phase of the cell cycle.
      In the absence of de novo expression, HIV-1 Vpr packaged into virions still
      induced cell cycle arrest. Naturally noninfectious virus or virus rendered
      defective for infection by reverse transcriptase or protease inhibitors were
      capable of inducing Vpr-mediated cell cycle arrest. These results suggest a model
      whereby both infectious and noninfectious virions in vivo, such as those
      surrounding follicular dendritic cells, participate in immune suppression.

PMID- 9657724
TI  - Specific covalent labeling of recombinant protein molecules inside live cells.
AB  - Recombinant proteins containing four cysteines at the i, i + 1, i + 4, and i + 5
      positions of an alpha helix were fluorescently labeled in living cells by
      extracellular administration of 4',5'-bis(1,3, 2-dithioarsolan-2-yl)fluorescein.
      This designed small ligand is membrane-permeant and nonfluorescent until it binds
      with high affinity and specificity to the tetracysteine domain. Such in situ
      labeling adds much less mass than does green fluorescent protein and offers
      greater versatility in attachment sites as well as potential spectroscopic and
      chemical properties. This system provides a recipe for slightly modifying a
      target protein so that it can be singled out from the many other proteins inside
      live cells and fluorescently stained by small nonfluorescent dye molecules added
      from outside the cells.

PMID- 9657726
TI  - Growth factors and hematopoietic cell fate. A new feature: controversies in
      hematology 

PMID- 9657725
TI  - Rad53 FHA domain associated with phosphorylated Rad9 in the DNA damage
      checkpoint.
AB  - The Rad53 protein kinase of Saccharomyces cerevisiae is required for checkpoints
      that prevent cell division in cells with damaged or incompletely replicated DNA.
      The Rad9 protein was phosphorylated in response to DNA damage, and phosphorylated
      Rad9 interacted with the COOH-terminal forkhead homology-associated (FHA) domain
      of Rad53. Inactivation of this domain abolished DNA damage-dependent Rad53
      phosphorylation, G2/M cell cycle phase arrest, and increase of RNR3 transcription
      but did not affect replication inhibition-dependent Rad53 phosphorylation. Thus,
      Rad53 integrates DNA damage signals by coupling with phosphorylated Rad9. The
      hitherto uncharacterized FHA domain appears to be a modular protein-binding
      domain.

PMID- 9657727
TI  - Lineage commitment and maturation in hematopoietic cells: the case for extrinsic
      regulation.

PMID- 9657729
TI  - Rebuttal to enver, heyworth, and dexter 

PMID- 9657728
TI  - Do stem cells play dice?

PMID- 9657730
TI  - Rebuttal to metcalf 

PMID- 9657731
TI  - Specific signals generated by the cytoplasmic domain of the granulocyte colony
      stimulating factor (G-CSF) receptor are not required for G-CSF-dependent
      granulocytic differentiation.
AB  - Granulocyte colony-stimulating factor (G-CSF) is the principal growth factor
      regulating the production of neutrophils, yet its role in lineage commitment and
      terminal differentiation of hematopoietic progenitor cells is controversial. In
      this study, we describe a system to study the role of G-CSF receptor (G-CSFR)
      signals in granulocytic differentiation using retroviral transduction of G-CSFR
      deficient, primary hematopoietic progenitor cells. We show that ectopic
      expression of wild-type G-CSFR in hematopoietic progenitor cells supports G-CSF
      dependent differentiation of these cells into mature granulocytes, macrophages,
      megakaryocytes, and erythroid cells. Furthermore, we show that two mutant G-CSFR
      proteins, a truncation mutant that deletes the carboxy-terminal 96 amino acids
      and a chimeric receptor containing the extracellular and transmembrane domains of
      the G-CSFR fused to the cytoplasmic domain of the erythropoietin receptor, are
      able to support the production of morphologically mature, chloroacetate esterase
      positive, Gr-1/Mac-1-positive neutrophils in response to G-CSF. These results
      demonstrate that ectopic expression of the G-CSFR in hematopoietic progenitor
      cells allows for multilineage differentiation and suggest that unique signals
      generated by the cytoplasmic domain of the G-CSFR are not required for G-CSF
      dependent granulocytic differentiation.

PMID- 9657733
TI  - Transgenic mice for MTCP1 develop T-cell prolymphocytic leukemia.
AB  - T-cell prolymphocytic leukemia (T-PLL) is a rare form of mature T-cell leukemia
      associated with chromosomal rearrangements implicating MTCP1 or TCL1 genes. These
      genes encode two homologous proteins, p13(MTCP1) and p14(TCL1), which share no
      similarity with other known protein. To determine the oncogenic role of MTCP1,
      mice transgenic for MTCP1 under the control of CD2 regulatory regions (CD2-p13
      mice) were generated. No abnormality was detected during the first year after
      birth. A late effect of the transgene was searched for in a cohort of 48 CD2-p13
      mice aged 15 to 20 months, issued from 3 independent founders. Lymphoid
      hemopathies, occurring in the three transgenic lines, were characterized by
      lymphoid cells with an irregular nucleus, a unique and prominent nucleolus,
      condensed chromatin, a basophilic cytoplasm devoid of granules, and an
      immunophenotype of mature T cells. The molecular characterization of Tcrb
      rearrangements demonstrated the monoclonal origin of these populations.
      Histopathological analysis of the cohort demonstrated early splenic and hepatic
      infiltrations, whereas lymphocytosis and medullar infiltrations were found
      infrequently. The engraftment of these proliferations in H2-matched animals
      demonstrated their malignant nature. Cumulative incidence of the disease at 20
      months was 100%, 50%, and 21% in F3, F4, and F7 lines, respectively, and null in
      the control group. The level of expression of the transgene, as estimated by
      Western blotting in the transgenic lines correlated with the tumoral incidence,
      with the highest expression of p13(MTCP1) being found in F3 mice. CD2-p13
      transgenic mice developed an hemopathy similar to human T-PLL. These data
      demonstrate that p13(MTCP1) is an oncoprotein and that CD2-p13 transgenic mice
      represent the first animal model for mature T-PLL.

PMID- 9657732
TI  - Evidence for circulating bone marrow-derived endothelial cells.
AB  - It has been proposed that hematopoietic and endothelial cells are derived from a
      common cell, the hemangioblast. In this study, we demonstrate that a subset of
      CD34(+) cells have the capacity to differentiate into endothelial cells in vitro
      in the presence of basic fibroblast growth factor, insulin-like growth factor-1,
      and vascular endothelial growth factor. These differentiated endothelial cells
      are CD34(+), stain for von Willebrand factor (vWF), and incorporate acetylated
      low-density lipoprotein (LDL). This suggests the possible existence of a bone
      marrow-derived precursor endothelial cell. To demonstrate this phenomenon in
      vivo, we used a canine bone marrow transplantation model, in which the marrow
      cells from the donor and recipient are genetically distinct. Between 6 to 8
      months after transplantation, a Dacron graft, made impervious to prevent
      capillary ingrowth from the surrounding perigraft tissue, was implanted in the
      descending thoracic aorta. After 12 weeks, the graft was retrieved, and cells
      with endothelial morphology were identified by silver nitrate staining. Using the
      di(CA)n and tetranucleotide (GAAA)n repeat polymorphisms to distinguish between
      the donor and recipient DNA, we observed that only donor alleles were detected in
      DNA from positively stained cells on the impervious Dacron graft. These results
      strongly suggest that a subset of CD34+ cells localized in the bone marrow can be
      mobilized to the peripheral circulation and can colonize endothelial flow
      surfaces of vascular prostheses.

PMID- 9657734
TI  - Mutations in the E-domain of RAR portion of the PML/RAR chimeric gene may confer
      clinical resistance to all-trans retinoic acid in acute promyelocytic leukemia.
AB  - The binding of all-trans retinoic acid (ATRA) to the ligand-binding region in the
      E-domain of retinoic acid receptor-alpha modifies the transcriptional activity of
      RARalpha protein. ATRA probably induces differentiation of acute promyelocytic
      leukemia (APL) cells by binding to the E-domain of the RARalpha portion (RARalpha
      /E-domain) of PML/RARalpha chimeric protein. Therefore, molecular alteration in
      the RARalpha /E-domain of the chimeric gene is one mechanism by which patients
      with APL may acquire resistance to ATRA therapy. In this study using reverse
      transcription-polymerase chain reaction and single-strand conformation
      polymorphism, DNA segments amplified from the RARalpha /E-domain in fresh APL
      cells of 23 APL patients (8 males and 15 females from 4 to 76 years of age) were
      screened for mutations. Of those patients, 3 patients (1 with de novo and 2 with
      relapse) had clinical resistance to ATRA therapy. We found mutations in the
      RARalpha /E-domain of PML/RARalpha chimeric gene exclusively in the 2 patients
      who exhibited ATRA-resistance at relapse, whereas the mutations were not detected
      at their initial onset. Interestingly, these patients received a prolonged or
      intermittent administration of ATRA before relapse with ATRA-resistance. The
      mutations lead to the change of amino acid in the ligand-binding region of
      RARalpha /E-domain, Arg272Gln, or Met297Leu according to the amino acid sequence
      of RARalpha, respectively. Further study demonstrated that the in vitro ligand
      dependent transcriptional activity of the mutant PML/RARalpha protein was
      significantly decreased as compared with that of wild-type PML/RARalpha. These
      findings suggest that mutations in the RARalpha /E-domain of the PML/RARalpha
      chimeric gene may confer clinical resistance to ATRA therapy in patients with
      APL.

PMID- 9657735
TI  - Loss of function of the homeobox gene Hoxa-9 perturbs early T-cell development
      and induces apoptosis in primitive thymocytes.
AB  - Hox homeobox genes play a crucial role in specifying the embryonic body pattern.
      However, a role for Hox genes in T-cell development has not been explored. The
      Hoxa-9 gene is expressed in normal adult and fetal thymuses. Fetal thymuses of
      mice homozygous for an interruption of the Hoxa-9 gene are one eighth normal size
      and have a 25-fold decrease in the number of primitive thymocytes expressing the
      interleukin-2 receptor (IL-2R, CD25). Progression to the double positive
      (CD4+CD8+) stage is dramatically retarded in fetal thymic organ cultures. This
      aberrant development is associated with decreased amounts of intracellular CD3
      and T-cell receptor beta (TCRbeta) and reduced surface expression of IL-7R and E
      cadherin. Mutant thymocytes show a significant increase in apoptotic cell death
      and premature downregulation of bcl-2 expression. A similar phenotype is seen in
      primitive thymocytes from adult Hoxa-9-/- mice and from mice transplanted with
      Hoxa-9-/- marrow. Hoxa-9 appears to play a previously unsuspected role in T-cell
      ontogeny by modulating cell survival of early thymocytes and by regulating their
      subsequent differentiation.

PMID- 9657736
TI  - Association between pretransplant interferon-alpha and outcome after unrelated
      donor marrow transplantation for chronic myelogenous leukemia in chronic phase.
AB  - Treatment options for patients diagnosed with chronic myelogenous leukemia (CML)
      in chronic phase (CP) who lack a suitable related donor for marrow
      transplantation include hydroxyurea, interferon-alpha (IFN-alpha), or
      transplantation from an unrelated donor (URD). Most studies support the view that
      treatment with IFN-alpha results in prolonged survival compared with hydroxyurea
      therapy. Some patients are offered URD transplantation as a second-line
      treatment; however, the impact of pretransplant IFN-alpha on the outcome of URD
      transplantation is uncertain. To address this question, we evaluated the effect
      of pretransplant IFN-alpha therapy in 184 patients undergoing URD transplantation
      for CML in CP at a single center. Of the 184 patients, 114 did not receive IFN
      alpha, whereas 22, 23, and 25 patients received IFN-alpha for, respectively, 1 to
      5, 6 to 12, and more than 12 months before transplant. Pretransplant IFN-alpha
      therapy administered for > or = 6 months was associated with an increased risk of
      severe (grades III-IV) acute graft-versus-host disease (GVHD; relative risk [RR],
      3.0; 95% confidence interval [CI], 1.4 to 6.2; P = .004) and mortality (RR, 2. 1;
      95% CI, 1.3 to 3.5; P = .003) relative to less than 6 months or no IFN-alpha
      therapy. Increased mortality occurred between 100 and 365 days after transplant
      (P = .005), was limited to patients with severe acute GVHD, and was due to
      chronic GVHD refractory to immunosuppressive therapy. Other variables associated
      with mortality included HLA-DRB1 or DQB1 (but not HLA-A or B) mismatched donors,
      age greater than 50 years, weight > or = 110% of ideal body weight, and the
      absence of cytomegalovirus (CMV) or fungal prophylaxis. For patients treated with
      IFN-alpha for less than 6 months before transplant, who were < or = 50 years of
      age, received a HLA-A, B, DRB1, and DQB1 matched URD transplant, and received CMV
      and fungal prophylaxis after transplant (n = 48), survival was 87% +/- 5% at 5
      years. These data provide a rationale for immediate transplantation in preference
      to extended treatment with IFN-alpha when the patient is < or = 50 years of age
      and has an HLA-compatible unrelated volunteer donor.

PMID- 9657737
TI  - Blood dendritic cells from myeloma patients are not infected with Kaposi's
      sarcoma-associated herpesvirus (KSHV/HHV-8).
AB  - In recent studies, the sequence of Kaposi's sarcoma-associated herpes virus
      (KSHV) or human herpes virus-8 (HHV-8) was detected in dendritic cells (DC) of
      patients with multiple myeloma (MM). A concern was raised whether there is an
      causal association between the viral infection and development of these tumors.
      In the present study, we have examined DC generated from blood adherent cells
      from 8 Swedish MM patients at different clinical stages and 2 patients with
      monoclonal gammopathy of undetermined significance. In addition, 6 myeloma cell
      lines and bone marrow cells from 2 MM patients were also studied. By polymerase
      chain reaction (PCR), including nested PCR, no virus DNA was demonstrable in the
      patients' DC or in myeloma cell lines or fresh bone marrow cells. Moreover, no
      antibody against KSHV was found in the serum of these 10 patients. Thus, our
      results indicate that blood-derived DC of MM patients in Sweden usually are not
      infected with KSHV/HHV-8. This study also suggests that KSHV/HHV-8 is not
      regularly associated with MM and consequently does not play a primary role in the
      pathogenesis of these tumors.

PMID- 9657738
TI  - A risk model for thrombocytopenia requiring platelet transfusion after cytotoxic
      chemotherapy.
AB  - Severe thrombocytopenia is a rare but life-threatening side effect of cytotoxic
      chemotherapy for which risk factors are not well known. Our objective was to
      delineate a risk model for chemotherapy-induced thrombocytopenia requiring
      platelet transfusions in cancer patients. Univariate and multivariate analysis of
      risk factors for chemotherapy-induced thrombocytopenia requiring platelet
      transfusions were performed on the cohort of the 1,051 patients (CLB 1996)
      treated with chemotherapy in the Department of Medicine of the Centre Leon Berard
      (CLB) in 1996. In univariate analysis, performance status (PS) greater than 1,
      platelet count less than 150, 000/microL at day 1 (d1) before the initiation of
      chemotherapy, d1 lymphocyte count < or = 700/microL, d1 polymorphonuclear
      leukocyte count less than 1,500/microL, and the type of chemotherapy (high risk v
      others) were significantly associated (P < .01) with an increased risk of severe
      thrombocytopenia requiring platelet transfusions. Using logistic regression, d1
      platelet count less than 150,000/microL (odds ratio [OR], 4.3; 95% confidence
      interval [CI], 1.9 to 9.6), d1 lymphocyte counts < or = 700/microL (OR, 3.37; 95%
      CI, 1.77 to 6.4), the type of chemotherapy (OR, 3.38; 95% CI, 1.77 to 6.4), and
      PS greater than 1 (OR, 2.23; 95% CI, 1.22 to 4.1) were identified as independent
      risk factors for platelet transfusions. The observed incidences of platelet
      transfusions were 45%, 13%, 7%, and 1.5% for patients with > or = 3, 2, 1, or 0
      risk factors, respectively. This model was then tested in 3 groups of patients
      treated with chemotherapy used as validation samples: (1) the series of 340
      patients treated in the CLB in the first 6 months of 1997, (2) the prospective
      multicentric cohort of 321 patients of the ELYPSE 1 study, and (3) the series of
      149 patients with non-Hodgkin's lymphoma treated in the CLB within prospective
      phase III trials (1987 to 1995). In these 3 groups, the observed incidences of
      platelet transfusions in the above-defined risk groups did not differ
      significantly (P > .1) from those calculated in the model. This risk index could
      be useful to identify patients at high risk for chemotherapy-induced
      thrombocytopenia requiring platelet transfusions.

PMID- 9657739
TI  - Early intensification of intrathecal chemotherapy virtually eliminates central
      nervous system relapse in children with acute lymphoblastic leukemia.
AB  - Central nervous system (CNS) relapse has been an obstacle to uniformly successful
      treatment of childhood acute lymphoblastic leukemia (ALL) for many years. We
      therefore intensified intrathecal chemotherapy (simultaneously administered
      methotrexate, hydrocortisone, and cytarabine) for 165 consecutive children with
      newly diagnosed ALL enrolled in Total Therapy Study XIIIA from December 1991 to
      August 1994. The 64 patients (39%) who had 1 or more blast cells in
      cytocentrifuged preparations of cerebrospinal fluid at diagnosis, with or without
      associated higher-risk features, received additional doses of intrathecal
      chemotherapy during remission induction and the first year of continuation
      treatment. Patients with higher-risk leukemia, regardless of cerebrospinal fluid
      findings, also received additional doses of intrathecal chemotherapy during the
      first year of continuation treatment. Cranial irradiation was reserved for
      patients with higher-risk leukemia (22% of the total). The 5-year cumulative risk
      of an isolated CNS relapse among all 165 patients was 1.2% (95% confidence
      interval, 0% to 2.9%), whereas that of any CNS relapse was 3.2% (0. 4% to 6.0%).
      The probability of surviving for 5 years without an adverse event of any type was
      80.2% +/- 9.2% (SE). Our results suggest that early intensification of
      intrathecal chemotherapy will reduce the risk of CNS relapse to a very low level
      in children with ALL, securing a higher event-free survival rate overall.

PMID- 9657740
TI  - Granulocyte-macrophage colony-stimulating factor rescues TF-1 leukemia cells from
      ionizing radiation-induced apoptosis through a pathway mediated by protein kinase
      Calpha.
AB  - Protein kinase C (PKC) activity has a recognized role in mediating apoptosis.
      However, the role of individual PKC isoforms in apoptosis is poorly defined.
      Therefore, we investigated the translocation of individual PKC isoforms during
      radiation-induced apoptosis with and without rescue from apoptosis by granulocyte
      macrophage colony-stimulating factor (GM-CSF) in the human erythroleukemia cell
      line TF-1. PKCalpha was translocated from the particulate to cytosolic fraction
      of TF-1 cells within 5 minutes of treatment with apoptosis-inducing levels of
      ionizing radiation. However, this postirradiation translocation did not occur
      when cells were rescued from apoptosis by GM-CSF. Furthermore, treatment of cells
      with Go 6976, an inhibitor of classical PKC isoforms, abrogated the rescue effect
      of GM-CSF. The calcium-independent novel PKC isoform, PKCalpha appeared to be
      degraded in both the particulate and cytosolic fractions of TF-1 cells after
      treatment with apoptosis-inducing levels of ionizing radiation in either the
      presence or absence of GM-CSF rescue. Levels of ceramide, a lipid mediator of
      apoptosis, were measured at 2, 4, 8, 10, and 60 minutes after treatment with
      ionizing radiation and were substantially reduced in TF-1 cells rescued from
      apoptosis by GM-CSF compared with apoptotic TF-1 cells. The largest decrease in
      ceramide production seen was at 4 minutes postirradiation, with a 46% reduction
      in ceramide levels in TF-1 cells rescued from apoptosis by GM-CSF compared with
      those in apoptotic TF-1 cells. Because ceramide has been shown to affect PKCalpha
      subcellular distribution, these data implicate a role for ceramide in mediating
      the rapid postirradiation translocation and inhibition of PKCalpha in TF-1 cells
      not rescued from apoptosis by GM-CSF. Expression of the antiapoptotic protein Bcl
      2 doubled in TF-1 cells rescued from apoptosis by GM-CSF, but did not increase in
      unrescued cells. Our findings suggest that activated PKCalpha and increased
      expression of Bcl-2 after gamma irradiation determine survival in TF-1 cells
      rescued from apoptosis with GM-CSF and that PKCalpha plays a role in mediating
      signals involved in sensing cellular damage and/or regulation of cell damage
      repair.

PMID- 9657741
TI  - The hyperresponsiveness of cells expressing truncated erythropoietin receptors is
      contingent on insulin-like growth factor-1 in fetal calf serum.
AB  - We demonstrate herein that the well documented hyperresponsiveness to
      erythropoietin (Epo) of Ba/F3 cells expressing C-terminal truncated
      erythropoietin receptors (EpoRs) is contingent on these cells being in fetal calf
      serum (FCS). In the absence of FCS, their Epo-induced proliferation is far poorer
      than Ba/F3 cells expressing wild-type (WT) EpoRs. This hyporesponsiveness in the
      absence of serum is also seen in DA-3 cells expressing these truncated EpoRs. In
      fact, long-term proliferation studies performed in the absence of serum show that
      even at saturating concentrations of Epo, Ba/F3 cells expressing these truncated
      receptors die via apoptosis, while cells bearing WT EpoRs do not, and this
      programmed cell death correlates with an inability of Epo-stimulated Ba/F3 cells
      expressing truncated EpoRs to induce the tyrosine phosphorylation of MAPK and the
      activation of p70(S6K). Using neutralizing antibodies to insulin-like growth
      factor (IGF)-1, we show that a major non-Epo factor in FCS that contributes to
      the hyperresponsive phenotype of Ba/F3 cells expressing truncated EpoRs is IGF-1.
      Our results suggest that the Epo-hypersensitivity of truncated EpoR expressing
      Ba/F3 cells is due to the combined effects of these EpoRs not possessing a
      binding site for the negative regulator, SHP-1, and the triggering of
      proliferation-inducing/apoptosis-inhibiting cascades, lost through EpoR
      truncation, by IGF-1.

PMID- 9657742
TI  - Role of GATA-1 in proliferation and differentiation of definitive erythroid and
      megakaryocytic cells in vivo.
AB  - To elucidate the contributions of GATA-1 to definitive hematopoiesis in vivo, we
      have examined adult mice that were rendered genetically defective in GATA-1
      synthesis (Takahashi et al, J Biol Chem 272:12611, 1997). Because the GATA-1 gene
      is located on the X chromosome, which is randomly inactivated in every cell,
      heterozygous females can bear either an active wild-type or mutant (referred to
      as GATA-1.05) GATA-1 allele, consequently leading to variable anemic severity.
      These heterozygous mutant mice usually developed normally, but they began to die
      after 5 months. These affected animals displayed marked splenomegaly, anemia, and
      thrombocytopenia. Proerythroblasts and megakaryocytes massively accumulated in
      the spleens of the heterozygotes, and we showed that the neomycin resistance gene
      (which is the positive selection marker in ES cells) was expressed profusely in
      the abnormally abundant cells generated in the GATA-1.05 mutant females. We also
      observed hematopoiesis outside of the bone marrow in the affected mutant mice.
      These data suggest that a small number of GATA-1.05 mutant hematopoietic
      progenitor cells begin to proliferate vigorously during early adulthood, but
      because the cells are unable to terminally differentiate, this leads to
      progenitor proliferation in the spleen and consequently death. Thus, GATA-1 plays
      important in vivo roles for directing definitive hematopoietic progenitors to
      differentiate along both the erythroid and megakaryocytic pathways. The GATA-1
      heterozygous mutant mouse shows a phenotype that is analogous to human
      myelodysplastic syndrome and thus may serve as a useful model for this disorder.

PMID- 9657743
TI  - Erythropoietin induces tyrosine phosphorylation of Jak2, STAT5A, and STAT5B in
      primary cultured human erythroid precursors.
AB  - We examined signaling by erythropoietin in highly purified human colony forming
      unit-erythroid cells, generated in vitro from CD34(+) cells. We found that
      erythropoietin induces tyrosine phosphorylation of Jak2, STAT5A, and STAT5B.
      Tyrosine phosphorylation of Jak2 reaches a peak around 10 minutes after
      stimulation and is maximum at 5 U/mL of erythropoietin. Tyrosine phosphorylation
      of STAT5 is accompanied by the translocation of activated STAT5 to the nucleus as
      shown by electrophoretic mobility shift assay (EMSA) using 32Pi-labeled STAT5
      binding site in the beta-casein promoter. Tyrosine phosphorylation STAT1 or STAT3
      was not detected in human erythroid precursors after stimulation with
      erythropoietin. Crkl, an SH2/SH3 adapter protein, becomes coimmunoprecipitated
      specifically with STAT5 from erythropoietin-stimulated erythroid cells; although
      it was shown to become associated with c-Cbl in the studies using cell lines.
      Thus, human erythroid precursors can be expanded in vitro in sufficient numbers
      and purity to allow its usage in signal transduction studies. This report sets a
      basis for further studies on signaling in primary cultured human erythroid
      precursors, which in turn contribute to our better understanding in the
      differentiation processes of erythrocytes and their precursors.

PMID- 9657744
TI  - Thrombopoietin promotes the survival of murine hematopoietic long-term
      reconstituting cells: comparison with the effects of FLT3/FLK-2 ligand and
      interleukin-6.
AB  - The effects of thrombopoietin (TPO; c-mpl ligand), FLT3/FLK-2 ligand (FL), and
      interleukin-6 (IL-6) on the survival of murine hematopoietic long-term
      reconstituting cells (LTRC) were studied by using lineage-negative, Sca-1
      positive, c-kit-positive (Lin-Sca-1(+)c-kit+) marrow cells from 5-fluorouracil
      treated mice. We tested the ability of these cytokines to maintain the viability
      of LTRC by transplanting the cultured cells to lethally irradiated Ly-5 congenic
      mice together with compromised marrow cells. As a single agent, only TPO could
      maintain the LTRC. Neither IL-6 nor FL was effective by itself, but they acted
      synergistically to maintain the LTRC. We examined whether the maintenance of LTRC
      by these cytokines was due to the survival of stem cells or was the result of
      active cell divisions and self-renewal. To monitor cell division, we used
      membrane dye PKH26. Enriched cells were stained with PKH26 on day 0 and incubated
      in suspension culture with TPO or with IL-6 and FL for 7 days. On day 7,
      PKH26(low) and PKH26(high) cells were prepared by sorting and their in vivo
      reconstituting abilities were tested by transplantation into lethally irradiated
      Ly-5 congenic mice together with compromised marrow cells. PKH26(high)
      populations cultured with both TPO alone and the combination of IL-6 and FL
      showed greater reconstitution activity than that of PKH26(low) populations. These
      data indicate that TPO alone and the combination of IL-6 and FL can support the
      survival of stem cells without stimulating their active cell proliferation.

PMID- 9657745
TI  - A novel function of Stat1 and Stat3 proteins in erythropoietin-induced erythroid
      differentiation of a human leukemia cell line.
AB  - We recently determined that erythropoietin (EPO) activates 3 members of the
      signal transducer and activator of transcription (STAT) family, Stat1alpha,
      Stat3, and Stat5, in the human EPO-dependent cell lines, UT-7 and UT-7/EPO
      (Kirito et al, J Biol Chem 272:16507, 1997). In addition, we have shown that
      Stat1alpha, but not Stat3, is involved in EPO-induced cellular proliferation. In
      this study, we examined the roles of Stat1alpha and Stat3 in EPO-induced
      erythroid differentiation. UT-7/GM was used as a model system, because this cell
      line can differentiate into erythroid-lineage cells with EPO treatment (Komatsu
      et al, Blood 89:4021, 1997). We found that EPO did not activate Stat1alpha or
      Stat3 in UT-7/GM cells. Transfection experiments showed that both Stat1alpha and
      Stat3 inhibited the induction by EPO of gamma-globin and erythroid-specific 5
      aminolevulinate synthetase transcripts, resulting in a reduction of the
      percentage of hemoglobin-positive cells. Dominant negative forms of Stat1alpha or
      Stat3 promoted the EPO-induced erythroid differentiation of UT-7/GM cells, even
      in the presence of granulocyte-macrophage colony-stimulating factor, although
      this cytokine never induced erythroid differentiation of the parent UT-7/GM cells
      with or without EPO. A cell cycle analysis showed that the constitutive
      activation of Stat1alpha, but not Stat3, shortened the period of G0/G1
      prolongation caused by EPO stimulation. Taken together, our data suggest that
      Stat1alpha and Stat3 act as negative regulators in EPO-induced erythroid
      differentiation. Specifically, Stat1alpha may activate a cell cycle-associated
      gene(s), leading to the entry of cells into the cell cycle.

PMID- 9657746
TI  - The induction of megakaryocyte differentiation is accompanied by selective Ser133
      phosphorylation of the transcription factor CREB in both HEL cell line and
      primary CD34+ cells.
AB  - The addition of thrombopoietin (TPO) to HEL cells, cultured in a chemically
      defined serum-free medium, induced a rapid and dose-dependent phosphorylation of
      the transcription factor CREB on serine133 (PSer133), as detected by Western blot
      analysis. TPO also significantly increased the transactivation of CRE-dependent
      promoter, as determined in transient transfection experiments. On the other hand,
      neither erythropoietin (Epo; 1 to 10 U) nor hemin (10 (-7) mol/L) were able to
      significantly stimulate CREB-PSer133 or to activate CRE-promoter in HEL cells.
      Although pharmacological inhibitors of protein kinase C (chelerytrine and BIM)
      and protein kinase A (H-89) failed to block the TPO-mediated CREB
      phosphorylation, a specific inhibitor of the mitogen-activated protein kinases
      (PD98059) completely blocked the ability of TPO to stimulate CREB-PSer133.
      Moreover, PD98059 significantly decreased the ability of TPO to upregulate the
      surface expression of the alphaIIIbbeta3 megakaryocytic marker in HEL cells. In
      parallel, primary CD34+ hematopoietic cells were seeded in liquid cultures
      supplemented with 100 ng/mL of TPO and examined by immunofluorescence for the
      coexpression of alphaIIIbbeta3 and CREB-PSer133 at various time points. High
      levels of nuclear CREB-PSer133 were unequivocally demonstrated in alphaIIIbbeta3+
      cells, including morphologically recognizable megakaryocytes. Taken together,
      these data suggest that CREB plays a role in modulating the expression of genes
      critical for megakaryocyte differentiation and that the TPO-mediated CREB
      phosphorylation seems to be regulated via mitogen-activated protein kinases.

PMID- 9657747
TI  - A novel Asn344 deletion in the core domain of coagulation factor XIII A subunit:
      its effects on protein structure and function.
AB  - In this study a previously undescribed 3 bp deletion, AAT1030-1032, in the factor
      XIII A subunit gene, has been detected in a Thai patient. The inframe deletion
      results in the translation of a factor XIII A subunit that lacks Asn344. This is
      the first inframe deletion to be identified in the factor XIII A subunit gene
      because six previously reported deletions have all caused frameshifts. The
      deletion has been introduced into a factor XIII A subunit cDNA and the deleted
      polypeptide expressed in yeast. The mRNA encoding the mutant enzyme appears to
      have normal stability but the translated protein is subject to premature
      degradation. In addition, the mutated enzyme exhibited very little
      transglutaminase activity compared with the wild-type enzyme. Structural modeling
      of the deleted enzyme suggests that the absence of Asn344 would have a potent
      impact on the catalytic activity by reorienting the residues associated with the
      catalytic center. Thus, the Asn344 deletion strongly confirms the significance of
      the residues surrounding the catalytic center of the factor XIII A subunit.

PMID- 9657748
TI  - In vivo expression of murine platelet glycoprotein Ibalpha.
AB  - We have performed a systematic in vivo evaluation of gene expression for the
      glycoprotein (GP) Ibalpha subunit of the murine platelet adhesion receptor, GP Ib
      IX-V. This study is warranted by in vitro observations of human GP Ibalpha
      expression in cells of nonhematopoietic lineage and reports of regulation of the
      GP Ibalpha gene by cytokines. However, an in vivo role for a GP Ib-IX-V receptor
      has not been established beyond that described for normal megakaryocyte/platelet
      physiology and hemostasis. Our Northern analysis of mouse organs showed high
      levels of GP Ibalpha mRNA in bone marrow with a similar expression pattern
      recapitulated in mice containing a luciferase transgene under the control of the
      murine GP Ibalpha promoter. Consistently high levels of luciferase activity were
      observed in the two hematopoietic organs of mice, bone marrow (1,400 relative
      light units/microg of protein [RLUs]) and spleen (500 RLUs). Reproducible, but
      low-levels of luciferase activity were observed in heart, aorta, and lung (30 to
      60 RLUs). Among circulating blood cells, the luciferase activity was exclusively
      localized in platelets. No increase in GP Ibalpha mRNA or luciferase activity was
      observed after treatment of mice with lipopolysaccharides (LPS) or tumor necrosis
      factor-alpha (TNF-alpha). We conclude the murine GP Ibalpha promoter supports a
      high level of gene expression in megakaryocytes and can express heterologous
      proteins allowing an in vivo manipulation of platelet-specific proteins in the
      unique environment of a blood platelet.

PMID- 9657749
TI  - Mechanism and kinetics of factor VIII inactivation: study with an IgG4 monoclonal
      antibody derived from a hemophilia A patient with inhibitor.
AB  - The development of an immune response towards factor VIII (fVIII) remains a major
      complication for hemophilia A patients receiving fVIII infusions. The design of a
      specific therapy to restore unresponsiveness to fVIII has been hampered by the
      diversity of the anti-fVIII antibody. Molecular analysis of the specific immune
      response is therefore required. To this end, we have characterized an fVIII
      specific human IgG4kappa monoclonal antibody (BO2C11) produced by a cell line
      derived from the memory B-cell repertoire of a hemophilia A patient with
      inhibitor. BO2C11 recognizes the C2 domain of fVIII and inhibits its binding to
      both von Willebrand factor (vWF) and phospholipids. It completely inhibits the
      procoagulant activity of native and activated fVIII, with a specific activity of
      approximately 7,000 Bethesda units/mg. vWF reduces the rate of fVIII inactivation
      by BO2C11. The antibody-fVIII association rate constant (kass approximately 7.4 x
      10(5) M-1 s-1) is eightfold lower than that for vWF-fVIII association, whereas
      its dissociation rate constant (kdiss < or = 1 x 10(-5) s-1) is 100-fold lower
      than that for the vWF-fVIII complex, which suggests that BO2C11 almost
      irreversibly neutralizes fVIII after its dissociation from vWF. BO2C11 is the
      first human monoclonal anti-fVIII IgG antibody that has been isolated and allows
      the study of fVIII inactivation at the molecular level.

PMID- 9657750
TI  - Platelet-endothelial cell interactions during ischemia/reperfusion: the role of P
      selectin.
AB  - Growing evidence supports a pathophysiological role for platelets during the
      manifestation of postischemic reperfusion injury; in the current study, we
      investigated the nature and the molecular determinants of platelet-endothelial
      cell interactions induced by ischemia/reperfusion (I/R). Platelet-endothelium and
      leukocyte-endothelium interactions after 1 hour of ischemia were monitored in
      vivo within mouse small intestine. By intravital fluorescence microscopy, we
      observed that platelets, like leukocytes, roll along or firmly adhere to
      postischemic microvascular endothelial cells. In contrast, few leukocyte
      endothelial cell interactions were detected in sham-operated controls. Monoclonal
      antibodies against P-selectin significantly attenuated platelet rolling and
      adherence in response to I/R. To identify whether platelet or endothelial P
      selectin plays the major role in mediating postischemic platelet-endothelial cell
      interactions, P-selectin-deficient or wild-type platelets were transfused into
      wild-type or P-selectin-deficient mice, respectively. Whereas platelets lacking P
      selectin rolled along or adhered to postischemic wild-type endothelium,
      interactions between wild-type platelets with mutant endothelium were nearly
      absent, indicating that I/R-induced platelet-endothelium interactions are
      dependent on the expression of P-selectin by endothelial cells. Concomitantly, P
      selectin expression in the intestinal microvasculature was enhanced in response
      to I/R, whereas no upregulation of P-selectin was observed on circulating
      platelets. In summary, we provide first in vivo evidence that platelets
      accumulate in the postischemic microvasculature early after reperfusion via P
      selectin-ligand interactions. Platelet recruitment and subsequent activation
      might play an important role in the pathogenesis of I/R injury.

PMID- 9657751
TI  - High prevalence of serum cryoglobulins in multitransfused hemophilic patients
      with chronic hepatitis C.
AB  - The prevalence, clinical relevance, and risk factors of serum cryoglobulins in
      hemophilic patients with chronic hepatitis C virus (HCV) infection are unknown.
      We studied 135 consecutive hemophilic patients (median age, 31 years; range, 10
      to 69 years) with chronic hepatitis C, exposed to the virus for 10 to 41 years. A
      total of 67 patients were coinfected with the human immunodeficiency virus (HIV),
      and 3 (2%) had signs of cirrhosis. Serum samples were tested for the presence of
      cryoglobulins, hepatitis B virus (HBV) markers, including HBV-DNA by
      hybridization assay, and antibody to HCV by enzyme immunoassay (EIA). Serum HCV
      RNA was tested by polymerase chain reaction and typed with a hybridization
      technique. Samples were also tested for antitissue antibodies, immunoglobulins,
      rheumatoid factor, and C3 and C4 proteins of complement. Forty-two hemophiliacs
      (31%) circulated cryoglobulins (median levels, 166 mg/L; range, 66 to 480)
      predominantly type III (62%; and 29% type II). None of the patients had clinical
      signs or symptoms of systemic vasculitis. Cryoglobulinemic patients had more
      often serum HCV-RNA (95% v 80%, P < .05), rheumatoid factor (20% v 6%, P < .05),
      higher levels of IgG (2,354 +/- 682 mg/dL v 1,928 +/- 557 mg/dL, P < .0005) and
      IgM (323 +/- 226 mg/dL v 244 +/- 243 mg/dL, P < .05), and lower levels of serum
      C4 (19 +/- 8 mg/dL v 24 +/- 8 mg/dL, P < .05) than patients without
      cryoglobulins. The risk of producing cryoglobulins was greater for 114 patients
      circulating HCV-RNA than for 21 nonviremic patients (odds ratio [OR] = 4.9, 95%
      confidence interval [CI] = 1.1 to 22.0) and for the 31 patients with longer
      exposure to HCV (more than 26 years) than for the 24 patients with shorter (17
      years or less) exposure (OR = 4.4 95% CI = 1.1 to 18.0). In conclusion a large
      number of multitransfused hemophiliacs with chronic HCV infection circulated
      serum cryoglobulins but none had clinical signs or symptoms of vasculitis. The
      risk of developing cryoglobulins parallels the duration of exposure to HCV.

PMID- 9657752
TI  - Expression of P-selectin on hepatic endothelia and platelets promoting neutrophil
      removal by liver macrophages.
AB  - The role of P-selectin on polymorphonuclear leukocyte (PMN) adhesion-induced PMN
      elimination in the liver is unclear. Our objectives were to show the expression
      and distribution of P-selectin in rat liver, as well as to evaluate the changes
      in the modulation of the expression of P-selectin and its role in the
      accumulation and sequestration of PMNs. The intravenous administration of
      endotoxin markedly increased the expression of P-selectin on the venous and
      sinusoidal endothelial cells, as well as on the platelets trapped in the liver.
      Its expression peaked at 6 hours postinjection and was associated with a rapid
      increase in the aggregation and elimination of PMNs in the hepatic sinusoids.
      Combined treatment with an antibody to P-selectin or with low molecular weight
      heparin, a P-selectin antagonist, blocked the P-selectin, significantly reduced
      the arrest of PMNs, and delayed their removal in the liver. Pretreatment with
      gadolinium chloride inhibited phagocytosis of PMNs by the Kupffer cells,
      decreased the expression of P-selectin, and limited the hepatic accumulation of
      PMNs. Thus, P-selectin played a role in accumulation and elimination of PMNs from
      the liver. Results also suggest that activated Kupffer cells can modulate the
      expression of P-selectin in the liver and influence the homeostasis of PMNs in
      the circulation during acute inflammation.

PMID- 9657753
TI  - Binding of factor VIII to von willebrand factor is enabled by cleavage of the von
      Willebrand factor propeptide and enhanced by formation of disulfide-linked
      multimers.
AB  - von Willebrand factor (vWF) is a multimeric adhesive glycoprotein with one factor
      VIII binding site/subunit. Prior reports suggest that posttranslational
      modifications of vWF, including formation of N-terminal intersubunit disulfide
      bonds and subsequent cleavage of the propeptide, influence availability and/or
      affinity of factor VIII binding sites. We found that deletion of the vWF
      propeptide produced a dimeric vWF molecule lacking N-terminal intersubunit
      disulfide bonds. This molecule bound fluorescein-labeled factor VIII with sixfold
      lower affinity than multimeric vWF in an equilibrium flow cytometry assay
      (approximate KDs, 5 nmol/L v 0.9 nmol/L). Coexpression of propeptide-deleted vWF
      with the vWF propeptide in trans yielded multimeric vWF that displayed increased
      affinity for factor VIII. Insertion of an alanine residue at the N-terminus of
      the mature vWF subunit destroyed binding to factor VIII, indicating that the
      native mature N-terminus is required for factor VIII binding. The requirement for
      vWF propeptide cleavage was shown by (1) a point mutation of the vWF propeptide
      cleavage site yielding pro-vWF that was defective in factor VIII binding and (2)
      correlation between efficiency of intracellular propeptide cleavage and factor
      VIII binding. Furthermore, in a cell-free system, addition of the propeptide
      cleaving enzyme PACE/furin enabled factor VIII binding in parallel with
      propeptide cleavage. Our results indicate that high-affinity factor VIII binding
      sites are located on N-terminal disulfide-linked vWF subunits from which the
      propeptide has been cleaved.

PMID- 9657754
TI  - Ig receptor binding protein 1 (alpha4) is associated with a rapamycin-sensitive
      signal transduction in lymphocytes through direct binding to the catalytic
      subunit of protein phosphatase 2A.
AB  - Rapamycin is an immunosuppressant that effectively controls various immune
      responses; however, its action in the signal transduction of lymphocytes has
      remained largely unknown. We show here that a phosphoprotein encoded by mouse
      alpha4 (malpha4) gene transmitting a signal through B-cell antigen receptor (BCR)
      is associated with the catalytic subunit of protein phosphatase 2A (PP2Ac). The
      middle region of alph4, consisting of 109 amino acids (94-202), associates
      directly with PP2Ac, irrespective of any other accessory molecule. Rapamycin
      treatment disrupts the association of PP2Ac/alpha4 in parallel with the
      inhibitory effect of lymphoid cell proliferation. The effect of rapamycin was
      inhibited with an excess amount of FK506 that potentially completes the binding
      to FKBP. Rapamycin treatment also suppresses the phosphatase activity of cells
      measured by in vitro phosphatase assay. Introduction of the malpha4 cDNA into
      Jurkat cells or the increased association of PP2Ac/alpha4 by the culture with low
      serum concentration confers cells with rapamycin resistance. Moreover,
      glutathione S-transferase (GST)-alpha4 augments the PP2A activity upon myelin
      basic protein (MBP) and histone in the in vitro assay. These results suggest that
      alpha4 acts as a positive regulator of PP2A and as a new target of rapamycin in
      the activation of lymphocytes.

PMID- 9657755
TI  - Role for tyrosine phosphorylation and Lyn tyrosine kinase in fas receptor
      mediated apoptosis in eosinophils.
AB  - Fas ligand/Fas receptor molecular interactions have been implicated as having an
      important function for the regulation of eosinophil apoptosis. The purpose of the
      present study was to investigate biochemical events triggered by the engagement
      of the Fas receptor in freshly isolated human and mouse eosinophils. Activation
      of the Fas receptor on eosinophils with the agonistic anti-Fas monoclonal
      antibody (MoAb) resulted in increased tyrosine phosphorylation of several
      intracellular proteins. The tyrosine kinase inhibitors lavendustin A and
      genistein inhibited Fas receptor-induced cell death in both human and mouse
      eosinophils in vitro and prevented, at least partially, Fas receptor-mediated
      resolution of eosinophilic inflammation in a mouse in vivo model of lung
      eosinophilia. In addition, in freshly purified human eosinophils, lavendustin A
      prevented anti-Fas MoAb-induced proteolytic cleavage of lamin B, suggesting that
      tyrosine kinases may amplify the proteolytic signaling cascade within interleukin
      1beta converting enzyme (ICE) family proteases. Moreover, the tyrosine kinase Lyn
      was identified as being involved in Fas receptor-mediated cell death.
      Collectively, these results demonstrate that tyrosine phosphorylation is an
      important step in the generation of the Fas receptor-linked transmembrane death
      signal in eosinophils and that Lyn participates in this pathway.

PMID- 9657756
TI  - Shiga toxin type 1 activates tumor necrosis factor-alpha gene transcription and
      nuclear translocation of the transcriptional activators nuclear factor-kappaB and
      activator protein-1.
AB  - Shiga toxins (Stxs) produced by Shigella dysenteriae 1 and Escherichia coli have
      been implicated in the pathogenesis of bloody diarrhea, acute renal failure, and
      neurologic abnormalities. The pathologic hallmark of Stx-mediated tissue damage
      is the development of vascular lesions in which endothelial cells are swollen and
      detached from underlying basement membranes. However, in vitro studies using
      human vascular endothelial cells demonstrated minimal Stx-induced cytopathic
      effects, unless the target cells were also incubated with the proinflammatory
      cytokines tumor necrosis factor-alpha (TNF-alpha) or interleukin-1beta (IL-1bta).
      These cytokines have been shown to upregulate the expression of the Stx-binding
      membrane glycolipid globotriaosylceramide (Gb3). We show here that purified Stx1
      induces TNF secretion by a human monocytic cell line, THP-1, in a dose- and time
      dependent manner. Treatment of cells with both lipopolysaccharides (LPS) and Stx1
      results in augmented TNF production. Treatment with the nontoxic Gb3-binding
      subunit of Stx1 or with an anti-Gb3 monoclonal antibody did not trigger TNF
      production. Northern blot analyses show that Stx1 causes increased TNF-alpha
      production through transcriptional activation. Increased levels of TNF-alpha mRNA
      are preceded by the nuclear translocation of the transcriptional activators NF
      kappaB and AP-1 and the loss of cytoplasmic IkappaB-alpha. These data are the
      first to show that, in addition to direct cytotoxicity, Stxs possess cellular
      signaling capabilities sufficient to induce the synthesis of cytokines that may
      be necessary for target cell sensitization and the development of vascular
      lesions.

PMID- 9657757
TI  - Telomerase activity in Hodgkin's disease.
AB  - Telomere maintenance executed by the action of telomerase seems to be a
      prerequisite for immortalization. Telomerase is found in most cell lines and
      malignant tumors. A telomerase-independent mechanism for telomere maintenance in
      Hodgkin's disease has been proposed in the absence of detectable telomerase
      activity. In this study, telomerase activity was detected in 31 of 77 Hodgkin's
      disease samples and a strong correlation between eosinophilia and absence of
      detectable telomerase activity was found. Purified eosinophils and specifically
      eosinophil-derived neurotoxin and eosinophilic cationic protein, both
      ribonucleases, were found to degrade telomerase. Purified neutrophils also
      exhibited weak telomerase degradative activity. Reanalysis of previously
      telomerase-negative Hodgkin's disease samples with eosinophilia using
      ribonuclease inhibitors resulted in the detection of telomerase activity.
      Ribonuclease-containing cells in vivo thus have a considerable impact on the
      detectability of telomerase. In Hodgkin's disease samples without eosinophilia,
      24 of 27 exhibited telomerase activity at decreased levels compared with non
      Hodgkin's lymphomas and at increased levels compared with reactive nodes
      indicative of a telomerase positive tumor component in Hodgkin's disease.
      Telomerase positivity of the Hodgkin's and Reed-Sternberg cells in vivo was also
      supported by high levels of telomerase expression in Hodgkin's disease cell
      lines. Based on our data, Hodgkin's lymphomas are potential targets for
      antitelomerase therapy.

PMID- 9657758
TI  - Multiplex reverse transcription-polymerase chain reaction for simultaneous
      screening of 29 translocations and chromosomal aberrations in acute leukemia.
AB  - We have developed a multiplex reverse transcription-polymerase chain reaction (RT
      PCR) reaction, which enables us to detect 29 translocations/chromosomal
      aberrations in patients with acute lymphoid leukemia (ALL) and acute myeloid
      leukemia (AML). Through the construction and optimization of specific primers for
      each translocation, we have been able to reduce the set-up to 8 parallel
      multiplex PCR reactions, thus greatly decreasing the amount of work and reagents.
      We show the value of our set-up in a retrospective analysis on cryopreserved
      material from 102 AML and 62 ALL patients. The multiplex RT-PCR detected a hybrid
      mRNA resulting from a structural chromosomal aberration in 45 of 102 (44%) of the
      AML and in 28 of 62 (45%) of the pediatric ALL cases. Importantly, in 33% of AML
      and in 47% of the ALL cases with cytogenetic data, submicroscopic chromosomal
      aberrations or masked translocations were shown that were not detected in the
      cytogenetic analysis either for structural reasons or because of an insufficient
      number of metaphases obtained. This multiplex RT-PCR system, which can handle up
      to 10 patients with a response time of 2 working days, is thus an important tool
      that complements cytogenetic analysis in the up-front screening of acute leukemia
      patients and should provide a rapid and efficient characterization of leukemia
      cells, even in situations with sparse patient material.

PMID- 9657759
TI  - Malignant progenitors from patients with acute myelogenous leukemia are sensitive
      to a diphtheria toxin-granulocyte-macrophage colony-stimulating factor fusion
      protein.
AB  - We have previously demonstrated that human granulocyte-macrophage colony
      stimulating factor (GM-CSF) fused to a truncated diphtheria toxin (DT388-GMCSF)
      kills acute myelogenous leukemia (AML) cell lines bearing the GM-CSF receptor. We
      now report that exposure of malignant cells from 50 different patients with AML
      for 48 hours in culture to DT388-GMCSF reduces by a median of 1.6 logs (range, 0
      to 3.7 logs) the number of leukemic cells capable of forming colonies in
      semisolid media (leukemic colony-forming cells [CFU-L]) with a median IC50 of 3 x
      10(-12) mol/L (range, 5 to >4,000 x 10(-12) mol/L). Furthermore, the cell kill is
      dependent on the presence of high-affinity GM-CSF receptors on leukemic blasts,
      because CFU-L from 27 of 28 AML samples expressing > or = 35 GM-CSF receptors per
      cell were inhibited by the toxin, whereas the colony growth from all 4 leukemic
      samples (2 AML, 1 acute lymphoblastic leukemia [ALL], and 1 prolymphocytic
      leukemia [PLL]) that had less than 35 receptors per cell was unaffected by the
      drug. Sensitivity of CFU-L to DT388-GMCSF was seen regardless of the clinical
      responsiveness of the patient's leukemia to standard chemotherapy agents. In
      contrast, clonogenic cells from normal bone marrow formed colonies at near
      control numbers after exposure to much higher toxin concentrations (4 x 10(-9)
      mol/L) than those required to kill CFU-L from most patients. Thus, leukemic
      progenitors isolated directly from the peripheral blood of most AML patients show
      the same sensitivity to DT388-GMCSF as previously demonstrated for AML cell
      lines. Under the same conditions of exposure, normal hematopoietic progenitors
      are relatively unaffected by DT388-GMCSF, suggesting its potential as a
      therapeutic agent in AML.

PMID- 9657760
TI  - The reliability and specificity of c-kit for the diagnosis of acute myeloid
      leukemias and undifferentiated leukemias. The European Group for the
      Immunological Classification of Leukemias (EGIL).
AB  - We document findings on c-kit (CD117) expression in 1,937 pediatric and adult de
      novo acute leukemia cases, diagnosed in five single European centers. All cases
      were well characterized as to the morphologic, cytochemical, and immunologic
      features, according to the European Group for the Immunological Classification of
      Leukemias (EGIL). The cases included 1,103 acute myeloid leukemia (AML), 819
      acute lymphoblastic leukemia (ALL), 11 biphenotypic acute leukemia (BAL), and 4
      undifferentiated (AUL). c-kit was expressed in 741 (67%) AML cases, regardless of
      the French-American-British (FAB) subtype, one third of BAL, all four AUL, but
      only in 34 (4%) of ALL cases. The minority of c-kit+ ALL cases were classified
      as: T-cell lineage (two thirds), mainly pro-T-ALL or T-I, and B lineage (one
      third); cells from 62% of these ALL cases coexpressed other myeloid markers
      (CD13, CD33, or both). There were no differences in the frequency of c-kit+ AML
      or ALL cases according to age being similar in the adult and pediatric groups.
      Our findings demonstrate that c-kit is a reliable and specific marker to detect
      leukemia cells committed to the myeloid lineage, and therefore should be included
      in a routine basis for the diagnosis of acute leukemias to demonstrate myeloid
      commitment of the blasts. c-kit expression should score higher, at least one
      point, in the system currently applied to the diagnosis of BAL, as its myeloid
      specificity is greater than CD13 and CD33. Findings in ALL and AUL suggest that c
      kit identifies a subgroup of cases, which may correspond to leukemias either
      arising from early prothymocytes and/or early hematopoietic cells, both able to
      differentiate to the lymphoid and myeloid pathways.

PMID- 9657761
TI  - Epstein-Barr virus in nasal lymphomas contains multiple ongoing mutations in the
      EBNA-1 gene.
AB  - We have described 5 major subtypes of Epstein-Barr virus (EBV) based on
      variations in EBNA-1 sequences. These include P-ala (identical to the prototype
      B95.8 virus), P-thr, V-pro, V-leu, and V-val. Normal individuals often carry
      multiple EBV subtypes, the most common being P-ala, whereas EBV-associated tumors
      examined to date always contain a single subtype, which only on rare occasion is
      P-ala. The primary hypotheses that these observations generate are as follows:
      (1) Each of these EBV subtypes are naturally occurring, and in normal individuals
      the multiplicity of subtypes results from multiple infections. (2) EBV subtypes
      in normal individuals are generated in vivo from a single infecting virus subtype
      by mutations in EBNA-1. The second hypothesis essentially excludes the
      possibilities that the nonrandom association of certain subtypes with lymphomas
      is secondary to the geographic distribution of EBV subtypes and, if proven
      correct, could provide strong support for a direct role of EBV in tumorigenesis.
      In this report, we provide evidence for the latter hypothesis. We show that the P
      ala EBV subtype present in most nasal lymphomas undergoes and accumulates
      multiple mutations consistent with the generation of variant species of EBNA-1 in
      vivo. This phenomenon is similar to the generation of quasispecies in RNA viruses
      and is the first description of in vivo generation of subtypes in DNA viruses. In
      RNA-based viruses, including human immunodeficiency virus and hepatitis C virus,
      the emergence of quasispecies is linked to replication infidelity and
      significantly influences disease processes through its effect on viral tropism,
      the emergence of viruses resistant to the host defenses or to therapy, and
      pathogenicity. The present data thus raise important questions relating to the
      mechanisms whereby these mutations are generated in EBV and their relevance to
      the pathogenicity of EBV-associated lymphomas.

PMID- 9657762
TI  - Impaired granulocytic differentiation in vitro in hematopoietic cells lacking
      retinoic acid receptors alpha1 and gamma.
AB  - Transcripts for the retinoic acid receptors (RARs) alpha1, alpha2, gamma1, and
      gamma2 were found in the granulocytic lineage (Gr-1+ cells) through
      semiquantitative polymerase chain reaction (PCR) analysis. The screening of
      single cell cDNA libraries derived from hematopoietic progenitors also showed the
      presence of RARalpha and, to a lesser extent, RARgamma transcripts in committed
      granulocyte (colony-forming unit-granulocyte [CFU-G]) or granulocyte-macrophage
      (CFU-GM) colony-forming cells. The contribution of RARalpha1 and gamma to
      hematopoietic cell differentiation was therefore investigated in mice bearing
      targeted disruption of either one or both of these loci. Because RARgamma and
      RARalpha1gamma compound null mutants die shortly after birth, bone marrow cells
      were collected from fetuses at 18.5 days postcoitum (dpc) and evaluated for
      growth and differentiation in culture in the presence of Steel factor (SF),
      interleukin-3 (IL-3), and erythropoietin (Epo). The frequency of colony-forming
      cells from bone marrow populations derived from RARalpha1/gamma double null mice
      was not significantly different from that of RARgamma or RARalpha1 single nulls
      or from wild-type controls. In addition, the distribution of erythroid,
      granulocyte, and macrophage colonies was comparable between hematopoietic cells
      from all groups, suggesting that lineage commitment was not affected by the lack
      of RARalpha1 and/or RARgamma. Colony cells were then harvested individually and
      evaluated by morphologic criteria. While terminal granulocyte differentiation was
      evident in wild-type cells and colonies from either single null mutant, colonies
      derived from RARalpha1-/-gamma-/- bone marrow populations were blocked at the
      myelocyte and, to a lesser extent, at the metamyelocyte stages, whereas erythroid
      and macrophage differentiation was not affected. Together, these results indicate
      that both RARalpha1 and gamma are required for terminal maturation in the
      granulocytic lineage in vitro, but appear to be dispensable for the early stages
      of hematopoietic cell development. Our results raise the possibility that in
      acute promyelocytic leukemia (APL), the RARalpha fusion proteins cause
      differentiation arrest at a stage when further maturation requires not only
      RARalpha, but also RARgamma. Finally, bone marrow cells appear to differentiate
      normally in vivo, suggesting an effective compensation mechanism in the
      RARalpha1/gamma double null mice.

PMID- 9657763
TI  - Lack of clinically significant contact system activation during platelet
      concentrate filtration by leukocyte removal filters.
AB  - When blood (plasma) contacts certain foreign surfaces, factor XII can activate
      and trigger a series of reactions leading to cleavage of kininogens with
      subsequent release of bradykinin. In this study, we investigated two different
      widely used leukocyte removal filters, Pall PXL8K (A) and Asahi PLS-5A (B), to
      test whether clinically significant contact activation occurred during
      leukodepletion of platelet-rich plasma (PRP). Kininogens were measured by
      particle concentration fluorescence immunoassay (PCFIA), which can detect
      cleavage of high and low molecular weight kininogens (HK and LK), the parent
      molecules of bradykinin, to determine if contact activation had occurred. A
      slight, nonsignificant decrease in HK and LK was observed with filter A after the
      first 5 mL was filtered that returned to prefiltration levels by the end of the
      filtration. Specific TotK (the combined measurement of HK and LK heavy chains
      divided by plasma protein concentration) showed a small, significant decrease
      with filter A after the first 5 mL of platelet concentrates was filtered that
      returned to prefiltration levels by the end of the filtration. There were no
      significant increases or decreases in the cleaved kininogen index (CKI), an index
      of HK proteolytic activation or HK and LK destruction (with release of
      bradykinin). These data suggest that small amounts of both HK and LK initially
      adsorb to filter A and then desorb, primarily intact. These data also indicate
      that no significant contact activation, as measured by PCFIA, occurs during
      leukodepletion of platelet concentrates with either filter A or B.

PMID- 9657764
TI  - Regulation and processing of a precursor form of eosinophil granule major basic
      protein (ProMBP) in differentiating eosinophils.
AB  - The cDNA for eosinophil granule major basic protein (MBP) encodes a
      prepromolecule with a total length of 222 amino acids (preproMBP). PreproMBP
      includes a secretory leader of 15 amino acids, an acidic propiece of 90 amino
      acids, and a basic MBP portion of 117 amino acids. The function of the propiece,
      which has a predicted pI of 3.9, is unknown, but it gives proMBP an overall
      acidic charge. Because proMBP is not found in mature eosinophils, we analyzed
      eosinophil differentiation in interleukin-5 (IL-5)-stimulated umbilical cord stem
      cells cultured for 24 days. By immunofluorescence, proMBP appeared by day 6 and
      peaked on day 18, whereas MBP was prominent at days 12 to 24. By day 6, Western
      blots detected heterogeneous glycosylated 33-kD proMBP; its peak expression
      occurred on day 12. Western blots showed sequential processing of 33-kD proMBP to
      an 18-kD intermediate form and finally to 14-kD MBP. By dual label immunoelectron
      microscopy, proMBP was localized primarily to large uncondensed eosinophil
      granules, whereas MBP was localized to granules containing a condensed central
      area. Thus, proMBP is likely expressed and processed as the granule condenses in
      a multistep process to 14-kD MBP in differentiating eosinophils.

PMID- 9657765
TI  - The iron chelator L1 potentiates oxidative DNA damage in iron-loaded liver cells.
AB  - Iron-mediated carcinogenesis is thought to occur through the generation of oxygen
      radicals. Iron chelators are used in attempts to prevent the long term
      consequences of iron overload. In particular, 1,2-dimethyl-3-hydroxypyrid-4-one
      (L1), has shown promise as an effective chelator. Using an established
      hepatocellular model of iron overload, we studied the generation of iron
      catalyzed oxidative DNA damage and the influence of iron chelators, including L1,
      on such damage. Iron loading of HepG2 cells was found to greatly exacerbate
      hydrogen peroxide-mediated DNA damage. Desferrithiocin was protective against
      iron/hydrogen peroxide-induced DNA damage; deferoxamine had no effect. In
      contrast, L1 exposure markedly potentiated hydrogen peroxide-mediated oxidative
      DNA damage in iron-loaded liver cells. However, when exposure to L1 was
      maintained during incubation with hydrogen peroxide, L1 exerted a protective
      effect. We interpret this as indicating that L1's potential toxicity is highly
      dependent on the L1:iron ratio. In vitro studies examining iron-mediated
      ascorbate oxidation in the presence of L1 showed that an L1:iron ratio must be at
      least 3 to 1 for L1 to inhibit the generation of free radicals; at lower
      concentrations of L1 increased oxygen radical generation occurs. In the clinical
      setting, such potentiation of iron-catalyzed oxidative DNA damage at low L1:iron
      ratios may lead to long-term toxicities that might preclude administration of L1
      as an iron chelator. Whether this implication in fact extends to the in vivo
      situation will have to be verified in animal studies.

PMID- 9657766
TI  - Molecular defects of the RHCE gene in Rh-deficient individuals of the amorph
      type.
AB  - The deficiency of Rh proteins on the red blood cells from individuals of the
      Rhnull amorph type may be the result of homozygosity for a silent allele at the
      RH locus. This phenotype is also associated with the lack or reduced expression
      of glycoproteins (Rh50, CD47, LW, and glycophorin B), which interact with Rh
      polypeptides to form the multisubunit Rh membrane complex. In this study, we
      describe two molecular alterations affecting the RHCE gene in two unrelated
      Rhnull amorph individuals bearing Rh50 and CD47 normal transcripts. The first
      type of mutation, located at the donor splice-site in intron 4, induced the
      activation of two cryptic splice-sites within this intron and one such site in
      exon 4 that all generated aberrant transcripts. The second type of mutation
      affected the coding region and introduced a frameshift and a premature stop codon
      resulting in a shorter predicted protein (398 v 417 residues), including a
      completely different C-terminus of 76 amino acids. This suggests that protein
      folding and/or protein-protein interaction mediated by the C-terminal domain of
      the Rh proteins may play a role in the routing and/or stability of the Rh
      membrane complex.

PMID- 9657767
TI  - Six previously undescribed pyruvate kinase mutations causing enzyme deficiency.
AB  - Erythrocyte pyruvate kinase deficiency is the most common cause of hereditary
      nonspherocytic hemolytic anemia. We present 6 previously undescribed mutations of
      the PKLR gene associated with enzyme deficiency located at cDNA nt 476 G-->T
      (159Gly-->Val), 884 C-->T (295Ala-->Val), 943 G-->A (315Glu-->Lys), 1022 G-->A
      (341Gly-->Asp), 1511 G-->T (504Arg-->Leu), and 1528 C-->T (510Arg-->Ter). Two of
      these mutations are near the substrate binding site: the 315Glu-->Lys (943A)
      mutation may be involved in Mg2+ binding and 159Gly-->Val (476T) mutation has a
      possible effect on ADP binding. Four of six mutations produce deduced changes in
      the shape of the molecule. Two of these mutations, 504Arg-->Leu (1511T) and
      510Arg-->Ter (1528T), are located at the interface of domains A and C. One of
      them (510Arg-->Ter) is a deletion of the C-terminal residues affecting the
      integrity of the protein. The 504Arg-->Leu mutation eliminates a stabilizing
      interaction between domains A and C. Changes in amino acid 341(nt 1022) from Gly
      to Asp cause local perturbations. The mutation 295Ala-->Val (884T) might affect
      the way pyruvate kinase interacts with other molecules. We review previously
      described mutations and conclude that there is not yet sufficient data to allow
      us to draw conclusions regarding genotype/phenotype relationship.

PMID- 9657768
TI  - Full activity from human beta-globin locus control region transgenes requires
      5'HS1, distal beta-globin promoter, and 3' beta-globin sequences.
AB  - The locus control region (LCR) activates high-level human beta-globin transgene
      expression. LCR cassettes composed of 5'HS2-4 linked to the 815 bp beta-globin
      proximal promoter do not express fully. Here, we show that LCR (5'HS2-4) beta
      globin transgenes that also contain either 5'HS1 or the distal promoter fail to
      express fully in single- and low-copy transgenic mice. In contrast, full
      expression is obtained in the presence of both 5'HS1 and the distal promoter.
      Nine factor binding sites were identified in 5'HS1, using in vitro DNaseI
      footprint and gel retardation assays, and these include a strong Sp1/Sp3 site,
      four GATA-1 sites, and two sites that encompass an ACTAAC motif. LCR (5'HS1-4)
      beta-globin transgene constructs with the distal promoter deleted or replaced by
      spacer DNA show that specific distal promoter sequences are required for full
      expression. An LCR (5'HS1-4) transgene construct with truncated downstream beta
      globin gene sequences indicates that 3' sequences also play an important role.
      These results show that full expression of the beta-globin gene directed by the
      LCR requires 5'HS1, the distal beta-globin promoter, and 3' sequences, and has
      implications for gene therapy construct design and models of LCR activation.

PMID- 9657769
TI  - Rhnull disease: the amorph type results from a novel double mutation in RhCe gene
      on D-negative background.
AB  - Rhnull disease, which includes the amorph and regulator types, is a rare genetic
      disorder characterized by stomatocytosis and chronic hemolytic anemia. We studied
      here a German family transmitting a putative amorph Rhnull disease gene and
      identified a rare mutation causing the loss-of-function phenotype. We analyzed
      the genomic and transcript structure of RH30, RH50, and CD47, the three loci
      thought to be most critical for expression of the Rh complex in the red blood
      cell membrane. We showed that in this family the Rh50 and CD47 transcripts were
      normal in primary sequence. However, the RH30 locus contained an unusual double
      mutation in exon 7 of the RhCe gene, in addition to a deletion of the RhD gene.
      The mutation targeted two adjacent codons in multiple arrangements probably via
      the mechanism of microgene conversion. One scheme entails a noncontiguous
      deletion of two nucleotides, [ATT(Ile322)-->AT] and [CAC(His323)-->CC], whereas
      the other involves a T-->C transition [ATT(Ile322)--> ATC] and a dinucleotide
      deletion [CAC(His323)-->C]. They caused the same shift in open reading frame
      predicted to encode a shortened protein with 398 amino acids. The loss of two
      transmembrane domains and gain of a new C-terminal sequence are likely to alter
      the protein conformation and impair the Rh complex assembly. Our findings
      establish the molecular identity of an amorph Rhnull disease gene, showing that
      Rh30 and Rh50 are both essential for the functioning of the Rh structures as a
      multisubunit complex in the plasma membrane.

PMID- 9657770
TI  - Cytosine deaminase adenoviral vector and 5-fluorocytosine selectively reduce
      breast cancer cells 1 million-fold when they contaminate hematopoietic cells: a
      potential purging method for autologous transplantation.
AB  - Ad.CMV-CD is a replication incompetent adenoviral vector carrying a
      cytomegalovirus (CMV)-driven transcription unit of the cytosine deaminase (CD)
      gene. The CD transcription unit in this vector catalyzes the deamination of the
      nontoxic pro-drug, 5-fluorocytosine (5-FC), thus converting it to the cytotoxic
      drug 5-fluorouracil (5-FU). This adenoviral vector prodrug activation system has
      been proposed for use in selectively sensitizing breast cancer cells, which may
      contaminate collections of autologous stem cells products from breast cancer
      patients, to the toxic effects of 5-FC, without damaging the reconstitutive
      capability of the normal hematopoietic cells. This system could conceivably kill
      even the nondividing breast cancer cells, because the levels of 5-FU generated by
      this system are 10 to 30 times that associated with systemic administration of 5
      FU. The incorporation of 5-FU into mRNA at these high levels is sufficient to
      disrupt mRNA processing and protein synthesis so that even nondividing cells die
      of protein starvation. To test if the CD adenoviral vector sensitizes breast
      cancer cells to 5-FC, we exposed primary explants of normal human mammary
      epithelial cells (HMECs) and the established breast cancer cell (BCC) lines MCF-7
      and MDA-MB-453 to the Ad.CMV-CD for 90 minutes. This produced a 100-fold
      sensitization of these epithelial cells to the effects of 48 hours of exposure to
      5-FC. We next tested the selectivity of this system for BCC. When peripheral
      blood mononuclear cells (PBMCs), collected from cancer patients during the
      recovery phase from conventional dose chemotherapy-induced myelosuppression, were
      exposed to the Ad.CMV-CD for 90 minutes in serum-free conditions, little or no
      detectable conversion of 5-FC into 5-FU was seen even after 48 hours of exposure
      to high doses of 5-FC. In contrast, 70% of 5-FC was converted into the cytotoxic
      agent 5-FU when MCF-7 breast cancer cells (BCCs) were exposed to the same Ad.CMV
      CD vector followed by 5-FC for 48 hours. All of the BCC lines tested were shown
      to be sensitive to infection by adenoviral vectors when exposed to a recombinant
      adenoviral vector containing the reporter gene betagalactosidase (Ad.CMV
      betagal). In contrast, less than 1% of the CD34-selected cells and their more
      immature subsets, such as the CD34+CD38- or CD34(+)CD33- subpopulations, were
      positive for infection by the Ad.CMV-betagal vector, as judged by fluorescence
      activated cell sorting (FACS) analysis, when exposed to the adenoviral vector
      under conditions that did not commit the early hematopoietic precursor cells to
      maturation. When artificial mixtures of hematopoietic cells and BCCs were exposed
      for 90 minutes to the Ad.CMV-CD vector and to 5-FC for 10 days or more, a greater
      than 1 million fold reduction in the number of BCCs, as measured by colony
      limiting dilution assays, was observed. To test if the conditions were damaging
      for the hematopoietic reconstituting cells, marrow cells collected from 5-FU
      treated male donor mice were incubated with the cytosine deaminase adenoviral
      vector and then exposed to 5-FC either for 4 days in vitro before transplantation
      or for 14 days immediately after transplantation in vivo. There was no
      significant decrease in the reconstituting capability of the male marrow cells,
      as measured by their persistence in female irradiated recipients for up to 6
      months after transplantation. These observations suggest that adenovirus-mediated
      gene transfer of the Escherichia coli cytosine deaminase gene followed by
      exposure to the nontoxic pro-drug 5-FC may be a potential strategy to selectively
      reduce the level of contaminating BCCs in collections of hematopoietic cells used
      for autografts in breast cancer patients.

PMID- 9657771
TI  - Detection of microchimerism after allogeneic blood transfusion using nested
      polymerase chain reaction amplification with sequence-specific primers (PCR-SSP):
      a cautionary tale.
AB  - In bone marrow transplantation, the detection of chimerism is an important
      adjunct to the repertoire of tests available for determining acceptance of the
      graft. In solid organ transplantation, there is currently intense interest in the
      role that chimerism plays in both short- and long-term host reactivity to the
      graft. Allogeneic blood transfusion has been associated with a subtle
      immunosuppressive effect in renal transplantation and chimerism is implicated as
      a possible mechanism for this effect. To assess the survival of allogeneic cells
      after blood transfusion or transplantation, we have developed a technique based
      on molecular typing for HLA class II alleles, which enables the detection of
      donor-derived cells in patients receiving blood transfusions. While developing
      this technology, we investigated why we and others observe false amplification.
      Sequencing of false products has shown that they arise from amplification of both
      pseudogenes and non-pseudogenes present in the DNA under test. Elucidation of
      this phenomenon allows the amplification of these false products to be predicted
      in any given combination and hence avoided by the judicious selection of primers.
      Validation has been achieved by following donor alleles after transfusion of
      blood containing defined numbers of leukocytes expressing selected mismatched
      antigens.

PMID- 9657772
TI  - Role of class-II major histocompatibility complex (MHC)-antigen-positive donor
      leukocytes in transfusion-induced alloimmunization to donor class-I MHC antigens.
AB  - It has been shown that peripheral-blood mononuclear leukocytes (MNL) are
      responsible for transfusion-induced alloimmunization to donor major
      histocompatability complex (MHC) antigens. However, it is not known which subset
      of MNL is responsible for this immune response. Because elimination of class-II
      MHC antigen-positive passenger leukocytes effectively prolongs the survival of
      allografts, it has been hypothesized that class-II positive MNL are responsible
      for immunizing transfusion recipients to donor MHC antigens. To test this
      hypothesis, two different approaches were used. First, we compared the
      alloantigenicity of BALB/c mice (H-2(d)) peripheral blood MNL before and after
      depletion of class-II positive cells. CBA mice (H-2(k)) were used as transfusion
      recipients. Antibody development to donor class-I H-2 antigens was determined by
      flow cytometry and enzyme-linked immunoassay. After four weekly transfusions of
      MNL depleted for class-II positive cells, only 25% of recipient mice developed
      antibodies to donor H-2(d) antigens. In contrast, all mice transfused with
      control MNL became immunized. Second, we studied the alloantigenicity of
      peripheral MNL from C57BL/6 mice (H-2(b)) with homozygous deficiency of class-II
      MHC molecules in H-2 disparate recipient mice. After transfusions with class-II
      MHC molecule-deficient MNL, 0% of BALB/c, 40% of C57BR, and 25% of CBA-recipient
      mice developed antibodies to donor H-2(b) antigen. All control recipient mice
      were immunized. The antibody activities of the controls were also higher than
      those in the treatment group who became immunized. Thus, our study shows that
      class-II MHC antigen-positive MNL play a significant role in transfusion-induced
      alloimmunization to donor class-I MHC antigens. The results also support the
      hypothesis that direct antigen presentation by donor class-II positive MNL to the
      immune system of transfusion recipients is critical for the initiation of humoral
      immune response to donor MHC antigens.

PMID- 9657773
TI  - Prognostic value of cytogenetics and multidrug resistance (MDR1) in elderly
      patients with acute myeloid leukemia.

PMID- 9657774
TI  - Biological features of acute myeloid leukemia in the elderly.

PMID- 9657775
TI  - A case of Wiskott-Aldrich syndrome with dual mutations in exon 10 of the WASP
      gene: an additional de novo one-base insertion, which restores frame shift due to
      an inherent one-base deletion, detected in the major population of the patient's
      peripheral blood lymphocytes.

PMID- 9657776
TI  - c-kit activating mutations and mast cell proliferation in human leukemia.

PMID- 9657777
TI  - The role of factor XII in contact system activation.

PMID- 9657778
TI  - The prothrombin G20210A mutation and factor V Leiden mutation in patients with
      cerebrovascular disease.

PMID- 9657779
TI  - Pulmonary embolism. Hospitals should develop their own strategies for diagnosis
      and management.

PMID- 9657780
TI  - Vitamin B-6: food or medicine? The rules--and the politics--are different.

PMID- 9657781
TI  - Improving the management of soft tissue sarcoma. Diagnosis and treatment should
      be given in specialist centres.

PMID- 9657782
TI  - Bournewood: an indefensible gap in mental health law. Capacity is set to become a
      major clinicolegal issue.

PMID- 9657783
TI  - Quality to the fore in health policy--at last. But the NHS mustn't encourage
      quality improvement with punitive approaches.

PMID- 9657784
TI  - Randomised controlled trial of laparoscopic versus open mesh repair for inguinal
      hernia: outcome and cost.
AB  - OBJECTIVE: To compare tension-free open mesh hernioplasty under local anaesthetic
      with transabdominal preperitoneal laparoscopic hernia repair under general
      anaesthetic. DESIGN: A randomised controlled trial of 403 patients with inguinal
      hernias. SETTING: Two acute general hospitals in London between May 1995 and
      December 1996. SUBJECTS: 400 patients with a diagnosis of groin hernia, 200 in
      each group. MAIN OUTCOME MEASURES: Time until discharge, postoperative pain, and
      complications; patients' perceived health (SF-36), duration of convalescence, and
      patients' satisfaction with surgery; and health service costs. RESULTS: More
      patients in the open group (96%) than in the laparoscopic group (89%) were
      discharged on the same day as the operation (chi2 = 6.7; 1 df; P=0.01). Although
      pain scores were lower in the open group while the effect of the local
      anaesthetic persisted (proportional odds ratio at 2 hours 3.5 (2.3 to 5.1)),
      scores after open repair were significantly higher for each day of the first week
      (0.5 (0.3 to 0.7) on day 7) and during the second week (0.7 (0.5 to 0.9)). At 1
      month there was a greater improvement (or less deterioration) in mean SF-36
      scores over baseline in the laparoscopic group compared with the open group on
      seven of eight dimensions, reaching significance on five. For every activity
      considered the median time until return to normal was significantly shorter for
      the laparoscopic group. Patients randomised to laparoscopic repair were more
      satisfied with surgery at 1 month and 3 months after surgery. The mean cost per
      patient of laparoscopic repair was 335 pounds (95% confidence interval 228 pounds
      to 441 pounds) more than the cost of open repair. CONCLUSION: This study confirms
      that laparoscopic hernia repair has considerable short term clinical advantages
      after discharge compared with open mesh hernioplasty, although it was more
      expensive.

PMID- 9657785
TI  - Demographic and epidemiological determinants of healthcare costs in Netherlands:
      cost of illness study.
AB  - OBJECTIVES: To determine the demands on healthcare resources caused by different
      types of illnesses and variation with age and sex. DESIGN: Information on
      healthcare use was obtained from all 22 healthcare sectors in the Netherlands.
      Most important sectors (hospitals, nursing homes, inpatient psychiatric care,
      institutions for mentally disabled people) have national registries. Total
      expenditures for each sector were subdivided into 21 age groups, sex, and 34
      diagnostic groups. SETTING: Netherlands, 1994. MAIN OUTCOME MEASURES: Proportion
      of healthcare budget spent on each category of disease and cost of health care
      per person at various ages. RESULTS: After the first year of life, costs per
      person for children were lowest. Costs rose slowly throughout adult life and
      increased exponentially from age 50 onwards till the oldest age group (> or =
      95). The top five areas of healthcare costs were mental retardation,
      musculoskeletal disease (predominantly joint disease and dorsopathy), dementia, a
      heterogeneous group of other mental disorders, and ill defined conditions.
      Stroke, all cancers combined, and coronary heart disease ranked 7, 8, and 10,
      respectively. CONCLUSIONS: The main determinants of healthcare use in the
      Netherlands are old age and disabling conditions, particularly mental disability.
      A large share of the healthcare budget is spent on long term nursing care, and
      this cost will inevitably increase further in an ageing population. Non-specific
      cost containment measures may endanger the quality of care for old and mentally
      disabled people.

PMID- 9657786
TI  - Poverty, unemployment, and common mental disorders: population based cohort
      study.
AB  - OBJECTIVE: To determine whether poverty and unemployment increase the likelihood
      of or delay recovery from common mental disorders, and whether these associations
      could be explained by subjective financial strain. DESIGN: Prospective cohort
      study. SETTING: England, Wales, and Scotland. SUBJECTS: 7726 adults aged 16-75
      living in private households. MAIN OUTCOME MEASURES: Common mental disorders were
      assessed using the general health questionnaire, a self assessed measure of
      psychiatric morbidity. RESULTS: Poverty and unemployment (odds ratio 1.86, 95%
      confidence interval 1.18 to 2.94) were associated with the maintenance but not
      onset of episodes of common mental disorders. Associations between poverty and
      employment and maintenance of common mental disorders, however, were much smaller
      than those of cross sectional studies. Financial strain at baseline was
      independently associated with both onset (1.57, 1.19 to 2.07) and maintenance
      (1.86, 1.36 to 2.53) even after adjusting for objective indices of standard of
      living. CONCLUSIONS: Poverty and unemployment increased the duration of episodes
      of common mental disorders but not the likelihood of their onset. Financial
      strain was a better predictor of future psychiatric morbidity than either of
      these more objective risk factors though the nature of this risk factor and its
      relation with poverty and unemployment remain unclear.

PMID- 9657787
TI  - Underreporting of suspected adverse drug reactions to newly marketed ("black
      triangle") drugs in general practice: observational study.

PMID- 9657789
TI  - Alternative definitions 

PMID- 9657790
TI  - Words that count 

PMID- 9657788
TI  - Neglect of growth and development in the clinical monitoring of children and
      teenagers with inflammatory bowel disease: review of case records.

PMID- 9657791
TI  - From collaboration to commissioning: developing relationships between primary
      health and social services.

PMID- 9657792
TI  - Primary care: core values developing primary care: gatekeeping, commissioning,
      and managed care.

PMID- 9657794
TI  - The new NHS: national health service Act 

PMID- 9657793
TI  - Sexually transmitted infections.

PMID- 9657795
TI  - Deliberate self harm in Sri Lanka: an overlooked tragedy in the developing world.

PMID- 9657796
TI  - Managing demand for secondary care services: the changing context.

PMID- 9657797
TI  - Getting research findings into practice. When to act on the evidence.

PMID- 9657799
TI  - Golden age of surgery 

PMID- 9657798
TI  - Today's dogma may be tomorrow's joke 

PMID- 9657800
TI  - Impact of surgery for stress incontinence on morbidity. Effects of confounding
      variables on outcomes of incontinence surgery must be considered.

PMID- 9657801
TI  - Risk factors for winter outbreak of acute diarrhoea in France. Winter outbreaks
      of diarrhoea occur in United Kingdom too.

PMID- 9657802
TI  - Physical dependence on zopiclone. Prescribing this drug to addicts may give rise
      to iatrogenic drug misuse.

PMID- 9657803
TI  - Doctors need to know more about advance directives.

PMID- 9657804
TI  - Rescue thrombolysis may work even though primary thrombolysis has failed.

PMID- 9657805
TI  - Quality of life assessments may help some patients.

PMID- 9657806
TI  - Integrated care pathways increase use of guidelines.

PMID- 9657807
TI  - Lumbar puncture should not be delayed in subarachnoid haemorrhage.

PMID- 9657808
TI  - Doctors must understand terminology used to describe psychological therapies.

PMID- 9657809
TI  - Improving management of diabetes in residential and nursing homes. "Home clinic"
      facilitates communication with carers.

PMID- 9657810
TI  - Discrimination against gay and lesbian doctors goes against GMC's guidance.

PMID- 9657811
TI  - Levonorgestrel intrauterine device can be left in place for five years.

PMID- 9657812
TI  - Trevor lloyd davies 

PMID- 9657813
TI  - Shadow health team calls for GP ballot 

PMID- 9657814
TI  - Catastrophic cat care 

PMID- 9657815
TI  - Plus ca change.. 

PMID- 9657816
TI  - Ceremonial haemoglobinuria 

PMID- 9657818
TI  - Most of healthcare budget is spent on care not cure 

PMID- 9657817
TI  - Recovery is quicker after laparoscopic hernia repairbut there is a cost 

PMID- 9657820
TI  - GPs tend to report only serious reactions to new drugs 

PMID- 9657819
TI  - Financial strain has a major impact on mental health 

PMID- 9657822
TI  - Collaboration between primary care and social services can be improved 

PMID- 9657821
TI  - Children with inflammatory bowel disease fail to have their growth or sexual
      development recorded 

PMID- 9657823
TI  - Prediction of partitioning properties for benzaldehydes by various molecular
      descriptors.

PMID- 9657824
TI  - Development of an analytical method for the determination of congener specific
      PCBs in selected polymeric packaging materials.

PMID- 9657825
TI  - Optimization of enzymatic chlorine removal from Kraft pulp.

PMID- 9657826
TI  - Changes in selected indicators of liver impairment after repeated administration
      of mono- and polybromobenzenes in mice.

PMID- 9657827
TI  - Cadmium chloride prevents the rise in rat brown adipose tissue mitochondrial
      respiration in response to acute cold stress.

PMID- 9657828
TI  - Growth responses of Indian mustard [Brassica juncea (L.) Czern.] and its
      phytoextraction of lead from a contaminated soil.

PMID- 9657829
TI  - Growth responses of radish plants to soil cadmium and lead contamination.

PMID- 9657830
TI  - Sex specific interactions between Cd and Zn in three beetle species (Insecta,
      Coleoptera).

PMID- 9657831
TI  - Geochemistry of mercury in sediments of a sub-tropical coastal lagoon, Sepetiba
      Bay, southeastern Brazil.

PMID- 9657832
TI  - Copper bioaccumulation and depuration by red swamp crayfish, Procambarus clarkii.

PMID- 9657833
TI  - Hydrocarbon contamination in the Canary Islands. II. Intertidal limpet Patella
      ulyssiponensis aspera.

PMID- 9657834
TI  - Hydrocarbon and organochlorine residue concentrations in sediments from Bay of
      Chetumal, Mexico.

PMID- 9657835
TI  - Effects of exposure to contaminated sediments on the parasite fauna of American
      plaice (Hippoglossoides platessoides).

PMID- 9657836
TI  - Effects on tropical fish of soil sediments from Kafue river, Zambia.

PMID- 9657837
TI  - Sensitivity of ten aquatic species to long-term crude oil exposure.

PMID- 9657838
TI  - Effect of pentachlorophenol pollution towards microalgae and microbial activities
      in soil from a former timber processing facility.

PMID- 9657839
TI  - Acute toxicity of ammonia to Ceriodaphnia dubia and a procedure to improve
      control survival.

PMID- 9657840
TI  - Acute and chronic effects of indium chloride (InCl3) on tilapia (Oreochromis
      mossambicus) larvae.

PMID- 9657841
TI  - Acute and chronic effects of antimony chloride (SbCl3) on tilapia (Oreochromis
      mossambicus) larvae.

PMID- 9657842
TI  - Effect of methyl parathion-treated prey (Brachionus calyciflorus) on the
      population growth of the predator Asplanchna sieboldi (Rotifera).

PMID- 9657843
TI  - Prions and the prion disorders.
AB  - One of us remembers sitting in a high school biology class in 1977 being taught
      about scrapie, a naturally occurring disorder of sheep. The teacher had no
      particular interest in agriculture, but was pointing out some peculiar
      characteristics of this disease as a biological curiosity on a wet Friday
      afternoon. The prion disorders captured the imagination of a range of biologists
      (including that teacher) well before the epidemic of bovine spongiform
      encephalopathy (BSE) and the appearance of a new variant of the human prion
      disease, Creutzfeldt Jakob disease (CJD), in the UK, because of their
      extraordinary biology and the unique properties of the infectious agent. We
      review the results of studies leading to a convergence of evidence that the
      causative infectious agent, the 'prion', is devoid of nucleic acid and is
      composed of an abnormal isoform of a host-encoded protein, the prion protein
      (PrP).

PMID- 9657844
TI  - Genetic dissection of testicular weight in the mouse with the BXD recombinant
      inbred strains.
AB  - Testicular weights were studied in the mouse BXD recombinant inbred (RI) strains.
      These strains were derived from DBA/2J and C57BL/6J progenitors that differ
      significantly in their testicular weights (0.224 g +/- 0.015 vs. 0.161 g +/-
      0.03, P < 0.0001). The heritability of testicular weights was calculated to be
      0.53, and the minimum number of responsible effective factors was estimated to be
      5.7. The total genome scanning of the BXD RI strains with over 1000 markers
      revealed a quantitative trait locus (QTL) on mouse Chromosome (Chr) 13 near the
      D13Mit3 marker (LOD score 6.9). This QTL region was designated Twq1 and
      associated with over 75% of genetic variability.

PMID- 9657845
TI  - Genetics of obesity in KK mouse and effects of A(y) allele on quantitative
      regulation.
AB  - KK mouse is known as a polygenic model for noninsulin-dependent diabetes mellitus
      with moderate obesity. To identify the quantitative trait loci (QTLs) responsible
      for the body weight in KK, linkage analysis with 97 microsatellite markers was
      carried out into 192 F2 progeny, comprising 93 mice with a/a genotype at agouti
      locus and 99 mice with A(y)/a genotype, of a cross between C57BL/6J female and KK
      A(y) (A(y) congenic) male, thereby the influence of A(y) allele on the
      quantitative regulation of body weight was also examined. In F2 a/a mice, we
      identified a QTL on Chromosome (Chr) 4, and two loci with suggestive linkage on
      Chrs 15 and 18. In F2 A(y)/a mice, a QTL was identified on Chr 6, and two loci
      with suggestive linkage were identified on Chrs 4 and 16. That the QTL on Chr 4
      was held in common between F2 a/a and F2 A(y)/a progenies implies that this locus
      may be a primary component regulating body weight in KK and KK-A(y). These
      results suggest that the body weight in KK is controlled by multiple genes, and
      the different combination of loci is involved in the presence of A(y) allele. The
      QTL on Chr 6 seemed to determine the body weight by controlling fat deposition,
      because the linkage was identified on body weight and adiposity, and is suggested
      to be a component involved in the metabolic pathway in obesity caused by the A(y)
      allele.

PMID- 9657846
TI  - High-resolution mapping and recombination interval analysis of mouse chromosome
      17.
AB  - Analysis of homologous recombination in eukaryotes has shown that some meiotic
      crossing-over occurs preferentially at specific genomic sites of limited physical
      distance called recombinational hotspots. In the mouse, recombinational hotspots
      have only been defined in the major histocompatibility complex (MHC) on
      chromosome (Chr) 17. In an attempt to examine whether hotspots are unique to the
      MHC or are present throughout the genome, high-resolution linkage maps of Chr 17
      based on five backcrosses involving different inbred strains have been generated.
      These maps separate many markers that were previously shown at the same map
      position and allow a detailed analysis of recombination patterns across Chr 17.
      Corresponding recombination intervals in these maps have been compared for the
      identification of intervals with very little or no recombination in certain
      genetic crosses and considerable recombination in other genetic crosses. This
      approach has been termed Recombination Interval Analysis. Possible haplotype
      dependent non-MHC hotspots, as well as previously identified MHC hotspots, have
      been detected by interval analysis.

PMID- 9657848
TI  - An integrated genetic linkage map of the laboratory rat.
AB  - The laboratory rat, Rattus novegicus, is a major model system for physiological
      and pathophysiological studies, and since 1966 more than 422,000 publications
      describe biological studies on the rat (NCBI/Medline). The rat is becoming an
      increasingly important genetic model for the study of specific diseases, as well
      as retaining its role as a major preclinical model system for pharmaceutical
      development. The initial genetic linkage map of the rat contained 432 genetic
      markers (Jacob et al. 1995) out of 1171 developed due to the relatively low
      polymorphism rate of the mapping cross used (SHR x BN) when compared to the
      interspecific crosses in the mouse. While the rat genome project continues to
      localize additional markers on the linkage map, and as of 11/97 more than 3,200
      loci have been mapped. Current map construction is using two different crosses
      (SHRSP x BN and FHH x ACI) rather than the initial mapping cross. Consequently
      there is a need to provide integration among the different maps. We set out to
      develop an integrated map, as well as increase the number of markers on the rat
      genetic map. The crosses available for this analysis included the original
      mapping cross SHR x BN reciprocal F2 intercross (448 markers), a GH x BN
      intercross (205 markers), a SS/Mcw x BN intercross (235 markers), and a FHH/Eur x
      ACI/Hsd intercross (276 markers), which is also one of the new mapping crosses.
      Forty-six animals from each cross were genotyped with markers polymorphic for
      that cross. The maps appear to cover the vast majority of the rat genome. The
      availability of these additional markers should facilitate more complete whole
      genome scans in a greater number of strains and provide additional markers in
      specific genomic regions of interest.

PMID- 9657847
TI  - An improved linkage map of rat chromosome 3 with three mapping panels.
AB  - Our purposes were to develop an improved linkage map for rat Chromosome 3 and to
      develop new markers polymorphic between Dahl salt-sensitive (S) and Dahl salt
      resistant (R) rats. The linkage mapping panel consisted of three F2 populations
      totaling 359 rats. Twenty-five new markers were developed and placed on the
      linkage map. About half of these markers (13) were polymorphic between S and R
      rats. The final map spans 124.7 centiMorgans (cM) and includes 64 markers. The
      average distance between adjacent markers is 1.9 cM, and the largest separation
      is 10.5 cM.

PMID- 9657849
TI  - Construction of a rat genetic map by using randomly amplified microsatellite
      polymorphism (RAMP) markers.
AB  - Many rat strains have been employed in the genetic study of quantitative traits
      such as blood pressure. In such genetic studies, it is essential to prepare rat
      genetic maps fine enough to identify the genes regulating quantitative traits.
      However, it is not an easy task to isolate a sufficient number of genetic markers
      polymorphic between a particular pair of rat strains. In this study, we applied
      the randomly amplified microsatellite polymorphism (RAMP) method, a simple method
      to identify co-dominant markers (Wu et al. Nucleic Acids Res 22, 3257, 1994), to
      isolate markers polymorphic between the stroke-prone spontaneously hypertensive
      rat and the Wistar-Kyoto rat, a genetically hypertensive strain and its
      normotensive control strain, which share a common genetic background. We
      successfully identified 111 RAMP markers distributed throughout the rat genome
      after screening 3046 sets of primers. We also showed that we could isolate
      ordinary simple-sequence-length-polymorphism markers by cloning RAMP markers. The
      RAMP method is a simple and efficient way to identify co-dominant genetic markers
      on mammalian genomes.

PMID- 9657850
TI  - Structural and functional analysis of the porcine secretory carrier membrane
      protein 1 gene (SCAMP1).
AB  - The secretory carrier membrane proteins (SCAMPs) are highly conserved integral
      vesicle membrane components of the post-Golgi secretory and endocytic pathways.
      We have isolated and characterized the porcine SCAMP1 cDNA and gene coding for a
      variant of the SCAMP family. The SCAMP1 cDNA has a length of 3827 bp including a
      133-bp 5' and 2701-bp 3' untranslated region. The mRNA has an open reading frame
      of 1014 nt coding for a protein of 338 amino acids with a calculated molecular
      mass of 37.9 kDa and a pI of 7.9. The porcine SCAMP1 is 97.04% identical with the
      human and rat paralogs, respectively. The SCAMP1 gene consists of nine exons with
      sizes ranging from 78 to 2842 bp and spans at least 70 kb of genomic DNA on
      porcine Chromosome (Chr) 2q21-q22. The promoter of the SCAMP1 gene is TATA-box
      less, and transcription starts at a G-nucleotide 133 nt upstream the start codon.

PMID- 9657851
TI  - A QTL with major effect on milk yield and composition maps to bovine chromosome
      14.
AB  - A whole genome scan was undertaken in a granddaughter design comprising 1158
      progeny-tested bulls in order to map QTL influencing milk yield and composition.
      In this paper we report the identification of a locus on the centromeric end of
      bovine Chromosome (Chr) 14, with major effect on fat and protein percentage as
      well as milk yield. The genuine nature of this QTL was verified using the grand2
      daughter design, that is, by tracing the segregating QTL alleles from
      heterozygous grandsires to their maternal grandsons and confirming the predicted
      QTL allele substitution effect.

PMID- 9657852
TI  - Comparative analysis of 82 expressed sequence tags from a cattle ovary cDNA
      library.
AB  - In total, 82 ESTs were generated from 51 unique clones randomly selected from a
      cattle ovary cDNA library. Among these clones, 22 (42.1%) had 5' and/or 3' ends
      that matched with known human or other mammalian coding sequences, 18 (35.3%)
      matched human or other ESTs, and 11 (21.6%) represented novel transcripts with no
      significant match to any sequence in the databases. The relatively high frequency
      of ESTs with no matches in GenBank or dbEST indicates that bovine ovary may be a
      source of novel candidate genes for loci affecting cattle reproduction traits.
      Primers were designed for 11 ESTs that had human orthologs in GenBank. These ESTs
      were mapped to 10 bovine autosomes by PCR screening of a somatic cell hybrid
      panel. Among these 11 ESTs, 4 corresponded to genes previously mapped in humans
      and had chromosome assignments on the bovine map that were consistent with
      available comparative mapping data. Although the human orthologs of the remaining
      7 mapped bovine ESTs have not been mapped, the human map location could be
      predicted on the basis of existing comparative mapping data. Because of the
      general utility of our approach for comparative genome analysis, we have termed
      it comparative mapping by annotation and sequence similarity (COMPASS). With the
      cost of large-scale EST sequencing becoming more affordable, and the rapid
      expansion of DNA databases, it is likely that COMPASS will be a preferred
      strategy for high throughput comparative mapping.

PMID- 9657853
TI  - A SINE species from hippopotamus and its distribution among animal species.
AB  - Thirty sequences of a short interspersed repetitive element (SINE) were isolated
      from genomic DNA of Hippopotamus amphibius (hippopotamus). RNA polymerase III
      split promoter sequence was observed in all of the 30 sequences; and poly(A)-like
      structure at 3'-end, as well as direct repeat flanking to the repetitive sequence
      in many of the 30 sequences. A comparison of the consensus sequence of the 30
      sequences with sequences in a DNA database (DDBJ/GENBANK/EMBL) revealed 93%
      homology to the consensus sequence of a whale SINE, CHR-2, and 73% homology to
      mouse glutamic acid tRNA. Phylogenetic analysis of tRNA-related regions of the
      sequences with all of the mouse tRNAs revealed that glutamic acid tRNA was
      genetically closest to the hippopotamus SINE. In addition, the tRNA-related
      region of the consensus sequence was folded into a cloverleaf structure as with
      mouse glutamic acid tRNA. These findings led us to conclude that the SINE of
      hippopotamus was genetically related to a whale SINE, CHR-2 [the hippopotamus
      SINE was named CHR-2(hippo)] and was a retroposon derived from glutamic acid
      tRNA. Hipo53 and hipo95, which were the genetically most separated CHR-2(hippo)
      sequences in the present study, were used as a probe for dot-blot hybridization
      to examine the distribution of their homologous sequences among animal species.
      Although the distribution spectra of hipo53 and hipo95 homologous sequences in
      animal species differed to some extent, large amounts of both sequences were
      found in Hippopotamus amphibius and Globicephala macrorhynchus (whale); and small
      amounts in most of the animal species in Artiodactyla examined. These findings
      indicated that the hippopotamus and whale had more recently branched off from the
      clade that includes chevrotain and pecorans than the other animal species in the
      clade. The 30 CHR-2(hippo) sequences were aligned, and the substitution rates
      among the sequences were calculated with a different substitution rate model for
      transition and for transversion. The calculation combined with the mutation rate
      of the pseudogenes (r = 4.6 x 10(9)) indicated that CHR-2(hippo) sequences
      diversified at least 132 million years ago (Myr).

PMID- 9657854
TI  - Chromosomal localization and characterization of the stannin (Snn) gene.
AB  - Stannin is a protein that has been localized to trimethyltin-sensitive cell
      populations, and evidence suggests it plays a role in the toxic effects of
      organotins. In this study, we have isolated a mouse stannin genomic clone and
      have characterized the gene's intron-exon organization, promoter region, and
      chromosomal location. We have also isolated a partial human stannin cDNA clone
      and analyzed the open reading frame. The mouse genomic clone spans approximately
      19 kb and consists of one intron and two exons. The splice site consensus
      sequence was maintained at all intron-exon junctions. Promoter analysis suggests
      that two putative promoter sites exist, each containing multiple regulatory
      elements and transcription factor-binding sites. Fluorescence in situ
      hybridization analysis localized stannin to mouse Chromosome (Chr) 16 at band A2.
      This region is homologous to the proximal region of human Chr 16 (16p13) to which
      stannin has been previously mapped. Sequence analysis revealed that the 264-bp
      open reading frame was identical between rat and mouse. The human sequence was
      98% identical, with two amino acid substitutions near the c-terminal end of the
      peptide. These data suggest that stannin is highly conserved between species, and
      its unusual pattern of cellular expression may, in part, be explained via cell
      specific promoters.

PMID- 9657855
TI  - Gene structure and map location of the murine homolog of the Huntington
      associated protein, Hap1.
AB  - Huntington's Disease (HD) is an inherited progressive neurodegenerative disorder
      associated with a mutation in a gene expressed in both affected and non-affected
      tissues. The selective neuropathology in HD is thought to be mediated in part
      through interactions with other proteins including the Huntington Associated
      Protein, HAP-1, which is predominantly expressed in the brain. We have mapped its
      murine homolog, Hap1, to mouse Chr 11 (band D), which shares extensive synteny
      with human Chr 17 including the region 17q21-q22, where the gene for
      'frontotemporal dementia and parkinsonism linked to chromosome 17' has bee
      mapped. In addition, we have sequenced a 21,984 base pair (bp) genomic clone
      encompassing the entire Hap1 gene. It is organized as 11 exons and flanked by
      exons from potentially one or more novel genes. At least three Hap1 transcripts
      (Hap1-A; Hap1-B; Hap1-C) can be formed by alternative splicing at the 3' end of
      the gene leading to protein isoforms with novel C-termini.

PMID- 9657856
TI  - Genomic structure and chromosome location of the murine PDE1B phosphodiesterase
      gene.
AB  - Cyclic nucleotide phosphodiesterases (PDEs) catalyze the hydrolysis of cAMP and
      cGMP, thereby participating in regulation of the intracellular concentrations of
      these second messengers. The PDE1 family is defined by regulation of activity by
      calcium and calmodulin. We have cloned and characterized the mouse PDE1B gene,
      which encodes the 63-kDa calcium/calmodulin-dependent PDE (CaM-PDE), an isozyme
      that is expressed in the CNS in the olfactory tract, dentate gyrus, and striatum
      and may participate in learning, memory, and regulation of phosphorylation of
      DARPP-32 in dopaminergic neurons. We screened an I-129/SvJ mouse genomic library
      and identified exons 2-13 of the PDE1B gene that span 8.4 kb of genomic DNA.
      Exons range from 67 to 205 nucleotides and introns from 91 to 2250 nucleotides in
      length. Exon 1 was not present in the 3 kb of genomic DNA 5' to exon 2 in our
      clones. The mouse PDE1B gene shares many similar or identical exon boundaries as
      well as considerable sequence identity with the rat PDE4B and PDE4D genes and the
      Drosophila dunce cAMP-specific PDE gene dnc, suggesting that these genes all
      arose from a common ancestor. Using fluorescence in situ hybridization, we
      localized the PDE1B gene to the distal tip of mouse Chromosome (Chr) 15.

PMID- 9657857
TI  - Traced orthologous amplified sequence tags (TOASTs) and mammalian comparative
      maps.
AB  - Progress on mammalian comparative maps could be significantly accelerated by
      developing reagents defining orthologous landmarks in the genome of many
      mammalian species. Using the large databases of gene sequences, we designed 225
      orthologous gene-specific primer pairs corresponding to 146 functional genes. Of
      these 225 primer pairs, 155 (68.9%), 182 (80.9%), 126 (56.0%), and 82 (36.4%)
      produced a single PCR product when tested against human, pig, dog, and hamster
      genomic DNA, respectively. In addition to the general rules of primer designing,
      particular factors must be taken into consideration when choosing gene-specific
      universal primers--for instance, preference for single-exon regions or highly
      conserved segments among species, avoidance of GC-rich regions. Sequencing all
      the canine PCR products traced by these primers demonstrated that of 123 traced
      canine fragments with readable and reliable sequences, 121 (98.4%) were found to
      match the GenBank orthologous sequences used for designing the primers, after a
      BLAST search. Comparative characterization of PCR fragments among human, pig,
      dog, and hamster revealed that the length of a single exon was much conserved
      among species, with few exceptions. As the fragments were traced with
      amplification by orthologous gene-specific primers, we suggest they be termed
      Traced Orthologous Amplified Sequence Tags (TOASTs).

PMID- 9657858
TI  - The dominant mouse mutations fused toes (Ft) and oligosyndactylism (Os) are not
      allelic.

PMID- 9657859
TI  - Male sex determination in the spiny rat Tokudaia osimensis (Rodentia: Muridae) is
      not Sry dependent.

PMID- 9657860
TI  - Localization of the genes encoding the type I diabetes autoantigens, protein
      tyrosine phosphatases IA2 and IAR.

PMID- 9657861
TI  - Characterization of murine BCAT genes: Bcat1, a c-Myc target, and its homolog,
      Bcat2.

PMID- 9657862
TI  - Genetic mapping of the Na(+)-taurocholate cotransporting polypeptide to mouse
      chromosome 12.

PMID- 9657865
TI  - Volume 247, Number 1 (1997), in Article No. AB972008, "High-Performance Liquid
      Chromatographic Determination of Nitric Oxide Synthase-Related Arginine
      Derivatives in Vitro and in Vivo," by Jens Meyer, Nadja Richter, and Markus
      Hecker, pages 11-16:
AB  - Copyright

PMID- 9657863
TI  - Assignment of the growth hormone receptor gene to band q17 of the homeologous
      sheep 16 and cattle 20 chromosomes.

PMID- 9657866
TI  - Volume 255, Number 1 (1998), in Article No. AB972457, "Three-Minute G+A Specific
      Reaction for DNA Sequencing," by Song-Tao Liu and Guo-Fan Hong, pages 158-159:
AB  - Copyright

PMID- 9657867
TI  - Characterization of proteins utilized in the desulfurization of petroleum
      products by matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry.
AB  - Matrix-assisted laser desorption ionization time-of-flight mass spectrometry
      (MALDI/TOF/MS) with delayed extraction is utilized in linear, reflected-ion and
      post-source decay (PSD) modes to directly characterize enzymes being developed
      for use in a petroleum desulfurization process. The DNA sequence for the genes
      isolated from Rhodococcus sp. strain IGTS8 that produce three of the four enzymes
      under study had been previously reported with a discrepancy in residue
      assignments for one of the enzymes, dsz-C. The use of proteolytic digests
      followed by MALDI/TOF/MS with delayed extraction in the reflected-ion mode
      provided sequence-specific information with mass accuracies exceeding 40 ppm over
      a range of masses and signal-to-noise values. Peptide mapping of >80% of the
      residues was accomplished for all four proteins. The use of PSD established the
      true sequence for dsz-C, resolving the discrepancy in the literature. A
      posttranslational loss of N-terminal methionine was observed for each of the four
      proteins in linear MALDI/MS and was reconfirmed by peptide mapping for three of
      the proteins.

PMID- 9657868
TI  - A quantitative mannose 6-phosphate receptor-based in vitro assay for recombinant
      human N-acetylgalactosamine-4-sulfatase.
AB  - An assay was developed, using two similar formats, to simultaneously measure both
      the lysosomal targeting receptor binding and enzyme activity of the recombinant
      human enzyme N-acetylgalactosamine-4-sulfatase. This assay also has potential
      application for all phosphorylated lysosomal enzymes that contain mannose-6
      phosphate residues. The receptor was either purified from fetal bovine sera then
      adsorbed, or produced in situ by growing and fixing diploid human fibroblast-like
      cells, to a solid phase. The enzyme substrate was 4-methylumbelliferyl sulfate
      which fluoresces after cleavage of the sulfate moiety. Both the precursor and
      mature forms of the recombinant enzyme were used to demonstrate the specificity
      and usefulness of the assay. The assay is rapid and sensitive and has a wide
      dynamic range. Association between the receptor and the mannose-6-phosphate
      residues was abrogated in the presence of a competitive inhibitor, mannose 6
      phosphate. However, partial activity was still measured when the mature enzyme
      was incubated in the presence of mannose 6-phosphate when using the fixed
      fibroblast format. This would indicate that the recombinant enzymes contain at
      least one terminal sugar moiety other than mannose 6-phosphate which can
      recognize receptors on the surface of human fibroblast-like cells. Other possible
      applications of this assay are also discussed.

PMID- 9657869
TI  - Reconstituting ubiquitination reactions with affinity-purified components and 32P
      ubiquitin.
AB  - The discovery of protein ubiquitination in a broad range of organisms and
      experimental settings has raised the need for a straightforward way to
      characterize the mechanism of substrate targeting, using purified components. The
      mechanism of ubiquitin conjugation to proteins has been extensively studied and
      is mediated by a family of evolutionarily conserved proteins. We have used
      previously described expression systems to purify the relevant targeting
      components of the ubiquitin system. These methods yielded substantial amounts of
      highly purified and catalytically active enzymes that permitted their use in
      reconstituting protein ubiquitination. We monitored ubiquitination reactions with
      32P-ubiquitin rather than 125I-ubiquitin. This advance makes the procedure
      accessible to a broader range of experimentalists, since it eliminates the
      additional concerns involved in handling 125I-isotope. Furthermore, the
      strategies described here can be used to investigate the effects of specific
      mutations introduced into ubiquitin or the targeting components (E1, Ubc/E2, and
      E3) of this pathway.

PMID- 9657870
TI  - Detection of the hereditary hemochromatosis gene mutation by real-time
      fluorescence polymerase chain reaction and peptide nucleic acid clamping.
AB  - Hereditary hemochromatosis (HH), an iron overload disease, is the most common
      known inheritable disease. The most prevalent form of HH is believed to be the
      result of a single base-pair mutation. We describe a rapid homogeneous mutation
      analysis method that does not require post-polymerase chain reaction (PCR)
      manipulations. This method is a marriage of three emerging technologies: rapid
      cycling PCR thermal cyclers, peptide nucleic acid (PNA) probes, and a new double
      stranded DNA-selective fluorescent dye, Sybr Green I. The LightCycler is a rapid
      thermal cycler that fluorometrically monitors real-time formation of amplicon
      with Sybr Green I. PNAs are DNA mimics that are more sensitive to mismatches than
      DNA probes, and will not serve as primers for DNA polymerases. PNA probes were
      designed to compete with PCR primers hybridizing to the HH mutation site. Fully
      complemented PNA probes at an 18:1 ratio over DNA primers with a mismatch result
      in suppression of amplicon formation. Conversely, PNA probes with a mismatch will
      not impair the binding of a complementary primer, culminating in amplicon
      formation. A LightCycler-based rapid genetic assay has been developed to
      distinguish HH patients from HH carriers and normal individuals using PNA
      clamping technology.

PMID- 9657871
TI  - Adaptor ligation-based polymerase chain reaction-mediated walking.
AB  - An improved method of adaptor ligation PCR was developed for isolation of unknown
      sequences flanking a known DNA sequence. It was determined that the specificity
      of the adaptor ligation-based walking technique could be significantly enhanced
      by using uniquely blocked adaptors along with removal of unligated genomic DNA by
      exonuclease III digestion. This technique was utilized to isolate three novel
      promoter regions from three different Zea mays (maize) peroxidase genes.
      Sequences encoding a putative maize 6-phosphogluconate dehydrogenase gene were
      also isolated and confirmed by sequence analysis. The described improvements
      could be applied to other existing adaptor ligation-based PCR walking techniques.

PMID- 9657873
TI  - In vitro measurement of beta-lactamase-catalyzed ampicillin hydrolysis by
      recombinant Escherichia coli extracts using quantitative high-performance liquid
      chromatography.
AB  - We report a rapid and simple protocol for measuring the beta-lactamase activity
      from recombinant Escherichia coli cells transformed with any of the common
      plasmid vectors that provide ampicillin resistance through constitutive
      expression and periplasmic localization of the beta-lactamase TEM-1. The
      hydrolytic enzyme was extracted from the E. coli periplasm and the beta-lactamase
      activity determined by measuring conversion of ampicillin to aminobenzyl
      penicilloic acid using quantitative high-performance liquid chromatography. Under
      saturating conditions the in vitro assay was linear as a function of both
      incubation time and enzyme concentration. Application of this assay to
      investigate TEM-1 expression, from two different protein expression vector
      systems, demonstrated the potential importance of this assay in studies of
      recombinant protein expression and translocation.

PMID- 9657872
TI  - High-performance capillary electrophoretic characterization of different types of
      oligo- and polysialic acid chains.
AB  - We have carried out comparative structural analysis of novel oligo- and
      polysialic acid chains from diverse sources. Controlled acid hydrolysates of (a)
      colominic acid, alpha2-->8-linked homopolymer of N-acetylneuraminic acid
      (Neu5Ac), (b) alpha2-->8-linked oligo/polyNeu5Gc chains present in rainbow trout
      egg polysialoglycoprotein, and (c) alpha2-->8-linked oligomers of
      deaminoneuraminic acid (KDN) residues of KDN-rich glycoprotein derived from
      rainbow trout vitelline envelope were analyzed by high-performance capillary
      electrophoresis (HPCE). The results showed that three different types of alpha2-
      >8-linked oligosialic acids having same degree of polymerization can be separated
      by HPCE. A partial hydrolysate of colominic acid with mild acid was shown by CE
      to form intramolecular esters during the controlled hydrolysis and the subsequent
      workup procedure. In contrast, lactonization of (-->5-Oglycolyl-Neu5Gcalpha2-
      >)n, alpha2-->5-Oglycolyl-linked homopolymer of N-glycolylneuraminic acid
      (Neu5Gc) present in the egg jelly coat of sea urchin, did not take place as
      readily as in (-->8Neu5Acalpha2-->)n.

PMID- 9657874
TI  - Single-molecule analysis of restriction DNA fragments using fluorescence
      correlation spectroscopy.
AB  - The cleavage of fluorescence-labeled M13DNA (7250 bp) using HaeIII, HgaI, BsmAI,
      and BspMI was analyzed by fluorescence correlation spectroscopy (FCS) in a small
      volume (1.5 x 10(-15) liters). The digestion process can be monitored by the
      decrease in amplitude of the fluorescence correlation function while the original
      DNA molecule is divided into several fragments by the enzymes. To analyze this
      reaction by FCS, we derived a practical equation for estimating the number of
      molecules in the FCS measurements. Under standard enzymatic conditions, HaeIII
      and BsmAI digested fluorescence-labeled DNA to completion in the range of 8 h,
      whereas HgaI and BspMI digested the DNA after 40 h. The comparison of recognition
      sequences suggested that some tagged nucleotides could be inserted between the
      recognition site and the cleavage site of the slow enzyme group. The decrease in
      amplitude in the fluorescence correlation function quantitatively monitors the
      hydrolysis of DNA during the digestion process.

PMID- 9657875
TI  - Enzyme-complemented activatorsorbent assay (ECASA): genetic engineering for
      enzyme-linked immunosorbent assay-type mercuric ion detection.
AB  - The sensor component of bacterial mercury resistance systems is the
      metalloregulatory protein MerR, which has nanomolar sensitivity and high
      selectivity for Hg(II). A fusion protein of MerR and the alpha-peptide part of
      beta-galactosidase (LacZalpha) was constructed by fusing the relevant genes. The
      protein exhibited both MerR functions and alpha-complementing activity to the
      inactive LacZDeltaM15 (M15) protein. The bifunctional character of the
      appropriate MerR-LacZalpha-complemented M15 protein (MerR-LacZalpha:M15 protein
      complex) was used to develop a Hg(II)-specific enzyme-complemented
      activatorsorbent assay. Hg(II) was immobilized and presented on a matrix taking
      advantage of the high affinity of Hg(II) to SH residues. The immobilized Hg(II)
      could be specifically detected down to the parts-per-billion level by quantifying
      the beta-galactosidase activity of the bound fusion protein complex.

PMID- 9657876
TI  - High-yield deblocking of amino termini of recombinant immunoglobulins with
      pyroglutamate aminopeptidase.
AB  - For larger proteins, efficient deblocking prior to Edman sequencing is especially
      important to obtain quality, extended sequencing data which is limited by the
      stepwise accumulation of background from the random acid hydrolysis of the
      protein. Therefore, any portion that remains blocked contributes to the
      undesirable background. We report an optimized procedure for the removal of
      pyroglutamate (pGlu) by pyroglutamate aminopeptidase (PGAP) and demonstrate its
      use for the quantitative deblocking of several humanized recombinant antibodies
      (rIgGs). The rIgGs with blocked heavy chain provided an advantageous system in
      which removal of pGlu from the heavy chain was determined as a ratio of the
      deblocked heavy chain to the light chain in the first cycle of sequencing; i.e.,
      the light chain was used as an internal standard. The reaction temperature,
      reaction time, enzyme-to-substrate ratio, denaturation, and
      reduction/carboxymethylation prior to digestion, and different commercial enzymes
      were evaluated. The optimized procedure involves reduction/carboxymethylation in
      guanidine buffer, buffer exchange by gel-permeation chromatography, and overnight
      PGAP digestion at 37 degrees C. Five different rIgGs, including one with blocked
      heavy and light chains, were deblocked in nearly quantitative yields using this
      procedure.

PMID- 9657877
TI  - Nonradioactive phosphopeptide assay by matrix-assisted laser desorption
      ionization time-of-flight mass spectrometry: application to calcium/calmodulin
      dependent protein kinase II.
AB  - Matrix-assisted laser desorption ionization time-of-flight mass spectrometry
      (MALDI-TOF) was used to quantify the phosphopeptide produced by
      calcium/calmodulin-dependent protein kinase II (CaMK II). MALDI-TOF measurements
      were performed in a linear and positive ion mode with delayed extraction excited
      at various laser powers and at different sampling positions, i.e., different loci
      of laser illumination. We find that the ratio of the peak area of the substrate
      (S) to that of its monophosphorylated form (SP) for a given mixture is constant,
      independent of the laser powers and/or of the sample loci illuminated by the
      laser. We also find that the fraction of phosphorylation determined by MALDI-TOF,
      or fMALDI-TOF, is proportionally smaller than that determined by HPLC, or fHPLC;
      the ratio fMALDI-TOF/fHPLC was 0.797 +/- 0.0229 (99% confidence limit, n = 7) for
      a 30-mer peptide substrate used in this study. A low mass gate, which turns off
      the detector temporarily, improved the ratio fMALDI-TOF/fHPLC to 0.917 +/- 0.0184
      (99% confidence limit, n = 7). Our interpretation of this result is that the
      reduction of the phosphopeptide peak in the MALDI-TOF measurement is likely to be
      caused by a temporal loss of detector function rather than by a lower efficiency
      of ionization for the phosphopeptide compared with its parent species. In these
      measurements the experimental errors, up to the 50% phosphorylation state, were
      less than 5%. After an adjustment made based on the fMALDI-TOF/fHPLC ratio of
      0.917, MALDI-TOF gave an accurate measurement for the kinetics of the CaMK II
      phosphorylation reaction. Since only a small volume of the reaction mixture,
      typically containing 3 to 50 pmol of substrate, is required for the MALDI-TOF
      measurement, this method can be adapted to a nonradioactive microscale assay for
      CaMK II and also for other protein kinases.

PMID- 9657878
TI  - Ethanol biosensors and electrochemical oxidation of NADH.
AB  - Comparative studies of the electrochemical oxidation of reduced nicotinamide
      coenzyme (NADH) at the surfaces of chemically modified graphite paste electrodes
      (CMEs) are reported. Three different electroactive materials,
      tetracyanoquinodimethane (TCNQ), tetrathiafulvalene (TTF), and dimethyl ferrocene
      (dmFc), were used to construct three different chemically modified paste
      electrodes. The oxidation of NADH was examined on the basis of cyclic
      voltammetric measurements. The results show that all three mediators (TCNQ, TTF,
      and dmFc) behave as efficient mediators of the oxidation of NADH. The typical
      response curves of NADH at the CMEs surfaces are reported. Incorporating alcohol
      dehydrogenase and electroactive materials (TCNQ, TTF, and dmFc) within the
      graphite paste electrodes has led to the development of ethanol biosensors.
      Typical response curves for the ethanol analysis are reported. Comparative
      studies on the mediated electrochemical responses of the biosensors to ethanol
      are discussed.

PMID- 9657879
TI  - Distinguishing small molecular mass differences of proteins by mass spectrometry.
AB  - Electrospray ionization-Fourier transform ion cyclotron resonance (ESI-FTICR)
      mass spectrometry allows for high-resolution, accurate mass analysis of multiply
      charged ions of proteins. In the work described here, the ability of ESI-FTICR to
      distinguish small differences in molecular mass is evaluated. Ubiquitin was used
      as an internal mass calibration standard to measure the molecular mass of
      cytochrome c, myoglobin, and several carbonic anhydrase isoforms. Mass
      calibration was based on the tallest isotopic peak of each ubiquitin charge
      state. Ubiquitin performed well as an internal standard because its charge states
      covered the appropriate mass range, interference was minimal, and the tallest
      peak was easily identified. The peak masses of cytochrome c (12.5 kDa) and
      myoglobin (17 kDa) were measured to an accuracy of about 0.02 Da (<2ppm).
      However, errors of 1.0 Da were observed for some individual determinations
      because of the difficulty in identifying the tallest peak. When the technique was
      applied to bovine carbonic anhydrase II, even combining data from several charge
      states did not yield an unequivocal assignment of the tallest peak, resulting in
      a mass assignment of 29,023.7 or 29,024.7. Similarly, measurements of two
      isoforms with a mass difference of 1 Da, human carbonic anhydrase I, pI 6.0 and
      6.6, yielded overlapping values for the mass of the tallest peak. However, these
      two isoforms were clearly distinguished by (a) identification of the tallest peak
      using a measurement of average mass as a guide and (b) comparison of the isotopic
      peak intensity patterns.

PMID- 9657880
TI  - A binding shift assay for the zinc-bound and zinc-free HIV-1 nucleocapsid protein
      by capillary electrophoresis.
AB  - Affinity capillary electrophoresis was used to detect a shift in mobility when a
      zinc ion binds to the highly basic nucleocapsid protein (NCp7) of HIV-1. NCp7
      contains two Cys-X2- Cys-X4-His-X4-Cys zinc fingers. With constant concentrations
      of NCp7 as a receptor and various concentrations of zinc as a ligand in the
      sample buffer and the electrophoresis buffer, we observed changes in
      electrophoretic mobilities of NCp7 protein when complexes were formed with zinc.
      Scatchard analysis of the mobility indicates the presence of at least two types
      of binding sites for zinc. At pH 6.0, one site is shown to bind zinc strongly
      with a binding constant Kb = 3.25 x 10(5) M-1 and the second site has a Kb = 1.8
      x 10(5) M-1. The binding of zinc to the first zinc finger decreased the affinity
      of zinc for the second zinc finger approximately twofold. The Hill coefficient
      for this negative cooperativity is 0.9. A series of NCp7 mutants were also
      examined in the assay to determine their ability to bind zinc. This assay affords
      a quick method to observe a zinc ion binding to NCp7 and to calculate binding
      constants.

PMID- 9657881
TI  - Methodological aspects of measuring human skeletal muscle electrolyte content and
      ouabain binding capacity.
AB  - The aim of the study was to evaluate the use of freeze-dried and dissected small
      muscle biopsy specimens ("dry") for the determination of human muscle electrolyte
      content and ouabain binding capacity, compared with an easier method, without
      this freeze-drying step ("wet"). Freeze-drying and dissection of muscle biopsy
      specimens reduced the variation in the determination of muscle potassium and
      magnesium content. The total coefficient of variation was 8.6% in the dry
      determination of muscle potassium content and 13.5% in the wet determination (P <
      0.05). In the determination of muscle magnesium content, the total coefficient of
      variation was 7.4% in the dry determination and 13.7% when determined wet (P <
      0.005). Muscle sodium content had a very large coefficient of variation,
      independent of the method used. The content of dry solids was too high in
      biopsies which were incubated in Tris-vanadate buffer (31.9%), compared to
      biopsies which were not incubated in Tris-vanadate buffer (24.9%, P < 0.001).
      Hereby, the measured ouabain binding capacity became too high when measured wet.
      In conclusion, muscle electrolyte content and ouabain binding capacity should be
      determined after drying and microdissection of the biopsies, because this method
      confers the least variation and the highest accuracy.

PMID- 9657882
TI  - Spontaneous hydrolysis and dehydration of dehydroascorbic acid in aqueous
      solution.
AB  - The interaction of water with dehydroascorbic acid was examined by incubating
      dehydroascorbic acid and ascorbic acid in 18O-labeled water for various amounts
      of time and then oxidizing the products with hydrogen peroxide or reducing the
      products with mercaptoethanol, with analysis by gas chromatography mass
      spectrometry. Based on mass changes, dehydroascorbic acid readily exchanged three
      oxygen atoms with H218O. When mercaptoethanol was used to reduce dehydroascorbic
      acid (which had been incubated in H218O) to ascorbic acid, the newly formed
      ascorbic acid also contained three labeled oxygen atoms. However, ascorbic acid
      incubated in H218O for the same amount of time under identical conditions
      exchanged only two labeled oxygen atoms. Electron impact mass spectrometry of
      derivatized ascorbic acid created a decarboxylation product which had only two
      labeled oxygen atoms, regardless if 3-oxygen-labeled or 2-oxygen-labeled ascorbic
      acid was the parent compound, isolating the extra oxygen addition to carbon 1.
      These data suggest that dehydroascorbic acid spontaneously hydrolyzes and
      dehydrates in aqueous solution and that the hydrolytic-hydroxyl oxygen is
      accepted by carbon 1. Ascorbic acid, on the other hand, does not show this same
      tendency to hydrolyze.

PMID- 9657883
TI  - Inactivation of alpha1-proteinase inhibitor as a broad screen for detecting
      proteolytic activities in unknown samples.
AB  - The need for a quick, simple screening method for the detection of general
      proteolytic activity prompted us to determine whether cleavage within the
      reactive site loop region (RSL) of alpha1-proteinase inhibitor (alpha1-PI), a
      well-characterized member of the serpin family known to be susceptible to
      proteolytic inactivation, can be utilized for this purpose. Inactivation of
      alpha1-PI in the RSL region can be measured by loss of residual inhibitory
      capacity of alpha1-PI against its target proteinase. While we originally utilized
      this assay to detect a new proteinase from culture supernatants of Porphyromonas
      gingivalis, the feasibility of extending this assay to scan for proteolytic
      activity from other systems was also assessed. As an example, we found that the
      serine proteinase from Staphylococcus aureus (SSP) had virtually the same
      catalytic efficiency in inactivating alpha1-PI in our assay as it did in the
      hydrolysis of the synthetic substrate Z-Phe-Leu-Glu-pNA (kcat/Km value of 2 x
      10(4) M-1 s-1 vs 2.6 x 10(4) M-1 s-1, respectively). Additionally, in both assays
      activity could be readily detected in less than a 1 h incubation at SSP
      concentrations in the picomolar range. This assay is unique in that proteinases
      which hydrolyze peptide bonds within the RSL of alpha1-PI can readily be detected
      as measured by loss of alpha1-PI inhibitory activity.

PMID- 9657884
TI  - Quantitation and characterization of cytochrome c oxidase in complex systems.
AB  - Quantitation of cytochrome c oxidase in complex systems such as tissue
      homogenates is often hampered by the presence of other hemoproteins. Cyanide can
      bind to reduced cytochrome c oxidase from diverse sources with a dissociation
      constant in the range of 0.1-0.5 mM and induces a characteristic optical change.
      This contrasts with the very weak binding of cyanide to reduced forms of many
      other hemoproteins, including hemoglobin and myoglobin. Hence, difference spectra
      of cyanide binding to reduced samples can provide an improved method to resolve
      and quantitate cytochrome c oxidase. In addition, the cyanide compound of
      cytochrome c oxidase is photolabile. This property can be exploited to further
      enhance the sensitivity of detection and analysis of cytochrome c oxidase.

PMID- 9657885
TI  - Measurements of serotonin and related indoles using capillary electrophoresis
      with multiphoton-induced hyperluminescence.
AB  - We report the use of multiphoton-excited photochemistry to generate highly
      fluorescent products from hydroxyindoles fractionated in submicron capillary
      electrophoresis channels. In this approach, the near-infrared (750 nm) output
      from a modelocked titanium:sapphire laser is focused at the outlet of a 0.6
      micron i.d. capillary, producing pulse intensities of approximately 10(12) W cm-2
      within a femtoliter focal volume. Hydroxyindole molecules migrating through the
      outlet aperture of the capillary intersect the beam focus, where absorption of
      three to four photons (approximately 1.65 eV photon-1) initiates a photobleaching
      reaction. The resultant hydroxyindole photoproducts produce broadband visible
      emission (lambdamax approximately 500 nm) when excited with two additional near
      IR photons and appear substantially more resistant to photobleaching than the
      parent hydroxyindoles. This multiphoton-induced conversion of analytes to
      hyperluminescent derivatives thus offers a more sensitive approach than UV
      fluorescence for detecting extremely small quantities of material. Mixtures of
      the hydroxyindoles serotonin (5-hydroxytryptamine), 5-hydroxytryptophan, and 5
      hydroxyindole acetic acid are reliably characterized (relative error
      approximately 10%) in 100 s, with detection limits as low as approximately 70
      zmol (approximately 42,000 molecules). The sensitivity of this measurement
      strategy improves on the best previously reported results for capillary
      separations of indoles by more than one order of magnitude.

PMID- 9657886
TI  - Manually operated freeze-clamping press.

PMID- 9657887
TI  - A simple latex agglutination format for DNA probe-based tests.

PMID- 9657888
TI  - Colorimetric determination of chitosan.

PMID- 9657890
TI  - Call for papers: adolescents and risk-taking 
AB  - Copyright 1998 The Association for Professionals in Services for Adolescents.

PMID- 9657889
TI  - Two fluorometric approaches to the measurement of dextranase activity.

PMID- 9657891
TI  - Childhood stress, behavioural symptoms and mother-daughter pubertal development.
AB  - Belsky, Steinberg and Draper (Child Development 1991, 62, 647-670) predicted that
      early childhood stress or conflict in the family environment would be associated
      with childhood behavioural symptoms, early puberty and early, less discriminate
      sexual behaviour. Their theory was tested in a retrospective self-report survey
      in 28 daughters (aged 12 to 15) and 21 mothers. In daughters, earlier menarche
      correlated with more family stress in a late childhood (age 7 to 11); more
      conflict with mother in early childhood (birth to age 6); more rejection from and
      less closeness to mother throughout childhood (birth to age 11); more anxiousness
      and internalizing symptoms (anxiousness/depression) in late childhood (age 7 to
      11); earlier age at dating boys; and more boyfriends. An alternative
      interpretation is considered based on genetic transmission of maternal
      characteristics.

PMID- 9657892
TI  - Familial backgrounds and risk behaviors of youth with thrownaway experiences.
AB  - Many homeless youth may also be considered "thrownaway" in that they have
      specifically been told to leave home. In this study, thrownaway experiences among
      homeless youth are examined in two national samples: (a) a nationally
      representative sample of youth residing in youth shelters, and (b) a purposive
      sample of street youth in 10 cities. Prevalence of thrownaway experiences for the
      total samples and for demographic subgroups is provided, along with comparisons
      of the familial backgrounds and high-risk behaviors of youth with and without
      such experiences. In both samples, youth with thrownaway experiences (who
      constituted nearly half of each sample) were more likely than youth without such
      experiences to report (a) that they had attempted suicide, used marijuana and
      other drugs (excluding cocaine), and had been involved in the drug trade and
      carried hidden weapons; (b) that other family members had used illicit drugs
      during the 30 days before the youth left home; and (c) that they had spent at
      least 1 night away from home due to physical and/or emotional abuse or neglect,
      familial conflict, and familial substance use. Thrownaway youth constitute a
      particularly vulnerable subpopulation of homeless youth. A greater recognition
      and understanding of such youth will facilitate design of services that better
      address their needs.

PMID- 9657893
TI  - The effects of work and relational mental incongruity on identity formation and
      well-being.
AB  - By combining concepts of Tazelaar's mental incongruity theory (1983) and Marcia's
      identity model (1993) we tried to uncover some theoretical mechanisms that may
      underlie progressive developmental trends in identity status. Mental incongruity
      is what people experience when there is a discrepancy between how they think a
      situation should be (the standard) and how they experience the actual situation
      or their own behaviour (the cognition). In both the work and relational domain,
      the influence of adolescents' standards and mental incongruity on the development
      of their identity was studied. By means of structural equation modelling, we
      tested hypotheses on a representative sample of Dutch working adolescents, aged
      16 to 24 (n=706). As expected, a higher standard in the relational or work domain
      was related to more exploration and commitment in that domain - and thus to a
      more developed identity. Work and relational identity were positively related to
      well-being. Furthermore, positive relations were found between a standard and the
      mental incongruity in a domain. Finally, mental incongruities were negatively
      related to identity and only relational incongruity was negatively related to
      well-being.

PMID- 9657894
TI  - The acquisition, development and maintenance of lottery and scratchcard gambling
      in adolescence.
AB  - The U.K. National Lottery and instant scratchcards are now well established yet
      there is still little empirical research on the players. This study was an
      exploratory investigation of the psychosocial effects of these forms of gambling
      among adolescents (n=1195; aged 11- to 15-years-old). Using a questionnaire, it
      was shown that large numbers of adolescents were taking part in these activities.
      There was a significant link between parental and child gambling with most
      lottery tickets and scratchcards being bought for the adolescents by their
      parents. Results showed that many adolescents thought they would win lots of
      money on these activities and that these activities were in general not perceived
      to be forms of gambling. Six per cent of adolescents fulfiled the DSM-IV-J
      criteria for pathological gambling, the majority of which were males.

PMID- 9657895
TI  - Adolescents' and children's knowledge about rights: some evidence for how young
      people view rights in their own lives.
AB  - The present study examined the development of knowledge about rights from
      childhood to adolescence. One hundred and sixty-nine 8-16-year-olds participated
      in individual semi-structured interviews assessing knowledge and importance of
      rights both generally and in children's and adolescents' lives. Detailed content
      analyses indicated that a global stage account may not capture key features of
      the development of young people's knowledge about rights. Even the oldest
      adolescents consistently "defined" rights in concrete rather than abstract terms.
      In contrast, by 10 years of age the majority of subjects were aware of the
      universal nature of rights. These results suggest that what adolescents and
      children think about rights appears to be influenced by how they view rights in
      their own lives. The findings are discussed in terms of developmental theory and
      in relation to practical implications for children's rights.

PMID- 9657896
TI  - The relationship between early maltreatment and teenage parenthood.
AB  - In a longitudinal study of the effects of early childhood maltreatment, 92
      adolescents who had become parents while under 20 years of age were compared to
      297 adolescents who had not become parents during their teenage years. Preschool
      and school-age physical abuse alone and in combination with neglect were found to
      have significant relationships with teenage parenthood. Low self-esteem, as
      evaluated by elementary school teachers, was related to both early maltreatment
      and teenage parenthood. Sexual abuse, based on retrospective reports of the
      adolescents, had a significant but weaker relationship to teenage parenthood. The
      implications of these findings and the findings that high school dropout,
      assaultive behavior, and drug use are also related to teenage parenthood are
      discussed.

PMID- 9657897
TI  - Adolescents' perceptions of communication with parents relative to specific
      aspects of relationships with parents and personal development.
AB  - Adolescents' views of communication with their parents are examined in relation
      to measures of family satisfaction, adolescent decision-making and disagreement
      with parents (Study I), and to measures of self-esteem, well-being and coping
      (Study II). The results provide some support for the psychometric qualities of
      the Parent-Adolescent Communication Scale (PACS) and suggest that good family
      communication is associated with satisfaction with the family and with lack of
      disagreement between adolescents and parents. They also indicate a positive
      association between family communication and adolescent self-esteem, certain
      aspects of adolescent well-being and type of coping strategy employed.

PMID- 9657898
TI  - Identity status and empathic response patterns: a multidimensional investigation.
AB  - This study examined the multidimensional empathic response patterns of late
      adolescent undergraduate students according to their identity status. Subjects
      were 153 undergraduates at seven New York City area colleges. Subjects completed
      self-report measures of empathic response style and identity development.
      Empathic concern showed a statistically significant positive linear relationship
      with the identity status hierarchy. Cognitive empathy had a statistically
      significant positive relationship, and empathic distress had a statistically
      significant negative relationship with identity exploration. Findings are
      discussed in the context of developmental and social-cognitive models of identity
      status.

PMID- 9657900
TI  - Reviewers 
AB  - Copyright 1998 The Association for Professionals in Services for Adolescents.

PMID- 9657899
TI  - Brief report: the temperamental characteristics of the Chinese adolescents in
      Taiwan.
AB  - A Chinese Adolescent Temperament Self rating questionnaire was completed by 1165
      Chinese adolescents from high schools in or near Taipei City, Taiwan. Statistical
      analysis revealed the following results: (a) boys tended to show higher activity
      level, higher task orientation, higher intensity of reaction, higher tactile
      threshold and lower adaptability than girls; (b) junior graders tended to have
      lower rhythmicity, less initial approaching reaction toward new stimuli and lower
      adaptability than senior graders; (c) the eldest child tended to have higher
      adaptability, higher task orientation and higher rhythmicity than younger
      siblings in the family; and (d) those with a better educated father tended to
      have more positive mood, higher task orientation, higher adaptability, higher
      rhythmicity and more initial approaching reaction.

PMID- 9657901
TI  - The effect of ascorbic acid and ferric ammonium citrate on iron uptake and
      storage in lens epithelial cells.
AB  - Ferritin is the major intracellular iron storage protein which has been shown to
      protect cells against oxidative damage. Recent reports that an inherited
      abnormality in human ferritin synthesis is associated with early bilateral
      cataracts underscore the importance of understanding ferritin synthesis and iron
      storage in lens epithelial cells. We previously demonstrated that ascorbic acid
      greatly increases de novo synthesis of ferritin in lens epithelial cells. The
      objectives of the present study were to determine: (1) the effects of ascorbic
      acid and ferric ammonium citrate on iron uptake by canine lens epithelial cells
      from iron bound to transferrin and from ferric chloride and (2) the incorporation
      of this element into ferritin. Iron uptake by lens epithelial cells from 59ferric
      chloride was 20 times higher than from 59iron-transferrin and iron deposition
      into ferritin was 8-fold higher when 59ferric chloride was the source. Ascorbic
      acid had a stimulatory effect on iron uptake from transferrin and on
      incorporation of this element into ferritin. The ascorbic acid-induced increase
      of iron uptake required de novo protein synthesis but not specifically de novo
      ferritin biosynthesis. Although ferritin is not directly involved in iron uptake,
      the level of ferritin protein could control the pool of intracellular iron. The
      present results indicate that iron homeostasis in lens epithelial cells is
      affected mainly by changes in apoferritin synthesis, which is greatly stimulated
      by ascorbic acid, rather than by altering the rate of protein degradation, which
      is very slow in these cells under all circumstances. Ferric ammonium citrate
      activates iron uptake from transferrin in a wide range of cell lines by
      generation of free radicals. Ferric ammonium citrate also increased iron uptake
      from Tf in lens epithelial cells. Ferric ammonium citrate treated cells
      incorporated 5 times more iron and deposited 2 times more iron into ferritin than
      control cells. Increased incorporation of iron into ferritin was due to ferric
      ammonium citrate-induced stimulation of de novo ferritin synthesis rather than an
      increased rate of iron deposition into pre-existing ferritin. Ferric ammonium
      citrate had a different effect on iron uptake from ferric chloride; total iron
      uptake was not significantly increased while deposition into ferritin was
      significantly decreased. These results demonstrate that iron homeostasis in lens
      epithelial cells is regulated by ascorbic acid and by changes in the rate of de
      novo ferritin synthesis. In addition, the differences in iron uptake from
      transferrin and ferric chloride and its subsequent incorporation into ferritin
      suggests that the mechanisms by which iron is incorporated into ferritin are
      source dependent.

PMID- 9657902
TI  - ETA receptor mediated inhibition of intracellular pH regulation in cultured
      bovine corneal epithelial cells.
AB  - The contributions were determined in primary cultures of bovine corneal
      epithelial cells (BCEC) of Na:H exchange (NHE) and vacuolar H+-ATPase (i.e. V
      type) activity to the regulation of intracellular pH (pHi). Furthermore, we
      characterized the effects on pHi regulation of exposure to 1 microM ET-1 under
      control and acid loaded conditions. With the pH sensitive dye, 2',7' Bis
      (carboxyethyl)-5,6-carboxyfluorescein acetoxymethyl ester (BCECF-AM), the control
      pHi was 7.1 in NaCl (nominally HCO3-free) Ringers. Inhibition of NHE with 100
      microM dimethylamiloride (DMA) rapidly decreased pHi by 0.37 units. Similarly,
      selective inhibition of V-type H+-ATPase with 10 microM bafilomycin A1 decreased
      pHi by 0.22 units. Following acid loading in NaCl Ringers with a 20 mm NH4Cl
      prepulse, pHi recovery was partially inhibited by exposure to either Na-free
      (NMGCl) Ringers, 100 microM DMA or 20 microM bafilomycin A1. Based on decreases
      in H+ efflux resulting from selective inhibition of NHE and V-type H+ pump
      activity, NHE activity accounts for 76% of the pHi recovery following acid
      loading. Under control conditions, ET-1 (1 microM) had no effect on pHi whereas
      ET-1 completely suppressed pHi recovery following acid loading in NaCl or NMGCl
      Ringers. This inhibitory effect was largely due to stimulation of ETA because in
      the presence of BQ-123 (10 microM), a selective ETA receptor antagonist, pHi
      recovery was completely restored. Suppression of pHi recovery also occurred
      following stimulation of protein kinase C (PKC) with 10(-7) m phorbol myristate
      (PMA) whereas 10(-7) m 4 alpha phorbol 12,13 didecanoate (PDD) had no effect. ET
      1 failed to suppress pHi recovery after inhibition of PKC with 0.5 microM
      calphostin C suggesting that the inhibition of pHi recovery by ET-1 is a
      consequence of PKC stimulation. Similarly, inhibition of Ca2+-dependent
      calmodulin stimulated CaM II kinase with KN-62 (10 microM) reversed the
      suppression of pHi recovery by ET-1. Preinhibition of either protein phosphatase
      (PP), PP-1, PP-2A or PP-2B activity with 1 microM phenylarsine oxide, 10 nm
      okadaic acid, 10 microM cyclosporin A1 or 20 microM BAPTA, also obviated the
      suppression of pHi recovery by ET-1. Therefore ETA receptor mediated inhibition
      of pHi regulation following acid loading could be a consequence of either PKC or
      CaMII kinase stimulation. Each one of these kinases may in turn phosphorylate and
      thereby stimulate the activities of PP-1, PP-2A or PP-2B. An increase in the
      activity of any one of these protein phosphatases could lead to dephosphorylation
      of the NHE and V-type H+ pump. This alteration may prevent them from becoming
      adequately stimulated to elicit pHi recovery in response to acid loading.

PMID- 9657903
TI  - Hyalocyte-like cells are more numerous in the posterior chamber than they are in
      the vitreous of the rabbit eye.
AB  - The distribution and concentration of free cells inside the eye chambers of
      rabbits were investigated using semi-quantitative analysis of histological
      paraffin sections. Studies using light (methacrylate sections) as well as
      transmission and scanning electron microscopy were undertaken for the
      morphological characterization of the free cells. Immunocytochemistry and
      autoradiography were employed in an attempt to find out their nature and their
      origin, respectively. It was observed that cells morphologically similar to the
      vitreous hyalocytes were more numerous inside the posterior chamber than were the
      hyalocytes in the cortical vitreous. Neither the hyalocytes nor the posterior
      chamber cells reacted with an antibody to rabbit macrophages. The finding of
      labeled free cells after an intravitreal injection of 3H-thymidine indicates that
      these cells can renew themselves and that their number does not depend
      exclusively on monocytes migrating from the blood stream to the eye chambers, as
      is believed to occur. In conclusion, hyalocytes or hyalocyte-like cells are more
      concentrated in the posterior chamber than they are in the vitreous. Both the
      hyalocytes and the posterior-chamber cells could not be characterized as fully
      developed macrophages.

PMID- 9657904
TI  - Changes in the pupillary light reflex of pigmented royal college of surgeons rats
      with Age.
AB  - We studied the latency and amplitude of the pupillary light reflex response of
      the Royal College of Surgeons rat from 10 to 52 weeks of age. The responses of
      these dystrophic rats were diminished compared to those of normal, non-dystrophic
      rats at all ages examined. This was most marked at the dimmest light intensity
      studied here and for the latency of dystrophic animals' responses. The latency
      deteriorated over the course of 52 weeks, although there was some evidence of
      improvement beyond 36 weeks of age. The amplitude of the dystrophic animals'
      responses also suggested some deterioration occurring up to 36 weeks of age, but
      with a substantial improvement beyond this time. In addition to these parameters,
      we also observed a break in the constriction phase of the pupillary light reflex
      that was unique to the dystrophic animals' responses. The frequency with which
      the anomaly occurred decreased in a light-dependent manner with age. The
      improvement of the pupillary light reflex at older ages, even when very few
      photoreceptors remain, may reflect compensatory events occurring in the inner
      retinal layers and/or in the central connections of the pupillary light reflex
      pathway. We suggest that the break in the constriction phase is a reflection of
      dual inputs driving the response, one of which is affected more by the
      degenerative events. This study provides baseline data on the effect of
      degeneration on function over time which can be used to evaluate the efficacy of
      repair strategies such as transplantation.

PMID- 9657905
TI  - The effect of dexamethasone on integrin and laminin expression in cultured human
      trabecular meshwork cells.
AB  - Glucocorticoid treatment in vivo can produce a glaucoma similar in many ways to
      POAG. Treatment of trabecular meshwork cells in culture with dexamethasone allows
      the study of biochemical aspects of this disease process. The effects of
      dexamethasone on the expression of integrins and laminin in both normal and
      glaucomatous cultured human trabecular meshwork cells were evaluated. Human
      trabecular meshwork cell lines were cultured for 18 days in the presence or
      absence of 10(-7) m dexamethasone. Radioimmunoprecipitation was used to determine
      the relative expression of five alphaintegrin subunits. Laminin expression was
      evaluated with Western blots. Laminin was increased in all cell lines following
      dexamethasone treatment. alpha2, alpha5 and alphaV integrin chains showed
      consistent dexamethasone-induced changes in expression, while alpha3 and alpha4
      subunits did not. There were no differences in the expression patterns for any of
      these integrin subunits between normal and glaucomatous cell lines. Increased
      laminin deposition as seen in this study with dexamethasone treatment may be
      partially responsible for the decreased outflow facility seen in both steroid
      induced glaucoma and in POAG.

PMID- 9657906
TI  - Transforming growth factor-beta induced protein, betaIG-H3, is present in
      degraded form and altered localization in lattice corneal dystrophy type I.
AB  - Lattice corneal dystrophy type I (LCDI) is an inherited autosomal dominant local
      amyloidosis, restricted to the corneal stroma. Comparison of electrophoretic
      profiles of normal and dystrophic corneas revealed a 42 kD protein, which was
      present only in dystrophic corneas. The N-terminal sequence of this protein
      showed identity to transforming growth factor-beta induced gene product (betaIG
      H3). A polyclonal antiserum was raised in chicken against a synthetic peptide
      identical to the N-terminal portion of betaIG-H3. On immunoblots, the antiserum
      stained the 42 kD band, and also a 68 kD band corresponding to the reported
      molecular weight of the intact betaIG-H3. In normal corneas, only the 68 kD band
      was present. Immunohistologically, the antiserum stained corneal subepithelial
      regions, including subepithelial deposits, in dystrophic corneas. In normal
      corneas, the staining was observed only in the epithelium. These results may
      reflect the role of betaIG-H3 in extracellular matrix construction and/or amyloid
      formation.

PMID- 9657908
TI  - Recovery of corneal nerve morphology following laser in situ keratomileusis.
AB  - Morphological changes in the corneal nerves after laser in situ keratomileusis
      (LASIK) were investigated and the changes were compared with those observed after
      creation of the keratectomy flap without subsequent photoablation. After creating
      the hinged flap, a multizone excimer laser photoablation (myopic correction from
      6.00 to 6.66 D; diameter 6 mm) was performed on 27 rabbit corneas. Seven of these
      27 rabbits received an automated keratectomy without laser photoablation on the
      fellow eye. A histochemical acetylcholinesterase reaction was used to demonstrate
      the changes in the morphology of the corneal nerves 3 days, 2.5 and 5 months
      after the operations. In all specimens the deepest stromal nerve bundles showed
      normal morphology. Cut nerve trunks were found at the wound margins and at the
      level of the flap interphase in the stromal bed. At 3 days, both epithelial and
      basal epithelial/subepithelial nerves were found at the hinge of the flap but the
      rest of the flap showed a major loss of epithelial, basal
      epithelial/subepithelial and superficial stromal nerves. A few new regenerating
      thin nerve fibers were found to emerge from the cut stromal nerve trunks. They
      appeared to pass the wound margin into the flap area below the epithelium. At 2.5
      and 5 months an increasing number of regenerating nerve leashes were observed to
      emerge from the cut stromal nerve trunks. They appeared to send anastomosing
      fibers among the neighboring stromal nerves. By this time the epithelial, basal
      epithelial/subepithelial and anterior stromal innervation had gained an almost
      normal nerve density and architecture. In the corneas with the flap only, the
      epithelial innervation was slightly better spared in the center of the flap, and
      the stromal changes were somewhat less prominent compared with the LASIK corneas.

PMID- 9657907
TI  - Ciliary muscle capillaries have blood-tissue barrier characteristics.
AB  - It was determined whether the capillaries in the ciliary muscle are of the blood
      tissue barrier or of the permeable non-barrier type. Ciliary body and iris of
      normal human and animal eyes were examined by electron microscopy and by
      immunohistochemical staining with a panel of antibodies recognizing endothelial
      blood-brain barrier markers. In addition, horseradish peroxidase (HRP) tracer
      studies of the anterior segment were carried out in rabbits. Our results
      demonstrated that the capillary endothelium in human and rabbit ciliary muscle
      has few luminal pinocytotic vesicles and a morphological aspect suggesting the
      presence of tight junctions. Ciliary muscle and iris capillaries stained positive
      for the blood-brain barrier markers Glucose-Transporter-1 and P-Glycoprotein,
      while staining for the PAL-E antigen and the transferrin receptor was absent. In
      the rabbit ciliary muscle, vascular leakage of exogenous HRP tracer was absent.
      It was concluded that this functional barrier and the observed phenotype of
      ciliary muscle capillaries are consistent with a blood-tissue barrier function
      similar to that of the iris microvasculature.

PMID- 9657909
TI  - Expression of sialylated Lewisx gangliosides in cultured lens epithelial cells
      from rhesus monkey.
AB  - Monkey and human lenses contain essentially the same glycosphingolipids, and
      Lewisx and sialylated Lewisx epitopes are expressed on the terminal structure of
      neolactotetraosylceramide. However, monolayer cultures of lens epithelial cells
      from rhesus monkey expressed gangliosides GM3, GD3 and a small amount of GM1, but
      not sialylated Lewisx epitopes. Eight-week-old cultures on various extracellular
      matrices resulted in morphological changes in lens epithelial cells. Monolayer of
      cells cultured on vitronectin or polylysine assembled into aggregates after 4
      weeks of culture. Cells cultured on vitronectin expressed sialyl-Lewisx
      gangliosides and did not exhibit GD3. On collagens, fibronectin and laminin
      elongated cells were observed in cells cultured for 8 weeks. Thus, the
      interaction between cells and extracellular matrices influenced morphology and
      glycosphingolipid composition in lens epithelial cells.

PMID- 9657910
TI  - The relationship between osmotic stress and calcium elevation: in vitro and in
      vivo rat lens models.
AB  - Both in vivo and in vitro models were employed in the present study to assess the
      relative contribution of osmotic stress and increasing calcium levels to the
      development of sugar cataracts. In galactose cataract obtained from galactosemic
      weanling rats, the concentration of total calcium increased by nearly 10% at the
      first sign of visible opacification observed on the fourth day post-galactose
      feeding. After 7 days of galactose feeding, calcium levels continued to rise, to
      0.8 mM. During the first 10 days, loss of lens transparency and calcium elevation
      was gradual and steady, with precipitous changes occurring on days 11 and 12. In
      groups of rats where galactose feeding was stopped after 7 days, cataract
      reversal was followed during the next 5 weeks. During the initial first week of
      recovery, calcium influx and elevation in the lens continued but began to decline
      steadily thereafter. After 3 weeks of recovery, lens transparency had returned to
      almost normal. Calcium levels continued to decline and reached normal levels
      between day 34 and 42, nearly 4 weeks after removal of the galactose diet. The
      relationship between osmotic stress and calcium elevation was investigated more
      directly by culturing normal rat lenses in hypoosmotic medium (280 mOsm) to
      create osmotic gradients similar to that in galactosemic lenses. The results
      showed that during the first day of culture (12 hr), osmotically stressed lenses
      gained 3 mg of water, became opaque and gained excess calcium (7 mM compared to
      0.7 mM). Microscopic vacuoles appeared to accompany the process of opacification
      and contributed to increased light scattering and the loss of lens transparency.
      Additional experiments were designed to further distinguish between the effects
      of osmotic stress and calcium elevation on the opacification process. Thus,
      lenses were incubated in control and high-calcium medium (20 mM) at 300 mOsm.
      Within 12 hr of incubation, calcium elevation progressed to 1.37 mM, nearly
      doubling the normal value. Although opacification was observed in these lenses,
      no sign of vacuoles was evident. Collectively, the findings from this study
      support the premise that an early influx of calcium is brought about by osmotic
      stress and is responsible for the observed loss in transparency in osmotic
      (sugar) cataract.

PMID- 9657911
TI  - Temperature-sensitive interactions between RPE and rod outer segment surface
      proteins.
AB  - Phagocytosis of rod outer segments by the retinal pigment epithelium is
      distinguished by the two distinct temperature-dependent steps of binding and
      ingestion. This study was designed to see if retinal pigment epithelial (RPE)
      plasma membrane proteins interact with ROS plasma membrane proteins at
      temperatures favoring either binding or ingestion. A modified blot overlay assay
      was used whereby Western blots of RPE plasma membrane proteins were overlaid with
      biotinylated ROS plasma membrane proteins. RPE/ROS interactions were detected by
      streptavidin-HRP and the ECL method at 25 degrees C (ingestion), 15 degrees C
      (binding), and 4 degrees C (little or no binding or ingestion). Unlabeled ROS
      proteins served as the negative control. Competition with excess unlabeled ROS
      proteins were used to test the specificity of the protein interactions. Some
      protein interactions were somewhat temperature dependent. For example, two RPE
      plasma membrane proteins (200 kDa and 173 kDa) interacted with ROS plasma
      membrane proteins at both 25 degrees C and 15 degrees C, but not at 4 degrees C.
      A strongly labeled protein at 50 kDA protein was present at 25 degrees C but
      weakly labeled at 15 degrees C and at 4 degrees C. Other protein interaction were
      more clearly temperature dependent. For example, a 110 kDa RPE protein interacted
      with ROS proteins only at 25 degrees C. Another RPE protein (55 kDa) interacted
      only at 15 degrees C. These latter data provide correlations between binding
      events in the assay and previously described stages of phagocytosis.

PMID- 9657912
TI  - Rod outer segment maintenance is enhanced in the presence of bFGF, CNTF and GDNF.
AB  - We employed a morphological assay of outer segment collapse to determine if
      growth factors or other supplements directly affect dissociated rod
      photoreceptors in vitro. The morphological changes in outer segments were
      correlated with the light responsiveness of rods. Time-lapse video microscopy was
      used to observe the collapse of rod outer segments from isolated single cells and
      small clumps of cells. A consistent pattern of outer segment collapse into the
      inner segment was observed, yielding a convenient assay of the effects of
      neurotrophic factors on photoreceptor functional maintenance. The functional
      state of rods, defined as light-responsiveness, was measured with suction
      electrode recordings and matched with the various stages of outer segment
      collapse. Ciliary neurotrophic factor (CNTF) and glial cell-line-derived
      neurotrophic factor (GDNF) at a high concentration, yielded statistically
      significant improvements in rat outer segment survival times. Basic fibroblast
      growth factor (bFGF), which rescues photoreceptors in several rodent models of
      retinal degeneration, produced a significant increase in survival time in the
      presence of the cofactor heparin. In 4 out of 10 cases using human tisue, bFGF
      also yielded a significant increase in survival times. When brain-derived
      neurotrophic factor (BDNF) was applied to rat rods, outer segment survival times
      did not change. Outer segments collapsed more quickly when either pigment
      epithelial cell derived factor (PEDF) or sugar N-acetyl D-galactosamine (NAD-gal)
      were present. Our results show that rod photoreceptors can respond to bFGF, GDNF
      and CNTF in vitro and provide evidence for a direct effect of these neurotrophic
      factors on rods. The rapid collapse of isolated photoreceptors in this model
      provides a convenient means for testing various neurotrophic agents and the
      induced cellular responses.

PMID- 9657913
TI  - Serum-free media for culturing and serial-passaging of adult human retinal
      pigment epithelium.
AB  - The ability of a chemically-defined serum-free culture medium to support the
      attachment, growth and serial passaging of primary adult human retinal pigment
      epithelial (RPE) cells was studied. Primary cultures of adult human RPE were
      established in a chemically-defined serum-free culture medium on both bare or
      bovine corneal endothelial extracellular matrix-coated tissue-culture plastic.
      Confluent cells were serially passaged in chemically-defined serum-free culture
      medium three times by trypsinization, and trypsin activity was quenched with
      aprotinin. First passage RPE cells were plated onto tissue-culture plastic
      precoated with bovine corneal endothelial extracellular matrix or uncoated tissue
      culture plastic in 24 well plates at a density of 50 viable cells mm-2. Cells
      were maintained either in chemically-defined serum-free culture medium, DMEM
      without serum, or DMEM with 15% fetal bovine serum. For each medium plating,
      efficiencies were determined 24 hours after plating, and growth rates were
      determined on the first, third and seventh days after plating. Morphometric image
      analysis was performed on cells cultured for up to 6 weeks and three serial
      passages. Seeding efficiency on bovine corneal endothelial extracellular matrix
      coated tissue-culture plastic and treated tissue-culture plastic were higher for
      chemically-defined serum-free culture medium (88.9+/-2.7% and 47.1+/-4.1%,
      respectively) and DMEM with serum (87.2+/-5.6% and 52.9+/-10.5%, respectively)
      than DMEM without serum (59.2+/-5.6% and 33.1+/-6.9%, respectively; P<0.01). The
      RPE proliferation rate in chemically-defined serum-free culture medium was
      comparable to DMEM with serum on both substrates within the first 3 days,
      although cells in DMEM with serum had a higher proliferation rate on day 7. Cells
      cultured in DMEM without serum, eventually decreased in number. RPE maintained in
      chemically-defined serum-free culture medium maintained a consistent
      proliferation rate, reached confluence, and retained an epitheloid morphology on
      either extracellular matrix or tissue-culture plastic for up to 6 weeks and three
      serial passages. Primary RPE reached confluence at 12+/-3 days on bovine corneal
      endothelial extracellular matrix-coated tissue-culture plastic and 21+/-5 days on
      treated tissue-culture plastic. Confluent cultures were composed of small
      hexagonal cells with epitheloid morphology on both substrates. We concluded that
      primary adult human RPE can be cultured in this chemically-defined serum-free
      culture medium. RPE will proliferate, reach confluence, retain their epitheloid
      morphology and can be serially passaged in the absence of serum.

PMID- 9657914
TI  - Light stimulates tyrosine phosphorylation of rat rod outer segments In vivo.

PMID- 9657915
TI  - Announcements 

PMID- 9657916
TI  - Index 

PMID- 9657918
TI  - 10th International Congress of Immunology.
AB  - Copyright

PMID- 9657917
TI  - Retractions.

PMID- 9657919
TI  - Multifunctional cytokine expression by human coronary endothelium and regulation
      by monokines and glucocorticoids.
AB  - Human endothelium is capable of expressing a variety of molecules, including
      cytokines and growth factors, critical to inflammation. This aspect of coronary
      endothelium has not been studied in detail. In this study, we report, for the
      first time, expression of multifunctional cytokines by human coronary artery
      endothelial cells (HCAEC) and their regulation by inflammatory cytokines and
      glucocorticoids. We also compared expression of cytokine transcripts in two
      additional cell lines derived from pulmonary artery (HPAEC) and umbilical vein
      (HUVEC) endothelium. HCAEC expressed transcripts for interleukin 5 (IL-5), IL-6,
      IL-8, and monocyte chemotactic protein-1 (MCP-1) constitutively. Induction of IL
      1alpha, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), and MCP
      1 was seen following treatment with TNFalpha. We found no expression of IL-1RA,
      IL-2, IL-4, IL-13, TNF-alpha, or IFN-gamma in HCAEC. IL-1beta and TNF-alpha
      synergistically induced IL-6 and GM-CSF and additively induced IL-8 and MCP-1
      production, while IL-2, IL-10, IFN-alpha, and IFN-gamma had little or no
      additional effects. Interestingly, no IL-1alpha or IL-5 protein product was found
      even after maximal stimulation of HCAEC. No significant differences were seen in
      the profile of cytokine genes expressed by HCAEC, HPAEC, or HUVEC.
      Glucocorticoids inhibited IL-8 production from all three cell lines. This study
      demonstrates that human coronary endothelial cells are capable of expressing a
      wide variety of multifunctional cytokines which may be of relevance to vascular
      inflammation.

PMID- 9657920
TI  - A novel assay of angiogenesis in the quail chorioallantoic membrane: stimulation
      by bFGF and inhibition by angiostatin according to fractal dimension and grid
      intersection.
AB  - In a novel assay of angiogenesis in the quail chorioallantoic membrane (CAM), we
      measured vascular pattern and angiogenic rate after homogeneous exposure of the
      entire vascular tree to recognized modulators of vessel growth. In comparison to
      phosphate-buffered saline (PBS)-treated controls, the vascular stimulator, basic
      fibroblast growth factor (bFGF or FGF-2), increased the rate of angiogenesis by a
      maximum of 72%, whereas a recently discovered angiogenic inhibitor, angiostatin,
      decreased the rate of vascular growth by a maximum of 68%. The perturbants were
      applied in PBS to the CAM of 7-day-old embryos (E7) cultured in petri dishes, and
      the embryos were cultured further until fixation at E8 or E9. For morphometry of
      the quasi-two-dimensional CAM vasculature, digital images of arterial endpoints
      from the middle region of the CAM were acquired in grayscale at a magnification
      of 10x, binarized to black/white, and skeletonized. The pattern of vessel
      branching was assessed by measurement of the fractal dimension (Df), and vessel
      density (rhov), with the method of grid intersection. Correlations between these
      two statistical techniques were linear (r2 ranged from 0.967 to 0.985). For
      skeletonized images at E9, Df and rhov of bFGF-treated samples were 1.55 +/- 0.01
      and 782 +/- 26/cm2, respectively (relative to 1.49 +/- 0.02 and 583 +/- 60/cm2
      for controls), and of angiostatin-treated samples, 1.43 +/- 0.02 and 424 +/-
      74/cm2 (relative to 1.50 +/- 0.02 and 616 +/- 59/cm2 for controls). To establish
      normalization values for rates of angiogenesis, we analyzed untreated CAMs of E6
      to E12. From E7 to E10 in skeletonized images, Df increased linearly from 1.37 +/
      0.01 to 1.54 +/- 0.01 and rhov from 311 +/- 67 to 746 +/- 124/cm2 (in both
      cases, r2 = 1.000). Thus, the rates of normal angiogenic growth as measured by Df
      and rhov were 0.06/day and 138/cm2-day, respectively. From E10 to E12, Df and
      rhov declined slightly. Differences between the vasculature of untreated and PBS
      treated CAMs were statistically insignificant. In conclusion, vascular branching
      pattern and density in the quail CAM were stimulated by bFGF and inhibited by
      angiostatin. We quantified these changes with statistical significance by Df and
      rhov, which are expressed relative to the rates of normal developmental
      angiogenesis measured for the two parameters in untreated quail embryos.

PMID- 9657921
TI  - Ultrastructural study on the venous sphincter in the sublobular vein of the
      canine liver.
AB  - Although the existence of venous sphincters has been demonstrated in the
      sublobular veins of the canine liver, the role it plays in the regulation of
      liver blood flow is still uncertain. In the present study, I examined the fine
      structures of the venous sphincters treated with four kinds of drugs
      (epinephrine, histamine, isoproterenol, and histamine releaser) by conventional
      electron microscopy and by scanning electron microscopy using microvascular
      corrosion casts. Intravenous administration of epinephrine, histamine, and
      histamine releaser (compound 48/80) resulted in a strong constriction at the
      small branches (100-400 micron in caliber) of the sublobular veins, while the
      treatment with isoproterenol showed dilatation in the same branches. When treated
      with compound 48/80, both the endothelial-specific granules (Weibel-Palade
      granules) and the mast cell's granules of the sublobular veins showed swelling
      and became transparent reducing electron density. In contrast, the shape and
      electron density of the granules did not change when the veins were dilated. The
      results suggest that the small branches of the sublobular veins have extremely
      important functions for the regulation of the liver blood flow under normal
      conditions and that the component parts in the Weibel-Palade granules and/or mast
      cell's granules may be involved in the constriction of the sphincter muscles.

PMID- 9657922
TI  - Direct in vivo measurement of gastric microvascular pressures in the rat.
AB  - There are no direct data available on micropressures in the gastric
      microcirculation in spite of its pivotal role in the development of acute gastric
      mucosal lesions. Our goal was to develop an in vivo method to directly measure
      intravascular pressure and vessel diameter in various gastric microvessels. This
      paper describes methods and procedural details of our novel preparation of the
      exteriorized rat stomach for vascular micropuncture studies. The stomach of the
      anesthetized rat was fixed with minimal surgery in a temperature-controlled
      gastric chamber. Two preparations were used, both from the serosal side: a
      seromuscular preparation to study the circulation of superficial outer muscular
      layers and a submucosal preparation-following careful dissection of the
      seromuscular layer-to study the submucosal and deeper mucosal microcirculations.
      Intravascular hydrostatic pressure was measured with a servo-null micropressure
      measuring system, while vessel diameter was evaluated on the television screen
      with videometry. Data (average +/- SE) were obtained from muscular arterioles
      (20.8 +/- 0.93 micron; 29.8 +/- 1. 32 mmHg), venules (23.4 +/- 1.61 micron; 18.1
      +/- 0.61 mmHg), submucosal arterioles (50.9 +/- 3.55 micron; 55.4 +/- 2.78 mmHg),
      venules (53.7 +/- 2.06 micron; 21.4 +/- 0.73 mmHg), and deeper mucosal arterioles
      (20.2 +/- 1.06 micron; 33.8 +/- 0.81 mmHg), venules (29.9 +/- 1.17 micron; 25.8
      +/- 0.47 mmHg), at a systemic arterial pressure of 110 +/- 2.4 mmHg (n = 10 each
      from 14 animals). Further experiments demonstrated the applicability of this
      method to examine the effects of systemic blood pressure reduction and local
      application of vasoactive agents on the gastric microcirculation. This method is
      useful for analyzing the microcirculation of the stomach in vivo under different
      experimental conditions.

PMID- 9657924
TI  - Can low density lipoprotein influence microvascular caliber?
AB  - The intracellular free calcium concentration ([Ca2+]i) plays an important role in
      the regulation of vascular tone. In vascular smooth muscle cells (VSMCs) LDL
      causes changes in vascular tone by increasing [Ca2+]i. Pericytes are regarded as
      the microvascular counterpart of VSMCs and implicated in the regulation of
      microvascular cell biology under normal and pathological conditions (e.g.,
      diabetes mellitus, arterial hypertension, arteriosclerosis). For this reason
      pericytes and VSMCs were compared in their ability to increase [Ca2+]i after
      stimulation with LDL. Single VSMCs and pericytes were loaded with 2 microM of the
      Ca2+-sensitive dye Indo-1/AM. Fluorescence was recorded at 405 nm (Ca2+-bound)
      and 485 nm (Ca2+-free). Cells in suspension were loaded with 2 microM of the
      calcium ionophore FURA-2 AM (excitation wavelengths: 340 and 380 nm, emission 505
      nm). Basal [Ca2+]i levels were significantly higher in single pericytes (165 +/-
      38 nmol/L, n = 41) than in VSMCs (150 +/- 39 nmol/L, n = 40, P = 0.0038). In cell
      suspensions the following values were obtained: Pericytes (113 +/- 27 nmol/L, n =
      36) and VSMCs (109 +/- 26 nmol/L, n = 28), which are statistically not
      significant. For all concentrations of LDL used (except at 1 microg/ml n-LDL),
      the increase above basal values was significant and both cell types showed a
      clear dose-dependent reaction pattern. This study shows for the first time that
      pericytes and VSMCs increase their [Ca2+]i in a similar way after LDL
      stimulation. In analogy to aortic smooth muscle cells, our results indicate that
      LDL mediated [Ca2+]i changes in pericytes in the microvascular bed may cause
      vasoconstriction leading to impairment of blood flow in the microvasculature.

PMID- 9657923
TI  - In vivo neutralization of P-selectin inhibits leukocyte-endothelial interactions
      in retinal microcirculation during ocular inflammation.
AB  - P-selectin is one of the adhesion molecules involved in leukocyte rolling during
      an inflammatory reaction. The aim of this study was to examine the role of P
      selectin in leukocyte-endothelial interactions in retinal microcirculation during
      ocular inflammation, known as endotoxin-induced uveitis (EIU), in vivo. EIU was
      induced in Lewis rats by footpad injection of lipopolysaccharide (LPS). At the
      time of LPS treatment or 12 h later, anti-rat P-selectin mAb (ARP) was injected
      intravenously, and its effect on leukocyte behavior in the retina was studied
      after intravital staining with acridine orange using a scanning laser
      ophthalmoscope. P-selectin gene expression in the retina was also studied by a
      semiquantitative polymerase chain reaction (PCR) method. Administration of ARP at
      the time of LPS treatment significantly reduced the number of rolling leukocytes
      at 6 and 12 h by 68% (P < 0.05) and 83% (P < 0.01), respectively, and the number
      of cells infiltrating the vitreous at 48 h by 61% (P < 0.05). Interestingly, ARP
      significantly inhibited the vasodilation observed during EIU. In contrast,
      delayed administration of ARP blocked neither cellular infiltration nor
      vasodilation. P-selectin gene expression was upregulated during the course of
      EIU. In conclusion, P-selectin may significantly contribute to the development of
      inflammation in the early stage of endotoxin-induced ocular inflammation.

PMID- 9657925
TI  - A comparison of the microcirculation in the rat spinotrapezius and diaphragm
      muscles.
AB  - Of all skeletal muscles examined in the rat, the spinotrapezius (S) and diaphragm
      (D) have the closest fiber-type composition. However, their oxidative capacities
      differ by two- to threefold. We have developed an intravital microscopy
      preparation to study diaphragm microcirculation in vivo. Using this preparation
      and the standard spinotrapezius model first described by S. D. Gray (1973,
      Microvasc. Res. 5, 395-400), we tested the hypothesis that pronounced
      microcirculatory differences would exist between these two muscles as a function
      of their disparate oxidative capacities. The lineal density of all capillaries in
      the spinotrapezius was 33.6 +/- 1.5 compared to 65.1 +/- 3.3 capillaries/mm in
      the diaphragm (P < 0.001). In the diaphragm compared with the spinotrapezius
      muscle, a significantly (P < 0.05) greater proportion of capillary countercurrent
      flow (D, 29 +/- 6% vs 8 +/- 6%) existed. Within both muscles, there was a similar
      proportion of capillaries supporting red blood cell (RBC) flow (S, 89 +/- 7% vs
      D, 92 +/- 2%). However, the diaphragm supported significantly (P < 0.001) greater
      intracapillary RBC velocities (D, 302 +/- 11 vs S, 226 +/- 9 micron/s) and fluxes
      (D, 33.4 +/- 1.1 vs S, 19.2 +/- 2.1 cells/s) compared with the spinotrapezius.
      Capillary "tube" hematocrit was greater (P = 0.01) in the diaphragm (0.32 +/-
      0.02) than in the spinotrapezius (0.22 +/- 0.03) muscle. These data demonstrate
      that microcirculatory flow characteristics in resting muscle can be regulated
      independent of muscle fiber-type composition and may be related to muscle
      oxidative capacity.

PMID- 9657926
TI  - Growth factors reverse the impaired sprouting of microvessels from aged mice.
AB  - Aging is accompanied by impaired angiogenesis and deficient expression of several
      angiogenic growth factors. To test the hypothesis that replacement of these
      factors would improve angiogenesis in aged animals, we cultured microvessels
      derived from the epididymal fat pad of aged and young mice ("aged" and "young"
      microvessels) in three-dimensional collagen gels for 2 weeks and measured their
      sprouting (formation of branch points) in response to fetal bovine serum (FBS),
      endothelial cell growth supplement (ECGS), and the specific growth factors
      transforming growth factor-beta1 (TGF-beta1), vascular endothelial growth factor
      (VEGF), insulin-like growth factor-1 (IGF-1), and basic fibroblast growth factor
      (bFGF). In the presence of culture medium with 1% FBS (Minimal medium), sprouting
      of aged microvessels was significantly less than sprouting of young microvessels.
      The addition of high levels of FBS and ECGS to Minimal medium enhanced the
      sprouting of microvessels from aged mice to a greater degree than that of young
      mice, such that the difference between the two age groups was no longer
      significant. Formation of branch points by aged microvessels was also
      significantly increased by Minimal medium supplemented with TGF-beta1, bFGF, IGF
      1, or VEGF (listed in order of highest to lowest stimulation). Sprouts generated
      in the presence of VEGF possessed a particularly high percentage of endothelial
      cells. Mitomycin C did not diminish the degree of sprouting induced by TGF-beta1,
      VEGF, or IGF-1, a result indicating that early stages of angiogenesis, including
      formation of branch points, do not require cell division. From our findings in
      vitro, we propose that age-related deficiencies in angiogenesis in vivo are
      likely to be due, in part, to a decrease in angiogenic growth factors in the
      extracellular milieu.

PMID- 9657927
TI  - Factor V Leiden, mild hyperhomocyst(e)inemia and Buerger's disease.

PMID- 9657929
TI  - Initiation of DNA replication in phages and plasmids-a workshop summary.
AB  - Recent progress in understanding initiation mechanisms of DNA replication was
      discussed by some 30 speakers from Europe and U.S.A. in a workshop funded
      entirely by the Juan March Foundation of Madrid. Several speakers were
      postdoctoral associates and were selected from poster presenters. This was
      probably the first meeting at which phage and plasmid systems were given top
      billing together. The confluence was highly successful because of considerable
      overlap in strategies employed by the two systems. Mechanistic studies on DNA
      replication started with phage and the lessons learned have guided the thinking
      on eukaryotic DNA replication (Stillman, J. Biol. Chem. (1994) 269, 7047). The
      research on bacterial plasmids has also been pioneering in defining the
      principles of initiation control and has unraveled novel biological regulatory
      mechanisms such as antisense control.

PMID- 9657930
TI  - Genetic elements of Bacteroides species: a moving story.

PMID- 9657931
TI  - Kinetics of conjugative transfer: a study of the plasmid pXO16 from Bacillus
      thuringiensis subsp. israelensis.
AB  - The aggregation-mediated conjugation system of Bacillus thuringiensis subsp.
      israelensis, encoded by the 200-kb plasmid pXO16, is highly potent in
      transferring itself and efficient in mobilizing other nonconjugative plasmids.
      The present study reveals some salient features of this conjugation system. Our
      observations can be summarized as follows: (i) The conjugative transfer takes
      about 3(1/2) to 4 min. For a 200-kb plasmid this corresponds to about 1 kb per
      second. (ii) The ability to transfer the plasmid seems to be evenly distributed
      among the donors. (iii) Functionally, the mating complex was found to consist of
      one donor and one recipient cell, even though aggregates comprising thousands of
      interconnected cells are formed. (iv) Having donated the plasmid, the donor needs
      a "period of recovery" of about 10 min before it can redonate the plasmid. (v)
      Secondary transfer, i.e., transfer from newly formed transconjugants, is delayed
      about 40 min. This maturation time exceeds the generation time, and it may
      indicate that to display donor activity, a surface protein (the aggregation
      substance) has to be uniformly incorporated into the cell wall. Lastly, we found
      that when the experiments were sufficiently short and when the recipient cells
      were in excess compared with the donors, the process of conjugation could be
      reasonably described by a kinetic model analogous to the Michaelis-Menten model
      for enzyme catalysis. This allowed us to estimate (vi) the maximal conjugation
      rate to be about 0.05 transconjugant per donor per minute, and (vii) the Km
      value, i.e., the concentration of recipient that results in half of the maximal
      conjugation rate, to be about 4 x 10(6) recipients/ml.

PMID- 9657932
TI  - Characterization of a novel insertion sequence, IS1194, in Streptococcus
      thermophilus.
AB  - A novel insertion sequence, IS1194, has been identified in the lactic acid
      bacterium Streptococcus thermophilus CNRZ368. This 1200-bp element has 16-bp
      imperfect terminal inverted repeats. The single large open reading frame of this
      element encodes a 332-amino-acid protein that displays similarities with
      transposases encoded by bacterial insertion sequences belonging to the IS5 group
      of the IS4 family. A single copy of IS1194 was detected by hybridization in only
      2 of the 19 S. thermophilus strains tested and in 4 of the 13 Lactococcus lactis
      strains investigated. This suggests that this IS element was acquired by
      horizontal transfer. The unique IS1194 copy of S. thermophilus CNRZ368 is located
      in a region of at least 12 kb that was probably acquired by horizontal transfer
      from L. lactis. Furthermore, the IS1194 right end is identical to sequences found
      in a broad-host-range conjugative plasmid from Streptococcus pyogenes, pSM19035.

PMID- 9657933
TI  - Sequence analysis of plasmid pTF5, a 19.8-kb geographically widespread member of
      the Thiobacillus ferrooxidans pTFI91-like plasmid family.
AB  - The most important features of plasmid pTF5, a 19,793-bp plasmid that was
      isolated from Thiobacillus ferrooxidans ATCC33020, are presented. The plasmid
      contained at least 14 complete open reading frames (ORFs), most of which had
      clear amino acid sequence similarity to previously identified proteins. The
      majority of ORFs were related to proteins commonly found on plasmids such as
      replication-, partition-, and stability-associated proteins or on transposons
      such as transposases, an invertase, and a resolvase. Products of three of the
      ORFs were related to redox-active proteins and possibly constitute an electron
      transport system. Plasmids with restriction endonuclease maps identical to that
      of pTF5 have been widely reported among T. ferrooxidans strains, and in this
      study, pTF5 was itself shown to be a member of the widely distributed pTFI91 T.
      ferrooxidans plasmid family. A comparison of restriction endonuclease maps
      indicated that a pTFI91-like plasmid (9.8 kb) appeared to be contained entirely
      within pTF5.

PMID- 9657934
TI  - Identification of linear DNA plasmids of the yeast Pichia pastoris.
AB  - Two DNA plasmids, approximately 11 and 8 kb in size, have been identified in a
      strain of the yeast Pichia pastoris (Northern Regional Research Laboratories No.
      Y4290). The plasmids are resistant to RNase A and lambda exonuclease, but are
      sensitive to digestion by DNase I, suggesting that they are linear and double
      stranded DNA with 5'-protected ends. A restriction map has been constructed for
      the 11-kb plasmid, confirming that it is linear.

PMID- 9657935
TI  - Structural and functional properties of the hsp16.4-bearing plasmid pER341 in
      Streptococcus thermophilus.
AB  - The plasmid pER341 (2798 bp) of Streptococcus thermophilus ST134 was sequenced
      and its open reading frame (ORF) regions were characterized. Analysis of
      nucleotide sequences showed the putative translation product of ORF1 (rep)
      sharing a high level of homology with replication proteins of several small
      plasmids present in lactic acid bacteria and staphylococci. This and homology of
      regions of plus-strand (ORI) and minus-strand (ssoA) origin of replication with
      pC194-class plasmids indicated that pER341 replicates by the rolling-circle
      mechanism. ORF2 corresponded to a putative hsp gene that apparently encodes
      Hsp16.4, a 142-amino-acid heat stress protein. Hsp16.4 shared significant
      identity with other small, 18-kDa-class heat stress proteins from prokaryotic and
      eukaryotic sources. Hsp16.4 is apparently the first plasmidborne low-molecular
      weight heat stress protein reported in dairy fermentation bacteria with a
      potential role in temperature-regulated functions in S. thermophilus.

PMID- 9657936
TI  - Involvement of a 120-MDa plasmid of Azospirillum brasilense Sp245 in the
      production of lipopolysaccharides.
AB  - Using Omegon-Km mutagenesis, six Azospirillum brasilense Sp245 mutant derivatives
      lacking the capability to synthesize either one of the two major O-specific
      polysaccharides (O-PSs) were constructed in vivo. In all of the Lps mutants
      obtained, single Omegon-Km insertions were shown to be located on an indigenous
      plasmid DNA with molecular weight 120 MDa (p120). Physical and immunochemical
      analyses revealed two p120 loci coding for O-PSI and two p120 loci involved in
      the production of O-PSII. One of the lps loci from both groups was also shown to
      act in the production of Calcofluor-binding polysaccharides. It was demonstrated
      that two Sp245 plasmid bands with apparent molecular weights of 120 and 130 MDa
      (as visualized by analytical gel electrophoreses) seem to be the two topological
      forms of the same plasmid species (p120). Transfer properties of p120 were also
      examined.

PMID- 9657937
TI  - A plasmid family containing two different expression cassettes suitable for
      immunomodulation and genetic immunization.
AB  - We have developed an improved eukaryotic expression vector that consists of two
      distinct, complete, and differentially regulated transcription units. The
      peculiarities of this prototype vector, named pRC110, are represented by two
      different strong promoter/enhancer sequences, cytomegalovirus and Rous sarcoma
      virus, that independently drive transcription of two recombinant cDNAs, which may
      be easily cloned into specific rare restriction sites. Moreover, we describe a
      simple way to introduce an optimal translational start site context 5' to any
      peptide to be cloned in our vectors, thus allowing the correct and efficient
      expression of even a single part of a larger gene or a short synthetic peptide
      lacking its own AUG and neighboring regions. We demonstrate the in vivo
      expression efficacy of pRC110 for use in genetic vaccination through direct
      intramuscular gene transfer: specific antibodies are raised against one of the
      encoded peptides 3 weeks after muscle injection, and efficient transcription of
      the other syngeneic cDNA, mouse interleukin-2, is shown. The development of a
      "family" of vectors directly deriving from pRC110 is also described, with the
      common property that one of the encoded proteins may modulate the effects of the
      other. We recommend the use of pRC110 for genetic immunization and immunological
      response studies, when the concomitant local production of an immunogenic peptide
      and of a syngeneic immunomodulating cytokine is required.

PMID- 9657938
TI  - Retroviral matrix proteins: a structural perspective.

PMID- 9657939
TI  - Characterization of the thermosensitive ts453 reovirus mutant: increased dsRNA
      binding of sigma 3 protein correlates with interferon resistance.
AB  - The mutation harbored by the reovirus ts453 thermosensitive mutant has been
      assigned to the S4 gene encoding the major outer capsid protein sigma 3. Previous
      gene sequencing has identified a nonconservative amino acid substitution located
      near the zinc finger of sigma 3 protein in the mutant. Coexpression in COS cells
      of the sigma 3 protein presenting this amino acid substitution (N16K), together
      with the other major capsid protein mu 1, has also revealed an altered
      interaction between the two proteins; this altered interaction prevents the sigma
      3-dependent cleavage of mu 1 to mu 1C. This could explain the lack of outer
      capsid assembly observed during ts453 virus infection at nonpermissive
      temperature. In the present study, we pursued the characterization of this mutant
      sigma 3 protein. Although the N16K mutation is located close to the zinc finger
      region, it did not affect the ability of the protein to bind zinc. In contrast,
      this mutation, as well as mutations within the zinc finger motif itself, can
      increase the binding of the protein to double-stranded RNA (dsRNA). It also
      appears that the N16K mutant protein is more efficiently transported to the
      nucleus than the wild-type protein, an observation consistent with the postulated
      role of dsRNA binding in sigma 3 nuclear presence. The lack of association with
      mu 1, and/or the increased dsRNA-binding activity of sigma 3, could be
      responsible for a partial resistance of the ts453 virus to interferon treatment
      and this could have important consequences in the context of protein synthesis
      regulation during natural reovirus infection.

PMID- 9657940
TI  - Sulfatide inhibits HIV-1 entry into CD4-/CXCR4+ cells.
AB  - Sulfatide (3'sulfogalactosylceramide) is the natural sulfated derivative of
      galactosylceramide (GalCer), a glycosphingolipid receptor allowing HIV-1
      infection of CD4-negative cells from neural and intestinal tissues. The
      incorporation of exogenous sulfatide into the plasma membrane of HT-29 (a CD4
      /GalCer+/CXCR4+ human intestinal cell line) or RD (CD4-/GalCer-/ CXCR4+ human
      rhabdomyosarcoma) resulted in a dose-dependent inhibition of HIV-1 infection.
      Experiments with luciferase reporter viruses pseudotyped with HIV-1 or
      amphotropic murine leukemia virus envelopes demonstrated that sulfatide acts at
      the level of viral entry. Paradoxically, the transfer of sulfatide in the plasma
      membrane of various CD4- cells resulted in increased binding of HIV-1. Surface
      pressure measurements were conducted to study the interaction of gp120 with
      glycosphingolipid monolayers. The data showed that gp120 could penetrate into a
      monomolecular film of GalCer, confirming the role of this glycosphingolipid as a
      functional receptor for HIV-1. In contrast, the insertion of gp120 into a
      monolayer of sulfatide was very limited. Moreover, the incorporation of sulfatide
      in a monomolecular film of GalCer specifically inhibited the penetration of
      gp120. In conclusion, these data show that sulfatide mediates gp120 binding but,
      in marked contrast with GalCer, is not able to initiate the fusion event.

PMID- 9657941
TI  - Characterization of cucumber mosaic virus. V. Cell-to-cell movement requires
      capsid protein but not virions.
AB  - To ascertain the importance of amino-terminal proximal capsid protein (CP)
      sequences in cel-to-cell movement, virion formation, and stabilization, two CP
      mutants of cucumber mosaic virus (CMV) were generated by deletion of sequences
      encoding CP amino acids 15-40 (delta Sal-Nru) or 26-40 (delta Sac-Nru). Wildtype
      CMV and CMV containing delta Sac-Nru could infect systemically four host species,
      although symptoms induced by the two viruses usually were different CMV
      containing delta Sal-Nru could only infect Nicotiana benthamiana and N.
      clevelandii systemically, but only slowly, suggesting phloem-independent long
      distance movement. A variant mutant designated delta Sal-Nru* could systemically
      infect N. tabacum as well as the above two Nicotiana species, rapidly, but could
      not systemically infect Cucurbita pepo. Virus particles could not be detected in
      plants infected by delta Sal-Nru, while delta Sal-Nru* and delta Sac-Nru formed
      particles of lower stabilities than for wildtype virus. The CPs of delta Sal-Nru
      and delta Sal-Nru* could bind RNA in vitro, although less strongly than delta Sac
      Nru or wildtype CMV. These data indicate that amino-terminal proximal sequences
      of the CMV CP interact with viral RNA and are required for the formation of
      stable virions. Moreover, while the CP is necessary for cell-to-cell movement,
      the ability to form virions is not a prerequisite for cell-to-cell movement.

PMID- 9657942
TI  - Impaired activation and binding of the erythropoietin receptor by a mutant gp55
      of Friend spleen focus-forming virus, which has a cytoplasmic domain.
AB  - A murine erythroleukemogenic retrovirus, Friend spleen focus-forming virus,
      encodes an envelope protein-like membrane glycoprotein (gp55) in its defective
      env gene which is responsible for activation of the erythropoietin receptor
      (EpoR) and the abnormally rapid proliferation of erythroid precursor cells. The
      S34 mutant gp55, which possesses an additional cytoplasmic domain, is
      nonpathogenic and its processing to the cell surface is severely reduced compared
      to that of the wild-type gp55. In this study, we found that the S34 mutant gp55
      neither binds to nor activates the EpoR. The S34 mutant gp55 formed disulfide
      bonded homodimers in the rough endoplasmic reticulum (RER) membrane much less
      efficiently than the wild-type gp55, which is consistent with the proposal that
      homodimer formation is a prerequisite for gp55 to be exported from the RER. We
      found that the wild-type gp55 that is bound to EpoR in the RER consists of a
      large number of monomers and a small number of dimers, suggesting that monomers
      of the S34 mutant gp55 have lost the ability to bind to the EpoR. The 1-bp
      insertion present in the wild-type gp55 gene, causing a loss of the cytoplasmic
      domain, is essential for pathogenicity in that it renders the encoded protein
      capable of both binding to the EpoR and transport to the cell surface.

PMID- 9657943
TI  - The polyvalent staphylococcal phage phi 812: its host-range mutants and related
      phages.
AB  - Ninety-five percent of 782 culture collection strains, as well as hospital
      strains of Staphylococcus aureus subsp. aureus of different provenance and 43% of
      89 culture collection strains of different coagulase-negative species of the
      genus Staphylococcus, were found to be sensitive to the polyvalent phage phi 812
      or to at least one of its host-range mutants or to the polyvalent phages SK311,
      phi 131, and U16. Thus sensitivity to the polyvalent staphylococcal phages seems
      to be one of the common features of S. aureus subsp. aureus strains. The
      adsorption kinetics and one-step growth characteristics of the phages phi 812 and
      SK311 were estimated. Restriction genomic maps of the phages phi 812 (146.5 kb)
      and SK311 (141.1 kb) were constructed by use of the restriction endonucleases
      AvaII, PstI, KpnI, SacI, SmaI, and XhoI. The host-range mutations of the phage
      phi 812 were localized on this map. Comparison of restriction patterns of the
      phages phi 812 and SK311 with those of the polyvalent phages U16 and phi 131
      suggests that all these phages are closely related. Their genomes differ from
      each other mostly by some deletions, insertions (1-3 kb), or inversions. Evidence
      was given that the phage phi 812 together with SK311, phi 131, and U16 belongs in
      the phage species Twort, the description of which is substantially supplemented
      with the data on the phage phi 812 reported in this paper.

PMID- 9657944
TI  - Evidence that the RNA methylation and poly(A) polymerase stimulatory activities
      of vaccinia virus protein VP39 do not impinge upon one another.
AB  - Vaccinia protein VP39 has two RNA modifying activities. In monomeric form, it
      acts as an mRNA cap-specific 2'-O-methyltransferase, specifically modifying the
      ribose moiety of the first transcribed nucleotide of m7G-capped mRNA. In
      association with VP55, the catalytic subunit of the vaccinia poly(A) polymerase,
      VP39 facilitates the rapid elongation of poly(A) tails that are already greater
      than approximately 35 nt in length. Introducing new assays, we provide evidence
      that substrates for each of VP39's two activities do not detectably modulate the
      converse reaction and that VP39's 2'-O-methyltransferase activity is not
      significantly affected by its association with VP55. In an electrophoretic
      mobility shift assay, VP39 interacted with a short (5 nucleotide) RNA only when
      the latter was m7G-capped. Complexes with longer (22 nucleotide) RNAs were more
      stable (i.e., cap-independent) but were further stabilized by the presence of an
      m7G cap. An additional complex was observed at elevated RNA:protein molar ratios,
      indicating the presence of two RNA binding sites per VP39 molecule. Interaction
      at one of these sites was stabilized by the cap structure. Additional experiments
      indicated that RNA molecules undergoing poly(A) tail elongation by the VP55-VP39
      heterodimer are not favored as cap-methylation substrates.

PMID- 9657945
TI  - Pleiotropic effects of HIV-1 protein R (Vpr) on morphogenesis and cell survival
      in fission yeast and antagonism by pentoxifylline.
AB  - Expression of HIV-1 Vpr causes cell cycle G2 arrest, change in cell shape, and
      cell death over a large evolutionary distance ranging from human to yeast cells.
      As a step toward understanding these highly conserved Vpr functions, we have
      examined the effect of Vpr on cytoskeletal elements and the viability of fission
      yeast. We demonstrate that the changes in cell morphology induced by Vpr in
      fission yeast are caused by several underlying cellular abnormalities, including
      increased biosynthesis of chitin in the cell wall, disruption of the actin
      cytoskeleton, and altered polarity for cell growth. The extent of these cellular
      alterations and cell survival correlates with the level of vpr expression.
      Accompanying cell death, Vpr induces aberrant nuclear morphologies in fission
      yeast which are similar to those found during the apoptosis induced by Vpr in
      mammalian cells. The Vpr-induced cytopathic effects and cell death can be
      suppressed by treatment with pentoxifylline, a compound that inhibits HIV-1 viral
      replication and suppresses Vpr-induced cell cycle G2 arrest in human and fission
      yeast cells. The results presented here suggest that pentoxifylline suppresses
      the effects of Vpr by blocking interactions of Vpr with cellular proteins. Given
      that pentoxifylline has potential therapeutic value in blocking the effects of
      Vpr in HIV-infected patients, understanding the molecular mechanisms by which
      pentoxifylline antagonizes Vpr may have general implications for HIV therapy.

PMID- 9657946
TI  - Two new human T-lymphotropic virus type I phylogenetic subtypes in
      seroindeterminates, a Mbuti pygmy and a Gabonese, have closest relatives among
      African STLV-I strains.
AB  - Six new HTLV-I strains from seroindeterminate individuals were analyzed: four
      from Gabon, one from a Mbuti Efe pygmy in Congo (formerly Zaire), and one from a
      Congolese patient residing in Belgium. The LTR and env regions were sequenced and
      phylogenetic analyses were performed to characterize the new strains. Nucleotide
      divergence and phylogeny results showed that four of the new strains belong to
      the HTLV-Ib Central African subtype. The other two strains, one from the Efe
      pygmy and one from Gabon, lie on distinct branches of the LTR and env trees with
      respect to the four major HTLV-I subtypes. Despite the low bootstrap values,
      likelihood mapping analyses proved that these strains can be considered two new
      HTLV-I molecular subtypes, putatively named HTLV-Ie and HTLV-If. A relation
      exists in the phylogenetic trees and in the likelihood maps between the new
      subtypes and African STLV-I strains from Papio spp. and Cercopithecus spp.,
      suggesting one or more interspecies transmission events in the past. This study
      demonstrates that the phylogenetic subtyping of HTLV-I in the African continent
      is far from being completed and that samples presenting an indeterminate serology
      can potentially belong to new subtypes in humans. In addition, present day
      serological tests do not reliably type strains within the HTLV-Ib Central African
      subtype.

PMID- 9657947
TI  - Proteolytic mapping of the coronavirus infectious bronchitis virus 1b
      polyprotein: evidence for the presence of four cleavage sites of the 3C-like
      proteinase and identification of two novel cleavage products.
AB  - We have previously reported that the 3C-like proteinase of the coronavirus
      infectious bronchitis virus (IBV) is responsible for processing of the 1a and
      1a/1b polyproteins to three mature products of 24, 10, and 100 kDa (Liu et al.,
      1994, 1997; Ng and Liu, 1998). The C-terminal cleavage site of the 100-kDa
      protein was defined to be the Q891(1b)-S892(1b) dipeptide bond encoded by
      nucleotides 15,129 to 15,134 (Liu and Brown, 1995). In this report, other
      cleavage sites of the 3C-like proteinase in the polyprotein encoded by the ORF 1b
      region were mapped by coexpression, deletion, and site-directed mutagenesis
      studies. Using two ORF 1b-specific antisera, V58 and V17, three more Q-S(G)
      dipeptide bonds, encoded by nucleotides 16,929 to 16,934, 18,492 to 18,497, and
      19,506 to 19,511, respectively, were demonstrated to be the cleavage sites of the
      3C-like proteinase. Cleavage at these four positions would result in the release
      of four mature products with molecular masses of approximately 68, 58, 39, and 35
      kDa. Among them, the 39- and 35-kDa proteins were specifically identified in IBV
      infected cells. Taken together with the 100-kDa protein previously identified,
      these results suggest that the ORF 1b region of IBV mRNA1 may be able to encode
      five mature products.

PMID- 9657948
TI  - Mutations in the Exo III motif of the herpes simplex virus DNA polymerase gene
      can confer altered drug sensitivities.
AB  - Two herpes simplex virus mutants containing mutated residues within the conserved
      Exo III motif of the polymerase gene were previously shown to be defective in 3'
      5' exonuclease activity and exhibited extremely high mutation frequencies. In
      this study, we have shown that these mutants also exhibited higher resistance to
      phosphonoacetic acid and sensitivity to aphidicolin and all nucleoside analogs
      tested, including acyclovir and gangciclovir, compared to wild-type virus. Marker
      transfer experiments and sequencing analyses demonstrated that these altered
      phenotypes were the result of mutations within the Exo III motif. The data
      indicate that, aside from leading to exonuclease deficiency, mutations in the Exo
      III motif may also affect interaction of nucleoside triphosphates with the
      catalytic sites of polymerase activity.

PMID- 9657949
TI  - Varicella-zoster virus ORF61 deletion mutants replicate in cell culture, but a
      mutant with stop codons in ORF61 reverts to wild-type virus.
AB  - Varicella-zoster virus (VZV) ORF61 encodes a phosphoprotein that transactivates
      VZV promoters. Transfection of cells with cosmid DNAs, including a cosmid with a
      large deletion in ORF61, resulted in a VZV ORF61 deletion mutant that was
      impaired for growth in vitro and could be partially complemented by growth in
      neuroblastoma or osteosarcoma cell lines. Cells infected with the VZV ORF61
      deletion mutant expressed normal levels of an immediate-early VZV protein, but
      had reduced levels of a late protein and showed abnormal syncytia. Carboxy
      terminal truncation mutants of VZV ORF61 protein have a transrepressing phenotype
      and inhibit the infectivity of cotransfected wild-type viral DNA. Transfection of
      cells with cosmid DNAs, including a cosmid with stop codons that should result in
      an ORF61 truncation mutant expressing a transrepressing protein that retains the
      RING finger domain, resulted in a viral genome which reverted back to the wild
      type sequence. BAL-31 exonuclease was used to produce deletions at the site of
      the stop codons in ORF61 of the cosmid, resulting in loss of the RING finger
      domain. Transfection of tissue culture cells with the ORF61 BAL-31 deletion
      mutants and other cosmid DNAs yielded viable viruses. Thus, while deletion
      mutants lacking the RING finger domain of ORF61 replicate in cell culture, a
      mutant with stop codons that retains this domain could not be propagated and
      reverted to wild-type virus.

PMID- 9657950
TI  - Monoclonal antibody mapping of the envelope glycoprotein of the dengue 2 virus,
      Jamaica.
AB  - Although dengue (DEN) virus is the etiologic agent of dengue fever, the most
      prevalent vector-borne viral disease in the world, precise information on the
      antigenic structure of the dengue virion is limited. We have prepared a set of
      murine monoclonal antibodies (MAbs) specific for the envelope (E) glycoprotein of
      DEN 2 virus and used these antibodies in a comprehensive biological and
      biochemical analysis to identify 16 epitopes. Following domain nomenclature
      developed for the related flavivirus, tick-borne encephalitis, three functional
      domains were identified. Five epitopes associated with domain A were arranged in
      three spatially independent regions. These A-domain epitopes were destroyed by
      reduction, and antibodies reactive with these epitopes were able to block virus
      hemagglutination, neutralize virus infectivity, and block virus-mediated cell
      membrane fusion. Domain-A epitopes were present on the full-length E
      glycoprotein, a 45-kDa tryptic peptide representing its first 400 amino acids
      (aa) and a 22-kDa tryptic peptide representing at least aa 1-120. Four epitopes
      mapped into domain B, as determined by their partial resistance to reduction and
      the localization of these epitopes on a 9-kDa tryptic or chymotryptic peptide
      fragment (aa 300-400). One domain-B-reactive MAb was also capable of binding to a
      DEN 2 synthetic peptide corresponding to aa 333-351 of the E glycoprotein,
      confirming the location of this domain. Domain-B epitopes elicited MAbs that were
      potent neutralizers of virus infectivity and blocked hemagglutination, but they
      did not block virus-mediated cell-membrane fusion. Domains A and B were spatially
      associated. As with tick-borne encephalitis virus, determination of domain C was
      more problematic; however, at least four epitopes had biochemical characteristics
      consistent with C-domain epitopes.

PMID- 9657951
TI  - Genes and regulatory sites of the "host-takeover module" in the terminal
      redundancy of Bacillus subtilis bacteriophage SPO1.
AB  - Early in infection of Bacillus subtilis by bacteriophage SPO1, the synthesis of
      most host-specific macromolecules is replaced by the corresponding phage-specific
      biosyntheses. It is believed that this subversion of the host biosynthetic
      machinery is accomplished primarily by a cluster of early genes in the SPO1
      terminal redundancy. Here we analyze the nucleotide sequence of this 11.5-kb
      "host-takeover module," which appears to be designed for particularly efficient
      expression. Promoters, ribosome-binding sites, and codon usage statistics all
      show characteristics known to be associated with efficient function in B.
      subtilis. The promoters and ribosome-binding sites have additional conserved
      features which are not characteristic of their host counterparts and which may be
      important for competition with host genes for the cellular biosynthetic
      machinery. The module includes 24 genes, tightly packed into 12 operons driven by
      the previously identified early promoters PE1 to PE12. The genes are smaller than
      average, with half of them having fewer than 100 codons. Most of their inferred
      products show little similarity to known proteins, although zinc finger, trans
      membrane, and RNA polymerase-binding domains were identified. Transcription
      termination and RNase III cleavage sites were found at appropriate locations.

PMID- 9657952
TI  - The Maastricht strain and England strain of rat cytomegalovirus represent
      different betaherpesvirus species rather than strains.
AB  - The major immediate early (MIE) locus of the Maastricht strain of rat
      cytomegalovirus (RCMV) was found to comprise five exons of which the first is
      noncoding. The first three exons are spliced to either exon 4, generating IE1, or
      exon 5, generating IE2. An additional splicing event unique to RCMV (Maastricht)
      was identified in exon 5, resulting in a 466-bp deletion. IE1 transcripts were
      detected exclusively during the IE phase of infection in vitro, whereas IE2
      transcripts were detected during both the IE and late phase of infection. The
      similarities between amino acid sequences derived from the MIE gene of RCMV
      (Maastricht) and murine cytomegalovirus are low (22 and 37% for IE1 and IE2,
      respectively). Surprisingly, the similarities between the MIE proteins of RCMV
      (Maastricht) and the England strain of RCMV are also low (23 and 32% for IE1 and
      IE2, respectively). This suggests that these RCMV strains represent different
      betaherpesvirus species rather than strains. This is underscored by the
      difference between both viruses in genome size as well as growth characteristics.
      The existence of two different RCMV-like species might have important
      implications for the use of these viruses as models for human cytomegalovirus.

PMID- 9657953
TI  - Genome instability in BVDV: an examination of the sequence and structural
      influences on RNA recombination.
AB  - The cytopathogenic biotype of the pestivirus, bovine viral diarrhea virus, is
      frequently a product of nonhomologous recombination in the region of the genome
      encoding the viral NS2-NS3 proteins. The possibility that sequences or structures
      in this region contributed to a hotspot for RNA recombination was examined. A PCR
      based strategy was used to examine viral genomic RNA isolated from tissue samples
      of cattle persistently infected with the noncytopathogenic biotype of the virus.
      Analysis of two different regions of the viral genome revealed that recombination
      was not restricted to particular sequences. Alignment of the genomic sequences
      undergoing recombination and examination of the predicted secondary structures of
      the participating RNAs revealed that the dissociation of partial, newly
      synthesized negative strand RNAs from the positive strand template occurred at
      many different sites on the molecule. Similarly, it appeared that the
      reassociation of the RNA polymerase complex with a second positive strand
      template was frequently influenced by short regions of homology between the
      nascent RNA strand and open secondary structures in the template molecule.

PMID- 9657954
TI  - Infectious bursal disease virus changes the potassium current properties of
      chicken embryo fibroblasts.
AB  - Infectious bursal disease virus (IBDV) is the causative agent of an economically
      significant poultry disease. IBDV infection leads to apoptosis in chicken embryos
      and cell cultures. Since changes in cellular ion fluxes during apoptosis have
      been reported, we investigated the membrane ion currents of chicken embryo
      fibroblasts (CEFs) inoculated with the Cu-1 strain of IBDV using the patch-clamp
      recording technique. Incubation of CEFs with IBDV led to marked changes in their
      K+ outward current properties, with respect to both the kinetics of activation
      and inactivation and the Ca2+ dependence of the activation. The changes occurred
      in a time-dependent manner and were complete after 8 h. UV-treated noninfectious
      virions induced the same K+ current changes as live IBDV. When CEFs were
      inoculated with IBDV after pretreatment with a neutralizing antibody, about 30%
      of the cells showed a normal K+ current, whereas the rest exhibited K+ current
      properties identical to or closely resembling those of IBDV-infected cells.
      Incubation of CEFs with culture supernatant from IBDV-infected cells from which
      the virus particles were removed had no influence on the K+ current. Our data
      strongly suggest that the K+ current changes induced by IBDV are not due to virus
      replication, but are the result of attachment and/or membrane penetration.
      Possibly, the altered K+ current may delay the apoptotic process in CEFs after
      IBDV infection.

PMID- 9657955
TI  - Mechanisms of resistance of HIV-1 primary isolates to complement-mediated lysis.
AB  - Previous studies suggested that HIV-1 primary isolates (PI) were resistant to
      complement-mediated lysis (CML), while virus produced in certain T cell lines and
      virus taken directly from the plasma of HIV+ persons were both susceptible to
      CML. The purpose of this study was to investigate the mechanism(s) of PI
      resistance. PI were resistant to CML using pooled seropositive serum as an
      antibody source. Additionally, PI obtained from two patients at several times
      over 2 years were resistant to CML using autologous antibody. PI were also
      resistant to CML induced by monoclonal antibodies which neutralize a broad range
      of PI. Resistance to CML was associated with low binding of antibody to PI but
      was not due to low gp120 levels. Cell-line-derived virus and PI were equally
      sensitive to CML induced by antibody to host-cell proteins, suggesting that PBMC
      do not contribute properties to virions which make them more physically resistant
      to CML in general but that PI resistance is restricted to CML induced by
      antiviral antibody. These studies show that PI are resistant to CML mediated by
      various antiviral antibodies and indicate that low binding of antibody to virus
      is an important factor contributing to resistance.

PMID- 9657956
TI  - A baculovirus mutant defective in PKIP, a protein which interacts with a virus
      encoded protein kinase.
AB  - We have found that a temperature-sensitive mutant of the baculovirus AcMNPV,
      tsB97, is defective in PKIP, the product of ORF24 which was previously found to
      interact with and stimulate the activity of a virus-encoded protein kinase, PK-1.
      The mutant lacks the ability to form plaques and occlusion bodies at the
      nonpermissive temperature. The mutant displays several properties which suggest a
      defect in the latter half of the late phase of infection; these properties
      include a delay in the shutoff of host protein synthesis, the presence of
      aberrant electron-dense bodies associated with the virogenic stroma, and the
      production of few, if any, progeny budded virus. A study of the expression of
      selected late genes showed no difference in the timing or level of transcription
      or translation of most late genes. However, elevated levels of the late 6.9K
      protein, a protamine-like protein, were observed in mutant-infected cells at 24 h
      postinfection, suggesting a defect in the regulation of this protein. Two
      polypeptides, 40 and 6 kDa, exhibited considerably higher levels of steady-state
      phosphorylation in wt-infected cells versus tsB97-infected cells at 24 h p.i. and
      could be candidates for PK-1/PKIP-mediated phosphorylation. The tsB97 mutant also
      displayed a severe defect in very late gene transcription which accounts for its
      inability to form occlusion bodies. The effect of PKIP on very late gene
      transcription may be a secondary effect of the block in the late phase of
      infection. PKIP showed no ability to transactivate expression from a very late
      promoter in transient expression assays.

PMID- 9657957
TI  - Three closely related herpesviruses are associated with fibropapillomatosis in
      marine turtles.
AB  - Green turtle fibropapillomatosis is a neoplastic disease of increasingly
      significant threat to the survivability of this species. Degenerate PCR primers
      that target highly conserved regions of genes encoding herpesvirus DNA
      polymerases were used to amplify a DNA sequence from fibropapillomas and fibromas
      from Hawaiian and Florida green turtles. All of the tumors tested (n = 23) were
      found to harbor viral DNA, whereas no viral DNA was detected in skin biopsies
      from tumor-negative turtles. The tissue distribution of the green turtle
      herpesvirus appears to be generally limited to tumors where viral DNA was found
      to accumulate at approximately two to five copies per cell and is occasionally
      detected, only by PCR, in some tissues normally associated with tumor
      development. In addition, herpesviral DNA was detected in fibropapillomas from
      two loggerhead and four olive ridley turtles. Nucleotide sequencing of a 483-bp
      fragment of the turtle herpesvirus DNA polymerase gene determined that the
      Florida green turtle and loggerhead turtle sequences are identical and differ
      from the Hawaiian green turtle sequence by five nucleotide changes, which results
      in two amino acid substitutions. The olive ridley sequence differs from the
      Florida and Hawaiian green turtle sequences by 15 and 16 nucleotide changes,
      respectively, resulting in four amino acid substitutions, three of which are
      unique to the olive ridley sequence. Our data suggest that these closely related
      turtle herpesviruses are intimately involved in the genesis of
      fibropapillomatosis.

PMID- 9657958
TI  - The acidic domain of pUL37x1 and gpUL37 plays a key role in transactivation of
      HCMV DNA replication gene promoter constructions.
AB  - Transient complementation of human cytomegalovirus (HCMV) oriLyt DNA replication
      in permissive human diploid cells expressing replication genes under native
      promoters requires its UL36-38 gene products. Two of the immediate early (IE)
      proteins encoded by this locus, pUL37x1 and, to a lesser extent, gpUL37,
      activated expression of HCMV early gene promoter constructions. The other IE
      protein encoded by the UL36-38 locus, pUL36, and the early product, pUL38, did
      not transactivate the HCMV early promoter constructions under similar conditions.
      The acidic domain, common to both pUL37x1 and gpUL37, is required for activation
      of HCMV early promoter constructions. Conversely, gpUL37 sequences downstream of
      amino acid 199 are not required for transactivation of viral early promoters.
      Taken together, these results suggest that the requirement for UL36-38 products
      for HCMV DNA replication results, at least in part, from the requirement of the
      transactivation of HCMV early DNA replication promoters by pUL37x1 and, to a
      lesser extent, by gpUL37 and that the acidic domain is critical for this
      activity.

PMID- 9657959
TI  - Recombinant dengue virus type 1 NS3 protein exhibits specific viral RNA binding
      and NTPase activity regulated by the NS5 protein.
AB  - The full-length dengue virus NS3 protein has been successfully expressed as a 94
      kDa GST fusion protein in Escherichia coli. Treatment of the purified fusion
      protein with thrombin released a 68-kDa protein which is the expected molecular
      mass for the DEN1 NS3 protein. The identity of this protein was confirmed by
      Western blotting using dengue virus antisera. Two related activities of the
      recombinant NS3 protein were characterized, which were the binding of the protein
      to the 3'-noncoding region of the dengue virus RNA genome and NTPase activity. We
      demonstrated using a band shift assay that the DEN1 NS3 protein could form a
      complex with the stem-loop structure in the 3'-noncoding region (3'-NCR),
      although sites outside the stem-loop may also participate in binding. Using
      various unlabeled homopolymeric and heteropolymeric RNAs as competitors for
      binding, it was further shown that the DEN1 NS3 protein exhibits preferential
      binding to a 94-nt RNA transcript from the 3'-NCR of the dengue virus. The NTPase
      activity of the recombinant DEN1 NS3 protein was characterized using a thin-layer
      chromatography assay. We found that the DEN1 NS3 protein possesses some aspects
      of NTPase activity, which are distinct from those found in other flaviviruses.
      Although the NS3 protein was able to utilize all four ribonucleoside
      triphosphates as its substrates, the NS3 protein showed a distinct preference for
      purine triphosphates (i.e., ATP and GTP). The addition of poly(U) did not
      stimulate NTPase activity in DEN1 NS3 protein, which contrasts with the reports
      for other flaviviral NS3 proteins. However, NTPase activity was specifically
      stimulated by the viral NS5 protein, which was manifested by a more than twofold
      increase in the rate of ATP hydrolysis and a 25% increase in the yield of ADP at
      the end of a 120-min reaction. These data suggest that the NTPase activity of the
      NS3 protein may be regulated by the viral NS5 protein during virus replication.

PMID- 9657960
TI  - Chaperonins.
AB  - The molecular chaperones are a diverse set of protein families required for the
      correct folding, transport and degradation of other proteins in vivo. There has
      been great progress in understanding the structure and mechanism of action of the
      chaperonin family, exemplified by Escherichia coli GroEL. The chaperonins are
      large, double-ring oligomeric proteins that act as containers for the folding of
      other protein subunits. Together with its co-protein GroES, GroEL binds non
      native polypeptides and facilitates their refolding in an ATP-dependent manner.
      The action of the ATPase cycle causes the substrate-binding surface of GroEL to
      alternate in character between hydrophobic (binding/unfolding) and hydrophilic
      (release/folding). ATP binding initiates a series of dramatic conformational
      changes that bury the substrate-binding sites, lowering the affinity for non
      native polypeptide. In the presence of ATP, GroES binds to GroEL, forming a large
      chamber that encapsulates substrate proteins for folding. For proteins whose
      folding is absolutely dependent on the full GroE system, ATP binding (but not
      hydrolysis) in the encapsulating ring is needed to initiate protein folding.
      Similarly, ATP binding, but not hydrolysis, in the opposite GroEL ring is needed
      to release GroES, thus opening the chamber. If the released substrate protein is
      still not correctly folded, it will go through another round of interaction with
      GroEL.

PMID- 9657961
TI  - A 211-bp enhancer of the rat uncoupling protein-1 (UCP-1) gene controls specific
      and regulated expression in brown adipose tissue.
AB  - The uncoupling protein-1 gene is uniquely expressed in brown adipose tissue (BAT)
      and is positively regulated by cold exposure of animals and the sympathetic
      nervous system. To analyse the importance of a previously identified 211-bp
      enhancer [Cassard-Doulcier, Gelly, Fox, Schrementi, Raimbault, Klaus, Forest,
      Bouillaud and Ricquier (1993) Mol. Endocrinol. 7, 497-506] in the tissue-specific
      expression of this gene, transgenic mice were generated using the chloramphenicol
      acetyltransferase (CAT) gene as a reporter gene. One out of fourteen lines of the
      control transgenic mice bearing the Herpes simplex thymidine kinase (TK) promoter
      expressed weakly the CAT reporter gene in several tissues, whereas the other
      lines did not express CAT. Eight founders bearing the 211-bp enhancer-TK
      transgene were obtained. In six lines, no expression of CAT was detected. In one
      line, the expression of CAT was restricted to BAT. In another line, the
      expression of CAT was found in BAT and, to a lesser extent, in testis. Moreover,
      in these lines a marked and specific increase in the expression of the reporter
      gene in BAT was observed either after exposure of mice to the cold or by treating
      them with a beta-adrenoceptor agonist drug. These results demonstrate that the
      211-bp enhancer alone is sufficient to both direct and restrict expression to
      BAT. This enhancer also mediates the transcriptional response of the gene to beta
      adrenergic stimulation, although it does not contain conserved cAMP response
      element.

PMID- 9657962
TI  - Identification of a human homologue of the vesicle-associated membrane protein
      (VAMP)-associated protein of 33 kDa (VAP-33): a broadly expressed protein that
      binds to VAMP.
AB  - We report the identification of a human homologue of the vesicle-associated
      membrane protein (VAMP)-associated protein (hVAP-33) that has been implicated in
      neuronal exocytosis in Aplysia californica. This hVAP-33 shared 50% amino acid
      identity with the A. californica form and had similar length, structural
      organization and VAMP-binding abilities. However, in contrast with the neuron
      specific expression seen in A. californica, hVAP-33 was broadly expressed,
      suggesting possible roles in vesicle fusion in both neuronal and non-neuronal
      cells.

PMID- 9657963
TI  - Loss of the hepatic glycogen-binding subunit (GL) of protein phosphatase 1
      underlies deficient glycogen synthesis in insulin-dependent diabetic rats and in
      adrenalectomized starved rats.
AB  - Hepatic glycogen synthesis is impaired in insulin-dependent diabetic rats and in
      adrenalectomized starved rats, and although this is known to be due to defective
      activation of glycogen synthase by glycogen synthase phosphatase, the underlying
      molecular mechanism has not been delineated. Glycogen synthase phosphatase
      comprises the catalytic subunit of protein phosphatase 1 (PP1) complexed with the
      hepatic glycogen-binding subunit, termed GL. In liver extracts of insulin
      dependent diabetic and adrenalectomized starved rats, the level of GL was shown
      by immunoblotting to be substantially reduced compared with that in control
      extracts, whereas the level of PP1 catalytic subunit was not affected by these
      treatments. Insulin administration to diabetic rats restored the level of GL and
      prolonged administration raised it above the control levels, whereas re-feeding
      partially restored the GL level in adrenalectomized starved rats. The regulation
      of GL protein levels by insulin and starvation/feeding was shown to correlate
      with changes in the level of the GL mRNA, indicating that the long-term
      regulation of the hepatic glycogen-associated form of PP1 by insulin, and hence
      the activity of hepatic glycogen synthase, is predominantly mediated through
      changes in the level of the GL mRNA.

PMID- 9657964
TI  - DNA triple-helix formation on nucleosome-bound poly(dA).poly(dT) tracts.
AB  - We have used DNase I and hydroxyl-radical footprinting to examine the formation
      of intermolecular DNA triple helices on nucleosome-bound DNA fragments containing
      An.Tn tracts. We found that it is possible to form triplexes on these nucleosome
      bound DNAs, but the stability of the complexes depends on the orientation of the
      A tract with respect to the protein surface. Hydroxyl-radical cleavage of these
      complexes suggests that the DNA fragments are still associated with the
      nucleosome. However, the phased cleavage pattern is lost in the vicinity of the
      triplex, suggesting that the DNA has locally moved away from the protein surface.

PMID- 9657965
TI  - Interplay between cytoplasmic Ca2+ and the ATP/ADP ratio: a feedback control
      mechanism in mouse pancreatic islets.
AB  - In pancreatic beta cells, the increase in the ATP/ADP ratio that follows a
      stimulation by glucose is thought to play an important role in the Ca2+-dependent
      increase in insulin secretion. Here we have investigated the possible
      interactions between Ca2+ and adenine nucleotides in mouse islets. Measurements
      of both parameters in the same single islet showed that the rise in the ATP/ADP
      ratio precedes any rise in the cytoplasmic free-Ca2+ concentration ([Ca2+]i) and
      is already present during the initial transient lowering of [Ca2+]i produced by
      the sugar. Blockade of Ca2+ influx with nimodipine did not prevent the
      concentration-dependent increase in the ATP/ADP ratio produced by glucose and
      even augmented the ratio at all glucose concentrations which normally stimulate
      Ca2+ influx. In contrast, stimulation of Ca2+ influx by 30 mM K+ or 100 microM
      tolbutamide lowered the ATP/ADP ratio. This lowering was of rapid onset and
      reversibility, sustained and prevented by nimodipine or omission of extracellular
      Ca2+. It was, however, not attenuated after blockade of secretion by activation
      of alpha2-adrenoceptors. The difference in islet ATP/ADP ratio during blockade
      and stimulation of Ca2+ influx was similar to that observed between threshold and
      submaximal glucose concentrations. The results suggest that the following
      feedback loop could control the oscillations of membrane potential and [Ca2+]i in
      beta cells. Glucose metabolism increases the ATP/ADP ratio in a Ca2+-independent
      manner, which leads to closure of ATP-sensitive K+ channels, depolarization and
      stimulation of Ca2+ influx. The resulting increase in [Ca2+]i causes a larger
      consumption than production of ATP, which induces reopening of ATP-sensitive K+
      channels and arrest of Ca2+ influx. Upon lowering of [Ca2+]i the ATP/ADP ratio
      increases again and a new cycle may start.

PMID- 9657966
TI  - Insight into naphthoquinone metabolism: beta-glucosidase-catalysed hydrolysis of
      hydrojuglone beta-D-glucopyranoside.
AB  - In plants, the naphthoquinone juglone is known to be involved in pathogenic
      defence mechanisms, but it may also take part in plant developmental processes.
      This naphthoquinone can accumulate in a glycosylated form, namely hydrojuglone
      beta-d-glucopyranoside. The structural configuration of this compound was shown
      to be 1, 5-dihydroxy-4-naphthalenyl-beta-d-glucopyranoside by means of MS, NMR
      and nuclear Overhauser effect spectroscopy analyses. A hydrojuglone beta-d
      glucopyranoside beta-glucosidase (EC 3.2.1.21) was purified to homogeneity from
      Juglans regia L. The enzyme catalysed the release of juglone from hydrojuglone
      beta-d-glucopyranoside with high specificity and showed Michaelis-Menten kinetics
      with Km=0.62 mM and Vmax=14.5 microkat/mg of protein. This enzyme also showed a
      higher activity towards beta-d-fucosyl than beta-d-glucosyl bonds. The purified
      enzyme had an apparent Mr of 64000 by SDS/PAGE and a pI 8.9 by isoelectrofocusing
      PAGE. The purified enzyme was inhibited by several bivalent cations, such as
      Cu2+, Fe2+, Hg2+, and by d-glucono-1,5-lactone, showing non-competitive
      inhibition of the mixed type.

PMID- 9657967
TI  - Identification and purification of the reconstitutively active glutamine carrier
      from rat kidney mitochondria.
AB  - The glutamine carrier from rat kidney mitochondria, solubilized in dodecyl
      octaoxyethylene ether (C12E8) and partly purified on hydroxyapatite, was
      identified and completely purified by Celite chromatography. On SDS/PAGE, the
      purified glutamine carrier consisted of a single protein band with an apparent
      molecular mass of 41.5 kDa. When reconstituted into liposomes, the glutamine
      carrier catalysed both the unidirectional flux of glutamine and the
      glutamine/glutamine countertransport, which were completely inhibitable by a
      mixture of pyridoxal 5'-phosphate and N-ethylmaleimide. The carrier protein was
      purified 474-fold with a recovery of 58% and a protein yield of 0.12% with
      respect to the mitochondrial extract. The glutamine carrier-mediated transport is
      quite specific for l-glutamine. l-Asparagine is the only other amino acid that is
      efficiently transported by the reconstituted carrier protein. d-Glutamine, l
      glutamate and l-aspartate are very poor substrates. The transport activity was
      inhibited by several thiol-group and amino-group reagents.

PMID- 9657968
TI  - The cellular response to oxidative stress: influences of mitogen-activated
      protein kinase signalling pathways on cell survival.
AB  - The mammalian response to stress is complex, often involving multiple signalling
      pathways that act in concert to influence cell fate. To examine potential
      interactions between the signalling cascades, we have focused on the effects of a
      model oxidant stress in a single cell type through an examination of the relative
      influences of mitogen-activated protein kinases (MAPKs) as well as two proposed
      apoptosis regulators, nuclear factor kappaB (NF-kappaB) and Bcl-2, in determining
      cell survival. Treatment of HeLa cells with H2O2 resulted in a time- and dose
      dependent induction of apoptosis accompanied by sustained activation of all three
      MAPK subfamilies: extracellular signal-regulated protein kinase (ERK), c-Jun N
      terminal kinase/stress-activated protein kinase (JNK/SAPK) and p38. This H2O2
      induced apoptosis was markedly enhanced when ERK2 activation was selectively
      inhibited by PD098059. Apoptosis decreased when JNK/SAPK activation was inhibited
      by expression of a dominant negative mutant form of SAPK/ERK kinase 1. Inhibition
      of the p38 kinase activity with p38-specific inhibitors SB202190 and SB203580 had
      no effect on cell survival. Because NF-kappaB activation by H2O2 is potentially
      related to both the ERK and JNK/SAPK signalling pathways, we examined the effects
      of inhibiting the activation of NF-kappaB; this interference had no effect on the
      cellular response to H2O2. Overexpression of the anti-apoptotic protein Bcl-2
      significantly decreased the apoptosis seen after treatment with H2O2 without
      altering ERK or JNK/SAPK activities. Our results suggest that ERK and JNK/SAPK
      act in opposition to influence cell survival in response to oxidative stress,
      whereas neither p38 nor NF-kappaB affects the outcome. Bcl-2 acts independently
      and downstream of ERK and JNK/SAPK to enhance the survival of H2O2-treated cells.

PMID- 9657969
TI  - Acute desensitization of phospholipase C-coupled muscarinic M3 receptors but not
      gonadotropin-releasing hormone receptors co-expressed in alphaT3-1 cells:
      implications for mechanisms of rapid desensitization.
AB  - In the present study we have expressed the muscarinic M3 receptor in an
      immortalized mouse pituitary cell line (alphaT3-1), which expresses an endogenous
      gonadotropin-releasing hormone (GnRH) receptor, to examine potential differences
      in acute receptor regulation. Both of these receptors couple to the activation of
      phosphoinositide-specific phospholipase C (PLC) in these cells and we demonstrate
      that, despite expression in the same cell background, acute desensitization is a
      feature of muscarinic M3 receptors but not of GnRH receptors. We show that, when
      the concentrations of GnRH and methacholine are matched to give approximately
      equivalent maximal elevations of Ins(1,4,5)P3, the GnRH receptor is able to
      sustain PLC activity at the initial rate, whereas the muscarinic M3 receptor
      cannot. Thus PLC-activating G-protein-coupled receptors are able to undergo rapid
      desensitization in this cell line, indicating that the desensitization profile is
      receptor-specific rather than cell-specific. This argues strongly that post
      receptor regulatory features do not have a prominent role in mediating rapid
      desensitization in these cells. Furthermore GnRH receptor-mediated PLC activity
      is sustained despite a marked and persistent depletion in the steady-state level
      of PtdIns(4,5)P2. In contrast, activation of muscarinic receptors is not
      sustained despite only a transient decrease in PtdIns(4,5)P2 concentration. Thus,
      whereas the contribution of PtdIns(4,5)P2 depletion to the temporal profile of
      receptor-mediated PLC signalling has been difficult to assess, the present
      results demonstrate that this is unlikely to be of importance in these cells. We
      suggest that unique structural features of the GnRH receptor result in a lack of
      appropriate regulatory phospho-acceptor sites and that the absence of agonist
      dependent phosphorylation might underlie the lack of acute regulation.

PMID- 9657970
TI  - Developmental effect of polyamine depletion in Caenorhabditis elegans.
AB  - Ornithine decarboxylase (ODC) catalyses the conversion of ornithine to
      putrescine, an obligate precursor to the polyamines spermidine and spermine. We
      reported previously that homozygous odc-1 (pc13) worms have no detectable ODC
      activity. Despite their inability to make polyamines, these mutant worms appear
      normal, but with a slight reduction in total brood size, when grown in complex
      medium that presumably contains polyamines. We now show that when ODC-deficient
      worms are transferred to polyamine-free medium, they show a strong phenotype. odc
      1 worms have two different fates, depending upon the developmental stage at which
      polyamines are removed. If the polyamines are removed at the L1 larval stage, the
      mutant animals develop into adult hermaphrodites that produce very few or no
      eggs. In contrast, if mutant larvae at the later L4 stage of development are
      transferred to polyamine-deficient medium, they develop and lay eggs normally.
      However, approx. 90% of the eggs yield embryos that, although well
      differentiated, arrest at early stage 3. Either maternal or zygotic expression of
      ODC provides partial rescue of embryonic lethality. Supplementing deficient
      medium with the polyamine spermidine allows ODC-deficient worms to develop as on
      complex medium. Together, these findings suggest that ODC activity is most
      critically required during oogenesis and embryogenesis and, furthermore, that
      exogenous polyamines can override the requirement for ODC activity.

PMID- 9657971
TI  - Sequence, catalytic properties and expression of chicken glutathione-dependent
      prostaglandin D2 synthase, a novel class Sigma glutathione S-transferase.
AB  - The Expressed Sequence Tag database has been screened for cDNA clones encoding
      prostaglandin D2 synthases (PGDSs) by using a BLAST search with the N-terminal
      amino acid sequence of rat GSH-dependent PGDS, a class Sigma glutathione S
      transferase (GST). This resulted in the identification of a cDNA from chicken
      spleen containing an insert of approx. 950 bp that encodes a protein of 199 amino
      acid residues with a predicted molecular mass of 22732 Da. The deduced primary
      structure of the chicken protein was not only found to possess 70% sequence
      identity with rat PGDS but it also demonstrated more than 35% identity with class
      Sigma GSTs from a range of invertebrates. The open reading frame of the chicken
      cDNA was expressed in Escherichia coli and the purified protein was found to
      display high PGDS activity. It also catalysed the conjugation of glutathione with
      a wide range of aryl halides, organic isothiocyanates and alpha,beta-unsaturated
      carbonyls, and exhibited glutathione peroxidase activity towards cumene
      hydroperoxide. Like other GSTs, chicken PGDS was found to be inhibited by non
      substrate ligands such as Cibacron Blue, haematin and organotin compounds.
      Western blotting experiments showed that among the organs studied, the expression
      of PGDS in the female chicken is highest in liver, kidney and intestine, with
      only small amounts of the enzyme being found in chicken spleen; in contrast, the
      rat has highest levels of PGDS in the spleen. Collectively, these results show
      that the structure and function, but not the expression, of the GSH-requiring
      PGDS is conserved between chicken and rat.

PMID- 9657972
TI  - Chemical mechanism of the endogenous argininosuccinate lyase activity of duck
      lens delta2-crystallin.
AB  - The endogenous argininosuccinate lyase activity of duck delta2-crystallin was
      specifically inactivated by the histidine-specific reagent, diethyl
      pyrocarbonate. The protein was protected by l-citrulline or l-arginine from the
      diethyl pyrocarbonate inactivation. To characterize further the chemical
      mechanism of the delta2-crystallin-catalysed reaction, deuterium-labelled
      argininosuccinate was enzymically synthesized from fumarate and l-arginine with
      delta2-crystallin in 2H2O. The argininosuccinate synthesized contained about 19%
      of the anhydride form; however, the deuterium was clearly demonstrated to be
      incorporated enantioselectively. Only the pro-HR atom at C-9 of the succinate
      moiety was labelled in the [2H]argininosuccinate-9-d synthesized, which indicates
      an anti-elimination mechanism for the endogenous argininosuccinate lyase activity
      of delta2-crystallin. The enzymic activity of duck lens delta2-crystallin in the
      pH range 5.5-8.5 was investigated using both protium- and deuterium-labelled
      argininosuccinate as the substrate. From the logkcat versus pH plot, two
      molecular pKa values of 6.18+/-0.02 and 8.75+/-0.03 were detected in the delta2
      crystallin-argininosuccinate binary complex. The former must be dehydronated and
      the latter hydronated to achieve an optimum reaction rate. The logkcat/Km versus
      pH plot suggested two molecular pKa values of 5.96+/-0.09 and 8.29+/-0.10 for the
      free delta2-crystallin to be involved in the substrate binding. Small kinetic
      isotope effects of 1.17+/-0.02 and 1.05+/-0.09 were found for kcat and kcat/Km
      respectively. Combining results from labelling and kinetic analysis indicates
      that the endogenous argininosuccinate lyase activity of duck delta2-crystallin is
      compatible with a stepwise E1cB mechanism, the rate-limiting step probably at the
      C-N bond-cleavage step.

PMID- 9657973
TI  - Intestinal absorption of bile acids: paradoxical behaviour of the 14 kDa ileal
      lipid-binding protein in differential photoaffinity labelling.
AB  - Photoaffinity labelling of brush border membrane vesicles from rabbit ileum with
      radiolabelled 3,3-azo and 7,7-azo derivatives of taurocholate identified integral
      membrane proteins of molecular masses 93 and 46 kDa, as well as a 14 kDa
      peripheral membrane protein, as components of the ileal Na+/bile acid transport
      system [Kramer, Girbig, Gutjahr, Kowalewski, Jouvenal, Muller, Tripier and Wess
      (1993) J. Biol. Chem. 268, 18035-18046]. Differential photoaffinity labelling in
      the presence of non-radiolabelled bile acid derivatives led, as expected, to a
      concentration-dependent decrease in the extent of labelling of the 93 and 46 kDa
      transmembrane proteins, which are the monomeric and dimeric forms of the ileal
      bile acid transporter protein. The extent of labelling of the 14 kDa ileal lipid
      binding protein (ILBP), however, increased on the addition of unlabelled bile
      acids, the increase being dependent on the structure of the bile acid added. The
      possibility of artifacts was excluded by photoaffinity labelling experiments in
      the frozen state as well as by model calculations. The experimental results
      suggest that the binding of bile acids to ILBP can increase the affinity of ILBP
      for bile acids. These results would be in accordance with a substrate-load
      modification of transport activity and a positive-feedback regulation mechanism
      for active uptake of bile acid in the ileum.

PMID- 9657974
TI  - Induction of stress-activated protein kinases/c-Jun N-terminal kinases by the p55
      tumour necrosis factor receptor does not require sphingomyelinases.
AB  - Ceramide has been implicated in the activation of stress-activated protein
      kinases/c-Jun N-terminal kinases (SAPK/JNK). Binding of tumour necrosis factor
      (TNF) to its 55 kDa receptor (TR55) leads to the generation of ceramide through
      activation of either acid or neutral sphingomyelinase (A/N-SMase) as well as to
      potent activation of SAPK/JNK. We have examined a putative role of both N- and A
      SMase in the TR55-dependent activation of SAPK/JNK. The analysis of TR55 deletion
      mutants expressed in 70Z/3 pre-B cells revealed that activation of SAPK/JNK
      occurs independently of N-SMase. Although both SAPK/JNK and A-SMase are activated
      by the death domain of TR55, pharmacological prevention of the TR55-dependent
      activation of A-SMase, or proteolytic degradation of A-SMase in 70Z/3 cells, did
      not impair SAPK/JNK activation, indicating that SAPK/JNK are not secondary to A
      SMase. In addition, proteolytic degradation of A-SMase also did not affect
      SAPK/JNK activation by ultraviolet (UV-C) irradiation, arguing against a general
      role of A-SMase in stress-mediated responses. Furthermore, fibroblasts from
      Niemann-Pick A patients deficient in A-SMase did not show altered activation of
      SAPK/JNK in response to either TNF or UV-C. These results suggest that TR55 can
      activate SAPK/JNK without direct participation of sphingomyelinases or ceramide.

PMID- 9657975
TI  - Multidrug resistance transporter P-glycoprotein has distinct but interacting
      binding sites for cytotoxic drugs and reversing agents.
AB  - P-Glycoprotein, the plasma membrane protein responsible for the multidrug
      resistance of some tumour cells, is an active transporter of a number of
      structurally unrelated hydrophobic drugs. We have characterized the modulation of
      its ATPase activity by a multidrug-resistance-related cytotoxic drug,
      vinblastine, and different multidrug-resistance-reversing agents, verapamil and
      the dihydropyridines nicardipine, nimodipine, nitrendipine, nifedipine and
      azidopine. P-Glycoprotein ATPase activity was measured by using native membrane
      vesicles containing large amounts of P-glycoprotein, prepared from the highly
      multidrug-resistant lung fibroblasts DC-3F/ADX. P-Glycoprotein ATPase is
      activated by verapamil and by nicardipine but not by vinblastine. Among the five
      dihydropyridines tested, the higher the hydrophobicity, the higher was the
      activation factor with respect to the basal activity and the lower was the half
      maximal activating concentration. The vinblastine-specific binding on P
      glycoprotein is reported by the inhibitions of the verapamil- and the nicardipine
      stimulated ATPase. These inhibitions are purely competitive, which means that the
      bindings of vinblastine and verapamil, or vinblastine and nicardipine, on P
      glycoprotein are mutually exclusive. In contrast, verapamil and nicardipine
      display mutually non-competitive interactions. This demonstrates the existence of
      two distinct specific sites for these two P-glycoprotein modulators on which they
      can bind simultaneously and separately to the vinblastine site. The nicardipine
      stimulated ATPase activity in the presence of the other dihydropyridines shows
      mixed-type inhibitions. These dihydropyridines have thus different binding sites
      that interact mutually to decrease their respective, separately determined
      affinities. This could be due to steric constraints between sites close to each
      other. This is supported by the observation that vinblastine binding is not
      mutually exclusive with nifedipine or nitrendipine binding, whereas it is
      mutually exclusive with nicardipine. Moreover, verapamil binding also interacts
      with the five dihydropyridines by mixed inhibitions, with different
      destabilization factors. On the whole our enzymic data show that P-glycoprotein
      has distinct but interacting binding sites for various modulators of its ATPase
      function.

PMID- 9657976
TI  - Human mitochondrial phosphoenolpyruvate carboxykinase 2 gene. Structure,
      chromosomal localization and tissue-specific expression.
AB  - The mitochodrial (mt) phosphoenolpyruvate carboxykinase 2 (PCK2) gene was
      isolated by screening a human genomic library with a rat cytosolic (cy) PCK1 cDNA
      probe comprising sequences from exons 2-9 and by PCR amplification of human
      genomic DNA spanning consecutive exons with known primer pairs from mtPCK2 cDNA
      containing sequences from two putative neighbouring exons. The mtPCK2 gene spans
      approx. 10 kb and consists of ten exons and nine introns. All exon-intron
      junction sequences match the classical GT/AG rule. Northern blot analysis of
      poly(A)+ and total RNA from various tissues revealed one mRNA species of approx.
      2.4 kb. The gene is expressed in a variety of human tissues, mainly in liver,
      kidney, pancreas, intestine and fibroblasts. In contrast with the cytosolic
      isoenzyme, the mitochondrial form might not have a purely gluconeogenic function.
      The mtPCK2 gene maps to chromosome 14q11.2-q12, in contrast with the cyPCK1 gene
      located on 20q13.2-q13.31.

PMID- 9657977
TI  - Critical role of arg433 in rat transketolase activity as probed by site-directed
      mutagenesis.
AB  - It has been shown that one arginine per monomer at an unknown position is
      essential for enzyme activity of the homodimeric transketolase (TK) [Kremer, Egan
      and Sable (1980) J. Biol. Chem. 255, 2405-2410]. To identify the critical
      arginine, four highly conserved arginine residues of rat TK (Arg102, Arg350,
      Arg433 and Arg506) were replaced with alanine by site-directed mutagenesis. Wild
      type and mutant TK proteins were produced in Escherichia coli and characterized.
      The Arg102-->Ala mutant exhibited similar catalytic activity to the wild-type
      enzyme, whereas Arg350-->Ala, Arg506-->Ala and Arg433-->Ala mutants exhibited
      36.7, 37.0 and 6.1% of the wild-type activity respectively. Three recombinant
      proteins (wild-type, Arg350-->Ala and Arg433-->Ala) were purified to apparent
      homogeneity using Ni2+-affinity chromatography and further characterized. All
      these proteins were able to form homodimers (148 kDa), as shown by immunoblot
      analysis subsequent to non-denaturing gel electrophoresis. The Arg433-->Ala
      mutant protein was less stable than the wild-type and Arg350-->Ala proteins at 55
      degrees C. Kinetic analyses revealed that both Vmax and Km values were markedly
      affected in the Arg433-->Ala mutant. The Km values for two substrates xylulose 5
      phosphate and ribose 5-phosphate were 11.5- and 24.3-fold higher respectively.
      The kcat/Km values of the Arg433-->Ala mutant for the two substrates were less
      than 1% of those of the wild-type protein. Molecular modelling of the rat TK
      revealed that Arg433 of one monomer has three potential hydrogen-bond
      interactions with the catalytically important highly conserved loop of the other
      monomer. Thus, our biochemical analyses and modelling data suggest the critical
      role of the previously uncharacterized Arg433 in TK activity.

PMID- 9657978
TI  - Active Lyn protein tyrosine kinase is selectively enriched within membrane
      microdomains of resting platelets.
AB  - Circulating platelets are primed to respond very rapidly to thrombogenic stimuli,
      but most platelets complete their lifespan without ever becoming activated.
      Platelet activation is accompanied by waves of sequential tyrosine
      phosphorylation thought to involve members of the Src family of protein tyrosine
      kinases (PTKs). We show here that resting platelets contain highly active
      pp53/56(Lyn) PTK within membrane microdomains (rafts) isolated biochemically with
      or without the use of detergent. This fraction is also greatly enriched in the
      transmembrane glycoprotein CD36, known to associate with Lyn PTK, but in
      transfection studies we could find no evidence to suggest that CD36 affects the
      distribution or function of Lyn. Upon platelet activation Lyn activity remains
      constant or diminishes and pp60(c-src) PTK within this fraction becomes highly
      activated, indicating the dynamic nature of the membrane microdomains. It is
      suggested that the function of active Lyn PTK in the resting platelet is to allow
      prolonged survival of this anucleate cell.

PMID- 9657979
TI  - Distribution of the mevalonate and glyceraldehyde phosphate/pyruvate pathways for
      isoprenoid biosynthesis in unicellular algae and the cyanobacterium Synechocystis
      PCC 6714.
AB  - Isopentenyl diphosphate, the universal isoprenoid precursor, can be produced by
      two different biosynthetic routes: either via the acetate/mevalonate (MVA)
      pathway, or via the more recently identified MVA-independent glyceraldehyde
      phosphate/pyruvate pathway. These two pathways are easily differentiated by
      incorporation of [1-13C]glucose and analysis of the resulting labelling patterns
      found in the isoprenoids. This method was successfully applied to several
      unicellular algae raised under heterotrophic growth conditions and allowed for
      the identification of the pathways that were utilized for isoprenoid
      biosynthesis. All isoprenoids examined (sterols, phytol, carotenoids) of the
      green algae Chlorella fusca and Chlamydomonas reinhardtii were synthesized via
      the GAP/pyruvate pathway, as in another previously investigated green alga,
      Scenedesmus obliquus, which was also shown in this study to synthesize ubiquinone
      by the same MVA-independent route. In the red alga Cyanidium caldarium and in the
      Chrysophyte Ochromonas danica a clear dichotomy was observed: as in higher
      plants, sterols were formed via the MVA route, whereas chloroplast isoprenoids
      (phytol in Cy. caldarium and O. danica and beta-carotene in O. danica) were
      synthesized via the GAP/pyruvate route. In contrast, the Euglenophyte Euglena
      gracilis synthesized ergosterol, as well as phytol, via the acetate/MVA route.
      Similar feeding experiments were performed with the cyanobacterium Synechocystis
      PCC 6714 using [1-13C]- and [6-13C]-glucose. The two isoprenoids examined, phytol
      and beta-carotene, were shown to have the typical labelling pattern derived from
      the GAP/pyruvate route.

PMID- 9657980
TI  - Cloning of subunits of convulxin, a collagen-like platelet-aggregating protein
      from Crotalus durissus terrificus venom.
AB  - Convulxin (CVX) is a potent platelet-aggregating glycoprotein from the venom of
      the snake Crotalus durissus terrificus. It consists of two subunits, alpha and
      beta, joined by disulphide bridges in a hexameric structure. A cDNA library from
      venom gland was constructed in the vector pT3T7. The cloned cDNAs encoding the
      two chains of CVX were sequenced. Both are preceded by an identical 23-amino acid
      peptide signal sequence and encode sequences of 135 amino acids for the alpha
      chain and 125 amino acids for the beta chain. These polypeptides include a
      carbohydrate-recognition domain (CRD) in which some of the specific amino acids
      required for binding Ca2+ and galactose or mannose are absent. The presence of
      such a domain means that CVX can be included in the family of C-type lectins
      along with other snake venom proteins, although it is not a true lectin. Assuming
      that the localization of intracatenary disulphide bridges of each CVX chain is
      similar to that of the CRD and that an intercatenary bridge between the alpha and
      beta chains is similar to that of the C-type lectin botrocetin, we postulate the
      existence of an additional intercatenary bridge, which explains the tridimeric
      structure (alphabeta)3 of CVX.

PMID- 9657981
TI  - Refolding of urea-denatured adenylate kinase.
AB  - The refolding of urea-denatured adenylate kinase (EC 2.7.4.3) has been followed
      by formation of the secondary structure, change of surface hydrophobicity and
      recovery of catalytic activity. During refolding of adenylate kinase with a 20-80
      fold dilution of 4 M urea-denatured enzyme at 10 degrees C, the formation of the
      secondary structure is a fast process with a rate constant of >0.16 s-1.
      Transient enhancement of the 8-anilino-1-naphthalenesulphonate (ANS) fluorescence
      intensity is followed by a fluorescence decrease to the level equal to the value
      characteristic of native enzyme. The desorption of ANS binding fluorescence is
      relatively slow and can be fitted to a first order reaction with a rate constant
      of 0.004 s-1 when the ANS is present in the dilution buffer. The desorption of
      ANS-binding fluorescence is accelerated in the presence of nucleotide substrates.
      The rate constants are increased to 0.049, 0. 029, 0.028 and 0.029 s-1 in the
      presence of 1 mM AMP, MgATP, ATP and ADP respectively. The refolding rate
      constant calculated from the initial fluorescence intensity after mixing ANS with
      protein at different refolding intervals is 0.016 s-1, which is faster than those
      obtained when ANS is present throughout the refolding process, indicating that
      the binding of ANS with a partially folded intermediate retards its further
      refolding to its native structure. The reactivation rate is even faster than the
      rates of refolding monitored in the absence of substrates, showing that the
      refolding is accelerated in the presence of the substrates. A possible refolding
      pathway and the accelerating effect of substrates are discussed.

PMID- 9657982
TI  - Protection from oxidative inactivation of the 20S proteasome by heat-shock
      protein 90.
AB  - Heat-shock protein 90 (Hsp 90) has been implicated in both protection against
      oxidative inactivation and inhibition of the multicatalytic proteinase (MCP, also
      known as 20 S proteasome). We report here that the protective and inhibitory
      effects of Hsp 90 depend on the activation state of the proteasome. Hsp 90 (and
      also alpha-crystallin) inhibits the N-Cbz-Leu-Leu-Leu-MCA-hydrolysing activity
      (Cbz=benzyloxycarbonyl; MCA=7-amido-4-methylcoumarin) when the rat liver MCP is
      in its latent form, but no inhibitory effects are observed when the MCP is in its
      active form. Metal-catalysed oxidation of the active MCP inactivates the Ala-Ala
      Phe-MCA-hydrolysing (chymotrypsin-like), N-Boc-Leu-Ser-Thr-Arg-MCA-hydrolysing
      (trypsin-like; Boc=t-butyloxycarbonyl), N-Cbz-Leu-Leu-Glu-beta-naphthylamine
      hydrolysing (peptidylglutamyl-peptide hydrolase) and N-Cbz-Leu-Leu-Leu-MCA
      hydrolysing activities, whereas these activities are actually increased when the
      MCP is in its latent form. Hsp 90 protects against oxidative inactivation of the
      trypsin-like and N-Cbz-Leu-Leu-Leu-MCA-hydrolysing activities of the MCP active
      form, and alpha-crystallin protects the trypsin-like activity. The specificity of
      the Hsp 90-mediated protection was assessed by a quantitative analysis of the two
      dimensional electrophoretic pattern of MCP subunits before and after oxidation of
      the MCP, in the presence or absence of Hsp 90. Treatment of the FAO hepatoma cell
      line with iron and ascorbate was found to inactivate the MCP. Hsp 90
      overexpression obtained by challenging the cells with iron was associated with a
      decreased susceptibility to oxidative inactivation of the MCP trypsin-like
      activity. Depletion of Hsp 90 by using antisense oligonucleotides resulted in an
      increased susceptibility to oxidative inactivation of the MCP trypsin-like
      activity, providing evidence for the physiological relevance of Hsp 90-mediated
      protection of the MCP.

PMID- 9657983
TI  - Cloning of the gene and cDNA for hamster chymase 2, and expression of chymase 1,
      chymase 2 and angiotensin-converting enzyme in the terminal stage of
      cardiomyopathic hearts.
AB  - Chymase is responsible for the formation of angiotensin II, which plays crucial
      roles in the pathogenesis of cardiovascular diseases. In the present study we
      determined the gene organization of a novel hamster chymase (hamster chymase 2)
      and analysed the expression of chymase 1, chymase 2 and angiotensin-converting
      enzyme (ACE) in hamster hearts at the terminal stage of cardiomyopathy. The gene
      encoding hamster chymase 2 is 3.2 kb in length and has five exons and four
      intervening sequences. The overall organization of this gene is similar to that
      of several other serine proteases. The deduced amino acid sequence revealed the
      existence of a preproenzyme composed of a signal peptide with 19 amino acids, a
      propeptide with two amino acids and a catalytic domain with 226 amino acids. The
      predicted full sequence of the catalytic domain was revealed to be very similar
      to the sequences of mouse mast-cell protease 5 (86%), rat mast-cell protease III
      (85%) and human chymase (70%) and less similar to hamster chymase 1 (56%). The
      expression of chymase 1 in heart was higher than that of chymase 2. The cardiac
      chymase-like activity, as well as the mRNA levels of chymase 1 and 2 of BIO 14.6
      cardiomyopathic hamsters at the age of 60 weeks were increased 3.4-, 2.8- and 5.1
      fold respectively compared with age-matched BIO F1B control hamsters. The cardiac
      ACE activity and the ACE mRNA level of cardiomyopathic hamsters were also
      increased 4.1- and 2.4-fold compared with those of age-matched controls. These
      results suggest that up-regulation of both ACE and chymases participates in the
      pathophysiology of the terminal stage of cardiomyopathy.

PMID- 9657984
TI  - Cloning and thermostability of TaqI endonuclease isoschizomers from Thermus
      species SM32 and Thermus filiformis Tok6A1.
AB  - Two TaqI endonuclease (hereafter referred to as TaqI) isoschizomer genes, tsp32IR
      from Thermus species SM32 of Azores and tfiTok6A1I from T. filiformis Tok6A1 of
      New Zealand, were cloned in Escherichia coli. The overexpressed enzymes were
      partly purified and their thermostability was determined. In the medium-salt
      buffer, Tsp32IR, TfiTok6A1I and one previously cloned TaqI isoschizomer (TthHB8I)
      were more thermostable than TaqI. Tsp32IR remained partly active up to 90
      degreesC in the low-salt buffer. Six amino acid residues that are identical in
      the three high thermostability isoschizomers (Tsp32IR, TfiTok6A1I and TthHB8I)
      but differ in TaqI might provide added rigidity for thermostabilization. These
      include four proline residues located in or near loop regions, and one alanine
      and one arginine located at helix regions in the predicted TaqI endonuclease
      secondary structure. The possible role of these residues in thermostabilization
      was evaluated by mutagenizing the TaqI enzyme. Mutants generated at these six
      positions were less thermostable than wild-type TaqI. The results suggest that
      the surrounding sequence or structural context might be as important as the
      mutation itself.

PMID- 9657985
TI  - Identification of a domain in apolipoprotein B-100 that inhibits the procoagulant
      activity of tissue factor.
AB  - The ability of low-density lipoprotein (LDL) to inhibit the procoagulant activity
      of tissue factor is mediated by a direct protein-protein interaction involving
      apolipoprotein (apo) B-100. A lysine-rich sequence within apo B-100 (residues
      3121-3217), which we have termed lysine-rich apo B-100-derived (KRAD)-98 peptide,
      may be responsible for its activity. Within this region, residues 3147-3160 (KRAD
      14) contain an exceptionally high proportion of positive amino acids. Both
      recombinant KRAD-98 and KRAD-14 peptides inhibited the procoagulant activity of
      tissue factor by preventing the activation of factor VII. KRAD-14 also inhibited
      the prothrombinase components, factors Xa and V. In comparison with the parent
      protein (apo B-100), KRAD-14 peptide displayed a 20-fold enhancement in the rate
      of inhibition, whereas KRAD-98 peptide exhibited a rate closer to that of apo B
      100. Mutational analysis of KRAD-14 peptide revealed three adjacent amino acids,
      alteration of which greatly reduced the inhibitory potential of this peptide. A
      peptide derived from tissue factor (residues 58-66) was found to act co
      operatively with tissue factor itself, but also augmented the inhibition of
      tissue-factor activity by apo B-100. In conclusion, LDL may be a physiological
      regulator of haemostatic mechanisms through the interactions of lysine-rich
      domains of apo B-100 with tissue factor.

PMID- 9657986
TI  - Recombinant human endothelin-converting enzyme ECE-1b is located in an
      intracellular compartment when expressed in polarized Madin-Darby canine kidney
      cells.
AB  - Endothelin-converting enzyme (ECE) is a phosphoramidon-sensitive membrane-bound
      metalloprotease responsible for the conversion of big-endothelins into
      endothelins [Yanagisawa, Kurihara, Kimura, Tomobe, Kobayashi, Mitsui, Yazaki,
      Goto and Masaki (1988) Nature (London) 332, 411-415]. Several distinct isoforms
      of ECE have been cloned and identified. ECE-1a, b and c have the same ectodomain
      and differ only by their cytosolic tails [Schweizer, Valdenaire, Nelbock,
      Deuschle, Edwards, Stumpf and Loffler (1997) Biochem. J. 328, 871-877]. The
      ectodomain common to ECE-1 a, b and c shares extensive sequence similarities with
      neprilysin, a major kidney brush border metallopeptidase. To study the sorting of
      ECE in polarized cells, ECE-1bcDNA was expressed by transfection in polarized
      Madin-Darby canine kidney (MDCK) cells. Cell-surface biotinylation and
      immunofluorescence studies showed that ECE-1b is not expressed on the cell
      surface but was rather located in intracellular compartments that could also be
      labelled with anti-Rab-5 and Rab-7 antibodies and was thus tentatively identified
      as early and late endosomes. Similar results were also obtained when ECE-1b was
      expressed in non-polarized Chinese hamster ovary cells for comparison purposes.
      When MDCK or Chinese hamster ovary transfected cells were pre-treated with the
      ECE inhibitor phosphoramidon, a 3-fold increase in the level of ECE-1b was
      observed both by Western blotting and by enzymic activity. However, no change in
      the level of neprilysin or the beta-chain of meprin, two apical membrane
      metallopeptidases, was observed in MDCK cells transfected under similar
      conditions. Northern blotting showed that the increase in the level of ECE-1b was
      not owing to changes in the ECEmRNA transcription rate or stability. Rather,
      pulse-chase experiments followed by immunoprecipitation showed a decrease in the
      rate of degradation of ECE-1b in phosphoramidon-treated cells. Half-lives were
      determined to be 2.8 and 7.5 h for non-treated and phosphoramidon-treated cells,
      respectively. Confocal microscopy showed accumulation of ECE-1b immunoreactive
      material in the lysosomes of phosphoramidon-treated cells. Taken together, these
      results suggest that ECE-1b turns over very rapidly between endosomal and
      lysosomal compartments and that lysosomal degradation of the enzyme is slowed
      down by phosphoramidon.

PMID- 9657987
TI  - Biosynthesis of mucins in bovine trachea: identification of the major
      radiolabelled species.
AB  - Bovine trachea in organ culture secretes mucus containing a 'high-density' (1.46
      g/ml) and a 'low-density' (1.37 g/ml) mucin similar to those identified
      previously in bovine respiratory secretions [Hovenberg, Carlstedt and Davies
      (1997) Biochem. J. 321, 117-123]. After pulse-labelling, autoradiography showed
      uptake of [35S]sulphate by both epithelial goblet cells and submucosal glands,
      while [3H]proline was mainly incorporated into the ciliated surface epithelial
      cells. After 24 h of radiolabelling, neither the high- nor the low-density mucin
      in the secreted mucus gel was heavily radiolabelled with the precursors. In
      contrast, a population of molecules banding at 1.50 g/ml was heavily
      radiolabelled with [35S]sulphate. This component was smaller than the high
      density mucin from the mucus gel and was insensitive to reduction or digestion
      with chondroitin ABC lyase or heparan sulphate lyase. The molecules yielded two
      populations of high-Mr glycopeptides upon trypsin digestion, were sensitive to
      keratanase and endo-beta-galactosidase digestion and contained O-linked glycans.
      Extracts of the surface epithelium and submucosal tissue after radiolabelling
      showed that the high- and low-density mucins in the tissue were also poorly
      radiolabelled. Thus, under these conditions, the radiolabelled precursors were
      not effectively incorporated into the large oligomeric mucins but into a high-Mr
      monomeric species. This study suggests that data obtained in investigations where
      mucins are radiolabelled and studied without further separation into distinct
      components may rather reflect the turnover of this 'novel' monomeric species than
      the large oligomeric mucins.

PMID- 9657988
TI  - What's for dinner?: Entner-Doudoroff metabolism in Escherichia coli.

PMID- 9657989
TI  - Characterization of the maleylacetate reductase MacA of Rhodococcus opacus 1CP
      and evidence for the presence of an isofunctional enzyme.
AB  - Maleylacetate reductases (EC 1.3.1.32) have been shown to contribute not only to
      the bacterial catabolism of some usual aromatic compounds like quinol or
      resorcinol but also to the degradation of aromatic compounds carrying unusual
      substituents, such as halogen atoms or nitro groups. Genes coding for
      maleylacetate reductases so far have been analyzed mainly in chloroaromatic
      compound-utilizing proteobacteria, in which they were found to belong to
      specialized gene clusters for the turnover of chlorocatechols or 5
      chlorohydroxyquinol. We have now cloned the gene macA, which codes for one of
      apparently (at least) two maleylacetate reductases in the gram-positive,
      chlorophenol-degrading strain Rhodococcus opacus 1CP. Sequencing of macA showed
      the gene product to be relatively distantly related to its proteobacterial
      counterparts (ca. 42 to 44% identical positions). Nevertheless, like the known
      enzymes from proteobacteria, the cloned Rhodococcus maleylacetate reductase was
      able to convert 2-chloromaleylacetate, an intermediate in the degradation of
      dichloroaromatic compounds, relatively fast and with reductive dehalogenation to
      maleylacetate. Among the genes ca. 3 kb up- and downstream of macA, none was
      found to code for an intradiol dioxygenase, a cycloisomerase, or a dienelactone
      hydrolase. Instead, the only gene which is likely to be cotranscribed with macA
      encodes a protein of the short-chain dehydrogenase/reductase family. Thus, the R.
      opacus maleylacetate reductase gene macA clearly is not part of a specialized
      chlorocatechol gene cluster.

PMID- 9657990
TI  - The glycyl radical enzyme TdcE can replace pyruvate formate-lyase in glucose
      fermentation.
AB  - Mutants of Escherichia coli unable to synthesize a functional pyruvate formate
      lyase (PFL) are severely impaired in their capacity to grow by glucose
      fermentation. In a functional complementation assay designed to isolate the pfl
      gene from Clostridium butyricum, we fortuitously identified a gene that did not
      encode a PFL but nonetheless was able to complement the phenotypic defects caused
      by an E. coli pfl mutation. The clostridial gene encoded a basic 14. 5-kDa
      protein (TcbC) which, based on amino acid similarity and analysis of immediately
      adjacent DNA sequences, was part of a transposase exhibiting extensive similarity
      to the product of the site-specific transposon Tn554 from Staphylococcus aureus.
      Our studies revealed that the clostridial TcbC protein activated the
      transcription of the E. coli tdcABCDEFG operon, which encodes an anaerobic L
      threonine-degradative pathway. Normally, anaerobic synthesis of the pathway is
      optimal when E. coli grows in the absence of catabolite-repressing sugars and in
      the presence of L-threonine. Although anaerobic control of pathway synthesis was
      maintained, TcbC alleviated glucose repression. One of the products encoded by
      the tdc operon, TdcE, has recently been shown to be a 2-keto acid formate-lyase
      (C. Hesslinger, S. A. Fairhurst, and G. Sawers, Mol. Microbiol. 27:477-492, 1998)
      that can accept pyruvate as an enzyme substrate. Here we show that TdcE is
      directly responsible for the restoration of fermentative growth to pfl mutants.

PMID- 9657991
TI  - The apeE gene of Salmonella typhimurium encodes an outer membrane esterase not
      present in Escherichia coli.
AB  - Salmonella typhimurium apeR mutations lead to overproduction of an outer membrane
      associated N-acetyl phenylalanine beta-naphthyl ester-cleaving esterase that is
      encoded by the apeE gene (P. Collin-Osdoby and C. G. Miller, Mol. Gen. Genet.
      243:674-680, 1994). This paper reports the cloning and nucleotide sequencing of
      the S. typhimurium apeE gene as well as some properties of the esterase that it
      encodes. The predicted product of apeE is a 69.9-kDa protein which is processed
      to a 67-kDa species by removal of a signal peptide. The predicted amino acid
      sequence of ApeE indicates that it is a member of the GDSL family of serine
      esterases/lipases. It is most similar to a lipase excreted by the
      entomopathogenic bacterium Photorhabdus luminescens. The Salmonella esterase
      catalyzes the hydrolysis of a variety of fatty acid naphthyl esters and of C6 to
      C16 fatty acid p-nitrophenyl esters but will not hydrolyze peptide bonds. A rapid
      diagnostic test reported to be useful in distinguishing Salmonella spp. from
      related organisms makes use of the ability of Salmonella to hydrolyze the
      chromogenic ester substrate methyl umbelliferyl caprylate. We report that the
      apeE gene product is the enzyme in Salmonella uniquely responsible for the
      hydrolysis of this substrate. Southern blot analysis indicates that Escherichia
      coli K-12 does not contain a close analog of apeE, and it appears that the apeE
      gene is contained in a region of DNA present in Salmonella but not in E. coli.

PMID- 9657992
TI  - Identification of cpxR as a positive regulator essential for expression of the
      Shigella sonnei virF gene.
AB  - virF is the master regulator which activates the virulence determinant genes of
      Shigella spp. such as ipaBCD and virG. We previously reported that expression of
      virF itself is regulated in a pH-dependent manner and that cpxA, a sensor of a
      two-component regulatory system, is involved in this regulation (S. Nakayama and
      H. Watanabe, J. Bacteriol. 177:5062-5069, 1995). Disruption of cpxR, which has
      been thought to be the cognate response regulator of cpxA (J. Dong, S. Iuchi, H.
      S. Kwan, Z. Lue, and E. C. C. Lin, Gene 136:227-230, 1993), abolished virF
      expression almost completely. Purified CpxR bound directly to the upstream region
      of virF. Binding capacity was enhanced when CpxR was phosphorylated by
      coincubation with acetyl phosphate in vitro. Furthermore, we observed that
      phosphorylated CpxR could activate virF transcription in vitro. These results
      clearly indicated that CpxR was an essential activator for virF expression and
      strongly suggested that the binding of phosphorylated CpxR to the target site
      upstream of the virF gene induced a direct activation of virF transcription.

PMID- 9657993
TI  - Regulation of biosynthesis of individual cellulases in Thermomonospora fusca.
AB  - Regulation of the biosynthesis of the six cellulases comprising the cellulolytic
      system of the thermophilic soil bacterium Thermomonospora fusca ER1 was studied.
      The levels of the individual enzymes produced on different noninducing and
      inducing carbon sources were determined. The lowest level of cellulase synthesis
      (3 nM) was observed with xylose as a carbon source, and the highest level (247 to
      1,670 nM for different enzymes) was found in cultures grown on microcrystalline
      cellulose. Endocellulases and exocellulases showed distinctly different
      regulation patterns. Differences in the regulation of individual enzymes appear
      to be determined by the specific structural organization of the upstream
      regulatory sequences of their genes.

PMID- 9657994
TI  - Regulation of expression of GLT1, the gene encoding glutamate synthase in
      Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae glutamate synthase (GOGAT) is an oligomeric enzyme
      composed of three 199-kDa identical subunits encoded by GLT1. In this work, we
      analyzed GLT1 transcriptional regulation. GLT1-lacZ fusions were prepared and
      GLT1 expression was determined in a GDH1 wild-type strain and in a gdh1 mutant
      derivative grown in the presence of various nitrogen sources. Null mutants
      impaired in GCN4, GLN3, GAT1/NIL1, or UGA43/DAL80 were transformed with a GLT1
      lacZ fusion to determine whether the above-mentioned transcriptional factors had
      a role in GLT1 expression. A collection of increasingly larger 5' deletion
      derivatives of the GLT1 promoter was constructed to identify DNA sequences that
      could be involved in GLT1 transcriptional regulation. The effect of the lack of
      GCN4, GLN3, or GAT1/NIL1 was also tested in the pertinent 5' deletion
      derivatives. Our results indicate that (i) GLT1 expression is negatively
      modulated by glutamate-mediated repression and positively regulated by Gln3p- and
      Gcn4p-dependent transcriptional activation; (ii) two cis-acting elements, a
      CGGN15CCG palindrome and an imperfect poly(dA-dT), are present and could play a
      role in GLT1 transcriptional activation; and (iii) GLT1 expression is moderately
      regulated by GCN4 under amino acid deprivation. Our results suggest that in a
      wild-type strain grown on ammonium, GOGAT constitutes an ancillary pathway for
      glutamate biosynthesis.

PMID- 9657995
TI  - Expression of a gene for a porin-like protein of the OmpA family from
      Mycobacterium tuberculosis H37Rv.
AB  - An open reading frame in the genomic database of Mycobacterium tuberculosis H37Rv
      was identified as having homology with an outer membrane protein. We found that
      the gene specified a protein belonging to the OmpA family, which includes some
      porins of gram-negative organisms. The gene was amplified by PCR and cloned into
      Escherichia coli. Overexpression of the gene was toxic to the host, but limited
      amounts could be purified from cells before growth ceased. A truncated gene
      devoid of the code for a presumed signal sequence was well expressed, but the
      protein had no pore-forming activity in the liposome swelling assay. However, the
      intact protein, OmpATb, behaved as a porin of low specific activity, with a pore
      diameter of 1.4 to 1.8 nm, and was also active in planar lipid bilayers, showing
      a single-channel conductance of 700 pS. The protein had a molecular mass of about
      38 kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A polyclonal
      rabbit antiserum raised to the truncated protein recognized a protein of similar
      molecular mass in detergent extracts of broken M. tuberculosis cells. Reverse
      transcription-PCR confirmed that the gene for OmpATb was expressed in M.
      tuberculosis cells growing in culture. Comparison of the purified protein with
      that in the detergent-extracted preparation using liposomes and planar lipid
      bilayers showed that the two materials had similar pore-forming properties.
      OmpATb is different from either of the mycobacterial porins described so far.
      This is the first report of a porin-like molecule from M. tuberculosis; the porin
      is likely to be important in controlling the access of hydrophilic molecules to
      the bacterial cell.

PMID- 9657996
TI  - Dual promoters are responsible for transcription initiation of the fla/che operon
      in Bacillus subtilis.
AB  - The fla/che region contains more than 30 genes required for flagellar synthesis
      and chemotaxis in Bacillus subtilis, including the gene for the flagellum
      specific sigmaD factor, sigD. Sequence and primer extension data demonstrate that
      a PA promoter immediately upstream of flgB, henceforth referred to as the fla/che
      PA, and the PD-3 promoter are active in vivo. Transcription from the PD-3 element
      is dependent on sigmaD activity and is regulated by the flagellum-specific
      negative regulator, FlgM. In a strain containing a deletion of fla/che PA
      (PADelta), sigmaD protein was not detected, demonstrating that the fla/che PA is
      necessary for wild-type expression of the sigD gene. Thus, sigD is part of the
      >26-kb fla/che operon. Consistent with a lack of detectable sigmaD protein, the
      PADelta strain grows as long filaments and does not express a sigmaD-dependent
      hag::lacZ reporter construct. These phenotypes are indicative of a lack of sigD
      expression or complete inhibition of sigmaD activity by FlgM. However, sigmaD
      activity is found in a double mutant containing the PADelta and a null mutation
      in flgM. The double mutant no longer grows as long filaments, and expression of
      hag::lacZ is partially restored. These data demonstrate that a low level of
      sigmaD activity does exist in the PADelta mutant but can be detected only in the
      presence of a null mutation in flgM. Therefore, normal expression of sigD may
      also involve another promoter(s) within the fla/che operon.

PMID- 9657997
TI  - Roles of the carboxy-terminal half of Pseudomonas aeruginosa major outer membrane
      protein OprF in cell shape, growth in low-osmolarity medium, and peptidoglycan
      association.
AB  - OprF, the major outer membrane protein of Pseudomonas aeruginosa, is
      multifunctional in that it can act as a nonspecific porin, plays a role in the
      maintenance of cell shape, and is required for growth in a low-osmolarity
      environment. The latter two structural roles of OprF, and OprF's association with
      the peptidoglycan, have been proposed to be localized in the carboxy terminus of
      the protein, based on this region's similarity to members of the OmpA family of
      proteins. To determine if this is correct, we constructed a series of C
      terminally truncated OprF derivatives and examined their effects on P. aeruginosa
      cell length and growth in low-osmolarity medium. While the C terminus of OprF was
      required for wild-type cell length and growth in low-osmolarity medium,
      expression of the N terminus (first 163 amino acids [aa]) also influenced these
      phenotypes (compared with OprF deficiency). The first 154 to 164 aa of OprF
      seemed required for stable protein expression, consistent with the existence of a
      beta-barrel domain in the N terminus of OprF. Greater than 215 aa of the protein
      were required for strong peptidoglycan association, confirming that residues in
      the C-terminal end of OprF are required for peptidoglycan binding. OprF
      deficiency did not affect the in vivo growth of an OprF-deficient strain in a
      mouse chamber model. Collectively, these data suggest that the C terminus of OprF
      plays a role in cell length, growth of P. aeruginosa in low-osmolarity media (but
      not in vivo), and peptidoglycan association, while the N terminus has an
      influence on the first two characteristics and is additionally important for
      stable protein expression.

PMID- 9657998
TI  - Proposed signal transduction role for conserved CheY residue Thr87, a member of
      the response regulator active-site quintet.
AB  - CheY serves as a structural prototype for the response regulator proteins of two
      component regulatory systems. Functional roles have previously been defined for
      four of the five highly conserved residues that form the response regulator
      active site, the exception being the hydroxy amino acid which corresponds to
      Thr87 in CheY. To investigate the contribution of Thr87 to signaling, we
      characterized, genetically and biochemically, several cheY mutants with amino
      acid substitutions at this position. The hydroxyl group appears to be necessary
      for effective chemotaxis, as a Thr-->Ser substitution was the only one of six
      tested which retained a Che+ swarm phenotype. Although nonchemotactic, cheY
      mutants with amino acid substitutions T87A and T87C could generate clockwise
      flagellar rotation either in the absence of CheZ, a protein that stimulates
      dephosphorylation of CheY, or when paired with a second site-activating mutation,
      Asp13-->Lys, demonstrating that a hydroxy amino acid at position 87 is not
      essential for activation of the flagellar switch. All purified mutant proteins
      examined phosphorylated efficiently from the CheA kinase in vitro but were
      impaired in autodephosphorylation. Thus, the mutant CheY proteins are
      phosphorylated to a greater degree than wild-type CheY yet support less clockwise
      flagellar rotation. The data imply that Thr87 is important for generating and/or
      stabilizing the phosphorylation-induced conformational change in CheY.
      Furthermore, the various position 87 substitutions differentially affected
      several properties of the mutant proteins. The chemotaxis and
      autodephosphorylation defects were tightly linked, suggesting common structural
      elements, whereas the effects on self-catalyzed and CheZ-mediated
      dephosphorylation of CheY were uncorrelated, suggesting different structural
      requirements for the two dephosphorylation reactions.

PMID- 9657999
TI  - The D-xylose-binding protein, XylF, from Thermoanaerobacter ethanolicus 39E:
      cloning, molecular analysis, and expression of the structural gene.
AB  - Immediately downstream from the Thermoanaerobacter ethanolicus xylAB operon,
      comprising genes that encode D-xylose isomerase and D-xylulose kinase, lies a
      1,101-bp open reading frame that exhibits 61% amino acid sequence identity to the
      Escherichia coli D-xylose binding periplasmic receptor, XylF, a component of the
      high-affinity binding-protein-dependent D-xylose transport. The 25-residue N
      terminal fragment of the deduced T. ethanolicus XylF has typical features of
      bacterial leader peptides. The C-terminal portion of this leader sequence matches
      the cleavage consensus for lipoproteins and is followed by a 22-residue putative
      linker sequence rich in serine, threonine, and asparagine. The putative mature
      341-amino-acid-residue XylF (calculated molecular mass of 37,069 Da) appears to
      be a lipoprotein attached to the cell membrane via a lipid anchor covalently
      linked to the N-terminal cysteine, as demonstrated by metabolic labelling of the
      recombinant XylF with [14C]palmitate. The induced E. coli avidly bound D
      [14C]xylose, yielding additional evidence that T. ethanolicus XylF is the D
      xylose-binding protein. On the basis of sequence comparison of XylFs to other
      monosaccharide-binding proteins, we propose that the sequence signature of
      binding proteins specific for hexoses and pentoses be refined as
      (KDQ)(LIVFAG)3IX3(DN)(SGP)X3(GS)X(LIVA) 2X2A. Transcription of the monocistronic
      1.3-kb xylF mRNA is inducible by xylose and unaffected by glucose. Primer
      extension analysis indicated that xylF transcription initiates from two +1 sites,
      both situated within the xylAB operon. Unlike in similar transport systems in
      other bacteria, the genes specifying the membrane components (e.g., ATP-binding
      protein and permease) of the high-affinity D-xylose uptake system are not located
      in the vicinity of xylF in T. ethanolicus. This is the first report of a gene
      encoding a xylose-binding protein in a gram-positive or thermophilic bacterium.

PMID- 9658000
TI  - A region in the Bacillus subtilis transcription factor Spo0A that is important
      for spoIIG promoter activation.
AB  - Spo0A is a DNA binding protein in Bacillus subtilis required for the activation
      of spoIIG and other promoters at the onset of endospore formation. Activation of
      some of these promoters may involve interaction of Spo0A and the sigmaA subunit
      of RNA polymerase. Previous studies identified two single-amino-acid
      substitutions in sigmaA, K356E and H359R, that specifically impaired Spo0A
      dependent transcription in vivo. Here we report the identification of an amino
      acid substitution in Spo0A (S231F) that suppressed the sporulation deficiency due
      to the H359R substitution in sigmaA. We also found that the S231F substitution
      partially restored use of the spoIIG promoter by the sigmaA H359R RNA polymerase
      in vitro. Alanine substitutions in the 231 region of Spo0A revealed an additional
      amino acid residue important for spoIIG promoter activation, I229. This amino
      acid substitution in Spo0A did not affect repression of abrB transcription,
      indicating that the alanine-substituted Spo0A was not defective in DNA binding.
      Moreover, the alanine-substituted Spo0A protein activated the spoIIA promoter;
      therefore, this region of Spo0A is probably not required for Spo0A-dependent,
      sigmaH-directed transcription. These and other results suggest that the region of
      Spo0A near position 229 is involved in sigmaA-dependent promoter activation.

PMID- 9658001
TI  - Spo0A mutants of Bacillus subtilis with sigma factor-specific defects in
      transcription activation.
AB  - The transcription factor Spo0A of Bacillus subtilis has the unique ability to
      activate transcription from promoters that require different forms of RNA
      polymerase holoenzyme. One class of Spo0A-activated promoter, which includes
      spoIIEp, is recognized by RNA polymerase associated with the primary sigma
      factor, sigma A (sigmaA); the second, which includes spoIIAp, is recognized by
      RNA polymerase associated with an early-sporulation sigma factor, sigma H
      (sigmaH). Evidence suggests that Spo0A probably interacts directly with RNA
      polymerase to activate transcription from these promoters. To identify residues
      of Spo0A that may be involved in transcriptional activation, we used PCR
      mutagenesis of the entire spo0A gene and designed a screen using two
      distinguishable reporter fusions, spoIIE-gus and spoIIA-lacZ. Here we report the
      identification and characterization of five mutants of Spo0A that are
      specifically defective in activation of sigmaA-dependent promoters while
      maintaining activation of sigmaH-dependent promoters. These five mutants identify
      a 14-amino-acid segment of Spo0A, from residue 227 to residue 240, that is
      required for transcriptional activation of sigmaA-dependent promoters. This
      region may define a surface or domain of Spo0A that makes direct contacts with
      sigmaA-associated holoenzyme.

PMID- 9658002
TI  - Identification of a gene product induced by hard-surface contact of
      Colletotrichum gloeosporioides conidia as a ubiquitin-conjugating enzyme by yeast
      complementation.
AB  - The germinating conidia of many phytopathogenic fungi on hosts must differentiate
      into an infection structure called the appressorium in order to penetrate their
      hosts. Chemical signals, such as the host's surface wax or fruit ripening
      hormone, ethylene, trigger germination and appressorium formation of the avocado
      pathogen Colletotrichum gloeosporioides only after the conidia are in contact
      with a hard surface. What role this contact plays is unknown. Here, we describe
      isolation of genes expressed during the early stage of hard-surface treatment by
      a differential-display method and report characterization of one of these cloned
      genes, chip1 (Colletotrichum hard-surface induced protein 1 gene), which encodes
      a ubiquitin-conjugating enzyme. RNA blots clearly showed that it is induced by
      hard-surface contact and that ethylene treatment enhanced this induction. The
      predicted open reading frame (ubc1Cg) would encode a 16.2-kDa ubiquitin
      conjugating enzyme, which shows 82% identity to the Saccharomyces cerevisiae UBC4
      UBC5 E2 enzyme, comprising a major part of total ubiquitin-conjugating activity
      in stressed yeast cells. UBC1Cg can complement the proteolysis deficiency of the
      S. cerevisiae ubc4 ubc5 mutant, indicating that ubiquitin-dependent protein
      degradation is involved in conidial germination and appressorial differentiation.

PMID- 9658003
TI  - Circadian rhythm of nitrogenase gene expression in the diazotrophic filamentous
      nonheterocystous cyanobacterium Trichodesmium sp. strain IMS 101.
AB  - Recent studies suggested that the daily cycle of nitrogen fixation activity in
      the marine filamentous nonheterocystous cyanobacterium Trichodesmium sp. is
      controlled by a circadian rhythm. In this study, we evaluated the rhythm of
      nitrogen fixation in Trichodesmium sp. strain IMS 101 by using the three criteria
      for an endogenous rhythm. Nitrogenase transcript abundance oscillated with a
      period of approximately 24 h, and the cycle was maintained even under constant
      light conditions. The cyclic pattern of transcript abundance was maintained when
      the culture was grown at 24 and 28.5 degrees C, although the period was slightly
      longer (26 h) at the higher temperature. The cycle of gene expression could be
      entrained with light-dark cues. Results of inhibitor experiments indicated that
      transcript abundance was regulated primarily by transcription initiation, rather
      than by degradation. The circadian rhythm, the first conclusively demonstrated
      endogenous rhythm in a filamentous cyanobacterium, was also reflected in
      nitrogenase MoFe protein abundance and patterns of Fe protein posttranslational
      modification-demodification.

PMID- 9658004
TI  - Copper-binding compounds from Methylosinus trichosporium OB3b.
AB  - Two copper-binding compounds/cofactors (CBCs) were isolated from the spent media
      of both the wild type and a constitutive soluble methane monooxygenase (sMMOC)
      mutant, PP319 (P. A. Phelps et al., Appl. Environ. Microbiol. 58:3701-3708,
      1992), of Methylosinus trichosporium OB3b. Both CBCs are small polypeptides with
      molecular masses of 1,218 and 779 Da for CBC-L1 and CBC-L2, respectively. The
      amino acid sequence of CBC-L1 is S?MYPGS?M, and that of CBC-L2 is SPMP?S. Copper
      free CBCs showed absorption maxima at 204, 275, 333, and 356 with shoulders at
      222 and 400 nm. Copper-containing CBCs showed a broad absorption maximum at 245
      nm. The low-temperature electron paramagnetic resonance (EPR) spectra of copper
      containing CBC-L1 showed the presence of a copper center with an EPR splitting
      constant between those of type 1 and type 2 copper centers (g = 2.087, g = 2.42
      G, A = 128 G). The EPR spectrum of CBC-L2 was more complex and showed two
      spectrally distinct copper centers. One signal can be attributed to a type 2 Cu2+
      center (g = 2.073, g = 2.324 G, A = 144 G) which could be saturated at higher
      powers, while the second shows a broad, nearly isotropic signal near g = 2.063.
      In wild-type strains, the concentrations of CBCs in the spent media were highest
      in cells expressing the pMMO and stressed for copper. In contrast to wild-type
      strains, high concentrations of CBCs were observed in the extracellular fraction
      of the sMMOC mutants PP319 and PP359 regardless of the copper concentration in
      the culture medium.

PMID- 9658005
TI  - Lack of S-adenosylmethionine results in a cell division defect in Escherichia
      coli.
AB  - The enzyme S-adenosylmethionine (SAM) synthetase, the Escherichia coli metK gene
      product, produces SAM, the cell's major methyl donor. We show here that SAM
      synthetase activity is induced by leucine and repressed by Lrp, the leucine
      responsive regulatory protein. When SAM synthetase activity falls below a certain
      critical threshold, the cells produce long filaments with regularly distributed
      nucleoids. Expression of a plasmid-carried metK gene prevents filamentation and
      restores normal growth to the metK mutant. This indicates that lack of SAM
      results in a division defect.

PMID- 9658006
TI  - Differential regulation of Rhizobium etli rpoN2 gene expression during symbiosis
      and free-living growth.
AB  - The Rhizobium etli rpoN1 gene, encoding the alternative sigma factor sigma54
      (RpoN), was recently characterized and shown to be involved in the assimilation
      of several nitrogen and carbon sources during free-living aerobic growth (J.
      Michiels, T. Van Soom, I. D'hooghe, B. Dombrecht, T. Benhassine, P. de Wilde, and
      J. Vanderleyden, J. Bacteriol. 180:1729-1740, 1998). We identified a second rpoN
      gene copy in R. etli, rpoN2, encoding a 54.0-kDa protein which displays 59% amino
      acid identity with the R. etli RpoN1 protein. The rpoN2 gene is cotranscribed
      with a short open reading frame, orf180, which codes for a protein with a size of
      20.1 kDa that is homologous to several prokaryotic and eukaryotic proteins of
      similar size. In contrast to the R. etli rpoN1 mutant strain, inactivation of the
      rpoN2 gene did not produce any phenotypic defects during free-living growth.
      However, symbiotic nitrogen fixation was reduced by approximately 90% in the
      rpoN2 mutant, whereas wild-type levels of nitrogen fixation were observed in the
      rpoN1 mutant strain. Nitrogen fixation was completely abolished in the rpoN1
      rpoN2 double mutant. Expression of rpoN1 was negatively autoregulated during
      aerobic growth and was reduced during microaerobiosis and symbiosis. In contrast,
      rpoN2-gusA and orf180-gusA fusions were not expressed aerobically but were
      strongly induced at low oxygen tensions or in bacteroids. Expression of rpoN2 and
      orf180 was abolished in R. etli rpoN1 rpoN2 and nifA mutants under all conditions
      tested. Under free-living microaerobic conditions, transcription of rpoN2 and
      orf180 required the RpoN1 protein. In symbiosis, expression of rpoN2 and orf180
      occurred independently of the rpoN1 gene, suggesting the existence of an
      alternative symbiosis-specific mechanism of transcription activation.

PMID- 9658007
TI  - RpoS (sigma-S) controls expression of rsmA, a global regulator of secondary
      metabolites, harpin, and extracellular proteins in Erwinia carotovora.
AB  - RpoS (sigma-S or sigma-38) controls a large array of genes that are expressed
      during stationary phase and under various stress conditions in Escherichia coli
      and other bacteria. We document here that plant pathogenic and epiphytic Erwinia
      species, such as E. amylovora; E. carotovora subsp. atroseptica, betavasculorum,
      and carotovora; E. chrysanthemi; E. herbicola; E. rhapontici; and E. stewartii,
      possess rpoS genes and produce the alternate sigma factor. We show that rpoS
      transcription in E. carotovora subsp. carotovora is driven from a major promoter
      which resides within the nlpD gene located upstream of rpoS as in E. coli. RpoS-
      E. carotovora subsp. carotovoa strain AC5061, constructed by marker exchange, is
      more sensitive to hydrogen peroxide, carbon starvation, and acidic pH than its
      RpoS+ parent strain, AC5006. The basal levels of extracellular pectate lyase,
      polygalacturonase, and cellulase as well as those of transcripts of E. carotovora
      subsp. carotovora hrpN (hrpNEcc), the gene for the elicitor of the hypersensitive
      reaction, are higher in the RpoS- strain than in the RpoS+ parent. Likewise,
      compared to AC5006, AC5061 causes more extensive maceration of celery petioles.
      Our findings with the RpoS- mutant and strains carrying multiple copies rpoS+ DNA
      reveal that rpoS positively controls rsmA expression. We also present evidence
      that supports the hypothesis that the RpoS effect on extracellular enzyme levels,
      hrpNEcc expression, and virulence manifests itself by the modulation of rsmA
      expression.

PMID- 9658008
TI  - Molecular characterization and postsplicing fate of three introns within the
      single rRNA operon of the hyperthermophilic archaeon Aeropyrum pernix K1.
AB  - The single rRNA operon (arnS-arnL) of the hyperthermophilic archaeon Aeropyrum
      pernix K1 was sequenced. The DNA sequence data and detailed RNA analyses
      disclosed an unusual feature: the presence of three introns at hitherto
      undescribed insertion positions within the rRNA genes. The 699-nucleotide (nt)
      intron Ialpha was located at position 908 (Escherichia coli numbering [H. F.
      Noller, Annu. Rev. Biochem. 53:119-162, 1984]) of the 16S rRNA, while the 202-nt
      intron Ibeta and 575-nt intron Igamma were located at positions 1085 and 1927 (E.
      coli numbering), respectively, of the 23S rRNA. They were located within highly
      conserved sites which have been implicated as crucial for rRNA function in E.
      coli. All three introns were remarkably AT rich (41.5 to 43.1 mol% G+C) compared
      with the mature rRNAs (67.7 and 69.2 mol% G+C for 16S and 23S rRNAs,
      respectively). No obvious primary sequence similarities were detected among them.
      After splicing from rRNA transcripts in vivo, a large quantity of intronic RNAs
      were stably retained in the linear monomeric form, whereas a trace of
      topoisomeric RNA molecules also appeared, as characterized by their behavior in
      two-dimensional gel electrophoresis. Secondary structural models of the Ialpha-,
      Ibeta-, and Igamma-containing rRNA precursors agree with the bulge-helix-bulge
      motif. Two of the introns, Ialpha and Igamma, contained open reading frames whose
      protein translation exhibited no overall similarity with proteins reported so
      far. However, both share a LAGLI-DADG motif characteristic of homing
      endonucleases.

PMID- 9658009
TI  - Evidence of two oxidative reaction steps initiating anaerobic degradation of
      resorcinol (1,3-dihydroxybenzene) by the denitrifying bacterium Azoarcus
      anaerobius.
AB  - The denitrifying bacterium Azoarcus anaerobius LuFRes1 grows anaerobically with
      resorcinol (1,3-dihydroxybenzene) as the sole source of carbon and energy. The
      anaerobic degradation of this compound was investigated in cell extracts.
      Resorcinol reductase, the key enzyme for resorcinol catabolism in fermenting
      bacteria, was not present in this organism. Instead, resorcinol was hydroxylated
      to hydroxyhydroquinone (HHQ; 1,2,4-trihydroxybenzene) with nitrate or K3Fe(CN)6
      as the electron acceptor. HHQ was further oxidized with nitrate to 2-hydroxy-1,4
      benzoquinone as identified by high-pressure liquid chromatography, UV/visible
      light spectroscopy, and mass spectroscopy. Average specific activities were 60 mU
      mg of protein-1 for resorcinol hydroxylation and 150 mU mg of protein-1 for HHQ
      dehydrogenation. Both activities were found nearly exclusively in the membrane
      fraction and were only barely detectable in extracts of cells grown with
      benzoate, indicating that both reactions were specific for resorcinol
      degradation. These findings suggest a new strategy of anaerobic degradation of
      aromatic compounds involving oxidative steps for destabilization of the aromatic
      ring, different from the reductive dearomatization mechanisms described so far.

PMID- 9658010
TI  - General stress transcription factor sigmaB and its role in acid tolerance and
      virulence of Listeria monocytogenes.
AB  - The gene encoding the general stress transcription factor sigmaB in the gram
      positive bacterium Listeria monocytogenes was isolated with degenerate PCR
      primers followed by inverse PCR amplification. Evidence for gene identification
      includes the following: (i) phylogenetic analyses of reported amino acid
      sequences for sigmaB and the closely related sigmaF proteins grouped L.
      monocytogenes sigmaB in the same cluster with the sigmaB proteins from Bacillus
      subtilis and Staphylococcus aureus, (ii) the gene order in the 2, 668-bp portion
      of the L. monocytogenes sigB operon is rsbU-rsbV-rsbW-sigB-rsbX and is therefore
      identical to the order of the last five genes of the B. subtilis sigB operon, and
      (iii) an L. monocytogenes sigmaB mutant had reduced resistance to acid stress in
      comparison with its isogenic parent strain. The sigB mutant was further
      characterized in mouse models of listeriosis by determining recovery rates of the
      wild-type and mutant strains from livers and spleens following intragastric or
      intraperitoneal infection. Our results suggest that sigmaB-directed genes do not
      appear to be essential for the spread of L. monocytogenes to mouse liver or
      spleen at 2 and 4 days following intragastric or intraperitoneal infection.

PMID- 9658011
TI  - Tca1, the retrotransposon-like element of Candida albicans, is a degenerate and
      inactive element.
AB  - Candida albicans is an asexual fungus and as such must rely on mechanisms other
      than sexual recombination to generate genetic diversity. Retrotransposons are
      ubiquitous genetic elements known to generate multiple types of genomic
      alterations. We have further investigated the nature of the retrotransposon-like
      element Tca1 in C. albicans. Tca1 is present at two loci in strain SC5314. Both
      loci have now been cloned, and one element was sequenced in its entirety. This
      element was flanked by alpha elements, or long terminal repeats (LTRs), and
      contained an intervening region of 5,614 bp. The intervening region was highly
      degenerate and contained no extended open reading frames, indicating that Tca1 is
      not a functional element. Partial sequence determination demonstrated that the
      elements from the two loci were nearly identical. Genetic manipulation of the
      elements showed that both loci were heterozygous for Tca1, that both were
      transcriptionally active, and that deletion of both had no effect on growth rate
      or germ tube formation. Thus, it is unclear why this nonfunctional, highly
      degenerate element has been maintained in many clinical isolates.

PMID- 9658012
TI  - ftsE(Ts) affects translocation of K+-pump proteins into the cytoplasmic membrane
      of Escherichia coli.
AB  - The ftsE(Ts) mutation of Escherichia coli causes defects in cell division and
      cell growth. We expressed alkaline phosphatase (PhoA) fusion proteins of KdpA,
      Kup, and TrkH, all of which proved functional in vivo as K+ ion pumps, in the
      mutant cells. During growth at 41 degrees C, these proteins were progressively
      lost from the membrane fraction. The reduction in the abundance of these proteins
      inversely correlated with cell growth, but the preformed proteins in the membrane
      were stable at 41 degrees C, indicating that the molecules synthesized at the
      permissive temperature were diluted in a growth-dependent manner at a high
      temperature. Pulse-chase experiments showed that KdpA-PhoA was synthesized, but
      the synthesized protein did not translocate into the membrane of the ftsE(Ts)
      cells at 41 degrees C and degraded very rapidly. The loss of KdpA-PhoA from the
      membrane fractions of ftsE(Ts) cells was suppressed by a multicopy plasmid
      carrying the ftsE+ gene. While cell growth stopped when the abundance of these
      proteins decreased 15-fold, the addition of a high concentration of K+ ions
      specifically alleviated the growth defect of ftsE(Ts) cells but not cell
      division, and the cells elongated more than 100-fold. We conclude that one of the
      causes of growth cessation in the ftsE(Ts) mutants is a defect in the
      translocation of K+-pump proteins into the cytoplasmic membrane.

PMID- 9658013
TI  - Isolation and characterization of Bacillus subtilis sigB operon mutations that
      suppress the loss of the negative regulator RsbX.
AB  - sigmaB, a transcription factor that controls the Bacillus subtilis general stress
      response regulon, is activated by either a drop in intracellular ATP or exposure
      to environmental stress. RsbX, one of seven sigmaB regulators (Rsb proteins)
      whose genes are cotranscribed with sigmaB, is a negative regulator in the stress
      dependent activation pathway. To better define the interactions that take place
      among the Rsb proteins, we analyzed sigB operon mutations which suppress the high
      level sigmaB activity that normally accompanies the loss of RsbX. Each of these
      mutations was in one of three genes (rsbT, -U, and -V) which encode positive
      regulators of sigmaB, and they all defined amino acid changes which either
      compromised the activities of the mutant Rsbs or affected their ability to
      accumulate. sigmaB activity remained inducible by ethanol in several of the RsbX-
      suppressor strains. This finding supports the notion that RsbX is not needed as
      the target for sigmaB activation by at least some stresses. sigmaB activity in
      several RsbX- strains with suppressor mutations in rsbT or -U was high during
      growth and underwent a continued, rather than a transient, increase following
      stress. Thus, RsbX is likely responsible for maintaining low sigmaB activity
      during balanced growth and for reestablishing sigmaB activity at prestress levels
      following induction. Although RsbX likely participates in limiting the sigmaB
      induction response, a second mechanism for curtailing unrestricted sigmaB
      activation was suggested by the sigmaB induction profile in two suppressor
      strains with mutations in rsbV. sigmaB activity in these mutants was stress
      inducible but transient, even in the absence of RsbX.

PMID- 9658014
TI  - Low ubiquinone content in Escherichia coli causes thiol hypersensitivity.
AB  - Thiol hypersensitivity in a mutant of Escherichia coli (IS16) was reversed by
      complementation with a plasmid that carried the ubiX gene. The mutant had low
      ubiquinone content. Complementation elevated the ubiquinone level and eliminated
      thiol hypersensitivity. Analysis of chromosomal ubiX genes indicated that both
      parent and mutant strains were ubiX mutants. The low ubiquinone content of IS16
      was possibly caused by a ubiD ubiX genotype. A ubiA mutant also exhibited thiol
      hypersensitivity. Neither IS16 nor the ubiA mutant strain could produce alkaline
      phosphatase (in contrast to their parent strains) after 2 h of induction, thus
      showing Dsb- phenotypes. The phenomena of thiol hypersensitivity and low
      ubiquinone content may be linked by their connections to the periplasmic
      disulfide bond redox machinery.

PMID- 9658015
TI  - A periplasmic and extracellular c-type cytochrome of Geobacter sulfurreducens
      acts as a ferric iron reductase and as an electron carrier to other acceptors or
      to partner bacteria.
AB  - An extracellular electron carrier excreted into the growth medium by cells of
      Geobacter sulfurreducens was identified as a c-type cytochrome. The cytochrome
      was found to be distributed in about equal amounts in the membrane fraction, the
      periplasmic space, and the surrounding medium during all phases of growth with
      acetate plus fumarate. It was isolated from periplasmic preparations and purified
      to homogeneity by cation-exchange chromatography, gel filtration, and hydrophobic
      interaction chromatography. The electrophoretically homogeneous cytochrome had a
      molecular mass of 9.57 +/- 0.02 kDa and exhibited in its reduced state absorption
      maxima at wavelengths of 552, 522, and 419 nm. The midpoint redox potential
      determined by redox titration was -0.167 V. With respect to molecular mass, redox
      properties, and molecular features, this cytochrome exhibited its highest
      similarity to the cytochromes c of Desulfovibrio salexigens and Desulfuromonas
      acetoxidans. The G. sulfurreducens cytochrome c reduced ferrihydrite (Fe(OH)3),
      Fe(III) nitrilotriacetic acid, Fe(III) citrate, and manganese dioxide at high
      rates. Elemental sulfur, anthraquinone disulfonate, and humic acids were reduced
      more slowly. G. sulfurreducens reduced the cytochrome with acetate as an electron
      donor and oxidized it with fumarate. Wolinella succinogenes was able to reduce
      externally provided cytochrome c of G. sulfurreducens with molecular hydrogen or
      formate as an electron donor and oxidized it with fumarate or nitrate as an
      electron acceptor. A coculture could be established in which G. sulfurreducens
      reduced the cytochrome with acetate, and the reduced cytochrome was reoxidized by
      W. succinogenes in the presence of nitrate. We conclude that this cytochrome can
      act as iron(III) reductase for electron transfer to insoluble iron hydroxides or
      to sulfur, manganese dioxide, or other oxidized compounds, and it can transfer
      electrons to partner bacteria.

PMID- 9658016
TI  - Isolation and characterization of toluene-sensitive mutants from the toluene
      resistant bacterium Pseudomonas putida GM73.
AB  - To understand the mechanism underlying toluene resistance of a toluene-tolerant
      bacterium, Pseudomonas putida GM73, we carried out Tn5 mutagenesis and isolated
      eight toluene-sensitive mutants. None of the mutants grew in the presence of 20%
      (vol/vol) toluene in growth medium but exhibited differential sensitivity to
      toluene. When wild-type cells were treated with toluene (1% [vol/vol]) for 5 min,
      about 2% of the cells could form colonies. In the mutants Ttg1, Ttg2, Ttg3, and
      Ttg8, the same treatment killed more than 99.9999% of cells (survival rate, <10(
      6)). In Ttg4, Ttg5, Ttg6, and Ttg7, about 0.02% of cells formed colonies. We
      cloned the Tn5-inserted genes, and the DNA sequence flanking Tn5 was determined.
      From comparison with a sequence database, putative protein products encoded by
      ttg genes were identified as follows. Ttg1 and Ttg2 are ATP binding cassette
      (ABC) transporter homologs; Ttg3 is a periplasmic linker protein of a toluene
      efflux pump; both Ttg4 and Ttg7 are pyruvate dehydrogenase; Ttg5 is a
      dihydrolipoamide acetyltransferase; and Ttg7 is the negative regulator of the
      phosphate regulon. The sequences deduced from ttg8 did not show a significant
      similarity to any DNA or proteins in sequence databases. Characterization of
      these mutants and identification of mutant genes suggested that active efflux
      mechanism and efficient repair of damaged membranes were important in toluene
      resistance.

PMID- 9658017
TI  - Molecular cloning and nucleotide sequence of the superoxide dismutase gene and
      characterization of its product from Bacillus subtilis.
AB  - Bacillus subtilis was found to possess one detectable superoxide dismutase (Sod)
      in both vegetative cells and spores. The Sod activity in vegetative cells was
      maximal at stationary phase. Manganese was necessary to sustain Sod activity at
      stationary phase, but paraquat, a superoxide generator, did not induce the
      expression of Sod. The specific activity of purified Sod was approximately 2, 600
      U/mg of protein, and the enzyme was a homodimer protein with a molecular mass of
      approximately 25,000 per monomer. The gene encoding Sod, designated sodA, was
      cloned by the combination of several PCR methods and the Southern hybridization
      method. DNA sequence analysis revealed the presence of one open reading frame
      consisting of 606 bp. Several putative promoter sites were located in the
      upstream region of sodA. The deduced amino acid sequence showed high homology
      with other bacterial manganese Sods. Conserved regions in bacterial manganese Sod
      could also be seen. The phenotype of double mutant Escherichia coli sodA sodB,
      which could not grow in minimal medium without supplemental amino acids, was
      complemented by the expression of B. subtilis sodA.

PMID- 9658018
TI  - Sequence analysis of the GntII (subsidiary) system for gluconate metabolism
      reveals a novel pathway for L-idonic acid catabolism in Escherichia coli.
AB  - The presence of two systems in Escherichia coli for gluconate transport and
      phosphorylation is puzzling. The main system, GntI, is well characterized, while
      the subsidiary system, GntII, is poorly understood. Genomic sequence analysis of
      the region known to contain genes of the GntII system led to a hypothesis which
      was tested biochemically and confirmed: the GntII system encodes a pathway for
      catabolism of L-idonic acid in which D-gluconate is an intermediate. The genes
      have been named accordingly: the idnK gene, encoding a thermosensitive gluconate
      kinase, is monocistronic and transcribed divergently from the idnD-idnO-idnT-idnR
      operon, which encodes L-idonate 5-dehydrogenase, 5-keto-D-gluconate 5-reductase,
      an L-idonate transporter, and an L-idonate regulatory protein, respectively. The
      metabolic sequence is as follows: IdnT allows uptake of L-idonate; IdnD catalyzes
      a reversible oxidation of L-idonate to form 5-ketogluconate; IdnO catalyzes a
      reversible reduction of 5-ketogluconate to form D-gluconate; IdnK catalyzes an
      ATP-dependent phosphorylation of D-gluconate to form 6-phosphogluconate, which is
      metabolized further via the Entner-Doudoroff pathway; and IdnR appears to act as
      a positive regulator of the IdnR regulon, with L-idonate or 5-ketogluconate
      serving as the true inducer of the pathway. The L-idonate 5-dehydrogenase and 5
      keto-D-gluconate 5-reductase reactions were characterized both chemically and
      biochemically by using crude cell extracts, and it was firmly established that
      these two enzymes allow for the redox-coupled interconversion of L-idonate and D
      gluconate via the intermediate 5-ketogluconate. E. coli K-12 strains are able to
      utilize L-idonate as the sole carbon and energy source, and as predicted, the
      ability of idnD, idnK, idnR, and edd mutants to grow on L-idonate is altered.

PMID- 9658019
TI  - The central, surface-exposed region of the flagellar hook protein FlgE of
      Campylobacter jejuni shows hypervariability among strains.
AB  - In a previous study, we observed that monoclonal antibodies raised against the
      hook protein FlgE of Campylobacter jejuni LIO 36, isolate 5226, bound exclusively
      to this strain. The aim of this study was to elucidate the molecular basis for
      these binding specificities. The hook protein-encoding gene flgE of C. jejuni was
      cloned in Escherichia coli and sequenced. The flgE genes of four additional C.
      jejuni strains were amplified by PCR and also sequenced. Comparison of the
      deduced amino acid sequences revealed a high degree of variability in the central
      parts of the FlgE proteins among the strains, including variable and
      hypervariable domains. These findings may indicate a selective pressure of C.
      jejuni hosts, forcing the bacteria to generate variations in surface-exposed
      antigenic determinants.

PMID- 9658020
TI  - Temperature regulation of heat-labile enterotoxin (LT) synthesis in Escherichia
      coli is mediated by an interaction of H-NS protein with the LT A-subunit DNA.
AB  - Protein and mRNA levels of heat-labile enterotoxin (LT) of Escherichia coli are
      highest at 37 degrees C, and they decrease gradually as temperature is decreased.
      This temperature effect is eliminated in an Hns- mutant. Deletion of portions of
      DNA coding for the LT A subunit also results in an increase in LT expression at
      low temperatures, suggesting that the H-NS protein causes inhibition of
      transcription at low temperatures by interacting with the LT A-subunit DNA. The
      region that interacts with H-NS is referred to as the downstream regulatory
      element (DRE). Plasmids in an hns strain from which the DRE has been deleted
      still produce elevated levels of LT at 18 degrees C, suggesting that intact DRE
      is not required for transcription from the LT promoter.

PMID- 9658021
TI  - Diversity of cytochrome bc complexes: example of the Rieske protein in green
      sulfur bacteria.
AB  - The Rieske 2Fe2S cluster of Chlorobium limicola forma thiosulfatophilum strain
      tassajara was studied by electron paramagnetic resonance spectroscopy. Two
      distinct orientations of its g tensor were observed in oriented samples
      corresponding to differing conformations of the protein. Only one of the two
      conformations persisted after treatment with 2,5-dibromo-3-methyl-6-isopropyl-p
      benzoquinone. A redox midpoint potential (Em) of +160 mV in the pH range of 6 to
      7.7 and a decreasing Em (-60 to -80 mV/pH unit) above pH 7.7 were found. The
      implications of the existence of differing conformational states of the Rieske
      protein, as well as of the shape of its Em-versus-pH curve, in green sulfur
      bacteria are discussed.

PMID- 9658022
TI  - Opposing roles of the Staphylococcus aureus virulence regulators, Agr and Sar, in
      Triton X-100- and penicillin-induced autolysis.
AB  - The regulation of murein hydrolases is a critical aspect of peptidoglycan growth
      and metabolism. In the present study, we demonstrate that mutations within the
      Staphylococcus aureus virulence factor regulatory genes, agr and sar, affect
      autolysis, resulting in decreased and increased autolysis rates, respectively.
      Zymographic analyses of these mutant strains suggest that agr and sar exert their
      effects on autolysis, in part, by modulating murein hydrolase expression and/or
      activity.

PMID- 9658023
TI  - A minisatellite sequence within the propeptide region of the vacuolar
      carboxypeptidase Y gene of Schizosaccharomyces pombe.
AB  - We describe the presence of a minisatellite sequence that displays length
      polymorphisms in the fission yeast Schizosaccharomyces pombe. The minisatellite
      sequence was found to reside within the propeptide region of the vacuolar
      carboxypeptidase Y gene. The minisatellite sequence, which was found only at a
      single locus, was mitotically stable and displayed length polymorphisms between
      the two varieties of S. pombe (S. pombe var. pombe and S. pombe var.
      malidevorans). The minisatellite sequence, however, appeared to be species
      specific and was absent in other members of the Schizosaccharomyces genus. This
      report constitutes the first experimental demonstration of the presence of such
      sequences in yeasts.

PMID- 9658024
TI  - General stress transcription factor sigmaB and sporulation transcription factor
      sigmaH each contribute to survival of Bacillus subtilis under extreme growth
      conditions.
AB  - The general stress response of the bacterium Bacillus subtilis is controlled by
      the sigmaB transcription factor. Here we show that loss of sigmaB reduces
      stationary-phase viability 10-fold in either alkaline or acidic media and reduces
      cell yield in media containing ethanol. We further show that loss of the
      developmental transcription factor sigmaH also has a marked effect on stationary
      phase viability under these conditions and that this effect is independent from
      the simple loss of sporulation ability.

PMID- 9658025
TI  - Predictive reward signal of dopamine neurons.
AB  - The effects of lesions, receptor blocking, electrical self-stimulation, and drugs
      of abuse suggest that midbrain dopamine systems are involved in processing reward
      information and learning approach behavior. Most dopamine neurons show phasic
      activations after primary liquid and food rewards and conditioned, reward
      predicting visual and auditory stimuli. They show biphasic, activation-depression
      responses after stimuli that resemble reward-predicting stimuli or are novel or
      particularly salient. However, only few phasic activations follow aversive
      stimuli. Thus dopamine neurons label environmental stimuli with appetitive value,
      predict and detect rewards and signal alerting and motivating events. By failing
      to discriminate between different rewards, dopamine neurons appear to emit an
      alerting message about the surprising presence or absence of rewards. All
      responses to rewards and reward-predicting stimuli depend on event
      predictability. Dopamine neurons are activated by rewarding events that are
      better than predicted, remain uninfluenced by events that are as good as
      predicted, and are depressed by events that are worse than predicted. By
      signaling rewards according to a prediction error, dopamine responses have the
      formal characteristics of a teaching signal postulated by reinforcement learning
      theories. Dopamine responses transfer during learning from primary rewards to
      reward-predicting stimuli. This may contribute to neuronal mechanisms underlying
      the retrograde action of rewards, one of the main puzzles in reinforcement
      learning. The impulse response releases a short pulse of dopamine onto many
      dendrites, thus broadcasting a rather global reinforcement signal to postsynaptic
      neurons. This signal may improve approach behavior by providing advance reward
      information before the behavior occurs, and may contribute to learning by
      modifying synaptic transmission. The dopamine reward signal is supplemented by
      activity in neurons in striatum, frontal cortex, and amygdala, which process
      specific reward information but do not emit a global reward prediction error
      signal. A cooperation between the different reward signals may assure the use of
      specific rewards for selectively reinforcing behaviors. Among the other
      projection systems, noradrenaline neurons predominantly serve attentional
      mechanisms and nucleus basalis neurons code rewards heterogeneously. Cerebellar
      climbing fibers signal errors in motor performance or errors in the prediction of
      aversive events to cerebellar Purkinje cells. Most deficits following dopamine
      depleting lesions are not easily explained by a defective reward signal but may
      reflect the absence of a general enabling function of tonic levels of
      extracellular dopamine. Thus dopamine systems may have two functions, the phasic
      transmission of reward information and the tonic enabling of postsynaptic
      neurons.

PMID- 9658026
TI  - Neuronal responses related to smooth pursuit eye movements in the periarcuate
      cortical area of monkeys.
AB  - To examine how the periarcuate area is involved in the control of smooth pursuit
      eye movements, we recorded 177 single neurons while monkeys pursued a moving
      target in the dark. The majority (52%, 92/177) of task-related neurons responded
      to pursuit but had little or no response to saccades. Histological
      reconstructions showed that these neurons were located mainly in the posterior
      bank of the arcuate sulcus near the sulcal spur. Twenty-seven percent (48/177)
      changed their activity at the onset of saccades. Of these, 36 (75%) showed
      presaccadic burst activity with strong preference for contraversive saccades.
      Eighteen (10%, 18/177) were classified as eye-position-related neurons, and 11%
      (19/177) were related to other aspects of the stimuli or response. Among the 92
      neurons that responded to pursuit, 85 (92%) were strongly directional with
      uniformly distributed preferred directions. Further analyses were performed in
      these directionally sensitive pursuit-related neurons. For 59 neurons that showed
      distinct changes in activity around the initiation of pursuit, the median latency
      from target motion was 96 ms and that preceding pursuit was -12 ms, indicating
      that these neuron can influence the initiation of pursuit. We tested some neurons
      by briefly extinguishing the tracking target (n = 39) or controlling its movement
      with the eye position signal (n = 24). The distribution of the change in pursuit
      related activity was similar to previous data for the dorsomedial part of the
      medial superior temporal neurons (, indicating that pursuit-related neurons in
      the periarcuate area also carry extraretinal signals. For 22 neurons, we examined
      the responses when the animals reversed pursuit direction to distinguish the
      effects of eye acceleration in the preferred direction from oppositely directed
      eye velocity. Almost all neurons discharged before eye velocity reached zero,
      however, only nine neurons discharged before the eyes were accelerated in the
      preferred direction. The delay in neuronal responses relative to the onset of eye
      acceleration in these trials might be caused by suppression from oppositely
      directed pursuit velocity. The results suggest that the periarcuate neurons do
      not participate in the earliest stage of eye acceleration during the change in
      pursuit direction, although most of them may participate in the early stages of
      pursuit initiation in the ordinary step-ramp pursuit trials. Some neurons changed
      their activity when the animals fixated a stationary target, and this activity
      could be distinguished easily from the strong pursuit-related responses. Our
      results suggest that the periarcuate pursuit area carries extraretinal signals
      and affects the premotor circuitry for smooth pursuit.

PMID- 9658027
TI  - Modulation of the inspiratory-related activity of hypoglossal premotor neurons
      during ingestion and rejection in the decerebrate cat.
AB  - Single-unit activities of the bulbar reticular inspiratory neurons directly
      projecting to hypoglossal motoneurons were studied during fictive ingestion
      (e.g., swallowing) and rejection elicited by repetitive stimulation of the
      superior laryngeal nerve and by application of water to the pharynx in
      immobilized decerebrated cats. The single-unit activity was recorded during 113
      episodes of fictive ingestion from 25 inspiratory neurons directly projecting to
      hypoglossal motoneurons (single projection neurons) and 7 inspiratory neurons
      directly projecting to both hypoglossal and phrenic motoneurons (dual projection
      neurons) in the regions ventrolateral to the nucleus tractus solitarii and
      dorsomedial to the nucleus ambiguus. All of single projection neurons ceased
      inspiratory-related rhythmical discharges coincidentally with the onset of
      repetitive stimulation of the superior laryngeal nerve. The majority of them
      (19/25, 76%, type A) showed a spike burst during ingestion, whereas the minority
      (6/25, 24%, type B) kept silent until the end of repetitive stimulation of the
      superior laryngeal nerve. During fictive ingestion elicited by application of
      water to the pharynx, the type-A neurons showed a spike burst activity, whereas
      the type-B neurons kept silent. All dual projection neurons (7/7, 100%, type C)
      ceased inspiratory-related rhythmical discharges at the onset of repetitive
      stimulation of the superior laryngeal nerve and showed no activity during fictive
      ingestion. Likewise, the type-C neurons kept silent during fictive ingestion
      elicited by application of water to the pharynx. A spike burst was induced during
      33 episodes of fictive rejection in all of 5 tested type-A, 3 tested type-B, and
      6 tested type-C neurons. It is concluded that the premotor neurons involved in
      the respiratory-related rhythmical activity of hypoglossal motoneurons is
      responsible for switching from respiration to ingestion and rejection.

PMID- 9658028
TI  - Primate red nucleus discharge encodes the dynamics of limb muscle activity.
AB  - We studied the dynamical relationship between magnocellular red nucleus (RNm)
      discharge and electromyographic (EMG) activity of 10-15 limb muscles in two
      monkeys during voluntary limb movement. Recordings were made from 158 neurons
      during two different kinds of limb movement tasks. One was a tracking task in
      which the subjects were required to acquire targets displayed on an oscilloscope
      by rotating one of six different single degree of freedom manipulanda. During
      this task, we recorded the angular position of the manipulandum. The monkeys also
      were trained in several free-form food-retrieval tasks that were much less
      constrained mechanically. There was generally significantly greater neuronal
      discharge during the free-form tasks than during the tracking task. During both
      types of tasks, cross-correlation and impulse response functions calculated
      between RNm and EMG were predominantly pulse-shaped, indicating that the dynamics
      of the RNm discharge were very similar to those of the muscle activity. There was
      no evidence during either task for a substantial dynamical transformation (e.g.,
      integration) between the two signals as had been previously suggested. In only
      15% of the cases, did these correlations have step or pulse-step dynamics. There
      was a relatively broad, unimodal distribution of lag times between RNm and EMG,
      based on the time of occurrence of the peak correlation. During tracking, the
      mode of this distribution was approximately 50 ms, with 80% of the lags falling
      between -100 and 200 ms. During the free-form task, the mode was between 0 and 20
      ms, with 65% of the lags between -100 and 200 ms. A positive lag indicates that
      RNm discharge preceded EMG. The shape and timing of both the cross-correlation
      and the impulse response functions were consistent with a model in which many RNm
      neurons contribute mutually correlated signals which are simply summed within the
      spinal cord to produce a muscle activation signal.

PMID- 9658029
TI  - GABAergic and glycinergic inhibition sharpens tuning for frequency modulations in
      the inferior colliculus of the big brown bat.
AB  - Discrimination of amplitude and frequency modulated sounds is an important task
      of auditory processing. Experiments have shown that tuning of neurons to
      sinusoidally frequency- and amplitude-modulated (SFM and SAM, respectively)
      sounds becomes successively narrower going from lower to higher auditory brain
      stem nuclei. In the inferior colliculus (IC), many neurons are sharply tuned to
      the modulation frequency of SFM sounds. The purpose of this study was to
      determine whether GABAergic or glycinergic inhibition is involved in shaping the
      tuning for the modulation frequency of SFM sounds in IC neurons of the big brown
      bat (Eptesicus fuscus). We recorded the response of 56 single units in the
      central nucleus of the IC to SFM stimuli before and during the application of the
      gamma-aminobutyric acid-A (GABAA) receptor antagonist bicuculline or the glycine
      receptor antagonist strychnine. To evaluate tuning to the modulation frequency,
      the normalized spike count (normalized according to the maximal response for each
      condition tested) was plotted versus the modulation frequency and the upper and
      lower 50% cutoff points were determined. Bicuculline increased the upper cutoff
      in 46% of the neurons by >/=25%. The lower cutoff decreased in 48% of the neurons
      tested. In some neurons (approximately 30%), a sharpening of the tuning by
      bicuculline was observed. Strychnine induced an increase of the upper cutoff in
      almost half of the neurons. Compared with bicuculline these changes were smaller.
      The lower cutoff decreased in 50% of the neurons with strychnine. The
      synchronization coefficient (SC) was calculated and compared for three modulation
      frequencies (50, 100, and 200 Hz) between predrug and drug condition. For all
      neurons, synchronization decreased (n = 36) or did not change (n = 26) during
      drug application. This was mainly an effect of the prolonged discharge in
      response to each cycle. Under predrug conditions, many neurons exhibited
      selectivity to the direction of the FM, hence they only responded once to each
      cycle. In a minority of neurons, direction selectivity was abolished by drug
      application. The main finding was that neuronal inhibition sharpens tuning to the
      modulation frequency in the majority of neurons. In general, changes induced by
      bicuculline or strychnine were comparable.

PMID- 9658030
TI  - Full weight-bearing hindlimb standing following stand training in the adult
      spinal cat.
AB  - Behavioral and physiological characteristics of standing were studied in
      nontrained spinal cats and in spinal cats that received daily stand training of
      the hindlimbs for 12 wk. Training consisted of assisting the cats to stand with
      full weight support either on both hindlimbs or on one hindlimb (30 min/day, 5
      days/wk). Extensor muscle electromyographic (EMG) amplitude and extension at the
      knee and ankle joints during full weight bearing recovered to prespinal levels in
      both stand-trained and nontrained spinal cats. However, full weight bearing of
      the hindquarters was sustained for up to approximately 20 min in the spinal cats
      that received bilateral stand training compared with approximately 4 min in cats
      that were not trained to stand. Unilateral stand training selectively improved
      weight bearing on the trained limb based on ground reaction forces and extensor
      muscle EMG activity levels measured during bilateral standing. These results
      suggest that the capacity of the adult lumbar spinal cord to generate full weight
      bearing standing can be improved by as much as fivefold by the repetitive
      activation of selected neural pathways in the spinal cord after supraspinal
      connectivity has been eliminated. Given that stepping is improved in response to
      step training, it appears that the recovery of standing provides another example
      of training-specific motor learning in the spinal cord, i.e., the spinal cord
      learns to perform hindlimb standing by practicing that specific task.

PMID- 9658031
TI  - Characterization of neuronal migration disorders in neocortical structures. II.
      Intracellular in vitro recordings.
AB  - Neuronal migration disorders (NMD) are involved in a variety of different
      developmental disturbances and in therapy-resistant epilepsy. The cellular
      mechanisms underlying the pronounced hyperexcitability in dysplastic cortex are
      not well understood and demand further clinical and experimental analyses. We
      used a focal freeze-lesion model in cerebral cortex of newborn rats to study the
      functional consequences of NMD. Intracellular recordings from supragranular
      regular spiking cells in cortical slices from adult sham-operated rats revealed
      normal passive and active intrinsic membrane properties and normal stimulus
      evoked excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs,
      respectively). Regular spiking neurons recorded in rat dysplastic cortex showed
      on average a significantly smaller action potential amplitude, a slower spike
      rise, and a less steep primary frequency-current relationship. Stimulus-elicited
      EPSPs in NMD-affected cortex consisted of multiphasic burst discharges, which
      coincided with extracellular field potentials and lasted 150-800 ms. These
      epileptiform responses could be recorded at membrane potentials between -50 and 
      110 mV and were blocked by -2-amino-5-phosphonovaleric acid (APV), indicating the
      involvement of N-methyl--aspartate (NMDA) receptors. Isolated NMDA-mediated and
      APV-sensitive EPSPs could be recorded at membrane potentials negative to -70 mV,
      suggesting that NMDA receptors are activated at relatively negative membrane
      potentials. In comparison with the controls, polysynaptic IPSPs mediated by the
      gamma-aminobutyric acid (GABA) type A and B receptor were either absent or
      reduced in peak conductance in microgyric cortex by 27% (P < 0.05) and 17%,
      respectively. However, monosynaptic IPSPs recorded in the presence of ionotropic
      glutamate receptor antagonists revealed a similar efficacy in NMD and control
      cortex, indicating that GABAergic neurons in microgyric cortex get a weaker
      excitatory input. Our data indicate that the expression of epileptiform activity
      in NMD-affected cortex rather results from an imbalance between excitatory and
      inhibitory synaptic transmission than from alterations in the intrinsic membrane
      properties. This imbalance is caused by an increase in NMDA-receptor-mediated
      excitation in pyramidal neurons and a concurrent decrease of glutamatergic input
      onto inhibitory interneurons.

PMID- 9658032
TI  - Differential effects of the reticulospinal system on locomotion in lamprey.
AB  - Specific effects of stimulating different parts of the reticulospinal (RS) system
      on the spinal locomotor pattern are described in lamprey. In the in vitro brain
      stem and spinal cord preparation, microstimulation in different areas of the
      reticular formation was performed by ejecting a small amount of -glutamate from a
      micropipette. These areas were distributed over the four reticular nuclei of the
      brain stem: the mesencephalic reticular nucleus (MRN) and the anterior, middle
      and posterior rhombencephalic reticular nuclei (ARRN, MRRN, and PRRN,
      respectively). To prevent synaptic spread of excitation within the brain stem,
      the synaptic transmission was blocked by using a low Ca2+, high Mn2+
      physiological saline in the brain stem pool. "Fictive" locomotion was evoked by
      applying N-methyl--aspartate (NMDA) to the spinal cord. Rhythmical discharges of
      motoneurons were recorded bilaterally in the midbody area, from the ventral roots
      that had been subdivided in dorsal and ventral branches, supplying the dorsal and
      ventral part of the myotome, respectively. Two major effects of brain stem
      stimulation were elicited: a change in the frequency of the locomotory rhythm and
      an induction of asymmetry (left/right, dorsal/ventral) in the segmental motor
      output. Approximately 50% of the stimulated sites evoked a change in locomotor
      frequency. In the PRRN almost all effective sites evoked an increase in frequency
      (10-50%). In the other nuclei, increase and decrease (10-30%) were observed
      equally frequently. Most of the stimulated sites (50-80%) in any reticular
      nucleus evoked asymmetry in the segmental motor output. Distortion of the
      segmental output symmetry was classified into eight categories by comparing the
      intensity of locomotor bursts in the dorsal and ventral branches of the two
      ventral roots, ipsilateral and contralateral to the stimulated side. These
      categories differed in the direction of the body flexion, which would be evoked
      during normal swimming: ipsilateral (I), contralateral (C), dorsal (D), ventral
      (V), ipsilateral and dorsal (ID), ipsilateral and ventral (IV), contralateral and
      dorsal (CD), and contralateral and ventral (CV). The different categories were
      not equally represented in each nucleus and across the nuclei. The most
      pronounced categories for each nucleus were as follow. In MRN: I (33%); ARRN: C
      (44%); MRRN: rostral part, I (36%) and caudal part, CV (42%); and PRRN: rostral
      part, I (40%) and caudal part, IV (35%). Other categories were also present but
      less common in each nucleus. To examine if the effects of brain stem stimulation
      were uniform along the spinal cord, recordings were performed from distal parts
      of the cord. Stimulation of a given point in the brain stem produced similar
      pattern of effects in 59% of cases and different patterns in 41% of cases. The
      main conclusion of the present study is that the proportion of RS neurons with
      different influences on the spinal locomotor network differs significantly among
      different parts of the reticular formation of the lamprey. The specificity of RS
      influences may represent a basis for modifications of the segmental locomotor
      output necessary for the control of equilibrium and steering during locomotion.

PMID- 9658033
TI  - Substance P enhances NMDA channel function in hippocampal dentate gyrus granule
      cells.
AB  - Substance P (SP)-containing afferents and the NK-1 tachykinin receptor to which
      SP binds are present in the dentate gyrus of the rat; however, direct actions of
      SP on principal cells have not been demonstrated in this brain region. We have
      examined the effect of SP on N-methyl--aspartate (NMDA) channels from acutely
      isolated dentate gyrus granule cells of adult rat hippocampus to assess the
      ability of SP to regulate glutamatergic input. SP produces a robust enhancement
      of single NMDA channel function that is mimicked by the NK-1-selective agonist
      Sar9, Met(O2)11-SP. The SP-induced prolongation of NMDA channel openings is
      prevented by the selective NK-1 receptor antagonist (+)-(2S, 3S)-3-(2
      methoxybenzylamino)-2-phenylpiperidine (CP-99,994). Calcium influx or activation
      of protein kinase C were not required for the SP-induced increase in NMDA channel
      open durations. The dramatic enhancement of excitatory amino acid-mediated
      excitability by SP places this neuropeptide in a key position to gate activation
      of hippocampal network activity.

PMID- 9658034
TI  - Control of size and excitability of mechanosensory receptive fields in dorsal
      column nuclei by homolateral dorsal horn neurons.
AB  - Both accidental and experimental lesions of the spinal cord suggest that neuronal
      processes occurring in the spinal cord modify the relay of information through
      the dorsal column-lemniscal pathway. How such interactions might occur has not
      been adequately explained. To address this issue, the receptive fields of
      mechanosensory neurons of the dorsal column nuclei were studied before and after
      manipulation of the spinal dorsal horn. After either a cervical or lumbar
      laminectomy and exposure of the dorsal column nuclei in anesthetized cats, the
      representation of the hindlimb or of the forelimb was defined by multiunit
      recordings in both the dorsal column nuclei and in the ipsilateral spinal cord.
      Next, a single cell was isolated in the dorsal column nuclei, and its receptive
      field carefully defined. Each cell could be activated by light mechanical stimuli
      from a well-defined cutaneous receptive field. Generally the adequate stimulus
      was movement of a few hairs or rapid skin indentation. Subsequently a pipette
      containing either lidocaine or cobalt chloride was lowered into the ipsilateral
      dorsal horn at the site in the somatosensory representation in the spinal cord
      corresponding to the receptive field of the neuron isolated in the dorsal column
      nuclei. Injection of several hundred nanoliters of either lidocaine or cobalt
      chloride into the dorsal horn produced an enlargement of the receptive field of
      the neuron being studied in the dorsal column nuclei. The experiment was repeated
      16 times, and receptive field enlargements of 147-563% were observed in 15 cases.
      These data suggest that the dorsal horn exerts a tonic inhibitory control on the
      mechanosensory signals relayed through the dorsal column-lemniscal pathway.
      Because published data from other laboratories have shown that receptive field
      size is controlled by signals arising from the skin, we infer that the control of
      neuronal excitability, receptive field size and location for lemniscal neurons is
      determined by tonic afferent activity that is relayed through a synapse in the
      dorsal horn. This influence of dorsal horn neurons on the relay of mechanosensory
      information through the lemniscal pathways must modify our traditional views
      concerning the relative independence of these two systems.

PMID- 9658035
TI  - Physiological signs of the activation of bag2 and chain intrafusal muscle fibers
      of gastrocnemius muscle spindles in the cat.
AB  - A method is described for identifying the effect of single gamma static
      (gamma(s)) axons on bag2 or chain intrafusal fibers using random (Poisson
      distributed) stimuli. The cross-correlogram of the stimuli with the firing of
      spindle primary afferents took one of three forms. A large, simple, brief
      response was taken to indicate pure chain fiber activation and a small, prolonged
      response to indicate pure bag2 activation. A compound response with brief and
      prolonged components was taken to be a sign of mixed innervation. The correlogram
      components could be well fitted with lognormal curves. They could also be
      transformed into curves of gain as a function of frequency, which were convenient
      for estimating the strength of the effects. In 68 effects of gammas axons on Ia
      afferents, 16 were pure chain, 17 pure bag2, and 35 mixed. This distribution was
      significantly different (P < 0. 05) from that expected from chance nonspecific
      innervation of chain and bag2 fibers. Making use of the estimates of the strength
      of chain and bag2 effects derived from the gain curves, the classification was
      modified by treating mixed responses that had one effect more than five times
      stronger than the other as belonging to the dominant type. The distribution was
      then as follows: chain 16, bag2 28, and mixed 24. This differed very
      significantly from the prediction of chance distribution (P < 0.001). This
      evidence for some degree of specific innervation of chain and bag2 fibers is
      discussed in relation to previous work and with regard to the ways in which the
      two fiber types might be used in natural movements.

PMID- 9658036
TI  - Progression of change in NMDA, non-NMDA, and metabotropic glutamate receptor
      function at the developing corticothalamic synapse.
AB  - The development of receptor function at corticothalamic synapses during the first
      20 days of postnatal development is described. Whole cell excitatory postsynaptic
      currents (EPSCs) were evoked in relay neurons of the ventral posterior nucleus
      (VP) by stimulation of corticothalamic fibers in in vitro slices of mouse brain
      from postnatal day 1 (P1). During P1-P12, excitatory postsynaptic conductances
      showed strong voltage dependence at peak current and at 100 ms after the stimulus
      and were almost completely antagonized by -2-amino-5-phosphonopentoic acid (APV),
      indicating that N-methyl--aspartate (NMDA) receptor-mediated currents dominate
      corticothalamic EPSCs at this time. After P12, in 42% of cells, excitatory
      postsynaptic conductances showed no voltage-dependence at peak current but still
      showed voltage-dependence 100-ms poststimulus. This voltage-dependent conductance
      was antagonized by APV. The nonvoltage-dependent component was APV resistant,
      showed fast decay, and was antagonized by the nonNMDA antagonist, 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX). In the remaining 58% of cells after P12,
      excitatory postsynaptic conductances showed moderate voltage dependence at peak
      conductance and strong voltage dependence 100 ms after the stimulus. Analysis of
      EPSCs before and after APV showed a significant increase in the relative
      contribution of the non-NMDA conductance after the second postnatal week. From P1
      to P16, there was a significant decrease in the time constant of decay of the
      NMDA EPSC but no change in the voltage dependence of the NMDA response. After P8,
      slow EPSPs, 1.5-30 s in duration and mediated by metabotropic glutamate receptors
      (mGluRs), could be evoked by high-frequency stimulation of corticothalamic fibers
      in the presence of APV and CNQX. Similar slow depolarizations could be evoked by
      local application of the mGluR agonist (+/-)-1-aminocyclopentane-trans-1,3
      dicarboxylic acid (t-ACPD) but from P0. Both conductances were blocked by the
      mGluR antagonist, (RS)-alpha-methyl-4-carboxyphenylglycine. Hence functional
      mGluR receptors are present on VP cells from birth, but their synaptic activation
      at corticothalamic synapses can only be detected after P8. In voltage clamp, the
      extrapolated reversal potential of the t-ACPD current, with potassium gluconate
      based internal solution, was +12 +/- 10 (SE) mV, and the measured reversal
      potential with cesium gluconate-based internal solution was 1.5 +/- 9.9 mV,
      suggesting that the mGluR-mediated depolarization was mediated by a nonselective
      cation current. Replacement of NaCl in the external solution caused the reversal
      potential of the current to shift to -18 +/- 2 mV, indicating that Na+ is a
      charge carrier in the current. The current amplitude was not reduced by
      application of Cs+, Ba2+, and Cd2+, indicating that the t-ACPD current was
      distinct from the hyperpolarization-activated cation current (IH) and distinct
      from certain other previously characterized mGluR-activated, nonselective cation
      conductances.

PMID- 9658037
TI  - Limbic gamma rhythms. I. Phase-locked oscillations in hippocampal CA1 and
      subiculum.
AB  - Gamma oscillations (approximately 40 Hz) were induced in transverse hippocampal
      slices by tetanic stimulation of CA1 and/or subiculum. Tetanic stimulation of
      each site elicited population gamma oscillations in the surrounding tissue <400
      micro(m) away. Stimulation of CA1 alone could evoke activity at both CA1 and
      subiculum. Subicular stimulation, however, did not transmit to CA1. When the
      rostral end of CA1 was stimulated, gamma oscillations transmitted across <1.5 mm
      of silent CA1 before reappearing in the subiculum. Tetanic stimulation of CA1
      increased [K+]o to 8.2 +/- 1.5 mM (mean +/- SE). The location of the peak
      increase corresponded to the site of local gamma generation. Silent areas of CA1
      experienced smaller [K+]o increases, to 4.9 +/- 0.7 mM. The subiculum, which
      generated gamma, remained at the baseline 3.0 mM. Although fluctuations in [K+]o
      may have an impact on the generation of gamma rhythms, they are not necessary for
      them. Gamma oscillations had similar frequencies in CA1 and subiculum (40.4 +/-
      2.9 and 43.9 +/- 3.1 Hz, respectively). When present in both, the oscillations
      typically were phase locked with the subiculum lagging by 5.4 +/- 1.8 ms. When
      both CA1 and subiculum were stimulated the lag decreased by 28%. These delays
      approximate those expected for the conduction velocity of axons between the two
      regions, here estimated at 0.52 +/- 0.07 m/s. Transmission of gamma oscillations
      from CA1 to subiculum was blocked by the focal addition of the alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid-receptor antagonist, 6-nitro-7
      sulfamoylbenzo[f]quinoxaline-2,3-dione, to the subiculum. Oscillations induced in
      CA1 by local tetanic stimulation were blocked by focal application of the gamma
      aminobutyric acid-A (GABAA) receptor antagonist, bicuculline, to CA1. Focal
      application of bicuculline to the subiculum blocked gamma due to subicular
      stimulation but not that due to CA1 stimulation. Bath-applied bicuculline
      disrupted subicular gamma evoked by subicular stimulation and led to a transient
      period of epileptiform responses before completely blocking responses. The
      further addition of the GABAB receptor antagonist, CGP 55845A, reversed this
      block, restoring the epileptic discharges evoked by tetanic stimulation. This
      suggests that the subiculum differs from hippocampal CA3 and neocortex, in having
      a powerful GABAB receptor-dependent mechanism to prevent epileptic discharges.
      The subiculum generates gamma rhythms both in response to local stimulation and
      to gamma rhythms evoked in CA1. Subicular gamma differs from that in CA1 in the
      presence of population spike doublets rather than singlets on many cycles. In
      both areas, generation of gamma by local stimulation depends on GABAA receptors,
      suggesting that the subiculum shares the interneuronal network mechanism we
      proposed for CA1.

PMID- 9658038
TI  - Limbic gamma rhythms. II. Synaptic and intrinsic mechanisms underlying spike
      doublets in oscillating subicular neurons.
AB  - Gamma oscillations were evoked in the subiculum in rat transverse hippocampal
      slices by tetanic stimulation (200 ms/100 Hz) of either CA1 or subiculum. Gamma
      oscillations in the subiculum differed from those in CA1 in containing population
      spike doublets as well as singlets. The present study addresses the origin of
      this more complex form of gamma oscillation in the subiculum. Intracellular
      recordings from subicular neurons revealed that 63% of them fired double action
      potentials on cycles of the gamma oscillation that generated population spike
      doublets after tetanic stimulation of either CA1 or subiculum. The remaining
      cells produced excitatory postsynaptic potentials (EPSPs), and occasional single
      spikes, on each cycle. Neurons that fired occasional single action potentials
      during gamma rhythms were "regular spiking" cells. They did not produce burst
      discharges during depolarizing steps, had minimal membrane potential sags on
      hyperpolarizing steps, and responded to single afferent volleys with a single
      action potential on an EPSP followed by a large inhibitory postsynaptic potential
      complex. Fast spiking cells were observed too infrequently to be studied in
      detail. Neurons that fired doublets during gamma rhythms were "intrinsic burst"
      (IB) cells. They generated bursts of action potentials on step membrane
      depolarizations, had significant membrane potential sags on step
      hyperpolarizations with an anodal break potential on return to rest, and fired
      multiple action potentials in response to high-intensity single afferent volleys.
      IB neurons did not fire action potential doublets during 1-s membrane
      depolarizations. Double action potentials, however, were evoked in these cells by
      depolarizing pulses at 40 Hz from hyperpolarized membrane potentials (-100 mV).
      Computer simulations suggest that the hyperpolarization between the
      depolarizations was essential for action potential doublets. The results in this
      and the previous paper suggest the following: either CA1 or subiculum alone can
      generate gamma oscillations gated by local networks of interneurons, oscillations
      in CA1 project through pyramidal cell axons to subiculum with a time lag expected
      from axon conduction delays, and oscillating sequences of EPSPs and intrinsic
      and/or synaptic hyperpolarizing potentials in IB subicular neurons generate gamma
      frequency spike doublets, which depend on both the intrinsic properties of these
      neurons and their temporally patterned synaptic input. This phenomenon could
      amplify gamma output from CA1 and modify its coupling to gamma oscillations in
      the wider limbic system.

PMID- 9658039
TI  - GABAergic inhibition influences auditory motion-direction sensitivity in barn
      owls.
AB  - Many neurons in the barn owl's inferior colliculus (IC) exhibit auditory motion
      direction sensitivity (MDS), i.e., they respond more to motion of a sound source
      in one direction than to motion in the opposite direction. We investigated the
      cellular mechanisms underlying the phenomenon of auditory MDS by
      microiontophoretically applying gamma-aminobutyric acid (GABA) or the GABA
      antagonist bicuculline methiodide (BMI) while recording from neurons in the owl's
      midbrain. In most cases GABA reduced the overall firing rate, whereas BMI
      increased it. In addition, 29% of the motion-direction-sensitive cells completely
      lost their selectivity for the direction of auditory movement during
      administration of BMI. It had been proposed that auditory MDS in the owl is due
      to inhibition. The present results show that GABAergic inhibition plays a role in
      the strengthening of MDS. We discuss the data within the framework of the
      acoustic motion detector and with respect to microiontophoretic studies on visual
      motion detection and on inhibitory mechanisms in the inferior colliculus.

PMID- 9658040
TI  - Effects of mitochondrion on calcium transients at intact presynaptic terminals
      depend on frequency of nerve firing.
AB  - The rate and the total amount of Ca2+ elevation in the presynaptic terminals of
      bullfrog sympathetic ganglia depend on the firing frequency of the terminals.
      Carbonyl cyanide m-chlorophenylhydrazone (CCCP), a mitochondrial uncoupler, was
      used for testing whether mitochondrial Ca2+ uptake is one of the mechanisms that
      underlie this frequency dependence. Fura-2 fluorimetry was used for measurement
      of intraterminal Ca2+. When stimulations of different durations (30 and 1.5 s)
      and frequencies (4 and 20 Hz) evoked Ca2+ transients with similar peak amplitudes
      (264 +/- 22 nM vs. 251 +/- 18 nM, means +/- SE), CCCP augmented the responses to
      the 4-Hz stimulation 8.9 times more strongly than it did the responses to the 20
      Hz stimulation (249.7 +/- 81.5% vs. 25.3 +/- 10.2%). When stimulations delivered
      at the two frequencies had the same durations (1.5, 3, 6, 10, 20, and 30 s), CCCP
      enlarged the responses to the 4-Hz stimulations up to 4.2 times more than it did
      the responses to the 20-Hz stimulations. When the same number of stimuli (120)
      was delivered at the two frequencies, the effects of CCCP on the responses evoked
      by the 4-Hz train were again 6.8 times stronger than its effects on the responses
      to the 20-Hz stimulation. Therefore neither the peak amplitudes of the responses
      nor the durations of the stimulations dictated the extent to which the
      mitochondria modulated the peak [Ca2+]i. Instead, the extent of the modulation
      was governed by the frequency of stimulation. Specifically, the less frequent the
      Ca2+ influx, the stronger the mitochondrial modulation. Also, during nerve firing
      Ca2+ release from the ryanodine-sensitive store had a higher potential to
      influence the [Ca2+]i transients than did Ca2+ removal by the mitochondria for
      the first 6 s of the responses. On cessation of stimulation, CCCP reduced the
      initial rapid rate of Ca2+ decay. Thus uptake by the mitochondria was an
      important mechanism for Ca2+ removal after repetitive firing at the presynaptic
      terminals.

PMID- 9658041
TI  - Endogenous NMDA-receptor activation regulates glutamate release in cultured
      spinal neurons.
AB  - N-methyl--aspartate (NMDA) receptor activation plays a fundamental role in the
      genesis of electrical activity of immature neurons and may participate in
      activity-dependent aspects of CNS development. A recent study has suggested that
      NMDA-receptor-mediated glutamatergic neurotransmission might occur in the
      developing spinal cord via activation of nonsynaptic receptors, but the details
      of NMDA-receptor activation in the developing CNS are not yet well understood. We
      describe here a model of cultured spinal neurons that display ongoing alpha-amino
      3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor activity
      characterized by spontaneous excitatory postsynaptic currents (EPSCs), with NMDA
      receptor activity detectable only as single channel events. -2-amino-5
      phosphonovaleric acid (100 microM) and tetrodotoxin (TTX) 100 nM each reduced the
      occurrence of spontaneous AMPA EPSCs; quantal analysis showed a decrease in the
      number of released quanta but no changes in quantal size, indicating that NMDA
      receptor activation and Na+ channel activity affect the generation of spontaneous
      AMPA EPSCs, at least in part, via mechanisms that impinge on the presynaptic
      terminal. Once the Mg2+-block was released, activity of NMDA receptors
      dramatically increased the release of quantal and multiquantal amounts of
      glutamate, indicating that the NMDA receptors are physiologically coupled to
      glutamate release. In Mg2+-free solution, TTX application elicited an increase in
      the number of quantal AMPA EPSCs and a reduction in the number of multiquantal
      EPSCs, consistent with an effect of NMDA-receptor activation on presynaptic
      terminals. Our results suggest that endogenous activity at a small number of NMDA
      receptors can regulate the release of neurotransmitters at developing AMPA
      synapses.

PMID- 9658042
TI  - Metabotropic glutamate receptor activation modulates sound level processing in
      the cochlear nucleus.
AB  - The principal role of ionotropic glutamate receptors in the transmission and
      processing of information in the auditory pathway has been investigated
      extensively. In contrast, little is known about the functional contribution of
      the G-protein-coupled metabotropic glutamate receptors (mGluRs), although their
      anatomic location suggests that they exercise a significant influence on auditory
      processing. To investigate this issue, sound-evoked responses were obtained from
      single auditory neurons in the cochlear nuclear complex of anesthetized cats and
      gerbils, and metabotropic ligands were administered locally through
      microionophoretic pipettes. In general, microionophoresis of the mGluR agonists,
      (1S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid or (2S,1'S, 2'S)-2
      (carboxycyclopropyl)glycine, initially produced a gradual increase in spontaneous
      and sound-evoked discharge rates. However, activation and recovery times were
      significantly longer than those observed for ionotropic agonists, such as N
      methyl--aspartate or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid,
      consistent with the recruitment of a second-messenger system. The efficacy of
      mGluR agonists was diminished after administration of the mGluR antagonist, (+)
      alpha-methyl-4-carboxyphenylglycine, consistent with a selective action at
      metabotropic recognition sites. In contrast, two distinct changes were observed
      after the mGluR agonist had been discontinued for several minutes. Approximately
      50% of neurons exhibited a chronic depression of sound-evoked discharge rate
      reminiscent of long-term depression, a cellular property observed in other
      systems. Approximately 30% of neurons exhibited a long-lasting enhancement of the
      sound-evoked response similar to the cellular phenomenon of long-term
      potentiation. These findings suggest that mGluR activation has a profound
      influence on the gain of primary afferent driven activity in the caudal cochlear
      nucleus.

PMID- 9658043
TI  - Substance P-induced inward current in identified auditory efferent neurons in rat
      brain stem slices.
AB  - The effects of substance P (SP) on whole cell currents were studied in neurons of
      the medial olivocochlear efferent system (MOCS) in the ventral nucleus of the
      trapezoid body (VNTB) of brain stem slices from neonatal rats. Each neuron was
      identified by retrograde labeling with Fast Blue injected into the cochlea. Bath
      application of SP (0.1-10 microM) reversibly induced an apparent inward current
      in 49 of 63 labeled neurons when voltage clamped at near resting voltages. This
      apparent inward current was consistent with the SP-induced membrane
      depolarization observed in current-clamp mode. The SP-induced change in current
      was dose dependent with a half-maximal response dose of 200 nM. It was mimicked
      by [Cys3,6, Tyr8, Pro9]-SP, a neurokinin (NK1) receptor selective agonist,
      whereas [Succinyl-Asp6, MePhe8]-SP 6-11 (Senktide), a NK3 receptor agonist, had
      no detectable effect. The SP effect was not blocked by 10(-6) M tetrodotoxin
      (TTX) and persisted when the perfusate contained 30 mM tetraethylammonium (TEA)
      or 100 microM Cd2+ or was in a 0-Ca solution. In a TTX-containing solution, SP
      caused a voltage-dependent decrease of membrane conductance, and the SP-evoked
      current reversed at a potential at around -105 mV. The predicted K+ equilibrium
      potential was -93.8 mV under the experimental conditions. The SP-induced inward
      current was attenuated by 66% when the perfusate contained 3 mM Cs+. We conclude
      that the apparent inward current is partly caused by SP decreasing an outward
      current normally maintained by the inward rectifier K+ channels in these cells.
      In the presence of Cs solution in the recording pipette and with a perfusate
      containing 3 mM Cs+, 0.1 mM Cd2+ and 10(-6) M TTX, a residual SP-induced inward
      current was observed at test voltages ranging from -120 to 40 mV. This
      subcomponent reversed its polarity at approximately 20 mV. This inward current
      was reduced substantially (but not abolished) when all NaCl in the external
      solution was replaced by TEA-Cl. The results indicate that SP also opens an
      unknown cation channel, which the available data suggests may be relatively
      nonselective. The results suggest that MOCS neurons are subject to modulation by
      SP, which depolarizes the cell membrane by decreasing the activity of inward
      rectifier K+ channels as well as concurrently activating a separate cation
      conductance. It also was found that in MOCS neurons responsive to both SP and
      norepinephrine, the norepinephrine effect was abolished by TTX, suggesting that
      an interneuronal population excited by norepinephrine converges selectively onto
      SP-sensitive MOCS neurons in the VNTB.

PMID- 9658044
TI  - Responses of deep entorhinal cortex are epileptiform in an electrogenic rat model
      of chronic temporal lobe epilepsy.
AB  - We investigated whether entorhinal cortex (EC) layer IV neurons are
      hyperexcitable in the post-selfsustaining limbic status epilepticus (post-SSLSE)
      animal model of temporal lobe epilepsy. We studied naive rats (n = 44), epileptic
      rats that had experienced SSLSE resulting in spontaneous seizures (n = 45), and
      electrode controls (n = 7). There were no differences between electrode control
      and naive groups, which were pooled into a single control group. Intracellular
      and extracellular recordings were made from deep layers of EC, targeting layer
      IV, which was activated by stimulation of the superficial layers of EC or the
      angular bundle. There were no differences between epileptic and control neurons
      in basic cellular characteristics, and all neurons were quiescent under resting
      conditions. In control tissue, 77% of evoked intracellular responses consisted of
      a short-duration [8.6 +/- 1.3 (SE) ms] excitatory postsynaptic potential and a
      single action potential followed by gamma-aminobutyric acid-A (GABAA) and GABAB
      inhibitory post synaptic potentials (IPSPs). Ten percent of controls did not
      contain IPSPs. In chronically epileptic tissue, evoked intracellular responses
      demonstrated prolonged depolarizing potentials (256 +/- 39 ms), multiple action
      potentials (13 +/- 4), and no IPSPs. Ten percent of epileptic responses were
      followed by rhythmic "clonic" depolarizations. Epileptic responses exhibited an
      all-or-none response to progressive increases in stimulus intensity and required
      less stimulation to elicit action potentials. In both epileptic and control
      animals, intracellular responses correlated precisely in morphology and duration
      with extracellular field potentials. Severing the hippocampus from the EC did not
      alter the responses. Duration of intracellular epileptic responses was reduced
      22% by the N-methyl--aspartate (NMDA) antagonist (-)-2-amino-5-phosphonovaleric
      acid (APV), but they did not return to normal and IPSPs were not restored.
      Epileptic and control responses were abolished by the non-NMDA antagonist 6, 7
      dinitroquinoxaline-2-3-dione (DNQX). A monosynaptic IPSP protocol was used to
      test connectivity of inhibitory interneurons to primary cells by direct
      activation of interneurons with a stimulating electrode placed near the recording
      electrode in the presence of APV and DNQX. Using this protocol, IPSPs similar to
      control (P > 0.05) were seen in epileptic cells. The findings demonstrate that
      deep layer EC cells are hyperexcitable or "epileptiform" in this model.
      Hyperexcitability is not due to interactions with the hippocampus. It is due
      partially to augmented NMDA-mediated excitation. The lack of IPSPs in epileptic
      neurons may suggest inhibition is impaired, but we found evidence that inhibitory
      interneurons are connected to their target cells and are capable of inducing
      IPSPs.

PMID- 9658045
TI  - Distribution of effective synaptic currents in cat triceps surae motoneurons. VI.
      Contralateral pyramidal tract.
AB  - We measured the effective synaptic currents (IN) produced by stimulating the
      contralateral pyramidal tract (PT) in triceps surae motoneurons of the cat. This
      is an oligosynaptic pathway in the cat that generates both excitation and
      inhibition in hindlimb motoneurons. We also determined the effect of the PT
      synaptic input on the discharge rate of some of the motoneurons by inducing
      repetitive firing with long, injected current pulses during which the PT
      stimulation was repeated. At resting potential, all but one triceps motoneuron
      received a net depolarizing effective synaptic current from the PT stimulation.
      The effective synaptic currents (IN) were much larger in putative type F
      motoneurons than in putative type S motoneurons [+4.6 +/- 2.9 (SD) nA for type F
      vs. 0.9 +/- 2.4 nA for putative type S]. When the values of IN at the threshold
      for repetitive firing were estimated, the distribution was markedly altered. More
      than 60% of the putative type S motoneurons received a net hyperpolarizing
      effective synaptic current from the pyramidal tract stimulation as did 33% of the
      putative type F motoneurons. This distribution pattern is very similar to that
      observed previously for the effective synaptic currents produced by stimulating
      the contralateral red nucleus. As would be expected from the wide range of IN
      values at threshold (-4.8 to +8.7 nA), the PT stimulation produced dramatically
      different effects on the discharge of different triceps motoneurons. The
      discharge rates of those motoneurons that received depolarizing effective
      synaptic currents at threshold were accelerated by PT stimulation (+1 to +8
      imp/s), whereas the discharge rates of cells that received hyperpolarizing
      currents were retarded by the PT input (-2 to -7 imp/s). The change in firing
      rates produced by the PT stimulation was generally approximated by the product of
      the effective synaptic currents and the slopes of the motoneurons' frequency
      current relations. Our findings indicate that the contralateral pyramidal tract
      may provide a powerful source of synaptic drive to some high-threshold
      motoneurons while concurrently inhibiting low-threshold cells. Thus this input
      system, like that from the contralateral red nucleus, can potentially alter the
      gain of the input-output function of the motoneuron pool as well as disrupt the
      normal hierarchy of recruitment thresholds.

PMID- 9658046
TI  - Comparison of static fusimotor innervation in cat peroneus tertius and longus
      muscles.
AB  - Static fusimotor innervation was compared in cat peroneus longus and tertius
      muscles because the gamma to spindle ratio is considerably higher in the longus
      (approximately 60 gamma axons for 17 spindles) than in the tertius (approximately
      24 gamma axons for 14 spindles). Single gamma axons were identified as static
      (gamma(s)) by their typical effects on the response of primary ending to ramp
      stretch. The intrafusal muscle fibers that single gamma(s) axons activated in the
      spindles they supplied were identified by the features of cross-correlograms
      between Ia impulses and stimuli, at 100 Hz, and by those of primary ending
      responses during stimulation at 30 Hz. In each experiment, a large proportion of
      the gamma population was tested on about nine spindles. A statistical analysis
      was used to estimate the number of spindles supplied by single gamma(s) axons and
      the proportion of gamma(s) axons that supply only one spindle among those the
      stimulation of which had activated either bag2 or chain fibers alone in a single
      spindle. In peroneus longus, nearly all gamma(s) axons supply one or two
      spindles, whereas in peroneus tertius, the majority of gamma(s) axons supply from
      three to six spindles. The proportion of nonspecifically distributed gamma(s)
      axons, i.e., of axons that supply both bag2 fibers and chain fibers either in the
      same or in different spindles, is much lower (56%) in the longus than in the
      tertius (83%) as previously observed on a population of gammas axons that
      supplied from three to six spindles. Correspondingly, the proportion of specific
      axons is much higher in the longus (44%) than in the tertius (17%). In none of
      the two muscles was a strict relationship observed between the conduction
      velocity of gamma(s) axons and their intrafusal distribution (specific bag2,
      specific chain fibers, nonspecific). However, gamma(s) supplying bag2 fibers
      either specifically or in combination with chain fibers tended to have faster
      conduction velocities, which suggests that, in various motor acts, the proportion
      of activated bag2 and chain fibers may be related to the proportions of activated
      fast and slow gamma(s) axons.

PMID- 9658047
TI  - Analysis of rapid stopping during human walking.
AB  - The mechanisms involved in rapidly terminating human gait were studied. Subjects
      were asked to walk at a comfortable speed and to stop walking as soon as they
      felt an electrical stimulus to the superficial peroneal nerve. This simulated
      hitting an obstacle with the top of the foot. Stimuli were presented repeatedly
      at random during a 20-min period of walking. Electromyograms and joint angular
      movements of the right leg and forces under both feet were recorded. The step
      cycle was divided into 16 parts, and the responses to stimuli in each part were
      analyzed separately. Subjects generally stopped with the right foot in front of
      the left or vice-versa, depending on when the stimulus was applied in the step
      cycle. There was also a transition region in which subjects would rise up on
      their toes and either back down or take one more quick, short forward step. Three
      different mechanisms were used to produce a stop. 1) An extension synergy in the
      swing leg was initiated just before this leg hit the ground to brake the forward
      momentum of the body. 2) The push-off phase of the stance leg was inhibited to
      reduce the forward thrust and maintain the stance leg on the ground behind the
      body. 3) If these mechanisms were insufficient, the body rose up onto the toes of
      the extended forward leg and thereby converted more kinetic energy to potential
      energy. A decision to take an additional step depends on whether the momentum of
      the body is sufficient to carry the center of mass in front of its support on the
      forward leg. If so, an additional step is taken. Despite the complexity of the
      decisions that must be made, changes in electromyographic activity are seen
      throughout the legs and trunk in 150-200 ms.

PMID- 9658048
TI  - Noise from voltage-gated ion channels may influence neuronal dynamics in the
      entorhinal cortex.
AB  - Neurons of the superficial medial entorhinal cortex (MEC), which deliver
      neocortical input to the hippocampus, exhibit intrinsic, subthreshold
      oscillations with slow dynamics. These intrinsic oscillations, driven by a
      persistent Na+ current and a slow outward current, may help to generate the theta
      rhythm, a slow rhythm that plays an important role in spatial and declarative
      learning. Here we show that the number of persistent Na+ channels underlying
      subthreshold oscillations is relatively small (<10(4)) and use a physiologically
      based stochastic model to argue that the random behavior of these channels may
      contribute crucially to cellular-level responses. In acutely isolated MEC neurons
      under voltage clamp, the mean and variance of the persistent Na+ current were
      used to estimate the single channel conductance and voltage-dependent probability
      of opening. A hybrid stochastic-deterministic model was built by using voltage
      clamp descriptions of the persistent and fast-inactivating Na+ conductances,
      along with the fast and slow K+ conductances. All voltage-dependent conductances
      were represented with nonlinear ordinary differential equations, with the
      exception of the persistent Na+ conductance, which was represented as a
      population of stochastic ion channels. The model predicts that the probabilistic
      nature of Na+ channels increases the cell's repertoire of qualitative behaviors;
      although deterministic models at a particular point in parameter space can
      generate either subthreshold oscillations or phase-locked spikes (but rarely
      both), models with an appropriate level of channel noise can replicate
      physiological behavior by generating both patterns of electrical activity for a
      single set of parameters. Channel noise may contribute to higher order interspike
      interval statistics seen in vitro with DC current stimulation. Models with
      channel noise show evidence of spike clustering seen in brain slice experiments,
      although the effect is apparently not as prominent as seen in experimental
      results. Channel noise may contribute to cellular responses in vivo as well; the
      stochastic system has enhanced sensitivity to small periodic stimuli in a form of
      stochastic resonance that is novel (in that the relevant noise source is
      intrinsic and voltage-dependent) and potentially physiologically relevant.
      Although based on a simple model that does not include all known membrane
      mechanisms of MEC stellate cells, these results nevertheless imply that the
      stochastic nature of small collections of molecules may have important effects at
      the cellular and network levels.

PMID- 9658050
TI  - Response to motion in extrastriate area MSTl: center-surround interactions.
AB  - The medial superior temporal area of the macaque monkey extrastriate visual
      cortex can be divided into a dorsal medial (MSTd) and a lateral ventral (MSTl)
      region. The functions of the two regions may not be identical: MSTd may process
      optic flow information that results from the movement of the observer, whereas
      MSTl may be related more closely to processing visual motion related specifically
      to the motion of objects. If MSTl were related to such object motion, one would
      expect to see mechanisms for the segregation of objects from their surround. We
      investigated one of these mechanisms in MSTl neurons: the effect of stimuli
      falling in the region surrounding the receptive field center on the response to
      stimuli falling in the field center. We found the effects of the surround
      stimulation to be modulatory with little response to the surround stimulus itself
      but a clear effect on the response to the stimulus falling on the receptive field
      center. The response to motion in the center in the direction preferred for the
      neuron usually increased when the surround motion was in the opposite direction
      to that in the center and decreased when surround motion was in the same
      direction as that in the center. Fifty-seven percent of the neurons showed a
      ratio of response for center motion with a surround moving in the opposite
      direction to that in the center for center motion alone that was >1. The response
      to motion in the center also increased when the surround stimulus was stationary,
      and this increase was sometimes larger than that with a moving surround. Nearly
      70% of the neurons showed a ratio of response to center motion with a stationary
      surround to center motion alone that was >1. This is in contrast to the minimal
      effect of stationary surrounds in middle temporal area neurons. When the stimulus
      presentation was reversed so that the stimulus in the center was stationary and
      the surround moved, some MSTl neurons responded when the direction of motion in
      the surround was in the direction opposite to the preferred direction of motion
      in the center of the receptive field. Stimulation of the surround thus had a
      profound effect on the response of MSTl neurons, and this pronounced effect of
      the surround is consistent with a role in the segmentation of objects using
      motion.

PMID- 9658049
TI  - Carrier-mediated GABA release activates GABA receptors on hippocampal neurons.
AB  - gamma-Aminobutyric acid (GABA) transporters are electrogenic and sodium-dependent
      and can operate in reverse when cells are depolarized or when there is reversal
      of the inward sodium gradient. However, the functional relevance of this
      phenomenon is unclear. We have examined whether depolarization induced by a
      physiologically relevant increase in extracellular [K+] leads to sufficient
      amounts of carrier-mediated GABA release to activate GABAA receptors on neurons.
      Patch-clamp recordings were made from rat hippocampal neurons in culture with
      solutions designed to isolate chloride currents in the recorded neuron. Pressure
      microejection was used to increase extracellular [K+] from 3 to 12 mM. After
      blockade of vesicular GABA release by removal of extracellular calcium, this
      stimulus induced a large conductance increase in hippocampal neurons [18.9 +/-
      6.8 (SD) nS; n = 16]. This was blocked by the GABAA receptor antagonists
      picrotoxin and bicuculline and had a reversal potential that followed the Nernst
      potential for chloride, indicating that it was mediated by GABAA receptor
      activation. Similar responses occurred after block of vesicular neurotransmitter
      release by tetanus toxin. GABAA receptors also were activated when an increase in
      extracellular [K+] (from 3 to 13 mM) was combined with a reduction in
      extracellular [Na+] or when cells were exposed to a decrease in extracellular
      [Na+] alone. These results indicate that depolarization and/or reversal of the
      Na+ gradient activated GABA receptors via release of GABA from neighboring cells.
      We found that the GABA transporter antagonists 1-(4, 4-diphenyl-3-butenyl)-3
      piperidinecarboxylic acid hydrochloride (SKF89976A; 20-100 microM) and 1-(2
      ([(diphenylmethylene)amino]oxy)ethyl) -1, 2, 5, 6 - tetrahydro - 3 - pyridine -
      carboxylic acid hydrochloride (NO-711; 10 microM) both decreased the responses,
      indicating that the release of GABA resulted from reversal of the GABA
      transporter. We propose that carrier-mediated GABA release occurs in vivo during
      high-frequency neuronal firing and seizures, and dynamically modulates inhibitory
      tone.

PMID- 9658051
TI  - Distinct GABAB actions via synaptic and extrasynaptic receptors in rat
      hippocampus in vitro.
AB  - Intracellular recordings were obtained from pyramidal cells to examine gamma
      aminobutyric acid-B (GABAB)-mediated synaptic mechanisms in the CA1 region of rat
      hippocampal slices. To investigate if heterogeneous ionic mechanisms linked to
      GABAB receptors originate from distinct sets of inhibitory fibers, GABAB-mediated
      monosynaptic late inhibitory postsynaptic potentials (IPSPs) were elicited in the
      presence of antagonists of ionotropic glutamate and GABAA receptors and of an
      inhibitor of GABA uptake and were compared after direct stimulation of inhibitory
      fibers in three different CA1 layers: stratum oriens, radiatum, and lacunosum
      moleculare. No significant differences were found in mean amplitude, rise time,
      or time to decay to half-amplitude of IPSPs evoked from the three layers. Mean
      equilibrium potential (Erev) of late IPSPs was similar for all groups and close
      to the equilibrium potential of K+. Bath application of the GABAB antagonist
      CGP55845A blocked all monosynaptic late IPSPs. During recordings with
      micropipettes containing guanosine-5'-O-(3-thiotriphosphate) (GTPgammaS), the
      mean amplitude of all GABAB IPSPs gradually was reduced. Bath application of Ba2+
      completely eliminated monosynaptic late IPSPs evoked from any of the stimulation
      sites. Late IPSPs were blocked completely during Ba2+ applications that reduced
      the GABAB-mediated hyperpolarizations elicited by local application of exogenous
      GABA only by approximately 50%. These results indicate that heterogenous K+
      conductances activated by GABAB receptors do not originate from separate sets of
      inhibitory fibers in these layers. To examine if synchronous release of GABA from
      a larger number of inhibitory fibers could activate heterogeneous GABAB
      mechanisms, giant GABAB IPSPs were induced by 4-aminopyridine (4-AP) in the
      presence of antagonists of ionotropic glutamate and GABAA receptors. The
      amplitude and time course 4-AP-induced late IPSPs were approximately double that
      of evoked monosynaptic late IPSPs, but their voltage sensitivity, Erev, and
      antagonism by the GABAB antagonist CGP55845A and intracellular GTPgammaS were
      similar. Ba2+ completely abolished 4-AP-induced late IPSPs, whereas responses
      elicited by exogenous GABA were only reduced by approximately 50% in the same
      cells. These results indicate that synchronous activation of large numbers of
      inhibitory fibers, as induced by 4-AP, may not activate heterogenous GABAB
      mediated conductances. Similarly, Ba2+ almost completely blocked late inhibitory
      postsynaptic currents evoked by stimulus trains. Overall, our results show that
      exogenous GABA can activate heterogenous K+ conductances via GABAB receptors, but
      that GABA released synaptically, either by electrical stimulation or 4-AP
      application, can only activate K+ conductances homogeneously sensitive to Ba2+.
      Thus GABAB receptors located at synaptic and extrasynaptic sites on hippocampal
      pyramidal cells may be linked to distinct K+ conductances.

PMID- 9658052
TI  - Decorrelating actions of Renshaw interneurons on the firing of spinal motoneurons
      within a motor nucleus: a simulation study.
AB  - A simulation of spinal motoneurons and Renshaw cells was constructed to examine
      possible functions of recurrent inhibition. Recurrent inhibitory feedback via
      Renshaw cells is known to be weak. In our model, consistent with this, motoneuron
      firing was only reduced by a few pulses per second. Our initial hypothesis was
      that Renshaw cells would suppress synchronous firings of motoneurons caused by
      shared, dynamic inputs. Each motoneuron received an identical pattern of noise in
      its input. Synchrony coefficients were defined as the average motoneuron
      population firing relative to the activity of selected reference motoneurons;
      positive coefficients resulted if the motoneuron population was particularly
      active at the same time the reference motoneuron was active. With or without
      recurrent inhibition, the motoneuron pools tended to show little if any
      synchronization. Recurrent inhibition was expected to reduce the synchrony even
      further. Instead, it reduced the variance of the synchrony coefficients, without
      a comparable effect on the average. This suggests-surprisingly-that both positive
      and negative correlations between motoneurons are suppressed by recurrent
      inhibition. In short, recurrent inhibition may operate as a negative feedback
      mechanism to decorrelate motoneurons linked by common inputs. A consequence of
      this decorrelation is the suppression of spectral activity that apparently arises
      from correlated motoneuron firings due to common excitatory drive. Without
      recurrent inhibition, the power spectrum of the total motoneuron pool firings
      showed a peak at a frequency corresponding to the largest measured firing rates
      of motoneurons in the pool. Recurrent inhibition either reduced or abolished this
      peak, presumably by minimizing the likelihood of correlated firing among pool
      elements. Renshaw cells may act to diminish physiological tremor, by removing
      oscillatory components from aggregate motoneuron activity. Recurrent inhibition
      also improved coherence between the aggregate motoneuron output and the common
      drive, at frequencies above the frequency of the "synchronous" peak. Sensitivity
      analyses demonstrated that the spectral effect became stronger as the duration of
      inhibitory synaptic conductance was shortened with either the magnitude or the
      spatial extent of the inhibitory conductances increased to maintain constant net
      inhibition. Overall, Renshaw inhibition appears to be a powerful way to adjust
      the dynamic behavior of a neuron population with minimal impact on its static
      gain.

PMID- 9658053
TI  - Effects of shape-discrimination training on the selectivity of inferotemporal
      cells in adult monkeys.
AB  - Through extensive training, humans can become "visual experts, " able to visually
      distinguish subtle differences among similar objects with greater ease than those
      who are untrained. To understand the neural mechanisms behind this acquired
      discrimination ability, adult monkeys were fully trained to discriminate 28
      moderately complex shapes. The training effects on the stimulus selectivity of
      cells in area TE of the inferotemporal cortex were then examined in anesthetized
      preparations. Area TE represents a later stage of the ventral visual cortical
      pathway that is known to mediate visual object discrimination and recognition.
      The recordings from the trained monkeys and untrained controls showed that the
      proportion of TE cells responsive to some member of the 28 stimuli was
      significantly greater in the trained monkeys than that in the control monkeys.
      Cell responses recorded from the trained monkeys were not sharply tuned to single
      training stimuli, but rather broadly covered several training stimuli. The
      distances among the training stimuli in the response space spanned by responses
      of the recorded TE cells were significantly greater in the trained monkeys than
      those in the control monkeys. The subset of training stimuli to which individual
      cells responded differed from cell to cell with only partial overlaps, suggesting
      that the cells responded to features common to several stimuli. These results are
      consistent with a model in which visual expertise is acquired through the
      development of differential responses by inferotemporal cells to the images of
      relevant objects.

PMID- 9658054
TI  - Physiological properties of neurons in the optic layer of the rat's superior
      colliculus.
AB  - We made intracellular recordings from 74 neurons in the optic layer of the rat
      superior colliculus (SC). Resting membrane potentials were -62.3 +/- 6.2 (SD) mV,
      and input resistances were 37.9 +/- 10.1 MOmega. Optic layer neurons had large
      sodium spikes (74.2 +/- 12.3 mV) with an overshoot of 12 mV and a half-amplitude
      duration of 0.75 +/- 0.2 ms. Each sodium spike was followed by two
      afterhyperpolarizations (AHPs), one of short duration and one of longer duration,
      which were mediated by tetraethylammonium (TEA)-sensitive (IC) or apamin
      sensitive (IAHP) calcium-activated potassium currents, respectively. Sodium
      spikes were also followed by an afterdepolarization (ADP), which was only
      revealed when the AHPs were blocked by TEA or apamin. In response to
      hyperpolarizing current pulses, optic layer neurons showed an inward
      rectification mediated by H channels. At the break of the current pulse, there
      was a rebound low-threshold spike (LTS) with a short duration of <25 ms. The LTS
      usually induced two sodium spikes (doublet). Most optic layer neurons (84%)
      behaved as intrinsically bursting cells. They responded to suprathreshold
      depolarization with an initial burst (or doublet) followed by a train of regular
      single spikes. The remaining 16% of cells acted as chattering cells with high
      frequency gamma (20-80 Hz) rhythmic burst firing within a narrow range of
      depolarized potentials. The interburst frequency was voltage dependent and also
      time dependent, i.e., showed frequency adaptation. Unmasking the ADP with either
      TEA or apamin converted all of the tested intrinsically bursting cells into
      chattering cells, indicating that the ADP played a crucial role in the generation
      of rhythmic burst firing. Optic layer neurons receive direct retinal excitation
      mediated by both N-methyl--aspartate (NMDA) and non-NMDA receptors. Optic tract
      (OT) stimulation also led to gamma-aminobutyric acid-A (GABAA) receptor-mediated
      inhibition, the main effect of which was to curtail the excitatory response to
      retinal inputs by shunting the excitatory postsynaptic current. Intracellular
      staining with biocytin showed that the optic layer neurons that we recorded from
      were mostly either wide-field vertical neurons or other cells with predominately
      superficially projecting dendrites. These cells were similar to calbindin
      immunoreactive cells seen in the optic layer. The characteristics of these optic
      layer neurons, such as prominent AHPs, strong shunting effect of inhibition, and
      short-lasting LTS, suggest that they respond transiently to retinal inputs. This
      is consistent with a function for these cells as the first relay station in the
      extrageniculate visual pathway.

PMID- 9658055
TI  - Inhibitory synapses among interneurons in the glomerular layer of rat and frog
      olfactory bulbs.
AB  - The patch-clamp technique was applied to periglomerular (PG) cells from slices of
      frog and rat olfactory bulbs to characterize whole cell and single-channel
      properties of inhibitory synaptic currents. Spontaneous and electrically driven
      bicuculline-sensitive synaptic events were recorded under ionic conditions that
      excluded any possible interference of excitatory synapses. The peak amplitude
      distribution of spontaneous events could be fitted by several Gaussians having
      the same interpeak distance. Spontaneous currents reversed polarity at the
      chloride equilibrium potential and were suppressed by 2 mM Co2+; the decay phase
      could be fitted with a single exponential having a time constant of approximately
      10 ms at 0 mV. Bicuculline-sensitive monosynaptic responses could be evoked in PG
      cells by electrical stimulations delivered at the distance of several glomeruli
      within the glomerular layer. Finally, in excised outside-out patches, single
      channel analysis revealed the presence of typical gamma-aminobutyric acid-A
      receptor channels, with a single-channel conductance of 28 pS in symmetrical
      chloride and mean open times of 3-4 ms. The simplest explanation of these data,
      effectively supported by pristine anatomic findings, is that there could be
      inhibitory contacts among interneurons in the glomerular layer.

PMID- 9658056
TI  - Increased calcium buffering in basal forebrain neurons during aging.
AB  - Increased calcium buffering in basal forebrain neurons during aging. J.
      Neurophysiol. 80: 350-364, 1998. Alterations of neuronal calcium (Ca2+)
      homeostasis are thought to underlie many age-related changes in the nervous
      system. Basal forebrain neurons are susceptible to changes associated with aging
      and to related dysfunctions such as Alzheimer's disease. It recently was shown
      that neurons from the medial septum and nucleus of the diagonal band (MS/nDB) of
      aged (24-27 mo) F344 rats have an increased current influx through voltage-gated
      Ca2+ channels (VGCCs) relative to those of young (1-4. 5 mo) rats. Possible age
      related changes in Ca2+ buffering in these neurons have been investigated using
      conventional whole cell and perforated-patch voltage clamp combined with fura-2
      microfluorimetric techniques. Basal intracellular Ca2+ concentrations ([Ca2+]i),
      Ca2+ influx, Ca2+ transients (Delta[Ca2+]i), and time course of Delta[Ca2+]i were
      quantitated, and rapid Ca2+ buffering values were calculated in MS/nDB neurons
      from young and aged rats. The involvement of the smooth endoplasmic reticulum
      (SER) was examined with the SER Ca2+ uptake blocker, thapsigargin. An age-related
      increase in rapid Ca2+ buffering and Delta[Ca2+]i time course was observed,
      although basal [Ca2+]i was unchanged with age. The SER and endogenous diffusible
      buffering mechanisms were found to have roles in Ca2+ buffering, but they did not
      mediate the age-related changes. These findings suggest a model in which some
      aging central neurons could compensate for increased Ca2+ influx with greater
      Ca2+ buffering.

PMID- 9658057
TI  - Spontaneous electromyographic activity in adult rat soleus muscle.
AB  - Single-motor-unit and gross electromyograms (EMG) were recorded from the soleus
      muscle in six unrestrained rats. The median firing frequencies of nine motor
      units were in the 16-25 Hz range, in agreement with previous studies. One
      additional motor unit had a median firing frequency of 47 Hz. This unit and one
      of the lower-frequency units regularly fired doublets. Motor-unit firing
      frequency was well correlated to whole-muscle EMG during locomotion. Integrated
      rectified gross EMG revealed periods of continuous modulation, phasic high
      amplitude events, and tonic low-amplitude segments. The tonic segments typically
      were caused by a small number of motor units firing at stable high frequencies
      (20-30 Hz) for extended periods of time without detectable activity in other
      units. This long-lasting firing in single motor units typically was initiated by
      transient mass activity, which recruited many units. However, only one or a few
      units continued firing at a stable high frequency. The tonic firing terminated
      spontaneously or in conjunction with an episode of mass activity. Different units
      were active in different tonic segments. Thus there was an apparent dissociation
      between activity in different single motor units and consequently between single
      motor-unit activity and whole-muscle EMG. It is proposed that the maintained
      tonic motor-unit activity is caused by intrinsic motoneuron properties in the
      form of depolarizing plateau potentials.

PMID- 9658058
TI  - Multiple second-messenger system modulation of voltage-activated calcium currents
      in teleost retinal horizontal cells.
AB  - Two voltage-activated calcium currents, a transient T-type and a PL-sustained
      type, have been measured in isolated, cultured white bass horizontal cells. These
      two voltage-activated calcium currents were found to be modulated by two
      independent second-messenger systems. Furthermore, activation of either second
      messenger system led to similar changes in calcium current activity. Activation
      of the cyclic AMP second-messenger pathway or the sn-1,2-diacylglycerol (DAG)
      second-messenger system resulted in a significant decrease in the amplitude of
      the transient current and a simultaneous large increase in the amplitude of the
      sustained current. Both second-messenger systems achieved their effects through
      protein phosphorylation. The cyclic AMP pathway resulted in the activation of
      protein kinase A (PKA) and the DAG pathway worked to activate protein kinase C
      (PKC). Two protein kinase inhibitors were analyzed in this study for their
      ability to inhibit second-messenger activated protein kinase activity and
      separate the two pathways. The peptide cyclic AMP-dependent protein kinase
      inhibitor and staurosporine were found to be nonspecific at high concentrations
      and inhibited both second-messenger pathways. At low concentrations however,
      staurosporine specifically inhibited only PKC, whereas adenosine 3',5'-cyclic
      monophosphate (cAMP)-dependent protein kinase inhibitor was selective for PKA.
      Both second-messenger systems were activated by the neuromodulator, dopamine.
      Thus one agonist can initiate multiple second-messenger systems leading to
      similar changes in voltage-activated calcium current activity. The modulatory
      action on calcium currents produced by one second-messenger system added to the
      modulatory action resulting from activation of the other second-messenger system.
      The effect is to alter the magnitude of the horizontal cell calcium currents.

PMID- 9658059
TI  - Corticoreticular pathways in the cat. I. Projection patterns and collaterization.
AB  - This paper summarizes and compares the projection patterns and the receptive
      fields of cortical neurons in areas 4 and 6 that project to the pontomedullary
      reticular formation (PMRF). A total of 326 neurons were recorded in area 4 and
      129 in area 6 in four awake, unrestrained cats that were chronically implanted
      with arrays of electrodes in the PMRF and the pyramidal tract (PT). In area 4,
      47% of the neurons projected to the caudal PT but not to the PMRF (PTNs); 19%
      were activated only from the PMRF [corticoreticular neurons (CRNs)], whereas 27%
      were activated from both the PT and the PMRF (PTN/CRNs). More PTN/CRNs conducted
      at velocities >20 m/s (82%) than did CRNs (23%). In area 6, only 19% of the
      neurons were identified as PTNs, 12% were PTN/CRNs and 31% were CRNs; a further
      38% could not be activated from either structure. Collateral branches within the
      PMRF conducted at maximum velocities of 20 m/s (average = 6.5 m/s). No
      significant differences in the conduction velocities of the collateral branches
      were found either between fast and slow PTNs or between area 4 and area 6
      neurons. A large proportion of neurons in area 4 (85/173, 49%) were activated by
      passive manipulation of the more distal, contralateral forelimb, with
      approximately equal numbers being classed as PTNs, PTN/CRNs and CRNs. Most
      neurons in area 6 for which a receptive field could be found were excited by
      lightly touching or tapping the face and neck; a receptive field could not be
      determined for 39% of the area 6 neurons compared with only 5% of those in area
      4. Finally, there was evidence that neurons in quite widespread areas of the
      pericruciate cortex, including both areas 4 and 6 projected onto similar,
      restricted regions of the PMRF. The fact that the cortical projection from area 4
      to the PMRF includes a high percentage of fast PTNs with a receptive field on the
      distal forelimb is consistent with the view that this projection may serve to
      integrate movement and the dynamic postural adjustments that accompany them. The
      fact that the cortical projection from area 6 to the PMRF is primarily from slow
      PTNs with receptive fields on the face, neck and back is consistent with a role
      for this cortical area in adjusting the general posture of the animal on which
      movements are superimposed.

PMID- 9658060
TI  - Corticoreticular pathways in the cat. II. Discharge activity of neurons in area 4
      during voluntary gait modifications.
AB  - We propose that the descending command from area 4 that is responsible, in part,
      for the change in limb trajectory required to step over an obstacle in one's path
      also plays a role in triggering the anticipatory postural modifications that
      accompany this movement. To test this hypothesis, we recorded the discharge
      characteristics of identified classes of corticofugal neurons in area 4 of the
      cat. Neurons were identified either as: pryamidal tract neurons (PTNs) if their
      axon projected to the caudal pyramidal tract (PT) but not to the pontomedullary
      reticular formation (PMRF); as corticoreticular neurons (CRNs) if their axon
      projected to the PMRF but not to the PT; and as PTN/CRNs if their axon projected
      to both structures. Altogether, the discharge properties of 212 corticofugal
      neurons (109 PTNs, 66 PTN/CRNs, and 37 CRNs) within area 4 were recorded during
      voluntary gait modifications. Neurons in all three classes showed increases in
      their discharge frequency during locomotion and included groups that increased
      their discharge either during the swing phase of the modified step, during the
      subsequent stance phase, or in the stance phase of the cycle preceding the step
      over the obstacle. A slightly higher percentage of CRNs (39%) discharged in the
      stance phase prior to the gait modification than did the PTNs or PTN/CRNs (20%
      and 17% respectively). In 37 electrode penetrations, we were able to record
      clusters of 3 or more neurons within 500 micro(m) of each other. In most cases,
      PTN/CRNs recorded in close proximity to PTNs had similar receptive fields and
      discharged in a similar, but not identical, manner during the gait modifications.
      Compared with adjacent PTNs, CRNs normally showed a more variable pattern of
      activity and frequently discharged earlier in the step cycle than did the PTNs or
      PTN/CRNs. We interpret the results as providing support for the original
      hypothesis. We suggest that the collateral branches to the PMRF from corticofugal
      neurons with axons that continue at least as far as the caudal PT provide a
      signal that could be used to trigger dynamic postural responses that are
      appropriately organized and scaled for the movements that are being undertaken.
      We suggest that the more variable and earlier discharge activity observed in CRNs
      might be used to modify the postural support on which the movements and the
      dynamic postural adjustments are superimposed.

PMID- 9658061
TI  - Interactions between idiothetic cues and external landmarks in the control of
      place cells and head direction cells.
AB  - Two types of neurons in the rat brain have been proposed to participate in
      spatial learning and navigation: place cells, which fire selectively in specific
      locations of an environment and which may constitute key elements of cognitive
      maps, and head direction cells, which fire selectively when the rat's head is
      pointed in a specific direction and which may serve as an internal compass to
      orient the cognitive map. The spatially and directionally selective properties of
      these cells arise from a complex interaction between input from external
      landmarks and from idiothetic cues; however, the exact nature of this interaction
      is poorly understood. To address this issue, directional information from visual
      landmarks was placed in direct conflict with directional information from
      idiothetic cues. When the mismatch between the two sources of information was
      small (45 degrees), the visual landmarks had robust control over the firing
      properties of place cells; when the mismatch was larger, however, the firing
      fields of the place cells were altered radically, and the hippocampus formed a
      new representation of the environment. Similarly, the visual cues had control
      over the firing properties of head direction cells when the mismatch was small
      (45 degrees), but the idiothetic input usually predominated over the visual
      landmarks when the mismatch was larger. Under some conditions, when the visual
      landmarks predominated after a large mismatch, there was always a delay before
      the visual cues exerted their control over head direction cells. These results
      support recent models proposing that prewired intrinsic connections enable
      idiothetic cues to serve as the primary drive on place cells and head direction
      cells, whereas modifiable extrinsic connections mediate a learned, secondary
      influence of visual landmarks.

PMID- 9658062
TI  - Spatiotemporal patterns at the retinal output.
AB  - Edge enhancement in the retina is thought to be mediated by classical center
      surround antagonism, first encountered as the interactions between horizontal
      cells and cones. But in the salamander retina these interactions do little to
      enhance edges. Instead, a robust dynamic interaction between amacrine and bipolar
      cells appears to be responsible for a sharp edge enhancement. To demonstrate this
      we recorded extracellularly from a single ganglion cell and moved a flashed
      square, 300 micro(m) on a side, over a 1.5 x 1.0 mm2 grid at 25-micro(m)
      increments. Playing back all of these recordings simultaneously simulated the
      pattern of responses that would have been measured from an array of ganglion
      cells. The emerging pattern of ganglion cell activity first faithfully
      represented the flashed square, but after approximately 60 ms the center of the
      representation collapsed, leaving a representation of only the edges. We inferred
      that the feedback synapse from amacrine to bipolar cells at gamma-aminobutyric
      acid-C (GABAC) receptors mediated this effect: bicuculline and strychnine were
      ineffective in altering the response pattern, but in picrotoxin the center of the
      representation did not collapse. The GABAergic amacrine cells thought to mediate
      this effect have quite narrow spread of processes, so the existence of this edge
      enhancing effect suggests a mechanism quite different from classical lateral
      inhibition, namely the delayed inhibition of a spatially expanding input pattern.

PMID- 9658063
TI  - Cell-permeable scavengers of superoxide prevent long-term potentiation in
      hippocampal area CA1.
AB  - Long-term potentiation (LTP) in hippocampal area CA1 is generally dependent on N
      methyl--aspartate (NMDA) receptor activation. Reactive oxygen species (ROS),
      including superoxide, are produced in response to NMDA receptor activation in a
      number of brain regions, including the hipppocampus. In this study, two cell
      permeable manganese porphyrin compounds that mimic superoxide dismutase (SOD)
      were used to determine whether production of superoxide is required for the
      induction of LTP in area CA1 of rat hippocampal slices. Incubation of hippocampal
      slices with either Mn(III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) or
      Mn(III) tetrakis (1-methyl-4-pyridyl) porphyrin (MnTMPyP) prevented the induction
      of LTP. Incubation of slices with either light-inactivated MnTBAP or light
      inactivated MnTMPyP had no effect on induction of LTP. Neither MnTBAP nor MnTMPyP
      was able to reverse preestablished LTP. These observations suggest that
      production of superoxide occurs in response to LTP-inducing stimulation and that
      superoxide is necessary for the induction of LTP.

PMID- 9658064
TI  - Deficits in smooth-pursuit eye movements after muscimol inactivation within the
      primate's frontal eye field.
AB  - To evaluate smooth-pursuit (SP) function in the primate frontal eye field (FEF),
      microinjections of muscimol, a gamma-aminobutyric acid (GABA) agonist, were used
      to reversibly deactivate physiologically characterized sites in FEF. SP was
      severely impaired by deactivation at sites in the FEF's smooth eye movement
      region (FEFsem) located in the fundus and posterior bank of the macaque monkey's
      arcuate sulcus. These SP deficits were apparent immediately after the muscimol
      injection and persisted for several hours but recovered by the next day. SP was
      most drastically and consistently impaired for directions similar to the injected
      site's elicited smooth eye movement direction or to the optimal SP direction for
      its neuronal responses. Targets moving in these directions, usually ipsilateral
      to the injected hemisphere, were tracked primarily with saccades after the
      muscimol injection, the peak SP velocity being only 10-30% of preinjection
      velocity. SP in other directions, including contralateral, was less strongly
      affected. Initial SP acceleration in response to target motion onset was also
      significantly diminished, generally by approximately the same proportion as peak
      SP velocity. In contrast, saccades were largely unaffected by muscimol injections
      in FEFsem; nor was there an immediate effect on SP when control sites in the
      saccadic region of FEF (FEFsac) were deactivated, although a SP deficit often
      appeared 30-60 min after FEFsac injections, possibly reflecting diffusion of
      muscimol into neighboring FEFsem. These reversible SP deficits produced by
      muscimol inactivation within FEFsem are similar to permanent deficits caused by
      large aspiration lesions of FEF and indicate that inclusion of FEFsem is the
      critical factor determining whether FEF lesions impair SP. The severity of the
      reversible deficits found here indicates how extremely critical FEFsem is for
      normal highgain SP.

PMID- 9658065
TI  - Role of the Fas/Fas ligand apoptotic pathway in human immunodeficiency virus type
      1 disease.

PMID- 9658066
TI  - Attenuation of influenza A virus mRNA levels by promoter mutations.
AB  - We have engineered influenza A/WSN/33 viruses which have viral RNA (vRNA)
      segments with altered base pairs in the conserved double-stranded region of their
      vRNA promoters. The mutations were introduced into the segment coding for the
      neuraminidase (NA) by using a reverse genetics system. Two of the rescued viruses
      which share a C-G-->A-U double mutation at positions 11 and 12' at the 3' and 5'
      ends of the NA-specific vRNA, respectively, showed approximately a 10-fold
      reduction of NA levels. The mutations did not dramatically affect the NA-specific
      vRNA levels found in virions or the NA-specific vRNA and cRNA levels in infected
      cells. In contrast, there was a significant decrease in the steady-state levels
      of NA-specific mRNAs in infected cells. Transcription studies in vitro with
      ribonucleoprotein complexes isolated from the two transfectant viruses indicated
      that transcription initiation of the NA-specific segment was not affected.
      However, the majority of NA-specific transcripts lacked poly(A) tails, suggesting
      that mutations in the double-stranded region of the influenza virus vRNA promoter
      can attenuate polyadenylation of mRNA molecules. This is the first time that a
      promoter mutation in an engineered influenza virus has shown a differential
      effect on influenza virus RNA transcription and replication.

PMID- 9658067
TI  - The herpesvirus transactivator VP16 mimics a human basic domain leucine zipper
      protein, luman, in its interaction with HCF.
AB  - In human cells infected with herpes simplex virus (HSV), viral gene expression is
      initiated by the virion protein VP16. VP16 does not bind DNA directly but forms a
      multiprotein complex on the viral immediate-early gene promoters with two
      cellular proteins: the POU domain protein Oct-1 and host cell factor (HCF; also
      called C1, VCAF, and CFF). Despite its apparent role in stabilizing the VP16
      induced transcription complex, the natural biological role of HCF is unclear.
      Only recently HCF has been implicated in control of the cell cycle. To determine
      the role of HCF in cells and answer why HSV has evolved an HCF-dependent
      mechanism for the initiation of the lytic cycle, we identified the first human
      ligand for HCF (R. Lu et al., Mol. Cell. Biol. 17:5117-5126, 1997). This protein,
      Luman, is a member of the CREB/ATF family of transcription factors that can
      activate transcription from promoters containing cyclic AMP response elements
      (CRE). Here we provide evidence that Luman and VP16 share two important
      structural features: an acidic activation domain and a common mechanism for
      binding HCF. We found that Luman, its homolog in Drosophila, dCREB-A (also known
      as BBF-2), and VP16 bind to HCF by a motif, (D/E)HXY(S/A), present in all three
      proteins. In addition, a mutation (P134S) in HCF that prevents VP16 binding also
      abolishes its binding to Luman and dCREB-A. We also show that while interaction
      with HCF is not required for the ability of Luman to activate transcription when
      tethered to the GAL4 promoter, it appears to be essential for Luman to activate
      transcription through CRE sites. These data suggest that the HCF-Luman
      interaction may represent a conserved mechanism for transcriptional regulation in
      metazoans, and HSV mimics this interaction with HCF to monitor the physiological
      state of the host cell.

PMID- 9658068
TI  - A subset of porcine reproductive and respiratory syndrome virus GP3 glycoprotein
      is released into the culture medium of cells as a non-virion-associated and
      membrane-free (soluble) form.
AB  - The GP3 protein of the IAF-Klop strain of porcine reproductive and respiratory
      syndrome virus (PRRSV) was expressed in 293 cells by a recombinant human type 5
      adenovirus carrying the open reading frame 3 gene. The protein exhibited a
      molecular mass of 42 kDa and comigrated with GP3 expressed in PRRSV-infected MARC
      145 cells. Removal of N-linked glycans from GP3 resulted in a 27-kDa protein
      (P3), confirming its highly glycosylated nature. Pulse-chase experiments carried
      out either in the context of PRRSV infection or upon individual expression of GP3
      in 293 cells showed that the protein remains completely endo-beta-N
      acetylglucosaminidase H-sensitive even after 4 h of synthesis. Thus, the
      transport of GP3 was restricted to the premedial Golgi compartment, presumably
      the endoplasmic reticulum (ER). However, a minor fraction of GP3 was found to be
      secreted in the culture medium as a soluble membrane-free form. This released
      protein (sGP3) was readily identified upon individual expression of GP3 in 293
      cells as well as in the context of PRRSV infection, albeit at lower levels. The
      sGP3 migrated as a smear and displayed a molecular mass ranging from 43 to 53
      kDa. The unglycosylated form of sGP3 comigrated with its intracellular
      deglycosylated counterpart, suggesting that the release from the cell of a subset
      of GP3 did not result from cleavage of a putative membrane-anchor sequence.
      Strikingly, unlike GP3, the sGP3 acquired Golgi-specific modifications of its
      carbohydrate side chains and folded into a disulfide-linked homodimer. Brefeldin
      A treatment completely abolished the release of sGP3, suggesting that the ER-to
      Golgi compartment is an obligatory step in cellular secretion of sGP3. In
      contrast, 10 mM monensin did not prevent sGP3 release but inhibited the terminal
      glycosylation that confers on the protein its diffuse pattern. Since GP3 was
      found to be nonstructural in the case of the North American strain, secretion of
      a minor fraction of GP3 might be an explanation for its high degree of
      immunogenicity in infected pigs. Furthermore, this secreted protein might be
      relevant as a model for further studies on the cellular subcompartments involved
      in the sorting of proteins to the extracellular milieu.

PMID- 9658069
TI  - Characterization of a cis-acting sequence in the Pol region required to transfer
      human foamy virus vectors.
AB  - To identify cis-acting elements in the foamy virus (FV) RNA pregenome, we
      developed a transient-vector-production system based on cotransfection of
      indicator gene-bearing vector and gag-pol and env expression plasmids. Two
      elements which were critical for vector transfer were found and mapped
      approximately. The first element was located in the RU5 leader and the 5' gag
      region (approximately up to position 650 of the viral RNA). The second element
      was located in an approximately 2-kb sequence in the 3' pol region. Although
      small 5' and 3' deletions, as well as internal deletions of the latter element,
      were tolerated, both elements were found to be absolutely required for vector
      transfer. The functional characterization of the pol region-located cis-acting
      element revealed that it is essential for efficient incorporation or the
      stability of particle-associated virion RNA. Furthermore, virions derived from a
      vector lacking this sequence were found to be deficient in the cleavage of the
      Gag protein by the Pol precursor protease. Our results suggest that during the
      formation of infectious virions, complex interactions between FV Gag and Pol and
      the viral RNA take place.

PMID- 9658070
TI  - Inhibition of simian immunodeficiency virus (SIV) replication by CD8(+) T
      lymphocytes from macaques immunized with live attenuated SIV.
AB  - Characterization of immune responses induced by live attenuated simian
      immunodeficiency virus (SIV) strains may yield clues to the nature of protective
      immunity induced by this vaccine approach. We investigated the ability of CD8(+)
      T lymphocytes from rhesus macaques immunized with the live, attenuated SIV strain
      SIVmac239Deltanef or SIVmac239Delta3 to inhibit SIV replication. CD8(+) T
      lymphocytes from immunized animals were able to potently suppress SIV replication
      in autologous SIV-infected CD4(+) T cells. Suppression of SIV replication by
      unstimulated CD8(+) T cells required direct contact and was major
      histocompatibility complex (MHC) restricted. However, CD3-stimulated CD8(+) T
      cells produced soluble factors that inhibited SIV replication in an MHC
      unrestricted fashion as much as 30-fold. Supernatants from stimulated CD8(+) T
      cells were also able to inhibit replication of both CCR5- and CXCR4-dependent
      human immunodeficiency virus type 1 (HIV-1) strains. Stimulation of CD8(+) cells
      with cognate cytotoxic T-lymphocyte epitopes also induced secretion of soluble
      factors able to inhibit SIV replication. Production of RANTES, macrophage
      inhibitory protein 1alpha (MIP-1alpha), or MIP-1beta from stimulated CD8(+) T
      cells of vaccinated animals was almost 10-fold higher than that from stimulated
      CD8(+) T cells of control animals. However, addition of antibodies that
      neutralize these beta-chemokines, either alone or in combination, only partly
      blocked inhibition of SIV and HIV replication by soluble factors produced by
      stimulated CD8(+) T cells. Our results indicate that inhibition of SIV
      replication by CD8(+) T cells from animals immunized with live attenuated SIV
      strains involves both MHC-restricted and -unrestricted mechanisms and that MHC
      unrestricted inhibition of SIV replication is due principally to soluble factors
      other than RANTES, MIP-1alpha, and MIP-1beta.

PMID- 9658071
TI  - Mouse adenovirus type 1 early region 1A is dispensable for growth in cultured
      fibroblasts.
AB  - Mouse adenovirus type 1 (MAV-1) mutants with deletions of conserved regions of
      early region 1A (E1A) or with point mutations that eliminate translation of E1A
      were used to determine the role of E1A in MAV-1 replication. MAV-1 E1A mutants
      expressing no E1A protein grew to titers comparable to wild-type MAV-1 titers on
      mouse fibroblasts (3T6 fibroblasts and fibroblasts derived from Rb+/+, Rb+/-, and
      Rb-/- transgenic embryos). To test the hypothesis that E1A could induce a
      quiescent cell to reenter the cell cycle, fibroblasts were serum starved to stop
      DNA replication and cellular replication and then infected with the E1A mutant
      and wild-type viruses. All grew to equivalent titers. Steady-state levels of MAV
      1 early mRNAs (E1A, E1B, E2, E3, and E4) from 3T6 cells infected with wild-type
      or E1A mutant virus were examined by Northern analysis. Steady-state levels of
      mRNAs from the mutant-infected cells were comparable to or greater than the
      levels found in wild-type virus infections for most of the early regions and for
      two late genes. The E2 mRNA levels were slightly reduced in all mutant infections
      relative to wild-type infections. E1A mRNA was not detected from infections with
      the MAV-1 E1A null mutant, pmE109, or from infections with similar MAV-1 E1A null
      mutants, pmE112 and pmE113. The implications for the lack of a requirement of E1A
      in cell culture are discussed.

PMID- 9658072
TI  - Determinants of human immunodeficiency virus type 1 envelope glycoprotein
      activation by soluble CD4 and monoclonal antibodies.
AB  - Infection by some human immunodeficiency virus type 1 (HIV-1) isolates is
      enhanced by the binding of subneutralizing concentrations of soluble receptor,
      soluble CD4 (sCD4), or monoclonal antibodies directed against the viral envelope
      glycoproteins. In this work, we studied the abilities of different antibodies to
      mediate activation of the envelope glycoproteins of a primary HIV-1 isolate, YU2,
      and identified the regions of gp120 envelope glycoprotein contributing to
      activation. Binding of antibodies to a variety of epitopes on gp120, including
      the CD4 binding site, the third variable (V3) loop, and CD4-induced epitopes,
      enhanced the entry of viruses containing YU2 envelope glycoproteins. Fab
      fragments of antibodies directed against either the CD4 binding site or V3 loop
      also activated YU2 virus infection. The activation phenotype was conferred on the
      envelope glycoproteins of a laboratory-adapted HIV-1 isolate (HXBc2) by replacing
      the gp120 V3 loop or V1/V2 and V3 loops with those of the YU2 virus. Infection by
      the YU2 virus in the presence of activating antibodies remained inhibitable by
      macrophage inhibitory protein 1beta, indicating dependence on the CCR5 coreceptor
      on the target cells. Thus, antibody enhancement of YU2 entry involves neither Fc
      receptor binding nor envelope glycoprotein cross-linking, is determined by the
      same variable loops that dictate enhancement by sCD4, and probably proceeds by a
      process fundamentally similar to the receptor-activated virus entry pathway.

PMID- 9658073
TI  - Cellular components interact with adenovirus type 5 minimal DNA packaging
      domains.
AB  - Adenovirus type 5 DNA packaging is initiated from the left end of the viral
      genome and depends on the presence of a cis-acting packaging domain located
      between nucleotides 194 and 380. Multiple redundant packaging elements (termed A
      repeats I through VII [AI through AVII]) are contained within this domain and
      display differential abilities to support DNA packaging in vivo. The functionally
      most important repeats, AI, AII, AV, and AVI, follow a bipartite consensus motif
      exhibiting AT-rich and CG-rich core sequences. Results from previous mutational
      analyses defined a fragment containing AV, AVI, and AVII as a minimal packaging
      domain in vivo, which supports a functional independence of the respective cis
      acting sequences. Here we describe multimeric versions of individual packaging
      elements as minimal packaging domains that can confer viability and packaging
      activity to viruses carrying gross truncations within their left end. These
      mutant viruses directly rate the functional role that different packaging
      elements play relative to each other. The A repeats are likely to be binding
      sites for limiting, trans-acting packaging factors of cellular and/or viral
      origin. We report here the characterization of two cellular binding activities
      interacting with all of the minimal packaging domains in vitro, an unknown
      binding activity termed P-complex, and the transcription factor chicken ovalbumin
      upstream promoter transcription factor. The binding of both activities is
      dependent on the integrity of the AT-rich, but not the CG-rich, consensus half
      site. In the case of P-complex, binding affinity for different minimal packaging
      domains in vitro correlates well with their abilities to support DNA packaging in
      vivo. Interestingly, P-complex interacts not only with packaging elements but
      also with the left terminus of the viral genome, the core origin of replication.
      Our data implicate cellular factors as components of the viral packaging
      machinery. The dual binding specificity of P-complex for packaging and
      replication sequences may further suggest a direct involvement of left-end
      replication sequences in viral DNA encapsidation.

PMID- 9658074
TI  - Phosphorylation of p53: a novel pathway for p53 inactivation in human T-cell
      lymphotropic virus type 1-transformed cells.
AB  - Inhibition of p53 function, through either mutation or interaction with viral or
      cellular transforming proteins, correlates strongly with the oncogenic potential.
      Only a small percentage of human T-cell lymphotropic virus type 1 (HTLV-1)
      transformed cells carry p53 mutations, and mutated p53 genes have been found in
      only one-fourth of adult T-cell leukemia cases. In previous studies, we
      demonstrated that wild-type p53 is stabilized and transcriptionally inactive in
      HTLV-1-transformed cells. Further, the viral transcriptional activator Tax plays
      a role in both the stabilization and inactivation of p53 through a mechanism
      involving the first 52 amino acids of p53. Here we show for the first time that
      phosphorylation of p53 inactivates p53 by blocking its interaction with basal
      transcription factors. Using two-dimensional peptide mapping, we demonstrate that
      peptides corresponding to amino acids 1 to 19 and 387 to 393 are
      hyperphosphorylated in HTLV-1-transformed cells. Moreover, using antibodies
      specific for phosphorylated Ser15 and Ser392, we demonstrate increased
      phosphorylation of these amino acids. Since HTLV-1 p53 binds DNA in a sequence
      specific manner but fails to interact with TFIID, we tested whether
      phosphorylation of the N terminus of p53 affected p53-TFIID interaction. Using
      biotinylated peptides, we show that phosphorylation of Ser15 alone inhibits p53
      TFIID interaction. In contrast, phosphorylation at Ser15 and -37 restores TFIID
      binding and blocks MDM2 binding. Our studies provide evidence that HTLV-1
      utilizes the posttranslational modification of p53 in vivo to inactivate function
      of the tumor suppressor protein.

PMID- 9658075
TI  - In vitro cell-free conversion of noninfectious Moloney retrovirus particles to an
      infectious form by the addition of the vesicular stomatitis virus surrogate
      envelope G protein.
AB  - In the absence of envelope gene expression, retrovirus packaging cell lines
      expressing Moloney murine leukemia virus (MLV) gag and pol genes produce large
      amounts of noninfectious virus-like particles that contain reverse transcriptase,
      processed Gag protein, and viral RNA (gag-pol RNA particles). We demonstrate that
      these particles can be made infectious in an in vitro, cell-free system by the
      addition of a surrogate envelope protein, the G spike glycoprotein of vesicular
      stomatitis virus (VSV-G). The appearance of infectivity is accompanied by
      physical association of the G protein with the immature, noninfectious virus
      particles. Similarly, exposure in vitro of wild-type VSV-G to a fusion-defective
      pseudotyped virus containing a mutant VSV-G markedly increases the infectivity of
      the virus to titers similar to those of conventional VSV-G pseudotyped viruses.
      Furthermore, similar treatment of an amphotropic murine leukemia virus
      significantly allows infection of BHK cells not otherwise susceptible to
      infection with native amphotropic virus. The partially cell-free virus maturation
      system reported here should be useful for studies aimed at the preparation of
      tissue-targeted retrovirus vectors and will also aid in studies of nucleocapsid
      envelope interactions during budding and of virus assembly and virus-receptor
      interactions during virus uptake into infected cells. It may also represent a
      potentially useful step toward the eventual development of a completely cell-free
      retrovirus assembly system.

PMID- 9658076
TI  - Multiple virulence determinants of foot-and-mouth disease virus in cell culture.
AB  - Hypervirulent variants of foot-and-mouth disease virus (FMDV) of serotype C arise
      upon serial cytolytic or persistent infections in cell culture. A specific
      mutation in the internal ribosome entry site of persistent FMDV was previously
      associated with enhanced translation initiation activity that could contribute to
      the hypervirulent phenotype for BHK-21 cells. Here we report that several
      hypervirulent FMDV variants arising upon serial cytolytic passage show an
      invariant internal ribosome entry site but have a number of mutations affecting
      structural and nonstructural viral proteins. The construction of chimeric type O
      type C infectious transcripts has allowed the mapping of a major determinant of
      hypervirulence to the viral capsid. Tissue culture-adapted FMDV displayed
      enhanced affinity for heparin, but binding to cell surface heparan sulfate
      moieties was not required for expression of the hypervirulent phenotype in
      Chinese hamster ovary (CHO) cells. Virulence was identical or even higher for
      glycosaminoglycan-deficient CHO cells than for wild-type CHO cells. FMDV variants
      with decreased affinity for heparin were selected from a high-binding parental
      population and analyzed. Substitutions associated with decreased heparin binding
      were located at positions 173 of capsid protein VP3 and 144 of capsid protein
      VP1. These substitutions had a moderate effect on virulence for BHK-21 cells but
      completely abrogated infection of CHO cells. The comparative results with several
      FMDV isolates show that (i) increased affinity for heparin and alterations in
      cell tropism may be mediated by a number of independent sites on the viral capsid
      and (ii) the same capsid modifications may have different effects on different
      cell types.

PMID- 9658077
TI  - Molecular mechanisms of serum resistance of human influenza H3N2 virus and their
      involvement in virus adaptation in a new host.
AB  - H3N2 human influenza viruses that are resistant to horse, pig, or rabbit serum
      possess unique amino acid mutations in their hemagglutinin (HA) protein. To
      determine the molecular mechanisms of this resistance, we characterized the
      receptor-binding properties of these mutants by measuring their affinity for
      total serum protein inhibitors and for soluble receptor analogs. Pig serum
      resistant variants displayed a markedly decreased affinity for total pig serum
      sialylglycoproteins (which contain predominantly 2-6 linkage between sialic acid
      and galactose residues) and for the sialyloligosaccharide 6'-sialyl(N
      acetyllactosamine). These properties correlated with the substitution 186S-->I in
      HA1. The major inhibitory activity in rabbit serum was found to be a beta
      inhibitor with characteristics of mannose-binding lectins. Rabbit serum-resistant
      variants exhibited decreased sensitivity to this inhibitor due to the loss of a
      glycosylation sequon at positions 246 to 248 of the HA. In addition to a somewhat
      reduced affinity for 6'-sialyl(N-acetyllactosamine)-containing receptors, horse
      serum-resistant variants lost the ability to bind the viral neuraminidase
      resistant 4-O-acetylated sialic acid moieties of equine alpha2-macroglobulin
      because of the mutation 145N-->K/D in their HA1. These results indicate that
      influenza viruses become resistant to serum inhibitors because their affinity for
      these inhibitors is reduced. To determine whether natural inhibitors play a role
      in viral evolution during interspecies transmission, we compared the receptor
      binding properties of H3N8 avian and equine viruses, including two strains
      isolated during the 1989 to 1990 equine influenza outbreak, which was caused by
      an avian virus in China. Avian strains bound 4-O-acetylated sialic acid residues
      of equine alpha2-macroglobulin, whereas equine strains did not. The earliest
      avian-like isolate from a horse influenza outbreak bound to this sialic acid with
      an affinity similar to that of avian viruses; a later isolate, however, displayed
      binding properties more similar to those of classical equine strains. These data
      suggest that the neuraminidase-resistant sialylglycoconjugates present in horses
      exert selective pressure on the receptor-binding properties of avian virus HA
      after its introduction into this host.

PMID- 9658078
TI  - Determinants for sensitivity of human immunodeficiency virus coreceptor CXCR4 to
      the bicyclam AMD3100.
AB  - The bicyclam AMD3100 is a potent and selective inhibitor of the replication of
      human immunodeficiency virus type 1 and type 2 (HIV-1 and HIV-2). It was recently
      demonstrated that the compound inhibited HIV entry through CXCR4 but not through
      CCR5. Selectivity of AMD3100 for CXCR4 was further indicated by its lack of
      effect on HIV-1 and HIV-2 infection mediated by the CCR5, CCR3, Bonzo, BOB, and
      US28, coreceptors. AMD3100 completely blocked HIV-1 infection mediated by a
      mutant CXCR4 bearing a deletion of most of the amino-terminal extracellular
      domain. In contrast, relative resistance to AMD3100 was conferred by different
      single amino acid substitutions in the second extracellular loop (ECL2) or in the
      adjacent membrane-spanning domain, TM4. Only substitutions of a neutral residue
      for aspartic acid and of a nonaromatic residue for phenylalanine (Phe) were
      associated with drug resistance. This suggests a direct interaction of AMD3100
      with these amino acids rather than indirect effects of their mutation on the
      CXCR4 structure. The interaction of aspartic acids of ECL2 and TM4 with AMD3100
      is consistent with the positive charge of bicyclams, which might block HIV-1
      entry by preventing electrostatic interactions between CXCR4 and the HIV-1
      envelope protein gp120. Other features of AMD3100 must account for its high
      antiviral activity, in particular the presence of an aromatic linker between the
      cyclam units. This aromatic group might engage in hydrophobic interactions with
      the Phe-X-Phe motifs of ECL2 or TM4. These results confirm the importance of ECL2
      for the HIV coreceptor activity of CXCR4.

PMID- 9658079
TI  - The cytomegalovirus-encoded chemokine receptor US28 can enhance cell-cell fusion
      mediated by different viral proteins.
AB  - The human cytomegalovirus (CMV) US28 gene encodes a functional CC chemokine
      receptor. However, this activity was observed in cells transfected to express
      US28 and might not correspond to the actual role of the protein in the CMV life
      cycle. Expression of US28 allows human immunodeficiency virus type 1 (HIV-1)
      entry into certain CD4(+) cells and their fusion with cells expressing HIV-1
      envelope (Env) proteins. Such properties were initially reported for the cellular
      chemokine receptors CCR5 and CXCR4, which behave as CD4-associated HIV-1
      coreceptors. We found that coexpression of US28 and either CXCR4 or CCR5 in
      CD4(+) cells resulted in enhanced synctium formation with HIV-1 Env+ cells. This
      positive effect of US28 on cell fusion seems to be distinct from its HIV-1
      coreceptor activity. Indeed, enhancement of cell fusion was also observed when
      US28 was expressed on the HIV-1 Env+ cells instead of an CD4(+) target cells.
      Furthermore, US28 could enhance cell fusion mediated by other viral proteins, in
      particular, the G protein of vesicular stomatitis virus (VSV-G). The HIV-1
      coreceptor and fusion-enhancing activities could be affected by mutations in
      different domains of US28. The fusion-enhancing activity of US28 seems to be cell
      type dependent. Indeed, cells coexpressing VSV-G and US28 fused more efficiently
      with human, simian, or feline target cells, while US28 had no apparent effect on
      fusion with the three mouse or rat cell lines tested. The positive effect of US28
      on cell fusion might therefore require its interaction with a cell-specific
      factor. We discuss a possible role for US28 in the fusion of the CMV envelope
      with target cells and CMV entry.

PMID- 9658080
TI  - Analysis of rotavirus nonstructural protein NSP5 phosphorylation.
AB  - The rotavirus nonstructural phosphoprotein NSP5 is encoded by a gene in RNA
      segment 11. Immunofluorescence analysis of fixed cells showed that NSP5
      polypeptides remained confined to viroplasms even at a late stage when provirions
      migrated from these structures. When NSP5 was expressed in COS-7 cells in the
      absence of other viral proteins, it was uniformly distributed in the cytoplasm.
      Under these conditions, the 26-kDa polypeptide predominated. In the presence of
      the protein phosphatase inhibitor okadaic acid, the highly phosphorylated 28- and
      32- to 35-kDa polypeptides were formed. Also, the fully phosphorylated protein
      had a homogeneous cytoplasmic distribution in transfected cells. In rotavirus
      SA11-infected cells, NSP5 synthesis was detectable at 2 h postinfection. However,
      the newly formed 26-kDa NSP5 was not converted to the 28- to 35-kDa forms until
      approximately 2 h later. Also, the protein kinase activity of isolated NSP5 was
      not detectable until the 28- and 30- to 35-kDa NSP5 forms had been formed. NSP5
      immunoprecipitated from extracts of transfected COS-7 cells was active in
      autophosphorylation in vitro, demonstrating that other viral proteins were not
      required for this function. Treatment of NSP5-expressing cells with
      staurosporine, a broad-range protein kinase inhibitor, had only a limited
      negative effect on the phosphorylation of the viral polypeptide. Staurosporine
      did not inhibit autophosphorylation of NSP5 in vitro. Together, the data support
      the idea that NSP5 has an autophosphorylation activity that is positively
      regulated by addition of phosphate residues at some positions.

PMID- 9658082
TI  - cis Elements required for high-level expression of unspliced Gag-containing
      message in Moloney murine leukemia virus.
AB  - The 441-nucleotide (nt) region (nt 5325 to 5766) around the splice acceptor (SA)
      site (nt 5491) was found to be necessary for high-level expression of gag
      containing unspliced RNA of Moloney murine leukemia virus (M. Oshima, T. Odawara,
      T. Matano, H. Sakahira, K. Kuchino, A. Iwamoto, and H. Yoshikura, J. Virol.
      70:2286-2295, 1996). Detailed genetic dissection of the 441-nt region revealed
      that the 5'-end 64 nt (nt 5325 to 5389) were necessary for high-level expression
      of the unspliced RNA when the spliced RNA was not produced, while the 3'-side 301
      nt (nt 5466 to 5766) containing the SA site were necessary for producing spliced
      RNA. When the spliced RNA was produced, the unspliced RNA could be expressed at a
      high level even when the 5'-end 64 nt were absent. Probably the virus sequence
      ensuring the splicing could produce an RNA structure able to compensate for the
      function of the 5'-end 64-nt region responsible for the expression of the
      unspliced RNA.

PMID- 9658081
TI  - Binding of human immunodeficiency virus type 1 to CD4 and CXCR4 receptors
      differentially regulates expression of inflammatory genes and activates the
      MEK/ERK signaling pathway.
AB  - We have previously shown that binding of human immunodeficiency virus type 1 (HIV
      1) virions to CD4 receptors stimulates association of Lck with Raf-1 and results
      in the activation of Raf-1 kinase in a Ras-independent manner. In the present
      study, we demonstrate that HIV-1 envelope glycoproteins of both T-cell-tropic and
      macrophagetropic strains rapidly activate the ERK/mitogen-activated protein (MAP)
      kinase pathway and the binding of nuclear transcription factors (AP-1, NF-kappaB,
      and C/EBP) and stimulate expression of cytokine and chemokine genes. The
      activation of this signaling pathway requires functional CD4 receptors and is
      independent of binding to CXCR4. Binding of the natural ligand stromal cell
      derived factor 1 (SDF-1) to CXCR4, which inhibits entry of T-cell-tropic HIV-1,
      activates also the ERK/MAP kinase pathway. However, SDF-1 did not affect the CD4
      mediated expression of cytokine and chemokine genes. These results provide firm
      molecular evidence that binding of HIV-1 envelope glycoproteins to CD4 receptor
      initiates a signaling pathway(s) independent of the binding to the chemokine
      receptor that leads to the aberrant expression of inflammatory genes and may
      contribute significantly to HIV-1 replication as well as to deregulation of the
      immune system.

PMID- 9658083
TI  - Intestinal intraepithelial lymphocytes are primed for gamma interferon and MIP
      1beta expression and display antiviral cytotoxic activity despite severe CD4(+) T
      cell depletion in primary simian immunodeficiency virus infection.
AB  - Intraepithelial lymphocytes (IEL) are a critical effector component of the gut
      associated lymphoid tissue (GALT) and play an important role in mucosal immunity
      as well as in the maintenance of the epithelial cell integrity and barrier
      function. The objective of this study was to determine whether simian
      immunodeficiency virus (SIV) infection of rhesus macaques would cause alterations
      in the immunophenotypic profiles of IEL and their mitogen-specific cytokine
      (gamma interferon [IFN-gamma] and MIP-1beta) responses (by flow cytometry) and
      virus-specific cytotoxic T-cell (CTL) activity (by the chromium release assay).
      Virally infected IEL were detected through the entire course of SIV infection by
      in situ hybridization. Severe depletion of CD4(+) single-positive and
      CD4(+)CD8(+) double-positive T cells occurred early in primary SIV infection,
      which was coincident with an increased prevalence of CD8(+) T cells. This was in
      contrast to a gradual depletion of CD4(+) T cells in peripheral blood. The CD8(+)
      IEL were the primary producers of IFN-gamma and MIP-1beta and were found to
      retain their potential to produce both IFN-gamma and MIP-1beta through the entire
      course of SIV infection. SIV-specific CTL activity was detected in primary IEL at
      1, 2, and 4 weeks post-SIV infection. These results demonstrated that IEL may be
      involved in generating antiviral immune responses early in SIV infection and in
      suppressing viral infection thereafter. Alterations in homeostasis in epithelia
      due to severe CD4(+) T-cell depletion accompanied by changes in the cytokine and
      chemokine production by IEL may play a role in the enteropathogenesis of SIV
      infection.

PMID- 9658084
TI  - Human immunodeficiency virus type 1 replication is modulated by host cyclophilin
      A expression levels.
AB  - Human immunodeficiency virus type 1 (HIV-1) Gag and the cellular protein
      cyclophilin A form an essential complex in the virion core: virions produced by
      proviruses encoding Gag mutants with decreased cyclophilin A affinity exhibit
      attenuated infectivity, as do virions produced in the presence of the competitive
      inhibitor cyclosporine. The A224E Gag mutant has no effect on cyclophilin A
      affinity but renders HIV-1 replication cyclosporine resistant in Jurkat T cells.
      In contrast, A224E mutant virus is dead in H9 T cells, although replication is
      rescued by cyclosporine or by expression in cis of a Gag mutant that decreases
      cyclophilin A-affinity. The observation that disruption of the Gag-cyclophilin A
      interaction rescues A224E mutant replication in H9 cells prompted experiments
      which revealed that, relative to Jurkat cells, H9 cells express greater
      quantities of cyclophilin A. The resulting larger quantity of cyclophilin A shown
      to be packaged into virions produced by H9 cells is presumably disruptive to the
      A224E mutant virion core. Further evidence that increased cyclophilin A
      expression in H9 cells is of functional relevance was provided by the finding
      that Gag mutants with decreased cyclophilin A affinity are dead in Jurkat cells
      but capable of replication in H9 cells. Similarly, cyclosporine concentrations
      which inhibit wild-type HIV-1 replication in Jurkat cells stimulate HIV-1
      replication in H9 cells. These results suggest that HIV-1 virion infectivity
      imposes narrow constraints upon cyclophilin A stoichiometry in virions and that
      infectivity is finely tuned by host cyclophilin A expression levels.

PMID- 9658085
TI  - Transfectant influenza A viruses with long deletions in the NS1 protein grow
      efficiently in Vero cells.
AB  - We established a reverse genetics system for the nonstructural (NS) gene segment
      of influenza A virus. This system is based on the use of the temperature
      sensitive (ts) reassortant virus 25A-1. The 25A-1 virus contains the NS gene from
      influenza A/Leningrad/134/57 virus and the remaining gene segments from A/Puerto
      Rico (PR)/8/34 virus. This particular gene constellation was found to be
      responsible for the ts phenotype. For reverse genetics of the NS gene, a plasmid
      derived NS gene from influenza A/PR/8/34 virus was ribonucleoprotein transfected
      into cells that were previously infected with the 25A-1 virus. Two subsequent
      passages of the transfection supernatant at 40 degreesC selected viruses
      containing the transfected NS gene derived from A/PR/8/34 virus. The high
      efficiency of the selection process permitted the rescue of transfectant viruses
      with large deletions of the C-terminal part of the NS1 protein. Viable
      transfectant viruses containing the N-terminal 124, 80, or 38 amino acids of the
      NS1 protein were obtained. Whereas all deletion mutants grew to high titers in
      Vero cells, growth on Madin-Darby canine kidney (MDCK) cells and replication in
      mice decreased with increasing length of the deletions. In Vero cells expression
      levels of viral proteins of the deletion mutants were similar to those of the
      wild type. In contrast, in MDCK cells the level of the M1 protein was
      significantly reduced for the deletion mutants.

PMID- 9658086
TI  - Biochemical analysis of the secreted and virion glycoproteins of Ebola virus.
AB  - The glycoproteins expressed by a Zaire species of Ebola virus were analyzed for
      cleavage, oligomerization, and other structural properties to better define their
      functions. The 50- to 70-kDa secreted and 150-kDa virion/structural glycoproteins
      (SGP and GP, respectively), which share the 295 N-terminal residues, are cleaved
      near the N terminus by signalase. A second cleavage event, occurring in GP at a
      multibasic site (RRTRR downward arrow) that is likely mediated by furin, results
      in two glycoproteins (GP1 and GP2) linked by disulfide bonding. This furin
      cleavage site is present in the same position in the GPs of all Ebola viruses
      (R[R/K]X[R/K]R downward arrow), and one is predicted for Marburg viruses
      (R[R/K]KR downward arrow), although in a different location. Based on the results
      of cross-linking studies, we were able to determine that Ebola virion peplomers
      are composed of trimers of GP1-GP2 heterodimers and that aspects of their
      structure are similar to those of retroviruses, paramyxoviruses, and influenza
      viruses. We also determined that SGP is secreted from infected cells almost
      exclusively in the form of a homodimer that is joined by disulfide bonding.

PMID- 9658087
TI  - Herpes simplex virus type 1 tegument protein VP22 induces the stabilization and
      hyperacetylation of microtubules.
AB  - The role of the herpes simplex virus type 1 tegument protein VP22 during
      infection is as yet undefined. We have previously shown that VP22 has the unusual
      property of efficient intercellular transport, such that the protein spreads from
      single expressing cells into large numbers of surrounding cells. We also noted
      that in cells expressing VP22 by transient transfection, the protein localizes in
      a distinctive cytoplasmic filamentous pattern. Here we show that this pattern
      represents a colocalization between VP22 and cellular microtubules. Moreover, we
      show that VP22 reorganizes microtubules into thick bundles which are easily
      distinguishable from nonbundled microtubules. These bundles are highly resistant
      to microtubule-depolymerizing agents such as nocodazole and incubation at 4
      degreesC, suggesting that VP22 has the capacity to stabilize the microtubule
      network. In addition, we show that the microtubules contained in these bundles
      are modified by acetylation, a marker for microtubule stability. Analysis of
      infected cells by both immunofluorescence and measurement of microtubule
      acetylation further showed that colocalization between VP22 and microtubules, and
      induction of microtubule acetylation, also occurs during infection. Taken
      together, these results suggest that VP22 exhibits the properties of a classical
      microtubule-associated protein (MAP) during both transfection and infection. This
      is the first demonstration of a MAP encoded by an animal virus.

PMID- 9658088
TI  - Brefeldin A inhibits cell-free, de novo synthesis of poliovirus.
AB  - Brefeldin A (BFA), an inhibitor of intracellular vesicle-dependent secretory
      transport, is a potent inhibitor of poliovirus RNA replication in infected cells.
      We have determined that the unknown mechanism of BFA inhibition of replication is
      reproduced in the cell-free poliovirus translation, replication, and
      encapsidation system. Furthermore, we provide evidence suggesting that the
      cellular mechanism targeted by BFA, the GTP-dependent synthesis of secretory
      transport vesicles, may be involved in viral RNA replication in the system via a
      soluble cellular GTP-binding and -hydrolyzing activity. This activity is related
      to the ARF (ADP-ribosylation factor) family of GTP-binding proteins. ARFs are
      required for the formation of several classes of secretory vesicles, and some
      family members are indirectly inactivated by BFA. Peptides that function as
      competitive inhibitors of ARF activity in cell-free transport systems also
      inhibit poliovirus RNA replication, and this inhibitory effect can be countered
      by the addition of exogenous ARF. We suggest that BFA inhibition of replication
      is diagnostic of a requirement for ARF activity in the cell-free system.

PMID- 9658089
TI  - Naturally occurring human immunodeficiency virus type 1 long terminal repeats
      have a frequently observed duplication that binds RBF-2 and represses
      transcription.
AB  - Approximately 38% of human immunodeficiency virus type 1 (HIV-1)-infected
      patients within the Vancouver Lymphadenopathy-AIDS Study have proviruses bearing
      partial 15- to 34-nucleotide duplications upstream of the NF-kappaB binding sites
      within the 5' long terminal repeat (LTR). This most frequent naturally occurring
      length polymorphism (MFNLP) of the HIV-1 5' LTR encompasses potential binding
      sites for several candidate transcription factors, including TCF-1alpha/hLEF, c
      Ets, AP-4, and Ras-responsive binding factor 2 (RBF-2) (M. C. Estable et al., J.
      Virol. 70:4053-4062, 1996). RBF-2 and an apparently related factor, RBF-1, bind
      to at least four cis elements within the LTR which are required for full
      transcriptional responsiveness to protein-tyrosine kinases and v-Ras (B. Bell and
      I. Sadowski, Oncogene 13:2687-2697, 1996). Here we demonstrate that
      representative MFNLPs from two patients specifically bind RBF-2. In both cases,
      deletion of the MFNLP caused elevated LTR-directed transcription in cells
      expressing RBF-2 but not in cells with undetectable RBF-2. RBF-1, but not RBF-2,
      appears to contain the Ets transcription factor family member
      GABPalpha/GABPbeta1. Taken together with the fact that every MFNLP from a
      comparative study of over 500 LTR sequences from 42 patients contains a predicted
      binding site for RBF-2, our data suggest that the MFNLP is selected in vivo
      because it provides a duplicated RBF-2 cis element, which may limit transcription
      in monocytes and activated T cells.

PMID- 9658090
TI  - The second extracellular loop of CXCR4 determines its function as a receptor for
      feline immunodeficiency virus.
AB  - The feline homolog of the alpha-chemokine receptor CXCR4 has recently been shown
      to support cell-cell fusion mediated by CXCR4-dependent strains of human
      immunodeficiency virus (HIV) and strains of feline immunodeficiency virus (FIV)
      that have been selected for growth in the Crandell feline kidney (CrFK) cell
      line. In this report we demonstrate that expression of CXCR4 alone is sufficient
      to render cells from diverse species permissive for fusion with FIV-infected
      cells, suggesting that CXCR4 is the sole receptor for CrFK-tropic strains of FIV,
      analogous to CD4-independent strains of HIV-2. To identify the regions of CXCR4
      involved in fusion mediated by FIV, we screened panels of chimeric CXCR4
      molecules for the ability to support fusion with FIV-infected cells. Human CXCR4
      supported fusion more efficiently than feline CXCR4 and feline/human CXCR4
      chimeras, suggesting that the second and third extracellular loops of human CXCR4
      contain a critical determinant for receptor function. Rat/human CXCR4 chimeras
      suggested that the second extracellular loop contained the principal determinant
      for receptor function; however, chimeras constructed between human CXCR2 and
      CXCR4 revealed that the first and third loops of CXCR4 contribute to the FIV Env
      binding site, as replacement of these domains with the corresponding domains of
      CXCR2 rendered the molecule nonfunctional in fusion assays. Mutation of the DRY
      motif and the C-terminal cytoplasmic tail of CXCR4 did not affect the ability of
      the molecule to support fusion, suggesting that neither signalling via G proteins
      nor receptor internalization was required for fusion mediated by FIV; similarly,
      truncation of the N terminus of CXCR4 did not affect the function of the molecule
      as a receptor for FIV. CXCR4-transfected feline cells were rendered permissive
      for infection with both the CrFK-tropic PET isolate of FIV and the CXCR4
      dependent RF strain of HIV-1, and susceptibility to infection correlated well
      with ability to support fusion. The data suggest that the second extracellular
      loop of CXCR4 is the major determinant of CXCR4 usage by FIV.

PMID- 9658091
TI  - Viral genetic evolution in macaques infected with molecularly cloned simian
      immunodeficiency virus correlates with the extent of persistent viremia.
AB  - Genetic evolution of the simian immunodeficiency virus (SIV) envelope
      glycoprotein was evaluated in a group of six macaques (Macaca nemestrina)
      infected with the molecularly cloned, moderately pathogenic SIVsm62d. The extent
      of envelope evolution was subsequently evaluated within the context of the
      individual pattern of viremia and disease outcome. Two macaques in this cohort
      developed AIDS by 1.5 years postinoculation (progressors), whereas the remaining
      four macaques remained asymptomatic (nonprogressors). Compared with the
      nonprogressor macaques, the two progressor macaques exhibited higher persistent
      plasma viremia, higher homologous neutralizing antibody titers, and more
      extensive mutation and evolution in the V1 region of envelope. Although clearly
      distinct in each of these parameters from the progressors, the four
      nonprogressors exhibited more individual variability with respect to the extent
      of persistent viremia and genetic evolution of the V1 region of envelope. The
      extent of V1 envelope varied from no apparent V1 evolution in a macaque with good
      viral containment to extensive evolution in one macaque with persistent viremia.
      This study underscores the critical role of persistent replication in the genetic
      evolution of SIV.

PMID- 9658092
TI  - In vivo Ty1 reverse transcription can generate replication intermediates with
      untidy ends.
AB  - Ty1 retrotransposition, like retroviral replication, is a complex series of
      events requiring reverse transcription of an RNA intermediate, RNA-primed minus-
      and plus-strand DNA synthesis, multiple strand transfers, and precise cleavages
      of the template and primers by RNase H. In this report, we examine the structure
      of in vivo Ty1 replication intermediates, specifically with regard to the
      behavior of reverse transcriptase upon reaching template ends and to the
      precision with which RNase H might generate these ends. While the expected 3'
      termini were always identified, terminal nontemplated bases were also observed at
      all of the RNA and DNA template ends examined. Nontemplated A residues were most
      common at all 3' ends, although C residues were preferentially added to minus
      strand termini paused at the 5' end of capped Ty1 RNA. In addition, we observed
      that RNase H removal of the tRNA primer and of the polypurine tract was not
      always precise or efficient. Finally, we noted numerous instances of Ty1 reverse
      transcriptase transferring from normal Ty1 template ends to various tRNA
      templates, with continued synthesis to specific modified bases. A similar pattern
      was obtained for Ty2, indicating that template ends offer unique opportunities
      for these two related reverse transcriptases to generate errors.

PMID- 9658093
TI  - Human T-cell leukemia virus type 1 reverse transcriptase (RT) originates from the
      pro and pol open reading frames and requires the presence of RT-RNase H (RH) and
      RT-RH-integrase proteins for its activity.
AB  - The first description of an active form of a recombinant human T-cell leukemia
      virus type 1 (HTLV-1) reverse transcriptase (RT) and subsequent predictions of
      its amino acid sequence and quaternary structure are reported here. By using
      amino acid alignment methods, the NH2 and COOH termini of the RT, RNase H (RH),
      and integrase (IN) domains of the Pol polyprotein were determined. The HTLV-1 RT
      seems to be unique since its NH2 terminus is probably encoded by the pro open
      reading frame (ORF) fused downstream, via a transframe peptide, to the
      polypeptide encoded by the pol ORF. The HTLV-1 Pol amino acid sequence was
      revealed to be highly similar to that of Rous sarcoma virus (RSV), particularly
      at the RT-RH hinge region. These two domains remain linked for RSV; this may also
      be the case for HTLV-1. In light of these results, RT, RT-RH, and RT-RH-IN genes
      were constructed and introduced into His-tagged protein expression vectors. The
      corresponding proteins were synthesized in vitro, and the DNA polymerase
      activities of different protein combinations were tested. Solely the RT-RH-RT-RH
      IN combination was found to have a significant activity level. Velocity
      sedimentation analysis suggested that the HTLV-1 RT-RH and RT-RH-IN monomers are
      likely associated in an oligomeric structure, probably of the alpha3/beta type.

PMID- 9658094
TI  - Involvement of aminopeptidase N (CD13) in infection of human neural cells by
      human coronavirus 229E.
AB  - Attachment to a cell surface receptor can be a major determinant of virus
      tropism. Previous studies have shown that human respiratory coronavirus HCV-229E
      uses human aminopeptidase N (hAPN [CD13]) as its cellular receptor for infection
      of lung fibroblasts. Although human coronaviruses are recognized respiratory
      pathogens, occasional reports have suggested their possible neurotropism. We have
      previously shown that human neural cells, including glial cells in primary
      cultures, are susceptible to human coronavirus infection in vitro (A. Bonavia, N.
      Arbour, V. W. Yong, and P. J. Talbot, J. Virol. 71:800-806, 1997). However, the
      only reported expression of hAPN in the nervous system is at the level of nerve
      synapses. Therefore, we asked whether hAPN is utilized as a cellular receptor for
      infection of these human neural cell lines. Using flow cytometry, we were able to
      show the expression of hAPN on the surfaces of various human neuronal and glial
      cell lines that are susceptible to HCV-229E infection. An hAPN-specific
      monoclonal antibody (WM15), but not control antibody, inhibited the attachment of
      radiolabeled HCV-229E to astrocytic, neuronal, and oligodendrocytic cell lines. A
      correlation between the apparent amount of cell surface hAPN and the level of
      virus attachment was observed. Furthermore, the presence of WM15 inhibited virus
      infection of these cell lines, as detected by indirect immunofluorescence. These
      results indicate that hAPN (CD13) is expressed on neuronal and glial cell lines
      in vitro and serves as the receptor for infection by HCV-229E. This further
      strengthens the neurotropic potential of this human respiratory virus.

PMID- 9658095
TI  - In vivo pathogenesis of a human immunodeficiency virus type 1 reporter virus.
AB  - Our understanding of human immunodeficiency virus type 1 (HIV-1)-induced
      pathogenesis is hampered by the inability to detect HIV-1 gene expression in
      infected viable cells. In this report, we describe two HIV-1 reporter constructs
      that are replication competent and cytopathic in vivo. These constructs contain
      DNA regions of two different lengths that bear the cDNA for the murine heat
      stable antigen in the vpr region of a CXCR4-tropic virus. We used the SCID-hu
      mouse model and these reporter viruses to perform detailed kinetic studies of HIV
      1 infection of human thymocytes in vivo. We document that the CD4(+)/CD8(+)
      thymocytes are the first to express virus and that this subset demonstrates the
      most rapid and extensive HIV-1-induced cell depletion. Following depletion of
      this subset, subsequent virus expression occurs predominantly in phenotypically
      CD4(-) cells, suggesting that CD4 down-regulation occurs in HIV-1-infected
      thymocytes in vivo. These results demonstrate the utility of these HIV-1 reporter
      constructs to monitor HIV pathogenesis in vitro and in vivo.

PMID- 9658096
TI  - Identification of a human immunodeficiency virus type 2 (HIV-2) encapsidation
      determinant and transduction of nondividing human cells by HIV-2-based lentivirus
      vectors.
AB  - Although previous lentivirus vector systems have used human immunodeficiency
      virus type 1 (HIV-1), HIV-2 is less pathogenic in humans and is amenable to
      pathogenicity testing in a primate model. In this study, an HIV-2 molecular clone
      that is infectious but apathogenic in macaques was used to first define cis
      acting regions that can be deleted to prevent HIV-2 genomic encapsidation and
      replication without inhibiting viral gene expression. Lentivirus encapsidation
      determinants are complex and incompletely defined; for HIV-2, some deletions
      between the major 5' splice donor and the gag open reading frame have been shown
      to minimally affect encapsidation and replication. We find that a larger deletion
      (61 to 75 nucleotides) abrogates encapsidation and replication but does not
      diminish mRNA expression. This deletion was incorporated into a replication
      defective, envelope-pseudotyped, three-plasmid HIV-2 lentivirus vector system
      that supplies HIV-2 Gag/Pol and accessory proteins in trans from an HIV-2
      packaging plasmid. The HIV-2 vectors efficiently transduced marker genes into
      human T and monocytoid cell lines and, in contrast to a murine leukemia virus
      based vector, into growth-arrested HeLa cells and terminally differentiated human
      macrophages and NTN2 neurons. Vector DNA could be detected in HIV-2 vector
      transduced nondividing CD34(+) CD38(-) human hematopoietic progenitor cells but
      not in those cells transduced with murine vectors. However, stable integration
      and expression of the reporter gene could not be detected in these hematopoietic
      progenitors, leaving open the question of the accessibility of these cells to
      stable lentivirus transduction.

PMID- 9658097
TI  - Moloney murine leukemia virus envelope protein subunits, gp70 and Pr15E, form a
      stable disulfide-linked complex.
AB  - The nature and stability of the interactions between the gp70 and Pr15E/p15E
      molecules of murine leukemia virus (MLV) have been disputed extensively. To
      resolve this controversy, we have performed quantitative biochemical analyses on
      gp70-Pr15E complexes formed after independent expression of the amphotropic and
      ecotropic Moloney MLV env genes in BHK-21 cells. We found that all cell
      associated gp70 molecules are disulfide linked to Pr15E whereas only a small
      amount of free gp70 is released by the cells. The complexes were resistant to
      treatment with reducing agents in vivo, indicating that the presence and
      stability of the disulfide interaction between gp70 and Pr15E are not dependent
      on the cellular redox state. However, disulfide-bonded Env complexes were
      disrupted in lysates of nonalkylated cells in a time-, temperature-, and pH
      dependent fashion. Disruption seemed not to be caused by a cellular factor but is
      probably due to a thiol-disulfide exchange reaction occurring within the Env
      complex after solubilization. The possibility that alkylating agents induce the
      formation of the intersubunit disulfide linkage was excluded by showing that
      disulfide-linked gp70-Pr15E complexes exist in freshly made lysates of
      nonalkylated cells and that disruption of the complexes can be prevented by
      lowering the pH. Together, these data establish that gp70 and Pr15E form a stable
      disulfide-linked complex in vivo.

PMID- 9658098
TI  - Template-dependent initiation of Sindbis virus RNA replication in vitro.
AB  - Recent insights into the early events in Sindbis virus RNA replication suggest a
      requirement for either the P123 or P23 polyprotein, as well as mature nsP4, the
      RNA-dependent RNA polymerase, for initiation of minus-strand RNA synthesis. Based
      on this observation, we have succeeded in reconstituting an in vitro system for
      template-dependent initiation of SIN RNA replication. Extracts were isolated from
      cells infected with vaccinia virus recombinants expressing various SIN proteins
      and assayed by the addition of exogenous template RNAs. Extracts from cells
      expressing P123C>S, a protease-defective P123 polyprotein, and nsP4 synthesized a
      genome-length minus-sense RNA product. Replicase activity was dependent upon
      addition of exogenous RNA and was specific for alphavirus plus-strand RNA
      templates. RNA synthesis was also obtained by coexpression of nsP1, P23C>S, and
      nsP4. However, extracts from cells expressing nsP4 and P123, a cleavage-competent
      P123 polyprotein, had much less replicase activity. In addition, a P123
      polyprotein containing a mutation in the nsP2 protease which increased the
      efficiency of processing exhibited very little, if any, replicase activity. These
      results provide further evidence that processing of the polyprotein inactivates
      the minus-strand initiation complex. Finally, RNA synthesis was detected when
      soluble nsP4 was added to a membrane fraction containing P123C>S, thus providing
      a functional assay for purification of the nsP4 RNA polymerase.

PMID- 9658099
TI  - Characterization of a live-attenuated retroviral vaccine demonstrates protection
      via immune mechanisms.
AB  - Live-attenuated retroviruses have been shown to be effective retroviral vaccines,
      but currently little is known regarding the mechanisms of protection. In the
      present studies, we used Friend virus as a model to analyze characteristics of a
      live-attenuated vaccine in protection against virus-induced disease. Highly
      susceptible mice were immunized with nonpathogenic Friend murine leukemia helper
      virus (F-MuLV), which replicates poorly in adult mice. Further attenuation of the
      vaccine virus was achieved by crossing the Fv-1 genetic resistance barrier. The
      minimum dose of vaccine virus required to protect 100% of the mice against
      challenge with pathogenic Friend virus complex was determined to be 10(3) focus
      forming units of attenuated virus. Live vaccine virus was necessary for induction
      of immunity, since inactivated F-MuLV did not induce protection. To determine
      whether immune cells mediated protection, spleen cells from vaccinated donor mice
      were adoptively transferred into syngeneic recipients. The results indicated that
      immune mechanisms rather than viral interference mediated protection.

PMID- 9658100
TI  - Critical role for CD4(+) T cells in controlling retrovirus replication and spread
      in persistently infected mice.
AB  - Reactivations of persistent viral infections pose a significant medical problem
      in immunocompromised cancer, transplant, and AIDS patients, yet little is known
      about how persistent viral infections are immunologically controlled. Here we
      describe a mouse model for investigating the role of the immune response in
      controlling a persistent retroviral infection. We demonstrate that, following
      recovery from acute Friend virus infection, a small number of B cells evade
      immunological destruction and harbor persistent virus. In vivo depletions of T
      cell subsets in persistently infected mice revealed a critical role for CD4(+) T
      cells in controlling virus replication, spread to the erythroid lineage, and
      induction of erythroleukemia. The CD4(+) T-cell effect was independent of CD8(+)
      T cells and in some cases was also independent of virus-neutralizing antibody
      responses. Thus, the CD4(+) T cells may have had a direct antiviral effect. These
      results may have relevance for human immunodeficiency virus (HIV) infections
      where loss of CD4(+) T cells is associated with an increase in HIV replication,
      reactivation of persistent viruses, and a high incidence of virus-associated
      cancers.

PMID- 9658101
TI  - Changing the site of initiation of plus-strand DNA synthesis inhibits the
      subsequent template switch during replication of a hepadnavirus.
AB  - Unique to hepadnavirus reverse transcription is the process of primer
      translocation, in which the RNA primer for the initiation of plus-strand DNA
      synthesis is generated at one site on its template, DR1, and is moved to a new
      site, DR2. For duck hepatitis B virus (DHBV), DR2 is located within 50
      nucleotides of the 5' end of the minus-strand DNA template. When the synthesis of
      plus-strand DNA proceeds to the 5' terminus of the minus strand, the 3' end of
      the minus strand becomes the template for DNA synthesis. This switch in templates
      circularizes the nascent genome and is required for the genesis of the relaxed
      circular form of the DNA and the mature capsid. Maturation of the capsid is a
      prerequisite for virus egress. We have analyzed a series of DHBV variants in
      which plus-strand DNA synthesis was initiated from a new position relative to the
      5' end of the template. For these variants, the subsequent circularization was
      inhibited. We found that when the number of nucleotides between the site of
      initiation of plus-strand DNA synthesis and the 5' end of its template was
      restored to 54 nucleotides, circularization was substantially restored. These
      results mean that the process of circularization is influenced by the earlier
      steps in DNA replication. This sensitivity is consistent with the notion that
      this region of the nascent genome is in a dynamic structure that is crucial for
      successful DNA replication.

PMID- 9658102
TI  - Apoptosis induction by the binding of the carboxyl terminus of human
      immunodeficiency virus type 1 gp160 to calmodulin.
AB  - The role of calmodulin (CaM) in apoptosis induced by gp160 of human
      immunodeficiency virus type 1 was investigated with cells undergoing single-cell
      killing. These cells were found to express, under the control of an inducible
      promoter, wild-type gp160 or mutant gp160 devoid of various lengths of the
      carboxyl terminus. Immunoprecipitation accompanied by immunoblotting revealed
      binding of CaM to wild-type gp160 but not to mutant gp160 bearing a carboxyl
      terminus with a deletion spanning more than five amino acid residues. A
      significant coenzyme activity was detected in the CaM bound to gp160 even in the
      presence of a Ca2+ chelater, EGTA. The cells forming this gp160-CaM complex
      exhibited an elevated intracellular Ca2+ level followed by DNA fragmentation,
      which is a hallmark of apoptosis, and finally cell killing, while the cells not
      forming this complex did not show any significant elevation in Ca2+ level or DNA
      fragmentation. These results thus indicated that CaM plays a key role in gp160
      induced apoptosis.

PMID- 9658103
TI  - The disruption of ND10 during herpes simplex virus infection correlates with the
      Vmw110- and proteasome-dependent loss of several PML isoforms.
AB  - The small nuclear structures known as ND10 or PML nuclear bodies have been
      implicated in a variety of cellular processes including response to stress and
      interferons, oncogenesis, and viral infection, but little is known about their
      biochemical properties. Recently, a ubiquitin-specific protease enzyme (named
      HAUSP) and a ubiquitin-homology family protein (PIC1) have been found associated
      with ND10. HAUSP binds strongly to Vmw110, a herpesvirus regulatory protein which
      has the ability to disrupt ND10, while PIC1 was identified as a protein which
      interacts with PML, the prototype ND10 protein. We have investigated the role of
      ubiquitin-related pathways in the mechanism of ND10 disruption by Vmw110 and the
      effect of virus infection on PML stability. The results show that the disruption
      of ND10 during virus infection correlates with the loss of several PML isoforms
      and this process is dependent on active proteasomes. The PML isoforms that are
      most sensitive to virus infection correspond closely to those which have recently
      been identified as being covalently conjugated to PIC1. In addition, a large
      number of PIC1-protein conjugates can be detected following transfection of a
      PIC1 expression plasmid, and many of these are also eliminated in a Vmw110
      dependent manner during virus infection. These observations provide a biochemical
      mechanism to explain the observed effects of Vmw110 on ND10 and suggest a simple
      yet powerful mechanism by which Vmw110 might function during virus infection.

PMID- 9658104
TI  - Role of the transcription start site core region and transcription factor YY1 in
      Rous sarcoma virus long terminal repeat promoter activity.
AB  - The Rous sarcoma virus (RSV) long terminal repeat (LTR) contains a
      transcriptionally potent enhancer and promoter that functions in a variety of
      cell types. Previous studies have identified the viral sequences required for
      enhancer activity, and characterization of these elements has provided insight
      into the mechanism of RSV transcriptional activity. The objective of this study
      was to better define the RSV LTR promoter by examining the transcription start
      site core (TSSC) region. Deletion of the TSSC resulted in complete loss of
      transcriptional activity despite the presence of a functional TATA box,
      suggesting that the TSSC is required for viral expression. Homologies within the
      TSSC to the DNA binding motif of YY1 suggested that it might regulate promoter
      activity. YY1 has been shown to regulate transcription in some cellular genes and
      viral promoters by binding to sites overlapping the transcription start site. Gel
      shift assays using YY1 antibody identified YY1 as one of three complexes that
      bound to the TSSC. Mutation of the YY1 binding site reduced RSV transcriptional
      activity by more than 50%, suggesting that YY1, in addition to other TSSC-binding
      factors, regulates RSV transcription. Furthermore, in vitro transcription assays
      performed with Drosophila embryo extract (devoid of YY1 activity) showed
      decreased levels of RSV transcription, while transient transfection experiments
      overexpressing YY1 demonstrated that YY1 could transactivate the RSV LTR
      approximately 6- to 7-fold. We propose that the TSSC plays a vital role in RSV
      transcription and that this function is partially carried out by the
      transcription factor YY1.

PMID- 9658105
TI  - Involvement of human CRM1 (exportin 1) in the export and multimerization of the
      Rex protein of human T-cell leukemia virus type 1.
AB  - We investigated the role of human CRM1 (hCRM1) (exportin 1) in the function of
      Rex protein encoded by human T-cell leukemia virus type 1. hCRM1 promoted the
      export of Rex protein from the nucleus to the cytoplasm. A Rex protein with a
      mutation in the activation domain, RexM90, lost both the ability to bind to hCRM1
      and the ability to multimerize. The overexpression of hCRM1 complemented the
      functional defects of RexM64, which contains a mutation in the multimerization
      domain of Rex. A dominant-negative mutant of Rex which sequesters cofactors of
      Rex abrogated multimerization as well as the activity of the wild-type Rex
      protein. These two functions were simultaneously restored by the overexpression
      of hCRM1. Taken together, these results suggest that hCRM1 plays important roles
      in the multimerization and export of Rex protein.

PMID- 9658106
TI  - In vivo effects of mutations in woodchuck hepatitis virus enhancer II.
AB  - Woodchuck hepatitis virus (WHV) enhancer II (EnII) is located upstream of the
      major pregenomic RNA promoter and is thought to play an important role in the
      insertional activation of the N-myc2 gene during WHV hepatocarcinogenesis. WHV
      EnII is recognized by at least three host transcription factors: HNF-1, HNF-4,
      and Oct-1. Here, the roles of these EnII-binding factors in viral transcription
      and replication have been further examined. In HepG2 cells transiently
      transfected with a chloramphenicol acetyltransferase (CAT) gene whose expression
      is dependent upon EnII, mutations in either the HNF-1 or the HNF-4 site strongly
      reduced CAT activity, while ablation of the Oct-1 site decreased CAT expression
      only twofold. Mutations in more than one site completely abolished reporter
      expression. These same mutations were also tested in an overlength WHV genome for
      their impact on viral replication and gene expression. In transfected HepG2
      cells, lesions in the HNF-1 site inactivated pregenomic RNA expression and viral
      reverse transcription, with only minimal effects on the expression of other viral
      mRNAs. By contrast, Oct-1 site lesions had no effect on either viral RNA
      synthesis or DNA replication, and HNF-4 site lesions produced a modest reduction
      of pregenomic RNA but had no impact on viral DNA synthesis. Testing of the
      mutants in susceptible woodchucks revealed that, as expected, viruses with
      lesions in the HNF-1 site were nearly noninfectious, while mutants with lesions
      at the Oct-1 site were fully replication competent. HNF-4 site mutants were
      replication competent but may display reduced levels of replication in the intact
      animal host. We conclude that (i) EnII is primarily devoted to the regulation of
      pregenomic RNA in WHV, (ii) HNF-1 is essential for EnII function in vivo, and
      (iii) HNF-4 plays a demonstrable but adjunctive role in EnII function.

PMID- 9658107
TI  - Identification of a cytotoxic T-lymphocyte response to the novel BARF0 protein of
      Epstein-Barr virus: a critical role for antigen expression.
AB  - The Epstein-Barr virus (EBV)-encoded BARF0 open reading frame gene products are
      consistently expressed in EBV-positive Burkitt's lymphoma (BL) cell lines,
      nasopharyngeal carcinoma cell lines, and lymphoblastoid cell lines (LCLs). Here
      we show that the BARF0 sequence includes an HLA A*0201-restricted cytotoxic T
      lymphocyte (CTL) epitope. By using theoretically predicted HLA A2 binding motifs
      and peptide-loaded antigen presentation-deficient T2 cells, polyclonal BARF0
      specific CD8(+) CTLs were isolated from four different healthy EBV-seropositive
      donors but not from two seronegative donors. These CTL lines recognized the
      peptide epitope LLWAARPRL, which was found to be conserved in 33 of 34 virus
      strains originating from Caucasian, African, and Asian individuals. The BARF0
      specific CTL lines could lyse EBV-negative BL cells stably transfected with the
      BARF0 gene but did not kill HLA A2-matched EBV-positive BL cells and LCLs in a
      standard 51Cr release assay. Reverse transcriptase PCR analysis demonstrated that
      these EBV-positive cell lines expressed significantly lower levels of BARF0 mRNA
      than transfected cells. This data indicated that the BARF0 epitope could be
      endogenously processed; however, antigen levels in the target cell were a
      limiting factor for the effective interaction between BARF0-expressing cells and
      CTLs. The limited expression of BARF0 antigen in EBV-infected BL cells and LCLs
      might contribute to the escape of immune recognition from virus-specific CTLs
      present in the host.

PMID- 9658108
TI  - The human homolog of HAVcr-1 codes for a hepatitis A virus cellular receptor.
AB  - The hepatitis A virus cellular receptor 1 (HAVcr-1) cDNA was isolated from a cDNA
      expression library of African green monkey kidney (AGMK) cells by using
      protective monoclonal antibody (MAb) 190/4, which blocks the binding of hepatitis
      A virus (HAV) to AGMK cells. The HAVcr-1 cDNA codes for havcr-1, a 451-amino-acid
      class I integral-membrane mucin-like glycoprotein of unknown natural function. To
      determine the existence of a human homolog(s) of HAVcr-1 (huHAVcr-1), we used
      HAVcr-1-specific primers to amplify cDNAs from human liver and kidney mRNA by
      reverse transcription-PCR. Nucleotide sequence analysis revealed that the
      amplified liver and kidney huHAVcr-1 cDNAs were identical and that they coded for
      a 359-amino-acid glycoprotein, termed huhavcr-1, which was approximately 79%
      identical to havcr-1. The six Cys residues of the extracellular domain of havcr-1
      and its first N-glycosylation site were conserved in huhavcr-1. However, the
      number of hexameric repeats of the mucin-like region was reduced from 27 in havcr
      1 to 13 in huhavcr-1. In addition, 12 C-terminal amino acids in the cytoplasmic
      domain of huhavcr-1 were deleted. Northern blot analysis of poly(A) RNA showed
      that huhavcr-1 is expressed in every organ analyzed, including the liver, small
      intestine, colon, and spleen, and that it is expressed at higher levels in the
      kidney and testis. Although dog cells transfected with the huHAVcr-1 cDNA did not
      express the protective 190/4 epitope, they bound hepatitis A virus (HAV) and
      gained limited susceptibility to HAV infection. Treatment with MAb 190/4 did not
      protect AGMK cell transfectants expressing huhavcr-1 against HAV, suggesting that
      HAV infected these cells via the huhavcr-1 receptor and not the endogenously
      expressed havcr-1, which was blocked by MAb 190/4. Our data demonstrate that
      huhavcr-1 is a binding receptor for HAV and suggest that it is also a functional
      receptor for HAV.

PMID- 9658109
TI  - Compensatory point mutations in the human immunodeficiency virus type 1 Gag
      region that are distal from deletion mutations in the dimerization initiation
      site can restore viral replication.
AB  - The dimerization initiation site (DIS), downstream of the long terminal repeat
      within the human immunodeficiency virus type 1 (HIV-1) genome, can form a stem
      loop structure (SL1) that has been shown to be involved in the packaging of viral
      RNA. In order to further determine the role of this region in the virus life
      cycle, we deleted the 16 nucleotides (nt) at positions +238 to +253 within SL1 to
      generate a construct termed BH10-LD3 and showed that this virus was impaired in
      viral RNA packaging, viral gene expression, and viral replication. Long-term
      culture of these mutated viruses in MT-2 cells, i.e., 18 passages, yielded
      revertant viruses that possessed infectivities similar to that of the wild type.
      Cloning and sequencing showed that these viruses retained the original 16-nt
      deletion but possessed two additional point mutations, which were located within
      the p2 and NC regions of the Gag coding region, respectively, and which were
      therefore named MP2 and MNC. Site-directed mutagenesis studies revealed that both
      of these point mutations were necessary to compensate for the 16-nt deletion in
      BH10-LD3. A construct with both the 16-nt deletion and the MP2 mutation, i.e.,
      LD3-MP2, produced approximately five times more viral protein than BH10-LD3,
      while the MNC mutation, i.e., construct LD3-MNC, reversed the defects in viral
      RNA packaging. We also deleted nt +261 to +274 within the 3' end of SL1 and
      showed that the diminished infectivity of the mutated virus, termed BH10-LD4,
      could also be restored by the MP2 and MNC point mutations. Therefore,
      compensatory mutations within the p2 and NC proteins, distal from deletions
      within the DIS region of the HIV genome, can restore HIV replication, viral gene
      expression, and viral RNA packaging to control levels.

PMID- 9658110
TI  - Protective role of gamma interferon during the recall response to influenza
      virus.
AB  - During secondary immune responses to influenza virus, virus-specific T memory
      cells are a major source of gamma interferon (IFN-gamma). We assessed the
      contribution of IFN-gamma to heterologous protection against the A/WSN/33 (H1N1)
      virus of wild-type and IFN-gamma-/- mice previously immunized with the A/HK/68
      (H3N2) virus. The IFN-gamma-/- mice displayed significantly reduced survival
      rates subsequent to a challenge with various doses of the A/WSN/33 virus. This
      was associated with an impaired ability of the IFN-gamma-/- mice to completely
      clear the pulmonary virus by day 7 after the challenge, although significant
      reduction of the virus titers was noted. However, the IFN-gamma-/- mice developed
      type A influenza virus cross-reactive cytotoxic T lymphocytes (CTLs) similar to
      the wild-type mice, as demonstrated by both cytotoxicity and a limiting-dilution
      assay for the estimation of CTL precursor frequency. The pulmonary recruitment of
      T cells in IFN-gamma-/- mice was not dramatically affected, and the percentage of
      CD4(+) and CD8(+) T cells was similar to that of wild-type mice. The T cells from
      IFN-gamma-/- mice did not display a significant switch toward a Th2 profile.
      Furthermore, the IFN-gamma-/- mice retained the ability to mount significant
      titers of WSN and HK virus-specific hemagglutination-inhibiting antibodies.
      Together, these results are consistent with a protective role of IFN-gamma during
      the heterologous response against influenza virus independently of the generation
      and local recruitment of cross-reactive CTLs.

PMID- 9658111
TI  - Gastrointestinal T lymphocytes retain high potential for cytokine responses but
      have severe CD4(+) T-cell depletion at all stages of simian immunodeficiency
      virus infection compared to peripheral lymphocytes.
AB  - Gastrointestinal complications in human immunodeficiency virus (HIV) infection
      are indicative of impaired intestinal mucosal immune system. We used simian
      immunodeficiency virus (SIV)-infected rhesus macaques as an animal model for HIV
      to determine pathogenic effects of SIV on intestinal T lymphocytes. Intestinal
      CD4(+) T-cell depletion and the potential for cytokine responses were examined
      during SIV infection and compared with results for lymphocytes from lymph nodes
      and blood. Flow cytometric analysis demonstrated severe depletion of CD4(+)CD8(-)
      single-positive T cells and CD4(+)CD8(+) double-positive T cells in intestinal
      lamina propria lymphocytes (LPL) and intraepithelial lymphocytes (IEL) during
      primary SIV infection which persisted through the entire course of SIV infection.
      In contrast, CD4(+) T-cell depletion was gradual in peripheral lymph nodes and
      blood. Flow cytometric analysis of intracellular gamma interferon (IFN-gamma) and
      interleukin-4 (IL-4) production following short-term mitogenic activation
      revealed that LPL retained same or higher capacity for IFN-gamma production in
      all stages of SIV infection compared to uninfected controls, whereas peripheral
      blood mononuclear cells displayed a gradual decline. The CD8(+) T cells were the
      major producers of IFN-gamma. There was no detectable change in the frequency of
      IL-4-producing cells in both LPL and peripheral blood mononuclear cells. Thus,
      severe depletion of CD4(+) LPL and IEL in primary SIV infection accompanied by
      altered cytokine responses may reflect altered T-cell homeostasis in intestinal
      mucosa. This could be a mechanism of SIV-associated enteropathy and viral
      pathogenesis. Dynamic changes in intestinal T lymphocytes were not adequately
      represented in peripheral lymph nodes or blood.

PMID- 9658113
TI  - T-Cell-independent immunoglobulin G responses in vivo are elicited by live-virus
      infection but not by immunization with viral proteins or virus-like particles.
AB  - Immunoglobulin G (IgG) responses to viruses are generally assumed to be T-cell
      dependent (TD). Recently, however, polyomavirus (PyV) infection of T-cell
      deficient (T-cell receptor beta chain [TCR-beta] -/- or TCR-betaxdelta -/-) mice
      was shown to elicit a protective, T-cell-independent (TI) antiviral IgM and IgG
      response. A repetitive, highly organized antigenic structure common to many TI
      antigens is postulated to be important in the induction of antibody responses in
      the absence of helper T cells. To test whether the repetitive structure of viral
      antigens is essential and/or sufficient for the induction of TI antibodies, we
      compared the abilities of three forms of PyV antigens to induce IgM and IgG
      responses in T-cell-deficient mice: soluble capsid antigens (VP1), repetitive
      virus-like particles (VLPs), and live PyV. Immunization with each of the viral
      antigens resulted in IgM production. VLPs and PyV elicited 10-fold-higher IgM
      titers than VP1, indicating that the highly organized, repetitive antigens are
      more efficient in IgM induction. Antigen-specific TI IgG responses, however, were
      detected only in mice infected with live PyV, not in VP1- or VLP-immunized mice.
      These results suggest that the highly organized, repetitive nature of the viral
      antigens is insufficient to account for their ability to elicit TI IgG response
      and that signals generated by live-virus infection may be essential for the
      switch to IgG production in the absence of T cells. Germinal centers were not
      observed in T-cell-deficient PyV-infected mice, indicating that the germinal
      center pathway of B-cell differentiation is TD even in the context of a virus
      infection.

PMID- 9658112
TI  - Steady-state plasma membrane expression of human cytomegalovirus gB is determined
      by the phosphorylation state of Ser900.
AB  - Human cytomegalovirus (HCMV) infection of an astrocytoma cell line (U373) or
      human fibroblast (HF) cells results in a differential cell distribution of the
      major envelope glycoprotein gB (UL55). This 906-amino-acid type I glycoprotein
      contains an extracellular domain with a signal sequence, a transmembrane domain,
      and a 135-amino-acid cytoplasmic tail with a consensus casein kinase II (CKII)
      site located at Ser900. Since phosphorylation of proteins in the secretory
      pathway is an important determinant of intracellular trafficking, the state of gB
      phosphorylation in U373 and HF cells was examined. Analysis of cells expressing
      wild-type gB and gB with site-specific mutations indicated that the glycoprotein
      was equally phosphorylated at a single site, Ser900, in both U373 and HF cells.
      To assess the effect of charge on gB surface expression in U373 cells, Ser900 was
      replaced with an aspartate (Asp) or alanine (Ala) residue to mimic the
      phosphorylated and nonphosphorylated states, respectively. Expression of the Asp
      but not the Ala gB mutation resulted in an increase in the steady-state
      expression of gB at the plasma membrane (PM) in U373 cells. In addition,
      treatment of U373 cells with the phosphatase inhibitor tautomycin resulted in the
      accumulation of gB at the PM. Interestingly, the addition of a charge at Ser900
      trapped gB in a low-level cycling pathway at the PM, preventing trafficking of
      the protein to the trans-Golgi network or other intracellular compartments.
      Therefore, these results suggest that a tautomycin-sensitive phosphatase
      regulates cell-specific PM retrieval of gB to intracellular compartments.

PMID- 9658114
TI  - Dendritic cells transmit human immunodeficiency virus type 1 to monocytes and
      monocyte-derived macrophages.
AB  - Previous studies have shown that human immunodeficiency virus type 1 (HIV-1)
      exploits dendritic cells (DC) to replicate and spread among CD4(+) T cells. To
      explain the predominance of non-syncytium-inducing (NSI) over syncytium-inducing
      (SI) strains during the initial viremia of HIV, we investigated the ability of
      blood monocyte (Mo)-derived DC to transmit HIV-1 to CD4(+) cells of the
      monocytoid lineage. First, we demonstrate that in our system, DC are able to
      transmit NSI strains, but not SI strains, of HIV-1 to fresh blood Mo and to Mo
      derived macrophages (MDM). To establish a productive infection, a 10-fold-lower
      amount of virus was necessary for DC-mediated transmission of HIV-1 to Mo than in
      case of cell-free infection. Second, immature CD83(-) DC (imDC) transmit virus to
      Mo and MDM with higher efficacy compared to mature CD83(+) DC (maDC); this
      finding is in contrast to data previously obtained with CD4(+) T cells. Third,
      maturation from imDC to maDC efficiently silenced expression of beta2-integrins
      CD11b, CD11c, and CD18 by maDC. Moreover, monoclonal antibody against CD18
      inhibited transmission of HIV-1 from imDC to Mo. We propose that the adhesion
      molecules of the CD11/CD18 family, involved in cell-cell interactions of DC with
      the microenvironment, may play a major role in imDC-mediated HIV-1 infection of
      Mo and MDM.

PMID- 9658115
TI  - Comparisons of highly virulent H5N1 influenza A viruses isolated from humans and
      chickens from Hong Kong.
AB  - Genes of an influenza A (H5N1) virus from a human in Hong Kong isolated in May
      1997 were sequenced and found to be all avian-like (K. Subbarao et al., Science
      279:393-395, 1998). Gene sequences of this human isolate were compared to those
      of a highly pathogenic chicken H5N1 influenza virus isolated from Hong Kong in
      April 1997. Sequence comparisons of all eight RNA segments from the two viruses
      show greater than 99% sequence identity between them. However, neither isolate's
      gene sequence was closely (>95% sequence identity) related to any other gene
      sequences found in the GenBank database. Phylogenetic analysis demonstrated that
      the nucleotide sequences of at least four of the eight RNA segments clustered
      with Eurasian origin avian influenza viruses. The hemagglutinin gene phylogenetic
      analysis also included the sequences from an additional three human and two
      chicken H5N1 virus isolates from Hong Kong, and the isolates separated into two
      closely related groups. However, no single amino acid change separated the
      chicken origin and human origin isolates, but they all contained multiple basic
      amino acids at the hemagglutinin cleavage site, which is associated with a highly
      pathogenic phenotype in poultry. In experimental intravenous inoculation studies
      with chickens, all seven viruses were highly pathogenic, killing most birds
      within 24 h. All infected chickens had virtually identical pathologic lesions,
      including moderate to severe diffuse edema and interstitial pneumonitis. Viral
      nucleoprotein was most frequently demonstrated in vascular endothelium,
      macrophages, heterophils, and cardiac myocytes. Asphyxiation from pulmonary edema
      and generalized cardiovascular collapse were the most likely pathogenic
      mechanisms responsible for illness and death. In summary, a small number of
      changes in hemagglutinin gene sequences defined two closely related subgroups,
      with both subgroups having human and chicken members, among the seven viruses
      examined from Hong Kong, and all seven viruses were highly pathogenic in chickens
      and caused similar lesions in experimental inoculations.

PMID- 9658116
TI  - ORF1a-encoded replicase subunits are involved in the membrane association of the
      arterivirus replication complex.
AB  - Among the functions of the replicase of equine arteritis virus (EAV; family
      Arteriviridae, order Nidovirales) are important viral enzyme activities such as
      proteases and the putative RNA polymerase and RNA helicase functions. The
      replicase is expressed in the form of two polyproteins (open reading frame 1a
      [ORF1a] and ORF1ab), which are processed into 12 nonstructural proteins by three
      viral proteases. In immunofluorescence assays, the majority of these cleavage
      products localized to the perinuclear region of the cell. A dense granular and
      vesicular staining was observed, which strongly suggested membrane association.
      By using confocal microscopy and double-label immunofluorescence, the
      distribution of the EAV replicase was shown to overlap with that of PDI, a
      resident protein of the endoplasmic reticulum and intermediate compartment. An in
      situ labeling of nascent viral RNA with bromo-UTP demonstrated that the membrane
      bound complex in which the replicase subunits accumulate is indeed the site of
      viral RNA synthesis. A number of ORF1a-encoded hydrophobic domains were
      postulated to be involved in the membrane association of the arterivirus
      replication complex. By using various biochemical methods (Triton X-114
      extraction, membrane purification, and sodium carbonate treatment), replicase
      subunits containing these domains were shown to behave as integral membrane
      proteins and to be membrane associated in infected cells. Thus, contribution to
      the formation of a membrane-bound scaffold for the viral replication
      transcription complex appears to be an important novel function for the
      arterivirus ORF1a replicase polyprotein.

PMID- 9658117
TI  - Viral ribonucleoprotein complex formation and nucleolar-cytoplasmic
      relocalization of nucleolin in poliovirus-infected cells.
AB  - The poliovirus 3' noncoding region (3'NCR) is involved in the efficient synthesis
      of viral negative-stranded RNA molecules. A strong interaction between a 105-kDa
      host protein and the wild-type 3'NCR, but not with a replication-defective mutant
      3'NCR, was detected. This 105-kDa protein was identified as nucleolin which
      predominantly resides in the nucleolus and has been proposed to function in the
      folding of rRNA precursor molecules. A functional role for nucleolin in viral
      genome amplification was examined in a cell-free extract which has been shown to
      support the assembly of infectious virus from virion RNA. At early times of viral
      gene expression, extracts depleted of nucleolin produced less infectious virus
      than extracts depleted of fibrillarin, another resident of the nucleolus,
      indicating a functional role of nucleolin in the early stages of the viral life
      cycle in this in vitro system. Immunofluorescence analysis of uninfected and
      infected cells showed a nucleocytoplasmic relocalization of nucleolin, but not of
      fibrillarin, in poliovirus-infected cells. Relocalization of nucleolin was not
      simply a consequence of virally induced inhibition of translation or
      transcription, because inhibitors of translation or transcription did not induce
      nucleolar-cytoplasmic relocalization of nucleolin. These findings suggest a novel
      virus-induced mechanism by which certain nucleolar proteins are selectively
      redistributed in infected cells.

PMID- 9658118
TI  - Human thymidine kinase can functionally replace herpes simplex virus type 1
      thymidine kinase for viral replication in mouse sensory ganglia and reactivation
      from latency upon explant.
AB  - Herpes simplex virus type 1 thymidine kinase exhibits a strikingly broad
      substrate specificity. It is capable of phosphorylating deoxythymidine and
      deoxyuridine as does human thymidine kinase, deoxycytidine as does human
      deoxycytidine kinase, the cytosolic kinase whose amino acid sequence it most
      closely resembles, and thymidylate as does human thymidylate kinase. Following
      peripheral inoculation of mice, viral thymidine kinase is ordinarily required for
      viral replication in ganglia and for reactivation from latency following
      ganglionic explant. To determine which activity of the viral kinase is important
      for replication and reactivation in mouse ganglia, recombinant viruses lacking
      viral thymidine kinase but expressing individual human kinases were constructed.
      Each recombinant virus expressed the appropriate kinase activity with early
      kinetics following infection of cultured cells. The virus expressing human
      thymidine kinase exhibited thymidine phosphorylation activity equivalent to
      approximately 5% of that of wild-type virus in a quantitative plaque
      autoradiography assay. Nevertheless, it was competent for ganglionic replication
      and reactivation following corneal inoculation of mice. The virus expressing
      human thymidylate kinase was partially competent for these activities despite
      failing to express detectable thymidine kinase activity. The virus expressing
      human deoxycytidine kinase failed to replicate acutely in neurons or to
      reactivate from latency. Therefore, it appears that low levels of thymidine
      phosphorylation suffice to fulfill the role of the viral enzyme in ganglia and
      that this role can be partially fulfilled by thymidylate kinase activity alone.

PMID- 9658119
TI  - Actinomycin D inhibits human immunodeficiency virus type 1 minus-strand transfer
      in in vitro and endogenous reverse transcriptase assays.
AB  - In this report we demonstrate that human immunodeficiency virus type 1 (HIV-1)
      minus-strand transfer, assayed in vitro and in endogenous reactions, is greatly
      inhibited by actinomycin D. Previously we showed that HIV-1 nucleocapsid (NC)
      protein (a nucleic acid chaperone catalyzing nucleic acid rearrangements which
      lead to more thermodynamically stable conformations) dramatically stimulates HIV
      1 minus-strand transfer by preventing TAR-dependent self-priming from minus
      strand strong-stop DNA [(-) SSDNA]. Despite this potent activity, the addition of
      NC to in vitro reactions with actinomycin D results in only a modest increase in
      the 50% inhibitory concentration (IC50) for the drug. PCR analysis of HIV-1
      endogenous reactions indicates that minus-strand transfer is inhibited by the
      drug with an IC50 similar to that observed when NC is present in the in vitro
      system. Taken together, these results demonstrate that NC cannot overcome the
      inhibitory effect of actinomycin D on minus-strand transfer. Other experiments
      reveal that at actinomycin D concentrations which severely curtail minus-strand
      transfer, neither the synthesis of (-) SSDNA nor RNase H degradation of donor RNA
      is affected; however, the annealing of (-) SSDNA to acceptor RNA is significantly
      reduced. Thus, inhibition of the annealing reaction is responsible for
      actinomycin D-mediated inhibition of strand transfer. Since NC (but not reverse
      transcriptase) is required for efficient annealing, we conclude that actinomycin
      D inhibits minus-strand transfer by blocking the nucleic acid chaperone activity
      of NC. Our findings also suggest that actinomycin D, already approved for
      treatment of certain tumors, might be useful in combination therapy for AIDS.

PMID- 9658120
TI  - The immunogenic glycoprotein gp35-37 of human herpesvirus 8 is encoded by open
      reading frame K8.1.
AB  - Human herpesvirus 8 (HHV-8) is likely to be involved in the pathogenesis of
      Kaposi's sarcoma (KS) and body cavity-based lymphomas (BCBLs). The HHV-8 genome
      is primarily in a latent state in BCBL-derived cell lines like BCBL-1, but lytic
      replication can be induced by phorbol esters (R. Renne, W. Zhang, B. Herndier, M.
      McGrath, N. Abbey, D. Kedes, and D. E. Ganem, Nat. Med. 2:342-346, 1996). A 35-
      to 37-kDa glycoprotein (gp35-37) is the polypeptide most frequently and
      intensively recognized by KS patient sera on Western blots with induced BCBL-1
      cells. Its apparent molecular mass is reduced to 30 kDa by digestion with peptide
      N-glycosidase F. By searching the known HHV-8 genomic sequence for open reading
      frames (ORF) with the potential to encode such a glycoprotein, an additional, HHV
      8-specific reading frame was identified adjacently to ORF K8. This ORF, termed
      K8.1, was found to be transcribed primarily into a spliced mRNA encoding a
      glycoprotein of 228 amino acids. Recombinant K8.1 was regularly recognized by KS
      patient sera in Western blots, and immunoaffinity-purified antibodies to
      recombinant K8.1 reacted with gp35-37. This shows that the immunogenic gp35-37 is
      encoded by HHV-8 reading frame K8.1, which will be a useful tool for studies of
      HHV-8 epidemiology and pathogenesis.

PMID- 9658121
TI  - Complete protein linkage map of poliovirus P3 proteins: interaction of polymerase
      3Dpol with VPg and with genetic variants of 3AB.
AB  - Poliovirus has evolved to maximize its genomic information by producing
      multifunctional viral proteins. The P3 nonstructural proteins harbor various
      activities when paired with different binding partners. These viral polypeptides
      regulate host cell macromolecular synthesis and function as proteinases, as RNA
      binding proteins, or as RNA-dependent RNA polymerase. A cleavage product of the
      P3 region is the genome-linked protein VPg that is essential in the initiation of
      RNA synthesis. We have used an inducible yeast two-hybrid system to analyze
      directly protein-protein interactions among P3 proteins. Sixteen signals of homo-
      or heterodimer interactions have been observed and have been divided into three
      groups. Of interest is the newly discovered affinity of VPg to 3Dpol that
      suggests direct interaction between these molecules in genome replication. A
      battery of 3AB variants (eight clustered-charge-to-alanine changes and five
      single-amino-acid mutations) has been used to map the binding determinants of 3AB
      3AB interaction which were found to differ from the amino acids critical for the
      3AB-3Dpol interaction. The viral proteinase 3Cpro was not found to interact with
      other 3Cpro molecules or with any other P3 polypeptide in yeast cells, a result
      confirmed by glutaraldehyde cross-linking. The weak apparent interaction between
      3AB and 3CDpro scored in the yeast two-hybrid system was in contrast to a strong
      signal by far-Western blotting. The results elucidate, in part, previous results
      of biochemical and genetic analyses. The role of the interactions in RNA
      replication is addressed.

PMID- 9658122
TI  - Fowlpox virus encodes nonessential homologs of cellular alpha-SNAP, PC-1, and an
      orphan human homolog of a secreted nematode protein.
AB  - The genome of fowlpox virus (FWPV), type species of the Avipoxviridae, is
      considerably rearranged compared with that of vaccinia virus (the prototypic
      poxvirus and type species of the Orthopoxviridae) and is 30% larger. It is likely
      that the genome of FWPV contains genes in addition to those found in vaccinia
      virus, probably involved with its replication and survival in the chicken. A
      7,470-bp segment of the FWPV genome has five open reading frames (ORFs), two of
      which encode ankyrin repeat proteins, many examples of which have been found in
      poxviruses. The remaining ORFs encode homologs of cellular genes not reported in
      any other virus. ORF-2 encodes a homolog of the yeast Sec17p and mammalian SNAP
      proteins, crucial to vesicular transport in the exocytic pathway. ORF-3 encodes a
      homolog of an orphan human protein, R31240_2, encoded on 19p13.2. ORF-3 is also
      homologous to three proteins (YLS2, YMV6, and C07B5.5) from the free-living
      nematode Caenorhabditis elegans and to a 43-kDa antigen from the parasitic
      nematode Trichinella spiralis. ORF-5 encodes a homolog of the mammalian plasma
      cell antigen PC-1, a type II glycoprotein with exophosphodiesterase activity. The
      ORFs are present in the virulent precursor, HP1, of the sequenced attenuated
      virus (FP9) and are conserved in other strains of FWPV. They were shown, by
      deletion mutagenesis, to be nonessential to virus replication in tissue culture.
      RNA encoding the viral homolog of PC-1 is expressed strongly early and late in
      infection, but RNAs encoding the homologs of SNAP and R31240_2 are expressed
      weakly and late.

PMID- 9658123
TI  - The high mobility group protein 1 is a coactivator of herpes simplex virus ICP4
      in vitro.
AB  - ICP4 is an activator of herpes simplex virus early and late gene transcription
      during infection and in vitro can efficiently activate the transcription of a
      core promoter template containing only a TATA box and an initiator element. In
      this study, we noted that the extent of activation by ICP4 in vitro was highly
      dependent on the purity of TFIID when recombinant TFIIB, TFIIE, and TFIIF were
      used as sources of these factors. ICP4 efficiently activated transcription with a
      crude TFIID fraction. However, when immunoaffinity-purified TFIID was used in
      place of the less pure TFIID, ICP4 activated transcription to a significantly
      lesser extent. This finding indicated that the crude TFIID fraction may contain
      additional factors that serve as coactivators of ICP4. To test this hypothesis,
      the crude TFIID preparation was further fractionated by gel filtration
      chromatography. The TFIID that eluted from the column lacked the hypothesized
      coactivator activity. A fraction well separated from TFIID contained an activity
      that when added with the TFIID fraction resulted in higher levels of
      transcription in the presence ICP4. Further purification of the coactivator
      containing fraction resulted in the isolation of a single 30-kDa polypeptide
      (p30). p30 was also shown to serve as a coactivator of ICP4 with immunoaffinity
      purified TFIID; however, p30 had no effect on basal transcription. Amino acid
      sequence analysis revealed that p30 was the high mobility group protein 1, which
      has been shown to facilitate the formation of higher-order DNA-protein complexes.

PMID- 9658124
TI  - Multiple enzymatic activities associated with recombinant NS3 protein of
      hepatitis C virus.
AB  - The hepatitis C virus (HCV) nonstructural 3 protein (NS3) contains at least two
      domains associated with multiple enzymatic activities; a serine protease activity
      resides in the N-terminal one-third of the protein, whereas RNA helicase activity
      and RNA-stimulated nucleoside triphosphatase activity are associated with the C
      terminal portion. To study the possible mutual influence of these enzymatic
      activities, a full-length NS3 polypeptide of 67 kDa was expressed as a nonfusion
      protein in Escherichia coli, purified to homogeneity, and shown to retain all
      three enzymatic activities. The protease activity of the full-length NS3 was
      strongly dependent on the activation by a synthetic peptide spanning the central
      hydrophobic core of the NS4A cofactor. Once complexed with the NS4A-derived
      peptide, the full-length NS3 protein and the isolated N-terminal protease domain
      cleaved synthetic peptide substrates with comparable efficiency. We show that, as
      in the case of the isolated protease domain, the protease activity of full-length
      NS3 undergoes inhibition by the N-terminal cleavage products of substrate
      peptides corresponding to the NS4A-NS4B and NS5A-NS5B. We have also characterized
      and quantified the NS3 ATPase, RNA helicase, and RNA-binding activities under
      optimized reaction conditions. Compared with the isolated N-terminal and C
      terminal domains, recombinant full-length NS3 did not show significant
      differences in the three enzymatic activities analyzed in independent in vitro
      assays. We have further explored the possible interdependence of the NS3 N
      terminal and C-terminal domains by analyzing the effect of polynucleotides on the
      modulation of all NS3 enzymatic functions. Our results demonstrated that the
      observed inhibition of the NS3 proteolytic activity by single-stranded RNA is
      mediated by direct interaction with the protease domain rather than with the
      helicase RNA-binding domain.

PMID- 9658125
TI  - A role for herpesvirus saimiri orf14 in transformation and persistent infection.
AB  - The product of open reading frame 14 (orf14) of herpesvirus saimiri (HVS)
      exhibits significant homology with mouse mammary tumor virus superantigen. orf14
      encodes a 50-kDa secreted glycoprotein, as shown previously (Z. Yao, E.
      Maraskovsky, M. K. Spriggs, J. I. Cohen, R. J. Armitage, and M. R. Alderson, J.
      Immunol. 156:3260-3266, 1996). orf14 expressed from recombinant baculovirus
      powerfully induces proliferation of CD4-positive cells originating from several
      different species. To study the role of orf14 in transformation, a mutant form of
      HVS (HVS Deltaorf14) was constructed with a deletion in the orf14 gene. The
      transforming potential of HVS Deltaorf14 was tested in cell culture and in common
      marmosets. Parental HVS subgroup C strain 488 immortalized common marmoset T
      lymphocytes in vitro to interleukin-2-independent growth, while the HVS
      Deltaorf14 mutant did not produce such a growth transformation. In addition, HVS
      Deltaorf14 was nononcogenic in common marmosets. In contrast to other
      nononcogenic HVS mutant viruses which were repeatedly isolated from peripheral
      blood mononuclear cells of infected marmosets for more than 5 months, HVS
      Deltaorf14 did not persist at a high level in vivo. These results demonstrate
      that orf14 of HVS is not required for replication but is required for
      transformation and for high-level persistence in vivo.

PMID- 9658127
TI  - Naturally occurring mutations define a novel function of the hepatitis B virus
      core promoter in core protein expression.
AB  - Functional analysis of naturally occurring hepatitis B virus (HBV) mutations is
      crucial in understanding their impact on disease. We have recently identified two
      mutations in the HBV core promoter of an HBV strain associated with fulminant
      hepatitis leading to highly (15-fold) enhanced replication as a result of
      increased viral encapsidation of pregenomic RNA into the core particles (T. F.
      Baumert et al., J. Clin. Invest. 98:2268-2276, 1996). Functional studies in an
      encapsidation assay had demonstrated that the increase in encapsidation was
      largely independent of pregenomic RNA transcription. In this study, we define the
      molecular mechanism whereby the two core promoter mutations (C to T at nucleotide
      [nt] 1768 and T to A at nt 1770) result in enhanced viral encapsidation and
      replication. The effect of these mutations leading to increased encapsidation is
      mediated through enhanced core protein synthesis (15-fold) by the mutant virus.
      The marked increase in core protein synthesis is largely a result of
      posttranscriptional or translational effect of the mutations because the
      mutations resulted in only a twofold increase in pregenomic RNA transcription. In
      addition, this effect appears to be selective for core expression since reverse
      transcriptase-polymerase expression was increased only twofold. trans
      complementation analyses of HBV replication demonstrated that enhanced
      replication occurred only when the mutations were provided together with the core
      protein in trans, confirming the functional association of the core promoter
      mutations and core protein expression. In addition, the effect of the mutations
      appears to be quantitatively dependent on the strain background to which the
      mutations were introduced. Our study suggests that the HBV core promoter
      regulates core protein expression at both transcriptional and posttranscriptional
      levels.

PMID- 9658126
TI  - Cytoplasmic forms of human T-cell leukemia virus type 1 Tax induce NF-kappaB
      activation.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) Tax targets I-kappaB alpha and I
      kappaB beta for phosphorylation, ubiquitination, and proteasome-mediated
      degradation, causing the nuclear translocation of NF-kappaB/Rel proteins and
      transcription induction of many cellular genes. The mechanism by which a nuclear
      protein such as Tax stimulates I-kappaB phosphorylation and degradation remains
      unclear. Here, we describe two cytoplasmic mutants of Tax, designated TaxDeltaN81
      and TaxDeltaN109, from which the domains important for cyclic AMP response
      element binding factor (CREB) and serum response factor (SRF) binding and nuclear
      transport have been removed. These mutants were unable to trans activate from the
      HTLV-1 21-bp repeats or the serum response element in the c-fos promoter. In
      contrast, they activated NF-kappaB reporters, suggesting that activation of NF
      kappaB by Tax occurs in the cytoplasm. Incorporation of the nuclear localization
      signal (NLS) of the simian virus 40 large T antigen into TaxDeltaN81 and
      TaxDeltaN109 redirected both proteins predominantly to the nucleus yet did not
      restore trans activation via CREB or SRF. The NLS fusion had little effect on
      TaxDeltaN81 but reduced NF-kappaB trans activation by TaxDeltaN109, possibly
      because of its proximity to the NF-kappaB-activating domain of Tax. In contrast
      to wild-type Tax, the cytoplasmic TaxDeltaN mutants are not cytotoxic. Stable
      expression of TaxDeltaN109 in HeLa cells resulted in a significant reduction in
      the intracellular level of I-kappaB alpha, with the constitutive presence of NF
      kappaB in the nucleus and concomitant activation of the NF-kappaB enhancer. These
      results are suggestive of a potential application of the TaxDeltaN109-like
      mutants in targeting I-kappaB degradation and NF-kappaB activation.
      Interestingly, a Tax species with a molecular mass similar to that of
      TaxDeltaN109 was identified in many HTLV-1-transformed T cells, suggesting that
      TaxDeltaN109-like species might play a role in HTLV-1-induced leukemogenesis.

PMID- 9658128
TI  - Priming with tat-deleted caprine arthritis encephalitis virus (CAEV) proviral DNA
      or live virus protects goats from challenge with pathogenic CAEV.
AB  - We previously reported that infection of goats with caprine arthritis
      encephalitis virus (CAEV) tat- proviral DNA or virus results in persistent
      infection, since the animals seroconverted and direct virus isolation from
      cultures of blood-derived macrophages was positive. In this study we wanted to
      determine whether goats injected with CAEV tat- proviral DNA or virus were
      protected against challenge with the pathogenic homologous virus and to
      investigate whether CAEV tat- was still pathogenic. All animals injected with
      CAEV tat- became infected as indicated by seroconversion and virus isolation.
      Challenge at 8 or 9 months postinfection demonstrated protection in four of four
      animals injected with CAEV tat- but did not in three of three mock-inoculated
      challenged goats. Challenge virus was undetectable in the blood macrophages of
      protected animals during a period of 6 or 10 months postchallenge. In two of four
      protected animals, however, we were able to detect the challenge wild-type virus
      by reverse transcriptase PCR on RNA directly extracted from synovial membrane
      cells surrounding the inoculation site. This result suggests that protection was
      achieved without complete sterilizing immunity. Animals injected with CAEV tat-
      and mock challenged developed inflammatory lesions in the joints, although these
      lesions were not as severe as those in CAEV wild-type-injected goats. These
      results confirm the dispensable role of Tat in CAEV replication in vivo for the
      establishment of infection and pathogenesis and demonstrate in another lentivirus
      infection model the efficacy of live attenuated viruses to induce resistance to
      superinfection.

PMID- 9658129
TI  - Sequence requirements for removal of tRNA by an isolated human immunodeficiency
      virus type 1 RNase H domain.
AB  - Retroviral reverse transcriptase-associated RNase H enzymes are responsible for
      degradation of viral RNA, including removal of the tRNA primer after plus-strand
      strong-stop synthesis and cleavage of the polypurine tract primer. These
      activities are required for the complex viral replication and result in
      generation of the long terminal repeats. The human immunodeficiency virus type 1
      (HIV-1) RNase H domain has been expressed independently of the polymerase domain
      and possesses Mn2+-dependent activity with a hexahistidine tag. The isolated
      domain maintains the ability to specifically remove a tRNA primer mimic. In this
      study, the substrate determinants for recognition of the cognate tRNA3Lys are
      defined. Model substrates were constructed which mimic the RNA-DNA hybrid
      obtained from plus-strand strong-stop synthesis. Deletion substrates containing
      only 12, 9, or 6 positions of the tRNA primer were capable of being cleaved by
      the isolated RNase H domain. Mismatch and bromodeoxyuridine mutagenesis analysis
      indicated that positions 2, 3, 4, and 6, when mutated, affected the specificity
      of RNase H activity. Substitution substrates indicated that positions 4 and 6
      within the RNA primer were important for recognition and cleavage by the HIV-1
      isolated RNase H domain. Moloney murine leukemia virus-HIV-1 hybrid substrates
      were constructed which demonstrated that changes to HIV-1 sequences at positions
      4 and 6 were sufficient but not optimal for regaining cleavage by the isolated
      HIV-1 RNase H domain. Optimal site-specific cleavage between the terminal
      ribonucleotide A and ribonucleotide C requires additional sequences beyond the
      first six positions but less than nine.

PMID- 9658130
TI  - Overexpression of an alternatively spliced form of c-Myb results in increases in
      transactivation and transforms avian myelomonoblasts.
AB  - An alternatively spliced form of c-myb exists that encodes an additional 120
      amino acids in chicken and 121 amino acids in human and mouse. These amino acids
      are encoded by an additional exon, termed exon 9A. This exon is not present in v
      myb, and proteins containing these amino acids have never been tested for
      oncogenic transformation. A series of myb constructs was therefore created in
      order to compare the functions of Myb proteins on the basis of their inclusion or
      exclusion of the amino acids encoded by exon 9A (E9A). We found that the presence
      of E9A resulted in a robust increase in transactivation for full-length c-Myb
      (CCC), as well as the singly truncated derivatives dCC and CCd, while doubly
      truncated Myb proteins v-Myb (dVd) and dCd did not exhibit any differences in
      transactivation. The increase in transactivation requires the Myb DNA-binding
      domain. When the leukemic transformation by the Myb proteins was tested, it was
      found that cells transformed by dVd resembled monoblasts, while cells transformed
      by CCC and its derivatives, dCd, dCC, and CCd, resembled myelomonoblasts. Despite
      differences in the morphology of the hematopoietic cells, the cell surface
      phenotypes and cell cycle profiles of transformed cells did not change for each
      pair of Myb proteins in the presence or absence of E9A. Thus, there was no direct
      correlation between the level of transcriptional activation and the strength of
      leukemic transformation.

PMID- 9658131
TI  - p53 protein is a suppressor of papillomavirus DNA amplificational replication.
AB  - p53 protein was able to block human and bovine papillomavirus DNA amplificational
      replication while not interfering with Epstein-Barr virus oriP once-per-cell
      cycle replication. Oligomerization, intact DNA-binding, replication protein A
      binding, and proline-rich domains of the p53 protein were essential for efficient
      inhibition, while the N-terminal transcriptional activation and C-terminal
      regulatory domains were dispensable for the suppressor activity of the p53
      protein. The inhibition of replication was caused neither by the downregulation
      of expression of the E1 and E2 proteins nor by cell cycle block or apoptosis. Our
      data suggest that the intrinsic activity of p53 to suppress amplificational
      replication of the papillomavirus origin may have an important role in the virus
      life cycle and in virus-cell interactions.

PMID- 9658132
TI  - Localization of varicella-zoster virus gene 21 protein in virus-infected cells in
      culture.
AB  - Although four varicella-zoster virus (VZV) genes have been shown to be
      transcribed in latently infected human ganglia, their role in the development and
      maintenance of latency is unknown. To study these VZV transcripts, we decided
      first to localize their expression products in productively infected cells. We
      began with VZV gene 21, whose open reading frame (ORF) is 3,113 bp. We cloned the
      5' and 3' ends and the predicted antigenic segments of the ORF as 1292-, 1280-,
      and 880-bp DNA fragments, respectively, into the prokaryotic expression vector
      pGEX-2T. The three VZV 21 ORFs were expressed as approximately 75-, 73-, and 59
      kDa glutathione S-transferase fusion proteins in Escherichia coli. To prepare
      polyclonal antibodies that would recognize all potential epitopes on the VZV gene
      21 protein, rabbits were inoculated with a mixture of the three fusion proteins,
      and antisera were obtained and affinity purified. Immunohistochemical and
      immunoelectron microscopic analyses using these antibodies revealed VZV ORF 21
      protein in both the nucleus and cytoplasm of VZV-infected cells. When these
      antibodies were applied to purified VZV nucleocapsids, intense staining was seen
      in their central cores.

PMID- 9658133
TI  - Coronavirus particle assembly: primary structure requirements of the membrane
      protein.
AB  - Coronavirus-like particles morphologically similar to normal virions are
      assembled when genes encoding the viral membrane proteins M and E are coexpressed
      in eukaryotic cells. Using this envelope assembly assay, we have studied the
      primary sequence requirements for particle formation of the mouse hepatitis virus
      (MHV) M protein, the major protein of the coronavirion membrane. Our results show
      that each of the different domains of the protein is important. Mutations
      (deletions, insertions, point mutations) in the luminal domain, the transmembrane
      domains, the amphiphilic domain, or the carboxy-terminal domain had effects on
      the assembly of M into enveloped particles. Strikingly, the extreme carboxy
      terminal residue is crucial. Deletion of this single residue abolished particle
      assembly almost completely; most substitutions were strongly inhibitory. Site
      directed mutations in the carboxy terminus of M were also incorporated into the
      MHV genome by targeted recombination. The results supported a critical role for
      this domain of M in viral assembly, although the M carboxy terminus was more
      tolerant of alteration in the complete virion than in virus-like particles,
      likely because of the stabilization of virions by additional intermolecular
      interactions. Interestingly, glycosylation of M appeared not essential for
      assembly. Mutations in the luminal domain that abolished the normal O
      glycosylation of the protein or created an N-glycosylated form had no effect.
      Mutant M proteins unable to form virus-like particles were found to inhibit the
      budding of assembly-competent M in a concentration-dependent manner. However,
      assembly-competent M was able to rescue assembly-incompetent M when the latter
      was present in low amounts. These observations support the existence of
      interactions between M molecules that are thought to be the driving force in
      coronavirus envelope assembly.

PMID- 9658134
TI  - Kinetics of antiviral activity by human immunodeficiency virus type 1-specific
      cytotoxic T lymphocytes (CTL) and rapid selection of CTL escape virus in vitro.
AB  - The antiviral activity of a CD8(+) cytotoxic T-lymphocyte (CTL) clone (TCC108)
      directed against a newly identified HLA-B14-restricted epitope, human
      immunodeficiency virus type 1 (HIV-1) Rev(67-75) SAEPVPLQL, was analyzed with
      respect to its kinetics of target cell lysis and inhibition of HIV-1 production.
      Addition of TCC108 cells or CD8(+) reverse transcriptase-specific CTLs to HLA
      matched CD4(+) T cells at different times after infection with HIV-1 IIIB showed
      that infected cells became susceptible to CTL-mediated lysis before peak virus
      production but after the onset of progeny virus release. When either of these
      CTLs were added to part of the infected cells immediately after infection, p55
      expression and virus production were significantly suppressed. These data support
      a model in which CTLs, apart from exerting cytolytic activity which may prevent
      continued virus release, can interfere with viral protein expression during the
      eclipse phase via noncytolytic mechanisms. TCC108-mediated inhibition of virus
      replication in peripheral blood mononuclear cells caused rapid selection of a
      virus with a mutation (69E-->K) in the Rev(67-75) CTL epitope which abolished
      recognition by TCC108 cells. Taken together, these data suggest that both
      cytolytic and noncytolytic antiviral mechanisms of CTLs can be specifically
      targeted to HIV-1-infected cells.

PMID- 9658135
TI  - CXCR4 is required by a nonprimate lentivirus: heterologous expression of feline
      immunodeficiency virus in human, rodent, and feline cells.
AB  - A heterologous feline immunodeficiency virus (FIV) expression system permitted
      high-level expression of FIV proteins and efficient production of infectious FIV
      in human cells. These results identify the FIV U3 element as the sole restriction
      to the productive phase of replication in nonfeline cells. Heterologous FIV
      expression in a variety of human cell lines resulted in profuse syncytial lysis
      that was FIV env specific, CD4 independent, and restricted to cells that express
      CXCR4, the coreceptor for T-cell-line-adapted strains of human immunodeficiency
      virus. Stable expression of human CXCR4 in CXCR4-negative human and rodent cell
      lines resulted in extensive FIV Env-mediated, CXCR4-dependent cell fusion and
      infection. In feline cells, stable overexpression of human CXCR4 resulted in
      increased FIV infectivity and marked syncytium formation during FIV replication
      or after infection with FIV Env-expressing vectors. The use of CXCR4 is a
      fundamental feature of lentivirus biology independent of CD4 and a shared
      cellular link to infection and cytopathicity for distantly related lentiviruses
      that cause AIDS. Their conserved use implicates chemokine receptors as primordial
      lentivirus receptors.

PMID- 9658137
TI  - Circumvention of immunity to the adenovirus major coat protein hexon.
AB  - Immunity to adenoviruses is an important hurdle to be overcome for successful
      gene therapy. The presence of antibodies to the capsid proteins prevents
      efficacious adenovirus vector administration in vivo. We tested whether immunity
      to a particular serotype of adenovirus (Ad5) may be overcome with a vector that
      encodes the hexon sequences from a different adenovirus serotype (Ad12). We
      successfully constructed an adenovirus vector with a chimeric Ad5-Ad12 hexon
      which was not neutralized by plasma from C57BL/6 mice immunized with Ad5. The
      vector was also capable of transducing the livers of C57BL/6 mice previously
      immunized with Ad5.

PMID- 9658136
TI  - Infectious laryngotracheitis herpesvirus expresses a related pair of unique
      nuclear proteins which are encoded by split genes located at the right end of the
      UL genome region.
AB  - Avian infectious laryngotracheitis virus (ILTV) possesses an alphaherpesvirus
      type D DNA genome of ca. 155 kbp. Completion of our previous sequence analyses
      (W. Fuchs and T. C. Mettenleiter, J. Gen. Virol. 77:2221-2229, 1996) of the right
      end of the unique long (UL) genome region revealed the presence of two adjacent,
      presumably ILTV-specific genes, which were named UL0 and UL[-1] because of their
      location upstream of the conserved UL1 (glycoprotein L) gene. Transcriptional
      analyses showed that both genes are abundantly expressed during the late phase of
      the viral replication cycle and that both mRNAs are spliced by the removal of
      short introns close to their 5' ends. Furthermore, the deduced gene products
      exhibit a moderate but significant homology of 28% to each other. The newly
      identified ILTV genes encode proteins of 63 kDa (UL0) and 73 kDa (UL[-1]), which
      both are predominantly localized in the nuclei of virus infected chicken cells.
      In summary, our results indicate that duplication of a spliced ILTV-specific gene
      encoding a nuclear protein has occurred during evolution of ILTV.

PMID- 9658138
TI  - A new vaccinia virus intermediate transcription factor.
AB  - Transcription of the vaccinia virus genome is mediated by a virus-encoded
      multisubunit DNA-dependent RNA polymerase in conjunction with early-,
      intermediate-, and late-stage-specific factors. Previous studies indicated that
      two virus-encoded proteins (capping enzyme and VITF-1) and one unidentified
      cellular protein (VITF-2) are required for specific transcription of an
      intermediate promoter template in vitro. We have now extensively purified an
      additional virus-induced intermediate transcription factor with a native mass of
      approximately 100 kDa.

PMID- 9658139
TI  - Increased susceptibility of diabetic mice to influenza virus infection:
      compromise of collectin-mediated host defense of the lung by glucose?
AB  - The influence of diabetes on susceptibility to influenza virus infection was
      examined in a mouse model in which RIP-Kb transgenic mice and their nontransgenic
      littermates were used as the diabetic and nondiabetic hosts, respectively.
      Influenza virus A/Phil/82 (H3N2) grew to significantly higher titers in the lungs
      of diabetic than nondiabetic mice. The extent of viral replication in the lungs
      was proportional to blood glucose levels in the mice at the time of infection,
      and the enhanced susceptibility of diabetic mice was reversed with insulin.
      Growth of A/HKx31 (H3N2) virus was also enhanced in diabetic mice, whereas the
      highly virulent strain A/PR/8/34 (H1N1) showed no difference in virus yields in
      diabetic and nondiabetic mice, even with low inocula. A/Phil/82 and A/HKx31 are
      sensitive to neutralization in vitro by the pulmonary collectin surfactant
      protein D (SP-D), whereas A/PR/8/34 is essentially resistant. Glucose is a ligand
      for SP-D, and neutralization of A/Phil/82 virus by SP-D was abolished in the
      presence of glucose at levels commonly found in diabetic mice. These findings
      suggest that in mice, and perhaps in humans, diabetes predisposes to influenza
      virus infection through compromise of collectin-mediated host defense of the lung
      by glucose.

PMID- 9658140
TI  - The probability of in vivo reactivation of herpes simplex virus type 1 increases
      with the number of latently infected neurons in the ganglia.
AB  - The purpose of this study was to define the relationship between herpes simplex
      virus (HSV) latency and in vivo ganglionic reactivation. Groups of mice with
      numbers of latently infected neurons ranging from 1.9 to 24% were generated by
      varying the input titer of wild-type HSV type 1 strain 17syn+. Reactivation of
      the virus in mice from each group was induced by hyperthermic stress. The number
      of animals that exhibited virus reactivation was positively correlated with the
      number of latently infected neurons in the ganglia over the entire range examined
      (r = 0.9852, P < 0. 0001 [Pearson correlation]).

PMID- 9658141
TI  - The papillomavirus E1 protein forms a DNA-dependent hexameric complex with ATPase
      and DNA helicase activities.
AB  - The E1 protein from bovine papillomavirus has site-specific DNA binding activity,
      DNA helicase activity, and DNA-dependent ATPase activity consistent with the
      properties of an initiator protein. Here we have identified and characterized a
      novel oligomeric form of E1 that is associated with the ATPase and DNA helicase
      activities and whose formation is strongly stimulated by single-stranded DNA.
      This oligomeric form corresponds to a hexamer of E1.

PMID- 9658142
TI  - Binding of murine leukemia virus Gag polyproteins to KIF4, a microtubule-based
      motor protein.
AB  - A cDNA clone encoding a cellular protein that interacts with murine leukemia
      virus (MuLV) Gag proteins was isolated from a T-cell lymphoma library. The
      sequence of the clone is identical to the C terminus of a cellular protein, KIF4,
      a microtubule-associated motor protein that belongs to the kinesin superfamily.
      KIF4-MuLV Gag associations have been detected in vitro and in vivo in mammalian
      cells. We suggest that KIF4 could be involved in Gag polyprotein translocation
      from the cytoplasm to the cell membrane.

PMID- 9658143
TI  - Differential expression of Nur77 family members in human T-lymphotropic virus
      type 1-infected cells: transactivation of the TR3/nur77 gene by Tax protein.
AB  - We analyzed the differential expression and regulation of three members of the
      Nur77 transcription factor family by the human T-lymphotropic virus type 1 (HTLV
      1) Tax protein. We have demonstrated that in both HTLV-1-infected cells and Tax
      expressing JPX-9 cells, TR3/nur77 is highly expressed, whereas neither NOR-1 nor
      NOT expression is detectable. Transient transfection analysis further confirmed
      the Tax transactivation of the TR3/nur77 promoter but not the NOR-1 promoter in
      different cell types. Furthermore, expression of a luciferase reporter gene
      driven by the NGFI-B (rat homolog of TR3/Nur77) response element (NBRE) provided
      evidence that Tax-mediated transactivation resulted in the induction of a
      functional protein. Cotransfection assays with the TR3/nur77 promoter sequence or
      the NBRE binding motif together with a series of Tax mutants have shown that Tax
      induced TR3/nur77 expression is mediated by CREB/ATF-related transcription
      factors.

PMID- 9658144
TI  - Recombinant Sindbis viruses expressing a cytotoxic T-lymphocyte epitope of a
      malaria parasite or of influenza virus elicit protection against the
      corresponding pathogen in mice.
AB  - Subcutaneous administration in mice of recombinant Sindbis viruses expressing a
      class I major histocompatibility complex-restricted 9-mer epitope of the
      Plasmodium yoelii circumsporozoite protein or the nucleoprotein of influenza
      virus induces a large epitope-specific CD8(+) T-cell response. This immunization
      also elicits a high degree of protection against infection with malaria or
      influenza A virus.

PMID- 9658145
TI  - Human immunodeficiency virus type 1 genome activation induced by human T-cell
      leukemia virus type 1 Tax protein is through cooperation of NF-kappaB and Tat.
AB  - For productive replication of human immunodeficiency virus type 1 (HIV-1) in host
      cells, the viral genome-encoded transactivator Tat and several cellular
      transcription factors are required for efficient viral gene transcription.
      However, it remains unclear how the viral genome initiates transcription before
      Tat is transcribed or when Tat is at suboptimal levels. Here, we utilized the
      human T-cell leukemia type 1 Tax protein as a molecular tool to investigate the
      mechanism of viral gene transcription that initiates the early phase of infection
      of HIV-1. Tax alone does not significantly increase the activity of HIV-1 long
      terminal repeat (LTR) in T lymphocytes, but it markedly enhanced the replication
      of an infectious HIV-1 provirus with a truncated nef gene. This enhancement is
      preferentially mediated by the cooperation of Tax and Tat which is dependent on
      TAR and duplicated kappaB cis elements of the HIV-1 LTR as well as the NF-kappaB
      activation domain of Tax. Furthermore, phorbol myristate acetate and membrane
      targeted HIV-1 Nef also enhanced the LTR activity in the presence of Tat in the
      TAR- and kappaB cis element-dependent manner. These data suggest that activated
      NF-kappaB can functionally interact with a suboptimal amount of Tat and the HIV-1
      LTR for efficient initiation of viral gene transcription.

PMID- 9658146
TI  - Interleukin-12 p40 mRNA expression in bovine leukemia virus-infected animals:
      increase in alymphocytosis but decrease in persistent lymphocytosis.
AB  - Interleukin-12 (IL-12), a key cytokine in immune regulation, has an important
      role in activating the cell-mediated immune response in infectious diseases.
      Recently, a dichotomy between IL-12 and IL-10 regarding progression of a variety
      diseases has emerged. IL-12 activates type 1 cytokine production and has an
      antagonistic effect on type 2 cytokines. Here, by using quantitative competitive
      PCR, we show that peripheral blood mononuclear cells from bovine leukemia virus
      infected animals in the alymphocytotic stage of disease express an increased
      amount of IL-12 p40 mRNA. In contrast, IL-12 p40 mRNA expression by cells from
      animals with late-stage disease, termed persistent lymphocytosis, was
      significantly decreased compared to that by normal and alymphocytotic animals.
      Interestingly, IL-12 p40 mRNA was also detected in tumor-bearing animals. IL-12
      p40 expression occurred only in monocytes/macrophages, not B or T lymphocytes.
      The present study combined with previous findings suggest that IL-12 in bovine
      leukemia virus-infected animals may regulate production of other cytokines such
      as gamma interferon and IL-10 and the progression of bovine leukosis in animals
      that develop more advanced disease such as a persistent lymphocytosis of B cells
      or B-cell lymphosarcoma.

PMID- 9658147
TI  - Antigenic structure of human respiratory syncytial virus fusion glycoprotein.
AB  - New series of escape mutants of human respiratory syncytial virus were prepared
      with monoclonal antibodies specific for the fusion (F) protein. Sequence changes
      selected in the escape mutants identified two new antigenic sites (V and VI)
      recognized by neutralizing antibodies and a group-specific site (I) in the F1
      chain of the F molecule. The new epitopes, and previously identified antigenic
      sites, were incorporated into a refined prediction of secondary-structure motifs
      to generate a detailed antigenic map of the F glycoprotein.

PMID- 9658148
TI  - Viral determinants of rotavirus pathogenicity in pigs: evidence that the fourth
      gene of a porcine rotavirus confers diarrhea in the homologous host.
AB  - A porcine rotavirus (prv) monoreassortant, S-F4, which carries RNA segment 4 of
      the pig-pathogenic variant prv 4F in the genetic background of the pig
      apathogenic variant prv 4S (G. I. Tauscher and U. Desselberger, J. Virol. 71:853
      857, 1997), was found to be pathogenic in gnotobiotic piglets. This indicates
      that RNA segment 4 of the pig-pathogenic variant prv 4F is a major determinant of
      pathogenicity in its homologous host.

PMID- 9658149
TI  - Apoptosis in feline panleukopenia virus-infected lymphocytes.
AB  - Feline panleukopenia virus (FPLV) was shown to induce apoptosis to feline
      lymphoid cells and to reduce the expression of interleukin-2 receptor alpha on
      the cells. FPLV-induced apoptosis might be a key element in the pathophysiology
      of atrophy of lymphoid tissues associated with feline panleukopenia caused by
      FPLV.

PMID- 9658150
TI  - Maintenance of an intact human immunodeficiency virus type 1 vpr gene following
      mother-to-infant transmission.
AB  - The vpr sequences from six human immunodeficiency virus type 1 (HIV-1)-infected
      mother-infant pairs following perinatal transmission were analyzed. We found that
      153 of the 166 clones analyzed from uncultured peripheral blood mononuclear cell
      DNA samples showed a 92.17% frequency of intact vpr open reading frames. There
      was a low degree of heterogeneity of vpr genes within mothers, within infants,
      and between epidemiologically linked mother-infant pairs. The distances between
      vpr sequences were greater in epidemiologically unlinked individuals than in
      epidemiologically linked mother-infant pairs. Moreover, the infants' sequences
      displayed patterns similar to those seen in their mothers. The functional domains
      essential for Vpr activity, including virion incorporation, nuclear import, and
      cell cycle arrest and differentiation were highly conserved in most of the
      sequences. Phylogenetic analyses of 166 mother-infant pairs and 195 other
      available vpr sequences from HIV databases formed distinct clusters for each
      mother-infant pair and for other vpr sequences and grouped the six mother-infant
      pairs' sequences with subtype B sequences. A high degree of conservation of
      intact and functional vpr supports the notion that vpr plays an important role in
      HIV-1 infection and replication in mother-infant isolates that are involved in
      perinatal transmission.

PMID- 9658151
TI  - Binding of the human immunodeficiency virus type 1 Gag protein to the viral RNA
      encapsidation signal in the yeast three-hybrid system.
AB  - We have used the yeast three-hybrid system (D. J. SenGupta, B. Zhang, B. Kraemer,
      P. Pochart, S. Fields, and M. Wickens, Proc. Natl. Acad. Sci. USA 93:8496-8501,
      1996) to study binding of the human immunodeficiency virus type 1 (HIV-1) Gag
      protein to the HIV-1 RNA encapsidation signal (HIVPsi). Interaction of these
      elements results in the activation of a reporter gene in the yeast Saccharomyces
      cerevisiae. Using this system, we have shown that the HIV-1 Gag protein binds
      specifically to a 139-nucleotide fragment of the HIVPsi signal containing four
      stem-loop structures. Mutations in either the Gag protein or the encapsidation
      signal that have been shown previously to impair this interaction reduced the
      activation of the reporter gene. Interestingly, the nucleocapsid portion of Gag
      retained the RNA binding activity but lost its specificity compared to the full
      length Gag. These results demonstrate the utility of this system and suggest that
      a variety of genetic analyses could be performed to study Gag-encapsidation
      signal interactions.

PMID- 9658152
TI  - Neutralizing antibodies in sera from macaques immunized with attenuated simian
      immunodeficiency virus.
AB  - Infection with attenuated simian immunodeficiency virus (SIV) in rhesus macaques
      has been shown to raise antibodies capable of neutralizing an animal challenge
      stock of primary SIVmac251 in CEMx174 cells that correlate with resistance to
      infection after experimental challenge with this virulent virus (M. S. Wyand, K.
      H. Manson, M. Garcia-Moll, D. C. Montefiori, and R. C. Desrosiers, J. Virol.
      70:3724-3733, 1996). Here we show that these neutralizing antibodies are not
      detected in human and rhesus peripheral blood mononuclear cells (PBMC). In
      addition, neutralization of primary SIVmac251 in human and rhesus PBMC was rarely
      detected with plasma samples from a similar group of animals that had been
      infected either with SIVmac239Deltanef for 1.5 years or with SIVmac239Delta3 for
      3.2 years, although low-level neutralization was detected in CEMx174 cells.
      Potent neutralization was detected in CEMx174 cells when the latter plasma
      samples were assessed with laboratory-adapted SIVmac251. In contrast to primary
      SIVmac251, laboratory-adapted SIVmac251 did not replicate in human and rhesus
      PBMC despite its ability to utilize CCR5, Bonzo/STRL33, and BOB/gpr15 as
      coreceptors for virus entry. These results illustrate the importance of virus
      passage history and the choice of indicator cells for making assessments of
      neutralizing antibodies to lentiviruses such as SIV. They also demonstrate that
      primary SIVmac251 is less sensitive to neutralization in human and rhesus PBMC
      than it is in established cell lines. Results obtained in PBMC did not support a
      role for neutralizing antibodies as a mechanism of protection in animals
      immunized with attenuated SIV and challenged with primary SIVmac251.

PMID- 9658153
TI  - Ilarviruses encode a Cucumovirus-like 2b gene that is absent in other genera
      within the Bromoviridae.
AB  - We found that RNA 2 of the four ilarviruses sequenced to date encodes an
      additional conserved open reading frame (ORF), 2b, that overlaps the 3' end of
      the previously known ORF, 2a. A novel RNA species of 851 nucleotides was found to
      accumulate to high levels in plants infected with spinach latent virus (SpLV).
      Further analysis showed that RNA 4A is a subgenomic RNA of RNA 2 and encodes all
      of ORF 2b. Moreover, a protein species of the size expected for SpLV ORF 2b was
      translated in vitro from the RNA 4A-containing virion RNAs. The data support the
      suggestion that the SpLV 2b protein is translated in vivo. The 2b gene of
      ilarviruses, which is not encoded by alfamoviruses and bromoviruses, shares
      several features with the previously reported cucumovirus 2b gene; however, their
      encoded proteins share no detectable sequence similarities. The evolutionary
      origin of the 2b gene is discussed.

PMID- 9658155
TI  - Microtubule dynamics in mitotic spindle displayed by polarized light microscopy.

PMID- 9658154
TI  - Production of uninfectious human immunodeficiency virus type 1 containing viral
      protein R fused to a single-chain antibody against viral integrase.
AB  - A single-chain antibody (scAb) against human immunodeficiency virus type 1 (HIV
      1) integrase was expressed as a fusion protein of scAb and HIV-1 viral protein R
      (Vpr), together with the HIV-1 genome, in human 293T cells. The expression did
      not affect virion production much but markedly reduced the infectivity of progeny
      virions. The fusion protein was found to be incorporated into the virions. The
      incorporation appears to account for the reduced infectivity.

PMID- 9658156
TI  - Imaging of echinoderm fertilization.

PMID- 9658157
TI  - Self-centering in cytoplasmic fragments of melanophores.

PMID- 9658158
TI  - Golgi membrane dynamics.

PMID- 9658159
TI  - Nuclear and spindle dynamics in budding yeast.

PMID- 9658160
TI  - Formation and turnover of NSF- and SNAP-containing "fusion" complexes occur on
      undocked, clathrin-coated vesicle-derived membranes.
AB  - Specificity of vesicular transport is determined by pair-wise interaction between
      receptors (SNAP receptors or SNAREs) associated with a transport vesicle and its
      target membrane. Two additional factors, N-ethylmaleimide-sensitive fusion
      protein (NSF) and soluble NSF attachment protein (SNAP) are ubiquitous components
      of vesicular transport pathways. However, the precise role they play is not
      known. On the basis that NSF and SNAP can be recruited to preformed SNARE
      complexes, it has been proposed that NSF- and SNAP-containing complexes are
      formed after SNARE-dependent docking of transport vesicles. This would enable
      ATPase-dependent complex disassembly to be coupled directly to membrane fusion.
      Alternatively, binding and release of NSF/SNAP may occur before vesicle docking,
      and perhaps be involved in the activation of SNAREs. To gain more information
      about the point at which so-called 20S complexes form during the transport
      vesicle cycle, we have examined NSF/SNAP/SNARE complex turnover on clathrin
      coated vesicle-derived membranes in situ. This has been achieved under conditions
      in which the extent of membrane docking can be precisely monitored. We
      demonstrate by UV-dependent cross-linking experiments, coupled to laser light
      scattering analysis of membranes, that complexes containing NSF, SNAP, and SNAREs
      will form and dissociate on the surface of undocked transport vesicles.

PMID- 9658161
TI  - A splice-isoform of vesicle-associated membrane protein-1 (VAMP-1) contains a
      mitochondrial targeting signal.
AB  - Screening of a library derived from primary human endothelial cells revealed a
      novel human isoform of vesicle-associated membrane protein-1 (VAMP-1), a protein
      involved in the targeting and/or fusion of transport vesicles to their target
      membrane. We have termed this novel isoform VAMP-1B and designated the previously
      described isoform VAMP-1A. VAMP-1B appears to be an alternatively spliced form of
      VAMP-1. A similar rat splice variant of VAMP-1 (also termed VAMP-1B) has recently
      been reported. Five different cultured cell lines, from different lineages, all
      contained VAMP-1B but little or no detectable VAMP-1A mRNA, as assessed by PCR.
      In contrast, brain mRNA contained VAMP-1A but no VAMP-1B. The VAMP-1B sequence
      encodes a protein identical to VAMP-1A except for the carboxy-terminal five amino
      acids. VAMP-1 is anchored in the vesicle membrane by a carboxy-terminal
      hydrophobic sequence. In VAMP-1A the hydrophobic anchor is followed by a single
      threonine, which is the carboxy-terminal amino acid. In VAMP-1B the predicted
      hydrophobic membrane anchor is shortened by four amino acids, and the hydrophobic
      sequence is immediately followed by three charged amino acids, arginine-arginine
      aspartic acid. Transfection of human endothelial cells with epitope-tagged VAMP
      1B demonstrated that VAMP-1B was targeted to mitochondria whereas VAMP-1A was
      localized to the plasma membrane and endosome-like structures. Analysis of C
      terminal mutations of VAMP-1B demonstrated that mitochondrial targeting depends
      both on the addition of positive charge at the C terminus and a shortened
      hydrophobic membrane anchor. These data suggest that mitochondria may be
      integrated, at least at a mechanistic level, to the vesicular trafficking
      pathways that govern protein movement between other organelles of the cell.

PMID- 9658162
TI  - Tyrosine phosphorylation of selected secretory carrier membrane proteins, SCAMP1
      and SCAMP3, and association with the EGF receptor.
AB  - Secretory carrier membrane proteins (SCAMPs) are ubiquitously expressed proteins
      of post-Golgi vesicles. In the presence of the tyrosine phosphatase inhibitor
      vanadate, or after overexpression in Chinese hamster ovary (CHO) cells, SCAMP1
      and SCAMP3 are phosphorylated selectively on tyrosine residue(s). Phosphorylation
      is reversible after vanadate washout in situ or when isolated SCAMP3 is incubated
      with the recombinant tyrosine phosphatase PTP1B. Vanadate also causes the partial
      accumulation of SCAMP3, but not SCAMP1, in "patches" at or near the cell surface.
      A search for SCAMP kinase activities has shown that SCAMPs 1 and 3, but not
      SCAMP2, are tyrosine phosphorylated in EGF-stimulated murine fibroblasts
      overexpressing the EGF receptor (EGFR). EGF catalyzes the progressive
      phosphorylation of the SCAMPs up to 1 h poststimulation and may enhance
      colocalization of the EGFR and SCAMP3 within the cell interior. EGF also induces
      SCAMP-EGFR association, as detected by coimmunoprecipitation, and phosphorylation
      of SCAMP3 is stimulated by the EGFR in vitro. These results suggest that
      phosphorylation of SCAMPs, either directly or indirectly, may be functionally
      linked to the internalization/down-regulation of the EGFR.

PMID- 9658163
TI  - Expression of the recessive glomerulosclerosis gene Mpv17 regulates MMP-2
      expression in fibroblasts, the kidney, and the inner ear of mice.
AB  - The recessive mouse mutant Mpv17 is characterized by the development of early
      onset glomerulosclerosis, concomitant hypertension, and structural alterations of
      the inner ear. The primary cause of the disease is the loss of function of the
      Mpv17 protein, a peroxisomal gene product involved in reactive oxygen metabolism.
      In our search of a common mediator exerting effects on several aspects of the
      phenotype, we discovered that the absence of the Mpv17 gene product causes a
      strong increase in matrix metalloproteinase 2 (MMP-2) expression. This was seen
      in the kidney and cochlea of Mpv17-negative mice as well as in tissue culture
      cells derived from these animals. When these cells were transfected with the
      human Mpv17 homolog, an inverse causal relationship between Mpv17 and MMP-2
      expression was established. These results indicate that the Mpv17 protein plays a
      crucial role in the regulation of MMP-2 and suggest that enhanced MMP-2
      expression might mediate the mechanisms leading to glomerulosclerosis, inner ear
      disease, and hypertension in this model.

PMID- 9658164
TI  - An atypical sorting determinant in the cytoplasmic domain of P-selectin mediates
      endosomal sorting.
AB  - We previously identified the 11 amino acid C1 region of the cytoplasmic domain of
      P-selectin as essential for an endosomal sorting event that confers rapid
      turnover on P-selectin. The amino acid sequence of this region has no obvious
      similarity to other known sorting motifs. We have analyzed the sequence
      requirements for endosomal sorting by measuring the effects of site-specific
      mutations on the turnover of P-selectin and of the chimeric protein LLP,
      containing the lumenal and transmembrane domains of the low density lipoprotein
      receptor and the cytoplasmic domain of P-selectin. Endosomal sorting activity was
      remarkably tolerant of alanine substitutions within the C1 region. The activity
      was eliminated by alanine substitution of only one amino acid residue, leucine
      768, where substitution with several other large side chains, hydrophobic and
      polar, maintained the sorting activity. The results indicate that the endosomal
      sorting determinant is not structurally related to previously reported sorting
      determinants. Rather, the results suggest that the structure of the sorting
      determinant is dependent on the tertiary structure of the cytoplasmic domain.

PMID- 9658165
TI  - A general RNA-binding protein complex that includes the cytoskeleton-associated
      protein MAP 1A.
AB  - Association of mRNA with the cytoskeleton represents a fundamental aspect of RNA
      physiology likely involved in mRNA transport, anchoring, translation, and
      turnover. We report the initial characterization of a protein complex that binds
      RNA in a sequence-independent but size-dependent manner in vitro. The complex
      includes a approximately 160-kDa protein that is bound directly to mRNA and that
      appears to be either identical or highly related to a approximately 1600-kDa
      protein that binds directly to mRNA in vivo. In addition, the microtubule
      associated protein, MAP 1A, a cytoskeletal associated protein is a component of
      this complex. We suggest that the general attachment of mRNA to the cytoskeleton
      may be mediated, in part, through the formation of this ribonucleoprotein
      complex.

PMID- 9658166
TI  - Complex proteolytic processing acts on Delta, a transmembrane ligand for Notch,
      during Drosophila development.
AB  - Delta functions as a cell nonautonomous membrane-bound ligand that binds to
      Notch, a cell-autonomous receptor, during cell fate specification. Interaction
      between Delta and Notch leads to signal transduction and elicitation of cellular
      responses. During our investigations to further understand the biochemical
      mechanism by which Delta signaling is regulated, we have identified four Delta
      isoforms in Drosophila embryonic and larval extracts. We have demonstrated that
      at least one of the smaller isoforms, Delta S, results from proteolysis. Using
      antibodies to the Delta extracellular and intracellular domains in colocalization
      experiments, we have found that at least three Delta isoforms exist in vivo,
      providing the first evidence that multiple forms of Delta exist during
      development. Finally, we demonstrate that Delta is a transmembrane ligand that
      can be taken up by Notch-expressing Drosophila cultured cells. Cell culture
      experiments imply that full-length Delta is taken up by Notch-expressing cells.
      We present evidence that suggests this uptake occurs by a nonphagocytic
      mechanism.

PMID- 9658167
TI  - Dominant negative alleles of SEC10 reveal distinct domains involved in secretion
      and morphogenesis in yeast.
AB  - The accurate targeting of secretory vesicles to distinct sites on the plasma
      membrane is necessary to achieve polarized growth and to establish specialized
      domains at the surface of eukaryotic cells. Members of a protein complex required
      for exocytosis, the exocyst, have been localized to regions of active secretion
      in the budding yeast Saccharomyces cerevisiae where they may function to specify
      sites on the plasma membrane for vesicle docking and fusion. In this study we
      have addressed the function of one member of the exocyst complex, Sec10p. We have
      identified two functional domains of Sec10p that act in a dominant-negative
      manner to inhibit cell growth upon overexpression. Phenotypic and biochemical
      analysis of the dominant-negative mutants points to a bifunctional role for
      Sec10p. One domain, consisting of the amino-terminal two-thirds of Sec10p
      directly interacts with Sec15p, another exocyst component. Overexpression of this
      domain displaces the full-length Sec10 from the exocyst complex, resulting in a
      block in exocytosis and an accumulation of secretory vesicles. The carboxy
      terminal domain of Sec10p does not interact with other members of the exocyst
      complex and expression of this domain does not cause a secretory defect. Rather,
      this mutant results in the formation of elongated cells, suggesting that the
      second domain of Sec10p is required for morphogenesis, perhaps regulating the
      reorientation of the secretory pathway from the tip of the emerging daughter cell
      toward the mother-daughter connection during cell cycle progression.

PMID- 9658168
TI  - The yeast dynactin complex is involved in partitioning the mitotic spindle
      between mother and daughter cells during anaphase B.
AB  - Although vertebrate cytoplasmic dynein can move to the minus ends of microtubules
      in vitro, its ability to translocate purified vesicles on microtubules depends on
      the presence of an accessory complex known as dynactin. We have cloned and
      characterized a novel gene, NIP100, which encodes the yeast homologue of the
      vertebrate dynactin complex protein p150(glued). Like strains lacking the
      cytoplasmic dynein heavy chain Dyn1p or the centractin homologue Act5p,
      nip100Delta strains are viable but undergo a significant number of failed mitoses
      in which the mitotic spindle does not properly partition into the daughter cell.
      Analysis of spindle dynamics by time-lapse digital microscopy indicates that the
      precise role of Nip100p during anaphase is to promote the translocation of the
      partially elongated mitotic spindle through the bud neck. Consistent with the
      presence of a true dynactin complex in yeast, Nip100p exists in a stable complex
      with Act5p as well as Jnm1p, another protein required for proper spindle
      partitioning during anaphase. Moreover, genetic depletion experiments indicate
      that the binding of Nip100p to Act5p is dependent on the presence of Jnm1p.
      Finally, we find that a fusion of Nip100p to the green fluorescent protein
      localizes to the spindle poles throughout the cell cycle. Taken together, these
      results suggest that the yeast dynactin complex and cytoplasmic dynein together
      define a physiological pathway that is responsible for spindle translocation late
      in anaphase.

PMID- 9658169
TI  - Identification of novel temperature-sensitive lethal alleles in essential beta
      tubulin and nonessential alpha 2-tubulin genes as fission yeast polarity mutants.
AB  - We have screened for temperature-sensitive (ts) fission yeast mutants with
      altered polarity (alp1-15). Genetic analysis indicates that alp2 is allelic to
      atb2 (one of two alpha-tubulin genes) and alp12 to nda3 (the single beta-tubulin
      gene). atb2(+) is nonessential, and the ts atb2 mutations we have isolated are
      dominant as expected. We sequenced two alleles of ts atb2 and one allele of ts
      nda3. In the ts atb2 mutants, the mutated residues (G246D and C356Y) are found at
      the longitudinal interface between alpha/beta-heterodimers, whereas in ts nda3
      the mutated residue (Y422H) is situated in the domain located on the outer
      surface of the microtubule. The ts nda3 mutant is highly sensitive to altered
      gene dosage of atb2(+); overexpression of atb2(+) lowers the restrictive
      temperature, and, conversely, deletion rescues ts. Phenotypic analysis shows that
      contrary to undergoing mitotic arrest with high viability via the spindle
      assembly checkpoint as expected, ts nda3 mutants execute cytokinesis and
      septation and lose viability. Therefore, it appears that the ts nda3 mutant
      becomes temperature lethal because of irreversible progression through the cell
      cycle in the absence of activating the spindle assembly checkpoint pathway.

PMID- 9658170
TI  - Localization of autocrine motility factor receptor to caveolae and clathrin
      independent internalization of its ligand to smooth endoplasmic reticulum.
AB  - Autocrine motility factor receptor (AMF-R) is a cell surface receptor that is
      also localized to a smooth subdomain of the endoplasmic reticulum, the AMF-R
      tubule. By postembedding immunoelectron microscopy, AMF-R concentrates within
      smooth plasmalemmal vesicles or caveolae in both NIH-3T3 fibroblasts and HeLa
      cells. By confocal microscopy, cell surface AMF-R labeled by the addition of anti
      AMF-R antibody to viable cells at 4 degreesC exhibits partial colocalization with
      caveolin, confirming the localization of cell surface AMF-R to caveolae. Labeling
      of cell surface AMF-R by either anti-AMF-R antibody or biotinylated AMF (bAMF)
      exhibits extensive colocalization and after a pulse of 1-2 h at 37 degreesC, bAMF
      accumulates in densely labeled perinuclear structures as well as fainter tubular
      structures that colocalize with AMF-R tubules. After a subsequent 2- to 4-h
      chase, bAMF is localized predominantly to AMF-R tubules. Cytoplasmic
      acidification, blocking clathrin-mediated endocytosis, results in the essentially
      exclusive distribution of internalized bAMF to AMF-R tubules. By confocal
      microscopy, the tubular structures labeled by internalized bAMF show complete
      colocalization with AMF-R tubules. bAMF internalized in the presence of a 10-fold
      excess of unlabeled AMF labels perinuclear punctate structures, which are
      therefore the product of fluid phase endocytosis, but does not label AMF-R
      tubules, demonstrating that bAMF targeting to AMF-R tubules occurs via a receptor
      mediated pathway. By electron microscopy, bAMF internalized for 10 min is located
      to cell surface caveolae and after 30 min is present within smooth and rough
      endoplasmic reticulum tubules. AMF-R is therefore internalized via a receptor
      mediated clathrin-independent pathway to smooth ER. The steady state localization
      of AMF-R to caveolae implicates these cell surface invaginations in AMF-R
      endocytosis.

PMID- 9658171
TI  - Role of tyrosine phosphorylation in ligand-induced regulation of transcytosis of
      the polymeric Ig receptor.
AB  - The polymeric Ig receptor (pIgR) transcytoses its ligand, dimeric IgA (dIgA),
      from the basolateral to the apical surface of epithelial cells. Although the pIgR
      is constitutively transcytosed in the absence of ligand, binding of dIgA
      stimulates transcytosis of the pIgR. We recently reported that dIgA binding to
      the pIgR induces translocation of protein kinase C, production of inositol
      triphosphate, and elevation of intracellular free calcium. We now report that
      dIgA binding causes rapid, transient tyrosine phosphorylation of several
      proteins, including phosphatidyl inositol-specific phospholipase C-gammal.
      Protein tyrosine kinase inhibitors or deletion of the last 30 amino acids of pIgR
      cytoplasmic tail prevents IgA-stimulated protein tyrosine kinase activation,
      tyrosine phosphorylation of phospholipase C-gammal, production of inositol
      triphosphate, and the stimulation of transcytosis by dIgA. Analysis of pIgR
      deletion mutants reveals that the same discrete portion of the cytoplasmic
      domain, residues 727-736 (but not the Tyr734), controls both the ability of pIgR
      to cause dIgA-induced tyrosine phosphorylation of the phospholipase C-gammal and
      to undergo dIgA-stimulated transcytosis. In addition, dIgA transcytosis can be
      strongly stimulated by mimicking phospholipase C-gammal activation. In
      combination with our previous results, we conclude that the protein tyrosine
      kinase(s) and phospholipase C-gammal that are activated upon dIgA binding to the
      pIgR control dIgA-stimulated pIgR transcytosis.

PMID- 9658172
TI  - Serine and threonine phosphorylation of the paxillin LIM domains regulates
      paxillin focal adhesion localization and cell adhesion to fibronectin.
AB  - We have previously shown that the LIM domains of paxillin operate as the focal
      adhesion (FA)-targeting motif of this protein. In the current study, we have
      identified the capacity of paxillin LIM2 and LIM3 to serve as binding sites for,
      and substrates of serine/threonine kinases. The activities of the LIM2- and LIM3
      associated kinases were stimulated after adhesion of CHO.K1 cells to fibronectin;
      consequently, a role for LIM domain phosphorylation in regulating the subcellular
      localization of paxillin after adhesion to fibronectin was investigated. An avian
      paxillin-CHO.K1 model system was used to explore the role of paxillin
      phosphorylation in paxillin localization to FAs. We found that mutations of
      paxillin that mimicked LIM domain phosphorylation accelerated fibronectin-induced
      localization of paxillin to focal contacts. Further, blocking phosphorylation of
      the LIM domains reduced cell adhesion to fibronectin, whereas constitutive LIM
      domain phosphorylation significantly increased the capacity of cells to adhere to
      fibronectin. The potentiation of FA targeting and cell adhesion to fibronectin
      was specific to LIM domain phosphorylation as mutation of the amino-terminal
      tyrosine and serine residues of paxillin that are phosphorylated in response to
      fibronectin adhesion had no effect on the rate of FA localization or cell
      adhesion. This represents the first demonstration of the regulation of protein
      localization through LIM domain phosphorylation and suggests a novel mechanism of
      regulating LIM domain function. Additionally, these results provide the first
      evidence that paxillin contributes to "inside-out" integrin-mediated signal
      transduction.

PMID- 9658173
TI  - Regulation of the cyclin B degradation system by an inhibitor of mitotic
      proteolysis.
AB  - The initiation of anaphase and exit from mitosis depend on the anaphase-promoting
      complex (APC), which mediates the ubiquitin-dependent proteolysis of anaphase
      inhibiting proteins and mitotic cyclins. We have analyzed whether protein
      phosphatases are required for mitotic APC activation. In Xenopus egg extracts APC
      activation occurs normally in the presence of protein phosphatase 1 inhibitors,
      suggesting that the anaphase defects caused by protein phosphatase 1 mutation in
      several organisms are not due to a failure to activate the APC. Contrary to this,
      the initiation of mitotic cyclin B proteolysis is prevented by inhibitors of
      protein phosphatase 2A such as okadaic acid. Okadaic acid induces an activity
      that inhibits cyclin B ubiquitination. We refer to this activity as inhibitor of
      mitotic proteolysis because it also prevents the degradation of other APC
      substrates. A similar activity exists in extracts of Xenopus eggs that are
      arrested at the second meiotic metaphase by the cytostatic factor activity of the
      protein kinase mos. In Xenopus eggs, the initiation of anaphase II may therefore
      be prevented by an inhibitor of APC-dependent ubiquitination.

PMID- 9658174
TI  - Multiple domains of fission yeast Cdc19p (MCM2) are required for its association
      with the core MCM complex.
AB  - The members of the MCM protein family are essential eukaryotic DNA replication
      factors that form a six-member protein complex. In this study, we use antibodies
      to four MCM proteins to investigate the structure of and requirements for the
      formation of fission yeast MCM complexes in vivo, with particular regard to
      Cdc19p (MCM2). Gel filtration analysis shows that the MCM protein complexes are
      unstable and can be broken down to subcomplexes. Using coimmunoprecipitation, we
      find that Mis5p (MCM6) and Cdc21p (MCM4) are tightly associated with one another
      in a core complex with which Cdc19p loosely associates. Assembly of Cdc19p with
      the core depends upon Cdc21p. Interestingly, there is no obvious change in Cdc19p
      containing MCM complexes through the cell cycle. Using a panel of Cdc19p mutants,
      we find that multiple domains of Cdc19p are required for MCM binding. These
      studies indicate that MCM complexes in fission yeast have distinct substructures,
      which may be relevant for function.

PMID- 9658175
TI  - Katanin is responsible for the M-phase microtubule-severing activity in Xenopus
      eggs.
AB  - Microtubules are dynamic structures whose proper rearrangement during the cell
      cycle is essential for the positioning of membranes during interphase and for
      chromosome segregation during mitosis. The previous discovery of a cyclin B/cdc2
      activated microtubule-severing activity in M-phase Xenopus egg extracts suggested
      that a microtubule-severing protein might play an important role in cell cycle
      dependent changes in microtubule dynamics and organization. However, the
      isolation of three different microtubule-severing proteins, p56, EF1alpha, and
      katanin, has only confused the issue because none of these proteins is directly
      activated by cyclin B/cdc2. Here we use immunodepletion with antibodies specific
      for a vertebrate katanin homologue to demonstrate that katanin is responsible for
      the majority of M-phase severing activity in Xenopus eggs. This result suggests
      that katanin is responsible for changes in microtubules occurring at mitosis.
      Immunofluorescence analysis demonstrated that katanin is concentrated at a
      microtubule-dependent structure at mitotic spindle poles in Xenopus A6 cells and
      in human fibroblasts, suggesting a specific role in microtubule disassembly at
      spindle poles. Surprisingly, katanin was also found in adult mouse brain,
      indicating that katanin may have other functions distinct from its mitotic role.

PMID- 9658176
TI  - Activation of Rac and Cdc42 by integrins mediates cell spreading.
AB  - Adhesion to ECM is required for many cell functions including cytoskeletal
      organization, migration, and proliferation. We observed that when cells first
      adhere to extracellular matrix, they spread rapidly by extending filopodia-like
      projections and lamellipodia. These structures are similar to the Rac- and Cdc42
      dependent structures observed in growth factor-stimulated cells. We therefore
      investigated the involvement of Rac and Cdc42 in adhesion and spreading on the
      ECM protein fibronectin. We found that integrin-dependent adhesion led to the
      rapid activation of p21-activated kinase, a downstream effector of Cdc42 and Rac,
      suggesting that integrins activate at least one of these GTPases. Dominant
      negative mutants of Rac and Cdc42 inhibit cell spreading in such a way as to
      suggest that integrins activate Cdc42, which leads to the subsequent activation
      of Rac; both GTPases then contribute to cell spreading. These results demonstrate
      that initial integrin-dependent activation of Rac and Cdc42 mediates cell
      spreading.

PMID- 9658177
TI  - Multiple functions for actin during filamentous growth of Saccharomyces
      cerevisiae.
AB  - Saccharomyces cerevisiae is dimorphic and switches from a yeast form to a
      pseudohyphal (PH) form when starved for nitrogen. PH cells are elongated, bud in
      a unipolar manner, and invade the agar substrate. We assessed the requirements
      for actin in mediating the dramatic morphogenetic events that accompany the
      transition to PH growth. Twelve "alanine scan" alleles of the single yeast actin
      gene (ACT1) were tested for effects on filamentation, unipolar budding, agar
      invasion, and cell elongation. Some act1 mutations affect all phenotypes, whereas
      others affect only one or two aspects of PH growth. Tests of intragenic
      complementation among specific act1 mutations support the phenotypic evidence for
      multiple actin functions in filamentous growth. We present evidence that
      interaction between actin and the actin-binding protein fimbrin is important for
      PH growth and suggest that association of different actin-binding proteins with
      actin mediates the multiple functions of actin in filamentous growth.
      Furthermore, characterization of cytoskeletal structure in wild type and
      act1/act1 mutants indicates that PH cell morphogenesis requires the maintenance
      of a highly polarized actin cytoskeleton. Collectively, this work demonstrates
      that actin plays a central role in fungal dimorphism.

PMID- 9658178
TI  - RhoA GTPase and serum response factor control selectively the expression of MyoD
      without affecting Myf5 in mouse myoblasts.
AB  - MyoD and Myf5 belong to the family of basic helix-loop-helix transcription
      factors that are key operators in skeletal muscle differentiation. MyoD and Myf5
      genes are selectively activated during development in a time and region-specific
      manner and in response to different stimuli. However, molecules that specifically
      regulate the expression of these two genes and the pathways involved remain to be
      determined. We have recently shown that the serum response factor (SRF), a
      transcription factor involved in activation of both mitogenic response and muscle
      differentiation, is required for MyoD gene expression. We have investigated here
      whether SRF is also involved in the control of Myf5 gene expression, and the
      potential role of upstream regulators of SRF activity, the Rho family G-proteins
      including Rho, Rac, and CDC42, in the regulation of MyoD and Myf5. We show that
      inactivation of SRF does not alter Myf5 gene expression, whereas it causes a
      rapid extinction of MyoD gene expression. Furthermore, we show that RhoA, but not
      Rac or CDC42, is also required for the expression of MyoD. Indeed, blocking the
      activity of G-proteins using the general inhibitor lovastatin, or more specific
      antagonists of Rho proteins such as C3-transferase or dominant negative RhoA
      protein, resulted in a dramatic decrease of MyoD protein levels and promoter
      activity without any effects on Myf5 expression. We further show that RhoA
      dependent transcriptional activation required functional SRF in C2 muscle cells.
      These data illustrate that MyoD and Myf5 are regulated by different upstream
      activation pathways in which MyoD expression is specifically modulated by a
      RhoA/SRF signaling cascade. In addition, our results establish the first link
      between RhoA protein activity and the expression of a key muscle regulator.

PMID- 9658179
TI  - Osteoblastic responses to TGF-beta during bone remodeling.
AB  - Bone remodeling depends on the spatial and temporal coupling of bone formation by
      osteoblasts and bone resorption by osteoclasts; however, the molecular basis of
      these inductive interactions is unknown. We have previously shown that
      osteoblastic overexpression of TGF-beta2 in transgenic mice deregulates bone
      remodeling and leads to an age-dependent loss of bone mass that resembles high
      turnover osteoporosis in humans. This phenotype implicates TGF-beta2 as a
      physiological regulator of bone remodeling and raises the question of how this
      single secreted factor regulates the functions of osteoblasts and osteoclasts and
      coordinates their opposing activities in vivo. To gain insight into the
      physiological role of TGF-beta in bone remodeling, we have now characterized the
      responses of osteoblasts to TGF-beta in these transgenic mice. We took advantage
      of the ability of alendronate to specifically inhibit bone resorption, the lack
      of osteoclast activity in c-fos-/- mice, and a new transgenic mouse line that
      expresses a dominant-negative form of the type II TGF-beta receptor in
      osteoblasts. Our results show that TGF-beta directly increases the steady-state
      rate of osteoblastic differentiation from osteoprogenitor cell to terminally
      differentiated osteocyte and thereby increases the final density of osteocytes
      embedded within bone matrix. Mice overexpressing TGF-beta2 also have increased
      rates of bone matrix formation; however, this activity does not result from a
      direct effect of TGF-beta on osteoblasts, but is more likely a homeostatic
      response to the increase in bone resorption caused by TGF-beta. Lastly, we find
      that osteoclastic activity contributes to the TGF-beta-induced increase in
      osteoblast differentiation at sites of bone resorption. These results suggest
      that TGF-beta is a physiological regulator of osteoblast differentiation and acts
      as a central component of the coupling of bone formation to resorption during
      bone remodeling.

PMID- 9658180
TI  - Isolation and contraction of the stress fiber.
AB  - Stress fibers were isolated from cultured human foreskin fibroblasts and bovine
      endothelial cells, and their contraction was demonstrated in vitro. Cells in
      culture dishes were first treated with a low-ionic-strength extraction solution
      and then further extracted using detergents. With gentle washes by pipetting, the
      nucleus and the apical part of cells were removed. The material on the culture
      dish was scraped, and the freed material was forced through a hypodermic needle
      and fractionated by sucrose gradient centrifugation. Isolated, free-floating
      stress fibers stained brightly with fluorescently labeled phalloidin. When
      stained with anti-alpha-actinin or anti-myosin, isolated stress fibers showed
      banded staining patterns. By electron microscopy, they consisted of bundles of
      microfilaments, and electron-dense areas were associated with them in a
      semiperiodic manner. By negative staining, isolated stress fibers often exhibited
      gentle twisting of microfilament bundles. Focal adhesion-associated proteins were
      also detected in the isolated stress fiber by both immunocytochemical and
      biochemical means. In the presence of Mg-ATP, isolated stress fibers shortened,
      on the average, to 23% of the initial length. The maximum velocity of shortening
      was several micrometers per second. Polystyrene beads on shortening isolated
      stress fibers rotated, indicating spiral contraction of stress fibers. Myosin
      regulatory light chain phosphorylation was detected in contracting stress fibers,
      and a myosin light chain kinase inhibitor, KT5926, inhibited isolated stress
      fiber contraction. Our study demonstrates that stress fibers can be isolated with
      no apparent loss of morphological features and that they are truly contractile
      organelle.

PMID- 9658182
TI  - Editorial 

PMID- 9658181
TI  - Actin filaments and microtubules are involved in different membrane traffic
      pathways that transport sphingolipids to the apical surface of polarized HepG2
      cells.
AB  - In polarized HepG2 hepatoma cells, sphingolipids are transported to the apical,
      bile canalicular membrane by two different transport routes, as revealed with
      fluorescently tagged sphingolipid analogs. One route involves direct,
      transcytosis-independent transport of Golgi-derived glucosylceramide and
      sphingomyelin, whereas the other involves basolateral to apical transcytosis of
      both sphingolipids. We show that these distinct routes display a different
      sensitivity toward nocodazole and cytochalasin D, implying a specific transport
      dependence on either microtubules or actin filaments, respectively. Thus,
      nocodazole strongly inhibited the direct route, whereas sphingolipid transport by
      transcytosis was hardly affected. Moreover, nocodazole blocked
      "hyperpolarization," i.e., the enlargement of the apical membrane surface, which
      is induced by treating cells with dibutyryl-cAMP. By contrast, the transcytotic
      route but not the direct route was inhibited by cytochalasin D. The actin
      dependent step during transcytotic lipid transport probably occurs at an early
      endocytic event at the basolateral plasma membrane, because total lipid uptake
      and fluid phase endocytosis of horseradish peroxidase from this membrane were
      inhibited by cytochalasin D as well. In summary, the results show that the two
      sphingolipid transport pathways to the apical membrane must have a different
      requirement for cytoskeletal elements.

PMID- 9658183
TI  - J-104,871, a novel farnesyltransferase inhibitor, blocks Ras farnesylation in
      vivo in a farnesyl pyrophosphate-competitive manner.
AB  - Farnesylation of the activated ras oncogene product by protein
      farnesyltransferase (FTase) is a critical step for its oncogenic function.
      Because squalene synthase and FTase recruit farnesyl pyrophosphate as a common
      substrate, we modified squalene synthase (SS) inhibitors to develop FTase
      inhibitors. Among the compounds tested, a novel FTase inhibitor termed J-104,871
      inhibited rat brain FTase with an IC50 of 3.9 nM in the presence of 0.6 microM
      farnesyl pyrophosphate (FPP), whereas it scarcely inhibited rat brain protein
      geranylgeranyltransferase-I or SS. The in vitro inhibition of rat brain FTase by
      J-104,871 depends on the FPP concentration but not on the concentration of Ras
      peptide. Thus, in vitro studies strongly suggest that J-series compounds have an
      FPP-competitive nature. J-104,871 also inhibited Ras processing in activated H
      ras-transformed NIH3T3 cells with an IC50 value of 3.1 microM. We tested the
      effects of lovastatin and zaragozic acid A, which modify cellular FPP levels, on
      Ras processing of J-104,871. Lovastatin, a hepatic hydroxymenthyl coenzyme A
      reductase inhibitor that reduced the cellular FPP pool, increased the activity of
      J-104,871, whereas 3 microM zaragozic acid A, an SS inhibitor that raised the FPP
      level, completely abrogated the activity of J-104,871 even at 100 microM. These
      results suggest that J-104,871 inhibits FTase in an FPP-competitive manner in
      whole cells as well as in the in vitro system. Furthermore, J-104,871 suppressed
      tumor growth in nude mice transplanted with activated H-ras-transformed NIH3T3
      cells.

PMID- 9658184
TI  - Yeast expressed cytochrome P450 2D6 (CYP2D6) exposed on the external face of
      plasma membrane is functionally competent.
AB  - CYP2D6, a xenobiotic metabolizing cytochrome P450 (P450), was found to be present
      in significant amount on the outer face of cell plasma membrane in addition to
      the regular microsomal location. Present work demonstrates that this external
      P450 is catalytically competent and that activity is supported by NADPH-P450
      reductase present on the inner face of plasma membrane. Purified plasma membranes
      from yeast expressing CYP2D6 sustained NADPH- and cumene hydroperoxide-dependent
      dextromethorphan demethylation and NADPH-cytochrome c activity confirming
      previous observations in human hepatocytes. CYP2D6 found on the outside of plasma
      membrane (by differential immuno-inhibition and acidic shift assays on
      transformed spheroplasts) was catalytically competent at the cell surface for
      NADPH-supported activities. Anti-yeast P450-reductase antibodies inhibited
      neither CYP2D6 nor P450-reductase activities upon incubation with intact
      spheroplasts. In contrast, both activities were inhibited on isolated plasma
      membrane fragments. This highly suggested a cytosolic-orientation of the plasma
      membrane P450-reductase. This finding was confirmed by immunostaining in confocal
      microscopy. Finally, gene deletion of P450-reductase caused a complete loss of
      plasma membrane NADPH-supported CYP2D6 activity, which suggests that the
      reductase participates to some degree in the transmembrane electron transfer
      chain. This work illustrates that the outside-exposed plasma membrane CYP2D6 is
      active and may play an important metabolic role.

PMID- 9658185
TI  - Protein kinase C-mediated down-regulation of beta1-adrenergic receptor gene
      expression in rat C6 glioma cells.
AB  - In the current study, we investigated the mechanism by which protein kinase C
      (PKC) regulates the expression of beta1-adrenergic receptor (beta1AR) mRNA in rat
      C6 glioma cells. Exposure of the cells to 4beta-phorbol-12-myristate-13-acetate
      (PMA), an activator PKC, resulted in a down-regulation of both beta1AR binding
      sites and mRNA levels in a time- and concentration-dependent manner. This effect
      was not observed with phorbol esters that do not activate PKC and was blocked by
      bisindolylmaleimide, a specific PKC inhibitor. Activation of PKC did not reduce
      the half-life of beta1AR mRNA but significantly decreased the activity of the
      beta1AR promoter, as determined by reporter analysis. A putative response
      element, with partial homology to a consensus cAMP response element, was
      identified by mutation analysis of the promoter at positions -343 to -336,
      relative to the translational start site. Mutation of this putative regulatory
      element, referred to as a beta1AR-PKC response element, completely blocked the
      PKC-mediated down-regulation of beta1AR promoter activity. Gel mobility shift
      analysis detected two specific bands when C6 cell extracts were incubated with a
      labeled DNA probe containing the beta1AR-PKC response element sequence. Formation
      of one of these bands was inhibited by an oligonucleotide probe containing a
      consensus CRE and disrupted by an antibody for cAMP response element binding
      protein. Based on these studies, we propose that the PKC-induced down-regulation
      of beta1AR gene transcription in C6 cells is mediated in part by a cAMP response
      element binding protein-dependent mechanism acting on a novel response element.

PMID- 9658186
TI  - Isoquinolines as antagonists of the P2X7 nucleotide receptor: high selectivity
      for the human versus rat receptor homologues.
AB  - 1-[N, O-Bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (KN
      62) and N-[1-[N-methyl-p-(5 isoquinolinesulfonyl)benzyl]-2-(4
      phenylpiperazine)ethyl]-5-isoquinolinesulfonamide (KN-04) potently inhibit the
      human lymphocyte P2Z receptor, an ATP-gated cation channel [Br J Pharmacol
      120:1483-1490 (1997)]. Although the molecular identity of the lymphocyte P2Z
      receptor has not been established, it shares many functional characteristics with
      the cloned P2X7 nucleotide receptor. We have tested whether these isoquinolines
      inhibit P2X receptor function in human embryonic kidney 293 cells that stably
      express the human or rat recombinant P2X7 receptors. ATP activation of cation
      currents and uptake of the organic dye ethidium were potently inhibited by KN-62
      and KN-04 in human embryonic kidney cells expressing the human P2X7R but not the
      rat P2X7R, even though these species homologues share 80% amino acid identity.
      Introduction of the first 335 amino acids of the human P2X7R sequence conferred
      KN-62 sensitivity to the rat P2X7R; this suggests that isoquinolines interact
      with residues in the amino-terminal half (containing the large extracellular
      loop) of the human P2X7R. KN-62 and KN-04 also potently inhibited ATP-gated Ca2+
      influx and ethidium uptake in several leukocyte cell lines (THP-1, BAC1.2f5, and
      BW5147) that natively express the human or murine P2X7R mRNA. The ability of
      isoquinoline sulfonamides to potently inhibit human and murine P2X7R signaling
      will be a useful tool for identifying P2Z/P2X7 functional responses in other cell
      types. The substantial differences in pharmacological sensitivity between rat and
      human P2X7R may also indicate structural domains important in channel/pore
      activation.

PMID- 9658187
TI  - Photoaffinity labeling of the benzodiazepine binding site of alpha1beta3gamma2
      gamma-aminobutyric acidA receptors with flunitrazepam identifies a subset of
      ligands that interact directly with His102 of the alpha subunit and predicts
      orientation of these within the benzodiazepine pharmacophore.
AB  - Photoincorporation of ligands into the benzodiazepine site of native gamma
      aminobutyric acidA (GABAA) receptors provides useful information about the nature
      of the benzodiazepine (BZ) binding site. Photoincorporation of flunitrazepam into
      a single population of GABAA receptors, recombinant human alpha1beta3gamma2, was
      investigated to probe further the mechanism and orientation of flunitrazepam and
      other ligands in the BZ binding site. It was concluded that the receptor is
      primarily derivatized with the entire, unfragmented, flunitrazepam molecule,
      which undergoes a conformational change during photolysis and largely vacates the
      benzodiazepine binding site. Investigation of the BZ site after
      photoincorporation of [3H]flunitrazepam confirmed that binding of other
      radioligands was unaffected by incorporation of flunitrazepam. This did not
      correlate with their efficacy but depended on the presence of particular
      structural features in the molecule. It was observed that affected compounds have
      a pendant phenyl moiety, analogous to the 5-phenyl group of flunitrazepam, which
      are proposed to overlap and interact with the same residue or residues in the BZ
      binding site. Because the major site of flunitrazepam photoincorporation has been
      shown to be His102, we propose that this group of compounds interacts directly
      with His 102, whereas compounds of other structural types have no direct
      interaction with this amino acid. The orientation of ligands within the BZ
      binding site and their specific interaction with identified amino acids are not
      well understood. The data in the current study indicate that His102 interacts
      directly with the pendant phenyl group of diazepam, and further implications for
      the pharmacophore of the BZ binding site are discussed.

PMID- 9658188
TI  - Phosphorylation and functional desensitization of the alpha2A-adrenergic receptor
      by protein kinase C.
AB  - We have investigated the potential for protein kinase C (PKC) to phosphorylate
      and desensitize the alpha2A-adrenergic receptor (alpha2AAR). In whole-cell
      phosphorylation studies, recombinantly expressed human alpha2AAR displayed an
      increase in phosphorylation after short-term exposure to 100 nM phorbol 12
      myristate-13-acetate (PMA) that was blocked by preincubation with a PKC
      inhibitor. This increase in receptor phosphorylation over basal amounted to 172
      +/- 40% in COS-7 cells and 201 +/- 40% in Chinese hamster ovary cells. In
      permanently transfected Chinese hamster fibroblast cells, PKC activation by brief
      exposure of the cells to PMA resulted in a marked desensitization of alpha2AAR
      function, amounting to a 68 +/- 4% decrease in the maximal agonist (UK14304)
      stimulated intracellular calcium release. Such desensitization was blocked by the
      PKC inhibitor bisindolylmaleimide I and was not evoked by an inactive phorbol
      ester. The desensitization of this agonist response was not caused by PKC
      mediated augmentation of G protein-coupled receptor kinase activity, because PMA
      promoted desensitization of a mutated alpha2AAR that lacked G protein-coupled
      receptor kinase phosphorylation sites was identical to that of wild-type
      alpha2AAR. To test whether PKC phosphorylation is a mechanism by which alpha2AAR
      can be regulated by other receptors, the alpha1bAR was co-expressed with the
      alpha2AAR in Chinese hamster ovary cells. Upon selective activation of alpha1bAR,
      the function of alpha2AAR underwent a 53 +/- 5% desensitization. Thus, cellular
      events that result in PKC activation promote phosphorylation of the alpha2AAR and
      lead to substantial desensitization of receptor function. This heterologous
      regulation also represents a mechanism by which rapid crosstalk between the
      alpha2AAR and other receptors can occur.

PMID- 9658189
TI  - Protein-linked DNA strand breaks induced by NSC 314622, a novel noncamptothecin
      topoisomerase I poison.
AB  - NSC 314622 was found to have a cytotoxicity profile comparable to the
      topoisomerase I (top1) inhibitors camptothecin (CPT) and saintopin in the
      National Cancer Institute In Vitro Anticancer Drug Discovery Screen using the
      COMPARE analysis. In vitro data showed that NSC 314622 induced DNA cleavage in
      the presence of top1 at micromolar concentrations. Cleavage specificity was
      different from CPT in that NSC 314622 did not cleave all sites induced by CPT
      whereas some sites were unique to the NSC 314622 treatment. Top1-induced DNA
      cleavage was also more stable than cleavage induced by CPT. NSC 314622 did not
      induce DNA cleavage in the presence of human topoisomerase II. High
      concentrations of NSC 314622 did not produce detectable DNA unwinding, which
      suggests that NSC 314622 is not a DNA intercalator. DNA damage analyzed in human
      breast carcinoma MCF7 cells by alkaline elution showed that NSC 314622 induced
      protein-linked DNA single-strand breaks that reversed more slowly than CPT
      induced strand breaks. CEM/C2, a CPT-resistant cell line because of a top1 point
      mutation [Cancer Res 55:1339-1346 (1995)], was cross-resistant to NSC 314622.
      These results demonstrate that NSC 314622 is a novel top1-targeted drug with a
      unique chemical structure.

PMID- 9658190
TI  - A crucial role for the mitogen-activated protein kinase pathway in nicotinic
      cholinergic signaling to secretory protein transcription in pheochromocytoma
      cells.
AB  - The mitogen-activated protein kinase (MAPK) pathway plays a pivotal role in
      intracellular signaling, and this cascade may impinge on cAMP response elements
      (CREs) of target genes. Both the MAPK pathway and chromogranin A expression may
      be activated by cytosolic calcium influx, and calcium-dependent signals map onto
      the chromogranin A promoter proximal CRE. We therefore probed the role of the
      MAPK pathway in chromogranin A biosynthesis after secretory stimulation of PC12
      pheochromocytoma cells by the nicotinic cholinergic pathway, the physiological
      secretory trigger. Chemical inhibition of either MAPK or MAPK kinase blocked the
      response of a transfected chromogranin A promoter to nicotine or protein kinase C
      activation [by phorbol-12-myristate-13-acetate (PMA)], although nicotine-evoked
      catecholamine secretion was unaffected. Activation of the MAP kinase cascade
      (Ras, Raf, MAPK, or CREB kinase) by cotransfection of pathway components
      stimulated the chromogranin A promoter. Cotransfection of MAPK pathway dominant
      negative mutants (for Raf, MAPK, or CREB kinase) blocked nicotinic or PMA
      activation of chromogranin A, although a dominant negative Ras mutant was without
      effect. MAPK pathway enzymatic activity was stimulated by both nicotine and PMA.
      Point mutations of the chromogranin A CRE suggested that this element was
      necessary in cis for stimulation by nicotine, PMA, or chemical activation of the
      MAPK pathway. Transfer of the CRE to a heterologous promoter conferred
      inducibility by not only nicotine or cAMP but also MAPK activation. Expression of
      the CREB antagonist KCREB blocked the response of the chromogranin A promoter to
      nicotine, cAMP, or MAPK pathway activation by either chemical stimulation or
      cotransfection of active cascade components. Chromogranin A mRNA responded to
      MAPK pathway manipulation in a fashion similar to the transfected chromogranin A
      promoter, in both direction and magnitude. We conclude that the MAPK pathway is a
      necessary intermediate in signaling from the nicotinic receptor to secretory
      protein transcription, although not to catecholamine secretion. In trans, this
      response seems to involve the following signal cascade: protein kinase C --> Raf 
      -> MAPK kinase --> MAPK --> CREB kinase --> CREB. In cis, activation by the
      cascade maps onto the chromogranin A promoter proximal CRE, which is both
      necessary and sufficient to confer the response.

PMID- 9658191
TI  - Sphingosine kinase mediates cyclic AMP suppression of apoptosis in rat periosteal
      cells.
AB  - Prostaglandin E stimulates bone formation in humans and animals, and increases
      intracellular cAMP in osteoblastic cells. We found that cAMP inhibits apoptosis
      in osteoblastic cells, and examined the mechanism of this effect. We report that
      the cAMP elevating agent, forskolin, increases cell number in the rat periosteal
      cell line (RP-11), by suppressing apoptosis in a cell type-specific manner. In RP
      11, forskolin transiently up-regulates extracellular signal-regulated kinase
      activity, a known suppressor of apoptosis. PD98059, a selective inhibitor of the
      extracellular signal-regulated kinase pathway, only partially reverses the
      antiapoptotic effect of forskolin, which suggests an additional mechanism for
      cAMP action. We found that forskolin stimulates cytosolic sphingosine kinase
      (SPK) activity in these cells; in two other osteoblastic cell lines, however,
      forskolin does not suppress apoptosis. In contrast to the partial opposing effect
      of PD98059 to forskolin action, N, N-dimethylsphingosine, a specific inhibitor of
      SPK, completely reverses the antiapoptotic effect of forskolin, and has no effect
      on apoptosis in the absence of forskolin. These findings show for the first time
      that cAMP activates SPK in a cell-type-specific manner, and suggest that cAMP
      suppression of apoptosis in RP-11 periosteal cells is mediated by its stimulation
      of SPK.

PMID- 9658192
TI  - Etoposide targets topoisomerase IIalpha and IIbeta in leukemic cells: isoform
      specific cleavable complexes visualized and quantified in situ by a novel
      immunofluorescence technique.
AB  - We have shown that both DNA topoisomerase (topo) IIalpha and beta are in vivo
      targets for etoposide using a new assay which directly measures topo IIalpha and
      beta cleavable complexes in individual cells after treatment with topo II
      targeting drugs. CCRF-CEM human leukemic cells were exposed to etoposide for 2
      hr, then embedded in agarose on microscope slides before cell lysis. DNA from
      each cell remained trapped in the agarose and covalently bound topo II molecules
      from drug-stabilized cleavable complexes remained associated with the DNA. The
      covalently bound topo II was detected in situ by immunofluorescence. Isoform
      specific covalent complexes were detected with antisera specific for either the
      alpha or beta isoform of topo II followed by a fluorescein isothiocyanate
      conjugated second antibody. DNA was detected using the fluorescent stain Hoechst
      33258. A cooled slow scan charged coupled device camera was used to capture
      images. A dose-dependent increase in green immunofluorescence was observed when
      using antisera to either the alpha or beta isoforms of topo II, indicating that
      both isoforms are targets for etoposide. We have called this the TARDIS method,
      for trapped in agarose DNA immunostaining. Two key advantages of the TARDIS
      method are that it is isoform-specific and that it requires small numbers of
      cells, making it suitable for analysis of samples from patients being treated
      with topo II-targeting drugs. The isoform specificity will enable us to extend
      our understanding of the mechanism of interaction between topo II-targeting
      agents and their target, the two human isoforms.

PMID- 9658193
TI  - Point mutation in intron sequence causes altered carboxyl-terminal structure in
      the aryl hydrocarbon receptor of the most 2,3,7,8-tetrachlorodibenzo-p-dioxin
      resistant rat strain.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent dioxin. There are
      exceptionally wide inter- and intraspecies differences in sensitivity to TCDD
      toxicity with Han/Wistar (H/W) (Kuopio) rats being the most resistant mammals
      tested. A peculiar feature of H/W rats is that despite their unresponsiveness to
      the acute lethality of TCDD, their sensitivity to other biological impacts of
      TCDD (e.g., CYP1A1 induction) is preserved. The biological effects of TCDD are
      mediated by the aryl hydrocarbon receptor (AhR). We recently found that the AhR
      of H/W rats (about 98 kDa) is smaller than the receptor in other rat strains (106
      kDa). In the present study, molecular cloning and sequencing of the H/W rat AhR
      revealed that the reason for its smaller size is a deletion/insertion-type change
      at the 3' end of exon 10 in the receptor cDNA. This change emanates from a single
      point mutation at the first nucleotide of intron 10, resulting in altered mRNA
      splicing. At the protein level, the mutation leads to a total loss of either 43
      or 38 amino acids (with altered sequence for the last seven amino acids in the
      latter case) toward the carboxyl-terminal end in the trans-activation domain of
      the AhR. H/W rats also harbor a point mutation in exon 10 that will cause a Val
      to-Ala substitution in codon 497, but this occurs in a variable region of the
      AhR. These findings suggest that there is a relatively small region in the AhR
      trans-activation domain that may be capable of providing selectivity to its
      function.

PMID- 9658194
TI  - Effector pathway-dependent relative efficacy at serotonin type 2A and 2C
      receptors: evidence for agonist-directed trafficking of receptor stimulus.
AB  - There are many examples of a single receptor coupling directly to more than one
      cellular signal transduction pathway. Although traditional receptor theory allows
      for activation of multiple cellular effectors by agonists, it predicts that the
      relative degree of activation of each effector pathway by an agonist (relative
      efficacy) must be the same. In the current experiments, we demonstrate that
      agonists at the human serotonin2A (5-HT2A) and 5-HT2C receptors activate
      differentially two signal transduction pathways independently coupled to the
      receptors [phospholipase C (PLC)-mediated inositol phosphate (IP) accumulation
      and phospholipase A2 (PLA2)-mediated arachidonic acid (AA) release]. The relative
      efficacies of agonists differed depending on which signal transduction pathway
      was measured. Moreover, relative to 5-HT, some 5-HT2C agonists (e.g., 3
      trifluoromethylphenyl-piperazine) preferentially activated the PLC-IP pathway,
      whereas others (e.g., lysergic acid diethylamide) favored the PLA2-AA pathway. In
      contrast, when two dependent responses were measured (IP accumulation and calcium
      mobilization), agonist relative efficacies were not different. These data
      strongly support the hypothesis termed "agonist-directed trafficking of receptor
      stimulus" recently proposed by Kenakin [Trends Pharmacol Sci 16:232-238 (1995)].
      Concentration-response curves to 5-HT2C agonists were fit well by a three-state
      model of receptor activation, suggesting that two active receptor states may be
      sufficient to explain pathway-dependent agonist efficacy. Rational drug design
      that optimizes preferential effector activity within a group of receptor
      selective drugs holds the promise of increased selectivity in clinically useful
      agents.

PMID- 9658195
TI  - Differential response of estrogen receptor alpha and estrogen receptor beta to
      partial estrogen agonists/antagonists.
AB  - The existence of two rather than one estrogen receptor, today characterized as
      estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta), indicates
      that the mechanism of action of 17beta-estradiol and related synthetic drugs is
      more complex than previously thought. Because the homology of amino acid residues
      in the ligand-binding domain (LBD) of ERbeta is high compared with those amino
      acid residues in ERalpha LBD, previously shown to line the ligand binding cavity
      or to make direct contacts with ligands, it is not surprising that many ligands
      have a similar affinity for both receptor subtypes. We report that 17alpha
      ethynyl, 17beta-estradiol, for example, has an ERalpha-selective agonist potency
      and that 16beta,17alpha-epiestriol has an ERbeta-selective agonist potency. We
      also report that genistein has an ERbeta-selective affinity and potency but an
      ERalpha-selective efficacy. Furthermore, we show that tamoxifen, 4-OH-tamoxifen,
      raloxifene, and ICI 164,384 have an ERalpha-selective partial agonist/antagonist
      function but a pure antagonist effect through ERbeta. In addition, raloxifene
      displayed an ERalpha-selective antagonist potency, in agreement with its ERalpha
      selective affinity. However, although ICI 164,384 showed an ERbeta-selective
      affinity, it had a similar potency to antagonize the effect of 17beta-estradiol
      in the ERalpha- and ERbeta-specific reporter cell lines, respectively. In
      conclusion, our data indicate that the ligand binding cavity of ERbeta is
      probably more different from that of ERalpha than can be anticipated from the
      primary sequences of the two ER subtypes and that it will be possible to develop
      receptor-specific ligands that may form the basis of novel pharmaceuticals with
      better in vivo efficacy and side effect profile than current available drugs.

PMID- 9658196
TI  - Molecular basis for the lack of HERG K+ channel block-related cardiotoxicity by
      the H1 receptor blocker cetirizine compared with other second-generation
      antihistamines.
AB  - In the current study, the potential blocking ability of K+ channels encoded by
      the human ether-a-go-go related gene (HERG) by the piperazine H1 receptor
      antagonist cetirizine has been examined and compared with that of other second
      generation antihistamines (astemizole, terfenadine, and loratadine). Cetirizine
      was completely devoid of any inhibitory action on HERG K+ channels heterologously
      expressed in Xenopus laevis oocytes in concentrations up to 30 microM. On the
      other hand, terfenadine and astemizole effectively blocked HERG K+ channels with
      nanomolar affinities (the estimated IC50 values were 330 and 480 nM,
      respectively), whereas loratadine was approximately 300-fold less potent (IC50
      approximately 100 microM). In addition, in contrast to terfenadine, cetirizine
      did not show use-dependent blockade. In SH-SY5Y cells, a human neuroblastoma
      clone that constitutively expresses K+ currents carried by HERG channels (IHERG),
      as well as in human embryonic kidney 293 cells stably transfected with HERG cDNA,
      extracellular perfusion with 3 microM cetirizine did not exert any inhibitory
      action on IHERG. Astemizole (3 microM), on the other hand, was highly effective.
      Terfenadine (3 microM) caused a marked (approximately 80%) inhibition of IHERG in
      SH-SY5Y cells, whereas loratadine, at the same concentration, caused a 40%
      blockade. Furthermore, the application of cetirizine (3 microM) on the
      intracellular side of the membrane of HERG-transfected human embryonic kidney 293
      cells did not affect IHERG, whereas the same intracellular concentration of
      astemizole caused a complete block. The results of the current study suggest that
      second-generation antihistamines display marked differences in their ability to
      block HERG K+ channels. Cetirizine in particular, which possesses more polar and
      smaller substituent groups attached to the tertiary amine compared with other
      antihistamines, lacks HERG-blocking properties, possibly explaining the absence
      of torsade de pointes ventricular arrhythmias associated with its therapeutical
      use.

PMID- 9658197
TI  - Regulation of adenylyl cyclase type V/VI in smooth muscle: interplay of
      inhibitory G protein and Ca2+ influx.
AB  - The characteristics of inhibitory regulation of adenylyl cyclase V/VI by Ca2+ and
      G proteins were examined in dispersed gastric smooth muscle cells. The mechanisms
      were evoked separately, sequentially, or concurrently using ligand-gated and G
      protein-coupled receptor agonists and receptor-independent probes (e. g,
      thapsigargin). During the initial phase of agonist stimulation, alpha,beta
      methylene-ATP, UTP, and ATP inhibited forskolin-stimulated cAMP formation in a
      concentration-dependent fashion. Inhibition by alpha,beta-methylene-ATP, which
      activates ligand-gated P2X receptors, was abolished by zero Ca2+, whereas
      inhibition by UTP, which activates P2Y2 receptors coupled to Gq/11 and Gi3, was
      not affected by zero Ca2+ but was abolished by pertussis toxin (PTX). Inhibition
      by ATP, which activates both P2X and P2Y2 receptors, was not affected by zero
      Ca2+ alone; but after inhibition mediated by Galphai3 was blocked with PTX,
      inhibition by Ca2+ influx was unmasked and was abolished by zero Ca2+. Inhibition
      by cholecystokinin-8 was observed only during the phase of capacitative Ca2+
      influx and was blocked by zero Ca2+. Inhibition by UTP during this phase was not
      affected by zero Ca2+ alone; but after inhibition mediated by Galphai3 was
      blocked with PTX, inhibition by Ca2+ influx was unmasked and was abolished by
      zero Ca2+. Inhibition of adenylyl cyclase V/VI activity in smooth muscle can be
      mediated independently by inhibitory G proteins and Ca2+ influx but is
      exclusively mediated by inhibitory G proteins when both mechanisms are triggered.

PMID- 9658198
TI  - Ligand specificity of the genetic variants of human alpha1-acid glycoprotein:
      generation of a three-dimensional quantitative structure-activity relationship
      model for drug binding to the A variant.
AB  - Human alpha1-acid glycoprotein (AAG) is a mixture of at least two genetic
      variants: the A variant and the F1 and/or S variant or variants, which are
      encoded by two different genes. In a continuation of previous studies indicating
      specific drug transport roles for each AAG variant according to its separate
      genetic origin, this work was designed to (1) determine the affinities of the two
      main gene products of AAG (i.e., the A variant and a mixture of the F1 and S
      variants) for 35 chemically diverse drugs and (2) to obtain meaningful 3D-QSARs
      for each binding site. Affinities were obtained by displacement experiments,
      leading to qualitative indications about binding site characteristics. In
      particular, drugs binding selectively to the A variant displayed some common
      structural features, but this was not seen for the F1*S variants. Three
      dimensional QSAR analyses using the CoMFA method yielded a steric model for
      binding to the A variant, from which a simplified haptophoric model was derived.
      In contrast, no statistically sound model was found for the F1*S variants,
      possibly due (among other reasons) to an insufficient number of high affinity
      ligands in the set.

PMID- 9658199
TI  - Identification of a [3H]Ligand for the common allosteric site of muscarinic
      acetylcholine M2 receptors.
AB  - Muscarinic acetylcholine receptors bind allosteric modulators at a site apart
      from the orthosteric site used by conventional ligands. We tested in cardiac
      tissue whether modulator binding to ligand-occupied muscarinic M2 receptors is a
      preferential event that can be detected using a radioactive allosteric agent. The
      newly synthesized dimethyl-W84 (N,N'-bis[3-(1,3-dihydro-1, 3-dioxo-4-methyl-2H
      isoindol-2-yl)propyl]-N,N,N',N'-tetramethyl-1, 6-hexanediaminium diiodide) has a
      particular high potency at M2 receptors occupied by the conventional antagonist N
      methylscopolamine (NMS); dissociation of [3H]NMS is half-maximally retarded at an
      EC50,diss value of 3 nM. Using obidoxime as an "allosteric antagonist," evidence
      was found that dimethyl-W84 interacts with the postulated common allosteric site.
      Binding of [3H]dimethyl-W84 (0.3 nM; specific activity, 168 Ci/mmol) was measured
      in porcine heart homogenates (4 mM Na2HPO4, 1 mM KH2PO4, pH 7.4, 23 degrees) in
      the presence of 1 microM NMS. Homologous competition experiments revealed two
      components of saturable radioligand binding: one with a high affinity (KD = 2 nM)
      and small capacity ( approximately 30% of total saturable binding) and the other
      with a 20,000-fold lower affinity. The Bmax value of the high affinity sites (68
      fmol/mg protein) matched muscarinic receptor density as determined by [3H]NMS (79
      fmol/mg). Prototype allosteric agents, alcuronium, W84 (the parent compound of
      the radioligand), and gallamine, displaced high affinity [3H]dimethyl-W84 binding
      concentration-dependently (pKi values = 8.62, 7.83, and 6.72, respectively). The
      binding affinities of the modulators were in excellent correlation with their
      potencies to allosterically stabilize NMS/receptor complexes (EC50,diss = 8.40,
      7.72, and 6.74, respectively). We conclude that high affinity binding of
      [3H]dimethyl-W84 reflects occupation of the common allosteric site of M2
      receptors.

PMID- 9658200
TI  - Mutations at lipid-exposed residues of the acetylcholine receptor affect its
      gating kinetics.
AB  - The firmest candidate among the transmembrane portions of the nicotinic
      acetylcholine receptor (AChR) to be in contact with the lipid bilayer is the
      fourth segment, M4. To explore the contribution of alphaM4 amino acid residues of
      mouse AChR to channel gating, we combined site-directed mutagenesis with single
      channel recordings. Two residues in alphaM4, Cys418 and Thr422, were found to
      significantly affect gating kinetics when replaced by alanine. AChRs containing
      alphaC418A and alphaT422A subunits form channels characterized by a 3- and 5-fold
      reduction in the mean open time, respectively, suggesting an increase in the
      closing rate due to the mutations. The calculated changes in the energy barrier
      for the channel closing process show unequal and coupled contributions of both
      positions to channel gating. Single-channel recordings of hybrid wild-type
      alpha/alphaT422A AChR show that the closing rate depends on the number of alpha
      subunits mutated. Each substitution of threonine to alanine changes the energy
      barrier of the closing process by approximately 0.5 kcal/mol. Recordings of
      channels activated by high agonist concentration suggest that these mutations
      also impair channel opening. Both Cys418 and Thr422 have been postulated to be in
      contact with the lipid milieu and are highly conserved among species and
      subunits. Our results support the involvement of lipid-exposed residues in
      alphaM4 in AChR channel gating mechanism.

PMID- 9658201
TI  - Chimeric melanocortin MC1 and MC3 receptors: identification of domains
      participating in binding of melanocyte-stimulating hormone peptides.
AB  - The melanocortin receptors MC1 and MC3 are G protein-coupled receptors that have
      substantial structural similarities and bind melanocyte peptides but with
      different affinity profiles. We constructed a series of chimeric MC1/MC3
      receptors to identify the epitopes that determine their selectivities for natural
      melanocyte peptides and synthetic analogues. The chimeric constructs were made by
      a polymerase chain reaction that used identical regions in or just outside
      transmembranes (TM) 1, 4, and 6 and divided the receptors into four segments.
      Saturation and competition studies on the expressed chimeric proteins indicate
      that TM1, TM2, TM3, and TM7 are involved in the subtype-specific binding of
      melanocyte peptides to these receptors. The results support the hypothesis that
      TM4 and TM5 may not contribute to the ligand-binding specificity of the MC
      receptors. This is the first report to describe the subtype-specific hormone
      binding domains of the melanocortin receptor family.

PMID- 9658202
TI  - Structural determinants of potency and stereoselective block of hKv1.5 channels
      induced by local anesthetics.
AB  - Block of hKv1.5 channels by bupivacaine is stereoselective, with (R)-(+)
      bupivacaine being 7-fold more potent than (S)-(-)-bupivacaine. The study of the
      effects of chemically related enantiomers on these channels may help to elucidate
      the structural determinants of stereoselective hKv1.5 channels block by local
      anesthetics. In this study, we analyzed the effects of (R)-(+)-ropivacaine, (R)
      (+)-mepivacaine, and (S)-(-)-mepivacaine on hKv1.5 channels stably expressed in
      Ltk- cells. (R)-(+)-Ropivacaine inhibited hKv1.5 current and induced a fast
      initial decline superimposed to the slow inactivation during the application of
      depolarizing pulses, which reached steady state at the end of 250-msec
      depolarizing pulses. The concentration-dependence block induced by (R)-(+)
      ropivacaine yielded a KD value of 32 +/- 1 microM [i.e., 2.5-fold more potent
      than (S)-(-)-ropivacaine]. (R)-(+)-Ropivacaine block also was voltage dependent,
      with a fractional electrical distance (delta) of 0.156 +/- 0.003 (n = 14)
      referred to the inner surface. Both (S)-(-)- and (R)-(+)-mepivacaine blocked
      hKv1.5 channels, with KD values of 286.8 +/- 34.1 and 379.0 +/- 56.0 microM,
      respectively [i.e., block was not stereoselective (p > 0.05)]. (S)-(-)
      Mepivacaine and (R)-(+)-mepivacaine block displayed no apparent time-dependence
      due to a very fast dissociation rate constant. However, block by mepivacaine
      enantiomers was voltage dependent, with delta values of 0.154 +/- 0.015 and 0.160
      +/- 0.008 for the (S)-(-)- and (R)-(+)-enantiomers, respectively. We conclude
      that (1) (R)-(+)-ropivacaine and mepivacaine enantiomers block the open state of
      hKv1.5 channels and (2) the length of their alkyl substituent at position 1
      determines the potency and the degree of stereoselectivity.

PMID- 9658203
TI  - Access to hematin: the basis of chloroquine resistance.
AB  - The saturable uptake of chloroquine by parasites of Plasmodium falciparum has
      been attributed to specific carrier-mediated transport of chloroquine. It is
      suggested that chloroquine is transported in exchange for protons by the parasite
      membrane Na+/H+ exchanger [J Biol Chem 272:2652-2658 (1997)]. Once inside the
      parasite, it is proposed that chloroquine inhibits the polymerization of hematin,
      allowing this toxic hemoglobin metabolite to accumulate and kill the cell
      [Pharmacol Ther 57:203-235 (1993)]. To date, the contribution of these proposed
      mechanisms to the uptake and antimalarial activity of chloroquine has not been
      assessed. Using sodium-free medium, we demonstrate that chloroquine is not
      directly exchanged for protons by the plasmodial Na+/H+ exchanger. Furthermore,
      we show that saturable chloroquine uptake at equilibrium is due solely to the
      binding of chloroquine to hematin rather than active uptake: using Ro 40-4388, a
      potent and specific inhibitor of hemoglobin digestion and, by implication,
      hematin release, we demonstrate a concentration-dependent reduction in the number
      of chloroquine binding sites. An equal number of chloroquine binding sites are
      found in both resistant and susceptible clones, but the apparent affinity of
      chloroquine binding is found to correlate with drug activity (r2 = 0.93, p <
      0.0001). This completely accounts for both the reduced drug accumulation and
      activity observed in resistant clones and the "reversal" of resistance produced
      by verapamil. The data presented here reconcile most of the available biochemical
      data from studies of the mode of action of chloroquine and the mechanism of
      chloroquine resistance. We show that the activity of chloroquine and amodiaquine
      is directly dependent on the saturable binding of the drugs to hematin and that
      the inhibition of hematin polymerization may be secondary to this binding. The
      chloroquine-resistance mechanism regulates the access of chloroquine to hematin.
      Our model is consistent with a resistance mechanism that acts specifically at the
      food vacuole to alter the binding of chloroquine to hematin rather than changing
      the active transport of chloroquine across the parasite plasma membrane.

PMID- 9658204
TI  - Human platelets and polymorphonuclear leukocytes synthesize oxygenated
      derivatives of arachidonylethanolamide (anandamide): their affinities for
      cannabinoid receptors and pathways of inactivation.
AB  - Arachidonylethanolamide (AEA), the putative endogenous ligand of the cannabinoid
      receptor, has been shown to be a substrate for lipoxygenase enzymes in vitro. One
      goal of this study was to determine whether lipoxygenase-rich cells metabolize
      AEA. [14C]AEA was converted by human polymorphonuclear leukocytes (PMNs) to two
      major metabolites that comigrated with synthetic 12(S)- and 15(S)-hydroxy
      arachidonylethanolamide (HAEA). Human platelets convert [14C]AEA to 12(S)-HAEA.
      12(S)-HAEA binds to both CB1 and CB2 receptors with approximately the same
      affinity as AEA. 12(R)-HAEA, which is not produced by PMNs, has 2-fold lower
      affinity for the CB1 receptor and 10-fold lower affinity for the CB2 receptor
      than 12(S)-HAEA. 15-HAEA has a lower affinity than AEA for both receptors, with
      Ki values of 738 and >1000 nM for CB1 and CB2 receptors, respectively. The
      addition of a hydroxyl group at C20 of AEA resulted in a ligand with the same
      affinity for the CB1 receptor but a 4-fold lower affinity for the CB2 receptor
      than AEA. 12(S)-HAEA and 15-HAEA are poor substrates for AEA amidohydrolase and
      do not bind to the AEA uptake carrier. In conclusion, the addition of a hydroxyl
      group at C12 of the arachidonate backbone of AEA does not affect binding to CB
      receptors but is likely to increase its half-life. The addition of hydroxyl
      groups at other positions affects ligand affinity for CB receptors; both the
      position of the hydroxyl group and the configuration of the remaining double
      bonds are determinants of affinity.

PMID- 9658205
TI  - Molecular basis for differential inhibition of glutamate transporter subtypes by
      zinc ions.
AB  - Zinc ions (Zn2+) are stored in synaptic vesicles with glutamate in a number of
      regions of the brain. When released into the synapse, Zn2+ modulates the activity
      of various receptors and ion channels. Excitatory amino acid transporters (EAATs)
      maintain extracellular glutamate concentrations below toxic levels and regulate
      the kinetics of glutamate receptor activation. We have investigated the actions
      of Zn2+ on two of the most abundant human excitatory amino acid transporters,
      EAAT1 and EAAT2. Zn2+ is a noncompetitive, partial inhibitor of glutamate
      transport by EAAT1 with an IC50 value of 9.9 +/- 2.3 microM and has no effect on
      glutamate transport by EAAT2 at concentrations up to 300 microM. Glutamate and
      aspartate transport by EAAT1 are associated with an uncoupled chloride
      conductance, but Zn2+ selectively inhibits transport and increases the relative
      chloride flux through the transporter. We have investigated the molecular basis
      for differential inhibition of EAAT1 and EAAT2 by Zn2+ using site-directed
      mutagenesis and demonstrate that histidine residues of EAAT1 at positions 146 and
      156 form part of the Zn2+ binding site. EAAT2 contains a histidine residue at the
      position corresponding to histidine 146 of EAAT1, but at the position
      corresponding to histidine 156 of EAAT1, EAAT2 has a glycine residue. Mutation of
      this glycine residue in EAAT2 to histidine generates a Zn2+ sensitive
      transporter, further confirming the role of this residue in conferring
      differential Zn2+ sensitivity.

PMID- 9658206
TI  - The biophysical and pharmacological characteristics of skeletal muscle ATP
      sensitive K+ channels are modified in K+-depleted rat, an animal model of
      hypokalemic periodic paralysis.
AB  - We evaluated the involvement of the sarcolemmal ATP-sensitive K+ channel in the
      depolarization of skeletal muscle fibers occurring in an animal model of human
      hypokalemic periodic paralysis, the K+-depleted rat. After 23-36 days of
      treatment with a K+-free diet, an hypokalemia was observed in the rats. No
      difference in the fasting insulinemia and glycemia was found between normokalemic
      and hypokalemic rats. The fibers of the hypokalemic rats were depolarized. In
      these fibers, the current of sarcolemmal ATP-sensitive K+ channels measured by
      the patch-clamp technique was abnormally reduced. Cromakalim, a K+ channel
      opener, enhanced the current and repolarized the fibers. At channel level, two
      open conductance states blocked by ATP and stimulated by cromakalim were found in
      the hypokalemic rats. The two states could be distinguished on the basis of their
      slope conductance and open probability and were never detected on muscle fibers
      of normokalemic rats. It is known that insulin in humans affected by hypokalemic
      periodic paralysis leads to fiber depolarization and provokes paralysis. We
      therefore examined the effects of insulin at macroscopic and single-channel level
      on hypokalemic rats. In normokalemic animals, insulin applied in vitro to the
      muscles induced a glybenclamide-sensitive hyperpolarization of the fibers and
      also stimulated the sarcolemmal ATP-sensitive K+ channels. In contrast, in
      hypokalemic rats, insulin caused a pronounced fiber depolarization and reduced
      the residual currents. Our data indicated that in hypokalemic rats, an abnormally
      low activity of ATP-sensitive K+ channel is responsible for the fiber
      depolarization that is aggravated by insulin.

PMID- 9658207
TI  - Activation of soluble guanylyl cyclase by the nitrovasodilator 3
      morpholinosydnonimine involves formation of S-nitrosoglutathione.
AB  - Soluble guanylyl cyclase (sGC) is the major physiological target of sydnonimine
      based vasodilators such as molsidomine. Decomposition of sydnonimines results in
      the stoichiometric formation of nitric oxide (NO) and superoxide (O2-), which
      rapidly react to form peroxynitrite. Inasmuch as sGC is activated by NO but not
      by peroxynitrite, we investigated the mechanisms underlying sGC activation by 3
      morpholinosydnonimine (SIN-1). Stimulation of purified bovine lung sGC by SIN-1
      was found to be strongly dependent on glutathione (GSH). By contrast, GSH did not
      affect sGC activation by NO released from 2,2-diethyl-1-nitroso-oxyhydrazine,
      indicating that NO/O2- released from SIN-1 converted GSH to an activator of sGC.
      High performance liquid chromatography identified this product as the thionitrite
      S-nitrosoglutathione. Further, the reaction product decomposed to release NO upon
      addition of Cu(NO3)2 in the presence of GSH. Activation of sGC was antagonized by
      the Cu(I)-specific chelator neocuproine, whereas the Cu(II)-selective drug
      cuprizone was less potent. Carbon dioxide (delivered as NaHCO3) antagonized S
      nitrosation by peroxynitrite but not by SIN-1. Thus, NO/O2- released from SIN-1
      mediates a CO2-insensitive conversion of GSH to S-nitrosoglutathione, a
      thionitrite that activates sGC via trace metal-catalyzed release of NO. These
      results may provide novel insights into the molecular mechanism underlying the
      nitrovasodilator action of SIN-1.

PMID- 9658208
TI  - Sensitivity to cisplatin and platinum-containing compounds of Schizosaccharomyces
      pombe rad mutants.
AB  - The role of genes that affect response to radiation in determining sensitivity to
      platinum-containing compounds was studied using a panel of 23 strains of the
      yeast Schizosaccharomyces pombe. The radiation-hypersensitive mutants all had the
      same genetic background and most of them contained mutations that disabled either
      cell cycle checkpoints or DNA repair. The tested platinum compounds included
      cisplatin and two complexes containing diaminocyclohexane (oxaliplatin and
      tetraplatin), two ammine/cyclohexylamine complexes with different orientation of
      the leaving groups (JM216 and JM335) and a multinuclear platinum complex (BBR
      3464). The cytotoxic effect of the selected platinum complexes was evaluated by
      using a microtiter growth inhibition assay with a 48 hr exposure to drug. The
      mutants fell into three groups with respect to sensitivity to cisplatin: four
      mutants (rad2, -7, -11, -15) exhibited minimal change in sensitivity; fifteen
      mutants (rad4-6, -8-10, -12-14, -16-17, -19-21, and -22) were 5.1-21.7-fold
      hypersensitive; only rad1 and -3 mutants, defective in checkpoints, and rad18,
      defective in repair, displayed a marked hypersensitivity. None of the mutants
      demonstrated appreciable change in sensitivity to JM216 presumably as a
      consequence of a lack of resistance of the wild-type strain, whereas a moderate
      increase in sensitivity to JM335 was observed for most of the mutants, and
      hypersensitivity to BBR3464 was observed only in rad1 and -3. No relevant changes
      in sensitivity to tetraplatin were observed. Most of the mutants, with the
      exception of rad2, -7, and -15, were hypersensitive to oxaliplatin. These
      findings demonstrate that specific mutations have disparate effects on the
      profile of sensitivity to different members of the same class of cytotoxic
      agents, which provides genetic evidence that different mechanisms are involved in
      differential cytotoxicity induced by Pt compounds. The results also demonstrate
      the utility of such a panel of mutants, constructed on the same genetic
      background, for detecting specific cellular response; presumably, this reflects
      the recognition or processing of specific DNA adducts. In conclusion, because the
      rad1 and rad3 gene products are determinants of cellular response to a large
      number of platinum-containing compounds, the present results support a critical
      role of genes involved in cell cycle control in cellular sensitivity to these
      agents.

PMID- 9658210
TI  - Confidentiality in the editorial process

PMID- 9658209
TI  - A novel benzodiazepine that activates cardiac slow delayed rectifier K+ currents.
AB  - The slowly activating delayed rectifier K+ current, IKs, is an important
      modulator of cardiac action potential repolarization. Here, we describe a novel
      benzodiazepine, [L-364,373 [(3-R)-1, 3-dihydro-5-(2-fluorophenyl)-3-(1H-indol-3
      ylmethyl)-1-methyl-2H- 1,4-benzodiazepin-2-one] (R-L3), that activates IKs and
      shortens action potentials in guinea pig cardiac myocytes. These effects were
      additive to isoproterenol, indicating that channel activation by R-L3 was
      independent of beta-adrenergic receptor stimulation. The increase of IKs by R-L3
      was stereospecific; the S-enantiomer, S-L3, blocked IKs at all concentrations
      examined. The increase in IKs by R-L3 was greatest at voltages near the threshold
      for normal channel activation, caused by a shift in the voltage dependence of IKs
      activation. R-L3 slowed the rate of IKs deactivation and shifted the half-point
      of the isochronal (7.5 sec) activation curve for IKs by -16 mV at 0.1 microM and 
      24 mV at 1 microM. R-L3 had similar effects on cloned KvLQT1 channels expressed
      in Xenopus laevis oocytes but did not affect channels formed by coassembly of
      KvLQT1 and hminK subunits. These findings indicate that the association of minK
      with KvLQT1 interferes with the binding of R-L3 or prevents its action once bound
      to KvLQT1 subunits.

PMID- 9658211
TI  - Drug surveillance: topics for discussion and prospects
AB  - Drug surveillance can be grouped into two areas. The first includes registration
      and inspection, activities that are more familiar to society at large. The second
      involves research and monitoring of adverse effects. Brazilian legislation has
      regulated this subject since 1970. A recent directive also provides for a
      national pharmaceutical surveillance system. This current article provides an
      overview of the history, definitions, pharmacological concepts, classification,
      and diagnosis of the adverse effects of drugs. An analysis is presented of the
      goals and sources of information for drug monitoring as well as some Brazilian
      experience in this field.

PMID- 9658212
TI  - Domestic water use in a rural village in minas gerais, brazil, with an enphasis
      on spatial patterns, sharing of water, and factors in water use
AB  - This paper examines the relationship between domestic water use and
      socioeconomic, environmental, and spatial parameters at the household level in a
      small rural village in northern Minas Gerais State. Five methods are used -
      direct observation, household interviews, self-reporting by households,
      regression analysis, and statistical mapping. Results show that water use is
      characterized by 1) generally low but widely fluctuating values per person per
      day, 2) sharing of water sources between households, 3) the use of multiple
      sources by individual households, 4) avoidance of heavily contaminated stream
      sites, and 5) predominance of socioeconomic factors in water use. Households
      owning their own water supply used, on average, 25.3 liters per person/day and
      those without a supply 9. 0 l, with higher use of the local streams among the
      latter. Water use varied spatially. The socioeconomic factors house quality,
      latrine ownership, type of watersource, and a utility index were significantly
      correlated with water use. Implications of this simple household water sources
      and the more deficient sanitary facilities for potential water-borne disease
      transmission are briefly discussed and suggestions made for further improvements.
      This study confirms the appropriateness of the application of direct observation,
      interview, and microgeographical methods for quantitative water use studies.

PMID- 9658214
TI  - Emergency care costs for victims of violence treated at two hospitals in rio de
      janeiro
AB  - The following is a cost analysis of one month of emergency room treatment
      provided for different types of injuries at two public hospitals in Rio de
      Janeiro. The study focused on the following: 1) costs at each hospital for
      treatment of different injuries (annual and monthly estimates); 2) mean cost of
      each injury; 3) detailed itemized costs of care (materials and drugs, surgery,
      standard procedures, tests, professional fees, and meals). The items were
      investigated at the respective hospitals and included services, materials, and
      resources employed in treating the 1,053 patients included in the sample (498 in
      the Miguel Couto Municipal Hospital - MCMH - and 555 in the Salgado Filho
      Municipal Hospital - SFMH). Traffic accidents (run-over pedestrians, motor
      vehicle collisions, and transportation accidents) accounted for 74.3% of costs at
      MCMH and 48.4% at SFMH. Injuries due to aggression were also considered relevant
      in the cost profile, mainly at SFMH (49% of costs due to violence) as compared to
      24.9% of the total care costs at MCMH. Mean treatment costs for pedestrians run
      over by motor vehicles varied from R$77.76 (SFMH) to R$237.77 (MCMH). Mean
      treatment costs for victims of aggression varied from R$107.35 (SFMH) to R$84.19
      (MCMH). The study suggests public health measures to deal with and prevent
      violence.

PMID- 9658215
TI  - From complaints to impunity: a morbidity and mortality profile of children
      suffering violence
AB  - This article analyzes complaints of violence against children and the procedures
      subsequent to their filing. The methodology, largely qualitative, was two
      pronged, involving an analysis of data from the year 1990 from the police
      precincts in Program Areas 1 and 5 in the city of Rio de Janeiro and a discussion
      on the follow-up of complaints five years after the events. The conclusion was
      that motor vehicle accidents are the most common cause of violence against
      children. Almost no information had been recorded about the circumstances in
      which the violent events occurred. Further, nothing had been done to elucidate
      the perpetrators' liability.

PMID- 9658216
TI  - Premature birth and its repercussions on growth and development in guadalajara,
      jalisco, Mexico
AB  - This study focuses on the repercussions of prematurity for the growth and
      development of newborns from hospitals in Guadalajara, Jalisco, Mexico, typical
      of the health care system in Mexico. Infants were assessed every six months as to
      nutritional status and the Denver Selective Test. In analyzing the results,
      social groups were considered determinant categories for studying prematurity as
      the dependent variable. The results shows that both prematurity and social group
      are risk factors to be considered by the public health field when designing
      health care programs.

PMID- 9658217
TI  - Prevalence of vibrio cholerae O(1) infection in manacapuru, amazonas state,
      brazil (1992)
AB  - This study focused on the prevalence of V. cholerae O(1) infection in 1,196
      individuals living in Manacapuru, Amazonas State, through microtitering of
      vibriocidal antibody and somatic agglutination test. The role of living
      conditions and individual characteristics as possible risk factors for infection
      was also assessed. Vibriocidal titers >/= 1: 40 and/or agglutinating titers >/=
      1: 80 were considered indicators of V. cholerae O(1) infection. Infection
      prevalence was 25.7%. There was no significant statistical difference (p=0.05)
      when analyzed against housing patterns, sanitary facilities, source and treatment
      of water, destination of domestic waste, sex, or profession. Household location,
      number of occupants/household, age, and schooling showed significant statistical
      differences in infection prevalence (p=0.05).

PMID- 9658218
TI  - The relationship between family violence and teenage aggressiveness
AB  - The following is an exploratory study on family violence in two different
      schools, public and the other private, Porto Alegre, Rio Grande do Sul. Seventy
      six families were interviewed, 36 with adolescents classified as aggressive by
      teachers and 40 with non-aggressive adolescents. Total number of subjects was
      213. Physical and severe violence, frequent or occasional, was present in more
      than half of the sample: 41 reports - 53.9%. A third of the cases occurred in the
      private school (37%), with twice as many in the public school (63%). However,
      rates of severe or frequent episodes were similar in both schools. The
      relationship between violent behavior by teenagers and physical punishment by
      parents was significant. That is, aggressive adolescents were punished more than
      non-aggressive ones (odds ratio = 4.3). Prevalence of physical abuse was higher
      in the older, male teenager group, in the presence of sibling aggression, and in
      low-income and dysfunctional families. The study shows that physical abuse is
      more present in society than we would like to imagine.

PMID- 9658219
TI  - A statistical model for defining priority geographic areas for the control of
      neonatal tetanus
AB  - We applied factor analysis to indicators of health and living conditions from
      Brazilian states in order to define geographic areas at potential risk for
      neonatal tetanus. Two factors, namely 'health profile in the rural area' and
      'proportional mortality on neonatal tetanus' were selected and plotted against
      each other. A cluster composed of States from the Northeast plus Para and Amapa
      was found to include most neonatal tetanus risk areas and a low case-reporting
      rate. Another cluster included States from the Southeast and South and displayed
      a neonatal tetanus reporting rate that was compatible with that for other
      indicators. Espirito Santo, however, was found to be a silent productive area.
      The Federal District appeared alone, showing the best health conditions. Finally,
      the States of the Middle West and Roraima constituted the last cluster,
      characterized by intermediate health status and high neonatal tetanus case
      reporting rate. Our results were consistent with the overall Brazilian health
      profile, distinguishing the North and Northeast from the South and Southeast,
      with the Middle West in an intermediate position.

PMID- 9658220
TI  - Restructuring of production and workers' health: a case study
AB  - We performed a case study on a company focusing on the form of management and the
      shop floor workers, in order to identify the possible effects of participant work
      strategies on workers' health. Data on the company included its history, type of
      management, and organization of both production and the work process. Data on
      shop floor workers included age, schooling, perceptions of work, family life,
      recreation, and self-reported disease history. We concluded that the
      characteristics of the management model adopted by the company originated from
      ideas imported from Japan, including flexibilization of production, outsourcing,
      performance of multiple tasks, and participation in the work process. Workers
      referred to participation in the work process in an ambiguous tone. Some reported
      positive effects, like greater freedom and respect, with positive effects on life
      both inside and outside the workplace. For part of the group studied, the
      characteristics of the work organization model practiced in the company had
      negative effects on health, leading them to complain of insomnia, nervousness,
      work-related dreams, and headaches.

PMID- 9658221
TI  - Citizenship, people's participation, and health: beneficiaries of the public
      health services network have their say
AB  - This paper deals with issues of citizenship and people's participation in health
      services, based on an analysis of concepts displayed by a specific group, i.e.,
      users of Primary Care Clinics in Program Area 3.1 in the city of Rio de Janeiro,
      Brazil. The paper analyzes health care users' ideas as the ones most heavily
      influencing the chapter on health in the Brazilian Constitution. The historical
      context is the discussion underway on the role of patients in the relationship to
      professional health care providers, who in turn face the challenge of building a
      'health and hygiene mentality' among the people. Data were gathered through a
      field study using a qualitative social research methodology and identify salient
      points among the ideas of people receiving care. There was a gap (or distortion)
      in their concept of citizenship alongside aspects which, if analyzed according to
      the subjective plane of these social agents, show that they expect channels to be
      created by which they can express their opinions, particularly at the practical
      level. The analysis thus points to the strategic role of day-to-day relationships
      in the social change process and the acquisition of rights, meanwhile seeking to
      shed light on the feasibility of this process in view of the subjectivity of the
      agents giving it life.

PMID- 9658222
TI  - Birth profile for the city of rio de janeiro: a spatial analysis
AB  - This article analyzes the birth profile by neighborhood in the city of Rio de
      Janeiro, using data for 1994 from the Data Base on Live Births. Pattern maps were
      employed in addition to the Moran I statistical test to detect spatial
      clustering. Proportions of live newborns with an Apgar score of 8-10, cesareans,
      mothers with greater than a secondary school education, and teenage mothers
      displayed visually identifiable spatial patterns and significant spatial self
      correlation. Low birth weight displayed a random pattern, indicating that on this
      scale of analysis, this indicator does not distinguish risk groups, despite its
      unquestionable predictive value for child morbidity/mortality at the individual
      level. The Apgar score, despite the high number of non-responses in some
      neighborhoods, showed a pattern more consistent with the distribution of the
      neighborhoods and should thus be used more extensively. The methodology expanded
      the available knowledge on the birth profile in the city, showing potential for
      orienting measures devoted to specific geographic areas.

PMID- 9658223
TI  - Evaluation of the level of knowledge about visceral leishmaniasis in endemic
      areas of Maranhao, brazil
AB  - A prospective study was performed to identify knowledge concerning visceral
      leishmaniasis (VL) in endemic areas of Maranhao, amongst the rural population of
      the Codo township and in a peripheral urban area (an old settlement, Maracana, on
      the outskirts of the city of Sao Luis, and Vila Nova/Bom Viver, Paco do Lumiar
      township). A total of 283 persons were interviewed, including 53 from Maracana,
      103 from Vila Nova/Bom Viver, and 127 from Codo. The sites presented favorable
      conditions for the development and maintenance of VL. Some 93.8% of those
      interviewed had heard of kala-azar. In Maracana, 50.9% referred to sandflies as
      responsible for the transmission of VL, while 87.2% knew that dogs are the main
      link in the epidemiological cycle of the disease. Some 77.8% of those interviewed
      did not know how to control the disease. As regards manifestations of the
      disease, they largely associated it with fever, anemia, weight loss, and an
      enlarged abdomen. Only five individuals knew that Glucantimeis used to treat VL.
      We conclude that knowledge is poor with regard to all aspects of VL in both the
      rural and peripheral urban area.

PMID- 9658224
TI  - An epidemiological profile of drug abuse among elementary and high school
      students in the Cuiaba public school system, brazil, 1995
AB  - A cross-sectional survey was conducted on a sample of 1,061 students to determine
      the epidemiological profile of drug abuse among elementary and high school
      students in the State public school system in Greater Metropolitan Cuiaba, Mato
      Grosso, Brazil, in 1995. Results showed drug abuse among both male and female
      students (27. 2% and 24.1%, respectively). Drug abuse was more common in students
      over 18 years of age (27.1%), with grade/age discrepancies (70.7%), with higher
      classroom absenteeism (44.6%), and with higher social economic levels
      (A+B=34.5%). The most frequently abused drugs among male students were alcohol
      (81.8%), solvents (18.6%), and marijuana (6.0%). Early alcohol abuse was also
      common (12.1 +/-3.6 years). In addition to alcohol (78.6%) and tobacco (29.0%),
      the substances most commonly consumed by students were solvents (14.9%),
      anxiolytics (6. 0%), and amphetamines (4.8%). The 1995 epidemiological profile of
      drug abuse among elementary and high school students in the State public school
      system in Cuiaba was similar data from nationwide surveys conducted in 1987,
      1989, and 1993.

PMID- 9658225
TI  - Blastocystosis in preschool children from bolivar city, venezuela
AB  - To evaluate the prevalence of Blastocystis hominis and its clinical relevance,
      169 preschool children from the 'Los Coquitos' nursery school living in Bolivar
      City, Venezuela, were studied. Stool samples were obtained and examined by direct
      microscopic examination, and the Faust and Willis concentration techniques. Some
      72 of the children had intestinal parasites, of whom 32 (29.09%) had B. hominis.
      Prevalence for the latter was 18.93 % +/- 5.93 %. No differences were observed by
      sex or age (X(2) = 1.84 DF= 3; p > 0. 05). In the majority (53.13%) of the
      children, B. hominis was the only parasite. Giardia lamblia was the parasite most
      frequently identified with B. hominis (39.13%). In 1994, in 12% of the cases more
      than five microorganisms per microscopic field were observed. Clinical
      manifestations were observed in 70.58% of the preschool children. Presence of
      parasites was not correlated with symptomatology, but only with severity. Proper
      clinical and parasitological response to treatment was observed in 80% and 90% of
      patients, respectively. The conclusion was that B. hominis is a relatively
      frequent intestinal parasite among the preschool children evaluated.

PMID- 9658226
TI  - Epidemiological control of tuberculosis in pelotas, rio grande do sul, brazil:
      treatment compliance
AB  - This study assesses risk factors for treatment noncompliance by patients
      registered with the Tuberculosis Control Program who live in the urban area of
      Pelotas, Rio Grande do Sul State. The study lasted from June 1994 to December
      1995. All new cases diagnosed as pulmonary tuberculosis in the 20-80-year age
      bracket were monitored by the Tuberculosis Unit, hub of the tuberculosis control
      program in Pelotas. All patients was monitored from time of diagnosis through end
      of treatment, six months later. Patients answered a standard questionnaire. From
      June 1994 to June 1995, 152 cases were recorded, with some 20% treatment
      noncompliance. We observed no significant association between noncompliance and
      employment status for head-of-family, age, gender, alcoholism, or presence of
      symptoms, while the only risk factor significantly associated with noncompliance
      was non-white skin color, probably due to the study's weak power as a function of
      sample size.

PMID- 9658228
TI  - Self-inflicted violence: a sociological concern and a public health problem
AB  - This paper has two objectives. The first is to reflect on the meaning of suicide
      as a sociological issue, commenting on an article by E.D. Nunes (1988) on the
      famous work by Durkheim. The second is to discuss the same issue within the field
      of public health, analyzing the contributions by the father of sociology and
      approaches by the fields of epidemiology, psychology, psychiatry, and
      psychoanalysis, highlighting the work of Brazilian authors. The paper presents
      information on the Brazilian epidemiological context and concludes by
      demonstrating that only from an analytical point of view can violent causes as a
      whole can be studied separately. Thus, they constantly require epistemological
      and epidemiological surveillance to construct indicators capable of contributing
      to change. This is all the more true because data on current violence need to be
      viewed within the context of the social crisis and changes Brazil is undergoing.

PMID- 9658229
TI  - The socio-cultural impact of the family health program: an evaluation proposal
AB  - This paper develops a critical analysis of the implications of defining the
      family as an object of intervention in health, taking as reference case the
      Family Health Program and proposing an evaluation of its socio-cultural impact.
      As a strategic space for manifestation, confrontation, and therefore observation
      of the health-illness process, the family requires a multidisciplinary approach
      to its structure, dynamics, and behavior in the face of health-related problems,
      determinants, and actions. We present a proposal for assessment of the Family
      Health Program based on the premise that problems and practices in the health
      field are socio-culturally determined.

PMID- 9658230
TI  - Child and adolescent labor: factors, legal aspects, and social repercussions
AB  - Children and youth are currently one of the population segments most heavily
      jeopardized by the worsening of social, economic, and cultural problems in
      Brazil. Factors such as lack of government support for a sound, universally
      accessible school system, income concentration, low wages, unemployment, and
      family dysfunction have direct impacts on the life histories of children and
      adolescents, forcing them to join the labor market early, where their rights as
      'citizens with special developmental conditions' are routinely ignored. This
      article aims to provide support for the eradication of child labor and the
      adaptation of adolescent labor to the terms of the pertinent Brazilian
      legislation. To this end, the article reviews the Federal Constitution,
      Consolidated Labor Laws, and Statute for Children and Adolescents to analyze
      situations in which work activities may or may not be allowed for children and
      adolescents, settling possible points of disagreement between the three legal
      texts and analyzing their social aspects.

PMID- 9658231
TI  - Investigation of a food-borne outbreak in belo horizonte, brasil

PMID- 9658232
TI  - On durkheim, dolly, and others dinosaurs: the museum of grand novelties. A
      contribution to the debate on the article by everardo duarte nunes

PMID- 9658233
TI  - Hepatitis B associated with an alternative therapy centre: look back is extended
      to include hepatitis C.

PMID- 9658234
TI  - Hepatitis B and C in the second issue of Communicable Disease and Public Health.

PMID- 9658235
TI  - [Activity: indicator of quality of health].

PMID- 9658236
TI  - [Strain-gauge plethysmography in angiopathies caused by vibrant tools].
AB  - The authors compare the results obtained from the strain gauge plethysmography on
      79 patients affected by vibrating machines angiopathology with a group of 20
      others non exposed to vibrations. The results, analyzed according to the
      microcirculation vision, lead the authors to suppose that the damage caused by
      vibrating instruments is revealed at the capillary bed trophic exchange level.

PMID- 9658237
TI  - Work and chronic health effects among fishermen in Chioggia, Italy.
AB  - OBJECTIVES: To evaluate whether there is an association between deep-sea fishing
      and common chronic disease. METHODS: The study was cross-sectional,
      simultaneously considering groups of fishermen and non-fishermen. Information on
      life-style and work was collected by means of questionnaires, and clinical data
      were collected by specialists in: Internal Medicine (general clinical
      examination), Cardiology (ECG, measurement of arterial pressure), Pneumology
      (measurement of spirometric volumes), ENT (clinical examination of the ear, nose
      and throat, including audiometry), Ophthalmology (examination of lens). Beside
      the common statistical methods, the logistic stepwise regression analysis was
      used in order to find the risk factors of the diseases, and to correct the risk
      estimates for the confounding variables. RESULTS: Fisherman had prolonged hours
      of continuous work, which were found to be correlated with high cigarette and
      alcohol consumption. Significant associations were found between, on the one
      hand, work accidents, noise-induced hearing loss, solar keratosis, cataracts,
      obstructive bronchitis, rhino-sinusitis, otitis media with tympanic perforation,
      ECG alterations, and, on the other hand, various aspects of fisherman occupation,
      mainly fishing in high sea and work duration as fisherman. CONCLUSION: Deep-sea
      fishing is a stressful and risky work; a reduction in the number of years at sea
      with reduced exposure to noise, poor weather conditions and sun, and a lower
      consumption of cigarettes and alcohol might result in fewer skin, eye respiratory
      and cardiovascular diseases, and injuries.

PMID- 9658238
TI  - The influence of amalgam fillings on urinary mercury excretion in subjects from
      Apulia (southern Italy).
AB  - The purpose of this study was to assess the role of dental amalgams and diet upon
      urinary mercury (U-Hg) excretion. 98 subjects (50 men and 48 women) not exposed
      to inorganic mercury, for either occupational or environmental reasons, and
      living in coastal and inland districts of Apulia (Southern Italy) were
      considered. All the subjects were administered a questionnaire with questions
      concerning life style, medical history, and occupational activity. Dental
      amalgams were evaluated with respect to their number and their surface areas.
      Urinary mercury was measured by the cold vapour atomic absorption technique.
      Expressed in terms of arithmetic mean, U-Hg excretion was found to amount to 1.03
      micrograms/g creatinine (5th and 95th percentile: 0.31 and 2.40; range 0.30
      3.25). Multiple linear regression analysis showed that, of the several tested
      independent variables (dental amalgams, age, body mass index, consumption of
      tuna, bass, swordfish, etc.), only the number of amalgam fillings (T = 5.25; p =
      0.025) and the number of restored surfaces (T = 2.33; p = 0.020) were found
      liable to affect urinary mercury excretion in a significant manner. In
      conclusion, the results of this study confirm the primary role of amalgam
      fillings in affecting urinary mercury excretion in those subjects who are not
      occupationally exposed to inorganic mercury, The resulting urinary mercury levels
      can no doubt be taken as the reference values for the population of Apulia.

PMID- 9658239
TI  - [Use of the Total Quality strategy in the educational process of the occupational
      medicine specialist].
AB  - The formative process of the Occupational physician: a Total Quality approach.
      There is a growing interest in applying the concepts of Total Quality Management
      to the fields of health care and medical education. This paper analyses the field
      of occupational medicine education to explore the relationships of teaching and
      delivering a product or a service. Issues such as defining teaching customers,
      addressing customer's needs, teaching processes, assessing and improving quality
      teaching are described. The occupational physician is requested to act according
      to particular competencies. This implies the need to meet specific requirements.
      To assure the achievement of these goals, the implementation of a teaching
      process must include: (i) targeting the learning objectives (knowledge, skills
      and attitudes the specialist should have), (ii) planning the evaluation system
      (ability of the course to assure the objective achievement), (iii) evaluating the
      curriculum (compliance of the acquired competencies to the needs).

PMID- 9658240
TI  - [Ergonomic evaluation of the physical tasks in "precision fusion" operations].
AB  - In the present paper we performed an "on-site" ergonomic analysis of the work
      tasks in in-plant industrial workers. Specific work cycles have been identified
      and analysed. We measured spatial and temporal parameters of the different
      actions performed by the workers, and we then defined the related risk levels
      according to the internationally accepted guide-lines. The results obtained
      indicate the need of an ergonomic intervention with the aim of providing
      structural changes in the work station.

PMID- 9658241
TI  - [Benzene pollution in the city of Bari].
AB  - The Authors reported data of benzene concentrations obtained in Bari during
      period of time between 1990 and 1995; the measured levels of benzene
      concentrations are not in accord with referent values prescribed by the law,
      mostly always they are exceeded. Present study also discuss problems related to
      gasoline consumption and the number of cars in circulation.

PMID- 9658242
TI  - [Results of motor rehabilitation of patients with pseudobulbar syndrome].
AB  - The aim of this study was to determine whether rehabilitation treatment has a
      real effect on the functional capacity of patients with pseudobulbar syndrome
      (SP), and whether there is any difference in efficacy between rehabilitation
      treatment initiated as early as possible following stroke, compared to treatment
      initiated some months after the last occurrence. We studied 50 SP patients
      divided into three groups according to time passed since the last stroke: group
      1, 20 patients, less than 180 days after stroke; group 2, 30 patients, more than
      180 days after stroke, At the end of the rehabilitation treatment, there was an
      improvement in motility (p < 0.005), functional capacity (p < 0.001) and
      reduction in disability (p < 0.001) only in group 1. We attribute this result to
      the specific pathological substrate of the syndrome and its chronic-progressive
      course, which would seem to hinder the action of compensatory mechanisms involved
      in late recovery.

PMID- 9658243
TI  - [Technical note: proposal of a routine method of accurate measurement of urinary
      trans,trans-muconic acid].
AB  - A method for routine measurement of urinary trans,trans-muconic acid. A method is
      proposed which allows the accurate determination of urinary trans,trans-muconic
      acid (Ma) by HPLC with UV detection. Sample pretreatment consists of a first
      purification on strong anionic exchange (SAX) cartridges followed by extraction
      on "end capped" reversed-phase (C18-EC) ones. Purified samples are directly
      injected onto a chromatographic column (C18, 150 x 4.6 mm I.D., 3 microns) which
      is eluted with water: methanol: acetic acid (97:2:1, v/v) mixture followed by a
      "spike" of acetonitrile. The retention time of MA is 15 min, the coefficient of
      variation is lower than 3%, the limit of detection is 7 micrograms/l. The method
      seems suitable for accurate biological monitoring of subjects exposed to benzene.

PMID- 9658244
TI  - Immunizations for international travel.
AB  - Immunization recommendations for international travelers is a complex subject
      that takes into consideration the geographic destination, planned activities
      during travel, health conditions at destination, length of trip, and underlying
      health status of the traveler. The final immunization program is also determined
      by how much time is available before departure and the worldwide availability of
      vaccines and their cost. In some cases, preventive behaviors and chemoprophylaxis
      may protect against the risk of infection when immunizations are unavailable or
      unobtainable.

PMID- 9658245
TI  - Malaria in travelers. Epidemiology, disease, and prevention.
AB  - The combination of increases in international travel and escalating drug
      resistance has resulted in a growing number of travelers contracting malaria.
      Preventing malaria-associated morbidity and mortality will require improved
      health information for travelers about the risk of malaria and appropriate
      preventive measures, improved recognition of infection by physicians, rapid and
      accurate laboratory diagnosis, and prompt initiation of effective therapy.

PMID- 9658246
TI  - Travelers' diarrhea. Epidemiology, prevention, and self-treatment.
AB  - Risk factors for travelers' diarrhea include adventurous behavior, consumption of
      unclean water or food, and special hosts like those taking long acting H2
      blockers. Approaches to prevention include education about risk factors, which
      often fails to lead to modification of risky behavior, and chemoprophylaxis with
      bismuth subsalicylate-containing compounds or antimicrobial agents.
      Chemoprophylaxis is generally discouraged except in special circumstances and in
      high-risk hosts. Self-treatment of travelers' diarrhea is successful in limiting
      the course of diarrhea and minimizing losses of vacation and business time.
      Current therapeutic options, in order of increasing effectiveness, include
      attapulgite, BSS-containing compounds, loperamide, antimicrobial agents such as
      the fluoroquinolones, and the combination of loperamide and an antimicrobial
      agent. Under study are a nonabsorbed antimicrobial agent, rifaximin, and a novel
      calmodulin inhibitor, zaldaride. Development and evaluation of vaccines against
      enterotoxigenic Escherichia coli and Shigella are proceeding apace but are not
      yet available for routine use.

PMID- 9658247
TI  - Prevention of common travel ailments.
AB  - An understanding of the subjects covered in this article is significant in
      keeping travelers healthy and comfortable. Each section covers a range of
      problems and suggestions for their prevention. The areas that are reviewed are:
      1) fitness to fly; 2) problems in transit; 3) altitude sickness; 4) marine and
      swimming hazards; 5) insect precautions; 6) pre- and posttravel care; and 7)
      illness abroad. An effort has been made to provide practical recommendations as
      in many cases there is little data and no rules, thus the travel health advisor,
      with the patients' input, will need to determine the best course of action for
      each individual and itinerary.

PMID- 9658249
TI  - Travel with infants and children.
AB  - The risks faced by children traveling internationally may be minimized by
      providing and applying advice about comfort, safety, skin protection, and food
      and water hygiene. Prior to travel, children should be current on standard
      immunizations and may receive several specialized vaccines. Antibiotics for the
      presumptive treatment of travelers' diarrhea are usually indicated, and malaria
      chemoprophylaxis may be safely administered even to young children. Evaluation
      and care following prolonged stays in foreign countries can decrease the burden
      of imported disease.

PMID- 9658248
TI  - The pregnant traveler.
AB  - The care of the pregnant traveler is both challenging and rewarding. It requires
      clinical information and skills that are derived from many disciplines. This
      article reviews preparatory guidelines for safe travel by the pregnant mother and
      her most important travel companion, the developing fetus. Issues considered are
      pretravel risk assessment, immunizations, and prevention of travelers' diarrhea
      and hepatitis. The safety and efficacy of malaria chemoprophylaxis in the present
      context of widespread multidrug-resistant malaria is discussed, and guidelines
      are offered for both prevention and treatment. A safety profile of commonly used
      travel medications, antibiotics, and antiparasitic drugs is reviewed.

PMID- 9658250
TI  - The compromised traveler.
AB  - Compromised travelers represent a diverse and challenging group of individuals.
      They include HIV-infected patients who are at risk for potentially adverse
      reactions to immunizations, and new exposures to enteric water-borne
      opportunistic pathogens associated with chronic infections. Such travelers may
      encounter unfamiliar opportunistic fungi and classical tropical infections, such
      as leishmaniasis, whose pathogenesis can be enhanced by the presence of prior HIV
      infection. Other immunocompromised groups include those who are functionally or
      anatomically asplenic, and patients who are iatrogenically immunosuppressed from
      medications utilized for solid organ transplantation, chemotherapy, or treatment
      of malignancies. This population of travelers also includes those with diabetes
      mellitus who may require adjustments in their dosing, administration, and
      possibly even the types of insulin used on their trips. These patients are also
      at greater risk for acquisition of tuberculosis, severe community-acquired
      pneumonia, urinary tract infections, and pyomyositis. Older travelers present
      both the infectious disease and travel medicine specialist with issues such
      events, malignancy-related infections, myocardial infarction, and other forms of
      cardiopulmonary compromise, which the authors address in this article.

PMID- 9658251
TI  - The sexual health of travelers.
AB  - Sex and travel do not infrequently coincide as pleasurable occupations. This
      articles explores the possible risks of unsafe sexual activity in a travel
      related context, gives guidelines on how to decrease risks for both partners, and
      outlines how to manage the exposed or infected traveler on his or her return
      home. Both sexually transmitted infections and contraception are covered.

PMID- 9658252
TI  - Screening returning travelers.
AB  - Posttravel screening is the clinical and laboratory assessment of an individual
      aimed at uncovering occult infections, pathology, or health risks, the treatment
      of which will yield a significant health benefit to the individual. Screening
      must be tailored to the different risk patterns associated with different travel
      categories (e.g., missionary, tourist). Screening, predominantly a secondary
      prevention strategy, is most cost-effective when integrated with primary
      prevention strategies aimed at preventing future travel related illness (Table
      6). The screening process begins with a medical history that allows a definition
      of risks and a tailored approach to laboratory tests. The screening tests
      currently available for STDs, tuberculosis, and parasitic infections have been
      reviewed, and although cost-effectiveness data are not available for most post
      travel screening tests, recommended approaches are proposed. Traditionally,
      screening has been directed at uncovering occult infectious disease (STDs,
      tuberculosis, and parasitic infections). Important benefits can be gained,
      however, by including screening questions and tests for those diseases that are
      the major causes of mortality, both in nontraveling and in traveling North
      Americans, that is, the atherosclerotic and neoplastic diseases and trauma,
      especially vehicular.

PMID- 9658253
TI  - Fever in the returned traveler.
AB  - The most important cause of fever in the returned traveler is malaria. All
      febrile patients in which malaria is epidemiologically possible require urgent
      evaluation for P. falciparum malaria, which can be rapidly fatal in the nonimmune
      patient. Early diagnosis and therapy can prevent severe morbidity and mortality.
      Other less common causes of undifferentiated fever include acute schistosomiasis,
      the enteric fevers, rickettsial diseases, leptospirosis, and dengue fever. Early
      empiric therapy for suspected leptospirosis and the rickettsial infections is
      encouraged to decrease morbidity and mortality. About a quarter of febrile
      patients do not have an etiologic agent determined for their illness but recover
      without sequelae. Patients with fever and hemorrhagic manifestations within 3
      weeks of their return need to be isolated for the remote possibility of a highly
      transmissible agent. Although the febrile traveler is always a challenge, the
      real world differential diagnosis is limited and a systematic approach via the
      history, physical examination, and selected laboratory tests is usually
      sufficient to confirm the diagnosis or eliminate potentially serious infections.

PMID- 9658254
TI  - Skin problems in the traveler.
AB  - Skin lesions are common in travelers and include a mix of mundane dermatologic
      problems and rare diseases acquired only in remote or tropical regions. The
      morphology, distribution, and progression of the lesions are useful in assessing
      possible causes. Early in the evaluation it is important to determine whether the
      patient might have a process that is rapidly progressive, treatable, or
      transmissible. In addition to routine laboratory studies, biopsy and serologic
      tests are often necessary to confirm a specific diagnosis.

PMID- 9658255
TI  - Persistent diarrhea in the returned traveler.
AB  - In conclusion, the causes of chronic diarrhea in the returned traveler are
      protean. Careful evaluation requires an understanding of where the traveler has
      been, when they were there, the type of diarrheal illness, medications taken, and
      knowledge of the patients' other medical problems. Protozoa, particularly G.
      lamblia, C. parvum, and C. cayatenensis, are among the more commonly identified
      agents. If the patient is immunocompromised, microsporidia and Isospora become
      more likely, and a prior history of antimicrobial use raises the possibility of
      C. difficile colitis. Occasionally helminths, which establish intimate contact
      with the intestinal mucosa, may also cause prolonged diarrhea. If these and other
      gastrointestinal insults, such as tropical sprue, small bowel overgrowth, lactose
      intolerance, and processes unrelated to travel are excluded by more invasive
      studies or clinical history, the patient can be reassured that idiopathic chronic
      diarrhea is usually self-limited.

PMID- 9658256
TI  - Eosinophilia in the returning traveler.
AB  - Eosinophilia is one of the most common laboratory abnormalities seen in the
      returning traveler. Although elevations in peripheral eosinophil levels can occur
      in a wide variety of disease processes, worldwide, helminth parasites are the
      major group of infectious agents responsible for eosinophilia. While often
      directed at helminth infections in their early stages of clinical evolution, the
      approach to the evaluation of the returning traveler with eosinophilia must
      consider the many causes of eosinophilia including those not casually related to
      travel. This article reviews the major parasitic causes of eosinophilia and
      provides a systematic approach to the evaluation of eosinophilia following
      travel.

PMID- 9658257
TI  - The ethnic minority traveler.
AB  - Although the ethnic minority traveler is exposed to the same risks as other
      travelers, there are special considerations that make them vulnerable to certain
      diseases. In addition, many ethnic minority travelers are traditionally
      underserved by the medical community and often travel without the benefit of
      adequate counseling and immunization. The specific disease entities covered in
      this article include parasitic diseases (e.g. malaria, trypanosomiasis,
      intestinal helminths), tuberculosis, and other respiratory diseases, dengue, and
      sexually transmitted diseases and HIV.

PMID- 9658258
TI  - Keeping current. Travel medicine resources available on the Internet.
AB  - As travel medicine practices expand and multiply, practitioners increasingly need
      to be familiar with constantly changing disease epidemiology and drug resistance
      patterns in over 220 different countries. Nowadays, keeping current means
      utilizing the wide array of resources available on the internet. This article
      contains background information on the most relevant travel medicine-oriented
      Internet sites and provides their universal resource locators in a convenient
      table.

PMID- 9658259
TI  - Vascular dementia: dead or alive?
AB  - The term 'Vascular Dementia' remains popular as a diagnostic entity, since it
      encompasses a variety of vascular pathologies. This is in stark contrast to many
      clinical classificatory systems that weight their definitions strongly towards
      stroke alone. A diagnosis of vascular dementia is complicated by compounding
      factors that reduce both the validity and specificity of diagnostic systems. This
      review highlights some of the problems faced in epidemiological, clinical,
      neuropathological and radiological studies attempting to define a clear-cut
      syndrome of dementia associated with cerebrovascular disease. The role of non
      stroke ischaemia is also discussed. It is concluded that the term vascular
      dementia may have outlived its usefulness as a valid concept; alternative
      approaches are suggested.

PMID- 9658260
TI  - The mini-mental state examination, will we be using it in 2001?

PMID- 9658261
TI  - Mini-mental and son.

PMID- 9658262
TI  - An informant interview for the diagnosis of dementia and depression in older
      adults (IDD-GMS).
AB  - BACKGROUND: There has been no instrument developed for the differential diagnosis
      of psychiatric conditions using an informant. The present study describes the
      development and validation of an informant interview for the diagnosis of
      dementia and depression in older adults (IDD-GMS). The IDD-GMs, as its name
      indicates, is based upon the well-established Geriatric Mental State Schedule
      (GMS). METHOD: Thirty older adults with psychiatric illnesses were identified. An
      informant/career was interviewed using the IDD-GMS. Questions from the GMS were
      altered to reflect the informant nature of interview. Validity was compared to
      ICD-10 diagnoses. Interrater reliability was determined. RESULTS: Using a
      hierarchical diagnostic system, receiver operating characteristics demonstrated
      one optimal cutpoint for sensitivity, > 13 for dementia and > 16 for depression,
      and one for specificity, > 13 for dementia and > 10 for depression. CONCLUSION:
      The validity and reliability of the IDD-GMS falls within acceptable limits and
      indicates that the IDD-GMS can be used as a diagnostic instrument for dementia
      and depression. The IDD-GMS represents the first informant interview to achieve
      this.

PMID- 9658263
TI  - Psychosocial factors associated with the use/non-use of mental health services by
      primary carers of individuals with dementia.
AB  - The study investigated psychosocial factors associated with the use/non-use of
      services by primary carers of people with dementia (caring for relative/friend
      with dementia). The factors considered were individual differences, health,
      stress, family/social support, years of caring, age of carers/person with
      dementia, gender and level of behavioural disturbance presented by the person
      with dementia. The participants were referred to the study by health services,
      social services representatives and GPs. The carers (N = 50) were divided into
      two groups (service user/non-user). The findings indicated that primary carers in
      the non-user service group scored significantly higher on a measure (sense of
      coherence; SOC) estimating an individual's ability to deal with stressful
      situations. The individual's ability to deal with caring responsibilities was
      associated with a reduction in the level of diagnosable psychiatric disorder or
      'caseness' and the non-use of services. None of the other factors considered were
      found to be significantly different between the two career groups. However, a
      significant inverse association between health, stress and individual ability to
      deal with stressful situations was found when the two career groups were
      combined.

PMID- 9658264
TI  - Does post-traumatic stress disorder occur after stroke: a preliminary study.
AB  - BACKGROUND AND PURPOSE: Psychological reactions after stroke have been recognized
      for some time. The present study examined whether psychological symptoms
      consistent with post-traumatic stress disorder (PTSD) could occur after stroke as
      a consequence of the sudden and unpredictable occurrence of a life-threatening
      internal stressor. METHODS: Sixty-one patients who had experienced a first-ever
      stroke or transient ischaemic attack were assessed using standard self-report
      clinical measures for anxiety, depression and PTSD. Those patients who fulfilled
      criteria on at least one PTSD self-report measure were subsequently assessed
      using a structured clinical interview for PTSD. RESULTS: Six (9.8%) patients
      fulfilled criteria for PTSD. No significant differences were found between the
      post-stroke PTSD group and the non-PTSD group in terms of premorbid health and
      lifestyle, or experiences of adverse life events. Significant differences were
      noted with respect to self-reported post-stroke mental health and premorbid
      neuroticism. The post-stroke PTSD group also scored consistently higher on
      measures of anxiety, depression and psychiatric caseness. CONCLUSIONS: The
      results of this study demonstrate a number of close similarities between post
      stroke PTSD and classical PTSD. We therefore conclude that PTSD or a PTSD-like
      syndrome can occur after stroke.

PMID- 9658265
TI  - Younger people with dementia: diagnostic issues, effects on carers and use of
      services.
AB  - OBJECTIVE: To determine difficulties experienced by carers of younger people with
      dementia. DESIGN: Cross-sectional questionnaire survey. PARTICIPANTS: 102
      eligible carers of persons less than 65 years of age with dementia, recruited
      through support groups and clinicians' referrals. MAIN OUTCOME MEASURES: Problems
      with diagnostic process; professionals/services consulted; psychological,
      physical, occupational and financial impact of illness on carers and children;
      use of and satisfaction with services. MAIN RESULTS: Diagnostic problems were
      reported by 71% of carers. Mean time until diagnosis was 3.4 years (SD 2.8) after
      consulting 2.8 (1.4) professionals. Carers reported frustration (81%) and grief
      (73%). Adverse psychological effects were common, more so in female than male
      carers (p < 0.01). The younger the carer, the more psychological and physical
      effects were experienced (p < 0.01). Only 8% of carers considered that their
      children had encountered no problems because of the dementia. Of 61 working
      carers, 59% reduced their hours or stopped working after diagnosis, and 89% of
      all carers had experienced financial problems subsequent to diagnosis. Most
      carers (89%) had used a support service, but 25% had never used community
      support, 32% had never used respite. Proportions of carers rating services as
      good ranged between 43 and 100%. CONCLUSIONS: Younger people with dementia, and
      their carers, face difficulties in obtaining a diagnosis. Carers also experience
      psychological problems, financial worries, loss of employment and family
      conflict, and their children are affected. Most carers had used services, but
      some dissatisfaction existed.

PMID- 9658266
TI  - Assessment of progression and prognosis in 'possible' and 'probable' Alzheimer's
      disease.
AB  - OBJECTIVE: The objective of this study was to assess the rate of progression and
      clinical predictors of decline in subjects with possible and probable Alzheimer's
      disease (AD). DESIGN/SETTING: The annual rate of change (ARC) for
      cognitive/functional scales was calculated for 95 subjects with AD attending a
      memory clinic. Two consecutive ARCs were calculated for a subgroup of 39
      subjects. RESULTS: The ARCs were relatively normally distributed; however, there
      was a large degree of variability. Neither age nor duration of symptoms at
      presentations were predictive of the rate of decline. However, the data suggested
      an effect of gender, with males having a greater rate of decline in cognition (p
      = 0.02). Finally, the rate of progression over the first year did not predict the
      subsequent ARC (p = 0.25). CONCLUSIONS: The high variability in ARCs observed in
      this study and poor correlation between consecutive ARCs suggest that neither
      mean ARC values nor the previous rate of decline can be used to aid clinicians in
      the assessment of response to acetylcholinesterase inhibitors or other specific
      treatments for AD.

PMID- 9658267
TI  - Concurrent validity of the GMS-AGECAT (A3) package in a Danish nursing home
      population.
AB  - AIM: To validate the Danish version of the GMS-AGECAT (A3), the Standardized Mini
      Mental State Examination (SMMSE) and the Geriatric Depression Scale-15 (GDS-15)
      by comparing them to clinical ICD-10 criteria in a Danish nursing home
      population. METHODS: With a participation of 91%, the study included 100
      residents. All residents were interviewed with the GMS-AGECAT (A3), SMMSE and GDS
      15 by an MD and then blindly diagnosed by a consultant geriatric psychiatrist.
      All residents approached for an interview were included, also those who were not
      able to communicate (the non-accessibles). RESULTS: The prevalence of clinical
      psychiatric ICD-10 main diagnoses was 56%. The non-accessibles had significantly
      higher psychiatric morbidity and lower ADL scores (modified Barthel ADL index)
      compared to those who were able to communicate. With the non-accessibles (N =
      100) included, the optimal screening and diagnostic cutpoint for the GMS-AGECAT
      organic diagnoses was 2/3, with 96% sensitivity, 73% specificity, 77% predictive
      value of a positive test and 95% predictive value of a negative test. The SMMSE
      and GDS-15 had better screening properties compared to the GMS-AGECAT but only
      60% of the residents were able to complete the SMMSE and 78% were able to
      complete the GDS-15. CONCLUSION: The Danish version of the GMS-AGECAT has
      relevant diagnostic and screening properties for organic disorders in Danish
      nursing home populations.

PMID- 9658269
TI  - Current awareness in geriatric psychiatry.

PMID- 9658268
TI  - Serotonin syndrome following the administration of tramadol with paroxetine.

PMID- 9658270
TI  - Do consultant home visits have a future in old age psychiatry?

PMID- 9658272
TI  - The validity of psychometric instruments for detection of dementia in the elderly
      general population.
AB  - OBJECTIVE: To compare the validity of different instruments for screening and
      diagnosis of dementia and to provide threshold scores for these purposes, ie
      screening focusing on a high sensitivity and diagnosis focusing on a high
      specificity. SETTING: 287 subjects from a general population sample who had
      completed more than one of these psychometric tests. METHODS: The performances of
      the Structured Interview for the Diagnosis of Dementia of the Alzheimer Type,
      Multi-Infarct Dementia and Dementias of Other Aetiology according to ICD-10 and
      DSM-III-R, the Mini-Mental State Examination, the Blessed Dementia Rating Scale,
      the Global Deterioration Scale, the Verbal Fluency Test, the Word list Learning
      Task, the Trail Making Test and the Labyrinth Test were compared using receiver
      operating characteristics analysis. RESULTS: The validity of composite
      instruments for the discrimination of dementia and cognitive health was higher
      than the validity of individual tests. However, some cognitive tests, ie verbal
      fluency and immediate recall of words, reached a high validity, making them
      useful and short screening instruments for dementia. CONCLUSION: There is no
      perfect instrument for screening and diagnosis of dementia. Different threshold
      scores for different purposes were provided in the present study. Recommendations
      for improving the validity of the Delayed Word List Learning Task for
      discriminating dementia and cognitive health include the expansion of list length
      and shortening of delay.

PMID- 9658271
TI  - Depressive symptoms of Alzheimer caregivers are mainly due to personal rather
      than patient factors.
AB  - OBJECTIVES: To investigate the predictors of caregiver's depressive symptoms in a
      sample of community-dwelling Alzheimer's patients. DESIGN: A cross-sectional
      study was conducted in an Alzheimer's unit specifically devoted to the care of
      demented patients in Brescia Province (Italy). One hundred and three dyads were
      consecutively recruited between July 1994 and July 1995. Caregivers were
      sons/daughters (65%) or husbands/wives; mean age was 54.6 +/- 13.2. Alzheimer's
      patients Mini Mental State Examination score was 11.3 +/- 8.3; patients were
      equally distributed among disease severity levels. The following variables have
      been collected: (a) background and context variables (caregiver's age, gender,
      marital status, education, relationship and cohabitation with the patient,
      employment status, satisfaction with household income);(b) caregiver's personal
      resources (health, social relationships and social interactions, formal supports
      use, assistance and vigilance); (d) primary stressors (patient's age and gender,
      cognitive status, functional status, frequency of behavioural disturbances).
      Caregiver's depressive symptoms represented the main outcome measure. RESULTS:
      Being husband or wife, low self-rated health and caregiving competence, high
      numbers of hours for assistance and patient's behavioural disturbances and
      younger age were associated caregiver's depressive symptoms. With multivariate
      analysis only relationship to the patient, caregiver's health and competence were
      independent predictors of caregiver's depressive symptoms. CONCLUSION: Factors
      related to the caregiver--relationship, health and competence--rather than to the
      patient constitute the main risk factors for caregiver's depressive
      symptomatology.

PMID- 9658273
TI  - CANDID--Counselling and Diagnosis in Dementia: a national telemedicine service
      supporting the care of younger patients with dementia.
AB  - OBJECTIVES: To audit and evaluate the introduction of a novel support service for
      younger people with dementia, their families and the professionals caring for
      them. DESIGN: A retrospective review of all calls received by a telephone
      helpline over a 2-year period. SETTING: CANDID (Counselling and Diagnosis in
      Dementia) offers direct access, by telephone and e-mail, to specially trained
      nurse/counsellors who record the caller's query, provide emotional support and
      practical advice. In addition to general advice, clinical details are held for
      patients registered with the service so that the advice given can be tailored to
      the patient's specific need and routed via the general practitioner for action.
      Advice is reviewed by a consultant neurologist and psychiatrist. SUBJECT: Callers
      to the CANDID helpline, who made a total of 1,121 calls. MAIN OUTCOME MEASURES:
      Details of the caller and of the patient they were caring for. Reason for calling
      and advice given to the caller RESULTS: Of the 1,121 calls received during the
      first 2 years of operation, 547 were 'registered' calls relating to 241
      individual patients where more specific advice could be given through the GP. The
      remaining 574 'generic' calls were from members of the public and healthcare
      professionals who had heard about the service and were seeking information and
      advice. Reasons for calls were divided into three broad categories: general
      information; clinical advice; and advice on social issues. Among the registered
      callers, 50% of calls were for clinical advice. Letters were sent to GPs on 67
      occasions; 48 (56%) provided information only for the GP, 16 (24%) advised a
      secondary referral and eight (12%) advised on the use of specific medication.
      CONCLUSION: The service has become rapidly accepted and used by families of
      patients and members of the public. Healthcare professionals have made less use
      of the service than anticipated, but it is hoped that this will increased as
      information about the service becomes disseminated.

PMID- 9658274
TI  - A preliminary report: a new scale to identify the pseudodementia syndrome.
AB  - BACKGROUND: The literature was reviewed to abstract items which were claimed to
      distinguish organic dementia from pseudodementia. Their discriminating powers
      were tested in a prospective study. Eighteen of these items were selected to
      create a questionnaire which should distinguish organic dementia from
      pseudodementia. The gold standard was the final diagnosis given by a consultant
      psychiatrist 12-14 months later. METHOD: One hundred and twenty-eight patients
      referred to our service with a differential diagnosis of depressive
      pseudodementia were screened using a checklist of 44 characteristic features (in
      the form of questions with 'yes' or 'no' answers) which were claimed in the
      literature of differentiate between organic dementia and depressive
      pseudodementia. This checklist covers the areas of history, clinical data,
      insight and performance. RESULTS: Forty points (questions) out of the 44 in the
      checklist showed significant discriminating power to differentiate dementia from
      depressive pseudodementia (p < 0.01). A principal component and factor analysis
      was performed from which 18 questions were extracted. The shortened questionnaire
      was able to classify (43/44 cases) 98% of dementia cases and (60/63) 95% of
      depression correctly. A new definition has been introduced for 'pseudodementia'
      as a syndrome of reversible subjective or objective cognitive problems caused by
      non-organic disorder. Thus depressive pseudodementia may be classified into two
      subtypes. Type I is a group of patients who have depressive symptoms with subject
      complaint of dysmnesia without measurable intellectual deficits. Type II is a
      group of patients who have depressive symptoms and show poor cognitive
      performance based on poor concentration not due to organic disorder.

PMID- 9658275
TI  - Cognitive impairment in late life schizophrenia: a suitable case for treatment?
AB  - The benign side-effect profiles of the atypical antipsychotic drugs have earned
      them an important niche in old age psychiatry. Evidence for a specific
      improvement in cognitive function associated with the use of these drugs is
      inconsistent and the definitive studies are still awaited. If these drugs can
      improve cognitive function in elderly patients with schizophrenia and
      schizophrenia-like psychosis, then in terms of patient-years of effective
      treatment of cognition, this action may be more significant than the treatment of
      Alzheimer's disease with cholinergic therapies.

PMID- 9658276
TI  - Assessment of patients with memory problems using a nurse-administered instrument
      to detect early dementia and dementia subtypes.
AB  - BACKGROUND: With the development of pharmacological treatments for Alzheimer's
      disease there will be an increase in the numbers of patients requiring assessment
      from specialist services. Could the role of the specialist clinician be supported
      by other health professionals screening those who might benefit from treatment?
      METHOD: Sixty-four consecutive referrals to the Leicester University Memory
      Clinic were assessed at home by a community psychiatric nurse using a semi
      structured interview. The nurse then reported her findings to a psychiatrist and
      a diagnosis was agreed. This diagnosis was then compared to the Memory Clinic
      diagnosis and a standardized (ICD-10) diagnosis recorded by another psychiatrist
      examining the clinic records. RESULTS: The nurse assessment procedure performed
      well in detecting dementia, with a kappa statistic (k) of 0.75 when compared to
      the standardized and Memory Clinic diagnoses. There was, however, only moderate
      concordance between the ICD-10 diagnosis and nurse (k = 0.46) and the Memory
      Clinic and nurse (k = 0.60) for Alzheimer's disease. The relatively low k value
      for Alzheimer's disease was principally a result of difficult in differentiating
      vascular dementia. CONCLUSIONS: A single supervised community psychiatric nurse,
      using a structured assessment instrument, can adequately detect early dementia in
      a sample of patients referred with memory problems. Subtypes of dementia are not,
      however, accurately differentiated.

PMID- 9658277
TI  - Prevalence and clinical correlates of psychotic symptoms in Alzheimer's disease.
AB  - Psychotic symptoms occur commonly in Alzheimer's disease (AD), predict a more
      rapid rate of cognitive decline and increase the risk of aggressive behaviour.
      Seventy patients with probable AD, recruited from an old age psychiatry service,
      were assessed to determine the prevalence and clinical correlates of delusions
      and hallucinations. Psychiatric symptoms were measured using the Behavioural
      Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD), Hamilton Rating Scale
      for depression (HRSD) and the Depressive Signs Scale (DSS). Thirty-four per cent
      of the sample experienced delusions and 11% hallucinations in the previous month.
      Men were more likely than women to have experienced psychotic symptoms. Psychotic
      and non-psychotic groups did not differ in age, age at illness onset, dementia
      severity, HRSD or DSS scores. This study confirms the high prevalence of
      psychotic symptoms in AD patients encountered in clinical practice, and suggests
      that psychosis and depression represent independent behavioural disturbances in
      AD.

PMID- 9658278
TI  - Evaluation of three aggression/agitation behaviour rating scales for use on an
      acute admission and assessment psychogeriatric ward.
AB  - BACKGROUND: In recent years many instruments measuring aggressive and agitated
      behaviours among the elderly in a variety of settings have emerged. Individual
      instruments have only occasionally been compared with each other. METHOD: Some
      psychometric properties of three aggression/agitation scales on an acute
      assessment and admission psychogeriatric ward were examined. The correlation
      between the Rating Scale for Aggressive Behaviour in the Elderly (RAGE), the
      Cohen-Mansfield Agitation Inventory (CMAI) and the Brief Agitation Rating Scale
      (BARS) and their internal consistencies and test-retest and interrater
      reliabilities were measured. RESULTS: The RAGE was strongly correlated with the
      CMAI (rho = +0.73) and the BARS (rho = +0.72). The CMAI was strongly correlated
      with the CMAI (rho = +0.84). The internal consistency, as measured by Cronbach's
      alpha, was greater than 0.8 on all three scales. The test-retest and interrater
      reliability correlations were 0.75 or greater for all three scales (except the
      BARS interrater reliability correlation of 0.6). CONCLUSIONS: All three scales
      have good psychometric properties for use in acute admission assessment
      psychogeriatric wards.

PMID- 9658280
TI  - Current awareness in geriatric psychiatry.

PMID- 9658279
TI  - SSRI discontinuation syndrome treated with fluoxetine.

PMID- 9658281
TI  - Calretinin in pretecto- and olivocerebellar projections in the chick:
      immunohistochemical and experimental study.
AB  - Calretinin (CaR) is a calcium-binding protein that is distributed extensively in
      the central nervous system. It is localized in the cell bodies and neurites of
      specific neuronal populations and serves, therefore, as a reliable anatomical
      marker. Some components of the pretectocerebellar projection, which connects
      specific pretectal nuclei to caudal cerebellar folia, are concerned with the
      cerebellar control of visual reflexes. We investigated the distribution of
      pretectocerebellar-projecting neurons in relation to cells that show CaR
      immunoreactivity. Cells that project to the cerebellar cortex in the diencephalic
      primary visual nuclei and in other grisea, like the nucleus spiriformis medialis
      and the nucleus dorsofrontalis, colocalized with those that appeared to be
      immunolabeled intensely with anti-CaR antiserum. To explore the hypothesis of a
      common developmental origin of these pretectal cerebellopetal neurons, we also
      investigated the development of CaR-immunopositive cells in the chick pretectum
      and the arrival of their fibers in the cerebellum, from 10 days of incubation
      (stage 36) to posthatching stages. Finally, we analyzed the source of CaR+
      climbing fibers and found a subpopulation of CaR+ cells in the inferior olivary
      nucleus. On the whole, these results suggest that there is a common developmental
      origin of pretectal cerebellopetal neurons, some of which share the property of
      CaR expression. The functional significance of this correlation needs to be
      investigated.

PMID- 9658282
TI  - Nicotinic acetylcholine receptors in rat cochlear nucleus: [125I]-alpha
      bungarotoxin receptor autoradiography and in situ hybridization of alpha 7 nAChR
      subunit mRNA.
AB  - The cochlear nucleus (CN) is the first site in the central nervous system (CNS)
      for processing auditory information. Acetylcholine in the CN is primarily
      extrinsic and is an important neurotransmitter in efferent pathways thought to
      provide CNS modulation of afferent signal processing. Although muscarinic
      acetylcholine receptors have been studied in the CN, the role of nicotinic
      receptors has not. We examined the distribution of one nicotinic acetylcholine
      receptor subtype, the alpha-bungarotoxin receptor (alpha Bgt), in the CN.
      Quantitative autoradiography was used to localize receptors and in situ
      hybridization was used to localize alpha 7 mRNA in CN neurons that express the
      alpha Bgt receptor. Binding sites for alpha Bgt are abundant in the anterior
      ventral, posterior ventral, and dorsal divisions of the CN, and receptor density
      is low in the granule cell layer and interstitial nucleus. Heterogeneity in CN
      subregions is described. Four distinct patterns of alpha Bgt binding were
      observed: (1) binding over and around neuronal cell bodies, (2) receptors locally
      surrounding neurons, (3) dense punctate binding in the dorsal CN (DCN) not
      associated with neuronal cell bodies, and (4) diffuse fields of alpha Bgt
      receptors prominent in the DCN molecular layer, a field underlying the granule
      cell layer and in the medial sheet. The perikaryial receptors are abundant in the
      ventral CN (VCN) and are always associated with neurons expressing mRNA for the
      receptor. Other neurons in the VCN also express alpha 7 mRNA, but without alpha
      Bgt receptor expression associated with the cell body. In general, alpha Bgt
      receptor distribution parallels cholinergic terminal distribution, except in
      granule cell regions rich in cholinergic markers but low in alpha Bgt receptors.
      The findings indicate that alpha Bgt receptors are widespread in the CN but are
      selectively localized on somata, proximal dendrites, or distal dendrites
      depending on the specific CN subregion. The data are consistent with the
      hypothesis that descending cholinergic fibers modulate afferent auditory signals
      by regulating intracellular Ca2+ through alpha Bgt receptors.

PMID- 9658283
TI  - Tumor-suppressor p53 is expressed in proliferating and newly formed neurons of
      the embryonic and postnatal rat brain: comparison with expression of the cell
      cycle regulators p21Waf1/Cip1, p27Kip1, p57Kip2, p16Ink4a, cyclin G1, and the
      proto-oncogene Bax.
AB  - The tumor-suppressor protein p53 has been implicated in cell cycle arrest and
      apoptotic cell death in dividing cells (Yonish-Rouach et al. [1991] Nature
      352:342-347. To elucidate possible functions of p53 in the regulation of cell
      division and cell death during development of the rat central nervous system, we
      compared the spatial and temporal expressions of p53 mRNA and protein with those
      of its transcriptional targets Bax, p21Waf1, and cyclin G1 and with the cyclin
      dependent kinase inhibitors p27Kip1, p57Kip2, and p16Ink4a. From embryonic day 14
      until the second postnatal week, p53 mRNA and protein were found predominantly in
      proliferating zones, including the cells of the emerging external granular layer
      of the cerebellum, and the ventricular and the subventricular zones of the
      forebrain. At all postnatal ages, there was a high expression of p53 mRNA and
      protein in cells of the rostral migratory stream, a well-defined pathway along
      which precursor cells of olfactory interneurons migrate from the ventricular and
      subventricular zones toward the olfactory bulb. In addition to its expression in
      proliferating cell populations, p53 was expressed in postmitotic cells of the
      cerebral cortex and hippocampus at embryonic and early postnatal stages. p53,
      p27Kip1, p16Ink4a, and bax alpha mRNA colocalized in the ventricular and
      subventricular zones at embryonic and early postnatal stages, but the
      distribution of p53 differed from that of its transcriptional targets cyclin G1
      and p21Waf1 and from that of the cyclin-dependent kinase inhibitor p57Kip2, which
      were predominantly expressed in fully differentiated neurons. Double-labeling
      studies showed that p53 mRNA and protein were absent in cells undergoing
      developmental cell death, as identified by the presence of single- or double
      stranded nuclear DNA breaks. Protein levels of p53 decreased during development
      in all brain areas studied. These results indicate a role for p53 in the control
      of cell division and early differentiation rather than in the control of cell
      death during rat brain development. The nonoverlapping temporal and spatial
      expression patterns of p53 and its transcriptional targets Bax, cyclin G1 and
      p21Waf1 suggest that each of these gene products fulfill independent roles in
      brain morphogenesis.

PMID- 9658284
TI  - Concomitant expression of genes encoding integrin alpha v beta 5 heterodimer and
      vitronectin in growing parallel fibers of postnatal rat cerebellum: a possible
      role as mediators of parallel fiber elongation.
AB  - External granule cells in the premigratory zone and the upper molecular layer of
      neonatal rat cerebellum elongate their neurites (parallel fibers) bidirectionally
      before and during migration into the internal granular layer. In the present
      study, it is shown that integrin alpha v beta 5 heterodimer (INT alpha v beta 5)
      is expressed in parallel fibers in these layers at postnatal days 3-20, but not
      in migrating granule cells or mature parallel fibers. Vitronectin (VN), the
      dominant ligand for INT alpha v beta 5, was concomitantly detected in the
      premigratory zone and the upper molecular layer during this period. Several other
      subunits including alpha 1-6 and beta 1-4 were not detected. When granule cells
      were prepared from postnatal cerebella and cultured for a few days, the parallel
      fibers elongated well in response to VN, but the granule cells did not migrate on
      VN. This fiber elongation was specifically inhibited by both anti-INT alpha v
      beta 5 antibody and peptides containing Arg-Gly-Asp (RGD), a sequence responsible
      for cell adhesion mediated by VN. Neither control integrin antibody against
      integrin alpha v beta 3 heterodimer nor control peptides containing Arg-Gly-Glu
      (RGE) showed an inhibitory effect on fiber elongation. These observations
      strongly suggest that the INT alpha v beta 5 VN receptor plays a role in the
      elongation of parallel fibers from granule cells during cerebellar histogenesis,
      but its expression is not required for their maintenance or granule cell
      migration. INT alpha v beta k could be considered as a new marker of parallel
      fibers during cerebellar development.

PMID- 9658285
TI  - Terminal dendritic sprouting and reactive synaptogenesis in the postnatal organ
      of Corti in culture.
AB  - Synaptogenesis in the organ of Corti between the primary receptors, the inner
      hair cells, and the peripheral processes of their afferent spiral ganglion
      neurons in the mouse lasts for 5 days postnatally (Sobkowicz et al. [1986] J.
      Neurocytol. 15:693-714). The transplantation of the organ into culture at the
      fifth postnatal day induces a reactive sprouting of dendritic terminals and an
      extensive formation of new ribbon synapses within 24 hours. This reactive
      synaptogenesis differs strikingly from the primary synaptogenesis and has been
      seen thus far only in the inner hair cells. The synaptically engaged neuronal
      endings sprout a multitude of filopodia that intussuscept the inner hair cells.
      The filopodial tips contain a heavy electron-dense matter that appears to attract
      the synaptic ribbons, which form new synaptic contacts with the growing
      processes. The intensity of the filopodial growth and synaptogenesis subsides in
      about 3 days; the filopodia undergo resorption, leaving behind fibrous
      cytoplasmic plaques mostly stored in the supranuclear part of the hair cells.
      However, occasional filopodial growth and formation of new synaptic connections
      continued. The data demonstrate that any disruption or disturbance of the initial
      synaptic contacts between the inner hair cells and their afferent neurons caused
      by transplantation results in prompt synaptic reacquisition. Furthermore, we
      suggest that the transitory phase of terminal sprouting and multiribbon synapse
      formation manifests a trophic dependence that develops postnatally between the
      synaptic cells.

PMID- 9658286
TI  - Receptor autoradiographic mapping of the mesial motor and premotor cortex of the
      macaque monkey.
AB  - This study analyzes regional and laminar distribution patterns of
      neurotransmitter binding sites in the motor areas of the macaque mesial frontal
      cortex. Differences in distribution patterns are compared with the
      cytoarchitectonic parcellation. Binding sites were analyzed with quantitative in
      vitro receptor autoradiography in unfixed brains of five macaque monkeys. Alpha
      amino-3-hydroxy-5-methyl-4-isoxalone propionic acid (AMPA), kainate, and N-methyl
      D-aspartate (NMDA) binding sites were labeled with [3H]AMPA, [3H]kainate, and
      [3H]MK-801, respectively, muscarinic binding sites with [3H]pirenzepine or
      [3H]oxotremorine-M, noradrenergic binding sites with [3H]prazosin or [3H]UK
      14304, gamma-aminobutyric acid (GABA)A binding sites with [3H]muscimol, and
      serotoninergic binding sites with [3H]ketanserine. Adjacent sections were stained
      with a modified Nissl method for cytoarchitectonic analysis. In the motor areas
      F1, F3, and F6, [3H]AMPA, [3H]pirenzepine, and [3H]oxotremorine-M binding was
      maximal in layers II, III, and V, and [3H]kainate binding was maximal in layers V
      and VI. Clear-cut changes in laminar distribution patterns of [3H]AMPA,
      [3H]kainate, and [3H]oxotremorine-M binding sites very closely matched
      corresponding cytoarchitectonic borders. Mean areal binding densities of all
      ligands to F1, F3, and F6 were plotted as polar plots for each area. A polygon
      was obtained for each area ("neurochemical fingerprint") when all the density
      values belonging to one area were connected with each other. The "neurochemical
      fingerprints" of F1, F3, and F6 were virtually identical in shape but increased
      in size from F1 to F6. This result reflects the functional similarity of these
      motor-related areas and possibly correlates with their differential involvement
      in motor control. Areas F1, F3, and F6 can thus be grouped into one
      "neurochemical family" of areas.

PMID- 9658287
TI  - Distribution of the voltage-dependent calcium channel alpha(1A) subunit
      throughout the mature rat brain and its relationship to neurotransmitter
      pathways.
AB  - The alpha(1) subunit provides both the voltage-sensing mechanism and the ion pore
      of voltage-dependent calcium channels. Of the six classes of alpha(1) subunit
      cloned to date, alpha)1A) is the subject of debate in terms of its functional
      correlate, although it is generally thought to encode voltage-dependent calcium
      channels of the omega-agatoxin IVA-sensitive, P/Q type. In the present study, an
      alpha(1A)-specific riboprobe and antibody were used with in situ hybridisation
      and immunohistochemical techniques to localise alpha(1A) messenger ribonucleic
      acid transcripts and subunit protein throughout the mature rat brain. Dual
      localisation of alpha(1A) protein and markers for acetylcholine, catecholamines,
      and 5-hydroxytryptamine have also been performed in a number of discrete areas.
      Abundant and widespread distribution of alpha(1A) protein was found, with
      immunoreactivity occurring both in cell bodies and as punctate staining in areas
      of neuronal processes. Several associations were noted across alpha(1A)
      localisation, defined neuroanatomical regions, and neurotransmitter systems.
      However, alpha(1A) expression was not confined to loci corresponding to any one
      neurotransmitter type, although a high level of expression was observed in
      cholinergic neurones. The distribution of the alpha(1A) subunit in the rat
      corresponded well with the limited human mapping data that are available.

PMID- 9658288
TI  - Identification of motor neurons to the circular muscle of the guinea pig gastric
      corpus.
AB  - The projections of enteric neurons to the circular muscle of the guinea pig
      gastric corpus were investigated systematically by using the retrogradely
      transported fluorescent carbocyanine dye 1,1'-didodecyl-3,3,3',3'-tetramethyl
      indocarbocyanine perchlorate (DiI), applied to the muscle layer or myenteric
      plexus in vitro. DiI-labeled motor neuron cell bodies were located up to 6.3 mm
      aboral, 17 mm oral, and up to 20 mm circumferential to the DiI application site.
      Labeled nerve fibers ran for long distances from the DiI application site toward
      the greater and lesser curvatures, where they coursed parallel to the bundles of
      the "gastric sling" muscle. The majority of labeled cells were located toward the
      lesser curvature of the stomach. Nerve cell bodies that were aboral to the DiI
      application site were usually small, immunoreactive for choline
      acetyltransferase, and, thus, were likely to be excitatory motor neurons. Neurons
      that were located orally were larger, fewer in number, and immunoreactive for
      nitric oxide synthase and, thus, were likely to be inhibitory motor neurons.
      Application of DiI directly to the myenteric plexus filled neurons up to 15 mm
      aborally and up to 21 mm orally but labeled few neurons circumferentially. All
      nerve cells that were filled from either the circular muscle or the myenteric
      plexus had Dogiel type I morphological features. These results demonstrate a
      clear polarity of projection of inhibitory and excitatory motor neurons and a
      functionally continuous innervation of the circular and gastric sling muscle
      layers. Nonmotor neurons in the myenteric plexus were demonstrated, but neurons
      with Dogiel type II morphological features are apparently absent.

PMID- 9658289
TI  - Choline acetyltransferase expression during a putative developmental waiting
      period.
AB  - The relationship between the cholinergic expression, morphological development,
      and target cell innervation of olivocochlear (OC) efferent neurons was
      investigated in the postnatal hamster. Similar to what was found in previous
      studies, tracer injections into the contralateral cochlea labeled cells bodies
      retrogradely in periolivary regions and labeled cell bodies only rarely in the
      lateral superior olive (LSO). Few morphological differences were found among cell
      bodies labeled between postnatal day 1 (P1) and P30. Tracer injections into the
      crossed OC bundles within the brainstem anterogradely labeled terminals below the
      inner hair cells of the cochlea prior to P5 and labeled terminals below outer
      hair cells after P5, consistent with a period of transient innervation, as
      hypothesized previously. Within the superior olive, choline acetyltransferase
      (ChAT) was expressed differentially. In periolivary regions, ChAT was expressed
      as early as P0. ChAT-immunoreactive cell bodies in periolivary regions were
      similar morphologically to retrogradely labeled OC neurons. In contrast, within
      the LSO, ChAT was not expressed until after P2. Consistent with a medical OC
      projection to the cochlea at early postnatal ages, ChAT immunoreactivity was
      detected below inner hair cells as early as P2 but was not detected below outer
      hair cells until after P6. Our results suggest that medial OC neurons not only
      provide transient connections to inner hair cells but also may express ChAT when
      they are below inner hair cells. Furthermore, these results raise the possibility
      that OC neurons may be capable of acetylcholine synthesis and release prior to or
      simultaneous with their innervation of the cochlea.

PMID- 9658290
TI  - Radiation awareness program for extracorporeal shockwave lithotripsy using
      Medstone lithotripters.
AB  - To determine the effectiveness of a radiation awareness program in reducing the
      radiation exposure to patients treated by a Medstone lithotripter, the exposure
      was calculated at the end of each extracorporeal shockwave (SWL) treatment using
      a table of measurements of the estimated entrance exposure rates 70 cm from the X
      ray tube port. The results, related to stone size and patient weight, were
      distributed every month to each radiologic technologist, and a summary was sent
      regularly to the treating urologists. The doses before and after the introduction
      of the radiation awareness program were compared to determine the effectiveness
      of the program, and the chi-square test was used to determine statistical
      significance. The average calculated radiation exposure before and after
      introduction of the radiation awareness program was 16.39 rad and 8.26 rad,
      respectively, for patients with single renal stones; 17.31 rad and 9.02 rad,
      respectively, with single ureteral stones; 18.45 rad and 9.39 rad, respectively,
      with multiple renal stones; and 20.59 rad and 11.28 rad, respectively with
      multiple ureteral stones. These reductions in calculated radiation exposure were
      statistically significant only with multiple ureteral stones (P = 0.03). The only
      statistically significant differences in the stone-free rates, retreatment rates,
      and post-SWL secondary procedure rates before and after the introduction of the
      radiation awareness program were seen in the stone-free rates with single renal
      stones: 70% v 65%, respectively (P = 0.02); in the retreatment rates with single
      ureteral stones: 10% v 6%, respectively ( P < .01); and in the post-SWL secondary
      procedure rates with single renal stones: 4% v 2%, respectively (P = 0.01), and
      single ureteral stones: 7% v 4%, respectively (P = 0.05). The radiation awareness
      program resulted in a 51% reduction in the estimated radiation exposure to
      patients during SWL using Medstone lithotripters.

PMID- 9658291
TI  - Lipid peroxidation induced by shockwave lithotripsy.
AB  - To determine the relation between high-energy shockwaves (HESW) and the presence
      of lipid peroxidation produces, juvenile pigs were subjected to shockwave
      lithotripsy (SWL). After lithotripsy, both treated and control kidneys were
      analyzed, along with urine samples collected before, during, and after SWL.
      Thiobarbituric acid-reactive substance (TBARS) and lipid-conjugated diene (CD)
      concentrations, used as markers for membrane lipid peroxidation, were determined
      in the kidney and urine samples. Significantly increased mean TBARS
      concentrations (146%) were associated with homogenates of lithotripsy-treated
      kidneys, 77.8 +/- 14.4 (SD) mmol/g v the controls, 31.4 +/- 14.9 mmol/g.
      Lithotripsy induction of lipid peroxidation products in the cortex, the gross
      damage site, and the respective medulla were also examined. In HESW-treated
      cortex samples, increased TBARS concentrations were seen--75.0 +/- 21.3 mmol/g-
      compared with untreated controls-- 45.2+/- 5.6 mmol/g--while increased CD
      concentrations (168%) were observed in the medulla of HESW-treated samples. No
      significant differences were observed in TBARS or CD concentrations in urine
      samples from control or treated kidneys, yet specific lipid hydroperperoxides
      were detected in the urine of HESW-treated kidneys. We conclude that HESW
      lithotripsy of swine kidneys is associated with increased lipid peroxidation
      products that may cause further cellular damage. Lipid peroxidation induced by
      SWL may be one of several mechanisms that lead to other potential bioeffects.
      Finally, analysis of specific lipid hydroperoxides in the urine of HESW-treated
      kidneys may serve as a noninvasive marker of renal injury after clinical SWL.

PMID- 9658292
TI  - Pneumatic v electrokinetic lithotripsy in treatment of ureteral stones.
AB  - Recently, a new device (Combilith) for electrokinetic lithotripsy (EKL) has
      become available which is very similar to the well-known device for pneumatic
      (ballistic) lithotripsy (Swiss Lithoclast). The Lithoclast uses air pressure to
      push a projectile within the handpiece against the end of a metal probe, which is
      thereby accelerated and thrown like a jackhammer against the stone. In principle,
      the same stroking movement of a small metal probe is provided by EKL; the
      difference is that instead of a projectile, a magnetic core within the handpiece
      is accelerated by the electromagnetic principle. This paper compares the clinical
      efficacy and the features of the two devices. Testing the devices on a stone
      model, taking into account stone propulsion, the systems turned out to equally
      effective regarding stone disintegration. However, stone displacement was more
      pronounced with the Lithoclast applied on easily breaking stones. In a second
      experiment, an optoelectronic movement-measuring apparatus (Zimmer camera) was
      employed to measure the range and velocity of the movement of the probe tip
      without any contact. The linear acceleration velocity ranged from 5 to a maximum
      of 12.5 m/sec with both systems, but the maximum height of the stroke was 2.5 mm
      with the Lithoclast and 1 mm with EKL. After the initial break-up of soft stones,
      further impact of the probe tip against the stone resulted merely in propulsion;
      thus, the greater probe stroke height is the cause of the stone displacement. In
      a clinical trial, 22 ureteral stones were treated with the Lithoclast and 35 with
      the EKL. The two devices were equally effective in terms of stone disintegration
      and safety margin. Fixation using a Dormia basket was necessary in 12 cases (8
      Lithoclast, 4 EKL). Although a difference in probe stroke height was noted when
      comparing pneumatic and electrokinetic lithotripsy, there were no clinically
      significant differences in the efficacy of stone fragmentation or stone-free
      rates. At the current time, EKL is less costly.

PMID- 9658293
TI  - Cost effectiveness of electrohydraulic lithotripsy v Candela pulsed-dye laser in
      management of the distal ureteral stone.
AB  - To compare the efficacy, safety, and cost of the Candela laser lithotripter with
      those of the electrohydraulic (EHL) lithotripter in the management of distal
      ureteral stones, 24 patients with obstructing stones were randomized to laser
      lithotripsy or EHL. Ureteroscopy was performed with a 6.9F ACMI Miniscope under
      general anesthesia. Twelve patients were treated with laser lithotripsy using the
      Candela Air-Cooled MDL 2000 LaserTripter System with a 200-micron pulsed-dye
      laser fiber. Twelve patients were treated with the Herzog Electrohydraulic
      LithoTripter using the 1.9F fiber. The following issues were studied: stone-free
      rates, complications (intraoperative, postoperative, and late), and costs of the
      procedure. No difference was found in the stone-free or complication rates. One
      patient was found to have hydronephrosis at 6 months secondary to an unrelated
      proximal ureteral stone. There was no difference in the efficacy of laser
      lithotripsy and EHL in the management of distal ureteral stones, but EHL was
      found to be significantly more cost effective: the cost for EHL was +336 per
      case, whereas, the cost for lasertripsy was +4220 per case, a greater than 10
      fold difference.

PMID- 9658294
TI  - Holmium laser lithotripsy for ureteral calculi: an outpatient procedure.
AB  - A retrospective review was conducted to evaluate the efficacy of ureteroscopic
      lithotripsy using the holmium laser with a semirigid endoscope in a newly
      established day surgery center. In 1996, 69 consecutive patients (40 male and 29
      female) with a mean age of 46.7 (range 21-73) years and ASA status I or II
      underwent ureteroscopic lithotripsy for their ureteral calculi using the holmium
      laser (365-micron fiber; power setting 0.5-1.4 J/5 Hz) and 8.5F semirigid
      ureteroscope in a day surgery setting. Stone features, postoperative pain scores,
      readmissions, and complications were evaluated. Eighteen upper, 17 middle, and 34
      lower ureteral stones were treated, with a mean size measuring 12.1 (5-45) mm.
      The mean operative time was 61 minutes including the anesthetic time (range 15
      150 minutes), and the success rate was 91% (63/69). The complication rate was 10%
      (7/69) including four unscheduled readmissions (6%). Telephone follow-up on
      postoperative Day 1 and Day 3 revealed mean pain scores of 2 and 1, respectively
      (on a 0-10 scale) and an analgesic requirement of 1 tablet of Dologesic
      (containing 32.5 mg of dextropropoxyphene + 320 mg of paracetamol) four times a
      day on both days. Ureteroscopic lithotripsy using the holmium laser and a
      semirigid endoscope is highly successful and well tolerated and carries a low
      complication rate. It is indicated as an ambulatory and minimally invasive
      treatment modality in low-risk patients with ureteral stones.

PMID- 9658295
TI  - Stone fragmentation pattern of piezoelectric shockwave lithotripsy in vitro.
AB  - Whole stones (N = 64; largest diameter 5-15 mm) were treated in vitro with
      piezoelectric shockwaves using the Edap LT-01 lithotripter with 2.5 Hz at either
      100% or 54% power. The number of fragments larger than 2 mm was counted after
      every 30 seconds. The stones were defined as totally broken when all fragments
      were < 2 mm. Total fragmentation time was correlated with the energy level and
      the size of the stone. The number of large fragments did not correlate with the
      energy level but rather with the original size of the stone.

PMID- 9658296
TI  - Percutaneous management of benign adrenal cysts: a treatment option in selected
      cases.

PMID- 9658297
TI  - Is laparoscopic radical nephrectomy with specimen morcellation acceptable cancer
      surgery?
AB  - Laparoscopic radical nephrectomy (LRN) for renal-cell carcinoma (RCF) with
      removal of the specimen by morcellation and suction remains controversial because
      precise pathologic tumor staging is lost, and there is a risk of tumor seeding.
      We assessed the theoretical impact of surrendering precise pathologic staging on
      the management of patients with low-stage RCC (T3a or less). In 22 patients who
      underwent open radical nephrectomy for RCC, the preoperative CT-based clinical
      stage was correlated with pathologic tumor staging. Possible clinical inclusion
      criteria for LRN were then correlated with pathologic tumor staging. When
      comparing clinical and pathologic staging, one patient was understaged and seven
      were overstaged by preoperative CT. However, if clinical stage T3a or lower was
      used as the inclusion criterion for LRN, 19 patients (86%) would have been so
      treated, none would have been underassigned, and future management would not have
      been compromised according to pathologic staging. Management of patients with low
      stage RCC relying on clinical staging only is oncologically adequate. This would
      make LRN an acceptable option for this subset of patients.

PMID- 9658298
TI  - Laparoscopic management of ureteral perforation during ureterolithotripsy.
AB  - The author presents a case of successful laparoscopic repair of a ureteral
      perforation happening during ureterolithotripsy (URS). The perforation of the mid
      ureter was managed by a retroperitoneal approach: the stone from the
      retroperitoneum was removed, a double-J stent was inserted up to the kidney, the
      perforation opening was sutured, and the retroperitoneum was drained. The patient
      healed without any complication. Similar management of a ureteral perforation has
      not been found in the literature.

PMID- 9658299
TI  - Laparoscopic subcapsular nephrectomy.
AB  - A 26-year-old patient with end-stage renal disease secondary to vesicoureteral
      reflux and recurrent pyelonephritis was referred for bilateral native
      nephrectomy. A transperitoneal laparoscopic approach was used. Extremely dense
      fibrosis was encountered around the left kidney during the dissection. A left
      laparoscopic subcapsular nephrectomy and a right extracapsular nephrectomy were
      performed. The indications and surgical technique for laparoscopic subcapsular
      nephrectomy are discussed.

PMID- 9658300
TI  - Laparoscopic ureteroureterostomy using vascular closure staples in porcine model.
AB  - The greatest difficulty in performing a laparoscopic pyeloplasty is the suturing
      of the ureteropelvic junction. The purpose of this study was to evaluate the use
      of nonperforating titanium vascular closure staple (VCS) clips to perform in
      laparoscopic ureteroureterostomy in the porcine model. Six female minipigs
      underwent laparoscopic transection of one of the proximal ureters at the level of
      the lower pole of the kidney. Ureteroureterostomy was then performed using the
      titanium VCS clips. The animals were evaluated at 6 and 12 weeks
      postureteroureterostomy with retrograde pyelography and differential creatinine
      clearances. At 12 weeks, the animals were euthanized, and the area of
      ureteroureterostomy was examined grossly and histopathologically. The technique
      for laparoscopic vascular clipping of the ureteroureterostomy proved to be fast
      and effective. Follow-up indicated that the method was successful in producing a
      functionally patent anastomosis. No encrustation, stone formation, or
      intraluminal clip was noted in any of the ureters or kidneys undergoing the
      ureteroureterostomy. The area of the ureteroureterostomy showed minimal fibrosis
      and inflammation on histopathologic examination. In this animal study, the
      nonperforating titanium clips facilitated the performance of a laparoscopic
      ureteroureterostomy.

PMID- 9658301
TI  - Electromotive drug administration and hydrodistention for the treatment of
      interstitial cystitis.
AB  - Thirteen patients with interstitial cystitis diagnosed by the NIH criteria were
      treated with intravesical electromotive administration of lidocaine and
      dexamethasone followed by cystodistention. After a mean follow-up of 10 (range 3
      22) months, 8/13 (62%) of the patients reported complete resolution of bladder
      symptoms lasting an average 4.5 (range 0.75-17) months. Partial or short-term
      improvement of bladder symptoms was observed in three patients, while two
      patients reported aggravation of pain for several days after therapy. A
      significant increase in bladder capacity, to an average 166% of the pretreatment
      capacity, was observed in all patients. Whenever symptoms recurred after
      initially effective therapy, retreatments were performed with equal efficacy in
      11 patients. This promising new therapeutic approach, performed on an outpatient
      basis, may become first-line treatment for patients with interstitial cystitis.

PMID- 9658302
TI  - Role of the trigone in micturition.
AB  - The exact function of the trigone in the act of micturition is not yet known. The
      current communication discusses its role. The myoelectric activity of the urinary
      bladder and trigone was studied in nine volunteers (six women, three men; mean
      age 38.6 +/- 9.9 years) using Beckman suction electrodes. Two electrodes were
      applied to the bladder and one to the trigone. The EMG and vesical pressure were
      recorded before and during vesical filling and voiding. Slow waves or pacesetter
      potentials (PPs) were recorded at rest from the detrusor and trigone. They had
      regular frequency and were followed randomly by bursts of action potentials
      (APs). The frequency and amplitude of the trigonal PPs and APs were significantly
      lower than those of the vesical tissue. The mean PP frequency was 5.8 +/- 1.8
      cycle/min (cpm) and amplitude 0.69 +/- 0.1 mV in the bladder and 3.4 +/- 1.2 cpm
      (P < 0.05) and 0.36 +/- 0.09 mV (P < 0.05), respectively, in the trigone. During
      vesical filling, neither the vesical pressure nor the vesical and trigonal PPs
      and APs registered significant differences from the resting stage (P > 0.05).
      During voiding, the vesical electric activity increased and presented as fast
      activity spikes or APs of high amplitude (mean 678.6 +/- 88.6 muV). The trigonal
      electric activity showed no significant change (P > 0.05) in comparison with the
      pre-evacuation status. These findings suggest that the trigone does not contract
      during voiding, thus refuting the claim that the trigone is responsible for
      preventing ureterovesical reflux on voiding.

PMID- 9658303
TI  - Holmium laser resection of the prostate.
AB  - A total of 35 patients with benign prostatic hyperplasia (BPH) were treated with
      the Ho: YAG laser using a new technique termed holmium laser resection of the
      prostate or HoLRP. The laser energy was applied directly to prostatic tissue
      exclusively through the use of a standard 550 micron end-firing fiber. A high
      powered holmium laser was used and was set at 2.4 J per pulse at 25 pulses per
      second for an average power of 60 W. The mean preoperative AUA Symptom Score was
      24. Postoperatively, the score dropped to 10.9, 8.2, 5.2, and 4.6 at 1 week, 1
      month, 3 months, and 6 months, respectively. The peak urine flow rate improved
      from 6.3 mL/sec preoperatively to 15.1, 15.3 and 16 mL/sec at 1 week, 1 month, 3
      months, and 6 months. A foley catheter was removed within 24 hours of completion
      of the operation in 31 patients (89%), and voiding was improved. The HoLRP
      technique was bloodless, and the short-term results were satisfactory. Most
      importantly, the defect produced by HoLRP is identical to that of a conventional
      transurethral resection. These initial results demonstrate that HoLRP is a useful
      surgical alternative in the treatment of patients with obstructive BPH.

PMID- 9658304
TI  - Early endoscopic realignment as primary therapy for complete posterior urethral
      disruptions.
AB  - We assessed the outcome of early endoscopic realignment of posterior urethral
      disruptions. We evaluated six patients who underwent early or delayed endoscopic
      realignment for the disrupted posterior urethra over a 3-year period. C-Arm
      fluoroscopy guidance and orientation in two planes were used as necessary.
      Potency, restructure rates, and continence were assessed in addition to hospital
      length of stay, intraoperative blood loss, and uroflow. The collective results of
      ten publications were also reviewed. In the present study, all of the six
      patients were continent. One had diminished erectile capability, and four
      required subsequent internal urethrotomies. Evaluation of the cumulative data
      (including the present study) showed an overall 9% incontinence rate, 60% potency
      rate, and 54% restricture rate. Endoscopic realignment of the disrupted posterior
      urethra is a minimally invasive procedure with results comparable to those of
      open delayed urethroplasty. Early and delayed repairs have been applied with
      similar results, the former being advocated in patients who are medically and
      orthopedically stable. Hospital stay, loss of work, morbidity, and related
      complications are also markedly decreased with early endoscopic realignment.

PMID- 9658305
TI  - Influence of decay of laser fibers during laser prostatectomy on clinical
      results.
AB  - Three types of sidefiring laser fibers (34 Urolase, 20 Ultraline, and 114 Prolase
      II) were visually inspected after a laser prostatectomy, and transmission
      measurements were performed using a power meter (Aquarius). The results were
      correlated with the clinical outcome. Despite differences in the amount of loss
      in transmission for the fibers used, we could not establish any significant
      effect on clinical outcome measures, such as improvement in maximal flow rate or
      symptom score. The visual aspect of the Urolase fibers was significantly related
      to the amount of transmission loss, whereas no such relation was found for the
      other two types of fibers. Prostate size and the total amount of energy delivered
      by the laser source also did not correlate with the clinical outcome. To
      determine the relation between the energy absorbed by the prostate and clinical
      outcome, a large number of patients must be evaluated, and any factor that can be
      controlled needs to be monitored. For the latter, the power meter as presented
      here is a useful complementary tool.

PMID- 9658306
TI  - Effects of transjugular intrahepatic portosystemic shunt (TIPS) on esophageal
      motor function and gastroesophageal reflux.
AB  - The effects of transjugular intrahepatic portosystemic shunt (TIPS) placement on
      esophageal motor function and gastroesophageal reflux were investigated in
      patients with esophageal varices. In six men with esophageal varices, esophageal
      manometry and upper gastrointestinal endoscopy were performed before and 15-20
      days after TIPS placement. Intraesophageal pH monitoring was performed in the
      four patients with severe esophageal varices (defined as the largest sized
      varices) following TIPS placement. Findings were compared with those in six
      healthy men (controls) who underwent esophageal manometry and intraesophageal pH
      monitoring. The esophageal varices resolved or were reduced after TIPS placement.
      Resting lower esophageal sphincter (LES) pressures were similar in the study
      group before and after TIPS placement and in the control subjects. The incidence
      and progression of esophageal contractions were similar in the study group before
      and after TIPS placement and in the control subjects. At 3 cm above the LES, the
      amplitude of esophageal contraction after TIPS placement was significantly higher
      than that before TIPS placement. At 3 and 8 cm above the LES, the amplitude of
      esophageal contraction in the control subjects was significantly higher than that
      in the study group before and after TIPS placement. Esophageal acid exposure time
      after TIPS placement was similar to that in the controls. TIPS placement is a
      useful treatment that improves esophageal motor function without the occurrence
      of pathologic gastroesophageal reflux.

PMID- 9658307
TI  - Electrogastrographic power ratio in humans is not related to changes in antrum
      skin distance but to antral motility.
AB  - It is not clear whether the power increase in electrogastrography (EGG) after
      meal or water ingestion reflects increases in gastric motility or gastric
      distension bringing the stomach closer to the electrodes on the abdominal skin
      surface. We recorded EGG and real-time ultrasonography simultaneously before and
      after 150-ml water ingestion in 17 healthy volunteers. We calculated gastric
      power, by spectral analysis of EGG by the maximum entropy method, for 400 s
      before and after water ingestion, and calculated their ratio (power ratio). We
      calculated, using sonography, the number of antral contractions before and after
      water ingestion, the motility index after water ingestion, the distance between
      the antrum and the abdominal skin surface before and after water ingestion, and
      the ratio of these distances (distance ratio). The number of contractions was
      positively correlated with gastric power before water ingestion, and the antrum
      skin distance was negatively correlated with gastric power both before and after
      water ingestion. The motility index after water ingestion was positively
      correlated with both gastric power after water ingestion (Spearman's rank
      correlation r = 0.492; P = 0.0498) and the power ratio (r = 0.615; P = 0.0141).
      There was no correlation between the distance ratio and the power ratio. These
      results suggest that the power increase in EGG induced by water ingestion does
      not reflect the approach of the antrum to the abdominal surface, but rather,
      reflects antral motility after water ingestion.

PMID- 9658308
TI  - Hydrogen peroxide-induced cellular injury is associated with increase in
      endogenous fluorescence from rat gastric mucosal epithelial cell culture: A new
      method for detecting oxidative cellular injury by fluorescence measurement.
AB  - To develop a new method of detecting cellular injury caused by oxygen radicals,
      we studied endogenous fluorescence from the cultured cells of a rat gastric
      mucosal epithelial cell line. Measurement with an ultra-high sensitivity camera
      image processor system under an inverted epifluorescence microscope showed that
      the fluorescence intensity of the cells increased time- and dose-dependently
      after the addition of hydrogen peroxide (H2O2), an oxygen radical precursor, to
      the medium. This increase was inhibited by the presence of catalase. Phase
      contrast and fluorescence microscopy revealed that the fluorescence was emitted
      from granular substances in the cytoplasm of the injured cells. The spectral
      pattern of excitation and emission indicated that the fluorescent substances were
      flavins. In cell-free experiments, glutathione reductase which has flavin adenine
      dinucleotide (FAD) at the active site, increased in fluorescence after incubation
      with H2O2 in the presence of reduced glutathione and glutathione peroxidase.
      These findings indicate that FAD in the cytoplasm of cells injured by H2O2
      increased in endogenous fluorescence according to the extent of injury, and
      suggest that fluorescence measurement may be a simple method in cellular
      toxicology to detect oxygen radical-induced injuries.

PMID- 9658309
TI  - Type IIa early gastric cancer with proliferation of xanthoma cells.
AB  - We report a type IIa early gastric cancer associated with xanthoma cell
      proliferation in a 61-year-old man. The patient was admitted to our hospital
      because of a gastric polyp detected at a medical checkup. An irregular protruding
      lesion with xanthoma cell proliferation was detected endoscopically. Histological
      examination showed a well differentiated tubular adenocarcinoma in the mucosa
      associated with xanthoma cell proliferation. The distribution of the xanthoma
      cells in the stroma corresponded closely with that of the cancer cells. Neither
      atypism nor mitotic figures were recognized in the xanthoma cells. In an
      immunohistochemical study, almost all the xanthoma cells were stained positive
      for alpha 1-antitrypsin, while relatively few exhibited positive S-100 protein
      staining. Specific monocyte chemotactic and activating factor immunoreactivity
      was present only in the xanthoma cells, and not in the cancer cells. On the basis
      of these findings, it was speculated that the gastric cancer cells may have
      caused the xanthoma cell proliferation via an autocrine mechanism i.e., by a
      chemical mediator acting in a paracrine or juxtacrine manner.

PMID- 9658310
TI  - Quantification of Helicobacter pylori infection: Simple and rapid 13C-urea breath
      test in Taiwan.
AB  - The 13C-urea breath test (13C-UBT) is a non-invasive method for detecting
      Helicobacter pylori. This study was performed to determine the cutoff value and
      evaluate the sensitivity and specificity of 13C-UBT in Taiwan. 13C-Urea (100 mg
      of 99% 13C-labeled urea) was dissolved in 50 ml sterile water for the test. The
      test meal for delaying gastric emptying was 100 ml fresh milk. Patients fasted
      for at least 6h. A baseline breath sample was collected 5 min after they had the
      test meal. Two other samples were collected at 15 and 30 min after the patients
      ingested the 13C-urea. The test was evaluated in 352 patients after routine upper
      gastrointestinal endoscopy, and the urease test, culture, and histopathology were
      taken as the gold standards for detecting H. pylori. According to the receiver
      operating characteristic (ROC) curves, we chose values of 2.8 and 4.2 excess
      delta 13CO2 per mil as the cut-off values for 15 and 30 min, respectively, post
      13C-urea. The sensitivity and specificity of 13C-UBT were 99% and 93% at 15 min,
      and 98% and 93% at 30 min post 13C-urea, respectively. The 13C-UBT breath test is
      an efficient non-invasive method of high sensitivity and high specificity for
      detecting H. pylori infection. We suggest that the use of fresh milk as the test
      meal and the detection of excess delta 13CO2 15 min after the ingestion of 13C
      urea are suitable for the clinical use of 13C-UBT. This test is simple and rapid.

PMID- 9658311
TI  - Endoscopic findings in transplanted allo-intestine of rats after discontinuance
      of immunosuppressive agent.
AB  - In clinical practice, graft rejection in small-bowel transplantation should be
      diagnosed before irreversible condition of the graft. We have already reported
      the usefulness of endoscopic examination for the early detection of acute
      rejection in a rat model. Here we evaluated rejection after discontinuance of
      methyl-deoxyspergualin by endoscopy. Heterotopic small-bowel transplantation was
      performed by the cuff method from a DA to a LEW rat. Endoscopic and histological
      examinations were performed through the stomas. Two-week administration of methyl
      deoxyspergualin significantly prolonged graft survival. Graft rejection after
      discontinuance of the agent occurred much more slowly than rejection without the
      immunosuppressive drug. Erosive mucosal changes were endoscopically observed in
      the early phase of rejection in rats that did not receive the immunosuppressant.
      However, endoscopic findings after discontinuance of methyl-deoxyspergualin
      indicated edematous changes and thickening of the wall without erosion, and,
      histologically, the grafted intestine showed slowly-progressing rejection with
      flattened villi. If we pay attention to edematous changes and hardening of
      intestinal wall, and take selective biopsies, endoscopic examination may improve
      the early diagnosis of slowly progressive rejection in the clinical setting.

PMID- 9658312
TI  - Telomere shortening in the colonic mucosa of patients with ulcerative colitis.
AB  - Telomere length in human somatic cells gradually decreases with the number of
      cell divisions and is regarded as a marker of somatic cell turnover. Mucosal
      cells of the affected colon show rapid turnover in individuals with active
      ulcerative colitis (UC). Telomere length was determined by Southern blot analysis
      of terminal restriction fragments (TRFs) from the colonic mucosa of 17 patients
      with UC in remission, two of whom showed dysplasia, and 17 control subjects
      without colitis. For each individual, mean TRF length was compared between rectal
      mucosa and unaffected cecal mucosa. The mean TRF length of the rectal mucosa was
      significantly less than that of cecal mucosa in UC patients (7.87 +/- 0.36kb
      versus 8.77 +/- 0.21 kb; P = 0.0015, Wilcoxon signed rank test), whereas no
      significant difference was detected in the control subjects. The extent of
      telomere shortening was 10.6 +/- 3.35% in UC patients, compared with 0.8 +/-
      0.64% in noncolitis controls (P = 0.0024, Mann-Whitney U-test). Four UC patients,
      two of whom had dysplasia, showed telomere shortening of more than 20% in the
      rectal mucosa. These observations suggest that telomere shortening in the colonic
      mucosa of individuals with UC may represent the history of mucosal inflammation
      during disease of long duration, and that it may contribute to aneuploidy in UC.

PMID- 9658313
TI  - Clinical significance of serum levels of CD44 variant exons 8-10 protein in
      colorectal cancer.
AB  - We examined serum levels of a CD44 splice variant that contained variant exons 8
      10 (CD44v8-10) as a tumor marker in colorectal cancer patients. We performed
      enzyme-linked immunosorbent assays in 81 sera obtained from 71 colorectal cancer
      patients and 10 healthy controls. Serum CD44v8-10 levels were significantly
      higher in the colorectal cancer patients than in the healthy controls (0.209 +/-
      0.098 versus 0.114 +/- 0.019 OD; P < 0.01). There was a close correlation between
      immunohistochemical expression and serum CD44v8-10 levels. Surgical resection of
      the tumors resulted in a reduction of serum CD44v8-10 levels. There was no
      significant correlation between serum CD44v8-10 level and serosal invasion or
      histologic type. However, a significant correlation was observed between serum
      CD44v8-10 level and lymphatic or venous invasion. In addition, serum CD44v8-10
      levels were significantly higher in carcinomas associated with lymph node or
      liver metastasis than in those without metastasis. These findings suggest the
      usefulness of serum CD44v8-10 level in the prediction of colorectal cancer
      metastasis.

PMID- 9658314
TI  - Detection of circulating anti-MUC1 mucin core protein antibodies in patients with
      colorectal cancer.
AB  - MUC1 mucin has a unique immunogenic peptide epitope in the extracellular domain,
      which has been shown to induce humoral and cellular immune response. In this
      study, we evaluated the pathophysiological significance of circulating anti-MUC1
      mucin core protein IgG antibodies (anti-MUC1 antibodies) in colorectal cancer by
      Western blot analysis and 51Cr release assay. Anti-MUC1 antibodies were detected
      in 5 of 31 (16.1%) healthy subjects and in 27 of 56 (48.2%) patients with
      colorectal cancer. The presence of circulating anti-MUC1 antibodies was not
      significantly correlated with the level of circulating antigen MUSE11 or with
      other clinicopathological parameters tested. The incidence of positivity for anti
      MUC1 antibodies in stage I and II (staged according to the General Rules for
      Clinical and Pathological Studies on Cancer of the Colon and Rectum of the
      Japanese Research Society for Cancer of the Colon and Rectum) cancers was 45.5%
      and 58.8%, respectively, suggesting that positivity for these antibodies may be
      of use as an adjunct for the diagnosis of colorectal cancer in the early stages
      in the absence of serious complications such as liver diseases. Because of the
      epitope similarity, anti-MUC1 antibodies in the serum may function in a manner
      similar to that of anti-MUC1 peptide monoclonal antibodies (mAbs). We therefore
      observed antibody-dependent cell mediated cytotoxicity with anti-MUC1 peptide mAb
      using MUC1 cDNA-transfected colon cancer CHC-Y1 cells as the target. The
      decreased sensitivity of MUC1 transfectants to effector cells was restored to a
      level equivalent to that in control cells. These data suggest that the detection
      of circulating anti-MUC1 antibodies may be a useful adjunct for the early
      diagnosis and immunological analysis of colorectal cancer.

PMID- 9658315
TI  - Altered hepatic hemodynamics and improved liver function following intrahepatic
      vascular infusion of prostaglandin E1.
AB  - Prostaglandin E1 (PGE1) has cytoprotective effects in the liver. To find how PGE1
      influenced hepatic hemodynamics, oxygen metabolism, and hepatic function, we
      carried out an experimental and a clinical study. PGE1 was continuously
      administered into the hepatic artery (n = 5) or portal vein (n = 5) at a rate of
      0.01 micrograms/kg per min in healthy mongrel dogs. In the clinical study, in
      eight patients PGE1 was administered through the hepatic artery at a rate of 0.01
      micrograms/kg per min after hepatic lobectomy. In the experimental study, hepatic
      hemodynamics and oxygen metabolism did not change during the administration of
      PGE1 into the portal vein. During administration of PGE1 into the hepatic artery,
      hepatic arterial flow increased 1.5-fold after administration compared to the
      rate before administration (P < 0.01). Hepatic arterial pressure, hepatic
      arterial resistance, and post-sinusoidal resistance significantly decreased after
      administration (P < 0.01, P < 0.01, and P < 0.05, respectively). Hepatic oxygen
      supply increased significantly (P < 0.01). In the patients, serum glutamic
      oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) levels
      remained low after surgery, and the recovery of protein synthesis was improved
      compared with that in eight hepatectomized patients without PGE1 administration
      (controls). The intrahepatic arterial infusion of PGE1 was considered useful for
      the recovery of liver function.

PMID- 9658316
TI  - Reduced expression and rare genomic alteration of nm23-H1 in human hepatocellular
      carcinoma and hepatoma cell lines.
AB  - We investigated the expression and genomic alteration of nm23-H1 (which encodes a
      nucleoside diphosphate, kinase A) in 12 human hepatocellular carcinomas (HCCs)
      and four hepatoma cell lines. The expression of nm23-H1 protein was significantly
      reduced in HCCs with intrahepatic metastasis (72%) compared with expression in
      HCCs without intrahepatic metastasis (38%). However, in two of three HCCs
      examined that had marked reduction of nm23-H1 protein, the nm23-H1 mRNA level was
      not reduced. A hepatoma cell line, HLF (phenotype, poorly differentiated
      carcinoma) revealed marked reduction of nm23-H1 protein compared with two other
      hepatoma cell lines, HuH-1 and HuH-2, although the mRNA level was similar in the
      three cell lines. No allelic deletion of the nm23-H1 gene was detected in the 12
      HCCs examined. No point mutation in the coding region of the nm23-H1 gene was
      observed in any of the 12 HCCs or the four hepatoma cell lines. These findings
      suggest that: (i) the expression of nm23-H1 protein is inversely associated with
      high metastatic potential of HCC, (ii) regulation of nm23-H1 expression may
      occasionally occur at both the transcriptional and post-transcriptional levels in
      HCC; and (iii) genomic alteration of nm23-H1 is a rare event in HCC.

PMID- 9658317
TI  - Circulating vascular endothelial growth factor (VEGF) is a possible tumor marker
      for metastasis in human hepatocellular carcinoma.
AB  - Vascular endothelial growth factor (VEGF) is closely related to angiogenesis in
      various human cancers. However, little is known of its circulating levels in
      hepatocellular carcinoma (HCC). We examined circulating VEGF levels in chronic
      liver disease to assess their clinical significance. Plasma VEGF concentrations
      were determined, by enzyme immunoassay, in patients with chronic hepatitis (CH; n
      = 36), liver cirrhosis (LC; n = 77), and HCC (n = 86) for a cross-sectional
      study. Plasma VEGF levels in healthy controls (n = 20) and CH, LC, and HCC
      patients were 17.7 +/- 5.4 (mean +/- SD), 30.6 +/- 22.8, 34.4 +/- 27.0, and 51.1
      +/- 71.9 pg/ml, respectively. The levels were significantly elevated in the HCC
      group, compared with the control, CH, and LC groups. Plasma VEGF levels in stage
      I, II, III, IVA, and IVB HCC patients were 27.6 +/- 16.1, 26.5 +/- 13.7, 35.8 +/-
      15.3, 45.4 +/- 39.4, and 103.1 +/- 123.2 pg/ml, respectively. The stage IVB
      patients with remote metastasis showed significantly marked elevation compared
      with the patients at the other stages. Platelet numbers were weakly correlated
      with plasma VEGF levels in the HCC group. Plasma VEGF level was highly elevated
      in patients with HCC, particularly those with metastatic disease. We consider
      that plasma VEGF is a possible tumor marker for metastasis of HCC. Circulating
      VEGF may be derived mainly from the large burden of tumor cells, and partly from
      platelets activated by the vascular invasion of HCC cells.

PMID- 9658318
TI  - TGF-beta isoforms in alcoholic liver disease.
AB  - The increased deposition of extracellular matrix proteins in the liver is a key
      factor in the morbidity and mortality of alcoholic liver disease (ALD). This
      increased fibrosis may be due to a superabundance of profibrogenic factors such
      as transforming growth factor-beta (TGF-beta). The original peptide is now called
      TGF-beta 1, and two other isoforms have been recognized in humans (TGF-beta 2 and
      TGF-beta 3). It was the aim of the present study to determine the expression of
      the TGF-beta isoforms in different stages of ALD. Thirty patients with ALD had
      percutaneous liver biopsies performed for diagnostic purposes. They were grouped
      by clinical findings and by liver histology into four groups: I, steatosis; II,
      fibrosis; III, hepatitis; and IV, cirrhosis. An unused portion of each biopsy
      sample was used to evaluate the gene expression of TGF-beta 1, TGF-beta 2, and
      TGF-beta 3 by reverse transcription polymerase chain reaction (RT-PCR). The
      expression of all isoforms from patients was significantly greater than their
      expression in controls. No significant correlation was determined between TGF
      beta isoform expression and liver function test results. When the different
      isoforms were grouped by histology, increased expression with more severe disease
      was found; however, differences existed among the isoforms. In ALD, all TGF-beta
      isoforms were increased and their expression was significantly greater in
      patients with more active and advanced disease. RT-PCR is an effective method for
      evaluating gene expression in clinical samples which often provide a limited
      amount of tissue.

PMID- 9658319
TI  - Detection of Ki-ras and p53 gene mutations in tissue and pancreatic juice from
      pancreatic adenocarcinomas.
AB  - Pancreatic carcinomas have a high incidence of Ki-ras mutations, and the genetic
      change is thought to occur at an early stage in the carcinogenesis. The aim of
      this study was to evaluate the usefulness of detecting genetic mutations in pure
      pancreatic juice (PPJ). DNA was extracted from tissue specimens of pancreatic
      carcinomas and from cells in PPJ, and subjected to polymerase chain reaction
      single-strand conformation polymorphism analysis. Two types of mobility shifts
      that indicate Ki-ras mutations were observed in 13 of the 20 (65%) tissue
      specimens obtained by operation or autopsy. Ten of 15 specimens (67%) of PPJ
      collected from patients with pancreatic carcinomas showed two types of mobility
      shifts. Conventional imaging techniques did not show two in 10 of these patients.
      PPJ from patients with non-cancerous pancreatic diseases showed no Ki-ras
      mutations. The p53 tumor suppressor gene, examined by PCR-SSCP analysis, was
      mutated in 8 of the 20 tissue specimens obtained by operation or autopsy (40%).
      The detection of Ki-ras and p53 mutations in PPJ could be useful for the early
      diagnosis of pancreatic carcinomas, especially for neoplastic lesions of the
      intraductal type.

PMID- 9658320
TI  - Primary cancer of the small intestine and mutational analysis of the K-ras and
      p53 genes.
AB  - A 69-year-old woman was admitted to Hokuso Shiroi Hospital because of recurrent
      pain in the lower right side of the abdomen. Small-intestinal cancer was strongly
      suspected after fluoroscopy of the small intestine. Laparotomy showed advanced
      cancer of the ileum, of complete annular constrictive type, 9.5 x 5cm in size.
      Histologically it was moderately differentiated tubular adenocarcinoma. Neither
      visceral nor nodal metastases were found, and the patient has been well for the
      20 months since surgery. The strong resemblance between the epidemiological
      characteristics of small-intestinal cancers and colorectal cancers prompted us to
      investigate the carcinogenetic mechanisms at the molecular level. A point
      mutation at codon 12 of the K-ras gene was found, while no alterations were noted
      in the p53 gene, whose mutations are frequent in colon cancers. The
      carcinogenetic mechanisms of the small-intestinal cancer we experienced may thus
      differ from those of colon cancers.

PMID- 9658321
TI  - Anorectal leiomyosarcomas.
AB  - In adults, rectal leiomyosarcoma is uncommon, and anal leiomyosarcoma is even
      more rare. We report one patient with anal leiomyosarcoma and one patient with a
      biphasic clinical history, with three occurrences of perineal leiomyosarcomas
      after surgically resected rectal leiomyoma. We discuss the characteristics of
      these rare entities based upon a review of the literature.

PMID- 9658322
TI  - Pyoderma gangrenosum complicating ulcerative colitis: Successful treatment with
      methylprednisolone pulse therapy and cyclosporine.
AB  - A 32-year-old woman with ulcerative colitis had a relapsed of pyoderma
      gangrenosum during puerperium. Both the pyoderma gangrenosum and ulcerative
      colitis had been well controlled with oral prednisolone, but ulcerative colitis
      relapsed in pregnancy, and pyoderma gangrenosum relapsed in the puerperium. The
      pyoderma gangrenosum responded to methylprednisolone pulse therapy initially, but
      relapsed when prednisolone was tapered. A second trial of pulse therapy combined
      with cyclosporine resulted in complete remission of the pyoderma gangrenosum, and
      no recurrence was recognized after prednisolone was tapered. This is a very rare
      case of successful treatment with methylprednisolone pulse therapy combined with
      cyclosporine for pyoderma gangrenosum complicating ulcerative colitis.

PMID- 9658323
TI  - Fulminant hepatitis complicated by small intestine infection and massive
      hemorrhage.
AB  - A 34-year-old man diagnosed with fulminant hepatitis, caused by hepatitis B
      virus, and acute renal failure was referred to our hospital. After admission to
      the intensive care unit, the liver and renal failure were ameliorated. Melena
      requiring transfusion occurred during the course of his illness. Endoscopic
      examination demonstrated pseudomembranes, erosions, ulcers, and hemorrhage in the
      duodenum, the upper jejunum, and the terminal ileum, suggesting widespread
      lesions throughout the small intestine. Pseudomonas putida, Xanthomonas
      maltophilia, and Candida glabrata were cultured from ileal fluid. Candida
      glabrata was also detected in sputum, feces, and on an intravenous catheter tip.
      The patient was treated with amphotericin B and miconazole. The melena was
      ameliorated, but inflammation of the small intestine persisted. Although we had
      difficulty in treating the enteritis, the patient survived, and 1 year later
      colonoscopic examination demonstrated no abnormalities. The small intestine is a
      difficult site to examine, but endoscopic examination of this site is important
      when massive hemorrhage develops.

PMID- 9658324
TI  - Two patients with acute hepatitis B with suspected sexual transmission of
      hepatitis G virus.
AB  - Two patients with acute hepatitis B with suggested sexual transmission of
      hepatitis G virus (HGV) are reported. A total of 18 patients with community
      acquired acute hepatitis B were analyzed in this study. Two of the 18 patients
      (patients 1 and 2) were positive for serum HGV RNA at the initial consultation.
      Both patients had had sexual contact with prostitutes several weeks before the
      onset of acute hepatitis, and hepatitis B virus (HBV) was suggested to be
      infected through the sexual contacts. These patients showed no other history of
      exposure to possible transmission routes for blood-borne hepatitis viruses.
      Patient 1 was diagnosed as with acute HGV infection because the antibody to HGV
      envelope-2 protein seroconverted to positive during the course of acute
      hepatitis. HGV RNA was negative in a serum sample collected from patient 2 before
      the onset of acute hepatitis, also suggesting acute HGV infection. These results
      indicate that in patients 1 and 2 HGV was infected along with HBV through sexual
      contact. The clinical manifestations of acute hepatitis in the two patients with
      HGV co-infection did not differ from those in the 16 patients with HBV infection
      alone.

PMID- 9658325
TI  - Use of balloon-occluded retrograde transvenous obliteration with ethanolamine
      oleate for the treatment of hepatic encephalopathy in a cirrhotic patient with a
      large spontaneous splenorenal shunt.
AB  - We describe a technique for the treatment of hepatic encephalopathy in a
      cirrhotic patient with a large spontaneous splenorenal shunt. This large shunt
      was successfully occluded without severe complications by retrograde transrenal
      venous obliteration with ethanolamine oleate after balloon occlusion. This
      procedure may be an effective method to occlude a large spontaneous splenorenal
      shunt for the treatment of hepatic encephalopathy.

PMID- 9658326
TI  - An autopsy case of granulocytic sarcoma of the porta hepatis causing obstructive
      jaundice.
AB  - We describe an extremely rare case of granulocytic sarcoma of the porta hepatis
      causing obstructive jaundice. The patient was an 84-year-old man admitted because
      of obstructive jaundice. Ultrasonography (US) and computed tomography (CT)
      scanning of the abdomen disclosed a mass about 2.5 cm in diameter near the neck
      of the gallbladder, and thickening of the gallbladder wall. Based on these
      findings, gallbladder carcinoma was suspected. After endoscopic retrograde
      biliary drainage (ERBD) was performed, the jaundice resolved. However, blast
      cells were detected in the peripheral blood 51 days after admission, and
      laboratory studies disclosed acute myelocytic leukemia (AML: French-American
      British [FAB] type M0). We treated him conservatively, with antibiotics and ERBD
      but he died of disseminated intravascular coagulation. Autopsy showed that the
      suspected gallbladder carcinoma was actually a granulocytic sarcoma arising in
      association with AML and causing obstructive jaundice. The largest tumor involved
      the porta hepatis. It should be kept in mind that granuloctyic sarcoma is a
      possible cause of obstructive jaundice, even in patients with no evidence of AML.

PMID- 9658327
TI  - Pancreaticoduodenal artery aneurysms associated with celiac axis stenosis due to
      compression by median arcuate ligament and celiac plexus.
AB  - Celiac axis stenosis is frequently associated with pancreaticoduodenal artery
      aneurysms. Although the cause of stenosis was not clear in most of the reported
      cases, compression of the median arcuate ligament of the diaphragm was found to
      be responsible for the stenosis in 7 of 42 reported cases of this type of
      aneurysm. We report a case of aneurysm caused by compression of the median
      arcuate ligament of the diaphragm and celiac plexus. An asymptomatic 43-year-old
      Japanese man was admitted with a low echoic lesion in the uncus of pancreas.
      Computed tomographic scan and angiogram revealed stenosis of the celiac axis and
      two aneurysms in the inferior posterior pancreaticoduodenal artery. The celiac
      plexus and median arcuate ligament were divided surgically and normal flow was
      reestablished in the celiac axis. One of the aneurysms was resected and the
      afferent artery of the other aneurysm was ligated. In the setting of
      pancreaticoduodenal artery aneurysm associated with celiac axis stenosis,
      management of stenosis should be considered in addition to local treatment of the
      aneurysm. In this context, division of median arcuate ligament and celiac plexus
      or aorto-celiac bypass may normalize the flows in the pancreaticoduodenal arcade
      and could be effective in preventing aneurysm reformation.

PMID- 9658328
TI  - Two synchronous solid and cystic tumors of the pancreas.
AB  - We report a 17-year-old woman who had two synchronous solid and cystic tumors of
      the pancreas (SCTP) detected by abdominal echography and computed tomography.
      There was a 6 x 5 cm mass in the pancreatic body and a 3 x 3 cm mass in the tail,
      with the two lesions being separate. No distal metastases were detected. The
      resected tumors consisted of solid and cystic components and both were well
      demarcated with fibrous capsules. The larger tumor was predominantly solid and
      the smaller one was mostly hemorrhagic. On microscopy, the tumor cells were
      small, eosinophilic, and arranged, in part, like pseudorosettes. The tumor cells
      were immunohistochemically positive for alpha-1 antitrypsin, neuron-specific
      enolase, and synaptophysin. The final diagnosis was SCTP arising synchronously
      and independently at two sites. As far as we know, only one case of multicentric
      SCTP has been reported previously. Local recurrence of SCTP suggests the
      possibility of multicentric occurrence, and we believe that reports of such cases
      may increase in the future with advances in echography and computed tomography.

PMID- 9658329
TI  - Pancreatic pseudocyst associated with eating disorder.
AB  - We describe a patient with an eating disorder and hyperamylasemia originating
      from the salivary glands, who developed pancreatitis with a huge pancreatic
      pseudocyst. A 40-year-old woman was referred for the treatment of an eating
      disorder that had persisted for 9 years. She was admitted with abdominal pain,
      diarrhea, and nausea. She had bilateral parotid enlargement with marked elevation
      of total serum amylase level (3288 IU/l; normal range, 60-220) and an isolated
      increase of salivary isoamylase activity. After her symptoms resolved, oral
      intake of food was commenced. She subsequently complained of abdominal pain; this
      was associated with a slight elevation of serum pancreatic isoamylase and lipase
      levels, and a huge pancreatic pseudocyst was detected. Percutaneous drainage of
      the pseudocyst was successful. Endoscopic retrograde cholangiopancreatography
      demonstrated irregularity of the pancreatic duct. Based on these findings, the
      final diagnosis was parotid enlargement and acute exacerbation of chronic
      pancreatitis associated with a pancreatic pseudocyst in a patient with an eating
      disorder.

PMID- 9658330
TI  - Intrahepatic cholangiocarcinoma with increased serum CYFRA 21-1 level.
AB  - CYFRA 21-1 is a fragment of cytokeratin 19 (CK 19). Four patients with large
      intrahepatic (or peripheral) cholangiocarcinoma (CC) and high serum levels of
      CYFRA 21-1 (normal, < or = 2 ng/ml) are reported. CYFRA 21-1 levels exceeded 9
      ng/ml in all 4 patients. Carcinoembryonic antigen (CEA), was high in 1 (CEA;
      normal range, < or = 5.0 ng/ml) and carbohydrate antigen 19-9 (CA 19-9) was high
      in 3 (CA19-9; normal range, < or = 36 U/ml). We also measured serum levels of
      CYFRA 21-1 in 13 patients with hepatocellular carcinoma (HCC) more than 5 cm in
      diameter. Levels of CYFRA 21-1 exceeded 2 ng/ml in 9 of the HCC patients and were
      higher than 9 ng/ml in 2 of the HCC patients. Levels of alpha fetoprotein (AFP)
      and/or protein induced by vitamin K absence or antagonist II (PIVKA II) were
      elevated in all HCC patients (AFP, PIVKA II, respectively; normal range, < or =
      10.0 ng/ml and < or = 0.1 AU/ml) CYFRA 21-1 levels were measured twice or three
      times during the clinical course in 2 CC patients and in 6 HCC patients, and
      increased gradually with tumor growth in the 2 CC patients and in 3 of the 6 HCC
      patients. Marked increases in serum CYFRA 21-1 levels in patients with large
      liver cancers, particularly in those with normal levels of AFP and PIVKA II,
      would suggest the existence of intrahepatic CC rather than HCC.

PMID- 9658331
TI  - Multiple early bile duct carcinoma associated with congenital choledochal cyst.
AB  - Emergency ultrasonography showed a protruding tumor in the markedly dilated
      common bile duct of a 33-year-old Japanese woman. Magnetic resonance
      cholangiopancreatography also demonstrated the tumor clearly, almost as clearly
      as did percutaneous transhepatic cholangiography. With a diagnosis of common bile
      duct carcinoma associated with congenital choledochal cyst,
      pancreaticoduodenectomy was performed. In the resected specimen, as well as the
      protruding tumor, there was also a small slightly elevated lesion. Pathology
      examination showed adenocarcinoma limited to the fibromuscular layer in the
      protruding tumor, and adenocarcinoma limited to the mucosa in the elevated
      lesion. Prophylactic total excision of the choledochal cyst before the occurrence
      of malignant change is strongly recommended in patients with congenital
      choledochal cyst. However, in those who are reluctant to undergo the operation,
      periodic follow-up with ultrasonography and magnetic resonance
      cholangiopancreatography would be ideal to achieve early detection of malignant
      change.

PMID- 9658332
TI  - Ulcerative colitis and Crohn's disease--susceptibility genes and clinical
      patterns.

PMID- 9658333
TI  - GB virus C/hepatitis G virus infection in autoimmune liver diseases.

PMID- 9658335
TI  - A neurite outgrowth-inhibitory proteoglycan expressed during development is
      similar to that isolated from adult brain after isomorphic injury.
AB  - The expression of proteoglycans (PGs) in the mammalian central nervous system
      (CNS) appears to be strictly regulated both during development and after damage
      to the mammalian CNS. Recently, we have isolated from membranes of injured adult
      brain a neurite outgrowth-inhibitory proteoglycan (IMP), the activity of which
      could be specifically counteracted by a monoclonal antibody (mAB) against the PG.
      We described in this report the characterization of perinatal membrane
      proteoglycan (PMP), a heparan-sulfate/chondroitin-sulfate-containing PG expressed
      during brain development. Its maximal expression was observed around postnatal
      day 3, decreasing strongly in normal adult tissue. This PG was purified and
      characterized using mABs generated against IMP. The comparison of PMP and IMP
      properties indicates that the two PGs are highly related and share expression
      patterns, biochemical characteristics, and the ability to inhibit neurite
      initiation in culture. However, IMP and PMP displayed a distinct effect on
      neurite elongation, which may be explained by their differences in glycosilation
      pattern. The data presented in this report support the idea that proteoglycans
      expressed during CNS development are re-expressed following injury.

PMID- 9658334
TI  - Insulin-like growth factor-1 is a radial cell-associated neurotrophin that
      promotes neuronal recruitment from the adult songbird edpendyma/subependyma.
AB  - In the adult songbird forebrain, neurons continue to be produced from precursor
      cells in the forebrain ependymal/subependymal zone (SZ), from which they migrate
      upon radial guide fibers. The new neurons and their radial cell partners may
      coderive from a common SZ progenitor, which may be the radial cell itself. On
      this basis, we asked whether radial cells might provide trophic support for the
      migration or survival of newly generated neurons. We focused upon the insulin
      like growth factors (IGFs) IGF-1 and IGF-2, which have previously been shown to
      support the survival and differentiation of neural progenitor cells. We found
      that IGF-1 immunoreactivity was expressed heavily by adult zebra finch radial
      cells and their fibers, with little expression otherwise. IGF-2, in contrast, was
      expressed by parenchymal astrocytes and exhibited little radial cell expression.
      Despite their distinct distributions, IGF-1 and IGF-2 exerted similar trophic
      effects on finch SZ cells in vitro; both greatly increased the number of neurons
      migrating from explants of the adult finch SZ, relative to explants raised in low
      insulin, IGF-1-deficient media. However, neither factor extended neuronal
      survival. These results suggest that in neurogenic regions of the adult avian
      forebrain, IGF-1 acts as a radial cell-associated neuronal differentiation and/or
      departure factor, which may serve to regulate neuronal recruitment into the adult
      brain.

PMID- 9658336
TI  - Regulation of aromatase, 5 alpha- and 5 beta-reductase in primary cell cultures
      of developing zebra finch telencephalon.
AB  - Sex steroids act on the developing and adult telencephalon of songbirds to
      organize and activate the neural circuits required for the learning and
      production of song. Presumably, the availability of active androgens and
      estrogens to steroid-sensitive neural circuits controlling song is modulated by
      the local expression of androgen-metabolizing enzymes. Two enzymes, 5 alpha- and
      5 beta-reductase, are expressed widely in the songbird telencephalon, as they are
      in the telencephalons of other avian species. These enzymes convert circulating
      testosterone (T) into the active and inactive metabolites, 5 alpha- and 5 beta
      dihydrotestosterone (DHT), respectively. A third enzyme, aromatase, converts T
      into estradiol (E2) and is expressed at unusually high levels in several regions
      of the songbird telencephalon. In many tissues, including the brain, the
      regulation of expression of one or more of these enzymes can be a critical
      feature of their ability to control the production of active sex steroids. We
      have used primary cell cultures to examine factors that might regulate the
      expression of these enzymes in developing zebra finch telencephalon. Cultures
      were treated for 0-72 h with sex steroids (T, E2, 5 alpha-DHT, and 5 beta-DHT) or
      with dibutyryl cAMP. Afterward, activities of aromatase, 5 alpha- and 5 beta
      reductase were determined or total RNA was extracted for Northern analysis.
      Treatments with cAMP increased both aromatase activity and aromatase mRNA levels
      by 220%. E2 significantly reduced aromatase activity by an average 65%, whereas 5
      alpha- and 5 beta-DHT had no effect on aromatase activity. Compared to untreated
      controls, E2 treatment decreased aromatase mRNA levels by 56%. None of these
      treatments consistently affected either 5 alpha- and 5 beta-reductase activities.
      These results suggest that telencephalic E2 may regulate its own synthesis by
      repression of aromatase expression, whereas factors that upregulate cAMP in the
      telencephalon can increase the local concentrations of E2.

PMID- 9658337
TI  - Glomerulus development in the absence of a set of mitral-like neurons in the
      insect olfactory lobe.
AB  - Mitral cells are the first neurons in the mammalian olfactory bulb to synapse
      with olfactory receptor axons during glomerulus development, and in an
      invertebrate, the moth Manduca sexta, mitral-like neurons overlap very early with
      olfactory receptor axons as they begin to form protoglomeruli. The possibility
      for early interaction between receptor neurons and mitral-like neurons led us to
      ask whether such an interaction plays an essential role in glomerulus
      development. In the current study in the moth, we surgically removed a major
      class of these mitral-like neurons before glomeruli began to form and asked: (a)
      Is the formation of the array of olfactory glomeruli triggered by an interaction
      of the first-arriving receptor axons with the dendrites of mitral-like neurons?
      (b) At the level of individual glomeruli, must the mitral-like dendrites be in
      place either to maintain receptor axons in a glomerular arrangement, or to guide
      later-growing dendrites of other types into the developing glomeruli? Our results
      indicate that even without the participation of this group of mitral-like
      neurons, the array of sexually isomorphic ordinary glomeruli forms and the basic
      substructure of individual glomeruli develops apparently normally. We conclude
      that the mitral-like neurons in Manduca are not essential for the formation of
      ordinary olfactory glomeruli during development.

PMID- 9658338
TI  - p59fyn and pp60c-src modulate axonal guidance in the developing mouse olfactory
      pathway.
AB  - The Src-family tyrosine kinases p59fyn and pp60c-src are localized on axons of
      the mouse olfactory nerve during the initial stages of axonal growth, but their
      functional roles remain to be defined. To study the role of these kinases, we
      analyzed the trajectory of the olfactory nerve in E11.5 homozygous null mutant
      mice lacking single src or fyn gens and double mutants lacking both genes.
      Primary olfactory axons of single and double mutants exited the olfactory
      epithelium and projected toward the telencephalon, but displayed differences in
      fasciculation. The fyn-minus olfactory nerve had significantly more fascicles
      than than src-minus nerve. Most strikingly, the primary olfactory nerve of
      src/fyn double mutants showed the greatest degree of defasciculation. These
      defects, identified by NCAM labeling, were not due to apparent changes in the
      size of the olfactory epithelium. With the exception of the src-minus mice, which
      had fever fascicles than the wild type, no obvious differences were observed in
      coalescence of vomeronasal axons from mutant mice. The mesenchyme of the double
      and single mutants exhibited only subtle changes in laminin and fibronectin
      staining, indicating that the adhesive environment of the mesenchyme may
      contribute in part to defects in fasciculation. The results suggest that
      signaling pathways mediated by p59fyn and pp60c-src contribute to the appropriate
      fasciculation of axons in the nascent olfactory system, and comprise partially
      compensatory mechanisms for axonal adhesion and guidance.

PMID- 9658339
TI  - Thrombin is an extracellular signal that activates intracellular death protease
      pathways inducing apoptosis in model motor neurons.
AB  - Apoptosis, often also termed "programmed cell death", occurs in normal
      development in the brain and spinal cord. Important to concepts of disease and
      potential intervention is the exciting finding that apoptosis is also found after
      neurotrauma and in a number of neurodegenerative diseases. Although the precise
      mechanism of neuronal cell loss remains unknown, much emphasis has been placed
      recently on the activation of cell death protease cascades within the cell. How
      these cascades may be activated, especially from extracellular influences, is
      currently poorly understood. Thrombin, the multifunctional coagulation protease,
      is an early phase modulator at sites of tissue injury and has been shown to
      induce cell death in neurons by an apoptotic mechanism by activating its
      receptor, PAR-1. Using a model motor neuronal cell line, NSC19, which we have
      shown undergoes apoptosis after treatment with classic apoptosis inducers such as
      the topoisomerase inhibitors camptothecin and etoposide, we unambiguously found
      that nanomolar thrombin induced characteristic signs of apoptosis. Strikingly,
      endonucleolysis was accompanied by an increase in caspase-3-like activity in
      cellular extracts, which correlated with both detection of caspase-induced
      signature cleavage of the cortical cytoskeleton component nonerythroid spectrin
      (alpha-fodrin) and identification of increased accessibility of a caspase
      cleavage domain, using an antibody (Ab127) made against a synthetic peptide
      KGDEVD. Demonstrating that thrombin activation of death proteases was linked to
      cell death, we were able to inhibit thrombin-induced apoptosis by using a caspase
      family inhibitor, benzyloxycarbonyl-Asp-(oMe)-fluoromethyl ketone (Boc-D-FMK).
      These novel results demonstrate that thrombin serves as an extracellular "death
      signal" to activate intracellular protease pathways. These pathways lead to
      apoptotic cell death and can be modulated by inhibiting caspase activity
      downstream to PAR-1.

PMID- 9658340
TI  - Conspecific and heterospecific song discrimination in male zebra finches with
      lesions in the anterior forebrain pathway.
AB  - Adult zebra finches can produce normal song in the absence of Area X, IMAN, or
      DLM, nuclei that constitute the anterior forebrain pathway of songbirds. Here, we
      address whether lesions involving Area X and IMAN affect adult male zebra
      finches' ability to discriminate between conspecific or heterospecific songs.
      Intact birds and lesioned birds were trained on an operant GO/NOGO conditioning
      paradigm to discriminate between hetero- or conspecific songs. Both lesioned and
      intact birds were able to learn all discriminations. Lesioned and intact birds
      performed equivalently on canary song discriminations. In contrast,
      discriminations involving bird's own song took significantly more trails to learn
      for lesioned birds than for intact birds. Discrimination between conspecific
      songs in general also took longer in the lesioned birds, but missed significance
      level. Birds with control lesions medial to Area X did not show any differences
      from intact animals. Our results suggest that an intact anterior forebrain
      pathway is not required to discriminate between heterospecific songs. In
      contrast, Area X and IMAN contribute to a male zebra finch's ability to
      discriminate between its own song and that of other zebra finches.

PMID- 9658341
TI  - Dynamic behavior of the ends of growing parallel fibers in early postnatal rat
      cerebellum.
AB  - The molecular layer of the cerebellum contains parallel fibers, the axons of
      granule neurons. We have examined the morphology and behavior of parallel fiber
      growth cones in the early postnatal rat cerebellum using the fluorescent tracer
      DiI. Parallel fiber growth cones distributed into three categories based on size
      and shape: short torpedo-like, long torpedo-like, and lamellopodial in form. The
      torpedo-like growth cones were modified by the addition of lamellopodia and/or
      filopodia, and the lamellopodial growth cones were often decorated with a
      filopodium. These three different growth cone morphologies were found throughout
      the growing region of the molecular layer. The nascent axons elaborated by
      premigratory granule neurons differed form the longer axons of more developed
      neurons in that they often had forked growth cones and extensive lamellopodial
      decoration along the axon shaft. Growth cones in living slices closely resembled
      those observed in the fixed preparations. The living growth cones exhibited
      frequent lamellopodial rearrangement and a side-to-side headwaving movement. The
      axon proximal to the growth cone was also dynamic. The axons curved and
      undulated, and mobile swellings formed along the axon shaft. These observations
      show that the growth cones of parallel fibers are similar to growth cones
      described for axons in other developing systems in terms of size, morphological
      characteristics, and dynamic behavior.

PMID- 9658342
TI  - The effect of shoulder magnetic resonance imaging on clinical decision making.
AB  - One hundred cases were prospectively evaluated to determine the impact of
      magnetic resonance imaging on clinical decision making in an orthopaedic practice
      devoted to the treatment of disorders about the shoulder. Each was analyzed for
      changes in the clinical diagnosis or treatment. A change that either changed the
      primary diagnosis or type of treatment (operative versus nonoperative) was
      classified as category one. If additional clinically relevant findings were noted
      on the imaging studies without altering the primary diagnosis, or if the form of
      treatment was modified but not changed from operative or nonoperative, it was
      considered category two. Among the 100 imaging studies reviewed, category one and
      two changes were observed in 11 and 7 cases, respectively. Magnetic resonance
      imaging was particularly helpful in diagnosing ganglion cysts about the shoulder,
      a category one change in three out of three cases. For specific diagnoses a
      category one or two change was observed in 17% (10 of 59), 29% (4 of 14), 8% (1
      of 13),and 100% (2 of 2) for rotator cuff disease, glenohumeral instability,
      adhesive capsulitis, and biceps disease, respectively. In 35 cases magnetic
      resonance imaging was considered to be unnecessary for the diagnosis or treatment
      of the patient. For the 65 patients who underwent magnetic resonance imaging,
      category one and two changes were noted in 10 and 5 patients, respectively.
      Statistical significance was demonstrated for category one changes in the entire
      group (100 cases) and the in subgroup recommended for magnetic resonance imaging
      (65 cases) (p < 0.05), indicating that the judicious use of magnetic resonance
      imaging can have a significant increase its impact on clinical decision making.
      Magnetic resonance imaging was found to be of limited diagnostic value in
      patients with an isolated primary clinical diagnosis of adhesive capsulitis,
      glenohumeral or acromioclavicular arthritis, brachial plexopathy, and cervical
      degenerative disk disease.

PMID- 9658343
TI  - A modification of Henry's anterior approach to the humerus.
AB  - A retrospective chart review identified patients who had surgery through Henry's
      standard anterior and anterolateral approaches to the humerus. Of the patients
      contacted, 62% had problems with the skin incision with reports of pain,
      numbness, and tingling around the scar. The frequency of cutaneous problems
      including neuroma prompted an anatomic study; the lower lateral cutaneous nerve
      branches to the arm were dissected in seven cadaver arms to determine their
      course. Henry's incision was then compared with a midline anterior incision. The
      cutaneous nerves were noticeably less numerous and smaller in diameter in the
      midline incision, probably related to the internervous, or watershed zone of
      cutaneous nerves in the anterior midline of the arm. Henry's standard
      intermuscular humeral exposure was no more difficult with the anterior midline
      incision. This study supports the notion that an anterior midline incision to
      approach the shaft of the humerus would minimize scar discomfort from cutaneous
      nerve injury.

PMID- 9658344
TI  - Change of calcifications after arthroscopic subacromial decompression.
AB  - Fifty patients were reviewed after arthroscopic subacromial decompression. Twenty
      five had calcific deposits in the rotator cuff visible on x-ray evaluation. Each
      patient with calcification was matched with a patient without calcification who
      had a similar state of the rotator cuff, date of surgery, age, and sex. The
      calcific deposits were left untouched in all cases. No significant difference was
      found in the postoperative outcome between the patients in the two groups
      measured by the Constant score. Before surgery 7 (28%) patients had
      calcifications of < 5 mm, and 18 (72%) patients had calcifications that were > or
      = 5 mm. At a 2-year follow-up (n = 24) these figures were 20 (83%) and 4 (17%),
      respectively (p < 0.001). Postoperative x-ray evaluations revealed a
      disappearance or decrease in size of the calcific deposits in 19 (79%) of the
      patients. These results provide new information on the course of calcifying
      tendinitis, which may indicate that we can leave calcific deposits untouched
      within the rotator cuff when performing arthroscopic subacromial decompression.

PMID- 9658345
TI  - Frozen shoulder: arthroscopy and manipulation under general anesthesia and early
      passive motion.
AB  - During a 15-month period, 24 patients with arthroscopically verified frozen
      shoulders were treated with manipulation while under general anesthesia and early
      passive motion. The minimum follow-up was 12 months, and the average duration
      from onset of the disease until treatment was 8 months. All patients had moderate
      to severe pain, and the average range of motion was less than 40% of the opposite
      shoulder. During the follow-up period, 75% of the patients obtained normal or
      almost full range of motion, and 79% had slight pain or no pain at all. Eighteen
      (75%) patients returned to work 9 weeks (mean) after treatment. There was no
      relationship between the end result and the initial pathologic condition. We
      believe that manipulation combined with arthroscopy is an effective way of
      shortening the course of an apparently self-limiting disease and should be
      considered when conservative treatment has failed.

PMID- 9658346
TI  - Magnetic resonance imaging of suprascapular nerve palsy.
AB  - In magnetic resonance imaging of peripheral nerve palsy, changes of signal
      intensity are often found in paralyzed muscles. The purpose of this report is to
      clarify the relation between magnetic resonance imaging findings and clinical
      examination in suprascapular nerve palsy. The subjects were 12 patients with
      suprascapular nerve palsy who underwent magnetic resonance imaging examinations.
      In 9 of 12 cases ganglion cysts were found at the spinoglenoid notches. On T1
      weighted images the signal intensity of infraspinatus muscle was high in four
      cases but normal in the supraspinatus muscle in all cases. On T2-weighted images
      the signal intensity of infraspinatus muscle was high in six cases, and that for
      supraspinatus muscle was high in one case. In two cases the high intensity of
      palsied muscles became normal after the palsy recovered. Magnetic resonance
      imaging is a useful examination of peripheral nerve palsy not only for the
      detection of ganglion cysts but also for assessing the stage of paralysis.

PMID- 9658347
TI  - Self-assessment of general health status in patients with five common shoulder
      conditions.
AB  - The SF-36 Health Survey is a patient self-administered general health status
      evaluation designed to measure the impact of disease on an individual's
      perception of his or her health. Five hundred forty-four patients with five
      common shoulder conditions (anterior glenohumeral instability (149 patients),
      complete reparable rotator cuff tear (111 patients), adhesive capsulitis (100
      patients), glenohumeral osteoarthritis (67 patients), and impingement (117
      patients)) completed the SF-36 Health Survey before undergoing treatment. When
      compared with U.S. general population norms, the patients with each of these
      shoulder conditions had statistically significant decreases in their health for
      Physical Functioning, Role-Physical, Bodily Pain, Social Functioning, Role
      Emotional, and the Physical Component Summary as measured by the SF-36 Health
      Survey. Comparison with published data demonstrated that these shoulder
      conditions rank in severity (in terms of affecting a patient's perception of his
      or her general health) with five major medical conditions (hypertension,
      congestive heart failure, acute myocardial infarction, diabetes mellitus, and
      clinical depression). The data presented in this study should serve as a baseline
      to document the impact of shoulder musculoskeletal conditions and possibly to
      allow comparison among various methods of operative and nonoperative treatment.

PMID- 9658348
TI  - The spinoglenoid ligament and its relationship to the suprascapular nerve.
AB  - Entrapment of the suprascapular nerve by the inferior transverse scapular
      ligament or spinoglenoid ligament (SGL) has been discussed frequently in the
      literature, but it has not been well documented anatomically. Therefore the
      mechanism of entrapment is not well understood. When isolated atrophy and
      denervation of the infraspinatus muscle have been noted, compression of the
      muscle's motor branch at the spinoglenoid notch has been implicated. This
      anatomic and morphologic study investigates the role of the SGL in entrapment
      neuropathy of the infraspinatus. We used 23 shoulders from 19 cadavers, 5 women
      (8 shoulders) and 14 men (15 shoulders), with a mean age of 67.9 (54 to 78)
      years. The presence or absence of the SGL was noted. The length, width, and
      orientation of the SGL; size and shape of the tunnel to the infraspinatus fossa;
      and distance of the notch to the posterior glenoid rim were determined. The SGL
      was present in 14 (60.8%) shoulders, 5 (36%) women and 9 (64%) men. The SGL was
      wider at the superior entrance of the tunnel and fanned and twisted toward the
      inferior aspect. In all specimens the SGL fibers inserted into the posterior
      shoulder capsule. The mean length for the upper part of the SGL was 17.5 +/- 2.6
      mm in men and 15.8 +/- 1.8 mm in women, and the lower part was 14.1 +/- 2.4 mm
      and 12.9 +/- 1.8 mm, respectively. The widths of the SGL at the origin of the
      scapular spine were 12.2 +/- 3.9 mm for men and 10.4 +/- 2.7 mm for women,
      whereas the insertion site widths were 15.8 +/- 2.2 mm for men, and 16.1 +/- 3.8
      mm for women. The midportion width of the SGL was 6.8 +/- 1.9 mm in men and 5.8
      +/- 2.1 mm in women. During cross-body adduction and internal rotation of the
      glenohumeral joint, the interaction of the SGL and the posterior capsule resulted
      in a tightening of the SGL. The suprascapular nerve moved laterally and stretched
      underneath the SGL in this position.

PMID- 9658349
TI  - Rehabilitation after subcutaneous transposition of the ulnar nerve: immediate
      versus delayed mobilization.
AB  - We studied 36 patients who had clinical signs and symptoms consistent with
      cubital tunnel syndrome and in whom nonoperative management failed. These
      patients underwent anterior subcutaneous transposition of the ulnar nerve
      followed by either immediate (20 patients) or delayed (16 patients) mobilization.
      All patients were evaluated with an outcomes assessment questionnaire, and 35 of
      the 36 were given repeat physical examinations. After surgery, there were no
      significant differences between the two groups in pain relief, weakness, or
      patient satisfaction (71% of the immediate mobilization group and 74% of the
      delayed group) were satisfied. Secondary quantitative outcomes such as grip
      strength, lateral pinch, or two-point discrimination were also not significantly
      different between the groups. Both groups had a statistically significant
      improvement in first dorsal interosseous and adductor pollicis muscle strength.
      In the immediate mobilization group, however, patients returned to work and
      resumed activities of daily living earlier (median 1 month) than patients in the
      delayed mobilization group (median 2.75 months). Therefore, we conclude that
      anterior subcutaneous transposition provides a high degree of satisfaction and
      relief of symptoms regardless of when mobilization is initiated. However,
      immediately mobilizing the patient significantly influenced how early the patient
      returned to work and resumed activities of daily living.

PMID- 9658350
TI  - Musculocutaneous nerve entrapment revisited.
AB  - Compression of the lateral cutaneous nerve of the forearm (LCNF), the distal
      sensory termination of the musculocutaneous nerve, can occur below the biceps
      aponeurosis, most commonly after strenuous elbow extension or forearm pronation.
      Between 1965 and 1992, 15 patients reported pain in the anterolateral elbow with
      "burning" into the forearm. There was a minimum 2-year follow-up of all patients
      in the study (average 13.4 years, median 15 years). All patients were managed
      conservatively for 12 weeks. Of the 15 patients, 11 required operative
      decompression that involved resecting a triangular wedge of aponeurosis overlying
      the nerve. Of the four nonoperative patients, one had persistent hypesthesia even
      though pain was relieved and range of motion was restored. Of the 11 patients
      treated operatively, none had recurrence of hypesthesia, and all patients
      continued to have complete relief of pain and full range of motion. One
      additional patient required surgery for lateral epicondylitis 2 years later.
      There were no operative complications.

PMID- 9658351
TI  - Electromyographic analysis of shoulder function during the volleyball serve and
      spike.
AB  - The purpose of this study was to describe the electromyographic (EMG) pattern and
      relative intensities of 8 shoulder muscles during the volleyball serve and spike
      in 15 professional or collegiate-level athletes. The EMG analysis was
      synchronized with high-speed cinematography to discern phases of the spike and
      serve. During the spike, the anterior deltoid and supraspinatus functioned
      together to elevate and place the humerus throughout all phases. During cocking
      the infraspinatus and teres minor acted together to rotate the humerus
      externally. In acceleration, however, these muscles behaved independently;
      activity of the teres minor remained high, whereas the activity of the
      infraspinatus declined. The anterior wall muscles functioned to decelerate the
      humerus during cocking and acted as internal rotators during acceleration. Muscle
      activities recorded for the serve followed similar patterns as those seen for the
      spike, but with lower amplitudes. These data illustrate the complex sequence of
      shoulder muscle activity necessary to play competitive volleyball.

PMID- 9658352
TI  - Shoulder ultrasound: diagnostic accuracy for impingement syndrome, rotator cuff
      tear, and biceps tendon pathology.
AB  - We sought to determine the accuracy of ultrasound for the preoperative evaluation
      of shoulder impingement syndrome, rotator cuff tear, and abnormalities of the
      long head of the biceps tendon. The findings in 42 consecutive surgical cases
      were compared with the preoperative sonographic readings. Ultrasound detected all
      of the 10 full-thickness cuff tears identified at surgery (sensitivity 1.0,
      specificity 0.97) but detected only 6 of 13 partial-thickness cuff tears
      (sensitivity 0.46, specificity 0.97). A full-thickness tear was falsely diagnosed
      in one case of severe cuff abrasion. Dynamic scan criteria correctly diagnosed
      impingement in 27 of 34 cases (sensitivity 0.79, positive predictive value 0.96).
      Abnormalities of the long head of the biceps were accurately diagnosed with the
      exception of low-grade tendinitis and the superior labral tear, anterior to
      posterior, lesion. We concluded that ultrasound is a sensitive and accurate
      method of identifying patients with full-thickness tears of the rotator cuff,
      extracapsular biceps tendon pathology, or both. Dynamic ultrasound can help
      confirm, but not exclude, a clinical diagnosis of impingement.

PMID- 9658353
TI  - Hyperextension of the elbow joint: pathoanatomy and kinematics of ligament
      injuries.
AB  - According to an epidemiologic study (Scand J Med Sci 1996/ 6: 297-302) the
      mechanism of "handball goalie's elbow" may be forced hyperextension. The
      pathomechanics of hyperextension were studied in nine macroscopically normal male
      cadaver elbow joints. The mean age of the donors was 43.2 years (range 25 to 61
      years). Kinematic tests were performed with an experimental three-dimensional
      kinematic loading apparatus. Hyperextension loads induced joint laxity during
      flexion of less than 50 degrees. The kinematic changes were significant in joint
      flexion during forced valgus and external and internal axial rotation, but were
      not significant in flexion during forced varus. No instability was found with
      flexion beyond 90 degrees. The hyperextension loads produced four lesions: (1)
      anterior capsule rupture; (2) L-shaped rupture of the pronator/flexor origin with
      elongation of the anterior part of the medial collateral ligament; (3) occasional
      incomplete rupture of the lateral collateral ligament; and (4) small fragments of
      cartilage near the posterior edge of the ulna in one of the specimens. One or
      more of these lesions may be responsible for the symptoms in "handball goalie's
      elbow."

PMID- 9658354
TI  - Anthropometry of the scapula: clinical and surgical considerations.
AB  - Anthropometric measurements were taken on 266 scapulas from the "G. Marro"
      Egyptian skeletal collection of the Department of Anthropology of the University
      of Turin in Italy to study the orthopaedic pathologic condition of the shoulder
      joints. Data were taken on the size and shape of the acromial arch in relation to
      the inclination and anatomic variants of the acromion. The rarity of the "hooked"
      form was confirmed, and two variants of the acromial vault (i.e., one
      predominantly osseous and the other predominantly fibrous) were recognized. The
      spatial location and biomechanical importance of the coracoid process were
      considered. Orientation of the glenoid fossa furnishes an osseous base for the
      stability of the scapulohumeral joint both anteroposteriorly and vertically.
      Observations on current practices of surgical intervention on the shoulder as
      reported in the literature and some anatomic skeletal basis of surgical access
      are discussed.

PMID- 9658355
TI  - Axillary artery injury as a complication of proximal humerus fractures.
AB  - Proximal humerus fractures are common injuries and represent approximately 5% of
      all fractures. These fractures are infrequently associated with neurovascular
      injuries. Brachial plexus injuries are uncommon, whereas axillary artery injuries
      are rare. A review of 19 previously reported cases of axillary artery injury
      after proximal humerus fracture revealed that 84% occurred in patients older than
      50 years, 53% were associated with brachial plexus injury, and 21% resulted in
      upper extremity amputation. This study describes a case of axillary artery injury
      after proximal humerus fracture and, on the basis of a literature review, offers
      suggestions for the early diagnosis and effective treatment of this uncommon
      injury.

PMID- 9658356
TI  - A rare variation of the biceps: a possible cause of degeneration of the rotator
      cuff.

PMID- 9658357
TI  - Deltoid contracture exhibiting anterosuperior subluxation of the shoulder joint.

PMID- 9658358
TI  - HIV/AIDS funding: we still need it.

PMID- 9658359
TI  - Hazardous terrain and over the edge: the survival of HIV-positive heterosexual,
      minority men.
AB  - The purpose of this study was to describe and explore the experience and
      perceptions of heterosexual minority men living with and surviving HIV infection.
      This descriptive, exploratory qualitative study used in-depth interviews that
      were guided by Rosenstock's health belief model and Ajzen's theory of planned
      behavior. A purposive sample of 18 HIV-positive heterosexual, minority men were
      accrued from an outpatient HIV/AIDS clinic in upstate New York and a community
      based AIDS service organization in New York City. The findings revealed that the
      experience of surviving HIV infection encompassed several stages. The men of this
      study described the choices they made in adolescence that led them down a trail
      of life that may be metaphorically described as "hazardous terrain," as the
      majority became involved in substance use or other illicit activities. With the
      diagnosis of HIV infection came a "Falling Off" stage, in which the participants
      went "over the edge" and initially were afraid to die but realized at this point
      that they were okay but vulnerable. The next stage was "Hanging On," in which
      they attempted to gain control, reevaluated priorities, and developed a new
      perspective on life and health. In the "Pulling Up" stage, participants realized
      that the rescue team included self, God, family, and friends, with self-rescue
      occurring on emotional, physical, and spiritual levels. As the participants
      reached the "Turning Around" stage, they began to accept responsibility for their
      health, focused on their abilities rather than their limitations, and reframed
      their perspectives to living with rather than dying from HIV infection. This
      study has implications for health-education programs, AIDS prevention, health
      assessment, and interventions for HIV-positive, heterosexual, minority men.

PMID- 9658360
TI  - Support groups for people living with HIV/AIDS: a review of literature.
AB  - For more than a decade, support groups have been proposed as a key intervention
      for people living with HIV and AIDS (PLWAs). Despite this fact, there are still
      only a few articles that evaluate and compare outcomes of support groups so as to
      provide a scientific base for their usefulness and effectiveness. The purpose of
      this article is to critically review selected published literature on support
      groups and to assess gaps in research. In general, the reviewed literature
      evaluated support groups as an effective intervention, which is evident for this
      widespread support. However, because diverse populations of PLWAs have specific
      needs, the group and intervention should be designed to meet those needs.
      Specific recommendations for further research about support groups for PLWAs are
      offered.

PMID- 9658361
TI  - Rosehedge: a home health agency and adult family home.

PMID- 9658362
TI  - Therapeutic touch with HIV-infected children: a pilot study.
AB  - In this pilot study, 20 HIV-infected children, 6 to 12 years of age, were
      randomly assigned into therapeutic touch (TT) and mimic TT groups. The
      effectiveness of TT in reducing anxiety was evaluated. The self-report measure,
      the A-State Anxiety subscale of the Spielberger State-Trait Anxiety Inventory For
      Children, was administered before and immediately after interventions. As
      predicted, the TT intervention resulted in lower overall mean anxiety scores,
      whereas the mimic TT did not. These findings provide preliminary support for the
      use of TT in reducing the state anxiety of children with HIV infection.

PMID- 9658363
TI  - Cortisol upregulates HIV p24 antigen production in cultured human monocyte
      derived macrophages.
AB  - HIV infection is associated with hypercortisolemia. Since glucocorticoids have
      been shown to stimulate the replication of several viruses, we examined the
      effects of cortisol on HIV replication in cultured monocyte-derived macrophages
      (MDM), a cell type that has been proposed to serve as a viral reservoir. Our data
      revealed that physiological concentrations of cortisol upregulate viral
      replication in MDM. Because the dose-response curve for cortisol on HIV
      replication in vivo is not known, the clinical relevance of these findings remain
      uncertain. Clinical studies are needed to characterize the effects of
      corticosteroid therapy on viral burden in vivo.

PMID- 9658364
TI  - The reliability and validity of the subjective peripheral neuropathy screen.
AB  - Painful sensory neuropathy (PSN) is the most common neurological disorder
      associated with HIV infection and affects up to 30% of HIV-positive individuals.
      PSN may develop as a consequence of HIV infection or from the toxic effect of the
      antiretrovirals. Although several tools have been developed to screen for PSN,
      their validity and reliability has yet to be established among HIV-positive
      patients. The Subjective Peripheral Neuropathy Screen (SPNS) is a brief self
      report tool that is currently being administered in the AIDS Clinical Trials
      Group. The objective of this study was to establish the psychometric properties
      of the SPNS screening tool for the correct identification of PSN in HIV-positive
      individuals. Specifically the goals were to determine the reliability, the
      validity, and the diagnostic efficiency of the SPNS in the detection of PSN. Data
      were abstracted on subjects enrolled in an ongoing natural history cohort. The
      SPNS was administered to a convenience sample of 39 HIV-positive individuals with
      PSN and 44 HIV-positive controls. Results showed the SPNS to be internally
      consistent (Cronbach's alpha = .86). SPNS score differences assessed by t-test
      were significantly different for individual symptoms of parasthesias, numbness,
      and pain of the lower extremities, and for severity measures (the Clinical
      Severity Grade, and the Average Severity Score) between the HIV-positive groups
      (p < .05). Using Spearman's rank, significant correlations were demonstrated
      between the neurological exam and the Clinical Severity Grade and the Average
      Severity Score, the neurological exam and vibratory quantitative sensory testing
      (QST) only, and the severity measures and vibratory QST only. Sensitivity and
      specificity analysis demonstrated that numbness of the lower extremities was the
      symptom with the highest efficiency for correctly classifying PSN. Thus, internal
      consistency, construct validity, and criterion related validity were confirmed
      with the SPNS for the correct classification of PSN in HIV-positive individuals.

PMID- 9658365
TI  - Managing fever in HIV disease.

PMID- 9658366
TI  - Are all type I human interferons equivalent?
AB  - The Type I interferons are a family of closely related cytokines that have
      antiviral and immunostimulatory properties. There has been prolonged debate
      regarding the different interferon-alpha subtypes: with some authorities suggest
      that the different interferons have essentially similar properties but others
      argue that there are significant differences between them. Recent work has shown
      that the various interferon-alpha subtypes can interact with the interferon
      receptor components in different ways and can activate a number of different
      signalling pathways. Recent studies on the immunomodulatory properties of the
      Type I interferons indicate that there are profound differences between the
      subtypes. The clinical significance of all these differences remains to be
      determined.

PMID- 9658367
TI  - Evolution of hepatitis G virus infection and antibody response to envelope
      protein in patients with transfusion-associated non-A, non-B hepatitis.
AB  - The clinical significance and course of acute hepatitis G virus (HGV) infection
      were studied by measuring HGV RNA and antibody to HGV envelope protein E2 (HGV-E2
      antibody). A total of 59 patients with transfusion-associated non-A, non-B
      hepatitis, who were followed-up for more than 1 year, were selected
      retrospectively. HGV RNA was measured by reverse transcriptase (RT) and nested
      polymerase chain reaction (PCR) was performed, using primer sets, in the 5'-non
      coding region of the HGV genome. HGV-E2 antibody was measured by enzyme-linked
      immunosorbent assay (ELISA) using recombinant E2 protein. Of the 59 patients, 51
      (86%) were infected with hepatitis C virus (HCV) and 12 (20%) were infected with
      HGV; 11 of the 12 with HGV infection were also infected with HCV. HGV viraemia
      was cleared during the follow-up period in seven of the 12 patients with HGV
      infection. All these seven patients seroconverted for HGV-E2 antibody just before
      or just after the clearance of HGV viraemia. In contrast, all five patients
      without clearance of HGV viraemia were negative for HGV-E2 antibody (P = 0.0013).
      Of seven patients with continuous HGV viraemia at 1 year from the onset of acute
      hepatitis, four with HCV RNA showed chronic elevation of alanine aminotransferase
      (ALT) but three without HCV RNA did not. The severity of acute hepatitis was
      similar between patients with both HGV and HCV infections and in those with HCV
      infection alone. The majority of patients with HGV infection cleared the virus
      during long-term follow-up. Appearance of HGV-E2 antibody was associated with the
      clearance of HGV viraemia. An abnormal ALT level was noted to depend on HCV
      infection but not on HGV infection in both the acute and chronic phases of
      transfusion-associated hepatitis.

PMID- 9658368
TI  - Detection of hepatitis G virus RNA in patients with acute non-A-E hepatitis.
AB  - We investigated the possible role of hepatitis G virus (HGV or GBV-C) in the
      aetiology of acute non-A-E hepatitis in Argentina by detecting viral RNA in sera
      by reverse transcriptase-polymerase chain reaction (RT-PCR) using primers
      specific for the putative NS3 helicase region of HGV. Sixty two patients with
      acute hepatitis were included in this study. The absence of hepatitis A-E was
      confirmed by serological testing, and all patients were negative for HCV RNA and
      autoimmune markers. All patients denied alcohol intake and the use of hepatotoxic
      drugs. Their mean age was 35.3 years and 37 were males. HGV RNA was present in
      19/62 (30.6%) of the patients with non-A-E acute hepatitis. Among HGV-positive
      patients, three had parenteral risk factors within 3 months of onset, one was a
      health care worker, one was sexually promiscuous, one had travelled to the Middle
      East and 13 (68.4%) had no history of parenteral exposure. Epidemiological,
      clinical and biochemical features between HGV-positive and negative patients did
      not achieve statistical significance. Hence, HGV appears to play a role in the
      pathogenesis of acute viral hepatitis; however, the etiology of a significant
      number of hepatitis cases remains unclear, suggesting the existence of an
      additional agent(s). The absence of parenteral exposure in most of the HGV RNA
      positive patients in this study shows that routes of community-acquired HGV
      infection are not yet completely understood.

PMID- 9658369
TI  - Hepatitis G infection: role in cryptogenic chronic liver disease and primary
      liver cell cancer in the UK. Trent Hepatitis C virus Study Group.
AB  - Hepatitis G virus (HGV) is a flavivirus that can cause acute hepatitis and
      persistent infection but its role in chronic liver disease or primary liver
      cancer is unproven. In this study we have examined the prevalence of HGV RNA in
      the serum of patients with hepatitis C virus (HCV) infection and in patients with
      cryptogenic chronic liver disease, including non-alcoholic steatohepatitis
      (NASH), and in patients with HCV-related hepatocellular carcinoma (HCC) and HCC
      arising in patients with cryptogenic liver disease. One-hundred and thirty
      patients who were positive for antibody to HCV (anti-HCV), 54 patients with
      cryptogenic chronic liver disease (including 17 patients with NASH) and 46
      patients with hepatitis C-related (n = 27) or cryptogenic liver disease-related
      HCC (n = 19) were studied. HGV RNA was detected using nested reverse
      transcriptase-polymerase chain reaction (RT-PCR) and was found in 16.1% of
      patients with HCV infection. HGV RNA was not detected in any patient with
      cryptogenic liver disease. In patients with HCC, 7/34 samples were positive for
      HGV RNA and six out of seven HGV-positive subjects also had HCV infection. Only
      one patient with HCC in cryptogenic liver disease was positive for HGV RNA.
      Hence, cryptogenic liver disease in the UK is not caused by HGV/GBVc infection.
      It seems unlikely that HGV plays a significant role in hepatocarcinogenesis.

PMID- 9658370
TI  - Predictive value of aminotransferase and hepatitis B virus DNA levels on response
      to interferon therapy for chronic hepatitis B.
AB  - In a previously reported randomized controlled trial of interferon-alpha (IFN
      alpha) for chronic hepatitis B, we found a significant difference in response
      between Chinese adults with elevated vs normal pretreatment aminotransferase
      (ALT) levels. The aim of this study was to determine the correlation between
      serum hepatitis B virus (HBV) DNA levels and response to IFN therapy. HBV DNA
      levels in residual stored sera from patients who participated in the above trial
      were quantified by a branched DNA (bDNA) assay. Nominal logistic regression was
      used to estimate the probability of response to IFN treatment as a function of
      pretreatment ALT and/or HBV DNA levels. We found a significant (P < 0.01)
      correlation between the HBV DNA levels at midtreatment and response to IFN
      therapy. Response was achieved in 53% of patients who had undetectable HBV DNA
      levels at midtreatment but in only 17% of those who remained HBV DNA positive (P
      < 0.01). In contrast, the probabilities of response for patients with baseline
      HBV DNA levels over the range 10 to 10000 million equivalents (MEq) ml-1 were
      almost identical. We also found a significant correlation between the
      pretreatment ALT levels and response to IFN therapy. The probabilities of
      response for patients with pretreatment ALT levels of 500 and 100 IU l-1 were
      higher than for patients with normal ALT levels by two and onefold, respectively.
      Our findings may help to improve the cost-effectiveness of IFN therapy for
      chronic hepatitis B by guiding the selection of patients for therapy and in
      optimizing the duration of treatment for the individual patient.

PMID- 9658371
TI  - Systemic manifestations and liver disease in patients with chronic hepatitis C
      and type II or III mixed cryoglobulinaemia.
AB  - The aim of this study was to evaluate the prevalence of cryoglobulins in patients
      with chronic hepatitis B and C virus infection and to investigate the association
      of type II and type III mixed cryoglobulinaemia with systemic manifestations and
      liver disease stage and outcome in hepatitis C virus (HCV)-positive patients. We
      analysed the prevalence of cryoglobulinaemia in a cohort of patients with chronic
      liver disease and compared the systemic manifestations and liver involvement in
      HCV-positive patients with type II or type III mixed cryoglobulinaemia. The
      prevalence of serum cryoglobulins was significantly higher in HCV-positive
      patients than in hepatitis B surface antigen (HBsAg)-positive patients (55.4 vs
      20.6%). In HCV-positive patients, stage of liver disease correlated with the
      prevalence of cryoglobulinaemia. Patients with type II cryoglobulins showed a
      significantly higher risk of cirrhosis and of extrahepatic manifestations while
      patients with type III cryoglobulins had a significantly higher prevalence of
      hepatocellular carcinoma. During follow-up the former had an odds ratio of 11.9
      of death from extrahepatic complications while the latter had an odds ratio of
      3.4 of dying from hepatic disease. Our study confirms the high frequency of mixed
      cryoglobulinaemia in patients with chronic hepatitis C virus infection. The
      presence and type of cryoglobulins seem to be associated with different clinical
      manifestations and outcome.

PMID- 9658372
TI  - Serum hyaluronic acid is a useful marker of liver fibrosis in chronic hepatitis C
      virus infection.
AB  - Patients with chronic hepatitis C virus (HCV) infection are often asymptomatic
      with few clinical signs of liver disease. Recognition of the presence of fibrosis
      or cirrhosis is difficult without liver biopsy, but with the availability of
      effective treatments, such as interferon, and the potential for progression to
      hepatoma in some cases, an accurate measure of the stage of disease is important.
      Serum hyaluronic acid (HA) has been identified as a potential marker of fibrosis
      or cirrhosis in other settings. In a prospective study in 130 chronic HCV
      carriers therefore, serum HA concentrations were compared with conventional liver
      function tests (including alanine aminotransferase (ALT), a-glutathione-S
      transferase (GST) and serum HCV RNA in order to determine which identified the
      stage of liver fibrosis as assessed by liver biopsy most accurately. The median
      HA concentrations according to the stage of fibrosis 0, 1 & 2, 3 and 4 & 5 were
      17 g l-1 (range 5-37), 17 g l-1 (5-80), 30 g l-1 (10-105) and 350 g l-1 (20-800)
      respectively. The median HA concentration in stage 4 & 5 was significantly
      greater than in stages 0, 1 & 2 or 3. Serum HA concentration rose with age, but
      even when adjusted for age the median HA at stage 4 & 5 was greater than all
      other groups (95% CI of difference between the medians exceeded 0). Thus, serum
      HA gave a sensitivity and specificity for stage 4 & 5 fibrosis of 85% and 88%
      respectively, exceeding those for ALT or GST. In contrast, serum ALT or GST
      levels were not correlated with the stage of fibrosis although ALT was
      significantly greater in the cirrhotic group when compared to the group with no
      fibrosis (stage 0). There was no correlation between serum HA and either the
      grade of inflammatory changes or serum HCV RNA. These results suggest that serum
      hyaluronic acid is a useful marker of liver fibrosis in patients with chronic HCV
      infection. It could therefore be used to monitor patients at risk of progressive
      fibrosis, in controlled clinical trials, as a measure of response to antifibrotic
      therapy and in those in whom liver biopsy is difficult or contraindicated.

PMID- 9658373
TI  - Ribavirin monotherapy in patients with chronic hepatitis C: a retrospective study
      of 95 patients.
AB  - Ribavirin is a purine nucleoside that inhibits the replication of a variety of
      RNA viruses and was shown to have a transient efficacy in chronic hepatitis C
      during short-term therapy. We have analysed retrospectively its efficacy in 95
      patients with liver biopsy-proven chronic hepatitis C. Patients received oral
      ribavirin (600-1200 mg daily) for a mean duration of 11 months. Alanine
      aminotransferase (ALT) levels returned to normal values in 38 patients (40%) and
      decreased by more than 50% in 20 other patients (21%). HCV RNA clearance from
      serum was observed in seven patients (8%). The biochemical response rate was
      higher in patients with chronic hepatitis (54%) than in those with cirrhosis
      (24%) (P = 0.003). Clearance of HCV RNA was observed in 10% of the patients with
      chronic hepatitis vs 4% of the patients with cirrhosis. In non-responders to
      interferon (IFN) therapy, ALT levels returned to normal values in 11 (26%) and
      HCV RNA became negative in one (2%), as compared to 48% and 3%, respectively, in
      those contraindicated for IFN. In 17 patients in whom paired liver biopsy
      specimens were available, the histology activity index (HAI) improved in 12.
      Therapy was generally well tolerated although 11 patients had to stop therapy
      because of side-effects, which were more common in cirrhotic patients. In
      conclusion, our results suggest that long-term administration of ribavirin is
      well tolerated and may be beneficial in controlling the progression of chronic
      hepatitis C. This may represent an alternative therapy in patients who have
      contraindications for interferon therapy or as a palliative approach in non
      responders to IFN.

PMID- 9658374
TI  - Role of immune serum globulins in pregnant women during an epidemic of hepatitis
      E.
AB  - The efficacy of an Indian preparation of immune serum globulins (ISG) was
      evaluated among pregnant women during an epidemic of hepatitis E in Karad,
      Western India from January to March 1993. Ten of 55 women receiving ISG developed
      immunoglobulin M (IgM) antibodies to hepatitis E virus (anti-HEV) during the 1
      month of follow-up compared with 18 out of 53 control subjects. Although the
      total number of recent HEV infections was significantly less in the ISG-treated
      group, no significant difference could be shown in the proportion of clinical
      hepatitis E cases because of the very small numbers of patients who developed
      clinical disease. The observed marginal beneficial effect of ISG might be the
      result of a low immunoglobulin G (IgG) anti-HEV IgG titre (1:500) of the ISG
      preparation used. Preparation and testing of high-titred ISG should be a high
      priority for protecting pregnant women during epidemics of hepatitis E.

PMID- 9658375
TI  - Production of antibody to hepatitis A virus and hepatitis B surface antigen
      measured after combined hepatitis A/hepatitis B vaccination in 242 adult
      volunteers.
AB  - Two batches of a new hepatitis A/hepatitis B combined vaccine were tested in 242
      healthy students. Three injections, given at 0, 1 and 6 months, produced
      seroconversion rates and hepatitis A virus (HAV) and hepatitis B surface antigen
      (HBsAg) antibody levels comparable to those reported after administration of
      separate monocomponent vaccines. The vaccine proved to be safe and well
      tolerated. Influence of host factors, such as elevated body mass index or gender,
      were investigated and proven to be of little influence on the immunoresponse.

PMID- 9658376
TI  - A novel in vitro model to screen steroid 5 alpha-reductase inhibitors against
      benign prostatic hyperplasia.
AB  - A convenient and rapid in vitro model to screen steroid 5 alpha-reductase
      inhibitors, which are effective in the treatment of benign prostatic hyperplasia
      (BPH), was developed. In the presence of nicotinamide adenine dinucleotide
      phosphate (NADPH), steroid 5 alpha-reductase converts testosterone to
      dihydrotestosterone (DHT) which is a major etiologic factor of BPH. NADPH has
      characteristic absorbance at 340 nm, and the absorbance spectrum may be used to
      identify NADPH as a kind of the substrate in this enzymatic reaction. In this
      paper, NADPH, steroid 5 alpha-reductase, series concentration of testosterone and
      finasteride, and 4 ml Tris-HCl buffer were continuously incubated together at 37
      degrees C and the NADPH OD values were continually measured. The descending rate
      of NADPH OD340nm value by linear regression from the beginning to the 10th minute
      is close to the initial velocity of the enzymatic reaction. The precise activity
      of the steroid 5 alpha-reductase was the slope after subtracting that of the
      blank control. The inhibition constant (Ki) of steroid 5 alpha-reductase
      inhibitors could be calculated according to the Lineweaver-Burk plots. Two drug
      screening models, the most common isotope model and the novel model, were
      compared in this paper. The result showed that the latter one is more economical,
      quicker and more effective than the former one.

PMID- 9658377
TI  - Transformation of bisphosphonates into insoluble material in human blood in
      vitro.
AB  - The aim of the study was to find out whether bisphosphonates transform into
      insoluble material in human blood and serum in vitro. Samples of fresh blood and
      serum were incubated with various concentrations of 14C-labelled clodronate,
      etidronate, pamidronate and tiludronate for 2 h and 8 h at 37 degrees C. The
      presence of unfiltrable material in the plasma separated from the blood, and in
      the serum were studied with 1) 100, 300 and 1,000 kd (kilo Daltons) filter tubes
      centrifuged at 3,000 g for 60 min, and 2) high-speed centrifugation at 13,000 g
      for 30 min. The radioactivities in the ultrafiltrates and supernatants were
      compared to those in the native plasma or serum. All bisphosphonates transformed
      into unfiltrable material, which was separated from the samples with the 100 and
      300 kd filters but not with the 1,000 kd filter. The material was not sedimented
      with the high-speed centrifugation. The lengthening of the incubation time from 2
      h to 8 h increased the unfiltrable fraction, which generally was dependent on the
      drug concentration in the blood, too. However, the fraction of the unfiltrable
      material did not seem to increase with time when the drug was incubated with
      serum instead of blood. Since drug binding to plasma proteins is generally a very
      rapid process, some factors other than proteins only, e.g. cations or cation
      residues, present in the blood but not in the serum, should be involved in
      transforming of bisphosphonates into insoluble material in the blood.

PMID- 9658378
TI  - Propofol concentrations in whole blood: influence of anticoagulants and storage
      time.
AB  - Blood samples for propofol determination are collected with oxalate, heparin and
      EDTA, but we have not found any study comparing the influence of those
      anticoagulants on propofol concentrations. This study was carried out on 50
      samples from patients taking propofol for anesthesia or cerebral protection.
      First, 26 samples were simultaneously collected into tubes containing lithium
      heparin or sodium fluoride potassium oxalate as anticoagulant. In a second
      investigation, 24 samples were simultaneously collected into tubes containing
      heparin or EDTA. Propofol was assayed by HPLC 2 days after sampling and 2 weeks
      later. In the first assay, propofol concentration in samples collected with
      heparin were similar to those collected with oxalate (3.65 +/- 3.50 vs. 3.62 +/-
      3.49 mg/l, ns) or EDTA (3.89 +/- 2.58 vs. 3.84 +/- 2.67 mg/L, ns). After storing
      for 2 weeks at 4 degrees C, propofol concentrations were slightly but
      insignificantly higher than in the first assay in samples collected with heparin
      (3.58 +/- 3.24 vs. 3.40 +/- 2.92 mg/l, ns), slightly higher in samples with
      oxalate (3.86 +/- 3.49 vs. 3.62 +/- 3.49 mg/l, p = 0.06), and slightly but
      significantly lower in samples with EDTA (3.63 +/- 2.67 vs. 3.84 +/- 2.67 mg/l, p
      < 0.05). It is concluded that the three anticoagulants used in this study seem to
      be suitable for determination of propofol concentration in whole blood, and that
      the stability of propofol concentration when samples are stored at 4 degrees C
      for up 2 weeks is acceptable.

PMID- 9658379
TI  - Effect of N-acetylcysteine on the oxidative burst induced by phagocytosis of
      bacteria in human leukocytes.
AB  - The basal peroxide production and the oxidative burst induced by phagocytosis of
      opsonized E. coli was studied by flow cytometry using dihydrorhodamine 123. The
      human leukocytes were incubated in the absence and presence of N-acetylcysteine.
      The oxidative response to the phagocytosis of bacteria differed among cell
      populations. Thus, 90% of granulocytes and 50% of monocytes showed an oxidative
      burst in response to opsonized bacteria while less than 1% of lymphocytes showed
      a fluorescence signal. N-Acetylcysteine (4.7, 9.5, 19, 38 or 76 mM) produced a
      dose-dependent inhibition of the oxidative response to phagocytosis in the three
      cellular populations reaching almost complete inhibition for 76 mM. This
      protective effect of N-acetylcysteine against oxidative stress in leukocytes was
      obtained without cytotoxicity (assessed by flow cytometry with staining with
      propidium iodide) or changes in the pH of the medium. These results give further
      support to the antioxidant effect of N-acetylcysteine in human peripheral blood
      cells.

PMID- 9658380
TI  - Cognitive involvement by negative modulation of histamine H2 receptors in passive
      avoidance task in mice.
AB  - In this study, the intracerebroventricular administration of 4-methylhistamine (3
      and 10 micrograms/head), a histamine H2 receptor agonist, shortened the step
      through latency in the retention trial using a step-through passive avoidance
      task in mice. This deteriorating effect of 4-methylhistamine (3 micrograms/head)
      was clearly antagonized by pretreatment with zolantidine (10 mg/kg, i.p.), a
      histamine H2 receptor antagonist, 20 min before an acquisition trial. Zolantidine
      alone at the dose tested had no effect. Thus, it is likely that activation of
      histamine H2 receptors has a deteriorating effect on avoidance learning in mice.
      The present results indicate the cognitive involvement by negative modulation of
      histamine H2 receptors in passive avoidance task in mice.

PMID- 9658381
TI  - Evidence of GABAergic modulation in melatonin-induced short-term memory deficits
      and food consumption.
AB  - Many of the pharmacological effects of melatonin have been found to be similar to
      those of benzodiazepines. In the present study, we analyzed the role of melatonin
      on short-term memory retrieval on transfer latency in elevated plus maze and food
      consumption behavior, and the effects were compared with those of diazepam.
      Melatonin dose-dependently (10-100 mg/kg) produced short-term memory deficit and
      it potentiated diazepam- (1 mg/kg) induced cognitive deficit in mice. Flumazenil
      (1 and 4 mg/kg) could reverse enhancement in diazepam-induced memory deficit by
      melatonin. Chronic treatment with melatonin (10 mg/kg/7d) produced a similar
      profile in transfer latency on elevated plus maze compared with that of diazepam.
      In a food consumption behavior study, melatonin (25 and 50 mg/kg) produced a
      significant hyperphagic effect compared to control. Flumazenil (4 mg/kg) could
      significantly reverse the hyperphagic effects induced by diazepam (2 mg/kg), but
      would be insignificant with regard to that due to melatonin. These findings
      provide further evidence that some of the pharmacological effects of melatonin
      are comparable with those of diazepam and may involve central GABAergic
      mechanism.

PMID- 9658382
TI  - Effects of gosha-jinki-gan, a kampo medicine, on peripheral tissue blood flow in
      streptozotocin-induced diabetic rats.
AB  - We examined the effects of Gosha-jinki-gan on peripheral tissue blood flow in
      streptozotocin-induced diabetic rats and its mechanism. The decrease in peroneal
      muscular blood flow in diabetic rats was dose-dependently improved by treatment
      with Gosha-jinki-gan (0.1-1 g/kg/day, p.o.) for 4 weeks. Investigation of the
      time course of blood flow in the hind paws revealed that single-dose of Gosha
      jinki-gan (0.3, 1.5 g/kg, i.d.) increased peripheral blood flow. Peripheral blood
      flow-increasing effects of Gosha-jinki-gan (1.5 g/kg, i.d.) were reduced in
      combination with atropine (1 mg/kg, i.v.), and disappeared by pretreatment with
      NG-nitro-L-arginine methyl ester (10 mg/kg, i.v.). Levels of aortic guanosine
      3',5'-cyclic monophosphate were dose-dependently increased by administration of
      Gosha-jinki-gan (0.3, 1.5 g/kg, p.o). These results suggest that Gosha-jinki-gan
      has vasodilating effects via increases in nitric oxide production. Gosha-jinki
      gan may be useful for treating peripheral circulation disorders in the diabetic
      state.

PMID- 9658383
TI  - The effect of antidepressants on rat aggressive behavior in the electric
      footshock and apomorphine-induced aggressiveness paradigms.
AB  - The effects of acute antidepressant treatment were studied in the electric
      footshock and apomorphine-induced aggressiveness paradigms and found to be
      ineffective in both experimental models. In the apomorphine-induced
      aggressiveness test, 100 mg/kg L-tryptophan challenge manifested the
      antiaggressive effect of 10 mg/kg fluoxetine (a selective serotonin reuptake
      inhibitor) treatment. Thus, concomitant L-tryptophan plus fluoxetine treatment
      decreased the intensity of aggressive postures and increased the time of latency
      before first attack. In conclusion, our study demonstrates the involvement of the
      serotoninergic neurotransmission in the neurobiology of aggressive behavior, but
      after acute treatment in normal rats, the antidepressants do not elicit
      antiaggressive effects.

PMID- 9658384
TI  - Antiischemic effect of ZK-118.182 in rabbits: a comparative study with iloprost.
AB  - The effects of ZK-118.182, a stable analogue of PGD2, were evaluated in an
      endothelin-1-induced cerebral ischemia rabbit model. Ischemia was induced by
      endothelin-1 injection (0.25 ng bolus) into subcavian artery and ischemic changes
      were assessed histologically by the number of ischemic neurons in the brain stem.
      ZK-118.182 (2 micrograms/kg, bolus into subclavian artery) reduced the number of
      ischemic neurons when injected 20 min after endothelin-1 injection, Iloprost, a
      stable analogue of PGI2, was also effective in reducing the number of ischemic
      neurons in a dose of 0.5 microgram/kg (bolus into subclavian artery). The results
      suggested that ZK-118.182 has a potent antiischemic effect which is comparable to
      that of iloprost in rabbits.

PMID- 9658385
TI  - Pharmacological activities of khellactones, compounds isolated from Peucedanum
      japonicum THUNB. and Peucedanum praeruptorium DUNN.
AB  - The spasmolytic and antiallergic effects of AA and BB, compounds isolated from
      Peucedanum japonicum THUNB. (P. japonicum THUNB.) and Peucedanum praeruptorium
      DUNN. (P. praeruptorium DUNN.), were investigated in isolated smooth muscle and
      rat PCA. AA and BB showed noncompetitive antagonistic effects on Ach- and
      histamine-induced contraction in the isolated guinea pig ileum. Both AA and BB at
      10(-6) g/ml caused a slight shift to the right of the dose-response curve for
      Ca2+ in isolated guinea pig ileum, and a concentration up to 3 x 10(-6) g/ml
      displayed noncompetitive antagonistic effects. The Ba2+ (3 x 10(-4) g/ml)-induced
      contraction in ileum and the histamine (10(-3) g/ml)-induced contraction in
      trachea were obtained to relaxation by AA and BB in a concentration-dependent
      fashion. AA and BB showed noncompetitive antagonist action on serotonin-induced
      contraction of the rat uterus excised 24-48 h after subcutaneous injection of
      female rats with estradiol. But, AA and BB were found to have hardly any
      inhibitory effect on rabbit thoracic aorta contractions induced by epinephrine (3
      x 10(-6) g/ml). When the effect of oral administration of 40 mg/kg dose of BB was
      tested on the rat homologous PCA using anti-egg albumin mouse serum dilutions
      (1:100, 1:250, 1:500 and 1:750), it inhibited the 1:750 serum reaction 42.6%, but
      the inhibition rates for the other dilutions were 12-20%. Thus, based on the
      results of testing AA and BB, compounds isolated from P. japonicum THUNB. and P.
      praeruptorium DUNN. were confirmed to possess a spasmolytic effect on different
      types of smooth muscle and a mild antiallergic effect. These findings are of
      interest in regard to the medical uses of P. japonicum THUNB. and P.
      praeruptorium DUNN. as a herbal drug for bronchial asthma, spasmolytic effect,
      etc.

PMID- 9658386
TI  - Prophylactic sodium valproate therapy in patients with drug-resistant migraine.
AB  - We assessed the efficacy of sodium valproate as a prophylactic agent in migraine
      headache. A prospective randomized study was conducted in adult patients who
      previously derived no significant benefit from most conventional prophylactic
      therapy for migraine. Twenty-seven patients with a diagnosis of migraine with
      aura or migraine without aura from a headache clinic received low dose sodium
      valproate for 3 months. Response to therapy was defined as 50% or greater
      reduction in the frequency of headache. Plasma drug level monitoring helped to
      identify four noncompliers who were excluded from the study. Seventeen (71%)
      patients observed improvement within 4-6 weeks of medication and remained well
      for 12 weeks. They were further followed up for 12-24 months. Two patients for
      side effects and 1 for nondrug-related problems were withdrawn from follow-up
      study. Twelve patients (60%) maintained their response for 12 months or longer.
      Clinical improvement (percentage reduction in the frequency of migraine attacks)
      correlated inversely with the plasma drug levels at 13-24 months and daily dose
      of valproate, among the responders, suggestive of a possible therapeutic window.
      In other words, patients who do not respond to low dose valproate are unlikely to
      benefit from further increase in dosage.

PMID- 9658387
TI  - Antigenic properties of recombinant glycosylated and nonglycosylated Pneumocystis
      carinii glycoprotein A polypeptides expressed in baculovirus-infected insect
      cells.
AB  - Since a continuous culture system is not yet available for the opportunistic
      fungal pathogen Pneumocystis carinii, obtaining suitable amounts of purified P.
      carinii antigens free of mammalian-host lung contaminants is difficult. Hence,
      production of recombinant antigen possessing epitopes found in native P. carinii
      antigens is critical for immunological studies. We utilized the baculovirus
      expression vector system (BEVS) in insect cells to determine whether B-cell
      epitopes present in the protein core of a native P. carinii surface glycoprotein
      were conserved in the recombinant polypeptide, and to investigate its
      glycosylation by insect cells. B-cell epitopes were retained, but the insect
      cells appeared to hyperglycosylate the recombinant protein.

PMID- 9658388
TI  - Overproduction of soluble, extracellular cytotoxin alpha-sarcin in Escherichia
      coli.
AB  - The goal of the present study was to establish the condition to obtain
      preparative amounts of the recombinant cytotoxin alpha-sarcin to be used for
      immunoconjugate production. alpha-Sarcin cDNA was isolated from Aspergillus
      giganteus strain MDH 18,894 and its expression in Escherichia coli was attempted
      by the use of both two-cistron and fusion protein-expression systems. Whereas the
      former resulted in low intracellular expression level of recombinant alpha-sarcin
      (r-Sar), the latter allowed high-level expression of the fusion protein in the
      culture supernatant. A variant form of alpha-sarcin with an additional threonine
      residue in position 1 (Thr-Sar) was obtained by proteolytic processing of the
      fusion protein with a final yield after purification of 40 mg/L of culture. Both
      recombinant proteins r-Sar and Thr-Sar were identical to native a-sarcin with
      respect to the biochemical properties and to the in vitro biological activity.

PMID- 9658389
TI  - Pulsed-field gel electrophoresis.
AB  - Pulsed-field gel electrophoresis (PFGE) was originally developed as a technique
      for providing electrophoretic karyotypes of micro-organisms. Since then the
      technique has evolved and diversified in many new directions. This review traces
      the evolution of PFGE, summarizes our understanding of its theoretical basis, and
      provides a comprehensive description of the methodology. Established and novel
      applications are explored and the reader is provided with an extensive list of
      references.

PMID- 9658390
TI  - Inducible gene expression systems in Lactococcus lactis.
AB  - Lactococcus lactis is industrially important microorganism used in many dairy
      fermentations. Numerous genes and gene expression signals from this organism have
      now been identified and characterized. Recently, several naturally occurring,
      inducible gene-expression systems have also been described in L. lactis. The main
      features of these systems can be exploited to design genetically engineered
      expression cassettes for controlled production of various proteins and enzymes.
      Novel gene-expression systems in Lactococcus have great potential for development
      of industrial cultures with desirable metabolic traits for a variety of
      bioprocessing applications.

PMID- 9658391
TI  - Fast atom bombardment mass spectrometric characterization of peptides.
AB  - Structural characterization of peptides in the range of 500-5000 Da, using fast
      atom bombardment (FAB) and Cs+ ion liquid secondary ion mass spectrometry (SIMS),
      is reviewed. These include synthetic peptides Kemptamide (mol wt 1516); GIF-C15
      (mol wt 1875), an isolated natural product as an acylated pentapeptide; and
      polypeptides generated from enzymatic digests of proteins. MS data is shown to
      reveal molecular weight and sequence information as well as determine disulfide
      bonds between cysteine residues and glycosylation sites in the case of a
      glycopeptide. The complementarity of MS technique to classical biochemical
      methods for peptide characterization is highlighted. The reader is briefly
      acquainted with two newer ionization techniques namely, electrospray ionization
      (ESI) and matrix-assisted laser desorption ionization (MALDI). Synthetic chemists
      and biochemists can refer to the in-depth review articles that are cited
      throughout this article.

PMID- 9658392
TI  - A simple method for the production of highly competent cells of Agrobacterium for
      transformation via electroporation.
AB  - The introduction of binary plasmids into Agrobacterium hosts for Agrobacterium
      mediated transformation of plants is most readily achieved by electroporation.
      However, occasionally, no transformed colonies are recovered and the
      transformation program is delayed. Poor transformation rates are commonly
      associated with particular combinations of Agrobacterium strains and plasmid
      selection markers. In order to avoid this problem, it is important for the
      bacteria to have a highly competent status for reception of plasmid DNA. It is
      also important to optimize the level of antibiotic for the selection of
      transformed colonies. In this article, we demonstrate that transformation
      competence is strongly related to the phase of growth at which a bacterial
      culture is prepared for electroporation, and we describe a simple procedure that
      allows the level of transformation-competent cells to be maximized. We have
      observed that there is significant variation between transformed Agrobacterium
      strains in the levels of antibiotic tolerance; we define the antibiotic levels
      that are appropriate for selection of three Argobacterium tumefaciens (EHA101,
      LBA4404, C58) and two Agrobacterium rhizogenes (LBA9402, Ar2626) strains,
      transformed with three alternative resistance markers (spectinomycin(res),
      kanamycin(res), and gentamycin(res)).

PMID- 9658393
TI  - Antisense therapy of hepatitis B virus infection.
AB  - Chronic infection with the hepatitis B virus (HBV) is a major health problem
      worldwide. The only established therapy is interferon-a with an efficacy of only
      30-40% in highly selected patients. The discovery of animal viruses closely
      related to the HBV has contributed to active research on antiviral therapy of
      chronic hepatitis B. The animal model tested and described in this article are
      Peking ducks infected with the duck hepatitis B virus (DHBV). Molecular
      therapeutic strategies aimed at blocking gene expression include antisense DNA.
      An antisense oligodeoxynucleotide directed against the 5'-region of the preS gene
      of DHBV inhibited viral replication and gene expression in vitro in primary duck
      hepatocytes and in vivo in Peking ducks. These results demonstrate the potential
      clinical use of antisense DNA as antiviral therapeutics.

PMID- 9658394
TI  - Recovering and reamplifying of the differentially expressed cDNA bands isolated
      from mRNA differential display. A modified method.
AB  - Methods for retrieving and reamplifying the differentially expressed cDNA bands
      have been modified. Direct reamplification of differentially expressed bands
      after cutting from a polyacrylamide gel (PAG) followed by a simple rinse and
      crush step has proved to be more convenient and effective than the traditional
      glycogen-precipitation method. Combination of 30 cycles of differential display
      (DD) polymerase chain reaction (PCR) and 20 cycles of standard PCR reaction also
      yielded higher reamplification rates.

PMID- 9658395
TI  - Half-embryo cocultivation technique for estimating the susceptibility of pea
      (Pisum sativum L.) and lentil (Lens culinaris Medik.) cultivars to Agrobacterium
      tumefaciens.
AB  - Longitudinally sliced embryonic axes from pea and lentil mature seeds
      cocultivated with A. tumefaciens carrying a gus reporter gene in its T-DNA
      provided a convenient means to evaluate the efficiency of gene transfer to
      tissues in different cultivars and cocultivation conditions. Use of this
      technique demonstrated wide variation in susceptibility to Agrobacterium among
      several pea and lentil commercial genotypes.

PMID- 9658396
TI  - Functional role of alternative splicing in pituitary P2X2 receptor-channel
      activation and desensitization.
AB  - Although ATP-gated ion channel (P2XR) expression is high among anterior pituitary
      cells, identification of the receptor subtypes and their selective expression
      within subpopulations of cell types, as well as their physiological role(s), are
      incompletely characterized. In this study, we focused on the expression and
      activity of the P2X2R subtype in anterior pituitary cells. Our results indicate
      that the primary P2X2R gene transcript in pituitary cells undergoes extensive
      alternative splicing, with generation of six isoforms. Two of these isoforms
      encode functional channels when expressed in GT1 or HEK293 cells: the wild-type
      P2X2R and the spliced isoform P2X2-2R, which lacks a stretch of carboxyl-terminal
      amino acids (Val370-Gln438). Four other clones showed different alterations,
      including an interfered reading frame starting in the first transmembrane domain
      and a 27-amino acid deletion in the large extracellular loop. When expressed
      separately or in combination with wild-type channels, these clones were
      nonfunctional. In single cell Ca2+ current and cytosolic Ca2+ concentration
      ([Ca2+)i) measurements, the P2X2R and P2X2-2R had similar EC50 values for ATP and
      time courses for activation and recovery from desensitization but differed
      significantly in their desensitization rates. The spliced isoform exhibited rapid
      and complete desensitization, whereas the wild-type channel desensitized slowly
      and incompletely. The mRNAs for wild-type and spliced channels were identified in
      enriched somatotroph, but not gonadotroph or lactotroph fractions. Expression of
      a functional ATP-gated channel in somatotrophs was confirmed by the ability of
      ATP to increase the frequency of [Ca2+]i spikes in spontaneously active cells or
      initiate spiking in quiescent cells. When voltage-gated Ca2+ influx was blocked,
      ATP increased [Ca2+]i, with a similar profile and EC50 to those observed in GT1
      cells heterologously expressing wild-type or spliced P2X2R. The ligand
      selectivity profile of native channels was consistent with the presence of P2X2R
      in somatotrophs. Finally, the desensitization rate of P2X2R in a majority of
      somatotrophs was comparable to that observed in neurons coexpressing wild-type
      and spliced channels. These data indicate that alternative splicing of P2X2R and
      coexpression of P2X2R and P2X2-2R subunits provide effective mechanisms for
      controlled cationic influx in somatotrophs.

PMID- 9658397
TI  - Determination of Gab1 (Grb2-associated binder-1) interaction with insulin
      receptor-signaling molecules.
AB  - The newly identified insulin receptor (IR) substrate, Gab1 [growth factor
      receptor bound 2 (Grb2)-associated binder-1] is rapidly phosphorylated on several
      tyrosine residues by the activated IR. Phosphorylated Gab1 acts as a docking
      protein for Src homology-2 (SH2) domain-containing proteins. These include the
      regulatory subunit p85 of phosphatidylinositol 3-kinase and phosphotyrosine
      phosphatase, SHP-2. In this report, using a modified version of the yeast two
      hybrid system, we localized which Gab1 phospho-tyrosine residues are required for
      its interaction with phosphatidylinositol 3-kinase and with SHP-2. Our results
      demonstrate that to interact with p85 or SHP-2 SH2 domains, Gab1 must be tyrosine
      phosphorylated by IR. Further, we found that Gab1 tyrosine 472 is the major site
      for association with p85, while tyrosines 447 and 589 are participating in this
      process. Concerning Gab1/SHP-2 interaction, only mutation of tyrosine 627
      prevents binding of Gab1 to SHP-2 SH2 domains, suggesting the occurrence of a
      monovalent binding event. Finally, we examined the role of Gab1 PH (Pleckstrin
      homology) domain in Gab1/IR interaction and in Gab1 tyrosine phosphorylation by
      IR. Using the modified two-hybrid system and in vitro experiments, we found that
      the Gab1 PH domain is not important for IR/ Gab1 interaction and for Gab1
      tyrosine phosphorylation. In contrast, in intact mammalian cells, Gab1 PH domain
      appears to be crucial for its tyrosine phosphorylation and association with SHP-2
      after insulin stimulation.

PMID- 9658398
TI  - Hormone-induced proliferation and differentiation of granulosa cells: a
      coordinated balance of the cell cycle regulators cyclin D2 and p27Kip1.
AB  - The proliferation and terminal differentiation of granulosa cells are critical
      for normal follicular growth, ovulation, and luteinization. Therefore, the in
      situ localization and hormonal regulation of cell cycle activators (cyclin D1,
      D2, and D3) and cell cycle inhibitors (p27Kip1 and p21Cip1) were analyzed in
      ovaries of mice and rats at defined stages of follicular growth and
      differentiation. Cyclin D2 mRNA was specifically localized to granulosa cells of
      growing follicles, while cyclin D1 and cyclin D3 were restricted to theca cells.
      In hypophysectomized (H) rats, cyclin D2 mRNA and protein were increased in
      granulosa cells by treatment with estradiol or FSH and were increased maximally
      by treatment with both hormones. In serum-free cultures of rat granulosa cells,
      cyclin D2 mRNA was rapidly elevated in response to FSH, forskolin, and estradiol,
      indicating that estradiol as well as cAMP can act directly and independently to
      increase cyclin D2 expression. The levels of p27Kip1 protein were not increased
      in response to estradiol or FSH. In contrast, when ovulatory doses of human CG
      (LH) were administered to hormonally primed H rats to stimulate luteinization,
      cyclin D2 mRNA and protein were rapidly decreased and undetectable within 4 h,
      specifically in granulosa cells of large follicles. Also in response to LH, the
      expression of the cell cycle inhibitor p27Kip1 was induced between 12 and 24 h
      (p21Cip1 was induced within 4 h) and remained elevated specifically in luteal
      tissue. A critical role for cyclin D2 in the hormone-dependent phase of
      follicular growth is illustrated by the ovarian follicles of cyclin D2-/- mice,
      which do not undergo rapid growth in response to hormones, but do express markers
      of FSH/LH action, cell cycle exit, and terminal differentiation. Collectively,
      these data indicate that FSH and estradiol regulate granulosa cell proliferation
      during the development of preovulatory follicles by increasing levels of cyclin
      D2 relative to p27Kip1 and that LH terminates follicular growth by down
      regulating cyclin D2 concurrent with up-regulation of p27Kip1 and p21Cip1.

PMID- 9658399
TI  - Progression of LNCaP prostate tumor cells during androgen deprivation: hormone
      independent growth, repression of proliferation by androgen, and role for p27Kip1
      in androgen-induced cell cycle arrest.
AB  - The molecular mechanism of androgen-independent growth of prostate cancer after
      androgen ablation was explored in LNCaP cells. An androgen-dependent clonal
      subline of the LNCaP human prostate carcinoma cell line, LNCaP 104-S, progressed
      to a slow growing stage (104-R1) and then to a faster growing stage (104-R2)
      during more than 2 yr of continuous culture in the absence of androgen. Androgen
      induced proliferation of 104-S cells is inhibited by the antiandrogen Casodex,
      while proliferation of 104-R1 and 104-R2 cells is unaffected by Casodex. This
      indicates that proliferation of 104-R1 and 104-R2 cells is not supported by low
      levels of androgen in the culture medium. Compared with LNCaP 104-S cells, both
      104-R1 and 104-R2 cells express higher basal levels of androgen receptor (AR),
      and proliferation of these two cell lines is paradoxically repressed by androgen.
      After continuous passage in androgen-containing medium, 104-R1 cells reverted
      back to an androgen-dependent phenotype. The mechanism of androgenic repression
      of 104-R1 and 104-R2 sublines was further evaluated by examining the role of
      critical regulatory factors involved in the control of cell cycle progression. At
      concentrations that repressed growth, androgen transiently induced the expression
      of the cyclin-dependent kinase (cdk) inhibitor p21waf1/cip1 in 104-R1 cells,
      while expression of the cdk inhibitor p27Kip1 was persistently induced by
      androgen in both 104-R1 and 104-R2 cells. Induced expression of murine p27Kip1 in
      104-R2 cells resulted in G1 arrest. Specific immunoprecipitates of Cdk2 but not
      Cdk4 from androgen-treated 104-R1 cells contained both p21waf1/cip1 and p27Kip1.
      This observation was confirmed by in vitro assay of histone H1 and Rb
      (retinoblastoma protein) phosphorylation by the proteins associated with the
      immune complex. Furthermore, inhibition of Cdk2 activity correlated with the
      accumulation of p27Kip1 and not p21waf1/cip1. From these results we conclude that
      androgenic repression of LNCaP 104-R1 and 104-R2 cell proliferation is due to the
      induction of p27Kip1, which in turn inhibits Cdk2, a factor critical for cell
      cycle progression and proliferation.

PMID- 9658400
TI  - Pituitary corticotroph SOCS-3: novel intracellular regulation of leukemia
      inhibitory factor-mediated proopiomelanocortin gene expression and
      adrenocorticotropin secretion.
AB  - As pituitary leukemia-inhibitory factor (LIF) mediates neuroimmune signals to the
      hypothalamo-pituitary-adrenal axis, we tested the role of intracellular SOCS-3 in
      corticotroph function. SOCS-3, a cytokine-inducible protein of the suppressor of
      cytokine signaling (SOCS) family, is expressed in the murine pituitary in vivo.
      After i.p. injection of LIF (5.0 micrograms/mouse) or interleukin-1 beta (0.1
      microgram/mouse) pituitary SOCS-3 mRNA was stimulated 9-fold and 6-fold,
      respectively. Also, in corticotroph AtT-20 cells LIF and interleukin-1 beta both
      potently stimulated SOCS-3 mRNA expression. In AtT-20 cells, stable
      overexpression of SOCS-3 inhibits basal and LIF-stimulated ACTH secretion in
      comparison to mock-transfected AtT-20 cells (basal: 4426 +/- 118 vs. 4973 +/- 138
      pg/ml, P < 0.05; LIF-induced: 5511 +/- 172 vs. 9308 +/- 465 pg/ml, P < 0.001).
      Stable overexpression of SOCS-3 cDNA in AtT-20 cells also resulted in a
      significant 50% decrease of LIF-induced POMC mRNA levels (P < 0.05) and POMC
      promoter activity (P < 0.001), respectively. Western blot analysis revealed an
      inhibition of LIF-stimulated gp130 and STAT-3 phosphorylation in SOCS-3
      overexpressing AtT-20 cells. Thus, SOCS-3 inhibits the Janus kinase (JAK) and
      signal transducers and activators of transcription (STAT) pathway, which is known
      to mediate LIF-stimulated ACTH secretion and POMC gene expression. In conclusion,
      SOCS-3 functions as an intracellular regulator of POMC gene expression and ACTH
      secretion, acting as a negative feedback mediator of the cytokine-mediated neuro
      immuno-endocrine interface.

PMID- 9658401
TI  - Atrial natriuretic peptide inhibits calcium-induced steroidogenic acute
      regulatory protein gene transcription in adrenal glomerulosa cells.
AB  - Atrial natriuretic peptide (ANP) is a potent inhibitor of mineralocorticoid
      synthesis induced in adrenal glomerulosa cells by physiological agonists
      activating the calcium messenger system, such as angiotensin II (Ang II) and
      potassium ion (K+). While the role of calcium in mediating Ang II- and K(+)
      induced aldosterone production is clearly established, the mechanisms leading to
      blockade of this steroidogenic response by ANP remain obscure. We have used
      bovine adrenal zona glomerulosa cells in primary culture, in which an activation
      of the calcium messenger system was mimicked by a 2-h exposure to an
      intracellular high-calcium clamp. The effect of ANP was studied on the following
      parameters of the steroidogenic pathway: 1) pregnenolone and aldosterone
      production; 2) changes in cytosolic ([Ca2+]c) and mitochondrial ([Ca2+]m) Ca2+
      concentrations, as assessed with targeted recombinant aequorin; 3) cholesterol
      content in outer mitochondrial membranes (OM), contact sites (CS), and inner
      membranes (IM); 4) steroidogenic acute regulatory (StAR) protein import into
      mitochondria by Western blot analysis; 5) StAR protein synthesis, as determined
      by [35S]methionine incorporation, immunoprecipitation, and SDS-PAGE; 6) StAR mRNA
      levels by Northern blot analysis with a StAR cDNA; 7) StAR gene transcription by
      nuclear run-on analysis. While clamping Ca2+ at 950 nM raised pregnenolone output
      3.5-fold and aldosterone output 3-fold, ANP prevented these responses with an
      IC50 of 1 nM and a maximal effect of 90% inhibition at 10 nM. In contrast, ANP
      did not affect the [Ca2+]c or [Ca2+]m changes occurring under Ca2+ clamp or Ang
      II stimulation in glomerulosa cells. The accumulation of cholesterol content in
      CS (139.7 +/- 10.7% of control) observed under high-Ca2+ clamp was prevented by
      10 nM ANP (92.4 +/- 4% of control). Similarly, while Ca2+ induced a marked
      accumulation of StAR protein in mitochondria of glomerulosa cells to 218 +/- 44%
      (n = 3) of controls, the presence of ANP led to a blockade of StAR protein
      mitochondrial import (113.3 +/- 15.0%). This effect was due to a complete
      suppression of the increased [35S]methionine incorporation into StAR protein that
      occurred under Ca2+ clamp (94.5 +/- 12.8% vs. 167.5 +/- 17.3%, n = 3).
      Furthermore, while the high-Ca2+ clamp significantly increased StAR mRNA levels
      to 188.5 +/- 8.4 of controls (n = 4), ANP completely prevented this response.
      Nuclear run-on analysis showed that increases in intracellular Ca2+ resulted in
      transcriptional induction of the StAR gene and that ANP inhibited this process.
      These results demonstrate that Ca2+ exerts a transcriptional control on StAR
      protein expression and that ANP appears to elicit its inhibitory effect on
      aldosterone biosynthesis by acting as a negative physiological regulator of StAR
      gene expression.

PMID- 9658402
TI  - FRA-1 expression level modulates regulation of activator protein-1 activity by
      estradiol in breast cancer cells.
AB  - We compared the effect of estradiol on activator protein-1 (AP-1) activity in
      estrogen receptor positive (ER alpha+) and estrogen receptor negative (ER alpha-)
      human breast cancer cell lines transiently transfected with the AP-1-responsive
      reporter plasmid AP-1-TK-CAT and an ER alpha expression vector. While estradiol
      increased AP-1 activity in the ER alpha+ cell lines MCF7, ZR75.1, and T47D, it
      decreased (MDA-MB231 and BT20 cells) or had no significant effect (MDA-MB435
      cells) on AP-1-mediated transcription in ER alpha- cells. Estradiol also
      inhibited AP-1 activity in ER alpha-MDA-MB231 cells stably transfected with ER
      alpha and in which ER alpha levels are close to those found in MCF7. Use of ER
      alpha mutant expression vectors demonstrated that the DNA-binding domain of ER
      alpha was needed for stimulation or inhibition of AP-1 activity by estradiol but
      suggested that ER alpha binding to estrogen-responsive elements was not required
      for these effects. Changes in regulation paralleled quantitative and qualitative
      changes in protein binding to AP-1 sites, as demonstrated by gel shift assay:
      protein binding was greater and DNA/protein complexes migrated faster for ER
      alpha--than for ER alpha+ cells. In fact, by Northern blot, a high level of Fra-1
      mRNA was found in BT20 and MDA-MB231 cells as compared with ER alpha+ cells, and
      MDA-MB435 cells showed an intermediary level of expression. The differential
      expression of Fra-1 in MCF7 and MDA-MB231 cells was confirmed at the protein
      level by supershift experiments. In addition, overexpression of Fra-1 in MCF7
      cells decreased the positive effect of estradiol while inhibition of Fra-1
      expression in MDA-MB231 cells, by transient transfection of the Fra-1 antisense
      expression vector, abolished the negative effect of the hormone. In conclusion,
      we demonstrated that ER alpha- breast cancer cell lines differ from ER+ cells by
      a high level of AP-1 DNA-binding activity due, at least in part, to high Fra-1
      constitutive expression. High Fra-1 concentration is crucial for the negative
      regulation of AP-1 activity by estradiol and thus may take part in estradiol
      induced inhibition of cell proliferation in ER alpha- breast cancer cells
      transfected with ER alpha expression construct.

PMID- 9658403
TI  - Calcium/calmodulin kinase inhibitors and immunosuppressant macrolides rapamycin
      and FK506 inhibit progestin- and glucocorticosteroid receptor-mediated
      transcription in human breast cancer T47D cells.
AB  - The effects of immunosuppressants and inhibitors of specific calcium/calmodulin
      kinase (CaMK) of types II and IV on progestin/glucocorticosteroid-induced
      transcription were studied in two human stably transfected breast cancer T47D
      cell lines. The lines contain the chloramphenicol acetyl transferase (CAT) gene
      under control either of the mouse mammary tumor virus promoter (T47D-MMTV-CAT),
      or the minimal promoter containing five glucocorticosteroid/progestin hormone
      response elements [T47D-(GRE)5-CAT]. Progestin- and triamcinolone acetonide (TA)
      induced CAT gene expression was inhibited in a dose-dependent manner in both
      lines by preincubation with rapamycin (Rap) and, to a lesser extent, with FK506,
      but not with cyclosporin A. CaMK II and/or IV inhibitors KN62 and KN93 also
      inhibited progestin- and TA-stimulated transcription in both lines. None of these
      drugs had any effect on basal transcription. The antagonist RU486 inhibited all
      the effects of both progestin and TA, suggesting that progesterone receptor (PR)
      , as well as glucocorticosteroid receptor (GR)- mediated transactivation are
      targets of immunosuppressants and CaMKs in T47D cells. Indeed, Northern analysis
      showed that Rap, KN62, and, to a lesser degree, FK506 inhibited progestin
      stimulation of Cyclin D1 mRNA levels, but not those of the non-steroid-regulated
      glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene. Addition of Rap or KN62
      after exposure of cells to progesterone agonist Org 2058 had no effect on
      induction of CAT activity. Taken together, these data indicate that Rap and
      FK506, as well as CaMK inhibitors, inhibit steroid-induced activities of
      exogenous, as well as of some endogenous, steroid receptor-regulated genes by a
      mechanism preceding hormone-induced receptor activation. Rap appeared to
      stabilize a 9S form of [3H]Org 2058-PR complexes isolated from T47D (GRE)5CAT
      cell nuclei. By contrast, the progesterone receptor (PR) was isolated from cells
      treated with KN62 as a 5S entity, undistinguishable from the 5S PR species
      extracted from cells treated with progestin only. The nuclear 9S-[3H]Org2058-PR
      resulting from cells exposed to Rap, contained, in addition to the heat shock
      proteins of 90 kDa and 70 kDa (hsp90 and hsp70), the FK506-binding immunophilin
      FKBP52 but not FKBP51, although the latter was part of unliganded PR
      heterocomplex associated with hsp90. These results suggest that Rap and KN62 act
      upon the PR by distinct mechanisms, with only Rap impeding progestin-induced PR
      transformation. FKBP51 appeared to dissociate from the receptor heterocomplex,
      but not from hsp90, after hormone binding to PR in vitro and in vivo, whether in
      the presence or not of Rap and KN62. Immunoprecipitation experiments
      distinguished two PR- and glucocorticosteroid (GR)-associated molecular chaperone
      complexes, containing hsp90 and hsp70 and FKBP52 or FKBP51. Another complex
      identified in T47D cytosol contained hsp90 and the cyclosporin A-binding
      cyclophilin of 40 kDa, CYP40, but not hsp70, PR, or GR. These observations
      support the concept that FKBP51 and FKBP52 can act as regulators of Rap and FK506
      activity upon PR and GR-mediated transcription, a mechanism that could be also
      regulated by type II and/or type IV CaMKs.

PMID- 9658404
TI  - Serotonergic repression of mitogen-activated protein kinase control of the
      calcitonin gene-related peptide enhancer.
AB  - We have investigated the mechanisms underlying regulation of the calcitonin gene
      related peptide (CGRP) cell-specific enhancer. Recently, we reported that this
      enhancer is inhibited by serotonin type-1 (5-HT1) agonists, similar to currently
      used antimigraine drugs. We have now tested whether this repression involves a
      mitogen-activated protein (MAP) kinase pathway. We first demonstrate that the
      CGRP enhancer is strongly (10-fold) activated by a constitutively active MAP
      kinase kinase (MEK1), yielding reporter activities 100-fold above the
      enhancerless control. The involvement of a MAP kinase pathway was confirmed by
      down-regulation of reporter activity upon cotransfection of a dominant negative
      Ras. Activation of the enhancer by MEK1 was blocked in a dose-dependent manner by
      the 5-HT1 receptor agonist CGS 12066A (CGS). Since it is not known whether the
      CGRP enhancer factors are immediate targets of MAP kinases, we then used EIk-1-
      and c-Jun-dependent reporter genes that are directly activated by the ERK
      (extracellular signal-regulated kinases) and JNK (c-Jun N-terminal kinase) MAP
      kinases. CGS treatment repressed the activation of both of these reporters,
      suggesting that at least two MAP kinases are the immediate targets of CGS
      mediated repression. We further demonstrate that 5-HT1 agonists inactivate ERK by
      dephosphorylation, even in the presence of constitutively activated MEK1. This
      inactivation appears to be due to a marked increase in the level of MAP kinase
      phosphatase-1. These results have defined a novel and general mechanism by which
      5-HT1 receptor agonists can repress MAP kinase activation of target genes, such
      as CGRP.

PMID- 9658405
TI  - The murine Dax-1 promoter is stimulated by SF-1 (steroidogenic factor-1) and
      inhibited by COUP-TF (chicken ovalbumin upstream promoter-transcription factor)
      via a composite nuclear receptor-regulatory element.
AB  - The Dax-1 gene encodes a protein that is structurally related to members of the
      orphan nuclear receptor superfamily. Dax-1 is coexpressed with another orphan
      nuclear receptor, steroidogenic factor-1 (SF-1), in the adrenal, gonads,
      hypothalamus, and pituitary gland. Mutations in Dax-1 cause adrenal hypoplasia
      congenita, a disorder that is characterized by adrenal insufficiency and
      hypogonadotropic hypogonadism. These developmental and endocrine abnormalities
      are similar to those caused by disruption of the murine Ftz-F1 gene (which
      encodes SF-1), suggesting that these nuclear receptors act along the same
      developmental cascade. Cloning of the murine Dax-1 gene revealed a candidate SF-1
      binding site in the Dax-1 promoter. In transient expression assays in SF-1
      deficient JEG-3 cells, SF-1 stimulated expression of the Dax-1 promoter. However,
      deletion or mutation of the consensus SF-1-binding site did not eliminate SF-1
      stimulation. Further analyses revealed the presence of a cryptic SF-1 site that
      creates an imperfect direct repeat of the SF-1 element. When linked to the
      minimal thymidine kinase promoter, each of the isolated SF-1 sites was sufficient
      to mediate transcriptional regulation by SF-1. Mutation of both SF-1 sites
      eliminated SF-1 binding and stimulation of the Dax-1 promoter. Unexpectedly,
      mutation of either half of the composite SF-1 sites increased basal activity in
      JEG-3 cells, suggesting interaction of a repressor protein. Gel shift analyses of
      the composite response element revealed an additional complex that was not
      supershifted by SF-1 antibodies. This complex was eliminated by mutation of
      either half-site, and it was supershifted by antibodies against chicken ovalbumin
      upstream promoter-transcription factor (COUP-TF). We propose that Dax-1 is
      stimulated by SF-1, and that SF-1 and COUP-TF provide antagonistic pathways that
      converge upon a common regulatory site.

PMID- 9658406
TI  - Dominant negative regulation by c-Jun of transcription of the uncoupling protein
      1 gene through a proximal cAMP-regulatory element: a mechanism for repressing
      basal and norepinephrine-induced expression of the gene before brown adipocyte
      differentiation.
AB  - The brown fat uncoupling protein-1 (ucp-1) gene is regulated by the sympathetic
      nervous system, and its transcription is stimulated by norepinephrine, mainly
      through cAMP-mediated pathways. Overexpression of the catalytic subunit of
      protein kinase A stimulated a chloramphenicol acetyltransferase expression vector
      driven by the 4.5-kb 5'-region of the rat ucp-1 gene. Mutant deletion analysis
      indicated the presence of the main cAMP-regulatory element (CRE) in the proximal
      region between -141 and -54. This region contains an element at -139/-122 able to
      confer enhancer and protein kinase A (PKA)-dependent activity to the basal
      thymidine kinase promoter. The potency of this element was much higher in
      differentiated than in nondifferentiated brown adipocytes. Gel shift analyses
      indicated that a complex array of proteins from brown fat nuclei bind to the 
      139/-122 element, among which CRE-binding protein (CREB) and Jun proteins were
      identified. In transfected brown adipocytes, c-Jun was a negative regulator of
      basal and PKA-induced transcription from the ucp-1 promoter acting through this
      proximal CRE region. A double-point mutation in the -139/-122 element abolished
      both PKA- and c-Jun-dependent regulation through this site, and overexpression of
      CREB blocked c-Jun repression. Thus, an opposite action of these two
      transcription factors on the -139/-122 CRE is proposed. c-Jun content in brown
      adipocytes differentiating in culture correlated negatively with both ucp-1 gene
      expression and the acquisition of the brown adipocyte morphology. These findings
      indicate that c-Jun provides a molecular mechanism to repress the basal and cAMP
      mediated expression of the ucp-1 gene before the differentiation of the brown
      adipocyte.

PMID- 9658407
TI  - Molecular cloning of xSRC-3, a novel transcription coactivator from Xenopus, that
      is related to AIB1, p/CIP, and TIF2.
AB  - Nuclear receptors regulate transcription by binding to specific DNA response
      elements of target genes. Herein, we report the molecular cloning and
      characterization of a novel Xenopus cDNA encoding a transcription coactivator
      xSRC-3 by using retinoid X receptor (RXR) as a bait in the yeast two-hybrid
      screening. It belongs to a growing coactivator family that includes a steroid
      receptor coactivator amplified in breast cancer (AIB1), p300/ CREB-binding
      protein (CBP)-interacting protein (p/ CIP), and transcriptional intermediate
      factor 2 (TIF2). It also interacts with a series of nuclear receptors including
      retinoic acid receptor (RAR), thyroid hormone receptor (TR), and orphan nuclear
      receptors [hepatocyte nuclear receptor 4 (HNF4) and constitutive androstane
      receptor (CAR)]. However, it does not interact with small heterodimer partner
      (SHP), an orphan nuclear receptor known to antagonize ligand-dependent
      transactivation of other nuclear receptors. In CV-1 cells, cotransfection of xSRC
      3 differentially stimulates ligand-induced transactivation of RXR, TR, and RAR in
      a dose-dependent manner. Interestingly, xSRC-3 is highly expressed in adult liver
      and early stages of oocyte development, suggesting that studies of xSRC-3 may
      lead to better understanding of the roles nuclear receptors play in oocyte
      development as well as liver-specific gene expression.

PMID- 9658408
TI  - Expression cloning of a novel estrogenic mouse 17 beta-hydroxysteroid
      dehydrogenase/17-ketosteroid reductase (m17HSD7), previously described as a
      prolactin receptor-associated protein (PRAP) in rat.
AB  - 17 beta-Hydroxysteroid dehydrogenases/17-ketosteroid reductases (17HSDs) modulate
      the biological activity of certain estrogens and androgens by catalyzing
      reductase or dehydrogenase reactions between 17-keto- and 17 beta
      hydroxysteroids. In the present study, we demonstrate expression cloning of a
      novel type of 17HSD, chronologically named 17HSD type 7, from the HC11 cell line
      derived from mouse mammary gland. The cloned cDNA, 1.7 kb in size, encodes a
      protein of 334 amino acids with a calculated molecular mass of 37,317 Da. The
      primary structure contains segments characteristic of enzymes belonging to the
      short-chain dehydrogenase/reductase superfamily. Strikingly, mouse 17HSD type 7
      (m17HSD7) shows 89% identity with a recently cloned rat protein called PRL
      receptor-associated protein (PRAP). The function of PRAP has not yet been
      demonstrated. The enzymatic characteristics of m17HSD7 and RT-PCR-cloned rat PRAP
      (rPRAP) were analyzed in cultured HEK-293 cells, where both of the enzymes
      efficiently catalyzed conversion of estrone (E1) to estradiol (E2). With other
      substrates tested no detectable 17HSD or 20 alpha-hydroxysteroid dehydrogenase
      activities were found. Kinetic parameters for m17HSD7 further indicate that E1 is
      a preferred substrate for this enzyme. Relative catalytic efficiencies (Vmax/K(m)
      values) for E1 and E2 are 244 and 48, respectively. As it is the case with rPRAP,
      m17HSD7 is most abundantly expressed in the ovaries of pregnant animals. Further
      studies show that the rat enzyme is primarily expressed in the middle and second
      half of pregnancy, in parallel with E2 secretion from the corpus luteum. The mRNA
      for m17HSD7 is also apparent in the placenta, and a slight signal for m17HSD7 is
      found in the ovaries of adult nonpregnant mice, in the mammary gland, liver,
      kidney, and testis. Altogether, because of their similar primary structures,
      enzymatic characteristics, and the tissue distribution of m17HSD7 and rPRAP, we
      suggest that rPRAP is rat 17HSD type 7. Furthermore, the results indicate that
      17HSD7 is an enzyme of E2 biosynthesis, which is predominantly expressed in the
      corpus luteum of the pregnant animal.

PMID- 9658409
TI  - Truncated SNAP-25 (1-197), like botulinum neurotoxin A, can inhibit insulin
      secretion from HIT-T15 insulinoma cells.
AB  - We and others have previously shown that insulin-secreting cells of the pancreas
      express high levels of SNAP-25 (synaptosomal-associated protein of 25 kDa), a 206
      amino acid t-SNARE (target soluble N-ethylmaleimide-sensitive factor attachment
      protein receptors) implicated in synaptic vesicle exocytosis. In the present
      study, we show that SNAP-25 is required for insulin secretion by transient
      transfection of Botulinum Neurotoxin A (BoNT/A) into insulin-secreting HIT-T15
      cells. Transient expression of BoNT/A cleaved the endogenous as well as
      overexpressed SNAP-25 proteins and caused significant reductions in K+ and
      glucose-evoked secretion of insulin. To determine whether the inhibition of
      release was due to the depletion of functional SNAP-25 or the accumulation of
      proteolytic by-products, we transfected cells with SNAP-25 proteins from which
      the C-terminal nine amino acids had been deleted to mimic the effects of the
      toxin. This modified SNAP-25 (amino acids 1-197) remained bound to the plasma
      membrane but was as effective as the toxin at inhibiting insulin secretion.
      Microfluorimetry revealed that the inhibition of secretion was due neither to
      changes in basal cytosolic Ca2+ levels nor in Ca2+ influx evoked by K(+)-mediated
      plasma membrane depolarization. Electron microscopy revealed that cells
      transfected with either BoNT/A or truncated SNAP-25 contained significantly
      higher numbers of insulin granules, many of which clustered close to the plasma
      membrane. Together, these results demonstrate that functional SNAP-25 proteins
      are required for insulin secretion and suggest that the inhibitory action of
      BoNT/A toxin on insulin secretion is in part caused by the production of the
      plasma membrane-bound cleavage product, which itself interferes with insulin
      granule docking and fusion.

PMID- 9658411
TI  - Dyslexia, neurolinguistic ability, and anatomical variation of the planum
      temporale.
AB  - This article addresses the relationship between patterns of planum temporale
      symmetry/asymmetry and dyslexia and neurolinguistic abilities. Considerable
      research indicates that dyslexic individuals typically do not display the
      predominant pattern of leftward planum temporale asymmetry. Variable findings on
      the structural basis of symmetry are due partially to measurement issues, which
      are examined in some detail in this critical review. The physiological basis of
      symmetry may be reduced neuronal elimination in the right planum, although other
      alternatives are offered. Theories are offered to explain how symmetrical plana
      are related to dyslexia, and it is evident that symmetrical plana are not
      sufficient to produce dyslexia. However, some evidence suggests that nonleftward
      plana asymmetry is associated with deficits in verbal comprehension, phonological
      decoding, and expressive language. It is concluded that nonleftward asymmetry is
      associated with linguistic deficits, but that explanatory theories need to be
      further developed. Among the many issues that need to be addressed, future
      research needs to determine whether the relationship between patterns of planum
      temporale symmetry/asymmetry and linguistic ability is specific to dyslexia or if
      asymmetry covaries lawfully with linguistic abilities in nondyslexic populations.

PMID- 9658410
TI  - Neuropsychological aspects of multiple sclerosis.
AB  - Since S. Rao's ["Neuropsychology of Multiple Sclerosis: A Critical Review," A
      Journal of Clinical and Experimental Neuropsychology, Vol. 85, pp. 503-542]
      (1986) seminal review, considerable research has been undertaken on the
      neuropsychological consequences of multiple sclerosis. This review incorporates
      the research literature of the last decade in presenting an overview of the
      current state of our knowledge concerning the etiology, course, symptoms,
      assessment, consequences, and treatment of multiple sclerosis (MS). The concept
      of subcortical dementia is revisited in light of the most recent literature
      documenting the neuropsychological deficits in patients with MS. The view that
      cognitively heterogeneous patient groups may disguise more specific patterns of
      focal neuropsychological impairment is considered. A critical review of the
      recent literature is also presented, detailing the degree to which recent
      research has addressed the areas of research need identified by Rao in 1986.
      Given recent advances in our knowledge, the need for more attention to be
      directed toward the evaluation of rehabilitation and psychological intervention
      is highlighted.

PMID- 9658413
TI  - [Immediate and late arrhythmia in patients operated on for tetralogy of Fallot].
AB  - Arrhythmias are a frequent complication after repair of tetralogy of Fallot
      (TOF). We present our experience with 97 patients with special consideration for
      early and late hyperkynetic arrhythmias. The most frequent, 4% of the patients,
      was in junctional tachycardia. Late arrhythmias can be atrial or ventricular. The
      incidence of ventricular arrhythmias in the literature range from 42 to 82%. In
      the Authors experience multiforme ventricular ectopy was present in 80% of the
      patients, 20 years after surgery. We suggest an exercise test and averaging ECG
      in all the patients. Thirty six percent of patients with supraventricular
      tachycardia were symptomatic. CONCLUSION: as the incidence of arrhythmias after
      correction of TOF is high, it is very important to periodically reassess these
      patients. Antiarrhythmic treatment is indicated in all symptomatic patients,
      especially in those with major arrhythmias (SVT, AF and VT).

PMID- 9658412
TI  - Depression after mild traumatic brain injury: a review of current research.
AB  - Research pertaining to the occurrence of depression and/or depression
      symptomatology after a Mild Traumatic Brain Injury (MTBI) was reviewed. We found
      that methodological differences such as the criteria used to assess MTBI and
      depression, time that elapsed since brain injury, and control group variations
      confounded comparisons across studies. Nevertheless, the studies are consistent
      with at least a 35% prevalence of, and left frontal damage with depression after
      MTBI, an overlap of symptoms of depression and Postconcussion Syndrome (PCS), and
      indicate that depression can continue for many years following the injury. Our
      conclusion is that MTBI is the triggering event for a set of pathophysiological
      changes and a concomitant depressive episode in a vulnerable subset of the
      population. Due to a paucity of research, it cannot be definitively concluded
      that the underlying substrates of depression seen after MTBI and clinical
      depression are the same. Implications for future investigations are discussed.

PMID- 9658414
TI  - Early and late atrial dysrhythmias after modified Fontan operation.
AB  - Occurrence of supraventricular tachycardia and sinus node dysfunction was
      investigated pre- and postoperatively by serial ECG and Holter monitors in 63
      consecutive patients with univentricular circulation after modified Fontan
      operation (total cavopulmonary connection 39 patients, atriopulmonary connection
      24 patients). Mean age at operation was 7.2 (0.1-20.3) years. Of the 63 patients,
      14 (22%) had early (< 14 d) supraventricular tachycardia or sinus node
      dysfunction, which was not related to the type of operation. None of 9 patients
      with a preoperative mean right atrial pressure < or = 2.5 mm Hg had early
      supraventricular tachycardia or sinus node dysfunction in contrast to 16/54
      patients (30%) with a preoperative mean right atrial pressure > 2.5 mm Hg. 6/63
      patients died during the early (< 14 d) postoperative period. In only 1 child,
      death was related to a dysrhythmia (junctional ectopic tachycardia). During a
      mean follow-up of 2.5 years, 15/57 long-term survivors (21%) had late
      supraventricular tachycardia or sinus node dysfunction. Early supraventricular
      tachycardia/sinus node dysfunction was a predictor or late atrial dysrhythmias,
      as it occurred in 8 of the surviving 14 patients with early dysrhythmias in
      contrast to 4 children without early atrial dysrhythmias (p < or = 0.001). After
      creation of an atriopulmonary connection, 10/22 patients (45%) had late
      supraventricular tachycardia/sinus node dysfunction, but only 2/35 patients (6%)
      with a total cavopulmonary connection had late atrial dysrhythmias (p < 0.001).
      CONCLUSIONS: Early atrial dysrhythmias after the Fontan operation were related to
      preoperative hemodynamics. Early supraventricular tachycardia/sinus node
      dysfunction and the atriopulmonary type of Fontan connection were significant
      risk factors for late atrial dysrhythmias.

PMID- 9658415
TI  - [Probioticss, prebiotics,synbiotics and eubiotics].
AB  - The Author summarizes the most widely definitions of agents affecting the
      intestinal ecosystem. Probiotic is a live microbial feed which beneficially
      affects the intestinal microbial balance. Prebiotic is a non digestible food
      which improves the growth of bacteria in the colon. Synbiotic or eubiotic is a
      mixture of probiotics and prebiotics.

PMID- 9658416
TI  - [Determination of brain death in Intensive Pediatric Therapy].
AB  - The subject of this paper is to report our experience in the determination of
      brain death in infants and children. We have retrospectively examined the
      incidence of brain death occurred in 504 consecutive children admitted to
      multidisciplinary pediatric ICU at "Bambino Gesu" Hospital of Rome during the
      years 1994 to 1997. According to current Italian Law, brain death was declared in
      8 children (1.6%), whose primary diagnoses were: Meningitis (3 cases);
      nontraumatic intracerebral hemorrhage (2 cases); medulloblastoma (1 case); brain
      metastasis of neuroblastoma (1 case); SIDS (1 case). All brain death diagnoses
      were made using clinical criteria and confirmatory tests. A difficult problem was
      met in achieving the required Pa-CO2 values higher than 60 mmHg without unduly
      lowering O2 saturation. In order to obtain easily this objective we have recently
      switched the ventilator to intermittent mandatory volume ventilation at a rate of
      five stroke per minute using a FiO2 of 1 before starting the apnea test. In
      infants younger than one year the required cerebral circulatory arrest was
      documented in the pericallosal artery by doppler ultrasonography performed
      through the fonticuli cranii. The absence of cerebral blood flow was recorded for
      one to five days after clinical and electroencephalographic diagnosis of brain
      death, causing an unnecessary prolonged rianimative support. This also confirms
      that in young infants brain death may occur without a marked increase of
      intracranial pressure. Last, but not least, we believe that particular attention
      must be paid to psycho-emotional conditions of parents as well as of intensivists
      and nurses especially when brain death must be assessed in children.

PMID- 9658417
TI  - [Incidence of ROP (Retinopathy of Prematurity) in hypoxemic neonates: case
      contribution].
AB  - In this retrospective study the Authors correlated the hypoxia with the severity
      of retinopathy of prematurity (ROP) in a population of 683 outborn preterm
      infants (bw < 2500 g and gestational age < 38 weeks). They excluded all cases
      with specific pathological conditions. Among neonates with the same gestational
      age the incidence of ROP was higher (p < .05) in those with hypoxia (pH < 7.25,
      tcPO2 < 50 mmHg). These data suggest that hypoxia plays a role in the
      pathogenesis of ROP.

PMID- 9658418
TI  - [Cardiac involvement in tuberous sclerosis in the first months of life:
      physiopathologic and clinical aspects of cardiac rhabdomyoma].
AB  - Cardiac rhabdomyomas are frequent in association with tuberous sclerosis and they
      are the first symptoms of Bourneville disease in fetal and neonatal period.
      Clinical findings of cardiac rhabdomiomas are quite heterogeneous: asymptomatic,
      cardiac murmur, cardiomegaly, heart failure or arrhythmias. Echocardiography can
      determine site, dimensions, numbers and haemodynamic consequences of cardiac
      tumours and their clinical evolution at follow-up. In this study the Authors
      report clinical findings in 9 cases of cardiac rhabdomyomas in newborn infants: 3
      has familiarity for tuberous sclerosis and two of these had prenatal
      echocardiographic diagnosis; in the other 6 cases diagnosis was casual (1 in
      fetal period). All patients with prenatal diagnosis were asymptomatic. In other
      cases 1 had extrasystolic arrhythmias and five had only cardiac murmurs.
      Echocardiographic follow-up (6 months to 5 years) showed regression of number and
      dimension of cardiac masses in all cases. In 7 cases cardiac rhabdomiomas were
      associated with tuberous sclerosis.

PMID- 9658419
TI  - [Long-term effects of combined therapy in patients with beta-thalassemia major].
AB  - We evaluated therapy complications in 19 beta-thalassemia major patients (mean
      age from 3 years/5 months and 1 years/6 months) who were followed at II Pediatric
      Department-University of Bari. 3 out of 19 patients underwent allogenic BMT from
      matched related donor; 2 out of 19 underwent splenectomy. All of them were
      receiving hypertransfusion therapy and continuous chelation with DFO. In all
      patients we performed physical examination, laboratory assays, cardiac and
      endocrinologic function tests, serum HBV-HCV-HIV antibodies, otoscopy and
      audiometric test, fundus oculi, skeletal x-ray. 1 out of 19 patients, who was
      under 15, had a slight dilatation of left ventricle and arythmia. All patients
      were HBsAb positive. 4/19 patients were HCV Ab positive (ELISA test) with an
      increase in ALT-AST serum levels since at least 6 months. In 3 of them we
      assessed RIBA test, always positive. 3 of them underwent liver biopsy (1 iron
      overload 2 chronic active hepatitis). All patients were HIV Ab negative. 4/15
      patients revealed low GH levels after Arginina test. 13 pre-pubescent patients
      had normal results with GNRH test but lower results after FSH test. 1 pubescent
      patient had gonadotropic hypophyseal deficit. 4 patients had subclinic
      hypothiroidism. We couldn't find any sequelas in bone-eyes-ears. Hypertransfusion
      therapy, chelation, profilaxis of infections improved length and quality of life
      in thalassemic patients. Hypogonadotropic hypogonadism remains a serious sequela
      and we think it needs to be treated.

PMID- 9658420
TI  - [Dyspneic bronchopathy and asthma: hospital admission between 1979 and 1994].
AB  - 4,618 children, hospital admitted between 1979 and 1994 for wheezy bronchitis or
      asthma, have been investigated. the patients were distributed in two groups,
      according to mean age of 19 months or 8 year. An increasing incidence of asthma,
      an earlier onset or respiratory symptoms, more frequent hospitalisation in
      children aging less than 2 years, in recent years were observed. In elder
      children however, less frequent hospitalisation occurred.

PMID- 9658421
TI  - [Anxiety and memory in hospitalized adolescents; effect of the projection of a
      film].
AB  - The purpose of our study was the evaluation of the effects of a film on the
      anxiety and memory of cronically ill adolescents (n. 25) versus healthy
      adolescents (n. 25). The chronic illness was: renal failure, renal
      transplantation (6 months before), scoliosis and Crohn's disease. The S.T.A.I.-Y
      test was administered before and after the film to evaluate the state-anxiety
      before and after the vision, only the trait-anxiety was evaluated before. The
      state and trait-anxiety was not abnormal, although the state anxiety was
      increased in the hospitalized adolescents before the vision (mean S.T.A.I.-Y =
      43.2) and was decreasing (mean S.T.A.I.-Y = 37.32) after it. This result confirms
      the needs of a global paediatric health-care in order to minimise psychosocial
      traumas, associated with hospitalisation. The second goal of our research was the
      mood and memory correlation and the mood-congruency. We administered two memory
      tests (free and guided) using a recorder and a questionnaire. Our study presents
      a better free-memory in healthy subjects (16.6% vs. 5.16% in the hospitalized
      adolescents) and a better guided-memory in the healthy subjects (13.7% vs. 7.08%
      in the hospitalized adolescents). Our results can't confirm the mood-congruency
      theory, although the study conclusion is concerning a general decreasing of
      memory competence, following the repeated hospital admissions and the chronic
      illness.

PMID- 9658422
TI  - [Use of a Gore-Tex patch in the primary repair of congenital defects of the
      anterior abdominal wall].
AB  - The surgical treatments for large omphaloceles and gastroschisis have to avoid a
      dangerous primary fascial closure when it's not feasible, so the pediatric
      surgeon can use staged surgical procedures that achieve a gradual increase in
      size of the abdominal cavity. Therefore, a staged approach is mandatory to avoid
      a complicated reduction and it's the best treatment for large congenital
      abdominal wall defects. Gore-Tex soft tissue is easy to handle, pliable, soft and
      well tolerated, so Gore-Tex patch closure is a safe and good alternative to
      staged repair in large omphaloceles and gastroschisis. The Authors report about
      five newborns with large congenital abdominal wall defects, in whom primary
      fascial closure could not be accomplished, so they were successfully treated by
      primary repair with Gore-Tex patch. The Authors also describe the surgical
      technique and they reconsider the last surgical techniques for large omphaloceles
      and gastroschisis.

PMID- 9658423
TI  - [Use of radionuclides in the evaluation of intestinal transit time in children
      with idiopathic constipation].
AB  - Colonic transit times, in patients with chronic idiopathic constipation, in the
      past were estimated using radiopaque markers. Currently they are evaluated with
      colonic scintigraphy, which employs 111In DTPA orally, added to the usual
      children's breakfast in a 0.05 mCi dose. Anterior views of the abdomen are
      obtained at 6th, 24th, 30th, 48th, 54th, 72nd hour using a gamma camera on a 128
      x 128 matrix and stored on hard disk. These images are processed in successive
      times, and the colon is divided in three main segments: right-, left- and recto
      sigmoid-colon. Total and segmental percentage retentions are evaluated in each
      interval time. 58 children (35 males and 23 females), aged 1-12 years (mean
      8.13), referred for chronic idiopathic constipation at Pediatric Surgery
      Department of Siena, were studied between January 1990 and September 1996. This
      group was compared with a control group formed by 15 patients (9 males and 6
      females) aged 3-14 years (mean 8.53). Cutoff values, obtained in this control
      group, allowed us to distinguish, among the 58 children with idiopathic
      constipation, 6 symptomatic patients with normal colonic transit times and 52
      symptomatic patients with pathologic ones. In this last group the evaluation of
      segmentary colonic transit times allowed us to identify 13 patients (25%) with
      increased right colonic transit time, 19 (36.5%) with increased left colonic
      transit time and 20 (38.5%) with increased recto-sigmoidal colonic transit time.
      Statistical survey allowed to distinguish significantly pathological subjects
      from control group ones.

PMID- 9658424
TI  - [Neonatal buprenorphine withdrawal syndrome, what is the right therapy?].
AB  - Buprenorphine is a new substance now widely used in detoxification of heroin
      addicts. In this report we describe the case of a newborn baby who suffered from
      a neonatal withdrawal syndrome characterized by a severe and prolonged course.
      This syndrome was followed by marked symptoms of impaired neurological
      development and by epilepsy. The ineffectiveness of methadone in relieving
      withdrawal symptoms from buprenorphine and its potential dangerous effects in
      this case are also outlined, whereas the efficacy of therapy with phenobarbytal
      is stressed. We think that this case is noteworthy, since the widespread use of
      buprenorphine among drug addicts will probably provoke an increase in the number
      of cases of buprenorphine withdrawal syndrome in the next years.

PMID- 9658425
TI  - [Schoenlein-Henoch purpura following Kawasaki syndrome: a predisposition to
      vasculitis?].

PMID- 9658426
TI  - [Urinary hydrometrocolpos by persistent urogenital sinus; prenatal diagnosis and
      neonatal management].
AB  - Urogenital Sinus (UGS) malformation can be ascribed to an arrest of normal
      embryonic vaginal development. Neonates with UGS frequently have ambiguous
      genitalia, rarely the vulva may be normal. The aim of this work is to define the
      role of prenatal sonography in the diagnosis of UGS associated with hydrocolpos
      and/or hydrometrocolpos. The Authors report their experience on 3 cases of UGS
      without ambiguous genitalia with hydrometrocolpos, in which prenatal sonography
      had shown a cystic dilatation in the pelvis. After birth the 3 neonates presented
      with female genitalia and a single orifice between the labia. The pelvis
      sonography showed in all the cases an hydrometrocolpos with a large vagina and a
      compressed and anteriorly located bladder. Voiding cystourethrogram, genitography
      and genitoscopy confirmed the presence of an UGS with urinary retention inside
      the vagina and stenosis of the distal portion of the vagina itself. An early
      drainage of the capacious vagina was performed in the three patients. There are
      very few reports in the literature of UGS with hydrometrocolpos diagnosed in
      utero. The cystic dilatation of the vagina is always misdiagnosed with a
      distended bladder. In utero, infact, the bladder can not be identified being
      displaced anteriorly by the vagina. The presence of a fluid-debris level inside
      the cystic anechoic mass must be considered a crucial finding. Multiple echoes
      are due to vaginal secretions. Prenatal ultrasound has then a definitive role in
      detecting an obstructed genital tract. This allows to rapidly drain the vagina
      relieving urinary tract obstruction.

PMID- 9658428
TI  - [The pediatrician and multiple sclerosis].

PMID- 9658427
TI  - [An unusual case of macroscopic hematuria in pediatric age].
AB  - An unusual case of macroscopic hematuria in a 14 year old boy is presented. At
      the time of the first hospital admission, no urinary tract infection could be
      demonstrated, in spite of the associated symptoms of stranguria and dysuria. At
      ultrasound examination, only a mild thickening of the upper bladder wall was
      detected, and cystoscopy showed a huge oedema and inflammation of the mucosal
      layer. The biopsy of the bladder was characterized by a definite eosinophilic
      infiltration; due to this particular hystologic pattern, the diagnosis of
      eosinophilic cystitis was made. In the following months, the boy did not improve.
      Recurrent hematuria occurred, and a pseudo-polypoid mass in the inner bladder
      wall was detected at ultrasonography. A limited resection of the vesical dome was
      performed, to remove completely the mass. The hystologic examination showed
      Schistosoma Haematobium eggs in the bladder wall, with a typical granulomatous
      reaction. The post-operative course was uneventful, and the child was completely
      cured after Praziquantel treatment. The Authors underline the need to take into
      account Schistosomiasis in cases of hematuria, particularly when this symptom
      affects boys coming from countries where Bilharziasis is endemic.

PMID- 9658429
TI  - Pediatric hematology and oncology at the Heinrich-Heine University Medical
      School, Dusseldorf, Germany.
AB  - The Heinrich-Heine University Medical Center is a large tertiary care hospital, a
      major medical research facility, the largest teaching hospital of the Heinrich
      Heine University Medical School, and a training facility for both nursing and
      physiotherapy schools. In 1974, the Department of Pediatric Hematology and
      Oncology was established as a separate department within the University's Center
      of Child Health, serving a catchment area of 3 million inhabitants in the
      northwest of the federal state of Northrhine-Westfalia. With approximately 85
      newly diagnosed cases of malignant illness and 25 bone marrow transplantations
      per annum, the department is one of the larger ones in Germany. The self
      understanding of this unit reaches beyond immediate care of patients, however.
      The department attempts to provide psychosocial support to families, patients,
      and caregivers. Furthermore, it takes its responsibility as a teaching and
      research facility quite seriously, aiming to add to our understanding of cancer
      with the goal of improving the outcome of childhood cancer.

PMID- 9658430
TI  - Successful multimodal therapy for kaposiform hemangioendothelioma complicated by
      Kasabach-Merritt phenomenon: case report and review of the literature.
AB  - We present the management challenge provided by a patient with kaposiform
      hemangioendothelioma associated with Kasabach-Merritt phenomenon. A female child
      presented at 14 months of age with an ecchymotic swelling of her right upper arm
      and axilla. Subsequently, she developed profound thrombocytopenia and
      hypofibrinogenemia (Kasabach-Merritt phenomenon). Biopsy of the lesion revealed
      kaposiform hemangioendothelioma, which has been reported as the predominant
      pathologic diagnosis associated with Kasabach-Merritt phenomenon. To achieve
      involution of the lesion and preserve function of the arm, the following
      interventions were involved: embolization, systemic interferon, cyclophosphamide,
      epsilon aminocaproic acid, and compression therapy. The clinical management of
      this patient was formidable until we arrived at the proper combination of
      therapies. Multimodal intervention may be required to manage fastidious
      hemangioendotheliomas of childhood, achieve clinical improvement, and prevent
      further morbidity.

PMID- 9658431
TI  - Aseptic osteonecrosis in children with acute lymphoblastic leukemia.
AB  - Joint destruction caused by aseptic osteonecroses (AONs) is a severe complication
      in acute lymphoblastic leukemia (ALL). Here, factors were determined that
      influence the occurrence and clinical course of AON in ALL patients. Clinical
      data of 121 patients were correlated with the occurrence of AON. Magnetic
      resonance imaging was performed in patients with bone pain. Areas of AONs were
      correlated with the clinical course of AON. Ten patients presented with clinical
      symptoms of AON and 9 of 10 patients were graded as high-risk ALL compared with
      46 of 111 patients without AON (chi 2, P < .05). In 10 ALL patients 66 AONs were
      identified by MRI. In some patients up to 14 different AON sites were observed.
      The courses of AONs varied in individual patients, suggesting that necrosis
      specific factors might be responsible. A size above 900 mm2 was significantly
      associated with progressive AON (P < .01). The more intensive treatment regimen
      in high-risk ALL patients might contribute to the development of AON. The
      clinical course of AON, however, is determined by necrosis-specific factors such
      as a large size. These data could help in developing therapeutic strategies for
      the prevention of progressive AON.

PMID- 9658432
TI  - Impact of high-dose cytosine arabinoside in poor-prognosis acute lymphoblastic
      leukemia: Cancer Institute experience, Chennai, India.
AB  - High-dose cytosine arabinoside (HD-AraC) has been used in relapsed and refractory
      cases of acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL).
      Sixty-two poor-prognosis ALL patients were treated with HD-AraC between 1983 and
      1995 at the Cancer Institute, Chennai, India. Of them, 37 had experienced a
      relapse, 16 were partial responders (refractory) to the induction regimen, and 9
      were high risk due to central nervous system or testicular involvement or total
      counts above 200,000/mm3 at presentation. Of the 37 patients with relapses, 22
      (59.5%) achieved complete remission (CR) and 10 had no evidence of disease (NED);
      of the 16 refractory group patients, 10 achieved CR and 2 had NED; and of the 9
      high-risk patients, 5 had NED at the end of the study. The 5-year event-free
      survival (EFS) values of relapsed, refractory and high-risk group categories were
      21.7%, 12.5%, and 55.6%, with a mean duration of 41 months, 18 months, and 85
      months, respectively. Total alopecia and grade IV myelosuppression were the
      predominant toxicities. HD-AraC is an effective drug in the treatment of relapsed
      and refractory acute leukemias and can overcome relative drug resistance in high
      concentrations.

PMID- 9658433
TI  - Detection of antiphospholipid antibodies in children and adolescents.
AB  - The prevalence of antiphospholipid antibodies (APAs) has not yet been studied in
      children and adolescents with various diseases. We assayed plasma samples of 203
      children and adolescents, aged 0.1 to 21 years (median 6 years), by enzyme-linked
      immunosorbent assay detecting immunoglobulin G (IgG) and IgM antibodies directed
      against cardiolipin, phosphatidylserine, and phosphatidic acid. According to
      their diagnosis children were divided into five groups: 10 patients with
      autoimmune and autoimmune-like diseases (group I); 88 patients with infections
      (group II); 20 patients with metabolic diseases (group III); 65 children with
      various other diseases (group IV); 20 healthy children without physical illnes
      (group V). Results were compared for statistical significance using Fisher's
      exact test. APAs were found in 65 of 203 patients. In all groups of patients the
      prevalence of APAs was increased compared with healthy children. The highest
      prevalence of APAs was found in patients with autoimmune or autoimmune-like
      diseases or infections. Thrombosis did not occur in children with increased APA
      levels. In 4 of 65 patients with detectable APAs bleeding was observed. However,
      three of these four children had additional coagulation abnormalities. We
      conclude that in children and adolescents increased APA titers may occur in a
      variety of diseases. The frequency of APA-related symptoms is low.

PMID- 9658434
TI  - Pharmacokinetic analysis of vancomycin in steady state in pediatric cancer
      patients.
AB  - Thirty children suffering from different types of malignancies, neutropenic
      fever, and suspected staphylococcal bacteremia were evaluated for the
      pharmacokinetics of vancomycin in steady-state conditions and compared with eight
      children suffering from proven methicillin-resistant staphylococcal infection.
      All the studied population received intravenous vancomycin at 40 mg/kg daily
      divided into four daily doses. The individual pharmacokinetic parameters were
      calculated using a one-compartment model for two blood vancomycin samples. The
      mean (+/- SD) half-time (t1/2, hours), clearance (L/h/kg), Vss (L/kg), Cmax
      (microgram/mL), and Cmin (microgram/mL) were 10.5 (7.9) and 14.9 (9.1) hours;
      0.11 (0.14) and 0.06 (0.06) L/h/kg; 0.62 (0.33) and 1.3 (0.6) L/kg; 28.3 (11.8)
      and 22.3 (9.8) micrograms/mL; and 5.7 (6.0) and 7.4 (4.8) micrograms/mL for the
      malignancy and control groups, respectively. The malignancy group had a
      significantly shorter t1/2 (P = .005), higher clearance (P = .005), and lower
      Cmin (P = .03) in comparison with the control group. It is suggested that the
      prescription of vancomycin at 40 mg/kg daily, divided into four daily doses, is
      safe and will provide a peak blood level of vancomycin sufficient to cover the
      broad spectrum of staphylococcal bacteria. The vancomycin dose should be
      individualized, based on an individual pharmacokinetic profile.

PMID- 9658435
TI  - Effects of intra-articular vitamin E and corticosteroid injection in experimental
      hemarthrosis in rabbits.
AB  - The effects of intra-articular injections of vitamin E and corticosteroid were
      investigated in skeletally mature New Zealand white rabbits in which experimental
      hemarthrosis was induced for 14 days. The rabbits were divided into three groups
      composed of eight rabbits each: the first group comprised of animals with
      hemarthrosis, the second group animals with hemarthrosis and intra-articular
      injections of 20 mg vitamin E, and the third group animals with hemarthrosis and
      intra-articular injections of 10 mg of triamcinolone acetonide (TCA).
      Proteoglycan levels in the joint cartilage of the hemarthrosis group were found
      to be increased significantly compared with the controls (P < .01), whereas in
      the vitamin E-injected group they were significantly decreased (P < .05). In the
      TCA-injected group, proteoglycan levels were not found to be significantly
      different from those in the hemarthrosis group (P > .05). Histopathological
      evaluation showed that the cartilage structure in the joint of the control limbs
      was identical to that in the vitamin E- and TCA-injected limbs. In the
      hemarthrosis group, in comparison with the controls, the joint surface was
      roughened and fibrillated. In the superficial areas of the cartilage tissue,
      chondrocytes were decreased in number. These findings suggest that in this model,
      vitamin E and TCA may be helpful in preventing the joint cartilage changes seen
      in hemarthrosis.

PMID- 9658436
TI  - Epstein-Barr virus-associated lymphoproliferative disorder after unrelated bone
      marrow transplantation in a young child with Wiskott-Aldrich syndrome.
AB  - We report a case of a 16-month-old Wiskott-Aldrich syndrome (WAS) patient with a
      WASP gene mutation who received human leukocyte antigen (HLA)-matched, unrelated
      allogeneic bone marrow transplantation (BMT) followed by an Epstein-Barr virus
      associated lymphoproliferative disorder (EB-LPD), diagnosed by clinical findings,
      polymerase chain reaction detection of the EB virus genome, and spontaneous
      lymphocyte proliferation of donor cell origin. EB-LPD is one of frequent lethal
      complications in HLA-mismatched or unrelated BMT in this syndrome. Adoptive
      immunotherapy with donor leukocyte transfusion, including appropriate numbers of
      CD3-positive T cells, was effective for the EB-LPD, achieving almost complete
      recovery 1 year later without any findings of graft-versus-host disease.

PMID- 9658437
TI  - Evans' syndrome in a child with diabetes mellitus.
AB  - A patient suffering from infantile-onset insulin-dependent diabetes mellitus is
      reported in whom immune pancytopenia (Evans' syndrome) developed at the age of 2
      1/2 years. Hepatosplenomegaly, chronic lymphadenopathy, and elevated levels of
      immunoglobulins G and M were also present. The course of Evans' syndrome was
      fatal in this patient. The association of Evans' syndrome with other immune
      disorders is discussed.

PMID- 9658438
TI  - Analysis of thrombopoietin and c-mpl expression in a child with essential
      thrombocythemia.
AB  - The pathogenesis of the increased number of megakaryocytes and thrombocytosis in
      essential thrombocythemia (ET) is still unknown. We examined the expression of c
      mpl, a receptor of thrombopoietin (TPO), and its signaling molecules in a patient
      with ET. An 8-year-old girl showed a high platelet count and an increased number
      of bone marrow megakaryocytes. Neither chromosomal abnormalities nor
      myelofibrosis was observed. Following the diagnosis of ET, aspirin therapy was
      begun for the patient, with only modest improvement of symptoms. Her platelet
      count ranged from 1,200,000/microL to 2,200,000/microL for more than 2 years. In
      the analyses, the serum TPO level in the patient was 420 attomoles/mL (normal,
      760 +/- 320). The level of c-mpl expression in bone marrow mononuclear cells was
      higher in the patient than in healthy children, while there was no difference in
      the level of c-mpl expression in CD34+ cells, indicating an expanded pool of
      megakaryocytic lineage cells. The level of Janus kinase 2 (Jak2) expression was
      lower in the patient than in a healthy child. These findings indicate that the
      signal pathway mediated by c-Mpl after binding to TPO may be impaired in ET.
      Further analysis is needed to clarify the mechanism underlying the development of
      thrombocytosis in ET patients.

PMID- 9658439
TI  - Ocular involvement and visual sequelae in hemophagocytic lymphohistiocytosis in
      association with congenital dyfsfibrinogenemia.
AB  - We report a 7-year-old girl with hemophagocytic lymphohistiocytosis and an
      uncommon complication of vascular retinopathy and visual sequelae. She was also
      verified to be complicated with dysfibrinogenemia. The patient was treated with
      etoposide, dexamethasone, and cyclosporin A. During the fifth hospital week, a
      generalized tonic-clonic convulsion developed followed by deep coma. When she
      regained full consciousness, she complained of a visual disturbance. The
      ophthalmologic examination showed bilateral extensive retinal edema with numerous
      cotton-wool spots, indicative of vaso-occlusive retinopathy. This is inconsistent
      with the main finding of previous cases with ocular involvement, namely
      papilledema. Severely reduced visual acuity and visual field defects remained in
      both eyes even after systemic therapy. An awareness of this rare but serious
      complication is important because it may be preventable by early institution of
      chemotherapy. The pathogenesis of the retinopathy is also discussed.

PMID- 9658440
TI  - Serum superoxide dismutase levels of beta thalassemia patients and effects of
      high dosage of intravenous desferrioxamine treatment on superoxide dismutase
      levels.

PMID- 9658441
TI  - Glucose-6-phosphate dehydrogenase levels in the newborn.

PMID- 9658442
TI  - Ethnoveterinary medicines used for ruminants in Trinidad and Tobago.
AB  - Ethnoveterinary research was conducted in Trinidad and Tobago in 1995, in order
      to document existing ethnoveterinary practices. This paper describes 20 medicinal
      plants used to treat ruminants. The main plants used were Azadirachta indica and
      Curcuma longa. Medicinal plants were used predominantly for endoparasites,
      internal and external injuries and pregnancy-related conditions. A 4-stage
      process was used to conduct the research and document the ethnoveterinary
      practices. This documentation could provide a foundation for the further
      scientific study and verification of those practices which merit such study.

PMID- 9658443
TI  - Risk factors for false-positive serological reactions for bovine brucellosis in
      Saone-et-Loire (France).
AB  - Since 1990, unusually high rates of false-positive serological reactions (FPSR)
      in bovine brucellosis screening have been observed in some countries of the
      European Union. The aim of this survey was to describe this phenomenon in a
      highly affected French Department, and to evaluate the links between some
      individual or herd factors and the occurrence of these FPSR. Before 1990, low
      backgrounds of FPSR were recorded (individual prevalence rate: less than 0.5 per
      10,000). The phenomenon burst during the 1990-91 screening campaign, reached a
      peak in 1992-93 (50.5 per 10,000), and then decreased until the last studied
      campaign, 1995-96 (9.1 per 10,000). The phenomenon was transient and sporadic
      within a herd. At the herd-screening level, four assumed risk factors were
      isolated: (i) the probability of a herd-screening to be positive was closely and
      positively linked with the herd screening size; (ii) during a given screening
      campaign, the prevalence of FPSR decreased from December to November; (iii) the
      presence of at least one goat on the premises increased the risk for the 1992-93
      and 1993-94 screening campaigns; and (iv) a previous FPSR in a given herd
      appeared to be a weak but significant risk factor. At the individual-animal
      level, herd size, sex and breed did not seem to be linked with FPSR appearance,
      while young animals were significantly more affected than older ones. However,
      global variations in herd or individual prevalences remained unexplained. The
      lack of link between FPSR and brucellosis is strengthened. The hypothesis of a
      widely spread causal agent with a low individual host susceptibility and/or a low
      probability of detecting FPSR animals can be supported by these results.

PMID- 9658444
TI  - A Reed-Frost model of the spread of tuberculosis within seven Swedish extensive
      farmed fallow deer herds.
AB  - The within-herd transmission of tuberculosis, after introduction of infection,
      was evaluated in seven Swedish herds of farmed fallow deer. The evaluation was
      based on a subset of data obtained from a previous epidemiological investigation,
      comprising 13 tuberculosis-infected deer herds, with the purpose of tracing the
      source of infection. A computer spreadsheet model based on the Reed-Frost method
      was developed to estimate the number of new infections. For each herd, a k-value
      (the number of effective contacts made by an individual during a time period) was
      estimated through fitting the model to the observed incidence in each herd. We
      concluded that, despite the relatively short observation periods and uncertain
      tuberculosis incidence estimates for the observed herds, the k's obtained could
      be used to quantify the estimated spread of tuberculosis in extensive deer herds
      in Sweden.

PMID- 9658445
TI  - An epidemiological study of calcium metabolism in non-paretic postparturient
      Holstein cows.
AB  - Data from 1021 lactations of non-paretic Holstein cows followed in 14 Quebec
      dairy herds were used to describe calcium 'metabolism' after calving in healthy
      cows. Serum total calcium, phosphorus, magnesium, potassium, albumin, and glucose
      were measured on the first and seventh days post-calving. The distributions were
      described and compared between the first and seventh day postpartum. The
      relationships between serum calcium on the one hand and the other serum
      metabolites and the cow's age on the other hand were assessed using a general
      linear model. Serum calcium and phosphorus values were lower on the first day
      postpartum than a week later (2.03 +/- 0.26 vs 2.26 +/- 0.18 mmol/l, 1.78 +/-
      0.48 vs 1.93 +/- 0.39 mmol/l, respectively), whereas it was the opposite for
      glucose, magnesium, and potassium (3.98 +/- 0.95 vs 3.12 +/- 0.60 mmol/l, 1.01 +/
      0.35 vs 0.95 +/- 0.13 mmol/l, 4.84 +/- 0.40 vs 4.69 +/- 0.38 mmol/l,
      respectively). Albumin values were similar (25.7 +/- 3.3 vs 25.2 +/- 3.4 g/l). On
      the first day postpartum, serum calcium was associated in a curvilinear fashion
      with age, phosphorus and albumin. It also was associated, but to a lesser extent,
      with glucose and magnesium, whereas it was not associated with potassium. On the
      seventh day postpartum, calcium was associated with age, phosphorus and with an
      increased importance of albumin. The results are discussed with regard to
      postpartum hypocalcemia, the interpretation of serum metabolite values after
      calving, and the use of the physiological stress at calving. We concluded that
      (1) postpartum hypocalcemia was an event to be expected, especially for the older
      cow, (2) a multivariable approach should be used to interpret biochemical
      profiles after calving, and (3) such profiles could be used to better assess the
      cow's health.

PMID- 9658446
TI  - Ivermectin treatment did not increase slaughter weight of first-year reindeer
      calves.
AB  - To investigate if antiparasitic treatment of reindeer calves during the summer
      could increase their carcass weight during the slaughter period in autumn and
      winter, 529 reindeer calves were allocated to three groups, weighed, and marked
      with individually numbered plastic ear tags in early July, 1995. One of the
      groups was left untreated, another was treated with ivermectin injection at 200
      micrograms/kg, and the third with pour-on ivermectin at 500 micrograms/kg.
      Following slaughter, carcass weights were received from 231 animals, and there
      was no difference between the treatment groups.

PMID- 9658447
TI  - Risk factors for the presence of antibodies to Toxoplasma gondii in Norwegian
      slaughter lambs.
AB  - In a study of lambs from 194 sheep flocks from different areas of Norway, 44.3%
      of the flocks were found seropositive against Toxoplasma gondii using an ELISA
      test, with antibodies found in 16.2% of the 1940 individual animals. The risk
      factors for the occurrence of antibodies to Toxoplasma gondii found in the
      multivariate logistic regression were: daily presence of a young cat in the sheep
      house (Odds ratio, OR = 4.11, 95% CI = 1.01-19.7); 'atypical' grazing of lambs
      (OR = 6.35, CI = 2.36-17.11); use of mouse poison in the sheep house (OR = 2.26,
      CI = 1.02-5.00); farm situated at an altitude > 100 meters above seal level (101
      250 m: OR = 1.20, CI = 0.49-2.92; 251-500 m: OR = 4.97; CI = 2.04-12.0; > 500 m:
      OR = 3.66, CI = 1.33-10.1). A lower risk was found for flocks with perforated
      metal floors in the sheep house (OR = 0.47, CI = 0.23-0.96) and timber
      construction of the sheep house (OR = 0.34, CI = 0.15-0.80). Based on these
      findings it was recommended that farmers avoid keeping young cats in the sheep
      houses, that close-to-farm grazing be kept to a minimum and that perforated metal
      floors be used in the sheep houses. However, with such a high seroprevalence, the
      proposed measures alone would not reduce the occurrence of Toxoplasma in lambs to
      a level where undercooked lamb can be consumed without posing an unacceptable
      risk for some consumer groups.

PMID- 9658448
TI  - Theoretical and clinical aspects: an overview.

PMID- 9658449
TI  - Rhythms of experience: the interplay of symmetry and asymmetry in development.

PMID- 9658450
TI  - Primitive mental states: early affective processes and symmetrization.

PMID- 9658451
TI  - Infinity and the limits of the unconscious.

PMID- 9658452
TI  - Writing in.

PMID- 9658453
TI  - Psychoanalysis, paradigm shift, and theoretical reflexivity: the case of the
      Oedipus complex.

PMID- 9658454
TI  - Gender configurations: relational patterns in heterosexual, lesbian, and gay male
      couples.

PMID- 9658455
TI  - The van Gogh family: a study in alienation.

PMID- 9658456
TI  - [Role of the extracellular matrix in X-chromosome-linked muscular dystrophy:
      immunohistochemical study].
AB  - OBJECTIVE: To study the role of the extracellular matrix in the pathogenesis of
      the X-linked muscular dystrophy. MATERIAL AND METHODS: Muscle specimens from 8
      normal controls with ages ranging from 4 to 14 years of age and those of 14 X
      linked muscular dystrophy patients were studied by means of polyclonal antibodies
      able to recognize extracellular matrix molecules. The findings of each of the
      controls and patients were evaluated systematically using a semiquantitative
      morphological method. On the other hand, with the help of an automatic
      interactive image analyzer, the following structures were measured: a) area
      occupied by the perimysium; b) area of the endomysium, and c) transverse fibre
      area. RESULTS: The deposition of the extracellular matrix components of patients
      with X-linked muscular dystrophy is a selective phenomenon which is mostly
      related to groups of fibers undergoing necrosis-regeneration. X-linked muscular
      dystrophy patients have an heterogeneous clinical and pathological picture. At
      one end of the spectrum there are patients with the most severe phenotype, in
      which reduction of fiber size, early deposition of connective tissue and
      distortion of the capillary bed are the most conspicuous pathological changes. At
      the other end muscle fiber hypertrophy and splitting, lesser connective tissue
      deposition and a milder clinical course predominate. Selective deposition of
      extracellular matrix components occurs at each point of the spectrum. The
      distribution of the extracellular matrix components does not appear to accomplish
      a substitutive function designed to replace the loss of number or volume of the
      muscle fibers.

PMID- 9658457
TI  - [Gamma-sarcoglycanopathy: clinico-pathological and genetic study of 11 cases].
AB  - INTRODUCTION: Limb Girdle Muscular Dystrophy type 2C (LGMD2C) is an autosomal
      recessive dystrophy due to the deficit of gamma-sarcoglycan, one of the proteins
      of the dystrophin-associated proteins complex (DAP). A new mutation in the gamma
      sarcoglycan gene, 13q12, has been described recently and is exclusive of the
      gypsy community. OBJECTIVE: To describe the clinicopathological and the genetic
      findings of eleven cases from a Spanish gypsy family with LGMD2C and the mutation
      C283Y. MATERIAL AND METHODS: We describe a large gypsy family with the C283Y
      mutation and eleven affected patients. We have performed an extensive clinical
      and pathological study with immunohistochemistry and Western blot analyses in the
      eleven patients and a genetic study of a total of twenty-seven members of the
      family. RESULTS: The patients presented a severe muscular dystrophy with a
      dystrophic pattern in the muscle biopsy, normal immunolabeling for dystrophin,
      very weak for alpha-, beta- and delta-sarcoglycan and absent for gamma
      sarcoglycan. These eleven patients were found to be homozygous for the mutation
      and twelve other members of the family, heterozygous. CONCLUSIONS: The clinical
      picture and the evolution of the disease herein described is similar to that
      observed in DMD. Two fundamental differences were found: the autosomal recessive
      mode of inheritance, and the normal immunohistochemistry and immunoblot for
      dystrophin in the skeletal muscle.

PMID- 9658458
TI  - [3-hydroxy-3-methylglutaric aciduria and recurrent Reye-like syndrome].
AB  - INTRODUCTION: 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMG-CoA
      lyase) is an inborn error of ketogenesis and Leucine catabolism. HMG-CoA lyase
      catalyses the final step in leucine degradation, converting HMG-CoA to acetyl-CoA
      and acetoacetic acid. Clinical manifestations include hepatomegaly, lethargy or
      coma and apnoea. Biochemically there is a characteristic absence of ketosis with
      hypoglycemia, acidosis, hipertransaminasemia and variable hyperammoniemia. The
      urinary organic acid profile includes elevated concentrations of 3-hydroxy-3
      isovaleric, 3-hydroxy-3-methylglutaric, 3-methylglutaconic and 3-methylglutaric
      acids. CLINICAL CASE: Here, we report the case of a 17-year-old girl who
      presented in both ten months and five years of age a clinical picture
      characterized by lethargy leading to apnea and coma, hepatomegaly, hypoglycemia,
      metabolic acidosis, hyperammoniemia, elevated serum transaminases and absence of
      ketonuria. Diagnostic of Reye syndrome was suggested by hystopathologic finding
      of hepatic steatosis and clinical and biochemical data. As of 11 years old,
      laboratory investigations revealed carnitine deficiency and characteristic
      aciduria. Confirmatory enzyme diagnosis revealing deficiency of HMG-CoA lyase was
      made in cultured fibroblasts. CONCLUSION: Our report constitutes an example of
      the presentation of HMG-CoA lyase deficiency as recurrent Reye-like syndrome.

PMID- 9658459
TI  - [Behavioral evaluation of the unilateral lesion model in rats using 6
      hydroxydopamine. Correlation between the rotations induced by D-amphetamine,
      apomorphine and the manual dexterity test].
AB  - INTRODUCTION: Evaluation of rotatory activity induced by dopaminergic agonists is
      the most widely used test of conduct for the measurement of dopaminergic
      depletion of a unilateral lesion of the striatonigral pathway caused by 6
      hydroxydopamine (6-OHDA) in rats, since it is quantitatively related to the
      extension of the dopaminergic denervation. OBJECTIVE: The objective of this study
      was to evaluate, from different angles, the changes in conduct seen in the model
      of unilateral lesion with 6-OHDA and to establish correlation with the rotation
      induced by D-amphetamine and by apomorphine and the ladder test. MATERIAL AND
      METHODS: Male Wistar rats were used. Lesions were produced in the SNpc by
      stereotactic injection of 6-OHDA into the right hemisphere and the effectiveness
      of the lesions was studied using the rotary conduct induced by D-amphetamine and
      apomorphine. The motor ability of the front legs was measured by the ladder test,
      carried out under standard and forced conditions. RESULTS: All the animals with
      lesions had difficulty in reaching food with both legs, although the most
      pronounced deficit was in the leg contralateral to the lesion. The ladder test
      correlated better with rotatory activity induced by apomorphine than by D
      amphetamine. CONCLUSION: The animals with most dopamine loss showed most
      deficient use of their front legs.

PMID- 9658460
TI  - [Frontal lobe epilepsy in infancy: is there a benign partial frontal lobe
      epilepsy?].
AB  - INTRODUCTION: Only the organic and cryptogenic forms of frontal lobe epilepsy
      have been admitted by the ILAE, but according to several reports in the
      literature, it probably exists also an idiopathic form, at present not well
      recognized. OBJECTIVE: To study the differences between the organic and the
      cryptogenic forms of frontal epilepsy in our patients, that might indicate the
      presence of idiopathic cases within the presumed cryptogenic group. MATERIAL AND
      METHODS: All patients diagnosed of frontal lobe epilepsy, EEG registered, at the
      neuropediatric clinic of our hospital during 1993-1996, were selected: 30
      patients under 14 years of age that were classified as organic (10 cases) or
      cryptogenic (20 cases) according to CT or MRI findings. The Mann-Whitney test and
      the Fisher exact test were performed for statistical analysis. Five patients with
      peculiar neurocognitive symptoms, epilepsy-related, are described in detail.
      RESULTS: Significative differences between the organic and cryptogenic forms of
      frontal lobe epilepsy were not found except for the tendency of cryptogenic EEG
      foci to spread beyond the frontal lobe, to generalize and to be associated with
      foci of other localizations. Epileptic status, either convulsive or not
      convulsive, were a frequent complication in both groups. CONCLUSIONS: The
      identification of an idiopathic form of frontal lobe epilepsy is difficult by its
      low prevalence as compared to the cryptogenic and organic forms, by the tendency
      of frontal seizures to become epileptic status, which predicts an intractable
      epilepsy, and by the clinical characteristics essential to frontal discharges:
      heterogeneity, frequent impairment of consciousness and specially the
      neurocognitive semiology, including dementia, that occurs as a critic or
      paracritic phenomenon, and that sometimes may develop or be accentuated by
      antiepileptic medication.

PMID- 9658461
TI  - [Electroencephalogram findings in lesionectomies: preliminary results].
AB  - INTRODUCTION: Use of the electrocorticogram (EcoG) in planning lesionectomies is
      a controversial subject at present. MATERIAL AND METHODS: We describe a series of
      5 patients with epileptic crises, 3 with arteriovenous malformations in whom the
      lesion was completely resected, followed by postoperative angiography, and two
      with gliomas with low grade malignancy in whom iridium 192 was implanted.
      RESULTS: 1. The most frequent reason for consultation was convulsions. 2. In our
      series of patients the commonest site was the frontal zone of the right
      hemisphere. 3. Potentials with epileptiform characteristics were registered at
      the edges of the lesions and occasionally over the lesion itself. In two cases
      electro-clinical crises were seen. 4. The lesions were resected from normal
      tissue independently of the EcoG results. CONCLUSION: Although they are
      preliminary findings, the results of the study support the usefulness of this
      technique to guide the surgical procedures used for the treatment of intractable
      epilepsy.

PMID- 9658462
TI  - [Blood levels of soluble ICAM-1 in patients with multiple sclerosis].
AB  - INTRODUCTION: Multiple sclerosis (MS) is a chronic inflammatory disease of the
      central nervous system. The Intercellular Adhesion Molecule plays a fundamental
      part in the migration of T cells to the inflammed tissues. It is known that there
      is an increase in the expression of endothelial cells and other cells found in
      lesions of the central nervous system of MS patients. ICAM-I may be detected in
      its soluble form in serum and it is of interest to understand its behaviour in
      this liquid since it is easily accessible. MATERIAL AND METHODS: We studied the
      concentration of soluble ICAM-I in the serum of patients with MS: one group which
      had clinical attacks were studied whilst in remission; another had the chronic
      progressive clinical form and a third group had optic neuritis as the probable
      initial sign of the disorder. Within the different clinical forms, some patients
      received treatment with beta-interferon or azathioprine and others did not.
      RESULTS AND CONCLUSIONS: We found a significant increase in the levels of soluble
      ICAM-I in patients with inactive, untreated MS as compared with normal persons,
      with no difference found between the different clinical types.

PMID- 9658463
TI  - [Impact of fatigue in multiple sclerosis: study of a population-based series in
      Valladolid].
AB  - INTRODUCTION: Fatigue is one of the commonest findings in multiple sclerosis (MS)
      although it has scarcely been investigated as an independent symptom. OBJECTIVE:
      To evaluate the effect of fatigue in a population based series of patients with
      MS and to analyze its relation to other clinical variables. METHODS: A
      descriptive, transverse study based on a geographically defined population.
      Fatigue was measured using the Krupp scale in 48 patients with definite clinical
      MS. We analyzed the relation between the degree of fatigue and sex, age of onset,
      age at the time of the study, type of evolution, index of progression of
      disability, duration of illness and degree of impairment according to the
      Expanded Disability Status Scale (EDSS) and neurological functional systems.
      RESULTS: 64.6% of the patients had a significant degree of fatigue. Of these, 90%
      considered fatigue to be one of the three most disabling symptoms of their
      illness. There was no difference between men and women in their perception of
      fatigue. The patients with progressive illness, of greater age and those with
      higher EDSS scores had more fatigue. This aspect was not affected by age of
      onset, duration of illness nor index of progression. CONCLUSIONS: Fatigue should
      be evaluated as an independent symptom of MS. Evaluation using specific scales
      may contribute to better understanding of the physiopathology and investigation
      of more effective treatment.

PMID- 9658464
TI  - [Brain lesions of perinatal and late prenatal origin in a neuropediatric
      context].
AB  - INTRODUCTION: The obstetric and neonatal technological advances have changed the
      frequency and syndromic classification of perinatal brain lesions. OBJECTIVE: To
      study all prevalent patients during 1996, with perinatal or late intrauterine
      brain lesions, in the outpatient neuropediatric clinic at our hospital. METHODS:
      Selection of patients according to neuroimaging findings, and/or neurological
      sequela with documented perinatal antecedent. EXCLUSION CRITERIA: a normal MRI,
      brain lesions of doubtful origin, or uncertain sequela with normal CT or
      echography studies. Descriptive study, and also analytical, using logistic
      regression to study the relationship between antecedents and sequela. RESULTS: A
      total of 111 patients with: brain lesions due to hypoxic-ischemic encephalopathy
      (22 cases), lesions due to prematurity (29), late intrauterine infection or
      neonatal meningitis as the only cause of fixed neurological impairment (12),
      unexpected vascular brain lesions during the neonatal period (11), late
      intrauterine brain lesions (37). The neurological sequela observed were: cerebral
      palsy (68%), epilepsy (47%), mental retardation (45%), learning disorders in
      (34%) of those of school age and free from mental retardation, strabism (26%),
      microcephaly (19%), visual impairment (14%), hyperkinesis (10%). The neuroimaging
      findings were: focal lesions (45%), hydrocephaly (28%), intraventricular
      haemorrhage (22%), white matter lesions (24%), venous thrombosis (2%). The
      multivariable analysis showed, as the most noticeable finding, the relationship
      between the antecedent of mechanical ventilation and late development of
      hyperkinesis (OR: 10), in this sample of patients with severe sequela. Three
      patients should be noted: a case of late-onset dystonia secondary to a late
      intrauterine brain lesion, a child with exclusively cerebellar symptoms due to a
      destructive cerebellar lesion of prenatal onset, and a patient with an acquired
      perinatal biopercular lesion and pseudobulbar palsy as the only long-term
      sequelae.

PMID- 9658465
TI  - [Electromyographic diagnosis of 772 patients in the Mostoles Hospital].
AB  - INTRODUCTION AND OBJECTIVE: There are few references in the literature to
      demographic data of the disorders most frequently studied by electromyography.
      Our objective was to obtain a demographic description of the patients usually
      sent to us for electromyographic studies. MATERIAL AND METHODS: Descriptive and
      analytical assessment was done of 914 electromyographic diagnoses seen in a
      sample of 722 patients sent to Mostoles Hospital, referral centre of Health
      District VIII of the Community of Madrid with an estimated population of 407,836
      inhabitants, for conventional electroneurographic and electromyographic studies
      between May 1995 and February 1996. We recorded data regarding electromyographic
      diagnosis, localization, intensity, whether the study was for diagnostic purposes
      or follow-up, medical centre referring the patient, medical speciality sending
      the patient, clinical impression, age and sex. RESULTS: The commonest pathology
      seen was carpal trapping of the median nerve, both in men and in women (three
      times more frequent in women). There was an estimated incidence of 136 cases per
      year per 100,000 women and 36 cases per year per 100,000 men (most frequent in
      patients aged 20-70, with a maximum frequency in those in their fifties). There
      was marked right sided predominance. The commonest pathology in men was
      polyneuropathy, with an estimated incidence of 80 cases per 100,000 men and 72
      cases per 100,000 women. This was the commonest diagnosis in the patients aged
      over 70. Mononeuropathy of the legs was most commonly seen in men and in the
      first twenty years of life.

PMID- 9658466
TI  - [Neuro-ophthalmological alternations in patients with pituitary adenomas and
      intrasellar arachnoidocele].
AB  - INTRODUCTION, MATERIAL AND METHODS: We studied 103 patients with hypophyseal
      tumors aged between 15 and 74, with a marked predominance of females. Results. Of
      these, 49 patients were diagnosed as having macroadenomas (47.5%), 27 with
      microadenomas (26.2%), 25 with arachnoidoceles (24.3%) and two with
      craniopharyngiomas (1.9%). Of the total there were 78.9% functioning tumors of
      which the commonest was prolactinoma. CONCLUSIONS: Kinetic and static perimetry
      complement each other as diagnostic methods to obtain information about damage to
      the visual pathway caused by these tumors.

PMID- 9658467
TI  - [Kinsbourne syndrome: review of our cases].
AB  - INTRODUCTION: The childhood opsoclonus-myoclonus or Kinsbourne syndrome, is a
      uncommon process, of acute or subacute beginning, which affects infant and
      children. It's course is characterized by opsoclonus, polimyoclonias and
      cerebellar ataxia. The disease is frequently associated to neuroblastoma (46%).
      MATERIAL AND METHODS: We present a retrospective study on 9 patients, emphasizing
      the clinical presentation and the evolution aspects. RESULTS AND CONCLUSIONS: We
      found changes in the EEG in three cases. Most surprising is the scarce incidence
      of neuroblastoma, which has been found only in a one out of nine patients. We
      found three cases with relapse during the treatment or on withdrawal and one of
      them relapsed twice again. The evolution has been variable, since 5/9 patient
      have presented some type of mild or moderate neuro-psychological sequelae. Out of
      three patient with relapses, two presented permanent neurological sequelae. A
      patient which suffered three relapses, is also the one which presents more
      serious sequelae.

PMID- 9658468
TI  - [Characteristics of sleep in deafness].
AB  - INTRODUCTION, MATERIAL AND METHODS: We studied a profoundly deaf population, in
      order to evaluate the zeitgeber sleep role of the ambient sound. A closed
      questionnaire was given to 36 students at a special college for the profoundly
      deaf and to 321 controls of similar age and sex. RESULTS: We do not find total
      upset of sleep, but a good sleep quality, probably due to the noise isolation of
      the deafness. We find some traces of insecurity in falling asleep. CONCLUSION:
      The ambient sound do not seem to play an important role as a sleep-wake
      zeitgeber.

PMID- 9658469
TI  - [Variability of the Boston test for the diagnosis of aphasia in active working
      adults].
AB  - INTRODUCTION: The aim of this study was to analyze the influence of age, gender,
      socioeconomic status (SES), academic achievement (education), and type of
      occupation, on the performance of the Boston Diagnostic Aphasia Examination
      (BDAE) Spanish version. MATERIAL AND METHODS: The BDAE was administered to a
      group of 156, 19 to 60 years old, occupationally active normal subjects. RESULTS:
      A descriptive analysis showed that some subjects (1 to 3%) scored in the
      pathological range of the centiles and profiles of the BDAE. A MANOVA (p < 0.05)
      demonstrated a significant effect of education over most of the BDAE subtests.
      Females outperformed males on some reading and writing subtests. SES had an
      effect over body part identification and naming. Significant differences were
      observed between younger and middle age groups in confrontation naming, oral and
      word picture reading. The older group scored significantly lower than the younger
      group in serial writing and sentences to dictation. No differences were observed
      between the older and the middle groups. Only oral spelling was affected by the
      type of occupation but a significant interaction of occupation and level of
      education was found. CONCLUSIONS: Language tests are influenced by demographic
      variables, particularly education. Normal variability on the BDAE should be
      considered when dealing with clinical populations.

PMID- 9658470
TI  - [Value of cranial MRI in the follow-up of dural sinus thrombosis].
AB  - INTRODUCTION: At the present time it is well established that cranial magnetic
      resonance (MR) is the imaging technique of choice for diagnosis of thrombosis of
      the dural sinuses. However, few studies have been done to evaluate its role in
      follow-up in this cerebrovascular disorder. OBJECTIVE: To assess the alterations
      in resonance signal in follow-up of patients with thrombosis of the dural sinuses
      and the clinical correlation of this. MATERIAL AND METHODS: We reviewed the
      clinical histories of 12 patients diagnosed on cranial MR as having thrombosis of
      the dural sinuses; 8 cases were also seen again six months later. The cranial MR
      study was done using a 1.5 or 1.0 T superconductive apparatus to do measured spin
      echo sequences (SE) in T1 and T2 in sagittal, transverse and coronal planes. The
      time elapsed between diagnosis on MR and clinical diagnosis was between 24 hours
      and 6 months. RESULTS: All patients had stronger resonance signals in T1 and T2
      indicating a subacute phase of the thrombosis (oxidative conversion of
      deoxyhaemoglobin to methoxyhaemoglobin) and complete absence of blood flow in the
      sinuses. The eight patients seen again after six months were found to be normal
      on neurological. On cranial MR partial recanalization was seen in 5 of these
      (62%). CONCLUSION: Changes in the resonance signal persist for a long time both
      with and without signs of recanalization. This finding does not affect the medium
      term clinical course.

PMID- 9658471
TI  - [Postural hypotension with non-neurogenic triggers in the elderly].
AB  - INTRODUCTION: Orthostatic hypotension (OH) symptoms are the most frequent reason
      for patients to undergo an autonomic examination. The incidence of these symptoms
      is greater in two groups: young people with neurally mediated syncope, and adults
      older than 60 years, all who have normal results in the EKG and EEG test. The
      baroreflex afferents induce a continuous blood pressure adjustment through the
      heart rate variation. There are functional changes with aging which reduce this
      baroreflex sensitivity and therefore the accommodation to the haemodynamic
      requirements is frequently impaired. A number of no neurogenic triggers can be
      implicated in the development of OH symptoms such as electrolytic disorders,
      arrhythmia with low stroke volume and drugs side effects. MATERIAL AND METHODS:
      To study the influence of these factors in the elderly suffering from OH, we
      reviewed patients older than 60 years sent to our laboratory during the last
      three years. In 40 out of 207 cases we found the existence of some of the above
      mentioned factors as possible trigger of the symptoms, since no autonomic
      abnormality was present. After arrhythmia correction, in two cases, and the
      pharmacologic agent suppression, in four more patients, symptoms disappeared and
      no OH was found in a second tilting test. OH is a frequent problem in the elderly
      and requires a careful review of the numerous causes that could contribute to
      develop the symptoms. CONCLUSIONS: To take the proper therapeutic decision, a
      long term monitoring seems to be necessary for the main parameters: blood
      pressure and EKG.

PMID- 9658472
TI  - [Rasmussen syndrome].
AB  - INTRODUCTION: Rasmussen's encephalitis is a neurological disorder probably of
      immunological origin, characterized by intractable epilepsy, neurological
      deterioration and the presence of antibodies against R3 glutamate receptors.
      OBJECTIVE: To present the experience of an Argentinian Paediatric Neurology
      Service during the past 7 years. MATERIAL AND METHODS: We analyzed the clinical
      histories of 12 patients with RS as defined by the diagnostic criteria proposed
      by Hart et al. We evaluated the following parameters: neurological examination,
      neuropsychological assessment, types of crises, age of onset, frequency,
      distribution, electroencephalogram, video EEG, evoked potentials, neuro
      radiological studies; CT and cerebral MR using gadolinium, SPECT, lumbar puncture
      and cerebral biopsy. RESULTS: The crises were of simple partial motor type in 12
      cases, secondarily generalized partial crises in 7 cases, complex partial crises
      in 4 cases and partial and generalized motor states in 8 cases. RESULTS. The
      ictal EEGs during the continuous partial crises showed contralateral focal slow
      activity of the affected side of the body in 30% of cases. The neuro-radiological
      studies (CT and MR) showed signs of cerebral hemiatrophy in all 12 cases, hyper
      intense images in the T2 sequences of the fronto-temporo-parietal regions in 5
      cases, an asymmetric megacisterna magna in 1 case and hypoplasia of the
      cerebellar vermis in another case. CONCLUSIONS: The continuous partial crises
      showed little correlation with the electro-encephalography. Following
      administration of i.v. gammaglobulin there was a transient halt in progression of
      the neurological deterioration and control of the crises in 55% of the cases.
      Surgery continued to be the treatment recommended for control of the epileptic
      crises.

PMID- 9658473
TI  - [Study of the brachial plexus by magnetic resonance].
AB  - OBJECTIVE: Magnetic resonance (MR) is considered to be the best method available
      at present for diagnosis of lesions of the brachial plexus. In this study we
      analyze our experience in patients with pathology of the brachial plexus.
      MATERIAL AND METHODS: Between August 1991 and March 1997 we did magnetic
      resonance studies on 42 patients with pathology of the brachial plexus. Our
      protocols included T1, T2 axial spin-echo sequences with 5 mm cuts and coronal
      echo of a T1-3D gradient with 2 mm cuts, together with a T1 coronal spin-echo,
      with cuts 2 mm in width. RESULTS: The causes found were: traumatic 16 patients
      (38%), pathology of bone 2 (4.7%), 19 tumours (45.2%) with breast cancer being
      commonest, and no obvious aetiology in 5 (11.9%). CONCLUSIONS: MR is the
      technique of choice for study of pathology of the brachial plexus of traumatic or
      tumour origin. In some patients, 11.9% in our series, no aetiology could be
      detected using MR.

PMID- 9658474
TI  - [Topographic distribution of visual evoked potentials in optic neuropathy].
AB  - INTRODUCTION: Digital treatment of electrical signals coming from the central
      nervous system on stimulation of the optic nerve path offers an objective method
      for evaluation of visual evoked potentials (VEP) shown graphically on a cerebral
      map. OBJECTIVE: To evaluate the topographical distribution of VEP in cases of
      optic neuropathy adding this parameter to the usual parameters of latency and
      amplitude. MATERIAL AND METHODS: We studied 35 patients with suspected optic
      neuropathy and normal findings on basic ophthalmological examination, in whom VEP
      and VEP mapping (VEPM) was done. RESULTS: In 26% of the cases there was no
      response for evaluation with the usual VEP recording techniques, whilst in those
      with VEPM this percentage was reduced to 11.5%. In the other cases there was a
      potential with characteristic distribution in the occipital areas and a maximally
      positive dipole posteriorly. CONCLUSION: VEPM is an objective method for
      evaluation of the visual pathway offering better discrimination than the usual
      VEP in more severe cases of neuropathy.

PMID- 9658475
TI  - [Neuroradiology, a specialty among the neurosciences].
AB  - Neuroradiology as a Neuroscience speciality has to keep undoubtedly a narrow
      relationship with the rest of the branches of Neurological Diagnostic, but mainly
      with Clinical Neurology, Neurosurgery and Neuropathology. It is specially
      remarked that cooperation with Neurosurgery has to be very narrow not only in
      diagnostic field as in evaluation of Neuroradiology operation techniques
      (endovascular therapy) as in the field of Stereotaxis and Radiosurgery.

PMID- 9658476
TI  - [Direct communication on the Internet. Uninet: the university link for Integrate
      Telematic Services].
AB  - The importance of Internet as a communication medium is clear due to the amount
      of information it distributes and the high number of potential recipients it has.
      The appearance of virtual user communities (CMV) focuses to information
      classification within subjects of interest for certain groups of people in order
      to facilitate its search and use. The UniNet project of Integrated Telematic
      Services for CMV through, as well as other subprojects, the 'propuesta RedUni'
      encourages the creation of CMV by mean of integration of various computer and
      Internet resources, such as distribution mailing list, web pages, Internet Relay
      Chat (IRC), etc. The current state of IRC in such context is presented and the
      utilities of the known as Scientific-IRC as a professional real time
      communication tool are discussed.

PMID- 9658477
TI  - [Arteriography using helicoidal computerized tomography in the study of complex
      aneurysms of the circle of Willis].
AB  - INTRODUCTION: Computed tomography angiography (CTA) can add information to
      digital subtraction angiography (DSA) in selected cases of aneurysms of the
      circle of Willis. CLINICAL CASES: 1. Patient with progressive visual loss and
      headache. CT and DSA showed an image of partially thrombosed suprasellar
      aneurysm. CTA better defined the relationship between the lesion and regional
      vessels. 2. Woman with subarachnoid hemorrhage (SAH). CTA defined the aneurysmal
      neck and its relationship to the clinoid process. 3. Man with SAH, CT and DSA
      showed an arteriovenous malformation and three arterial aneurysms one of which
      was in a tortuous vessel. CTA confirmed digital angiographic data. CONCLUSION:
      CTA is a new image technique that can either add or confirm DSA findings in
      complex aneurysms of the circle of Willis.

PMID- 9658478
TI  - [Clinico-radiological dissociation in cerebral hemorrhage caused by
      afibrinogenemia].
AB  - INTRODUCTION: Congenital afibrinogenemia is a very rare hereditary anomaly of
      coagulation. Only 150 cases have been published. Clinical manifestation in the
      form of some type of bleeding is similar to that of other congenital
      coagulopathies, although the pattern of presentation is different. Spontaneous
      bleeding is rare, but slight injury, which may be unnoticed, may trigger it off.
      In spite of being a congenital condition, it may be of late onset, as in our
      patient, with bleeding episodes occurring in the second decade of life. CLINICAL
      CASE: We describe a woman who had several episodes of bleeding, two of which were
      intracerebral. The principal feature of this was dissociation between the
      clinical findings and their detection by neuro-imaging. Substitutive therapy led
      to the disappearance of symptoms. CONCLUSION: Cerebral haemorrhage in the
      presence of afibrinogenemia may fail to be detected early on CT. On clinical
      suspicion of bleeding, early substitutive treatment should be started.

PMID- 9658479
TI  - [Progressive aphasia without dementia].
AB  - INTRODUCTION: Slowly progressive aphasia without generalized dementia is
      considered as a degenerative disorder that can be differentiated of others well
      known neurodegenerative disorders. CLINICAL CASE: We present a case report of a
      patient with slowly progressive aphasia, characterized by a progressive anomia
      and without generalized dementia. The patient was evaluated in the last four
      years: a neuropsychological assessment, a neurological exploration and structural
      (MRI) and functional (SPECT) neuroimaging were performed. CONCLUSION: This case
      is interesting on account of a selective implication of the left temporal
      hemisphere is showed in the pathogenesis of this disorder.

PMID- 9658481
TI  - [HIV myelopathy as the presenting symptom of acquired immunodeficiency syndrome].
AB  - INTRODUCTION: Spinal lesions in the acquired immunodeficiency syndrome (AIDS)
      occur in 22% of all neurological complications, although their occurrence as the
      first sign of the disease is very uncommon. First place amongst the myelopathies
      described as associated with HIV is taken by vacuolar myelopathy, followed by the
      myelites. CLINICAL CASE: We studied a 65 year old homosexual man who had
      previously been free of symptoms and signs of HIV infection. He was seen for
      progressive paraparesia which had begun some days previously, followed by altered
      sense of position and of vibration. Complementary tests showed that the patient
      was a carrier of HIV antibodies in high titre (P-24) with a high viral load of
      907 x 1,000 copies RNA/ml. Testing with evoked potentials showed changes
      compatible with involvement of the sensory pathways of the spinal cord. After
      treatment with dexamethasone there was obvious improvement with partial recovery
      of his symptoms. CONCLUSIONS: The neurological condition described was compatible
      with vacuolar type myelopathy due to HIV, appearing in the initial stages of the
      illness and coinciding with a marked increase in the viraemia. Although necropsy
      is necessary for confirmation of the diagnosis, more and more evidence is being
      found on which to base clinical suspicion. We discuss various hypotheses
      regarding possible pathogenic mechanisms arising in these circumstances.

PMID- 9658480
TI  - [Central nervous system infection by free-living amebas: report of 3 Venezuelan
      cases].
AB  - INTRODUCTION: Infection of the Central Nervous System by free living amebas is an
      unusual event, 344 cases have been reported to date. The disease becomes evident
      in two different clinical fashions: Primary Amebic Meningoencephalitis (PAM)
      caused by Naegleria fowleri and Granulomatous Amebic Encephalitis (GAE) induced
      by Spp. of Acanthamoeba and Balamuthia. CLINICAL CASES: The authors report three
      new cases from Venezuela. Case 1. 34 years old man, with a chief complaint of
      general malaise, headache and fever, a diagnosis of common cold was made and the
      patient was treated as such, he did not improve and was admitted to the hospital
      with deterioration of his clinical status; the patient died 10 days after the
      onset of his illness which was determined to be GAE produced by Balamuthia
      mandrillaris. Case 2. 8 years old female admitted to the hospital because of
      fever, headache and generalized seizures of sudden onset; neurocysticercosis was
      diagnosed and following improvement the patient was discharged and readmitted on
      two occasions because of relapse and worsening of her illness, she died 2 months
      after the onset of her disease that was diagnosed by autopsy as GAE due to
      Balamuthia mandrillaris. Case 3. 16 years old male, previously healthy, who
      following immersion in a water tank was admitted to the hospital because of
      meningeal irritation that progressed to coma and death in a 7 day lapse; autopsy
      revealed PAM by Naegleria fowleri. The two cases of GAE due to Balamuthia
      mandrillaris occurred in apparently immunocompetent individuals, contrary to the
      statement that these microorganisms are opportunistic. CONCLUSION: We believe
      that neurological infection by amphizoic amebas is being underdiagnosed, probably
      due to ignorance regarding this pathology or because of a very low autopsy rate
      in most countries.

PMID- 9658482
TI  - [Partial complex status epilepticus: diagnostic difficulties].
AB  - INTRODUCTION AND CLINICAL CASE: We present a case of complex partial non
      convulsive status epilepticus which we think it is very interesting because it
      caused a challenged diagnostic. The patient, a male of eleven years old had
      affective symptoms in episodes. They occurred lasted six to eight hours, once or
      twice a month. The seizures began after a stressfully psychology experience.
      Currently and after of some months of follow-up, the patient is free of symptoms
      and he receives a treatment with valproate acid and vigabatrin. CONCLUSION: We
      also discuss possible precipitating factors, differential diagnosis and
      prognosis.

PMID- 9658483
TI  - [Familial benign partial epilepsy of early infancy].
AB  - INTRODUCTION AND CLINICAL CASES: We present two patients who at the ages of 5 and
      17 months respectively presented with convulsive crises with motor signs, of
      partial onset and secondary generalization, which eventually became normal. Both
      patients had a family history of first degree relatives with similar illnesses
      and are at present-five years later-well and with normal development, school
      achievement and neurological examination findings. The clinical characteristics,
      normal biochemical and neuroimaging investigations and EEG characteristics
      suggest the diagnosis of benign partial epilepsy of early infancy. This syndrome
      is characterized by its appearance during the first year of life, having no known
      etiological factors, with partial crises occurring several times a day and with a
      course leading to remission. Its frequency may be greater than is thought. There
      is a pattern of dominant autosomal inheritance, with a gene recently found on
      chromosome 19. CONCLUSION: We consider that this syndrome should be included in
      the International Classification of Epilepsy and Epileptic Syndromes as benign
      familial idiopathic partial epilepsy.

PMID- 9658484
TI  - [Paraneoplastic cerebellar degeneration with asymmetrical pan-cerebellar
      syndrome].
AB  - INTRODUCTION: Paraneoplasic cerebellar degeneration is seen clinically as a
      pancerebellar condition which is usually symmetrical. Different families of
      tumours are associated with this, particularly (in view of its frequency) oat
      cell pulmonary carcinoma, gynecological tumours and Hodgkin's lymphoma. CLINICAL
      CASE: Signs of cerebellar atrophy were seen on MR and cortical hypoperfusion was
      seen on Single Photon Emission Computerized Tomography (SPECT). We present the
      case of a 76 year old woman who presented with an asymmetrical pancerebellar
      disorder of gradual onset, with positive anti-self antibodies and
      undifferentiated carcinoma of the breast. CONCLUSIONS: Paraneoplasic cerebellar
      degeneration should be suspected in a patient with symmetrical, progressive
      cerebellar disease. The syndrome characteristically starts with a slightly
      uncoordinated gait. This progresses over a period of weeks or months to an ataxic
      gait with incoordination of the limbs, dysarthria and frequently nystagmus with
      oscilloscopy. No satisfactory treatment has been found for DCP in spite of trials
      with vitamins, corticosteroids, plasmapheresis and immunoglobulin infusion.
      Slight improvement may be seen after treatment of the primary tumour.

PMID- 9658485
TI  - [Acute phenytoin poisoning secondary to an interaction with ticlopidine].
AB  - INTRODUCTION: Ticlopidine and phenytoin are two drugs which are widely used in
      everyday clinical practice, the first as a platelet anti-aggregant and the second
      as an anti-epileptic agent. Their association is not uncommon, since there is a
      high incidence of epileptic crises of vascular origin in adults. CLINICAL CASE:
      We present the case of a 77 year old man who had been treated for twenty years
      with phenytoin for partial crises secondary to a left frontal hematoma. He then
      followed treatment with ticlopidine for a femoropopliteal bypass, and the dose
      was later increased because of a vertebro-basilar ictus. On both occasions he
      presented with ataxia, dysarthria and nausea due to phenytoin intoxication. The
      blood levels of this drug were above the therapeutic level. The symptoms
      disappeared and the patient returned to normal after reduction of the dose of
      phenytoin and suspending treatment with ticlopidine. DISCUSSION: The mechanism of
      action of ticlopidine at cytochrome P450 level, inhibiting the metabolic
      clearance of phenytoin, was responsible for this interaction. We have found only
      three other cases of interaction between these drugs in the literature, and ours
      is the first to be published in Spain. CONCLUSION: We emphasize the importance of
      checking plasma phenytoin levels when starting treatment with ticlopidine, since
      it may be necessary to reduce the dose of phenytoin.

PMID- 9658486
TI  - [Polyneuropathy caused by vitamin B12 deficiency secondary to chronic atrophic
      gastritis and giardiasis].
AB  - INTRODUCTION: In chronic atrophic gastritis atrophy of the stomach glands leads
      to intrinsic factor deficit, with consequent failure to absorb vitamin B12 and
      gastric achylia, which predisposes to Giardia infection which in itself leads to
      depletion of vitamin B12. We describe the case of a patient with peripheral and
      central nervous system pathology due to lack of vitamin B12 secondary to the
      combined effect of these two disorders. CLINICAL CASE: A 54 year old woman
      consulted us for paraesthesia and weakness of the legs which had been progressive
      for the previous two years. She presented with tactile hypoaesthesia,
      hypoparaesthesia, distal hyperreflexia and dysymmetry of the legs, ataxic-spastic
      gait and a positive Romberg sign. The investigations carried out showed the serum
      vitamin B12 level to be 3 pg/ml (N: 180-900), hemoglobin 13 g/dl and MCV 111 fl
      with MCHC 348/dl; neurophysiological studies: compatible with demyelinating motor
      polyneuropathy. Schilling test: deficit of absorption of vitamin B12 which was
      corrected on administration of intrinsic factor; gastroscopy; atrophic gastritis
      which confirmed the morbid anatomy findings. There was also flora containing
      Helicobacter and massive Giardia infection. Replacement and antibiotic therapy
      was followed by complete remission of the clinical picture. CONCLUSION: We
      emphasize the excellent clinical response to treatment in spite of the time
      elapsed since onset of symptoms.

PMID- 9658487
TI  - [Dystrophinopathies, congenital muscular dystrophy, limb-girdle dystrophies:
      updated classification].
AB  - OBJECTIVES: To review the up-dated classification of limb girdle muscular
      dystrophies (LGMDs) in relation to the defective protein and the genetic
      abnormality. To explain how these proteins are related to dystrophin and to the
      proteins of the extracellular matrix. To show that an accurate diagnosis is
      necessary and that it can be adequately made in neuromuscular pathology
      laboratories. DEVELOPMENT: We present a study of the different types of LGMDs,
      dystrophinopathies and congenital muscular dystrophy. We emphasize the recent
      events which concluded in the identification of these disorders, the genetic
      alteration, the defective proteins and, briefly, the clinical features.
      CONCLUSIONS: The recent identification of numerous skeletal muscle proteins and
      of the codifying genes made possible a new classification of a large group of
      muscular dystrophies. The possibility to study these proteins on the muscle
      biopsy with immunohistochemistry and Western blot techniques indicates the need
      of an accurate diagnosis in specialized neuromuscular laboratories. Since there
      is a great number of genes discovered and of mutations within the same gene, and
      the clinical picture of different diseases can be similar, a previous study of
      the protein is advisable as a guide for a further genetic study.

PMID- 9658488
TI  - [Brain-derived growth factor: current aspects].
AB  - INTRODUCTION: The neurotrophins are a family of proteins which are closely
      related structurally and functionally and include nerve growth factor (NGF),
      brain derived nerve factor (BDNF) and neurotrophin-3 (NT-3), neurotrophin-4/5 (NT
      4/5) and more recently neurotrophin-6 (NT-6). BDNF is one of the most important
      endogenous proteins for control of survival, growth and differentiation of
      certain neurone populations both in the peripheral and central nervous systems.
      DEVELOPMENT: The ARNmt of the BDNF is found in nearly all regions of the brain.
      The highest levels are those of the hippocampus and cerebral cortex. The large
      number of effects attributed to BDNF are probably due to the union of this
      protein to its specific receptor on the cell surface, which leads to the
      formation of a complex which enables transmission of the signal caused by
      activation of the specific neurone pathway. Since discovery, BDNF has been
      detected and/or measured by different methods from biological assay to the
      application of molecular biology techniques. These methods have permitted
      analysis of the biochemical characteristics of this factor and its behaviour in
      different tissues. CONCLUSIONS: In this paper we review the most relevant aspects
      of distribution, biological actions of BDNF on different neurone populations, its
      clinical usefulness in neurological disorders, routes of administration and side
      effects.

PMID- 9658489
TI  - [Nerve growth factor and diabetic neuropathy].
AB  - INTRODUCTION: The progress made by contemporary neurobiology opens new horizons
      both for study and for treatment of disorders of the nervous system. At the
      present time we are in the age of growth factors. These are molecules which
      affect survival, development and the normal functioning of cell populations.
      DEVELOPMENT: One of the most widely studied growth factors is nervous growth
      factor (NGF) which is necessary for normal life of various types of neurones,
      including sensory nerves and nerves derived from the neural crests. Diabetic
      neuropathy, worldwide a major neurological disorder, is primarily characterized
      by involvement of the fine fibres for temperature and pain perception and also by
      a variety of autonomic disorders. The great dependence of sensory and sympathetic
      nerves on NGF, the quantity of results which show alterations in the levels of
      neurotrophic factors in diabetic neuropathy (DN), and the encouraging
      experimental and clinical results of using NGF as a new alternative to treatment
      with DN, were the basic reasons which led us to do this study. CONCLUSIONS: We
      started by considering neurotrophic factors, especially NGF and its connection
      with DN disorders and its clinical applications, we made a summary of the main
      findings in this field to date.

PMID- 9658490
TI  - [A new formulation of death: definition, criteria and diagnostic tests].
AB  - OBJECTIVE: To present a new formulation of human death based on neurological
      considerations. DEVELOPMENT: One of the reasons there is still controversy over a
      new formulation of human death which is acceptable to society, is that many
      authors do not suitably integrate three fundamental aspects which should be
      included in such a formulation: definition, criteria and diagnostic tests. We
      review the physiopathological mechanisms for generation of consciousness and
      discuss the three fundamental criteria presented by different authors in recent
      decades: the whole encephalum, brainstem death and neocortical criteria. We
      conclude that there are major contradictions in the three criteria with regard to
      satisfactory integration of the elements, definition, criteria and diagnostic
      tests. We therefore present a new formulation of human death. DEFINITION:
      irreversible loss of consciousness, since this gives the essential human
      attributes, and is the most integrating function of the organism. CRITERIA:
      cortico-subcortical connections for the generation of both components of
      consciousness (capacity and content). DIAGNOSTIC TESTS: no waking response to
      stimuli (capacity), no cognitive nor affective functions (content). CONCLUSIONS:
      We present a new formulation of human death on a neurological basis which permits
      satisfactory integration of the three fundamental elements, definition, criteria
      and diagnostic tests, and so offers a suitable starting point from which man may
      start to understand death.

PMID- 9658491
TI  - [A complete and precise reformulation of human death].
AB  - INTRODUCTION: Today, a very active debate exists about the concept and
      determination of death. The lack of both an integrating rationale and a
      consistent and precise formulation to approach such a fundamental issue has been
      notable. However, a contribution regarding both aspects is indispensable to
      overcome inconsistencies affecting current death concepts. DEVELOPMENT: It is
      argued in this article why a sufficiently defined 'consciousness-organism-as-a
      whole' system and its critical metafunction determines the neurological standard
      for a complete and precise reformulation of human death. This metafunction cannot
      be reduced to any of the particular functions of the system. It characterizes the
      highest hierarchical level of qualitative organization in the human organism. It
      defines the criticality of the system and the ontological level pertinent to the
      definition of death. Human death is 'both the irreversible loss of consciousness
      (considering its three anatomical and physiological components), and, inherently
      and inseparably, the loss of the capacity of the organism to function as a
      whole'. CONCLUSIONS: It is argued why the rationale supporting this definition
      overcomes the problems posed by either currently accepted conceptions or by those
      competing to gain acceptance. Some of the implications of this re-approach in the
      intersection of neurology with other disciplines are considered.

PMID- 9658493
TI  - ["El Informe Medico-Moral de la Penosissima y Rigorosa Enfermedad de la Epilepsi"
      (1763) by the Spaniard Pedro de Horta, the 1st American treatise on epilepsy].
AB  - In 1763 Pedro de Horta was requested by the prioress of the convent of San
      Geronimo in Puebla de los Angeles to draw up a report to establish whether the
      epidemic of queer turns, violent shaking or epilepsy which affected the novices
      was caused by the Devil or was due to natural causes. Pedro de Horta, a doctor
      qualified in Mexico, methodically and thoroughly prepared an extensive
      monographic treatise on the illness which included all that was known at the
      time. The report showed the fierce debates provoked by the subject of epilepsy in
      the eighteenth century regarding whether it was of natural or supernatural
      origin. It also contained detailed accounts of the episodes, their causes and
      treatment. The Spaniard Pedro de Horta should be justly recognized as the first
      American epileptologist.

PMID- 9658492
TI  - [Medical treatment of Alzheimer's disease].
AB  - OBJECTIVE: To review the drugs commercially available at present and in the near
      future in relation to the evolution of Alzheimer disease, bearing in mind the
      possible psychiatric disorders which may be associated with the disease.
      DEVELOPMENT: The therapeutic approach is planned according to the different
      phases of the disease. In the preclinical phase, anti-inflammatory drugs and
      estrogens in post-menopausal women have been effective. In the initial phase
      current recognition therapy is directed basically towards correcting the break
      down of acetylcholine (tacrine, donepezil, SB202026, SDZ ENA 713). For depressive
      symptoms serotonin levels are corrected using selective inhibitors of serotonin
      uptake. CONCLUSIONS: Drug treatment should be considered with the association of
      drugs which activate the malfunctioning circuits and/or pathways. It would also
      be useful to design clinical studies using pharmacological combinations of
      cholinergic agonists, estrogens, anti-inflammatory drugs, seligiline and/or new
      anti-cholinesterase drugs amongst others.

PMID- 9658494
TI  - [Magical thinking and epilepsy in traditional indigenous medicine].
AB  - INTRODUCTION: Witchcraft with regard to epilepsy in ancestral indigenous cultures
      has been modified by the presence of white doctors so that traditional and
      scientific-western treatments coexist. OBJECTIVE: To analyze traditional anti
      epileptic treatment and the basis of the relevant magic in diverse indigenous
      cultures in Central Africa and in Central and South America. MATERIAL AND
      METHODS: Transcultural analysis of the Bassa, Fufulve and Bambilike tribes (Log
      bikoy, Camerun), Wangoni (Songea, Tanzania), Guarani (Paraguay) and Maya Tzeltal
      (Chiapas). RESULTS: In traditional Africa epilepsy is linked to the evil eye. In
      the Wangoni tribe the curative ritual requires complete shaving of the entire
      body using glass, or banishment of the person causing the evil influence. In the
      Bassa and Bambilike, burns are a common complication and epilepsy is known as the
      disease of people with burns. In Meso-american culture epilepsy is caused by some
      abuse suffered by the animal soul which accompanies the person involved,
      following a battle between the naguales or spirits who serve the forces of Good
      and Evil. Traditional indigenous medicine employs herbal remedies, rituals,
      spiritual cures or combinations of all these. More than 80% of the epileptic
      patients of the Third World use only these remedies. CONCLUSION: The mythical
      concept of the disease is the basis for interpretation of epilepsy in traditional
      indigenous cultures. The psychological benefit obtained from the traditional
      therapeutic model has made this necessary and complementary to western-style
      treatment.

PMID- 9658495
TI  - [Quality of life of the pediatric epileptic patient].

PMID- 9658496
TI  - [Acute disseminated bulbospinal encephalomyelitis in an adult patient].

PMID- 9658497
TI  - [Neurocysticercosis and convulsive crises].

PMID- 9658498
TI  - [The concept of "person" and its neurological foundations].

PMID- 9658499
TI  - [Neurology and the concept of health].

PMID- 9658500
TI  - [William G. Lennox and the International League against Epilepsy: sketch of a
      life and an opus].

PMID- 9658501
TI  - [Guillain-Barre and varicella infection].

PMID- 9658502
TI  - [Transitory comatose situation secondary to an infarction of the posterior
      circulation, reversed by naloxone?].

PMID- 9658503
TI  - [Prevalence of amyotrophic lateral sclerosis on the island of La Palma, Spain].

PMID- 9658504
TI  - Health promotion in school age children.
AB  - Disadvantage in school age affects health during the remaining part of life.
      Health promotion might alleviate this situation. It is reasonable to focus on
      mental health, since this is the leading cause of disability adjusted life years
      lost in this age group and to focus on the school, since this is the most
      important setting. Co-operation between the public health and the educational
      sector is rational, yet complicated by different perspectives on knowledge and
      technology used in these two sectors. It is, however, possible to carry through a
      dialogue. Then, the public health representatives have to clarify current
      scientific knowledge on health promotive characteristics of the school. Such
      characteristics are, enhanced health control at school, aged mixed ability
      grouping, class sizes of 15-20 students, a task oriented school culture and
      employment of skills training programmes, e.g. for tobacco deterrence.

PMID- 9658505
TI  - Rehabilitation research under fire.
AB  - Catastrophes in the health area are frequent. A template for conduct and
      reporting of research in disaster responses has recently been published. The WHO
      Rehabilitation of War Victims Project basically followed these principles in
      former Yugoslavia to estimate defined needs, prioritise and evaluate methods
      used. Around 30% of war victims reported to be wounded were found to be in need
      of physical rehabilitation. Priority was given to the 5% with severe disabilities
      caused by amputations, spinal cord injuries and traumatic brain injuries. Most of
      the infrastructure was destroyed and WHO supported a community based
      rehabilitation approach (CBR). Evaluating this type of service delivery became
      extremely difficult under present circumstances. Waves of refugees rolled both
      within the republics and over the borders demonstrating both the needs and
      problems listed in the template referred to. The CBR service delivery worked out
      satisfactorily with high patient satisfaction. Limited medical training greatly
      improved the situation for the personnel. Even in a disaster situation research
      is needed for proper decision-making and to gain experiences for future aid.

PMID- 9658506
TI  - Social support, social disability and their role as predictors of depression
      among patients with congestive heart failure.
AB  - The purpose of this study was to assess the effect of social support variables,
      personality, clinical variables (New York Heart Associations classification), and
      social disability upon depression. The sample consisted of 119 clinically stable
      patients (34 females, 85 males) with symptomatic heart failure, recruited from an
      outpatient hospital practice. The patients underwent a brief physical examination
      and completed a set of questionnaires. Descriptive statistics were used to
      characterise the patients' informal functional network. The analysis revealed
      that the intimate social network support (spouses) and primary social network
      support (close family) were rated as most supportive. Results from the path
      analysis showed that social disability was explained by the two personality
      factors, neuroticism and extraversion, and by the severity of disease (NYHA). No
      significant effects of the social support variables upon social disability were
      detected. Moreover, path-analyses showed that poor intimate network support,
      social disability and neuroticism were significantly positively associated with
      depression.

PMID- 9658507
TI  - Work disability and health-affecting psychosocial problems among patients in
      general practice.
AB  - Psychosocial problems are often ignored among patients in general practice. By
      identifying high risk groups this situation could possibly be altered. This study
      aimed to explore if patients in general practice perceiving themselves as work
      disabled by at least 50% more often have health-affecting psychosocial problems
      than those not work-disabled. In a geographically defined population, 1,058
      consecutive adult patients consulting 89 general practitioners were approached
      during one regular working day in March 1995. They completed a questionnaire at
      home, returning it directly to the department of general practice. Male patients
      considered themselves work-disabled more often than female patients. All
      psychosocial problems except having a demanding caregiving task were more common
      among the work-disabled. The doctors should bear in mind that work-disabled
      patients more often than other patients have concomitant health-affecting
      psychosocial problems. Granting long-term sick leave or a disability pension may
      not be the only management needed.

PMID- 9658508
TI  - Disability pension in Malmohus county: aspects on long-term financial effects.
AB  - The purpose of this study was to estimate the financial costs of disability
      pension in order to compare the financial burden and the numerical distribution
      of disability pension by main diagnostic groups. During three months all new
      disability pensions (n = 944) granted in Malmohus county were registered. During
      a follow-up of approximately two and a half years, 40 subjects died and 15
      pensions expired. The predominating diagnoses were musculoskeletal diseases,
      mental disorders including alcohol dependence, cardiovascular and neurological
      diseases. To analyse whether these proportions changed when the extent of the
      pension, age at pension and the retirement allowance were considered, the present
      value of the total retirement allowances was calculated. The ranking of the four
      predominating diagnosis categories was not affected by the extent of the pension
      or the age at which the pension was granted. Thus, musculoskeletal diseases still
      predominated, although the proportion decreased. Among unemployed subjects,
      mental disorders made the largest contribution to the total expenditure. The
      results gained may be used in further research where alternatives to disability
      pension for different groups of patients and/or diagnoses are investigated.

PMID- 9658509
TI  - Comparison of stress, job satisfaction, perception of control, and health among
      district nurses in Stockholm and prewar Zagreb.
AB  - The increasing number of studies of stress among nurses in the last two decades
      have mainly dealt with nurses in hospitals. A few studies have included community
      based nurses. However, no comparative studies of district nurses in different
      countries have been published. We have conducted a study to identify sources of
      stress, job satisfaction, perceived demands, control and health among district
      nurses (DNs) in Zagreb (Croatia) and Stockholm (Sweden), working in a polyvalent
      health care organization. Data were obtained regarding altogether 305 district
      nurses by means of self-administered questionnaires using identical methods and
      items, with response rates between 88% and 95%. In general, district nurses
      reported high levels of job-related stress, satisfaction and control.
      Organizational sources of stress, such as ongoing changes in the primary care
      organization, and reorganization of tasks, were of importance for the district
      nurses in Stockholm. They reported also more job satisfaction and commitment than
      the district nurses in Zagreb. The district nurses in Zagreb had significantly
      higher level of "lack of resources". They displayed significantly higher scores
      of psychological demands but also a greater feeling of control than the district
      nurses in Stockholm. Significant differences were also found between the groups
      in ranking of self-reported stressors. Thus results show that differences in work
      organization and in essential resources have a substantial impact of perceived
      stress, job satisfaction, and on the generality both of single association and on
      the applications of models.

PMID- 9658510
TI  - Children's residential exposure to environmental tobacco smoke varies greatly
      between the Nordic countries.
AB  - OBJECTIVE: To assess similarities and differences in the Nordic countries
      regarding ETS (environmental tobacco smoke) exposure in young children. DESIGN: A
      population-based cross-sectional study comprising a randomly selected sample of
      5,500 households which included a child born in 1992. Data were collected using a
      mailed anonymous questionnaire. RESULTS: While the prevalence of household
      smoking was similar in all countries, there was a great difference between the
      countries with regard to child ETS exposure. Finnish parents were more likely
      than all other Nordic parents to protect their children from ETS and the
      situation was worst in Denmark and Iceland, where almost half of all households,
      and nine out of ten households containing daily smokers, exposed their children.
      Approximately eight out of ten current and former smokers in all countries stated
      that they had made efforts to change their smoking habits because of their
      children.

PMID- 9658511
TI  - Social functioning of elderly coronary heart disease patients.

PMID- 9658512
TI  - Indices of need and social deprivation for primary health care.
AB  - This study aimed to examine two indices of need, the underprivileged area (UPA)
      score and a Swedish Care Need Index (CNI, in Swedish vardbehovsindex) with
      weightings from British and Swedish GPs respectively, and an index of material
      deprivation, Townsend score at SAMS (Small Area Market Statistics) level and at
      municipality level for the whole of Sweden. One third of primary health care
      physicians from the whole of Sweden received a questionnaire about their
      workload. CNI, UPA and Townsend scores were calculated using information from the
      Swedish census of 1990 and the registers of unemployment and migration for 1992.
      The Swedish GPs weighted some of the variables quite differently from the GPs in
      the UK. This may be important, especially at the SAMS level. The GPs in both
      countries considered that older people living alone contributed most to their
      workload. However, in Sweden the physicians ranked foreign-born people high
      compared with the English doctors, and in England the GPs ranked children under
      five years much higher than the doctors in Sweden. The correlation between the
      scores was high.

PMID- 9658513
TI  - Quality of palliative care: why nurses are more valued than doctors?

PMID- 9658514
TI  - How to measure sickness absence? Literature review and suggestion of five basic
      measures.
AB  - OBJECTIVE: To examine different sick-leave measures used in sickness absence
      research, and to suggest a systematic way of assessing sickness absence. METHODS:
      A review and analysis of five major studies on sick-leave performed 1983-1988
      with an epidemiological approach. RESULTS: Terminology and measures used varied
      in the different studies reviewed. The choice of a certain measure was seldom
      discussed in relation to the aim of the study. Based on the review five measures
      are suggested: frequency, length, incidence rate, cumulative incidence and
      duration. The definition of incidence rate is new and is a measure useful in
      studies of recurrent events within epidemiology. CONCLUSIONS: We have reviewed
      sick-leave measures previously used in the literature and suggested five basic
      measures for assessing sick-leave.

PMID- 9658515
TI  - Examining what self-rated health question is understood to mean by respondents.
AB  - The aim of this methodological study is to examine what self-rated health is
      understood to mean by survey respondents. The data are derived from semi
      structured (re-)interviews with 42 middle-aged participants of the 1994 Finnish
      Survey on Living Conditions. When the respondents are asked to describe their
      present health, the results show concrete, contextual, and partly contradictory
      conceptions of "health". Health is presented primarily as absence of ill-health,
      but also connected to personal experience and life situation, and as a result of
      action. Second, when assessing self-rated health all respondents base their
      assessments on ill-health, modified by the severity, duration and restrictions
      posed by ill-health. Further analysis shows that some respondents base their
      assessments also on fitness and health behaviour. The results suggest that in
      addition to the medical model of health, adopting health promotion messages and
      "healthy" lifestyles are important factors contributing to health assessments.

PMID- 9658516
TI  - Response rate according to title and length of questionnaire.
AB  - The purpose of this study was to investigate how response rates to a postal
      questionnaire are affected by title and length of the survey instrument. Five
      questionnaires, which differed according to title and length, were designed. Each
      questionnaire was mailed to a random sample of one thousand Norwegian women aged,
      35-49 years. A total of 3,106 questionnaires were returned (62.1%). The highest
      response rate (70.2%) was achieved by a two-page questionnaire entitled "Women
      and Cancer". An otherwise identical questionnaire entitled "Oral Contraceptives
      and Cancer" had a response rate of 60.7%. Questionnaires entitled "Women and
      Cancer" with a length of four and six pages had a response rate of 62.8% and
      63.3%, respectively. The four page questionnaire entitled "Women, Lifestyle and
      Health" had the lowest response rate of 57.1%. This study shows that in a general
      population of Norwegian women the title of a postal questionnaire influences the
      response rate. The results indicate that although the shortest questionnaire had
      the highest response rate, the most extensive survey instrument did not have the
      lowest response rate. The distribution of risk factors for breast cancer did not
      vary according to response rate or design of questionnaire. The overall findings
      of this study suggest that the benefits from the increased information obtained
      from extensive postal questionnaires out-weighs a potential non-response bias due
      to a somewhat lower response rate.

PMID- 9658517
TI  - [Value and limits of conventional mediastinoscopy in preoperative evaluation of
      primary bronchial cancer].
AB  - PURPOSE OF THE STUDY: Retrospective evaluation of conventional mediastinoscopy in
      the preoperative staging of primary lung cancer. METHODS: Between 1978 and March
      1997, 117 consecutive patients underwent conventional mediastinoscopy in the
      preoperative staging of primary lung cancer, after imaging had shown mediastinal
      lymph nodes larger than 1.5 cm. RESULTS: In 8 instances no material was found at
      mediastinoscopy, in 38 the lymph nodes showed no tumorous infiltration, and in 71
      the lymph nodes were metastatic. 48 patients underwent thoracotomy in the same
      stage, with resection achieved in 41. Contraindications for thoracotomy (in 69)
      were N2 (45) or N3 (11) disease adn/or small cell lung cancer (18). Mediastinal
      lymphadenectomy was performed in 26 of the 41 patients who underwent lung
      resection; half of those with negative nodes at mediastinoscopy had in fact N2
      disease, with involvement of 2 areas of more in half. There were no deaths due to
      mediastinoscopy but 4 complications. CONCLUSIONS: A favorable mediastinoscopy is
      not synonymous with resectable disease, nor does it exclude N2 disease; it does
      however serve to avoid unnecessary thoracotomies in more than half of cases.

PMID- 9658518
TI  - [Is infra-inguinal venous bypass less successful in the woman?].
AB  - In the present study the influence of gender in peripheral arterial
      reconstructions was evaluated. Between 1986 and 1990 we performed 173
      infrainguinal vein bypass procedures in 117 men and 56 women. All procedures were
      carried out for chronic critical leg ischaemia. Bypasses in men were femoral to
      popliteal in 68%, and femoral to infragenicular in 32% in cases. The
      corresponding values in women were 52% and 48%. Perioperative 30-day mortality
      was 2% in men and 2% in women. Long-term survival at 5 years was 50% in men and
      44% in women. Life-table primary 5-year patency rates were 81% for men and 74%
      for women. Limb salvage results at 5 years were 87% for men and 84% for women.
      The results indicate that in our experience with autogenous vein longterm graft
      patency and limb salvage results in women are identical to those obtained in men.
      Infrainguinal arterial reconstruction can be performed in women with mortality
      rates similar to those of men.

PMID- 9658519
TI  - [Paraneoplastic cerebellar degeneration (PCD) with anti-Yo antibodies in ovarian
      carcinoma].
AB  - We report the case of 71-year old Caucasian woman with ovarian cancer, who
      developed paraneoplastic cerebellar degeneration (PCD). Pathognomonical anti Yo
      antibodies could be identified in serum specimens. We describe the history and
      clinical presentation and summarise the disease.

PMID- 9658520
TI  - [Pro or contra Papanicolaou cytologic smear every 3 years].
AB  - OBJECTIVE: To analyse the possibility of three-yearly screening for cervical
      cancer after two consecutive normal annual smears. METHOD: Review of the
      literature. RESULTS: In Switzerland 78% of women are screened spontaneously for
      cervical cancer. For 70% of this group the last smear was less than 18 months
      before. In other European countries or in North America programmed screening is
      every 3 or even 5 years. A lowered mortality rate is observed depending on the
      interval between screening. The benefit is only 2.7% between 3-yearly (90.8%) and
      yearly smears (93.5%). Finding an oncogenic HPV [16, 18, 31, 45] whilst
      investigating low grade cervical intraepithelial neoplasia (CIN1) is associated
      with a 17% risk of conversion into high grade cervical intraepithelial neoplasia
      (CIN3) within 3 years. CONCLUSION: In Switzerland the conditions for screening on
      a 3-yearly basis are not fulfilled. We recommend an interval of only 2 years
      after 2 normal annual smears.

PMID- 9658521
TI  - [Unexpected cause of abdominal pain].

PMID- 9658522
TI  - [Surgery of rectal carcinoma: 1997 status assessment].

PMID- 9658523
TI  - Anatomic basis of Tonnis' triple pelvic osteotomy for acetabular dysplasia.
AB  - Dysplasia of the hip in adults can be treated by a pelvic osteotomy. In order to
      assess pelvic anatomy in relation to surgical approach and osteotomy sites, 12
      cadaver hips were studied. A triple pelvic osteotomy as described by Tonnis [6]
      through ilium, pubis and ischium was performed, followed by an intrapelvic and
      anterior and posterior dissection of the hip. At the ischium, the pudendal and
      inferior gluteal neurovascular bundles are most at risk medially and proximally
      respectively. Much less in danger is the sciatic n. as it runs 1 to 3 cm lateral
      to the osteotomy site. At the pubis osteotomy the femoral v. lies close on the
      bone and is prone to damage. The artery lies further off the bone. The ilium
      osteotomy starts just proximal to the anterior inferior iliac spine and exits
      posteriorly at the sciatic notch. Here the sciatic n. and the superior gluteal
      neurovascular bundle may be damaged. The practical surgical implications of these
      three osteotomies are discussed, especially with respect to the requirement of
      meticulous subperiostal dissection and accurate placement of retractors.

PMID- 9658524
TI  - Anatomic bases of tongue flaps.
AB  - The morphological structure of the lingual a. was studied in 50 dissected and 14
      vascular cast specimens. The course of this artery is divided into 4 segments:
      the original segment, the segment within hyoglossus, the ascending and the
      horizontal segments of the deep lingual a. The root of the tongue is supplied by
      2 to 3 root branches of the lingual a., the ascending palatine a. and the
      tonsillar a. The body of the tongue is nourished on averaged by 25 arterial
      branches from the deep lingual a. The ventral surface of the tongue, as well as
      the sublingual gland and the floor of the mouth, is supplied by the sublingual a.
      The termination of the lingual a. The termination of the lingual a. anastomoses
      with the submental branch of the facial a. to form the lingual frenal a. Except
      for a submucous arterial network on the dorsum of the tongue, all blood vessels
      are separated completely by the lingual septum, through which arterial
      anastomoses (2.0 mm in diameter) can be found occasionally.

PMID- 9658525
TI  - Morphologic studies of the venous drainage of the tongue.
AB  - The aim of this work was to study the role of the venous drainage of the tongue
      in tongue inspection in traditional Chinese medicine and tongue-flap surgery.
      Thirty-two adult cadavers were observed, including 7 venous corrosivecast
      specimens. The decreasing order of venous drainage of the tongue, based on the
      diameter of the vein and size of its drainage area, was the accompanying v. of
      the hypoglossal n., the epiglottic valleculate v., the accompanying v. of the
      lingual n., the lingual root v. and the accompanying v. of the lingual a. The
      veins constituting the picture of the tongue seen in sublingual collateral
      inspection were the companion vv. of the hypoglossal and lingual nn. The pedicle
      of a tongue flap must maintain efficient venous drainage canal.

PMID- 9658526
TI  - Anatomic basis of chronic perineal pain: role of the pudendal nerve.
AB  - Our anatomic findings have led us to define conflictual relations that may be
      encountered in their course by the pudendal n. and its branches. Starting from
      the clinical study of a group of patients suffering from chronic perineal pain in
      the seated position, we have defined, beginning with the cadaver, three possible
      conflictual settings: in the constriction between the sacrotuberal and
      sacrospinal ligaments; in the pudendal canal of Alcock; and during the straddling
      of the falciform process of the sacro-tuberal ligament by the pudendal n. and its
      branches. Consequently, considering so-called idiopathic perineal pain as an
      entrapment syndrome, the clinical and neurophysiologic arguments and infiltration
      tests have led us to define a surgical strategy which has currently given 70% of
      good results in 170 operated patients. Earlier diagnosis should improve on this.

PMID- 9658527
TI  - Anatomic study of the umbilical vein and ductus venosus in human fetuses:
      ultrasound application in prenatal examination of left congenital diaphragmatic
      hernia.
AB  - For clinicians it is very difficult to evaluate the prognosis of a left
      congenital diaphragmatic hernia (CDH) at prenatal ultrasound examination.
      Surgical studies show that the presence of a large part of the liver in the chest
      is a criterion of poor prognosis. However, ultra-sonography encounters some
      difficulties in determining the precise position of the liver in the thoracic
      cavity. The aim of this anatomic study was to define the relationship between the
      position of the liver and the path of the ductus venosus and of the umbilical v.,
      which are easily recognizable at prenatal sonography. Twenty dead fetuses were
      used for the study (12 with a left CDH and 8 without). All fetuses underwent
      radiographic assessment, anatomic dissection and cross-sectional study. The angle
      between the umbilical v. and the ductus venosus in different planes was measured.
      The more the liver was in the thorax, the greater was the angle between the
      ductus venosus and the sagittal plane, and the less the angle between the ductus
      venosus and the umbilical v. These angles can be easily measured by prenatal
      ultrasound examination of the fetus. Our findings suggest that it is now possible
      to offer the clinician a new and reliable way to determine the prognosis of a
      left CDH before birth.

PMID- 9658528
TI  - Morphometric evaluation of the sacral dorsal root ganglia. A cadaveric study.
AB  - An anatomic study of the sacral dorsal root ganglia (DRG) was performed to
      determine the location and dimensions of the S1-4 DRGs and to correlate this
      information to sacral nerve root ganglion lesions. S1 DRGs were located in the
      intraforaminal region in 55-60% and in the intracanalar region in 40-45%. S2 DRGs
      were in the intraforaminal region in 15-50% and in the intracanalar region in 50
      85%. All the S3 and S4 DRGs were located in the intracanalar region. None of the
      sacral DRGs was located in the extraforaminal region. The intraforaminal position
      of the S1 and S2 ganglia renders them vulnerable to compression caused by sacral
      fractures involving the sacral foramina because of the little space available for
      these ganglia in the foraminal region. The S1 DRG, with its its relatively larger
      dimensions and its intracanalar position relative to the other sacral DRGs, may
      be susceptible to compression by the L5-S1 disk herniation. Its intraforaminal
      position may predispose it to injury during S1 or S2 pedicle screw placement.

PMID- 9658529
TI  - Intracranial course and relations of the hypoglossal nerve. An anatomic study.
AB  - This anatomic study describes the course and intracranial relations of the
      hypoglossal n. in 32 cadavers. The rootlets of the nerve emerged as a fan-shaped
      distribution (23.44%) or in two bundles (76.56%) and converged towards the
      hypoglossal canal in the subarachnoid space before piercing the duramater. In
      76.57% of cases the rootlets pierced the dura mater in two separate apertures,
      less commonly through the same aperture (21.87%), and in rare cases through three
      individual apertures, as in one of our cases. The distance between the two
      apertures varied from 0.6 mm to 8.7 mm. Commonly, the two bundles converged
      together and left the skull through one foramen in the skull. However, in some
      cases (28.12%), the hypoglossal canal was divided in two by a small bony spicule.
      In 23.45% of cases the initial course of the posterior inferior cerebellar a.
      (PICA) passed between the two bundles of the hypoglossal n. before ascending
      towards the lateral border of the fourth ventricle.

PMID- 9658530
TI  - Technique for injection of the lumbar vertebral venous plexuses employed in
      anatomic, computed tomography and magnetic resonance imaging studies.
AB  - The aim of this study was to develop a technique for injection of the vertebral
      venous plexuses allowing anatomic, computed tomography (CT) and magnetic
      resonance imaging (MRI) studies of the same anatomic specimen. It proved in
      practice that only a correctly adjusted mixture of different agents allowed
      attainment of this objective. This mixture, composed of gelatin, gadolinium and
      minium, enabled us to attain this end. The description of the technique of
      injecting the vertebral venous plexuses, the difficulties encountered and the
      results of the different imaging techniques are analysed in this study without
      entering into details of the anatomic description. The core of the study consists
      of 11 unembalmed subjects. Three were injected with gelatin mixed with
      gadolinium, one with latex mixed with minium, one with latex mixed with
      gadolinium, and 6 with gelatin mixed with both gadolinium and minium. Only the
      mixture of gelatin-gadolinium-minium allowed study of the same anatomic specimen
      in terms of anatomy, CT and MRI. Two different MRI sequences are described,
      evidence of the different properties of the injection mixture (gelatin,
      gadolinium). The latex-minium mixture gave good CT density but was unsuitable for
      MRI studies. Numerous artifacts caused interference with the radiologic images,
      calling for perfect injection technique. The use of several radiologic techniques
      for a single cadaveric injection allows better correlation of the images, and
      comparison and verification of results between the techniques.

PMID- 9658531
TI  - Study of the inferior oblique muscle of the eye by MRI.
AB  - The utility of the inferior oblique m. radioanatomical study by a FLASH 3D
      sequence in magnetic resonance imaging (MRI). Twenty eyes (ten healthy volunteers
      aged 21-32 years, without any history of significant ocular pathology) were
      explored by MRI (1 Tesla; cranial coil) and comparisons were made between spin
      echo (SE) T1 sequence (through the neuro-ocular and coronal planes; thickness of
      slices = 3 mm) and a gradient echo FLASH 3D sequence (thickness of slices = 1
      mm). This enabled a mm by mm reformation of the inferior oblique m through the
      frontal-oblique plane, made possible by new SE T1 sequences through the same
      plane. Position, height, and signal of the m. were estimated. The mean frontal
      angle formed by the muscle and the sagittal axis measured 29 degrees for the
      right eye and 27 degrees for the left eye. The muscle was always identifiable in
      the reformation despite its thin dimensions: 1.9 mm (1.5 - 2.8) on the right and
      2 mm (1.7 - 2.5) on the left, in low signal silhouetted by the high signal of
      orbital fat. Thus, thanks to mm by mm reconstructions using FLASH 3D sequence, a
      good radioanatomic study of the inferior oblique m. by MRI is possible. This
      could be useful particularly for the strabismus of children.

PMID- 9658532
TI  - Anatomic approach to the parametrium: value of computed tomographic in vitro
      study compared to dissection.
AB  - The aim of this study is to describe the morphology of the normal parametrium by
      correlating the slices obtained with computed tomography of 12 female cadavers
      studies after intravascular injection of latex with the dissection findings in 6
      of the these patients. the upper limit, represented by the isthmus was defined by
      the uterine a. and/or a superficial uterine v. and/or the coronary v. (Charpy).
      The lower limit corresponded to the insertion of the levator ani mm. at the
      junction of the middle and inferior thirds of the vagina. The paracervical and
      paravaginal tissues above the levator ani m. and medial to the pelvic fascia
      covering these muscles were perfectly visualized. The posterior limit, formed by
      the lateral ligament of the rectum and/or the sacrouterine ligaments, and the
      anterior limit determined by the umbilico-vesical fascia were more difficult to
      demonstrate. In this study the parametrium appeared as a highly vascular and
      essentially venous connective structure with a variable morphology dependent on
      the uterine position.

PMID- 9658534
TI  - Partial ureteral duplication in an inverted Y with epididymal ureteric ectopia
      and intrasinusal ureteral junction.
AB  - Partial ureteral duplication in an inverted Y is evidenced by the presence of a
      ureter duplicated at a variable level before reaching the bladder, in either an
      orthotopic or an ectopic position. A case of ureteral duplication at the level of
      the renal hilum with opening of a ureter at the level of the epididymis is
      reported. The description of this original case is compared with the data in the
      literature. The stages of organogenesis of the superior excretory pathway leading
      to ureteral ectopia and ureteral anomalies of number are reviewed.

PMID- 9658533
TI  - Anatomy of spontaneous splenorenal and gastrorenal venous anastomoses. Review of
      the literature.
AB  - Portal hypertension is characterised by the development of a collateral
      portocaval circulation. Among these venous reroutings, some are situated
      posteriorly in the left subphrenic compartment. These are the spontaneous
      splenorenal and gastrorenal anastomoses. Their incidence is estimated at around
      16%. On the one hand, there are the direct shunts, which anastomose the spelling
      v. to the left renal v., of an anecdotal nature, and on the other the spontaneous
      indirect splenorenal shunts, characterised by the presence of a complete
      neurovascular pedicle traversing the gastrophrenic ligament. This relates to the
      gastric collateral v., which is connected to the left renal v. via the inferior
      v. of the left crus of the diaphragm and the middle capsular v., hence the name
      "gastro-phreno-capsulo-renal shunt". At an advanced stage of portal hypertension
      these splenorenal shunts may acquire a major caliber and behave like actual
      surgical shunts.

PMID- 9658535
TI  - Anomalous pancreatico-biliary ductal union with cystic dilatation of the bile
      duct.
AB  - We report, in an adult, an asymptomatic association between cystic dilation of
      the bile duct (type IV A in Todani's classification) and anomalous pancreatico
      biliary ductal union (APBD) with stones in a long common channel. In APBD, the
      connection between the common bile duct and the main pancreatic duct is located
      outside the duodenal wall andis therefore not under the influence of the
      sphincter of Boyden. An abnormally long common channel is in excess of 15 mm. Two
      types of convergence anomalies are defined according to whether the bile duct
      opens into the main pancreatic duct (BP) or the main pancreatic duct into the
      bile duct (PB). In APBD, there is probably a reverse pressure gradient between
      the bile and pancreatic ducts, with regurgitation of pancreatic juice into the
      bile duct, repeated attacks of cholangitis, stenosis and cystic dilatation. A
      long common channel is associated with a higher incidence of carcinoma of the
      gall bladder of the bile duct.

PMID- 9658536
TI  - [The setting up of an integrated veterinary business approach in dairying].
AB  - In addition to the continuous provision of veterinary care, another important
      aspect of a veterinarian's work is his or her advisory function in farm
      management. Too few veterinarians fulfil this function. This can only be done
      successfully if the dairy farmer and veterinarian solve a number of problems. An
      integrated management plan incorporation a step-by-step approach should make this
      possible.

PMID- 9658537
TI  - [The proximal sesamoid bone of the horse; vascular and neurologic
      characteristics].
AB  - Sesamoiditis is characterized clinically by repeated lameness and radiologically
      by changes in the proximal sesamoid bones. This thesis, which was defended in
      June 1997, investigated two characteristics of sesamoiditis, namely the arterial
      blood supply and the innervation of the proximal sesamoid bones, in order to gain
      more insight into the etiopathogenesis of sesamoiditis. Experiments with patient
      material showed that the proximal sesamoid bones have an enormous arterial
      reserve, due in part to the formation of an arterial shift. Moreover, the
      sesamoid bones have their own sensory innervation, provided by a branch of the
      medial and lateral palmar nerve. This branch is called the sesamoid nerve in this
      article. A special technique was developed to anaesthetize this nerve and can be
      used for further differentiation of pastern lameness. That the sesamoid bones are
      sensitive to pain was demonstrated by detection of the so-called nociceptive
      neuropeptides, substance P and calcitonin gene-related peptide, which are
      specifically involved in pain sensation. However, the adjacent ligament appear to
      be even more sensitive. The etiopathogenesis of sesamoiditis is discussed, as are
      a number of clinical implications of pain in the sesamoid bones. A number of
      potential future developments are mentioned.

PMID- 9658538
TI  - [Reproduction of the horse: the use of different dilutions of stallion sperm].

PMID- 9658539
TI  - [Health and social status].

PMID- 9658540
TI  - [Hospital infection caused by Aspergillus--an overview of etiology and
      possibilities for prevention].
AB  - During the last decades a sharp increase in the occurrence of invasive
      aspergillosis associated with a high mortality has been observed. This fact is
      mainly due to an increase in the number of immunosuppressed patients. Nosocomial
      aspergillosis usually is of exogenous origin and often related to building
      construction and reconstruction, road construction, contaminated ventilation
      systems and contaminated soil of pot plants. By institution of suitable
      prophylactic measures a reduction of incidence and mortality of invasive
      aspergillosis can be achieved. This review gives a short introduction into the
      epidemiology, pathogenesis and diagnosis of invasive aspergillosis and, in the
      second part summarizes internationally recommended guidelines for prevention of
      this severe complication.

PMID- 9658541
TI  - Social inequalities in disability-free and healthy life expectancy in Austria.
AB  - The purpose of this study is to describe socioeconomic differences in the health
      status and mortality of the Austrian population. Socioeconomic differentials in
      disability and self-perceived health are studied on the basis of educational
      groups. The data are drawn from the 1991 Austrian micro-census on health and from
      linked death and census records for the years 1981/82. The maximum number of
      years lived between ages 30 and 75 is divided into years lost, years lived in
      disability or poor health and years lived without disability or in good health.
      Our findings clearly indicate a correlation between higher education and higher
      life expectancy and lower morbidity. Comparing the two indicators, more years are
      lived in poor health than in severe functional disability. The two concepts of
      health lead to different conclusions when results for men and women are compared:
      women live more years in disability than men but fewer years in poor health.
      Differences between educational groups are lower when the concept of self
      perceived health is applied.

PMID- 9658542
TI  - Survey of sport injuries in physical education students participating in 13
      sports.
AB  - A protocolled interview was carried out of 150 physical education students to
      specify retrospectively all sports injuries sustained during their training. This
      study analyses the frequency, severity and location of injuries sustained by a
      population group participating in 13 different sports. On average more than three
      injuries were encountered per student over a mean period of 2.35 years. 74% of
      all 482 recorded injuries were sustained by males. The sports associated with the
      highest rate of injuries were gymnastics, skiing and athletics followed by ball
      games. The most frequently injured body regions were the ankle and the hand. 29%
      of the injuries were regarded as being severe.

PMID- 9658543
TI  - [The postictal state. A clinically oriented observation of patients with
      epilepsy].
AB  - Epileptic seizures are followed by dynamic alterations in neurologic function in
      the postictal period which have received little attention by clinicians over a
      long period of time. We therefore retrospectively studied videotapes of 160
      patients with focal epilepsy who underwent presurgical evaluation, for the
      occurrence of postictal symptoms to determine whether these phenomena have any
      localizing or lateralizing value in defining the seizure onset zone. RESULTS: (1)
      We found postictal paresis in 22 of 160 patients (18.8%) in each case
      contralateral to the hemisphere of seizure onset. (2) 'Perservative' automatisms
      which start during the ictus and continue in the postictal period occurred in
      25.2% of 135 patients with temporal lobe epilepsy but not in patients with
      frontal lobe epilepsy. (3) Sexual automatisms defined as manipulations of the
      genitals were found exclusively in patients with temporal lobe epilepsy (in 5.9%
      of 135 patients). (4) Postictal 'Nose-wiping' was evident in 51.3% of 76 temporal
      lobe epilepsy patients but only in 12.0% of 25 extratemporal lobe epilepsy
      patients and was performed with the hand ipsilateral to the hemisphere of seizure
      onset in 86.5% of all temporal lobe seizures. (5) Postictal language disturbances
      were observed only in patients with temporal lobe epilepsy (34% of 97 patients)
      and pointed to a seizure onset in the dominant hemisphere in 80.8%. We conclude
      that postictal phenomena can provide reliable information for the localization of
      the seizure onset zone in patients with complex partial seizures. Thus, more
      attention should be given to the postictal state during presurgical epilepsy
      monitoring.

PMID- 9658544
TI  - [Aspects of laterality for surgical indications in middle ear diseases].

PMID- 9658545
TI  - [How dangerous is genetically engineered food].

PMID- 9658546
TI  - [LDL subfractions and coronary heart disease--an overview].
AB  - Low density lipoproteins are heterogeneous in particle size, density, and
      physical as well as chemical properties. Regarding size and density, LDL can be
      divided into two main profiles, LDL pattern A with elevated concentration of
      large, buoyant LDL particles and LDL pattern B with increased concentration of
      small, dense LDL particles. The latter is particularly expressed in insulin
      resistance and is associated with elevated serum triglycerides and reduced
      concentrations of HDL and particularly HDL2 cholesterol. The LDL profile of
      increased concentration of small, dense LDL particles has shown to be associated
      with an increased risk of cardiovascular events. The LDL profile is partly
      genetically determined, but can be improved by non-pharmacological (exercise,
      diet) and pharmacological intervention. It remains to be confirmed whether the
      LDL subfraction profile is an independent lipid risk factor besides HDL2
      cholesterol and triglycerides, but it is certainly a valuable indicator assessing
      metabolic cardiovascular risk.

PMID- 9658547
TI  - [Heart operations for heart tumors in Germany--results of 1996 survey].
AB  - In the Federal Republic of Germany, no data existed regarding the frequency of
      open heart surgery for excision of cardiac neoplasms. Therefore, a standard
      questionnaire concerning heart tumors was sent to all 77 German heart centers
      performing cardiac surgery. Data from 65 of the 77 heart centers (= 84%) are
      finally available: 187 patients were operated upon for myxomas, only 44 upon for
      non-myxomatous cardiac tumors (28 of them with malignant primary or secondary
      lesions of the heart). In 1996, 0.32% (231/72,763) of all surgical procedures
      using a heart-lung machine (registered 72,763 of 87,372 total) were aimed at
      excision of heart tumors. Based on surgical data, the incidence of solely the
      primary tumors of the heart in Germany is at least 3 per million population per
      year (253 tumors/81.814 million inhabitants). Even if small tumors are
      asymptomatic and remain undetected, today, the majority of primary tumors of the
      heart will be revealed by echocardiography, computer tomography, and magnetic
      resonance imaging, and these patients are usually referred to operation. Thus, in
      Germany, about 0.3% of operations using a heart-lung machine were performed for
      cardiac tumors-among these, myxomas are clearly predominant.

PMID- 9658548
TI  - [Advantages in using intravascular ultrasound in percutaneous transluminal
      coronary angiography].
AB  - Recent randomized clinical trials reported a reduction of restenosis using
      intracoronary stents and suggested that this restenosis reduction is a result of
      the higher immediate luminal gain in comparison to conventional percutaneous
      transluminal coronary angioplasty (PTCA). The hypothesis of this study is based
      on the assumption that IVUS guided PTCA leads to equivalent long term PTCA
      results as compared to PTCA and the additional placement of a stent. Thus, the
      purpose of this non-randomized single center study was to evaluate (1) the safety
      and efficacy and (2) the long term outcome of vessel size adapted PTCA in
      patients with native coronary lesions. From April 1995 to March 1996 the
      morphological dimensions of the target lesions were determined in 107 patients
      with 108 lesions by intravascular ultrasound prior to conventional balloon
      angioplasty. Quantitative parameters of the vascular dimensions were assessed on
      line and the diameter of the balloon catheter was adapted to the external elastic
      membrane (EEM) at the lesion site minus 10%. Using this strategy, mean balloon
      diameter was 4.1 +/- 0.5 mm. Acute and one year clinical follow-up results were
      obtained in all 107 patients. Angiographic success was defined as a final percent
      diameter stenosis of < 30%. The following criteria determined by
      postinterventional IVUS were also used to define a successful PTCA: luminal CSA
      gain of > 30% with an angiographically patent flow (TIMI 3). Acute events
      occurred in two patients (one death and one successful acute surgical
      revascularisation). During one year follow-up, 11 patients had a clinical event
      including death, Q-wave MI, surgical revascularisation, and repeat PTCA. In 83
      patients (78%), control angiography was performed and revealed an angiographic
      restenosis rate of 21% using the NHLBI criterion of a diameter stenosis > 50%
      CONCLUSION: The use of balloon diameters following these measurements is safe in
      the acute setting with a low number of in hospital events and effective in
      reducing clinical events as well as angiographic restenosis rates during one year
      follow-up. These promising results warrant verification in larger scale
      randomized trials.

PMID- 9658549
TI  - [Optimal expansion of the multi-link stent. An in vitro study with high
      resolution roentgen technique].
AB  - It has been speculated that high pressure implantation may improve the results of
      coronary stenting. However, this method bears the risk of persistent dissection
      and may increase late lumen loss. Presently, there is no consensus about the
      optimal stent implantation technique with the regard to balloon size and
      pressure. To elucidate this question an experimental study was performed in a
      coronary stenosis model. 3.5 mm Multi-Link (ML) stents were implanted in 3.3 mm
      silicone rubber tubes containing 50% concentric narrowings. Three implantation
      techniques were applied: 1. The standard technique using the conventional ML
      delivery system with a compliant balloon (ML-ST). 2. A new deployment method with
      a high pressure delivery system (ML-HP). 3. "Focal postdilation" using the ARC
      catheter, which has a special balloon with an inner compliant and an outer non
      compliant section (ML-ARC). For comparison, the Palmaz-Schatz stent was implanted
      by using a high pressure balloon. Stent expansion was imaged by magnification
      radiography. Minimal lumen diameter within the stent (MLD) and the lumen diameter
      outside the stent (BD) were measured after dilations with 6, 9, 12, 15, 18, and
      21 atm. The relation of the BD to the MLD was used as an index of vessel trauma.
      The results lead to the following conclusions: 1. A complete apposition to the
      vessel wall for a balloon/vessel relation of 1.1:1 could not be reached with
      pressures below 9-15 atm. The increase of the pressure beyond 15 atm resulted
      only in a minimal additional lumen. 2. Compared to the Palmaz-Schatz stent the
      recoil of the ML stent was significantly lower. 3. For all three implantation
      techniques the ML-ARC showed the best results with the maximal dilation of the
      stenotic vessel-area and the minimal expansion of the vessel outside the stent.

PMID- 9658550
TI  - [Repetitive monomorphic ventricular tachycardia (Gallavardin type): clinical and
      electrophysiological characteristics in 20 patients].
AB  - Repetitive monomorphic ventricular tachycardia (RMVT) is defined by the presence
      of numerous monomorphic isolated, premature ventricular complexes, couplets, and
      runs of unsustained ventricular tachycardia having the same morphology in
      patients without structural heart disease. Patients with RMVT mostly demonstrate
      the typical left bundle branch block morphology with normal or rightward axis
      during tachycardia. At our institution, 20 patients with RMVT have been
      systematically studied: a syncope had occurred in 35% of our patients, in three
      cases a syncope was the first manifestation of the RMVT. Of our RMVT patients,
      25% developed sustained episodes (> 3 min) of ventricular tachycardia as
      documented by Holter ECG. The salvos of ventricular tachycardia are generally
      short in RMVT. This behavior and the typical exercise dependence differentiates
      RMVT from paroxysmal sustained idiopathic ventricular tachycardia. Exercise
      testing is mandatory for correct diagnosis of RMVT. In our institution, 85-90% of
      RMVT patients demonstrated runs of ventricular tachycardia or sustained
      ventricular tachycardia while on a treadmill (exercise test) or during
      isoproterenol infusion. RMVT was inducible by programmed electrical right
      ventricular stimulation in only 13% of our patients. Therefore, in patients with
      suspected RMVT programmed electrophysiological stimulation is only useful to
      differentiate a ventricular tachycardia from a supraventricular tachycardia with
      bundle brunch block or in patients with unexplained syncope. The prognosis is
      considered generally good; in our patients no life threatening ventricular
      tachyarrhythmias were observed during a follow-up of up to 4 years. Verapamil and
      beta-adrenoceptor antagonists generally offer symptomatic improvement. In some
      cases treatment with a class III antiarrhythmic agent is necessary. While drug
      refractory paroxysmal sustained idiopathic ventricular tachycardia can be abladed
      with both immediate and long-term success, catheter ablation of RMVT is only
      rarely indicated.

PMID- 9658551
TI  - [High frequency catheter ablation in young patients with permanent junctional
      reentry tachycardia and ectopic atrial tachycardia].
AB  - Ten young patients with a median age of 10.5 (range: 6 to 31) years suffering
      from the permanent form of junctional reciprocating tachycardia (PJRT; n = 7) and
      ectopic atrial tachycardia (AET; n = 3) were treated by transcatheter
      radiofrequency current application. Indications for interventional therapy were
      failure of medical therapy after a median of 3 antiarrhythmic drugs in all
      patients, syncope in 1, and impaired left ventricular function in 4 patients
      (PJRT n = 3, AET n = 1). The intervention was primarily successful in all
      patients. Median fluoroscopy time during the ablation procedure was 17 (10 to 70)
      minutes. A median of 3 (1 to 14) radiofrequency (500 kHz) pulses was delivered at
      a target temperature of 70 degrees C or with 30 W for 30 s. One patient had a
      recurrence of PJRT and was successfully treated by a repeat ablation. After a
      median follow-up of 14 (2 to 61) months, all patients are free of drug treatment
      and in normal sinus rhythm. Left ventricular function has normalized in patients
      with follow-up > 6 months. Radiofrequency catheter ablation was a safe and
      effective therapy in young patients with drug-resistant forms of chronic
      permanent supraventricular tachycardia.

PMID- 9658552
TI  - [Effect of programmed safety margin on function time of modern dual chamber
      pacemakers].
AB  - In 55 consecutive patients with the same dual chamber pacemaker (Relay,
      Intermedics) and different pacing leads, the influence of different safety
      margins for pacing on battery current was investigated. 2.8 +/- 0.9 years after
      implantation, atrial and ventricular pulse-width thresholds (tRS) (ms) were
      determined at 0.5, 1.0, and 2.0 V, and the charge delivered at threshold was
      telemetered. If tRS was < 1.50 ms at 0.5 V, an amplitude of 1.0 V was programmed
      in the atrium and the ventricule; if tRS was < 1.50 ms at 1.0 V, then an
      amplitude of 2.0 V was chosen. Two times the charge threshold (2 x QRS), two
      times the voltage threshold (2 x URS), and three times the pulse-width threshold
      (3 x tRS) were programmed as the safety margins for pacing. With every safety
      margin, battery current (IBat) (microA) was averaged from 5 telemetric readings
      in D00 mode with 70 bpm. IBat was significantly lower with 2 x QRS as compared
      with 2 x URS (13.43 +/- 1.0 vs. 14.20 +/- 1.2 microA, p < 0.01) and as compared
      with 3 x tRS (13.99 +/- 1.2 microA, p < 0.05). Pacemaker longevity derived from
      these current data was significantly longer with 2 x QRS (112 +/- 8 months) as
      compared with 2 x URS (106 +/- 9, p < 0.01) and as compared with 3 x tRS (108 +/-
      8, p < 0.05). If current consumption is compared intraindividually in dependance
      on the programmed amplitude, battery current is significantly lower at 1.0 V as
      compared with 2.0 V resulting in a mean reduction of 0.63 microA (-4.9%, p <
      0.05) and an average gain in longevity of 5 months. This applies to every safety
      margin tested. Differences in battery current caused by the safety margins will
      translate into a greater gain in longevity in future pacemaker models with
      reduced internal current consumption.

PMID- 9658553
TI  - [Transient loss of preexcitation by acute coronary ischemia--a case report].
AB  - We present a case of WPW syndrome with an accessory pathway in the right free
      wall. Two prolonged and failed attempts at radiofrequency catheter ablation of
      this accessory pathway in other institutions led to a third attempt in our
      hospital. With a 7F catheter in the right coronary artery, transient ischemia in
      the right ventricular myocardium developed with consecutive loss of bidirectional
      preexcitation within 45 seconds prior to catheter ablation. Removal of the
      guiding catheter, while the mapping catheter in the coronary artery was still in
      place, was reproducibly followed by the reoccurrence of the preexcitation
      pattern. Successful outcome of accessory pathway ablation was achieved by mapping
      the right free wall using an intracoronary catheter in the right coronary artery
      and ablating the accessory pathway using a modified long vascular sheet.

PMID- 9658554
TI  - [Haustration of the ascending aorta as differential diagnosis of aortic
      dissection].
AB  - Suspected aortic dissection requires undelayed diagnosis by use of imaging
      modalities such as transesophageal ultrasound, contrast enhanced computed
      tomography (CT), or magnetic resonance imaging (MRI). This case report describes
      an asymptomatic man with echocardiographic suspicion of aortic arch dissection.
      The discordance with the clinical presentation led to CT, MRI, and eventually to
      contrast angiography, eventually confirming extensive haustration of the thoracic
      aorta and excluding any acute or chronic dissection. This case demonstrates
      haustration of the thoracic aorta as a potential differential diagnostic problem
      when solely using ultrasound techniques.

PMID- 9658555
TI  - Pseudoacids. II. 2-Acylbenzoic acid derivatives.
AB  - Structures of derivatives of cyclic o-acylbenzoic acids, including the chloride,
      endo- and exocyclic amides, esters and anhydrides, are examined. 3-Chloro-1(3H)
      isobenzofuranone (1), orthorhombic, Pbca, a = 11.616 (5), b = 8.120 (3), c =
      15.640 (9) A; 3-methoxy-3-phenyl-1(3H)-isobenzofuranone (3), orthorhombic,
      P2(1)2(1)2(1), a = 6.923 (2), b = 8.291 (4), c = 21.551 (8) A; 3-hydroxy-3-phenyl
      N-propyl-1(3H)-isoindolone (4), orthorhombic, P2(1)2(1)2(1), a = 8.662 (4), b =
      9.551 (7), c = 17.649 (14) A; 3-(N-morpholino)-1(3H)-isobenzofuranone (5),
      triclinic, P1, a = 6.172 (4), b = 11.163 (7), c = 17.33 (2) A, alpha = 105.91
      (6), beta = 99.85 (6), gamma = 97.57 (5) degrees; 3-(2'-benzoylbenzoyloxy)-3
      phenyl-1(3H)-isobenzofuranone (7), triclinic, P1, a = 9.694 (3), b = 10.505 (4),
      c = 11.163 (4) A, alpha = 80.58 (3), beta = 80.41 (3), gamma = 76.49 (3) degrees;
      bis[1(3H)-isobenzofuranone-3-yl]ether (8), monoclinic, I2/a, a = 15.31 (2), b =
      6.111 (12), c = 28.30 (5) A, beta = 101.61 (12) degrees. An open oxoacid tertiary
      amide is also described: N-morpholino 2'-benzoylbenzamide (6): monoclinic,
      P2(1)/c, a = 6.844 (4), b = 15.696 (8), c = 14.154 (7) A, beta = 99.43 (4).
      Pseudoacid derivatives form planar isobenzofuran and isoindole rings, and the
      former aldehyde/ketone carbon-heteroatom endocyclic and exocyclic bond distances
      show bond length variations which correlate with the relative basicities of the
      attached groups. Structures of both endocyclic and exocyclic nitrogen
      pseudoamides are reported as well as examples of the normal-pseudoanhydride and
      the dipseudoanhydride.

PMID- 9658556
TI  - Localization of the proenzyme form of the vitellin-processing protease in
      Blattella germanica by affinity-purified antibodies.
AB  - During Blattella germanica embryo development, the nutritive yolk protein
      vitellin is processed by a cysteine protease, which is activated proteolytically
      from a proprotease during acidification of yolk granules. A murine polyclonal
      antiserum was generated with the purified proprotease as the immunogen. The
      antiserum was made monospecific to proprotease by subtractive affinity
      chromatography using proprotease-free yolk proteins as ligand. The purified
      antibodies were employed to investigate the temporal and spatial expression of
      the proprotease during vitellogenesis and embryo development. Anti-proprotease
      reactive peptides appeared in extracts of fat bodies and ovarian follicles of
      post-mating females, but not in fat bodies of males or the fat bodies or
      follicles of unmated females, suggesting that the proprotease is synthesized
      extraovarially. Use of the antibodies was extended to monitor the kinetics of
      proprotease disappearance during early embryo development.

PMID- 9658557
TI  - Hemagglutinating properties of apolipophorin III from the hemolymph of Galleria
      mellonella larvae.
AB  - In search for factors that cause encapsulation of foreign bodies in insect
      hemolymph we discovered that larval hemolymph of Galleria mellonella caused
      aggregation of mammalian erythrocytes. The hemagglutinating agent was identified
      as an 18-kDa protein that did not react with lectins. The sequence of 81 amino
      acids in three protein fragments and the properties of the protein revealed that
      it was Galleria homologue of apolipophorin III (apoLp-III). ApoLp-III was found
      in high amounts in the hemolymph of Galleria larvae, pupae, and adults, as well
      as in the molting fluid. The hemagglutinating action of the whole hemolymph or
      the purified apoLp-III was independent of the presence of sugars in the medium.
      This indicated that it was not mediated by carbohydrates on the erythrocyte
      surface. The hemagglutination was inhibited at low pH (3.0), in the absence of
      calcium ions, and in the presence of certain bacterial lipopolysaccharides or
      their essential component, the 2-keto-3-deoxyoctonate-3-deoxyoctulosonic acid
      (KDO). It is suggested that interaction of apoLp-III with lipopolysaccharides in
      bacterial cell walls may play a role in insect immune reactions.

PMID- 9658558
TI  - Actions of the pyrethroid insecticides cismethrin and cypermethrin on house fly
      Vssc1 sodium channels expressed in Xenopus oocytes.
AB  - Voltage-sensitive sodium channels encoded by the Vssc1 gene of the house fly
      (Musca domestica) were expressed in Xenopus laevis oocytes in combination with
      the tipE gene product of Drosophila melanogaster and were characterized by two
      electrode voltage clamp. Vssc1/tipE sodium channels expressed in oocytes were
      highly sensitive to tetrodotoxin; half-maximal inhibition of sodium currents by
      tetrodotoxin was obtained at a concentration of 2.4 nM. Cismethrin, a pyrethroid
      that produces Type I effects on intact nerve, slowed the inactivation of sodium
      currents carried by Vssc1/tipE channels during a depolarizing pulse and induced a
      tail current after repolarization that decayed with a first-order time constant
      of approximately 650 ms. The voltage dependence of activation and steady-state
      inactivation of cismethrin-modified channels were shifted to more negative
      potentials. Cypermethrin, a pyrethroid with Type II effects on intact nerve, also
      prolonged the inactivation of Vssc1/tipE sodium channels and induced a tail
      current. However, the cypermethrin-induced tail current was extremely persistent,
      decaying with a first-order time constant of approximately 42 s. Unlike
      cismethrin, the effect of cypermethrin was use dependent, requiring repeated
      depolarizing pulses for the full development of modified sodium currents. The
      divergent effects of cismethrin and cypermethrin on Vssc1/tipE sodium channels
      expressed in oocytes are consistent with the actions of these and related
      compounds on sodium channels in invertebrate and vertebrate nerve preparations
      and provide insight into the mechanisms underlying the production of Type I and
      II effects on neuronal excitability.

PMID- 9658559
TI  - Isolation and sequence of a partial vitellogenin cDNA from the cockroach,
      Blattella germanica (L.) (Dictyoptera, Blattellidae), and characterization of the
      vitellogenin gene expression.
AB  - A partial cDNA clone of the vitellogenin gene from the cockroach Blattella
      germanica has been isolated from a cDNA expression library using an anti-vitellin
      vitellogenin antiserum probe. The analysis of cDNA inserts gave a sequence of
      2,645 nucleotides corresponding to the 3' region. The deduced amino acid sequence
      is 825 residues long and is similar to the homologous portion of the vitellogenin
      of other insect species, especially that of the mosquito Aedes aegypti. RNA
      hybridization studies indicated that the vitellogenin gene expression is limited
      to the fat body of adult females. The pattern of expression during the first
      vitellogenic cycle was approximately parallel to that of vitellogenin production
      by the fat body previously described. The availability of a cDNA probe for the B.
      germanica vitellogenin gene represents a useful tool to study the molecular
      action of hormones affecting vitellogenin synthesis in this species.

PMID- 9658560
TI  - Effect of culture medium on the in vitro secretion activity of prothoracic glands
      from Pseudaletia separata.
AB  - The prothoracic glands (PGs) taken from the last instar of the common armyworm,
      Pseudaletia separata, were cultured in various media for the purpose of finding a
      suitable medium for relatively long-term culture of PGs. Among the tested culture
      media, MGM-450 medium without serum was the best to maintain PG cells viable for
      relatively long periods, and to continue to secrete ecdysteroids. Secretion of
      ecdysteroid by the PG in vitro became marked when the PG was taken from last
      instar larvae older than 2 days after the last molt. PGs cultured in any of the
      media secreted ecdysteroid only within the first 2 h after placing them in
      culture, however, in the MGM-450 medium, the PGs secreted ecdysteroid even after
      5 days of culture.

PMID- 9658561
TI  - The response to domestic violence in a model court: some initial findings and
      implications.
AB  - This study utilized a non-experimental design to obtain information on a full
      range of domestic violence incidents brought before the Quincy, Massachusetts
      District Court, a model court. One limitation of previous research on spouse
      assaults using more sophisticated designs is that the target population has been
      restricted to specific subgroups of cases thereby limiting subsequent discussions
      of policy/practice implications of the findings vis-a-vis all spouse assault
      cases. To address this research "shortfall", we obtained permission from the
      Quincy District Court to examine all the spouse assault cases brought before the
      court during a 7-month period (June, 1995, through February, 1996). The findings
      show that in a full enforcement environment, victims took out restraining orders
      only against the most violent, criminally abusive men. Most men who were arrested
      for domestic violence had prior criminal histories for a variety of offenses.
      Domestic violence offenders appeared to be of two types: those with extensive and
      diverse criminal histories and those with little or no such involvement. However,
      active criminal justice intervention against domestic violence offenders appears
      to be primarily directed toward offenders already active in the criminal justice
      system.

PMID- 9658562
TI  - The description of gay and lesbian families in second-parent adoption cases.
AB  - Lesbians and gay men are turning to the courts to recognize their family
      relationships. In this article every reported court decision where a lesbian or
      gay couple has successfully completed a second-parent adoption is reviewed to
      analyze the presentation and judicial analysis of the petitioning parties in
      conjunction with the current debates within family theory. Traditional family
      theorists argue that the contemporary family is in transition but will always be
      recognizable as the traditional family; postmodern theorists argue that the
      traditional "family" is a fiction. Results from this study indicate that judges
      in second-parent adoption cases rely on a traditional definition and vision of
      the family in evaluating the gay and lesbian petitioners before them.

PMID- 9658563
TI  - Emotional maltreatment in adolescents' everyday lives: furthering sociolegal
      reforms and social service provisions.
AB  - The article examines sociolegal responses to adolescent victimization,
      particularly responses to the emotional dimensions of their violent personal
      relationships. The investigation reveals how the legal system generally fails to
      recognize youth's emotional maltreatment. Responses tend to consider emotional
      maltreatment as subordinate and secondary to some legally prohibited sexual and
      physical assaults. Rather than casting emotional dimensions as ancillary to a
      narrowly delimited set of sexual and physical assaults, this article proposes
      that efforts to counter emotional maltreatment become the centerpiece of efforts
      to understand adolescents' violent relationships; that it become central in the
      design of policies aimed to foster adolescent development; and that no existing
      legal rules or policy considerations prevent further recognition of adolescents'
      legal right to protection from emotional maltreatment.

PMID- 9658564
TI  - New enzymatic synthesis of 6(3)-modified maltooligosaccharides and their
      inhibitory activities for human alpha-amylases.
AB  - Ten new 6(3)-modified maltopentaoses and tetraoses were synthesized by enzymatic
      reactions utilizing cyclodextrin glycosyltransferase (EC 2.4.1.19) and subsequent
      human salivary alpha-amylase (HSA) (EC 3.2.1.1). Among these compounds, alpha-D
      glucopyranosyl-(1-->4)- alpha-D-glucopyranosyl-(1-->4)-(6-deoxy-alpha-D
      glucopyranosyl)-(1-->4)- alpha-D-glucopyranosyl-(1-->4)-D-glucopyranose (11) and
      alpha-D-glucopyranosyl-(1-->4)-(6-deoxy-alpha-D-glucopyranosyl)-(1-->4)- alpha-D
      glucopyranosyl-(1-->4)-D-glucopyranose (12) showed strong inhibitory activities
      for human pancreatic alpha-amylase (HPA) and HSA. The IC50 of 6(3)
      deoxymaltopentaose 11 (8.0 x 10(-5) M for HPA, 1.0 x 10(-4) M for HSA) and 6(3)
      deoxymaltotetraose 12 (2.0 x 10(-3) M for HPA, 2.0 x 10(-3) M for HSA) were lower
      than that of 6(3)-deoxymaltotriose [(6-deoxy-alpha-D-glucopyranosyl)-(1-->4)
      alpha-D- glucopyranosyl-(1-->4)-D-glucopyranose 13; 2.0 x 10(-3) M for HPA, 4.2 x
      10(-2) M for HSA].

PMID- 9658565
TI  - The synthesis of neoglycophospholipid conjugates via reductive amination of omega
      oxoalkylglycosides and phosphatidylethanolamines.
AB  - Phospholipid conjugates of mono- and disaccharides tethered with an n-decanyl
      spacer were efficiently synthesized via an improved reductive amination of
      deprotected omega-oxodecanyl beta-glycosides and phosphatidylethanolamines with
      or without alkenyl groups. The omega-oxodecanyl beta-glycosides were prepared by
      stereoselective glycosidation of glycosyl halides with 1, 10-decanediol followed
      by pyridinium dichromate oxidation. The acetyl groups of the omega-oxodecanyl
      beta-glycosides were removed with sodium methoxide prior to their conjugation
      with phosphatidylethanolamines.

PMID- 9658566
TI  - Synthesis of alpha-glucosidase inhibitors: kojibiose-type pseudo-disaccharides
      and a related pseudotrisaccharide.
AB  - Two kojibiose-type pseudo-disaccharides and a trisaccharide, containing a 5-amino
      1,2,3,4-cyclopentanetetrol derivative or valienamine, linked by way of nitrogen
      bridges to the sugar residues, have been designed and synthesized as processing
      alpha-glucosidase I inhibitors. Synthesis of the pseudo-disaccharides was carried
      out starting from the coupling products of the sugar isothiocyanates and an
      aminocyclitol, respectively, by cyclization with mercury(II) oxide to the cyclic
      isoureas and subsequent deprotection. Pseudokojibiose was prepared in a poor
      yield by reaction of a protected valienamine and a sugar epoxide, followed by
      deprotection. Although the pseudooligosaccharides are all strong inhibitors of
      alpha-glucosidase (baker's yeast), they did not have any inhibitory potency
      against either sucrase isomaltase (rat intestine) or processing alpha-glucosidase
      (rat liver microsomes).

PMID- 9658567
TI  - The structure of the exocellular polysaccharide from the cyanobacterium
      Cyanospira capsulata.
AB  - The exocellular polysaccharide produced by the cyanobacterium Cyanospira
      capsulata has been subjected to partial acid hydrolysis and N-deacetylation
      nitrous acid deamination. The oligosaccharides released have been isolated by
      weak anion exchange and aqueous size exclusion chromatography, and characterized
      by a combination of 1D and 2D nuclear magnetic resonance spectroscopy, mass
      spectrometry, sugar composition and linkage analyses. The polysaccharide has an
      octasaccharide repeating unit with the following structure: [formula: see text]

PMID- 9658568
TI  - Structural analysis of the exopolysaccharides produced by Lactobacillus spp. G
      77.
AB  - The exopolysaccharide produced by a ropy strain of Lactobacillus spp. G-77 in a
      semi-defined medium, was found to be a mixture of two homopolymers composed of D
      Glc. The two poly-saccharides were separated and, on the basis of monosaccharide
      and methylation analyses, 1H, 13C, 1D and 2D NMR experiments, one of the
      polysaccharides was shown to be a 2-substituted-(1-3)-beta-D-glucan, identical to
      that described for the EPS from Pediococcus damnosus 2.6 (M.T. Duenas-Chasco,
      M.A. Rodriguez-Carvajal, P. Tejero-Mateo, G. Franco-Rodriguez, J. L. Espartero,
      A. Irastorza-Iribar, and A.M. Gil-Serrano, Carbohydr. Res., 303 (1997) 453-458),
      and the other polysaccharide was shown to consist of repeating units with the
      following structure [formula: see text]

PMID- 9658569
TI  - Glycosphingolipids of skeletal muscle: I. Subcellular distribution of neutral
      glycosphingolipids and gangliosides in rabbit skeletal muscle.
AB  - Membrane vesicles were prepared from rabbit skeletal muscle, separated by sucrose
      density gradient centrifugation and characterized by their specific marker
      enzymes, ligand binding, and ion flux activities. The fractions obtained (in the
      order of increasing density) were sarcolemma (SL), T-tubules (TT), sarcoplasmic
      reticulum (SR1 and SR2) and triads/mitochondria (Tr/M). Their glycosphingolipid
      compositions were analyzed by biochemical and immunochemical methods with
      specific antibodies (TLC immunostaining) and characteristic patterns were
      obtained from respective membrane fractions, expressed on a protein basis.
      Glucosylceramide, the main neutral glycosphingolipid of rabbit muscle, was found
      in SL and TT fractions, whereas SR and Tr/M vesicles lack this compound.
      Lactosylceramide was selectively recovered in the SR1 fraction. GM3(Neu5Ac), the
      main ganglioside in rabbit muscle, was found to account for 64% in the SL, 13% in
      the TT, 7% in the SR1, 3% in the SR2 and 13% in the Tr/M fractions. IV3Neu5Ac
      nLcOse4Cer was mostly abundant in SL and decreased in the order SL > TT, Tr/M >
      SR1, SR2. IV6Neu5Ac-nLcOse4Cer was only detected in the SL and Tr/M fractions in
      noteworthy quantities. Ganglioseries gangliosides GM1, GD1a, GD1b and GT1b
      displayed homogeneous distribution patterns in each membrane preparation. They
      were expressed only in small amounts but mainly in SL, TT and Tr/M vesicles and
      to less extent in SR1 and SR2 fractions. The presence of GM3(Neu5Ac) in the SL as
      well as on subcellular level was confirmed in transverse muscle cryosections by
      means of indirect immunofluorescence microscopy. The SL was brightly stained, but
      considerable intracellular fluorescence was observed as expected from the
      biochemical analyses. Thus, the neutral GSL and ganglioside expression of the SL
      and the intracellular membraneous network is different in skeletal muscle both in
      terms of quantitative and qualitative GSL composition as demonstrated in details
      by means of biochemical and immunochemical techniques. The modulatory functions
      of GM3 and gangliosides of the neolacto- and ganglio-series towards the voltage
      dependent Ca(2+)-channel, largely preponderant in the triads-containing Tr/M
      fraction, is the subject of the accompanying paper (J. Muthing, U. Maurer, and S.
      Weber-Schurholz, Carbohydr. Res., 307 (1998) 147-157).

PMID- 9658570
TI  - Glycosphingolipids of skeletal muscle: II. Modulation of Ca2(+)-flux in triad
      membranes by gangliosides.
AB  - Membrane vesicles of rabbit skeletal muscle were prepared and separated by
      sucrose density gradient centrifugation. The fractions obtained (in the order of
      increasing density) were sarcolemma (SL), T-tubules (TT), sarcoplasmic reticulum
      (SR1 and SR2) and triads/mitochondria (Tr/M) as characterized by their specific
      marker enzymes, ligand binding, and ion flux activities. The distribution of
      neutral glycosphingolipids and gangliosides in these membrane preparations has
      been documented in the preceding paper (J. Muthing, U. Maurer, U. Neumann, B.
      Kniep, and S. Weber-Schurholz, Carbohydr, Res., (1988) 135-145). GM3(Neu5Ac) is
      the dominant ganglioside, neolacto-series gangliosides are moderately expressed
      and ganglio-series gangliosides were found in minor quantities, however, all
      showing different qualitative and quantitative membrane-type specific patterns.
      The voltage dependent Ca(2+)-channels of skeletal muscle reside prevalently in
      the triad enriched membrane fractions deduced from highest binding capacity of
      1,4-dihydropyridines. Calcium channel complexes of triads were reconstituted into
      unilamellar phospholipid vesicles of 400 nm defined size and the active 45Ca(2+)
      uptake into intravesicular space was measured after incorporation of muscle
      specific gangliosides into the outer vesicle lipid bilayer in parallel to control
      liposomes without gangliosides. GM3(Neu5Ac) strongly increased the uptake of
      45Ca2+ (+285%) whereas GM3(Neu5Gc) severely inhibited the ion flux (-61%).
      Neolacto-series gangliosides evoked miscellaneous effects upon 45Ca(2+)-flux
      depending on isomeric sialic acid configuration, oligosaccharide size and fatty
      acid chain length of the ceramide portion. VI3Neu5Ac-nLcOse6Cer (C24-fatty acid),
      IV3Neu5Ac-nLcOse4Cer (C16-fatty acid) and IV6Neu5Ac-nLcOse4Cer (C16-fatty acid)
      strongly enhanced the 45Ca(2+)-flux (+208, +162, and +120%, respectively, whereas
      IV3Neu5Ac-nLcOse4Cer (C24-fatty acid), VI3Neu5Ac-nLcOse6Cer (C16-fatty acid) and
      IV6Neu5Ac-nLcOse4Cer (C24-fatty acid) slightly reduced 45Ca(2+)-flux (-3, -6, and
      -17%, respectively). Out of all gangliosides tested in this study, GM1 showed the
      strongest stimulatory effect (+327%). GD1a and GT1b gave rise to remarkable flux
      stimulation of +283 and +255%, respectively, whereas GD1b exhibited only a
      slightly positive effect (+38%). This data suggest a functional role of
      gangliosides in subcellular muscle membranes giving strong evidence that
      gangliosides are capable of modulating the cytosolic calcium level of muscle,
      which regulates muscle contraction.

PMID- 9658571
TI  - Reinvestigation of the O-specific polysaccharides of Hafnia alvei
      lipopolysaccharides isolated from strains ATCC 13337 and 1187.
AB  - The structure of the O-specific polysaccharides of the lipopolysaccharides
      produced by Hafnia alvei strains ATCC 13337 and 1187 was reinvestigated. The
      position of phosphate group in the repeating units of the polysaccharides was
      established with the aid of 1H detected, 31P edited NMR spectra. According to the
      results obtained, the polysaccharides are teichoic acid-like polymers with the
      repeating units of the following structure: [formula: see text] where Acyl = D-3
      hydroxylbutyryl, and 3-O-acetylation was approximately 30%.

PMID- 9658572
TI  - Structural analysis of the intact polysaccharide mannan from Saccharomyces
      cerevisiae yeast using 1H and 13C NMR spectroscopy at 750 MHz.
AB  - The mannan from Saccharomyces cerevisiae yeast was studied by high field NMR
      spectroscopy in an attempt to deduce the structure of the polysaccharide and to
      assess the ratio of different side chains. The results show that all structural
      information, agreeing with previously published data, can be extracted by
      analysis of the NMR spectra of the intact and modified mannan.

PMID- 9658573
TI  - Synthesis of phenoxyacetic acid derivatives as highly potent antagonists of
      gastrin/cholecystokinin-B receptors. II.
AB  - A series of phenoxyacetanilide derivatives was synthesized and their antagonist
      activities for human gastrin/cholecystokinin (CCK)-B and CCK-A receptors were
      evaluated. Among the compounds synthesized, 2-[3-[3-[N-[2-(N-methyl-N
      phenylcarbamoylmethoxy)phenyl]-N-(N-meth yl-N-
      phenylcarbamoylmethyl)carbamoylmethyl]-ureido]phenyl]acetic acid (20i, DA-3934)
      exhibited high affinity for gastrin/CCK-B receptors and high selectivity over CCK
      A receptors. DA-3934 and its methyl ester derivative inhibited pentagastrin
      induced gastric acid secretion in rats in a dose-dependent manner.

PMID- 9658574
TI  - alpha-Methylene-gamma-butyrolactones: synthesis and vasorelaxing activity assay
      of coumarin, naphthalene, and quinoline derivatives.
AB  - Certain alpha-methylene-gamma-butyrolactone derivatives of coumarin, naphthalene,
      and quinoline were synthesized and evaluated for vasorelaxing effects on isolated
      rat thoracic aorta. The 7-[(2,3,4,5-tetrahydro-2-methyl-4-methylene-5-oxo-2
      furanyl)methoxy]-2H- 1- benzopyran-2-ones, which have an aliphatic methyl
      substituent at the lactone C2, were more active than their C2-phenyl counterparts
      against high-K+ (80 mM) medium, Ca2+ (1.9 mM)-induced vasoconstriction and the
      norepinephrine (NE, 3 microM)-induced phasic and tonic constrictions (2a vs. 2b;
      2c vs. 2d; 2e vs. 2f; 2g vs. 2h). Although 3-chloro-7-[(2,3,4,5-tetrahydro-2
      methyl-4-methylene-5-oxo-2- furanyl)methoxy]-4-methyl-2H-1-benzopyran-2-one (2g)
      demonstrated the most potent inhibitory activities on the NE-induced phasic and
      tonic constrictions at concentrations of as low as 10 micrograms/ml, it possesses
      both affinity for NE-receptor and intrinsic activity to trigger the
      vasoconstriction. However, 8-[(2,3,4,5-tetrahydro-2-methyl-4-methylene-5-oxo-2-
      furanyl)methoxy]quinoline (10a) and other quinoline derivatives (11a, 12a) are
      pure irreversible non-competitive blockers of NE-receptor with no intrinsic
      activity. The aromatic ring played an important role in the vasorelaxing effects
      of alpha-methylene-gamma-butyrolactones; naphthalene was inactive, quinolines
      exhibited only affinity to the alpha-receptor, and coumarins possessed both
      affinity and intrinsic activity.

PMID- 9658575
TI  - Studies on 5-lipoxygenase inhibitors. I. Synthesis and 5-lipoxygenase-inhibitory
      activity of novel hydroxamic acid derivatives.
AB  - A series of novel hydroxamates has been prepared and tested for inhibitory
      activity towards rat polymorphonuclear leukocyte (PMN) 5-lipoxygenase (5-LO) in
      vitro and towards neutrophil migration in the rat air pouch model of inflammation
      in vivo. Many 3,4-dihydronaphthyl compounds were potent inhibitors of 5-LO, and
      several compounds were potent inhibitors of neutrophil migration. The most potent
      3,4-dihydronaphthyl compound, N-[[(3,4-dihydro-5-phenoxy)-2-naphthyl]methyl]-N
      hydroxy-N'-ethylurea (FR122788, 18) had an IC50 of 25 nM in the 5-LO assay, and
      strongly reduced neutrophil migration in the rat air pouch model at 1 mg/kg
      (p.o.). FR122788 also had an ameliorating effect in a rat hepatitis model induced
      by D-galactosamine, with an ED50 values of 14.6 mg/kg (p.o.) for glutamate
      oxaloacetate transaminase (GOT) and 16.8 mg/kg (p.o.) for glutamate pyruvate
      transaminase (GPT).

PMID- 9658576
TI  - Studies on nonpeptide angiotensin II receptor antagonists. IV. Synthesis and
      biological evaluation of 4-acrylamide-1H-imidazole derivatives.
AB  - A novel series of nonpeptide angiotensin II antagonists containing the acrylamide
      group at the 4-position of the imidazole ring was synthesized and their
      antagonistic activity was examined by functional assay in rabbit aorta. The
      acrylamide group was selected as a large lipophilic surrogate for the chloro
      group of EXP3174. A structure-activity relationship study of the acrylamide
      moiety has shown that substitution at the 4-position with the N-methyl-3,3
      dimethylacrylamide group resulted in the optimal compound, 2-butyl-4-[(3,3
      dimethylacryloyl)methyl-amino]-1-[[2'-(1H-tetra zol-5- yl)biphenyl-4-yl]methyl]
      1H-imidazole-5-carboxylic acid (1), which was superior to EXP3174 in vitro. Since
      1 showed only poor activity against angiotensin II-induced pressor response in
      rats after oral administration, the carboxylic acid function of 1 was converted
      into prodrug esters (13). Among these, the 1-[(ethoxycarbonyl)oxy]ethyl ester
      (13a) showed the most potent and longest-lasting activity when given orally to
      rats. When administered orally to conscious furosemide-treated dogs, 13a showed
      an approximately 3-fold increased hypotensive activity in comparison with DuP
      753. These data suggest that 13a may be an useful agent for the treatment of
      angiotensin II-dependent diseases, such as hypertension.

PMID- 9658577
TI  - Medicinal foodstuffs. XIV. On the bioactive constituents of moroheiya. (2): New
      fatty acids, corchorifatty acids A, B, C, D, E, and F, from the leaves of
      Corchorus olitorius L. (Tiliaceae): structures and inhibitory effect on NO
      production in mouse peritoneal macrophages.
AB  - Following the characterization of the glycosidic constituents in a medical
      foodstuff "moroheiya," the leaves of Corchorus olitorius L., four higher fatty
      acids with a trienone function, corchorifatty acids, A, B, C, and D, an
      undecanoic acid, corchorifatty acid E, and a trihydroxyfatty acid, corchorifatty
      acid F, were isolated from the less polar fraction of "moroheiya". The structures
      and optical purity of corchorifatty acids were determined on the basis of
      chemical and physicochemical evidence. Corchorifatty acids A, B, and C showed an
      inhibitory effect on lipopolysaccharide-induced NO production in cultured mouse
      peritoneal macrophages.

PMID- 9658578
TI  - Serotonin 5-HT4 receptor agonistic activity of the optical isomers of (+/-)-4
      amino-N-[2-(1-azabicyclo[3.3.0]octan-5-yl)ethyl]-5-chloro-2,3- dihydro-2
      methylbenzo[b]furan-7-carboxamide.
AB  - The enantiomers, (R)-(-)-1 and (S)-(+)-1, of (+/-)-4-amino-N-[2-(1
      azabicyclo[3.3.0]octan-5-yl)ethyl]-5-chloro-2,3- dihydro-2-methylbenzo[b]furan-7
      carboxamide [(+/-)-1] were prepared from optically active benzyl 4-acetylamino
      2,3-dihydro-2-methylbenzo[b]furan-7-carboxylate [(R)-(+)-6, (S)-(-)-6],
      respectively. The requisite (R)-(+)-6 and (S)-(-)-6 were prepared by large-scale
      preparative HPLC on chiral stationary phases (CSPs). The absolute configuration
      of (S)-(+)-1 was determined by single crystal X-ray analysis. The serotonin 5-HT4
      receptor agonistic activity of (S)-(-)-1 hemifumarate (SK-951) which was
      hemifumarate of (S)-(+)-1 was about twice that of the other enantiomer (R)-(+)-1
      hemifumarate which was hemifumarate of (R)-(-)-1.

PMID- 9658579
TI  - Studies on the constituents of Broussonetia species. III. Two new pyrrolidine
      alkaloids, broussonetines G and H, as inhibitors of glycosidase, from
      Broussonetia kazinoki Sieb.
AB  - Two new pyrrolidine alkaloids, broussonetines G and H, were isolated from the
      branches of Broussonetia kazinoki SIEB. (Moraceae). Broussonetines G and H were
      formulated as 2 beta-hydroxymethyl-3 alpha, 4 beta-dihydroxy-5 alpha-(1-hydroxy-
      6:10;10:13-diepoxytridecyl)-pyrrolidine (1) and 2 beta-hydroxymethyl-3 alpha, 4
      beta-dihydroxy-5 alpha-(1-hydroxy- 5:9;9:13-diepoxytridecyl)-pyrrolidine (2),
      respectively, by spectroscopic methods. 1 and 2 inhibited beta-glucosidase, beta
      galactosidase and beta-mannosidase.

PMID- 9658581
TI  - Receptor binding thermodynamics as a tool for linking drug efficacy and affinity.
AB  - Determination of drug-receptor binding constants (association, KA, or
      dissociation, KD = l/KA) by radiochemical specific binding assays has proved to
      be an invaluable tool for screening of potential active drugs. Simple
      determination of KA (or KD) values makes it possible, however, to calculate the
      standard free energy delta G degree = -RTln KA = RTln KD (T = 298.15 K) of the
      binding equilibrium but not that of its two components as defined by the Gibbs
      equation delta G degree = delta H degree - T delta S degree, where delta H degree
      and delta S degree are the equilibrium standard enthalpy and entropy,
      respectively. This incomplete knowledge is highly inconvenient from a pure
      thermodynamic point of view as delta H degree and delta S degree carry much
      information on the details of the drug-receptor interaction and the interplay of
      both reaction partners with the solvent. In recent times it has been shown that
      the relative delta H degree and delta S degree magnitudes can often give a simple
      'in vitro' way for discriminating 'the effect', that is the manner in which the
      drug interferes with the signal transduction pathways. This particular effect,
      called 'thermodynamic discrimination', results from the fact that binding of
      antagonists may be enthalpy-driven and that of agonists entropy-driven, or vice
      versa. The first case of thermodynamic discrimination was reported for the beta
      adrenergic G-protein coupled receptor (GPCR) and only recently has it been
      confirmed for adenosine A1 and A2a receptors. Only very recently has the binding
      thermodynamics of ligand-gated ion channel receptors (LGICR) been investigated
      and data for four receptors have been reported showing that all of them are
      thermodynamically discriminated. While it seems difficult at present to find a
      reasonable explanation for the thermodynamic discrimination phenomenon in GPCR,
      some hypotheses can be suggested for LGICR. Since global delta H degree and delta
      S degree values of the binding process are expected to be heavily affected by
      rearrangements occurring in the solvent, thermodynamic discrimination in LGICR is
      at least logically understandable admitting that the observed delta H degree (and
      then delta S degree) values are determined by both specific binding and abrupt
      variation of water-accessible receptor surfaces consequent to the setting up of
      the channel opening.

PMID- 9658582
TI  - Modulation of glutamate receptor pathways in the search for new neuroprotective
      agents.
AB  - Excessive stimulation of excitatory amino acid (EAA) receptors is responsible for
      a wide variety of acute and chronic neurological impairments. A separate line of
      investigation has focused on oxidative stress as one of the main reasons for
      several of these degenerative disorders. Current evidence has confirmed that
      activation of both ionotropic and metabotropic glutamate receptors can also
      result in either neuroprotection or neurodegeneration according to the role
      played by oxidative stress mechanisms. An outline of this research, together with
      our recent results aimed at the discovery of new subtype selective modulators of
      the central nervous system pathways as well as new classes of free radical
      scavengers, is presented.

PMID- 9658583
TI  - Obesity genes: molecular genetic approaches to drug target identification.
AB  - The environment for developing novel therapeutic agents has undergone dramatic
      change over the past decade. Innovative strategies for identifying and utilizing
      molecular targets linked to particular human diseases are replacing the classic
      approach of screening chemical compounds for potential therapeutic action on
      unknown targets. Since genetic components are involved in many known diseases,
      mouse and human genetics, positional cloning and other molecular biology-based
      approaches are now used to identify genes that are associated with these
      diseases. It is thought that identification of these disease-linked genes may
      lead to the discovery and understanding of the physiologically relevant
      biochemical pathways underlying the disease processes. Clearly, a knowledge of
      these biochemical pathways will provide future molecular targets, enzymes or
      receptors, that will offer opportunities to apply modern methods of high
      throughput screening, medicinal chemistry, parallel synthesis and combinatorial
      chemistry for drug discovery. In this manuscript, we illustrate how mouse
      genetics and molecular biology-based approaches have led to the identification of
      all five known single gene mutations that cause obesity in mice. Additionally, we
      describe how identification of these genes has helped unravel underlying
      biochemical pathways that regulate behavioral, metabolic and neuroendocrine
      responses in rodents.

PMID- 9658584
TI  - Csk-mediated phosphorylation of substrates is regulated by substrate tyrosine
      phosphorylation.
AB  - Csk is a cellular protein tyrosine kinase (PTK) that has been shown to
      specifically regulate the activity of Src kinase family members by
      phosphorylation of a carboxy-terminal tyrosine residue. The molecular mechanisms
      controlling Csk regulation and its substrate specificity have not been
      elucidated. Here we report a novel type of overlay kinase assay that allows to
      probe for Csk-mediated phosphorylation of cellular substrates separated by
      polyacrylamide gel electrophoresis and transferred to nitrocellulose filters.
      Most of the cell lines analyzed with this method revealed only a few potential
      Csk substrates. However, an increased number of Csk substrates was detected in
      NIH3T3 cells expressing a constitutively activated form of the Src kinase Lck or
      in PC12 and NIH3T3 cells that had been treated with pervanadate. These cells all
      display an increased level of cellular protein tyrosine phosphorylation which led
      to the conclusion that Csk preferentially phosphorylates tyrosine-phosphorylated
      proteins. To verify this hypothesis we analyzed Csk-mediated phosphorylation of
      recombinant Lck, a known Csk substrate. Results demonstrated that
      autophosphorylation of Lck (at Tyr394) facilitates Csk-mediated phosphorylation
      of Lck at its regulatory site (Tyr505). Subsequent peptide binding studies
      revealed that Csk can bind to a peptide corresponding to the Lck
      autophosphorylation site only when it is phosphorylated. These findings suggest
      that autophosphorylation of Lck at Tyr394 triggers an interaction with Csk and
      thereby facilitates subsequent phosphorylation and inactivation of Lck. The
      phosphorylation of other cellular Csk substrates may be regulated by a similar
      mechanism.

PMID- 9658585
TI  - Molecular mechanisms involved in the activation and regulation of the alpha 1
      adrenergic receptor subtypes.
AB  - The adrenergic receptors (ARs) belong to the superfamily of membrane-bound G
      protein coupled receptors (GPCRs). Our investigation has focused on the structure
      function relationship of the alpha 1b-AR subtype used as the model system for
      other GPCRs. Site-directed mutagenesis studies have elucidated the structural
      domains of the alpha 1b-AR involved in ligand binding, G protein coupling or
      desensitization. In addition, a combined approach using site-directed mutagenesis
      and molecular dynamics analysis of the alpha 1b-AR has provided information about
      the potential mechanisms underlying the activation process of the receptor, i.e.
      its transition from the 'inactive' to the 'active' conformation.

PMID- 9658586
TI  - Search for selective antagonists at alpha 1-adrenoreceptors: neutral or negative
      antagonism?
AB  - In this article the use of competitive antagonists as tools in receptor
      characterization and classification is discussed. It is pointed out that caution
      is required in receptor characterization because negative antagonism (inverse
      agonism) rather than neutral antagonism could play a relevant role. This implies
      that antagonists should be evaluated not only with regard to their affinity, but
      also with regard to their ability to affect the equilibrium between the two
      receptor states, namely active and inactive states. Since affinity and efficacy
      of a negative antagonist are system dependent the use of negative antagonists as
      competitive antagonists in receptor characterization may give rise to false
      differences in receptor subtypes. Finally, this article summarizes recent
      developments in the design of new alpha 1-adrenoreceptor antagonists which are
      structurally related to prazosin or WB 4101.

PMID- 9658587
TI  - Molecular toxicology and the medicinal chemist.
AB  - Drug metabolism has a number of pharmacodynamic and pharmacokinetic consequences
      which cannot be ignored even at the early stages of drug research. A number of
      aspects of drug metabolism are thus of interest to medicinal chemists, e.g.
      prodrug and soft drug design. This mini-review focuses mainly on toxication
      resulting from reactions of functionalization and conjugation. In the former
      case, oxidoreductases can reduce xenobiotics to nucleophilic radicals, or oxidize
      them to electrophilic and oxidizable metabolites. Conjugation reactions also play
      a role in toxication by generating lipophilic residues (e.g. hybrid
      triglycerides) or adduct-forming metabolites (e.g. some acylglucuronides), or by
      interfering with physiological pathways (e.g. Coenzyme A conjugates). Functional
      moieties undergoing such reactions are known as toxophoric groups. Because they
      are the biochemical endpoint of several toxication reactions, macromolecular
      adducts are now of special significance in molecular toxicology. But, as
      discussed in the conclusion, the substrate specificity of drug-metabolizing
      enzymes, the many biological factors that influence metabolism, and various
      repair and removal mechanisms all contribute to decrease toxicological risks and
      to protect organisms.

PMID- 9658588
TI  - Synthesis and antihypertensive activity of 2,4-dioxoimidazolidin-1-yl and
      perhydro-2,4-dioxopyrimidin-1-yl ergoline derivatives.
AB  - The synthesis and antihypertensive activity of a series of 2,4-dioxoimidazolidin
      1-yl and perhydro-2,4-dioxopyrimidin-1-yl ergoline derivatives are reported. The
      oral antihypertensive activity was studied in spontaneously hypertensive rats
      (SHRs) by measuring systolic blood pressure by an indirect tail-cuff method at
      different times after treatment. The prolactin lowering activity (indirectly
      measured by the nidation test) in rats and the oral acute toxicity in mice were
      also studied. The results of this study revealed potent antihypertensive ergoline
      derivatives devoid of side-effects related to the dopaminergic stimulation and
      the importance of the delta 9,10 double bond for conferring high potency within
      these compounds.

PMID- 9658589
TI  - 1,2,3-Triazolo[1,5-a][1,4]- and 1,2,3-triazolo[1,5-a]-[1,5]benzodiazepine
      derivatives: synthesis and benzodiazepine receptor binding.
AB  - This paper reports the synthesis of new 1,2,3-triazolo[1,4]benzodiazepine and
      1,2,3-triazolo[1,5]benzodiazepine derivatives and their evaluation toward
      benzodiazepine receptors. Receptor affinity gradually and remarkably increases by
      moving the nitrogen atom of the central ring from position 3 through 4 to
      position 5, to give the most effective compound 6a (Ki = 150 nM). N-methylation
      of the diazepine ring (7a) lowers receptorial binding. Introduction of a chlorine
      atom on the benzene ring doubles the Ki value (6b) which remains unaltered by the
      N-methylation (7b).

PMID- 9658590
TI  - Comparison of three histological fixatives on the immunoreactivity of mammalian P
      glycoprotein antibodies in the sheepshead minnow, Cyprinodon variegatus.
AB  - Mammalian P-glycoprotein is a highly conserved integral membrane protein
      functioning as an energy-dependent efflux pump which decreases the concentration
      of certain lipophilic aromatic compounds entering the cell by diffusion.
      Expression of such a transporter in teleost species could play a significant role
      in conferring resistance to fish populations exposed to xenobiotic stressors and
      may serve as a potential indicator of species at risk for certain environmental
      contaminants. In previous studies we demonstrated that a strong correlation
      existed between corresponding mammalian and teleost tissues showing
      immunoreactivity to specific mammalian P-glycoprotein antibodies. In the present
      study, comparisons of staining pattern, intensity, and tissue specificity between
      tissues treated in Bouin's, Dietrich's and Lillie's histological fixatives were
      determined in the sheepshead minnow, Cyprinodon variegatus, using monoclonal
      antibodies C219, C494, JSB-1 and polyclonal antiserum MDR(Ab-1). Immunoreactivity
      of these antibodies was found to be fixative-dependent. Results are presented
      illustrating the differential staining patterns and tissue specificity observed
      for each tissue type, fixative, and antibody combination. Our data indicate
      tissue fixation has a significant impact on P-glycoprotein antibody immuno
      reactivity in teleost tissues and must be considered in the comparison and
      interpretation of results.

PMID- 9658591
TI  - Kinematics of aquatic and terrestrial prey capture in Terrapene carolina, with
      implications for the evolution of feeding in cryptodire turtles.
AB  - Studies of aquatic prey capture in vertebrates have demonstrated remarkable
      convergence in kinematics between diverse vertebrate taxa. When feeding in water,
      most vertebrates employ large-amplitude hyoid depression to expand the oral
      cavity and suck in water along with the prey. In contrast, vertebrates feeding on
      land exhibit little or no hyoid depression. In this study we compared the
      kinematics of terrestrial and aquatic prey capture within one species of turtle,
      Terrapene carolina, in order to determine whether an individual species can
      modulate the magnitude of hyoid depression between air and water. High-speed
      video (250 frames per second) showed that hyoid depression was over three times
      greater in aquatic than in terrestrial feedings, indicating that T. carolina is
      able to modulate hyoid depression magnitude depending on the medium in which
      feeding occurs. In addition, we observed medium-dependent modulation of hyoid
      depression in another turtle, Heosemys grandis, and large-amplitude hyoid
      depression during aquatic feeding in Kinosternon leucostomum, Platysternon
      megacephalum, and juvenile Chelydra serpentina. In all of these turtles, hyoid
      depression produced oral cavity expansion during aquatic feeding, but the
      earthworm prey were never sucked toward the predators. Prey were captured by neck
      extension (ram feeding), and we conclude that the function of hyoid depression
      during aquatic feeding in cryptodire turtles is to prevent the forward motion of
      the predator from pushing the prey away (compensatory suction). Aquatic feeding
      is probably the primitive condition for all extant turtles, and thus terrestrial
      feeding in T. carolina and other turtles is a secondarily derived characteristic.
      We conclude from this historical pattern that it is not appropriate to use extant
      turtles in attempts to reconstruct the terrestrial feeding mechanisms of
      primitive amniotes.

PMID- 9658592
TI  - Cellular mechanisms of intestine regeneration in the sea cucumber, Holothuria
      glaberrima Selenka (Holothuroidea:Echinodermata).
AB  - Echinoderms are the deuterostome group with the most striking capacity to
      regenerate lost body parts. In particular, members of the class Holothuroidea are
      able to regenerate most of their internal organs following a typical evisceration
      process. Such formation of new viscera in an adult organism provides a unique
      model to study the process of organogenesis. We have studied this process in the
      sea cucumber Holothuria glabberrima by describing the spatial and temporal
      pattern of cellular events that occur during intestine regeneration following
      chemically induced evisceration. Regeneration begins as a thickening of the
      mesenteries that supported the autotomized organs to the body wall. The
      mesenterial thickening consists of tissues where most of the cellular populations
      found in the normal intestine are already present. However, the cell numbers
      differ, particularly those of hemocytes and amoebocytes, suggesting that some of
      these cells play an important role in the formation of the solid rod of
      hypertrophic mesentery that characterizes the intestinal primordia. The
      appearance of the luminal epithelium, together with the formation of the lumen,
      occurs during the second week of regeneration by proliferation and extensive
      migration of cells from the esophagus and cloacal ends into the thickenings. At
      this stage all tissue layers are present, but it takes an additional week for
      them to exhibit the proportions typical of the normal organ. Cell division, as
      determined by BrdU labeling, mainly occurs in the coelomic epithelia of the
      hypertrophic mesentery and in the regenerating luminal epithelium. Our study
      provides evidence that the process of new organ formation in holothurians can be
      described as an intermediate process showing characteristics of both epimorphic
      and morphallactic phenomena.

PMID- 9658593
TI  - Gradient in convergent cell movement during Fundulus gastrulation.
AB  - This contribution represents a continuation of our studies of a gradient in
      convergent cell movement in the germ ring (GR) during Fundulus gastrulation
      (Trinkaus et al. [1992] J. Exp. Zool., 261:40-61). In our previous study, we
      discovered that cells in the dorsal GR nearest the embryonic shield (ES) move
      toward the ES at a net faster rate than those farther away and that this is due
      to less meandering. Those farther away meander more. These data suggest the
      hypothesis that there is a gradient of cues that direct cells to the ES. If so,
      cells in the ventral GR, farthest from the ES, should meander even more and hence
      show little or no convergence toward the ES. To test this hypothesis, we have
      traced the trajectories of individual cells in the midventral GR during
      midepiboly and have found that, although the general motile behavior of ventral
      GR cells is the same as that of dorsal cells, they do indeed meander much more
      and, as a result, show little or no directional movement toward the ES. Taken
      together, these results indicate that cells of the germ ring move up a gradient
      in directionality as they converge toward their target, the embryonic shield. One
      possible explanation for this is that the embryonic shield attracts cells to
      itself.

PMID- 9658594
TI  - Hormonal and photoperiodic modulation of testicular mRNAs coding for
      inhibin/activin subunits and follistatin in Clethrionomys glareolus, Schreber.
AB  - Photoperiodic and hormonal modulation of mRNAs for testicular inhibin/activin
      subunits and follistatin were studied in a seasonally breeding rodent, the bank
      vole (Clethrionomys glareolus). Photoperiod-induced testicular regression had no
      effect on the relatively low steady-state levels of follistatin mRNA. Inhibin
      alpha (I alpha) and beta B (I beta B) mRNA levels were significantly higher in
      regressed than in active gonads, but inhibin beta A was undetectable. The effect
      of gonadotropin administration on testicular weight and mRNA concentrations
      differed between the sexually active and quiescent voles. Neither FSH (1.2 U/kg;
      s.c. for 5 days) nor hCG (600 IU/kg; s.c. for 5 days) affected testicular weight
      in sexually active voles, whereas both gonadotropins significantly increased
      testicular weight in photo-regressed individuals. FSH had no effect on I alpha or
      I beta B mRNA concentrations in the active testes, whereas excessive hCG
      challenge induced a decrease in the steady-state levels of these mRNAs. FSH
      induced an increase in I alpha mRNA concentrations in the regressed gonad,
      whereas both gonadotropins concomitantly down-regulated I beta B mRNA levels. In
      conclusion, the high expression of I alpha and I beta B mRNA in the regressed
      testis imply autocrine and paracrine roles for inhibin/activin in the quiescent
      gonad of seasonal breeders. Inhibin alpha-subunit expression is at least partly
      under the control of FSH in the bank vole testis.

PMID- 9658595
TI  - Differential sensitivity of zonagenesis and vitellogenesis in Atlantic salmon
      (Salmo salar L) to DDT pesticides.
AB  - In Atlantic salmon (Salmo salar L) female sexual maturation entails both
      zonagenesis and vitellogenesis, both of which are controlled by increasing levels
      of estradiol-17 beta (E2). Antibodies against salmon zona radiata proteins
      (eggshell zr-proteins) and vitellogenin were used to monitor induction of
      oogenesis in juvenile salmon. Molecular weights of zr-monomers were estimated to
      about 66, 61, and 55 kDa, and to about 180 kDa for vitellogenin. Xenobiotics such
      as the pesticide DDT impair biological reproduction. The o,p'-DDT (1,1,1
      trichloro-2[2-chlorophenyl]-2-[4-chlorophenyl]ethane) isomer seems to be a
      xenoestrogen. Serum levels of zr-proteins and vitellogenin, and hepatocytic
      biosynthesis of these components, were determined after in vivo treatment of
      salmon with DDT (technical, p,p'-(1,1,1-trichloro-2,2-bis[4-chlorophenyl]ethane)
      or o,p'-DDT) or E2. Exposing fish to frequent doses of o,p'-DDT (25 mg/kg b.w.
      (body weight) twice a week, six times totally) resulted in induction of all three
      zr-protein monomers, but not of vitellogenin. In contrast, three weekly injection
      of 10 mg/kg b.w. of either of the three DDT preparations did not induce typical
      zr-proteins or vitellogenin in serum. In vivo studies with combined DDT + E2
      injections showed that none of the DDT preparations influenced E2-induced
      biosynthesis of zr-proteins or vitellogenin. E2 induction of these oogenetic
      processes was not blocked even by a high concentration (125 mg/kg b.w.) of o,p'
      DDT. Furthermore, pretreatment of salmon with o,p'-DDT for 2 weeks, followed by
      one injection of E2, did not antagonize biosynthesis of zr-proteins, but serum
      concentration of vitellogenin was decreased. The data indicate that in juvenile
      salmon o,p'-DDT may be xenoestrogenic with regard to zonagenesis, but weakly anti
      (xeno)estrogenic with regard to vitellogenesis. These findings suggest new
      complexities in fish reproductive toxicology of xenoestrogens. Compared to
      vitellogenesis, zonagenesis is a more sensitive parameter for monitoring
      reproductive effects of xenoestrogens.

PMID- 9658596
TI  - Fulminant hepatic failure: is it a preventable syndrome?

PMID- 9658597
TI  - Ultrasound-guided puncture of the gallbladder for acute cholecystitis.
AB  - We performed a US-guided aspiration of the gallbladder in 27 patients with an
      acute cholecystitis and severe concurrent disease, not responding to IV
      antibiotics and supportive therapy. Twenty six of the 27 patients improved after
      the procedure. One patient died 7 days after the procedure due to multi organ
      failure; in the others immediate surgery could be avoided. Three patients
      experienced local pain after the procedure; no other puncture related
      complications were encountered. Long-term results (mean follow up 18 months;
      range 2-36 months) were excellent in 20/26 survivors with no biliary
      complications or need for elective cholecystectomy. Six of the 26 patients needed
      subsequent cholecystectomy for relapse or incomplete cure.

PMID- 9658598
TI  - Corticosteroid treatment in active Crohn's disease.
AB  - Despite recent improvements in the management of Crohn's disease, steroids are
      still the most efficacious treatment in flare ups of the disease. However they
      have significant side effects and are only effective in the short term. There is
      no consensus regarding initial dose or duration of corticotherapy. With 1 mg/Kg a
      day of oral prednisolone given for 3 to 7 weeks, 92% of the patients achieve
      clinical remission. Topical acting oral corticosteroids such as budesonide seem
      to represent an important therapeutic advance due to their better tolerance. The
      promising results of budesonide in mild and moderate flare ups need to be
      confirmed and its indication in severe disease beside high dose prednisolone has
      to be clarified.

PMID- 9658599
TI  - Ultrasonically guided fine needle puncture of focal liver lesions. Review and
      personal experience.
AB  - Despite recent advances in diagnostic imaging of the liver, the management of a
      patient with focal liver lesions often depends on obtaining tissue for
      histological diagnosis. Ultrasound guided fine needle biopsy is recommended as a
      safe and reliable method for cyto-histological confirmation of suspected hepatic
      malignancy. A fine needle is conventionally defined as having an outer diameter <
      or = 0.9 mm or > or = 19 G. Ultrasound guided fine needle aspiration cytology is
      found reliable for diagnosing malignancy. Limitations of this method are
      inadequate sampling and limited value in diagnosis of well-differentiated
      malignant tumours and benign tumours. Ultrasound guided fine needle cutting
      biopsy allows to obtain tissue for histological examination according to the
      Menghini technique. Both methods have high sensitivity, specificity and accuracy
      in detecting malignancy. In a personal series of 50 fine needle aspiration
      cytologies, a sensitivity for malignancy of 87% was obtained, with a specificity
      of 100%. The insufficient sampling rate, however, was 10%. Ultrasound guided fine
      needle trucut biopsy combines the advantages of a fine needle and a better
      sampling quality; a lower insufficient sampling rate can be expected without
      increase in complication rate. Despite the availability of numerous manually
      operated or (semi-) automated devices, little data have been published up to now
      on liver lesions. In our hands, it has proven to be a safe and reliable method,
      with low insufficient sampling rate, allowing correct identification of primary
      liver malignancies, correct suggestion of the primary source of the majority of
      metastases and correct identification of most benign liver lesions. Therefore it
      is considered as the method of choice when focal noncystic liver lesions are to
      be biopsied.

PMID- 9658600
TI  - Treatment of pancreatic pseudocysts by percutaneous drainage. Review and personal
      experience.
AB  - Pseudocysts are serious complications of acute and chronic pancreatitis.
      Asymptomatic pseudocysts require no specific treatment. Symptomatic pseudocysts
      can be decompressed by surgical, ultrasonographically and endoscopically guided
      methods. In the absence of randomised prospective trials it can not be stated
      that one of these technique is superior to others. Ultrasonographic and
      endoscopic approaches should be confined to centres with particular expertise in
      these techniques.

PMID- 9658601
TI  - Viral hepatitis throughout infancy to adulthood.

PMID- 9658602
TI  - Epidemiology of hepatitis B and C in Europe.

PMID- 9658603
TI  - Noncytolytic mechanisms involved in hepatitis B virus clearance.

PMID- 9658604
TI  - Hepatitis B virus mutants in HBsAg positive children.

PMID- 9658605
TI  - Genetic heterogeneity and properties of hepatitis C virus.
AB  - Hepatitis C virus (HCV) is a member of the Flaviviridae family. Its genome is a
      positive single-stranded RNA molecule which comprises three distinct regions: a
      5' non coding region, a long open reading frame encoding both the structural and
      non structural viral proteins, and a 3' non coding region. HCV circulates in
      infected individuals as complex mixtures of genetically distinct but closely
      related variants referred to as "quasispecies". The quasispecies nature of HCV
      genomes appears to play a major role in viral persistence, cell tropism of viral
      variants, pathogenicity and resistance to antiviral therapy.

PMID- 9658606
TI  - Mother-to-infant transmission of hepatitis C.

PMID- 9658607
TI  - Hepatitis C in children after transfusion: assessment by look-back studies.
AB  - Look-back studies to identify paediatric patients with post-transfusion hepatitis
      C have been conducted at several tertiary-care hospitals in Canada. A general
      look-back study was conducted at the Hospital for Sick Children in Toronto for
      the time period December 1985 to May 1990. All patients transfused at the
      Hospital for Sick Children during this time period were identified from hospital
      Blood Bank records. Letters of notification were sent by registered mail to all
      recipients excluding those known to have died. In the letter anti-HCV testing was
      recommended. Letters were mailed to 6332 transfusion recipients; 4496 letters
      were delivered. Of these 146 anti-HCV-positive transfusion recipients (92 pts <
      18 yrs old; 54 pts > 18 yrs old) were identified. Sixty-four of these patients
      were definitely transfused only during this time period. Assuming that all
      notified patients were tested, the minimum prevalence of new infection in this
      time period was 1.4%. When possible, identified patients were tested for presence
      of HCV RNA in the serum by RT-PCR. The proportion of patients anti-HCV positive
      but HCV RNA negative on one or more occasions was similar in both whole cohort
      and subset: approximately one-third. These data suggest that chronic hepatitis C
      may be less likely to develop after transfusion in children than in adults.

PMID- 9658608
TI  - Natural history of chronic viral hepatitis in childhood.
AB  - Chronic Hepatitis B virus (HBV) infection in children is commonly associated with
      Hepatitis B e antigen (HBeAg) seropositivity and histologic features of minimal
      to moderate hepatitis. Remission of liver disease is the rule following HBeAg to
      antiHBe seroconversion and clearance of HBV DNA from serum. In intermediate and
      low endemicity areas chronic HBV infection is usually acquired postnatally, and
      more than 80% of children are likely to achieve stable remission during the
      pediatric age. Severe sequelae, namely cirrhosis and HCC, have been observed only
      in less than 4% of children followed over two decades. In all cases cirrhosis was
      an early complication. Chronic HCV infection is usually silent in children. The
      chronicity rate seems to be high (50-80%) in post-transfusion hepatitis C as well
      as in perinatally acquired infection. HCV-associated liver disease is
      characterized by fluctuations of ALT which remain below two times the normal in
      about half of the cases. Liver histology shows minimal to mild hepatitis in the
      large majority of patients and cirrhosis is rare. Few patients achieve
      spontaneous remission and progression to a more severe liver disease might occur
      in adult life.

PMID- 9658609
TI  - Hepatitis B and C in eastern Europe--the current situation.

PMID- 9658610
TI  - Risk of hepatitis A superinfection in patients with underlying liver disease.
AB  - During recent years the outcome of acute hepatitis A in chronic liver disease has
      been discussed controversially. Data from large hepatitis A epidemics and
      surveillance data from the United States suggest a significantly higher risk of
      fatal outcome in patients with chronic hepatitis B. Patients with chronic active
      hepatitis or liver cirrhosis seem to be at highest risk, while HBsAg carriers may
      exhibit a benign course of the disease. Patients with chronic hepatitis C also
      seem to have a significantly higher risk of fulminant hepatic failure when
      superinfected with hepatitis A. The recently reported unsuspected coincidence of
      autoimmune markers with a fulminant course of hepatitis A in those patients needs
      to be confirmed. Vaccination against hepatitis A in patients with chronic liver
      disease has been shown to be safe and effective.

PMID- 9658611
TI  - Hepatitis B: long-term outcome and benefits from mass vaccination in children.
AB  - Hepatitis B viruses can cause chronic liver diseases in both children and adults.
      In hyperendemic areas, although most related complications occur during
      adulthood, nearly half of the primary infection in chronic hepatitis B virus
      carriers occurs in perinatal period through maternal transmission and the other
      half are from horizontal transmission mainly through intrafamilial spread or
      injection using unsterilized needles. Children with chronic hepatitis B virus
      infection are mostly asymptomatic. They are generally active and growing well
      with very rare exceptions. Even with acute exacerbation of liver function and
      active inflammation, jaundice or growth failure is uncommon. Mild histologic
      abnormalities in the liver begins early in life and may progress to severe liver
      impairment in later life. Severe liver damage, with bridging hepatic necrosis or
      fibrosis, or cirrhosis of the liver may occur, but is rare during childhood.
      Universal immunization program of hepatitis B virus has been proved to be
      effective in reducing hepatitis B carrier rate for more than 10 folds, and the
      incidence of hepatocellular carcinoma in children has also been reduced
      significantly.

PMID- 9658612
TI  - Is liver biopsy needed in children with chronic hepatitis?

PMID- 9658613
TI  - Hepatitis virus induced autoimmunity.

PMID- 9658614
TI  - Interferon: a meta-analysis of published studies in pediatric chronic hepatitis
      B.
AB  - Perinatally infected Asian children respond poorly to interferon (IFN) therapy.
      In contrast, IFN therapy seems to be more effective in Caucasian children who
      presumably acquired HBV infection later in life. We reviewed seven controlled
      studies of IFN treatment in children with chronic hepatitis B living in western
      countries (216 treated, and 200 untreated children). Before treatment all
      patients were HBeAg and HBV-DNA +ve, with a biopsy proven chronic hepatitis B.
      Ages ranged 1 to 16 years (mean age 7 years). Most patients were Caucasian.
      Protocols which have been adopted may schematically be divided into protocols
      which have used high doses of IFN (7.5 to 10 MU/sqm/TIW), and protocols which
      have used low doses of IFN (3 to 6 MU/sqm/TIW), with a short (3 to 6 months) or a
      long duration of treatment (12 months). The percentage of treated patients who,
      at the end of treatment, lost HBV-DNA (that in most studies corresponded also to
      HBeAg serum conversion) averages 20 to 58% (mean 35.5%) that is much higher than
      that observed in controls (range 8-17%; mean 11.4%). A better trend is probably
      observed only in patients who received the treatment for a longer period of time.
      At the end of treatment, low percentages of patients lost BsAg (range 0-4%; mean
      1.1%): again higher doses tend to be more effective than lower doses. In some
      studies IFN has been shown to significantly accelerate the termination of viral
      replication. Data on longer term outcome of IFN treatment in Caucasian children
      are scarce and confirm results obtained at short and at medium-term FU either in
      horizontally either in perinatally infected children. Results from few randomized
      controlled trials of interferon therapy with prednisone priming in Chinese and
      Caucasian children were comparable to results obtained without prednisone. In one
      study steroid priming did not potentiate the effect of IFN, however it existed a
      tendency of prednisone to improve HBeAg clearance in patients with normal
      aspartate aminotransferase, and alanine aminotransferase activity lesser than 100
      u/l. In most studies, factors positively influencing response rates of IFN
      treatment are represented by severe inflammation in the basal liver biopsy, high
      basal levels of serum transaminase, low basal levels of serum HBV-DNA. Vertical
      transmission may be considered a factor adversely affecting the response to IFN
      treatment both in Chinese and Caucasian population. In general in most controlled
      studies, the majority of responders have shown a significant reduction in hepatic
      inflammation and transaminase normalization. Children have a low risk of
      developing severe IFN-induced side effects. Adverse reactions and worsening of
      health-related quality of life were tolerable and did not seem to be a limiting
      factor for IFN therapy in young candidates.

PMID- 9658615
TI  - Therapy for chronic hepatitis B: nucleoside analogues in adult and pediatric
      patients.

PMID- 9658616
TI  - Immunotherapy of chronic hepatitis B by anti HBV vaccine.
AB  - Vaccine therapy is now used in various infectious diseases. The hepatitis B virus
      (HBV) leads to chronic infection in around 5% of patients with a high risk of
      chronic active hepatitis which may result in cirrhosis and hepatocellular
      carcinoma. The partial efficacy of antiviral therapies (40% of sustained
      inhibition of HBV replication), their cost, their possible side effects and the
      immune-mediated pathology of HBV infection explain the need of new immune
      therapies in treating HBV infection. Experimental and clinical evidences suggest
      the usefulness of vaccine therapy in HBV chronic infection. In a pilot and opened
      study, forty-six consecutive chronic HBsAg carriers with chronic hepatitis and
      detectable serum HBV DNA were given 3 standard injections of the GenHevac B
      vaccine at one month interval. Six months after the first injection, 12 patients
      (26.1%) had undetectable HBV DNA while 8 others showed significant decrease (more
      than 50%) in HBV DNA titers. Six of these 12 responders received a standard
      course of alpha-Interferon (5 MU thrice weekly subcutaneously for 4 months) and
      all six had still undetectable HBV replication at the end of follow-up. Among the
      34 non responders to vaccine, 20 were given alpha-interferon and 2 the
      monophosphate derivate of Vidarabine: 12 of these 22 patients stopped HBV
      replication and in all 12, vaccine therapy had induced a significant decrease of
      HBV replication before the antiviral treatment with a decrease of mean serum HBV
      DNA from 392 pg/ml before to 217 pg/ml after vaccine therapy. In an ongoing
      controlled study, using the same vaccine schedule, serum HBV DNA disappeared more
      frequently after 6 months, in patients who were given a preS2/S vaccine (7/35)
      than in patients who received a S vaccine (1/21) or no vaccine (1/32). In
      responders to vaccine, an induction of specific proliferative responses was
      observed and this may contribute to the potential efficacy of anti-HBV vaccine
      therapy. No side-effect or vaccine-induced escape-mutants occurred during the
      follow-up. In summary, serum HBV DNA disappeared in 28 of the 46 patients (60.9%)
      who were given vaccine therapy, with (64.2%) or without (55.6%) Interferon. These
      results are not different at 6 months and at the end of follow-up from those of
      43 HBsAg chronic carriers who were given only an antiviral treatment. Active
      immune therapy against HBV appears efficient and less expensive than antiviral
      therapies in stopping HBV replication. Such results need to be confirmed by the
      completed results of our controlled, randomized trial which is now conducted in
      our unit.

PMID- 9658617
TI  - "Receptor-ligand" based new strategy for treatment of patients with chronic
      hepatitis B.

PMID- 9658618
TI  - Treatment of pediatric hepatitis C: results and perspectives.

PMID- 9658619
TI  - Global status of HB immunization, 1998.

PMID- 9658621
TI  - Ethical aspects of pediatric therapeutic clinical trials.

PMID- 9658620
TI  - Interferon treatment for chronic hepatitis B or C infection: costs and
      effectiveness.
AB  - INTRODUCTION: With recognition that resources are limited, health care payers and
      policy makers have increasingly turned toward economic analyses to determine
      whether particular therapies are an efficient use of economic resources. Both
      chronic hepatitis B and C infections can progress to cirrhosis or hepatocellular
      carcinoma over time. Interferon treatment has been shown to eradicate viremia,
      but only does so in a proportion of treated patients. It has potential side
      effects, has no proven long-term benefit on complications and is relatively
      expensive. OBJECTIVE: To determine the cost-effectiveness of interferon treatment
      by estimating the lifelong economic and clinical outcomes associated with
      interferon therapy versus standard care for patients with either chronic
      hepatitis B or C infection. METHODS: Computer cohort Markov model simulation to
      project the lifelong impact of the loss of hepatitis B or C viremia resulting
      from interferon on cirrhosis, life expectancy, and costs. The natural history of
      hepatitis B and C was based on published studies. Efficacy estimates for the loss
      of viremia were based on meta-analysis of published data. Using a societal
      perspective, economic estimates were based on cost of care data for patients with
      hepatitis and from estimates regarding the frequency of health resource
      utilization provided by expert panels. RESULTS: For 20 year old patients with
      either hepatitis B e antigen positive chronic hepatitis or histologically mild
      chronic hepatitis C infection, interferon should be cost saving, extending life
      and reducing lifetime expenditures and morbidity. Life expectancy should increase
      by 4.8 to 3.1 years for patients with chronic hepatitis B or C, respectively.
      Lifetime costs should be reduced on average by $6,300 to $6,900 for each patient
      treated with interferon. CONCLUSION: Chronic infection with hepatitis B or C can
      result in liver failure and death. Although only effective in a proportion of
      treated patients, interferon for chronic hepatitis appears to be an efficient use
      of societal resources so that economic reasons should not limit its use.

PMID- 9658622
TI  - Treatment with lamivudine for non-immunocompromized patients with chronic
      hepatitis B.

PMID- 9658623
TI  - Treatment with terlipressin as a bridge to liver transplantation in a patient
      with hepatorenal syndrome.
AB  - Hepatorenal syndrome is a rapidly lethal complication of cirrhosis. The present
      case provides further evidence of the efficacy of terlipressin in this context
      even with concomitant treatment with propranolol. A 56 year old male with HBV
      related cirrhosis developed renal failure characteristic of hepatorenal syndrome.
      He was also taking propranolol for primary prophylaxis of variceal bleeding.
      Terlipressin 6 mg/day was administered during haemodialysis and after 1 week
      plasma creatinine dropped from 6.2 to 2.8 mg%. Daily urinary volume, plasma
      sodium and natriuresis dramatically increased during the treatment.
      Discontinuation of the treatment led to a rapid relapse of renal failure (plasma
      creatinine from 1.8 to 2.2 mg%) and the drug was readministered until a
      successful liver transplantation could be performed 1 month after the beginning
      of the treatment. The patient has now a near normal renal function 3 months after
      transplantation.

PMID- 9658624
TI  - [Evaluation of the cochlear aqueduct patency: comparison of 2 noninvasive
      techniques].
AB  - Variations in cephalo-rachidian fluid pressure can be transmitted to the middle
      ear through the cochlear aqueduct (CA). This gives us a non-invasive manner to
      evaluate any changes in fluid pressure by measuring middle ear impedance
      (impedancemetry). The present study compared two indirect methods for measuring
      intracranial pressure: a) impedancemetry during evoked jugulo-tympanic reflex
      (JTR) and b) study of the tympanic membrane (TM) fine motility using a MMS-10
      analyzer. The latter is a new procedure involving the indirect evaluation of the
      fluid pressure. In fact, when the CA is open the labyrinthine fluid pressure is
      transmitted to the oval window, the stapes platina and, finally, to the tympanic
      membrane where it can be measured with an MMS-10 unit. This equipment can measure
      nanoliter shifts in the TM. In particular, comparison between the clinostatic and
      orthostatic tympanic motility measurements enable one to establish whether the CA
      is patent or not. In the present study 15 subjects were examined using both a)
      impedancemetry during jugular compression and b) analysis of the TM shift using
      an MMS-10 unit. In 14 of the 15 cases there was good correlation between the data
      obtained using both methods: in all but one case it proved possible to record a
      JTR-induced variation in impedance whenever the MMS-10 indicated that the CA was
      open. The results suggest that, in clinical practice, the two methods can be used
      in parallel for non-invasive monitoring of variations in intracranial pressure in
      patients with neurological involvement. On the other hand, in the E.N.T. field
      these techniques could be used to study inner ear pathologies causing dynamic
      alterations of the endolabyrinth fluids (endolymphatic hydrops, labyrinthine
      fistula).

PMID- 9658625
TI  - [Changes in posture in whiplash evaluated by static posturography].
AB  - Analyzing vestibular-spinal reflex by recording changes in the pressure center
      over time, static posturography provides precise, repeatable information
      regarding a person's posture and subsequent postural strategy. Moreover, using
      the detected postural pattern, this can presage likely genesis of problems in
      equilibrium. The purpose of the present work was to evaluate posturographic
      findings in subjects with chronic or persistent whiplash (WL)-induced
      disequilibrium in order to determine any clear postural pattern able to indicate
      the likely genesis of the disorder. Fifty young subjects were selected for the
      study: 28 (6 females) affected with equilibrium problems resulting from WL-type
      cervical strain and 22 (5 females) normal, age compatible controls (C) (mean age
      of the groups: WL = 37 +/- 14.3; C = 32.4 +/- 6.7; p = n.s.). The results
      obtained were statistically processed with a personal computer and specific
      software (Windows-SPSS). In the analysis of the means (T-test and ANOVA analysis
      of variance) p < 0.05 was considered significant. In the WL group there was an
      increase in the antero-posterior axis oscillation frequency as compared to the
      control group. This is indicated by the FFTY parameter in tests performed both
      with eyes open and closed. Likewise, in both tests, there was a decrease in the
      LFS value, a parameter correlating length with surface. The surface was increased
      in the WL group as compared to group C although this increase was significant
      only when the test was performed with eyes closed. In addition, the average
      velocity and standard deviation of velocity increased in the WL group but this
      was only statistically significant when the eyes were open. The results obtained
      in the present study show that whiplash victims show an increase in antero
      posterior oscillation frequency at the pressure center, as found in the open and
      closed-eye tests. This suggests that in WL subjects there is an evident
      disturbance of the fine postural system, leading to an increase in the surface
      parameters, tracing length and a decrease in LFS function. The onset of this
      partial postural decompensation can be seen in: a) decrease in fine static
      postural control which is reflected in an increase in body surface oscillation;
      b) an increase in energy consumption to maintain orthostatism as revealed in the
      decreased LFS. In conclusion, it appears reasonable to assume that cervical
      proprioceptive alterations play a preeminent role in the genesis of whiplash
      induced chronic postural instability. This would result in an attempt to vary the
      physiology from an ankle to a hip strategy; incomplete manifestation of this new
      posture would cause the feeling of instability mentioned by the patients and
      documented by posturography.

PMID- 9658626
TI  - [The contralateral ear in acquired cholesteatoma in children and adults].
AB  - Contralateral ear pathologies are frequently found in patients suffering from
      acquired cholesteatoma. A retrospective study was performed on 85 pediatric
      patients and 105 adults surgically treated for acquired middle ear cholesteatoma.
      All the patients were checked and the otomicroscopic picture photographed and
      compared in an attempt to gain insight into the pathogenesis and clinical
      indications by comparing two samplings from different age groups. In both groups
      the frequency of pathological contralateral ear manifestations was higher than
      found in the normal population. Similar results were obtained in the two groups
      and indicate that the same mechanisms come into play in both ears, starting at
      infancy. The finding of a particularly common association between cholesteatoma
      and contralateral retraction pockets with sinus cholesteatoma or pars tensa in
      the pediatric group appears to confirm that tubal dysfunction plays a pathogenic
      role in the genesis of cholesteatoma. From the practical point of view,
      systematic preventative measurement of the contralateral ear can lead to a
      reduction in major surgery and can affect the choice between open or closed
      tympanoplasty. Moreover, it may also condition the precision and length of the
      follow-up.

PMID- 9658627
TI  - [Surgical treatment of otosclerosis in the aged. Results of retrospective
      analysis].
AB  - Otosclerosis is, per se, a disease which rarely occurs after the age of 50. This
      is why stapes surgery is seldom performed in advanced age and there are few
      reports on the topic in the literature. The authors have performed a
      retrospective analysis of patients over the age of 65 who had undergone surgery
      for otosclerosis in the last 27 years. Out of a total of 3585 surgical
      procedures, 106 patients were analyzed. Most of the cases were in the advanced
      stages. Assessment of the outcome included pre- and post-operative audiometry,
      one year after surgery. Inner ear performance was established by evaluating air
      and bone conduction at 0.5, 1, 2, 3 and 4 kHz. The results showed that performing
      otosclerosis surgery is worthwhile even in the elderly with mixed auditory
      impairment, as long as the air-bone gap is limited to 20-30 dB and the surgical
      procedure is through. In this light, stapedotomy appears to be the most adequate
      technique. When evaluating the results the possibility of adopting a less
      powerful hearing aid should also be considered a success.

PMID- 9658628
TI  - [CO2 laser treatment in laryngeal papillomatosis].
AB  - Laryngeal papillomatosis is a rare, unpredictable pathology which often recurs.
      Although several forms of surgery have been suggested for this pathology, CO2
      laser surgery is the treatment of choice. This paper presents 30 cases of
      laryngeal papillomatosis, 12 of which arose in infancy, all treated by dissection
      and/or CO2 laser vaporization. The treatments were performed in one or more
      stages depending on the site and appearance of the lesions. Special care must be
      taken to preserve the anatomical integrity when a papillomatosis must be removed
      from the glottic area. The average number of surgical procedures per patient
      proved greater in multifocal vs. unifocal forms (4.7 vs. 1.6) and in children vs.
      adults (4.9 vs. 3.7). In four patients the pathology followed a neoplastic
      evolution. Today 57% of the subjects treated (17) are in clinical remission after
      an average 17 month follow-up. CO2 laser endoscopic microsurgery is presently the
      most suitable method for treating laryngeal papillomatosis although the
      biological features of this diseases often make treatment difficult.

PMID- 9658629
TI  - [Otoneurological manifestations in Fhar's disease. A case report].
AB  - Fhar's disease is a rare idiopathic CNS pathology characterized by widespread
      calcifications of the basal ganglia, cerebellar nuclei and endocranial vessels.
      The origin of this disease is unknown and a lack of thyroid and parathyroid
      pathologies is the main statement. From the clinical point of view,
      extrapyramidal manifestations are common while vertigo and equilibrium disorders
      are rare. In the present case vertigo and disequilibrium were the main symptoms.
      Fhar's disease was diagnosed by CT and MRI showing calcification of the basal
      ganglia without any metabolism disorders or thyroid and parathyroid pathology. A
      battery of neurotological tests showed alterations of VOR and ocular movement. In
      particular the saccades movements showed significant hypometria while the smooth
      pursuit showed gain diminution and corrective saccades. These anomalies imply
      dysfunction of sub-cortical centers regulating and modulating ocular movement.
      VOR alterations included both qualitative anomalies of nystagmus (i.e.
      dysrhythmia, square waves) and quantitative alterations (i.e. bilateral deficit
      response to caloric and rotatory stimuli). These alterations could be due to the
      impairment of cerebellum-vestibular and vestibular-thalamic pathways. Acoustic
      evoked potentials (ABR, MLR) ruled out central acoustic pathway dysfunction.

PMID- 9658630
TI  - [3 cases of post-stapedectomy labyrinthine fistula].
AB  - Three cases are presented of labyrinthine fistula which suddenly arose in
      patients who had undergone stapedectomy interposing a vein graft from the back of
      the hand. These patients had all enjoyed 12-15 years apparently problem free
      period before the fistula occurred. In all three cases the fistula was
      accompanied by objective dizziness and varying degrees of sensorineural or mixed
      hearing loss. The patients underwent revision surgery which identified the
      fistula and the endolymph oozing out of the graft from the previously installed
      prosthesis. The authors present the cases, describe how the symptoms arose and
      the results obtained with revision surgery. Finally, they discuss the need to
      first perform stapedotomy with a platinar hole; they indicate that the number of
      cases of total or partial stapedectomy should be limited only to those cases
      characterized by anatomical variations and/or whenever complications arise during
      surgery.

PMID- 9658631
TI  - [Malignant pilomatrixoma of the face].
AB  - The authors report a case of malignant pilomatricoma of the right preauricular
      region in a 66 year old woman. This is a rare neoplasm and only 36 cases have
      been reported in the literature: 10 in the cervical-facial region and 15 of the
      scalp. There are problems in differential diagnosis with benign pilomatricoma,
      basal cell carcinoma, squamous cell carcinoma, parotid masses and the initial
      stages of cutaneous and subcutaneous cysts. Diagnosis of malignant pilomatricoma
      is essentially histological. It has a low degree of malignancy but tends to recur
      after surgery and to metastasize even leading to death. Treatment of choice is a
      broad surgical excision followed by periodic check-ups. Such exeresis was
      performed in the case presented and the patient is alive and in good health 67
      months after surgery.

PMID- 9658632
TI  - [Ancient theories on the genesis of allergic rhinopathy. From the beginnings to
      the 18th century].

PMID- 9658633
TI  - [Lateral approaches to the clivus].
AB  - Thanks to ongoing development in microsurgical techniques to treat the skull base
      some clivus lesions, considered inoperable until a few years ago, can now be
      removed with relatively low mortality and morbidity. The approaches available for
      the treatment of lesions in this anatomical area can be broken down into anterior
      and lateral. The latter offer the surgeon several important advantages such as
      better control over the main vascular structures and the possibility of opening
      the intradural space without coming into communication with the pharynx. By
      virtue of their extreme versatility, the lateral approaches may be used in
      combination in a single operation or can be performed as staged procedures. Each
      of the lateral routes, however, has its own advantages and drawbacks. These are
      presented during a brief description of each technique. The main factor in
      selection of approach is the anatomical limits of the approach itself. Generally
      speaking, the largest surgical field is offered by the most destructive
      approaches. Although they do cause such deficits as unilateral hearing loss,
      these approaches permit greatly improved control over the vital structures.
      Nevertheless, when such deficits exist prior to surgery, the morbidity of such
      approaches is negligible. The histological nature of the disease, the variable
      relationships with the dura, the main neurovascular structures and other factors
      should all be considered when deciding how to manage each case. The surgeon must,
      however, have the range of skills required to perform the diversity of approaches
      to the lateral skull base so as to provide the patient with the best possible
      care.

PMID- 9658634
TI  - [Titanium condylar abutment: the contribution of 3D computed tomography].
AB  - Various techniques have been described in the treatment of recurrent TMJ
      dislocations amongst which, joint arresters form a prominent part. We describe a
      new type of bio-integrable joint stop, custom made with 3D-CT help, which
      alleviates the two main drawbacks of the technique: lack of retention through
      insufficient extension, and secondary mobilization of the stop. Two cases are
      reported, amounting to four stops with satisfactory two years follow-up.

PMID- 9658635
TI  - Blunt internal carotid artery trauma: report of two cases and review of the
      literature.
AB  - Blunt injury of the internal carotid artery (ICA) is a rare entity that should be
      considered by Maxillofacial surgeons in patients with facial fractures. Its
      recognition is often delayed because of the common association with other severe
      multi-system injuries. Early diagnosis is the key to successful management; the
      arteriography plays a confirmatory role on the diagnosis and determines whether
      surgical management of the injury is feasible. Therapeutic alternatives vary from
      one center to another; they include observation, conservative treatment,
      anticoagulation, ligation of the carotid artery with or without extracranial
      intracranial bypass, and arterial reconstruction.

PMID- 9658636
TI  - Prognosis value of the expression of Ki-67 for squamous cell carcinoma of the
      oral cavity.
AB  - Ki-67 is a nuclear antigen expressed in G1, S, G2 and M phase of cell cycle and
      absent in quiescent cells (G0). In some neoplasms, Ki-67 expression has a
      prognostic value. The purpose of this study was to determine the role of Ki-67
      expression like prognostic factor in oral squamous cell carcinoma (OSCC).
      Monoclonal antibody MIB-1 that recognizes Ki-67 antigen was used. 74 OSCCs were
      analyzed. 49% of OSCCs did not express Ki-67 antigen. In the Ki-67 positive
      tumours, the expression was slight in 36.5%, moderate in 10.8% and intense in
      10.8% of the cases. In all the positive OSCCs, the distribution of the marking
      was patchy in different zones of the tumour, moreover, in 65% of the lesions, the
      positive cells were located mainly in the proximity of intraoral blood vessels. A
      significantly more intense expression was noted on tumours that had not been
      differentiated (p < 0.05), with a larger nuclear pleomorphism (p < 0.05) and in
      lesions that invaded in the form of disassociated neoplastic cells of in small
      groups of neoplastic cells (p < 0.001). However, the expression of Ki-67 did not
      correlate with the mitosis count and it had no influence on survival.

PMID- 9658637
TI  - Remodelling of bilateral fractures of the mandibular condyle.
AB  - A case of complete remodelling of bilateral fractures of the mandibular condyle
      in an 11-year-old boy is presented. Initial radiographic examination revealed
      fractures of the right and left condylar neck with medial and anterior
      dislocation of the proximal fragment. The fractures were treated conservatively,
      with a short-time intermaxillary fixation and early jaw function, and thirty-five
      months later the patient was asymptomatic. Radiographic changes observed
      following treatment have revealed a gradual return to normal shape and position
      of the condyles.

PMID- 9658638
TI  - [Diagnostic and therapeutic methods in sleep apnea syndromes. The role of
      otorhinolaryngology].

PMID- 9658639
TI  - [Current treatment methods for osteosarcoma of the jaw bones].
AB  - It is also the most common primary malignant lesion of bone, excluding multiple
      myeloma. However it is rare: it occurs in 1 per 100,000 persons per year, and
      about 6% tot 7% of all osteosarcomas occur in the maxillofacial region. In this
      report, we discuss two cases of osteosarcoma in the maxillofacial region: one in
      the mandible and one in the maxilla. It is also a review of the literature. We
      discuss in detail the natural history of osteosarcoma in the jaw bones, the
      predisposing factors, the localisation, the presenting symptoms, the radiology
      and the methods of treatment.

PMID- 9658640
TI  - [New perspectives in the treatment of erectile dysfunction].

PMID- 9658641
TI  - [Current status of p53 tumor suppressor gene as a possible molecular marker of
      cancer of the prostate].
AB  - Diagnosis of prostate cancer has increased over the last few years both in
      localized and in more advanced stages. At present, several groups are working in
      the search and evaluation of alternative tumoral markers as the current ones do
      not cover all the Urologist's needs. In this context, a number of studies on the
      mutation of the tumour suppressor gen p53 in both localized and metastatic
      prostate cancer are being carried out. When a noxa acts on the DNA, protein p53
      inhibits the cell cycle allowing the repair systems to operate and, if the damage
      is significant enough, cell apoptosis. The loss of this control mechanism
      secondary to the synthesis of anomalous proteins can result in the proliferation
      of neoplastic cells. A revision of the most representative papers in the
      literature is presented here, addressing the surrounding controversy and the
      resulting future possibilities.

PMID- 9658642
TI  - [Treatment of erectile dysfunction using intracavernous pharmacotherapy].
AB  - Intracavernous injection of vasodilators has been the greatest diagnostic and
      therapeutical breakthrough in erectile dysfunction (E.D.). After 15 years
      experience, these vasodilators have demonstrated efficacy rates over 85%. This
      suggests that most cases of E.D. are the result of and inability of the smooth
      muscle to relax. This paper presents an overview of the diagnostic and
      therapeutic use of intracavernous vasodilating drugs. It includes an extensive
      review of the literature and our personal series with regard to efficacy,
      indications, contraindications and side-effects of these compounds. Alprostadil
      i.c. injection (PGE1) is an effective (> 70%) and safe treatment, and its use has
      been accompanied by an increased quality of life of patients, with very few side
      effects. Currently, PGE1 is a first choice drug in the treatment of impotence.
      When no response is seen, or pain develops after PGE1 administration, a number of
      vasoactive compounds associations can be used instead (phentolamine + PGE1,
      papaverine + phentolamine, and papaverine + phentolamine + PGE1). The
      phentolamine + VIP association has shown encouraging results. Prior to prescribe
      IC treatment with vasoactive drugs it is necessary to conduct a basic diagnostic
      study, and advise the patient. If treatment is finally accepted, the performance
      of adequate training and detailed medical follow-up is crucial.

PMID- 9658643
TI  - [Reconstructive surgery with polypropylene mesh associated with kidney
      transplant].
AB  - OBJECTIVE: There is very little literature on hernial complications of the
      abdominal wall in association to renal transplantation. The present report aims
      to evaluate their incidence and type, as well as the intervention carried out and
      its results. MATERIAL AND METHOD: A retrospective analysis of a series of 650
      renal transplantations has been carried out between 1978-1996 in our centre. A
      braided polypropylene mesh (Prolene) was used to repair abdominal wall defects
      and/or diagnosed hernias in 8 (1.2%) cases: 5 eventrations, 1 inguinal hernia and
      one combination of both: the last case required extensive debridement of the
      abdominal wall due to necrotizing fascitis. Mean time to eventration was 47.3
      months (range 1-106). RESULTS: In all cases, the mesh was placed in the pre
      peritoneal space. Two patients developed complications (one haematoma and one
      wound infection), though graft removal was not necessary in any case. Follow-up
      was 33.1 months (range 6-78) with no findings of hernial relapse. One patient
      started successful chronic ambulatory peritoneal dialysis (CAPD) 30 days after
      the intervention. CONCLUSIONS: The polypropylene mesh is a sound alternative in
      the treatment of hernial complications associated to renal transplantation, with
      acceptable morbidity, and efficacy rates that in our series reached 100%.

PMID- 9658644
TI  - [Analysis of our series of kidney transplants: urologic complications and
      survival].
AB  - PURPOSE: To review our series of 416 renal transplants, with special reference to
      the surgical complications and their management. METHODS: From June, 1986 to
      October 1997, we are performed 416 heterotopic renal transplants, harvested from
      cadavers. Reconstruction of the urinary tract reconstruction was by
      ureteroneocystostomy in practically all the cases. RESULTS: There were some
      urological complications in 80 patients (19.2%). The most common urological
      complication was obstruction of the urinary tract arising from stenosis (3.3%),
      lymphocele (4.3%) and clotting (1.2%). 78.1% of these urological complications
      were resolved by endourological techniques. Urinary fistula was observed in 12
      cases (2.8%). Vascular complications in 22 (6.9%), lithiasis in 5 (1.2%), and
      eventrations in 11 (2.6%). The treatment of these complications is described. The
      actuarial survival rates were 87.8% and 77.3% at one and five years respectively
      for the graft, and 92.4% and 83.5% for the patients. CONCLUSIONS: Our surgical
      complication rate in patients undergoing renal transplantation was 19.2%. The
      most common complication was urinary tract obstruction from stenosis (3.3%),
      lymphocele (4.3%) and clotting (1.6%); 78.1% of these obstructive complications
      were resolved by endourologic techniques. Percutaneous drainage and
      esclerotherapy of the lymphoceles resolved 66.6% of them. Renal biopsy performed
      with a 14G needle caused 5 severe hemorrhagic complications. There were no
      complications when an 18G needle was utilized.

PMID- 9658645
TI  - [Ambulatory treatment of ureteral lithiasis using shock wave extracorporeal
      lithotripsy].
AB  - Presentation of the results obtained with extracorporeal shock wave lithotripsy
      (ESWL) applied to 3173 ureteral lithiasis with a Dornier HM-4 equipment. Location
      of lithiasis was pyeloureteral junction (329), lumbar ureter (1068), sacral
      ureter (238), iliopelvic ureter (1474) and "lithiasic path" (64). All lithiasis
      were treated in situ. Treatments were carried out ambulatory with no anaesthesia.
      Treatment/lithiasis rate was 1.3. Percentage of stone-free patients with ESWL
      alone was 79.2% after the first session, and reached 86.14% with retreatment.
      Percentage of success for lithiasis in pyeloureteral junction was 81.8%, 79.7%
      for lumbar ureter lithiasis, 80.09% sacral lithiasis, 90.10% iliopelvic ureter
      lithiasis and 79.9% for those in the "lithiasic path". 12.6% lithiasis required
      post-ESWL auxiliary manoeuvres. Post-ESWL minor complications (pain, vegetations)
      occurred in 5.6% cases and major complications (obstruction, fever, sepsis) in
      2.9%. The factors influencing lithiasis fragmentation were the number of shock
      waves and the lithiasis duration. Size of lithiasis and presence or absence of
      ureteral catheter had no influence. These results suggest that ESWL is an
      effective method for managing ureteral lithiasis.

PMID- 9658646
TI  - [AIDS and HIV infections in urologic practice].
AB  - The infection caused by the Human Immunodeficiency Virus (HIV), a retrovirus,
      leads to a progressive decline and to the suppression of cell-mediated immunity
      favouring the development of opportunistic diseases and potentially fatal
      neoplasias which are practically innocuous in individuals with an intact
      immunologic system. The number of AIDS cases recorded in Spain until March 1997
      was 45,132, with a revised mortality rate of 58%. Cases in Murcia total 713 up to
      October 1997, of which 217 patients are being monitored in the AIDS Unit in our
      centre, 414 individuals have died in the region. It is well know that about one
      third of patients with diagnosed AIDS or who are HIV carriers will develop some
      type of genitourinary lesion, either as a result of a renal disorder, concurrent
      or not with HIV, or any other condition directly related to the infection. This
      is a report on our Service's experience in the treatment of HIV patients with
      genitourinary symptoms that, in a total of 15 cases, required our intervention.
      Emphasis is placed on the incidence of nephrolithiasis secondary to therapy with
      protease inhibitors over the last few months following introduction of this new
      therapeutic tool, prostatitis due to salmonella, and inlaid cystitis among
      others.

PMID- 9658647
TI  - [Stenosis of the membranous bulbar urethra: our experience in termino-terminal
      urethroplasty].
AB  - Between May 1989 and August 1996, the Urology Service, Polyclinic of Vigo,
      performed 24 termino-terminal urethroplasties in patients with bulbar or
      membranous urethral stenosis, measuring 1 to 2.5 cm long. The most frequent
      etiologies were iatrogenic (9/24) and traumatic rupture (7/24). After a mean
      follow-up of 5.4 years (1 year minimum) the success rate was 80% (19/24) and 20%
      (5/24) for restenosis, which were resolved through a single procedure of
      endoscopic internal urethrotomy in 3 of the 5 cases.

PMID- 9658648
TI  - [Bilateral adrenal pheochromocytoma].
AB  - Presentation of one case of bilateral suprarenal pheochromocytoma as early
      clinical evidence of a type 2 MEN, which at the time of diagnosis was a bilateral
      lesion. The presentation form was a picture of shock with HBP. Labetalol i.v. was
      used for initial control and phenoxybenzamine in the pre-operative. Diagnosis was
      achieved by biochemical (metanephrine) and radiological (CAT) testing. The
      patient was managed with bilateral suprarenalectomy through a single, anterior
      incision and abdominal cavity examination. The investigation of the remaining
      conditions that conform this syndrome was continued and a familial routine study
      implemented.

PMID- 9658649
TI  - [High-flow priapism after perineal trauma].
AB  - We report on the case of a 19-year-old man with post-traumatic high-flow priapism
      that appeared after riding on a mountain bike. Laboratory test (cavernous blood
      gas measurement) and image studies (color flow Doppler ultrasound and
      arteriography of the internal pudendal artery) that confirmed the diagnosis are
      depicted. He was successfully treated with selective percutaneous arterial
      embolization with autologous blood clot, recovering a normal erectile function.

PMID- 9658650
TI  - [Wunderlich syndrome caused by the rupture of a simple cyst in a patient treated
      with acetyl salicylic acid].
AB  - Report case of a Wunderlich syndrome due to spontaneous rupture of a simple renal
      cyst. The patient is a 77-year old, hypertensive female who was on routine
      treatment with Aspirin. The rarity of retroperitoneal haemorrhage with this
      origin is documented; also the influence of aspirin as predisposing factor for
      this condition is ruled out. Brief evaluation of the various diagnostic means
      available. An accurate evaluation that may allow to adopt a conservative aptitude
      is recommended.

PMID- 9658651
TI  - [Rectorrhage as an unusual extrarenal complication after ESWL].
AB  - We report a case of rectorrhage due to an hematoma of sigmoid colon post ESWL in
      a patient with chronic hepatopathy and right ureteral calculus. We comment the
      clinic and endoscopical study, as well as the review of literature.

PMID- 9658652
TI  - [Inverted papilloma of the ureter. Apropos of a case].
AB  - Presentation of one case of inverted papilloma of the renal pelvis, an uncommon
      entity with very few cases described in the international literature. The
      pathoanatomic presentation is that of a benign tumour, which would provide an
      option for conservative therapy through segmentary resection and termino-terminal
      anastomosis. Due to its low frequency, pre-operative diagnosis of this tumour is
      difficult, although the number of diagnosis could be increased with the use of
      endourologic techniques. In spite of the benign nature, it can be multifocal and
      relapsing. A close follow-up monitoring is recommended.

PMID- 9658654
TI  - [Prostatic abscess caused by anaerobic germs].

PMID- 9658653
TI  - [Bilateral candida bezoar of the upper urinary tract].
AB  - Fungal urinary tract infections are due to candida albicans as first responsible
      germ. This sporulated oval fungus divides itself by gemmation and produces
      pseudohyphas when it is spread in culture mediums, organic tissues or their
      exudates. The most frequent predisposing factor is diabetes mellitus. Others
      predisposing factors are: long antibiotic administration, corticoids,
      immunosuppressors, neoplasias, neurogenic bladder, and catheter or foreign bodies
      into the urinary tract. Bezoar formation is a rare complication that sometimes
      produces obstructive uropathy. Although Candida albicans is the most frequent
      observed germ in bezoars, Candida tropicalis, Penicillium, Aspergillus, Mucor y
      Turolopsis have been found as well. We present the case of a diabetic patient
      with a bilateral bezoar formation into the upper urinary tract due to Candida
      albicans. Clinical features, diagnosis and treatment are described emphasizing in
      the are bilateral onset.

PMID- 9658655
TI  - [Testicular abscess: a manifestation of tuberculosis].
AB  - OBJECTIVE: Presenting 3 cases of tuberculous epididymo-orchitis not very frequent
      presentation without renal or pulmonary involvement. PATIENTS AND RESULTS: 3 old
      males of 65 years went for increase of scrotal volume, pain, fluctuation, and
      pyocele. 2/3 cases had antecedents urologic, any had pulmonary or renal
      antecedents. In the 3 cases there was necessity of practicing trans-scrotal
      orchiectomy, since they went later. The urine cultures, excretory urogram and
      chest films were normals. CONCLUSIONS: In the patients that they got scrotal
      abscess or fistulous tract, should discard tuberculosis.

PMID- 9658656
TI  - Diagnosis and treatment of renal and ureteral calculi.
AB  - Nephrolithiasis affects about 0.2% of the US population annually with about 5% to
      15% of the population suffering at some point in their lives. While 75% of all
      calculi are calcium based, the remainder are composed of uric acid, cystine,
      struvite, or are composed of more than one substance. A 1997 policy update by the
      American Urological Association recommends that stones lodged in the ureter that
      are not causing excruciating pain for the patient are best initially managed by
      observation.

PMID- 9658657
TI  - The use of exhaled carbon monoxide for the diagnosis of carbon monoxide
      poisoning. A case report.
AB  - INTRODUCTION: Carbon monoxide (CO) poisoning is difficult to confirm in small
      rural hospitals that lack easy access to a cooximeter. A small hand held device
      can be used to assess exhaled CO (ECO) in parts per million. This device is often
      used in smoking cessation clinics to confirm that a person has abstained from
      smoking. CASE SUMMARY: A 47-year-old white male became dizzy and had a near
      syncopal episode while working on his boat in the local marina. He was brought to
      the ER and was found to have an exhaled CO level of 180 ppm. The presence
      carboxyhemoglobin (HbCO) was confirmed later by an independent reference
      laboratory and the result was 26% HbCO. DISCUSSION: The patient's exhaled CO
      level dropped slower than expected while breathing oxygen delivered by a non
      rebreather mask. This could be due to inadequate compliance to oxygen therapy and
      a fiO2 somewhat less than 1.0. Another limitation of the technique is the
      calibration gas (50-ppm CO). This concentration may be too low to assess ER
      patients. Therefore a confirmatory ABG with cooximetry should be obtained if
      available. Clinicians are cautioned that there is no safe level of HbCO (6).
      There is a simple formula to convert ECO to HbCO. The use of exhaled CO
      monitoring may be a promising alternative that is relatively less expensive than
      cooximetry in the ER setting, but more research is clearly indicated.

PMID- 9658658
TI  - Medical malpractice tort law--a benighted system.

PMID- 9658659
TI  - [Meningoencephalocele: microsurgical endonasal approach. Report of two cases].
AB  - Neurosurgery is the commonest way of treating meningoencephaloceles, but there
      are cases with certain particularities allowing microsurgical approach through
      the nose, for instance nasoethmoidal sitting, small size,... We report our
      experience of 2 cases of meningoencephalocele removed through this approach, one
      of them reoperated because tumor recurrence.

PMID- 9658660
TI  - [Cavernous hemangioma of the larynx in an adult. Endolaryngeal excision].
AB  - We present a case of cavernous laryngeal hemangioma in an elderly lady. The
      limited surface of the lesion and its location and implantation basis as well
      allowed an endolaryngeal surgery.

PMID- 9658661
TI  - [Craniofacial development in secretory otitis].
AB  - The AA. consider in a population of 76 children, the connexion between bony
      palate, choanae and the M. tensor veli palatini and the occurrence of secretory
      otitis. They measured for this purpose several craniofacial structures "in vivo".
      Children suffering secretory otitis presented, contrary to children without aural
      pathology, a greater incidence of gothic palate (p < 0.001) and a significant
      decrease of both palatine (p < 0.05) and choanae (p < 0.001). All children showed
      going through puberty an palatinal and choanal growth as well a closure of the M.
      tensor veli palatini angle.

PMID- 9658662
TI  - [Influence of the necessity of transfusion in anemia on the prognosis of ENT
      cancer in the protocol with concurrent hyperfractionation of carboplatin and
      irradiation].
AB  - Because of the determinant role of hemoglobin level in blood to the response of
      treatment (viewpoint admitted whether for irradiation or chemotherapic agents)
      the AA. have lead an analysis of a group of 36 patients suffering an advanced
      head and neck cancer (18 months mid-follow up and 30 months maximum) which
      underwent a program of concomitant radio-chemotherapy hyperfraccionated with
      carboplatin (the cytostatic) as part of each therapeutic fraction. The results in
      patients being transfused with an erytrocyte concentrate were compared with those
      from patients not having had any transfusion. The purpose of this study was the
      assessment of which are the influence on the prognostic of ENT-cancer resulting
      of the compulsory necessity of transfunding erytrocyte concentrates aroused by
      serious anemia presenting during the development of the schedule treatment. In
      brief, in that kind of patients needing transfusions of red blood cells
      concentrates because of serious anemia during the treatment (17% of the totality
      treated) were recorded 50% local failures, 33% metastases and only 17% of the
      totality were free of neoplasma at the end of the follow-up fixed. Instead
      between patients not having had transfusions (for treating anemia) the
      differences registered were 20% failures of loco-regional control and 13%
      metastases, whereas 67% were free of tumor at the end of the study. The
      conclusion drawn out is: the important influence on the prognostic of these
      tumors, when in the course of the scheduled treatment, appear severe anemia
      making the transfusions compulsory.

PMID- 9658663
TI  - [Submaxillary sialolithiasis due to Actinomyces israelii. A case report].
AB  - Actynomicosis of the submaxillary gland is a very uncommon infectious disease. In
      this article one case of submaxillary sialolithiasis by actynomices israelii in a
      young girl is presented. We discuss several aspects of its diagnosis and
      therapeutic possibilities and review the literature on the subject. We emphasize
      the interest and value of performing a microbacteriological, mineralogical and
      pathological study of the calculi.

PMID- 9658664
TI  - [Lingual thyroid. A case report].
AB  - Account on a tongue thyroid case and bibliographic review of the subject. It is
      an anomaly due to the thyroid gland not come down. Symptomatic cases are scarce
      (around 400 reported in the literature). Diagnosis is basically scintigraphic.
      When there are symptoms management should begin with thyrotoxine. More severe
      instances require surgical exeresis.

PMID- 9658665
TI  - [Reconstruction of a palatal defect with pedicled myomucosal flap of buccinator
      muscle].
AB  - The myomucosal flap from buccinator muscle is a versatile flap useful on
      reconstruction of defects located in the palatine region. We report the case of a
      vascular tumor located in the left palate which was removed and rebuilt with a
      myomucosal flap taken from buccinator muscle. We proceed previously to the
      embolization of its nutritional artery (a. palatina major).

PMID- 9658667
TI  - [Petrous bone approach for the surgery of petroclival meningiomas].
AB  - Four patients, 3 woman and 1 man, with giant petroclival meningiomata are
      presented. In all cases the tumor size exceed 44 mm in its greater diametre. Main
      clinical symptoms were endocranial hypertension and cranial nerves deficit. A
      modified transcochlear approach in two stages was used. A total petrosectomy was
      performed, using the petrosygmoidal via for opening the dura. Transversus and
      sygmoid sinus were spared. Total removal was achieved in 2 cases, subtotal and
      partly in each of the other 2. No operative mortality occurred (hospital exitus)
      and neurologic morbility related to V-VI-VII and VIII cranial nerves and 1
      hemyparesia was recorded. The AA. explain and comment the fundamentals of the
      followed procedure and compare, as well, the own outcomes with those reported by
      more classic alternatives. Finally, the conclusion is drawn out that retroclival
      meningiomata are conditions treatable, although always are difficulty approached
      and demand meticulous microsurgical techniques.

PMID- 9658666
TI  - [Deep infections of the neck].
AB  - Infections of aponeurotic sheets of the neck are more frequent in men than in
      women. Its etiology although varied is basically related to infectious pharyngo
      tonsillar and dental pathology. In a great deal of cases there are factors which
      predispose clinical manifestations or becoming complications. Early diagnosis and
      precocious specific treatment re-establish the normality in the majority of cases
      but a percentage of them resort to surgery for the condition's control.

PMID- 9658668
TI  - [Efficacy and safety of dotarizine vs. cinnarizine in the symptomatic treatment
      of acute balance disorders (common vertigo)].
AB  - One hundred and ten adult patients suffering from peripheral vertigo were treated
      in a multifactorial double-blind randomized clinical trial with dotarizine (50 mg
      b.i.d.) or cinnarizine (75 mg b.i.d.). There was a 60 days clinical follow-up.
      Results showed that dotarizine was significantly active against the vertigo
      attacks and its associated symptoms (mainly neurovegetative). The global
      superiority of dotarizine was confirmed by statistically significant differences
      between treatments in the improvement of the severity of vertigo, hearing loss in
      audiometries, global relief of symptoms, disability produced by crises and global
      assessment by the investigators themselves. No clinically significant unwanted
      effects were seen in either group on blood pressure, heart rate or analytical
      parameters. No serious adverse effects to dotarizine were reported. This study
      confirms the value of dotarizine in the treatment of peripheral vertigo.

PMID- 9658669
TI  - Comparison of different approaches for a survey of the general population.

PMID- 9658670
TI  - [Microbiological studies of waters of the Alimini Lakes].

PMID- 9658672
TI  - [Dietary exposure to cadmium and mercury].

PMID- 9658671
TI  - [AIDS: knowledge, attitudes and sex behavior of young people attending AIED
      family planning health services].

PMID- 9658673
TI  - [Protection from biological agents in the workplace: considerations on section
      VIII of the Legislative Decree 626/94].

PMID- 9658674
TI  - An early-type hypersensitivity (ETH) to hepatitis B surface antigen as a quick
      and economic screening test for a vaccination program.

PMID- 9658675
TI  - [Monitoring of sterilizer equipment in a large Roman hospital].

PMID- 9658676
TI  - [Fiuggi mineral water: clinical reality and pharmaco-therapeutic attributes].

PMID- 9658677
TI  - [Post-traumatic stress disorder: will the future be different from the past?].

PMID- 9658678
TI  - The epidemiology of chronic fatigue syndrome.

PMID- 9658679
TI  - [Mania: clinical and epidemiological features in different periods of life].

PMID- 9658680
TI  - The epidemiology of eating disorders.

PMID- 9658681
TI  - Can deinstitutionalised care be provided for those at risk of violent offending?
AB  - OBJECTIVE: The aim of this article is to explain the current status of
      deinstitutionalisation and of community care development in the UK. DESIGN:
      Literature review of articles and reports on deinstitutionalisation. SETTING:
      Articles included in the review related either to the whole of the UK, to England
      and Wales, or to a specific area such as London. MAIN OUTCOME MEASURES: The
      review was carried out pertaining to the question of the extent to which
      community care can or should take over the functions of the asylum, with
      particular reference to those at risk of behaving violently. These functions
      include those that are manifest, or explicit, and those that are latent, or
      unintended but implicit (Bachrach, 1976). RESULTS: The example of patients at
      risk of violent behaviour is-one that highlights the continuing relevance of both
      these sets of functions, which are argued to be exerting a powerful influence on
      the processes of asylum closure and community care development. This influence is
      seen in delayed asylum closure, transinstitutionalisation (the shift of some
      patients from asylums to other institutions), and the institutionalisation of
      aspects of community care. CONCLUSIONS: Both the manifest and the latent
      functions of asylums must be acknowledged by those involved in planning community
      care; where it is felt desirable that community care does not take over certain
      functions, the consequences of this must be anticipated so that they can be
      prevented or dealt with in other ways.

PMID- 9658682
TI  - [Physician-patient interactions: a comparison of analysis systems].
AB  - OBJECTIVE: The medical interview has important diagnostic and therapeutic
      functions and requires the integration of doctor-centred and patient-centred
      interviewing techniques to collect accurate and complete biopsychosocial data
      from the patient. Analysis of the interaction between patient and doctors which
      occur during the medical interview allow to evaluate physicians' interview
      techniques and to eventually improve them. OBJECTIVE: 1. To review different
      Interaction Analysis Systems (IAS) used to describe doctor-patient communication
      in terms of clinical relevance, observational strategy, reliability and
      behavioural and verbal contents. 2. To critically evaluate these IASs on the
      basis of their relevant research outcomes. METHOD: Previous reviews on
      interaction and keywords for Medline research (HealthGate) listed above were
      utilised to collect the relevant literature. RESULTS: Seventeen classification
      systems were identified and ten were discussed in a chronological order. Starting
      from a general sociological or psycholinguistic approach, the IASs over the years
      have became more specific and detailed, focusing more on the medical interview
      and on specific topics, such as cancer or hospital medical consultations.
      CONCLUSIONS: When studying interactions in general practice medicine, it is
      important to define the significant units of interaction which allow to identify
      a "patient-centred approach", since this is relevant not only for obtaining
      reliable and complete medical and social data, but also for the recognition of
      patients with emotional disorders and their correct diagnosis. Listening to the
      patient and facilitating the expression of emotions is an important aspect of
      patient education too, as patients learn that talking about psychological
      problems to their physician is appropriate and may be therapeutic.

PMID- 9658683
TI  - [Alcohol Use Disorders Identification Test (AUDIT). Presentation].

PMID- 9658684
TI  - From megakaryocytes to platelets: platelet morphogenesis takes place in the
      bloodstream.
AB  - We studied megakaryocyte processes formed in rat bone marrow and spleen, using
      both the transmission and scanning electron microscopes. Some processes were
      bulky, others slender and beaded. The bulky megakaryocyte processes developed a
      specialized arrangement of organelles at the site at which they entered the
      lumen: filaments present around the outside of the process seemed to support a
      central cylinder in which organelles flowed along microtubules. Megakaryocyte
      processes were present in platelet-rich plasma from both human and rat blood.
      When followed in living preparations, bulky processes developed pointed tips,
      elongated, and became slender and beaded. Fusiform proplatelets also were present
      in the platelet rich plasma, with pointed tips at both ends of what appeared to
      be single "beads"; we assume that the long, beaded megakaryocyte processes would
      have fragmented were we to have had proper culture conditions. The straight,
      shorter fusiform proplatelets in living preparations underwent characteristic
      curving and bending motions, eventually forming disk-shaped cells which sometimes
      had appendages. This behaviour suggests that the entire process of platelet
      morphogenesis takes place in plasma: megakaryocyte processes first elongate, then
      bead and fragment, and then curve and fuse to form disk-shaped platelets. This
      interpretation is strengthened by finding in freshly isolated plasma many of the
      shapes seen in the transformations studied in living cell preparations. The
      megakaryocyte processes and the proplatelets seemed to appear in plasma with a
      periodicity related to light and dark cycles--that is, with a circadian rhythm.
      In particular, megakaryocyte processes appear in human blood within a few hours
      after sunrise; we argue that this might be related to similar peak periods for
      heart attacks.

PMID- 9658685
TI  - A review of the use of teicoplanin in haematological malignancy.
AB  - Factors determining the change in patterns of antibiotic use in patients with
      haematological malignancies include the growing numbers of infections caused by
      Gram-positive pathogens, the increasing reliance on indwelling catheters, and
      strategic movement away from inpatient therapy towards day-case and non-inpatient
      therapy. The suitability of teicoplanin in this context is examined. The
      indications for teicoplanin use are now established as: early use in clinically
      infected patients; as a second-line agent for sensitive pathogens; and in primary
      antibiotic failures. Teicoplanin should not be used as empirical therapy in
      fevers of unknown origin; neither should teicoplanin be used as prophylaxis (the
      situations of infection in chemotherapy patients or for Hickman catheter
      insertion in particular are discussed). Comparative studies versus vancomycin
      have shown teicoplanin to be equally effective and to be well tolerated.
      Teicoplanin's good safety profile and ease of use make it particularly useful for
      non-inpatient therapy. Problems are posed for both glycopeptides by specific
      resistant pathogens, although these pathogens are currently not common.
      Haematologists must be aware of, and guard against, abuse of the glycopeptides in
      their own and other fields, including oral gut decontamination, the treatment of
      Clostridium difficile and veterinary use.

PMID- 9658686
TI  - Non-inpatient parenteral antibiotic therapy in febrile adults.
AB  - Non-inpatient care is becoming an increasingly attractive option in many
      therapeutic areas, including the treatment of infections in patients with
      haematological malignancies. The choice of antibiotics for this care is governed
      by infection patterns and experience within particular institutions. There is an
      increase in infections caused by Gram-positive pathogens due to the long-term use
      of tunnelled catheters and intensive, punishing chemotherapy regimens. Patients
      suitable for non-inpatient care include both long- and short-term patients who
      fulfil specific clinical and social criteria. Haematological malignancy patients
      are often suitable for this type of care. Benefits for patients include improved
      quality of life, while benefits for the clinician include effective, safe care as
      well as reduced costs and greater bed availability. The glycopeptide teicoplanin
      has been assessed for use in non-inpatient care, and is particularly suitable due
      to its long half-life, no need for monitoring and its activity against Gram
      positive pathogens. A comparative study of a teicoplanin-ciprofloxacin
      combination was conducted in inpatients, followed by a cohort study in non
      inpatients. This combination was found to be clinically and microbiologically
      effective, suitable for non-inpatient administration and generated cost savings
      due to early discharge. The organization of a non-inpatient service demands
      dedicated team members, with well-defined roles and a designated treatment area.
      The day ward is the focus of care, which can then take place in the day ward or
      in the patient's home. Good communication between immediate and wider team
      members, and patient education are cornerstones of a successful service.

PMID- 9658687
TI  - Experience with teicoplanin in non-inpatient therapy in children with central
      line infections.
AB  - Indwelling intravenous catheters are an invaluable part of the curative therapy
      or terminal care of children with haematological malignancies. The increase in
      their use has been paralleled by an increase in Gram-positive infections,
      however. This article provides an overview of non-inpatient treatment of central
      line infections using teicoplanin. The main drivers for considering non-inpatient
      therapy were to increase the quality of the patient's life by reducing the amount
      of time spent in hospital, and to prolong the life of the catheter. A large
      proportion (95%) of the children in the unit described have indwelling catheters
      in situ, including Port-a-caths, Hickman catheters and Vascaths. The indications
      suitable for non-inpatient antibiotic therapy of line infections were those
      patients near the end of their chemotherapy courses, during terminal care, in non
      neutropenic patients to complete an antibiotic course, and in patients with
      chronically neutropenic aplastic anaemia. Persistent line infections are not
      always eradicated but usually controlled. Care can take place in the home, in the
      general practitioner (GP) surgery or in the outpatient clinic. Care can be
      undertaken by nurses, older patients and parents. Follow-up procedures are in
      place to ensure safe, effective therapy.

PMID- 9658688
TI  - Central venous catheter infections treated with teicoplanin.
AB  - A novel way of using teicoplanin in situ to treat central venous catheters is
      described. Profound immunosuppression and the fact that the lines remain
      indwelling for long periods are two of the main reasons for these infections. In
      children it is also difficult to prevent these lines being played with, which
      increases the likelihood of infection. The different types of infection that can
      occur in a central venous catheter are described and the clinical definition of a
      catheter infection is provided. In an initial study, infective episodes in a
      small group of 11 children were treated successfully with in situ amikacin. Most
      pathogens were Gram-negative cocci. None of the catheters had to be removed, and
      catheter life was prolonged by a mean of 118 d. Due to the high incidence of
      Staphylococcus epidermidis in the initial study, in situ teicoplanin was assessed
      in a subsequent study. Over the course of 1 yr, 20 line infections occurred in 12
      children. Empirical amikacin therapy was instituted and switched to teicoplanin
      once the pathogen was confirmed as Gram-positive. An antibiotic-heparin mixture
      was introduced into the line and left in place for 24 h, after which time it was
      replaced with fresh mixture until cultures were sterile. All pathogens were
      sensitive to teicoplanin, all infections were treated successfully and no
      catheters had to be removed. Overall, catheter life was prolonged by a mean of
      136 d. It was concluded that in situ teicoplanin was effective and well tolerated
      for line infections (no side-effects were reported during the study). A minimum
      of 6 d therapy was recommended. The patients with less severe infections would
      have been suitable for treatment at home by their parents, district nurse or
      general practitioner (GP).

PMID- 9658689
TI  - Patient education and communication in non-inpatient intravenous therapy--a
      review.
AB  - This paper reviews patient education and communication elements of non-inpatient
      intravenous therapy schemes in the United States and the United Kingdom. Common
      characteristics of these services include: definition of the components of the
      scheme at all levels; patient selection; patient education; and good
      communications. A metaplan carried out among UK healthcare professionals
      highlighted education and communication issues as important factors for ensuring
      successful therapy. Communication issues are difficult to define or modify.
      Specific experience from the United States and the United Kingdom is presented
      and the common elements in these programmes are emphasized. Results of the
      assessment of patient education are presented. This collective experience may
      prove useful for other centres setting up similar therapy schemes.

PMID- 9658690
TI  - [Restoration of root canal treated teeth using carbon fiber posts].
AB  - The restoration of root canal treated teeth--because of the significant loss of
      tooth structure--is often achieved with post and core. However, post may generate
      stresses which lead to vertical root fracture and loss of the tooth. Since post
      design, material used and the post space preparation has significant influence on
      vertical fracture prevalence, broad investigation is in progress to find out the
      optimum procedure. During the last decade new prefabricated passive posts were
      introduced for postendodontic restorations. In order to collect information
      clinical trials have been performed on the reconstruction of root canal treated
      teeth using carbon fibe posts (COMPOSIPOST, RTD, France; C-POST, Bisco, USA).
      Adhesive technique was applied to cement posts in the root canal and for
      composite core reconstruction. The physical properties of carbon fiber posts and
      the composite core are very close to those of dentin. Post application is simple,
      does not require special skill and for the patients means minimum hazard. The
      position of the posts was controlled by radiography. During the 24 months
      observation period no failure was registered in patients treated (n = 55). Hence,
      we attribute our good results to the homogeneous reconstruction of the teeth.
      This procedure seems to be a good alternative to traditional cast metal
      dowel/cores or metal prefabricated posts.

PMID- 9658692
TI  - [The development of the Simon system and its use in combination with multi-band
      technic].

PMID- 9658691
TI  - [Efficacy of short-term danazol treatment in hereditary angioneurotic edema
      patients undergoing maxillofacial and dental surgical procedures].
AB  - The authors evaluated the efficacy of short-term danazol prophylaxis in 12
      hereditary angioedema patients undergoing maxillofacial or dental procedures.
      Hereditary angioedema is an autosomal dominant disorder resulting from the
      deficiency of the C1 esterase inhibitor. Characteristic clinical manifestations
      include the formation of subcutaneous and submucosal edema. The latter can lead
      to fatal upper airway obstruction. Edematous attacks can be precipitated by
      tissue injury from operative procedures, dental surgery in particular. In
      patients undergoing surgical and diagnostic procedures performed in the cephalic
      and cervical regions, such attacks can be prevented by appropriate drug therapy.
      Short-term danazol prophylaxis was effective in all 12 patients with a history of
      edematous complications that had occurred after dental procedures; none of them
      developed postoperative edema. The serum levels of complement components
      determined pre- and postoperatively as well as at 6- and 12-hour intervals also
      demonstrated the efficacy of prophylactic therapy.

PMID- 9658693
TI  - [Final results of the administration of biosynthetic growth hormone. Preliminary
      report].
AB  - From March, 1987 to November, 1995, we have included 89 growth hormone-deficient
      children for treatment for their low height with the biosynthetic growth hormone;
      23 of them have concluded treatment. Without taking into account the etiological
      factor of their deficiency, 6 girls and 17 boys during different lapses had
      modified their initial height and the scores of the standard deviation as groups,
      range from 113.11 +/- 14.83 cm and -5.12 +/- 1.21 to 139.11 +/- 8.96 cm. and 
      2.68 +/- 1.17 in the girls, and from 128.46 +/- 12.49 cm and -4.13 +/- 1.35 to
      158.61 +/- 6.47 cm and -1.76 +/- 0.9 in the boys, respectively. These results
      between the initial height and the score of the standard deviation compared with
      the final height and the standard deviation score, showed a statistically
      significant difference of p < 0.001 both in girls and boys. Two girls and 3 boys
      developed hypothyroidism during the treatment, without any other side effect. We
      concluded that early and prolonged biosynthetic growth hormone administration in
      growth hormone-deficient children might produce a final adult height similar to
      the normal population standards.

PMID- 9658694
TI  - [Comparative study of tympanic and mercury thermometry in children].
AB  - The aim of the study was to evaluate tympanic thermometry when compared with
      conventional glass-mercury thermometry, in 186 consecutive pediatric patients. In
      patients of less than 6 years of age (n = 120), there were no differences between
      tympanic and rectal measurements, in febrile and afebrile ranges, and
      significantly different when compared with axillary range. Similar data were
      reported in children of more than than 6 years of age (n = 65), in whom oral
      temperatures replace the rectal one. Using the tympanic thermometer as the
      standard measurement device, the accuracy of rectal, oral and axillary
      thermometers in determining a febrile state was examined. When tympanic
      temperature was 38 degrees C, a febrile state was considered, in this condition
      sensitivity for rectal measurement was of 73%, for oral 64%, and 23 and 29% for
      the axillary, according to the age group: specificity was of 100% in all the
      them. According to our data, tympanic measurement was consistent with glass
      mercurial, rectal and oral, temperature in a pediatric population. Advantages of
      tympanic thermometry are its good correlation with central temperature,
      substantial time reduction of measurement (1 second), easy and non-invasive
      procedure, improved patient comfort, and lack of mercurial thermometry
      disadvantages. The conclusion is that tympanic thermometry becomes an acceptable
      option for pediatric temperature measurement.

PMID- 9658695
TI  - [Chronobiological profile of arterial blood pressure and heart rate in a family
      group determined by automatic monitoring].
AB  - Over a week, blood pressure (systolic, mean and diastolic) and heart rate were
      determined in a family, by means of automatic, uninterrupted monitoring. The
      chronobiological profile for each family member was prepared in time series of
      various periodicities. An ample circadian component and a lesser circaseptan
      component were apparent. Clear phase differences were identified among the four
      cardiovascular variables studied. The chronobiological profile of the children
      was closer to that of the father than to that of the mother.

PMID- 9658696
TI  - [Usefulness of the ASA scale and thoracic radiography as indicators of
      perioperative cardiovascular risk].
AB  - This paper evaluates the usefulness of ASA physical status classification and the
      multifactorial index of cardiac risk in the preoperative assessment, without
      considering arterial blood gases. With the results of this study we propose to
      add the ASA physical status classification, the radiologic diagnosis of chronic
      obstructive pulmonary disease and the multifactorial index of cardiac risk. This
      strategy increases the diagnostic certainty of Goldman's index of cardiac risk,
      is practical, not expensive and favors a better establishment of the risk of
      perioperative cardiovascular morbidity.

PMID- 9658697
TI  - [Presidents of the Academy in the 20th century. Their thought].

PMID- 9658698
TI  - [The general practitioner in Mexico: present and future].

PMID- 9658699
TI  - [Neurosteroids. Neuromodulators of cerebral excitability].
AB  - Steroids which are produced by the brain are called neurosteroids, and they are
      able to modulate neurotransmissions: GABAergic; glutamatergic; glycinergic, and
      cholinergic (nicotine receptor). These effects are of short latency and duration,
      and do not implicate the cellular genome. The interaction of these neurosteroids
      with membrane receptors contribute to the regulation of neuronal excitability,
      and their study has allowed a better understanding of cognitive, hormonal, and
      epileptic phenomena as well as the development of new drugs with anxiolytic,
      antidepressive, anesthetic and anti-epileptic effects.

PMID- 9658700
TI  - [Treatment of diabetic neuropathy].
AB  - Diabetic polyneuropathy is a complication, that affects most patients with
      longstanding diabetes mellitus, deteriorating their quality of life. In the last
      few years, new therapeutic approaches have been developed that can improve
      symptoms and neurologic function, and which may prevent and in some cases stop
      nerve damage, and even, promote nerve fiber regeneration. These treatments are
      supported by several investigations in animals and humans: a) thigh glycemic
      control (insulin), b) aldose reductase inhibition (tolrestat), c) prevention of
      protein glycation (amino-guanidine), d) improvement of nerve ischemia (vaso
      dilators, gamma-linolenic acid), and e) administration of neurotrophic factors
      (gangliosides). Most evidence support the usefulness for glycemic control. Early
      treatment is suggested, because marked nerve fiber loss is present in advanced
      neuropathy.

PMID- 9658701
TI  - [Dr. Carlos Adalid and heart catheterization].

PMID- 9658702
TI  - [Surgical treatment of invasive thymoma with superior vena cava syndrome. 3 case
      reports].
AB  - Three patients with invasive thymoma and superior vena cava syndrome with severe
      symptoms of cerebral venous hypertension and respiratory obstruction are
      presented. Two patients showed a type I obstruction and the other had a type II
      obstruction as defined by Stanford and Doty. In all of them, the tumor was
      resected and a graft bypass was placed between the left innominate vein and the
      right appendage. In two patients the grafts were venous and in the other it was a
      PTFE. All grafts were reinforced with wire rings. The patients improved and the
      symptoms of the SVCS disappeared, the average time of permeability was 10 months.

PMID- 9658703
TI  - [Tridimensional representation of left ventricular perfusion during
      pharmacological stress and rest in patients with myocardial ischemia].

PMID- 9658704
TI  - [Infectious proteins or prions. A new mechanism of disease].

PMID- 9658705
TI  - [Obesity has gone from being a cosmetic problem to being a health problem].

PMID- 9658706
TI  - [Gastric cancer and its relations with life style].

PMID- 9658707
TI  - [The physician, ethics and the law].

PMID- 9658708
TI  - ["Evidence-based medicine"--guidelines as a threat or necessity for physician and
      patient?].
AB  - Guidelines derived from 'evidence-based medicine' are supposed to provide
      assistance and information in order to improve diagnosis and therapy of
      individual patients and build up confidence in medical decisions. Guidelines
      possess no direct legal power. The doctor's freedom of decision must be
      warranted. Inadequate guidelines may have serious consequences: curtailment of
      therapeutic freedom, hampering of medical progress, deterioration of the
      relationship between doctors and their patients, risk of legal implementation and
      emergence of a defensive medicine.

PMID- 9658709
TI  - [Operation or irradiation of cervix carcinoma?].
AB  - Treatment of early invasive carcinoma of the uterine cervix by radical surgery or
      radiation continues to engender controversy after many decades of effective
      therapy. A recently published first prospective randomised trial revealed that
      stage I and IIa cervical carcinoma can be cured by radical surgery or
      radiotherapy with an identical 5-year survival (83% in both groups) and a similar
      recurrence rate (25 vs. 26%). In many points, a prospective Italian study
      confirms the retrospective results of our previous published studies. Surgery and
      radiotherapy alone are equally effective but differ in associated complications.
      Severe morbidity occurred in the Italian study after surgery and radiotherapy
      alone in 28 and 12%, respectively (p < 0.0004). In our retrospective study,
      severe complications were found with surgery and adjuvant radiation in 36.4%,
      with radiotherapy alone in 13.7% (p < 0.001). The usefulness of postoperative
      radiation is not clear, and patients should not be subjected to both therapies.
      Optimum candidates for primary radical surgery are women with normal ovarian
      function and cervical diameters of 4 cm or smaller. Adenocarcinomas of the
      uterine cervix are better treated with surgery (5-year survival 66 vs. 47%, p <
      0.02).

PMID- 9658710
TI  - [Intracytoplasmic injection of epididymal and testicular sperm after failed
      heterologous insemination].
AB  - We report on our experiences with intracytoplasmic injection (ICSI) of epididymal
      and testicular spermatozoa (MESA, TESE) from azoospermic men whose wives had
      previously failed to become pregnant after several cycles of artificial
      insemination by donor (AID); because we do not perform AID treatment in our
      clinic, all these treatments were carried out in other fertility centers as well
      as the female diagnostic of sterility. In 3 husbands we could not find any
      testicular spermatozoa or spermatids, leaving 15 women under treatment. Of these
      15 women, 9 became pregnant. This accounts for a pregnancy rate per patient of
      60%. We believe that functional defects of the oocytes and somatizing
      psychological problems concerning AID are predominantly responsible for these
      results and that both problems can be overcome by ICSI. Besides, these results
      demonstrate that ICSI/MESA and ICSI/TESE are effective approaches in the
      treatment of azoospermic men and that using cryopreserved spermatozoa is not
      disadvantageous in the outcome of ICSI.

PMID- 9658711
TI  - [Role of gravidin, a phospholipase A2 inhibitor, in uterine contraction].
AB  - OBJECTIVE: What is the significance of gravidine, a phospholipase A2 inhibitor,
      in parturition? METHODS: Gravidine concentrations were measured in amniotic fluid
      obtained by transabdominal amniocentesis from women in labor at term and not in
      labor using a sensitive and specific ELISA. RESULTS: (1) Amniotic fluid gravidine
      concentrations were lower in the presence than in the absence of labor. (2)
      Gravidine concentrations in the amniotic fluid of the forebag were higher than in
      the amniotic fluid of the upper compartment. (3) There was a positive correlation
      between gestational age and amniotic fluid gravidine concentrations. (4) No such
      correlation could be demonstrated between cervical dilatation and amniotic fluid
      gravidine concentrations. CONCLUSION: These results suggest that gravidine may
      play a permissive role in the interplay with prostanoids in the mechanism of
      parturition.

PMID- 9658712
TI  - [Detection of endometriosis during cesarean section for HELLP syndrome in the
      32nd week of pregnancy].
AB  - The rare case of a decidualized endometriosis of the appendix vermiformis is
      reported in a woman who developed HELLP syndrome during the 32nd week of a twin
      pregnancy. Cesarean section and simultaneous appendectomy were performed. An
      inspection of the appendix should always be carried out if an endometriosis
      associated anamnesis is known. No pathophysiological correlations between the
      HELLP syndrome and the endometriosis of the appendix vermiformis could be found.

PMID- 9658713
TI  - [Obstetrics--a gear in the machinery of history].
AB  - It was not Julius Caesar who was born by Caesarean section, as generally assumed,
      but Scipio Cornelius Africanus, who subdued Spain 100 years before Caesar's time.
      In chambers with walls of porphyrite, the Byzantine empresses used to give birth
      to the heirs to the throne. In England, the infertility of Queen Anne, who
      suffered from porphyria, led to the succession of the Protestant House of
      Hannover following the Catholic Stuarts. Christina of Sweden, called 'queen of
      baroque, rebel and scholar', was born in the 'caul'. At the age of 39 years,
      Johanna of Pfirt, married to Albrecht the Lame, secured the continuation of the
      Habsburg dynasty by giving birth to Rudolf the Founder. Maria Theresia, who had
      16 children, was called 'mother-in-law of Europe'. She was delivered of her first
      child at the age of 19. The death of her sister Maria-Anna in childbed was one of
      the reasons why Gerard van Swieten was called to Vienna. Elisabeth of
      Wurttemberg, first wife of Franz I of Austria, died, not as a consequence of. but
      after a forceps operation carried out by Johann Lukas Boer. In England, Princess
      Charlotte, daughter of George IV, and her baby son died at the delivery; Sir
      Richard Croft, who had not used the forceps, committed suicide after this tragic
      incident. Being the next in succession, Victoria ascended the throne. The term
      'narcose au chloroforme' (first used by James Young Simpson) was changed to
      'narcose a la reine' after this method had been used at the birth of Victoria's
      eighth child by John Snow. It was Queen Victoria, who passed on haemophilia in
      European dynasties. When Marie Louise of Habsburg had her first child, Napoleon's
      son, the later Duke of Reichstadt, Antoine Dubois had to perform a turning of the
      transverse presentation and use the forceps on the head following after. The
      birth of Napoleon himself was a case of precipitate labour. Johann Klein, the
      successor of Boer, applied the forceps when Archduchess Sophie was delivered of
      her first child, the later Emperor Franz Joseph I of Austria, the first of the
      four 'salt princes'. The later Emperor Wilhelm II of Prussia was delivered by
      Eduard Arnold Martin the Elder, the obstetrician of Princess Victoria, the eldest
      daughter of Queen Victoria; the breech presentation became even more complicated
      by the raised arms of the child. Both latter monarchs had been 'asphyctic' after
      their birth. Johann Wolfgang von Goethe was also among those who were apparently
      dead after their birth.

PMID- 9658714
TI  - [Guidelines for the management of simple ovarian cysts. A consensus report by AGO
      and AGE by request of OGGG. Austrian Society of Gynecology and Obstetrics].

PMID- 9658715
TI  - [40 years Austrian Society for the Study of Sterility and Fertility].
AB  - The Second World Congress of the International Fertility Association (IFA) in
      Naples in 1956 permitted only the participation of national fertility societies
      with interdisciplinary structures: gynecology, andrology and veterinary medicine.
      This short historical review shows the situation at the time of the foundation of
      the Austrian Society for the Study of Sterility and Fertility regarding the
      preparations as well as the members of the founding committee.

PMID- 9658716
TI  - [The role of nitric oxide in reproduction].
AB  - Nitrix oxide (NO) is a highly reactive and short-lived radical (half-life time:
      10-12 s), which is derived from L-arginine by the NO synthases (NOS) in several
      organ systems. The release of NO by endothelial cells leads to rapid relaxation
      of vascular smooth muscle cells, whereas release by several neuronal cells causes
      neurotransmission. When NOS is actively induced in immune cells or certain
      epithelia it causes cytotoxicity and/or apoptosis of these cells. In the
      reproductive organs NO is now considered to be an important trigger molecule for
      several physiological mechanisms. Follicular synthesized NO is involved in
      rupture of the follicle during ovulation. Moreover, NO participates in the
      acrosome reaction of spermatozoa during capacitation. Apoptosis and
      collagenolysis of the functional endometrium may be involved in endometrial
      shedding during menstruation. Since NO induces both apoptosis and collagenolysis,
      the newly discovered production of NO in late secretory endometrium could act as
      a key mechanism in the process of menstrual disintegration of the endometrium.
      Additionally, NO is necessary to support and maintain the decidualization process
      and plays a pivotal role in implantation.

PMID- 9658717
TI  - [Menstrual cycle anomalies in young girls--prognosis concerning later fertility].
AB  - Menstrual disorders in adolescents should be investigated promptly to avoid or
      alleviate possible long-term sequelae, including impaired fertility. Patients
      with uterine amenorrhea cannot become pregnant. The prognosis for later fertility
      in patients with oligoamenorrheas depends on the pathogenesis and degree of the
      condition. Hypothalamic oligoamenorrheas generally resolve when the offending
      stimuli are removed, and the prognosis for future fertility is good. In patients
      with pituitary lesions, even those with complete loss of pituitary function,
      pregnancies can be achieved and maintained with exogenous gonadotropins.
      Menstrual disorders due to hyperprolactinemia can be treated effectively.
      Hyperandrogenemic oligoamenorrheas, especially the polycystic ovary syndrome, are
      common. Future fertility has been improved with preventive measures in
      adolescence and later interventions. Patients with primary ovarian insufficiency
      and persisting hypergonadotropic amenorrhea have a poor prognosis. A new aspect
      is the restitution of ovarian function after treatments for malignant diseases.

PMID- 9658718
TI  - [A pill for the man? Current status of fertility control in the man].
AB  - Taking all facts into consideration from animal experiments and clinical studies
      with regard to the development of a male contraceptive you must be aware that the
      'pill for men' will hardly be available in this century. Because of the
      increasing interest of the industry and the effort of the WHO and other similar
      institutions, like the Population Council of New York, to develop a male pill the
      stagnation of the past 20 years could be overcome, and it may be possible to have
      an adequate method in 2005. In all probability this will be a combination of
      hormones either from a gestagen plus testosterone preparation or a potent LHRH
      agonist and/or antagonist, also in combination with a long-acting testosterone
      preparation, with testosterone levels within the normal range. Nowadays it cannot
      be said which role gossypol will finally play. There are studies going on with
      gossypol with some promising results.

PMID- 9658719
TI  - [Does the "impact factor" kill the German language?].

PMID- 9658720
TI  - Effect of PEG-recombinant human megakaryocyte growth and development factor (PEG
      rHuMGDF) on growth and differentiation of the HEL cell line.
AB  - BACKGROUND AND OBJECTIVE: Thrombopoietin has been established as the major
      regulator of megakaryocyte and platelet production. In this study we evaluated
      the effects of PEG-recombinant human megakaryocyte growth and development factor
      (PEG-rHuMGDF), a pegylated and truncated form of thrombopoietin, on the growth
      and differentiation of the HEL cell line. As a model system we chose the
      pluripotent HEL line that acquires multiple markers of the megakaryocyte/platelet
      phenotype following treatment with phorbol esters, and, more importantly,
      expresses the receptor for thrombopoietin (Mpl receptor) at its cellular surface.
      DESIGN AND METHODS: The effect of PEG-rHuMGDF on HEL
      proliferation/differentiation was evaluated in a liquid culture assay. RESULTS:
      Peg-rHuMGDF do not increase the proliferative capacity of HEL cell but, in
      parallel experiments, HEL cells showed a more mature and differentiated pattern
      after exposure to the cytokine. Our results show that PEG-rHuMGDF, at the optimal
      doses of 100-150 ng/mL, is able to induce: 1) morphological changes with the
      formation of cytoplasmic protrusions; 2) increased ploidy as demonstrated by
      cytofluorimetric analysis; 3) increased expression of megakaryocyte markers,
      including glycoprotein IIb-IIIa and the platelet-specific alloantigen (PIA1).
      INTERPRETATION AND CONCLUSIONS: These findings show that HEL cells represent a
      useful model to investigate the differentiative properties of thrombopoietin in
      the megakaryocyte compartment.

PMID- 9658721
TI  - CD117 (c-kit) is a restricted antigen of acute myeloid leukemia and characterizes
      early differentiative levels of M5 FAB subtype.
AB  - BACKGROUND AND OBJECTIVE: The CD117 molecule is an antigen more frequently found
      on early normal and leukemic hematopoietic cells, but its correlation with the
      FAB subtypes and with other lineage and stage associated antigens is still not
      well established. In this study we investigated the surface expression of CD117
      antigen in 135 patients with acute leukemia in relationship to de novo or
      secondary origin of AML, subtypes of FAB classification, expression of other
      antigens such as CD34, HLA-DR, CD15, CD14, CD45RA, CD45RO, CD11b, CD11c, CD4,
      CD7, mixed antigen co-expression (LyAg + AML and MyAg + ALL) and features of
      leukemic mass. DESIGN AND METHODS: The CD117 antigen expression (clone 95C3) was
      determined by flow cytometry in a series of 135 patients with acute leukemia at
      diagnosis consecutively observed during the years 1995-1997: 82 AML (including 51
      cases of de novo AML, 22 cases of AML following myelodysplastic syndromes (MDS),
      9 cases of myeloid blastic crisis of chronic myeloid leukemia (BC-CML) and 53
      ALL. All cases were stratified in CD117+ and CD117- groups and the differences
      were analyzed by using appropriate statistical analyses. RESULTS: CD117 antigen
      was found over 10% in 74% of AML without significant differences of positivity
      between AML after MDS or BC-CML and de novo AML. We did not note a significant
      correlation between FAB classification and CD117 which was expressed in 100% of
      M1 and M7 cases, in 80% of M0 cases, in 75% of M2 cases, in 70% of M3 cases and
      in 82% of M4 cases. Instead, in M5 subtype CD117 was strictly restricted to
      earlier stages: ten of the eleven M5b (91%) cases completely lacked CD117 antigen
      expression, whereas 100% of M5a cases were positive. The results of Pearson's
      coefficient showed: 1) a significant inverse relationship between CD117 and CD15,
      CD4 and CD14 (only in M5 subtypes) and CD11b, CD11c and CD45RO (in all cases); 2)
      a significant direct correlation between CD117 and CD34 and CD45RA (in all
      cases); and 3) an independent expression between CD117 and CD15 associated with a
      low correlation between CD117 and HLA-DR antigen (only in non-monocytic cases).
      In ALL, whether of B or T lineages, surface expression of CD117 was never
      observed. INTERPRETATION AND CONCLUSIONS: We conclude that the CD117 antigen
      shows a high specificity for AML, independently upon FAB classification, and
      represents a reliable marker in characterizing the differentiative degree of the
      monocytic blasts.

PMID- 9658722
TI  - CD27 in B-cell chronic lymphocytic leukemia. Cellular expression, serum release
      and correlation with other soluble molecules belonging to nerve growth factor
      receptors (NGFr) superfamily.
AB  - BACKGROUND AND OBJECTIVE: CD27, a transmembrane homodimer belonging to the nerve
      growth factor (NGF) receptor superfamily, is typically expressed on leukemic CD5+
      cells in B-cell chronic lymphocytic leukemia (CLL) and found in soluble form in
      the serum of CLL patients. Therefore, we investigated clinico-biological
      implications of increased serum levels of sCD27 in an unselected series of B-CLL
      patients. DESIGN AND METHODS: Serum CD27 (sCD27) levels were determined at the
      time of diagnosis in 82 previously untreated B-CLL patients using a sandwich
      enzyme-linked immunoassay (ELISA). Results were correlated with either clinico
      hematological or biological features. Finally, quantitative flow cytometric
      analyses of membrane CD27 (mCD27) expression were carried out on peripheral blood
      (PB) cells of 22 B-CLL patients and 5 healthy controls, respectively. RESULTS:
      CD27 was found to be expressed on the surface of both resting normal and leukemic
      B cells. sCD27 levels were significantly higher in B-CLL patients (median value
      2150 U/mL) than in healthy controls (median value 220 U/mL) (p < 0.0001). There
      was a close relationship between sCD27 and soluble TNF-alpha, another molecule
      belonging to the NGF receptor superfamily. Changes in sCD27 level correlated with
      clinical stage, beta 2 microglobulin and LDH. INTERPRETATION AND CONCLUSIONS:
      These findings indicate that sCD27 is a reliable marker of tumor mass in B-CLL.
      Its potential prognostic value should be tested in prospective studies.

PMID- 9658723
TI  - Microsatellite analysis in childhood acute lymphoblastic leukemia.
AB  - BACKGROUND AND OBJECTIVE: Genetic alterations, including genomic instability,
      represent possible steps towards a malignant transformation. One approach to
      delineate replication errors in cancer cells is to determine alterations of
      microsatellites that are short tandem repeat sequences dispersed throughout the
      human genome. We have investigated whether genomic instability may be a possible
      event in the leukemogenic process by evaluating the pattern of instability in 41
      cases of childhood acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS:
      Eighty-two samples of genomic DNA (41 at diagnosis and 41 at remission) were
      analyzed by PCR with microsatellite markers chosen on five different chromosomes
      (2, 10, 11, 13, 18) known to be frequently involved in tumors of various origins.
      Since deletions of the short arm of chromosome 12 are relatively common in
      children with ALL, we also analyzed one region flanked by the microsatellite
      marker D12S308 on 12p. This area encompasses a genetic locus which contains the
      putative suppressor gene KIP1. RESULTS: A pattern of MI at one or two loci on
      different chromosomes could be documented in 4 of the 41 cases analyzed (9.7%).
      Three were common ALL and 1 was a T-ALL. One case showed two concomitant sites of
      instability, while 1 revealed two additional bands by using simultaneously
      microsatellite markers D2S123 and D18S58. INTERPRETATION AND CONCLUSIONS: These
      results indicate that genetic instability of microsatellite repeat sequences
      occurs in a proportion of childhood ALL. Mismatched repair errors documented in
      hereditary and sporadic solid tumors may thus be involved in hematological
      malignancies. While in such cases the pattern of genomic instability appears
      indicative of a mutator phenotype and of a potential predisposition towards a
      leukemic transformation, other genomic loci close to cytogenetic and molecular
      alterations known to occur in ALL need to be investigated in depth in cases with
      an apparently non mutated phenotype.

PMID- 9658724
TI  - Conventional cytogenetics and FISH evaluation of chimerism after sex-mismatched
      bone marrow transplantation (BMT) and donor leukocyte infusion (DLI).
AB  - BACKGROUND AND OBJECTIVES: Sensitive and quantitative cytogenetic methods to
      better assess the biological significance of post-BMT chimerism have been
      recently developed. In this study, we compared the results of chimerism analysis
      and evolution employing conventional cytogenetics and fluorescence in situ
      hybridization (FISH) in 16 patients after sex-mismatched BMT, and in 5 patients
      after donor lymphocyte infusion (DLI) to treat post-BMT relapse. DESIGN AND
      METHODS: FISH studies were performed using separate digoxigenin labeled
      centromeric DNA probes for the X (pDMX1) and Y (DYZ1/DYZ3) chromosomes. To this
      purpose, different types of samples were used: bone marrow (BM) and peripheral
      blood (PB) slides processed for conventional cytogenetics, and routine BM and PB
      smears. RESULTS: Results of chimerism studies performed on different types of
      samples showed no significant differences. No significant differences in the
      ability to identify the sex of each cell with both pDMX1 and DYZ1/DYZ3 probes
      were found and the results obtained from independent experiments showed a high
      linear correlation. Chimerism analysis by FISH showed initial mixed chimerism
      after BMT in 10 patients. Seven of these patients were also studied by
      conventional cytogenetics and 2 of these showed mixed chimerism. Seven of the
      former 10 patients evolved to complete donor chimera. 6 patients showed
      cytogenetic or hematologic bone marrow relapse, 3 of which were preceded by mixed
      chimaerism as revealed by FISH studies. FISH studies permitted an easy and
      accurate monitorization of the response to DLI in 5 relapsed patients, showing an
      increase in the proportion of donor cells in 4 patients as they reached a new
      complete remission. INTERPRETATION AND CONCLUSIONS: Both FISH and conventional
      cytogenetics are quantitative methods to assess chimerism. However, FISH is more
      sensitive, accurate and can even be applied on routine BM and PB smears.
      Furthermore, its combination with immunophenotyping approaches to quantify
      chimerism on cell subpopulations, will help to clarify post-BMT chimerism
      significance.

PMID- 9658725
TI  - Renal complications in acute leukemias.
AB  - BACKGROUND AND OBJECTIVE: Renal failure is a known complication of acute
      leukemias both at diagnosis and following cytostatic treatment. No recent studies
      give data on the incidence and risk factors of renal complications and their
      prognostic impact. DESIGN AND METHODS: Two hundred and twenty consecutive adult
      patients with newly diagnosed acute leukemia treated at a major university
      medical center were evaluated for renal complications before, during, and after
      treatment; 166 patients were treated by chemotherapy only and 54 patients were
      treated with chemotherapy and later transplanted with allogeneic or autologous
      bone marrow. Renal complications were subdivided into 3 entities: acute renal
      failure, major and minor complications, based on clinical and laboratory
      parameters. Renal failure occurring as a consequence of terminal multi-organ
      failure was excluded from the present study. RESULTS: Approximately 30% of
      patients in the chemotherapy group had a renal complication either before or
      after chemotherapy. Patients undergoing transplantation had a 50% risk of renal
      complications. Risk factors for complications were male sex, age, previous kidney
      disease, white cell count, and refractory leukemia (chemotherapy group) and
      allogeneic versus autologous transplant (transplant group). In the chemotherapy
      group, early but not delayed renal complications had a poor prognostic impact. In
      the transplant group renal complications had no impact on prognosis. In all
      patient groups, acute renal failure was prognostically unfavorable.
      INTERPRETATION AND CONCLUSIONS: We conclude from our study that renal
      complications are frequent in acute leukemias and that the treatment and
      prevention of renal complications is important for the management of acute
      leukemias.

PMID- 9658726
TI  - A new combination of carboplatin, high-dose cytarabine and cross-over
      mitoxantrone or idarubicin for refractory and relapsed acute myeloid leukemia.
AB  - BACKGROUND AND OBJECTIVE: High-dose cytarabine (HIDAC) and new anthracycline-type
      drugs (mitoxantrone, idarubicin) are the mainstay of several active regimens
      against relapsed and refractory acute myeloid leukemia (AML). The present study
      was undertaken to assess the feasibility, toxicity, and antileukemic activity of
      carboplatin (CBDCA) added to a combination of the two former agents. DESIGN AND
      METHODS: Two regimens (R) of CBDCA plus HIDAC and either mitoxantrone or
      idarubicin (crossover) were sequentially evaluated. R-1 consisted of CBDCA 300
      mg/m2/d (24-hour infusion) on days 1-4, HIDAC 1 g/m2/bd on days 1-5, and
      mitoxantrone/idarubicin 12/6 mg/m2/d on days 1-3, followed by granulocyte colony
      stimulating factor (G-CSF). R-2, an attenuated-toxicity regimen, consisted of
      CBDCA and G-CSF as above, HIDAC on alternate days (1, 3, 5), and
      mitoxantrone/idarubicin 8/5 mg/m2/dose. Intended post-remission therapy included
      a similar, lower intensity course and a myeloablative phase supported by an
      allogeneic or autologous blood cell transplant. RESULTS: Twenty-nine patients
      (median age 53 years, one child) formed the study group: 10 (34%) had a primary
      refractory disease (8 to idarubicin-cytarabine-etoposide, ICE), 6 (21%) were at
      second or subsequent relapse, and 5 (17%) had a first remission lasting < 12
      months. In addition, 4 patients (14%) had received prior HIDAC and 10 (34%) were
      relapsing after a bone marrow/blood cell transplant. Twelve patients were treated
      with R-1 and 17 with R-2. The complete response rate was 25% with R-1 and 53%
      with R-2, due to a significantly lower death rate by pancytopenic complications
      (p = 0.023). The probability of response by risk class was: primary refractory
      30% (43% with R-2), > 2nd relapse 33% (50% with R-2), 1st relapse < 12 months 40%
      (50% with R-2), 1st relapse > 12 months 50% (75% with R-2), prior HIDAC 75%, and
      prior transplant 30% (33% with R-2). Seven patients could undergo an autologous
      (n = 5) or allogeneic (n = 2) bone marrow/peripheral blood cell transplant after
      one consolidation cycle. Overall survival was 4.2 months, significantly longer in
      responders (complete and partial: median 11 months) than non-responders (p <
      0.001). Median duration of complete remission was 10 months and 2-year
      probability 0.31, but no patient remained disease-free at 3 years. INTERPRETATION
      AND CONCLUSIONS: R-2 was well tolerated, exerted a significant activity in high
      risk AML, and is amenable to further improvements. However, the lack of long-term
      disease-free survivors indicates the need for innovative post-remission
      strategies.

PMID- 9658728
TI  - Use of recombinant granulocyte colony-stimulating factor in Fanconi's anemia.
AB  - BACKGROUND AND OBJECTIVE: Granulocyte colony-stimulating factor (G-CSF) has been
      shown to improve the neutropenic status of patients with bone marrow failure. The
      side effects in prolonged treatment still need to be determined. DESIGN AND
      METHODS: We have studied the efficacy and the long-term side effects of G-CSF in
      four patients with Fanconi's anemia and severe neutropenia. RESULTS: Three
      patients responded with an increase in their absolute neutrophil count; neither
      improvement in platelet count and hemoglobin concentration nor effect on
      transfusion requirements was seen. CFU-GM and BFU-E were undetectable before,
      during and after treatment. Responders showed an important reduction in number
      and severity of infections, with a marked improvement of clinical status. The
      fourth patient developed acute myeloid leukemia after 4 weeks of G-CSF treatment.
      During maintenance, one patient was treated with G-CSF for 18 months, until she
      received bone marrow transplantation, without presenting side effects. In the
      second responding patient G-CSF treatment was stopped because of appearance of
      immature cells in peripheral blood and myeloid blasts in bone marrow. The third
      responding patient presented immature peripheral myeloid cells during the third
      year of G-CSF treatment: disappearance of immature cells was observed after G-CSF
      reduction. In two cases FISH analysis revealed monosomy 7 after G-CSF treatment.
      INTERPRETATION AND CONCLUSIONS: G-CSF use results in an improvement of clinical
      status, but long term administration may cause adverse experiences and requires a
      close hematological monitoring.

PMID- 9658727
TI  - Collection of peripheral blood progenitor cells for autografting with low-dose
      cyclophosphamide plus granulocyte colony-stimulating factor.
AB  - BACKGROUND AND OBJECTIVE: The combination of high or intermediate-dose
      cyclophosphamide (CY) plus granulocyte colony-stimulating factor (G-CSF) is
      useful to mobilize hematopoietic progenitor cells to peripheral blood, but the
      patients require hospitalization. The aim of this study was to evaluate the
      efficiency of low-dose CY plus G-CSF (5 ug/kg/day s.c.) as an outpatient
      treatment in order to collect enough progenitor cells for hematopoietic rescue in
      autologous peripheral blood transplantation (APBSCT). DESIGN AND METHODS: We
      analyzed twenty-eight consecutively treated patients with lymphoma or multiple
      myeloma. The number of CD34+ cells in blood samples was determined from day +7.
      Leukapheresis (LKP) began when the absolute number of CD34+ cells in peripheral
      blood was > 2500/mL and the apheresis product was assayed for mononuclear cells
      (MNC), granulocyte-macrophage colony-forming units (CFU-GM), total nucleated
      cells (tNC) and CD34+ cells. RESULTS: Twenty-eight outpatients with advanced
      hematologic malignancies (13 non-Hodgkin lymphoma, NHL; 10 Hodgkin's disease, HD;
      and 5 multiple myeloma, MM), median age 44 years (range 23-65) received a single
      dose of CY (1.5 g/m2 i.v. day 0) followed by G-CSF (5 ug/kg/day s.c.) from day +1
      to the end of LKP. Considering patients who had successful mobilization (64%), a
      median of 7.1 x 10(6)/kg CD34+ cells (range 3.5-11.9), 5.7 x 10(5)/kg CFU-GM
      (range 1.5-9.2), 4.4 x 10(8)/kg MNC (range 1.9-7.9) were collected. Treatment was
      well tolerated and none of these patients was hospitalized due to neutropenic
      fever. Only one patient received two packed red blood cells following
      chemotherapy. Autologous peripheral blood stem cell transplantation (APBSCT) has
      been performed in 18 patients (64%). The mean number of days to achieve > 0.5 x
      10(9) PMN/L and > 20 x 10(9) PLT/L was 12 (10-17) and 12.6 (8-24), respectively.
      INTERPRETATION AND CONCLUSIONS: Considering a pre-established threshold of 2.5 x
      10(6)/kg CD34+ cells to proceed to APBSCT, the mobilization therapy was
      successful in 64% of the patients but was unsuccessful in 10 patients (5 NHL, 4
      HD and 1 MM). Hematopoietic recovery was complete and stable in all patients. Low
      dose CY plus G-CSF is efficient to collect enough PBSC for hematopoietic rescue
      after myeloablative therapy in patients with lymphoprolipherative disorders or
      multiple myeloma.

PMID- 9658729
TI  - Home treatment of deep vein thrombosis: a two-years experience of a single
      institution.
AB  - BACKGROUND AND OBJECTIVE: Low molecular weight heparin (LMWH) is known to be safe
      and effective for the initial treatment of patients with acute deep-vein
      thrombosis (DVT). Moreover, LMWH allows patients to be treated at home. However,
      only limited data are available on the feasibility of LMWH treatment at home in
      daily clinical practice. DESIGN AND METHODS: We evaluated the feasibility,
      efficacy and safety of home treatment of DVT in a consecutive series of
      outpatients using LMWH over a two year period. The two main reasons for exclusion
      were concomitant pulmonary embolism and a high hemorrhagic risk. Patients were
      treated with 95 IU/kg bid of nadroparin for a minimum of 7 days. The study design
      allowed patients to go home immediately after diagnosis or to be discharged after
      a short hospital stay. Anticoagulation with acenocoumarol was started 2 days
      before discontinuing nadroparin. RESULTS: From 1995 to 1997, 71 consecutive
      outpatients with DVT were treated with nadroparin. Ambulatory treatment was
      feasible in 39 patients (24 patients did not require admission and 15 patients
      were discharged in less than 48 hours). The remaining 32 patients were treated in
      hospital. The main causes for admission were the presence of serious comorbid
      conditions, the severity of symptoms in the involved leg and the inability to
      obtain a diagnosis. None of the patients had clinical recurrent venous
      thromboembolism during the initial treatment with nadroparin. One patient
      receiving nadroparin at home had a non-fatal major bleeding. None of the patients
      to whom the possibility of home therapy was offered wished to remain at hospital.
      However, only 26% of the home-treated patients injected the drug by themselves.
      INTERPRETATION AND CONCLUSIONS: Home therapy of DVT with LMWH bid at doses
      adjusted to patient's body weight is feasible, efficient and safe. Over 50% of
      outpatients with DVT can be treated at home, either entirely or after a short
      stay in hospital. Nevertheless, before using this therapeutic alternative as a
      standard of practice, an adequate assessment of embolic and hemorrhagic risks,
      and comorbid conditions, should be made.

PMID- 9658730
TI  - Prevalence and patterns of symptomatic thromboembolism in oncohematology.
AB  - BACKGROUND AND OBJECTIVE: Approximately 15% of patients with cancer will
      experience a thrombotic episode at some time. Some patients are at particularly
      high risk depending on the histology of the malignant disease. The aim of the
      study was to determine the actual prevalence of thrombotic episodes in
      oncohematologic patients. DESIGN AND METHODS: We conducted a retrospective cohort
      analysis on a total of 515 patients that were admitted to the out-patients clinic
      (Institute of Medical Semeiotics) from January 1, 1986 to January 31, 1996. Two
      main groups were selected for this study: 133 patients suffering from a
      myeloproliferative disorder and 382 patients affected by a lymphoproliferative
      disorder. Follow-up lasted a median of 33 months in both groups (range 3-144
      months). The difference between the observed events for each group was estimated
      by the odds ratio and chi square. Age and sex distribution were estimated by the
      Mann-Whitney test. Distribution of overall survival was estimated by the Kaplan
      Meier method and compared between groups (DVT patients and non DVT patients) by
      the log-rank test. RESULTS: Twenty-three patients experienced a venous thrombotic
      disorder. The prevalence of deep vein thrombosis (DVT) in myeloproliferative and
      lymphoproliferative disorders was 8.27% (n = 11) and 3.14% (n = 12) respectively
      (odds ratio = 0.36; 95% CI = 0.14-0.90; chi-square = 4.94 p = 0.028). DVT was
      apparently idiopathic in 17 cases. In 4 patients another cancer was present; in
      the remaining 2 patients the thrombotic episode was associated with other
      predisposing factors. Although 7 of the 23 patients with DVT died, we cannot find
      any difference in the overall survival compared to oncohematologic patients who
      did not experience DVT. INTERPRETATION AND CONCLUSIONS: The prevalence of
      symptomatic DVT in the oncohematological patients is lower than reported for
      solid tumor. Patients affected by myeloproliferative disease have a higher risk
      of developing thrombosis. DVT if well-treated does not influence the survival of
      oncohematological patients.

PMID- 9658731
TI  - Classification and diagnosis of iron overload.
AB  - BACKGROUND AND OBJECTIVE: Iron overload is the result of many disorders and could
      lead to the development of organ damage and increased mortality. The recent
      description of new conditions associated with iron overload and the
      identification of the genetic defect of hereditary hemochromatosis prompted us to
      review this subject and to redefine the diagnostic criteria of iron overload
      disorders. EVIDENCE AND INFORMATION SOURCES: The material examined in the present
      review includes articles published in the Journals covered by the Science
      Citation Index and Medline. The author has been working in the field of iron
      overload diseases for several years and has contributed ten of the papers cited
      in the references. STATE OF THE ART AND PERSPECTIVES: Iron overload can be
      classified on the basis of different criteria: route of access of iron within the
      organism, predominant tissue site of iron accumulation and cause of the overload.
      Excess iron can gain access by the enteral route, the parenteral route, and
      placental route during fetal life. The different distribution of iron within
      parenchymal or reticuloendothelial storage areas indicates different pathogenetic
      mechanisms of iron accumulation and has relevant implications in terms of organ
      damage and prognosis of the patients. Iron overload may be either primary,
      resulting from a deregulation of intestinal iron absorption as in hemochromatosis
      or secondary to other congenital or acquired conditions. Diagnosis of iron
      overload can be suspected on the basis of clinical data, high transferrin
      saturation and/or serum ferritin values. However, several hyperferritinemic
      conditions are not related to iron overload, but may imply severe disorders
      (inflammations, neoplasia) or a deregulation of ferritin synthesis (hereditary
      hyperferritinemia-cataract syndrome), and iron overload secondary to
      aceruloplasminemia, and the recently described dysmetabolic-associated liver iron
      overload syndrome, are characterized by low or normal transferrin saturation
      levels. Liver biopsy is still very useful in the diagnostic approach to iron
      overload disorders, by defining the amount and the distribution of iron within
      the liver. The analysis of HFE gene mutations (C282Y and H63D) is a simple and
      strong tool in the diagnostic work out of iron overload conditions.

PMID- 9658732
TI  - Molecular genetics and control of iron metabolism in hemochromatosis.
AB  - BACKGROUND AND OBJECTIVES: Hereditary hemochromatosis (HC) is an inborn error of
      iron metabolism that leads to progressive iron overload. Considerable advances in
      the knowledge of molecular events in iron metabolism have been recently obtained.
      These molecular findings, the cloning of the gene responsible for HC (HFE gene)
      and the results of preliminary studies on the HFE protein prompted us to review
      this topic. INFORMATION SOURCES: The material examined in this review article
      includes papers and abstracts published in the Journals covered by the Science
      Citation Index and Medline. The authors have been working in the field of HC for
      several years and have contributed eleven of the quoted papers. STATE OF ART AND
      PERSPECTIVE: HC is now recognized as the genetic disease characterized by the
      homozygosity for the Cys-->Tyr substitution at position 282 (C282Y) of the HFE
      protein. The mutation abolishes the association of the HFE protein with beta 2
      microglobulin (beta 2M), making the complex unable to gain the cell surface. Thus
      HC is an example of abnormal trafficking of the corresponding proteins. It is
      clear by the analysis of its structure that HFE protein is not an iron
      transporter itself, but has a regulatory role in iron metabolism. Its peculiar
      localization in the crypt cells of the small intestine suggests an important role
      in iron trafficking at this level. However, other proteins are involved in iron
      uptake, as the recently cloned Nramp2, the first iron transporter discovered in
      mammalians. Nramp2 has a recognized role both in the intestinal iron uptake and
      in the iron transport within the erythroblast. The relationships between HFE and
      Nramp2 are still unexplored. The recent association of HFE gene with transferrin
      receptor (TfR) in trophoblast cells opens new possibilities on its role in
      cellular iron uptake. The existence of other forms of genetic iron overload
      suggests that the scenario of iron proteins is not yet fully defined. Further
      studies in this field will contribute to our knowledge of iron metabolism
      regulation in humans.

PMID- 9658733
TI  - Human herpesvirus-8 in hematological diseases.
AB  - The huge amount of experimental and clinical observations supporting the possible
      involvement of human herpesvirus 8 (HHV-8) or Kaposi sarcoma herpesvirus (KSHV)
      in human lymphoproliferative diseases was critically reviewed during a workshop
      organized by the Italian Society for Experimental Hematology in Florence, Italy,
      on July 3rd, 1997. The organizers have prepared this report for the readers of
      Haematologica.

PMID- 9658734
TI  - T-cell acute lymphoblastic leukemia occurring in a patient with acute
      promyelocytic leukemia.
AB  - Secondary acute lymphoblastic leukemia (sALL) following acute myeloid leukemia
      (AML) is a rare event; only eight cases have been reported. We report a patient
      with acute promyelocytic leukemia (APL), in hematological and molecular remission
      who developed T-ALL three years after the diagnosis of APL. The morphological,
      cytochemical, phenotypical and molecular features of this T-ALL were different
      from those of the previous APL. The absence of t(15;17), negative PML/RAR alpha
      at reverse transcription polymerase chain reaction (RT-PCR) analysis and presence
      of TcR delta support the hypothesis that the T-ALL in this sALL case originated
      from a different clone from that of the APL cells.

PMID- 9658735
TI  - The magic of immersion oil: gray platelet syndrome.

PMID- 9658736
TI  - The number of nucleoli expressed by the nucleolar coefficient in the
      granulopoietic bone marrow compartment in non-leukemic persons and patients
      suffering from chronic myeloid leukemia.

PMID- 9658737
TI  - Autologous stem cell transplantation in multiple myeloma: a single center
      experience.
AB  - This study shows the feasibility and safety of autologous stem cell
      transplantation in 32 of 98 multiple myeloma patients referred to our institution
      over a 3-year period. Complete response rate was 19% and partial response rate
      58%. A significantly better outcome was shown among newly diagnosed patients in
      comparison with pretreated patients.

PMID- 9658738
TI  - Enzyme replacement therapy decreases hypergammaglobulinemia in Gaucher's disease.
AB  - We report the effects of enzyme replacement therapy in a patient with Gaucher's
      disease associated with a monoclonal gammopathy. Alglucerase induces a linear
      decline in immunoglobulin and beta 2-microglobulin levels. This observation
      suggests that this treatment decreases the chronic antigenic stimulation commonly
      found in Gaucher's disease.

PMID- 9658739
TI  - The standard of disclosure in human subject experimentation.

PMID- 9658740
TI  - Criminalization of perinatal HIV transmission.

PMID- 9658741
TI  - Improper expert medical testimony. Existing and proposed mechanisms of oversight.

PMID- 9658742
TI  - Medicinal use of marijuana. Is the debate a smoke screen for movement toward
      legalization?

PMID- 9658743
TI  - Evaluation of pancreatic exocrine function and zinc absorption in alcoholism.
AB  - Zinc absorption in alcoholism was studied by a combination of zinc tolerance
      tests in 382 male patients with alcoholism (more than 140 g/day of ethanol) who
      had alcohol-induced disease of the liver or pancreas. In study 1, the serum zinc
      level was measured in all patients, and serum zinc and fecal chymotrypsin levels
      were compared in various disease groups. In study 2, 14 patients with liver
      cirrhosis (LC), 15 with chronic pancreatitis (CP), 7 with LC + CP, and 7 controls
      underwent oral zinc tolerance and zinc dipicolinate tolerance tests, zinc
      absorption and disorders of pancreatic exocrine functions were examined. In study
      1, the serum zinc concentration was significantly lower in the CP and LC groups
      than in the control group, and the fecal chymotrypsin activity was significantly
      lower in the CP than in the control groups. In study 2, during the oral zinc
      tolerance test, the serum zinc concentration 3 hours after administration was
      significantly lower in the LC, CP and LC + CP groups than in the control group.
      In these groups, the serum zinc concentration was significantly lower in the
      abnormal fecal chymotrypsin group than in the control group at 2 and 3 hours
      after administration of zinc sulfate. In the oral zinc dipicolinate tolerance
      test, the serum zinc levels 2 and 3 hours after administration were significantly
      elevated in the control and all disease groups; there were no significant
      differences between the control and each disease group. These results suggest
      that reduction of pancreatic exocrine functions by alcohol and chronic reduction
      of synthesis of ligands such as picolinic acid in the liver are involved in the
      reduction of serum zinc in alcoholism.

PMID- 9658744
TI  - Cyfra 21-1 as a marker of lung cancer.
AB  - The utility of cytokeratin fragment (Cyfra) 21-1, a new tumor marker, was
      investigated in 100 patients with lung cancer. Sandwich enzyme immunoassay
      detected Cyfra 21-1 in the sera of 60% of patients. Sensitivity of this marker
      was especially high (86.4%) for squamous cell carcinoma, exceeding that of a
      similar marker, squamous cell carcinoma antigen (SCC, 54.5%). In contrast,
      sensitivity of Cyfra 21-1 was relatively low for adenocarcinoma (52.6%) and for
      small cell carcinoma (50%). We conclude that Cyfra 21-1 is of value in diagnosis
      of lung cancer, particularly squamous cell carcinoma.

PMID- 9658745
TI  - Type IV collagen and laminin enhance the motility, adhesion, and proliferation of
      hepatoma cells.
AB  - Type IV collagen and laminin, major components of the basement membrane, are
      involved in several biologic activities. In malignant tumors, cell-matrix
      interactions are very important for tumor invasion and metastasis. In
      hepatocellular carcinoma, these matrices are present around hepatoma cells.
      However, there is little known how these matrices influence on the behavior of
      hepatoma cells. In this study, we investigated the participation of type IV
      collagen and laminin in the motility, adhesion, and proliferation of hepatoma
      cells using three different human hepatoma cell lines (KYN-1, 2, 3). The
      production of type IV collagen and laminin was investigated by immunoelectron
      microscopy. The effects of type IV collagen and laminin on hepatoma cell
      migration, adhesion, and proliferation were evaluated by the haptotactic
      migration assay, phagokinetic track assay, an adhesion assay, and a 3H-thymidine
      incorporation assay. Immunoelectron microscopy showed the production of type IV
      collagen and laminin by hepatoma cells. Type IV collagen and laminin enhanced
      haptotactic migration, chemokinesis, adhesion, and thymidine incorporation by
      hepatoma cells. The combination of type IV collagen and laminin had the most
      pronounced effects on these biologic activities. These results indicate that type
      IV collagen and laminin promote hepatoma cell motility, adhesion, and
      proliferation in an autocrine manner, suggesting enhancement of invasion and
      metastasis of hepatoma cells by these basement membrane components in vivo.

PMID- 9658746
TI  - EMG analysis of the lower extremities during pitching in high-school baseball.
AB  - I evaluated the contractions of the muscles of the lower extremities during
      baseball pitching using video imaging and simultaneous surface EMG. The subjects
      were 10 members of a high school baseball club and, for contrast, 10 students
      without any baseball club experience. I divided their pitching movements into two
      phases determined with respect to the landing of the non-pivot leg. The EMG
      signal intensities over the 2 seconds prior to landing, and over the 2 seconds
      after landing, were then integrated to give an EMG value to each phase. I then
      computed this value as the % MMT. The abductor and adductor of the hip muscles of
      both lower extremities in the players were strongly contracted, especially the
      adductor. This finding was consistent with the observation that pitching tends to
      lead to adductor muscle disorders. Strengthening the adductor and its antagonist
      abductor can therefore directly influence the capability for pitching, and can
      reduce the risk for the adductor disorders.

PMID- 9658747
TI  - Induction of apoptosis in ovarian carcinoma cell line by gonadotropin-releasing
      hormone agonist.
AB  - Gonadotropin releasing hormone (GnRH) agonist suppresses the growth of the cancer
      cells in vitro. To evaluate the effect of a GnRH agonist (GnRHA) in ovarian
      carcinomas, we investigated the interactions of GnRHA with the KOC-2s human
      ovarian cancer cells. The addition of GnRHA (10(-8)-10(-6)M) produced an increase
      20-30% in the number of cells (p < 0.05). GnRHA (10(-5) M) produced a slight,
      statistically insignificant decrease of < 10% in the cell count. No DNA
      fragmentation was produced by GnRHA (10(-8)-10(-6)M). However, GnRHA (10(-5)M)
      produced internucleosomal cleavage of DNA into fragments with multiples of 180 to
      200 bp. This DNA "ladder" pattern is characteristic of apoptosis. The amount of
      Fas antigen was reduced by each concentration of GnRHa. The addition of GnRHA
      (10(-6)M and 10(-5)M) significantly increased the secretion of TNF-alpha (p <
      0.001). The time- and dose-dependent effects of GnRHA might be confined to the
      KOC-2s cells as demonstrated by growth inhibitions and characteristic
      internucleosomal DNA fragmentation. However, the effects of GnRHA on secretion of
      TNF-alpha and the expression of Fas antigen differed. The present results provide
      a basis for future studies on the mechanism of apoptotic effect of GnRHA.

PMID- 9658748
TI  - Increased circulating levels of interleukin-1 receptor antagonist in patients
      with inflammatory bowel disease.
AB  - Plasma levels of interleukin-1 receptor antagonist (IL-1ra), a potent inhibitor
      of IL-1, were measured in patients with inflammatory bowel disease. Plasma IL-1ra
      levels in patients with active ulcerative colitis and Crohn's disease were higher
      than in normal controls. No significant difference was noted in plasma IL-1ra
      concentrations between active ulcerative colitis and Crohn's disease patients.
      The levels in patients with inactive disease were lower than in active patients,
      but were higher than in normal controls. Plasma IL-1ra levels correlated
      significantly with clinical disease activity and laboratory parameters such as C
      reactive protein or leukocyte count. In conclusion, circulating IL-1ra in
      patients with inflammatory bowel disease may be a useful marker of disease
      activity.

PMID- 9658749
TI  - Negative-strand HCV RNA was not detected in bone marrow cells of patients with
      HCV infection.
AB  - To determine whether hepatitis C virus (HCV) replicates in bone marrow, we
      investigated positive- and negative-strand HCV RNA in bone marrow cells and
      fluids, and sera from patients with HCV infection. The study population consisted
      of 15 patients positive for antibodies to HCV (anti-HCV). Positive- and negative
      strands HCV RNA were detected using highly strand-specific rTth reverse
      transcription-polymerase chain reaction (rTth RT-PCR) followed by Southern
      blotting analysis. Positive-strand HCV RNA was detected in 12 (80%) serum
      samples, in 13 (86.7%) bone marrow fluid specimens, and in 6 (40.0%) bone marrow
      cell samples. Negative-strand HCV RNA was detected in 9 (60.0%) serum samples, 11
      (91.7%) fluid specimens, while it was not detected in bone marrow cells. The
      absence of negative-strand HCV RNA in bone marrow cells suggested that HCV does
      not replicate in these cells. Negative-strand HCV RNA detected in serum and bone
      marrow fluid samples may have been due to contamination with circulating HCV RNA
      from hepatocytes.

PMID- 9658750
TI  - Effect of laser irradiation for residual lesions of early gastric carcinoma after
      endoscopic mucosal resection.
AB  - Endoscopic mucosal resection (EMR) for mucosal gastric carcinoma without lymph
      node metastases has been widely accepted as a curative procedure in Japan. We
      consider patients with elevated type well-differentiated adenocarcinoma less than
      20 mm in size, as well as those with depressed type intramucosal carcinoma
      without ulcer and less than 10 mm in size, to be absolute indications for
      treatment by EMR. In this study, we evaluated 26 patients (68.4 +/- 9.7 yrs) with
      absolute adaptive lesions who underwent EMR as an initial treatment, resulting in
      incomplete resection of lesions. We performed laser therapy on patients with
      residual lesions, and examined the effects of this treatment. Eighteen cases with
      elevated type lesions (90%) have not exhibited recurring lesions treated by
      initial laser therapy alone following EMR over a period of 24 months. However,
      among patients with depressed type lesions, only 1 (16.7%) did not experience
      recurrence. There was a significant difference between the two groups (p <
      0.001). These recurring lesions were treated by additional laser therapy. The
      results were more satisfactory in patients with elevated type lesions (95.5%)
      than in patients with depressed type lesions (80%). No patient died of gastric
      cancer during follow-up. Endoscopic laser irradiation is useful in treating
      patients with residual lesions after EMR.

PMID- 9658751
TI  - Microsurgical management of craniopharyngiomas--outcomes in 56 patients.
AB  - Fifty-six patients with craniopharyngiomas were operated by microsurgical
      techniques during a 20-year period. Of the 56 patients, 28 were males and 28 were
      females, with a mean age of 33 years (range 1 to 78 years). Twenty patients
      (35.7%) were less than 15 years of age. Remission was defined as clinical
      improvement with stable ophthalmological and neurological status, CT and/or MRI
      evidence of a decrease in tumor size or tumor disappearance when a patient was
      discharged from hospital. Ineffectiveness was defined as lack of change in the
      preoperative clinical status. The mean follow-up period in this study was 6.9
      years, with 11 patients monitored. The most common presentation was visual
      dysfunction (69.6%). 33.9% of the patients presented with headache. The most
      frequent preoperative finding was a visual field defect, with 55.4% of the
      patients so affected; 39.5% of patients had preoperative hypothyroidism and 40%
      had hypoadrenalism. Diabetes insipidus was found preoperatively in 7.1%. Three
      female patients had amenorrhea. Hydrocephalus was uncommon, being present in only
      10.7%. Unruptured aneurysms were found incidentally in 2 cases. A pterional
      approach was used in 29 patients (52%), a transcallosal approach in 13 (23%), a
      transcortical approach and a transsphenoidal approaches in 3 (5%), and a lamina
      terminalis approach in 1 patient. Multiple procedures were required in 8 patients
      in order to provide significant relief of compressive symptomatology. Overall,
      12.5% of the tumors were completely resected. 92.9% of our patients were in
      remission, 2 had ineffectiveness result, and 2 died of postoperative
      complications. Except for the completely resected cases, all the other patients
      underwent radiotherapy postoperatively. The results of this series show that
      microsurgical management of craniopharyngiomas yields good operative results.

PMID- 9658752
TI  - Changes of visual performance induced by exposure to whole-body vibration.
AB  - To clarify the effects of whole-body vibration (WBV) on visual performance,
      visual acuity and a self-rated assessment of difficulties in visible perception
      were determined after various frequencies of vibration in six healthy males. Two
      different sitting postures, an erect posture and a muscle-relaxed posture, were
      used. Sinusoidal vertical vibrations at ten frequencies (8, 10, 12.5, 16, 20, 25,
      31.5, 40, 63.5 and 80 Hz) were applied to the seated subjects for 20 sec. The
      magnitude of acceleration at each vibration frequency was maintained at 2.5 msec
      2 (r.m.s.). The visual performance was evaluated by a standard visual acuity test
      and a self-rated assessment for difficulties in visible perception. The
      disturbances of visual performance were dependent on the vibration frequency (p <
      0.01, ANOVA) with a maximum reduction of visual acuity at a frequency of 12.5 Hz.
      The disruption of the visual performance was more severe with the erect posture
      than with the muscle-relaxed posture. In conclusion, short-term WBV exposure can
      affect visual performance, depending on the vibration frequency and the sitting
      posture. The visual acuity and self-rated assessment of disturbances of vision
      may be influenced by the resonance frequency of the eyeball.

PMID- 9658753
TI  - Therapeutic implications of interleukin-10 in inflammatory bowel disease.
AB  - Enhanced production of proinflammatory cytokines has been described in
      inflammatory bowel disease. The effect of interleukin (IL)-10, a cytokine with
      antiinflammatory activity, or anti-IL-10, on cytokine production by cultured
      colonic mucosa or blood mononuclear cells from patients with active inflammatory
      bowel disease was evaluated. Addition of IL-10 to the culture medium of colonic
      tissues or blood mononuclear cells resulted in inhibition of both IL-1 beta and
      tumor necrosis factor-alpha production and augmentation of IL-1 receptor
      antagonist production. Conversely, neutralization of endogenous IL-10 was found
      to augment both tumor necrosis factor-alpha and IL-1 beta production and inhibit
      IL-1 receptor antagonist production. In addition, the production of IL-10 by
      mononuclear cells was suppressed by prednisolone. In conclusion, IL-10 and
      related molecules may be useful in the treatment of inflammatory bowel disease.

PMID- 9658754
TI  - Myeloperoxidase concentrations in the stool as a new parameter of inflammatory
      bowel disease.
AB  - Neutrophils play a predominant role in inflammatory and immune reactions in
      inflammatory bowel disease. It is well established that the level of
      myeloperoxidase, a constituent of neutrophil azurophil granules, reflects the
      number of neutrophil. We examined the usefulness of determining stool levels of
      myeloperoxidase in patients with inflammatory bowel disease. Myeloperoxidase
      levels in stool extracts were measured using a radio-immunoassay in 33 patients
      with ulcerative colitis, 32 with Crohn's disease, 9 inflammatory disease controls
      and 15 normal controls. Stool levels of myeloperoxidase in active inflammatory
      bowel disease patients increased significantly, and correlated with laboratory
      parameters and endoscopic grade of inflammation. A paired analysis showed a
      decrease in myeloperoxidase levels after the resolution of disease exacerbation.
      These results suggest that stool myeloperoxidase is a simple, noninvasive, and
      relevant marker of disease activity.

PMID- 9658755
TI  - Impact loading on the foot and ankle and its attenuation during level walking.
AB  - We studied impact loading on the foot and ankle at heel strike during level
      walking. Cadaveric testing was carried out on a skin-mounted accelerometer to
      estimate the bone or joint impact, and gait analysis was performed to evaluate
      the impact on the foot and ankle and its attenuation during level walking.
      Simulation using a rigid-body model estimated the impulse at landing during level
      walking. The skin-mounted accelerometer showed the same tendency as the bone
      mounted accelerometer in cadaveric testing. In the gait analysis, impact at the
      calcaneus was attenuated at the medial malleolus and was less attenuated with the
      ankle fixation. In the simulation, impact became greater if the foot and ankle
      functions were eliminated. These results suggest that the foot and ankle are
      directly involved in attenuating the impact at heel strike during level walking.

PMID- 9658756
TI  - Evaluation of third generation anti-HCV test kit (SYNPEP HCV-EIA II) using sera
      of inhabitants from HCV hyperendemic area.
AB  - We examined the characteristics and usefulness of a third generation anti-HCV
      test kit, SYNPEP HCV-EIA II (Kyokuto Pharmaceutical Inc., Tokyo, Japan). The sera
      of inhabitants from a hepatitis C virus (HCV) hyperendemic area were used. The
      kit had even or more anti-HCV detection sensitivity and reproducibility than
      ORTHO HCV III ELISA Test System (Ortho-Clinical Diagnostic K.K., Tokyo, Japan) or
      HCV PHA 2nd Generation (Dinabot Co., Ltd., Tokyo, Japan). SYNPEP HCV-EIA II
      needed less total reaction time than other EIA kits, resulting in a simple
      procedure. Also, HCV RNA was detected in 90% of subjects who had a 7.5 or greater
      cut-off index (COI) of SYNPEP HCV-EIA II kit. In conclusion, SYNPEP HCV-EIA II
      require cheap cost and simple procedure and it could be applied to mass screening
      to find out HCV RNA positive persons who may need clinical care.

PMID- 9658757
TI  - Usefulness of magnifying endoscopy for diagnosing tumorous lesions of the
      colorectum.
AB  - The usefulness of magnifying endoscopy was assessed by examining the extent to
      which a magnifying endoscope can provide images of pits and by analyzing the
      consistency of the pit patterns visualized by magnifying endoscopy with the pit
      patterns visible under a stereomicroscope. Study materials consisted of 83 cases
      of tumorous colorectal lesions. Under a magnifying endoscope, pits were visible
      across the entire surface of the lesion in 46 (55.4%) of the 83 cases. The pit
      pattern visualized by magnifying endoscope in 32 (69.6%) of the 46 cases was
      identical to the pattern observed under a stereomicroscope. Of various pit
      patterns, type IIIs (tubular, round pit that is smaller than normal pit), type
      IIIL (tubular, round pit that is larger than normal pit) and type IV (dendritic,
      gyrus-like type pit) were relatively well visualized under a magnifying
      endoscope. It was difficult to obtain images of type V (irregular or amorphous
      pit) with a magnifying endoscope. It seems therefore easy to distinguish tumors
      from non-tumorous lesions using a magnifying endoscope. This imaging technique
      may provide information more useful for the diagnosing tumorous colorectal
      lesions and selecting therapeutic strategy, if staining methods and mucus
      removing methods are improved.

PMID- 9658758
TI  - Diagnosis of colorectal tumor invasion by endoscopic miniature probe
      ultrasonography.
AB  - We evaluated the diagnostic efficacy of high-frequency (20 MHz) ultrasound probe
      (HFUP) for the staging of invasive depth of colorectal tumors. The subjects were
      27 patients with colorectal tumorous lesions who were treated by endoscopic or
      surgical operation (11 patients with lesions remaining in the mucosa, 13 patients
      with submucosal cancer, and 3 patients with cancer invading the muscularis
      propria or deeper layers). Considering the previous reports that endoscopic
      mucosal resection (EMR) is indicated in cases of tumors remaining in the mucosa
      or cancer slightly invading the submucosal layer, we divided the submucosal layer
      vertically into three equal areas (most superficial, middle and deepest areas
      which were referred to as sm1, sm2 and sm3, respectively). The depth of tumor
      invasion in histological specimens was compared to the depth of tumor invasion as
      assessed preoperatively using the HFUP. The HFUP-based diagnosis was identical to
      the histological diagnosis in 86.4% of all cases, when the depth of tumor
      invasion was rated on a three-point scale: (i) m-sm1, (ii) sm2-sm3 or (iii) mp or
      deeper. These results indicate that the HFUP is very useful in selecting a
      therapeutic method for colorectal tumors.

PMID- 9658759
TI  - Clinical aspects of cryptogenic hepatocellular carcinoma.
AB  - Clinical features of hepatocellular carcinoma in 22 patients without serum HBsAg,
      HBV DNA, anti-HCV antibody and HCV RNA were characterized and possible pathogenic
      factors for this cryptogenic hepatocellular carcinoma were prospectively
      assessed. Twenty-two patients were selected from 434 patients with hepatocellular
      carcinoma (HCC) who were treated at the Second Department of Internal Medicine,
      Kurume University Hospital between January 1994 and December 1996. Serum samples
      collected from these patients were all negative for HBsAg, HBV DNA, anti-HCV
      antibody, and HCV RNA. Patients were evaluated based on past history, present
      illness, history of habitual alcohol consumption, results of the serological and
      biochemical laboratory tests at diagnosis of HCC, Anti-HBc antibody,
      autoantibodies, GBV-C/HGV RNA, and histopathologic findings of non-cancerous
      portion of the liver were also evaluated. Among 22 patients with non-B non-C HCC,
      16 patients (72.7%) had a history of alcoholic liver disease, 6 patients had an
      infection of schistosomiasis Japonica, and 1 patient had Budd-Chiari syndrome.
      Nine patients (40.9%) were positive for anti-HBc antibody, but their titers were
      low in all cases. Among 22 patients, positive for auto antibody, 7 patients
      (31.8%) were positive for anti-nuclear antibody, and 17 patients (77.3%) were
      positive for anti-smooth muscle antibody. Only 1 patient was positive for GBV
      C/HGV RNA. Histopathologic examination was performed in 3 cases for non-cancerous
      portions of the liver. Liver cirrhosis and liver with passive congestive fibrosis
      were diagnosed in 2 cases each. The remaining one case showed normal feature of
      the liver. In conclusion, the majority of the 22 patients with non-B non-C HCC
      had a history of alcoholic liver disease. Many were also positive for auto
      antibodies. These results suggest that patients with alcoholic liver disease or
      hepatic disease with autoantibodies may be defined as the high-risk group of
      developing non-B non-C HCC and should be periodically underwent a complete
      medical examination.

PMID- 9658760
TI  - Relationship between Lens culinaris agglutinin reactive alpha-fetoprotein and
      biological features of hepatocellular carcinoma.
AB  - Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3), which
      is a fucosylated variation of AFP, is not only sensitive and specific for
      localization of hepatocellular carcinoma (HCC) but also a prognostic factor for
      patients with HCC. The relationship between status of AFP-L3% in serum and
      pathological findings was studied using 48 resected HCC specimens. AFP-L3
      fraction was measured by lectin-affinity blotting using an AFP Differentiation
      Kit L (Wako, Osaka, Japan), and was expressed as AFP-L3% (AFP-L3/total AFP x
      100%). A cut-off level of 15% was used. Pathological findings of HCC such as
      histological grade (well, moderately and poorly differentiated HCC), vascular
      invasion, and Ki67 (MIB1), p53 (DO7) and alpha-catenin immunohistochemical
      staining were studied. According to the results of serum AFP concentrations and
      AFP-L3%, the 48 patients were divided into the following three groups: AFP
      greater than or equal to 20 ng/ml and AFP-L3 positive (group A, n = 14), AFP
      greater than or equal to 20 ng/ml and AFP-L3 negative (group B, n = 14) and AFP
      less than 20 ng/ml (group C, n = 20). Ki67 labeling index of HCC tissue in group
      A was 27.8 +/- 18.9%, which was significantly higher than those of group B (9.6
      +/- 10.1%, p < 0.024) and group C (11.1 +/- 11.2%, p < 0.03). In group A, p53
      expression was higher and alpha-catenin staining was reduced significantly
      compared with those of group B or C, respectively. The results of the study
      suggest that the proportion of AFP-L3% in serum reflects some biological features
      of HCC.

PMID- 9658761
TI  - Metastatic model of human colon cancer constructed using orthotopic implantation
      in nude mice.
AB  - Nude mice have been used to grow subcutis (s.c.) growing human colorectal tumors,
      but these tumors rarely metastasize. This is a problem for studies into the
      biological behavior of metastatic subpopulations of human colorectal cancers. We
      have followed the evolution of the parental line and of a variant of human colon
      carcinoma KM12 cells, that were both tumorigenic, following implantation into the
      s.c. or cecal wall of nude mice. The tumors growing s.c. did not produce visceral
      metastases, whereas the cecal tumors metastasized to the regional mesenteric
      lymph nodes and to the liver. However, the incidence of liver metastases was
      different between the parental cell line KM12C cells and the in vivo selected
      cell line KM12SM cells after orthotopic inoculation. The morphological findings
      of KM12 cells proliferating in a monolayered sheet revealed that these two cell
      lines consisted of various cell populations. These results suggest that in the
      orthotopic colon cancer models, liver metastasis is defined by difference in
      subpopulations of metastatic phenotypes to the liver with early dominance of its
      growth in the implanted organ. As a result, our new model using orthotopic
      implantation of KM12SM cells, which produce a 50% incidence of liver metastasis,
      can help to provide a technique to study the biological behavior of metastatic
      subpopulations of human colon cancers.

PMID- 9658762
TI  - A metastasis to the nasal tip from a cervical carcinoma--a case report.
AB  - Metastases to the nasal tip from gynecological malignancies are extremely rare.
      We present a case of a tumor metastatic to the nasal tip from a carcinoma of the
      uterine cervix. We administered high-dose focal irradiation to the site of the
      tumor. The literature on metastases to the nose, maxillary sinuses, and paranasal
      sinuses from gynecologic malignancies is reviewed.

PMID- 9658763
TI  - Angiodysplasia of the stomach confirmed by endoscopy and selective angiography-
      report of a case.
AB  - Gastric angiodysplasia that caused continuous gastrointestinal bleeding is
      reported in a 75-year-old woman who had been treated with repeated blood
      transfusions because of severe anemia. Endoscopic examination was performed and
      revealed a bright-red lesion on the anterior wall of the upper gastric body.
      Injection therapy was performed at first, but the follow-up endoscopy showed a
      recurrent red lesion in same place. Selective angiography revealed a dense stain
      suggestive of a hypervascular lesion, measuring about 1 cm in diameter. Partial
      gastrectomy including resection of the lesion was performed. During a follow-up
      period of more than 12 months, there was no sign of recurrence of bleeding.

PMID- 9658764
TI  - A case of giant leiomyosarcoma of the rectum.
AB  - A 63 year-old-man was admitted to our hospital with the chief complaint of
      dyschezia. Digital examination revealed a large solid mass on the posterior wall
      of the rectum. Endoscopically, the tumor was covered by an intact mucosal layer.
      Under the diagnosis of rectal leiomyosarcoma, abdominoperineal resection of the
      rectum was performed. The tumor was 10 x 9 x 8 cm in size, and its cross section
      showed a gray-white tumor with central necrosis. Microscopically, the large tumor
      of the rectum was mainly located in the proper muscle layer and adventitia, and
      showed cellular proliferation of spindle-shaped and mild pleomorphic stromal
      cells, arranged in interlacing fashion, and focal necrosis. The histologic
      findings support the diagnosis of leiomyosarcoma. Leiomyosarcoma of the rectum is
      a relatively uncommon disease. We report our case with reference to the
      literature.

PMID- 9658765
TI  - Treatment of bile leaks from cystohepatic and common hepatic duct after
      laparoscopic cholecystectomy.
AB  - Laparoscopic cholecystectomy is widely accepted by patients and physicians
      despite the lack of controlled trials comparing this technology with conventional
      cholecystectomy. The cystohepatic ducts represent accessory bile ducts of
      variable size which frequently travel within the gallbladder fossa or in the
      posterior wall of the gallbladder. These ducts can be injured during laparoscopic
      cholecystectomy and can result in bile collection if transected. Recently, we
      have experienced two cases of injury to the bile duct during operation. One case
      was a transection of the accessory bile duct, the other one was an injury to the
      common hepatic duct. We present herein the clinical course of the two cases, in
      which biliary leakage, following laparoscopic cholecystectomy, was successfully
      managed by the end to end anastomosis of the bile duct.

PMID- 9658766
TI  - A case of invasive lobular carcinoma of the breast.
AB  - A 43-year-old woman presented to our department with left breast lump, measuring
      10 mm x 10mm x 6mm. On physical examination and mammography, the lump was
      suspected to be due to mastopathy, but malignancy could not be excluded based on
      ultrasonography. Excisional biopsy showed that it was an invasive lobular
      carcinoma. A modified radical mastectomy was performed after obtaining informed
      consent. She remained disease-free seven years after surgery.

PMID- 9658767
TI  - Clinicopathological features of intraorbital neurinoma--report of two cases.
AB  - Clinicopathological features of intraorbital neurinomas were investigated in two
      patients. Magnetic resonance imaging (MRI) findings in Case 1 were similar to
      those in Case 2. The central region of the neurinomas showed a slightly high
      intensity area with a marginal low intensity on T1-weighted images (T1WI),
      whereas on T2-weighted images (T2WI), the central area of the tumor was very low
      intensity with a marginal high intensity area. After gadolinium-DTPA (Gd-DTPA)
      injection, these areas were homogeneously enhanced in both cases. The deference
      in enhancement after Gd-DTPA injection reflected the distribution of cellularity
      and vessels in the tumor.

PMID- 9658768
TI  - Three cases of the giant gastric leiomyosarcomas.
AB  - We report three cases of giant gastric leiomyosarcoma. Diagnosis was made prior
      to surgery using various diagnostic modalities. The patients were two women (77
      and 77 years old) and one man (40 years old) whose chief complaints were
      abdominal pain, anorexia, and tarry stool. All patients presented with a large
      palpable mass in their upper abdomen at the time of admission. Based on
      characteristic findings from a gastric barium study, computed tomography (CT),
      and angiography, the patients were diagnosed as having gastric leiomyosarcomas
      displaying extramural growth. In the first case, a patient received a total
      gastrectomy, while local resection was performed in the second case because of
      pedunculated extragastric development. In the third case, total gastrectomy was
      combined with splenectomy and resection of the pancreatic tail. Twenty-two months
      after the original operation, the first case had multiple liver metastases. We
      present the three cases here, and review the literature.

PMID- 9658769
TI  - A case of chronic hepatitis C with sinus bradycardia during IFN therapy.
AB  - The patient was a 55-year-old male with no history of heart diseases. He was
      administered recombinant IFN alpha-2b under the diagnosis of chronic hepatitis C.
      Since sinus bradycardia (heart rate 40 bpm) appeared in the fourth week of
      administration (cumulative dose; 240 M.U), IFN was discontinued. Bradycardia was
      resolved 1 week after discontinuation of IFN, and the treatment was resumed with
      a change of the regimen to IFN-beta. Since no bradycardia was noted thereafter,
      IFN therapy could be completed (total dose; 108 M.U). These observations suggest
      that the type of IFN or total dose contributed to the appearance of
      cardiotoxicity.

PMID- 9658770
TI  - A simplified method of calculating an overall goodness-of-fit test for the Cox
      proportional hazards model.
AB  - Gronnesby and Borgan (1996) propose an overall goodness-of-fit test for the Cox
      proportional hazards model. The basis of their test is a grouping of subjects by
      their estimated risk score. We show that the Gronnesby and Borgan test is
      algebraically identical to one obtained from adding group indicator variables to
      the model and testing the hypothesis the coefficients of the group indicator
      variables are zero via the score test. Thus showing that the test can be
      calculated using existing software. We demonstrate that the table of observed and
      estimated expected number of events within each group of the risk score is a
      useful adjunct to the test to help identify potential problems in fit.

PMID- 9658771
TI  - Acute middle ear infection in small children: a Bayesian analysis using multiple
      time scales.
AB  - The study is based on a sample of 965 children living in Oulu region (Finland),
      who were monitored for acute middle ear infections from birth to the age of two
      years. We introduce a nonparametrically defined intensity model for ear
      infections, which involves both fixed and time dependent covariates, such as
      calendar time, current age, length of breast-feeding time until present, or
      current type of day care. Unmeasured heterogeneity, which manifests itself in
      frequent infections in some children and rare in others and which cannot be
      explained in terms of the known covariates, is modelled by using individual
      frailty parameters. A Bayesian approach is proposed to solve the inferential
      problem. The numerical work is carried out by Monte Carlo integration (Metropolis
      Hastings algorithm).

PMID- 9658772
TI  - On tests for group variation with a small to moderate number of groups.
AB  - This paper considers a family of penalized likelihood score tests for group
      variation. The tests can be indexed by a measure of degrees of freedom. At one
      extreme, with degrees of freedom one less than the number of groups, is the usual
      score test for a fixed effects alternative using indicator variables for the
      groups, while at the other extreme, in the limit as the degrees of freedom-->0,
      is a test closely related to a score test based on a random effects alternative.
      Asymptotic power comparisons are made for the tests in the family. As would be
      expected, different members of the family are more efficient for different
      alternatives. Generally the tests with smaller degrees of freedom appear to have
      better power than the standard test for alternatives focusing on differences
      among the larger groups, and lower power for alternatives focusing on differences
      among the smaller groups. Simulations indicate the asymptotic approximation to
      the distribution performs better for the tests with small degrees of freedom.

PMID- 9658773
TI  - Adjusting and comparing survival curves by means of an additive risk model.
AB  - Survival curves may be adjusted for covariates using Aalen's additive risk model.
      Survival curves may be compared by taking the ratio of two adjusted survival
      curves; the ratio is denoted the generalized relative survival rate. Adjusting
      both survival curves for all but one of a common set of covariates gives the
      partial relative survival rate, which measures the covariate-specific
      contribution to the generalized relative survival rate. The generalized and
      partial relative survival rates have interpretations similar to the traditional
      relative survival rates frequently used in cancer epidemiology. In fact, the
      traditional relative survival rate can be generalized to a regression context
      using the additive risk model. This population-adjusted relative survival rate is
      an alternative and useful method for removing confounding effects of age,
      cohorts, and sex. The authors use a data set of malignant melanoma patients
      diagnosed from 1965 to 1974 in Norway. The 25-year survival of 1967 individuals
      is studied.

PMID- 9658774
TI  - Estimating lifetime and age-conditional probabilities of developing cancer.
AB  - Lifetime and age-conditional risk estimates of developing cancer provide a useful
      summary to the public of the current cancer risk and how this risk compares with
      earlier periods and among select subgroups of society. These reported estimates,
      commonly quoted in the popular press, have the potential to promote early
      detection efforts, to increase cancer awareness, and to serve as an aid in study
      planning. However, they can also be easily misunderstood and frightening to the
      general public. The Surveillance, Epidemiology, and End Results (SEER) Program of
      the National Cancer Institute and the American Cancer Society have recently begun
      including in annual reports lifetime and age-conditional risk estimates of
      developing cancer. These risk estimates are based on incidence rates that reflect
      new cases of the cancer in a population free of the cancer. To compute these
      estimates involves a cancer prevalence adjustment that is computed cross
      sectionally from current incidence and mortality data derived within a multiple
      decrement life table. This paper presents a detailed description of the
      methodology for deriving lifetime and age-conditional risk estimates of
      developing cancer. In addition, an extension is made which, using a triple
      decrement life table, adjusts for a surgical procedure that removes individuals
      from the risk of developing a given cancer. Two important results which provide
      insights into the basic methodology are included in the discussion. First, the
      lifetime risk estimate does not depend on the cancer prevalence adjustment,
      although this is not the case for age-conditional risk estimates. Second, the
      lifetime risk estimate is always smaller when it is corrected for a surgical
      procedure that takes people out of the risk pool to develop the cancer. The
      methodology is applied to corpus and uterus NOS cancers, with a correction made
      for hysterectomy prevalence. The interpretation and limitations of risk estimates
      are also discussed.

PMID- 9658775
TI  - A nonparametric estimator of survival functions for arbitrarily truncated and
      censored data.
AB  - It is well-known that the nonparametric maximum likelihood estimator (NPMLE) may
      severely under-estimate the survival function with left truncated data. Based on
      the Nelson estimator (for right censored data) and self-consistency we suggest a
      nonparametric estimator of the survival function, the iterative Nelson estimator
      (INE), for arbitrarily truncated and censored data, where only few nonparametric
      estimators are available. By simulation we show that the INE does well in
      overcoming the under-estimation of the survival function from the NPMLE for left
      truncated and interval-censored data. An interesting application of the INE is as
      a diagnostic tool for other estimators, such as the monotone MLE or parametric
      MLEs. The methodology is illustrated by application to two real world problems:
      the Channing House and the Massachusetts Health Care Panel Study data sets.

PMID- 9658776
TI  - [An epidemic of hemorrhagic fever with renal syndrome in Croatia in 1995].
AB  - In the spring of 1995, the largest outbreak of hemorrhagic fever with renal
      syndrome (HFRS) so far was recorded in Croatia. There were 125 patients reported
      to the National Croatian Institute of Public Health, Department of Epidemiology.
      The disease occurred simultaneously in several localities, some of them close to
      the previously known natural foci (Mala Kapela, western Slavonia); the focus on
      Dinara was newly discovered. War circumstances in Croatia were closely related to
      this outbreak. There were 50 patients hospitalized in the University Hospital of
      Infectious Diseases in Zagreb; 5 of them were civilians from Zagreb area and 45
      soldiers (Mala Kapela 33, Dinara 7, western Slavonia 5). In all patients the
      disease was serologically proven (in 6 by indirect immunofluorescence method and
      in 44 by ELISA-test). Both previously known types of viruses--Hantaan and Puumala
      were diagnosed in each locality. In general, the illness was more severe in
      patients with Hantaan virus infection. Two patients died, the illness was severe
      in 25, moderately severe in 11 and mild in 12 patients. For the first time
      inflammatory lung changes were recorded in 13 out of 37 (35.1%) patients who were
      examined by X-ray in the early stage of the disease.

PMID- 9658777
TI  - [War injuries of the arteries].
AB  - The experience with military vascular injuries in the recent war in Crotia is
      reviewed. From April 1991 to October 1995, 197 wounded persons with 231 injuries
      of arteries were admitted to the University Hospital Rebro. The most common
      injuries were of lower extremity arteries (54.5%), and the most frequent method
      of repair was revascularisation with saphenous vein graft interposition.
      Fasciotomies were performed in 34% because of frequent associated injuries of
      bones (34.5%) and veins (46.7%). In 20.7% casualties pseudoaneurysms and
      arteriovenous fistulas were found. Postoperative thrombosis (9%) was a
      consequence of local infection, massive necrosis and sepsis. Amputation rate was
      7.7%, and mortality 5.3%. These results are very satisfactory in comparison with
      the results in literature. This is a result of good organization of our war
      surgical service: rapid transportation of wounded persons to convenient surgical
      centres and high surgical skill.

PMID- 9658778
TI  - [Improvement of sanitation conditions in the liberated Croatian regions after the
      "Storm" campaign--the Lika-Senj County example].
AB  - More than 6,000 sq km of the central and southern areas of the Republic of
      Croatia were liberated by the Storm campaign, August 4-7, 1995. On August 8,
      1995, the Ministry of Health sent expert teams to the newly liberated areas, in
      order to ensure the basic conditions for the displaced persons to return and live
      there. To describe the public health measures taken we used the example of the
      Lika-Senj County (3,746 sq km and 71,215 population). Until October 1, 1995, 50
      bodies, killed in action, were detected, pathologically and forensically
      examined, and then buried. Two hundred and thirty-three mostly elderly and sick
      persons were admitted to the reception center in Gospic; 93 of them returned to
      their homes, 133 were accommodated with their relatives and friends, and seven
      were referred for treatment (four of them died). Two hundred and ten cattle
      carcasses were buried using adequate sanitation measures, whereas 5,575 sheep,
      3,138 head of horned cattle, 298 head of hoofed animals and 300 head of other
      cattle were caught alive. The procedures of disinfection, disinfestation and
      disodoration were performed in 720 apartments, 2 hotels, 3 schools, one
      kindergarten, one health care unit, one sports hall and 5 shops. The main water
      pump was cleared of mines and partially repaired, whereas some 20 water supply
      objects were placed under surveillance. Three food depots were found and properly
      treated. The entire territory was closely observed for a possible occurrence of
      infectious diseases.

PMID- 9658779
TI  - [Disseminated pulmonary ossification. Case report].
AB  - Metaplastic pulmonary ossification is usually described as dendriform or nodular
      in patients with chronic inflammatory lung disease or long-standing pulmonary
      edema. We present a case of dendriform pulmonary ossification found accidentally
      at autopsy in a 66-year old man. In addition, some of the theories relating to
      the development of this rare phenomenon are discussed.

PMID- 9658780
TI  - [Echinococcal pulmonary cyst with multiple fistulization into the bronchi].
AB  - The case of a 10 year old boy with an hydatid pulmonary cyst was presented. The
      cyst multiply fistulated into the bronchus. The preoperative diagnostic pathway,
      the operative treatment and complete postoperative recovery was described.

PMID- 9658781
TI  - [Case report of a female patient with autoimmune hemolytic anemia and cold
      agglutinin antibodies].
AB  - We report a case of acute transient cold agglutinin disease, the etiology of
      which we could not determine with the available methods. Cold autoagglutinins had
      anti I specificity, high titers of the autoantibody (> 1:1,000) and the thermal
      range was relative wide. Our patient had severe haemolysis and immunosuppressive
      therapy with methylprednisolone and cyclophosphamide was administered. It is a
      question how much these immunosuppresive agents influenced the recovery, and in
      what extent it was a self limited disease with spontaneous recovery.

PMID- 9658782
TI  - [Use of intraoperative ultrasound in neurosurgery].
AB  - Intraoperative ultrasound (US) is a device which is a great help to neurosurgeon
      in intracerebral lesions localization, in the definition of inner tumors
      structure, in its relation to the surrounding structures, as well as during
      stereotaxic operations. We report our experiences with US in more than 500
      operations. Its maximum usage is during gliomas and metastases operations because
      of their subcortical localization. Choosing this optimal approach to the tumor,
      the surrounding brain is minimally damaged. Using modern devices we are able to
      distinguish edema from infiltrative gliomas, which was not possible using former
      devices (both edema and gliomas are hyperechoic). In vascular neurosurgery we use
      US mostly in the localization of small arteriovenous malformations (AVMs). In
      pediatric neurosurgery the usage is very often in drainage operations for
      ventricular catheter placement control. The main US shortage is lower image
      resolution, and the basic advantage is real time imaging. It enables our prompt
      intervention in every unfavorable situation.

PMID- 9658783
TI  - [A model for monitoring drug prescribing in general practice].
AB  - When prescribing drugs, general practitioners at the same should satisfy the
      requirements of medical science and their vocation, being aware of their task of
      a rational disposal of the limited resources allocated for health care. The aim
      of the paper was to determine the characteristics of monitoring model for drug
      prescription in general practice, taking into consideration the characteristics
      of the population, morbidity, drugs and physicians. A prospective monitoring of
      prescribing drug during one month was carried out in six doctor's offices of
      general practice/family medicine at the Dugave-Travno Health Station of the Novi
      Zagreb Health Center. In processing data on patients, drugs and physicians the
      following were used: distribution description and analysis, pair's tests and
      General Factorial Anova. Out of 3397 patients who visited the above mentioned
      doctor's offices, 2320 (68.3%) patients were prescribed 4796 prescriptions--an
      average of 2.07 prescriptions per patient (from 2.00 to 2.42). The total cost of
      drug prescription was 360,117.33 kunas (from 43,632 to 77,910 kunas). The number
      of prescriptions and the cost of prescribed drugs increased significantly in
      terms of statistics with the age of patients (Spearman's correlation coefficient
      0.2263; p < 0.001). By General Factorial Anova statistically significant
      difference was determined in the cost variable among the physicians with the
      impact of covariate age and number of prescriptions. Professionally, the most
      appropriate and most rational prescribing was observed among physicians who had
      the highest educational level and the longest experience in practice. In order to
      analyze and assess the appropriatness of drug prescription in general practice,
      the first essential step is to collect data on what is being prescribed, for whom
      it is being prescribed, and to enable access to data for physicians. This paper
      has indicated some of the characteristics of a monitoring model for drug
      prescription in general practice. Formulation and implementation of this model
      would considerably promote the professional appropriateness and rationality in
      drug prescription in general practice.

PMID- 9658784
TI  - [First page].

PMID- 9658785
TI  - [The desire for information and informed consent in general anesthesia].
AB  - BACKGROUND: In the last years the interest for Informed Consent (IC) in
      anaesthesia has been growing and it has been debated on the adequate explanations
      in order to obtain a consent. The purpose of the present study was to assess
      patients' desire for information about anaesthesia. METHODS: In this prospective
      study a form has been given to consecutive patients waiting for surgical
      operation in general surgery or ear nose throat surgery and able to read and
      write, to inform them about the necessity of General Anaesthesia (GA); they were
      asked to complete a questionnaire concerning their desire for information about
      the following six items concerning anaesthesia: "the duration of anaesthesia";
      "what type of pain will I have when I come round, and what pain-killers will I be
      given"; "details on the various types of anaesthesia, how and where will I be
      anaesthetized"; "what are the most common complications of general anaesthesia";
      "where and how will I come round from general anaesthesia"; "what is artificial
      respiration in general anaesthesia". RESULTS: 107 patients participated in the
      study, 24 of whom were undergoing surgery for malignant cancer and 83 for benign
      non-oncological diseases. More than two-thirds of patients expressed their wish
      to receive information, and the trend of desire to know was inversely related to
      age (p < 0.05). There was no significant statistical difference in the desire to
      know according either to sex or to the kind of disease (benign or malignant). The
      demand for information about pain was particularly high (85%), also in the older
      group of patients. The results and the difficulties for obtaining IC are debated.
      CONCLUSIONS: The growth of patients' desire for information about anaesthesia is
      an aspect of the evolving doctor-patient relationship in Italy. Efforts should be
      directed at improving reciprocal communication.

PMID- 9658786
TI  - [The effect of anesthesiologic technique on the mental state of elderly patients
      submitted for orthopedic surgery of the lower limbs].
AB  - Influence of anesthetic technique on mental status in elderly patients submitted
      to major orthopedic procedures of lower limbs. Mental impairment is a common
      occurrence in elderly patients after major orthopedic surgery. Few studies have
      been published so far on this topic in spite of its relevant clinical and
      economic implications. OBJECTIVE: 1) To verify whether anesthesia has a causative
      role in postoperative mental confusion in elderly patients; 2) to compare the
      effects of General Anesthesia (GA) and Spinal Anesthesia (SA) on mental status.
      DESIGN: Controlled, comparative study. PATIENTS: Sixty patients aged > or = 70,
      ASA I-II, submitted to femoral neck repair. SETTING: Anesthesia Dept. and
      Orthopedic Dept. of a District Hospital in Italy. METHOD: The day before surgery
      the mental status of elected patients was evaluated employing a modified Organic
      Brain Syndrome (OBS) scale (Gustafsson). The better the mental status, the lesser
      the OBS score. It was possible therefore to distinguish "oriented" from "confuse"
      patients (38 vs 22) if they scored < or = 6 or > 6 respectively. Patients from
      each group were than randomly assigned to receive either GA or selective SA.
      Neither group was premedicated. GA was induced with propofol 1 mg/kg and
      maintained with O2/N2O 40/60% and isoflurane; atracurium was employed to
      facilitate mioresolution. Spinal anesthesia was performed with hyperbaric 1%
      bupivacaine. All patients were monitored in the Recovery Room (RR) for at least
      one hour. Occurrence of hypotension and/or hypoxia in the Operating Room (OR) or
      the RR was immediately treated. Mental status was reassessed on the 1st and 2nd
      postoperative day and results were compared with the corresponding preoperative
      OBS scores both in GA patients and in SA patients. RESULTS: No statistically
      significant differences were found between pre- and postoperative OBS scores in
      both GA and SA group, whether "oriented" or "confuse". CONCLUSIONS: Mental status
      of elderly patients submitted to femoral neck repair doesn't seem to be
      influenced by the anesthetic technique chosen, independent of preoperative
      psychic conditions.

PMID- 9658787
TI  - [Evaluation of psychological characteristics in the preoperative phase of
      patients with mental retardation].
AB  - OBJECTIVES: To make easier the psychological evaluation of patients affected by
      Mental Retardation and scheduled for general anesthesia. DESIGN: A form prepared
      by the Psychological Service of the IRCCS "Oasi Maria SS" in collaboration with
      the Service of Anesthesia was evaluated prospectively. The form is addressed to
      relatives and psychologists; the interviewed person is firstly asked for a short
      description of patient's personality and for any suggestion useful to patient's
      management; secondly it is requested to assign a score from 1 (never present) to
      5 (always present) to 44 items concerning adaptive capacities (divided into body
      scheme, spoken language, receptive language, mimic-gestural language, temporal
      orientation, memory), emotional and social fields (including sensibility,
      dependence, and social behaviors), problematic and stereotyped behaviors.
      SETTING: A medical and psychological Institute aimed at the study of Mental
      Retardation. PATIENTS: Twenty-five patients affected by Mental Retardation and
      scheduled for general and dental surgery. RESULTS: The form supplied a great deal
      of information and suggestions for patient management. Subjects that did not
      cooperative with the anesthetist presented lower scores about the ability to use
      mimic-gestural language (p < 0.05) and higher scores about the presence of
      anxiety or fear caused by the sight of syringes or blood (p < 0.05) and about
      behaviors of flight, isolation, or aggression caused by fear (p < 0.05). By
      contrast, patients presenting mild or moderate degrees of Mental Retardation
      differentiated from patients with serious degree of Mental Retardation about body
      scheme (p < 0.001), spoken language (p < 0.05), receptive language (p < 0.001),
      temporal orientation (p < 0.001) and memory (p < 0.001). CONCLUSIONS: The form
      was very useful to plan patient management. These data suggest that the lack of
      cooperation by some patients affected by Mental Retardation is related to fear,
      anxiety, and incapacity to communicate rather than to the degree of Mental
      Retardation.

PMID- 9658788
TI  - [The recurrence of hepatitic C in orthotopic liver transplantation].
AB  - BACKGROUND: This study is a review of hepatitis C recurrence in patients
      undergoing an orthotopic liver transplantation (OLT); to verify how many patients
      HCV-positive before OLT confirm a persistent viremia after OLT and how many with
      viremia show hepatitis histological evidence. METHODS: Thirty consecutive
      patients, 24 males, median age 52.5 underwent OLT for posthepatitic C cirrhosis
      since January 1993 in the "Transplantation Center" of Genoa. Serology included
      anti-HCV search, HCV-RNA and HBV-DNA determinations, biopses were performed in
      the transplanted liver within the month after operation, subsequently at every
      hepatic enzymes increase. RESULTS: Twenty-one patients are currently alive,
      median follow-up of 14.5 months. Before OLT anti-HCV antibodies search was
      positive in all the patients while the HCV-RNA by PCR resulted positive in 17 and
      negative in 4. Before OLT the HBV-DNA in patients with associated hepatitis B was
      negative. After OLT 5 patients, of the 17 HCV-RNA positive before OLT, have
      turned negative then all became again positive from 6 to 12 months later; 2 of
      the 4 patients HCV-RNA negative before OLT have turned positive, and remained
      still negative two with hepatitis C associated with hepatitis B. Although viral
      replication was present in 95% of the patients, clinical and histological
      evidence of recurrence was ascertained only in 29%. CONCLUSIONS: It should be
      noted that the hepatitis histological picture doesn't correspond to a severe
      worsening of clinical conditions, an evolution justifying transplantation. The
      long-term results of this therapeutic choice are still uncertain due to the high
      incidence of recurrences.

PMID- 9658789
TI  - [Therapy of articular and periarticular pain with local anesthetics (neural
      therapy of Huneke). Long and short term results].
AB  - OBJECTIVE: Assessment of the outcomes on the articular and periarticular pain of
      the knee, by a reflexotherapy with local anesthetics, denominated also
      neuraltherapy. EXPERIMENTAL DESIGN: Retrospective observational study with 3
      years' follow-up. ENVIRONMENT: An Ambulatory Center for Pain Management.
      PATIENTS: All the patients (N = 115) with knee pain treated with neuraltherapy in
      the period 1982-31 August 1996 (retired patients 2, mean age 68 +/- 15.2 years in
      the remaining). INTERVENTIONS: The employed reflexotherapy, denominated also
      neuraltherapy by Huneke, uses a local anesthetic (prevalently lidocaine) in 0.5
      1% concentration and small quantity (0.5-1 ml for point) on tender/trigger and/or
      acupuncture points, as well as in anatomical structures like articulations,
      nerves, arteries or veins. The number of sessions has been of 7.03 +/- 3.3.
      OUTCOME MEASURES: Outcomes are evaluated in terms of percentage subjective
      improvement of the pain at the end of the therapy and at 1-3-6 months, 1-2-3
      years, and then divided in 5 groups (no improvement-fair-good-very good
      excellent). RESULTS: At the end of the therapy the improven cases were the 91.2%,
      the 83.7% at 1 month, the 64.6% at 3 months, the 41.3% at 6 months, the 22.5% at
      1 year, the 12.1% at 2 years and the 7.9% at 3 years. CONCLUSIONS: These outcomes
      suggest a good effectiveness of this treatment in the painful diseases of the
      knee, but further randomised double-blind trials are necessary.

PMID- 9658790
TI  - [Muscular enzyme level disorders and a malignant hyperthermia susceptability
      test: postoperative study of a patient with elevated CPK].
AB  - The preoperative evaluation of the enzymatic level concerning the functioning of
      the neuromuscular system, is of particular importance. The diseases of these
      regions may lead to Malignant Hyperthermia (MH) in the course of general
      anaesthesia. The authors illustrate the case of a young asymptomatic patient with
      constantly high levels of CPK, who was later affected by Central Core Disease
      (CCD), a rare hereditary slow progressing myopathy strictly related to MH. The
      authors suggest tat preoperative CPK levels, though not predictive of a patient
      to develop MH, can allow identification of patients affected by clinically silent
      myopathies. This can also acquire legal importance in case of clinical MH
      manifestation.

PMID- 9658791
TI  - [Streptococcus pyogenes and resistance to macrolides: experience at Monza].

PMID- 9658792
TI  - [Early treated congenital hypothyroidism. Evaluation of school learning].
AB  - BACKGROUND: The aim of this paper was to evaluate school learning in early
      treated CH children in order to investigate whether and how this pathology
      influences school performance. METHODS: Using a sample of 50 early treated CH
      children who have received regular follow-up at our Institute, 20 subjects
      attending primary (grade) school or the final year of nursery school for
      assessment of school learning have been selected. Results were compared with a
      class/grade matched control group. Evaluations of cognitive, motor and language
      development, T4 level determined at birth, thyroid disorder and socio-cultural
      level of the family background were examined in relation to the school
      performance of each child. RESULTS: The evaluations showed that out of 20 CH
      children, 5 (25%) presented generalized learning disorders. This percentage is
      higher than in the normal population (3.4%). When learning disorder findings were
      correlated with data pertaining to motor, speech and cognitive development, socio
      cultural level and thyroid disorder, it was found that children with generalized
      learning difficulties presented more severe motor and speech disorders, a lower
      intelligence quotient and a lower socio-cultural background than children
      achieving higher scores in school tests. CONCLUSIONS: The conclusion is drawn
      that early treated CH children of same age have more learning difficulties during
      nursery school, while they have normal learning performances during primary
      school.

PMID- 9658793
TI  - [Adolescents with scoliosis: psychological and psychopathological aspects].
AB  - BACKGROUND: The present study focuses on psychological and psychopathological
      aspects in children and adolescents with scoliosis. METHODS: The case series
      included 28 subjects with scoliosis (7 males, 21 females; range 9-25 years; mean
      age 15.8 years) admitted to the Dept. of Orthopaedics of Gaslini Institute and
      referred to our observation. Psychological approach included semi-structured
      interviews focused on the evolution of scoliosis and based on questions about
      consciousness of illness, family and patient emotional reactions during
      treatment; familial, social and school adaptation; body image; onset of
      psychopathological disorders. Family relational and educational attitudes were
      also considered. The following psychological tests were also performed: Raven
      Progressive Matrices; "Draw-a-Person" test; Sacks' battery of incomplete
      sentences to evaluate cognitive aspects, body image, familial and social
      relationships, interactive aspects. RESULTS: During adolescence consciousness of
      illness appeared concomitantly with the beginning of treatment. Most subjects
      presented intellectual-relational compensation strategies, but in a reasonable
      number of cases they showed insecurity and inferiority feelings. On a conscious
      level, body image appeared normal in most cases, but unconsciously (in 45% of
      cases) there were anguish aspects related to feelings of body deterioration.
      During long-term treatments anxious reactions, sometimes temporary, (in 36% of
      cases) and depressive aspects (in 9% of cases) were observed. CONCLUSIONS: The
      results obtained stress the importance of the family and the medical staff in
      providing a reassuring and firm support, in order to face difficulties related to
      the patient's illness.

PMID- 9658794
TI  - [Descriptive analysis of measles epidemic in Palermo, from September 1996 to June
      1997. Failure of a vaccination campaign].
AB  - BACKGROUND: The authors report 1642 measles cases observed from September 1996 to
      June 1997 at the "G. Di Cristina" Children's Hospital. 34% of patients were
      hospitalized at the Division of Infectious Diseases. METHODS: The records of
      children admitted with measles to emergency area were retrospectively collected.
      The medical records (anamnestic, clinical and laboratory findings) of
      hospitalized children were obtained from schedules which since 1993 were
      performed to perspectively collect the exanthematous diseases. International
      criteria for the definition of measles case were applied. The variables
      considered were: background, demographic data, seasonal distribution, clinical
      presentation, complications and days of hospital stay. RESULTS: The results of
      this research showed that the outbreak involved predominantly infants. The
      complications accounted for 72% of measles hospitalized cases. Four cases of
      encephalitis were observed. A total of 1692 days of hospital stay was reported.
      CONCLUSIONS: These data show the failure in measles control adopted by the
      Sicilian Region and confirm the difficulties to achieve high percentage of
      parents participation to the infant recommended vaccination program.

PMID- 9658795
TI  - [Microcytosis. A hematological characteristic common to diverse diseases].
AB  - The pathological conditions characterized by microcytosis are reviewed and their
      pathophysiological mechanisms also at the molecular level are described. Moreover
      clinical, haematological and laboratory findings for differential diagnosis are
      discussed. Finally, the most efficacious schedules for the treatment of iron
      deficiency anaemia are reported.

PMID- 9658796
TI  - Human herpesvirus-7 DNA in cerebrospinal fluid.
AB  - An infection by HHV-7 with presence of virus DNA in the spinal fluid was
      ascertained in a twenty five month old boy with an epileptic syndrome shortly
      after birth. The child was frequently admitted to hospital due to his basal
      disease and frequent bacterial infections. In the occasion of one of these
      hospital admissions for bacterial infections in conjunctiva, spleen and a lung,
      virological investigations were also carried out disclosing the presence of HHV-7
      DNA in a sample of spinal fluid and of serum and the absence of DNAs from the
      other herpesviruses. The patient's monitoring for HHV-7 showed the presence of
      HHV-7 DNA in a sample of serum and in various samples of peripheral blood
      lymphocytes and saliva, but not in the cerebrospinal fluid sample successive to
      that positive for HHV-7 DNA. Forty seven days before the diagnosis of HHV-7
      infection, the patient received a human gamma-globulin therapy which obscured the
      humoral response mounted against the virus by the host, so, whether the HHV-7
      presence in the central nervous system was associated with a primary or a
      reactivated infection remained uncertain. The absence of detectable HHV-7 serum
      IgM antibody, however, suggests the HHV-7 DNA finding on the occasion of a virus
      reactivation rather than a primary infection. The virological data suggest that
      HHV-7 may have possibly reached the central nervous system in the course of a
      viremia. The absence of HHV-6 and HHV-7 antibodies, present in the patient's
      serum at a high level, support the integrity of the blood-brain barrier. A
      possible pathogenetic role of HHV-7 in the child's disease seems unlikely, since
      the epileptic syndrome was pre-existing.

PMID- 9658797
TI  - Teenage births in the United States: state trends, 1991-96, an update.
AB  - OBJECTIVES: This report provides State-specific birth rates for teenagers for
      1991 and 1996 and the percent change, 1991-96. METHODS: Tabular and graphical
      description of trends in teenage birth rates by age group for each State.
      RESULTS: Birth rates for teenagers 15-19 years declined significantly in all but
      three States between 1991 and 1996. Declines by State ranged from 6 to 29
      percent.

PMID- 9658799
TI  - [Detection of extracellular matrix protein (laminin) in experimental arterial
      anastomoses].
AB  - AIM: To investigate the distribution of Laminin in experimental microvascular
      surgery. MATERIAL AND METHODS: Autografts (4 mm) of the left common carotid
      artery in 20 Wistar rats were harvested after 4 weeks. The specimens were
      investigated immunohistochemically for the demonstration and distribution of
      Laminin. RESULTS: The demonstration and distribution pattern of Laminin was a
      function of the accuracy of each single suture. In the intima, the organisation
      and amount of Laminin was directed to the lumen and dependent from the distance
      and vitality of the vessel segments' cells. The media had in its axis direction
      the lowest reparative potency to regenerate the continuity break. The adventitia
      formed a thick cuff around the anastomosis, which was circularly grown through
      with Laminin-positive vasa vasorum. The marked myointimal hyperplasia in the area
      around the anastomosis and in the entire autograft was constituted of Laminin
      positive extracellular matrix. CONCLUSIONS: Our results support the demand for a
      careful and atraumatic suture technique in microvascular surgery.

PMID- 9658800
TI  - [Nager syndrome].
AB  - In this publication, Nager syndrome was analyzed in the literature and six
      patients from our clinic were evaluated in relation to symptoms, etiology and
      pathogenesis. The diseases to be considered when making a differential diagnosis
      are pointed out. Clarification of the etiology is still pending. Molecular
      genetic research in these patients is possibly the key for new findings. A case
      report illustrates the results of interdisciplinary treatment by the surgeon and
      orthodontist. Possibilities and problems in relation to therapy are demonstrated.

PMID- 9658801
TI  - [Extrafollicular variant of centrally located adenomatoid odontogenic tumor].
AB  - An adenomatoid odontogenic tumor has been reported which was not connected with
      any impacted or displaced tooth. The clinical and radiographical results were
      consistent with a non-odontogenic cyst, but in this case the pathohistological
      examination revealed string-like and partly cross-linked cells of odontogenic
      epithelium as well as solid aggregates of epithelia, possessing gland-like
      structures at their centers. Furthermore, small deposits of PAS-positive
      materials could be seen which could be interpreted as non-mineralized dentine
      with a tubular basic structure. The therapy consisted of completely enucleating
      the tumor. Any recurrence of malignant degeneration has not yet been reported.

PMID- 9658802
TI  - [Prospective study of the pathology of radiation-induced mucositis].
AB  - One of the most severe early side effects of radiation in head and neck cancer
      patients is mucositis. Inflammation of the oral mucose may lead to an extreme
      subjective burden, restricting the patients' well-being and even leading to an
      interruption of radiotherapy. The aim of our prospective study was to investigate
      the pathological alterations of the oral mucosa during irradiation. Therefore,
      samples from head and neck cancer patients were taken before radiation and a 30-G
      and a 60-G radiation dose. Pathogenetic alterations were determined by
      immunohistochemical staining of various cell surface molecules known to be
      involved in the pathogenesis of inflammation. Staining was performed with
      antibodies against ICAM 1, VCAM 1, ELAM, 25F9, 27E10, and RM3-1. Our study
      demonstrates the expression rates of the various surface molecules during
      inflammation. Expression of RM3-1 and ICAM 1 showed a steep increase during the
      time of radiation, whereas expression of ELAM reached a low constant value.
      Therefore, we conclude that distinct cell surface molecules demonstrate a
      characteristic time-dependent expression during radiation. Better insight into
      the pathogenesis of radiation-induced mucositis may help to develop a
      pathological classification of mucositis and to improve therapeutic strategies.

PMID- 9658803
TI  - [Effect of the diameter of various bore holes on retention of osteosynthesis
      screws].
AB  - The standard drill size for most osteosynthesis screws is about 75% of the
      screw's external diameter. When screws are inserted in thick cortical bone, a
      small pilot hole size can result in high torsional stress, leading to screw
      fracturing. The aim of this study was to enlarge the drill size up to a critical
      pilot hole size, exceeding of which leads to a rapid decrease of the screw's
      holding power. Titanium screws of diameter 1.5 and 2 mm were inserted in discs of
      PVC, wood and porcine mandibular bone with different thickness between 2 to 4 mm,
      using pilot hole sizes of 66-95% of the screw's external diameter. The maximum
      torque was recorded and pull-out tests were performed. Ten trials were conducted
      for each screw-pilot hole size-material combination, yielding a total of 1560
      tests. A multiphase regression analysis was performed to calculate the critical
      pilot hole size (CPHS). In torque measurements, the CPHS of microscrews were
      between 83% and 85% of screw outer diameter (SOD) and the CPHS of miniscrews were
      between 80% and 90% of SOD. In pull-out analysis the CPHS of microscrews were
      between 83% and 89% of SOD and the CPHS of miniscrews were between 79% and 91% of
      SOD. The CPHS was thus found to be around 85% of the screw's external diameter.
      Up to this critical point the pilot hole size may be increased without affecting
      the holding power of the screws.

PMID- 9658804
TI  - [Confocal laser scanning microscopy (CLSM) for validation of non-destructive
      histotomography of healthy bone tissue].
AB  - OBJECTIVES: Fixation (formalin), decalcification (sections) or mechanical
      treatment (grinding) all bear the risk of artifacts occurring during hard-tissue
      histology. Because studies on the etiology of pathological changes mostly focus
      on subclinical lesions, artifacts can simulate early changes or even be
      superimposed on existing changes. The objective of this study was to determine
      how artifacts can be reduced. MATERIAL AND METHODS: In confocal laser scanning
      microscopy (CLSM) a focused laser beam scans the surface of the specimens and
      penetrates into the tissue. The intensity of the remitted light is recorded. The
      confocal effect is due to an extremely small aperture (pin-hole), excluding light
      from out-of-focus planes of the sample. By stepwise movement of the object table,
      a tomographic series of tomographic images is obtained. Sound cortical bone
      samples of the lower jaw (n = 20) were studied by light microscopy and by CLSM,
      visualizing identical areas of a ground sectioned sample after H&E staining.
      Additionally, embedded and fresh blocks of tissue of the same bone sample were
      studied histotomographically in the CLSM. RESULTS: (1) Light microscopic
      micromorphology of cortical bone can be visualized adequately in the CLSM; (2)
      many structures that can be visualized by light microscopy only after special
      staining (e.g., osteozyte processes) can be visualized by the CLSM using sample
      blocks without pretreatment. CONCLUSION: (1) Nondestructive subsurface
      histotomography by CLSM totally excludes mechanical artifacts; (2)
      physicochemical artifacts can be handled more easily because fresh samples can be
      studied; (3) pseudo-three-dimensional imaging allows histological interpretation
      of the tissue that is equivalent to macroscopic tomographic techniques (CT, MRT).

PMID- 9658805
TI  - [Experiences with distraction osteogenesis in therapy of severe peripheral airway
      obstruction in infancy and early childhood].
AB  - Children with craniofacial malformations are at special risk for the development
      of peripheral airway obstruction. The problems are magnified in patients with
      retroposition or hypoplasia of the mandible. In these cases, the base of the
      tongue is posteriorly displaced, hereby decreasing the airway diameter. By
      application of distraction osteogenesis the mandible can be lengthened to move
      the base of the tongue forward and open the airway. Three female patients aged
      between 7, 11, and 15 months suffering from peripheral airway obstruction caused
      by mandibular hypoplasia were treated by gradual distraction. All of them had a
      gastrostomy or a nasogastral tube in place, respectively, due to severe nutrition
      problems. In the youngest patient tracheostomy was performed shortly after birth
      and was already planned in the 15-month-old child, who had received a permanent
      nasopharyngeal tube. The 11-month-old child suffered from severe refractory sleep
      apnea. Exercises in oral feeding were possible in the youngest patient after 10
      days of distraction. In the oldest one, the airway tube was removed on the six
      day of distraction and, thus, tracheotomy was successfully avoided. In the 11
      month-old child apneic events a rapidly decreased. Our experience suggests that
      distraction osteogenesis after careful preoperative evaluation can be
      successfully performed for the treatment of peripheral airway obstruction in
      patients with selected craniofacial anomalies.

PMID- 9658806
TI  - [Cranial and cervical chordomas. A differential diagnostic problem].
AB  - Cranial and cervical chordomas can spread by para- or retropharyngeal extension
      up to the region of the salivary glands or the jaw and may simulate a tumor of
      the salivary glands or jaw. In occasional cases, because the tumors often expand
      slowly, months or years may pass between the first clinical symptoms and
      diagnosis. Diagnostic problems exist in differentiating these chordomas from
      pleomorphic adenoma, mucinous carcinoma, or chondrosarcoma. Ten relevant
      observations of typical cranial and cervical chordomas (Salivary Gland Register
      Hamburg 1965-1996) were analyzed more closely by pathohistological and
      immunohistochemical means. The exact diagnosis is based upon the evidence of
      blown-up, bubble-like ("physaliform") cells which contain mucus drops in a
      vacuolized cytoplasm and are surrounded by extensive areas of mucoid mucus. The
      pattern of immunohistochemistry is characterized by the multifold expression of
      cytokeratin, vimentin, and EMA. The differential diagnosis is discussed with
      reference to further types of chordoma (chondroid chordoma, dedifferentiated
      chordoma with spindle cell sarcomatous transformation), chondrosarcoma,
      pleomorphic adenoma, and mucus-producing carcinoma.

PMID- 9658807
TI  - [Differential giant cell epulis diagnosis--malignant melanoma of the mouth
      mucosa].
AB  - Malignant melanoma of the oral mucosa is a rare tumor. The clinical image can
      vary, so that diagnostic errors are possible. The case of a primary malignant
      melanoma camouflaging a giant cell granuloma is presented. The importance of
      biopsy and histological diagnosis is underlined.

PMID- 9658808
TI  - [Malignant epithelioid schwannoma of the inferior alveolar nerve.Case report with
      review of the literature].
AB  - Malignant epithelioid schwannoma is a very rare disease originating from the
      Schwann cells. It is a subtype of malignant schwannoma. The limbs are the main
      location of this entity. In our case study, the inferior alveolar nerve was
      involved in the mandible. The prognosis for patients with this disease is poor,
      because metastasis occurs in more than 50%. Clinical and histological features
      and treatment in a 42-year-old man are discussed in detail. In addition, a short
      review of the literature and treatment recommendations are given.

PMID- 9658810
TI  - [Craniofacial abnormalities in the Charite Virchow Collection].
AB  - On 27 June 1899 Rudolf Virchow (1821-1902) inaugurated the Museum of Pathology at
      the Charite Hospital. The collection comprised 23,500 pathologic-anatomical
      specimens. Most of the collection was destroyed in World War II. About 2000
      samples were saved. Meanwhile the stock has increased to about 9000 objects. The
      development, contents and structure of the famous Virchow Collection are
      described with special reference to craniofacial deformities.

PMID- 9658811
TI  - [Preoperative diagnosis of complex craniofacial syndromes].
AB  - The aim of this study was to evaluate stereolithography as a tool in craniofacial
      surgery. The indications were classified according to the usefulness of
      stereolithography for different craniofacial pathologies. Stereolithography
      models of 21 patients were built; in three cases two models were made. The age of
      the 7 male and 14 female patients was 17 years on average (range: 15 months-44
      years). First a helical volume CT scan of the anatomical region was performed.
      After transformation of the data set, the models were built by an SLA 250
      stereolithography apparatus (3D-Systems, Valencia, Calif., USA), steered by FORM
      IT/DCS-Software (University of Zurich, Switzerland). The stereolithography models
      were constructed by superposition of epoxy resin slices of 0.05 mm thickness,
      which were polymerized by a helium-cadmium laser. These models were classified
      according to the indication for stereolithography, the operation performed, the
      relevance for surgical planning and the usefulness for the fabrication of
      implants and protheses. In craniofacial syndromes, severe asymmetries of the
      viscerocranium, large skull defects and before surgical correction of
      hypertelorism these models provided important additional information for the
      surgeon. Before complex interventions in these fields the construction of a
      stereolithography model should be considered. In multiple fractures consolidated
      in dislocation, the models proved to be less useful.

PMID- 9658812
TI  - [Median craniofacial clefts. Therapy recommendations and late outcome].
AB  - Median craniofacial clefts are classified as median facian cleft deformities and
      are characterized by clefts of the nose involving the skull base. They can be
      accompanied by hypertelorism and/or encephaloceles. From a total of 22 of our
      patients with median deformities, three encephaloceles and two severe median
      nasal clefts with hypertelorism were considered in 2- to-8-year-olds. Two
      children with severe brain deformities died before the commencement of therapy.
      The remaining median deformities were corrected as soon as possible, whereby
      exclusively soft-tissue surgery was performed during the first year of life and
      in no case later than school admittance. Final corrections on the nasal skeleton
      were made after the age of 12. No growth disturbances of the middle face or jaw
      occurred subsequent to craniotomies and corrections of hypertelorism. Plate
      osteosynthesis has proven to be the most reliable method of stabilization; we
      removed the osteosynthetic material in all cases. The multiplicity of possible
      deformities requires that procedures be tailored to the individual case.

PMID- 9658813
TI  - Possibilities and developments of intraoperative image-guided surgery in
      craniofacial surgery.
AB  - The standardised operational techniques of fronto-orbital osteotomy and the
      various modifications used today make it possible to perform extensive surgery
      for the treatment of craniofacial malformations and advanced tumours in this
      region, while also allowing for a good extra- and intracranial view. Osteotomies
      and resections in areas of the skull base that are normally hard to reach have
      been considerably facilitated and the operational risk has been lowered. Our aim
      is to achieve a further reduction of the operational risks and of the post
      surgical morbidity rate through the use of techniques of computer-assisted
      surgery. Especially in the area of the complex anatomy of the skull base, use of
      the systems for the purpose of orientation and realisation of operational
      planning as well as for the control of how radical a tumour resection needs to
      be, have proved quite successful. Meanwhile, we have acquired experience in more
      than 100 clinical applications of mechanical and optoelectronical navigation
      systems. However, it is not possible to make changes to the presurgical data.
      Also, the flexibility of the system is still somewhat limited. By introducing a
      new referencing system, the flexibility and possible applications of navigation
      have been increased. The current possibilities and indications for the use of
      intraoperative navigation are discussed.

PMID- 9658814
TI  - [Modifications of fronto-orbital osteotomy as an approach to the anterior and
      middle skull base].
AB  - Various extracranial, intracranial and combined extra-intracranial approaches
      have been described for the surgical therapy of tumours of the anterior and
      medial cranial base. A combined extra-intracranial approach is indicated in cases
      in which the cranial base tumour spreads out intracranially and at the same time
      into the main nasal cavity, the paranasal space and/or the orbits. These tumours
      of the skull base can be surgically removed by two standardised modifications of
      the fronto-orbital osteotomy--the fronto-orbito-nasal and the fronto-orbito
      zygomatic osteotomy. The advantage of these surgical techniques in comparison
      with other methods is that they permit a good extracranial and intracranial view
      with only minimal brain trauma. Generally, additional transfacial incisions are
      unnecessary. The operative techniques are described and the results of 108 cases
      of tumours of the skull base shown.

PMID- 9658815
TI  - [Fronto-orbital corrections and development of the frontal sinus].
AB  - The development of frontal sinuses following bilateral fronto-orbital advancement
      is a topic of controversial discussion in the literature. In a retrospective
      study on 33 patients (15 girls and 18 boys) the development of the frontal sinus
      was examined radiologically. Only patients with a minimum age of 6 years and with
      at least 1 year of postoperative follow-up were included. The radiological
      reference for the frontal sinus development consisted of pneumatisation at or
      above the level of the supraorbital rims, as projected din postero-anterior
      cephalograms. According to these criteria a frontal sinus development was seen in
      72.7% of our patients. There was no statistically proven correlation between
      sinus development and the sex of the patient, age at surgery or the amount of
      advancement. With the exception of severe cases of Crouzon's disease we usually
      expect normal development of the frontal sinus following bilateral fronto-orbital
      correction.

PMID- 9658816
TI  - [Clinical application of osteoinductive implants in craniofacial surgery].
AB  - Autolyzed, antigen-extracted, allogeneic bone (AAA bone) is prepared from
      cortical bones of human organ donors. AAA bone possesses osteoinductive
      properties as it delivers BMPs from its bone matrix. Within a prospective study,
      37 cranial defects were reconstructed using AAA bone implants over a period of
      more than 7 years. The patients were followed-up at standardized intervals.
      Roentgenographic assessments and bone scintigraphies revealed osseous integration
      and remodelling of the AAA bone implants. In one quarter of the cases re-entry
      was performed 10 to 18 months after the cranioplasty (removal of osteosynthesis
      material, recurrence of tumor). All nine AAA bone reconstructions showed bleeding
      surfaces and bony integrations. A bone biopsy was taken from the center of one of
      these AAA bone implants and this showed new bone formation originating from the
      surface of the implant. In one case an AAA bone implant was lost due to
      infection. This is noteworthy as in approximately one third of the cases the bone
      implants were in direct contact with the frontal sinus. The clinical results
      clearly emphasize the therapeutical benefit of AAA bone for cranioplasties. Large
      AAA bone chips from human skull bones facilitate the reconstruction of the
      skull's convexity, especially when sterolithography-based operation planning is
      performed.

PMID- 9658817
TI  - [New hydroxylapatite cement for craniofacial surgery].
AB  - A new stoechiometric mixture of 27% dicalcium-phosphate (DCPA) and 73% tetra
      calcium-phosphate (TTCP) can be prepared with water intraoperatively to a paste
      that subsequently sets to a structurally stabile implant composed of
      hydroxyapatite (HA). Primary setting time is about 20 min; pH during setting
      ranges from 6.5 to 8.5. There is no relevant curing heat or expansion or
      contraction. Compressive strength is about 50 MPa, tensile strength about 8 MPa.
      Over a period of about 4 h in physiological milieu, the cement converts to
      hydroxyapatite. This product is no longer redissolvable in normal body fluid.
      This cement can be used for non-load-bearing applications especially in
      craniofacial bone surgery. Cranial defects due to tumour or trauma as well as
      deficits in the facial skeleton may be reconstructed using this new biomaterial.
      In nine of ten patients we used the hydroxyapatite cement successfully for
      reconstructions in the craniofacial area. Fluid control of the operation field
      and implant site is extremely important and sometimes difficult to achieve.
      Further applications could be all non-load-bearing augmentations such as filling
      of blocked paranasal sinuses, of dentoalveolar cysts and defects following dental
      apectomy or fixation of implanted hearing-aid electrodes. The perspectives for
      the hydroxyapatite cement include its application as a carrier for osteogenic
      protein preparations, especially because of its isothermic reaction and intrinsic
      osteoconductive characteristics.

PMID- 9658818
TI  - [Effect of early fronto-orbital advancement on growth of the frontal sinus and
      supraorbital area].
AB  - In 12 patients with craniosynostosis the influence of early fronto-orbital
      advancement on the growth of the frontal sinus and supraorbital region was
      examined. A follow-up examination at the age of 8 years showed a lack of
      pneumatisation of about 50%. However, there was no correlation between this score
      and the external contour. The frontal sinus has no dominant influence on the
      growth of the supraorbital region. In 9 out 12 of cases the very early operation
      time did not lead to disturbances of growth. A further follow-up examination of
      the patients after termination of growth at the age of 16 is planned.

PMID- 9658819
TI  - [Long-term outcome after corrective surgery of the neuro- and viscerocranium of
      patients with simple and syndrome-related premature craniosynostosis].
AB  - A retrospective and partly prospective study was conducted to analyse both
      clinically and cephalometrically the craniofacial growth pattern of patients with
      isolated and syndrome-related premature craniosynostosis after standardized
      fronto-orbital and midface advancement. The file data of 293 children with fronto
      orbital advancement were evaluated over an average period of 4.4 years. In
      addition, lateral teleradiographies of 117 patients from this group were
      cephalometrically analysed. Moreover, late results of 36 children and 8 adults
      with midface-advancement with an average follow-up period of 4.5 years were
      assessed. In contrast to linear craniectomy and so-called lateral canthal
      advancement, in only 8.2% of cases (24 out of 293 patients) were relapses
      requiring reoperation found in this study after fronto-orbital advancement. The
      evaluations indicate that with simple forms of craniosynostosis such as
      trigonocephaly and plagiocephaly predominantly very good or good growth can be
      observed. Cephalometric evaluation confirmed the limited potential of growth in
      the area of the anterior skull base and in the midface in the presence of
      syndrome-related faciocraniosynostoses. In such cases the cephalometrically
      confirmed maxillary hypoplasia, which increases in severity in the following
      order of syndromes 'Saethre-Chotzen-Crouzon-Apert-Pfeiffer', could be influenced
      only to a limited degree by fronto-orbital advancement. For this reason midface
      advancement is of secondary importance in children with very severe anomalies. In
      the present evaluation, a high rate of relapse of midfacial hypoplasia was to be
      found in children and adolescents after this operation in accordance with other
      references. Therefore, the indication for Le Fort III osteotomy in the growth
      period should be limited.

PMID- 9658820
TI  - [Cranial development after corrective skull surgery in craniosynostosis].
AB  - Craniofacial development may be potentially implicated after vault corrections in
      cases of craniosynostosis. The aim of this prospective study was the
      investigation of the surgical effect on calvaria growth, correlating the
      percentiles of a group of patients before and after craniosynostosis correction
      in relation to the normal percentiles of growth. The patient population consisted
      of 71 children; the postoperative follow-up time in 57 patients was more than 12
      months. Of the children followed up, 36 were male and 21 female. Thirty-six cases
      involved untreated non-syndromic craniosynostosis; the remaining 21 were syndrome
      cases. The patient ages ranged from 16 to 27 months. In 11 cases correction of an
      occipital craniosynostosis was carried out. The fronto-occipital circumference
      was registered in accordance with Prader's percentile table. The operative method
      included a fronto-parietal craniotomy, the temporary removal and shaping of the
      fronto-orbital band and a vault cranioplasty. During follow-up 13 patients
      treated with fronto-orbital advancement in cases of isolated craniosynostosis
      remained in the registered percentile curve. In 13 patients a change to a lower
      percentile curve was confirmed; 1 patient changed to a higher curve. In cases of
      syndromic craniosynostosis 10 patients remained in the post-operatively
      registered percentile curve; 8 patients changed to a lower and 1 patient to a
      higher percentile curve. No growth restriction of the reshaped calvaria after
      surgical correction of craniosynostosis was observed. No significant difference
      was found in the potential calvaria growth between syndromic and isolated
      craniosynostosis.

PMID- 9658821
TI  - [Midfacial callus distraction in a patient with Crouzon syndrome].
AB  - The treatment of syndromic hypoplasias of the midfacial complex, for example in
      Crouzon patients, is necessary at an early stage for functional and aesthetic
      reasons. If midfacial advancement is done by the traditional technique using bone
      grafts, it has often been seen that the normal occlusion originally achieved
      changes in an Angle class III, because the mandible grows regularly but not the
      midface. This problem could probably be solved if midfacial advancement is done
      by the gradual callus-distraction procedure. The local osteogenesis involves the
      possibility that there is normal growth of the midfacial complex even if the
      operation is performed in young children. Based on experience in mandibular bone
      lengthening, this new method was used in a 10-year-old Crouzon patient. As
      successful lengthening of the midface needs a stable device and a reliable base,
      a new midfacial distractor was designed using the principle of the halo-frame.
      With an advancement of about 22 mm the midfacial position was normalized and a
      regular overbite was achieved. In a case report the new technique is shown and
      the results are demonstrated and discussed. Despite this encouraging early result
      a long-term follow-up is not yet possible.

PMID- 9658822
TI  - [Interdisciplinary surgical therapy of tumors of the frontal skull base].
AB  - Most tumors of the anterior cranial base invade both the intra- and extracranial
      regions at the borderline of the cranial and facial skeleton. In surgical
      treatment of these lesions, combined craniofacial approaches are applied in
      accordance with the anatomical conditions. Surgery is performed by an
      interdisciplinary team of neurosurgeons and maxillofacial surgeons. To evaluate
      the effectiveness and the complications of this surgical concept, the data of 58
      patients treated over a 10-year period were collected. In these patients, 60
      operations were performed, including two operations for tumor recurrence. In 38
      cases, complete tumor removal was achieved. One patient died in the early
      postoperative period because of pulmonary embolism. Significant neurological
      deficits occurred in three patients. In most cases, postoperative complications
      and functional disability were both due to intradural invasion of the tumor.
      Nevertheless, in the majority of the cases radical tumor removal is achieved with
      acceptable morbidity when microsurgical techniques are applied for the resection
      of the intradural tumor. Both the meticulous repair of dural defects and the
      reconstruction of the anterior cranial base and orbit contribute distinctly to a
      reduction in the rate of postoperative complications and to acceptable cosmetic
      results.

PMID- 9658823
TI  - [Craniofacial techniques in traumatology].
AB  - The coronal incision is a versatile approach to midface or skull base fractures.
      It allows the open reduction of complex fracture sites and facilitates
      canthopexy, marginotomy or calvarian bone harvesting. By this method, primary
      treatment can be optimised and the rate of secondary corrective surgery can be
      reduced. All trauma patients who underwent this kind of intervention were re
      examined to check functional and aesthetic results. The complication rate was low
      and the advantages of these techniques are evident, so that it is suggested that
      the indication for this operative approach should be extended.

PMID- 9658824
TI  - [Obliteration of the frontal sinus with lyophilized cartilage in frontal
      fractures].
AB  - Obliteration of the frontal sinus is frequently necessary in the appropriate
      treatment of major craniofacial trauma of the upper third of the face. Successful
      frontal sinus obliteration requires (1) meticulous removal of the frontal sinus
      mucosa, (2) permanent occlusion of the nasofrontal duct and (3) obliteration of
      the denuded cavity. The current techniques include implantation of autologous
      fat, bone or muscle. These techniques are effective when the appropriate
      guidelines are respected, but the problems of donor site morbidity, which has
      been as high as 5%, recipient site morbidity due to the shrinkage of the free
      graft, and the increase in the operative time must be pointed out. The unique
      characteristics of lyophilized cartilage, i.e. the low resorption rate and
      tendency to undergo osseous substitution, justify its use for obliteration of the
      frontal sinus. The present study reviews 51 patients with obliteration of the
      frontal sinus due to craniofacial trauma. In none of the patients were there
      clinical or radiological signs of postoperative mucocele formation. Progressive
      ossification of the implanted cartilage was verified in most of the patient
      population.

PMID- 9658825
TI  - [Reconstruction of the frontobasal skull after tumor operations and trauma.
      Transplant selection and functional outcome].
AB  - Defects of the frontoorbital complex subsequent to extensive tumor surgery or
      severe trauma often result in aesthetic and functional disharmonies. The long
      term results of rehabilitation related to different materials and techniques are
      the subject of this study. From 1974 to 1996 altogether 127 patients with bony
      defects of the orbit and/or the skull base underwent surgery. All patients' data
      were documented prospectively from 1984 onwards. The results following
      reconstruction with autologous calvarian transplants in 52 patients were compared
      to those of a control group which received iliac bone or PMMA implants. Eighty
      one bony defects (64%) resulted from tumor resection; 37 patients (29%) suffered
      from the effects of trauma. In 67 cases (53%) reconstruction was performed
      primarily, in 51 cases (40%) secondarily. Free or pedicled soft-tissue
      transplants were necessary in order to separate the orbit and the neurocranium in
      26% of the defects. On the other hand, small, isolated defects of the orbital
      roof (7%) were left without any reconstructive procedure. Contrary to the iliac
      bone grafts, the calvarian transplants resisted secondary resorption.
      Postoperative infections appeared in two cases; loss of transplants was avoided
      entirely in the group of calvarian reconstructions in contrast to the alloplasts.
      The selection of a suitable donor site area and rigid fixation with microplates
      led to excellent esthetic results even in cases with large defects.

PMID- 9658826
TI  - [Standardized occipital advancement. A new method for therapy of lambda suture
      synostosis].
AB  - Lambdoid synostosis can manifest unilaterally, bilaterally or in combination with
      other craniosynostoses. Using the concept of fronto-orbital advancement we
      developed occipital advancement in order to correct unilateral or bilateral
      lambdoid synostosis. The process involves striped transversal osteotomy, removal,
      remodelling and advancement of the occipital region. It allows precise,
      reproducible and predictable positioning of the segments. Artificial sutures are
      created as a result of the osteotomy. The remodelling leads to a well
      proportioned skull shape and advancement to an increase in the intracranial
      volume. This article presents the operative method and the results of 14
      patients.

PMID- 9658827
TI  - [Occipital correction in scapho- and plagiocephaly].
AB  - The operation technique and the results after occipital correction in children
      with plagiocephaly and scaphocephaly are reported. The indication for the
      intervention is provided by aesthetic and functional considerations. The outcome
      is very good; the growth of the skull follows the same range of percentiles as
      preoperatively and normal mental development is seen.

PMID- 9658828
TI  - [Treatment of non-synostotic, pediatric skull deformities with dynamic head
      orthosis].
AB  - In all craniofacial deformities the differential diagnosis between synostotic and
      non-synostotic conditions must be made. While the first group is usually subject
      to intracranial surgical intervention, the treatment of non-synostotic
      deformities is the subject of controversial discussion. Often associated with
      premature birth, restrictive intrauterine environment or torticollis, these
      conditions; also defined as positional deformations, can lead to severe
      plagiocephalic head shapes. Dynamic orthotic cranioplasty is a conservative
      method of treating these deformities in early childhood by means of an
      individually fabricated orthotic head band. The principle is that dynamic
      pressure is applied to prominent parts while leaving space for growth in
      depressed areas. In accordance with this principle, various deformities can be
      addressed. Through clinical, anthropometric and radiographic evaluation it has
      been shown that dynamic orthotic cranioplasty can correct positional deformation
      of the cranial vault, skull base and upper face with no relapse following
      treatment. It must be emphasised that the method is simple, easy to handle and
      very effective when treatment starts within the first 6 months of life.
      Therefore, its potential should be recognised by paediatricians and craniofacial
      surgeons.

PMID- 9658829
TI  - [Tumor reduction of plexiform neurofibroma in the craniofacial and neck area].
AB  - Neurofibromatosis type 1 (NF1) is an autosomal dominant hereditary disease of
      high penetrance and variable expression. Epidemiologic data on craniofacial
      manifestations are still lacking. Up until now 74 patients with NF1 have been
      treated at the Department of Oral and Maxillofacial Surgery of the University of
      Hamburg. Forty-two patients presented periorbital and orbital neurofibromas
      varying in extension and in the severity of findings of the affected site.
      Surgical therapy is mainly based on tumour reduction, frequently combined with
      face-lifting. In our experience neurofibromas of the neck tend to be pseudo
      encapsulated, facilitating the preparation of the tumour. On the other hand,
      identification and preparation of diffuse infiltrating neurofibromas in the
      trigeminal nerve region are difficult and local recurrence must be expected.

PMID- 9658830
TI  - [MRI 3D imaging of the orbits in craniofacial abnormalities and injuries].
AB  - Craniofacial malformations and trauma often lead to changes in orbital soft
      tissues that require operative correction of both hard and soft tissues. CT scan
      and 3D reconstructions are optimal tools for the evaluation of the bony
      structures but there is no equivalent for the orbital soft tissues. The aim of
      this study was to establish a 3D-MRI technique that allows differentiated
      visualization of the different soft-tissue types of the orbit. A total of eight
      patients with different pathologic conditions of the orbit were examined. Five of
      these patients came for secondary correction after trauma and three showed a
      craniofacial malformation. 3D reconstruction was performed in volume-rendering
      technique after acquisition of 3 mm axial slices. It was shown that
      differentiated visualization of the orbital soft tissues is possible. Even though
      the thin bony structures have a weak signal and therefore the imaging is poor,
      the globe could be reconstructed reliably by different radiologists because of
      its circular delimitation from the bone. This technique provides additional
      support in the planning of orbital operations.

PMID- 9658831
TI  - [Results of surgical therapy of orbital abnormalities].
AB  - Dystopies of the bony orbit are caused mainly by craniosynostosis, facial clefts
      and encephaloceles. This article presents the results of the surgical correction
      of orbital hypertelorism in 24 patients. Using this operation technique, the bony
      interorbital distance was decreased from an average of 47.6 mm to 22.8 mm.
      However, the distance between the soft tissues was not reduced by the same amount
      as the distance between the bony orbits. The intercanthal distance decreased from
      an average of 58.5 mm to 44.5 mm, whereby an additional refixation of the medial
      palpebral ligament resulted in a reduction of the intercanthal distance to 40.8
      mm. A strabismus divergens was seen preoperatively in 18 patients,
      postoperatively only in 8 patients. Four of the latter had to undergo operative
      correction of the diplopia. We conclude that the operative technique is not
      reserved only for complex cases of hypertelorism because it shows satisfactory
      functional and aesthetic results with a low complication rate.

PMID- 9658832
TI  - [Using individually designed ceramic implants for secondary reconstruction of the
      bony orbit].
AB  - The use of autogenous transplants and the application of intraoperatively
      customised alloplastic materials show, in cases of secondary orbital
      reconstruction, a higher postoperative morbidity caused by additional approaches
      to the transplant donor site. On the other hand, thorough surgical exploration
      and fitting of the transplants or alloplastic materials greatly prolongs
      operating times. For these reason we designed ceramic implants (Bioverit) on the
      basis of stereolithography models and prefabricated them using a commercially
      available dental copy milling unit (Celay). In five cases up until now seven
      customised implants have been inserted for reconstruction of the lamina
      papyracea, zygomatic complex and infraorbital floor and rim. Encouraged by the
      good postoperative aesthetic and functional results, with significantly reduced
      operating times and morbidity in all cases, we will continue to take this
      technique into account for reconstruction after complex orbital fractures.

PMID- 9658833
TI  - [Orbital decompression in treatment of endocrine orbitopathy].
AB  - Graves' ophthalmopathy (Graves' disease) is a grave, rare immunological
      inflammatory reaction of the postorbital connective, adipose and ocular muscle
      tissue. Graves' disease occurs only within the scope of immunothyropathies and
      constitutes the most frequently encountered extrathyroidal manifestation. Typical
      symptoms are a result of the volume increase of the postbulbar connective and
      adipose tissue and of the interstitial swelling of the ocular muscles.
      Clinically, we find a spectrum of increasingly grave changes in the orbita, such
      as infiltration of the eyelid and connective tissue, exophthalmos, swelling of
      the muscles, damage to the cornea and involvement of the optic nerve with loss of
      vision. Regarding functional impairment of the optic nerve (optic nerve
      compression), orbita decompression represents an operative ultima ratio. Between
      January 1992 and April 1997, 11 patients (22 orbitae) from a group of more than
      600 patients with Graves' disease with vision involvement were treated
      surgically. All treatment data were documented prospectively. Surgical
      intervention was performed only in cases where a progressive loss of vision
      existed in spite of retrobulbar irradiation and high-dose glucocorticoid therapy.
      Surgical therapy consisted of decompression of the medial, inferior and lateral
      orbital wall and of the orbital contents via combined bi-coronary and anterior
      access. The long-term results demonstrated improved vision conditions with 17 of
      the 22 eyes operated on. Parameters such as vision, exophthalmos, VEP, motility,
      double vision and field of vision were documented pre- and post-operatively. The
      prediction of post-operative deviations of the bulb axis was limited, and these
      were rectified through secondary displacements of the ocular muscle. No
      complications worth mentioning were encountered. In extreme events of therapy
      resistant Graves' ophthalmopathies with progressive loss of vision, the three
      wall decompression method has proved to be the correct one.

PMID- 9658834
TI  - [Interdisciplinary diagnosis and therapy of traumatic optic nerve damage].
AB  - Traumatic optic nerve lesions (TONL) still pose a large clinical problem
      concerning early detection and treatment. Neuro-ophthalmology provides reliable
      tests to detect afferent lesions but these methods are limited to just 30% of the
      severely injured patients. Especially in the patient with multiple injuries,
      optic nerve injuries are hardly predictable. In the latter group we established
      well-known neurophysiological methods for early detection of afferent disorders
      of the visual pathway, i.e. flash-VEP ERG. Apart from these diagnostic problems
      of TONL, controversy still surrounds the appropriate treatment of TONL--whether
      conservative or surgical or even combined treatment should be advocated. Our aim
      was to establish a reliable diagnostic schedule, based on the combination of
      neuro-ophthalmological, spiral-CT and clinical findings, and a treatment plan, so
      that in any patient there is a distinct guideline as to whether there is a need
      for early treatment of the peripheral visual pathway or not. In 52 patients who
      were assessed by the above-mentioned schedule, we could detect any of the 20
      afferent disorders of the peripheral visual pathway. Although it is difficult to
      prove therapeutic effects on the injured optic nerve, immediate combined
      conservative treatment plus optic nerve decompression helped in three patients,
      who reported unilaterally no light-perception at admission, to regain at least
      partial recovery of afferent function of the visual pathway. Most of the trauma
      units still handle the problem of optic nerve trauma with a 'wait and see'
      policy. This is not regarded as an up-to-date option, since there are
      alternatives, and these will be outlined.

PMID- 9658835
TI  - [Foreign body removal in orbits and frontal cranial base].
AB  - Owing to their rare incidence, foreign body injuries in the region of the orbit,
      skull base and skull have up to now mostly been treated in the literature by
      means of case reports. Here we present our experience and treatment regimen for
      ten patients we have treated during the last 3 years. In seven cases the foreign
      body was located in the orbit alone, whereas in three others the orbit and the
      frontal base were equally involved. Except for one case, the foreign material
      could be removed completely. Three patients suffered from partial or complete
      loss of vision and one patient developed a psychosyndrome during the follow-up
      period, but no late effects were registered in the remaining six cases. Before
      removing the foreign body and carefully reconstructing the accident, however, we
      strongly recommend the documentation of possible functional deficits, preferably
      by means of photography. CT is the method of choice for localising the foreign
      body, except for the depiction of wood particles. Here, sonography and MR should
      be performed. As the therapeutic approach, the cooperation of an
      interdisciplinary team of ophthalmogists, neuro- and maxillofacial surgeons seems
      mandatory. To avoid inflammation, the immediate removal of the foreign material
      is recommended in cases with considerable intracranial lesions: post-operative
      neurologic and intensive care monitoring should be provided. Treatment is
      completed by high-dose antibiotics, using CSF-soluble substances and, if
      necessary, anti-convulsives.

PMID- 9658836
TI  - [Experimental reconstruction of the sheep orbit with biodegradable implants].
AB  - In a complex animal model in sheep, polydioxanone (PDS) and polylactic membranes
      were used for the reconstruction of large orbital-wall defects. In a long-term
      experiment over 1 year, polylactic implants alone showed the best performance as
      compared with combinations involving autogenous bone grafts and titanium
      miniplate fixation. As soon as these polylactic implants are approved for human
      surgery, they will be used to solve the still challenging problem of anatomical
      reconstruction of large comminuted fractures of more than one orbital wall.

PMID- 9658837
TI  - [New techniques in maxillofacial surgery: local injection treatment with
      botulinum toxin A].
AB  - Intramuscular injections of botulinum neurotoxin type A cause reversible
      chemodenervation and subsequent paralysis by blocking the presynaptic release of
      acetylcholine. Botulinum toxin type A has emerged as the most effective form of
      symptomatic treatment for abnormabilities in muscle movement (blepharospasm,
      hemifacial spasm, torticollis) and has been approved for use in these conditions.
      First results in the treatment of patients suffering from oromandibular dystonia,
      myogenic craniomandibular dysfunction and recurrent dislocation of the
      temporomandibular joint are presented. In most cases, therapeutic effects
      occurred within 1-6 days post-injection. Muscular hyperfunction was reliably
      reduced and involuntary activity patterns gradually ceased. No severe side
      effects of the local injections were noted.

PMID- 9658838
TI  - [Botulinum toxin treatment of neurogenic dislocation of the temporomandibular
      joint].
AB  - Botulinum toxin leads to paresis of the skeletal muscle lasting 2-4 months via an
      inhibition of acetylcholine release at the neuromuscular junction. Since 1995,
      botulinum toxin injections have been used in the treatment of recurrent
      dislocation of the temporomandibular joint (TMJ). The chemical denervation of the
      external pterygoid muscle restricts the angle of mouth opening, thus helping to
      prevent dislocation. TMJ dislocations that occur as a result of increased tone in
      the protracted masticatory muscles were recently defined as neurogenic
      dislocations of the TMJ. We conducted a clinical study to investigate the
      efficacy of botulinum toxin injections into the external pterygoid muscle in five
      patients with recurrent neurogenic dislocations of the TMJ. In the 3 months prior
      to the first treatment, the patients had suffered a total of 19 dislocations. In
      the 3-month period following the initial treatment, only one woman experienced a
      dislocation. We performed the treatment a total of 25 times. Five dislocations
      occurred during the 6- to 36-month observation period. In the meantime, two
      patients remain recurrence-free 1 year after receiving treatment. All the
      patients had a restricted ability to open their mouths as a side effect of the
      weakening of the external pterygoid muscle that was completely reversible over
      the course of 3-4 months. All other side effects were equally well-tolerated by
      the patients and fully reversible after 3 weeks at the most. In the two patients
      who remain recurrence-free without any further treatment, the increased tone of
      the muscles serving the jaw normalised spontaneously over the course of the
      underlying neurological disease. Our results show that, in the treatment of
      recurrent neurogenic dislocations of the TMJ, botulinum toxin injections
      represent a therapeutic alternative that has few side effects.

PMID- 9658840
TI  - [A new device for reproducible computerized tomography in improved diagnosis of
      surgical maxillofacial conditions].
AB  - The aim of this study was the evaluation of a newly developed radiotranslucent
      headholder (craniostat) in order to improve diagnosis of maxillofacial pathology.
      In this prospective study, 103 patients with maxillofacial pathology were
      examined preoperatively with a Philips SR 7000 computed tomograph using this
      craniostat. The apparatus was applied fixing the patient's head at three points
      (meatus acusticus externus on both sides and the glabella). The control group
      consisted of 106 patients with similar pathology who were examined by computed
      tomography without a headholder. The application of the craniostat resulted in
      the following advantageous findings: (1) reproducible CT scans, therefore very
      precise assessment of the course of a disease; (2) fewer motion artifacts; and
      (3) symmetrical posture of the patient's head. This headholder is helpful in
      improving maxillofacial diagnosis by computed tomography if a symmetrical,
      reproducible posture of the patient's head is to be achieved and motion artifacts
      could otherwise make the interpretation of the resulting images much more
      difficult.

PMID- 9658839
TI  - [3-D imaging of the facial surface by topometry using projected white light
      strips].
AB  - Three-dimensional registration of the facial surface by methods which are
      currently in use is difficult because of the long measuring times required by
      point-based imaging systems. Artifacts caused by movement appear, e.g., blinking.
      Also the production of a facial plaster-cast model for measuring is not an
      adequate solution. In order to acquire data of the facial surface in a contact
      free manner, a system is needed that has short measuring times, is able to record
      data of complex surfaces and at the same time does no harm to the open eyes. The
      method described here represents a new development of an industrial high tech
      CAD/CAM system. Unlike customary point-based imaging systems, the stripe
      projection method works using entire planes. Structured light is aimed at the
      surface to be measured, recorded by videocamera and calculated by triangulation;
      then the different views are combined by computer. The system has an optic sensor
      that can record approximately 500,000 measuring points within seconds (ca. 1.7s).
      Test persons' faces and plaster-cast models of them (n = 15) were measured
      comparatively and serially (n = 5) to test the validity and reliability of the
      method for maxillofacial procedures. These investigations show that this method
      is appropriate for recording three-dimensional soft-tissue profiles. First
      studies on patients before and after dysgnathia operations were undertaken. A
      prospective long-term study for collecting data on pre- and postoperative
      dysgnathia patients has been begun. Initially, it will record the changes in
      facial soft tissue on the basis of skeletal displacement. Later, predictions
      about the soft-tissue changes subsequent to dysgnathia surgery can be worked out
      on the basis of stored data matched with three-dimensional bone data.

PMID- 9658841
TI  - [Results of measurement of pre- and postoperative milling models of orthodontic
      surgical treatment of dysgnathia patients].
AB  - PURPOSE: Three-dimensional realisation of CT by models produced by a milling
      machine and stereolithography has become a useful procedure for the diagnosis of
      craniomaxillofacial disharmonies. We used three-dimensional milling models to
      verify the results of operations involving sagittal splitting of the mandible.
      MATERIAL AND METHODS: Fifteen models from patients with mandibular prognathism
      and 31 models from patients with mandibular retrognathism, made preoperatively
      and 6 weeks postoperatively, were examined for three-dimensional changes of the
      osseous anatomical structures. RESULTS: The mandibular corpus had been shifted
      between 1 and 3 mm forward in the group of patients with mandibular retrognathism
      and by the same distance backward in the first group. In the group with ventral
      shifting, the intercondylar distance increased by 2.9 mm, while it decreased by
      1.9 mm in patients with the mandibular backshift operation. Furthermore, the
      distance between the muscular processes increased by 6.6 mm in the first group
      and decreased by 1.6 mm in the second. The Bonewill angle decreased by 1.6
      degrees in patients after ventral shifting and increased by 1.7 degrees in the
      dorsally shifted group. Contrary changes in the left and right gonion angle were
      seen: if the right decreased, the left increased. The same situation was found in
      both groups. CONCLUSION: We noted remarkable changes in the condylar position and
      anatomy after sagittal splitting of the mandible.

PMID- 9658842
TI  - [Intraoperative precision of mechanical, electromagnetic, infrared and laser
      guided navigation systems in computer-assisted surgery].
AB  - Intraoperative precision in computer-assisted surgery depends on the
      characteristics of a navigation system, the precision of correlation between
      object and data set, the position, number and fixation of landmarks, and the
      parameters of the data set. The characteristics of a navigation system, in
      particular the immanent precision, can be detected by the use of the geometric
      model and navigation analyzer developed at the University of Regensburg with the
      support of Carl Zeiss, Germany. The precision of five navigation systems of
      different types and technology was measured: Viewing Wand (ISG, mechanical
      system), the SMN microscope (Carl Zeiss, infrared system with laser autofocus),
      the MKM system (Carl Zeiss, robot platform with laser autofocus) and the STP
      pointer (Leibinger, infrared system). The immanent precision of these systems
      ranges from 0.1 to 2.0 mm. An electromagnetic system (3-Space Digitizer,
      Polhemus) was compared; this produces serious spherical deviations of 10.0 to
      20.0 mm in the presence of metal, surgical and rotating instruments, and
      circuits. The application of these different systems for craniomaxillofacial
      surgery is discussed.

PMID- 9658843
TI  - [Biological activity of E. coli expressed BMP-4].
AB  - BMP-4 is physiologically present in low concentrations in human bone matrix. So
      far the protein has only been produced in small quantities by expression in
      mammalian cell cultures. In this study we investigated the biological activity of
      E. coli-expressed BMP-4. In vitro neonatal rat muscle tissue was incubated
      together with BMP-4 during 4 h, followed by an incubation period of 14 days on
      cellulose acetate membranes in BMP-free medium. The addition of 0.4 microgram BMP
      4 induced cartilage formation in 1/8 samples while 4 micrograms BMP-4 showed
      chondroneogenesis in 2/10 samples. When the BMP-4 concentration was increased to
      40 micrograms, new cartilage formation was seen in 5/7 samples. In vivo BMP-4 was
      implanted intramuscularly for 3 weeks in ICR mice. Amounts of 10 micrograms rhBMP
      4 and more (up to 100 micrograms) constantly induced heterotopic ossicle
      formation. BMP-4 was also combined with a collagen carrier and implanted for 2
      and 4 weeks in the abdominal muscle of SD rats. While 0.4 microgram BMP-4 showed
      no bone or cartilage formation, the amount of 40 micrograms BMP-4 showed new
      heterotopic cartilage formation, followed by endochondral ossification in almost
      all samples. The results prove that E. coli-expressed BMP-4 possesses the same
      inductive properties as mammalian-cell-expressed BMP-4.

PMID- 9658844
TI  - Preoperative assessment of airway patency in the planning of corrective cleft
      nose surgery.
AB  - OBJECTIVE: To investigate acoustic assessment of complex structural anomalies in
      cleft lip and palate associated nasal deformities and its impact on the planning
      of corrective rhinosurgery. PATIENTS: Twenty-three consecutive patients with
      unilateral CL(P) during routine consultations, three of them prior to corrective
      surgery. INTERVENTION: Acoustic measurements of the nasal airway crosssectional
      area were obtained for both nasal cavities. The size of isthmus area and isthmus
      location as well as the nasal volume and decongestion capacity in various regions
      of interest were determined. RESULTS: Obstructions in the area of the nasal valve
      (< 0.4 cm2) were detected in 85% of the patients on the cleft side, but only 15%
      on the contralateral side. Severe mucosal hypertrophy was a common finding on the
      cleft side with a significantly higher capacity of decongestion, especially in
      the posterior region of the nasal cavity (P < 0.02). A second stenosis located
      behind the physiological isthmus was found in 16 patients. CONCLUSION: Acoustic
      rhinometry is a noninvasive, objective method. It measures the degree and the
      exact location of airway obstructions. Apart from the equipment, the only
      prerequisite is a cooperative patient. The measurement has direct therapeutic
      consequences. If the exact cause and location of airway stenosis are known, it is
      easier to adapt the corrective surgical procedures to suit the individual
      patient. The decision in favour of additional therapeutic measures can be made on
      a more rational basis to prevent residual airway problems postoperatively.
      Preoperative acoustic rhinometry offers valuable information concerning the
      severity and location of nasal airway obstructions and thus proves to be a
      helpful tool in the planning of corrective operative measures.

PMID- 9658845
TI  - Objective evaluation of velopharyngeal function by acoustic reflection
      measurements.
AB  - OBJECTIVE: To investigate whether acoustic pharyngometry is capable of
      discriminating velopharyngeal mobility in cleft and non-cleft subjects by
      determination of epipharyngeal volume changes with active muscle function.
      DESIGN: Case control study, consecutive sample. SETTING: Cleft palate
      rehabilitation centre. PATIENTS: Thirty-three consecutive cleft palate patients,
      among them 10 following pharyngeal flap surgery and 32 controls without
      velopharyngeal pathology. INTERVENTION: Transnasal acoustic measurements of
      airway cross-sectional area in the state of relaxed and tensed pharyngeal
      muscles. Determination of epipharyngeal volume changes by integrating the
      difference of the airway profile from the choane for a distance of 5 cm (EV0-5).
      Measurements of defined changes in the epipharynx served as reference. RESULTS:
      Acoustic pharyngometry is capable of discriminating (P < 0.05: U test, Mann
      Whitney) the volume effect of velopharyngeal mobility in CP patients (6.5 cm3)
      from the control group (8.0 cm3). A 'pharyngeal flap type' and a 'non-pharyngeal
      flap type' of restriction was observed. The individual effect of
      velopharyngoplasty on pharyngeal mobility can thus be determined. CONCLUSION:
      Acoustic pharyngometry is a non-invasive, quantitative investigation technique
      which seems well suited for the evaluation of velopharyngeal mobility. We expect
      it to be a helpful tool in objectively monitoring the effect of therapeutic
      intervention on velopharyngeal mobility, and it may provide a better
      understanding of the pattern of movement in CP patients.

PMID- 9658846
TI  - New perspectives in head and neck sonography by signal-enhanced color Doppler
      sonography.
AB  - Ultrasound contrast agent is used in color Doppler flow imaging for signal
      enhancement in perfused vessels. We present our experience with its use in the
      head and neck area and the results obtained. Up until now, 30 patients with
      carcinomas of the oral cavity or the maxillary sinus, tumors of the mandible and
      metastatic or inflammatory lymph nodes have been examined. Conventional B-scan
      sonography was supplemented by non-contrast color Doppler flow imaging. Depending
      on the indication, 2.5 g Levovist in bolus or 4 g fractionated was injected
      intravenously in a concentration of 300 or 400 mg/ml. The administration of the
      contrast agent was tolerated by all patients without any side effects and in all
      cases led to a remarkable enhancement of the Doppler signals. About 15 to 30 s
      after injection, an enhancement in perfused vessels was detected. The fractioned
      injection of 4 g led to a lengthening of signal enhancement up to more than 10
      min and to the possibility of examining more parts with a single application of
      contrast agent. In 64% of the lymph nodes, vessels could only be identified with
      the administration of Levovist. The general vessel topography could be better
      evaluated in 83% of the cases. The lymph-node-supplying vessels were identified
      in 8 of 11 patients after the injection of contrast media. Additional
      information, which was gained in 17 patients, increased the certainty of
      diagnosis or of the therapeutic concept. In three cases, the examinations with
      the signal enhancer resulted in a change in therapy. By applying signal enhancer
      in color Doppler sonography the fields of examination in the head and neck areas
      can be expanded.

PMID- 9658847
TI  - [Endoscope-assisted fixation of condylar fractures of the mandible].
AB  - The reduction and plate osteosynthesis of condylar fractures often require a wide
      extraoral approach with the risk of facial nerve palsy. The endoscopic technique
      is an alternative. Seven condylar fractures were operated on under endoscopic
      control. In three patients a newly developed device for endoscopically controlled
      plate application was clinically tested for osteosynthesis. In two cases fracture
      healing was achieved. In the third case the plate had to be removed early due to
      insufficient screw fixation. The new device and the application technique are
      described in detail. This technique may be helpful in further minimizing trauma
      surgery.

PMID- 9658848
TI  - [Status of the temporomandibular joint after orthodontic-surgical interventions
      with and without concomitant orthodontic treatment].
AB  - PURPOSE: This study was conducted to control improvement in the high preoperative
      prevalence of TMJ symptoms in patients treated by long-term orthodontic therapy
      for class II malocclusion. PATIENTS AND METHODS: A total of 57 patients were
      examined at least 8 years after surgery, 37 having received orthodontic treatment
      and orthognathic surgery and 20 surgery but without orthodontic treatment.
      Myofunctional, disk and condylar symptoms were recorded according to the Krough
      Poulsen scheme. RESULTS: Both groups showed a normal maximal interincisal
      distance. The deviation during the opening movement was mainly sigmoidal in the
      group with orthodontic treatment and terminal in the other group. Muscular pain
      predominated in the group without orthodontic treatment. Clicking sounds of the
      TMJ were registered in 70% of both groups. Occlusal interference and a higher
      interocclusal distance when speaking were found more often in patients without
      orthodontic treatment. Preoperatively, clicking and crepitation sounds had been
      recorded in 60% of both patients groups. CONCLUSION: In conclusion, a high
      postoperative prevalence of TMJ dysfunction symptoms was found in patients with
      class II malocclusion 8-10 years after orthognathic surgery with or without
      orthodontic treatment. Both groups often exhibited TMJ clicking and crepitation
      sounds, whereas the patients that had not received orthodontic treatment had a
      higher prevalence of occlusal interference and muscular pain.

PMID- 9658849
TI  - [Function and morphology of the temporomandibular joint after mandibular
      translocation osteotomies with and without positioning plates].
AB  - Positioning devices are commonly used to avoid the malpositioning of the proximal
      segments in bilateral, sagittal split osteotomies and to make sure the
      preoperative fossa condyle relation is reproduced. The aim of our prospective
      study, with random selection of 24 patients, was to compare the morphological and
      functional outcome of the TMJs. The proximal segments in half of the patients had
      been positioned using devices, in the other half without devices. The segments
      were fixed by transoral bicortical miniscrew fixation. The evaluation of function
      is based on pre- and postoperative clinical and electronic axiographic
      investigations. To study the TMJ morphology, we performed MRI and X-ray
      investigations preoperatively and 6 months postoperatively. Preoperatively, 12
      patients showed slight dysfunction, six patients moderate, and six patients
      severe dysfunction. Postoperatively, no patient was symptomless. Slight
      dysfunction was presented in 15 cases, moderate dysfunction in five and severe
      dysfunction in four cases. Evaluating the axiographic investigations
      preoperatively, 22 patients showed no mobility disturbances of the TMJ. Two
      patients showed severe mobility disturbances. Postoperatively, a significant
      increase in TMJ mobility disturbances could be seen. The MRI investigations of
      both groups showed both worsening and improvement in the disk positions. No
      significant differences could be determined between the two groups, however.
      Regarding the X-ray investigation, three patients from the group with positioning
      devices showed dislocated condyles; in the group without positioning devices four
      cases of condyle dislocation were seen. All dislocations were transversal except
      for one case in the group without positioning devices. Positioning devices do not
      seem to improve the functional and morphological outcome of the TMJ after BSSO.

PMID- 9658850
TI  - The changing face of mental health managed care.

PMID- 9658851
TI  - The managed care context: emerging practices.

PMID- 9658852
TI  - Behavioral health: a view from the industry.

PMID- 9658853
TI  - Utilization review and the treatment of mental illness: emerging norms and
      variabilities.

PMID- 9658854
TI  - The economics of behavioral health carve-outs.

PMID- 9658855
TI  - Medicaid managed care for special need populations: behavioral health as "tracer
      condition".

PMID- 9658856
TI  - Quality assurance in behavioral health.

PMID- 9658857
TI  - Consumer and family views of managed care.

PMID- 9658858
TI  - Behavioral health contracting.

PMID- 9658859
TI  - The effect of the Utah Prepaid Mental Health Plan on structure, process, and
      outcomes of care.
AB  - Capitation reduced Medicaid costs but had limited effects on most measures of
      process and outcome. Clients under capitation with the poorest mental health at
      baseline performed more poorly over time on some measures.

PMID- 9658860
TI  - Managed mental health experience in Colorado.

PMID- 9658861
TI  - Managed mental health experience in Massachusetts.

PMID- 9658862
TI  - The future of behavioral health.

PMID- 9658863
TI  - [Molecular genetics of gliomas].
AB  - Gliomas represent the majority of primary central nervous system tumors in
      adults. The moderate overall impact of conventional therapeutic regimens on these
      inherently aggressive neoplasms raises the need for a direct intervention in the
      biology of neoplastic change. In the last decade important achievements in the
      molecular genetic basis of deregulated cell-cycle have been brought about, the
      neuro-oncologic implications of which are reviewed here. Loss of equilibrium
      between promoting factors and negative control of mitosis emergeus as a general
      principle, with gene amplification-overexpression operating in the former group,
      while deletions, loss of function-type mutations and post-transcriptional events
      prevail at the opposite pole. Damage to regulatory mechanisms will result, as a
      major consequence, in transgression of one or more of the so-called restriction
      points of the cell-cycle. Lesions of the genome are further ramified by
      supracellular processes involving autocrine and paracrine growth-stimulating
      loops. Malignant progression of gliomas, therefore, can be envisaged as a
      cumulative sequence of genetic alterations and interactions of tumor cells with
      their microenvironment.

PMID- 9658864
TI  - [Hemorheologic parameters in coronary artery disease].
AB  - Hemorheological parameters were proved to be primary risk factors in ischemic
      heart disease (IHD) by several studies. In the present study the relation of
      these parameters to the severity of coronary artery disease (CAD) was examined.
      The data of 109 patients (mean age: 55 +/- 9 yrs) undergoing coronary angiography
      and 59 healthy controls (mean age: 35 +/- 10 yrs) were analyzed. Hemorheological
      parameters [hematocrit, fibrinogen level, plasma viscosity (PV) and whole blood
      viscosity (WBV)] were measured and circulatory index (CRI) was calculated.
      Patients were classified into three groups according to their coronary vessel
      state based on the coronary angiogram: Group 1 (n = 19, mean age: 53 +/- 8 yrs)
      without significant CAD, Group 2 (n = 19, mean age: 51 +/- 11 yrs) with single
      vessel disease, Group 3 (n = 71, mean age: 57 +/- 8 yrs) with multivessel
      disease. All the measured hemorheological parameters of IHD patients were
      significantly higher than those of controls. Fibrinogen and PV was significantly
      elevated in Group 2 and 3 comparing to Group 1 (p < 0.05 and 0.01). Hematocrit
      and WBV was significantly increased in Group 3 comparing to Group 1 and 2 (p <
      0.05). CRI was significantly decreased in IHD patients, and it was also lower in
      Group 3 than in Group 2 (p < 0.05). These results indicate that hemorheological
      parameters may play a role in the pathogenesis and development of CAD.

PMID- 9658865
TI  - [HIV protease inhibitors (new possibilities in the treatment of HIV infection and
      AIDS)].
AB  - In HIV/AIDS illness the reverse transcriptase and protease enzymes of human
      immunodeficiency virus (HIV) are currently the agents of antiretroviral therapy.
      Nucleoside analogues were the first group of drugs which exerted antiviral
      activity in humans. More recently protease inhibitors have provided new
      approaches in the treatment of HIV-infection and AIDS. Impressive clinical
      results have been obtained with combined therapies of three antiretroviral drugs,
      including one protease inhibitor. It is worth to mention that apart from the
      above, many new compounds are under development, including the vaccine against
      HIV.

PMID- 9658866
TI  - [Clinical experience with enzymes (collagenase, protease) in the treatment of
      skin lesions caused by CO2-laser surgery].
AB  - The authors applied collagenase and protease in lipofil solution for the
      treatment of skin lesions caused by CO2 laser interventions. 354 surgical
      interventions were performed on 91 patients (43 verruca vulgaris, 32 naevus
      intradermalis, 16 keratosis). The laser methods were excision or/and vaporisation
      of the lesion. The authors created methodological groups and all of the patients
      had a control laser wounds without enzymatic treatment. The patients were
      controlled periodically from the 1st to the 56th postoperative day. The first
      experience shows that, the use of enzymatic treatment is advantageous for the
      laser wounds healing. The colour, scar formation and other aspects proved to be
      better after the enzymatic treatment. The optimal method was the use of the cream
      for 2-4 postoperative days on very thin layer, without bandage. The result seemed
      to be better compared with the enzymatically untreated cases.

PMID- 9658867
TI  - [Biometry: data scales].
AB  - In this paper the author shows the basic concepts of the different data scales,
      which are important from statistical investigations points of view. He summarizes
      the characteristics of each scale and presents their sample data.

PMID- 9658868
TI  - [In memory of the 175th anniversary of the birth of Ignac Hirschler].

PMID- 9658869
TI  - [Nomination of Jozsef Torok in Debrecen].

PMID- 9658870
TI  - [Bacterial vaginosis].
AB  - Bacterial vaginosis being the most frequent vaginal infection is the leading
      cause of genital fluor. The author reviews the latest developments regarding the
      etiology, diagnostics and therapy of disease. Per os metronidazol and
      intravaginal clindamycin play the main role in treatment. The most often
      occurring complications of bacterial vaginosis are premature rupture of membrane
      and premature labour, postpartum endometritis, pelvic inflammatory disease and
      gynecological postoperative infections.

PMID- 9658871
TI  - [The effect of theophylline preparations on morphine-induced spasm of Oddi's
      sphincter in man].
AB  - In this paper a short overview is given about pathophysiology of Oddi's sphincter
      function and diagnosis as well as pharmacological therapy of the hypertonic
      dyskinesia. According to the pharmacological background of muscle relaxation in
      other organs, theophyllin preparations: aminophyllin and retard theophyllin were
      used to inhibit spasm of Oddi's sphincter provoked by morphine in 9 patients with
      hypertonic dyskinesia of biliary and/or pancreatic outlet. The enzyme elevations
      (SGOT and/or amylase) and pain response to morphine significantly diminished in
      all but one patient during the evocative tests and the effect seemed to be dose
      dependent until about 500 mg of theophyllin. The long acting theophyllin may be
      useful in hypertonic Oddi's sphincter dyskinesia mainly in combination with
      nitrates to prevent nitrate tolerance and intolerance and for treatment of
      "idiopathic" pancreatitis as well as "postcholecystectomy" syndrome. It might
      prevent papillary stenosis and adenomyosis which seem to be precancerous states
      of the papillary tumors.

PMID- 9658872
TI  - [Anesthesia for heart transplantation].
AB  - Heart transplantation, as a therapeutic possibility, has been available since
      1992 in Hungary. The authors present the anaesthetic aspects and clinical
      experiences of this worldwide used therapeutic method. The specialties of the
      narcosis, the importance of the aseptic techniques, and the treatment of the
      denervated heart are emphasised.

PMID- 9658873
TI  - [Computer tomography and interventional radiologic methods in the diagnosis of
      acute pancreatitis].
AB  - The authors supervised the case record of 51 patients admitted between 1994
      January and 1996 March suffering from acute pancreatitis. Diagnosis was made upon
      clinical signs, laboratory findings, abdominal ultrasound and CT examinations. In
      total 121 CT examinations were made mostly by using contrast material. Patients
      were classified with the help of Balthazar's grade. The authors emphasize that CT
      currently is the most accurate single imaging modality for diagnosis, staging the
      severity of the inflammatory process, and detecting complications of acute
      pancreatitis. They suggest that the first CT examination should be done within 3
      days from the onset of the illness. In cases falling under group "C", "D" or "E"
      of Balthazar's grade, the CT examination should at least be repeated within 10
      days. With 6 patients in septic state the bacteriological findings gained by fine
      needle aspiration was of great value for the further treatment.

PMID- 9658874
TI  - [Quinidine-induced syncope simulating transient cerebral ischemic attack].
AB  - A case of quinidine-induced syncope with prevailing neurological symptoms is
      reported in which the transient right-sided hemiparesis and fluctuating soporific
      state was induced by recurrent torsades de pointes ventricular tachycardias. In
      connection with this case, attention is paid to the difficulties of differential
      diagnosis and to the consideration of cardiac and metabolic disorders mimicking
      TIA or ischaemic stroke.

PMID- 9658875
TI  - [Treatment of mycobacterial lung diseases in patients without HIV infection].

PMID- 9658876
TI  - [Evaluation of diagnostic and therapeutic management in patients with
      bacteriologically negative pulmonary tuberculosis].
AB  - The study aimed at assessing the frequency and type of errors in the diagnosis
      and management of newly registered bacteriologically negative cases of pulmonary
      tuberculosis. Random sample of 560 out of 7272 such patients registered in 1993
      was subject of detailed analysis of all available medical documentation. The
      analysis was performed by an independent team of three specialists:
      pulmonologist, radiologist and epidemiologist. The results of the analysis
      indicate insufficient utilization of modern available diagnostic methods. Apart
      from clinical assessment the main basis for diagnosis of tuberculosis was A-P
      radiography. Tomography examination was performed in 35.5% of patient only,
      bronchoscopic in 19.8% and cytologic examination of sputum in 15.9%.
      Bacteriological examinations during the first phase of diagnosis, usually in
      hospitals, were satisfactory. Error in diagnosis was found in 63 patients, i.e.
      11.3% of cases. The treatment in patients considered as correctly diagnosed, was
      in the intensive phase correct, but in the continuation phase--too long.

PMID- 9658877
TI  - [Analysis of diagnostic errors and recommendations of diagnostic procedures in
      bacteriologically negative pulmonary tuberculosis].
AB  - The paper presents a detailed analysis of errors in the diagnosis of
      bacteriologically negative pulmonary tuberculosis in a random sample of 560
      patients out of all such patients registered in 1993. The false diagnosis was
      found in 63 patients i.e. in 11.3% of the sample. Among the 63 patients with
      false diagnosis of tuberculosis there were 15 cases with lung cancer, 15 cases
      with pneumonia and/or pleuritis, 15 cases with disease of circulatory system with
      abnormal radiological of the lungs, 8 cases with old post-tuberculosis changes in
      the lung considered as relapses, 4 cases of bronchiolitis obliterans with
      organizing pneumonia, 3 cases of sarcoidosis and 1 case of aspergillosis in a
      post-tb cavity. The most serious errors were those related to failure in
      diagnosing (or of too late diagnosis) of lung cancer. These failures comprised
      2.7% of patients in the sample. The chance to detect a lung cancer in the sample
      was 2900 cases in 100,000 men and 2200 cases in 100,000 women. This chance was
      much higher than in general population--29x for men and 100x for women. The main
      source of errors was false interpretation of radiological examinations and
      neglect to utilise other diagnostic procedures like bronchoscopy, cytology or
      tomography examinations. As an outcome of the analysis authors present their
      recommendations for diagnostic procedures in the diagnosis of bacteriologically
      negative pulmonary tuberculosis.

PMID- 9658878
TI  - [A new, automatic, non-radiometric system for culturing MB/BACT bacilli and its
      value in the microbiologic diagnosis of tuberculosis].
AB  - The MB/BacT is a fully automated, rapid, non-radiometric system, for the culture
      of Mycobacteria for clinical samples other than blood. CO2 production is measured
      and reported as reflective units from the MB/BacT Process Bottle colorimetric
      sensor. We are evaluating the MB/BacT system in comparison to our routine culture
      method--culture on egg media (glycerol and puruvate), in the Bactec 460-Tb
      radiometric machine and in MB Redox. A total of 286 clinical samples from
      respiratory tract were inoculated into three or four culture systems and
      incubated at 37 degrees C. There was only little difference in mean time to
      detection between the MB/BacT and Bactec system (for M.tuberculosis 11 days
      versus 9 days), but both systems were faster than egg media (16 days).
      Contamination rates for MB/BacT system was 8.4%, and for Bactec 6.9%. The
      colorimetric technology used in the MB/BacT is a rapid and sensitive for the
      measurement of mycobacterial growth.

PMID- 9658879
TI  - [Use of Polymerase chain reaction (PCR) for detection of Mycobacterium
      tuberculosis complex from patient materials].
AB  - The polymerase chain reaction (PCR) and direct culture were applied for detection
      of Mycobacterium tuberculosis complex in samples obtained from patients with
      suspicion of pulmonary and extra-pulmonary tuberculosis. In the reaction of
      amplification IS6110 was applied as a target region, and PCR reaction products
      were of the size of 123 bp and 317 bp. A total of 278 samples (158 sputum, 36
      urine, 25 pleural effusion, 23 bronchial washings, 8 blood, 4 stomach washings, 3
      cerebrospinal fluid, 2 fragments of skin, 2 pleural effusion, and 17 others
      samples) from 181 patients were tested. Mycobacterium tuberculosis complex was
      detected by PCR in 144 out of 278 samples and by culture in 68 of 278 samples.
      The PCR test enabled a rapid and sensitive diagnosis particularly in a number of
      samples which were negative on culture.

PMID- 9658880
TI  - [Usefulness of redux properties in acid-resistant bacilli for rapid detection of
      their growth in culture].
AB  - MB REDOX a new system for detection of Mycobacterium is described. It is a
      modified, serum supplemented Kirchner-medium containing a colourless tetrazolium
      salt reduced by the redox system used for self-indicating microbial growth. In
      this study we have tested sensitivity and time of isolation of Mycobacteria in MB
      REDOX and compared to the other different systems of cultivation.

PMID- 9658881
TI  - [The influence of rifampicin on selected parameters of immunologic response].
AB  - Rifampicin (RMP), antituberculous drug, has been controversially described for
      many years as an immunosuppressant. The goal of this work was to determine the
      influence of RMP on selected parameters of the immune response in vivo and in
      vitro. In vivo (in B6AF1 mice) the influence of long-term treatment on primary
      humoral response and cellular response was evaluated. Drug dose was 50 mg/kg. In
      vitro (using peripheral blood of volunteers) the influence of RMP on mitogen
      induced proliferation, metabolic activity of granulocytes and leukocyte induced
      angiogenesis by diverse subpopulation of mononuclear cells was examined. The
      concentrations tested were 7 and 70 micrograms/ml. RMP slightly stimulated
      production of anti-SRBC antibodies and suppressed cellular response in mice,
      decreased PHA and ConA induced proliferation in higher concentration and strongly
      inhibited chemiluminescence at concentration used. RMP inhibited also leukocytes
      induced angiogenesis.

PMID- 9658882
TI  - [Changes in the respiratory system of patients with rheumatoid arthritis-
      personal observations].
AB  - 13 patients with RA admitted to our Institute with symptoms of respiratory
      involvement were described. Taking under consideration pulmonary function tests,
      radiological findings and histological examinations, we recognised 7 cases with
      interstitial lung disease, 3 cases with recurrent respiratory infection with
      bronchiectasis, 1 case with pleuritis, 1 with Caplan's syndrome and 1 with
      alveolar haemorrhage. The role of RF, and treatment with gold in the development
      of interstitial lung disease, as well as character of physiologic abnormalities
      concerning the small airways and its potential connection with bronchiolitis were
      discussed.

PMID- 9658883
TI  - [Coexistence of obstructive lung diseases and lung cancer].
AB  - Connection between histological type of lung cancer and existence of clinical and
      spirometric symptoms of COPD was analysed in 110 lung cancer patients (64 small
      cell, 23 adenocarcinoma, and 23 squamous). It was shown that adenocarcinoma was
      significantly more frequent among subjects with values of FEV1%VC over 70 than
      among subjects with small cell and squamous lung cancer. Also subjects with
      values of FEV1% VC over 70 had significantly higher oxygen blood pressure, and
      clinical and radiological symptoms of COPD were less intensive than in subjects
      with values of this index below 70. There was no correlation between histological
      type of lung cancer and bronchoscopic symptoms of bronchitis and radiological
      symptoms of emphysema.

PMID- 9658884
TI  - [Cytostatic treatment of patients with advanced non-small cell lung cancer].
AB  - 92 patients with advanced non-small cell lung cancer were treated with cisplatin
      80 mg/m2 day 1 and etoposide 120 mg/m2 on days 1-3. In 58 of them vinblastine 5
      mg/m2 was also applied on days 1 and 3. In 25% of all cases partial response and
      in another 26% minimal regression was found after 2 courses of chemotherapy,
      independently to treatment modality. Partial regression was observed
      significantly more often in patients with adenocarcinoma, but survival time was
      significantly shorter in this group. Median survival time was 8 months for all
      patients, 10 months for stage IIIB and 6 months for stage IV. This difference was
      significant.

PMID- 9658885
TI  - [Analysis of patients registered in outpatient departments for tuberculosis and
      lung diseases in group VI N (neoplastic) during the first half of 1995].
AB  - 2115 cases of chest neoplasms were registered during the first six months of 1995
      in Pulmonary Outpatient Departments in Poland. In 865 (40.8%) patients squamous
      cell cancer was diagnosed, in 344 (16.2%)--small cell lung cancer, in 174 (8.2%)-
      adenocarcinoma, in 107 (5%) other types of lung cancer and in 5.6% of cases--lung
      cancer with undefined histology. Predominated subjects aged from 60 to 69 years
      (43.5%). Lung cancer under 50 years of age was observed significantly more often
      among women (25.8%) than among men (13.5%). Moreover adenocarcinoma was much more
      frequent among women than men and significantly more cases of lung cancer were
      recorded in nonsmoking women. Diagnosis was established during the first 4 weeks
      in 38.9% of patients but 23.6% of patients have waited for it more than 39 weeks.
      Surgical treatment was advised in 16.9% of subjects, radiotherapy in 14.3% and
      26.4% of patients underwent chemotherapy. Treatment analysis was presented
      according histological type of lung cancer. Occupation, performance status,
      clinical stage of the disease, prevalence of cancer in patients families were
      also analysed.

PMID- 9658886
TI  - [Transthoracic needle biopsy under USG control].
AB  - In 114 patients with peripheral lung lesions transthoracic needle biopsy was
      performed under USG control. This method enabled to achieve positive results in
      more than 90% of cases. Transthoracic needle biopsy is a simple diagnostic method
      which allows without serious complications to establish histo-pathological
      diagnosis of thoracic peripheral tumors.

PMID- 9658887
TI  - [A case of binocular blindness in small cell lung cancer].
AB  - A was reported case of binocular blindness associated with small cell lung
      cancer. Most probably this complication was a clinical manifestation of the
      paraneoplastic syndrome. No tumor response was induced with chemotherapy and
      patient died due to tumor progression.

PMID- 9658888
TI  - [Congenital esophago-tracheal fistula in an adult].
AB  - A 33 year old man with recurrent respiratory tract infections was admitted to
      surgery ward. During esophagoscopy and bronchoscopy--esophago-tracheal fistula
      was found. Diagnosis was confirmed by radiologic examination of esophagus.
      Surgical treatment was performed with good result.

PMID- 9658889
TI  - [A case of lipoid pneumonia].
AB  - The 58 years old woman with chronic cough, dyspnea and infiltrations in low area
      of left lung was described. Antibiotics were not effective. Cancer cells were not
      found during bronchoscopy. Explorative thoracotomy was made. Lipoid pneumonia was
      recognised. Just now the patient has completed history: she has taken lipoid
      nasal drops for many years.

PMID- 9658890
TI  - [Oncogenes and suppressor genes in lung cancer].

PMID- 9658891
TI  - [Pulmonary complications of chronic liver diseases].

PMID- 9658892
TI  - [Pulmonary changes in the course of rheumatoid arthritis].

PMID- 9658893
TI  - [Exogenous surfactant preparations].

PMID- 9658894
TI  - [Current trends in prevention and therapy of postmenopausal osteoporosis].

PMID- 9658895
TI  - [Adverse drug reactions in childhood. A drug surveillance study in Sicily].
AB  - The aim of the present study was to investigate the spontaneous reports of
      suspected adverse drug reactions, observed in paediatric patients in Sicily
      during the period between the 1st January 1995 and the 31st August 1997. The ADRs
      were classified according to the "WHO Programme for International Monitoring of
      Adverse Reactions to Drugs". On 1020 reports, the paediatric suspected ADRs were
      130 (12.7%); 23% of these was serious, and 29.2% involved children aged 3 years
      or less. The antimicrobial and the musculoskeletal drugs were responsible of
      74.6% of the whole suspected paediatric ADRs. Cutaneous and gastrointestinal
      apparatus were involved in 70% of reports and were the most frequently targets of
      ADRs. On 57 different molecules ceftriaxone and co-amoxiclav were the most common
      drugs causing ADRs with a percentage of 13%. In 45.4% of ADRs the suspension of
      the treatment occurred, in 34.6% therapy was needed besides the suspension of the
      drug, whilst in 11.5% patients needed an hospital visit. In 59.2% spontaneous
      reports were sent by hospitals, in 32.3% by primary health care and the remaining
      percentage by other sources. Our investigation should stimulate physicians to
      better evaluate the potential side effects of drugs and the cost/effectiveness
      profile of paediatric therapies.

PMID- 9658896
TI  - [Transient immunosuppression after abdominal surgical intervention].
AB  - Transient immunodepression appears a few hours after surgery and usually
      regresses spontaneously within 15-20 days. In this study, cellular and humoral
      immunity parameter values were compared prior to and 24 h, 7 days and 14 days
      after laparotomic and laparoscopic cholecystectomy (12 patients and 25 patients
      respectively) operated at the University of Turin's First Surgical Clinic, to
      look for differences in the immunological effects of these two types of surgery.
      The following parameters were determined: IgG, IgA, IgM, C3, C4, granulocytes
      (CD11c), lymphocytes, B lymphocytes (CD19, CD19-CD15), T lymphocytes (CD3), T
      helper cells (CD3-CD4), T suppressor cells (CD3-CD8), CD4/CD8 ratio, NK cells
      (CD16), monocytes (CD14, CD11c-CD14), IL-2 receptor expression (CD25), HLA-DR
      expression (total HLA-DR, HLA-CD3), total cytotoxic activity (CD57), T cell
      cytotoxic activity (CD8-CD57), and NK cell cytotoxic activity (CD16-CD57).
      Granulocytes increased significantly (p < 0.05) in both groups. The increase was
      more marked in the laparotomy group and still evident on the 7th and 14th days.
      Total T cells, T helpers and NK cells fell after 24 h (p < 0.05) in this group
      only. These results suggest that laparoscopy is associated with less substantial
      immunological changes than laparotomy.

PMID- 9658897
TI  - [An unusual site of bleeding from esophageal varices].
AB  - A case of massive upper gastrointestinal haemorrhage from proximal esophageal
      varices is reported. Upper esophageal varices occur rarely, and serve as
      collaterals in conditions of superior vena cava obstruction. In our patient,
      cervical esophageal varices were associated with portal hypertension due to
      occult liver cirrhosis. As the diagnosis was made at autopsy, this case serves to
      stress the importance of a through examination of the cervical portion of the
      esophagus during routine endoscopy.

PMID- 9658898
TI  - Recurrent Salmonella sepsis and aortitis in a patient with hepatocellular
      carcinoma.
AB  - A 62 years old man was admitted to hospital because of fever; a small superficial
      hepatic nodule was showed by ultrasonography. Blood cultures grew Salmonella
      enteritidis. Cefotaxime was administered for ten days. Fever promptly disappeared
      but one week later recurred with abdominal and back pain. Cultures grew again
      Salmonella enteritidis. Biopsy of the hepatic nodule showed hepatocarcinoma.
      Computed abdominal tomography showed a paraaortic mass. Angiography demonstrated
      hematoma communicating with the aortic lumen. The patient underwent
      revascularization of the involved aortic tract and resection of the hepatic
      nodule. Histology showed suppurative aortic endarteritis and a well
      differentiated hepatocellular carcinoma with a large area of suppurative
      necrosis. The recovery of Salmonella species as of any uncommon bacteria from
      blood should warrant a through research of underlying disease, especially cancer.

PMID- 9658899
TI  - [Patient-gastroenterologist relations: a viewpoint].

PMID- 9658900
TI  - [Esophageal dislocation by aberrant right subclavian artery].

PMID- 9658901
TI  - [Role of abdominal echography in internal medicine].

PMID- 9658902
TI  - [Obsessive-compulsive disorders: clinical forms and comorbidity].

PMID- 9658903
TI  - [Dyspepsia: a reappraisal problem].
AB  - Dyspepsia is a major public problem. It occurs in 25-40% of the general
      population negatively affecting the quality of life. 2-3% of the patients visited
      by the GP and up to 30% of those visited by the gastroenterologist have
      dyspepsia. Both diagnostic procedure and therapy are expensive. Definition,
      aetiology and pathogenesis of the disorder are not clear cut. The aim of this
      review is to outline the main trends in the relevant area of the clinical
      practice. The authors choose the most comprehensive definition among the thirty
      of the medical literature. To rule out, the most commonly and frequently wrong
      opinions risk factors have been examined. The authors distinguished between
      symptoms of function and organic dyspepsia and those of Irritable Bowel Syndrome
      and Gastro-Esophageal Reflux Disease, which often overlap and make difficult the
      management of the patient. The aetiology and pathogenesis have also been
      discussed, with particular emphasis on Hp. Advantages and drawbacks of different
      diagnostic approaches have been investigated. An age and symptoms related
      approach of the cases with dyspepsia is proposed, which allows to manage the
      patient without the necessity of invasive procedures. It is finally suggested
      that are cases which can be managed by the GP and others for whom the
      gastroenterologist intervention is mandatory.

PMID- 9658904
TI  - [Evidence-based medicine. 3. Systematic reviews: a tool for clinical practice,
      permanent education and health policy decisions. Italian Group on Evidence-Based
      Medicine-GIMBE].
AB  - The reviews of research, summarizing a great amount of studies in a manageable
      format, are invaluable tools for physicians, inundated with enormous amount of
      biomedical information. However, narrative reviews are often misleading because,
      mixing together opinions of authors and results of research, the relation between
      clinical recommendation and evidence is partial and based on a biased citation of
      primary studies. In contrast to narrative reviews, the systematic reviews
      assemble, critically appraise, and synthesize the results of primary studies
      addressing a specific topic. Additionally their authors use strategies for
      minimizing bias and random error. The science of systematic reviews is now
      supported by the Cochrane Collaboration, an international network established for
      "preparing, maintaining and disseminating systematic reviews of the effects of
      health care". The authors provide tools for searching, critically appraising and
      using in practice the systematic reviews, which use can help physicians to
      improve the transfer of research in clinical practice, a task obliged by
      limitation of financial resources to physicians of any health service.

PMID- 9658905
TI  - [Approval of clinical trials].

PMID- 9658906
TI  - [Adult respiratory distress syndrome and nitric oxide].

PMID- 9658907
TI  - [Difficulties in the approval of clinical trials in Spain. An obstacle race].
AB  - Time required until approval of clinical trial protocols as well as the more
      common bureaucratic problems were studied. A questionnaire was administered to
      AMIFE members and our experience was analyzed regarding twenty-two multicenter
      clinical trials performed from 1993 to 1996. Payment to centers resulting in
      indirect costs ranged from 10% and 30% relative to the total cost of the study in
      the center and median time to obtain the trial approval was 112 days. Some
      possible solutions to improve the efficiency in the process of protocol approval
      are noted.

PMID- 9658908
TI  - [Acute respiratory distress syndrome: incidence and course in a Spanish ICU].
AB  - We have analyzed the 57 ARDS admitted at the Intensive Care Unit (ICU) of the
      Hospital General Vall d'Hebron of Barcelona in 1996 (the 5.7% of the ICU and the
      0.18% of the hospital admission). We have studied the epidemiological
      characteristics, as well as their ICU complications and mortality. This year was
      the first to have nitric oxide (NO) as complementary treatment in the ARDS
      patients at our hospital. They were 42 males and 15 females, with a mean age of
      60 years, APACHE II 21 and a lung injury score 3.1. The 87% of the patients need
      vasoactive drugs. The 47% need Swan-Ganz catheter to optimize the haemodynamic
      management. The 77% presented a multiple organ disfunction syndrome (MODS) and
      the 56% acute renal failure. The total mortality was 70%, basically due to MODS
      (68%), while due to hypoxemia only in the 22%. The group treated with NO (the 35%
      of the ARDS patients) were younger, without any other differences the patients
      who did not received this treatment and with the same stage and mortality.
      Patients who presented MODS, renal failure or hemodynamic unstableness presented
      a higher mortality (p < 0.05).

PMID- 9658909
TI  - [Prospective study of nosocomial infections in a medical ICU. A proposal for the
      generalized use of the National Nosocomial Infection Surveillance System rates].
AB  - OBJECTIVE: To know the more relevant nosocomial infection (NI) rates in our
      Intensive Care Unit (ICU), risk factors associated with NI and trends in the
      infective flora. METHODS: During a three-month period, the cumulative incidence,
      density of overall incidence and device associated infection rates were
      determined in a total of 308 patients admitted to the medical ICU, following the
      recommendations of the National Nosocomial Infection Surveillance System (NNIS)
      in the USA. RESULTS: The cumulative incidence was 8.4 infections per 100
      admissions. The density of overall incidence was 12.9 nosocomial infections per
      1,000 days of ICU stay. Device-associated infection rates were: 28.9 pneumonia
      per 1,000 mechanical ventilation days, 5.3 urinary tract infections per 1,000
      days of catheter use and 0.4 bacteremia per 1,000 days of central venous
      catheter. Pneumonia was the more common NI, followed by urinary tract infection.
      Pseudomonas aeruginosa was the microorganism recovered most frequently. The most
      common used antibiotics were third generation cephalosporins, followed by
      quinolones and macrolides. CONCLUSIONS: The use of NNIS rates is advisable
      because its allows to know the impact of NI on our unit and to perform
      comparative studies with other units of similar characteristics.

PMID- 9658910
TI  - [Results of aortic valve replacement surgery in patients over 75 years of age].
AB  - The increase in the mean populational age has increased the number of elderly
      people eligible for cardiac surgery. The aortic pathology represents the most
      common valvular pathology, mainly of degenerative etiology. The efficiency of the
      aortic valve replacement in people aged over 75 years was studied, with
      evaluation of hospital mortality, survival and functional class (NYHA). MATERIALS
      AND METHODS: A total of 51 patients (25 males and 26 females, mean age 76.4 years
      [range: 75-83]) underwent aortic valve replacement from October 1989 to February
      1997. The most common condition was aortic stenosis (62.7%), followed by aortic
      insufficiency (19%) and double aortic lesion (17%). Moreover, 31.3% of patients
      required also coronary surgery with a mean of 1.1 grafts per patient. In 13.7% of
      cases surgery on mitral valve was performed (1 commissurotomy, 1 mitral
      prosthesis, 5 valve prostheses). In 10% of patients the procedure had to be
      performed on an emergency basis. The functional class of patients prior to
      surgery was NYHA grade III for 37% and grade IV for 10% of cases. The clinical
      symptoms corresponded to angor in 15 cases (29.4%) and syncope in four cases
      (7.8%). In nine patients the left ventricular ejection fraction prior to surgery
      was below 50%. Aortic bioprostheses were implanted in 86.2% of cases. RESULTS:
      The hospital fatality rate was 13.7% (7 cases). In the univariate analysis the
      following mortality risk factors reached statistical significance: left
      ventricular ejection fraction prior to surgery below 50%, associated surgery and
      size of aortic prosthesis. In the multivariate analysis the following risk
      factors were significant: left ventricular ejection fraction prior to surgery
      below 50% and associated mitral surgery. The follow-up was performed in 100% of
      patients, with a mean time of 29.6 months. One patient died during follow-up. The
      functional class was NYHA grade I in 95.2% of cases. The actuarial survival,
      including hospital mortality, was 84.2% at 5 years. CONCLUSIONS: Despite a higher
      mortality in the aortic valve replacement surgery in patients aged over 75 years
      compared with general population, results, long-term survival and life quality of
      patients, renders surgery a non refusable first option as therapy for aortic
      valve pathology in this age group. Nevertheless, avoiding the deterioration of
      preoperative left ventricular function is imperative, mainly in those cases with
      concomitant mitral pathology, as both factors significantly contribute to an
      increase in mortality in this group.

PMID- 9658911
TI  - [Safety of oral anticoagulation in aged patients with heart diseases].
AB  - BACKGROUND: Anticoagulation therapy in the elderly poses some doubts on the
      possible increase in hemorrhagic risk. The hemorrhagic complications in a
      population of patients over 70 years of age anticoagulated with acenocoumarol by
      heart disease were studied. MATERIALS AND METHODS: A study was made of seventy
      two patients (43 females and 29 males; mean age: 73 years) anticoagulated for one
      year and controlled on an outpatient basis by means of INR (international
      normalized ratio) measurement with a maximal interval of four weeks. INR values
      above 4.5 or below 2.0 were considered out of range. RESULTS: Nineteen patients
      had an INR above the recommended value on one occasion and eleven patients on two
      or more occasions. Sixteen patients had hemorrhagic complications, five were
      admitted on account of hemorrhages although none of them required transfusional
      therapy. No cases of brain hemorrhage or peripheral embolism occurred.
      CONCLUSIONS: Most anticoagulated elderly patients were within their therapeutic
      range. The percentage of severe hemorrhagic complications was low. Advanced age
      had did not prove to be a factor against therapy with oral anticoagulants.

PMID- 9658912
TI  - [Thyroid lymphoma: a not so unusual disease].
AB  - A review was made of the six cases of primary thyroid lymphoma diagnosed at our
      institution. An increase in the incidence was observed of this disease in the
      last two years, with no evidence of lower diagnosis of anaplastic thyroid
      carcinoma. The presenting symptom was compression in all cases. The interval time
      from symptoms to diagnosis ranged from 5 to 150 days. The centroblastic pattern
      was the most common histologic type, with a relevant role of MALT lymphoma in the
      last few years. Therapy included surgical exeresis in two cases on account of
      compressive symptoms and radiotherapy and/or chemotherapy was always preferred on
      account of the stage.

PMID- 9658913
TI  - [Hepatitis C in health personnel].

PMID- 9658914
TI  - [Thyroid cancer: metabolic treatment and follow-up using thyroglobulin levels and
      I-131 gammagraphy].

PMID- 9658915
TI  - [Proliferative glomerulonephritis and dyspnea in a 70-year-old male patient].

PMID- 9658916
TI  - [Correction of drug dose in patients on hemodiafiltration].

PMID- 9658917
TI  - [Abdominal pain in a young man].

PMID- 9658918
TI  - [Adult respiratory distress syndrome with fatal outcome after status
      asthmaticus].

PMID- 9658919
TI  - [Young woman with tuberous sclerosis and spontaneous pneumothorax].

PMID- 9658920
TI  - [Digital gangrene, osteomyelitis and pneumonia in a young parenteral drug abuser
      female patient].

PMID- 9658921
TI  - [Hyperkalemic myopathy and Addison's disease].

PMID- 9658922
TI  - [Hypertensive crisis and vesical mass].

PMID- 9658923
TI  - [Pseudomyotonia as initial manifestation of primary hypothyroidism].

PMID- 9658924
TI  - [Macroangiopathic anemia secondary to aspergilloma associated with idiopathic low
      CD4 syndrome].

PMID- 9658925
TI  - [Wernicke's encephalopathy: an alternative diagnosis in oncologic patients].

PMID- 9658926
TI  - [Rendu-Osler-Weber disease. Nontraumatic hemothorax and pulmonary sarcoidosis].

PMID- 9658927
TI  - Spontaneous cytokine gene expression by cultured skin fibroblasts of systemic
      sclerosis. Correlation with collagen synthesis.
AB  - OBJECTIVE: To investigate the spontaneous cytokine gene expression in fibroblasts
      from patients with diffuse cutaneous systemic sclerosis. Their pattern of
      expression was correlated with the production of collagen. METHODS: Fibroblasts
      were obtained from skin biopsies of nine patients diagnosed with systemic
      sclerosis (mean 16 +/- 8.7 years of disease duration) and ten control
      individuals. The cytokine gene expression was detected by coupled reverse
      transcriptase polymerase chain reaction for interleukins 1 beta, 6, 8, tumour
      necrosis factor-alpha, and transforming growth factor beta. In addition, collagen
      synthesis was measured by [14C]-proline uptake in fibroblast cultures. RESULTS:
      All fibroblast samples from patients expressed the interleukin-6 gene (p = 0.04
      compared with controls). Eight of the nine patients expressed interleukin-8 (p =
      0.02 compared with controls). Four of them expressed also transforming growth
      factor beta and two more weakly expressed the tumour necrosis factor-alpha gene.
      Only one patient showed transcription for the interleukin-1 beta gene. In
      accordance with such immune activation, collagen synthesis was higher in
      fibroblasts from patients with systemic sclerosis (p = 0.028) as compared with
      normal controls. Indeed, a positive correlation was found between the expression
      of IL-6 gene and collagen production (rs = 1). CONCLUSION: The constitutive
      expression of IL-6 and IL-8 genes by fibroblasts may play an important role in
      the perpetuation of local immune dysregulation, thus leading to a permanent
      fibroblast activation in patients with systemic sclerosis.

PMID- 9658928
TI  - [Risk factors in the epidemic neuropathy of Cuba].
AB  - OBJECTIVE: A case control study to find out if Cuba's epidemic neuropathy was a
      result of one of the following causes: (1) an infectious process, (2) exposure to
      one or more toxical agents, (3) low intake of one or more nutrients, or (4) more
      than one of such causes and their interactions. MATERIAL AND METHODS: A total of
      311 cases of epidemic neuropathy with optic and peripheral symptoms and 377
      controls were studied. A questionnaire with 55 items was employed to document
      exposure to factors determined by the etiologic hypothesis. Data analysis was
      done separately for the optical and peripheral types of the disease. RESULTS: No
      association was found between illness and any deficiency of basic sanitation for
      both types of neuropathy. Acute stress, irregularities in food intake, body
      weight loss in the last 12 months and other indicators of nutritional
      deficiencies were associated to both clinical manifestations, although they were
      also high in the controls. Low frequency of illness was found for people living
      with diseased persons. Females had a significant high risk of illness in the
      peripheral manifestations whereas smoking was the only toxical risk factor in
      optical neuropathy. Nutritional deficiencies together with unidentified personal
      factors were the main associations for illness outcome; smoking increased
      significantly the risk of optical neuropathy. CONCLUSIONS: 1. The infection
      etiology was unsupported in the study. 2. Smoking appeared as a factor for the
      optical neuropathy. 3. Stress induced by vital events were significantly
      associated with the disease. 4. Both types of the neuropathy were associated to
      body weight loss and other indicators of nutritional deficit.

PMID- 9658929
TI  - [Vitamin D induces proliferation in rat endometrium cultured cells].
AB  - OBJECTIVE: To study the effects of 1,25-dihydroxyvitaminD3 (1,25-(OH)2D3) on
      proliferation and cell death in the rat uterus. MATERIAL AND METHODS: A rat
      endometrial cell line (Rentro 1) grown in a Dulbecco Minimal Essential Medium
      (DMEM) supplemented with 1% charcoal stripped serum was used in all experiments
      in order to eliminate the steroid hormone. Cell monolayer was incubated in the
      presence and absence of 1,25-(OH)2D3 or 17 beta-estradiol or vehicle. After
      stimulation, we evaluated cell proliferation and DNA synthesis by trypan blue
      counting method and flow cytofluorometry, respectively. Finally, the genomic DNA
      integrity was evaluated by electrophoresis and the bands visualized with
      ultraviolet light. RESULTS: The cells in medium containing 1% fetal bovine serum
      free of steroid hormones stimulated the cell growth 85% more than without serum.
      Supplement with albumin did not allow cell growth. The cells did not respond to
      17 beta-estradiol but the presence of 1,25-(OH)2D3 induced cell proliferation.
      These results confirm that Rentro 1 cells do not express the estrogen receptor
      and demonstrate their capacity to respond to 1,25-(OH)2D3. Finally, the integrity
      of DNA was not affected by 1,25(OH)2D3, suggesting that this hormone is not
      involved in cell death by apoptosis in our cell line, as seen in other cell
      lines. CONCLUSIONS: 1) 1,25-dihydroxyvitamin D induced cell proliferation in the
      endometrial cell line Rentro 1 in a dose-dependent fashion and this effect is
      independent of the presence of an estrogenic stimulus; 2) the increase in cell
      number was related to DNA synthesis during the cell cycle; and 3) the presence of
      the hormone in the culture medium was not able to induce cell death.

PMID- 9658930
TI  - [Anemia and iron deficiency in 490 Mexican pregnant women].
AB  - OBJECTIVE: To explore correlations of sociobiological variables with levels of
      blood hemoglobin (HB) in 490 pregnant women. SETTING: Women attending private
      practice and two public hospitals in the city of Leon, State of Guanajuato (1800
      m above sea level). MATERIAL AND METHODS: Demographic, obstetric, nutritional and
      socioeconomic data were obtained together with an EDTA-blood sample for CBC, and
      serum for metabolite assays. The women had a mean gestation of 25 weeks (range 4
      40) and 65% were multiparous with a mean parity of 2.1. By Mexican standards they
      had fairly high social, nutritional and intergenesic lapse. Associations were
      explored by step-wise multiple ANOVA. RESULTS: On the basis of HB < 12 g/dL
      (equivalent aprox to 11 at sea level), 37% of the women were considered anemic.
      The MANOVA (excluding iron deficiency) showed associations of HB with gestation
      (p < 0.001) and parity (p = 0.024). Iron deficiency was present in 76% of the
      anemics (136/180) and 31% of the non-anemics (97/310). Folate and vitamin B12
      assays in women with anemia and no iron deficiency showed folate or B12
      deficiency in only 33% (14/43) leaving 29 cases with anemia of unknown etiology.
      CONCLUSIONS: 1. Gestation age was the factor most strongly associated to anemia
      and iron deficiency in our sample. 2. Anemia and iron deficiency were seen in 37%
      (N = 180) and 48% (N = 233) of the women respectively. 3. Of the 180 anemic
      women, 76% (N = 136) were iron deficient but only 14/43 anemic without iron
      deficiency were folate or B12 deficient leaving 6% (29/490) with anemia of
      unknown etiology. 4. The prevalence of anemia and iron deficiency were high in
      our population in spite of its fairly good sociodemographic and nutritional
      conditions.

PMID- 9658931
TI  - [Laparoscopic splenectomy in autoimmune thrombocytopenic purpura].
AB  - OBJECTIVE: To describe the perioperative characteristics, complications and
      outcome of the first 22 patients who underwent laparoscopic splenectomy for
      refractary/recurrent ITP in our institution. MATERIAL AND METHODS: Clinical and
      biochemical characteristics, spleen size, indication for surgery, operative time,
      blood requirements, complications and outcome of 22 patients who underwent
      laparoscopic splenectomy between 1994 and 1997 were prospectively recorded. Their
      mean age was 40 +/- 15 (+/- SD), 15 females and 7 males. RESULTS: The
      preoperative platelet count was 56 thousand +/- 58.7/uL, average spleen size 10.5
      +/- 2 cm. The surgical time averaged 4.5 +/- 1 hours; accessory spleens were
      removed from two patients. Conversion to the open procedure was necessary in two
      cases. Complete response was achieved in 59%, partial response in 27%, and no
      response in 14% (none of these due to missed accessory spleens). Six patients
      developed complications. One of them died two days after surgery. The mean
      postoperative stay was 4.7 +/- 2.6 days. CONCLUSIONS: The results of laparoscopic
      splenectomy were similar to our previous results with the open approach. The
      laparoscopic technique took longer in our hands but the postoperative stay was
      shorter.

PMID- 9658932
TI  - [Survey of climacteric symptoms in semi-rural areas of Yucatan].
AB  - OBJECTIVE: To determine the symptoms of climacterium in women from rural areas of
      Yucatan. MATERIAL AND METHODS: We conducted a transversal study of 202 women in
      the villages of Seye and Cuzama. A questionnaire on socioeconomic status, and
      symptoms of the menopause was applied. RESULTS: In both villages, the commonest
      menopause-related symptoms were backache tiredness in more than half of the
      women. Sweating and hot flashes were reported by 35% and 31%, respectively.
      CONCLUSION: Our observations differed from the absence of hot flashes and
      sweating reported by another group in rural women living in Yucatan (Ref 7).

PMID- 9658933
TI  - [Otoneurologic abnormalities in insulin-dependent diabetes].
AB  - OBJECTIVE: To assess the auditory and vestibular function in patients with
      diabetes. MATERIAL AND METHODS: We studied and followed for three years, 10
      patients (6 females) of 20.6 years of age (SD 5.5 years), with insulindependent
      diabetes mellitus of 9.5 years (SD 3.7 years). The patients were selected for
      having peripheral neuropathy without prolipherative retinopathy and otologic
      disease or individual factors which could cause neurootologic symptoms. Their
      glomerular filtration rate and renal plasma flow were 150 mL/min (SD 50) and 543
      mL/min (SD 113). RESULTS: Initially all patients had normal audiologic responses,
      including auditory brainstem responses, but had abnormally and simetrically
      diminished horizontal vestibulo-ocular responses. A year later one patient had
      vertigo and asymmetric vestibulo-ocular responses. In the third year, another
      patient showed similar abnormalities and a third one showed sensorineural hearing
      loss. CONCLUSION: Our results suggest that patients with insulindependent
      diabetes mellitus may suffer neuro-otological deterioration.

PMID- 9658934
TI  - [Observer variability in the radiologic interpretation of interstitial lung
      disease].
AB  - OBJECTIVES: To study intra and interobserver variability of two pediatric
      neumologists in X-ray readings of interstitial lung disease (ILD), to determine
      the effect of clinical data on the readings, and to evaluate their interpretation
      in terms of the histopathology diagnosis. DESIGN: Prospective, cross sectional,
      comparative, blinded. SETTING: The Instituto Nacional de Pediatria of Mexico
      City. MATERIAL AND METHODS: Chest X-rays of 45 ILD pediatric patients with
      diagnosis confirmed by open lung biopsy were read by the two observers three
      times at two weeks intervals and in a randomized fashion. The observers were
      blinded to previous readings of both observers as well as to the diagnosis. The
      first two readings were done with no clinical information given to the observers,
      but some was given for the third reading (age of inception, length of evolution,
      and main symptoms at time of the X-rays). A classification in one of 5 patterns
      (lineal, reticular, reticulonodular, grounded glass, honeycomb) was established
      by the observers. Associations of patterns with anatomopathological diagnosis was
      explored. Weighted kappa was used in the statistical analysis. RESULTS: With one
      exception, good agreement (Kw 0.57-0.88) was found intra and interobservers.
      CONCLUSION: We believe the low variability is the result of the 15 years of
      shared experience of the two observers participating in this study.

PMID- 9658935
TI  - Two cases of psychogenic purpura.
AB  - Psychogenic purpura, also known as recurrent painful bruising or autoerythrocyte
      sensitization syndrome (Gardner-Diamond syndrome) is usually associated with
      emotionally disturbed patients. It is a troublesome entity for both patient and
      physician since extensive work-ups yield no diagnosis. We describe two females in
      their early twenties with recurrent painful bruising and diverse accompanying
      symptoms which appeared after physical trauma. One of the patients developed a
      bruise after intradermal injection of her own blood (with no reaction to saline
      injection). One patient had a personality (borderline) disorder, the other a
      factitious disorder. Punch biopsies revealed a perivascular inflammatory
      infiltrate, erythrocyte extravasation and no vasculitis. Psychogenic hemorrhagic
      disorders are uncommon yet must be considered in the differential diagnosis of
      purpura. Patients are usually young emotionally troubled females who present
      painful recurrent bruises on extremities frequently after trauma or surgery.
      Autoimmune mechanisms and increased cutaneous fibrinolytic activity have been
      implicated, although further studies are needed. Correct diagnosis is important
      to avoid aggressive and even mutilating treatments, and an adequate comprehension
      of these purpuras is important for the attending physician.

PMID- 9658936
TI  - [Ten cases of Ciguatera fish poisoning in Yucatan].
AB  - BACKGROUND: Ciguatera fish poisoning is a clinical syndrome associated with the
      consumption of contaminated fish. The clinical picture is a constellation of
      gastrointestinal, neurologic and cardiovascular symptoms. AIM: To report 10 cases
      of ciguatera poisoning in our country. METHOD: We recorded the clinical course
      during the severe acute symptoms with a follow up of 34 months. RESULTS: The time
      between the ingestion of contaminated fish and symptoms varied from 20 minutes to
      12 hours. All suffered gastrointestinal disturbances as the main manifestation.
      Watery diarrhea was the earliest complaint. Cold-to-hot temperature reversal
      dysesthesia occurred in all but there were differences in the occurrence of
      nausea, vomiting, cramping, abdominal pain, weakness, paresthesia, arthralgia,
      myalgia, dizziness, dysuria, dyspnea, headache, pruritus, lip numbness, dry
      mouth, dental pain, chills, tremors, fasciculations, blurred vision,
      hypersalivation and dysphagia. CONCLUSION: 1. There were some differences in the
      clinical picture of our cases mainly in the initial symptoms and their severity.
      2. Gastrointestinal symptoms were the most common complaint. 3. We did not find
      associations between the amount of toxic fish ingested with the latency period
      and the severity and duration of the symptoms.

PMID- 9658937
TI  - [Two cases of colonic lipoma as a cause of rectal prolapse].
AB  - Two cases of submucosal colonic lipomas presenting as rectal prolapse are
      described. Both of them required resection by laparotomy. Colonic lipomas are a
      uncommon entity and they have not been documented as a cause of rectal prolapse.

PMID- 9658938
TI  - [The genetics of Alzheimer's disease].
AB  - Alzheimer's disease is a degenerative disorder of the central nervous system
      which causes progressive memory and cognitive decline during mid to late adult
      life and is accompanied by a wide range of neuropathologic features including
      extracellular amyloid plaques and intra-neuronal neurofibrillary tangles. Four
      genetic loci for Alzheimer's disease have been identified. They are the amyloid
      precursor protein gene on chromosome 21, a gene for early onset autosomal
      dominant form on chromosome 14, another gene on chromosome 1, and the risk
      modifying gene apolipoprotein E on Chromosome 19. The etiology is heterogeneous
      and complex, and additional Alzheimer's disease genes remain to be found. The
      genes identified in the inherited forms are now being used to understand the
      pathogenesis of the disease.

PMID- 9658939
TI  - [Abnormal hemoglobins and thalassemias in Mexico].
AB  - The distribution of abnormal hemoglobins in Mexico is derived from surveys and
      from the study of patients with hemolytic anemia. In aboriginal populations, more
      than 3,000 individuals have been studied: structural abnormal hemoglobins are
      virtually absent in Mexican Indians and the sporadic finding of hemoglobin S
      among them is due to admixture with Africans brought as slaves during the Spanish
      domination; two new variants of hemoglobin (Mexico and Chiapas) were found in
      aborigines. The surveys in hybrid groups in selected areas of the country show
      that in some West and East Coast communities there are different frequencies of
      Hb S heterozygous, and that a high prevalence of Hb S trait has been found in
      some communities similar to that in some African areas. In a group of 200
      subjects of a town located along the Gulf of Mexico Coast, 6% of Hb S and 15% of
      thalassemia beta heterozygous is observed. In hospital surveys in two cities
      (Guadalajara and Puebla) several abnormalities of hemoglobin have been identified
      (C, SC, Riyadh, Baltimore, Tarrant, Fannin-Lubbock and Mexico). In the study of
      isolated cases, mainly of patients with hemolytic anemia, hemoglobins I
      Philadelphia, G-San Jose and D-Los Angeles are seen. The thalassemias are the
      more frequent hemoglobin abnormalities in selected populations of our country. In
      a community of Italian ancestry a frequency of 1.3% of beta thalassemia trait is
      found. In our laboratory, 76% of the abnormalities are cases of beta thalassemia
      trait. Patients with Hb H disease, beta thalassemia (homozygous and heterozygous)
      and combinations of these abnormalities with hemoglobins S, Hb S + hereditary
      persistence of fetal hemoglobin (HPFH) and Hb E as well as families with delta
      beta thalassemia, HPFH and Hb Lepore-Washington-Boston have been also detected.

PMID- 9658940
TI  - [Genetic heterogeneity and phenotypic variability in 46,XY sex reversal].
AB  - The discordance between the chromosomic and the gonadal-phenotypic sex is known
      as sex reversal (XX males and XY females). We review the XY pure gonadal
      dysgenesis characterized by female phenotype, primary amenorrhea and absence of
      secondary sexual development. Bilateral streak gonads are always present in the
      complete form of this syndrome, while variable degrees of virilization are found
      in the partial forms, depending on the severity of the testicular damage. A
      plausible explanation for this pathology are SRY mutations that interfere with
      the testicular differentiation. However, only 10-15% of the patients with the
      complete form show SRY mutations, particularly in the HMG box. The remaining
      cases are probably due to mutations in different autosomal or X-linked genes
      which are also involved in the sex differentiation cascade. Recently, it has been
      shown that mutations in several genes responsible of well known genetic entities
      as WT1, SOX9, DSS and SF1, result in sex reversal. These findings reveal the
      genetic heterogeneity and clinical variability of XY sex reversal and provide the
      basis establishing a hierarchy of genes and their participation in the sex
      determination pathway.

PMID- 9658941
TI  - [The difficulties of scientific journals in Spanish].

PMID- 9658942
TI  - [Experimental endocarditis. Pathological anatomy of human endocarditis].
AB  - Experimental reproduction of human endocarditis in animal models has been based
      on the induction of structural lesions in valve endocardium using different
      methods. The primary lesion caused in this way is the so called non-bacterial
      thrombotic endocarditis. Its colonization is then induced by inoculation of
      microorganisms in the bloodstream. Freedman's modified method has been the most
      widespread model of this type. It has mainly been performed in rabbits with
      inoculation of Staphylococcus aureus or alpha-hemolitic Streptococcus.
      Experimental models of endocarditis have contributed to our knowledge of the
      pathogenic mechanisms, causative agents and predisposing factors of endocarditis.
      They have also allowed us to develop appropriate diagnostic, therapeutic and
      prophylactic measures for its management.

PMID- 9658943
TI  - [Etiopathogenesis of infective endocarditis: predisposing heart diseases and
      causal microorganisms].
AB  - Infective endocarditis is caused by the infection of an amorphous mass of
      platelets and fibrin (the so-called nonbacterial thrombotic endocarditis) which
      involves a damaged endothelial surface of the heart. Several pathogenetic
      mechanisms (hemodynamic, immunological, microbiological, etc.) are needed for the
      development of endocarditis. We review some of these mechanisms, as well as
      possible changes in etiopathogenesis of this disease that have recently occurred.

PMID- 9658944
TI  - [Clinical manifestations of infective endocarditis].
AB  - Infective endocarditis has a broad clinical picture, with systemic and multiorgan
      impairment. The organs most frequently involved are the heart, the central
      nervous system and the kidneys. Complications are caused by several mechanisms:
      direct effect on the heart, septic embolisms and immunological phenomena. We
      review some of the main clinical aspects of this disease, as well as the results
      of a wide series of patients with infective endocarditis from our hospital.

PMID- 9658945
TI  - [Laboratory control in diagnosis and treatment of infective endocarditis].
AB  - Infectious endocarditis is caused by a wide variety of microorganisms.
      Etiological diagnosis depends either on direct methods, directed to the detection
      and isolation of the causative organisms, or serological methods. Blood cultures
      remain as the best method for the diagnosis of bacterial endocarditis. Blood
      culture technology has changed due to the appearance of new automatic continuous
      monitoring systems which shorten the detection time. Endocarditis with a negative
      blood culture has decreased below 5% because of new blood culture systems, new
      serological methods and molecular technology. The control of antimicrobial
      therapy in endocarditis must be performed by expert laboratories. A minimal
      bactericidal concentration, serum levels of antimicrobials and the serum
      bactericidal test are the most useful parameters. Their execution requires the
      use of strict protocols and interpretation must be carried out with an expert in
      clinical microbiology and infectious diseases.

PMID- 9658946
TI  - [Diagnostic criteria of infective endocarditis: from Von Reyn to Duke.
      Transthoracic and transesophageal echocardiography].
AB  - The Von Reyn criteria determine only a small number of definitive diagnoses of
      infectious endocarditis, while it is mainly diagnosed by histopathological
      confirmation in surgery or autopsy. This necessitates carrying out a new
      diagnostic scheme with accurate sensitivity and specificity based on rigorous
      clinical support. This scheme is provided by the Duke University criteria, which
      enhance the role of conventional and transesophageal echocardiography, in the
      diagnosis of infectious endocarditis. Echocardiography is the only accurate
      procedure for a non invasive diagnosis of vegetation, the main lesion in this
      pathology. Often, tissue destruction causes regurgitation, which is responsible
      for hemodynamic impairment or allows the spread of the infectious process to
      perivalvular tissue and can form an abscess. These complications and many others,
      which are difficult to treat, require an early diagnosis of this disease.
      Sensitivity of transesophageal technique to detect vegetations and complications
      is higher than that observed in conventional echocardiography, above all in
      patients with prosthetic valves. If the transesophageal study is negative, the
      existence of an infectious endocarditis is quite unlikely. Nevertheless, we need
      to consider clinical features, as the specificity of this technique is moderate.

PMID- 9658947
TI  - [Natural history and prognosis in infective endocarditis].
AB  - The natural history and prognosis of native valve infective endocarditis,
      prosthetic endocarditis and right sided endocarditis in drug addicts is analyzed.
      In native endocarditis mortality during the active phase is 12% and survival at
      10 years 81%. Early prosthetic endocarditis has a worse prognosis. In late
      prosthetic valve endocarditis prognosis depends on the infective organism:
      mortality is less than 10% in estreptococcal infections and higher than 50% in
      staphylococcal infections. Right sided endocarditis in intravenous drug addicts
      has a relatively benign prognosis and seldom requires surgical treatment.

PMID- 9658948
TI  - [Is prophylaxis needed? Is it really effective? Risk of endocarditis after heart
      surgery].
AB  - Infective endocarditis still has an important morbidity and mortality in the
      acute phase and also in the following years. Because of this, the development and
      use of preventive strategies have been an important target in developed
      countries. Until we have some prospective studies their use will be only
      intuitive and based on the following criteria: endocarditis frequently follows a
      bacteremia; some diagnostic or therapeutic procedures cause bacteremia; the germs
      are habitually predictable in each procedure and are sensitive to specific
      antibiotics; patients with some cardiac or major structural defects have a higher
      risk of endocarditis. For these reasons, a rational treatment is to give the
      specific antibiotic against the microorganism prophylactically before it enters
      the bloodstream during the procedure. Although available data are inconclusive
      and sometimes even contradictory, most authors recommend the indication of
      prophylactic measures whose efficacy depends on three basic points: a)
      identification of patients with a high risk of endocarditis, especially those
      with a prosthetic cardiac valve; b) knowledge of procedures that need
      chemoprophylaxis, especially dental and oral procedures, and c) selection of the
      best prophylactic policy in each specific case. In summary, it is necessary to
      know to "whom", "when" and "how" to apply prophylactic measures. There are some
      special situations that must be considered carefully: patients treated with
      anticoagulant drugs or with a cardiac pacemaker or with an implanted
      defibrillator, patients with renal insufficiency and an arteriovenous fistulae,
      and some patients needing open heart surgery, or those who have already had open
      heart surgery. In conclusion, the prevention of bacterial endocarditis using
      antibiotics is currently practiced in clinical settings, especially in some
      specific groups of patients. It is necessary to recommend this treatment in high
      risk patients (i.e. in those with prosthetic cardiac valves) before a high risk
      procedure (i.e. dental procedures known to induce gingival or dental bleeding,
      including professional cleaning) and in medium risk patients, the indication must
      always be based on an individual analysis according to American Heart Association
      guidelines.

PMID- 9658949
TI  - [Drug treatment of native valve infective endocarditis in patients not addicted
      to parenteral drugs].
AB  - Infectious endocarditis is an infection that is characterized by the presence of
      microorganisms in dense populations in vegetating lesions in the endocardium.
      Because phagocyte penetration to the interior of the vegetation is practically
      impossible, to cure infectious endocarditis, high doses of bactericidal
      antibiotics are administered, usually intravenously and for a long duration. In
      this article, antibiotic treatment is reviewed, depending on the isolated
      microorganism and in cases where necessary, treatment is initiated in an
      empirical manner. Once the microorganism was isolated, the recommended guidelines
      for antibiotic treatment have gone through some variations in recent years, due
      to the changing pattern of antibiotic sensitivity of some microorganisms, to the
      point of finding ourselves on occasion without an effective treatment (e.g.
      multiresistant enterococci). In addition, these variations are due to the
      introduction of new antibiotics that allow, in special cases, for the treatment
      to be administered on an outpatient basis. Using anticoagulation in infectious
      endocarditis is still considered controversial. In general, only patients having
      cardiac valvular prostheses seem to benefit from its use.

PMID- 9658950
TI  - [Prosthetic valve endocarditis].
AB  - Infective endocarditis occurs in 4% of prosthetic valve carriers. The infection
      is related to both the injured endocardium and circulating microorganisms. Early
      prosthetic endocarditis, occurring in the first 12 months after valvular surgery
      is mainly caused by staphylococci, and late prosthetic endocarditis has a similar
      etiology as native valve endocarditis. Clinical manifestations of early cases are
      due to both bacteremia and prosthetic malfunction. In late cases the clinical
      picture is similar to native valve disease. Mortality in prosthetic endocarditis
      remains high, especially in early cases, despite combined medical and surgical
      treatment.

PMID- 9658951
TI  - [Infective endocarditis in the aged].
AB  - This paper reviews the current questions and the new aspects related to Infective
      Endocarditis in elderly patients. Four points are emphasized: a) epidemiological
      changes during the last decades, b) clinical features and diagnostic challenges
      of infective endocarditis in the elderly, c) mortality and prognosis, and d)
      preventive and therapeutic measures that must be taken into account.

PMID- 9658952
TI  - [Endocarditis in parenteral drug addicts. Right-sided endocarditis. Influence of
      HIV infection].
AB  - Infective endocarditis is a life-threatening infective complication in parenteral
      drug abusers. The tricuspid valve is the structure most frequently affected and
      Staphylococcus aureus the predominant microorganism. Fever, multiple pulmonary
      emboli and sustained bacteremia by S. aureus are signs of clinical alert for
      right-sided endocarditis in these patients. Echocardiography has developed a
      significant improvement in diagnosis and the transthoracic mode has a
      considerable reliability when high suspicion is established. Outcome is usually
      favourable with mortality less than 10%. Recent studies have made shorter
      treatments possible in selected patients and oral therapy is also considered. HIV
      infection, in advanced status, may indicate a worse survival rate.

PMID- 9658954
TI  - [Indications and surgical techniques in the acute phase of infective
      endocarditis].
AB  - Infectious endocarditis is increasingly resistant to antibiotic therapy, due to
      the increasing number of patient with cardiovascular prostheses or those who are
      severely immunosuppressed. Frequently, this syndrome and its complications can
      only be solved with surgery. In this article, which is based on the international
      literature plus own observations in 77 patients, the indications for surgery and
      the different technical approaches during the acute phase of infectious
      endocarditis are reviewed. Surgery to control infectious endocarditis is
      indicated when there is one of the following situations: a) persistence of
      infection despite an adequate antibiotic treatment, usually due to a specific
      pathogen (Staphylococcus aureus, fungus, etc.) or to a low antibiotic penetration
      into the infected issues (abscess); b) progressive hemodynamic deterioration due
      to tissular destruction and development of valvular incompetence or fistulous
      communications or c) development of other complications (repetitive embolism,
      cardiovascular aneurysms, conduction blocks, etc.). Hemodynamic deterioration due
      to heart failure refractory to medical treatment is the most frequent indication
      for cardiovascular surgery, and this was present in 61% of our patients. The
      timing for surgery is still controversial, although scheduling it at an early
      stage is generally preferred. The specific surgical technique is chosen according
      to the degree of tissular destruction and is aimed to remove the infected tissue
      and to repair the damaged structures or, if this is not feasible, to implant
      cardiovascular prosthesis.

PMID- 9658953
TI  - [Infective endocarditis caused by unusual microorganisms].
AB  - All series of infective endocarditis had a variable proportion of cases without
      an etiologic agent because all cultures were negative. New microbiologic
      techniques have permitted the discovery of the role of many microorganisms in
      infective endocarditis. C. burnetii is an increasing causative agent of subacute
      infective endocarditis. In the diagnosis, to the detection of antiphase-I
      antibodies, immunohistochemical, molecular techniques and cellular cultures have
      been added. Total cure is difficult to obtain. The combination of doxicicline
      plus ciprofloxacin for at least 3 years has been proposed as the treatment of
      choice. Surgery must be reserved for patients with cardiac insufficiency. Less
      than 2% of cases of acute brucellosis are complicate with infective endocarditis.
      Infective endocarditis produces serious and rapid valvular destruction with high
      mortality rates if valve surgery is not performed. For medical treatment at least
      3 active agents are required. Bartonella has recently been described as an
      etiologic agent of infective endocarditis. It mainly affects to homeless people
      living in poor hygienic conditions. The aortic valve is most commonly involved
      and, frequently, valve insufficiency requires valve replacement. Blood culture
      isolation needs long incubation periods. Parenteral nutrition, immunosuppression,
      wide spectrum antibiotic regimens, intravenous drug addiction and cardiovascular
      surgery are risk factors previously described in the development of fungal
      endocarditis. C. albicans and Aspergillus spp. are most frequent etiologic
      agents. Infective endocarditis should be suspected in any patient with systemic
      fungal disease. Blood cultures are often negative except for Candida spp.
      Peripheral emboli and large vegetations are frequent. Mortality is high,
      antifungal therapy combined with surgery is the treatment of choice. Legionella,
      Mycoplasma, Chlamydia, Mycobacteria, viruses are potential agents of infective
      endocarditis, and difficult to diagnose because of special culture requirements.
      Epidemiological clues, serologic and molecular techniques and blood cultures
      could identify them.

PMID- 9658955
TI  - [Aortocoronary bypass without extracorporeal circulation].
AB  - Extracorporeal circulation is nowadays part of the standard technique of
      aortocoronary reconstruction. The authors summarize in their paper their
      experience with operations in 45 patients where an aortocoronary bypass was made
      on the beating heart without the use of extracorporeal circulation. None of the
      patients died. The incidence of postoperative complications was low. Rapid
      rehabilitation of the patients and a shorter period of hospitalization makes this
      method an alternative standard technique of aortocoronary reconstruction.

PMID- 9658956
TI  - [The clinical picture of acute appendicitis in children].
AB  - The authors describe 3860 child patients operated on account of acute
      appendicitis and analyse the data with regard to age, sex, year of incidence and
      surgical finding. The highest incidence of acute appendicitis is between 8 and 11
      years with a peak at the age of 10 years. It is more frequent in boys (58.3%)
      than in girls (43.7%), the ratio being 1.3:1. It occurs more often during the
      cold months (46.5%), in autumn (27.3%) and in winter (25.7%). The number of
      gangrenous appendicitis is 34.7%-56.7% in boys and 43.5% in girls. The highest
      rate of missed appendicitis is at the age of the highest incidence (15.2%) with a
      peak at the age of 10 years (17.8%) and in January (13.3%). The highest incidence
      of perforated appendicitis is also at the age of the highest incidence (14.9%)
      with the peak at the age of 8 years (15.6%) and in June (13.5%). Perforation is
      more frequent in boys (58.1%) than in girls (49.9%). The number of "negative"
      appendicitis is 15.8%. Prevention of acute appendicitis still remains open due to
      lack of knowledge of its etiopathogenesis.

PMID- 9658957
TI  - [The significance of cytokines in the early diagnosis of postoperative
      intraabdominal sepsis].
AB  - The objective of the investigation was to evaluate the possible use of selected
      cytokines and cytokine receptors in the early diagnosis of postoperative
      intraabdominal sepsis. The investigation was focused on the dynamics of plasma
      levels of tumour necrotizing factor-alfa (TNFalfa), interleukin (IL)-1beta, IL-2,
      IL-6, IL-8, IL-10, soluble receptors IL-2 and IL-6 (sIL-2R and sIL-6R) and the
      receptor antagonist IL-1 (IL-1ra). The investigated parameters were tested on
      model operations (resection of large bowel and resection of pancreas). These two
      groups were compared with values recorded in patients with sepsis and with
      healthy subjects. Based on the assembled results the authors recommend to use for
      postoperative investigations the first 48 hours and to follow up the following
      parameters: IL-6, IL-ra or sIL-2R. During the first 48 hours these indicators
      differentiate sufficiently specifically incipient sepsis from an uncomplicated
      postoperative condition. During the subsequent period, i.e. more than 48 hours
      after surgery, it is useful to include in the examination pattern also some acute
      stage proteins (C reactive protein, alfa1-antitrypsin and haptalobin) which
      differentiate sepsis between the 3rd and 5th day after surgery.

PMID- 9658958
TI  - [Reconstructive surgery of the aortic valve in rheumatic stenoses].
AB  - Recently the number of plastic operations of the cardiac valves is increasing.
      The authors present an account on 10 patients with stenosis of the aortic valve
      where they performed a reconstruction without the necessity of a prosthesis.
      Commissurotomy and rasping can be performed in patients when the basic anatomical
      shape and dimensions of the valve are preserved. None of the patients died, one
      was successfully reoperated on account of aortic insufficiency. The authors
      describe and discuss the tactics and technique of the operation. They discuss the
      possibility of reconstruction of the aortic valve in patients indicated for
      aortocoronary reconstruction where the aortic defect appears to be of minor
      impact.

PMID- 9658959
TI  - [Various technics in the surgical treatment of dissection of the thoracic aorta].
AB  - During 1994-1996 at the Clinic of Cardiovascular and Transplantation Surgery of
      IKEM 17 patients were operated with acute dissection of the thoracic aorta type
      A. Based on the applied surgical tactics the patients were retrospectively
      divided into two groups. The first included 8 patients where surgical
      reconstruction of the ascending aorta was implemented in the standard way, the
      second group comprised 9 patients where the method of deep hypothermia and
      circulatory arrest were used. Three operated patients died, all from the group
      with deep hypothermia. The cause of death was twice multiorgan failure and once
      haemorrhage in a female patient with cardiac tamponade before surgery. The
      authors discuss the advantages and some pitfalls of surgery in deep hypothermia
      and circulatory arrest and maintain that neurological disorders are most serious.
      In the conclusion they draw attention to some possible ways how to improve
      hitherto achieved results. They include e.g. reduction of the time interval
      between the development of symptoms of dissection and surgery, careful checking
      of the cooling and heating when using deep hypothermia, as well as better
      prevention of cerebral embolic attacks.

PMID- 9658960
TI  - [Techniques and tactics in multiorgan harvesting].
AB  - The eighties and nineties are characterized by potent development of
      transplantology. Despite this the number of patients with organ failures waiting
      for a suitable organ is steadily increasing. Due to the permanent shortage of
      donors transplantation surgery tries to implement the maximum possible multiple
      organ collection. In the conclusion the authors emphasize the importance of
      satisfactory cooperation of the anaesthesiologist attending donors and the organ
      collection teams.

PMID- 9658961
TI  - [Modern cardiac anesthesia].
AB  - Contemporary cardioanaesthesia is based on the use of opioid effects, whereby
      their dosage is steadily decreased. This calls for supplementation of anaesthesia
      by further pharmacological preparations which ensure adequate anaesthesia.
      Despite great efforts, neither, substances available at present nor their
      combinations are sufficient to suppress surgical stress completely. The authors
      attempt therefore selective influencing of the sympathetic nerve. In this respect
      preparations which stimulate sympathetic alpha2 receptors seem promising. The
      general trend of contemporary cardioanaesthesia is an effort to reduce the time
      spent by patients in the intensive care unit to a minimum. The motivation are in
      the first place economic reasons.

PMID- 9658962
TI  - [Techniques, tactics and organizational aspects of distant procurement of donor
      hearts for transplantation. Experience at the Department of Cardiovascular and
      Transplantation Surgery of IKEM with 100 distant procurement of donor hearts].
AB  - Transplantation of the heart is currently an accepted therapeutic method. One of
      the factors which have an adverse effect on its availability is shortage of
      suitable donors. Distant procurement of hearts helps to extend the number of
      organs for transplantations. The authors present their experience with distant
      procurement of donor hearts performed during more than three years. They evaluate
      the influence of cold ischaemia time of the cardiac graft on early results of
      cardiac transplantations. In the discussion they try to draw attention to some
      problems associated with this technique for other organ retrieval teams
      participating in multiple organ procurement.

PMID- 9658963
TI  - [Spontaneous dissection of the left main coronary artery. Case report].
AB  - The case report of a 59 years old woman present with spontaneous dissection of
      the left main coronary artery including origins of its major branches is
      described here. The patient had emergency surgery and a triple ACEG was
      performed. The postoperative course was uneventful and a control angiogram proved
      both complete graft patency and absence of previous dissection. Six months
      following surgery the patient is doing well except for a minor effort dyspnea.
      The available literary experience with this rare and potentially fatal coronary
      condition is discussed in comments.

PMID- 9658964
TI  - [Double gallbladder].
AB  - The authors demonstrate on an exceptional case the possibility of laparoscopic
      surgery in a patient with the rare finding of vesica fellea duplex. They also
      draw attention to the algorithm of examination methods and possible errors in
      these exceptional cases.

PMID- 9658965
TI  - [Peripheral revascularization of the lower extremities in patients with critical
      limb ischemia].
AB  - The contemporary clinical approach to treatment of patients with critical limb
      ischaemia is based on the conclusions of the European document adopted in
      Rudeshaim in 1991 (Second European Consensus on Critical Limb Ischaemia). The
      authors describe the comprehensive approach of different disciplines at their
      department as the optimal therapy of this serious vascular disease.

PMID- 9658966
TI  - [Heart interventions in Switzerland 1996].
AB  - For the year 1996, as for the previous 11 years, a survey of cardiac invasive and
      surgical procedures in Switzerland was carried out by a standardised
      questionnaire. At the 25 Swiss centres (10 public non-university, 10 private and
      5 university centres) a total of 12,183 coronary revascularisation procedures
      were performed, 60% by percutaneous transluminal coronary angioplasty (PTCA). Of
      all PTCAs, 88% were single vessel interventions. PTCA for ongoing infarction
      accounted for 6% of all PTCAs. The use of coronary stents has increased to 50% of
      all angioplasties. Other interventions like directional atherectomy and
      rotablations have lost ground (0.4%, 35 cases). Only 22 interventions (0.2%) with
      intracoronary laser devices were recorded. Among the new diagnostic tools, only
      coronary ultrasound (233 cases) and Flowire (147) have been used regularly.
      Percutaneous balloon valvuloplasties (60 cases) and catheter closure of
      congenital shunt defects (42 cases) remained rare. Procedure related mortality
      for PTCA was 0.6%, infarction occurred in 1.0% and emergency coronary artery
      bypass grafting (CABG) became necessary in 0.4%. The total number of CABGs
      (4,463) slightly decreased. Among the 2,677 non-coronary operations, 48% were
      performed for valve disease and 51% for congenital heart disease. Heart
      transplantation was performed in 41 patients (1%). Half of the interventional
      catheter procedures were performed at the 5 university centres whereas the
      majority of CABGs were carried out at private centres. Four centres performed
      diagnostic procedures, exclusively. In-house surgical stand-by for PTCA was
      available in 17 of the 21 interventional centres.

PMID- 9658967
TI  - [Gunshot injuries in the head-neck area--basic principles, diagnosis and
      management].
AB  - Bullet wounds are a rare occurrence during times of peace. Recently, however,
      there has been a general increase in the number and severity of this type of
      trauma in our case load. First, the possible firearms and the individual types of
      ammunition will be discussed. Based on this background, the possible types of
      wounds are presented. Principally, one distinguishes ricocheting shots from
      grazing ones, and those leaving bullets lodged in the body from those with
      perforating wounds. The extent of tissue damage depends on internal lacerations,
      on the compression of the tissue and on the temporary cavitation along the
      projectile path. In contrast to other types of injuries, which are caused by a
      blow or impact to the face or skull, gunshot traumas are characterized by an
      irregular path, as well as, by localized destruction of bones with associated
      effects. In this connection, the severity of the bullet wound also depends upon
      the extent of involvement of the viscerocranium. As causes of gunshot wounds
      during times of peace, suicidal intent, the negligent handling of firearms and
      especially brutal crimes are those which come into consideration first and
      foremost. The diagnostic aspect of firearm wounds, beside anamnesis, comprises
      comprehensive X-ray diagnostics for a complete picture. From the therapeutic
      side, tetanus serum and antibiotics as a prophylactic are recommended initially.
      The operative treatment should take place depending on the injury with the
      removal of a possible projectile. Bullet wounds always require an
      interdisciplinary approach to treatment.

PMID- 9658968
TI  - [Otogenic meningitis].
AB  - We present three patients with otogenic meningitis, whose illness varied in
      extent and clinical course. Meningitis and otitis media are associated in 19-22%
      of all meningitis-patients. Streptococcus pneumoniae is the predominant
      microorganism with hemophilus influenzae being the second most important. We
      discuss the importance and problems of spinal puncture, early CT-scan as well as
      further, more extensive and sophisticated examinations to exclude late
      complications or predisposing factors. We emphasize an early start of antibiotic
      treatment, which should not be delayed for diagnostic reasons. With the
      appearance of highly penicillin-resistant pneumococci antibiotic therapy may
      become more difficult in the future, but for the moment pneumococcal infections
      in Switzerland can initially still be treated with cephalosporins or high dose
      penicillin. The use of steroids, although of unproven efficacy, may be considered
      in some cases. An otolaryngologist should initially be consulted for diagnostic
      reasons as well as for possibly indicated early surgery.

PMID- 9658969
TI  - [Missed somatic diagnoses--inexcusable, missed psychogenic somatic disorders--a
      gentleman's offense].
AB  - Overlooking somatic diagnoses is judged a serious failing, overlooking
      psychogenic somatization a minor mistake. This situation derives from the medical
      theory on which the physician bases his opinions, decisions and treatments. In
      this case, the mechanistic model deriving from the introduction of physics and
      chemistry into medicine in the 18th century. A 19 minute verbatim first interview
      illustrates how the biopsychosocial interview method serves to pinpoint
      psychogenic somatization in a woman who had been unsuccessfully examined and
      treated for four years, bringing the underlying blocked process of grief to light
      and making it the focus of therapy. Savings in time, cost and suffering are
      obvious.

PMID- 9658970
TI  - [Incidence of phlebography proven deep venous thromboses of the leg after knee
      joint arthroscopy].

PMID- 9658971
TI  - [Headache, cough, acute dyspnea and diffuse lung infiltration in a young woman.
      Acute eosinophilic pneumonia].

PMID- 9658972
TI  - [Fibromyalgia (generalized tendomyopathy) expert assessment practice].

PMID- 9658973
TI  - [Erectile dysfunction].

PMID- 9658974
TI  - [Organic basis of erectile impotence--evaluation and treatment possibilities].
AB  - Sexual potency in its entire meaning implies: libido, erection, ejaculation which
      are discussed in view of its incidence or loss. Organic reasons for erectile
      dysfunction prevail at a high rate. These are listed regarding efficient
      diagnosis and the therapeutic measures.

PMID- 9658975
TI  - [Erectile dysfunction: psychological causes, diagnosis and therapy].
AB  - For clinical practice, erectile dysfunction is the most important form of male
      sexual disorders. In the majority of patients causation and course of their
      erectile disorder is determined by a close interplay of somatic and psychosocial
      factors. This psychosomatic interaction has to be taken into account during
      diagnostic assessment and therapy. The old dichotomous concepts (psychogenic
      versus organic) of erectile dysfunction have to be replaced by multidimensional
      models that include dispositonal as well as chronifying factors. The main causes
      of psychogenic erectile disorders can be divided into three groups, each
      belonging to a different phase of time: 1. immediate factors (performance
      anxiety), 2. antecedent life events from recent history, 3. developmental
      vulnerabilities from childhood and adolescence. The most important instrument for
      the psychological evaluation of sexually dysfunctional patients is a
      comprehensive sexual history in which partner related aspects should be
      particularly focused. In treating psychogenic erectile dysfunctions sex therapy
      is a reliable and efficient treatment option with a reasonably good long-term
      prognosis. In future, sex therapy should be combined with somatic treatment
      options to reach a truly integrative approach to this complex disorder.

PMID- 9658976
TI  - [Impotence: evaluation and treatment in general practice--what is reliable?].
AB  - Erectile dysfunction has an incidence of 2-9% and it is seen often in general
      practice. But the more recent treatment methods such as intracavernous drug
      injections and vacuum constriction devices are not known by general practitioners
      and normally used drug treatment has no efficacy. The management of impotence of
      the general practitioner should concentrate upon internistic conditions like
      diabetes, hypertension, hypercholesteremia and different drugs causing impotence.
      The symptomatic treatment of erectile dysfunction has to be done by a specialist,
      who is able to offer all therapeutic options.

PMID- 9658977
TI  - [Measuring nocturnal tumescence--value in diagnosis of impotence].
AB  - Nocturnal penile tumescence monitoring (NPT) is a non-invasive method to
      differentiate between organic and psychogenic impotence. The routine use of NPT
      monitoring in the evaluation of impotence is not effective due to its moderate
      sensitivity and specificity with small therapeutic benefit and relatively high
      costs. Patient's selection by intracavernous pharmacotest can improve the
      efficiency of the investigation, so the method can help to secure the diagnosis
      of a psychogenic impotence and then take effect on adequate therapy.

PMID- 9658978
TI  - [Ambulatory treatment of erectile dysfunction].
AB  - Intracavernous injection of vasodilating agents and vacuum constriction devices
      are the therapeutic alternatives in outpatients with secondary erectile
      dysfunction in Europe. The agents commonly used include papaverine, alprostadil
      and phentolamine, singly or in combination. Quality of erectile response has
      agent related characteristics and is dose-dependent. Optimal clinical response
      ranges from full response for adequate sexual performance to a duration exceeding
      patient's and partner's wishes. Therefore, the adequate response must be titrated
      for every patient individually. Vacuum erection devices are efficacious and well
      accepted from patients and their partners if they can accept the artificial
      aspect of this approach. Vacuum erection devices are not suitable for men in
      unstable relations. Injection therapy and vacuum device interfere with
      spontaneity. The medicated urethral system for erection (MUSE) is a new approach
      to deliver alprostadil to the corpus cavernosum. The application is more user
      friendly than with injections but response rates for adequate satisfactory sexual
      performance are lower than with intracavernous injections. Therefore indications
      may be limited to specific etiologies such as neurogenic erectile dysfunction.
      There is currently no efficient pill on the market although a wide range of
      therapies are used. Approval and introduction of new oral treatments like
      Sildenafil and others are awaited by patients and physicians. The availability of
      new and highly efficient treatment options does not simplify evaluation and
      treatment of patients with ED. In the contrary they request refinements in the
      diagnostic process for etiologic diagnosis with subsequently least invasive
      treatment and minimal side effects.

PMID- 9658979
TI  - [Testosterone and impotence--when is androgen substitution advisable?].
AB  - Testosterone and dihydrotestosterone play a critical role during embryogenesis of
      the male genitalia. The development of secondary sex characteristics depends on
      normal circulating androgen levels. They maintain libido and sexual potency.
      Before testosterone supplementation men with erectile failure should receive
      through hormonal investigation. Testosterone is useless in the treatment of
      erectile problems in men with normal androgen levels. Testosterone can be
      administered by intramuscular, oral or transdermal routes. Transdermal systems
      produce serum testosterone levels closely mimicking the diurnal pattern described
      in healthy young men. In elderly men during long term therapy, prostate specific
      antigen should be measured regularly to anticipate malignant growth in the
      prostate.

PMID- 9658980
TI  - [Priapism].
AB  - Priapism is the persistence of an erection that does not result from sexual
      desire. Diagnosis is based on history, clinical examination, diagnostic
      aspiration of blood and measurement of blood gas levels. The purpose of treatment
      is to increase corporeal outflow by aspiration and injection of alpha stimulating
      agents. In some rare cases selective angiographic embolisation or surgical
      resection of a bleeding intracavernous artery is required. Prognosis is good if
      diagnosis and treatment are not delayed.

PMID- 9658981
TI  - [Induratio penis plastica].
AB  - The symptoms of Peyronie's disease consist of fibrotic plaque formation, penile
      deviation and painful erection. The etiology is still unknown. During its
      progress the disease can cause erectile failure. The plaques mainly involve the
      dorsal tunica of the penis. The diagnosis is made by palpation of the penis. The
      ultrasound examination evaluates the plaque localization and possible
      calcifications. Autophotography of penile deviation and duplex sonography of the
      cavernous arteries used to measure arterial blood flow complete the diagnostic
      efforts. Spontaneous remissions occur as well as chronic courses. Oral medication
      is the first step in therapy. In cases with severe penile deviation leading to
      disability to perform intercourse, persisting pain or erectile failure operative
      management is indicated. Plaque surgery, modified corporal plication or
      implantation of a penile prosthesis must be evaluated individually.

PMID- 9658982
TI  - [New principle in therapy of erectile dysfunction: sildenafil].
AB  - Erectile dysfunction may have psychological as well as a variety of organic
      causes. This necessitates in each case a careful medical evaluation. Various
      commonly used drugs, as well as alcohol and narcotics, may interfere with
      erection and should, whenever possible, be discontinued before starting
      treatment. Organic diseases should be identified and, if feasible, specially
      treated. In the remaining majority of afflicted men, psychological treatment and
      partner counseling may produce an improvement, but ultimately what is necessary
      remains an effective and safe medication. The drug, Sildenafil, introduces a new
      therapeutic principle. During sexual nerve stimulation, nitric oxide (NO) is
      released from nerves into the cells of the penile erectile bodies. NO activates
      in turn its "second messenger", the substance cyclic GMP, and the latter induces
      the vasorelaxation and blood filling of the erectile bodies. Orally administered
      Sildenafil competitively inhibits phosphodiesterase type 5, which physiologically
      inactivates cyclic GMP in the erectile bodies. Thus, Sildenafil increases in men
      with erectile dysfunction the NO-stimulated cyclic GMP concentration and,
      thereby, improves erection. This new therapy is attractive because 1. Sildenafil
      is the first pill (for oral use) with established efficacy that benefits most men
      with insufficient erection; 2. compared with previous therapeutic approaches
      (such as drug injections in the penis, instillations into the urinary duct,
      vacuum pumps or even prostheses), Sildenafil is at least as effective, is easy to
      take and appears well tolerated with no risk of a prolonged erection; 3.
      remarkably, this medication stimulates erection only during sexual arousal and,
      thus, has a rather "natural" effect, and 4. side effects (including headache,
      facial flushing and dyspepsia or epigastric discomfort) were mostly of mild
      degree and transient, so that only 4% of men interrupted treatment for this
      reason. Sildenafil does not need to be taken daily, but may be taken, when
      needed, 1 hour before a planned sexual activity. The new pill has the potential
      to enliven the boys "wunder horn" with fresh sound.

PMID- 9658983
TI  - Surgical sterilization in the United States: prevalence and characteristics, 1965
      95.
AB  - OBJECTIVES: This report presents national data on the prevalence of surgical
      sterilization from 1965 to 1995 among women 15-44 years of age. Data are shown by
      type of sterilizing operation and demographic characteristics of the women. For
      the 1995 survey data, reasons for the three most common sterilizing operations
      (tubal ligation, vasectomy, and hysterectomy) are shown, as well as the desire
      for reversal among those with potentially reversible operations. METHODS: Data
      are based on nationally representative samples of women 15-44 years of age: the
      1965 National Fertility Study (NFS), and the 1973, 1982, 1988, and 1995 cycles of
      the National Survey of Family Growth (NSFG). RESULTS: After rising from 16 to 42
      percent between 1965 and 1988, the prevalence of surgical sterilization among
      married women 15-44 years old remained stable at 41 percent in 1995. Age, parity,
      religious affiliation, and education continued to be strongly associated with
      overall surgical sterilization levels. Tubal ligation and vasectomy were equally
      prevalent in the 1965 and 1973 surveys, but since 1962, tubal ligation has been
      more prevalent than vasectomy. CONCLUSIONS: Several factors contributed to the
      rise in reliance upon surgical sterilization among women 15-44 years old over the
      last 3 decades: (a) aging of the post-World War II Baby Boom women (and their
      partners) through the primary reproductive years; (b) relatively high
      contraceptive failure rates, particularly among socioeconomically less advantaged
      women; and (c) higher expectations for contraceptive effectiveness, safety, and
      convenience. Overall sterilization prevalence may be leveling off among women 15
      44 years old, in part due to greater delay of first and subsequent births, thus
      making sterilization less of a concern while women are in this age range.

PMID- 9658984
TI  - [Theophylline in treatment of bronchial obstructive diseases].
AB  - The article is the review of the data from literature concerning the new role of
      theophilline in the management of asthma and chronic bronchoobturative pulmonary
      disease. Theophilline has been widely used to treat asthma and COPD patients
      worldwide and is classified as a bronchodilatator, although there is increasing
      evidence that it has antiinflammatory activity and enhances immunomodulatory
      effects. The latter is therapeutically relevant to markedly lower serum
      concentration (even < 10 micrograms/ml) than this required for bronchodilatation.
      That is particularly clinically important because significant adverse effects
      have been seen only in the case of doses greater than 10 micrograms/ml.

PMID- 9658985
TI  - [Acute and critical leg ischemia].

PMID- 9658986
TI  - [Comparison of anxiety in patients before surgery for varicose veins and
      laparoscopic cholecystectomy].
AB  - The trial of estimation of the fear degree before operation and its dependence on
      the patient's sex, type of operation and anaesthesia was performed. 76 patients
      before the operation were examined: group I--38 patients, including 27 women and
      11 men waiting for the repair of lower extremities varicose veins under local
      anaesthesia, and group II--also 38 patients, including 27 women and 11 men before
      the laparoscopic cholecystectomy due to cholecystolithiasis. The Polish version
      of the Spilberg's State--Trait Anxiety Inventory was used in the estimation of
      the fear. The statistically significant difference of the preoperative fear
      degree between examined groups was not found. There were also no significant
      differences between men and women in the same group. Women in both groups
      displayed a significantly higher values of the fear as a trait. Probably
      laparoscopic operations are considered by the patients as more safe than
      traditional ones, and maybe the trust in doctors causes the fact that the
      operation under general anaesthesia is connected with low fear as well as the
      operation under local anaesthesia.

PMID- 9658987
TI  - [Usefulness of biochemical tumor markers (CEA, Ca 19-9, ferritin and sialic acid)
      in diagnosis and prognosis of colonic neoplasms].
AB  - The aim of the study was: to determine the value of CEA, Ca 19-9, ferritin and
      sialic acid in diagnostics, to assess the prognostic role of serum CEA and Ca 19
      9 levels before surgery and to evaluate their usefulness in diagnostics of
      recurrences. The study included 352 patients with colorectal carcinoma
      (adenocarcinoma). The preoperative level of CEA was elevated in 286 patients, Ca
      19-9 in 108, ferritin in 60 and sialic acid in 58 patients. All of them are poor
      markers in diagnostics because of the low sensitivity, respectively 47.6%, 37.0%,
      16.7% and 55.2%. Preoperative high, CEA and Ca 19-9 values are associated with a
      significantly poorer prognosis and with frequency of recurrences.

PMID- 9658988
TI  - [Neoplasms of the large intestine in elderly patients].
AB  - The aim of the study was to compare 2 groups of patients with colorectal cancer
      treated between 1985-1995. The analysed group consisted of 228 patients aged over
      70. Reference group consisted of 330 younger ones. The stage of colorectal cancer
      (Dukes classification) was similar in both groups. Complications of the
      colorectal cancer often occurred in the elderly patients (21.9% vs. 10%,
      respectively). The incidence of associated diseases was also higher (70.6% vs.
      59.1%). Operability was similar in both groups (93% vs. 98.8%) but resectability
      was lower in the elderly group (67.4% vs. 80.1%, respectively). Postoperative
      complications were observed in the similar percent of cases except those aged
      over 70 (17.5% vs. 4.9%), especially after emergency operations (31.6% vs. 4.7%,
      respectively).

PMID- 9658989
TI  - [Levels of malonyl dialdehyde and vitamin A in blood serum after administration
      of therapeutic doses of nifedipine].

PMID- 9658990
TI  - [Concentration of copper and ceruloplasmin in serum of patients treated for
      epilepsy].
AB  - In 54 epileptic patients (28 females and 26 males) aged 21-48, serum copper (Cu)
      and ceruloplasmin (Crl) concentrations were assessed. Comparing with control
      group mean serum Cu and Crl concentrations were significantly increased. We
      suspect that antiepileptic drugs may influence the serum Cu and Crl
      concentrations by hepatic enzymes induction. Clinical picture of epilepsy and
      treatment duration does not influence serum Cu and Crl concentrations.

PMID- 9658991
TI  - [A proposal for management of severe acute bronchial asthma].
AB  - The term acute severe asthma has recently replaced status asthmaticus to describe
      severe asthma attack. Perhaps, this change was associated with better asthma
      treatment, which prevents currently patients from occurrence of such a severe
      exacerbation of this disease, to call it status asthmaticus. "Global Initiative
      for Asthma Global strategy for asthma management and prevention" contains
      rational guidance on management of this disease, but provide little information
      about status asthmaticus. This fact was the main reason to prepare present
      proposal, which was based on suggestion of Global Initiative for Asthma, other
      current scientific papers and our own experience. We hope that this proposal will
      begin further discussion, which will bring us closer to more rational solution of
      this problem.

PMID- 9658992
TI  - [Sleep apnea syndrome in patients with diabetes. Effectiveness of treatment for
      respiratory assistance at night with continuous positive airway pressure].
AB  - The group of 30 patients with OSA and diabetes type I or II has been examined.
      After the first test with MESAM 4, 5 patients with considerable nocturnal
      desaturation and heart rate disorders during sleep have been found. All diabetes
      type II. Two polisomnographic studies (the first diagnostic polisomnography and
      the second study for the settlement of treatment with CPAP) have been performed
      in the patients. After 6 months of applying CPAP all the patients have been
      examined again. The apnoea index was decreased (from 87.5 to 11.2) and a better
      control of both systemic arterial pressure and glycaemia, saturation > 80% has
      been obtained.

PMID- 9658993
TI  - [Iatrogenic causes of post-traumatic reflex sympathetic dystrophy].
AB  - It is suspected that some faults in the course of the treatment of traumas such
      as: reduction of fractures without sufficient anaesthesia, repeated reductions,
      tightness of casts, immobilization of fingers, ignoring patients' complaints of
      the pain and swelling about or painful rehabilitation may have effect on the
      development of the post-traumatic reflex sympathetic dystrophy. These opinions
      have not been confirmed by clinical trials. The incidence of above mentioned
      factors was analysed retrospectively in 165 patients with post-traumatic reflex
      sympathetic dystrophy within upper extremity and in 86 patients following
      fracture of distal radius without features of the condition (control group). It
      was found that the patients with reflex sympathetic dystrophy significantly more
      frequently complained of pain and swelling in the course of the treatment of
      trauma in the cast and they were subjected more frequently to painful
      rehabilitation after removing the cast. These factors appeared to have an effect
      on developing the reflex sympathetic dystrophy (comparing with the control
      group). The role of remaining factors that are often considered as significant in
      the development of reflex sympathetic dystrophy--painful and repeated reductions
      of fractures as well as immobilization of fingers-was not confirmed.

PMID- 9658994
TI  - [Prostanoids in treatment of liver diseases].
AB  - Knowledge related to the role of prostanoids (which include prostaglandins and
      prostacycline) in controlling biological phenomena in particular organs, as well
      as, in the whole human body, has increased gradually since the year 1930, up to
      now. However the role of these substances in liver functions has been developed
      quite recently. Experimental and clinical researches on hepatoprotective activity
      of prostanoids have been carried out in the last years. Mechanism of their action
      remains still unclear and can result from induction of hepatocytes regeneration,
      hepatocytes membranes stabilization, improvement of hepatic microcirculation,
      intracellular metabolism and respiration. In chronic liver damage it can be
      related to inhibition of fibrosis. These experimental observations correlate with
      amelioration of severe viral hepatic injury and improved prognosis after liver
      transplantation.

PMID- 9658995
TI  - [Lipoid pneumonia].
AB  - The authors describe in the article etiology, histopathological features,
      clinical picture and diagnostics of endogenous and exogenous lipoid pneumonia.
      The advantages of broncho-alveolar fluid examination and computed tomography in
      the diagnostics were emphasized.

PMID- 9658996
TI  - [Chronic pleural effusion from the pancreas].
AB  - Chronic, pleural effusion, characterized by a very high pancreatic enzymes
      activity is a rare complication of the pancreatic diseases. It is pathognomonic
      for the pancreaticopleural fistula, arising most frequently in the patients with
      chronic, alcoholic pancreatitis. Clinical manifestations of the chronic pleural
      effusion lead the physician's attention to the pulmonary diseases, what often is
      the cause of misdiagnosis. The diagnostics of this pancreatic diseases
      complication bases on the effusion's pancreatic enzymes activity evaluation and
      visual methods such as computed tomography, ultrasonography, endoscopic
      retrograde cholangiopancreatography. Management can be started conservatively,
      but if the result is not adequate, surgical treatment is needed. As the cases of
      pancreatic, chronic pleural effusion may be commoner than it is reported, author
      postulates a routine evaluation of the pleural effusion alpha-amylase activity in
      each case of the unclear pleural effusion.

PMID- 9658997
TI  - [The significance of viral infection in asthma].
AB  - The aim of the paper was to systematize, according to recent literature data, the
      processes taking place in respiratory tract in the course of viral infections and
      to emphasize their relevance to the development of bronchial hyperreactivity and
      the pathogenesis of asthma. Furthermore, the pathophysiological mechanisms which
      may be responsible for chronic infection and successively for nonspecific
      bronchial hyperresponsiveness were reported. Viral pathogens which are suggested
      to initiate bronchial asthma, its exacerbations and induce dyspnoea were
      mentioned.

PMID- 9658998
TI  - [Clinical aspects of chlamydia respiratory tract infections and their role in the
      pathogenesis of asthma].
AB  - Recent world-wide publications were reviewed in order to determine the clinical
      characteristics and therapeutic relevance of the chlamydial respiratory tract
      infections in humans. It was emphasized that Chlamydia pneumoniae could initiate
      asthma and may be associated with acute asthma exacerbation. Laboratory
      procedures for identifying chlamydia and difficulties concerned with the
      diagnostics of this intracellular pathogen were also presented. In patients with
      evidence of chlamydial infection the casual treatment (macrolides, tetracyclines,
      fluoroquinolones) may induce major improvement or complete resolution of asthma.

PMID- 9658999
TI  - [The ability of drivers to give first aid--testing by questionnaire].
AB  - Road accidents have become a serious social problem. The scale and complexity of
      this problem shows clearly that there is a necessity to improve citizens' ability
      to give first aid which is especially essential in the case of drivers. Thus
      special training how to give first aid at the accident place seems to be of the
      primary importance. The objective of this paper is to: 1) identify to what extent
      the drivers of motor vehicles are prepared to provide first aid for casualties of
      the road accidents, 2) evaluate the training system of teaching motorists how to
      give first aid before professional help arrives, 3) identify drivers' views on
      possibilities of decreasing the number of fatal casualties of the road accidents.
      The questionnaire was given to 560 employees of local government institutions in
      the city of Lublin either professional or non-professional drivers. The direct
      method and anonymous questionnaire were used. The results of the questionnaire
      revealed clearly that very few drivers are well-prepared to give proper first aid
      at the accident site. No matter what sex, education or driving experience, the
      drivers have not got enough skills to give first aid and the effect is enhanced
      by various psychological barriers. The questioned drivers shared the opinion that
      first aid training is badly run. The drivers stressed bad quality of the training
      and the fact that it is impossible to acquire practical skills that may be
      required in the case of emergency. Drivers' views on possibilities of decreasing
      the number of fatal casualties of the road accidents included, among others, the
      following propositions: in addition to the driving licence exam first aid exam
      should be compulsory severe enforcement and execution of the law which regulates
      the mandatory first aid giving.

PMID- 9659000
TI  - Patient participation in treatment decision making and the psychological
      consequences of breast cancer surgery.
AB  - Women in the early stages of breast cancer can be treated effectively with either
      modified radical mastectomy or tumor excision plus postoperative radiation
      therapy. Thus, breast cancer patients may be given a choice between these two
      modes of treatment. In some states, physician disclosure of such treatment
      alternatives for breast cancer is mandated by law. Despite the belief that
      patient participation in decision making is beneficial, the evidence is
      preliminary, although generally supportive. This study examined the extent to
      which patient participation in the choice of surgical options was related to
      psychological functioning, fear of cancer recurrence, and aspects of treatment
      satisfaction 3 and 13 months postoperatively. Few associations with degree of
      participation in treatment decision making or type of surgical treatment emerged
      after 3 months. After 13 months, however, women with greater levels of input into
      their treatment plan were more satisfied with their medical care, although they
      were not better off in terms of psychological functioning or fear of cancer
      recurrence. The positive effects of shared treatment decision making may be more
      closely related to aspects of longer term treatment satisfaction rather than a
      buffer against psychological distress resulting from breast cancer.

PMID- 9659001
TI  - "What the 'caine was tellin' me to do." Crack users' risk of HIV: an exploratory
      study of female inmates.
AB  - This study describes factors that place crack-addicted female jail inmates at
      risk for HIV infection. The study provides a portrait of the spheres of
      influences that directly and indirectly promote HIV risk-taking behaviors,
      women's efforts toward protecting themselves, and reported sexual behaviors. The
      study documents the far-reaching effects of crack addiction. One-and-a-half-hour
      interviews were conducted with 14 inmates recovering from crack addiction. The
      women were aged 19 to 39, and 13 were African American. The results of this study
      suggest that women's addictions are greatly shaped by their family and intimate
      relationships. Addictive behavior often precluded safer sex behaviors and
      increased a woman's likelihood of engagement in HIV-risky behaviors. Many women
      were victims of childhood and adulthood sexual and physical victimization. Women
      sought to protect themselves through sexual self-protection strategies, although
      these measures were often not effective HIV risk-reduction strategies.

PMID- 9659002
TI  - Behavioral and psychosocial consequences of HIV antibody counseling and testing
      with African American women.
AB  - This study compared a sample of low-income African American women in the
      southeastern United States who had and had not yet undergone HIV counseling and
      testing on risk-related cognitive mediating variables and self-reported sexual
      behaviors. Four hundred sixty (N = 460) African American women were recruited
      from health clinics and community settings in a southern city. Forty-five percent
      of the women (n = 207) had undergone HIV counseling and testing, whereas 55% (n =
      253) had never been tested. Women who were seropositive were excluded from the
      analyses. After providing informed consent, the women completed a battery of
      cognitive mediating measures assessing AIDS knowledge, attitudes theoretically
      relevant to risk reduction, and self-reported sexual behavior. In addition, each
      participant demonstrated condom application skills using a penile model. Women
      who had undergone testing were younger, rated HIV disease as more serious,
      considered AIDS a greater health concern, had more positive attitudes toward HIV
      prevention, expressed greater intentions to use condoms, and evidenced a greater
      commitment to self-protective behavior than women who were not yet tested. Women
      who had undergone HIV antibody testing, however, showed no differences in sexual
      behavior from women who were never tested. Sexual behavior, including numbers of
      partners, frequency of unprotected intercourse, and inconsistent condom use, left
      women in both groups at significant and comparable risk for HIV and sexually
      transmitted disease infection. HIV counseling and testing alone may not be
      effective primary prevention strategies for promoting risk reduction among
      African American women.

PMID- 9659003
TI  - Cervical cancer and STD health beliefs: predicting pelvic exam intentions in
      undergraduates.
AB  - We surveyed 119 female undergraduates to investigate if the health belief model
      for both cervical cancer and sexually transmitted diseases (STDs) would predict
      pelvic examination intentions. Results for cervical cancer and STDs were similar,
      with barriers to obtaining an exam and perceived susceptibility contributing most
      consistently to intentions. Respondents rated themselves as more susceptible to
      cervical cancer than to STDs and rated STDs more serious than cancer.
      Discriminant analysis found sexual activity, barriers, susceptibility to STDs,
      benefits of a pelvic exam for cervical cancer, and age to reliably distinguish
      women who had gotten a pelvic exam from those who had not. Contrary to previous
      research, physique anxiety was a positive predictor of intentions when health
      beliefs were controlled, suggesting it may represent generalized body anxiety for
      some women.

PMID- 9659004
TI  - Training in diagnostic ultrasound: essentials, principles and standards. Report
      of a WHO Study Group.
AB  - Diagnostic ultrasound is a rapidly developing imaging technology widely used in
      both industrialized and developing countries. For certain diagnostic
      applications, ultrasound has replaced commonly used radiographic imaging
      techniques as the method of choice, and it has also made possible new areas of
      diagnostic investigation. Moreover, equipment for ultrasound imaging tends to be
      cheaper and more widely available than imaging equipment requiring the use of
      ionizing radiation. This combination of factors has resulted in the proliferation
      of diagnostic ultrasound units, and in some cases their use by individuals
      without proper training, or under conditions of inadequate control. This report,
      the outcome of a recent WHO Study Group, is concerned with the essentials,
      principles, and standards of training for this important technology. The Study
      Group has analysed problems in the effective use of diagnostic ultrasound and
      reviewed current training practice worldwide. For the first time, outlines of
      recommended training curricula for the general, advanced, and specialized use of
      diagnostic ultrasound are presented. Recommended standards for training
      programmes, training centres, and the training process are also discussed. The
      report highlights the role played by professional societies, but also calls
      attention to the need for appropriate legislation and regulation. The Study
      Group's recommendations are relevant to all those involved in the use of
      diagnostic ultrasound technology, even in countries where existing standards of
      practice are high. In addition to ultrasound specialists, the report should be of
      particular interest to those responsible for medical education or for formulating
      policies regarding the use of health technology.

PMID- 9659005
TI  - [Psychophysiologic reactions to predictable aversive stimuli in a delayed
      conditioning paradigm: reinstatement of the orientating reaction or informational
      control?].
AB  - The preception and orienting response (OR) reinstatement hypotheses are
      alternative explanations for the reduced responding to predictable as compared to
      unpredictable aversive stimuli. To test differential predictions from both
      theories, 60 subjects were presented with 30 stimuli varying in intensity (60
      dB(A) vs 100 dB(A)) and predictability (constant vs variable warning) in a 2 x 2
      between subject design. Impact ratings, SCR and heart rate were recorded as
      dependent variables. According to the preception hypothesis a steep and early
      decrease of responding in the predictable 100 dB(A) condition was expected,
      whereas according to the OR reinstatement hypothesis a slower decrease with
      differences between the predictable and unpredictable stimuli at both intensities
      was hypothesized. To control for response interference only those trials were
      selected for the analysis for which the interval was the same in the variable and
      constant warning condition. Results revealed an intensity effect for the SCRs and
      impact ratings, but no effect of predictability. Although for the heart rate
      magnitude the intensity by predictability was found in favor of preception, this
      result appeared to be due to differences in sensitivity between groups during the
      warning interval. It was concluded that neither hypothesis proved to provide a
      valid account for the reduced responding to predictable aversive stimuli, but
      that the data seemed to be most consistent with a safety signal interpretation.
      Time estimation was considered to be a crucial variable. It is suggested that
      beyond mere signalling, additional beneficial effects of predictability can be
      demonstrated in studies where procedures are used which make time estimation
      unnecessary.

PMID- 9659006
TI  - [Negative priming designs: comparison and improvement of measurements for
      detection of cognitive inhibition].
AB  - Ignoring a distractor on a prime trial generally impairs responses to that
      stimulus on a subsequent probe trial. This so called negative-priming (NP) effect
      supports the view that the representations of distracting stimuli underly a
      cognitive inhibition during target selection (Tipper, 1985). Aiming at the
      optimization of NP designs for analyzing cognitive inhibition the present paper
      investigates two open questions within this context: Which classical designs
      using words, letters, or pictures as stimuli are most accepted by subjects and at
      the same time result in possibly strong NP effects? What is the time course of
      NP, and at which interstimulus interval (ISI) the maximum is reached? In
      experiment 1, three "classical" NP designs were compared within one sample of
      subjects and a picture design was selected as the most suitable one. In
      experiment 2 the ISI was varied within subjects; the maximal NP effect was found
      at an ISI of around 1000 ms.

PMID- 9659007
TI  - [Preliminary experiments on the correlation of speech errors and working memory].
AB  - This article is based on the conjecture that a relation exists between the
      phonological loop, part of the working memory (Baddeley, 1997), and speech
      production. The influence of verbal material stored in the phonological loop on
      the frequency of slips during articulation was studied experimentally. The SLIP
      technique of inducing speech errors was used (Baars, 1992). Pairs of words are
      presented successively to the subjects for one second each. Some of the word
      pairs are to be spoken aloud. The articulation of these words can be influenced
      by preceding phonologically interfering words in such a way that the probability
      of exchanging the first phonemes of both words is increased (spoonerisms). In
      both exploratory experiments we performed, the time interval between the
      phonologically interfering information and the pairs of words which had to be
      spoken aloud was systematically manipulated. According to Baddeley's theory of
      working memory (1997) it was expected that phonological interference should be
      restricted to a time interval of about two seconds. This expectation was
      supported empirically.

PMID- 9659008
TI  - Limiting models for calcification in fibrous tissues adjacent to orthopedic
      implants: variational indicator functions and influences of implant stiffness.
AB  - Calcification and eventual integration of orthopedic implants into bone is
      important to many load-bearing devices, and the influence of load and implant
      stiffness on this process are assessed in this mathematical modelling study.
      Three research questions are posed in this study. First, can limiting material
      models provide useful information on the overall behavior of the tissue adjacent
      to a loaded orthopedic implant? Second, can the limiting models lead to
      optimization criteria? Third, can an optimization approach be used to
      differentiate between the four prospective remodeling rate equations which are
      proposed? The answers are yes, yes, and no, respectively. A two degree of freedom
      lumped parameter model for axial loading of an intramedullary implant is
      considered. Two limiting composite material models are used, and the strain
      energy density in the calcified and non-calcified phases are assessed as stimuli
      for calcification. The rate equations posed here assume that the calcified
      material volume fraction decreases at high strain-energy densities, and increases
      at small strain-energy densities. In all four cases (both models, both phases)
      the steady states for these rate equations find equilibrium points of indicator
      functions which are a weighted sum of total strain energy and the mass of
      calcified tissue in the layer considered. The weights on strain-energy density
      and mass differ in each case. This shows that for appropriate choices of
      parameters, all four models can yield the same results, and it also shows that an
      optimization approach does not uniquely determine the appropriate rate equation
      in these cases. The rate equations showed complicated dynamic behavior and a
      phase-plane analysis was used which led to upper bounds on load, which depended
      on implant stiffness and distal support. The predictions of the four cases
      studied are compared.

PMID- 9659009
TI  - Using lazy evaluation to simulate realistic-size repertoires in models of the
      immune system.
AB  - We describe a method of implementing efficient computer simulations of immune
      systems that have a large number of unique B- and/or T-cell clones. The method
      uses an implementation technique called lazy evaluation to create the illusion
      that all clones are being simulated, while only actually simulating a much
      smaller number of clones that can respond to the antigens in the simulation. The
      method is effective because only 0.001-0.01% of clones can typically be
      stimulated by an antigen, and because many simulations involve only a small
      number of distinct antigens. A lazy simulation of a realistic number of clones
      and 10 distinct antigens is 1000 times faster and 10,000 times smaller than a
      conventional simulation--making simulations of immune systems with realistic-size
      repertoires computationally tractable.

PMID- 9659010
TI  - Emergence of rules in cell society: differentiation, hierarchy, and stability.
AB  - A dynamic model for cell differentiation, where cells with internal chemical
      reaction dynamics interact with each other and replicate was studied. It led to
      spontaneous differentiation of cells and determination, as discussed in the
      isologous diversification. The following features of the differentiation were
      obtained: (1) hierarchical differentiation from a 'stem' cell to other cell
      types, with the emergence of the interaction-dependent rules for differentiation;
      (2) global stability of an ensemble of cells consisting of several cell types,
      that were sustained by the emergent, autonomous control on the rate of
      differentiation; (3) existence of several cell colonies with different cell-type
      distributions. The results provide a novel viewpoint on the origin of a complex
      cell society, while relevance to some biological problems, especially to the
      hemopoietic system, is also discussed.

PMID- 9659011
TI  - Evidence-based intensive care medicine.

PMID- 9659012
TI  - Ethics and research in anaesthesia.

PMID- 9659013
TI  - The effect of education, assessment and a standardised prescription on
      postoperative pain management. The value of clinical audit in the establishment
      of acute pain services.
AB  - A study involving 2738 patients in 15 hospitals in the United Kingdom was
      undertaken to evaluate the effect of simple methods of pain assessment and
      management on postoperative pain. The study consisted of four parts: a survey of
      current practice in each hospital; a programme of education for staff and
      patients regarding pain and its management; the introduction of formal assessment
      and recording of pain and the use of a simple algorithm to allow more flexible,
      yet safe, provision of intermittent intramuscular opioid analgesia; and a repeat
      survey of practice. One hospital from each of the former health regions of
      England and Wales was selected for inclusion in the project. Hospitals included
      representatives of different size units (university, large and small district
      general hospitals). As a result of the study, there was an overall reduction in
      the percentage of patients who experienced moderate to severe pain at rest from
      32% to 12%. The incidence of severe pain on movement decreased from 37% to 13%
      and moderate to severe pain on deep inspiration from 41% to 22%. Similar
      decreases were seen in the incidence of nausea and vomiting. There was also a
      slight reduction in the incidence of postoperative complications. This study
      shows that simple techniques for the management of postoperative pain are
      effective in reducing the incidence of pain both at rest and during movement and
      should form part of any acute pain management strategy.

PMID- 9659014
TI  - The effect of increasing degrees of spinal flexion on cerebrospinal fluid
      pressure.
AB  - The effects of increasing degrees of flexion on cerebrospinal fluid pressure were
      investigated in 12 neurosurgical patients requiring lumbar subarachnoid drains.
      Cerebrospinal fluid pressure and central venous pressure were measured in three
      positions: fully flexed ('chin on chest'), flexed at ninety degrees and straight.
      There was a significant increase in cerebrospinal fluid pressure on moving from
      the fully flexed to the flexed position (p < 0.0001), but not from the flexed to
      the straight position. These results were mirrored by smaller changes in central
      venous pressure. In patients without intracranial pathology these increases in
      cerebrospinal fluid pressure are probably unimportant. However, intracranial
      pathology may result in low cerebral perfusion pressures and any increase in
      cerebrospinal fluid pressure in this group may be harmful. The fully flexed
      position should be avoided when inserting lumbar drains in at risk patients.

PMID- 9659015
TI  - Anaesthesia and the QT interval. Effects of isoflurane and halothane in
      unpremedicated children.
AB  - The effects of isoflurane and halothane on the QT interval were investigated
      during induction of anaesthesia. Fifty-one unpremedicated, ASA grade 1 children
      were studied. Anaesthesia was induced with either isoflurane (n = 25) or
      halothane (n = 26) and was maintained to the end of the study with end-tidal
      concentrations of between 2.5% and 3%. Recording of the electrocardiograph, heart
      rate and systolic arterial pressure were obtained at the following times: before
      induction of anaesthesia; 1 min and 3 min after stable end-tidal concentrations
      of anaesthetic agent had been reached; 1 min and 3 min following vecuronium
      administration; at the time of tracheal intubation and 1 min and 3 min later.
      Isoflurane significantly prolonged the QT interval (p < 0.001), in contrast to
      halothane which shortened it (p < 0.01). Heart rate remained largely unchanged
      during isoflurane anaesthesia but it decreased in the presence of halothane (p <
      0.001). In both groups, systolic arterial pressure decreased significantly after
      induction of anaesthesia (p < 0.001) and remained so to the end of the study. In
      the isoflurane group, 12 children developed ECG repolarisation abnormalities and
      in one child an arrhythmia was noticed. In the halothane group, one child
      developed repolarisation changes while arrhythmias were observed in 10 children.
      There were no adverse sequelae. It is concluded that halothane may be a better
      anaesthetic agent than isoflurane for use in children with a prolonged QT
      interval.

PMID- 9659016
TI  - Anaesthetic induction time for tracheal intubation using sevoflurane or halothane
      in children.
AB  - The current study was designed to determine the anaesthetic induction time
      required for tracheal intubation (TimeEI) with equipotent inspired concentrations
      of 5% sevoflurane and 2.5% halothane in oxygen. TimeEI that prevents 50% and 95%
      of patients from coughing and gross purposeful muscular movements after
      intubation was defined as TimeEI50 and TimeEI95, respectively. Thirty-six
      patients aged 1-7 years were enrolled in the study. Anaesthesia was induced via
      mask and when TimeEI attained a predetermined value, intubation was performed
      using an uncuffed tube. Each TimeEI at which tracheal intubation was attempted
      was predetermined according to the up-and-down method. When intubation was
      accomplished without gross purposeful muscular movements, it was considered a
      smooth intubation. Determination with this method revealed that TimeEI50 and
      TimeEI95 for the sevoflurane/halothane groups were 147/214 s and 194/255 s,
      respectively. In conclusion, it is possible to determine TimeEI using an inspired
      sevoflurane concentration of 5% and halothane 2.5% in oxygen. The technique with
      5% sevoflurane seems more practical for paediatric anaesthesia induction in busy
      clinical situations.

PMID- 9659018
TI  - Performance characteristics of a 'to and fro' disposable soda lime canister.
AB  - The performance of the Intersurgical disposable soda lime canister was compared
      to British Pharmacopoeia standards for carbon dioxide absorption and to other
      carbon dioxide absorber systems. This canister system more than adequately
      fulfilled the equivalent of the British Pharmacopoeia standard for CO2
      absorption. It performed efficiently for over 3 h of continuous use, absorbing
      200 ml.min-1 at varying combinations of tidal volume and ventilation rate.
      Efficiency was not dependent on close matching of tidal volume with canister
      volume and there was no channelling of gases. Heat was generated by the reaction
      between soda lime and CO2 and the maximum temperature recorded in the system was
      42.1 degrees C. Under clinical conditions this should pose no threat of thermal
      injury to the patient.

PMID- 9659017
TI  - The influence of premedication on heart rate variability.
AB  - Analysis of heart rate variability has been used to study the effects of
      midazolam, morphine and clonidine on the autonomic nervous system, when
      administered to patients for premedication. Ninety-five patients were studied 60
      min before and 60 min after premedication. Normal saline (n = 25), midazolam 0.08
      mg.kg-1 (n = 24), morphine 0.15 mg.kg-1 (n = 23), or clonidine 2 micrograms.kg-1
      (n = 23) were administered intramuscularly by random allocation. A Holter device
      was connected to the patient during the study period. Using power spectral
      analysis the low-frequency and high-frequency components were calculated from the
      Holter recordings. These are markers for sympathetic and parasympathetic activity
      respectively; the low- to high-frequency ratio was also calculated, a ratio of >
      1 signifying sympathetic dominance. A significant reduction was noticed in both
      low-frequency and high-frequency power in the three premedicated groups, whereas
      no changes were observed in the normal saline group. In the case of midazolam,
      both the low and high frequencies were decreased but the low- to high-frequency
      ratio did not change significantly. Morphine and clonidine depressed the low
      frequency component more than the high-frequency component and the low- to high
      frequency ratio was decreased, suggesting parasympathetic dominance. We conclude
      that heart rate variability may be a useful tool for investigating the effect of
      drugs on the autonomic nervous system.

PMID- 9659019
TI  - Experiences and attitudes of consultant and nontraining grade anaesthetists to
      continuing medical education (CME).
AB  - A questionnaire survey was sent to 164 consultant anaesthetists with the aim of
      investigating their experiences and attitudes to continuing medical education.
      The response rate was 79%. Most anaesthetists were motivated to achieve the
      required number of credits and for the majority of anaesthetists, regional,
      national and internal departmental discussion meetings were the mainstay of
      educational activities. The educational standard of available activities could be
      improved to include more workshop-style learning opportunities and to make
      journal reading a creditable continuing medical education activity. The place of
      research is questioned. There was doubt as to whether sanctions such as
      withdrawing recognition for training should be imposed on departments where some
      anaesthetists fail to achieve the required number of credits and whether this
      would motivate anaesthetists to achieve the set standards. Continuing medical
      education was felt to be effective and the main barriers to attending educational
      activities are discussed.

PMID- 9659020
TI  - Pain on injection of propofol.
AB  - Pain on injection of propofol is a common problem, the cause of which remains
      unknown. The chemical properties and preparation of propofol, proposed mechanisms
      for the cause of the pain and clinical strategies to prevent pain on injection of
      propofol are reviewed in the hope of shedding some light on the subject.

PMID- 9659021
TI  - Complications of percutaneous dilatational tracheostomy in children.
AB  - Experience with percutaneous dilatational tracheostomy in children is limited.
      This report discusses two significant complications which occurred following the
      use of this technique.

PMID- 9659022
TI  - The cuffed oropharyngeal airway as an aid to fibreoptic intubation.
AB  - The cuffed oropharyngeal airway is a new disposable airway based on the Guedel
      oral airway. It has an asymmetrical cuff which provides a seal as well as lifting
      the base of the tongue forwards, and a 15-mm connector allowing attachment to an
      anaesthetic breathing system. The device does not extend beyond the vallecula, so
      that the laryngeal inlet can be visualised with a fibreoptic laryngoscope passed
      between the cuff of the device and the pharyngeal wall. The advantage is that
      ventilation is maintained throughout the intubating sequence. We describe its use
      in a patient with oropharyngeal carcinoma.

PMID- 9659023
TI  - Caesarean section following a recent retinal haemorrhage.
AB  - We report a case of a 32-year-old woman who developed an antenatal Valsalva
      induced retinal haemorrhage causing unilateral blindness 38 weeks into her
      pregnancy. Delivery was achieved by elective Caesarean section under epidural
      anaesthesia. The influence of anaesthetic technique on a recent retinal
      haemorrhage is discussed.

PMID- 9659024
TI  - The effects of volume and speed of injection in peribulbar anaesthesia.
AB  - We have evaluated the effects of the volume and speed of administration of local
      anaesthetic during peribulbar anaesthesia. One hundred and forty patients
      scheduled for cataract surgery were randomly allocated to one of four groups of
      35. Each patient received an injection of the same mixture of lignocaine,
      bupivacaine and hyaluronidase. Patients in group A were given 9 ml at a speed of
      5 ml.min-1, group B were given the same volume at 12 ml.min-1, group C were given
      13.5 ml at 5 ml.min-1 and group D were given 13.5 ml at 12 ml.min-1. A
      significantly higher incidence of satisfactory akinesia was found in group D,
      whose pain score at injection was no higher than for the other groups. Large
      volumes of local anaesthetic significantly affected intra-ocular pressure. The
      incidences of early and late ptosis or diplopia were not affected by either the
      rate of injection or the volume of local anaesthetic.

PMID- 9659025
TI  - The use of low-dose mivacurium to facilitate insertion of the laryngeal mask
      airway.
AB  - Ninety patients were assigned randomly in a double-blind manner to receive 0.9%
      sodium chloride, mivacurium 0.04 mg.kg-1 or mivacurium 0.08 mg.kg-1
      intravenously, followed by propofol 2.5 mg.kg-1. A laryngeal mask airway (LMA)
      was inserted 90 s later. The LMA was positioned correctly during the first
      attempt in 87% of patients and this was not significantly altered by the use of
      mivacurium. However, mivacurium decreased the incidence of swallowing, coughing,
      movement and laryngospasm (p < 0.05). LMA insertion was graded as easy in 88% of
      patients who had mivacurium, compared with 50% in patients who had propofol alone
      (p < 0.05). The conditions during LMA insertion were similar after 0.04 or 0.08
      mg.kg-1 of mivacurium. Patients were apnoeic for a mean (SD) time of 0.67 (0.72)
      min after propofol alone, compared with 1.72 (1.06) min and 3.05 (1.36) min in
      patients who also received mivacurium 0.04 and 0.08 mg.kg-1, respectively (p <
      0.01). Patients who received mivacurium had a lower incidence of postoperative
      sore throat (24-30% vs. 53%) (p < 0.05). In conclusion, low-dose mivacurium
      facilitates LMA insertion and decreases the incidence of postoperative sore
      throat.

PMID- 9659026
TI  - Comparison of pain from insertion of venous cannulae; a volunteer study.
AB  - The pain from insertion of two small cannulae was compared in 26 volunteers. Each
      subject was blindfolded and had both a 22 G and a 20 G cannula inserted in random
      order. One subject was rejected as cannulation was unsuccessful. Of the remaining
      25 subjects, 12 found the 22 G more painful and 13 the 20 G. This difference was
      not significant (chi squared p > 0.1).

PMID- 9659027
TI  - Exogenous adenosine potentiates hypnosis induced by intravenous anaesthetics.
AB  - We investigated the effect of adenosine on hypnosis induced by thiopentone,
      propofol and midazolam in mice. The onset and duration of hypnosis were
      determined by the loss of righting reflex. Adenosine and 2-chloroadenosine caused
      a significant shortening of onset of sleep-time and prolongation of duration of
      sleep-time in all groups (p < 0.05). Dipyridamole administration before combined
      intravenous anaesthetic-adenosine or intravenous anaesthetic-2-chloroadenosine
      administration produced similar effects to adenosine (p < 0.05). The adenosine
      antagonist theophylline, given before intravenous anaesthetic-adenosine or
      intravenous anaesthetic-2-chloroadenosine administration caused a significant
      delay in onset of sleep-time and shortening in the duration of sleep-time (p <
      0.05). We conclude that central excitatory noradrenergic neurones play an
      important role in adenosine, 2-chloroadenosine and dipyridamole-induced hypnotic
      responses to intravenous anaesthetics and their inhibition by adenosine
      antagonists.

PMID- 9659028
TI  - The effect of mivacurium pretreatment on intra-ocular pressure changes induced by
      suxamethonium.
AB  - Forty patients without eye disease, undergoing elective nonophthalmic surgery,
      were studied in a double-blind, randomised, placebo-controlled study evaluating
      the efficacy of mivacurium pretreatment in attenuating the rise in intra-ocular
      pressure in response to suxamethonium administration, laryngoscopy and
      intubation. The patients were randomly allocated to receive either mivacurium
      0.02 mg.kg-1 or normal saline as pretreatment 3 min before a rapid sequence
      induction technique using alfentanil, propofol and suxamethonium. Suxamethonium
      induced a significant increase in intra-ocular pressure in the control group but
      not in the mivacurium pretreatment group (mean (SEM) increase = 3.5 (1.2) mmHg
      vs. 0.4 (0.8) mmHg, p < 0.05). There was a decrease in intra-ocular pressure in
      both groups after laryngoscopy and intubation with no significant difference
      between the two groups. These results show that mivacurium pretreatment is
      effective in preventing the increase in intra-ocular pressure after suxamethonium
      administration.

PMID- 9659029
TI  - The efficacy of ginger root in the prevention of postoperative nausea and
      vomiting after outpatient gynaecological laparoscopy.
AB  - To determine the anti-emetic effect of ginger as compared to droperidol, 120
      patients scheduled to have gynaecological diagnostic laparoscopy as day cases
      were randomly allocated into placebo, droperidol, ginger and ginger plus
      droperidol groups to receive either 2 g of ginger or 1.25 mg of droperidol or
      both. There were no significant differences in the incidences of postoperative
      nausea which were 32%, 20%, 22% and 33%, and vomiting which were 35%, 15%, 25%
      and 25% in the four groups, respectively. We conclude that ginger powder, in the
      dose of 2 g, droperidol 1.25 mg or both are ineffective in reducing the incidence
      of postoperative nausea and vomiting after day case gynaecological laparoscopy.

PMID- 9659030
TI  - Ephedrine/Epinephrine drug label confusion.

PMID- 9659031
TI  - Thoracic epidural analgesia and coronary artery bypass graft surgery.

PMID- 9659032
TI  - Thoracic epidural analgesia and coronary artery bypass graft surgery.

PMID- 9659033
TI  - A simple approach to dosing in children.

PMID- 9659034
TI  - Asthma: a plea for commonsense.

PMID- 9659035
TI  - Ilioinguinal nerve block for orchidopexy.

PMID- 9659036
TI  - Self-administration of pre-operative analgesic suppositories.

PMID- 9659037
TI  - Sevoflurane and adult acute epiglottitis.

PMID- 9659038
TI  - Warning notice above beds.

PMID- 9659039
TI  - Old habits, the circle system and short procedures.

PMID- 9659040
TI  - High-frequency ventilation for management of respiratory complications after
      trauma and major orthopaedic surgery.

PMID- 9659041
TI  - Management of traumatised patients in the ICU.

PMID- 9659042
TI  - Portable cardiopulmonary support (ECPS) in the emergency room.

PMID- 9659043
TI  - Transoesophageal echocardiography and volume management in the intensive care
      unit.

PMID- 9659044
TI  - The stress response and its modification by regional anaesthesia.

PMID- 9659045
TI  - Haemodynamic changes during surgery in the knee-elbow position: a
      transoesophageal echo-Doppler study.

PMID- 9659046
TI  - The use of ropivacaine in brachial plexus anaesthesia.

PMID- 9659047
TI  - Sciatic nerve blocks: approaches, techniques, local anaesthetics and
      manipulations.

PMID- 9659048
TI  - Anaesthetic techniques for knee arthroscopy.

PMID- 9659049
TI  - Continuous brachial plexus blockade via the vertical infraclavicular approach.

PMID- 9659051
TI  - Regional anaesthesia for low back operations.

PMID- 9659050
TI  - Interscalene brachial plexus block combined with total intravenous anaesthesia
      and laryngeal mask airway for shoulder surgery.

PMID- 9659052
TI  - Spinal anaesthesia: hearing loss, failure, transient radicular irritation (TRI).

PMID- 9659053
TI  - Blood substitutes: is it time for work process redesign in transfusion medicine?

PMID- 9659054
TI  - Predeposit, intentional peri-operative haemodilution and erythropoietin level in
      major orthopaedic surgery.

PMID- 9659055
TI  - Autotransfusion: role of perioperative blood salvage and predeposit.

PMID- 9659056
TI  - Blood saving in children.

PMID- 9659057
TI  - New developments in autologous transfusion systems.

PMID- 9659058
TI  - Pathophysiology and management of the fat embolism syndrome.

PMID- 9659059
TI  - The peri-operative management of major orthopaedic procedures.

PMID- 9659061
TI  - Practicability and safety of intra-operative autotransfusion with irradiated
      blood.

PMID- 9659060
TI  - Spinal cord monitoring.

PMID- 9659062
TI  - Heat loss during major orthopaedic surgery.

PMID- 9659064
TI  - Organisation and methods in postoperative pain therapy.

PMID- 9659063
TI  - Hypothermia prevention and treatment.

PMID- 9659065
TI  - Spinal sufentanil.

PMID- 9659066
TI  - Postoperative pain management in day surgery.

PMID- 9659067
TI  - Antithrombin (AT) substitution: sense or nonsense?

PMID- 9659068
TI  - Coagulation support: fresh frozen plasma versus clotting factor concentrate.

PMID- 9659069
TI  - Thromboembolic complications and pharmacological prophylaxis in orthopaedic
      surgery.
AB  - Two thousand, three hundred and three patients who had undergone major
      orthopaedic surgery were statistically analysed for the incidence of
      complications comparing three regimens of prophylaxis and coexisting diseases;
      2090 patients did not present postoperative complications. PTE occurred in 0.65%
      (one fatal). The mortality rate was 0.34% and the incidence of haemorrhage
      (haematoma and one gastric haemorrhage) was 3.8%. Patients treated with indobufen
      had a shorter hospital stay and the need for homologous blood transfusions was
      lower than for patients treated with calcium heparin. The rate of PTE was notably
      different in the three groups, being lower in the group treated with enoxaparin,
      although this result was not found to be statistically significant.

PMID- 9659070
TI  - Interactions between epidural analgesia and antifibrinolytics.

PMID- 9659071
TI  - Point-of-care coagulation monitoring: applications of the thromboelastography.

PMID- 9659072
TI  - Consensus use of desmopressin and antifibrinolytics in three university clinics.

PMID- 9659073
TI  - Acute peripheral ischaemia and compartment syndromes: a role for hyperbaric
      oxygenation.

PMID- 9659074
TI  - Severe trauma and infections.

PMID- 9659075
TI  - Hyperbaric oxygen therapy in osteomyelitis.

PMID- 9659077
TI  - Loco-regional anaesthesia and trauma in children: what can we do in the emergency
      room?

PMID- 9659076
TI  - Principles in peri-operative paediatric medicine.

PMID- 9659078
TI  - Ropivacaine for central blocks in children.

PMID- 9659079
TI  - Stress response in orthopaedics and trauma in paediatrics: general versus
      regional anaesthesia.

PMID- 9659080
TI  - Anaesthesia in handicapped children.

PMID- 9659081
TI  - Echocardiography on the neonatal unit: a job for the neonatologist or the
      cardiologist?

PMID- 9659082
TI  - Licensing of medicines.

PMID- 9659083
TI  - Epidemiology of head injury.

PMID- 9659084
TI  - Evidence-based dilemmas in pre-school vision screening.

PMID- 9659085
TI  - A prospective 10 year follow up study of patients with neurofibromatosis type 1.
AB  - OBJECTIVE: To establish the prevalence and incidence of symptoms and
      complications in children with neurofibromatosis type 1 (NF1) and to assess
      possible risk factors for the development of complications. DESIGN: A 10 year
      prospective multidisciplinary follow up study. PATIENTS: One hundred and fifty
      children diagnosed with NF1 according to criteria set by the National Institutes
      of Health. RESULTS: In 62 of 150 children (41.3%) complications were present,
      including 42 (28.0%) children with one complication, 18 (12.0%) with two
      complications, and two (1.3%) with three complications (mean (SD) duration of
      follow up 4.9 (3.8) years). Ninety five of the 150 children presented without
      complications (follow up, 340.8 person-years). The incidence of complications was
      2.4/100 person-years in this group. An association was found between behavioural
      problems and the presence of complications. CONCLUSION: This is the largest
      single centre case series of NF1 affected children followed until 18 years of
      age. Children with NF1, including those initially presenting without
      complications, should have regular clinical examinations.

PMID- 9659086
TI  - Sleep and psychological disturbance in nocturnal asthma.
AB  - Subjective and objective sleep disturbance was studied in children with nocturnal
      asthma. Relations between such disturbance and daytime psychological function
      were also explored, including possible changes in learning and behaviour
      associated with improvements in nocturnal asthma and sleep. Assessments included
      home polysomnography, parental questionnaires concerning sleep disturbance,
      behaviour, and mood and cognitive testing. Compared with matched controls,
      children with asthma had significantly more disturbed sleep, tended to have more
      psychological problems, and they performed less well on some tests of memory and
      concentration. In general, improvement of nocturnal asthma symptoms by changes in
      treatment was followed by improvement in sleep and psychological function in
      subsequent weeks. The effects of asthma on sleep and the possible psychological
      consequences are important aspects of overall care.

PMID- 9659087
TI  - Iron status of Asian children aged 2 years living in England.
AB  - Haemoglobin and ferritin values were analysed in blood from 1057 children, aged 2
      years, of Asian parents living in England. Children who had thalassaemia trait or
      a current/recent infection were excluded. Twenty nine per cent of Pakistani, 25%
      of Bangladeshi, and 20% of Indian children had haemoglobin < 110.0 g/l. The
      recent national diet and nutrition survey of preschool children found a
      prevalence of 12% of 2 year olds with haemoglobin < 110.0 g/l. No single factor
      accounted for more than a small proportion of the variance in haemoglobin and
      ferritin values, but the most significant factors that had a negative effect on
      iron status included the amount of cows' milk consumed, the use of a baby bottle,
      and mother's place of birth being outside of the UK. Taking vitamin or iron
      supplements was positively associated with iron status in one or more of the
      three groups.

PMID- 9659088
TI  - Health at age 11: reports from schoolchildren and their parents.
AB  - OBJECTIVE: To present self reports by children and reports by parents on behalf
      of their children relating to general health, current conditions, and recent
      symptoms. DESIGN: Questionnaires completed by children and parents as part of the
      longitudinal "West of Scotland 11 to 16 study: teenage health." SETTING: 135
      primary schools in Central Clydeside. SUBJECTS: 2586 children aged 11 years,
      surveyed from October 1994 to March 1995 (response rate 93%). Questionnaires also
      completed by parents of 86% of the sample. MAIN OUTCOME MEASURES: Ratings of
      health over the past 12 months, presence of (limiting) longstanding illness, nine
      current conditions, and 11 recent symptoms. RESULTS: Only 47% of children
      described their health as "good" in the previous year. Around 20% reported a
      longstanding illness and 8% a limiting illness; 20% reported migraine or
      headaches, 13% reported asthma. Recent stomach aches or sickness, colds or flu,
      and headaches were each reported by around 60%. "Malaise" (emotional) symptoms
      were common. Parents reported similar levels of (limiting) longstanding illness,
      but rates of conditions and symptoms reported by parents were lower than reported
      by their children. Parent-child agreement was greatest for the presence of
      longstanding illness and the conditions of asthma, diabetes, and skin problems.
      It was lower for recent symptoms, particularly those categorised as reflecting
      malaise. CONCLUSIONS: These results challenge assumptions of good health and
      wellbeing at this age. Illness reporting depends on various factors, including
      saliency, social desirability, and definitions of normality. Parent-child
      discrepancies may reflect different definitions of illness or symptoms; they do
      not mean that one should be dismissed as "wrong."

PMID- 9659089
TI  - Mortality and diabetes from a population based register in Yorkshire 1978-93.
AB  - OBJECTIVE: To investigate mortality of children diagnosed with insulin dependent
      diabetes mellitus (IDDM) and to identify common factors before death. DESIGN:
      Follow up of a population based cohort of children diagnosed with IDDM to
      ascertain deaths. SETTING: Children were diagnosed in Yorkshire but followed up
      throughout the United Kingdom. SUBJECTS: From the Yorkshire Children's Diabetes
      Register details of 1854 children aged 0-16 years (1978-93) were submitted to the
      NHS Central Register. MAIN OUTCOME MEASURE: Notification and causes of death.
      RESULTS: 98.3% of cases were traced and 26 deaths identified. Follow up ranged
      from 1-18 years (median 9.3 years), providing 17,350 person-years of IDDM.
      Fifteen deaths (58%) were attributed to diabetes or its complications; 11 (42%)
      were unrelated and included one suicide. For mortality from all causes, the
      standardised mortality ratio (SMR) of 247 (95% confidence interval (CI) 163 to
      362) was significantly increased for those under 34 years. The largest number of
      deaths (n = 10) occurred in the 15-19 year age range, with an SMR of 442 (95% CI
      209 to 802). Case note examination showed a clear tendency towards poor diabetic
      control, and worries over control were expressed before death by health care
      professionals. CONCLUSIONS: Despite advances in treatment, IDDM still carries an
      increased mortality for young people, particularly in the "transition" age range.

PMID- 9659090
TI  - Social adversities and anxiety disorders in the Gaza Strip.
AB  - AIM: To investigate the rate and nature of anxiety symptoms and disorders in
      children, and their relation to social adversities in a cultural sample not
      previously researched. METHODS: 237 children aged 9 to 13 years living in the
      Gaza Strip were selected randomly from 112 schools. Children completed the
      revised manifest anxiety scale (a questionnaire with yes/no answers for 28
      anxiety items and nine lie items), and teachers completed the Rutter scale (a
      questionnaire of 26 items of child mental health problems rated on a scale of 0
      2: "certainly applies", "applies somewhat", "doesn't apply"). RESULTS: Children
      reported high rates of significant anxiety problems (21.5%) and teachers reported
      high rates of mental health problems in the children (43.4%) that would justify
      clinical assessment. Anxiety problems, particularly negative cognitions,
      increased with age and were significantly higher among girls. Low socioeconomic
      status (father unemployed or unskilled worker) was the strongest predictor of
      general mental health problems. Living in inner city areas or camps, both common
      among refugees, was strongly associated with anxiety problems. CONCLUSIONS: The
      rate and nature of anxiety disorders were similar to those established in Western
      societies. Factors reflecting social adversity and lack of stability were also
      similarly involved. There may be more similarities in the presentation of mental
      health symptoms across cultures than previously believed.

PMID- 9659091
TI  - Relation between dietary intake and nutritional status in cystic fibrosis.
AB  - This study evaluated adherence to current dietary recommendations of children
      with cystic fibrosis and mild lung disease and their siblings by comparing energy
      intake. Fifty children (25 with cystic fibrosis) aged between 7 and 12 years
      completed the study. Energy intake was assessed by weighed dietary intake,
      resting energy expenditure was used to calculate recommended daily intakes. The
      children with cystic fibrosis had significant deficits in Z scores for both
      height and weight compared with their siblings, but there was no difference in
      percentage of ideal weight for height. The cystic fibrosis group had a
      significantly higher energy intake per kilogram body weight per day but there was
      no difference in the percentage of energy derived from fat, protein or
      carbohydrate. Energy intake (per kg/day) and fat intake (g/kg) were both
      significant predictors of weight for height in the cystic fibrosis group. Targets
      for dietary management in cystic fibrosis should perhaps be related to fat intake
      per kilogram body weight.

PMID- 9659092
TI  - Serum eosinophilic cationic protein may predict clinical course of wheezing in
      young children.
AB  - Thirty eight children aged between 2 and 4 years with three or more episodes of
      wheezing were studied to evaluate the role of eosinophil inflammation and its
      relation to persistence of wheezing two years later. Serum eosinophilic cationic
      protein, total eosinophil count, total IgE, skin prick test, and clinical
      features were evaluated at visit 1. Two years later at a second clinical
      evaluation the children were separated into two groups: group 1, those with
      persistent wheezing (n = 20); group 2, those who had been asymptomatic over the
      past six months (transient wheezing) (n = 18). Mean (SEM) eosinophilic cationic
      protein at visit 1 was higher in group 1 than in group 2 (29.63 (5.16) v 14.42
      (2.77) micrograms/l), and the probability of continuing wheezing at age 5 years
      was greater in children with values > or = 20 micrograms/l at visit 1 than in
      those with lower values (relative risk = 2.88, 95% confidence interval 1.42 to
      5.87, p < 0.001). Eosinophil inflammation is present from the beginning of the
      disease in the children who are going to continue with wheezing at age 5 years.
      The measurement of serum eosinophilic cationic protein may help in evaluating
      which wheezing infants are going to continue with asthma in the future.

PMID- 9659093
TI  - Randomised controlled trial of sucrose by mouth for the relief of infant crying
      after immunisation.
AB  - OBJECTIVES: To evaluate the effect of sucrose solution given by mouth on infant
      crying times and measures of distress in the immunisation clinic. DESIGN:
      Randomised, double blind, placebo controlled trial of sucrose solution 75% wt/vol
      v sterile water as a control. SETTING: The immunisation clinic of the Women's and
      Children's Hospital, Adelaide. PATIENTS: A total of 107 healthy infants attending
      for 2, 4, or 6 month immunisations with polio by mouth (Sabin), intramuscular
      diphtheria, tetanus, and pertussis (DTP), and intramuscular Haemophilus
      influenzae type b were randomised to receive 2 ml 75% sucrose solution or sterile
      water by mouth before the two injections. METHODS: The duration of infant crying
      was recorded during and immediately after two intramuscular immunisations and
      infant distress was assessed by a visual analogue scale (Oucher scores)
      independently by a nurse and a parent. RESULTS: The administration of 2 ml 75%
      sucrose solution by mouth reduced the infant crying time and Oucher distress
      scores after immunisation with DTP/H influenzae type b. CONCLUSIONS: Infant
      immunisation by intramuscular injection is a distressing procedure for infants
      and parents. Sucrose solution at a high concentration reduces infant distress and
      is safe and clinically useful in this setting.

PMID- 9659094
TI  - Use of pulse oximetry for blood pressure measurement after cardiac surgery.
AB  - Blood pressure measurement using pulse oximeter waveform change was compared with
      an oscillometric measurement and the gold standard, intra-arterial measurement,
      in children after cardiac surgery. Forty six patients were enrolled and divided
      into groups according to weight. Simultaneous blood pressure measurements were
      obtained from the arterial catheter, the oscillometric device, and the pulse
      oximeter. Pulse oximeter measurements were obtained with a blood pressure cuff
      proximal to the oximeter probe. The blood pressure measurements from the pulse
      oximeter method correlated better with intra-arterial measurements than those
      from the oscillometric device (0.77-0.96 v 0.42-0.83). The absolute differences
      between the pulse oximeter and intra-arterial measurements were significantly
      smaller than between the oscillometric and intra-arterial measurements in
      children less than 15.0 kg. The pulse oximeter waveform change is an accurate and
      reliable way to measure blood pressure in children non-invasively, and is
      superior to the oscillometric method for small patients.

PMID- 9659095
TI  - Reference values for pulse oximetry at high altitude.
AB  - OBJECTIVE: To determine reference values for oxygen saturation (Sao2) in healthy
      children younger than 5 years living at high altitude. DESIGN: One hundred and
      sixty eight children were examined for Sao2 at 4018 m during well child visits.
      Physiological state was also noted during the examination. RESULTS: The mean Sao2
      was 87.3% (95% confidence intervals (CI) 86.7%, 87.9%) with a median value of
      87.7%. A significant difference was observed in Sao2 between children younger
      than 1 year compared with older children, although the difference was no longer
      demonstrable when sleeping children were excluded. CONCLUSIONS: This study has
      provided a reference range of Sao2 values for healthy children under 5 years old
      so that pulse oximetry may be used as an adjunct in diagnosing acute respiratory
      infections. Younger children were also shown to have a lower mean Sao2 than older
      children living at high altitude, which suggests physiological adaptation to high
      altitude over time. In addition, sleep had a lowering effect on Sao2, although
      the clinical importance of this remains undetermined.

PMID- 9659096
TI  - Chromosome aberrations in coeliac and non-coeliac enteropathies.
AB  - The frequency of chromosomal aberrations in peripheral blood lymphocytes was
      assessed in three groups of children: untreated coeliac disease (n = 20); non
      coeliac disease enteropathies (n = 15); controls (n = 15). The mean frequency of
      aberrant cells and the total number of aberrations per 100 metaphases was
      increased in the coeliac disease group compared with controls by factors of 5 and
      6, respectively (p < 0.01 for both). Aberrant cells and total aberrations were
      similarly increased in the non-coeliac disease enteropathy group by a factor of
      3.7 in each case (p < 0.05). However, the frequency of aberrations in the two
      enteropathy groups was not significantly different. Children with coeliac
      disease, similar to affected adults, have evidence of increased chromosomal
      instability. However, similarly increased chromosomal aberrations are seen in
      children with non-coeliac disease enteropathies, indicating that the abnormality
      is not specific for coeliac disease.

PMID- 9659097
TI  - Growth hormone replacement in patients with Langerhan's cell histiocytosis.
AB  - OBJECTIVES: To assess the impact of growth hormone on growth and the underlying
      disease in children with growth hormone deficiency as a result of Langerhan's
      cell histiocytosis. STUDY DESIGN: Retrospective analysis of data from the Kabi
      (Pharmacia & Upjohn) international growth database (KIGS) for 82 children with
      Langerhan's cell histiocytosis treated with recombinant growth hormone. RESULTS:
      At the start of treatment the median (10-90th centile) age was 9.0 (5.2 to 14.7)
      years, with a median height standard deviation score (SDS) of -2.0 (-3.5 to 
      0.9). The median pretreatment height velocity (measured in cm/year) was 3.6 (0.9
      to 6.4); this increased to 8.8 (3.8 to 12.0) in the first year of treatment with
      growth hormone, and then remained significantly greater than the pretreatment
      height velocity at 7.3 (4.4 to 9.7) and 7.1 (4.1 to 9.3) cm/year in the second
      and third years, respectively. The median height SDS increased from -2.0 to -0.8
      (-2.3 to 0.6) by the end of three years of treatment. There was no increase in
      the recurrence rate of the underlying disease and no adverse event could be
      directly attributed to growth hormone treatment, apart from one case of benign
      intracranial hypertension that resolved on stopping treatment with growth
      hormone. CONCLUSIONS: Growth hormone replacement treatment for patients with
      Langerhan's cell histiocytosis with growth hormone deficiency is beneficial and
      safe.

PMID- 9659099
TI  - Socioeconomic status and changes in body mass from 3 to 5 years.
AB  - The influence of social status on the development of body mass was analysed in a
      retrospective cohort study of 675 Belgian children monitored between the ages of
      3 and 5 years by the preventive medical services in Brussels. At age 3, no
      association between excess weight and social status was observed. Adiposity
      rebound before age 5 was inversely related to body mass at age 3 and was
      independent of social status. The social influences on obesity observed in
      adolescence cannot be explained by a higher frequency of early adiposity rebound
      in children of low socioeconomic status.

PMID- 9659098
TI  - Effect of growth hormone on height, weight, and body composition in Prader-Willi
      syndrome.
AB  - AIMS: To evaluate the effect of the administration of growth hormone on stature,
      body weight, and body composition in children aged between 4 and 10 years with
      Prader-Willi syndrome. METHODS: Height, weight, and skinfold thickness were
      recorded in 25 children using standard anthropometric techniques at recruitment,
      and six months later, shortly before the start of daily subcutaneous injections
      of growth hormone. Body composition was assessed via a measurement of total body
      water using stable isotopes. Measurements were repeated at the end of the six
      months of growth hormone administration. Measurements of height, weight, and
      skinfold thickness were expressed as standard deviation scores (SDSs). RESULTS:
      There was a significant reduction in the percentage of body fat after growth
      hormone treatment; height velocity doubled during treatment; body weight did not
      change significantly when expressed as an SDS. Skinfold thickness at both the
      triceps and subscapular site decreased in absolute terms and when expressed as an
      SDS. CONCLUSIONS: These results indicate sufficient potential benefit to justify
      a more prolonged trial of growth hormone treatment and an exploration of
      different dosage regimens in children with Prader-Willi syndrome.

PMID- 9659100
TI  - Mononucleosis syndrome and coincidental human herpesvirus-7 and Epstein-Barr
      virus infection.
AB  - Two girls (a 5 year old and a 21 month old) experiencing mononucleosis syndrome
      with coincidental human herpesvirus (HHV)-7 and Epstein-Barr virus (EBV)
      infections are described. One patient had primary HHV-7 infection and reactivated
      EBV infection. The other had primary HHV-7 and EBV infections. These cases
      indicated that HHV-7 is capable of inducing infectious mononucleosis-like
      illness. Multiple herpesvirus infection in one of the patients also suggests that
      interaction among herpesviruses can occur in vivo. The consequence of this
      interaction may have clinical implications.

PMID- 9659101
TI  - Neurocardiogenic syncope: a model for SIDS.
AB  - A 5 1/2 month old male infant who had suffered three acute life threatening
      episodes was admitted for overnight sleep studies but was found dead after their
      completion while still in hospital. A necropsy classified the cause of death as
      sudden infant death syndrome (SIDS). The sleep studies had shown no periods of
      apnoea (> 20 seconds) or bradycardia (< 90 beats/min), and a rapid response to
      nasal occlusion (5 seconds). However, autonomic function during sleep was poor,
      with reduced heart rate variability (6 beats/min v control 24 beats/min, SD 6.2)
      and postural hypotension (a 12-14% fall in resting systolic blood pressure)
      associated with a fall in heart rate when tilted to a vertical position. Postural
      hypotension with bradycardia occurs in adults with unexplained syncopal episodes
      and is called a neurocardiac reflex. It involves poor vasomotor tone with
      peripheral pooling of blood, a consequent reduction in central venous return and
      cardiac distension, and in some individuals a neurally mediated bradycardia, as
      seen in this infant, rather than the expected tachycardia. A progressive
      bradycardia is the predominant mechanism of death seen in SIDS infants dying on
      cardiorespiratory monitors at home. This case suggests that a neurocardiac reflex
      occurs in infants, may have been involved in this infant's death, and deserves
      further study in the context of SIDS.

PMID- 9659102
TI  - Teaching paediatrics for the developing world.

PMID- 9659104
TI  - Masculinism disguised as feminism.

PMID- 9659103
TI  - Molecular biology and genetics of allergy and asthma.

PMID- 9659105
TI  - Implementing a children's day assessment unit in a district general hospital.

PMID- 9659107
TI  - Sedation for invasive procedures in paediatrics.

PMID- 9659106
TI  - How often should we screen for hypothyroidism in girl's with Turner's syndrome?

PMID- 9659108
TI  - PLink, plastic surgery and the Internet.
AB  - The Internet is a fast growing, global computer network that is easy to access at
      a low cost. This form of communication allows rapid electronic exchange of
      information such as text, pictures, animations, video and sound. This offers
      physicians an opportunity to enhance the quality of patient care, research and
      communication with colleagues. Patients who previously had limited access to
      information concerning diseases and treatment options are now able to find
      medical information on the Internet. The quality of information found on the
      Internet varies widely, from the most up-to-date protocols, produced by leading
      physicians and surgeons, to out of date or inaccurate recommendations. Faced with
      an enormous quantity of information of variable quality, guidelines certified by
      recognised medical organisations are essential to provide websites with valuable
      information. This so-called "safe house principle" creates reliable places on the
      Internet ("safe houses") that are generally accepted and trusted for containing
      valid information. We have created such a "safe house" on plastic surgical topics
      for the Netherlands Society for Plastic Surgery called "PLink" (the Plastic
      Surgery link). Its goals are: 1. to provide a well-organised list of existing
      plastic surgery Internet resources; 2. to improve communication; and 3. to
      provide original information on plastic surgical subjects for patients and
      physicians. Professionals always review the content. Since July 1996 our files
      have been accessed over 1.3 million times in 17 months, with the visit rate
      increasing from 1470 in July 1996 to 4200 in March 1997 and remaining stable
      since then. This indicates that there is a growing need for high quality
      information on plastic surgery on the Internet.

PMID- 9659109
TI  - Endoscopically assisted tissue expander insertion using balloon dissection.
AB  - A method of tissue expander insertion using balloon dissection and endoscopy is
      presented. In tissue expander operations, accuracy and atraumatic techniques are
      important for preventing complications, and the endoscopic balloon provides safer
      and faster dissection of the fascial plane than can be achieved with endoscopic
      scissors, allowing the creation of subcutaneous pockets for tissue expander
      placement. The balloon can separate loose areolar tissue between deep and
      superficial fascia, forming a fascial cleft. The procedure has been used in 10
      cases with satisfactory results.

PMID- 9659110
TI  - The distally based lateral adipofascial flap.
AB  - The distally based lateral adipofascial flap can be based either on the lowermost
      perforator or the anterior perforating branch of the peroneal artery avoiding
      sacrifice of the main peroneal artery. It has been used successfully to resurface
      soft tissue defects either on the lateral or medial aspect of the lower third of
      the leg in 13 cases. The size of these flaps varied from 2.0 cm x 5.0 cm to 4.5
      cm x 15.0 cm in size. These cases had minimal donor site morbidity and had
      positive aesthetic results. The advantages were: 1. Choice of either the
      lowermost perforator or the anterior perforating branch giving a wide arc of
      rotation; 2. Preservation of the superficial peroneal nerve; 3. Primary closure
      of the donor site.

PMID- 9659111
TI  - Expansion of the oral end of free revascularised jejunum with a jejunal patch
      flap rotated like a folding fan.
AB  - We have devised a new expansion process for the reconstruction of the cervical
      oesophagus with free revascularised jejunum in cases of hypopharyngeal cancer.
      The jejunal island flap is divided into three subislands and the major island of
      the caudal end is split partially at its oral end. The middle island is split,
      trimmed triangularly, and inserted into opened major island to expand the
      diameter of the oral end of the conduit for the cervical oesophagus and to make
      it funnel-shaped. The smallest island on the oral side is used as a circulation
      monitor for the transferred jejunum. Because the jejunal island patch is rotated
      around the root of mesentery like a folding fan and joined to the major island,
      there is neither shortening of the pedicle nor distortion. This method allows
      expansion of the oral end by up to 180% to facilitate end to end anastomosis in
      proximal pharyngeal defects.

PMID- 9659112
TI  - Application of reduction mammaplasty in treatment of giant breast tumour.
AB  - Reduction mammaplasty has been the traditional method for managing breast
      hypertrophy or severe ptosis in the field of plastic surgery. We describe two
      patients with giant breast hamartomas treated with the application of reduction
      mammaplasty by either the superior or inferior pedicle technique. Both had
      satisfactory results with symmetry of breast projection and nipple-areola complex
      placement. Standard plastic surgical techniques may be effectively applied in the
      treatment of giant breast tumours which compromise the aesthetic appearance of
      the breast.

PMID- 9659113
TI  - The lateral thigh V-Y flap for the repair of ischial defects.
AB  - The lateral thigh fasciocutaneous flap described by Maruyama et al in 1984 is a
      useful method for the repair of ischial and trochanteric defects. We clinically
      re-evaluated the potential vascular territory of the nutrient artery for this
      flap, i.e., the first profunda perforator, and have newly designed the postero
      lateral thigh V-Y flap in the area including the proximal two-thirds of the
      posterior thigh. This flap was applied to five difficult or recurrent ischial
      defects, and satisfactory results were obtained in all cases. For the
      reconstruction of ischial defects, the postero-lateral thigh V-Y flap has the
      following advantages; the proximal and well-vascularised portion of the flap is
      inserted into the area of the previously excised pressure sore, and this flap can
      potentially be readvanced if a recurrent pressure sore should develop. A Z-plasty
      can be performed to prevent excessive tension on the skin closure at the junction
      of the V-Y advancement flap. The postero-lateral thigh V-Y flap can be considered
      one of the first-line options for both primary and recurrent ischial pressure
      sores.

PMID- 9659114
TI  - Evaluation of new improved solution containing trehalose in free skin flap
      storage.
AB  - BACKGROUND DATA: In this study, we evaluated a new intracellular type (IT-K)
      solution containing trehalose in a rabbit free skin flap storage model. Trehalose
      is a nonreducing disaccharide that can stabilise cell membranes under various
      stressful conditions. MATERIAL AND METHOD: Seventy-two free skin flaps of the ear
      of rabbits were preserved in Euro-Collins (EC) solution or in IT-K solution for
      24, 48, and 72 h at 4 degrees C. After completion of preservation, these flaps
      were replanted to the other ear by microsurgical techniques. Viability study and
      photo documentation were performed daily for 7 days. Tissue specimens were taken
      24 h after vascular anastomosis, fixed in 10% formaldehyde and stained with
      haematoxylin and eosin (HE). Survival rates were analysed by Fisher's exact test
      for comparison of the two experimental groups. Values of P < 0.05 were considered
      to be statistically significant. RESULTS: After 7 days, a survival rate of 100%
      of flaps were observed in both solutions after 24 h of preservation. After
      preservation for 48 h in IT-K solution the survival rate was 100%. However, in EC
      solution survival decreased to 75% (9 of 12 preserved flaps survived). This
      difference increased to 33.3% (4 of 12 flaps) in EC solution and 91.6% (11 of 12
      flaps) (P < 0.01) in IT-K solution when the flaps were stored for 72 h. Light
      microscopic examination also showed less damage in flaps preserved in IT-K
      solution than in these preserved in EC solution. CONCLUSION: IT-K solution was
      superior to EC solution in the preservation of free skin flaps on rabbit ears
      when stored for 48 and 72 h.

PMID- 9659115
TI  - An inexpensive self fabricated pressure clip for the ear lobe.
AB  - Pressure therapy is an integral part of keloid treatment. There are certain areas
      of the body which are prone to keloid formation but are not amenable to pressure
      therapy. The ear lobe is one such area. A simple, self fabricated and inexpensive
      pressure clip has been used for applying postoperative pressure to the ear lobe.
      This is fabricated with cold-cure poly methyl methacrylate and orthodontic wire.
      This has been used in 41 ear lobe keloids in 26 patients along with
      postexcisional triamcinolone acetonide therapy, 5 ear lobe reconstructions and 2
      cases of ear lobe clefts over a period of 8 years. Although these clips are not
      very aesthetic, still the acceptability is very high as the patients were well
      motivated. A total of 27 ear lobes in 18 patients of ear lobe keloids have
      undergone ear boring after 6-18 months of pressure therapy. The only complication
      noticed is in the form of pressure ulcer due to continuous pressure in two
      patients at the beginning of our experience with these clips. These healed well
      after temporarily stopping the use of the clip.

PMID- 9659116
TI  - 'Tusked' forceps for rapid and atraumatic subcuticular closure of the skin.
AB  - A modified skin forceps is presented that combines the advantages of skin hook
      and dressing forceps. Its use facilitates the atraumatic placement of continuous
      intradermal sutures by the surgeon who is working unassisted.

PMID- 9659117
TI  - Thumb reconstruction, after Marjolin's ulcer resection by microvascular transfer
      of a burn-contracted little finger: a case report of spare part surgery.
AB  - Thumb reconstruction after amputation due to a squamous cell carcinoma in a burn
      scar sustained in infancy was accomplished by microvascular transfer of the
      ipsilateral scar-contracted little finger. This transfer achieved a successful
      functional and aesthetic thumb reconstruction and at the same time removed a
      'cumbersome' little finger which had often snagged on things. This case
      emphasises the merits of unused part transfer in hand reconstructive surgery,
      made possible by microvascular techniques.

PMID- 9659118
TI  - Reversed extensor indicis proprius muscle and dorsal wrist pain.

PMID- 9659119
TI  - Achieving natural shading of the nostril in the reconstruction of a half nose.
AB  - The secondary deformities in a patient who had a half nose that had been
      reconstructed in childhood using a median forehead flap and the corrective
      procedures subsequently employed are described. The secondary deformities
      included elevation of the right alar rim and a completely visible nasal floor.
      These deformities were corrected with a scalping forehead flap and by changing
      the orientation of the reconstructed right nostril and nasal cavity. Nasal airway
      reconstruction may not always be needed, particularly in a congenital half nose
      such as described here. Instead, the aesthetic importance of the orientation of
      the reconstructed nasal cavity in order to obtain a normal shaded appearance in
      the nostril is emphasised.

PMID- 9659120
TI  - Development of ganglioneuroma following successful treatment for orbital
      rhabdomyosarcoma.
AB  - A female infant presented with a left orbital embryonal rhabdomyosarcoma at the
      age of 3 months. She was successfully treated for this tumour with chemo- and
      radiotherapy. Eight years later she developed a ganglioneuroma in the same area
      which was treated surgically, but recurred at the age of 19. Re-examination of
      all of the specimens using immunohistochemistry confirmed that the initial and
      successive diagnoses had been correct. Two further explanations for this rare
      sequence of events are considered: whether the initial biopsy had been
      unrepresentative of the whole tumour, or whether there had indeed been two
      separate tumours arising in the same area. The theories of this previously
      undocumented occurrence are discussed further.

PMID- 9659121
TI  - Congenital partial absence of the facial muscles.
AB  - Facial asymmetry in a newborn infant suggests various diagnoses, including birth
      trauma and congenital hemifacial microsomia. But congenital absence or hypoplasia
      of facial muscles has not been known except for the depressor anguli oris muscle
      (DAOM). The authors' experience with surgical treatment of congenital hypoplasia
      of the risorius, zygomaticus major and minor, and levator labii superioris
      muscles is presented. Congenital facial muscle absence is uncommon. Although the
      hypoplasia of the DAOM is known, this disease is not fully clarified. The authors
      report a case of congenital partial palsy of the face in which some facial
      muscles were absent although the facial nerve was normal.

PMID- 9659122
TI  - Friction burns to thigh caused by tourniquet.

PMID- 9659123
TI  - Aesthetic treatment of Romberg's disease with multiple implants of fragmented
      Gore-Tex soft tissue patch.

PMID- 9659124
TI  - Atypical presentation of cutaneous B-cell lymphoma.

PMID- 9659125
TI  - Ritual sprinkling as a source of recurrent infection in a skin graft donor site.

PMID- 9659126
TI  - Radiological management of venous thrombosis of the lower limb.

PMID- 9659127
TI  - Contrast media-induced nephrotoxicity--questions and answers.
AB  - The intravascular administration of contrast media (CM) can produce acute
      haemodynamic changes in the kidney characterized by an increase in renal vascular
      resistance and a decrease in the glomerular filtration rate (GFR). These changes
      may lead to clinically significant reduction in renal function in patients with
      pre-existing risk factors such as diabetic nephropathy, congestive heart failure
      and dehydration. The pathophysiology of the renal haemodynamic effects of CM
      involves activation of the tubuloglomerular feedback (TGF) mechanism and the
      modulation of the intrarenal production of vasoactive mediators such as
      prostaglandins, nitric oxide, endothelin and adenosine. The TGF response is
      osmolality-dependent and accounts for about 50% of the acute functional effects
      of high osmolar CM on the kidney. Reduction in the synthesis of the endogenous
      vasodilators nitric oxide and prostaglandins increases the nephrotoxicity of CM.
      Endothelin and adenosine play a crucial role in mediating the acute functional
      effects of CM. Antagonists of these mediators attenuate the reduction in renal
      function induced by contrast agents. Vacuolization of the cells of the proximal
      tubules and necrosis of those of the medullary ascending limbs of loops of Henle
      are the main structural effects of CM in the kidney. The reduction in renal
      function induced by CM could be minimized by the use of low osmolar CM and
      adequate hydration. The prophylactic administration of calcium channel blockers
      and adenosine antagonists such as theophylline may also offer some protective
      effect.

PMID- 9659128
TI  - Observer variation in plain radiography of the lumbosacral spine.
AB  - In this study, interobserver and intraobserver variations in the interpretation
      of plain radiographs of the lumbosacral spine were evaluated. Three radiologists
      independently interpreted the radiographs from 200 consecutive outpatients, aged
      13-93 years, mostly referred from general practitioners. Interobserver agreement
      was best for vertebral fractures, osteopenia, spondylolisthesis at L5-S1,
      lumbosacral junctional vertebra, reduced disc height at L4-S1 and osteophytes at
      L2-S1 (kappa 0.61-0.95), and poorest for spina bifida of S1, degenerative
      spondylolisthesis and facet joint arthrosis at T12-L4, sacroiliac joint
      arthrosis, narrow central spinal canal, film quality, and for decisions
      concerning evaluation of facet joints and spinal canal (kappa < 0.34). For
      several diagnoses, the number of abnormal findings differed significantly between
      observers (p < 0.05, McNemar's test), indicating different diagnostic thresholds.
      Intraobserver agreement in 36 reevaluated patients was fair to excellent for
      almost all variables (kappa > 0.46). Although some diagnoses related to low back
      pain were quite consistently evaluated, the substantial disagreement on many
      findings should alert clinicians and radiologists against overestimating the
      validity and usefulness of the examinations. To improve diagnostic consistency,
      it is important to reduce variation caused by different thresholds for
      abnormality.

PMID- 9659129
TI  - The effect of radiographic contrast media on human vascular smooth muscle cells.
AB  - The relation between intravascular radiographic contrast media (RCM) and
      myointimal hyperplasia after percutaneous transluminal angioplasty is not known.
      We have investigated the cytotoxic effects of RCM on human vascular smooth muscle
      cells (VSMCs) and their effect on the growth of these cells. The cytotoxic
      effects of RCM were studied using human VSMCs. The cells after being grown to
      confluency were exposed for 60 min to 250 mgI ml-1 of diatrizoate, ioxaglate,
      iopromide, iotrolan and saturated mannitol solutions. The control group was
      treated with only 15% fetal calf serum (FCS) containing medium. The viability of
      the cells was examined using the trypan blue exclusion test. The effect of RCM on
      growth was assessed by exposing the VSMCs after growth arrest, for either 15 or
      60 min to 250 mgI ml-1 of diatrozoate, ioxaglate, iopromide, iotrolan and
      saturated mannitol solution. There was no significant change in the viability of
      the VSMCs after 60 min exposure to iopromide, iotrolan, saturated mannitol
      solution, and after 15 min exposure to diatrizoate or ioxaglate. After exposure
      to diatrizoate or ioxaglate for 60 min, 16.5 +/- 2.2% or 9.2 +/- 2.6% dead cells
      were found, respectively (p < 0.05 versus control). In the growth assay of VSMCs,
      diatrizoate, ioxaglate and saturated mannitol solutions reduced the growth rate
      (p < 0.05 versus control). No significant change was observed with iopromide and
      iotrolan. In conclusion, ionic RCM have cytotoxic and cytostatic effects on VSMCs
      while non-ionic media have no effects. There is no direct stimulatory effect of
      contrast media on the growth of VSMCs. The cytotoxic and cytostatic effects of
      contrast media seems to be both osmolality and chemotoxicity dependent. Low
      osmolar non-ionic RCM are not likely to contribute to the mechanisms responsible
      for myointimal hyperplasia after angioplasty.

PMID- 9659130
TI  - Colour Doppler flow in normal axillary lymph nodes.
AB  - 81 women with carcinoma of the breast who underwent axillary nodal dissection
      were studied pre-operatively with colour Doppler ultrasound. The presence of
      colour Doppler flow was demonstrated in 83.6% of normal lymph nodes compared with
      87.5% of metastatic lymph nodes. Using the presence of colour Doppler signal as
      the sole diagnostic criterion for the diagnosis of metastasis gave a sensitivity
      of 92.5%, specificity of 9.52%, accuracy of 50%, positive predictive value of
      49.3% and negative predictive value of 57.1%. Using grey scale sonographic
      criteria, where a metastatic node was defined as a node with loss of central
      fatty hilum and/or eccentric cortical hypertrophy, a sensitivity of 79.5%,
      specificity of 94.0%, accuracy of 87.6%, positive predictive value of 91.2% and
      negative predictive value of 85.5% were obtained. Colour Doppler studies of the
      axillary nodes in a second group of 106 women who attended for breast cancer
      screening and had no significant breast or axillary pathology also showed colour
      Doppler signal in 86.7% of nodes. It is concluded that colour Doppler flow
      signals can be demonstrated in both normal and metastatic axillary lymph nodes,
      and is highly non-specific when used as the sole diagnostic criterion in the
      diagnosis of malignancy.

PMID- 9659131
TI  - Intrasplenic venous flow patterns demonstrated by Doppler ultrasound in patients
      with portal hypertension.
AB  - The flow pattern in the splenic vein has been previously reported in patients
      with portal hypertension, but with no reference to the flow within the
      intrasplenic venous radicles. Using Doppler ultrasound, this study describes the
      intrasplenic venous flow direction in 176 adult patients with intrahepatic portal
      hypertension. In our series, a normal flow pattern was maintained in all except
      four patients (2.3%) who had either reversed or dual venous drainage patterns
      resulting in trans-splenic portosystemic shunts. These abnormal patterns are
      Doppler signs of portal hypertension which might be associated with a higher risk
      of oesophageal variceal bleeding. It is recommended that the intrasplenic venous
      flow pattern should be assessed before surgical intervention involving the spleen
      in patients with portal hypertension.

PMID- 9659132
TI  - Comparison of the precision of two vertebral morphometry programs for the lunar
      EXPERT-XL imaging densitometer.
AB  - Comparative precision tests of the vertebral height measurement function of the
      Aberdeen Vertebral Morphometry System (AVMS) software and Lunar EXPERT-XL
      software were undertaken using four vertebrae from the same lateral spine dual
      energy X-ray absorptiometry (DXA) image of the same subject (male, 67 years). Two
      of the vertebrae were abnormal and two were normal. Three observers inexperienced
      in morphometry and one experienced observer took part in the study. Repeatability
      was obtained from 10 sequential measurements of the posterior, middle and
      anterior heights at the same sitting by the same observer. Intraobserver
      reproducibility compared the means of one set of measurements for all vertebrae
      with another taken 1 week later. Interobserver reproducibility compared the means
      of one set of measurements for all vertebrae from an experienced and an
      inexperienced observer, and from two inexperienced observers. The AVMS software
      had significantly higher (p < 0.05) repeatability (mean coefficient of
      variability, CV = 3.5%) than the Lunar software (mean CV = 5%), significantly
      higher (p < 0.01) intraobserver reproducibility (mean CV = 4.6%) than the Lunar
      software (mean CV = 8.5%), and significantly higher (p < 0.05) interobserver
      reproducibility (mean CV = 4.7%) than the Lunar software (mean CV = 7.5%). In
      conclusion, the new AVMS method possessed higher precision when measuring both
      abnormal and normal vertebrae and when used by both experienced and inexperienced
      observers.

PMID- 9659133
TI  - Radiation dose and diagnosticity of barium enema examinations by radiographers
      and radiologists: a comparative study.
AB  - With the current emphasis on the extension of the role of the radiographer,
      radiographers in some hospitals now undertake some of the procedures
      traditionally performed by radiologists. In the present study, dose-area product
      (DAP) measurements for over 1000 barium enema examinations performed by
      radiologists and radiographers were analysed and compared to ascertain whether
      there were significant differences in the radiation dose to the patient,
      depending on the category of staff performing the examination. All examinations
      were reported by a radiologist. The radiologist's reports were analysed against
      the known outcomes to compare the diagnosticity of the examination when carried
      out by the two categories of staff. The study shows that although radiographers
      are able to produce consistent diagnostic results, there is an increase in
      patient dose due to extra films taken for reporting, which may be difficult to
      justify. Measures for reducing the dose from this component of the examination
      were explored.

PMID- 9659134
TI  - An economic evaluation of the use of rare earth screens to reduce the radiation
      dose from diagnostic X-ray procedures in Israel.
AB  - In Israel the diffusion of rare earth screen technology has been limited. These
      screens could halve the radiation dose to the patient from diagnostic X-ray
      radiography, with little managerial effort and without being detrimental to the
      quality of the diagnostic image. We estimated the total effective dose from
      diagnostic film radiography capable of reduction by the use of rare earth
      screens, based on the number of hospital and ambulatory diagnostic X-ray
      procedures. This number was multiplied by the computed radiation dose per body
      site for a series of diagnostic procedures. The annual dose was approximately
      0.53 mSv per head, approximately half of which could be averted by the
      introduction of rare earth screen technology. Based on a fatality risk of 3% Sv
      1, it is estimated that the adoption of rare earth screen technology might reduce
      the annual incidence of cancer by some 93 cases, half of which would be fatal
      after an average latency period of 18.4 years. The cost of purchasing rare earth
      screens on a nationwide basis is approximately $3.0 million. This cost is
      outweighed by a saving of $9.6 million in X-ray tube replacement costs over the
      period 1997-2006. Government legislation enforcing the use of rare earth screens
      is essential, because of the lack of prestige associated with acquiring rare
      earth technology, as well as institutional reluctance to accept the external
      benefits of reduced morbidity and mortality and/or to extend budgetary time
      horizons.

PMID- 9659135
TI  - An image registration scheme applied to verification of radiation therapy.
AB  - The introduction of modern conformal radiation therapy techniques requires high
      geometric precision in treatment delivery which must be verified. For that
      purpose we have developed an automated system based on registration of portal and
      simulation (or planning) image pairs. The image registration is performed on
      anatomical features which are automatically extracted from the portal image. The
      portal image is then registered with a planning or simulation radiographic image
      which represents the geometric prescription for the treatment, using an optimized
      version of the chamfer matching algorithm. Subsequently, the magnitude of the
      radiation field displacement during treatment is measured by registering the
      prescribed and treated field boundaries. Algorithms based on chamfer matching and
      polygon matching have been used for the field boundary registration. Performance
      of the entire scheme was evaluated on a series of 15 portal images of a pelvic
      phantom representing various known degrees of the radiation field displacement.
      The measurements of the radiation field displacements performed by the automated
      system proved very reliable and after correction for systematic bias agreed to
      within 1.5 mm or 1 degree with the displacements applied. Second test series
      involved comparisons between the automated registrations and those performed
      manually/visually by an experienced human observer, on 31 portal images acquired
      during treatments of 18 pelvic patients. These tests showed close agreement (in
      80% of cases discrepancies were smaller than 1.5 mm or 1.5 degrees) between the
      automated scheme and the human observer. It is concluded that the developed
      scheme would be suitable for online geometric verification of radiation therapy
      treatments.

PMID- 9659136
TI  - Evaluation of peripheral dual energy X-ray absorptiometry: comparison with single
      photon absorptiometry of the forearm and dual energy X-ray absorptiometry of the
      spine or femur.
AB  - An evaluation of the Osteoscan peripheral dual energy X-ray absorptiometer (pDXA)
      was carried out to compare its performance with those of a single photon
      absorptiometer (SPA) (Molsgaard Medical ND1100A) and a dual energy X-ray
      absorptiometer (DXA) (Lunar DPX alpha) of the spine or femur. In 57 patients,
      correlation between bone mineral content (BMC) of the forearm at the ultradistal
      (UD) site by pDXA and by SPA was high (r = 0.94). Comparisons were also made with
      spine and femur bone mineral density (BMD) DXA measurements. The correlation of z
      scores of UD BMD with z-scores for lumbar spine L2-L4 was r = 0.63 (n = 73
      patients); and with z-scores for neck of femur was r = 0.72 (n = 33). With the
      Osteoscan the measurement error coefficient of variation in vivo was 2.6% for
      BMC, 1.8% for BMD at the ultradistal site; 2.1% for BMC and 1.9% for BMD at the
      mid-distal site. Repeat measurements were made of the European forearm phantom;
      precision for SPA was slightly better than either pDXA or Lunar DXA. The
      Osteoscan has the potential for a rapid throughput of patients and is not
      affected by calcification and degenerative changes that can corrupt DXA
      measurements on the anteroposterior spine in older women.

PMID- 9659137
TI  - Enhancement of radiosensitivity of rat rhabdomyosarcoma R1H with normobaric
      carbogen and hyperbaric oxygen (HBO) using conventionally fractionated
      irradiation.
AB  - Hypoxic clonogenic cells are an important contributory factor in tumour
      radioresistance. The objective of the present study was to evaluate whether
      hyperbaric oxygen enhances tumour radiosensitivity, using a conventionally
      fractionated irradiation schedule, and whether the radiosensitizing potential is
      different from carbogen. Experiments were performed using the rhabdomyosarcoma
      R1H model transplanted subcutaneously in the flank of WAG/Rij rats. A total of 30
      X-ray fractions of 2 Gy were given either in air, normobaric carbogen or high
      pressure oxygen (HPO) (240 kPa, 2.37 atm) without anaesthesia. The time taken to
      achieve complete remission was 38.7 +/- 3.6 days, 36.7 +/- 2.7 days and 32.4 +/-
      4.1 days for air, normobaric carbogen and HBO, respectively. The differences
      between air and HBO (p = 0.002) and carbogen and HBO (p = 0.015) were
      significant. Use of carbogen and HBO produced the same local control probability
      at 150 days and this was significantly higher than local control under ambient
      conditions (p < 0.0001). It was concluded that the time to achieve complete
      remission of the rat rhabdomyosarcoma R1H can be shortened by HBO. Furthermore,
      both HBO and carbogen give higher local control probabilities than treatment
      under ambient conditions when used with a conventionally fractionated radiation
      schedule.

PMID- 9659138
TI  - Primary synovial sarcoma of the gastrocolic ligament.
AB  - A case of primary synovial sarcoma of the gastrocolic ligament is reported in a
      37-year-old woman. CT showed an encapsulated intraabdominal cystic tumour with an
      amorphous solid component. Barium studies showed a mass at the gastrocolic
      ligament which elevated the gastric antrum and displaced the transverse colon
      downwards. This is the first report of synovial sarcoma formation in the
      gastrocolic ligament. This tumour may have originated from pluripotential
      mesenchyme.

PMID- 9659139
TI  - Middle cranial fossa arachnoid cysts: not always a benign entity.
AB  - Arachnoid cysts are often discovered as incidental findings on cranial imaging. A
      rare manifestation is described in a child presenting acutely with symptoms and
      signs of raised intracranial pressure.

PMID- 9659140
TI  - MRI of a giant splenic artery aneurysm.
AB  - Aneurysms of the splenic artery larger than 3 cm are very rare. We present the
      imaging features of a 12 cm, partially thrombosed splenic artery aneurysm. MRI
      was valuable in establishing the diagnosis.

PMID- 9659141
TI  - The vanishing heart--deterioration on chest radiography with clinical improvement
      during prone position ventilation.
AB  - Prone position ventilation is used in the treatment of ARDS. Its beneficial
      effects are due to increased ventilation of the dorsal lung areas. Consequently,
      the now dependent parts of the lungs collapse, resulting in decreased sharpness
      of the cardiac silhouette. The latter may be misinterpreted as a worsening of the
      cardiopulmonary condition while, in fact, gas exchange and ventilation may be
      markedly improved. These features are illustrated in the case presented.

PMID- 9659142
TI  - Anatomical communications of the perirenal space.
AB  - There are controversies over the anatomical communications between the perirenal
      space and the adjacent extraperitoneal spaces. Clinical studies, mainly based on
      CT, show fluid collections extending into the adjacent space; into the bare area
      of the liver on the right, into the superior extraperitoneal space on the left,
      towards the midline from each perirenal space, and into the lower retroperitoneal
      space of the abdomen and pelvis. There are certain constant anatomical barriers
      limiting free extension of fluid or pathology. The pattern of fluid collection in
      the perirenal space and extension into the adjacent extraperitoneal space is
      relatively consistent although it varies with the amount and nature of the
      pathological fluid collection. This pictorial review illustrates anatomical
      barriers and CT findings of perirenal fluid collections and their extension into
      adjacent extraperitoneal spaces.

PMID- 9659143
TI  - Case of the month. In what's my line?

PMID- 9659144
TI  - Discharge of microcalcification during a localization procedure.

PMID- 9659145
TI  - Risk of childhood cancer from fetal irradiation.

PMID- 9659146
TI  - Reductions in fluoroscopy screening times resulting from physician credentialling
      and practice surveillance.

PMID- 9659147
TI  - The relationship between autoimmune markers and different clinical syndromes in
      autoimmune hepatitis.

PMID- 9659148
TI  - Just how inflamed is the normal gut?

PMID- 9659149
TI  - Intestinal metaplasia and the squamocolumnar junction: what does it all mean?

PMID- 9659150
TI  - Shock news for the gut.

PMID- 9659151
TI  - Altering cytokine soups: a recipe for inflammatory bowel disease?

PMID- 9659152
TI  - Chemokines in the gastric mucosa in Helicobacter pylori infection.
AB  - BACKGROUND: Although chemokines have been suggested to play an important role in
      Helicobacter pylori associated gastritis, few studies have investigated the role
      of chemokines other than interleukin 8 (IL-8) in gastric mucosa. AIMS: To
      investigate the expression and production patterns of various chemokines using
      gastric biopsy specimens. METHODS: In 192 patients, expression patterns of C-X-C
      chemokines (IL-8 and growth regulated alpha (GRO alpha)) and C-C chemokines
      (regulated on activation, normal T cell expressed and presumably secreted
      (RANTES), monocyte chemotactic and activating factor (MCAF), macrophage
      inflammatory protein 1 alpha (MIP-1 alpha), and MIP-1 beta) were examined using
      reverse transcription polymerase chain reaction (RT-PCR) and enzyme linked
      immunosorbent assay (ELISA). cagA gene was identified using PCR. RESULTS: H
      pylori infection was associated with increased rates of expression of mRNA for IL
      8, GRO alpha, RANTES, and MIP-1 alpha and with increased levels of mucosal IL-8
      and GRO alpha. IL-8 and GRO alpha levels correlated with the density of H pylori
      in both the antrum and corpus. The levels of these chemokines correlated with
      cellular infiltration in the antrum but not the corpus. cagA gene positive H
      pylori infection was associated with increased rates of expression of mRNA for IL
      8 and GRO alpha and with increased levels of these chemokines. CONCLUSION: H
      pylori infection is associated with increased expression rates and production of
      C-X-C chemokines (IL-8 and GRO alpha), but not with increased production of C-C
      chemokines. Although H pylori infection is associated with increased C-X-C
      chemokines in the antrum and corpus, there is a difference in the inflammatory
      response between these two areas of the stomach.

PMID- 9659153
TI  - Assessment of symptomatic response as predictor of Helicobacter pylori status
      following eradication therapy in patients with ulcer.
AB  - BACKGROUND: Helicobacter pylori eradication therapy is routinely used for
      treating patients with peptic ulcer disease. AIMS: To assess the value of
      symptomatic response to H pylori eradication therapy as a marker of post
      treatment H pylori status. PATIENTS AND METHODS: One hundred and nine dyspeptic
      patients with active duodenal or gastric ulceration association with H pylori
      infection had their symptoms measured by a validated questionnaire before and
      three months following H pylori eradication therapy. The symptomatic response was
      compared with post-treatment H pylori status as determined by the 14C urea breath
      test. RESULTS: An eradication rate of 84% was achieved. Of the 92 patients
      eradicated of H pylori, 47% experienced complete or near complete resolution of
      dyspepsia. Of the 17 patients in whom the infection was not eradicated, only one
      (6%) experienced resolution of dyspepsia. Resolution of dyspepsia was therefore a
      powerful predictor of eradication of H pylori with a predictive value of 98%. In
      contrast, persistence of dyspepsia was a weak predictor of persisting infection
      with a predictive value of only 25%. Excluding patients with endoscopic evidence
      of coexisting oesophagitis and/or retrosternal discomfort or reflux at initial
      presentation did not increase the predictive value of persisting dyspepsia for
      persisting infection. CONCLUSIONS: Complete resolution of dyspeptic symptoms is a
      powerful predictor of eradication of H pylori infection in ulcer patients.
      Persistence of symptoms is a weak predictor of persisting infection and patients
      with persisting dyspepsia must have their H pylori status rechecked to guide
      future management.

PMID- 9659154
TI  - Nitroxide radical attenuates ischaemia/reperfusion injury to the rat small
      intestine.
AB  - BACKGROUND: Free radicals are associated with post-ischaemic intestinal injury
      and contribute to major clinical problems primarily in premature infants. Various
      antioxidative means and modes of intervention, previously tested, have
      demonstrated only limited efficacy. AIMS: To study the protective activity of the
      stable nitroxide radical 4-OH, 2,2,6,6-tetramethylpiperidine-1-oxyl (TPL) and its
      respective hydroxylamine (TPL-H) against ischaemia/reperfusion (I/R) injury.
      METHODS: An isolated loop of ileum was created in laboratory male Sabra rats and
      constantly perfused with warmed normal saline. Intestinal injury was elicited
      through clamping of the superior mesenteric rat artery followed by reperfusion.
      Either TPL or TPL-H was given intravenously immediately before ischaemia or
      reperfusion and continuously afterwards. The rate of mucosal to lumen clearance
      of para-aminohippurate (PAH) was used to evaluate intestinal mucosal injury.
      Serum and perfusate levels of both TPL and TPL-H were measured using electron
      paramagnetic resonance spectrometry. RESULTS: The increase in intestinal
      permeability induced by I/R was significantly inhibited by both TPL and TPL-H.
      The nitroxide was effective also when given immediately before reperfusion.
      CONCLUSIONS: Through a continuous exchange, TPL and TPL-H act as self
      replenishing antioxidants and thus protect from intestinal injury. This
      demonstrates the potential of the family of nitroxide antioxidants against
      oxidative stress in general and I/R injury in particular.

PMID- 9659155
TI  - Medium-term effects of a new 5HT3 antagonist, alosetron, in patients with
      carcinoid diarrhoea.
AB  - BACKGROUND: Carcinoid diarrhoea is associated with rapid small bowel and proximal
      colonic transit. Intravenous administration of a serotonin type 3 receptor (5HT3)
      antagonist restores postprandial colonic tone towards normal in carcinoid
      patients. AIMS: To evaluate the medium-term effects of an oral 5HT3 antagonist,
      alosetron, on symptoms, stool fat, and transit in patients with carcinoid
      diarrhoea. METHODS: In 27 patients with carcinoid diarrhoea, symptoms were
      recorded daily and gastrointestinal transit was measured by scintigraphy in a
      three dose (0.1, 0.5, 2.0 mg, twice daily), randomised (1:1:1), parallel group,
      four week study. Placebo was given during the first week. Loperamide (2 mg
      capsules) was used as rescue medication. RESULTS: There were numerical
      improvements in median diarrhoea score, stool weight, loperamide use, and overall
      colonic transit at four hours, but no overall significant drug effect was shown.
      Alosetron reduced the proximal colon emptying rate (p < 0.05 in 20 evaluable
      comparisons), but did not significantly alter small bowel transit. CONCLUSIONS:
      Alosetron retardation of proximal colonic emptying in patients with carcinoid
      diarrhoea confirms the potential role of a 5HT3 mechanism in this disorder. Doses
      of alosetron higher than 2.0 mg twice daily will be required for symptomatic
      benefit in carcinoid diarrhoea.

PMID- 9659156
TI  - Cytokine profiles of cultured microvascular endothelial cells from the human
      intestine.
AB  - BACKGROUND AND AIMS: Cytokine production by endothelial cells, has, for practical
      reasons, been chiefly studied in human umbilical vein endothelial cells (HUVEC)
      but, because tissue-specific differences apparently exist, the role of human
      intestinal microvascular endothelial cells (HIMEC) as a source of mucosal
      cytokines was also assessed. METHODS: The expression of cytokine transcripts in
      HIMEC was screened by means of reverse transcription polymerase chain reaction
      (RT-PCR) and compared with cytokine profiles of HUVEC. Production of cytokines
      was investigated by bioassay and enzyme linked immunosorbent assay (ELISA).
      RESULTS: In the basal unstimulated state, HIMEC and HUVEC cultures contained
      detectable mRNA for interleukin (IL)-3, IL-7, IL-8, IL-11, IL-14, IL-15, tumour
      necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, and
      granulocytemacrophage colony stimulating factor (GM-CSF). However, message was
      undetectable for IL-2, IL-4, IL-5, IL-9, IL-10, IL-12p40, IL-13, and interferon
      (IFN)-gamma in the resting as well as the stimulated state. Stimulation of HIMEC
      and HUVEC with recombinant human (rh) IL-1 beta or rhTNF-alpha induced cell
      associated bioactive IL-1 alpha but not IL-1 beta, as well as enhanced secretion
      of both IL-6 and IL-8. Furthermore, transcript levels for GM-CSF and TNF-alpha
      were enhanced by rhIL-1 beta or rhTNF-alpha in both cell types. Supernatants from
      Th1-like or Th0-like gluten reactive intestinal T cell clones derived from
      patients with coeliac disease elicited cytokine profiles in both HIMEC and HUVEC
      similar to those revealed after rhIL-1 beta or rhTNF-alpha stimulation.
      CONCLUSIONS: These data demonstrate that the intestinal microvascular endothelium
      may contribute to the cytokine network of the intestinal mucosa with the ability
      to respond to locally generated cytokines and to produce potent inflammatory
      mediators.

PMID- 9659157
TI  - Spontaneous secretion of interferon gamma and interleukin 4 by human
      intraepithelial and lamina propria gut lymphocytes.
AB  - BACKGROUND: Cytokines secreted by intestinal T lymphocytes probably play a
      critical role in regulation of the gut associated immune responses. AIMS: To
      quantify interferon gamma (IFN-gamma) and interleukin 4 (IL-4) secreting cells
      (SC) among human intraepithelial (IEL) and lamina propria (LPL) lymphocytes from
      the duodenum and right colon in non-pathological situations and in the absence of
      in vitro stimulation. PATIENTS: Duodenal and right colonic biopsy specimens were
      obtained from patients with no inflammation of the intestinal mucosa. METHODS:
      Intraepithelial and lamina propria cell suspensions were assayed for numbers of
      cells spontaneously secreting IFN-gamma and IL-4 by a two site reverse enzyme
      linked immunospot technique (ELISPOT). RESULTS: The relatively high proportion of
      duodenal lymphocytes spontaneously secreting IFN-gamma (IEL 3.6%; LPL 1.9%) and
      IL-4 (IEL 1.3%; LPL 0.7%) contrasted with the very low numbers of spontaneously
      IFN-gamma SC and the absence of spontaneously IL-4 SC among peripheral blood
      mononuclear cells. In the basal state, both IFN-gamma and IL-4 were mainly
      produced by CD4+ cells. Within the colon, only 0.2% of IEL and LPL secreted IFN
      gamma in the basal state, and 0.1% secreted IL-4. CONCLUSIONS: Compared with
      peripheral lymphocytes substantial proportions of intestinal epithelial and
      lamina propria lymphocytes spontaneously secrete IFN-gamma and/or IL-4. These
      cytokines are probably involved in the normal homoeostasis of the human
      intestinal mucosa. Disturbances in their secretion could play a role in the
      pathogenesis of gastrointestinal diseases.

PMID- 9659158
TI  - Tumour necrosis factor-alpha enhances intraepithelial lymphocyte proliferation
      and migration.
AB  - BACKGROUND: Tumour necrosis factor alpha (TNF-alpha) is a proinflammatory
      cytokine found in abundance in diseased intestine. AIMS: The T cell production of
      TNF-alpha and the impact of this cytokine on intestinal T cell proliferation,
      migration, and cytotoxicity were studied. METHODS: Intestinal lymphocytes from
      normal jejunum were used. TNF-alpha production in culture supernates was measured
      by enzyme linked immunosorbent assay (ELISA). Lymphocyte proliferation was
      measured using 3H thymidine uptake; migration, using transwell chambers; and
      cytotoxicity of HT-29 colon cancer cells, using the chromium-51 release assay.
      RESULTS: TNF-alpha was produced mainly by the CD8+ T cells in the intraepithelial
      lymphocytes (IEL) and the CD4+ T cells in the lamina propria lymphocytes in
      response to CD2 stimulation: 478 (94) and 782 (136) pg/ml, respectively. TNF
      alpha (1 ng/ml or greater) augmented proliferation of IEL in response to
      interleukin 2 (IL-2), IL-7, or antibody to CD3 due to increased activation that
      did not involve IL-2 production or receptor generation. Conversely, antibody to
      TNF-alpha reduced IEL proliferation in response to IL-2 or IL-7. TNF-alpha also
      induced calcium mobilisation and chemokinesis (by 2.8 (0.5) fold over spontaneous
      migration). TNF-alpha had no effect on lymphokine activated killer cell activity.
      CONCLUSIONS: TNF-alpha increases the proliferation and migration of IEL, which
      may expand their number in the epithelium.

PMID- 9659159
TI  - Effects of smoking on the urine excretion of oral 51Cr EDTA in ulcerative
      colitis.
AB  - BACKGROUND: Smokers have a reduced risk and ex-smokers an increased risk of
      ulcerative colitis (UC). Stopping smoking often precedes onset and relapses.
      Smoking reduces the 24 hour urine excretion of oral chromium-51 labelled EDTA in
      healthy individuals. AIMS: To estimate the effects of smoking on the urine
      excretion of oral 51Cr EDTA in well characterised patients with UC. SUBJECTS:
      Sixteen smoking and 16 non-smoking patients with UC in remission were studied.
      The non-smokers had never smoked. Most were taking 5-aminosalicylic acid. No
      patient took steroids or immunosuppressants. The control group comprised 25
      smoking healthy volunteers and 25 who had never smoked. The median cigarette
      consumption was equal in the patients and volunteers. METHODS: The 24 hour urine
      excretion of oral 51Cr EDTA was measured and the results were correlated with
      smoking habits, number of cigarettes, and disease extent. RESULTS: Patients with
      UC had significantly higher 24 hour urine recoveries than healthy controls (p =
      0.04). This difference was more pronounced when patients who smoked were compared
      with healthy smokers (p = 0.005) No significant differences were found when
      comparing non-smoking patients with non-smoking controls or when comparing
      smoking and non-smoking patients. Urine recoveries did not correlate with number
      of cigarettes or disease extent. Smoking was more prevalent in patients with a
      more limited disease extent (p = 0.033). CONCLUSIONS: Effects of smoking on the
      urine excretion of 51Cr EDTA in health were abolished by the presence of UC. The
      protective effects of smoking in established UC are not due to a moderating
      effect of smoking on intestinal permeability.

PMID- 9659160
TI  - Short segments of Barrett's epithelium and intestinal metaplasia in normal
      appearing oesophagogastric junctions: the same or two different entities?
AB  - BACKGROUND: Endoscopic diagnosis of short segments of Barrett's epithelium
      (SSBE)' is difficult and its meaning in terms of the presence of specialised
      columnar epithelium (SCE) has not been prospectively evaluated. AIMS: To evaluate
      the prevalence of SCE in patients with an endoscopic diagnosis of SSBE and in
      individuals with normal appearing oesophagogastric junctions, and to compare the
      clinical characteristics of these two groups. PATIENTS: Thirty one patients with
      an endoscopic diagnosis of short Barrett's oesophagus, less than 3 cm in length
      (group A), and 44 consecutive patients with normal appearing oesophagogastric
      junctions (group B). METHODS: Multiple biopsies were performed in suspicious
      epithelium and at the oesophagogastric junction in groups A and B, respectively.
      RESULTS: Age and sex distribution were similar in both groups. Reflux symptoms
      were more frequent in group A (p < 0.001), as were endoscopic and histological
      signs of oesophagitis (p < 0.001 and p = 0.001, respectively). SCE was found in
      61.3% of group A patients compared with 25% in group B (p < 0.002), with men
      predominating in group A while women were more frequent in group B (p = 0.02).
      The differences in reflux symptoms and endoscopic/histological oesophagitis
      remained significant. CONCLUSIONS: These results show that endoscopic diagnosis
      of SSBE is associated with a high prevalence of SCE, significantly higher than
      that found in normal appearing oesophagogastric junctions. Differences between
      patients with SCE in the two groups suggest they may represent two different
      entities.

PMID- 9659161
TI  - Clonal analysis of isolated intestinal metaplastic glands of stomach using X
      linked polymorphism.
AB  - BACKGROUND: Monoclonal precancerous cells undergo successive biochemical and
      genetic changes during the multistep process of carcinogenesis in the
      gastrointestinal tract. Despite a high association with intestinal-type stomach
      cancer (differentiated adenocarcinoma of the stomach), the role of intestinal
      metaplasia is unclear in stomach carcinogenesis. AIMS: To study the clonality of
      intestinal metaplasia. METHODS: The clonality of 86 single intestinal metaplastic
      glands isolated by EDTA treatment from gastrectomy specimens from patients with
      cancer were investigated. The methylation sensitive restriction enzyme HpaII and
      polymerase chain reaction (PCR) were used to detect a polymorphic human androgen
      receptor gene locus linked to an inactive X chromosome. RESULTS: Forty one (48%)
      intestinal metaplastic glands were heterotypic (mixed cells of different allelic
      methylation) and 45 (52%) were homotypic (cell population of the same allelic
      methylation), while almost all the single pyloric glands were homotypic. Eleven
      of 13 intestinal metaplastic mucosae that were 6 mm in diameter contained glands
      that had originated from different cells. There were no strong relationships
      between clonal type and location or histological type of intestinal metaplasia.
      CONCLUSION: Intestinal metaplasia in general is not a lesion that arises or
      proceeds monoclonally.

PMID- 9659162
TI  - Somatic mutations, acetylator status, and prognosis in colorectal cancer.
AB  - BACKGROUND: Somatic mutations in K-ras and TP53 may be associated with both
      acetylator status and prognosis in colorectal cancer. AIMS: To determine whether
      cancers with somatic mutations are more frequent in fast acetylators and whether
      mutations or acetylator status influence prognosis after colorectal surgery.
      PATIENTS: One hundred consecutive subjects undergoing elective surgery for
      colorectal cancer. METHODS: Acetylator status was determined by polymerase chain
      reaction (PCR) genotyping for polymorphism in the N-acetyltransferase 2 (NAT2)
      gene. Mutations in K-ras (codon 12) and TP53 were determined by PCR analysis
      using restriction enzyme digestion and single strand conformation polymorphism
      respectively. Survival from colorectal cancer for up to five years after
      diagnosis was analysed using the Kaplan-Meier product limit estimator. Cox
      proportional hazards regression was used to compare survival rates after
      adjusting for tumour stage. RESULTS: Mutations in K-ras and TP53 were independent
      of acetylator status. By log rank test, survival was significantly reduced in
      subjects with TP53 mutations (p = 0.003) but was not significantly related to
      acetylator status or the presence of K-ras mutations. After adjustment for tumour
      stage, subjects with both TP53 and K-ras mutations had a 4.2-fold case fatality
      (95% confidence interval 1.5 to 11.6) when compared with that of a TP53 negative
      reference group. CONCLUSION: The presence of both TP53 and K-ras mutations in
      colorectal tumours is an adverse prognostic marker which is independent of tumour
      stage.

PMID- 9659163
TI  - Morphology of sporadic colorectal cancer with DNA replication errors.
AB  - BACKGROUND: Up to 15% of colorectal cancers are characterised by DNA
      microsatellite instability (MIN), shown by the presence of DNA replication errors
      (RERs). AIMS: To identify pathological features that are discriminating for
      colorectal cancer (CRC) showing extensive MIN. SUBJECTS: A prospective series of
      303 patients with CRC and no family history of either familial adenomatous
      polyposis or hereditary non-polyposis colorectal cancer. METHODS: DNA was
      extracted from fresh tissue samples and the presence of MIN was studied at nine
      loci that included TGF beta RII, IGFIIR, and BAX. The 61 cases showing RERs were
      compared with 63 RER negative cases with respect to a comprehensive set of
      clinical and pathological variables. Predictive utility of the variables was
      tested by decision tree analysis. RESULTS: Twenty seven patients with CRC showed
      extensive RERs (three loci or more) (RER+) and 34 had limited RERs only (28 = one
      locus; 6 = two loci) (RER+/-), yielding a bimodal distribution. RER+ cancers
      differed from RER- and RER+/-) cases. Tumour type (adenocarcinoma, mucinous
      carcinoma, and undifferentiated carcinoma) (p = 0.001), tumour infiltrating
      lymphocytes (p = 0.001), and anatomical site (p = 0.001) were the most
      significant of the discriminating variables. Algorithms developed by decision
      tree analysis allowed cases to be assigned to RER+ versus RER- and +/- status
      with a global sensitivity of 81.5%, specificity of 96%, and overall accuracy of
      93%. CONCLUSIONS: Pathological examination of CRC allows assignment of RER+
      status; assignment is specific and relatively sensitive. Conversely RER- and
      RER+/- CRC are indistinguishable.

PMID- 9659164
TI  - Infrequent K-ras codon 12 mutation in serrated adenomas of human colorectum.
AB  - BACKGROUND: Serrated adenoma is a new morphological subtype of colorectal
      adenoma. The lesion provides a distinct morphological route to carcinoma, but the
      underlying genetic changes have not yet been investigated. AIMS: To determine the
      frequency of K-ras mutation in serrated adenoma. METHODS: The frequency of K-ras
      codon 12 point mutation in 20 serrated adenomas, five atypical hyperplastic
      polyps, and 58 sporadic polypoid adenomas was investigated by nested polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods.
      RESULTS: Although most of the serrated adenomas were large (average size 11.4 mm)
      and polypoid, K-ras codon 12 point mutation was detected in only one of the 20
      (5%), which is a significantly lower frequency than that in sporadic polypoid
      adenomas (18/60; 30%) (p = 0.017). No mutation was detected in the atypical
      hyperplastic polyps. Three of 20 (15%) serrated adenomas contained a focus of
      carcinoma in situ, indicating their malignant potential and the existence of a
      serrated adenoma-carcinoma sequence, but no mutation was detected in the foci of
      carcinoma in situ. CONCLUSIONS: K-ras mutation is uncommon in serrated adenomas,
      indicating a different spectrum of genetic alterations in these lesions from
      those in typical polypoid sporadic adenomas. This subtype of colorectal adenoma
      represents a new genetic pathway in the histogenesis of colorectal carcinoma.

PMID- 9659165
TI  - Small bowel transit of a bran meal residue in humans: sieving of solids from
      liquids and response to feeding.
AB  - BACKGROUND: Ileal motor patterns are adapted to the propulsion of viscous meal
      residue, such as bran, which accumulates in the distal ileum postprandially.
      AIMS: To examine the effects of a second liquid/solid meal on ileal emptying.
      SUBJECTS AND METHODS: Eleven healthy fasting subjects consumed a 1.47 MJ pancake
      containing 15 g bran and 5 MBq Technetium-99m labelled amberlite resin (meal A).
      Gastric emptying and transit through the left upper quadrant (proximal) and right
      lower quadrant (distal) small bowel regions and colon were assessed
      scintigraphically. Transit was compared with and without a second Indium-111
      liquid/solid DTPA labelled 2.28 MJ meal (B) given three hours after the first
      meal. RESULTS: Gastric emptying of meal A was slower than meal B (the time for
      50% of the activity to leave the stomach (T50) being 113 (11) minutes versus 48
      (3) minutes respectively, p < 0.01, n = 11). Both meals passed rapidly through
      the proximal small bowel (T50 meal A = 57 (14) minutes versus T50 meal B = 42
      (11) minutes). Transit of meal A through the distal small bowel was much slower
      (T50 more than 390 minutes versus 176 (29) minutes for meal B, p < 0.01),
      resulting in meal B overtaking meal A and entering the colon earlier. Ingestion
      of the second meal (B) resulted in significantly less meal A marker entering the
      colon (5 (3)%) at 11 hours than when meal A was taken alone (18 (4)%) (p < 0.05,
      n = 8). CONCLUSIONS: The distal small bowel selectively retains bran, allowing
      liquid phase markers through to the colon. Consuming a second liquid/solid meal
      does not stimulate ileal transit of bran which seems to be propelled quicker by
      fasting motor patterns.

PMID- 9659166
TI  - Identification of distinct upper and lower gastrointestinal symptom groupings in
      an urban population.
AB  - BACKGROUND: The current classification dividing patients with functional
      gastrointestinal symptoms into subgroups remains controversial. AIMS: To
      determine whether distinct symptom groupings exist in the community. METHODS: A
      random sample of Sydney residents in Penrith, Australia was mailed a validated
      self report questionnaire. Gastrointestinal symptoms including the Rome criteria
      for irritable bowel syndrome (IBS) and dyspepsia were measured. RESULTS: Among
      730 respondents, the 12 month age and gender adjusted prevalence (adjusted to the
      Australian population) of IBS, dyspepsia, and gastro-oesophageal reflux were
      11.8% (95% confidence interval (CI) 9.3 to 14.3%), 11.5% (95% CI 9.6 to 14.6%),
      and 17.5% (95% CI 14.2 to 19.9%), respectively. In total, 60% of the population
      reported four or more gastrointestinal symptoms. There was considerable overlap
      of IBS with dyspepsia and among the dyspepsia subgroups by application of the
      Rome criteria. Independently, 10 symptom groupings were identified by factor
      analysis. The underlying constructs measured by these factors were generally the
      major abdominal syndromes recognised by the Rome classification: dyspepsia, IBS,
      reflux, painless constipation, painless diarrhoea, and bloating, in addition to a
      number of more specific symptom groupings. CONCLUSION: Gastrointestinal symptoms
      are common and overlap in the community, but distinct upper and lower abdominal
      symptom groupings can be identified.

PMID- 9659167
TI  - The endothelin receptor antagonist bosentan restores gut oxygen delivery and
      reverses intestinal mucosal acidosis in porcine endotoxin shock.
AB  - BACKGROUND: Endothelin-1, the most potent vasoconstrictor known, is produced in
      septic states and may be involved in the pathophysiology of the deteriorated
      splanchnic circulation seen in septic shock. AIMS: To elucidate the capability of
      bosentan, a non-peptide mixed endothelin receptor antagonist, to attenuate
      splanchnic blood flow disturbances and counteract intestinal mucosal acidosis in
      endotoxic shock. METHODS: In 16 anaesthetised pigs, central and regional
      haemodynamics were monitored by thermodilution and ultrasonic flow probes,
      respectively. A tonometer in the ileum was used for measurement of mucosal pH.
      Onset of endotoxin challenge was followed by bosentan administration (to eight
      pigs) two hours later. RESULTS: Endotoxin infusion reduced cardiac index and
      systemic oxygen delivery; bosentan restored these parameters. The reduced mean
      arterial blood pressure and renal blood flow remained unaffected by bosentan. The
      profound reduction in gut oxygen delivery in response to endotoxin was completely
      abolished by bosentan. Bosentan significantly improved the notably deteriorated
      intestinal mucosal pH and mucosal-arterial PCO2 gap. The mucosal-portal vein PCO2
      gap, used to monitor the mucosa in relation to the gut as a whole (including the
      spleen and pancreas), was also greatly increased by endotoxaemia and
      significantly reversed by bosentan. CONCLUSION: Bosentan completely restored the
      profound endotoxin induced reductions in systemic and gut oxygen delivery with a
      concomitant reversal of intestinal mucosal acidosis. Results suggest that
      endothelin is involved in the pronounced perfusion disturbances seen in the gut
      in endotoxic shock. Bosentan may prove useful in reducing gut ischaemia in septic
      shock.

PMID- 9659168
TI  - Management of occluded biliary Wallstents.
AB  - BACKGROUND: Wallstents (Schneider Stent, Inc., USA) used for the palliation of
      malignant biliary strictures, although associated with prolonged patency, can
      occlude. There is no consensus regarding the optimal management of Wallstent
      occlusion. AIMS: To evaluate the efficacy of different endoscopic methods for
      managing biliary Wallstent occlusion. METHODS: A multicentre retrospective study
      of patients managed for a biliary Wallstent occlusion. RESULTS: Data were
      available for 38 patients with 44 Wallstent occlusions, all of which had initial
      endoscopic management. Twenty four patients had died and 14 were alive after a
      median follow up of 231 (30-1095) days following Wallstent occlusion. Occlusions
      were managed by insertion of another Wallstent in 19, insertion of a plastic
      stent in 20, and mechanical cleaning in five. Endoscopic management was
      successful in 43 (98%). Following management of the occlusion, bilirubin
      decreased from 6.0 (0.5-34.3) to 2.1 (0.2-27.7) mg/100 ml (p < 0.05). No
      complications occurred. The median duration of second stent patency was 75 days
      (95% confidence interval 43 to 107) after insertion of another Wallstent, 90 days
      (71 to 109) after insertion of a plastic stent, and 34 days (30 to 38) after
      mechanical cleaning (NS). The respective median survivals were 70 days (22-118),
      98 days (54-142), and 34 days (30-380) (NS). Incremental cost effective analysis
      showed that plastic stent insertion is the most cost effective option.
      CONCLUSION: Although all three methods are equally effective in managing an
      occluded Wallstent, the most cost effective method appears to be plastic stent
      insertion.

PMID- 9659169
TI  - Is colonoscopic surveillance reducing colorectal cancer mortality in ulcerative
      colitis? A population based case control study.
AB  - BACKGROUND: Colonoscopic surveillance is a standard procedure in many patients
      with long standing, extensive ulcerative colitis (UC), in order to avoid death
      from colorectal cancer. No conclusive proof of its benefits has been presented
      however. AIMS: To evaluate the association between colonoscopic surveillance and
      colorectal cancer mortality in patients with UC. PATIENTS: A population based,
      nested case control study comprising 142 patients with a definite UC diagnosis,
      derived from a study population of 4664 patients with UC, was conducted. METHODS:
      Colonoscopic surveillance in all patients with UC who had died from colorectal
      cancer after 1975 was compared with that in controls matched for age, sex,
      extent, and duration of the disease. Information on colonoscopic surveillance was
      obtained from the medical records. RESULTS: Two of 40 patients with UC and 18 of
      102 controls had undergone at least one surveillance colonoscopy (relative risk
      (RR) 0.29, 95% confidence interval 0.06 to 1.31). Twelve controls but only one
      patient with UC had undergone two or more surveillance colonoscopies (RR 0.22,
      95% confidence interval 0.03 to 1.74), indicating a protective dose response
      relation. CONCLUSION: Colonoscopic surveillance may be associated with a
      decreased risk of death from colorectal cancer in patients with long standing UC.

PMID- 9659170
TI  - Evidence for altered hepatic matrix degradation in genetic haemochromatosis.
AB  - BACKGROUND: Altered matrix degradation contributes to fibrosis in some liver
      diseases but the role of matrix degradation in fibrogenesis associated with
      genetic haemochromatosis has not previously been addressed. AIMS: To measure
      serum concentrations of tissue inhibitor of metalloproteinase 1 (TIMP-1) and
      matrix metalloproteinases (MMP), MMP-1, MMP-2, and MMP-3 in patients with
      haemochromatosis and control subjects. PATIENTS: Forty patients with
      haemochromatosis and 19 healthy control subjects. Ten of the 40 patients were
      studied before and after venesection therapy. METHODS: Serum levels of TIMP-1,
      MMP-1, MMP-2, and MMP-3 were measured by enzyme immunoassay and correlated to
      hepatic iron concentration and degree of histological fibrosis. RESULTS: Serum
      TIMP-1 was increased in patients with haemochromatosis compared with controls
      (163 (30) versus 123 (28) ng/ml, p < 0.0002). Mean serum TIMP-1 concentration of
      patients with haemochromatosis without fibrosis was significantly higher than in
      controls (153 (16) versus 123 (28) ng/ml, p = 0.03). Serum TIMP-1 concentration
      correlated with both hepatic iron concentration and hepatic iron index (r = 0.42,
      p < 0.01; r = 0.42, p < 0.01). Serum MMP-2 concentrations correlated with
      increasing degree of fibrosis in patients with haemochromatosis (r = 0.38, p =
      0.01). The mean MMP-1: TIMP-1, MMP-2:TIMP-1 and age/sex matched MMP-3:TIMP-1
      ratios were significantly lower in patients with haemochromatosis than controls
      (0.11 (0.06) versus 0.2 (0.14), p = 0.02; 3.32 (0.9) versus 3.91 (0.81), p =
      0.05; and 0.26 (0.12) versus 0.47 (0.27), p = 0.007, respectively). Following
      venesection, MMP-2 and MMP-3 concentrations increased by 11% (p = 0.03) and 19%
      (p = 0.03), respectively. CONCLUSIONS: This study provides the first evidence of
      an alteration in matrix degradation in haemochromatosis that may be a
      contributing factor to hepatic fibrogenesis in this disease.

PMID- 9659171
TI  - Liver/kidney microsomal antibody type 1 and liver cytosol antibody type 1
      concentrations in type 2 autoimmune hepatitis.
AB  - BACKGROUND: Liver/kidney microsomal antibody type 1 (LKM1) and liver cytosol
      antibody type 1 (LC1) are the serological markers of type 2 autoimmune hepatitis
      (AIH). AIMS: Since LKM1 and LC1 react against two distinct liver specific
      autoantigens (cytochrome P450IID6 (CYP2D6) and a 58 kDa cytosolic polypeptide
      respectively), the aim was to see whether LKM1 and LC1 concentrations correlate
      with liver disease activity. PATIENTS: Twenty one patients with type 2 AIH were
      studied. METHODS: All sera were tested by indirect immunofluorescence,
      counterimmunoelectrophoresis, and immunoblotting visualised by enhanced
      chemiluminescence. To evaluate LKM1 and LC1 levels, the 50 kDa microsomal
      reactivity (corresponding to CYP2D6) and the 58 kDa cytosolic reactivity were
      quantified by densitometric analysis. RESULTS: Seven patients were positive for
      LKM1, nine for LC1, and five for both. Serial serum samples at onset and during
      immunosuppressive treatment were analysed in 13 patients (four positive for LKM1,
      six positive for LC1 and three positive for both). During remission, LKM1
      concentration remained essentially unchanged in six of seven patients, and
      decreased in only one. Conversely, in two of nine patients, LC1 was completely
      lost, and, in the remaining seven, LC1 concentration was reduced by more than
      50%. After immunosuppression tapering or withdrawal, flare ups of liver necrosis
      ensued with increasing LC1 concentration, but not LKM1. CONCLUSIONS: LC1
      concentration, at variance with that of LKM1, parallels liver disease activity,
      and its participation in the pathogenic mechanisms of liver injury can be
      hypothesised.

PMID- 9659172
TI  - The liver in systemic amyloidosis: insights from 123I serum amyloid P component
      scintigraphy in 484 patients.
AB  - BACKGROUND AND AIMS: The liver is frequently involved in amyloidosis but the
      significance of hepatic amyloid has not been systematically studied. We have
      previously developed scintigraphy with 123I serum amyloid P component (123I-SAP)
      to identify and monitor amyloid deposits quantitatively in vivo and we report
      here our findings in hepatic amyloidosis. METHODS: Between 1988 and 1995, 805
      patients with clinically suspected or biopsy proven systemic amyloidosis were
      evaluated. One hundred and thirty eight patients had AA amyloidosis, 180 had AL
      amyloidosis, 99 had hereditary amyloid syndromes, and 67 had dialysis related
      (beta 2 microglobulin) amyloid. One hundred and ninety two patients with
      amyloidosis were followed for six months to eight years. RESULTS: Hepatic amyloid
      was found in 98/180 (54%) AL and 25/138 (18%) AA patients but in only 1/53
      patients with familial transthyretin amyloid polyneuropathy and in none with
      dialysis related amyloidosis. There was complete concordance between hepatic SAP
      scintigraphy and the presence or absence of parenchymal amyloid deposits on liver
      histology. Amyloidosis was never confined to the liver. Mortality was rarely due
      to hepatic failure, although hepatic involvement with AA amyloid carried a poor
      prognosis. Successful therapy to reduce the supply of amyloid fibril protein
      precursors was followed by substantial regression of all types of amyloid.
      CONCLUSIONS: SAP scintigraphy is a specific and sensitive method for detecting
      and monitoring hepatic amyloid. Liver involvement is always associated with major
      amyloid in other organ systems and carries a poor prognosis in AA type.
      Appropriate therapy may substantially improve prognosis in many patients.

PMID- 9659173
TI  - In vivo and in vitro hepatic phosphorus-31 magnetic resonance spectroscopy and
      electron microscopy in chronic ductopenic rejection of human liver allografts.
AB  - BACKGROUND: In vivo hepatic phosphorus-31 magnetic resonance spectroscopy (MRS)
      provides non-invasive information about phospholipid metabolism. AIMS: To
      delineate MRS abnormalities in patients with chronic ductopenic rejection (CDR)
      and to characterise spectral changes by in vitro MRS and electron microscopy.
      PATIENTS AND METHODS: Sixteen liver transplant recipients (four with CDR; 12 with
      good graft function) and 29 controls (23 healthy volunteers; six patients with
      biliary duct strictures) were studied with in vivo 31P MRS. Peak area ratios of
      phosphomonoesters (PME) and phosphodiesters (PDE), relative to nucleotide
      triphosphates (NTP) were measured. In vitro MRS and electron microscopy were
      performed on biopsy specimens from five patients with CDR, freeze clamped at
      retransplantation. Phosphoethanolamine (PE), phosphocholine (PC),
      glycerophosphorylethanolamine (GPE), and glycerophosphorylcholine (GPC)
      concentrations were measured. RESULTS: The 12 patients with good graft function
      displayed no spectral abnormalities in vivo; the four patients with CDR showed
      significantly elevated PME:NTP (p < 0.01) and PDE:NTP ratios (p < 0.005).
      Patients with biliary strictures had significant differences in PME:NTP (p <
      0.01) from patients with CDR, but not in mean PDE:NTP. In vitro spectra from CDR
      patients showed elevated PE and PC, mirroring the in vivo changes in PME, but
      reduced GPE and GPC concentrations were observed, at variance with the in vivo
      PDE findings. On electron microscopy, there was no proliferation in hepatocyte
      endoplasmic reticulum. CONCLUSIONS: The increase in PME:NTP reflects altered
      phospholipid metabolism in patients with CDR, while the increase in PDE:NTP may
      represent a significant contribution from bile phospholipid.

PMID- 9659174
TI  - Outcome of orthotopic liver transplantation in patients with haemophilia.
AB  - BACKGROUND: Many patients with haemophilia have developed cirrhosis or
      hepatocellular carcinoma due to transfusion acquired chronic viral hepatitis.
      AIMS: To assess the long term outcome of all haemophilic patients reported to
      have undergone orthotopic liver transplantation. METHODS: Transplant centres of
      patients identified by medical database search were contacted and survival data
      assessed by Kaplan-Meier analysis. RESULTS: Twenty six haemophilic men (median
      age 46 years, range 5-63 years) underwent orthotopic liver transplantation in 16
      centres between 1982 and 1996. Indications for transplantation were hepatitis C
      cirrhosis (69%), hepatitis B with or without C cirrhosis (15%), viral hepatitis
      related hepatocellular carcinoma (12%), and biliary atresia (4%). Six patients
      (23%) were infected with human immunodeficiency virus (HIV). Postoperatively, the
      median time to normal clotting factor levels was 24 hours (range 0-48 hours) and
      exogenous clotting factors were stopped at a median of 24 hours (range 0-480
      hours). Four patients (15%) had bleeding complications. The one and three year
      survival of HIV positive recipients (67% and 23%) was significantly poorer (p =
      0.0003) than that of HIV negative recipients (90% and 83%). Coagulopathy was
      cured in all patients surviving more than 12 days post-transplant. Six of the 20
      patients (30%) with hepatitis C cirrhosis pretransplant had evidence of disease
      recurrence at a mean of nine months post-transplant. CONCLUSIONS: Hepatitis C
      cirrhosis is the most common indication for orthotopic liver transplantation in
      patients with haemophilia. Transplantation results in long term cure of
      haemophilia but may be complicated by the effects of HIV infection or recurrent
      viral hepatitis.

PMID- 9659175
TI  - Tranexamic acid for severe bleeding gastric antral vascular ectasia in cirrhosis.
AB  - BACKGROUND: It is believed that severe portal hypertensive gastropathy probably
      accounts for most non-variceal bleeding episodes in patients with cirrhosis.
      Gastric antral vascular ectasia (GAVE) also occurs in these patients. It is not
      clear whether it is a variant of portal hypertensive gastropathy or a distinct
      condition. PATIENT: A patient, a 66 year od woman, with cirrhosis initially
      diagnosed as having portal hypertensive gastropathy and subsequently classified
      as GAVE is described. She required transfusion with a total of 130 units of
      packed red cells for gastrointestinal blood loss. RESULTS: The bleeding did not
      respond to portal decompression with TIPS or beta blockers. Following treatment
      with oral tranexamic acid she has not required further blood transfusion over a
      period of 30 months. CONCLUSION: Tranexamic acid may be a useful treatment for
      refractory bleeding due to gastric antral vascular ectasia in patients with
      cirrhosis.

PMID- 9659176
TI  - Autoantibodies against subunits of pyruvate dehydrogenase and citrate synthase in
      a case of paediatric biliary cirrhosis.
AB  - In a newborn girl with a history of connatal liver damage, histological
      examination of a liver biopsy sample taken during the seventh week of life
      revealed incipient destruction of bile ducts. Very high titres of
      antimitochondrial antibodies were later detected in the plasma. As the hepatic
      injury tended towards fibrosis, the histological diagnosis became primary biliary
      cirrhosis. Autoantibodies against E1 alpha, E2, and E3 subunits and protein X
      component of pyruvate dehydrogenase complex, and against citrate synthase were
      detected on western immunoblotting in a 1 in 1000 dilution of the patient's
      serum. The patient died of her illness at 11 years of age. In liver specimens
      obtained at autopsy human immunoglobulin deposition was detected on the surface
      of almost all hepatic cells by immunohistology. As there is a physical and
      functional interaction between pyruvate dehydrogenase and citrate synthase within
      the mitochondria, the presence of autoantibodies against certain proteins in the
      patient suggests that in this form of the disease the molecular recognition and
      then the autoimmunisation process could be directed against a mitochondrial
      enzyme cluster containing both pyruvate dehydrogenase and citrate synthase.

PMID- 9659177
TI  - The aging stomach.

PMID- 9659178
TI  - Helicobacter pylori: beware "blind" eradication!

PMID- 9659179
TI  - Are complications of endoscopic sphincterotomy age related?

PMID- 9659180
TI  - History of dyspepsia in patients with gastric cancer.

PMID- 9659181
TI  - The genetics of ulcerative colitis based on one Swede.

PMID- 9659182
TI  - Iron reduction therapy in hepatitis C.

PMID- 9659183
TI  - Grading of cardiac transplant rejection.

PMID- 9659184
TI  - Cardiac output in 1998.

PMID- 9659185
TI  - Hypertension.

PMID- 9659186
TI  - Cell adhesion molecules in cardiovascular disease: a clinical perspective.
AB  - In summary, there is increasing evidence that cell adhesion molecules play an
      important role in cardiovascular pathology. They are involved in the main
      processes that underlie cardiac disease including thrombosis, leucocyte
      infiltration, smooth muscle proliferation, and cell migration. Anti-integrin
      treatment is already widely used to treat thrombotic complications, and it seems
      likely that manipulation of other cell adhesion molecules will be used clinically
      in the near future.

PMID- 9659187
TI  - Revision of the 1990 working formulation for cardiac allograft rejection: the
      Sheffield experience.
AB  - OBJECTIVE: To audit the 1990 International Society for Heart and Lung
      Transplantation cardiac rejection criteria and to evaluate the impact on
      classification and clinical outcomes of a modification in which grade 2 is
      abolished and grades 1A and 1B are amalgamated into a single "grade 1." METHODS:
      1652 heart biopsies were reviewed over a four year period. The initial 1348
      biopsies (group 1), using the original 1990 criteria, were analysed in terms of
      diagnostic grade and compared with the 304 biopsies analysed with the modified
      scheme (group 2). Differences in grading with the 1990 scheme were compared
      between two groups (1.1 and 1.2) reflecting early and late experience with
      grading. Subsequently all the grade 2 and grade 1B biopsies were rescored in
      terms of the modified scheme. Clinical results in terms of actuarial patient
      survival at one year and freedom from 3A rejection were similarly audited.
      RESULTS: The relative ratios of potentially significant rejection (grade 3A, 3B,
      4) remained constant over the entire study in groups 1.1, 1.2, and 2. A 50%
      reduction in grade 2 biopsy reporting was noted comparing early and late parts of
      group 1. At subsequent review of the group 1 grade 2 biopsies, 97% could be
      reassigned to grades 0 or 1 in the modified scheme, with the majority of these
      diagnoses reflecting Quility effect/biopsy site reactions. Two cases (3%) of the
      77 grade 2 biopsies were regraded as grade 3A rejection, with both occurring
      within three months of transplantation. None of the grade 1B biopsies had high
      grade cardiac rejection on review, most of these biopsies similarly showing
      pronounced Quility effect and biopsy site reactions. Actuarial survival at one
      year rose from 86% to 90% during the study, with freedom from 3A rejection
      remaining unchanged at 80%. CONCLUSIONS: The original working formulation
      produces consistent grading except at grade 2, which is judged to be a misnomer
      resulting from Quility effect and other non-rejection phenomena. While acceptable
      standardisation can be achieved with the 1990 scheme, the modified scheme has
      advantages in that it appears to encourage clear discrimination between
      significant and non-significant cardiac rejection. Overall, elimination of grade
      2 did not produce an increase in higher grades of cardiac rejection, and thus the
      value of this diagnostic grade is questioned.

PMID- 9659188
TI  - Comparison of impedance cardiography and dye dilution method for measuring
      cardiac output.
AB  - OBJECTIVE: To assess the degree of agreement between impedance cardiography,
      using the NCCOM3-R7 device, and the gold standard--the dye dilution method--both
      under basal conditions and after stimulation of cardiac output. PATIENTS: 35
      paired measurements in five healthy male volunteers. INTERVENTIONS: To obtain
      higher levels of cardiac output, cardiac performance was stimulated with a
      dopamine infusion. RESULTS: In 35 paired measurements, the mean of all the
      impedance values was higher than that of the dye dilution values, at 10.2 v 7.4
      l/min (p < 0.0001). The mean discrepancy between the two methods was 3.3 l/min,
      and the mean bias -2.9 l/min, with limits of agreement of -9.0 and 3.2 l/min. A
      change in cardiac output could not adequately be predicted by the NCCOM3-R7. In
      20 of 25 measurements obtained during continuous intravenous dopamine infusions
      there was a rise in dye dilution cardiac output (range 0.2 to 5.9 l/min). Neither
      the magnitude nor the direction of the change in dye dilution values corresponded
      with the change measured by impedance cardiography. The mean discrepancy here
      between the two methods was 1.8 l/min, and the mean bias -0.8 l/min, with limits
      of agreement of -4.9 and 3.3 l/min. CONCLUSIONS: In healthy volunteers, impedance
      cardiography with NCCOM3-R7 is inadequate for assessing cardiac output when
      compared with the dye dilution method.

PMID- 9659189
TI  - Hospital acquired native valve endocarditis: analysis of 22 cases presenting over
      11 years.
AB  - OBJECTIVE: To analyse hospital acquired infective endocarditis cases with respect
      to age, sex, clinical, laboratory, and echocardiographic features,
      predisposition, complications, surgery, mortality, and diagnostic criteria.
      DESIGN: Prospective cohort study. SETTING: Teaching hospital. PATIENTS: A series
      of 200 patients with infective endocarditis presenting over 11 years, 168 with
      native valve infective endocarditis, of whom 22 acquired this infection in
      hospital. RESULTS: 22 (14%) of the 168 cases of native valve infection were
      hospital acquired. The most common pathogens were staphylococci (77%). Two thirds
      of patients had no cardiac predisposition; one third had end stage renal disease.
      The most common source of infection was vascular access sites (73%). Eleven
      patients died. In 11 cases, infective endocarditis was proven pathologically (six
      at necropsy, five during surgery) and analysis of these showed that 45% were
      classed as probable by the Beth Israel criteria, 73% as definite by the Duke
      criteria, and 91% as definite by our suggested modifications of the Duke
      criteria. Figures for the 11 cases not proven pathologically were 27%, 73%, and
      91%, respectively. Five of the 22 cases (22%) were rejected by the Beth Israel
      criteria but none were rejected by the Duke criteria with or without our
      modifications. CONCLUSIONS: Hospital acquired infective endocarditis is difficult
      to diagnose. The Duke criteria have improved diagnostic sensitivity and our
      modifications have improved it further. Mortality is high but has been reduced by
      surgery. This serious infection could, in many cases, be prevented by improved
      care of intravascular lines and prompt removal when obviously infected.

PMID- 9659190
TI  - A prioritisation system for elective coronary angiography.
AB  - OBJECTIVE: To devise a clinical prioritisation system for rationing access to a
      cardiac catheter waiting list and to describe its performance at predicting
      angiographic findings and selecting patients for angioplasty or coronary artery
      bypass graft surgery. SETTING: Tertiary level cardiology centre. METHODS: (1) 665
      consecutive patients on an elective waiting list for coronary angiography were
      scored using a system derived from established clinical criteria for selecting
      patients for coronary surgery (New Zealand/Duke). The scores were compared with
      clinical outcome (referral for surgery, angioplasty, or medical management). (2)
      In a subset of 125 patients, scores derived from clinical criteria and exercise
      testing were compared with findings on coronary angiography. (3) Multivariate
      analysis was used in a new group of 178 patients to identify factors that would
      be better predictors of the angiographic score. (4) A new scoring system was
      devised based partly on the results of the multivariate analysis. It was applied
      to a new test group of 100 patients using clinical outcome and angiographic score
      as outcome measures. RESULTS: (1) Using the established clinical score, similar
      proportions of patients were referred after angiography for medical management,
      angioplasty, or coronary bypass grafting, irrespective of their original score.
      The exceptions were patients with a score < 20, who were more likely to continue
      medical management. (2) There was poor correlation (r = 0.05) between the
      clinical score and the subsequent angiographic score. (3) Multivariate analysis
      identified age, male sex, previous myocardial infarction, high cholesterol, and
      diabetes as independent predictors of coronary score. (4) The modified scoring
      system, incorporating the predictors identified by multivariate analysis,
      performed better than the original scoring system in predicting coronary score
      when both were tested, but some patients had severe disease despite a low score.
      CONCLUSIONS: Patients can be ranked using clinical and non-invasive criteria, and
      a rationing system implemented on this basis. With prioritisation by noninvasive
      criteria, the risk of missing serious coronary disease in patients with
      relatively mild symptoms must be accepted; this risk becomes greater the more
      stringently rationing is applied.

PMID- 9659191
TI  - Effects of alpha tocopherol and beta carotene supplements on symptoms,
      progression, and prognosis of angina pectoris.
AB  - OBJECTIVE: To evaluate the effects of alpha tocopherol and beta carotene
      supplements on recurrence and progression of angina symptoms, and incidence of
      major coronary events in men with angina pectoris. DESIGN: Placebo controlled
      clinical trial. SETTING: The Finnish alpha tocopherol beta carotene cancer
      prevention study primarily undertaken to examine the effects of alpha tocopherol
      and beta carotene on cancer. SUBJECTS: Male smokers aged 50-69 years who had
      angina pectoris in the Rose chest pain questionnaire at baseline (n = 1795).
      INTERVENTIONS: alpha tocopherol (vitamin E) 50 mg/day, beta carotene 20 mg/day or
      both, or placebo in 2 x 2 factorial design. MAIN OUTCOME MEASURES: Recurrence of
      angina pectoris at annual follow up visits when the questionnaire was
      readministered; progression from mild to severe angina; incidence of major
      coronary events (non-fatal myocardial infarction and fatal coronary heart
      disease). RESULTS: There were 2513 recurrences of angina pectoris during follow
      up (median 4 years). Compared to placebo, the odds ratios for recurrence in the
      active treatment groups were: alpha tocopherol only 1.06 (95% confidence interval
      (CI) 0.85 to 1.33), alpha tocopherol and beta carotene 1.02 (0.82 to 1.27), beta
      carotene only 1.06 (0.84 to 1.33). There were no significant differences in
      progression to severe angina among the groups given supplements or placebo.
      Altogether 314 major coronary events were observed during follow up (median 5.5
      years) and the risk for them did not differ significantly among the groups given
      supplements or placebo. CONCLUSIONS: There was no evidence of beneficial effects
      for alpha tocopherol or beta carotene supplements in male smokers with angina
      pectoris, indicating no basis for therapeutic or preventive use of these agents
      in such patients.

PMID- 9659192
TI  - Characterisation of coronary atherosclerotic morphology by spectral analysis of
      radiofrequency signal: in vitro intravascular ultrasound study with histological
      and radiological validation.
AB  - OBJECTIVE: To determine whether spectral analysis of unprocessed radiofrequency
      (RF) signal offers advantages over standard videodensitometric analysis in
      identifying the morphology of coronary atherosclerotic plaques. METHODS: 97
      regions of interest (ROI) were imaged at 30 MHz from postmortem, pressure
      perfused (80 mm Hg) coronary arteries in saline baths. RF data were digitised at
      250 MHz. Two different sizes of ROI were identified from scan converted images,
      and relative amplitudes of different frequency components were analysed from raw
      data. Normalised spectra was used to calculate spectral slope (dB/MHz), y-axis
      intercept (dB), mean power (dB), and maximum power (dB) over a given bandwidth
      (17-42 MHz). RF images were constructed and compared with comparative histology
      derived from microscopy and radiological techniques in three dimensions. RESULTS:
      Mean power was similar from dense fibrotic tissue and heavy calcium, but spectral
      slope was steeper in heavy calcium (-0.45 (0.1)) than in dense fibrotic tissue (
      0.31 (0.1)), and maximum power was higher for heavy calcium (-7.7 (2.0)) than for
      dense fibrotic tissue (-10.2 (3.9)). Maximum power was significantly higher in
      heavy calcium (-7.7 (2.0) dB) and dense fibrotic tissue (-10.2 (3.9) dB) than in
      microcalcification (-13.9 (3.8) dB). Y-axis intercept was higher in
      microcalcification (-5.8 (1.1) dB) than in moderately fibrotic tissue (-11.9
      (2.0) dB). Moderate and dense fibrotic tissue were discriminated with mean power:
      moderate -20.2 (1.1) dB, dense -14.7 (3.7) dB; and y-axis intercept: moderate 
      11.9 (2.0) dB, dense -5.5 (5.4) dB. Different densities of fibrosis, loose,
      moderate, and dense, were discriminated with both y-axis intercept, spectral
      slope, and mean power. Lipid could be differentiated from other types of plaque
      tissue on the basis of spectral slope, lipid -0.17 (0.08). Also y-axis intercept
      from lipid (-17.6 (3.9)) differed significantly from moderately fibrotic tissue,
      dense fibrotic tissue, microcalcification, and heavy calcium. No significant
      differences in any of the measured parameters were seen between the results
      obtained from small and large ROIs. CONCLUSION: Frequency based spectral analysis
      of unprocessed ultrasound signal may lead to accurate identification of
      atherosclerotic plaque morphology.

PMID- 9659193
TI  - Abnormal ventricular activation and repolarisation during dobutamine stress
      echocardiography in coronary artery disease.
AB  - OBJECTIVE: To assess possible ECG changes caused by dobutamine stress and their
      relation to wall motion disturbances in patients with coronary artery disease.
      DESIGN: Prospective recording and analysis of 12 lead ECG at rest and during each
      stage of dobutamine stress echocardiography, and correlation with wall motion
      changes. SETTING: A tertiary referral centre for cardiac disease equipped with
      non-invasive facilities for pharmacological stress tests. SUBJECTS: 27 patients,
      mean (SD) age 60 (8) years, with documented evidence of coronary artery disease
      in whom dobutamine stress echo was clinically indicated, and 17 controls of
      similar age. RESULTS: In controls, all ECG intervals shortened with increasing
      heart rate but in the patient group only PR and QT intervals shortened while QRS
      duration broadened and QTc interval prolonged progressively. In the 27 patients,
      16 developed chest pain, 15 with reduced left ventricular long axis systolic
      excursion (p < 0.001), and all showed reduced peak lengthening rate; ST segment
      shift appeared in 16, 13 of whom developed chest pain, but did not correlate with
      reduction of either systolic long axis excursion or peak lengthening rate; QRS
      duration broadened in 20, 16 with reduction of long axis excursion (p < 0.02)
      which was more often seen at the septum (p < 0.005); QTc interval prolonged in
      19, all of whom had associated reduction of peak long axis lengthening rate (p <
      0.02). CONCLUSIONS: QRS duration and QTc interval both normally shorten with
      dobutamine stress, while in coronary artery disease they both lengthen: changes
      in QRS duration correlate with systolic and QTc interval with diastolic left
      ventricular wall motion disturbances. ST segment shift also occurred in most
      patients, but without consistent correlation with wall motion abnormalities. It
      was thus less discriminating than the other two abnormalities in this respect.

PMID- 9659194
TI  - Enhanced dispersion of epicardial activation-recovery intervals at sites of
      histological inhomogeneity during regional cardiac ischaemia and reperfusion.
AB  - OBJECTIVE: To examine how epicardial activation and repolarisation patterns
      change in the course of ischaemia, and how these changes are related to the
      underlying histological structures. METHODS: Langendorff perfused isolated rabbit
      hearts were submitted to 30 minutes of left anterior descending coronary artery
      occlusion followed by 30 minutes of reperfusion. A 256 channel epicardial map was
      plotted during the various experimental phases. Activation time points were
      determined as t(dU/dtmin) and repolarisation time points as t(dU/dtmax). From
      these data the local activation-recovery interval (ARI), its dispersion (SD of
      ARI), and the geometry of the activation spread could be analysed. After the
      experiments the hearts were processed histologically and the mapping data were
      projected onto histological slides. RESULTS: There was elevation of the ST
      segment within the occluded area, which recovered during reperfusion. Within this
      area, ARI was significantly shortened and its dispersion was maximally enhanced.
      The enhancement of dispersion was pronounced at sites of histological
      inhomogeneity like fat, connective tissue, or vessels. There was also a change in
      the preferential direction of activation spread within the occluded zone with a
      marked transverse propagation of the activation wave-front, whereas under normal
      conditions the activation followed the longitudinal fibre axis. In addition, the
      total activation time in the occluded area was significantly prolonged.
      CONCLUSIONS: Ischaemia alters the local activation pattern with enhanced
      dispersion, especially at sites of histological irregularity, transverse shift of
      the activation waves, and a general slowing of conduction, which may explain the
      increased susceptibility to arrhythmia in hearts with enhanced histological
      irregularities--for example, an infarct or in multi-infarcted hearts, or after
      myocarditis.

PMID- 9659195
TI  - Does restrictive right ventricular physiology in the early postoperative period
      predict subsequent right ventricular restriction after repair of tetralogy of
      Fallot?
AB  - OBJECTIVE: To assess the relation between immediate postoperative right
      ventricular (RV) diastolic physiology and subsequent diastolic function in
      patients after repair of tetralogy of Fallot. DESIGN: Serial prospective
      echocardiographic study early after surgical repair of tetralogy of Fallot and at
      mid-term follow up. SETTING: Tertiary referral centre. PATIENTS: 34 patients who
      had repair of tetralogy of Fallot between 1992 and 1995 were studied. MAIN
      OUTCOME MEASURES: Restrictive RV physiology defined as antegrade flow in the
      pulmonary artery in late diastole throughout the respiratory cycle. RESULTS:
      Sixteen of the 34 patients had early restrictive RV physiology. The need for
      transannular patch repair was an independent variable predictive of early
      restriction (odds ratio 4.3 (1.1-47), p < 0.05). Nine of 16 patients with early
      restriction also had restriction at follow up, while 15 of 16 patients without
      restrictive RV physiology continued without restriction. Early restriction was
      the only independent variable predictive of late restriction (odds ratio 6.0 (1.9
      273), p = 0.01). CONCLUSIONS: Early and mid-term restrictive RV physiology after
      repair of tetralogy of Fallot is related to the repair type. Although evidence
      for this physiology tends to resolve in the first few days after operation, it is
      highly predictive of subsequent abnormalities of RV diastolic function.
      Similarly, normal RV diastolic physiology without restriction in the immediate
      postoperative period persists in the mid-term and may be associated with the long
      term problems of progressive RV dilatation.

PMID- 9659197
TI  - Neck pounding during sinus rhythm: a new clinical manifestation of dual
      atrioventricular nodal pathways.
AB  - OBJECTIVE: To determine the clinical and electrophysiological characteristics of
      patients with paroxysmal palpitations and neck pounding during sinus rhythm.
      METHODS: Clinical, electrocardiographic, and electrophysiological characteristics
      of six patients with paroxysmal palpitations and neck pounding during sinus
      rhythm were studied in basal conditions and when symptomatic. Response to
      treatment was observed. RESULTS: Baseline ECGs were normal (four patients) or had
      first degree atrioventricular block with intermittent PR shortening. During
      symptoms, narrow QRS rhythms were seen without visible P waves (three patients)
      or with P waves partially hidden in the QRS complex (three patients). Dual
      atrioventricular nodal pathways were found in all five patients who had
      electrophysiological studies. In these patients the slow pathway conduction time
      was long enough (mean (SD), 425 (121) ms) for ventricular activation after slow
      pathway conduction during sinus rhythm to coincide with the next atrial
      depolarisation, causing neck pounding during exercise (four patients) or at rest
      (two patients). Tachycardia was not induced in any patient. Medical treatment
      aggravated symptoms in three patients. A pacemaker was successfully used in two.
      CONCLUSIONS: Neck pounding during sinus rhythm is a clinical manifestation of
      dual atrioventricular nodal pathways. Medical treatment may aggravate symptoms
      but a pacemaker may offer definitive relief.

PMID- 9659196
TI  - Haemodynamic patterns in patients with scorpion envenomation.
AB  - OBJECTIVE: To study cardiovascular haemodynamics following scorpion envenomation.
      SETTING: Intensive care unit of a university hospital. PATIENTS: Eight patients
      with Indian red scorpion (Mesobuthus tamulus) stings. INTERVENTION: Captopril
      (6.25 to 12.5 mg orally) every 30 minutes until pulmonary oedema resolved. MAIN
      OUTCOME MEASURES: Haemodynamic data obtained by pulmonary artery catheterisation.
      RESULTS: Two haemodynamic patterns were seen. There was a predominant vascular
      effect in one patient, with severe hypertension, tachycardia, increased systemic
      vascular resistance index (SVRI = 5893 dyn.s.cm-5), and normal cardiac index
      (2.73 l/m2). A predominant myocardial effect with left ventricular dysfunction
      and normal right ventricular function was seen in the other seven patients, with
      tachycardia, pulmonary oedema, mild hypotension, reduced stroke volume (mean
      (SD), 25.9 (8.3) ml/m2), normal SVRI (1812 (831) dyn.s.cm-5), and increased
      pulmonary artery wedge pressure (PAWP = 25 (4.4) mm Hg). Following mild
      dehydration pulmonary oedema subsided (PAWP = 14 (8.5) mm Hg) in three of these
      patients, but hypovolaemic shock developed (right atrial pressure (RAP) = 1.3
      (2.1) mm Hg); pulmonary oedema recurred with rehydration. One patient developed
      fatal cardiogenic shock with raised PAWP (27 mm Hg) and RAP (11 mm Hg), and
      vasodilatation (SVRI = 1129 dyn.s.cm-5). Stroke volume (30.5 (8.7) ml/m2) and
      cardiac output (4.3 (1.5) 1/m2) improved with resolution of pulmonary oedema
      (PAWP = 14.4 (4.2) mm Hg) following afterload reduction with captopril.
      CONCLUSIONS: Mild envenomation causes severe vasoconstriction and hypertension.
      Severe envenomation produces predominant left ventricular dysfunction with normal
      systemic vascular resistance manifesting as pulmonary oedema or severe
      hypotension depending on the fluid balance. Shock due to biventricular
      dysfunction and vasodilatation occurs terminally.

PMID- 9659198
TI  - Circadian rhythm of the signal averaged electrocardiogram and its relation to
      heart rate variability in healthy subjects.
AB  - OBJECTIVE: To examine the circadian variation in the signal averaged
      electrocardiogram (saECG) and heart rate variability and investigate their
      relations in healthy subjects. METHODS: 24 hour ECGs were obtained with a three
      channel recorder using bipolar X, Y, and Z leads in 20 healthy subjects. The
      following variables were determined hourly: heart rate, filtered QRS (f-QRS)
      duration, low and high frequency components of heart rate variability (LF and
      HF), and the LF/HF ratio. RESULTS: Heart rate, f-QRS duration, HF, and the LF/HF
      ratio showed significant circadian rhythms, as determined by the single cosinor
      method. Heart rate and the LF/HF ratio increased during daytime, and f-QRS
      duration and HF increased at night. f-QRS duration was negatively correlated with
      heart rate (r = 0.95, p < 0.001) and the LF/HF ratio (r = 0.94, p < 0.001) and
      positively with HF (r = 0.93, p < 0.001). CONCLUSIONS: f-QRS duration has a
      significant circadian rhythm in healthy subjects and is closely related to the
      circadian rhythm of autonomic tone.

PMID- 9659199
TI  - Distribution of fast heart rate episodes during paroxysmal atrial fibrillation.
AB  - OBJECTIVE: To investigate the defibrillator waiting time (time between the
      recognition of atrial fibrillation and the actual shock) by studying paroxysmal
      atrial fibrillation episodes with RR intervals shorter than a certain limit (that
      is, episodes during which defibrillation should not be attempted). METHODS: Long
      term 24 hour Holter recordings from a digoxin v placebo crossover study in
      patients with paroxysmal atrial fibrillation were analysed. In all, 23 recordings
      with atrial fibrillation episodes of at least 1000 ventricular cycles and with <
      20% Holter artefacts or noise were used (11 recorded on placebo and 12 on
      digoxin). For each recording, the mean ("mean waiting time") and maximum
      ("maximum waiting time") duration of continuous sections of atrial fibrillation
      episodes with all RR intervals shorter than a certain threshold were evaluated,
      ranging the threshold from 400 to 1000 ms in 10 ms steps. For each threshold, the
      mean and maximum waiting times were compared between recordings on placebo and on
      digoxin. RESULTS: Both the mean and maximum waiting times increased exponentially
      with increasing threshold. Practically acceptable mean waiting times less than
      one minute were observed with thresholds below 600 ms. There were no significant
      differences in mean waiting times and maximum waiting times between recordings on
      placebo and digoxin, and only a trend towards shorter waiting times on digoxin.
      CONCLUSIONS: Introduction of a minimum RR interval threshold required to deliver
      atrial defibrillation leads to practically acceptable delays between atrial
      fibrillation recognition and the actual shock. These delays are not prolonged by
      digoxin treatment.

PMID- 9659200
TI  - Pseudoaneurysm of femoral artery after catheterisation: treatment by a mechanical
      compression device guided by colour Doppler ultrasound.
AB  - BACKGROUND: Femoral artery pseudoaneurysm is a significant complication in
      patients undergoing diagnostic or therapeutic catheterisation. First choice
      treatment for pseudoaneurysm is freehand ultrasound guided compression repair,
      which is time consuming and uncomfortable for the patient and operator. AIM: To
      explore a mechanical compression device (FemoStop) as an alternative treatment
      for iatrogenic femoral artery pseudoaneurysm. METHODS: Fourteen patients with
      pseudoaneurysm were considered for treatment with FemoStop after a brief freehand
      ultrasound guided compression repair to confirm the compressibility of the
      lesion. The FemoStop compression was applied for 20 minutes. The result was
      controlled with colour Doppler ultrasound, and a second cycle of 20 minutes
      followed if necessary. RESULTS: FemoStop compression was successful in 13 of the
      14 patients. The mean compression time was 33 minutes (range, 20-60). The mean
      number of compression periods was 1.6 (range 1-3). FemoStop compression was
      successful in all 11 patients not taking anticoagulants and in two of three
      patients receiving anticoagulants. The mean compression time in patients given
      oral or intravenous anticoagulants was longer (50 v 27 minutes). Colour Doppler
      ultrasound 12 hours after the procedure indicated no recurrence of pseudoaneurysm
      in the 13 patients with initial success. CONCLUSIONS: FemoStop compression for
      iatrogenic pseudoaneurysm is feasible, and as safe and effective as freehand
      ultrasound guided compression repair. It is more comfortable for the patient and
      operator, and probably more economical than freehand compression.

PMID- 9659201
TI  - Aneurysms and pseudoaneurysms of saphenous vein coronary artery bypass grafts.
AB  - Aneurysms of saphenous vein grafts to coronary arteries are unusual complications
      of coronary artery bypass graft (CABG) surgery. Three patients (men aged 47, 62,
      and 68 years) are presented with spontaneous chest pains 10, 21, and 17 years
      after CABG surgery. In one case, the saphenous vein graft had eroded into the
      right atrium and had established a fistula between the graft and the right
      atrium. Diagnosis of saphenous vein graft aneurysms was confirmed by
      echocardiography, computed tomography or magnetic resonance imaging, and by
      arteriography. Two patients were treated surgically, the third by percutaneous
      coil embolisation followed by balloon angioplasty of the right coronary artery.

PMID- 9659202
TI  - Reopening of persistent left superior caval vein after bidirectional
      cavopulmonary connections.
AB  - Persistent left superior vena cava (SVC) is a not uncommon finding in patients
      with congenital heart disease. This anatomical variant must be recognised before
      doing a Glenn anastomosis, bidirectional cavopulmonary connection or a Fontan
      type procedure. Following these procedures, reopening of a left SVC leading to
      clinical cyanosis can occur. Five cases are described in whom persisting left
      SVCs were excluded before performing a bidirectional cavopulmonary connection or
      Fontan procedure but (re-)opened after surgery, leading to cyanosis either by
      reducing effective pulmonary blood flow (bidirectional cavopulmonary connection)
      or by an obligatory right to left shunt (Fontan). These observations suggest
      that, embryologically, the lumen of the left SVC obliterates rather than
      disappears. Balloon occlusion angiography of the innominate vein before
      cavopulmonary connections or Fontan procedures might improve detection of these
      collateral vessels.

PMID- 9659203
TI  - Truncus arteriosus with anterior origin of a hypoplastic main pulmonary artery.
AB  - A newborn with an unusual form of truncus arteriosus is described, whose clinical
      presentation and certain features of her anatomy were more typical of pulmonary
      atresia with a ventricular septal defect. The morphological differentiation of
      certain types of truncus arteriosus and pulmonary atresia with ventricular septal
      defect remains an area of speculation among cardiac pathologists, and research in
      this area is being done using animal models. The anatomic features of the heart
      described in this report may assist in this discussion as the application of
      observations made in animal models to human cardiac development may be
      problematic.

PMID- 9659204
TI  - Images in cardiology. An isolated single coronary artery.

PMID- 9659205
TI  - Cavernous haemangioma in the coronary sinus.
AB  - A 58 year old man with a history of cerebral infarction was admitted to hospital
      with chest discomfort and dyspnoea. He had no history of precordial chest
      discomfort. Angiography and left ventriculography showed that coronary fistulas
      connected the coronary sinus with the left circumflex and right coronary
      arteries. His coronary sinus did not communicate with the right atrium, draining
      instead into a persistent left superior vena cava. Angiography showed a mass,
      suspected to be a thrombus, in the coronary sinus. Transoesophageal
      echocardiography confirmed the presence of a mass in the atrioventricular groove.
      The mass was removed at surgery and proved to be a cavernous haemangioma.

PMID- 9659206
TI  - Sotalol associated polymorphic ventricular tachycardia and coronary spasm.
AB  - Sotalol may induce torsade de pointes through cardiac action potential
      prolongation, but a proarrhythmic effect secondary to its beta blocking action
      has not been reported. A 54 year old man presented with symptoms of angina and
      presyncope, subsequently demonstrated to be associated with coronary spasm.
      Treatment with sotalol exacerbated his symptoms and resulted in recurrent
      polymorphic ventricular tachycardia with a pattern indistinguishable from that
      caused by a class III action. Following sotalol with-drawal polymorphic
      ventricular tachycardia resolved completely. Polymorphic ventricular tachycardia
      in patients treated with sotalol may therefore not always be the result of
      delayed repolarisation, but may be caused by beta adrenoceptor blockade.

PMID- 9659207
TI  - Anomalous left pulmonary artery without pulmonary artery sling.

PMID- 9659208
TI  - Atrioventricular fistula: an unusual complication of a ventricular pseudoaneurysm
      after myocardial infarction.

PMID- 9659209
TI  - An unusual intracardiac shunt secondary to penetrating cardiac trauma.

PMID- 9659210
TI  - Cardiogenic refractory hypoxaemia secondary to blunt chest trauma: diagnosis by
      transoesophageal echocardiography.

PMID- 9659211
TI  - Images in cardiology. Primary angioplasty and stenting of left main coronary
      occlusion.

PMID- 9659212
TI  - Human stress cardiomyopathy mimicking acute myocardial syndrome.

PMID- 9659213
TI  - Effect of atrioventricular asynchrony on platelet activation.

PMID- 9659214
TI  - Lymphocyte trafficking: CD4 T cells with a 'memory' phenotype (CD45RC-) freely
      cross lymph node high endothelial venules in vivo.
AB  - Antigen encounter not only induces a change in surface expression of CD45RC
      isoforms in the rat from a high (CD45RC+) to a low molecular weight molecule
      (CD45RC-), but also stimulates changes in expression of adhesion molecules that
      regulate CD4 T-cell migration. T cells with an activated or 'memory' phenotype
      (CD45RC-) are thought to enter lymph nodes almost exclusively via afferent
      lymphatics whereas T cells in a resting state (CD45RC+) migrate across high
      endothelial venules (HEV). The present study monitored the rapid recirculation
      from blood to lymph of allotype-marked CD45RC T-cell subsets. Surprisingly, we
      found that CD45RC- CD4 T cells entered the thoracic duct slightly faster and
      reached peak numbers 3 hr earlier (18 hr) than did the CD45RC+ subset. To
      determine whether the entrance of CD45RC+ and RC- subsets was restricted to HEV
      and afferent lymphatics, respectively, recirculation of CD4 T cells was monitored
      in mesenteric lymphadenectomized (MLNx) rats (on healing the intestinal afferent
      lymphatics are joined directly to the thoracic duct), or in recipients that had
      had the mesenteric lymph node (MLN) acutely (2-3 hr) deafferentized (entry would
      be restricted to HEV). In these studies CD45RC- CD4 T cells entered the MLN
      across HEV on an equal basis with T cells expressing a CD45RC+ phenotype.
      Contrary to currently held dogma the results showed that, in vivo, CD4 T cells
      with a memory phenotype freely enter lymph nodes (LN) across HEV as well as via
      afferent lymphatics.

PMID- 9659216
TI  - Injection of T-cell receptor peptide reduces immunosenescence in aged C57BL/6
      mice.
AB  - Previous studies established that retrovirally infected young mice produced large
      amounts of autoantibodies to certain T-cell receptor (TCR) peptides whose
      administration diminished retrovirus-induced immune abnormalities. C57BL/6 young
      (4 weeks) and old (16 months) female mice were injected with these same synthetic
      human TCR V beta 8.1 or 5.2 peptides. Administration of these autoantigenic
      peptides to old mice prevent immunosenescence, such as age-related reduction in
      splenocyte proliferation and interleukin-2 (IL-2) secretion. TCR V beta peptide
      injection into young mice had no effect on T- or B-cell mitogenesis and IL-4
      production while modifying tumour necrosis factor-alpha (TNF-alpha), IL-6, and
      interferon-gamma (IFN-gamma) secreted by mitogen-stimulated spleen cells. TCR V
      beta injection also retarded the excessive production of IL-4, IL-6 and TNF-alpha
      induced by ageing. These data suggest that immune dysfunction and abnormal
      cytokine production, induced by the ageing process, were largely prevented by
      injection of selected TCR V beta CDR1 peptides.

PMID- 9659215
TI  - Protein kinase C mediates the signal for interferon-gamma mRNA expression in
      cytotoxic T cells after their adhesion to laminin.
AB  - A cytotoxic T-cell line, CTLL-2 cells, showed spreading after adhering to
      extracellular matrix proteins such as fibronectin (FN), laminin (LN) and
      hyarulonic acid (HA). The adhesion of CTLL-2 cells to LN was mediated by very
      late activation antigen-6 (VLA-6). Expression of interferon-gamma (IFN-gamma)
      mRNA was enhanced in CTLL-2 cells, also when they adhered to extracellular matrix
      proteins; and the enhanced IFN-gamma mRNA expression by adhering to LN was
      blocked by anti-alpha 6 antibody. Calphostin C, a protein kinase C (PKC)
      inhibitor, markedly inhibited the enhancement of IFN-gamma mRNA expression in a
      dose-dependent manner, which suggested that PKC acted as a second messenger in
      the IFN-gamma mRNA expression mediated by the interaction of VLA-6 with LN in
      CTLL-2 cells. Furthermore, confocal laser-microscopic analysis and Western blot
      analysis revealed that PKC-alpha was activated after CTLL-2 cells adhered to LN.
      PKC activity translocated from the cytosol fraction to the particulate fraction,
      after CTLL-2 cells adhered to LN. Altogether, we suggest that PKC plays an
      important role in the signal transduction for IFN-gamma mRNA expression after
      cytotoxic T cells adhere to LN.

PMID- 9659217
TI  - Cross-talk between V beta 8+ and gamma delta+ T lymphocytes in contact
      sensitivity.
AB  - We have previously reported that T lymphocytes proliferating in vitro to the
      hapten trinitrochlorobenzene (TNCB) exhibit a very restricted V beta gene usage
      and response to TNCB is limited to T-cell receptors (TCR) composed of V beta 8.2
      in combination with V alpha 3.2, V alpha 8 and V alpha 10. This paper
      investigates the role played by T lymphocytes expressing the V beta 8.2 gene
      segment in the contact sensitivity (CS) reaction to TNCB in the intact mouse and
      in its passive transfer into naive recipient mice. Mice injected with monoclonal
      antibodies to V beta 8 are unable to develop CS upon immunization with TNCB and 4
      day TNCB-immune lymph node cells from mice that had been depleted in vivo or in
      vitro of V beta 8+ T lymphocytes fail to transfer CS. However, when separated V
      beta 8+ and V beta 8- cells were used for passive transfer, it was found that V
      beta 8+ T lymphocytes failed to transfer CS when given alone to recipient mice
      and a V beta 8- population was absolutely required. Further analysis revealed
      that within the V beta 8- population, T lymphocytes expressing the gamma delta
      TCR were fundamental to allow transfer of the CS reaction. These gamma delta
      cells were found to be antigen non-specific, genetically unrestricted and to
      rearrange the V gamma 3 gene segment. This indicates that transfer of the CS
      reaction requires cross-talk between V beta 8+ and gamma delta+ T lymphocytes,
      thus confirming our previous results obtained using TNCB-specific T-cell lines.
      Time-course experiments showed that V beta 8+ lymphocytes taken 4-24 days after
      immunization with TNCB were able to proliferate and produce interleukin-2 (IL-2)
      in response to the specific antigen in vitro. Similar time-course experiments
      were then undertaken using the passive transfer of the CS reaction system. The
      results obtained confirm that TNCB-specific V beta 8+ T lymphocytes are present
      in the lymph nodes of immunized mice from day 4 to day 24, and reveal that gamma
      delta+ T lymphocytes are active for a very short period of time, i.e. days 4 and
      5 after immunization. In fact, TNCB-specific V beta 8+ cells are able to transfer
      CS when taken 4-24 days after immunization, providing the accompanying V beta 8-
      or gamma delta+ T lymphocyte are obtained 4 days after immunization. In contrast,
      injection of V beta 8+ T lymphocytes together with V beta 8- or gamma delta+ T
      lymphocytes that had been taken 2 or 6 days after immunization, failed to
      transfer significant CS into recipient mice. Taken together, our results confirm
      that cross-talk between V beta 8+ and gamma delta+ T lymphocytes is necessary for
      full development of the CS reaction and may explain why the CS reaction in the
      intact mouse lasts up to 21 days after immunization while the ability of immune
      lymph node cells to transfer CS is limited to days 4 and 5 after immunization.

PMID- 9659218
TI  - Investigation of the role of delayed-type-hypersensitivity responses to myelin in
      the pathogenesis of Theiler's virus-induced demyelinating disease.
AB  - The contribution of autoimmune responses to the pathogenesis of Theiler's virus
      induced demyelinating disease was investigated. Delayed-type hypersensitivity
      responses to myelin were examined in both symptomatic and asymptomatic mice at
      different times post-infection, in order to determine whether autoreactivity
      correlates with the development of demyelination. The results indicate that
      although autoimmune responses probably do not play a major role in the initiation
      of demyelination at early times post-infection, autoreactivity to myelin antigens
      dose eventually develop in symptomatic animals, perhaps through the mechanism of
      epitope spreading. Autoimmunity to myelin components is therefore an additional
      factor that may contribute to lesion progression in chronically diseased animals.

PMID- 9659219
TI  - Active suppression induced by cutaneous exposure to bacterial superantigen is
      prevented by interleukin-12 treatment in vivo.
AB  - Exposure to the bacterial superantigen staphylococcal enterotoxin B (SEB) leads
      to inhibition of several immune responses and the induction of regulatory cells.
      The aim of this study was to characterize these regulatory cells further and to
      investigate the effect of interleukin-12 (IL-12) on superantigen-induced
      suppression. For this purpose BALB/c mice were injected subcutaneously with low
      doses of SEB that did not deplete the SEB-reactive V beta T cells. Intravenous
      transfer of unseparated local-draining lymph node cells from these SEB-treated
      animals suppressed the proliferative response of mononuclear spleen cells of
      naive syngeneic recipients for at least 3 weeks. The regulatory cells did not
      produce the type 2 cytokines, interleukin-4 (IL-4) or interleukin-10 (IL-10), or
      increased amounts of transforming growth factor-beta (TGF-beta). Depletion of
      CD8+ or SEB-reactive V beta 7+ and V beta 8+ T cells, prior to transfer,
      abrogated the suppressive effect. Intraperitoneal injections of IL-12 into
      donors, prior to SEB treatment, prevented the induction of functional regulatory
      cells, and treatment of recipients with IL-12, prior to receipt of cells from SEB
      treated donors, prevented the suppressive effect of regulatory cells that were
      already induced. The data indicate that exposure to minute amounts of
      superantigens directly induces superantigen-reactive and CD8+ regulatory T cells
      and that superantigen-induced suppression can be prevented and reversed by IL-12
      treatment in vivo.

PMID- 9659220
TI  - Effect of T-helper cytokine environment on specificity of T-cell responses to
      mycobacterial 65,000 MW heat-shock protein.
AB  - The purpose of this work was to determine if the fine specificity of T cells
      differed between mice immunized with an antigen in a T helper 1 (Th1) cytokine
      dominated environment as compared with a T helper 2 (Th2) cytokine-dominated
      environment. It was found that splenic T cells from mice immunized with
      mycobacterial heat-shock protein (hsp 65) and interleukin-12 (IL-12) produced
      less interleukin-4 (IL-4) and more interferon-gamma (IFN-gamma) in response to
      stimulation with hsp 65 in vitro than did T cells from mice immunized with hsp 65
      alone. The T-cell proliferative response to hsp 65 did not differ between the two
      groups of mice, although the responses were higher than those of T cells from non
      immunized mice. Strikingly, T cells from mice given hsp 65 and IL-12 gave
      significantly higher responses to six peptides (corresponding to the sequence of
      hsp 65) to which T cells from mice immunized with hsp 65 alone did not respond.
      It is considered that different epitopes are presented to T cells (possibly owing
      to changes in antigen processing) if the environment is shifted, by IL-12, from
      Th2 towards Th1 cytokines.

PMID- 9659221
TI  - Regulation of interleukin-6 and interleukin-6R alpha (gp80) expression by murine
      immunoglobulin-secreting B-cell hybridomas.
AB  - We have examined the contribution of endogenous interleukin-6 (IL-6) to the
      differentiation of murine B-cell hybridomas. AT73 was established by somatic
      hybridization between BALB/c mice B cells and 2.52M, a hypoxanthine-aminopterine
      thymidine (HAT) medium-sensitive B-cell line mutant. It spontaneously secreted
      IgM, and addition of exogenous IL-6 augmented IgM secretion. Triggering of CD40
      led to an augmentation of IL-6 expression and IgM secretion. Blocking the binding
      of IL-6 to its cellular receptor through the use of inhibitory monoclonal
      antibodies inhibited CD40-induced IgM secretion, suggesting a possible autocrine
      role of IL-6 for the differentiation of a CD40-activated B-cell hybridoma. Co
      triggering with CD40 and B-cell receptor or activation through CD40 and IL-4 led
      to a synergistic augmentation of IL-6 expression as well as additive IgM
      secretion; this was followed by a marked decrease in the expression of B-cell
      surface markers on the cell membrane. Furthermore, under conditions where IL-6
      expression was augmented, gp80 expression was down-regulated, suggesting a
      negative feedback mechanism in this B-cell hybridoma. These findings provide a
      role by which T-cell-dependent activation through CD40 regulates an IL-6
      autocrine loop, controlling B-cell differentiation.

PMID- 9659222
TI  - Multiple signals regulate the intracellular trafficking of HLA-DM in B
      lymphoblastoid cells.
AB  - Peptide loading by major histocompatibility complex (MHC) class II molecules
      occurs in the endocytic pathway and is critically dependent upon the function of
      the class II-related molecule human leucocyte antigen-DM (HLA-DM). We have
      previously shown that a tyrosine-based lysosomal targeting signal present in the
      cytoplasmic tail of DMB has the capacity to target HLA-DM to peptide-loading
      compartments in HeLa cells. Here we investigate the importance of this signal in
      directing HLA-DM to processing compartments in professional antigen-presenting
      cells. We reconstituted a DMB-negative B-lymphoblastoid cell line with native or
      targeting-deficient DMB and show that in the absence of its tyrosine signal, DMB
      Y230A is as efficient as the wild-type molecule in inducing MHC class II SDS
      stable dimer formation; restoring expression of the conformation-dependent DR3
      epitope 16:23; the removal of CLIP; and accessing lysosomal peptide-loading
      compartments. By transient transfection in HeLa cells we show that Ii is able to
      compensate for loss of DMB-encoded targeting information. These data imply that
      in cells expressing physiological levels of class II, Ii and DM, there is
      sufficient association with Ii to direct the majority of DM into the endocytic
      pathway. Thus MHC class II and HLA-DM may follow similar intracellular
      trafficking pathways on route to antigen-processing compartments.

PMID- 9659223
TI  - Differential cytokine regulation of natural killer cell-mediated necrotic and
      apoptotic cytotoxicity.
AB  - Natural killer (NK) cells can kill target cells by either necrotic or apoptotic
      mechanisms. Using the 51Cr-release assay to measure necrotic death of target
      cells, neonatal NK cells had low NK activity (K562 targets) and high lymphokine
      activated killer (LAK) activity (Daudi targets) compared with adult cells, as has
      been previously reported. Using a 125I-deoxyuridine (125I-UdR) release assay,
      cord cells were shown to also have higher apoptotic LAK activity against YAC-1
      target cells. Interleukin-4 (IL-4) inhibited interleukin-2 (IL-2)-induced
      necrotic killing of target cells by adult effectors but had no such inhibitory
      effect on cord cells. In contrast, IL-4 inhibited both adult and cord LAK
      cytotoxicity of YAC-1 target cells by apoptotic mechanisms with higher
      suppression observed in cord cell preparations. Using a colorimetric substrate
      conversion assay, IL-2 induced higher, and IL-4 had a more significant
      suppressive effect on, cord cell granzyme B enzyme activity compared with adult
      cells, paralleling apoptosis cytotoxicity data. Co-culture of either adult or
      cord LAK cells with IL-4 had a similar inhibitory effect on granzyme B protein
      expression, as detected by Western blotting. In contrast, IL-4 did not inhibit
      perforin expression, thereby defining IL-4 as a cytokine that can differentially
      regulate the NK cell-mediated cytotoxicity processes of apoptosis and necrosis.
      The differential sensitivity of cord cells to cytokine regulation of cytotoxicity
      may also have implications for cord blood transplantations, as NK cells are known
      to function as an effector cell in both graft-versus-host disease and in the
      graft-versus-leukaemia phenomena.

PMID- 9659224
TI  - Interleukin-4 and interleukin-10 are chondroprotective and decrease mononuclear
      cell recruitment in human rheumatoid synovium in vivo.
AB  - We used the severe combined immunodeficient (SCID) mouse model to assess the
      effect of interleukin-4 (IL-4) or IL-10 injection on cartilage degradation and
      mononuclear cell (MNC) recruitment to human rheumatoid synovium in vivo. Human
      rheumatoid synovium and cartilage from five rheumatoid arthritis patients,
      obtained after joint replacement surgery, were engrafted subcutaneously to 6-8
      week-old SCID CB17 mice. Synovial tissues were injected with recombinant human IL
      4 (rhIL-4, 100 ng; rhIL-10, 100 ng), both cytokines, or tumour necrosis factor
      alpha (TNF-alpha) (1000 U), or phosphate-buffered saline twice a week for 4
      weeks. The graft was removed and immunochemical analysis was carried out to
      assess intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion
      molecule-1 (VCAM-1) and E-selectin expression. Moreover, cartilage degradation
      was assessed through the quantification of the erosion surface on a computerized
      image of the engrafted cartilage at high power view. MNC recruitment in the
      synovial tissue was determined by labelling blood MNC with indium-111 before
      their intraperitoneal injection. The activity obtained in the region of the graft
      were determined with a gamma camera 72 hr postinjection. The results are
      expressed as a percentage of initial injected activity. After 4 weeks we observed
      a decrease of cartilage area in controls (77 +/- 8%), inhibited after injection
      of IL-4, IL-10, or both cytokines (90 +/- 3%, 89.1 +/- 4%, 89.2 +/- 5%
      respectively), and 57 +/- 17% after TNF-alpha injection. The % MNC activity in
      the graft decreased to 77 +/- 81% (NS), 9 +/- 4% (P < 0.003) and 19 +/- 6% (P <
      0.007) compared with untreated synovial tissue after treatment with IL-4, IL-10,
      or both cytokines, respectively. Moreover, IL-10 but not IL-4 decreased the
      expression of ICAM-1 but not VCAM-1 or E-selectin by synovial cells. These
      results suggest that IL-10 and IL-4 could have chondroprotective properties, and
      that IL-10 but not IL-4 inhibits MNC traffic towards the synovial tissue
      efficiently.

PMID- 9659226
TI  - Rat mucosal mast cells: the cultured bone marrow-derived mast cell is
      biochemically and functionally analogous to its counterpart in vivo.
AB  - Mast cells (MC) are biochemically and functionally heterogeneous and the mixture
      of MC phenotypes varies according to anatomical location. Intestinal mucosal MC
      (IMMC) have been used to study the mucosal MC subset in the rat, but they are
      difficult to isolate in sufficient numbers and with consistent purity and
      viability. Bone marrow-derived MC (BMMC), with an apparent mucosal MC phenotype,
      can be cultured in large numbers and with high purity from normal rat bone marrow
      using supernatants from mesenteric lymph node cells of rats infected with the
      nematode, Nippostrongylus brasiliensis. We have compared serine proteinase
      content, tumour necrosis factor-alpha (TNF-alpha) storage and secretion, and TNF
      alpha-dependent cytotoxicity of IMMC and BMMC to assess the appropriateness of
      BMMC as in vitro models of mucosal MC. Two-dimensional gel electrophoretic
      analysis revealed that the overall protein constituents of BMMC and IMMC were
      highly homologous. Immunoblotting confirmed that both MC types expressed the MMC
      associated enzyme, rat mast cell proteinase-2 (RMCP-2), but not RMCP-1, mast cell
      proteinase-5 (MCP-5) or carboxypeptidase A (CPA), which characterize the
      connective tissue MC in the rat and which were detected in a representative of
      this subset, namely, the periotoneal MC (PMC). BMMC demonstrated levels of TNF
      alpha-dependent cytotoxicity that were equivalent to those of IMMC. Like IMMC,
      BMMC contained little stored TNF-alpha, in comparison with PMC, but both MC types
      generated substantial amounts of TNF-alpha 6 hr following IgE-mediated
      activation. Pretreatment of PMC with recombinant rat interferon-gamma (IFN-gamma)
      for 20 hr inhibited anti-immunoglobulin E (anti-IgE)-mediated release of the
      granule-associated enzyme, beta-hexosaminidase, whereas identically treated BMMC
      were unresponsive to this cytokine. Similar results have previously been reported
      for IMMC. Rat BMMC, unlike their more immature and less phenotypically committed
      counterparts in the mouse, appear therefore to be more appropriate models for
      studies on the mucosal MC.

PMID- 9659225
TI  - Peritoneal macrophages play an important role in eliminating human cells from
      severe combined immunodeficient mice transplanted with human peripheral blood
      lymphocytes.
AB  - To elucidate the mechanism of human cell elimination from severe combined
      immunodeficient (SCID) mice transplanted with human peripheral blood lymphocytes
      (hu-PBL-SCID mice), we explored the immunocytes in the peritoneal cavity in SCID
      mice where human PBL were transferred. When the phenotype of peritoneal exudate
      cells (PEC) was compared by flow cytometry among three congenic strains of SCID
      mice that differ in their acceptability for human PBL, the PEC in NOD-scid mice,
      which exhibit the highest acceptability, contained the smallest number of
      F4/80lo/-Mac-1(+)-activated macrophages. Moreover, the proportions of natural
      killer cells in PEC of the three strains of SCID mice were not always correlated
      with the acceptability. These findings suggest the possibility that peritoneal
      macrophages eliminate human cells in hu-PBL-SCID mice. To verify this hypothesis,
      we evaluated the engraftment of human PBL into SCID mice that were treated with
      liposome-encapsulated dichloromethylene diphosphonate, which selectively depletes
      macrophages by inducing apoptosis, or 8-aminoguanidine hemisulphate salt, an
      inhibitor of inducible nitric oxide synthase of macrophages. As a result, both of
      these regimens improved engraftment of human PBL, indicating that peritoneal
      macrophages take part in human cell elimination in the peritoneal cavity of hu
      PBL-SCID mice and that it is mediated, at least in part, by direct macrophage
      cytotoxicity utilizing nitric oxide.

PMID- 9659227
TI  - Lactic dehydrogenase virus infection enhances parasite egg production and
      inhibits eosinophil and mast cell responses in mice infected with the nematode
      Nippostrongylus brasiliensis.
AB  - The effects of lactic dehydrogenase virus (LDV) infection on the protective
      immune responses to the nematode Nippostrongylus brasiliensis were studied. Mice
      with chronic LDV infection showed significantly higher levels of parasite egg
      production than non-LDV-infected (control) mice after N. brasiliensis infection.
      Concurrent LDV infection also suppressed peripheral blood eosinophilia and the
      lung mastocytosis induced by this nematode. LDV infection showed higher
      expression levels of the interferon-gamma (IFN-gamma) mRNA in lymph nodes
      compared with control mice before N. brasiliensis infection. In addition, the
      IgG2a production in LDV-infected mice was higher than that in control mice before
      and after N. brasiliensis infection. These results suggest that LDV infection
      modulates protective immune responses against N. brasiliensis infection by the
      activation of T-helper type 1 cells.

PMID- 9659228
TI  - Post-translational modification and intracellular localization of a splice
      product of CD46 cloned from human testis: role of the intracellular domains in O
      glycosylation.
AB  - We obtained a unique CD46 cDNA, STc/CY4, from the human testis, the predicted
      amino acid sequence of which suggested the presence of a novel isoform of CD46.
      This message was present predominantly in the testis, and the predicted isoform
      possessed a short (11 amino acids) transmembrane section (TM) and an unidentified
      cytoplasmic tail (CY). When expressed in Chinese hamster ovary (CHO) cells, this
      CD46 isoform underwent no O-glycosylation and was mostly retained in the
      endoplasmic reticulum. This unusual behaviour of the new isoform was due in part
      to the short TM and the unusual sequences of the CY. The molecular mass of this
      isoform was 42,000, approximately 20,000 smaller than conventional CD46. These
      properties of the STc/CY4 isoform were similar to those of sperm CD46. The only
      difference between sperm CD46 and the STc/CY4 isoform expressed on CHO cells was
      that only the latter possessed N-linked sugars of high mannose types. Since the
      STc/CY4 isoform may behave like sperm CD46 in cellular localization and post
      translational modification, studies of sperm-egg interassociation were performed
      using hamster eggs and CHO cell clones expressing various isoforms including the
      STc/CY4. Rosette formation was seen most effectively between hamster eggs and
      STc/CY4-expressing CHO cells. These results infer that O-glycosylation perturbs
      CD46-mediated sperm-binding to eggs and thus sperm CD46 lacking O-linked sugars
      can serve as an adhesion molecule. The possible role of CD46 in fertilization and
      the structural differences between sperm and conventional CD46 are discussed.

PMID- 9659229
TI  - Preservation of mucosal and systemic adjuvant properties of ISCOMS in the absence
      of functional interleukin-4 or interferon-gamma.
AB  - Adjuvants are a critical component of non-viable vaccine vectors, particularly
      for those to be used via mucosal routes. Although most adjuvants act by inducing
      local inflammatory responses, the molecular basis of many of these effects is
      unclear. Here we have investigated whether interleukin-4 (IL-4) and interferon
      gamma (IFN-gamma) are required for the induction of local and systemic immune
      responses by oral and parenteral administration of ovalbumin (OVA) in immune
      stimulating complexes (ISCOMS), a potent mucosal adjuvant vector. Our results
      show that after oral or systemic immunization with OVA ISCOMS, IL-4 knockout
      (IL4KO) and IFN-gamma receptor knockout (IFN-gamma RKO) mice develop an entirely
      normal range of immune responses including delayed-type hypersensitivity (DTH),
      serum immunoglobulin G (IgG) antibodies, T-cell proliferation and cytokine
      production, class I major histocompatibility complex (MHC)-restricted cytotoxic T
      lymphocyte (CTL) activity and intestinal IgA antibodies. These responses were of
      a similar magnitude to those found in the wild-type mice, indicating that the
      immunogenicity of ISCOMS is not influenced by the presence of IL-4 or IFN-gamma
      and emphasizing the potential of ISCOMS as widely applicable mucosal adjuvants.

PMID- 9659230
TI  - Intranasal immunization of mice with herpes simplex virus type 2 recombinant gD2:
      the effect of adjuvants on mucosal and serum antibody responses.
AB  - Mucosal immunization offers the potential for inducing IgA antibody responses in
      the vagina, the site of infection for many viruses, including herpes simplex type
      2 (HSV-2). To investigate this possibility, mice were immunized intranasally with
      10 micrograms glycoprotein D2 (gD2) from HSV combined with a series of adjuvants
      of proven efficacy; the oil in water emulsion MF59, poly(D,L-lactide-co
      glycolide) microparticles (PLG) (encapsulated or co-administered), immune
      stimulating complexes (iscoms) (incorporated or co-administered with iscomatrix)
      and the genetically detoxified enterotoxin from Escherichia coli, LT-K63.
      Encapsulation of gD2 into PLG microparticles, incorporation of gD2 into iscoms
      and co-administration of gD2 with LT-K63 induced mucosal IgA antibody responses
      (nasal wash, saliva and vaginal wash) which were greater than those induced by
      intramuscular administration of gD2 with MF59. Intranasal immunization with these
      formulations also induced substantial levels of serum IgG and neutralizing
      antibodies. These studies demonstrated that intranasal immunization with potent
      adjuvants is an effective means to induce mucosal antibody responses, even in the
      lower genital tract.

PMID- 9659231
TI  - Antibodies with idiotypic and anti-idiotypic reactivity (epibodies) in
      conventional immune responses to dinitrophenylated carriers.
AB  - A number of monoclonal antibodies were derived from the spleen cells of
      dinitropheryl (DNP)-immunized mice. Both T-dependent and T-independent carriers
      were used, and the intensity and length of immunization were varied. It was found
      that some of the antibodies had only idiotypic (Ab1) reactivity, while others had
      both idiotypic (Ab1) and anti-idiotypic (Ab2) reactivity. Among the latter
      antibodies some molecules reacted specifically with DNP and with the combining
      site of anti-DNP antibodies (epibodies), while others bound DNP and anti-DNP Abs
      as well as a variety of unrelated antigens (polyreactive antibodies). The
      proportion of the three types of antibodies (antigen-specific, epibodies and
      polyreactive antibodies) varied with the nature of the carrier, the intensity of
      the immunization, and the length of the immunization process. Further
      characterization of the epibodies, which were predominant in the secondary
      response to DNP-keyhole limpet haemocyanin (KLH), showed that both Ab1 and Ab2
      reactivities were inhibited by both soluble ligands (DNP and anti-DNP),
      indicating that the specific combining site of the monoclonal antibodies (mAbs)
      (and/or of the rabbit anti-DNP antibody in the case of Ab2) was involved in both
      activities. Both Ab1 and Ab2 reactivities were removed by absorption of the mAbs
      with either immobilized DNP or immobilized rabbit anti-DNP. The mAbs were capable
      of binding themselves as well as to other mAbs with the same characteristics. The
      affinity constants of several mAbs for both the DNP and anti-DNP ligands were
      determined.

PMID- 9659232
TI  - Characterization of the gene for the membrane and secretory form of the IgM heavy
      chain constant region gene (C mu) of the cow (Bos taurus).
AB  - Our present understanding of the evolution of immunoglobulins is derived from a
      few vertebrate species. In order to obtain additional information on the
      development of the humoral immune system, we cloned and determined the nucleotide
      sequence of the bovine cDNA and genomic IgM heavy-chain constant region gene (C
      mu). The gene contains four constant region domain-encoding exons (CH1 to CH4)
      and two exons encoding the transmembrane domain (TM1, TM2), expressed in the
      membrane-bound receptor form of the IgM. The sequence of a cDNA clone encoding
      the 3' portion of the membrane form of the mu-chain revealed that the TM1 exon is
      spliced to the CH4 exon, as occurs in other mammals. Comparison of deduced amino
      acid sequence data from different vertebrates revealed a high similarity to sheep
      C mu (88%) and a lower degree of similarity to pig (62%), rat (62%), rabbit (58%)
      human (56%), hamster (55%), mouse (54%), chicken (28%) and horned shark (22%) C
      mu.

PMID- 9659233
TI  - Specific inhibition of immunoglobulin E-mediated allergic reaction using
      antisense Fc epsilon RI alpha oligodeoxynucleotides.
AB  - We have investigated the ability of an antisense immunoglobulin E (IgE) receptor
      alpha-subunit oligodeoxynucleotide (Fc epsilon RI alpha ODN) specifically to
      inhibit IgE-mediated allergic reactions in the mouse. Synthetic antisense Fc
      epsilon RI alpha ODN dose-dependently inhibited passive cutaneous anaphylaxis and
      histamine release from the mouse peritoneal mast cells (MPMC) activated by anti
      dinitrophenyl (DNP) IgE. Northern blot analysis showed that the mast cells
      treated with antisense Fc epsilon RI alpha ODN exhibited no detectable levels of
      L-histidine decarboxylase mRNA after anti-DNP IgE stimulation, whereas the cells
      treated with sense Fc epsilon RI alpha ODN possessed significant amounts of this
      mRNA. Examination of the elevation of cAMP levels in MPMC following the
      activation with anti-DNP IgE demonstrated a significant rise in activated cells,
      but not in the antisense Fc epsilon RI alpha ODN-treated cells. Moreover,
      antisense Fc epsilon RI alpha ODN had a significant inhibitory effect on anti-DNP
      IgE-induced tumour necrosis factor-alpha production. Our results demonstrated
      that antisense Fc epsilon RI alpha ODN inhibited the IgE-mediated allergic
      reaction in vivo and in vitro.

PMID- 9659234
TI  - Activation of complement by human IgG1 and human IgG3 antibodies against the
      human leucocyte antigen CD52.
AB  - Activation of the complement cascade by immunoglobulin G (IgG) plays a major role
      in the host defense against pathogens. Using recombinant human antibodies
      specific for the leucocyte antigen CD52, different allotypes of human IgG1
      subclass were compared for their ability to activate human complement. In
      addition the roles of the different length hinge regions of IgG1 and IgG3 were
      investigated. It was found that the naturally occurring allotypes G1m(a,z) and
      G1m(f), and one artificially created isoallotype, G1m(null), did not
      significantly differ in their overall ability to cause cell lysis. However, some
      differences in binding of individual components of the classical activation
      pathway were detected. More of the complement component C1s seemed to be
      associated with the allotype G1m(f), although this did not result in an overall
      improvement in lytic potency. In this system the wild-type IgG3 was found to be
      less effective in complement lysis than IgG1. By shortening the hinge region of
      IgG3 to resemble that of an IgG1 antibody, increased complement binding was
      observed compared with that of wild-type IgG3 and the IgG1 allotypes. The overall
      lytic potency of the antibody was also improved compared with wild type IgG3 and
      it was also slightly more effective than the IgG1 allotypes.

PMID- 9659235
TI  - Imaging bioluminescent indicators shows Ca2+ and ATP permeability thresholds in
      live cells attacked by complement.
AB  - A series of permeability thresholds to Ca2+ metabolites and macromolecules,
      occurring at different times when cells are attacked by complement, has been
      established by imaging HeLa cells transiently expressing a recombinant cytosolic
      fusion protein of firefly luciferase and aequorin (luciferase-aequorin) to
      measure changes in ATP and cytosolic free Ca2+. Nuclear fluorescence of propidium
      was used as a measure of permeability to small molecules, and luciferase activity
      imaged to assess lysis. The rise in cytosolic free Ca2+ observed after C9 attack
      preceded by at least 60 s both the increase in propidium fluorescence, measured
      in single cells, and the decrease in ATP monitored by luciferase light emission.
      These effects were dependent on the concentration of C9. At concentrations of C9
      up to 4 micrograms/ml no loss of luciferase-aequorin protein was detected at the
      end of the experiment. Thus the membrane integrity of the cells remained intact,
      even though the cells were permeable to propidium. These results confirmed our
      earlier observations that propidium permeability in cells attacked by complement
      was not a reliable measure of cell death. They also show that it is vital to take
      account of cellular heterogeneity if the mechanisms by which cells respond to
      membrane pore former attack are to be correctly interpreted.

PMID- 9659236
TI  - Prion diseases: what will be next?

PMID- 9659237
TI  - Application of molecular typing to the epidemiology of Streptococcus pneumoniae.
AB  - The spread of antibiotic resistance and the development of new vaccines have
      focused attention on the epidemiology of Streptococcus pneumoniae over recent
      years. While serotyping and the determination of antibiotic resistance remain
      primary methods for characterising pneumococci, molecular typing can add greater
      discrimination and complementary information. Methods based on restriction
      fragment length polymorphism within total DNA or non-specific polymerase chain
      reaction provide information representative of the whole genome and can be used
      to recognise closely related isolates from different sources, whether in the
      investigation of possible cross infection at the local level or in the
      investigation of national or international spread of antibiotic resistant
      strains. Fingerprinting of penicillin binding protein genes adds further
      information in the analysis of penicillin resistant isolates. The use of a
      combination of typing methods to analyse both the genome as a whole and specific
      loci has led to the realisation that pneumococci undergo horizontal gene transfer
      much more often than most other bacterial species. In particular the spread of
      penicillin resistance has been characterised by a combination of the spread of
      epidemic strains, transfer of chromosomal resistance genes from such strains into
      other genetic backgrounds, and transfer of capsule genes resulting in the switch
      of serotypes within strains. In the future molecular typing will have an
      important role in discovering whether widespread vaccination leads to genetic
      modification of the pneumococcal population causing invasive disease.

PMID- 9659238
TI  - The importance of "like to like" ISI calibrations with freeze dried plasmas.
      European Concerted Action on Anticoagulation.
AB  - AIM: To assess reliability of like to like and cross species calibrations using
      two types of certified freeze dried plasma calibrants--artificially depleted of
      vitamin K clotting factors, and from coumarin treated patients. METHODS: Six ECAA
      national control laboratories provided certified values for the freeze dried
      plasmas in terms of the human plain international reference preparation (IRP)
      (BCT/441) with the manual prothrombin time technique. Eight other ECAA national
      laboratories determined international sensitivity index (ISI) values in full
      fresh plasma same species and cross species WHO calibrations against a low ISI
      human IRP (BCT/441) of the ECAA low ISI human thromboplastin and high ISI ECAA
      rabbit thromboplastin. Parallel calibrations were performed using the certified
      values. RESULTS: Calibrations on fresh plasmas of the human ECAA reference
      thromboplastin (stated ISI = 0.95) gave ISI of 0.957 against the human IRP and
      1.66 against the rabbit IRP. The ECAA rabbit (stated ISI = 1.67) gave an
      identical value on the fresh plasma calibration v the human IRP. With freeze
      dried depleted plasmas certified in terms of the human IRP, the ISI of the ECAA
      human was 1.01, but the ECAA rabbit (stated ISI = 1.67) gave a low ISI of 1.47.
      The freeze dried coumarin plasmas gave an ISI of 0.943 for the ECAA human but
      only 1.493 for the ECAA rabbit. CONCLUSIONS: Fresh plasmas give reliable ISI when
      calibrating thromboplastins in same species and cross species calibrations.
      Freeze dried plasmas certified in terms of a single IRP, whether artificially
      depleted or of coumarin plasma origin, cannot be used for calibration of
      dissimilar thromboplastins.

PMID- 9659239
TI  - Ticlopidine induced colitis: a histopathological study including apoptosis.
AB  - AIMS: To describe ticlopidine related microscopic colitis and to assess the
      occurrence of apoptosis in the colon epithelium. METHODS: A series of colorectal
      biopsy samples from nine patients with ticlopidine related chronic diarrhoea were
      analysed. Biopsies were also taken from five of these patients between two and
      four months after ticlopidine withdrawal. The number of apoptotic cells in the
      crypts/mm2 (apoptotic index) was calculated using in situ labelling by terminal
      deoxyribonucleotidyl transferase (TdT) mediated dUTP-biotin nick end labelling
      (TUNEL). All specimens were matched to normal colorectal specimens from a control
      group of comparable age and sex distribution. RESULTS: Histological examination
      of the colon biopsy specimens taken from all nine patients with ticlopidine
      related chronic diarrhoea showed characteristic features of microscopic colitis.
      The histology returned to normal when ticlopidine was withdrawn. Apoptotic cells
      were rarely found in controls, and the mean apoptotic index was 0.53. The
      apoptotic index was significantly higher (16.53) in ticlopidine related colitis,
      but decreased dramatically to control value when ticlopidine was withdrawn.
      CONCLUSION: Microscopic colitis can be induced by ticlopidine and is accompanied
      by an increase in epithelial apoptosis. Hence, increased apoptosis might be
      related to drug injury or might be part of microscopic colitis.

PMID- 9659240
TI  - Telomerase expression shows differences across multiple regions of
      oligodendroglioma versus high grade astrocytomas but shows correlation with Mib-1
      labelling.
AB  - AIMS/BACKGROUND: Telomerase is an enzyme that is expressed in most human
      neoplasms and is associated with tumour immortality. Determination of the point
      in neoplastic transformation at which telomerase is expressed may aid the
      understanding of tumour pathogenesis and progression. Despite numerous reports on
      telomerase, few studies have investigated its expression in high grade glial
      tumours. These studies, performed on archival banked, single brain tumour
      specimens, have shown conflicting results for oligodendrogliomas and unexpectedly
      negative results for telomerase expression in high grade astrocytomas, with one
      third to one half of glioblastoma multiformes being negative. METHODS: 34 rapidly
      banked glioma specimens taken from patients undergoing gross total surgical
      resection of their tumours were studied. Telomerase expression was assessed
      across 3-8 sampled regions from each tumour by the telomeric repeat amplification
      protocol (TRAP) assay. Matched mirror image tissue samples were taken for
      histological analysis of tissue adequacy, statistical correlation of telomerase
      with tumour histological features, Mib-1 (a marker for cell cycling) labelling,
      and p53 immunohistochemistry. RESULTS: All five well differentiated
      oligodendrogliomas were homogeneously telomerase negative and two of three
      untreated anaplastic oligodendrogliomas were homogeneously positive. In contrast,
      10 of 14 high grade astrocytomas showed heterogeneity for telomerase expression
      across the multiple regions sampled. All glioblastoma multiformes and two of
      three anaplastic astrocytomas showed at least one region positive for telomerase.
      When test samples were individually assessed in both oligodendrogliomas and high
      grade astrocytomas, telomerase expression was associated with Mib-1 labelling (p
      < 0.001). For the entire group, telomerase expression was associated with grade
      of tumour, age of patient, and vascular endothelial proliferation (all p <
      0.001). CONCLUSIONS: This regional study clarifies that all glioblastoma
      multiformes are at least focally positive and that telomerase expression
      correlates with tumour grade in oligodendrogliomas. Homogeneity versus
      heterogeneity for telomerase expression across multiple regions of
      oligodendrogliomas versus high grade astrocytomas may provide important
      preclinical data on the use of antitelomerase agents in these adult glial
      tumours.

PMID- 9659241
TI  - Genetic polymorphism of N-acetyltransferase-2, glutathione S-transferase-M1, and
      cytochromes P450IIE1 and P450IID6 in the susceptibility to head and neck cancer.
AB  - AIMS: To analyse the allele frequencies of DNA polymorphisms at the genes for
      cytochromes P450IIE1 and P450IID6, N-acetyltransferase-2, and glutathione S
      transferase-M1 in patients with head and neck squamous cell carcinoma, in an
      attempt to define genetic factors involved in the susceptibility to this cancer,
      which is strongly associated with tobacco consumption. METHODS: Determination of
      restriction fragment length polymorphism (RFLP) at cytochromes P450IIE1/P450IID6
      and NAT2 genes, and the presence of homozygous deletion of the GSTM1 gene, in 200
      controls and 75 head and neck cancer patients. Allelic frequencies between the
      two groups were compared using a chi 2 test, and odds ratio with 95% confidence
      intervals were calculated. RESULTS: There was no evidence of an association
      between alleles of CYP2D6 and CYP2E1 and head and neck cancer in our population.
      Similarly, frequencies of individuals lacking the GSTM1 gene did not differ
      between controls and patients. However, individuals with the NAT2-SA phenotype
      were at higher risk of developing head and neck cancer. The frequencies of the
      most common SA genotype (homozygous for the NAT2*5 allele) were higher in
      patients than in controls (27% v 15%, respectively). Slow acetylators homozygous
      for the NAT2*6 allele, the second most common SA allele, were also more common in
      patients than in controls (11% v 5%, respectively). CONCLUSIONS: Slow NAT2
      activity is a risk factor possibly leading to the development of head and neck
      cancer in response to tobacco carcinogens.

PMID- 9659242
TI  - Evaluation of Helicobacter pylori vacA genotype in Japanese patients with gastric
      cancer.
AB  - AIM: To examine the vacA genotypes of Helicobacter pylori strains in Japan and to
      define whether any specific genotype was associated with gastric cancer. METHODS:
      The allelic variation of vacA gene was studied using a recently introduced
      polymerase chain reaction based vacA genotyping system. RESULTS: 80 H pylori
      strains were isolated from gastric biopsies of 40 patients with gastric cancer
      and 40 control subjects in a Japanese population. All strains were s1/m1 subtype
      and 79 of 80 strains were classified as s1a subtype. CONCLUSIONS: The recently
      proposed vacA genotyping system is applicable to Japanese H pylori strains and
      most strains have the s1a genotype, associated with increased virulence. While
      the high frequency of s1a/m1 vacA genotype might play a role in the increased
      incidence of atrophic gastritis and gastric cancer in Japanese subjects, it
      precludes its use as a predictor of clinical outcome of H pylori infection in
      Japan.

PMID- 9659243
TI  - Experience of changing between signal and Bactec 9240 blood culture systems in a
      children's hospital.
AB  - AIM: To compare experience of positive blood cultures in successive years before
      and after changing from Signal (Unipath) to Bactec 9240 (Becton Dickinson) blood
      culture systems. METHODS: Analysis of data collected prospectively on 7967 Signal
      and 7062 Bactec blood culture sets. RESULTS: Significant growths occurred in 5.7%
      of Signal and 8.9% of Bactec cultures; 33.0% more significant isolates and 24.0%
      more episodes of bacteraemia were detected in the second year, following
      introduction of the Bactec system. Inpatient hospital activity increased by 8.2%
      between the first and second years, although the numbers of blood cultures
      received actually fell by 11.4%. There were striking increases in numbers of
      isolates of coagulase negative staphylococci (47.7%) and Enterobacteriaceae
      (56.8%) from Bactec cultures. Two anaerobic bacteraemias were detected in Signal
      blood cultures, whereas none was detected by the Bactec system, despite 12.1% of
      sets including an anaerobic bottle. Of significant positive cultures, 90.2% were
      detected within one day with the Bactec 9240, compared with only 50.0% of Signal
      cultures; 20.7% of significant positive Signal blood cultures were detected only
      on terminal subculture. Microorganisms that were not significant were isolated
      from 5.1% Signal and 3.8% Bactec cultures. CONCLUSIONS: Compared with the Signal
      system, the Bactec 9240 offers markedly more rapid and sensitive detection of
      bacteraemia, together with a lower rate of non-significant isolates. However,
      using a single PEDS PLUS/F bottle the few episodes of anaerobic bacteraemia that
      occur in children are likely to be missed.

PMID- 9659244
TI  - The inhibitory effect of phosphate on the ligase chain reaction used for
      detecting Chlamydia trachomatis.
AB  - AIMS: To examine the detection limit of the ligase chain reaction kit for
      Chlamydia trachomatis, to study the inhibitory effect of phosphate on the ligase
      chain reaction, and to clarify the mechanism of inhibition. METHODS: Three
      reference serovars of C trachomatis--D/UW-3/Cx, F/UW-6/Cx, and L2/434/Bu--were
      used to test the sensitivity of the chlamydia ligase chain reaction. Comparison
      was made of the inhibition by phosphate before and after DNA amplification.
      Phosphate in up to 2.4 mM concentration was added to specimens of C trachomatis
      serovar D (1 to 50 inclusion forming units (IFU)/reaction) before DNA
      amplification to examine the concentration dependency of phosphate inhibition of
      the ligase chain reaction. RESULTS: The detection limits were 0.6 IFU/reaction
      for serovar D/UW-3/Cx and F/UW-6/Cx, and 0.4 IFU/reaction for L2/434/Bu.
      Phosphate inhibited the ligase chain reaction only when it was added before the
      amplification stage. The specimens containing chlamydia at 1 to 50 IFU/reaction
      were negative when the concentration of phosphate added at the prethermocycle
      stage was more than 1.2 mM. CONCLUSIONS: Ligase chain reaction analysis is a
      reliable method of diagnosing C trachomatis infection because of its high
      sensitivity. It would be clearly superior to the currently used methods if the
      problem of inhibitors could be eliminated. The mechanism of inhibition of the
      ligase chain reaction by phosphate was thought to be blockade of the
      amplification of the target DNA. The efficacy of the ligase chain reaction could
      be inhibited by phosphate in the urine, so duplicate dilution analysis of some
      negative specimens should be useful.

PMID- 9659245
TI  - Comparison of throat swabs with sputum specimens for the detection of Chlamydia
      pneumoniae antigen by direct immunofluorescence.
AB  - AIM: To compare throat swabs with sputum specimens for Chlamydia pneumoniae
      antigen detection. METHODS: During a one year period, sputum and throat swabs
      from 50 patients over 15 years of age with acute or persisting lower respiratory
      tract infection were examined for C pneumoniae antigen by direct
      immunofluorescence. RESULTS: C pneumoniae antigen was detected in 18/50 patients
      (36.0%) from sputum, throat swab, or both. Paired sputum and throat swabs were
      received from 35/50 patients (70.0%). C pneumoniae antigen was detected in either
      or both specimens from 14/35 patients (40.0%). Of the 14 positive patients, both
      specimens were positive in nine (64.3%), throat swab only in four (28.6%), and
      sputum only in one (7.1%). Of the remaining 15 patients from whom only a single
      specimen was sent, a further three of eight throat swabs and one of seven sputum
      specimens were positive. There was no statistically significant difference
      between the results obtained from the two types of specimen. CONCLUSIONS: Throat
      swabs may be as good as sputum for the detection of C pneumoniae antigen.

PMID- 9659247
TI  - The Vitek analyser for routine bacterial identification and susceptibility
      testing: protocols, problems, and pitfalls.
AB  - Automated and semiautomated technology in microbiology has seen great advances in
      recent years. The choice of automated equipment for the identification and
      susceptibility testing of bacteria in a routine diagnostic laboratory depends on
      speed, accuracy, ease of use, and cost factors. The Vitek analyser (bioMerieux,
      UK) was installed in a busy diagnostic teaching hospital laboratory in London.
      This report describes one year's experience. Changes to work practice as a result
      of incorporating the equipment into the laboratory, and the advantages and
      disadvantages of automation in key areas are described in detail, together with
      possible solutions to problems. The Vitek analyser was found to be valuable for
      the speed and accuracy with which results were available for the common bacterial
      pathogens. Results of susceptibility testing were standardised according to NCCLS
      guidelines and used breakpoint MICs to ascertain susceptibility and resistance;
      they were an improvement on disc testing. This equipment is not a reference
      facility for difficult to identify organisms and many manual techniques,
      including some disc susceptibility testing, will have to be retained by the
      laboratory.

PMID- 9659246
TI  - Do IgA, IgE, and IgG avidity tests have any value in the diagnosis of toxoplasma
      infection in pregnancy?
AB  - AIM: To determine the value of tests for specific IgA, IgE, and IgG avidity in
      diagnosing Toxoplasma gondii infection during pregnancy. METHODS: In a
      retrospective study, current serological tests (dye test and three IgM assays
      with different sensitivities) were compared with immunosorbent agglutination
      assays (ISAGA) for specific IgA and IgE and an IgG avidity enzyme linked
      immunosorbent assay (ELISA). Patient group 1 comprised six women with definite or
      probable infection during pregnancy determined by congenital toxoplasmosis or
      laboratory results. Group 2 comprised seven women infected during or before 11
      pregnancies (two consecutive pregnancies in two patients and three in a third).
      RESULTS: One patient in group 1 seroconverted during pregnancy. IgA ISAGA and
      avidity confirmed acute infection when confirmatory IgM ELISA remained negative.
      In five of six patients from group 1, IgA and IgE ISAGA and avidity confirmed
      acute infection. In group 2, the dye test titre was raised in seven of 11
      pregnancies (six of seven patients). Specific IgM and IgA were positive during
      all 11 pregnancies. IgE ISAGA was positive in only four of 11 pregnancies (three
      of seven patients), but negative results in the remainder may exclude acute
      infection. High avidity antibodies indicative of past infection were found in
      four of 11 pregnancies (two of seven patients). CONCLUSIONS: Each test improved
      diagnosis or timing of infection but no single test was ideal. The IgA ISAGA was
      sensitive and detected seroconversion. Positive IgE ISAGA and low avidity both
      confirmed infection, whereas negative IgE may exclude acute infection. High
      avidity diagnosed past infection but persistence of low avidity reduced its value
      to differentiate acute and past infection. Further studies with larger patient
      groups are needed to determine the optimum diagnostic strategy. These techniques
      are valuable in complementing existing tests.

PMID- 9659248
TI  - Apolipoprotein E alleles in women with severe pre-eclampsia.
AB  - This study investigated the frequency of apolipoprotein E (apoE) alleles among
      women with severe pre-eclampsia. The presence of the three most common apoE
      alleles (epsilon 2, epsilon 3, epsilon 4) was determined by polymerase chain
      reaction-restriction fragment length polymorphism in three groups of white women:
      non-pregnant healthy (n = 101), pregnant healthy (n = 52), and pregnant with a
      diagnosis of severe pre-eclampsia (n = 54). The frequency of apo epsilon 2 was
      highest among women with severe pre-eclampsia (16.6%) followed by non-pregnant
      women (12.9%), and those experiencing a healthy pregnancy (10.6%). The higher
      frequency of the apo epsilon 2 allele detected among women with severe pre
      eclampsia suggests that apoE may play a role in the development of pre-eclampsia.

PMID- 9659250
TI  - Pathologists dislike sound? Evaluation of a computerised training microscope.
AB  - AIM: To evaluate the use of multimedia enhancements, using a computerised
      microscope, in the training of microscope skills. METHODS: The HOME microscope
      provides facilities to highlight features of interest in conjunction with either
      text display or aural presentation. A pilot study was carried out with 10
      individuals, eight of whom were at different stages of pathology training. A
      tutorial was implemented employing sound or text, and each individual tested each
      version. Both the subjective impressions of users and objective measurement of
      their patterns of use were recorded. RESULTS: Although both versions improved
      learning, users took longer to work through the aural than the text version; 90%
      of users preferred the text only version, including all eight individuals
      involved in pathology training. CONCLUSIONS: Pathologists appear to prefer visual
      rather than aural input when using teaching systems such as the HOME microscope
      and sound does not give added value to the training experience.

PMID- 9659249
TI  - A method for the confirmation and identification of drugs of misuse in urine
      using solid phase extraction and gas-liquid chromatography with mass
      spectrometry.
AB  - A method is described for the confirmation/identification of a range of commonly
      misused drugs in urine samples. The method has been used for two years without
      problems for a range of purposes including hospital/clinic drugs of misuse
      screening and for toxicology in coroner's cases. Urine samples which have given a
      positive result on immunochemical screening for a particular drug group or groups
      (for example, opiates) can be processed with identification of the drugs present
      using a single procedure. Bond ElutCertify columns are used for the extraction of
      drugs from the samples followed by propionylation and gas chromatography with
      mass selective detection.

PMID- 9659251
TI  - Spontaneous regression of renal cell carcinoma: a pitfall in diagnosis of renal
      lesions.
AB  - Two cases of renal cell carcinoma, both of which underwent extensive spontaneous
      regression, are reported. The first occurred in a 56 year old man, forming a well
      circumscribed renal cortical nodule which contained only very occasional foci of
      viable renal cell carcinoma with areas of hyalinisation and calcification, and
      with metaplastic ossification. The second lesion was removed from an 82 year old
      man, comprising a cystic cavity containing necrotic debris with only occasional
      viable foci of classical renal cell carcinoma. Spontaneous regression of renal
      cell carcinoma is a rare but recognised entity. These two cases emphasise the
      important differential diagnoses: metastatic secondary carcinomas,
      xanthogranulomatous pyelonephritis, and infective granulomatous conditions of the
      kidney. The importance of adequate tissue sampling of all renal nodules cannot be
      overemphasised in the processing for examination of lesions within the kidney.

PMID- 9659252
TI  - The effect on patient management of temporary non-availability of
      immunofluorescence for renal biopsy reporting.
AB  - Delay in reporting the immunofluorescence findings on renal biopsies, owing to an
      interruption in supply of reagents, made possible a retrospective analysis of the
      effect of the lack of this information on patient management. Hospital case
      records of the 39 patients so affected were reviewed to determine what changes in
      their management took place after the immunofluorescence findings became
      available. The clinical, laboratory, and light microscopic findings in all except
      a case of pauci-immune crescentic glomerulonephritis allowed management decisions
      to be made that were not influenced by immunofluorescence findings. This was
      owing to correct prediction of the immunofluorescence findings, as in cases of
      IgA nephropathy presenting with recurrent haematuria; the adequacy of light
      microscopy in the interpretation of graft biopsies, in classifying lupus
      nephritis and in most cases of nephrotic syndrome; and the absence of entities
      identifiable only by immunofluorescence among these patients.

PMID- 9659253
TI  - Obstructive uropathy associated with myelomonocytic infiltration of the prostate.
AB  - A 72 year old man was diagnosed with chronic myelomonocytic leukaemia (CMML)
      according to the FAB group classification. He presented with symptoms of anaemia,
      urinary frequency, hesitancy, and nocturia. He was later admitted with acute
      urinary retention and acute renal failure, which resolved with treatment. A
      transurethral resection of the prostate was performed. Histological examination
      showed fibromuscular hyperplasia with dense infiltration by myelomonocytes which
      stained positively with chloroacetate esterase; immunohistochemical staining was
      positive for lysozyme, CD43, CD45, and CD68. Following treatment with oral
      etoposide he transformed to acute myeloid leukaemia and eventually died.
      Myelomonocytic infiltration of the prostate has not been reported before. This
      case extends the spectrum of disease previously recognised in CMML.

PMID- 9659254
TI  - Ulcerative colitis and perinuclear antineutrophil cytoplasmic antibodies.

PMID- 9659255
TI  - Facing up to the year 2000 computer bug.

PMID- 9659256
TI  - Why use the internet to teach pathology?

PMID- 9659257
TI  - ACP Broadsheet No 152: March 1998. Clinical implications of plasma homocysteine
      measurement in cardiovascular disease.
AB  - Plasma homocysteine is emerging as an important risk factor for cardiovascular
      disease. Measurement in clinical laboratories is feasible by several techniques,
      including HPLC. Of particular importance is the potential for treatment by
      dietary modification and vitamin supplements, particularly folic acid. The
      outcome of vitamin intervention on cardiovascular events is awaited with
      interest. If the role of homocysteine is confirmed then it may rival cholesterol
      in importance as a cardiovascular risk factor.

PMID- 9659258
TI  - Fine needle aspiration cytology in the investigation on non-Hodgkin's lymphoma.
AB  - AIMS: To assess the value of flow cytometry (FCM) in the diagnosis and
      classification of reactive lymphoid hyperplasia and malignant lymphoma by fine
      needle aspiration (FNA) cytology. METHODS: Forty six fine needle aspirates of
      lymphoproliferative disorders were examined by FCM as well as routine cytological
      assessment. An immunoglobulin light chain ratio (LCR) was calculated for
      clonality analysis. Additional immunophenotyping was performed in 15 cases.
      RESULTS: All 25 cases of reactive lymphoid hyperplasia were polyclonal by FCM
      (LCR < 2/1); 17 of 20 cases of B cell non-Hodgkin's lymphoma were monoclonal (LCR
      > 3/1). Analysis of cells based on size facilitated detection of small
      populations of clonal neoplastic cells. Analysis of CD5, CD10, and CD23
      expression by FCM facilitated subclassification of mantle cell lymphoma, small
      lymphocytic lymphoma, and some lymphomas of follicle centre cell origin. One case
      of T cell non-Hodgkin's lymphoma was correctly classified by FCM. CONCLUSIONS:
      FNA cytology is a reliable method for investigation of lymphoproliferative
      disorders. Although excision biopsy and histopathological examination remain the
      gold standard for primary diagnosis and classification of non-Hodgkin's lymphoma,
      FNA cytology with clonality analysis and immunophenotyping by FCM is useful for
      distinguishing reactive from neoplastic lymphoid populations, and can facilitate
      lymphoma classification.

PMID- 9659259
TI  - Fine needle aspiration cytology diagnosis of malignant lymphoma and reactive
      lymphoid hyperplasia.
AB  - AIMS: To assess the diagnostic accuracy of lymph node fine needle aspiration
      (FNA) cytology to distinguish reactive lymphoid hyperplasia from malignant
      lymphoma, and to evaluate the contribution of ancillary techniques applied to
      cytological material. METHODS: Two hundred and seventy seven consecutive lymph
      node FNA specimens reported to be consistent with reactive lymphoid hyperplasia
      (n = 213) or suggestive/diagnostic of malignant lymphoma (n = 64) were reviewed.
      Follow up data were obtained by case record review or by histological
      correlation. The value of immunocytochemistry, in situ hybridisation for
      immunoglobulin light chain mRNA, and polymerase chain reaction (PCR) towards the
      final clinicopathological diagnosis was assessed in 92, 61, and 45 cases,
      respectively. RESULTS: Sixty one of 67 lymphomas and 207 of 209 reactive lymph
      nodes were accurately diagnosed by FNA cytology. There were six false negative
      aspirates including three cases of follicular lymphoma, two cases of Hodgkin's
      disease, and one chronic lymphocytic leukaemia. Two FNA specimens considered
      suspicious of lymphoma proved reactive on histology or clinical follow up. One
      metastatic small cell carcinoma was wrongly diagnosed as lymphoma. Ancillary
      studies contributed to the correct diagnosis in most cases although occasional
      misleading results were obtained, particularly with PCR. CONCLUSIONS: FNA
      cytology accurately distinguished reactive lymphoid hyperplasia from malignant
      lymphoma in 97% of cases. However, occasional wrong diagnoses occurred owing to
      sampling error or misinterpretation. Ancillary studies can be applied to
      cytological samples and contribute to the diagnosis in most cases.

PMID- 9659260
TI  - Pseudoangiomatous hyperplasia of mammary stroma associated with gynaecomastia.
AB  - AIMS: To evaluate the prevalence of pseudoangiomatous hyperplasia of mammary
      stroma in gynaecomastia and its immunohistochemical profile in this setting.
      METHODS: Eighty eight cases of gynaecomastia recovered from the files of the
      department of pathology, Botucatu School of Medicine from 1976 to 1996 were
      studied. In the cases associated with pseudoangiomatous hyperplasia of mammary
      stroma, immunoreactivity for cytokeratins (CAM 5.2), vimentin, CD34, factor VIII
      related antigen, and the oestrogen and progesterone receptors were studied.
      RESULTS: Pseudoangiomatous hyperplasia of mammary stroma was found in 21 of 88
      cases of gynaecomastia (23.8%). In all cases, the cells lining the spaces were
      positive for vimentin, whereas CAM 5.2 and factor VIII related antigen were
      consistently negative. Nineteen of the 21 cases showed immunoreactivity for CD34.
      Ductal epithelial cells were positive for both the oestrogen receptor and the
      progesterone receptor, whereas stromal cells were negative. CONCLUSIONS:
      Pseudoangiomatous hyperplasia of mammary stroma was present in approximately one
      quarter of the cases of gynaecomastia. This immunohistochemical study confirms
      the mesenchymal origin of the stromal cells that line the pseudovascular spaces,
      as has been found in female cases of pseudoangiomatous hyperplasia of mammary
      stroma.

PMID- 9659261
TI  - Lymphocytic gastritis and coeliac disease: evidence of a positive association.
AB  - AIMS: To investigate the prevalence of lymphocytic gastritis in patients with
      coeliac disease. METHODS: Gastric biopsies from 70 patients with coeliac disease
      were examined by light microscopy for the presence of lymphocytic gastritis,
      defined as 25 or more intraepithelial lymphocytes/100 gastric columnar epithelial
      cells. RESULTS: Lymphocytic gastritis was found in seven cases. Positive cases
      had a mean of 32.1 intraepithelial lymphocytes/100 columnar cells, compared with
      a mean of 13.9 in negative cases, and 5.15 in noncoeliac controls. No differences
      were found for age, sex, gastric corpus or antrum, or degree of inflammation in
      the gastric lamina propria. All intraepithelial lymphocytes were of T cell
      lineage. Cases not showing lymphocytic gastritis did however show significantly
      increased gastric intraepithelial lymphocytes compared with non-coeliac controls.
      Eighteen of 70 cases were positive for Helicobacter pylori, and four of seven
      cases of lymphocytic gastritis were H pylori positive; no significant difference
      was observed between H pylori positive and negative patients. Three cases had
      concomitant ulcerative enteritis, of which none showed lymphocytic gastritis,
      while five cases had concomitant enteropathy associated T cell lymphoma, of which
      one showed lymphocytic gastritis. CONCLUSIONS: Lymphocytic gastritis occurred in
      10% of patients with coeliac disease. Cases without lymphocytic gastritis
      nevertheless showed increased gastric intraepithelial lymphocytes. Coeliac
      disease may on occasion be a diffuse lymphocytic enteropathy occurring in
      response to gluten. Lymphocytic gastritis outside coeliac disease may involve an
      immune response to luminal antigens, such as H pylori, not unlike the response to
      gluten in patients with coeliac disease.

PMID- 9659262
TI  - Quantitative histopathology can aid diagnosis in painful bladder syndrome.
AB  - AIMS: To define the pathology of painful bladder syndrome using a morphometric
      method. METHODS: Bladder biopsy specimens from 31 patients with painful bladder
      syndrome and 11 controls were stained and examined at x260 magnification with the
      aid of a 100 square counting grid. Random counts of the different tissues and
      inflammatory components were made to ascertain whether constant differences
      occurred that could be used to define the pathology of this uncommon condition.
      RESULTS: In the lamina propria of painful bladder syndrome specimens, a
      significant increase was seen in the concentration of lymphocytes, T cells, and
      blood vessels; a decrease was seen in the number of fibroblasts, and no change
      was seen in the number of mast cells and macrophages. B cells were sporadic. The
      basement membrane in these specimens showed significant discontinuity and there
      was increased collagen deposition in the underlying muscle when compared with
      controls. CONCLUSION: Painful bladder syndrome exhibits constant histological
      features that may be used to aid diagnosis in this uncommon condition. Simple
      numerical cell/tissue measurement of this kind is also useful when treatment
      trials are considered, because objective statistical analysis (pretreatment and
      post-treatment) is possible without the need for expensive and complicated
      equipment.

PMID- 9659263
TI  - Evaluation of the efficacy of 99mTc-Infecton, a novel agent for detecting sites
      of infection.
AB  - AIMS: To determine the sensitivity and specificity of 99mTc-Infecton (Infecton),
      a novel ciprofloxacin based imaging agent, in detecting sites of infection.
      METHODS: Ninety patients thought to be suffering from a variety of infections
      were administered 300-400 MBq of Infecton intravenously. Whole body images were
      taken one and four hours later. Appropriate specimens were taken for
      microbiological investigations. Statistical analysis was performed using a
      computer statistical package. RESULTS: Ninety eight Infecton images were
      produced. Forty one of these were positive, including three false positives,
      where the patients had non-infective conditions. Fifty seven negative images were
      obtained, of which 41 were true negatives and 16 were false negatives, having
      definite evidence of infection. Thus, Infecton imaging has a sensitivity of 70.3%
      and a specificity of 93.1% for detecting infective foci. The positive and
      negative predictive values were 92.6% and 71.9%, respectively. CONCLUSION:
      Infecton imaging is a new diagnostic tool that is specific for detecting sites of
      bacterial infection in the body. The high positive predictive value displayed by
      the technique is clinically important because a positive image strongly supports
      a diagnosis of bacterial infection. A negative result does not rule out an
      infection, and may be a result of previous or current antibiotic treatment and/or
      infection with organisms that do not take up Infecton. Infecton imaging has major
      advantages over well established imaging techniques, including radiolabelled
      leucocytes, and may prove to be a superior method for localising bacterial
      infections.

PMID- 9659264
TI  - Omeprazole may exert both a bacteriostatic and a bacteriocidal effect on the
      growth of Helicobacter pylori (NCTC 11637) in vitro by inhibiting bacterial
      urease activity.
AB  - AIMS: To assess the potential antibacterial effect of omeprazole, a benzimidazole
      proton pump inhibitor, on the growth of Helicobacter pylori in vitro and to
      evaluate the effect of this compound on bacterial urease activity. METHODS: The
      growth of H pylori was observed in liquid culture in the presence and absence of
      omeprazole (0.8 mg/ml). Urease activity was evaluated in aliquots removed from
      two hour cultures by monitoring the initial change in absorbency at 560 nm in the
      presence of 0.02% phenol red. RESULTS: The minimum inhibitory concentration of
      omeprazole against H pylori was 0.8 mg/ml. The concentration of omeprazole
      required to inhibit growth was dependent on inoculum density: omeprazole (0.8
      mg/ml) prevented growth from a 1 x 10(6) cfu/ml inoculum, but not from the higher
      inocula of 10(7) or 10(8) cfu/ml. This is the first study to demonstrate that
      omeprazole exerts a bacteriocidal effect against low bacterial densities and a
      bacteriostatic effect when bacterial density is high. When used at the onset of
      growth, this concentration of omeprazole has a bacteriocidal effect after four
      hours, although it exerts a bacteriostatic effect when added to cultures after
      the exponential phase. Bacterial urease activity is competitively inhibited by
      omeprazole in a dose dependent manner. CONCLUSION: The results suggest that
      omeprazole exerts both a bacteriocidal and a bacteriostatic effect against H
      pylori and competitively inhibits bacterial extracellular urease activity.

PMID- 9659265
TI  - CagA seropositivity associated with development of gastric cancer in a Japanese
      population.
AB  - BACKGROUND/AIMS: Infection with Helicobacter pylori strains possessing the cagA
      gene is associated with increased risk of gastric cancer of the intestinal type.
      The aims of this study were to investigate whether CagA seropositivity is
      associated with increasing risk of gastric cancer in a Japanese population that
      has a much higher incidence of gastric cancer than western populations. METHODS:
      Eighty one gastric cancer patients and 81 sex and age matched endoscopically
      evaluated controls were studied. Histologically, 62 cancers were of the
      intestinal type and 76 were early gastric cancer. Serum CagA IgG antibodies were
      assayed by enzyme linked immunosorbent assay (ELISA) using purified recombinant
      CagA protein as antigen. Polymerase chain reaction (PCR) analysis for cagA in H
      pylori isolates (n = 80) showed that the CagA ELISA had a sensitivity of 83.3%
      (controls) and 72.5% (cancers). RESULTS: CagA seropositivity was 60% (49 of 81)
      in cancer patients and 44% (36 of 81) in controls. The odds ratio for the risk of
      cancer if CagA seropositive was 1.93 (95% confidence interval (CI) 1.01 to 3.68;
      p < 0.05). In the 57 H pylori positive cancer patients and their matched H pylori
      positive controls, the odds ratio for the risk of cancer if CagA seropositive was
      2.2 (95% CI 1.04 to 4.65; p < 0.05). CONCLUSIONS: These results suggest that CagA
      seropositivity is associated with increased risk of gastric cancer in Japanese
      populations.

PMID- 9659266
TI  - Comparison of in situ hybridisation and polymerase chain reaction in the
      diagnosis of B cell lymphoma.
AB  - AIM: To compare the sensitivity of the detection of immunoglobulin light chain
      messenger RNA (mRNA) restriction by in situ hybridisation (ISH) and clonal
      immunoglobulin heavy chain gene rearrangements by polymerase chain reaction (PCR)
      in the diagnosis of B cell lymphoma. METHODS: Analyses were applied to formalin
      fixed, paraffin wax embedded, routine diagnostic specimens from cases with a
      provisional diagnosis of reactive lymph node (n = 23), B cell lymphoma (n = 21),
      and T cell lymphoma (n = 4). Nonisotopic ISH for kappa and lambda immunoglobulin
      light chain mRNA was performed using both fluorescein and digoxigenin labelled
      oligodeoxynucleotide probe cocktails. PCR was carried out on DNA extracted from
      sections using primers to framework 3 (Fr3) of the V segments and to conserved
      sequences from the J regions of the immunoglobulin heavy chain genes. RESULTS:
      All reactive lymph nodes showed a polyclonal pattern of light chain mRNA by ISH,
      although one showed an excess of kappa positive cells. Nineteen of 21 (90%) cases
      of B cell lymphoma showed light chain restriction, and a further case showed a
      vast excess of kappa positive cells. By PCR, 20 of 23 reactive nodes (87%) showed
      a polyclonal pattern. In 13 of 21 B cell lymphomas (62%) a clonal band was
      detected. CONCLUSION: In the diagnosis of B cell lymphoma in routinely processed
      diagnostic material ISH for light chain mRNA was more sensitive (90%) than PCR
      for heavy chain gene rearrangement using Fr3 and J region primers (62%).

PMID- 9659267
TI  - Effect of kidney function and disease status on urinary tissue factor
      measurements.
AB  - AIM: To investigate factors that influence urinary tissue factor (uTF)
      measurements: glomerular permeability and filtration, tubular function,
      haematuria, and urine bacterial growth. METHODS: uTF, protein creatinine index,
      glomerular filtration rate, retinol binding protein, N-acetyl-beta-D
      glucosaminidase (NAG) and urinary haemoglobin (uHb) were measured in patients
      with hypertension, diabetes mellitus and nephrotic syndrome (n = 342), tubulo
      interstitial disease (n = 50), and haematuria of uncertain cause (n = 50);
      measurements were also made in urine samples from healthy subjects for
      "simulated" haematuria (n = 6) and bacterial growth (n = 4) studies. RESULTS:
      There was a weak correlation of uTF with glomerular permeability and filtration
      (protein creatinine index and glomerular filtration rate) and with markers of
      tubular function (retinol binding protein and NAG). uTF concentrations were not
      affected by the presence of blood or bacteria in the urine sample. CONCLUSION:
      uTF concentrations are relatively stable. This is an important finding if the
      assay is to be used in clinical practice.

PMID- 9659268
TI  - Antimony in blood and urine of infants.
AB  - AIM: To establish a reference range for antimony in the serum and urine of
      infants in the first year of life. METHODS: 100 infants were selected randomly
      from the population. Each infant had a single blood and urine sample taken.
      Antimony was assayed using inductively coupled plasma mass spectrometry. RESULTS:
      The reference range for antimony in the serum of infants in the first year of
      life was established as 0.09-0.25 microgram/l. The upper 95% centile for urinary
      antimony, corrected for creatinine, in the same population was 2.6 ng/mg
      creatinine. There was a very weak correlation between the serum and urine
      concentrations. CONCLUSIONS: This study confirms the presence of low
      concentrations of antimony in the serum and urine of healthy infants.

PMID- 9659269
TI  - Histological identification of carcinoma in 21 gauge needle tracks after fine
      needle aspiration biopsy of head and neck carcinoma.
AB  - Six cancer resection specimens were thoroughly sectioned and microscopically
      examined at areas known to have been around 21 gauge fine needle aspiration (FNA)
      biopsy sites, in an attempt to identify needle tracks. All cases had an interval
      of not less than 10 days between FNA biopsy and surgery. Foci of tumour were
      identified histologically in needle tracks from two patients with carcinoma. This
      is the first instance, outside of experimental animal models, of histologically
      confirmed, viable tumour spread in FNA biopsy tracks. Although this complication
      is not common and is of unknown clinical significance, it is one that all
      clinicians who undertake FNA of malignant neoplasms should be aware of.

PMID- 9659271
TI  - A pseudo-cryptococcal artefact derived from leucocytes in wet India ink mounts of
      centrifuged cerebrospinal fluid.
AB  - Wet India ink mounts of cerebrospinal fluid (CSF) are useful in the laboratory
      diagnosis of cryptococcal meningitis. Pseudo-cryptococcal artefacts in such
      mounts have been attributed to leucocytes in CSF but their mode of formation has
      not been explained. This report describes the reproduction of such an artefact in
      cryptococcus free CSF-leucocyte mixtures that had been subjected to high speed
      centrifugation. The viscosity of DNA that could provide a morphological pseudo
      capsule, and the yellow-green fluorescence of the pseudo-capsular material on
      staining with acridine-orange, suggest that lymphocytic nuclear DNA, which
      possibly leaked out after damage to the lymphocyte membrane by centrifugation,
      was responsible for this artefact.

PMID- 9659270
TI  - Evidence of novel pathogenic pathways for the formation of antigastric
      autoantibodies in Helicobacter pylori gastritis.
AB  - Autoantibodies against gastric epithelial cells are detectable in up to 50% of
      patients with chronic, active Helicobacter pylori gastritis. Presence of
      autoantibodies against canalicular structures within human parietal cells
      (anticanalicular autoantibodies) correlate with gastric mucosa atrophy. It has
      been suggested, that molecular mimicry between H pylori and the host on the level
      of Lewis X and Lewis Y blood group antigens leads to these autoantibodies. This
      study aimed at analysing whether antigastric antibodies can be absorbed to Lewis
      X or Y positive H pylori strains. Sera from 14 H pylori infected patients with
      anticanalicular autoantibodies were effectively absorbed to H pylori.
      Immunohistochemical studies of the absorbed sera showed no decrease of
      antigastric autoreactivity. Pathogenic mechanisms other than molecular mimicry
      lead to the formation of antigastric autoantibodies, and epitopes other than
      Lewis antigens are the autoimmune targets.

PMID- 9659272
TI  - Measurement of haemoglobin using single drops of skin puncture blood: is
      precision acceptable?
AB  - The study aimed to investigate local concerns about clinically important
      discrepancies between repeat HemoCue haemoglobin measurements from single drops
      of blood. Two biomedical scientists and two health visitors each obtained a
      series of paired haemoglobin values by fingerprick sampling from healthy
      volunteers. Seven of 20 paired values obtained by health visitors and three of 20
      obtained by scientists from the first drop of blood forming at the puncture site
      differed by > or = 10 g/l; 11 of 20 paired values obtained by health visitors and
      one of 20 by the scientists from the fourth drop of blood differed by > or = 10
      g/l. After collecting and mixing a number of drops in EDTA tubes before analysis,
      seven of 40 paired values differed by > 5 g/l, and none by > 10 g/l. Pooling
      drops of blood before analysis improves precision of HemoCue haemoglobin
      measurement and allows users to achieve results comparable to those obtained by
      experienced laboratory staff. Measurement of haemoglobin from single drops of
      skin puncture blood should be discontinued.

PMID- 9659273
TI  - Unacceptably high site variability in postmortem blood alcohol analysis.
AB  - Blood alcohol concentration is a frequently requested test in forensic pathology.
      The variability of this value was studied by measuring the blood alcohol
      concentration from six sites in nine subjects at necropsy in whom alcohol was the
      implicated cause of death. There were small consistent differences in the blood
      alcohol concentrations between the sites in the nine subjects (p < 0.04).
      Calculation of the mean blood:vitreous humour alcohol concentration ratio (B:V
      ratio) showed that vitreous humour alcohol concentration most closely reflected
      the concentration at the femoral vein (B:V ratio = 0.94, r = 0.98), which is
      considered the optimal site for blood alcohol measurement. The correlation of
      left heart blood with femoral blood was lower compared with the other sites.
      There is a potential for an unacceptably large variation in the postmortem
      measurement of blood alcohol within each subject.

PMID- 9659274
TI  - Sample dilution to resolve mistaken identification of haemoglobin D as
      haemoglobin E using the variant automated system.
AB  - High performance liquid chromatography (HPLC) is increasingly being used to
      estimate variant haemoglobins. A case of haemoglobin S/D (HbS/D) is presented,
      which was misdiagnosed as haemoglobin S/E (HbS/E) by HPLC. The patient was a 22
      year old woman with sickle cell anaemia. Subsequent haemodilution by blood
      transfusion clearly elucidated the haemoglobin D peak on HPLC. Sample dilution
      experiments, using the pretransfusion sample, were done resulting in correct
      elution of the peak in the D window. Troubleshooting in similar problematic
      haemoglobin variant peaks seen on HPLC can be done by sample dilution.

PMID- 9659275
TI  - Biopsy specimen appearances of ischaemic gastritis in splanchnic arterial
      insufficiency.
AB  - A 74 year old man presented with a one month history of epigastric discomfort,
      anorexia, weight loss, and postprandial vomiting. The diagnosis of ischaemia was
      made on endoscopic biopsies from the stomach and duodenum. He was too ill for
      major vascular surgery and died eight days after admission. Postmortem
      examination confirmed the diagnosis of splanchnic arterial insufficiency caused
      by atheroma and thrombosis. Ischaemic gastritis is rare but could easily be
      missed in unrepresentative biopsy specimens. Prompt diagnosis with
      revascularisation surgery is the only hope for long term survival.

PMID- 9659276
TI  - Value of assessing parathyroid hormone-like activity in a case of extreme
      hypercalcaemia.
AB  - A previously well 70 year old woman was admitted to hospital following a three
      day history of vomiting and confusion. Her serum calcium was 6.58 mmol/l,
      phosphate 1.09 mmol/l, and alkaline phosphatase 91 iu/l. The mechanism of this
      hypercalcaemia was not obvious as there was no evidence of a primary malignancy,
      lymphadenopathy or hepatosplenomegaly. The calculation of indices of urinary
      excretion of calcium and phosphate suggested the presence of excessive
      parathyroid hormone (PTH) activity as the mechanism of hypercalcaemia. Plasma
      intact PTH, 25-hydroxycholecalciferol, and 1,25-dihydroxycholecalciferol were not
      raised suggesting the presence of PTH related peptide (rP). This led to a
      systematic search for a malignancy, which revealed the presence of a high grade B
      cell non-Hodgkin's lymphoma confined to the bone marrow. Plasma PTH-rP was
      subsequently shown to be raised confirming the interpretation of the initial
      urinary and calcium excretion indices. This case highlights the value of standard
      laboratory measurements such as urinary calcium and phosphate excretion in cases
      of hypercalcaemia of obscure aetiology, which can complement measurements of PTH
      and other calcitropic hormones.

PMID- 9659277
TI  - Neuroendocrine cell hyperplasia in colonic tissue used for long term augmentation
      cystoplasty.
AB  - A case is described of neuroendocrine cell hyperplasia in intravesical colonic
      mucosa, implanted previously during augmentation cystoplasty. The patient was a
      28 year old man born with posterior urethral valves, a non-functioning right
      kidney, and a poorly functioning dilated left kidney. The hyperplasia consisted
      of pure neuroendocrine acini and tubules within the lamina propria, separate from
      the normal intestinal glands. Adjacent intraepithelial colonic neuroendocrine
      cells were increased diffusely. Rectal biopsy and previous biopsies of
      intravesical colonic tissue contained normal neuroendocrine cell populations.
      Implantation of gut segments into the urinary tract predisposes to late
      neoplasia, but there is only one report of carcinoid tumour in uroenteric tissue.
      Intestinal neuroendocrine cell hyperplasia usually occurs diffusely rather than
      as aggregates, except when associated with adjacent carcinoid tumour. Both
      diffuse and nodular hyperplasia were present in this case, with an unusual and
      striking morphology. This is the first report of neuroendocrine cell hyperplasia
      in gastrointestinal tissue implanted into the urinary tract; this raises the
      possibility of a risk of late carcinoid tumour in uroenteric segments.

PMID- 9659278
TI  - Detection of parvovirus B19 in macerated fetal tissue using in situ
      hybridization.

PMID- 9659279
TI  - Use of histopathology in the practice of necropsy.

PMID- 9659280
TI  - Current perspectives on the pathogenesis of clinically non-functioning pituitary
      tumours.

PMID- 9659281
TI  - Prolactin receptor signal transduction in cells of the immune system.

PMID- 9659282
TI  - D-aspartic acid is implicated in the control of testosterone production by the
      vertebrate gonad. Studies on the female green frog, Rana esculenta.
AB  - In the present study we report the occurrence of D-aspartic acid (D-Asp) in the
      ovary of the green frog Rana esculenta and its putative involvement in
      testosterone production by the gonad. In the ovary, D-Asp concentrations undergo
      significant variations during the main phases of the sexual cycle. In spawning
      females (March), its concentration was low (2.5 +/- 1.1 nmol/g ovary) and during
      the post-reproductive period (June) it increased and reached its peak level (58.0
      +/- 10.1 nmol/g) in October. In that month, vitellogenesis occurs in a new set of
      ovarian follicles and continues until the next spring. The concentrations of D
      Asp in the ovary and of testosterone in the ovary and in the plasma were
      inversely correlated during the reproductive cycle: when endogenous D-Asp was low
      (March), testosterone was high (36.9 +/- 4.8 ng/g ovary; 23.1 +/- 2.76 ng/ml
      plasma) and, in contrast, when the D-Asp concentration was high (October), the
      testosterone concentration was low (0.86 +/- 0.21 ng/g ovary and 5.0 +/- 1.3
      ng/ml plasma). In vivo experiments, consisting of injection of D-Asp (2.0 mumol/g
      body weight) into the dorsal lymphatic sac of adult female frogs, demonstrated
      that this amino acid accumulates significantly in the ovary. After 3 h, moreover,
      it caused a decrease in testosterone level in the plasma of about 80%. This
      inhibition was reversible: within 18 h after the amino acid injection, as the D
      Asp concentration in the ovary decreased, the testosterone titre was restored in
      both ovary and plasma. In vitro experiments, conducted in isolated ovarian
      follicles, confirmed this phenomenon and identified these gonadal components as
      the putative D-Asp targets. Other amino acids (L-Asp, D-Glu, L-Glu, D-Ala and L
      Ala) used instead of D-Asp were ineffective. These findings indicate that D-Asp
      is involved in the control of androgen secretion by the ovary in this amphibian
      species, revealing a more complex system for control of this androgen synthesis
      than was previously believed to exist.

PMID- 9659283
TI  - Endothelin (ET)-1 and ET-3 inhibit estrogen and cAMP production by rat granulosa
      cells in vitro.
AB  - Endothelin (ET)-1 and ET-3, two peptides with a potent vasoconstrictive property,
      produce a variety of biological effects in different tissues by acting through
      two different receptors, the ET-1 selective ET(A) receptor and the non-selective
      ETB receptor. An increasing body of literature suggests that ET-1 acts as a
      paracrine/autocrine regulator of ovarian function. Indeed, ETB receptors have
      been identified in rat granulosa cells and ET-1 is a potent inhibitor of
      progesterone production. In contrast, inconsistent data have been reported about
      the role of ET-1 on estrogen production and the effects of ET-3 are not known.
      Therefore, the present study was undertaken to evaluate the effects of ET-1 and
      ET-3 on estrogen and cAMP production, and the receptor type involved. Given that
      prostanoids modulate ovarian steroidogenesis and that many actions of ETs are
      mediated by these compounds, we also evaluated whether the effects of ETs on
      estrogen and cAMP production might be prostanoid-mediated. ET-1, ET-3, and
      safarotoxin-S6c (SFX-S6c), a selective ETB receptor agonist, inhibited basal
      estrogen production by granulosa cells obtained from immature, estrogen-primed
      female rats, in a concentration-dependent manner. All three peptides were also
      capable of inhibiting the production of estrogen stimulated by a half-maximal (1
      mIU/ml) and a maximally stimulatory (3 mIU/ml) concentration of FSH, ET-1 and ET
      3 dose-dependently suppressed basal and FSH (1 mIU/ml)-stimulated cAMP
      production. ET-3 and SFX-S6c were significantly more potent than ET-1 in
      suppressing estrogen production, suggesting that this effect was not mediated by
      the ET(A) receptor. Indeed, BQ-123, a selective ET(A) receptor antagonist, did
      not influence the inhibitory effects of ET-1 and ET-3 on basal and FSH-stimulated
      estrogen release. To determine a possible involvement of prostanoids, we
      evaluated the effects of maximally effective concentrations of ET-1 and ET-3 on
      estrogen and cAMP production in the presence of indomethacin, a prostanoid
      synthesis inhibitor. This compound did not have any effect on the suppressive
      effects of ETs on basal or FSH (1 mIU/ml)-stimulated estrogen or cAMP production.
      In conclusion, ET-1 and ET-3 were able to inhibit estrogen and cAMP production by
      rat granulosa cells, indicating that the inhibitory effects of ETs on ovarian
      steroidogenesis are not limited to progesterone biosynthesis. This effect does
      not appear to be mediated by prostanoids or by the classical ET(A) and ETB
      receptors, at least under these experimental conditions.

PMID- 9659284
TI  - Transcription of (pro)renin mRNA in the rat adrenal cortex, and the effects of
      ACTH treatment and a low sodium diet.
AB  - Transcription of the (pro)renin gene in the adult rat adrenal gland was studied
      by non-isotopic in situ hybridization. In glands from control (untreated)
      animals, transcription was relatively sparse, and occurred mostly in the outer
      zona fasciculata. Treatment with ACTH increased the apparent signal in both the
      glomerulosa and in fasciculata zones. A low sodium diet initially enhanced the
      transcription signal specifically in the glomerulosa, but as the regime was
      extended from 5 days to more than 2 weeks, the signal was also increased
      dramatically in the zona reticularis. The results emphasize the potential
      importance of the intraglandular renin-angiotensin system, particularly under
      conditions of chronic stimulation. They also suggest that angiotensin II, as well
      as being the major regulator of the glomerulosa, may also have some role in inner
      adrenocortical zone functions.

PMID- 9659285
TI  - Chemotherapeutic agents used in the treatment of childhood malignancies have
      direct effects on growth plate chondrocyte proliferation.
AB  - Short stature is one of the most well recorded long term sequelae for adult
      survivors of childhood malignancies. It has become increasingly apparent that
      cytotoxic chemotherapy, as well as craniospinal irradiation, has a major impact
      on growth, but there are virtually no studies which explore the mechanisms by
      which these cytotoxic drugs affect growth. We have used an in vitro system to
      investigate the direct effects of a range of chemotherapeutic agents on the
      proliferative responses of rat tibial growth plate chondrocytes, both in
      suspension and monolayer culture. The glucocorticoids and purine anti-metabolites
      reduced chondrocyte proliferation both in monolayer and suspension cultures and
      this resulted from an increase in cell doubling times with a concomittant
      reduction in the numbers of S phase cells. DNA damaging agents (e.g. actinomycin
      D) were also able to reduce chondrocyte proliferation, both in monolayer and
      suspension culture. This, however, was the result of a cell cycle arrest and
      subsequent cell death. In our studies, methotrexate had no significant effect on
      the proliferative responses of the chondrocytes either in monolayer or suspension
      culture. These results indicate direct effects of a range of chemotherapeutic
      agents on the proliferative responses of growth plate chondrocytes. Both
      cytostatic and cytotoxic effects were observed although the impact of either the
      potential loss of cells from the proliferative pool during chondrocyte
      differentiation, or the reduction in the rate of chondrocyte turnover on long
      bone growth remains to be elucidated.

PMID- 9659286
TI  - Differential effects of retinoic acid on uncoupling protein-1 and leptin gene
      expression.
AB  - All-trans-retinoic acid (RA), one of the active metabolites of vitamin A, can
      increase the expression of uncoupling protein-1 (UCP1) gene. To determine whether
      RA stimulates brown adipose tissue (BAT) thermogenesis and modulates leptin gene
      expression in vivo, 6-month-old, vitamin-A sufficient, F344 x BN rats were
      administered a single dose of RA (7.5 mg/kg, i.p.) or the beta 3-adrenergic
      receptor (beta 3AR) specific agonist, CGP 12177 (0.75 mg/kg). Levels of UCP1 mRNA
      in BAT and leptin mRNA in perirenal white adipose tissue (WAT) were examined 5 h
      after treatment. mRNA levels of lipoprotein lipase (LPL) were also examined in
      BAT and perirenal WAT. Administration of CGP 12177 caused the expected increase
      in UCP1 mRNA levels. RA treatment also significantly increased UCP1 mRNA levels
      but to a lesser extent than CGP 12177. In contrast, there was no acute effect of
      RA on whole body oxygen consumption, one measure of BAT thermogenesis. Both CGP
      12177 and RA treatment decreased levels of leptin mRNA to a similar extent. RA
      treatment had no effect on mRNA levels of LPL in BAT or perirenal WAT. There were
      no changes in total DNA content, total protein content, or in the levels of beta
      actin mRNA in either BAT or perirenal WAT upon administration of RA or CGP 12177.
      Thus, the acute effects of RA paralleled the effects of the beta 3AR specific
      agonist, CGP 12177, on UCP1 and leptin gene expression. This involvement of RA in
      positive regulation of UCP1 mRNA and negative regulation of leptin mRNA suggests
      a contrasting role for RA in energy homeostasis.

PMID- 9659287
TI  - Effect of neonatal thyroidectomy on growth hormone secretion in the rat.
AB  - The influence of neonatal thyroidectomy (Tx) on GH production was investigated by
      means of Northern blot analysis. Tx resulted in a significant decrease in
      pituitary GH mRNA levels after 10, 15 and 20 days. The changes of pituitary GH
      mRNA were soon reflected in pituitary GH content. There was, however, no
      significant difference in pituitary GH mRNA levels and GH content between Tx and
      sham-operated rats at 5 days old. The pituitary GH cells were significantly
      decreased in number 15 and 20 days after Tx. These data suggest that GH mRNA is
      transcribed, independent of thyroid hormone, in the rat anterior pituitary gland
      during early neonatal life. In addition, the present study ascertained that GH
      dependence on thyroid hormone is acquired between the 5th and 10th day of
      neonatal life.

PMID- 9659288
TI  - Stage-related differences in rat seminiferous tubule contractility in vitro and
      their response to oxytocin.
AB  - Oxytocin (OT) is present in the mammalian testis and has been shown to play a
      role in the modulation of seminiferous tubule contractility and steroidogenesis.
      However, stage-specific effects of the peptide have not been previously
      investigated. In this study, computer-assisted analysis and time-lapse
      videomicrography were used to investigate basal contractility and the response to
      OT of seminiferous tubules at specific stages of the spermatogenic cycle. Adult
      rat testes were placed in fresh oxygenated DMEM F12 medium, decapsulated, and the
      tubules gently teased apart. Stages were identified by transillumination and a 10
      mm section of tubule at each of stages IV-V, VII-VIII and XIII-I was placed in a
      microslide chamber and perifused with medium. After a control period of 3 h, OT
      (2 nM) was given for 1 h, followed by another control period of 1 h. The
      experiment was repeated using tubules from different rats and data were analysed
      to give arbitrary units of tubule contractility. Contractility was observed in
      all the tubules studied and the contractile activity was shown to vary depending
      on the stage of the spermatogenic cycle. Mean basal contractility at stages VII
      VIII, the time when sperm are shed from the epithelium, was significantly lower
      than that at stages IV-V and XIII-I. The response of the tubules to OT was also
      stage-dependent, with the peptide producing the largest increases in contractile
      activity at stages VII-VIII and having no effect at stages IV-V. We postulate
      that these stage-specific differences in basal and OT-stimulated contractility
      may be important in co-ordinating the movement of developing germ cells towards
      the lumen of the seminiferous epithelium and in the process of spermiation.

PMID- 9659289
TI  - Insulin-releasing and insulin-like activity of Agaricus campestris (mushroom).
AB  - Agaricus campestris (mushroom) has been documented as a traditional treatment for
      diabetes. Here the administration of mushroom in the diet (62.5 g/kg) and
      drinking water (2.5 g/l) countered the hyperglycaemia of streptozotocin-diabetic
      mice. An aqueous extract of mushroom (1 mg/ml) stimulated 2-deoxyglucose
      transport (2.0-fold), glucose oxidation (1.5-fold) and incorporation of glucose
      into glycogen (1.8-fold) in mouse abdominal muscle. In acute 20 min tests, 0.25-1
      mg/ml aqueous extract of mushroom evoked a stepwise 3.5- to 4.6-fold stimulation
      of insulin secretion from the BRIN-BD11 pancreatic B-cell line. This effect was
      abolished by 0.5 mM diazoxide and prior exposure to extract did not affect
      subsequent stimulation of insulin secretion by 10 mM L-alanine, thereby negating
      a detrimental effect on cell viability. The effect of extract was potentiated by
      16.7 mM glucose, L-alanine (10 mM) and IBMX (1 mM), and a depolarising
      concentration of KCl (25 mM) did not augment the insulin-releasing activity of
      mushroom. Activity of the extract was found to be heat stable, acetone soluble
      and unaltered by exposure to alkali, but decreased with exposure to acid.
      Dialysis to remove components with molecular mass < 2000 Da caused a 40%
      reduction in activity. Sequential extraction with solvents revealed insulin
      releasing activity to be greatest in polar fractions. Lack of haemagglutinin
      activity with extract activity indicated that activity was unlikely to be due to
      a lectin-mediated event. These results demonstrate the presence of
      antihyperglycaemic, insulin-releasing and insulin-like activity in A. campestris.

PMID- 9659290
TI  - Rab3B is essential for GnRH-induced gonadotrophin release from anterior pituitary
      cells.
AB  - Gonadotrophin-releasing hormone (GnRH) induces the release of gonadotrophins via
      an increase in cytosolic Ca2+ concentration ([Ca2+]). Rab3B, a member of the
      small GTP-binding protein Rab family, is known to be involved in Ca(2+)-regulated
      exocytosis in pituitary cells. However, it is not known whether Rab3B functions
      in the physiological process regulated by GnRH in gonadotrophs. In this study
      using antisense oligonucleotide against Rab3B (AS-Rab3B) we determined that Rab3B
      is involved in GnRH-induced gonadotrophin release. Rab3B immunopositive cells
      were reduced in 24% of pituitary cells by AS-Rab3B. This treatment did not affect
      the population of gonadotrophs or the intracellular contents of gonadotrophins.
      However, AS-Rab3B significantly inhibited the total amount of basal and GnRH
      induced gonadotrophin released from pituitary cells. These results show that
      Rab3B is involved in basal and GnRH-induced gonadotrophins release but not the
      storage of gonadotrophins. Next, the changes in [Ca2+] and exocytosis in
      gonadotrophs treated with AS-Rab3B were compared among Rab3B-positive and 
      negative cells. The change in [Ca2+] was not different in the two groups, but
      exocytosis was significantly inhibited in Rab3B-negative cells. These results
      suggest that Rab3B is essential for GnRH-regulated exocytosis downstream of
      cytosolic Ca2+ in gonadotrophs.

PMID- 9659291
TI  - Effects of purinergic agonists on aromatase and gamma-glutamyl transpeptidase
      activities and on transferrin secretion in cultured Sertoli cells.
AB  - To study the role of extracellular nucleosides and nucleotides in the regulation
      of Sertoli cells, the effects of agonists which occupy A1 and P2 purinergic
      receptors on aromatase and gamma-glutamyl transpeptidase (gamma-GTP) activities
      and on transferrin secretion were tested. Sertoli cell treatment with purinergic
      agonists for a prolonged period of time (72 h) resulted in an increase in
      aromatase activity under basal conditions. In cultures stimulated with FSH,
      purinergic agonists counteracted the inhibitory effect on aromatase activity that
      long-term treatment with FSH promoted. The effects of prolonged treatments with
      purinergic agonists on the other two parameters of Sertoli cell function were
      less pronounced. Neither gamma-GTP activity nor transferrin secretion was
      modified under basal conditions. On the other hand, under conditions where cell
      differentiation was favored by FSH treatment, reductions in gamma-GTP activity
      and transferrin secretion were usually observed. The results obtained in dbcAMP
      stimulated cultures suggested that A1 agonists exert their regulatory function at
      the level of cAMP formation while P2 agonists act at a more distal point. The
      fact that morphological changes induced by FSH were reversed by both types of
      agonists, while those induced by dbcAMP were only abrogated by P2 agonists,
      supports this hypothesis. In summary, these results demonstrate that purinergic
      agonists may be important in the regulation of Sertoli cell function.

PMID- 9659292
TI  - Differential expression of IGF-I and IGF-binding protein-1 and -2 in periportal
      and perivenous zones of rat liver.
AB  - IGF-I has important roles in regulating growth and metabolism. Circulating IGF-I
      is bound to specific binding proteins (IGFBP-1 to -6), with hepatocytes
      containing IGF-I, IGFBP-1 and -2 mRNA. Although many hepatic proteins are
      regionally expressed in the liver acinus, no studies have reported zonation of
      IGF protein expression. In this study we investigated the pattern of hepatic mRNA
      for the IGF proteins, vs the previously reported pepriportal gradient of
      phosphoenolpyruvate carboxykinase (PEPCK) expression. In situ hybridisation was
      used to analyse IGF-I, IGFBP-1, -2 and PEPCK mRNA in female Sprague-Dawley rats
      fed diets containing low (6%), normal (21%) or high (35%) protein. We report for
      the first time that IGFBP-1 and -2 and IGF-I are differentially expressed in the
      liver acinus. In the normal- and high-protein groups, levels of IGFBP-1 mRNA were
      higher in the perivenous region, i.e. the opposite gradient to PEPCK, with a
      higher gradient of IGFBP-1 expression in the high-protein group. In contrast,
      IGFBP-2 had a similar pattern to PEPCK, and a periportal gradient of IGF-I mRNA
      was also seen in the low-protein group. Using computerised image analysis, levels
      of IGFBP-1 and -2 mRNA were elevated 2- and 10-fold respectively, in the low- vs
      normal-protein groups. The level of IGF-I mRNA was reduced to 65% of normal, with
      circulating IGF-I levels at 30% and insulin levels 39% of normal. These results
      demonstrate that hepatocytes are a heterogeneous population with respect to
      regulation of IGF proteins, having specific expression patterns dependent on the
      position of the hepatocyte within the liver acinus.

PMID- 9659293
TI  - Insulin-like growth factor-binding protein-3 protease activity in Snell normal
      and Pit-1 deficient dwarf mice.
AB  - Partial proteolysis of insulin-like growth factor-binding protein-3 (IGFBP-3)
      lowers its affinity for IGFs. Presumably, this leads to destabilization of the
      ternary IGF-IGFBP-3-acid-labile subunit complex in the circulation and an
      increased bioavailability of IGFs. We investigated the effect of GH on IGFBP-3
      proteolysis by comparing serum from normal mice and GH-deficient dwarf mice.
      While normal mouse serum degraded 125I-IGFBP-3, this activity declined with age.
      In contrast, serum from dwarf mice displayed strong proteolytic activity at all
      ages tested (up to 10 weeks). In dwarf mice of 4 weeks and older, this activity
      could not be inhibited by EDTA and 1,10-phenanthroline, indicating the presence
      of a divalent cation-independent protease. Prolonged treatment with GH (4 weeks)
      did not decrease the overall potency of the serum to degrade IGFBP-3, but
      partially restored the ability of EDTA to inhibit IGFBP-3 protease activity. GH
      deficiency therefore appears to induce a new kind of IGFBP-3 protease. Similarly,
      serum from hypophysectomized rats displayed enhanced IGFBP-3 protease activity
      compared with control rat serum. These results suggest that a protease induced
      under conditions of severe GH deficiency may contribute to making IGFs optimally
      available to the tissues.

PMID- 9659294
TI  - Cholinergic regulation of the rat adrenal zona glomerulosa.
AB  - Using histochemical and immunocytochemical methods, cholinergic nerve fibres were
      demonstrated in the rat adrenal cortex, primarily in the capsule and zona
      glomerulosa, and in the medulla. Some terminated among the glomerulosa cells or
      around blood vessels. Occasional fibres were also seen in the fasciculata, ending
      in islets of chromaffin tissue without ramifications on cortical cells. To
      clarify the role of cholinergic innervation, a microvolume perifusion system was
      used to study steroid production by the rat adrenal capsule-glomerulosa.
      Acetylcholine (ACh) itself had no reproducible effects; however, since variable
      amounts of endogenous ACh were present, the actions of antagonists were also
      studied. The M1 muscarinic receptor antagonist pirenzepine (10 and 100 microM)
      stimulated aldosterone secretion. This stimulation was abolished by co-incubation
      with carbachol, the M1 agonist McN A-343 and by atropine. We found that the
      action of pirenzepine was blocked by nifedipine (Ca2+ channel blocker),
      suggesting that pirenzepine (through release of endogenous ACh) provides an acute
      stimulus by enhancing Ca2+ inflow. Hemicholine, a choline uptake blocker, reduced
      the stimulatory effect of pirenzepine on steroid secretion, confirming that
      stimulation was of neural origin. Neither the non-selective muscarinic receptor
      antagonist atropine, the selective M1-M3 muscarinic receptor antagonist 4-DAMP,
      nor the selective M2 muscarinic receptor antagonist methoctramine influenced
      aldosterone output. Receptor-binding studies revealed the existence of M3
      receptors in capsule-glomerulosa homogenates. We conclude that pirenzepine acts
      on presynaptic M1 autoreceptors to increase spontaneous ACh release from varicose
      axon terminals that lie in close proximity to the glomerulosa cells. In turn ACh
      may thus stimulate steroidogenesis acutely through M3 receptors. These results
      support the concept of a direct cholinergic influence on zona glomerulosa
      function in the rat.

PMID- 9659295
TI  - Leydig cell apoptosis in the rat testes after administration of the cytotoxin
      ethane dimethanesulphonate: role of the Bcl-2 family members.
AB  - Ethane dimethanesulphonate (EDS) is cytotoxic to Leydig cells in the adult rat.
      To investigate the role and regulation of apoptosis in the Leydig cell, EDS (100
      mg/kg i.p.) was administered to adult male rats and the testes examined 6, 12,
      18, 24, 48 and 72 h later. Numbers of Leydig cells, identified by 3 beta
      hydroxysteroid dehydrogenase immuno-histochemistry started to fall by 12 h after
      EDS injection and were almost undetectable by 72 h. Apoptotic cells in the
      interstitium, visualised by in situ end labelling of DNA, increased in number to
      reach a maximum 24 h after injection of EDS, and were undetectable by 72 h. In
      many tissues the apoptosis-related gene products act in cohort: Bcl-2 and Bcl-xl
      promoting survival of a cell, whilst Bax promotes cell death often positively
      regulated by the tumour-suppressor gene p53. Western blot analysis showed that:
      (1) Bcl-2 and p53 were absent from interstitial Leydig cells but were expressed
      in the seminiferous tubules. (2) Bax protein although expressed in the
      interstitium was not present in the Leydig cells. (3) Bcl-xl in Leydig cells was
      transiently increased after EDS. In conclusion, EDS kills Leydig cells by
      apoptosis; however the control of Leydig cell death does not involve p53 or the
      Bcl-2 family members but may require other gene products yet to be identified.

PMID- 9659297
TI  - Mutation and expression analysis of the cyclin-dependent kinase inhibitor gene
      p27/Kip1 in pituitary tumors.
AB  - By regulating cyclin-cyclin-dependent kinase (CDK) complex activity, individual
      CDK inhibitors (CDKIs) are potential tumor suppressors. One of the CDKIs,
      p27/Kip1, binds to a variety of CDK-cyclin complexes. A link between loss of
      p27/Kip1 function and development of pituitary tumors was suggested by the
      formation of pituitary tumors in almost all mice with germline deletion of the
      p27/Kip1 gene. However, genetic aberrations in the p27/Kip1 locus have not been
      analyzed in human pituitary tumors. We investigated eighteen non-functioning and
      GH-secreting pituitary tumor samples for p27/Kip1 mutations by single-strand
      conformational polymorphism (SSCP) following PCR. We found five abnormally
      migrating samples on the PCR-SSCP analysis. The sequence of these samples
      revealed a polymorphism of codon 109 (Val-->Gly), which has been previously
      described. No other structural changes of p27/Kip1 were found in these pituitary
      tumors within the coding region. In addition, no difference in p27/Kip1 protein
      levels in pituitary tumor tissues compared with normal pituitary tissues was
      demonstrated by immunostaining. These data suggest that both p27/Kip1 mutations
      and decreases in p27/Kip1 protein levels are infrequent in the development of
      pituitary tumors.

PMID- 9659296
TI  - Regulation of IGF binding protein synthesis by a bovine mammary epithelial cell
      line.
AB  - IGF-I has been proposed as a key regulator of mammary epithelial cell (MEC)
      growth and differentiation. As IGF-I bioactivity is modulated by specific, high
      affinity binding proteins (IGFBP), the forms of IGFBP that are secreted by the
      bovine MEC line, MAC-T, were identified. Media conditioned by MAC-T cells
      contained four forms of IGFBP that were identified, by western blotting with
      specific antibodies, as IGFBP-2, -3, -4 and -6. The amounts of IGFBP-3 in
      conditioned media were relatively low under basal conditions when analyzed by
      ligand blotting with 125I-IGF-II, but were increased dramatically relative to
      serum-free controls by exposure to IGF-I (100 ng/ml) or IGF-II (100 ng/ml) for 24
      h. These increases in IGFBP-3 protein corresponded with dose-dependent increases
      in IGFBP-3 mRNA, with IGF-II eliciting a smaller response than was elicited by
      IGF-I at each concentration. Leu-IGF-I, which has reduced affinity for the IGF-I
      receptor but normal affinity for IGFBPs, failed to increase IGFBP-3 protein and
      mRNA levels, whereas B-chain IGF-I (normal affinity for the receptor but reduced
      affinity for IGFBPs) elicited the response, thus implying an IGF-I receptor
      mediated event. Time-course studies indicated that IGFBP-3 mRNA was increased
      fourfold by 3 h of IGF-I treatment, with maximal increases of eightfold above
      serum-free controls observed between 8 and 13 h of treatment. By 24 h of
      treatment, IGFBP-3 mRNA levels had declined and were approximately threefold
      above controls in cells exposed to IGF-I. Amounts of messenger RNA of IGFBP-6 and
      IGFBP-2 were not increased by IGF treatment. However, retinoic acid (10(-6) M)
      stimulated both IGFBP-2 and IGFBP-6 protein and mRNA levels, but it decreased
      IGFBP-3 mRNA levels relative to controls. The combination of retinoic acid plus
      IGF-I had no additional effect on IGFBP-6 or -2 above that observed with retinoic
      acid alone, whereas IGF-I together with retinoic acid attenuated the decrease in
      IGFBP-3 observed with retinoic acid alone. Protein kinase A-mediated pathways
      were also shown to alter IGFBP synthesis. Forskolin, which increases cAMP,
      increased IGFBP-3 protein and mRNA levels. The combination of IGF-I plus
      forskolin resulted in greater increases in both protein and mRNA than were
      observed with either treatment alone. In contrast, forskolin decreased IGFBP-6
      mRNA relative to controls, but had no effect on IGFBP-2. The decrease in IGFBP-6
      was less marked when cells were treated with a combination of IGF-I and
      forskolin. Forskolin had no effect on IGFBP-2 mRNA levels. In summary, the
      ability of IGF-I specifically to regulate IGFBP-3 synthesis represents a
      mechanism whereby IGF-I may regulate its own bioactivity. In addition, the
      differential regulation of IGFBP-2, -3 and -6 by retinoic acid (which inhibits
      proliferation) and IGF-I (which stimulates proliferation) suggests that these
      forms of IGFBP have different roles in regulating mammary epithelial cell
      physiology.

PMID- 9659298
TI  - A spontaneous induction of fetal membrane prostaglandin production precedes
      clinical labour.
AB  - Fetal membranes from term human pregnancies produce prostaglandins, and may
      respond to bacterial endotoxin or interleukin-1 beta (IL-1 beta) with increased
      prostaglandin E2 (PGE2) production. The effects of endotoxin persisted for up to
      24 h, whereas those of IL-1 beta were maximal 4-8 h after addition. The maximum
      levels of PGE2 (200-350 pg/ml) were similar in all experiments, and were
      independent of the stimulus used. Not all tissues responded to these stimuli;
      those which did not had basal levels of PGE2 production of 200-350 pg/ml, which
      was not further increased by endotoxin or IL-1 beta. The basal production from
      these tissues was therefore similar to the maximal production from those tissues
      which responded to endotoxin or IL-1 beta. The high basal production of PGE2 was
      attributed to prior in vivo activation of the membranes such that PGE2 synthesis
      could not be further stimulated in vitro. Overnight pretreatment with aspirin
      decreased basal PGE2 production from these activated membranes to < 100 pg/ml/4 h
      during subsequent culture in aspirin-free medium. Both endotoxin and IL-1 beta
      increased PGE2 production from the activated aspirin-pretreated membranes during
      this culture time, but this was transient as after 12 h of culture basal PGE2
      production rose to over 200 pg/ml despite aspirin pretreatment.

PMID- 9659299
TI  - Impaired membrane translocation of thrombin stimulated PKC epsilon by high
      glucose.
AB  - Hyperglycaemia is known to cause endothelial dysfunction and to promote diabetic
      angiopathy. Therefore, this study was designed to evaluate the effect of long
      term incubation (16 +/- 1 days) in 30 mM vs 5 mM glucose on ligand induced
      translocation of protein kinase C (PKC) in paired cultures of individual isolates
      of human umbilical vein endothelial cells (HUVECs). Cells were stimulated with
      increasing concentrations of thrombin (0.01, 0.1, 1, 10 and 100 nM) for 30
      seconds in the presence of 5 mM and 30 mM glucose, respectively, and analyzed by
      immunoblotting for PKC-isoforms alpha and epsilon. Stimulation by thrombin of
      confluent cultures displayed a concentration dependent rise in membrane bound PKC
      alpha and epsilon. Translocation of PKC alpha by thrombin remained unaffected by
      high versus normal ambient glucose, whereas translocation of PKC epsilon in cells
      grown in 30mM glucose was reduced at maximal thrombin concentrations (area under
      the curve, AUC: 90.4 +/- 7% of control cells; p < 0.008; n = 6) versus control
      cultures kept in 5mM glucose. In the identical isolates translocation of PKC
      epsilon was not reduced by 30 mM mannitol used as osmotic control. No change was
      induced by long term incubation of resting cells with 30 mM vs 5 mM glucose as to
      total and membrane bound PKC alpha or PKC epsilon. The obtained data suggest
      modulation by 30 mM glucose of ligand induced PKC translocation in an isoform
      specific manner, whereas subcellular distribution of PKC isoforms in the absence
      of thrombin stimulation remains unaffected by 30 mM glucose.

PMID- 9659300
TI  - Healing powers.

PMID- 9659301
TI  - People with learning disabilities as offenders or alleged offenders in the UK
      criminal justice system.

PMID- 9659302
TI  - Does 'healing' benefit patients with chronic symptoms? A quasi-randomized trial
      in general practice.
AB  - This study was designed to examine the effects of a healer seeing chronically ill
      patients in a large semirural practice. The 57 patients were allocated
      alternately either to receive ten weekly healing sessions or to become waiting
      list controls. Two weeks after completion of 'healing' 22 (81%) of the 27 study
      patients thought their symptoms had improved and 15 of these thought they had
      improved substantially. Study patients scored better than controls on both
      measures of symptoms (P < 0.05, P < 0.01), on anxiety and depression ratings (P <
      0.01, P < 0.05) and on general function measured by the Nottingham Health Profile
      (P < 0.01). Treatment differences were still evident three months later for one
      of the measures of symptom change (P < 0.05) and for both anxiety and depression
      ratings (P < 0.01, P < 0.05). The percentages of natural killer cells (CD16,
      CD56) did not change greatly in either group. These results suggest that healing
      may be an effective adjunct for the treatment of chronically ill patients
      presenting in general practice. They do not distinguish between any specific
      effects of spiritual healing and non-specific effects such as relaxation; for
      further investigation, randomized controlled trials will be needed.

PMID- 9659303
TI  - Management of lipids in the elderly.

PMID- 9659304
TI  - Diarrhoeal disease: a world-wide problem.

PMID- 9659305
TI  - Monitoring and management of acidosis in calf diarrhoea.

PMID- 9659306
TI  - Four strategies for negotiated care.

PMID- 9659307
TI  - Consumer health information on the Internet.

PMID- 9659308
TI  - Misoprostol and attempted self-induction of abortion.

PMID- 9659309
TI  - Acute hypertriglyceridaemic pancreatitis in a pregnant Indian: a new lipoprotein
      lipase gene mutation.

PMID- 9659310
TI  - Facial lupus erythematosus profundus in a 9-year-old boy.

PMID- 9659311
TI  - Minds and hearts: themes in the life of Gleb von Anrep.

PMID- 9659312
TI  - Paintress, princess and physician's paramour: poison or perforation?

PMID- 9659313
TI  - Georgiana, Duchess of Devonshire, and Princess Diana: a parallel.

PMID- 9659314
TI  - Disorders of mythopoiesis.

PMID- 9659315
TI  - Early management of the severely injured patient.

PMID- 9659316
TI  - Confusion of roles in the National Health Service.

PMID- 9659317
TI  - Treatment of Zollinger-Ellison syndrome.

PMID- 9659318
TI  - Is alcohol good for you?

PMID- 9659319
TI  - Transient ptosis and miosis after a rugby injury.

PMID- 9659321
TI  - Culture and medicine.

PMID- 9659322
TI  - Direct ophthalmoscopy versus slit lamp biomicroscopy in diagnosis of the acute
      red eye.
AB  - The causes of red eye range from trivial to life-threatening, and many general
      practitioners are uncertain of their ability to diagnose them with the aid of an
      ophthalmoscope. We tested the hypothesis that, in the assessment of a patient
      with red eye, a doctor using a slit lamp biomicroscope would not differ in
      diagnostic accuracy from a doctor using a direct ophthalmoscope. A cross-over
      study was conducted in 98 patients newly attending an eye casualty department.
      71% of diagnoses agreed exactly, and all potentially sight-threatening lesions
      were either diagnosed correctly or managed appropriately by doctors using an
      ophthalmoscope. We conclude that the initial diagnosis and management of patients
      with an acute red eye is not prejudiced by the lack of a slit lamp biomicroscope.

PMID- 9659323
TI  - Digital radiology in skeletal trauma: assessment of casualty officers'
      performance.
AB  - Radiographic images can now be produced without the requirement of film
      processing and development, and can be displayed rapidly on a computer monitor.
      We assessed junior doctors' performance in interpreting images from 25 patients
      being investigated for possible fracture and also compared the diagnostic
      abilities of casualty officers with those of radiology specialist registrars. For
      interpretation of images viewed at a workstation or as filmed laser images,
      respectively, sensitivities were 75% and 78%, and specificities were 65% and 76%.
      These differences were not significant. There was a tendency for radiology
      specialist registrars to be less specific when reviewing images at a workstation.
      The demonstration that there is no loss in diagnostic quality when casualty
      officers interpret fracture images in a purely digitally acquired and viewed
      format forms a robust basis for economic evaluation of the technology.

PMID- 9659324
TI  - Exacerbation of atopic dermatitis after bacillus Calmette-Guerin vaccination.
AB  - In two children with atopic dermatitis, routine vaccination with bacillus
      Calmette-Guerin (BCG) was followed by severe exacerbation of skin disease. If the
      sequence is cause and effect, a possible mechanism is stimulation of a Th2
      lymphocyte cytokine profile by the vaccine, with migration of activated
      lymphocytes to inflamed skin. In children with active atopic dermatitis, BCG
      vaccination is best deferred until remission.

PMID- 9659325
TI  - Nutritional management of Crohn's disease in childhood.

PMID- 9659326
TI  - Death and dying--a Muslim perspective.

PMID- 9659327
TI  - Psychosexual care in a multi-ethnic society.

PMID- 9659328
TI  - Childhood headaches caused by occult sinusitis.

PMID- 9659329
TI  - Thioridazine, diarrhoea and torsades de pointe.

PMID- 9659330
TI  - Arteriovenous malformation of the whole small bowel--a therapeutic dilemma.

PMID- 9659331
TI  - Modified sigmoidoscopy biopsy forceps.

PMID- 9659332
TI  - Myxoedematous madness and The Citadel.

PMID- 9659333
TI  - Technological medicine and the elderly: who cares?

PMID- 9659334
TI  - Medical journals on the World Wide Web.

PMID- 9659335
TI  - Palpitation: brain, heart, and 'spirits' in the seventeenth century.

PMID- 9659336
TI  - Modern medicine and the Hippocratic doctors of ancient Greece.

PMID- 9659337
TI  - Is Hippocrates obsolete?

PMID- 9659338
TI  - Is alcohol good for you?

PMID- 9659339
TI  - Thyroid click.

PMID- 9659340
TI  - Early British surgical instruments.

PMID- 9659341
TI  - Tropical ulcers and diphtheria.

PMID- 9659342
TI  - Transmission of plague.

PMID- 9659343
TI  - Unintentional gluten ingestion in celiac patients.

PMID- 9659344
TI  - Insensitivity of the CLOtest for H. pylori, especially in the elderly.

PMID- 9659345
TI  - The relevance of luminal release is doubtful.

PMID- 9659346
TI  - Histamine H3 receptors and gastric acid secretion.

PMID- 9659347
TI  - Gene therapy for cystic fibrosis: what message for the recipient?

PMID- 9659348
TI  - Pneumococcal serotypes and their clinical relevance.

PMID- 9659349
TI  - Dietary intake of antioxidant (pro)-vitamins, respiratory symptoms and pulmonary
      function: the MORGEN study.
AB  - BACKGROUND: A study was undertaken to investigate the relationships between the
      intake of the antioxidant (pro)-vitamins C, E and beta-carotene and the presence
      of respiratory symptoms and lung function. METHODS: Complete data were collected
      in a cross sectional study in a random sample of the Dutch population on 6555
      adults during 1994 and 1995. Antioxidant intake was assessed by a semi
      quantitative food frequency questionnaire and respiratory symptoms (cough,
      phlegm, productive cough, wheeze, shortness of breath) were assessed by a self
      administered questionnaire. Prevalence odds ratios for symptoms were calculated
      using logistic regression analysis. Linear regression analysis was used for
      forced expiratory volume in one second (FEV1) and forced vital capacity (FVC).
      The results are presented as a comparison between the 90th and 10th percentiles
      of antioxidant intake. RESULTS: Vitamin C intake was not associated with most
      symptoms but was inversely related with cough. Subjects with a high intake of
      vitamin C had a 53 ml (95% CI 23 to 83) higher FEV1 and 79 ml (95% CI 42 to 116)
      higher FVC than those with a low vitamin C intake. Vitamin E intake showed no
      association with most symptoms and lung function, but had a positive association
      with productive cough. The intake of beta-carotene was not associated with most
      symptoms but had a positive association with wheeze. However, subjects with a
      high intake of beta-carotene had a 60 ml (95% CI 31 to 89) higher FEV1 and 75 ml
      (95% CI 40 to 110) higher FVC than those with a low intake of beta-carotene.
      CONCLUSIONS: The results of this study suggest that a high intake of vitamin C or
      beta-carotene is protective for FEV1 and FVC compared with a low intake, but not
      for respiratory symptoms.

PMID- 9659350
TI  - Effect of inhaled L-arginine on exhaled nitric oxide in normal and asthmatic
      subjects.
AB  - BACKGROUND: Nitric oxide (NO) plays an important part in the regulation of many
      physiological functions and may also be involved in several pulmonary diseases.
      Endogenous NO is synthesised by different isoforms of NO synthase (NOS) from L
      arginine. METHODS: The effect of inhaled L-arginine 0.75 g (six normal and six
      asthmatic subjects), 1.5 g (six normal and six asthmatic subjects), and 3 g
      (seven normal and six asthmatic subjects) has been studied in a double blind
      placebo controlled, randomised, parallel group design study. In addition, the
      effect of a single dose (3 g) of inhaled L-alanine has been assessed in five
      normal and five asthmatic subjects. RESULTS: L-arginine increased exhaled NO in a
      dose-dependent fashion with a maximum at 60 minutes. The cumulative effect of L
      arginine (3 g) on NO in asthmatic subjects, expressed as the area under the curve
      in arbitrary units (au) and compared with the effect of placebo (0.9% NaCl), was
      significantly higher (mean 0.11 au; 95% confidence interval (CI) 0.03 to 0.19)
      than in normal subjects (0.012 au; 95% CI 0.002 to 0.022). There was a negative
      correlation (r = -0.72) between the increase in exhaled NO and the fall in forced
      expiratory volume in one second (FEV1) (0.034 au, 95% CI 0.030 to 0.038) after 3
      g L-arginine in asthmatic subjects. Inhalation of 3 g of L-alanine produced a
      similar reduction in FEV1 (0.033 au, 95% CI 0.007 to 0.059) but no significantly
      different changes in exhaled NO (0.017 au, 95% CI 0.001 to 0.039) compared with
      placebo (0.020 au, 95% CI 0.001 to 0.042). CONCLUSIONS: An increase in the amount
      of substrate for NOS increases the formation of endogenous NO. L-arginine may
      have therapeutic potential in diseases in which there is defective production of
      NO, but in asthma it may amplify the inflammatory response in the airways.

PMID- 9659351
TI  - Geographical distribution of tuberculosis notifications in national surveys of
      England and Wales in 1988 and 1993: report of the Public Health Laboratory
      Service/British Thoracic Society/Department of Health Collaborative Group.
AB  - BACKGROUND: The geographical distribution of tuberculosis in England and Wales
      and changes since 1983 were examined using data from the 1988 and 1993 national
      surveys of tuberculosis notifications. METHODS: Notification rates for England
      and Wales in 1988 and 1993 were calculated for geographical areas using Office
      for National Statistics (ONS) mid year population estimates. Those for the
      standard regions and the Greater London boroughs were calculated for the main
      ethnic groups. Those for the counties and local authorities were calculated for
      all ethnic groups combined. These were compared using data from the 1983 national
      survey as a baseline. RESULTS: Wide regional variations in notification rates
      persist with Greater London having the highest rates. Rates in the ethnic group
      from the Indian subcontinent (ISC) were high in all regions, whilst those of the
      white ethnic group varied fourfold. Twenty seven of the 33 London boroughs showed
      increased rates in 1993 compared with 1988. In general, those local authority
      areas with high rates had high proportions of notifications in individuals of ISC
      ethnic origin, emphasising the continuing important contribution of ethnic
      minority groups to local tuberculosis rates. The number of local authority areas
      with notification rates four times the national average increased, but the number
      of areas with low or zero rates increased even more. CONCLUSIONS: The
      distribution of tuberculosis in England and Wales continues to vary markedly by
      geographical area. The distribution is becoming increasingly polarised with a
      growth in the number of areas with very high rates of notifications and a greater
      increase in the number of areas with very few notifications. Patients from ethnic
      minorities continued to contribute a substantial and increasing proportion of all
      reported tuberculosis cases in most regions in 1988 and 1993. These findings have
      important implications for the provision of tuberculosis services in England and
      Wales.

PMID- 9659352
TI  - Non-tuberculous mycobacteria in cystic fibrosis.
AB  - BACKGROUND: The clinical significance of the presence of non-tuberculous
      mycobacteria in the sputum of patients with cystic fibrosis is unclear. A
      retrospective case-control study was performed to assess possible risk factors
      for non-tuberculous mycobacteria and its impact on clinical status in patients
      with cystic fibrosis. METHODS: The records of all patients attending the Leeds
      cystic fibrosis clinics who were positive for non-tuberculous mycobacteria were
      examined. Each case was matched with two controls for sex, age, and respiratory
      function at the time of the first non-tuberculous mycobacteria isolate. Details
      of respiratory function, nutritional status, antibiotic and corticosteroid
      therapy, Shwachman-Kulczycki (S-K) score, Northern chest radiographic score, and
      the frequency of isolation of other bacteria and fungi were collected from two
      years before to two years after the first non-tuberculous mycobacteria isolate.
      The patients' genotype and the presence of diabetes mellitus were also recorded.
      RESULTS: Non-tuberculous mycobacteria were isolated from 14 patients out of a
      cystic fibrosis population of 372 (prevalence = 3.8%). No significant effect of
      non-tuberculous mycobacteria was seen on respiratory function, nutritional
      status, or S-K score. There was a significant association with the number of
      intravenous antibiotic courses received before the first isolate with cases
      receiving, on average, twice as many courses as controls (cases 6.64, controls
      2.86, 95% CI for difference 1.7 to 5.9). No significant difference was seen
      between cases and controls for Northern scores, previous steroid therapy, or the
      incidence of diabetes mellitus. CONCLUSIONS: Non-tuberculous mycobacteria
      infection in patients with cystic fibrosis is uncommon and its clinical impact
      appears to be minimal over a two year period. Frequent intravenous antibiotic
      usage is a possible risk factor for colonisation with non-tuberculous
      mycobacteria.

PMID- 9659353
TI  - Preventive effect of erythromycin on experimental bleomycin-induced acute lung
      injury in rats.
AB  - BACKGROUND: Erythromycin has been reported to have an inhibitory effect on
      chronic inflammatory airway disease and chronic infiltration of neutrophils into
      the airway. Bleomycin (BLM) often induces interstitial lung fibrosis following
      acute lung injury. A study was undertaken to investigate the effects of
      erythromycin (EM) on experimental bleomycin-induced acute lung injury in rats.
      METHODS: Bleomycin-induced lung injury was assessed by light microscopic
      examination, measurement of neutrophil elastase activity and of the interleukin 8
      (IL-8) content in bronchoalveolar lavage (BAL) fluid. The potential inhibitory
      effect of erythromycin was assessed by overall comparison of erythromycin
      untreated (BLM alone), concurrently treated (BLM + EM), and pretreated (BLM + pre
      EM) groups. RESULTS: The neutrophil count and concentration of neutrophil-derived
      elastase in BAL fluid were significantly different in the three groups. The
      morphological changes of lung injury were also less extensive in rats pretreated
      with erythromycin. However, these protective effects were not marked in the group
      concurrently treated with erythromycin. Moreover, the concentration of IL-8 in
      the BAL fluid tended to be less in the erythromycin treated groups; however,
      there were no significant differences between the bleomycin-treated groups.
      CONCLUSION: Erythromycin exhibits a prophylactic effect on acute lung injury
      induced by intratracheal administration of bleomycin, which is possibly
      associated with a downregulation of neutrophil-derived elastase.

PMID- 9659354
TI  - Videothoracoscopic treatment of oesophageal leiomyoma.
AB  - BACKGROUND: Oesophageal leiomyomas are usually so easily removed that thoracotomy
      seems out of proportion and thoracoscopic removal is therefore highly desirable.
      METHODS: Out of a total of 1003 thoracoscopic operations undertaken between July
      1991 and December 1996, seven patients underwent thoracoscopic removal of
      oesophageal leiomyoma. All of them had been preoperatively studied by
      oesophagogastroscopy and computed tomographic scanning of the chest which had
      confirmed the presence of a lesion with benign features. The surgical technique
      required intubation with a double lumen tube. Operative access was gained through
      the right chest via three ports and a small utility thoracotomy in the
      inframammary sulcus. The mean operating time was 120 minutes. RESULTS: Conversion
      to open thoracotomy was necessary in one case with a very large horseshoe-shaped
      leiomyoma which was firmly adherent. The mean postoperative hospital stay was
      seven days. No intraoperative deaths or postoperative complications occurred.
      CONCLUSIONS: The simplicity and safety of the thoracoscopic approach, combined
      with reduced surgical trauma and postoperative pain and functional and cosmetic
      advantages, make this technique the approach of choice for the removal of
      oesophageal leiomyomas.

PMID- 9659355
TI  - Preferential binding of lysozyme to elastic fibres in pulmonary emphysema.
AB  - BACKGROUND: Lysozyme is increased in inflammatory reactions and is a component of
      the extracellular matrix, but its possible role in lung diseases such as
      emphysema and interstitial fibrosis has not been investigated. METHODS: To
      characterise differences in lysozyme content among normal, emphysematous, and
      fibrotic human lungs, tissue sections obtained from necropsy specimens were
      immunostained with rabbit polyclonal anti-human lysozyme antibody using the
      labelled streptavidin-biotin peroxidase method. The immunostained sections were
      evaluated semi-quantitatively (grading the degree of immunostaining on a scale of
      0-4). To determine if degradation of the extracellular matrix affects lysozyme
      binding, hyaluronidase-treated normal lung tissues were incubated with egg white
      lysozyme, immunostained with the lysozyme antibody, which crossreacts with egg
      white lysozyme, and evaluated for degree of staining. RESULTS: Lysozyme
      immunostaining was significantly increased in lungs with pulmonary emphysema
      compared with normal or fibrotic tissues (3.4 versus 1.6 and 1.9, respectively; p
      < 0.05) and was preferentially associated with interstitial elastic fibres.
      Hyaluronidase-treated lung tissues incubated with lysozyme showed increased
      immunostaining for this protein compared with untreated controls (1.9 versus 1.2;
      p < 0.05). CONCLUSIONS: The results suggest that damage to elastic fibres and/or
      the surrounding extracellular matrix increases lysozyme binding. It is
      hypothesised that attachment of lysozyme to elastic fibres may interfere with
      their repair and possibly enhance the progression of pulmonary emphysema.

PMID- 9659356
TI  - Gene therapy for cystic fibrosis: which postman, which box?
AB  - Since 1989 when the gene responsible for cystic fibrosis was cloned and
      designated the cystic fibrosis transmembrane conductance regulator (CFTR) gene,
      considerable progress has been made in the development of gene therapy for this
      disease. Clinical trials have already been performed using cationic liposome and
      adenoviral based gene transfer systems, measuring the safety and efficacy of this
      new form of treatment, with variable results to date. These two approaches and
      the current progress in airway gene delivery are discussed.

PMID- 9659357
TI  - New ideas on the pathophysiology and treatment of lung disease.
AB  - There is a continuing need for development of new treatments for lung disease.
      Basic scientific investigations are identifying novel targets for the development
      of new approaches to therapy of a range of respiratory conditions. Coupled with
      the advances in technology being harnessed by the pharmaceutical and
      biotechnological industries, there is now an impressive range of potential
      treatments including gene therapy, not just for cystic fibrosis but also for a
      range of inflammatory lung conditions, anti-cytokine and anti-adhesion molecule
      approaches, and targeting of intracellular signal transduction pathways including
      cyclic AMP metabolism, tyrosine kinases and MAP kinases. "Old" molecules such as
      heparin and secretory leukoprotease inhibitor (SLPI) are demonstrating new
      beneficial activities. Simple molecules such as nitric oxide (NO) gas may be
      involved in the pathophysiology of different airway conditions. It is an exciting
      time for respiratory science and a time for optimism for those seeking new
      approaches to the treatment of lung diseases.

PMID- 9659358
TI  - Health effects of passive smoking. 6. Parental smoking and childhood asthma:
      longitudinal and case-control studies.
AB  - BACKGROUND: The relation of parental smoking to wheezing and asthma occurring
      after the first year of life was assessed by a systematic quantitative review of
      case-control and longitudinal studies, complementing earlier reviews of cross
      sectional surveys and wheezing in early childhood. METHODS: Fifty one relevant
      publications were identified after consideration of 1593 abstracts selected by
      electronic search of the Embase and Medline databases using keywords relevant to
      passive smoking in children. The search was completed in April 1997 and
      identified six studies of asthma incidence, seven of prognosis, 22 case-control
      studies, and 10 case series addressing disease severity. RESULTS: Maternal
      smoking was associated with an increased incidence of wheezing illness up to age
      6 (pooled odds ratio 1.31, 95% CI 1.22 to 1.41), but less strongly thereafter
      (1.13, 95% CI 1.04 to 1.22). The long term prognosis of early wheezing illness
      was better if the mother smoked. The pooled odds ratio for asthma prevalence from
      14 case-control studies was 1.37 (95% CI 1.15 to 1.64) if either parent smoked.
      Four studies suggest that parental smoking is more strongly associated with
      wheezing among non-atopic children. Indicators of disease severity including
      symptom scores, attack frequency, medication use, hospital attendance, and life
      threatening bronchospasm were in general positively related to household smoke
      exposure. CONCLUSIONS: The excess incidence of wheezing in smoking households
      appears to be largely non-atopic "wheezy bronchitis" with a relatively benign
      prognosis, but among children with established asthma, parental smoking is
      associated with more severe disease. This apparent paradox may be reconciled if
      environmental tobacco smoke is considered a co-factor provoking wheezing attacks,
      rather than a cause of the underlying asthmatic tendency.

PMID- 9659359
TI  - Lung infections. 3. Pseudomonas aeruginosa and other related species.

PMID- 9659361
TI  - Non-Hodgkin's lymphoma arising in cryptogenic fibrosing alveolitis.

PMID- 9659360
TI  - Pulmonary vasculitis.

PMID- 9659362
TI  - A vibrating trachea.
AB  - A case of relapsing polychondritis presenting as tracheomalacia is reported in
      which an unusual low pitched sound was heard at the mouth and over the chest wall
      during expiration. The sound was associated with expiratory airflow limitation
      and oscillation on the flow trace of approximately 50 Hz. Spectral analysis of
      the sound showed it to have the characteristics of sounds produced by flutter in
      flow limited flexible tubes. These observations suggest that the sound was
      produced by airflow induced flutter in the trachea and main airways and is
      further evidence in support of the dynamic flutter theory of wheeze production.

PMID- 9659363
TI  - Upper airways sarcoidosis presenting as obstructive sleep apnoea.
AB  - Sarcoidosis may present in a number of different ways, affecting many organ
      systems. The case history is presented of a 32 year old woman who presented with
      symptoms of severe obstructive sleep apnoea (OSA) due to infiltration of the
      upper airway by sarcoidosis. To our knowledge this presentation of sarcoidosis
      has not previously been described.

PMID- 9659364
TI  - Why are there so few papers on elderly patients in Thorax?

PMID- 9659365
TI  - Passive smoking in children with asthma.

PMID- 9659366
TI  - Metabolic activation of dopamine o-quinones to o-semiquinones by NADPH cytochrome
      P450 reductase may play an important role in oxidative stress and apoptotic
      effects.
AB  - In this study, it is shown that considerable evidence for the possible pathway by
      which dopamine o-quinone, o-quinone and aminochrome can be activated
      metabolically by NADPH cytochrome P450 reductase to high reactive semiquinones.
      These findings were discussed from a mechanistic standpoint as well as in terms
      of potential physiological implications of dopamine o-quinones and o
      semiquinones' concerted action in oxidative stress and apoptotic events.

PMID- 9659367
TI  - Interaction of peanut root lectin (PRA II) with rhizobial lipopolysaccharides.
AB  - Sugar specific binding of peanut root lectin (PRA II) to peanut specific
      bradyrhizobial lipopolysaccharides (LPS) was demonstrated by gel retardation
      assay and lectin based ELISA. Sephadex G-50 gel purified high molecular weight
      polysaccharides from NC 92 LPS bind PRA II most efficiently. Binding of NC 92 LPS
      only to PRA II and not to PNA, SBA and PSL by Western blot analysis suggests that
      this lectin-LPS interaction is tissue as well as species specific.

PMID- 9659368
TI  - Cytochromes P450 in liver of the turtle Chrysemys picta picta and the induction
      and partial purification of CYP1A-like proteins.
AB  - Cytochromes P450 (CYP) in hepatic microsomes from the turtle Chrysemys picta
      picta and their response to inducers were examined. Freshly caught turtles had
      one protein (59 kDa) detected in western blot with monoclonal antibody 1-12-3 to
      scup CYP1A. That same band and a second band were detected with polyclonal anti
      mouse Cyp1a1. Polyclonal anti-scup P450B (putative CYP2B) recognized three bands
      and anti-scup P450A (putative CYP3A), one band. TCB (3,3',4,4'
      tetrachlorobiphenyl) at 5 mg kg-1 injected once induced EROD activity 3-fold.
      Repeated high-dose injections of TCB, 2,3,3',4,4'-pentachlorobiphenyl, Aroclor
      1254 or beta-naphthoflavone induced CYP1A 20-fold and P450B-related proteins 2-3
      fold. Rates of ethoxy- (EROD) methoxy- (MROD) and pentoxyresorufin O-dealkylases
      and benzo[a]pyrene (B[a]P) hydroxylase (AHH) were induced by these treatments,
      and were correlated with putative CYP1A content. Phenobarbital slightly elevated
      only MROD activity. Ethoxycoumarin (EC) O-deethylase rates were high, 1.6-2.2
      nmol min-1 mg-1 in control and treated turtles, suggesting that EC is not a
      turtle CYP1A substrate. Highly induced EROD rates were 0.06 nmol min-1 mg-1,
      while AHH rates exceeded 4 nmol min-1 mg-1, suggesting that C. picta picta CYP1A
      may prefer PAH substrates. Induction of AHH was reflected in the formation of
      metabolites 3-OH-, 9-OH- and 7-OH-BP and BP-7,8-dihydrodiol (DHD). BP-4,5-DHD was
      not detected. Chromatographic procedures resolved the 59 kDa putative CYP1A from
      the second protein recognized by anti-Cyp1a1. The 59-kDa protein was also
      specifically and highly immunopurified by Mab 1-12-3. Thus, several CYP including
      two CYP1A-related proteins are expressed in turtle liver. Multiple CYP1A genes in
      reptiles may provide an insight into the origin of divergence in the CYP1A
      subfamily. Induction of a CYP1A may be a useful indicator of exposure to Ah
      receptor agonists in turtles.

PMID- 9659369
TI  - Enzymatic properties of endo-beta-N-acetylglucosaminidases from developing tomato
      fruits and soybean seeds: substrate specificity of plant origin endoglycosidase.
AB  - Substrate specificity and some other enzymatic properties of partial purified
      endo-beta-N-acetylglucosaminidases (endo-beta-GlcNAc-ase) from developing soybean
      seeds (Glycine max, Endo-GM) and developing tomato fruits (Lycopersicum
      esculentum, Endo-LE) were studied. The substrate specificity of these two
      endoglycosidases was explored and compared with regard to various pyridylaminated
      N-glycans derived from some naturally occurring glycoproteins. For Endo-GM and
      Endo-LE, several high mannose-type sugar chains bearing alpha 1-2 mannosyl
      residue(s), Man9-6GlcNAc2-PA (PA is pyridylamino) (80-100% relative hydrolysis),
      were most favored substrates followed by Man5GlcNAc2-PA (32% for Endo-LE, 43% for
      Endo-GM), a typical hybrid-type structure (GlcNAc1Man5GlcNAc2-PA; 34% for Endo
      LE, 37% for Endo-GM), and then the common core pentasaccharide of N-glycan
      (Man3GlcNAc2-PA; 9% for Endo-GM and 16% for Endo-LE). On the contrary, both Endo
      GM and Endo-LE could barely hydrolyze the xylose-containing N-glycans
      (Man3Xyl1GlcNAc2-PA, Man3Fuc1Xyl1GlcNAc2-PA) found ubiquitously in plant cells.
      The molecular mass of these two endoglycosidases was approximately 62 kDa by gel
      filtration and both Endo-GM and Endo-LE showed maximal activities for Man6GlcNAc2
      PA in a weak acidic region (pH 6.0-6.5).

PMID- 9659370
TI  - The effects of pH and ionic strength on intrafibrillar hydration in articular
      cartilage.
AB  - The hydration of articular cartilage is an essential determinant of its load
      bearing capacity. Here we have examined the dependence of the amount of
      intrafibrillar water, associated with the collagen molecules in both native and
      PG-depleted cartilage specimens, on the pH and ionic strength of the bathing
      solution, in the presence and absence of an externally applied pressure. We found
      that high ionic strength reduces the collagen intermolecular spacing over a large
      pH range: this is consistent with the electrostatic nature of the interactions
      between the charged groups within the intrafibrillar space. We also found that as
      the pH is lowered from neutral to approximately 3, there is, as expected, a
      gradual increase in the overall positive charge of the intrafibrillar
      compartment. However, surprisingly, this is not accompanied by an increase in the
      intrafibrillar hydration; only at pH 1.8 does the amount of intrafibrillar water
      increase markedly. We suggest that, rather than overall intrafibrillar charge, it
      is specific local axial and azimuthal relationships among collagen molecules in
      the fibril, and more particularly, among their charged amino acid residues, that
      determine the intermolecular collagen spacing, and hence intrafibrillar
      hydration.

PMID- 9659371
TI  - Characterization of pICln phosphorylation state and a pICln-associated protein
      kinase.
AB  - pICln is a ubiquitous cellular protein that has been proposed to be a volume
      sensitive Cl- channel or a channel regulator. Detailed biochemical, cellular and
      molecular characterization of pICln is required to understand its function. Our
      goal in the present investigation was to define further the biochemical
      properties of pICln and the proteins that associate with it. Immunoprecipitation
      of pICln from 32P-orthophosphoric acid-labeled C6 glioma cells revealed that the
      protein is phosphorylated constitutively, primarily on serine residues. Protein
      kinase activity was detected in pICln immunoprecipitates, revealing that a
      constitutively active protein kinase co-precipitates with pICln. A specific
      association between pICln and a protein kinase was also observed in affinity
      assays using a recombinant GST-pICln fusion protein. The pICln-associated kinase
      displayed broad substrate specificity and was inhibited in a concentration
      dependent manner by heparin, zinc and 5,6-dichloro-1-beta-D-ribofuranosylbenose
      (DRB). These characteristics resembled those of casein kinase I and II. The pICln
      associated kinase was not recognized, however, by antibodies against these two
      enzymes. Association of the kinase with pICln was disrupted by increasing
      concentrations of NaCl in the washing buffer, suggesting that electrostatic
      interactions are involved in kinase binding. Mutagenesis experiments corroborated
      this observation. Truncation of pICln demonstrated that two highly charged
      clusters of acidic amino acid residues are both necessary and sufficient for
      kinase binding. Phosphopeptide mapping demonstrated that pICln contains at least
      two phosphorylated serine residues that are located on trypsin cleavage fragments
      rich in acidic amino acid residues. We propose that the kinase or a kinase
      binding protein binds to acidic amino acids located between D101 and Y156 and
      phosphorylates nearby serine residues.

PMID- 9659372
TI  - Effects of Cryptococcus humicola killer toxin upon Cryptococcus terreus envelope:
      combined fluorometric and microscopic studies.
AB  - Killer toxin (microcin) produced by Cryptococcus humicola 9-6 induced interaction
      of the fluorogenic dyes, ethidium bromide, propidium iodide, and hemimagnesium 8
      anilino-1-naphtalenesulfonate, with the sensitive strain of Cryptococcus terreus
      VKM Y-2253. The toxin also made the cells susceptible to cetyltrimethylammonium
      bromide and leaky for K+. When excited at 360 nm, cell-bound ethidium (propidium)
      fluorescence was enhanced by 8-anilino-1-naphtalensulfonate, and cell-bound 8
      anilino-1-naphtalensulfonate fluorescence was quenched by ethidium (propidium),
      indicating energy transfer from 8-anilino-1-naphtalensulfonate to ethidium
      (propidium). These results suggest that at least a portion of the probe molecules
      had the same binding site, possibly the cytoplasmic membrane. The parameters of
      kinetics of microcin action were evaluated fluorometrically. They were found to
      be identical for all probes and depended on microcin concentration. The
      fluorescence increment of ethidium and 8-anilino-1-naphtalensulfonate upon
      binding to microcin-treated cells correlated with the fraction of stainable cells
      and viability.

PMID- 9659373
TI  - Small-angle neutron scattering and dynamic light scattering studies of N- and C
      terminal fragments of ovotransferrin.
AB  - In order to rationalize the physicochemical heterogeneities between the N- and C
      lobes of ovotransferrin (OTf), we have analyzed the structural characteristics of
      the isolated fragments corresponding to the N- and C-terminal halves of OTf
      (OTf/2N and OTf/2C) with and without iron by means of small-angle neutron
      scattering (SANS) using the contrast variation method with solvents of various
      D2O/H2O mixtures, and dynamic light scattering (DLS) measurements. The analyses
      of the internal structural characteristics from SANS data revealed that the
      radius of gyration (Rg) for both fragments decreased to the same extent with iron
      binding, and the structural distortion of OTf/2C was smaller than that of OTf/2N,
      decreasing with iron uptake. The DLS studies showed that the change in the
      diffusion coefficient induced by iron binding to OTf/2C was greater than that to
      OTf/2N. It was inferred that the OTf/2C molecule tends to become more compact on
      the whole by iron binding as compared to the OTf/2N molecule.

PMID- 9659374
TI  - Effect of carotenoids on the respiratory burst of rat peritoneal macrophages.
AB  - The effect of four carotenoids (beta-carotene, lutein, bixin and canthaxanthin)
      on the respiratory burst of rat peritoneal macrophages was investigated. The
      results obtained showed that carotenoids suppressed the luminol-dependent
      chemiluminescence generated from PMA-stimulated macrophages at the beginning and
      after 2 min of the stimulation. Canthaxanthin and bixin had higher suppressive
      activity than beta-carotene and lutein. The changes in absorption spectra of
      carotenoids showed that the absorption by carotenoids was diminished during the
      stimulation of macrophages by PMA and their absorption peaks were either further
      diminished or blue-shifted after addition of L-arginine to the system, indicating
      that the carotenoids were consumed and converted to new compounds during the two
      processes. By using cell-free systems, it was found that carotenoids could
      scavenge superoxide anion generated by xanthine/xanthine oxidase system. Their
      ability to scavenge superoxide anion decreased in the order of canthaxanthin >
      bixin > lutein > beta-carotene. Canthaxanthin also showed the scavenging effect
      on superoxide anion generated from irradiation of riboflavin. The hydroxyl
      radical scavenging activity of carotenoids was investigated in the reaction
      system of Fe2+ and H2O2. There was little difference among their activities. The
      reaction between carotenoids and nitric oxide led to the decreasing absorption
      between 400 and 540 nm and the concomitant appearance of the new absorption peaks
      between 330 and 395 nm. Bleaching of beta-carotene, bixin and canthaxanthin by
      peroxynitrite resulted in the increasing absorption between 290 and 365 nm and
      the diminishing absorption between 400 and 500 nm. But the increasing absorption
      between 280 and 490 nm was observed in bleaching of lutein by peroxynitrite.
      Carotenoids inhibited thiobarbituric acid-reactive substance (TBARS) formation in
      AAPH-induced lipid peroxidation of PC liposomes in air. The results suggest that
      the suppressive effect of carotenoids on the respiratory burst of macrophages may
      be just a way by which carotenoids in vivo protect host cells and tissues from
      harmful effects of oxygen metabolites overproduced by macrophages and enhance the
      generation of specific immune responses.

PMID- 9659375
TI  - In vivo manipulation of L1210 cell cycle phase distribution with alpha
      difluoromethylornithine, 4-amidinoindan-1-one 2'-amidinohydrazone and N1
      acetylspermine.
AB  - We investigated whether the in vivo growth inhibitory effect of the combination
      of 4-amidinoindan-1-one 2'-amidinohydrazone (CGP 48664A) and alpha
      difluoromethylornithine (DFMO) is reversible by treatment with N1-acetylspermine
      (N1-acSp). DBA-2 mice were inoculated with 10(5) L1210 cell i.p. on day 0. From
      day 1 they received 2.50 mg CGP 48664A/kg i.p. once daily and 500 mg DFMO/kg i.p.
      twice daily. On day 5 they received 3 x 2500 nmol N1-acSp i.p. with 15-min
      intervals. L1210 cell numbers, S-phase percentage and polyamine contents, and
      liver and spleen polyamine contents were monitored in the following 48 h. Four
      days treatment with CGP 48664A/DFMO reduced L1210 cell numbers, S-phase, and
      spermidine. N1-acSp treatment increased L1210 spermidine from < or = 8 h and
      percentage S-phase from 12 h. Maxima for spermidine and S-phase were reached at <
      or = 8 and 18 h, respectively. These were below levels of untreated controls.
      Decreases were noted from 12 and 18 h, respectively. N1-acSp was detectable in
      L1210 from 0-18 h. Liver spermidine was decreased by CGP 48664A/DFMO. After N1
      acSp treatment, liver N1-acSp and N1-acSd increased from < or = 8 h, reached
      maxima at < or = 8 and 10 h, respectively, and were undetectable from 15 h. We
      conclude that the in vivo growth inhibitory effect of CGP 48664A/DFMO is
      reversible by N1-acSp treatment. The liver is probably involved in N1-acSp
      terminal catabolism. The effect of the polyamine depletion-repletion scheme on S
      phase cell numbers may be much more profound than present estimates from 5-bromo
      2'-deoxyuridine incorporation.

PMID- 9659376
TI  - In vitro manipulation of L1210 cell cycle kinetics with 4-amidinoindan-1-one 2'
      amidinohydrazone, alpha-difluoromethylornithine and N1-acetylspermine.
AB  - We investigated whether in vitro L1210 growth inhibition by alpha
      difluoromethylornithine (DFMO; 740 microM) and 4-amidinoindan-1-one 2'
      amidinohydrazone (CGP 48664A; 1.7 microM) is reversible with N1-acetylspermine
      (N1-acSp). Influences of N1-acSp dose (1-100 microM), time (0-12 h at 100
      microM), aminoguanidine (AG, 1 mM) and cell numbers (at 1 microM N1-acSp) on
      percentage S-phase, polyamine contents and viability were determined. DFMO/CGP
      48664A decreased percentage S-phase from 58 to 26%, decreased spermidine (Sd) and
      spermine (Sp) contents 3-fold, but did not affect viability. With increasing N1
      acSp dose, S-phase percentage and Sd contents increased concomitantly, reaching
      plateau values that were comparable with those of untreated controls. S-phase and
      Sd content increased from 4-6 h after N1-acSp administration, reaching plateau
      values from 11 and 6 h, respectively. N1-acSp content was dose dependent and
      increased linearly to reach plateau values from 8 h. AG did not affect any of
      these parameters. Addition of 1 microM N1-acSp to decreasing numbers of DFMO/CGP
      48664A-treated cells caused increasing S-phase percentage, Sd and N1-acSp
      contents. We conclude that cell cycle kinetics of cultured L1210 cells can be
      manipulated by the induction of growth inhibition with DFMO/CGP 48664A and its
      subsequent abolishment with N1-acSp. N1-acSp accumulation rate and its subsequent
      conversion to Sd is relatively slow compared with intracellular Sd needs. The
      data support the notion that Sd is the most important polyamine for growth.

PMID- 9659377
TI  - Taxol-DNA interactions: fluorescence and CD studies of DNA groove binding
      properties of taxol.
AB  - Taxol is perhaps the most successful drug used for the treatment of various
      cancers. Comprehensive literature accumulated on therapeutics of the drug has
      indicated numerous side effects. In this paper, by use of fluorescence
      spectroscopy, it is shown that taxol binds to DNA with an affinity constant (Ka)
      of 1.08 x 10(7) M-1. This binding is accompanied by a large 'red edge excitation
      shift' (REES) of fluorescence emission maximum in taxol-DNA complex. The results
      point to an interaction of taxol with its core eight-membered ring in the DNA
      groove and the three phenyl rings projecting away from the DNA. The drug
      encompasses about two base pairs of DNA upon binding to it. Systematic studies
      with taxol analogues confirms such a mode of binding. These interesting findings
      on hitherto unknown taxol-DNA interactions may have clinical implications in view
      of its large number of side effects and pharmacokinetics.

PMID- 9659378
TI  - Induction of nuclear respiratory factor-1 expression by an acute bout of exercise
      in rat muscle.
AB  - Nuclear respiratory factor 1 (NRF-1) is a regulatory factor of nuclear genes for
      respiratory subunits and for components of the mitochondrial transcription and
      replication machinery. This study investigated the effects of an acute bout of
      aerobic exercise on the postexercise expression of mRNA for NRF-1 and RNA moiety
      of endonuclease for mitochondrial RNA processing (MRP-RNA) in soleus muscle of 5
      days-trained and untrained rats. In the trained group, rats were run on a motor
      driven treadmill at a speed of 25 m/min for 90 min/day for 5 days. On the final
      day, rats were run by the same procedures and were sacrificed at various
      postexercise time points (0.5, 3, 6, and 24 h). The basal level of cytochrome
      oxidase activity was increased by the training, which was associated with the
      increase in the expression of mRNAs for subunit VIc and III of the enzyme. The
      NRF-1 mRNA expression was transiently increased by approximately 35% at the time
      point of 6 h after exercise, although the basal level of the expression was not
      altered by training. A similar transient increase (approximately 50%) in NRF-1
      expression by the acute bout of exercise was also observed in untrained rats. In
      contrast to the NRF-1 expression, the basal level of MRP-RNA abundance was not
      altered by 5 days training and was not affected by the single exercise bout in
      either 5 days-trained or untrained rats. These results suggest that the
      postexercise increase in NRF-1 mRNA expression in rat skeletal muscle may be an
      early response to endurance exercise for an enhancement of the mitochondrial
      oxidative capacity.

PMID- 9659379
TI  - Murine betaglycan primary structure, expression and glycosaminoglycan attachment
      sites.
AB  - The primary structure of murine betaglycan, also known as transforming growth
      factor beta (TGF-beta) type III receptor, was deduced from the nucleotide
      sequence of a cDNA clone isolated from a heart library. Murine betaglycan is a
      single spanning membrane polypeptide of 850 amino acids which is highly similar
      to betaglycan of other species. Transfection of this cDNA into COS1 cells
      resulted in the expression of a membrane proteoglycan that binds TGF-beta and is
      recognized by antibodies raised against rat betaglycan. COS1 cells transfected
      with the double mutant Ser533Ala; Ser544Ala of the murine betaglycan cDNA
      produced a TGF-beta type III receptor devoid of glycosaminoglycan chains.

PMID- 9659380
TI  - Identification of the Rhizobium meliloti alcohol dehydrogenase gene (adhA) and
      heterologous expression in Alcaligenes eutrophus.
AB  - A screen for Rhizobium meliloti genes which improve the growth of Alcaligenes
      eutrophus on sucrose identified the first alcohol dehydrogenase gene (adhA)
      isolated from the Rhizobiaceae. R. meliloti adhA is constitutively expressed in
      A. eutrophus and has alcohol dehydrogenase activity. R. meliloti adhA mutants
      retain some alcohol dehydrogenase activity.

PMID- 9659381
TI  - Amino acid sequence of a myotoxic Lys49-phospholipase A2 homologue from the venom
      of Cerrophidion (Bothrops) godmani.
AB  - The complete amino acid sequence of myotoxin II (godMT-II), a myotoxic
      phospholipase A2 (PLA2) homologue from the venom of the Central American
      crotaline snake Cerrophidion (Bothrops) godmani, was determined by direct protein
      sequencing methods. GodMT-II is a class II PLA2 showing a Lys instead of Asp at
      position 49. An additional substitution in the calcium binding loop region (Asn
      instead of Tyr at position 28) suggests the lack of enzymatic activity observed
      in this toxin is due to loss of its ability to bind the co-factor Ca2+, since the
      residues involved in forming the catalytic network of PLA2s (His-48, Tyr-52 and
      Asp-99) are conserved in godMT-II. This myotoxin shows highest sequence homology
      with other Lys-49 PLA2 s from Bothrops, Agkistrodon and Trimeresurus species,
      suggesting that they constitute a conserved family of proteins, yet in contrast
      presents lower homology with Bothrops asper myotoxin III, a catalytically-active
      PLA2. The C-terminal region of godMT-II, which is rich in cationic and
      hydrophobic residues, shares high sequence homology to the corresponding region
      in the myotoxin II from B. asper, which has been proposed to play an important
      role in the Ca(2+)-independent membrane damaging activity.

PMID- 9659382
TI  - E. coli HPII catalase interaction with high spin ligands: formate and fluoride as
      active site probes.
AB  - E. coli catalase (HPII) wild type and mutant enzymes (heme dcis-containing) were
      examined (i) to study the role of a distal haem cavity residue, asparagine-201,
      in high spin ligand binding and (ii) to compare the differences in this binding
      between heme d and protoheme enzymes such as that from beef liver (BLC). High
      spin fluoride complexes were formed by all three HPII catalases examined, wild
      type (201 asn) and 201gln and 201asp mutants, but with a lower fluoride affinity
      than that of BLC. The binding of fluoride was pH-dependent, indicating that a
      proton is bound as well as a fluoride anion. HPII 201glu and 201 asp mutants
      showed lower affinities for fluoride than did wild type, unlike their reactions
      with cyanide which are essentially independent of the nature of residue 201. The
      equilibria and rates of fluoride and formate binding to BLC were reexamined. The
      rates of reaction with formate were similar to those reported previously.
      Dissociation rates for fluoride-catalase are higher than for formate suggesting
      that the latter may be bound differently. High spin complexes between formate and
      all three HPII forms showed a substantially higher affinity than that of BLC for
      HPII wild type and progressively lower affinities for the two mutants. As with
      fluoride the reactions were pH-dependent, indicating that a proton is bound
      together with the formate anion (or that undissociated formic acid is the
      ligand). The known structures of the heme groups and heme pockets involved are
      discussed. Formate may be bound by secondary H-bounds within the heme pocket in
      both heme dcis and protoheme enzymes. The nature of the heme pocket and the heme
      access channel may be more important than the chemical nature of the prosthetic
      group in controlling both high spin ligand interactions and reactions with the
      substrate hydrogen peroxide.

PMID- 9659383
TI  - A unified model of c-erbB receptor homo- and heterodimerisation.
AB  - The c-erbB receptor tyrosine kinase family plays an important role in cell
      regulation. Receptor activation proceeds by the formation of receptor homo-
      and/or hetero-dimers and is promoted by the binding of a cognate ligand at the
      cell surface. While some experimental work has demonstrated that the formation of
      heterodimers can influence a cellular response, the extent of heterodimerisation
      has not been accurately assessed: the assortment of receptors and ligands gives
      rise to a complex combinatorial system for which intuitive prediction of homo-
      and hetero-dimerisation is difficult. We present a mathematical model which
      combines observations for homo-dimerisation with the additional interactions
      arising from the presence of multiple c-erbB receptors. We provide a simple
      explanation for the apparently conflicting results for binding studies carried
      out with either solubilised receptors, vesicles or cells and our model predicts
      binding behaviour which is compatible with published experimental findings for
      cells expressing either one or two c-erbB receptors. This model establishes the
      basis for interpretation of ligand binding experiments, where variations in the
      apparent ligand affinity can be attributed to changes in receptor expression or
      ligand preferences according to the binding profile.

PMID- 9659384
TI  - Purification and characterisation of a tripeptidyl aminopeptidase I from rat
      spleen.
AB  - A tripeptidyl aminopeptidase I with an M(r) of 47,000 Da has been purified from
      rat spleen. The N-terminal sequence of the enzyme and internal sequences did not
      resemble that of any known protein. The enzyme cleaves tripeptides from synthetic
      substrates provided that the N-terminus is unsubstituted and the amino acid in
      the P1 position is not charged. The enzyme also cleaves small peptides
      (angiotensin II and glucagon) releasing tripeptides but does not appear to
      demonstrate any preference for amino acids on either side of the cleavage site.
      The enzyme had maximum activity at pH 4 but was unstable above pH 7. Rat spleen
      tripeptidyl peptidase I was not inhibited by classical inhibitors of serine,
      cysteine, aspartate or metalloproteinases. The peptidase was potently inhibited
      by a series of substrate-based tripeptidyl chloromethyl ketones (Ki's of 10(-6)
      10(-8) M). Inhibition was rapid and reversible. This mode of inhibition is
      different to the interaction between chloromethyl ketones and cysteine or serine
      peptidases. These tripeptidyl chloromethyl ketones were also inhibitors of bone
      resorption using an in vitro assay suggesting that a tripeptidyl peptidase is
      involved in the degradation of bone matrix proteins.

PMID- 9659385
TI  - Mapping of functional sites on the primary structure of the tail lysozyme of
      bacteriophage T4 by mutational analysis.
AB  - Tail lysozyme of bacteriophage T4, product of gene 5 (gp5), functions upon
      infection by locally digging a hole in the peptidoglycan layer, so that the tail
      tube, through which the phage DNA is injected, can penetrate to the inner
      membrane. It has been inferred from DNA sequence and expression of the tail
      lysozyme on a plasmid in Escherichia coli that the tail lysozyme is synthesized
      as a precursor of 62 K and is later cleaved to form a mature tail lysozyme of 42
      K. Furthermore, gp5 has a region that is highly homologous to T4 lysozyme, gpe,
      that is the product of gene e and functions for 'lysis from within'. As an
      approach to elucidation of structure-function relationship of gp5, we determined
      mutational sites of gene 5 mutants that have heat sensitive virions, are
      temperature sensitive for growth, or require an amber suppressor. All the
      mutational sites were mapped in the region corresponding to the mature tail
      lysozyme. Among the ts mutants, 5ts1 was a pseudo-revertant of an amber mutant
      which bypasses gene e. It was mapped in the region which had a high homology to
      gpe, which is well known as T4 lysozyme. The other mutational sites will be also
      discussed in relation to the phenotypes of the mutants.

PMID- 9659386
TI  - Spectroscopic manifestations of flavomononucleotide dimers in polyvinyl alcohol
      films.
AB  - Absorption and fluorescence spectra of flavomononucleotide (FMN) in polyvinyl
      alcohol films (PVA) over a very wide concentration range are investigated. The
      dimerization constant as well as the pure monomer and dimer spectra are
      calculated and the structural parameters of FMN dimer are established. Excitation
      wavelength and temperature dependencies of FMN/PVA fluorescence spectra for
      different FMN concentrations were carried out. These measurements together with
      those of absorption reveal that dimers are imperfect traps for excitation energy
      and that the energy transfer can occur both in forward and in reverse direction.
      Moreover, it was shown that the observed temperature changes in fluorescence
      spectra may be qualitatively explained by the effect of inhomogeneous broadening
      of FMN energy levels and by the presence of fluorescent dimers.

PMID- 9659387
TI  - Effect of 3-hydroxyanthranilic acid on mushroom tyrosinase activity.
AB  - Tyrosinase is a copper containing protein which catalyzes the hydroxylation of
      monophenols and the oxidation of diphenols to o-quinones. The monophenolase
      activity of tyrosinase is characterized by a typical lag time. In this paper the
      influence of 3-hydroxyanthranilic acid on monophenolase activity of tyrosinase is
      reported. 3-Hydroxyanthranilic acid reduced the lag time of tyrosinase when the
      enzyme acted on N-acetyl-L-tyrosine and on 4-tert-butylphenol. In the presence of
      3-hydroxyanthranilic acid, the reaction product 4-tert-butyl-o-benzoquinone,
      derived from 4-tert-butylphenol oxidation, was formed at a higher rate than in
      its absence. The results reported in this paper indicate that 3
      hydroxyanthranilic acid could affect the enzymic activity of mushroom tyrosinase
      probably by acting as a diphenol substrate. A K(m) value of 0.78 mM was
      calculated for 3-hydroxyanthranilic acid as substrate. When tyrosinase acted on 4
      tert-butylphenol, K(m) for 3-hydroxyanthranilic acid as a cofactor was estimated
      to be 37.5 microM. No effect was observed on the diphenolase activity of the
      enzyme acting on 4-tert-butylcatechol in the presence of 3-hydroxyanthranilic
      acid.

PMID- 9659388
TI  - Uncompetitive inhibition by adenine of the RNA-N-glycosidase activity of ribosome
      inactivating proteins.
AB  - Ricin is a member of the ribosome-inactivating protein (RIP) family with RNA-N
      glycosidase activity which inactivates eukaryotic ribosomes by specifically
      removing adenine from the first adenosine of a highly conserved GAGA loop present
      in 28S rRNA. Free adenine protects ribosomes in cell-free systems from
      inactivation by ricin. Protection by adenine is highly specific, since AMP,
      adenosine and modified adenines (1-methyladenine and ethenoadenine) were
      completely ineffective. Kinetic analysis of the behaviour of adenine as inhibitor
      of the RNA-N-glycosidase reaction catalysed by ricin, Shiga-like toxin I and
      momordin, two other members of the RIP family, established that inhibition was of
      the uncompetitive type, the inhibitor binding to the enzyme-substrate complex.
      Adenine did not protect ribosomes from alpha-sarcin, an RNAase that inactivates
      ribosomes by cleaving the phosphodiester bond located in the GAGA loop at one
      nucleotide distance from the adenosine depurinated by the RNA-N-glycosidases.
      Adenine at the concentration of 1 mM lowered 1.5-fold the toxicity of ricin and
      3.7-fold that of Shiga-like toxin I on Vero cells in culture. The same
      concentration of adenine decreased 2.4-fold the inactivation of isolated
      ribosomes by ricin, 2.8-fold the inactivation by Shiga-like toxin I and 20-fold
      that by momordin.

PMID- 9659389
TI  - Kinetic properties of the C-terminal Src kinase, p50csk.
AB  - Csk is an important regulator of tyrosine kinases of the Src family. In this
      paper, we have characterised the kinetics and catalytic properties of a highly
      active and stable enzyme obtained in milligram amounts by expressing the enzyme
      as a fusion protein with glutathione-S-transferase (GST) in Escherichia coli.
      Using the synthetic polyamino acid poly(Glu, Tyr) as substrate,
      phosphotransferase activity was linear for 7-8 min with Mg2+ and 5 min with Mn2+.
      With Mg2+ and Mn2+, respectively, K(m) (ATP) was 56.9 +/- 6.2 and 5.4 +/- 0.6
      microM and Vmax was 293 +/- 52 and 217 +/- 38 pmol phosphate transferred
      (microgram Csk)-1 min-1. Optimal concentrations of Mg2+ and Mn2+ were 4-10 mM and
      2-3 mM, respectively, and higher concentrations of both cations were inhibitory.
      The Csk activity was highly sensitive to monovalent (Na+, K+) and divalent (Ca2+)
      cations, the sensitivity being 2-5-fold higher with Mg2+ than Mn2+. Physiological
      concentrations of Ca2+ (less than 10 microM) were without effect.
      Autophosphorylation of Csk was demonstrated in vitro, but did not influence the
      catalytic activity. Addition of inorganic phosphate above 100 microM strongly
      inhibited Csk catalytic activity towards poly(Glu, Tyr) in the presence of Mn2+,
      but not in the presence of Mg2+. Phosphorylation of a physiological substrate
      (Lck) and autophosphorylation of Csk was not inhibited by phosphate, indicating
      that the phosphate-dependent inhibition of Csk activity was substrate specific.

PMID- 9659390
TI  - Molecular characterization of the human carbonic anhydrase-related protein (HCA
      RP VIII).
AB  - The very evolutionarily conserved human carbonic anhydrase-related polypeptide
      (CA-RP VIII) lacks the carbon-dioxide hydration-activity, characteristic of the
      enzymatically active carbonic anhydrases. We have expressed HCA-RP VIII as a
      glutathione-S-transferase fusion protein (GST-HCA-RP VIII). The purified HCA-RP
      VIII showed a substantially higher apparent molecular weight by gel-filtration
      compared to the molecular weight calculated from the amino acid sequence,
      indicating a larger than expected Stoke's radius. Like other studied CA's, the
      protein unfolds through two transitions at increasing concentrations of guanidine
      hydrochloride. The far-UV CD spectra of HCA-RP VIII indicates a secondary
      structure similar to that of the catalytically active HCA II. The very high
      sequence identity between human and mouse CA-RP VIII (98%), might indicate that
      the function of the protein involves binding of another protein. However, an
      attempt to use the GST-HCA-RP VIII fusion protein to affinity purify a ligand was
      unsuccessful.

PMID- 9659391
TI  - Secondary structure of an antibacterial peptide Abp3 studied by two-dimensional
      proton-NMR.
AB  - An antibacterial peptide Abp3, an analogue of cecropin B, was investigated by two
      dimensional proton-NMR at pH 5.0 in aqueous solution with 15% (v/v)
      hexafluoroisopropanol. The peptide, which consists of 35 amino acids, was
      synthesized chemically. Most resonances of the main-chain and side-chain protons
      were assigned. Several medium range NOE connectivities were observed, showing two
      separate alpha-helices with one amphiphilic in N-terminal domain (residues 5-21)
      and the other hydrophobic in C-terminal domain (residues 25-35) and a hinge
      region between them. The J coupling constants and the chemical shifts in these
      sections also supported the conclusion.

PMID- 9659392
TI  - Solvent perturbation of the allosteric regulation of aspartate transcarbamylase.
AB  - Escherichia coli aspartate transcarbamylase (ATCase) catalyzes the first
      committed step in pyrimidine biosynthesis, the condensation of aspartate and
      carbamyl phosphate. ATCase is positively allosterically regulated by ATP and
      negatively regulated by CTP. We have used mild solvent perturbation to gain
      global molecular information about the mechanism of heterotropic allostery. The
      [NaCl], temperature, and osmotic pressure dependence of the enzymatic activity of
      ATCase has been examined in the presence and absence of allosteric effectors. The
      results indicate that: 1) Regulation of aspartate binding by CTP appears to
      involve a unique set of electrostatic interactions not involved in enzyme
      function in the presence of ATP or in the absence of effectors. 2) Aspartate
      binding is enthalpically driven in the presence and absence of allosteric
      effectors. 3) The apparent enthalpy and entropy of aspartate binding (delta H,
      delta S), and activation energy of catalysis (Ea) are substantially altered in
      the presence of CTP but not ATP. 4) The change in hydration of ATCase upon
      substrate binding is the same in the presence and absence of allosteric
      effectors. 5) The linkage between heterotropic and homotropic allostery is
      different for ATP and CTP.

PMID- 9659393
TI  - Klenow fragment and DNA polymerase alpha-primase fromserva calf thymus in water
      in-oil microemulsions.
AB  - The activity of DNA polymerase alpha-primase complex from calf thymus and Klenow
      fragment of E. coli DNA polymerase 1 has been studied in reverse microemulsions
      formed by sodium bis(2-ethylhexyl) sulfosuccinate (AOT), sodium dodecylsulfate
      (SDS), cetyl trimethyl ammonium bromide (CTAB), polyoxyethylene 20 cetyl ether
      (Brij 58), and Triton X-114 in decane. DNA polymerases were not active in AOT,
      CTAB, and SDS reverse microemulsions, but these enzymes catalyzed DNA synthesis
      in Brij 58 and its mixture with other surfactants. We have also found the system
      composed from the Triton X-114, SDS, CTAB, and Brij 58 (concentration of 128, 25,
      15, and 10 mM, respectively) in hexanol-decane (1:12 v/v), in which DNA
      polymerases revealed maximum activity. The above system was optically
      transparent, fluid, and stable during a few hours with a water-surfactants molar
      ratio up to 160. The pH dependence of DNA polymerase activity was not
      significantly different in comparison with water; however, DNA polymerase was
      sensitive to ionic strength in microemulsions. The dependence of DNA polymerase
      activity on w0 was the curve with a few optima. DNA polymerases synthesized more
      products in water than in reverse microemulsions, and the processivity of Klenow
      fragment decreased. An increase of the water content resulted in an increase of
      DNA polymerase processivity.

PMID- 9659394
TI  - A study of the specificity of barley chymotrypsin inhibitor 2 by cysteine
      engineering of the P1 residue.
AB  - A combination of oligonucleotide-directed mutagenesis and chemical modification
      was used to produce reactive site (P1) variants of chymotrypsin inhibitor II
      (CI2) in an attempt to create more potent inhibitors and examine inhibitory
      specificity. Mutagenesis to introduce a unique cysteine (CI2M59C) followed by
      modification to S-carboxamidocysteine with iodoacetamide produced a 7-fold more
      potent inhibitor of subtilisin BPN' than the wild type inhibitor. Modification
      with iodoacetic acid, which gives a negatively charged P1 residue (S
      carboxymethylcysteine), generates a weaker inhibitor of subtilisin BPN' and
      chymotrypsin. Further chemical modification experiments of CI2M59C with a series
      of iodoalkanes of increasing chain lengths was used to determine the optimal P1
      side chain length required for potent inhibition of porcine pancreatic elastase.
      A trend was observed which implies that for CI2 the original methionine residue
      or its isostere S-ethylcysteine are most effective residues at this position and
      not alanine as might have been expected from the substrate specificity. The
      mutant CI2M59C did not inhibit human neutrophil elastase. The iodoalkane
      modifications not only resulted in recovery of inhibitory activity but also
      proved to be substantially more potent inhibitors of human neutrophil elastase
      than wild-type CI2.

PMID- 9659395
TI  - X-ray studies on cross-linked lysozyme crystals in acetonitrile-water mixture.
AB  - Tetragonal crystals of hen egg white lysozyme were cross-linked and subjected to
      X-ray diffraction study in acetonitrile-water media with different acetonitrile
      concentrations. Crystals in neat acetonitrile did not scatter X-ray well.
      Structures of crystals in neat water, in 90% and 95% acetonitrile, and crystal
      back-soaked from acetonitrile to water, were determined to about 2 A resolution.
      For crystals in both 90% acetonitrile, and crystal back-soaked from acetonitrile
      to water, were determined to about 2 A resolution. For crystals in both 90% and
      95% acetonitrile, only one protein-bond acetonitrile molecule is found in the
      active site cleft, and its location and binding-protein mode is similar to the C
      subunit of polysaccharide. The alteration in conformation and hydrogen-bond
      pattern involving water as solvent causes the reduction of the protein's
      flexibility in organic media. The back-soaked crystal regained its ordinary three
      dimensional structure in water.

PMID- 9659396
TI  - Purification and primary structure analysis of two cytochrome c2 isozymes from
      the purple phototrophic bacterium Rhodospirillum centenum.
AB  - The isolation and amino acid sequences of two cytochromes c-552 from the
      thermotolerant bacterium Rhodospirillum (R.) centenum have been determined. They
      are very similar to one another with 85% identity. They are homologous to the
      cytochromes c2 from purple bacteria with approximately 67% identity to that from
      Rhodopseudomonas (Rps.) palustris compared to only 42% identity with others of
      the c2 subclass. In addition, they share an unusual six-residue insertion with
      Rps. palustris cytochrome c2 not found in any other cytochrome. The relationship
      with Rps. palustris is thus highly significant. The redox potentials of the R.
      centenum isozymes are 293 and 316 mV. Although the proteins have strongly
      different iso-electric points, both have three conserved lysine residues at the
      proposed site of electron transfer. These results suggest that they may be
      functionally interchangeable.

PMID- 9659397
TI  - The LuxR regulator protein controls synthesis of polyhydroxybutyrate in Vibrio
      harveyi.
AB  - The LuxR regulatory protein of Vibrio harveyi has been shown to control synthesis
      of polyhydroxybutyrate (PHB) as well as luminescence so as to occur at high cell
      density, suggesting that it is a general regulatory protein. Mutants defective in
      the production of LuxR (D1, D34, and MR1130) were found to be missing PHB, whose
      synthesis could be restored by complementation with luxR. Triparental mating with
      a V. harveyi genomic library revealed the presence of three genomic clones (G1,
      G2 and G3) that could also restore PHB synthesis and luminescence to cells which
      express low levels of luxR (D1 and D34) but not to luxR- cells (MR1130)
      suggesting that luxR expression was being stimulated. Analyses of luxR mRNA
      levels by mRNA dot blot hybridization and by primer extension confirmed that luxR
      mRNA levels were increased 4 to 7-fold in the D1 and D34 cells by the G1, G2 and
      G3 fragments and show that expression of a single genomic copy of luxR is
      sufficient to restore synthesis of PHB. The results demonstrate that V. harveyi
      LuxR controls the induction of a process not intimately involved in the
      bioluminescence system and clearly distinguishes its role in V. harveyi from that
      of LuxR from Vibrio (Photobacterium) fischeri, which has only been associated
      with regulation of light emission.

PMID- 9659398
TI  - Cold inactivation and dissociation into dimers of Escherichia coli tryptophanase
      and its W330F mutant form.
AB  - The kinetics and mechanism of reversible cold inactivation of the tetrameric
      enzyme tryptophanase have been studied. Cold inactivation is shown to occur
      slowly in the presence of K+ ions and much faster in their absence. The W330F
      mutant tryptophanase undergoes rapid cold inactivation even in the presence of K+
      ions. In all cases the inactivation is accompanied by a decrease of the coenzyme
      420-nm CD and absorption peaks and a shift of the latter peak to shorter
      wavelengths. The spectral changes and the NaBH4 test indicate that cooling of
      tryptophanase leads to breaking of the internal aldimine bond and release of the
      coenzyme. HPLC analysis showed that the ensuing apoenzyme dissociates into
      dimers. The dissociation depends on the nature and concentration of anions in the
      buffer solution. It readily occurs at low protein concentrations in the presence
      of salting-in anions Cl-, NO3- and I-, whereas salting-out anions, especially
      HPO4(2-), hinder the dissociation. K+ ions do not influence the dissociation of
      the apoenzyme, but partially protect holotryptophanase from cold inactivation.
      Thus, the two processes, cold inactivation of tryptophanase and dissociation of
      its apoform into dimers exhibit different dependencies on K+ ions and anions.

PMID- 9659399
TI  - Cloning, expression, and characterization of a novel guanylate-binding protein,
      GBP3 in murine erythroid progenitor cells.
AB  - We report the molecular cloning of a novel guanylate-binding protein (GBP),
      termed mouse GBP3 (mGBP3) in Friend virus-induced mouse erythroid progenitor
      (FVA) cells. The 71-kDa mGBP3 belongs to a family of known GBPs that contain the
      first two consensus motifs, GXXXXGK(S/T) and DXXG, but lack the third element,
      (N/T)KXD, found in typical GTP-binding proteins. Recombinant mGBP3 protein,
      expressed using a baculovirus expression system, binds to agarose-immobilized
      guanine nucleotides (GTP, GDP and GMP). Moreover, mGBP3 has been found to have an
      intrinsic GTPase activity with K(m) and Vmax values of 77 +/- 4 microM and 21 +/-
      0.5 pmol min-1 microgram-1 of protein, respectively. The mGBP3 is distinct from
      the other GBPs, in that it does not have an isoprenylation/methylation motif CAAX
      at the carboxyl terminus. The mGBP3 appears to be localized in the cytosol based
      on immunofluorescence staining. Although the mGBP3 transcript is expressed to a
      varying degree in numerous mouse tissues, the message is most abundant in FVA
      cells. The mGBP3 transcript increases in FVA cells undergoing differentiation to
      a maximum within a few hours and then decreases to an undetectable level by 24 h.
      These results, taken together, suggest that mGBP3 is a novel member of a family
      of guanylate-binding proteins, which plays a role in the erythroid
      differentiation. The nucleotide sequence reported in this paper has been
      submitted to the GenBank with accession number U44731.

PMID- 9659400
TI  - Enzymatic activity and partial purification of solanapyrone synthase: first
      enzyme catalyzing Diels-Alder reaction.
AB  - In cell-free extracts of Alternaria solani, an enzymatic activity converting
      prosolanapyrone II to solanapyrones A and D via oxidation and subsequent Diels
      Alder reaction has been found. Chromatography with DEAE-Sepharose provided two
      active fractions, pools 1 and 2. The former fraction converted prosolanapyrone II
      to solanapyrones A and D in a ratio of 2.2:1 with optical purities of 99% and 45%
      ee, respectively. The latter fraction did so in a ratio of 7.6:1 with 99% and
      nearly 0% ee, respectively. The enzyme partially purified from pool 2 native
      molecular weight of 40-62 kD and a pl of 4.25. The high reactivity of
      prosolanapyrone III in aqueous solution and the chromatographic behavior of the
      enzyme in pool 2 suggest that a single enzyme catalyzes both the oxidation and
      Diels-Alder reaction.

PMID- 9659401
TI  - Motifs involved in interchain binding at the tail-end of spectrin.
AB  - Segments 20-22 of alpha-spectrin and 1-3 of beta-spectrin are required for high
      avidity interchain binding at the tail-end of the molecule. Here, sequence
      analysis guided by the crystal structure of spectrin's repeating segments was
      used to redefine the boundaries of a repetitive beta segment that is critical for
      interchain binding and demonstrate the contribution of non-repetitive spectrin
      segments in high avidity interchain binding. Our results show that several motifs
      together are required for high avidity binding, indicating that interchain
      binding at the tail-end of the spectrin molecule depends on the long distance
      coordination of several different elements. We also explored the role of unusual
      motifs contained in beta segments involved in interchain binding. A row of basic
      residues and a row of small hydrophobic residues were found not to be required
      for interchain binding, suggesting that their conservation among species reflects
      functions unrelated to interchain binding. The octamer between segments beta 2
      and beta 3 that maintains a specific register between true binding sites was
      found to have an indirect role in interchain binding by stabilizing neighboring
      segments. A 5-residue domain in segment beta 2 (EKPPK) was required for
      interchain binding because it sustains normal helix-helix interactions within
      segments beta 2.

PMID- 9659402
TI  - AP30, a differential protein marker for perilymph and cerebrospinal fluid in
      middle ear fluid, has been purified and identified as human apolipoprotein D.
AB  - Using two-dimensional (2-D) gel electrophoresis, human perilymph and
      cerebrospinal fluid have been shown to be highly enriched for an acidic protein
      with MR 30,000, we designated it as AP30. The protein exhibits charge
      heterogeneity, with at least eight isoforms visible between pI 4.5 to 5.5 on 2-D
      gels. Purification of the protein was carried out by ammonium sulfate
      precipitation, polybuffer exchanger column chromatofocusing, and acetone
      fractional precipitation. The resulting preparation also contains eight spots in
      the acidic area of 2-D gels, and one broad band located at Mr 30,000 by SDS-PAGE.
      Digestion of AP30 with neuraminidase causes the isoforms to shift to a more basic
      position and to consolidate into two primary spots, indicating that AP30 is a
      variably sialylated glycoprotein. Amino acid analysis of AP30 revealed an amino
      acid content very similar to that of human apolipoprotein D. Attempts to
      determine the amino acid sequence demonstrated that the N-terminus is blocked.
      Edman sequencing of two peptide fragments, generated by cyanogen bromide cleavage
      of AP30, both revealed sequences having 100% identity to human apolipoprotein D.
      Western blot analysis of AP30 with the antibody against authentic human
      apolipoprotein D demonstrated a high degree of cross-reactivity. These studies
      indicate that AP30 from human perilymph and cerebrospinal fluid is a member of
      the apolipoprotein D family.

PMID- 9659403
TI  - Signal transduction pathways regulating the development of alpha beta T cells.

PMID- 9659404
TI  - Highlights of the 1998 Wnt meeting, Cambridge, MA, January 9-11.

PMID- 9659405
TI  - 1997 Salk Institute/EMBL meeting on Oncogenes and Growth Control, Salk Institute,
      La Jolla, California, 16-20 August 1997.

PMID- 9659406
TI  - Cell signaling in growth and development: the 11th Annual CABM Symposium, October
      8-9, 1997.
AB  - While many topics were discussed during this symposium, several common themes
      emerged from the presentations. First, it is increasingly evident that regulation
      of ligand-receptor interactions is complex and can occur at nearly every
      conceivable step, including protein processing for release from or tethering to
      the cell surface, diffusibility through tissues, binding to soluble inhibitors,
      and competition with antagonists for receptor binding. In particular, the
      availability of these regulatory steps allows for a range of potential mechanisms
      by which ligand signaling can be modulated by other protein factors, such as in
      the case of fringe and its effects on signaling through the Notch receptor.
      Secondly, a major area of effort in the signaling field will increasingly focus
      on how cells integrate the signals received from different pathways to coordinate
      specific developmental responses. For example, as McMahon pointed out, the major
      signaling pathways that govern the anterior-posterior, dorsal-ventral, and
      proximal-distal axes of the developing limb bud have now been identified, yet it
      is completely unclear how these pathways interact to produce positional
      information in three dimensions. Thirdly, biochemical and structural
      investigations are now providing insights into the nature of the feedback
      mechanisms that regulate the strength and duration of activated signals, and how
      in some cases, these feedback loops can also provide a 'memory' of the signaling
      response, such as in the case of the adaptation found in bacterial chemotaxis.
      Finally, the structural analyses of signal transducing molecules remind us of the
      necessity to understand the mechanistic details of how active and inactive states
      are maintained, particularly since distant protein modifications can lead to
      global conformational changes that alter protein activity. These and other
      general insights underscore the value of broad-based meetings that cut across a
      range of disciplines and methodologies, such as this CABM symposium, and provide
      ideas for future directions of investigation.

PMID- 9659407
TI  - A timely look at micronutrients and urbanization in Brazil.

PMID- 9659408
TI  - The I.U.N.S. gains from participation with Brazilian colleagues' deepening
      interest in urban nutrition.

PMID- 9659409
TI  - Environmental factors affecting nutritional status in urban areas of developing
      countries.
AB  - The demographic and economic transition that many developing countries are
      undergoing is producing important changes in diet and lifestyle that greatly
      impact on disease risks. Among the risk behaviors associated with socioeconomic
      transition and urbanization are excessive dietary fat intake, sedentary
      lifestyle, smoking, and environmental contamination. Combined with a reduced
      infant mortality and increased life expectancy, those risk factors lead to an
      increasing prevalence of chronic disease like non-insulin dependent diabetes and
      coronary heart disease. This disease. This disease profile is a relatively new
      phenomenon in developing countries, where health programs have traditionally
      focused on "acute" interventions such as immunization or oral rehydration. A new
      approach will be needed to address chronic diseases, which frequently demand a
      life-long and technically complex medical management, and may have significant
      impact on the quality of life and productivity of the population. Efforts to
      address this situation should focus on a) expanding the information base on diet,
      nutritional status and lifestyle changes in populations migrating to urban areas;
      b) developing and evaluating approaches for improving diet quality in urban
      populations, including fortification and community-based supplementation
      programs; c) understanding better the social and behavioral determinants of
      nutritional status in the urban poor; and d) defining the role of the food
      industry and of agricultural production for improving the quality of the food
      supply in urban areas.

PMID- 9659410
TI  - The role of homocysteine, folate and other B-vitamins in the development of
      atherosclerosis.
AB  - Recently, elevated homocysteine blood concentrations have been identified as an
      independent risk factor for the development of atherosclerotic lesions. The amino
      acid homocysteine is metabolized in the human body involving the vitamins folic
      acid, B12 and B6 as essential cofactors and coenzymes, respectively. There is an
      inverse relationship between the status of the relevant B-vitamins and the
      homocysteine blood concentration. Supplementation of these vitamins results in a
      significant reduction of the homocysteine level. Nutritive amounts seem to be
      sufficient to obtain this reduction, even in the case of elevated homocysteine
      levels.

PMID- 9659411
TI  - Calcium and osteoporosis.
AB  - Osteoporosis is a crippling disease that emerges as an important public health
      problem both in developed and developing countries including Brazil. The clinical
      condition is characterized mainly by loss of bone mineral mass in later life as
      the net result of complex physiological and environmental interacting factors
      during lifetime. Calcium intake appears as an obvious nutritional factor in the
      prevention of osteoporosis but its contribution is still not well established
      particularly when populations with different habitual levels of calcium intake
      are compared. In this section, we examine the role of calcium intake as affecting
      bone mineral density at different stages of development and with aging, with
      special attention to the possible stress on bone mass due to pregnancy and
      lactation. Nutritional studies demonstrate that, in general, adequate calcium
      intake during lifetime contributes to decrease the risk of osteoporosis. However,
      the long term effects on bone health of sub-adequate, but not very low, habitual
      calcium intakes during highly demanding physiological periods such as
      adolescence, pregnancy and lactation, are still largely unknown. Sub-adequate
      calcium intakes are probably common in Brazil.

PMID- 9659412
TI  - The stage of nutrition transition in different Brazilian regions.
AB  - The stage of nutrition transition in Brazil at the end of the 1980s was evaluated
      using the data from a nationwide cross-sectional anthropometry survey in Brazil
      in 1989 (Pesquisa Nacional sobre Saude e Nutricao-PNSN). Comparable estimates of
      undernutrition and obesity were produced for children from 6 to 35 months old (n
      = 3,641), adult males from 20 to 64 years old (n = 14,235) and adult females from
      18 to 64 years old (n = 15,669). Body Mass Index (kg/m2) was employed to assess
      both undernutrition and obesity in adults and weight-for-age (undernutrition) and
      weight-for-height (obesity) indices were used for children. The 5th and 95th
      centiles of the distribution of these indices in a reference population were used
      as limits for the diagnosis of undernutrition and obesity, respectively. Ordering
      the frequency of the problems in the population showed obesity in women and
      undernutrition in children to be the two main nutritional disorders in the
      country. These two problems are the most frequent in the urban population of the
      North, Northeast and Center-West regions, and in the Southeast and Center-West
      rural regions. Obesity leads among both adults and children in the urban areas of
      the Southeast and South regions, and in the rural South. Only in the rural
      Northeast, the poorest region in the country, undernutrition leads among
      children, men and women. This mosaic of situations determines the need for a
      complete reassessment of traditional nutrition policies and programs employed in
      the country.

PMID- 9659413
TI  - Changes in food consumption in Brazil.
AB  - Changes in eating habits have occurred in the last decades in several countries
      associated to demographic, economic, social and epidemiologic factors. In Brazil,
      the available data about food consumption are the result of Family Budget Surveys
      undertaken by Getulio Vargas Foundation and IBGE (Brazilian Institute of
      Geography and Statistics) in 1961/1963 and 1987/88, respectively, and the
      National Study of Family Expenditure (ENDEF), carried out by IBGE during 1974/75.
      They reveal as principal tendencies the decreasing consumption of staple
      foodstuffs (beans, rice, manioc flour), pork meat, lard and butter, the
      replacement of bovine meat for chicken, and the increase in the consumption of
      eggs, milk products and vegetable oils. Based on these surveys, the intake of
      macronutrients in urban areas showed a decrease of carbohydrate and an increase
      of fat contribution as sources of calories, an increase in the consumption of
      animal protein in detriment of vegetable protein, and substitution of animal fats
      for vegetable fats. It was also observed an increase in the use of industrialized
      foodstuffs, directly related to income, leading to a greater diversity of
      foodstuffs and lower consumption of staple foods. Recent studies with adult and
      elderly population from the city of Sao Paulo show a reduction in the consumption
      of fatty and fried foods and sugar, and an increase in the consumption of fruits
      and vegetables because of health concern. Studies that take into account the
      verified changes in eating habits and the new consumption tendencies, as well as
      their impact on nutritional and health conditions of the Brazilian urban
      population, are presently needed.

PMID- 9659414
TI  - Non-communicable diseases in Brazil: mortality patterns, morbidity studies and
      risk factors.
AB  - The aim of this presentation is to give an overview on non-communicable diseases
      in Brazil and to speculate about singular data that have been described in our
      country. The high rates of esophageal cancer, the elevated high blood pressure
      prevalence and some determinants of the decline of cardiovascular mortality are
      discussed more deeply.

PMID- 9659416
TI  - Prevalence and risk factors in iron deficiency and anemia.
AB  - Iron deficiency anemia is nowadays the world most prevalent nutritional problem.
      Several studies concerning anemia prevalence were carried out in Brazil with
      pregnant women and children aged less than 5 years, restricted mainly to
      northeast and southeast regions of the country. More recently, groups other than
      those of pregnant women and children aged less than 5 years, such as school
      children and adolescents, have become the target of those concerned with the
      issue. The differences found out among the groups and the diversity of
      methodologies employed, prevent us from reaching an evolutionary profile
      concerning nutritional anemia in Brazil. However, the high rates of prevalence
      verified by the various studies carried out are enough for justifying the general
      interest in controlling and/or eradicating the disease. This paper presents a
      model of causal determination of anemia, that points out the diet as the
      principal immediate factor. The typical Brazilian diet is poor in bioavailable
      iron. The two foods--meat and beans--responsible for the totality of this mineral
      in the habitual Brazilian diet have been registering a decreasing intake in the
      last decades. Iron deficiency is also observed in the food practice of infants
      and children aged less than 5 years. This situation justifying the urgency in
      finding an effective intervention to control this relevant nutritional problem.

PMID- 9659415
TI  - Micronutrient regulation in pregnant and lactating women from Rio de Janeiro.
AB  - Studies with low-income pregnant and lactating women from the city of Rio de
      Janeiro, concerned mainly with the changes in micronutrient homeostasis during
      pregnancy and lactation in the absence of overt clinical deficiencies, are
      reported. These studies focused on folate, cobalamin, iron, zinc and vitamin A.
      Factors that may affect the maternal micronutrient state, such as dietary
      intakes, use of supplements and interrelationships of micronutrients have been
      considered, as well as the implications of these changes for maternal-fetal
      transfer and milk composition. Although these studies were not designed to
      evaluate the prevalence of sub-clinical micronutrient deficiencies in pregnant
      and lactating women, they indicate that high frequencies of sub-clinical
      deficiencies of folate, iron, zinc and vitamin A, especially in pregnant women,
      are expected to be found in Rio de Janeiro.

PMID- 9659417
TI  - Zinc in urban infants and children from Brasilia.
AB  - The substandard living conditions of the poor families in the fast growing urban
      population of Brazilian cities puts children in the more vulnerable group of
      micronutrient deficiency. The chemical analysis of milk diets consumed by infant
      showed that zinc is insufficiently provided in bottle-fed infants, and possibly a
      first-limiting nutrient in breast-fed babies, at least during the first 6 months
      of life.

PMID- 9659418
TI  - Iron deficiency anemia in children: prevalence and prevention studies in Ribeirao
      Preto, Brazil.
AB  - Iron deficiency and ferropenic anemia are, certainly, the most prevalent and
      specific nutritional problems in Brazil. The Ribeirao Preto region is no
      exception to it. A large prevalence of iron deficiency/anemia is found, mainly in
      the age group 6-24 months. In spite of the fact that several aspects of its
      physiopathology are known it is a very difficult problem to be solved. Many
      approaches and alternatives for their prevention have been tried but we are far
      from controlling the situation. Several studies carried out at the Medical School
      of Ribeirao Preto, University of Sao Paulo, Brazil have shown this high incidence
      of iron deficiency and iron anemia among infants and preschool children. The
      importance of iron supplementation to preterm, premature and normal infants was
      pointed out. The possibility of use of iron complexes to prevent iron deficiency,
      besides the usual ferrous sulfate, was shown. Several community studies proved
      the feasibility of distribution and intake of iron as supplements or
      fortification of carriers as alternatives to prevent iron deficiency.

PMID- 9659419
TI  - Micronutrients and urban life-style: lessons from Guatemala.
AB  - Guatemala is a nation of 10 million persons, at the northern point of the chain
      of five Republics derived from Spanish colonies on the Isthmus of Central
      America. The country is diverse in its ethnicities, its climate and terrain, and
      its agricultural pursuits. The majority of its population is poor, illiterate,
      and under-employed. It has had a unique and turbulent political history, and only
      recently has emerged. The traditional basis of the diet, dating to Mayan times,
      is maize and beans. Guatemala City, with its population in excess of 2 million
      inhabitants, having doubled since the Earthquake of 1976, is the only major
      metropolis. The pattern of dietary selection and the format of eating meals is
      changing in relationship to the size, congestion, economic evolution, and
      modernization of the capital city. A wider selection of foods is consumed in the
      city, but preparation follows the traditions of the rural cuisine. Street vendors
      play an ever larger role in the feeding of the urban poor. Quantitative data are
      only available for vitamin A and zinc, and only in certain subsegments of the
      population. The vitamin A in fortified foods, notably table sugar which is
      fortified with retinyl palmitate by legal mandate, makes up over one-third of the
      intake. The maize tortilla is an important sources of calcium, iron, zinc and
      copper. Average zinc intakes are appropriate, but the biological availability of
      the metal is low. The intake of iodine is totally dependent upon table salt which
      is inconsistently fortified. Data on micronutrient status exists for vitamin A,
      iron, iodine, riboflavin and zinc. With respect to rural areas, no major
      advantages or disadvantages in the adequacy of micronutrient nutriture can be
      claimed for the urban population. It is possible that, in the metropolitan area,
      vitamin A nutriture is slightly better and riboflavin status somewhat poorer than
      in the countryside. The prospects for future directions in urban lifestyle, in
      micronutrient status and in their interaction are uncertain. The pressure of
      growth are straining the ability of the municipal infrastructure and the
      industrial base to respond with provision of services and employment.

PMID- 9659420
TI  - Micronutrient deficiency in urban Indonesia.
AB  - The economic situation of Indonesia is characterized by a large increase in the
      gross national product which has been on average 7% annually during the last ten
      years. This was accompanied by rapid urbanization. With the economic improvement,
      "First World" and "Third World" health and nutrition problems are coexisting in
      Indonesia. In 1992, the most common of death cause was cardiovascular disease
      whereas tuberculosis was the second ranking. About 40% of the preschool children
      are stunted. The main stable food and energy source is rice, although the urban
      population has a more diverse food pattern than the rural population. In Jakarta,
      many children receive too late colostrum feeding and mothers are not aware about
      the importance of correct breastfeeding practices after delivery. Three studies
      had shown that about one fifth of preschool children and one fourth of elderly
      take micronutrient supplements. Nevertheless, micronutrient deficiencies are
      prevalent in Jakarta. About one third of women suffer from moderate vitamin A
      deficiency (plasma retinol < 0.70 mmol/L) and 50% of pregnant women are anemic.
      More information is necessary on other micronutrient deficiencies. For example, a
      small study revealed that nearly two thirds of non-institutionalized elderly
      living in Jakarta experience thiamine deficiency. Appropriate interventions to
      reduce micronutrient deficiencies should sensitize the urban population to the
      fact that the government should restrict itself to use its resources to assist
      only the poorest individuals and groups, whereas it must be expected from the
      middle class to spend more time and money to solve their own problems.

PMID- 9659421
TI  - [Effect of a supplementary feeding program on height growth in children].
AB  - The general objective of this study was to compare the variation exhibited in
      height/age by a group of low income children (when they were under 2 years) who
      had a mild deficit in this parameter and who received an important supplement,
      with another group with the same deficit who did not receive it. To achieve this
      objective we obtained a sample of children who were beneficiaries of Chile's
      National Complementary Feeding Program. The experimental group included children
      from the so called reinforced component of that program and the control group
      from the basic one. The results showed that after 12 months of observation, both
      groups gained in height, being those increments statistically significantly.
      Interestingly, the improvement was greater in the control group. The authors
      argue that with the nutritional situation that our country exhibits presently,
      that is, a very small percentage of low wt/age and around 18% to 24% of low
      income children with a mild deficit in height, a general improvement of the
      family's economic status probably produces a larger effect on this indicator than
      a high calorie/protein supplement.

PMID- 9659422
TI  - [Anthropometric growth of the school population in rural and suburban areas of
      Durango, Mexico].
AB  - The nutritional status of school children from the rural and suburban areas from
      the state of Durango. Mexico, was determined using anthropometric evaluation,
      during the periods 92-93 and 93-94. The sample included a total of 1,033 school
      children, of which 504 were males and 529 females, ranging ages from 3 to 15
      years. The results of the study indicate that compared to the international
      standards, linear growth and weight of the Durango children decline with age and
      accentuate theirself through time. On the other hand, growth in body mass index
      exhibits a lesser retardation than that of height by age and weight by age.
      Evaluation of the weight by height index indicated that about 3% of the school
      children has suffered from chronic undernutrition.

PMID- 9659423
TI  - [The effect of lactation time on the macronutrient and mineral composition of
      milk from Venezuelan women].
AB  - Human milk is considered the ideal food for the infant and it has been
      extensively used to estimate its nutrient requirements. The objective of this
      paper was to determine the effect of lactation time on the macronutrient an
      mineral content of milks obtained from Venezuelan women and also to compare this
      with the established nutrient requirements of the infant. For this purpose 83
      milk samples from 45 low income mothers were analyzed at the colostrum (48 h to
      54 d) and mature states of lactation (1.3 and 6 months). The results showed that
      colostrum had a higher protein and a lower fat content than mature milks whereas
      its content of energy and carbohydrate was similar to mature milk. The iron and
      calcium content of the milk remained unchanged during the whole study whereas Zn
      and Cu decreased and increased with lactation time respectively. In contrast,
      phosphorous and magnesium increased up to 3rd month of lactation and remained
      constant there after. The macronutrient content of 850 ml of the analyzed milk
      almost completely fulfilled the daily infant requirements established in the US
      (RDA) and Canada (RNI). The mineral content of this volume of milk however was
      insufficient to cover the infants requirements particularly those established in
      the US. The most notorious deficiency in these milks was in Fe since they could
      fulfill only 11% the infants RDA for this mineral. The infant mineral
      requirements established in Canada are substantially lower than those defined in
      the US and therefore the analyzed milks could totally fulfill the Canadian infant
      daily requirements of Mg, Fe and Ca and more than 70% and 80% of the requirements
      of Zn and P. In general, the results of this study showed that the nutrient
      content of the analyzed milks agree well with those reported in the literature
      for women from different parts of the world including developed and
      underdeveloped areas. At the same time they pointed out the differences in the
      definition of the infant nutrient requirements set by different countries and
      also emphasize the fact that human milk, which by definition is the natural
      source of nutrients for the human infant apparently is incapable of fulfilling
      its daily requirements.

PMID- 9659424
TI  - Serum level of Zn, Cu and Fe in healthy schoolchildren residing in Merida,
      Venezuela.
AB  - Levels of Zn, Cu and Fe were measured in blood serum samples of 320 children: 160
      boys and 160 girls randomly selected, ages between 7 and 14 years, all considered
      healthy and residing in the City of Merida, Venezuela. The metals were determined
      using flow injection analysis-flame atomic absorption spectrometry. There was a
      tendency for serum Zn (SZn) to increase with age. There was no significant
      difference in SZn levels between males and females in the different age groups.
      Serum copper (SCu) decreases significantly (p < 0.05) with age in male children,
      whereas it increases in female children. The concentration of serum iron (SFe)
      tends to be lower than that reported in the literature. However, the age groups
      studied showed no statistically significant sex and age-related differences. The
      results are compared with values previously reported for healthy children studied
      in other communities. The present study has shown that there is a complex
      interaction between SZn, SCu, SFe and age and sex of the children. On the other
      hand, our observations also suggest that more detailed studies of these metals
      should be done, and that the study should include metabolic balances and
      associations between SZn, SCu, SFe and anthropometric variables (height, weight,
      body mass index and skinfold thickness).

PMID- 9659425
TI  - [Effect of microwaves over Staphylococcus aureus and Salmonella spp. inoculated
      into frozen minced meat].
AB  - The efficacy of the microwave oven in the destruction of some pathogenic
      microorganisms inoculated into minced meat was studied. These were inoculated
      with Salmonella spp. or Staphylococcus aureus, freezed for 2-3 days at -4 degrees
      C and thawed, according to their weight, in an Amana microwave (24450 Hz). They
      were radiated at levels of 60%, 70%, 80% and 90% for periods of 15, 45, 60, 90
      and 105 seconds. The rate of survival of each bacteria was determined according
      to the methodology described by Vanderzant and Splittstoesser, as well as the
      activity of the acid phosphate enzyme as cooking parameter. The microbiological
      analysis shows that, despite the cooking level used, the time required for the
      elimination of both bacteria is greater than the one in which the meat is
      considered enzymatically and organoleptically cooked.

PMID- 9659426
TI  - Evaluation of different solvent systems for the extraction and fractionation of
      oleoresins from guajillo peppers.
AB  - Dried guajillo peppers were first extracted with four different solvents:
      ethanol, acetone, ethyl acetate and hexane with the aim of obtaining oleoresins
      which were further fractionated into red and paprika extracts. Results showed
      that as the polarity of the solvent increased the amount of pigments extracted
      also increased. Acetone had good affinity for pungent (capsaicin) compounds.
      Utilization of these solvents alone did not produce red and paprika oleoresins
      that meet commercial specifications. Fractionation of acetone extracted
      oleoresins with ethanol: water (90:10) yielded a precipitate and a solution. The
      precipitate and solution produced red and paprika extracts that meet pungency and
      color specifications. It was possible to obtain red and paprika oleoresins from
      mild guajillo peppers.

PMID- 9659427
TI  - Tannin elimination and improvement of the digestibility of protein sorghum
      grains.
AB  - Three hybrids of sorghum grains [Sorghum bicolor (L) Moench] containing 3.8, 3.0
      and 0.2% of tannins were treated. Abrasive dehulling and storage of moist grains
      were tested separately and in combination to reduce the tannin content and to
      improve the nutritional quality of grains. The moisture content of the grains was
      increased from 12 to 30% by humidifying them with water, acetic acid, sodium
      bicarbonate or sodium hypochlorite solutions. Abrasive dehulling of the grains to
      a yield between 75 and 80%, humidifying the grains with acetic acid (1% v/v) and
      storing them during 7 days at 20 degrees C proved to be the most effective
      procedure. In this way tannin can be totally reduced and the in vitro
      digestibility of protein can be increased to 87.5%.

PMID- 9659428
TI  - [Antiphysiological and nutritional factor changes in sorghum (Sorghum bicolor
      (L.) Moench) seeds during germination].
AB  - The purpose of this work was to evaluate the effects of germination on the
      nutritional quality of two commercial varieties of low tannin content Sorghum:
      brown sorghum without testa (ICSY-CM89513) and white sorghum (ISIAP Dorado).
      After 24 hours of germination the condensed tannin concentration (catechin
      equivalent) was reduced 60% and 40% for brown and white sorghum respectively.
      However, tannin levels increased up 100% at 96 h germination. Phytic acid
      concentration decreased about 90% in 96 hours for both varieties. The lysine
      concentration increased up 110% (72 h germination) and 129% (48 h) for white and
      brown sorghum respectively. The thiamine, niacin and riboflavin contents
      increased 73, 200 and 353% respectively for brown sorghum in 72 h and 15, 44 and
      93% respectively for white sorghum in 48 h. The "in vitro" enzymatic
      digestibility was increased 39.3% (72 h) for brown sorghum and 100% for white
      sorghum. The albumin concentration increased 80% and 74% (72 h) for brown and
      white sorghum respectively. The Calculated Protein Efficiency Ratio indicated
      nutritional improvements with germination. The sprouting was a practical and
      simple process for providing better nutritional properties in sorghum seeds to be
      used as human food.

PMID- 9659429
TI  - [Quality of pastas supplemented with rice bran].
AB  - The objective of this research was to investigate the potential of using rice
      bran as an ingredient in pastas spaghetti type. Two of the pastas were made with
      semolina from durum as raw material, supplemented with 10 and 20% rice bran. The
      other two were made with granular flour and the same percentage of rice bran.
      Proximate composition of raw material was analyzed. Pastas were elaborated in a
      local industry. Composition, proximal, color, texture, and sensorial quality of
      pastas were determined. Protein content (13.9-15.0%), ash (1.47-3.09%) and
      dietary fiber (6.71-8.45%) of pastas increased according to the percentage of
      rice bran added. The hardest pastas were those elaborated with semolina from
      durum wheat and with a 10% of substitution. Also, they were the most yellow. The
      sensory panel found differences in quality among the pastas evaluated. Pastas
      with 10% rice bran had the best quality. The results demonstrated that is
      possible to elaborate pastas with 20% as maximum of rice bran resulting products
      with high protein, ash and dietetic fiber content, but some undesirable
      characteristics were given by the rice bran as white spots, wrinkles and color
      changes.

PMID- 9659430
TI  - [Cooking quality of pastas supplemented with rice bran].
AB  - The purpose of this study was to evaluate the quality during and after cooking of
      four pastas spaghetti type. Rice bran was used as ingredient in order to increase
      protein and dietetic fiber content. In two of the four formulation, semolina
      durum was supplemented with 10 and 20% rice bran. In the other two formulation
      granular flour was supplemented with 10 and 20% rice bran. Time cooking, water
      absorbtion, solid loss, color and hardness, (instrumental and sensory), Protein
      Efficiency Ratio (PER) and Apparent Digestibility in vivo were determined.
      Acceptability was evaluated by a 35-member consumer panel. Rice bran improved
      solid loss during cooking and increased cooking time, PERs were not affected
      significantly but Apparent Digestibility decreased when rice bran was increased.
      Sensory quality was affected because rice bran made pastas hard and dark but they
      were comparable to high fiber pasta existing in market.

PMID- 9659431
TI  - [Development of a soup pasta based on the taste and nutritional requirements for
      aged people].
AB  - The objective of this project was to elaborate a soup paste product based on
      cereal/leguminous mixture by cold extrusion method according to the preferences
      and limitations of the senescent population. Formulas were obtained by a
      computation food mixtures program; the limitations applied were: protein quantity
      and quality. Selected mixtures has to contain protein values over 13.2 g/100 g
      and a chemical assessment of leucine, lysine and methionine-cistein not lower
      than 75% of the FAO/OMS 1973 recommendations, because they are the limitant
      aminoacids of the amaranth, the wheat and the beans, respectively. Chemical,
      physical, microbiological, farinografics and sensorial tests were applied to
      evaluate the characteristics of the mixtures. The selected mixture was made up
      of: 70% wheat semolina (Triticum durum), 20% beans (Phaseoulus vulgaris L) and
      10% amaranth (Amaranthus hypochondriacus). The manufactured paste allowed 20% of
      the nutritional requirements of the elderly people of protein, carbohydrates,
      calcium, iron and vitamins A, B1 and C; it was highly accepted (95%) by the
      elderly people and was microbiologically stable for 12 weeks period at 25 degrees
      C and 55% RH in cellophane packages. We can conclude that the soup paste may be a
      vehicle to add substances and deficient nutriments to the habitual diet of the
      elderly people in our country.

PMID- 9659432
TI  - [A test to measure the degree of knowledge on food and nutrition at the onset of
      elementary school].
AB  - The objective of this work was to design a test to measure the degree of
      knowledge on food and nutrition in school-age children from elementary first and
      second grades. A graphic instrument was designed according to the psychological
      child development and was based on the specific objectives pursued by the
      curriculum programs of the Ministry of Education. The test was developed around
      the following topics through 15 items: Area 1: Basic Concepts on Food and
      Nutrition (9 items) and Area 2: Food, Personal and Environmental Hygiene (9
      items). The test was pilot tested on 103 school-age children of both grades
      (1:1), of both sexes (1:1), belonging to Penalolen and Las Condes counties from
      Chile's Metropolitan Region and from high and low socioeconomic status (SES)
      (1:1), measured through the Graffar's Modified Method. The final version of the
      test was applied in a representative sample of 1.482 school-age children from
      Chile's Metropolitan Region from elementary first and second grades during 1986
      1987. Content validity was assured by a team of judges and by the curriculum
      programs. Reliability was assessed by the Spearman correlation with the Spearman
      Brown correction. Item-test consistency was determined by the Pearson correlation
      coefficient. Data were processed by the statistical analysis system (SAS)
      package. Results showed that reliability coefficient was 0.84 and item-test
      consistency was equal or above 0.25 in all items. It can be concluded that this
      test can be useful to determine the degree of knowledge on food and nutrition at
      the onset of elementary school, both in Chile and in other countries.

PMID- 9659433
TI  - [Preferential habits of consumers of common bean (Phaseolus vulgaris L.) in
      Mexico].
AB  - A detailed knowledge of the consumer's preferences for the different classes of
      common bean is useful to define objectives in bean breeding and quality projects
      in a given region or country and it is also a valuable tool to design marketing
      strategies. The present work consisted on the application of a survey to 1514
      common bean consumers in 14 states of Mexico. To facilitate the interpretation of
      the results the country was divided in four regions: North East, North West,
      Center and South. In the North West region, 98% of the surveyed individuals eat
      the "Azufrado" types (sulphur yellow); in the North East, 70% of the consumers
      prefer "pinto" (beige with brown mottles) and "Bayo" (cream) types; in the South,
      90% of the consumers prefer the "Black" type; and in the Center of the country,
      all commercial classes are consumed. Within a commercial class, specific
      characteristics are demanded. For instance, in the black type, small and opaque
      seeds are preferred while in the "Flor de mayo" (Beige with pink mottles) type
      medium to large seeds having bright seed coat are preferred. The main
      characteristics utilized by consumers to select a given bean type are cooking
      time and flavor. It was observed that preferential classes are well established
      among the consumers since 70% responded that they would not change the preferred
      class even if the alternative class was sold to a lower price. Consumers do not
      soak the beans, because it changes the flavor and the aspect of the cooked beans
      and they do not add salt at the beginning of the cooking process due to the same
      reason. Organoleptic studies conducted in the laboratory confirmed that soaking
      of beans or addition of salts in the soaking water or at the beginning of the
      cooking process negatively affected acceptability of cooked beans by panelists.
      In this paper aspects related to ways of processing and consuming common beans as
      well as marketing aspects are discussed.

PMID- 9659434
TI  - The starch and total sugar content of Mexican fruit and vegetables.
AB  - The starch and total sugar contents of 20 types of fruit, 28 types of vegetables
      and six different herbs, grown in Mexico, were analysed. The selection was based
      on dietary surveys to identify those foods most widely consumed. Starch was
      determined by an enzymatic method whilst total sugar was determined
      gravimetrically. The foods were grouped according to the Southgate
      classification. Fruits contained little starch (range 0-4 g/100 g fresh weight
      (FW) except in the case of the plantain (31 g/100 g FW starch), whereas
      vegetables showed a higher concentration with tubers in the range 10-20 g/100 g
      FW starch. Legumes contained 0-5 g/100 g FW; amongst the capsicum group the
      chilli poblano had the highest concentration at 1.3 g/100 g FW starch. The
      concentration of sugars in fruits ranged from 0.6 g/100 g FW to 21.1 g/100 g FW.

PMID- 9659435
TI  - [Fatty acid content of sausages manufactured in Venezuela].
AB  - The moisture and lipid content as well as the fatty acid composition of sausages
      were determined. Lipids were extracted and purified with a mixture of
      cloroform/methanol 2:1. Fatty acids in the lipid extract were methylated with 4%
      sulfuric acid/methanol solution and later were separated as methyl esters by gas
      liquid cromatography (GLC). Sausages presented a lipid content between 7.10% for
      canned sausages and 35.23% for the cocktail type. Most of the fatty acids were
      monounsatured with oleic acid as the major component with values between 42.54%
      for ham sausage and 48.83% for francfort type. Satured fatty acids followed, with
      palmitic acid as the major component in a range between 21.46% and 26.59% for
      bologna and Polaca sausage respectively. Polyunsaturated fatty acids were present
      in less quantities with concentration of linoleic acid between 8.5% (cotto salami
      type) and 12.60% (cocktail type). Turkey and poultry sausages presented a higher
      content of polyunsaturated and less saturated fatty acids than the other types of
      sausages studied.

PMID- 9659436
TI  - A wild vetchling's ominous tendrils gone to the loins.

PMID- 9659437
TI  - Tumor necrosis factor in CHF: a double facet cytokine.

PMID- 9659438
TI  - Dietary arginine and the prevention of cardiovascular diseases.

PMID- 9659439
TI  - Weight watching in cardiology: low molecular weight heparin for acute coronary
      syndromes.

PMID- 9659440
TI  - Experimental evidence for proarrhythmic mechanisms of antiarrhythmic drugs.
AB  - The major limitation to antiarrhythmic drug therapy is the risk of arrhythmia
      promotion, or 'proarrhythmia.' This complication may be lethal, and greatly
      restricts the value of antiarrhythmic agents, particularly for arrhythmias
      without an intrinsic mortality risk, such as atrial fibrillation. In order for
      improved antiarrhythmic drug therapy to be developed, it is essential to
      understand the fundamental mechanisms that cause proarrhythmic reactions to
      antiarrhythmic drugs. The present article reviews the experimental evidence that
      has been obtained regarding the mechanisms of proarrhythmia. The evidence
      available provides important insights, and points to potential strategies for
      developing newer and safer antiarrhythmic compounds.

PMID- 9659441
TI  - Peptidic regulation of heart rate and interactions with the autonomic nervous
      system.
AB  - Autonomic influences on the heart rate have been the subject of intense research
      for many decades and are classically devoted to the sympathetic and
      parasympathetic systems. However, developments over the past few years in our
      knowledge of the organization of the autonomic nervous system have led to the
      conclusion that in addition to the classical transmitters, peptidic transmitters
      are clearly present and have direct or indirect actions on cardiac conduction.
      Neuropeptides have been found to collocate with each other or with classical
      transmitters, thereby increasing the variety of chemical signals that a neuron
      can utilize to communicate with other cells. Neuropeptides can act as
      neurotransmitters, neuromodulators or neurohormones. Some are produced in
      endocrine glands and circulate as hormones, while others are contained in cardiac
      myocytes, neurons, or endothelial cells in proximity to the sinoatrial node and
      can therefore act in a paracrine or autocrine way on the pacemaker cells to
      modulate heart frequency. There is evidence supporting such a role, especially
      for locally situated neuropeptide Y, vasoactive intestinal peptide, calcitonin
      gene-related peptide, substance P, angiotensin II, natriuretic peptides,
      endothelins and possibly many others. The role of the peptidic neurotransmitters
      in the conduction system should not be exaggerated. Nevertheless, neuropeptides
      certainly represent a new category of neurotransmitters forming a third component
      of the autonomic nervous system and may have complex actions with potential
      therapeutic implications in man.

PMID- 9659442
TI  - AGEs and their interaction with AGE-receptors in vascular disease and diabetes
      mellitus. I. The AGE concept.
AB  - OBJECTIVE: This is the first part of a bipartite review that summarizes the
      rising knowledge on the molecular mechanisms underlying the action of advanced
      glycation endproducts (AGEs) and their contribution to diabetic complications and
      vascular disease. While the first part presented here focusses on AGE formation,
      the second part will describe the AGE-protein/receptor interactions and their
      role in mediating AGE-dependent intracellular signalling. RESULTS: Nonenzymatic
      glycation, in which reducing sugars are covalently attached to free amino groups
      and ultimately form AGEs, has been found to occur during normal aging and at
      accelerated rate in diabetes mellitus. Oxidation, accompanying glycation in vivo,
      further supports chemical modifications. AGE formation and protein crosslinking
      are irreversible processes that alter the structural and functional properties of
      proteins, lipid components and nucleic acids. AGE modifications do not only
      change the physicochemical properties of the afflicted molecules, but also induce
      cellular signalling, activation of transcription factors and subsequent gene
      expression in vitro and in vivo. CONCLUSIONS: AGEs elicit a wide range of cell
      mediated responses that might contribute to the pathogenesis of diabetic
      complications, vascular and renal disease and Alzheimer's disease. Substances
      that inhibit AGE formation, reduce oxidative stress or destroy already formed
      crosslinks may limit the progression of disease and may offer new tools for
      therapeutic interventions in the therapy of AGEs mediated disease.

PMID- 9659443
TI  - An estimate of fetal autonomic state by spectral analysis of human umbilical
      artery flow velocity waveforms.
AB  - OBJECTIVE: Determination of gestational age-related fluctuations in heart rate in
      the umbilical artery of the early human fetus. METHODS: Doppler velocity
      recordings from human umbilical artery were obtained, in a cross-sectional study
      design in 137 singleton pregnancies at 10-20 weeks of gestation. After exclusion
      criteria were applied, data on 117 normal pregnancies were available and
      subdivided into group I: 10-12 weeks (n = 49); group II: 13-16 weeks (n = 43);
      and group III: 17-20 weeks (n = 25). Blood flow velocity waveforms were
      reconstructed from Doppler audio signals. Variability in heart rate was
      calculated using Fast Fourier Transforms (FFT). Individual heart rate variability
      power spectra were subdivided into frequency bands. RESULTS: Fetal heart rate
      variability decreases at 10-20 weeks and demonstrates a shift to lower
      frequencies at 17-20 weeks. CONCLUSIONS: Fetal heart rate variability is related
      to gestational age and shows a shift to lower frequencies which may reflect
      autonomic functional development.

PMID- 9659444
TI  - Expression of calcium regulatory proteins in short-term hibernation and stunning
      in the in situ porcine heart.
AB  - BACKGROUND: Myocardial hibernation and stunning are characterised by a reversible
      contractile dysfunction during and after ischaemia, respectively. Calcium
      homeostasis might be disturbed in hibernation and stunning due to altered
      expression of cardiac proteins involved in calcium handling. METHODS: In
      enflurane-anaesthetised swine the coronary blood flow through the left anterior
      descending coronary artery was decreased to reduce regional contractile function
      (microsonometry) by approximately 50%. In transmural biopsies obtained during
      ischaemia and reperfusion creatine phosphate as well as the expression of
      sarcoplasmic reticulum calcium ATPase (SERCA), phospholamban (PLB), calsequestrin
      (CSQ), and troponin inhibitor (TnI) were determined. RESULTS: During ischaemia
      creatine phosphate, after an initial reduction, recovered back to control values,
      and necrosis was absent (hibernation). After 90 min of ischaemia the myocardium
      was reperfused for 120 min but regional contractile function continued to be
      depressed (stunning). PLB, SERCA, CSQ, and TnI proteins were unchanged during
      ischaemia as well as reperfusion. Likewise, levels of PLB and SERCA mRNAs were
      unchanged. CONCLUSION: It is concluded that other mechanisms than altered
      expression of these regulating proteins underlie the contractile dysfunction
      observed during acute ischaemia, short-term hibernation and stunning.

PMID- 9659445
TI  - Long acting calcium antagonist amlodipine prevents left ventricular remodeling
      after myocardial infarction in rats.
AB  - OBJECTIVE: The purpose of this study was to examine the effect of amlodipine, a
      long-acting calcium antagonist, on the left ventricular remodeling, including
      systolic and diastolic dysfunction, the change of cardiac gene expression in the
      myocardial infarcted rats (MI). METHODS: On the first day after myocardial
      infarction, the animals were randomly assigned to amlodipine treatment (n = 8) or
      untreated groups (MI; n = 9). We then performed Doppler-echocardiographic
      examinations and measured the hemodynamics at four weeks after myocardial
      infarction. Following these measurements, their cardiac mRNA was analyzed.
      RESULTS: Left ventricular end-diastolic pressure (LVEDP) and central venous
      pressure (CVP) increased to 22 +/- 1 mmHg and 5 +/- 1 mmHg. Amlodipine reduced
      LVEDP and CVP to 15 +/- 1 mmHg (P < 0.01) and 3 +/- 0 mmHg (P < 0.01). The weight
      of right ventricle in MI was significantly larger than in the control rats
      (Control; 0.48 +/- 0.01 g/kg, MI; 0.79 +/- 0.04 g/kg, P < 0.01). Left ventricular
      end-diastolic dimension (LVDd) in MI increased to 10.3 +/- 0.3 mm (P < 0.01)
      (Control; 6.2 +/- 0.3 mm). Amlodipine prevented an increase of the weight of
      right ventricle (0.62 +/- 0.03 g/kg, P < 0.01) and LVDd (7.9 +/- 0.2 mm, P < 0.01
      to MI). The rats in MI showed systolic dysfunction shown by the decreased
      fractional shortening (Control; 31 +/- 2% versus MI; 15 +/- 1%, P < 0.01), and
      diastolic dysfunction shown by E wave deceleration rate (Control; 18.1 +/- 2.0
      m/s2, MI; 32.6 +/- 2.1 m/s2, P < 0.01). Amlodipine significantly prevented
      systolic and diastolic dysfunction. The increases in beta-MHC, alpha-skeletal
      actin, and ANP mRNAs in the non-infarcted left ventricle and right ventricle at
      four weeks after the myocardial infarction were all significantly suppressed by
      the treatment with amlodipine. On the other hand, depressed alpha-MHC was
      restored to normal levels by amlodipine in both regions. CONCLUSIONS: Amlodipine
      prevents the left ventricular remodeling process accompanied by systolic and
      diastolic dysfunction, and inhibits abnormal cardiac gene expression after
      myocardial infarction.

PMID- 9659446
TI  - Effects of the novel antiarrhythmic agent azimilide on experimental atrial
      fibrillation and atrial electrophysiologic properties.
AB  - OBJECTIVES: This study was designed to evaluate how the atrial
      electrophysiological and antiarrhythmic effects of azimilide compare with those
      of the specific rapid delayed rectifier (IKr) blocker dofetilide. BACKGROUND:
      Azimilide, a new class III drug, was initially believed to be a highly selective
      blocker of the slow delayed rectifier (IKs), but recent studies suggest that
      azimilide potently blocks IKr. Thus, it has been suggested that azimilide's in
      vivo effects may simply be due to IKr blockade. METHODS: Dose regimens producing
      stable effects over time were developed, and two dose levels of azimilide (10 and
      then 20 mg/kg) or dofetilide (0.08 and then 0.16 mg/kg) were administered to
      morphine/chloralose-anesthetized dogs during sustained vagal atrial fibrillation
      (AF). Epicardial mapping was used to measure conduction velocity and AF cycle
      length. RESULTS: Azimilide terminated AF in 13/14 dogs (93%), while dofetilide
      terminated AF in 6/12 (50%, P < 0.05). While dofetilide had strong reverse use
      dependent effects on atrial ERP (e.g. at lower doses, dofetilide increased ERP by
      51 +/- 3% at a basic cycle length, BCL, of 400 ms and by 17 +/- 3% at a BCL of
      200 ms), azimilide's effects on ERP were rate-independent (ERP increased at lower
      dose by 38 +/- 6%, BCL 400 ms; 35 +/- 10%, BCL 200 ms). Neither drug affected
      conduction. CONCLUSIONS: Azimilide is effective against experimental AF, and
      increases ERP with a frequency dependence different from the IKr blocker
      dofetilide, suggesting that azimilide's actions on atrial tissue cannot be
      attributed exclusively to IKr block, and that effects on other currents (such as
      IKs) are likely to be important.

PMID- 9659447
TI  - Flow-function relations during graded coronary occlusions in the dog: effects of
      transmural location and segment orientation.
AB  - OBJECTIVE: The sensitive relationship between regional myocardial perfusion and
      local systolic deformation during acute myocardial ischemia is not independent of
      the transmural location or segment orientation. The aim of this study was to
      determine the effects of fiber orientation and transmural location on the
      relationships between regional myocardial flow and three-dimensional systolic
      wall strain during graded coronary artery occlusions. METHODS: Transmural
      distributions of three-dimensional strain (by biplane radiography of implanted
      radiopaque markers) and myocardial blood flows (using fluorescent microspheres)
      were measured in the ischemic region during graded left anterior descending (LAD)
      coronary artery occlusions in 12 anesthetized dogs. RESULTS: Occlusion of the
      coronary artery did not significantly alter mean heart rate or end-systolic
      pressure. As flow decreased during graded occlusions, ischemia significantly
      changed systolic circumferential, longitudinal, radial, fiber and cross-fiber
      strains (p < 0.004). There was a significant effect of transmural position on
      circumferential, cross-fiber and radial strains, but not on fiber or longitudinal
      strains. Ischemia significantly altered all normal strains: circumferential,
      longitudinal, fiber, cross-fiber and radial. There was a strong interaction
      effect between transmural location and blood flow for circumferential, cross
      fiber and radial strains, but not fiber or longitudinal strains. CONCLUSION:
      During non-transmural ischemia, there is evidence of strong transmural tethering
      in the cross-fiber direction, whereas the fiber-strain flow relation is
      independent of transmural position. Thus, whether the relationship between local
      myocardial bloodflow and systolic strain during acute ischemia is dependent on
      transmural location, depends on segment orientation.

PMID- 9659448
TI  - Efficacy of a beta-adrenergic receptor antagonist, propranolol, in preventing
      ischaemic ventricular fibrillation: dependence on heart rate and ischaemia
      duration.
AB  - OBJECTIVES: To investigate the prevention of ventricular fibrillation with a beta
      adrenergic receptor (beta-AR) antagonist in anaesthetized, open-chest pigs in a
      model of ischaemia, intended to reproduce what happens either in anginal attack
      or in the first hour of infarction. METHODS: Ventricular fibrillation threshold
      (VFT) was determined with trains of diastolic stimuli of 100 ms duration
      delivered by a subepicardial electrode inserted in the area subjected to
      ischaemia. Ischaemia was obtained by the complete occlusion of the left anterior
      descending coronary artery, either near its origin during brief but increasing
      periods (30, 60, 90, 120, 150, 180, 240, 300 s), or half-way from its origin for
      a much longer time (more than 60 min). RESULTS: During transient proximal
      occlusion and isoprenaline infusion (0.25 microgram/kg/min), propranolol (50
      micrograms/kg plus 2 micrograms/kg/min) attenuated both tachycardia and the fall
      in VFT to 0 mA. The shortening of MAP duration accompanying depolarization of the
      fibres was concurrently slowed down, and time to fibrillation prolonged (122 +/-
      15 to 262 +/- 14 s, p < 0.001). In the absence of isoprenaline infusion,
      propranolol exerted similar effects, but to a lesser degree, in proportion to
      heart rate dependent on sympathetic activity. In contrast, it became unable to
      raise VFT before and during ischaemia, when heart rate was kept constant by
      pacing. After persistent midportion occlusion, significant differences in VFT
      were found only at the 5th min, depending on whether heart rate was accelerated
      by isoprenaline (0.8 +/- 0.2 mA), left normal (1.8 +/- 0.3 mA) or slowed down by
      propranolol (1.6 +/- 0.3 mA). Later on, especially after 15 and 25 min of
      ischaemia, VFT, which was below 1.0 mA, did not appear to be influenced by the
      activation or blockade of beta-ARs: spontaneous fibrillations were observed in
      the same number in this period with or without the administration of propranolol.
      Beyond 30 min after occlusion, the rise in VFT, subsequent to the first
      irreversible cell damage, also occurred in the same way. CONCLUSIONS: The
      prevention of ischaemic ventricular fibrillation by a beta-AR antagonist, judged
      from VFT, is easily checked experimentally when ischaemia is only transitory,
      especially if sympathetic activity is high. The maintenance of VFT at a
      relatively high level is essentially related to the depressant effect on the
      sinus rate. The same animal model does not give support to an effective
      protection in the first hour of infarction. However, the control of heart rate
      may also be beneficial in these circumstances by attenuating systemic
      haemodynamic disorders.

PMID- 9659449
TI  - The low molecular weight heparin, enoxaparin, limits infarct size at reperfusion
      in the dog.
AB  - OBJECTIVE: Heparin (HEP) is used in the post-thrombolytic state to prevent vessel
      reocclusion, thereby aiding myocardial salvage. Side effects limit its benefits,
      but besides anticoagulant activity HEP has diffuse actions that may be
      potentially beneficial to jeopardized reperfused myocardium. This study compares
      the effect of therapeutic doses of HEP and enoxaparin (ENOX), a low molecular
      weight heparin, and to streptokinase (SK), on infarct size. METHODS: The left
      anterior descending coronary artery was occluded in dogs for 90 min, followed by
      6 h of reperfusion with a residual critical stenosis in place. Five min before
      reperfusion, HEP (2800 IU) was injected i.v., and perfused at 500 IU/h until
      sacrifice in group 2, while groups 3 and 4 received ENOX (2128 anti-Xa IU i.v.)
      followed by 380 anti-Xa IU/h. Group 4 was also given 500,000 IU SK over 30 min
      before reperfusion beginning at 55 min of occlusion (ENOX + SK), while group 5
      received only SK. Controls (CON, group 1) received saline. P-selectin mediated
      platelet-neutrophil rosettes formation was also tested in vitro in the presence
      of HEP and ENOX. RESULTS: The area at risk delimited by dye perfusion was
      statistically similar among groups. Covariance analysis between infarct size (%
      of area at risk) delimited with triphenyltetrazolium and collateral flow measured
      with radioactive microspheres confirmed that groups given ENOX (21.6 +/- 5.5%)
      and ENOX + SK (24.9 +/- 3.9%) developed smaller infarcts (P < 0.05) than CON
      (48.1 +/- 4.5%), as opposed to HEP (32.2 +/- 3.6%) and SK (46.8 +/- 3.4%) groups.
      111In-platelet counts in the infarct were reduced significantly by 64% in the
      ENOX group as compared to CON, and to a lesser extent (42%, n.s.) in the ENOX +
      SK group, but were not reduced by HEP and SK treatments. Neutrophil accumulation
      in the infarcts was decreased significantly and by more than 75% in the ENOX and
      ENOX + SK groups versus CON, but not in the HEP and SK groups. Also, only ENOX
      (10-100 micrograms/ml) significantly inhibited platelet-neutrophil rosettes
      formation in a plasmatic milieu. CONCLUSIONS: The ENOX treatment, as opposed to
      that of HEP, reduces myocardial platelet and neutrophil accumulations, and limits
      infarct size when given just before and during reperfusion. The benefits of ENOX
      on infarct size were not modified by SK, and may be related, at least in part, to
      an interaction with P-selectin-mediated cell adhesion.

PMID- 9659450
TI  - Elevation of an endogenous inhibitor of nitric oxide synthesis in experimental
      congestive heart failure.
AB  - OBJECTIVE: NG,NG-dimethylarginine (asymmetric dimethylarginine, ADMA) is an
      important endogenous substance with potent inhibitory actions on nitric oxide
      (NO) synthesis. The present study was designed to determine circulating ADMA
      levels and endothelium-dependent, NO mediated vasodilation in a rat model of
      congestive heart failure (CHF). METHODS: CHF was induced in rats by coronary
      artery ligation. Sham-operated rats served as normal controls. Plasma ADMA was
      determined by high performance liquid chromatography with fluorescence detection.
      Glomerular filtration rate (GFR) and renal blood flow (RBF) were measured by the
      clearance of inulin and p-aminohippuric acid, respectively. Endothelial function
      of the aorta was assessed in an organ bath. RESULTS: Plasma levels of ADMA in
      rats with CHF (0.94 +/- 0.05 mumol/l) were significantly increased compared with
      sham-operated controls (0.75 +/- 0.06 mumol/l, p < 0.05). Plasma levels of ADMA
      was negatively correlated with GFR (r = -0.65, p < 0.05). Decreased endothelium
      dependent relaxation to acetylcholine in the aorta of CHF was completely restored
      by L-arginine (300 microM) (p < 0.01) while endothelium-independent relaxation to
      nitroprusside was not altered. ADMA potently inhibited endothelium-dependent
      relaxation in thoracic aorta of normal and CHF rats. The effect of ADMA was
      completely antagonized by L-arginine in both groups (p < 0.01). Moreover, L
      arginine improved endothelium-dependent relaxation in CHF rats in the presence of
      ADMA. CONCLUSIONS: An endogenous NO synthesis inhibitor ADMA is increased in the
      circulation of rats with CHF. The increased plasma levels of ADMA may contribute
      to the decreased endothelium-dependent relaxation in CHF, which is restored by L
      arginine, possibly by competitive antagonism of ADMA.

PMID- 9659451
TI  - Guanylyl cyclase inhibition reduces contractility and decreases cGMP and cAMP in
      isolated rat hearts.
AB  - OBJECTIVE: Several studies have shown that increasing cGMP in the heart reduces
      contractility, however, decreasing basal cGMP levels have also been shown in some
      studies to reduce contractility. This study was designed to evaluate the
      hypothesis that decreasing basal levels of cGMP decreases ventricular
      contractility, and that this depressed function is associated with a decrease in
      cAMP. METHODS: Using paced, constant flow, buffer-perfused rat hearts, we
      determined the effects of intracoronary infusions of the guanylyl cyclase
      inhibitor, LY83583 (10(-5) M), on ventricular function, oxygen consumption, and
      ventricular content of cGMP and cAMP. These experiments were conducted in the
      absence and presence of isoproterenol (ISO) to increase baseline left ventricular
      developed pressure (LVDP) and cAMP. RESULTS: LY83583, infused for 25 min,
      decreased LVDP by 44 +/- 3 (SE), 77 +/- 20 and 120 +/- 38 mmHg, in control, 10(
      9) M, and 10(-8) M ISO-stimulated hearts, respectively. Regardless of the level
      of ISO stimulation, LY83583 reduced LVDP to the same sub-basal level. Oxygen
      consumption also decreased, but proportionately less than LVDP. ISO increased
      cAMP without changing cGMP. LY83583 decreased cGMP by about 25% at all levels of
      ISO, and decreased cAMP by 22% in the 10(-8) M ISO-stimulated group. CONCLUSION:
      Guanylyl cyclase inhibition by LY83583 decreased cGMP, cAMP and ventricular
      contractility. However, LY83583 depression of contractility was not always
      associated with a reduction in cAMP, suggesting that LY83583 can depress
      contractility by both cAMP-dependent and independent mechanisms.

PMID- 9659452
TI  - Efficacy of myocardial initial reperfusion with 2,3 butanedione monoxime after
      cardioplegic arrest is time-dependent.
AB  - OBJECTIVE: In a previous study, initial reperfusion of isolated hearts after
      cardioplegic arrest with 2,3 butanedione monoxime (BDM) for 5 min was markedly
      superior to warm hyperkalemic reperfusion in improving the initial oxygen balance
      and reducing reperfusion arrhythmias. However, left ventricular contractility was
      only marginally enhanced. The goal of the present study was to test, wether the
      efficacy of BDM reperfusion can be enhanced by prolonging the application period.
      METHODS: 32 Langendorff perfused guinea pig hearts were subjected to 50 min of
      cardioplegic arrest in St. Thomas Hospital II solution at 37 degrees C for 50
      min. Control hearts (n = 8) were immediately reperfused with normal Krebs
      solution for 30 min. In BDM-5, BDM-20, and BDM-40 hearts (n = 8, each), a 5, 20,
      or 40 min period of initial BDM reperfusion preceded perfusion with normal Krebs.
      RESULTS: BDM markedly improved the O2 balance during initial reperfusion by
      reducing O2 demand by over 50% (p < 0.01) in all treatment groups while coronary
      flow was maintained. Reperfusion contracture, estimated by the end-diastolic
      balloon pressure was inhibited by more than 50% in BDM-20 and BDM-40 hearts.
      Recovery of left ventricular developed pressure, dP/dtmax, and -dP/dtmax was
      significantly enhanced throughout the reperfusion period only in the BDM-20 group
      (p < 0.05). Myocardial ultrastructure was best preserved in BDM-20 hearts.
      CONCLUSIONS: 20 min of initial BDM reperfusion were clearly superior to immediate
      Krebs reperfusion or a shorter (5 min) or longer (40 min) BDM treatment period in
      attenuating reperfusion damage. Thus, contraction uncoupling during initial
      reperfusion by BDM or similarly acting drugs may prove a viable technique to
      reduce myocardial reperfusion damage in patients undergoing open heart surgery.

PMID- 9659453
TI  - Oxidant stress with hydrogen peroxide attenuates calcium paradox injury: role of
      protein kinase C and ATP-sensitive potassium channel.
AB  - OBJECTIVE: We tested the hypotheses that low concentration of H2O2 attenuates the
      Ca2+ paradox (Ca2+ PD) injury, and that activation of protein kinase C (PKC)
      and/or ATP-sensitive potassium channel (KATP) are involved in the protective
      effects of H2O2. METHODS: Langendorff-perfused rat hearts were subjected to the
      Ca2+ PD (10 min of Ca2+ depletion followed by 10 min of Ca2+ repletion).
      Functional and biochemical effects of H2O2 and other interventions on the cell
      injury induced by the Ca2+ PD were assessed. RESULTS: In the Ca2+ PD hearts
      pretreated with 20 mumol/l H2O2, left ventricular end-diastolic pressure and
      coronary flow were significantly preserved. Furthermore, peak lactate
      dehydrogenase release was significantly decreased and ATP contents were more
      preserved, compared with non-treated Ca2+ PD hearts. H2O2-treated hearts also
      showed remarkable preservation of cell structure. Addition of a specific PKC
      inhibitor, chelerythrine during H2O2 treatment completely abolished the
      beneficial effects of H2O2 on the Ca2+ PD. Similarly, an activator of PKC.
      Phorbol 12-myristate 13 acetate mimicked the protection by H2O2. Furthermore,
      pretreatment with a KATP opener, cromakalim also provided protection similar to
      H2O2 against the Ca2+ PD injury. However, a specific KATP inhibitor,
      glibenclamide was not able to completely block the effects of H2O2. CONCLUSIONS:
      These findings suggest that pretreatment with low concentration of H2O2 provides
      significant protection against the lethal injury of Ca2+ PD in rat hearts. PKC
      mediated signaling pathways appear to play a crucial role in the protection
      against the Ca2+ PD injury.

PMID- 9659454
TI  - Effect of protein kinase C inhibitors on cardioprotection by ischemic
      preconditioning depends on the number of preconditioning episodes.
AB  - OBJECTIVES: This study examined the possibility that the role of PKC in
      [corrected] PC, and thus the response to PFC inhibitors, may differ depending on
      how many ischemic episodes are employed to precondition the heart. METHODS: In
      the first series of experiments, myocardial infarct was induced by 30 min of
      coronary occlusion and 3 h of reperfusion in the rabbit. Infarct size was
      determined by tetrazolium staining and expressed as a percentage of area at risk
      (%IS/AR). Prior to the 30-min ischemia, rabbits were subjected to no PC, single
      PC (i.e., PC with an episode of 5 min ischemia/5 min reperfusion), and repetitive
      PC (2 cycles of 5 min ischemia/5 min reperfusion) with or without one of three
      treatments: polymyxin B (PolyB), staurosporine (Stauro), and 8
      sulfophenylthephylline (SPT). In the second series of experiments, the rabbits
      received 5 min of coronary occlusion after repetitive PC with or without PolyB or
      Stauro treatment. Then, myocardial tissue in the ischemic region was sampled for
      assay of PKC activity. Untreated rabbits served as controls. RESULTS: Single and
      repetitive PC limited %IS/AR to the same extent (%IS/AR = 9.8 +/- 1.9 and 10.4 +/
      2.3, both p < 0.05, vs. the control value of 44.5 +/- 3.4), and single PC was
      blocked by PolyB (%IS/AR = 43.9 +/- 2.7) and Stauro (%IS/AR = 31.5 +/- 3.2).
      Although the protocol of PolyB injection maintained the plasma PolyB level during
      sustained ischemia well above its Ki for PKC, this agent and also Stauro failed
      to abolish the protection by repetitive PC (%IS/AR = 21.6 +/- 3.0 and 11.4 +/-
      4.3, respectively). SPT, an adenosine receptor antagonist, not only blocked
      single PC (%IS/AR = 44.4 +/- 4.4) but also attenuated protection by repetitive PC
      (%IS/AR = 28.3 +/- 3.6). Infarct sizes in non-preconditioned hearts were not
      modified by PolyB, Stauro, or SPT. The ratio of membrane fraction PKC activity to
      cytosolic fraction PKC activity was elevated by repetitive PC plus 5 min
      ischemia, and this change in PKC was inhibited in hearts given PolyB and Stauro.
      CONCLUSIONS: In contrast to single PC, repetitive PC protects the heart against
      infarction even when PolyB and Stauro are administered to inhibit PKC during
      ischemic insult. This difference may be attributable to a PKC-independent
      mechanism, in which the adenosine receptor may be partly involved.

PMID- 9659455
TI  - Stimulation of Ca-induced Ca release only transiently increases the systolic Ca
      transient: measurements of Ca fluxes and sarcoplasmic reticulum Ca.
AB  - OBJECTIVE: To investigate the effects of stimulating calcium induced Ca release
      with low concentrations (100-200 microM) of caffeine and, in particular, to study
      the cellular mechanisms responsible for the transient responses found previously.
      METHODS: Experiments were performed on isolated rat ventricular myocytes.
      Intracellular calcium concentration ([Ca2+]i) was measured with Indo-1, the cells
      were voltage-clamped with the perforated patch technique and sarcoplasmic
      reticulum (s.r.) Ca content was estimated from the integral of the caffeine
      evoked current. RESULTS: The systolic Ca transient produced by the first
      depolarization in the presence of caffeine was larger than the control. Over the
      next few pulses the magnitude of the Ca transient returned to control levels
      despite the maintained presence of caffeine. The s.r. Ca content was decreased by
      9% after one pulse in caffeine and by 21% after several pulses in caffeine. The
      first pulse in the low concentration of caffeine was followed by an enhanced
      inward (Na-Ca exchange) current tail indicating increased efflux of calcium from
      the cell. The extra loss of calcium calculated from the tail current agreed
      quantitatively with that from the change of s.r. Ca content. CONCLUSIONS: These
      results show that stimulating calcium induced calcium release produces only a
      transient increase of the systolic Ca transient. This is due to the larger Ca
      transient decreasing the s.r. Ca content. It is concluded that any agent whose
      sole mode of action is stimulation of calcium-induced calcium release will not
      produce a maintained inotropic effect. The consequences of this for the effects
      of other modulators of calcium induced calcium release are discussed.

PMID- 9659456
TI  - Stimulation of P2Y receptors activates c-fos gene expression and inhibits DNA
      synthesis in cultured cardiac fibroblasts.
AB  - OBJECTIVES: The aims of this study were to determine (1) whether neonatal rat
      cardiac fibroblasts (CAFB) express P2Y receptors; (2) whether CAFB respond to
      extracellular ATP by inducing expression of c-fos mRNA; and (3) whether
      extracellular ATP modulates norepinephrine (NE)-stimulated cell growth in CAFB.
      METHODS: Expression of P2Y1 and P2Y2 receptors and induction of c-fos were
      examined by Northern blot analysis. CAFB growth was assessed by measuring
      [3H]thymidine incorporation and DNA content. P2Y receptor pharmacology was
      studied using various ATP analogues. RESULTS: Northern blot analysis of polyA
      enriched RNA confirmed that at least 2 subtypes of P2Y receptors (P2Y1 and P2Y2)
      are expressed in cultured CAFB. Extracellular ATP induced the expression of c-fos
      mRNA through a pathway that was sensitive to inhibitors of protein kinase C
      (PKC), but not to inhibitors of intracellular Ca2+ signaling. Extracellular ATP
      inhibited the NE-stimulated increases in DNA content and in [3H]thymidine
      incorporation into DNA. Whereas the potency order for stimulation of c-fos
      expression was ATP = UTP > ADP > adenosine, the potency order to inhibit the NE
      induced increase of [3H]thymidine incorporation into DNA was ATP > ADP > UTP >
      adenosine. CONCLUSIONS: These data demonstrate that CAFB express both P2Y1 and
      P2Y2 receptor mRNA and that CAFB respond to P2Y receptor stimulation by induction
      of c-fos and inhibition of DNA synthesis. These findings suggest that the effects
      of ATP on [3H]thymidine incorporation into DNA and on expression of c-fos mRNA
      are exerted via distinct P2Y receptor subtypes.

PMID- 9659457
TI  - High-density lipoprotein particles are large in patients with variant angina.
AB  - OBJECTIVE: Dyslipidemia in patients with coronary vasospasm may be characterized
      by low level of high-density lipoprotein (HDL)-cholesterol as well as
      apolipoprotein (apo) A-I but not high level of low-density lipoprotein
      cholesterol. This study sought to examine the HDL particle size in patients with
      variant angina. METHODS: The HDL particle size was examined by analyzing serum
      lipid levels in 38 patients with variant angina to compare with those of 40
      control subjects and 30 normocholesterolemic patients with stable effort angina.
      Also, actual HDL size distribution was assessed by electrophoresis. RESULTS: The
      HDL-cholesterol, apoA-I and apoA-II levels were all lower (P < 0.01 for each) in
      patients with variant angina and patients with stable effort angina as compared
      with control subjects. The apoA-II level was lower (P < 0.01) in patients with
      variant angina than in patients with stable effort angina. The apoA-I/apoA-II
      ratio was lower (P < 0.01) in patients with stable effort angina, but not in
      patients with variant angina as compared with control subjects. In contrast, the
      HDL-cholesterol/apoA-I ratio was higher in patients with variant angina than in
      control subjects (P < 0.01) and also patients with stable effort angina (P <
      0.01). The slope of the regression line, comparing HDL-cholesterol and apoA-I
      levels, was greater in patients with variant angina than in control subjects (P <
      0.05) and patients with stable effort angina (P < 0.05), suggesting an increase
      in larger HDL particles. Native polyacrylamide gel electrophoresis revealed that
      HDL particles in patients with variant angina were skewed towards larger sizes
      compared with control subjects (P < 0.01) and patients with stable effort angina
      (P < 0.01). The abnormal serum lipid values were normalized in the patients with
      variant angina after the medical treatment and inactivation of the coronary
      spasm. CONCLUSION: High HDL-cholesterol/apoA-I levels associated with low serum
      HDL-cholesterol and apoA-I levels were characteristic in patients with variant
      angina, in whom HDL particles were large, cholesterol-rich and possibly
      malfunctioning.

PMID- 9659458
TI  - Impairment of endothelium-dependent vasorelaxation in experimental
      atherosclerosis is dependent on gender.
AB  - OBJECTIVE: Nitric oxide (NO) has been suggested to have antiatherosclerotic
      effects. It has also been demonstrated that there is a greater basal release of
      endothelium derived relaxing factor (EDRF) in female as compared to male rabbit
      aorta, which also might have beneficial effects in atherosclerosis. We thus
      sought to determine if gender influences the severity of atherosclerosis.
      METHODS: We studied 18 female and 18 male New Zealand White rabbits that were
      randomly divided in two groups of 9 animals each and fed either a standard or a
      cholesterol diet (0.75%) for 15 weeks. RESULTS: In cholesterol-fed rabbits the
      percentage of atherosclerotic lesions in the aorta was identical in females and
      males and was inversely correlated with the maximal aortic relaxation to
      acetylcholine as assessed in organ chamber experiments (females: P < 0.0008,
      males: P < 0.0002). Importantly, the cholesterol diet induced a significantly (P
      < 0.025) more severe impairment of maximal vasorelaxation to acetylcholine in
      males from 78.4 +/- 1.2% to 29.4 +/- 10.2%) compared to females (from 84.4 +/-
      1.2% to 60.7 +/- 8.5%). Both male gender (P < 0.0001) and the extent of
      impairment of endothelium-dependent relaxation (P < 0.0002) were associated with
      a reduced aortic sensitivity to S-nitroso-N-acetyl-D,L-penicillamine, which
      releases NO into the organ bath. In contrast, the aortic sensitivity to the
      organic nitrates pentaerythritol tetranitrate and isosorbide 5-nitrate, which
      release NO after enzymatic metabolization within the smooth muscle, was not
      reduced. CONCLUSIONS: These results suggest that the impairment of endothelium
      dependent vasorelaxation induced by atherosclerosis is dependent on gender. This
      may be due to a greater degradation of extracellular NO in the vessel wall of
      males.

PMID- 9659459
TI  - Interaction between isoniazid and diverse vasodilators: role of decreased
      cerebral GABA.
AB  - OBJECTIVE: To determine if the interaction between isoniazid and hydralazine,
      consisting of increased hypotension accompanied by bradycardia, occurs with other
      vasodilators. METHODS: Blood pressure and heart rate responses to a number of
      vasodilators were determined in rats under chloralose-urethane, pretreated or not
      with 250 mg/kg of isoniazid. The influence of this dose of isoniazid on GABA
      levels in the hypothalamus and pons-medulla was assessed in other groups of rats.
      RESULTS: Increased hypotension and bradycardia following i.p. isoniazid were
      observed with dipyridamole, prazosin, pinacidil and hydralazine given i.v.
      Bradycardia without increased hypotension appeared with papaverine and verapamil,
      while increased hypotension with unchanged heart rate was observed with minoxidil
      and captopril. Isoniazid decreased GABA in the hypothalamus and pons-medulla.
      CONCLUSIONS: At the high dose used, isoniazid interacts with various
      vasodilators, irrespective of their mechanism of action. The interaction could be
      due to the influence of the drug on GABA levels at cardiovascular regulatory
      sites.

PMID- 9659460
TI  - Chronic dietary supplementation with L-arginine inhibits platelet aggregation and
      thromboxane A2 synthesis in hypercholesterolaemic rabbits in vivo.
AB  - OBJECTIVES: L-arginine exerts anti-atherosclerotic effects in
      hypercholesterolaemic rabbits via modulating endogenous NO production. We
      investigated whether L-arginine inhibits thromboxane formation in vivo and
      platelet aggregation ex vivo in this animal model. METHODS: The urinary excretion
      rates of 2,3-dinor-6-keto-PGF1 alpha (major urinary metabolite of PGI2) and 2,3
      dinor-TXB2 (major urinary metabolite of thromboxane A2) were used as indicators
      of platelet-endothelial cell interactions in vivo. Rabbits were fed 1%
      cholesterol (Cholesterol group, N = 8), 1% cholesterol plus 2.25% L-arginine
      (Cholesterol + L-arginine, N = 8), or normal rabbit chow (Control, N = 4) for 12
      weeks. Urine samples were collected in weekly intervals. At the end of the study
      period platelet aggregation ex vivo and endothelium-dependent and -independent
      vascular function of isolated aortic rings in vitro was assessed. RESULTS:
      Urinary 2,3-dinor-TXB2 excretion significantly increased in the cholesterol group
      (p < 0.05), and endogenous NO formation (measured as urinary nitrate excretion)
      decreased (p < 0.05). Both parameters were significantly correlated with each
      other (R = 0.48, p < 0.01). L-arginine partly restored urinary nitrate excretion
      and significantly reduced TXA2 production to values even below those in the
      control group (p < 0.001). Urinary 2,3-dinor-6-keto-PGF1 alpha excretion
      increased in early hypercholesterolaemia and returned to control values in the
      second half of the study period. The early increase in urinary 2,3-dinor-6-keto
      PGF1 alpha excretion was attenuated by L-arginine. Platelet aggregation was
      significantly enhanced in cholesterol-fed rabbits and attenuated by dietary L
      arginine. L-arginine also improved the impaired endothelium-dependent relaxations
      to ADP, and normalized the vasoconstrictor effects of 5-HT in isolated aortic
      rings. CONCLUSIONS: Cholesterol-feeding enhances platelet aggregation and TXA2
      formation, and stimulates platelet-endothelial cell interaction in rabbits. These
      effects are probably due to impaired NO elaboration, as indicated by decreased
      urinary nitrate excretion. Chronic dietary supplementation with L-arginine
      elevates systemic NO elaboration and significantly increases the PGI2/TXA2 ratio.
      It thus beneficially influences the homeostasis between vasodilator and
      vasoconstrictor prostanoids in vivo.

PMID- 9659461
TI  - The ETA receptor antagonist, BMS-182874, reduces acute hypoxic pulmonary
      hypertension in pigs in vivo.
AB  - OBJECTIVE: Elevated levels of the potent vasoactive peptide endothelin (ET), have
      been found in pathophysiological conditions associated with pulmonary
      hypertension. In this study, we have investigated the effects of the ETA receptor
      antagonist, BMS-182874, on hypoxic pulmonary hypertension in pigs. METHODS: Pigs
      were subjected to acute, intermittent 15-min periods of hypoxia (FiO2 0.1).
      Following a first hypoxia establishing hypoxic baseline values, vehicle or BMS
      182874 (10 or 30 mg/kg) was administered i.v. before a second hypoxic period. In
      separate groups of animals, the effects of the nitric oxide synthase inhibitor N
      omega-nitro-L-arginine (L-NNA) in combination with BMS-182874 (10 mg) during
      repeated hypoxia were investigated. The ET-1-blocking properties of BMS-182874
      were studied in vivo by infusion of ET-1 during normoxia and in vitro using
      isolated porcine pulmonary arteries. RESULTS: The hypoxia-evoked increase in mean
      pulmonary artery pressure was reduced by administration of BMS-182874 (10 mg/kg
      i.v.; from 42 +/- 8 to 34 +/- 4 mmHg, P < 0.05 and 30 mg/kg i.v.; from 38 +/- 4
      to 30 +/- 5 mmHg, P < 0.05). In addition, BMS-182874 at 30 mg/kg reduced the
      pulmonary vascular resistance during hypoxia (from 7.4 +/- 1.5 to 5.3 +/- 1.1
      mmHg.min.l-1 P < 0.05). The hemodynamic response to repeated hypoxia was
      reproducible in control animals and unaffected by the cyclo-oxygenase inhibitor
      diclophenac (3 mg/kg). Infusion of L-NNA alone resulted in an augmented pulmonary
      vasoconstriction during hypoxia; pulmonary arterial pressure from 35 +/- 6 to 43
      +/- 9 mmHg; P < 0.05 and vascular resistance from 7.2 +/- 1.1 to 9.9 +/- 1.8
      mmHg.min.l-1; P < 0.05. L-NNA in combination with BMS-182874 (10 mg/kg) resulted
      in a hypoxic pulmonary vasoconstriction of similar magnitude as hypoxic baseline.
      In addition, BMS-182874 reduced the hemodynamic response to ET-1 in normoxic pigs
      and competitively antagonized the vasoconstrictor effect of ET-1 in isolated
      porcine pulmonary arteries. CONCLUSIONS: The non-peptide, selective ETA receptor
      antagonist, BMS-182874, reduces hypoxic pulmonary vasoconstriction in pigs. The
      reduction in pulmonary vascular response to hypoxia following BMS-182874 is at
      least partly independent of nitric oxide.

PMID- 9659462
TI  - Vasodilator dysfunction in aged spontaneously hypertensive rats: changes in NO
      synthase III and soluble guanylyl cyclase expression, and in superoxide anion
      production.
AB  - OBJECTIVE/METHODS: Genetic hypertension is associated with an apparent
      endothelial dysfunction and impaired endothelium-dependent vasodilatation in
      response to increased flow and receptor-dependent agonists. However, the link
      between impaired vasodilatation and nitric oxide (NO) synthase expression is
      still unclear. In the present study, dilator responses were determined in the
      aorta and coronary circulation of 16 month old spontaneously hypertensive (SHR)
      and Wistar Kyoto rats (WKY). Changes in vascular reactivity were compared with
      alterations in superoxide anion production as well as endothelial NO synthase
      (NOS III) and soluble guanylyl cyclase expression. RESULTS: In the isolated
      perfused heart both the bradykinin- and sodium nitroprusside-induced vasodilator
      responses were attenuated in SHR compared to WKY. Western blot analysis revealed
      a parallel reduction in NOS III expression in coronary microvascular endothelial
      cells from SHR. Superoxide anion production in aortae from SHR was markedly
      elevated over that of aortae from WKY, and was almost completely abolished by
      pretreatment with superoxide dismutase. Superoxide dismutase induced similar
      relaxations in phenylephrine-preconstricted aortic rings from both SHR and WKY,
      but failed to restore the attenuated acetylcholine- and sodium nitroprusside
      induced relaxations in SHR. No difference in NOS III expression was detected in
      the aortae from either strain whereas soluble guanylyl cyclase expression was
      markedly decreased in SHR. CONCLUSIONS: These results demonstrate that NOS III
      expression in different tissues is differentially affected by hypertension.
      Moreover, although an elevated superoxide anion production is apparent in the
      aorta, a reduced soluble guanylyl cyclase expression appears to account for the
      observed vasodilator dysfunction in SHR.

PMID- 9659463
TI  - K(+)-induced dilation of a small renal artery: no role for inward rectifier K+
      channels.
AB  - OBJECTIVE: To investigate the mechanism of K(+)-induced vasodilation in a small
      artery from the kidney, with a particular emphasis on the role of inward
      rectifier K+ channels. METHODS: Lumen diameter and isometric tension recordings
      have been made from rabbit renal arcuate artery using pressurised- and wire
      myography respectively. In addition, conventional whole-cell and amphotericin
      perforated patch whole-cell recordings have been made from single smooth muscle
      cells isolated from the vessel. RESULTS: Arcuate arteries dilated when the
      extracellular K+ concentration was raised to 8-10 mM from either zero or a normal
      physiological level of about 6 mM. The effect was not endothelium-dependent.
      Application of 0.01-1 mM Ba2+ to block inward rectifier K+ channels had no
      significant effect on K(+)-induced vasodilation in the arcuate artery, but under
      the same experimental conditions K(+)-induced dilation of the rat posterior
      cerebral artery was abolished by Ba2+. In the presence of 60 mM extracellular K+,
      inward rectifier K(+)-current was detectable in some single smooth muscle cells
      isolated from arcuate arteries but on average the current density was low (-1.44
      pA pF-1 at -60 mV). K(+)-induced vasodilation of the arcuate artery was abolished
      by 10 microM ouabain and the half-effective concentration of K+ which induced
      vasodilation was 0.9-1.5 mM. CONCLUSIONS: The observations suggest that an
      increase in the extracellular K+ concentration (up to about 10 mM) dilates the
      rabbit renal arcuate artery and that the primary mechanism underlying the effect
      may be stimulation of Na(+)-K+ ATPase in the smooth muscle cell membrane. Inward
      rectifier K+ channels have a low average density in smooth muscle cells isolated
      from arcuate arteries and play no significant role in K(+)-induced vasodilation.

PMID- 9659464
TI  - Enhancement of the vasorelaxant potency of nicorandil by metabolic inhibition and
      adenosine in the pig coronary artery.
AB  - OBJECTIVE: Nicorandil is used clinically to treat angina and acts in part by
      opening ATP-sensitive K+ channels whose opening is also enhanced by metabolic
      compromise. We have therefore investigated whether treatments that mimic
      conditions in ischaemia can increase the potency of nicorandil to dilate coronary
      arteries. METHODS: Ring segments from pig small coronary arteries were mounted on
      a myograph, contracted with 20 mM K+ Krebs solution containing 200 nM BAYK 6844,
      and relaxations to cumulative doses of nicorandil were measured. RESULTS AND
      CONCLUSIONS: Nicorandil produced a dose-dependent relaxation with a mean pEC50 (
      log EC50, M) of 4.76 +/- 0.02. Inhibition of metabolism with carbonyl cyanide m
      chlorophenyl hydrazone (CCCP, 100 nM) or by removal of extracellular glucose
      significantly increased the potency of nicorandil (pEC50s of 5.11 +/- 0.08 and
      5.08 +/- 0.06, p < 0.05 in each case). The adenosine analogue 2-chloroadenosine
      (2-CA, 300 nM) had a similar effect (pEC50 = 5.17 +/- 0.06, p < 0.05). Reducing
      extracellular pH to 6.8 also significantly increased the potency of nicorandil,
      but to a smaller extent. Glibenclamide reduced the potency of nicorandil (pEC50 =
      3.81 +/- 0.01, n = 7), and abolished its enhancement by CCCP, zero glucose, 2-CA
      or pH 6.8 solution. 2-CA did not affect the potency of nicorandil in relaxing
      contractions to 80 mM K+ or the potency of glyceryl trinitrate. We conclude that
      the potency of nicorandil to cause coronary vasorelaxation is increased under
      conditions of metabolic inhibition. This effect appears to result from the K+
      channel opening action of the drug, and may have significant consequences for its
      therapeutic effectiveness.

PMID- 9659465
TI  - Mapping of vascular dendritic cells in atherosclerotic arteries suggests their
      involvement in local immune-inflammatory reactions.
AB  - OBJECTIVE: We previously demonstrated that vascular dendritic cells (VDCs) are
      present in the intima of large arteries and that their numbers are increased in
      atherosclerotic lesions. This study was undertaken to determine whether VDCs are
      involved in immune-mediated reactions in atherogenesis. METHODS: Specimens of
      carotid artery and aorta were obtained at operation. VDCs were identified with
      anti-CD1a or with S-100. Co-localisation of VDCs with different intimal cells,
      including T-cells and macrophages, was studied using a double immunostaining
      procedure. In areas where the co-localising cells were detected, the
      peculiarities of expression of HLA-DR, ICAM-1, VCAM-1 were examined. RESULTS: In
      all the atherosclerotic plaques, VDCs were seen in contact with T-cells, but
      these co-localising cells were irregularly distributed and were mainly found in
      zones of neovascularisation containing inflammatory infiltrates. In other areas,
      T-cell/VDC co-localisation was rarely detected but VDCs were often found in
      contact with macrophages. VDCs were detected also in the media beneath
      atherosclerotic lesions and in the adventitia, where they were mostly around vasa
      vasorum, especially in areas exhibiting signs of acute inflammation. In these
      areas VDCs expressed ICAM-1, VCAM-1 and were in contact with T-cells. In both
      plaques and in the adventitia, the areas with co-localising VDCs and T-cells
      corresponded to the areas with HLA-DR expression. CONCLUSIONS: The results
      suggest that VDCs are involved in T-cell activation in atherogenesis. There are
      two regions within the arterial wall where VDC/T-cell co-localisation mostly
      occurs, namely, in zones of neovascularisation containing inflammatory
      infiltrates located within atherosclerotic lesions, and in areas with
      inflammatory infiltrates around vasa vasorum in the adventitia. Possibly, some
      intimal VDCs migrate through the media and adventitia to adjacent lymph nodes
      where they present atherosclerosis associated antigens. We also speculate that
      VDC/macrophage contacts are essential in processing immune information in
      atherogenesis.

PMID- 9659466
TI  - Comparative reactivity and mechanical properties of human isolated internal
      mammary and radial arteries.
AB  - OBJECTIVE: The aim of this study was to analyse the arterial wall mechanics and
      the vasoreactive properties of the radial artery in comparison with those of the
      internal mammary artery and to discuss their implications for coronary bypass
      grafts. METHODS: Measurements of pressure and diameter were obtained from
      cylindrical segments, whereas measurements of reactivity were obtained from ring
      segments from the same arteries. We used an echo-tracking technique of high
      resolution enabling to investigate, in vitro, the diameter and the wall thickness
      of arterial cylindrical segments. Furthermore, the compliance, distensibility and
      incremental elastic modulus of the radial and of the mammary arteries were
      determined for a wide range of transmural pressure (0-200 mmHg) in presence and
      absence of norepinephrine (NE). RESULTS: Our results show that NE caused
      vasoconstriction of the two arteries. Strain was found significantly higher for
      the radial artery than for the internal mammary artery at any given value of
      stress both in the presence and in the absence of NE. In presence of NE,
      compliance for radial artery, in the overall transmural pressure range, did not
      change, whereas, distensibility was significantly increased and the elastic
      modulus was significantly decreased. Under the same conditions, the
      distensibility of the mammary artery tended to decrease and its elastic modulus
      to increase. In parallel, the vasoreactive properties of the two arteries
      confirmed the previous results showing that radial artery developed a significant
      higher tension to vasoconstricting agents (KCl, NE and phenylephrine (PHE)) and
      higher relaxation to isradipine than internal mammary artery. Moreover, radial
      artery displayed a lesser sensitivity to sodium nitroprusside than internal
      mammary artery. Furthermore, sensitivity to NE was found to be 7-fold higher for
      radial artery than for internal mammary artery. CONCLUSION: Taken together, data
      on the mechanical and reactive properties of radial and internal mammary arteries
      show why the radial artery displayed a higher potential for spasm than the
      internal mammary artery and why the use of Ca2+ channel blocker can decrease the
      incidence of occlusion and spasm.

PMID- 9659467
TI  - Monocyte-vascular smooth muscle cell interaction enhances nitric oxide
      production.
AB  - OBJECTIVE: The adhesive interaction of monocytes and vascular smooth muscle cells
      (VSMCs) has been suggested to be a regulatory signal in the cellular activation
      that is involved in the pathogenesis of atherosclerosis. We investigated the
      effects of monocyte-VSMC interaction on inducible nitric oxide (NO) synthase
      expression. METHODS: NO production by the cultured cells was determined by
      measuring the nitrite content of the culture media using the Griess reagent. The
      expression of inducible NO synthase protein was assayed by Western blotting.
      RESULTS: Interleukin-1 beta (IL-1 beta) induced nitrite production by VSMCs in a
      time-dependent manner. The addition of the mouse monocyte cell line J774 to IL-1
      beta-stimulated VSMCs further increased nitrite production in a monocyte number
      dependent manner. Enhanced nitrite production by coculture was accompanied by
      increased inducible NO synthase protein accumulation. Addition of tumor necrosis
      factor-alpha (TNF-alpha) also enhanced IL-1 beta-induced nitrite production by
      VSMCs, but TNF-alpha showed no effect in the presence of monocytes. Coculture of
      monocytes and VSMCs in the presence of IL-1 beta secreted substantial amounts of
      TNF-alpha. The production of nitrite by coculture was markedly inhibited by an
      anti-TNF-alpha antibody. CONCLUSIONS: The present study revealed that direct cell
      to-cell interaction between monocytes and VSMCs enhances NO production,
      suggesting an important role for their interaction in the pathogenesis of
      atherosclerosis.

PMID- 9659468
TI  - Soluble E-selectin and soluble intercellar adhesion molecule-1 in coronary artery
      disease.

PMID- 9659469
TI  - 'Comments on circulating transforming growth factor beta 1 and coronary artery
      disease'.

PMID- 9659470
TI  - Growth hormone in cardiovascular medicine.

PMID- 9659471
TI  - Are lateral X-rays useful in the treatment of fractures of the fourth and fifth
      metacarpals?
AB  - During initial and follow-up evaluation of fractures of the fourth or fifth
      metacarpal, X-rays in PA and oblique pronated views are taken. Routine straight
      lateral X-rays are also often made in the expectation that they will reveal
      additional information. The additional value was evaluated of 408 lateral X-rays
      taken of fourth and fifth metacarpal fractures in 160 conservatively treated
      patients. No clinically relevant information would have been missed if lateral X
      rays had been made selectively. Routine X-rays during treatment of these
      fractures should initially be limited to PA and oblique pronated views. Only
      after confirmation of a proximal comminuted fracture or signs of a pronounced
      anteroposterior dislocation, is an additional lateral X-ray indicated.

PMID- 9659472
TI  - Functional taping of fractures of the 5th metacarpal results in a quicker
      recovery.
AB  - Fractures of the fifth metacarpal can be treated non-operatively by plaster
      immobilisation or functional taping. In order to evaluate the better treatment
      policy, the two methods were compared in a prospective randomised series. We
      treated 25 patients with an ulnar gutter plaster-cast splintage and 25 with
      functional tape. Functional recovery was evaluated after one week and four weeks,
      three months and six months. Mobility, power-grip, pulling- and torque strengths
      were measured. The change in fracture angulation was calculated at the one and
      four-week follow-up. Residual symptoms were evaluated after six months. The
      functional tape group showed significant earlier functional recovery. After six
      months, there were no significant differences between the groups with regard to
      functional and anatomical results or the number of patients with residual
      symptoms. In both groups, we noted a change in fracture angulation only in those
      fractures that had been reduced. We conclude that fractures of the 5th metacarpal
      are better treated by functional taping than by cast immobilisation.

PMID- 9659473
TI  - Percutaneous endoscopic gastrostomy for patients with severe cerebral injury.
AB  - Early enteral nutrition improves the outcome of severely injured patients. To
      provide enteral nutrition, various methods are available. In a restrospective
      study we analysed the outcome of 24 severely traumatized patients (mean ISS =
      44), in whom a percutaneous endoscopic gastrostomy (PEG) was used for enteral
      nutrition. All patients had been admitted to the intensive care unit with major
      cerebral injury. The mean duration of intensive care treatment and the in
      hospital stay were 28 and 71 days, respectively. PEG was introduced 14 days after
      hospital admittance. Enteral nutrition through the PEG was administered for 45
      days. Four patients died, 8 patients were discharged from the hospital while
      being fed via the PEG and 12 patients resumed normal feeding and the PEG was
      removed. Three severe complications occurred; 1 patient aspirated massively and
      died; in 2 patients intra-abdominal leakage of the enteral nutrition occurred.
      Both patients recovered from this complication. We conclude that because of the
      advantages of early enteral nutrition on the one hand and the drawbacks of
      nasogastric feeding tubes on the other, in injured patients with severe cerebral
      damage, PEG placement is justified, despite the risk of complications.

PMID- 9659474
TI  - A high risk group for thoracolumbar fractures.
AB  - Unconscious patients with multiple injuries present a major diagnostic and
      therapeutic problem. The incidence of neurological deficit increases if diagnosis
      of a spinal injury is delayed or missed. Thoracolumbar fractures are commonly the
      result of high energy injuries and in an unconscious patient the risk of missing
      such fractures is increased considerably. There is little consensus on which
      blunt trauma patients warrant thoracolumbar spine films when no pain, tenderness,
      neurological deficit or cervical spine injuries are identified. We present a
      retrospective analysis of all patients who were admitted to the Major Injuries
      Unit at the Birmingham General Hospital and underwent radiological survey of the
      thoracolumbar spine. Of the 110 patients, all spinal fractures were detected in
      94 patients with a Glasgow Coma Scale (GCS) > or = 11. Of the 16 with a GCS < or
      = 10, 9 patients had sustained injuries of their thoracolumbar spine 4 of which
      were not detected initially due to a decreased level of consciousness. The common
      features amongst the 4 patients with missed injuries were: (1) High velocity
      injury. (2) Decreased level of consciousness on admission. (3) Associated head
      injury. (4) Pelvis/lower extremity injury. We describe the four cases and
      identify a group of high risk patients for thoracolumbar fractures. Radiological
      examination of the thoracolumbar spine is essential in this group.

PMID- 9659475
TI  - Surgical treatment of post-traumatic pelvic deformities.
AB  - Two patients with nonunion and malunion of an unstable pelvic fracture,
      presenting with pain and gait abnormality, were successfully treated with a
      pelvic reconstruction. The surgical repair consisted of a three staged procedure
      to perform the osteotomy, the reduction and the internal fixation. Both patients
      were satisfied with their outcome and experienced no complications.

PMID- 9659476
TI  - The use of non-absorbable suture in the fixation of patellar fractures: a
      preliminary report.
AB  - We describe the use of a non-absorbable, braided, polyester suture, 5 Ti-Cron
      (Davis and Geck, Gosport, Hampshire), for the fixation of patellar fractures as
      an alternative to stainless steel wire. Seven patients had their fractures fixed
      with this material and all progressed to union with good restoration of knee
      function. The ease of use of the suture allowed accurate reduction of the
      fractures and reduced operative and tourniquet time. None of the patients
      suffered significant complications from the procedure although two patients
      required removal of the suture because of knot symptoms. This was easily
      performed under local anaesthetic on an out-patient basis. We believe that non
      absorbable suture is a good substitute for stainless steel wire and reduces the
      need for a second procedure for wire removal.

PMID- 9659477
TI  - Magnetic resonance assessment of inversion ankle injuries in children.
AB  - A cohort of ten children with X-ray negative inversion ankle injuries were
      studied using Magnetic Resonance Imaging. The images obtained were scored on six
      pathological criteria. Despite all ten having normal plain radiographs, 50 per
      cent were found to have direct evidence of growth plate injury. Seventy per cent
      of the cohort had periosteal elevation including all those with evidence of
      growth plate injury. This study supports previous work which suggested that
      children with 'X-ray' negative acute inversion ankle injuries who exhibited the
      clinical signs of injury to their lower fibular growth plate most probably have
      an undisplaced Salter-Harris Type 1 fracture of this structure, despite normal
      radiographs.

PMID- 9659478
TI  - The mechanical 'quality' of osteophytes.
AB  - Intrinsic mechanical properties of osteophytes have been compared with those of
      normal articular cartilage by obtaining force-indentation curves. The cartilage
      of the osteophyte was found to be thinner than articular cartilage. The mean
      stiffness of osteophytes was 272.8 (+/- 78.8) N/mm and the mean stiffness of
      articular cartilage was 1412 (+/- 917.3) N/mm.

PMID- 9659479
TI  - Intact autocrine activation and cytokine production by PMNs from injured adults
      with elevated Candida antigen titres.
AB  - Injured patients with Candida antigen titres have increased mortality due to
      sepsis. Polymorphonuclear leucocytes (PMNs) from injured patients with elevated
      Candida antigen titres demonstrate impaired function against Candida albicans
      growth when compared with PMNs from injury matched controls. To determine if PMN
      dysfunction is global, PMNs from patients with positive Candida antigen titres
      were evaluated for their ability to activate the anticandidal function of normal
      PMNs (autocrine activation) and to produce tumour necrosis factor (TNF) and
      interleukin 8 (IL8), known activators of PMN anticandidal function, this study
      demonstrates that the PMN dysfunction is not global, as PMN cytokine production
      and autocrine activation remain intact.

PMID- 9659480
TI  - Arthroscopic debridement of external fixator pin tracts.
AB  - Major external fixator pin tract infection can be managed by curettage,
      overdrilling or excision of the pin tract. An alternative is arthroscopic
      debridement which allows thorough curettage with the advantage of direct
      inspection of the pin tract to ensure clearance of all necrotic tissue from the
      tract base and walls. To date, arthroscopic pin tract debridement has been used
      successfully to manage 25 pin tracts in six patients. Adequate visualization of
      the pin tract throughout its course was possible in all cases. Two patients
      subsequently underwent intramedullary nailing without complication. No recurrent
      infection has occurred at review at 13 months.

PMID- 9659481
TI  - Structure and process components of trauma care services in Israeli acute-care
      hospitals.
AB  - In recent years a vigorous effort has been made to improve primary trauma care in
      Israel. The Ministry of Health and other authorities have invested in new
      facilities in various hospitals which are engaged in trauma care. A survey was
      conducted in order to identify deficiencies in organization, personnel and
      equipment required to provide optimal trauma care. A cross-country survey was
      conducted by using a questionnaire that dealt with structure and process
      components of trauma care. The questionnaire was submitted to medical directors
      of emergency departments in all 24 acute-care hospitals in Israel. Additional
      information was obtained by a telephone poll when required. Inter-hospital
      variation concerning structure of trauma services, protocols and qualification of
      manpower responsible for primary care of the injured was found. The conclusions
      are that an increase in homogeneity in the field of trauma care is still needed.
      A continuous effort should be made in order to structurally and functionally
      further develop independent trauma units in all hospitals in Israel. Methods
      should be found to encourage young physicians to enter the field of trauma care.
      The establishment of a nationwide trauma registry system will undoubtedly
      contribute to future improvement in the initial care of the injured in Israel.

PMID- 9659482
TI  - Cutting-out of the lag screw after internal fixation with the Asiatic gamma nail.
AB  - Sixty consecutive intertrochanteric femoral fractures were treated with the
      Asiatic gamma nail followed by early postoperative weight bearing. Cutting-out of
      the lag screw from the femoral head occurred in six fractures and were analysed
      radiographically with regard to fracture type (Evans' classification),
      osteoporosis (Singh grade), accuracy of post-operative reduction (neck-shaft
      angle and diastasis of the fracture), and location of the lag screw in the
      femoral head (depth, height, and antero-postero-posterior radiograph and large
      antero-posterior deviation of the lag screw were significantly related to the
      increased incidence of the screw cutting-out. This suggests that deep insertion
      of the lag screw on the antero-posterior view with central placement on the
      lateral view is an optimal location in the femoral head. The ?cut-out index' (the
      multiplication value of the depth and the anteroposterior deviation of the lag
      screw in the femoral head) is an excellent measure of the risk of the lag screw
      cutting-out.

PMID- 9659483
TI  - Disability after severe injury: five year follow up of a large cohort.
AB  - The early outcome for severely injured patients has improved in the last 20
      years, but the level of continuing long term disability in such patients is not
      known. A large cohort of severely injured patients (ISS > 15) were interviewed
      and examined approximately 5 years following their injury. We present the
      preliminary results which show that only 30 per cent had made a full recovery,
      and that an alarming 47 per cent remain with moderate, severe or very severe
      disabilities. A large proportion (45%) of the persisting disability is due to
      pelvic and limb injury (74 per cent if brain and spinal cord injuries are
      excluded). This study reflects initial treatment in 13 District General Hospitals
      and one Teaching Hospital in a single geographical region in 1989 and 1990, and
      is the first such study in the UK. We conjecture whether more aggressive and
      specialized treatment and rehabilitation, especially of orthopaedic injuries,
      would improve these disappointing results.

PMID- 9659484
TI  - The role of MRI in the diagnosis of occult hip fractures.
AB  - Undisplaced fractures of the hip can occasionally be difficult to diagnose on
      radiographs. We performed MRI scans on 33 patients who had post-traumatic painful
      hips but negative radiographs. Forty per cent of the patients had sustained a
      fractured neck of femur, 15 per cent had sustained an intertrochanteric fracture
      and 11 per cent had sustained other fractures around the hip; in one patient a
      tumour was demonstrated. No fracture was seen in 30 per cent of the patients
      scanned. MRI is well tolerated by elderly patients in pain, does not involve
      ionising radiation and provides early and accurate diagnosis in patients with X
      ray negative post-traumatic hip pain.

PMID- 9659485
TI  - Survey of abdominal ultrasound and diagnostic peritoneal lavage for suspected
      intra-abdominal injury following blunt trauma.
AB  - Over a 3 year period all severely injured blunt trauma patients who were
      investigated with abdominal ultrasound examinations (AUS) or diagnostic
      peritoneal lavage (DPL) to exclude intra-abdominal injury were evaluated. The
      ultrasound examinations were performed by radiologists in 220 severely injured
      patients (20 of whom also had DPL). The overall sensitivity and specificity of
      abdominal ultrasound were 82.7% and 99.5%, respectively. The sensitivity
      increased to 89.1% by repeat scanning. In comparison, 72 DPLs were performed in
      severely injured patients; the overall sensitivity and specificity of DPL were
      82.8% and 97.2%, respectively. DPL resulted in more non-therapeutic laparotomies,
      9/25 (36%) compared with 3/23 (13%) with AUS. Abdominal ultrasound is now the
      first line investigation at this centre for evaluation of possible intra
      abdominal injury in injured patients.

PMID- 9659486
TI  - Tibial plateau fracture following allograft anterior cruciate ligament (ACL)
      reconstruction.

PMID- 9659487
TI  - Femoral neck fracture complicating a missed acetabular fracture in an elderly
      patient.
AB  - We report a case of an elderly patient in whom an acetabular fracture was missed,
      resulting in the unusual complication of an ipsilateral femoral neck fracture.

PMID- 9659488
TI  - Aneurysm of the thyrocervical trunk after blunt cervical injury.

PMID- 9659489
TI  - Radial stress fracture adjacent to a metal plate following weight training.

PMID- 9659490
TI  - Unreamed intramedullary nailing of femoral shaft fractures using a traction
      device.
AB  - The authors present a simple distraction apparatus that is used in the sterile
      field and makes it possible to perform unreamed intramedullary nailing of the
      femur on a normal operation table. Intramedullary (IM) nails were placed, without
      reaming, in 24 femoral shaft fractures with the use of this device. Although it
      appears as though the use of the distractor did not lengthen the operative
      procedure, the set-up time was 60 per cent less compared with a stratified group
      of 28 femoral nailing using the fracture table. We feel that this device provides
      a safe and effective means for achieving fracture reduction without the need for
      a fracture table. It is especially useful in the multiply injured patient where
      the additional lesions can be treated without the need for patient transfer to
      the fracture table.

PMID- 9659491
TI  - Linkage analysis and the tracking of susceptibility genes.

PMID- 9659492
TI  - Nothing new under the sun: the management of epistaxis.
AB  - The management of epistaxis is reviewed from ancient times onwards. Many curious
      methods have been employed and indeed epistaxis has been encouraged at times.
      Although current management is based on sound principles folklore remedies still
      predominate amongst some of our patients. The basis of contemporary treatments
      was known and practised by our ancient forbears.

PMID- 9659493
TI  - Hypersensitive allergic reactions to bismuth-iodoform-paraffin paste following
      ear surgery.
AB  - The case notes of 185 patients who had bismuth-iodoform-paraffin paste (BIPP)
      impregnated ribbon gauze used for packing following ear surgery were analysed
      retrospectively. The incidence of hypersensitive allergic reactions to BIPP was
      5.9 per cent and a five-fold increase risk of developing allergic reactions was
      found in those with previous exposure to BIPP. Where temporalis fascia was used
      to repair tympanic membrane defects, the incidence of tympanic membrane graft
      perforations was higher when allergic reactions to BIPP developed post
      operatively, compared to non-allergic cases.

PMID- 9659494
TI  - Surgical removal of 11 cochlear implants--lessons from the 11-year-old Cambridge
      programme.
AB  - This is a retrospective study of 10 patients (11 ears) out of 132 cochlear
      implant patients of the Cambridge cochlear implant programme. These patients have
      all been explanted. Individual problems have been studied, relevant literature
      reviewed and the pitfalls of implant surgery re-examined in the light of our
      experience.

PMID- 9659495
TI  - Epidural application of ionomeric cement implants. Experimental and clinical
      results.
AB  - During setting and hardening, the hybrid bone substitute ionomeric cement
      (Ionocem) achieves a stable and durable bond with the apatite of the adjacent
      bone without interpository soft tissue. Fluid contact during setting results in
      the release of aluminium ions which may reach critical levels as high as 3000
      micrograms/l. On epidural application it is, therefore, essential to prevent
      cement constituents from gaining access to the intradural space. After the cement
      has hardened, the presence of aluminium is demonstrable in the adjacent bone to a
      maximum depth of 20 microns (EDX microanalysis). In rabbits, epidural placement
      of freshly mixed cement causes slight thickening of the dura. There is reason to
      believe that human dura, with a thickness 10 times greater, is impermeable to
      components of the cement. After epidural application of the freshly mixed cement
      in the frontobasal and laterobasal regions and at the skull cap and petrous apex,
      76 patients in all have been followed for up to 6.5 years. During this period no
      complications have arisen and functional (and cosmetic) results are promising.
      The availability of preformed implants (Ionoroc, Ionocast) permitted the
      peridural placement of minimal quantities of freshly mixed cement. These implants
      were fixed to localized sites on the adjacent calvarial bone by use of Ionocem.
      Notwithstanding the stringent manufacturer guidelines, there have been reports in
      the literature that during the vulnerable stage of setting neurotoxic aluminium
      ions were released into the dural space with a fatal outcome in two cases. In
      view of potential intradural complications, such as may occur in case of dural
      leaks, it was considered that further application of the material adjacent to the
      dura was no longer warranted. The production of Ionocem was discontinued in May
      1995.

PMID- 9659496
TI  - A prospective evaluation of the feasibility of day-case microlaryngeal surgery.
AB  - An increasing number of surgical procedures are being performed on a day-case
      basis. In the UK otolaryngologists have been reluctant to introduce same day
      discharge in microlaryngeal surgery (MLS). The reason for this is the perceived
      risk to the airway from bleeding and oedema after MLS. The aim of this study was
      to investigate the feasibility of establishing a same day discharge service for
      MLS patients. One hundred consecutive patients under the care of one consultant
      otolaryngologist were recruited. A clinical street-fit assessment and objective
      measures of peak expiratory flow rate (PEFR) and oxygen saturation (SaO2) were
      recorded pre- and post-operatively. Results indicate that the PEFR and SaO2 did
      not change significantly during the course of the study. The street-fit criteria
      for discharge were satisfied in 80 per cent of patients following surgery. By
      combining the ASA score (American Society of Anaesthesiologists) with street
      fitness 63 per cent of our patients were eligible for same day discharge.

PMID- 9659497
TI  - Pull-through oropharyngectomy in advanced stage malignant tumours.
AB  - Surgery is the first therapeutic option in extensive oropharyngeal carcinomas. An
      operation to treat these tumours is described, based on the hemiglossopelvectomy
      without mandibulectomy technique. Tumours located in the oropharynx are resected
      downwards by a modified pull-through approach, performing the resection of the
      oropharyngeal tumour in monoblock with the ipsilateral neck dissection, avoiding
      any action upon the mandible. The operation has been performed in 14 consecutive
      patients. By avoiding either mandibulotomy or mandibulectomy, morbidity and post
      operative recovery are improved.

PMID- 9659498
TI  - The usefulness of computed tomography in the diagnosis of impacted fish bones in
      the oesophagus.
AB  - The usefulness of computed tomography (CT) in the diagnosis of fish bone
      impaction in the oesophagus was evaluated. Thirty-two patients were examined by
      plain X-ray followed by direct oesophagoscopy for suspected fish bone impaction.
      Among 25 cases in which fish bones were actually removed, foreign bodies were not
      clearly demonstrated by plain X-ray in 14 cases (56 per cent). Eleven cases
      underwent CT prior to the oesophagoscopic examination. Fish bones were clearly
      demonstrated by CT in all patients. CT also clearly visualized secondarily
      induced inflammatory changes in the neighbouring structures. In order to confirm
      this result, we made a simulation model of oesophageal fish bone impaction, using
      fish bones of three different species surrounded by a water bag. In comparison
      with plain X-ray, CT depicted a superior image of fine fish bones and provides
      extremely useful information for the management of impacted fish bones in the
      oesophagus.

PMID- 9659499
TI  - Bilateral conductive deafness related to erosive lichen planus.
AB  - A case of bilateral progressive stenosis of both external auditory canals with
      resultant conductive hearing loss is presented. The stenosis revealed multifocal
      erosive and synechiant lichen planus. To our knowledge, this is the first
      reported case of lichen planus involvement of the external ear.

PMID- 9659500
TI  - Successful treatment of rhinocerebral mucormycosis by a combination of aggressive
      surgical debridement and the use of systemic liposomal amphotericin B and local
      therapy with nebulized amphotericin--a case report.
AB  - A case of mucormycosis involving the nose and paranasal sinuses in a 55-year-old
      man with recently diagnosed acute promyelocytic leukaemia is reported. It was
      successfully treated with a combination of aggressive surgical debridement and
      systemic amphotericin B. In addition, local nebulized amphotericin B was used as
      an adjunct to therapy. We believe this is only the second documented use of
      nebulized amphotericin in the management of sinonasal mucormycosis. The need for
      a high index of suspicion and early aggressive management is emphasized.

PMID- 9659501
TI  - Craniofacial necrotizing fasciitis secondary to sinusitis.
AB  - Necrotizing fasciitis is a rare condition which usually affects the trunk,
      perineum and limbs. Head and neck involvement is very uncommon and in most cases
      it is secondary to orbital or dental infection. We report a case of craniofacial
      necrotizing fasciitis (CNF) secondary to a maxillary sinusitis. The patient was
      treated intensively with antibiotics, surgical procedures and life-support
      measures. Despite all efforts, the patient died one week after admission. This
      case highlights early diagnosis and aggressive management as decisive factors for
      the outcome of the patient.

PMID- 9659502
TI  - Granular cell tumour of the larynx.
AB  - Granular cell tumour (GCT) is a benign tumour with abundant eosinophilic
      cytoplasm filled with granules of varying sizes. These granules are the defining
      characteristic of the GCT and are believed to represent lysosomes in varying
      stages of fragmentation. The commonly used term granular cell myoblastoma, found
      in the older literature, is a misnomer because the tumour is clearly not of
      muscle origin. Among the major theories of origin, some support the tumour's
      derivation from neuronal tissue, histiocytes, fibroblast or Schwann cells. In the
      larynx, pseudoepitheliomatous hyperplasia may predispose to confuse the GCT with
      squamous cell carcinoma. The most common region of GCT is in the head and neck,
      accounting for approximately 30 to 50 per cent of all lesions. The larynx is
      relatively an uncommon location for these tumours, accounting for approximately
      three to 10 per cent of the reported cases. Affected patients typically present
      with persistent hoarseness, stridor, haemoptysis, dysphagia, and otalgia, but the
      tumour may be asymptomatic and be discovered only incidentally during a routine
      examination. Complete excision with an attempt to maintain normal structures
      generally results in cure. We present the case of a patient with typical features
      of a GCT of the larynx. The gross appearance, histopathology and brief discussion
      of the current literature are also presented.

PMID- 9659503
TI  - Ortner's syndrome revisited.
AB  - Hoarseness of voice due to paralysis of the left recurrent laryngeal nerve caused
      by a dilated left atrium in mitral stenosis as discussed by Ortner, is a subject
      of controversy. Different authors have cited different mechanisms as explanation.
      A variety of cardiac problems such as primary pulmonary hypertension, ischaemic
      heart disease, various congenital heart disorders can all lead to paralysis of
      the left recurrent laryngeal nerve. Most authors believe that pressure in the
      pulmonary artery causes the nerve compression. In Papua New Guinea cor pulmonale
      and rheumatic heart disease are the commonest cardiac disorders seen. Ortner's
      syndrome is a rarity and has never been reported from here before. Here three
      different case reports are presented with mitral stenosis, primary pulmonary
      hypertension and combined mitral stenosis and regurgitation and the pathogenesis
      of hoarseness is discussed.

PMID- 9659504
TI  - Failure to control the airway in a patient with Hunter's syndrome.
AB  - Hunter's syndrome is due to recessively inherited mucopolysaccharide storage
      diseases. The anaesthetic complications in this syndrome are related to the
      organs involved in the disease, but pertain especially to upper airway
      obstruction problems. We report a patient with Hunter's syndrome who, while under
      general anaesthesia for a simple procedure (the introduction of bilateral
      grommets), suffered a fatal outcome.

PMID- 9659505
TI  - Internal jugular vein thrombosis in association with the factor V Leiden
      mutation.
AB  - We report an unusual case of internal jugular vein thrombosis in a 57-year-old
      female, with the recently discovered factor V Leiden (FVR506Q) mutation. The
      molecular basis of this mutation is described, and the importance of screening
      for hereditary venous thrombotic states is emphasized.

PMID- 9659506
TI  - The case of the missing carotid artery--a well aimed knife!
AB  - A 20-year-old male presented with a small stab wound to the neck and with
      haemodynamic signs of significant haemorrhage, but no signs of local bleeding. On
      exploration, an intact vagus nerve and internal jugular vein were found, but the
      common carotid artery was not immediately apparent. Careful dissection confirmed
      a completely transected common carotid artery with the two ends contracted and
      retracted. A primary repair was performed and post-operatively the patient
      recovered completely and had no neurological deficit.

PMID- 9659507
TI  - Oncogenic osteomalacia: case report and review of head and neck associated
      tumours.
AB  - Oncogenic osteomalacia is an uncommon syndrome characterized by mineral
      metabolism abnormalities that disappear after the resection of an associated
      tumour. Head and neck is the second most frequent location of these tumours. We
      describe a case with an ethmoido-frontal phosphaturic mesenchymal tumour and
      review oncogenic osteomalacia-associated tumours. Among 21 cases found, 57 per
      cent affected the sinonasal area and 20 per cent the mandible. The diagnosis of
      the tumour lasted a mean of 4.7 years from the onset of osteomalacia, and most of
      them showed a significant vascular component. An aggressive surgical approach is
      recommended.

PMID- 9659508
TI  - Dual ectopic thyroid: a report of two cases.
AB  - Ectopic thyroid is an uncommon embryological aberration characterized by the
      presence of thyroid tissue at a site other than in its usual pretracheal region.
      Usually it occurs along the path of descent of the developing thyroid primodium
      from the foramen caecum, commonest being lingual followed by sublingual and in
      the anterior midline of neck at, or below, the level of the hyoid bone. It is
      unusual for lingual thyroid to present simultaneously with another ectopic
      thyroid; reported here are two such cases.

PMID- 9659509
TI  - Delayed massive epistaxis due to traumatic intracavernous carotid artery
      pseudoaneurysm.
AB  - Recurrent epistaxes after head injury may rarely be due to a traumatic
      intracavernous carotid artery pseudoaneurysm. The head injury is usually
      associated with fracture of the skull base and the epistaxes are severe with the
      first episode generally occurring one to three months after the initial trauma.
      We present a case which illustrates the role of high resolution computed
      tomography (CT) scanning and also magnetic resonance angiography (MRA) in
      achieving the diagnosis.

PMID- 9659510
TI  - Verrucous carcinoma of the maxillary antrum.
AB  - Verrucous carcinoma is a distinct variant of well differentiated squamous cell
      carcinoma. Its occurrence in the maxillary antrum is rare. Only three cases have
      previously been documented. We present a case report of verrucous carcinoma in
      the maxillary antrum and a review of the literature.

PMID- 9659511
TI  - Primary ethmoid sinus craniopharyngioma: a case report.
AB  - A seven-year-old boy complained of intermittent epistaxis for several months.
      Computerized tomography (CT) scans showed increased soft tissue density over the
      left ethmoid sinus. Endoscopic sinus surgery was used to remove the mass
      completely. The pathological report was craniopharyngioma. No other focus of
      lesion was found, and he continues to do well.

PMID- 9659512
TI  - Four cases of aggressive MRSA wound infection following head and neck surgery.

PMID- 9659513
TI  - Cancer screening in otorhinolaryngology.

PMID- 9659514
TI  - Human herpes virus 8 (Kaposi's sarcoma herpesvirus).
AB  - Human herpes virus 8 (HHV-8) is a recently discovered herpesvirus related to
      Herpesvirus saimiri and Epstein-Barr virus (EBV). It has been assigned to the
      Rhadinovirus genus (gamma-2 herpesvirus) on the basis of its genomic sequence and
      structure. HHV-8 is the first member of this genus known to infect humans and it
      is now evident that it is the likely cause of Kaposi's sarcoma (KS). The virus is
      present in endothelial and spindle cells of KS, and in HIV disease the presence
      of HHV-8 in peripheral blood, and/or serum IgG antibodies to HHV-8, predicts the
      development of AIDS-related KS. HHV-8 can also infect CD19 + B cells and is of
      aetiological significance in the development of body cavity B cell lymphomas of
      AIDS. Of note, the translation products of viral open reading frames (ORFs)
      reveal HHV-8 to be a molecular pirate, capable of producing homologues of several
      human gene products that may result in alterations in cell cycle arrest, inhibit
      apoptosis and cell-mediated immune responses, and thus provide the potential for
      tumour production.

PMID- 9659515
TI  - Burkitt's lymphoma.

PMID- 9659516
TI  - Mechanisms of cancer inhibition by anti-oxidant nutrients.
AB  - The cancer inhibitory properties of anti-oxidant micronutrients have been well
      established in experimental animal models and cell culture studies. Human studies
      have also tended to indicate an inhibition of various forms of cancer and the
      regression of some precancerous lesions. The biological mechanisms for cancer
      inhibition and regression are now gradually becoming understood, and the anti
      oxidant nutrients appear to act through a number of pathways common to most of
      the agents studied. These various micronutrients appear to act through a complex
      group of "common pathways" of anticancer activity based upon three major
      mechanisms: (1) tumour inhibition by immune cytokines; (2) stimulation of cancer
      suppressor genes, such as "wild type" p53, and diminished expression or
      dysregulation of oncogenes such as mutant p53 and H-ras; (3) inhibition of tumour
      angiogenesis through the inhibition of angiogenesis-stimulating factors such as
      TGF alpha. Retinoid action differs, in some respects, from other micronutrient
      anticancer mechanisms and appears to relate to its stimulation of cellular
      differentiation and resultant apoptosis of neoplastic cells. Combinations of anti
      oxidant nutrients have been shown to be synergistic in their anticancer activity,
      probably due to their optimal anticancer activity at different oxygen potentials.
      Selectivity in the action on cancer cells, as opposed to normal cells, is a major
      feature of the anti-oxidant micronutrients.

PMID- 9659517
TI  - Isolation and characterisation of radioresistant human KB carcinoma cells in
      vitro.
AB  - In order to investigate the radioresistance mechanism in human carcinoma cells,
      we isolated the radioresistant cells from a human KB carcinoma cell line by
      various methods. Although the radioresistant cells were not isolated by the
      repeated X-irradiation method, pretreatment of the cells with mutagens including
      N-methyl-N'nitro-N-nitrosoguanidine and 4-nitroquinoline 1-oxide induced
      radioresistance of 1.50 to 3.75-fold, as judged by the D0 ratio to parental KB
      cells. When three representative radioresistant cell clones with stable growth
      isolated by a different method were examined for cross-resistance to anticancer
      drugs, each cell clone exhibited resistance to one, five and two anticancer
      drugs, including mitomycin C, bleomycin and methotrexate, respectively. Among
      them, the cell line N10, showing stable plating efficiency and population
      doubling time, was further characterised. Consequently, immunocytochemistry,
      Western blotting and flow cytometry revealed that N10 expressed a higher level of
      mutant p53 protein than did parental KB, suggesting the involvement of mutant p53
      protein in radioresistance of N10.

PMID- 9659518
TI  - Mucositis as a biological process: a new hypothesis for the development of
      chemotherapy-induced stomatotoxicity.
AB  - Mucositis induced by antineoplastic drugs is an important, dose-limiting and
      costly side effect of cancer therapy. The ulcerative lesions which result are
      frequent systemic portals of entry for microorganisms which inhabit the mouth and
      consequently are often sources of systemic infection in the myelosuppressed
      patient. A number of clinical observations and the inconsistency of responses to
      a broad range of treatment modalities suggests a physiological complexity to
      mucositis which has not previously been comprehensively considered. We now
      propose a hypothesis as to the mechanism by which mucositis develops and
      resolves, which is based on four phases: an initial inflammatory/vascular phase;
      an epithelial phase; an ulcerative/bacteriological phase; and a healing phase.
      The role of cytokines as initiators and ampliers of the process is discussed, as
      is the potential influence of genetic factors in establishing risk and modifying
      the course of stomatotoxicity.

PMID- 9659519
TI  - Salivary gland carcinomas: prognostic significance of simple mucin-type
      carbohydrate antigens.
AB  - The prognosis of salivary gland carcinomas is difficult to assess. Simple mucin
      type carbohydrates (T and sialosyl-T antigens, Tn and sialosyl-Tn antigens) have
      been shown to be of value in predicting prognosis for carcinomas in other
      locations. We studied the prognostic significance of the expression of these
      structures in a retrospective study of 133 patients with salivary gland
      carcinomas, using immunohistochemistry and a panel of well-defined monoclonal
      antibodies (MAbs) on formalin-fixed paraffin-embedded tissues. Sialosyl-Tn, T and
      sialosyl-T antigens were not correlated with prognosis. Univariate analyses
      showed no overall difference in survival or locoregional control between patients
      with Tn-positive and patients with Tn-negative tumours, but indicated that
      expression of the Tn antigen was associated with early locoregional recurrences
      and deaths. Tn was, however, not an independent prognostic factor by multivariate
      regression analysis.

PMID- 9659520
TI  - Cellular factors may enable squamous carcinoma cells to overcome TGF beta
      mediated repression of CDK2 activity.
AB  - Cell lines developed from head and neck squamous cell carcinomas exhibit variable
      responses to the negative regulatory effects of transforming growth factor beta
      (TGF beta) on cell growth. To analyse the effects of TGF beta on regulators of
      cell cycle progression, we characterised cell lines derived from head and neck
      squamous cell carcinoma (HNSCC) for their biological sensitivities to TGF beta,
      growth inhibition, then examined the effects of TGF beta treatment on the
      expression and activity of cyclin dependent kinases (CDKs) and inhibitors of
      these kinases. Western blot analysis of cell lysates from untreated or TGF beta
      treated cultures showed no alterations in expression of CDK2, CDK4, CDK6 or
      cyclin E in cell lines which were either sensitive (HaCaT, HN6) or refractory
      (HN12, HN30) to the growth-inhibitory effects of TGF beta. However, treatment of
      cells with TGF beta resulted in a several fold increase in cellular levels of p21
      (WAF1/Cip1), irrespective of biological response. Immune complex in vitro kinase
      assays demonstrated that the activity of CDK2 was inhibited by exposure to ligand
      in each case, confirming that a TGF beta signalling pathway which regulates
      kinase activity was intact in these cell lines. The data suggest that cellular
      factors expressed in HN12 and HN30 enable these cells to override TGF beta
      mediated inhibition of CDK2 activity and allow cell cycle progression. This may
      represent an important mechanism which allows cells to evade growth arrest during
      malignant progression.

PMID- 9659521
TI  - Immunohistochemical localization of a urokinase-type plasminogen activator system
      in squamous cell carcinoma of the oral cavity: association with mode of invasion
      and lymph node metastasis.
AB  - The binding of urokinase-type plasminogen activator (uPA) to its receptor (uPAR)
      has been implicated in cancer invasion and metastasis. This activity is known to
      be regulated by several inhibitors such as plasminogen activator inhibitors
      (PAIs). To elucidate the participation of the uPA system in the malignant
      behaviour of squamous cell carcinoma (SCC) in the oral cavity, uPA, uPAR, PAI-1
      and -2 expression and localisation in 34 primary oral cancers were examined
      immunohistochemically. The results were then compared with clinicopathological
      findings. The positive rates of uPA, uPAR, PAI-1 and -2 expression were 23.5,
      29.4, 29.4 and 11.8%, respectively. uPA expression correlated with mode of cancer
      invasion according to Yamamoto-Kohama's criteria (p < 0.01) and with secondary
      regional lymph node metastasis. uPAR expression also correlated with mode of
      invasion. In particular, the tumours of both uPA- and uPAR-positive
      [uPA(+)/uPAR(+)] cases were highly invasive. In the present study, neither PAI-1
      nor PAI-2 expression correlated with clinicopathological parameters. However, PAI
      2 negative cases of uPA(+)/uPAR(+) were significantly more invasive (p < 0.0001).
      Such uPA(+)/uPAR(+)/PAI-2(-) cases almost always showed secondary lymph node
      metastasis (p < 0.01). These results indicate that the uPA system plays a
      significant role in the invasive and metastatic processes of oral SCC, and that
      this system may be a powerful aid in evaluating the clinical course or prognosis
      of patients with oral cancer.

PMID- 9659522
TI  - Scoring oral mucositis.
AB  - Oral mucositis is a common, dose limiting and potentially serious complication of
      both radiation and chemotherapy. Both these therapies are non-specific,
      interfering with the cellular homeostasis of both malignant and normal host
      cells. An important effect is the loss of the rapidly proliferating epithelial
      cells in the oral cavity, gut and in the bone marrow. Within the mouth, the loss
      of these cells leads to mucosal atrophy, necrosis and ulceration. Although post
      treatment healing is generally uneventful, severe mucositis can be life
      threatening, especially if complicated by dehydration or secondary infection.
      Accurate and reproducible evaluation of oral mucositis is important in order to
      monitor patient toxicity during therapy, to document the toxicity of conventional
      therapy and to critically assess the effects of alternative therapies. A number
      of oral toxicity scoring systems have been described, but direct comparisons have
      rarely been undertaken and little data exist regarding inter- and intra-user
      reliability. This paper reviews a number of oral mucositis scoring systems that
      are commonly used and will also discuss, briefly, the biological basis of its
      development and management.

PMID- 9659523
TI  - Absorbed doses in the head and oral cavity during total body irradiation.
AB  - Conditioning before bone marrow transplantation (BMT) with total body irradiation
      (TBI) and cyclophosphamide carries the risk of severe long-term complications.
      The aim of the present study was to determine absorbed doses in the craniofacial
      area during TBI, using thermoluminescent dosimeters for both in vivo techniques
      and phantom measurements. The results from the phantom study showed that the mean
      deviation from the reference dose varied between -5.1 and +11.1%. The superficial
      part of left parotid gland received 11.1 +/- 1.5% more radiation compared with
      the reference. In patients, deviations from the reference dose varied in
      individual patients between -22.4 and +20.1% in various intra-oral sites. Since a
      small increase in dose can result in a significantly increased risk of pathology,
      the observed dose inhomogeneities for structures receiving tangentially directed
      radiation therapy, such as the parotid glands, may contribute to salivary
      dysfunction after TBI.

PMID- 9659524
TI  - Atypical mitoses in lesions of the oral mucosa: a new interpretation of their
      impact upon tumorigenesis.

PMID- 9659525
TI  - Characterization of N-acetylcysteine and ambroxol in anti-oxidant therapy.
AB  - Reactive free oxygen radicals are known to play an important role in the
      pathogenesis of various lung diseases such as idiopathic pulmonary fibrosis
      (IPF), adult respiratory distress syndrome (ARDS) or cystic fibrosis (CF). They
      can originate from endogenous processes or can be part of exogenous exposures
      (e.g. ozone, cigarette smoke, asbestos fibres). Consequently, therapeutic
      enhancement of anti-oxidant defence mechanisms in these lung disorders seems a
      rational approach. In this regard, N-acetyl-L-cysteine (NAC) and ambroxol have
      both been frequently investigated. Because of its SH group, NAC scavenges H2O2
      (hydrogen peroxide), .OH (hydroxol radical), and HOCl (hypochlorous acid).
      Furthermore, NAC can easily be deacetylated to cysteine, an important precursor
      of cellular glutathione synthesis, and thus stimulate the cellular glutathione
      system. This is most evident in pulmonary diseases characterized by low
      glutathione levels and high oxidant production by inflammatory cells (e.g. in IPF
      and ARDS). NAC is an effective drug in the treatment of paracetamol intoxication
      and may even be protective against side-effects of mutagenic agents. In addition
      NAC reduces cellular production of pro-inflammatory mediators (e.g. TNF-alpha, IL
      1). Also, ambroxol [trans-4-(2-amino-3,5-dibromobenzylamino)-cyclohexane
      hydrochloride] scavenges oxidants (e.g. .OH, HOCl). Moreover, ambroxol reduces
      bronchial hyperreactivity, and it is known to stimulate cellular surfactant
      production. In addition, ambroxol has anti-inflammatory properties owing to its
      inhibitory effect on the production of cellular cytokines and arachidonic acid
      metabolites. For both substances effective anti-oxidant and anti-inflammatory
      function has been validated when used in micromolar concentrations. These levels
      are attainable in vivo in humans. This paper gives an up-to-date overview about
      the current knowledge of the hypothesis that oxidant-induced cellular damage
      underlies the pathogenesis of many human pulmonary diseases, and it discusses the
      feasibility of anti-oxidant augmentation therapy to the lung by using NAC or
      ambroxol.

PMID- 9659526
TI  - The use of home nebulizers in adult asthma.
AB  - Nebulization therapy is an approach for the treatment of respiratory diseases
      such as asthma which was not anticipated in the international recommendations for
      the treatment of asthma and which merits study. Even if the place of nebulizers
      in the treatment of asthma exacerbations has been validated, this is not the case
      for adult asthmatic subjects with chronic asthma. While asthma control for most
      patients can be achieved using metered-dose inhaler and dry powder inhaler
      therapy, some patients may require regular home nebulized therapy. Before
      determining the objectives and therapeutic characteristics of nebulization in the
      treatment of chronic asthma in the adult patient, we shall first describe the
      pathophysiological elements involved in the treatment of asthma and of the couple
      'nebulized substance-nebulizer' leading to an optimal nebulization.

PMID- 9659527
TI  - The measurement of the single-breath transfer factor for carbon monoxide and its
      components using the Morgan Transflow system.
AB  - In contrast to the standard single-breath transfer factor for carbon monoxide
      (TLCO), there are no specific guidelines or recommendations for the measurement
      of its components, the pulmonary capillary blood volume (VC) and membrane
      component (DM), by the Roughton and Forster method. Ten randomly selected heart
      transplant patients (three life-long non-smokers, seven ex-smokers > 1 yr, age
      range 24-55 years) were assessed on two occasions using either the standard or
      high-oxygen mixture as the first inspired gas in random order. Ten normal
      subjects (all non-smokers, age range 23-54 years) were assessed on two occasions
      using either a long protocol (30 min waiting time between repeat measurements in
      an individual set) or a short protocol (5 min waiting time). Two technically
      acceptable results of TLCO were used to derive a mean value for DM and VC for
      each set of measurements (Transflow, P. K. Morgan, Kent, U.K.). The different
      sequences of gas mixtures produced no significant differences between the values
      obtained in ten heart transplant patients for mean TLCO (mmol min-1 kPa-1)
      (standard first 5.13 +/- 1.15, high-oxygen first 5.14 +/- 1.12; limits of
      agreement -0.57 to 0.59 for DM or for VC. The long or short protocol produced no
      significant differences between the means of TLCO (mmol min-1 kPa-1) (long 8.0 +/
      1.9, short 8.0 +/- 1.9; limits of agreement -0.5 to 0.5), DM or VC. This allows
      the development of a standard test protocol of short duration (about 40 min)
      making it practical for clinical use without compromising the precision or
      reproducibility of the results obtained.

PMID- 9659528
TI  - Curved chest tube for drainage of malignant pleural effusion.
AB  - Thoracentesis with a chest tube insertion and drainage of large pleural effusion
      is widely performed in patients with malignant lung diseases. One potential
      problem with a conventional chest tube placement is occasional incomplete
      evacuation of effusion owing to inappropriate position of the tip where the
      drainage holes opened. We have developed a curved chest tube and evaluated the
      position of tip placement just after the placement and before removal on plain
      chest X-ray in 20 patients with massive pleural effusions due to lung cancer. In
      15 of the 20 patients, the tip of the tube was successfully positioned at the
      paravertebral gutter in posterobasal with higher drainage efficacy compared with
      other patients whose tube tips happened to be positioned at other sites. There
      were no significant complications. This study suggested that the curved chest
      tube would be safe and useful in completing drainage of pleural effusion.

PMID- 9659529
TI  - Prescribing for persistent cough in children.
AB  - To identify the medications general practitioners consider for the treatment of
      persistent isolated cough, we undertook a postal questionnaire survey of a sample
      of general practitioners in east London. Fewer than 10% indicated that they never
      prescribed for such cough. About 70% sometimes considered antibiotics and/or
      bronchodilators in all age groups. Inhaled steroids and cromoglycate were
      considered by about 30% of prescribers for infants compared with over 60% for
      older age groups. As yet there is no evidence that medication is beneficial for
      persistent isolated cough. The role of asthma drugs for children with this
      symptom needs to be evaluated so that we can better identify those who are likely
      to benefit.

PMID- 9659530
TI  - Variations in hospitalization rates for asthma among black and minority ethnic
      communities.
AB  - In response to the introduction of ethnic monitoring within the U.K. hospital
      inpatient data set, this study investigates the variations in secondary
      healthcare utilization by Black and minority ethnic communities whose cause of
      admission is related to asthma. The study examines all residents of the West
      Midlands: over 5 million people, of whom 8.5% are from Black and minority ethnic
      groups. A retrospective study of 15,921 asthma-related hospital admissions, from
      1 April 1995 to 31 March 1996, was carried out. Age-standardized admission rates
      were higher in all Black and minority ethnic groups studied than in the White
      group. There were elevated rates in Black children aged 5-14 years, and
      particular differences were observed for Indian and Bangladeshi men and women
      aged 65 years or over. Emergency admissions to hospital for asthma were strongly
      associated with patients' socioeconomic background but this was largely observed
      for Black and minority ethnic groups that also generally experience high levels
      of deprivation. The findings support previous studies which suggest that hospital
      utilization rates for asthma among people from Black and minority ethnic groups
      are high compared with the White group, despite little evidence in measured
      prevalence. This study suggests that ethnic background is more important in
      asthma admissions than deprivation, which raises serious concerns on the
      appropriateness and quality of asthma care for these patient groups within our
      society. Future studies need to examine pathways to care, that is the health
      seeking behaviour of Black and minority ethnic groups, the type of treatment
      received at the primary care level and referral patterns to secondary care.

PMID- 9659531
TI  - HLA-DQB1 and HLA-DPB1 genotypes in familial sarcoidosis.
AB  - Numerous reports on the familial occurrence of sarcoidosis, on regionally
      different prevalences and on its associations with genetic polymorphisms point to
      the existence of predisposing genes. We have started to establish a collection of
      DNA from families with two or more sarcoidosis patients for the purpose of
      genetic linkage and association studies. In this report we present HLA class II
      genotypes of affected first-degree relatives from 17 families, including eight
      instances of affected parent and offspring, six sib pairs, and three sib
      triplets. Genotyping for HLA-DQB1 revealed an over-representation of DQB1*0603
      and DQB1*0604 among alleles shared by affected first degree relatives. The same
      was found for HLA-DPB1*0201 (Glu69 positive). However, none of the sib triplets
      had any of these alleles in common.

PMID- 9659532
TI  - Improved lung function and quality of life following increased elastic recoil
      after lung volume reduction surgery in emphysema.
AB  - Lung volume reduction surgery for severe emphysema with removal of 20-30% of the
      most destroyed parts of the lung parenchyma has been reported to improve lung
      function substantially. Increased elastic recoil has been suggested as one
      underlying mechanism for the improvement. Fourteen patients, seven men and seven
      women with a mean age of 62 years, who underwent bilateral lung volume reduction
      surgery have been followed up for 3 months. We here report the data on quality of
      life, lung function and elastic recoil. FEV1.0 increased by a mean of 26% from
      0.581 to 0.731 (P < 0.01). The mean TLC was reduced by 16% from 8.91 to 7.51 (P <
      0.001). The level of hyperinflation decreased as implied by a reduction in the
      ratio of RV to TLC from 0.70 to 0.60 (P < 0.001). The pulmonary elastic recoil
      improved, with an increase in the transpulmonary pressure at maximal inspiration
      (PelTLC) from 0.95 kPa to 1.35 kPa (P < 0.05) and an average increase in the
      coefficient of retraction PelTLC/TLC) from 0.12 kPa l-1 to 0.19 kPa l-1 (P <
      0.01). The resting PaO2 increased from a mean of 8.7 kPa to 9.8 kPa (P < 0.01).
      The patients reported a high degree of subjective improvement according to the
      St. George's Respiratory Questionnaire and the working capacity on a bicycle
      increased by 26% from a mean of 38 W to 48 W (P < 0.01). The promising short-term
      results of lung volume reduction surgery for severe emphysema appear to be
      related to improved pulmonary elastic recoil.

PMID- 9659533
TI  - Closed percutaneous pleural brushing: a new method for diagnosis of malignant
      pleural effusions.
AB  - Pleural fluid cytology and pleural biopsy are the two most commonly employed
      diagnostic tests for malignant pleural effusions. Here, we have introduced a new
      diagnostic method, namely closed percutaneous pleural brushing, and have compared
      its diagnostic yield with those of pleural fluid cytology and pleural biopsy in
      patients with suspected malignant pleural effusion. Forty-three consecutive
      patients with suspected malignant pleural effusion underwent thoracentesis,
      closed pleural brushing and closed pleural biopsy using Cope's pleural biopsy
      needle and a cytological brush (BC-10C) which was introduced into the pleural
      cavity through the cannula of the same needle. All the samples were sent for
      bacteriological and cytological studies. Patients had a mean follow-up period of
      9.28 +/- 1.87 months during which seven cases whose entire studies were non
      diagnostic underwent thoracotomy and open pleural biopsy. Thirty-four cases were
      finally documented to have malignancy. Closed pleural brushing was positive in 31
      (91%) of cases. This was superior to that achieved by either pleural fluid
      cytology (67%) (P = 0.01) or pleural biopsy (58%) (P = 0.002). No pneumothorax or
      other major complications were encountered with this method. Closed pleural
      brushing via Cope's needle is a relatively safe, simple and well-tolerated
      technique with a high diagnostic yield for patients with malignant pleural
      effusion. It may substitute for other more invasive and more expensive procedures
      such as thoracoscopy and thoracotomy in this group of patients.

PMID- 9659534
TI  - Value of C-reactive protein measurements in exacerbations of chronic obstructive
      pulmonary disease.
AB  - C-reactive protein (CRP) has been shown to be a useful and sensitive indicator of
      pyogenic infections in many clinical situations, including acute pneumonia and
      infective pulmonary exacerbations in cystic fibrosis patients. Exacerbations of
      COPD are often, but not always, associated with demonstrable infection. The value
      of CRP measurement in this situation has not been assessed. We have evaluated CRP
      measurement in 50 patients [age 71 +/- 8 (SD) years] who were admitted to
      hospital with clinical evidence of exacerbation [PaO2 = 7.3 +/- 1.3 (SD) kPa,
      baseline FEV1 = 0.8 +/- 0.4 (SD) l]. These patients all had serial measurement of
      CRP [polarizing immunofluorescence (Abbot, TDx)], peripheral white cell count
      (WCC), body temperature, peak expiratory flow rate, Karnofsky performance status
      and chest X-ray, in addition to serial sputum bacteriological analysis carried
      out in a specialized laboratory. CRP was elevated (> 10 mg l-1) in all patients
      (n = 29) with proven infection [103 +/- 98 (SD) mg l-1]. Levels were markedly
      elevated in patients infected with Streptococcus pneumoniae (mean 156 mg l-1);
      there was also a rapid fall in the CRP with therapy. WCC fell with therapy,
      giving a correlation with CRP level (r = 0.44, P < 0.01). Since CRP elevation was
      observed in patients having exacerbation with proven infections and also in those
      where infection was not proven, it is possible that, while it is a marker for
      COPD exacerbation, it is not necessarily a marker of bacterial infection per se.
      However, it is evident from our study that it is of value in the assessment of
      exacerbations of COPD, where routine bacterial culture of sputum is often
      unreliable, and thus the measurement of serum CRP may provide an additional
      objective indicator of infection.

PMID- 9659535
TI  - The role of self-treatment guidelines in self-management education for adult
      asthmatics.
AB  - Guidelines on asthma management have changed considerably in the last two
      decades. Patient education has gained in popularity and especially asthma self
      management training is thought to be essential in the treatment of adult asthma.
      Since 1989 many researchers have added self-treatment guidelines to self
      management programmes and several studies have found improvements in health
      outcomes, such as lung function, quality of life, use of health care facilities
      and asthma symptoms. However, because of the lack of proper control groups, it is
      not clear whether this has to be attributed to self-treatment guidelines or to,
      for example, more education or more medical attention. The only two studies that
      were placebo controlled did not show an effect of self-treatment. To assess the
      added benefit of self-treatment guidelines to a self-management programme,
      randomized 'placebo' controlled trials of sufficient size with sufficient follow
      up time are necessary. The only difference between intervention and control
      groups should be guidelines for self-treatment.

PMID- 9659536
TI  - Relationship between subjective fatigue and physiological variables in patients
      with chronic obstructive pulmonary disease.
AB  - Patients with chronic illnesses, such as chronic obstructive pulmonary disease
      (COPD), report an increase in the perception of fatigue in the clinical setting.
      Subjective fatigue associated with physiological factors has not been reported.
      The purpose of this study was to determine the relationship between subjective
      fatigue and pulmonary function, respiratory and peripheral muscle force and
      exercise capacity in patients with COPD. Nineteen patients with COPD participated
      in the study [mean (SD) FEV1 38% (17%) predicted]. Fatigue was measured with the
      Multidimensional Fatigue Inventory 20 (MFI-20) that includes the following
      subscale dimensions: general fatigue, physical fatigue, reduced activity, reduced
      motivation, and mental fatigue. The following physical variables were measured:
      forced expiratory volume in 1 s (FEV1), vital capacity (VC), maximal inspiratory
      peak pressure (PImax), symptom-limited bicycle exercise capacity (maximum
      workload) and maximal voluntary isometric muscle force of both left and right
      quadriceps (Qu), hamstrings (Ha), biceps (Bi) and triceps (Tr). The MFI-20
      fatigue dimensions, reduced activity and reduced Motivation, are significantly
      correlated with FEV1 (% predicted) (r = -0.62, r = -0.55 respectively). No
      significant correlation was found between the dimensions of fatigue and maximum
      workload. In contrast the fatigue dimension, physical fatigue, shows significant
      correlations with seven of eight muscle forces measured (Qu left r = -0.49, right
      r = -0.54; Ha left r = -0.49, right r-0.38; Tr left r = -0.61, right r = -0.45;
      Bi left r = -0.46, right r = -0.48). Data from this study show that activity and
      physical dimensions of subjective fatigue are related to pulmonary function and
      skeletal muscle force in COPD patients. Interventions to improve skeletal muscle
      force might improve subjective fatigue in patients with COPD.

PMID- 9659537
TI  - Long-term treatment of asthmatic patients with salmeterol vs slow-release
      theophylline.
AB  - The aim of the present multicentre, open, randomized, parallel group study was to
      evaluate the efficacy and safety of salmeterol versus theophylline in asthmatic
      patients. A total of 112 patients were randomized: 56 received inhaled salmeterol
      (50 micrograms twice daily) and 50 oral dose titrated theophylline twice daily.
      The study lasted 12 months. The efficacy of both drugs was evaluated for the
      first 3 months of the study and the safety for a further 9 months. Spirometric
      measurements were carried out for the total duration of the study. Salmeterol
      showed a greater and more significant efficacy than theophylline in reducing both
      day- and night-time symptoms (P < 0.001) and in reducing additional salbutamol
      requirement (P < 0.001). The subjective assessment of efficacy by physicians and
      patients was in favour of salmeterol from the first month of treatment (P <
      0.001). Both drugs improved the quality of life as measured by the specific
      questionnaire 'Living with Asthma' with no significant differences. The total
      number of adverse events was slightly higher in the theophylline group compared
      with salmeterol (18 vs 9; P n.s.). Both salmeterol and theophylline increased
      morning and evening PEFR with no significant difference. FEV1 and FVC increased
      in both groups of patients; the difference between the effects of the two
      treatment was not statistically significant at 12 months. Our study suggests that
      salmeterol has higher efficacy and safety than theophylline in long-term
      treatment of asthmatic patients.

PMID- 9659538
TI  - Finger clubbing in malignant mesothelioma and benign asbestos pleural disease.

PMID- 9659539
TI  - Pneumonia caused by Pseudomonas putida with a mucoid phenotype.

PMID- 9659540
TI  - Lobectomy in cystic fibrosis.

PMID- 9659541
TI  - Cardiac sarcoidosis: the value of magnetic resonance imaging in diagnosis and
      assessment of response to treatment.

PMID- 9659542
TI  - Detection of Staphylococcus aureus in milk by use of polymerase chain reaction
      analysis.
AB  - OBJECTIVE: To evaluate polymerase chain reaction (PCR) analysis for detection of
      Staphylococcus aureus (nuc gene) in fresh and formalin-preserved milk. SAMPLE
      POPULATION: Samples from 80 lactating sheep and 100 lactating dairy cows.
      PROCEDURE: 4 lactating sheep were inoculated with S aureus by intramammary
      infusion. A set of primers specific for the nuc gene of S aureus was used to
      develop a PCR technique, and modification of the rapid boil method was used to
      isolate bacterial DNA. Milk was obtained from experimentally infected sheep
      before and after infusion with S aureus, and from the 100 cows and remaining 76
      sheep. Samples were screened by bacteriologic culture and PCR. To validate the
      PCR assay, S aureus or other pathogens were added to distilled water and "normal"
      sheep milk samples, with and without formalin. RESULTS: The PCR assay was 100%
      specific for S aureus when known negative and positive samples were tested.
      Sensitivity was 100% for samples with added S aureus or other pathogens.
      Sensitivity was lower for samples obtained from experimentally infected sheep,
      but increased from 53% to 90% with increased washing of target DNA. CONCLUSIONS:
      The PCR technique based on the nuc gene is able to detect S aureus in sheep milk
      yields results faster than does traditional culturing, is highly specific, and is
      able to detect S aureus in formalin-fixed milk samples. CLINICAL RELEVANCE: The
      assay is particularly suitable for analysis of samples shipped or stored without
      refrigeration. Although antibiotics in milk may inhibit growth in culture, they
      should not affect the results of the PCR assay.

PMID- 9659543
TI  - Effect of a competitive inhibitor of platelet aggregation on experimentally
      induced laminitis in ponies.
AB  - OBJECTIVES: To determining whether inhibition of platelet aggregation prevents
      development of carbohydrate overload-induced alimentary laminitis. ANIMALS: 22
      healthy adult ponies. PROCEDURES: Acute laminitis was induced by oral
      administration of corn starch/wood flour to 16 ponies, 8 of which were treated
      with a synthetic analogue of the platelet fibrinogen receptor antagonist peptide
      (RPR) RGDS (arginine-glycine-aspartic acid-serine) 110885; 6 ponies served as
      negative controls. Blood was collected before and at 4, 8, 12, 24, 28, and 32
      hours after administration of carbohydrate overload, and PCV, total plasma
      protein concentration, platelet count, activated clotting time, whole blood
      recalcification time, spontaneous platelet aggregation, ex vivo platelet
      aggregation responses, in vivo platelet activation, and platelet-neutrophil
      aggregates were evaluated. RESULTS: Of 16 ponies given carbohydrate, 6 of 8
      untreated ponies developed laminitis and 0 of 8 ponies treated with RPR 110885
      developed laminitis. The RPR 110885 treatment attenuated the increase in platelet
      neutrophil aggregates observed in untreated ponies. CONCLUSIONS: Platelets are
      involved in the pathogenesis of equine alimentary laminitis. CLINICAL RELEVANCE:
      Platelet aggregation inhibitors may be useful for prevention or treatment of
      laminitis, or both.

PMID- 9659544
TI  - Gelatinolytic activity in tracheal epithelial lining fluid and in blood from
      horses with chronic obstructive pulmonary disease.
AB  - OBJECTIVES: To determine whether gelatinolytic activity in tracheal epithelial
      lining fluid (TELF), blood neutrophils, and blood lymphocytes from horses was
      metalloprotease activity, and to compare, for healthy horses and horses with
      chronic obstructive pulmonary disease, gelatinolytic activity in neutrophils,
      lymphocytes, and serum with activity in TELF. ANIMALS: 7 horses with chronic
      obstructive pulmonary disease (COPD) and 4 healthy control horses. PROCEDURE:
      Neutrophils and lymphocytes were obtained by means of Percoll separation.
      Zymography was used to detect gelatinolytic activity; EDTA inhibition and 4
      aminophenyl mercuric acetate activation were used to verify that gelatinolytic
      activity was metalloprotease activity. RESULTS: Gelatinolytic activity was
      significantly higher in TELF from horses with COPD than in TELF from healthy
      horses. For all samples, EDTA inhibited and APMA activated gelatinolytic
      activity. Gelatinolytic activity of neutrophils, lymphocytes, and serum was not
      significantly different between healthy horses and horses with COPD. CONCLUSIONS:
      Results suggested that gelatinolytic activity in TELF from horses is
      metalloprotease activity. Gelatinolytic activity is increased in TELF from horses
      with COPD, but not in serum, neutrophils, or lymphocytes. Neutrophils and
      lymphocytes are possible sources of gelatinolytic activity in TELF. CLINICAL
      RELEVANCE: Measurements of serum, blood neutrophil, or blood lymphocyte
      gelatinolytic activity were of little value in distinguishing horses with COPD
      from healthy horses.

PMID- 9659545
TI  - Management and environmental risk factors for Salmonella enteritidis
      contamination of eggs.
AB  - OBJECTIVE: To analyze data for 60 poultry flocks voluntarily enrolled in the
      Pennsylvania Salmonella enteritidis Pilot Project and determine management and
      environmental risk factors associated with production of S enteritidis
      contaminated eggs. SAMPLE POPULATION: 60 flocks for which at least 1
      environmental sample (manure or egg-handling equipment) was positive for S
      enteritidis. PROCEDURE: Samples of manure, egg-handling equipment, and mice were
      submitted for bacterial culture of S enteritidis. When S enteritidis was isolated
      from environmental samples, 1,000 eggs were collected from the flock every 2
      weeks for 8 weeks and submitted for bacterial culture. RESULTS: 18 flocks were
      found to have produced contaminated eggs. Estimated overall prevalence of
      contaminated eggs was 2.64/10,000 eggs produced, but flock-specific prevalence
      ranged from 0 to 62.5/10,000 eggs. Flocks with high levels of manure
      contamination were 10 times as likely to produce contaminated eggs as were flocks
      with low levels. However, 5 flocks with low levels of manure contamination
      produced contaminated eggs. CONCLUSIONS: Evaluation of the level of manure
      contamination could be used to help identify flocks at risk of producing S
      enteritidis-contaminated eggs. CLINICAL RELEVANCE: Flocks with high levels of S
      enteritidis-contaminated manure appeared to pose the greatest public health
      threat, and on-farm programs to reduce the prevalence of egg contamination should
      be developed for farms with high levels of manure contamination. Efforts to
      reduce the overall number of on-farm pathogens should decrease the incidence of
      foodborne disease in humans.

PMID- 9659546
TI  - Polymorphism of feline beta-globins studied by reversed-phase high-performance
      liquid chromatography.
AB  - OBJECTIVE: To characterize the feline beta-globin system with respect to the
      number and genetics of adult beta-globin chains. ANIMALS: 84 domestic and
      purebred cats (9 breeds), 14 cats were mildly to severely anemic. For genetic
      analyses, 12 litters with 1 to 5 offspring for a total of 29 kittens. PROCEDURE:
      Feline globins from erythrocyte lysates were separated by reversed-phase high
      performance liquid chromatography and analyzed on the basis of retention time and
      area of each beta-globin peak. Mixing studies with half the amount of hemoglobin
      (Hb) from 2 cats were performed to assign the beta-globin peaks in each cat. The
      Hb from 60 cats were also separated by standard isoelectric focusing methods.
      RESULTS: Heme and alpha- and beta-globins were effectively separated by high
      performance liquid chromatography. Although there was only 1 alpha-globin, a
      total of 6 beta-globins (I through VI) were identified, with each cat having 1 to
      4 beta-globin chains. From analysis of the number of beta-globins, their relative
      amounts, and Hb mixing studies, 17 beta-globin patterns were observed. The beta
      globin pattern in healthy and anemic cats was identical. Family studies
      documented an autosomal codominant mode of inheritance of the adult beta-globins
      and a linkage of 2 beta-chains forming haplotypes. CONCLUSIONS: Biochemical and
      genetic evidence for the greatest polymorphism of adult beta-globins thus far
      described in any species is provided. A feline beta-globin gene region with 2
      linked beta-globin gene loci and 2 and 5 alleles is proposed. CLINICAL RELEVANCE:
      Better understanding of feline Hb will likely be helpful for diagnosis of
      hemoglobinopathies in anemic cats.

PMID- 9659547
TI  - Type-1 hypersensitivity reactions to Malassezia pachydermatis extracts in atopic
      dogs.
AB  - OBJECTIVE: To investigate the potential allergenic role of the yeast Malassezia
      pachydermatis in dogs with clinical diagnosis of atopic dermatitis. ANIMALS: 5
      clinically normal nonatopic dogs, 10 atopic dogs with cytologic evidence of
      Malassezia dermatitis, and 12 atopic dogs without cytologic evidence of
      Malassezia dermatitis. PROCEDURE: A crude yeast extract was produced by
      disrupting the cell wall of M pachydermatis. The crude extract and 8 of its
      fractions, which were generated by fractionation in a high-performance liquid
      chromatography column, were injected along with 46 commercial allergens for
      intradermal allergy testing of normal and atopic sample populations. Significant
      difference between atopic populations was evaluated, using a threshold
      concentration of crude yeast extract that failed to induce wheal-and-flare
      responses in normal nonatopic dogs. RESULTS: Atopic dogs with cytologic evidence
      of Malassezia dermatitis had significantly greater wheal-and-flare reactions to
      intradermal injection of crude extract of M pachydermatis than did atopic dogs
      without cytologic evidence of Malassezia dermatitis. CONCLUSIONS: It is concluded
      that M pachydermatis is capable of promoting type-1 hypersensitivity reactions in
      dogs with an atopic dermatitis phenotype. CLINICAL RELEVANCE: Currently,
      Malassezia dermatitis is principally managed by use of antifungal chemotherapy.
      Because the yeast appears to be a contributing allergen in dogs with atopic
      dermatitis, hyposensitization with M pachydermatis extracts may offer a future
      alternative to extended or repeated episodic administration of antifungals for
      extended control of recurrent infections.

PMID- 9659548
TI  - Interferon-gamma and interleukin 4 gene expression in cows infected with
      Mycobacterium paratuberculosis.
AB  - OBJECTIVE: To determine whether clinical progression of paratuberculosis in
      cattle was associated with alterations in cytokine gene expression in affected
      tissues. ANIMALS: 5 uninfected adult Holstein cows, 7 adult Holstein cows
      naturally infected with Mycobacterium paratuberculosis that did not have clinical
      signs of disease, and 4 adult Holstein cows naturally infected with M
      paratuberculosis that had progressive clinical signs of infection. PROCEDURE:
      Samples of ileum and cecal lymph nodes were obtained from each animal at the time
      of slaughter. A reverse transcriptase-competitive polymerase chain reaction assay
      was used to determine mRNA expression of interferon-gamma (IFN-gamma) and
      interleukin 4 in each sample. RESULTS: Interferon-gamma gene expression was
      significantly higher in ileum and cecal lymph node samples from subclinically
      infected cows than from clinically infected cows. CONCLUSIONS AND CLINICAL
      RELEVANCE: Progression of paratuberculosis to clinical stages is associated with
      reduced expression of IFN-gamma at site of infection. If immune response to M
      paratuberculosis can be manipulated so that IFN-gamma expression is increased,
      resistance to infection in cattle might be enhanced.

PMID- 9659549
TI  - Specificity and duration of neutralizing antibodies induced in healthy cattle
      after administration of a modified-live virus vaccine against bovine viral
      diarrhea.
AB  - OBJECTIVE: To determine the duration for cross-neutralizing antibodies stimulated
      by administration of a single dose of a modified-live vaccine against bovine
      viral diarrhea virus (BVDV) to seronegative cattle. ANIMALS: 23 Angus cows
      seronegative to BVDV. PROCEDURE: Cows were randomly assigned to control
      (unvaccinated) or test (vaccinated) groups. Eighteen BVDV-seronegative Angus
      cattle were vaccinated via IM injection with a modified-live BVDV (NADL strain)
      vaccine and commingled with 5 unvaccinated seronegative cows. Serum was obtained
      from the cows before vaccination, on the day of vaccination, and 1.5, 3, 6, 9,
      12, and 18 months after vaccination. Serum neutralizing antibody tests were
      performed on samples obtained at each point after vaccination, using a panel of
      12 strains of BVDV that, on the basis of reactivity with monoclonal antibodies,
      were identified as heterologous. RESULTS: Antibodies against all 12 strains of
      BVDV (which we tested) were detected by use of viral neutralization testing in
      samples obtained from vaccinated cattle 18 months after vaccination; however,
      concentration of antibody for some of the strains was low. Nonvaccinated cattle
      remained seronegative throughout the 18-month study period. CLINICAL
      IMPLICATIONS: Analysis of these data indicated that modified-live BVDV vaccines
      could stimulate an antibody response in seronegative cows that was detectable for
      at least 18 months after vaccination. These antibodies were able to cross
      neutralize 12 antigenically diverse strains of BVDV.

PMID- 9659550
TI  - Serum-free culture of Pasteurella haemolytica optimized for leukotoxin
      production.
AB  - OBJECTIVE: To screen supernatants of Pasteurella haemolytica cultures grown in 4
      serum-free culture media for maximal leukotoxin (LKT) production and minimal
      protein concentration as an optimal source of LKT for purification. SAMPLE
      POPULATION: One strain of P haemolytica biotype A serotype 1 originally isolated
      from the pneumonic lung of a calf. PROCEDURE: Pasteurella haemolytica was grown
      in brain-heart infusion (BHI) broth, yeast-tryptone broth, RPMI-1640 medium, and
      McCoy's modified 5A medium. Culture biomass and protein concentration, LKT
      activity, and LKT concentration in culture supernatants were measured. Effects of
      media pH and supplementation with metal cations and glucose on growth rate of P
      haemolytica and culture supernatant parameters were evaluated. RESULTS:
      Pasteurella haemolytica cultivated in BHI broth or RPMI-1640 medium containing
      0.1 M phosphate (pH 6.8) produced the highest concentrations of LKT.
      Supplementation of RPMI-1640 medium with 0.36 mM FeCl3 or 1.0 mM MgSO4 further
      increased specific activity of LKT in culture supernatant, but addition of 1%
      glucose did not enhance LKT production. Leukotoxin production in MgSO4
      supplemented RPMI-1640 medium was comparable to that in serum protein
      supplemented medium. CONCLUSIONS: Although BHI broth was superior to RPMI-1640
      medium for P haemolytica growth and LKT production, the higher protein
      concentration and lower LKT specific activity made BHI broth a less desirable
      medium, compared with RPMI-1640 medium. Growth rate and LKT production with
      minimal protein content was optimal in pH 6.8 phosphate-buffered MgSO4
      supplemented RPMI-1640 medium. This medium can serve as a source of culture
      supernatant for purification of LKT.

PMID- 9659551
TI  - Detection of feline herpesvirus 1 DNA in corneas of cats with eosinophilic
      keratitis or corneal sequestration.
AB  - OBJECTIVE: To determine whether feline herpesvirus 1 (FHV-1) DNA is in the
      corneas of clinically normal cats and cats with eosinophilic keratitis or corneal
      sequestration. SAMPLE POPULATION: Corneal biopsy specimens obtained from cats
      referred for treatment of corneal sequestration or eosinophilic keratitis.
      PROCEDURE: Corneal scraping or keratectomy specimens collected from clinically
      normal cats, cats with eosinophilic keratitis, and cats with corneal
      sequestration were evaluated for FHV-1 DNA by use of polymerase chain reaction
      (PCR). DNA was extracted from the tissue, and 1 microgram was assayed for FHV-1
      by use of a single-round (40 cycles) PCR assay with primers directed at a 322-bp
      region of the thymidine kinase gene. Polymerase chain reaction positivity for
      clinically normal and affected cats of various breeds was compared by chi 2
      analysis at alpha = 0.05. RESULTS: The FHV-1 DNA was detected in 5.9% (1/17) of
      corneas from clinically normal cats, in 55.1% (86/156) of corneal sequestra, and
      in 76.3% (45/59) of scraping specimens from cats with eosinophilic keratitis.
      Prevalence was significantly (P < 0.001) greater for cats with corneal
      sequestration or eosinophilic keratitis than for clinically normal cats. For cats
      with corneal sequestration, prevalence of FHV-1 DNA was significantly lower in
      Persian and Himalayan, compared with domestic shorthair and longhair breeds.
      CONCLUSION: Data strongly imply involvement of FHV-1 in the pathogenesis of
      eosinophilic keratitis and corneal sequestration. In Persian and Himalayan
      breeds, however, other nonviral factors also appear to be involved. CLINICAL
      RELEVANCE: Feline herpesvirus 1 must be considered when treating cats with
      corneal sequestration or eosinophilic keratitis.

PMID- 9659552
TI  - Evaluation of the effects of omega-3 fatty acid-containing diets on the
      inflammatory stage of wound healing in dogs.
AB  - OBJECTIVES: To ascertain the effects of dietary omega-3 (n-3) fatty acids on
      biochemical and histopathologic components of the inflammatory stage of wound
      healing. ANIMALS: 30 purpose-bred Beagles. PROCEDURE: Dogs were allotted to 5
      groups of 6. Each group was fed a unique dietary fatty acid ratio of omega-6 to n
      3--diet A, 5.3:1; diet B, 10.4:1; diet C, 24.1:1; diet D, 51.6:1; and diet E,
      95.8:1. Dogs were fed once daily for 12 weeks, then biopsy specimens were taken
      from 4-day-old wounds of each dog and analyzed by gas chromatography-mass
      spectrometry for: prostaglandin E2 (PGE2) metabolites, and ratios of omega-6 to n
      3 fatty acids, arachidonic acid (AA) to eicosapentaenoic acid (EPA), adrenic acid
      to docosahexaenoic acid, and PGE2 to prostaglandin E3 (PGE3) metabolites.
      RESULTS: Qualitative analysis was carried out on AA, EPA, adrenic acid,
      docosahexaenoic acid, and the major metabolite from the PGE2 and PGE3 pathway.
      These molecules were further quantified with respect to diet to determine
      significant differences. By analysis of the AA-to-EPA ratio, diet A was different
      from diets D and E and diets B and C were different from diet E (P < 0.05). By
      analysis of the PGE2-to-PGE3 metabolite ratio, diet A was different from diet E
      (P < 0.05). Though biochemical analysis indicated dietary dependence,
      histopathologic data indicated no significant difference with respect to diet
      groups. CONCLUSION: The biochemical component of the inflammatory stage of wound
      healing can be manipulated by diet. CLINICAL RELEVANCE: Omega-3 fatty acid
      enriched diets can be used to control inflammation associated with dermatologic
      conditions.

PMID- 9659553
TI  - Duration of effects of dietary fish oil supplementation on serum eicosapentaenoic
      acid and docosahexaenoic acid concentrations in dogs.
AB  - OBJECTIVE: To determine how long serum concentrations of omega-3 fatty acids
      remain elevated after cessation of dietary fish oil supplementation. ANIMALS: 12
      healthy Beagles. PROCEDURE: Baseline serum concentrations of linoleic acid,
      linolenic acid, arachidonic acid (AA), eicosapentaenoic acid (EPA), and
      docosahexaenoic acid (DHA) were measured. Dogs were then fed a diet supplemented
      with soybean oil or fish oil for 8 weeks, and serum fatty acid concentrations
      were measured while dogs were fed the experimental diets and for 18 weeks after
      they were switched to a maintenance diet. RESULTS: For dogs fed the fish oil
      diet, serum EPA and DHA concentrations were significantly increased by week 1 and
      remained increased for 7 (DHA concentration) or 3 (EPA concentration) weeks after
      dietary fish oil supplementation was discontinued. CONCLUSIONS: In dogs,
      supplementation of the diet with fish oil may have effects for several weeks
      after dietary supplementation is discontinued. CLINICAL RELEVANCE: Studies of the
      effects of fish oil supplementation that use a crossover design should allow for
      an appropriate washout period.

PMID- 9659554
TI  - Induction of temporary otitis media in specific-pathogen-free pigs by
      intratympanic inoculation of Mycoplasma hyorhinis.
AB  - OBJECTIVE: To examine whether Mycoplasma hyorhinis inoculated into the tympanic
      cavity can cause otitis media in pigs. ANIMALS: 17- or 22-day-old specific
      pathogen-free pigs. PROCEDURE: Histologic and bacteriologic examinations were
      performed on specimens from the tympanic cavity and auditory tube at 0, 7, 14,
      and 25 days after intratympanic inoculation of M hyorhinis (auditory tube cloning
      strain 14). RESULTS: In M hyorhinis-inoculated pigs, mild to moderate
      inflammation of the auditory tube and tympanic cavity first appeared at
      postinoculation day (PID) 7. In pigs euthanatized at PID 14, the degree of
      inflammation was aggravated. Immunohistochemical analysis revealed M hyorhinis
      antigens on the luminal surface of the auditory tube and tympanic cavity. By PID
      25, lesions had lessened. By use of transmission and scanning electron
      microscopic examinations, mycoplasmal organisms were identified among the cilia
      in the auditory tubes at PID 14 but not at PID 25. Results of bacteriologic
      examination indicated that 10(4) to 10(6) color-changing units of M hyorhinis
      were isolated from the tympanic cavity at PID 0. Variable numbers of M hyorhinis
      were isolated at PID 7 and 14, and numbers were decreased at PID 25. CONCLUSIONS:
      M hyorhinis inoculated into the tympanic cavity can cause a self-limiting otitis
      media in SPF pigs.

PMID- 9659555
TI  - Use of peripheral temperature and core-peripheral temperature difference to
      predict cardiac output in dehydrated calves housed in a thermoneutral
      environment.
AB  - OBJECTIVE: To investigate the relation between cardiac output (CO) and peripheral
      (fetlock) temperature (PT) and core-peripheral (rectal-fetlock) temperature
      difference (CPTD) in dehydrated calves housed in a thermoneutral environment.
      ANIMALS: 28 male dairy calves 3 to 10 days old. PROCEDURE: Severe dehydration and
      watery diarrhea were induced by administering diuretics (furosemide,
      hydrohlorothiazide, spironolactone) and sucrose solution. Cardiac output was
      measured by means of thermodilution, core temperature was determined by placing a
      digital thermometer in the rectum, and PT was measured by taping a thermistor to
      the left hind fetlock and insulating the thermistor from ambient air. RESULTS: In
      thermoneutral ambient temperatures (10 to 24 C), PT and CPTD were constant and
      independent of CO at normal or high CO values but were linearly dependent on CO
      below a critical value (78% of normal CO output). Regression equations were
      developed that predicted CO from measured PT or CPTD. At ambient temperatures
      below the lower critical temperature for neonatal calves (8 to 10 C), normal
      values for PT and CPTD in healthy calves were significantly different from those
      at thermoneutral ambient temperatures. CONCLUSIONS AND CLINICAL RELEVANCE:
      Peripheral temperature and CPTD are practical, noninvasive, and inexpensive but
      only moderately useful methods for predicting CO in hemodynamically stable calves
      housed in a thermoneutral environment. Thus, these parameters are of some value
      in daily monitoring of the response to treatment and in determining need for i.v.
      fluid administration in dehydrated calves housed at a dry still-air temperature
      of 10 to 24 C but are of minimal to no value in calves housed at < 10 C.

PMID- 9659556
TI  - Comparison of anion gap and strong ion gap as predictors of unmeasured strong ion
      concentration in plasma and serum from horses.
AB  - OBJECTIVE: To compare the accuracy of anion gap (AG) and strong ion gap (SIG) for
      predicting unmeasured strong ion concentration in plasma and serum from horses.
      ANIMALS: 6 well-trained Standardbred horses undergoing high-intensity exercise
      (experimental study) and 78 horses and ponies that underwent i.v. administration
      of lactic acid or endotoxin, and endurance, submaximal, or high-intensity
      exercise. PROCEDURE: Anion gap was calculated as AG = (Na+ + K+) - (Cl- + HCO3-),
      and SIG was calculated, using the simplified strong ion model, whereby SIG
      (mEq/L) = 2.24 x total protein (g/dl)/(1 + 10(6.65-pH)) - AG. The relation
      between AG or SIG and plasma lactate concentration was evaluated, using linear
      regression analysis. RESULTS: Linear relations between plasma lactate
      concentration and AG and SIG were strong for the experimental study (r2 = 0.960
      and 0.966, respectively) and the published studies (r2 = 0.914 and 0.925,
      respectively). The following relations were derived: AG = 1.00 x plasma lactate +
      10.5; SIG = 0.99 x plasma lactate + 2.8. An AG > 15 mEq/L indicated an increased
      unmeasured anion concentration, whereas a SIG < -2 mEq/L indicated an increased
      unmeasured strong anion concentration. CONCLUSIONS AND CLINICAL RELEVANCE: Anion
      gap and SIG can be used to predict plasma lactate concentration in horses. AG is
      accurate and clinically useful for estimating unmeasured strong ion concentration
      in horses with total protein concentrations within or slightly outside reference
      range, whereas SIG is more accurate in horses with markedly abnormal total
      protein concentrations and those of various ages and with various concentrations
      of albumin, globulin, and phosphate.

PMID- 9659557
TI  - Influence of exogenous hyaluronan on synthesis of hyaluronan and collagenase by
      equine synoviocytes.
AB  - OBJECTIVE: To evaluate the influence of exogenous hyaluronan (HA) on in vitro
      synthesis of HA and collagenase by equine synoviocytes from normal and inflamed
      joints. ANIMALS: 9 adult horses. PROCEDURE: Synoviocytes for culture were taken
      from the middle carpal joint of 3 horses with normal joints (control) and 6
      horses with osteochondral fractures (principal). Synoviocytes were propagated in
      monolayer cultures and were incubated with 3 commercial HA products at
      concentrations of 0, 200, 400, and 1,500 micrograms/ml. Newly synthesized HA was
      radiolabeled with [3H]glucosamine and quantified by cetylpyridinium chloride
      precipitation and liquid scintillation counting. The hydrodynamic size of
      radioactive HA was determined by high-performance liquid chromatography, and
      collagenase activity was evaluated by use of a quantitative radioactive collagen
      film assay. RESULTS: Exogenous HA influenced neither the rate of synthesis nor
      the hydrodynamic size of the newly produced HA by control or principal cell
      cultures. Culture supernatants from abnormal synovium, exposed to 400 and 1,500
      micrograms of exogenous HA/ml, contained significantly more collagenase activity
      than did those exposed to lower concentrations. CONCLUSION: Although HA is
      thought to have beneficial effects in equine arthropathies, the principal
      mechanisms of action of HA do not appear to be stimulation of synthesis of HA of
      augmented molecular weight or marked inhibition of collagenase synthesis.

PMID- 9659558
TI  - Regional distribution of blood flow in the brain of horses at rest and during
      exercise.
AB  - OBJECTIVE: To examine regional distribution of blood flow in the brain of horses
      at rest and during exercise. ANIMALS: 9 clinically normal horses. PROCEDURE:
      Regional brain blood flow was measured using radionuclide-labeled 15-microns
      diameter microspheres injected into the left ventricle, while reference blood
      samples were obtained from the aorta. RESULTS: At rest, cerebral cortex and
      caudate nuclei received significantly higher blood flow, compared with cerebral
      white matter. A similar perfusion heterogeneity existed in the cerebellum. In the
      brain stem, a gradual tapering of blood flow from thalamus-hypothalamus towards
      medulla was observed in standing horses. Progressive significant increases in
      heart rate and in aortic and right atrial pressures occurred during exercise at 8
      and 13 m/s, and horses developed significant arterial hypoxemia and hypercapnia.
      Cerebral and cerebellar gray- to white-matter perfusion heterogeneity was
      maintained during exercise, indicating differential metabolic O2 needs. Despite
      arterial hypoxemia, hypercapnia, and hypertension, exercise did not result in
      significant changes in blood flow to the cerebral cortex and caudate nuclei
      whereas, in cerebral white matter, a significant decrease in blood flow was
      observed. In all cerebral tissues, vascular resistance increased during exercise,
      indicating autoregulation of cerebral blood flow. In the cerebellar cortex, blood
      flow increased significantly with strenuous exercise as vasodilation occurred.
      Vascular resistance in cerebellar white matter increased during exercise at 13
      m/s. Blood flow in the medulla, pons, midbrain, and thalamus-hypothalamus was not
      significantly altered during exercise from that at rest. CONCLUSION: Despite
      arterial hypoxemia, hypercapnia, and hypertension, autoregulation of cerebral and
      cerebellar blood flow is maintained in horses during exercise.

PMID- 9659559
TI  - Effects of concentrated electrolytes administered via a paste on fluid,
      electrolyte, and acid base balance in horses.
AB  - OBJECTIVES: To test effectiveness of an electrolyte paste in correcting fluid,
      electrolyte and acid base alterations in response to furosemide administration.
      ANIMALS: 6 Standardbreds. PROCEDURES: Horses received electrolyte paste or water
      only (control). The paste was given orally 3 hours after furosemide
      administration (1 mg/kg of body weight, IM). Water was given ad libitum soon
      after the paste and 3 hours after furosemide administration to treated and
      control groups, respectively. Paste Na+, K+, and Cl- composition was
      approximately 2,220, 620, and 2,840 mmol, respectively. The PCV and plasma
      concentrations of total protein ([TP]), [Na+], [K+], [Cl-]), and bicarbonate
      ([HCO3-]) were determined, and urinary fluid and electrolyte excretion, fecal
      water, and body weight changes were measured. RESULTS: At the end of a 6-hour
      period, the paste-treated group had higher water consumption, which resulted in
      lower plasma [TP]; net electrolyte losses also were substantially less. With
      paste administration, [Na+] was approximately 2 mmol/L above a prefurosemide
      value of 137.3 mmol/L; control horses had values similar to the prefurosemide
      value. Plasma [Cl-] remained at the prefurosemide value, but values in control
      horses decreased by 7 mmol/L with water consumption. Plasma [K+] remained
      approximately 0.8 mmol/L below prefurosemide values in both groups. Venous [HCO3
      ] returned to prefurosemide values after paste administration, but alkalosis
      persisted in control horses after consumption of water only. Body weight loss was
      less after paste administration. CONCLUSIONS: Administration of electrolyte paste
      is advantageous over water alone in restoring fluid, electrolyte, and acid base
      balance after fluid and electrolyte loss attributable to furosemide
      administration.

PMID- 9659560
TI  - Clinical, urodynamic, and histologic effects of urethral intussusception in
      clinically normal dogs.
AB  - OBJECTIVE: To evaluate clinical and histologic effects of surgically created
      urethral intussusception and determine whether it creates a high-pressure zone
      that resists passive urine flow in clinically normal dogs. ANIMALS: 8 healthy
      adult sexually intact female dogs. PROCEDURE: Urethral pressure profilometry was
      used to measure maximal urethral closure pressure (MUCP) and functional profile
      length (FPL) in dogs sedated with xylazine hydrochloride and atropine before and
      2, 4, 7, 14, 28, 60, and 90 days after surgery. Cystourethral leak point pressure
      (CLPP) and cystourethral leak point volume (CLPV) were determined in anesthetized
      dogs immediately before and after surgery. Dogs were assigned to 4 groups of 2
      dogs each; groups were euthanatized 4, 14, 28, and 90 days later, and
      representative tissues were examined. RESULTS: Dog 1 developed complete
      postoperative urethral obstruction. The procedure was altered, and all dogs
      recovered without complication. Mild inflammation attributable to surgical
      manipulation, but not ischemic damage or reduction of the intussusception, was
      evident. Comparison of preoperative MUCP and FPL with postoperative values did
      not yield significant differences. Immediate postoperative CLPP and CLPV were
      significantly higher than preoperative values, but were not significantly
      increased at euthanasia. A distinct but nonsignificant pressure spike was
      observed in postoperative urethral pressure profiles and persisted in 7 of 8
      dogs. CONCLUSIONS: Urethral intussusception does not have deleterious effects
      when performed as described. Urodynamic data do not support the premise that
      urethral intussusception will create a high-pressure zone in the urethra that
      will resist passive urine flow long term in clinically normal dogs.

PMID- 9659561
TI  - Effect of hyperbaric oxygen on lipid peroxidation in free skin grafts in rats.
AB  - OBJECTIVE: To document that free skin grafts treated with hyperbaric oxygen (HBO)
      are at greater risk for reperfusion injury, resulting in lipid peroxidation, than
      are free skin grafts without HBO treatment. ANIMALS: 40 Sprague-Dawley rats.
      PROCEDURE: Free skin grafting was performed bilaterally on each rat. The HBO
      treated rats received HBO twice daily for 90 minutes at 2 ATA. Biopsy specimens
      were taken from each rat at the time of grafting and on days 2, 4, 7, 10, 14, 21,
      and 28, then were processed for tissue concentration of total glutathione (GSHt),
      glutathione peroxidase activity (GPx), and presence of thiobarbituric acid
      reactive substances (TBARS). RESULTS: Both groups had a similar pattern of change
      in TBARS and GPx values--initial increase, returning to preoperative values at
      days 21 (control) and 28 (HBO). The GPx activity peaked later than did TBARS
      concentration (day 7 vs day 4). The pattern was significantly more pronounced in
      HBO-treated than in control rats. Both groups had a similar pattern of change in
      GSHt values-significant decrease from preoperative concentration at day 2, return
      to preoperative concentration by days 4 (HBO) and 7 (control), increase above
      preoperative concentration by day 21, and return to preoperative concentration by
      day 28. Obvious visual or histologic differences in the grafts were not detected
      between groups. CONCLUSIONS: Cellular effects of oxidative stress were apparent
      in both groups of rats; however, the degree of these effects was exacerbated by
      HBO. In the face of enhanced cellular lipid peroxidation, use of HBO for the
      treatment of free skin grafts must be questioned.

PMID- 9659564
TI  - Primary adenocarcinoma in an enterocutaneous fistula associated with Crohn's
      disease.
AB  - Increasing numbers of intestinal adenocarcinomas in patients with Crohn's disease
      have been reported, but the strength of this association still needs to be
      elucidated. Adenocarcinoma has also been documented in different types of
      fistulous tracts associated with Crohn's disease. The first case of well
      differentiated mucinous adenocarcinoma involving only enterocutaneous fistulae is
      reported in a patient with long-standing Crohn's disease complicated by
      persistent abdominal wall fistulous tracts. The malignant lesion arose from
      neoplastic transformation of columnar epithelium lining portions of the fistulae
      occurring as a result of either re-epithelialization of these inflammatory tracts
      or mural implantation of mucosal tissue secondary to prior ulceration. The
      patient has remained disease-free eight years after surgical resection of the
      tumour. Even though intestinal carcinoma is not as strongly associated with
      Crohn's disease as with ulcerative colitis, intestinal carcinoma should be
      considered in the setting of long-standing disease, previous intestinal exclusion
      surgeries and complications such as enterocutaneous or other types of fistulous
      tracts. The prognosis of such patients may be excellent with early diagnosis and
      treatment.

PMID- 9659565
TI  - Castleman's disease and neutropenic enterocolitis presenting as Crohn's disease.
AB  - A rare case of Castleman's disease presenting as Crohn's disease is described.
      This 21-year-old male with chronic neutropenia for one year presented with
      recurrent right lower quadrant pain of two years' duration. Small bowel follow
      through suggested Crohn's of the terminal ileum. Colonoscopy confirmed
      ulcerations in the terminal ileum and cecum, with biopsies showing necrosis and
      inflammation. Treatment was initiated with prednisone, 5-aminosalicylate and
      granulocyte colony-stimulating factor for neutropenia. Symptoms recurred one year
      later, and repeat colonoscopy showed a focal cecal ulceration. Two years after
      presentation a resection was planned. Laparotomy revealed a normal ileocecal
      region and a large retroperitoneal mass of lymphadenopathy. Biopsies confirmed
      reactive hyperplasia, consistent with the plasma cell variant of Castleman's
      disease. Chemotherapy has resulted in improvement of symptoms and decrease in
      mass size, but cecal ulceration persisted. This case illustrates a variant
      presentation of Castleman's disease with neutropenia and manifestations in the
      gastrointestinal tract.

PMID- 9659566
TI  - Ketotifen treatment of active colitis in patients with 5-aminosalicylate
      intolerance.
AB  - Mast cell stabilizers are commonly used in the treatment of asthma and allergic
      disorders. Although the role of mucosal mast cells in the pathogenesis of
      inflammatory bowel disease remains uncertain, mast cell stabilizers have been
      shown in animal models to attenuate the severity of experimental colitis. The
      authors' experience with ketotifen in three patients--one each with Crohn's
      disease, ulcerative colitis and collagenous colitis--who had demonstrated allergy
      to, or intolerance of, 5-aminosalicylic acid is reported.

PMID- 9659567
TI  - Inflammatory bowel disease with cytoplasmic-staining antineutrophil cytoplasmic
      antibody and extensive colitis.
AB  - A cohort of 18 patients with inflammatory bowel disease who were characterized by
      the presence of cytoplasmic-staining antineutrophil cytoplasmic antibody (cANCA)
      and extensive colitis is reported. Almost half were Indo-Canadians, and atypical
      perinuclear-staining antineutrophil cytoplasmic antibody was also detected in
      five (28%), similar to the detection rate for Crohn's disease and other less
      commonly detected forms of colitis, such as lymphocytic or collagenous colitis.
      Careful pathological review of all endoscopic biopsies and surgically resected
      colonic tissues did not reveal evidence of vasculitis or so-called 'palisading'
      granulomas, which is a typical pathological change of Wegener's granulomatosis,
      an entity that has been traditionally characterized by the detection of cANCA.
      This report describes 18 patients with extensive colitis and the seromarker cANCA
      but without clinical features or histological evidence of vasculitis.

PMID- 9659568
TI  - Patients' perceptions of their participation in a clinical trial for
      postoperative Crohn's disease.
AB  - OBJECTIVE: To explore patients' perceptions of their participation in a
      randomized controlled trial. PATIENTS AND METHODS: A 27-item questionnaire was
      mailed to all patients who participated in a randomized controlled trial that
      determined the effectiveness of mesalamine in preventing the recurrence of
      Crohn's disease postoperatively. RESULTS: The response rate was 66% (99 of 149).
      Fifty-five per cent of the patients felt that they received better medical care
      than they otherwise would have and 53% liked taking the medication. Sixty-eight
      per cent of the patients did not feel that annual colonoscopy was too frequent
      and 81% felt that the time commitment did not significantly interfere with their
      job or other activities. Seventy-five per cent and 62% of the patients would have
      liked more information and education, respectively, about Crohn's disease
      incorporated into the trial. Although 91% of the patients would agree to
      participate in a future randomized controlled trial comparing medical therapies,
      only 44% would agree to participate in a future randomized controlled trial
      comparing medical with surgical therapies. CONCLUSIONS: The majority of patients
      were satisfied with their participation in the trial. A large proportion of the
      patients would participate again but would like more information and education
      incorporated into the trial. Furthermore, post-trial questionnaires may be
      helpful in the design of future trials.

PMID- 9659569
TI  - Antibiotic susceptibilities of Helicobacter pylori strains isolated in the
      Province of Alberta.
AB  - The incidence of antibiotic resistance to amoxicillin, clarithromycin,
      erythromycin, metronidazole and tetracycline in Helicobacter pylori strains
      isolated from gastric biopsy specimens obtained in Alberta was investigated.
      Results for all antibiotics were obtained using agar dilution, and in addition to
      metronidazole, the E test was used. Resistance to amoxicillin and tetracycline
      was not detected. Metronidazole resistance determined using agar dilution was
      approximately 12% (95% CI 4% to 26%) when minimal inhibitory concentrations
      (MICs) were at least 8 micrograms/mL, but fell to 2% (95% CI 0.1% to 13%) when
      MICs were set at 32 micrograms/mL or greater. The E test for metronidazole
      resistance (MIC 8 micrograms/mL or greater) yielded a slightly higher percentage
      of resistant strains compared with agar dilution tests (14%, 95% CI 5% to 29%).
      One of the 31 strains was resistant to clarithromycin (MIC 8 micrograms/mL) and
      erythromycin (MIC 16 micrograms/mL). Thus, the incidence of resistance to
      clarithromycin, part of the currently used triple therapy for eradication of H
      pylori, was 3% (95% CI 0.1% to 17%).

PMID- 9659570
TI  - High-dose chemotherapy and autologous bone marrow or stem cell reconstitution for
      solid tumors.
AB  - High-dose chemotherapy--in conjunction with the transplantation of either
      mononuclear cells harvested from the marrow or CD 34+ cells harvested from the
      peripheral blood--has proved effective in curing certain patients with leukemia,
      lymphoma, and, to a lesser extent, multiple myeloma. Though the CD 34+ therapy is
      a relatively new treatment and the mononuclear cell therapy is more standard,
      both have been successfully used to reconstitute lethally damaged hematopoietic
      stem cells. Allogeneic transplants have been more effective than autologous
      transplants against tumors, but they also pose a greater hazard of death from
      complications, graft-versus-host disease, and infections. More currently, this
      approach has been used in patients with certain solid tumors, either in a
      metastatic or recurrent disease setting or as an adjuvant to surgery and/or
      standard doses of chemotherapy in patients with a known high risk of recurrence.
      Unfortunately, the majority of the studies about the impact of this therapy have
      been small and nonrandomized against standard therapy, and they have encompassed
      diverse populations of patients. This makes comparisons with contemporary
      standard--dose approaches--already problematic from a statistical point of view-
      even more dangerous because of the dissimilarity of the groups being compared.
      Particularly in the high-risk adjuvant setting, data suggest that those patients
      that meet the eligibility criteria for high-dose therapy and transplantation
      exhibit the prognostic factors for a positive outcome. When one compares these
      results with those of a more heterogeneous group of patients treated with
      conventional therapy, the conclusion might be drawn that high-dose therapy is
      superior to standard therapy, when a longer follow-up of the patients in the
      study will show this to be untrue. Thus there is a plea from clinicians and
      physicians conducting trials for prospective, randomized trials that would allow
      a fair comparison between high-dose therapy in combination with transplant
      procedures and a more conventional, standard chemotherapy, which is often less
      toxic and definitely less expensive. This article reviews the data for
      transplantation in four tumors: breast cancer, ovarian cancer, small-cell lung
      cancer, and germ cell testis cancer. There is such a small number of randomized
      trials that an attempt must be made to compare these small high-dose therapy
      studies with similar, though not identical, large studies of conventional
      therapy. This article attempts to make those comparisons, and several conclusions
      are drawn, which are detailed below. First, few data support the use of high-dose
      chemotherapy in any patient with recurrent and drug-resistant breast cancer or
      ovarian cancer. Similarly, few data support the use of high-dose approaches for
      patients with extensive small-cell lung cancer. For patients with metastatic
      breast cancer that has responded completely to conventional chemotherapy, no data
      suggest a survival advantage for the immediate consolidation of that response
      with high-dose chemotherapy. The only trial addressing this issue found that
      immediate transplantation led to a better disease-free survival rate, but overall
      survival, as compared with that of patients who received transplants at relapse,
      was not affected, and the study did not address the issue of the relative merits
      of conventional chemotherapy in either case. The only study of high-dose versus
      conventional chemotherapy was statistically underpowered, and it showed poorer
      than-anticipated outcomes in the patients who received conventional therapy.
      Ongoing or recently completed trials will, it is hoped, address the many
      unanswered questions in this area. For patients with high-risk, non-metastatic
      breast cancer, no completed and analyzed phase III randomized studies address the
      relative merits of conventional versus high-dose therapy. (ABSTRACT TRUNCATED)

PMID- 9659571
TI  - Introduction to mouse lung tumorigenesis.
AB  - This article provides a brief overview of some of the characteristics of lung
      tumors in mice and their application for studies in both chemical and molecular
      carcinogenesis and in cancer chemoprevention. The reader is referred to the above
      mentioned review articles, and the articles to follow in this issue, for more
      extensive discussions of mouse lung tumorigenesis. It has been very exciting and
      rewarding to observe the progress made by many dedicated scientists in the field
      of mouse lung tumorigenesis during the past several years, and I hope that the
      next few years will be even more exciting.

PMID- 9659572
TI  - Tobacco smoke as a mouse lung carcinogen.
AB  - Male and female strain A/J mice were exposed to environmental tobacco smoke that
      was generated by burning Kentucky 1R4F reference cigarettes. Exposures lasted 6
      hours per day, 5 days per week for a total of 5 months, followed by a 4-month
      recovery period in air. Chamber concentrations of total suspended particulate
      matter (TSP) ranged from 50 to 90 mg/m3. Under these conditions, the average lung
      tumor multiplicity was 1.2 to 1.4 tumors per lung, significantly higher (p <
      0.05) than in concomitant controls. ETS exposure led to a comparatively modest
      increase in cell proliferation in the alveolar zone during the first 2 weeks and
      in the terminal airways during the first 6 weeks. In the nasal passages cell
      proliferation was increased throughout, but reverted down to normal when the
      animals were placed in air. Smoke exposure increased immunostaining for
      cytochrome P4501A1 in airways and parenchyma. Exposure to the smoke gas phase
      only produced a similar increase in lung tumor multiplicity as did exposure to
      full smoke, but failed to induce P4501A1. This suggested that gas-phase
      constituents play an important role in tobacco smoke carcinogenesis. The strain
      A/J lung tumor model is thus suitable to study questions associated with tobacco
      smoke toxicity and carcinogenicity.

PMID- 9659574
TI  - Use of quantitative trait loci to map murine lung tumor susceptibility genes.
AB  - During the last decade new methods for mapping quantitative trait loci (QTLs)
      have helped geneticists uncover disease-associated genes. Genetic dissection of
      complex multigenic diseases such as cancer is being accomplished in part by
      mapping QTLs in experimental crosses of mice [1]. With the recent construction of
      dense genetic linkage maps for the mouse, mapping of quantitative trait loci has
      become practical [2]. Over 6000 polymorphic simple sequence length repeat markers
      (microsatellite markers) have been mapped in the mouse genome [3], and new
      analytical approaches to linkage analysis have made QTL mapping a powerful
      technique for identifying cancer genes [4-7]. In this overview we discuss the
      design of QTL mapping studies and some of the findings from studies on the
      mapping of murine lung tumor susceptibility loci.

PMID- 9659573
TI  - Mechanistic relationships between DNA adducts, oncogene mutations, and lung
      tumorigenesis in strain A mice.
AB  - This paper describes a series of studies on the lung tumorigenic activities of
      polycyclic aromatic hydrocarbons (PAHs) in strain A/J mice, their ability to form
      PAH-DNA adducts in lung tissues, and their ability to mutate the Ki-ras oncogene
      in PAH-induced tumors. Seven PAHs were studied: cyclopenta[cd]pyrene (CPP),
      benzo[a]pyrene (B[a]P), benzo[b]fluoranthene (B[b]F), dibenz[a,h] anthracene
      (DBA), 5-methylchrysene (5MC), benz[j]aceanthrylene (B[j]A), and
      dibenzo[a,l]pyrene (DB[a,l]P). The dose-response data for the PAHs revealed 100
      fold differences in tumor potency based on dose, with the order of activity
      DB[a,l]P, DBA > B[j]A > 5MC > CPP B[a]P > B[b]F. Large differences in tumor
      multiplicity were also observed between the PAHs. DNA adducts were measured by
      32P-postlabeling techniques on DNA from lungs of mice treated with these PAH's.
      DB[a,l]P gave syn- and anti-fjord-region diol-epoxide adducts of dAdo and dGuo;
      DBA gave both bay-region diol-epoxide-dGuo and bisdihydrodiol-epoxide adducts;
      CPP gave cyclopenta-ring-dGuo adducts; B[j]A gave a mixture of cyclopenta-ring
      dGuo and -dAdo adducts; 5MC gave anti-bay-region diol-epoxide-dGuo adducts; B[a]P
      gave bay-region diol-epoxide-dGuo adducts; and B[b]F gave 5-hydroxy-B[b]F-diol
      epoxide-dGuo adducts. Ki-ras codon 12 and 61 mutation analysis of PAH induced
      tumors was performed using PCR and dideoxy sequencing methods. DB[a,l]P gave both
      codon 12 and codon 61 mutations. High proportions of codon 12 TGT mutations from
      B[a]P-, B[b]F- and 5MC-, induced tumors and CGT mutations from CPP- and B[j]A
      induced tumors were observed. DBA produced no mutations in Ki-ras codons 12 or 61
      by direct sequencing. The interrelationships between the tumorigenesis, DNA
      adduct, and oncogene mutation data are discussed.

PMID- 9659575
TI  - Genetics of quantitative and qualitative aspects of lung tumorigenesis in the
      mouse: multiple interacting Susceptibility to lung cancer (Sluc) genes with large
      effects.
AB  - Inbred strains of mice exhibit large differences in their susceptibility to
      various complex quantitative genetic traits, among which is the susceptibility to
      lung cancer. These differences are caused by the combined effects of multiple
      quantitative trait loci (QTLs). Due to their multiplicity, it is relatively
      difficult and laborious to study the effects of individual QTLs. To dissect
      complex genetic traits the authors make use of recombinant congenic strains
      (RCS), a system of mouse inbred strains in which the genetic complexity is
      reduced. The susceptibility to lung cancer is studied by using the series of O20
      congenic-B10.O20 (OcB) RC strains. They are derived from the parental background
      strain O20 and the parental donor strain B10.O20, two mouse inbred strains that
      differ from each other in both quantitative and qualitative aspects of lung
      tumorigenesis. This study describes the segregation of lung tumor number, size,
      and histology among the OcB RC strains, and indicates that these traits are
      influenced by multiple interacting QTLs with considerable individual effects. The
      results suggest that some of the susceptibility loci to lung cancer affect the
      susceptibility to other types of cancer as well, possibly by functioning
      systematically.

PMID- 9659576
TI  - Analysis of the Mom1 modifier of intestinal neoplasia in mice.
AB  - Although the methodology for mapping genes controlling susceptibility to tumor
      development in mice is becoming well established, it remains a formidable
      challenge to move from linkage to locus. Positional cloning, now commonly used in
      the identification of loci affecting a qualitative phenotype, has yet to be
      successfully applied to quantitative trait loci. This study describes the
      application of candidate gene testing, a method complementary to positional
      cloning. The method has been applied to evaluate candidates for the quantitative
      trait locus, Mom1, which modifies the susceptibility of ApcMin/+ mice to
      spontaneous intestinal tumor development. The authors also discuss the further
      testing of one candidate, the phospholipase gene Pla2g2a, by transgenesis.
      Finally, studies on the mode of action of Mom1 are discussed in light of the
      evidence that Mom1 encodes this secretory phospholipase.

PMID- 9659577
TI  - Immunohistochemical detection of CYP2E1 and 2-S-glutathionyl acetate in murine
      lung tumors: diminished formation of reactive intermediates of 1,1
      dichloroethylene.
AB  - This study investigates the potential of urethane-induced lung tumors to activate
      1,1-dichloroethylene (DCE), a chemical that causes Clara cell damage in mice.
      Metabolism of DCE is catalyzed by the cytochrome P450 isozyme CYP2E1 to the DCE
      epoxide, as assessed by formation of 2-S-glutathionyl acetate (GTA), the
      glutathione (GSH)-conjugated product of the epoxide. Immunohistochemical studies
      were performed in normal non-tumor- and tumor-bearing mice to determine lung
      cells that contained CYP2E1 available for DCE metabolism. The site of GTA
      formation was also determined. The results showed that most of the CYP2E1 were
      expressed in Clara cells from normal lung and in uninvolved tissue of tumor
      bearing lung. In contrast, CYP2E1 was minimally expressed in neoplastic tissue,
      including hyperplasias, adenomas, and carcinomas. Parallel studies of adjacent
      lung sections revealed that GTA immunostaining was most intense in Clara cells of
      normal lung tissue and in uninvolved tissue of tumor-bearing lungs from DCE
      treated mice. However, GTA staining was negligible at all tumor sites. These
      results demonstrated that the cellular sites where CYP2E1 was expressed were the
      same as those in which the GTA metabolite was identified. They further showed
      that expression of both CYP2E1 and GTA was markedly reduced in hyperplasias,
      adenomas, and carcinomas. These observations suggest that these tissue types are
      defective in their capability for bioactivation of DCE.

PMID- 9659578
TI  - Role of the cytosine DNA-methyltransferase and p16INK4a genes in the development
      of mouse lung tumors.
AB  - CpG island methylation is an epigenetic modification of DNA associated with the
      silencing of gene transcription. The p16INK4a (p16) tumor suppressor gene is
      inactivated in human non-small cell lung cancers (NSCLCs) by either homozygous
      deletion or aberrant methylation. Inactivation of tumor suppressor genes by
      methylation has been linked in part to altered activity of the cytosine DNA
      methyltransferase (DNA-MTase), the enzyme that catalyzes DNA methylation at CpG
      sites. The purpose of these studies was to define the role of DNA-MTase and p16
      in the development of murine lung cancer. DNA-MTase activity was determined in
      alveolar type II and Clara cells from A/J and C3H mice that exhibit high and low
      susceptibility, respectively, for lung tumor formation. Increased DNA-MTase
      activity leading to an increase in overall DNA methylation was found only in
      alveolar type II cells, the target for murine adenocarcinomas. Both DNA-MTase and
      DNA methylation changes were detected 7 days after carcinogen exposure and, thus,
      were early events in neoplastic evolution. In addition, enzyme activity increased
      incrementally during lung cancer progression. Expression of p16 was detected in
      all primary lung tumors from A/J mice; however, levels of expression differed by
      up to 15-fold between tumors. The apparent low levels of expression seen in
      approximately half of the tumors was not attributed to methylation of the p16
      gene. In contrast to the detection of p16 expression in primary tumors, this gene
      was deleted in four tumor-derived cell lines induced in the A/J mouse by NNK. The
      results from these studies indicate that the modulation of DNA-MTase activity was
      cell specific, segregated with susceptibility, and occurred early in neoplastic
      evolution. Thus, the marked increase in enzyme activity detected in alveolar type
      II cells after carcinogen treatment could be a major factor contributing to the
      high susceptibility for chemical-induced neoplasia associated with the A/J mouse
      strain. The inactivation of the p16 gene in murine cancers induced by NNK most
      likely arises as a late event via homozygous deletion.

PMID- 9659579
TI  - Additional evidence that the K-ras protooncogene is a candidate for the major
      mouse pulmonary adenoma susceptibility (Pas-1) gene.
AB  - A locus for mouse pulmonary adenoma susceptibility, Pas-1, has been mapped on
      distal chromosome 6, where the K-ras gene is located. Allele-specific activation
      and expression of the K-ras allele from the susceptible parent has been observed
      in lung tumors from F1 hybrid mice. We report here genetic mapping of lung tumor
      susceptibility genes in urethane-treated A x B and B x A recombinant inbred (RI)
      mice using microsatellite markers to seek further evidence for the K-ras gene as
      candidate for Pas-1. The K-ras genotype differs between the A/J and C57BL/6J
      progenitors of the RI strains, and distal chromosome 6 contained a major lung
      tumor susceptibility determinant in the RI mice. Additional evidence that Pas-1
      is K-ras involved linkage analysis of (A/JOLaHsd x BALB/ cOLaHsd) F2 intercross
      mice whose parents shared the same K-ras genotype. In contrast to the results
      with the A x B and B x A RI strains, no distal chromosome 6 site was
      significantly associated with tumor development in these F2 mice. In addition to
      this major locus, linkage analysis of the RI mice revealed additional
      quantitative trait loci for susceptibility on chromosomes 10, 17, and 19. These
      loci may serve as modifiers of Pas-1. The relationship between the K-ras genotype
      and the frequency of K-ras mutations in urethane-induced lung tumors from the RI
      mice was also explored. All 18 tumor DNAs from RI mice with high susceptibility
      contained an AT-->TA transversion at the second base of K-ras codon 61. This was
      also true for DNAs from 27 of 27 (100%) tumors in mice with high intermediate
      susceptibility. In RI strains with a low intermediate susceptibility, the DNA
      from 39 of 47 (83%) tumors contained an AT-->TA transversion at codon 61, and
      only 13 of 21 (62%) tumors had this mutation in the most resistant group. This
      reflects a positive correlation between the frequency of K-ras mutations in lung
      tumors of A x B or B x A RI strains and their susceptibility to lung
      carcinogenesis. Since K-ras appears to be Pas-1, these results suggest that some
      RI mice that have the resistant K-ras or Pas-1 allele undergo tumor development
      by a K-ras-independent route.

PMID- 9659580
TI  - Expression of cell cycle proteins in 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanone-induced mouse lung tumors.
AB  - Cyclin D1 dysregulation and differential inactivation of p16INK4a and Rb have
      been observed in human lung cancer. In chemically induced mouse lung tumors, the
      p16INK4a gene is a target of inactivation, and Rb is reduced at the mRNA level
      (Northern blot) although similar at the protein level (Western blot) when
      compared to normal lung tissues. The expression of cyclin D1, cdk4, p16INK4a, and
      Rb protein was examined by immunohistochemistry in 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone (NNK)-induced mouse lung tumors. Immunohistochemical staining
      revealed exclusive nuclear staining of both cyclin D1 and cdk4 that was light to
      moderate in normal mouse lung tissues, but intense in lung adenomas and
      adenocarcinomas. Western blot analysis confirmed the increased expression of
      cyclin D1 and cdk4 in lung tumors compared to normal lung. Immunohistochemical
      analyses of lung tumors showed focal areas which lacked p16INK4a staining.
      Expression of p16INK4a, as determined by RT-PCR, was variable in lung tumors.
      Mutations in p16INK4a were not found by SSCP analysis. Immunohistochemical
      analyses of normal lung tissues showed intense staining for Rb protein in
      alveolar epithelial cells and in other lung cell types; however, in the lung
      tumors the staining intensity was reduced and the distribution was altered.
      Expression of Rb was detected in normal lung tissues but was barely detectable by
      Northern blot hybridization in lung tumors. Western blot analysis indicated the
      presence of both hypophosphorylated and hyperphosphorylated Rb protein in lung
      tumors and in normal lung tissues. These results suggest that alterations in the
      cell cycle proteins, cyclin D1, cdk4, p16INK4a, and Rb, may play a role in the
      acquisition of autonomous growth by adenomas. Furthermore, they demonstrate the
      importance of immunohistochemical studies to examine expression in tissues that
      contain multiple cell types, such as the lung, and in tumors that by nature are
      heterogeneous.

PMID- 9659581
TI  - Role of gap junctions in lung neoplasia.
AB  - Reduced gap junctional intercellular communication (GJIC) has been noted in many
      types of neoplastic cells and may contribute to the neoplastic phenotype. This
      study assessed GJIC (by fluorescent dye-coupling) and gap junction protein
      (connexin) expression in mouse and human lung carcinoma cell lines and
      investigated whether reduced GJIC was involved in their neoplastic phenotype. Dye
      coupling and connexin43 (Cx43) expression were much lower in most of the
      carcinoma lines (16 of 22) compared to nontransformed lung epithelial cells.
      Other connexins were not detected. A poorly communicating mouse lung carcinoma
      cell line (E9) was transfected with Cx43 or transduced with Cx32 and several
      stable clones were isolated that had 2- to 4-fold increased dye coupling. When
      evaluated for growth in vitro, the population doubling times were increased and
      the saturation densities were decreased in the clones. When assessed for
      tumorigenicity, the parental E9 cells formed tumors with a 100% incidence (6/6
      mice), whereas the clones varied in tumorigenic response (0-88% incidence). The
      best communicating clone (E9-2) was not tumorigenic. The highly communicating
      Cx32 clone, E9/32-9, gave a tumor incidence of 88%. These results suggest that
      restoration of GJIC by forced connexin expression can reduce the growth and
      tumorigenicity of lung carcinoma cells in a connexin-specific manner.

PMID- 9659582
TI  - Molecular comparison of human and mouse pulmonary adenocarcinomas.
AB  - Mice develop lung tumors similar in their histogenesis and molecular features to
      peripheral adenocarcinomas in humans. The advantage of this model system is that
      events early in tumorigenesis can be delineated and their biological consequences
      tested by transgenic and knockout strategies. Both human and murine
      adenocarcinomas contain Kras mutations; in mice these occur within weeks
      following carcinogen administration. Decreased expression of similar tumor
      suppressor genes occur in both species due to mutation, deletion, altered DNA
      methylation, or unknown mechanisms. These genes include p15, p16, Rb, cyclin D1,
      p53, Apc, Mcc, and Gjal. Some genes have only been examined in one of these
      species, such as the deletions in chromosome 3p and the overexpression of bcl 2
      in human adenocarcinoma. Not all molecular changes are identical to the two
      species, however. Quinone oxidoreductase (DT-diaphorase) levels rise in the human
      tumors but fall in the mouse; the extent of both changes is very dramatic.
      Similarly, EGF-receptor content often increases in human lung adenocarcinomas but
      decreases in the mouse tumors. In general, however, the nature of the molecular
      changes is quite similar.

PMID- 9659583
TI  - Molecular pathogenesis of transplacentally induced mouse lung tumors.
AB  - Previous studies from this and other laboratories have shown that treatment of
      pregnant mice with 3-methylcholanthrene (MC) caused lung tumors in the offspring,
      the incidence of which correlated with fetal inducibility of Cyp1a1. Analysis of
      paraffin-embedded lung tissue for Ki-ras-2 mutations indicated that 79% of the
      lesions examined contained point mutations in codons 12 and 13 of the Ki-ras-2
      gene locus, the majority of which (84%) were G-->T transversions. The mutational
      spectrum was dependent on the tumor stage, as both the incidence of mutation and
      type of mutation produced correlated with malignant progression of the tumor.
      Mutations occurred in 60% of the hyperplasias, 80% of the adenomas, and 100% of
      the adenocarcinomas. In the tumors with mutations, GLY12-->CYS12 transversions
      occurred in 100% of the hyperplasias, 42% of the adenomas, and 14% of the
      adenocarcinomas. GLY12-->VAL12 transversions were not observed in hyperplasias
      and occurred in 42% of the adenomas and 57% of the adenocarcinomas. The remaining
      ASP12 and ARG13 mutations occurred only in adenomas (17%) and adenocarcinomas
      (29%). The tumors were also analyzed for alterations in the structure or function
      of the tumor suppressor genes Rb, p53, and Cdkn2a. No mutations were observed in
      exons 5-8 of the p53 gene. SSCP analysis demonstrated that 2 of 15 lung tumors
      contained shifted bands at the Cdkn2a gene locus. Sequence analysis had
      identified these as mutations in exon 2, with a CAC-->TAC transition at base 301
      (HIS74-->TYR74) in tumor 23-1 and GGG-->GAG transition at base 350 (GLY90-
      >GLU90) in tumor 36-1. Northern blot analysis of the larger tumors revealed that
      14 of 14 of these large lung tumors exhibited markedly decreased expression of Rb
      gene transcripts. These results were confirmed by immunohistochemistry. The
      larger tumors, which exhibited features of adenocarcinomas, showed a marked
      reduction or almost complete absence of nuclear pRb staining compared with
      smaller adenomas and normal lung tissue. The results suggest that Ki-ras-2
      mutations are an early and frequent event in lung tumorigenesis, and that the
      type of mutation produced by environmental chemicals can influence the
      carcinogenic potential of the tumor. The results obtained with the Cdkn2a and Rb
      genes suggest that alterations in the Rb regulatory axis may play a key role in
      the pathogenesis of the pulmonary tumors and appear to occur later in the
      neoplastic process. It appears from these experiments that the combination of
      mutated Ki-ras-2 and alterations in the Rb regulatory gene locus, which are
      frequent alterations in human lung tumors, may be the preferred pathway for lung
      tumor pathogenesis in mice exposed transplacentally to environmental carcinogens.

PMID- 9659584
TI  - Transforming growth factor-beta expression in mouse lung carcinogenesis.
AB  - Transforming growth factor-beta (TGF-beta) is a multifunctional growth modulator
      that inhibits the proliferation of many epithelial cells while stimulating the
      proliferation of most fibroblasts. To examine the role of TGF-beta in mouse lung
      chemically induced tumorigenesis, expression of the TGF-beta 1, -beta 2, and 
      beta 3 proteins was examined in A/J mice treated with the carcinogen urethane to
      induce lung adenomas using immunohistochemical staining analysis. Immunostaining
      for the TGF-beta ligands was detected in the epithelium of the bronchioles of
      untreated A/J mice with immunostaining being more intense for TGF-beta 1 than for
      TGF-beta 2 and TGF-beta 3; immunostaining for each TGF-beta ligand was also
      detected in the bronchiolar epithelium of urethane-treated A/J mice at levels
      similar to untreated mice. Immunostaining for the TGF-beta ligands was also
      detected in adenomas by 2 months; staining for TGF-beta 1, -beta 2, and -beta 3
      in adenomas was detected at levels comparable with bronchioles. Following
      treatment with urethane for 8 months, immunostaining for TGF-beta s 1, 2, and 3
      in bronchioles persisted at levels comparable to that in normal bronchioles and
      also persisted in adenomas, with staining for the TGF-beta ligands being very
      prominent on the edge of the tumor. Expression of TGF-beta 1 mRNA was examined in
      urethane-treated mouse lung tissue using Northern blot hybridization; here,
      expression of TGF-beta 1 mRNA increased 2-fold in 3-month urethane-treated lung
      tissue and an additional 2.5-fold by 8 months following urethane administration.
      Expression of TGF-beta 1 mRNA was also examined in nontumorigenic and tumorigenic
      mouse lung cells; in these cells, expression of TGF-beta 1 mRNA was higher in the
      tumorigenic cells than in the nontumorigenic cell line. These data show that
      there is an increase in expression of TGF-beta 1 during tumorigenesis and suggest
      that TGF-beta may play an important role in mouse lung carcinogenesis induced by
      urethane.

PMID- 9659585
TI  - Inhibition of NNK-induced lung tumorigenesis by modulators of NNK activation.
AB  - NNK, a tobacco-specific nitrosamine, is a potent lung carcinogen in A/J mice. One
      possible mechanism of reducing NNK-induced lung tumorigenesis is decreased
      delivery of NNK to lung as a result of enhanced hepatic CYP activity.
      Pretreatment with 13C, a known CYP inducer, results in inhibition of tumor
      multiplicity, decreased DNA adducts in lung, and increased DNA adducts in liver,
      due to induction of hepatic activation of NNK. A more preferable means of
      inhibition of NNK tumorigenesis involves direct inhibition of CYP enzymes
      responsible for NNK activation in lung. The arylalkyl isothiocyanates PEITC,
      PPITC, PBITC, PPeITC, and PHITC are effective inhibitors of NNK-induced lung
      tumorigenicity and DNA adduction. PEITC inhibits NNK-induced lung tumors at a
      dose of 5 mumol/day, but not at doses of 1 or 0.2 mumol/day. PPITC, PBITC,
      PPeITC, and PHITC are considerably more potent inhibitors than PEITC, resulting
      in significant reductions in tumor multiplicity at doses of 0.2 mumol/day. For
      these compounds, there is a good correlation between inhibition of tumor
      multiplicity and inhibition of pulmonary O6-methylguanine. LIM, previously shown
      by Wattenberg to be an effective inhibitor of NNK-induced lung tumors, and other
      monoterpenes are good inhibitors of NNK activation in vitro or in vivo. Thus,
      compounds that modulate the metabolic activation of NNK can be potent inhibitors
      of NNK tumorigenesis.

PMID- 9659586
TI  - Inhibition of lung tumorigenesis by NSAIDS: a working hypothesis.
AB  - A 7-week treatment with the tobacco carcinogen NNK induced 8-10 lung adenomas per
      A/J mouse. NNK suppressed humoral and cellular immune responses and increased
      plasma PGE2 and LTB4 levels. This protocol is particularly suitable for testing
      NSAIDs and lipoxygenase inhibitors as cancer preventive agents. Sulindac and ASA
      inhibited lung tumorigenesis by 52 and 60%, respectively, attenuated the
      suppressive effect of NNK, and lowered the plasma PGE2 to basal levels. In
      contrast, naproxen neither inhibited lung tumorigenesis nor increased NNK
      suppressed NK cell cytotoxicity. NSAIDs and lipoxygenase inhibitors had additive
      preventive efficacies against NNK-induced lung tumorigenesis. However, sulindac
      was not effective in preventing lung tumorigenesis induced by B[a]P, which lacks
      immunosuppressive activity. These results and those published by other
      investigators lead to the following hypothesis: Reactive intermediates derived
      from NNK interfere with the stimulation of the complex NF-kappa B/I kappa B. NF
      kappa B is involved in the regulation of immune and inflammatory responses. The
      authors propose that NNK-derived intermediates induce the expression of COX-2 and
      lipoxygenase involved in NNK activation. This hypothesis provides a rationale for
      the lack of efficacy of naproxen to prevent tumorigenesis, to attenuate NNK
      induced synthesis of PGE2, and to increase NK cell cytotoxicity. According to
      this hypothesis, PGE2 synthesis and induction of apoptosis contribute to varying
      degrees to the mechanism of cancer prevention.

PMID- 9659587
TI  - Lipoxygenase inhibitors prevent lung carcinogenesis and inhibit non-small cell
      lung cancer growth.
AB  - The effects of lipoxygenase inhibitors were investigated using human lung cancer
      cell lines and A/J mice. By RT-PCR, 5-, 12-, and 15-lipoxygenase mRNA was
      detected in NSCLC cells. NDGA inhibited 5-LO activity in adenocarcinoma cell line
      NCI-H1264. Using an MTT assay, NDGA, MK591 and AA861 inhibited the growth of
      NSCLC cell lines tested with IC50 values of 3, 2, and 7 microM, respectively.
      Using a clonogenic assay, 10 microM NDGA significantly reduced NSCLC colony
      number. NDGA significantly slowed NSCLC xenograft growth in nude mice. When the
      tumors were excised and analyzed, nude mice treated with NDGA had significantly
      more apoptotic figures than did untreated tumors. A/J mice treated with urethane
      developed adenomas after 4 months and NDGA administration significantly reduced
      lung adenoma number. These data indicate that lipoxygenase inhibitors inhibit
      lung cancer growth and prevent lung carcinogenesis.

PMID- 9659588
TI  - Tea and tea polyphenols inhibit cell hyperproliferation, lung tumorigenesis, and
      tumor progression.
AB  - Both green and black tea have been shown to inhibit lung tumorigenesis in
      laboratory animal experiments. Green tea inhibited N-nitrosodiethylamine-induced
      lung tumor incidence and multiplicity in female A/J mice when tea was given
      either during the carcinogen treatment period or during the post-carcinogen
      treatment period. In a separate tumorigenesis model, both decaffeinated black tea
      and decaffeinated green tea inhibited 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanone (NNK)-induced lung tumor formation. Studies in which tea was
      administered during different time periods in relation to the NNK suggest that
      tea can inhibit lung tumorigenesis at both the initiation and promotion stages.
      The antiproliferative effects of tea may be responsible for these anti
      carcinogenic actions. Black tea polyphenol preparations decreased NNK-induced
      hyperproliferation. Black tea also inhibited the progression of pulmonary
      adenomas to adenocarcinomas and the formation of spontaneous lung tumors in A/J
      mice. Growth inhibition by various tea polyphenols has been demonstrated in human
      lung H661 and H1299 cells. Although inhibition of cell growth and signal
      transduction pathways by tea components have been demonstrated, the
      concentrations required to produce the effect are higher than achievable in
      tissues in vivo. More research is necessary to translate these laboratory results
      to applications in human chemoprevention.

PMID- 9659589
TI  - Magnetic resonance imaging of hypoxic-ischemic brain injury in the neonatal rat.
AB  - RATIONALE AND OBJECTIVES: Magnetic resonance (MR) imaging was used for the in
      vivo evaluation of bihemispheric hypoxic-ischemic (HI) injury in the neonatal
      rat. METHODS: Seven-day-old rats underwent sham surgery (n = 7) or bilateral
      carotid artery ligation and hypoxia (30-45 min) (n = 8). T2-weighted imaging was
      used to study the temporal evolution of injury. Histopathology was used to
      correlate injury with MR signal changes. RESULTS: T2-weighted images exhibited
      considerable anatomic detail (0.2 mm resolution in-plane). The cortex,
      dorsolateral striatum and thalamus were affected, while the hippocampus was
      spared. Magnetic resonance signal change was seen as early as 1.5 hrs post-HI
      (lesion extent, 27%-39%), and reached a maximum at 48 hrs (37%-49%). Magnetic
      resonance imaging estimation of injury at 72 hours after HI was compared with
      histopathology and correlated well (r = 0.98). CONCLUSIONS: The study
      demonstrates the feasibility of magnetic resonance imaging for in vivo evaluation
      of neonatal brain injury and that vulnerability in the neonatal hippocampus is
      strikingly different than in adult HI models.

PMID- 9659590
TI  - Depiction of reperfused myocardial infarction using contrast-enhanced spin echo
      and gradient echo magnetic resonance imaging.
AB  - RATIONALE AND OBJECTIVES: The authors used gadolinium (Gd) chelate as a T1, T2,
      and T2* enhancing agent in reperfused myocardial infarction to compare the
      appearance of reperfused myocardial infarction on spin echo and gradient echo
      magnetic resonance (MR) sequences. METHODS: Rats (n = 28) were subjected to
      reperfused myocardial infarction and received no contrast medium, 0.2, 0.5, or
      1.0 mmol/kg Gd DTPA-BMA. Spin echo and gradient echo MR images of the excised
      hearts (n = 7 rats per group) were acquired using 2.0 T system: repetition time
      (TR)/echo time (TE) = 300/20 ms for T1-weighted spin echo, TR/TE = 4000/80 ms for
      T2-weighted spin echo, and TR/TE = 600/10, 15, 20, and 30 ms for gradient echo
      imaging. Regional T2 and T2* relaxation times were measured. Triphenyl
      tetrazolium chloride was used to verify regional infarction. RESULTS: Unenhanced
      spin echo images failed to distinguish infarcted from normal myocardium. On Gd
      DTPA-BMA enhanced T1-weighted spin echo images, infarction was depicted as a high
      intensity region "hot spot." On the other hand, the infarcted region was
      visualized as a low-signal region "cold spot" on Gd DTPA-BMA enhanced T2-weighted
      images. Changes in signal intensity and T2 relaxation time on T2 weighted images
      were dose dependent. On gradient recalled echo images, the infarcted region was
      discriminated from normal myocardium by a dark boundary zone, which was visible
      only at 1.0 mmol/kg. The presence of infarction was documented in every heart.
      CONCLUSIONS: The contrast between normal and infarcted myocardium was affected
      greatly by the dose and imaging parameters. The results indicate that spin echo
      and gradient echo images have greatly differing sensitivities to extracellular
      gadolinium chelates. Changes in myocardial T2 relaxation time, but not T2*,
      correlated well with the dose.

PMID- 9659591
TI  - Comparative toxic effects of iobitridol and iohexol on the kidney.
AB  - RATIONALE AND OBJECTIVES: The authors compare the toxic effects of iobitridol and
      iohexol, which are nonionic contrast media with equivalent osmolalities and
      viscosities on the kidney. METHODS: In a rat acute renal failure (ARF) model,
      iobitridol or iohexol (both at the dose of 2.87 g I/kg) were injected to rats
      after pretreatment with indomethacin and N omega-nitro-L-arginin methyl ester.
      The effects on histopathology, creatinine clearance, and urinary N-acethyl-beta-D
      glucosaminidase (NAG) activity were assessed. In a rat renal slice system, the
      slices were exposed to iobitridol or iohexol (both at the concentration range of
      17.5-70 mg iodine/mL) for 60 min. The accumulation of para-aminohippuric acid
      (PAH), an organic anion, and the intracellular potassium content as the
      indicators of renal tubular injury were measured to assess the direct effects of
      iobitridol and iohexol on renal tubules. RESULTS: In the ARF model, no
      significant difference was detected between the effects of iobitridol and those
      of iohexol on the creatinine clearance and urinary NAG activity 24 hours after
      the injection. However, iobitridol produced a lower degree and incidence of renal
      tubular injury of renal proximal tubules (P < 0.001) and distal tubules (P <
      0.05) compared with iohexol. In the rat renal slice system, the iobitridol
      treatment had significantly less effect on the PAH accumulation compared with
      iohexol (P < 0.001). There were no changes in the intracellular potassium
      content. CONCLUSIONS: These findings suggest that iobitridol has significantly
      less toxic effects on the kidney compared with iohexol under the condition of our
      experiment.

PMID- 9659592
TI  - Evaluation of the triangular fibrocartilage and the scapholunate and
      lunotriquetral ligaments in cadavers with low-field-strength extremity-only
      magnet. Comparison of available imaging sequences and macroscopic findings.
AB  - RATIONALE AND OBJECTIVES: The authors assessed the ability of a low-field
      strength extremity-only magnet to provide visualization of the triangular
      fibrocartilage and the scapholunate and lunotriquetral ligaments. METHODS: Twelve
      human wrists were examined with a 0.2 T extremity-only magnet. T1-weighted spin
      echo, proton density-weighted, and T2-weighted turbo spin echo, short-tau
      inversion recovery, and three-dimensional gradient recalled echo images were
      acquired, and sections of the specimens were then made that corresponded to the
      magnetic resonance images. Masked imaging analyses were correlated with
      macroscopic and limited histopathologic findings. RESULTS: Low-field-strength
      extremity-only magnet allowed consistent visualization of the triangular
      fibrocartilage and accurate assessment of a small number of complete tears of the
      triangular fibrocartilage. The scapholunate ligaments in all cases were
      identified using a combination of imaging sequences. Consistent visualization of
      the lunotriquetral ligament with a low-field-strength extremity magnet was
      difficult. CONCLUSIONS: Magnetic resonance imaging with a low-field-strength
      extremity-only magnet can be used to visualize the triangular fibrocartilage and
      the scapholunate ligament, but not the lunotriquetral ligament.

PMID- 9659593
TI  - An experimental study on thrombogenicity of various metallic microcoils with or
      without thrombogenic coatings.
AB  - RATIONALE AND OBJECTIVES: Various metallic microcoils have been used as effective
      embolic materials (stainless steel, tungsten, and platinum). It also has been
      reported in several articles that the thrombogenicity of coils increased after
      soaking in thrombin solutions. To compare the thrombogenicity, the authors
      performed in vitro study, measuring whole blood clotting time (WBCT) of the
      various microcoils with and without coating with thrombin, gelatin, or both
      gelatin and thrombin. METHODS: Stainless steel, tungsten, and platinum microcoils
      were used in the study. For thrombin coating, the microcoils were soaked in 4
      U/mL thrombin solution for 5 minutes, dried for 30 minutes, then soaked and dried
      again. For gelatin coating, the microcoils were soaked in 10% gelatin solution
      for 15 minutes, dried for 30 minutes, then soaked and dried again. For dual
      coating with both gelatin and thrombin, they were soaked in 10% gelatin solution
      first for 15 minutes, dried for 45 minutes, and soaked in 4 U/mL thrombin
      solution for 5 minutes, and dried. The authors introduced 1 mL of fresh blood
      immediately into the test tube containing the microcoil, and measured the time
      taken for complete coagulation of the 1 mL blood (WBCT). RESULTS: Untreated
      stainless steel, tungsten, and platinum microcoils reduced WBCT from 15.76
      minutes to 7.15, 5.64, and 7.27 minutes, respectively. Stainless steel microcoils
      after soaking in thrombin, gelatin, and both gelatin and thrombin solutions
      showed WBCT of 5.77, 5.82, and 4.44 minutes, respectively. Tungsten microcoils
      after soaking in thrombin, gelatin, and both gelatin, and thrombin solutions
      showed WBCT of 3.25, 4.95, and 3.67 minutes, respectively. Platinum microcoils
      after soaking in thrombin, gelatin, and both gelatin and thrombin solutions
      showed WBCT of 5.70, 10.01, and 6.27 minutes, respectively. CONCLUSIONS:
      Untreated tungsten microcoils showed superior clot promoting activity compared
      with untreated stainless steel and platinum microcoils. Clot promoting activity
      of microcoils was increased after coating with thrombin, or both gelatin and
      thrombin compared with untreated microcoils.

PMID- 9659594
TI  - Dynamic gadolinium DTPA-enhanced magnetic resonance of intravascular stents.
AB  - RATIONALE AND OBJECTIVES: Magnetic resonance contrast enhancement depends on the
      timing of image acquisition. Human trials have demonstrated efficacy of renal
      artery stents on salvage of renal function. This study assessed the ability of
      dynamic gadolinium (Gd)-DTPA administration to demonstrate renal and iliac artery
      stent patency compared to conventional angiography as the gold standard. METHODS:
      Seven subjects with eight stents referred for angiography underwent dynamic
      magnetic resonance studies, all with renal artery stenting. All were examined
      with conventional angiography and after dynamic Gd-DTPA infusion. Coronal
      magnetic resonance images were acquired using a GE Signa 1.5 T magnet (fast
      spoiled gradient echo; echo time = 4.2 ms; repetition time = 68-150 ms; flip
      angle = 75 degrees) 0 to 600 seconds after 0.1 mmol/Kg Gd-DTPA intravenous bolus
      injection during sequential breath-hold acquisitions 13 to 32 seconds each.
      RESULTS: All eight stents were visualized with 100% accurate patency
      documentation. CONCLUSIONS: Fast spoiled gradient echo magnetic resonance imaging
      with bolus Gd-DTPA administration can provide adequate time and spatial
      resolution to demonstrate arterial stent patency.

PMID- 9659595
TI  - Magnetic resonance diagnosis of the anterior labrum and capsule. Effect of field
      strength on efficacy.
AB  - RATIONALE AND OBJECTIVES: The authors compare the performance of high-field and
      low-field magnetic resonance (MR) systems in the evaluation of shoulder
      instability, 35 patients were examined at field strengths of 1.0 T and of 0.2 T.
      METHODS: Surface coils were used in both systems. Because arthroscopy was used as
      gold standard, a preselected patient-population was obtained for the study.
      RESULTS: The sensitivity/specificity/accuracy of MR images acquired at 1.0 T for
      labrum pathology were 91%/67%/91% and 70%/80%/71% for the capsular complex.
      Compared with the above, the sensitivity/specificity/accuracy for 0.2 T MR images
      revealed 91%/67%/91% for the labrum pathology and 63%/80%/66% for the capsular
      complex respectively. In the evaluation of capsular lesions a comparison between
      the 0.2 T MR system and the 1.0 T system indicated a higher sensitivity and
      accuracy for the high-field images. Concerning labral lesions, the sensitivity
      and accuracy of the 0.2 T MR imager and the 1.0 T imager were comparable.
      CONCLUSIONS: Given differences in imaging protocols, imaging at 0.2 T does not
      adversely affect the assessment of shoulder instability when compared with
      imaging at 1.0 T. These preliminary results warrant more extensive clinical
      comparison of results obtained at different magnetic field strengths.

PMID- 9659596
TI  - Direct magnification technique for cerebral angiography in the rat.
AB  - RATIONALE AND OBJECTIVES: The authors evaluated the performance of direct
      magnification radiography (DIMA) with digital image processing for cerebral
      angiography in the rat. METHODS: A microfocal x-ray unit with a focal spot of 5
      microns was used for cerebral angiography in 10 rats. The animals were examined
      form x 4 up to x 20 magnification after injection of 0.2 mL x-ray contrast medium
      into the common carotid artery. RESULTS: Direct magnification radiography
      technology provides high resolution images and enables the visualization of very
      small vessels with high quality. It allows the peripheral branches of the middle
      cerebral artery or the ophthalmic artery to be visualized. Superimposition and
      noise effects can be excluded with digital subtraction and image processing.
      CONCLUSIONS: The experiments show that DIMA radiography is a suitable technique
      for cerebral angiography in the rat.

PMID- 9659597
TI  - Aminated polysaccharides as bile acid sorbents: in vitro study.
AB  - Dextran, pullulan, and microcrystalline cellulose were cross-linked with 1-chloro
      2,3-epoxypropane and reacted with N-(1-chloroethyl)-N,N-diethylamine or N
      glycidyl-N,N,N-trialkylammonium chloride in order to obtain sorbents containing
      tertiary amino and/or quaternary ammonium groups. In vitro equilibrium sorption
      of cholic acid on these sorbents was studied in comparison with Cholestyramine,
      and in vitro dissociation of ionic complexes of cholic acid-sorbents was
      determined under dynamic conditions. The sorption capacity and the affinity of
      these sorbents for cholic acid were investigated in relation to the nature of the
      polymeric support, the swelling porosity of sorbent, the basicity of amino
      groups, and the nature of the substituents at the nitrogen atom. The maximum
      sorption capacity increases with the increase in amino group content, their
      basicity, and the length of alkyl substituents at the nitrogen atom. The affinity
      for cholic acid of all polysaccharide-based sorbents is higher than that of
      Cholestyramine. Dextran-based sorbents display the highest sorption affinity. It
      was found that there exists an optimum swelling porosity for the polysaccharide
      sorbents to attain the highest affinity for cholic acid. The dissociation rate of
      ionic complexes depends also on the nature of the polysaccharide and the swelling
      porosity and its lower for sorbents with higher sorption affinity.

PMID- 9659598
TI  - Molecular calculations of poly(ethylene glycol) transport across a swollen
      poly(acrylic acid)/mucin interface.
AB  - The transport of poly(ethylene glycol) chains than can promote mucoadhesion
      across the interface between lightly cross-linked poly(acrylic acid) and mucin
      may be analyzed as a function of molecular characteristics using theories of
      chain penetration in a dilute network. The fracture energy for the ensuing
      adhesive bond is proportional to the number of polymer chains crossing the
      interface, which, in turn, is related to the polymer volume fraction, the chain
      diffusion coefficient, and the degree of polymerization. Relevant calculations
      were performed for a number of cross-linked poly(acrylic acid) gels and three
      different types of poly(ethylene glycol) chains.

PMID- 9659599
TI  - Mechanistic aspects of blood-contacting properties of polypropylene surfaces-
      from the viewpoint of macromolecular entanglement and hydrophobic interaction via
      water molecules.
AB  - Polypropylene surfaces with a particular crystalline-amorphous microstructure
      have been demonstrated to reduce protein adsorption and platelet activation. Such
      blood-contacting properties may be affected by the crystalline-amorphous
      microstructure of the surfaces, although wettability such as dynamic contact
      angles and surface free energy components were almost constant, being independent
      from the variation in the microstructure. In order to clarify the mechanistic
      aspects on their blood-contacting properties, the physicochemical properties of
      the surfaces were evaluated for a series of compression-molded polypropylene
      sheets in terms of the work of adhesion and the structure of sorbed water. The
      work of adhesion of the compression-molded sheets increased with decreasing
      surface layer crystallinity, presumably due to macromolecular entanglement with a
      polymeric glue used. The work of adhesion involving macromolecular entanglement
      may occur between proteins and the surfaces. Thus, a decrease in the surface
      layer crystallinity is considered to cause an increase in the protein adsorption.
      The structure of water sorbed into the sheets changed--it was more gaseous
      (isolated) at the surfaces with a higher crystallinity. This suggests that the
      hydrophobic interaction via water molecules increased with surface layer
      crystallinity, resulting in increasing protein adsorption and denaturation. Thus,
      it is considered that both macromolecular entanglement and hydrophobic
      interaction are important on the mechanistic aspects of blood-contacting
      properties of polypropylene surfaces. In order to confirm this hypothesis, the
      evaluation of the physicochemical properties and blood-contacting properties was
      also performed on a series of uniaxially drawn polypropylene films. A decrease in
      the work of adhesion and the hydrophobic interaction at the surfaces was observed
      with increasing draw ratio, and the protein adsorption and platelet activation
      were effectively prevented with increasing draw ratio. This result supports our
      hypothesis. Therefore, it is concluded that the excellent blood-contacting
      properties of polypropylene surfaces can be achieved by reducing the
      macromolecular entanglement and the hydrophobic interaction with proteins.

PMID- 9659600
TI  - Elastomers for biomedical applications.
AB  - Current topics in elastomers for biomedical applications are reviewed.
      Elastomeric biomaterials, such as silicones, thermoplastic elastomers, polyolefin
      and polydiene elastomers, poly(vinyl chloride), natural rubber, heparinized
      polymers, hydrogels, polypeptides elastomers and others are described. In
      addition biomedical applications, such as cardiovascular devices, prosthetic
      devices, general medical care products, transdermal therapeutic systems,
      orthodontics, and ophthalmology are reviewed as well. Elastomers will find
      increasing use in medical products, offering biocompatibility, durability, design
      flexibility, and favorable performance/cost ratios. Elastomers will play a key
      role in medical technology of the future.

PMID- 9659601
TI  - Quasi-biological apatite film induced by titanium in a simulated body fluid.
AB  - Commercially pure titanium (c.p.Ti) is capable of inducing the formation of a
      carbonated apatite onto its surface in a simulated body fluid (SBF) comprised of
      calcium ions, phosphate ions, and other inorganic species present in the body
      fluid. In addition to the incorporation of carbonate ions, such formed apatite
      has other important characteristics of the bone mineral phase, such as a small
      crystal size and ionic substitution by Mg2+ and Cl-. Thus, we call this apatite a
      quasi-biological apatite. The formation of the quasi-biological apatite is
      proposed to be related to TiOH groups that develop on the titanium surface
      through interaction with the SBF. The results suggest that titanium implants may
      be activated such that they can form a strong bond with bone tissue through the
      in vivo formation of apatite. Since the solution can reach any open space, the
      process discussed in this study is very suitable for coating porous titanium
      implants with a quasi-biological apatite film.

PMID- 9659602
TI  - Adhesion of different bacterial strains to low-temperature plasma-treated
      sutures.
AB  - In this study, five different bacteria with their different strains were isolated
      and characterized. Contact angles were measured by a captive-bubble technique.
      Surface-free energies were calculated from the contact angles. Hydrophobicities
      also were evaluated by rho-xylene adhesion. The zeta potentials and surface
      charges of the bacteria were obtained. The contact angles of the gram-positive
      bacteria and gram-negative bacteria were within the range of 48 degrees-69
      degrees and 43.5 degrees-55 degrees, respectively, while corresponding surface
      free energies were in the limits of 45.4-51.6 erg/cm-2 and 51.7-61.8 erg/cm-2,
      respectively. The rho-xylene adhesions were parallel to hydrophobicities defined
      by contact angles, and 32.2-80.3% and 2.3-36.6% for the gram-positive bacteria
      and gram-negative bacteria, respectively. The zeta potentials for these bacteria
      were from -650.2 to +17.5 mV and from -159.6 to -6.0 mV, respectively. Most of
      the bacteria were negatively charged, except the CNS-2 and CPS-1 strains. In the
      second part of the study, attachment of these bacteria to Vicryl sutures and
      their DMAEMA and AAc plasma-treated forms were investigated. Hydrophobic bacteria
      attached more to hydrophobic Vicryl sutures. Both plasma treatments caused
      significant drops in bacterial attachment in most cases. Effects of AAc plasma
      treatment were more pronounced.

PMID- 9659603
TI  - The effect of recombinant human bone morphogenetic protein-2 on the integration
      of porous hydroxyapatite implants with bone.
AB  - To determine if recombinant human bone morphogenetic protein-2 (rhBMP-2) can be
      adsorbed onto porous ceramic hydroxyapatite (HA) and promote the integration of
      HA to host bone, 54 subperiosteal pockets were created on the skulls of 19 adult
      Pasteurella-free white rabbits. Fourteen HA implants were saturated with saline
      and placed in subperiosteal pockets (control), 22 HA implants were saturated with
      saline and placed into subperiosteal pockets after burring 1-2 mm of calvarium to
      expose bleeding cancellous bone, and 18 HA implants were saturated with rhBMP-2
      and placed into subperiosteal pockets. The animals were sacrificed at 1 month
      with examination to determine implant mobility. Histology was used to determine
      the amount of bone growth into the implant. Of the 14 control sites, 10 implants
      were found to be freely mobile, five demonstrated host bone resorption, and only
      one exhibited bone growth into the implant. Of the 22 burred sites, eight were
      freely mobile and 10 demonstrated bone growth into the implant (p = 0.04). Of the
      18 rhBMP-2 sites, only two were freely mobile, none demonstrated host bone
      resorption, and 16 exhibited bone growth into the implant (p = 0.00002). This
      study supports the use of porous ceramic HA as a biocompatible, osteoconductive
      implant material for use in craniomaxillofacial augmentation and reconstruction.
      It also provides evidence that rhBMP-2 enhances osseointegration, thereby fixing
      the implant in position against the host-bone interface. In the clinical setting,
      osseous fixation of the implant should aid in preventing displacement, minimizing
      host bone resorption, and decreasing the incidence of extrusion.

PMID- 9659604
TI  - Healing response associated with balloon-dilated ePTFE.
AB  - Deployment of endovascular grafts composed of a metallic stent surrounded by
      expanded polytetrafluoroethylene (ePTFE) stretches the polymer beyond its
      original dimensions, altering the structural characteristics of the ePTFE. We
      hypothesized this structural modification would alter the healing response
      associated with the implant. In this study, 4 mm i.d. of ePTFE (30 microns
      internodal distance) vascular grafts were balloon dilated using angioplasty
      balloons having final diameters of 6 (1.5X), 8 (2X), 10 (2.5X), 12 (3X), and 18
      (4.5X) mm. Following balloon dilatation of the ePTFE, a circular punch (6 mm in
      diameter) was used to prepare polymer samples for implantation. The ePTFE
      circular patches were implanted within subcutaneous tissue and epididymal fat
      pads of male Sprague-Dawley rats. After 5 weeks, the implants were removed and
      analyzed for fibrous capsule formation, inflammation, and neovascularization
      associated with the material. Histological analysis revealed the formation of
      fibrous capsules only with control subcutaneous implants. The inflammatory
      response associated with subcutaneously implanted ePTFE was decreased
      significantly following balloon dilatation to at least 2.5 times the original
      diameter of the graft. In contrast, ePTFE implanted within adipose tissue
      demonstrated a significantly greater inflammatory response following balloon
      dilatation when compared to control implants. Only ePTFE balloons dilated to 6 mm
      and implanted within adipose tissue demonstrated neovascularization to any
      extent. These data suggest the structural modifications incurred by ePTFE
      following balloon dilatation dramatically affect the inflammatory response
      associated with an implant. Therefore, polymeric materials used for endovascular
      graft technology require designs that consider changes in polymer healing
      inherent to device design.

PMID- 9659605
TI  - Effects of serum protein opsonization on cytokine release by titanium-alloy
      particles.
AB  - This study tested whether macrophages respond differently to retrieved titanium
      alloy particles than they do to machined titanium-alloy particles and assessed
      whether pretreatment of machined titanium-alloy particles with human serum would
      influence macrophage activation and cytokine release in vitro. Human
      monocyte/macrophages were isolated from normal healthy donors and exposed to
      increasing concentrations of machined and retrieved titanium-alloy particles. The
      profile of cytokine release was determined by commercially available ELISA kits.
      Machined titanium-alloy particles were opsonized with human serum and added to
      macrophage cultures. Serum protein binding was confirmed by SDS-PAGE analysis.
      The results showed that machined titanium-alloy particles and retrieved titanium
      alloy particles stimulate a similar level of cytokine release when tested at
      comparable concentrations. Opsonization of the machined particles with human
      serum increased the macrophage release of cytokines in the first 12 h after
      exposure compared to nonopsonized particles. At 24 h, the opsonized particles
      stimulated significantly higher levels of cytokine release, but only at the
      greatest particle concentrations. This study demonstrates that machined titanium
      alloy induces a metabolic response in macrophages similar to that of titanium
      alloy particles retrieved from failed total hip arthroplasty. In addition, these
      data show that serum protein binding to orthopedic biomaterial debris alters the
      macrophage reaction to the particles.

PMID- 9659606
TI  - Fibronectin and avidin-biotin as a heterogeneous ligand system for enhanced
      endothelial cell adhesion.
AB  - A preadsorbed layer of "heterogeneous" integrin-dependent and -independent
      protein was used to enhance initial integrin-mediated endothelial cell attachment
      and spreading. Glass substrates were treated with fibronectin (Fn) and avidin
      coupled through adsorbed biotinylated bovine serum albumin (b-BSA). The slides
      then were seeded with biotinylated BAEC. Control "homogeneous" surfaces were
      slides adsorbed with either Fn or avidin coupled to b-BSA. The cells were
      incubated for 0.5 h in serum-containing media and exposed to a range of shear
      stresses in a laminar flow variable-height flow chamber. The critical shear
      stress to detach 50% of the seeded cells on the heterogeneous ligand surface was
      significantly greater than for either of the control homogeneous ligand systems
      (p < 0.001). Cellular spreading during the initial period of 0-2 h also was
      higher (p < 0.05) on the heterogeneous ligand-treated surface than on the surface
      of either of the homogeneous controls. The close contact area of the cell
      membrane with the substrate 1 h after seeding in serum-containing media was
      measured using TIRFM. Cells attached onto the heterogeneous ligand-treated
      surfaces had a significantly (p < 0.01) higher area of close contact with the
      substrate, which is consistent with a greater degree of attachment and spreading.
      The results indicate that the combination of integrin-dependent and -independent
      adhesion systems using heterogeneous ligands further enhances initial endothelial
      cell attachment and spreading.

PMID- 9659607
TI  - Preparation of a novel functional hydrogel consisting of sulfated glucoside
      bearing polymer: activation of basic fibroblast growth factor.
AB  - Sulfated poly(glucosyloxyethyl methacrylate) [poly(GEMA)-sulfate] and its
      hydrogel were synthesized and evaluated to develop novel tissue regeneration
      assist devices. The poly(GEMA)-sulfate hydrogel was obtained by gamma-ray
      irradiation. Basic fibroblast growth factor (bFGF) was expected to be
      subsequently incorporated with hydrogel matrices and activated or released from
      the matrices. A sustained release of bFGF from the poly(GEMA)-sulfate hydrogel
      was not realized; however, bFGF from poly(GEMA)-sulfate hydrogel was effectively
      activated. Poly(GEMA)-sulfate hydrogels are thought to be potential component
      materials for a tissue engineering matrix.

PMID- 9659608
TI  - Effect of particulate bioactive glass on human synoviocyte cultures.
AB  - Bioglass is a resorbable glass material that has been shown to induce osteoblast
      proliferation as well as bone matrix production in vitro. Its physico-chemical
      properties have been reported to be suitable for use as an implant coating for
      arthroplasty. However, Bioglass is a ceramic material that can fragment into
      particulate debris in vivo. The effect of particulate Bioglass on tissue cells
      has not been defined. In order to determine the biologic response to particulate
      Bioglass, we tested its effect on human synoviocytes in a cell culture model. At
      the concentrations of 1.0 and 10, micrograms/mL, particulate Bioglass (sizes
      ranging from approximately 0.5 to 80 microns) had a low cytotoxic effect.
      However, these concentrations induced secretion of TNF alpha. The observation
      that particulate Bioglass elicits release of inflammatory cytokines suggests that
      the development of this bioceramic implant coating should address techniques that
      would minimize the generation of particulates.

PMID- 9659609
TI  - Crystallization kinetics of a low-expansion feldspar glass for dental
      applications.
AB  - Previous studies have shown that the crystallization of glasses in the system K2O
      Al2O3-SiO2, in the primary field of leucite, is not possible without modification
      of the composition. Leucite (KAlSi2O6) is used as a reinforcing phase in some
      compositions for all-ceramic dental restorations. However, because of their
      higher coefficient of thermal expansion, these materials cannot be veneered with
      conventional metal-ceramic porcelains. The purposes of this study were to
      investigate the crystallization behavior of a glass in the system K2O-Al2O3-SiO2
      and to evaluate the effect of heat treatment on the crystal size, percent
      crystallinity, and coefficient of thermal expansion of the material. Ion
      exchanged glass powder was prepared by mixing the glass with rubidium nitrate and
      heat-treating at 450 degrees C for 4, 8, 24, or 48 h. Bars were made from these
      powders and baked under vacuum at 1038 degrees C for 2 min. The bars made from
      the powder ion-exchanged for 48 h were further heat-treated for 4 h at either 800
      degrees C, 850 degrees C, 900 degrees C, 950 degrees C, or 1038 degrees C. X-ray
      diffraction analyses showed cubic leucite was the only crystalline phase in the
      specimens made from the powders ion-exchanged for 4, 8, 24, or 48 h and baked at
      1038 degrees C for 2 min. Further heat treatment for 4 h at either 800 degrees C,
      850 degrees C, 900 degrees C, 950 degrees C, or 1038 degrees C promoted the
      growth of cubic leucite. In addition, a second phase identified as tetragonal
      rubidium-leucite was present in the specimens heat-treated for 4 h at 1038
      degrees C. SEM observations showed that all specimens made from the powders ion
      exchanged for 48 h exhibited small spherical crystals dispersed in a glassy
      matrix. The percent crystallinity ranged from 18.9% to 42.9% and the average
      particle size was between 0.64 to 1.18 microns. The coefficients of thermal
      expansion ranged between 8.076 and 8.788 x 10(-6)/degree C.

PMID- 9659610
TI  - Basic fibroblast growth factor adsorption and release properties of calcium
      phosphate.
AB  - Basic fibroblast growth factor (bFGF) is well known as a potent angiogenic factor
      playing a crucial role in wound-healing processes. Apatitic substrates such as
      hydroxyapatite and carbonated apatite (CA) could be potential carriers of growth
      factors because of their physicochemical similarities to bone mineral. These
      materials have been compared for their bFGF adsorption and release properties.
      The adsorption of the growth factor was higher on carbonated apatite than on
      hydroxyapatite, probably owing to environments with labile nonapatitic CO3(2-)
      and HPO4(2-) groups, along with a higher specific surface area which gives the CA
      a higher surface reactivity. These environments can be exchanged very rapidly,
      leading to the release of bFGF. The controlled release of adsorbed growth factor
      from carbonated apatite could provide means of improving bone healing in the
      future.

PMID- 9659611
TI  - Cellular ingrowth and thickness changes in poly-L-lactide and polyglycolide
      matrices implanted subcutaneously in the rat.
AB  - Highly porous matrices of poly-L-lactide (PL) and polyglycolide (PG), 24, 50, or
      95 mg/cc in the form of 10 x 10 x 3 mm wafers, were implanted subcutaneously (two
      per rat) in the flanks of 8-12-week-old female Lewis rats (n = 120). Matrices
      were harvested, two rats per week, for 15 weeks and examined histologically. At
      weeks 1 and 2, a thin fibrous capsule was present and matrices showed capillary
      beds and host-cell infiltration along the implant margins. By week 4, the PL
      specimens had some arterioles while the PG specimens still had only capillary
      beds. At week 7, PL had well developed arterioles, venules, and capillaries while
      PG began to show modest vascular beds of capillaries only. In terms of cellular
      ingrowth, PL remained unchanged from 7 to 15 weeks. Giant cell formation was
      observed wherever polymer was present. There was a loss of thickness and cell
      mass for both matrices over time (PG > PL) despite initial host-cell ingrowth. As
      both polymers degraded and were absorbed, the ingrown cells mass regressed. There
      was little remaining PG at 15 weeks, leaving no trace of cells that previously
      had ingrown and no evidence of scar tissue.

PMID- 9659613
TI  - Growth of human osteoblast-like cells on alkanethiol on gold self-assembled
      monolayers: the effect of surface chemistry.
AB  - Primary human osteoblasts were cultured on self-assembled monolayers (SAMs) of
      alkylthiols on gold with carboxylic acid and methyl termini, and the kinetics of
      cell attachment and proliferation were measured. Over 90 min approximately twice
      as many cells attached to carboxylic-acid-terminated monolayers as attached to
      methyl-terminated monolayers. After 24 h the number of cells attached to
      carboxylic-acid-terminated monolayers was ten times that attached to the methyl
      terminated monolayers. Cell morphology and cytoskeletal actin organization also
      were found to be different. Osteoblasts were cultured on SAMs that were patterned
      by photolithographic techniques. Cells attached almost exclusively to carboxylic
      acid-functionalized areas of the patterned surfaces, leaving methyl
      functionalized regions bare. The patterns strongly influenced the morphology of
      the attached cells. After 24 h, cells were observed to bridge between carboxylic
      acid-terminated regions separated by 75 microns, methyl-terminated regions but
      not those separated by 150 microns methyl-terminated regions. After 6 days in
      culture osteoblasts formed multilayers on the carboxylic-acid-terminated regions
      of the pattern.

PMID- 9659612
TI  - Relative importance of surface wettability and charged functional groups on NIH
      3T3 fibroblast attachment, spreading, and cytoskeletal organization.
AB  - Understanding the relationships between material surface properties, adsorbed
      proteins, and cellular responses is essential to designing optimal material
      surfaces for implantation and tissue engineering. In this study, we have prepared
      model surfaces with different functional groups to provide a range of surface
      wettability and charge. The cellular responses of attachment, spreading, and
      cytoskeletal organization have been studied following preadsorption of these
      surfaces with dilute serum, specific serum proteins, and individual components of
      the extracellular matrix. When preadsorbed with dilute serum, cell attachment,
      spreading, and cytoskeletal organization were significantly greater on
      hydrophilic surfaces relative to hydrophobic surfaces. Among the hydrophilic
      surfaces, differences in charge and wettability influenced cell attachment but
      not cell area, shape, or cytoskeletal organization. Moderately hydrophilic
      surfaces (20-40 degree water contact angle) promoted the highest levels of cell
      attachment. Preadsorption of the model surfaces with bovine serum albumin (BSA)
      resulted in a pattern of cell attachment very similar to that observed following
      preadsorption with dilute serum, suggesting an important role for BSA in
      regulating cell attachment to biomaterials exposed to complex biological media.

PMID- 9659614
TI  - Comparative histological evaluation of new tyrosine-derived polymers and poly (L
      lactic acid) as a function of polymer degradation.
AB  - Previous studies demonstrated that poly(DTE carbonate) and poly (DTE adipate),
      two tyrosine-derived polymers, have suitable properties for use in biomedical
      applications. This study reports the evaluation of the in vivo tissue response to
      these polymers in comparison to poly(L-lactic acid) (PLLA). Typically, the
      biocompatibility of a material is determined through histological evaluations as
      a function of implantation time in a suitable animal model. However, due to
      changes that can occur in the tissue response at different stages of the
      degradation process, a fixed set of time points is not ideal for comparative
      evaluations of materials having different rates of degradation. Therefore the
      tissue response elicited by poly(DTE carbonate), poly(DTE adipate), and PLLA was
      evaluated as a function of molecular weight. This allowed the tissue response to
      be compared at corresponding stages of degradation. Poly(DTE adipate)
      consistently elicited the mildest tissue response, as judged by the width and
      lack of cellularity of the fibrous capsule formed around the implant. The tissue
      response to poly(DTE carbonate) was mild throughout the 570 day study. However,
      the response to PLLA fluctuated as a function of the degree of degradation,
      exhibiting an increase in the intensity of inflammation as the implant began to
      lose mass. At the completion of the study, tissue ingrowth into the degrading and
      disintegrating poly(DTE adipate) implant was evident while no comparative
      ingrowth of tissue was seen for PLLA. The similarity of the in vivo and in vitro
      degradation rates of each polymer confirmed the absence of enzymatic involvement
      in the degradation process. A comparison of molecular weight retention, water
      uptake, and mass loss in vivo with two commonly used in vitro systems [phosphate
      buffered saline (PBS) and simulated body fluid (SBF)] demonstrated that for the
      two tyrosine-derived polymers the in vivo results were equally well simulated in
      vitro with PBS and SBF. However, for PLLA the in vivo results were better
      simulated in vitro using PBS.

PMID- 9659615
TI  - Fluorescent microplate assay for respiratory burst of PMNs challenged in vitro
      with orthopedic metals.
AB  - This report describes a simple, rapid, automated microassay for measuring in
      vitro changes of oxidative burst of phagocytes following challenge with metals
      for orthopedic devices. The production of reactive oxygen species (ROS) by
      polymorphonuclear leukocytes (PMNs) was measured using 2',7'-dichlorofluorescin
      diacetate (DCFH-DA) as fluorescent probe. DCFH-DA enters the cells and is
      oxidized by ROS to fluorescent DCF. The DCF generated was directly proportional
      to ROS produced intracellularly: The fluorescence intensity was read and
      converted to an index of ROS production by cells. In our experimental system,
      granulocytes (PMNs) were isolated from normal human blood and seeded in
      microplates. To verify if metals could influence ROS production, chromium,
      cobalt, nickel, molybdenum, titanium, aluminum, and vanadium prepared as aqueous
      extracts in phosphate-buffered saline were tested onto PMNs using
      phorbolmyristate acetate (PMA) as positive control. Molybdenum, aluminum, and
      vanadium increased ROS generation by PMNs, while signals not different from
      unstimulated PMNs were recorded for chromium, cobalt, nickel, and titanium. The
      DCFH-DA microplate-based assay provides an in vitro tool for the detection of
      oxygen-reactive species generated by PMNs as a response to metals.

PMID- 9659616
TI  - Atomic force microscopy used for the surface characterization of microcapsule
      immunoisolation devices.
AB  - The surface morphology of the microcapsule used as a bioartificial pancreas was
      examined by atomic force microscopy (AFM) under ambient conditions in a liquid
      environment. The standard contact mode was used for imaging. The capsules
      exhibited different morphologies and surface roughness depending on the
      composition of the cation solution: namely, the mole ratio of antigelling and
      gelling cations [Na+]/[Ca2+]. Surface roughness parameters obtained by AFM
      measurements provide quantitative information on the surface properties of the
      capsular membrane. In this respect, AFM can be considered a valuable technique
      complementary to optical microscopy in providing feedback for capsule
      optimization.

PMID- 9659617
TI  - The effects of cobalt chromium upon macrophages.
AB  - The purpose of this study was to elucidate the mechanisms by which cobalt
      chromium particulate wear debris contribute to the aseptic loosening of total
      joint prostheses. Incubation of macrophages with cobalt chromium led to release
      of tumor necrosis factor-alpha (TNF-alpha) and prostaglandin E2 (PGE2), but did
      not lead to release of interleukin-1 beta (IL-1 beta) or interleukin 6 (IL-6).
      Exposure of macrophages cocultured with osteoblasts to cobalt chromium also led
      to significant release of TNF-alpha and PGE2, but did not lead to significant IL
      6 or IL-1 beta production. The release of PGE2 in the coculture system was
      greater than that detected when macrophages were exposed to cobalt chromium
      without the osteoblast contribution. Exposure of radiolabeled calvaria to media
      from macrophages incubated with cobalt chromium in coculture with osteoblasts led
      to release of 45Ca. In contrast, exposure of radiolabeled calvaria to media from
      isolated macrophages incubated with these particles did not result in release of
      45Ca. Exposure of macrophages to cobalt chromium was toxic, as reflected by
      release of the intracellular enzyme lactate dehydrogenase. Macrophages play a
      role in the initiation of bone resorption at the interface through the
      phagocytosis of cobalt chromium particles and subsequent release of TNF-alpha and
      PGE2. The presence of osteoblasts at the interface may be required for
      amplification of the inflammatory response and ultimately for bone resorption.

PMID- 9659618
TI  - Cytotoxicity of 35 dental resin composite monomers/additives in permanent 3T3 and
      three human primary fibroblast cultures.
AB  - It was the purpose of this investigation to determine the cytotoxic effects (ED50
      concentrations) of 35 monomers or additives identified in commercial dental resin
      composites. Monolayers of permanent 3T3 cells and three primary human fibroblast
      types derived from oral tissues (gingiva, pulp, and periodontal ligament) were
      used as test systems. All substances were tested in concentrations ranging from
      0.01 to 5.0 mM. In general, ED50 values varied from 0.06 to > 5 mM. Within the
      groups of co(monomers), initiators, and cointiators, severe (e.g., Bis-GMA, UDMA,
      DMBZ, and DMDTA) or moderate (HEMA, BEMA, CQ, DMPT, and DMAPE) cytotoxic effects
      could be evaluated. Within the group of reaction/decomposition products, only
      moderate or slight effects were found (ED50: 0.7 to > 5 mM). The inhibitor BHT,
      the contaminant TPSb, and the photostabilizer HMBP, however, were highly
      cytotoxic in all cell cultures. In addition, the ED50 values of DBPO and HMBP
      significantly varied (0.43-3.8 mM, respectively, and 0.44-3.07 mM) with the
      applied cell culture. Our comprehensive screening shows that for several of the
      highly cytotoxic composite components, less cytotoxic alternatives are available.
      Furthermore, there was no cell type identified which was consistently less or
      more sensitive to the toxic effects of the tested compounds than the others.
      Primary human periodontal ligament and pulp fibroblasts, however, were found to
      be more sensitive than 3T3 and gingival fibroblasts to alterations from most
      tested substances.

PMID- 9659619
TI  - In vivo biocompatibility evaluation of nickel-titanium shape memory metal alloy:
      muscle and perineural tissue responses and encapsule membrane thickness.
AB  - Nickel-titanium shape memory alloy (Nitinol) has properties that could be very
      useful in surgical applications. Thermal shape memory, superelasticity, and high
      damping properties make such alloys behave differently compared to other implant
      metals. There has previously been a lack of sufficient evidence on the
      biocompatibility of Nitinol. The purpose of this study was to evaluate general
      soft tissue response and biocompatibility to Nitinol in vivo, and to clarify
      neural and perineural responses, previously unreported. Seventy-five rats were
      randomized into three groups. Test specimens were implanted into paravertebral
      muscle and near the sciatic nerve. A comparison was made between Nitinol,
      stainless steel, and Ti-6Al-4V. The animals were euthanized at 2, 4, 8, 12, and
      26 weeks after implantation. General morphologic and histologic observations were
      made under light microscopy. Semiautomatic computerized image analysis was used
      to measure the encapsule membrane thickness around the implants. The muscular
      tissue response to Nitinol was clearly nontoxic, regardless of the time period.
      The overall inflammatory response to Nitinol was very similar to that of
      stainless steel and Ti-6Al-4V alloy. There were no necroses, granulomas, or signs
      of dystrophic soft tissue clacification. The immune cell response to Nitinol
      remained low. Only a few foreign-body giant cells were present. The detected
      neural and perineural responses were also clearly nontoxic and nonirritating with
      Nitinol. No qualitative differences in histology between the different test
      materials could be seen. At 8 weeks, the encapsule membrane of Nitinol was
      thicker than that of stainless steel (mean 62 +/- 25 microns vs. 41 +/- 8
      microns). At the end of the study, the encapsule thickness was equal to all the
      materials tested. We concluded that Nitinol had good in vivo biocompatibility
      after intramuscular and perineural implantation in rats in the 26-week follow-up.
      Based on the results of the present study, Nitinol appears to have good potential
      for clinical use.

PMID- 9659620
TI  - Prostaglandins mediate the effects of titanium surface roughness on MG63
      osteoblast-like cells and alter cell responsiveness to 1 alpha,25-(OH)2D3.
AB  - Surface roughness affects proliferation, differentiation (alkaline phosphatase
      and osteocalcin), local factor production (transforming growth factor (TGF beta)
      and prostaglandin E2 (PGE2)], and response to 1,25-(OH)2D3 (1,25) of MG63
      osteoblast-like cells. In this study, we examined whether the effect of surface
      roughness on MG63 cells is mediated by prostaglandins produced by the cells.
      Unalloyed titanium (Ti) disks were pretreated with HF/HNO3 (PT) and then machined
      and acid-etched (MA). Disks were also coarse grit-sandblasted (SB), coarse grit
      sandblasted and acid-etched (CA), or plasma-sprayed with Ti particles (PS). The
      surfaces, from smoothest to roughest, were PT, MA, CA, SB, and PS. MG63 cells
      were cultured to confluence on the Ti disks in the presence or absence of 10(-7)
      M indomethacin (Indo), a specific inhibitor of cyclooxygenase activity, resulting
      in decreased prostaglandin production. When the cells reached confluence, cell
      number, cell layer alkaline phosphatase specific activity (ALPase), and
      osteocalcin (OC) and latent TGF beta (LTGF beta) production were determined. In
      addition, confluent cultures which had been grown in the absence of Indo were
      exposed to 10(-7) M 1,25, 10(-7) M Indo, or a combination of the two for 24 h. On
      the rougher surfaces, cell number was decreased and ALPase, OC, and LTGF beta
      were increased. When indomethacin was present throughout the culture period, the
      effect of surface roughness on cell number, OC, and LTGF beta was abolished.
      ALPase was reduced, but surface roughness-dependent effects were still observed.
      Addition of indomethacin to confluent cultures for 24 h had no effect on any of
      the parameters examined, with one exception: Cells cultured on MA surfaces
      exhibited a more differentiated phenotype. 1,25 increased all parameters examined
      on SB, CA, and PS surfaces. When indomethacin was added with 1,25, the 1,25
      dependent effects on cell number and OC and LTGF beta production were abolished;
      however, ALPase was unaffected. This indicates that bone cell response to
      systemic hormones may be modified by implant surface roughness. This effect may
      be mediated, at least in part, by prostaglandins produced by the same cells.

PMID- 9659621
TI  - Nitric oxide release by macrophages in response to particulate wear debris.
AB  - At the interface between a prosthetic implant and bone, macrophage interaction
      with particulate wear debris is a key event in the initiation of localized bone
      resorption, leading to aseptic loosening of the prostheses. Numerous
      investigators have reported that macrophages release a variety of cytokines and
      mediators including tumor necrosis factor, interleukin-1, prostaglandin E2, and
      interleukin-6 when they are stimulated with particulate wear debris. In this
      study, we have demonstrated that macrophages stimulated with particulate debris
      are also capable of releasing in copious amounts a key inflammatory chemical,
      nitric oxide. This release of nitric oxide was dependent upon the period of
      culture and the type and dosage of the challenging particles. Titanium-alloy
      particles were the most stimulatory, followed by commercially pure titanium and
      polymethyl-methacrylate. While the role of nitric oxide in osteolysis is not
      clearly understood, the literature suggests that it may be a key mediator in
      inhibiting DNA synthesis, in cell proliferation, and in stimulating PGE2 release.
      This finding enhances our understanding of the sequence of events occurring at
      the bone-implant interface during wear debris-mediated osteolysis, and exposes
      potential avenues to interrupt this sequence.

PMID- 9659622
TI  - Calcium phosphate induction by sol-gel-derived titania coatings on titanium
      substrates in vitro.
AB  - Titanium and its alloys are used widely in the manufacture of orthopedic and
      dental implants. Sol-gel-prepared titania is able to stimulate bone-like apatite
      formation in in vitro and in vivo cultures. These materials can be used, for
      example, as coatings on dental and orthopedic implants. However, the processes
      that lead to apatite formation are not fully understood. In this study different
      kinds of titania coatings on commercially pure titanium (c.p. Ti) were tested for
      apatite-forming ability. The rate of apatite formation is considered to be
      descriptive of a material's bioactive (bone-bonding) potential. Apatite-forming
      tests were done in simulated body fluid (SBF). Apatite-forming ability was
      highest with the addition of valeric acid to sol (600 degrees C) or with
      sintering sol-gel coatings at 450 degrees-550 degrees C. At that temperature
      range calcium phosphate forms on the coatings in 1 week. Calcium phosphate
      forming is observed in 1 day on standard coatings sintered at 500 degrees C.

PMID- 9659623
TI  - Radiotherapy residents' knowledge of and attitudes toward management of cancer
      pain.
AB  - PURPOSE: To evaluate the fund of knowledge of and attitudes toward cancer pain
      management of radiotherapy residents across the nation. METHODS: Radiotherapy
      (XRT) residents who had completed at least a year of training were surveyed by
      questionnaire. Residents (n = 10) from a training program who had been given
      instructional resources in cancer pain management skills were compared with
      residents from across the nation (n = 61). A validated survey used in national
      Cancer Pain Initiative Role Model Programs was administered by mail. The survey
      contained 30 questions that evaluated attitude alone (A), knowledge alone (K),
      and how attitude affects the application of knowledge (A/K). RESULTS: The
      residents from the training program scored significantly higher in K (p < 0.005)
      and A/K (p < 0.04) than did the residents across the nation. No difference in
      scores evaluating A were detected (p = 0.26). Compared with the baseline
      knowledge of physicians in practice who had attended a workshop on cancer pain
      management, the national XRT residents had significantly lower scores in A (p <
      0.006) and K (p < 0.001); however, no difference was found in A/K scores. After
      the workshop, the physicians in practice had significant gains in cancer pain
      management skills (p < 0.006). When the post-instruction survey was compared with
      the national XRT resident scores, there were marked differences in A (p <
      0.00001), K (p < 0.00001) and A/K (p < 0.01). CONCLUSIONS: XRT residents in the
      United States are empathetic, but knowledge of cancer pain management is lacking.
      Instruction in the principles of cancer pain management can make a profound
      difference in knowledge and attitude. There is a need to recognize cancer pain
      management as a significant aspect of radiotherapeutic practice.

PMID- 9659624
TI  - Information preferences, reading ability, and emotional changes in outpatients
      during the process of obtaining informed consent for autologous bone-marrow
      transplantation.
AB  - BACKGROUND: The complexity of autologous bone marrow transplantation (ABMT)
      imposes increased demands for disclosure of information to patients. This study
      describes the information preferences, reading ability, and emotional balance
      (affect) of adult patients at the time of outpatient informed consent. METHODS:
      Thirty patients were enrolled. The Derogatis Affects Balance Scale was used to
      determine each patient's emotional status before and after outpatient informed
      consent. The Information Styles Questionnaire was used to measure information
      preferences, and the Wide Range Achievement Test was used to measure reading
      ability. RESULTS: Every patient had at least average reading ability. Almost 90%
      of the patients preferred maximum amounts of detailed information. A significant
      change in total affectivity was seen after informed consent (p = 0.005), and the
      predominant pattern of change was decreases in both positive and negative
      affects, with a significant improvement in the positive-affects ratio.
      CONCLUSION: ABMT candidates tend to read well and prefer maximum amounts of
      information. The informed consent process is associated with significant change
      in the balance between positive and negative patient emotions, and the dominant
      pattern is neutralization of both the positive and the negative emotions. This
      neutralization is more pronounced for the negative emotions, suggesting that the
      informed consent process may make patients feel better overall.

PMID- 9659625
TI  - Promoting nurses' positive attitudes toward cancer prevention/screening.
AB  - BACKGROUND: From 1991 to 1994, a special projects grant to teach nurses cancer
      prevention/screening theory and clinical skills was developed, implemented, and
      evaluated. Approximately 60 nurses in Colorado rural settings attended five two
      day training sessions over a 20-month period. Attitudes, constructive or
      destructive, regarding specific behaviors lead to intentions to perform those
      behaviors and have an important impact on cancer-related nursing practice.
      METHODS: Two cancer-related attitude scales, Cancer Prevention/Early Detection
      Attitude Inventory and Fanslow Cancer Attitudes Scale, were administered prior to
      the first training session, following the final session, and at six-month follow
      up. Data reflecting program impact on nursing practice were obtained from follow
      up self-assessment of confidence in implementing new knowledge and skills.
      RESULTS: Significant differences in pre- and post-training attitude scores and
      fairly high-level confidence ratings suggest that these nurses will continue to
      use their cancer prevention and detection skills in practice. CONCLUSION:
      Documentation of practice activities to date has been impressive.

PMID- 9659626
TI  - The use of exfoliative cytology for the early diagnosis of oral cancers: is there
      a role for it in education and private practice?
AB  - BACKGROUND: Early detection of oral cancers is not easy, because oral
      precancerous lesions and early oral cancers can mimic many benign conditions in
      the mouth, leading to delays in diagnosis and treatment. There is a need to
      emphasize the early diagnosis of oral cancers in order to reduce the unacceptably
      high morbidity and mortality. METHODS: A survey regarding oral exfoliative
      cytology was completed by 132 dentists in Virginia who were randomly chosen from
      a mailing list. RESULTS: Less than half of the dentists (41.7%) had been taught
      how to obtain a cytologic smear, and only 26.0% knew the clinical indications for
      doing so. Only 9.2% of the dentists had ever obtained a cytologic smear in
      private practice. Of the 13 dentists in the survey who had done so, 12 had been
      trained in the technique. Interest in learning the cytologic technique and
      getting the needed supplies was indicated by 79.2% of the dentists. CONCLUSIONS:
      Diagnostic aids in the evaluation of oral mucosal lesions can serve an important
      role by identifying lesions that need to be biopsied in spite of a "benign"
      appearance. Exfoliative cytology, as well as vital staining, may aid in this
      goal. This has implications regarding undergraduate and postdoctoral education.

PMID- 9659627
TI  - An assessment of oral cancer prevention curricula in U.S. medical schools.
AB  - BACKGROUND: Oral cancer is readily detectable through routine examination, but
      five-year survival rates remain low. Physicians bear the same responsibilities as
      dentists in the early detection of oral cancers, because high-risk patients
      utilize medical services more often than dental services. METHODS: Because
      physicians' practices are largely influenced by their training, this study
      assessed the level of oral cancer education provided to undergraduate U.S.
      medical students. Health history and physical diagnosis course curricula were
      assessed for relevant content. RESULTS: The response rate from the U.S. medical
      schools was 63.2%. When compared with the "gold standard," the average score was
      43% of the optimum. Seven percent of the schools did not require inspection of
      the mouth, 29% required inspection of all oral structures, and intraoral
      palpation was advocated by 43% of the schools. Although most schools included
      questions about alcohol and tobacco use, only 13% asked about sunlight exposure.
      CONCLUSION: Preliminary oral cancer training in medical schools regarding
      physical assessment and elicitation of signs, symptoms, and high-risk behaviors
      lacks both adequacy and comprehensiveness.

PMID- 9659628
TI  - Mammography use among women attending an inner-city clinic.
AB  - BACKGROUND: Low-income, minority, and inner city women have breast cancer
      screening rates that are below those of the general population. METHODS: The
      authors surveyed women who received primary care at Seattle's county hospital
      about their mammography behaviors in early 1995. Data were analyzed within the
      context of the PRECEDE framework. RESULTS: Only half (48%) of the women were
      obtaining regular screening. Breast cancer and mammography beliefs differed by
      racial group. The following factors differentiated between inner-city women who
      were and were not regular users: mammography beliefs concerning early detection
      of disease, pressure from the machine causing breast cancer, and cost (these were
      less important among white women than members of other racial groups); previous
      physician discussions, concerns about appointment scheduling, and transportation
      problems; and social support from physicians, family, and friends. CONCLUSION:
      Interventions to encourage regular screening among inner-city women should
      address predisposing, enabling, and reinforcing factors.

PMID- 9659629
TI  - Characteristics of underserved women who did and those who did not use a free/low
      cost voucher as part of a mammography screening program.
AB  - BACKGROUND: Several programs have been designed to improve mammography screening
      participation in high-risk populations. The purpose of this cross-sectional study
      was to assess factors related to participation in a low-cost mammography
      screening voucher program. METHODS: The methods involved mailing a standardized
      survey to 101 participants in a low-cost mammography screening voucher program.
      The survey was designed to yield responses about the use of free mammography
      vouchers, women's knowledge of breast cancer, their perceptions of their risk of
      getting the disease, the usefulness of mammography and breast self-examinations,
      their information-seeking patterns, and general demographic information. RESULTS:
      Though knowledge and perceptions did not differ significantly between those who
      did and did not use the vouchers, voucher users were significantly older (47
      versus 40) and were more likely to have established patterns of previous
      mammography use. CONCLUSION: Voucher programs can influence women to obtain
      mammography, though probably not those at greatest risk of non-adherence.

PMID- 9659630
TI  - Strategies to encourage mammography use among women in senior citizens' housing
      facilities.
AB  - BACKGROUND: This randomized trial evaluated the impact of mammography-enhancing
      interventions implemented in 40 senior citizens' housing facilities in
      Pennsylvania and North Carolina. METHODS: After stratification of the facilities
      according to the socioeconomic status and racial backgrounds of their residents,
      they were randomly assigned to one of four groups to receive the following: 1)
      standard care--a Medicare mammography benefit flier; 2) education--the flier and
      a community education program; 3) access--the flier, mammography appointments,
      and transportation; 4) combined--all interventions. Telephone surveys, conducted
      prior to any intervention, identified mammography-eligible women, who were re
      surveyed six months later to ascertain mammography use. RESULTS: Logistic
      regression analyses identified mammography intention, age, and the interaction
      between ever having had mammography and being in the combined intervention group
      to be significant predictors of mammography use at six months. However, no
      significant main effect was found for any of the interventions. CONCLUSIONS:
      These results suggest that the combination of community-directed mammography
      education and access to mammography appointments encourages mammography use
      primarily by women who are already predisposed to having mammography. However,
      individually targeted and tailored interventions may be needed to encourage
      mammography use among women who have never had mammography and/or express no
      intention of having it done.

PMID- 9659631
TI  - The development of a Family Caregiver Cancer Education Program.
AB  - BACKGROUND: Recent years have seen an escalating trend toward early discharge of
      hospital patients, resulting in increasing numbers of patients being cared for at
      home by family members. Fear and anxiety concerning the well-being of the
      patient, the inability to provide adequate care, the cost of cancer treatment,
      and the anticipation of emotional stress are major factors that can contribute to
      the difficulty of this transition. METHODS: The Family Caregivers Cancer
      Education Program has been funded by the Pennsylvania Department of Health,
      Cancer Control Program to address these issues. This program encompasses
      education and support for caregivers as well as the Local Instructor Course to
      provide nurse and social worker teams with materials, information, and support to
      offer the caregiver course within their areas. Focus groups were conducted to
      determine course content. RESULTS AND CONCLUSIONS: Participant evaluations
      demonstrate that caregivers who attend the course feel less overwhelmed and
      better able to cope with the caregiver experience.

PMID- 9659632
TI  - Medicine and ancient Mexico: Rivera's view.

PMID- 9659633
TI  - Chronic cannulation and fistulization procedures in swine: a review and
      recommendations.
AB  - Swine are important animal models in biomedical research. Some experimental
      procedures may require chronic access to blood vessels, organs, and structures.
      Chronic access procedures may be utilized for collection of blood and body fluids
      as well as for the infusion of test substances. This manuscript reviews
      methodologies that have been reported to be effective for these procedures. It
      also makes recommendations on the maintenance of indwelling catheters, cannulas,
      and fistulas.

PMID- 9659634
TI  - The effect of subcutaneous edema on transcutaneous oximetry.
AB  - A rabbit animal model of tissue edema was created to determine its effect on
      transcutaneous oximetry (T-com). Measurements of T-coms were performed before and
      at 5-minute intervals after the injection of body temperature saline into the
      skin and subcutaneous tissues of 5 rabbits. Photomicrographs were obtained to
      document the morphological appearance of edema. The injection of saline had no
      effect on relative T-com values. This investigation suggests that edema alone
      does not influence T-com measurements.

PMID- 9659635
TI  - A mechanical and histomorphometric analysis of bone bonding by hydroxyapatite
      coated strain gages.
AB  - Identification of the strains controlling bone remodeling is important for
      determining ways to prevent bone loss due to load deprivation, or implant
      placement. Long-term monitoring of strains can potentially provide the best
      information. Glues are resorbed within 2-3 weeks. Two formulations of
      microcrystalline hydroxyapatite (HA) were used to attach strain gages to rat
      femora to assess their long-term in vivo strain measurement capability. Seven
      male rats received HA-coated gages, and 2 animals underwent a sham procedure. The
      gages were prepared using a published technique and placed on the antero-lateral
      aspect of the left femora. After 6-7 weeks, the animals were euthanized and both
      femora explanted. Gages were attached to the right femora with cyanoacrylate. All
      femora were tested in cantilever bending, then embedded, sectioned, and stained
      with mineralized bone stain. The undecalcified sections were examined using
      transmitted and ultraviolet light microscopy. Mechanical testing showed one HA
      formulation provided 70-100% bonding. Histology showed intimate contact between
      the gage and bone surface. Histomorphometry indicated increased bone activity
      under the gage compared to the remaining bone, the controls, and the shams. The
      results indicate that microcrystalline HAs bond to bone quickly and can allow
      long term in vivo measurements.

PMID- 9659636
TI  - Organ preservation with EC, HTK, and UW solutions in orthotopic liver
      transplantation in syngeneic rats. Part I: Functional parameters.
AB  - Ischemic injury to the liver is known to influence the outcome of liver
      transplantation. In this study the efficacy of Euro-Collins (EC), histidine
      tryptophan-ketoglutarate (HTK), and University of Wisconsin (UW) preservation
      solution was analyzed in the model of orthotopic liver transplantation in
      syngeneic rats. The study design was as follows: Group I, Euro-Collins solution
      (n = 11); Group II, Histidine-Tryptophan-Ketoglutarate solution (n = 11); Group
      III, University of Wisconsin solution (n = 11). The rat liver transplantation was
      performed with arterialization of the graft as described by Engemann. The
      postoperative follow-up was 28 days. The perfusion flow rate of the preservation
      solution measured during organ perfusion revealed lowest levels in the UW group
      and comparable levels in Groups I and II. Postoperative graft function was
      monitored by measuring liver enzymes (aspartate amino-transferase, ASAT, alanine
      aminotransferase, ALAT), bilirubin and bile production. The survival rate was
      10/11 in each group. Liver enzymes and bilirubin increased postoperatively and
      went back to normal within 2 or 3 weeks. In contrast to bilirubin, the liver
      enzymes showed a biphasic increase with maxima on the 1st and 5th days (range:
      ALAT, 220-264 U/L; ASAT, 145-177 U/L). Bile production was observed in all
      groups, but was significantly higher after UW-preservation (P < .005). Analysis
      of inflammatory cells revealed high concentrations of intrasinusoidal leukocytes
      and lymphocytes in the graft with a maximum on the 5th day.

PMID- 9659637
TI  - Prolonged survival in fetal rabbit surgery.
AB  - Timing and outcome of antenatal surgical intervention is being explored using
      fetal animal models. Models that are currently used range from larger animals
      with fewer offspring and higher cost to smaller animals with larger litters and
      lower cost. The rabbit is an ideal "small" animal model for experimentation in
      the third trimester, with a large litter, short gestation and a relatively large
      fetus. This paper reports methods by which prolonged survival (greater than 110
      days) may be achieved in as many as 60% of operated fetuses following complex
      fetal surgery in the rabbit.

PMID- 9659638
TI  - Internal carotid artery dissection: an animal model?
AB  - This paper describes an internal carotid artery (ICA) dissection model in a
      rabbit. An animal model for ICA dissection has not been described. New Zealand
      White rabbits were anaesthetized and surgical microdissection performed to expose
      the right internal carotid artery. A small arteriotomy was performed and a
      subadventitial plane of dissection created using blunt dissection and injected
      heparinized saline. The adventitia was sutured and the animals were recovered
      after closure of the wound. The procedure was repeated on the left ICA after 7
      days with removal of the left ICA for control samples and removal of the right
      ICA to obtain sample specimens. The brain was also removed. A total of 11 control
      specimens and 9 sample specimens were obtained. The mean length of these
      specimens (n = 20) was 5.5 mm (range 5-6 mm). The mean length of dissection of
      the control specimens (n = 11) was 2.2 mm (range 2-3 mm). The mean length of
      dissection on sample specimens (n = 9) was 2 mm (range 1-3 mm). There was no
      extension of the arterial dissection. There was no intraluminal thrombosis or
      cerebral infarction. This model was able to induce arterial wall dissection in a
      rabbit. There was no extension of the induced dissection over 7 days. No local
      arterial or cerebral ischemic complications developed from the dissection.

PMID- 9659639
TI  - Subcutaneous ureteral replacement: a canine model.
AB  - There are several clinical situations in which extrinsic or intrinsic ureteral
      diseases necessitate extensive reconstructive surgery. Unfortunately, not all
      patients are candidates for such surgery (e.g., those with retroperitoneal
      metastatic disease). Ureteral replacement is indicated in this selected group of
      patients. A viable option is to establish a ureteral replacement using
      subcutaneous tubes. Among the problems associated with this method of urine
      diversion are selecting the proper material for the tubes, the timing of tube
      replacement, encrustation and occlusion, urine reflux, and renal function. There
      is an obvious need for an animal model to address these issues. The aim of this
      study was to establish a reproducible canine model for subcutaneous ureteral
      replacement, by using a combination of nephrostomy and cystostomy tubes joined
      together under the skin. The animal study was conducted in 6 dogs. A pigtail
      nephrostomy and a cystostomy were inserted through a midline abdominal incision
      and stab wounds in the abdominal wall. A subcutaneous tract was bluntly made
      toward the nephrostomy incision starting from the cystostomy incision. The
      nephrostomy was grasped with the clamp and brought through the subcutaneous
      tunnel to the cystostomy incision. Upon emerging through the cystostomy incision,
      the tubes were joined and buried under the skin. Intravenous urography at 4-6
      weeks postoperatively in 4 dogs showed no deterioration of renal function, but
      some hydronephrosis was present. Using the technique described in this paper, it
      is possible to establish a subcutaneous ureteral replacement using nephrostomy
      and cystostomy tubes in dogs. This model may serve for further research of the
      various questions associated with subcutaneous ureteral replacement in humans.

PMID- 9659640
TI  - Bipolar pacemaker leads: new materials, new technology.
AB  - This commentary is in response to a review published earlier in this journal. It
      is intended to provide additional information and supplement the original paper.
      A short review of the failure mechanisms of polyurethane pacing lead materials is
      provided. Two specific degradation mechanisms, environmental stress cracking and
      metal ion oxidation, are discussed. Environmental stress cracking has been
      extensively studied and is a well understood failure mechanism. Methods for
      reducing the problem have been developed and tested in vivo. As a result, stress
      cracking failures can be virtually eliminated. Metal ion oxidation failures now
      dominate pacing lead recalls. Two new materials, polycarbonate urethanes and
      ethylenetetrafluoroethylene, have been introduced as insulators for pacing leads.
      These materials do not fail by stress cracking and preliminary test results are
      very positive.

PMID- 9659641
TI  - Patient care or paper care?

PMID- 9659642
TI  - Survey of sleeping position after hospital discharge in healthy preterm infants.
AB  - OBJECTIVE: To evaluate the prevalence of nonprone (supine or side) versus prone
      sleeping position in healthy preterm infants. STUDY DESIGN: A questionnaire on
      sleeping position was mailed to mothers of 167 preterm infants discharged from
      the intermediate nursery at Packard Children's Hospital at Stanford. The
      prevalence of nonprone sleeping at 1 month (term corrected age) and 3 months (2
      months corrected age) after nursery discharge was analyzed by an unpaired t test.
      RESULTS: Nonprone position sleeping occurred in 64% initially and dropped to 35%
      at 2 months corrected age. CONCLUSIONS: Overall, nonprone sleeping was widespread
      in our healthy preterm infants after hospital discharge but may not persist. A
      majority of these infants were sleeping prone during a high-risk period for
      sudden infant death syndrome.

PMID- 9659643
TI  - Recombinant human erythropoietin therapy for treatment of anemia of prematurity
      in very low birth weight infants: a randomized, double-blind, placebo-controlled
      trial.
AB  - OBJECTIVE: To evaluate the efficacy and safety of recombinant human
      erythropoietin (rHuEPO) in very low birth weight infants with anemia of
      prematurity. STUDY DESIGN: Thirty infants were randomly assigned to receive
      either rHuEPO (300 U/kg per dose) or placebo twice a week. Hematologic
      parameters, transfusion requirements, caloric intake, and growth were monitored.
      RESULTS: The number and volume of erythrocyte transfusions were significantly
      lower in infants treated with rHuEPO. Serum ferritin levels, similar in both
      groups at study entry, fell and were significantly lower in rHuEPO-group infants
      at the completion of the study. An inverse correlation was observed between
      reticulocyte count and absolute neutrophil count both at entry and at completion
      of the study. CONCLUSION: Twice-a-week administration of rHuEPO significantly
      reduces the need for erythrocyte transfusion in very low birth weight infants in
      stable condition. A significant decrease in serum ferritin levels in infants
      receiving rHuEPO suggests the need to determine the optimal dose of iron
      supplementation in these infants.

PMID- 9659644
TI  - Perinatal outcomes in women with systemic lupus erythematosus.
AB  - OBJECTIVE: Pregnancies of women with systemic lupus erythematosus (SLE) were
      studied to assess the effects interaction of this disease and pregnancy. STUDY
      DESIGN: Charts of pregnant women with a discharge diagnosis of lupus were
      reviewed. Inclusion criterion was SLE diagnosed by the criteria of the American
      College of Rheumatology. All patients were cared for at the University of North
      Carolina Hospitals, a tertiary level university center. RESULTS: Between January
      1988 and June 1995, we participated in the care of 21 women with the diagnosis of
      SLE. Their obstetric histories included a total of 56 pregnancies spanning 19
      years. Obstetric histories were divided into pregnancies occurring before the
      patient was diagnosed with lupus and those pregnancies occurring after she had
      been given the diagnosis. The diagnosis of lupus was made during the course of
      five pregnancies; those five were categorized as occurring after diagnosis. Of
      the pregnancies that occurred before a woman's diagnosis of SLE, 46% resulted in
      live births, 36% ended in spontaneous abortion, and 18% ended in an intrauterine
      fetal demise. Among pregnancies occurring after the diagnosis of SLE, 85%
      resulted in live birth, 10% in spontaneous abortion, 3.3% in intrauterine fetal
      demise, and 3.3% in neonatal death. Of all live births, 53% were delivered before
      37 weeks' gestation. The most common causes of maternal morbidity were joint
      involvement (n = 8) and dermatologic disorders (n = 6). Other clinical
      manifestations of SLE included nephritis (n = 5), hypertension (n = 4), pleuritis
      (n = 3), and thrombocytopenia (n = 3). One maternal death occurred as a result of
      pulmonary disease. Four pregnancies were complicated by preeclampsia. Seven
      patients were hospitalized during their pregnancies for lupus-related
      complications. CONCLUSIONS: Substantial fetal, neonatal, and maternal risks still
      exist for pregnant women with lupus.

PMID- 9659645
TI  - Intrauterine cocaine and crack exposure: neonatal outcome.
AB  - OBJECTIVE: Adverse health effects are associated with intrauterine cocaine
      exposure. The purpose of this study was to investigate the impact of fetal
      cocaine and crack exposure on neonatal outcome. STUDY DESIGN: We enrolled 386
      mother-infant pairs, including 130 matched control pairs, in the study. The
      course of pregnancy and delivery was followed and neonatal outcome was assessed
      by physical and neurologic examination, as well as by the Brazelton Neonatal
      Behavioral Assessment Scale and the Neonatal Stress Scale. RESULTS: The cocaine
      exposed neonates had significantly more adverse effects than the matched control
      infants. Birth weight, length, and head circumference were significantly lower in
      the cocaine- and crack-exposed infants (p < or = 0.001). There were significantly
      more premature infants (p < or = 0.007) in this group. They demonstrated
      significant abnormalities on the neurologic examination (p < or = 0.001),
      inferior performance on the Brazelton Neonatal Behavioral Assessment Scale (p <
      or = 0.001), and higher scores on the Neonatal Stress Scale (p < or = 0.001).
      Predictors of negative neonatal outcome were maternal age (p < or = 0.02), poor
      paternal relationship with the mother (p < or = 0.002), crack use (p < or =
      0.004), cocaine use (p < or = 0.009), and marijuana use (p < or = 0.05).
      CONCLUSION: The single most important predictor of neonatal outcome is the
      frequency, quantity, and type of cocaine used.

PMID- 9659646
TI  - Transcutaneous measurement of carbon dioxide tension during long-distance
      transport of neonates receiving mechanical ventilation.
AB  - OBJECTIVE: To determine the efficacy of transcutaneous carbon dioxide tension
      measurement during high-risk neonatal transport. STUDY DESIGN: This was a
      prospective, randomized comparative study. Infants transported from hospitals
      more than 30 miles away from our center and who required respiratory intervention
      were enrolled. Alternating transports used a transcutaneous CO2/O2 monitor.
      Ventilation parameters and end transport blood gas values served as primary
      endpoints for the study. RESULTS: Infants with transcutaneous carbon dioxide
      tension monitoring were more likely to have decreased ventilator peak pressures
      during transport than neonates not monitored (-1.5 cm H2O vs + 0.6 cm H2O; p =
      0.04). Monitored neonates were more likely to arrive at the tertiary center with
      a more normal pH and a CO2 tension between 35 and 45 mm Hg (4.7 to 6.0 kPa) than
      nonmonitored infants (p = 0.03 and p = 0.01, respectively). The stabilization
      times before transport were not significantly prolonged by the use of the
      transcutaneous monitor. CONCLUSIONS: Transcutaneous monitoring of CO2 tension
      improves short-term respiratory outcome in neonates receiving mechanical
      ventilation during transport.

PMID- 9659647
TI  - Recurrent seizures in a neonate after lidocaine administration.
AB  - OBJECTIVE: We report recurrent seizures in a neonate after intravenous lidocaine
      administration at the recommended dose for intubation and supplementation of
      general anesthesia. STUDY DESIGN: Further evaluation of this case included
      determination of serum lidocaine level, serum electrolyte levels, and arterial
      blood gas values; cerebral spinal fluid analysis; an electroencephalogram; head
      ultrasonography; brain stem auditory evoked response testing; and a complete
      developmental evaluation. Previously published literature discussing lidocaine
      toxicity and pharmacokinetics is reviewed. RESULTS: The lidocaine level in the
      patient was 0.3 mg/L 2 hours after the last dose was administered. Results of the
      remaining studies were within normal limits, and the patient had no additional
      seizures several months after birth. CONCLUSION: We caution that lidocaine
      administration to newborn infants at previously accepted doses may result in life
      threatening side effects, including prolonged seizures.

PMID- 9659648
TI  - Obstetric and gynecologic implication of brucellosis in Kuwait.
AB  - OBJECTIVE: To study the possible correlation between maternal Brucella infection
      and reproductive failure as expressed by abortion, intrauterine fetal death, and
      preterm delivery. STUDY DESIGN: Maternal enzyme-linked immunosorbent assay
      serologic and microagglutination testing and conception product culture for
      Brucella were done in 227 women with preterm delivery, 51 with intrauterine fetal
      death, 29 with spontaneous abortion, and 39 with term delivery of a normal baby.
      RESULTS: Ingestion of raw milk was positive in 18% of the control cases, 28% of
      preterm delivery cases, 30% of intrauterine fetal death cases, and 21% of
      spontaneous abortion cases. Acute or chronic Brucella infection was found in 8%
      of preterm, 10% of intrauterine fetal death, and 7% of abortion cases. None of
      the control cases had evidence of Brucella infection. None of the four groups
      showed positive culture of the placenta for Brucella. The titres of Brucella
      specific immunoglobulin G and M were significantly higher in the preterm,
      abortion, and intrauterine fetal death groups than in the control group.
      CONCLUSION: A possible correlation may exist between Brucella infection and
      preterm and intrauterine fetal death, which does not seem to be related to
      transplacental infection but possibly may relate to the acute illness.

PMID- 9659649
TI  - Splenectomy for hairy cell leukemia in pregnancy.
AB  - OBJECTIVE: Hairy cell leukemia is a rare hematologic malignant disease
      characterized by pancytopenia and splenomegaly. Its occurrence during pregnancy
      limits treatment with standard chemotherapeutic agents. A woman was found to have
      hairy cell leukemia and massive splenomegaly late in the second trimester. A
      review of the literature did not provide a carefully formulated treatment plan.
      It was believed that splenectomy (the historic therapy for hairy cell leukemia)
      would likely result in improved hematologic values and allow the pregnancy to
      progress. STUDY DESIGN: Case report with literature review. RESULTS: Preoperative
      laboratory studies revealed platelet count 65,000/mm3, hematocrit 28.6%, white
      blood cell count 4000/mm3, and hairy cell index 0.06 to 0.07. At 24 weeks'
      gestation, the patient underwent splenectomy with resolution of thrombocytopenia
      and normal progression of pregnancy without complication. Repeat cesarean section
      at 38 weeks produced a 2875 gm healthy male infant with Apgar scores of 9 and 9.
      CONCLUSION: If antepartum management of hairy cell leukemia is warranted,
      splenectomy is a safe and effective treatment option during the second trimester.

PMID- 9659650
TI  - Double-blind, randomized comparison of the effect of carbetocin and oxytocin on
      intraoperative blood loss and uterine tone of patients undergoing cesarean
      section.
AB  - OBJECTIVES: A double-blind randomized study involving pregnant women undergoing
      cesarean section was conducted to compare the effectiveness of a single 100
      micrograms intravenous injection of the long-acting oxytocin analog, carbetocin,
      with that of a standard infusion of oxytocin with respect to intraoperative blood
      loss. The two treatments also were compared for safety and ability to maintain
      adequate uterine tone. STUDY DESIGN: The study drug was administered to 57 women
      during elective cesarean section after placental delivery; blood was collected
      until abdominal closure. Intraoperative blood loss was calculated with a
      sensitive colorimetric method. Position, tone of the fundus, and vital signs were
      assessed up to 24 hours after the operation. The need for additional uterotonic
      agents was recorded. RESULTS: A single 100 micrograms intravenous injection of
      carbetocin was as effective as a continuous 16 hour infusion of oxytocin in
      controlling intraoperative blood loss after placental delivery. Mean blood loss
      after carbetocin administration was 29 ml less than after oxytocin administration
      (p = 0.3). Subset analysis deleting two patients who received oxytocic
      intervention in the operating room and one extreme outlier revealed a mean blood
      loss of 41 ml less in the carbetocin group (p = 0.14) with lower variances (p =
      0.02). The percentage of patients with blood loss of 200 ml or less was greater
      with carbetocin (79% vs 53%; p = 0.041). Carbetocin enhanced early postpartum
      uterine involution. The fundus was below the umbilicus in more patients who
      received carbetocin at 0, 2, 3, and 24 hours on the ward (p < 0.05). There were
      no significant differences in uterine tone or type or amount of lochia.
      Additional oxytocin was used to treat three patients for postpartum hemorrhage or
      persistent uterine atony. All interventions were in the oxytocin group. Vital
      signs and hematologic values were comparable in each group, confirming similar
      safety profiles. CONCLUSIONS: A single 100 micrograms intravenous injection of
      carbetocin is as effective and more reliable than a standard continuous infusion
      of oxytocin in maintaining adequate uterine tone and preventing excessive
      intraoperative blood loss during cesarean section after delivery of the placenta.
      Patients receiving carbetocin required less intervention. Carbetocin was well
      tolerated.

PMID- 9659651
TI  - The route to empowerment: a mother's perspective.

PMID- 9659652
TI  - International Perinatology/Neonatology--a global perspective.

PMID- 9659653
TI  - Isopropyl pad use in neonatal intensive care units.
AB  - OBJECTIVES: Isopropyl pads (IPs) are commonly used to cleanse skin. This
      traditional practice is benign when applied to adults, however, its efficacy and
      safety when used for health-compromised neonates is questionable. This research
      explores the extent of IP use in 114 infants in neonatal intensive care units and
      identifies characteristics associated with IP use. STUDY DESIGN: A descriptive
      design, with data collected at two different sites over multiple observation
      periods, was used. RESULTS: Generally low IP to skin use was found, with most
      babies being exposed to one to two pads per 8 hours. Some babies, most frequently
      the lowest weight, most premature, and health compromised babies, had exposure to
      as many as eight pads per 8 hours. CONCLUSIONS: Because the smallest, most
      vulnerable neonates are those most exposed to the highest levels of isopropyl
      alcohol on the skin, conscious attention needs be paid to IP use to avoid or
      eliminate unnecessary exposure to the potentially toxic substance.

PMID- 9659654
TI  - Response to inhaled nitric oxide in persistent pulmonary hypertension of the
      newborn: relationship to baseline oxygenation.
AB  - OBJECTIVE: We hypothesized that the magnitude of response to inhaled nitric oxide
      in persistent pulmonary hypertension of the newborn would correlate with the
      degree of baseline hypoxemia. STUDY DESIGN: We performed a retrospective chart
      review of 15 consecutive newborn infants with persistent pulmonary hypertension
      of the newborn treated with inhaled nitric oxide as part of a pilot study.
      Oxygenation index was calculated for each patient at baseline and 0.5 and 24
      hours after the start of therapy and findings were compared by repeated-measures
      analysis of variance. Correlation was determined between baseline oxygenation
      index and 24-hour change in oxygenation index. RESULTS: Patients had a rapid and
      sustained decrease in oxygenation index (66.7 +/- 14.8 vs 26.3 +/- 5.0 vs 12.9 +/
      2.8, baseline vs 0.5 hour vs 24 hours; p < 0.001) during the study period, and
      the change in oxygenation index was highly correlated with baseline oxygenation
      index (r2 = 0.98). Two patients were placed on extracorporeal membrane
      oxygenation support before the 24-hour time point because of overwhelming sepsis
      and severe cardiac dysfunction. CONCLUSIONS: In patients with severe persistent
      pulmonary hypertension of the newborn, we conclude that the clinical response to
      inhaled nitric oxide is most dramatic in those patients with the most severe
      hypoxemia.

PMID- 9659655
TI  - Home blood pressure monitoring for pregnant patients with hypertension.
AB  - OBJECTIVE: To determine whether automated measurement of blood pressure and pulse
      in a home setting can be easily accomplished by pregnant women with chronic
      hypertension. STUDY DESIGN: In this prospective investigation, seven women with
      chronic hypertension complicating pregnancy recorded their blood pressure at home
      twice a day. These data were offloaded once daily into a computer at a remote
      site, and a computerized printout of these data was received by the physician.
      RESULTS: The patients participated in the study for 12.2 +/- 5.8 weeks (range 4
      to 18 weeks) and were between 23 and 42 weeks' gestation. Average mean arterial
      pressure in the home was 102 +/- 10 mm Hg, and average pulse was 81 +/- 11 beats
      per minute. In the clinic, the values were 112 +/- 13 mm Hg and 90 +/- 30 beats
      per minute (p < 0.05). Each patient was easily taught how to use the machine.
      CONCLUSIONS: The home blood pressure monitoring device was easy to use and
      correlated well with values recorded by health professionals for this limited
      number of subjects. It was particularly helpful to patients (n = 5) who lived
      long distances (more than 60 miles) from the clinic and to women who needed
      adjustments of antihypertensive medication.

PMID- 9659656
TI  - Improving the timing of antibiotic administration to high-risk newborns.
AB  - OBJECTIVES: To describe the timing of initiation of administration of parenteral
      antibiotics to infants with suspected sepsis at birth, identify barriers to
      prompt administration, and assess the effectiveness of subsequent interventions
      designed to minimize these barriers. The goals were to administer antibiotics
      within 1 hour of the physician order and within 2 hours of birth with more than
      80% compliance for both goals. STUDY DESIGN: Retrospective chart review and
      prospective interventions involved 488 infants born at the University of Michigan
      Medical Center with indications for antibiotic therapy at birth. After an initial
      audit of the charts of 56 infants and the identification of poor compliance with
      the goals, unit policies and educational programs were developed to facilitate
      timely antibiotic administration. After a second audit demonstrated improvement
      but failure to attain the target compliance rates, review of individual cases
      with the responsible physician and nurse was initiated. Time intervals between
      birth, writing the order for antibiotics, noting the order by the nurse, and
      administration of antibiotics were tracked for an additional 20 months after
      these interventions. RESULTS: Before the interventions, antibiotics were
      administered to 28% of infants within 1 hour of the physician order (mean +/- SEM
      1.58 +/- 0.11 hours) and to 19% within 2 hours of birth (3.12 +/- 0.16 hr). By
      the conclusion of the study, antibiotics were administered to 87% (p < 0.0001) of
      infants within 1 hour of the physician order (0.79 +/- 0.04 hour; p < 0.001) and
      to 92% (p < 0.0001) within 2 hours of birth (1.26 +/- 0.06 hours; p < 0.001).
      CONCLUSIONS: Administration of the first dose of parenteral antibiotics to
      newborns with suspected sepsis at birth frequently takes more than 1 hour after
      the order is written and more than 2 hours after birth. Efforts to identify and
      minimize common barriers significantly improved the timing of antibiotic
      administration. Additional improvement was attained by means of continued
      surveillance and individual feedback to caregivers of infants when timing
      objectives were not fulfilled.

PMID- 9659657
TI  - Congenital cytomegalovirus infection presenting as severe persistent pulmonary
      hypertension of the newborn.

PMID- 9659658
TI  - Umbilical cord blood gas casebook.

PMID- 9659659
TI  - Fetal heart rate monitoring casebook.

PMID- 9659660
TI  - Special imaging casebook.

PMID- 9659661
TI  - Enteric neuropathophysiology and inflammatory bowel disease.

PMID- 9659662
TI  - Structural abnormalities of the nervous system in Crohn's disease and ulcerative
      colitis.

PMID- 9659663
TI  - Luminal cross-sectional area and tension-strain relation of the porcine bile
      duct.
AB  - The bile duct is a distensible tube serving to transport bile from the liver and
      gallbladder to the duodenum. The purpose of this study was to characterize the
      luminal cross-sectional area (CSA) and tension-strain properties during
      distension of the normal isolated porcine common bile duct in vitro. An impedance
      planimetric system located inside a balloon was used. Eleven porcine bile ducts
      were examined in two locations, in the hepatic duct and in the common bile duct.
      The CSAs obtained in the common bile duct were significantly higher than those in
      the hepatic duct in the pressure range 0-8 kPa (P < 0.001). The circumferential
      wall tension (T)-strain (epsilon) relations for both locations fitted to the
      exponential equation T = a.eb. epsilon with determination coefficients of 0.97 +/
      0.01. The a and b constants were not statistically different between the two
      locations indicating that the elastic properties did not differ. In conclusion,
      the luminal CSAs were larger in the common bile duct when compared to the hepatic
      duct and the tension-strain relations did not differ between the two segments of
      the bile duct.

PMID- 9659664
TI  - Gastric myoelectrical and antroduodenal motor activity in patients with
      achalasia.
AB  - Achalasia is a primary motor disorder of the oesophagus, in which the myenteric
      plexus is involved. However, abnormalities in other parts of the digestive tract
      have also been described in achalasia. Whether gastric myoelectrical and duodenal
      motor activity in these patients is also affected is unknown. Therefore,
      interdigestive and postprandial gastric myoelectrical and antroduodenal motor
      activity were studied in 11 patients with achalasia, using electrogastrography
      (EGG) and stationary antroduodenal manometry. Electrogastrographically, no
      differences were found in the gastric frequency, incidence of dysrhythmias and
      postprandial/fasting power ratio. In the interdigestive state a lower propagation
      velocity of phase III episodes was found in the achalasia patients, but other
      parameters were unaltered. Postprandially, no differences were found in the
      number of pressure waves, in the amplitude of pressure waves or in antroduodenal
      coordination. We conclude that gastric myoelectrical activity and antral motor
      activity in patients with achalasia is normal, suggesting an intact extrinsic and
      intrinsic neural innervation of the distal stomach. Although postprandial
      duodenal motility is normal, a lower propagation velocity of phase III suggests
      involvement of the small intestine in achalasia.

PMID- 9659665
TI  - Discharge patterns of intramural mechanoreceptive afferents during selective
      distension of the cat's rectum.
AB  - The afferent input from the rectum to the central nervous system (CNS) has yet to
      be thoroughly characterized. The characteristics of mechanoreceptive rectal
      afferents have been studied in unanaesthetized decerebrate cats. Following lumbo
      sacral laminectomy, single-unit activity (occasionally multi-unit activity) was
      recorded from centrally cut filaments of the sacral dorsal roots (predominantly
      S2), while a balloon was inflated in the rectum. Starting from their background
      activities (mean 15.1 imp sec-1, SD 7.6 imp sec-1), afferent discharge rate
      increased with increasing balloon pressure (mean threshold 6.3 mmHg, SD 3.6
      mmHg). The dependence of firing rate on intrarectal pressure began to flatten out
      at 25 mmHg (mean; SD 10 mmHg). For 22 out of 29 units (76%) complete saturation
      occurred at 35 mmHg (mean; SD 15 mmHg) with a maximum discharge rate of 31 imp
      sec-1 (mean; SD 12.6 imp sec-1). In a number of recording sessions, cyclical
      rectal contractions were observed. In these cases, changes in firing of the units
      were closely related to changes in intrarectal pressure. Pressure-related
      afferent activity could be enhanced by parasympathomimetic drugs which augmented
      rectal contractions. We conclude that sacral dorsal roots contain afferents from
      low-threshold mechanoreceptors located in the rectal wall, and that these
      afferents monitor the filling state and contraction level of the rectum.

PMID- 9659666
TI  - Postprandial peristalsis in the human duodenum.
AB  - MMC-related retroperistalsis is a cyclical phenomenon in the duodenum linked to
      phase III. The aim of this study was to elucidate the direction of propagation of
      juxtapyloric duodenal pressure waves in the postprandial state in healthy humans
      and to compare with the contractions in the interdigestive phase II.
      Antroduodenal manometry was performed in 11 healthy subjects. Individual pressure
      waves propagating along a 6-cm duodenal segment were analysed with respect to the
      proportions of antegrade and retrograde propagation in the four duodenal
      subsegments (D1-D2) to (D4-D5), each subsegment being 15 mm. A test meal was
      given 30 min after a phase III had passed and motility recording continued for 60
      min after the meal. During both the first and the second 30-min period of
      postprandial recording the proportion of retrograde pressure waves was larger
      just distal to the pylorus, (D1-D2), 40% (23-68) and 50% (23-68), respectively,
      compared to the distal part, (D4-D5), of the duodenal segment, 29% (12-30) and
      10% (10-24), respectively (P < 0.05 and 0.01). In contrast, during late phase II
      of the interdigestive state antegrade pressure waves predominated in all four
      duodenal subsegments. We conclude that in the postprandial state a high
      proportion of the duodenal pressure waves (40-50%) is retrograde in the immediate
      juxtapyloric area while antegrade contractions predominate at a distance 5-6 cm
      distal to the pylorus. These manometric data together with recent observations of
      postprandial transpyloric liquid flow, indicate that retrograde duodenogastric
      propelling of contents may be an important determinant for the gastric emptying
      rate.

PMID- 9659667
TI  - Correlation of electrophysiology, neurochemistry and axonal projections of guinea
      pig sphincter of Oddi neurones.
AB  - Sphincter of Oddi (SO) ganglia are comprised of two main types of neurones based
      either on their electrical or neurochemical properties. This study investigated
      whether any correlation exists between the electrical and neurochemical
      properties of these cells. SO neurones were characterized electrically as either
      Tonic or Phasic cells, labelled with neurobiotin, fixed, and processed for beta
      nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-DA) staining and
      choline acetyltransferase immuno-reactivity to identify whether electrically
      characterized neurones were nitrergic or cholinergic. A total of 119 cells were
      analysed in this manner; 45% of cells were Tonic and 37% were Phasic. An
      equivalent number of Tonic (58.1%, 18/31) and Phasic cells (60%, 21/35) were
      choline acetyltransferase (ChAT) positive. Three of 34 Phasic cells were NADPH-DA
      positive, whereas 11/33 Tonic cells were NADPH-DA positive. In none of the
      preparations was ChAT immunoreactivity and NADPH-DA reactivity ever observed in
      the same neurone. Calretinin immunoreactivity was present in a subpopulation of
      both Tonic and Phasic neurones. No correlation was observed between the direction
      of axon projections and the electrophysiological or neurochemical properties of
      the cell. These results suggest that there is a lack of correlation between the
      electrical properties and the neurochemical content of SO neurones. Various
      explanations for these findings are discussed.

PMID- 9659668
TI  - In vitro and in vivo effects of nitric oxide synthase inhibitors and nitric oxide
      inactivators on the South American opossum ileocolonic junction.
AB  - The potential role of nitrergic nerves in the regulation of the South American
      (SA) opossum ileocolonic junction (ICJ) function was investigated. In vitro, the
      effects of nitric oxide (NO) synthase inhibitors and NO inactivators on the non
      adrenergic non-cholinergic (NANC) nerve-mediated relaxations of the circular
      muscle of the SA opossum ICJ were determined by employing isolated strips.
      Electrical field stimulation (0.2-8.0 Hz) caused frequency-dependent NANC
      relaxations. Nicotine and ATP also induced concentration dependent NANC
      relaxations that were abolished by tetrodotoxin (TTX). The relaxation response
      induced by NANC nerve activation was reduced in a dose dependent manner by NO
      synthase inhibitors while vasoactive intestinal peptide (VIP) and sodium
      nitroprusside (SNP) induced relaxations were uninfluenced by these drugs. In
      vivo, the NO synthase inhibitor, L-NAME, administered into the local artery
      caused a raise in intraluminal pressure of the ICJ in anaesthetized SA opossums
      in a L-arginine-preventable manner. Hydroquinone and pyrogallol, while being able
      to reduce, in a superoxide dimutase (SOD) reversible manner, the relaxations
      induced by exogenous NO failed to affect the NANC nerve-induced relaxations.
      Finally, neurones and nerve fibres in the myenteric plexus as well as varicose
      nerve fibres on the circular smooth layer were positive for NADPH-diaphorase
      activity. These findings indicate that nitrergic nerves inhibit ICJ circular
      smooth muscle in vitro and in vivo but cast doubts on the neuromediator being the
      NO radical.

PMID- 9659669
TI  - A comparison of micromanometric and standard manometric techniques for recording
      of oesophageal motility.
AB  - Perfused micromanometric assemblies with an outer diameter of 2 mm or less have
      been developed for use in premature infants and small laboratory animals. Such
      assemblies offer advantages with regard to subject comfort and low perfusion
      rates that make them attractive for use in adults. The aim of this study was to
      investigate the recording fidelity of micromanometric assemblies in the
      measurement of oesophageal peristalsis in adults. Two micromanometric assemblies
      with an outer diameter of 1.8-2.0 mm and a length suitable for use in adults (165
      cm), and containing micromanometric lumina of 0.28-0.35 mm i.d. and a standard
      lumen of 0.6-0.75 mm i.d. were evaluated. Each assembly was tested by measurement
      of pressure rise rate in response to sudden occlusion, and in vivo during
      oesophageal peristalsis by simultaneous comparison with an intraluminal strain
      gauge. At perfusion rates of 0.01-0.15 mL min-1 microlumina achieved pressure
      rise rates of 21-430 mmHg sec-1 that were comparable to 37-390 mmHg sec-1 for the
      standard lumina perfused at 0.15-0.6 mL min-1. During oesophageal peristalsis,
      micromanometric lumina recorded the occurrence and timing of all pressure waves
      accurately when compared with standard lumina and the microtransducer. However,
      microlumina under-recorded pressure wave amplitude to varying degrees dependent
      upon perfusion rate although the performance of microlumina could be improved to
      that of the standard lumen by shortening their length to 70 cm. Micromanometric
      assemblies are suitable for recording oesophageal peristalsis in adults although
      there is some impairment of absolute manometric fidelity. Fidelity can be
      improved by minimizing total assembly length.

PMID- 9659670
TI  - Effect of transdermal application of nicotine on colonic transit in healthy
      nonsmoking volunteers.
AB  - The radio-opaque marker technique (ROMT) is a safe and noninvasive method to
      determine total colonic (TCTT) and segmental colonic transit times (SCTT).
      Previous results have shown that smoking volunteers had significantly longer TCTT
      than nonsmokers, but the underlying mechanism was not clear. We investigated the
      effect of transdermal nicotine application in two different doses in a non-blind
      randomized experiment involving three distinct phases. In phase 1 baseline
      transit times were determined with an abdominal X-ray after a 6-day period of
      marker ingestion and again after the following bowel movement to study the
      influence of a bowel movement just before the X-ray. TCTT was nearly twice as
      high before than after defaecation (42.6 h vs. 25.1 h, P < 0.05). The main
      acceleration was found in the rectosigmoid (RS) (18.6 h vs 7.1 h, P < 0.05) with
      no significant changes in right (RC) and left colon (LC). In phase 2 and 3
      nicotine was applied in two doses of 17.5 mg day-1 and 35 mg day-1 in random
      order. Both doses resulted in a significant decrease of TCTT compared to the
      predefaecation baseline (42.6 h vs 32.2 h/28.2 h, respectively, P < 0.05). Again
      the main effect was located in the RS (18.6 h vs 9.9 h/7.6 h, P < 0.05). Short
      term application nicotine results in a decrease of TCTT which is due to an
      accelerated transit in the RS.

PMID- 9659671
TI  - Lactate production and clearance in exercise. Effects of training. A mini-review.
AB  - Lactate accumulates if pyruvate formation exceeds pyruvate oxidation. Accelerated
      glycogenolysis is essential for lactate production. Glycogen and epinephrine
      enhance glycogen phosphorylase activity and this is higher in type II b than in
      type I fibers. Pyruvate oxidation is enhanced by exercise-induced increase in
      pyruvate dehydrogenase activity and is relatively impaired by low oxygen
      availability and low mitochondrial oxidative capacity. During exercise lactate is
      eliminated in liver, heart, and resting and working muscle. In muscle,
      elimination depends on plasma concentration, fiber type, and fiber conditions.
      Due to influence on hormonal response, mitochondrial oxidative capacity and fiber
      recruitment, training diminishes glycogenolysis and lactate production. Training
      also increases lactate clearance. This reflects increased hepatic capacity for
      gluconeogenesis as well as increased lactate transport capacity and oxidative
      capacity and reduced glycogenolysis in muscle. The fact that endurance
      performance can be predicted from the plasma lactate versus exercise intensity
      relationship illustrates that the plasma lactate level is a finely balanced
      result of the interplay between many factors of importance for endurance
      exercise.

PMID- 9659672
TI  - Short-term intermittent normobaric hypoxia--haematological, physiological and
      mental effects.
AB  - Effects on erythropoiesis and blood pressure as well as physical performance and
      mental effects were studied in 15 healthy subjects during intermittent exposure
      to normobaric hypoxia corresponding to either 2000 m (6 persons) or 2700 m (9
      persons) above sea level; another group (5 persons) also served as controls at
      normoxia. The concept "live high-train low" was used for 10 d consecutively and
      the exposure to hypoxia was 12 h/d. Blood pO2 and oxygen saturation were
      significantly decreased during the 10 d at hypoxia. [Hb] and Hct decreased
      significantly after 2 d in hypoxia and then returned to pre-study levels.
      Erythropoietin was significantly elevated in both hypoxia groups during the
      initial 3-5 d. Reticulocytes were significantly increased during 7 d of hypoxia.
      Submaximal and maximal oxygen uptake, blood pressure at rest and during exercise
      and the profile of mood states (POMS test) did not change during the study. In
      conclusion, intermittent normobaric hypoxia for 10 d resulted in a significant
      stimulation of erythropoiesis. Staying at normobaric hypoxia may serve as a
      complement to an ordinary altitude level sojourn.

PMID- 9659673
TI  - Isokinetic muscle strength and hiking performance in elite sailors.
AB  - The aim of the present study was to describe the isokinetic strength profile and
      its relation to hiking performance in male (SM, n = 15) and female (SF, n = 6)
      elite sailors compared to a group of male control subjects (CM, n = 8) similar in
      age, anthropometry and level of fitness. Eccentric knee extension strength was
      higher in SM compared to CM (P < 0.01). Furthermore, SM were stronger during
      trunk extension (P < 0.05), but not during trunk flexion compared to CM. Overall
      muscle strength was lower in SF compared to SM (P < 0.01) and CM (P < 0.05),
      except for eccentric knee extension strength, where SF and CM did not differ (P >
      0.05). Hiking performance correlated to maximal eccentric and isometric knee
      extensor strength in SF (rs = 0.83-0.88, P < 0.05) and in CM (rs = 0.73-0.77, P <
      0.05) and to maximal eccentric knee extensor strength at high velocity in SM (rs
      = 0.46-0.54, P < 0.05). For a subgroup of hikers in SM (n = 8), hiking
      performance correlated to maximal isometric-eccentric knee extensor strength (rs
      = 0.67-0.74, P < 0.05), whereas no correlations emerged for the non-hikers (n =
      7). Few correlations were observed between hiking performance and maximal
      concentric trunk flexor strength (rs = 0.69-0.92, P < 0.05). Unexpectedly, in SM
      correlations also were observed between hiking performance and maximal strength
      of the trunk extensors (rs = 0.46-0.53, hiker subgroup: rs = 0.64-0.67, P <
      0.05). In conclusion, notably high levels of maximal eccentric knee extensor
      strength were observed for the male and female elite sailors examined in the
      present study. Furthermore, the present results suggest that hiking performance
      depends in part on maximal isometric-eccentric knee extensor strength. The
      maximal strength of the trunk extensors, which potentially stabilizes the lower
      back and spine, also seems to have some importance for the hiking performance of
      top-level sailors.

PMID- 9659674
TI  - Acute badminton injuries.
AB  - During 1990-1994, 1.2% of all sports injuries that required emergency care at the
      University Hospital of Umea were caused by badminton. In 90.7% of the cases the
      patients described themselves as recreational players or beginners. There were
      51.3% minor injuries (AIS 1) and 48.7% moderate injuries (AIS 2). The lower
      extremities were affected in 92.3% of the cases. Achilles tendon ruptures (34.6%)
      and ankle sprains and fractures (29.5%) were the most frequent. By the time of
      the follow-up (10-69 months), 52.6% of the players still had symptoms from the
      injuries and 39.5% had not been able to return to playing badminton. Our data
      indicate the importance of adequate treatment and rehabilitation after acute
      badminton injuries.

PMID- 9659675
TI  - A prospective cohort study of anterior cruciate ligament injuries in elite
      Norwegian team handball.
AB  - The purpose of this study was to examine gender differences in the incidence of
      anterior cruciate ligament (ACL) injuries in a population of high-level team
      handball players. We also wanted to examine injury mechanisms and possible risk
      factors for ACL injuries, including menstrual status. The study was done
      prospectively during the 1993-94, 1994-95, and 1995-96 seasons. We found 28 ACL
      injuries, 23 among women (incidence: 0.31 +/- 0.06 injuries per 1000 player
      hours) and 5 among men (0.06 +/- 0.03 inj./1000 h; P < 0.001 vs women; risk
      ratio: 5.0). Of the 28 injuries, 24 occurred during competition (0.91 +/- 0.19
      inj./1000 h; women: 1.60 +/- 0.35 inj./1000 h; men: 0.23 +/- 0.13 inj./1000 h; P
      < 0.001 vs. women; risk ratio: 7.0) and 4 during training (0.03 +/- 0.02
      inj./1000 h; P < 0.001 vs. competition; risk ratio: 29.9). Nearly all the
      injuries (n = 25) occurred in non-contact situations when the players performed
      high-speed plant-and-cut movements which they were well accustomed to. A reliable
      menstrual history could be obtained in 17 of the 23 cases among females. Five of
      the injuries occurred in the menstrual phase, 2 in the follicular phase, 1 in the
      early luteal phase and 9 in the late luteal phase (chi-square3 d.f. = 13.2; P <
      0.01). The results suggest that there may be an increased risk of ACL injury
      during the week prior to or after the start of the menstrual period.

PMID- 9659676
TI  - Early rehabilitation of acute anterior cruciate ligament injury--a randomized
      clinical trial.
AB  - The efficacy of a 6-week rehabilitation program was evaluated in 100 consecutive
      patients, age 15-42 years, with acute anterior cruciate ligament (ACL) injury.
      Arthroscopy revealed associated lesions in 82% of the patients. Except for
      resections on menisci with large and unstable lesions, no surgery was performed.
      The patients were randomly assigned to supervised training or self-monitored
      training after instruction. RESULTS: At the 6-week follow-up there was no
      difference between the groups with regard to pain at rest, pain during walking,
      or experience of giving-way episodes, Tegner activity level of Lysholm knee
      score. Only 2 of the 100 patients were observed without joint mobility
      restriction. The only significant difference between the groups was the
      improvement of muscle function in men in the supervised training group.
      CONCLUSION: Six weeks' rehabilitation is too short a time period from original
      injury to obtain normal mobility and restored knee function.

PMID- 9659677
TI  - Effects of immobilization and subsequent low- and high-intensity exercise on
      morphology of rat calf muscles.
AB  - After a cast immobilization of 3 weeks, the effects of 4-week remobilization by
      free cage activity or treadmill running on the morphology of the rat soleus and
      gastrocnemius muscles were studied. The studied morphometric parameters were:
      percentage volume of intramuscular connective tissue, capillary density, muscle
      fiber size, number of fibers with a pathological structural alteration, and fiber
      type distribution. In both muscles, immobilization of 3 weeks produced a
      significant increase in the connective tissue volume and number of fibers with
      pathological alterations, with a similar decrease in the capillary number and
      fiber size. At the same time, the relative amount of type I fibers decreased and
      type IIA fibers increased. Free remobilization and especially intensified
      remobilization by treadmill running significantly restored these values towards
      controls. These findings indicate that in rat soleus and gastrocnemius muscles
      immobilization-induced accumulation of intramuscular connective tissue, capillary
      loss, reduction in fiber size, accumulation of fibers with pathological
      structural alterations, and changes in fiber type distribution are to a great
      extent reversible phenomena, especially if remobilization is intensified by
      physical training. In clinical practice, this suggests that in patients with
      musculoskeletal injuries the postimmobilization rehabilitation should be early
      and effective.

PMID- 9659678
TI  - The reliability and validity of an instrumented staple system for in vivo
      measurement of local bone deformation. An in vitro study.
AB  - We recently presented a pilot study using an instrumented staple system for
      measuring in vivo local deformation on tibia. Methodological development has now
      proceeded in vitro. Consecutively, we performed 1. a sheep bone micrometer study,
      2. a sheep bone four-point bending test and 3. a pig bone four-point and three
      point bending test. This was done in order to secure a standardized application
      of the staple, to analyze the interaction of the bone and the staple and to
      secure calibration and the reliability of the system to be used in vivo. With
      reference to the above studies: 1. There was a linear relationship (r = 0.998)
      between the applied deformation of the bone and the measured deformation of the
      staple. ICC values ranged from 0.866 to 0.997. 2. An excellent intra-test
      reliability as well as linearity between staple measures and surface strain on
      the bone was observed (r = 0.998). 3. The slope of regression lines (k) was min
      7.2 and max 9.4. The results from this test are used for calibration of the
      instrumented staple. Great variations were found between tension and compression
      measurements. However, within each test the SD was negligible. We suggest that
      the instrumented staple system may be calibrated in vitro and validly used for in
      vivo measurement of local bone deformation.

PMID- 9659679
TI  - Hyperextension trauma to the elbow joint induced through the distal ulna or the
      distal radius: pathoanatomy and kinematics. An experimental study of the ligament
      injuries.
AB  - Loads applied to the forearm result in hyperextension of the elbow. The
      pathomechanics of hyperextension trauma with load applied to the distal radius
      and ulna were studied in 10 macroscopically normal cadaver elbow joint specimens
      to reveal patterns of injury with radial traction (n = 5) compared to ulnar
      traction (n = 5). The mean age of the donors was 60.8 years (range 33-74).
      Kinematic testing was performed in an experimental 3D-kinematic loading
      apparatus. The extension range of motion increased by 20.9 degrees +/- 2.9
      degrees after joint loading. Hyperextension loads induced joint laxity during
      flexion of less than 60 degrees. In both groups, the changes were significant in
      joint flexion during forced valgus and external rotation, but were not
      significant in flexion during forced varus and internal rotation. In both groups,
      the same four lesions were produced: 1) Anterior capsule rupture, 2) L-formed
      rupture of the origin of the pronator muscle with elongation of the anterior
      bundle of the medial collateral ligament, 3) partial rupture of the lateral
      collateral ligament and 4) small cartilage damage to the posterior or
      anteromedial edge of the ulna. In conclusion, hyperextension trauma to the elbow
      joint induced through the distal ulna or the distal radius produced the same
      pattern of injury as reported in hyperextension of the elbow with traction to the
      forearm when free rotation of the radius relative to the ulna was allowed.

PMID- 9659680
TI  - Stress, control, and coping in elite athletes.
AB  - The main object of this study was to explore different dimensions of the stress
      experience and the following coping efforts among elite athletes. Sixty-nine
      Norwegian Winter Olympic athletes, competing in the Lille-hammer Games in 1994
      participated in the study. Recall of the most stressful experiences was reported
      through open-ended questions following the Olympic Games, and the actual time of
      the experience with the following coping efforts were measured with the COPE
      inventory (19). The stress was mainly experienced during the time period prior to
      the competition. External distractions and expectations were the most frequently
      reported stress experiences. The coach was viewed as a major source of stress by
      some athletes, with a subsequent lack of control and low satisfaction with
      performance. Type of stress more than the time of the experience seemed to have a
      detrimental effect on performance. Problem-focused coping strategies were
      employed at all times, while cognitive defense strategies were employed more days
      before (time phase 1) and after the competition (time phase 4).

PMID- 9659681
TI  - [The basic traits of respiratory management].

PMID- 9659682
TI  - [The sodium-potassium-chloride cotransport of the cell membrane].
AB  - Discovery and active exploration of the furosemid-sensitive derived-active co
      transport of sodium-potassium-chlorine ions took place in the end of 1970-es-1980
      es. This transportation mechanism was discovered in various types of cells, both
      of plant and of animal origin. This review describes properties of the
      transportation process, which was most comprehensive explored in experiments with
      erythrocytes, epithelium cells and muscles. The review covers the following
      properties: anion and cation selectivity of the chlorine transportation, its
      sensitivity to the specific blocking agents (furocemid, bumetanid, etc.),
      stoichiometry of the transportation process, etc. For energy source, the chlorine
      transportation is based on transmembrane electrochemical gradient for sodium
      ions. The article provides the most recent results of investigation of the
      chemical nature of the molecule of the chlorine membrane transport. Based on
      various studies, the molecule of this protein weighs from 120 to 200 kD, includes
      about 1200 amino acid residua, and forms long cytoplasmatic NH2 and COOH-termini.
      The gene encoding the amino acid sequence has been cloned. The article discusses
      the issues of regulation of the chlorine transportation. Humoral control of
      intensity of the chlorine transportation has been mostly studied in experiments
      with plain muscles, the issues related to nervous regulation--with only skeleton
      muscle fibers. The article provides specific data on the mechanisms of the above
      types of the physiological regulation of active chlorine transportation. In
      general, the humoral factors, which increase the intracellular concentration of
      cAMF stimulate chlorine transportation. On the contrary, the hormones, which
      increase concentration of cGMF in cytoplasm reduce its activity in plain muscles.
      The discussion of the mechanisms of the nervous controls of the chlorine
      transportation in the skeleton muscles includes the original results of the
      author. These results indicate that the suppressive influence of the motor
      innervation on intensity of the chlorine transportation involves the non-quantum
      acetilcholine and glutamate secreted from the motor nerves. These agents produce
      Ca(2+)-dependent molecules of nitrogen oxide in sarcoplasm, which act in the
      retrograde mode on the nervous terminal and activate there the synthesis of cGMF.
      Disruption of this bilateral transsynaptic signalization resulting from cutting a
      nerve of blocking of its axoflow creates more active chlorine transportation and
      subsequent de-innervation changes in properties of the muscle fibers. The
      functions of chlorine transportation, which are best studies as of today and
      therefore, discussed in more detail in the review, include participation of this
      process in the regulatory rehabilitation of the volume of various cells in non
      isotonic medium, and the role of chlorine transportation in development of a
      negative charge at the interior side of membrane of the skeleton muscle fibers.
      The former function essentially means that dehydration of a cell in the
      hypertonic medium increases activity of the sodium, potassium and chlorine co
      transport directed to the cell, resulting in increase of the amount of the
      osmosis-active cytoplasm material, and inflow of water, which fully restores the
      cell volume in these conditions. Starting from the pioneer studies by Hodgkin and
      Horowicz [correction of Hojkin and Gorovits], the role of chlorine ions in
      forming a charge on the membrane of excited cells has been generally interpreted
      as exclusively passive. I.e., distribution of these ions over both sides of
      membrane was assumed as equilibrium with the existing values of the membrane
      potential in the non-excited state. The review provides data obtained in the
      recent decade, which have proved that the non-excited membrane potential in
      muscle fibers is co-created by the diffusional potassium and chlorine potential.
      (ABSTRACT TRUNCATED)

PMID- 9659683
TI  - [The effect of neurotensin on the cardiovascular system].
AB  - Neurotensin is a peptide involved in regulation of cardiovascular system.
      Neurotensin immunoreactivity is found in myocardium, conduction system of the
      heart, intracardiac ganglion cells, coronary vessels. High content of this
      peptide is also determined in structures of sympathoadrenal system. This creates
      the possibility of hormonal neurotensin action on the heart following sympathetic
      activation. Neurotensin accelerates heart rate, increases myocardial
      contractility, affects central haemodynamics, regional blood flow and coronary
      circulation. Neurotensin modulates autonomic influences on the heart and plays
      role in mechanisms of cardiac arrhythmogenesis, especially in dynamics of vagally
      induced cardiac rhythm disorders. Cardiovascular effects of this peptide may be
      associated with direct influence on the heart and vessels, stimulating action on
      release of histamine and catecholamines and activation of capsaicin-sensitive
      afferent neurons which contain calcitonin-gene related peptide and substance P.
      Cardiovascular action of neurotensin is species dependent and it is followed by
      pronounced tachyphylaxis. Cellular mechanism of neurotensin action is associated
      with stimulation of phosphoinositide turnover, elevation of intracellular calcium
      and cyclic nucleotides level.

PMID- 9659684
TI  - [GABA--the basic mediator of excitation in the early stages of hippocampal
      development].
AB  - GABA is the principal neurotransmitter of inhibition in the adult mammalian
      brain. However, at early stages of development, including embryonic period and
      first week of postnatal life, GABA plays the role of main neurotransmitter of
      excitation. The paradoxical excitatory effect of GABA is due to an inversed
      chloride gradient and therefore a depolarizing direction of GABA-A receptor
      mediated responses. In addition, another type of GABAergic inhibition mediated by
      postsynaptic GABA-B receptors is not functional at early stage of life. In the
      neonatal rat hippocampus, GABA, acting via GABA-A receptors, activates voltage
      gated sodium and calcium channels and potentiates the activity of NMDA receptors
      by reducing their voltage dependent Mg2+ block. The temporal window when GABA
      exerts excitatory actions coincides with a particular pattern of activity of
      hippocampal neuronal network that is characterized by periodical giant
      depolarizing potentials (GDPs) reminiscent of interictal-like epileptiform
      discharges. Recent studies have shown that GDPs result from the synchronous
      discharge of GABAergic interneurons and principal glutamatergic pyramidal cells
      and are mediated by the synergistic excitatory actions of GABA-A and glutamate
      receptors. GDPs provide synchronous intracellular Ca2+ oscillations and may
      therefore be implicated in hebbian modulation of developing synapses and activity
      dependent formation of the hippocampal network.

PMID- 9659685
TI  - [The lateral septal nucleus: its morphological and functional organization and
      its role in the formation of chronorhythms].
AB  - The lateral septal nucleus (LSN) is the largest septal nucleus and occupies one
      of the most strategically important positions in the forebrain, connecting the
      structures of the limbic system with different sites of the brain stem. Such a
      situation obliges LSN not only to participate in the regulation, but also to
      implement overall coordination and modulation of various visceral and somatic
      functions. The review deals with the general characteristic of the septal
      complex, the functional morphology, pre- and postnatal ontogenesis, afferent and
      efferent connections, mediator and modulator nature of LSN fibers. Special
      attention is paid to the participation of LSN in the neuroendocrine regulation of
      the sexual system. On the basis of literature and our own experimental findings
      it is shown that the LSN is a chronoregulatory structure which is responsible for
      the biorhythmologic organization of the functions of the mammalian organism.

PMID- 9659686
TI  - [The dynamics of the secretion of linoleic acid as a component of the lipid
      classes with milk and their metabolism in the body of cows].
AB  - The paper is devoted to the questions of metabolism of the lipid classes and
      essential fatty acids in the ruminant organism and secretion of those acids with
      milk. The lipid classes, such as triacylglyceroles, phospholipides and
      cholesterol ethers, containing linoleic acid and others acids of that family,
      their function, structure, quantity and transport in the organism are
      characterized. The physiological lactation standards (duration, breed, season and
      diurnal variations) are described more exactly. The author's own and literature
      data concerning secretion of lipid classes, containing linoleic acid, on
      lactation periods (in the period of colostrum secretion and in all periods of
      milk secretion), lipid transport, transformation and metabolism in the digestive
      tract and the liver are discussed. The correlation of lipid classes and
      corresponding fatty acid composition in the forage, milk, colostrum and plasma of
      arterial and venous blood, obtained from ruminants, is characterized.

PMID- 9659687
TI  - African swine fever virus infection of the bushpig (Potamochoerus porcus) and its
      significance in the epidemiology of the disease.
AB  - Warthog (Phacochoerus aethiopicus), giant forest hog (Hylochoerus meinertzhageni)
      and bushpig (Potamochoerus porcus) are known to be susceptible to infection with
      African swine fever (ASF) virus. Little however, is known about the ecology of
      the disease in the bushpig. This study has shown that the bushpig remains
      viraemic for between 35 and 91 days following infection during which time it is
      able to infect the tick vector O. moubata. These ticks were able to transmit the
      disease to pigs. The virus persists in the lymphatic tissues for less than 34
      weeks. Bushpigs infected with LIL 20/l virus but not VIC T90/l virus transmitted
      infection to in-contact pigs. Infected domestic pigs did not transmit the
      infection to in-contact bushpigs. ASF virus was able to replicate in in vitro
      cultures of bushpig leucocytes and endothelial cells. Recovered bushpigs could be
      reinfected with some strains of virus but not others. While it has been
      demonstrated that bushpigs remain carriers of ASFV following infection a complete
      understanding of their significance in the epidemiology of the disease awaits
      further investigations of their association with O. moubata.

PMID- 9659689
TI  - The gene for component-II of botulinum C2 toxin.
AB  - The gene encoding component-II of the Clostridium botulinum C2 toxin was cloned
      from the chromosomal DNA of C. botulinum type C strain (C)-203U28, and the
      nucleotide sequence was determined. The gene (bc2h) encodes a protein with 721
      amino acid residues and is located at 247 bp downstream of the gene for component
      I. The N-terminal 16 amino acids were identical to those obtained by analysis of
      the purified component-II toxin. The ORF for bc2h had only 39% homology at the
      amino acid level with the C.perfringens iota-Ib protein and an ATP/GTP binding
      site which is present in the iota-Ib protein is missing from the protein encoded
      by bc2h. Both genes had a homologous region that predicts a transmembrane
      segment.

PMID- 9659688
TI  - Rapid and sensitive detection of Staphylococcus species in milk by ELISA based on
      monodisperse magnetic particles.
AB  - Staphylococcus spp. are the single most important cause of mastitis in dairy
      cows. Aiming for a rapid and sensitive method for detection of staphylococci, a
      magnetic bead-based enzyme-linked immunosorbent assay (ELISA) employing MAb for
      the detection of staphylococci in milk was developed. Pretreatment of the sample
      with lysostaphin increased the sensitivity of the assay. The method is specific
      for most of staphylococci which cause mastitis in bovines, detects between 10(4)
      10(5) organisms per ml and takes three hours. Thus, the principle for
      staphylococci ELISA based on monodisperse magnetic beads is a way for rapid
      detection of staphylococci in milk and possibly also for detecting staphylococci
      by direct testing of other clinical specimens. The system may be automated.

PMID- 9659690
TI  - Characterization of four Flavobacterium columnare (Flexibacter columnaris)
      strains isolated from tropical fish.
AB  - Four Flavobacterium columnare strains (AJS 1-4) were isolated from black mollies
      (Poecilia sphenops) and platies (Xiphophorus maculatus), showing white spots on
      the back, head and skin ulcers. The isolates developed characteristic rhizoid
      yellow pigmented colonies on Shieh agar and typical growth in Shieh broth. They
      were Gram-negative, filamentous bacteria exhibiting flexing movements. When
      compared to F. columnare strains isolated from temperate fish, it was noted that
      the four strains originating from tropical aquarium fish are more capable of
      growing at higher temperatures, the opposite being true for the strains isolated
      from temperate fish. Biochemical characterization and agglutination tests proved
      that the isolated strains could be classified as F. columnare. Low minimal
      inhibitory concentration (MIC) values were found for chloramphenicol,
      erythromycin, furazolidone, kanamycin, lincomycin, nalidixic acid,
      oxytetracycline and streptomycin. MIC values were high for colistin,
      sulfamethoxazole and neomycin. Pathogenicity studies were performed on black
      mollies. When these animals were submersed in an infective solution of the F.
      columnare strains, a marked difference in virulence was noted among the four
      isolated strains, strain AJS 1 being the most virulent one and strain AJS 4 being
      of low virulence.

PMID- 9659691
TI  - Transmission of canine gastric Helicobacter salomonis infection from dam to
      offspring and between puppies.
AB  - H. bizzozeronii CCUG 35045, a new canine gastric Helicobacter spp. was used for
      experimental infection of four weaned puppies at 7 weeks of age. Controls were
      four nonchallenged puppies. The puppies originated from two dams which had
      Helicobacter salomonis infection in biopsy samples taken 3 weeks before the
      delivery but which had urease, brush cytology and culture-negative biopsy samples
      taken 7 weeks after antimicrobial treatment (metronidazole, amoxicillin, bismuth
      subcitrate). Both dams were detected urease- and Helicobacter-positive again
      three and a half months after therapy. Dam B was shown to be colonised with the
      similar genotype of H. salomonis for more than 2 years. Unexpectedly, H.
      salomonis was also cultured from gastric biopsy samples of the nonchallenged
      puppies three times during 7 months. When H. salomonis isolates of dams and
      puppies were studied by ribotyping (HaeIII, ClaI or PstI) they were shown to be
      identical although the HaeIII and PstI REA patterns of dam A differed from the
      patterns of dam B and nonchallenged group by one fragment. PFGE pattern analysis
      of NotI digests, however, revealed that the isolates of the puppies were
      identical with the isolates of dam B, and differed from the isolates of dam A.
      The isolates of the dams and puppies in the nonchallenged group were
      metronidazole-resistant. The antimicrobial therapy had merely suppressed, but not
      eradicated, the infection from dams. These studies suggested that puppies may
      acquire gastric Helicobacter infection from dams during the lactation period and
      puppies can infect each other during their early life. PFGE pattern analysis was
      shown to be a more distinguishing method than ribotyping to study the similarity
      of the isolates.

PMID- 9659692
TI  - Detection of Lawsonia intracellularis, Serpulina hyodysenteriae, weakly beta
      haemolytic intestinal spirochaetes, Salmonella enterica, and haemolytic
      Escherichia coli from swine herds with and without diarrhoea among growing pigs.
AB  - A polymerase chain reaction (PCR) was optimized to detect Lawsonia
      intracellularis in faeces from naturally infected pigs. By combining a boiling
      procedure to extract DNA and a nested PCR procedure, a detection limit at 2 x
      10(2) bacterial cells per gram of faeces was achieved. The optimized PCR was used
      together with conventional culture techniques to detect Serpulina hyodysenteriae,
      weakly beta-haemolytic intestinal spirochaetes (WBHIS), Salmonella enterica, and
      haemolytic Escherichia coli, in a case control study to examine selected risk
      factors for the development of diarrhoea in growing pigs. Herds with diarrhoea
      were selected as cases and randomly chosen herds without diarrhoea were chosen as
      controls. Infection with L. intracellularis significantly enhanced the chance of
      diarrhoea. S. hyodysenteriae, WBHIS group IV (Serpulina pilosicoli), and S.
      enterica were isolated only from case herds which indicate that these species may
      influence the development of diarrhoea. In addition, herd-type had a significant
      impact, that is specific pathogen-free herds showed an odds ratio at 0.2 relative
      to conventional herds for the development of diarrhoea.

PMID- 9659693
TI  - Significant increase in antibiotic resistance of Salmonella isolates from human
      beings and chicken meat in Thailand.
AB  - A total of 1715 Salmonella strains, including 600 S. enteritidis, 290 S.derby,
      257 S. Weltevreden, 122 S. 1,4,5,12:i:-, 235 S. anatum, and 211 S. typhimurium,
      originating from 1308 human beings and 407 frozen chicken meat specimens
      collected in 1993 and 1994 were tested for antibiotic resistance. The disk
      diffusion method was used with nine disks of chloramphenicol, ceftriaxone,
      amikacin, kanamycin, ampicillin, sulfamethoxazole plus trimethoprim, nalidixic
      acid, gentamicin and ofloxacin. The resistance rates of human beings isolates in
      1994 to ceftriaxone, amikacin and kanamycin were, respectively, 10.7%, 8.6%,
      17.8% in S. enteritidis; 23.1%, 17.3% 33.0% in S. derby; 30.9%, 40.2%, 60.4% in
      S. weltevreden; 16.1%, 17.7%, 70.9% in S.1, 4, 5, 12:i:-; 25.7%, 21.6%, 24.7% in
      S. anatum; 18.9%, 15.7%, 37.8% in S. typhimurium, while those isolates in 1993 to
      the same three antibiotics were, respectively, 1.8%, 0.6%, 3.7% in S.
      enteritidis; 0.8%, 0%, 9.1% in S.derby; 1.8%, 2.7%, 10.8% in S. weltevreden;
      3.8%, 0%, 23.0% in S.1, 4, 5, 12:i:-; 2.2%, 2.2%, 6.7% in S. anatum; 4.5%, 1.5%,
      10.6% in S. typhimurium. It was shown that the resistance rates in 1994 were
      significantly higher than those in 1993. All isolates were susceptible to
      ofloxacin with the exception of one isolate.

PMID- 9659694
TI  - [Measuring bone density with ultrasound--ready for general practice?].
AB  - Osteoporosis is characterized by low bone mass, loss of bone structure and/or
      typical fractures (vertebrae, radius, hip). The costs for the treatment of hip
      fractures in Germany are about 1 billion DM per year, the mortality rate after
      hip fractures is between 10 and 30% within the first year. Low bone mass is an
      important risk factor for the development of fractures; so far however, no
      procedure for the measurement of bone density has been able to 100 percent
      differentiate between patients with established osteoporosis and healthy people
      of the same age. This is due to the fact that the defect in bone structure
      causing the disease could not be measured so far. Quantitative ultrasonometry
      (QUS) is a new, non-invasive, radiation-free method for the in vivo measurement
      of bone density and bone structure. Measurements at the calcaneus and at the
      phalanxes have shown the equivalence of QUS compared to radiological methods in
      prospective studies with regard to the prediction of hip fractures. Furthermore
      it was shown that the beneficial osseous effects of postmenopausal
      estrogen/gestagen replacement therapy can be detected by QUS. Since QUS is
      considerably cheaper and the devices are easily transportable, this method is a
      valuable supplement in the range of diagnostic tools in osteology. Its clinical
      value however depends on the experience of the user and it should be applied in
      patients only together with medical history, physical examination and perhaps
      additional imaging procedures. It was not the inadequate methodology that has
      brought osteodensitometric methods into discredit but the undifferentiated
      handling by inexperienced users.

PMID- 9659695
TI  - [Indications and technique of the M-U abdominal incision and initial clinical
      results of modified abdominoplasty].
AB  - The M-U-abdominoplasty introduced here has been developed to generate an even
      tightening of the central and the lateral parts of the abdominal wall. In
      contrary to the standard method, a more pronounced accentuation of the waist and
      an aesthetically more advantageous course of the scars can be achieved.
      Application of the M-U-abdominoplasty is especially recommended in cases of
      previous liposuction or undermining of the abdominal wall, resulting in a
      stronger relaxation of the lateral than the central parts. A stressed tightening
      of the lateral abdominal wall can be achieved by a soft coursed, M-shaped,
      cranial incision line, which is united with a broad U-shaped caudal incision
      line. The length of the U-incision determines the length of the M-shaped
      incision. Only a limited undermining of the abdominal wall above the umbilicus is
      needed, which minimises the risk of wound-healing impairment caused by nutrition
      defects.

PMID- 9659696
TI  - [Measuring bone density with ultrasound osteodensitometry--results of a pilot
      study].
AB  - Osteoporosis is a systemic bone disease with a decrease in bone structure and
      increased risk of fractures. The primary diagnosis of osteoporosis and the
      surveillance of therapeutic interventions is based either on laboratory or on
      radiological diagnosis. In a pilot study encompassing 274 women the routine use
      of ultrasound osteodensitometry (QUS, Lunar Achilles) of the os calcaneus was
      validated and tested. Velocity of the ultrasound signal (SOS) and frequency
      attenuation (BUA) were measured and the proprietary index stiffness calculated.
      In 47 women ultrasound data were compared with the DXA measurements. Results from
      both methods correlated significantly. Postmenopausal patients with HRT had
      significant better QUS values than those without HRT. Results from both
      diagnostic methods (QUS versus DXA) correlated significantly. Women with HRT
      showed significantly increased bone measurements compared to those without HRT.
      This correlated with an increase in bone metabolism. QUS of the os calcaneus was
      easy to perform, without time spent or inconvenience for and with high acceptance
      by the volunteers/patients. The conformity of the results of the different
      methods (DXA, QUS) may--if the follow up study confirms these results--lead to a
      routine use of QUS for screening and therapy monitoring.

PMID- 9659697
TI  - [Intracytoplasmic sperm injection (ICSI) after previous failure of heterologous
      insemination].
AB  - We report on our experiences with 25 married couples that approached us for
      intracytoplasmatic sperm injection (ICSI) after previous failure of artificial
      insemination by donor (AID). AID has been carried out in several specialized
      fertility centers. We traditionally refrain from donor semen procedures. All
      patients have undergone at least 4 treatment cycles of AID, the maximum was 20.
      With exception of one all patients have been inseminated after ovarian
      hyperstimulation according to different protocols (e.g. GnRH-A/FSH, hMG; CC/hMG).
      Prior to ICSI we have confirmed male subfertility being in all patients of severe
      grade. All patients have been proven to have ejaculated spermatozoa. We have
      performed 71 treatment cycles for ICSI so far, 19 patients have become pregnant,
      3 have aborted. The pregnancy rate per cycle is 26%, per embryo transfer 30%, and
      per patient 76%. We think that these results are primarily caused by so far
      unknown defects in oocytes and their function during fertilization. Besides, we
      assume psychosomatic causes maybe involved.

PMID- 9659698
TI  - [Soluble adhesion molecules in patients with pre-eclampsia].
AB  - Plasma concentrations of the circulating adhesion molecules ICAM-1 (CD54), VCAM-1
      (CD106) were determined in 31 women with pre-eclampsia, 9 women with HELLP
      syndrome, and 13 women with transient pregnancy induced hypertension (PIH). Data
      were compared with a control group of 157 healthy pregnant women of the same
      gestational age. Furthermore, concentrations of circulating E-selectin (CD62E), P
      selectin (CD62P), and PECAM-1 (CD31) were determined in a subpopulation of 17
      women with pre-eclampsia. Plasma concentrations of circulating ICAM-1, VCAM-1, E
      selectin, and PECAM-1 were significantly elevated in women with pre-eclampsia
      compared to healthy control pregnant women. Circulating ICAM-1 and VCAM-1 levels
      were also significantly elevated in the pre-eclampsia group compared to women
      with PIH. Concentrations of circulating P-selectin varied strongly in all
      experimental groups (SD > 70% of the mean), most likely reflecting various
      degrees of thrombocyte degranulation in the individual samples. Finally,
      longitudinal profiles of cICAM-1 and cVCAM-1 concentrations were determined in
      123 healthy pregnant women between the 16th and the 42nd week of gestation. This
      analysis identified cICAM-1 and cVCAM-1 as tightly regulated plasma parameters
      that varied in a small concentration range. Concentrations of cICAM-1 and cVCAM-1
      did not vary during pregnancy and the determined concentrations corresponded to
      the reported reference levels of nonpregnant individuals.

PMID- 9659699
TI  - [Primary endocrine therapy as pre- and perimenopausal metastatic breast carcinoma
      with leuprorelin acetate depot. German Leuprorelin Study Group].
AB  - In an open, prospective, multicentre phase III clinical trial 73 patients with
      newly diagnosed, metastatic breast cancer were enrolled. Most of them were
      hormone-receptor-positive. All patients were pre- or perimenopausal and treated
      with monthly sc. injections of 3.75 mg leuprorelinacetate-depot as monotherapy
      until disease progression. 50/73 patients (68.5%) had low-risk metastatic
      disease. A marked reduction of gonadotropin levels resulted in a profound and
      sustained suppression of the oestradiol levels to castration range (30 pg/ml)
      during the entire treatment period. The overall response rate based on the best
      response during treatment was as follows: CR + PR in 25/73 (34.2%) [25.1-44.4%]
      and CR + PR + SD in 42/73 patients (58%) [47.2-67.4%] respectively. The median
      time to progression (TTP) was 6 months and the median overall survival (OS) 24.3
      months. Both parameters differed significantly when responder (CR/PR) and non
      responder (NC/PD) were compared: 18.6 +/- 2.4 [13.9-23.4] vs. 5.8 +/- 0.6 [4.7
      7.0] months (TTP, p < 0.0001) and 41.5 +/- 3.0 [35.5-47.5] vs. 15.6 +/- 2.4 [11.3
      20.5] months (OS, p = 0.0019). The median duration of response was 12 (range: 3
      48) months. Premenopausal low-risk patients without previous adjuvant treatment
      after primary surgery showed the best response during the GnRHa treatment. The
      main side effects (hot flushes, increased sweating, headache etc.) were related
      to oestradiol suppression. Treatment was well tolerated leading in only one case
      to a premature withdrawal due to side effects. Leuprorelinacetate-depot is a safe
      and effective palliative drug for pre- and perimenopausal metastatic breast
      cancer patients. Like other GnRH-agonists which have been evaluated for this
      indication, leuprorelinacetate-depot can be used as first-line endocrine
      treatment in these patients.

PMID- 9659700
TI  - [Gameprost, sulproston and dinoproston for induced abortion in the 15th-24th week
      of pregnancy].
AB  - In a randomized, prospective study at the Dept. of Obstetrics and Gynecology of
      the University Hospital of Giessen 4 different ways of inducing abortions with
      prostaglandins were tested between the 15th and 24th week of gestation. The aim
      of the study was to determine the best approach to inducing abortion in order to
      minimize the psychological and physical stress to the patient. Subjects
      randomized to the first two groups got a single cervical installation of either
      0.5 mg Dinoprostongel (Prepidil, N = 22) or 0.5 mg Sulprostongel (Nalador, N =
      21). Six hours later, i.v. infusion with Sulproston (8.3 micrograms/min) was
      started and continued until the abortion was complete. Patients randomized to the
      third and fourth group received either 0.5 mg Dinoprostongel intracervically (N =
      15) or 1 mg Gemeprost vaginal suppositories (Cergem, N = 21) every 6 hours until
      the cervix was 1-2 cm dilated. Subsequently the patients received an i.v.
      infusion with Sulproston until the abortion was complete. In the first group with
      intracervical application of Sulproston the total time until abortion was 17.8 h
      +/- 7.8 h. This was shorter than following a single application of Dinoprostongel
      (22.5 h +/- 14.7 h). Although there was a five hours difference, the between
      group differences were not statistically different because of a wide range in
      values following Dinoproston treatment. This range could not be explained by the
      age of the mother, week of gestation or parity. In the group receiving multiple
      intracervical applications of Dinoproston the time till expulsion was twice as
      long as that after multiple vaginal suppositories of Gemeprost (33.8 h +/- 13.9 h
      vs. 15.6 +/- 6.0 h, p < 0.01). The time span until a cervical dilatation of 1-2
      cm was 27.0 h +/- 13.7 h in the group with repeated Dinoproston application. This
      period of time was more than twice the time span seen in the group with repeated
      Gemeprost application (12.5 h +/- 4.2 h, p < 0.01). On the average four
      treatments with intracervical Dinoprostongel were required while the average with
      Gemeprost vaginal suppositories was two to achieve a cervical dilatation of 1-2
      cm. Furthermore in 7 of 21 cases treatment with Gemeprost achieved the expulsion
      of the fetus without Sulproston infusion (11.4 h +/- 5.2 h). Comparing single
      versus repetitive prostaglandin application we could demonstrate that the
      duration of Sulproston infusion was cut in half after repeated therapy with
      Gemeprost. We conclude that repetitive application of Gemeprost vaginal
      suppositories decreases the time to abortion and subject discomfort tremendously.
      The application of Gemeprost suppositories provides the easiest and most
      efficient therapeutic approach for both patients and staff. Furthermore the
      regiment that provided the best results was also the most cost-effective (range
      180,-DM to 317,- DM per case).

PMID- 9659701
TI  - [Dyspareunia and algopareunia].
AB  - On the basis of sexuological examination of 152 married women with pelvic
      inflammatory disease it is proposed to use the term of dyspareunia in patients
      who have pains during coitus and who are dissatisfied with the course of sexual
      intercourse. For probands who had unpleasant or even painful feelings during
      coitus but were in 93% of cases satisfied with sexual life, it would be suitable
      to use the term of algopareunia.

PMID- 9659702
TI  - [Interstitial pregnancy and management with a single systemic administration of
      methotrexate].
AB  - We report on a patient with an interstitial pregnancy treated with a single
      systemic dose of Methotrexate (50 mg/m2). After Methotrexate, human chorionic
      gonadotropin levels decreased to < 5 mIU/ml within 25 days. Six months later, a
      contrast sonography showed patency of both tubes.

PMID- 9659703
TI  - [Gynecologic endocrinologic information sources in the internet].
AB  - Within the last months a great number of internet pages have become a highly
      interesting source of up-to-date information in gynecological endocrinology. Most
      of these World Wide Web-pages present actual scientific fields and abstracts with
      close relations to basic science, while clinical discussion groups are still
      rare. The potential of internet presentations will strongly influence
      communication in cases of gynecological endocrinology.

PMID- 9659704
TI  - Analytical applications of synchrotron radiation.

PMID- 9659705
TI  - Determination of the total arsenic concentration in human urine by inductively
      coupled plasma mass spectrometry: a comparison of the accuracy of three
      analytical methods.
AB  - Measurement of arsenic (As) in biological samples such as urine has important
      clinical applications and is being undertaken more frequently in epidemiologic
      studies because of concern about the carcinogenicity of low to moderate levels of
      As exposure. The objective of this study was to evaluate and improve the accuracy
      of As determination in urine by inductively coupled plasma mass spectrometry (ICP
      MS). Determination of As in biological samples by ICP-MS is difficult for two
      reasons: the formation of the molecular ion 40Ar35Cl, which overlaps with
      monoisotopic As at a mass-to-charge ratio (m/z) of 75 (causing spectral
      interference), and signal enhancement due to organic matrix (nonspectral
      interference). Available procedures were examined, including the application of
      different correction procedures using 40Ar37Cl and 16O35Cl molecular-ion
      formation; the addition of N2 into plasma or nebulizer gas flows; and the
      addition of organic molecules to the sample and to calibration standards to
      eliminate or correct for interference due to molecular-ion formation. The
      accuracy and precision of determination of As [m/z 75, ionization potential (IP)
      9.81 eV] with use of an internal standard was also investigated. Three elements
      were studied as candidate internal standards: germanium (Ge: m/z 74, IP 7.90 eV),
      indium (In: m/z 115, IP 5.79 eV), and tellurium (Te: m/z 128, IP 9.01 eV). It was
      found that these three elements performed more or less equally well with Ar-N2
      plasma; it was also found that accuracy was significantly improved when Te was
      used as the internal standard instead of Ge or In for ethanol-added samples. Our
      results indicate that accurate and precise measurement of As in urine by ICP-MS
      can be obtained by either of two methods (< 5% error, approximately 2% RSD, limit
      of detection 0.1 ng ml-1): (1) the addition of 1% N2 to plasma gas flow or 3% N2
      to nebulizer gas flow, along with use of any of the internal standards tested, or
      (2) the addition of ethanol to the sample and to calibration standards, with use
      of Te as the internal standard. The most accurate results (< 1% error) for
      National Institute of Standard and Technology Standard Reference Material (NIST
      SRM) 2670 (toxic elements in urine) were obtained with Ar-N2 plasma with either
      Te or In as the internal standard.

PMID- 9659706
TI  - Molybdenum intake of adults in Germany and Mexico.
AB  - Molybdenum is an essential micronutrient. It plays a complex role in the
      ecosystem, because the metal is a part of a cofactor for several important
      enzymes in human, animal and plant metabolism. The physiological requirement for
      this element is relatively low. Our investigations were aimed at determining the
      Mo intake of adults in Germany and Mexico by means of duplicate portion
      technique. Molybdenum was estimated in the food duplicate samples by inductively
      coupled plasma atomic emission spectrometry. In 1988, 1992 and 1996 the Mo
      consumption of humans was investigated in 14 test groups of persons with mixed
      diets. Each test population consisted of seven men and seven women. Furthermore,
      in 1996 the Mo intake of 10 female and 10 male vegetarians and of two Mexican
      test groups was also determined. Different factors, such as sex, time of
      investigation, location and eating habits have an effect on the individual Mo
      intake, Molybdenum intake of adults with mixed diets has increased significantly
      from 1988 to 1996. Furthermore, results of our study showed that Mo intake of
      German adults differs depending on location and the kind of diet. German women
      with a mixed diet consumed 89 micrograms d-1 in 1996 and men 100 micrograms d-1.
      In comparison, female and male vegetarians consumed 179 micrograms d-1 and 170
      micrograms d-1, respectively. There was a significant difference in Mo
      consumption between German and Mexican test persons. Mexican women consumed on
      average 162 micrograms d-1 and Mexican men 208 micrograms d-1. The Mo requirement
      of adults amounts to about 25 micrograms d-1. Our investigations showed that the
      Mo requirement is met by normal intake. An intake of 150 micrograms kg-1 body
      weight may be toxic for humans. Therefore, people in Germany and Mexico are not
      endangered by Mo exposure.

PMID- 9659708
TI  - Feasibility study of the spectroscopic measurement of oxyhemoglobin using whole
      blood without pre-treatment.
AB  - A feasibility study was carried out to evaluate a chemometrics-enhanced
      measurement of oxyhemoglobin concentration in whole blood without pre-treatment
      by lysing cellular components in the sample. Conventional in vitro multi
      wavelength CO oximeters pre-process blood by sonication or detergent dilution to
      lyse blood cells to reduce light scattering. Two limitations result: (1) residual
      cell membrane fragments can seed surface biofouling and (2) dilution errors can
      occur. A full wavelength method using multivariate analysis in chemometrics was
      applied to correct the light scattering effect in the measurement of
      oxyhemoglobin concentration. Whole blood specimens were adjusted to different
      oxyhemoglobin concentrations with gas mixtures (N2, CO2 and O2). An Ocean Optics
      miniaturized spectrophotometer with a 100 microns pathlength optical cell was
      used for transmission measurements from 500 to 700 nm. Original spectra were
      smoothed and a second derivative transformation was performed to eliminate the
      baseline shift and slope changes from light scattering. Indirect calibration was
      applied to the second derivative spectra. Two-factor cross-validation by
      principle components regression on two sets of data showed r2 = 0.985 and 0.946
      between predicted oxyhemoglobin concentration and those measured by an AVL 912 CO
      oximeter with RSD = 3.85 and 6.83%, respectively. Error analysis gave s = 2.36 x
      10(-5) (RSD = 0.23%) on derivative absorbance for the spectrophotometer
      measurement alone. Specimen settling and specimen sampling gave imprecision on
      derivative absorbance of s = 6.17 x 10(-4) (RSD = 4.4%) and s = 4.52 x 10(-4)
      (RSD = 1.4%), respectively.

PMID- 9659707
TI  - Platinum concentrations in urban road dust and soil, and in blood and urine in
      the United Kingdom.
AB  - Increasing Pt concentrations from vehicle catalysts have been reported from a
      number of countries. Analysis of Pt and Pd in soils and road dusts taken from
      areas of high and low traffic flows in SE England show concentrations of Pt in
      the range < 0.30-40.1 ng g-1 and Pd in the range < 2.1-57.9 ng g-1. Higher
      concentrations of Pt are associated with high traffic densities. Samples taken
      from streets of lower traffic flows were found to contain the lower
      concentrations of the ranges. Pilot studies of Pt concentrations in blood and
      urine using ICP-MS have been carried out. Platinum concentrations in whole blood
      were: precious metal workers, 780-2170, mean 1263 pmol l-1 (0.152-0.423, mean
      0.246 microgram l-1); motorway maintenance workers, 645-810, mean 744 pmol l-1
      (0.126-0.158, mean 0.145 microgram l-1); Imperial College staff, 590-713, mean
      660 pmol l-1 (0.115-0.139, mean 0.129 microgram l-1). Platinum concentrations in
      urine in pmol Pt per mmol creatinine were: precious metal workers, 122-682, mean
      273 [0.21-1.18, mean 0.47 microgram Pt (g creatinine)-1]; motorway maintenance
      workers, 13-78, mean 33.7 [0.022-0.135, mean 0.058 microgram Pt (g creatinine)
      1]; Imperial College staff, 28-130, mean 65.6 [0.048-0.224, mean 0.113 microgram
      Pt (g creatinine)-1]. Detection limits were 0.03 microgram l-1 for both blood and
      urine. The possible health effects of increasing Pt in the environment are
      discussed. Platinum provides an excellent example of the significance of
      speciation in metal toxicity. Platinum allergy is confined to a small group of
      charged compounds that contain reactive ligand systems, the most effective of
      which are chloride ligand systems. Metallic Pt is considered to be biologically
      inert and non allergenic and since the emitted Pt is probably in the metallic or
      oxide form, the sensitising potential is probably very low. Platinum from road
      dusts, however, can be solubilised, and enter waters, sediments, soils and the
      food chain. There is at present no evidence for any adverse health effects from
      Pt in the general environment, particularly allergic reactions.

PMID- 9659709
TI  - Trace analysis of benzalkonium chloride on skin by flow injection ionspray mass
      spectrometry-mass spectrometry.
AB  - A method for the analysis of trace-level benzalkonium chloride has been
      established using flow injection ionspray mass spectrometry-mass spectrometry
      with multiple reaction monitoring. Quantification was carried out using an
      external standard based on peak area summation of each benzalkonium ion (C8, C10,
      C12, C14, C16 and C18) in the mass spectra. The multiple reaction monitoring
      technique provides additional specificity for identification and quantification.
      The quantification linear dynamic range was found to be 5.0-100.0 ng ml-1, the
      correlation coefficient > 0.999, and the detection limit 1.2 ng ml-1. The method
      was applied to quantify benzalkonium chloride on skin, which was sampled with a D
      SQUAME tape from skin surface and extracted from the tape with methanol.

PMID- 9659710
TI  - Effects of copper and zinc ions on the germicidal properties of two popular
      pharmaceutical antiseptic agents cetylpyridinium chloride and povidone-iodine.
AB  - The effects of copper and zinc ions on the rate of killing of Gram-negative
      bacterium Pseudomonas aeruginosa, Gram-positive bacterium Staphylococcus aureus
      and fungal yeast Candida albicans by antiseptic agents cetylpyridinium chloride
      and povidone-iodine (Betadine) were investigated. In the 48 test cases copper and
      zinc ions clearly potentiated the antiseptic agents in 28 (58.3%) cases and
      exhibited an improved (not clear potentiation) activity in 15 (31.3%) cases. In
      five (10.4%) cases there was no change in the antiseptics' antimicrobial
      activity. In general zinc potentiated the antiseptic agents more than copper. If
      an 'improved activity' was the only criterion for this study, then a more rapid
      antimicrobial effect was observed in 43 out of the 48 test cases, i.e., 90%.

PMID- 9659711
TI  - [Partial median sternotomy in H. A new approach for cardiac surgery].
AB  - PURPOSE: To present our results with the minimally invasive thoracotomy (MIT) in
      patients with valve disease and to describe a new type of thoracotomy. METHODS:
      Twenty-five patients with valve disease as the major cardiac problem were
      operated during a five month period. Two types of incisions were used: one in an
      inverted-T fashion and another in a H fashion. Fourteen patients were submitted
      to an inverted-T incision and eleven to a H incision. In 24% of the patients
      reoperation was being performed. RESULTS: The incisions ranged from 7.5 to 11 cm
      (mean 9.1 cm), mean ICU stay was 31 h and hospital stay 4.8 days. In all but one
      patient the operation could be adequately in performed through the MIT, in only
      one patient total sternotomy had to be performed. CONCLUSION: The MIT may have
      some advantages such as, better aesthetic results, less pain and more sternal
      stability. These factors may improve early extubation and decrease hospital stay.
      The H type incision allows an adequate exposition of the most central part of the
      chest and all heart valves with adequate exposure. This technique led to no
      complications during reoperations and we believe it to be as safe as the total
      sternotomy.

PMID- 9659712
TI  - [Acute myocardial infarction diagnosis. The value of serum myoglobin levels,
      compared with creatine kinase MB fraction].
AB  - PURPOSE: To compare the diagnostic performance of two traditional plasma markers
      of myocardial infarction (MI), creatine kinase (CK) and its MB fraction (CK-MB),
      with plasma myoglobin (Mgb) levels, for the diagnosis of MI. METHODS: From
      September of 94 to February of 95, in an observational, prospective, and non
      controlled fashion, 64 patients admitted to a cardiology emergency room (ER),
      with non-traumatic chest pain were studied. Patients presenting with more than 6
      h after the onset of symptoms, muscular trauma, cardiopulmonary resuscitation and
      renal insufficiency were not included. Definitive MI diagnosis was established if
      the patient had at least two of the three classic MI findings: ischemic chest
      discomfort longer than 20 min, electrocardiogram with necrosis (Q waves) and
      elevated CK and CK-MB levels. RESULTS: There were 18 patients with MI. The
      sensitivity for CK, CK-MB and Mgb were respectively 33%, 22% and 61%. The
      specificity was 85%, for CK, 95% for CK-MB and 97% for Mgb. The difference
      between Mgb and CK sensitivities was 28%, with a 95% confidence interval (CI)
      from -4% to 59%, the difference between Mgb and CK-MB sensitivities was 39%, (CI
      9% to 69%). The difference between Mgb and CK specificities was 13%, (CI 12% to
      14%) and the difference between Mgb and CK-MB specificities was 2%, (CI-5% to
      9%). CONCLUSION: In the studied population, Mgb was more sensitive than CK-MB for
      the diagnosis of MI with similar specificity and Mgb was more specific than CK
      for this diagnosis.

PMID- 9659713
TI  - [Early and late physiological effects of balloon mitral valvuloplasty].
AB  - PURPOSE: To evaluate the early and late cardiorespiratory responses after balloon
      mitral valvuloplasty. METHODS: Nine female patients aged 35 +/- 9 years with
      mitral stenosis, in class II or III (NYHA) underwent up-right ergoespirometric
      test, resting electrocardiogram and echocardiogram before, 3 to 5 days (early
      evaluation) and 8 to 12 months (late evaluation) after mitral valvuloplasty. All
      patients were treated with digitalis and diuretics. RESULTS: During late
      evaluation, 44% patients were in class II and 56% were in class I (NYHA). The
      resting heart rate decreased (87 +/- 11 bpm vs 85 +/- 7 bpm vs 75 +/- 9 bpm) and
      the number of steps increased (4 +/- 1 steps vs 5 +/- 2 steps vs 6 +/- 1 steps);
      the peak oxygen uptake improved only in the late evaluation (16 +/- 3 mL/kg/min
      vs 18 +/- 4 mL/kg/min vs 22 +/- 7 mL/kg/min). The anaerobic threshold, minute
      ventilation (VE) and ventilatory equivalent for oxygen showed no change. The
      heart rate (1st step: 124 +/- 18 bpm vs 112 +/- 13 bpm vs 87 +/- 15 bpm), O2
      uptake (1st step: 10 +/- 2 mL/ kg/min vs 8 +/- 2 mL/kg/min vs 8 +/- 2 mL/kg/min)
      and VE decreased during submaximal exercise in early and late phases. The mitral
      valve area decreased in the late evaluation (0.94 cm2 vs 1.66 cm2 vs 1.20 cm2).
      CONCLUSION: Although partial restenosis tended to occur in these patients, they
      improved the functional class and cardiorespiratory performance and
      cardiocirculatory load during submaximal exercise.

PMID- 9659714
TI  - [Effect of eggplant on plasma lipid levels, lipidic peroxidation and reversion of
      endothelial dysfunction in experimental hypercholesterolemia].
AB  - PURPOSE: To study the effect of egg plant on endothelium-dependent relaxation,
      and plasma lipids in hypercholesterolemic rabbits, and to assess influence of
      this plant on the malondialdehyde (MDA) content of LDL particles and the arterial
      wall. METHODS: Thirteen male rabbits were randomly assigned to control (C),
      hypercholesterolemic (H) and egg plant (E) treated groups (n = 10 each). The H
      and E rabbits were fed a diet supplemented with cholesterol (0.5%) and coconut
      oil (10%) for 4 weeks. In addition, group E received 10 mL of the fruit juice/day
      during the last 2 weeks. The animals were killed and the aorta removed to measure
      MDA content and the endothelium dependent relaxation responses. Total plasma
      cholesterol, VLDL, LDL, HDL and triglyceride levels were determined using
      commercial kits. MDA was quantified in native and oxidized LDL and in the
      arterial wall. RESULTS: After 4 weeks, the E group rabbits had a significantly
      lower weight, plasma cholesterol, LDL, triglyceride and aortic cholesterol
      content than group H(p < 0.05). The MDA content that was significantly increased
      in the LDL particles and in the arterial wall of H rabbits was reduced in the E
      group (p < 0.05). Endothelium-dependent relaxation were significantly higher in
      the E group compared H group rabbits (p < 0.05). CONCLUSION: In
      hypercholesterolemic rabbits egg plant juice significantly reduced weight, plasma
      cholesterol levels, aortic cholesterol content and the MDA concentrations in
      native-oxidized LDL and in the arterial wall and increased the endothelium
      dependent relaxations.

PMID- 9659715
TI  - [Body fat distribution, blood pressure and plasma lipids and lipoprotein levels].
AB  - PURPOSE: To study associations between FAT distribution and blood pressure levels
      and concentrations of lipids and lipoproteins, irrespective of body fat content
      and physical activity. METHODS: A sample of 62 subjects of both genders aging 20
      45 years-old was used in the study. The adipose tissue distribution was based on
      the waist-to-hip ratio (WHR). Body fat content was estimated by the body mass
      index (BMI), and physical activity was assessed by maximal oxygen uptake
      (VO2max). Partial correlation analyses were used to determine the strength of the
      associations. RESULTS: After correction for BMI there was a significant partial
      correlation between centripetal adipose tissue distribution and serum
      triglyceride, LDL-cholesterol levels, and blood pressure. However, controlling
      for VO2max, there was no significant association between WHR and any serum
      variable and blood pressure. CONCLUSION: The centripetal adipose tissue
      distribution, independent of body fat content, was related to lipid and
      lipoprotein plasma concentrations and to blood pressure levels in both sexes.
      Physical activity seems to be an important modifier of this relationship,
      emphasizing its role in the control of cardiovascular risk factors.

PMID- 9659716
TI  - [Effect of exercise duration on the magnitude and duration of post-exercise
      hypotension].
AB  - PURPOSE: Considering that exercise duration may play a role in post-exercise
      hypotension, we tested the hypothesis that a prolonged submaximal exercise would
      lead to a greater and longer blood pressure fall after exercise than a shorter
      exercise bout. METHODS: Experimental protocol-10 subjects were submitted to two
      cycle ergometer exercise trials (25 and 45 min) at 50% of VO2 peak. Control
      protocol-12 subjects rested in the sitting position for 45 min. Blood pressure
      (BP) was measured before (20 min) and after (90 min) rest or exercise bouts.
      RESULTS: Systolic BP decreased significantly after exercise and this reduction
      was greater and lasted longer after 45 min of exercise. Mean and diastolic BP
      decreased after exercise and they were significantly lower during the 45 min
      session. Control protocol--no change in BP was observed after resting condition.
      CONCLUSION: A longer exercise bout leads to a greater and longer post-exercise
      hypotension.

PMID- 9659717
TI  - [Stereology of the myocardium in young and aged rats].
AB  - PURPOSE: To determine the myocardial quantitative changes comparing young and
      aged animals by using the stereology. METHODS: Thirty rat hearts were studied (15
      rats aged 3 months and 15 other rats aging 15 months). The hearts were removed,
      weighed, fixed in 10% buffered formaldehyde solution, embedded in paraffin, cut
      in 7 microns thick slices and stained with HE and picro-sirius stains. In each
      group, we counted 15 random microscopic fields. The following parameters were
      studied: Vv (myocyte) and Vv(interstitium)(%) (the volume densities of the
      cardiac myocyte and interstitium, determined by the point-counting method), and
      Nv(myocyte) (1/mm3) (the numerical density of the cardiac myocytes, determined
      with the disector method). The total number of myocytes (N[myocyte]) and the mean
      volume of the myocytes (V[myocytes]) were also determined. The differences were
      tested by the Mann-Whitney test. RESULTS: Cardiac weight increased from 1.1 to
      1.7 g, the Vv(myocyte) decreased from 76.7 to 72.2%, the Vv(interstitium)
      increased from 23.3 to 27.8%. The Nv(myocyte) and the N(myocyte) decreased from
      14.76 x 10(4) to 6.19 x 10(4)/mm3 and 15.64 x 10(4) to 10.72 x 10(4) myocytes,
      respectively. Simultaneously, the V(myocyte) increased from 5.42 x 10(3) to 13.26
      x 10(3) mm3. These differences were statistically significant (p < 0.05).
      CONCLUSION: Myocardial changes, comparing young rats with aged ones suggest loss
      of myocytes (increased apoptosis?) with simultaneous myocyte hypertrophy.

PMID- 9659718
TI  - [Association of various measurements of obesity and the prevalence of
      hypertension].
AB  - PURPOSE: To evaluate the association between body mass index (BMI), waist-hip
      ratio and waist circumference with the prevalence of hypertension in a
      representative sample of 1088 adults of Porto Alegre (RS), Brazil. METHODS: In
      this cross-sectional survey, subjects were considered as having hypertension if
      they had systolic blood pressure > or = 160 mmHg or diastolic > or = 90 mmHg, and
      were considered obese if they had BMI > or = 27 kg/m2, or had a waist-hip-ratio >
      or = 0.95 cm (men) or 0.80 (women) or had a waist circumference > or = 96 (men)
      or 92 (women). RESULTS: Obesity defined by the BMI was associated with
      hypertension in both genders (RR 1.9, CI 1.0-3.2 in men; RR 2.2, CI 1.3-3.8 in
      women). The other indices were significantly associated with hypertension just in
      women. CONCLUSION: BMI > or = 27.0 kg/m2 was strongly associated with increased
      odds to have hypertension. Similar magnitude of the association with the other
      indices indicate their utility to estimate the risk of hypertension.

PMID- 9659719
TI  - [Meningococcemia complicated by myocarditis].
AB  - We report a case of a 26-year old man with meningococcemia complicated with
      myocarditis (ventricular dysfunction and myocardial ischemia), that required
      treatment for heart failure. Regression of myocardial dysfunction was observed
      six months after the infection.

PMID- 9659720
TI  - [Heart involvement in systemic amyloidosis. In vivo diagnosis].
AB  - This is the case of a 42 year-old male with systemic amyloidosis, probably
      primary, and heart involvement. Physiopathological and clinical aspects are
      described as well as the rarity of the diagnosis in vivo. The limited aspects of
      therapy are also described.

PMID- 9659721
TI  - [Anathomoclinical correlation (Case 1/98-Instituto do Coracao do Hospital das
      Clinicas-FMUSP)].

PMID- 9659722
TI  - [Use of transesophageal echocardiography in cardioversion of atrial
      fibrillation].

PMID- 9659723
TI  - Cost benefit vs. cost effectiveness--a new game plan for a new millennium?

PMID- 9659724
TI  - Musculoskeletal problems and driving in police officers.
AB  - The Occupational Health Department of a rural police force in the UK had concerns
      regarding sickness absence levels due to musculoskeletal problems, particularly
      in officers who drove as part of their job. It was decided to conduct an
      interview survey comparing two groups of police officers with differing levels of
      exposure to driving, recording sickness absence and prevalence data related due
      to musculoskeletal troubles. The results indicate that exposure to car driving,
      both in terms of distance and hours driven, had a significant effect on self
      reported low back trouble. Officers whose job mainly involved driving also
      experienced more low back trouble over the last 12 months than those whose job
      primarily involved sitting (not driving), standing and lifting tasks. Police
      motorcyclists had significantly higher prevalence figures for reported shoulder
      trouble than police car drivers.

PMID- 9659725
TI  - Progress of work career, retirement-orientation and health in middle-aged
      workers.
AB  - A lifelong work career has been stated to have an influence on a worker's health
      and ability to work. Nevertheless, the significance of the work career has been
      neglected in most retirement-studies. The aim of the present study was to
      describe the associations between progress of the work career, the retirement
      orientation, health and ability to work among aged workers. The data was obtained
      by a postal questionnaire and clinical examinations. The study group consisted of
      706 (70%) middle-aged urban persons (383 women and 323 men), who were 55 years
      old and who lived in northern Finland. The state of health and ability to work
      were significantly better among the work-oriented than among the retirement
      oriented workers and the health of the retired was the worst. Correspondingly,
      the state of health and ability to work were estimated to be better among the
      participants who advanced during their work career than among the other
      participants.

PMID- 9659726
TI  - Increases in body mass index and waist circumference as outcomes of working
      overtime.
AB  - This epidemiologic study was undertaken to determine whether working overtime is
      associated with anthropometric indices and serum lipids, risk factors for
      obesity, in white-collar workers. Non-management white-collar male workers were
      eligible. Body weight and height, waist circumference, skinfold thickness, serum
      total cholesterol and triglycerides were measured. Weight, height and waist
      circumference data obtained 3 years previously were also used. Lifestyle
      information was obtained by means of a self-administered questionnaire. Overtime
      hours correlated significantly with the 3-year change in body mass index (r =
      0.206, p < 0.0017) and waist circumference (r = 0.218, p = 0.0091), but not with
      either the most recent anthropometric indices or serum lipids. Overtime hours
      were also intercorrelated (r = 0.436, p < 0.0001) with dinner time. The present
      study suggested that working overtime is associated with the increases in BMI and
      waist circumference over a 3-year period although the associations were weak.
      Additionally, eating habits of those with working overtime might reflect an
      intervening effect on the anthropometric changes.

PMID- 9659727
TI  - Assessment of colour vision impairment in male workers exposed to toluene
      generally above occupational exposure limits.
AB  - We investigated colour vision impairment in 45 male workers occupationally
      exposed to toluene (mean value of toluene concentration in ambient air = 119.96
      ppm) and in 53 controls. Colour vision was evaluated by Lanthony-D-15 desaturated
      test and expressed as Age and Alcohol Intake Adjusted Colour Confusion Score
      (AACDS) or types of dyschromatopsia. Exposure was evaluated by measurement of
      toluene concentration in ambient air and blood, and hippuric acid and orthocresol
      determined in urine after the workshift. A statistically significant higher AACDS
      value was established in the exposed subjects compared to the controls (p <
      0.0001). There was no significant difference between AACDS values on Wednesday
      morning compared to Monday morning. In the exposed group AACDS significantly
      correlated with the concentration of toluene in ambient air, concentration of
      toluene in blood and the concentration of hippuric acid in urine after the
      workshift (all p < 0.0001). Dyschromatopsias were detected in both groups,
      although no significant difference between groups was established. In the exposed
      group concentration of toluene in ambient air, alcohol intake and age explained
      35.1%, concentration of toluene in blood, age and alcohol intake explained 19.9%,
      and concentration of hippuric acid in urine and age explained 19.2% of the
      variation in type III dyschromatopsia. Concentration of toluene in ambient air
      and age explained 28.3% of the variation in total dyschromatopsia, and
      concentration of hippuric acid and age explained 13.8%. In the control group, age
      and alcohol intake explained 19.6% of the variation in type III dyschromatopsia.
      In exposed workers a significant difference was found in the AACDS value compared
      to controls. However, no significant difference was found in the prevalence of
      colour vision loss in the yellow-blue and/or red-green axis. Based on the results
      of this study the authors conclude that the effect of toluene on colour vision
      can be chronic and that the possible reparation period in colour vision
      impairment is longer than 64 hours.

PMID- 9659728
TI  - Applicability of survey feedback for an occupational health method in stress
      management.
AB  - The main stressors in work organizations have been determined in the research on
      mental stress. This has prompted occupational health personnel to actively look
      for new tools in reducing stress. However, only a few workplaces have implemented
      action models for health promotion by reducing stressors. The aim of this project
      was to investigate the applicability of survey feedback for an occupational
      health method of stress management. The survey feedback process, which has been
      one of the main approaches in organization development, was applied for stressor
      reduction. The employee's commitment to the programme was confirmed by
      participation. The occupational health personnel were responsible for carrying
      out the programme. The project was carried out in selected departments of one
      factory of an international paper company. On the basis of the survey feedback,
      the departments made changes in their action models, environment and instruction
      and guidance systems. According to the follow-up in one department, the
      variability of work increased, and overall mental and physical strenousness
      decreased. The OH personnel shifted their working model towards more active co
      operation with the work units. Today the survey feedback is a routine method of
      the occupational health service of the company.

PMID- 9659729
TI  - Visualization of chronic neck-shoulder pain: impaired microcirculation in the
      upper trapezius muscle in chronic cervico-brachial pain.
AB  - This study pertains to the 71 patients who had received a diagnosis of cervico
      brachial pain syndrome after thorough clinical examination of a total series of
      300 patients, who had been referred to the National Insurance Hospital in Tranas
      because of chronic neck pain that interfered with their ability to work. Changes
      in trapezius muscle blood flow and EMG were examined and related to the anamnesis
      and physical findings. The microcirculation in the upper part of the right and
      left trapezius muscles was examined simultaneously by using optical laser-Doppler
      single-fibres after insertion into the muscle directly via the skin. Continuous
      recordings were made during stepwise increased static contraction determined
      electro-myographically. Signal processing was performed on-line by computer. MRT
      of the cervical spine was performed in 12 patients. None showed nerve root
      affliction. Ten showed a bulging intervertebral disc and two, a narrowed nerve
      hole (lateral stenosis). The muscle blood flow (LDF) was significantly lower in
      the most painful side compared with the opposite side in the group of 41 patients
      with predominantly unilateral pain (21 women and 20 men). A lowered blood flow
      was also found when the 21 females in this group was compared with a normal
      control group of 20 healthy women. The patients had lower rms-EMG and EMG mean
      power frequency (MPF) in the painful side compared with the opposite side. A
      further lowering of the MPF was observed with induced fatigue. It was concluded
      that the chronic neck pain in cervico-brachial syndrome can become visualized by
      the finding of lowered blood flow of the trapezius muscle which seems to be an
      expression of the chronic neck pain.

PMID- 9659730
TI  - Biological monitoring standards for industrial toluene exposure recommended for
      South Africa.
AB  - Coal combustion is used in many industrial processes in South Africa. The
      exposure of workers and the absence of international biological monitoring
      standards for toluene created a problem. A cross-sectional study on 100 workers
      indicated that the biological threshold for ortho-cresol:creatinine ratio
      reference value of < 1 mg/g could presently be used as a reference for non
      industrial human exposure while the < 2 mg/g rate is for worker exposure in an
      industrial environment at a coal combustion plant.

PMID- 9659731
TI  - The construction flagperson: a target for injury.
AB  - A road construction 'flagger' is a construction crew member whose responsibility
      it is to safely co-ordinate vehicle traffic through road worksites. Flaggers are
      suffering injuries and fatalities at the worksite as a result of being struck by
      moving vehicles, both construction and commuter. These incidents are largely
      preventable with a more defensive flagger training programme. A cross-Canada
      provincial survey of occupational health and safety organizations revealed no
      national co-ordination and standardization in flagperson training. Statistics
      concerning flagger injury and fatality are disjointed and incomplete, and as such
      are not useful for evaluating and validating training and job performance. We
      recommend a revisiting of flagperson training standards and that greater effort
      is taken in gathering data specifically on flagger injuries and fatalities.

PMID- 9659732
TI  - Quality management of occupational health services: the necessity of a powerful
      medical profession.
AB  - Over the past few years there has been a growing interest in quality management
      in occupational health services. In this article the central role of the medical
      profession in this area is highlighted from a personal point of view. It is
      argued that a powerful and active profession is needed as a countervailing power
      in the field of tension between employees and the company, and for balancing the
      interests of these two main clients. Therefore, the medical profession should
      develop a policy on quality and apply quality management on national and local
      levels to reach a high professional level. In this way the profession can
      maintain the clinical autonomy that is necessary to be a countervailing power.
      Elements of such quality management are national guidelines, local peer review
      and intercolleagual visitation. These activities must be incorporated in the
      quality management of the occupational health services unit.

PMID- 9659733
TI  - Occupational exposure to inorganic mercury vapour and reproductive outcomes.

PMID- 9659734
TI  - Cytokines and Chagas disease in mice.

PMID- 9659735
TI  - [Intertrigo in patients with lower limb lymphedema. Clinical and laboratory
      correlation].
AB  - Cutaneous lesions in the interdigital spaces are commonly seen in lymphedema
      patients and their prevention and suitable care is one of the cornerstones of any
      successful treatment, by preventing acute inflammations and additional worsening
      in limb volume and fibrosis. We obtained swab specimens from the interdigital
      area from 21 patients followed in the Lymphedema Unit of the Department of
      Vascular Surgery of the University of Sao Paulo; thirteen of them had lesions
      suggestive of tinea pedis. The pathological agent could be identified in 11 out
      of these 13 patients: fungal infection alone was responsible for seven lesions,
      Corynebacterium minutissimum for another two and both agents were isolated from
      two patients. Although two patients had evident clinical lesion of the skin, no
      fungal or bacterial species could be isolated. From the eight patients without
      interdigital lesions, Candida and Corynebacterium was found in one. We concluded
      that clinical examination has a high sensibility (84%) and specificity (91%) but
      the high prevalence of Corynebacterium minutissimum suggests that adequate
      treatment should follow careful laboratory examination.

PMID- 9659736
TI  - [Hyperdynamic circulation in Manson's hepatosplenic schistosomiasis].
AB  - Twenty two patients having indication for surgical treatment of portal
      hypertension due to hepatoesplenic schistosomiasis were prospectively studied.
      Each patient was submitted to preoperative monitoring with pulmonary artery
      catheterization. The results showed hemodynamic alterations characterized by an
      increase of cardiac index (4.50 +/- 0.96 l/min/m2) associated to a decrease of
      systemic vascular resistance index (1638.60 +/- 441.86 dyn.s/cm5.m2). The stroke
      index and all right and left cardiac work indeces were increased. The pulmonary
      artery mean pressure was increased (17.23 +/- 8.63 mmHg) and the pulmonary
      vascular resistance index was decreased (147.95 +/- 126.21 dinas.seg/cm5.m2). We
      concluded that hepatoesplenic schistosomiasis determines hyperdynamic systemic
      circulation, probably correlated with portosystemic shunt, and pulmonary
      hypertension.

PMID- 9659737
TI  - [Urinary excretion of vitamin A and thiobarbituric acid reactive substances in
      AIDS patients].
AB  - In the present investigation 28 serologically positive HIV-1 patients, 16
      patients with AIDS (< 200/mm3 CD4+ T lymphocytes) and 12 with HIV-1 (200 to
      500/mm3 CD4+ T lymphocytes) were studied. The Control Group consisted of 11
      healthy individuals. The occurrence of alterations in the anthropometric
      parameters were higher in AIDS patients, compared to HIV-1 and controls patients,
      indicating a greater level of malnutrition. All individuals in present study
      showed normal plasma vitamin A levels. Contrasting, urinary excretion of vitamin
      A were higher in the AIDS Group (0.23 +/- 0.20 mumol/l) than in the HIV Group
      (0.19 +/- 0.12 mumol/l) and considerably higher than in the Control Group (0.06
      +/- 0.05 mumol/l). Urinary excretion of TBARS also were higher in AIDS Group
      (3.34 +/- 2.65 mumol/l) compared to HIV (1.71 +/- 0.74 mumol/l) and Control Group
      (1.70 +/- 0.75 mumol/l). These results demonstrate a greater level of
      malnutrition and elevate excretion of vitamin A and SRATB in urine of AIDS
      patients. Therefore, monitoring of nutritional status, especially in relation to
      vitamin A is recommended for patients with HIV and AIDS.

PMID- 9659738
TI  - [Interpretation of the quantitative data of the computerized baropodometry in
      normal subjects].
AB  - The present work intended to test the validity of the quantitative datas provided
      by computerized baropodometry based in three comparisons: between static vertical
      force on the three regions of the foot and weight, between vertical force on the
      three regions of the foot during gait and weight, and between peak plantar
      pressure on the three regions of the foot and weight. It was used body weight
      because the calibration of the equipment is done in relation to the body weight
      of the patient. It was selected ten volunteers without foot pain complaints, age
      between 27-54 years old, 6 women and 4 men. The equipment used was the FSCAN
      version 1.821 (Teckscan, Boston MA), with new insoles. At the static assessment,
      the correlation between vertical force and weight was statistically significant
      only to the midfoot. At the assessment during gait the correlation between
      vertical force and weight was statistically significant for all regions of the
      foot and the correlation between peak plantar pressure and weight was
      statistically significant only to the midfoot. The clinical interpretation of the
      quantitative data provided by this exam must be done with caution due to uncount
      variables that are involved.

PMID- 9659739
TI  - [Hereditary angioedema: clinical and laboratory aspects of 7 cases].
AB  - Hereditary angioedema is caused by a defect in C1 inhibitor activity (C1INH). Its
      occurrence is rare and it is associated with an autosomal dominant mode of
      inheritance. We describe seven patients (4M:3F), age from 12 to 50 years old, who
      are affected by hereditary angioedema; four of them belong to the same family.
      The main clinical manifestations were: angioedema of face, hands and feet (6/7)
      and abdominal pain (2/7). No triggering factors were associated with symptoms in
      4/7 patients and trauma (2/7) and menses (1/7) were reported in the other three
      ones. One patient was submitted to laparotomy for partial intestinal resection,
      before diagnosis. Laboratory complement analysis revealed the absence of
      hemolytic function of complement, reduced C4 (6/7) and low C1INH levels. All
      patients received Danazol (100 mg/day) with clinical control. Hereditary
      angioedema has to be considered in the differential diagnosis of angioedema,
      since an early diagnosis of this immunodeficiency, leading to specific treatment
      in order to decrease the complications.

PMID- 9659740
TI  - [Carcinoid tumors of the common bile duct: report of a case].
AB  - The authors discuss an uncommon case in the literature of a carcinoid tumor of in
      the bifurcation of common hepatic duct. The tumor was surgically resected and the
      duct was reconstructed by Y of Roux's technic. The patient had a good evolution
      and no tumoral lesion was found in post operative exams during the last six
      months. The authors present a literature review and discuss diagnosis, treatment
      and prognosis.

PMID- 9659741
TI  - [Perforated gastric ulcer: an increasing neonatal ICU disease? Report of 4
      cases].
AB  - Between november 1994 and september 1995, there were 4 cases of premature infants
      in our Neonatal Intensive Care Unit (NICU) who developed gastrointestinal
      perforation and bleeding due to peptic ulcer and 3 died of this complication. In
      the first case, the neonate developed pneumoperitonium when weaning from the
      ventilator and was submitted to the operation with clinical diagnosis of
      Necrotizing Enterocolitis. Surprisingly, during the procedure, a perforated
      gastric ulcer was disclosed. Ever since, this NICU is aware of this diagnosis and
      try to better identify the possible risks factors. Asphyxia, prematurity, stress
      and situations where low gastrointestinal flow (asphyxia, exchange transfusion,
      pneumothorax, hemodynamic shock, cardiac arrest) were observed in almost every
      case. Treatment with dexamethasone or aminophilline was used in 3 of 4 cases and
      this potential serious side effect should be considered in all babies treated
      with steroids. The association of ranitidine (2 mg/kg 12/12 h) could not prevent
      the perforation in cases 1 and 3. Better understanding of physiopathology of the
      ulcer in this period of life and a effective preventable drug is still lacking.

PMID- 9659742
TI  - [Necrotizing fasciitis. Case report and review of literature].
AB  - Necrotizing fasciits (NF) is a rapidly progressive disease characterized by
      extensive necrosis of the fascia, skin, and subcutaneous tissue, with
      characteristical sparing of the underlying muscle. It is considered to be a rare
      entity and is associated with a high mortality rate since early recognition and
      treatment are not provided. Extensive surgical debridement of all necrotic
      tissues and appropriate antimicrobial treatment are the cornerstones for a
      successful treatment. We present a case of NF in a 36-year-old man and discuss
      it's pathophysiology, clinical manifestations and the best therapeutic choice for
      this potential life threatening disease.

PMID- 9659743
TI  - [Laparoscopic cholecystectomy in a patient with sickle-cell anemia].
AB  - Laparoscopic cholecystectomy has recently become a popular alternative to
      traditional laparotomy and cholecystectomy in the management of patients with
      gallbladder disease. Elective surgical treatment of cholelithiasis in patients
      with sickle cell anemia has been followed by frequent postoperative
      complications. We present a case of elective laparoscopic cholecystectomy in a
      patient with sickle cell anemia followed by severe postoperative complications
      related to the hematological disease.

PMID- 9659745
TI  - [Comparative analysis of PAC-I and PAC-II].
AB  - Comparison between the results of students' evaluation of the University of Sao
      Paulo Medical School with the results of the coordinators' evaluation of their
      own program is presented; 32 programs during 1996 were studied. In 50% of the
      cases, the students and professors evaluation were identical. In 28.1% of the
      cases, the evaluations made by students were higher than the professors'
      evaluation, mainly in clerkship. In 21.8% of the cases, the contrary took place
      mainly in the first to fourth year programs.

PMID- 9659744
TI  - [Tropical filarial pulmonary eosinophilia and its differential diagnosis].
AB  - The authors present a comprehensive review of Tropical Pulmonary Eosinophilia
      (TPE) of filarial etiology and describe its differential diagnosis with similar
      syndromes. Epidemiological, clinical, diagnostic, therapeutic and
      phisiopathological aspects are considered, with an emphasis on new advances in
      our knowledge of lymphatic filariasis and their implication for improved
      understanding of TPE and similar syndromes. A TPE-like syndrome, which is caused
      by intestinal helminth infections, occurs in filariasis-endemic and non-endemic
      areas alike. The authors suggest guidelines for interpreting epidemiological,
      clinical, laboratory, radiologic (including ultrasonographic) and therapeutical
      data and properly diagnosing TPE syndromes. This guidelines also should be useful
      for physicians in areas where filariasis is not endemic but to which patients
      from endemic area (e.g., Greater Recife-PE, Maceio-AL and Belem-PA) frequent
      migrate.

PMID- 9659746
TI  - [The "impact factor" and the impact of medical journals].
AB  - Original articles published in scientific journals are important parameters for
      committees when they evaluate academic promotions or research grant applications.
      The analysis usually tries to give each paper a qualitative/quantitative
      assessment. An article's citation by others is accepted as a fair estimate of the
      value assigned to its originality and importance. A main determinant of every
      citation index is the international relevance attained by the journal where the
      article appeared. The "impact factor" of journals enlisted in the mainstream
      literature, as defined by the Journal Citation Reports (ISI), is being used by
      many assessors worldwide. But this index appears to be an unfair unit of
      measurement for journals that, although included in the main international data
      bases, are published in non-English languages. Furthermore, some local journals
      that are not enlisted by the Institute for Scientific Information apply external
      peer review to select their publications. In contrast, those same journals may
      have great relevance for their contributing authors and a high impact in their
      readers. The Editor's proposal is to classify original articles published in
      biomedical sciences, clinical medicine and public health topics using a three
      steps scale: a low score to articles published in local journals that use the
      peer review system, even though they were not enlisted in international data
      bases; a higher score to articles published in journals included in the
      mainstream literature, without considering their "impact factors" as differential
      values; and the highest score to articles published in journals recognized as
      international leaders in biomedicine, general medicine or in the subspecialties.
      Therefore, mainstream journals published in non-English languages would not be
      discriminated from other journals having higher "impact factors" mainly due to
      their use of the English language.

PMID- 9659747
TI  - [Interleukin-8 levels in gastric biopsies of children colonized by Helicobacter
      pylori].
AB  - BACKGROUND: Helicobacter pylori produces a gastric mucosal inflammation
      characterized by neutrophil infiltration, due to the liberation of interleukin-8.
      AIM: To measure interleukin-8 levels in gastric mucosa samples from children
      colonized by H. pylori. PATIENTS AND METHODS: Thirty one children that required
      an upper gastrointestinal endoscopy for diagnostic purpose were studied. Antral
      biopsies were obtained for pathological study, H. pylori detection using CLO-test
      and interleukin-8 determination by ELISA. RESULTS: Nine children were not
      infected with H. pylori. Of these, six had a pathologically normal gastric mucosa
      and three had a mild chronic gastritis. Twenty two children were infected by H.
      pylori and all had a chronic gastritis with activity signs in 13. Mucosal
      interleukin-8 was higher in infected than in non infected children (59.7 (range
      6.1-379.7) and 15.8 (range 3.9-104.1) pg/mg respectively p = 0.029). Colonized
      children with an active chronic gastritis had higher interleukin-8 levels than
      those with inactive gastritis (84.4 (range 33.3-379.0) and 26.8 (range 6.1-372.6)
      pg/ml respectively p = 0.04). CONCLUSIONS: Stomach colonization by H. pylori is
      associated with higher mucosal levels of interleukin-8. This phenomenon probably
      plays a role in the genesis and intensity of gastric mucosal inflammation in
      children.

PMID- 9659748
TI  - [Calcium intake and bone density in menopause. Data of a sample of Chilean women
      followed-up for 5 years with calcium supplementation].
AB  - BACKGROUND: A low calcium intake is considered a risk factor for osteoporosis.
      AIM: To measure calcium intake and its relationship to bone mineral density in
      postmenopausal women and to assess the long term changes in bone mineral density
      after calcium supplementation. PATIENTS AND METHODS: In 80 postmenopausal women,
      older than 41 years of age, calcium intake was assessed using dietary inquiries
      and bone mineral density was measured using a double beam radiological
      densitometer. Twenty-four randomly selected women received a daily calcium
      supplementation of 500 mg during five years and their bone mineral density was
      measured at 1, 3 and 5 years. RESULTS: Initial calcium intake was 745 +/- 37
      mg/day, and it did not change in the five-year follow up. There was no
      relationship between bone mineral density and calcium intake. In supplemented
      women, bone density did not change significantly at year one. At year three, a
      significant reduction was observed in the spine (-4.2%), Wards triangle (-4%) and
      whole body mineral content (-1.14%). At year five, there was a significant
      increase in bone density at the spine, femoral neck and Wards triangle as
      compared with year three, but not with baseline measurements. No significant
      differences after supplementation were observed between women with initial
      calcium intake of less than 500 mg/day or over this value. CONCLUSIONS: Calcium
      intake in urban Chilean postmenopausal women is below recommendations and stable
      over time. Calcium intake and bone mineral density after the menopause are not
      correlated. A 500 mg/day calcium supplementation during five years is associated
      with a late reversal of the postmenopausal bone-losing trend.

PMID- 9659749
TI  - [Measurement of low levels of plasma renin activity. A methodological
      improvement].
AB  - BACKGROUND: The present method to measure plasma renin activity is cumbersome and
      imprecise, factors that limit its clinical application. AIM: To assess the
      importance of blood sampling conditions and the usefulness of increasing
      incubation time to measure plasma renin activity at low levels. PATIENTS AND
      METHODS: Twenty hypertensive patients, 14 female, aged 14 to 76 years old, were
      studied. Two blood samples were obtained after a 10 min rest in the sitting
      position and after a 30 min rest in supine position. One blood sample of each
      condition was sent to the laboratory at room temperature and the other sample was
      sent refrigerated. Angiotensin I concentration was determined after 3 h of
      enzymatic incubation at 37 degrees C and, in subjects with an activity of less
      than 1 ng/ml/h, after 18 h of incubation. RESULTS: No significant differences in
      plasma renin activity were observed between the samples obtained with different
      rest times or different transportation methods. In people with low plasma renin
      activity, the 18 h enzymatic incubation reduced the lower detection from 0.3 to
      0.014 ng/ml/h and the coefficient of variation from 14.4 to 3.2%. CONCLUSIONS: A
      simplified blood sampling method does not change plasma renin activity values,
      and the longer enzymatic incubation in people with low plasma renin activity
      improves both the sensitivity and accuracy of the determination.

PMID- 9659750
TI  - [Biopsy and endoscopic prospective study of the prevalence of intestinal
      metaplasia in the gastroesophageal junction in controls and in patients with
      gastroesophageal reflux].
AB  - BACKGROUND: The classic diagnosis of Barret esophagus is based on the finding of
      three of more cm of distal esophagus covered by specialized columnar epithelium.
      However, at the present time, it is based on the presence of intestinal
      metaplasia in the junction of squamous-columnar mucosae. AIM: To assess the
      prevalence of Barret esophagus using endoscopic and pathological criteria in
      healthy subjects and in individuals with gastroesophageal reflux. PATIENTS AND
      METHODS: One hundred thirty nine controls and 372 patients with symptoms of
      gastroesophageal reflux subjected to an upper gastrointestinal endoscopy were
      studied. Patients with Barret esophagus were classified as having a "mini Barret"
      when the pathological presence of intestinal metaplasia was the only finding. A
      "short Barret esophagus" was diagnosed when less than 3 cm were covered with
      fingerings of mucosal substitutions and "extensive Barret esophagus" when more
      than 3 cm of esophageal mucosa were substituted. RESULTS: Two percent of
      controls, 12.4% of patients with gastroesophageal reflux without esophagitis and
      11.7% of such patients with esophagitis had intestinal metaplasia in the
      gastroesophageal junction. Patients with Barret esophagus were older than the
      rest of patients. "Short Barret esophagus" is six times more frequent than
      "extensive Barret esophagus". Esophageal erosions, peptic ulcers and stenosis
      were more frequent in patients with extensive Barret esophagus. The prevalence of
      dysplasia was similar in all types of Barret esophagus. CONCLUSIONS: Intestinal
      metaplasia was very infrequent in control patients. In subjects with
      gastroesophageal reflux, classic endoscopic diagnosis may miss up to 80% of
      patients with Barret esophagus. Thus, gastroesophageal junction biopsies must be
      obtained in all patients with symptoms of gastroesophageal reflux.

PMID- 9659751
TI  - [Patterns of sexual behavior in Chilean women].
AB  - BACKGROUND: Sexuality has an individual connotation, is influenced by biological,
      environmental and cultural factors and is present throughout all life. AM: To
      assess the sexual behavior of a group of Chilean women. SUBJECTS AND METHODS: A
      specially devised inquiry was applied to 301 women, aged 20 to 70 years old, that
      consulted in a medical service. RESULTS: Seventy seven percent of women were
      sexually active. These figures ranged from 80% of women aged 40-44 years old to
      40% of women over 60. Sixty percent of women living together, 53.7% of single
      women, 65.6% of divorced women, 94.2% of married women and 100% of widows were
      sexually active. Women aged 25 to 29 years old had a mean of 8.4 relations per
      month compared with 3.3 relations among women older than 55. The frequency of
      sexual intercourse was higher in women living together and lower in widows. The
      mean age at the first intercourse was 20.6 +/- 4.5 years. Ninety three percent
      had experienced sexual desire and the percentage of satisfactory sexual relations
      does not change with age. Less educated women had a lower frequency of orgasms.
      CONCLUSIONS: Age and legal status of women are related to their sexual behavior
      and less educated women have a less satisfactory sexual life.

PMID- 9659752
TI  - [Radiofrequency ablation of right accessory pathways].
AB  - BACKGROUND: Accessory pathways are muscular connections between auricles and
      ventricles, present in different points of mitral and tricuspid annuluses. These
      pathways participate in 50% of paroxysmal supraventricular tachycardias and the
      definitive cure of the arrhythmia is their ablation. AIM: To report our
      experience in patients with right accessory pathways. PATIENTS AND METHODS: Fifty
      consecutive patients treated between 1990 and 1996 are reported. Eight had a
      history of syncope, two had a diagnosis of Ebstein disease and 36 had a pre
      excitation in the surface electrocardiogram. RESULTS: Fifty four accessory
      pathways were identified, since four patients had two pathways. Twenty four
      pathways were posteroseptal, 15 were lateral, 9 were medioseptal and 6 were
      anteroseptal. One patient had also a nodal reentry tachycardia. Fulguration was
      attempted in 39 patients and it was finally successful in 32. Three patients
      required more than one session. There were six relapses and all were successfully
      ablated in a second session. A mean of 28 radiofrequency applications were done
      (range 1-76), mean laboratory time was 6 hours and mean radioscopy time was 70
      min. Four patients had a transient atrioventricular conduction blockade.
      CONCLUSIONS: Radiofrequency ablation of accessory pathways has a high degree of
      success and a low rate of complications.

PMID- 9659753
TI  - [Thyroid function in a population with an extra iodine intake].
AB  - BACKGROUND: After 20 years of iodine salt fortification, the prevalence of goiter
      has decreased significantly in the rural area of Pirque, central Chile. In this
      location, equipment has been installed that efficiently and economically adds 0.5
      mg of elemental iodine per liter of water to render it potable. AIM: To study
      thyroid function and urinary iodine excretion in school age children of this
      zone, after two years of extra iodine intake. MATERIAL AND METHODS: One hundred
      thirty four children aged 6 to 12 years old were examined. In 56 randomly chosen
      children a morning urine sample was obtained to measure iodine excretion. In 45
      children without goiter, a blood sample was drawn to measure TSH and thyroxin.
      RESULTS: In nine children (7%) a diffuse goiter was found. Median urinary iodine
      excretion was 158 micrograms/dl. Thyroxin and TSH levels were within normal
      limits (8.4 +/- 1.1 micrograms/dl and 2.2 +/- 1.5 microU/ml respectively). During
      the period of iodine water supplementation there were 47 births in the zone. All
      newborns had normal TSH values and none had goiter. CONCLUSIONS: When present
      results are compared with the period before water iodination (when the prevalence
      of goiter was 9.6% and mean urinary iodine excretion was 57.6 micrograms/dl), it
      can be concluded that extra iodine intake in this rural population has not caused
      additional thyroid problems.

PMID- 9659754
TI  - [Chronic hemodialysis in children].
AB  - BACKGROUND: The final objective of every children that is admitted to a program o
      hemodialysis of peritoneodialysis is to receive a renal graft. AIM: To report the
      experience in pediatric hemodialysis in two pediatric hospitals in Chile that are
      reference centers for renal transplantation. PATIENTS AND METHODS: Sixty
      patients, 55% female, aged 2 to 15 years old, admitted to the dialysis and
      transplant program since 1987, with a creatinine clearance of less than 20
      ml/min/1.73 m2, were studied. RESULTS: Twenty percent of children were less than
      5 years old at the moment of admittance to the program and 3.3% weighed less that
      10 kg. Etiologies of end stage renal disease were glomerulopathies in 33.4%,
      reflux nephropathy in 27.7%, obstructive uropathy in 13.3%, hypoplasia/dysplasia
      in 10%, hereditary problems in 8.3% and vascular disorders in 5%. Eighty six
      percent of patients were dialyzed less than 2 years and 5% more than 4 years.
      Fifty percent had received prior medical treatment, 5% had been treated with
      intermittent peritoneal dialysis, 5% with chronic ambulatory peritoneal dialysis
      and 20% presented as a terminal renal failure. Sixty two percent received a renal
      graft, 25% is still on hemodialysis, 3.3% switched to chronic ambulatory
      peritoneal dialysis, 3.3% had a recovery of renal function and 6.7% died being on
      hemodialysis. Arterio-venous fistulae were the vascular accesses in 75% of
      patients, double lumen catheters in 50% and vein grafts in 5%. Malfunctioning or
      infections were the main complications of arterio-venous fistulae, accounting for
      30% of hospital admissions. CONCLUSIONS: The availability of new vascular
      accesses and new hemodialysis machines specially designed for children, along
      with specially trained health care personnel, should reduce the mortality and
      complication rates of hemodialysis in this age group.

PMID- 9659755
TI  - [Education of patients with rheumatoid arthritis. Assessment of a survey of
      interests].
AB  - BACKGROUND: The congruence of interests between health care providers and clients
      is essential if subjects with chronic diseases will be educated. AIM: To assess,
      in patients with rheumatoid arthritis, those fields in which they would like to
      receive education. PATIENTS AND METHODS: Eighty eight patients with rheumatoid
      arthritis were surveyed about the topics in which they would like to be educated.
      The inquiry included medical aspects, handicap overcoming, social issues and
      labor aspects. RESULTS: Eighty two percent of patients were interested in medical
      aspects, 77% in social issues and 71% in handicap overcoming. Eighty three
      percent of patients with greater handicaps preferred handicap overcoming, 75%
      social aspects and 74% medical aspects. Younger patients had a greater interest
      in labor aspects, those with a recently diagnosed disease were interested in
      their legal rights and those with a prolonged disease wanted information about
      self help groups. CONCLUSIONS: The greater educational interests of patients with
      rheumatoid arthritis were on medical aspects. However, those impaired by the
      disease were interested in handicap overcoming. Age and duration of the disease
      also influenced the educational interests of patients. Thus, education in these
      patients must be individualized.

PMID- 9659756
TI  - [Septic phlebitis: origin of severe septic condition].
AB  - We report two patients, an 82 years old female and a 71 years old male, who had a
      severe sepsis with positive blood cultures for Staphylococcus aureus and a
      superficial phlebitis as the only probable focus. In both the diagnosis of septic
      phlebitis was reached and an emergency phlebotomy was performed under local
      anesthesia. The clinical response was satisfactory and the pathological
      examination of excised veins showed an acute exudative leukocytic
      thrombophlebitis.

PMID- 9659757
TI  - [MALT lymphoma of the bladder: report of a case].
AB  - Primary malignant lymphomas of the bladder are infrequent. We report a 70 year
      old woman presenting with hematuria, dysuria, malaise and a 5 kg weight loss.
      Pelvic ultrasound examination showed a 8 x 8 x 8 cm solid and cystic mass
      adjacent to the bladder and uterus. Cystoscopic biopsy disclosed a low grade B
      cell non Hodgkin lymphoma. She was treated with 6 cycles of chemotherapy with
      disappearance of the mass. Two years after admission, the patient is free of
      disease.

PMID- 9659758
TI  - [Information and technological development in the clinical laboratory].
AB  - Internet/world wide web is at the present time, one of the greatest sources of
      information, knowledge, reference materials, educational and training programs
      for the general population and specially for professionals of clinical
      laboratories. New equipment, methodologies and products have produced a profound
      change in the organization and operation of clinical laboratories. This article
      reviews the importance that these changes have in the efficiency and quality of
      clinical laboratories.

PMID- 9659759
TI  - [Duration of adjuvant treatment with tamoxifen in patients with resectable breast
      cancer].
AB  - Tamoxifen administered in patients after breast cancer surgery is one of the most
      effective adjuvant treatments in this pathology. A large number of randomized
      studies including thousands of patients allowed to quantify the treatment
      benefits in terms of recurrence, contralateral breast cancer and overall survival
      rates. The treatment is generally given for more than 2 years. However, the
      optimal treatment duration is unknown. Uncertainties appeared when adverse
      effects were described after some years of treatment (e.g. a higher incidence of
      endometrial adenocarcinoma). New ongoing multicentric trials will clearly define
      in the next years the optimal duration of this adjuvant treatment.

PMID- 9659760
TI  - [Medical care costs for HIV-positive and AIDS patients in four hospitals in
      Santiago, Chile].
AB  - BACKGROUND: Medical care of HIV infected and AIDS patients may represent an
      important economical burden for public hospitals. AIM: To assess direct and
      indirect costs of medical care for HIV infected and AIDS patients in public
      hospitals of the Metropolitan Region of Chile. MATERIAL AND METHODS: Between
      August 1994 and February 1995, information about outpatient and hospitalized
      medical care of 417 HIV infected patients was gathered (representing
      approximately 16% of the seropositive population). Patients were divided as
      having or not having AIDS. The latter were those included in groups I, II, III
      and category C2 of group C (group 4). The cost of medications, procedures and
      examinations of these patients was calculated. RESULTS: Thirty six percent of
      studied patients had AIDS. The annual cost of care for AIDS patients was US$3760
      compared to US$1450 for HIV infected patients without AIDS. Medications
      represented 75% and 65% of total costs in patients with and without AIDS
      respectively. The figures for examinations and procedures were 17% and 22% and
      for medical attentions were 7.5% and 8.8% respectively. CONCLUSIONS: Medical care
      of patients with AIDS has higher costs than that of HIV infected patients without
      AIDS. Thus, the retardation of the progression of the disease would have social,
      humanitarian and economical benefits. Our costs are similar to those of other
      countries with a similar level of economic development.

PMID- 9659761
TI  - [Comments on the fate of a manuscript after being submitted to a scientific
      journal].

PMID- 9659762
TI  - [Acute pulmonary edema associated with hydrochlorothiazide. Experience in a rural
      hospital of Chiloe, Chile].

PMID- 9659763
TI  - The erratic path to breast cancer screening in New Zealand.

PMID- 9659764
TI  - Varicella-zoster virus infection in Australia.
AB  - OBJECTIVE: To determine the epidemiology of varicella-zoster virus (VZV)
      infection in Australia using currently available data sources. DESIGN: Analysis
      of national death data (23 years), congenital and neonatal cases (one year) and
      attendances at sentinel general practices (two years); hospital admissions in NSW
      and SA (six years); serological studies in 1995 involving antenatal clinics in
      Sydney and Brisbane and child-care centre staff and refugees in Sydney; and case
      ascertainment in 1995 in South Western Sydney among public hospital staff, child
      care centre staff and the community. RESULTS: In Australia, there have been an
      average of 3.5 deaths from chickenpox (mostly children) and 11 from herpes zoster
      (mostly older people) each year since 1980. The crude death rate for chickenpox
      has declined (p > 0.05). In 1995, there were 14 cases of neonatal and two of
      congenital varicella. Average annual admission rates for NSW and SA showed 1,200
      hospital bed-days used for chickenpox, more than 20% with complications, and more
      than 7,300 bed days for zoster; annually more than 880 in-patient admissions were
      complicated by VZV. Most people encounter the virus in their first 15 years, but
      some remain susceptible into their 20s; 25% of cases and 37% of hospital
      admissions for chickenpox occur in people > or = 15 years of age. CONCLUSION: VZV
      infection involves people of all ages. It causes substantial morbidity and
      mortality, particularly at the extremes of life. The death rate from chickenpox
      but not zoster has fallen since the introduction of acyclovir in the 1980s.
      Surveillance of VZV infection must be given priority once vaccines become
      available, to monitor changes in morbidity and mortality.

PMID- 9659765
TI  - Incidence of hospital-treated traumatic brain injury in an Australian community.
AB  - This paper reports findings from an incidence study of head trauma in a defined
      population. In the North Coast Health Region of NSW, 1,259 subjects with head
      trauma were admitted to hospitals in a 12-month period in 1988. Direct
      examination of the medical records confirmed brain injury in only 413 of these
      cases, corresponding to an annual incidence of approximately 100/100,000 resident
      population. Although most injuries (62.2%) were mild, 38% were serious (either
      moderate, 20.3%, or severe, 13.6%; and 3.9% died after admission to hospital).
      Severe brain injury represented an annual incidence of 12/100,000 resident
      population. Road traffic accidents accounted for a higher proportion of injuries
      in the severe group in comparison with the other injury groups. Methodological
      issues involved in case ascertainment of brain injury are discussed.

PMID- 9659766
TI  - Structure of family planning in Samoa.
AB  - Increasing family planning acceptance and efficacy is considered a key public
      health issue in many Pacific island nations. To assess the structure of family
      planning acceptance in Samoa, structured interviews were conducted with 155
      reproductive age women from seven villages in both rural and urban settings. The
      survey data show accord with returns on contraceptive use from Samoan clinics,
      and demonstrate that awareness and use of contraception have increased markedly
      in the previous decade but desired family size remains high in younger women. A
      notable feature of the Samoan women's contraceptive experience is the lack of
      diversity of reported contraceptive behaviours and attitudes based on age, urban
      versus rural residence, and education.

PMID- 9659767
TI  - Environmental investigation of a legionellosis outbreak in western Sydney: the
      role of molecular profiling.
AB  - This investigation used DNA profiling in an attempt to identify the environmental
      source of a community outbreak of 11 cases of Legionnaires' disease. Nine of
      these cases were culture positive and a single strain (DNA profile) of Legionella
      pneumophila serogroup 1 was isolated from eight cases. Spot water samples were
      collected from 51 cooling towers implicated by case exposure histories; this same
      strain was isolated from four towers at three separate locations up to 6 km
      apart. None of these locations had been frequently implicated by case histories.
      Because we did not perform an analytic epidemiological investigation, we were
      unable to identify a single environmental source for the outbreak. It is also
      possible that this outbreak was multifocal. The use of molecular profiling should
      not overshadow the importance of epidemiological methods in these environmental
      investigations. More data is needed regarding the prevalence, distribution, and
      clinical significance (virulence) of environmental L. pneumophila strains. This
      would aid interpretation of molecular profiling used in investigations of
      community legionellosis outbreaks.

PMID- 9659768
TI  - Changing pattern of delays in reporting AIDS diagnoses in Australia.
AB  - To accurately monitor and predict the progress of the HIV/AIDS epidemic, it is
      important to adjust reported AIDS counts for reporting delays. This requires
      estimation of the reporting delay distribution. This paper aims to use a
      statistical model to identify the main factors influencing reporting delays in
      Australia and to adjust reported incidence data for these delays among cases of
      AIDS diagnosed from 1993 and reported before 30 June 1997. Reporting delays were
      found to vary significantly across states/territories. The influence of calendar
      time of diagnosis was also significant, with an overall trend toward longer
      delays over time. AIDS cases diagnosed in the fourth quarter of a year were
      reported significantly more quickly than those diagnosed in the first or third
      quarters. No significant differences were found due to sex, age and HIV exposure
      category, except people with haemophilia, in whom AIDS cases appeared to be
      reported more slowly. After adjusting for under-reporting and reporting delay, we
      found that the AIDS incidence in Australia was declining from about 1000 cases
      per year in 1994 to about 760 cases per year in 1996.

PMID- 9659769
TI  - The cost-effectiveness of home assessment and modification to reduce falls in the
      elderly.
AB  - Injury sustained through falling is a significant risk for the elderly and a
      significant burden on the health service. Although many risk factors have been
      detected and interventions proposed, there remains limited evidence concerning
      the cost-effectiveness of fall prevention. This study addressed the cost
      effectiveness of a home assessment and modification program hypothesised to
      reduce risk of falling for the independent elderly. Due to a lack of direct
      clinical trial evidence concerning such an intervention, a decision analytic
      model was developed to simulate the potential costs and outcomes of the
      intervention. The model was developed using available published literature
      concerning injury in the elderly, focusing on Australian data where possible.
      Cost-effectiveness was estimated as the cost per fall prevented and cost per
      injury prevented. Over a one-year period, the incremental cost of introducing the
      intervention was $172 per person, resulting in an incremental cost per fall
      prevented of $1,721 and cost per injury prevented of $17,208. Over a 10-year
      period, the intervention resulted in a cost saving of $92 per person (i.e.
      dominance, with cost savings in addition to reduced falls and injuries). This
      analysis indicates that there is potential for considerable benefit to be gained
      from this intervention, in terms of less morbidity, fewer hospitalisations and,
      possibly, improved quality of life. However, these results are based on a model
      constructed from various data sources and assumptions so, although results are
      indicative, further research is required to provide firm data before definitive
      policy conclusions and recommendations may be made.

PMID- 9659770
TI  - Vaccine preventable diseases and immunisations: a qualitative study of mothers'
      perceptions of severity, susceptibility, benefits and barriers.
AB  - This study investigated mothers' perceptions of vaccine-preventable diseases and
      associated vaccines in terms of perceived susceptibility, severity, benefits and
      barriers. A purposive sampling strategy was used to choose mothers whose only or
      youngest child was completely, incompletely (behind the recommended immunisation
      schedule) or partially (parents chose or advised not to have a specific
      immunisation) immunised or had no immunisations. Semi-structured interviews found
      that complete immunisers believed the risk of vaccines was lower than the risk
      from disease and that the likelihood of contracting many of these diseases was
      low. Incomplete immunisers perceived vaccines to be less effective in preventing
      disease and were often confused about which diseases the vaccines would protect
      against. Non-immunisers were more concerned about unknown, long-term side effects
      of vaccines than the diseases. Many mothers who did immunise believed that
      preventing diseases was not always possible and for diseases such as measles,
      mumps and rubella, it was not always necessary nor desirable. Vaccines were
      perceived as placing stress on the immune system rather than strengthening it.
      Important themes relating to barriers to the decision to immunise were a lack of
      'balanced', detailed information and poor communication between health providers
      and parents. The major barrier to timely, age-appropriate immunisations was the
      occurrence of minor illnesses in the target child or the family. This study found
      that many mothers were balancing the risks of immunising with the risks of not
      immunising and this must be taken into account, along with factors such as
      difficulties in obtaining immunisations.

PMID- 9659771
TI  - Safe driving education programs at school: lessons from New Zealand.
AB  - The self-reported driving and passenger behaviours of senior high school students
      in Auckland, New Zealand, were assessed prior to and about four months after a
      school-based program for driver education. The intervention group (n = 176)
      received a program of 10, one-hour sessions dealing with knowledge, attitudes and
      judgements relating to safe driving. A control group (n = 146) did not receive
      any formal driving safety education. Analyses of pre-treatment and follow-up
      questionnaire responses revealed that both the intervention and control groups
      showed significant improvements in knowledge about safe driving over time. Males
      reported more risky attitudes and behaviours than females throughout the study.
      There were no significant differences between the intervention and control groups
      on any measures. In discussing these findings, particular attention is paid to
      the program content and the social context in which such interventions are
      carried out.

PMID- 9659772
TI  - Bicycle injuries: road trauma is not the only concern.
AB  - Data on bicycle injury presentations at a public hospital emergency department
      for 1991-95 inclusive were analysed to determine the nature and extent of bicycle
      injuries in the community. There were 599 bicycle injury presentations during the
      study period, representing more than 2.0% of all injury-related presentations to
      the emergency department. The main outcome measures were severity and type of
      injury. Distribution by gender, age, helmet use (1991 and 1992 only), location
      and mechanism was examined. Rider-only injuries (falls or collisions with
      stationary objects) accounted for 79.3% of all presentations with only 5.2% due
      to collisions on a public road or footpath with other moving traffic. Of all
      injuries where a location was determined, 61.6% occurred in off-road locations.
      There was little difference in the overall proportions of hospital admissions
      from injuries on-road (12.4%) and off-road (9.0%). Cyclists injured in on-road
      collisions with traffic had a higher proportion of hospital admissions (40.0%)
      than those injured on-road by other mechanisms (7.6%). Children under 10 years of
      age who had been riding without a helmet suffered a much higher proportion of
      injuries to the head (53.2% of all injuries) than older cyclists riding without a
      helmet (19.4%). The majority (83.1%) of head injuries in children under 10 years
      of age occurred off-road and helmet use was lowest in this group (28.6%). Given
      previous evidence that helmet use can prevent head injuries, strategies to
      increase helmet use among cyclists, particularly young children, while riding
      both on and off-road, should be given a high priority. Rider-only injuries are
      also an important public health issue.

PMID- 9659773
TI  - Validity and reproducibility of a self-administered food frequency questionnaire
      in older people.
AB  - This study assesses the validity and reproducibility of a 145-item self
      administered food frequency questionnaire (FFQ) in a representative older
      population aged 63 to 80. Semi-quantitative FFQs were completed by 89% of 3,654
      residents attending a community-based eye study in Sydney, Australia. The FFQ's
      validity was assessed against three, four-day weighed food records (WFRs)
      completed four months apart by 79 people. A further 152 subjects completed a
      repeat FFQ about a year after the baseline FFQ, of whom 131 completed a second
      repeat FFQ about six weeks later. Both short and long-term reproducibility of the
      FFQ were assessed using data from these subjects. Comparison of the FFQ with the
      average of the three, four-day weighed food records resulted in energy-adjusted
      Spearman correlations above 0.5 for most of the nutrients. The proportion of
      subjects correctly classified to within one quintile category for each nutrient
      intake ranged from 57% for zinc to 82% for vitamin C. with most nutrients
      correctly classified within one quintile for about 70% of subjects. Quadratic
      weighted kappas were reasonable, between 0.3 and 0.5 for most nutrients. The FFQ
      was highly reproducible in the short term, with correlations for most nutrients
      about 0.70 to 0.80 and acceptably reproducible in the longer term, with
      correlations mostly 0.60 to 0.70. The results verify that it is possible to use
      relatively simple, but comprehensive, self-administered FFQs to study nutrient
      exposures in large-scale epidemiological studies of the elderly and to expect
      reasonably high FFQ response rates.

PMID- 9659774
TI  - Health indicators and risks among people experiencing homelessness in Melbourne,
      1995-1996.
AB  - During the study's first stage, 284 homeless people from crisis and long-term
      accommodation sites were surveyed using stratified, systematic sampling. The
      second stage involved a survey of a convenience sample of 100 homeless people
      from squats and the streets. Participants completed a questionnaire, Mantoux
      testing was performed and blood taken for gamma-interferon assay, liver and renal
      function tests. The group's health status was poor, with 72% experiencing medical
      conditions in the preceding two years and 77% symptoms in the month prior to
      interview. Bronchitis, asthma and gastroenteritis were the most commonly reported
      conditions; productive and persistent coughing, shortness of breath and wheezing
      the commonest symptoms. Twenty-one per cent had Mantoux reactions 15 mm or
      greater, 28% a raised GGT and 19% a raised ALT. Seventy-seven per cent smoked,
      74% were current drinkers, 28% had injected drugs at some time in their lives and
      14% were regularly injecting drugs. Forty-four per cent had experienced mental
      illness, 49% of whom reported depression and 15% schizophrenia. Homeless people
      in Melbourne have poor health status and engage in behaviours that place their
      health at risk. The high number of respiratory and gastro-intestinal complaints,
      the high level of cigarette smoking and injecting drug use (IDU) and the
      proportion likely to be infected with Mycobacterium tuberculosis (MTb) are all
      issues with important health consequences. Participants recruited from the street
      had significantly poorer health and engaged in more risk behaviours than those
      from accommodation sites; those from the accommodated sample were more likely to
      be infected with Mtb.

PMID- 9659775
TI  - Who can provide antenatal care? The views of obstetricians and midwives.
AB  - OBJECTIVE: To describe the types of antenatal services in NSW maternity hospitals
      and examine the views of midwives and obstetricians about who can provide
      adequate routine antenatal care. MEASUREMENTS: A mail-out questionnaire to
      nursing unit managers (NUMs) explored the types of antenatal services available
      in their hospitals. The questionnaire for 196 midwives and 114 obstetricians
      asked whether they believed six provider/service types could provide adequate
      antenatal care either alone or in conjunction with an obstetrician. FINDINGS: 80%
      of hospitals had GPs providing antenatal care, 53% had obstetricians and 3% had
      visiting midwives; 33% had a public antenatal clinic, 28% a shared care program
      with GPs and 26% midwives' antenatal clinics. Midwives were more likely than
      obstetricians to rate the following as able to provide adequate care alone:
      hospital antenatal clinic (4.7 times more likely); independent midwife (42.9x);
      and community midwives as an outreach hospital service (17x). Obstetricians were
      8.2x more likely than midwives to rate private obstetricians as being able to
      provide adequate care. Midwives were more likely to perceive that independent
      midwives (24.7x more likely) and community midwives as an outreach hospital
      service (15.3x more likely) were able to provide adequate care either alone or in
      conjunction with an obstetrician. CONCLUSION: Most NSW hospitals have GPs
      providing care, but midwives' clinics and independent midwives are less
      available. While midwives and obstetricians hold similar beliefs about GPs
      providing care, substantial differences emerged about the midwife's role. Such
      disparity in opinion may be central in providing options and consistency in care
      for women.

PMID- 9659776
TI  - Responding to health changes: a case study of dental health conditions and
      systems in Japan and Australia.
AB  - This paper presents an analysis of the main policy and organisational issues
      confronting dental health systems in Japan and Australia. Using the changes in
      the epidemiology of dental disease (the oral disease which still affects much of
      public dental health planning) as evidence of fundamental differences in the
      dental health systems of the two countries, the analysis seeks to illuminate,
      first, the structures and processes in both nations to review and implement
      changes to educational practices and workforce planning and, second, the
      constraints on each nation's capability to respond quickly and appropriately to
      the changing dental health needs. It is argued that Japan's ability to rapidly
      change its oral health outcomes, its dental educational system and its
      traditional workforce structure and service-mix, is more constrained than appears
      to be the case in the Australian dental system. The major barriers to Japan's
      ability to change appear to lie in both its traditional cultural decision-making
      processes and in a series of specific health and educational structures which
      place high reliance on a private educational system for health providers, a
      national insurance system which rewards treatment under a fee-for-service
      reimbursement scheme and the lack of a formal, transparent, infra-structure for
      planning health priorities. Barriers to Australia achieving culturally
      appropriate oral health outcomes for the next century appear more related to
      whether national unity in goal setting and implementation strategies can be
      achieved. The constraints in Australia are related to its federal system and to
      the low priority given to financing public dental services.

PMID- 9659777
TI  - Vietnamese-speaking injecting drug users in Melbourne: the need for harm
      reduction programs.
AB  - While research on aspects of injecting drug use (IDU), including injecting and
      sexual risks for HIV transmission, has been progressing in 'mainstream'
      Australian populations, there has been little among non-English speaking
      background (NESB) communities in Australia, particularly the South-East Asian
      communities, of which the Vietnamese is the largest. This exploratory study
      employed and trained peer workers to recruit and interview IDUs of Vietnamese
      origin in Melbourne on a wide range of subjects related to risks associated with
      their drug using, as an initial assessment of risk-taking behaviours for blood
      borne viruses among Vietnamese-speaking IDUs. A finger-prick blood sample was
      taken where possible to measure antibody status to HIV, HBV and HCV. The profile
      which emerged was not dissimilar to that of their English-speaking counterparts
      prior to the benefit of currently available harm-reduction programs. A relatively
      isolated group whose social world often related only to other Vietnamese-speaking
      drug users, they were engaging in unsafe sex and unsafe injecting and were
      unfamiliar with procedures for cleaning injecting equipment and where they could
      seek out information and services, including needle exchanges. This study has
      identified an urgent need not only to promote currently available information and
      services to this group, but also to provide culturally relevant education and
      other harm-reduction measures needed to prevent transmission of HIV, other BBVs
      and STDs. The study has highlighted the lack of responsiveness of mainstream
      health services to the needs of Vietnamese-speaking IDUs.

PMID- 9659778
TI  - Influence of gender and socio-economic status on dietary patterns and nutrient
      intakes in 18-year-old Australians.
AB  - This study used two-day diet records to examine dietary behaviours in 504
      Australian 18 year-olds in relation to gender, socio-economic status (SES) and
      national dietary guidelines. Fat intake exceeded 30% of energy in about 80% of
      subjects and was greater than 40% in about one-quarter. Saturated fat provided
      more than 10% of dietary energy in more than 90% of participants; less than 1%
      achieved a polyunsaturated to saturated fat ratio of at least one. The major food
      groups contributing to fat intake were convenience foods (32% in men, 28% in
      women) and meat (27% in men, 25% in women). Fibre intake was less than 30 g/day
      in 93% of women and 77% of men. Intakes of calcium, magnesium, potassium, and
      vitamins C and A, as a ratio of energy consumption, were greater in women than
      men, while sodium intake was significantly higher in men. Convenience foods were
      the greatest contributors to sodium intake (27% in men, 22% in women) followed by
      meat, bread, and soups and sauces. Greater consumption of cereals, fruit,
      vegetables and low-fat foods in young women of higher SES was reflected in their
      nutrient profile with higher intake of fibre and vitamin C and lower intake of
      fat. Men ate more cereals, meat and sugary foods and less fruit, vegetables and
      low-fat foods. Only 2.5% of men and 4.1% of women conformed with the health
      promotion message, widely publicised locally, to eat two fruits and five
      vegetables daily. Not eating breakfast was associated with lower calcium intake
      in men and women, and lower iron and fibre in take in women. Achieving
      behavioural changes in young adults must take into account differences in dietary
      behaviour related to gender and SES.

PMID- 9659779
TI  - Food Cent$--implementing and evaluating a nutrition education project focusing on
      value for money.
AB  - The Food Cent$ Project aimed to show low income earners a new way to allocate
      their food budget to obtain value for money and balance their diet. It also
      created an infrastructure for program delivery. Strategies included a recommended
      spending model, resources that addressed barriers to healthy eating, together
      with group activities to enhance knowledge and skills. Community volunteers,
      known as Food Cent$ Advisers, were trained to deliver the project by conducting
      budget and cooking sessions for people in their social networks. In 1992, the
      Food Cent$ Project was piloted in the Great Southern Health Region of Western
      Australia. It successfully reached its target group of low income earners who
      were identified as those holding Health Care Cards. Health Care Cards were held
      by 37% of the 150 trained advisers and 52% of the 373 people who attended the
      budget and cooking sessions. Evaluation results demonstrated positive changes in
      self-reported dietary, cooking and shopping behaviours.

PMID- 9659780
TI  - Hepatitis B vaccination coverage of Vietnamese children in south-western Sydney.
AB  - Vaccination coverage since the selective hepatitis B vaccination of neonates of
      high-risk group program introduced in 1987, was measured in 658 children from 301
      Vietnamese families living in the south-western Sydney. The vaccination rate of
      children born after the introduction of the program was twice that of children
      born before its implementation (OR = 2.00, 95% CI 1.65-2.42). The shorter the
      mother's duration of residency in Australia, the more likely her children were to
      be fully vaccinated (OR = 2.49, 95% CI 2.43-2.62). A catch-up vaccination program
      of older siblings is required to assist the public health strategy to reduce the
      morbidity and mortality from hepatitis B viral infection.

PMID- 9659781
TI  - Changing attitudes and beliefs of staff working in methadone maintenance
      programs.
AB  - Starting in 1989, an attempt was made to change the aim of methadone treatment in
      NSW from abstinence to harm-minimisation. A study was undertaken to measure
      change in attitudes among staff working in public methadone programs in Sydney.
      Using scales developed in a 1989 survey, we found a statistically significant and
      meaningful reduction in support for abstinence-oriented policies had occurred by
      1992. There was no change in staff's support for the punishment of illicit drug
      use or their knowledge of the risks and benefits of methadone maintenance. This
      suggests problems with staff attitudes and, indirectly, the effectiveness of
      public health interventions, can be addressed using educational campaigns.

PMID- 9659782
TI  - Hepatitis C virus infection: impacts on behaviour and lifestyle.
AB  - A cross-sectional study was conducted of persons notified with hepatitis C virus
      (HCV) infection on the NSW North Coast during 1993 and 1994. The personal impact
      of infection was investigated using a self-administered questionnaire. Many cases
      were currently well, however nearly half reported fatigue and other adverse
      physical/mental/social outcomes were noted. Tobacco use by subjects was high.
      People with HCV infection require continued support via appropriate screening,
      referral and treatment services; access to information; and countering community
      discrimination, stereotyping and concern about HCV.

PMID- 9659783
TI  - Opportunistic sampling from early childhood centres: a substitute for random
      sampling to determine lead and iron status of pre-school children?
AB  - This report compares the results from two sampling strategies used to determine
      the prevalence of elevated blood lead concentrations and iron status in 12-36
      month old children in Central Sydney. The two methods were stratified random
      sampling using census collector districts and an opportunistic sampling strategy
      using client registers at Early Childhood Centres (ECCs). The response rates were
      75.3% (n = 718 of whom 198 were aged 12-36 months) and 24.1% (n = 304)
      respectively. The geometric mean blood lead concentrations were 0.40 and 0.34
      mumol/L respectively (p = 0.001). The traditional random sampling prevalence
      survey identified a significantly higher proportion of children with blood lead
      concentrations greater than 0.48 (OR = 0.61, 95% CI 0.40-0.93) and 0.72 mumol/L
      (OR = 0.44, 95% CI 0.21-0.92) compared to the simpler opportunistic survey. The
      median plasma ferritin concentration for both studies was 19 micrograms/L (p =
      0.4). The prevalence of iron depletion, iron deficiency and iron deficiency
      anaemia was not significantly different between the two studies. In conclusion,
      opportunistic sampling through ECCs does not appear to be a substitute for the
      traditional random sampling prevalence surveys of determine the prevalence of
      elevated blood lead concentrations in pre-school children in Central Sydney.
      However, opportunistic sampling through ECCs may be an appropriate method for
      monitoring iron status, in particular iron depletion, in pre-school children in
      Central Sydney.

PMID- 9659784
TI  - A sero-prevalence study for 'wallal-type' virus infection among park workers.

PMID- 9659785
TI  - Appropriate yardsticks for measuring population health.

PMID- 9659786
TI  - Priority setting in health care: burden of disease cannot be jettisoned.

PMID- 9659787
TI  - Dealing with the problem of hepatitis C in prisons.

PMID- 9659788
TI  - Concurrent babesiosis and Lyme disease diagnosed in Ontario.

PMID- 9659789
TI  - An outbreak of Rift Valley Fever, eastern Africa, 1997-1998.

PMID- 9659790
TI  - [Transesophageal echocardiography in the evaluation of malfunction of mechanical
      heart valve prostheses. The trump-card dilemma: play is immediately of wait for
      the last hand?].

PMID- 9659791
TI  - Exercise echocardiography: technique and diagnostic value.
AB  - Exercise echocardiography has experienced a rapid rise in clinical acceptance
      because of its recognized ability to detect coronary artery disease in addition
      to attractive features such as portability, versatility and relatively low cost.
      To achieve and maintain accuracy and diagnostic yield, adequate training of the
      sonographer and the cardiologist is essential.

PMID- 9659792
TI  - [Magnetic resonance spectroscopy: what is its role in cardiography?].

PMID- 9659793
TI  - [Evolution of antihypertensive therapy with calcium antagonists: the new
      molecules].

PMID- 9659794
TI  - Gene therapy for cardiovascular disorders.

PMID- 9659795
TI  - Calcium sensitizers in chronic heart failure: inotropic interventions-reservation
      to preservation.
AB  - Newly developed Ca2+ sensitizers possess different mechanisms of action on
      contractile machinery. Increasing maximal Ca(2+)-activated force in addition to
      enhancing Ca2+ sensitivity (MCI-154, EMD 53998, and EMD 57033) could exert
      pronounced positive inotropy and may provide a mechanoenergetic advantage over
      the classic Ca2+ mobilization in the chronically failing heart. EMD 53998 and EMD
      57033 prolong crossbridge attachment time, resulting in negative lusitropy. In
      contrast, pimobendan, levosimendan, and MCI-154 accelerate left ventricular
      relaxation in heart failure, because Ca2+ sensitizing action of these agents may
      be prominent during the early phases of contraction. Therefore, Ca2+ sensitizers
      can avoid the legacy of problems associated with conventional inotropic
      interventions and may break through "reservation" to "preservation" in the
      treatment of chronic heart failure.

PMID- 9659796
TI  - [Effect of A1 adenosine receptor blockade on postischemic damage to the coronary
      microcirculation].
AB  - Recent studies suggest that A1 adenosine receptor antagonists may prevent
      reperfusion injury in the lung and heart. The pathophysiology of this protective
      effect is unclear; a possible inhibition of superoxide anion release from
      neutrophils, or leukocyte activation and platelet aggregation are reported. We
      tested the hypothesis of a blood-independent cardioprotection following A1
      adenosine receptor antagonism with 1,3 dipropyl,8-cyclopentylxanthine (DPCPX).
      Isolated working rat hearts were submitted to 10 and 20 min global ischemia in
      order to assess functional alterations, necrosis enzyme and purine release in
      coronary effluent, arrhythmias, heart weight, ultrastructural morphometry and
      microvascular permeability by FITC-albumin diffusion technique. DPCPX (100 nM)
      was administered to the perfusion buffer before ischemia. In untreated hearts we
      detected a significant impairment of function, associated with a significant
      enzyme and purine release, myocardial edema and ultrastructural damage. In DPCPX
      treated hearts functional and histological damage was significantly reduced
      compared to controls. Moreover, a significant reduction in postischemic
      endothelial permeability (FITC-albumin diffusion, p < 0.02) and ultrastructural
      damage was observed. Our data suggest that A1 adenosine receptor antagonism with
      DPCPX significantly reduces ischemia-reperfusion damage in isolated, crystalloid
      perfused rat heart by a direct reduction of endothelium damage, fluid diffusion
      within the interstitium and improvement of coronary microcirculation.

PMID- 9659797
TI  - [Spontaneous baroreflex control of heart rate during chronic tandropril therapy].
AB  - Differently from other vasodilators, the antihypertensive effect of ACE
      inhibitors is not accompanied by an increase in resting heart rate which suggests
      a modulatory action of these drugs on arterial baroreflex control of heart rate.
      It is debated whether this modulation involve, an increase in gain (or
      sensitivity) of baroreflex mechanisms controlling heart rate or is due to a
      baroreflex control resetting. In this study we investigated the arterial
      baroreflex control of heart rate both in supine rest and during active standing
      before and after 7 and 30 days of treatment with a new ACE-inhibitor,
      trandolapril (2 mg per os oid) in 15 mild hypertensive patients. Baroreflex
      control of heart rate has been dynamically and non-invasively assessed by
      analysis of the continuous relationship between beat-to-beat spontaneous
      fluctuations in systolic blood pressure and pulse interval. By this method,
      sequences of 3 or more consecutive beats in which systolic blood pressure and
      pulse interval change in the same direction (either increasing or decreasing) are
      identified and a linear regression is applied to each individual sequence. The
      mean individual slope of the systolic blood pressure/pulse interval ratio
      obtained by averaging all slopes computed within a given period, is calculated
      and taken as an estimate of the spontaneous baroreflex sensitivity for that
      period. Trandolapril reduced resting blood pressure significantly (from 147.5 +/-
      3.3/95.3 +/- 1.5 to 129.5 +/- 3.7/83.6 +/- 1.6 and 126.6 +/- 3.9/84.5 +/- 1.7
      mmHg after 7 e 30 days, respectively) without affecting heart rate. The treatment
      did not alter baroreflex sensitivity but resulted in an apparent leftward shift
      of the regression line relating systolic blood pressure to pulse interval along
      the pressure axis, reflecting the lower prevailing level of arterial pressure.
      The increases in heart rate and blood pressure induced by standing in control
      conditions were not significantly modified by trandolapril. Baroreflex
      sensitivity was significantly reduced by standing both in control conditions and,
      to the same extent, during treatment. These results suggest that ACE-inhibition
      does not alter the gain of the integrated baroreflex mechanisms controlling heart
      rate, but results in a baroreflex resetting that may explain the lack of
      tachycardia normally observed during antihypertensive therapy with ACE
      inhibitors.

PMID- 9659798
TI  - [Visualization of native internal mammary arteries and aorto-coronary graft by
      means of high resolution color Doppler ultrasonography].
AB  - The internal mammary artery is routinely used for coronary artery bypass grafting
      because of its optimal long-term patency profile. This vessel can be imaged by
      angiography, but only the proximal tract at the origin from the succlavian artery
      can be imaged by conventional echography. The aim of our study was to visualize
      the intrathoracic course of the native and grafted internal mammary arteries by a
      new ultrasound equipment which allows high-resolution transthoracic color Doppler
      imaging of the chest wall vessels and coronary arteries. We studied 35 patients,
      16 non operated and 19 operated of coronary surgery with the internal mammary
      artery grafted to the left anterior descending coronary artery. We used a
      multifrequency 3.5-7 MHz transducer with a small insonating surface, placed at
      the second-fifth intercostal space at the left and right sternal border, to image
      the native mammary arteries. The grafted mammary artery was detected at the
      fourth-fifth left intercostal space 2-4 cm lateral to the sternal border. The
      native left internal mammary artery was visualized in all 16 non operated
      patients, and the right internal mammary artery in 14/16 (87%). The native left
      internal mammary artery peak flow velocity was 41-160 cm/s (mean 81 +/- 34 cm/s),
      and the mean flow velocity was 28-89 cm/s (mean 45 +/- 17 cm/s). The right
      internal mammary artery peak flow velocity was 35-153 cm/s (mean 82 +/- 36 cm/s),
      and mean flow velocity was 21-82 cm/s (mean 46 +/- 22 cm/s). The grafted left
      internal mammary artery was visualized in 16/19 patients (84%), evaluated at 6
      days to 36 months after surgery. Peak diastolic flow velocity ranged from 24 to
      80 cm/s (mean 48 +/- 17 cm/s), and mean diastolic flow velocity ranged from 13 to
      57 cm/s (mean 33 +/- 11 cm/s). The left anterior descending peak flow velocity
      distal to the anastomosis was 22-62 cm/s (mean 37 +/- 15 cm/s) and mean flow
      velocity was 18-53 cm/s (mean 29 +/- 12 cm/s). We conclude that transthoracic
      color Doppler echocardiography allows to image the native and grafted mammary
      arteries, with potential clinical applications in the management of patients with
      coronary artery disease.

PMID- 9659799
TI  - [Dispersion of ventricular recovery time following surgery for tetralogy of
      Fallot: correlation with negative prognostic factors].
AB  - Malignant ventricular arrhythmias have been reported in patients with repaired
      tetralogy of Fallot. The aim of this study was to examine ventricular
      repolarization time indexes, in terms of both absolute measures and dispersion
      across the myocardium, in young patients operated on for tetralogy of Fallot (32
      patients; 19 males and 13 females, mean age 11.1 +/- 3.4 years); these
      electrocardiographic parameters have been shown to be effective in the
      identification of electrical myocardial instability and hence of risk for
      ventricular arrhythmias too. The electrocardiographic data of the study group
      were compared with those of 22 age-matched asymptomatic control subjects (14
      males and 8 females, mean age 12 +/- 1.5 years). Furthermore it has also been
      investigated the possible influence on ventricular repolarization of known
      negative prognostic factors relative to the surgical approach, age at
      intervention, and presence of pulmonary obstruction and/or regurgitation. No
      patients in the study group revealed at the Holter recordings and/or at the
      exercise test severe ventricular arrhythmias. From the analysis of ventricular
      depolarization, expressed by QRS duration, emerged that it resulted significantly
      longer in total Fallot group (p < 0.0001), and in each subgroup (p < 0.05)
      compared to the control group. Particularly, patients operated through a right
      ventricular approach showed higher values of QRS interval (p < 0.05) than those
      operated through combined transatrial-transpulmonary approach. All patients
      operated on for tetralogy of Fallot showed, compared to control subjects, a non
      homogeneous prolongation of ventricular repolarization across the myocardium, as
      confirmed by the significant increase in the absolute indexes of ventricular
      repolarization, JTc (p < 0.001), QT (p < 0.0001) and QTc (p < 0.0001) with a
      concomitant prolongation of the indexes of dispersion of ventricular recovery
      time, QTc dispersion (p < 0.0001), JTc dispersion (p < 0.0001), "adjusted" QTc
      dispersion (p < 0.05) and T peak-T end interval (p < 0.0001). The non homogeneous
      ventricular repolarization across the myocardium, preceding the development of
      arrhythmic events, could be the effect of the right ventricular morphological and
      functional changes of tetralogy of Fallot predisposing to the development of
      ventricular reentry tachyarrhythmias.

PMID- 9659800
TI  - [Personal, familial and environmental factors influencing the inclination of
      smoking in adolescents: differences between sexes and between city and small-town
      dwellers].
AB  - Smoking is a major health hazard. Most cigarette smokers start by the age of 18
      years. The purpose of this study was to assess the prevalence of the intention to
      smoke among the students of a metropolitan compared to a non-metropolitan high
      school. The influence of age, sex, demographic and socio-economic variables, and
      the role of smoking models of family members and friends, were examined. Nine
      hundred forty-five students (529 males and 416 females; mean age 15.8 +/- 1.5
      years) attending a high school in Naples and 442 students (223 males and 219
      females; mean age 16.1 +/- 1.6 years) in Capua, a small town 40 Km distant from
      Naples, filled in an extensive questionnaire on smoking. The prevalence of
      intention to smoke was 10.4% in Naples and 9.3% in Capua. It was related to age
      (p < 0.01) in Naples, but not in Capua. The prevalence of smokers was 24.2% in
      Naples (males 21.6%, females 27.6%; p = 0.038) and 24.1% in Capua (males 29.2%,
      females 19%; p = 0.017). As expected, in both cities intention to smoke was
      associated (p < 0.001) with the strength of existing smoking habit. Students
      smoking over 21 cigarettes/week were more likely to continue than students
      smoking less 21 cigarettes/week, both in Naples and in Capua. More than half of
      smoking students, in both cities, were irresolute about their habit in the
      subsequent year. In Naples, intention to smoke of male students was associated
      with mother's (p = 0.02) and siblings' (p < 0.0001) smoking habit; in female
      students intention to smoke was associated with father's (p = 0.02), mother's (p
      < 0.001), parents' (p < 0.01) and siblings' smoking habit (p = 0.0002). In Capua
      an association was evident, in male students, between intention to smoke and
      paternal smoking habit (p = 0.04); in female students, intention to smoke was
      associated with siblings' smoking habit (p = 0.03). In Naples and in Capua, for
      both sexes, intention to smoke was related to smoking habits of the best friend
      of the same sex (p < 0.0005), the best friend of the opposite sex (p < 0.00005)
      and friends (p < 0.00001). Multivariate analysis showed, in Naples, an
      independent relation between adolescent intention to smoke and age (p = 0.01),
      smoking status of student (p < 0.0001) and friends' smoking habit (p = 0.01). In
      male students intention to smoke was associated with age (p = 0.003), smoking
      habit of student (p < 0.0001), mother's (p = 0.02) and friends' (p = 0.02),
      whereas in females it was associated with smoking behavior of student (p <
      0.0001). In Capua student intention to smoke was related to the smoking status of
      the student (p < 0.0001) and of the best friend of the opposite sex (p < 0.04);
      in male as in female students, intention to smoke was associated with smoking
      habit of the student (p < 0.0001). In conclusion, prevalence of adolescents'
      intention to smoke is similar in two distinct populations of high school students
      of a city and a small town. Smoking is at higher prevalence among females in the
      city and among males in the small town. Intention to smoke increases with age, in
      the great city, and is related to student's existing habit and peer models. More
      than half of smoking students, in both cities, were irresolute about their habit
      in the subsequent year. This study has identified some variables associated with
      adolescents' intention to smoke; we feel that these findings may contribute to a
      better understanding of smoking behavior among adolescents and may have
      preventive implications.

PMID- 9659801
TI  - [Periodic breathing during physical exercise: expression of a form of ventricular
      interdependence?].
AB  - Periodic breathing may be observed in patients with severe congestive heart
      failure during exercise. We describe a patient with such a breathing pattern. We
      noted that nadir of oxygen consumption cycles slightly preceded the nadir of
      ventilation cycles, suggesting that this breathing pattern is due to cardiac
      output periodic changes, possibly through an interplay among the two ventricles
      and the pulmonary blood reservoir.

PMID- 9659802
TI  - [The ophthalmologist].

PMID- 9659803
TI  - Science, options and informed consent.

PMID- 9659804
TI  - CDSPI: run by dentists, for dentists.

PMID- 9659805
TI  - Dentistry after the fee guide.

PMID- 9659806
TI  - Dentistry after the fee guide.

PMID- 9659807
TI  - Dentistry after the fee guide.

PMID- 9659808
TI  - Guidelines on the use of space maintainers--author's reply.

PMID- 9659809
TI  - Guidelines for antibiotic prophylaxis.

PMID- 9659810
TI  - Giving time to your profession can make a difference.

PMID- 9659811
TI  - Central mucoepidermoid carcinoma.
AB  - A case of central mucoepidermoid carcinoma of the mandible is presented along
      with a review of the literature. The histogenesis of this tumor and the
      histologic similarity of the predominantly cystic low-grade central
      mucoepidermoid carcinoma to the glandular odontogenic cyst are discussed.

PMID- 9659812
TI  - The continuing epidemic of HIV and AIDS in 1998.

PMID- 9659813
TI  - A review of common dental treatments during pregnancy: implications for patients
      and dental personnel.
AB  - In general, pregnant females tend to over estimate the risk of teratogenicity in
      the foetus resulting from medical and dental procedures and/or drugs. This may
      cause them to avoid necessary treatment, leading to detrimental health effects
      for both the foetus and themselves. In this review, the concerns of pregnant
      dental patients and personnel will be discussed, including the perceived risks
      associated with amalgam restorations, radiation, local anesthetics, nitrous oxide
      gas, antibiotics and analgesics administered in a dental setting. Pregnant dental
      personnel have special concerns related to their daily occupational exposure to
      mercury and nitrous oxide. After assessing the potential risks of undergoing
      dental treatment during pregnancy, it can be stated that necessary treatment
      should not be with-held. In addition, dental treatments are best performed in the
      second trimester for the benefit of the foetus, and optimal comfort for the
      pregnant woman.

PMID- 9659814
TI  - Dental education in Canada--what lies ahead?

PMID- 9659815
TI  - The myocardial sodium-hydrogen exchanger (NHE) and its role in mediating ischemic
      and reperfusion injury.
AB  - A major mechanism by which the heart adapts to intracellular acidosis during
      ischemia and recovers from the acidosis after reperfusion is through the sodium
      hydrogen exchanger (NHE). There are at least 5 NHE isoforms thus-far identified
      with the NHE-1 subtype representing the major one found in the mammalian
      myocardium. This 110 kDa glycoprotein extrudes protons concomitantly with Na
      influx in a 1:1 stoichiometric relationship rendering the process electroneutral.
      Although NHE is critical for the maintenance of intracellular pH during acid
      loading conditions such as ischemia, there is convincing evidence that it also
      plays a pivotal role in mediating tissue injury during ischemia and reperfusion.
      The mechanism for this paradoxical deleterious role of NHE reflects the fact that
      under conditions of tissue stress, including ischemia, Na-K adenosine
      triphosphate (ATP)ase is inhibited thereby limiting Na extrusion resulting in an
      elevation in intracellular Na concentrations. The latter effect, in turn, will
      increase intracellular Ca concentrations via Na-Ca exchange. In addition, NHE-1
      expression in the diseased myocardium is increased suggesting that elevated
      production of the antiporter represents a long-term adaptive process in an
      attempt by the cardiac cell to regulate intracellular pH which, paradoxically,
      contributes to cardiac pathology. Extensive studies using NHE inhibitors such as
      amiloride or its analogs, or more specific compounds including 3-methylsulphonyl
      4-piperidinoloenzoyl-guanidine methanesulphonate (HOE 694) or 4-isopropyl-3
      methylsulphonylbenzcyl-guanidine methane sulphonate (HOE 642) have consistently
      shown protective effects against ischemic and reperfusion injury in a large
      variety of experimental models and animal species particularly in terms of
      attenuating contractile dysfunction. Such studies have contributed greatly to the
      overwhelming evidence that NHE activation mediates ischemic and reperfusion
      injury. Indeed, HOE 642 (Cariporide) is currently undergoing clinical evaluation
      in high risk cardiac patients. Moreover, there is now emerging evidence that NHE
      may be involved in mediating cardiotoxicity directly produced by various ischemic
      metabolites such as lipid amphiphiles or reactive oxygen species. In this regard,
      we have demonstrated that NHE inhibitors can effectively attenuate the cardiac
      injury produced by lysophosphatidylcholine and hydrogen peroxide. In addition, it
      now appears that NHE inhibition reduces apoptosis in the ischemic myocardium, a
      process which may be of importance in the subsequent development of
      postinfarction heart failure. In conclusion, NHE represents an important adaptive
      process in response to intracellular acidosis resulting in a paradoxical
      contribution to cardiac tissue injury.

PMID- 9659816
TI  - HMGI family proteins: architectural transcription factors in mammalian
      development and cancer.
AB  - The HMGI proteins, a subfamily of the high mobility group (HMG) proteins, play an
      important role in the regulation of gene expression. They bind to AT-rich DNA
      sequences and alter DNA conformation to modulate the binding affinity of
      transcription factors to their cognate sites. They are expressed almost
      exclusively during embryogenesis and Hmgi-c null mice have the mouse pygmy
      phenotype. Studies have revealed the disruption of HMGI family genes in a variety
      of mesenchymal-derived benign tumors. Therefore, the HMGI genes function in the
      coordination of cell proliferation and differentiation during mammalian
      development.

PMID- 9659817
TI  - Vector autoregressive modeling analysis of frequently sampled oral glucose
      tolerance test results. 2. Insulin resistance and secretion after gastrectomy.
AB  - Using the method of vector autoregressive modeling (VAR) analysis of frequently
      sampled oral glucose tolerance test (OGTT) results, we evaluated abnormalities in
      the feedback relationships between plasma glucose and insulin in gastrectomized
      patients to assess insulin secretion capacity and insulin resistance following
      gastrectomy. VAR modeling analysis was applied to the plasma glucose and insulin
      level data from the frequently-sampled 75g-OGTT results of 38 subjects who had
      undergone total or subtotal gastrectomy and 977 controls without gastrectomy.
      After gastrectomy, the predicted response of insulin to a glucose challenge was
      excessive in normal subjects and those with slightly impaired glucose tolerance.
      Furthermore, the glucose response to insulin was clearly positive in
      gastrectomized subjects with moderately to severely impaired glucose tolerance,
      i.e., diabetics, indicating strong insulin resistance. The insulin resistance in
      this situation cannot be explained by decreased peripheral glucose disposal. Our
      results suggest that the lowered glucose tolerance which follows gastrectomy
      results from disturbance of the hormonal relationship between pancreas and
      intestine (entero-insular axis), which causes increased intestinal glucose
      absorption, and the insulin resistance which occurs in response to
      hyperinsulinemia in patients with normal fasting plasma glucose. Disturbance of
      the entero-insular axis may cause not only increased glucose absorption but also
      hyperglucagonemia, both of which contribute to hyperglycemia in diabetic patients
      after gastrectomy.

PMID- 9659818
TI  - Spontaneity in dementia: an analysis of 696 institutionalized elderly patients.
AB  - Activities of daily living (ADL), mental function, spontaneity, emotion and
      problematic behaviors were compared in elderly patients with hip fracture,
      hemiplegia, hemiparesis, senile dementia of Alzheimer type and multi-infarct
      dementia. Osteoarthropathy patients with normal intelligence served as a control
      group. ADL was most strongly affected by spontaneity, then, by intelligence. The
      contributions of emotion and problematic behaviors were not very marked.

PMID- 9659819
TI  - In vivo fluorometric measurement of cerebral oxidative stress using 2'-7'
      dichlorofluorescein (DCF).
AB  - The time course of oxidative stress following cerebral ischemia and reperfusion
      has been obscure, although oxygen-derived free radicals have been postulated to
      play an important role in the progression of reperfusion injury. We have examined
      the time profile of hydrogen peroxide (H2O2) generation in the rat cortex
      following incomplete forebrain ischemia and reperfusion. We used 20 male Sprague
      Dawley rats anesthetized with alpha-chloralose and urethane. A closed cranial
      window was created in the temporoparietal skull, and 2'-7'-dichlorofluorescein
      (DCF), a sensitive fluorescent probe for H2O2, was loaded intracellularly by the
      superfusion technique. We simultaneously monitored DCF fluorescence and
      reflectance from the cortex with an in vivo fluoromicroscope having two
      photomultiplier tubes, and subtracted the hemodynamic artifact from DCF
      fluorescence. Incomplete forebrain ischemia was induced by temporal ligation of
      both common carotid arteries combined with hypotension. The results showed that
      corrected DCF fluorescence remained unchanged during ischemia, but increased
      following reperfusion, indicating enhanced H2O2 generation. Pretreatment by
      intraperitoneal injection of catalase attenuated H2O2 generation significantly.
      that H2O2 generation is mainly enhanced following reperfusion.

PMID- 9659820
TI  - The 6th joint national committee report (JNC-6): new guidelines for hypertension
      therapy from the USA.
AB  - This manuscript will highlight the major elements of the recently published sixth
      Joint National Committee (JNC-6) report. First, a 3-tiered classification of
      overall cardiovascular risk is provided as a guide to the institution of therapy
      with either lifestyle modifications or antihypertensive drugs. Second, the need
      for prevention is stressed. Third, guidelines for the effective use of
      appropriate lifestyle modifications are provided. Fourth, a 3-pronged pathway for
      the choice of critical therapy is provided: one for uncomplicated hypertensive;
      another for those with "compelling" indications for specific drugs, including the
      presence of diabetic nephropathy, congestive heart failure, post-myocardial
      infarction or systolic hypertension in the elderly; the third for those with
      concomitant conditions that may be either favorably or unfavorably affected by
      specific types of drugs. In addition, the report emphasizes the need to achieve
      the goal of less than 140/90 mmHg by a progressive process of therapy and, if
      necessary, referral to a hypertension specialist. Recommendations are made for
      improved adherence to therapy, therapy of resistant hypertension and hypertensive
      crises.

PMID- 9659821
TI  - A female with a rapidly growing tumor in the right hypochondriac region and
      severe anemia.

PMID- 9659822
TI  - Student opinions on managed care.

PMID- 9659823
TI  - Patient satisfaction: can patients evaluate the quality of health care?

PMID- 9659824
TI  - Routine procedure--bad outcome.

PMID- 9659825
TI  - Primary non-Hodgkin's lymphoma of the breast.

PMID- 9659826
TI  - Arrhythmia mechanism of unexpected sudden death following lateral medullary
      infarction.

PMID- 9659827
TI  - Drug-resistant tuberculosis of the brain in a two-year-old child.

PMID- 9659828
TI  - The economic impact of national health service corps physicians on rural
      communities.

PMID- 9659829
TI  - A man with rapidly progressive pulmonary infiltrates and hypoxia.

PMID- 9659830
TI  - [Medication errors--the top of an iceberg?].

PMID- 9659831
TI  - [Hypercalcemia--diagnosis and treatment].

PMID- 9659832
TI  - [Did pneumococcal endocarditis come back?].
AB  - Endocarditis caused by pneumococci represents 1-5% of all cases of endocarditis
      according to publications from different western countries. Necropsy studies show
      frequencies of up to 14% of all cases of endocarditis. It usually occurs as a
      complication to a pneumococcal pneumonia but other foci might be seen.
      Concomitant meningitis is seen in 20-85% of patients suffering from pneumococcal
      endocarditis. By knowing this disease entity there is a good possibility for
      treatment with antibiotics and valve replacement, but if overlooked the mortality
      is high. The frequency of pneumococcal endocarditis might be underestimated.
      Careful stethoscopic examination for heart murmurs should be a part of the
      clinical examination in case of invasive pneumococcal disease, especially with
      concomitant meningitis. Since bacteriaemia due to pneumococci is diagnosed with
      increasing frequency in many Northern European countries, special attention
      should be paid to pneumococcal endocarditis. The literature is reviewed with
      reference to pathology, pathogenesis, frequency, clinical presentation,
      diagnosis, treatment and prognosis.

PMID- 9659833
TI  - [Evaluation of functional importance of coronary artery stenosis by intracoronary
      Doppler blood flow velocity measurement].
AB  - Intracoronary doppler blood flow velocity measurements supply important
      information for clinical decision making during angioplasty, especially with
      regard to stenoses of ambiguous severity. In the presence of an intermediate
      stenosis of unknown physiological impact (40-60%), determination of normal flow
      parameters (coronary flow reserve: CFR, diastolic to systolic velocity ratio:
      DSVR and proximal to distal velocity ratio: P/D) will make deferment of treatment
      acceptable. Post-angioplasty success can be based on restoral of normal
      flowparameters. The inability to achieve normal CFR immediately after angioplasty
      does not indicate an unsuccessful procedure, it remains to be shown whether a
      lack of normalization of DSVR and/or P/D does so. Continuous post-lesional flow
      monitoring can show and quantify the existence of collateral flow.

PMID- 9659834
TI  - [Discrepancies between medical records and dispensing records in two large
      hospital departments in Copenhagen].
AB  - This study was performed to investigate the possible differences between
      prescribed medicine, as entered in the hospital record, and the medicine
      dispensed to the patients according to the nurse's dispensing records (NDR's) in
      two clinical departments at a Copenhagen University Hospital. Discrepancies were
      defined as either dosage differences or drugs only present in one file, and were
      divided into major and minor discrepancies, according to clinical significance.
      In the first department, discrepancies were found in 61.4% of the records, and
      major discrepancies were found in 35.1%. In the second department, discrepancies
      were found in 70.5% of the cases, and major discrepancies in 42.5%. No
      correlation was found between the number of drugs per patient and the number of
      discrepancies. A significant difference exists between what is prescribed, and
      what is dispensed. This can have clinical as well as legal consequences.

PMID- 9659835
TI  - [Written documentation of drug prescriptions. Accordance between medical records
      and dispensing records].
AB  - A comparison of drug prescriptions entered on case records and nurses' drug lists
      is presented. Of 144 patients admitted to a general internal medicine ward, nine
      received no drugs. The remaining 135 had 606 (75.0%) items on both case record
      and drug list, 114 (14.1%) on the case record only, and 88 (10.9%) on the drug
      list only. For 48 patients (35.6%) drug lists were in accordance with their case
      record concerning the number and type of drug prescribed. Prescriptions on both
      documents were characterised by lack of accuracy. Of the 709 prescriptions on
      case records and 684 on drug lists, 428 (60.4%) and 411 (60.1%) respectively were
      unambiguous. CONCLUSION: Drug prescribing based on transcription from case
      records to nurses' drug lists implies a considerable risk of discrepancies. Thus,
      there is a significant risk of incorrect drug administration. A standardised card
      for drug prescriptions for common use by both physicians and nurses will
      therefore now be taken into use.

PMID- 9659836
TI  - [Self-rated health as a predictor of ischemic heart disease development].
AB  - The study objective was to analyse the association between self-rated health and
      the incidence of fatal and non-fatal coronary heart disease in a Danish cohort
      followed up over 16 years. The study included 1052 men and women born in 1936.
      During the 16 years' follow-up 50 cases of coronary heart disease were registered
      either with the Danish register of deaths or the register of hospital admissions.
      Univariate analysis showed the following relative risks of coronary heart disease
      in the four self-rated health groups: "extremely good": 1.0, "good": 4.0, "poor":
      5.8, "miserable": 12.1 (p = 0.02). After control for the conventional coronary
      risk factors and a substantial number of other potential confounders the relative
      risks were: 1.0, 4.2, 6.5, and 18.6 (p = 0.02) respectively. Self-rated health
      was an independent predictor of coronary heart disease in this recent cohort. If
      confirmed, the association between self-rated health and coronary heart disease
      may lead to new insights into psychosocial processes leading to this disease.

PMID- 9659837
TI  - [Frequent mutation doubles the risk of ischemic heart disease in women].
AB  - Lipoprotein lipase degrades triglycerides in plasma and as a by-product produces
      HDL particles. Genetic variation in lipoprotein lipase may therefore affect
      cardiovascular risk. We tested 9214 men and women from a general population
      sample and 948 patients with ischaemic heart disease for the Asn291Ser
      substitution in lipoprotein lipase. The allele frequency in the general
      population was 0.024 and 0.026 for women and men, respectively. In comparison
      with non-carriers, female heterozygous probands had increased plasma
      triglycerides (delta = 0.23 mmol/L), while HDL cholesterol was reduced in both
      female and male carriers (delta = 0.18 mmol/L and delta = 0.11 mmol/L,
      respectively). A similar phenotype was found in six homozygous carriers. On
      multiple logistic regression analysis, plasma triglycerides and HDL cholesterol
      were independent predictors of ischaemic heart disease in both genders. On
      univariate analysis, odds ratios for ischaemic heart disease in probands were
      1.89 in women (95% confidence interval: 1.19-3.01) and 0.90 (0.62-1.31) in men,
      and on multivariate analysis 1.98 (1.11-3.53) in women and 1.02 (0.65-1.60) in
      men. This study demonstrates that a single common mutation in the lipoprotein
      lipase gene is associated with elevated plasma triglycerides and reduced HDL
      cholesterol levels, whereby carriers, in particular women, seem to be predisposed
      to ischaemic heart disease. It cannot be excluded, however, that male carriers of
      this substitution may represent a subset of low-HDL individuals without raised
      triglycerides, not predisposed to ischaemic heart disease.

PMID- 9659838
TI  - [Is Letigen contraindicated in hypertension? A double-blind, placebo controlled
      multipractice study of Letigen administered to normotensive and adequately
      treated patients with hypersensitivity].
AB  - The aim of this study was to study how the slimming drug, Letigen, containing
      ephedrine (E) 20 mg and caffeine (C) 200 mg (E + C) affects blood pressure in
      normotensive and hypertensive patients treated with adrenergic beta-receptor
      blocking drugs and/or other antihypertensive agents, during a period of six
      weeks. We followed 136 patients in a double blind, randomised, placebo controlled
      study of five parallel groups of overweight patients from general practices. The
      systolic blood pressure was reduced significantly (5.5 mmHg) in the patients
      treated with antihypertensive agents other than betablockers, plus E + C. In
      normotensive patients treated with E + C the systolic and diastolic blood
      pressure declined significantly (4.4/3.9 mmHg). A mean loss of weight of 4 kg
      over six weeks was significant for all groups. This study does not support the
      assumption that E + C should cause rises in blood pressure in either normotensive
      or hypertensive obese patients. The antihypertensive effect of the betablockers
      was not reversed by E + C.

PMID- 9659839
TI  - [Pneumococcal endocarditis].
AB  - With the increasing frequency of pneumococcal bacteriaemia in Denmark during the
      last ten years, it is important to be aware of pneumococcal endocarditis. Two
      cases of pneumococcal endocarditis are described and an estimate is made of the
      incidence. The first case had endocarditis of the aortic valve with concomitant
      meningitis. Acute valve replacement was necessary and recovery was complete. The
      second case, which started with an embolic episode, also had endocarditis of the
      aortic valve. This patient recovered after treatment with antibiotics.

PMID- 9659840
TI  - [Gastric carcinoid tumor in pernicious anemia].
AB  - A case of a 39 year-old woman with recently diagnosed PA and a GCT is reported.
      Recent surveys have shown that GCTs occur far more frequently in patients with
      chronic atrophic gastritis type A (+/- PA) than previously noted. This may be due
      to an improved endoscopic technique and the use of specific immunostains, such as
      chromogranin A, which in our case was essential in avoiding the diagnostic
      pitfall of an adenocarcinoma. The pathogenesis and the management of type-1 GCT
      are discussed.

PMID- 9659841
TI  - [Air travel and deep venous thrombosis].
AB  - A case of deep venous thrombosis (DVT) in a woman with polio sequelae is
      reported. The patient presented with classical sign of DVT, probably caused by
      air travel. Guidelines for air travellers in order to prevent the economy class
      syndrome are presented.

PMID- 9659842
TI  - [The vessel of the Danaides].

PMID- 9659843
TI  - [Picture of the month. Schistosomiasis haematobia].

PMID- 9659844
TI  - [Cow's milk-based infant formula to newborns of parents with insulin-dedent
      diabetes].

PMID- 9659845
TI  - [Local analgesia in inguinal hernia surgery: progress or retrogression?].

PMID- 9659846
TI  - Treatment for major depression in managed care and fee-for-service systems.

PMID- 9659847
TI  - Images in neuroscience. Brain development, IV. Axon routing and rerouting.

PMID- 9659848
TI  - What happens to "bad" girls? A review of the adult outcomes of antisocial
      adolescent girls.
AB  - OBJECTIVE: The purpose of this article is to review critically the data on the
      adult outcomes of adolescent girls with antisocial behavior. METHOD: Five
      literature databases were searched for studies on the adult outcomes of girls
      with either conduct disorder or delinquency. RESULTS: Twenty studies met the
      inclusion criteria. As adults, antisocial girls manifested increased mortality
      rates, a 10- to 40-fold increase in the rate of criminality, substantial rates of
      psychiatric morbidity, dysfunctional and often violent relationships, and high
      rates of multiple service utilization. Possible explanations for these findings
      include a pervasive biological or psychological deficit or baseline heterogeneity
      in the population of antisocial girls. CONCLUSIONS: This review establishes that
      female adolescent antisocial behavior has important long-term individual and
      societal consequences. At present, there are insufficient data to enable us to
      prevent these outcomes or treat them if they occur. Future research should
      include cross-sectional studies detailing the phenomenology of female antisocial
      behavior and longitudinal investigations that not only track development into
      adulthood but also explore the role of potential modifying variables such as
      prefrontal lobe dysfunction and psychiatric comorbidity.

PMID- 9659849
TI  - Use of health services by hospitalized medically ill depressed elderly patients.
AB  - OBJECTIVE: The authors examined whether depression is associated with greater use
      of health services by elderly medical patients before and during hospitalization.
      METHOD: Depression and recent use of health services were assessed in 542
      patients aged 60 or over who were consecutively admitted to university medical
      services. Depression was measured by using the Center for Epidemiologic Studies
      Depression Scale, the Hamilton Depression Rating Scale, and the depressive
      disorders section of the National Institute of Mental Health Diagnostic Interview
      Schedule, which was administered by a psychiatrist. RESULTS: After age, sex,
      race, education, and severity of medical illness were controlled for, Hamilton
      depression score significantly predicted hospital days in the past year, hospital
      days and total inpatient days (hospital plus nursing home) in the past 3 months,
      and number of outpatient medical visits in the past 3 months. Depressed patients
      had more hospital days in the past year and had more hospital days, total
      inpatient days, and outpatient medical visits in the past 3 months than did
      nondepressed patients. Associations between depression and length of index
      hospital stay, home health visits, nursing home days, and number of prescription
      medications disappeared when severity of medical illness was controlled. Mental
      health visits were no more common among depressed than nondepressed patients.
      CONCLUSIONS: Depressed elderly medical inpatients used more hospital and
      outpatient medical services than nondepressed patients, but they did not receive
      more mental health services. Efforts by primary care physicians and third-party
      payers to identify and treat depression in this population are needed.

PMID- 9659850
TI  - Physical health, depressive symptoms, and managed care enrollment.
AB  - OBJECTIVE: This study used a national employee survey to test the hypothesis that
      symptomatic individuals in general, and individuals with depressive symptoms in
      particular, are disproportionately enrolled in fee-for-service health care plans
      as compared to health maintenance organizations (HMOs). METHOD: The study
      analyzed data from the 1993 Employee Health Care Value Survey, a questionnaire
      distributed to employees of three large corporations. The sample comprised 20,283
      employees covering six U.S. geographic regions and 46 health plans. The authors
      used logistic regression to model the association between HMO enrollment and
      presence of physical and depressive symptoms, measured by subscales derived from
      the Medical Outcomes Study 36-item Short-Form Health Survey, adjusting for
      health, demographic, and insurance variables. RESULTS: In unadjusted models,
      enrollees in fee-for-service plans had higher rates of both depressive and
      physical symptoms than HMO enrollees. After adjustment for age alone or for age
      and other potential confounders, there was no difference in physical symptoms
      between plan types. However, individuals with high levels of depressive symptoms
      were 16% less likely to be enrolled in HMOs than in fee-for-service plans after
      adjustment for age, other demographic variables, physical health status, and
      insurance characteristics. CONCLUSIONS: This study provides evidence that
      symptomatic individuals are more likely to be enrolled in fee-for-service plans
      than in HMOs. While much of the effect for physical symptoms may be explained by
      differences in demographic variables, particularly age, the difference in
      depressive symptoms appears to be independent of those variables.

PMID- 9659851
TI  - Expenditures for the treatment of major depression.
AB  - OBJECTIVE: Health policy makers lack accurate information about per capita
      spending for the treatment of major depression, the distribution of those
      expenditures, and the proportion of the health care dollar consumed by depression
      treatment. METHOD: The authors recruited and followed a community cohort of
      individuals with major depression; the 298 subjects were either enrolled in fee
      for-service insurance plans or self-insured. Charges for all health care services
      received during the year following baseline were abstracted from medical and
      insurance records. RESULTS: Over the course of 1 year, 48.1% of the subjects
      received depression treatment. The per capita total expenditure for inpatient and
      outpatient depression treatment averaged $631, with a median of $152, for the
      treated subjects. Just 4.9% of the treated subjects consumed 45.0% of the
      outpatient expenditures. Depression treatment consumed only 8 cents of every
      health care dollar spent on the patients treated for depression. CONCLUSIONS:
      Studies are needed to examine how the level and distribution of expenditures for
      depression treatment change under managed care and to determine whether and how
      any differences affect outcomes in the afflicted population. Managed care
      attempts to contain costs by limiting outpatient care may not affect total health
      care expenditures dramatically, since depression treatment consumes such a
      minuscule portion of the health care dollar spent on this population.

PMID- 9659852
TI  - Characteristics of psychiatrists who perform ECT.
AB  - OBJECTIVE: Use of ECT is highly variable, and previous study has linked its
      availability to the geographic concentration of psychiatrists. However, less than
      8% of all U.S. psychiatrists provide ECT. The authors analyzed the
      characteristics of psychiatrists who use ECT to understand more fully the
      variation in its use and how changes in the psychiatric workforce may affect its
      availability. METHOD: Data from the 1988-1989 Professional Activities Survey were
      examined to investigate the influence of demographic, training, clinical
      practice, and geographic characteristics on whether psychiatrists use ECT.
      RESULTS: Psychiatrists who provided ECT were more likely to be male, to have
      graduated from a medical school outside the United States, and to have been
      trained in the 1960s or 1980s rather than the 1970s. They were more likely to
      provide medications than psychotherapy, to practice at private rather than state
      and county public hospitals, to treat patients with affective and organic
      disorders, and to practice in a county containing an academic medical center.
      CONCLUSIONS: Demographic and training characteristics significantly influence
      whether a psychiatrist uses ECT. Opposing trends in the U.S. psychiatric
      workforce could affect the availability of the procedure. Expanding training
      opportunities for ECT and making education, training, and testing more consistent
      nationwide could improve clinicians' consensus about ECT and narrow variation in
      its use.

PMID- 9659853
TI  - Lithium discontinuation and subsequent effectiveness.
AB  - OBJECTIVE: Several reports have raised concern that the discontinuation of
      lithium may result in treatment resistance following recurrence of affective
      disorder. This report explores this possibility. METHOD: The data derive from a
      large, naturalistic follow-up of patients with major depressive disorder or
      mania. Twenty-eight of the patients in the study were free of lithium and
      experiencing an episode of mania or schizoaffective mania diagnosed according to
      Research Diagnostic Criteria when they entered the study, recovered while taking
      lithium, later experienced a recurrence while not taking lithium, and then
      resumed lithium treatment. Survival analyses of time to recovery and,
      subsequently, time to recurrence, used continued lithium treatment as an
      additional censoring variable. RESULTS: Patients given lithium recovered no more
      quickly from their index episode than they did from their first prospectively
      observed episode. Moreover, lithium prophylaxis appeared no less effective after
      the first prospectively observed episode than after the index episode.
      CONCLUSIONS: These findings provide no evidence that lithium discontinuation
      results in treatment resistance when lithium is resumed.

PMID- 9659854
TI  - Pilot study on patients' and spouses' attitudes toward potential genetic testing
      for bipolar disorder.
AB  - OBJECTIVE: The purpose of this pilot study was to gain information about
      attitudes of individuals with bipolar disorder and their spouses toward some of
      the ethical and social issues arising from rapidly advancing genetic research on
      bipolar disorder. METHOD: Patients with bipolar disorder and their unaffected
      spouses were asked to answer questionnaires assessing their knowledge and
      attitudes about treatment response rates for bipolar disorder, probability of
      inheritance, genetic testing, disclosure of genetic information, abortion,
      marriage, and child-bearing. RESULTS: The overwhelming majority of the patients
      and spouses said that they would take advantage of genetic tests for bipolar
      disorder if such tests were to become available. Most patients and spouses agreed
      that the benefits of knowing whether one carries a gene for bipolar disorder
      would outweigh the risks. The decisive majority of respondents also felt that
      they would not abort a fetus that carried a gene for bipolar disorder.
      Furthermore, most patients and spouses agreed that the knowledge that one of them
      carried a gene for bipolar disorder would not have deterred them from marriage or
      childbearing. CONCLUSIONS: The results of this study suggest that most
      individuals believe that they would benefit from the use of genetic testing for
      bipolar disorder if it were to become available. Follow-up studies using a
      broader patient sample and nonclinical control groups would be useful in further
      evaluating the issues addressed in this pilot study.

PMID- 9659855
TI  - Decreasing length of stay: are there effects on outcomes of psychiatric
      hospitalization?
AB  - OBJECTIVE: The authors compared hospital outcomes for depressed patients
      hospitalized between 1988 and 1996. METHOD: Between 1988 and 1996, 206 depressed
      patients in three cohorts were evaluated at admission; of these, 161 (78.2%) were
      evaluated at discharge and 119 (78.3% of those followed [N = 152]) 1 month later.
      Evaluation consisted of measures of symptoms, global functioning, self-concept,
      ego defenses, work and social functioning, and readmission. RESULTS: Lengths of
      stay significantly declined over time (26.5 versus 19.5 versus 8.3 days). At
      discharge, the most recently hospitalized group showed higher residual depression
      and lower residual global functioning scores than the other groups. Other
      measures did not differ among the groups at discharge. One month after discharge,
      the shortest-stay group continued to show lower global functioning, as well as
      lower quantity of work functioning. Readmission rates were equal. Within the
      shortest-stay group, no differences in outcome were found between patients
      treated in a partial hospital and those not so treated. CONCLUSIONS: Improvement
      during very brief admission is comparable to that in longer stays on many aspects
      of functioning. However, depressed patients discharged more quickly show
      significantly higher residual levels of depressive symptoms and lower levels of
      global functioning, which may place them at greater risk for adverse outcomes in
      the immediate posthospital period.

PMID- 9659856
TI  - Effects of antidepressant treatment on neuroactive steroids in major depression.
AB  - OBJECTIVE: There is evidence from animal studies that fluoxetine may enhance the
      concentrations of neuroactive steroids. Therefore, the authors investigated
      whether clinically effective treatment with antidepressants may alter the
      concentrations of neuroactive steroids in patients suffering from a major
      depressive episode. METHOD: In the first study, eight drug-naive outpatients with
      major depression were studied during treatment with fluoxetine. In a
      complementary study, 11 inpatients with major depression were studied during a
      severe depressive episode and after recovery following treatment with different
      antidepressants. Plasma samples were quantified for neuroactive steroids by means
      of a highly sensitive and specific combined gas chromatography/mass spectrometry
      analysis. RESULTS: During depression, there was a significant decrease in 3
      alpha, 5 alpha-tetrahydroprogesterone (3 alpha, 5 alpha-THP) and 3 alpha, 5 beta
      THP concentrations, both of which are positive modulators of the gamma
      aminobutyric acidA receptor, and a concomitant increase in 3 beta, 5 alpha-THP
      levels. This dysequilibrium of neuroactive steroids could be corrected by
      treatment with different antidepressants. CONCLUSIONS: These results provide the
      first clinical evidence of a possible role of neuroactive steroids in successful
      antidepressant therapy.

PMID- 9659857
TI  - Olanzapine compared with chlorpromazine in treatment-resistant schizophrenia.
AB  - OBJECTIVE: The purpose of this study was to compare the efficacy of olanzapine
      with that of chlorpromazine plus benztropine in patients with treatment-resistant
      schizophrenia. METHOD: One hundred three previously treatment-resistant patients
      with schizophrenia diagnosed according to the DSM-III-R criteria were given a
      prospective 6-week trial of 10-40 mg/day of haloperidol. Eighty-four of them
      failed to respond to that trial and agreed to be randomly assigned to an 8-week
      fixed-dose trial of either 25 mg/day of olanzapine alone or 1200 mg/day of
      chlorpromazine plus 4 mg/day of benztropine mesylate. RESULTS: Fifty-nine (70%)
      of the 84 subjects completed the trial. The primary outcome measures were Brief
      Psychiatric Rating Scale total score and positive symptom score, Scale for the
      Assessment of Negative Symptoms global score, and Clinical Global Impression
      score. An analysis of variance for the subjects who completed the study showed no
      difference in efficacy between the two drugs. Seven percent of the olanzapine
      treated patients responded according to a priori criteria; no chlorpromazine
      treated patients responded. The olanzapine-treated patients had fewer motor and
      cardiovascular side effects than the chlorpromazine-treated patients.
      Extrapyramidal symptoms and akathisia were similar in the two groups, although no
      antiparkinsonian drugs were used in the olanzapine group. CONCLUSIONS: Olanzapine
      and chlorpromazine showed similar efficacy, and the total amount of improvement
      with either drug was modest. Olanzapine-treated patients had fewer side effects
      than chlorpromazine-treated patients.

PMID- 9659858
TI  - 5-HT2 and D2 receptor occupancy of olanzapine in schizophrenia: a PET
      investigation.
AB  - OBJECTIVE: Olanzapine is a new atypical antipsychotic recently introduced for the
      treatment of schizophrenia. The purpose of this study was to investigate
      olanzapine's binding to the serotonin 5-HT2 and dopamine D2 receptors in
      schizophrenic patients being treated with clinically relevant doses. METHOD:
      Twelve patients with schizophrenia were randomly assigned to 5, 10, 15, or 20
      mg/day of olanzapine in a prospective fashion. Three other subjects taking 30-40
      mg/day were also included. Once steady-state plasma levels were achieved,
      dopamine D2 and serotonin 5-HT2 receptors were assessed by using [11C]raclopride
      and [18F]setoperone positron emission tomography imaging, respectively. Ratings
      of clinical status, extrapyramidal side effects, and prolactin levels were also
      obtained. RESULTS: Olanzapine induced near saturation of the 5-HT2 receptors,
      even at 5 mg/day. Its D2 occupancy increased with dose: patients taking 5-20
      mg/day showed 43%-80% D2 occupancy, while patients taking 30-40 mg/day showed 83%
      88%. CONCLUSIONS: Olanzapine is a potent 5-HT2 blocker and shows a higher 5-HT2
      than D2 occupancy at all doses. However, its D2 occupancy is higher than that of
      clozapine and similar to that of risperidone. In the usual clinical dose range of
      10-20 mg/day, its occupancy varies from 71% to 80%, and this restricted range may
      explain its freedom from extrapyramidal side effects and prolactin elevation.
      However, doses of 30 mg/day and higher are associated with more than 80% D2
      occupancy and may have a higher likelihood of prolactin elevation and
      extrapyramidal side effects.

PMID- 9659860
TI  - Posttraumatic stress disorder following an air disaster: a prospective study.
AB  - OBJECTIVE: The purpose of this study was to determine predictors of posttraumatic
      stress disorder (PTSD) in health care workers exposed to a disaster, in order to
      facilitate early case identification and prevention of subsequent morbidity.
      METHOD: Following an air disaster, 355 military medical health care workers were
      studied over an 18-month follow-up period. Measures included assessment of
      peritraumatic reactions associated with the disaster, the frequency of other
      stressful events after the disaster, and standard PTSD rating scales at 6, 12,
      and 18 months. RESULTS: Multivariate logistic regression of data on health care
      workers who cared for victims of the air disaster showed that PTSD was more
      likely to develop in those who had not completed college, those who had worked
      with burn victims, those who had experienced more stressful life events in a
      period of approximately 6 months following the disaster, and those who
      experienced emotional numbness immediately after the disaster. CONCLUSIONS:
      Results suggest that lower levels of education, exposure to grotesque burn
      injuries, stressful life events following exposure, and feelings of numbness
      following exposure are useful predictors of subsequent development of PTSD.

PMID- 9659859
TI  - Sleep disturbances in the Vietnam generation: findings from a nationally
      representative sample of male Vietnam veterans.
AB  - OBJECTIVE: This study analyzed questionnaire items that address complaints about
      sleep from the National Vietnam Veterans Readjustment Study, a nationally
      representative sample of the 3.1 million men and women who served in Vietnam.
      This study compared the frequency of nightmares and difficulties with sleep onset
      and sleep maintenance in male Vietnam theater veterans with male Vietnam era
      veteran and male civilian comparison subjects. It focused on the role of combat
      exposure, nonsleep posttraumatic stress disorder (PTSD) symptoms, comorbid
      psychiatric and medical disorder, and substance abuse in accounting for different
      domains of sleep disturbance. METHOD: The authors undertook an archival analysis
      of the National Vietnam Veterans Readjustment Study database using correlations
      and linear statistical models. RESULTS: Frequent nightmares were found
      exclusively in subjects diagnosed with current PTSD at the time of the survey
      (15.0%). In the sample of veterans who served in Vietnam (N = 1,167), combat
      exposure was strongly correlated with frequency of nightmares, moderately
      correlated with sleep onset insomnia, and weakly correlated with disrupted sleep
      maintenance. A hierarchical multiple regression analysis showed that in Vietnam
      theater veterans, 57% of the variance in the frequency of nightmares was
      accounted for by war zone exposure and non-sleep-related PTSD symptoms. Alcohol
      abuse, chronic medical illnesses, panic disorder, major depression, and mania did
      not predict the frequency of nightmares after control for nonsleep PTSD symptoms.
      CONCLUSIONS: Frequent nightmares appear to be virtually specific for PTSD. The
      nightmare is the domain of sleep disturbance most related to exposure to war zone
      traumatic stress.

PMID- 9659861
TI  - Outcome of anorexia nervosa: a case-control study.
AB  - OBJECTIVE: Although there have been many studies of the outcome of anorexia
      nervosa, methodological weaknesses limit their interpretation. The authors used a
      case-control design to try to improve knowledge about the outcome of anorexia
      nervosa. METHOD: All new female patients referred to an eating disorders service
      between Jan. 1, 1981, and Dec. 31, 1984, who had probable or definite anorexia
      nervosa were eligible for inclusion. Of these women, 86.4% (N = 70) were located
      and agreed to participate. The comparison group (N = 98) was a random community
      sample. All subjects were interviewed with a structured diagnostic instrument.
      RESULTS: A minority of the patients (10%) continued to meet the criteria for
      anorexia nervosa a mean of 12 years after initial referral. Even among those who
      no longer met these criteria, relatively low body weight and cognitive features
      characteristic of anorexia nervosa (perfectionism and cognitive restraint)
      persisted. The rates of lifetime comorbid major depression, alcohol dependence,
      and a number of anxiety disorders were very high. CONCLUSIONS: In the managed
      care/brief treatment era, therapeutic approaches with an excessive focus on
      weight gain that neglect the detection and treatment of associated psychological
      features and comorbidity may be inappropriate. Anorexia nervosa is a serious
      psychiatric disorder with substantial morbidity.

PMID- 9659862
TI  - Guided self-change for bulimia nervosa incorporating use of a self-care manual.
AB  - OBJECTIVE: The aim of this study was to evaluate the effectiveness of guided self
      change for bulimia nervosa. METHOD: Sixty-two patients with DSM-III-R-defined
      bulimia nervosa were randomly assigned to 1) use of a self-care manual plus eight
      fortnightly sessions of cognitive behavior therapy (guided self-change) or 2) 16
      sessions of weekly cognitive behavior therapy. RESULTS: At the end of treatment
      and at follow-up an average of 43 weeks after the end of therapy, substantial
      improvements had been achieved in both groups on the main outcome measures:
      eating disorder symptoms according to experts' ratings (Eating Disorder
      Examination subscores on overeating, vomiting, dietary restraint, and shape and
      weight concerns), self-reports (Bulimic Investigatory Test Edinburgh), and a 5
      point severity scale. Also, improvement was seen on the subsidiary outcome
      measures: the Beck Depression Inventory, the Self-Concept Questionnaire, and
      knowledge of nutrition, weight, and shape. At follow-up, 71% of the cognitive
      behavior therapy group had not binged or vomited during the week preceding. In
      the guided self-change group, 70% had not binged and 61% had not vomited during
      the week before follow-up. CONCLUSIONS: Guided self-change incorporating use of a
      self-care manual offers an approach that can be as effective as standard
      cognitive behavior therapy in the long term and can considerably reduce the
      amount of therapist contact required.

PMID- 9659863
TI  - Adolescent physical abuse: risk for adolescent psychiatric disorders.
AB  - OBJECTIVE: The present study examined whether physical abuse functions as an
      additional risk factor for adolescent psychopathology after other important known
      risk factors are controlled for. METHOD: The authors recruited 99 adolescents
      aged 12 to 18 years directly from the New York State Department of Social
      Services after official documentation of physical abuse. The abused adolescents
      were compared to 99 nonabused adolescents matched for age, gender, race, and
      community income. Diagnostic interviews and measures of selected risk factors for
      psychopathology were administered to the adolescents and their parents and then
      entered into a multiple logistic regression model testing the added risk
      contributed by physical abuse to adolescent psychopathology. RESULTS: Physical
      abuse added significantly to other risk factors in accounting for lifetime
      diagnoses of major depression, dysthymia, conduct disorder, drug abuse, and
      cigarette smoking. Physical abuse also contributed significantly to prediction of
      current adolescent unipolar depressive disorders, disruptive disorders, and
      cigarette smoking. CONCLUSIONS: Since physically abused adolescents are at
      greater risk for the development of psychiatric disorders, recognition of
      adolescent abuse and the provision of psychiatric and substance abuse services
      may reduce morbidity.

PMID- 9659864
TI  - Family history and psychiatric comorbidity in persons with compulsive buying:
      preliminary findings.
AB  - OBJECTIVE: The authors explored the family history and psychiatric comorbidity of
      a group of compulsive buyers who volunteered for medication studies. Compulsive
      buying is characterized by inappropriate shopping and spending behavior that
      leads to impairment. METHOD: Thirty-three subjects who met the criteria of
      McElroy and colleagues for compulsive buying, and who scored more than two
      standard deviations above the mean on the Compulsive Buying Scale, were
      recruited. Twenty-two comparison subjects were recruited in the course of another
      study, and the presence of obsessive-compulsive disorder was the only reason for
      exclusion. Both groups were administered the Structured Clinical Interview for
      DSM-III-R disorders. The Family History Research Diagnostic Criteria were used to
      collect information about psychiatric disorders in first-degree relatives.
      RESULTS: Compulsive buyers had a mean age of 40 years; two (6%) were men.
      Comparison subjects had a mean age of 39 years; six (27%) were men. The two
      groups differed in gender distribution but not in age, marital status, or
      educational achievement. Compulsive buyers were more likely than comparison
      subjects to have lifetime mood disorders (especially major depression) and to
      have more than one psychiatric disorder. First-degree relatives of compulsive
      buyers were more likely than comparison relatives to suffer from depression,
      alcoholism, and a drug use disorder and to suffer more psychiatric disorders in
      general. CONCLUSIONS: These results indicate that persons who report compulsive
      buying behavior, and their first-degree relatives, are more likely to have a
      higher prevalence of psychiatric disorder than are comparison subjects.

PMID- 9659865
TI  - Abortion: social context, psychodynamic implications.

PMID- 9659867
TI  - Medical illness burden, trait neuroticism, and depression in older primary care
      patients.
AB  - OBJECTIVE: The authors tested the hypotheses that medical illness burden is
      independently associated with depression and that this association is moderated
      by neuroticism. METHOD: Multiple regression techniques were used to determine the
      independent associations of medical burden and neuroticism with depression in a
      group of 196 subjects, 60 years of age and older, recruited from primary care
      settings. RESULTS: Medical burden and neuroticism were independently associated
      with major depression, depressive symptoms, and psychiatric dysfunction.
      CONCLUSIONS: These findings support models in which medical disorders may
      contribute directly to depression. At the same time, the role of neuroticism in
      later-life depression warrants further study.

PMID- 9659868
TI  - Verapamil for the treatment of acute mania: a double-blind, placebo-controlled
      trial.
AB  - OBJECTIVE: This study investigated the efficacy of verapamil in acute mania.
      METHOD: The study was a 3-week double-blind, random-assignment, parallel-group,
      placebo-controlled inpatient trial of verapamil for patients with acute mania. Of
      the 32 study patients, 15 were given placebo and 17 were given verapamil.
      RESULTS: Mean absolute change scores on the Mania Rating Scale at endpoint, with
      baseline scores as the covariates, did not differ between the verapamil and
      placebo groups. There were no significant differences between the two groups in
      age, sex, and presence of psychosis. CONCLUSIONS: The investigators found no
      benefit of verapamil over placebo in treating acute mania.

PMID- 9659869
TI  - Smoking cessation treatment for patients with schizophrenia.
AB  - OBJECTIVE: This study was an uncontrolled trial to assess the efficacy of a
      smoking cessation group program modified for individuals with schizophrenia.
      METHOD: Fifty outpatients with schizophrenia were divided into five groups who
      met separately for seven weekly sessions of a smoking cessation program. The
      subjects' schizophrenic and extrapyramidal symptoms were assessed before the
      group sessions began and after they had been completed. Assessments of smoking
      were made at those times and at 3-month and 6-month follow-ups. RESULTS: Forty
      two percent of the subjects had stopped smoking at the end of the group sessions;
      16% remained abstinent at 3 months, and 12% at 6 months. These changes were
      statistically significant. There was no change in the positive or negative
      symptoms of schizophrenia. CONCLUSIONS: The results suggest that it is possible
      for individuals with schizophrenia to stop smoking.

PMID- 9659870
TI  - Inverse relationship of perinatal complications and eye tracking dysfunction in
      relatives of patients with schizophrenia: evidence for a two-factor model.
AB  - OBJECTIVE: Because both smooth pursuit eye tracking dysfunction and obstetrical
      complications are significant risk factors for schizophrenia, the authors tested
      the predictions of a two-factor model of how eye tracking dysfunction and
      obstetrical complications covary in patients with schizophrenia, their siblings,
      and comparison subjects. METHOD: Psychiatric diagnoses, eye tracking dysfunction,
      and obstetrical complications noted in birth records were independently assessed
      in 18 patients with schizophrenia, 16 of their siblings without schizophrenia,
      and 49 comparison subjects with neither personal nor family histories of
      schizophrenia. RESULTS: As hypothesized, 1) the combination of eye tracking
      dysfunction and perinatal obstetrical complications discriminated patients with
      schizophrenia significantly from subjects without schizophrenia, including
      siblings of patients with schizophrenia, and 2) eye tracking dysfunction and
      perinatal obstetrical complications manifested a significant inverse association
      in the nonschizophrenic siblings of patients with schizophrenia. CONCLUSIONS:
      These results support a two-factor model in which obstetrical complications often
      interact with genetic liability, indicated by eye tracking dysfunction, to
      produce schizophrenia.

PMID- 9659871
TI  - Effect of acute metabolic stress on pituitary-adrenal axis activation in patients
      with schizophrenia.
AB  - OBJECTIVE: Although several lines of evidence suggest that stress plays a role in
      the course of schizophrenia, studies that have assessed stress-relevant
      neurobiological measures have not produced consistent results. The authors
      examined the effects of acute metabolic stress induced by 2-deoxy-D-glucose (2
      DG) on pituitary-adrenal axis activation. METHOD: Thirteen patients with
      schizophrenia and 11 healthy comparison subjects were administered
      pharmacological doses of 2-DG (40 mg/kg). The subjects' arterial plasma was then
      assayed for levels of adrenocorticotropic hormone (ACTH) and cortisol. RESULTS: 2
      DG induced significant increases in the measured hormones in both groups, and
      ACTH elevations were significantly greater in patients with schizophrenia than in
      comparison subjects. CONCLUSIONS: Patients with schizophrenia have an exaggerated
      ACTH response to acute metabolic stress exposure.

PMID- 9659872
TI  - Cultural and linguistic barriers to mental health service access: the deaf
      consumer's perspective.
AB  - OBJECTIVE: The authors investigated knowledge, attitudes, and beliefs about
      mental illness and providers held by a group of deaf adults. METHOD: The American
      Sign Language interviews of 54 deaf adults were analyzed. RESULTS: Recurrent
      themes included mistrust of providers, communication difficulty as a primary
      cause of mental health problems, profound concern with communication in therapy,
      and widespread ignorance about how to obtain services. CONCLUSIONS: Deaf
      consumers' views need due consideration in service delivery planning. Outreach
      regarding existing programs is essential.

PMID- 9659873
TI  - Gabapentin as a potential treatment for anxiety disorders.

PMID- 9659874
TI  - Intravenous clomipramine for a schizophrenic patient with obsessive-compulsive
      symptoms.

PMID- 9659875
TI  - Hypersalivation coincident with olanzapine treatment.

PMID- 9659876
TI  - Screening for depression in elderly patients.

PMID- 9659877
TI  - Pulse clomipramine for depressed adolescents.

PMID- 9659878
TI  - Intellectual decline in schizophrenic patients.

PMID- 9659879
TI  - Denatured venous homograft as an arterial substitute in civilian vascular
      injuries. Thirty months' experience.
AB  - OBJECTIVES: Autologous saphenous vein (ASV) for arterial reconstruction, in
      vascular limb injuries is the graft material of choice. Denatured saphenous vein
      homograft (DSVH), thanks to its characteristics of readily available autologous
      biological prosthesis, has been proposed as alternative. We report our
      prospective experience with DSVH employed for arterial reconstruction in civilian
      limb vascular injuries. MATERIALS: From January 1994 to June 1996, DSVH was
      implanted in 16 male patients (pts.) treated for arterial civilian injuries of
      eight upper limbs and eight lower limbs. METHODS: In 14 cases it was performed as
      an interposition graft and in two cases a bypass. We performed a 30-month follow
      up and a 20-month mean follow-up. RESULTS: Four patients had graft thrombosis at
      the first postoperative week and were submitted to the replacement of the graft
      with reappearance of distal arterial pulse; one of them had graft failure at the
      fifth postoperative week and because the necrosis due to extensive soft tissue
      damage, he was submitted to limb amputation. After 30-months' follow-up we
      obtained 75% primary patency rate and 93% secondary patency rate. CONCLUSIONS: In
      the absence of suitable ASV, DSVH appears to be an interesting alternative for
      arterial repair in limbs in civilian vascular injuries.

PMID- 9659880
TI  - Relationship between abdominal aortic aneurysm wall compliance and clinical
      outcome: a preliminary analysis.
AB  - BACKGROUND: Aortic compliance, as measured by the pressure-strain elastic modulus
      (Ep) and stiffness (B), may allow a more precise estimate of abdominal aortic
      aneurysm rupture risk than size alone. AIM: To determine the relationships
      between AAA compliance, size, growth, and clinical outcome. METHODS: One-hundred
      and twelve patients with initially non-operated AAA (86 men, 26 women, mean age
      73 years), recruited from five centres, underwent baseline compliance
      measurements and were then followed for a median of 7 (range 2-18) months; 85
      patients underwent repeated measurements (median 3, range 2-5) 3-6-monthly over a
      median of 12 (range 3-18 months). RESULTS: Seven patients have ruptured and 16
      have undergone repair of non-ruptured AAA. AAA that ruptured had significantly
      lower Ep and B (more compliant). In AAA that ruptured or required repair there
      was an inverse relationship between diameter and Ep and B. In those undergoing
      repeated measurements AAA expansion was only associated with a significant
      increase in Ep and B in non-operated patients. CONCLUSIONS: Baseline AAA
      compliance was significantly related to rupture and the future requirement for
      operative repair. Failure of compliance to increase with size may be a marker for
      rapid growth, developmental symptoms and rupture.

PMID- 9659881
TI  - A 10-year follow-up of patients presenting with ischaemic rest pain of the lower
      limbs.
AB  - OBJECTIVES: To determine the 10-year outcome of patients presenting with rest
      pain. METHODS: One hundred and three consecutive patients presenting with
      ischaemic rest pain in 1987 were followed up after 10 years. Hospital notes,
      death certificates and telephone interviews with patients were used to determine
      outcome. RESULTS: Follow-up data is available for 97 (94%) patients. Thirteen
      patients are alive (13.7%) after 10 years, 12 presented with rest pain alone and
      one had ulceration. Three of these had amputation. The commonest cause of death
      was myocardial infarction (n = 21, 25%). In those who had died, the median age of
      onset of symptoms was 72 years (49-93) for rest pain, 74 years (56-87) for
      ulceration and 71.5 years (45-85) for gangrene. Their survival after admission
      was a mean of 39 months with rest pain, 33 months with ulceration and 42 months
      with gangrene. The overall 5-year survival was 31% and the 10-year survival 13%.
      CONCLUSION: Patients presenting with ischaemic rest pain have a poor prognosis.
      The presence or absence of ulceration or gangrene does not influence the outcome.
      Most patients die from smoking-related diseases.

PMID- 9659882
TI  - Reducing the operative trauma in aortoiliac reconstructions--a prospective study
      to evaluate the role of video-assisted vascular surgery.
AB  - OBJECTIVE: To evaluate the role of the surgical access with regard to the
      generation of proinflammatory proteins in patients with aortoiliac occlusive
      disease. DESIGN: Non-random, prospective study of patients undergoing an
      aortobifemoral bypass procedure. MATERIALS: Twenty-six patients were divided into
      three groups. In the first group of eight patients, a transperitoneal median
      laparotomy was used. The second group comprised 10 patients in whom a
      laparoscopically assisted extraperitoneal minilaparotomy was performed and, in
      the third group, eight patients were operated on using a retroperitoneal access.
      METHODS: Biochemical analysis of acute phase proteins and the cytokines
      interleukin-6 (Il 6), interleukin-8 (Il 8) and tumour necrosis factor (TNF).
      RESULTS: Aortic cross-clamp and total operative time were significantly longer in
      the laparoscopic group. After 24 h Il-6 concentrations were significantly higher
      in the transperitoneal (p < 0.05) and the retroperitoneal group (p < 0.006).
      After 6 h there was a reduced Il-8 concentration in the laparoscopic group
      compared to patients with a standard retroperitoneal access. Neither TNF nor
      acute phase proteins showed any significant alterations. CONCLUSION: Laparoscopic
      assisted vascular surgery allows for a smaller incision and reduces the surgical
      trauma, as it is reflected by interleukin levels.

PMID- 9659883
TI  - In vivo experiments with mesothelial cell seeded ePTFE vascular grafts.
AB  - OBJECTIVES: To investigate the influence of mesothelial cell (MC) seeding on
      patency and neointimal formation of small diameter ePTFE grafts in a canine
      model. MATERIALS AND METHODS: MC were isolated from the omentum, cultured, seeded
      on fibronectin-coated ePTFE grafts (4 cm, 4 mm ID), and implanted in the carotid
      artery of five Beagle dogs. Each dog also received a non-seeded control graft.
      Patency was assessed by palpation immediately after implantation, and non
      invasively by magnetic resonance angiography (MRA) after 1 week and just prior to
      sacrifice (4 weeks). Intimal thickness was quantified on histological sections by
      use of computer-aided morphometry. RESULTS: All grafts were patent after
      implantation. After 1 week, MRA showed the loss of lumen diameter in two seeded
      grafts. After 4 weeks, two seeded grafts were occluded, one seeded graft was
      severely stenosed, and all others were without angiographic lumen reduction.
      Histology and morphometry confirmed that two seeded grafts were occluded, and
      demonstrated that the other three seeded grafts showed significantly more intima
      formation (0.22-1.34 mm) than the control grafts (< 0.08 mm; p < 0.01).
      CONCLUSIONS: The MC seeding process decreases patency and increases neointimal
      formation of small diameter ePTFE grafts in dogs and does not seem to be useful
      for reduction of graft thrombogenicity.

PMID- 9659884
TI  - Intra- and interobserver variability in ultrasound measurements of abdominal
      aortic diameter. The Tromso Study.
AB  - OBJECTIVES: To assess the variability of ultrasonographic measurements at
      different levels of the abdominal aorta. DESIGN: Reproducibility study as part of
      a population health screening for abdominal aortic aneurysm. MATERIALS AND
      METHODS: In 1994/1995 a total of 6892 subjects underwent ultrasound examination
      of the abdominal aorta. Variability of measurements was assessed in the beginning
      and end of the survey period by inviting 112 randomly selected participants to a
      second ultrasound scan within 3 weeks of the first scan. The subjects were
      examined by an experienced radiologist and three sonographers who had been given
      a short course in ultrasonography. All examiners were blinded to each other's
      results. RESULTS: Variability was similar in the beginning and end of the survey
      period. Both the intra- and interobserver variability were less than 4 mm for all
      sonographers in measurements of maximal infrarenal aortic diameter, and
      variability was similar for measurements in the anterior-posterior and transverse
      plane. Variability was greater for measurements at the renal level than aortic
      bifurcation level. The radiologist had lower variability than the other
      sonographers. CONCLUSION: Ultrasound measurements of the maximal diameter can be
      obtained with a high degree of accuracy. Inexperienced sonographers may achieve
      acceptable performance given appropriate training and surveillance.

PMID- 9659885
TI  - Complications of standard elective abdominal aortic aneurysm repair.
AB  - OBJECTIVE: To evaluate complications of standard elective repair of infrarenal
      abdominal aortic aneurysms. DESIGN: Prospective multicentre study. MATERIALS: Two
      hundred and ninety-one consecutive patients undergoing standard elective surgery
      for an infrarenal aortic aneurysm. METHODS: Recording adverse events according to
      the recommendations of the Ad Hoc Committee on Reporting Standards. RESULTS:
      Seventy-five patients (26%) experienced some complication following elective
      aortic aneurysm surgery. Twenty-two patients had a mild complication (7.6%, 95%
      C.I. 4.8-11.2%), 27 a moderate (9.3%, 95% C.I. 6.2-13.2%) and 26 patients had a
      severe and/or fatal complication (8.9%, 95% C.I. 5.9-12.8%). The in-hospital
      mortality was 4.1% (12 patients, 95% C.I. 2.2-7.1%). Cardiac failure was the
      commonest primary cause for death (58%). Twenty-two per cent of the patients had
      a non-fatal complication: the most frequent being pulmonary (10%) and cardiac
      (10%). Patients with a history of cardiac events had a five times higher risk of
      a fatal outcome (95% C.I. 1.1-24.0) and a two and a half times higher risk of any
      severe fatal or non-fatal complication (95% C.I. 1.0-6.5). Other risk factors
      were advancing age and the presence of pulmonary disease. CONCLUSIONS: In
      addition to mortality, morbidity figures of standard aneurysm operations are
      important, as well as associated risk factors. This is especially true when
      evaluating early repair of small aneurysms and new endovascular techniques.

PMID- 9659886
TI  - Accuracy of carotid duplex is laboratory specific and must be determined by
      internal audit.
AB  - OBJECTIVE: To assess the accuracy of carotid duplex in a single vascular
      laboratory at the prediction of an angiographic 70% internal carotid artery
      stenosis. DESIGN: A retrospective review of all patients who underwent both
      carotid duplex and angiography in a 1-year period at a vascular unit which
      participates in the ACST trial. METHODS: Peak systolic velocity was used as a
      primary end-point in carotid duplex examinations with a PSV > 130 cm/s used as an
      indication for angiographic assessment. Biplanar arch aortography and selective
      carotid catheterisation were performed as indicated and diameter reduction
      calculated by the ECST method. RESULTS: The sensitivity of 130 cm/s for the
      detection of a 70% stenosis was 96% and the specificity 67%. If a PSV of 250 cm/s
      were used the sensitivity would be only 37% and specificity 96%. CONCLUSIONS:
      Applying duplex criteria from one centre to another is inappropriate. Laboratory
      specific audit of duplex and angiography is essential before deciding to abandon
      preoperative angiography for carotid disease.

PMID- 9659887
TI  - Local application of recombinant active-site inhibited human clotting factor VIIa
      reduces thrombus weight and improves patency in a rabbit venous thrombosis model.
AB  - OBJECTIVE: To study whether locally administered recombinant inactivated human
      coagulation factor VIIa (FFR-rFVIIa) would reduce the thrombus formation and
      improve patency in an experimental venous thrombosis model without inducing
      systemic changes in the coagulation. DESIGN: Experimental double-dummy randomised
      study. MATERIALS: In 20 healthy New Zealand White rabbits both jugular veins were
      exposed under general anaesthesia. METHODS: The thrombi were induced in a 10 mm
      long jugular vein segment with a combination of chemical destruction of the
      intima and a restriction of the bloodflow. Each segment was treated with either
      FFR-rFVIIa or placebo injected directly into the vein. RESULTS: 1.5 mg topically
      applied FFR-rFVIIa significantly reduced the thrombus weight (p < 0.001). The 30
      and the 120 min patency tests were significantly improved (p < 0.05 and p <
      0.001, respectively) Plasma analyses (APTT, dilute-TF time, FVII protein) were
      evaluated as baseline, 3 min after declamping and at sacrifice. No prolongation
      of the clotting times were seen. FFR-rFVIIa protein was detected in minute
      amounts (ng/ml); however, this was not enough to prolong the dilute-TF time.
      CONCLUSIONS: Local application of recombinant active-site inhibited human FVIIa
      reduced both thrombus weight and improved patency significantly in an
      experimental venous thrombosis model without affecting the systemic clotting
      times.

PMID- 9659888
TI  - Retrograde balloon angioplasty of brachiocephalic or common carotid artery
      stenoses at the time of carotid endarterectomy.
AB  - OBJECTIVES: This study was performed to demonstrate the value and durability of
      intraoperative retrograde angioplasty for stenotic lesions of the aortic arch
      branches at the time of carotid endarterectomy for the treatment of tandem
      proximal and bifurcation carotid lesions. DESIGN: Retrospective analysis of the
      clinical data. METHODS: Forty-four patients were included in this study when they
      presented with symptomatic extracranial vascular disease due to stenosis of both
      a proximal aortic arch branch and carotid bifurcation disease. Tandem disease was
      detected in the vascular laboratory and confirmed by angiography. Each patient
      was subjected to conventional carotid endarterectomy, and at the time of
      operation, the proximal lesion was subjected to transluminal angioplasty through
      the endarterectomy arteriotomy (brachiocephalic 24; left common carotid 15; right
      common carotid artery five). Patients were then followed up clinically and by non
      invasive tests at 6-monthly intervals. RESULTS: Forty-three successful
      dilatations were achieved. The single initial technical failure was due to heavy
      calcification of a brachiocephalic artery. In the follow-up period restenosis was
      noted in four patients. All restenosis occurred within 24 months. No restenosis
      at the angioplasty site was noted on subsequent follow-up of the remaining 39
      patients. No perioperative stroke or death was encountered. A surprisingly high
      mortality rate was noted on follow-up in this group of patients, suggesting the
      presence of more aggressive and advanced diffuse vascular disease. CONCLUSION:
      Retrograde intraoperative angioplasty of the proximal component of a tandem
      extracranial lesion has in this series proven to be a safe and durable
      therapeutic option. This technique has an acceptable restenosis rate in a subset
      of patients who have been demonstrated to have a shortened life expectancy and a
      high mortality rate in the follow-up period.

PMID- 9659889
TI  - Role of surgical techniques and operative findings in cranial and cervical nerve
      injuries during carotid endarterectomy.
AB  - OBJECTIVE: To establish the incidence of cranial and cervical nerve injuries
      during CEA and their relationship to different surgical techniques and operative
      findings. DESIGN: A prospective study. PATIENTS AND METHODS: From January 1994 to
      April 1995, 187 consecutive patients undergoing 190 CEAs were evaluated. Pre- and
      postoperative cranial and cervical nerve assessments were carried out by a single
      otolaryngologist, blinded to the operative technique and findings. Deficits
      lasting more than 12 months were defined as permanent. Logistic regression
      analysis was performed to evaluate the influence of surgical technique, type of
      anaesthesia, neck haematoma, and plaque extension on the onset of nerve injuries.
      RESULTS: Postoperatively, nerve lesions were identified in 51 CEAs (27%) and non
      neurological injuries (hemilaryngeal ecchymosis or oedema) causing postoperative
      dysphonia were present in 80 CEAs (42%). All non-neurological injuries were
      transient and 98% disappeared within 1 month of surgery. Thirteen (7%) nerve
      lesions were permanent, but none were disabling. Vagus nerve lesions were
      significantly associated with long (> 2 cm) carotid plaque (OR = 3.5; CI 1.09
      12.37; p = 0.03). Cervical branch lesions were associated with the presence of
      neck haematoma (OR = 1.9; CI 0.7-4.7; p = 0.05). The incidence of single cranial
      nerve injuries was higher in patch (OR = 2.7) and eversion (OR = 1.9) procedures
      than in primary closure. Multiple deficits (2 or more) were most frequent in
      eversion CEAs (OR = 2.8) and in cases complicated by neck haematoma (OR = 3.8).
      CONCLUSIONS: Cranial and cervical nerve lesions during CEA are common. However,
      our data showed that the majority of local complications are related to transient
      hemilaryngeal ecchymosis or oedema and, when permanent, are neither clinically
      relevant nor disabling at 1 year of follow up. Carotid plaque extension and neck
      haematoma appear to increase the incidence of cranial and cervical nerve lesions
      during CEA.

PMID- 9659890
TI  - Screening for abdominal aortic aneurysm: is opportunistic detection a realistic
      alternative?
AB  - OBJECTIVES: To determine whether abdominal aortic aneurysms (AAA) may be detected
      during investigation for concurrent disease and to assess whether opportunistic
      detection is a feasible alternative to a formal screening programme. DESIGN: A
      prospective review of previous investigations in subjects attending for aortic
      screening. MATERIALS AND METHODS: 276 men aged 65-80 attended the Chichester AAA
      screening programme. They were asked whether they had consulted their General
      Practitioner and whether they had undergone radiological investigation within the
      preceding 5 years. RESULTS: Two-hundred and sixty-one subjects had consulted
      their General Practitioner (94.6%) within the past 5 years. Fifty-six patients
      had been investigated with radiological imaging: in 22 cases (8.0%) the
      investigation had the potential to detect an AAA. The opportunistic detection
      rate was 0.4% (one AAA) in comparison to 12.0% for the screening programme (33
      AAA). Imaging investigations with the potential to pick up AAA failed to detect
      five out of six aneurysms in this group. CONCLUSIONS: Opportunistic screening for
      AAA is not a realistic alternative to a formal screening programme but may
      improve the detection rate in the community.

PMID- 9659891
TI  - Sources of error in intra-arterial pressure measurements across a stenosis.
AB  - OBJECTIVE: To investigate potential errors associated with different techniques
      of intra-arterial pressure measurement at angiography. MATERIALS AND METHODS: An
      experimental model of an arterial stenosis was developed. Experiments were
      performed to assess the relevance of catheter position, catheter direction and
      catheter type on the recorded intraluminal pressure. Transstenotic pressure
      gradients were recorded with and without angiographic catheters crossing the
      stenosis. RESULTS: At physiological flow rates angiographic catheter type does
      not influence the recorded pressure. At high flow rates through tight stenoses
      there is a significant catheter-related difference in recorded pressure adjacent
      to a stenosis. Downstream pressures may be altered by up to 85 mmHg when standard
      angiographic catheters are placed across a stenosis. CONCLUSION: The different
      techniques employed to measure pressure differences across a model stenosis may
      introduce significant errors up to 85 mmHg. Care must be taken when pressure
      measurements alone are used to interpret the clinical significance of a stenosis.
      In low flow conditions there may not be a detectable pressure gradient across a
      95% stenosis.

PMID- 9659892
TI  - Angioplasty balloon rupture: a way round the embolised fragment.

PMID- 9659893
TI  - Chronic arterial occlusion produced by hydatid cyst development in the lumen of
      the femoral artery.

PMID- 9659894
TI  - An acute lower limb ischaemia with an unusual cause.
AB  - Acute arterial occlusion associated with an abdominal aortic aneurysm can occur
      as a result of acute thrombosis or embolism from a mural thrombus of the
      aneurysm. We report here a case of an unusual association between a seat belt
      injury and an acute ischaemic leg in a patient known to have an abdominal aortic
      aneurysm. We also demonstrate some difficult dilemma related to the use of
      anticoagulation in patients with multiple injuries.

PMID- 9659895
TI  - Graft infection.

PMID- 9659896
TI  - Carotid endarterectomy.

PMID- 9659897
TI  - The best of molecular biology.

PMID- 9659898
TI  - 14-3-3sigma is a p53-regulated inhibitor of G2/M progression.
AB  - Exposure of colorectal cancer (CRC) cells to ionizing radiation results in a cell
      cycle arrest in G1 and G2. The G1 arrest is due to p53-mediated induction of the
      cyclin-dependent kinase inhibitor p21WAF1/CIP1/SDI1, but the basis for the G2
      arrest is unknown. Through a quantitative analysis of gene expression patterns in
      CRC cell lines, we have discovered that 14-3-3sigma is strongly induced by gamma
      irradiation and other DNA-damaging agents. The induction of 14-3-3sigma is
      mediated by a p53-responsive element located 1.8 kb upstream of its transcription
      start site. Exogenous introduction of 14-3-3sigma into cycling cells results in a
      G2 arrest. As the fission yeast 14-3-3 homologs rad24 and rad25 mediate similar
      checkpoint effects, these results document a molecular mechanism for G2/M control
      that is conserved throughout eukaryotic evolution and regulated in human cells by
      p53.

PMID- 9659899
TI  - The discoidin domain receptor tyrosine kinases are activated by collagen.
AB  - Two mammalian receptor tyrosine kinases (DDR1 and DDR2) have extracellular
      domains closely related to a D. discoideum lectin, discoidin, required for cell
      aggregation. Here, we show that the mammalian DDR receptors bind and are
      activated by specific types of collagen. Stimulation of DDR receptor tyrosine
      kinase activity requires the native triple-helical structure of collagen and
      occurs over an extended period of time. Collagen activation of DDR1 induces
      phosphorylation of a docking site for the Shc phosphotyrosine binding domain,
      whose presence is controlled by alternative splicing. Activation of DDR2 by
      collagen results in the up-regulation of matrix metalloproteinase-1 expression.
      These results suggest that the discoidin-related DDR tyrosine kinases are novel
      collagen receptors with the potential to control cellular responses to the
      extracellular matrix.

PMID- 9659900
TI  - An orphan receptor tyrosine kinase family whose members serve as nonintegrin
      collagen receptors.
AB  - Mammalian cells constantly monitor and respond to a myriad of extracellular
      signals, often by using cell surface receptors. Two important classes of cell
      surface receptors include the receptor tyrosine kinases, which recognize peptide
      growth factors such as insulin, and the integrins, which most often mediate
      binding to components of the extracellular matrix. We report that the collagens
      serve as ligands for the previously orphan family of discoidin domain-containing
      receptor-like tyrosine kinases. The unexpected realization that an extracellular
      matrix molecule can directly serve as a ligand for receptor tyrosine kinases
      provides an example of ligands shared by integrins and receptor tyrosine kinases,
      and this finding seems likely to change prevailing views about the mechanisms by
      which cells perceive and respond to the extracellular matrix.

PMID- 9659901
TI  - Differential roles of p300 and PCAF acetyltransferases in muscle differentiation.
AB  - PCAF is a histone acetyltransferase that associates with p300/CBP and competes
      with E1A for access to them. While exogenous expression of PCAF potentiates both
      MyoD-directed transcription and myogenic differentiation, PCAF inactivation by
      anti-PCAF antibody microinjection prevents differentiation. MyoD interacts
      directly with both p300/CBP and PCAF, forming a multimeric protein complex on the
      promoter elements. Viral transforming factors that interfere with muscle
      differentiation disrupt this complex without affecting the MyoD-DNA interaction,
      indicating functional significance of the complex formation. Exogenous expression
      of PCAF or p300 promotes p21 expression and terminal cell-cycle arrest. Both of
      these activities are dependent on the histone acetyltransferase activity of PCAF,
      but not on that of p300. These results indicate that recruitment of histone
      acetyltransferase activity of PCAF by MyoD, through p300/CBP, is crucial for
      activation of the myogenic program.

PMID- 9659902
TI  - Complementation cloning of S2P, a gene encoding a putative metalloprotease
      required for intramembrane cleavage of SREBPs.
AB  - We report the cloning of a gene, S2P, that encodes a putative metalloprotease
      required for intramembrane proteolysis of sterol-regulatory element-binding
      proteins (SREBPs) at Site-2. SREBPs are membrane-bound transcription factors that
      activate genes regulating cholesterol metabolism. The active NH2-terminal domains
      of SREBPs are released from membranes by sequential cleavage at two sites: Site
      1, within the lumen of the endoplasmic reticulum; and Site-2, within a
      transmembrane segment. The human S2P gene was cloned by complementation of mutant
      CHO cells that cannot cleave SREBPs at Site-2 and are cholesterol auxotrophs. S2P
      defines a new family of polytopic membrane proteins that contain an HEXXH
      sequence characteristic of zinc metalloproteases. Mutation of the putative zinc
      binding residues abolishes S2P activity. S2P encodes an unusual metalloprotease
      that cleaves proteins within transmembrane segments.

PMID- 9659903
TI  - Tricorn protease exists as an icosahedral supermolecule in vivo.
AB  - Tricorn protease is the core enzyme of a recently discovered modular proteolytic
      system. We present evidence that tricorn protease exists in vivo in the form of a
      higher-order assembly, namely as an icosahedral capsid. Its size exceeds that of
      many virus particles and represents by far the largest known homooligomeric
      enzyme complex. Each capsid is built from 20 copies of the tricorn hexameric
      toroid and thus has a molecular weight of 14.6 MDa. Three-dimensional
      reconstructions of ice-embedded capsids from electron micrographs show that it is
      hollow and has large void volumes in its wall. We suggest that the tricorn
      capsid, in addition to its intrinsic proteolytic activity, serves as the
      organizing center of a multienzyme complex.

PMID- 9659904
TI  - Crystal structure of the complex of diphtheria toxin with an extracellular
      fragment of its receptor.
AB  - We describe the crystal structure at 2.65 A resolution of diphtheria toxin (DT)
      complexed 1:1 with a fragment of its cell-surface receptor, the precursor of
      heparin-binding epidermal-growth-factor-like growth factor (HBEGF). HBEGF in the
      complex has the typical EGF-like fold and packs its principal beta hairpin
      against the face of a beta sheet in the receptor-binding domain of DT. The
      interface has a predominantly hydrophobic core, and polar interactions are formed
      at the periphery. The structure of the complex suggests that part of the membrane
      anchor of the receptor can interact with a hinge region of DT. The toxin molecule
      is thereby induced to form an open conformation conducive to membrane insertion.
      The structure provides a basis for altering the binding specificity of the toxin,
      and may also serve as a model for other EGF-receptor interactions.

PMID- 9659905
TI  - Domain interactions in E. coli SRP: stabilization of M domain by RNA is required
      for effective signal sequence modulation of NG domain.
AB  - The E. coli protein, Fth, binds to 4.5S RNA through its M domain to form the
      signal recognition particle (SRP). The other domain of Fth (NG) is a GTPase,
      which binds and is coordinately regulated by its receptor, FtsY. We find that the
      helical M domain is inherently flexible. Binding of 4.5S RNA to Fth stabilizes
      the M domain yet has little apparent effect on the binding of signal peptides.
      However, in the absence of the RNA, signal peptide binding results in a global
      destabilization of Fth, which is prevented by binding of 4.5S RNA. Signal peptide
      binding to isolated NG domain also causes a pronounced destabilization,
      implicating the NG domain in direct recognition of signal peptide.

PMID- 9659906
TI  - Site-specific ribonuclease activity of eukaryotic DNA topoisomerase I.
AB  - Type I topoisomerases alter DNA topology by cleaving and rejoining one strand of
      duplex DNA through a covalent protein-DNA intermediate. Here we show that
      vaccinia topoisomerase, a eukaryotic type IB enzyme, catalyzes site-specific
      endoribonucleolytic cleavage of an RNA-containing strand. The RNase reaction
      occurs via transesterification at the scissile ribonucleotide to form a covalent
      RNA-3'-phosphoryl-enzyme intermediate, which is then attacked by the vicinal 2'
      OH of the ribose sugar to yield a free 2', 3' cyclic phosphate product.
      Introduction of a single ribonucleoside at the scissile phosphate of an otherwise
      all-DNA substrate suffices to convert the topoisomerase into an endonuclease.
      Human topoisomerase I also has endoribonuclease activity. These findings suggest
      potential roles for topoisomerases in RNA processing.

PMID- 9659907
TI  - Transcription activation or repression by phage psi 29 protein p4 depends on the
      strength of the RNA polymerase-promoter interactions.
AB  - Phage psi 29 protein p4 activates the late A3 promoter and represses the early
      A2c promoter, in both cases by binding upstream from RNA polymerase (RNAP) and
      interacting with the C-terminal domain of the RNAP alpha subunit. To investigate
      how this interaction leads to activation at PA3 and to repression at PA2c, mutant
      promoters were constructed. We show that the position of protein p4 relative to
      that of RNAP, which is different at each promoter, does not dictate the outcome
      of the interaction. Rather, in the absence of a-35 consensus box for sigma A-RNAP
      activation was observed, while in its presence repression occurred. The results
      support the view that stabilization of RNAP at the promoter over a threshold
      level leads to repression.

PMID- 9659908
TI  - FMRP associates with polyribosomes as an mRNP, and the I304N mutation of severe
      fragile X syndrome abolishes this association.
AB  - Fragile X mental retardation is caused by the lack of FMRP, a selective RNA
      binding protein associated with ribosomes. A missense mutation, I304N, has been
      found to result in an unusually severe phenotype. We show here that normal FMRP
      associates with elongating polyribosomes via large mRNP particles. Despite normal
      expression and cytoplasmic mRNA association, the I304N FMRP is incorporated into
      abnormal mRNP particles that are not associated with polyribosomes. These data
      indicate that association of FMRP with polyribosomes must be functionally
      important and imply that the mechanism of the severe phenotype in the I304N
      patient lies in the sequestration of bound mRNAs in nontranslatable mRNP
      particles. In the absence of FMRP, these same mRNAs may be partially translated
      via alternative mRNPs, although perhaps abnormally localized or regulated,
      resulting in typical fragile X syndrome.

PMID- 9659909
TI  - The mechanism of transcriptional synergy of an in vitro assembled interferon-beta
      enhanceosome.
AB  - A functional interferon-beta gene enhanceosome was assembled in vitro using the
      purified recombinant transcriptional activator proteins ATF2/c-JUN, IRF1, and
      p50/p65 of NF-kappa B. Maximal levels of transcriptional synergy between these
      activators required the specific interactions with the architectural protein HMG
      I(Y) and the correct helical phasing of the binding sites of these proteins on
      the DNA helix. Analyses of the in vitro assembled enhanceosome revealed that the
      transcriptional synergy is due, at least in part, to the cooperative assembly and
      stability of the complex. Reconstitution experiments showed that the formation of
      a stable enhanceosome-dependent preinitiation complex require cooperative
      interactions between the enhanceosome; the general transcription factors TFID,
      TFIIA, and TFIIB; and the cofactor USA. These studies provide a direct
      biochemical demonstration of the importance of the structure and function of
      natural multicomponent transcriptional enhancer complexes in gene regulation.

PMID- 9659910
TI  - The effect of distance on long-range chromatin interactions.
AB  - We have used gene competition to distinguish between possible mechanisms of
      transcriptional activation of the genes of the human beta-globin locus. The
      insertion of a second beta-globin gene at different points in the locus shows
      that the more proximal beta gene competes more effectively for activation by the
      locus control region (LCR). Reducing the relative distance between the genes and
      the LCR reduces the competitive advantage of the proximal gene, a result that
      supports activation by direct interaction between the LCR and the genes.
      Visualization of the primary transcripts shows that the level of transcription is
      proportional to the frequency of transcriptional periods and that such periods
      last approximately 8 min in vivo. We also find that the position of the beta
      globin gene in the locus is important for correct developmental regulation.

PMID- 9659911
TI  - Role of nucleosome remodeling factor NURF in transcriptional activation of
      chromatin.
AB  - The Drosophila nucleosome remodeling factor (NURF) is a protein complex of four
      subunits that assists transcription factor-mediated perturbation of nucleosomes
      in an ATP-dependent manner. We have investigated the role of NURF in activating
      transcription from a preassembled chromatin template and have found that NURF is
      able to facilitate transcription mediated by a GAL4 derivative carrying both a
      DNA binding and an activator domain. Interestingly, once nucleosome remodeling by
      the DNA binding factor is accomplished, a high level of NURF activity is not
      continuously required for recruitment of the general transcriptional machinery
      and transcription for at least 100 nucleotides. Our results provide direct
      evidence that NURF is able to assist gene activation in a chromatin context, and
      identify a stage of NURF dependence early in the process leading to
      transcriptional initiation.

PMID- 9659912
TI  - Terminal intron dinucleotide sequences do not distinguish between U2- and U12
      dependent introns.
AB  - Two types of eukaryotic nuclear introns are known: the common U2-dependent class
      with /GU and AG/ terminal intron dinucleotides, and the rare U12-dependent class
      with /AU and AC/ termini. Here we show that the U12-dependent splicing system can
      splice introns with /GU and AG/ termini and that such introns occur naturally.
      Further, U2-dependent introns with /AU and AC/termini also occur naturally and
      are evolutionarily conserved. Thus, the sequence of the terminal dinucleotides
      does not determine which spliceosomal system removes an intron. Rather, the four
      classes of introns described here can be sorted into two mechanistic classes (U2-
      or U12-dependent) by inspection of the complete set of conserved splice site
      sequences.

PMID- 9659913
TI  - The ERO1 gene of yeast is required for oxidation of protein dithiols in the
      endoplasmic reticulum.
AB  - We describe a conserved yeast gene, ERO1, that is induced by the unfolded protein
      response and encodes a novel glycoprotein required for oxidative protein folding
      in the ER. In a temperature-sensitive ero1-1 mutant, newly synthesized
      carboxypeptidase Y is retained in the ER and lacks disulfide bonds, as shown by
      thiol modification with AMS. ERO1 apparently determines cellular oxidizing
      capacity since mutation of ERO1 causes hypersensitivity to the reductant DTT,
      whereas overexpression of ERO1 confers resistance to DTT. Moreover, the oxidant
      diamide can restore growth and secretion in ero1 mutants. Genetic tests
      distinguish the essential function of ERO1 from that of PDI1. We show that
      glutathione is not required for CPY folding and conclude that Ero1p functions in
      a novel mechanism that sustains the ER oxidizing potential, supporting net
      formation of protein disulfide bonds.

PMID- 9659914
TI  - Ero1p: a novel and ubiquitous protein with an essential role in oxidative protein
      folding in the endoplasmic reticulum.
AB  - The structure of many proteins entering the secretory pathway is dependent on
      stabilization by disulfide bonds. To support disulfide-linked folding, the
      endoplasmic reticulum (ER) must maintain a strongly oxidizing environment
      compared to the highly reduced environment of the cytosol. We report here the
      identification and characterization of Ero1p, a novel and essential ER-resident
      protein. Mutations in Ero1p cause extreme sensitivity to the reducing agent DTT,
      whereas overexpression confers DTT resistance. Strikingly, compromised Ero1p
      function results in ER retention of disulfide-stabilized proteins in a reduced,
      nonnative form, while not affecting structural maturation of a disulfide-free
      protein. We conclude that there exists a specific cellular redox machinery
      required for disulfide-linked protein folding in the ER and that Ero1p is an
      essential component of this machinery.

PMID- 9659916
TI  - A function for monoubiquitination in the internalization of a G protein-coupled
      receptor.
AB  - Modification of an S. cerevisiae G protein-coupled receptor with ubiquitin is
      required for its ligand-stimulated internalization. We now demonstrate that
      monoubiquitination on a single lysine residue is sufficient to signal receptor
      internalization, a modification distinct from that required for proteasome
      recognition. Formation of a polyubiquitin chain is not necessary, as demonstrated
      by the ability of mutant ubiquitins that lack lysine residues to serve as
      efficient internalization signals. Fusion of ubiquitin in-frame to a receptor
      that lacks cytoplasmic tail lysines also promotes rapid receptor internalization,
      indicating that ubiquitin itself and not a specific type of linkage to the
      receptor acts as an internalization signal. Thus, we have defined a cellular
      function for monoubiquitination in alpha-factor receptor endocytosis.

PMID- 9659915
TI  - PAK kinases are directly coupled to the PIX family of nucleotide exchange
      factors.
AB  - The PAK family of kinases are regulated through interaction with the small
      GTPases Cdc42 and Rac1, but little is known of the signaling components
      immediately upstream or downstream of these proteins. We have purified and cloned
      a new class of Rho-p21 guanine nucleotide exchange factor binding tightly through
      its N-terminal SH3 domain to a conserved proline-rich PAK sequence with a Kd of
      24 nM. This PAK-interacting exchange factor (PIX), which is widely expressed and
      enriched in Cdc42- and Rac1-driven focal complexes, is required for PAK
      recruitment to these sites. PIX can induce membrane ruffling, with an associated
      activation of Rac1. Our results suggest a role for PIX in Cdc42-to-Rac1
      signaling, involving the PIX/PAK complex.

PMID- 9659917
TI  - Point mutations in v-Myb disrupt a cyclophilin-catalyzed negative regulatory
      mechanism.
AB  - The c-Myb protein is controlled by intramolecular interactions, and point
      mutations can enhance its oncogenic activity. We tested whether conformational
      changes regulate c-Myb and found that Cyp-40, a widely distributed cyclophilin
      and peptidyl-prolyl isomerase, could inhibit c-Myb DNA binding activity.
      Inhibition by Cyp-40 required both its C-terminal protein-interaction domain,
      which bound specifically to c-Myb, and its N-terminal catalytic domain and was
      blocked by the competitive inhibitor cyclosporin A. Cyp-40 failed to bind or
      inhibit the oncogenic derivative v-Myb, which has a mutated Cyp-40 binding site.
      These results suggest that mutations in v-Myb allow it to evade a negative
      regulatory mechanism mediated by enzymes such as Cyp-40, and implicate peptidyl
      prolyl isomerases in the regulation of transcription, transformation, and
      differentiation.

PMID- 9659918
TI  - Molecular interaction between COP1 and HY5 defines a regulatory switch for light
      control of Arabidopsis development.
AB  - Arabidopsis COP1 acts as a light-inactivable repressor of photomorphogenic
      development, but its molecular mode of action remains unclear. Here, we show that
      COP1 negatively regulates HY5, a bZIP protein and a positive regulator of
      photomorphogenic development. Both in vitro and in vivo assays indicate that COP1
      interacts directly and specifically with HY5. The hyperphotomorphogenic phenotype
      caused by the over-expression of a mutant HY5, which lacks the COP1-interactive
      domain, supports the regulatory role of HY5-COP1 interaction. Further, HY5 is
      capable of directly interacting with the CHS1 minimal promoter and is essential
      for its light activation. We propose that the direct interaction with and
      regulation of transcription factors by COP1 may represent the molecular mechanism
      for its control of gene expression and photomorphogenic development.

PMID- 9659919
TI  - Three-dimensional architecture of the isolated yeast nuclear pore complex:
      functional and evolutionary implications.
AB  - We have calculated a three-dimensional map of the yeast nuclear pore complex
      (yNPC) from frozen-hydrated specimens, thereby providing a direct comparison with
      the vertebrate NPC. Overall, the smaller yNPC is comprised of an octagonal inner
      spoke ring that is anchored within the nuclear envelope by a novel membrane
      interacting ring. In addition, a cylindrical transporter is located centrally
      within the spokes and exhibits a variable radial expansion in projection that may
      reflect gating. The inner spoke ring, a transmembrane spoke domain, and the
      transporter are conserved between yeast and vertebrates; hence, they are required
      to form a functional NPC. However, significant alterations in NPC architecture
      have arisen during evolution that may be correlated with differences in nuclear
      transport regulation or mitotic behavior.

PMID- 9659920
TI  - A conserved domain within Arc1p delivers tRNA to aminoacyl-tRNA synthetases.
AB  - Two yeast enzymes that catalyze aminoacylation of tRNAs, MetRS and GluRS, form a
      complex with the protein Arc1p. We show here that association of Arc1p with MetRS
      and GluRS is required in vivo for effective recruitment of the corresponding
      cognate tRNAs within this complex. Arc1p is linked to MetRS and GluRS through its
      amino-terminal domain, while its middle and carboxy-terminal parts comprise a
      novel tRNA-binding domain. This results in high affinity binding of cognate tRNAs
      and increased aminoacylation efficiency. These findings suggest that Arc1p
      operates as a mobile, trans-acting tRNA-binding synthetase domain and provide new
      insight into the role of eukaryotic multimeric synthetase complexes.

PMID- 9659921
TI  - Human pre-mRNA cleavage factor Im is related to spliceosomal SR proteins and can
      be reconstituted in vitro from recombinant subunits.
AB  - Four polypeptides of 25, 59, 68, and 72 kDa copurify with the activity of human
      cleavage factor Im (CF Im) involved in pre-mRNA 3' end processing. We report here
      the cloning of the 25 and 68 kDa subunits and the reconstitution of functional CF
      Im25/68 from these two polypeptides. Several lines of evidence indicate that CF
      Im exists in at least two different forms. The 68 kDa polypeptide has a domain
      organization reminiscent of spliceosomal SR proteins. Analysis of the kinetics of
      the cleavage reaction indicates that interaction of CF Im with the RNA is one of
      the earliest steps in the assembly of the 3' end processing complex and
      facilitates the recruitment of other processing factors.

PMID- 9659922
TI  - U1 snRNP inhibits pre-mRNA polyadenylation through a direct interaction between
      U1 70K and poly(A) polymerase.
AB  - It has previously been shown in vivo that bovine papillomavirus represses its
      late gene expression via a 5' splice site sequence located upstream of the late
      polyadenylation signal. Here, the mechanism of repression is determined by in
      vitro analysis. U1 snRNP binding to the 5' splice site results in inhibition of
      polyadenylation via a direct interaction with poly(A) polymerase (PAP). Although
      the inhibitory mechanism is similar to that used in U1A autoregulation, U1A
      within the U1 snRNP does not contribute to PAP inhibition. Instead the U1 70K
      protein, when bound to U1 snRNA, both interacts with and inhibits PAP.
      Conservation of the U1 70K inhibitory domains suggests that polyadenylation
      regulation via PAP inhibition may be more widespread than previously thought.

PMID- 9659923
TI  - Independent ligand-induced folding of the RNA-binding domain and two functionally
      distinct antitermination regions in the phage lambda N protein.
AB  - The transcriptional antitermination protein N of bacteriophage lambda binds the
      boxB component of the RNA enhancer nut (boxA + boxB) and the E. coli elongation
      factor NusA. Efficient antitermination by N requires an RNA-binding domain (amino
      acids 1-22) and two activating regions for antitermination: a newly identified
      NusA-binding region (amino acids 34-47) that suppresses NusA's enhancement of
      termination, and a carboxy-terminal region (amino acids 73-107) that interacts
      directly with RNA polymerase. Heteronuclear magnetic resonance experiments
      demonstrate that N is a disordered protein. Interaction with boxB RNA induces
      only the RNA-binding domain of N to adopt a folded conformation, while the
      activating regions of the protein remain disordered in the absence of their
      target proteins.

PMID- 9659924
TI  - Recruitment of CBP/p300 by the IFN beta enhanceosome is required for synergistic
      activation of transcription.
AB  - Transcriptional activation of the IFN beta gene in response to virus infection
      requires the assembly of an enhanceosome, consisting of the transcriptional
      activators NF-kappa B, IRF1, ATF2/c-Jun, and the architectural protein HMG I(Y).
      The level of transcription generated by all of these activators is greater than
      the sum of the levels generated by individual factors, a phenomenon designated
      transcriptional synergy. We demonstrate that this synergy, in the context of the
      enhanceosome, requires a new protein-protein interaction domain in the p65
      subunit of NF-kappa B. Transcriptional synergy requires recruitment of the
      CBP/p300 coactivator to the enhanceosome, via a new activating surface assembled
      from the novel p65 domain and the activation domains of all of the activators.
      Deletion, substitution, or rearrangement of any one of the activation domains in
      the context of the enhanceosome decreases both recruitment of CBP and
      transcriptional synergy.

PMID- 9659925
TI  - Control of colinearity in AbdB genes of the mouse HoxD complex.
AB  - During development, vertebrate Hox genes are activated in a temporal and spatial
      sequence colinear with the position of the genes within their clusters. To
      investigate the mechanistic basis of this phenomenon, we used the ES cell
      technology and the loxP/Cre system to engineer a conditional fusion of the 5'
      exon of Hoxd-13 with the 3' exon of Hoxd-12. This hybrid transcription unit was
      regulated like Hoxd-11, with expression limits in the trunk, limbs, intestinal,
      and urogenital systems more anterior than those expected for either Hoxd-13 or
      Hoxd-12. An in vivo interspecies replacement by the fish homologous DNA fragment
      showed that anteriorization was not due to a distance effect, thus suggesting the
      presence of a regulatory element between Hoxd-13 and Hoxd-12 that may contribute
      to the establishment, early on, of a repressive state over these two genes.

PMID- 9659926
TI  - The scs and scs' insulator elements impart a cis requirement on enhancer-promoter
      interactions.
AB  - The Xenopus rRNA enhancer activates its cognate promoter when the two elements
      are placed on opposite rings of dimeric catenanes. Here we show that when scs
      elements flank either the enhancer or promoter in catenanes, the enhancer cannot
      activate the promoter on the ring in trans. A series of catenanes containing
      different permutations of the insulators, enhancer, and promoters shows that when
      insulators are present, the enhancer is permitted to a activate the promoter only
      when both elements are on the same piece of DNA with no intervening insulator.
      These results suggest that insulators have the potential to block enhancer
      promoter interactions between chromosomes and between independent topological
      domains within a chromosome.

PMID- 9659927
TI  - On the mechanism of RecA-mediated repair of double-strand breaks: no role for
      four-strand DNA pairing intermediates.
AB  - RecA protein will bind to a gapped duplex DNA molecule and promote a DNA strand
      exchange with a second homologous linear duplex. A double-strand break in the
      second duplex is efficiently bypassed in the course of these reactions. We
      demonstrate that the bypass of double-strand breaks is not explained by a
      mechanism involving homologous interactions between two duplex DNA molecules, but
      instead requires the ATP-mediated generation of DNA torsional stress brought
      about by the action of RecA. The results suggest new pathways for the repair of
      double-strand breaks and underline the need for new paradigms to explain the
      alignment of homologous DNAs during genetic recombination.

PMID- 9659928
TI  - Autoproteolytic activation of pro-caspases by oligomerization.
AB  - Initiation of apopotosis requires the conversion of procaspases to mature
      caspases. Here we show that oligomerization of pro-caspases is sufficient to
      induce proteolytic generation of mature caspase subunits and activation of their
      cell death activity. Deletion of the protein interaction motif DED from pro
      caspase-8 greatly suppresses its apoptotic activity. Cell death activity can be
      restored by oligomerization of pro-caspase-8 protease domains by two heterologous
      inducible oligomerization systems. Induced oligomerization also activates the
      apoptotic activity of pro-caspase-1 but not pro-caspase-3. In vitro,
      oligomerization leads to pro-caspase processing to from the mature caspase
      subunits; this processing requires the intrinsic caspase activity of zymogens and
      proceeds via a novel order of cleavage events.

PMID- 9659930
TI  - Maternal and zygotic expression of the endoderm-specific alkaline phosphatase
      gene in embryos of the ascidian, Halocynthia roretzi.
AB  - Alkaline phosphatase (AP) activity is expressed by endodermal cells of ascidian
      larvae. It was reported previously that the expression of AP activity is
      resistant to treatment with actinomycin D, a transcription inhibitor that
      inhibits the appearance of several other tissue-specific molecules and
      morphological markers of tissue formation in developing ascidians. The resistance
      of AP expression to actinomycin D treatment suggests that endodermal AP activity
      does not depend on zygotic transcription and that its appearance is mediated by
      the translational activation of maternal AP mRNA present in ascidian eggs.
      However, it was also shown that anucleate merogons do not develop AP activity. To
      directly examine whether maternal AP transcripts are present in the cytoplasm of
      eggs, we isolated a cDNA of an endoderm-specific AP in Halocynthia roretzi and
      examined the temporal and spatial expressions of this gene during embryogenesis
      using Northern blots and in situ hybridization. Maternal AP transcripts were
      detected in oocytes, cleaving-stage embryos, and in gastrulae, and endoderm
      specific AP transcripts dramatically increased about 14 times from the neurula
      stage to the larval stage in endoderm precursor cells. These results suggest that
      the differentiation of endoderm is primarily correlated with the activation of
      zygotic transcription of the AP gene, presumably by egg cytoplasmic factors,
      similar to how muscle and epidermis are believed to develop.

PMID- 9659929
TI  - FGF-2 alters the fate of mouse epiblast from ectoderm to mesoderm in vitro.
AB  - We have developed an in vitro differentiation assay to characterize the ability
      of peptide growth factors to induce differentiation in mouse epiblast. We report
      that culturing explants of mouse anterior epiblast, a tissue normally fated to
      give rise to neuroectoderm and surface ectoderm, in a serum-free, chemically
      defined medium with 10-50 ng/ml of FGF-2 induced gross changes in cell
      morphology. Treated cells adopted an elongated, flattened morphology but did not
      migrate from the explant. Instead, FGF-2-treated cells condensed into
      multicellular mounds or ridges. Immunocytochemistry showed that cells in treated
      explants expressed vimentin and in situ hybridization demonstrated that FGF-2
      induced the expression of brachyury, goosecoid, and myo-D in regions of treated
      explants displaying morphological differentiation. Control explants cultured with
      platelet-derived growth factor AA (PDGF AA), transforming growth factor-beta 1
      (TGF-beta 1), or in defined medium alone showed no morphological or biochemical
      differentiation. These results indicate that FGF-2 altered the fate of mouse
      anterior epiblast from ectoderm to mesoderm in vitro. Cell migration, which is
      characteristic of primitive streak mesoderm in vivo, was not induced by FGF-2 in
      these assays. However, the changes in morphology and the expression of mesodermal
      genes in vitro do support an early role for FGF signaling in the induction of
      mouse primitive streak mesoderm, as well as in later patterning events during
      embryogenesis.

PMID- 9659931
TI  - Gastrulation initiation in Caenorhabditis elegans requires the function of gad-1,
      which encodes a protein with WD repeats.
AB  - Gastrulation in Caenorhabditis elegans is normally initiated by inward migration
      of the two gut precursor (E) cells at the 26-cell stage. A strong loss-of
      function, temperature-sensitive, embryonic lethal mutation in the maternally
      required gene gad-1 (gastrulation defective) prevents gastrulation initiation. In
      embryos from homozygous mutant gad-1 (ct226) hermaphrodites reared at 25 degrees
      C, the E cells divide early with abnormal spindle orientations and fail to
      migrate into the embryo, and no subsequent gastrulation movements occur. These
      embryos continue to develop and differentiate the major cell types, but they
      undergo little morphogenesis. The temperature-sensitive period of the mutant is
      during early embryogenesis, prior to gastrulation onset. The predicted
      translation product of the cloned gad-1 gene includes six beta-transducin-related
      repeats of the WD motif, which has been implicated in protein-protein
      interactions. The ct226 mutation alters a conserved residue in one of these
      repeats. Injection of gad-1 antisense RNA into wild-type hermaphrodites mimics
      the mutant phenotype in progeny embryos. We conclude that the gad-1 gene product
      is required for initiation of gastrulation in C. elegans.

PMID- 9659932
TI  - Survival of patchwork melanoblasts is dependent upon their number in the hair
      follicle at the end of embryogenesis.
AB  - The recessive patchwork (pwk) mutation in mice is associated with a unique hair
      follicle phenotype. Mice homozygous for patchwork exhibit a variegated coat
      containing a mixture of white and fully pigmented hairs, but no partially
      pigmented hairs. We have investigated the etiology of this mutation. We report
      here that the white hairs result from the lack of melanocytes in the follicle. As
      indicated by the coat color pattern of patchwork<-->albino chimeras, the target
      cell for the patchwork mutation is the melanocyte and/or its precursor.
      Examination of these chimeras also suggested that patchwork does not act in a
      cell-autonomous manner. The colonization of the skin by melanoblasts in patchwork
      embryos was studied using a lacZ transgene. Melanoblasts die by apoptosis in hair
      follicles from homozygous pwk/pwk fetuses starting at embryonic day 18.5,
      indicating that patchwork acts from this stage. The combination of pwk and KitW
      ei, a mutation responsible for a reduced number of melanoblasts in the hair
      follicle, suggested that pwk gene product is necessary for low numbers of
      melanoblasts to survive and differentiate in the hair follicle from embryonic day
      18.5 onward. We conclude that the pigmented hairs on the coat of pwk/pwk mice may
      be attributed to a community effect among melanoblasts in the hair follicle at
      the end of embryogenesis.

PMID- 9659933
TI  - The Slug gene is not essential for mesoderm or neural crest development in mice.
AB  - The Slug gene encodes a zinc finger protein, homologous to the product of the
      Drosophila Snail gene, that is implicated in the generation and migration of both
      mesoderm and neural crest cells in several vertebrate species. We describe here
      the cloning and genetic analysis of the mouse Slug (Slugh) gene. Slugh encodes a
      269-amino-acid protein the shares 92% amino acid identity with the product of the
      chicken Slug gene. We have characterized Slugh gene expression during early mouse
      embryogenesis by whole mount in situ hybridization of Slugh mRNA and through
      detection of beta-galactosidase expression from an in-frame SlughIacZ allele
      generated through homologous recombination. Slugh expression is first detected in
      extraembryonic mesoderm and is later detected in many mesodermal subsets,
      although it is not detected in the primitive streak. In contrast to many other
      vertebrates, the mouse Slug gene is not expressed in premigratory neural crest
      cells but is expressed in migratory neural crest cells. Analysis of a targeted
      null mutation that deleted all Slugh coding sequences revealed that Slugh is not
      required for mesoderm formation or for neural crest generation, migration, or
      development in mice. These results indicate that neither the expression pattern
      nor the biological function of the Slug gene is conserved among all vertebrates.
      These data also raise interesting questions about the regulation of neural crest
      generation, which is one of the distinguishing characteristics of the vertebrate
      subphylum.

PMID- 9659934
TI  - The GATA-factor elt-2 is essential for formation of the Caenorhabditis elegans
      intestine.
AB  - The Caenorhabditis elegans elt-2 gene encodes a single-finger GATA factor,
      previously cloned by virtue of its binding to a tandem pair of GATA sites that
      control the gut-specific ges-1 esterase gene. In the present paper, we show that
      elt-2 expression is completely gut specific, beginning when the embryonic gut has
      only two cells (one cell cycle prior to ges-1 expression) and continuing in every
      cell of the gut throughout the life of the worm. When elt-2 is expressed
      ectopically using a transgenic heat-shock construct, the endogenous ges-1 gene is
      now expressed in most if not all cells of the embryo; several other gut markers
      (including a transgenic elt-2-promoter::lacZ reporter construct designed to test
      for elt-2 autoregulation) are also expressed ectopically in the same experiment.
      These effects are specific in that two other C. elegans GATA factors (elt-1 and
      elt-3) do not cause ectopic gut gene expression. An imprecise transposon excision
      was identified that removes the entire elt-2 coding region. Homozygous elt-2 null
      mutants die at the L1 larval stage with an apparent malformation or degeneration
      of gut cells. Although the loss of elt-2 function has major consequences for
      later gut morphogenesis and function, mutant embryos still express ges-1. We
      suggest that elt-2 is part of a redundant network of genes that controls
      embryonic gut development; other factors may be able to compensate for elt-2 loss
      in the earlier stages of gut development but not in later stages. We discuss
      whether elements of this regulatory network may be conserved in all metazoa.

PMID- 9659935
TI  - Contribution of retinoic acid receptor beta isoforms to the formation of the
      conotruncal septum of the embryonic heart.
AB  - To investigate the relative contribution of retinoic acid receptor (RAR)beta
      isoforms in conotruncal septation, RAR beta 1 and beta 3 were inactivated in the
      mouse. Mice lacking RAR beta 1 and beta 3 appear normal. Disruption of these
      isoforms in RAR alpha or RAR gamma null genetic backgrounds results in a high
      postpartum lethality. However, except for ocular defects found in RAR beta 1
      3/RAR gamma compound mutants, the double null mutants display only abnormalities
      seen in single null mutants. This probably reflects a functional redundancy with
      other RARs, most notably with RAR beta 2 which is five- to sixfold more abundant
      than RAR beta 1 and beta 3 and whose domain of expression is largely overlapping.
      The conotruncal ridges form normally in retinoid X receptor (RXR)alpha/RAR beta
      compound mutants but fail to fuse, apparently as a result of excessive apoptosis
      of mesenchymal cells. Additionally, many cardiomyocytes in the conotruncal wall
      of these mutants appear necrotic. Although RAR beta 1 and beta 3 are expressed
      specifically in the conotruncal ridges, failure of fusion of these structures is
      not more frequent in RXR alpha/RAR beta 1-3 double null mutants than in RXR alpha
      single null mutants. Similarly, the disruption of the sole RAR beta 2 isoform in
      a RXR alpha null genetic background does not result in an increase of the
      frequency of conotruncal septum agenesis. However, this agenesis is fully
      penetrant in RXR alpha/RAR beta +/- mutants, which reflects distinct role of RXR
      alpha:RAR beta 1 (and beta 3) and RXR alpha:RAR beta 2 heterodimers in promoting
      the survival of conotruncal mesenchymal cells. Unexpectedly, we discovered that,
      in wild-type embryos, the conotruncal mesenchyme is a major site of morphogenetic
      cell death and that conotruncal myocytes are occasionally necrotic. Thus,
      excessive cell death in the conotruncus is a potential cause of ventricular
      septal defects in humans.

PMID- 9659936
TI  - The inductive properties of mesoderm suggest that the neural crest cells are
      specified by a BMP gradient.
AB  - We have analyzed the role of mesoderm in the induction of the neural crest in
      Xenopus using expression of neural plate (Xsox-2) and neural crest (Xslug and
      ADAM). Conjugation experiments using different kinds of mesoderm together with
      embryonic dissection experiments suggest that the dorsolateral mesoderm is
      capable of specifically inducing neural crest cells. Neural crest markers can be
      induced in competent ectoderm at varying distances from the inducing mesoderm,
      with dorsal tissue inducing neural crest at a distance while dorsolateral tissue
      only induces neural crest directly in adjacent ectoderm. The results suggest that
      dorsal mesoderm has a high level of inducer and dorsolateral mesoderm has a lower
      level, consistent with a inductive gradient. We explored the possible role of BMP
      and noggin in the generation of such a hypothetical gradient and found that: (1)
      progressively higher levels of BMP activity are sufficient for the specification
      of neural plate, neural crest, and nonneural cells, respectively; (2)
      progressively higher levels of noggin are able to induce neural crest at greater
      distances from the source of inducer; and (3) modification of the levels of BMP
      activity causes induction of the neural crest in absence of neural plate,
      suggesting independent induction of these two tissues. We propose a model in
      which a gradient of BMP activity is established in the ectoderm by interaction
      between BMP in the ectoderm and BMP inhibitors in the mesoderm. Neural crest is
      induced when a threshold level of BMP is attained in the ectoderm. The
      dorsolateral mesoderm produces either BMP inhibitors or a specific neural crest
      inducer, with low BMP activity inducing neural plate while high BMP activity
      induces epidermis.

PMID- 9659937
TI  - Cells are added to the archenteron during and following secondary invagination in
      the sea urchin Lytechinus variegatus.
AB  - In the present investigation, nuclei of endodermal cells, primary and secondary
      mesenchyme cells (PMCs and SMCs), and small micromere descendants (SMDs) of the
      sea urchin Lytechinus variegatus were counted and mapped at five developmental
      stages, ranging from primary invagination to pluteus larva. The archenteron and
      its derivatives were measured three dimensionally with STERECON analytical
      software. For the first time SMC production is included in the kinetic analysis
      of archenteron formation. While the archenteron lumen doubled in length during
      secondary invagination, the number of archenteron cells increased by at least 38%
      (over 50% when SMCs that emigrated from the tip of the archenteron were
      included). The volume of the archenteron epithelial wall plus the volume of 17
      new SMCs increased by 40% over the equivalent volumes at the end of primary
      invagination. Because secondary invagination involves the addition of archenteron
      cells and an increase in volume of the archenteron epithelium, we conclude that
      secondary invagination is not accomplished simply by the rearrangement and
      reshaping of the primary archenteron cells. Both archenteron cell number and wall
      volume continued to increase at the same rates from the end of secondary
      invagination until the 27-h prism stage, although the lumen lengthened more
      slowly. SMCs were also produced at a constant rate from primary invagination
      until the prism stage. Because the production of both endodermal and mesodermal
      cells continues until the late prism stage, we conclude that gastrulation
      (defined as the establishment of the germ layers) also extends into the late
      prism stage.

PMID- 9659938
TI  - Promotion of the development of enteric neurons and glia by neuropoietic
      cytokines: interactions with neurotrophin-3.
AB  - Neurotrophin-3 (NT-3) is known to promote enteric neuronal and glial development.
      Ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) were
      investigated to test the hypothesis that the development of subsets of enteric
      neurons and/or glia is also affected by a neuropoietic cytokine, by itself, or
      together with NT-3. Crest-derived cells, immunoselected from the fetal rat gut
      (E14) with antibodies to p75NTR, were found by RT-PCR and immunocytochemistry
      (after culture) to express both alpha (CNTER alpha) and beta components (gp130
      and LIFR beta) of the tripartite CNTF receptor. In situ, myenteric ganglia below
      the esophagus were CNTFR alpha-immunoreactive by E16-E18. In vitro, CNTF and LIF
      induced in crest-derived cells nuclear translocation of STAT3 (signal transducer
      and activator of transcription 3), a concentration-dependent increase in
      expression of neuronal or glial markers, and a decrease in expression of the
      precursor marker, nestin. LIFR beta was expressed by more cells than CNTFR alpha;
      therefore, although the factors were equipotent, the maximal effect of LIF >
      CNTF. The cytokines and NT-3 were additive in promoting neuronal but not glial
      development. Specifically, the development of neurons expressing NADPH-diaphorase
      activity (an early marker found in inhibitory motor neurons) was promoted by CNTF
      and NT-3. These observations support the idea that a ligand for the tripartite
      CNTF receptor complex plays a role in ENS development.

PMID- 9659939
TI  - A sperm chemoattractant is released from Xenopus egg jelly during spawning.
AB  - Although the jelly layers surrounding amphibian eggs are known to be essential to
      fertilization, no biological activities have been reported for jelly
      macromolecules in any vertebrate. Here we provide evidence that the jelly
      surrounding Xenopus laevis eggs releases a small diffusible protein into the
      surrounding media that serve as sperm chemoattractant. Using video microscopy we
      find that Xenopus sperm will preferentially turn toward and contact a glass
      capillary filled with egg jelly extract. In experiments using a two-chamber
      bioassay device we find that egg jelly extracts are capable of stimulating sperm
      movement across a membrane barrier sixfold over controls. This activity is not
      observed in materials unrelated to egg jelly and the response of sperm to egg
      jelly extract is clearly chemotactic rather than chemokinetic. A concentration
      gradient of the extract is absolutely necessary, and the chemotactic activity of
      the extract exhibits a biphasic dose dependence similar to that of chemotactic
      agents in other systems. We have been able to characterize the factor as being a
      heat-stable protein about 10 kDa in size. This study, therefore, provides the
      first clear evidence for a diffusible sperm chemoattractant in a nonhuman
      vertebrate, as well as the first demonstration of a physiological role for egg
      jelly macromolecules in Xenopus fertilization.

PMID- 9659941
TI  - Chemoradiotherapy interactions in the central nervous system.

PMID- 9659940
TI  - Radiation injury to the central nervous system.

PMID- 9659942
TI  - Magnetic resonance imaging of the brain: relationship between structure and
      function.
AB  - Contemporary brain-imaging methods permit exquisite 2-D and 3-D image analyses
      that can result in quantification of any given structure, lesion, or pathological
      state provided certain pixel boundaries can be identified on the computerized
      image. Several examples of the methods for image analysis and their display are
      provided here along with a review of the literature on their clinical and
      empirical use.

PMID- 9659943
TI  - Memory and attention after childhood brain tumors.

PMID- 9659944
TI  - Function-specific neuropsychological assessment.

PMID- 9659945
TI  - Theoretical issues pertinent to measurement of quality of life.

PMID- 9659946
TI  - Evaluation of quality of life of childhood cancer survivors: a methodological
      conundrum.
AB  - QOL assessment in pediatric oncology is seriously understudied, especially
      compared with the adult population. The limited progress is due to the
      methodological complexity of the task, which should not be viewed as
      insurmountable. Given a precise study question, the methodological issues can be
      clarified simply, piece by piece. Researchers must consider very carefully the
      specific characteristics that define a study population in order to choose an
      instrument that is domain-appropriate and valid for the assessment paradigm. The
      first priority should be that a researcher must identify the means of accessing
      the information of interest. In the pediatric population, information about
      children's status may be elicited from parents, medical personnel, teachers, or
      the children themselves. Clearly, the type of instrument to be used for
      assessment is dependent on the choice of reporter. Researchers must also account
      for developmental age and disease; in assessing generic and disease-specific
      functioning, the "functional scale" against which an individual is compared must
      implicitly reflect the types of activities and/or levels of functioning that are
      realistic norms for the patient. Equally important is the analysis of independent
      domains in order to characterize the dynamics/divergence of clinical status and
      functional status. What are the merits of conducting QOL research for the
      pediatric cancer-survivor population? The policy implications are profound and
      pervasive both for the individual survivors (regarding treatment, care, and
      his/her ultimate ability to reintegrate into society) and for society (regarding
      resource allocation, cost planning, and productivity). Commensurate with the
      rapid advancement of oncologic therapy, there is now an expanding cohort of
      pediatric cancer survivors. Current estimates suggest that, by the turn of the
      century, 200,000 children will be in this category. The long-term survivorship of
      this cohort is still poorly defined. However, as the survivors mature, it is
      likely that their needs will evolve as well-whether for treatment of secondary
      malignancies, long-term morbidities, and fertility issues or for
      neuropsychological dysfunction, emotional counseling, or occupational issues.
      Children, as survivors, are unique, in that their future (the context within
      which long-term outcome is defined) spans decades. Based on a median age at
      diagnosis of 6 years, survivors can expect to live an additional 66 years. From a
      cost or policy perspective, children represent enormous future potential. The
      implications of children's long-term outcomes must be considered regarding the
      change in future potential secondary to survivorship. Pediatric QOL research
      plays a role both inside and outside the health care system. Clearly, in the
      provision of health care, QOL data may be used to improve or modify patient care
      by supplementing information about the clinical status of individual patients.
      Information about an individual's general functioning, particularly as it
      diverges from disease-specific functioning, complements clinical data to
      facilitate comprehensive care. Information about the long-term outcomes of
      pediatric cancer, as a whole, will influence the policies of health care
      institutions and the allocation of health care resources. By expanding the scope
      of survivorship (or cure) to include long-term clinical and general "costs" the
      "cost of cure" is shifted: this shift will ultimately impact estimations of cost
      effectiveness, with ramifications for the evaluation of hospital-wide protocols,
      utilization priorities, and cost policies. Outside of the hospital, the
      implications of QOL research are equally ubiquitous. Pediatric survivors will
      live an estimated 7 decades after "cure," during which time they will exist
      almost entirely outside the realm of health care; yet, their condition as a
      survivor, with or without the long-term clinical toxicities secondary to
      treatment, will continue to affect some or all of thei

PMID- 9659947
TI  - Multiattribute approach to the assessment of health-related quality of life:
      Health Utilities Index.

PMID- 9659948
TI  - Posttraumatic distress in childhood cancer survivors and their parents.

PMID- 9659949
TI  - Transtheoretical model: applications in the prevention and treatment of cancer.
AB  - In summary, the transtheoretical model may help guide the choice of the best
      intervention approach to use when working to change behavior that is important in
      the prevention and treatment of cancer. In using this model, it is important to
      identify the person's stage of readiness for change as well as each of the other
      key constructs of the model, including confidence and temptations, perception of
      pros and cons, and use of the processes of change. Knowledge of these factors
      will guide the choice of the best stage-matched interventions to help move the
      individual forward through the stages of change to achieve long-term maintenance
      of the desired behavior.

PMID- 9659950
TI  - Attentional processes and their remediation in childhood cancer.

PMID- 9659951
TI  - The magic bullets are blanks. Purported shortcuts to improving the aging mind.

PMID- 9659952
TI  - Late-life onset of psychotic symptoms.
AB  - The authors retrospectively evaluated the etiology and clinical findings of
      patients with first manifestations of psychotic symptoms after the age of 65.
      Nearly 10% of over 1,700 consecutive geriatric patients admitted to an acute
      inpatient psychogeriatric unit had late-life onset psychotic symptoms. About
      three-fourths of these were women, usually in their seventies. Dementia of the
      Alzheimer's type was the most common cause of psychosis arising in late life,
      followed by major depression, medical/toxic causes, delirium, bipolar disorder,
      delusional disorder, schizophrenia, and schizoaffective disorder. Clinical
      manifestations consisted mostly of delusions and hallucinations.

PMID- 9659953
TI  - Incidence of asystole in electroconvulsive therapy in elderly patients.
AB  - The authors prospectively investigated the incidence of asystole (absence of
      heartbeat for 5 seconds) in elderly patients receiving electroconvulsive therapy
      (ECT) at a university-based geriatric psychiatry unit. In all, 65.8% of patients
      experienced asystole at some time during their course of ECT. Those who
      experienced asystole were significantly younger (average age, 72.2) than those
      without asystole (average age, 77.0; P = 0.026) and were also less likely to have
      cardiac rhythm disturbances on electrocardiogram (P = 0.024). Medical history,
      history of cardiac disease, electrode placement, energy level, and number of ECT
      treatments did not predict asystole. Asystole is a common side effect of ECT in
      elderly patients. It was not associated with any untoward outcome. The fact that
      "old-old" patients and those with cardiac disease are less likely to experience
      asystole than younger, healthier patients is reassuring to practitioners of ECT.

PMID- 9659954
TI  - The factor structure of the Cornell Scale for Depression in Dementia among
      probable Alzheimer's disease patients.
AB  - The authors rated 137 outpatients with probable Alzheimer's disease (AD) on the
      Cornell Scale for Depression in Dementia (CSDD) as part of routine evaluation.
      Principal-factors analysis with varimax rotation resulted in a four-factor
      solution that accounted for 43.1% of the common variance. The four factors
      included general depression (lack of reactivity to pleasant events, poor self
      esteem, pessimism, loss of interest, physical complaints, psychomotor
      retardation, sadness); rhythm disturbances (difficulty falling asleep, multiple
      night awakenings, early morning awakenings, weight loss, diurnal variation of
      mood); agitation/psychosis (agitation, mood-congruent delusions, suicide); and
      negative symptoms (appetite loss, weight loss, lack of energy, loss of interest,
      lack of reactivity to pleasant events). The observed factor structure showed
      moderate concordance with the five symptom clusters proposed in the original
      presentation of the CSDD.

PMID- 9659955
TI  - Acute neuroleptic treatment in elderly patients without dementia.
AB  - Low doses of neuroleptics are the standard for treating psychosis in elderly
      patients because of concern about inducing adverse effects. The authors found
      that fixed, low-dose neuroleptic treatment (0.15 mg/kg/day) for 10 days resulted
      in low perphenazine levels and low rates of acute response (25%) in elderly
      patients with primary psychotic illness (without dementia). Increase in initial
      dose did not speed acute response and induced adverse effects that were absent or
      minimal with low-dose treatment. With higher-dose treatment, drug blood levels
      rose disproportionately, and level-to-dose ratios were higher than those observed
      in non-elderly adults. Naturalistic follow-up suggested that response may take
      longer to develop than in non-elderly adults and that low doses for a longer
      duration may provide effective treatment.

PMID- 9659956
TI  - Depression and physical disability outcomes in depressed medically ill
      hospitalized older adults.
AB  - The authors examined depression/disability outcomes in hospitalized older medical
      patients during the year after hospital discharge to assess the pattern and rate
      of changing depression and disability, the causal relationship between these
      variables, and to identify patients at greatest risk for poor outcomes. A group
      of 119 medical patients at Duke Hospital were both depressed and disabled; they
      were followed for a median of 47 weeks after hospital discharge. Time-series
      analyses showed that depression and disability tended to track together, and most
      changes occurred within the first 6 months after discharge. Blacks were more
      likely to remit from depression despite continued disability and less likely to
      experience continued depression despite decreased disability. Patients with a
      history of depression were less likely to experience improvement in depression
      unless disability improved. Number of medical diagnoses and depression severity
      independently predicted poorer depression outcomes. Certain characteristics of
      patients during hospitalization predict depression/disability outcomes after
      discharge.

PMID- 9659957
TI  - Relationship of age, age at onset, and sex to depression in older adults.
AB  - The authors investigated the relationships among factors of age, age at onset,
      and sex in depressed older adults. A group of 96 outpatients (mean age, 60)
      diagnosed with late-(LOD) and early-onset (EOD) major depression were assessed
      for severity of depression and underwent magnetic resonance imaging (MRI). The
      MRI scans were rated for severity of white-matter hyperintensities (WMH) and
      ventricle-to-brain ratio (VBR). LOD was associated with increased amounts of WMH,
      larger VBR, and history of hypertension. Men were more severely depressed than
      women, with higher rates of neurovegetative signs and history of smoking. Age
      correlated with increased VBR and WMH, history of hypertension, history of
      percipitants for the current episode, and lack of social support. Results suggest
      that a subgroup of men may be more at risk for LOD associated with WMH and that
      sex and age at onset need to be considered in future studies.

PMID- 9659958
TI  - Divalproex treatment of mania in elderly patients.
AB  - Because lithium is difficult to use, divalproex may be an effective alternative
      for elderly manic patients. In this study, the authors retrospectively assessed
      outcome of 21 patients, age 60 to 82 years, hospitalized for a manic episode and
      treated with divalproex. The mean final divalproex dose was 1,405 mg/day, and the
      mean serum level was 72 micrograms/ml; 20 patients also received concomitant
      neuroleptic medication. Overall, 19 of the 21 patients (90%) were rated as Much
      or Very Much Improved. The only remarkable side effect, sedation, occurred in two
      patients and improved with dose reduction. Although the study suggests that
      divalproex is an effective and well tolerated treatment for elderly manic
      patients, the retrospective nature of the study and the concomitant
      administration of neuroleptic medication suggest caution in interpreting the
      findings.

PMID- 9659959
TI  - Maintenance electroconvulsive therapy for intractable Parkinson's disease.
AB  - The authors administered electroconvulsive therapy (ECT) to four patients with
      intractable Parkinson's disease who were free from depression or dementia. After
      an initial "acute" phase, subjects received bitemporal maintenance ECT every 3 to
      4 weeks for up to 12 months. Serial measures of mood, cognition, and motor
      function were performed. One subject developed cognitive impairment after seven
      maintenance treatments, and another developed delusions during the acute phase of
      the study. The two subjects completing the 12-month maintenance phase noted
      significant reductions in "off" time without impairment of cognitive functioning.

PMID- 9659960
TI  - Government investigates ongoing shortage of i.v. immune globulin.

PMID- 9659961
TI  - Recommendations for CMV treatment released.

PMID- 9659962
TI  - Increasing the use of nonprescription drugs in a group-model HMO.

PMID- 9659963
TI  - Managing C. difficile-associated diarrhea.

PMID- 9659964
TI  - Shared borders: achieving the goals of interdisciplinary patient care.
AB  - Definitions and components of interdisciplinary care, as well as means of
      implementing, reasons for adopting, and barriers to interdisciplinary care, are
      presented. A health care discipline is an area of knowledge and research that is
      critical to patient care. In multidisciplinary practice, each member of a
      clinical group practices with an awareness and tolerance of other disciplines. In
      interdisciplinary practice, members of a team actively coordinate care across
      disciplines. In an ideal interdisciplinary health care team, decisions are made
      by consensus and each discipline has an equal opportunity for input into
      decisions. To make the transition from multidisciplinary to interdisciplinary
      practice, all disciplines, rather than representing freestanding silos, must have
      shared borders that represent a common professional interest and knowledge base.
      Such a practice model will lead to an increased level of trust among professions
      and a deeper level of understanding about what each profession can contribute.
      Barriers to interdisciplinary practice include historical factors such as
      different philosophies of practice and professional training, logistics of team
      implementation, and resource limitation. To facilitate interdisciplinary
      practice, pharmacists must be competent, understand what a team is, provide
      leadership, be prepared to help develop drug therapy outcome objectives, project
      self-confidence, and demonstrate a readiness for interdisciplinary practice.
      Interdisciplinary care must be applied in a cost-effective way. Interdisciplinary
      patient care must be taught in professional schools and postgraduate training
      programs. Interdisciplinary patient care requires common values, a common vision,
      and an understanding of teamwork with the ultimate goal of serving the patient
      with wisdom.

PMID- 9659965
TI  - Clinically oriented pharmacy technicians to augment clinical services.
AB  - The justification for and the training, responsibilities, and contributions of
      two clinically oriented pharmacy technicians are described. A proposal outlining
      the clinical services being provided by pharmacists at a 650-bed medical center
      and the need for technical assistance was developed and approved. Two clinical
      technician positions were created to replace one of two eliminated pharmacist
      positions. Each of the technicians hired had worked successfully in several
      traditional pharmacy technician roles. The technicians were trained for specific
      roles and cross-trained in the basic functions of each other's roles. The
      technicians made rounds with the pharmacists to learn how to evaluate patients
      and interact with physicians and nurses and were required to demonstrate
      competence in deciding which patients required further evaluation. One technician
      focuses on providing direct clinical service support, and the other works
      primarily as a clinical administrative assistant. Half the technicians' time is
      spent performing services previously performed by pharmacists. In addition, the
      technicians track outcomes and provide clerical and data-management assistance.
      The technicians are responsible for screening and tracking approximately 400
      patients per month on well-established services and 400 per month on two new
      monitoring services. The technicians have helped develop a medication-error
      tracking program. Clinically oriented technicians freed up pharmacists' time by
      collecting routine clinical data and managing clinical projects; through protocol
      based screening and outcomes tracking, the technicians have helped to implement
      new clinical services and evaluate existing ones.

PMID- 9659966
TI  - Therapeutic-interchange program for oral histamine H2-receptor antagonists.
AB  - A therapeutic-interchange (TI) program for oral histamine H2-receptor antagonists
      at a hospital is described. In 1992 the pharmacy and therapeutics committee at a
      large teaching hospital accepted cimetidine as the preferred oral H2 antagonist.
      However, the program to promote cimetidine met with little success. The
      manufacturer of nizatidine then offered the hospital that drug at a reduced cost
      relative to all other members of the drug class. The committee recommended
      including nizatidine on the formulary; implementing a TI program so that when an
      order for an oral H2 antagonist was written nizatidine would be dispensed;
      deleting cimetidine and ranitidine tablets from the formulary; and retaining
      cimetidine and ranitidine oral liquid and i.v. formulations. The program was
      approved by the medical executive committee and was implemented in August 1994.
      Extensive efforts to inform the pharmacy, medical, and nursing staffs about the
      program were undertaken, and the pharmacy established mechanisms for monitoring
      compliance. Two months into the program, 97% of eligible patients were receiving
      nizatidine. Actual cost savings in the first four months exceeded $40,000. In
      July 1997 the same program was applied to famotidine, which had replaced
      nizatidine as the most cost-effective H2 antagonist. A successful TI program for
      oral H2 antagonists was achieved by gaining physician support for the program,
      educating providers, monitoring compliance, and responding to changes in drug
      costs.

PMID- 9659967
TI  - Stability of vancomycin in an extemporaneously compounded ophthalmic solution.
AB  - The stability of vancomycin 31 mg/mL (as the hydrochloride) in an artificial
      tears solution at -10, 4, 25, and 40 degrees C was studied. Vancomycin power was
      reconstituted with sterile water for injection to a concentration of 50 mg/mL.
      Artificial tears solution containing 0.3% hydroxypropyl methylcellulose, 0.1%
      dextran 70, 0.01% benzalkonium chloride, and 0.05% edetate disodium was used to
      produce a final concentration of 31 mg/mL. Triplicate solutions for each storage
      temperature and sampling time were prepared. The solutions were stored at -10, 4,
      25, and 40 degrees C. Samples were taken initially and at 3, 7, 10, 21, 30, 45,
      and 60 days for visual inspection and analysis by high-performance liquid
      chromatography. All solutions remained clear and colorless at -10, 4, and 25
      degrees C throughout the study period. By day 3, crystalline particles formed in
      the solutions stored at 40 degrees C. No substantial change in pH was observed at
      any time. At -10 degrees C, the solutions retained more than 90% of their initial
      vancomycin concentrations throughout the study period. The solutions retained a
      mean of at least 90% of the initial drug concentration for 21 days at 4 degrees C
      and for 7 days at 25 degrees C. For the solutions stored at 25 or 40 degrees C,
      less than 85% of the initial vancomycin concentration remained after 10 and 3
      days, respectively. Vancomycin 31 mg/mL (as the hydrochloride) in an artificial
      tears solution was stable for 45 days at -10 degrees C, 10 days at 4 degrees C,
      and 7 days at 25 degrees C in the tears solution's original container.

PMID- 9659968
TI  - Patients' knowledge of medication care plans after hospital discharge.

PMID- 9659969
TI  - ASHP guidelines on the safe use of automated medication storage and distribution
      devices. American Society of Health-System Pharmacists.

PMID- 9659970
TI  - ASHP therapeutic position statement on the preferential use of metronidazole for
      the treatment of Clostridium difficile-associated disease.
AB  - ASHP supports preferential use of oral metronidazole for treating CDAD when
      antimicrobial therapy is indicated. Oral vancomycin should be reserved for
      severe, potentially life-threatening cases or when oral metronidazole cannot be
      used. Oral metronidazole is as safe and effective as oral vancomycin and is
      considerably less costly. In addition, preliminary data suggest that routine use
      of oral vancomycin for CDAD may contribute to the spread of VRE--emerging
      nosocomial pathogens that can be extraordinarily difficult to treat. Pharmacists
      should work to foster preferential prescribing of oral metronidazole for the
      treatment of CDAD. Pharmacists should also actively seek opportunities to educate
      health care providers and counsel patients about the risks associated with the
      indiscriminate use of vancomycin and other antimicrobial agents.

PMID- 9659971
TI  - Nicotine patch needs to breathe.

PMID- 9659972
TI  - Testing commercially available folic acid capsules.

PMID- 9659973
TI  - Variation in mutation rate and direction between tetranucleotide STR loci in
      human colorectal carcinomas.
AB  - Replication error (RER) is defined as mutation events in repetitive DNA segments.
      To investigate further the RER phenomenon and reveal any differences in mutation
      outcome between different short tandem repeat (STR) loci, we have investigated
      the somatic mutation rate and the size distribution of new tumour alleles in four
      tetranucleotide STRs in a large material of unselected colorectal
      adenocarcinomas. DNA was extracted from the blood and carcinomas of 217 patients.
      All blood/tumour pairs were analysed using the STRs HUMTHO1, HUMFES/FPS,
      HUMVWA31/A and HUMF13A1. Mutations are detected at all four loci. There are
      substantial differences in mutation rate and mutation direction (i.e. expansion
      versus contraction) between different STR loci. In all four STRs, the majority of
      events represent gain or loss of a single repeat. Almost all new tumour alleles
      correspond to known alleles in a population database, indicating that these are
      also composed of integers of the four base pair repeat. There is no statistically
      significant size bias in the mutating alleles as compared to the allelic
      distribution in the population database.

PMID- 9659974
TI  - Assessment of diagnostic quantitative fluorescent multiplex polymerase chain
      reaction assays performed on single cells.
AB  - We have refined polymerase chain reaction (PCR) assays for the detection of
      sickle cell anaemia, the delta F 508 deletion causing cystic fibrosis, and the
      IVS1-110 mutation leading to beta thalassaemia, allowing them to be successfully
      performed upon single cells using fluorescent primers. We have also assessed the
      possibility of detecting aneuploidies of chromosomes 13, 18 and 21 using a
      quantitative fluorescent polymerase chain reaction (QF-PCR) with primers flanking
      polymorphic short tandem repeat (STR) markers. Trisomies were readily diagnosed
      by the detection of tri-allelic patterns. However some heterozygote normal and
      trisomic diallelic patterns did not produce the expected ratios of amplified PCR
      products due to preferential DNA sequence amplification. Total allelic drop out
      (ADO) did not occur with any of the cells tested. Multiplex QF-PCR assays can be
      performed on a single cell in under 6 h and simultaneously provide diagnosis of
      single gene defects, sex determination and an indication of selected chromosome
      aneuploidy.

PMID- 9659975
TI  - A pedigree-based linkage study of coeliac disease: failure to replicate previous
      positive findings.
AB  - Coeliac Disease (CD) is a gluten sensitive enteropathy characterised by villous
      atrophy and crypt cell hyperplasia. There is a tight HLA association between CD
      and the HLA DQ alleles DQA1*0501, DQB1*0201 (DQ2), arranged in either cis- or
      trans- configuration, are found in 98.9% of cases in Northern European
      populations and 80% in Greeks and Ashkenazi Jews resident in Israel. We have
      previously shown that the HLA alleles and CD do not co-segregate in families
      multiply affected with CD, suggesting that the HLA association is entirely due to
      the necessity to have these normal DQ alleles for CD to manifest, and that the
      main genetic predisposition lies at a locus other than the MHC. It is therefore
      possible to conduct genetic linkage studies in order to isolate the non HLA genes
      which predispose to CD. Recently a group conducted a genome screen for the non
      HLA genes in an affected sib-pair analysis and identified four non HLA loci with
      positive lod scores. We examined these loci using a pedigree based linkage study.
      Our pedigree sample consisted of a cohort of 21 families with 60 affected
      individuals and 125 unaffected family members. We used 11 microsatellite markers
      at the loci implicated and analysed the genotype data using both MLINK and MFLINK
      to detect linkage. The MLINK and MFLINK analyses did not provide any evidence to
      support the earlier findings, although the difficulties involved in analysing
      complex diseases mean that one cannot be certain that these regions do not
      harbour susceptibility loci, at least in some families.

PMID- 9659976
TI  - Spanish and African contribution to the genetic pool of the Canary islanders:
      data from GM and KM haplotypes and RFLPs in the immunoglobulin IGHG loci.
AB  - Data on the GM and KM haplotypes and RFLPs in the immunoglobulin IGHG loci are
      reported intending to evaluate the genetic contribution of the different
      populations (Europeans and Africans) who settled Tenerife Island. The GM and KM
      allotypic systems reveal an estimated European genetic admixture of 88%. The only
      possible African contribution is the presence of the GM*1,17;...;5* haplotype
      (2.5%), but no other traces of Black African characteristic haplotypes are found.
      Although new RFLP haplotypes are described, DNA variation is similar to that
      reported in Caucasoids with a marked absence of restriction fragments
      characteristic of Black Africans.

PMID- 9659977
TI  - Natural selection in industrialized countries: a study of three generations of
      Italian newborns.
AB  - We have studied the impact of natural selection on the Italian population,
      analysing the relationship between stillbirth and three related variables: birth
      weight, birth order and maternal age. A progressive relaxation of selection with
      time has been demonstrated by the reduction of the Haldane index calculated with
      respect to the three variables.

PMID- 9659978
TI  - Fine genetic mapping using haplotype analysis and the missing data problem.
AB  - The genetic basis of many human diseases, especially those with substantial
      genetic determinants, has been identified. Notable amongst others are cystic
      fibrosis, Huntington's disease and some forms of cancer. However, the detection
      of genetic factors with more modest effects such as in bipolar disorders and a
      majority of the cancers, has been more complicated. Standard linkage analysis
      procedures may not only have little power to detect such genes but they do, at
      best, only narrow the location of the disease susceptibility gene to a rather
      large region. Association studies are therefore necessary to further unveil the
      aetiological relevance of these factors to disease. However, the number of tests
      required if such procedures were used in extended genome-wide screens, is
      prohibitive and as such association studies have seen limited application, except
      in the investigation of candidate genes. In this paper, we discuss a logistic
      regression approach as a generalization of this procedure so that it can
      accommodate clusters of linked markers or candidate genes. Furthermore, we
      introduce an expectation maximization (E-M) algorithm with which to estimate
      haplotype frequencies for multiple locus systems with incomplete information on
      phase.

PMID- 9659979
TI  - Population paths implied by the mean number of pairwise nucleotide differences
      among mitochondrial DNA sequences.
AB  - Scenarios, such as populations experiencing a bottleneck or an exponential
      growth, have been suggested as candidates for explaining the observed differences
      among mitochondrial DNA sequences in a sample of a given population closed to
      migrations. Here, population size is considered as capable of varying, and the
      set of the at least 95% most probable population paths capable of producing the
      observed mean number of pairwise nucleotide differences is delineated. To do
      this, the mean and the variance of coalescence times of two genes taken in an n
      genes sample with varying population size are expressed. The observed mean
      coalescence time already echoed a set of population paths due to the variance
      associated to the coalescent process, but only specific scenarios have been
      studied, such as the bottleneck or the exponential function. However,
      mitochondrial DNA data does not reflect a single scenario, after the effect of
      the variance. These scenarios implied by pairwise nucleotide differences are
      described through a set-valued function, the 'regulation map', a convenient way
      to represent temporal population paths.

PMID- 9659980
TI  - Evaluation of a restricted likelihood ratio test for mapping quantitative trait
      loci with extreme discordant sib pairs.
AB  - Risch and Zhang recently proposed to use extreme discordant sib pairs for mapping
      quantitative trait loci. Here, it is shown that the set of genetically possible
      distributions of the number of marker alleles in such sib-pairs is described by
      two inequalities. Thus, a likelihood ratio test analogous to Holmans's possible
      triangle test for affected sib pairs can be defined. The performance of this test
      is compared to the mean test considered by Risch and Zhang. For most of the
      genetic models considered, the mean test is slightly more powerful than the
      restricted likelihood ratio test. However, for models with a rare recessive gene
      (or equivalently a common dominant gene), the restricted likelihood ratio test is
      much more powerful.

PMID- 9659981
TI  - Excitotoxic lesions of the hippocampus disrupt runway but not consummatory
      contrast.
AB  - Rats shifted from a 12-pellet to a 1-pellet reward for running in a straight
      runway showed a decrease in start, run, and goal speed to levels below rats that
      received only the 1-pellet reward throughout training (a negative contrast
      effect). Contrast was greatest in the goal region of the runway. Rats with damage
      to the hippocampus produced by the excitotoxin ibotenic acid failed to show a
      negative contrast effect under these conditions. The same lesioned rats tested in
      a consummatory, contrast procedure following a shift from 32% to 4% sucrose
      showed a negative contrast effect equivalent to sham-lesioned rats. These data
      suggest that the hippocampus is necessary for behavioral outcomes based on
      encoding or comparison that affect approach behavior, but not for such outcomes
      that affect consummatory behavior.

PMID- 9659982
TI  - CS modality transfer of two-way avoidance in rats with central and basolateral
      amygdala lesions.
AB  - Post-lesion acquisition of two-way avoidance and subsequent transfer to two
      warning signals (conditioned stimulus, CS) of different modality were
      investigated in 60 rats. In Experiment I the animals were originally trained with
      less salient (darkness) CS, then transferred to more salient compound (darkness
      and white noise), and finally to white noise CS. The opposite arrangement of the
      conditioned stimuli (CSi) during the subsequent stages was employed in Experiment
      II. In control animals, avoidance acquisition was faster and the intertrial
      responding (ITR) rate lower with the auditory than with the visual CS. Lesioned
      rats learned avoidance responses more slowly, independently of CS modality. The
      transfer to other CSi revealed dramatic between-group difference in the level and
      consistency of avoidance response, shuttle-box latencies and ITR rate. In control
      animals, transfer to more salient CSi enhanced avoidance performance, whereas
      change to less salient CS decreased it. Rather small changes in shuttle-box
      performance and consistency of avoidance response due to CS modality were seen in
      rats with the basolateral lesions. In contrast, central nucleus injury caused a
      strong deterioration in the avoidance transfer, especially when the visual CS
      followed the acoustic one. The results indicate differential involvement of the
      basolateral and central amygdala nuclei in stimulus-processing mechanisms of
      instrumental defensive behavior.

PMID- 9659983
TI  - Diurnal and gender effects by chronic portacaval shunting in rats on spontaneous
      locomotor and rearing activities in an open-field.
AB  - Behavioural disturbances in chronic experimental hepatic encephalopathy (HE) have
      been investigated for several decades, but only in recent years, the possibility
      for gender-dependent reduction of spontaneous locomotor activity has come under
      attention. Unfortunately though, the results of such gender dependency have been
      discrepant. We therefore performed an open-field behavior study in unhabituated
      female and male portacaval shunted (PCS) rats during both day- and night-time,
      monitoring locomotor as well as rearing activity for a 60 min period. The results
      revealed lower locomotor and rearing activities in both male and female PCS rats
      during night-time, compared to sham-operated controls. Daytime differences could
      only be detected in the rearing activity of female PCS versus control rats.
      Female PCS rats also spent less cumulated time rearing, compared to controls but
      no differences regarding the overall locomotor/rearing activity ratio or portion
      of the behaviours exerted in the central area of the open-field could be detected
      between PCS and controls, or between the sexes. Diurnal activity differences were
      found between control groups of both sexes but not between the female versus male
      PCS rats. Thus, our results are not supportive of any major gender-dependent
      behavioural disturbance between PCS and control rats.

PMID- 9659984
TI  - Factors shaping the response latencies of neurons in the cat's auditory cortex.
AB  - This article addresses two issues. Firstly, the hypothesis that response latency
      might be a neural code for tone frequency was examined in single-neuron data from
      the primary auditory cortex of anesthetized cats. Minimal response latencies for
      characteristic frequency (CF) tones were independent of neural CF. Mean response
      latencies for a constant amplitude CF tone were also independent of CF. These
      data, and the fact that cortical neurons do not have an obvious independent
      referent for stimulus onset time, do not support the view that latency is a code
      for frequency. Secondly, to investigate a simple threshold model of spike
      initiation time, we describe the prolongations of response latency with increases
      in stimulus rise time and their dependence on the peak amplitude of the stimulus.
      These data show that in cortical neurons, it is not the peak stimulus intensity
      which determines first-spike latency, and second, that the response latencies are
      systematically not those expected on the basis of simple threshold model.

PMID- 9659985
TI  - Specific changes in food intake elicited by blockade or activation of glutamate
      receptors in the nucleus accumbens shell.
AB  - Blockade of non-N-methyl-D-aspartic acid (NMDA) ionotropic glutamate receptors in
      the nucleus accumbens shell (AcbSh) with 6,7-dinitroquinoxaline-2,3-dione (DNQX)
      elicits intense feeding in satiated rats. In order to determine whether or not
      this feeding is part of a general behavioral activation, we observed the effect
      of intra-AcbSh DNQX injections on intake of solid food, liquid food, and water,
      and on gnawing behavior. In addition, we investigated the possibility that
      activation of a subset of these receptors with (+/-)-alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionic acid (AMPA) could suppress feeding. DNQX
      significantly increased intake of solid and liquid food, but did not
      significantly affect water intake or gnawing behavior. Furthermore, injections of
      AMPA into the AcbSh suppressed deprivation-induced feeding and intake of a
      palatable 5% sucrose solution without affecting water intake in water-deprived
      rats. Taken together, these data suggest that DNQX is acting on a system
      specifically involved with the regulation of food intake.

PMID- 9659986
TI  - Arousal mediates relations among medial paw preference, lateral paw preference,
      and spatial preference in the mouse.
AB  - Rodents exhibit two well-documented behavioural lateralities: spatial preference
      and paw preference. Waters and Denenberg [36] have identified two seemingly
      independent factors of paw preference: medial and lateral paw preference. In the
      present work, the relations among spatial preference (SP), medial paw preference
      (MPP), and lateral paw preference (LPP) during states of high and low arousal
      were examined. These preferences were measured in terms of direction, which
      describes the side of the preference regardless of strength, and degree, which
      describes the strength of the preference regardless of direction. A strong
      positive correlation between LPP and SP was found during periods of high, but not
      low, arousal. A negative correlation between the degree components of LPP and MPP
      was found during the low, but not high, arousal periods.

PMID- 9659987
TI  - Role of the medial and lateral parabrachial nucleus in acquisition and retention
      of conditioned taste aversion in rats.
AB  - When ingestion of a taste stimulus is paired with internal malaise, the animal
      remembers the taste and rejects its ingestion thereafter. This learning is
      referred to as conditioned taste aversion (CTA). To establish CTA in adult male
      Wistar rats, 0.1% saccharin and an i.p. injection of 0.15 M LiCl were used as the
      conditioned and unconditioned stimuli, respectively. To elucidate the functional
      role of the medial part of the parabrachial nucleus (PBmed) which receives taste
      information and the lateral part (PBlat) which receives general visceral
      information, confined electrolytic lesions were made to either of these regions.
      Rats with bilateral lesions of the PBlat impaired the acquisition of CTA, but
      those lesions made after the acquisition of CTA had no effect on the retention of
      this learning. The bilateral lesions of the PBmed abolished the acquisition and
      retention of CTA. The PBlat-lesioned rats showed normal taste preference
      behavior, but PBmed-lesioned rats showed impaired sensibility to taste stimuli.
      These results suggest that both the PBlat and PBmed are essential for the
      acquisition of taste aversion learning, but the PBlat is not necessary for
      retrieval of CTA.

PMID- 9659988
TI  - Glucose enhancement of 24-h memory retrieval in healthy elderly humans.
AB  - When administered soon before or after training, glucose facilitates memory in
      rodents and in several populations of humans, including healthy elderly people.
      Thus, glucose appears to enhance memory formation in a time- and dose-dependent
      manner. By assessing the effects of glucose at the time of memory tests, the
      present experiment examined the role of glucose on memory retrieval in healthy
      elderly people. On four sessions separated by a week, glucose or saccharin were
      administered immediately before hearing a narrative prose passage, as in previous
      experiments, or immediately before being tested for recall of the passage (24 h
      after training). Subjects recalled significantly more information after glucose
      ingestion than after saccharin ingestion whether the glucose was given before
      acquisition or memory tests. In addition, recall was significantly better in the
      preacquisition glucose condition relative to recall in the retrieval glucose
      condition. These findings provide evidence that glucose enhances both memory
      storage and retrieval.

PMID- 9659989
TI  - Early development of synchronized walking on the rotorod in rats. Effects of
      training and handling.
AB  - There is considerable improvement of motor coordination on the rotorod during the
      first 3 weeks of development in rats. The purpose of the present study was to
      determine some factors implicated in this improvement. From days 15-22 of age,
      rats were: (1) extensively trained on the rotorod; (2) minimally trained on the
      rotorod; (3) handled daily but not trained on the rotorod; and (4) neither
      handled nor trained. All animals were tested on the rotorod on day 23, with
      separate groups of the naive rats also being tested on days, 19, 20, 21 or 22.
      Latencies before falling and the percentage of time spent walking in time to the
      movement of the rotating rod were recorded. There was a close correspondence
      between these two scores during ontogeny. The percentage of time spent walking
      was similar among extensively trained, minimally trained, and handled rats and
      significantly higher than that measured in rats tested only on 1 day. These
      results indicate that the emergence of this postural sensorimotor skill is more
      dependent on the maturation of sensorimotor brain region than on previous
      training on the apparatus.

PMID- 9659990
TI  - Environmental enrichment results in higher levels of nerve growth factor mRNA in
      the rat visual cortex and hippocampus.
AB  - Evidence for structural modifications in the brain following environmental
      changes have been provided during the last decades. The most pronounced
      alterations following environmental manipulations have been found in the visual
      cortex. These plastic changes are supposed to reflect reorganization of neuronal
      connections involved in postnatal development and adult adjustments of
      connections involved in sensori-perceptual processing and learning. Potential
      candidates to mediate these changes are neurotrophins. Nerve growth factor (NGF)
      has been associated with cognitive functions and shown to improve the performance
      of aged rats in spatial learning and memory task. In the central nervous system,
      NGF is of importance for development and maintenance of cholinergic neurons and
      atrophy of cholinergic neurons is strongly correlated with learning and memory
      impairments. Exposure to enriched environmental conditions improves learning and
      problem-solving ability and results in plastic changes in the brain. This study
      examined the effect of environmental enrichment on expression of NGF mRNA in the
      rat visual cortex and hippocampus. Rats housed in groups in a stimulus-rich
      environment for 30 days had significantly higher levels of NGF mRNA than rats
      housed individually in single cages without stimulus-enrichment. We have recently
      presented results showing higher levels of neurotrophin-3 (NT-3) mRNA and
      improved spatial learning following environmental enrichment, and suggest that an
      interplay involving the neurotrophins NGF and NT-3 may be mediating experience
      induced structural changes.

PMID- 9659991
TI  - Early postnatal stimulation influences passive avoidance behaviour of adult rats.
AB  - In this study, the effects of stimulation on either postnatal days 1 to 7 or 21
      to 27 on the passive avoidance reaction (PAR) of 3-month-old rats were examined.
      Animals received tactile or visual stimulation or tactile-visual stimulation for
      10 min each day, and were trained at the beginning of the 4th month of life in a
      step-through apparatus using a footshock of 0.5 mA. Memory retention was measured
      24, 48, 72, 96, and 120 h after the acquisition trial. Step-through latencies to
      enter the dark compartment and the total duration of stay in the illuminated
      compartment were recorded up to 200 s. Rats that received tactile or a combined
      tactile-visual stimulation during the 1st postnatal week displayed significantly
      longer PAR latencies and a longer duration of stay in the illuminated compartment
      compared to unstimulated control animals. Visual stimulation during the postnatal
      days 1 to 7 and 21 to 27 resulted in a longer duration of stay in the illuminated
      compartment. This effect, however, was more pronounced when stimulation was
      applied during the 1st postnatal week. Rats that received tactile stimulation
      during the 4th postnatal week showed decreased PAR performance for all measured
      parameters when compared to animals that received stimulation during the 1st
      postnatal week. Furthermore, combined tactile-visual stimulation during the 4th
      postnatal week led to a reduced duration of stay in the illuminated compartment
      when compared to the stimulation during the 1st postnatal week. These findings
      can be attributed to the higher degree of plasticity and to a heightened
      sensitivity to various stimuli in the 1st postnatal week. The results suggest
      that tactile, visual or combined tactile-visual stimulation have a long-lasting
      effect on the ability of adult rats to cope with stressful tasks.

PMID- 9659992
TI  - Lesions of the primate rhinal cortex cause deficits in flavour-visual associative
      memory.
AB  - Three Cynomolgus monkeys (Macaca fascicularis) learned a flavour-visual
      conditional discrimination problem, in which one of two possible food items was
      presented at the beginning of each trial, and acted as an instruction cue to
      signal which of two visually distinct stimulus objects the animal must displace
      on that trial in order to obtain a further food reward. The task was learned
      first in light then in dark conditions. Following rhinal cortex ablation the
      animals were unable to use the flavour properties of the food items to guide
      visual choices, performing at close to chance levels. Postoperative performance
      on a food preference test showed that their problem in associating a flavour cue
      with a visual object in the conditional learning task also extended to aberrant
      choice of foods based on their visual appearance.

PMID- 9659993
TI  - Differential site-specific effects of parafascicular stimulation on active
      avoidance in rats.
AB  - To study the effects of parafascicular intracranial electrical stimulation (PF
      ICS) on two-way active avoidance acquisition (five training sessions of ten
      trials each, one session per day) and long-term retention (one session of ten
      trials), two experiments were carried out. Experiment I tested if posttraining PF
      ICS can differentially affect the conditioning, depending on the stimulated
      region of the nucleus. Results indicated that rats stimulated at the posterior
      region of the parafascicular nucleus (PF) showed a better acquisition than those
      stimulated at the central one. Experiment II evaluated the effects of the
      stimulation at the medial, lateral and posterior parts of the PF area on the same
      task. Results showed that medial and lateral PF ICS disrupted two-way active
      avoidance, and that posterior PF ICS enhanced the long-term retention of the
      conditioning. These results suggest a possible role of the PF in modulatory
      processes of learning and memory, confirming that this nucleus is functionally
      heterogeneous. Potential facilitative effects are discussed in terms of the
      relations of the PF to the arousal system and the subparafascicular thalamic
      nucleus. Disruptive effects are discussed based on the relations of the PF with
      the 'motor' and 'associative-limbic' basal ganglia circuits.

PMID- 9659994
TI  - Modification of behavioral responses induced by electrical stimulation of the
      ventral tegmental area in rats.
AB  - To investigate the role of the ventral tegmental area (VTA), a source of the
      mesolimbic dopaminergic pathway, in paranoid psychosis, a detailed analysis of
      the behavioral responses induced by electrical stimulation of the VTA was made.
      Abnormal behavior induced by bilateral high-frequency stimulation of the VTA
      consisted of two components: forward locomotion and exploration. Similar
      responses were obtained when the nucleus accumbens (NAC) or prefrontal cortex
      (PFC) were stimulated. The expression of behavioral responses to stimulation was
      significantly attenuated by dopamine (DA) receptor or antagonists, such as
      haloperidol, YM-09151-2 and SCH23390. These results indicate that VTA stimulation
      causes a transient hyperdopaminergic state in the brain, that resembles
      psychostimulant-induced abnormal behavior. The effects of chronic administration
      of methamphetamine (MAP) on the behavioral responses to electrical stimulation of
      the VAT were also investigated. Although an acute administration of MAP did not
      affect the behavioral responses to electrical stimulation of the VTA, chronic
      treatment with MAP (for 2 weeks) caused a long-lasting reduction in the
      electrical threshold for the induction of abnormal behavior, compared with
      chronic saline-treated rats. It is suggested that a lasting enhancement in the
      behavioral response to stimulation of VTA neurons may contribute to the etiology
      of paranoid schizophrenia and amphetamine psychosis.

PMID- 9659995
TI  - Kinematic analysis of prehension movements in children.
AB  - The kinematics of the reach-to-grasp movement were analyzed in ten healthy
      children (age 6-7 years) under different experimental conditions: distance and
      size of the target objects, and visual feedback during the reach were varied in a
      within-subjects design. To assess age-related differences, the same experiments
      were performed in ten healthy adults. The experimental set-up was scaled
      according to body proportions to obtain equivalent conditions for both age
      groups. The temporal coupling between the transport and grasp components of
      prehension was very similar in children and adults. Peak transport velocity
      increased by the same factor in both age groups when the object distance was
      doubled. However, the decelerating approach phase was shorter in the children,
      who opened their hands relatively wider than adults. Unlike the adults, children
      failed to scale their grip aperture according to object size when visual feedback
      during the movement was lacking. The grip aperture increased with object distance
      in adults, but not in the children. The intrasubject variability of kinematic
      parameters was distinctly higher in the children. The results suggest that grip
      formation is not yet mature at an age of 6-7 years, depending more on visual
      feedback than in adult prehension.

PMID- 9659996
TI  - Mild traumatic lesion of the right parietal cortex of the rat: selective
      behavioural deficits in the absence of neurological impairment.
AB  - Fluid impact models are widely used to study the histological and neurochemical
      consequences of traumatic brain injury and although behavioural consequences have
      also been studied, behavioural changes are often confounded by non-specific
      neurological deficits. In the present study we investigated behavioural effects
      of a unilateral mild traumatic lesion of the right lateral parietal cortex. This
      region is implicated in a number of basic and complex behaviors, and we therefore
      analyzed the performance of rats in a diverse range of behavioural procedures.
      The lesion had no effects on general neurological function, motor activity
      (activity boxes, rota-rod and paw reaching tests), habituation to a novel
      environment (holeboard), spatial learning ability (Morris water maze) or anxiety
      (elevated plus-maze). However, the lesioned animals demonstrated lower levels of
      exploration than the control group when novel objects were placed beneath some of
      the holes in the holeboard. Lesioned animals also differed from controls in their
      performance in passive and active avoidance procedures. In a step-through passive
      avoidance test the lesioned rats performed worse than the sham-operated controls,
      i.e. they had significantly lower entry latencies on the 2nd day. In contrast, in
      the active avoidance task the lesioned animals performed better than sham
      operated rats, demonstrating a better ability to learn to avoid and escape from
      the shock. These diverse results in different tests of learning and memory, in
      particular the impairment in passive avoidance and the improvement in active
      avoidance behavior, are difficult to reconcile with a simple effect of the lesion
      on cognitive performance per se. The complete absence of general neurological
      deficits following the mild traumatic injury rules out the possibility that the
      observed behavioural changes reflect a non-specific impairment. These results
      demonstrate that mild traumatic lesion of the right parietal cortex can induce
      relatively selective behavioural changes that may serve to study functional
      recovery after trauma. However further work is required to establish the
      underlying deficit(s) that has led to the behavioural effects described here.

PMID- 9659997
TI  - Mild traumatic lesion of the right parietal cortex in the rat: characterisation
      of a conditioned freezing deficit and its reversal by dizocilpine.
AB  - We have previously demonstrated that traumatic injury of the lateral aspect of
      the right parietal cortex results in reduced acquisition of the passive avoidance
      task but enhanced learning in an active avoidance procedure. In order to try to
      explain the apparent dichotomy between these findings a series of experiments
      examined the effect of fluid percussion-induced traumatic brain injury (FP-TBI)
      on the conditioned freezing response to a context previously paired with an
      aversive stimulus. Rats subjected to FP-TBI displayed less conditioned freezing
      than the sham-operated controls. This effect was particularly marked when the
      delay between context exposure and footshock was short (< or = 30 s) and was no
      longer significant when this delay was 3 min, indicating that the injured animals
      did not have an impaired freezing response per se. This phenomenon was enduring
      such that it could still be observed 2 months following the surgery. There was no
      significant freezing deficit after FP-TBI of the motor cortex, demonstrating that
      the site of injury is important and that the freezing deficit is not a general
      response to CNS trauma. The NMDA receptor antagonist dizocilpine (MK-801, 1 mg/kg
      i.v.) significantly reduced the trauma-induced freezing deficit when administered
      as a single bolus 15 min prior to the surgery, or as three repeated treatments (3
      x 0.33 mg/kg) 15 min, and 6 and 24 h following lesion. The trauma-induced deficit
      in conditioned freezing can explain the differences in active and passive
      avoidance behaviours and appears to be specific to lesion of the lateral parietal
      cortex. In addition, the behavioural deficit can be attenuated using the
      neuroprotective agent dizocilpine, suggesting that it may prove useful as a
      sensitive and specific measure of cortical damage following traumatic injury.

PMID- 9659998
TI  - Paw and limb use in skilled and spontaneous reaching after pyramidal tract, red
      nucleus and combined lesions in the rat: behavioral and anatomical dissociations.
AB  - The pyramidal tract and red nucleus send prominent projections to the spinal cord
      and are thought to co-operate in producing skilled movements. In the present
      study, skilled reaching for food located on a shelf and spontaneous grasping,
      handling and eating pieces of pasta were video-recorded and analyzed in control
      rats, rats with unilateral ibotenic acid lesions of the red nucleus (RN),
      unilateral pyramidal tract lesions (PT) and combined lesions. The behavioral
      results suggest that skilled movements are organized as action patterns, easily
      recognizable and distinctive for each task. In both skilled and spontaneous
      reaching, PT lesions reduced success more than RN lesions, suggesting a greater
      role for the PT in guiding limb movements. Both lesions impaired rotatory
      movements including limb aiming, pronation and supination. RN lesions
      additionally abolished the arpeggio movement by which the paw is oriented for
      searching and grasping. Combined lesions were additive as rats lost both rotatory
      movements and arpeggio. Nevertheless, even after combined lesions, the rats were
      able to advance the limb, grasp food and withdraw the limb. The sparing following
      combined lesions suggests that other neural systems as well as compensatory
      adjustments assist the impaired limb. The results are discussed in relation to
      the possible distinctive contributions of the rubrospinal and corticospinal tract
      to the action patterns that comprise skilled movements in rats.

PMID- 9659999
TI  - A characterization of performance by men and women in a virtual Morris water
      task: a large and reliable sex difference.
AB  - In many mammalian species, it is known that males and females differ in place
      learning ability. The performance by men and women is commonly reported to also
      differ, despite a large amount of variability and ambiguity in measuring spatial
      abilities. In the non-human literature, the gold standard for measuring place
      learning ability in mammals is the Morris water task. This task requires subjects
      to use the spatial arrangement of cues outside of a circular pool to swim to a
      hidden goal platform located in a fixed location. We used a computerized version
      of the Morris water task to assess whether this task will generalize into the
      human domain and to examine whether sex differences exist in this domain of
      topographical learning and memory. Across three separate experiments, varying in
      attempts to maximize spatial performance, we consistently found males navigate to
      the hidden platform better than females across a variety of measures. The effect
      sizes of these differences are some of the largest ever reported and are robust
      and replicable across experiments. These results are the first to demonstrate the
      effectiveness and utility of the virtual Morris water task for humans and show a
      robust sex difference in virtual place learning.

PMID- 9660000
TI  - Caveat emptor.

PMID- 9660001
TI  - Update in oculoplastic surgery: lacrimal problems.

PMID- 9660002
TI  - Update in cataract and refractive surgery.

PMID- 9660003
TI  - Scanning electron microscopic examination of porous orbital implants.
AB  - OBJECTIVE: To compare the structural makeup of five porous orbital implants: two
      made of coralline hydroxyapatite (Bio-Eye and Chinese implant), one of synthetic
      hydroxyapatite (FCI), one of porous polyethylene (Medpor) and one of alumina. The
      Bio-Eye, Medpor and alumina implants are currently available in Canada. OUTCOME
      MEASURES: Pore size, pore interconnectivity and microcrystalline architecture.
      RESULTS: The Bio-Eye had multiple interconnected pores ranging from 300 microns
      to 700 microns in width; higher-power views showed coarse-appearing crystals
      approximately 2 microns wide. The FCI implant showed similar interconnectivity of
      the pores but fewer pores, which were about 300 microns to 500 microns in size.
      Higher-power views showed hexagonal crystals about 1 micron to 5 microns in size.
      The Chinese hydroxyapatite implant had multiple interconnected pores ranging from
      200 microns to 700 microns in size. The crystals were similar in appearance to
      those of the Bio-Eye but were smaller and more granular. The 150-micron pore size
      Medpor implant had irregularly shaped pores ranging from 100 microns to 500
      microns in size. The 400-micron pore size implant had pores that looked more like
      channels that coalesced; the pores and channels ranged in size from 125 microns
      to 1000 microns. In both cases higher-power views showed a woven texture. In the
      alumina implant the pores were well connected and evenly distributed and were
      approximately 500 microns in size. On high-power studies the implant showed a
      cobblestone-like pattern of crystals approximately 4 microns to 5 microns wide.
      CONCLUSIONS: There are notable differences in pore size, pore interconnectivity
      and microcrystalline architecture between the implants studied. These features
      may be important in the overall biocompatibility of the implant.

PMID- 9660004
TI  - An epidemiologic investigation of unexpected refractive errors following cataract
      surgery.
AB  - OBJECTIVE: To determine the extent and magnitude of unexpected refractive errors
      following cataract surgery with intraocular lens (IOL) implantation and to
      determine what characteristics were associated with the errors. DESIGN: In this
      nonconcurrent prospective study, preoperative, intraoperative and postoperative
      information was collected from the charts of the 523 consecutive patients who
      underwent cataract extraction and polymethylmethacrylate IOL implantation
      performed by one of nine participating surgeons between Jan. 1 and Apr. 30, 1995,
      or the same dates in 1996. SETTING: University-affiliated eye care centre in
      Vancouver. OUTCOME MEASURE: Postoperative excess correction, calculated for each
      patient by subtracting the actual postoperative spherical equivalent from the
      expected spherical equivalent. Eyes with an excess correction of more than 1.00
      dioptre were considered "overcorrected." RESULTS: Univariate analysis showed that
      the formula used to calculate the lens power, axial length, year of surgery, A
      constant/surgeon factor used and lens manufacturer were associated with
      overcorrection. In a logistic regression model, lens manufacturer was the only
      variable independently associated with overcorrection. CONCLUSIONS: Routine
      reporting and follow-up is necessary to identify this kind of "outbreak" and the
      associated factors. The current guidelines of the Health Protection Branch,
      Health Canada, for evaluation of IOLs that have changed manufacturers are not
      adequate to identify the kind of error that we detected.

PMID- 9660005
TI  - Bilateral amaurosis following peribulbar anesthesia.

PMID- 9660006
TI  - Air gun injury presenting as axial proptosis.

PMID- 9660007
TI  - Respiratory arrest following peribulbar anesthesia for cataract surgery: case
      report and review of the literature.

PMID- 9660008
TI  - Bilateral serous retinal detachments associated with Goodpasture's syndrome.

PMID- 9660009
TI  - Outcome criteria in strabismus surgery.
AB  - Criteria for success in strabismus surgery should include more than just the
      alignment result in primary position. It is important to consider as well the
      extent of the field of BSV gained: restoring a useful range of BSV will maximize
      the patient's ability to carry on daily activities. Psychometric tests can also
      be used to provide objective measures of improvement following strabismus
      surgery. Irrespective of the patient's age, the realigning of an eye is
      reconstructive, not cosmetic, surgery. Surgery in children and adults can restore
      fusion and normalize the field of BSV in most cases. These gains are possible
      even in the presence of amblyopia. It could be argued that realigning a blind eye
      yields no functional improvement and should not necessarily be covered by
      insurance plans. These cases are not common. In all other cases the functional
      benefits of adult strabismus surgery justify maintaining insurance coverage for
      this surgery in jurisdictions throughout North America.

PMID- 9660010
TI  - The "Mozart effect" on epileptiform activity.
AB  - The "Mozart Effect," using the Piano Sonata in D Major (K.448), was examined in
      patients with seizures. In 23 of 29 instances significant decreases in
      epileptiform activity were noted from patients even in coma, with status
      epilepticus or with periodic lateralized epileptiform discharges (PLEDs). The
      effect may be immediate or require 40-300 sec to manifest itself. The change in
      the amount of ictal activity in one patient in coma was from 62% before the music
      to 21% during Mozart. Amplitudes of these discharges also have often decreased.
      Examples of PLEDs on both temporal areas are shown in which the effect was only
      on the left temporal area but in other patients only on the right temporal area.
      Brain maps during the music showed theta and alpha activity decreased on the
      central areas, while delta waves increased on the frontal midline area. The basis
      of this effect is likely that the superorganization of the cerebral cortex with
      its highly structured radial columns seen throughout both hemispheres may
      resonate with the superior architecture of Mozart's music.

PMID- 9660011
TI  - Reversible hypercalcemic cerebral vasoconstriction with seizures and blindness: a
      paradigm for eclampsia?
AB  - Although hypercalcemia may cause drowsiness, lethargy, weakness, confusion and
      coma it rarely causes seizures or cerebral infarction. The patient presented had
      a clinical evolution from hallucinosis to a generalized tonic-clonic seizure, and
      subsequent cortical blindness with occipital cerebral ischemia as evidenced by
      SPECT and MRI scans. EEG revealed occipital PLEDs. With reversal of
      hypercalcemia, there was a return of vision, resolution of EEG epileptiform
      activity, although with some residual occipital infarction. This case, in concert
      with a literature review of hypercalcemia, reveals examples of occipital and
      watershed ischemia, blindness, seizures and hypertension, a pattern markedly
      similar to that of eclampsia. Furthermore, medications such as magnesium sulfate,
      believed to reverse cerebrovasospasm responsible for the eclamptic neurologic
      findings, may counter the effects of hypercalcemia at a cellular level, lending
      support to a calcium-mediated injury in eclampsia.

PMID- 9660012
TI  - Correlation between contingent negative variation and regional cerebral blood
      flow.
AB  - The relationship between contingent negative variation (CNV) and regional
      cerebral blood flow was investigated, using the stable xenon computed tomography
      method. Seventeen cases of chronic multiple cerebral infarction in the
      perforating artery areas (vascular dementia, mean age 67.0), 6 cases of
      Alzheimer's disease (mean age 69.5) and 8 healthy controls (mean age 62.5) were
      studied. Regional cerebral blood flows in the frontal, temporal, parietal and
      occipital cortex, frontal, temporal and occipital white matter, caudate nucleus,
      putamen and thalamus were measured. The amplitude of early CNV was significantly
      smaller in the vascular dementia group than in the healthy control group. The
      blood flows in the parietal cortex and thalamus were significantly lower in the
      vascular dementia group than in the healthy control group. There was a
      significant positive correlation between the amplitude of early CNV and frontal
      cortex blood flow. No significant correlations were present between the CNV and
      the other regional cerebral blood flows nor in healthy controls. The amplitude of
      CNV has been reported to be decreased in dementia. From the present study, the
      amplitude of early CNV was considered to be influenced by the blood flow in the
      frontal cortex.

PMID- 9660013
TI  - EEG abnormalities in systemic lupus erythematosus.
AB  - The medical records of 478 SLE patients were reviewed. Ninety-five patients
      (19.9%) with a history of seizures were identified. EEG reports were available on
      62. EEGs were interpreted as normal in 8 (12.9%) and abnormal in 54 (87.1%).
      Abnormal EEGs were reviewed for the presence of unilateral and bilateral
      abnormalities. Left hemisphere abnormalities were identified in 43 (79.6%), right
      hemisphere abnormalities in 4 (7.4%), and bilateral abnormalities in 7 (13.0%)
      patients with SLE. Abnormalities included theta and delta slowing and sharp wave
      activity. In 32 of the 43 (74.4%) patients with left hemisphere abnormalities,
      the abnormalities were localized to the left temporal leads. These findings
      suggest selective damage to the left temporolimbic region in patients with SLE.

PMID- 9660014
TI  - Topographical EEG analysis of rolandic spikes.
AB  - We performed topographic EEG investigation with instant voltage mapping in 57
      patients with a Rolandic spike focus including 35 patients with benign Rolandic
      epilepsy. A pronounced maximal negativity of "Rolandic" spikes could be
      demonstrated over central or mid-temporal electrodes, with a spread to parietal
      or upper frontal areas with a dipole formation (centrotemporal negativity,
      frontal positivity) and involvement of midline. There was a moderate correlation
      between spike amplitude or duration with spread to adjacent areas. No other focal
      abnormalities such as focal slowing could be revealed by visual or FFT EEG
      analysis. During light sleep spike activity was pronounced and often associated
      with generalized spike wave activity. Thus, a functional disturbance rather than
      a structural lesion can be assumed.

PMID- 9660015
TI  - Intermittent rhythmic delta activity (IRDA) in a patient with band heterotopia.
AB  - We report a patient with band heterotopia whose electroencephalogram (EEG) showed
      typical morphological features of intermittent rhythmic delta activity (IRDA).
      This 18-year-old woman had complex partial seizures. Neuropsychometry revealed
      mental dysfunction. Magnetic resonance imaging (MRI) showed bilaterally
      symmetrical layer of heterotopic gray matter in deep white matter over the
      frontal, parietal and occipital regions. This case is the first report of IRDA
      detected in band heterotopia.

PMID- 9660016
TI  - Triphasic waves associated with acute naproxen overdose: a case report.
AB  - Triphasic waves (TWs) can be recorded on EEG in the course of several metabolic
      disorders, mainly hepatic encephalopathy. A case of acute encephalopathy due to
      naproxen intoxication is reported, in the course of which diffuse, bilateral and
      symmetrical TWs were recorded. Biochemical mechanisms that might determine both a
      complex encephalopathy and TWs are discussed.

PMID- 9660017
TI  - ERPs of characters of Chinese words compared with tone and picture stimuli in
      adolescents and aged persons.
AB  - ERPs to target stimulation with tone, picture and characters of Chinese words
      ([symbol: see text] CCW were target stimulus) were studied in adolescents group
      and aged persons group. The age of the adolescent group ranged from 15-17 years,
      with 30 males and 30 females; the age of the elderly persons group ranged from 60
      79 years with 29 males and 18 females. The latencies of N2 of aged persons in
      tone stimulus and in picture stimulus among males were longer than those of
      adolescents. The latencies of P3 and RT of aged persons were longer than those of
      adolescents in three stimulus models. The gender differences of latencies of N2
      and RT were not obvious in two groups, but were apparent in P3 in adolescents.
      The latencies of N2, P3 and RT of CCW stimulus were longer compared to those of
      picture stimulus in the adolescent group, but not in the aged persons group.

PMID- 9660018
TI  - Women 35 years of age or younger have higher locoregional relapse rates after
      undergoing breast conservation therapy.
AB  - BACKGROUND: The use of breast conservation therapy (BCT) in young women with
      invasive breast cancer is controversial. To examine this important issue, rates
      of locoregional recurrence and overall survival after BCT were compared in two
      subsets of women--those < or = 35 years of age at time of surgery and their older
      counterparts. STUDY DESIGN: We examined records of 290 women with invasive breast
      cancer treated with BCT (local excision and axillary dissection) at Memorial
      Sloan-Kettering Cancer Center between 1984 and 1993. These included 87 patients <
      or = 35 years of age at time of surgery and 203 randomly selected patients > 35
      years of age. Followup was obtained from physician charts or patient interviews,
      or both. Complete data on clinicopathologic factors, recurrence, and survival
      were available on 280 patients. RESULTS: Median followup from time of operation
      was 8.0 years for the entire group. Mean tumor size was 2.0 cm for women < or =
      35 years and 1.8 cm for those > 35 (p = 0.07). Involved nodes were found in 48%
      of the young patients and 36% of the older patients (p = 0.08). Within our study
      group (n = 280), 274 patients received radiotherapy. Women < or = 35 years of age
      had significantly higher rates of locoregional recurrence and lower rates of
      overall survival than their older counterparts (p < 0.05). On multivariate
      analysis, these results were independent of tumor size and nodal status. A
      history of locoregional relapse, however, was not associated with a higher rate
      of death from disease in the entire cohort or in either age group. CONCLUSIONS:
      Patients < or = 35 years of age undergoing BCT for invasive breast cancer are at
      higher risk for locoregional recurrence and death from disease. The higher
      mortality rate, however, does not appear to be a direct result of locoregional
      relapse. Additional study is required to verify these findings. Currently, young
      age does not exclude patients from BCT in our practice. But, we include this data
      as part of the informed consent process.

PMID- 9660019
TI  - Detection of occult breast cancer micrometastases in axillary lymph nodes using a
      multimarker reverse transcriptase-polymerase chain reaction panel.
AB  - BACKGROUND: Axillary lymph node status in breast cancer patients remains the
      single most important predictor of outcomes. Current methods of histopathologic
      analysis may be inadequate because 30% of node-negative patients recur. The
      purpose of this study was to test the hypothesis that a multigene reverse
      transcriptase-polymerase chain reaction (RT-PCR) panel provides a more sensitive
      method to detect axillary lymph node metastases than routine pathologic
      examination. STUDY DESIGN: Sixty-one consecutive breast cancer patients were
      evaluated, with nine normal control patients. Nodes > 1 cm were bisected for
      histopathologic and RT-PCR analysis. Nodal tissue was homogenized, and total RNA
      was converted into cDNA with reverse transcriptase. Reverse transcriptase
      polymerase chain reaction analysis was performed with primers specific for
      keratin-19, c-myc, prolactin inducible protein (PIP), and beta-actin using
      ethidium bromide gel electrophoresis. Reverse transcriptase-polymerase chain
      reaction positive/ pathology negative axillary lymph nodes were reevaluated using
      step sectioning and immunohistochemical staining. RESULTS: Thirty-seven patients
      had pathologically negative axillary lymph nodes, of which 15 (40%) were positive
      by RT-PCR analysis. Two RT-PCR negative results (one probably from tissue
      processing error and the other secondary to sampling error) among the 24
      histologically positive specimens were detected (8%). The number of patients in
      each pathologic stage was 26 patients in stage I; 18, stage IIA; 7, stage IIB; 7,
      stage IIIA; 3, stage IIIB; and 0 patients in stage IV. By RT-PCR staging, 8 of 26
      patients went from stage I to IIA (30%), and 7 of 18 from stage IIA to IIB (39%).
      Of the RT-PCR positive individuals who were stage I by pathologic analysis, 100%
      were found to be c-myc positive, 0% keratin-19 positive, and 0% PIP positive; for
      stage IIIB patients these markers were 50%, 100%, and 100% respectively.
      Additionally, an increasing number of positive markers per specimen appeared to
      correlate with larger primary tumor size (p < 0.01) and decreased predicted 5
      year survival (r = 0.950, p < 0.002). CONCLUSIONS: Multimarker RT-PCR analysis
      appears to be a readily available and highly sensitive method for the detection
      of axillary lymph node micrometastases. Longterm followup of RT-PCR positive
      patients will be required to determine its clinical relevance. If validated as a
      predictor of disease recurrence, this method would provide a powerful complement
      to routine histopathologic analysis of axillary lymph nodes.

PMID- 9660020
TI  - Immediate reconstruction after complete skin-sparing mastectomy with autologous
      tissue.
AB  - BACKGROUND: Immediate breast reconstruction with autologous tissue can re-create
      a breast mound that closely resembles the native breast in shape and consistency.
      Results are limited by scarring and color differences between flap and native
      breast skin. This study reviews all patients undergoing complete skin-sparing
      mastectomy with immediate autologous tissue reconstruction over the past 4 years.
      STUDY DESIGN: Twenty-eight patients with a mean age of 43 years (range, 32-53
      years) were retrospectively reviewed. Requirements for the complete skin-sparing
      approach included a favorable biopsy scar location, adequate areolar diameter,
      and suitable donor site for autologous tissue reconstruction. Ninety-two percent
      of patients were reconstructed with a transverse rectus abdominis
      musculocutaneous flap. RESULTS: There were no instances of flap loss or local
      recurrence during the followup period (mean, 27 months; range, 14-48 months).
      Complications at the reconstruction site were minor and limited to cellulitis,
      periareolar skin loss, and the need for repeat skin excision because of a very
      close pathologic margin. Donor site complications were seen in five patients.
      Aesthetic results were judged as excellent or good in 75% of patients.
      CONCLUSIONS: Complete skin-sparing mastectomy with immediate autologous tissue
      reconstruction has enhanced immediate breast reconstruction by reducing scar
      burden and eliminating color differences without an increased incidence of local
      recurrence. This procedure is limited by appropriate patient selection and
      technical expertise in performing the mastectomy.

PMID- 9660021
TI  - Dual blockade of P-selectin and beta2-integrin in the liver inflammatory response
      after uncontrolled hemorrhagic shock.
AB  - BACKGROUND: Neutrophil infiltration is a characteristic feature of the hepatic
      injury associated with prolonged hypotension. Previous work has already stressed
      the important contribution of neutrophil-endothelial cell interactions in the
      organ injury seen after hemorrhagic shock. Single-blockade strategies using
      monoclonal antibodies (MAbs) against either selectin or integrin receptors have
      been demonstrated to be effective in limiting the tissue inflammatory response
      observed in this clinical disorder. One unexplored topic is the additive
      effect(s) and the potential antiinflammatory properties of the combined blocking
      of P-selectin plus beta2-integrin in the liver inflammatory response after
      uncontrolled hemorrhagic shock in rats. STUDY DESIGN: Sprague-Dawley rats (n =
      64) weighing 250-300 g were included in a three-phase model of uncontrolled
      hemorrhagic shock. A prehospital phase consisted of 90 minutes of fluid
      resuscitation with lactated Ringer's solution to reach a mean arterial pressure
      (MAP) of 40 mmHg; a hospital phase consisted of 60 minutes of hemostasis and
      fluid resuscitation with lactated Ringer's solution to reach a MAP of 80 mmHg;
      and the third phase was 3 days of observation. All rats had 3 mL/100 g of blood
      volume shed during the initial 15 minutes. At 30 minutes, 75% tail amputation
      produced uncontrolled hemorrhagic shock. Four groups were randomized (n = 16 per
      group), and treatment at the beginning of resuscitation included normal saline
      (group 1); anti-P-selectin MAb, RMP-1 (group 2); anti-beta2-integrin MAb, WT.3
      (group 3); or anti-P-selectin plus anti-beta2-integrin MAbs (group 4). The
      following indices were evaluated: fluid requirements for resuscitation, liver
      injury tests, liver tissue myeloperoxidase, and liver histology. RESULTS: Dual
      blockade of P-selectin and beta2-integrin significantly reduced fluid
      requirements for resuscitation (p < 0.05). We also observed a statistically
      significant improvement (p < 0.05) in tests demonstrating hepatic injury,
      myeloperoxidase in hepatic tissue, and histology studies. Survival was increased
      from 40% in controls to 60% with the dual-blockade treatment. CONCLUSIONS: These
      results indicate that dual-blockade strategies aimed at P-selectin and beta
      integrin provided a protective effect in the liver inflammatory response after
      uncontrolled hemorrhagic shock in rats. Although dual blockade was more effective
      than either individual blockade alone, questions remain about the possible
      redundancy in the inflammatory adhesion pathways after this clinical condition.

PMID- 9660022
TI  - Effects of hyperventilation and hypoventilation on PaCO2 and intracranial
      pressure during acute elevations of intraabdominal pressure with CO2
      pneumoperitoneum: large animal observations.
AB  - BACKGROUND: The side effects of acute elevations in intraabdominal pressure (IAP)
      are related to a multifactorial etiology. Previous studies have reported that
      acute elevations in IAP produce an immediate increase in intracranial pressure
      (ICP). This study was designed to analyze the reasons for increased ICP during
      acute elevations of IAP and to determine the combined effects of IAP and changes
      in ventilation indices on ICP and hemodynamic indices. STUDY DESIGN: Five pigs
      were studied. A subarachnoid screw was placed for ICP monitoring. The jugular
      vein, femoral vein, and femoral artery were cannulated. Mean arterial pressure
      (MAP), central venous pressure (CVP), ICP, and arterial pressure of carbon
      dioxide (PaCO2) were monitored before and after carbon dioxide pneumoperitoneum
      was established at 0, 10, and 20 mmHg of IAP Effects of hyperventilation and
      hypoventilation were recorded and compared with baseline ventilation. Cavography
      was performed to evaluate the morphology of the inferior vena cava (IVC) at
      different levels of IAP. Multiple regression and Student's t-test were used to
      examine the effects of IAP and ventilation on dependent variables. RESULTS: The
      IVC showed a progressive narrowing at the level of the diaphragm as IAP was
      increased. There was a simultaneous increase in CVP, MAP, and ICP. The mean
      changes in ICP with hypoventilation were significantly larger than with
      hyperventilation. CONCLUSIONS: Acutely increased IAP displaces the diaphragm
      cranially, narrowing the IVC and increasing intrathoracic pressure. This
      increases CVP and increases ICP by venous stasis and increased pressure in the
      sagittal sinus with decreased resorption of cerebrospinal fluid. Hemodynamic
      changes are directly related to the rise in ICP. Hypoventilation and hypercarbia
      significantly increase ICP when compared with hyperventilation and hypocarbia.
      Hyperventilation does not significantly decrease ICP during acute elevations of
      IAP.

PMID- 9660023
TI  - Combined posterior and transaxillary approach for neurogenic thoracic outlet
      syndrome.
AB  - BACKGROUND: Incomplete removal of the first rib in operations intended to
      decompress the thoracic outlet is often seen after the single transaxillary
      approach (often leaving a posterior stump) or supraclavicular techniques (leaving
      an anterior stump). The former may also cause neurogenic and vascular injuries
      because the exposure is often poor in attempting complete removal of the first
      rib posteriorly and the surgeon faces a significant struggle. STUDY DESIGN: A new
      operative procedure is described entailing two stages using two separate
      incisions: a transaxillary and posterior incision done at the same sitting that
      accomplishes complete removal of the first rib with less risk. This combined
      approach is done with the help of a new arm holder device during the
      transaxillary stage followed by a small incision behind the trapezius ridge for
      posterior access to the rib. RESULTS: I present 33 patients in whom this
      operation was implemented, with a cure rate of 79%, improvement in 15%, and
      unchanged in 6%, with no complications or mortality. Technical details are
      presented. CONCLUSIONS: A double-incision approach is recommended as a safer and
      more effective method to accomplish complete removal of the first rib than are
      single transaxillary supraclavicular techniques in cases with thoracic outlet
      obstruction.

PMID- 9660024
TI  - A prospective, randomized trial comparing laparoscopic versus conventional
      techniques in colorectal cancer surgery: a preliminary report.
AB  - BACKGROUND: Uncontrolled studies using laparoscopic techniques in colorectal
      surgery have not demonstrated clear advantages to these procedures compared with
      conventional ones, and surgeons are concerned about unusual early recurrences
      reported after laparoscopic colorectal cancer surgery. STUDY DESIGN: We conducted
      a prospective, randomized trial in one surgical department comparing laparoscopic
      (LAP) and conventional (CON) techniques in 109 patients undergoing bowel
      resection for colorectal cancers or polyps. Postoperatively, all patients
      underwent measurement of pulmonary function tests every 12 hours, and were
      treated identically on a highly controlled protocol with regard to analgesic
      administration, feeding, and postoperative care. RESULTS: Of the 55 patients
      assigned to LAP and 54 to the CON group, there were 42 and 38 with cancer,
      respectively (the other patients had large adenomas). Overall recovery of 80% of
      forced expiratory volume in 1 second and forced vital capacity was a median of 3
      days for LAP and 6.0 days for CON (p = 0.01). LAP patients used significantly
      less morphine than CON patients up to the second day after surgery (0.78 +/- 0.32
      versus 0.92 +/- 0.34 mg/kg per day, p = 0.02). Flatus returned a median of 3.0
      days after LAP versus 4.0 days after CON surgery (p = 0.006). Tumor margins were
      clear in all patients. After a median followup of 1.5 years (LAP) and 1.7 years
      (CON), there were no port site recurrences in the LAP group. Seven cancer-related
      deaths have occurred (three in the LAP group, four in the CON group).
      CONCLUSIONS: Within this prospective, randomized trial, laparoscopic techniques
      were as safe as conventional surgical techniques and offered a faster recovery of
      pulmonary and gastrointestinal function compared with conventional surgery for
      selected patients undergoing large bowel resection for cancer or polyps. There
      were no apparent shortterm oncologic disadvantages. Longer followup is needed to
      fully assess oncologic outcomes.

PMID- 9660025
TI  - Laparoscopic versus open resection for colorectal cancer.

PMID- 9660026
TI  - The fate of colonic suture lines in high-risk trauma patients: a prospective
      analysis.
AB  - BACKGROUND: Some authors have stated that virtually all patients with penetrating
      colon injuries can be safely managed with primary repair. The purpose of this
      study is to test the applicability of this statement to all trauma patients by
      evaluating a protocol of liberal primary repair applied to a group of patients at
      high risk of septic complications. STUDY DESIGN: We performed a prospective
      analysis of a liberal policy of primary repair applied to patients at high risk
      of developing postoperative septic complications admitted to a Level I urban
      trauma center. Inclusion criteria were full-thickness colon injury and at least
      one of three additional risk factors: 1) Penetrating Abdominal Trauma Index
      (PATI) of 25 or more; 2) 6 U or more of blood transfused; and 3) 6 hours or
      longer elapsed between injury and surgery. RESULTS: Of 56 patients studied (55
      male, 1 female, average age 28.8 years, mean PATI 35.3), the vast majority had
      gunshot wounds as the mechanism of injury (89%), PATI 25 or more (95%), multiple
      blood transfusions (77%), an Injury Severity Score greater than 15 (66%), and a
      need for postoperative ventilatory support in the surgical intensive care unit
      (61%). Of 56 patients, 49 (88%) had at least one colonic suture line, and 25
      patients (45%) had destructive colon injuries requiring resection. Intraabdominal
      infections occurred in 15 (27%) of 56 patients and colon suture line disruption
      occurred in 3 (6%) of 49. Two of these patients developed multisystem organ
      failure, and death was directly related to breakdown of their colonic
      anastomosis. CONCLUSIONS: On the basis of these data and the relative infrequency
      of patients in prospective randomized trials with destructive colon injuries, we
      believe there is still room for consideration of fecal diversion in patients in
      high-risk categories with destructive colon injuries requiring resection.

PMID- 9660027
TI  - Serum carcinoembryonic antigen as a prognostic factor in resectable gastric
      cancer.
AB  - BACKGROUND: Carcinoembryonic antigen (CEA) has been widely accepted as a tumor
      marker useful in the diagnosis and management of colorectal cancer. When CEA
      levels are positive in gastric cancer patients, they could be useful prognostic
      indicators. However, the value of CEA as a tumor marker for gastric cancer
      remains a matter of controversy. STUDY DESIGN: We measured preoperative serum CEA
      levels in 196 patients with resectable gastric cancer between May 1986 and April
      1996 and then evaluated the correlation between serum CEA levels,
      clinicopathologic features, and prognostic information. RESULTS: Serum levels of
      CEA were above the normal range in 29 of 196 (14.8%) surgically resected patients
      (range, 5.2-570 ng/mL). Among 100 early gastric cancers confined to the
      submucosal layer, only 7 patients (7.0%) had positive CEA levels, but among 96
      advanced cancers, 22 patients (22.9%) had high CEA levels. The CEA positive
      patients had more macroscopically infiltrative tumors, a more prominent serosal
      invasion, more frequent lymph nodes involvement, and a more advanced stage than
      did the CEA negative patients. The 3- and 5-year cumulative disease-specific
      survival rates of patients positive for serum CEA were 39.6% and 31.7%,
      respectively; these rates for patients negative for CEA were 83.0% and 77.3%,
      respectively (p < 0.0001 for comparison of survival curves). In various
      clinicopathologic parameters, nine parameters (tumor size, macroscopic type, type
      and time of operation, Lauren classification, depth of invasion, lymph node
      involvement, CEA, alpha-fetoprotein [AFP], and carbohydrate antigen [CA] 19-9)
      showed statistically significant differences in the cumulative survival rates. Of
      these nine parameters, independent prognostic factors by multivariate analysis
      were depth of invasion (T1, 2 versus T3, 4, p < 0.0001), serum CEA levels
      (negative versus positive, p = 0.0003), and lymph node metastasis (negative
      versus positive, p = 0.0005). CONCLUSIONS: Preoperative serum CEA levels provide
      a predictive value in determining tumor stage and prognostic information for
      patients with potentially resectable gastric cancer during the preoperative
      period.

PMID- 9660028
TI  - Surgical adjuvant active specific immunotherapy for patients with stage III
      melanoma: the final analysis of data from a phase III, randomized, double-blind,
      multicenter vaccinia melanoma oncolysate trial.
AB  - BACKGROUND: A phase III, randomized, double-blind, multicenter trial of active
      specific immunotherapy (ASI) using vaccinia melanoma oncolysate (VMO) was
      performed in patients with stage III (American Joint Commission on Cancer)
      melanoma to determine the efficacy of VMO to increase the disease-free interval
      (DFI) or overall survival (OS) in these patients. Two interim analyses of data
      from this trial were performed in May 1994 and June 1995. Although the results
      from these analyses showed no statistically significant improvement in DFI or OS
      in all patients using VMO, two subsets-men aged 44-57 years with one to five
      positive nodes and all patients with clinical stage I and pathologic stage II
      disease-showed an overall survival advantage with VMO therapy. A final analysis
      of data from this trial was performed in May 1996 and is reported here. The
      design of future melanoma vaccine trials is discussed based on information
      learned from this first randomized, multicenter trial of ASI therapy. STUDY
      DESIGN: A polyvalent VMO was prepared using melanoma cells derived from four
      melanoma cell lines and vaccinia vaccine virus (V). Patients were accrued from 11
      United States institutions and were randomized by the Statistical Center at the
      University of Alabama, Birmingham. Two hundred fifty patients were randomized to
      treatment with either VMO (1 U containing 2 mg of total protein derived from 5 x
      10(6) melanoma cells and 10(5.6) 50% tissue culture infectious dose of vaccinia
      virus) or control V (1 U containing 10(5.4) 50% tissue culture infectious dose of
      vaccinia virus) once a week for 13 weeks and then once every 2 weeks for a total
      of 12 months, or until recurrence. Patient data were collected by the Statistical
      Center and analyzed as of May 1996 for DFI and OS using Wilcoxon test and log
      rank analysis. RESULTS: Two hundred seventeen patients were found to be eligible
      according to the inclusion criteria. Data from these patients were analyzed for
      DFI and OS after a median followup of 46.3 months (50.2 months for VMO and 41.3
      months for V). This final analysis showed no statistically significant increase
      in either DFI (p = 0.61) or OS (p = 0.79) of patients treated with VMO (n = 104)
      compared with V (n = 113). At 2-, 3-, and 5-year intervals, 47.8%, 43.8%, and
      41.7% of patients treated with VMO were disease-free, respectively, compared with
      51.2%, 44.8%, and 40.4% of patients treated with V. At the same intervals, 70.0%,
      60.0%, and 48.6% of patients treated with VMO survived, compared with 65.4%,
      55.6%, and 48.2% of patients treated with V. In a retrospective subset analysis,
      male patients aged 44-57 years (n = 20) with one to five positive nodes showed
      18.9%, 26.82%, and 21.3% improvement in survival at 2-, 3-, and 5-year intervals,
      respectively, after treatment with VMO when compared with V (n = 18) (p = 0.046).
      CONCLUSIONS: This study was a randomized, multicenter, placebo-controlled
      evaluation of an active specific immunotherapeutic agent to increase the DFI or
      OS of patients with stage III melanoma in a surgical adjuvant setting. In this
      trial, ASI with VMO when compared with V showed no difference in either DFI or
      OS. In a retrospective subset analysis, however, a subset of men with one to five
      positive nodes, between the ages of 44 and 57 years, showed a survival advantage
      with VMO. This result suggests that one must include a detailed subset analysis
      in the design of future trials of ASI for patients with American Joint Commission
      on Cancer stage III melanoma. An appropriate control arm also must be included in
      ASI trials.

PMID- 9660029
TI  - Renal pedicle torsion after simultaneous kidney-pancreas transplantation.
AB  - BACKGROUND: Simultaneous kidney-pancreas transplantation has become a recognized
      therapy for type I diabetes mellitus patients with diabetic nephropathy,
      neuropathy, and retinopathy. In the vast majority of these procedures, both
      grafts are placed intraperitoneally, which reduces posttransplant morbidity.
      Recently, in some of our recipients, we noted renal dysfunction related to
      complications of the renal pedicle. Our objectives in this study were to identify
      the cause of this renal dysfunction and to prevent its occurrence in future
      recipients. STUDY DESIGN: We undertook a retrospective chart review of
      simultaneous kidney-pancreas recipients who experienced renal dysfunction related
      to renal pedicle complications. RESULTS: We found four recipients with renal
      dysfunction related to renal pedicle torsion, diagnosed by serial ultrasound
      scans and kidney graft biopsies. Early diagnosis allowed salvage of three kidney
      grafts, but one was lost after late diagnosis. CONCLUSIONS: A high level of
      suspicion is needed to diagnose renal pedicle torsion. If simultaneous kidney
      pancreas recipients have recurrent renal dysfunction, and rejection has been
      excluded, serial ultrasound scans with color flow Doppler examinations are
      needed. Once the diagnosis is made, a nephropexy to the anterior abdominal wall
      is indicated to prevent further torsion and save the kidney graft. We recommend
      prophylactic nephropexy of left renal grafts if the renal pedicle is > or = 5 cm
      long and if there is a 2 cm or more discrepancy between the length of the artery
      and the vein.

PMID- 9660030
TI  - Isolated liver metastases from neuroendocrine tumors: does resection prolong
      survival?
AB  - BACKGROUND: Neuroendocrine tumors commonly metastasize to the liver. Although
      surgical resection is considered a treatment option for patients with localized
      metastases confined to the liver, the longterm survival benefit of liver
      resection has not been clearly demonstrated. We examined the survival of patients
      undergoing liver resection for this disease. STUDY DESIGN: Between 1984 and 1995,
      we evaluated 38 patients with liver-only metastases from neuroendocrine tumors,
      including 21 carcinoid, 13 islet cell, and 4 atypical neuroendocrine neoplasms.
      Data from a combined prospective and retrospective database and a tumor registry
      were analyzed. Of these patients, 15 underwent complete resection of all known
      disease. The remaining 23 patients, who also had disease confined to the liver,
      had comparable tumor burden but were believed to be unresectable. The longterm
      survival rates of these two groups were compared. RESULTS: Patients who underwent
      liver resection did not differ from those who were unresectable with regard to
      age, pathology, primary tumor site, serum alkaline phosphatase levels, or
      percentage of the liver involved. All resections were complete, leaving no
      residual disease, and consisted of lobectomy (n = 3), segmentectomy (n = 1), and
      wedge resections (n = 11). There were no operative deaths. Patients who underwent
      hepatic resection had a significantly longer survival than unresected patients.
      Although median survival had not been reached in resected patients, the median
      survival in the unresectable group was 27 months. Patients who underwent liver
      resection had a higher 5-year actuarial survival (73% versus 29%). CONCLUSIONS:
      Hepatic resection in selected patients with isolated liver metastases from
      neuroendocrine tumors may prolong survival. This conclusion was reached by
      comparing our resected group with an unresectable group with similar tumor
      burden.

PMID- 9660031
TI  - Age as a selection factor for the local therapy of breast cancer?

PMID- 9660032
TI  - Onychocryptosis.

PMID- 9660033
TI  - Two-staged pancreatoduodenectomy with external drainage of pancreatic juice and
      omental graft technique.

PMID- 9660034
TI  - Primary antecubital jump bypass grafts for hemoaccess.

PMID- 9660036
TI  - Effect of grapefruit juice on pharmacokinetics of itraconazole in healthy
      subjects.
AB  - OBJECTIVE: To examine the effect of grapefruit juice on the disposition of oral
      administered itraconazole in healthy subjects. METHODS: Twenty-two healthy male
      subjects received a single 100 mg dose of itraconazole with either 350 ml
      grapefruit juice, orange juice or mineral water. Plasma concentrations of
      itraconazole were measured by HPLC, and pharmacokinetic parameters; Cmax, Tmax,
      T1/2, AUC, and AUC corrected by human body surface area: AUC/S, were calculated.
      RESULTS: Grapefruit juice had no effect on any pharmacokinetic parameter of
      itraconazole. However, T1/2, AUC, or AUC/S were significantly decreased in orange
      juice treatment group compared to those in mineral water group (average decrease
      56%, p < 0.01, 41%, p < 0.05, and 43%, p < 0.05, respectively). CONCLUSION:
      Coadministration of grapefruit juice did not affect any pharmacokinetic parameter
      of itraconazole while that of orange juice decreased the parameters of T1/2, AUC,
      and AUC/S of the drug.

PMID- 9660035
TI  - Zolmitriptan (311C90) does not interact with fluoxetine in healthy volunteers.
AB  - Zolmitriptan (Zomig, formerly 311C90) is a selective 5-hydroxytryptamine (5
      HT)1B/1D-receptor agonist with central and peripheral activity for the acute
      treatment of migraine. This randomized, placebo-controlled, crossover study
      investigated the effects of fluoxetine administration on the pharmacokinetics and
      pharmacodynamics of zolmitriptan. Twenty volunteers were given single doses of
      fluoxetine 20 mg or an identical placebo daily for 28 days prior to receiving a
      single 10 mg oral dose of zolmitriptan. Sixteen volunteers completed the two
      treatment phases. The pharmacokinetic parameters of zolmitriptan and its
      metabolites were not significantly affected by fluoxetine pretreatment. The
      pharmacodynamic effects of zolmitriptan were also unaffected by fluoxetine
      pretreatment. There were small, clinically insignificant increases in blood
      pressure following zolmitriptan which were unaltered by fluoxetine. Zolmitriptan
      was well tolerated when given alone or concomitantly with fluoxetine. These
      results indicate that there is no contraindication to the use of zolmitriptan in
      patients treated concurrently with selective serotonin reuptake inhibitors and
      that no adjustment of the zolmitriptan dose is required in these circumstances.

PMID- 9660037
TI  - Changes of antipyrine pharmacokinetics during influenza and after administration
      of interferon-alpha and -beta.
AB  - OBJECTIVE: During viral infections serum levels of interferons are elevated. In
      this study we wanted to observe the effects of endogenous interferon (IFN) during
      an acute viral infection (influenza) and after external application of
      interferons on the pharmacokinetics of antipyrine which is a parameter of hepatic
      cytochrome P450 enzyme activity. METHODS: Endogenous plasma levels of interferons
      and the antipyrine pharmacokinetics in 10 otherwise healthy volunteers were
      investigated before outbreak and in the symptomatic interval of an acute viral
      respiratory infection. The serum interferon levels were determined by RIA. In
      another trial 2 groups of 9 HIV patients each in stage CDC/WHO B2/3 received low
      dose interferon therapy with 0,75 Mio. I.U. interferon-alpha or -beta s.c./die.
      The concentrations of antipyrine in serum were measured by HPLC. The antipyrine
      kinetics were determined before the infection or the interferon therapy,
      respectively, and during viral infection or during interferon or after interferon
      therapy, respectively. RESULTS: The plasma levels of IFNalpha and IFNgamma were
      significantly elevated from 4.7 U/ml to 12.6 U/ml and 0.3 U/ml to 3.4 U/ml,
      respectively, whereas the antipyrine clearance showed a decrease from 57.9 ml/min
      to 45 ml/min in the symptomatic interval of an acute viral infection. During
      therapy with low-dose interferons we observed a significant difference after 12
      week treatment with IFNalpha or IFNbeta, respectively. In the first group we
      observed a decreased antipyrine clearance from 49.0 ml/min to 41.7 ml/min; in the
      second group the antipyrine clearance decreased from 49.0 ml/min to 41.7 ml/min.
      CONCLUSION: Viral infections (influenza) are able to inhibit the hepatic
      monooxygenase system due to elevated serum interferon levels. Low doses of
      exogenous interferons inhibit the cytochrome P450 monooxygenase system.

PMID- 9660038
TI  - Phase I clinical trial: pharmacokinetics of a novel anthracycline, DA-125 and
      metabolites. Single dose study.
AB  - Single dose of DA-125, 20 (n = 3), 40 (n = 3), 60 (n = 3), 80 (n = 6), or 100 (n
      = 6) mg/m2 body surface area, was administered intravenously in 5 min to 21
      patients with various types of cancer as phase I clinical trial. The main side
      effects of DA-125 were nausea, vomiting, leukopenia (especially neutropenia), and
      thrombocytopenia. Among those, hematological side-effects increased with
      increased doses of DA-125. No patient developed side-effects equal to or higher
      than grade III up to DA-125 dose of 60 mg/m2. However, at DA-125 dose of 80
      mg/m2, 1 out of 3 patients developed grade III leukopenia and grade IV
      neutropenia. Therefore, 3 additional patients participated taking the dose of 80
      mg/m2; no patient developed side-effects equal to or higher than grade III.
      Hence, DA-125 dose increased to 100 mg/m2. At DA-125 dose of 100 mg/m2, 2 out of
      3 patients developed side-effects equal to or higher than grade III and,
      therefore, 3 additional patients participated taking this dose. Among the 3
      additional patients, 1 patient developed both grade III leukopenia and
      neutropenia. Therefore, further accrual was stopped at this dose (100 mg/m2). The
      maximally tolerated dose (MTD) of DA-125 was determined to be 100 mg/m2, and the
      dose-limiting factor for DA-125 was bone marrow suppression. DA-125 dose of 80
      mg/m2, 80% of MTD of DA-125, was recommended as the dose for phase II clinical
      trial. Cardiotoxicity was not observed in any of the 21 patients according to the
      ECG and RVG. Neither fever, stomatitis, diarrhea, and renal and nervous system
      toxicity, nor abnormality in blood coagulation was observed in any of the
      patients, and death or life-threatening side-effects due to DA-125 were also not
      observed. Antitumor effects of DA-125 were evaluated from the 21 patients; 6
      progressive disease, 14 stable disease, and 1 partial response. Pharmacokinetic
      parameters of M1, such as AUC, t1/2, CL, VSS, and MRT, seemed to be independent
      of i.v. doses of DA- 125, 20-100 mg/m2 and less than 0.75% of M1 were excreted in
      96 h urine when expressed in terms of DA-125 i.v. dose. M2 was the main
      metabolite of DA-125 among M1-M4 excreted in urine; 10.1 approximately 22.3% of
      M2 was excreted in 96 h urine when expressed in terms of DA-125 i.v. dose. Bile
      was collected via the T-tube in 1 additional patient at the dose of 100 mg/m2.
      Biliary excretion of M1 and M2 was negligible; less than 0.320 and 4.76% of M1
      and M2, respectively, were excreted in 96 h bile when expressed in terms of DA
      125 i.v. dose.

PMID- 9660039
TI  - Comparative study of tolerability and efficacy of iron protein succinylate versus
      iron hydroxide polymaltose complex in the treatment of iron deficiency in
      children.
AB  - One-hundred children, 48 males and 52 females, mean age +/- SD 39.9 +/- 28.2
      months (range 12 to 113) with sideropenia or sideropenic anemia were randomly
      divided into 2 groups of 50 patients each (groups A and B) and were treated with
      iron protein succinylate (group A) or iron hydroxide polymaltose complex (group
      B). Patients of both groups received 4 mg/kg elemental iron, maximally 80 mg
      daily, for 2 months. Side-effects of therapy and laboratory values (RBC,
      hematocrit, hemoglobin, MCV, serum iron, total iron binding capacity, and
      ferritin) were registered before treatment, 30 days after the beginning of
      therapy as well as after 60 days in order to evaluate tolerability and efficacy
      of the drugs. Both drugs were well tolerated and showed only few adverse
      reactions, which were comparable in severity and frequency. Iron protein
      succinylate led not only to a faster increase of hemoglobin, hematocrit, MCV,
      serum iron, and ferritin than iron hydroxide polymaltose complex, but the
      laboratory values remained higher in group A than in B even after 2 months of
      treatment.

PMID- 9660040
TI  - Efficacy and safety of one-year treatment with slow-release nicotinic acid.
      Monitoring of drug concentration in serum.
AB  - The paper is aimed at evaluation of the efficacy and safety of one-year therapy
      with slow-release nicotinic acid (NA-SR). The study involved a group of 30
      patients with hyperlipidemia of type II. The concentration of nicotinic acid in
      serum was determined using capillary electrophoresis. After the placebo period (2
      months), NA-SR was applied at the dose of 1.5 g/d (2 months), and subsequently 2
      3 g/d (10 months), on average 2.13 g/d. During the treatment with 2.0 g/d dose,
      the steady-state concentration of NA in serum was within a range of 2.7-4.9
      microg/ml and with 3.0 g/d of 6.17-7.75 microg/ml. These doses of the drug were
      tolerated well and advantageously modified the serum lipids.

PMID- 9660041
TI  - Hyponatremia following acute overdose with paroxetine.
AB  - This case illustrates severe hyponatremia following an acute overdose of
      paroxetine. An 83-year-old woman was admitted to our hospital after an attempt to
      commit suicide. She had consumed an overdose of 360 mg paroxetine. The treatment
      was started 3 days previously with 10 mg/day because of regular suffering from
      obsessive and suicidal thoughts. An initial sign of overdose was excessive
      vomiting. Five days late she developed hyponatremia (serum sodium 112 mmol/l)
      with somnolence, confusion, muscle spasms, dehydration of arms and legs and slow
      reflexes. Ecchymoses and myxoedema were also observed. Treatment included fluid
      restriction and sodium chloride infusion. Levothyroxin was prescribed and the
      hyponatremia resolved.

PMID- 9660042
TI  - Comparison of psychomotor functions and sedation following premedication with
      oral diazepam and clonidine in children.
AB  - In a prospective, double-blind, controlled, randomized study, the psychomotor
      functions and sedation were assessed after premedication with diazepam and
      clonidine in children. Forty children in the age-group of 5-8 years, undergoing
      elective surgery under general anesthesia were studied. Twenty children (group 1)
      received oral clonidine 4 microg/kg, and 20 children (group 2) received oral
      diazepam 0.2 mg/kg, 120 minutes before induction of anesthesia. Sedation and
      psychomotor functions were assessed in both groups, before and after 60-90
      minutes of administration of premedication. The results of the study showed that
      mean sedation score in group 1 was 8 +/- 1.07, and 9 +/- 0.64 in group 2. On
      intergroup comparison the sedation was found to be comparatively better in group
      2 than group 1 (p < 0.05). The performance of psychomotor functions decreased
      after premedication in both the groups as compared to that before premedication
      (p < 0.05). The psychomotor functions were depressed more in diazepam group than
      in the clonidine group (p < 0.05). Thus, it is concluded that clonidine produces
      good sedation and causes less effect on psychomotor functions and therefore can
      be used for premedication in children.

PMID- 9660043
TI  - Comparative study of different weighting methods in non-linear regression
      analysis: implications in the parametrization of carebastine after intravenous
      administration in healthy volunteers.
AB  - The influence of different weighting methods in non-linear regression analysis
      was evaluated in the pharmacokinetics of carebastine after a single intravenous
      dose of 10 mg in 8 healthy volunteers. Plasma concentrations were measured by
      HPLC using an on-line solid-phase extraction method and automated injection. The
      analytical method was fully validated and the function of the analytical error
      subsequently determined. The parametric approach was performed using different
      weighting methods, including the homoscedastic method (W = 1) and heteroscedastic
      methods using weights of 1/C, 1/C2, and the inverse of the concentration variance
      calculated through the analytical error function (1/V), and the results were
      statistically evaluated according to the normal distribution. Statistically
      significant differences were observed in the representative parameters of the
      disposition kinetics of carebastine. The use of a multiple comparison test for
      statistical analysis of all differences among group means indicated that
      differences were generated between the homoscedastic method (W = 1) and the
      heteroscedastic methods (1/C, 1/C2, and 1/V). The results obtained in the present
      study confirmed the utility of the analytical error function as a weighting
      method in non-linear regression analysis and reinforced the importance of the
      correct choice of weights to avoid the estimation of imprecise or erroneous
      pharmacokinetic parameters.

PMID- 9660045
TI  - Amiodarone-induced severe hepatitis mediated by immunological mechanisms.
AB  - A 64-year-old man developed a fulminant hepatitis 4 days after initiation of
      amiodarone treatment and a total dose of 7.1 g. The direct Coombs test was
      positive and became negative again soon after stopping treatment. Immediately
      after stopping treatment the extremely increased parameters of hepatic failure
      returned to normal again. A rechallenge with 200 mg of amiodarone was accompanied
      by a positive Coombs test which again became negative after several days. We
      conclude that the occurrence of an acute hepatitis soon after initiation of
      amiodarone treatment is mediated by immunological mechanisms. There should be
      high vigilance with respect to this rare life-threatening adverse drug reaction.

PMID- 9660044
TI  - Effects of fenofibrate on plasma cytokine concentrations in patients with
      atherosclerosis and hyperlipoproteinemia IIb.
AB  - BACKGROUND AND OBJECTIVE: In recent studies atherosclerosis has often been
      referred to as immune disease. The atherosclerotic plaque consists of large
      amounts of inflammatory cells, mainly monocytes/macrophages and T lymphocytes.
      Macrophages activated by low-density lipoproteins (LDL) secrete tumor necrosis
      factor alpha (TNF-alpha) and interleukin-1 (IL-1) in vitro, while LDL-stimulated
      T lymphocytes release interferon gamma (IFN-gamma). The aim of this study was to
      estimate the plasma levels of TNF-alpha, IL-1, IFN-gamma in patients with
      hyperlipoproteinemia IIb (HLPIIb) and atherosclerosis. Since the fibrates are
      drugs of choice in HLPIIb, we additionally evaluated the effect of fibrates on
      the cytokine levels. METHODS: Ten patients with HLPIIb were treated with
      micronized fenofibrate for 1 month. Before and after treatment, the cytokine
      levels were measured by the ELISA method. To accurately evaluate cytokine levels,
      we excluded atherosclerotic patients and control subjects with any inflammatory
      disease. RESULTS: The initial lipid parameters were as follows: total cholesterol
      (TC): 6.9 +/- 0.24 mmol/l, triglycerides (TG): 3.44 +/- 0.53 mmol/l, LDL: 4.35 +/
      0.12 mmol/l, and apolipoprotein B (ApoB): 1.62 +/- 0.05 g/l. After 1 month of
      fenofibrate treatment the parameters decreased to the following values: TC 5.36
      +/- 0.42 mmol/l (p < 0.05), TG 1.94 +/- 0.30 mmol/l (p < 0.05), ApoB 1.43 +/-
      0.04 g/l (p < 0.01), and LDL 3.75 +/- 0.34 mmol/l (p > 0.05). Before therapy, TNF
      alpha levels in atherosclerotic patients were higher than in control subjects,
      19.2 +/- 1.6 and 9.9 +/- 1.1 pg/ml, respectively (p < 0.01). After 1-month
      therapy, TNF-alpha levels in atherosclerotic patients were 9.2 +/- 1.0 pg/ml (p <
      0.01). Similarly, the initial levels of IFN-gamma were higher in atherosclerotic
      patients compared with healthy subjects, 44.4 +/- 5.3, and 19.4 +/- 2.1 pg/ml,
      respectively (p < 0.01). After fenofibrate therapy, IFN-gamma levels decreased to
      24.8 +/- 2.9 pg/ml (p < 0.01). The decreased levels of TC, TG, and LDL correlated
      with the decreased levels of TNF-alpha and IFN-gamma. CONCLUSION: The results of
      this study indicate that plasma TNF-alpha and IFN-gamma levels in hyperlipidemic
      patients are higher than in healthy subjects, and that fenofibrate is effective
      in decreasing lipids and cytokines in plasma.

PMID- 9660046
TI  - An alternative analysis for crossover studies that accounts for between-group
      disparities in drug response--corrigenda.

PMID- 9660047
TI  - Internet databases for clinical geneticists--an overview.
AB  - In this paper, we provide an overview of databases that are of importance to
      clinical geneticists. Some suggestions for the fruitful use for both research and
      diagnosis are given. For beginning 'web-surfers' we also list some well-known
      search engines and give a short overview of how to use these and other services.
      In addition, the URLs of some of the most important databases, gateways and
      tutorials are listed.

PMID- 9660051
TI  - Limb development: molecular dysmorphology is at hand!
AB  - We present a review of limb development integrating current molecular information
      and selected genetic disorders to illustrate the advances made in this field over
      the last few years. With this knowledge, clinical geneticists can now begin to
      consider molecular mechanisms and pathways when investigating patients with limb
      malformation syndromes.

PMID- 9660052
TI  - Murine MPS I: insights into the pathogenesis of Hurler syndrome.
AB  - Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disease resulting
      from deficiency of the lysosomal enzyme alpha-L-iduronidase. A murine model which
      shows complete deficiency in alpha-L-iduronidase activity has been developed and
      shows phenotypic features similar to severe MPS I in humans. Here we report on
      the long-term clinical, biochemical, and pathological course of MPS I in mice
      with emphasis on the skeletal and central nervous system (CNS) manifestations.
      Affected mice show a progressive clinical course with the development of coarse
      features, altered growth characteristics and a shortened life span. Progressive
      lysosomal accumulation is seen in all tissues. Skeletal manifestations represent
      the earliest clinical finding in MPS I mice with histologic analysis of growth
      plate and cortical bone revealing evidence that significant early pathology is
      present. Analysis of the CNS has revealed the novel finding of progressive
      neuronal loss within the cerebellum. In addition, brain tissue from MPS I mice
      shows increased levels of GM2 and GM3 gangliosides. This murine model clearly
      shows phenotypic and pathologic features which mimic those seen in severe human
      MPS I and should be an invaluable tool for the study of the pathogenesis of
      generalized storage disorders.

PMID- 9660053
TI  - Identification of iduronate sulfatase gene alterations in 70 unrelated Hunter
      patients.
AB  - We studied 70 unrelated Hunter patients and found a gene alteration in every
      patient. The molecular heterogeneity was very important. Large gene
      rearrangements were identified in 14 patients. Forty-three different mutations
      were identified in the 56 other patients and 31 were not previously described.
      Deletions and insertions, splice site mutations were associated with a severe
      phenotype as nonsense mutations except Q531X. Only a few mutations were present
      in several patients making difficult genotype-phenotype correlations. Mutation
      identification allows accurate carrier detection improving prenatal diagnosis.
      The mother was not found to be a carrier in five cases among the 44 sporadic
      cases. Haplotype analysis demonstrated a higher frequency of mutations in male
      meiosis.

PMID- 9660054
TI  - Clinical, biochemical and molecular findings in a two-generation Morquio A
      family.
AB  - Mucopolysaccharidosis type IVA (Morquio A) is caused by a deficiency of N
      acetylgalactosamine-6-sulfatase (GALNS), an enzyme capable of cleaving the
      sulfate group from both N-acetylgalactosamine-6-sulfate and galactose-6-sulfate.
      We describe here a two-generation Morquio A family with two distinct clinical
      phenotypes. The two probands from the second generation showed intermediate signs
      of the disease whereas their affected mother, aunt and two uncles had only very
      mild symptoms. Galactose-6-sulfatase (GALS) activity in leukocytes and
      fibroblasts of the affected family members was clearly deficient. Molecular
      genetic analysis of the GALNS gene revealed that two different point mutations
      segregate in the family, which correlated well with the clinical phenotype. The
      probands with intermediate symptoms were compound heterozygotes for the mutations
      R259Q and R94G, the latter one being inherited from the unaffected father. The
      mother and her affected siblings with the unusually mild phenotype were proven to
      be homozygous for the novel missense point mutation R259Q.

PMID- 9660055
TI  - Applicability of LDLR flanking microsatellite polymorphisms for prenatal
      diagnosis of homozygous state for familial hypercholesterolemia.
AB  - Analysis of newly identified microsatellite polymorphisms flanking the low
      density lipoprotein receptor (LDLR) gene was undertaken in the kindred of a child
      with apparent homozygous LDLR deficiency. The applicability of these approaches
      to prenatal diagnosis is considered and compared with previous approaches
      applying functional studies of the LDLR in amniotic fibroblasts.

PMID- 9660056
TI  - Glycogen storage disease type II: identification of a dinucleotide deletion and a
      common missense mutation in the lysosomal alpha-glucosidase gene.
AB  - In nine Dutch patients with the infantile form of glycogen storage disease type
      II (GSDII), who were compound heterozygous for either 525delT or exon18del (1),
      sequence analysis was performed to search for the mutations in the second
      lysosomal alpha-glucosidase allele. One patient had a novel TG deletion at cDNA
      position 379 + 380. Surprisingly five of the nine patients had the same two base
      pair changes: A921 --> T and G925 --> A. The first change is a well-known
      polymorphism but the second one is a novel mutation and results in the
      substitution of Gly309 by Arg. By screening 43 other GSDII patients the same
      mutation was found in two other cases, one from The Netherlands and one from
      France. To verify its deleterious effect, the mutation was introduced in the wild
      type lysosomal alpha-glucosidase cDNA and expressed in COS cells.

PMID- 9660057
TI  - Mild cystic fibrosis mutations in Southern Sweden with special reference to S549I
      and T338I.
AB  - In this study of cystic fibrosis (CF) gene mutations in Southern Sweden we found
      missense mutations in 12 out of 110 patients. These patients, as a group,
      differed from deltaF508 homozygotes by a higher frequency of pancreatic
      sufficiency and an older age at diagnosis as has been indicated in previous
      studies. In addition, lung function (vital capacity (VC) and forced expiratory
      volume in 1 s (FEV1)) tended to be better although the difference did not reach
      statistical significance (p = 0.13 for FEV1). For two mutations, S549I and T338I,
      our results differed from earlier reports. In our experience, S549I confers a
      milder phenotype and T338I a more severe one than previously reported. We
      conclude that each mutation should be treated separately when trying to correlate
      genotype with phenotype.

PMID- 9660058
TI  - Apolipoprotein E genotypes in offspring with a positive and negative family
      history of premature myocardial infarction.
AB  - Apolipoprotein E (apo-E) allele and genotype frequencies were evaluated in
      offspring with positive (MI-offspring) and negative (control-offspring) parental
      history of myocardial infarction (MI). The apo-E allele frequencies in MI- and
      control-offspring were as follows: epsilon2: 9.04 and 2.08% (p < 0.02), epsilon3:
      84.04 and 87.5%, epsilon4: 6.91 and 10.41%, respectively. The frequencies of the
      E2-genotypes were significantly lower in offspring of controls (4.2%, 17.0%,
      respectively, p < 0.03). The epsilon2-allele is associated with raised plasma
      triglyceride concentrations in subjects on a diet high in saturated fat. We
      therefore hypothesize that offspring carrying an epsilon2-allele are predisposed
      to develop disturbance of plasma triglyceride metabolism when exposed to a
      traditional Slovak high-fat diet and/or weight gain, resulting in altered lipid
      levels and increased predisposition to atherosclerosis.

PMID- 9660059
TI  - A 'de novo' point mutation of the low-density lipoprotein receptor gene in an
      Italian subject with primary hypercholesterolemia.
AB  - Severe hypercholesterolemia was found in an 11-year-old boy with no family
      history of familial hypercholesterolemia. The reduced LDL-receptor activity in
      cultured skin fibroblasts (40% 125I-LDL degradation as compared with a control
      cell line) indicated the presence of an LDL-receptor defect. The analysis of the
      promoter region and the exons of LDL-receptor gene by single strand conformation
      polymorphism revealed an abnormal migration pattern in exon 1, which was due to a
      T --> A transversion at nucleotide 28 of the cDNA. This novel mutation causes an
      arginine for tryptophane substitution at position - 12 of the signal peptide (W
      12R) and introduces an AviII restriction site in exon 1. Screening of the
      mutation by polymerase chain reaction (PCR) amplification of exon 1 and AviII
      digestion revealed that none of the proband's family members carried the
      mutation. Non-paternity was excluded after the analysis of a battery of 14 short
      tandem repeats located in 13 different chromosomes. These results are consistent
      with the hypothesis that the proband is heterozygous for a 'de novo' mutation of
      the LDL-receptor gene producing a non-conservative amino acid substitution. We
      suggest that the change in the net charge of the signal peptide, caused by the
      addition of a positively charged amino acid, impairs the co-translational
      translocation of the nascent receptor protein across the endoplasmic reticulum
      membrane.

PMID- 9660060
TI  - Genotyping of the polymorphic N-acetyltransferase (NAT2) and loss of
      heterozygosity in bladder cancer patients.
AB  - Acetylation is one of the major routes in metabolism and detoxification of a
      large number of drugs, chemicals and carcinogens. Slow acetylators are said to be
      more susceptible to developing bladder cancer and because of investigations about
      tumor risk based on phenotyping procedures, it was our aim to study the
      distribution of allelic constellations of the N-acetyltransferase (NAT2) by
      genotyping patients with bladder cancer. We analysed NAT2 gene of blood and tumor
      DNA from 60 patients with primary bladder cancer and DNA of blood samples from
      154 healthy individuals. Using ASO-PCR/RFLP techniques we identified 70% of
      patients with bladder cancer (n = 42) to be slow acetylators while genotyping of
      controls resulted in 61% with slow acetylators (n = 94). In addition, dividing
      bladder cancer patients in males and females the genotype NAT2*5B/NAT2*6A occured
      with much higher frequencies in males (OR = 4, 95%); CI = 1.8-8.9). Furthermore,
      investigating bladder cancer tissues we could detect loss of heterozygosity (LOH)
      in slow and rapid acetylator genotypes. In eleven out of 60 tumor samples (18.3%)
      we observed allelic loss at the NAT2 locus while in control DNA of blood from the
      same patients both alleles were still detectable.

PMID- 9660061
TI  - Partners with reciprocal translocations: genetic counseling for the 'double
      translocation'.
AB  - SV at age 2 years presented with multiple congenital anomalies including an
      absent left kidney, anal stenosis, vertebral abnormalities, partial sacral
      agenesis, microcephaly, dysmorphic facial features, growth deficiency, and
      developmental delay. She was found to have a complex chromosomal rearrangement
      derived from balanced translocations in each parent.

PMID- 9660062
TI  - Deletion in chromosome region 22q11 in a child with CHARGE association.
AB  - We present a female child with features of the CHARGE association, including iris
      coloboma, large ventricular septum defect (VSD), external ear abnormalities,
      severe growth retardation and moderate mental delay. A submicroscopic deletion in
      chromsome 22q11 was detected by means of fluorescence in situ hybridization
      (FISH) using probe DO832. The clinical features in this child compromise
      characteristics of both the velo-cardio-facial syndrome (VCFS) and the cat-eye
      syndrome. This may suggest the presence of a more complex rearrangement of 22q,
      with a deletion-duplication.

PMID- 9660063
TI  - Noonan syndrome associated with central giant cell granuloma.
AB  - We report a case of Noonan syndrome associated with central giant cell granuloma.
      The patient was a 10 1/2-year-old boy with the chief complaint of proptosis of
      the right eye. He also had various malformations such as short stature, webbed
      neck, pectus excavatum, cubitus valgus, pulmonary valve stenosis and patent
      foramen ovale, a characteristic face appearance and cryptorchidism and so on.
      Chromosome analysis showed a 46,XY karyotype. A computed tomographic scan and
      magnetic resonance imaging showed a mass originated from the lateral wall of the
      right maxillary sinus. The patient underwent Caldwell-Luc operation. Histological
      examination of the mass showed the characteristics of central giant cell
      granuloma. This case report describes a patient with the features of the recently
      described Noonan-like/multiple giant cell lesion syndrome.

PMID- 9660064
TI  - Jumping translocation with partial duplications and triplications of chromosomes
      7 and 15.
AB  - We report a 2-year-old female with seizures, mild dysmorphic features and a
      jumping translocation involving chromosome 15 that results in multiple cell lines
      with partial duplications and triplications of chromosomes 7 and 15. Fluorescent
      in situ hybridization (FISH) and chromosome microdissection were used to identify
      the complex nature of the jumping translocation. Interstitial telomeres were
      observed at the jumping translocation sites. The jumping chromosome rearrangement
      was also found to have a partial duplication of 7p as demonstrated by chromosome
      microdissection. Despite these partial duplications and triplications of
      chromosomes 7 and 15, the child does not have major birth defects. She does have
      mild sensorimotor delays. A review of non-Robertsonian jumping translocations is
      provided.

PMID- 9660065
TI  - Neuronal nitric oxide synthase, nNOS, is not linked to infantile hypertrophic
      pyloric stenosis in three families.

PMID- 9660066
TI  - The persistent elevated cytokine mRNA levels in trigeminal ganglia of mice
      latently infected with HSV-1 are not due to the presence of latency associated
      transcript (LAT) RNAs.
AB  - Trigeminal ganglia (TG) from mice latently infected with wild type HSV-1 contain
      detectable levels of cytokine transcripts that are not present in TG from
      uninfected mice. This suggests that during HSV-1 neuronal latency, the immune
      system is stimulated by the production of one or more viral proteins. Since the
      LAT (latency associated transcript) gene is essential for wild type levels of
      spontaneous reactivation and is the only highly active viral gene during latency,
      the stimulation of cytokines may indicate the presence of a LAT encoded latency
      protein. We therefore compared the cytokine transcript profiles in the TG of mice
      latently infected with wild type and LAT negative viruses. Mice were latently
      infected with either: (1) the LAT null mutant dLAT2903; (2) its marker rescued
      virus dLAT2903R; or (3) the parental wild type HSV-1 strain McKrae. As expected,
      reactivation following explant cultivation of TG from latently infected mice was
      significantly decreased with dLAT2903 (P < 0.05)(40 +/- 8%, n = 24) compared with
      dLAT2903R (85 +/- 7.6%, n = 36) or the parental virus (70 +/- 10.0%, n = 36). The
      relative levels of various cytokines was determined by RT-PCR analysis of TG
      extracts. None of the cytokine transcripts detected in mice latently infected
      with the wild type or marker rescued viruses were missing or decreased in mice
      latently infected with the LAT null mutant 30 or 60 days post infection. There
      were also no differences in the HSV-1 antibody titers induced by the LAT negative
      virus compared to the LAT positive viruses. Thus, although LAT facilitated
      reactivation of HSV-1 from explanted mouse TG, expression of LAT during latency
      did not appear to be involved in persistent cytokine expression in TG. This
      suggests that during latency, HSV-1 does not produce a highly antigenic abundant
      LAT encoded protein.

PMID- 9660067
TI  - Molecular variation in the nucleoprotein gene (ORF7) of the porcine reproductive
      and respiratory syndrome virus (PRRSV).
AB  - The nucleoprotein gene (ORF7) of 15 European isolates of porcine reproductive and
      respiratory syndrome virus (PRRSV) was sequenced and compared with corresponding
      sequences of other PRRSV isolates (2 European and 13 American) and one isolate
      each of other arteriviruses (the lactate dehydrogenase elevating virus (LDV), the
      simian haemorrhagic fever virus (SHFV) and the equine arteritis virus (EAV)).
      Their phylogenetic relationships were established using neighbour-joining and
      parsimony methods. Four lineages (PRRSV, LDV, SHFV and EAV) were discriminated.
      Two genotypes of PRRSV, European and American, could be further identified. The
      European genotype of PRRSV was highly conserved. Analysis of the nucleotide and
      amino acid substitutions in PRRSV ORF7 revealed four stable regions, probably
      conserved because of their requirement for nucleocapsid function and/or
      structure. No constant mutations accumulation in the ORF7 could be determined
      precisely when either synonymous or non-synonymous mutations were studied.
      Passage of the European PRRSV in vivo had little influence on the ORF7 sequence:
      only a small number of synonymous substitutions in ORF7 was detectable,
      confirming its low variability.

PMID- 9660069
TI  - Expression of the human immunodeficiency virus gag gene products by a replication
      incompetent herpes simplex virus vector.
AB  - A recombinant replication-incompetent herpes simplex virus vector (vd120/Gag)
      that expressed the human immunodeficiency virus 1 gag gene and part of the pol
      gene that encodes the HIV-1 protease was constructed. Examination of cells
      infected with vd120/Gag revealed the presence of the Gag polyprotein Pr55gag by
      12 h post-infection, as well as abundant levels of the proteolytically processed
      24-kDa capsid protein. Analysis of vector-infected cells and culture supernatant
      indicated that the majority of the 24-kDa protein remained cell-associated.
      Although the HIV-1 Gag polyprotein was produced in vd120/Gag-infected cells,
      there was no evidence of HIV virus-like particle production upon examination of
      vector-infected cells by transmission electron microscopy.

PMID- 9660068
TI  - Synthetic peptides of human papillomavirus type 18 E6 harboring HLA-A2.1 motif
      can induce peptide-specific cytotoxic T-cells from peripheral blood mononuclear
      cells of healthy donors.
AB  - To identify cytotoxic T-cell (CTL) epitopes against human papillomavirus type 18
      (HPV 18) E6 protein that might be useful for developing peptide-based vaccine
      against HPV 18 infection, 18 peptides which possibly contain CTL epitopes were
      selected on the basis of previously described human leukocyte antigen (HLA)-A2.1
      binding motif and chemically synthesized. In the binding assay of the synthetic
      peptides, 8 out of 18 synthetic peptides enhanced the expression of HLA-A2.1
      molecules on T2 cell surface, which implies that these peptides were able to bind
      the HLA molecules. Those peptides having good binding affinity to HLA-A2.1 were
      tested for their ability to activate CTLs which were isolated from peripheral
      blood mononuclear cells (PBMCs) of healthy blood donors and to kill the target T2
      cells pulsed with the same peptide. Five out of eight tested peptides activated
      CTLs and killed the target cells.

PMID- 9660070
TI  - The capsid protein of vesicular exanthema of swine virus serotype A48:
      relationship to the capsid protein of other animal caliciviruses.
AB  - Vesicular exanthema of swine virus (VESV), the prototype calicivirus, is the
      etiologic agent of the porcine disease vesicular exanthema of swine (VES). VES is
      characterized by vesicle formation on the extremities, mouth and snout and causes
      abortions and stillbirths if infection occurs during pregnancy. VESV is
      considered an exotic agent in the US, following its eradication in 1956. The
      single capsid protein gene of VESV serotype A48 was cloned and sequenced. The
      capsid amino acid sequence was 69% similar to the San Miguel sea lion virus
      serotype 1 (SMSV 1) and 89% similar to the SMSV serotype 4 (SMSV 4) capsid
      proteins. The six functional regions (A-F) previously identified in SMSV 1, SMSV
      4, feline calicivirus and rabbit hemorrhagic disease virus capsid proteins were
      present in VESV A48. Two sets of PCR primers were designed which directed
      amplification of the 5' end (A region) and the hypervariable (E region) sequences
      of the capsid protein precursor gene of these viruses, as well as seven
      additional SMSV serotypes. Alignment and phylogenetic analysis of the N-terminal
      sequences demonstrated the close relationship of these viruses. Alignment of the
      hypervariable region amino acid sequences of the ten viruses confirmed that a
      great variety of sequence exists in this region; however, a consensus sequence
      (NxT(N/H)F(K/R)GxYI(C/M)GxLx(T/R)) was derived which is also present in the
      feline calicivirus capsid protein. Comparison of the E region sequences provides
      further evidence that this area of animal calicivirus capsid protein may contain
      the major antigenic determinants.

PMID- 9660071
TI  - Persistent infection with an influenza C virus variant is dominantly established
      in the presence of the parental wild-type virus.
AB  - Two influenza C viruses were used for double-infection experiments to investigate
      the dominance of their phenotypes. The wild-type virus (C/AA-wt) had been
      characterized by its short-lived productive cycle, whereas a distinct variant
      derived from it (C/AA-pi) was demonstrated to persist in long-term passages of
      infected MDCK cultures. Here we show that the persistent virus C/AA-pi is capable
      of replicating in the presence of abundant amounts of wild-type virus: the
      persistent virus could be diluted to 10(-9) within wild-type inoculum, still
      developing a stable form of persistence. This behaviour was reflected by
      permanent virus release and by continuous enzymatic activity of the viral HEF
      glycoprotein in infected cells. All long-term cultures tested remained positive
      for viral NS protein and vRNA. On the vRNA level, it was shown that viral
      segments originated from the persistent-type genome, while wild-type vRNAs were
      not maintained after double-infection. Thus, the genotype of the persistent
      variant was dominantly selected in serial passages. These results indicate a
      specific intracellular advantage of persistent influenza C virus over the
      parental wild-type.

PMID- 9660072
TI  - Multiple alignment comparison of the non-structural genes of influenza A viruses.
AB  - One hundred and six influenza A virus isolates were compared phylogenetically
      using gene segment 8 which encodes the two non-structural (NS) proteins, NS1 and
      NS2. The isolates separated into two previously described subtypes, A and B. For
      non-structural gene subtype A viruses, five subdivisions were distinguished in
      the nucleotide phylogenetic tree including a human-swine group, American avian
      equine group, Eurasian avian-swine group, a unique gull isolate group, and a
      group with a single member, A/Equine/Prague/56. At the nucleotide sequence level
      the B subtype was subdivided into two groups, including the American avian group
      and Eurasian avian-equine group. In the analysis of the NS1 and NS2 predicted
      amino acid sequence, American and Eurasian influenza isolates became less
      distinguishable. Size variability of the NS1 protein was observed, especially in
      the human and swine isolates. The previously reported deletion in
      A/Turkey/Oregon/71 NS1 gene, which caused a truncated NS1 protein, was contrasted
      with a full length NS1 gene cloned from an earlier A/Turkey/Oregon/71 stock. All
      avian origin influenza viruses had a putative NS1 sequence length of 230 aa, with
      two exceptions, A/CK/Pennsylvania/1370/83 and A/CK/Pennsylvania/21525/83, with an
      NS1 protein of 217 aa.

PMID- 9660073
TI  - In vivo evolution and selection of recombinant feline leukemia virus species.
AB  - Ecotropic feline leukemia viruses subgroup A (FeLV-A) is known to recombine with
      endogenous FeLV (enFeLV) env elements yielding polytropic FeLV-B viruses.
      However, scattered nucleotide differences exist between enFeLV env elements and
      corresponding sequences of exogenous FeLV-B isolates. To address this disparity,
      we examined recombinant FeLV (rFeLV) viruses obtained from three experimentally
      induced feline thymic tumors, along with rFeLVs derived from one naturally
      occurring thymic tumor. Two of the three experimental cats were challenged with a
      FeLV-A/Rickard preparation, while one cat received this FeLV-A along with a
      mixture of in vitro-generated rFeLVs. The FeLV-A/Rickard preparation employed in
      this study was shown to be free of detectable rFeLVs since no recombinant
      products were observed in this preparation following nested PCR analyses. For
      each of the four tumor DNAs, nucleotide sequence analysis was performed on
      multiple clones of rFeLV-specific PCR products derived from the surface
      glycoprotein (SU) portion of the recombinant proviral env gene. Relative to the
      parental enFeLV sequence used to generate the rFeLVs, a total of 19 nucleotide
      differences were found scattered within the SU region of the env gene in these in
      vivo-derived rFeLV clones. Most interestingly, this set of 19 differences led to
      complete sequence identity with natural FeLV-B isolates. Our results indicate
      these differences are present early in the in vivo evolution of recombinant
      viruses, suggesting that rFeLVs harboring these differences are strongly
      selected. We also present evidence indicating an in vivo selection pattern exists
      for specific recombinant species containing relatively greater amounts of enFeLV
      derived SU sequence. This in vivo selection process appears to be gradual,
      occurring over the infection timecourse, yielding rFeLV species which have
      recombination structural motifs similar to those seen in natural FeLV-B isolates.

PMID- 9660074
TI  - Development and application of polymerase chain reaction (PCR) tests for the
      detection of subgroup J avian leukosis virus.
AB  - Subgroup J avian leukosis virus (ALV) is a recently identified avian retrovirus
      associated with myeloid leukosis in meat-type chickens. The env gene of the HPRS
      103 strain of ALV, the prototype of this subgroup, differs considerably from that
      of other subgroups, but shows close homology to the env-like sequences of members
      of the EAV family of endogenous retroviruses. Polymerase chain reaction (PCR)
      tests using two sets of primers were developed for the specific detection of the
      members of this new subgroup along with another pair of primers for detecting
      other subgroup viruses. The specificity and sensitivity of this detection system
      was compared with the conventional detection methods in experimentally and
      naturally infected samples. The use of PCR was found to be rapid, specific and
      more sensitive than the conventional diagnostic tests for the detection of ALV.
      Moreover, the two subgroup J ALV-specific PCR tests were found to be capable of
      differentiating between 'prototype-like' viruses and more recent isolates which
      show extensive antigenic and sequence variations. The use of this test as a rapid
      and sensitive method of detection of viruses in epidemiological studies and
      eradication programs is discussed.

PMID- 9660075
TI  - Amino acids 1-29 of the adenovirus serotypes 12 and 2 E1A proteins interact with
      rap30 (TF(II)F) and TBP in vitro.
AB  - Early region 1A (E1A) gene products of adenoviruses (Ad) play an essential role
      in both productive infection and cellular transformation. Besides their function
      to induce the expression of all other adenoviral genes they modulate the
      expression of specific cellular genes to ensure an efficient viral reproduction.
      Gene regulatory functions of E1A proteins are mainly located in the conserved
      regions 1-3 (CRs) and in the non-conserved amino terminal end and are mediated
      via protein/protein interactions with cellular factors. We could show recently,
      that the E1A N-terminus (amino acids [aa] 1-29) of oncogenic Ad12 contains a
      unique 'trans'-activation domain. Here we demonstrate that this region binds to
      rap30/TF(II)F and to the TATA-box binding protein TBP in vitro. Mutation analyses
      suggest that binding to rap30 and 'trans'-activation are two independent
      functions as a mutant which failed to interact with rap30 was still able to
      induce gene expression with wildtype efficiency. Moreover loss of transcriptional
      activity does not correlate with a loss of TBP binding suggesting that this
      association is not necessary for the N-terminal 'trans'-activating activity.
      Interestingly, aa 1-29 of Ad2 E1A binds also to rap30 indicating that this
      interaction might be a common feature of E1A proteins from different serotypes.

PMID- 9660076
TI  - Nucleotide sequences of the matrix protein gene of subacute sclerosing
      panencephalitis viruses compared with local contemporary isolates from patients
      with acute measles.
AB  - Measles viruses isolated from brain cells of patients with subacute sclerosing
      panencephalitis (SSPE) have numerous mutations, especially in the matrix protein
      (M) gene. To find whether the M genes of these SSPE viruses were mutated randomly
      or in a pattern, we sequenced this gene from three strains of defective measles
      virus isolated in Osaka, Japan. We could deduce the sequence of the possible
      progenitor measles virus for each patient by comparison of the isolate with
      measles viruses prevailing at roughly the same time and place as the primary
      infection. Biased hypermutation affected the M genes of all three SSPE viruses,
      although the molecular mechanisms for the mutations might be various.
      Replacements of U with C in the plus strand accounted for 76% of all mutations in
      two of the strains, but in the other strain, replacements of A with G accounted
      for 52% of the mutations, and the U residues were unchanged.

PMID- 9660077
TI  - Conference report. Strategies in virus-host relationships.

PMID- 9660078
TI  - The interaction between leptin and the hypothalamic-pituitary-thyroid axis.
AB  - The description of the adipose tissue hormone leptin has led to important
      discoveries. Leptin plays a role not only in the regulation of metabolic
      efficiency, energy expenditure, food intake and adiposity, but also contributes
      greatly to the adaptation of the organism to starvation. Much of the literature
      has focused on the physiologic roles of leptin-driven processes as diverse as
      feeding behavior, body weight, defense to starvation and reproduction. The
      following discussion summarizes knowledge that has accumulated regarding the
      interaction between leptin and the hypothalamic-pituitary-thyroid axis.

PMID- 9660079
TI  - Effect of dehydroepiandrosterone on brown adipose tissue and energy balance in
      mice.
AB  - In order to investigate the reported antiobesity action of dehydroepiandrosterone
      (DHEA), a complete energy balance was made on four groups of mice. Group A was
      fed the standard Purina diet, group B the same diet to which DHEA was added
      (0.3%), group C the Purina diet supplemented with palatable high fat food (meat
      spread), and group D the same diet as group C, to which DHEA was added. Food
      intake which was larger in groups C and D, was not altered by DHEA treatment.
      Body weight gain which was comparable for groups A and C, was significantly
      reduced in the two groups receiving DHEA. The resulting reduced food efficiency
      caused by DHEA was completely explained by body fat utilization. It was also
      found that the weight and the protein content of the interscapular brown adipose
      tissue (BAT) were increased by DHEA treatment suggesting, because of the great
      thermogenic capacity of this tissue in mice, that it may have been involved in
      causing the observed reduction in food efficiency. It is also proposed that the
      action of DHEA may be related to the activation of other tissues such as the
      liver and muscles. Further investigations are needed to verify this possibility.

PMID- 9660080
TI  - Vasoactive intestinal peptide stimulates rat adrenal glucocorticoid secretion,
      through an ACTH receptor-dependent activation of the adenylate cyclase signaling
      pathway.
AB  - Vasoactive intestinal peptide (VIP) concentration-dependently enhanced
      corticosterone and cyclic-AMP release by dispersed rat inner adrenocortical
      cells. A VIP-receptor antagonist and the ACTH-receptor antagonist corticotropin
      inhibiting peptide annulled both adrenocortical-cell responses to VIP, while the
      protein kinase (PKA) inhibitor H-89 blocked only corticosterone response.
      Collectively, these findings suggest that VIP stimulates glucocorticoid secretion
      of rat adrenals, through the aspecific activation of ACTH receptors coupled with
      the adenylate cyclase/PKA-dependent signaling pathway.

PMID- 9660081
TI  - Comparison between the effects of D-mannoheptulose and its hexaacetate ester upon
      D-glucose metabolism in rat erythrocytes.
AB  - At a 2.0 mM concentration, D-mannoheptulose hexaacetate, but not unesterified D
      mannoheptulose, inhibited the generation of radioactive acidic metabolites by rat
      erythrocytes exposed to D-[U-14C]glucose (8.3 mM). It is proposed that D
      mannoheptulose hexaacetate represents a valuable tool to interfere with the
      phosphorylation of D-glucose in cell types otherwise resistant to the heptose.

PMID- 9660082
TI  - Activities of aminopeptidases in a rat saline model of volume hypertension.
AB  - Aminopeptidase activity plays a role in the metabolism of several peptides that
      could be involved in blood pressure control. This activity has been implicated in
      the pathogenesis of hypertension, essentially in spontaneously hypertensive rats.
      However, few studies have examined aminopeptidase activities in animal models
      other than genetic hypertension. To analyze the aminopeptidase response to the
      specific conditions of the reduced renal mass saline model of arterial
      hypertension, aminopeptidase A activity (glutamyl- and aspartyl-aminopeptidase),
      aminopeptidase M activity (alanyl-aminopeptidase), aminopeptidase B activity
      (arginyl-aminopeptidase), pyroglutamyl-aminopeptidase and cystinyl-aminopeptidase
      were measured in the neurohypophysis, in the adrenal gland and in serum of this
      model of hypertension. In the neurohypophysis, there was a significant increase
      of soluble cystinyl-, alanyl-, arginyl-, pyroglutamyl- and membrane-bound
      aspartyl-aminopeptidase activities in hypertensive animals. In the adrenal gland,
      soluble cystinyl-, alanyl-, arginyl- and pyroglutamyl-aminopeptidase activities
      were also higher in hypertensive rats than in normotensive controls. No
      differences were found in serum levels of aminopeptidase activities between both
      groups of animals. A highly significant positive correlation between the
      neurohypophysis and the adrenal gland was observed for soluble cystinyl- and
      alanyl-aminopeptidase activities in the model of hypertension, whereas no
      correlation was observed in normotensive rats. Our results suggest that
      aminopeptidase activities could be involved in the regulatory response to the
      reduced renal mass hypertension and also suggest a coordinate response between
      the adrenal gland and the neurohypophysis, to the specific metabolic conditions
      of this model of hypertension.

PMID- 9660083
TI  - Pamidronate corrects the down-regulation of the renal parathyroid hormone
      (PTH)/PTH-related peptide (PTHrP) receptor mRNA in rats bearing Walker tumors.
AB  - Human hypercalcemia of malignancy (HHM) is generally due to the release into the
      circulation of parathyroid hormone-related peptide (PTHrP). PTHrP stimulates
      osteoclastic bone resorption and renal calcium reabsorption through the
      activation of a receptor similar to that of PTH (PTH-R). However, there is scarce
      information about the PTH-R regulation in the setting of the hypercalcemia. In
      the present study, we assessed the molecular basis of renal PTH-R regulation in
      Walker tumor-bearing rats either treated or not by a bisphosphonate, pamidronate.
      Twenty-seven 6-week-old rats were randomly divided into three experimental
      groups: WC- APD- (9 control rats), WC+ APD- (9 Walker tumor-bearing rats), and
      WC+ APD+ (9 Walker tumor-bearing rats receiving 15 mg/kg/day of sodium
      pamidronate every day for seven days). Pamidronate induced a significant decrease
      in the mean tumor weight (9.3+/-0.8 vs 6.3+/-0.6 g). Seven days after the
      subcutaneous implantation of the Walker cells, plasma total calcium was 10.8+/
      0.4, 16.8+/-0.6, and 12.9+/-0.6 mg/dl in WC- APD-, WC+ APD-, and WC+ APD+,
      respectively. Plasma PTHrP concentration was undetectable, 15.9+/-2.6, and 7.2+/
      1.4 pmol/l, respectively. Bone histomorphometric results showed high resorption
      in WC+ APD-, which returned below the basal level of the WC- APD- with
      pamidronate treatment. Densitometric analysis of Northern blots revealed that the
      renal PTH-R mRNA expression in WC+ WPD- rats was a quarter of the levels in the
      WC- APD- and WC+ APD+ groups. WC+ APD- also had a decreased PTH-stimulated cAMP
      production in renal membranes. The PTH-R was expressed in the Walker tumor and it
      was not modified by pamidronate treatment. In conclusion, the expression of PTH-R
      receptor mRNA is significantly reduced in the kidney of rats bearing Walker
      carcinoma tumor. Its regulation is tissue-specific: pamidronate, which partially
      corrected the hypercalcemia and elevated circulating PTHrP, normalized the PTH-R
      mRNA expression in the kidney but not in the tumor.

PMID- 9660084
TI  - Increased release of IAPP in response to long-term high fat intake in mice.
AB  - In the present study, mice were fed high-fat diet or standard animal chow during
      6 months. Animals fed high-fat diet showed a 4.5-fold increase in the fasting
      plasma IAPP levels compared to animals fed standard chow. No significant change
      in plasma insulin levels occurred between the groups. These differences in
      hormone response result in a change of the molar ratio between IAPP and insulin
      in the group fed high-fat diet. An increased IAPP to insulin molar ratio might be
      important in the pathogenesis of islet amyloid in man.

PMID- 9660085
TI  - Acute hyperleptinemia does not modify insulin sensitivity in vivo in the rat.
AB  - Insulin resistance is associated with hyperleptinemia, whilst exposure of
      hepatoma cells and isolated adipocytes to high concentrations of leptin has been
      demonstrated to result in attenuated insulin response and a reduced suppression
      of gluconeogenesis. To determine the acute metabolic effects of hyperleptinemia,
      we measured whole body glucose uptake (WBU) and hepatic glucose production rate
      (HGP) in rats using the euglycemic hyperinsulinemic clamping technique.
      Anesthetised male rats received recombinant murine leptin (1 microg/min) or
      vehicle into the jugular vein for 90 min. After 30 min of leptin infusion,
      insulin was infused to a level of 70 microU/ml and a variable-rate glucose
      infusion was adjusted to maintain blood glucose levels to 4-4.5 mmol/l. Glucose
      infusion rates during clamping were not different between leptin-infused and
      control rats, and there were no significant effects on the HPR or WBU measured
      using [6-(3)H]glucose under basal or clamped conditions. In summary, our data
      demonstrate that acute hyperleptinemia in normal weight Wistar rats does not
      appear to reduce insulin sensitivity, in vivo, or to affect HPR under clamp
      conditions.

PMID- 9660086
TI  - The influence of ovariectomy on ob gene expression in rats.
AB  - Ovarian steroid hormones exert major influences on eating behaviour and body
      weight regulation of female rats. Ovariectomy (OVX) results in an increase in
      food intake and a concomitant increase in body weight, while estradiol (E2)
      replacement reverses these effects. In this study, we examined the influence of
      OVX on obese (ob) gene expression in rat adipose tissues and serum leptin
      concentration. Female Wistar rats, 10 weeks old, were divided into three groups:
      sham-operated control rats receiving corn oil (group 1, n = 4), ovariectomized
      rats receiving corn oil (group 2, n = 5), and ovariectomized rats receiving
      17beta-E2 (10 microg/kg/day) replacement (group 3, n = 4). After 4 weeks, the
      rats and food consumption were weighed and serum E2 and leptin levels were
      measured by radioimmunoassays. Furthermore, the expression levels of ob mRNA
      obtained from the bilateral perimetric fat pads were estimated by Northern blot
      analysis. The mean weight and food consumption in group 2 were significantly (p <
      0.01) heavier than those in group 1. But there were no significant differences
      between group 1 and group 3. The expression levels of ob mRNA in group 2 were
      lower than those in group 1, however, the levels of group 3 were restored to the
      level of group 1. On the other hand, no significant differences among the 3
      groups as to serum levels of leptin were observed. The data herein clearly
      indicate that ovarian steroid hormones may be one of the factors involved in the
      regulation of ob gene.

PMID- 9660087
TI  - Effects of gonadotropin and testosterone treatments on plasma leptin levels in
      male patients with idiopathic hypogonadotropic hypogonadism and Klinefelter's
      syndrome.
AB  - Since little is known about the effects of gonadotropin and testosterone
      treatment on leptin levels in male hypogonadism, we determined fasting plasma
      leptin levels before and 3 months after treatment in 21 patients with idiopathic
      hypogonadotropic hypogonadism (IHH), 16 patients with Klinefelter's syndrome and
      20 male controls. Patients with IHH were treated with hCG/human menopausal
      gonadotropin, whereas patients with Klinefelter's syndrome received T treatment.
      Plasma leptin levels were measured by an RIA with a sensitivity of 0.5 microg/L.
      Mean leptin levels in patients with IHH before treatment (9.23+/-4.09 microg/L)
      were not significantly different from those in patients with Klinefelter's
      syndrome (7.29+/-5.05 microg/L; z=-1.41; P=0.15). Leptin levels in both IHH and
      Klinefelter's syndrome groups were, however, significantly higher than in the
      normal men (3.91+/-1.67 microg/L) (P<0.001 and P<0.01, respectively). Mean leptin
      levels did not change significantly 3 months after the initiation of gonadotropin
      (11.6+/-6.44 microg/L) or T (8.32+/-5.17 microg/L) treatment in either IHH or
      Klinefelter's syndrome. Our study demonstrated that mean plasma leptin levels are
      not influenced by short-term gonadotropin or T treatment in male hypogonadism.

PMID- 9660088
TI  - Serum leptin and body weight in females with anorexia and bulimia nervosa.
AB  - In this study we hypothesized that there is a correlation between serum leptin
      levels and body mass indices within patients with anorexia nervosa or bulimia
      nervosa during a twelve weeks' course of in-patient treatment. We evaluated
      leptin levels weekly in female in-patients with anorexia (n = 17) or bulimia
      nervosa (n = 18). Only patients with anorexia nervosa were therapeutically
      encouraged to gain weight throughout the treatment episode. For the whole cohort,
      body mass indices and serum leptin levels were highly correlated upon admission
      (r = 0.89, p < 0.001). The median intra-individual correlation in the anorexia
      group was higher than in the bulimia group (0.63 and 0.39, respectively). The
      intra-individual correlations were higher in those anorexia nervosa patients who
      showed increments of their body mass index within the observation span. This
      dynamic aspect is important specifically in patients with anorexia nervosa during
      therapeutically induced weight gain.

PMID- 9660089
TI  - Lack of association between the insertion/deletion polymorphism of the
      angiotensin-converting-enzyme gene and diabetic nephropathy in IDDM patients.
AB  - The insertion/deletion (I/D) polymorphism of the angiotensin-converting-enzyme
      (ACE) gene has been reported to be associated with diabetic nephropathy in IDDM.
      We studied the relationship between this polymorphism and diabetic nephropathy in
      210 IDDM patients. Their DNA was analyzed by polymerase chain reaction to type
      for the presence (I) or absence (D) of the 287 bp fragment in intron 16 of the
      ACE gene. The relative frequency of the different genotypes was 33.8% (DD), 43.8%
      (ID), and 22.4% (II). There were no significant differences between the genotypes
      in age, body-mass-index, blood pressure, plasma total cholesterol and
      triglycerides. The prevalence of microalbuminuria or nephropathy was 23.9% in the
      DD, 16.3% in the ID, and 17% in the II genotypes. The higher percentage of
      microalbuminuria or nephropathy in the DD genotypes was due to an increasing
      frequency of DD genotypes in the IDDM patients with long diabetes duration. After
      matching for diabetic retinopathy, gender, and diabetes duration, there was no
      association between the ACEI/D polymorphism and diabetic nephropathy. In
      conclusion, these results suggest that the ACE DD genotype cannot be regarded as
      a risk factor for diabetic nephropathy, but may even be associated with diabetes
      duration and thus longevity in IDDM patients.

PMID- 9660090
TI  - Effects of hypophosphatemia on glucose tolerance and insulin secretion.
AB  - Phosphate is an active participant in energy metabolism, and its deficiency has
      been associated with changes in insulin sensitivity and glucose tolerance. In the
      present study, we have investigated insulin secretion and glucose tolerance in
      individuals with moderate and acute phosphate deprivation and in patients with
      chronic hypophosphatemia. The individuals with dietary phosphate deprivation,
      evidenced by a significant reduction in phosphaturia from 232.3 +/- 37.1 to 56.8
      +/- 23.9 mmol/24 hours, but with normal serum levels of inorganic phosphorus,
      presented circulating glucose and insulin levels similar to those of the pre
      dietary period during the oral and intravenous glucose tolerance tests. In
      contrast, patients with chronic hypophosphatemia (inorganic phosphorus < 0.65
      mmol/l) presented in hyperinsulinemia during the postabsorptive state and during
      the early and late phases of insulin secretion after the oral and intravenous
      glucose stimulus. The physiological response of a fall in serum phosphate after
      glucose administration observed in individuals with chronic hypophosphatemia was
      similar to that of normal individuals. The presence of hyperinsulinemia both
      basally and after glucose stimulation, with normal glycemia, in phosphate
      depleted individuals suggests that this condition is associated with reduced
      insulin sensitivity. However, severe phosphate deprivation is necessary for the
      manifestation of this undesirable association. The deviation of phosphate to the
      intracellular medium occurring after glucose administration in hypophosphatemic
      individuals is similar to that of normal individuals and explains the occurrence
      of severe hypophosphatemia in malnourished hypophosphatemic individuals when
      submitted to parenteral refeeding.

PMID- 9660091
TI  - In vitro and in vivo characterization of (+)-3-[11C]cyano-dizocilpine.
AB  - (+)-3-[11C]Cyano-5-methyl-10,11 -dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine
      ([11C]MKC) was successfully synthesized as a potential radiotracer for PET
      studies on the NMDA receptor channel complex. In vitro binding properties of
      [11C]MKC were investigated with newly developed techniques for efficient
      evaluation of 11C-labeled compounds. The association curve of [11C]MKC binding in
      rat forebrain membranes showed that the specific binding reached an equilibrium
      within 30 min. Specific binding was saturable with affinity constant KD=8.2+/
      0.4nM and Bmax=1.62+/-0.04 pmol/mg protein with glutamate and glycine included in
      the incubation medium. The binding of [11C]MKC was decreased by extensive washing
      of the membrane preparation. (+)- and (-)-Dizocilpine, 3-cyano-dizocilpine, and
      ketamine inhibited the specific binding of [11C]MKC with IC50 values of 37.3,
      445.0, 65.8nM and 3.91 microM, respectively. High specific binding in in vitro
      autoradiography was distributed predominantly in telencephalic regions (the
      hippocampus, cerebral cortex, and striatum) followed by thalamus. PET studies
      using rhesus monkeys under anesthesia showed high uptake of [11C]MKC in the
      temporoparietal and frontal cerebral cortices, striatum, and thalamic regions,
      although it is problematic to verify the specific binding in vivo by PET.

PMID- 9660092
TI  - Effect of 5-fluoroindole-2-carboxylic acid (an antagonist of the NMDA receptor
      associated glycine site) on the anticonvulsive activity of conventional
      antiepileptic drugs.
AB  - 5-Fluoroindole-2-carboxylic acid, an antagonist of the glycine site within the
      NMDA receptor complex, administered intraperitoneally in doses of 150 and 200
      mg/kg, 120 min before electroconvulsions, significantly raised the convulsive
      threshold from 6.8 to 7.9 and 8.3 mA, respectively. At lower doses, it did not
      influence the threshold. However, lethality was observed 24h after administration
      of the threshold-elevating doses of this glycine site antagonist. 5-Fluoroindole
      2-carboxylic acid (100 mg/kg), applied together with carbamazepine, valproate or
      phenobarbital, significantly reduced their ED50 values against maximal
      electroshock - from 13.9 to 7.5 mg/kg, from 291 to 242 mg/kg, and from 18.6 to
      11.1 mg/kg, respectively. At the dose of 50 mg/kg, it also potentiated the
      protective activity of carbamazepine. However, 5-fluoroindole-2-carboxylic acid,
      up to 100 mg/kg, did not affect the anti-convulsive activity of
      diphenylhydantoin. When applied at doses equal to their ED50 values against
      maximal electroshock-induced convulsions, carbamazepine (13.9 mg/kg),
      phenobarbital (18.6 mg/kg) and valproate (291 mg/kg) did not affect the motor
      performance of mice in the chimney test. 5-Fluoroindole-2-carboxylic acid (100
      mg/kg produced a significant motor impairment, at 50 mg/kg it did not affect the
      motor performance. The combined treatment of 5-fluoroindole-2-carboxylic acid
      (100 mg/kg) with carbamazepine, phenobarbital or valproate, providing a 50%
      protection against maximal electroshock, resulted in motor impairment. Only the
      combination of 5-fluoroindole-2-carboxylic acid (50 mg/kg) with carbamazepine
      (8.6 mg/kg) did not significantly influence this parameter. Almost all of the
      antiepileptic drugs studied, when administered at doses equal to their ED50
      values against maximal electroshock, did not influence retention in the passive
      avoidance task, which is a measure of long-term memory. Only valproate (291
      mg/kg) worsened long-term memory. The combined treatment of 5-fluoroindole-2
      carboxylic acid (100 mg/kg) with carbamazepine or phenobarbital, providing a 50%
      protection against maximal electroshock, did not affect the retention. The
      combination of 5-fluoroindole-2-carboxylic acid (100 mg/kg) with valproate (242
      mg/kg) caused a significant impairment of long-term memory and mortality of 50%
      of animals 24h following the administration. The results suggest that the
      blockade of the strychnine-insensitive glycine site may lead to an enhancement of
      the protective activity of some conventional antiepileptic drugs, which is
      associated with pronounced side-effects and lethality in some cases.

PMID- 9660093
TI  - Effects of kynurenine metabolites on the electrocorticographic activity in the
      rat.
AB  - We examined the effects of kynurenine metabolites administered into the right
      cerebroventricle (1 micromol) on the electrocorticogram (ECoG) of rats to
      establish the role of kynurenines on brain function. Kynurenine, anthranilic
      acid, quinaldic acid, xanthurenic acid or 8-hydroxyquinaldic acid showed no
      effect on ECoG throughout the recording period of 4 hours. 3-Hydroxykynurenine
      had a transient suppressive effect on the ECoG, while kynurenic acid caused a
      slight suppression of ECoG activity. 3-Hydroxyanthranilic acid (3-OH-An), a
      metabolite of 3-hydroxykynurenine, induced spike discharges with a long latency
      (60-230 min). 3-OH-An is thought to be metabolized to o-aminophenol, 3
      methoxyanthranilic acid, quinolinic acid, 2-ketoadipic acid and picolinic acid.
      Among 3-OH-An metabolites, only o-aminophenol induced spike discharges several
      minutes after administration, lasting for 60 min. On the other hand, quinolinic
      acid suppressed ECoG, though 3-methoxyanthranilic acid, 2-ketoadipic acid and
      picolinic acid had no effects on ECoG. These electrocorticographic findings
      suggest that 3-OH-An may induce spike discharges after it is metabolized in the
      brain to o-aminophenol.

PMID- 9660094
TI  - Tolbutamide blocks postsynaptic but not presynaptic effects of adenosine on
      hippocampal CA1 neurones.
AB  - Extracellular recording in the CA1 pyramidal cell layer of rat hippocampal slices
      was used to examine the effect of the ATP-sensitive potassium channel blocker
      tolbutamide and the channel opener levcromakalim on responses to adenosine.
      Tolbutamide 1 mM blocked the inhibitory effect of adenosine on the size of
      orthodromic population spikes but had no effect on the inhibitory action of
      adenosine on field EPSPs. Tolbutamide also blocked the suppression by adenosine
      of repetitive antidromic spikes induced in calcium-free media with high magnesium
      but did not prevent the effects of baclofen. Levcromakalim 100 microM potentiated
      inhibitory effect of adenosine, but not baclofen, on orthodromic population
      spikes. The results show that at postsynaptic, but not presynaptic, sites
      adenosine may activate an ATP-sensitive potassium channel.

PMID- 9660095
TI  - Melatonin inhibits oxytocin response to insulin-induced hypoglycemia, but not to
      angiotensin II in normal men.
AB  - In order to establish whether melatonin alters basal and/or stimulated oxytocin
      secretion, 18 normal men were treated (p.o.) with 6 or 12 mg melatonin or placebo
      in basal conditions (N-6 subjects) or concomitantly to the administration of
      insulin (O.15 IU/kg body weight in an i.v. bolus) (N-6 subjects) or angiotensin
      II (increasing doses of 4, 8 and 16 ng/kg/min, at intervals of 20 min). The
      administration of 6 or 12 mg melatonin did not change basal and angiotensin II
      stimulated oxytocin secretion. In contrast, the oxytocin response to insulin
      induced hypoglycemia was significantly reduced by melatonin treatment. In fact,
      the mean peak oxytocin response to hypoglycemia was 2.2 times higher than
      baseline in the absence of melatonin, whereas it was 1.6 times higher than basal
      value after administration of 6 or 12 mg melatonin. These data indicate an
      involvement of melatonin in the regulation of the oxytocin response to
      hypoglycemia in normal men. The lack of effects of melatonin on basal and
      angiotensin II-stimulated oxytocin secretion argues against the possibility that
      melatonin exerts an overall modulatory role on oxytocin secretion in humans.

PMID- 9660096
TI  - In vivo occupation of dopamine D1, D2 and serotonin2A receptors by novel
      antipsychotic drug, SM-9018 and its metabolite, in rat brain.
AB  - In vivo occupation of dopamine D1, D2 and serotonin (5-HT)2A receptors by a novel
      antipsychotic drug, SM-9018 (perospirone hydrochloride; cis-N- [4- [4- (1,2
      benzisothiazol-3-yl)- 1-piperazinyl]butyl]cyclohexane-1,2-dicarboximide
      monohydrochloride) and its major metabolite (ID-15036; N-[4-[4-(1,2
      benzisothiazol-3-yl)-1-piperazinyl]butyl]-1-hydroxy-1 , 2
      cyclohexanedicarboximide) was measured in rat brain using N-ethoxycarbonyl-2
      ethoxy-1,2-dihydroquinoline (EEDQ), an irreversible antagonist, at these receptor
      sites. SM-9018 and its metabolite, ID-15036, dose-dependently reversed EEDQ
      induced 5-HT2A and D2 receptor inactivation, but not D1 receptor inactivation. At
      lower doses (0.1 mg/kg i.p.), SM-9018 showed a preferential occupation of the 5
      HT2A receptors, with only a small effect on the D2 receptors; while at higher
      doses (1.0 and 5.0 mg/kg i.p.), it was nearly equipotent in its occupation of
      both the D2 (77.8%) and the 5-HT2A receptors (78.6%). On the other hand, ID-15036
      was more potent in occupying the 5-HT2A than the D2 receptors even at higher
      doses (1.0 and 5.0 mg/kg i.p.). We previously reported that atypical
      antipsychotic drugs, such as clozapine, were characterized by a high occupancy of
      the 5-HT2A receptors, with a low or minimum occupancy of the D2 receptors in
      vivo. The present study suggests that SM-9018 and its metabolite ID-15036 show a
      preferential tendency to occupy 5-HT2A receptors, and that the clozapine-like
      atypical properties of SM-9018 may be due to some pharmacological action of both
      the SM-9018 itself and its metabolite, ID-15063.

PMID- 9660097
TI  - Involvement of endogenous nitric oxide signalling system in brain muscarinic
      acetylcholine receptor activation.
AB  - Biochemical signalling events coupled to muscarinic cholinergic receptors
      (mAChR), specifically those related to nitric oxide (NO) production, were studied
      on rat cerebral frontal cortex. The mAChR agonist carbachol was found to exert a
      specific biphasic action on NO synthase (NOS) activity: low doses ranging between
      10(-9) M to 10(-7) M lead to NOS activation while higher doses (>10(-6) M)
      inhibited enzymatic activity. Carbachol stimulatory action was blunted by agents
      that interfere with calcium-calmodulin while a protein kinase (PKC) inhibitor,
      staurosporine was able to abrogate the inhibitory effect. Moreover, PKC activity
      showed maximum translocation to cerebral frontal cortex membranes with carbachol
      concentrations that inhibited NO production. Products from phosphoinosite (PI)
      hydrolysis are involved in these actions as carbachol was found to increase PI
      turnover in a dose dependent manner. These results would serve as an example of
      cross-talk between both enzymatic pathways.

PMID- 9660098
TI  - 5-Hydroxyindoles compounds and nitric oxide voltammetric detection in the rat
      brain: changes occurring throughout the sleep-wake cycle.
AB  - The release of serotonin may occur throughout the sleep-wake cycle according to 2
      different modalities: - by the axonal nerve endings during waking; - by the
      dendrites and/or the soma of the nucleus raphe dorsalis (nRD) during sleep.
      Neuronal nitric oxide (NO), synthesised by constitutive NO synthase (NOS), is
      colocalized with neurotransmitters such as GABA, acetylcholine, somatostatin,
      serotonin, etc. In order to evaluate its modalities of release throughout the rat
      sleep-wake cycle, a sensor allowing its specific detection in freely moving
      animals was prepared. In the cortex, the highest NO signal occurs during the
      waking state (W=100%) versus slow wave sleep (SWS=-6%) and paradoxical sleep (PS=
      9%). The mild variations observed might reflect a mean of the individual sleep
      wake cycle variations attached to each NO source (GABAergic interneurons,
      cholinergic and serotoninergic axonal nerve endings, etc.).

PMID- 9660099
TI  - Retrospective application of a set of clinical diagnostic criteria for the
      diagnosis of multiple system atrophy.
AB  - We estimated the accuracy of a modified commonly used set of clinical diagnostic
      criteria for the diagnosis of multiple system atrophy (MSA) by retrospectively
      applying the criteria to the features recorded by six neurologists who had
      evaluated 105 autopsy-confirmed cases (16 MSA and 89 non-MSA disorders). Cases
      were abstracted from the records of the patients' first visit to an academic
      center, and were presented as clinical vignettes to six neurologists, each of
      whom recorded the main clinical features of the presented clinical vignette on a
      standardized form. Sensitivity and positive predictive values were chosen as
      validity outcome measures and were calculated by comparing the applied diagnostic
      criteria to the neuropathologic information. Of note, most MSA patients in this
      study (mainly those with Shy-Drager type) had not received levodopa therapy since
      the primary neurologists often had not perceived a need to administer this
      treatment. The validity of the retrospectively applied criteria for the diagnosis
      of possible MSA (sensitivity: median, 53%, range, 50-69%; positive predictive
      value: 30%, 28-39%) and probable MSA (sensitivity: 44%, 31-60%; positive
      predictive value: 68%, 54-80%) at the first visit was suboptimal. The best, still
      not perfect, accuracy for this set of diagnostic criteria was obtained when six
      out of eight features (sporadic adult onset, dysautonomia, parkinsonism,
      pyramidal signs, cerebellar signs, no levodopa response, no cognitive
      dysfunction, or no downward gaze supranuclear palsy) were present (median
      sensitivity, 59%; range, 50-75%; positive predictive value: 67%, 53-83%). This is
      the first study to validate criteria for the clinical diagnosis of MSA. Our data
      suggest that it is difficult to achieve an early and accurate clinical diagnosis
      of this disorder. The probability of correctly diagnosing MSA increases when at
      least six features of this modified set of criteria are present or when requiring
      the set for probable MSA.

PMID- 9660100
TI  - Bradykinesia and hypokinesia in Parkinson's disease: what's in a name?
AB  - Because in the literature bradykinesia and hypokinesia are frequently confounded,
      we assessed the relation between these two fundamental aspects of altered
      movement and the influence of disease severity on these measures in 41 patients
      with Parkinson's disease (PD) and 24 age-matched healthy controls. Bradykinesia
      was measured with a test microcomputer interfaced with a response-board.
      Hypokinesia was assessed by activity monitoring at home over a period of 5
      successive days. For each subject the choice reaction time and measures
      reflecting bradykinesia (tap rate, movement time) and hypokinesia (movement
      index, duration of immobility periods) were calculated. Patients with PD had a
      normal choice reaction time and a significantly impaired execution of voluntary
      movement and reduced amount of movement over time. Bradykinesia was clearly
      present in the less affected patients with PD, and worsened as the disease
      severity increased. Hypokinesia, however, emerged prominently only in the more
      affected patients. There was a striking lack of relation between the measures
      that reflect bradykinesia and hypokinesia. The use of levodopa or dopamine
      agonists did not confound these findings. Our findings show the very different
      character and course of two tiers of altered movement in patients with PD and
      question the causative mechanisms of both motor features in PD. A more precise
      use of the terms brady- and hypokinesia is a prerequisite for future studies that
      attempt to provide insight in the causative mechanisms of both motor features.

PMID- 9660101
TI  - Plasma levels of R- and S-salsolinol are not increased in "de-novo" Parkinsonian
      patients.
AB  - An augmented synthesis of tetrahydroisoquinolines, such as salsolinol (SAL) or an
      increased N-methylation of these compounds has been addressed by various
      investigators as putative pathophysiologic mechanisms in Parkinson's disease
      (PD). Aim of this study was (1) to investigate putative relations between plasma
      levels of dopamine and R- and S-enantiomers of SAL and (2) whether these
      metabolic precursors of the neurotoxic N-methylated-SAL (NMSAL) are elevated in
      untreated "de-novo" Parkinsonian patients compared to age- and sex-matched
      healthy controls. Plasma levels of R- and S-SAL and dopamine did not
      significantly (R-SAL: p=0.61, S-SAL: p=0.51, dopamine: p=0.84) differ in both
      groups. Parkinsonian patients' R-SAL plasma levels were inversely related to
      intensity (p=0.03, r =-0.42) and duration of PD (p=0.03, r=-0.43) in contrast to
      S-SAL and dopamine. Dopamine levels were not associated to R-SAL (p=0.88,
      r2=0.0008) and S-SAL (p=0.088, r2=0.12) neither in Parkinsonian patients nor in
      controls. We conclude, that an upregulation of N-methylation of
      tetrahydroisoquinolines takes place in PD by enzymes such as neutral N
      methyltransferase specific for R-SAL. The activity of this enzyme has been found
      elevated in parkinsonian lymphocytes. This increased N-methylation by the N
      methyltransferase specific for R-SAL leads to the known augmented levels of
      neurotoxic R-NMSAL in Parkinsonian patients compared to controls in the cenral
      nervous system especially in the beginning of PD.

PMID- 9660102
TI  - Sertraline induced parkinsonism. A case report and an in-vivo study of the effect
      of sertraline on dopamine metabolism.
AB  - We report a patient with a parkinsonian syndrome induced by sertraline (Zoloft),
      an SSRI antidepressant, whose symptoms resolved after the drug was discontinued.
      This case prompted us to investigate the effect of sertraline on dopamine
      metabolism in animals. Sertraline (30 mg/kg, i.p.) or placebo (vehicle) was
      administered to two groups of six normal, anesthetized rats and using cerebral
      microdyalisis extracellular striatal levels of dopamine, the dopamine metabolites
      (HVA and DOPAC), as well as the serotonin metabolite 5-HIIA were monitored. In
      animals pre-treated with sertraline, DOPAC, HVA, and 5-HIAA levels were
      significantly decreased compared to control animals (p < 0.01). These data
      indicate that sertraline has an effect on dopamine metabolism, which may alter
      function in the striatum and induce a parkinsonian syndrome.

PMID- 9660103
TI  - BDNF and TrkB expression in intrastriatal ventral mesencephalic grafts in a rat
      model of Parkinson's disease.
AB  - We investigated the expression of BDNF and its high affinity receptor trkB in
      fetal dopaminergic grafts in a rat model of Parkinson's disease. Grafts were
      allowed to differentiate for 7, 14, 28, or 56 days, respectively and were
      analyzed immunocytochemically thereafter with antibodies directed against
      tyrosine hydroxylase, BDNF and trkB. At all time points investigated, grafts
      contained tyrosine hydroxylase immunoreactive neurons. Immature grafts (7 days)
      displayed no immunoreactivity for BDNF which was restricted to glial cells at the
      graft-host interface. After longer differentiation periods BDNF-immunoreactivity
      was detectable in neurons and astrocytes within the grafts. No trkB
      immunoreactivity was found in immature grafts but a strong signal for trkB
      emerged in grafted neurons older than 14 days whereas glial cells remained
      unlabeled at all time points investigated. Expression of BDNF and trkB in grafted
      neurons and of BDNF in surrounding glial cells suggests an autocrine or paracrine
      action of BDNF on dopaminergic neurons possibly mediated by activated glia.

PMID- 9660104
TI  - Pergolide: treatment of choice in Restless Legs Syndrome (RLS) and Nocturnal
      Myoclonus Syndrome (NMS). Longterm follow up on pergolide. Short communication.
AB  - Pergolide has proven significantly superior to L-dopa plus peripheral
      decarboxylase inhibitor in short-term therapy of RLS/NMS. We now first present
      long-term follow-up sleep data showing its lastingly good effects after averagely
      517 treatment days.

PMID- 9660105
TI  - Neurotransmitter amino acids in cerebrospinal fluid of patients with Alzheimer's
      disease.
AB  - We measured the CSF and plasma levels of glutamate, glutamine, aspartate (only in
      plasma), asparagine, glutamine, glycine and GABA in 37 patients with Alzheimer's
      disease and in 32 matched controls. We used an ion-exchange chromatography
      method. When compared to controls, AD patients had higher CSF glutamate and
      glycine levels, higher plasma levels of aspartate and glycine, and lower plasma
      levels of asparagine and GABA. When expressed relative to CSF proteins, CSF
      levels of glutamate and glycine remained higher, and CSF asparagine levels were
      lower in AD patients than in controls. The CSF levels of the amino acids measured
      were not correlated with the clinical features of AD with the exception of plasma
      GABA levels with duration of the disease. Our results might suggest a possible
      pathogenetic role of neurotransmitter amino acids in AD.

PMID- 9660106
TI  - Cerebrospinal fluid levels of non-neurotransmitter amino acids in patients with
      Alzheimer's disease.
AB  - We measured the CSF levels of 21 and the plasma levels of 24 amino acids in 37
      patients with Alzheimer's disease (AD) and in 32 matched controls. We used an ion
      exchange chromatography method. When compared with controls, AD patients had
      lower CSF levels of phosphoserine, citrulline, alfa-aminobutyric acid,
      methionine, and ethanolamine; and higher CSF levels of threonine, serine, lysine,
      histidine and arginine. However, when expressed relative to CSF protein, CSF
      levels of serine, lysine, histidine, and arginine, were normal. AD patients had
      higher plasma levels of phosphoserine, threonine, citrulline, hydroxyproline, and
      proline; and lower plasma levels of alfa-aminobutyric acid, methionine, leucine
      and ethanolamine. The CSF/plasma ratios of phosphoserine, serine, citrulline,
      alfa-aminobutyric acid and arginine were significantly lower in AD patients than
      those of controls. CSF amino acid levels were not related with the duration and
      severity of the disease.

PMID- 9660107
TI  - Abnormal amino acid metabolism in patients with early stage Alzheimer dementia.
AB  - Plasma levels of several amino acids were studied in 14 patients with early stage
      probable Alzheimer's disease (AD) and 17 age-matched controls. In the AD patients
      a possible relationship between amino acid levels and behavioural symptomatology
      was also investigated. We found significantly reduced levels of tryptophan and
      methionine in plasma samples from the AD patients compared to the control
      subjects. Moreover, plasma tyrosine/large neutral amino acids (LNAA) ratio and
      the ratio of plasma taurine and the product of the plasma levels of methionine
      and serine (TSM-ratio) were significantly increased in the AD patients in
      comparison with the controls. However, no difference was found in plasma
      tryptophan/LNAA ratio and in homocysteine levels between both groups. Concerning
      the behavioural symptomatology no significant correlation was found between the
      Reisberg Behave AD scale and plasma amino acid levels or ratios. The reported
      findings suggest that abnormal amino acid metabolism is present in the early
      stages of AD. We hypothesize that this abnormality could play a role in the
      pathogenesis of behavioural changes occurring in later stages of AD.

PMID- 9660108
TI  - Antiglutamatergic therapy in Alzheimer's disease--effects of lamotrigine. Short
      communication.
AB  - It has been proposed that excitotoxic damage by glutamatergic hyperactivity is
      responsible for neurodegeneration in Alzheimer's disease. Lamotrigine (LTG)
      inhibits presynaptic glutamate release and is considered to be effective in
      treatment of other neurodegenerative disorders by its cerebroprotective
      properties. We used LTG in 11 patients with the diagnosis of probable Alzheimer's
      disease. 300 mg/day administration of LTG improved word recognition, naming and
      depressed mood on Alzheimer Disease Assessment Scale (ADAS).

PMID- 9660109
TI  - Abnormal persistence of cerebellar serotonin-1A receptors in schizophrenia
      suggests failure to regress in neonates.
AB  - This study investigated the neurodevelopmental basis of schizophrenia by
      examining an early transient population of serotonin-1A (5-HT1A) receptors using
      quantitative [3H]8-OH-DPAT autoradiography on sections of frozen postmortem
      cerebellum. Production of an ontogenetic map showed that human neonatal
      cerebellum acquired dense 5-HT1A receptors, most of which were eliminated by
      early childhood. Autoradiographic measurements on cerebellar vermis from 16
      control adult subjects confirmed sparse 5-HT1A receptor binding. The data show a
      persistence of some vermal 5-HT1A receptors in brains from 19 adults with chronic
      schizophrenia in whom there may have been a slowed or arrested postnatal
      regression of vermal 5-HT1A receptors. Alternatively, some 5-HT1A receptors may
      have been re-expressed prior to, or subsequent to, the onset of the disease
      symptoms. The findings are not obviously explained by drug treatment and there
      are no data to explain how neuroleptics might promote expression of cerebellar 5
      HT1A receptors. We propose that the study has identified a neurotransmitter
      receptor population which, in schizophrenia, undergoes misdirected reshaping
      during brain development. The findings support neurodevelopmental hypotheses of
      the disease.

PMID- 9660110
TI  - Adult treatment with haloperidol increases dentate granule cell proliferation in
      the gerbil hippocampus.
AB  - Male gerbils were bred and reared grouped under enriched semi-natural
      environmental conditions. The objective of the present study was to examine the
      influence of an acute treatment with the neuroleptic haloperidol on adult granule
      cell neurogenesis in the hippocampus. For that purpose, at the age of postnatal
      day 90 adult animals received 4 challenges of either haloperidol (5 mg/kg, i.p.)
      or saline. Proliferation of granule cells was identified by in-vivo labeling with
      5-bromo-2'-desoxyuridine (BrdU) which was applied 1 hour after the final dose of
      haloperidol. BrdU-labeled granule cell nuclei were identified in consecutive
      horizontal slices along the mid-septotemporal axis of the hippocampus and light
      microscopically quantified 7 days after the BrdU-labeling. It was found that in
      both saline- and haloperidol-treated animals there was a highly significant
      spatial septotemporal gradient in granular cell proliferation with numbers of
      BrdU-labeled cells gradually declining from the septal towards the temporal pole.
      The acute treatment with haloperidol stimulated granule cell proliferation by
      about 75% and the septotemporal gradient of mitotic activity became significantly
      enhanced. The present results are discussed with regard to known factors
      regulating cell proliferation in the hippocampus and other cell systems.

PMID- 9660111
TI  - Repeated trimipramine induces dopamine D2/D3 and alpha1-adrenergic up-regulation.
AB  - Trimipramine (TRI), which shows a clinical antidepressant activity, is chemically
      related to imipramine but does not inhibit the reuptake of noradrenaline and 5
      hydroxytryptamine, nor does it induce beta-adrenergic down-regulation. The
      mechanism of its antidepressant activity is still unknown. The aim of the present
      study was to find out whether TRI given repeatedly was able to induce adaptive
      changes in the dopaminergic and alpha1-adrenergic systems, demonstrated by us
      previously for various antidepressants. TRI was given to male Wistar rats and
      male Albino Swiss mice perorally twice daily for 14 days. In the acute experiment
      TRI (given i.p.) does not antagonize the reserpine hypothermia in mice and does
      not potentiate the 5-hydroxytryptophan head twitches in rats. TRI given
      repeatedly to rats increases the locomotor hyperactivity induced by d
      amphetamine, quinpirole and (+)-7-hydroxy-dipropyloaminotetralin (dopamine D2 and
      D3 effects). The stereotypies induced by d-amphetamine or apomorphine are not
      potentiated by TRI. It increases the behaviour stimulation evoked by
      phenylephrine (given intraventricularly) in rats, evaluated in the open field
      test as well as the aggressiveness evoked by clonidine in mice, both these
      effects being mediated by an alpha1-adrenergic receptor. It may be concluded
      that, like other tricyclic antidepressants studied previously, TRI given
      repeatedly increases the responsiveness of brain dopamine D2 and D3 (locomotor
      activity but not stereotypy) as well as alpha1-adrenergic receptors to their
      agonists. A question arises whether the reuptake inhibition is of any importance
      to the adaptive changes induced by repeated antidepressants, suggested to be
      responsible for the antidepressant activity.

PMID- 9660112
TI  - Intradiploic arachnoid cyst of the posterior fossa.

PMID- 9660113
TI  - Magnetic resonance imaging of normal and pathologic fetal brain.
AB  - A total of 78 pregnant patients who had previously been studied by ultrasound
      (US) underwent magnetic resonance (MRI) because of suspected fetal abnormality.
      The first 20 cases were performed using fetal curarization. Even in the 27 cases
      in which the MR examination concerned other body regions, a brain study was
      always performed to analyze the normal anatomy at different gestational ages.
      There is a brief discussion on normal MRI anatomy of the fetal brain. There were
      45 studies that concerned central nervous system pathology, and the most frequent
      malformative and neoplastic disorders were revealed. A comparison between MRI and
      US is proposed for each. In conclusion, MRI can be regarded as a complementary
      method that can be helpful in the rare cases when the US diagnosis is doubtful.

PMID- 9660114
TI  - Extrapontine myelinolysis caused by electrolyte imbalance during the management
      of suprasellar germ cell tumors. Report of two cases.
AB  - Extrapontine myelinolysis (EPM) is caused by marked fluctuation of the serum
      electrolyte level. Patients with suprasellar germ cell tumors frequently present
      with diabetes insipidus, which is often aggravated by administration of steroid
      hormone. In addition, cisplatin-based chemotherapy is sometimes accompanied by
      marked serum electrolyte fluctuation because it needs massive hydration to
      prevent renal damage. Two children with suprasellar germ cell tumors in whom EPM
      developed secondary to profound hyponatremia and was rapidly corrected are
      described. The central pons was spared in both cases. Clinically the children
      showed transient neurological deficits including confusion, pseudobulbar palsy,
      and deterioration of consciousness. MRI demonstrated bilateral symmetrical, high
      signal-intensity (HSI) lesions on T2-weighted images (T2WI) at the basal ganglia
      and adjacent cerebral cortex. Follow-up T1WI a few months later revealed newly
      developed HSI lesions in the basal ganglia. The patients gradually improved, but
      the neurological deficits did not completely disappear. During the perioperative
      management of suprasellar germ cell tumors, EPM should be considered when a
      patient has a significant electrolyte imbalance and neurological deficits,
      especially confusion and pseudobulbar palsy.

PMID- 9660115
TI  - The multifarious use of stereotactic instrumentation.

PMID- 9660116
TI  - Transient "cerebellar" mutism.
AB  - The term "cerebellar mutism" refers to a specific disorder in which a complete
      but transient loss of speech, followed by dysarthria, occurs following resection
      of intrinsic posterior cranial fossa tumors or cerebellar hemorrhages, or upon
      trauma. Although it is well known that the lack of long-tract findings and
      cranial nerve (CN) involvement is the rule, the pathophysiology of cerebellar
      mutism has not been clearly elucidated. A review of the relevant literature
      disclosed 93 patients with this condition, the majority of these being in the
      pediatric age group. The neuropathological findings were as follows: 57 primitive
      neuroectodermal tumors (PNET), 19 astrocytomas, 10 ependymomas, 5 vascular
      malformations, 1 metastatic tumor, and 1 traumatic injury. The interval before
      the onset of mutism ranged from 0 to 168 h (mean 40.9 h). The mutism lasted from
      1 to 168 days (mean 37.6 days). Subsequent dysarthria was present in 75 (80%) of
      the 93 patients. In this article, some specific recent illustrative reports are
      presented, and the concept of the role of the cerebellum in language and
      cognition is discussed. With these data as our point of departure, various
      hypotheses that have been advanced to explain the pathogenesis of this transient
      speech disorder are analyzed. The findings of the study suggest that the cause of
      the cerebellar mutism is the ischemia caused by vasospasm, as it usually
      developed after a latent period.

PMID- 9660117
TI  - Pediatric brain stem gliomas: an update.
AB  - It has become evident that pediatric brain stem gliomas are a heterogeneous
      pathology and should be classified according to clinical and radiological
      criteria. This classification has contributed to better treatment and greatly
      improved prognosis. Based on a review of the literature, we describe the
      different types of brain stem astrocytomas reported, which are: cervicomedullary,
      exophytic, cystic, focal and diffuse. Particular attention is paid to therapeutic
      modalities. For the first three lesions named the treatment is surgical and
      oncological therapy should be evaluated only for regrowth of the mass. Focal
      tumors of the medulla and pons are still treated empirically (surgically and/or
      with radiotherapy), because a definitive therapeutic protocol has not yet been
      elaborated; on the other hand it is well established that if the focal mass is in
      the midbrain this should merely be monitored by means of serial MRI, while
      radiotherapy should be applied in the event of the tumor's growth. Diffuse
      gliomas are treated with oncological therapy, and surgery (for biopsy or tumor
      excision) is not indicated. Five illustrative cases from our department are
      presented.

PMID- 9660118
TI  - Pediatric pineal tumors: need for a direct surgical approach and complications of
      the occipital transtentorial approach.
AB  - In an investigation of the benefits and risks of direct surgical approaches to
      pediatric pineal tumors, the need for such approaches, the feasibility of
      surgical removal and operative complications were evaluated in 25 histologically
      proven cases. Five tumors were germinomas (GEs) or GE-predominant mixed germ cell
      tumors (GCTs), in which stereotactic biopsy can be adequate. Twenty of the 25
      pineal tumors (80%) were teratomas (TEs), TE-predominant mixed GCTs or other
      tumors that need direct surgical approaches. Among the 21 tumors resected by the
      occipital transtentorial (OTT) approach, 13 were removed radically (>95%) and 6
      others, subtotally (>75%). Complications of using the OTT approach included
      homonymous hemianopsia (7), Parinaud's syndrome (6), other eyeball movement
      limitation (7), seizure (5), and new hydrocephalus (3). The majority of these
      were transient, resolving within a few days or months, or easily controlled. The
      results showed that 80% of pediatric pineal tumors needed direct surgical
      approaches and that the majority were successfully removed by OTT surgery with an
      acceptable level of risk.

PMID- 9660119
TI  - Late neuropsychological and behavioural outcome of children surgically treated
      for craniopharyngioma.
AB  - Late outcome in 12 children treated by radical surgery for craniopharyngioma is
      presented. None of the patients presented underwent fractionated traditional or
      stereotactic radiotherapy. The results show no neurological (except visual
      dysfunction in 6 subjects), cognitive or short-term memory deficits. Three
      children were found to have a minor attention deficit. In 5 cases "frontal lobe"
      malfunctioning was disclosed, and in 5 there were bursts of unpredictable anger.
      Three children showed worsening of functioning at school: a combination of
      various causes is suggested to explain the worsening of academic performances.
      The size of the sample calls for a careful evaluation of results, with due
      consideration for the influence of various factors on outcome. Multicentre
      studies are required to increase the sample size and achieve more general
      conclusions.

PMID- 9660120
TI  - Intraoperative anaphylaxis during neurosurgery.
AB  - Intra-operative anaphylaxis is of particular concern in neurosurgery. Not only is
      there an increased risk of major anaphylaxis, but the frequent placement of
      patients in the prone or sitting position may make resuscitation difficult. We
      describe two cases of per-operative anaphylaxis during neurosurgery and the
      techniques used in the successful management and investigation of these patients.

PMID- 9660121
TI  - Continuous spikes and waves during sleep in children with shunted hydrocephalus.
AB  - Focal epileptiform abnormalities in awake children submitted to ventricular
      shunting are well described in the literature, but there are few reports about
      EEG patterns during sleep. We studied 20 children affected by hydrocephalus of
      various aetiology and submitted to shunting during the first year of life. We
      found focal abnormalities in all the children and in 95% of cases they were on
      the same side as the shunt; in 65% of cases they had an amplitude of 300 mV or
      more. During sleep there was activation of abnormalities in all subjects, and in
      33% we found continuous spikes and waves during slow sleep (CSWS). We discuss the
      aetiology of CSWS and its possible role in causing the neuropsychological
      disturbances of our patients.

PMID- 9660122
TI  - Severe head injury in children--analyzing the better outcome over a decade and
      the role of major improvements in intensive care.
AB  - We suggest a few possible explanations, including improvement of intensive care,
      as the main cause, for the improved outcome after severe head injury in children
      and present the predictors of outcome observed in a contemporary series. From
      January 1984 to June 1988 we saw 117 children (ages 0-14) with postresuscitation
      GCS (Glasgow Come Scale) scores of 3-8. The more recent cohort of children seen
      in 1994-1996 was made up of 152 patients. Apart from standard statistics we used
      a segmentation method called CHAID (SSPS software). Previously known predictors
      of outcome are found still to apply in our series. Although in the recent period
      there was a lower proportion of patients with GCS 3-4 (11% versus 32%), a higher
      percentage had suffered multiple trauma (56% versus 33%). The rates of craniotomy
      and of ICP monitoring were similar (66% and 61%). Comparison of the two cohorts
      for outcome at discharge and through 1 year shows that mortality fell from 33% to
      10% and the proportion achieving improvement of neurological status increased
      from 24% to 56%. CHAID analysis showed that the mortality rates of patients
      within specific groups declined significantly over the two periods: (1) a
      significant reduction in mortality was seen in patients with GCS 5-7, especially
      those with diffuse axonal injury (DAI) (17.3% to 0%); (2) no child admitted in
      shock survived in the earlier period, whereas 7 with GCS 4-6 survived during the
      recent period. The best model for mortality prediction includes GCS, and in the
      GCS 4-7 subgroup, the presence of subdural hematoma. It seems that the trend
      toward better immediate outcome is continuous, and this is the more striking when
      the severity of injury is taken into consideration. Our belief is that the modern
      medical and surgical techniques, although incurring higher costs and
      necessitating ongoing intensity, are well worth the effort.

PMID- 9660123
TI  - Prevention of intraventricular hemorrhage during CSF shunt revisions by means of
      a flexible coagulating electrode. A preliminary report.
AB  - We report the preliminary results of a prospective study in 19 patients (22
      procedures) undergoing ventricular catheter replacement at the time of CSF shunt
      revision to determine the value of intraluminal coagulation by means of a
      flexible monopolar coagulating electrode in preventing ventricular hemorrhage
      following catheter removal. These patients had their first shunt implanted during
      infancy, and underwent shunt revision during the 1-year period between October
      1996 and October 1997. Sixteen patients were found to have adherent ventricular
      catheters, that necessitated the use of diathermy for their removal. In 10
      procedures electrocoagulation was applied to the stylet of the ventricular
      catheter thus permitting tube extraction. In the remaining 8 shunt revisions
      catheter removal was readily accomplished by coagulation applied to a flexible
      monopolar endoscopic electrode introduced into the lumen of the tube. Two
      patients developed mild intraventricular hemorrhage following the use of each of
      the two methods described above. Both coagulation techniques used during the
      routine withdrawal of ventricular catheters seem to be equally effective. The
      flexible coagulating electrode has the additional advantage over the stylet of
      being moldable, allowing its use in cases in which the catheter does not follow a
      straight course within the ventricular cavity.

PMID- 9660124
TI  - An Odyssey of a pediatric neurosurgeon.

PMID- 9660125
TI  - Massive plexiform neurofibroma in the orbit in a child with von Recklinghausen's
      disease.
AB  - We report a case of orbital plexiform neurofibroma presenting in a 10-year-old
      boy with von Recklinghausen's neurofibromatosis. The patient had shown a slow
      enlargement of exophthalmos of the right eye present since birth, together with
      multiple cafe au lait spots on the skin of the trunk. Magnetic resonance (MR)
      images revealed diffuse and irregular nodular involvement of the retrobulbar
      nerves within the muscle cone, which was confirmed at the surgery. The tumour
      extended into the ipsilateral cavernous sinus. We discuss the MR findings as
      pathognomonic signs of this rare orbital tumour, including its multinodular
      nature among dispersed intraconal fat tissue, location around the optic nerve,
      extension through the superior orbital fissure into the cavernous sinus and
      association with von Recklinghausen disease.

PMID- 9660126
TI  - Temporal osteoclastoma: an exceptional lesion in infancy.
AB  - Osteoclastoma is a rare skeletal lesion, characterized by large multinucleated
      giant osteoclastic cells; this lesion usually affects young adults with a
      prevalence of 1 case/1 million population. We report the case of a 9-year-old
      girl with a right temporal tumescence: X-ray, CT and MRI revealed the presence of
      a right temporal hyperostotic ring-like area over the lambdoid suture, with
      irregular margins and calcareous deposits. The tumour was expanding mainly toward
      the endocranium involving both cranial tables and diploe, without infiltrating
      the brain parenchyma. The child underwent complete microsurgical removal of the
      lesion. Histopathological findings revealed the giant cell tumour osteoclastoma.
      Correct modern preoperative neuroimaging workup, coupled with microneurosurgical
      technique, allowed successful lesion removal with good outcome. A review of the
      more recent literature and of mechanisms of pathology together with
      neuroradiological protocol and results of treatment are discussed.

PMID- 9660128
TI  - Intraneural cyst of the peroneal nerve.
AB  - A 15-year-old girl was referred to us because of foot drop. The motor deficit was
      characterized by a peculiar fluctuating course related to sporting activity:
      improvement of symptoms during no-sport periods and worsening during sport
      training. Neurophysiological examination revealed marked global impairment of
      muscles innervated by the peroneal nerve. Ultrasound and MRI showed a mass in
      close proximity to the neck of the fibula extending in a tubular fashion. At
      operation an intraneural lesion was found and was totally removed. Histology
      revealed that it was an intraneural cyst. A hypothesis on the pathogenesis was
      drawn up. One year after the operation a clinical and neurophysiological follow
      up was performed.

PMID- 9660127
TI  - Leptomeningeal angiomatosis accompanied by hair follicle nevus.
AB  - A 5-day-old male infant with leptomeningeal angiomatosis accompanied by hair
      follicle nevus and congenital alopecia is reported. Admitted for frequent left
      hemiconvulsions, he had three small papular lesions around his right eye and
      ipsilateral alopecia from the frontal to parietal areas. Histopathological
      examination of the papular lesions revealed crowding of hair follicles. There
      were no other skin lesions and no ophthalmic abnormalities. Ictal EEG showed a
      theta burst in the right parietal area. Computed tomography of the brain revealed
      cerebral atrophy and a slightly high intensity lesion in the right parietal and
      occipital lobes with calcification. Gyriform enhancement was demonstrated by
      contrast MRI in these areas. The pathogenesis is discussed. This case may
      represent a previously unknown neurocutaneous syndrome.

PMID- 9660129
TI  - In memoriam Karl Enigk. German Society of Parasitologists.

PMID- 9660130
TI  - In memoriam Karl Enigk. 23 October 1906-29 December 1997.

PMID- 9660131
TI  - Biological effects of gamma-irradiation on laboratory and field isolates of
      Eimeria tenella (Protozoa; Coccidia).
AB  - Sporulated oocysts of a field strain (FS-111) and a laboratory strain (WIS) of
      Eimeria tenella were exposed to 0, 50, 100, 150, or 200 Gy of gamma-radiation
      from a 60Co source. Irradiated oocysts of WIS and FS-111 were not significantly
      more fragile after irradiation as shown by the release of sporocysts after 5-105
      s of vortex agitation with glass beads. Excystation was normal in both strains
      after treatment of the sporocysts with trypsin and sodium taurodeoxycholate, even
      in groups exposed to 200 Gy of radiation. Sporozoite release from irradiated
      sporocysts was more rapid than that from unirradiated sporocysts, primarily
      because of a shorter lag phase during the first 30 min. Irradiated sporozoites
      were slower to parasitize cultured chick kidney cells than were control
      sporozoites (4 h postinoculation), but after 24 h there was no significant
      difference (P < 0.05) between irradiated and control groups except for the WIS
      treated with 200 Gy. After 48 h, developing schizonts were reduced by 77-94% on
      exposure to 50-200 Gy. Strain FS-111 did not develop as well as WIS in vitro, but
      the effect of irradiation was similar. When irradiated oocysts of WIS or FS-111
      were inoculated into chickens the prepatent period was unaffected, but fewer
      oocysts were produced, lesion scores were lower, and the weight gain was less
      strongly affected in proportion to the doses of radiation. These results suggest
      that the effects of radiation damage were largely confined to the mechanism of
      nuclear and cellular reproduction rather than other physiological processes.

PMID- 9660132
TI  - Characterization of axenic isolates of Giardia intestinalis established from
      humans and animals in Germany.
AB  - A total of 15 isolates of Giardia intestinalis, the first axenic cultures of this
      organism to be described from Germany, were established in Bonn from faecal cysts
      obtained from human and animal stool specimens. Measurement of in vitro growth
      kinetics for 12 of the isolates revealed 3 phenotypes ('rapid', 'medium-rate' and
      'slow' growers) characterized by generation times of 9-11 h (5 isolates), 12-15 h
      (5 isolates) and > or = 18-20 h (2 isolates), respectively. Cloned sublines
      exhibited growth rates similar to those of the parent isolates. Genetic analyses
      involving use of the polymerase chain reaction to amplify segments of genes
      encoding variant-specific surface proteins or the enzyme glutamate dehydrogenase,
      coupled with the detection of restriction-fragment-length polymorphisms,
      identified genotypes belonging to three previously described genetic groups.
      Seven isolates (from humans, a calf and a chinchilla) were typed to genetic group
      I--a potentially zoonotic genotype belonging to assemblage A, one of two major
      genetic lineages defined by analysis of G. intestinalis from humans and animals.
      Six isolates (all from humans) showed identity with the group II genotype-
      recovered thus far only from humans and also belonging to assemblage A. Two
      isolates (one from a human, the other from a monkey housed at the Cologne zoo)
      were classified as assemblage B genotypes. The in vitro growth rates correlated
      strongly with genotype, group I or group II (assemblage A) genotypes accounting
      for all of the 'rapid' and 'medium-rate' cultures and both assemblage B isolates
      being 'slow growers'. The data indicate that genetically based metabolic
      differences may determine how rapidly G. intestinalis isolates can grow in axenic
      culture.

PMID- 9660133
TI  - Cytopathic effect of Blastocystis hominis after intramuscular inoculation into
      laboratory mice.
AB  - The present study investigated the pathogenesis of Blastocystis hominis by
      intramuscular injection of the organism into experimental mice. A total of 27
      naive BALB/c mice aged 6-8 weeks were injected in the leg muscle with axenic
      culture isolate B of B. hominis. Histological examination at different times
      revealed that B. hominis could produce a severe inflammatory reaction and
      myonecrosis. Most changes were observed at 6 h after injection and for up to 2-3
      days. By 2 weeks the muscle had regained normal histology. There was infiltration
      of polymorphonuclear leukocytes (PML) into the injection site, indicating that B.
      hominis had a strong chemoattractant activity for PML.

PMID- 9660134
TI  - Stimulation of human immunodeficiency virus expression in permanent monocytic
      cells by Sarcocystis gigantea extract.
AB  - As recently reported, a strong stimulation of noninfected CD4+ H9- cells by
      Sarcocystis gigantea (syn. S. ovifelis) extract (SGE) was observed using the
      lymphocyte proliferation assay. After SGE prestimulation, human immunodeficiency
      virus (HIV)-infected H9+ cells showed an exacerbation of viral replication. In
      the present study we investigated the reactivity of HIV-infected human monocytes
      using SGE. The highly sensitive p24 core-profile enzyme-linked immunosorbent
      assay (ELISA) was used to examine directly the amount of HIV produced.
      Experiments were performed using U937 permanent monocytic cells. Permanent
      incubation as well as preincubation with SGE before virus infection stimulated
      HIV expression in all the cells. In U937 cells the viral release per cell was 64
      times higher on permanent stimulation with 320 microg SGE relative to controls
      and 9 times higher following prestimulation.

PMID- 9660135
TI  - Colonization and seasonality of goby (Gobiidae, Teleostei) parasites from the
      southwestern Baltic Sea.
AB  - A comparative parasitology study of gobiid fishes from two sites on the western
      Baltic Sea was done to get information on the quality of the respective
      environments. The parameters used were the infracommunity, the species numbers
      and abundance with respect to the size classes of the hosts, and the abundance
      with respect to the seasons. The hosts, Gobius niger, Gobiusculus flavescens,
      Pomatoschistus minutus, and P. pictus, were caught at Blank Eck (Kiel Bight) and
      Dahmeshoved (Lubeck Bight) during 1992 and 1993. The infracommunities of
      Dahmeshoved attained higher rates of prevalence of helminth parasites than did
      those of Blank Eck, as was valid in all host specimens harboring one or two
      parasite species. The group bearing three parasite species was present in
      Dahmeshoved but absent in Blank Eck. Parasite species numbers, which were similar
      in the two sites, increased from the smallest to the largest hosts but changed
      with growth. With one exception, this result is also valid for the abundance,
      which clearly differed between the hosts and between the sites. Whereas species
      numbers as well as abundance rates were low in spring, they increased in summer.
      The results reveal that the composition of infracommunities depends on the local
      parasite fauna and on the strength of general host defense mechanisms, whereas
      that of the component community is dependent on the susceptibility of hosts to
      single parasite species and on the density of intermediate parasite stages. This
      is also the reason for the stronger infestation of hosts from Dahmeshoved as
      opposed to those from Blank Eck, where the degree of eutrophication is lower and,
      therefore, fewer herbivorous intermediate hosts can exist.

PMID- 9660136
TI  - Redescription of Babesia equi Laveran, 1901 as Theileria equi Mehlhorn, Schein
      1998.
AB  - The horse-parasitizing species Babesia equi Laveran, 1901 was redescribed as
      Theileria equi Mehlhorn, Schein 1998 and, thus, transferred from one valid genus
      to another. This transfer was needed since it turned out that this horse parasite
      showed the relevant characteristics of theilerians with regard to biological
      data, morphological features, biochemical properties, and molecular biological
      relationships.

PMID- 9660137
TI  - Scanning electron microscopy of Blastocystis hominis cysts.
AB  - Scanning electron microscopy of Blastocystis hominis cysts reveals that some
      cysts have an outer coat, whereas others are naked. If intact, the outer coat
      forms a fan-like structure around the cyst and its surface is granular. The
      fragmented outer coat adheres to other cysts and bacteria, forming irregular
      clumps.

PMID- 9660138
TI  - Mitochondrial 16S rDNA sequences and phylogenetic relationships of species of
      Rhipicephalus and other tick genera among Metastriata (Acari: Ixodidae).
AB  - The mitochondrial 16S rRNA gene sequences of the following eight European
      Metastriata tick species were obtained by direct polymerase-chain-reaction cycle
      sequencing and silver-staining methods: Rhipicephalus bursa, R. pusillus, R.
      sanguineus, R. turanicus, Boophilus annulatus, Dermacentor marginatus,
      Haemaphysalis punctata, and Hyalomma lusitanicum. This mitochondrial gene seems
      to be a good marker for the establishment of genetic relationships among closely
      related tick species, but it does not seem to be useful for comparisons of
      distantly related taxa. The molecular data provide very strong support for the
      monophyly of the Rhipicephalinae, including Hyalomma spp. However, the genus
      Rhipicephalus may not be considered a monophyletic group; in all analyses carried
      out in this study, R. bursa clustered with Boophilus spp. The high percentage of
      similarity (98.7%) observed between R. sanguineus and R. turanicus sequences
      would suggest that these species recently diverged within the Rhipicephalus
      genus. Phylogenetic analyses showed a monophyletic relationship among
      Amblyomminae taxa. The relationships between Haemaphysalis species and the true
      placement of this genus within Metastriata could not be resolved.

PMID- 9660139
TI  - Antibodies to nonrepeat sequences of antigen Pf155/RESA of Plasmodium falciparum
      inhibit parasite growth in vitro.
AB  - Immune responses to the repeat regions of the Plasmodium falciparum antigen
      Pf155/RESA have been extensively studied, and antibodies to the repeats are known
      to interfere with parasite growth both in vitro and in vivo. Less is known with
      regard to the effect on parasites of antibodies to the nonrepeat regions of the
      antigen. In the present study, rabbits were immunized with synthetic peptides
      corresponding to three different nonrepeated sequences of antigen Pf155/RESA. The
      reactivity of the antibodies with the particular peptides was analyzed by enzyme
      linked immunosorbent assay (ELISA) and that with the parasite antigen, by
      immunoblotting and immunofluorescence. Although all antisera reacted strongly
      with the corresponding synthetic peptides, they reacted only weakly with full
      length Pf155/RESA in either of the methods used. The specificity of the
      antibodies for Pf155/RESA was confirmed by their failure to stain Pf155/RESA
      deficient parasites in erythrocyte membrane immunofluorescence, a method mainly
      detecting this antigen. Antibodies to the nonrepeat sequences also efficiently
      inhibited the merozoite invasion in vitro of Pf155/RESA+ parasites. However,
      these antibodies also inhibited Pf155/RESA-deficient parasites, indicating the
      presence of an antigen exhibiting a high degree of homology with Pf155/RESA. The
      results indicate that nonrepeat sequences of Pf155/RESA are immunogenic and may
      serve as targets for parasite-neutralizing antibodies, and, thus, the potential
      of the antigen as a vaccine candidate is emphasized.

PMID- 9660140
TI  - Characterization of purified metallo- and cysteine proteases from the pathogenic
      haemoflagellate Cryptobia salmositica Katz 1951.
AB  - The purified metalloprotease and the partially purified cysteine protease from
      pathogenic Cryptobia salmositica were characterized. Using haemoglobin gel
      electrophoresis, we detected five enzymatic bands in crude parasite lysate; one
      protease (200 kDa) yielded a metalloprotease band and other four, cysteine
      protease bands (97, 70, 66 and 49 kDa). Both the metalloprotease and the cysteine
      protease had high levels of proteolytic activity against azocasein, haemoglobin
      and fibrinogen. The metalloprotease had high levels of activity against azocoll
      and gelatin but a low degree of activity against albumin. In contrast, the
      cysteine protease had extensive activity against albumin but low levels of
      activity against azocoll and gelatin. The metallo- and cysteine proteases had no
      activity against Pz-peptide, a specific substrate for bacterial collagenase. The
      optimal pH for the metalloprotease and the cysteine protease was 7.0 and 5.0,
      respectively. The metalloprotease was inhibited by metal-chelating agents and
      excess of zinc ions but was activated by calcium ions. The cysteine protease was
      inhibited by thiol-blocking agents. The natural antiprotease alpha2
      macroglobulin, but not alpha1-protease inhibitor, inhibited the activity of both
      proteases from C. salmositica. The optimal in vitro temperature for the purified
      metalloprotease was 30 degrees C.

PMID- 9660141
TI  - First description of the male and redescription of the female of Paratrichosoma
      recurvum (Nematoda: Capillariidae), a skin-invading parasite of crocodiles in
      Mexico.
AB  - The first description of the male and a redescription of the female of the
      nematode Paratrichosoma recurvum (Solger, 1877), a parasite of the abdominal skin
      of crocodiles, are presented on the basis of specimens collected from Crocodilus
      moreletii Dumeril et Bibron from the Lagoon of Celestun, Yucatan, Mexico. The
      morphology of P. recurvum proved to be very similar to that of the only other
      congeneric species, P. crocodylus Ashford et Muller, 1978, but the former
      differed from the latter in having distinctly protruding polar plugs on eggs,
      reduced mesenchymal cells at the esophagointestinal junction, and a smooth
      spicular surface as well as in geographic distribution. The finding of P.
      recurvum in C. moreletii represents a new host record. Paratrichosoma spp. appear
      to be widely distributed in tropical countries of different continents and may be
      of economic importance for crocodile farms.

PMID- 9660142
TI  - A DNA probe for the detection of Dicrocoelium dendriticum in ants of Formica spp.
      and Lasius spp.
AB  - Repetitive DNA sequences present in the genome of Dicrocoelium dendriticum were
      identified by hybridization of genomic DNA that had been digested with different
      restriction enzymes with 32P-labeled genomic D. dendriticum DNA. DNA fragments
      containing repetitive sequences were isolated from PstI-digested D. dendriticum
      DNA and were subcloned into a plasmid vector. Plasmids containing repetitive
      sequences were identified by colony hybridization. One of these plasmids,
      designated Ddr-IV, was isolated and used as a probe in further studies. Ddr-IV is
      specific for D. dendriticum since it does not hybridize to DNA isolated from
      other trematodes. In addition, Ddr-IV was capable of detecting D. dendriticum
      metacercariae in ants (Formica cunicularia, F. rufibarbis, and Lasius sp.), which
      act as second intermediate hosts in the parasite's life cycle. Since
      metacercariae constitute the infectious stage of the parasite for grazing
      animals, Ddr-IV will provide a useful tool for epidemiology studies of
      dicrocoeliosis.

PMID- 9660143
TI  - Synergy between Entamoeba histolytica and Escherichia coli in the induction of
      cytokine gene expression in human colon epithelial cells.
AB  - Entamoeba histolytica induces the expression and secretion of interleukin 8 (IL
      8) by cultured colon epithelial cells. We assessed the array of cytokine genes
      expressed by human colon epithelial cells in response to co-culture with E.
      histolytica trophozoites and tested the hypothesis that enteric bacteria may
      alter the E. histolytica-induced expression of such genes. HT-29 colon epithelial
      cells were co-cultured with E. histolytica trophozoites in the presence or
      absence of Escherichia coli. Cytokine gene expression was assessed by
      quantitative reverse-transcription polymerase chain reaction (RT-PCR). IL-8 mRNA
      in colon epithelial cells was up-regulated following exposure to E. histolytica
      and this was paralleled by increased IL-8 secretion. Granulocyte-macrophage
      colony-stimulating factor (GM-CSF) and IL-1alpha/beta mRNAs were also up
      regulated in these cells. When HT-29 cells were co-cultured with E. coli DH5alpha
      and E. histolytica there was a synergistic increase in the expression of IL-8, IL
      1alpha, and GM-CSF. These results suggest that enteric bacteria may significantly
      affect early proinflammatory signals produced in host tissues in response to E.
      histolytica infection.

PMID- 9660144
TI  - Morphologic, biometric, and isoenzyme characterization of Trichuris suis.
AB  - Trichuris suis isolates were collected from the cecum of Sus scrofa domestica
      (pig) and S. s. scrofa (wild boar). Morphology and biometry studies were carried
      out. Morphology studies showed the existence of typical caudal papillae in males
      of T. suis from wild boars, but no other difference was observed in the biometric
      parameters (total length, esophageal length, posterior-portion body length, and
      spicular length) of T. suis isolated from either host. Individual extracts were
      subjected to malate dehydrogenase (MDH), malic enzyme (ME), glucose 6-phosphate
      dehydrogenase (G6PD), lactate dehydrogenase (LDH), and superoxide dismutase (SOD)
      isoenzyme analysis following starch-gel electrophoresis, and the isoenzyme
      patterns were compared with those obtained from other species of trichurids. MDH,
      ME, G6PD, LDH, and SOD isoenzyme patterns were identical for T. suis from both
      hosts. MDH isoenzyme patterns were characterized by the presence of one cathodic
      isoenzyme. ME, G6PD, and LDH isoenzyme patterns indicated the presence of three
      phenotypes, whereas the SOD isoenzyme pattern showed only one phenotype
      characterized by the existence of two (anodic and cathodic) bands. Different LDH
      and SOD isoenzyme patterns observed for T. suis, T. ovis, and T. skrjabini
      confirm once more that isoenzyme patterns have potential as a diagnostic tool for
      differentiation of different species of Trichuris.

PMID- 9660145
TI  - Metabolism of [3-(13)C]-pyruvate by cysticerci of Taenia crassiceps.
AB  - Carbon-13 decoupled 1H spin-echo nuclear magnetic resonance (NMR) spectra, with
      and without 13C population inversion, of extracts of Taenia crassiceps cysticerci
      incubated in media containing [3-(13C)]-pyruvate showed 13C enrichment in
      alanine, lactate, acetate, succinate, and citrate. Labeling in the latter three
      metabolites provides substantial evidence that the malic enzyme reaction in this
      cestode also functions in the direction opposite to that in which it is normally
      portrayed. The direct passage of pyruvate from the cytosol to the mitochondrion
      is suggested by the greater percentage of 13C detected in acetate relative to
      succinate.

PMID- 9660147
TI  - The human monocyte locomotion-inhibitory factor produced by Entamoeba histolytica
      does not inhibit the locomotion of human eosinophils.

PMID- 9660146
TI  - The immunosuppressive compound FK506 does not affect expulsion of Echinostoma
      trivolvis in C3H mice.
AB  - C3H/HeN mice were infected with Echinostoma trivolvis metacercariae on day 0,
      given intramuscular injections of the immunosuppressive agent FK506 daily for 5
      or 7 days, and necropsied on days 5, 8, 12, 15, 20, and 30 postinfection (p.i.).
      Control mice were infected with the echinostomes but were not treated with FK506.
      A significant reduction in mastocytosis was seen from day 12 to day 15 p.i. in
      the treated group. No reduction was observed in numbers of goblet cells and
      eosinophils in the treated group. The number of white blood cells was lower in
      the treated mice than in the controls. No significant difference in the optical
      density values of immunoglobulins appeared in control versus treated mice.
      Treatment with FK506 did not delay worm expulsion markedly, probably because the
      drug did not suppress goblet-cell hyperplasia. Increased mucus production
      associated with goblet-cell hyperplasia is primarily involved in the expulsion of
      E. trivolvis in murine hosts.

PMID- 9660148
TI  - An improved method for the purification of Trypanosoma brucei variant surface
      glycoprotein.

PMID- 9660149
TI  - Exercise training in female patients with a family history of hypertension.
AB  - The purpose of this study was to determine whether there are differences in the
      effects of exercise training between those with a parental history of
      hypertension and those without such a history. A group of 39 middle-aged
      hypertensive women were submitted to a 4-month exercise training programme. On
      the basis of their family histories, 18 individuals were classified as those
      having a positive parental history of hypertension (group P) and 21 individuals
      as those without such a history (group N). Both groups participated in a
      supervised training programme with the intensity set at the level producing the
      threshold lactate concentration for 90-120 min twice a week, together with self
      determined aerobic exercise three times a week. Vital age was estimated to
      determine the health-fitness status. At the end of the training, group N
      exhibited reductions in the systolic and diastolic blood pressures at rest (12.6/
      8.0 mmHg) and increases in the peak oxygen uptake [VO2peak 21.1 (SD 5.2) vs 25.2
      (SD 5.7) ml x kg(-1) x min(-1)] and oxygen uptake corresponding to lactate
      threshold [13.7 (SD 2.4) vs 17.0 (SD 2.0) ml x kg(-1) min(-1); P < 0.05]. Group P
      also showed reductions in the resting blood pressures (8.9/2.9 mmHg; P < 0.05),
      with no change in VO2peak (P > 0.05). There were no changes in the blood lipid
      and haematocrit variables in either group. The vital age decreased by
      approximately 4 and 7 years (P < 0.05) for groups P and N, respectively. These
      results would indicate that exercise training is a useful, nonpharmacological
      tool for the treatment of essential hypertension, especially in patients with no
      family history of arterial hypertension.

PMID- 9660150
TI  - Influence of climate on heart rate in children: comparison between intermittent
      and continuous exercise.
AB  - Heart rate (HR) monitoring is commonly used to assess 24-h energy expenditure
      (EE) in children but it has been found to overestimate the true values. One
      reason for this may be the effect of climatic heat stress on HR. An equation has
      been previously developed to adjust HR measured during continuous exercise for
      the influence of climate. Since play in children is rarely of a continuous
      pattern, one objective of this study was to compare the effects of climatic heat
      stress on the HR response to intermittent and to continuous exercise. A second
      objective was to determine whether the previously developed equation is suitable
      for intermittent exercise. A group of 12 boys and 8 girls (aged 8-11 years)
      cycled in a climatic chamber. The exercise consisted of continuous cycling for 5
      min at 35%, 55%, and 75% of peak oxygen up take (random order) followed by
      alternating cycling at the same resistance and cadence (30 s) and rest (30 s) for
      3 additional min. The oxygen uptake (VO2) and HR were determined for 2 min at the
      end of continuous cycling and for 2 min during intermittent cycling. Climatic
      conditions (randomly assigned) were dry bulb temperature T(db) 22 degrees C, 50%
      relative humidity (rh); T(db) 28 degrees C, 55% rh; T(db) 32 degrees C, 52% rh;
      or T(db) 35 degrees C, 58% rh. The difference between HR measured at a given
      T(db) (HR(meas)) and HR at 22 degrees C and at the same VO2 was then calculated
      (deltaHR). The deltaHR increased linearly with increasing temperature but was not
      related to VO2 or to exercise type. However, a small but significant difference
      was found if the published equation was used with data from intermittent
      exercise. The accuracy of the existing equation adjusting HR(meas) for the
      influence of T(db) (HR(corr)) could be improved to HR(corr) = HR(meas) x (1.18308
      (0.0083218 x T(db))). In conclusion, the effects of climatic heat stress on HR
      were similar in continuous and intermittent exercise, and HR can be adjusted for
      the influence of climate in groups of pre- and early pubertal children during
      rest, intermittent and continuous exercise at ambient temperatures between 22
      degrees C and 35 degrees C, thereby reducing the error in predicting EE from HR.

PMID- 9660151
TI  - Intramuscular pressure, force and blood flow in rabbit tibialis anterior muscles
      during single and repetitive contractions.
AB  - The elevated intramuscular pressure (IMP) associated with sustained muscle
      contraction can affect blood flow, and could influence the long-term viability of
      functional skeletal muscle grafts. We therefore examined the relationship between
      force, peak IMP and blood flow in the tibialis anterior muscle of the
      anaesthetized rabbit. During isometric contractions. IMP was related linearly to
      force, and only the slope of the relationship varied between animals. During
      isotonic contractions, however, the highest values of IMP were found at the
      lowest force levels, and IMP appeared to be related to the amount and speed of
      shortening. During repeated isometric contractions, the ratio of IMP to force
      varied with time, stimulation pattern and subject. Mean blood flow did not differ
      appreciably between repetitive isometric contractions at duty cycles of 10-40%,
      and was unrelated to integrated pressure, integrated force, or depth from the
      surface. We conclude: (1) that IMP is unlikely to affect mean blood flow during
      cyclic activity that has a duty cycle less than 40%; and (2) that the clinical
      use of IMP as a predictor of muscle force appears to be justified only for single
      isometric contractions, and needs to be interpreted cautiously when contractions
      involve shortening or fatigue.

PMID- 9660152
TI  - Noninvasive skeletal muscle lactate detection between periods of intense exercise
      in humans.
AB  - We investigated whether localized 1H nuclear magnetic resonance spectroscopy
      (NMRS) using stimulated echoes (STEAM) with a long mixing time (t(m)) allowed the
      suppression of the fat signal and detection of lactate in skeletal muscle. The 1H
      NMRS sequence was first validated in three isolated and perfused rabbit biceps
      brachii muscles. Spectra were obtained on a wide-bore spectrometer using a dual
      tuned probe (1H and 31P). Death was simulated by ceasing the muscle perfusion,
      which allowed post-mortem changes to be followed. During and after the simulated
      death, changes in levels of pH and in content of energy-rich compounds were
      observed with 31P NMRS. Our results showed an inverse linear relationship between
      pH and lactate in each of the three rabbits (r = 0.93, P < 0.001; r = 0.92, P <
      0.01; r = 0.89, P < 0.01) and a decrease in phosphocreatine and concomitant
      increase in lactate. We then investigated whether this sequence allowed repeated
      detection of lactate in human soleus muscle during the recovery between periods
      of intense exercise (force-velocity test, F-v test). Seven subjects mean age 25.1
      (SEM 0.8) years participated in this study. Soleus muscle lactate was detected at
      rest and for 3 min 30 s of the 5-min recovery between periods using a 2.35-T 40
      cm bore magnet spectrometer. Arm venous plasma lactate concentration was measured
      at rest, during the F-v test when the subject stopped pedalling (S1), and at the
      end of each 5-min recovery between periods (S2). Results showed that the venous
      plasma lactate concentration at S1 and S2 increased significantly from the
      beginning of the F-v test to peak anaerobic power (W(an,peak)) (P < 0.001). The
      spectra showed that muscle lactate resonance intensity rose markedly when
      W(an,peak) was achieved. The muscle lactate resonance intensity plotted as a
      percentage of the resting value increased significantly at W(an,peak) compared
      with submaximal braking forces (P < 0.05). We concluded from these results that
      localized 1H NMRS using STEAM with a long t(m) allows suppression of the fat
      signal and repeated detection of lactate on isolated perfused skeletal muscle in
      animals and between periods of intense exercise in humans.

PMID- 9660153
TI  - Sex-related differences in thermoregulatory responses while wearing protective
      clothing.
AB  - This study examined the thermoregulatory responses of men (group M) and women
      (group F) to uncompensable heat stress. In total, 13 M [mean (SD) age 31.8 (4.7)
      years, mass 82.7 (12.5) kg, height 1.79 (0.06) m, surface area to mass ratio 2.46
      (0.18) m2 x kg(-1) x 10(-2), Dubois surface area 2.01 (0.16) m2, %body fatness
      14.6 (3.9)%, VO2peak 49.0 (4.8) ml x kg(-1) x min(-1)] and 17 F [23.2 (4.2)
      years, 62.4 (7.7) kg, 1.65 (0.07) m, 2.71 (0.14) m2 x kg(-1) x 10(-2), 1.68
      (0.13) m2, 20.2 (4.8)%, 43.2 (6.6) ml x kg(-1) x min(-1), respectively] performed
      light intermittent exercise (repeated intervals of 15 min of walking at 4.0 km x
      h(-1) followed by 15 min of seated rest) in the heat (40 degrees C, 30% relative
      humidity) while wearing nuclear, biological, and chemical protective clothing
      (0.29 m2 x degrees C x W(-1) or 1.88 clo, Woodcock vapour permeability
      coefficient 0.33 i(m)). Group F consisted of eight non-users and nine users of
      oral contraceptives tested during the early follicular phase of their menstrual
      cycle. Heart rates were higher for F throughout the session reaching 166.7 (15.9)
      beats x min(-1) at 105 min (n = 13) compared with 145.1 (14.4) beats x min(-1)
      for M. Sweat rates and evaporation rates from the clothing were lower and average
      skin temperature (T(sk)) was higher for F. The increase in rectal temperature
      (T(re)) was significantly faster for the F, increasing 1.52 (0.29) degrees C
      after 105 min compared with an increase of 1.37 (0.29) degrees C for M. Tolerance
      times were significantly longer for M [142.9 (24.5) min] than for F [119.3 (17.3)
      min]. Partitional calorimetric estimates of heat storage (S) revealed that
      although the rate of S was similar between genders [42.1 (6.6) and 46.1 (9.7) W x
      m(-2) for F and M, respectively], S expressed per unit of total mass was
      significantly lower for F [7.76 (1.44) kJ x kg(-1)] compared with M [9.45 (1.26)
      kJ x kg(-1)]. When subjects were matched for body fatness (n = 8 F and 8 M),
      tolerance times [124.5 (14.7) and 140.3 (27.4) min for F and M, respectively] and
      S [8.67 (1.44) and 9.39 (1.05) kJ x kg(-1) for F and M, respectively] were not
      different between the genders. It was concluded that females are at a
      thermoregulatory disadvantage compared with males when wearing protective
      clothing and exercising in a hot environment. This disadvantage can be attributed
      to the lower specific heat of adipose versus non-adipose tissue and a higher
      percentage body fatness.

PMID- 9660154
TI  - Rectal and esophageal temperatures during upper- and lower-body exercise.
AB  - This study investigated the question: is core temperature measurement influenced
      by whether exercise involves predominantly upper- or lower-body musculature?
      Healthy men were allocated to three groups: treadmill ergometry (T) n = 4, cycle
      ergometry (C) n = 6 and arm crank ergometry (AC) n = 5. Subjects underwent an
      incremental exercise test to exhaustion on an exercise-specific ergometer to
      determine maximum/peak oxygen consumption (VO2max). One week later subjects
      exercised for 36 min on the same ergometer at approximately 65% VO2max while
      temperatures at the rectum (T(re)) and esophagus (T(es)) were simultaneously
      measured. The VO2max (1 x min(-1)) for groups T [4.76 (0.50)] and C [4.35 (0.30)]
      was significantly higher than that for the AC group [2.61 (0.24)]. At rest, T(re)
      was significantly higher than T(es) in all groups (P < 0.05). At the end of
      submaximal exercise in the C group, T(re) [38.32 (0.11) degrees C] was
      significantly higher than T(es) [38.02 (0.12) degrees C, P < 0.05]. No
      significant differences between T(re) and T(es) at the end of exercise were noted
      for AC and T groups. The temperature difference (T(diff)) between T(re) and T(es)
      was dissimilar at rest in the three groups; however, by the end of exercise
      T(diff) was approximately 0.2 degrees C for each of the groups, suggesting that
      at the end of steady-state exercise T(re) can validly be used to estimate core
      temperature.

PMID- 9660155
TI  - Substrate use during and following moderate- and low-intensity exercise:
      implications for weight control.
AB  - Substrate utilization during and after low- and moderate-intensity exercise of
      similar caloric expenditure was compared. Ten active males [age: 26.9 (4.8)
      years; height: 181.1 (4.8) cm; Mass: 75.7 (8.8) kg; maximum O2 consumption
      (VO2max): 51.2 (4.8) ml x kg(-1) x min(-1)] cycled at 33% and 66% VO2max on
      separate days for 90 and 45 min, respectively. After exercise, subjects rested in
      a recumbent position for 6 h. Two h post-exercise, subjects ate a standard meal
      of 66% carbohydrate (CHO), 11% protein, and 23% fat. Near-continuous indirect
      calorimetry and measurement of urinary nitrogen excretion were used to determine
      substrate utilization. Total caloric expenditure was similar for the two trials;
      however, significantly (P < 0.05) more fat [42.4 (3.6) g versus 24.0 (12.2) g]
      and less CHO [142.5 (28.5) g versus 188.8 (45.2) g] was utilized as a substrate
      during the low-intensity compared to the moderate-intensity trial. Protein
      utilization was similar for the two trials. The difference in substrate use can
      be attributed to the exercise period because over twice as much fat was utilized
      during low-intensity [30.0 (11.0) g] compared to moderate-intensity exercise
      [13.6 (6.6) g]. Significantly more (P < 0.05) CHO was utilized during the
      moderate-intensity [106.0 (27.8) g] compared to the low-intensity exercise [68.7
      (20.0) g]. Substrate use during the recovery period was not significantly
      different. We conclude that low-intensity, long-duration exercise results in a
      greater total fat oxidation than does moderate intensity exercise of similar
      caloric expenditure. Dietary-induced thermogenesis was not different for the two
      trials.

PMID- 9660156
TI  - Influence of short-term aerobic training and hydration status on tolerance during
      uncompensable heat stress.
AB  - The purpose of the present study was to determine the separate and combined
      effects of a short-term aerobic training program and hypohydration on tolerance
      during light exercise while wearing nuclear, biological, and chemical protective
      clothing in the heat (40 degrees C, 30% relative humidity). Males of moderate
      fitness [< 50 ml x kg(-1) x min(-1) maximal O2 consumption (VO2max)] were tested
      while euhydrated or hypohydrated by approximately 2% of body weight through
      exercise and fluid restriction the day preceding the trials. Tests were conducted
      before and after either a 2-week program of daily aerobic training (1 h treadmill
      exercise at 65% VO2max for 12 days; n = 8) or a control period (n = 7), which had
      no effect on any measured variable. The training increased VO2max by 6.5%, while
      heart rate (f(c)) and the rectal temperature (T(re)) rise decreased during
      exercise in a thermoneutral environment. In the heat, training resulted in a
      decreased skin temperature and increased sweat rate, but did not affect f(c),
      T(re) or tolerance time (TT). In both training and control groups, hypohydration
      significantly increased T(re) and f(c) and decreased the TT. It was concluded
      that the short-term aerobic training program had no benefit on exercise-heat
      tolerance in this uncompensable heat stress environment.

PMID- 9660157
TI  - Determinants of maximal instantaneous muscle power in women aged 50-75 years.
AB  - The present study aimed at analysing the age-related decline in maximal muscle
      power (W) in 52 sedentary healthy women aged between 50 and 75 years to determine
      whether force or velocity is the major determinant. Maximal muscle power was
      estimated from two types of vertical jumps, squatting (SJ) and countermovement
      (CmJ), performed on a force platform. It was obtained by measuring the vertical
      force (F(opt)) applied to the body centre of gravity and calculating the
      corresponding vertical velocity (v(opt)). An age-related decline in absolute W
      was statistically significant in all the conditions examined and in both peak W
      and average power (W) values. The decrease in v(opt) was also statistically
      significant. Also F(opt) declined but this reduction was not statistically
      significant with the exception of the average value in CmJ. Not surprisingly the
      highest W were obtained in CmJ, and the difference in power production between
      the two types of jump showed an age-related decrement only in W. The main finding
      of the study was the demonstration that v(opt) was the critical determinant of
      the age-related decline in W in healthy elderly women.

PMID- 9660158
TI  - Lower leg fluid displacement during a simulated space shuttle launch.
AB  - Reductions in leg fluid volume of about 1/per leg or 10% of total leg volume have
      been reported during space flight. We wanted to test the hypothesis that a
      significant portion of these changes occur during the prelaunch and launch
      periods. Fluid volume changes in the lower leg were estimated in six men during a
      simulated Space Shuttle launch. After 2 h in the launch position, i.e. supine
      with elevated legs, the subjects were exposed to 500 s of two to three times
      increased g force in the anterio-posterior direction in a human centrifuge.
      During the prelaunch period one lower leg lost a mean of (113 SD 53) ml of fluid
      and there was little or no additional fluid reduction during the period of
      increased g force. This compares with the 178-ml reduction of lower leg volume
      that has been reported during the 1st day of Shuttle missions. We concluded that
      a significant portion of the fluid reduction observed in the lower leg during the
      early stages of space flight had already occurred before the launch.

PMID- 9660159
TI  - The effects of short-term resistance training on endocrine function in men and
      women.
AB  - This investigation examined hormonal adaptations to acute resistance exercise and
      determined whether training adaptations are observed within an 8-week period in
      untrained men and women. The protocol consisted of a 1-week pre-conditioning
      orientation phase followed by 8 weeks of heavy resistance training. Three lower
      limb exercises for the quadriceps femoris muscle group (squat, leg press, knee
      extension) were performed twice a week (Monday and Friday) with every other
      Wednesday used for maximal dynamic 1 RM strength testing. Blood samples were
      obtained pre-exercise (Pre-Ex), immediately post-exercise (IP), and 5 min post
      exercise (5-P) during the first week of training (T-1), after 6 weeks (T-2) and 8
      weeks (T-3) of training to determine blood concentrations of whole-blood lactate
      (LAC), serum total testosterone (TT), sex-hormone binding globulin (SHBG),
      cortisol (CORT) and growth hormone (GH). Serum TT concentrations were
      significantly (P < or = 0.05) higher for men at all time points measured. Men did
      not demonstrate an increase due to exercise until T-2. An increase in pre
      exercise concentrations of TT were observed both for men and women at T-2 and T
      3. No differences were observed for CORT between men and women; increases in CORT
      above pre-exercise values were observed for men at all training phases and at T-2
      and T-3 for women. A reduction in CORT concentrations at rest was observed both
      in men and women at T-3. Women demonstrated higher pre-exercise GH values than
      men at all training phases; no changes with training were observed for GH
      concentrations. Exercise-induced increases in GH above pre-exercise values were
      observed at all phases of training. Women demonstrated higher serum
      concentrations of SHBG at all time points. No exercise-induced increases were
      observed in men over the training period but women increased SHBG with exercise
      at T-3. SHBG concentrations in women were also significantly higher at T-2 and T
      3 when compared to T-1 values. Increases in LAC concentrations due to exercise
      were observed both for men and women for all training phases but no significant
      differences were observed with training. These data illustrate that untrained
      individuals may exhibit early-phase endocrine adaptations during a resistance
      training program. These hormonal adaptations may influence and help to mediate
      other adaptations in the nervous system and muscle fibers, which have been shown
      to be very responsive in the early phase of strength adaptations with resistance
      training.

PMID- 9660160
TI  - Normative data for strength and flexibility of women throughout life.
AB  - Previously established normative data for muscular strength, endurance and the
      flexibility of women have recently been criticized as being unreliable.
      Furthermore, no normative data for the muscular fitness of women over 70 years of
      age are established. The purpose of this study was to derive normative data for
      muscular fitness in women 20-70+ years old, and to compare these data to the most
      recently published norms of the American College of Sports Medicine (ACSM). A
      total of 304 independent-living women were evaluated for maximal performance of
      bench press, leg press, modified push-ups, grip strength, and sit-and-reach.
      Tables of normative values for each measurement were generated along with
      percentile rankings. Large discrepancies were found between these new data and
      those of the ACSM norms. Bench press norms from ACSM are comparatively high so
      that the average woman in this current sample scored below the 10th percentile of
      the ACSM rankings. Similarly, the average woman in our sample ranked in either
      the poor or fair category of the ACSM norms for modified push-ups, and in the
      poor ACSM category for sit-and-reach. In contrast, leg press scores for the
      average woman in this study fell within the good or excellent category of the
      ACSM norms, suggesting that the ACSM norms are too low. Grip strength for the
      middle-aged women in this study was higher than that in previous norms. These
      newly established norms are better suited for interpreting women's fitness test
      results than previously published norms.

PMID- 9660161
TI  - Effect of creatine supplementation during rapid body mass reduction on metabolism
      and isokinetic muscle performance capacity.
AB  - Well-trained subjects (n = 6) were studied before and after losing a mean 3.0%
      4.3% of body mass to determine whether muscle performance could be maintained or
      even enhanced by dietary creatine supplementation. During a 5-day period of loss
      of mass the subjects were randomly assigned to a creatine or placebo supplemented
      diet. All the subjects were measured before and after loss of mass on both
      supplements for isokinetic peak torque (PT) and work at peak torque (W(PT)) of
      knee extensors, also for intermittent high intensity working capacity of the same
      muscle group. The latter test consisted of submaximal isokinetic knee extensions
      at an angular velocity of 1.57 rad x s(-1) for 45 s at the rate of 30
      contractions each min (submaximal work, Ws max) followed by 15-s maximal effort
      (maximal work, Wmax). Total duration of the test was 3 min. Haematocrit was
      measured and haemoglobin, ammonia, lactate, glucose and urea concentrations were
      analysed in blood samples obtained at rest and after cessation of muscle
      performance tests. The results indicated that creatine supplementation in
      comparison with placebo treatment during rapid body mass reduction may help to
      maintain muscle PT and W(PT)1 at high angular velocities, not influencing Wmax
      and the rate of fatigue development during Wmax, but affecting adversely Ws max.
      Within the limitations of the present study the reasons for the partially
      detrimental effect of creatine administration remain obscure, but it is suggested
      that impaired creatine uptake in muscle during body mass loss as well as creatine
      induced changes in muscle glucose and glycogen metabolism may be involved.

PMID- 9660162
TI  - Steroid hormone action 1998: novel challenges for drug design.

PMID- 9660163
TI  - On the road to understanding addiction.

PMID- 9660164
TI  - G protein-coupled receptors in silico.

PMID- 9660165
TI  - Ligand-independent activation of steroid hormone receptors.
AB  - In addition to the conventional hormone-dependent regulation of the activity of
      steroid/thyroid receptor family members, many studies have shown that there is
      substantial cross-talk between signal transduction pathways and steroid
      receptors. In a number of cases the modulation of kinase/phosphatase activity in
      cells leads to activation of steroid receptors in the absence of hormone. This
      novel mechanism may not be ubiquitous as the glucocorticoid receptor appears to
      be refractory to activation in the absence of hormone. However, estrogen
      receptors, progesterone receptors, androgen receptors, retinoic acid receptors,
      retinoid X receptors, and vitamin D receptors all exhibit ligand-independent
      activation under appropriate conditions. Whether a steroid receptor responds to a
      signal by inducing transcription of a target gene in the absence of hormone
      depends upon the cell type, promoter, and activator. The mechanism(s) by which
      ligand-independent activation is induced is currently a subject of great
      interest. Because the signals that activate receptors induce protein
      phosphorylation, altered phosphorylation of the receptors, and/or proteins that
      associate with the receptors are likely to be key to ligand-independent
      activation. In the case of the estrogen receptor there is good evidence that
      altered receptor phosphorylation plays a role in ligand-independent activation.
      Other likely targets are proteins in the heat shock protein complexes,
      corepressors, and/or coactivators of steroid receptors.

PMID- 9660166
TI  - Transcriptional cross-talk, the second mode of steroid hormone receptor action.
AB  - Physiological and therapeutic activities of glucocorticoids and other steroid
      hormones are mediated by the family of steroid hormone receptors. In addition to
      the classical mode of receptor action which involves binding as a dimer to
      regulatory sequences in target gene promoters and subsequent activation of
      transcription, a second mode of action is based predominantly on protein-protein
      interactions. As the paradigm of this so-called transcriptional cross-talk, the
      glucocorticoid receptor (GR) and the AP-1 transcription factor interact on target
      gene promoters which contain only a binding site for either one of the two
      transcription factors. Most frequently negative interference of both factors with
      each other's activity has been observed, for example, when AP-1 is composed of c
      Fos and c-Jun; however, synergism is also possible under cell-specific conditions
      and when AP-1 is a homodimer of c-Jun. Since the detection of the GR/AP-1 cross
      talk numerous other examples of transcription factor interactions have been
      described. Many members of the nuclear hormone receptor superfamily, including
      class II receptors, have been shown to participate in such cross-talk. Moreover,
      the transcription factor families of NF-kappaB/Rel as well as Stat, Oct, and
      C/EBP are engaged in cross-talk with steroid receptors. Despite the
      identification of a multitude of target genes which appear to be regulated by
      this type of transcription factor interaction, the exact molecular mechanism of
      the cross-talk has not yet been elucidated. This review discusses the current
      models to explain the molecular events of transcription factor cross-talk.
      Concepts are emphasized which suggest that the classical and the cross-talk mode
      of steroid receptor action can be triggered separately by the choice of specific
      ligands. A final section summarizes the partially contradictory data which assign
      a certain type of receptor action to a biological response particularly in the
      immune system.

PMID- 9660167
TI  - Targets of activated steroid hormone receptors: basal transcription factors and
      receptor interacting proteins.
AB  - Steroid hormone receptors constitute a family of inducible transcription factors
      that mediate the multi-fold effects of steroids on development, reproduction,
      proliferation, and cellular homeostasis. Activation through the binding of the
      cognate hormone enables the receptors to bind with high affinity to specific
      response elements in the promoters of target genes, resulting in stimulation or
      repression of transcription. While protein-protein interactions were early
      postulated to play an important role in the mechanism through which steroid
      hormone receptors exert their effects on transcription initiation, recent
      research has revealed a number of potential targets within the basal
      transcription machinery. Moreover, aided by the development of protein-protein
      interaction screening techniques, a rapidly increasing number of factors has been
      identified which associate with hormonally activated receptors and may be
      involved in the transactivation process. This review summarizes the basal
      transcription factors and cofactors which are targeted by steroid hormone
      receptors, describes their structure and properties, and discusses possible
      mechanisms.

PMID- 9660168
TI  - Exploring the role of sex steroids through studies of receptor deficient mice.
AB  - Decades of study have described a number roles fulfilled by the steroid hormones
      and their respective receptors in sexual differentiation and development,
      reproductive function and behavior, and more recently in the function and
      maintenance of non-reproductive organ systems, such as skeletal muscle, bone and
      coronary tissues. The biological effects of the steroid hormones are believed to
      be mediated in part by specific receptor proteins that demonstrated great
      specificity for their respective steroid ligands. Much of the experimental
      research of the functions of the sex steroid receptors has depended upon in vitro
      systems as well as in vivo methods that require surgical castration or the
      pharmacological administration of hormone antagonists. However, recently
      developed techniques that allow for manipulation of the mouse genome have been
      utilized to generate transgenic animals that lack functional estrogen or
      progesterone receptors. These transgenic animals, combined with the naturally
      existing Tfm mice which lack functional androgen receptor, now provide in vivo
      models for further study of the various actions of the sex steroids and their
      receptors. This review attempts to describe and compare the various phenotypes
      that result in each of these lines of mice, with emphasis on the development and
      function of the reproductive systems as well as reproductive behavior.

PMID- 9660169
TI  - Recent developments in molecular action of antihormones.
AB  - Antihormones are by definition antagonists of steroid hormone action. They
      interact with the ligand binding domains of steroid hormone receptors and
      competitively inhibit the action of the receptors by mechanisms that are not
      quite understood. In certain cases antihormones also exhibit agonistic activity
      especially in connection with certain naturally occurring receptor mutants. These
      observations together with findings of indiscriminate interaction of antihormones
      with several classes of steroid receptors have necessitated a search of more
      effective and reliable antihormones. Recent advances in the resolution of the
      crystal structure of the ligand binding domains of certain members of the steroid
      receptor family and identification of non-liganded activation of steroid
      receptors have produced considerable information that can be harnessed into a
      fruitful search for a new generation of antihormones.

PMID- 9660170
TI  - The human mu opioid receptor gene: 5' regulatory and intronic sequences.
AB  - The human mu opioid receptor (hMOR) interacts with endogenous and exogenous
      ligands to mediate its characteristic effects, reward, dependence, and analgesia.
      Specifically binding morphine, it represents the target of the most valuable pain
      killer in contemporary medicine. Analysis of its structure, regulation, and
      expression will elucidate molecular processes involved in opioid/morphine-induced
      actions. Thus we have contributed significant information on the genomic
      organization of hMOR, extending the previously known cDNA sequence information
      (2162 bp) up to a total of 6968 bp: we have determined 2412 bp of 5' regulatory
      region, identified one major and three minor transcription initiation sites 216,
      285, 358, and 373 bp upstream from the translation start codon, as well as
      potential binding sites for transcriptional regulatory factors, including
      putative cis-acting enhancer motifs for a glucocorticoid response element, cAMP
      response elements, activator proteins 1, and Yin Yang-1 boxes. Moreover, we have
      analyzed the 5' and 3' nucleotide sequences of introns 1 and 3 and the complete
      sequence of intron 2. In addition to the classical consensus sequences involved
      in RNA splicing, we have identified intronic repeats (A/T GGG) found to regulate
      alternative splicing, mutations of which cause human disease. A similar genetic
      variant is observed in the hMOR gene. Taken together, the sequence information
      presented will allow comprehensive analysis of this gene for allelic variations
      associated with vulnerability to drug abuse or individual differences in opiate
      mediated analgesia.

PMID- 9660171
TI  - Unchanged sarcoplasmic reticulum Ca2+-ATPase activity, reduced Ca2+ sensitivity,
      and negative force-frequency relationship in transgenic rats overexpressing the
      mouse renin gene.
AB  - Transgenic rats overexpressing the mouse Ren-2 gene [TG(mREN2)27 rats, TGR] were
      used to characterize alterations in force generation and relaxation following
      cardiac hypertrophy. Age-matched Sprague-Dawley rats were used as the control
      group. The beta-adrenoceptor dependent increase in force of contraction was
      reduced in the transgenic animals but not the Ca2+-dependent increase in force
      generation. Additionally, force of contraction decreased after increasing
      stimulation frequencies (up to 7 Hz), but the frequency-dependent decrease in
      force of contraction was significantly more pronounced in the transgenic group.
      The Ca2+ sensitivity in chemically skinned fiber preparations of TGR was reduced
      than that in Sprague-Dawley rats while maximum effectiveness was the same.
      Unexpectedly, the sarcoplasmic reticulum Ca2+-ATPase activity measured in crude
      membrane preparations from TGR did not differ from that in Sprague-Dawley rats;
      however, the activity of the Na+/K+-ATPase was less while the Na+/Ca2+-exchanger
      activity was significantly greater. In the same preparations the protein
      expression of SERCA2 was reduced in TGR while expression of phospholamban and
      calsequestrin remained the same. Thus in the model of cardiac hypertrophy
      harboring the mouse Ren-2 gene the hypothesized correlation between SERCA2
      function and force-frequency relationship was not observed. Possible reasons for
      the more negative force-frequency relationship in TGR included changes at the
      level of the myofilaments and altered intracellular Na+ homeostasis which may
      result from the reciprocal changes in the Na+/K+-ATPase and the Na+/Ca2+
      exchanger activity.

PMID- 9660172
TI  - Clamping down on clamps and clamp loaders--the eukaryotic replication factor C.
AB  - DNA transactions such as DNA replication and DNA repair require the concerted
      action of many enzymes, together with other proteins and non-protein cofactors.
      Among them three main accessory proteins, replication factor C (RF-C),
      proliferating-cell nuclear antigen (PCNA) and replication protein A (RP-A), are
      essential for accurate and processive DNA synthesis by DNA polymerases. RF-C is a
      complex consisting of five polypeptides with distinct functions. RF-C can bind to
      a template-primer junction and, in the presence of ATP, load the PCNA clamp onto
      DNA, thereby recruiting DNA polymerases to the site of DNA synthesis. RF-C not
      only acts as a clamp loader in DNA replication and DNA repair, but there is some
      evidence that it could be involved in several other processes such as
      transcription, S-phase checkpoint regulation, apoptosis, differentiation and
      telomere-length regulation.

PMID- 9660173
TI  - Sialic-acid-binding lectin from the slug Limax flavus--cloning, expression of the
      polypeptide, and tissue localization.
AB  - A cDNA library of Limax flavus was constructed and screened for sialic-acid
      specific lectins. Complementary DNA clones were categorized into seven groups
      corresponding to closely related but different sequences. Group 1 clones
      contained an ORF encoding 199 amino acids including a sequence identical to the
      partial amino acid sequence obtained from the lectin protein. Within its 1074-bp
      3' untranslated region, ten closely related 60-bp sequence repeats were found.
      Group 2 clones contained an ORF encoding a polypeptide chain of the same number
      of amino acid residues, with 89.1% overall identity to that of the group 1 and
      eight 60-bp repeat sequences in the 3' untranslated region. The remaining groups
      of clones contained ORF with highly similar full or partial sequences, with or
      without 60 bp repeats in the 3' untranslated region. The large number of closely
      related but different cDNA clones obtained indicated that the slug sialic-acid
      specific lectin gene is a member of a multigene family. The lectin amino acid
      sequence showed significant similarity with the fibrinogen domain of human
      tenascin-C, with a human C-type serum lectin, and with pig ficolin.
      Immunostaining analysis of slug tissue for the lectin indicated that it is
      present primarily on the epidermal surface and in mucous glands. Recombinant slug
      lectin protein lacking the 20-amino-acid N-terminal signal sequence produced in a
      bacterial expression system from a group-1 clone accumulated as aggregates in
      inclusion bodies, suggesting that large-scale production of the active agglutinin
      may be possible.

PMID- 9660174
TI  - Regulation of iron metabolism in the sanguivore lamprey Lampetra fluviatilis-
      molecular cloning of two ferritin subunits and two iron-regulatory proteins (IRP)
      reveals evolutionary conservation of the iron-regulatory element (IRE)/IRP
      regulatory system.
AB  - Two ferritin cDNAs were cloned from the liver and spinal cord of the sanguivore
      lamprey Lampetra fluviatilis, an extant representative of the ancient agnathan
      (jawless) stage in vertebrate evolution. The deduced proteins of 20.2 kDa (H
      subunit) and 20.1 kDa (M-subunit) display 73% sequence identity, and both contain
      the ferroxidase center characteristic of animal H-ferritin. A highly conserved
      iron-responsive element (IRE) was identified in the 5' untranslated region of
      lamprey H-ferritin. Lamprey ferritin IRE forms a specific complex with crude
      lamprey and rat liver extracts, and with recombinant human iron-regulatory
      protein (IRP-1) in an electrophoretic mobility shift assay. Furthermore, lamprey
      ferritin IRE competes with labeled human ferritin IRE for binding to IRP in
      lamprey and mammalian extracts. Two liver cDNA sequences encoding 323 residues
      and 101 residues of two genetically distinct lamprey IRP were amplified by PCR.
      Lamprey IRP-1 and IRP-2, which are 72% identical, display about 74% sequence
      identity to their presumed homologues in mammals. Northern blot analysis shows
      that two IRP transcripts of 3.6 kb and 5.8 kb are expressed in lamprey liver.
      Given the ancient lineage of lampreys, the results indicate that the IRE/IRP
      regulatory system has remained highly conserved during the evolution of
      vertebrates.

PMID- 9660175
TI  - Iron-regulatory protein-1 (IRP-1) is highly conserved in two invertebrate species
      -characterization of IRP-1 homologues in Drosophila melanogaster and
      Caenorhabditis elegans.
AB  - Iron-regulatory protein-1 (IRP-1) plays a dual role as a regulatory RNA-binding
      protein and as a cytoplasmic aconitase. When bound to iron-responsive elements
      (IRE), IRP-1 post-transcriptionally regulates the expression of mRNAs involved in
      iron metabolism. IRP have been cloned from several vertebrate species. Using a
      degenerate-primer PCR strategy and the screening of data bases, we now identify
      the homologues of IRP-1 in two invertebrate species, Drosophila melanogaster and
      Caenorhabditis elegans. Comparative sequence analysis shows that these
      invertebrate IRP are closely related to vertebrate IRP, and that the amino acid
      residues that have been implicated in aconitase function are particularly highly
      conserved, suggesting that invertebrate IRP may function as cytoplasmic
      aconitases. Antibodies raised against recombinant human IRP-1 immunoprecipitate
      the Drosophila homologue expressed from the cloned cDNA. In contrast to
      vertebrates, two IRP-1 homologues (Drosophila IRP-1A and Drosophila IRP-1B),
      displaying 86% identity to each other, are expressed in D. melanogaster. Both of
      these homologues are distinct from vertebrate IRP-2. In contrast to the mammalian
      system where the two IRP (IRP-1 and IRP-2) are differentially expressed,
      Drosophila IRP-1A and Drosophila IRP-1B are not preferentially expressed in
      specific organs. The localization of Drosophila IRP-1A to position 94C1-8 and of
      Drosophila IRP-1B to position 86B3-6 on the right arm of chromosome 3 and the
      availability of an IRP-1 cDNA from C. elegans will facilitate a genetic analysis
      of the IRE/IRP system, thus opening a new avenue to explore this regulatory
      network.

PMID- 9660176
TI  - Two distinct structures of alpha-conotoxin GI in aqueous solution.
AB  - The detailed analysis of conformational space of alpha-conotoxin GI in aqueous
      solution has been performed on the basis of two-dimensional NMR spectroscopy data
      using multiconformational approach. As the result, two topologically distinct
      interconvertible sets of GI conformations (populations of 78% and 22%) have been
      found. A common feature of the two sets is the Asn4-Cys7 beta-turn. The Gly8 to
      Tyrll region has a structure of right-handed helical turn in the major set and
      two sequential bends in the minor one. N-terminus and C-terminus also have
      different orientations, anti-parallel in the major conformational set and
      parallel in the minor one. An average pairwise rmsd for backbone heavy atoms is
      0.56 A in the major set, 0.23 A in the minor, and 1.85 A between the structures
      of the two sets. The X-ray structure of GI [Guddat, L. W., Martin, J. A., Shan,
      L., Edmundson, A. B. & Gray, W. R. (1996) Biochemistry 35, 11329 - 11335] has the
      same folding pattern as the major NMR set, the average backbone rmsd between the
      two structures being 0.77 A.

PMID- 9660177
TI  - RNase L inhibitor (RLI) antisense constructions block partially the down
      regulation of the 2-5A/RNase L pathway in encephalomyocarditis-virus-(EMCV)
      infected cells.
AB  - The interferon-(IFN)-inducible 2',5'-oligoadenylate (2-5A)/endoribonuclease L
      (RNase L) pathway plays a major role in the antiviral and antiproliferative
      effects of IFN. The 2-5A/RNase L pathway appears to be regulated by the cell
      growth status or viral infection. Viruses, and picornaviruses in particular, have
      evolved strategies to escape the 2-5A/RNase L-pathway-associated antiviral
      activity. We have recently cloned a cDNA coding for RLI, a RNase-L-specific
      protein inhibitor. Its regulated expression by viral infection could provide a
      new strategy to modulate the 2-5A/RNase L pathway. Since RNase L had been shown
      to be down regulated upon encephalomyocarditis (EMCV) infection, we stably
      transfected HeLa cells with a RLI antisense cDNA expressing vector. Four
      independent clones named VAS1, VAS2, VAS3 and VAS4 and one clone transfected with
      the empty vector (VV) as control, were analyzed. The level of RLI was decreased
      by 20% for VAS1, 25% for VAS2, 75% for VAS3 and 50% for VAS4. The inactivation of
      RNase L observed during EMCV infection was decreased in these clones as compared
      to control HeLa cells. Here again the results vary between the four clones. The
      maximum inhibition of RNase L (90%) was observed in control cells and in VAS1
      while 48% inhibition was observed in VAS4 and 25% in VAS3. The reversal in RNase
      L inhibition thus reflects closely the resulting RLI level, in keeping with a
      major role of RLI in EMCV-induced down regulation of 2-5A-binding activity of
      RNase L. Moreover, cells expressing a low level of RLI (VAS3 and VAS 4) are
      partially resistant to EMCV infection.

PMID- 9660178
TI  - Nitrone spin traps and their pyrrolidine analogs in myocardial reperfusion
      injury: hemodynamic and ESR implications--evidence for a cardioprotective
      phosphonate effect for 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline N-oxide in rat
      hearts.
AB  - Formation of free radicals during reperfusion of the isolated ischemic heart has
      often been demonstrated by detecting hydroxyl radical spin adducts of the nitrone
      5,5-dimethyl-1-pyrroline N-oxide (DMPO) in coronary effluents. However, questions
      still remain regarding (a) whether the reported cardiovascular effects of nitrone
      perfusion may affect the formation of spin adducts, and (b) the primary
      generation of superoxide (O2.-), because of the short persistency of O2.-/DMPO
      spin adduct. We therefore compared the effects of perfusing 5 mM of two nitrones,
      DMPO and 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline N-oxide (DEPMPO) or the two
      structurally related pyrrolidines, diethyl (2-methyl-2-pyrrolidinyl) phosphonate
      (DEPMPH) and pyrrolidine (PyH), on postischemic functional recovery of rat hearts
      subjected to 10 min of low-flow ischemia, 30 min of global ischemia and 60 min of
      reperfusion. All compounds were added to the perfusate before ischemia,
      throughout low-flow ischemia and during the initial 10 min of reflow. In one
      additional group, hearts received DEPMPO only at reflow. Hemodynamic and in vitro
      ESR evidence is presented indicating that the phosphonate group of DEPMPO and
      DEPMPH confers these molecules with an enhanced cardioprotective efficacy,
      unrelated to radical scavenging, acting in synergy with the intrinsic radical
      trapping effects of the nitronyl group. Continuous-flow ESR spin trapping using
      5.7 mM DEPMPO administered at reflow, but not before ischemia, demonstrated for
      the first time extended formation of O2.- in the reperfused myocardium.

PMID- 9660179
TI  - Suppression of decorin expression and partial induction of anchorage-independent
      growth by the v-src oncogene in human fibroblasts.
AB  - To determine its role in cell transformations, the v-src oncogene was introduced
      into the human foetal diploid fibroblasts MRC-5 and into MRC-SV1, a simian virus
      40 (SV40)-transformed cell line derived from them. Infected cells were found to
      contain stably integrated intact proviruses, as determined by Southern blot
      analysis. Although highly expressed, v-src did not change the morphology or
      growth patterns of MRC-5 cells and failed to induce foci or alter their
      saturation densities. However, overexpression of v-src reduced the plating
      efficiencies of MRC-5 and induced anchorage-independent growth in a low but
      significant number of cells. Northern blot analysis showed that v-src selectively
      abolished the expression of decorin, a small dermatan/chondroitin sulphate
      proteoglycan that interacts with extracellular-matrix components and modulates
      collagen-fibril formation and the activity of transforming growth factor (TGF)
      beta1. Addition of herbimycin A, a potent pp60src tyrosine-kinase inhibitor,
      resulted in the reexpression of decorin in MRC-5 carrying v-src. There were no
      changes in the expressions of fibronectin, procollagen type I, or tissue
      plasminogen activator, an activator of extracellular-matrix-degrading enzymes.
      Moreover, v-src did not alter the expressions of the epidermal-growth-factor
      receptor or TGFbeta1 or reduce the growth-factor requirements of MRC-5
      fibroblasts. MRC-5 and MRC-SV1 expressing v-src remained non-tumourigenic when
      injected into nude mice. Constitutive expression of v-src did not alter the mRNA
      levels of c-jun and junB, suggesting that the effects of the oncogene are not
      mediated by AP-1. Decorin gene expression has been shown previously to be maximal
      in quiescent cells and virtually absent in transformed ones. Our data indicate
      that the ability to synthesise decorin can be suppressed in human fibroblasts
      without their becoming transformed, and that the relations between decorin
      synthesis and growth controls need further clarification.

PMID- 9660180
TI  - Calcitriol and transforming growth factor-beta upregulate 5-lipoxygenase mRNA
      expression by increasing gene transcription and mRNA maturation.
AB  - Differentiation of the human monocytic cell line Mono Mac 6 with calcitriol plus
      transforming growth factor-beta (TGFbeta) strongly induces 5-lipoxygenase (5-LO)
      mRNA and protein expression. The mechanism of 5-LO mRNA induction by these agents
      was investigated. Analysis of mature 5-LO mRNA by reverse-transcriptase-PCR gave
      a 42-fold induction which was not due to alterations in 5-LO half life and which
      was only in part due to an induction of gene transcription. There was an up to
      fivefold increase in 5-LO primary transcripts by TGFbeta and calcitriol, which
      could be inhibited by cycloheximide. No significant effects on 5-LO transcription
      were observed with TGFbeta or calcitriol alone. However, treatment of the cells
      with either calcitriol or TGFbeta and addition of the corresponding second
      inducer lead to an about fourfold induction of primary transcript levels.
      Addition of cycloheximide together with the second inducer inhibited only the
      TGFbeta but not the calcitriol effects, which indicated that there is a direct
      stimulation of 5-LO transcription by calcitriol in the presence of TGFbeta
      induced proteins. In order to investigate the effects of TGFbeta/calcitriol on 5
      LO transcript, elongation and maturation, the relative changes in immature and
      mature 5-LO RNA species were analyzed by reverse-transcription-PCR. Analysis of
      exons 1-5 indicated an about threefold induction of 5-LO transcripts by
      calcitriol/TGFbeta, respectively. However, when exons 6-14 were determined, more
      pronounced increments were found (3.6-12-fold). Selective analysis of
      polyadenylated and spliced 5-LO mRNA species gave a 42-fold induction. The
      effects of both TGFbeta and calcitriol on transcript elongation and maturation
      were inhibited by cycloheximide. Our results show that induction of 5-LO mRNA by
      calcitriol and TGFbeta is due to a modest increase in 5-LO gene transcription and
      to the stimulation of transcript elongation and maturation.

PMID- 9660181
TI  - Clusterin overexpression in rat pancreas during the acute phase of pancreatitis
      and pancreatic development.
AB  - Molecular mechanisms associated with apoptosis in pancreas remain largely
      unknown. Clusterin mRNA is induced in several tissues in response to most
      apoptotic stimuli. In these tissues, clusterin has an antiapoptotic activity. The
      aim of this work was to test whether clusterin, which is not expressed in normal
      pancreas, was induced in pancreas during pancreatitis and pancreatic development.
      Clusterin mRNA levels were strongly increased 6 h after pancreatitis induction.
      Maximal expression happened between 24-48 h and decreased progressively to
      undetectable levels at day 5. Clusterin mRNA was expressed with similar intensity
      in oedematous caerulein-induced pancreatitis and in response to various degrees
      of necrohaemorrhagic taurocholate-induced pancreatitis, indicating a maximal gene
      activity in all types of pancreatitis; in situ hybridization showed that the
      acinar cells and some ducts expressed clusterin mRNA. A single band of about 35
      38 kDa was detected by western blot in pancreatic homogenates and in pancreatic
      juice from rats with acute pancreatitis, but not from control rats. Clusterin
      mRNA expression was strong in late fetal life and remains high until day 11 post
      partum, then decreased progressively with a minimum from 35 to 90 days post
      partum. Clusterin mRNA levels were strongly induced in pancreatic acinar AR4-2J
      cells in response to various apoptotic stimuli (i.e., cycloheximide,
      staurosporine, ceramide and H2O2) but not with interleukin (IL)-1, IL-4 or IL-6
      or heat shock, which do not induce apoptosis in AR4-2J cells. In conclusion, we
      demonstrated that clusterin is synthesized and released by the pancreas. Its
      strong expression during acute pancreatitis suggests its involvement in the
      pancreatic response to injury. Clusterin is also induced during pancreatic
      development. Because these situations are associated with apoptosis and clusterin
      was shown to protect against apoptosis, we speculate that clusterin could be
      involved in the control of acinar cell apoptosis.

PMID- 9660182
TI  - Cloning, sequencing, temporal expression and tissue-specificity of two serine
      proteases from the midgut of the blood-feeding fly Stomoxys calcitrans.
AB  - Using highly degenerate, serine-protease-specific PCR primers on a midgut
      specific cDNA library it was estimated that a minimum of 24 independent serine
      proteases were expressed in the midgut of Stomoxys calcitrans. The relative
      abundance of these 24 independent serine proteases has been estimated by
      restriction analysis of PCR products, showing that 69% fall into six almost
      equally abundant groups. Two highly abundant serine protease cDNAs (Ssp1 and
      Ssp2) were isolated and sequenced. They encode preproenzymes of 272 amino acids
      (Mr 28521) and 255 amino acids (Mr 27097) with putative signal peptides of 17
      amino acids and 16 amino acids, putative activation peptides of 15 amino acids
      and 10 amino acids and mature enzymes of 239 amino acids (Mr 25322; pI 4.89) and
      228 amino acids (Mr 24182; pI 7.59), respectively. Both deduced amino acid
      sequences contain the Asp/His/Ser catalytic triad and the highly conserved
      sequences surrounding it. Ssp2 also has the aspartate and two glycine residues in
      the specificity pocket, marking this as a typical trypsin. The positioning of the
      residues in the specificity pocket of Sspl is unusual; aspartate and glycine
      residues are present, which is typical of trypsin, but both are separated from
      surrounding conserved residues by additional amino acids; the second glycine
      found in the specificity pocket of trypsin is replaced by a serine, which is
      typical of chymotrypsin. Although a serine protease, the precise substrate
      specificity of Sspl remains to be determined. Northern analysis shows that both
      serine proteases are expressed constitutively with only a 20% change in the
      levels of expression of Ssp1 and Ssp2 through the digestive cycle, and that
      expression occurs predominantly in the opaque region of the midgut, the region
      responsible for secretion of digestive enzymes.

PMID- 9660183
TI  - The gene for the human Src-like adaptor protein (hSLAP) is located within the 64
      kb intron of the thyroglobulin gene.
AB  - In this study, we describe the molecular cloning and characterization of a Src
      like adaptor protein gene embedded within the genomic organization of the human
      thyroglobulin (Tg) gene. This gene was identified by exon trapping on overlapping
      cosmids encompassing the largest Tg intron. A 2.6-kb transcript, with the highest
      levels of expression in fetal brain and lung, was detected on Northern blots. Two
      full-length cDNAs (one alternatively spliced) were isolated from a fetal brain
      library, both containing an open reading frame of 276 amino acids, but lacking a
      catalytic tyrosine kinase domain. The gene shows a high degree of cross-species
      similarity and appears to be transcribed in the direction opposite to Tg. This
      gene, designated hslap, appears to be the human ortholog of the recently
      described gene for the murine Src-like adaptor protein (mSLAP), a candidate
      intermediate in the signal-transduction pathway of the Eck receptor tyrosine
      kinase. Human slap is located in the candidate region for a recessive
      demyelinating neuropathy on chromosome 8q24, but sequence analysis failed to
      identify mutations, suggesting that it is not the gene for this disease.

PMID- 9660184
TI  - Structure, organization and expression of two clustered cuticle protein genes
      during the metamorphosis of an insect, Tenebrio molitor.
AB  - A 4-kb DNA segment of Tenebrio molitor (Insecta, Coleoptera) genomic DNA
      containing two larval-pupal cuticular genes has been cloned and sequenced. These
      genes, transcribed in opposite directions, are related in DNA sequence and the
      proteins encoded are very similar. Each of them contains a single intron located
      inside the sequence encoding the signal peptide, and a conserved sequence at -200
      bp from the mRNA start position. These similarities in sequence suggest that
      these genes have evolved by duplication followed by diversification and that they
      are members of a family of genes with a common ancestry. They are the first
      example of clustered genes in Tenebrio molitor.

PMID- 9660185
TI  - NMR studies on the structure/function correlations of T-cell-epitope analogs from
      pertussis toxin.
AB  - A synthetic tridecapeptide, corresponding to the 30-42 fragment of the S1 subunit
      of pertussis toxin, has been structurally characterised by using NMR
      spectroscopy. The molecule corresponds to a T-cell epitope of the bacterial toxin
      which has been extensively analysed with the alanine scanning approach to check
      the relevance of each residue for the biological activity of the peptide. Five of
      these Ala-substituted analogs have also been spectroscopically studied. In the
      experimental conditions used, different extents of helicity were found for the
      six peptides in a way which cannot be related to their capabilities of of binding
      to major histocompatibility complex (MHC) class II and inducing T-cell
      proliferation. Backbone flexibility around helical transient conformations seems
      to constitute the structural intermediate step between the structure of the
      corresponding sequence within the parental protein and in the MHC class II
      complex. A model of the latter complex, which accounts for the different
      biological activities of the analogs, is proposed.

PMID- 9660186
TI  - Subtypes of odorant-binding proteins--heterologous expression and ligand binding.
AB  - Odorant-binding proteins (OBP) in the mucus of the olfactory epithelium are
      thought to transfer the hydrophobic odorous compounds through the aqueous barrier
      towards the chemo-sensory cells. To evaluate their binding properties, two
      distinct OBP subtypes of the rat were expressed as N-terminal His-tagged fusion
      proteins in Escherichia coli, thus allowing an efficient purification. Based on
      gel chromatography and CD spectroscopy analysis the recombinant OBP subtypes seem
      to share several structural features with other members of the lipocalin family.
      Approaches to elucidate whether heterologous expressed OBPs interact with odorous
      compounds revealed that OBP1 specifically binds 2-[3H]-isobutyl-3-methoxypyrazine
      whereas OBP2 did not shown any specific binding to this compound. In contrast,
      the chromophore 1-anilinonaphthalene 8-sulfonic acid (1,8-ANS) specifically
      interacted with OBP2 but not with OBP1. Displacement experiments monitored by the
      relative fluorescence intensity revealed that fatty acids with appropriate chain
      length act as efficient competitors. Some odorous compounds, notably lilial (p
      tert-butyl-alpha-methyl dihydrocinnamic aldehyde) and citralva (3,7-dimethyl-2,6
      octadienenitrile), also displaced efficiently the chromophore, whereas pyrazine
      derivatives including 2-isobutyl-3-methoxypyrazine and other odorants did not.
      These results indicate that rat OBPs have distinct ligand specificities.

PMID- 9660187
TI  - A family of flavoproteins in the domains Archaea and Bacteria.
AB  - A family of flavoproteins, called A-type flavoproteins, is described. It consists
      of 14 protein sequences of 385-597 amino acids in length, 7 from methanogens
      (domain: Archaea), 5 from phototrophic prokaryotes, one from Escherichia coli,
      and a partial sequence from the sulfate reducer Desulfovibrio gigas (domain:
      Bacteria). No similar sequence could be found in the domain Eucarya. All
      sequences show significant similarity over a 385-400 amino acid portion
      overlapping a recognizable flavodoxin signature starting at positions 245-285 of
      the common core sequence. Cofactor analysis and, to some extent, analysis of the
      primary structure of six A-type flavoproteins, three of which are structurally
      characterized here, support the existence of four sub-families: (a) simple
      flavoproteins binding only FMN; (b) diflavin flavoproteins binding FMN and FAD;
      (c) a flavorubredoxin binding FMN and iron; (d) a hemoflavoprotein. The possible
      involvement of A-type flavoproteins in the metabolism of oxygen, as suggested for
      D. gigas hemoflavoprotein [Gomes, C. M., Silva, G., Oliveira, S., LeGall, J.,
      Liu, M.-Y., Xavier, A. V., Rodrigues-Pousada, C. & Teixeira, M. (1997) J. Biol.
      Chem. 272, 22502-22508], is discussed.

PMID- 9660188
TI  - Structural basis of the chiral selectivity of Pseudomonas cepacia lipase.
AB  - To investigate the enantioselectivity of Pseudomonas cepacia lipase, inhibition
      studies were performed with Sc- and Rc-(Rp,Sp)-1,2-dialkylcarbamoylglycero-3-O-p
      nitrophenyl alkylphosphonates of different alkyl chain lengths. P. cepacia lipase
      was most rapidly inactivated by Rc-(Rp,Sp)-1,2-dioctylcarbamoylglycero-3-O-p
      nitrophenyl octylphosphonate (Rc-trioctyl) with an inactivation half-time of 75
      min, while that for the Sc-(Rp,Sp)-1,2-dioctylcarbamoylglycero-3-O-p-nitrophenyl
      octyl-phosphonate (Sc-trioctyl) compound was 530 min. X-ray structures were
      obtained of P. cepacia lipase after reaction with Rc-trioctyl to 0.29-nm
      resolution at pH 4 and covalently modified with Rc-(Rp,Sp)-1,2
      dibutylcarbamoylglycero-3-O-p-nitrophenyl butyl-phosphonate (Rc-tributyl) to
      0.175-nm resolution at pH 8.5. The three-dimensional structures reveal that both
      triacylglycerol analogues had reacted with the active-site Ser87, forming a
      covalent complex. The bound phosphorus atom shows the same chirality (Sp) in both
      complexes despite the use of a racemic (Rp,Sp) mixture at the phosphorus atom of
      the triacylglycerol analogues. In the structure of Rc-tributyl-complexed P.
      cepacia lipase, the diacylglycerol moiety has been lost due to an aging reaction,
      and only the butyl phosphonate remains visible in the electron density. In the Rc
      trioctyl complex the complete inhibitor is clearly defined; it adopts a bent
      tuning fork conformation. Unambiguously, four binding pockets for the
      triacylglycerol could be detected: an oxyanion hole and three pockets which
      accommodate the sn-1, sn-2, and sn-3 fatty acid chains. Van der Waals'
      interactions are the main forces that keep the radyl groups of the
      triacylglycerol analogue in position and, in addition, a hydrogen bond to the
      carbonyl oxygen of the sn-2 chain contributes to fixing the position of the
      inhibitor.

PMID- 9660189
TI  - Cobalamin (vitamin B12) biosynthesis--cloning, expression and crystallisation of
      the Bacillus megaterium S-adenosyl-L-methionine-dependent cobalt-precorrin-4
      transmethylase CbiF.
AB  - The Bacillus megaterium cbiF, encoding the cobalt-precorrin-4 S-adenosyl-L
      methionine-dependent transmethylase of the anaerobic cobalamin biosynthetic
      pathway, has been cloned and overexpressed as a His-tagged recombinant protein in
      Escherichia coli. The protein was purified to homogeneity by a combination of
      metal chelate chromatography and high-resolution anion-exchange chromatography.
      The protein migrated with a subunit mass of 31 kDa by SDS/PAGE and with a
      molecular mass of 62 kDa by analytical gel filtration, suggesting that the native
      recombinant protein is a homodimer. The His-tagged protein was physiologically
      active as it was able to complement a Salmonella typhimurium cbiF mutant.
      However, the protein did not bind S-adenosyl-L-methionine with the same avidity
      as observed with other corrin biosynthetic transmethylases. A crystallisation
      screen of the purified protein led to the identification of two discrete crystal
      forms. One of these forms has been characterised and a full data set collected.

PMID- 9660190
TI  - The Streptomyces tendae Tu901 L-lysine 2-aminotransferase catalyzes the initial
      reaction in nikkomycin D biosynthesis.
AB  - Protein P8 was previously identified as a putative nikkomycin biosynthesis
      protein. The gene (nikC) encoding protein P8 was cloned from the Streptomyces
      tendae Tu901 nikkomycin gene cluster and sequenced. The nikC gene was inactivated
      by inserting a kanamycin resistance cassette; the mutant did not produce the
      biologically active nikkomycins I, J, X, and Z, but accumulated the nucleoside
      moieties nikkomycins C(X) and C(Z). The mutant was complemented to nikkomycin
      production (I, J, X, Z) by nikC expressed from the mel promoter of the vector
      pIJ702. Furthermore, the nikkomycin-negative phenotype was reversed by the
      addition of picolinic acid, a precursor of the peptidyl moiety of nikkomycins
      (nikkomycin D), into the culture medium. The nikC gene was expressed in
      Escherichia coli and identified and characterized at the enzyme level. NikC
      encodes an L-lysine 2-aminotransferase, and the activity was exclusively detected
      in nikkomycin producers and its presence correlated to nikkomycin production. The
      nikC-inactivated mutant grew with L-lysine as sole source of nitrogen and carbon,
      indicating that L-lysine 2-aminotransferase is not required for lysine
      catabolism. Our results identified the nikC-encoded L-lysine 2-aminotransferase
      as the nikkomycin biosynthetic enzyme that catalyzes the initial reaction in
      nikkomycin D biosynthesis. The NikC protein belongs to a novel family of
      pyridoxamine or pyridoxal-phosphate-dependent dehydrases and aminotransferases,
      some of which are involved in dideoxy- and deoxyaminosugar biosynthesis.

PMID- 9660191
TI  - Purification and characterization of an alcohol dehydrogenase from the Antarctic
      psychrophile Moraxella sp. TAE123.
AB  - An NAD+-dependent alcohol dehydrogenase (ADH) of the Antarctic psychrophile
      Moraxella sp. TAE123 was purified to homogeneity with an overall yield of 16.7%
      and further characterized. The native enzyme had an apparent molecular mass of
      240 kDa and consisted of four identical 52-kDa subunits. The pI of the enzyme was
      determined to be 5.5, while its optimum pH is 7.5. The enzyme contained 1 zinc
      atom/subunit and exhibited a remarkable thermal lability. Moraxella sp. TAE123
      ADH exhibited a wide range of substrate specificity similar to its mammalian
      counterparts and in contrast to other microbial ADHs. It oxidized mainly primary
      and secondary aliphatic alcohols. The highest reaction rate was observed when
      ethanol was used as substrate. A gradual decrease in rate was observed by
      increasing the length and branching of the carbon chain of the alcohol. This
      enzyme oxidized effectively large bulky alcohols, such as diphenylmethanol.
      Reduction of aldehydes and ketones was also observed. N-terminal amino acid
      sequence analysis of the enzyme did not reveal any similarity with the amino
      termini of all other ADHs, while an unexpected significant similarity was
      observed with the amino terminal sequence of four prokaryotic aldehyde
      dehydrogenases.

PMID- 9660192
TI  - Do ATP4- and Mg2+ bind stepwise to the F1-ATPase of Halobacterium saccharovorum?
AB  - It is commonly believed that MgATP2- is the substrate of F1-ATPases and ATP4-
      acts as a competitive inhibitor. However, the velocity equation for such
      competitive inhibition is equivalent to that for a rapid equilibrium ordered
      binding mechanism in which ATP4- adds first and the binding of Mg2+ is dependent
      on the formation of the E x ATP4- complex. According to this ordered-binding
      model, solution formed MgATP2- is not recognized by the ATPase as a direct
      substrate, and the high-affinity binding of Mg2+ to the E x ATP4- complex is the
      key reaction towards the formation of the ternary complex. These models (and
      others) were tested with an F1- ATPase, isolated from Halobacterium
      saccharovorum, by evaluating the rate of ATP hydrolysis as a function of free
      [ATP4-] or free [Mg2+]. The rates were asymmetrical with respect to increasing
      [ATP4-] versus increasing [Mg2+]. For the ordered-binding alternative, a series
      of apparent dissociation constants were obtained for ATP4-(K(A)aPP), which
      decreased as [Mg2+] increased. From this family of K(A)aPP the true K(A) was
      retrieved by extrapolation to [Mg2+] = 0 and was found to be 0.2 mM. The
      dissociation constants for Mg2+, established from these experiments, were also
      apparent (K(B)aPP) and dependent on [ATP4-] as well as on the pH. The actual K(B)
      was established from a series of K(B)aPP by extrapolating to [ATP4-] = infinity
      and to the absence of competing protons, and was found to be 0.0041 mM. The pKa
      of the protonable group for Mg2+ binding is 8.2. For the competitive inhibition
      alternative, rearrangement of the constants and fitting to the velocity equation
      gave an actual binding constant for MgATP2- (K(EAB)) of 0.0016 mM and for ATP4-
      (K(EA)) of 0.2 mM. Decision between the two models has far-reaching mechanistic
      implications. In the competitive inhibition model MgATP2- binds with high
      affinity, but Mg2+ cannot bind once the E x ATP4- complex is formed, while in the
      ordered-binding model binding of Mg2+ requires that ATP4- adds first. The steric
      constraints evident in the diffraction structure of the ATP binding site in the
      bovine mitochondrial F-ATPase [Abrahams, J. P., Leslie, A. G. W., Lutter, R. &
      Walker, J. E. (1994) Nature 370, 621-628] tend to favor the ordered-binding
      model, but the final decision as to which kinetic model is valid has to be from
      further structural studies. If the ordered-binding model gains more experimental
      support, a revision of the current concepts of unisite catalysis and negative
      cooperativity of nucleotide binding will be necessary.

PMID- 9660193
TI  - Changes in glycosaminoglycan structure and composition of the main heparan
      sulphate proteoglycan from human colon carcinoma cells (perlecan) during cell
      differentiation.
AB  - Colon carcinoma cells provide a useful model to study the biochemical processes
      associated with cell differentiation. Undifferentiated HT29, differentiated
      HT29MTX(-3) and HT29MTX(-6), and Caco2 human colon carcinoma cells have been used
      to study the production of proteoglycans and to characterize the
      glycosaminoglycan structure of the heparan sulphate chains. All the cell lines
      produce mainly a heparan sulphate proteoglycan that is found partly in the
      extracellular medium and associated to the cell membrane. The heparan sulphate
      proteoglycans from the media were purified by ion-exchange chromatography and
      subjected to structural analysis. The heparan sulphate proteoglycan from
      differentiated cells is larger and more homogeneous in size than the heparan
      sulphate proteoglycan from undifferentiated HT29 cells. No differences in protein
      core structure were observed when cells were labeled with [35S]methionine and the
      protein cores visualized by gel electrophoresis. Nevertheless, differences in
      glycosaminoglycan composition were found correlated with the degree of
      differentiation. The heparan sulphate chains from differentiated HT29MTX(-3) and
      HT29MTX(-6) cells have a higher sulphation degree than those from
      undifferentiated HT29 cells. The heparan sulphate from Caco2 cells is the most
      highly sulphated species. The differences are mainly attributed to O-sulphate
      groups. The increase in O-sulphation was more pronounced for D-glucosamine 6-O
      sulphate than for L-iduronic acid 2-O-sulphate groups.

PMID- 9660194
TI  - Structural studies of the O-antigenic polysaccharide from Escherichia coli O139.
AB  - The structure of the O-antigenic polysaccharide from Escherichia coli O139 has
      been investigated with the aid of NMR spectroscopy, and sugar and methylation
      analyses. The sequence of the sugar residues was determined by NOESY and
      heteronuclear-multiple-bond-connectivity NMR experiments. The polysaccharide is
      composed of heptasaccharide repeating units containing 0.6 mol O-acetyl
      groups/repeating unit. The following structure is concluded, where Rha represents
      rhamnose. [structure in text]

PMID- 9660195
TI  - Control by ATP and ADP of voltage-induced mammalian-cell-membrane
      permeabilization, gene transfer and resulting expression.
AB  - We have permeabilized and transfected mammalian cells by transient alteration of
      their native transmembrane electrical potential difference. Chinese hamster ovary
      cells were chosen as a model in order to study the electropermeabilization and
      electrotransfection processes. Propidium iodide was used to monitor
      permeabilization. A plasmid carrying the beta-galactosidase gene was used to
      follow direct gene transfer and expression by determining transient expression of
      the electrotransfered activity at the single-cell level. The effect of
      nucleotides on cell permeabilization and transfection was studied by altering the
      cytosolic ATP and ADP contents of cells either during the pulsation or during the
      period following it. Permeabilization and transfection are not regulated in the
      same way by the ATP and ADP levels. The permeabilization efficiency remains
      unaffected. Cell viability and the transfection yield are dramatically affected.
      While ADP is involved in the step of DNA transfer across the electropermeabilized
      plasma membrane, ATP controls other steps (cytoplasmic DNA migration towards the
      nucleus, expression). Our results prove, firstly, that membrane resealing is
      required but is not sufficient to preserve cell viability and, secondly, that
      transfection is a cell-mediated process and not only an electrophoretic step
      driven by the external field.

PMID- 9660196
TI  - Assembly of cytochrome-c oxidase in cultured human cells.
AB  - The assembly of cytochrome-c oxidase was studied in human cells cultured in the
      presence of inhibitors of mitochondrial or cytosolic protein synthesis.
      Mitochondrial fractions were resolved using two-dimensional PAGE (blue native
      PAGE and tricine/SDS/PAGE) and subsequent western blots were developed with
      monoclonal antibodies against specific subunits of cytochrome-c oxidase. Proteins
      were also visualized using metabolic labeling followed by two-dimensional
      electrophoresis and fluorography. These techniques allowed identification of two
      assembly intermediates of cytochrome-c oxidase. Assembly of the 13 subunits of
      cytochrome-c oxidase starts with the association of subunit I with subunit IV.
      Then a larger subcomplex is formed, lacking only subunits VIa and either VIIa or
      VIIb.

PMID- 9660197
TI  - Biochemical and genetic characterization of the membrane-associated malate
      dehydrogenase (acceptor) from Corynebacterium glutamicum.
AB  - In addition to a cytoplasmic, NAD-dependent malate dehydrogenase (EC 1.1.1.37),
      Corynebacterium glutamicum possesses a highly active membrane-associated malate
      dehydrogenase (acceptor) (EC 1.1.99.16). This enzyme also takes part in the
      citric acid cycle. It oxidizes L-malate to oxaloacetate and donates electrons to
      ubiquinone-1 and other artificial acceptors or, via the electron transfer chain,
      to oxygen. NAD is not an acceptor and the natural direct acceptor for the enzyme
      is most likely a quinone. The enzyme is therefore called malate:quinone
      oxidoreductase, abbreviated to Mqo. Mqo is a peripheral membrane protein and can
      be released from the membrane by addition of chelators. The solubilized form was
      partially purified and characterized biochemically. FAD is probably a tightly but
      non-covalently bound prosthetic group, and the enzyme is activated by lipids. A
      C. glutamicum mutant completely lacking Mqo activity was isolated. It grows
      poorly on several substrates tested. The mutant possesses normal levels of
      cytoplasmic NAD-dependent malate dehydrogenase. A plasmid containing the gene
      from C. glutamicum coding for Mqo was isolated by complementation of the Mqo
      negative phenotype. It leads to overexpression of Mqo activity in the mutant. The
      nucleotide sequence of the mqo gene was determined and is the first sequence
      known for this enzyme. The derived protein sequence is similar to hypothetical
      proteins from Escherichia coli, Klebsiella pneumoniae, and Mycobacterium
      tuberculosis.

PMID- 9660198
TI  - Cloning and characterization of 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo)
      transferase genes (kdtA) from Acinetobacter baumannii and Acinetobacter
      haemolyticus.
AB  - 3-Deoxy-D-manno-oct-2-ulosonic acid (Kdo) transferases (KdtA) are multifunctional
      glycosyltransferases with primary structures of low similarity. Totally
      degenerated primers were deduced from two stretches of identical amino acids
      between known KdtA sequences and used to amplify by PCR a kdtA-specific fragment
      from Acinetobacter baumannii ATCC 15308 DNA which was then applied as a probe for
      the cloning and sequencing of the complete Kdo transferase gene. With conserved
      PCR primers for this structural gene from A. baumannii ATCC 15308, also kdtA
      genes of A. baumannii ATCC 19606 and A. haemolyticus ATCC 17906 were obtained,
      cloned from the chromosome and sequenced. The genes coded for proteins with
      similarities to known Kdo transferases. Within the genus Acinetobacter, the
      identity and similarity of the deduced amino acid sequences were 71% and 84.5%,
      respectively. The kdtA sequences of both A. baumannii strains were identical and
      possessed a TTG start codon, whereas ATG was found in the case of A.
      haemolyticus. The genes from Acinetobacter and kdtA from Escherichia coli K-12
      were expressed in the Gram-positive bacterium Corynebacterium glutamicum. In
      vitro tests confirmed the function of the gene products as Kdo transferases,
      which transferred mainly two Kdo residues to a synthetic lipid A precursor of E.
      coli. Also, no differences between the cloned kdtA genes from A. baumanniii, A.
      haemnolyticus and E. coli were observed when tetraacyl or hexaacyl lipid A were
      tested, since all transferases acted more efficiently on the former. With
      limiting amounts of acceptor, all Kdo transferases were able to transfer a third
      Kdo residue with varying efficiency.

PMID- 9660199
TI  - Analysis of the F-actin binding fragments of vinculin using stopped-flow and
      dynamic light-scattering measurements.
AB  - Using amino acids 884-1066 and 884-1012 expressed from chicken vinculin as fusion
      proteins with schistosomal glutathione S-transferase, we determined the binding
      kinetics of the protein fragments with F-actin. We established by the stopped
      flow method a two-step binding process: an initial rapid reaction followed by a
      slower process. The latter is attributed to F-actin cross-linking and/or
      bundling, which was previously detected by viscometry and electron microscopy
      [Johnson, R. P. & Craig, S. W. (1995) Nature 373, 261-264]. This is also
      supported by dynamic light-scattering measurements, indicating dramatic changes
      in the internal actin filament dynamics, i.e. in bending undulations due to
      thermal noise. The similar size of the binding reaction for both fusion proteins
      with F-actin indicates that the F-actin binding site(s) on vinculin are located
      between residues 884-1012. No binding of pure glutathione S-transferase or its
      fusion protein with vinculin peptide 1012-1066 with F-actin was detected by
      either method.

PMID- 9660200
TI  - Purification of a 58-kDa protein (ER58) from monkey liver microsomes and
      comparison with protein-disulfide isomerase.
AB  - A 58-kDa protein (ER58) was purified from monkey liver to apparent homogeneity.
      It accounts for more than 3% of microsomal proteins and is highly conserved among
      several mammalian species. The amino acid compositions of the N-terminal part and
      that of two internal peptide fragments present strong similarities with the
      sequence ascribed to phospholipase C-alpha. Numerous proteins exhibiting a high
      similarity with this sequence have been isolated by other investigators. Their
      biological function is controversial. Our purified protein is not active as a
      phosphatidylinositol-specific phospholipase C, protease or carnitine acyl
      transferase. Although less efficient than authentic protein-disulfide isomerase,
      ER58 catalyses the glutathione-dependent reduction of insulin and the
      reorganization of disulfide bonds of randomly oxidized (scrambled) ribonuclease
      in reducing conditions. In contrast, ER58 is devoid of oxidizing activity on
      thiol groups of reduced proteins. Many studies suggest that the proteins bearing
      the phospholipase C-alpha sequence could be considered as protein-disulfide
      isomerase isozymes. Our results indicate that ER58 is not totally similar to
      protein-disulfide isomerase in performing thiol :protein-disulfide oxidoreductase
      reactions and suggest that the two proteins may exert distinct cellular
      functions.

PMID- 9660201
TI  - Renal and hepatic nitrogen metabolism during NH4Cl ingestion in protein-deprived
      rats.
AB  - Three groups of rats were given either a standard protein diet, a protein-free
      diet, or a protein-free diet with the inclusion of 0.28 M NH4Cl in their drinking
      water, for 10 days. Body, liver and kidney masses were decreased similarly in the
      protein-free and protein-free NH4Cl groups. Ingestion of protein-free diet
      resulted in profound systemic acidosis in both groups, the simultaneous
      consumption of NH4Cl having no further effect. The activities of the urea-cycle
      enzymes carbamoyl-phosphate synthease, ornithine transcarbamoylase,
      arginosuccinate lyase and arginase were significantly reduced in the protein-free
      group, and the simultaneous ingestion of NH4Cl had no further effect. These
      results indicate that ammonium ingestion does not prevent the decrease in urea
      cycle enzyme activities during a period of dietary-protein deprivation. Renal
      phosphate-dependent glutaminase activity was unchanged in the protein-free group,
      but was significantly higher with simultaneous NH4Cl consumption, suggesting that
      the renal adaptation to acid ingestion is not compromised by a lack of dietary
      protein. Urinary ammonia excretion also increased in rats consuming protein-free
      diet and NH4Cl. Urinary urea excretion was greater in rats receiving protein-free
      diet and NH4Cl than in rats receiving protein-free diet only, at all time-points
      examined. These data demonstrate that urea synthesis is driven primarily by the
      need to dispose of protein-derived ammonia rather than bicarbonate.

PMID- 9660202
TI  - Identification of peptides inhibiting enzyme I of the bacterial
      phosphotransferase system using combinatorial cellulose-bound peptide libraries.
AB  - The phosphoenolpyruvate(P-pyruvate)-dependent sugar phosphotransferase system
      (PTS) is a transport and signal-transduction system which is almost ubiquitous in
      bacteria but does not occur in eucaryotes. It catalyzes the uptake and
      phosphorylation of carbohydrates and is involved in signal transduction, e.g.
      catabolite repression, chemotaxis, and allosteric regulation of metabolic enzymes
      and transporters. EI (Enzyme I of the PTS) is the first and central component of
      the divergent PTS (P-pyruvate-dependent sugar phosphotransferase system)
      phosphorylation cascade. Using immobilized combinatorial peptide libraries and
      phosphorimaging, heptapeptides and octapeptides were identified which selectively
      inhibit EI in vitro. The IC50 of the best peptides is 30 microM which is close to
      the K(M) (6 microM) of EI for its natural substrate HPr (histidine containing
      phosphoryl carrier protein of the PTS). The affinity-selected peptides are better
      inhibitors than a peptide with the active-site sequence of HPr. The selected
      peptides contain several basic residues and one aromatic residue which do not
      occur in the active site of HPr. The large proportion of basic residues most
      likely reflects charge complementarity to the strongly acidic active-site pocket
      of EI. Guanidino groups might facilitate by complexation of the phosphoryl group
      the slow phosphorylation of the peptide.

PMID- 9660203
TI  - Airbags and children: a spectrum of C-spine injuries.
AB  - Over 30 children who were improperly restrained or in rear facing safety seats
      have been reported killed in motor vehicle accidents (MVA) involving airbags. The
      authors report one minor and two major injuries in properly restrained children
      in the front passenger seat. In case 1, A 10-year-old seat-belted boy was
      involved in an MVA (40 km/h) with deployment of both airbags. Physical
      examination findings showed right hyphema with corneal abrasion, right cheek
      abrasion and minimal cervical tenderness. C-spine x-ray was normal. He was
      treated for whiplash and facial burns resulting from contact with hot gas
      released by the airbags and discharged. In case 2, a 4-year-old boy wearing a
      lapbelt was in a MVA (20 km/h) with airbag deployment. On arrival, his Glasgow
      coma score was 3 and he was hemodynamically unstable. Secondary survey after
      stabilization showed left neck abrasions and ecchymoses, quadraplegia, priapism,
      and absent rectal tone. C-spine x-ray showed atlanto-occipital dislocation with
      possible complete spinal cord transection at C1. Aggressive maneuvers were
      withheld, and the patient was pronounced dead. Autopsy findings confirmed the
      clinical diagnosis. In case 3, a 3-year-old boy in a forward-facing safety seat
      was in a MVA (60 km/h) with air bag deployment. The patient was fully awake. C
      spine x-rays were normal. Because of fluctuating level of consciousness, he
      underwent head computed tomography (CT) scan, which demonstrated a posterior
      fossa subarachnoid hemorrhage and a hematoma posterior to the odontoid,
      suggesting a ligamentous tear. He remained asymptomatic and was discharged on day
      6. A head CT scan at 1 month showed a periosteal reaction in the area of the alar
      ligament suggestive of partial ligamentous avulsion; this injury was the
      forerunner of atlanto-occipital dislocation. Airbags deploy by releasing a hot
      effluent at 300 km/h. Mechanisms of injury include direct contact of hot gas with
      facial skin and energy transmitted directly from the airbag system to the child's
      head and neck. These cases illustrate a spectrum of C-spine injuries caused by
      airbag deployment and support the recommendation that children under 12 years of
      age travelling in a car equipped with dual airbags be seated in the back.

PMID- 9660204
TI  - Bolus intravenous infusion of amino acids or lipids does not stimulate
      gallbladder contraction in neonates on total parenteral nutrition.
AB  - BACKGROUND/PURPOSE: Stimulation of gallbladder contraction in patients receiving
      total parenteral nutrition (TPN) may be beneficial in preventing cholestatic
      jaundice associated with TPN. Bolus intravenous administration of either amino
      acids or fat promotes gallbladder contraction in normal adult volunteers after a
      period of starvation. This phenomenon has not been investigated in patients
      receiving continuous TPN. The aim of this study was to test the hypothesis that
      bolus intravenous infusion of amino acids or fat produces gallbladder contraction
      in neonates receiving TPN. METHODS: Twenty-eight studies of gallbladder
      contraction were performed in 18 neonates receiving continuous TPN (median
      weight, 2.3 kg; range, 1.3 to 7.3; gestational age, 37 weeks; range, 28 to 40;
      age, 6.5 days; range, 2 to 180). Different types of experiments were performed:
      (1) bolus intravenous infusion of amino acid or fat for 60 minutes at twice the
      normal infusion rate; (2) bolus intravenous infusion of amino acid or fat for 15
      minutes at four times the normal infusion rate. Gallbladder volume was measured
      by real-time ultrasonography by a single investigator. Measurements were made
      before starting the bolus infusion and every 15 minutes for 1 hour. RESULTS: The
      volume of the gallbladder before bolus intravenous infusion was not significantly
      different between experiments (median, 985; range, 603 to 1,802 mm3). These
      volumes are consistent with an enlarged and atonic gallbladder as previously
      reported in infants receiving parenteral nutrition. In all experiments there was
      no significant decrease in gallbladder volume after bolus infusion of either
      amino acids or fat. CONCLUSIONS: Contrary to their effects in adults, bolus
      infusions of amino acids or fat did not induce gallbladder contraction in
      neonates on TPN. This may have been because of lack of starvation in the neonates
      and/or the effect of continuous glucose infusion.

PMID- 9660205
TI  - Congenital thymic cysts in children--mostly misdiagnosed.
AB  - BACKGROUND/PURPOSE: Thymic cysts are rare lesions of the neck and mediastinum
      that are difficult to diagnose. Often considered inconsequential, these lesions
      can frequently be symptomatic. In this report the authors contrast their
      experience with that of the literature. METHODS: From 1984 through 1997, the
      authors encountered 14 patients with this lesion. All cysts were completely
      excised. Patients that had an acquired cyst of the thymus were excluded from this
      series. RESULTS: Of the 14 patients ranging in age from 2 weeks to 16 years,
      seven patients had cervical masses, five had mediastinal masses, and two children
      had both sites involved. Seven children were symptomatic with wheezing and upper
      respiratory infection, with cough and fever being the most common clinical
      features. Investigations included chest radiograph, contrast esophagram,
      sonography (US) and computerized tomography (CT). Displacement of vital
      mediastinal or neck structures was observed in eight patients. Only two patients
      received correct diagnosis before surgery. Successful and complete excision of
      all cysts was achieved. The cysts were benign and ranged in size from 2 to 22 cm
      in diameter. CONCLUSION: Often forgotten, thymic cysts are rare benign lesions
      that should be considered in the differential diagnosis of cervical and
      mediastinal masses in children.

PMID- 9660206
TI  - Elective partial splenectomy in childhood.
AB  - BACKGROUND & PURPOSE: The indications and results of elective partial splenectomy
      in children remain uncertain. The aim of this study was to determine (1) the
      indications for elective partial splenectomy (EPS), (2) the extent of splenic
      resection, and (3) the complications of EPS. METHODS: Patients who underwent EPS
      from three centers over a 10-year period (1986 through 1996) were studied.
      Variables analyzed included clinical presentation and indications for EPS, extent
      of resection performed, perioperative transfusions, and complications.
      Postoperatively, splenic viability was determined by regular Doppler ultrasound
      scan and splenic function on peripheral blood film analysis. RESULTS: EPS was
      attempted in 12 children for various conditions: giant epithelial cyst (n = 6),
      hypersplenism and metabolic disease (n = 4), pseudotumor (n = 1), and abscess (n
      = 1). One procedure was converted to total splenectomy because of thin splenic
      tissue around an infected giant cyst. No child required transfusion for splenic
      bleeding. There were no postoperative complications or deaths. Only 7 of the 12
      children received prophylactic preoperative immunisation. In the 11 successful
      cases splenic remnant viability remains confirmed by ultrasound scan and normal
      blood film. There has been no significant splenic regrowth or recurrent
      hypersplenism in the four children with metabolic disorders. CONCLUSIONS: EPS is
      suitable for benign splenic conditions and can be performed without major blood
      loss. Preoperative vaccination is advisable. Up to 95% of the spleen can be
      safely removed, basing the blood supply of the residual spleen tissue on
      peripheral polar vessels, with adequate postoperative function.

PMID- 9660207
TI  - Enterocolitis after the surgical treatment of Hirschsprung's disease: risk
      factors and financial impact.
AB  - BACKGROUND/PURPOSE: Enterocolitis (EC) represents a serious complication after
      the surgical correction of Hirschsprung's disease (HD). Although previous studies
      have identified risk factors associated with the development of this complication
      before definitive repair, the factors leading to EC after pull-through have not
      been examined. This study was therefore designed to determine risk factors for
      the development of post-pull-through EC. METHODS: Patients with HD treated from
      1991 through 1996 at the Hospital for Sick Children in Toronto, Canada were
      assessed. Risk factors were examined in three areas: patient factors (gender, age
      at diagnosis, age and weight at pull-through), technical factors (type of repair,
      number of stages, location of transition zone, previous EC), and mechanical
      factors. RESULTS: In 105 consecutive patients, the incidence of postoperative EC
      was 32%. There was no mortality. The risk of postoperative EC was significantly
      increased by mechanical factors related to anastomotic complications (relative
      risk, 2.8) and intestinal obstruction (relative risk, 3.5). This finding was not
      attributable to the general occurrence of any postoperative complication because
      the incidence of postoperative complications was equally distributed in patients
      with and without EC. The presence of EC significantly increased the number of
      hospital admissions, mean length of stay, and total treatment cost. CONCLUSION:
      These findings suggest the use of measures to decrease mechanical obstruction so
      as to decrease the incidence and impact of this potentially devastating
      complication.

PMID- 9660208
TI  - Esophageal function in achalasia: preoperative and postoperative manometric
      studies.
AB  - BACKGROUND/PURPOSE: Aperistalsis observed in children with achalasia may be
      secondary to sphincteric spasm or reflect a primary esophageal dysfunction. The
      aim of this study was to assess manometrically sphincteric function and
      esophageal motility before and after successful myotomy. METHODS: Conventional
      stationary and pull-through manometry were performed preoperatively in 14
      patients and postoperatively in 13. Ambulatory 24-hour manometry was carried out
      in four and eight patients in these two groups, respectively, and the results
      were compared with those of 23 refluxing youngsters. RESULTS: Sphincter hypertony
      with lack or incompleteness of relaxation was found preoperatively in all
      patients, and sphincter pressure decreased dramatically after myotomy in all of
      them. All patients had aperistalsis preoperatively, and only a few had some
      primary, but weak, contractions postoperatively. Ambulatory manometry results
      confirmed a reduced number of motor events even during meals and only
      insignificant improvement of progressiveness, completeness and amplitude of waves
      after myotomy irrespective of the time elapsed since the procedure, the degree of
      recovery of esophageal caliber, and the clinical outcome. CONCLUSIONS: Motor
      disorders in achalasia in children are similar to those of adults with the same
      disease. Motor recovery is observed only in some patients, although it is never
      complete, and their esophagi will remain ineffective for life. Because myotomy
      destroys the sphincter, and motility is permanently impaired in this condition, a
      fundoplication must be interposed to allow long-term mucosal protection.

PMID- 9660209
TI  - Impact of magnetic resonance imaging on the surgical management of cystic
      hygromas.
AB  - BACKGROUND: The surgical management of cystic hygromas can be challenging, and
      accurate diagnosis and anatomic localization is essential. The literature on the
      use of magnetic resonance imaging (MRI) in pediatric cystic hygromas is sparse
      and mostly limited to radiological descriptions. METHODS: The authors present
      five cases of cystic hygromas in children ranging in age from 1 to 13 years. The
      preoperative MRI scans and patient charts were reviewed with attention to the
      clinical, radiological, surgical, and histological findings. RESULTS: MRI
      produced highly detailed multiplanar renderings of the cystic hygromas that were
      both diagnostic and predictive of the subsequent intraoperative findings. This
      modality helped specifically in some cases to identify lesion extensions that
      required specific surgical attention. There were no recurrences or complications
      at a mean follow-up of 18 months. CONCLUSION: The use of MRI in cystic hygromas
      can facilitate accurate diagnosis and assist in the preoperative planning,
      thereby contributing to the successful treatment of these lesions.

PMID- 9660210
TI  - Papillary cystic neoplasm of the pancreas: a report of three pediatric cases and
      literature review.
AB  - BACKGROUND/PURPOSE: Papillary cystic neoplasms are rare pancreatic tumors that
      typically present in women in their third decade of life. Few cases have been
      reported in children. METHODS/RESULTS: The authors report on three pediatric
      patients: a 10-year-old boy, an 11-year-old girl, and a 14-year-old girl. The
      authors have reviewed the existing literature on papillary cystic neoplasms of
      the pancreas and suggest that these tumors probably arise early in life, grow
      slowly, and metastasize infrequently. CONCLUSION: Even when these tumors
      metastasize, patients seldom die as a result of the malignancy.

PMID- 9660211
TI  - Prophylactic thyroidectomy for medullary thyroid carcinoma in gene carriers of
      MEN2 syndrome.
AB  - BACKGROUND/PURPOSE: Although medullary thyroid carcinoma (MTC) can occur
      sporadically, in the pediatric population it is most often associated with the
      multiple endocrine neoplasia syndrome (MEN type 2). Traditional screening was
      based on evaluation of basal and stimulated serum calcitonin levels. The recent
      cloning of the MEN2 gene on the RET proto-oncogene of chromosome 10 now allows
      for testing of gene carrier status in individuals at risk who could benefit from
      prophylactic treatment. The current study was undertaken to determine the
      appropriate age for safe total prophylactic thyroidectomy. METHODS: Over a 16
      year period, 12 patients with a family history of MEN2A and one with a MEN2B
      underwent total thyroidectomy and central neck dissection without parathyroid
      autotransplantation. Four patients (31%) were treated previously for
      Hirschsprung's disease. RESULTS: In seven patients (mean age, 11.8 years)
      undergoing biochemical screening for diagnosis, multifocal MTC and C cell
      hyperplasia (CCH) were found in all the resected specimens. Of six patients
      identified with genetic screening (mean age, 9.1 years), two had elevated
      stimulated calcitonin levels, one (age 14) had evidence of MTC, and one (age 6)
      had CCH. Four patients with normal calcitonin levels had no evidence of MTC (ages
      6, 8, 10) but there was one occurrence of CCH (age 11). No permanent
      postoperative hypoparathyroidism or recurrent laryngeal nerve damage occurred in
      this series. With a mean follow-up of 4 years (range, 1 to 14 years), the overall
      disease-free survival is 100%. CONCLUSIONS: From this study the authors conclude
      that total thyroidectomy can be performed safely in children and should be the
      treatment of choice in patients with a family history of MEN2A carrying a
      germinal RET mutation even if the serum basal or stimulated serum calcitonin
      level is normal. Total thyroidectomy should be performed as early as 5 years of
      age before the occurrence of CCH or MTC.

PMID- 9660212
TI  - Successful treatment of liver hemorrhage in the premature infant.
AB  - Intraoperative neonatal liver hemorrhage usually results in exsanguination and
      death. The parenchyma of a neonatal liver is fragile, and the capsule is very
      thin, unlike that in the pediatric and adult patient. This renders the treatment
      of a neonatal liver fracture almost universally unsuccessful. The current report
      describes two cases of successful management of intraoperative neonatal liver
      hemorrhage during surgery for necrotizing enterocolitis (NEC).

PMID- 9660213
TI  - Undergraduate pediatric surgery objectives: goal and reality.
AB  - BACKGROUND/PURPOSE: Educational objectives can be used both in the
      standardization of curricula and in their evaluation. Surveys of subspecialty
      objectives can clarify educational priorities and identify areas of proficiency
      and deficiency. METHODS: Fifty-one third-year and 56 fourth-year medical students
      were surveyed on their perceived mastery level of 60 pediatric surgery cognitive
      objectives. The same objectives were also used to survey 34 pediatric surgeons
      and 126 practicing family physicians. Physicians' expected and students' self
      reported proficiency was scored for each objective from 0 (not required/unaware
      of condition) to 3 (confident with diagnosis and management of condition).
      Information regarding pediatric surgery instruction was also obtained from the
      undergraduate deans of 12 Canadian medical schools. Data were analyzed using
      descriptive methods and one-way analysis of variance (ANOVA) and were compared
      with existing objectives listings in the subspecialty. RESULTS: Students'
      familiarity scores increased significantly from third-year to fourth-year (P <
      .05), and approximated in fourth year the expected proficiency levels. Family
      physicians' and pediatric surgeons' expectations were remarkably similar. Eleven
      items were identified by both physician groups as nonessential (mean score <
      1.5), whereas 29 were perceived as essential (score > 2.0). The fourth-year
      students' perceived knowledge of all but 3 of these 29 objectives was adequate.
      Comparison of the data with previous objectives listings showed similar expected
      competencies. Deans' data showed varied but mostly limited exposure to pediatric
      surgery in the undergraduate curriculum. CONCLUSIONS: The current study has
      allowed a revision of undergraduate objectives in pediatric surgery based on
      broad stakeholder input. It has also clarified both the expected and the
      perceived student mastery of these objectives, and identified areas of specific
      stress required. The results can be used toward establishing a unified, reliable,
      undergraduate curriculum for pediatric general surgery.

PMID- 9660214
TI  - Alterations in respiratory status: early signs of severe necrotizing
      enterocolitis.
AB  - BACKGROUND: Necrotizing enterocolitis (NEC) presents with well-recognized signs
      of intestinal inflammation such as bilious vomiting, bloody stool, abdominal
      distension, and tenderness. The authors observed otherwise unexplained changes in
      the respiratory status requiring increased respiratory support during the 24
      hours before direct evidence of the intestinal disorder in patients with severe
      NEC. METHODS: To study this observation the authors collected data on 10
      consecutive patients in whom NEC required an operation. RESULTS: Eight of these
      patients were recovering from respiratory distress syndrome (RDS). During the 24
      hours before any direct sign of intestinal dysfunction seven of these eight had a
      respiratory prodrome needing increased respiratory support. Two patients required
      intubation and mechanical ventilation. Five needed increased supplemental oxygen.
      This prodrome included decreased oxygenation in seven, increased respiratory rate
      in five, and increased PCO2 in five, preceded by hypocarbia in three.
      CONCLUSIONS: These changes in the respiratory condition revisit the concept of
      high output respiratory failure. This term was introduced to describe the
      respiratory failure in adult patients who suffer acute intestinal illness.
      Increased metabolic demand from the intestinal illness was thought to stress the
      ability of the patient to delivery oxygen and remove carbon dioxide. The ability
      of the respiratory system to meet the increased demands is limited by the
      intestinal dysfunction itself (abdominal pain and distension). In our patients
      recovering from RDS the pulmonary reserve is inherently limited. Because they are
      carefully monitored, it is easy to retrieve evidence of respiratory changes that
      precede the direct signs of intestinal disease. In the earliest stages of
      intestinal illness before the direct signs of intestinal dysfunction, these
      patients often manifest unexplained signs of respiratory compensation and
      decompensation and require increased respiratory support. Regardless of the
      pathophysiology, these alterations in respiratory status represent an early
      warning sign of NEC.

PMID- 9660215
TI  - Abnormal distribution of intestinal pacemaker (C-KIT-positive) cells in an infant
      with chronic idiopathic intestinal pseudoobstruction.
AB  - BACKGROUND: Chronic idiopathic intestinal pseudoobstruction (CIIPO) is a rare
      syndrome with an obscure pathogenesis. The proto-oncogene c-kit encodes a
      transmembrane tyrosine kinase receptor C-KIT that is critical for the development
      of the interstitial cells of Cajal, cells that are regarded as being the
      pacemaker cells of the gut. Thus, C-KIT immunopositive (C-KIT-) cells in the
      muscle layers of the bowel are considered to be intestinal pacemaker cells.
      METHODS: In this study, the distribution of intestinal pacemaker cells was
      examined for the first time using C-KIT immunohistochemistry in an infant with
      CIIPO. RESULTS: C-KIT+ cells were found lying on either side of the border
      between the two muscle layers (longitudinal and circular) of the bowel and
      dispersed unevenly throughout both muscle layers. Myenteric plexuses were not
      demarcated by C-KIT+ cells. In contrast, in controls, C-KIT+ cells were located
      distinctly between the two muscle layers of the small bowel and dispersed evenly
      throughout the muscle layers of the colon. Myenteric plexuses were clearly
      demarcated by C-KIT+ cells. CONCLUSIONS: This case demonstrates for the first
      time that there is abnormal distribution of intestinal pacemaker cells in CIIPO
      and provides new evidence that abnormal c-kit gene expression may be responsible
      for autonomic gut dysmotility. C-KIT immunohistochemistry may be an indispensable
      tool for diagnosing CIIPO.

PMID- 9660216
TI  - Cougar attacks on children: injury patterns and treatment.
AB  - PURPOSE: Cougar attacks on humans appear to be on the rise. A review of all
      attacks on children was performed to determine the method of attack and injury
      patterns so that a treatment regimen as well as possible preventative measures
      could be determined. METHODS: A review of all attacks, including attacks on
      children, was performed, including three recent attacks treated at our
      institution. Situation, adult supervision, patient age, injuries recorded,
      survival, and mode of attack, if known, were reviewed. RESULTS: There were 50
      documented attacks on children with a 25% fatality rate. Most children were not
      alone at the time of the attack (92%), and in many instances adult supervision
      was present or nearby. Severe head and neck lacerations along with puncture
      wounds were the most common injury. Examples of typical cervical injuries include
      a nonfatal vertebral artery injury, phrenic nerve injury, a fatal internal
      carotid artery injury, and a fatal cervical spine injury. The cougar was rabid in
      two cases. Pasteurella resulted in late infections in two patients. CONCLUSIONS:
      Based on the pattern of injuries, the authors recommend aggressive evaluation for
      occult cervical injuries as well as surgical debridement. Antibiotics should
      cover oropharyngeal flora including Pasteurella multocida. Rabies prophylaxis is
      indicated. Adult supervision in wilderness areas is not necessarily protective.

PMID- 9660217
TI  - Cystic thyroid lesions in children.
AB  - BACKGROUND/PURPOSE: Cystic lesions of the thyroid encompass a wide and
      heterogeneous group of disease states in children, ranging from benign purely
      cystic entities to malignant tumors. The purpose of this study was to study both
      the presentation and management of cystic thyroid lesions in the pediatric
      population. METHODS: A retrospective review of all thyroid masses presenting
      between 1978 and 1996 and found to be purely or partially cystic on ultrasound
      examination was conducted, looking at presentation, family history, laboratory
      values, ultrasound scan and radionuclide imaging, and pathological and
      cytological evaluation. RESULTS: Twenty-four patients (19 girls, 5 boys) aged 6
      to 18 years received the diagnosis of cystic lesions of the thyroid. Of these, 23
      presented with painless neck masses, 21 were clinically euthyroid, only one had a
      single abnormal thyroid function test, only two had mildly positive antithyroid
      antibody test results, and nearly 30% had a positive family history of thyroid
      disease. Ultrasonography showed pure cysts in five patients and mixed solid
      cystic lesions in 19 patients. On scintiscan, six lesions were hot, 13 were cold,
      three showed normal uptake, and two were mixed. Treatment included either
      observation, aspiration, cyst sclerosis, surgery, or combinations thereof.
      Pathological and cytological results included follicular adenoma (n = 9), cystic
      degeneration (n = 6), multinodular goiter (n = 4), carcinoma (n = 2), branchial
      cleft cyst (n = 1), and undetermined (n = 2). CONCLUSIONS: Thyroid cysts are
      often thought to represent benign degenerative disease. Our study, which is the
      first in the literature to specifically address thyroid cysts in children, shows
      that ultrasound scan is useful in evaluating thyroid masses, whereas laboratory
      and radionuclide are of less value, and that single lesions of mixed echogeneity
      are likely to represent neoplasms, a significant percentage of which are
      malignant.

PMID- 9660218
TI  - Inflicted esophageal perforation.
AB  - Esophageal perforation in children is uncommon. A 2 1/2-year-old girl presented
      with multiple soft tissue injuries of various chronological ages. Initial lateral
      cervical spine films showed the presence of a prevertebral air collection with
      soft tissue swelling. Enhanced computerized tomography confirmed the presence of
      proximal esophageal rupture and a retropharyngeal abscess. External drainage of
      the abscess and intravenous antibiotics led to resolution of the perforation in
      13 days. Discrepancies in the history and the constellation of injuries pointed
      to an inflicted etiology (through child abuse). Since 1984, 21 case studies have
      described inflicted esophageal perforation. Common mechanisms of injury include
      foreign body ingestion and blunt or penetrating external trauma. Early diagnosis
      of these injuries reduces both acute and long-term morbidity and mortality.
      Pediatric surgeons must be aware of inflicted injury as an etiology of esophageal
      and hypopharyngeal perforation.

PMID- 9660219
TI  - Laparoscopic evaluation of the pediatric inguinal hernia--a meta-analysis.
AB  - BACKGROUND/PURPOSE: For over 50 years there has been debate over how to manage
      the contralateral groin in children who present with a unilateral inguinal
      hernia. Many preoperative and intraoperative tools to diagnose a contralateral
      patent processus vaginalis or true inguinal hernia have been described. In 1992
      laparoscopy was introduced as a new diagnostic test. Although multiple series
      have assessed this new tool, none of them have been able to statistically show
      that laparoscopy is effective in assessing the contralateral groin. By combining
      all published studies and using the technique of meta-analysis, intraoperative
      laparoscopy can be shown to be effective in diagnosing a contralateral patent
      processus vaginalis in children undergoing unilateral inguinal herniorrhaphy.
      METHODS: All available studies of children with a unilateral hernia who had
      exploration of the contralateral groin by laparoscopy were reanalyzed.
      Sensitivity and specificity of laparoscopy was determined using open exploration
      or development of a metachronous hernia as the gold standard. RESULTS: Nine
      hundred sixty-four patients were suitable for analysis. A contralateral hernia
      was seen on laparoscopy in 376 patients. All of these patients underwent open
      contralateral exploration. A patent processus vaginalis or true hernia sac was
      found in 373. The sensitivity of laparoscopy was 99.4% (95% confidence interval
      97.87 to 99.91). Five hundred eighty-eight patients had a laparoscopy with
      negative results. Sixty-two of these patients then had open contralateral
      exploration. In one case, a patent processus vaginalis was found; the other 61
      patients underwent exploration with negative results. In the remaining 526
      laparoscopy-negative patients, follow-up (1 month to 3 years) was used to see if
      a contralateral hernia developed. A metachronous hernia developed in one of the
      526 patients. The specificity of laparoscopy was 99.5% (95% confidence interval
      98.39 to 99.87). Laparoscopy added an average of 6 minutes to the surgical time
      and was accurate regardless of the technique. There were two minor complications
      related to laparoscopy and no deaths. CONCLUSIONS: Laparoscopy may be the ideal
      tool to diagnose a contralateral patent processus vaginalis intraoperatively. It
      is sensitive, specific, fast, and safe. Although the presence of a patent
      processus does not imply that the patient will go on to develop a metachronous
      hernia, identifying and ligating a patent processus should certainly prevent the
      development of an indirect inguinal hernia.

PMID- 9660220
TI  - Lipid uptake by silicone enteral access feeding devices.
AB  - BACKGROUND/PURPOSE: Deterioration of long-term enteral access devices remains a
      significant patient care and financial problem. Because it is known that lipids,
      particularly medium-chain triglycerides oil (MCT oil), can soften and break
      certain types of polymeric materials, the authors evaluated the effect of liquid
      enteral feeding formulas containing different amounts of MCT oil on silicone
      feeding tubes. METHODS: Commercially available and widely used gastrostomy
      silicone catheters of two sizes (20F and 15F) were sectioned in 5-cm-long samples
      and cleaned. Five groups of five pieces were immersed for 8 weeks in pure MCT oil
      and in four commercial formulas having similar protein, carbohydrate, and fat
      contents. These formulas were chosen because they contained similar percentages
      of fat (37% to 45%), although they contained differing amounts of MCT oil. Sodium
      azide 0.05% was added as a bactericide. Samples were maintained at 37 degrees C
      in an incubator-shaker. After incubation, specimens were rinsed, dried, and
      weighed. Selected samples were extracted with a chloroform-methanol solution
      (2:1). Super-critical fluid chromatography (SFC) and infrared (IR) spectroscopy
      were performed. A tensile tester was used to generate force-elongation curves for
      the remaining samples. A statistical analysis (ANOVA, alpha = .05) was conducted
      to compare data from test groups with results from 20 samples of control silicone
      material. RESULTS: Data demonstrate that silicone is significantly affected by
      liquid formulas and pure MCT oil. SFC and IR findings indicated that fractions of
      MCT oil, corn oil, and canola oil were absorbed by the material. The most
      dramatic weight gain (3.7%) was observed for specimens immersed in pure MCT oil.
      An average increase (9.6%) of silicone compliance was measured along with oil
      migration in the tubing. CONCLUSIONS: Lipid uptake contributes significantly to
      deterioration of the silicone tested, leading to device failure. Surface damage
      can create a potential nidus for microorganisms, particularly fungi. Lipid type
      and rate of administration should be taken into account when long-term enteral
      feedings are given. These data contribute to the understanding of the causes of
      the physico-chemical deterioration of long-term enteral feeding devices and
      provide helpful information for the design and manufacture of improved products.

PMID- 9660221
TI  - Management of gastroschisis with concomitant jejuno-ileal atresia.
AB  - BACKGROUND: The incidence of jejuno-ileal atresia in neonates concomitantly found
      to possess gastroschisis has been reported to be 5% to 25%. Initial treatment for
      this condition has not been well established. METHODS: Thirteen newborns with
      gastroschisis and coexisting jejuno-ileal atresia, were identified and treated at
      our institution over the past 16 years (1978 through 1996). Patient
      characteristics at presentation, surgical therapy, and complications at extended
      follow-up were reviewed. RESULTS: All neonates were preterm (mean gestational
      age, 35.2 +/- 2.0 weeks) and of low birth weight (2.1 +/- 0.4 kg). Atresia types
      II, IIIa, IIIb, and IV were identified at the initial surgical procedure in one,
      eight, one, and three patients respectively; however, one synchronous small bowel
      atresia went unrecognized. A primary anastomosis was fashioned in 8 of 13
      newborns, the creation of which did not influence length of hospitalization,
      length of total parenteral nutrition (TPN) requirement, complication rate, or
      survival; however, reoperation was required in two of eight patients to mediate
      anastomotic complications. Atresia associated with intestinal gangrene or
      perforation was treated by primary anastomosis in three of six patients and the
      remaining three by enterostomy. Primary abdominal wall closure was possible in 10
      of 13 patients; a Silon pouch was required in three. All nine survivors (69%)
      displayed protracted small bowel dysfunction requiring TPN (mean TPN duration of
      3.6 +/- 3.0 months; range, 1 to 11). Mortality in four patients was a consequence
      of severe prematurity, Silon pouch wound sepsis, or TPN-induced cirrhosis.
      CONCLUSIONS: When technically feasible, restoration of intestinal continuity by
      primary anastomosis is a reasonable treatment option in patients with coexisting
      gastroschisis and jejuno-ileal atresia. Favorable outcome is as much a function
      of supportive care and parenteral nutrition as the type of surgical repair
      performed for either the intestinal or the abdominal wall defect.

PMID- 9660222
TI  - Mechanisms underlying intestinal adaptation after massive intestinal resection in
      the rat.
AB  - BACKGROUND/PURPOSE: The regulatory events that control the adaptive response
      after massive intestinal resection are poorly understood. An improved
      understanding could lead to improved clinical therapies. This study tests the
      hypothesis that massive intestinal resection increases nutrient transport by
      upregulation of mRNA for the sodium glucose cotransporter (SGLT1). METHOD: Male
      Lewis rats (225 to 250 g) were studied. Control animals (Con, n = 6) underwent
      ileal transection 15 cm proximal to the cecum; resected animals (Res, n = 8)
      underwent resection of all bowel proximal to the terminal 15 cm of ileum. Animals
      were followed up for 14 days, pair fed, and weighed daily. At the time of death
      the terminal ileum was studied quantifying SGLT1 mRNA using reverse transcriptase
      polymerase chain reaction (RT-PCR) normalized to B-actin, in vitro glucose
      transport in Ussing Chambers, and histology. RESULTS: All animals survived;
      animals that were transected regained preoperative weight by day 10, and
      underwent resection by day 14. Significant adaptation occurred with increases in
      villus height, (control jejunum 934 +/- 79; control ileum, 811 +/- 64 v resected
      ileum, 949 +/- 83 [P < .05]). Nutrient flux (J mucosal --> serosa; Jms) was
      increased in resected ileum (3-0 Methyl-D-Glucose flux: 0.71 +/- 0.2 v 0.56 +/-
      0.04 in Con ileum [P < .05; units, micromol/cm2/hr of 3-0 Methyl-D-Glucose]).
      This was paralleled by an increase in expression of the SGLT1 gene in resected
      ileum, 104 +/- 14, versus Con ileum, 74 +/- 9 (P < .05; values normalized versus
      expression of B-actin). CONCLUSION: SGLT1 expression may be useful as a marker of
      the adaptive process after massive resection and potentially may be used as an
      endpoint of therapy after resection clinically.

PMID- 9660223
TI  - Mucoepidermoid carcinoma of the parotid gland: a rare presentation in a young
      child.
AB  - Although mucoepidermoid carcinoma (MEC) is the most common malignant salivary
      gland neoplasm in childhood and adolescence, it is rarely found in children under
      the age of 10. A 6-year-old girl had an asymptomatic neck mass for 5 months.
      Clinical examination findings showed a 1.5-cm smooth and firm but mobile
      nontender mass located in the upper left anterior cervical triangle, clinically
      separate from the parotid gland. Ultrasound examination findings showed a
      vascular mass, with a cystic component, possibly within the tail of the parotid
      gland. An excisional biopsy was performed and frozen section showed a low-grade
      MEC. A left superficial parotidectomy was then performed. Final histopathologic
      examination showed one positive resection margin. Subsequently, reexcision of the
      surgical site and an upper modified neck dissection was undertaken. This unusual
      presentation of MEC as a neck mass in one of the youngest reported patients
      illustrates that the anatomic region for parotid tumors is large. Possibly some
      of these tumors may arise from heterotopic or accessory parotid tissue.

PMID- 9660224
TI  - Multiple bowel atresias after syngeneic fetal small bowel transplantation in
      rats.
AB  - PURPOSE: The aim of this study was the assessment of atresia formation after
      syngeneic fetal small bowel transplantation (SBTx) to clarify its pathogenesis.
      METHODS: Seventy Lewis rat fetuses (gestational age, 18 to 19 days) were obtained
      by hysterotomy, and a 30-mm long section of small bowel was excised from each
      fetus. Each bowel graft was then transplanted into the space between the
      peritoneum and the rectus abdominis in 70 adult Lewis rats to expose the grafts
      to ischemic stress. Transplantation was successful in 63 of 70 grafts (90%).
      Successfully transplanted bowel grafts were harvested for macroscopic and
      microscopic examination 10 days posttransplantation. RESULTS: Of the successfully
      transplanted grafts, only two (3%) were atresia free; 127 atretic segments were
      found in the remaining 61 grafts. Twenty-four grafts (38%) had a single atresia
      comprised of membranous stenosis (MS) in two, membranous atresia (MA) in 10, and
      blind ends (BEs) with or without a connecting tissue remnant in 12. Thirty-seven
      grafts (59%) had multiple atresias, comprised of MS, MA, or both in six, BEs
      alone in seven, and a combination of BEs with MS or MA in 24. CONCLUSIONS: Our
      model is the first to succeed in inducing experimentally membranous stenosis and
      a high incidence (59%) of multiple atresias. These results suggest that bowel
      ischemia is responsible for multiple bowel atresia formation.

PMID- 9660226
TI  - Reduced glial cell line-derived neurotrophic factor level in aganglionic bowel in
      Hirschsprung's disease.
AB  - BACKGROUND/PURPOSE: Glial cell line-derived neurotrophic factor (GDNF) is
      suggested to be essential for the development of the enteric nervous system. The
      aim of this study was to investigate GDNF protein expression in human aganglionic
      (AG) bowel in Hirschsprung's disease (HD) using immunofluorescence and enzyme
      linked immunosorbent assay (ELISA) analysis, to further understand the
      pathophysiology of HD. METHODS: Colonic specimens were obtained from eight
      patients with HD (aged 7 days to 14 months) at the time of definite pull-through
      surgery, including both normoganglionic (NG) and aganglionic (AG) segments.
      Immunofluorescence was performed using anti-GDNF polyclonal antibody and FITC
      conjugated secondary antibody on the formalin-fixed and paraffin-embedded
      specimens. For ELISA analysis, specimens were homogenized by adding 10 volumes of
      10-mmol/L phosphate-buffered saline containing proteinase inhibitors. Centrifuged
      supernatant was used for the quantitative analysis using sandwich-type ELISA for
      human GDNF. RESULTS: There was strong GDNF immunoreactivity in the mucosal
      epithelium, submucosal and myenteric plexuses, and hypertrophic nerve trunks. In
      the mucosa in AG bowel, the number of GDNF immunoreactive epithelial cells was
      significantly reduced compared with NG bowel (mean +/- SD, AG/NG = 227.2 +/-
      73.1/310.8 +/- 80.5 GDNF immunoreactive cells per 100 crypts, P < .05). Using
      ELISA, the level of GDNF in full-thickness bowel was reduced significantly in AG
      bowel compared with NG bowel (mean +/- SD, AG/NG = 860.2 +/- 309.8/1777.5 +/-
      271.4 pg/g wet tissue, P < .001). CONCLUSION: Because GDNF is essential for the
      development of the enteric nervous system, our findings of reduced level of GDNF
      in AG bowel as well as reduced number of GDNF immunoreactive cells in the mucosa
      of AG bowel suggest that GDNF may play an important role in the pathogenesis of
      HD.

PMID- 9660225
TI  - The natural history of sacrococcygeal teratomas diagnosed through routine
      obstetric sonogram: a single institution experience.
AB  - BACKGROUND/PURPOSE: The antenatal diagnosis of sacrococcygeal teratoma (SCT) is
      increasingly being made with fetal sonography. However, the natural history of
      SCT detected on routine obstetric sonogram is not well defined. METHODS: A
      retrospective chart review of 21 fetal SCT diagnosed on routine sonography at
      Hospital Sainte-Justine between 1980 and 1997 were performed. The patients'
      clinical and sonographic characteristics, prenatal, and perinatal outcomes were
      examined. Prognostic criteria were identified by correlating patients'
      characteristics with outcome. RESULTS: In utero mortality rate was 19% and
      perinatal mortality rate was 14%. The incidence of premature labor was 50%. Of
      the various criteria examined as an independent variable, the presence of a solid
      tumor was found to be a important negative prognostic factor with a 67% incidence
      of death in utero and an overall mortality rate of 100%. Patients with new onset
      polyhydramnios were at significant risks for premature labor (100%). All of the
      perinatal deaths were attributable to tumor rupture. CONCLUSIONS: The course of
      sacrococcygeal teratoma diagnosed on routine sonograms is associated with a
      higher-than-expected incidence of prenatal and perinatal complications. Close
      antenatal follow-up for new onset polyhydramnios and the presence of a completely
      solid tumor will help optimize patient counseling and treatment.

PMID- 9660227
TI  - Results of transplantation for acute and chronic hepatic allograft rejection.
AB  - BACKGROUND/PURPOSE: Transplantation for rejection is a requirement in liver
      transplant recipients when allograft failure is imminent. The authors evaluated
      the outcome of these children and their allografts. METHODS: The medical records
      of 129 children who received a liver transplant were reviewed retrospectively.
      Twelve children required transplantation for biopsy-proven rejection--10 chronic
      and two acute. Overall patient and graft survival were compared with children
      receiving primary liver transplants. The current allograft function of the
      patients undergoing transplants was also reviewed. Statistical significance was
      determined by Fisher's Exact test. RESULTS: Twelve children received at least one
      retransplant for biopsy-proven rejection. Graft survival at 1 year was 58% (v 79%
      for primary transplants) and patient survival was 83% (vs 89%). Two allografts
      were lost because of primary allograft nonfunction. Three additional allografts
      were lost-two to recurrent rejection and one to hepatic artery thrombosis. Two
      patients who lost a second transplant to rejection required a total of seven
      transplants to treat rejection. Two children died, one of primary nonfunction and
      one of adenovirus pneumonia. The 10 surviving patients all have excellent graft
      function (total bilirubin, 0.74 +/- 0.38, aspartate aminotransferase, 40 +/- 22).
      CONCLUSION: These data suggest that transplantation for rejection can be
      accomplished safely with a patient survival rate comparable to primary liver
      transplantation; however, graft loss is excessive and underscores the need for
      more adequate immunosuppression.

PMID- 9660228
TI  - Sensitivity and cost minimization analysis of radiology versus olive palpation
      for the diagnosis of hypertrophic pyloric stenosis.
AB  - BACKGROUND/PURPOSE: Two strategies are commonly used for the initial diagnosis of
      hypertrophic pyloric stenosis (HPS): (1) physical examination and (2) radiologic
      evaluation using upper gastrointestinal series (UGI) or sonography. The authors
      wished to determine the sensitivity and relative cost of each strategy. METHODS:
      The charts of 234 patients presenting over 3 years with a history suggestive of
      HPS were reviewed retrospectively. Cost, expressed as mean diagnostic charges
      (MDC) and mean total charges (MTC), was calculated according to two theoretical
      models. In model A, all patients first are examined by a surgeon. If an olive is
      palpable, they proceed to surgery. If not, they are sent to radiology. In model
      B, all patients have radiologic investigation first, and then surgical evaluation
      if the study result is positive. RESULTS: Of the 234 patients, 150 had HPS (64%).
      Olives were appreciated in 111 of these (palpation sensitivity of 74%). There was
      one false-positive olive (0.7%) and no false-negatives. Sonography and UGI were
      equally accurate (sensitivity of 100%, 0.5% false-positive). Equations were
      generated to estimate MDC and MTC for our patient population under each model. In
      model A, MDC = $507 - ($221 x palpation sensitivity) and MTC = $2,543 ($240 x
      palpation sensitivity). In model B, MDC = $449 and MTC = $2,454, and costs were
      independent of ability to feel an olive. When cost was plotted against palpation
      sensitivity, model A yielded a lower MDC than model B if palpation sensitivity
      was at least 26%, and a lower MTC if palpation sensitivity was at least 37%.
      Because our palpation sensitivity was 74%, approximately $100 per patient would
      be saved by sending all infants suspected of having HPS to a surgeon for
      examination as an initial step. CONCLUSIONS: Although highly sensitive, imaging
      is superfluous if an olive is palpable. Children suspected of having HPS should
      have a surgical consultation before a radiology study as long as the surgeon's
      palpation sensitivity for an olive is at least 37%. Improved palpation skills
      will result in maximum financial savings.

PMID- 9660229
TI  - Single-port tracheoscopic surgery in the fetal lamb.
AB  - BACKGROUND/PURPOSE: Endoscopic fetal surgery could help avoid many of the
      problems associated with open fetal surgery, but the use of multiple ports may be
      too traumatic to the membranes. The authors describe a single-port technique of
      tracheoscopic surgery in the fetus. METHODS: Time-dated pregnant ewes (95 to 105
      days; term, 145 days) underwent midline laparotomy under general halothane
      anesthesia. A 5-mm-diameter balloon-tipped cannula was introduced in the uterus
      by Seldinger technique. A 1.2-mm semirigid mini-endoscope, fitted inside a 9F, 20
      degrees curved sheath, was introduced under continuous, low-pressure irrigation,
      inside the fetus' mouth, and advanced into the trachea. RESULTS: Endotracheal
      procedures, including temporary (n = 11) and permanent balloon tracheal occlusion
      (n = 30) and placement of a barbed guide wire for endotracheal occlusion device
      insertion (n = 12), were performed by introducing a 1-mm diameter instrument
      alongside the telescope. These were successfully performed in 52 of the 53
      fetuses. The rigidity of the telescope allowed controlled access to the pharynx;
      its curve allowed full tracheobronchial endoscopy with the fetus in utero.
      CONCLUSIONS: The present technique marries the control and optical quality of a
      rigid endoscope with the physiological curve only a flexible instrument could
      offer until now. The types of procedures performed with this technique illustrate
      its potential as a research tool; the size (1.2-mm diameter), shape, and optical
      qualities of the telescope should make clinical applications possible.

PMID- 9660230
TI  - Contractile properties of intralobar pulmonary arteries and veins in the fetal
      lamb model of congenital diaphragmatic hernia.
AB  - BACKGROUND/PURPOSE: Pulmonary hypertension plays a significant role in the
      pathophysiology of congenital diaphragmatic hernia (CDH). Although there has been
      an intensive research effort directed at mediators that may cause pulmonary
      vasoconstriction, no single agent has been identified. The authors hypothesize
      that there may be an alteration in the cGMP-nitric oxide (NO) pathway of
      vasodilatation contributing to the pulmonary hypertension observed in CDH. The
      purpose of these studies is to begin to elucidate vasoactive properties of
      pulmonary vessels with particular attention to the cGMP-NO pathway of
      vasodilatation in fetal lambs with CDH. METHODS: Fourth-generation pulmonary
      arteries and pulmonary veins were dissected from both right and left lungs of
      eight, 139-day gestational fetuses with surgically created CDH. Vessels were
      studied with standard isolated tissue bath techniques. Experiments examined basal
      release of NO in endothelium-intact PVs and PAs of both right and left lungs by
      measuring the contractile force of vessels constricted with norepinephrine (NE)
      in the presence and absence of the nitric oxide synthase (NOS) inhibitor N(omega)
      nitro-L-arginine (L-NA). Concentration-response curves to the vasodilating agents
      zaprinast and A23187 were also obtained in vessels contracted by NE. RESULTS:
      Left and right pulmonary artery responses to NE are enhanced over those of
      historic controls. Pretreatment of left pulmonary arteries with L-NA enhances the
      vasoconstrictor response to NE, whereas right PAs show no increased response.
      Relaxation responses to A23187 and zaprinast, in both left and right pulmonary
      arteries were not different from control lambs. Relaxation responses of both left
      and right pulmonary veins to A23187 and zaprinast are blunted compared with
      controls. This blunting is significantly more in left pulmonary veins than right.
      Further, right but not left pulmonary veins display enhanced vasoconstrictive
      response to NE after L-NA pretreatment. CONCLUSIONS: The NO-cGMP pathway of
      vasodilatation is abnormal in the near term, fetal lamb with CDH. These
      abnormalities were most apparent in pulmonary veins and may reflect abnormal NOS
      activity or content between left and right lungs of the fetal lamb with CDH.
      Pulmonary arteries from CDH lambs have basal and stimulated NO release equal to
      that of historic controls but appear to be hypersensitive to exogenous
      vasoconstrictors.

PMID- 9660231
TI  - Cervical ECMO cannula placement in infants and children: recommendations for
      assessment of adequate positioning and function.
AB  - BACKGROUND/PURPOSE: Cervical extracorporeal membrane oxygenation (ECMO) cannula
      position is often difficult to confirm by chest x-ray alone. Malposition requires
      a second surgery to rectify the problem. Reoperation places the patient at risk
      for infection, bleeding, or death. This study analyzes indications for cannula
      repositioning and suggests an alternative standard for intraoperative evaluation
      of catheter function as it relates to position. METHODS: The authors reviewed
      charts of 73 patients placed on arterio-venous ECMO through cervical vascular
      access. Reasons for repositioning of either cannula at the initial surgery or
      postoperatively were recorded. RESULTS: Of 73 patients, 18 (24.6%) required
      either arterial cannula or venous cannula repositioning. In 10 (55%) of these
      patients, cannula malposition was not detected by chest x-ray during the initial
      cannulation, and they therefore required a second cervical exploration for
      repositioning. CONCLUSIONS: Chest x-ray is not sensitive in demonstrating
      malpositioned cervical ECMO cannulae. Two-dimensional ECHO before wound closure,
      may be a superior, more cost effective means of assessing cannula placement and
      function than x-ray alone. Confirmation of cannula position and function, before
      wound closure, would reduce the risks involved with cervical reexploration.

PMID- 9660232
TI  - Allogeneic fetal intestinal transplantation with FK506 immunosuppression.
AB  - PURPOSE: Small intestinal transplantation remains a significant clinical problem.
      Allogeneic fetal intestinal (AFI) transplantation shows promise, particularly
      regarding procurement; however, no studiesto date have evaluated the potential
      success of true allogeneic loci implantation. The authors hypothesized that
      isolated segments of AFI could be heterotopically transplanted but would require
      immunosuppression to survive. METHODS: Donor tissue was obtained from late
      gestation Brown Norway rat fetuses with a histo-locus RTN and Fischer fetuses
      with a histo-locus RT1L. The recipients were adolescent male Fischer rats with a
      histo-locus RT1L. A 1.2-cm segment of fetal small bowel was implanted in the
      omentum of the recipient rat and allowed to mature for 5 weeks. Animals were then
      separated into five groups. Group A served as controls with syngeneic fetal
      intestinal (SFI) transplant. Group B received AFI with no immunosuppression;
      group C, AFI transplant with five days of FK506; group D, AFI with 10 days of
      FK506; and Group E, AFI with daily FK506 for the entire 5-week maturation period.
      Animals were killed on day 35. RESULTS: All animals gained weight over the
      maturation period. Groups B, C, and D had no viable transplant segments at day
      35. Groups A and E both had well-developed viable segments confirmed by gross and
      histological evaluation. CONCLUSIONS: FK506 allows for normal intestinal
      development for use in allogeneic fetal bowel transplantation. With this
      observation, the use of fetal intestine transplanted into the portal circulation
      emerges as a potentially viable alternative to present intestinal transplant
      models.

PMID- 9660233
TI  - Association of extrarenal Wilms' tumor with a horseshoe kidney.
AB  - Nephroblastoma (Wilms' tumor) is the most common renal malignancy in childhood.
      Extrarenal Wilms' tumor is uncommon, and the diagnosis is almost always
      postsurgical. The authors report two cases, located in the sigmoid mesocolon, one
      of these having an associated horseshoe kidney. Both were treated with excision
      followed by chemotherapy. They are now 36 months and 7 months postchemotherapy,
      respectively, and are symptom and recurrence free. Both had favorable
      histological findings. Association with a horseshoe kidney raises an important
      issue regarding the histogenesis of these tumors. The authors believe that there
      is a nexus between the fusion of metanephric blastema during the sixth to seventh
      week of intrauterine life and the "ectopic" metanephric blastema cells that may
      give rise to extrarenal Wilms' tumor. Association with a horseshoe kidney with an
      extrarenal Wilms' tumor has been reported on five previous occasions. The authors
      closely examine the link between the two.

PMID- 9660234
TI  - Liver transplantation as treatment for arterioportal fistulae.
AB  - The authors present the case of a 14-year-old boy with secondary portal
      hypertension caused by arterio-portal fistulae. Ascites, edema, severe abdominal
      pain, and steatorrhea developed in the patient. In an attempt to decrease
      arterioportal flow the authors carried out vascular embolization that was
      partially successful. A liver transplant was performed as a last therapeutic
      resource in view of the fact that it constitutes an accepted therapy for patients
      with severe liver disease. Orthotopic liver transplantation may be considered as
      another possible treatment of arterio-portal fistulae.

PMID- 9660235
TI  - Ileo-colic intussusception with an unusual retrograde colo-colic intussusception.
AB  - An interesting case with both antegrade and retrograde intussusception in an
      infant is reported. There was no apparent predisposing cause.

PMID- 9660236
TI  - Congenital diaphragmatic hernia associated with aortic coarctation.
AB  - Congenital diaphragmatic hernia (CDH) may be associated with other anomalies,
      most frequently cardiovascular in nature. Despite fetal echocardiography,
      diagnosis of an accompanying cardiac malformation often is not made until after
      birth and sometimes not until after extracorporeal membrane oxygenation (ECMO)
      has been instituted. Aortic coarctation associated with CDH may occur as an
      isolated, surgically correctable malformation or it may be a component of the
      usually fatal left heart "hypoplasia" or "smallness" syndrome. The authors
      present two cases of aortic coarctation associated with CDH requiring ECMO that
      illustrate the management challenges of these coincident diagnosis. In one case,
      the accompanying coarctation was suspected and required precannulation
      angiography for confirmation, whereas in the other case, the diagnosis of
      coarctation was not made until after ECMO cannulation. Depending on its anatomic
      location and severity, an aortic coarctation associated with life-threatening CDH
      may limit the physiological efficacy of venoarterial ECMO. Furthermore, arterial
      cannulation for extracorporeal support requires that flow through the remaining
      carotid artery be maintained during aortic reconstruction, which may prove
      difficult for lesions best treated by subclavian flap angioplasty. When the
      diagnosis of coincident aortic coarctation and CDH is suspected or proven before
      institution of extracorporeal support, serious consideration should be given to
      venovenous bypass, because this may provide better postductal oxygenation and
      facilitate aortic repair with the option of left carotid artery inflow occlusion.

PMID- 9660237
TI  - Omphalopagus parasite: a rare congenital anomaly.
AB  - Omphalopagus parasite is a very rare congenital anomaly. Presented here is a case
      in which an extra truncus was attached to an infant in the region of the
      epigastrium. The truncus had well-formed extremities, an abdomen, and a
      hypoplastic thorax. The infant had a small omphalocoele in addition to the
      truncus. Surgery performed in the neonatal period helped to achieve a successful
      separation of the truncus from the host.

PMID- 9660238
TI  - Bowel motility in infants and children born with duodenal atresia and stenosis.

PMID- 9660239
TI  - Treatment of Hirschsprung's disease.

PMID- 9660240
TI  - Treatment of Hirschsprung's disease.

PMID- 9660241
TI  - A second-generation enzyme immunoassay for detection of antibodies to IFN-alpha.
AB  - We have developed a solid-phase enzyme-linked immunoassay (EIA) for detecting
      antibodies to interferon-alpha2 (IFN-alpha2) in serum or plasma. In this assay,
      based on the sandwich principle, the capture antigen, IFN-alpha2, is covalently
      bound to the wells in 96-well plates. This novel procedure offers considerable
      advantages over the antigen binding by passive adsorption used in most previous
      EIA. Specific antibodies present in clinical specimens bind to the anchored
      antigen and are detected by adding peroxidase-labeled IFN-alpha2 and a peroxidase
      substrate mixture. The resultant color is a function of the concentration of
      antibody in the sample. The assay has proved to be convenient, precise, and
      reproducible and can detect as little as 1-5 ng/ml of specific antibody IgG.

PMID- 9660242
TI  - Localization of a molecular form of interferon-regulated RNase L in the
      cytoskeleton.
AB  - RNase L (also termed 2-5A-dependent RNase) is a crucial enzyme involved in the
      molecular mechanism of interferon (IFN) action. Activated by 2',5'-oligoadenylate
      oligomers (2-5A), this enzyme controls the regulation of RNA stability in IFN
      treated or virus-infected mammalian cells. Knowledge of RNase location within
      cells may provide additional information about its function. Previous work
      located RNase as a detergent-soluble molecule in nuclei and cytoplasm. In this
      study, we demonstrate that this enzyme was also present in a detergent-insoluble
      fraction associated with proteins of the cytoskeleton. A cellular fractionation
      procedure was used to prepare the cytoskeleton, which was shown to contain 2-5A
      binding activity not due to cytoplasmic contaminants. In contrast to the
      cytoplasmic fraction, which contained RNase L with a 2-5A-accessible site, the
      insoluble RNase molecular form of the cytoskeleton could not be assayed by the
      classic radiobinding method or the covalent UV cross-linking procedure, which
      only detects the 2-5A binding site in an open position, that is, free of 2-5A or
      with an unmasked 2-5A site. The 2-5A binding site present in the cytoskeleton was
      completely masked and not directly accessible to its 2-5A activator. This
      particular molecular form of RNase can be detected after a specific denaturing
      renaturing treatment of the cytoskeleton, which separates the RNase from
      cytoskeletal proteins, unmasking the 2-5A site. The cytoskeletal RNase was no
      longer present at this site when cells were stimulated for a short time with 12-O
      tetradecanoylphorbol-13-acetate (TPA). Our data suggest the existence of a
      pathway that targets the RNase to another subcellular location. To explore the
      issue further, we examined in vitro the ability of calcium and phospholipid
      dependent protein kinase C (PKC) to catalyze significant phosphorylation of the
      RNase.

PMID- 9660243
TI  - Oral food challenge increases in vitro IL-4 production by peripheral blood
      mononuclear cells in allergic patients.
AB  - The aim of this study was to investigate interferon-gamma (IFN-gamma) and
      interleukin-4 (IL-4) production by peripheral blood mononuclear cells (PBMC) in
      response to oral challenge in patients with food allergy. Thirty-one patients
      were compared with 10 healthy subjects. Cell cultures were prepared before and
      150 min after single-blind, placebo-controlled, oral food challenge. In vitro
      production of cytokines was observed after stimulation with phytohemagglutinin
      (PHA) plus phorbol myristate acetate (PMA). Patients were characterized according
      to their reactions. In vitro IL-4 production was significantly greater in
      patients with food sensitization than in controls. The 18 patients with positive
      food challenge presented significantly greater IL-4 production after food
      challenge than before. IFN-gamma production was not modified. In the 10 control
      subjects and in 13 patients with negative food challenge, IL-4 and IFN-gamma
      production was comparable before and after food challenge. The increased IL-4
      production in patients with positive oral food challenge could account for the
      development of polysensitization. This situation might be relevant to other
      allergic diseases and to treatments.

PMID- 9660244
TI  - Interferon-containing controlled-release polymers for localized cerebral
      immunotherapy.
AB  - Controlled-release ethylene-vinyl acetate copolymers (EVAc), which were used
      previously for the in vivo intracerebral delivery of chemotherapeutics, were
      evaluated as a possible route of localized intracerebral delivery of interferon
      (IFN). Natural mouse IFN-alpha/beta (Mu-IFN-alpha/beta) was incorporated into
      polymers at 5% or 10% by weight with 2 x 10(4) U or 4 x 10(4) U, respectively. In
      vitro and in vivo studies of the release of Mu-IFN-alpha/beta from EVAc polymers
      showed the released IFN to be biologically active, as determined by the
      inhibition assay of viral cytopathic effect (CPE). Evaluation of the in vitro
      kinetics of release showed that most of the IFN activity was released in the
      first 4 days, with the rest being released thereafter. The in vivo kinetic
      release of Mu-IFN-alpha/beta from intracerebrally implanted polymers showed that
      most of the IFN activity was released within 24 h after polymer implantation in
      the hemisphere ipsilateral to the polymer. This IFN activity gradually decreased
      over the next 72 h, with a significant linear trend (p < 0.0001). The hemisphere
      contralateral to the implanted polymer showed no significant levels of IFN
      activity throughout the 4 days of evaluation. By contrast, blood levels of IFN
      increased from day 1 to day 4, showing a significant linear trend (p = 0.0125),
      with IFN levels on day 4 being significantly higher (p < 0.05) than on day 1
      after polymer implant. This study demonstrates the feasibility of intracranial
      controlled local delivery of IFN using a polymer delivery device.

PMID- 9660245
TI  - Deprivation of leukemia inhibitory factor by its function-blocking antibodies
      augments T cell activation.
AB  - Leukemia inhibitory factor (LIF) is a cytokine that acts on a wide range of cell
      types in vitro, but knowledge of its physiological role is limited. High levels
      of LIF protein have been selectively detected in the thymus throughout postnatal
      development. LIF-deficient mice have shown impaired thymic T cell maturation,
      suggesting the possibility that T cells require LIF for maturation. We have used
      highly specific antibodies raised against native rat LIF to inhibit LIF function
      during a defined and restricted period of thymic T cell maturation (first
      postnatal week). Surprisingly, we observed increased T cell activation in the LIF
      deprived wild-type rat. The increased T cell response is retained even 4 weeks
      after anti-LIF treatment when the level of LIF in the thymic microenvironment has
      returned to normal. Our results are in contrast to findings with LIF knockout
      mice, where decreased T cell activation was observed. These observations suggest
      that LIF may have alternative effects on various phases of T cell development and
      that LIF may be involved in the restriction of the T cell repertoire during
      maturation occurring in the first postnatal week.

PMID- 9660247
TI  - Variations in the interferon-inducing capacity of Sendai virus subpopulations.
AB  - Several Sendai virus (SV) preparations, propagated through eggs from the same
      viral seed, exhibited significantly different capacities to induce interferon
      (IFN) in human leukocytes (nHu-IFN-alpha). The amount of induced IFN and the
      numbers of SV IFN-inducing particles (IFP) per cell were determined in dose (SV
      concentration)-response (IFN yield) curves, kinetics of IFN production, and
      coinfection experiments with SV preparations that differed in IFN-inducing
      capacities. The possible role of leukocyte sources and the quality of the SV
      preparations and of allantoic fluids in affecting the IFN-inducing capacity of SV
      populations also were tested. The data indicate that different SV preparations
      induced different amounts of IFN per leukocyte and contained approximately the
      same concentrations of IFN-inducing particles. There was no apparent correlation
      between the IFN induced and the apparent quality of the SV preparations examined
      (EID50, HAU, and EID50/HAU). The leukocyte source and the allantoic impurities of
      SV preparations did not have any influence on the magnitude of the IFN yield.
      Similar shapes of the dose-response curves, the absence of any lag in the
      kinetics of IFN production, and the ability of a viral preparation that induced
      low yields of IFN to suppress partially a high-yielding inducer suggest that a
      common mechanism of induction is always present. Hence, propagation of SV in eggs
      from low multiplicity produced virus stocks that differed significantly in their
      inducing capacity, suggesting that genetic bottlenecks may be operative.

PMID- 9660246
TI  - Effects of IFN-beta on human cerebral blood flow distribution.
AB  - The effect of interferon-beta1b (IFN-beta) on human cerebral blood flow
      distribution was examined in five multiple sclerosis patients using functional
      brain single-photon emission tomography (SPECT). Of nine regions of interest
      studied, only the basal ganglia exhibited a significant change (increase) in
      relative photon emission intensity (i.e., relative blood flow) when comparing
      SPECT scans obtained 6 h after s.c. IFN-beta injection with scans obtained at the
      same time of day (noon) 30 h after IFN-beta injection (IFN-beta-free day). The
      increase in relative blood flow to the basal ganglia following IFN-beta injection
      correlated positively with changes in mean arterial pressure (MAP). Additional
      studies will be required to determine the relevance of these observations for IFN
      beta-induced central nervous system side effects.

PMID- 9660248
TI  - Chicken interferon types I and II enhance synergistically the antiviral state and
      nitric oxide secretion.
AB  - This report shows that chicken type I and type II interferons (IFNs), like their
      mammalian counterparts, act synergistically such that a mixture of the two has
      much greater activity than that expected from the separate contribution of each
      type. The degree of antiviral synergy was measured by virus plaque reduction and
      cytopathic effect (CPE) inhibition in both primary and secondary chicken embryo
      cell cultures. Mixtures of the two Ch-IFNs produced antiviral effects 3-10 times
      greater than that expected from strict additivity of each IFN acting alone. At
      high concentrations of IFN mixtures there was a qualitative shift to an
      exponential IFN action does-response curve that revealed synergistic effects
      greater than 100-fold. Synergy resulted even with mixtures containing less than 1
      U/ml of either type of Ch-IFN. The antiviral effects developed more rapidly with
      mixtures than when type I or II Ch-IFN was used alone. Mixtures of the two types
      of Ch-IFN synergistically potentiated nitric oxide secretion in cells of the HD11
      chicken macrophage line. Molecular mechanisms are cited that may account for
      synergy between type I and type II IFNs, and speculation is offered on the
      epidemiologic and therapeutic implications of synergy in vivo.

PMID- 9660249
TI  - The development of autoimmune encephalomyelitis provoked by myelin
      oligodendrocyte glycoprotein is associated with an upregulation of both
      proinflammatory and immunoregulatory cytokines in the central nervous system.
AB  - Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the
      central nervous system (CNS). We previously reported upregulation of gene
      expression for a number of proinflammatory cytokines, interleukin-1beta (IL
      1beta), IL-2, IL-6, tumor necrosis factor-alpha (TNF-alpha), TNF-beta, and
      interferon-gamma (IFN-gamma), in the CNS of mice with myelin basic protein (MBP)
      induced relapsing EAE by using semiquantitative reverse transcriptase-polymerase
      chain reaction (RT-PCR). However, in these mice there was no significant increase
      of gene expression for immunoregulatory cytokines (IL-4, IL-10, transforming
      growth factor-beta [TGF-beta]). We report here that gene expression for both
      proinflammatory and immunoregulatory cytokines increased during the course of
      disease in the CNS of mice with myelin oligodendrocyte glycoprotein (MOG)-induced
      nonrelapsing EAE. These results indicate that the gene expression pattern of
      immunoregulatory cytokines in the CNS may be different between MBP-induced and
      MOG-induced EAE and that it may influence the type of disease. Accordingly, the
      course of the disease may be influenced by the interplay between the
      proinflammatory and immunoregulatory cytokines.

PMID- 9660250
TI  - Serotonin derivative, N-(p-coumaroyl) serotonin, inhibits the production of TNF
      alpha, IL-1alpha, IL-1beta, and IL-6 by endotoxin-stimulated human blood
      monocytes.
AB  - We have reported that N-(p-coumaroyl) serotonin (CS) and its derivatives with
      antioxidative activity are present in safflower seeds. As reactive oxygen species
      (ROS) are implicated in the signaling of lipopolysaccharide (LPS), we examined
      whether CS has a suppressive effect on inflammatory cytokine generation from
      human monocytes in vitro. CS at 50-200 microM reduced tumor necrosis factor
      (TNF), interleukin-1 (IL-1), and IL-6 activities in the culture supernatants from
      LPS-stimulated human blood monocytes without cytotoxicity. ELISA assay revealed
      that the production of TNF-alpha, IL-1alpha, IL-1beta, and IL-6 was inhibited by
      CS. Northern blot analysis showed that LPS-induced expression of these cytokine
      mRNA in monocytes was suppressed by CS. NF-kappaB activation was also inhibited
      by CS. These findings indicate that CS has a suppressive effect on
      proinflammatory cytokine production from monocytes, and this effect is based in
      part on the suppression of cytokine mRNA expression through inhibition of NF
      kappaB activation.

PMID- 9660251
TI  - Signal transduction in LPS-activated aged and young monocytes.
AB  - Aged monocytes, that is, monocytes purified from the blood of donors > or =65
      years of age, when compared with young monocytes, that is, monocytes purified
      from the blood of young donors 25 years of age, display a decrease in interleukin
      6 (IL-6) and tumor necrosis factor (TNF) production after activation by
      lipopolysaccharide (LPS). The LPS concentration required to obtain IL-6 and TNF
      production is much higher for aged monocytes than for young monocytes.
      Furthermore, the intensity of TNF and IL-6 production was much weaker for LPS
      activated aged monocytes than for LPS-activated young monocytes. In addition,
      deficient protein kinase C (PKC)-alpha, PKC-/betaI, and PKC-betaII activation,
      deficient mitogen-activated protein kinase (MAP-Kinase) activation, and deficient
      expression of c-Fos and c-Jun was observed in LPS-activated aged monocytes when
      compared with LPS-activated young monocytes. These data suggest that age induces
      human monocyte immune deficiencies that could be observed not only at the
      functional level but also in the signal transduction pathways.

PMID- 9660252
TI  - Does an analysis of exhaled air indicate the metabolic state of critically ill
      patients?

PMID- 9660253
TI  - Opioids and the cardiovascular responses to haemorrhage and injury.

PMID- 9660254
TI  - Application of a new method for analysis of exhaled gas in critically ill
      patients.
AB  - OBJECTIVE: Application of a new method for analysis of exhaled gas in critically
      ill patients. DESIGN: Open study. SETTING: Surgical intensive care unit of an
      university hospital. PATIENTS: Thirty-seven consecutive, critically ill,
      mechanically ventilated patients. INTERVENTIONS: None. MEASUREMENTS AND RESULTS:
      Chemical analysis of the patient's exhaled gas was based upon substance
      adsorption and concentration onto activated charcoal, microwave desorption and
      gas chromatographic separation. Patients with acute respiratory distress syndrome
      (ARDS) exhaled less isoprene than those without ARDS [9.8 (8.2-21.6) vs 21.8
      (13.9-41.4) nmol/m2 per min [median (95% confidence interval)], p = 0.04]. In
      patients who developed pulmonary infection, pentane elimination increased from
      0.4 (0.0-5.4) to 2.7 (0.6-6.1, p = 0.05) nmol/m2 per min and isoprene elimination
      decreased from 5.2 (0-33) to 5.0 (0-17, p = 0.05) nmol/m2 per min, resulting in a
      significant increase in pentane/isoprene ratio from 0.1 (0-0.3) to 0.4 (0-15, p =
      0.007) when compared to patients without pulmonary infection. CONCLUSIONS: The
      new method allows quantitative analysis of human gas samples with low substance
      concentrations and is well suited for clinical studies which involve the
      investigation of metabolic processes in the lung and the body.

PMID- 9660255
TI  - Oxygen tolerance in patients with acute respiratory failure.
AB  - OBJECTIVE: To search for a threshold of pulmonary oxygen toxicity in patients
      with acute respiratory failure. DESIGN: Retrospective study over a 10-year
      period. SETTING: Three intensive care units of two university hospitals. PATIENTS
      AND PARTICIPANTS: Seventy-four patients with acute respiratory failure ventilated
      continuously with a FIO2 > or = 0.9 for at least 48 h were selected.
      INTERVENTIONS: Information regarding status, scoring, diagnosis and therapeutic
      interventions upon admission and ICU course were extracted from the patients'
      charts. MEASUREMENTS AND RESULTS: We found that total exposure [mean (standard
      error of the mean)] to a FIO2 of 0.9 (TE 90) or more was 5.6 (1.1) days in the 17
      survivors (S) versus 5.9 (0.5) days in the 57 non-survivors (D) (NS). Total
      exposure time to a FIO2 more than 0.5 (TE 50) was 16.5 (2.6) days in S and 11.2
      (1) days in D (p < 0.05). The PaO2/FIO2 ratio became significantly higher in S
      only 5 days after beginning FIO2 of 0.9 or more. Hypoxemia was not frequent at
      the time of death, whereas in 70% of the non-survivors there were at least three
      organ failures in the last 48 h. In univariate analysis, the duration of exposure
      to FIO2 of 0.9 or more was not different in survivors and non-survivors, and the
      average total duration of exposure to FIO2 of more than 0.5 was even longer in
      survivors. In multivariate analysis, exposure shorter than 10 days to FIO2 more
      than 0.5 and exposure longer than 4 days to a FIO2 of 0.9 or more were
      significantly associated with death. However, despite a larger exposure to a FIO2
      of 0.9 or more during the last 5 years of the study, the trend moved towards a
      higher survival rate during this period compared with the first 5 years of the
      study. CONCLUSIONS: Thus, our data provide circumstantial evidence that the lungs
      of patients with acute respiratory failure might exhibit some relative resistance
      to prolonged oxygen exposure. Therefore, it might be worthwhile carrying out a
      prospective study of different FIO2 strategies in such patients.

PMID- 9660257
TI  - Elevation of serum human hepatocyte growth factor (HGF) level in patients with
      pneumonectomy during a perioperative period.
AB  - OBJECTIVE: Proliferation of alveolar type II cells is thought to be critical for
      the restoration of lung function after diffuse alveolar damage or pneumonectomy.
      However, the factors that regulate alveolar type II cell proliferation, and the
      mechanism that brings about compensatory lung growth are not well understood.
      Hepatocyte growth factor (HGF) has been shown to have hepatotrophic and
      nephrotrophic functions for regeneration of the liver and kidney. We have
      attempted to investigate the involvement of HGF in lung regeneration after lung
      resection. DESIGN: A prospective, controlled study. SETTING: Adult surgical
      patients in a university hospital. PATIENTS AND MEASUREMENTS: We measured serum
      HGF levels in eight patients undergoing major lung resection, and in five
      patients undergoing mastectomy as controls, by using radioimmunoassay and an
      enzyme-linked immunosorbent assay. RESULTS: In all cases of pneumonectomy, the
      serum HGF levels increased 3- to 5-fold at 1-3 days (with a peak at 3 days) after
      operation, and then decreased to nearly basal levels in 2 weeks. However, these
      levels in patients undergoing mastectomy did not change much over the first 2
      weeks, postoperatively. CONCLUSIONS: Serum HGF levels increased in patients after
      major lung resection, which suggests that HGF might play an important role in
      lung regeneration or compensatory lung growth in humans.

PMID- 9660256
TI  - Transesophageal echocardiography for the diagnosis of pulmonary embolism with
      acute cor pulmonale: a comparison with radiological procedures.
AB  - OBJECTIVE: The goal of the study was to assess prospectively the value of
      transesophageal echocardiography (TEE) for the diagnosis of massive pulmonary
      embolism complicated by acute cor pulmonale. DESIGN: A prospective study
      conducted on 44 consecutive patients. SETTING: A general intensive care unit
      (ICU) of a university hospital. PATIENTS AND METHODS: Between May 95 and October
      96, 44 consecutive patients with clinically suspected acute pulmonary embolism
      underwent transthoracic echocardiography (TTE), completed by TEE when acute cor
      pulmonale was present (30 patients). The results of the echocardiographic studies
      were compared with radiological investigations by helical CT or contrast
      angiography. RESULTS: The high sensitivity and specificity of the presence of
      acute cor pulmonale on TTE for the diagnosis of pulmonary embolism was confirmed.
      Nineteen patients only underwent TEE. The sensitivity and the specificity of TEE
      in detecting a proximal pulmonary embolism were 84% and 84%, respectively. Its
      main limitation concerned the left pulmonary artery, in which only one thrombus
      was visualized by TEE whereas six were present on helical CT, and lobar pulmonary
      arteries which could not be visualized with TEE. Thus, the overall sensitivity of
      TEE for the detection of pulmonary embolism with acute cor pulmonale was only
      58%. CONCLUSION: In comparison with radiological procedures, TEE had limited
      accuracy for detecting pulmonary embolism with acute cor pulmonale. When the
      pulmonary embolism was located in the main or right pulmonary artery, TEE could
      clarify the diagnosis within a few minutes without further invasive diagnostic
      procedures. However, a negative TEE did not exclude left proximal or lobar
      pulmonary embolism.

PMID- 9660258
TI  - Prognostic importance of gram-negative intestinal colonization preceding
      pancreatic infection in severe acute pancreatitis. Results of a controlled
      clinical trial of selective decontamination.
AB  - OBJECTIVES: To establish, firstly, whether gram-negative (re)-colonization of the
      gut leads to an increased risk of gram-negative pancreatic infections and whether
      this event is time-related and, secondly, whether the difference in the quantity
      and quality of micro-organisms colonizing the digestive tract influences
      morbidity and mortality. DESIGN: Prospective analysis of the results of
      systematic semi-quantitative cultures of several body areas taken from patients
      with severe acute pancreatitis, during a controlled multicenter trial of adjuvant
      selective decontamination. SETTING: Surgical intensive care units of 16
      hospitals. PATIENTS: A total of 2,159 semi-quantitative cultures from the
      oropharynx, rectum and pancreatic tissues taken from 90 patients were analyzed.
      INTERVENTIONS: Surveillance cultures from the oropharynx and rectum were taken on
      admission and repeated twice weekly and from the (peri)-pancreatic devitalized
      tissues (i. e. necrosis) at every relaparotomy and from drainage. MEASUREMENTS
      AND RESULTS: All gram-negative pancreatic infections were preceded by intestinal
      colonization with the same micro-organisms. The risk of developing a pancreatic
      infection following gram-negative intestinal colonization (15/42 patients) was
      significantly higher as compared to patients without gram-negative colonization
      (0/10 patients) (p < 0.001) or to patients in whom E. coli was the only
      intestinal micro-organism cultured (0/30 patients) (p < 0.001). The occurrence of
      intestinal E. coli did not increase the risk of pancreatic infection. Gram
      negative colonization of the rectum and oropharynx significantly correlated with
      the later development of pancreatic infection: relative risks 73.7 (p < 0.001)
      and 13.6 (p < 0.001), respectively. However, when both areas were evaluated
      simultaneously, the rectum was more significant (p < 0.001). The severity of
      intestinal intestinal colonization until the moment of pancreatic infection
      showed an increase in time in all 15 patients. In 11 of 15 patients (73%) these
      infections occurred within 1 week following the first isolation from the
      digestive tract. Gram-negative intestinal colonization was associated with a 3.7
      fold increased mortality risk (p = 0.004). CONCLUSIONS: Gram-negative intestinal
      colonization, E. coli excepted, is an early prognostic parameter in patients in
      whom pancreatic infection has not yet occurred and represents a significantly
      increased risk of pancreatic infections and mortality.

PMID- 9660259
TI  - A standardized neurosurgical neurointensive therapy directed toward vasogenic
      edema after severe traumatic brain injury: clinical results.
AB  - OBJECTIVE: Analysis of a standardized therapy focusing on prevention and
      treatment of vasogenic edema in patients suffering severe traumatic brain injury
      (TBI). DESIGN: A retrospective analysis. SETTING: Neurointensive care unit at
      Sahlgrenska University Hospital, Goteborg, Sweden. PATIENTS: 38 patients with
      severe TBI were included. The median Glasgow Coma Score was 5 (range 3-8) and
      median age 27 years (range 5-70 years). INTERVENTIONS: Measurement of
      intracranial pressure (ICP). Surgical evacuation of hematomas and contusions.
      Volume expansion aiming at normovolemia. Sedation with continuous intravenous
      infusion of low-dose thiopentone and reduction of stress response by clonidine.
      Normalization of capillary hydrostatic pressure by metoprolol and clonidine. If
      ICP and cerebral perfusion pressure (CPP) were not stabilized (ICP < 20 mmHg and
      CPP > 60 mm Hg), a continuous infusion of dihydroergotamine was added. In 4
      patients a craniectomy was performed. RESULTS: Of the 38 patients, 27 (71%)
      survived with good recovery or moderate disability, 5 (13%) survived with severe
      disability, 1 (3%) remained in a vegetative state, and 5 (13%) died. The
      mortality due to intracranial hypertension was 11% (4 patients). CONCLUSION: A
      therapy focusing on treatment of the assumed vasogenic edema in combination with
      aggressive neurosurgery resulted in an outcome as good as the best previously
      reported.

PMID- 9660260
TI  - Role of replacement fluids in the immediate complications of plasma exchange.
      French Registry Cooperative Group.
AB  - OBJECTIVE: Comparison of side effects (fever shivering and/or allergic reactions,
      collapse, symptomatic hypocalcaemia) of the different substitution fluids used
      during therapeutical plasmapheresis. DESIGN: Multicentric retrospective
      comparative study designed to explore the side effects due to the replacements
      fluids (albumin alone or associated with dextran 40, modified fluid gelatin,
      hydroxyethyl starch), and to determine the best combination in patients
      undergoing plasmapheresis. PATIENTS: 46,895 procedures were performed on 5,167
      patients between 1990 and 1994. The analysis concerns 33,962 sessions, divided
      into two groups (group 1: 21,079 sessions from 1990 to 1992 comparing albumin
      alone versus combined albumin-macromolecules and the different combinations among
      these, group 2: 12,883 sessions in 1993-1994 comparing albumin alone versus
      albumin-hydroxyethyl starch). Because of the diversity of the products used,
      13,029 sessions were not studied because groups of small sample sizes were
      formed. MEASUREMENTS AND RESULTS: In group 1, the comparison of albumin +
      macromolecules with albumin alone, shows the best haemodynamic tolerance, lower
      frequency of fever shivering and/or allergic reactions in the albumin alone
      subgroup. On the other hand, hypocalcaemia is significantly higher in this
      subgroup. The combinations albumin + dextran 40 (but after hapten inhibition) and
      albumin + hydroxyethyl starch are equivalent. Albumin + modified fluid gelatin is
      the combination presenting the highest incidence in terms of allergic
      manifestations. In group 2, albumin + hydroxyethyl starch versus albumin alone,
      the former is preferable in terms of the three side effects studied. CONCLUSION:
      The results of this study show a combination of albumin 4% hydroxyethyl starch to
      replace plasma during plasma exchange to be the method presenting the lowest
      morbidity and the best cost/effectiveness ratio.

PMID- 9660261
TI  - Standard calculation of ethanol elimination rate is not sufficient to provide
      ethanol substitution therapy in the postoperative course of alcohol-dependent
      patients.
AB  - OBJECTIVE: Alcohol withdrawal syndrome (AWS) is a severe complication during
      postoperative treatment of alcohol-dependent patients. Besides the use of
      clomethiazole, clonidine, and benzodiazepines, there is another possible way to
      prevent AWS by deliberate administration of ethanol. The appropriate dosage of
      ethanol has not been known up to now and it could be defined according to the
      average ethanol elimination rate (EER) which, from forensic analysis, is known to
      be 15 mg/dl per h in a normal population. However, it is questionable whether
      these data are suitable for the calculation of the correct dosage in alcohol
      dependent patients. DESIGN: Preliminary retrospective descriptive study. SETTING:
      Intensive care unit of a university teaching hospital. PATIENTS: 11 alcohol
      dependent patients (9 males, 2 females, mean age 50.8 years, range 33 to 60
      years). INTERVENTIONS: Ethanol substitution (ES) by parenteral application.
      MEASUREMENTS AND RESULTS: Ethanol kinetics were evaluated by repeated measurement
      of the blood ethanol concentration (BEC) over a period of at least 6 h parallel
      to the administration of ethanol. The average EER was found to be 28 mg/dl per h
      with a standard deviation of 11 mg/ dl per h. The minimum value was 18 mg/dl per
      h and the maximum 50 mg/dl per h. These EERs were significantly higher than the
      EERs known from forensic analysis. AWS was prevented in all 11 patients.
      CONCLUSIONS: Close control of BEC and precise adjustment of ethanol
      administration are necessary prerequisites for ES. The standard EER is not
      sufficient to define the appropriate ethanol dosage due to enormous variations in
      the ethanol metabolism of alcohol-dependent patients.

PMID- 9660262
TI  - Comparison of measured and predicted energy expenditure in mechanically
      ventilated children.
AB  - OBJECTIVE: To determine the energy requirements in mechanically ventilated
      pediatric patients using indirect calorimetry and to compare the results with the
      predicted metabolic rate. DESIGN: In 50 mechanically ventilated children with a
      moderate severity of illness, energy expenditure was measured by indirect
      calorimetry. Daily caloric intake was recorded for all patients. Total urinary
      nitrogen excretion was determined in 31 patients. RESULTS: Although there was a
      close correlation between the measured total energy expenditure (mTEE) and the
      predicted basal metabolic rate (pBMR) (r = 0.93, p < 0.001), Bland-Altman
      analysis showed lack of agreement between individual mTEE and pBMR values. The
      ratio of caloric intake/mTEE was significantly higher in the patients with a
      positive nitrogen balance (1.4 +/- 0.07) compared with those with a negative
      nitrogen balance (0.8 +/- 0.1; p < 0.001). CONCLUSIONS: Standard prediction
      equations are not appropriate to calculate the energy needs of critically ill,
      mechanically ventilated children. Individual measurements of energy expenditure
      and respiratory quotient by means of indirect calorimetry in combination with
      nitrogen balance are necessary for matching adequate nutritional support.

PMID- 9660263
TI  - Assessment of functional residual capacity using nitrogen washout and
      plethysmographic techniques in infants with and without bronchopulmonary
      dysplasia.
AB  - OBJECTIVE: In normal infants, functional residual capacity using plethysmography
      (FRCpleth) exceeds FRC(N2) (using nitrogen washout) and the within-subject
      difference FRC(pleth-N2) indicates the part of pulmonary gas volume not
      ventilated during tidal breathing. We postulated that infants with
      bronchopulmonary dysplasia (BPD) have an elevated FRC(pleth-N2). DESIGN: In a
      prospective study, FRC(pleth-N2) in healthy newborns (controls n = 17) was
      compared to that in neonates recovering from the respiratory distress syndrome
      without BPD (noBPD, studied at discharge, n = 13) and with BPD (BPD1 n = 14,
      studied at 36 post-conceptional weeks; BPD2 n = 16, at discharge). MEASUREMENTS
      AND RESULTS: Paired measurements, FRCpleth and FRC(N2), were performed using a
      plethysmograph (Jaeger, Germany) and an open-circuit nitrogen washout technique
      (SensorMedics 2600, USA). In comparison to the controls (5.2 ml/kg), FRC(pleth
      N2)/kg in noBPD (12.7 ml/kg, p < 0.001), in BPD1 (24.9 ml/kg, p < 0.001) and in
      BPD2 (13.5 ml/kg, p < 0.001) was significantly higher. Compared with that of the
      controls FRCpleth was significantly increased in BPD1 (p < 0.001) and FRC(N2) was
      decreased in noBPD and both BPD groups. CONCLUSION: The FRC(pleth-N2) is a
      reliable indicator for pulmonary inhomogeneities in infants with respiratory
      diseases.

PMID- 9660264
TI  - A scoring system to predict the evolution of respiratory distress syndrome into
      chronic lung disease in preterm infants.
AB  - OBJECTIVE: The purpose of this study was to develop and validate an empirical
      scoring system to predict the evolution of neonatal respiratory distress syndrome
      (RDS) into chronic lung disease (CLD) in preterm infants, by comparing it with a
      more complicated logistic regression model. DESIGN: Clinical study. SETTING:
      Neonatal intensive care unit. PATIENTS: The retrospective analysis of a 3-year
      experience showed that a gestational age (GA) of less than 30 weeks, a birth
      weight (BW) of less than 1000 g, the diagnosis of hyaline membrane disease (HMD)
      and pulmonary interstitial emphysema (PIE) during the first 72 h of life, the
      peak inspiratory pressure (PIP) and the fraction of inspired oxygen (FIO2) were
      the highest relative risk factors correlated with the evolution of CLD. On this
      basis an empirical and a statistical scoring system were defined and
      prospectively applied at 3 and 5 days of life to 228 neonates with BW less than
      1,250 g. The results obtained with both scoring systems were then compared.
      RESULTS: Of the 149 infants surviving at 28 days of life, 67 (GA: 29.9 +/- 2.3
      weeks; BW: 1,058 +/- 143 g) were normal and 82 (GA: 27.5 +/- 3.9 weeks: BW: 838
      +/- 200 g) had CLD. Using a cut-off value of 4.0, the empirical scoring system
      showed a specificity of 97.0% and a sensitivity of 92.7% on the 3rd day of life;
      on the 5th day of life the specificity was still 95.5%, while sensitivity
      remained 92.7%. The areas under the ROC curves plotted with both scoring systems
      tested were similar. CONCLUSIONS: The proposed empirical scoring system is easy
      to use and is highly reliable. The application of this scoring system provides
      the opportunity to direct aggressive treatment for CLD toward only very high risk
      patients between the 3rd and 5th days of life.

PMID- 9660265
TI  - Interleukin-6 levels in serum and lung lavage fluid of children undergoing open
      heart surgery correlate with postoperative morbidity.
AB  - OBJECTIVE: To evaluate the relationship of perioperative levels of interleukin 6
      (IL-6) in serum and bronchoalveolar fluid with morbidity and mortality in
      children undergoing cardiopulmonary bypass (CPB). DESIGN: Prospective,
      noninterventional study. SETTING: Operating room and pediatric intensive care
      unit (PICU) of a university hospital. INTERVENTIONS: None. MEASUREMENTS AND
      RESULTS: IL-6 levels were measured in serum and lung lavage fluid obtained
      before, during, and after CPB using the B9.9 bioassay. Alveolar epithelial lining
      fluid (AELF) volume was calculated using the urea correction method. Mean
      intraoperative AELF IL-6 levels increased fourfold compared to preoperative
      levels, and mean serum IL-6 levels increased fivefold after CPB. Mean
      intraoperative AELF IL-6 levels correlated with intraoperative blood transfusion
      (r2 = 0.18; p = 0.049) and duration of inotropic support (r2 = 0.29; p = 0.009),
      mechanical ventilation (r2 = 0.24; p = 0.019), and PICU stay (r2 = 0.29; p =
      0.008). Mean serum IL-6 levels 2 h after CPB correlated with intraoperative blood
      transfusion (r2 = 0.3;p = 0.007), and with Pediatric Risk of Mortality score on
      postoperative day 3 (r2 = 0.24; p = 0.022), and were higher in patients with
      massive fluid retention (p = 0.014) and in nonsurvivors (p = 0.003). CONCLUSIONS:
      Serum and alveolar IL-6 levels increase after CPB, and correlate with
      postoperative morbidity. Serum IL-6 levels also correlate with mortality. They
      may be useful in assessing the severity of the systemic inflammatory response
      after CPB.

PMID- 9660266
TI  - Determination of functional residual capacity (FRC) by multibreath nitrogen
      washout in a lung model and in mechanically ventilated patients. Accuracy depends
      on continuous dynamic compensation for changes of gas sampling delay time.
AB  - OBJECTIVE: Validation of an open-circuit multibreath nitrogen washout technique
      (MBNW) for measurement of functional residual capacity (FRC). The accuracy of FRC
      measurement with and without continuous viscosity correction of mass spectrometer
      delay time (TD) relative to gas flow signal and the influence of baseline FIO2
      was investigated. DESIGN: Laboratory study and measurements in mechanically
      ventilated patients. SETTING: Experimental laboratory and anesthesiological
      intensive care unit of a university hospital. PATIENTS: 16 postoperative patients
      with normal pulmonary function (NORM), 8 patients with acute lung injury (ALI)
      and 6 patients with chronic obstructive pulmonary disease (COPD) were included.
      INTERVENTIONS: Change of FIO2 from baseline to 1.0. MEASUREMENTS AND MAIN
      RESULTS: FRC was determined by MBNW using continuous viscosity correction of
      TD(TDdyn), a constant TD based on the viscosity of a calibration gas mixture
      (TD0) and a constant TD referring to the mean viscosity between onset and end of
      MBNW (TDmean). Using TDdyn, the mean deviation between 15 measurements of three
      different lung model FRCs (FRCmeasured) and absolute volumes (FRCmodel) was 0.2%.
      For baseline FIO2 ranging from 0.21 to 0.8, the mean deviation between
      FRCmeasured and FRCmodel was -0.8%. However, depending on baseline FIO2, the
      calculation of FRC using TDmean and TD0 increased the mean deviation between
      FRCmeasured and FRCmodel to 2-4% and 8-12%, respectively. In patients (n = 30)
      the average repeatability coefficient was 6.0%. FRC determinations with TDmean
      and TD0 were 0.8-13.3% and 4.2-23.9% (median 2.7% and 8.7%) smaller than those
      calculated with TDdyn. CONCLUSION: A dynamic viscosity correction of TD improves
      the accuracy of FRC determinations by MBNW considerably, when gas concentrations
      are measured in a sidestream. If dynamic TD correction cannot be performed, the
      use of constant TDmean might be suitable. However, in patient measurements this
      can cause an FRC underestimation of up to 13%.

PMID- 9660267
TI  - Bronchoalveolar lavage with a diluted surfactant suspension prior to surfactant
      instillation improves the effectiveness of surfactant therapy in experimental
      acute respiratory distress syndrome (ARDS).
AB  - OBJECTIVE: To assess whether bronchoalveolar lavage (BAL) with a diluted
      surfactant suspension prior to surfactant instillation prevents the only
      transient improvement in lung function as reported after surfactant instillation
      in severe acute respiratory distress syndrome (ARDS). DESIGN: Randomized,
      prospective, experimental study. SETTING: Laboratory and animal facility of a
      large university. MATERIALS: Adult male Sprague-Dawley rats (280 +/- 30 g).
      INTERVENTIONS: All animals underwent repetitive whole lung saline lavage to
      induce acute lung injury. Then, animals were randomly divided into seven study
      groups: the first group received surfactant (150 mg/ kg) within 10 min after the
      last lavage (early treatment), whereas in the other six groups mechanical
      ventilation was continued for 3 h before treatment (late treatment). Treatment
      consisted of: surfactant instillation at a dose of 150 mg/kg; at a dose of 250
      mg/kg; BAL with saline; BAL with a diluted surfactant suspension (2.5 mg/ml); BAL
      with saline, immediately followed by surfactant instillation (150 mg/kg) and BAL
      with a diluted surfactant suspension (2.5 mg/kg), immediately followed by
      surfactant instillation (150 mg/kg). MEASUREMENTS AND RESULTS: Blood gases were
      measured for 6 h and then BAL was performed to measure the protein concentration
      and surface tension properties. Mean PaO2 values increased immediately after
      surfactant instillation to pre-lavage values but remained stable only in the
      group that received surfactant immediately after the lavage procedure and the
      group that underwent BAL with a diluted surfactant suspension prior to surfactant
      instillation. CONCLUSION: BAL with a diluted surfactant suspension prior to
      surfactant instillation at a later time point in lung injury resulted in a stable
      improvement of lung function. This improvement is comparable with the results
      seen after surfactant instillation immediately after lung lavage.

PMID- 9660268
TI  - Perfluorocarbon broncho-alveolar lavage and liquid ventilation versus saline
      broncho-alveolar lavage in adult guinea pig experimental model of meconium
      inhalation.
AB  - OBJECTIVE: This study compares perfluorocarbon broncho-alveolar lavage (PFC-BAL)
      with isotonic saline broncho-alveolar lavage (saline-BAL) in an experimental
      model of meconium aspiration in adult guinea pigs. DESIGN: Prospective controlled
      experimental study. PATIENTS AND METHODS: Ten male guinea pigs were given 1 ml of
      human meconium, diluted to 10% in isotonic saline, via tracheostomy and then
      artificially ventilated. After stabilization, five animals (control group)
      underwent BAL with 10 ml/ kg isotonic saline solution. After bronchial
      suctioning, a further BAL with 2 ml/kg saline was performed. The other five
      animals (study group) underwent BAL with 100 ml/kg of PFC (RIMAR 101).
      Bronchosuction was effected at 5 min and then a BAL with PFC 2 ml/kg was
      performed. Both groups received conventional mechanical ventilation during the
      lavage procedures. Within 20 min all the saline-BAL treated animals died, whereas
      the PFC-BAL treated animals survived and were then treated with total liquid
      ventilation (TLV) by gravity. MEASUREMENTS AND RESULTS: After meconium inhalation
      in both groups, a large alveolar-arterial oxygen difference, hypercarbia, severe
      acidosis and tachycardia were noticed. In PFC treated animals, an improvement in
      blood gases was noted and acid-base balance remained stable compared to saline
      BAL treated animals. No haemodynamic change was observed during or after PFC-BAL,
      while during saline-BAL there was evidence of bradycardia, hypotension and
      respiratory failure, which led to the death of the animals. The histological lung
      sections in the PFC-BAL group showed evidence of normal alveolar expansion with a
      minimal presence of meconium debris in the small bronchioles. In saline-BAL
      treated animals, the lung structure appeared severely compromised with the
      presence of meconium in bronchioles and alveoli, intra-alveolar oedema and
      haemorrhagic areas. CONCLUSIONS: This study confirms the detrimental effects of
      meconium aspiration and the impairment of lung function following saline-BAL. By
      contrast, PFC-BAL and TLV by gravity seemed to prevent absorption of meconium,
      facilitate its removal, improve gas exchange and reduce lung barotrauma.

PMID- 9660269
TI  - Effects of fenoldopam on systemic and splanchnic haemodynamics and oxygen
      delivery/consumption relationship during hyperdynamic ovine endotoxaemia.
AB  - OBJECTIVE: To evaluate the use of a selective dopamine-1 agonist (fenoldopam) to
      provide selective splanchnic vasodilatation during sustained hypotensive
      endotoxaemia in sheep. DESIGN: Randomised, controlled, experimental study.
      SETTING: Animal research laboratory. SUBJECTS: 12 adult instrumented, midazolam
      sedated sheep. INTERVENTIONS: The animals were randomised to receive a 20-min
      continuous infusion of dopamine (10 microg x kg(-1) x min(-1), fenoldopam (10
      microg x kg(-1) x min(-1) and noradrenaline (1 microg x kg(-1) x min(-1)) under
      control conditions and 12 h after endotoxaemia was induced by a continuous
      infusion of Escherichia coli endotoxin producing a stable hyperdynamic state
      simulating human septic shock. This drug dosage was selected to produce a 25-30%
      increase in cardiac output by all three drugs during control conditions.
      MEASUREMENTS AND RESULTS: Systemic and splanchnic haemodynamic data were
      continuously obtained and systemic and splanchnic oxygen delivery (DO2) and
      consumption (VO2) were calculated. Hyperdynamic hypotensive endotoxaemia did not
      modify the splanchnic and renal reduction in DO2 and the vasoconstrictive
      reactivity to noradrenaline observed during control conditions. In contrast,
      endotoxaemia abolished the fenoldopam and dopamine-induced increase in splanchnic
      DO2 (especially in the coeliac trunk) observed during control conditions.
      CONCLUSIONS: During sustained hyperdynamic endotoxaemia, the dopaminergic-induced
      selective increase in coeliac trunk blood flow is abolished, most probably
      because of an already maximally vasodilated splanchnic circulation which
      prevented dopamine or fenoldopam to vasodilate this area further. Contrary to
      common belief, selective dopamine-1 agonist administration under these conditions
      may therefore not be beneficial to the splanchnic organs, though it improves
      whole body DO2 and VO2.

PMID- 9660270
TI  - Modulation of rat brain synaptosomal plasma membrane achieved by atracurium and
      its metabolite laudanosine.
AB  - OBJECTIVE: Atracurium besylate and laudanosine cause excitement and seizures when
      introduced into the central nervous system of laboratory animals. We examined the
      modulation of lipid-protein interaction in the lipid environment of rat brain
      synaptosomal plasma membrane (SPM)-bound enzymes as a possible mechanism leading
      to these effects. METHODS: The effect of various concentrations of atracurium
      besylate and laudanosine, or of varying duration of SPM, on the activity of
      Na+/K+-stimulated ATPase, Mg2+-stimulated ATPase and 5'-nucleotidase were
      assessed. The modulation of lipid protein interaction by laudanosine was
      estimated on the basis of the temperature dependence and cooperative behaviour of
      Na+/K+-stimulated ATPase. RESULTS: The effect of atracurium besylate or
      laudanosine on Na+/K+-stimulated ATPase activity was biphasic. Maximal enzyme
      stimulation appeared at 10(-4) M atracurium besylate or 10(-8) M laudanosine, and
      at 30 min of pre-incubation with both drugs. Arrhenius plots of Na+/K+-stimulated
      ATPase showed a transition temperature of 23.0 +/- 1.2 degrees C in control SPM
      and shifted to 16.5 +/- 0.9 degrees C (p < 0.01) in SPM treated with 10(-8) M
      laudanosine. The Hill coefficients for the allosteric inhibition of Na+/K+
      stimulated ATPase by fluoride decreased from 1.99 +/- 0.22 in controls to 1.06 +/
      0.11 (p < 0.001) in the presence of 10(-8) M laudanosine. CONCLUSIONS: Our
      results suggest that laudanosine, one of the principal metabolites of atracurium
      besylate, affects nerve cell function in rats through the perturbation of the
      membrane lipid structure accompanied by SPM-bound enzyme dysfunction.

PMID- 9660271
TI  - Intraventricular streptokinase infusion in acute post-haemorrhagic hydrocephalus.
AB  - Neonatal post-haemorrhagic hydrocephalus is a clinical condition with a high
      mortality and long-term morbidity. Its clinical management is difficult and not
      well standardized. We describe the case of a term baby suffering from acute
      intracranial hypertension caused by an intraventricular and thalamic haemorrhage.
      In this case, the external ventricular drain inserted to control intracranial
      pressure was ineffective because of repeated obstructions due to blood clots.
      Continuous intraventricular infusion of streptokinase of 20,000 U/day allowed
      quick lysis of the clots, drainage of the cerebrospinal fluid and relief from the
      coma. Although it did not prevent a permanent ventriculoperitoneal shunt, we
      obtained reabsorption of the intraventricular haemorrhage without rebleeding
      complications. We suggest the use of low-dose fibrinolytic infusion through an
      external drain for the treatment of acute intracranial hypertension following
      intraventricular haemorrhage in term infants.

PMID- 9660272
TI  - Timing of recovery of lung function after severe hypoxemic respiratory failure in
      children.
AB  - OBJECTIVE: To describe the timing of recovery of lung function after severe acute
      hypoxemic respiratory failure (AHRF) in children. DESIGN: A serial observational
      follow-up study of clinical and lung function measurements up to 53 months after
      acute illness. SETTING: University pediatric intensive care unit in a national
      children's hospital. PATIENTS: Five critically ill children aged 5-14 years.
      INTERVENTIONS: None RESULTS: Clinical recovery: each patient required a 3-5 month
      convalescence before being able to attend full-time school because of lethargy
      and dyspnea. All patients developed wheeze 3-12 months after illness and four
      received long-term bronchodilator therapy. Lung function recovery: for both the
      forced vital capacity (FVC) and forced vital capacity in the first second (FEV1)
      four patients had abnormally low values, regaining only 60-70% of predicted
      values for their height and sex, and all of this improvement had occurred by 6-12
      months after illness. Beyond this interval, patients remained on their same FVC
      and FEV1 centile. FEV1/FVC ratios were consistently within the normal range,
      indicating a predominantly restrictive defect. Changes in peak expiratory flow
      exhibited a time course of improvement similar to the other lung function tests.
      CONCLUSION: In children, pulmonary recovery after severe AHRF may occur for 6-12
      months. A 1-year follow-up could offer a rational single point for assessment of
      outcome and long-term counselling of child and parents.

PMID- 9660273
TI  - Variation of inhaled nitric oxide concentration with the use of a phasic flow
      ventilator.

PMID- 9660274
TI  - Early prediction of neurologic prognosis after post-anoxic coma.

PMID- 9660275
TI  - Severe noninfectious acute lung injury in early phase of bone marrow
      transplantation.

PMID- 9660276
TI  - Soothing the savage throat.

PMID- 9660277
TI  - Pharyngitis: how can so simple a disease be so complex?

PMID- 9660278
TI  - What is a migraine, anyway, and when is it gone?

PMID- 9660279
TI  - Rethinking gatekeeping: a closer look at its application to emergency medical
      services.

PMID- 9660280
TI  - Clinical wound evaluation scales.

PMID- 9660281
TI  - The role of betamethasone in the treatment of acute exudative pharyngitis.
AB  - OBJECTIVE: To compare betamethasone with placebo as an adjuvant to antibiotic
      therapy in the treatment of acute exudative pharyngitis. METHODS: The study was a
      randomized, doubled-blind, placebo-controlled, single-center, parallel,
      outpatient clinical trial. After consent was obtained, each patient was asked to
      rate his or her pain on a 10-cm numbered visual analog scale (VAS; 0-10). All of
      the patients received injectable benzathine penicillin. If allergic to
      penicillin, they were started on a 10-day course of polyenteric-coated
      erythromycin (PCE). Each patient was randomized to receive either i.m.
      betamethasone or i.m. placebo. All patients were contacted by telephone at 24 and
      48 hours by one of the study investigators and asked to rate their pain based on
      another VAS. If their pain was not resolved by 48 hours, they were called again
      daily between the third and seventh days after the initial visit to determine the
      time of pain resolution. RESULTS: A total of 92 patients were enrolled in the
      study, with 46 randomized to receive placebo and 46 to receive betamethasone.
      Eight patients were excluded from the statistical analysis because of inability
      to obtain follow-up. Demographic comparison showed that gender distributions,
      ages, mean initial pain scores, mean times to the first and second follow-up
      calls, and treatment regimens were similar in the 2 groups. There were
      significantly better pain scores for the betamethasone group at first follow-up
      (p = 0.0005), at second follow-up (p = 0.004), and in number of hours until
      relief of pain (p = 0.004). When only those patients with a positive culture for
      a streptococcus species were analyzed, there also were significant reductions in
      pain score at the first (p = 0.006) and second (p = 0.02) follow-up visits.
      CONCLUSION: Pain relief was greater and more rapid in patients treated with
      betamethasone as an adjuvant therapy in acute exudative pharyngitis.

PMID- 9660283
TI  - Retinal venous oxygen saturation correlates with blood volume.
AB  - OBJECTIVES: To evaluate the sensitivity of retinal venous O2 saturation (SrvO2)
      for early blood loss and reinfusion. A secondary objective was to measure the
      correlation between SrvO2 and mixed venous O2 saturation (SvO2) during blood loss
      and reinfusion. METHODS: Seven anesthetized swine were bled at 0.8 mL/kg/min to
      16 mL/kg. Shed blood was re-infused at the same rate and the swine were allowed
      to equilibrate. After equilibration, repeat hemorrhages were performed at 1.6
      mL/kg/min and 2.4 mL/kg/min. SrvO2 was measured using an eye oximeter (EOX) and
      SvO2 was measured using a fiber-optic catheter. RESULTS: During blood loss, SrvO2
      correlated with blood removed (r = -0.88, -0.97, -0.96) and SvO2 (r = 0.87, 0.98,
      0.92). During reinfusion, SrvO2 correlated with blood re-infused (r = 0.63, 0.76,
      0.82) and SvO2 (r = 0.80, 0.93, 0.96). SrvO2 decreased 1.22 +/- 0.60%/mL/kg of
      blood removed. The rate of decrease in SrvO2 per minute (deltaSrvO2) when blood
      was removed at 2.4 mL/kg/min was significantly greater than deltaSrvO2 when blood
      was removed at 0.8 mL/kg/min (p < 0.007). The rates of change in blood pressure
      (BP) and pulse were not significantly different at any rate of blood removal.
      CONCLUSIONS: In this model, retinal venous O2 saturation correlated with blood
      volume and central venous O2 saturation. Unlike the rate of change in BP and
      heart rate, deltaSrvO2 values were significantly different at different rates of
      blood removal. Use of an EOX to monitor for blood loss, estimate the rate of
      hemorrhage, and evaluate the response to therapy during resuscitation warrants
      further study.

PMID- 9660282
TI  - Intravenous ketorolac vs intravenous prochlorperazine for the treatment of
      migraine headaches.
AB  - OBJECTIVE: To compare i.v. ketorolac with i.v. prochlorperazine as the initial
      treatment of migraine headaches in the ED. METHODS: A prospective, double-blind
      comparison study was performed, using a convenience sample of 64 patients
      suffering from migraine headaches presenting to the ED at a tertiary care
      university teaching hospital. Patients were randomly assigned to receive either
      10 mg of prochlorperazine i.v. or 30 mg of ketorolac i.v.. Patients scored the
      severity of their headaches using a 10-cm visual analog pain scale. An initial
      mark was made on the scale at the time of entry into the study and later another
      mark was made on a new unmarked pain scale 1 hour after medication
      administration. Changes in pain scores within each treatment group and between
      groups were analyzed using the Wilcoxon rank sum test. RESULTS: Prior to
      treatment, the patients assigned to receive prochlorperazine had a median score
      of 9.2 cm (mean +/- SD pain score of 8.3 cm +/- 2.1 cm), while the patients
      receiving ketorolac had a median score of 9.0 (mean pain score of 8.4 cm +/- 1.7
      cm). There was no significant difference between the pain scores of the
      participants in the 2 groups prior to treatment (p = 0.80). One hour after
      medication administration, the patients in the prochlorperazine group had a
      median score of 0.5 cm (mean 2.1 +/- 3.2 cm), while those patients receiving
      ketorolac had a median pain score of 3.9 (mean 4.0 +/- 3.3 cm). The decrease in
      pain score was significant for both groups of patients (p = 0.0001). The change
      in pain score for the patients in the prochlorperazine group (median 7.1) was
      significantly greater than the change in pain score for the patients in the
      ketorolac group (median 4.0; p = 0.04). CONCLUSION: Although both drugs were
      associated with a significant reduction in pain scores, benefit over a placebo
      agent was not tested. Furthermore, the patients who received prochlorperazine
      i.v. for migraine headaches had a statistically significant greater decrease in
      their pain scores than did those receiving ketorolac i.v.

PMID- 9660284
TI  - An assessment of clinical wound evaluation scales.
AB  - OBJECTIVE: To compare 2 clinical wound scales and to determine a minimal
      clinically important difference (MCID) on the visual analog cosmesis scale.
      METHODS: Using data from 2 previously published clinical trials, 91 lacerations
      and 43 surgical incisions were assessed on the 2 scales; a 100-mm visual analog
      scale (VAS) (0 = worst possible scar, 100 = best possible scar) and a wound
      evaluation scale (WES) assessing 6 clinical variables (a score of 6 is considered
      optimal, while a score of < or =5 suboptimal). All wound assessments on the VAS
      were done by 2 cosmetic surgeons who rated photographs on 2 occasions. A cohort
      of wounds on the WES were assessed by a second observer. The difference of the
      mean optimal and suboptimal VAS scores for each study was used to determine a
      MCID on the VAS scale. RESULTS: The VAS scale yielded intraobserver agreements of
      0.93 and 0.87 (95% CI: 0.89-0.96 and 0.78-0.93) and interobserver agreements of
      0.50 and 0.71 (95% CI: 0.32-0.65 and 0.52-0.84) for lacerations and incisions,
      respectively. Kappa coefficient measuring agreement on the WES was 0.79 (95% CI:
      0.57-1.0). The mean (+/-SD) VAS scores of optimal wounds were 72 +/- 12 mm and 65
      +/- 20 mm, while the mean scores of suboptimal wounds were 57 +/- 17 mm and 50 +/
      23 mm for lacerations and incisions, respectively. CONCLUSIONS: An MCID on the
      VAS cosmesis scale is 15 mm. Studies should be designed to have a sample size and
      power to detect this difference.

PMID- 9660285
TI  - Gatekeepers: a missed opportunity for safe transport.
AB  - OBJECTIVE: To assess whether contact with a health care provider or gatekeeper
      increases the use of an ambulance for patients with acute chest pain. METHODS: A
      convenience sample of adults > or =40 years of age presenting with a chief
      complaint of chest pain were interviewed by trained personnel regarding transport
      used to come to the ED. The study was performed at the ED of an urban university
      hospital. Patients with hemodynamic instability and those receiving thrombolytics
      or emergency angioplasty were excluded. Patients were asked about access to a
      primary health care provider and contact with a provider regarding this ED visit,
      including instructions given for transportation. RESULTS: Of the 450 interviewed
      patients, 42% arrived by ambulance. Those who had contact with a health care
      provider prior to the ED visit were less likely to come by ambulance than those
      without contact, 31% vs 51% (p < 0.001). Of the patients who had cardiac enzymes
      obtained to work up for their chest pain, 34% with health provider contact vs 57%
      without health provider contact arrived by ambulance (p < 0.001). Of those with
      acute myocardial infarction, 30% with health provider contact vs 66% without
      health provider contact came by ambulance (p < 0.03). Patients who recalled
      transport instructions from their providers tended to follow those instructions.
      The majority of patients who recalled no specific transport instructions arrived
      by personal automobile. CONCLUSION: Of patients presenting to an ED for
      evaluation of chest pain, those who made contact with a health care provider were
      less likely to arrive via ambulance.

PMID- 9660286
TI  - Advanced life support vs basic life support field care: an outcome study.
AB  - OBJECTIVE: To determine whether the provision of advanced life support (ALS)
      field care has any impact on patient outcome in the urban Canadian environment.
      METHODS: A convenience cohort study was conducted of all emergent ambulance
      transfers of adults to an urban Canadian hospital from May 22 to July 31, 1996.
      Data were collected from ambulance call reports regarding presenting complaint
      and field interventions applied, and from hospital records regarding time in the
      ED, hospital length of stay (LOS), and discharge disposition. Patient outcomes
      were compared within 7 presenting complaint groups (chest pain, altered level of
      consciousness, shortness of breath, abdominal pain, motor vehicle crash, falls,
      and other) by field care level: level 1--BLS (basic life support) vs levels 2 and
      3--ALS. RESULTS: The study population consisted of 1,397 patients. No significant
      differences were seen between BLS and ALS patients on baseline demographics. ED
      triage score did not depend on field care level for any group, implying that
      those in the ALS group were not inherently sicker. Outcome measures (ED LOS,
      admission rates, and hospital LOS) showed no significant differences between BLS
      and ALS for each presenting complaint group. Discharge dispositions were analyzed
      by chi2 but were not varied enough to allow reliable analysis. Observation of
      trends suggested no difference between BLS and ALS. CONCLUSIONS: There was no
      beneficial impact on the measured patient outcomes found in association with the
      provision of ALS vs BLS field care in Metropolitan Toronto for patients who were
      brought to a nontrauma center.

PMID- 9660287
TI  - Parenteral vs oral antibiotics in the prevention of serious bacterial infections
      in children with Streptococcus pneumoniae occult bacteremia: a meta-analysis.
AB  - OBJECTIVE: To determine whether parenteral antibiotics are superior to oral
      antibiotics in preventing serious bacterial infections in children with
      Streptococcus pneumoniae occult bacteremia. METHODS: Using the MEDLINE database,
      the English language literature was searched for all publications concerning
      bacteremia, fever, or Streptococcus pneumoniae from 1966 to January 1, 1997. All
      nonduplicative studies with a series of children with S. pneumoniae occult
      bacteremia having both orally treated and parenterally treated groups were
      reviewed. Children were excluded from individual studies if at the time of their
      initial evaluation they were immunocompromised, had a serious bacterial
      infection, underwent a lumbar puncture, or did not receive antibiotics. RESULTS:
      Only 4 studies met study criteria. From these studies, 511 total cases of S.
      pneumoniae occult bacteremia were identified. Ten of 290 (3.4%) in the oral group
      and 5 of 221 (2.3%) in the parenteral antibiotic group developed serious
      bacterial infections (pooled p-value = 0.467, pooled OR = 1.48; 95% CI, 0.5-4.3).
      Two patients in the oral group (0.7%) and 2 patients in the parenteral group
      (0.9%) developed meningitis (pooled p-value = 0.699, pooled OR = 0.67; 95% CI,
      0.1-5.1). CONCLUSION: The rates of serious bacterial infections and meningitis
      did not differ between children who were treated with oral and parenteral
      antibiotics. The extremely low rate of complications observed in both groups
      suggests no clinically significant difference between therapies. A study with
      >7,500 bacteremic children (or >300,000 febrile children) would be needed to have
      80% power to prove parenteral antibiotics are superior to oral antibiotics in
      preventing serious bacterial infections.

PMID- 9660288
TI  - Detection of alcohol use in adolescent patients in the emergency department.
AB  - OBJECTIVES: To examine 3 methods of detecting alcohol use among adolescent
      patients visiting a Level-1 regional trauma center. METHODS: Part 1 was a
      retrospective review of laboratory records and (13- to 19-year-old) patient
      medical records over the 1-year period from August 1993 to July 1994. Part 2 was
      a review of ICD-9 discharge diagnoses for the same age range during the same 1
      year period. Part 3 involved prospective saliva alcohol testing of injured
      patients aged 13-17 years old. RESULTS: Part 1: A total of 522 blood tests were
      conducted and 160 (30.6%) were positive for alcohol. More than one-third of the
      alcohol-positive sample had alcohol ingestion as the only reason for their
      visits, i.e., they were uninjured. The alcohol-positive group was more likely to
      be male and older. Part 2: A total of 99 alcohol-related discharge diagnoses were
      given to adolescent patients. Alcohol abuse was the most common diagnosis. With
      the 2 methods of detection combined, 186 patients were identified. Part 3: A
      total of 119 saliva alcohol tests were conducted. One patient tested positive but
      had been identified while in triage as having used alcohol. CONCLUSION: In this
      study population, approximately one-third of adolescent patients tested for
      alcohol as part of routine clinical care were alcohol-positive but were not
      necessarily given an alcohol-related diagnosis. Thus, studies determining rates
      of alcohol-positive adolescents treated in EDs should use multiple methods of
      detection. Universal testing does not appear to be warranted for all injured
      adolescent patients.

PMID- 9660289
TI  - The Tokyo subway sarin attack: disaster management, Part 1: Community emergency
      response.
AB  - The Tokyo subway sarin attack was the second documented incident of nerve gas
      poisoning in Japan. Prior to the Tokyo subway sarin attack, there had never been
      such a large-scale disaster caused by nerve gas in peacetime history. This
      article provides details related to how the community emergency medical services
      (EMS) system responded from the viewpoint of disaster management, the problems
      encountered, and how they were addressed. The authors' assessment was that if
      EMTs, under Japanese law, had been allowed to maintain an airway with an
      endotracheal tube or use a laryngeal mask airway without physician oversight,
      more patients might have been saved during this chemical exposure disaster. Given
      current legal restrictions, advanced airway control at the scene will require
      that doctors become more actively involved in out-of-hospital treatment. Other
      recommendations are: 1) that integration and cooperation of concerned
      organizations be established through disaster drills; 2) that poison information
      centers act as regional mediators of all toxicologic information; 3) that a real
      time, multidirectional communication system be established; 4) that multiple
      channels of communication be available for disaster care; 5) that public
      organizations have access to mobile decontamination facilities; and 6) that
      respiratory protection and chemical-resistant suits with gloves and boots be
      available for out-of-hospital providers during chemical disasters.

PMID- 9660291
TI  - The Tokyo subway sarin attack: disaster management, Part 3: National and
      international responses.
AB  - The authors report the national and international responses to the disaster
      produced by the Tokyo subway sarin attack. From a worldwide historical
      perspective, there had never been such a large-scale disaster caused by nerve gas
      during peacetime. Therefore, this event should be studied from various viewpoints
      in cooperation with members of the international community. To this end, the
      Japanese government should help coordinate a large-scale and detailed
      investigation of the Tokyo subway sarin attack, including the long-term effects
      of sarin. The authors also recommend that the Japanese Self Defense Forces should
      be used more effectively in large-scale disasters. The system of direct control
      of disaster management by the Japanese government could be useful in a large
      scale disaster.

PMID- 9660290
TI  - The Tokyo subway sarin attack: disaster management, Part 2: Hospital response.
AB  - The Tokyo subway sarin attack was the second documented incident of nerve gas
      poisoning in Japan. The authors report how St. Luke's Hospital dealt with this
      disaster from the viewpoint of disaster management. Recommendations derived from
      the experience include the following: Each hospital in Japan should prepare an
      emergent decontamination area and have available chemical-resistant suits and
      masks. Ventilation in the ED and main treatment areas should be well planned at
      the time a hospital is designed. Hospital disaster planning must include guidance
      in mass casualties, an emergency staff call-up system, and an efficient emergency
      medical chart system. Hospitals should establish an information network during
      routine practice so that it can be called upon at the time of a disaster. The
      long-term effects of sarin should be monitored, with such investigation ideally
      organized and integrated by the Japanese government.

PMID- 9660292
TI  - End-tidal carbon dioxide monitoring in emergency medicine, Part 1: Basic
      principles.
AB  - End-tidal carbon dioxide (PetCO2) monitoring is becoming more common in both the
      ED and the out-of-hospital setting. Its main use has been as an aid when
      confirming endotracheal intubation. However, since CO2 is intrinsically coupled
      with states of metabolism, circulation, and ventilation, PetCO2 monitoring along
      with analysis of its capnographic component is becoming increasingly valuable for
      other uses in the ED. This article reviews the physiology of CO2, the means by
      which end-tidal CO2 may be monitored, and the components and analysis of the
      capnogram.

PMID- 9660293
TI  - End-tidal carbon dioxide monitoring in emergency medicine, Part 2: Clinical
      applications.
AB  - End-tidal carbon dioxide (PetCO2) monitoring is becoming more common in both the
      ED and the out-of-hospital setting. Its main use has been as an aid when
      confirming endotracheal intubation. Other uses in the ED include monitoring CPR
      efforts and monitoring the ventilatory and hemodynamic status of intubated and
      nonintubated patients. In addition, future uses may include using PetCO2 as an
      adjunct when monitoring the status of asthma treatment, when making the diagnosis
      of pulmonary embolism, and when measuring cardiac output noninvasively. This
      article reviews these specific uses of PetCO2 monitoring in emergency medicine.

PMID- 9660294
TI  - Defibrillation and public expectation--revisited.

PMID- 9660295
TI  - Percentage abnormal results (PAR) as an outcome measure.

PMID- 9660296
TI  - A marine-acquired infection with rapidly progressive cellulitis.

PMID- 9660297
TI  - Tuberculosis screening of residents and staff in long-term care facilities.

PMID- 9660298
TI  - Use of transduced cell lines in studies on alcohol metabolism and toxicity.
      Introduction to the symposium.

PMID- 9660299
TI  - Ethanol oxidation mediates impaired hepatic receptor-mediated enocytosis.

PMID- 9660300
TI  - Studies on the enzymology of aldehyde dehydrogenase-2 in genetically modified
      HeLa cells.
AB  - The Asian flush reaction is known to result from a lysine for glutamine
      substitution in the aldehyde dehydrogenase 2 (ALDH2) gene. This mutation was
      studied in HeLa cells transduced with retroviruses carrying the ALDH2E (wild
      type) and ALDH2K (variant) cDNAs. The cells expressed high levels of the enzyme
      protein that had the same pI and enzymatic characteristics as the corresponding
      liver enzyme. When cells expressing ALDH2E were transduced with ALDH2K expressing
      retrovirus, the ALDH2 activity was reduced roughly in proportion to the amount of
      ALDH2K mRNA expressed, indicating a dominant suppression of activity. The half
      life of the wild-type enzyme was 22 hr, while that of variant enzyme was 14 hr.
      The half-life of the enzyme in cells expressing both cDNAs was 13 hr, indicating
      that the shorter half-life of the variant was also dominant These data are
      consistent with a model in which the wild-type homodimers have normal activity
      and turnover, while the heterodimers have reduced to virtually no activity and
      increased turnover. The model predicts residual ALDH2 activity in heterozygotes
      of about 13% of that in individuals homozygous for ALDH2*1, in good agreement
      with experimentally determined values.

PMID- 9660301
TI  - Cytotoxicity and apoptosis produced by arachidonic acid in HepG2 cells
      overexpressing human cytochrome P-4502E1.
AB  - The goal of the current study was to evaluate the effects of arachidonic acid, as
      a representative polyunsaturated fatty acid, on the viability of a HepG2 cell
      line, which has been transduced to express human cytochrome P4502E1 (CYP2E1).
      Arachidonic acid produced a concentration- and time-dependent toxicity to HepG2
      MV2E1-9 cells, which express CYP2E1, but little or no toxicity was found with
      control cells. In contrast to arachidonic acid, oleic acid was not toxic to the
      HepG2-MV2E1-9 cells. The cytotoxicity of arachidonic acid involved a lipid
      peroxidation type of mechanism since toxicity was enhanced after depletion of
      cellular glutathione; formation of malondialdehyde and 4-hydroxy-2-nonenal was
      markedly elevated in the cells expressing CYP2E1, and toxicity was prevented by
      antioxidants and the iron chelator desferrioxamine. The CYP2E1-dependent
      arachidonic acid toxicity appeared to involve apoptosis, as demonstrated by
      terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling and DNA
      laddering experiments. Trolox, which prevented toxicity of arachidonic acid, also
      prevented the apoptosis. Transfection with a plasmid containing bcl-2 resulted in
      complete protection against the CYP2E1-dependent arachidonic acid toxicity. It is
      proposed that elevated production of reactive oxygen intermediates by cells
      expressing CYP2E1 can cause lipid peroxidation, which subsequently promotes
      apoptosis and cell toxicity when the cells are enriched with polyunsaturated
      fatty acids such as arachidonic acid.

PMID- 9660302
TI  - Use of transfected liver cells to evaluate potential mechanisms of alcohol
      induced liver injury.
AB  - There is increased activity of the proinflammatory cytokine, tumor necrosis
      factor (TNF) in alcoholic liver disease (ALD). Hepatic neutrophil infiltration is
      a principal injurious manifestation of ALD. TNF can induce cellular oxidative
      injury directly, and indirectly by inducing neutrophil chemotactic factor (IL-8)
      production by hepatocytes. IL-8 activates and chemotactically attracts
      neutrophils to the liver where they release oxidizing substances. Patients with
      ALD also have decreased protective factors for cellular oxidative injury.
      Manganous superoxide dismutase (MnSOD) is an antioxidant protective factor. The
      objectives of these studies were to investigate mechanisms for induction of an
      injurious factor (IL-8) and a protective factor (MnSOD) in the HepG2 human
      hepatoma cell line. In the first set of experiments, IL-8 gene reporter
      constructs were used to transiently transfect a derivative (MVh2E1-9) of the
      HepG2 cell line which expresses P-4502E1 and metabolizes ethanol. Inactivation of
      the NF-kappaB and 3'NF-IL-6 DNA binding sites decreased IL-8 gene transcriptional
      activation in response to TNF while inactivation of the 5'NF-IL-6 binding site
      increased IL-8 gene transcriptional activity in response to TNF. This system may
      be useful to assess the effects of ethanol on TNF-induced hepatocyte IL-8
      production. In the second set of experiments, HepG2 cells were cultured in 25 to
      100 mmol concentrations of ethanol. Both TNF and ethanol increased HepG2 cell
      MnSOD activity in short-term (72 hr) cultures with ethanol. However, after long
      term (10 weeks) culture with ethanol, there was no induction of MnSOD by ethanol
      and there was a diminished induction of MnSOD in response to TNF. Further studies
      are needed to assess the effect of this diminished induction of MnSOD with
      chronic ethanol culture on HepG2 cell susceptibility to TNF cytotoxicity. We
      conclude that transfected liver cell lines can be used to evaluate mechanisms for
      increased injurious factors and decreased protective factors in alcoholic liver
      injury.

PMID- 9660303
TI  - Acute alcohol effects on opiomelanocortinergic regulation.
AB  - To assess acute effects of alcohol on forebrain and pituitary
      opiomelanocortinergic regulation, a model was developed in which "experienced"
      (previously introduced to ethanol administration, so the subjective response was
      not a novel stimulus) male Sprague-Dawley rats received pulsatile intragastric
      ethanol infusions during the dark (active) photophase to produce and sustain (for
      3 hr) behaviorally relevant (0, 40 to 70, 80 to 110, or 120 to 150 mg/dl) plasma
      ethanol levels. The effects of alcohol on hypothalamo-pituitary-adrenal (H-P-A)
      axis function were biphasic with respect to dosage (inhibition with low dosage
      and stimulation with higher dosages) and time (initial stimulation with higher
      dosages was followed by rapid return to control levels even though elevated
      plasma ethanol levels were maintained). The effects of alcohol on H-P-A
      activation were also inconsistent; some of the animals did not appear to respond
      even though elevated (i.e., >100 mg/dl) plasma ethanol levels were produced.
      Induction of moderate (80 to 110 mg/dl) plasma ethanol levels acutely (within 30
      min) increased immunoreactive (i) beta-endorphin concentrations in the ventral
      tegmental area of the brain; higher (120 to 150 mg/dl) plasma ethanol levels
      increased i beta-endorphin concentrations in both the ventral tegmental area and
      the nucleus accumbens, whereas i beta3-endorphin concentrations were not
      significantly altered in other brain areas. High (120 to 150 mg/dl) plasma
      ethanol levels also increased mediobasohypothalamic pro-opiomelanocortin
      (biosynthetic precursor of forebrain beta-endorphin) mRNA concentrations at 3 and
      6 hr after initiation of ethanol infusions. Results demonstrate that atraumatic
      induction of physiologically meaningful plasma alcohol levels by gastric ethanol
      infusion activates the forebrain opiomelanocortinergic opioid system and exerts
      complex effects on the interrelated H-P-A system, consistent with evidence that
      these systems may interact to mediate or modulate some responses to alcohol
      ingestion.

PMID- 9660304
TI  - Mechanism of action of acamprosate. Part I. Characterization of spermidine
      sensitive acamprosate binding site in rat brain.
AB  - It has been suggested that the anticraving drug, acamprosate, acts via the
      glutamatergic system, but the exact mechanism of action is still unknown. The aim
      of this study was to characterize [3H]acamprosate binding and establish whether
      this showed any relation to sites on the NMDA receptor complex. We found
      saturable specific binding of [3H]acamprosate to rat brain membranes with a KD of
      120 microM and a Bmax of 450 pmol/mg of protein. This acamprosate binding site
      was sensitive to inhibition by spermidine (IC50: 13.32 +/- 1.1 microM; Hill
      coefficient = 1.04), and arcaine and glutamate both potentiated the inhibitory
      effect of spermidine. Acamprosate binding to the acamprosate binding site was
      also sensitive to inhibition by divalent cations (Ca2+, Mg2+, and Sr2+).
      Conversely, acamprosate displaced [14C]spermidine binding from rat brain
      membranes with an IC50 of 645 microM and a Hill coefficient = 1.74. This
      inhibitory effect of acamprosate was not affected by arcaine, and was associated
      with a significant reduction in Bmax and binding affinity for spermidine,
      suggesting an allosteric interaction between acamprosate and a spermidine binding
      site. These data are consistent with an effect of acamprosate on the NMDA
      receptor protein complex, and acamprosate was also found to alter binding of
      [3H]dizocilpine to rat brain membranes. When no agonists were present in vitro
      (minimal NMDA receptor activation), acamprosate markedly potentiated
      [3H]dizocilpine binding at concentrations in the 5 to 200 microM range. However,
      under conditions of maximal receptor activation (100 microM glutamate, 30 microM
      glycine), acamprosate only inhibited [3H]dizocilpine binding (at concentrations
      concentrations >100 microM). When these binding studies were performed in the
      presence of 1 microM spermidine, the enhancing effects of acamprosate on
      [3H]dizocilpine binding were inhibited. The results show that acamprosate binds
      to a specific spermidine-sensitive site that modulates the NMDA receptor in a
      complex way. Together, with data from al Quatari et al. (see next paper), this
      work suggests that acamprosate acts as "partial co-agonist" at the NMDA receptor,
      so that low concentrations enhance activation when receptor activity is low,
      whereas higher concentrations are inhibitory to high levels of receptor
      activation. This may be relevant to the clinical effects of acamprosate in
      alcohol-dependent patients during abstinence.

PMID- 9660305
TI  - Mechanism of action of acamprosate. Part II. Ethanol dependence modifies effects
      of acamprosate on NMDA receptor binding in membranes from rat cerebral cortex.
AB  - Acamprosate is a putative anticraving drug used to maintain abstinence in alcohol
      dependent patients. Its mechanism of action is uncertain, but the drug is thought
      to interact with neuronal NMDA receptors and calcium channels, and these proteins
      are implicated in the induction of alcohol dependence. In these experiments, the
      effects of acamprosate were studied on the binding of the NMDA receptor ligand
      [3H]dizocilpine to rat brain membranes under nonequilibrium conditions; 10 microM
      glutamate and 1 microM glycine were present in the binding assays to partially
      activate the receptor. At clinically relevant concentrations (in the micromolar
      range), acamprosate significantly enhanced [3H]dizocilpine binding to cortical
      membranes from control animals (suggesting that acamprosate may increase the rate
      of association of the radioligand), whereas at higher concentrations binding was
      inhibited. This effect is consistent with a partial agonist effect of acamprosate
      on the NMDA receptor protein. However, when rats were made dependent on ethanol
      (exposure to the drug for 10 days by inhalation) and cortical membranes were
      prepared from these animals, acamprosate in vitro no longer produced any
      enhancement of [3H]dizocilpine binding. Similar results were obtained when
      membranes were used from rats that had received 400 mg/kg/day of acamprosate in
      their drinking water with or without concurrent ethanol inhalation for 10 days.
      Thus, in brain membranes from all these treatment groups, acamprosate in vitro
      caused inhibition of [3H]dizocilpine binding only. The results suggest that
      acamprosate may have excitatory or inhibitory effects on NMDA receptors,
      depending on the experimental conditions. The effects of the drug on this system
      appear to be shifted toward inhibition in alcohol dependence, and this finding
      may be important to its clinical mechanism.

PMID- 9660306
TI  - GABA(A) receptor alpha1, alpha4, and beta3 subunit mRNA and protein expression in
      the frontal cortex of human alcoholics.
AB  - Animal studies have shown that chronic ethanol consumption produces physical
      dependence upon ethanol and alters gamma-aminobutyric acid-A (GABA(A)) receptor
      subunit gene expression in brain. Although extensive investigation has been
      conducted in animal models, relatively little work has been performed directly on
      human alcoholic brain tissue to determine if there are alterations in GABA(A)
      receptor gene expression. In this study, GABA(A) receptor alpha1, alpha4, and
      beta3 subunit mRNA and peptide expression in postmortem frontal cortex from human
      alcoholics (n = 15) and age- and sex-matched controls (n = 13) were measured by
      quantitative, competitive reverse transcription polymerase chain reaction and
      Western blot analysis. GABA(A) receptor beta3 subunit mRNA expression was 35%
      greater (p < 0.05) in alcoholics, compared with nonalcoholic controls. We found
      no significant difference in alpha1 and alpha4 subunit mRNA levels between
      groups. However, there was a trend toward greater (21%) alpha1 subunit mRNA
      expression. There was no difference in alpha1, alpha4, or beta2/3 subunit peptide
      levels in frontal cortex between controls and alcoholics. Neither the age of the
      subjects nor the postmortem interval correlated with mRNA or peptide levels.
      Blood ethanol content also did not correlate with mRNA or peptide expression in
      alcoholic samples. These data suggest that GABA(A) receptor adaptations,
      resulting from prolonged alcohol consumption in human alcoholics, may differ from
      animal models of alcohol dependence. These differences may be related to the
      longevity of alcohol exposure in human alcoholics, as well as variability in the
      dependence/withdrawal state of the human subjects. Therefore, further studies in
      human postmortem brain tissue are warranted.

PMID- 9660307
TI  - Modulation of the insulin-like growth factor system by chronic alcohol feeding.
AB  - Insulin-like growth factor (IGF)-I is a potent anabolic agent that plays an
      important role in regulating muscle protein balance. Alterations in one or more
      of the various components of the IGF system may be in part responsible for the
      muscle wasting that accompanies chronic alcohol consumption. The purpose of the
      present study was to characterize changes in the growth hormone-IGF axis produced
      by chronic alcohol consumption in rats. After 8 weeks of alcohol feeding, the IGF
      I concentration was decreased in plasma (31%) as well as in the liver and
      skeletal muscle (40-50%), compared with pair-fed control animals. In addition,
      alcohol consumption decreased IGF-I mRNA abundance in liver and muscle
      (approximately 50%). IGF-I content in duodenum and kidney, however, was not
      altered by alcohol feeding. Concomitantly, the relative concentration of IGF
      binding protein (IGFBP)-1 was increased in plasma, liver, and muscle of alcohol
      fed rats, compared with control values. In contrast, no changes in the plasma
      concentrations of IGFBP-2, -3, or -4 were detected in alcohol-fed rats at this
      time point Previous studies have indicated that elevations in glucocorticoids or
      decreases in insulin or growth hormone might be responsible for the decrease in
      IGF-I and/or the increase in IGFBP-1 in other catabolic conditions. However,
      there was no difference in the plasma concentrations of these hormones between
      alcohol-fed and control animals in this study. These data indicate that chronic
      alcohol feeding in rats decreases IGF-I and increases IGFBP-1 in the circulation
      and in skeletal muscle and that these changes appear to be independent of changes
      in classical hormonal regulators of the IGF system. The observed alterations in
      the IGF system are consistent with a reduction in the anabolic actions of IGF-I
      induced by chronic alcohol consumption.

PMID- 9660308
TI  - Sex differences in voluntary drinking by Long Evans rats following early stress.
AB  - Models for early stress and voluntary drinking were used to determine the
      contribution of early stress to increased intake of alcoholic beverages during
      puberty and adulthood. Newborn litters of Long Evans rats were: (1) stressed by
      daily separation from the mother for 15 min/day on days 1 to 7 of life ["handled"
      (H)]; or (2) left untouched with the mother on days 1 to 7 of life ["nonhandled"
      (NH)]. All animals were weaned on day 22, separated by sex (M and F), and caged
      individually with an assignment of 10 animals per sex per treatment group (H and
      NH). From 25 to 85 days of age, all animals were given free access to beer
      containing 5% ethanol (v/v), water, and regular laboratory food. Beer, food, and
      water intake was measured daily at the same time each day, and animals were
      weighed weekly. HM had greater ethanol intake and preference for ethanol during
      the peripubertal period (days 32 to 45), compared with all other groups. There
      were no differences in ethanol intake between NHF and NHM. HM had greater ethanol
      preference than HF on 22 of the 60 drinking days. HF consumed the same amount of
      water as the males and significantly greater amounts of water than NHF on 28 of
      the 60 drinking days. HM had greater ethanol preference than NHM on 8 of the 60
      drinking days. From day 75 to day 85, HF had greater ethanol intake than HM, and
      NHF had greater ethanol intake than NHM. There were no differences in body
      weights of HF and NHF throughout the study. Growth of HM lagged behind NHM into
      adulthood. Early stress of males was linked to increased ethanol intake during
      the peripubertal and adult periods and stunted body growth into adulthood. Early
      stress of females was linked to polydipsia (water) throughout development and
      continuing into adulthood, and to increased alcohol intake in adulthood.

PMID- 9660309
TI  - Do taste factors contribute to the mediation of ethanol intake? Ethanol and
      saccharin-quinine intake in three rat strains.
AB  - Several recent studies have suggested that ethanol-preferring rodents may also
      have an affinity for sweet solutions (saccharin, sucrose) and, conversely, that
      saccharin preference may predict ethanol preference. The purpose of the present
      investigation was to determine whether intake of ethanol and saccharin-quinine
      (SQ) solutions would be related in three nonselected strains of rats who differ
      in their ethanol preference: Lewis, Wistar Kyoto, and Wistar. In the first phase
      of the experiment, all animals were presented with an ascending series of ethanol
      solutions (2 to 10%) in free choice with water, followed by a 10-day maintenance
      period of 10% ethanol with water. In the second phase, the same animals were
      presented with an ascending series of SQ solutions (saccharin: 0.4%, quinine:
      0.001 to 0.04%) in free choice with water, followed by a 10-day maintenance
      period of 0.4% saccharin with 0.04% quinine and water. The results revealed an
      absence of a direct relationship between ethanol and SQ consumption. The ethanol
      nonpreferring Lewis rats showed a greater preference for the SQ solutions than
      Wistar Kyoto rats, whereas the ethanol-preferring Wistar Kyoto strain
      consistently consumed significantly less SQ. Wistar rats showed relatively stable
      consumption levels for both solutions that fell between those of the other two
      strains. These results suggested that the relationship between ethanol and SQ
      preference in rats was not a direct one and did not support the findings in the
      literature of a simple overall positive relationship between sweet and ethanol
      preference. These data do, however, provide further evidence for taste factors in
      the mediation of self-selection of ethanol in rats.

PMID- 9660310
TI  - Association study between the -141C Ins/Del and TaqI A polymorphisms of the
      dopamine D2 receptor gene and alcoholism.
AB  - Dopamine D2 receptors have been implicated in the biology of alcohol preference.
      We examined the -141 C Ins/Del polymorphism in the promoter region of the
      dopamine D2 receptor gene (DRD2) and the DRD2 TaqI A polymorphisms in 209
      Japanese alcoholics and 152 age- and sex-matched Japanese controls. The Ins
      allele was significantly increased in the alcoholics, compared with the controls
      (p < 0.002, odds ratio = 1.82). The TaqI A1 allele tended to be more frequent in
      the alcoholics than in the controls (p < 0.04). Linkage disequilibrium between
      these two polymorphisms was weak (a maximum delta value = 0.13). The -141 C
      Ins/Del polymorphism may affect the vulnerability for alcoholism presumably
      through different expression of DRD2 in the Japanese.

PMID- 9660311
TI  - Ethanol transcriptionally upregulates t-PA and u-PA gene expression in cultured
      human endothelial cells.
AB  - Epidemiological studies have suggested that moderate alcohol consumption reduces
      the risk of cardiovascular mortality. This cardioprotective benefit may be
      mediated, in part, by promoting fibrinolysis through changes in fibrinolytic
      components and/or activity, resulting in the decreased risk for thrombosis,
      coronary artery disease, and eventual myocardial infarction. Endothelial cells
      (ECs) play a pivotal role in maintaining normal hemostasis by regulating
      fibrinolysis through the synthesis of plasminogen activators (PAs), tissue-type
      plasminogen activator (t-PA), and urokinase-type plasminogen activator (u-PA).
      The studies described herein were conducted to determine whether a single brief
      preincubation (1 hr, 37 degrees C) of cultured human umbilical vein ECs (HUVECs)
      with low ethanol (0.1%, v/v), will upregulate t-PA and/or u-PA gene expression at
      the transcriptional level, using a combination of nuclear transcription run-on
      assays and transient transfections of cultured HUVECs with the pPA/luc promoter
      constructs. Nuclear run-on assays showed approximately 2- to 3-fold and
      approximately 6- to 7-fold increase in the transcription of new t-PA and u-PA
      mRNAs, respectively. In addition, transient transfections of cultured HUVECs with
      the pt-PA363/luc and pu-PA236/luc promoter constructs, using lipofectamine,
      demonstrated approximately 4- to 6-fold and approximately 6- to 9-fold increase
      in luciferase activity for t-PA and u-PA, respectively. These combined results
      demonstrate that low ethanol transcriptionally upregulates both t-PA and u-PA
      gene expression in cultured HUVECs and provides a molecular basis for the ethanol
      induced increase in EC-mediated fibrinolytic activity that may underlie and
      contribute, in part, to the cardioprotective benefit associated with moderate
      alcohol consumption.

PMID- 9660312
TI  - VTA dopamine neuron activity distinguishes alcohol-preferring (P) rats from
      Wistar rats.
AB  - The mesolimbic dopamine (DA) system is innately deficient in rats selectively
      bred for high alcohol drinking behavior compared with rats selectively bred for
      low alcohol drinking and unselected rats. In alcohol-preferring (P) rats,
      compared with alcohol-nonpreferring (NP) rats, this is evidenced by fewer DA
      neurons in the ventral tegmental area (VTA) projecting to the nucleus accumbens
      (ACB). Yet, despite this deficiency, DA release in the ACB is similar in P, NP,
      and Wistar rats. DA release is regulated by DA neuronal activity, and DA neurons
      fire tonically as well as in bursts. Burst firing has been shown to substantially
      enhance DA release compared with tonic firing. The present study was designed to
      test the hypothesis that the remaining VTA DA neurons in P rats have faster
      firing frequencies and/or burst fire more frequently than VTA DA neurons in
      Wistar rats. The spontaneous activity of VTA DA neurons was recorded in
      unanesthetized alcohol-naive P and Wistar rats. A conventional burst analysis on
      500 consecutive action potentials revealed that P rats had a significantly (p <
      0.05) greater percentage of action potentials in bursts when compared with Wistar
      rats (P: 50.9%, Wistar: 34.4%). Firing frequency and other burst parameters
      (burst interspike interval, burst length, interburst interval, and the number of
      action potentials per burst) did not distinguish the two groups of rats. The
      increased burst activity in P rats may represent a compensatory mechanism to
      maintain adequate basal levels of DA despite the deficiency in the mesolimbic DA
      system.

PMID- 9660313
TI  - Quantitative microdialysis of ethanol in rat striatum.
AB  - We have applied a steady-state theory of microdialysis to characterize the
      diffusion of ethanol through a microdialysis membrane and through rat striatum.
      Quantitative characterization required measurement of in vitro and in vivo
      extraction fractions for ethanol and determination of the clearance of ethanol
      from brain tissue during steady-state perfusion through a microdialysis probe.
      Extraction fraction of ethanol was determined in vitro by perfusing a known
      concentration of ethanol through probes immersed in water at 37 degrees C with
      stirring. The in vitro extraction fraction yielded a probe permeability value of
      0.046 +/- 0.004 cm/min that is comparable with an estimate from published
      measurements for similar dialysis membranes. The in vivo extraction fraction was
      determined for probes placed in the striatum. Clearance of ethanol and a brain
      slice concentration profile of ethanol were determined by measurement of the
      amount of ethanol remaining in the brain tissue during steady-state perfusion of
      the probe. Steady state was achieved within 10 min after beginning the ethanol
      perfusion in vivo, and the extraction fraction was not altered by sedation of the
      rat with pentobarbital. The tissue concentration profile was symmetrical around
      the probe track, and ethanol was detected 1 mm from the probe. The experimental
      clearance rate constant value obtained for ethanol (2.0 +/- 0.3 min(-1)) was
      higher than that expected for removal solely by loss to the blood. The tissue
      diffusivity for ethanol, Dt, derived from the experimental measurements was 1.2
      +/- 0.2 x 10(-5) cm2/sec. This value is greater than expected for interstitial
      diffusion, suggesting a substantial contribution by transcellular diffusion of
      ethanol as well. The predicted tissue concentration profile had a higher peak
      value and did not extend into the tissue (0.5 mm) as much as the experimental
      profile (1 mm), although there was reasonable agreement between experiment and
      theory. Our quantitative characterization of the microdialysis behavior of
      ethanol in brain provides a framework for interpretation of brain microdialysis
      experiments using ethanol by supplying, inter alia, a means for estimating the
      ethanol concentration achieved in the tissue volume being sampled by the probe.

PMID- 9660314
TI  - Prenatal ethanol exposure induces a sexually dimorphic effect on daily water
      consumption in prepubertal and adult rats.
AB  - Previous studies have shown that female rats consume significantly more water
      than males on a weight basis. Because exposure to alcohol during the last week of
      gestation is associated with incomplete behavioral defeminization in male rats,
      we examined daily water intake in fetal alcohol-exposed (FAE) males and females.
      Time-pregnant multiparous Sprague-Dawley dams were administered an ethanol liquid
      diet containing 35% ethanol-derived calories from day 14 through parturition. At
      80 days of age, daily water consumption of FAE males and female litter
      representatives was measured for 7 days. FAE males, but not females, consumed
      significantly more water than their pair-fed counterparts. Subsequent experiments
      determined that the increased water consumption in FAE males is present
      prepubertally, persists into mature adulthood, and is not influenced by prenatal
      or postnatal castration. Chronic estrogen treatment induced large increases in
      water consumption, but consumption of FAE males remained elevated over elevated
      pair-fed male consumption, indicating that pituitary sensitivity to estrogen was
      not increased in FAE males. Morphometric studies of hypothalamic nuclei
      containing vasopressin cells revealed no long-term effects of prenatal ethanol
      exposure on the volume of the supraoptic nucleus or paraventricular nucleus in
      males, nor was an effect observed in the ventromedial nucleus measured as a
      control. In FAE females, the volume of the paraventricular nucleus was
      significantly smaller than chow-fed controls. Whereas baseline plasma and
      pituitary arginine vasopressin (AVP) levels of FAE animals and pair-fed controls
      were not significantly different, AVP content was significantly reduced in the
      septal/bed nucleus region in brains of FAE animals of both sexes. Overall, these
      data indicate that prenatal ethanol exposure increases male water consumption in
      the absence of alterations in basal plasma AVP.

PMID- 9660315
TI  - Skeletal muscle ribonuclease activities in chronically ethanol-treated rats.
AB  - Alcoholic myopathy occurs in up to two thirds of alcohol misusers and is
      characterized by selective atrophy of type II (anaerobic, fast-twitch) fibers;
      type I (aerobic, slow twitch) fibers are relatively unaffected. Both clinical and
      animal studies have indicated that skeletal muscle RNA content is reduced in
      response to ethanol exposure, and contributes to impaired protein synthesis. We
      hypothesized that the reduction in muscle RNA may be due to raised ribonuclease
      (RNase) activities that enhance RNA catabolism. To test this hypothesis, we
      measured the total tissue and plasma RNase activities as well as the activities
      of general (RNase A) and specific or "restriction" RNases (T1L, T2L) in ethanol
      treated rats. Chronically treated rats were fed a nutritionally complete liquid
      diet with 35% of calories as ethanol. Weight-matched controls were pair-fed with
      isocaloric glucose. Rats were killed at time-points up to 6 weeks. For
      comparative purposes, the effect of acute (24 hr) starvation was also analyzed in
      a second group of rats relative to a group of control rats allowed free access to
      food and water over 24 hr. Results showed that the type II fiber-predominant
      plantaris muscle exhibited a significant increase in total RNase, RNase A and
      RNase T1L activities (increases ranged from +59% to +196%; P-values between 0.025
      and 0.01) concomitant with large falls in RNA and protein content. In contrast,
      none of the RNase activities measured in the type I fiber-predominant soleus
      muscles were significantly affected; compositional changes were also smaller in
      the soleus. This effect was independent of reduced nutrition. In conclusion, the
      raised total RNase, RNase A and RNase T1L activities may contribute to the type
      II fiber-specific reduction in total RNA in chronically ethanol-treated rats. In
      turn, this may contribute to the alterations in cellular protein metabolism seen
      under these treatments.

PMID- 9660316
TI  - A quantitative trait locus for alcohol consumption in selectively bred rat lines.
AB  - Selective breeding for high and low alcohol consumption led to the establishment
      of alcohol-preferring (P) and alcohol-nonpreferring (NP) rat lines that differ
      greatly in their alcohol consumption. These lines were inbred and F2 intercross
      progenies were generated to detect quantitative trait loci (QTLs) influencing
      alcohol consumption. A QTL on chromosome 4 was identified with a maximum lod
      score of 8.6. This QTL acts in an additive fashion and accounts for 11% of the
      total phenotypic variability and approximately one-third of the genetic
      variability. Neuropeptide Y, an endogenous anxiolytic and neuromodulator, has
      been mapped to this same region of chromosome 4. This study is an advance in
      genome analyses, demonstrating that crosses between divergent, selectively bred
      rat lines can be used to identify QTLs. Localization of a gene influencing
      alcohol consumption may have important implications for the etiology of alcohol
      abuse and alcoholism in humans.

PMID- 9660317
TI  - Association studies of polymorphisms of CYP2E1 gene in alcoholics with cirrhosis,
      antisocial personality, and normal controls.
AB  - To determine the role of CYP2E1 gene in susceptibility to alcoholism and alcohol
      cirrhosis, we gentoyped a sample of alcoholics with and without cirrhosis,
      alcoholics with antisocial personality, alcoholic families, and normal controls
      with RsaI, PstI, and DraI polymorphisms in the gene. Relative risk and haplotype
      relative risk approaches were used in genotype data analysis. The PstI
      polymorphism data were excluded from further analysis due to strong linkage
      disequilibrium with RsaI. For the RsaI polymorphism, comparison of total
      alcoholics, alcoholics with and without cirrhosis, and alcoholics with antisocial
      personality with normal controls were negative. The results of the same analysis
      with the above groups for DraII were also negative. Using the haplotype relative
      risk method, the result for DraI was positive, meaning that the mutated allele
      (D2) was significantly more transmitted than nontransmitted. However, the result
      of the same analysis for the RsaI polymorphism was not statistically significant.
      We conclude that the CYP2E1 gene plays no substantial role in susceptibility to
      alcohol cirrhosis or alcoholism.

PMID- 9660318
TI  - Carbohydrate-deficient transferrin and conventional alcohol markers as indicators
      for brief intervention among heavy drinkers in primary health care.
AB  - Brief intervention is a promising treatment for heavy drinking. The present study
      examined the diagnostic value of carbohydrate-deficient transferrin (CDT), mean
      corpuscular volume (MCV), aspartate aminotransferase (AST), alanine
      aminotransferase (ALT), and gamma-glutamyltransferase (GGT) in detecting early
      phase heavy drinkers for brief intervention treatment in primary health care.
      Laboratory data were collected from consecutive 20- to 60-year-old, early-phase
      heavy drinkers (329 males and 136 females), who were willing to undergo brief
      intervention treatment in five primary health care outpatient clinics. An
      elevated value of at least 1 of the 5 markers studied was found in 75% of the
      male and in 76% of the female heavy drinkers. The sensitivities of CDT, MCV, AST,
      ALT and GGT values were low; in men, respectively, 39%, 28%, 12%, 28%, and 33%,
      and in women 29%, 40%, 20%, 29%, and 34%. However, marker combinations, including
      CDT, reached a good level of sensitivity; the best triple combination (CDT or MCV
      or GGT) was positive in 69% of the men and 70% of the women. According to
      logistic regression, the age of the patient had an increasing effect on MCV, ALT
      and GGT. High body mass index increased all transaminases and decreased CDT and
      MCV. Smoking increased MCV and decreased AST. Thus, primary health care marker
      combinations, especially those including CDT, should be considered for the
      detection of early-phase heavy drinkers for brief intervention treatment.

PMID- 9660319
TI  - Activated lymphocytes (CD25+ CD69+ cells) and decreased CD19+ cells in well
      nourished chronic alcoholics without ethanol-related diseases.
AB  - To assess lymphocyte subsets and expression of activation antigens in peripheral
      blood lymphocytes (PBLs) in chronic alcoholism, a cross-sectional study with 30
      well-nourished chronic alcoholics and 30 controls was performed. Studies included
      detailed clinical and laboratory evaluation, nutritional status assessment, and
      determination of lymphocyte subpopulations, as well as activation antigens. A
      significant decrease of B cells (CD19+) was observed in chronic alcoholics,
      compared with controls (p < 0.001). A significant increase of PBLs expressing
      CD69 and CD25 (p < 0.01, both) in chronic alcoholics was also detected, whereas
      CD71 expression was unaffected. In addition, T lymphocytes expressing HLA-DR were
      significantly higher in chronic alcoholics than controls (p < 0.05). The serum
      level of soluble interleukin-2 receptor was also significantly higher in the
      alcoholic group, compared with controls (p = 0.04). Moreover, the estimated total
      lifetime dose of ethanol consumed correlated positively with the percentage of
      PBLs expressing CD25 (r = 0.48; p = 0.01) and negatively with PBLs expressing
      CD71 (r = -0.39; p = 0.04). By contrast, the changes were not related to age,
      nutritional status, or the presence of other ethanol-related diseases. In
      conclusion, chronic alcoholics present a significant decrease of B cells and an
      "incomplete activation state" of PBLs that depends on the dose of ethanol
      consumed.

PMID- 9660320
TI  - Anger in an inpatient treatment sample of chronic alcoholics.
AB  - Four measures of anger were investigated in sober male and female alcoholics and
      nonalcoholic peers. The relationships among anger variables, past drinking
      behavior, and substance abuse consequences in alcoholics were explored.
      Additionally, the interrelationships among anger, depression, and anxiety in the
      groups were examined, and the relationships between an overall dysphoria index
      and drinking behavior and substance abuse consequences were determined. 104
      alcoholics (sober 21 to 45 days) and 70 community controls, aged 21 to 56, were
      given the Spielberger Anger Expression Inventory, the Beck Depression Inventory,
      and the Spielberger State Anxiety Inventory. Alcoholics scored higher than
      controls on Trait Anger, Anger-In, and Anger-Out, but not on State Anger. There
      were no main effects of sex. Anger-In was significantly negatively correlated
      with the Quantity-Frequency Index in alcoholic males. Anger-In was significantly
      positively correlated with depression in male and female alcoholics and with
      substance abuse consequences in the latter group. The depression measure was
      significantly correlated with consequences in female, but not in male alcoholics.
      These data have treatment implications, especially for female alcoholics.

PMID- 9660321
TI  - The specificity of the CDT assay in general practice: the influence of common
      chronic diseases and medication on the serum CDT concentration.
AB  - Early recognition of alcohol problems by general practitioners might be enhanced
      by the use of better alcohol markers. Several studies have revealed promising
      results for the carbohydrate-deficient transferrin (CDT) assay in certain
      populations. The aim of our study was to examine the specificity of the CDT assay
      in a general practice population. The main research question was whether common
      chronic diseases and/or the accompanying prescribed drugs have a negative
      influence on the specificity of the CDT assay. The 524 men who participated were
      selected from seven general practices and were suffering from one or more of the
      following diseases: hypertension, asthma/bronchitis, diabetes mellitus,
      adipositis/lipid metabolism disorder, angina pectoris, depression, and disorders
      of the digestive tract. None of the studied diseases or of the accompanying
      prescribed drugs had an influence on the specificity of the CDT assay. The
      overall specificity in this general practitioner population was 0.92. It can be
      concluded that the studied diseases do not bear an influence on the serum CDT
      concentration, and that, therefore, the CDT assay is a highly specific instrument
      for use in assessing alcohol consumption in general practice patients.

PMID- 9660322
TI  - Effect of fetal alcohol exposure on adult symptoms of nicotine, alcohol, and drug
      dependence.
AB  - OBJECTIVES: The objective of this study is to examine the effect of fetal alcohol
      exposure on later substance dependence using an adoption study method. METHODS:
      One hundred ninety-seven adoptees were interviewed for substance abuse disorders,
      including nicotine, alcohol, and drug dependence. Twenty-one adoptees had mothers
      who drank during pregnancy. Adoptees with fetal alcohol exposure were compared
      with those without fetal alcohol exposure for symptoms of adult nicotine,
      alcohol, and drug dependence. RESULTS: Adoptee symptom counts for alcohol, drug,
      and nicotine dependence were higher for those exposed to alcohol in utero. The
      effect of fetal alcohol exposure remained after controlling for gender,
      biological parent alcohol dependence diagnosis, birth weight, gestational age and
      other environmental variables. CONCLUSIONS: Fetal alcohol exposure may produce
      increased risk for later nicotine, alcohol, and drug dependence. Possible effects
      of fetal alcohol exposure on development of adult substance use patterns needs
      attention in genetic studies of substance abuse.

PMID- 9660323
TI  - Work control, work demands, and work social support in relation to alcoholism
      among young men.
AB  - OBJECTIVES: The aim of the study was to estimate the impact of psychosocial work
      environment factors, such as low work control, on alcoholism among young men.
      METHODS: Data on circumstances during childhood and adolescence, such as on risk
      use of alcohol, were collected for 49,323 young men, born 1949 to 1951 at time of
      enlistment for compulsory military training in 1969/1970. On the basis of census
      data on occupation in 1975, all individuals were classified into groups with
      regard to psychosocial work-environment factors in accordance with a job-exposure
      matrix. Follow-up for alcoholism diagnoses from inpatient care registers (1976 to
      1983) was undertaken for each of the groups. A number of potential confounding
      factors were taken into account RESULTS: Low work control and also low job
      demands and low workplace social support were found to be related to later
      alcoholism. On separate analysis, the pattern among blue-collar workers was found
      to be similar to that of the entire population. When the analyses were extended
      to include indicators of risk use of alcohol and other relevant background
      factors, the relative risks decreased, but were still significantly high in the
      cases of low work control and low work social support. A combination of low
      demands and low control, what might be called a "passive" work environment, was
      related to an increased relative risk of psychiatric alcoholism diagnosis after
      controlling for relevant background factors. CONCLUSIONS: Low work control, in
      particular in combination with low work demands, and low work social support are
      related to later alcoholism even after controlling for previously known risk
      factors (including risk use of alcohol). The results suggest that young men may
      respond to an undemanding occupational environment by increasing their alcohol
      consumption.

PMID- 9660324
TI  - Alcohol consumption and breast cancer stage at diagnosis.
AB  - The stage at which breast cancer is diagnosed is an important determinant of
      prognosis. In contrast to the many investigations of the relationship between
      alcohol consumption and the risk of developing breast cancer, few have examined
      how alcohol consumption may affect the stage of this cancer at diagnosis. This
      article examines the relationship between alcohol intake and breast cancer stage
      and assesses consumption in relation to the volume of drinks consumed per week
      and the patterns of consumption 1 year prior to the breast cancer diagnosis. A
      total of 1191 women, aged 40 to 84 years, with newly diagnosed breast cancer were
      identified through the population-based Metropolitan Detroit Cancer Surveillance
      System, a participant of the Surveillance, Epidemiology, and End Results Program
      of the National Cancer Institute. Of these, 1011 (85%) were interviewed 2 to 4
      months following diagnosis. The analyses for this article were limited to 920
      cases with local and regional stage disease. The bivariate analysis showed that
      frequent drinkers were more likely than abstainers or infrequent drinkers to
      present with regional disease. Logistic regression showed that frequent drinkers
      were 1.45 times more likely than infrequent drinkers to be diagnosed with later
      stage breast cancer (95% CI: 1.01-2.10; p = 05). The association between alcohol
      consumption and disease stage may be due to the relationship between heavy
      consumption and other unhealthy behaviors. In addition, women who drink more
      frequently may have less awareness of and access to cancer screening services.
      Heavy exposure to alcohol may also contribute to accelerated tumor growth once
      breast cancer is present.

PMID- 9660325
TI  - Prevalence of alcohol dependence and abuse in general practice.
AB  - The aim of this study is to deliver representative epidemiological data about the
      prevalence of alcohol abuse and dependence in general practices in an urban area.
      In 12 general practices at Luebeck, a Northern German city with 220,000
      inhabitants, a total of 929 patients (aged between 14 and 75 years) were screened
      using the CAGE and the Short Michigan Alcoholism Screening Test. If one of these
      screening questionnaires or the General Practitioners' assessment of the patient
      indicated an alcohol problem, the patient underwent a standardized diagnostic
      interview using the alcohol section of the Schedules for Clinical Assessment in
      Neuropsychiatry. The prevalence rates according to ICD-10 or DSM-III-R were 3.5%
      for alcohol abuse and 7.2% for alcohol dependence, the sex ratio was 1:2.8
      (female:male). These results are compared with previous findings, and general
      epidemiological implications of this study are discussed.

PMID- 9660326
TI  - Influence of age and body mass index on gamma-glutamyltransferase activity: a 15
      year follow-up evaluation in a community sample.
AB  - Most clinicians and researchers view serum gamma-glutamyltransferase (GGT)
      activity as a measure that can be interpreted equally in patients regardless of
      their demography. The present study evaluates the concurrent influence of age and
      body mass index (BMI) on GGT in a sample of 133 high functioning young men, with
      detailed assessment of the pattern of alcohol use at ages 20 [time 1 (T1)], 30
      [time 2 (T2)], and 35 [time 3 (T3)]. GGT increased between T1 and T2 (15.4 +/-
      9.65 units/liter vs. 20.1 +/- 12.07 units/liter, t = 4.17, p < 0.001), and
      between T2 and T3 (20.1 +/- 12.07 units/liter vs. 27.3 +/- 24.69 units/liter, t =
      4.11, p < 0.001). Controlling for drinking quantity and frequency did not change
      the finding. The relationship between GGT and BMI was estimated after splitting
      the sample into normal (BMI < or = 25 kg/m2) and overweight (BMI > 25 kg/m2)
      subjects. The correlation between GGT and BMI in normal weight men at T1 was r =
      0.15, p = 0.09, at T2 r = 0.00, p = 0.96, and at T3 r = 0.09, p = 0.09. In
      overweight subjects, correlation at T1 was r = 0.40, p = 0.20, at T2 r = 0.36, p
      < 0.05, and at T3 r = 0.44, p < 0.001. Controlling for the effect of alcohol
      consumption and/or age did not alter these conclusions. Testing for the
      interaction of age, BMI, and alcohol consumption did not yield relevant results.
      We concluded that GGT is positively related to age in the 20s to late 30s and to
      BMI in overweight subjects; both relationships of age and BMI were independent of
      alcohol consumption. The interpretation of GGT should take age and BMI into
      account when suspecting subclinical alcohol problems in young men.

PMID- 9660327
TI  - Effects of ethanol on temporal recovery of auditory-evoked potentials in
      individuals at risk for alcoholism.
AB  - The present investigation examined the effects of placebo (P), low dose (LD), and
      high dose (HD) ethanol on auditory event-related potential (AEP) recovery
      functions in a group of males at high risk to develop alcoholism (HR; n = 23,
      mean = 22.3 years) and a low risk (LR; n = 27, mean = 23.0 years) control group.
      Condition order was randomized, with one condition (P, LD, or HD) per day and a
      minimum 1-day interval between conditions. For each subject, both blood alcohol
      levels (BALs) measured via breathalyzer, and event-related potentials recorded
      with the entire 10/20 International System, were assessed prior to and at mean
      intervals of 20, 60, 90, and 130 min after P, LD, or HD administration. A series
      of binaural auditory stimuli with randomly interposed interstimulus intervals of
      0.5, 1.0, and 10.0 sec were used to elicit the N100 and P200 components of the
      AEP. Between-groups comparisons indicated that ethanol elicited risk group
      differences in recovery functions not present at baseline. The differences were
      manifested in the HR group as larger decrements in P200 amplitude during the
      ascending blood alcohol curve (acute sensitivity) and more rapid returns of both
      N100 and P200 to baseline levels during the descending blood alcohol curve (acute
      tolerance). These findings support Newlin and Thomson's (1990) Differentiator
      Model, suggesting that LR and HR individuals are differentially sensitive to the
      effects of ethanol.

PMID- 9660328
TI  - Neurocognitive deficits in alcoholics and social drinkers: a continuum?
AB  - Our research program has investigated neurocognitive deficits in sober alcoholics
      for several decades. We have shown that both male and female adult alcoholics-
      compared with peer nonalcoholic controls--have deficits on tests of learning,
      memory, abstracting, problem-solving, perceptual analysis and synthesis, speed of
      information processing, and efficiency. The deficits are equivalent to those
      found in patients with known brain dysfunction of a mild to moderate nature.
      Attempts to identify factors other than alcoholism to account for these
      differences have been unsuccessful. The deficits appear to remit slowly over 4 to
      5 years. Relapse of recovering alcoholics is predicted by behavioral (e.g.,
      depressive symptoms and neurocognitive performance) and biological measures
      (e.g., event-related potentials) obtained at the end of treatment. Results of
      recent studies support the hypothesis of a continuum of neurocognitive deficits
      ranging from the severe deficits found in Korsakoff patients to moderate deficits
      found in alcoholics and moderate to mild deficits in heavy social drinkers (more
      than 21 drinks/week). Individual differences in the presence and magnitude of
      neurocognitive deficits in social drinkers and alcoholics are hypothesized to be
      due, in part, to individual differences in vulnerability of the brain to alcohol
      or its metabolites' toxic effects.

PMID- 9660329
TI  - Autocrine transforming growth factor beta stimulation of extracellular matrix
      production by fibroblasts from fibrotic human gingiva.
AB  - Hereditary gingival fibromatosis (HGF) is a fibrotic enlargement of the gingiva.
      HGF gingiva contains large amounts of collagen and other extracellular matrix
      (ECM) molecules. In vitro, HGF fibroblasts produce greater amounts of the ECM
      components fibronectin (FN) and type 1 collagen than normal human gingival (GN)
      fibroblasts. Transforming growth factor beta (TGF beta) is a cytokine important
      in regulating tissue repair and regeneration after injury, and stimulating
      fibroblast proliferation and the production of FN and collagens. The objective of
      this study was to determine whether HGF fibroblasts produce TGF beta and, with
      the use of neutralizing antibodies to TGF beta isoforms, if their increased
      expression of FN and type 1 collagen is under autocrine TGF beta control. The HGF
      strains produced greater amounts of TGF beta1 and TGF beta2 (P < or = 0.003) as
      well as FN (P < or = 0.04) and type 1 collagen (P < or = 0.03) (measured by
      specific ELISA) than the GN strains. Treatment of HGF fibroblasts with anti-TGF
      beta1, beta2, or beta3, as well as a combination of all 3 antibodies, decreased
      their FN production by up to 60% (P < or = 0.04), and was able to decrease FN
      production by HGF fibroblasts to the levels of the GN fibroblasts. When used
      alone, the neutralizing antibodies decreased type 1 collagen production by the
      HGF fibroblasts by up to 40% (P = 0.014), and treatment with all 3 antibodies
      caused decreases of up to 55% (P = 0.0005). The results suggest that autocrine
      stimulation by the increased amounts of TGF beta isoforms made by HGF fibroblasts
      contributes to their increased production of FN and type 1 collagen.

PMID- 9660330
TI  - Irritant contact stomatitis: a review of the condition.
AB  - Several different types of interactions are possible between a chemical, a
      mixture of chemicals, and associated extrinsic factors (i.e., mechanical
      irritation) in the oral mucosa. These interactions can be broadly classified as
      irritative or allergenic in nature. In each case, the pathology usually includes
      mucosal inflammation. The information compiled and reviewed in this article
      suggests that, given the broad definition of surface lesions/mucosal
      abnormalities, there may be a continuum of irritation that can be termed
      "irritant contact stomatitis." This may be due to the fact that the mouth is
      lined with highly vascular mucosa that turns over rapidly compared to the skin,
      and may or may not be covered by keratin. Some regions in the mouth are uniquely
      sensitive to irritants because they can penetrate through the tissue easily. Key
      factors involved in the potential development of irritation are: inherent
      irritation potential of the agent, amount of exposure (concentration, duration,
      and frequency), ability to penetrate the tissue, and inherent reactivity of the
      subject as well as other extrinsic factors. Irritation leading to oral mucosal
      alterations is a common occurrence caused by a wide variety of exposures and
      insults to the oral cavity. Various irritants such as foods, chemicals, friction,
      thermal/mechanical injury, metals, spices, and oral care products have been
      documented to cause irritant reactions in susceptible individuals, particularly
      if used under exaggerated exposure conditions. It is important to note that most
      irritation in the oral cavity tends to reverse quickly when the causative agent
      is removed. Oral irritation is a commonly occurring phenomenon. Thus, it is
      important that the clinician be aware of the clinical manifestations and etiology
      of the condition.

PMID- 9660331
TI  - Clinical comparison of bioabsorbable barriers with non-resorbable barriers in
      guided tissue regeneration in the treatment of human intrabony defects.
AB  - The purpose of the study was to compare the effects of guided tissue regeneration
      (GTR) with expanded polytetrafluoroethylene (ePTFE) non-resorbable barriers and
      polylactic acid bioabsorbable barriers in humans with intrabony defects due to
      periodontitis. Ten patients presented with 2 intrabony defects each.
      Mucoperiosteal flaps were performed. One of the defects was randomly assigned for
      placement of the ePTFE barrier over the roots and alveolar bone and the other
      defect with placement of the polylactic acid barrier. A minimum of 9 months after
      barrier placement, surgical reentry was performed. The data were evaluated by the
      Wilcoxon matched-pairs signed-ranks test and the Fisher exact test. Treatment
      with both types of barriers produced significant changes from baseline for all
      parameters, except in the ePTFE group for the amount of bony crest resorption (P
      = 0.055) and in the polylactic acid group for increased recession (P = 0.109).
      The results showed no significant differences between the barriers for any
      parameters: probing depth reduction (polylactic acid 2.60 +/- 1.90, ePTFE 2.80 +/
      1.40; P = 1.000); attachment gain (polylactic acid 1.40 +/- 1.43, ePTFE 1.90 +/-
      1.29; P = 0.336); increased recession (polylactic acid 0.80 +/- 1.40, ePTFE 1.10
      +/- 0.99; P = 0.531); amount of vertical bone fill (polylactic acid 1.60 +/-
      1.84, ePTFE 2.00 +/- 2.49; P = 0.984); bony crest resorption (polylactic acid 
      1.30 +/- 1.06, ePTFE -1.30 +/- 1.63; P = 1.000); depth of bony defect reduction
      (polylactic acid 2.90 +/- 1.20, ePTFE 3.30 +/- 1.70; P = 0.750); width of bony
      defect reduction (polylactic acid 2.20 +/- 1.23, ePTFE 2.20 +/- 1.23; P = 0.875);
      or volumetric changes (polylactic acid 33.50 +/- 19.70 microl, ePTFE 34.00 +/-
      18.40 microl; P = 0.750).

PMID- 9660332
TI  - Fibroblast heterogeneity of signal transduction mechanisms to complement-C1q.
      Analyses of calcium mobilization, inositol phosphate accumulation, and protein
      kinases-C redistribution.
AB  - Fibroblasts of healthy and granulation gingiva are phenotypically heterogeneous
      with regard to binding C1q collagen-like (cC1qR) or C1q globular-heads (gC1qR)
      regions, respectively. Here, isolated fibroblast subsets, expressing either the
      cC1qR or the gC1qR phenotype, were stimulated with C1q, and assessed for changes
      in cytosolic free calcium [Ca2+]i, accumulation of inositol trisphosphate (IP3),
      and redistribution of Ca2+-dependent protein kinases-C (cPKCs) from cytosol to
      membranes. Changes in [Ca2+]i were determined using Indo-1 fluorescence in
      combination with adhering cell analysis and sorting (ACAS) cytometry.
      Accumulation of IP3 was quantified using a competitive radioreceptor binding
      assay. Redistribution of cPKCs was evaluated by immunoblotting with antibodies to
      PKCalpha/betaI-betaII/gamma. Subsets manifested different fluctuations in [Ca2+]i
      levels 20 seconds after C1q-stimulation in the presence of millimolar
      concentrations of external calcium. Whereas cC1qR fibroblasts responded with a
      38% over baseline [Ca2+]i increase which was sustained for 20 to 30 minutes,
      gC1qR fibroblasts responded with a higher (264% over baseline) and more rapid (2
      to 3 minutes) transient. Likewise, subsets exhibited different kinetics of IP3
      accumulation. Whereas cC1qR fibroblasts responded with an IP3 increase of 32 +/-
      3 pmol/10(4) cells over baseline after 5 seconds stimulation, gC1qR fibroblasts
      responded after 15 to 20 seconds with a lower increase (13 +/- 0.8 IP3 pmol/10(4)
      cells over baseline). Subsets differed in cPKCs redistribution which peaked in
      gC1qR-membranes 30 seconds after stimulation and remained sustained between 10
      and 30 minutes. No cPKC redistribution was detectable in stimulated cC1qR-cells.
      We conclude that fibroblasts are heterogeneous in phosphoinositide-Ca2+ signaling
      and cPKC redistribution to C1q, and suggest that these differences may affect
      activities of normal and granulation gingiva.

PMID- 9660333
TI  - Equivalence in periodontal trials: a description for the clinician.
AB  - There has been a tendency by clinicians in periodontal research to confuse lack
      of significance in a clinical trial designed for superiority for equivalence
      between the treatment arms. This paper is intended to define for the clinician
      what equivalency means in statistical terms. To demonstrate equivalence, the
      hypotheses and analysis specific to equivalence must be carried out; the
      information cannot be extracted directly from trials designed with superiority
      hypotheses and analysis. Further, acceptable mean differences in equivalency
      trials should be determined based not only on statistical considerations, but
      also on the clinical relevance of the proposed differences. The relationship
      between superiority and equivalency design and analysis is discussed and an
      example using a hypothetical clinical study is given.

PMID- 9660334
TI  - Multi-center clinical evaluation of combination anorganic bovine-derived
      hydroxyapatite matrix (ABM)/cell binding peptide (P-15) as a bone replacement
      graft material in human periodontal osseous defects. 6-month results.
AB  - A synthetic cell-binding peptide (P-15) combined with anorganic bovine-derived
      hydroxyapatite bone matrix (ABM) was compared to demineralized freeze-dried bone
      allograft (DFDBA) and open flap debridement (DEBR) in human periodontal osseous
      defects in a controlled, monitored, multi-center trial. Following appropriate
      initial preparation procedures, flap surgery with defect and root debridement was
      performed. Three osseous defects per patient were treated randomly with one of
      three procedures after surgical preparation. Appropriate periodontal maintenance
      schedules were followed, and at 6 to 7 months re-entry flap surgery was performed
      for documentation and finalization of treatment. Analysis of variation (ANOVA)
      and t test analyses of patient mean values from 31 patients revealed that the
      combination ABM/P-15 grafts demonstrated significantly better mean defect fill of
      2.8 +/- 1.2 mm (72.3%) versus a mean defect fill of 2.0 +/- 1.4 mm (51.4%) for
      defects treated with DFDBA (P <0.05) and a mean defect fill of 1.5 +/- 1.3 mm
      (40.3%) (P <0.05) for defects treated with DEBR. Other hard tissue findings
      showed similar clinically superior results with the use of ABM/P-15. Relative
      defect fill results showed 87% positive (50% to 100% defect fill) responses with
      ABM/P-15, 58% positive responses with DFDBA, and 41% positive responses with
      DEBR. There were 8 to 9 times more failures (minimal response) with DFDBA and
      DEBR (26% to 29% frequency) than with ABM/P-15. Soft tissue findings showed no
      significant differences among treatments except for greater clinical attachment
      level gain with ABM/P-15 compared to DEBR. These results suggest that the use of
      the P-15 synthetic cell-binding peptide combined with ABM yields better clinical
      results than either DFDBA or DEBR. Further studies are needed to determine the
      relative roles of the ABM and/or the P-15 in these improved results.

PMID- 9660335
TI  - Subgingival microflora associated with nifedipine-induced gingival overgrowth.
AB  - The purpose of this study was to examine the composition of subgingival plaque of
      140 periodontal lesions in 35 patients with cardiovascular disorders who were
      administered nifedipine and manifested nifedipine-induced gingival overgrowth
      (GO). Age was inversely associated with the GO. Plaque index and bleeding index
      showed a significant association with GO, while nifedipine dosage and duration of
      nifedipine therapy were not found to be significant predictors of GO. The
      gingival inflammation as expressed in the logistic regression model by the
      interaction term color x tone was found to be significantly associated with the
      GO. Statistically significant differences between the groups of comparable
      probing depth and different degrees of GO were detected for Propionibacterium
      acnes, Capnocytophaga gingivalis, Capnocytophaga ochracea, Capnocytophaga
      sputigena, Bacteroides gracilis, Fusobacterium mortiferum, Fusobacterium
      nucleatum, Fusobacterium varium and Selenomonas sputigena in deep and enlarged
      lesions. Significantly more frequently isolated were the bacterial species
      Eubacterium alactolyticum, Campylobacter concisus, C. gingivalis, C. ochracea, C.
      sputigena, F. mortiferum, F. nucleatum, and F. varium from the more enlarged
      lesions (GO >3).

PMID- 9660336
TI  - Induction of COX-2 expression by mechanical tension force in human periodontal
      ligament cells.
AB  - Occlusal trauma is caused by excessive occlusal forces and is associated with
      alveolar bone loss. In the periodontal ligament (PDL), which primarily receives
      the occlusal force, there is increased prostaglandin E (PGE2) synthesis in
      response to mechanical stress, and many studies have shown that PGE2 is involved
      in the pathogenesis of periodontal diseases. Recently, two isozymes of
      cyclooxygenase, COX-1 and COX-2, which are key enzymes in prostaglandin (PG)
      biosynthesis, were identified and COX-2 was induced following the activation of
      cells by a variety of proinflammatory agents. However, the biosynthetic pathway
      of mechanical stress-dependent PGE2 from PDL cells has not been well understood.
      When cyclic tension force was applied to human PDL cells (18% increase in surface
      area), PGE2 release to the culture medium increased in a time-dependent manner.
      As analyzed by semi-quantitative PCR, COX-2 mRNAs, while hardly detectable in
      controls, increased dramatically on day 3 and 5 in response to tension force. In
      contrast, COX-1 mRNAs detected in controls were not affected by tension force. By
      immunocytochemical staining, COX-2 protein was significantly increased by tension
      force around the unstained cell nucleus in a time-dependent manner. When NS-398,
      a selective COX-2 inhibitor, was added to the medium, PGE2 synthesis increased by
      tension force was completely inhibited. These results indicate that tension force
      induces COX-2 in human PDL cells and that this induction is responsible for the
      augmentation of PGE2 production stimulated by tension force. Since selective COX
      2 inhibitors have less adverse effects compared with those of non-steroidal anti
      inflammatory drugs, they may be of therapeutic benefit for treatment of
      periodontal disease accompanying traumatic occlusion.

PMID- 9660337
TI  - Analysis of desquamative gingivitis using direct immunofluorescence in
      conjunction with histology.
AB  - Chronic desquamative gingivitis (DG) is a common condition often first recognized
      by periodontists. DG is characterized clinically by erythema with epithelial
      desquamation, ulceration, and/or the presence of vesiculobullous lesions of the
      free and attached gingiva. However, DG is actually a clinical manifestation of
      several different disease processes, particularly lichen planus and benign mucous
      membrane pemphigoid. Correct diagnosis in DG is critical since proper treatment
      and follow-up will depend on which disease is involved. However, the diseases
      that cause DG frequently present diagnostic problems because their lesions often
      resemble each other clinically and routine histological examination sometimes
      cannot differentiate between them. Thus, immunohistology, particularly
      immunofluorescence, is increasingly being used with routine histology to more
      accurately diagnose DG diseases. This article reviews our experience over the
      past 10 years in the diagnosis of 72 cases of DG using direct immunofluorescent
      (DIF) in conjunction with histology and clinical evaluation. Of the 72 DG cases
      in this study, 30 cases were diagnosed as erosive lichen planus or lichenoid
      mucositis; 29 cases were diagnosed as benign mucous membrane pemphigoid; 2 cases
      each of linear IgA disease and pemphigus vulgaris were diagnosed; there was 1
      case of bullous pemphigoid; and 1 suspected case of paraneoplastic pemphigus.
      Even with DIF analysis, 7 cases could not be definitively assigned a particular
      cause. DIF analysis is not only proving very useful for differential diagnosis,
      but also adds insight into possible pathogenic mechanisms of DG.

PMID- 9660338
TI  - Immunization with Porphyromonas gingivalis cysteine protease: effects on
      experimental gingivitis and ligature-induced periodontitis in Macaca
      fascicularis.
AB  - Targeting bacterial virulence factors such as proteases for immunization may hold
      the key to limiting or preventing loss of attachment and alveolar bone in
      periodontal disease. This study examined the clinical, microbiological, and
      immununological responses following active immunization with a purified
      Porphyromonas gingivalis cysteine protease (porphypain-2) in the nonhuman primate
      (Nhp) Macaca fascicularis. One group of Nhp was immunized with porphypain-2
      antigen while control Nhp received placebo injections. All Nhp were subjected to
      experimental gingivitis followed by ligature-induced periodontitis in a split
      mouth design. An enzyme-linked immunosorbent assay demonstrated that immunization
      elicited a significantly elevated and specific IgG antibody response to both
      whole cell P. gingivalis (36-fold) and to porphypain-2 (194-fold). Checkerboard
      hybridization DNA analysis of subgingival plaque from ligated sextants
      demonstrated that 25% more Gram-negative anaerobic species became significantly
      elevated from baseline and at earlier timepoints in the control group than in the
      immununized group. Immunization with this protease did not suppress the emergence
      of P. gingivalis. Clinical indices showed few changes related to immunization.
      Alveolar bone density changes demonstrated a highly significant loss in ligated
      sextants compared to non-ligated sextants within the control group (P < 0.001),
      and a smaller but significant difference within the immunized group (P = 0.043).
      Comparison of ligated sextants only demonstrated more bone loss in the control
      group versus the immunized group (-13.07+/-9.51 versus -9.41+/-6.18; computer
      assisted densitometric image analysis units +/- SD); the difference approached,
      but did not reach, significance. The results suggest that porphypain-2 may
      contribute to the pathogenic potential of the subgingival plaque microbiota in
      the Nhp model of ligature-induced periodontitis, and that active immunization
      with porphypain-2 appeared capable of altering this pathogenic response.

PMID- 9660339
TI  - Comparison of bioactive glass synthetic bone graft particles and open debridement
      in the treatment of human periodontal defects. A clinical study.
AB  - The purpose of this study was to compare the repair response of bioactive glass
      synthetic bone graft particles and open debridement in the treatment of human
      periodontal osseous defects. Fifty-nine defects in 16 healthy adults were
      selected. Each patient had at least 2 sites with attachment loss of at least 6 mm
      with clinical and radiographic evidence of intrabony or furcation defects. One to
      3 months after cause-related therapy (oral hygiene instructions, scaling and root
      planing), the following measurements were recorded prior to surgery: probing
      depths, clinical attachment level, and gingival recession. Each defect was
      surgically exposed and measurements made of the alveolar crest height and base of
      osseous defect. The test defects were implanted with bioactive glass. The other
      sites served as unimplanted controls. Flaps were sutured at or close to the
      presurgical level. Radiographs and soft tissue presurgical measurements were
      repeated at 6, 9, and 12 months. At 12 months all sites were surgically re
      entered to record osseous measurements. At the 12-month evaluation, significantly
      greater mean probing depth reduction was noted in the bioactive glass group
      compared to the controls (4.26 mm versus 3.44 mm; P = 0.028). Clinical attachment
      level gain was significantly improved (P = 0.0004) in the bioactive glass sites
      (2.96 mm) compared to the control sites (1.54 mm). There was significantly less
      gingival recession in the bioactive glass sites (1.29 mm) compared to the control
      sites (1.87 mm). Defect fill was significantly greater in the bioactive glass
      sites (3.28 mm) compared to the control sites (1.45 mm). Defect depth reduction
      was significantly greater in the bioactive glass sites (4.36 mm) compared to the
      control sites (3.15 mm). In conclusion, bioactive glass showed significant
      improvement in clinical parameters compared to open flap debridement.

PMID- 9660341
TI  - Treatment of a previously placed autogenous masticatory mucosa graft (free
      gingival graft). A case report.
AB  - The autogenous masticatory mucosa graft (free gingival graft) has been used to
      treat various mucogingival conditions. Unfortunately, the esthetics of the
      procedure are often less than ideal. This case report examines the treatment of
      an unesthetic free gingival graft. The goal was to create a result so that it was
      impossible to tell there had ever been a free gingival graft or any surgery
      performed to correct a problem. To achieve this goal, 3 periodontal plastic
      surgical procedures were utilized and a crown was placed. This integration of
      multiple surgical procedures and prosthetics produced an outstanding result.

PMID- 9660340
TI  - Rapid progression of bone loss in HIV-associated necrotizing ulcerative
      stomatitis.
AB  - This report describes a case of rapidly progressive periodontal tissue breakdown
      and bone loss in an HIV-infected markedly immunosuppressed homosexual male.
      Within 6 months of initial presentation with a necrotizing ulcerative gingivitis,
      the lesion extended to a necrotizing ulcerative stomatitis involving the
      surrounding periodontium and palatal mucosa. With only partial compliance to
      local debridement, chlorhexidine oral rinses, and systemic metronidazole therapy,
      alveolar bone loss resulted in tooth mobility necessitating extraction of 2
      involved teeth. This case illustrates the continuum of necrotizing ulcerative
      infections of the periodontium in the severely immunosuppressed patient. The
      implications of these oral manifestations of HIV infection are discussed.

PMID- 9660342
TI  - Management of gingival vitiligo with the use of a tattoo technique.
AB  - The purpose of this report is to describe the management of gingival vitiligo in
      a black female. This patient was referred by her psychiatrist to the Mount Sinai
      Hospital Dental Department (Toronto) for assessment of progressive loss in
      gingival pigmentation. According to her psychiatrist this loss of pigmentation,
      which the patient indicated may be considered in Africa as a hallmark of HIV
      infection, was a significant exogenous factor in relation to the patient's
      ongoing clinical depression. After obtaining informed consent, a modification of
      a tattooing method used for skin was applied to the patient's attached gingival
      tissues. Test sites were tattooed prior to performing full gingival tattooing
      under local anaesthesia. The results demonstrate that it was possible to restore
      this patient's gingival pigmentation in a highly esthetically acceptable manner.
      The resulting coloration was reminiscent of the patient's natural pigmentation
      that had been lost ostensibly because of her systemic disorder. Our findings also
      showed that the artificial pigmentation established via the tattoo method was
      stable 4 months postoperatively and continues to be stable, as expected. A
      profound improvement in the patient's mood was noted.

PMID- 9660344
TI  - AIDS vaccine moves into phase 3 trials.

PMID- 9660343
TI  - Reduction of cyclosporine-induced gingival overgrowth following a change to
      tacrolimus. A case history involving a liver transplant patient.
AB  - During immunosuppression with cyclosporine, gingival overgrowth, a minor
      secondary effect, may appear in the first weeks of treatment. In certain cases it
      may affect the function and/or esthetic appearance in a manner intolerable to the
      patient. A new immunnosuppressive molecule, tacrolimus, presently used as a
      treatment of second choice to control acute corticoresistant rejection, may bring
      oral comfort to these patients, since it reduces gingival overgrowth to
      negligible levels.

PMID- 9660345
TI  - Mixed response to new PSA screening study.

PMID- 9660346
TI  - Urologists present positive evidence for early test.

PMID- 9660347
TI  - SEC going after insider trading based on medical research results. Securities
      Exchange Commission.

PMID- 9660348
TI  - From the Food and Drug Administration.

PMID- 9660349
TI  - From the Centers for Disease Control and Prevention. Silicosis deaths among young
      adults--United States, 1968-1994.

PMID- 9660350
TI  - From the Centers for Disease Control and Prevention. Population-based survey for
      drug resistance of tuberculosis--Mexico, 1997.

PMID- 9660351
TI  - Prevention and treatment of pediatric HIV infection.

PMID- 9660352
TI  - Simultaneous infection with HIV and hepatitis C virus following occupational
      conjunctival blood exposure.

PMID- 9660353
TI  - How many pills do patients with HIV infection take?

PMID- 9660354
TI  - Sexual behavior of HIV-infected women reporting recent sexual contact with women.

PMID- 9660355
TI  - Cost-effectiveness of zidovudine to prevent mother-to-child transmission of HIV
      in sub-Saharan Africa.

PMID- 9660356
TI  - Hazards of glass capillary tubes to health care workers.

PMID- 9660357
TI  - Serologic evidence for mother-to-child transmission of Kaposi sarcoma-associated
      herpesvirus infection.

PMID- 9660358
TI  - Tobacco smoke and atherosclerosis progression.

PMID- 9660359
TI  - Tobacco smoke and atherosclerosis progression.

PMID- 9660360
TI  - Tobacco smoke and atherosclerosis progression.

PMID- 9660361
TI  - Simultaneous vs sequential initiation of therapy with indinavir, zidovudine, and
      lamivudine for HIV-1 infection: 100-week follow-up.
AB  - CONTEXT: Combination antiretroviral therapy can markedly suppress human
      immunodeficiency virus (HIV) replication but the duration of HIV suppression
      varies among patients. OBJECTIVE: To compare the antiretroviral effect of a 3
      drug regimen started simultaneously or sequentially in patients with HIV
      infection. DESIGN: A multicenter, randomized, double-blind study, modified after
      at least 24 weeks of blinded therapy to provide open-label 3-drug therapy with
      follow-up through 100 weeks. SETTING: Four clinical research units PATIENTS:
      Ninety-seven patients with HIV infection who had taken zidovudine for at least 6
      months with serum HIV RNA level of at least 20000 copies/mL and CD4 cell count of
      0.05 to 0.40 x 10(9)/L. INTERVENTIONS: Patients were initially randomized to
      receive 1 of 3 antiretroviral regimens: indinavir, 800 mg every 8 hours;
      zidovudine, 200 mg every 8 hours and lamivudine, 150 mg every 12 hours; or all 3
      drugs. After at least 24 weeks of blinded therapy, all patients received open
      label 3-drug therapy. MAIN OUTCOME MEASURES: Antiretroviral activity was assessed
      by changes in HIV RNA level and CD4 cell count from baseline. Data through 100
      weeks were summarized. RESULTS: Simultaneous initiation of indinavir, zidovudine,
      and lamivudine suppressed HIV RNA in 78% (25/32) of contributing patients to less
      than 500 copies/mL and increased CD4 cell count to a median of 0.209 x 10(9)/L
      above baseline at 100 weeks. When these 3 drugs were initiated sequentially, only
      30% to 45% of contributing patients (10 of 33 in the zidovudine-lamivudine group
      and 13 of 29 in the indinavir group, respectively) had a sustained reduction in
      HIV RNA to less than 500 copies/mL, and median CD4 cell count increased to 0.101
      to 0.163 x 10(9)/L above baseline at 100 weeks. CONCLUSIONS: A 3-drug combination
      of indinavir, zidovudine, and lamivudine started simultaneously has durable
      antiretroviral activity for at least 2 years. Sequential initiation of the same 3
      drugs is much less effective.

PMID- 9660362
TI  - New testing strategy to detect early HIV-1 infection for use in incidence
      estimates and for clinical and prevention purposes.
AB  - CONTEXT: Differentiating individuals with early human immunodeficiency virus 1
      (HIV-1) infection from those infected for longer periods is difficult but
      important for estimating HIV incidence and for purposes of clinical care and
      prevention. OBJECTIVE: To develop and validate a serologic testing algorithm in
      which HIV-1-positive persons with reactive test results on a sensitive HIV-1
      enzyme immunoassay (EIA) but nonreactive results on a less sensitive (LS) EIA are
      identified as having early infection. DESIGN: Diagnostic test and testing
      strategy development, validation, and application. Specimens were tested with
      both a sensitive HIV-1 EIA (3A11 assay) and a less sensitive modification of the
      same EIA (3A11-LS assay). SETTINGS AND PARTICIPANTS: For assay development: 104
      persons seroconverting to HIV-1 comprising 38 plasma donors, 18 patients of a
      sexually transmitted disease clinic in Trinidad, and 48 participants in the San
      Francisco Men's Health Study (SFMHS); 268 men without the acquired
      immunodeficiency syndrome (AIDS) in the SFMHS who had been infected for at least
      2.5 years; and 207 persons with clinical AIDS; for testing strategy validation:
      488 men in the SFMHS from 1985 through 1990 and 1275449 repeat blood donors at 3
      American Red Cross blood centers from 1993 through 1995; and for HIV-1 incidence
      estimates: 2717910 first-time blood donors. We retrospectively identified persons
      eligible for a study of early infection. MAIN OUTCOME MEASURE: Ability to
      identify early HIV infection. RESULTS: Estimated mean time from being 3A11
      reactive/3A11-LS nonreactive to being 3A11 reactive/3A11-LS reactive was 129 days
      (95% confidence interval [CI], 109-149 days) [corrected]. Our testing strategy
      accurately diagnosed 95% of persons with early infection; however, 0.4% (1/268)
      of men with established infection and 2% (5/207) of persons with late-stage AIDS
      were misdiagnosed as having early HIV-1 infection. Average yearly incidence
      estimates in SFMHS subjects were 1.5% per year vs observed average incidence of
      1.4 per 100 person-years. Incidence in repeat blood donors using the
      sensitive/less sensitive assay testing strategy was 2.95 per 100000 per year (95%
      CI, 1.14-6.53/100000) vs observed incidence of 2.60 per 100000 person-years (95%
      CI, 1.49-4.21/100000). Overall incidence in first-time blood donors was 7.18 per
      100000 per year (95% CI, 4.51-11.20/100000) and did not change statistically
      significantly between 1993 and 1996. Use of the sensitive/less sensitive testing
      strategy alone would have identified all 17 persons with antibodies to HIV-1
      eligible for a study of early HIV-1 infection and would have increased
      enrollment. CONCLUSIONS: The sensitive/less sensitive testing strategy provides
      accurate diagnosis of early HIV-1 infection, provides accurate estimates of HIV-1
      incidence, can facilitate clinical studies of early HIV-1 infection, and provides
      information on HIV-1 infection duration for care planning.

PMID- 9660363
TI  - HIV prevalence, risk, and partner serodiscordance among pregnant women in
      Bangkok. Bangkok Collaborative Perinatal HIV Transmission Study Group.
AB  - CONTEXT: Most prior studies of the human immunodeficiency virus (HIV) epidemic in
      Thailand have focused on commercial sex encounters; however, because the epidemic
      increasingly concerns stable heterosexual relationships, determining risk factors
      for this form of transmission is warranted. OBJECTIVES: To determine temporal
      trends in HIV prevalence, risk factors for HIV seropositivity, and rates of
      partner serodiscordance for pregnant women in Bangkok, Thailand. DESIGN:
      Retrospective review of hospital antenatal clinic HIV test results from 1991
      through 1996. Baseline demographic and behavioral risk factors for HIV were
      assessed for subjects enrolled from November 1992 through March 1994. SETTING:
      Two Bangkok hospitals with routine antenatal clinic HIV counseling and testing.
      PARTICIPANTS: The HIV-positive pregnant women enrolled in a perinatal HIV
      transmission study and their partners and HIV-negative pregnant controls.
      RESULTS: From 1991 through 1996, antenatal clinic HIV seroprevalence increased
      from 1.0% to 2.3%. On multivariate analysis of data from 342 HIV-positive and 344
      HIV-negative pregnant women, more than 1 lifetime sex partner, history of a
      sexually transmitted disease, and a high-risk sex partner were the most important
      factors for seropositivity (all P<.001). Twenty-six percent of partners of HIV
      positive women were HIV negative. Women reporting more than 1 lifetime sex
      partner were more likely to have an HIV-negative partner than women reporting
      only 1 (45% vs 8%; relative risk, 5.5; 95% confidence interval, 3.2-9.5; P<.001);
      women reporting no high-risk behaviors were less likely to have an HIV-negative
      partner (10% vs 44%; relative risk, 0.2; 95% confidence interval, 0.1-0.4;
      P<.001). CONCLUSIONS: Prevalence of HIV in pregnant women has increased steadily
      in Bangkok from 1991 through 1996. Sex with current partners was the only
      identified risk exposure for about half (52%) of the HIV-positive women. Although
      few HIV-positive pregnant women reported high-risk behaviors, more than 1
      lifetime partner and a partner with high-risk behavior were strong risk factors
      for seropositivity. Together with the unexpected finding that one fourth of
      partners of seropositive pregnant women were seronegative, these data emphasize
      that women in the general population are at risk for HIV because of the risk
      behavior of both current and previous partners.

PMID- 9660364
TI  - Perinatal HIV-1 transmission: interaction between zidovudine prophylaxis and mode
      of delivery in the French Perinatal Cohort.
AB  - CONTEXT: It is unclear whether elective cesarean delivery may have a protective
      effect against the transmission of human immunodeficiency virus 1 (HIV-1).
      OBJECTIVE: To investigate whether mode of delivery has an impact on perinatal HIV
      1 transmission in the presence of zidovudine prophylaxis. DESIGN: A prospective
      cohort study. SETTING: The 85 perinatal centers in the French Perinatal Cohort,
      from 1985 to 1996. PATIENTS: A total of 2834 singleton children born to mothers
      with HIV-1 infection. MAIN OUTCOME MEASURE: Human immunodeficiency virus 1
      infection of the infant. RESULTS: No zidovudine was used in 1917 pregnancies and
      zidovudine prophylaxis was used in 902 pregnancies. Cesarean deliveries were
      performed in 10.9% on an emergent basis and in 8.3% electively, prior to labor or
      membrane rupture. In 1917 mothers who did not receive zidovudine, of 1877 with
      information on mode of delivery, 17.2% transmitted HIV-1 to their child. Risk
      factors statistically significantly associated with transmission were maternal
      p24 antigenemia, cervicovaginal infections during pregnancy, amniotic fluid
      color, and rupture of membranes 4 hours or more before delivery. Mode of delivery
      was not related to transmission. In 902 mothers receiving zidovudine,
      transmission was 6.4% in 872 with information on mode of delivery, and elective
      cesarean delivery (n = 133) was associated with a lower transmission rate than
      emergent cesarean or vaginal delivery (0.8%, 11.4%, and 6.6%, respectively;
      P=.002). In a multivariate analysis of all mother-child pairs, including
      obstetrical risk factors, maternal p24 antigenemia, and zidovudine prophylaxis,
      interaction between mode of delivery and zidovudine prophylaxis was significant
      (P=.007). In the multivariate analysis of pregnancies with zidovudine
      prophylaxis, factors related to transmission rate were maternal p24 antigenemia,
      amniotic fluid color, and mode of delivery. Adjusted odds ratios (95% confidence
      intervals) were 1.6 (0.7-3.6) for emergent cesarean delivery and 0.2 (0.0-0.9)
      for elective cesarean delivery (P = .04) in comparison with vaginal delivery.
      CONCLUSIONS: We observed an interaction between zidovudine prophylaxis and
      elective cesarean delivery in decreasing transmission of HIV-1 from mother to
      child. This observation may have clinical implications for prevention.

PMID- 9660365
TI  - Frequent recovery of HIV-1 from genital herpes simplex virus lesions in HIV-1
      infected men.
AB  - CONTEXT: Genital ulcer disease has been epidemiologically linked as a risk factor
      in the transmission of the human immunodeficiency virus 1 (HIV-1). While herpes
      simplex virus 2 (HSV-2) is the most common cause of genital ulcers, no study has
      systematically evaluated the frequency or titer of HIV-1 virus in HSV-2 lesions.
      OBJECTIVE: To compare lesional HIV-1 RNA levels during and after genital HSV-2
      reactivation and to evaluate the frequency, titer, and duration of HIV-1 RNA
      shedding in lesions due to HSV-2. DESIGN: Convenience sample. SETTING: Sexually
      transmitted disease research clinic at the University of Washington, Seattle.
      PATIENTS: Twelve HIV-infected men with a history of symptomatic HSV-2 infection
      who underwent daily sampling of genital lesions for HIV-1 RNA by polymerase chain
      reaction assay and HSV-2 by culture. MAIN OUTCOME MEASURE: Detection of lesional
      HIV RNA and HSV-2. RESULTS: HIV-1 RNA was detected from lesional swabs in 25 of
      26 consecutively studied HSV-2 episodes and on 67% of days in which genital
      lesions were noted. The HIV-1 RNA titers in lesional swabs exceeded 10000
      copies/mL of swab sample in 75% of samples (range, 2.2-3.2 x 10(5) copies/mL of
      swab sample). HIV-1 RNA in genital lesion swabs was seen in persons with high and
      low titers of plasma HIV-1 RNA and was not associated with plasma HIV-1 RNA
      levels. CONCLUSIONS: HIV-1 virions can consistently be detected in genital ulcers
      caused by HSV-2, which suggests that genital herpes infection likely increases
      the efficiency of the sexual transmission of HIV-1.

PMID- 9660366
TI  - Cellular and anatomical reservoirs of HIV-1 in patients receiving potent
      antiretroviral combination therapy.
AB  - The eradication of human immunodeficiency virus 1 (HIV-1) from infected persons
      is the ultimate goal of HIV therapeutic interventions. Great strides have been
      made in developing potent antiretroviral regimens that greatly suppress HIV-1
      replication. Despite these therapeutic advances, major obstacles remain to
      eradicating HIV-1. Reservoirs of HIV-1 have been identified that represent major
      impediments to eradication. Conceptually, there are 2 types of sanctuaries for
      HIV-1, cellular and anatomical. Cellular sanctuaries may include latent CD4+ T
      cells containing integrated HIV-1 provirus; macrophages, which may express HIV-1
      for prolonged periods; and follicular dendritic cells, which may hold infectious
      HIV-1 on their surfaces for indeterminate lengths of time. The key anatomical
      reservoir for HIV-1 appears to be the central nervous system. An understanding of
      the nature of HIV within these reservoirs is critical to devising strategies to
      hasten viral eradication.

PMID- 9660367
TI  - Recovery of the immune system with antiretroviral therapy: the end of
      opportunism?
AB  - OBJECTIVE: Clinical care of people infected with human immunodeficiency virus
      (HIV) has been substantially affected by the introduction of potent
      antiretroviral therapy. Changes in the immune system after such therapy and the
      clinical consequences are important issues for clinicians treating patients with
      HIV. DATA SOURCES: A systematic review of MEDLINE, 1993 to January 1998, of peer
      reviewed publications, abstracts from national and international conferences, and
      product registration information through January 1998. STUDY SELECTION AND DATA
      EXTRACTION: Criteria used to select studies include relevance to immune
      reconstitution with potent antiretroviral therapy and having been published in
      the English language. Assessment of data quality and validity included
      consideration of venue of the publication and relevance to practice. DATA
      SYNTHESIS: Suppression of viral replication after administration of potent
      antiretroviral therapy that includes inhibitors of the HIV-1 protease is
      associated with quantitative and qualitative changes in the immune system. In
      patients with relatively advanced disease, there is a first-phase rise (during
      the initial 3 months) in both naive and memory CD4+ and CD8+ T lymphocytes and B
      lymphocytes. This is followed by a slower second-phase increase (after 3 months)
      in cells primarily of the naive CD4+ and CD8+ phenotypes. These quantitative
      changes are associated with qualitative improvements in host immune responses,
      best characterized by dramatically reduced risk of opportunistic infection.
      Restoration of the immune system during the first year of potent antiretroviral
      therapy is partial at best. CONCLUSIONS: Potent antiretroviral therapy has become
      the standard of care for people with HIV infection, and its use has led to
      significant reductions in the incidence of the acquired immunodeficiency syndrome
      (AIDS) and in mortality from HIV infection. Although incomplete, considerable
      immune recovery occurs, sufficient, in most cases, to provide adequate protection
      against most AIDS-associated opportunistic infections.

PMID- 9660369
TI  - HIV/AIDS in 1998--gaining the upper hand?

PMID- 9660370
TI  - A piece of my mind. Success and sadness.

PMID- 9660368
TI  - Antiretroviral therapy for HIV infection in 1998: updated recommendations of the
      International AIDS Society-USA Panel.
AB  - OBJECTIVE: To provide recommendations for antiretroviral therapy based on
      information available in mid-1998. PARTICIPANTS: An international panel of
      physicians with expertise in antiretroviral research and care of patients with
      human immunodeficiency virus (HIV) infection, first convened by the International
      AIDS Society-USA in December 1995. EVIDENCE: The panel reviewed available
      clinical and basic science study results (including phase 3 controlled trials;
      clinical, virologic, and immunologic end point data; data presented at research
      conferences; and studies of HIV pathophysiology); opinions of panel members were
      also considered. Recommendations were limited to drugs available in mid-1998.
      CONSENSUS PROCESS: Panel members monitor new clinical research reports and
      interim results. The full panel meets regularly to discuss how the new
      information may change treatment recommendations. Updated recommendations are
      developed through consensus of the entire panel at each stage of development.
      CONCLUSIONS: Accumulating data from clinical and pathogenesis studies continue to
      support early institution of potent antiretroviral therapy in patients with HIV
      infection. A variety of combination regimens show potency, expanding choices for
      initial regimens for individual patients. Plasma HIV RNA assays with increased
      sensitivity are important in monitoring therapeutic response; however, more data
      are needed to determine precisely the HIV RNA levels that define treatment
      failure. Long-term adverse drug effects are beginning to emerge, requiring
      ongoing attention. Some issues regarding optimal long-term approaches to
      antiretroviral management are unresolved. The increased complexity in HIV
      management requires ongoing monitoring of new data for optimal treatment of HIV
      infection.

PMID- 9660371
TI  - Treat HIV-1 infection like other infections--treat it.

PMID- 9660372
TI  - The case for conservative management of early HIV disease.

PMID- 9660373
TI  - JAMA patient page: HIV/AIDS.

PMID- 9660374
TI  - Posthyperventilatory steal response in chronic cerebral hemodynamic stress: a
      positron emission tomography study.
AB  - BACKGROUND AND PURPOSE: The alteration of regional cerebral blood flow (CBF)
      during and after hyperventilation was measured using positron emission tomography
      (PET) to determine the circulatory response induced by daily respiratory changes
      in the cerebral area under chronic hemodynamic stress. METHODS: Three normal
      volunteers and 12 patients with an obstruction of major cerebral arteries
      underwent PET measurements of the CBF after an injection of H2(15)O: (1) in the
      resting condition, (2) during hyperventilation (HV scan), (3) 1 to 3 minutes
      after hyperventilation (post-HV scan), (4) during the inhalation of 5% CO2, and
      (5) after an injection of acetazolamide. Eleven patients also underwent a 15O gas
      study to measure CBF, oxygen extraction fraction (OEF), and cerebral blood volume
      (CBV). RESULTS: (1) In 9 patients, the CBF value in the post-HV scan was lower
      than that in the HV scan in 1 or more regions in the area of the obstructed
      arteries, although the PaCO2 level during the post-HV scan was higher than that
      during the HV scan in all patients. All control regions in the patients and in
      the normal volunteers showed an elevated CBF in the post-HV scan compared with
      the HV scan. (2) The negative post-HV response (posthyperventilatory steal) was
      prominent in 4 patients with moyamoya vessels and in another 5 patients with
      atherosclerotic disease who had PET evidence of hemodynamic stress (elevated CBV
      or OEF). (3) The regional pre- to post-HV change in CBF was significantly
      correlated with the CBF responses to acetazolamide and CO2. CONCLUSIONS:
      Vasodilatation after the termination of hyperventilation in the normal areas
      induces a steal response in the cerebral area suffering from hemodynamic stress
      and may cause profound hypoperfusion in everyday situations. This phenomenon may
      be important to our understanding of the clinical symptoms and the natural course
      of chronic cerebral occlusive disease bearing hemodynamic stress.

PMID- 9660375
TI  - Diminished serotonin-mediated prolactin responses in nondepressed stroke patients
      compared with healthy normal subjects.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to use hormonal
      responsiveness to d-fenfluramine (d-FEN) challenge as a measure of central
      serotonin (5-HT) function in a comparative evaluation of serotonergic
      abnormalities between stroke patients and healthy elderly normal subjects to test
      the hypothesis that stroke may be associated with diminished serotonergic
      functioning. METHODS: Eight nondepressed medically stable stroke patients and 12
      healthy volunteers completed a single-blind, placebo-controlled, fixed-order,
      crossover design challenge test with 30 mg of oral d-FEN. Baseline prolactin
      (PRL) and cortisol (CORT) and hormonal responses to d-FEN and placebo were
      measured at hourly intervals over a 4-hour period. Cardiovascular responses
      (pulse and blood pressure) and behavioral responses were also recorded at the
      same time points. RESULTS: The 2 groups were comparable in demographics, body
      weight, plasma drug concentration, and behavioral and CORT responses. A 3-way
      ANOVA for repeated measures showed group differences for baseline adjusted PRL
      responses (change of scores from baseline). Peak PRL responses (maximal PRL
      change from baseline scores after treatment with d-FEN) in nondepressed stroke
      patients were attenuated compared with healthy elderly subjects, suggesting
      diminished serotonergic responsiveness in stroke patients. CONCLUSIONS: The
      demonstrated serotonergic hypofunctioning poststroke may contribute to the high
      incidence of depressive disorders in stroke patients. Serotonergic agents may
      have a role in augmentation of stroke recovery.

PMID- 9660376
TI  - Language-activated cerebral blood oxygenation and hemodynamic changes of the left
      prefrontal cortex in poststroke aphasic patients: a near-infrared spectroscopy
      study.
AB  - BACKGROUND AND PURPOSE: In normal subjects, regional cerebral blood flow (rCBF)
      is greatly increased by neuronal activity, whereas the cerebral metabolic rate
      for O2 is increased only slightly. However, it is not clear what kinds of
      cerebral blood oxygenation and hemodynamic changes can be induced by language
      activities in language-relevant areas of poststroke aphasics. In the present
      study, we investigated the difference in the changes of cerebral blood
      oxygenation and hemodynamics in the left prefrontal cortex induced by language
      activities between normal subjects, poststroke nonaphasic patients, and nonfluent
      aphasic patients using near-infrared spectroscopy (NIRS). METHODS: Twenty-nine
      participants performed speech tasks, such as confrontational naming, to evaluate
      changes among poststroke nonfluent (Broca's) aphasia patients (10 cases; mean+/
      SEM, 56.9+/-2.2 years), age-matched normal subjects (13 cases; 50.7+/-2.2 years)
      and poststroke nonaphasic patients (6 cases; 52.5+/-3.9 years). The optodes of
      NIRS were placed over the left prefrontal cortex. We analyzed the NIRS parameter
      (oxyhemoglobin [oxy-Hb], deoxyhemoglobin [deoxy-Hb], and total hemoglobin [total
      Hb]) changes by qualitative pattern analysis of the parameter changes and
      quantitative analysis of the parameter values among the groups. RESULTS: The most
      common NIRS parameter change was an increase in oxy-Hb and total-Hb, with a
      slight decrease or no change in deoxy-Hb in the normal subjects (5 of 13 cases,
      38.5%) and the nonaphasic cerebrovascular disease (CVD) patients (3 of 6 cases,
      50.0%). In contrast, the most common pattern in the aphasic patients was an
      increase of deoxy-Hb, with an increase of oxy-Hb and total-Hb (5 of 10 cases,
      50%). However, this pattern was observed in only 3 of 13 cases (23.1%) in the
      normal subjects and 1 of 6 cases (16.7%) in the nonaphasic CVD patients. The mean
      (+/-SEM) changes of deoxy-Hb of the aphasic patients, the normal subjects, and
      the nonaphasic CVD patients were 0.78+/-0.29, 0.06+/-0.16, and -0.18 +/- 0.22,
      respectively. The statistical analysis demonstrated a significant effect for
      deoxy-Hb (P<0.05), with the aphasic patients differing significantly from the
      normal subjects and the nonaphasic CVD patients, while the 2 nonaphasic groups
      did not differ from each other. CONCLUSIONS: The present results demonstrate a
      multiplicity of language-activated cerebral blood oxygenation and hemodynamic
      changes in the left prefrontal cortex in the nonaphasic and aphasic groups. The
      increase of deoxy-Hb with increases of oxy-Hb and total-Hb in the aphasics during
      language tasks suggests that the left prefrontal cortex of the aphasics utilizes
      more oxygen than the nonaphasics during language tasks. Finally, functional MRI,
      which images the activation area in the brain by detecting the reduced
      concentration of deoxy-Hb during neuronal activation, should be performed on the
      patients with cerebral dysfunction, giving special consideration to the possible
      multiplicity of the rCBF and cerebral oxygen metabolism responses to functional
      tasks.

PMID- 9660377
TI  - Bilateral hemispheric activation in the early recovery of motor function after
      stroke.
AB  - BACKGROUND AND PURPOSE: Functional recovery after cerebral infarction is a
      complex phenomenon that depends on various factors. The aim of this study was to
      investigate changes in cerebral perfusion during motor activity in stroke
      patients with very early recovery of motor function. METHODS: We included 9
      consecutive patients hospitalized for acute-onset hemiparesis who showed complete
      functional recovery within 24 hours. CT of the brain showed an ischemic or
      hemorrhagic cerebral lesion in areas compatible with the symptomatology. Within
      36 hours (range, 28 to 36) all patients were examined for the effects of a thumb
      to-finger opposition task on cerebral blood flow in the middle cerebral arteries,
      evaluated by means of bilateral transcranial Doppler ultrasonography. Data were
      compared with those of 9 healthy subjects matched for age and sex. In patients,
      the evaluation was repeated 2 to 4 months later. RESULTS: A comparable increase
      in flow velocity (% mean+/-SD) was observed with respect to baseline in the
      contralateral middle cerebral artery during motor activity with patients' normal
      (8.8+/-2.0%) and recovered hand (9.7+/-4.1%) and with both hands of control
      subjects (10.6+/-1.4%). In the middle cerebral artery ipsilateral to the hand
      performing the motor task, the increase in flow velocity was significantly higher
      (P<0.0001) during movement of the recovered hand in patients (8.6+/-2.7%) than
      during movement of the normal hand in both patients (2.6+/-1.6%) and control
      subjects (1.4+/-0.7%). In patients, pattern of changes in flow velocity during
      motor performance remained the same in the second evaluation. CONCLUSIONS: These
      observations suggest that areas of the healthy hemisphere can be activated soon
      after a focal injury and contribute to the positive evolution of a functional
      deficit in some patients. This phenomenon of ipsilateral activation cannot be
      considered transient because it is evident months after stroke onset.

PMID- 9660378
TI  - Changes of cerebrovascular CO2 reactivity during normal aging.
AB  - BACKGROUND AND PURPOSE: During the past decade, transcranial Doppler sonography
      has widely been used to assess blood flow velocities in the basal intracranial
      arteries and cerebrovascular reactivity (CR) to various stimuli. Although
      numerous studies have shown a decline of cerebral blood flow velocity with age,
      the age dependency of CR, including cerebrovascular CO2 reactivity, however, is
      controversial. Recently, we have reported a significant sex-related difference in
      CR, stressing the need to study the relation between normal aging and CR in both
      sexes separately. METHODS: By means of transcranial Doppler sonography, CR was
      determined in 100 healthy, nonsmoking volunteers (age 20 to 70 years, 10 men and
      10 women per decade). RESULTS: In men, no change of CR with increasing age could
      be observed (P=0.98). In contrast, CR in women declined significantly, with a
      step decrease from the 4th to the 5th decades (F=4.413; P<0.01) and was
      significantly higher in the 3rd and 4th compared with the 5th, 6th, and 7th
      decades (P<0.05). Information on hormone replacement therapy (HRT) in women of
      the 6th and 7th decades was obtained retrospectively. HRT was associated with
      enhanced CR (HRT, n = 7 versus non-HRT, n = 13; P<0.001), with values similar to
      those found in premenopausal women. CONCLUSIONS: There are no changes of CR
      during normal aging in men, whereas CR declines significantly from the 4th to the
      5th decades in women. HRT in postmenopausal women appears to enhance CR.

PMID- 9660379
TI  - Is visible infarction on computed tomography associated with an adverse prognosis
      in acute ischemic stroke?
AB  - BACKGROUND AND PURPOSE: It is unclear whether visible infarction on a CT scan at
      any time after the stroke is an adverse prognostic factor once other factors such
      as stroke severity are taken into consideration. We examined whether visible
      infarction was associated with a poor outcome after stroke using univariate and
      multivariate analyses, including easily identifiable clinical baseline variables,
      and adjusting for time from stroke onset to CT. METHODS: All inpatients and
      outpatients with an acute ischemic stroke attending our hospital stroke service
      were examined by a stroke physician and entered into a register prospectively.
      The CT scan was coded prospectively for the site and size of any relevant recent
      visible infarct. The patients were followed up at 6 months to ascertain their
      functional status with the use of the modified Rankin Scale. Analyses of the
      effect of visible infarction on the outcomes "dead or dependent" or "dead" at 6
      months were performed with adjustment for time from stroke to CT, clinical stroke
      type (lacunar, hemispheric, or posterior circulation), and in a multiple logistic
      regression model to adjust for confounding baseline variables such as stroke
      severity. RESULTS: In 993 patients in the stroke registry, visible infarction
      increased the risk of being dead or dependent at 6 months (odds ratio [OR], 2.5;
      95% confidence interval [CI], 1.9 to 3.3) or dead (OR, 4.5; 95% CI, 2.7 to 7.5),
      both on its own and after adjustment for time from stroke to CT, stroke symptoms,
      and other important clinical prognostic variables (OR for death or dependence in
      the predictive model, 1.5; 95% CI, 1.0 to 2.0; OR for death, 2.4; 95% CI, 1.4 to
      4.1). CONCLUSIONS: Visible infarction on CT is an adverse prognostic indicator
      (albeit of borderline significance) even after adjustment for stroke severity and
      time lapse between the stroke and the CT scan.

PMID- 9660380
TI  - Cerebral hypoperfusion during acute Kawasaki disease.
AB  - BACKGROUND AND PURPOSE: Kawasaki disease is a febrile disease of children notable
      for systemic vasculitis. There have been many previous reports of various
      complications, including disorders of the central nervous system. We evaluated
      cerebral perfusion during the acute stage in patients with Kawasaki disease.
      METHODS: Single-photon emission-computed tomography (SPECT) with 99mTc
      hexamethylpropyleneamine oxime was performed in 21 children with acute stage
      Kawasaki disease. Follow-up SPECT and MRI were performed about 1 month after the
      first SPECT in patients who exhibited abnormal SPECT findings during the acute
      stage. RESULTS: In 6 of 21 children SPECT imaging demonstrated localized cerebral
      hypoperfusion without abnormal neurological findings or clinical symptoms, and
      the follow-up SPECT and MRI approximately 1 month after the first SPECT revealed
      no abnormalities. CONCLUSIONS: Some patients with Kawasaki disease have transient
      localized cerebral hypoperfusion at the acute stage.

PMID- 9660381
TI  - The need to quantify right-to-left shunt in acute ischemic stroke: a case-control
      study.
AB  - BACKGROUND AND PURPOSE: Although right-to-left shunt (RLSh) has been reported to
      be significantly more frequent in young stroke patients with cryptogenic stroke,
      its relevance in a nonselected population of acute ischemic stroke is not well
      known. The aim of this study was to determine the importance of the RLSh
      magnitude as a risk factor for stroke in nonselected patients. METHODS: Two
      hundred eight patients hospitalized consecutively with transient ischemic attack
      or acute cerebral infarction and 100 healthy control subjects were studied.
      Transcranial Doppler ultrasonography (TCD) was performed in both middle cerebral
      arteries (MCAs) after intravenous application of agitated saline solution. The
      magnitude of RLSh was quantified by counting the number of signals in 1 MCA
      during a Valsalva maneuver. RLSh was classified as "no shunt," "small" (< 10
      signals), and "large" (> 10 signals), with the latter including the "shower" (>
      25 signals) and "curtain" (uncountable signals) patterns. Extensive
      investigations, including contrast transesophageal echocardiography, were carried
      out on patients diagnosed as suffering from stroke of an uncertain etiology. The
      importance of RLSh for stroke was assessed by logistic regression analysis.
      RESULTS: Contrast TCD detected a large RLSh in 40 (19.7%) patients and in 21
      (21%) control subjects, all with cardiac RLSh characteristics. A large RLSh was
      present in 4.7% of atherothrombotic strokes, 10.5% of cardioembolic strokes,
      15.4% of lacunar strokes, and 45.3% of cryptogenic strokes (P<0.001). Although
      the overall frequency of RLSh was not significantly different between patients
      and control subjects, the detection of curtain or shower patterns by contrast TCD
      was associated with a higher risk of stroke (odds ratio, 3.5; 95% confidence
      interval, 1.29 to 9.87), particularly with cryptogenic stroke (odds ratio, 12.4;
      95% confidence interval, 4.08 to 38.09) after adjustment for concomitant vascular
      risk factors. CONCLUSIONS: It is essential to quantify RLSh by contrast TCD
      during the Valsalva maneuver given that only those with shower and curtain
      patterns are associated with a higher risk of ischemic stroke in a nonselected
      population.

PMID- 9660382
TI  - Impaired glucose tolerance and the likelihood of nonfatal stroke and myocardial
      infarction: the Third National Health and Nutrition Examination Survey.
AB  - BACKGROUND AND PURPOSE: Although diabetes mellitus (DM) is known to increase the
      risk of cardiovascular disease (CVD), the effect of impaired glucose tolerance
      (IGT) on the risk remains unclear. We determined whether IGT was associated with
      an increased likelihood for stroke and myocardial infarction in a nationally
      representative sample of US adults. METHODS: We evaluated the association between
      IGT (defined as a fasting glucose level of < 140 mg/dL and a plasma glucose level
      of between 140 and 200 mg/dL 2 hours after administration of 75 grams of an oral
      glucose load) and DM (defined as the current use of insulin or an oral
      hypoglycemic medication, a fasting plasma glucose level of > 140 mg/dL, or a
      plasma glucose level of > 200 mg/dL 2 hours after administration of an oral
      glucose load) with a self-reported physician diagnosis of stroke and myocardial
      infarction in 6547 adults aged 40 to 74 years participating in the Third National
      Health and Nutrition Examination Survey. Multivariate logistic regression
      analyses were used to investigate these relationships. RESULTS: IGT and DM were
      observed in 1494 and 1532 adults, respectively. After adjustment for differences
      in age, gender, race/ethnicity, education, hypertension, cholesterol, body mass
      index, and cigarette smoking, IGT was not associated with stroke (odds ratio
      [OR], 0.9; 95% confidence interval [CI], 0.5 to 1.6) or myocardial infarction
      (OR, 1.1; 95% CI, 0.7 to 1.6). DM was associated with both stroke (OR, 1.6; 95%
      CI, 1.0 to 2.6) and myocardial infarction (OR, 1.9; 95% CI, 1.3 to 2.8).
      CONCLUSIONS: In contrast to DM, IGT was not associated with an increased
      likelihood of prevalent nonfatal stroke or myocardial infarction.

PMID- 9660383
TI  - Risk factors for stroke and type of stroke in persons with isolated systolic
      hypertension. Systolic Hypertension in the Elderly Program Cooperative Research
      Group.
AB  - BACKGROUND AND PURPOSE: We sought to determine risk factors for stroke and stroke
      type in persons with isolated systolic hypertension (ISH). METHODS: We performed
      proportional hazards analyses of data from the Systolic Hypertension in the
      Elderly Program, a double-blind, randomized, placebo-controlled trial of 4736
      persons aged > or =60 years with ISH (systolic blood pressure, 160 to 219 mm Hg;
      diastolic blood pressure, <90 mm Hg). One treatment group received chlorthalidone
      (12.5 to 25 mg/d) with step-up to atenolol (25.0 to 50.0 mg/d) or reserpine (0.05
      to 0.10 mg/d), if needed. The other treatment group received matching placebo.
      The main outcome measures were stroke, stroke or transient ischemic attack [TIA],
      and stroke types: ischemic (including lacunar, atherosclerotic, and embolic) and
      hemorrhagic. RESULTS: During an average follow-up of 4.5 years, 384 strokes or
      TIAs and 262 strokes (including 217 ischemic, 66 lacunar, 26 atherosclerotic, and
      25 embolic strokes) were documented. In multivariate analyses, placebo treatment,
      older age, smoking, history of diabetes, higher systolic blood pressure, lower
      HDL cholesterol, and ECG abnormality were significantly associated (P<0.05) with
      increased incidence of stroke or TIA, stroke, or ischemic stroke. Greater lacunar
      stroke risk was significantly related to placebo treatment, older age, history of
      diabetes (relative risk [RR] = 3.03; 95% confidence interval [CI], 1.70 to 5.40),
      and smoking (RR = 3.04; 95% CI, 1.73 to 5.37). Greater atherosclerotic and
      embolic stroke risk were significantly related to presence of carotid bruit (RR =
      5.75; 95% CI, 2.50 to 13.24) and older age (RR = 1.65 per 5 years; 95% CI, 1.25
      to 2.18), respectively. CONCLUSIONS: In older persons with ISH, history of
      diabetes and smoking are important risk factors for lacunar stroke, whereas
      carotid bruit and age are important risk factors for atherosclerotic and embolic
      stroke, respectively.

PMID- 9660384
TI  - Risk factors for ischemic stroke: Dubbo Study of the elderly.
AB  - BACKGROUND AND PURPOSE: One in 10 deaths in Australia is due to stroke. The
      predictors of ischemic stroke have not been well defined, although hypertension,
      atrial fibrillation, and previous stroke have been consistently reported. We
      report on 98 months' follow-up in a prospective study of cardiovascular disease
      in the Australian elderly, the Dubbo Study. METHODS: The cohort, first examined
      in 1988, was composed of 2805 men and women 60 years and older. The prediction of
      ischemic stroke by potential risk factors was examined in a Cox proportional
      hazards model, after linkage to hospital and death records. RESULTS: Three
      hundred six men and women manifested an ischemic stroke event (ICD-9-CM 433 to
      437), and 95 subjects suffered a fatal stroke event. In the multivariate model,
      the significant independent predictors of stroke were advancing age, female sex
      (48% lower risk), being married (30% lower risk), prior history of stroke (227%
      higher risk), use of antihypertensive drugs (37% higher risk), belonging to the
      highest category of blood pressure reading (67% higher risk), presence of atrial
      fibrillation (58% higher risk), HDL cholesterol (36% lower risk for each 1-mmol/L
      increment), impaired peak expiratory flow (77% higher risk for tertile I than for
      tertile III), physical disability (59% higher risk), and depression score (41%
      higher risk for tertile III than for tertile I). CONCLUSIONS: These findings
      suggest that morbidity and mortality associated with ischemic stroke can be
      predicted by various clinical indicators, some of which may be amenable to
      intervention. The matters of impaired peak expiratory flow, depression score, and
      ischemic stroke require further study.

PMID- 9660385
TI  - Clinical features of moyamoya disease in the United States.
AB  - BACKGROUND AND PURPOSE: We report the clinical features and longitudinal outcome
      of the largest cohort of patients with moyamoya disease described from a single
      institution in the western hemisphere. Moyamoya disease in Asia usually presents
      with ischemic stroke in children and intracranial hemorrhage in adults. METHODS:
      Our study population included all patients with moyamoya disease evaluated at a
      university hospital in Houston, Texas from 1985 through 1995 (n = 35). We used
      Kaplan-Meier methods to estimate individual and hemispheric stroke risk by
      treatment status (medical versus surgical). Predictors of neurological outcome
      were assessed. RESULTS: The ethnic background of our patients was representative
      of the general population in Texas. The mean age at diagnosis was 32 years
      (range, 6 to 59 years). Ischemic stroke or transient ischemic attack was the
      predominant initial symptom in both adults and children. Of the 6 patients with
      intracranial hemorrhage, 5 had an intraventricular site of hemorrhage. The crude
      stroke recurrence rate was 10.3% per year in 116 patient-years of follow-up.
      Twenty patients underwent surgical revascularization, the most common procedure
      being encephaloduroarteriosynangiosis. The 5-year risk of ipsilateral stroke
      after synangiosis was 15%, compared with 20% for medical treatment and 22%
      overall for surgery. CONCLUSIONS: Our observations indicate that moyamoya disease
      may have a different clinical expression in the United States than in Asia, and
      may demonstrate a trend toward a lower stroke recurrence rate and better
      functional outcome after synangiosis.

PMID- 9660386
TI  - Hydrocephalus: a previously unrecognized predictor of poor outcome from
      supratentorial intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: Although several factors have been identified that
      predict outcome after intracerebral hemorrhage (ICH), no previous study has
      investigated the impact of hydrocephalus. The purpose of this study was to
      determine whether the presence of hydrocephalus after ICH would predict mortality
      and functional outcome. METHODS: Patients with spontaneous supratentorial ICH
      were identified in our prospectively collected database to determine the
      following: age, sex, race, past medical history; Glasgow Coma Scale (GCS) score
      and blood pressure on admission; use of mechanical ventilation, mannitol, and
      ventriculostomy; and medical complications. CT scans performed within 24 hours of
      hemorrhage were retrospectively analyzed to determine lesion size and location,
      pineal shift, cisternal effacement, intraventricular hemorrhage (IVH), and
      hydrocephalus. Outcome was determined with use of hospital disposition (dead,
      nursing home, rehabilitation, home) and functional outcome (Functional
      Independence Measure [FIM]) at 3 months. Patients with and without hydrocephalus
      were compared and univariate and multivariate analyses performed to determine
      whether hydrocephalus was an independent predictor of mortality. Data are
      presented as mean+/-SD. RESULTS: Of the 81 patients studied, 40 had
      hydrocephalus. Those with hydrocephalus were younger (57+/-15 versus 67+/-15
      years), had lower GCS scores (8.2+/-4.2 versus 11+/-2.9), were more likely to
      have ganglionic or thalamic hemorrhages, and were intubated more frequently (70%
      versus 27%). Hospital mortality was higher in patients with hydrocephalus (51%
      versus 2%), and fewer patients went home (21% versus 35%). Those who died had
      higher hydrocephalus scores (9.67+/-7.1 versus 5.75+/-4.5). Outcome was no
      different if a ventriculostomy was placed. The final logistic regression model
      included hydrocephalus score, gender, GCS, and pineal shift, and it correctly
      predicted 85% of patients as dead or alive. Multivariate analyses indicated that
      hydrocephalus is an independent predictor of mortality. CONCLUSIONS: We conclude
      that hydrocephalus is an independent predictor of mortality after ICH.

PMID- 9660387
TI  - Time trends in long-term survival after stroke: the Northern Sweden Multinational
      Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) study,
      1985-1994.
AB  - BACKGROUND AND PURPOSE: Stroke mortality rates and case fatality of stroke have
      declined since the beginning of the 1970s in Sweden, but the incidence of stroke
      has been stable. The aim of this study was to analyze trends in long-term
      survival after stroke. METHODS: Within the framework of the population-based WHO
      Multinational Monitoring of Trends and Determinants in Cardiovascular Disease
      (MONICA) Project, all acute stroke events were recorded in the age group 25 to 74
      years in northern Sweden during the period 1985 to 1994. All first-ever stroke
      patients were followed for information on vital status (minimum follow-up time
      was 1 year). Survival time was related to time period of stroke onset, stroke
      diagnosis, and concomitant diseases. RESULTS: Survival times for a total of 6819
      first-ever stroke patients (4057 men and 2762 women) were analyzed. Age-adjusted
      odds ratio for death within 1 year after stroke was 0.70 (95% confidence interval
      [CI], 0.55 to 0.88) in the period 1993 to 1994 as compared with the period 1985
      to 1986 in men and 0.69 (95% CI, 0.53 to 0.90) in women. Corresponding odds
      ratios were 0.73 in men and 0.70 in women among those who survived the first 28
      days. Similar improvements were seen for 3- and 5-year survival. Improvements in
      survival over time were most marked among patients with ischemic stroke. There
      was no improvement in survival over time among patients with the most severe
      deficits at onset. CONCLUSIONS: Gradually improved survival, both short and long
      term, was observed during the 10-year study period. The improvements are not
      explained by changes in known confounding prognostic factors.

PMID- 9660388
TI  - Opposing national stroke mortality trends in Poland and for African Americans and
      whites in the United States, 1968 to 1994.
AB  - BACKGROUND AND PURPOSE: The United States (US) has experienced declines in stroke
      mortality in contrast to the increases reported for Poland. As part of the Poland
      and US Agreement on Cardiovascular and Cardiopulmonary Research, stroke mortality
      trends in Polish and US subpopulations were compared in the context of cross
      population differences in competing causes of death and determinants of stroke.
      METHODS: Age-adjusted annual stroke, cardiovascular disease (CVD), non-CVD, and
      all-cause mortality rates were determined for men and women aged 35 to 64 and 65
      to 74 years from 1968 to 1994 for African Americans and US whites and in Poland.
      Mean annual percent changes of mortality rates were estimated during 1968 to 1980
      and 1981 to 1994 with the use of piecewise log-linear regression. RESULTS: US
      stroke mortality rates declined 3.7% to 4.8% annually during 1968 to 1980 and
      2.0% to 3.1% during 1981 to 1994, with similar declines in each ethnic, gender,
      and age group. Polish rates increased 3.3% to 5.5% annually for all age-gender
      groups in Poland during 1968 to 1980. Polish men aged 35 to 64 experienced
      increasing rates during 1981 to 1994 (1.6% annually), while Polish women and
      older men experienced slight declines or little change. Only Polish men aged 35
      to 64 years exhibited increases in stroke, CVD, and non-CVD mortality rates
      during both time intervals. CONCLUSIONS: Poland and the US experienced opposing
      stroke mortality rate trends between 1968 and 1994. These national and ethnic
      trends occurring in just one generation suggest major effects of lifestyle,
      socioenvironmental, and/or medical care determinants.

PMID- 9660389
TI  - Increased bone resorption during the first year after stroke.
AB  - BACKGROUND AND PURPOSE: Significant bone mineral density (BMD) reduction occurs
      in stroke patients on the hemiplegic side compared with the intact side. To
      elucidate the pathogenesis of hip fractures in this population, we measured serum
      markers of bone metabolism and BMD in the stroke patients within 1 year (early
      group) and between 1 and 2 years after onset of hemiplegia (long-term group).
      METHODS: Sera were collected from 51 patients from the early group and 93
      patients from the long-term group. All patients had hemiplegia. Sera were assayed
      for pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen
      (ICTP; a bone resorption marker) and bone Gla protein (a bone formation marker).
      The z score of BMD was determined in both second metacarpals. RESULTS: Serum ICTP
      concentrations (ng/mL) were higher in the early group (15.4+/-4.1) than in the
      long-term group (6.7+/-4.4). Bone Gla protein was normal or low in both groups.
      Multiple regression analysis identified Barthel Index, degree of hemiplegia, and
      illness duration as independent determinants of ICTP in the early group, whereas
      Barthel Index, degree of hemiplegia, and serum calcium were determinants of ICTP
      in the long-term group. There were statistically significant correlations between
      the z score of the hemiplegic side and age, Barthel Index, degree of hemiplegia,
      illness duration, 25-hydroxyvitamin D (25-OHD), and ICTP in the early group and
      between the z score and degree of hemiplegia and 25-OHD level in the long-term
      group. CONCLUSIONS: The pathogenesis of reduced BMD differed between the early
      and long-term stroke groups. These results suggest that in the early group,
      increased bone resorption caused by immobilization was responsible for osteopenia
      on the hemiplegic side, whereas the degree of hemiplegia and 25-OHD level were
      the determinants of osteopenia in the long-term group.

PMID- 9660390
TI  - Relationship between intima-media thickness in the common carotid artery and
      atherosclerosis in the carotid bifurcation.
AB  - BACKGROUND AND PURPOSE: An increase in intima-media thickness (IMT) in the common
      carotid artery (CCA) is commonly used as a marker of atherosclerosis. The purpose
      of this study was to investigate the relationship between IMT in the CCA and
      atherosclerosis in the carotid bifurcation. METHODS: 182 consecutive patients
      (mean age, 67 years) referred for carotid duplex scanning were included. We
      measured IMT and classified plaques by means of a high-resolution ultrasound
      technique. RESULTS: IMT was correlated to age, male gender, ischemic heart
      disease, and presence of plaques or stenoses in any of the carotid bifurcations.
      In men, IMT was larger on the left than on the right side. Plaques were seen in
      163 carotid bifurcations, in 45 of these with > 50% stenosis. On the left side
      but not on the right, there was a correlation between IMT in the CCA and presence
      of plaques or stenoses in the carotid bifurcation. Echogenic plaques were more
      common than echolucent, but the latter caused significantly more stenoses. No
      relationship was found between plaque echogenicity and IMT. CONCLUSIONS: IMT of
      the CCA is correlated to the degree of atherosclerosis in the carotid
      bifurcations in general and on the left side also to the presence of plaques or
      stenoses in the left carotid bifurcation. Our results support earlier
      observations suggesting faster development of carotid atherosclerosis on the left
      than on the right side. Echogenic plaques were more common and generally smaller
      than echolucent plaques, but there was no correlation between plaque echogenicity
      and IMT.

PMID- 9660391
TI  - Transoral carotid ultrasonography.
AB  - BACKGROUND AND PURPOSE: We attempted ultrasonographic evaluation of the distal
      extracranial internal carotid artery (ICA) using the transoral method (transoral
      carotid ultrasonography [TOCU]). METHODS: The subjects consisted of five healthy
      volunteers and seven stroke patients. Examinations were performed with a color
      Doppler flow imaging system equipped with convex array transducers (7 or 9.5
      MHz), originally designed for transrectal use. After local anesthesia of the
      pharynx, we inserted a probe covered with thin gum transorally, touching the tip
      to the pharyngeal posterolateral wall. We then attempted to detect the ICA and
      measure flow velocity of the distal extracranial ICA using principal images
      obtained by TOCU. RESULTS: TOCU was successfully performed in all subjects
      without any difficulty. In the healthy volunteers, the ICA was identified at a
      depth of 2.2+/-0.6 cm and visualized as a vertical linear vessel 2.9+/-0.3 cm in
      length and bent slightly backward. The diameter and mean flow velocity of the
      distal extracranial ICA were 4.7+/-0.2 mm and 50+/-7 cm/s, respectively. In the
      stroke patients, some remarkable findings were obtained, including a narrow ICA
      with low flow velocity in a patient with possible ICA dissection, a lucent echo
      without flow signal in a patient with acute cardioembolic ICA occlusion, and
      decreased ICA flow velocity in a patient with ipsilateral MCA stenosis.
      CONCLUSIONS: These preliminary data demonstrate the potential applicability of
      TOCU to the evaluation of flow in the far distal extracranial ICA. TOCU
      definitely warrants further investigation in patients with carotid artery
      disease.

PMID- 9660392
TI  - Prognosis of patients with symptomatic vertebral or basilar artery stenosis. The
      Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) Study Group.
AB  - BACKGROUND AND PURPOSE: There are limited data on the prognosis of patients with
      angiographically proved symptomatic stenosis of the intracranial vertebral artery
      or basilar artery. METHODS: We studied 68 patients with 50% to 99% stenosis of
      one of the following arteries: intracranial vertebral (n = 31), basilar (n = 28),
      posterior cerebral (PCA) (n = 6), or posterior inferior cerebellar (PICA) (n =
      3). All patients had previous transient ischemic attack or stroke in the
      territory of the stenotic artery and were treated with warfarin (n = 42) or
      aspirin (n = 26). Follow-up was by chart review and personal or telephone
      interview. RESULTS: During a median follow-up of 13.8 months, 15 patients (22%)
      had an ischemic stroke (4 fatal), 3 patients (4.5%) had a fatal myocardial
      infarction (MI) or sudden death, and 6 patients (9%) had a nonfatal MI. Stroke
      rates in any vascular territory (per 100 patient-years of follow-up) were 15.0 in
      patients with basilar artery stenosis, 13.7 in patients with vertebral artery
      stenosis, and 6.0 in patients with PCA or PICA stenosis. Stroke rates in the same
      territory as the stenotic artery (per 100 patient-years of follow-up) were 10.7
      in patients with basilar artery stenosis, 7.8 in patients with vertebral artery
      stenosis, and 6.0 in patients with PCA or PICA stenosis. CONCLUSIONS: Patients
      with symptomatic intracranial vertebral artery or basilar stenosis are at high
      risk of stroke, MI, or sudden death. Further studies are needed to clarify
      optimal therapy for these patients.

PMID- 9660393
TI  - An electrocardiographic criterion for diagnosis of patent foramen ovale
      associated with ischemic stroke.
AB  - BACKGROUND AND PURPOSE: An M-shaped bifid notch on the ascending branch, or on
      the zenith, of the R wave in inferior ECG leads (II, III, aVF), so called
      "crochetage," is an indicator of ostium secundum atrial septal defects. The
      pathophysiology underlying this finding remains unknown. A crochetage pattern has
      not been previously reported in patients with patent foramen ovale (PFO);
      however, the location of this defect and the secundum atrial septum are similar.
      The purpose of this study was to determine the prevalence of crochetage in
      cryptogenic stroke patients with or without PFO. METHODS: A conservative
      selection scheme was used to identify patients likely to have had PFO-associated
      strokes (ie, cryptogenic) and to exclude any structural, functional, or vascular
      heart disease responsible for ECG changes. All patients had a standard 12-lead
      ECG. The prevalence of crochetage in each group was determined. RESULTS: Sixty
      consecutive patients were studied (28 with echo-documented PFO and 32 echo
      negative control subjects). The crochetage pattern was present in at least 1
      inferior limb lead in 10 of 28 PFO patients (36%) and 3 of 32 control subjects
      (9%) (P<0.05). The sensitivity and specificity of the crochetage pattern for
      diagnosis of PFO in cryptogenic stroke cases were 36% and 91%, respectively;
      positive predictive value was 77%. CONCLUSIONS: The finding of an ECG crochetage
      pattern may help to identify stroke patients with PFO, may help to streamline
      their diagnostic workup, and may warrant future studies to determine its value in
      stratifying stroke risk in patients with PFO.

PMID- 9660394
TI  - Frequency of the 20210 G-->A mutation in the 3'-untranslated region of the
      prothrombin gene in 35 cases of cerebral venous thrombosis.
AB  - BACKGROUND AND PURPOSE: A novel sequence variation in the 3'-untranslated region
      of the prothrombin (factor II) gene (nucleotide 20210 G-->A) has been recently
      described as a risk factor for deep vein thrombosis and pulmonary embolism. It is
      found in approximately 1% to 4% of healthy subjects. We studied the frequency of
      this factor II variant in patients with cerebral venous thrombosis. METHODS: The
      20210A allele of the prothrombin gene was studied after DNA extraction,
      polymerase chain reaction amplification, and HindIII digestion in 35 patients
      with magnetic resonance imaging or angiographically confirmed cerebral venous
      thrombosis (23 women and 12 men, aged 11 to 71 years). RESULTS: Two patients
      (5.7%) had the 20210A allele of the prothrombin gene. Both had other risk factors
      for thrombosis (use of oral contraceptives and of intrathecal steroids).
      CONCLUSIONS: The 20210A allele of the prothrombin gene in association with other
      prothrombic factors may increase the risk of cerebral venous thrombosis, but case
      control studies will be necessary to clarify these associations.

PMID- 9660395
TI  - ACE, MTHFR, factor V Leiden, and APOE polymorphisms in patients with vascular and
      Alzheimer's dementia.
AB  - BACKGROUND AND PURPOSE: There is a growing interest in the use of genetic markers
      in the differential diagnosis of dementia. In the current study we examined the
      usefulness of genetic risk factors for vascular disease as markers for vascular
      dementia (VD). METHODS: The groups included 41 patients with VD, 49 patients with
      dementia of the Alzheimer's type, and 40 age-matched control subjects without
      dementia. These patients were genotyped for vascular disease-associated
      polymorphisms in the genes coding for methylenetetrahydrofolate reductase
      (MTHFR), angiotensin-converting enzyme (ACE), factor V Leiden (FVL), and a common
      genetic risk factor for AD, apolipoprotein E epsilon4 (APOE epsilon4). RESULTS:
      There was no significant association between ACE, MTHFR, and FVL genotypes with
      VD whether compared with subjects with AD or with control subjects. There was a
      higher frequency of APOE epsilon4 alleles in patients with AD (30%, P=0.016) and
      VD (26%, P=0.07) compared with control subjects (15%). CONCLUSIONS: VD is not
      associated with the genetic risk factors for vascular disease examined in this
      study, indicating that the pathogenesis of VD may differ from other vascular
      diseases.

PMID- 9660396
TI  - Increased endothelial expression of intercellular adhesion molecule-1 in
      symptomatic versus asymptomatic human carotid atherosclerotic plaque.
AB  - BACKGROUND AND PURPOSE: The mechanisms that cause carotid atherosclerotic plaque
      to become symptomatic remain unclear. Evidence suggests that mediators of
      inflammation are not only instrumental in the formation of plaque but may also be
      involved in the rapid progression of atheromatous lesions leading to plaque
      fissuring, endothelial injury, and intraluminal thrombosis. Our goal is to
      determine whether intercellular adhesion molecule-1 (ICAM-1), a known component
      of the inflammatory pathway, is preferentially expressed on symptomatic versus
      asymptomatic carotid plaques. METHODS: Carotid plaques from symptomatic (n = 25)
      and asymptomatic (n = 17) patients undergoing carotid endarterectomy with lesions
      involving >60% stenosis were snap-frozen at the time of surgery.
      Immunofluorescence studies were performed to measure the percentage of luminal
      endothelial surface that expressed ICAM-1. The relationships of stroke risk
      factors, white blood cell count, percent stenosis, and soluble ICAM-1 (sICAM-1)
      plasma levels to endothelial ICAM-1 expression were investigated. RESULTS: An
      increased expression of ICAM-1 was found in the high-grade regions of symptomatic
      (29.5%+/-2.4%, mean+/-SEM) versus asymptomatic (15.7%+/-2.7%, mean+/-SEM) plaques
      (P=0.002) and in the high-grade versus the low-grade region of symptomatic
      plaques (29.5+/-2.4, mean+/-SEM, versus 8.9+/-1.6; P<0.001). Plasma sICAM-1
      levels were not predictive of symptomatic disease, and no significant correlation
      between risk factor exposure and endothelial ICAM-1 expression was found.
      CONCLUSIONS: An elevation in ICAM-1 expression in symptomatic versus asymptomatic
      plaque suggests that mediators of inflammation are involved in the conversion of
      carotid plaque to a symptomatic state. The data also suggest a differential
      expression of ICAM-1, with a greater expression found in the high-grade region
      than in the low-grade region of the plaque specimen.

PMID- 9660397
TI  - Adenovirus-mediated gene transfer in vivo to cerebral blood vessels and
      perivascular tissue in mice.
AB  - BACKGROUND AND PURPOSE: Gene transfer to cerebral blood vessels has been
      accomplished in rats and dogs by injection of replication-deficient adenovirus
      into cerebrospinal fluid. In this study we examined transgene expression after
      injection of adenovirus into the cerebrospinal fluid of mice. Responses were
      observed in ICR mice and C57BL/6 mice, which are outbred and inbred strains,
      respectively. METHODS: We injected replication-deficient recombinant adenovirus
      expressing nuclear targeted beta-galactosidase, driven by either the Rous sarcoma
      virus promoter (AdRSV-betaGal) or the cytomegalovirus promoter (AdCMV-betaGal),
      into the cisterna magna of anesthetized ICR and C57BL/6 strains of mice. The
      brains were examined from 1 to 21 days after injection by chemiluminescent enzyme
      activity assay or histochemical staining. RESULTS: After injection of AdRSV
      betaGal, expression of beta-galactosidase in ICR mice peaked on day 7 and
      returned to basal by day 14. Expression of beta-galactosidase in C57BL/6 mice was
      maximal on days 7 to 14 and was minimal by day 21 after injection of AdRSV
      betaGal. After injection of AdCMV-betaGal in C57BL/6 mice, peak expression of
      transgene occurred on day 1 and was greatly diminished by day 3. Transgene
      expression was observed primarily on the ventral surface of the brain, with
      preferential expression in leptomeninges and adventitia along the major cerebral
      arteries of that region. CONCLUSIONS: Injection of recombinant adenovirus in the
      cisterna magna resulted in transgene expression in leptomeninges and perivascular
      tissue of cerebral blood vessels in two strains of mice. The CMV promoter
      elicited rapid but short-lived expression of the transgene, while the RSV
      promoter elicited slower, more sustained transgene expression. Expression of
      AdRSV transgene was prolonged in C57BL/6 mice compared with ICR mice. This
      approach for gene transfer may be useful to study cerebral vascular biology in
      genetically altered strains of mice.

PMID- 9660398
TI  - Reduction of ischemic brain injury by topical application of glial cell line
      derived neurotrophic factor after permanent middle cerebral artery occlusion in
      rats.
AB  - BACKGROUND AND PURPOSE: Glial cell line-derived neurotrophic factor (GDNF) plays
      important roles in the survival and recovery of some mature neurons under
      pathological conditions. However, the effect of GDNF in ameliorating ischemic
      brain injury has not been well documented. Therefore, we investigated a possible
      effect of GDNF on the changes of infarct size, brain edema, DNA fragmentation,
      and immunoreactivities for caspases after permanent middle cerebral artery
      occlusion (MCAO) in rats. METHODS: For the estimation of ischemic brain injury,
      we calculated the infarct size of MCA region and also measured the brain water
      content as edema formation at 24 hours after the MCAO. Terminal deoxynucleotidyl
      transferase-mediated dUTP-biotin in situ nick labeling (TUNEL) staining was
      performed for the detection of DNA fragmentation. Immunoreactivities for caspase
      1 (ICE), caspase-2 (Nedd-2), and caspase-3 (CPP32) were stained. RESULTS: Both
      infarct size and brain edema after permanent MCAO were significantly reduced by
      topical application of GDNF (48% and 30% decreases, P=0.01). TUNEL staining and
      immunoreactivities for caspases were markedly induced at 12 hours after permanent
      MCAO in the vehicle-treated animals. However, the spatial distribution of those
      immunohistochemically positive cells was dissociative in each caspase. Induction
      of TUNEL staining and immunoreactivities for caspases-1 and -3 was greatly
      reduced with GDNF treatment, whereas the reduction of caspase-2 staining was only
      minimum. CONCLUSIONS: These data suggest that the reduction of infarct size and
      brain edema by GDNF was greatly associated with the reduction of DNA
      fragmentation and apoptotic signals predominantly through caspases-1 and -3
      cascades.

PMID- 9660399
TI  - Modulation of basal and postischemic leukocyte-endothelial adherence by nitric
      oxide.
AB  - BACKGROUND AND PURPOSE: Recent studies indicate that leukocytes are important
      contributors to secondary vascular and parenchymal injury after cerebral
      ischemia. The present study was undertaken to define nitric oxide (NO)-based
      mechanisms that regulate leukocyte-endothelial interactions in the cerebral
      vasculature, how these mechanisms are affected by cerebral ischemia, and whether
      NO-based therapies can affect postischemic leukocyte dynamics. METHODS: Leukocyte
      adherence to pial venules of anesthetized newborn piglets was quantified by in
      situ fluorescence videomicroscopy through closed cranial windows during basal
      conditions and during reperfusion after 9 minutes of asphyxia. Nitric oxide
      synthase (NOS) was inhibited by local window superfusion of L-nitroarginine;
      superfusion of sodium nitroprusside was used to donate NO. RESULTS: Local
      inhibition of NOS under resting conditions increased leukocyte-endothelial
      adherence 2.2-fold and 3.9-fold over baseline values after 1 hour and 2 hours,
      respectively; this response was completely blocked by cosuperfusion with L
      arginine. Cosuperfusion of superoxide dismutase reversed L-nitroarginine-induced
      leukocyte adherence by 89% and 63% at these respective time points. The extent of
      acute leukocyte adherence elicited by NOS inhibition was similar in magnitude to
      that observed during the initial 2 hours of reperfusion after asphyxia. Leukocyte
      adherence was not additionally increased in asphyxic animals treated with L
      nitroarginine. Sodium nitroprusside robustly inhibited asphyxia-induced leukocyte
      adherence back to control levels. CONCLUSIONS: NO exerts a tonic antiadherent
      effect in the cerebral microcirculation by inactivation of adherence-promoting
      superoxide radical formation. Cerebral ischemia is associated with an inhibition
      of NOS or lower levels of NO, which results in leukocyte-endothelial adherence
      that can be prevented by NO donors. The latter may be useful therapeutically to
      prevent the purported vascular and parenchymal dysfunction and injury caused by
      activated leukocytes in ischemic brain.

PMID- 9660400
TI  - Tacrolimus (FK506) attenuates leukocyte accumulation after transient retinal
      ischemia.
AB  - BACKGROUND AND PURPOSE: Tacrolimus, an immunosuppressant agent, has been shown to
      reduce tissue injury and leukocyte accumulation after transient ischemia. This
      study was designed to evaluate quantitatively the inhibitory effects of
      tacrolimus on leukocyte rolling and on subsequent leukocyte accumulation in vivo
      after transient retinal ischemia and the protective effects of tacrolimus on
      ischemia-induced neural damage. METHODS: Retinal ischemia was induced for 60
      minutes in anesthetized pigmented rats by temporary ligation of the optic sheath.
      Tacrolimus was administered at 10 minutes after ischemic induction. At 4, 12, 24,
      and 48 hours after reperfusion, leukocyte behavior in the retinal
      microcirculation was evaluated in vivo with acridine orange digital fluorography.
      After 7 days of reperfusion, ischemia-induced retinal damage was evaluated
      histologically. RESULTS: Treatment with tacrolimus suppressed leukocyte rolling;
      the maximum number of rolling leukocytes was reduced by 60.1% at 12 hours after
      reperfusion (P<0.05). In tacrolimus-treated rats, the velocity of rolling
      leukocytes was significantly faster than in vehicle-treated rats (P<0.01). The
      subsequent leukocyte accumulation was reduced by 61.6% at 24 hours after
      reperfusion (P<0.01). Histological examination demonstrated the protective effect
      of tacrolimus on ischemia-induced retinal damage, which was more substantial in
      the inner retina (P<0.01). CONCLUSIONS: The present study demonstrated the
      inhibitory effect of tacrolimus on leukocyte rolling and on subsequent leukocyte
      accumulation and the therapeutic potency to neural injury after transient retinal
      ischemia.

PMID- 9660401
TI  - Activation of protease-activated receptor-2 (PAR-2) elicits nitric oxide
      dependent dilatation of the basilar artery in vivo.
AB  - BACKGROUND AND PURPOSE: Protease-activated receptors (PARs) are a family of G
      protein-coupled receptors activated by a tethered ligand amino acid sequence
      within the amino terminal that is revealed by site-specific proteolysis. In the
      vascular endothelium, activation of PAR-2 by treatment with trypsin or by using
      the amino acid ligand sequence (SLIGRL) produces endothelium-dependent relaxation
      of isolated noncerebral vascular segments. In this study, we first tested whether
      PAR-2 activation produces cerebral vasodilatation in vivo and then examined
      whether PAR-2-mediated vasodilatation is dependent on the production of nitric
      oxide. METHODS: Concentration-dependent vasodilator effects of the PAR-2 agonist
      peptide SLIGRL and trypsin were examined on the basilar artery using a cranial
      window in anesthetized rats. In addition, the vasodilator effects of SLIGRL,
      acetylcholine (ACh), and sodium nitroprusside (SNP) were examined in the absence
      and presence of N(G)-nitro-L-arginine (L-NNA), an inhibitor of nitric oxide
      synthase, and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-l-one (ODQ), an inhibitor of
      soluble guanylate cyclase. RESULTS: Baseline diameter of the basilar artery
      averaged 239+/-4 microm. Under control conditions, SLIGRL (10(-6) to 10(-4)
      mol/L) and trypsin (0.01 to 10 U/mL) produced concentration-dependent vasodilator
      responses. In time-control experiments, SLIGRL (3 x 10(-6) and 10(-5) mol/L), ACh
      (10(-6) and 10(-5) mol/L), and SNP (10(-8) and 10(-7) mol/L) elicited
      reproducible dilatation of the basilar artery. In another group of rats, L-NNA
      (10(-4) mol/L) markedly inhibited dilator responses to both SLIGRL (13+/-3%
      versus 1+/-1% and 39+/-7% versus 11+/-2%; both P<0.05) and ACh (8+/-1% versus 0+/
      0% and 13+/-2% versus 3+/-1%; both P<0.05). By contrast, responses to SNP were
      significantly augmented after treatment with L-NNA (P<0.05 versus control),
      indicating that inhibitory effects of L-NNA were specific for responses mediated
      by endogenous nitric oxide. Furthermore, in another group ODQ (10(-5) mol/L)
      inhibited responses to SLIGRL to a degree similar to that seen with L-NNA,
      consistent with a mechanism of PAR-2-mediated vasodilatation that involves
      activation of guanylate cyclase by nitric oxide. CONCLUSIONS: To the best of our
      knowledge, this study is the first to examine whether PAR-2-mediated
      vasodilatation is functional in cerebral arteries and is also the first to
      directly assess the effects of PAR-2 activation on vascular tone in vivo. The
      results suggest that activation of PAR-2 is an effective and powerful vasodilator
      mechanism in cerebral arteries in vivo. Cerebral vasodilator responses to PAR-2
      activation are mediated by nitric oxide and are likely to be endothelium
      dependent.

PMID- 9660403
TI  - A model of transient unilateral focal ischemia with reperfusion in the P7
      neonatal rat: morphological changes indicative of apoptosis.
AB  - BACKGROUND AND PURPOSE: The mechanisms leading to delayed cell death after
      hypoxic-ischemic injury in the developing brain remain to be elucidated. The aim
      of this study was to develop a model of transient focal ischemia in the neonatal
      rat in an attempt to create a reperfusion phase since in the filament model of
      reversible middle cerebral artery occlusion, size limitations precluded
      performing this procedure before 14 to 18 days. We then analyze whether apoptosis
      or necrosis occurs in this model. METHODS: Seven-day-old Wistar rat pups (n = 96)
      underwent permanent left middle cerebral artery occlusion in association with 1
      hour occlusion of the left common carotid artery. Evolution of the brain
      infarction was studied from 24 hours to 3 months on cresyl violet-stained coronal
      sections. Infarct volume was determined with the use of the mitochondrial stain
      2,3,5-triphenyltetrazolium chloride. Neuronal death was demonstrated by the
      silver staining method of Gallyas et al (1980). Chromatin condensation was shown
      by DNA fragmentation assessed with the use of terminal deoxynucleotidyl
      transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay in cryostat
      sections and electron microscopic analysis. RESULTS: Almost all of the animals
      who survived had reproducible cortical infarcts. The mean infarct volume was 31+/
      7 mm3 (mean+/-SD). The ipsilateral hemisphere showed a well-delineated lesion in
      the frontoparietal cortex at 3-month recovery. Argyrophilic (dying) neurons were
      observed a few hours after reperfusion and increased with time. Cells exhibiting
      DNA fragmentation were shown as early as 6 hours, increased up to and peaked at
      24 to 96 hours, then progressively decreased and persisted for several days,
      suggesting an ongoing process. Electron microscopy analysis demonstrated high
      condensation and clumping of chromatin beneath nuclear membrane in shrunken
      neurons. CONCLUSIONS: Our study demonstrates the feasibility of performing
      ischemia-reperfusion in 7-day-old rats that develop progressive neuronal death
      with features characteristic of apoptosis. The reperfusion phase mimics events
      that occur during neonatal human hypoxic-ischemic encephalopathy at birth, since
      perinatal intensive care most often permits recirculation.

PMID- 9660404
TI  - Vasopressin combined with epinephrine decreases cerebral perfusion compared with
      vasopressin alone during cardiopulmonary resuscitation in pigs.
AB  - BACKGROUND AND PURPOSE: It is unknown whether a combination of vasopressin and
      epinephrine may be superior to vasopressin alone by targeting both nonadrenergic
      and adrenergic receptors. METHODS: After 15 minutes of cardiac arrest (13 minutes
      of ventricular fibrillation and 2 minutes of pulseless electrical activity) and 3
      minutes of chest compressions, 16 animals were randomly treated with either 0.8
      U/kg vasopressin (n = 8) or 0.8 U/kg vasopressin combined with 200 microg/kg
      epinephrine (n = 8). RESULTS: Comparison of vasopressin with vasopressin and
      epinephrine at 90 seconds and 5 minutes after drug administration resulted in
      comparable mean (+/-SEM) coronary perfusion pressure (54+/-3 versus 57+/-5 and
      36+/-4 versus 35+/-4 mm Hg, respectively), cerebral perfusion pressure (59+/-6
      versus 65+/-8 and 40+/-6 versus 39+/-6 mm Hg, respectively), and median (25th to
      75th percentiles) left ventricular myocardial blood flow [116 (81 to 143) versus
      108 (97 to 125) and 44 (35 to 81) versus 62 (42 to 74) mL x min(-1) x 100 g(-1),
      respectively], but significantly increased (P<0.05) total cerebral blood flow [81
      (77 to 95) versus 39 (34 to 58) and 50 (43 to 52) versus 28 (16 to 35) mL x min(
      1) x 100 g(-1), respectively]. Return of spontaneous circulation rates in both
      groups were comparable (vasopressin, 7 of 8; vasopressin and epinephrine, 6 of
      8). CONCLUSIONS: Comparison of vasopressin with vasopressin and epinephrine
      resulted in comparable left ventricular myocardial blood flow but significantly
      increased cerebral perfusion.

PMID- 9660402
TI  - Protein kinase C expression and activity after global incomplete cerebral
      ischemia in dogs.
AB  - BACKGROUND AND PURPOSE: Studies suggest that protein kinase C (PKC) activation
      during ischemia plays an important role in glutamate neurotoxicity and that PKC
      inhibition may be neuroprotective. We tested the hypothesis that elevations in
      the biochemical activity and protein expression of Ca2+-dependent PKC isoforms
      occur in hippocampus and cerebellum during the period of delayed
      neurodegeneration after mild brain ischemia. METHODS: We used a dog model of 20
      minutes of global incomplete ischemia followed by either 6 hours, 1 day, or 7
      days of recovery. Changes in PKC expression (Western blotting and
      immunocytochemistry) and biochemical activity were compared with neuropathology
      (percent ischemically damaged neurons) by means of hematoxylin and eosin
      staining. RESULTS: The percentage of ischemically damaged neurons increased from
      13+/-4% to 52+/-10% in CA1 and 24+/-11% to 69+/-6% in cerebellar Purkinje cells
      from 1 to 7 days, respectively. The occurrence of neuronal injury was accompanied
      by sustained increases in PKC activity (240% and 211% of control in hippocampus
      and cerebellum, respectively) and increased protein phosphorylation as detected
      by proteins containing phosphoserine residues. By Western blotting, the membrane
      enriched fraction showed postischemic changes in protein expression with
      increases of 146+/-64% of control in hippocampal PKCalpha and increases of 138+/
      38% of control in cerebellar PKCalpha, but no changes in PKCbeta and PKCgamma
      were observed. By immunocytochemistry, the neuropil of CA1 and CA4 in hippocampus
      and the radial glia in the molecular layer of cerebellum showed increased
      PKCalpha expression after ischemia. CONCLUSIONS: This study shows that during the
      period of progressive ischemic neurodegeneration there are regionally specific
      increases in PKC activity, isoform-specific increases in membrane-associated PKC,
      and elevated protein phosphorylation at serine sites.

PMID- 9660405
TI  - Altered function of inward rectifier potassium channels in cerebrovascular smooth
      muscle after ischemia/reperfusion.
AB  - BACKGROUND AND PURPOSE: Several recent studies have demonstrated that inward
      rectifier potassium channels (K(ir)s) are located on vascular smooth muscle of
      cerebral arteries in the rat. Activation of the K(ir)s dilates the arteries by
      relaxing the vascular smooth muscle. We tested the following hypothesis in the
      present study: function of inward rectifier potassium channels is altered after
      ischemia/reperfusion (I/R). METHODS: Temporary (2-hour) focal ischemia was
      induced in male Long-Evans rats (3% isoflurane anesthesia) by the intraluminal
      filament model. After 24 hours of reperfusion, ipsilateral and contralateral
      middle cerebral arteries (MCAs) were harvested and mounted on micropipettes,
      pressurized to 85 mm Hg, and luminally perfused. RESULTS: Resting diameters for
      contralateral (control) and ipsilateral (I/R) MCAs were not significantly
      different (215+/-4 microm and 211+/-5 microm [n = 6 and n = 7], respectively).
      Activation of the K(ir)s by abluminal administration of 15 mmol/L KCl to the
      control MCAs dilated the MCA by 34+/-4% (n = 8). Activation of the K(ir)s in I/R
      MCAs produced a dilation of only 11+/-3% (n = 8; P<0.001 compared with control).
      BaCl2 (75 micromol/L), a concentration-selective inhibitor of the K(ir)s,
      significantly attenuated the dilation produced by 15 mmol/L KCl in control MCAs
      but not in the I/R MCAs. Endothelial-mediated dilations elicited by the luminal
      administration of uridine triphosphate (10 micromol/L) produced similar dilations
      in both groups (32+/-5% for sham [n = 4] and 33+/-2% for I/R [n = 4]), indicating
      that dilator function in general was not altered in I/R vessels. CONCLUSIONS: We
      conclude that Kir function is altered after I/R. The Kir altered function is
      likely to exacerbate the brain injury occurring after I/R.

PMID- 9660406
TI  - Concerns regarding carotid endarterectomy guidelines.

PMID- 9660407
TI  - Ischemic strokes arriving too late for tPA are an ideal and ethical control group
      for continuing studies of tPA efficacy.

PMID- 9660408
TI  - Surgery for primary intracerebral hemorrhage: meta-analysis of CT-era studies.

PMID- 9660409
TI  - Apoptosis and matrix vesicles in the genesis of arterial aneurysms of cerebral
      arteries.

PMID- 9660410
TI  - Quantitative brain SPECT and the NIH Stroke Scale.

PMID- 9660411
TI  - Complications and outcome following acute stroke: revised table.

PMID- 9660412
TI  - Premature ovarian failure: an update.
AB  - OBJECTIVE: To present an overview of potential etiologies, clinical
      manifestations, and treatment modalities of premature ovarian failure (POF).
      DESIGN: A search of past and current articles on basic ovarian physiology and POF
      with use of MEDLINE. Additional information was obtained from an active study
      section on POF at the National Institutes of Health. Specific sections of this
      manuscript summarize the strengths and weaknesses of the possible
      pathophysiologic processes and management options of POF as they appear in the
      literature. RESULT(S): POF is not an uncommon disorder. Although the etiology
      remains elusive in most cases, several rare specific causes have been discovered.
      Although POF was once thought to be permanent, a substantial number of patients
      experience spontaneous remissions. Because of the association with other
      autoimmune diseases, close follow-up is recommended in patients with POF. Hormone
      replacement therapy remains the cornerstone of treatment, and the best chance of
      achieving a pregnancy is through oocyte donation. CONCLUSION(S): An understanding
      of basic ovarian embryology and physiology will allow clinicians to apply current
      treatments and develop new innovative therapies for their patients with POF.

PMID- 9660413
TI  - Subcutaneous autologous ovarian transplantation in Wistar rats maintains hormone
      secretion.

PMID- 9660414
TI  - Will ovarian autotransplantation have a role in reproductive and gynecological
      medicine?

PMID- 9660416
TI  - Updated projections of infertility in the United States: 1995-2025.
AB  - OBJECTIVE: To project the number of infertile women aged 15-44 every 5 years from
      2000 to 2025. DESIGN: Data are used from Cycle 5 of the National Survey of Family
      Growth conducted by the National Center for Health Statistics. Population
      projections prepared by the U.S. Bureau of the Census are used as the base
      population for 2000-2025. Prospective demographic projections are used to
      estimate the number of infertile women. PARTICIPANTS: The National Survey of
      Family Growth (Cycle 5) interviewed 10,847 women aged 15-44 in 1995. MAIN OUTCOME
      MEASURE(S): Number of infertile women. RESULT(S): The number of women
      experiencing infertility will range from 5.4-7.7 million in 2025, with the most
      likely number to be just under 6.5 million. CONCLUSION(S): This is a substantial
      revision (upward) in the number of infertile women, largely a result of the
      increase in the observed percentage of infertile women in 1995. This is the base
      population of concern to providers; of particular interest is the percentage of
      infertile women who seek medical treatment.

PMID- 9660415
TI  - The economic cost of infertility-related services: an examination of the
      Massachusetts infertility insurance mandate.
AB  - OBJECTIVE: To examine the costs and outcomes of infertility-related services in
      Massachusetts during a time of expanded use of assisted reproductive technology
      (ART). DESIGN: Cost data were obtained from the Massachusetts Department of
      Insurance Rate-Setting Commission and 9 large group insurance plans for the
      period 1986-1993. Utilization and success rates of ART were examined, and the
      cost per live delivery with the use of ART in 1993 was estimated. SETTING: The
      state of Massachusetts, in which access to infertility-related services has been
      mandated by law since 1989. PATIENT(S): The study population consisted of 8 large
      health maintenance organization plans and the Blue Cross/Blue Shield indemnity
      plan. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Per capita infertility
      related expenditures, infertility-related expenditures as a percentage of total
      expenditures, live deliveries per initiated ART cycle, and cost per live
      delivery. RESULT(S): Expenditures for infertility services increased at a rate
      similar to or slower than inflation during the years 1988-1992. Increases were
      slowest in health maintenance organizations, probably as a result of provider
      arrangements. Infertility services accounted for 0.41% of total expenditures
      within the indemnity plan in 1993 (approximately $1.71 per contract-month).
      Examination of ART utilization showed no evidence of overutilization by patients
      with a low chance of success. The cost per live delivery with the use of ART in
      1993 was $59,484. CONCLUSION(S): Mandated infertility coverage was associated
      with increased use of ART but not with excessive increases in consumer cost for
      infertility insurance coverage.

PMID- 9660417
TI  - Human immunodeficiency virus type 1--serodiscordant couples can bear healthy
      children after undergoing intrauterine insemination.
AB  - OBJECTIVE: To use semen from men who were seropositive for human immunodeficiency
      virus type 1 (HIV-1) to inseminate their partners without infecting them. DESIGN:
      Prospective study. SETTING: Private practice. PATIENT(S): Sixty-three HIV-1
      seropositive men and their HIV-1-seronegative female partners. INTERVENTION(S):
      The men provided 107 semen samples that were prepared with the use of the Percoll
      and swim-up techniques. The presence of HIV-1 was determined in the fraction of
      motile spermatozoa obtained after washing. If HIV-1 was not detected. IUI was
      performed in stimulated cycles. MAIN OUTCOME MEASURE(S): Human immunodeficiency
      virus type 1 RNA and DNA were detected with the use of the polymerase chain
      reaction technique modified for spermatozoa. RESULT(S): One hundred seven semen
      samples were washed. Human immunodeficiency virus type 1 was not detected in 101
      samples (94.4%) and was detected in 6 samples (5.6%). In the latter cases, IUI
      was not performed. One hundred one IUI procedures were performed in 63 women.
      Thirty-one pregnancies resulted, for a pregnancy rate of 30.7% per cycle and
      49.2% per inseminated woman. Thirty-seven healthy children were born. The results
      of tests for the detection of HIV-1 and antibodies to HIV-1 in the inseminated
      women were negative. CONCLUSION(S): On the basis of these results, testing for
      HIV-1 with the use of the polymerase chain reaction technique on the semen
      fraction obtained after washing appears to prevent infection in the inseminated
      woman. This method makes it possible to help HIV-1-seropositive men to have
      children without infecting their female partners.

PMID- 9660418
TI  - Crossover or parallel design in infertility trials? The discussion continues.
AB  - OBJECTIVE: To determine whether a crossover design results in a different
      estimate of treatment effect compared with a parallel design. DESIGN: With the
      aid of a computer program, data sets of subfertile patients were simulated under
      different assumptions. These patients were subjected to 2 treatments that were
      compared in either a parallel-design or a crossover-design trial. Results were
      analyzed using logistic regression. SETTING: University hospital. PATIENT(S):
      Simulated patients of a heterogeneous subfertile population. INTERVENTION(S): Two
      treatment modalities with a pregnancy rate of 10% and of 20% in the first cycle
      were offered for 6 cycles to simulated heterogeneous populations. MAIN OUTCOME
      MEASURE(S): After 1,000 simulations for each assumption, median pregnancy rates
      and odds ratios were compared between the crossover- and parallel-design trials.
      RESULT(S): No relevant difference in estimated treatment effect was found between
      the designs. The crossover design resulted in more pregnancies overall than the
      parallel design. CONCLUSION(S): In infertility research, parallel and crossover
      designs will lead to about the same results. Although the crossover design showed
      a slight tendency to overestimate the treatment effect of the most effective
      treatment, this overestimation is clinically not relevant and is small in
      relation to the random error. Because of its practical advantages and because
      more pregnancies are achieved, a crossover design should be the first choice in
      infertility research.

PMID- 9660419
TI  - Long-term down-regulation does not improve pregnancy rates in an in vitro
      fertilization program.
AB  - OBJECTIVE: To investigate the effects of long-term down-regulation (4 months)
      used in combination with gonadotropin ovarian stimulation for IVF-ET. DESIGN:
      Prospective randomized study. SETTING: Assisted Reproduction Unit of the Hospital
      Clinic i Provincial in Barcelona, a tertiary care setting. PATIENT(S): Thirty
      pairs of IVF patients who were matched for age, indication for IVF, and number of
      attempts. INTERVENTION(S): Women were randomized to receive a standard long
      protocol of SC leuprolide acetate (n = 30, group L) or a monthly injection of
      leuprolide acetate depot for 4 months (n = 30, group D) before gonadotropin
      stimulation. MAIN OUTCOME MEASURE(S): Ovarian response and IVF outcome.
      RESULT(S): Days of ovarian stimulation, follicular recruitment and growth during
      gonadotropin treatment, and the endometrial thickness on the day of hCG
      administration were similar for the 2 groups of IVF patients. However, the serum
      concentration of E2 was significantly higher in group L even though group D
      received a higher total dose of gonadotropins. The number of follicles punctured,
      the number of oocytes retrieved, the number of oocytes fertilized, the number of
      embryos suitable for replacement and cryopreservation, the number of patients
      with ET, and implantation and clinical pregnancy rates were similar for groups L
      and D. However, the percentage of metaphase II oocytes was significantly higher
      in group L than in group D. CONCLUSION(S): Long-term down-regulation does not
      improve pregnancy rates in a general IVF program.

PMID- 9660420
TI  - Genetic screening of prospective oocyte donors.
AB  - OBJECTIVE: To report our experience with genetic screening of oocyte donor
      candidates and to determine the frequency with which significant genetic issues
      are identified. DESIGN: Prospective genetic screening of oocyte donor candidates.
      SETTING: University hospital oocyte donation program. PATIENT(S): Women
      presenting consecutively as volunteer oocyte donors. INTERVENTION(S): Genetic
      screening was performed by pedigree analysis and laboratory studies. MAIN OUTCOME
      MEASURE(S): Inclusion in the oocyte donor pool based on the results of clinical
      evaluation and laboratory tests consisting of polymerase chain reaction based
      mutational analysis for cystic fibrosis carrier status, cytogenetic analysis for
      karyotype, enzymatic assay for Tay-Sachs disease carrier status, and complete
      blood count and hemoglobin electrophoresis. RESULT(S): Eight (11%) of 73 oocyte
      donor candidates were excluded from the donor pool because of a potentially
      serious genetic finding. Cystic fibrosis mutations were identified in 5
      candidates (7%), abnormal karyotypes were found in 2 (3.5%), and an autosomal
      dominant skeletal dysplasia was identified in 1 (1.4%). CONCLUSION(S): A
      significant proportion of women who present as candidates for oocyte donation are
      inappropriate for donation because of their genetic history or genetic testing
      results. A thorough genetic evaluation, including a history and laboratory
      screening, is essential to any oocyte donation program to maximize positive
      outcomes in pregnancies achieved through assisted means.

PMID- 9660421
TI  - Onset of the preovulatory luteinizing hormone surge: diurnal timing and critical
      follicular prerequisites.
AB  - OBJECTIVE: To determine the diurnal variation in the onset of the preovulatory LH
      surge in women. DESIGN: Prospective open cohort study. SETTING: University
      hospital research program. PATIENT(S): Thirty-five women with infertility
      resulting from tubal damage that was associated with minor endometriosis or with
      infertility of prolonged unexplained etiology. INTERVENTION(S): Women underwent
      transvaginal ultrasonography and serum E2 estimation daily during monitored
      cycles before unstimulated natural cycle IVF: exogenous gonadotropins were not
      administered. MAIN OUTCOME MEASURE(S): Serum E2 concentration, follicle diameter,
      and endometrial thickness. RESULTS: Of 169 cycles. 155 progressed to an ovulatory
      LH surge, of which 146 occurred within 8 hours of assessment of the outcome
      measures. The relationship between follicle diameter and E2 was weak, but an
      abnormal value for one always was countered by a normal value for the other.
      CONCLUSIONS: Most women begin the preovulatory LH surge between midnight and 8:00
      A.M., but with no particular variation by day of the week. The relationship
      between follicle size and serum E2 is not sufficiently strong to predict the LH
      surge confidently on the basis of only one variable, but the LH surge is unlikely
      to occur before either the follicle diameter has reached 15 mm and/or the serum
      E2 level has reached 600 pmol/L.

PMID- 9660422
TI  - Multinucleation in normally fertilized embryos is associated with an accelerated
      ovulation induction response and lower implantation and pregnancy rates in in
      vitro fertilization-embryo transfer cycles.
AB  - OBJECTIVE: To determine if multinucleation in normally fertilized embryos is
      indicative of poor developmental or clinical pregnancy prognosis and to examine
      the ovulation induction characteristics associated with multinucleation. DESIGN:
      Retrospective review. SETTING: A tertiary care institution. PATIENT(S): Patients
      undergoing IVF-ET cycles (exclusive of other assisted reproductive technologies).
      MAIN OUTCOME MEASURE(S): Cycles in which embryos had at least 1 multinucleated
      blastomere were compared with cycles in which all blastomeres exhibited no
      nucleus or a single nucleus (control). RESULT(S): When >50% of transferred
      embryos contained multinucleated blastomeres there was a significant reduction in
      implantation (3.4% vs. 14.7%), clinical pregnancy (9.1% vs. 29.1%), and live
      birth rates (7.5% vs. 27.6%) when compared with transfers of control embryos. In
      conjunction with this finding, multinucleate cycles had higher E2 levels and more
      follicles on the day of hCG administration, a higher number of oocytes retrieved,
      a higher fertilization rate, and more embryos transferred per patient than did
      the cycles that produced control embryos. When multinucleated embryos were
      present, but not transferred, the developmental capacity of the sibling embryo
      was reduced. CONCLUSION(S): The evaluation of nuclear status using simple light
      microscopy is predictive of embryo developmental capacity and should be included
      in the embryo scoring system. The presence of multinucleated blastomeres in
      normally fertilized embryos is associated with a more effusive response to
      gonadotropin therapy and is indicative of a poor developmental outcome and lower
      clinical pregnancy rates.

PMID- 9660423
TI  - Pregnancy and birth after transfer of embryos that developed from single
      nucleated zygotes obtained by injection of round spermatids into oocytes.
AB  - OBJECTIVE: To use injection of spermatids into oocytes as a mode of infertility
      treatment in cases in which spermatozoa are not available. DESIGN: Prospective
      clinical evaluation and case report. SETTING: In Vitro Fertilization Unit,
      Herzliya Medical Centers, Herzliya-on-Sea, Israel. PATIENT(S): Thirteen couples
      with male factor infertility in which the male partner lacked spermatozoa in the
      ejaculate or testicular biopsy samples. INTERVENTION(S): Round spermatid
      injection and elongated spermatid injection into oocytes. MAIN OUTCOME
      MEASURE(S): Evaluation of the rate of two-pronucleated and single-nucleated
      zygote development. RESULT(S): The rate of two-pronucleated zygote development
      after round spermatid injection and elongated spermatid injection was relatively
      low (27% and 36%, respectively). Single-nucleated zygotes develop more frequently
      after round spermatid injection and elongated spermatid injection (35% and 17%,
      respectively) than after intracytoplasmic sperm injection with mature
      spermatozoa. A normal pregnancy and childbirth resulted from the transfer of 4
      cleaving embryos, each of which developed from a single-nucleated zygote in a
      round spermatid injection treatment cycle with ejaculated spermatids.
      CONCLUSION(S): Embryos derived from single-nucleated zygotes after spermatid
      conception can be viable and give rise to an ongoing clinical pregnancy and
      childbirth.

PMID- 9660424
TI  - Induction of spermatogenesis and achievement of pregnancy after microsurgical
      varicocelectomy in men with azoospermia and severe oligoasthenospermia.
AB  - OBJECTIVE: To characterize treatment outcome after varicocele repair in men with
      azoospermia and severe oligoasthenospermia. DESIGN: Prospective nonrandomized
      study. SETTING: University-based medical center. PATIENT(S): Seventy-eight men
      with a palpable varicocele and absolute azoospermia (n = 22) or severe
      oligoasthenospermia (n = 56). INTERVENTION(S): Microsurgical varicocelectomy.
      MAIN OUTCOME MEASURE(S): Sperm count and pregnancy rate. RESULT(S): Twelve (55%)
      of the 22 men with azoospermia and 35 (69%) of the 51 men with zero motile sperm
      before surgery had motile sperm observed in their ejaculate after varicocele
      repair. The total number of motile sperm per ejaculate increased from 0.08 +/-
      0.02 x 10(6) before varicocelectomy to 7.2 +/- 2.3 x 10(6) afterward. Twenty-four
      men (31%) contributed to pregnancies leading to live births (15 unassisted
      [19%]), including 3 men with azoospermia preoperatively. CONCLUSION(S):
      Varicocele repair resulted in the induction or enhancement of spermatogenesis for
      most men with azoospermia or severe oligoasthenospermia. Unassisted pregnancies
      after varicocele repair in men with profound abnormalities of spermatogenesis are
      possible. Varicocele repair should be considered for all men with azoospermia and
      severe oligoasthenospermia.

PMID- 9660425
TI  - Canadian semen quality: an analysis of sperm density among eleven academic
      fertility centers.
AB  - OBJECTIVE: To determine whether sperm quality has declined among Canadian men
      during the past 13 years and whether there are regional differences in sperm
      quality. DESIGN: Retrospective temporal series of cross-sectional studies.
      SETTING: University fertility centers across Canada. PATIENT(S): Men being
      investigated as part of the normal infertility work-up. MAIN OUTCOME MEASURE(S):
      Sperm concentrations among all the samples were compared on an annual basis to
      assess any changes over 13 years from 1984 through 1996. RESULT(S): There were
      regional differences and trends in both up and down directions. Linear regression
      analysis of the means of each center for each year showed no significant trend.
      However, when all the samples were analyzed by regression analysis there was a
      significant downward trend. CONCLUSION(S): Linear regression analysis showed a
      significant downward trend in sperm concentration among 48,968 samples from
      Canadian men obtained from 1984 through 1996. A significant difference was seen
      in the mean concentrations between centers, ranging from 48.6 to 104.5 X
      10(6)/mL. Secular trends in sperm density are dependent on the statistical method
      used for analysis.

PMID- 9660426
TI  - Relation of endometriosis and neuromuscular disease of the gastrointestinal
      tract: new insights.
AB  - OBJECTIVE: To investigate the neuromuscular activity of the gastrointestinal
      tract by antroduodenal manometry in women with endometriosis documented by
      laparoscopy, to assess the effects of diet and drug therapy on symptoms, and to
      assess the bacterial overgrowth that is commonly associated with these nerve
      diseases. DESIGN: Prospective, open-label study. SETTING: A clinical center for
      the care of women's health. PATIENT(S): Fifty women with endometriosis documented
      by laparoscopy and gastrointestinal tract symptoms characterized by chronic
      abdominal pain, nausea, vomiting, early satiety, bloating and distention, and
      altered bowel habits. INTERVENTION(S): Motility of the gastrointestinal tract was
      recorded and bacterial overgrowth was assessed. Treatment consisted of dietary
      changes, including reduction of glycemic carbohydrates, balancing with omega 9
      oils, elimination of foods with caffeine and tyramine, and addition of omega 3
      fatty acids, as well as drug therapy with clonazepam (0.25 mg 3 times per day).
      RESULT(S): All 50 women showed a characteristic motility change (ampulla of Vater
      duodenal wall spasm, a seizure equivalent of the enteric nervous system). Forty
      of the women showed bacterial overgrowth. There was a significant reduction in
      the total symptom score after 8 weeks of treatment. CONCLUSION(S): This study
      suggests that endometriosis and gastrointestinal tract symptoms are a result of
      the dysfunction of hollow organs. Correction of the biochemical imbalance of the
      eicosanoid system and the hypersecretion of insulin that results from excessive
      intake of glycemic carbohydrates and lack of essential fatty acids significantly
      decreases symptoms in patients with endometriosis and associated neuromuscular
      disease of the gastrointestinal tract.

PMID- 9660427
TI  - 45,X/46,XX mosaicism in patients with idiopathic premature ovarian failure.
AB  - OBJECTIVE: To determine whether low-level 45,X/46,XX mosaicism may be present in
      some women with premature ovarian failure (POF). DESIGN: Slide preparations were
      made from lymphocyte cultures stimulated with phytohemagglutinin, and
      fluorescence in situ hybridization (FISH) was then performed using a biotin
      labeled X-chromosome probe. SETTING: Cytogenetics laboratory. PATIENT(S): Fifteen
      women with idiopathic POF, 20 age-matched controls, and an additional 10 older
      control women with normal reproductive histories. INTERVENTION(S): Blood samples
      were collected. MAIN OUTCOME MEASURE(S): The number of X chromosomes present in
      each cell. RESULT(S): In patients with POF, the percentage of cells with a single
      X chromosome (mean, 5.50) was significantly greater than in the controls of
      similar age (mean, 2.42). For control subjects, there appeared to be a linear
      correlation between the number of cells with a single X chromosome and age.
      CONCLUSION(S): Some cases of POF may be attributable to low-level 45,X/46,XX
      mosaicism, which can be detected using FISH. In the lymphocytes from normal
      women, the rate of accumulation of cells with a single X chromosome was
      approximately 700 per 10(6) cells per year.

PMID- 9660428
TI  - Pituitary desensitization to gonadotropin-releasing hormone increases abdominal
      adiposity in hyperandrogenic anovulatory women.
AB  - OBJECTIVE: To determine whether hyperandrogenism in anovulatory women affects
      body fat distribution. DESIGN: Prospective nonrandomized study. SETTING: An
      academic research environment. PATIENT(S): Ten hyperandrogenic anovulatory
      patients and 10 healthy women matched by body mass index. INTERVENTION(S):
      Regional body fat analysis was performed before and after 3 months of GnRH
      analogue (GnRH-a) therapy. MAIN OUTCOME MEASURE(S): Body fat distribution was
      measured by waist-to-hip circumference ratio, single-slice computed tomography
      imaging (L2-3 interspace), and total body dual-energy x-ray absorptiometry.
      RESULT(S): Weight, body mass index, waist-to-hip circumference ratio, total body
      and leg fat mass, and subcutaneous adipose area were unaffected by the presence
      of hyperandrogenism or the use of GnRH-a therapy. Basal abdominal fat mass,
      abdomen-to-leg fat mass ratio, visceral adipose area, and total visceral adipose
      volume were comparable in both study groups. The abdominal fat mass increased in
      both groups during GnRH-a therapy, whereas the abdomen-to-leg fat mass ratio rose
      significantly only in the hyperandrogenic patients. During GnRH-a therapy, the
      hyperandrogenic patients demonstrated a significant increase in visceral adipose
      area compared with the healthy women so that total visceral adipose volume
      increased significantly in the former but not the latter. CONCLUSION(S): Three
      months of GnRH-a administration preferentially increased abdominal fat, as
      measured by single-slice computed tomography imaging and total body dual-energy x
      ray absorptiometry, in hyperandrogenic anovulatory women.

PMID- 9660429
TI  - Immunoreactive gonadotropin-releasing hormone expression in cycling human
      endometrium of fertile patients.
AB  - OBJECTIVE: To investigate the protein expression of GnRH in the endometrium of
      fertile patients throughout the menstrual cycle. DESIGN: Prospective longitudinal
      study. SETTING: Department of Gynecology and Obstetrics, Reproductive Immunology
      Laboratory, Stanford University Medical Center. PATIENT(S): Twenty-two fertile
      premenopausal women submitted to laparoscopic surgery for benign gynecologic
      indications. None of the 22 women had endometriosis or pelvic inflammatory
      disease. INTERVENTION(S): An endometrial biopsy specimen using the Novak curette
      was obtained at the time of surgery. MAIN OUTCOME MEASURE(S): Protein expression
      and localization from unfractioned endometrial tissue was analyzed by
      immunohistochemistry. RESULT(S): Gonadotropin-releasing hormone is expressed at
      the protein level in both the endometrial stroma and epithelium throughout the
      entire menstrual cycle of fertile women. Immunostaining in the human epithelium
      reached maximal levels in the midluteal phase and was elevated in the stroma
      throughout the entire luteal phase. CONCLUSION(S): Our results demonstrate the
      presence of GnRH in the human endometrium at the protein level throughout the
      entire menstrual cycle of fertile women, with an increase in the luteal phase
      compared with the preovulatory endometrium.

PMID- 9660430
TI  - Postmenopausal dehydroepiandrosterone administration increases free insulin-like
      growth factor-I and decreases high-density lipoprotein: a six-month trial.
AB  - OBJECTIVE: To determine the effect of administering 6 months of oral
      postmenopausal DHEA therapy on serum DHEA, DHEAS, and T levels and on physiologic
      endpoints including lipoproteins and insulin-like growth factor-I (IGF-I).
      DESIGN: Randomized, double-blind, parallel trial. SETTING: Academic referral
      practice. PATIENT(S): Thirteen normal-weight or overweight, healthy, nonsmoking,
      postmenopausal women. INTERVENTION(S): Administration of oral micronized DHEA (25
      mg/d). MAIN OUTCOME MEASURE(S): Monthly fasting 23 hours postdose levels of serum
      DHEA, DHEAS, T, lipoproteins, IGF-I, IGF binding protein-3 (IGFBP-3), and liver
      function tests. Morphometric indices by dual-energy x-ray absorptiometry scan
      (percent body fat; lean body mass), immune indices, and insulin sensitivity.
      RESULT(S): Levels of DHEA, DHEAS, and T all rose into premenopausal ranges, but
      after 6 months, levels of DHEA and T did not differ from baseline or placebo. At
      3 months, the ratio of IGF-I to IGFBP-3 rose by 36.1% +/- 12.7%, but it fell to
      placebo values by 6 months. High-density lipoprotein and apolipoprotein A1 levels
      declined. CONCLUSION(S): Patients appeared to tolerate 6 months of DHEA therapy
      well. Given the small study size, no statistically significant differences in
      morphometric indices, immune indices, or insulin-sensitizing properties were
      observed, but significant attenuation of bioavailability occurred.
      Supplementation with DHEA increased IGF-I/IGFBP-3 levels at 3 months and
      decreased high-density lipoprotein and apolipoprotein A1 levels at 6 months.

PMID- 9660431
TI  - A clinical trial of the effects of tibolone administered with gonadotropin
      releasing hormone analogues for the treatment of uterine leiomyomata.
AB  - OBJECTIVE: To evaluate the effects of tibolone therapy in association with GnRH-a
      on uterine leiomyomata, on climacteric-like symptoms, on bone metabolism, and on
      the lipid profile. DESIGN: A prospective, randomized, double-blind, placebo
      controlled, clinical trial. SETTING: Department of Gynecology and Obstetrics,
      University of Naples "Federico II," Naples, Italy. PATIENT(S): Fifty women with
      symptomatic uterine leiomyomata. INTERVENTION(S): Six months of treatment with
      leuprolide acetate (3.75 mg every 28 days IM) combined with daily placebo tablets
      (group A) or with 2.5-mg of tibolone per os (group B). MAIN OUTCOME MEASURE(S):
      Uterine and uterine leiomyomata sizes, lumbar spine bone mineral density,
      biochemical markers of bone metabolism, lipid profile, and myoma-related symptoms
      were measured at baseline and after 6 months of treatment. Daily symptom diary in
      which hot flushes and vaginal bleeding episodes were recorded. RESULT(S): No
      differences between the 2 groups in uterine and uterine leiomyomata size and
      myoma-related symptoms were detected. After 6 months of treatment, there were
      statistically significant changes from baseline in bone mineral density and in
      biochemical markers of bone metabolism in group A but not in group B. Vasomotor
      symptoms were significantly lower in group B than in group A. There was a
      statistically significant increase (P<.01) in serum total cholesterol, high
      density lipoprotein cholesterol, and triglycerides in group A after 6 months of
      treatment in comparison with baseline values. The difference in serum total
      cholesterol and triglyceride levels after 6 months of treatment in group B was
      not statistically significant in comparison with baseline values, but was
      statistically significant in comparison with group A values (P<.01). In group B,
      levels of high-density lipoprotein cholesterol were significantly lower after 6
      months of therapy in comparison with baseline values and in comparison with group
      A values (P<.01). There were no statistically significant changes at baseline and
      after 6 months of treatment in the level of low-density lipoprotein cholesterol
      in either group. CONCLUSION(S): Administration of tibolone in association with
      GnRH-a reduces vasomotor symptoms and prevents bone loss, without compromising
      the therapeutic efficacy of GnRH-a alone.

PMID- 9660432
TI  - Dimeric inhibin: a direct marker of ovarian aging.
AB  - OBJECTIVE: To investigate whether luteal secretion of inhibin-a is altered in the
      perimenopausal transition and to evaluate whether luteal inhibin secretion is
      correlated with other markers of ovarian reserve such as FSH and inhibin-b.
      DESIGN: Prospective study. SETTING: Reproductive Endocrinology Laboratories at
      The Ohio State University. PATIENT(S): Twenty-five women 39-52 years of age with
      regular menstrual cycles. INTERVENTION(S): Daily urine samples were monitored (LH
      predictor kit) to identify the day of ovulation. Blood samples obtained on days 6
      and 8 after the LH surge and on day 3 of the subsequent follicular phase were
      assayed for FSH, E2, progesterone. inhibin-a, and inhibin-b. MAIN OUTCOME
      MEASURE(S): Serum levels of inhibin-a, inhibin-b, FSH, E2, and progesterone.
      RESULT(S): Luteal phase inhibin-a and follicular phase inhibin-b were correlated
      inversely with age in perimenopausal women. In addition, luteal phase inhibin-a
      and follicular phase inhibin-b levels were correlated inversely with follicular
      phase FSH levels. CONCLUSION(S): Both luteal phase inhibin-a and follicular phase
      inhibin-b levels are correlated inversely with age during the fifth decade of
      life. These findings suggest that corpus luteum function is altered during the
      perimenopausal transition. Moreover, these direct measures of ovarian function
      may be more sensitive indicators of "ovarian reserve" than indirect indicators
      such as pituitary FSH secretion.

PMID- 9660433
TI  - Freezing, thawing, and autograft of ovarian fragments in sheep: preliminary
      experiments and histologic assessment.
AB  - OBJECTIVE: To evaluate the effects of freezing and thawing on the histologic
      changes in ovarian fragments from sheep and to determine the feasibility of
      ovarian autografts. DESIGN: Histologic evaluation of follicles that survived
      after freezing at -196 degrees C for 2 weeks. Histologic evaluation of ovarian
      fragments 6 months after the autografts. SETTING: Laboratoire de Zootechnie,
      Ecole National Veterinaire, Marcy l'Etoile, France. ANIMAL(S): Six ewes aged 6
      months to 1 year. INTERVENTION(S): Cortical fragments were prepared from the
      right ovary of 6 lambs and were grafted immediately to the contralateral ovarian
      hilus or were cooled slowly to -196 degrees C in medium containing dimethyl
      sulfoxide for 2 weeks. The autografts were recovered 6 months later. RESULT(S):
      Histologic examination of ovarian slices after freezing showed no destruction of
      primordial, primary, secondary, or cavitary follicles. The ovarian autograft
      showed good recovery of the macroscopic and microscopic ovarian structure. After
      autografting, histologic examination revealed primordial to cavitary follicles.
      CONCLUSION(S): Freezing of ovarian fragments is possible without damaging the
      follicles. Ovarian autografts showed good recovery of ovarian structure.

PMID- 9660434
TI  - Transforming growth factor-beta1, insulin-like growth factors, and insulin-like
      growth factor binding proteins in ovarian follicular fluid are differentially
      regulated by the type of ovarian hyperstimulation used for in vitro
      fertilization.
AB  - OBJECTIVE: To determine the effects of hMG and highly purified FSH on follicular
      production of the ovarian growth factors transforming growth factor-beta1 (TGF
      beta1), insulin-like growth factors I and II (IGF-I and IGF-II), and insulin-like
      growth factor binding proteins-1 and -3 (IGFBP-1 and IGFBP-3). DESIGN: Controlled
      clinical study. SETTING: University IVF program. PATIENT(S): One hundred twenty
      women who were <38 years old and had a >3-year duration of infertility in their
      present relationship participated in the study. INTERVENTION(S): Follicular fluid
      and matched serum were collected at oocyte pick-up and analyzed for growth
      factors and E2 with the use of ELISA and RIA. MAIN OUTCOME MEASURE(S): Levels of
      TGF-beta1, IGF-I. IGF-II, IGFBP-1 and IGFBP-3 in follicular fluid and levels of
      E2 in serum were measured. RESULT(S): Compared with highly purified FSH, ovarian
      hyperstimulation with hMG produced lower levels of TGF-beta1 and IGF-I and higher
      levels of IGFBP-1. Levels of IGF-II and IGFBP-3 were similar with the 2
      treatments. CONCLUSION(S): In patients undergoing IVF, the follicular expression
      of TGF-beta1, IGF-I, and IGFBP-1 was regulated differently by highly purified FSH
      compared with a preparation containing FSH and LH in a 1:1 ratio (hMG). The
      results indicate that FSH and LH control ovarian production of these growth
      factors differentially.

PMID- 9660435
TI  - Localization of Bcl-2 in the human fetal mullerian tract.
AB  - OBJECTIVE: To determine if apoptosis is involved in development of the human
      fetal mullerian tract and regression of the uterine septum and to localize Bcl-2.
      a protein involved with regulating apoptosis. DESIGN: Descriptive controlled
      study. SETTING: Tertiary academic medical center. PATIENT(S): Eight human fetal
      uteri from 12 to 21 weeks' gestation. INTERVENTION(S): Immunohistochemistry using
      a monoclonal antibody for Bcl-2. MAIN OUTCOME MEASURE(S): Immunostaining.
      RESULTS: Bcl-2 was localized in endometrial cells, tubal muscularis and
      epithelium, and myometrial edges. It was absent from the septum of 4 uteri.
      CONCLUSIONS: The presence of Bcl-2 suggests that development of the human fetal
      mullerian tract involves apoptosis. Bcl-2 may protect the fetal endometrium from
      apoptosis as it continues to grow. The superior, inferior, and lateral myometrium
      as well as the tubal epithelium and muscularis also may represent active growth
      zones that are protected from apoptosis. The notable absence of staining for Bcl
      2 in the embryonal uterine septum may indicate lack of protection from apoptosis
      in this area. This finding supports our hypothesis that apoptosis may be a
      mechanism by which the uterine septum regresses.

PMID- 9660436
TI  - Insulin-like growth factor binding protein-3 reduction in follicular fluid in
      spontaneous and stimulated cycles.
AB  - OBJECTIVE: To investigate serum and follicular fluid insulin-like growth factor-I
      (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) behavior in
      spontaneous and in superstimulated cycles. DESIGN: Estradiol, GH, IGF-I, and
      IGFBP-3 were evaluated in serum and in follicular fluid during spontaneous and
      stimulated cycles. SETTING: Department of Obstetrics and Gynecology, University
      of Naples, Naples, Italy. PATIENT(S): Ninety-two patients with regular menstrual
      cycles and tubal and/or male factor infertility undergoing treatment with an IVF
      program. INTERVENTION(S): The superstimulated IVF program uses leuprolide acetate
      suppression followed by hMG in a sequential manner in the subsequent cycle. After
      sufficient follicular development, hCG was administered, followed 34-36 hours
      later by oocyte retrieval. MAIN OUTCOME MEASURE(S): Growth hormone, IGF-I, and
      IGFBP-3 were assayed by RIA and immunoradiometric assay techniques. RESULT(S):
      Growth hormone levels in serum and in follicular fluid were higher after FSH
      stimulated cycles than after physiologic cycles. Serum and follicular fluid IGF-I
      did not change during physiologic and FSH-stimulated cycles. Serum IGFBP-3
      decreased only in FSH-stimulated cycles. Levels of IGFBP-3 in follicular fluid
      were lower than serum levels in late follicular phase both in physiologic and in
      FSH-stimulated cycles. CONCLUSION(S): Reduction of IGFBP-3 is an important
      mechanism allowing a larger local availability of free IGFs, which modulate the
      response of follicles to gonadotropin stimulation. This effect is amplified in
      stimulated cycles.

PMID- 9660438
TI  - Reliability of intraobserver and interobserver sonographic endometrial stripe
      thickness measurements.
AB  - OBJECTIVE: To determine the intraobserver and interobserver reliability of
      endometrial stripe thickness measurements in women undergoing controlled ovarian
      hyperstimulation. DESIGN: Prospective blinded study. SETTING: Tertiary care,
      university hospital. PATIENT(S): Sixty-three patients undergoing controlled
      ovarian hyperstimulation and being monitored with transvaginal ultrasound were
      studied. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Intraobserver and
      interobserver variability of endometrial stripe thickness measurements between 2
      blinded observers, with 2 observations made by each observer. RESULT(S): A
      statistically significant correlation was detected between the 2 measurements of
      each observer. The mean (+/-SD) interobserver difference between the average of
      the 2 measurements performed by both observers was 1.02 +/- 0.82 mm. A
      statistically significant correlation between the measurements of the 2 observers
      was detected. For both observers A and B, who used < or =6 mm as an abnormal
      endometrial thickness, an excellent level of agreement was detected between the 2
      measurements made on each patient. When comparing the average values obtained by
      the 2 observers for each of the patients, an excellent level of agreement was
      detected. CONCLUSION(S): There is an excellent correlation between intraobserver
      and interobserver measurements of endometrial stripe thickness.

PMID- 9660437
TI  - A barrier composed of chemically cross-linked hyaluronic acid (Incert) reduces
      postoperative adhesion formation.
AB  - OBJECTIVE: To test whether a barrier of chemically cross-linked pure hyaluronic
      acid reduces postoperative adhesion formation. DESIGN: The material was evaluated
      in the murine uterine horn model using excision and electrocautery injuries and
      in animals who had amounts of material inserted into the abdomen to evaluate
      toxicity. SETTING: Academic medical center. SUBJECT(S): Mice. INTERVENTION(S):
      Insertion of the barrier between uterine horns and into the peritoneal cavity.
      MAIN OUTCOME MEASURE(S): Adhesion formation at 14 days; the histology of the
      peritoneum, liver, and spleen at 42 days; and the number, differential count,
      morphology, and flow cytometry of peritoneal leukocytes 3 days postoperatively.
      RESULT(S): Fewer adhesions were present when excision injuries were separated by
      the barrier (12 of 28 sites [43%] versus 23 of 26 control sites [88%]), whereas
      the number of adhesions was unchanged after electrocautery injuries (14 of 26
      sites [54%] versus 17 of 26 control sites [65%]). The uterine horn sites covered
      by the barrier were histologically indistinguishable from controls. No adverse
      impact on the peritoneum and peritoneal fluid leukocyte population was observed
      with barrier insertion. CONCLUSION(S): The use of a barrier composed of a
      chemically cross-linked hyaluronic acid derivative (Incert, Anika Therapeutics,
      Inc., Woburn, MA) reduced postoperative adhesion formation in this model without
      any adverse impact on the peritoneum and peritoneal leukocyte population. This
      barrier material shows promise in preventing postoperative adhesions and deserves
      clinical evaluation.

PMID- 9660439
TI  - Two- and three-dimensional high-resolution imaging of the human oviduct with
      optical coherence tomography.
AB  - OBJECTIVE: To evaluate the feasibility of optical coherence tomography, a new
      method of micron-scale imaging, for high-resolution assessment of the oviduct.
      Optical coherence tomography is analogous to ultrasound except that it measures
      the backreflection of infrared light rather than acoustical waves. DESIGN: The
      ampulla of a human fallopian tube was imaged in vitro using optical coherence
      tomography. Images were generated in 2 and 3 dimensions. SETTING: University.
      PATIENT(S): Samples were obtained from women who had undergone hysterectomy for
      leiomyomatosis. INTERVENTION(S): None MAIN OUTCOME MEASURE(S): The ability to
      perform imaging on a micron scale, which is a level of resolution higher than
      that of any currently available clinical technology. RESULT(S): Two- and three
      dimensional data sets of the reflectance of a human fallopian tube were acquired.
      A volume of 5 x 5 x 2.5 mm (length x width x depth) was scanned. The axial
      resolution was 11 microm, and the lateral resolution at the focus was 20 microm.
      The data sets showed detailed structures of the fallopian tube. CONCLUSION(S):
      Our ability to obtain micron-scale two- and three-dimensional images of an in
      vitro oviduct suggests that it may be possible to identify and surgically treat
      tubal causes of infertility.

PMID- 9660440
TI  - Heterotopic abdominal pregnancy treated at laparoscopy.
AB  - OBJECTIVE: To report a case of laparoscopic treatment of a heterotopic primary
      abdominal pregnancy after IVF with preservation of the concurrent intrauterine
      pregnancy. DESIGN: Case report. SETTING: University-based IVF program.
      PATIENT(S): A woman with a heterotopic abdominal pregnancy after IVF-ET.
      INTERVENTION(S): Pituitary down-regulation with luteal leuprolide acetate,
      ovulation induction with menotropins, IVF-ET, progesterone in oil for luteal
      support, laparoscopy, and resection of the abdominal gestation. MAIN OUTCOME
      MEASURE(S): Human chorionic gonadotropin levels, pelvic ultrasound examinations,
      and laparoscopic and pathologic findings. RESULT(S): A heterotopic abdominal
      pregnancy occurred after IVF-ET and was treated successfully with laparoscopy.
      The concurrent intrauterine pregnancy was delivered at term. CONCLUSION(S): Early
      diagnosis of an ectopic abdominal pregnancy allowed successful laparoscopic
      treatment, without sequelae to the intrauterine gestation.

PMID- 9660441
TI  - Intraluminal ultrasound imaging of the fallopian tube wall: results of
      standardized in vitro investigations of pig and human tubal specimens.
AB  - OBJECTIVE: To investigate to what extent anatomic structures of the tubal wall
      can be identified reproducibly and whether altered areas can be detected and
      delimited by intraluminal ultrasound. DESIGN: Standardized in vitro experiment
      with descriptive evaluation of findings, comparative analysis of apparative and
      morphologic data, and determination of interobserver variability (video
      documentation, blinded reviewer). SETTING: Department of Gynecology and
      Obstetrics, University of Heidelberg, Germany. SPECIMEN(S): Seventy-two human and
      pig fallopian tubes. INTERVENTION(S): Catheterization with a 2.9F or 3.2F
      ultrasound catheter and sonographic depiction of the fallopian tube, with either
      simultaneous manual and sonographic wall-thickness measurement or coagulation of
      the tubal wall. MAIN OUTCOME MEASURE(S): A correlation coefficient of r = 0.76
      for manual and sonographic tubal wall measurements and K = 0.88 (with 95%
      confidence interval of 0.74-1.0) for interobserver variability in recognizing
      coagulated areas. RESULT(S): Tubal wall anatomy and artificially altered
      (coagulated) areas were displayed reproducibly with intraluminal ultrasound, thus
      giving a characteristic, recognizable pattern of the tubal wall. CONCLUSION(S):
      These in vitro experiments provide evidence that intraluminal ultrasound may
      expand the current diagnostic possibilities in cases of tubal pathology,
      providing nonsurgical access to the tubal wall.

PMID- 9660442
TI  - Comparison of low-technology and high-technology monitoring of clomiphene citrate
      ovulation induction.
AB  - OBJECTIVE: To determine whether newer monitoring techniques, including urinary
      detection of the LH surge and vaginal ultrasound, offer an advantage over basal
      body temperature (BBT) charts alone in achieving pregnancy using clomiphene
      citrate (CC). DESIGN: Randomized clinical trial. SETTING: Infertility patients in
      an academic research environment. PATIENT(S): Forty-five women undergoing
      ovulation induction with CC. INTERVENTION(S): The women were assigned randomly to
      receive either low- or high-technology ovulation monitoring for a total of 3
      ovulatory cycles. Both groups were followed with BBT charts. The high-technology
      group also was monitored with urinary LH kits and vaginal ultrasound. MAIN
      OUTCOME MEASURE(S): Cycle fecundity rates for each technique were compared
      statistically with use of life-table analysis. RESULT(S): Forty-five patients
      were studied during a total of 134 cycles. The overall cycle fecundity rate was
      8%, 10% (8 of 81 cycles) for the low-technology monitoring group and 6% (3 of 53
      cycles) for the high-technology monitoring group. These rates were not
      statistically significant when evaluated by Fisher's exact test (P = .53) or when
      using life-table analysis and a log-rank test (P = .48). CONCLUSION(S): These
      data suggest that, for initial attempts at ovulation induction with CC in
      unselected patients, high-technology monitoring of ovulation offers no increase
      in fecundity over low-technology monitoring.

PMID- 9660443
TI  - Firm oysters year round? Activation of developmental programs in human oocytes.

PMID- 9660444
TI  - Infertility treatment--setting priorities for the future.

PMID- 9660445
TI  - Sensitivity specificity and likelihood ratios--do they deserve confidence
      intervals?

PMID- 9660446
TI  - Percutaneous vasal sperm aspiration and intrauterine insemination.

PMID- 9660447
TI  - A high degree of cross reactivity between the antigens of Taenia solium and
      Taenia crassiceps, potentially useful for the diagnosis of human
      neurocysticercosis (NCC)

PMID- 9660448
TI  - Association of elevated lymph node cell release of histamine and tumor necrosis
      factor with genetic predisposition to limb edema formation in dogs infected with
      Brugia pahangi.
AB  - Brugia pahangi infection in the canine rear limb results in marked lymphatic duct
      and popliteal lymph node pathologic changes. Limb edema is variably associated
      with infection and does not correlate well with duct or node lesions. To
      understand the mechanisms of limb edema, lymph node cells were collected by
      sequential biopsy following infection and examined for production of inflammatory
      mediators. Lymph node cells from a litter of dogs selectively bred with a high
      incidence of edema formation (82%) demonstrated spontaneously released histamine
      and prostaglandin E2 levels higher than those of closely related nonedema-forming
      dogs (0-20%) and/or control dogs. These edema-forming dogs also showed elevated
      release of tumor necrosis factor-alpha when cells were cultured with Brugia
      antigen. Toluidine blue staining of infected lymph node sections revealed that
      the edema-forming dogs had higher numbers of mast cells than infected lymph nodes
      of nonedema-forming dogs.

PMID- 9660449
TI  - Linkage analysis of blood Plasmodium falciparum levels: interest of the 5q31-q33
      chromosome region.
AB  - There is accumulating evidence for the involvement of genetic factors in the
      human response to malaria infection, mostly based on results obtained in studies
      of severe clinical malaria. The role of major gene(s) controlling blood
      parasitemia levels in human malaria has also been detected by means of
      segregation analysis. To confirm and to localize such gene(s), we performed a sib
      pair linkage analysis investigating the role of five candidate chromosomal
      regions: 6p21 (HLA-tumor necrosis factor region), 2q13-q21 (genes coding for
      interleukin-1 alpha and beta), 14q11 (locus coding for the alpha chain of T cell
      antigen receptor), 7q35 (gene cluster for the beta subunit of T cell receptor),
      and 5q31-q33, which includes several candidate genes and was recently linked to a
      locus controlling infection levels by Schistosoma mansoni, denoted as SM1. The
      analysis was carried out on nine families from a southern Cameroon village, and
      the phenotype under study was blood infection levels with Plasmodium falciparum.
      No linkage was found with any of the four markers outside the 5q31-q33 region. A
      trend in favor of linkage was observed in the distal part of the 5q31-q33 region,
      especially with the marker D5S636 (P < 0.05 using the Monte Carlo P value), which
      was the marker that provided the highest evidence for linkage with SM1. These
      results suggest that a locus influencing P. falciparum levels in malaria could be
      located in the same genetic region as that containing SM1, indicating that the
      5q31-q33 region may be critical in the control of different parasite infections.

PMID- 9660450
TI  - Behavior in a mouse model of isolates of Leishmania donovani sensu lato cultured
      from the blood of patients with chronic cutaneous lesions.
AB  - Our objective was to characterize biologically in an animal model two isolates of
      Leishmania parasites unexpectedly encountered in the circulating blood of two
      patients with chronic cutaneous leishmaniasis. Both isolates were classified by
      cellulose acetate electrophoresis as belonging to the L. donovani senso lato
      complex. We elected to use BALB/c mice, an inbred strain that has been proven to
      be very sensitive to the dermotropic parasite L. major. This study demonstrated
      that for the same number of parasites, the course of infection with the L.
      donovani strain was different from that developed in similar animals that
      received the L. major strain. After a protracted incubation period, L. donovani
      produced scanty cutaneous lesions and mainly a systemic disease. This is in
      contrast to the rapidly spreading skin lesion that kills L. major-infected
      animals within a few months. It is concluded that BALB/c mice are an adequate
      animal model for the L. donovani strain, which had an unusual clinical
      presentation in humans. The prolonged incubation period, such as observed here,
      may lead to erroneous conclusions of host resistance if the experiment were
      terminated based on L. major activity in the same model. Finally, the unusual
      behavior in humans and mice of certain strains (such as the one encountered in
      these patients) must reflect peculiar intrinsic features of the parasite, which
      are best understood using animal models in the laboratory.

PMID- 9660451
TI  - Humoral nitric oxide levels and antibody immune response of symptomatic and
      indeterminate Chagas' disease patients to commercial and autochthonous
      Trypanosoma cruzi antigen.
AB  - We report here the evaluation of chagasic patients for the presence and/or
      severity of the disease, antibody to Trypanosoma cruzi, and nitric oxide (NO)
      serum levels. Serum samples tested by ELISA with autochthonous and commercial
      antigen revealed that 10% and 7.5% of the individuals were anti-T. cruzi antibody
      positive, respectively. Ten of 21 seropositive individuals had no clinical signs,
      the other 11 cases presented cardiomyopathy and/or mega-gastrointestinal
      syndromes, and three patients presented a combined form. A statistical difference
      (P < 0.001) in antibody titer between asymptomatic and symptomatic patients with
      autochthonous antigen was detected, and serum NO levels was found to be three
      times higher in cases than in controls. These results suggest that it is
      recommended to use a sole source of antigen (autochthonous) for the serodiagnosis
      of Chagas' disease, and that the pathogenic role of NO in this disease should be
      evaluated.

PMID- 9660452
TI  - Clinicopathologic characteristics of the lungs of patients with human T cell
      lymphotropic virus type 1-associated myelopathy.
AB  - Lung autopsy specimens were evaluated histologically in the six patients with
      human T cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy (HAM). The
      results revealed two histologic changes. First, lymphoid infiltrates were
      distributed widely in peribronchiolar and perivascular regions, subpleural
      regions, and the alveolus. Lymphoid infiltrates were also observed in bronchial
      mucosal glands in relatively large bronchi, in which the acinar epithelium was
      sometimes degenerated. Second, chronic inflammatory changes, such as smooth
      muscle hypertrophy, fibrosis, or squamous cell metaplasia, were increased
      significantly in the membranous bronchioles of HAM patients compared with
      specimens from lung cancer control patients. Such histologic changes were
      subclinical in most cases, but one case had an abnormal chest shadow, and two
      cases had recurrent pneumonia. In HAM patients, high levels of HTLV-1-specific
      cytotoxic T lymphocytes are believed to attack the HTLV-1-bearing cells in the
      lung, resulting in inflammatory reactions.

PMID- 9660453
TI  - Surveillance for Ross River virus infection using blood donors.
AB  - The number of clinical Ross River virus (RRV) infections (epidemic polyarthritis)
      each year in Australia continues to grow despite extensive vector control
      programs. There is a need, therefore, for a surveillance program that can give
      sufficient warning of outbreaks of the disease so that highly focused
      preventative measures may be undertaken. The ability of a surveillance program,
      based on voluntary Red Cross blood donations, to predict outbreaks of epidemic
      polyarthritis was evaluated. Anti-RRV IgM antibody was detected in significant
      numbers of blood donors from throughout the state of Queensland 6-9 weeks prior
      to an increase in the number of notified cases of epidemic polyarthritis. At a
      local level, significant numbers of anti-RRV IgM blood donors were detected in
      Brisbane in 1996 four weeks prior to an increase in the number of notified cases
      of epidemic polyarthritis. This system of surveillance is technically simple,
      rapid (results are obtained in 2-3 days), it samples the human population from
      throughout the state, and it gives timely warning of outbreaks of epidemic
      polyarthritis.

PMID- 9660454
TI  - Seroprevalence of hepatitis E virus among United Nations Mission in Haiti (UNMIH)
      peacekeepers, 1995.
AB  - Information about the prevalence of hepatitis E virus (HEV) infection is sparse
      in many countries. Following the identification of four cases of acute HEV
      infection among Bangladeshi soldiers, a serologic survey was conducted to
      determine the prevalence of HEV infection among other peacekeepers from the
      United Nations Mission in Haiti (UNMIH) and Haitian civilians. Of the 981
      participants in the survey, 876 were soldiers from eight UNMIH-participating
      countries representing Asia, Africa, and the Americas, and 105 were Haitian
      civilians. The prevalence of HEV infection by country (from highest to lowest)
      included Pakistan (62%), India (37%), Nepal (37%), Bangladesh (27%), Djibouti
      (13%), Honduras (6%), Guatemala (5%), Haiti (3%), and the United States (2%).
      More than 90% of those surveyed from Guatemala, Haiti, and Honduras, where
      prevalence data has been scarce, appeared susceptible to HEV infection. Future
      multinational missions like the UNMIH might also present unique opportunities to
      study health threats of widespread interest.

PMID- 9660455
TI  - Short report: Decrease in seroprevalence of antibodies to hantavirus in rodents
      from 1993-1994 hantavirus pulmonary syndrome case sites.
AB  - Rodent trapping was conducted at seven hantavirus pulmonary syndrome (HPS) case
      sites from June 1993 to March 1994 during the HPS outbreak in the southwestern
      United States. To determine if there were changes in the rodent population or the
      hantavirus seroprevalence in rodents since the HPS outbreak, rodents were trapped
      at the same sites three years later using the same trapping protocol. The trap
      success decreased from the numbers trapped during the outbreak, however, the
      number of Peromyscus, as a percentage of the total rodents captured, did not
      noticeably decrease. In addition, the seroprevalence of hantavirus antibodies in
      Peromyscus decreased significantly (P < 0.0001).

PMID- 9660456
TI  - Diversity of Babesia infecting deer ticks (Ixodes dammini).
AB  - To determine whether the presence of nonpathogenic piroplasms may confound field
      estimates of risk of Babesia microti infection, we identified sporozoites
      infecting the salivary glands of deer ticks (Ixodes dammini) by parallel
      microscopy and polymerase chain reaction assays. Piroplasms were evident in 14.4%
      of adult ticks from sites in the northcentral and northeastern United States. Of
      these, 83.3% contained DNA characteristic of Ba. odocoilei. This cervid piroplasm
      was detected in all of the sites examined and generally was more prevalent than
      was Ba. microti. Because deer ticks transmit both Ba. odocoilei and Ba. microti,
      estimates of pathogen prevalence based solely on microscopy may overestimate the
      risk of human babesiosis.

PMID- 9660457
TI  - An interstate outbreak of tick-borne relapsing fever among vacationers at a Rocky
      Mountain cabin.
AB  - In July 1995, an outbreak of acute febrile illness affected 11 (48%) of 23 family
      members from Nebraska and Kansas who had vacationed at a Colorado cabin in June.
      Similar symptoms were identified among five (17%) of 30 additional persons from
      Nebraska, Kansas, Florida, and Texas who had vacationed at the same cabin.
      Symptoms suggested tick-borne relapsing fever (TBRF). Although no spirochetes
      were detected in available blood smears from five case-patients, Borrelia hermsii
      was cultured from the blood of one case-patient and two chipmunks trapped near
      the cabin. Case-patients were more likely than non-ill cabin visitors to have
      slept on the floor (odds ratio [OR] = 28.0, 95% confidence interval [CI] = 3.0
      258) or in the top bunk bed (OR = 5.2, 95% CI = 1.1-25.1). Tick-borne relapsing
      fever should considered in the differential diagnosis of fever in patients who
      have stayed overnight in mountain cabins in the western United States.

PMID- 9660458
TI  - Influence of humans and domestic animals on the household prevalence of
      Trypanosoma cruzi in Triatoma infestans populations in northwest Argentina.
AB  - In three rural villages of northwest Argentina, the overall proportion of
      domiciliary Triatoma infestans infected with Trypanosoma cruzi was 49% among
      1,316 bugs individually examined for infection in March and October 1992). Most
      of the variation among individual households in the proportion of infected
      triatomines was explained by variations among houses in the proportion of bugs
      that fed on dogs or cats, the prevalence of infected dogs or cats, and the
      proportion of bugs that fed on humans, according to a logistic multiple
      regression analysis. The effects of human infection rates on bug infection rates
      were not statistically significant. After adjusting for the effects of other
      predictors, the presence of chickens in bedroom areas had negative and
      significant effects on the proportion of infected Triatoma infestans, and
      positive and significant effects on the number of T. cruzi-infected triatomines
      collected per person-hr per house. Dog or cat infection rates and the proportion
      of bugs that fed on dogs or cats and on chickens explained 80% of the total
      variance of infected-bug numbers in a linear multiple regression model. This is
      the first study to use detailed field data to show that variations in triatomine
      infection rates depend on bug host feeding patterns and dog or cat infection
      rates, while the presence of chickens in bedroom areas exerts opposite effects on
      the proportion and number of infected triatomines. Domestic animals play a
      crucial role in the domiciliary transmission of T. cruzi.

PMID- 9660459
TI  - Neurocysticercosis in Ceara State, northeastern Brazil: a review of 119 cases.
AB  - Relatively little is known about the occurrence of neurocysticercosis in
      northeastern Brazil. There have been no published reports from the state of
      Ceara, but a review of the records at the Hospital Sao Jose in Fortaleza, Brazil
      identified 119 patients with neurocysticercosis diagnosed between January 1988
      and April 1994. Patients came from 43 municipalities in Ceara. Their ages ranged
      from five to 74 years; the greatest number of cases were in persons 10-40 years
      of age; 63% were males. Seizures were the presenting complaint in 64% of the
      patients and headache in 22%. Two patients, each with several hundred
      intracranial lesions, presented with mental status changes; one was initially
      given the clinical diagnosis of viral meningoencephalitis. Computed tomography
      scans showed that 44% of the patients had five or more lesions. Cysts were found
      throughout the brain. The parietal lobe was the most frequent site of
      involvement; 85% of patients had one or more lesions there. The brain stem was
      involved in 8%. There was no consistent association between the severity of the
      clinical abnormalities and the radiologic findings. Computed tomography of the
      thighs was done in 10 persons; cysts were identified in nine.

PMID- 9660462
TI  - Lytic antibodies in Trypanosoma cruzi-infected persons with low parasitemia.
AB  - An antibody-dependent, complement-mediated lysis test performed with three
      Chilean trypomastigote strains used as target cells revealed strain dependence in
      the detection of lytic antibodies in chronic chagasic sera. The highest
      percentage of lytic sera was observed when MF or V115 strains were used as target
      cells (90% and 71%, respectively) in the chronic chagasic group with negative
      xenodiagnosis results. No significant statistical association was observed
      between lytic activity in chronic chagasic sera and the presence or absence of
      cardiopathy (P > 0.01). Western blot analysis showed that lytic sera recognize
      different antigens depending on the strain used and nonlytic sera had a weaker
      capacity to detect them.

PMID- 9660460
TI  - A target for intervention in Plasmodium falciparum infections.
AB  - We present a set of simple mathematical models to investigate interactions
      between malaria parasites and the human immune system and the differentiation of
      parasites from asexual, pathogenic into sexual, transmissible blood stages. Each
      model represents a different combination of empirically based hypotheses, and
      salient behaviors of each fit criteria developed from clinical data. In all
      models, however, higher gametocyte conversion rates result in lower peak asexual
      form densities. Therefore, to the extent that asexual-form densities are
      associated with disease symptoms, interventions that stimulate gametocytogenesis
      should produce unexpected clinical benefits.

PMID- 9660461
TI  - Immune response and lack of immune response to Plasmodium falciparum P126 antigen
      and its amino-terminal repeat in malaria-infected humans.
AB  - A parasitophorous vacuole protein of Plasmodium falciparum, p126, is a potential
      candidate for a malaria vaccine. Its N-terminal region, composed of six repeats
      of eight amino acids, appears to be involved in the induction of protective
      immunity against P. falciparum challenge in monkeys. This study evaluated the
      immune response to p126 and to its N-terminal region (Nt47) in patients (n = 45)
      living in a malaria-endemic area of Brazil (Colina, Porto Velho, Rondonia).
      Cellular proliferative responses against Nt47 were low and infrequent. The study
      of the humoral immune response demonstrated that 95% of the patients had
      detectable anti-p126 antibodies and 77% had anti-Nt47 antibodies. Analysis of the
      antibody isotypes specific for Nt47 revealed that all four IgG subclasses were
      present and individuals with higher levels of anti-Nt47 cytophilic IgG antibody
      (IgG1 + IgG3/IgG2 + IgG4) had significantly lower parasitemia levels, suggesting
      that antibodies to the N-terminal region of the p126 protein may contribute to
      acquisition of immunity to P. falciparum malaria.

PMID- 9660463
TI  - Prevention of Borrelia burgdorferi transmission in guinea pigs by tick immunity.
AB  - We examined the effect of repeated infestation of guinea pigs with Ixodes
      scapularis on the capacity of ticks to transmit Borrelia burgdorferi infection.
      Repeated challenges with nymphs or larvae lead to a reduction in duration of
      nymphal tick attachment and weight of recovered ticks consistent with the
      development of tick immunity. Only one of 18 I. scapularis-immune guinea pigs
      challenged with B. burgdorferi-infected nymphal ticks became infected, whereas 10
      of 18 naive guinea pigs similarly challenged became infected. We conclude that
      tick immunity interferes with borrelial transmission.

PMID- 9660464
TI  - Laboratory evaluation of a dot-blot enzyme immunoassay for serologic confirmation
      of illness due to Rickettsia conorii.
AB  - Of the 169 United States Army soldiers who deployed on a field training exercise
      to a remote area of Botswana for two weeks in January 1992, more than 30%
      developed a febrile illness within five days of their return. A diagnosis of
      South African tick typhus was suggested by soldiers' exposure to ticks, as well
      as the presence of eschars and vesicles at the site of tick bites, and tender
      regional lymphadenopathies. This high attack rate, experienced during such a
      short exposure period, emphasizes the hazard of illness due to Rickettsia conorii
      to persons visiting endemic areas. A rapid, diagnostic, semiquantitative enzyme
      immunoassay (DS) for detection of IgG and IgM antibodies to R. conorii was
      performed on 209 acute and convalescent sera from soldiers in the outbreak and on
      75 control sera. For the acute sera from soldiers meeting the probable case
      definition of having both regional lymphadenopathy and tick bite eschar, as
      judged by an IgG indirect fluorescent antibody (IFA) test, the resulting
      sensitivity and specificity of the DS test were 100% and 48%, respectively. In
      the analysis of the acute sera, the DS test identified as reactive more of the
      probable cases (62%) than either the IgG (16%) or IgM (55%) IFAs. This simple and
      rapid diagnostic test could be useful in establishing a preliminary diagnosis of
      R. conorii rickettsiosis in remote settings when immediate confirmation by IFA is
      impossible.

PMID- 9660465
TI  - Short report: An imported case of cystic echinococcosis in Japan diagnosed by
      imaging and serology with confirmation of Echinococcus granulosus-specific DNA
      sequences.
AB  - We report one case of cystic echinococcosis (CE) in Japan in a native of Nepal.
      Ultrasonography and computed tomography scan of the liver revealed unique cystic
      lesions with or without daughter cysts of Echinococcus granulosus. Immunoblot
      analysis using crude antigens of E. multilocularis and cyst fluid of E.
      granulosus, without reference to these image analyses, strongly suggested this
      was a case of CE. We found protoscoleces in surgically removed hepatic lesions
      and analyzed the mitochondrial cytochrome c oxidase subunit I (COI) gene by the
      polymerase chain reaction. Based on the similarity in DNA sequences of the COI
      gene of this Echinococcus spp. with that of previously reported sheep-dog strain
      (GI), the parasite was considered to be the so-called common sheep strain of E.
      granulosus.

PMID- 9660466
TI  - Short- and long-term efficacy of single-dose subunit vaccines against Yersinia
      pestis in mice.
AB  - A single, subcutaneous, 30-microg dose of either a combination of the Yersinia
      pestis proteins F1+V or a F1-V fusion protein adsorbed to the adjuvant aluminum
      hydroxide, protected Hsd:ND4 mice for one year against pneumonic plague. The
      recombinant F1+V vaccine provided significant protection as early as day 14
      postimmunization. The current Plague Vaccine USP in a single 0.2-ml dose did not
      provide significant protection in this mouse model. Antibody titers to F1 and V
      peaked at approximately 5-12 weeks postimmunization and were still detectable one
      year later. These F1 and V subunit vaccines may offer effective long-term
      immunity with a reduced dosage schedule when compared with the presently
      licensed, formalin-killed, whole-cell vaccine.

PMID- 9660467
TI  - Occurrence and susceptibility to antibiotics of Shigella species in stools of
      hospitalized children with bloody diarrhea in Pakistan.
AB  - The aim of the present investigation was to study the frequency of Shigella spp.
      in patients with bloody diarrhea in Pakistan and the susceptibility of isolated
      Shigella to three antibiotics: ampicillin, cotrimoxazole and nalidixic acid. In
      addition, the frequency of Campylobacter and Salmonella was also determined.
      Stool samples (n = 152) were collected from 152 diarrheic children less than six
      years of age passing blood and mucus in their stools who were admitted to
      Paediatric Department of Mayo Hospital in Lahore, Pakistan from June to September
      1990. The samples were cultivated on standard media for Shigella, Campylobacter,
      and Salmonella. Susceptibility of Shigella isolates was tested by disk diffusion
      method. The frequency of isolation was 19.1% for Shigella spp., 7.9% for
      Campylobacter, and 4.6% for Salmonella. Shigella flexneri (7.9%) was the most
      frequently isolated species, followed by S. dysenteriae (6.6%), S. boydii, (3.3%)
      and S. sonnei (1.3%). All Shigella isolates were susceptible to nalidixic acid
      (100%), while only a few were susceptible to cotrimoxazole (7.0%) and ampicillin
      (3.5%). In Pakistan, self-medication and purchases of drugs without a
      prescription are commonly practiced. Thus, there is a greater possibility of
      development of resistant strains due to over use of antibiotics.

PMID- 9660468
TI  - Activity of anticancer compounds against Trypanosoma cruzi-infected mice.
AB  - Chagas' disease, which is caused by Trypanosoma cruzi, remains essentially
      incurable. Due principally to a lack of profit incentive, the pharmaceutical
      industry has had limited interest in developing new antichagasic drugs. Thus, a
      search for agents that exhibit activity against T. cruzi, although medicaments
      have been developed for the treatment of other diseases, seems justifiable.
      Responding to evidence that the principal biochemical differences between
      mammalian cells and African trypanosomes apply equally to T. cruzi, our
      evaluations were conducted. Previous work showed the effectiveness of anticancer
      agents against T. rhodesiense. In the present studies, 76 anticancer compounds
      were assessed for their ability to suppress the trypomastigotes of T. cruzi-
      infected mice. Five compounds were found to be active. The most effective was
      cycloheximide, which was more than six times as effective as the standard,
      nifurtimox.

PMID- 9660469
TI  - Brazilian isolates of Trypanosoma cruzi from humans and triatomines classified
      into two lineages using mini-exon and ribosomal RNA sequences.
AB  - Traditional molecular and biochemical methods, such as schizodeme analysis,
      karyotyping, DNA fingerprinting, and enzyme electrophoretic profiles, have shown
      a large variability among Trypanosoma cruzi isolates. In contrast to those
      results, polymerase chain reaction (PCR) amplification of sequences from the 24S
      alpha ribosomal RNA gene and from the mini-exon gene nontranscribed spacer
      indicated a dimorphism among T. cruzi isolates, which enabled the definition of
      two major parasite lineages. In the present study, 86 T. cruzi field stocks (68
      isolated from humans with defined presentations of Chagas' disease and 18 from
      triatomines) derived from four Brazilian geographic areas were typed by the PCR
      assay based on the DNA sequences of the mini-exon and 24S alpha rRNA genes. These
      stocks were ordered into the two major T. cruzi lineages. Lineage 1 was
      associated mainly with human isolates and lineage 2 with the sylvatic cycle of
      the parasite.

PMID- 9660470
TI  - A single tissue culture system for the propagation of the agents of the human
      ehrlichioses.
AB  - Two newly emergent human diseases found in the United States, human
      monocytotropic ehrlichiosis (HME) and human granulocytotropic ehrlichiosis (HGE),
      are caused by pathogens of the genus Ehrlichia. The causative agent of HGE can be
      propagated in HL-60 human promyelocytic leukemia cells. Herein, we report the
      development of a method to propagate E. chaffeensis, the causative agent of HME,
      in HL-60 cells, thus providing a common system for the study of both species. The
      continuous propagation of E. chaffeensis requires the induction of HL-60
      differentiation along the monocytic pathway toward phenotypically mature
      macrophages by the addition of 25-OH vitamin D3 to the growth medium.

PMID- 9660471
TI  - Detection of the filarial parasite Mansonella streptocerca in skin biopsies by a
      nested polymerase chain reaction-based assay.
AB  - To differentiate the skin-dwelling filariae Mansonella streptocerca and
      Onchocerca volvulus, a nested polymerase chain reaction (PCR) assay was developed
      from small amounts of parasite material present in skin biopsies. One nonspecific
      and one specific pair of primers were used to amplify the 5S rDNA spacer region
      of M. streptocerca. Biopsies with different microfilaria densities obtained from
      104 Ugandans living in an area endemic for M. streptocerca were tested using both
      the nested PCR assay and standard parasitologic assessment of microfilariae. All
      82 samples from microfilaria carriers were positive when tested using the nested
      PCR assay. In addition, M. streptocerca DNA could be detected in 16 samples
      thought to be microfilaria negative. Furthermore, six days following ivermectin
      treatment, M. streptocerca DNA was found in 12 of 14 microfilaria-negative
      biopsies. Control skin samples from patients infected with O. volvulus were all
      negative in the nested PCR assay. This assay improves the diagnosis of M.
      streptocerca and will facilitate further epidemiologic studies.

PMID- 9660472
TI  - Excessive fibrinolysis: the coagulopathy following Merrem's hump-nosed viper
      (Hypnale hypnale) bites.
AB  - In 56 patients with proven hump-nosed viper (Hypnale hypnale) bites, 12 (21.4%)
      developed continued oozing of blood from the site of the bite and a prolonged
      clotting time. Further investigations showed low fibrinogen levels and increased
      fibrinogen degradation products in plamsa. The bleeding time, platelet count,
      prothrombin time, and partial thromboplastin time with kaolin were normal. The
      bite of this snake can be complicated with a coagulopathy in which excessive
      fibrinolysis seems to be the main abnormality.

PMID- 9660473
TI  - Cutaneous scars in American tegumentary leishmaniasis patients: a site of
      Leishmania (Viannia) braziliensis persistence and viability eleven years after
      antimonial therapy and clinical cure.
AB  - Two former patients treated for the cutaneous form of American tegumentary
      leishmaniasis were reviewed eight and 11 years, respectively, following clinical
      cure. We were able to isolate Leishmania parasites in a culture of material from
      the two scar biopsies, and in one of them the parasite was characterized as
      Leishmania (Viannia) braziliensis. In both cases, the histopathology revealed
      discreet hyperceratosis and a slight infiltrate of mononuclear cells surrounding
      and on the walls of the surface and deep dermal vessels. No amastigotes were seen
      on immunohistochemical or histopathologic examination. The Montenegro skin test
      result and the in vitro lymphoproliferative response to Leishmania antigen were
      positive, but no specific IgG and IgM antibodies were detected.
      Otorhinolaryngologic examination showed no macroscopic alteration in the mucosae.
      These findings are important for the evaluation and criteria of post-treatment
      cure.

PMID- 9660474
TI  - Evaluation of N,N-diethyl-m-toluamide (DEET) as a topical agent for preventing
      skin penetration by cercariae of Schistosoma mansoni.
AB  - The effect of skin application of N,N-diethyl-m-toluamide (DEET) on the
      penetration and migration behavior of cercariae of Schistosoma mansoni was
      evaluated in vitro and in vivo in a mouse model. These studies showed that DEET
      at concentrations of 7.5% or higher was 100% effective in immobilizing and
      killing cercariae of S. mansoni in vitro. Ultrastructural studies on such DEET
      exposed cercariae showed transformative and degenerative changes involving both
      tegument and deeper parenchymal structures. Fatal tissue lesions were evident as
      early as 5 min postexposure to DEET, and became more extensive with increasing
      exposure time. Cutaneous application of DEET (as a pure chemical in isopropanol
      or as a commercial insect repellent preparation) was more than 99% effective in
      preventing entry of S. mansoni cercariae into the mouse tail skin. Radiolabeling
      and tracer studies confirmed that 7.5% DEET applied to the skin prior to
      infection was highly effective in preventing schistosomular migration to the
      lungs.

PMID- 9660476
TI  - "Gold standards" for vision testing.

PMID- 9660475
TI  - Field evaluation of a dog owner, participation-based, bait delivery system for
      the oral immunization of dogs against rabies in Tunisia.
AB  - We evaluated a dog owner, participation-based, bait delivery system for the oral
      immunization of dogs against rabies. In a field study in a semirural area of
      northern Tunisia, dog owners were asked to come to temporary bait delivery sites.
      A total of 314 baits were given to 178 dog owners in four sites. The experimental
      baits used consisted of a freeze-dried core unit containing sulfadimethoxine
      (SDM) as a biological marker and an aromatized paraffin envelope. No vaccine was
      used. Preliminary tests had shown that by using a rapid commercial card test,
      positive SDM serum levels were detected in more than 95% of dogs up to two days
      after bait ingestion. During the two days following bait delivery, we visited
      more than 95% of all households in the study area and took blood samples from as
      many owned dogs as possible. Unconsumed baits were recovered and human contacts
      with the bait matrix were recorded. The campaign required 7.6 person-min per bait
      and 13.5 person-min per dog owner for providing baits, gloves, and instructions.
      The estimated average cost effectiveness ratio per dog accepting a bait was 1.7
      US dollars. From the indications given by the dog owners and the results of the
      SDM test, it was concluded that 85-90% of the owned dogs in the study area had
      consumed a bait at least partially. Of 314 baits delivered, 78.7% were fully
      consumed by dogs and 4.1% were recovered during the household survey. The
      remaining baits (17.2%) that were not recovered were either not consumed or only
      partially consumed by the target dogs (3.7 baits per 100 inhabitants). These
      baits probably remained within the highly populated areas and were potentially
      accessible to other domestic animals and other nontarget species, including
      humans. Twenty-five unprotected human contacts with baits were recorded (1.7% of
      all inhabitants). Our study has demonstrated the potential of dog owner based
      bait delivery. This technique is simple and efficient, particularly if the human
      population is accustomed to mass immunization in defined centers. Before applying
      this method on a large scale with live vaccine loaded baits, further studies
      should focus on minimizing the number of human contacts with the vaccine bait,
      systematizing contact identification and establishing structures in ensuring
      proper treatment if exposure to vaccine should occur.

PMID- 9660477
TI  - Induction of apoptosis in human retinoblastoma cells by topoisomerase inhibitors.
AB  - PURPOSE: To examine the apoptotic effect induced in human retinoblastoma Y79
      cells by camptothecin, etoposide, and amsacrine, to examine the effect of these
      drugs on the expression of many apoptosis-related modulators, and to test the
      antiapoptotic effect exerted by insulin-like growth factor-I (IGF-I). METHODS:
      Morphologic features of apoptosis were demonstrated using acridine orange-
      ethidium bromide staining and electron microscopy. DNA fragmentation was
      determined by means of an in situ cell detection procedure (TdT-dUTP terminal
      nick-end labeling [TUNEL]) or by electrophoresis on agarose gels and was
      quantified by enzyme-linked immunosorbent assay. The expression of apoptosis
      related modulators was studied by western blot analysis. The processing of latent
      p53 was examined by means of pulse- chase analysis. RESULTS: Camptothecin,
      etoposide, and amsacrine induced apoptosis in Y79 cells in a dose-dependent
      manner; camptothecin was the most efficacious compound. The effect, which was
      dependent on macromolecular synthesis, appeared after a lag of 8 hours and
      increased for as long as 24 hours. It was lower in cells treated with IGF-I, a
      potent mitogenic factor. Camptothecin and etoposide increased the p53 level after
      4 hours of treatment, before the onset of apoptosis. This effect seemed to be a
      consequence of the conversion of latent p53 to one that is transcriptionally
      active. The drugs also induced an increase in p53-related proteins, such as p21,
      Bax, and IGF binding protein-3 (IGF-BP3), and caused a significant reduction of
      the Bcl-2 level. The latter effect was less evident in cells pretreated with IGF
      I. CONCLUSIONS: Topoisomerase inhibitors induce apoptosis in Y79 cells. This
      event is accompanied by a decrease in the expression of Bcl-2, a death
      antagonist, and an increase in that of Bax, a death agonist. A probable
      consequence of these modifications is the activation of ICE-like activity with
      degradation of poly-(adenosine diphosphate [ADP] ribose)-polymerase. Insulin-like
      growth factor-I exerts an antiapoptotic action in Y79 cells, and this function is
      most likely reduced by the overexpression of IGF-BP3 that is induced by drug
      treatment.

PMID- 9660478
TI  - Colocalization of 11-cis retinyl esters and retinyl ester hydrolase activity in
      retinal pigment epithelium plasma membrane.
AB  - PURPOSE: To identify the subcellular locale of 11-cis retinyl esters in bovine
      retinal pigment epithelium (RPE) and to characterize the enzymic mechanism
      responsible for liberation of 11-cis retinoids in this compartment. METHODS:
      Endoplasmic reticulum (ER)- enriched and plasma membrane (PM)-enriched protein
      fractions were prepared from bovine RPE microsomes using sequential discontinuous
      sucrose and Percoll gradient fractionation. Enzyme markers for ER (such as
      carboxylesterase), and PM (such as 5'-nucleotidase [5'-ND]; alkaline phosphatase
      [AP]; and ouabain-sensitive Na+,K+-ATPase [ATPase]) were used to identify the
      subfractions. Membrane-associated retinoids were quantified by high-performance
      liquid chromatography (HPLC) and retinyl ester hydrolase (REH) activities were
      determined by radiometric and chromatographic (HPLC) means. RESULTS:
      Chromatographic analyses of membrane-associated retinoids showed that 11-cis
      retinyl esters are localized mainly in PM-enriched fractions, whereas all-trans
      retinyl esters are associated predominantly with ER-enriched membranes; profiles
      of the distribution of 11-cis- and all-trans REH activities were consistent with
      the retinyl ester distribution. Further purification of the crude PM fraction
      yielded a fraction (P2) that was significantly enriched with 5'-ND (fivefold),
      ATPase (15-fold), AP (10-fold), and 11-cis retinyl ester hydrolase (11-cis REH;
      threefold) activities, but was relatively devoid of carboxylesterase and all
      trans REH activities. Apparent kinetic constants (Km(app) and Vm(app)) for 11-cis
      REH activity in P2 were 18 microM and 1800 picomoles/min per mg, respectively.
      CONCLUSIONS: This is the first identification of an 11-cis-specific REH activity
      in RPE plasma membrane. Results from these studies demonstrate the capacity of
      RPE plasma membranes to accommodate and hydrolyze 11-cis retinyl esters. Plasma
      membrane storage and mobilization of 11-cis retinyl esters represents a novel
      compartmentalization of retinoid metabolism that is distinct from the sites where
      11-cis retinoids are produced. The implication of these findings for present
      theories of visual chromophore biosynthesis are discussed.

PMID- 9660479
TI  - Functional gap junctions in corneal fibroblasts and myofibroblasts.
AB  - PURPOSE: Within the corneal stroma, keratocytes communicate through gap
      junctions. These plasma membrane channels, which connect the cytoplasm of
      adjacent cells, are composed of connexins. In a cell culture model, an
      investigation was conducted to determine whether connexin-based gap junction
      intercellular communication is present in fibroblasts and myofibroblasts, both of
      which replace keratocytes after wounding. METHODS: Fibroblasts and myofibroblasts
      were grown according to preestablished methods. Phenotype was determined by
      immunocytochemistry. A gap junction-permeant dye, Lucifer yellow or Cascade blue,
      and nonpermeant 10-kDa Texas red-dextran were used. Tracer fluorescent dyes were
      introduced by scrape-loading or by microinjection, and their diffusion into
      adjacent cells was recorded photographically. Inhibition of gap junction dye
      transfer was elicited by treatment with 18-alpha-glycyrrhetinic acid (AGA).
      RESULTS: In confluent fibroblast or myofibroblast cultures, the scrape-loaded
      dextran probe remained within wounded cells, whereas the Lucifer yellow or
      Cascade blue dye diffused into adjacent intact cells. Similarly, in nonconfluent
      fibroblast and myofibroblast cultures, microinjected Lucifer yellow rapidly
      diffused from the microinjected cell to adjacent cells. Treatment with 2 microM
      AGA, an uncoupling agent, blocked the spread of Lucifer yellow in fibroblast and
      myofibroblast cultures. CONCLUSIONS: Cultured fibroblasts and myofibroblasts have
      functional gap junctions as has previously been demonstrated for keratocytes in
      vivo. Thus, fibroblasts and myofibroblasts have the ability to establish and
      maintain intercellular communication with themselves and with nonactivated
      keratocytes. This property may be critical in the wound-healing process,
      especially in the avascular corneal environment.

PMID- 9660480
TI  - Signaling by HGF and KGF in corneal epithelial cells: Ras/MAP kinase and Jak-STAT
      pathways.
AB  - PURPOSE: To characterize the signaling pathways used by hepatocyte growth factor
      (HGF) and keratinocyte growth factor (KGF) in human corneal epithelial cells.
      METHODS: Cultures of SV40 large T antigen-transfected human corneal epithelial
      cells were treated with recombinant human HGF or KGF at 50 ng/ml to 100 ng/ml for
      5 to 30 minutes and harvested for protein isolation. Immunoprecipitation was
      performed with antisera to signal transducers and activators of transcription 1
      (STAT1), STAT3, Janus kinase 1 (Jak1), Shc, Grb2, Sos1, and HGF receptor (met).
      Immunoprecipitated proteins were analyzed by western blot analysis. Gel
      retardation experiments were carried out with first-passage human corneal
      epithelial cells to detect binding of STATs to the high affinity c-sis (platelet
      derived growth factor) inducible DNA element (hSIE). Effects of HGF, KGF, and
      kinase inhibitors on mitogen-activated protein kinase (MAPK) activation were
      evaluated by western blot analysis and enzymatic assays. RESULTS: In human
      corneal epithelial cells, the phosphorylation of adapter protein Shc (52- and 66
      kDa isoforms) was enhanced by HGF, but not by KGF. Phosphorylated HGF receptor
      coimmunoprecipitated with Shc, Grb2, and Sos1. Hepatocyte growth factor or KGF
      rapidly activated MAPK in corneal epithelial cells. The activation of MAPK (p42
      and p44) by HGF or KGF was transient and decreased gradually within 1 hour. MAPK
      kinase 1 (MEK1) inhibitor PD098059 or the protein tyrosine kinase inhibitor
      genistein blocked MAPK activation. Activation of MAPK induced by HGF was
      partially inhibited by protein kinase C inhibitor calphostin C. Hepatocyte growth
      factor and KGF had no effect on the activation of Jak-STAT cascade components
      that are activated by epidermal growth factor. CONCLUSIONS: Hepatocyte growth
      factor and KGF activate Ras-MAPK pathways in human corneal epithelial cells.
      There may be at least two routes used by HGF in transmitting signals from its
      receptor to the MAPK cascade. One is the receptor-Grb2/Sos complex to the Ras
      pathway, and the other is through protein kinase C. Hepatocyte growth factor and
      KGF did not activate the Jak-STAT cascade components STAT1, STAT3, or Jak1 in
      corneal epithelial cells.

PMID- 9660481
TI  - Gi2 and Gi3 couple met-enkephalin to inhibition of lacrimal secretion.
AB  - PURPOSE: The intent of this study was to identify the pertussis toxin-sensitive G
      proteins that couple met-enkephalin to the inhibition of cholinergically
      stimulated secretion in rabbit lacrimal gland acini. METHODS: The authors
      detected G proteins in membranes from freshly isolated glands, freshly isolated
      acini, and cultured lacrimal acini from rabbits by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and immunoblotting. Antibodies against the
      alpha subunits of Gi1, Gi1 and Gi2, or Gi3 were used in cultured acini
      permeabilized by streptolysin-O to determine the role of the G proteins in met
      enkephalin inhibition of cholinergic stimulation of lacrimal acinar protein
      release. RESULTS: Western blot analysis showed the presence of the alpha subunits
      of Gi2 and Gi3, but not Gi1, in all three membrane preparations. The met
      enkephalin analog D-Ala2-methionine enkephalinamide (DALA) inhibited cholinergic
      stimulation of secretion by cultured rabbit acinar cells to near basal levels.
      Inhibition of secretion by DALA was blocked by insertion of antibody to a peptide
      sequence common to Gialpha1 and Gialpha2, but was not blocked by antibody against
      a specific Gialpha1 sequence. The inhibitory effect of DALA also was blocked by
      antibody to a Gialpha3 sequence. At low doses of anti-Gialpha1/2 and anti
      Gialpha3 in combination, the effect on reversal of inhibition was additive.
      However, at higher doses, the effect of the combination was no greater than the
      effect of either antibody alone. CONCLUSIONS: These results demonstrate that met
      enkephalin inhibition of cholinergic secretion is mediated by way of the
      pertussis toxin-sensitive G proteins Gi2 and Gi3 in cultured rabbit lacrimal
      acini. Because the effects of the G proteins are not additive, the intracellular
      events distal to G protein activation most likely converge at some point before
      exocytosis.

PMID- 9660482
TI  - Reoxygenation injury in a cultured corneal epithelial cell line protected by the
      uptake of lactoferrin.
AB  - PURPOSE: To investigate whether reoxygenation after extended hypoxia causes
      cellular damage in cultured corneal epithelial cells and to demonstrate the
      protective effects of lactoferrin. METHODS: Immortalized human corneal epithelial
      cells (T-HCECs) were cultured to confluence in 96-well culture plates, subjected
      to stringent hypoxia (1% O2, 5% CO2, 94% N2 at 37 degrees C) for 24 hours, and
      returned to normoxic conditions (5% CO2, 95% air at 37 degrees C). Cell viability
      was observed by 1 microM propidium iodide staining 0, 2, 4, and 6 hours after
      reoxygenation. Inhibition studies were performed after 2 hours' reoxygenation,
      using 2 mM iron chelator desferrioxamine and 0.2 mg/ml lactoferrin. Confocal
      immunocytochemistry for human lactoferrin and western blot analysis for
      lactoferrin-induced ferritin were performed in cultured T-HCECs to demonstrate
      the internalization of lactoferrin after application. RESULTS: After 2 hours,
      reoxygenation of T-HCECs after hypoxia produced an increase in cell death that
      was significantly greater than that observed in normoxic control cells or in
      cells subjected to hypoxia for the same time span without reoxygenation. The
      addition of desferrioxamine and lactoferrin at the time of reoxygenation
      significantly attenuated cellular damage. Confocal immunocytochemistry revealed
      that lactoferrin is taken into the cytoplasm of T-HCECs as early as 30 minutes
      after application. This was also demonstrated in western blot analysis by the
      upregulation of intracellular ferritin at 18 hours by the addition of iron-bound
      lactoferrin but not by iron-free lactoferrin. CONCLUSION: Reoxygenation is
      responsible for increased cellular damage after extensive hypoxia, which is
      attenuated by chelators of free iron in the cytosol, including the major tear
      protein lactoferrin.

PMID- 9660483
TI  - Cortical binocularity and monocular optokinetic asymmetry in early-onset
      esotropia.
AB  - PURPOSE: To investigate the correlation between directional asymmetry in ocular
      responses to monocularly viewed optokinetic stimuli (monocular optokinetic
      nystagmus, MOKN) and sensory fusion in infants and toddlers with early-onset
      esotropia. METHODS: Subjects were 14 infants and toddlers with early-onset
      esotropia (7-26 months old; median, 10 months), and 16 with no esotropia (6-22
      months; median, 11 months) who provided control data. Monocular optokinetic
      nystagmus in response to a 30 degrees/sec square-wave grating (0.25
      cycles/degree) was measured by electro-oculogram. Sensory fusion was assessed
      with visual evoked potentials (VEPs) to random-dot correlograms after correction
      of the strabismus angle with Fresnel prisms. RESULTS: All subjects with early
      onset esotropia had MOKN with a faster slow-phase component for temporal-to
      nasalward (TN) than nasal-to-temporalward (NT) motion. Ninety-three percent of
      subjects had MOKN asymmetry higher than the 95th percentile of the control group.
      Of subjects who cooperated with VEP fusion testing, 5 subjects with early-onset
      esotropia (45%) and 11 control subjects (92%) showed evidence of sensory fusion.
      CONCLUSIONS: Symmetrical MOKN did not develop in infants and toddlers with early
      onset esotropia. This deficit existed in most infants who showed sensory-
      cortical fusion. These results are consistent with the belief that optokinetic
      nystagmus asymmetry may not be associated with a deficit in the cortical fusion
      facility, but rather with deficits in binocular pathways projecting to MOKN
      control centers. These deficits may be associated with abnormal processing
      subsequent to sensory fusion or with abnormal processing in motion pathways,
      which run parallel to sensory fusion pathways.

PMID- 9660484
TI  - Mechanical stretch alters the actin cytoskeletal network and signal transduction
      in human trabecular meshwork cells.
AB  - PURPOSE: Human trabecular meshwork (HTM) cells were mechanically stretched in
      vitro as a potential model for the distension of this tissue that can occur in
      vivo in response to increased pressure gradients. Cell morphology and certain
      components of the signal transduction pathways, including the mitogen-activated
      protein kinase (MAPK) and c-Jun N-terminal protein kinase (JNK) pathways, were
      evaluated for stretch-induced alterations. METHODS: Primary HTM cells grown in
      tissue culture were subjected to a mechanical stretch lasting from 10 seconds to
      4 days. The actin cytoskeletal network was visualized by phalloidin staining.
      Proteins phosphorylated on their tyrosine residues were isolated using an
      immunoaffinity system and were analyzed by gel electrophoresis and
      immunostaining. Mitogen-activated protein kinase activity was evaluated using an
      in-gel assay system, and the mRNA levels of c-fos and c-jun were determined by
      quantitation of competitive reverse transcription-polymerase chain reaction. In
      addition, the amount of c-Fos protein was estimated by chemiluminescent
      immunoblot analysis. RESULTS: On stretching, the HTM cells elongated but regained
      their normal morphologic characteristics within 24 hours. Unstretched HTM cells
      displayed a diffuse F-actin microfilament network, whereas stretched cells
      exhibited complex geodesic patterns. Ten seconds after stretching began, the
      level of tyrosine phosphorylation on the six major phosphoproteins significantly
      decreased between 80% and 100%, whereas the level of paxillin tyrosine
      phosphorylation significantly increased 39%. Stretching caused MAPK activity and
      the amount of mRNA and protein of the immediate-early gene c-fos to decrease more
      than 60% within 2 minutes, but within 15 to 30 minutes they increased above or
      equivalent to normal levels. The level of c-jun mRNA was unchanged by stretching.
      CONCLUSIONS: In response to a mechanical stretch, major cytoskeletal alterations
      occur in HTM cells, which involve changes in the levels of tyrosine
      phosphorylation. Mechanotransduction (signal transduction by mechanical
      stimulation) through the MAPK signaling pathway was significantly depressed
      immediately after stretching; however, the JNK pathway appeared to be unaffected.
      The data suggest that HTM cells adapt to mechanical stress by altering the
      cytoskeletal network and signaling cascades.

PMID- 9660485
TI  - Suppression of nitric oxide generated by inflammatory macrophages by calcitonin
      gene-related peptide in aqueous humor.
AB  - PURPOSE: Ocular immune privilege is mediated in part by the activity of
      constitutively produced immunosuppressive cytokines and neuropeptides. Aqueous
      humor was examined for content of calcitonin gene-related peptide (CGRP), and the
      potential of CGRP to mediate immunosuppressive activity within aqueous humor was
      determined. METHODS: The concentration of CGRP in fresh, normal rabbit aqueous
      humor was assayed by competitive enzyme-linked immunosorbent assay. The ability
      of CGRP to suppress interferon (IFN)-gamma production by antigen-stimulated,
      primed lymph node cells was examined by assaying supernatants of stimulated CGRP
      treated, primed T-cell cultures for IFN-gamma. The anti-inflammatory activity of
      aqueous humor and CGRP was assayed by treating IFN-gamma-lipopolysaccharide (LPS)
      activated RAW 264.7 cells (macrophages) with aqueous humor, aqueous humor plus
      anti-CGRP antibody, or CGRP alone. Culture supernatants of the treated
      macrophages were examined for nitrite by Griess reagent. The production of
      inducible nitric oxide synthase (NOS2) protein was examined by immunoblotting
      cell lysates of treated activated macrophages. RESULTS: The constitutive level of
      CGRP in fresh, normal rabbit aqueous humor was 5+/-1 x 10(-5) M. At its ocular
      concentration, CGRP did not inhibit IFN-gamma production by stimulated effector T
      cells, but it suppressed nitric oxide generation by activated macrophages.
      Neutralization of CGRP in normal rabbit aqueous humor prevented the aqueous humor
      from suppressing nitric oxide generation by macrophages. Neither CGRP nor aqueous
      humor suppressed NOS2 protein synthesis in activated inflammatory macrophages.
      CONCLUSIONS: Calcitonin gene-related peptide is a constitutive neuropeptide in
      aqueous humor. Through CGRP, aqueous humor suppresses nitric oxide production by
      activated macrophages. This suppression appears to result from inhibiting NOS2
      enzymatic activity, rather than from suppressing NOS2 synthesis. The results
      imply that the ocular microenvironment has diverse immunoregulatory mechanisms
      that suppress induction, activation, and mediation of immunogenic inflammation.

PMID- 9660486
TI  - Glutathione transport in immortalized HLE cells and expression of transport in
      HLE cell poly(A)+ RNA-injected Xenopus laevis oocytes.
AB  - PURPOSE: To determine reduced glutathione (GSH) transport in cultured human lens
      epithelial cells (HLE-B3) and plasma membrane vesicles and to study the
      expression of GSH transport in Xenopus laevis oocytes injected with poly(A)+ RNA
      from HLE-B3 cells. METHODS: Confluent HLE-B3 cells pretreated with 10 mM DL
      buthionine sulfoximine and 0.5 mM acivicin were used in GSH uptake studies. The
      uptake of 35S-GSH was performed for 30 minutes in either NaCl medium (Na+
      containing) or choline chloride medium (Na+-free) at 37 degrees C and 4 degrees
      C. The molecular form of 35S uptake was determined by high-performance liquid
      chromatography. GSH uptake kinetics were studied in acivicin and buthionine
      sulfoximine-treated HLE-B3 cells in NaCl medium in the concentration range 0.01
      microM to 50 mM. The transport of GSH and the effect of Na+ on uptake also were
      determined in mixed plasma membrane vesicles from HLE-B3 cells. In oocyte
      expression studies, HLE-B3 poly(A)+ RNA was injected into X. laevis oocytes and
      GSH uptake experiments were performed 3 days after injection. The uptake of 35S
      GSH and GSH efflux rates were determined in HLE-B3 poly(A)+ RNA-injected oocytes.
      RESULTS: No significant difference was found in the uptake of 1 mM GSH+/-acivicin
      (17.7+/-4.3 versus 15.7+/-1.4 picomoles/min(-1) per 10(6) cells). However, GSH
      uptake was significantly lower in Na+-free medium compared with Na+-containing
      medium (10.3+/-0.7 versus 16.8+/-0.9 picomoles/min(-1) per 10(6) cells; P <
      0.01). GSH uptake in NaCl medium was carrier mediated. GSH uptake showed partial
      sodium dependency from 5 microM to 5 mM GSH in mixed plasma membrane vesicles
      from HLE-B3 cells. Oocytes injected with HLE-B3 poly(A) RNA expressed uptake and
      efflux of GSH. Uptake showed partial Na+ dependency at various GSH
      concentrations. The efflux rates were approximately 30-fold higher than those in
      water-injected oocytes (0.48+/-0.03 versus 0.016+/-0.005 (nanomoles per hour(-1)
      per oocyte, respectively). The molecular form of uptake in cultured cells and in
      oocyte studies was predominantly as intact GSH. CONCLUSIONS: HLE-B3 cells and
      plasma membrane vesicles transported GSH by a carrier-mediated process. HLE-B3
      poly(A)+ RNA injected X laevis oocytes expressed GSH transport. GSH uptake was
      partially Na+ dependent in all systems. HLE-B3 cells offer a useful model for
      characterizing GSH transport and for studying its regulatory role in the etiology
      of cataracts.

PMID- 9660487
TI  - Expression of growth control and differentiation genes in human lens epithelial
      cells with extended life span.
AB  - PURPOSE: Peptide growth factors including hepatocyte growth factor (HGF),
      platelet-derived growth factor (PDGF), and epidermal growth factor (EGF) are
      mitogens for many cell types and may act as regulators of lens epithelial cell
      growth and differentiation. The present study was undertaken to investigate the
      expression of growth factor receptors and crystallin genes in the human lens
      epithelial cell line HLE B-3, created by infection with Adeno12-simian virus 40
      (Ad12-SV40) hybrid virus. METHODS: Reverse transcriptase-polymerase chain
      reaction (RT-PCR) with gene-specific primers was used to detect transcripts, and
      Southern and western blot analyses were used for identification of gene products.
      Functional analysis of PDGF receptor was performed by measuring the effect of
      PDGF-BB on Ca2+ release, cell growth, and western blot analysis, by using an
      antiphosphotyrosine antibody. RESULTS: Human lens epithelial B-3 cells expressed
      the growth factor receptors HGF-R, EGF-R, and PDGF-Rbeta, but not PDGF-Ralpha,
      and also expressed the oncogenes H-ras and raf and the growth inhibitor
      transforming growth factor-beta1. Stimulation of PDGF-Rbeta with PDGF-BB in HLE B
      3 cells increased phosphorylation of the receptor, was associated with an
      increase in intracellular Ca2+ levels, and produced a small increase in cell
      growth. In addition, HLE B-3 cells expressed transcripts for alphaA-, alphaB-,
      and betaB2-crystallins, and expressed the corresponding proteins. The transcripts
      for alphaA-crystallin decreased markedly at higher passages. CONCLUSIONS: The
      above findings suggest that the increased growth potential of human lens
      epithelial cells by Ad12-SV40 infection maintained certain lens-specific
      properties and response to PDGF.

PMID- 9660488
TI  - Differential cataractogenic potency of TGF-beta1, -beta2, and -beta3 and their
      expression in the postnatal rat eye.
AB  - PURPOSE: Transforming growth factor-beta has been shown to induce cataractous
      changes in rat lenses. This study assesses the relative cataractogenic potential
      of TGF-beta1, TGF-beta2, and TGF-beta3 and their expression patterns in the rat
      eye. METHODS: Lens epithelial explants and whole lenses from weanling rats were
      cultured with TGF-beta1, TGF-beta2, or TGF-beta3 at concentrations ranging from
      0.025 ng/ml to 4 ng/ml for 3 to 5 days. Cataractous changes were monitored daily
      by phase contrast microscopy and by immunofluorescent detection of cataract
      markers alpha-smooth muscle actin and type I collagen. Expression of TGF-beta was
      studied by immunofluorescence and in situ hybridization on eye sections from
      neonatal and weanling rats. RESULTS: All three isoforms induced morphologic
      changes in lens epithelial explants and cultured lenses that are typically
      associated with human subcapsular cataract. Transforming growth factor-beta2 and
      TGF-beta3 were approximately 10 times more potent than TGF-beta1. All three
      isoforms were expressed in the eye in spatially distinct but overlapping
      patterns. Transforming growth factor-beta1 and TGF-beta2 and their mRNA were
      detected in most ocular tissues, including the lens. Although TGF-beta3 was
      immunolocalized in lens epithelium and fibers and in other ocular tissues, its
      mRNA was detected only in the retina and choroid. CONCLUSIONS: All three isoforms
      of TGF-beta are potentially available to lens cells and have the potential to
      induce cataractous changes. The results suggest that TGF-beta activity is
      normally tightly regulated in the eye. Activation of TGF-beta in the lens
      environment, such as may occur during injury, in wound healing, or in pathologic
      conditions may contribute to cataractogenesis in vivo.

PMID- 9660489
TI  - Effect of cataract surgery on aqueous TGF-beta and lens epithelial cell
      proliferation.
AB  - PURPOSE: To study lens epithelial cell (LEC) regulation after experimental
      cataract surgery in rabbits. The effect of aqueous humor (AqH) on LECs in vitro
      was investigated and the AqH concentrations of basic fibroblast growth factor
      (bFGF) and transforming growth factor-beta (TGF-beta) were determined. METHODS:
      Aqueous humor was aspirated immediately before, and 1, 5, 10, 15, and 30 days
      after cataract surgery (n=8 each day). The effect of AqH on LEC proliferation was
      investigated by the incorporation of [3H]thymidine. The following concentrations
      were determined in AqH: bFGF, active and total TGF-beta, leukocytes, and total
      protein. RESULTS: Aqueous humor collected after surgery triggered LEC growth on
      each occasion, except on (postoperative) day 30, in contrast to the effect of
      normal AqH. Lens epithelial cell proliferation peaked on day 1, displaying a
      sixfold increase. The bFGF concentration in AqH increased 6 to 10-fold after
      surgery and remained high throughout the experimental period. The AqH
      concentration of active TGF-beta decreased sevenfold 1 day after surgery. It then
      returned to normal levels on day 15. Total TGF-beta in postoperative AqH was
      twice as high as that in normal AqH on all days. Lens epithelial cell
      proliferation correlated with protein (r=0.685), leukocytes (r=0.565), and active
      TGF-beta (r=-0.418). CONCLUSIONS: The stimulating effect of postoperative AqH on
      LEC proliferation may be caused by a reduction in the concentration of TGF-beta.

PMID- 9660490
TI  - The correlation between cerebrospinal fluid pressure and retrolaminar tissue
      pressure.
AB  - PURPOSE: To measure the effects of cerebrospinal fluid pressure (CSFp) on
      retrolaminar tissue pressure (RLTp) and the translaminar pressure gradient
      (TLPG), particularly at low CSFp, which is the normal situation in erect posture.
      METHODS: Micropipettes coupled to a servonull pressure system were passed into
      eyes of anesthetized dogs to the optic disc and advanced in steps through the
      lamina cribrosa to the optic nerve subarachnoid space (ONSAS), while pressure
      measurements were taken. Cerebrospinal fluid pressure and intraocular pressure
      (IOP) were monitored and controlled. The TLPG was measured at varying IOPs and
      CSFps. The RLTp and ONSAS pressure (ONSASp) were measured at varying CSFps. In
      separate experiments, the optic nerve dura was incised, and pressure measurements
      were taken across the pia mater. RESULTS: The TLPG was strongly correlated to the
      difference between IOP and CSFp (r=0.93; n=18) when CSFp was more than zero. Mean
      RLTp was 3.7+/-0.2 mm Hg (SEM; n=15) when CSFp was 0 mm Hg. The ONSASp and RLTp
      were largely dependent on the presence of CSFp higher than break point pressures
      of -0.5 mm Hg and 1.33 mm Hg, respectively. However, below these break points,
      RLTp (slope 0.07) and ONSASp (slope 0.18) were little influenced by CSFp.
      Separate measurements across the pia mater revealed that 95% of the pressure drop
      occurred within 100 microm of the pial surface. CONCLUSIONS: The TLPG and RLTp
      are dependent on CSFp when CSFp is more than -0.5 mm Hg. Below this level, there
      is no hydrostatic continuity between the intracranial and optic nerve
      subarachnoid space. In this range, RLTp is stable and is little influenced by
      CSFp changes.

PMID- 9660491
TI  - Synergistic receptor-activated calcium increases in single nonpigmented
      epithelial cells.
AB  - PURPOSE: To determine whether single nonpigmented ciliary body cells contain the
      signaling mechanism to produce synergistic drug-activated increases in Ca2+, or
      whether these responses are produced cooperatively by interaction among groups of
      cells. METHODS: Suspensions of single nonpigmented cells were plated onto soft
      collagen gels. Fura-2 fluorescence ratio imaging was used to examine receptor
      evoked changes in intracellular Ca2+ concentration. RESULTS: Nonpigmented cells
      plated on soft collagen gels retained a rounded shape with membrane evaginations
      visible on their surface. Application of acetylcholine (10 microM) or epinephrine
      (1 microM) each produced small increases in intracellular Ca2+, but in
      combination they produced a Ca2+ increase of more than 10-fold. This synergistic
      Ca2+increase was a result of activation of muscarinic and alpha2-adrenergic
      receptors because a specific alpha2-adrenergic agonist could substitute for
      epinephrine in producing the response. The response could be blocked by a
      specific alpha2-antagonist and a muscarinic antagonist. An alpha1-agonist could
      not substitute for epinephrine in producing a synergistic increase nor could the
      synergism be blocked by alpha1- or beta-antagonists. The Ca2+ increase was
      largely produced by release from internal stores, because the peak amplitude of
      the response was nearly the same in the external solution containing a low Ca2+
      concentration; however, the influx of Ca2+ into the cell was responsible for
      maintenance of a steady component of the Ca2+ increase during maintained drug
      stimulation and for refilling the internal stores. CONCLUSIONS: Single
      nonpigmented cells can produce synergistic increases in Ca2+ on multiple receptor
      activation, indicating that the mechanism of synergism does not require the
      interaction of multiple cells. The Ca2+ increase is a result of release from
      internal stores and Ca2+ entry through an as yet undefined conductance or
      transport system in the plasma membrane.

PMID- 9660492
TI  - Carrier-mediated transport of monocarboxylate drugs in the pigmented rabbit
      conjunctiva.
AB  - PURPOSE: To determine whether an Na+-dependent monocarboxylate transport process
      exists on the mucosal side of the pigmented rabbit conjunctiva and to evaluate
      how it may contribute to the absorption of ophthalmic monocarboxylate drugs.
      METHODS: L-lactate was used as a model substrate. The excised pigmented rabbit
      conjunctiva was mounted in a modified Ussing chamber for the measurement of short
      circuit current (Isc) and 14C-L.-lactate transport. RESULTS: When added to the
      mucosal side at 37 degrees C and at pH 7.4, applications of as much as 40 mM L-
      and D-lactate increased Isc in a saturable manner. By contrast, no change in Isc
      was observed at 4 degrees C or under the mucosal Na+-free condition. 14C-L
      lactate transport in the mucosal-to-serosal (m-s) direction at 0.01 mM revealed
      directionality, temperature dependency, Na+ dependency, and ouabain sensitivity,
      but not pH dependency. L-lactate transport in the m-s direction consisted of a
      saturable Na+-dependent process by the transcellular pathway and a nonsaturable
      process by the paracellular pathway. For the saturable process, the apparent
      Michaelis-Menten constant was 1.9 mM, the maximum flux was 8.9 nanomoles/cm2 per
      hour, and the apparent Na+ :L-lactate coupling ratio was 2:1. 14C-L-lactate
      transport in the m-s direction was significantly inhibited (46% to 83%) by the
      mucosal presence of various monocarboxylate compounds, but not by dicarboxylate
      compounds, zwitterionic compound, D-glucose, amino acids, and peptidomimetic
      antibiotics. Monocarboxylate nonsteroidal anti-inflammatory drugs and the
      antibacterial fluoroquinolones inhibited 14C-L-lactate transport by 40% to 85%,
      whereas prostaglandins and cromolyn had no effect. CONCLUSIONS: An Na+-dependent
      monocarboxylate transport process that may be used by non-steroidal anti
      inflammatory and fluoroquinolone antibacterial drugs for transport appears to be
      present on the mucosal side of the pigmented rabbit conjunctiva. A possible
      physiologic role for the Na+-dependent monocarboxylate transport process may be
      to salvage tear lactate.

PMID- 9660493
TI  - Dopamine D1 stimulation of Na+,K+,Cl- cotransport in human NPE cells: effects of
      multiple hormones.
AB  - PURPOSE: To determine the effects of dopamine on Na+,K+,Cl- cotransport in human
      ciliary nonpigmented epithelial (NPE) cells. METHODS: The authors used 86Rb+ as a
      marker for K+ to study ouabain-insensitive, bumetanide-sensitive 86Rb+ uptake in
      cultured fetal human NPE monolayers. RESULTS: Na+,K+,Cl- cotransport was
      stimulated 1.63-fold by 10 microM dopamine. Stimulation was dose dependent, with
      a maximum stimulation occurring at 10 microM dopamine and an EC50 of 0.5 microM.
      NaK-ATPase (measured as ouabain-sensitive, bumetanide-insensitive 86Rb+ uptake)
      and bumetanide-insensitive, ouabain-insensitive 86Rb+ uptake were not affected by
      dopamine. The D1-receptor-specific antagonist, SCH23390, inhibited stimulation by
      10 microM dopamine more than 90% at 1 microM, with an IC50 of 4 nM, whereas the
      D2-receptor-specific antagonist, sulpiride, was over 250 times less effective.
      Similarly, a D1 agonist, SKF81297, was more potent than the D2 agonist
      bromocriptine in stimulation of Na+,K+,Cl- cotransport. The beta-adrenergic
      antagonists timolol and propranolol did not significantly inhibit stimulation of
      Na+,K+,Cl- cotransport by dopamine. Conversely, SCH23390, showed minimal
      inhibition of isoproterenol stimulation of Na+,K+,Cl- cotransport. Stimulation by
      maximally stimulating concentrations of isoproterenol and dopamine were not
      additive, but were similar to stimulation by 1 microM forskolin, suggesting that
      adenylyl cyclase may be close to maximally activated by either catecholamine. In
      vivo concentrations (stimulation approximately 25% over control) of dopamine,
      isoproterenol, and norepinephrine added together stimulated Na+,K+,Cl-
      cotransport 80% to 89% of stimulation by maximal concentrations of these drugs.
      The protein kinase A inhibitor N-[2-p-bromocinnamylaminoethyl]-5
      isoquinolinesulfonamide (H-89) blocked dopamine stimulation of Na+,K+,Cl-
      cotransport by more than 75%, whereas phorbol 12-myristate 13-acetate (PMA), a
      protein kinase C activator, given with 10 microM dopamine inhibited Na+,K+,Cl-
      cotransport by 75% to 80%, similarly to inhibition by PMA given alone.
      CONCLUSIONS: Dopamine stimulates Na+,K+,Cl- cotransport in NPE through dopamine
      D1-type receptors and activation of protein kinase A. Beta-adrenergic receptors
      do not appear to play a role. Inhibition of Na+,K+,Cl- cotransport by protein
      kinase C is dominant over stimulation of Na+,K+,Cl- cotransport through the
      cyclic adenosine monophosphate pathway.

PMID- 9660494
TI  - Antigenic changes of rabbit retinal Muller cells in culture.
AB  - PURPOSE: To determine whether dissociated and cultured Muller cells from the
      avascular rabbit retina undergo the same phenotypic changes as Muller cells that
      are dissociated and cultured from a vascular retina. METHODS: Muller cells were
      dissociated from adult rabbit retinas by using an enzymatic digestion-mechanical
      trituration technique and a cell attachment method that provided Muller cell-
      enriched cell cultures. Indirect immunofluorescence localization of vimentin,
      glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), beta-amyloid
      precursor protein (beta-APP), and (alpha-smooth muscle actin (alpha-SMA) was
      carried out on Muller cells that were freshly dissociated, on those that had been
      in culture 2 and 6 days, and on confluent primary cultures and late-passage
      cultures. The specificity of the antibodies and changes in protein expression
      were examined by western blot analysis. RESULTS: The expression of vimentin,
      GFAP, GS, and beta-APP was present 2 days after dissociation and was retained
      through 6 days in culture, at which time alpha-SMA began to be expressed in a
      small number of cells. The confluent, primary cultures no longer expressed GS,
      but vimentin and beta-APP were still expressed, and the expression of alpha-SMA
      was increased. During the late-passage stage, the morphologic appearance of the
      Muller cell cultures was large and amorphous, with additional changes in
      antigenicity. Although there was loss of expression of the intermediate filament
      proteins GFAP and vimentin, the expression of beta-APP was maintained, whereas
      alpha-SMA was increased and appeared to be a major cytoskeletal protein.
      CONCLUSIONS: Dissociated Muller cells that were maintained in culture underwent
      phenotypic changes that included a large, amorphous appearance; the loss of
      detectable vimentin, GFAP, and GS expression; the persistent presence of beta
      APP; and the de novo appearance of alpha-SMA. The phenotypic and antigenic
      changes that occurred in cultured Muller cells from an avascular retina were
      similar but not identical to the changes observed in cultured Muller cells from a
      vascular retina.

PMID- 9660495
TI  - Submicrovolt flicker electroretinogram: cycle-by-cycle recording of multiple
      harmonics with statistical estimation of measurement uncertainty.
AB  - PURPOSE: To study cycle-by-cycle recording of small-amplitude flicker
      electroretinogram (ERG) responses and analyze results with robust statistical
      methods to estimate the measurement uncertainty. METHODS: Flicker ERGs at 32 Hz
      were recorded simultaneously from both eyes of patients with retinal
      degeneration. The ERG was amplified under wide-band (1-1000 Hz) conditions,
      digitized at 6144 Hz/eye, and multiplied point for point (192 points/cycle) by
      sine and cosine functions within each 1/32-second flash cycle to extract
      coefficients for six harmonic components of a discrete Fourier transform in real
      time. Amplitude windowing was not used, and all data were saved for subsequent
      statistical processing to identify and remove large-amplitude artifacts
      discretely and to search for quiet recording periods that minimized small
      amplitude noise. RESULTS: Plots of amplitude and phase indicated far outlying
      noise points that were excised from the data. The SD of sequential intervals on a
      time line of the sine component identified quiet periods that minimized small
      amplitude noise and improved measurement consistency. The SE of the response mean
      provided an estimate of measurement uncertainty. CONCLUSIONS: The harmonic
      components of many individual responses are captured quickly (e.g., 500 responses
      in 15.6 seconds) for post hoc statistical analysis, using mathematical algorithms
      that are precisely reproducible to facilitate comparison of results from all
      laboratories. Graphical time lines of responses allow separation of artifact
      transients from gaussian noise for elimination of noisy periods without
      disturbing the stored information. Statistical estimates of measurement
      uncertainty are determined on-line to allow immediate feedback during the
      recording session. Amplitude-phase plots of the multiple harmonic components,
      along with reconstructed analog waveforms, provide results in a readily
      assimilated manner for comparison of all testing sessions.

PMID- 9660496
TI  - Protective effect of adult T-cell leukemia-derived factor on retinal ischemia
      reperfusion injury in the rat.
AB  - PURPOSE: To evaluate the protective effects of recombinant adult T-cell leukemia-
      derived factor (ADF)-human thioredoxin against ischemia-reperfusion injury in the
      rat retina. METHODS: Retinal ischemia was induced in rats by increasing the
      intraocular pressure to 110 mm Hg for 60 minutes. Various doses of recombinant
      human ADF (rhADF) or vehicle were administered intravenously before ischemia
      induction and immediately after reperfusion. The degree of retinal damage was
      assessed by electroretinogram (ERG) recording, by measuring the inner retinal
      thickness, and by counting the number of TdT-dUTP terminal nick-end labeling
      (TUNEL)-positive cells in the inner nuclear layer. RESULTS: The amplitudes of the
      ERG b-wave and oscillatory potentials were increased significantly by treatment
      before ischemia and after reperfusion with 0.5 mg or 5 mg rhADF and by treatment
      after reperfusion with 1 mg rhADF, compared with those of vehicle-treated control
      rats (P < 0.01). On day 28 after reperfusion, the thickness of the inner retina
      of control rats and of rats treated before ischemia and after reperfusion with
      0.5 mg rhADF were 46.1+/-6.4 microm and 78.5+/-8.9 microm, respectively (P <
      0.01). The number of TUNEL-positive cells on days 1 and 2 after reperfusion was
      decreased significantly by treatments with 0.5 mg rhADF compared with the number
      of TUNEL-positive cells in control rats (P < 0.01). CONCLUSIONS:
      Electrophysiologic and histologic studies showed that ischemia for 60 minutes
      produces severe damage in vehicle-treated control rat retina, particularly in the
      inner retinal layer. Intravenous injection of rhADF protects the rat retina from
      ischemia-reperfusion injury.

PMID- 9660497
TI  - Autofluorescent inclusions in long-term postconfluent cultures of retinal pigment
      epithelium.
AB  - PURPOSE: To examine the accumulation and morphologic features of fluorescent
      inclusions in retinal pigment epithelial (RPE) cells in vitro and to determine
      whether accumulation correlates with parameters of age. METHODS: Cultured human
      RPE cells were maintained undisturbed at confluence for intervals as long as 2
      years and then were examined for autofluorescent inclusions by fluorescence and
      electron microscopy, with comparisons to the lipofuscin of freshly isolated RPE.
      Autofluorescence was also examined in bovine RPE cultures that were aged in vitro
      by replicative senescence. In some postconfluent cultures,the activity of the
      lysosomal enzyme cathepsin D was measured, and the effect of cell growth on
      autofluorescence was examined by reinducing cell proliferation in late-stage
      cultures. RESULTS: Autofluorescent inclusions accumulated in human and bovine RPE
      cultures after extended postconfluent periods. Accumulation was not accelerated
      in cultures from older donors or in cultures that were aged in vitro. The number
      of granules per RPE cell varied for lipofuscin in situ and inclusions in vitro,
      although the latter were more heterogeneous in size and shape and in
      ultrastructural appearance of the granule contents. Lipofuscin and
      autofluorescent inclusions were lost when RPE cells were propagated, but in
      contrast to lipofuscin, the inclusions became smaller and fainter when growth was
      reinduced in postconfluent cultures. Cathepsin D activity varied among cultures
      and showed no significant change as time elapsed after confluence. Activity
      increased after repropagation of long-term postconfluent cultures. CONCLUSIONS:
      In the absence of phagocytic challenge with photoreceptor outer segments,
      postconfluent RPE cultures accumulate heterogeneous materials that show
      autofluorescence. Accumulation is associated with one marker of age: time at
      confluence, which simulates a long-term, nonmitotic state similar to that which
      occurs in situ during aging in postproliferative tissues. The autofluorescent
      inclusions in vitro predictably differ from autofluorescent lipofuscin in situ,
      presumably because the inclusions formed in culture are derived from RPE
      autophagy alone. Postconfluent cultures can be used to examine the molecular and
      biologic properties of materials originating only from an autophagic source, or
      coupled with phagocytic challenge to produce a model of developing RPE lipofuscin
      that has an autophagocytic and a heterophagic component, similar to RPE cells in
      situ.

PMID- 9660498
TI  - Fluorescence properties of autofluorescent granules generated by cultured human
      RPE cells.
AB  - PURPOSE: To compare the fluorescence properties of autofluorescent granules
      generated by retinal pigment epithelial (RPE) cells in vitro with those of the
      lipofuscin of RPE in vivo. METHODS: Cultured human RPE cells were maintained in
      basal medium for as long as 1 year, fed rod outer segments (ROS) daily for as
      long as 56 days, fed ROS in the presence and absence of leupeptin, or fed
      liposomes consisting of the major phospholipids in ROS. At different time points,
      cells were examined for overall fluorescence, and their fluorescence spectra were
      determined. In addition, chloroform-methanol extracts were examined by thin-layer
      chromatography and compared with those generated from RPE lipofuscin. RESULTS:
      Autofluorescent granules accumulated in cultured RPE cells, regardless of the
      presence of an exogenous substrate or the nature of the substrate. The rate of
      accumulation of autofluorescent granules was greatest in cells fed ROS. The
      autofluorescent material generated in cultured RPE cells had some spectral
      similarities with RPE lipofuscin but differed in solubility and chromatographic
      mobility of their constituent fluorophores. CONCLUSIONS. The autofluorescent
      granules generated by cultured RPE, even with different specific substrates,
      differ from lipofuscin granules in vivo, suggesting that additional properties of
      RPE cells or of the materials they phagocytose are required to produce
      autofluorescent materials with the characteristics of lipofuscin.

PMID- 9660499
TI  - A decreased Ca2+-wave propagation is found among cultured RPE cells from
      dystrophic RCS rats.
AB  - PURPOSE: The authors investigated intercellular communication among cultured rat
      retinal pigment epithelial (RPE) cells isolated from dystrophic Royal College of
      Surgeons (RCS) rats by studying the conduction of the [Ca2+]i wave elicited by
      mechanical stimulation. The effect of protein phosphorylation was measured by
      modulating the protein kinase C (PKC), protein kinase A (PKA), and tyrosine
      kinase activity. METHODS: Cultured RPE cells isolated from neonatal control Long
      Evans (LE) and dystrophic RCS rats were analyzed using the fluorescent dye fluo-3
      to measure the Ca2+-wave propagation on mechanical stimulation to investigate the
      intercellular communication. RESULTS: Mechanical stimulation in LE-RPE cells
      resulted in a centrifugally spreading Ca2+ wave through the neighboring cells.
      When a mechanical stimulus was applied on RCS-RPE cells, a significantly reduced
      Ca2+-response was found in the neighboring cells compared with that of control
      RPE cells. Activation of PKC almost completed blocked the mechanically induced
      Ca2+ rise in the neighboring RCS-RPE cells. In contrast to LE-RPE cells, an
      activation of PKA also significantly decreased the Ca2+-wave propagation in RCS
      RPE cells. Inhibition of PKA had no effect on the intercellular communication in
      LE- or RCS-RPE cells. In addition, when protein phosphatase activity or tyrosine
      kinase activity was inhibited, an increased Ca2+ rise in the neighboring cells on
      mechanical stimulation was measured, reaching levels currently found for LE-RPE
      cells. CONCLUSIONS: In dystrophic RCS-RPE cells, a decreased intercellular Ca2+
      wave propagation is found. This intercellular communication can be mediated by
      protein phosphorylation.

PMID- 9660500
TI  - Gene transfer to the human trabecular meshwork by anterior segment perfusion.
AB  - PURPOSE: To determine whether adenovirus vectors are capable of transferring a
      foreign active protein to the perfused anterior segment of the human eye.
      METHODS: Primary cultures from the human trabecular meshwork tissue were exposed
      to replication-deficient adenovirus Av1LacZ4 carrying the reporter beta
      galactosidase gene driven by the Rous Sarcoma Virus promoter. Anterior segments
      of six pairs of human eyes from normal donors were placed in organ culture and
      were perfused with culture medium at 2.5 microl/min constant flow. After 24
      hours, one eye was injected once with 8 X 10(8) plaque-forming units (20 microl)
      of the viral vector, while the paired eye was injected with vehicle. Forty-eight
      hours (four pairs) and 7 days (two pairs) after injection, tissues were fixed,
      were assayed histochemically for transferred enzyme activity, and were analyzed
      morphologically. RESULTS: In monolayers, gene transfer occurs very efficiently in
      all distinct types of human outflow pathway cells. All human anterior segments
      injected with the adenovirus vector showed active gene transfer in cells of the
      outflow pathway: trabecular, juxtacanalicular, and inner wall of Schlemm's canal.
      Expression of the reporter enzyme was still present at 7 days after treatment. No
      activity was observed in any of the paired, vehicle-injected controls. Cell
      morphology and tissue architecture appeared normal in treated and control
      tissues, although some trabecular cell loss was observed in the corneoscleral and
      uveal regions of the perfused treated eyes. CONCLUSIONS: Adenoviral vectors were
      able to transfer active foreign genes into perfused, intact human trabecular
      meshwork.

PMID- 9660501
TI  - Correlates of lens thickness: the Beaver Dam Eye Study.
AB  - PURPOSE: To evaluate the relationships of lens thickness to age, to the presence
      of a nuclear, cortical, or posterior subcapsular cataract, and to other personal
      characteristics in participants in the Beaver Dam Eye Study. METHODS: Slit lamp
      photographs taken during a population-based prevalence study were measured for
      lens thickness. In addition, slit lamp photographs were graded for nuclear
      cataracts, and retroillumination photographs were graded for cortical and
      posterior subcapsular cataracts. A questionnaire was administered, and height,
      weight, and blood pressure were measured by protocol. RESULTS: Lens thickness
      increased systematically with age in men and women. In multivariate analysis,
      age, sex (male), cortical cataract, diabetes, nuclear cataract, and former
      cigarette smoking were related significantly to lens thickness. CONCLUSIONS: Age
      was the most significant personal characteristic associated with lens thickness
      among those subjects considered. In addition, other characteristics, including
      specific cataract types and risk factors for cataracts, also were associated with
      thickness. Whether lens thickness among people of the same age is associated
      prospectively with these characteristics requires a longitudinal follow-up.

PMID- 9660502
TI  - Cryopreservation and culture of human corneal keratocytes.
AB  - PURPOSE: To assess the effects of two different concentrations of albumin in a
      cryoprotective solution and two freezing methods on human corneal keratocyte
      ctyopreservation. METHODS: Isolated keratocytes were used for cryopreservation.
      Solutions of 10% dimethylsulfoxide with either 2% or 10% human albumin were used
      as cryoprotective agents. Cells either were transferred directly into a -80
      degrees C freezer (freezing rate, 2 degrees C/min) or were cooled in a programmed
      freezer (1 degrees C/min until -40 degrees C and then 10 degrees C/min), which
      resulted in four different cryopreservation protocols. Cells were stored at -80
      degrees C, then were thawed at 37 degrees C, and subsequently were cultured.
      Keratocytes were studied by means of trypan blue staining, growth assay,
      apoptosis assays, transmission electron microscopy, and immunochemistry. RESULTS:
      The percentage of cells that were alive after thawing ranged from 80% to 99% by
      trypan blue staining and from 45% to 60% by flow cytometry. The ratio of the
      number of living cells at the end of primary culture after cryopreservation to
      that before cryopreservation was significantly (P=0.04) higher after direct
      transfer into the -80 degrees C freezer than after controlled-rate freezing,
      whereas the albumin concentration had no significant influence on this ratio
      (P=0.45). The percentage of apoptotic cells was significantly higher after
      cryopreservation than in the control group of noncryopreserved cells; more than
      5% 24 hours after thawing. Cryopreservation did not modify the keratocyte
      ultrastructure. Fibroblast growth factor dramatically decreased the serum-induced
      cell expression of alpha smooth muscle actin, whereas cryopreservation had no
      influence on this cell expression. CONCLUSIONS: A freeze-thaw trauma, which was
      related to cryopreservation-induced cell apoptosis, was revealed during primary
      culture after thawing. Direct transfer into the -80 degrees C freezer resulted in
      better postcryopreservation growth in the culture than controlled-rate freezing.
      A change in albumin concentration from 2% to 10% did not affect the results.

PMID- 9660503
TI  - A comparison of the optical Stiles-Crawford effect and retinal densitometry in a
      clinical setting.
AB  - PURPOSE: To compare the measurement of the optical Stiles-Crawford effect (SCE)
      to the densitometry of cone visual pigments in a clinical setting. Both tests
      provide information on outer retinal integrity, but the optical SCE can be
      performed in far less time. METHODS: Images acquired with a custom-built scanning
      laser ophthalmoscope were used to assess visual pigment density and optical SCE.
      Visual pigment density was regarded as the "gold standard." More than 100
      patients with suspected, and some with known, outer retinal pathology were
      tested. The group included cases of central serous detachment, cone dystrophy,
      Stargardt's disease, Best's disease, and retinitis pigmentosa. RESULTS:
      Parameters of the optical SCE of 25 healthy subjects and 106 patients were taken
      through a stepwise linear regression to predict density. The correlation between
      predicted density from the optical SCE and the measured density was 0.82. The
      sensitivity of the optical SCE to detect decreased density was 96%. When only the
      foveal reflectance was considered, sensitivity was still 84% CONCLUSIONS: The
      optical SCE is a sensitive and fast method for detecting cone photoreceptor
      disturbances.

PMID- 9660504
TI  - A prospective study of matrix metalloproteinases in proliferative
      vitreoretinopathy.
AB  - PURPOSE: The migration, proliferation, differentiation, and adhesion of cells and
      other cellular functions are influenced by the surrounding extracellular matrix,
      in normal and wound-healing conditions. The matrix metalloproteinases (MMPs) are
      a family of enzymes that degrade and remodel the extracellular matrix and, thus,
      play a central role in the wound-healing process. Proliferative vitreoretinopathy
      (PVR), a wound-healing process in the retina, is a major cause of the failure of
      retinal detachment surgery. The role of MMPs in the pathobiology of PVR is
      unknown. We have investigated the presence of MMPs in the vitreous of patients
      with retinal detachment and the predictive value of MMPs for the future
      development of PVR. METHODS: A prospective study was conducted on 140 consecutive
      patients with a rhegmatogenous retinal detachment in whom vitrectomy was
      considered necessary because of a giant retinal tear and the presence of
      preoperative PVR, among other reasons. Vitreous samples were obtained and
      analyzed by zymography for the presence of MMPs. The patients were then followed
      up for the development of postoperative PVR (mild and severe). RESULTS: Two
      species of MMPs were detected in the vitreous: MMP-2 and MMP-9. MMP-2 was
      detected in all of the vitreous samples obtained, whereas MMP-9 was found in only
      64 (47%) of 136 samples. The levels of MMPs detected were not significantly
      associated with the presence of preoperative PVR (P > 0.05), but they were
      significantly associated (P < 0.05) with the development of postoperative PVR
      (mild and severe). CONCLUSIONS: The results from this prospective study suggest
      that MMPs may be an important predictor and may also play a role in the
      development of postoperative PVR.

PMID- 9660505
TI  - Idiopathic hyperCKemia revisited.

PMID- 9660506
TI  - Congenital muscular dystrophy with complete laminin-alpha2-deficiency, cortical
      dysplasia, and cerebral white-matter changes in children.
AB  - Congenital muscular dystrophy consists of Fukuyama congenital muscular dystrophy,
      Walker-Warburg syndrome, muscle-eye-brain disease, and occidental congenital
      muscular dystrophy, which is further divided into laminin-alpha2-positive and
      laminin-alpha2-negative subgroups. These forms of congenital muscular dystrophy
      are frequently associated with abnormal white-matter changes, whereas the
      Fukuyama form, Walker-Warburg syndrome, and muscle-eye-brain disease are also
      frequently found to have polymicrogyria. We now report two infants with complete
      laminin-alpha2-deficiency who have not only abnormal cerebral white-matter
      lesions, but also bioccipital polymicrogyria. There are significant similarities
      in the clinical and cerebral manifestations among the various types of congenital
      muscular dystrophy. The diagnosis of the Fukuyama form, laminin-alpha2
      deficiency, Walker-Warburg syndrome, and muscle-eye-brain disease cannot always
      be established on radiological studies alone.

PMID- 9660507
TI  - REM-sleep motor disorder in children.
AB  - In 1986, Schenck and coworkers described REM-sleep behavior disorder as a
      treatable parasomnia affecting older males. This disorder is characterized by
      intermittent loss of the muscle atonia, which normally characterizes the rapid
      eye movement (REM) sleep state. Complex motor behaviors occur that are often
      injurious and are associated with dreaming. We have identified five children who
      meet the criteria for REM-sleep behavior disorder and describe the clinical and
      polysomnographic characteristics of these patients, along with corresponding
      polysomnographic characteristics of matched comparison subjects.

PMID- 9660508
TI  - Trends in incidence and severity of intraventricular hemorrhage.
AB  - The incidence of germinal matrix-intraventricular hemorrhages declined from 50%
      in 1977 to 24% in 1985. Over the last decade intraventricular hemorrhage rates
      ranging from 8% to 56% were reported, leaving uncertainty as to the direction of
      recent intraventricular hemorrhage trends. Records of all 1950 neonates weighing
      2250 g or less at birth (867 weighing 1500 g or less and 1083 weighing 1501-2250
      g) at a university neonatal intensive care unit between 1986 and 1995 were
      studied. Intraventricular hemorrhage rate declined by 53%, from 11.5% in 1986 to
      5.5% in 1995 (P < .01), and was consistent across all birthweight groups: 750 g
      or less from 36% to 24%, 751-1000 g from 38% to 22%, 1001-1250 g from 19% to 13%,
      1251-1500 g from 12% to 2% and 1551-2250 g from 3% to 0.2% (P < .05).
      Proportionately, severe intraventricular hemorrhage (grades 3 +/-
      intraparenchymal hemorrhage) declined from 70% of all intraventricular
      hemorrhages in 1986 to 23% in 1995 (P < .005). Overall mortality declined by 65%
      between 1986 and 1995 (P < .001), whereas mortality associated with
      intraventricular hemorrhage declined by 30% (P = .34). Despite dramatic declines
      in intraventricular hemorrhage rates, 21% of infants weighing less than 1000 g
      and 12% of those weighing less than 1500 g at birth were affected in 1995.

PMID- 9660510
TI  - Learning disabilities with and without attention-deficit hyperactivity disorder:
      parents' and teachers' perspectives.
AB  - Our objective was to delineate the educational and behavioral differences between
      learning disabled children with and without attention-deficit hyperactivity
      disorder (ADHD). A restrospective (TROHOC) multimeasure comparative design was
      employed. Parents' and teachers' questionnaires (ANSER system) pertaining to
      attention-activity, associated behaviors, and scholastic achievements were
      compared. Parents' questionnaires failed to distinguish between the two groups.
      Teachers' questionnaires were significantly more sensitive. Significant
      correlations between educational achievements and attention-activity and
      associated behaviors scores among children with learning disabilities were
      evident, no such correlations were found in the group with learning disability
      with ADHD. The factor analysis identified different educational and behavioral
      aggregates with language related difficulties and externalizing behaviors more
      typically aggregated in the learning disabled group with ADHD and recall deficit
      and internalizing/neurotic behaviors in the group with learning disability only.
      ADHD appears to be an associated comorbidity and not necessarily a specific
      learning deficit. However, children with learning disability with ADHD possibly
      have a different underlying neurocognitive pattern than their peers with learning
      disabilities only.

PMID- 9660509
TI  - Neurologic perspectives of Crigler-Najjar syndrome type I.
AB  - Limited information exists on the neurologic sequelae of Crigler-Najjar syndrome
      type I despite this being the major morbidity of this rare autosomal recessive
      disorder of bilirubin conjugation that results in chronic unconjugated
      hyperbilirubinemia. Two patients with identical underlying genetic mutations
      resulting in Crigler-Najjar syndrome type I were assessed from a
      neurodevelopmental perspective in late childhood using age appropriate
      standardized measures. In addition, the English language literature of case
      reports and series describing the outcomes of patients with this disorder was
      reviewed (descriptive meta-analysis) and summarized with particular reference to
      neurologic symptomatology, pattern of neurologic disability, age of onset of
      symptoms, and therapeutic interventions. Despite radically different therapeutic
      interventions, our two patients did not differ in outcome measures. Review of the
      literature reveals distinct, often age-related, patterns of neurologic sequelae
      reflecting injury to basal ganglia, cerebellar, and likely hippocampal
      structures. Definitive prevention of the neurologic sequelae that often occur
      within the context of Crigler-Najjar syndrome type I requires that curative
      treatment (hepatic transplantation, presently, and gene therapy in the future) be
      applied prior to the possible onset of neurologic symptoms in adolescence.

PMID- 9660511
TI  - Gender study of neuropsychological and neuromotor function in children with
      Tourette syndrome with and without attention-deficit hyperactivity disorder.
AB  - Neuropsychological and neuromotor functions were compared between boys and girls
      with Tourette syndrome (TS only), attention-deficit hyperactivity disorder (ADHD
      only), Tourette syndrome with ADHD (TS+ADHD), and a comparison group, in an age
      (mean = 10 years) and IQ (Wechsler Full-Scale mean = 111) matched sample (n =
      116). There were no timed-task neuromotor differences among the groups. Analyses
      of variance revealed a group x gender interaction for Letter Word Fluency and the
      Rapid Automatized Naming test. Girls with ADHD only were faster than boys on both
      tasks. When data for girls only were analyzed, girls with Tourette syndrome with
      ADHD had the greatest variability of reaction time on the Test of Variables of
      Attention, and were slowest on Letter Word Fluency. Girls with TS only were
      slower than girls in the other three groups on Letter Word Fluency. Poor Letter
      Word Fluency is explained as a linguistic executive dysfunction involving speed
      and efficiency of memory search in this bright group of girls with Tourette
      syndrome, not otherwise at risk for linguistic difficulties.

PMID- 9660512
TI  - Asthma and epilepsy: are they related? A retrospective study.
AB  - Numerous studies have suggested that epilepsy and asthma may be related
      conditions. There has, however, been little epidemiologic data published to
      support this association. We conducted a retrospective study to determine whether
      the prevalence of epilepsy is increased among children with asthma, and the
      prevalence of asthma is increased among children with epilepsy, in comparison
      with the general pediatric population. We reviewed the medical records, at a
      large city hospital, of two groups of pediatric outpatients: (1) 400 consecutive
      patients with asthma followed regularly at the asthma and allergy clinic; and (2)
      201 consecutive patients with idiopathic epilepsy followed regularly at the
      pediatric neurology clinic. Patients with a history of birth prior to 36 weeks'
      gestational age were excluded. Among the 400 cases of asthma, there were three
      patients with idiopathic epilepsy (prevalence of 0.75%). The prevalence of
      epilepsy was similar in mild (0.79%) and moderate-to-severe (0.73%) asthma. Among
      the 201 cases of idiopathic epilepsy, there were 12 patients with asthma
      (prevalence of 5.97%). Similar percentages of epilepsy patients with and without
      asthma reported generalized tonic-clonic, complex partial, simple partial, and
      myoclonic seizures as their predominant type. The prevalence values in this study
      are consistent with the prevalence of epilepsy and asthma in the general
      pediatric population. Our findings therefore suggest that idiopathic epilepsy and
      asthma are not etiologically related or mutually predisposing conditions. Small
      samples, failure to exclude patients born prematurely, and the equation of
      electroencephalographic (EEG) abnormalities with epilepsy may account for the
      results of previous studies.

PMID- 9660513
TI  - Fever, heatstroke, and hemorrhagic shock and encephalopathy.

PMID- 9660514
TI  - Forearm semi-ischemic exercise test in pediatric patients.

PMID- 9660515
TI  - Muscle type promoter and its first intron abnormalities in dystrophin gene in
      patients with Duchenne muscular dystrophy.

PMID- 9660517
TI  - Paroxysmal downgaze in term newborn infants.

PMID- 9660516
TI  - Falsely elevated urinary ethanolamine levels due to vigabatrin.

PMID- 9660519
TI  - Acute confusion and mutism as a presentation of thalamic strokes secondary to
      deep cerebral venous thrombosis.

PMID- 9660518
TI  - Transient motor aphasia and recurrent partial seizures in a child: language
      recovery upon seizure control.

PMID- 9660520
TI  - Pharmacological profile of barnidipine: a single optical isomer dihydropyridine
      calcium antagonist.
AB  - This article reviews the pharmacological profile of the dihydropyridine calcium
      antagonist (CaA) barnidipine [(+)-(3'S,4S)-3-(1'-benzyl-3'-pyrrolidinyl)-methyl
      2,6-dimethyl-4-(m-nit rophenyl)-1,4dihydropyridine-3,5-dicarboxylate x HCl]. The
      characteristics and potential advantages of its pharmacological selectivity are
      also outlined. Barnidipine is an L-type CaA with high affinity for
      [3H]nitrendipine binding sites (Ki = 0.21 nmol/l). Its pharmacological profile
      has been studied in a variety of isolated tissues and animal models, such as
      isolated coronary arteries (pig, dog, rat), aorta (guinea pig) and in
      hypertensive rats (spontaneously hypertensive, renal hypertensive,
      desoxycorticosterone acetate [DOCA]-salt). Barnidipine may be characterized as a
      highly potent drug with vasoselectivity and, accordingly, a lack of negative
      inotropic activity. The onset of its action in vivo is slow, and it does not
      elicit reflex tachycardia. Its long duration of action, due to its lipophilicity,
      means that satisfactory control of elevated blood pressure can be obtained with
      once-daily dosing. Another interesting feature of barnidipine is its
      stereoselectivity. As the barnidipine molecule contains two chiral centres, it
      can have four possible enantiomers. The active component in the capsules used
      clinically consists of the S,S form, which is the most potent and longest acting
      of the four enantiomers.

PMID- 9660521
TI  - Distinct vasodilation, without reflex neurohormonal activation, induced by
      barnidipine in hypertensive patients.
AB  - Barnidipine is a new 1,4-dihydropyridine calcium antagonist with a strong and
      long-lasting vasodilatory effect. In order to assess the haemodynamic profile of
      the antihypertensive effect of barnidipine, a randomized, double-blind study of
      barnidipine vs nitrendipine was performed in 24 patients with mild to moderate
      essential hypertension. Following an initial 4-week placebo period, patients
      whose sitting diastolic blood pressure (SiDBP) was between 95 and 114 mm Hg, and
      whose sitting systolic blood pressure was between 150 and 219 mm Hg, were
      randomized (2:1 ratio) to receive either barnidipine (10 mg) or nitrendipine (10
      mg) once daily, for a 6-week double-blind period. Subsequently, patients with an
      SiDBP of less than 90 mm Hg continued for a second 6-week period with the same
      monotherapy, while patients with an SiDBP of 90 mm Hg or above received double
      the dose of antihypertensive treatment for the next 6 weeks. Two-dimensional M-
      and B-mode echocardiography with Doppler flowmetry was performed at the end of
      both the placebo and active treatment phases. Barnidipine and nitrendipine
      reduced blood pressure by the same degree (barnidipine: from 165 +/- 2/100 +/- 1
      to 145 +/- 2/89 +/- 1 mm Hg, p < 0.01; nitrendipine: from 163 +/- 3/100 +/- 2 to
      143 +/- 7/90 +/- 3 mm Hg, p < 0.01) as a result of peripheral vasodilation. This
      was not accompanied by reflex neurohormonal activation. Moreover, only in the
      group receiving barnidipine was a significant decrease in plasma noradrenaline
      observed, both when the patients were in the supine position (from 298 +/- 27 to
      214 +/- 21 pg/ml, p < 0.05) and when they were upright (from 472 +/- 37 to 348 +/
      38 pg/ml, p < 0.05).

PMID- 9660522
TI  - Efficacy and tolerability of once-daily barnidipine in the clinical management of
      patients with mild to moderate essential hypertension.
AB  - Four multicentre trials have investigated the efficacy and tolerability of
      treatment with once-daily, modified-release capsules of barnidipine, a long
      acting dihydropyridine calcium antagonist, in patients with mild to moderate
      essential hypertension. In two of these trials, the clinical profile of
      barnidipine was compared with those of amlodipine and nitrendipine, which belong
      to the same class of drug as barnidipine, in a randomized, double-blind, parallel
      group manner. In one study, 37 patients received amlodipine and 79 patients
      received barnidipine. In a second study, 46 patients received nitrendipine and 96
      received barnidipine. In each trial, a 4-week placebo run-in phase was followed
      by a 12-week comparative phase. Changes in sitting and standing diastolic and
      systolic blood pressures were assessed, and adverse events were recorded. Both
      studies demonstrated that the antihypertensive efficacy of barnidipine was
      equivalent to each comparator agent, but barnidipine tended to produce fewer
      class I adverse reactions. The long-term efficacy and safety of barnidipine were
      demonstrated in an open-label study. In total, 106 patients were followed for the
      first year of the study, during which time they received barnidipine at a dose
      titrated to achieve a sitting diastolic blood pressure of less than 90 mm Hg; if
      necessary, another antihypertensive agent was added to achieve normalization of
      blood pressure. Seventy-nine of these patients, most of whom were maintained on
      barnidipine monotherapy, were followed for a second year, and 32 patients, all of
      whom received barnidipine monotherapy throughout the study period, were followed
      for a third year. Blood pressure normalization after 1 year of follow-up was
      achieved in 91% of patients, and was maintained for the second and third years in
      91% and 81% of patients, respectively. The incidence of adverse events, possibly
      or probably attributable to barnidipine, was 22%, 14% and 3%, respectively,
      during each successive year. The suitability of barnidipine for once-daily dosing
      was confirmed in a randomized, double-blind, placebo-controlled, crossover study
      of 20 patients. These patients were given 6-week regimens of both barnidipine (20
      mg) and placebo, preceding 24-h ambulatory blood pressure monitoring. Barnidipine
      lowered blood pressure to a significantly greater extent than placebo both at
      night and during the day. These studies suggest that barnidipine possesses
      equivalent efficacy to amlodipine and nitrendipine, but produces fewer class
      specific side-effects. It provides 24-h efficacy from a once-daily dosing
      regimen, and this efficacy and its safety profile are maintained for at least 3
      years.

PMID- 9660523
TI  - The role of combination therapy in the treatment of hypertension.
AB  - Antihypertensive therapy is indicated for reducing the risk of cardiovascular
      morbidity and mortality that accompanies arterial hypertension. Usually,
      pharmacological treatment is started as monotherapy, which, if unsuccessful, is
      followed by sequential monotherapy, or by combination therapy. Recent data
      indicate that combination therapy is required in more than 50% of the
      hypertensive population when the goal is to reduce blood pressure to below 140/90
      mm Hg. The choice and doses of drugs used in combination therapy should be such
      that their synergistic effect on blood pressure is maximized, the tolerability of
      the drugs is maintained and side-effects are minimized. The combination of a
      dihydropyridine calcium antagonist with a beta-blocker or an angiotensin
      converting enzyme (ACE) inhibitor is one of the most commonly used combination
      therapies. Two randomized, double-blind, parallel-group studies compared the
      antihypertensive effects of the dihydropyridine, barnidipine, with the beta
      blocker, atenolol (n = 247), and the ACE inhibitor, enalapril (n = 155). The
      efficacy and tolerability of barnidipine in combination with either atenolol or
      enalapril was also investigated. Monotherapy with barnidipine was as effective in
      reducing blood pressure as monotherapy with either atenolol or enalapril.
      Combining barnidipine with either atenolol or enalapril reduced blood pressure
      further, and significantly increased the percentage of patients attaining the
      required reduction in blood pressure. When patients whose blood pressure was not
      adequately controlled by enalapril monotherapy were switched to barnidipine
      monotherapy, the majority then achieved the desired reduction in blood pressure.
      These results indicate that if barnidipine monotherapy fails to lower blood
      pressure to the desired values, its combination with either a beta-blocker or an
      ACE inhibitor is effective and well tolerated.

PMID- 9660524
TI  - Diversity and intensity of adverse events in the treatment of hypertension with
      barnidipine.
AB  - Calcium antagonists (CaAs) are divided into three structural classes, typically
      represented by verapamil, diltiazem and nifedipine. As a group, the principal
      (type I) adverse effects of these drugs relate to the pharmacological action of
      calcium channel blockade, namely vasodilation, and include dizziness, flushing,
      palpitations and peripheral oedema. The clinical safety of the new
      dihydropyridine CaA, barnidipine, has been assessed in more than 12 clinical
      trials, including 2041 patients who have been treated with one or more doses of
      barnidipine (dose of up to 50 mg). Adverse events with barnidipine are of mild to
      moderate intensity, most commonly of type I, occurring in the early phase of
      treatment. The incidence of serious adverse events and the rate of withdrawals
      are low. Hence, barnidipine is likely to be well tolerated in general clinical
      use.

PMID- 9660525
TI  - Morbidity and mortality with dihydropyridines.
AB  - Calcium antagonists (CaAs) of the dihydropyridine type are widely used in the
      treatment of hypertension and other cardiovascular disorders. They are markedly
      effective in lowering elevated arterial pressure, and are well tolerated. Data
      from long-term intervention trials are emerging, which also show a beneficial
      effect on cardiovascular morbidity with the use of CaAs in the treatment of
      hypertension. The first such evidence was from the Shanghai Trial of Nifedipine
      in the Elderly (STONE), and, in February 1997, the Systolic Hypertension in
      Europe (Syst-Eur) trial was stopped prematurely because the active treatment,
      based on a CaA, was found to be significantly better than placebo in preventing
      cardiovascular disease. In addition, ongoing trials with dihydropyridine CaAs
      (e.g. the Hypertension Optimal Treatment [HOT] Study and the Swedish Trial in Old
      Patients with Hypertension-2 [STOP-2]) are close to termination. Final results
      are not yet available, but cardiovascular morbidity appears to be lower than
      expected in the HOT Study, suggesting a positive effect of the CaA-based
      therapeutic regimen. Claims of increased morbidity and mortality from the use of
      CaAs have been clearly refuted by the thorough scrutiny of all available data by
      a committee formed by the World Health Organization and the International Society
      of Hypertension. It can therefore be concluded that the available evidence on the
      use of dihydropyridine CaAs shows that these agents have a beneficial effect on
      morbidity. Whether this effect of CaAs is greater than that obtained with
      conventional therapies, such as diuretics and/or beta-blockers, will be shown by
      the STOP-2 Study, which is expected to be completed in 1998.

PMID- 9660526
TI  - Panel discussion: morbidity and mortality with dihydropyridines--the true
      benefits emerge.

PMID- 9660527
TI  - The technical aspects of biofeedback therapy for defecation disorders.
AB  - Neuromuscular conditioning using biofeedback techniques is a useful method of
      treatment for patients with refractory defecation disorders such as fecal
      incontinence or constipation with obstructive defecation. This article provides
      current perspectives regarding the principles and techniques of performing
      biofeedback therapy. In patients with incontinence, the goals are to improve the
      strength of the anal sphincter, improve sensory perception, and improve
      coordination between the rectum and anal sphincter. In patients with obstructive
      defecation, the goals are to relax the anal sphincter, improve rectoanal
      coordination, and improve sensory perception. Neuromuscular conditioning is an
      instrument-based learning technique. Over the years, several devices and methods
      have become available for performing this training, but no single method is
      either superior or universally popular. The three modalities that are commonly
      used for neuromuscular conditioning are visual, verbal, and audio feedback.
      Ideally, the training program should be customized for each patient based on the
      underlying dysfunction(s). After biofeedback therapy, symptomatic improvement has
      been reported in 70 to 80% of patients with either incontinence or obstructive
      defecation. Recent studies also demonstrated objective improvement in anorectal
      function. In the future, it is likely that simpler and user-friendly, solid-state
      computerized systems may facilitate a wider use of this treatment.

PMID- 9660528
TI  - Common pediatric esophageal disorders.
AB  - Esophageal disorders in children can result in significant morbidity. The most
      common esophageal disorder seen in children is gastroesophageal reflux. Other
      common disorders affecting the esophagus include peptic esophageal strictures,
      esophageal atresia with or without tracheoesophageal fistula, caustic and foreign
      body ingestions, achalasia, and cricopharyngeal achalasia. We discuss what is
      currently known about these common pediatric esophageal disorders with regard to
      pathophysiology, clinical presentation, and diagnostic and treatment strategies.

PMID- 9660529
TI  - Pathophysiology and treatment of hepatorenal syndrome.
AB  - Hepatorenal syndrome is a progressive oliguric renal failure complicating the
      course of advanced cirrhosis and ascites. Significant hemodynamic changes occur
      in these patients consisting of marked systemic arterial vasodilatation and renal
      vasoconstriction. Traditionally, the systemic arterial vasodilatation with the
      consequent underfilling of the effective arterial blood volume has been held
      responsible for the pathogenesis of the renal vasoconstriction. Recent data
      showing a dissociation between the extent of arterial underfilling and the
      development of renal dysfunction in these patients have lead to the proposal of a
      hepatorenal interaction directly causing the renal vasoconstriction, with
      arterial underfilling secondarily contributing further to the renal
      vasoconstriction. Diagnosis of hepatorenal syndrome remains one of exclusion.
      Treatment is largely ineffective except for liver transplantation, which
      unfortunately is not available to all patients because of their short survival.
      Prognosis is very poor once it has developed. Therefore, physicians should be
      alert to avoid precipitating factors in these patients. Recent development of new
      therapies such as the use of a transjugular intrahepatic portosystemic shunt or
      systemic vasoconstrictors appear promising, but their efficacy should be
      evaluated in prospective randomized controlled trials.

PMID- 9660530
TI  - Update on obesity treatment.
AB  - Although the formula for weight control is a simple matter, namely ensure that
      calories consumed equals calories expended, its implementation is a source of
      great frustration for an estimated 85 million Americans. This results in an
      estimated 40 billion dollars spent each year in health and related treatment
      costs. This review outlines the epidemiology, health consequences, and treatment
      of obesity with an emphasis on newer developments in our understanding of the
      etiology of obesity and its treatment.

PMID- 9660531
TI  - Pseudomyxoma peritonei.

PMID- 9660532
TI  - 5-Fluorouracil in colorectal cancer: rationale and clinical results of frequently
      used schedules.
AB  - Colorectal cancer is one of the most frequent cancers in the western world.
      Approximately half of the patients will die of their disease because of
      metastases. The most active cytotoxic agent used to date is 5-fluorouracil (5
      FU). However, clinical responses are achieved only in a minority of patients.
      Based on the current knowledge of the mechanism of action of 5-FU, many attempts
      have been made to improve the clinical results. These include the use of
      biochemical modulators and different methods of administration, and these are the
      subject of this review. Specifically, of five different modulators, i.e.
      leucovorin, methotrexate, interferon-alpha, N-(phosphonacetyl)-L-aspartate and
      trimetrexate glucuronate, the biochemical background and the clinical results
      obtained with these modulators are discussed. In order to get more insight, an
      overview of the 5-FU metabolism has been given. In addition, the different
      methods of systemic administration of 5-FU as well as possible mechanisms
      underlying 5-FU resistance are described.

PMID- 9660533
TI  - Use of granisetron in patients refractory to previous treatment with antiemetics.
AB  - A multicenter, open-label, compassionate-use trial studied the antiemetic
      efficacy and tolerability of granisetron in patients who had failed other
      antiemetic therapies in previous cycles of cytostatic chemotherapy. The
      antiemetics that had been used previously included metoclopramide, dexamethasone
      and ondansetron. A total of 517 patients, 456 of whom had failed other
      antiemetics, were treated in up to 15 successive cycles of chemotherapy. The
      numbers of patients treated in the first six of these cycles were large enough to
      allow the drawing of meaningful conclusions from the results. During that period,
      a complete response was achieved in 53-60% of patients. In addition, antiemetic
      efficacy was sustained throughout these six repeated treatment cycles.
      Granisetron was less effective against high-dose cisplatin chemotherapy than
      against other cytostatic regimens. The treatment was well tolerated--the main
      adverse events reported were headache and constipation; no serious adverse events
      were considered to be attributable to the drug. It is concluded that granisetron
      treatment was effective and well tolerated in patients who had previously failed
      other antiemetic therapies, including treatment with 5-hydroxytryptamine3
      antagonists.

PMID- 9660534
TI  - Granisetron plus methylprednisolone for the control of high-dose cisplatin
      induced emesis.
AB  - This double-blind, double-dummy, randomized study compared the 24 h efficacy and
      safety of granisetron alone (3 mg i.v. over 30 s) or in combination with
      methylprednisolone (250 mg i.v. twice daily) in preventing nausea and vomiting in
      308 patients (254 males) receiving high-dose cisplatin (100 mg/m2 or above) for
      mainly lung, and head and neck cancers. All patients received oral follow-on
      therapy comprising oral granisetron and methylprednisolone during the following 6
      days. Primary efficacy variables were the proportions of complete responses (CR;
      no vomiting, no worse than mild nausea, no rescue and no withdrawal), no vomiting
      and no nausea over the first 24 h following initiation of the cisplatin infusion.
      The two treatment groups were well matched for demographics, cancer site,
      cisplatin dose and duration of infusion. Granisetron plus methylprednisolone was
      significantly more effective than granisetron alone for all primary efficacy
      variables: CR 78 versus 59% (p<0.001), no vomiting 80 versus 61% (p<0.001) and no
      nausea 74 versus 57% (p<0.002). Significantly more patients receiving the
      combination were free of any emetic symptoms (74 versus 54%, p<0.001).
      Significantly fewer patients receiving combination therapy also required rescue
      therapy with i.v. granisetron (12.2 versus 21.7%, p=0.026). During the follow-on
      period, complete response rates varied day by day from 50 to 71%. Both treatments
      were well tolerated, with constipation, abdominal pain and headache as the most
      frequent adverse events.

PMID- 9660535
TI  - Weekly 24 h infusion of high-dose 5-fluorouracil and leucovorin in patients with
      biliary tract carcinomas.
AB  - From October 1995 to June 1997, 19 chemotherapy-naive patients with pathology
      proven locally advanced or metastatic biliary tract carcinomas (BTC) were
      enrolled. The regimen consisted of 5-fluorouracil (5-FU) 2600 mg/m2 and
      leucovorin (LV) 150 mg by weekly 24 h infusion for 6 weeks and followed by a 2
      week break. The treatment was terminated if disease progressed, the patient
      refused or unacceptable toxicity occurred. All patients required a Port-A
      catheter insertion and were treated at outpatient clinics by portable infusion
      pumps. There were 12 males and seven females with a median age of 62 years (range
      45-77). The primary tumor sites were nine intrahepatic cholangiocarcinomas (CC),
      three perihilar CC, one distal BTC and six gallbladder cancers. A total of 179
      chemotherapy sessions were given with a mean of 9.5 (range 2-18). Eighteen
      patients were evaluable for response. The response rates were: 33% (six of 18)
      partial response (PR), 39% (seven of 18) stable disease (SD) and 28% (five of 18)
      progressive disease (PD). All of the patients were evaluable for toxicity. The
      most common toxicities were mild fatigue (nine of 19, 47%), loss of appetite
      (nine of 19, 47%), skin hyperpigmentation (five of 19, 26%) and diarrhea (two of
      19, 11%). Only one patient had grade IV myelotoxicity with sepsis but without
      treatment-related death. The median time to progression was 4 months. The overall
      median survival time was 7.0 months. The median survival time of the PR was not
      reached, SD was 8.0 months and PD 3.5 months. In conclusion, weekly high-dose 5
      FU with LV by 24 h infusion in an outpatient setting for patients with BTC is
      effective, only mildly toxic and deserves further study.

PMID- 9660536
TI  - A crossover study of oral administration of UFT in chronic liver disease:
      comparison of continuous and intermittent schedules.
AB  - This study was aimed at evaluating the tolerance to an intermittently
      administered oral UFT for hepatocellular carcinoma (HCC) with chronic liver
      disease (CLD). Ten patients who had received curative therapy for HCC with CLD
      (Child's classification A or B) were randomly assigned either an intermittent
      schedule (IS), oral administration of UFT (130 mg/m2/b.i.d.) with 2 days rest a
      week, or a continuous schedule (CS), consecutive administration of UFT with the
      same dose. On day 12, the serum concentration of 5-fluorouracil (5-FU) was
      measured. After 2 weeks rest, the patients were switched to the other schedule
      for 10 weeks and the concentration of 5-FU was measured on day 12. The median
      values of the area under the curve (AUC) and maximum concentration (Cmax) of 5-FU
      in IS and CS were 187.7 and 263.2 ng/ml/h, 57.1 and 93.0 ng/ml, respectively.
      Both the AUC and Cmax for IS were significantly lower than those for CS. One IS
      patient had tolerable diarrhea, while three of the CS patients had intolerable
      nausea and one had hemorrhagic gastritis. IS seemed to be a suitable measure for
      CLD.

PMID- 9660537
TI  - Phase II study of i.v. CI-980 in patients with advanced platinum refractory
      epithelial ovarian carcinoma.
AB  - CI-980 is a synthetic mitotic inhibitor that binds to tubulin at the colchicine
      site, inhibiting the polymerization of microtubules and arresting cellular
      division in metaphase. Myelosuppression and neurotoxicity were dose-limiting in
      phase I studies. Sixteen patients with stage III and IV platinum-refractory
      ovarian cancer received 4.5 mg/m2/day of CI-980 as a continuous i.v. infusion for
      72 h, repeated every 3 weeks. Eleven patients had progression and four patients
      had stable disease. One patient (6%; 95% CI 0-25%) achieved a partial response
      after 9 months of treatment which lasted for 27 months. The overall median
      survival was 7 months. Grade 4 granulocytopenia occurred in five patients, with
      two episodes of neutropenic fever. Neurological toxicity was mild with 12
      episodes of transient subclinical recent memory loss documented in four patients
      by specialized neuropsychological evaluations. One patient each had
      hallucinations and mild truncal ataxia, and four patients had mild, reversible
      neurosensory toxicity. One episode of severe hypoxemia and dyspnea occurred in a
      patient with chronic obstructive pulmonary disease. CI-980 has minimal activity
      and is tolerable in a population of heavily pretreated patients with platinum
      refractory ovarian cancer.

PMID- 9660538
TI  - Continuous infusion of low-dose topotecan: pharmacokinetics and pharmacodynamics
      during a phase II study in patients with small cell lung cancer.
AB  - Preclinical schedule dependency suggests that prolonged maintenance of low plasma
      levels of topotecan, a specific inhibitor of the nuclear enzyme topoisomerase I,
      results in optimal antitumor activity. The pharmacokinetics and pharmacodynamics
      of topotecan, administered as single agent in second-line therapy as a continuous
      low-dose infusion for 21 days, were evaluated in nine patients with small cell
      lung cancer (SCLC). Topotecan was administered i.v. as a 21 day continuous
      infusion every 28 days via an ambulatory pump. Dosages ranged from 0.4 to 0.6
      mg/m2/day. Plasma levels of topotecan, the sum of topotecan, and its hydroxy acid
      congener and the N-desmethyl metabolite were determined at 1, 7, 14 and 21 days
      during infusion, using a validated high-performance liquid chromatography method
      with fluorescence detection. Myelosuppression was the most important toxicity.
      All patients experienced anemia, being severe (grade 3/4) in 55% of all courses.
      Other adverse effects were relatively mild and reversible, and included nausea,
      vomiting, diarrhea and fatigue. Three patients achieved a partial response. Mean
      steady-state concentrations of topotecan (C(ss)) in the first course were 0.46+/
      0.17 and 0.47+/-0.19 ng/ml after doses of 0.4 and 0.5 mg/m2/day, respectively.
      Steady-state levels of the total of topotecan and hydroxy acid (C(ss,tot)) were
      1.28+/-0.25 (range 0.93-1.58) and 1.57+/-0.19 (range 1.43-1.70) ng/ml at doses of
      0.4 and 0.5 mg/m2/day, respectively. The percentage of the administered topotecan
      dose excreted in the urine within 24 h was 40+/-14 and 1.2+/-1.0% for total
      topotecan and N-desmethyltopotecan, respectively. During the second course,
      C(ss,tot) was significantly higher (p=0.032, paired t-test), which suggests
      altered topotecan disposition. A sigmoidal relationship was found between
      C(ss,tot) and the percent decrease in platelets (r=0.76, p=0.018). We conclude
      that topotecan administered as a 21 day continuous low-dose infusion has activity
      as single-agent, second-line therapy in patients with SCLC. There was
      considerable interpatient and intrapatient variability in systemic exposure to
      topotecan. Differences in organ function might contribute to this variation.
      Serum aspartate aminotransferase and albumin levels were predictive of topotecan
      pharmacokinetics.

PMID- 9660539
TI  - Vorozole (R83842) in the treatment of postmenopausal advanced breast cancer:
      relationship of serum levels of vorozole and clinical results (a study of the
      EORTC Breast Cancer Cooperative Group).
AB  - The new non-steroidal aromatase inhibitor vorozole (R83842) was administered
      orally at a single daily dose of 2.5 mg to 27 postmenopausal women with advanced
      breast cancer in a phase II trial as second-line endocrine treatment. The
      observed objective response rate of 30% and good tolerability of the drug confirm
      other recent reports. Endocrine determinations during 6 months of treatment
      demonstrated reduction of serum estrogens: estrone sulfate by more than 60%,
      estrone by 30-40%, but estradiol by only 10-20%. The ratios of serum
      androstenedione/estrone and testosterone/estradiol increased significantly,
      consistent with the inhibition of peripheral aromatase activity. Levels of
      progesterone, 17-alpha-hydroxyprogesterone, cortisol, dehydroepiandrosterone
      sulfate, androstenedione and aldosterone remained normal, indicating no
      interference with adrenocortical steroid synthesis. A general lack of correlation
      between the observed serum concentrations of vorozole and its effect on hormone
      serum levels or clinical response was found. This suggests that the determination
      of such serum levels gives a poor impression of the unambiguous anti-tumor
      activity of vorozole which may well have its main effect with the tumor tissue
      itself. The present results are in support of aromatase inhibition, but the
      possibility of an additional effect on the sulfation of estrogens merits further
      investigation.

PMID- 9660540
TI  - Phase II study of continuous 120 h infusion of mitomycin C as salvage
      chemotherapy in patients with progressive or rapidly recurrent colorectal cancer.
AB  - We evaluated the therapeutic activity and safety of continuously infused
      mitomycin C in patients with metastatic colorectal cancer who had recurred (less
      than 3 months) or progressed following first- or second-line 5-fluorouracil-based
      chemotherapy. Treatment consisted of mitomycin C 20 mg/m2 i.v. given over 120 h
      (5 days) followed by a 3 week rest period. Fifty-two consecutively enrolled
      patients were assessable for toxicity and 49 for response evaluation (three
      patients evaluable but not measurable), completing at least one full course of
      chemotherapy. Previous chemotherapy regimens consisted of bolus 5
      fluorouracil/folinic acid (5-FU/FA) (Machover) n=26 (50%) or continuous (24 h) 5
      FU+/-FA+/-interferon n=26 (50%). Forty-two percent of patients had received one
      previous chemotherapy regimen and 58% more than one. One partial remission (2%)
      lasting 7 months and 11 disease stabilizations (23%) with a median duration of
      3.2 months (range 1-8) were achieved in 49 patients. Median survival time since
      start of mitomycin C was 4.7 months (1.2-28.1) resulting in a 6 month survival
      rate of 36%. The progression-free interval was 10 weeks (range 4-36). Delayed and
      cumulative thrombo- and leukocytopenia (WHO grade III/IV) were observed in 19 and
      6%, and anemia in 2% of patients. WHO grade I/IV mucositis, diarrhea and
      fever/infection occurred each in 6% of patients. Treatment delays and dose
      reductions were necessary in 11 (21%) and 21 (40%) patients, respectively. In
      three cases treatment was stopped due to cumulative thrombocytopenia (6%).
      Continuous infusion of single-agent mitomycin C displays modest activity in
      heavily pretreated 5-FU refractory colorectal cancer patients combined with a low
      toxicity level.

PMID- 9660541
TI  - Mitomycin C-related hemolytic uremic syndrome in cancer patients.
AB  - In rare cases mitomycin C (MMC) may induce cancer-associated hemolytic uremic
      syndrome, which is characterized by hemolytic anemia, thrombocytopenia and
      progressive renal failure. Treatment possibilities of this multisystem disease up
      to now remain disappointing. We report a case of MMC-related hemolytic uremic
      syndrome, and discuss the etiologic parameters, clinical aspects, prognosis and
      treatment modalities of this severe syndrome.

PMID- 9660542
TI  - Effects of 1,2-naphthoquinones on human tumor cell growth and lack of cross
      resistance with other anticancer agents.
AB  - The sensitivity of human tumor and rat prostate tumor cells to a series of
      naphthoquinones, including tricyclic compounds of the beta-lapachone and dunnione
      families as well as 4-alkoxy-1,2-naphthoquinones, was evaluated. To better
      understand the mechanism of cytotoxicity of 1,2-naphthoquinones, the roles of
      various resistance mechanisms including P-glycoprotein, multidrug resistant
      associated protein, glutathione (GSH) and related enzymes, altered topoisomerase
      activity, and overexpression of genes that control apoptosis (bcl-2 and bc-xL)
      were studied. MCF7 cells were most sensitive to the naphthoquinones with IC50
      values ranging from 1.1 to 10.8 microM, as compared to 2.5 to >32 microM for HT29
      human colon, A549 human lung, CEM leukemia and AT3.1 rat prostate cancer cells.
      MCF7 ADR cells, selected for resistance to adriamycin (ADR), displayed cross
      resistance to the tricyclic 1,2-naphthoquinones. Drug efflux via a P-glycoprotein
      mechanism was ruled out as a mechanism of resistance to 1,2-naphthoquinones,
      since KB-V1 cells expressing high levels of P-glycoprotein and the KB-3.1 parent
      line were equally sensitive to these compounds. Any resistance of the tricyclic
      naphthoquinones noted in ADR-resistant cells appeared to relate to the GSH redox
      cycle and could be circumvented by exposure to buthionine sulfoximine or by
      changing the structure from a tricyclic derivative to a 4-alkoxy-1,2
      naphthoquinone. The 1,2-naphthoquinones were found to be cytotoxic against CEM/VM
      1 and CEM/M70-B1 cells that were selected for resistance to teniposide or
      merbarone, respectively. In addition, cells overexpressing bcl-2 or bcl-xL
      proteins were as sensitive to 1,2-naphthoquinones as were control cells. Because
      of their effectiveness in drug-resistant cells, these agents appear to hold
      promise as effective chemotherapeutic agents.

PMID- 9660543
TI  - Characterization of multidrug resistance and monitoring of tumor response by
      combined 31P and 1H nuclear magnetic resonance spectroscopic analysis.
AB  - A combined 31P and 1H nuclear magnetic resonance (NMR) spectroscopic study was
      carried out in drug-sensitive and adriamycin- and mitoxantrone-resistant P388
      murine leukemic cells. Typical spectral changes characteristic of multidrug
      resistance were observed in resistant cells compared to drug-sensitive cells.
      Quantitative comparison of phosphate metabolites ATP, phosphocreatine,
      phosphomonoesters and phosphodiesters revealed a significant alteration in the
      metabolism of resistant cells. The elevated levels of energy metabolites
      supported the energy-dependent process of drug efflux in resistant cells. An
      increased rate of glycolysis in resistant cells as indicated by the elevated
      lactate level further supported this. The near total loss of energy metabolites
      and marked decrease in phospholipid metabolites in sensitive cells upon treatment
      with drug compared to unaltered metabolite levels in resistant cells suggested
      that the spectral changes can reveal the subtle differences in tumor response
      between drug-sensitive and -resistant cells. The results substantiate the
      potential of this non-invasive method to characterize the multidrug resistance
      phenotype and monitor tumor response.

PMID- 9660544
TI  - Combination of cisplatin-procaine complex DPR with anticancer drugs increases
      cytotoxicity against ovarian cancer cell lines.
AB  - DPR, cis-diamminechloro-[2-(diethylamino)ethyl 4-amino-benzoate, N4]
      chlorideplatinum(II) monohydrochloride monohydrate, is a newly developed water
      soluble platinum compound which possess minimal cross-resistance to cisplatin and
      shows relatively less side effects. In an attempt to establish whether the
      combination of DPR with other conventional anticancer drugs would be of any
      benefit we assessed in vitro the cytotoxic effects of combinations of DPR with
      the antimetabolites 5-fluorouracil (5-FU) and methotrexate (MTX), the alkylating
      agents mitomycin C (MMC) and cisplatin, the antimicrotubule agent taxol (TAX),
      and the intercalating agent of the anthracycline group doxorubicin (DOX) on
      murine M5076 ovarian reticulosarcoma and human A2780 ovarian carcinoma cells.
      These agents were selected because of their common use in the clinic and because
      they represent four distinct categories of antineoplastic mechanisms. Cells were
      incubated for 72 h in the presence of single or combined drugs, and the cytotoxic
      effect was determined by the MTT assay. The analysis of combination treatment was
      made by the isobole method. In human A2780 cells, an overall synergy was found
      for DPR combined with 5-FU, DOX and cisplatin. Synergistic effects were also
      observed for most combinations with MTX or MMC. A DPR concentration-dependent
      additivity and antagonism was seen at the highest MTX concentration (1 microM),
      while additive effects were observed for the combined treatments of DPR and low
      concentrations of MMC (0.008 and 0.0016 microM). Additive effects were also
      observed for the association of DPR and TAX over most combinations tested. In
      murine M5076 cells, synergism was the prevailing result observed when DPR was
      combined with 5-FU, DOX, MMC or cisplatin. When administered together with MTX we
      observed additivity over most combinations tested. These findings suggest that
      DPR, when simultaneously administered with standard anticancer agents, may be
      advantagious for cytokilling.

PMID- 9660545
TI  - The one-ring open hydrolysis intermediates of the cardioprotective agent
      dexrazoxane (ICRF-187) do not inhibit the growth of Chinese hamster ovary cells
      or the catalytic activity of DNA topoisomerase II.
AB  - Dexrazoxane (ICRF-187), which is clinically used to reduce doxorubicin-induced
      cardiotoxicity, has growth inhibitory properties through its ability to inhibit
      the catalytic activity of DNA topoisomerase II. Because the bisdioxopiperazine
      dexrazoxane undergoes significant ring-opening hydrolysis under physiological
      conditions to form two one-ring open hydrolysis intermediates, a study was
      undertaken to determine if these two intermediates had either any growth
      inhibitory or topoisomerase II inhibitory effects. Neither of the one-ring open
      intermediates exhibited growth inhibitory effects towards Chinese hamster ovary
      cells nor were they able to inhibit topoisomerase II. Thus, it was concluded that
      only intact dexrazoxane is able to inhibit the catalytic activity of
      topoisomerase II.

PMID- 9660546
TI  - Modulation of cisplatin toxicity in blood platelets by glutathione depletion.
AB  - The effect of a specific inhibitor of gamma-glutamylcysteine synthetase, L
      buthionine sulfoximine (BSO), on the action of cisplatin in pig blood platelets
      was investigated. We show that the effect of BSO, blocking glutathione (GSH)
      synthesis, on depletion of GSH level in platelets was time and dose dependent
      (p<0.05). Exposure of blood platelets to BSO reduced not only the cellular GSH
      content, but diminished also cytotoxicity effects of cisplatin on platelets.
      Cytotoxic effects of cisplatin were determined by the extent of oxidative stress
      in these cells, i.e. lipid peroxidation expressed as thiobarbituric acid reactive
      substances and oxygen free radicals (superoxide anion). The obtained results
      confirm that the intracellular level of GSH plays an important role in the action
      of cisplatin on blood platelets.

PMID- 9660547
TI  - Evaluation of extra- and intracellular apparent diffusion in normal and globally
      ischemic rat brain via 19F NMR.
AB  - The biophysical mechanism(s) underlying diffusion-weighted MRI contrast following
      brain injury remains to be elucidated. Although it is generally accepted that
      water apparent diffusion coefficient (ADC) decreases after brain injury, it is
      unknown whether this is associated with a decrease in intracellular or
      extracellular water displacement, or both. To address this question, 2-[19F]luoro
      2-deoxyglucose-6-phosphate (2FDG-6P) was employed as a compartment-specific
      marker in normal and globally ischemic rat brain. Through judicious choice of
      routes of administration, 2FDG-6P was confined to the intra- or extracellular
      space. There was no statistical difference between intra- and extracellular 2FDG
      6P ADCs in normal or in globally ischemic brain (P > 0.16), suggesting that water
      ADCs in both compartments are similar. However, ischemia did result in a 40% ADC
      decrease in both compartments (P < 0.001). Assuming that 2FDG-6P reflects water
      motion, this study shows that water ADC decreases in both spaces after ischemia,
      with the reduction of intracellular water motion being the primary source of
      diffusion-weighted contrast.

PMID- 9660548
TI  - An optimal and efficient new gridding algorithm using singular value
      decomposition.
AB  - The problem of handling data that falls on a nonequally spaced grid occurs in
      numerous fields of science, ranging from radio-astronomy to medical imaging. In
      MRI, this condition arises when sampling under time-varying gradients in
      sequences such as echo-planar imaging (EPI), spiral scans, or radial scans. The
      technique currently being used to interpolate the nonuniform samples onto a
      Cartesian grid is called the gridding algorithm. In this paper, a new method for
      uniform resampling is presented that is both optimal and efficient. It is first
      shown that the resampling problem can be formulated as a problem of solving a set
      of linear equations Ax = b, where x and b are vectors of the uniform and
      nonuniform samples, respectively, and A is a matrix of the sinc interpolation
      coefficients. In a procedure called Uniform Re-Sampling (URS), this set of
      equations is given an optimal solution using the pseudoinverse matrix which is
      computed using singular value decomposition (SVD). In large problems, this
      solution is neither practical nor computationally efficient. Another method is
      presented, called the Block Uniform Re-Sampling (BURS) algorithm, which
      decomposes the problem into solving a small set of linear equations for each
      uniform grid point. These equations are a subset of the original equations Ax = b
      and are once again solved using SVD. The final result is both optimal and
      computationally efficient. The results of the new method are compared with those
      obtained using the conventional gridding algorithm via simulations.

PMID- 9660549
TI  - Arterial phase carotid and vertebral artery imaging in 3D contrast-enhanced MR
      angiography by combining fluoroscopic triggering with an elliptical centric
      acquisition order.
AB  - Arterial-phase three-dimensional (3D) contrast-enhanced MR angiograms of the
      carotid and vertebral arteries from their origins through the carotid
      bifurcations were obtained in 20 patients using acquisition times over 30 sec by
      using an MR fluoroscopy-triggered pulse sequence with elliptical centric view
      order. The typical pixel size was 0.8 mm (x) x 1.6 mm (y) x 1.5 mm (z), and 32-48
      coronal slices were acquired. The fluoroscopic monitoring of bolus arrival was
      effective in 18 of the 20 cases; two failures were attributed directly to a poor
      choice of RF coil. To exploit peak arterial-to-venous contrast, the central 3D
      views were acquired first in the most compact time period possible for the given
      TR. For the 18 successfully triggered cases, arterial-phase 3D images were
      obtained with excellent venous suppression as demonstrated by an average internal
      jugular vein to common carotid signal enhancement ratio of only 0.05 +/- 0.04.

PMID- 9660550
TI  - Proton NMR spectroscopy of solvent-saturable resonances: a new approach to study
      pH effects in situ.
AB  - It is shown that the effect of pH changes can be measured in proton NMR spectra
      through the pH sensitivity of the signal intensities of metabolite protons
      exchanging with water. To observe this phenomenon, pulse sequences must be used
      that can sensitively observe these exchangeable protons under physiological
      conditions, which is achieved by avoiding magnetization transfer signal losses
      due to water saturation for solvent suppression purposes. These methods provide
      an order-of-magnitude enhancement of many signals between 5 and 10 ppm,
      containing both N-bound protons as well as aromatic C-H protons coupled to them,
      the intensity of which is influenced by exchange-relayed saturation. As a first
      application, the effects of pH change on these resonances are studied ex vivo
      (perfused cells) and in vivo (cat brain).

PMID- 9660551
TI  - Magnetic resonance microimaging for noninvasive quantification of myocardial
      function and mass in the mouse.
AB  - The purpose of this work was to develop high-resolution cardiac magnetic
      resonance imaging techniques for the in vivo mouse model for quantification of
      myocardial function and mass. Eight male mice were investigated on a 7-Tesla MRI
      scanner. High-quality images in multiple short axis slices (in-plane resolution
      117 microm2, slice thickness 1 mm) were acquired with an ECG-gated cine sequence.
      Left ventricular end-diastolic and end-systolic volumes and mass were calculated
      from segmented slice volumes. There was precise agreement of left ventricular
      mass determined ex vivo and by MRI. Intraobserver (5%) and interobserver (5%)
      variability of in vivo MR measurements were low.

PMID- 9660552
TI  - A spiral volume coil for improved RF field homogeneity at high static magnetic
      field strength.
AB  - Biological samples have a high dielectric constant that can shorten RF
      wavelengths by a factor of 8 relative to the vacuum. At high field strengths,
      finite wavelength effects within larger samples are the dominant cause of RF
      field nonuniformity. A coil design is presented that can reduce and even
      eliminate this inhomogeneity; 4-T images in phantoms and in the head of a normal
      volunteer are presented, which demonstrate improved homogeneity relative to a
      standard coil. This coil design should aid in realizing the potential advantages
      of imaging large samples at high field strengths.

PMID- 9660553
TI  - Magnetic field changes in the human brain due to swallowing or speaking.
AB  - Variations in the magnetic field in the human brain caused by the processes of
      swallowing or speaking are measured. In both processes, motion of the pharyngeal
      muscles, especially the tongue and jaw, alter the susceptibility-induced magnetic
      field distribution at the brain slice being imaged. This leads to image warping,
      compromising the analysis of a time series of images, such as in functional
      magnetic resonance imaging (fMRI). These dynamic changes are assessed by
      acquiring a time series of images using a gradient-echo asymmetric-spin-echo
      sequence (GREASE), a technique in which two images are acquired for each
      excitation--one during the gradient echo, and one during the latter part of the
      spin echo. The NMR phase difference between the two images is a measure of the
      magnetic field distribution. A series of brain images, acquired with this
      sequence while the subject either swallows or speaks, indicated negative magnetic
      field changes of up to 0.087 ppm in the inferior region of the brain for both
      speaking and swallowing, and in some speech, additional positive changes of up to
      0.056 ppm in the frontal region of the brain were indicated.

PMID- 9660554
TI  - Hyperpolarized 3He NMR lineshape measurements in the live guinea pig lung.
AB  - Spatially localized lineshapes of hyperpolarized (HP) 3He in guinea pig lungs
      have been measured in vivo. Three different axial slice locations, each
      containing different compositions of airway sizes and orientations, were studied.
      Gas peaks from major bronchi (2 ppm) and alveoli (-2 ppm) were distinguished. The
      gas phase spectra show structural features that are a result of frequency shifts
      caused by bulk magnetic susceptibility. For a given slice, the spectral
      lineshapes reflect the airway composition within the slice location, according to
      theory. The peak assignments given here also agree with previous studies done by
      Wagshul et al. with HP 129Xe. At each of the slice locations, data were acquired
      during two phases of the breathing cycle, resulting in a relative frequency shift
      of approximately 0.3 ppm in the superior slices. Spectra obtained over a number
      of breaths show the dynamics of the gas buildup in the lung and provide further
      evidence supporting the peak assignments.

PMID- 9660555
TI  - In vivo proton magnetic resonance spectroscopy of the medial temporal lobes of
      subjects with combat-related posttraumatic stress disorder.
AB  - Recent findings using volumetric MRI techniques have revealed that patients with
      combat-related and noncombat-related posttraumatic stress disorder (PTSD) have
      reductions in right hippocampal volume. Twenty-one veterans with PTSD and eight
      age-matched control veterans were studied using proton magnetic resonance
      spectroscopy to test the hypothesis that the N-acetyl-L-aspartic acid/creatine
      (NAA/Cr) ratio would be decreased in the right medial temporal lobe structures of
      patients with PTSD compared to controls. Patients with PTSD displayed
      significantly lower NAA/Cr ratio for the right medial temporal lobe relative to
      the left (P < or = 0.011). Patients with PTSD also had lower NAA/Cr in right
      medial temporal lobe (P < or = 0.013) and lower choline/Cr in left medial
      temporal lobe (P < or = 0.030) compared to control subjects. Because NAA is
      regarded as an indicator of neuronal density, this finding suggests that the
      neuronal density of right-sided medial temporal structures in patients with
      combat-related PTSD may be decreased.

PMID- 9660556
TI  - A systematic study of the lactate lineshape in PRESS-localized proton
      spectroscopy.
AB  - J-coupled resonances such as lactate exhibit complex behavior in PRESS-localized
      spectroscopy. Polarization transfer effects due to nonideal slice profiles can
      lead to substantial errors in quantification unless recognized. In this work, it
      is shown how these effects can be predicted in a systematic way given the
      sequence timing and the RF pulse envelopes. Experimental results are presented to
      highlight the problems of working at the popular echo time of 2/J.

PMID- 9660557
TI  - Integrated analysis of diffusion and relaxation of water in blood.
AB  - Diffusion and T2 relaxation of water both inside and outside red blood cells
      (RBCs) in human blood were investigated using a hybrid NMR pulse sequence to
      obtain a more quantitative understanding of the diffusion and relaxation behavior
      of water in paramagnetic-doped blood samples. The data were analyzed by both
      examining the relaxation properties of the system after each diffusion weighting
      and looking at the diffusion properties at each echo time. The results illustrate
      how diffusion-sensitizing gradients affect the T2 spectra of blood and how
      relaxation weighting changes the curvature of the diffusion curves, thereby
      demonstrating the close coupling between diffusion and T2 relaxation. A three
      pool model, consisting of RBCs, plasma, and macromolecular protons, was used to
      model the data from the diffusion-relaxation hybrid experiments. The model was
      found to describe all the characteristic features of the experimental data well
      and was used to evaluate the approximations involved in the conventional analysis
      methods and elucidate the nature of the relaxing and diffusing components.
      Compared with the separate diffusion and relaxation experiments, the diffusion
      relaxation hybrid experiments are less time-consuming, result in better parameter
      determinations, and may be useful in analyzing diffusion-T2 coupling in tissues
      with more complicated multiexponential T2 behavior.

PMID- 9660558
TI  - Measurement of perfusion rate in human melanoma xenografts by contrast-enhanced
      magnetic resonance imaging.
AB  - Reliable methods based on MRI for measurement of the perfusion rate in human
      tumors are highly warranted. Tumors of two amelanotic human melanoma xenograft
      lines were subjected to dynamic 1H MRI after i.v. administration of gadopentetate
      dimeglumine (Gd-DTPA). The aim was to investigate to what extent different
      perfusion parameters determined from the Gd-DTPA kinetics, i.e., the initial
      uptake rate, the maximal uptake, the decay rate, and the perfusion rate
      calculated by use of the Kety equation, can be used as a reliable estimate of
      tumor perfusion rate. Each parameter was calculated in dual; one calculation was
      based on relative signal intensity increase (RSII) in T1-weighted MR images and
      the other on Gd-DTPA concentration determined from the images. The perfusion
      parameters were compared with the perfusion rates determined from measurement of
      tumor uptake of 86Rb or [14C]iodoantipyrine. The results showed that reliable
      estimates of tumor perfusion rate can be achieved from analysis of Gd-DTPA
      kinetics by use of the Kety equation. Gd-DTPA kinetics based on concentration
      might be used to achieve reliable estimates of absolute tumor perfusion rate,
      whereas reliable estimates of the relative perfusion rate might also be achieved
      from Gd-DTPA kinetics based on RSII. The initial uptake rate, the maximal uptake,
      and the decay rate of Gd-DTPA, however, are not reliable estimates of tumor
      perfusion rate, mainly because these parameters are highly influenced by the
      tumor extracellular volume fraction in addition to the perfusion rate.

PMID- 9660559
TI  - Dynamic k-space filling for bolus chase 3D MR digital subtraction angiography.
AB  - A bolus chase three-dimensional (3D) MR digital subtraction angiography (MRDSA)
      technique was implemented using dynamic k-space filling. This technique permits
      rapid 3D arterial imaging of the entire lower extremity at multiple stations
      using a single intravenous injection. Image acquisition at the first (most
      proximal) station starts from the edge of k-space and ends in the center of k
      space (edge-center order). Image acquisition for middle stations starts from the
      edge of k-space, arrives at the center of k-space at the middle of data
      acquisition, and ends at the edge of k-space (edge-center-edge order). Image
      acquisition for the last station starts from the center of k-space and ends at
      the edge of k-space (center-edge order). This dynamic k-space filling minimizes
      contrast dose and motion artifacts. Bolus chase 3D MRDSA was performed on four
      normal volunteers and three patients using a multiple-phase 3D fast gradient-echo
      sequence, 25-ml gadolinium dose, and a prototype stepping table. Total bolus
      chase 3D acquisition time was 46 s. Mask subtraction using both complex and
      magnitude subtraction was performed. Complex subtraction was found to be
      necessary for proper delineation of arteries below the aortic bifurcation.
      Diagnostic results were consistently obtained for all subjects.

PMID- 9660560
TI  - Interactive coronary MRI.
AB  - The acquisition of complete three-dimensional (3D), segmented gradient-echo data
      sets to visualize the coronary arteries can be both time consuming and sensitive
      to motion, even with use of multiple breath-holding or respiratory gating. An
      alternate hybrid approach is demonstrated here, in which real-time interactive
      imaging is first used to locate an optimal oblique coronary scan plane. Then, a
      limited number of contiguous slices are acquired around that plane within a
      breath-hold with use of two-dimensional (2D) segmented gradient-echo imaging.
      Dual inversion nulling is used to suppress fat and myocardium. Finally, if
      needed, a limited reformat of the data is performed to produce images from
      relatively long sections of the coronaries. This approach yields relatively rapid
      visualization of portions of the coronary tree. Several different methods are
      compared for interactively moving the scan plane.

PMID- 9660561
TI  - Signal undershoots following visual stimulation: a comparison of gradient and
      spin-echo BOLD sequences.
AB  - Gradient-echo (GRE) and spin-echo (SE) EPI BOLD sequences were used to quantitate
      the effect of visual stimulation. Both sequences showed a positive BOLD response
      during stimulation and a negative BOLD response in the interstimulation
      intervals. The relaxation rate changes during stimulation were larger for the GRE
      sequence than for the SE sequence, whereas in the interstimulation intervals they
      were not significantly different. In both cases, the ratio of the GRE/SE
      relaxation rate changes were consistent with BOLD effects in larger vessels
      despite the well-known lower sensitivity of the SE sequence to the extravascular
      component of the BOLD effect in larger vessels. The most probable explanation of
      this result is that a significant fraction of the observed changes originated
      from the intravascular component of the BOLD effect. The SE sequence depicted
      smaller areas of activation than the GRE sequence with more than 85% of the
      pixels being depicted as significant by the SE sequence being also significant in
      the GRE activation maps. However, for the reverse comparison, an overlap of only
      35% was observed, with many of the strongly correlated GRE pixels showing weak
      correlations in the corresponding SE activation image. Our results, together with
      the fact that signal undershoots have not been observed by groups using MR
      sequences that measure absolute flow changes for similar stimulation paradigms,
      suggest that the undershoot may be due to alterations in the blood volume and/or
      hematocrit during stimulation that normalize at a slower rate than the changes in
      blood flow after the cessation of the stimulation, leading to a poststimulation
      signal undershoot.

PMID- 9660562
TI  - MR microscopy of transgenic mice that spontaneously acquire experimental allergic
      encephalomyelitis.
AB  - Pathology of fixed spinal cords from transgenic mice with a myelin basic protein
      (MBP) specific T cell receptor was investigated. These mice spontaneously acquire
      the demyelinating disease experimental allergic encephalomyelitis (EAE). Several
      complementary imaging modalities, all on the same tissues, were used to visualize
      lesions; these included high-field (11.7-T) microscopic diffusion tensor imaging
      (DTI), T2*-weighted imaging, and optical microscopy on histological sections.
      Lesions were predominantly in white matter around meninges and vasculature and
      appeared hyperintense in anatomical images. DTIs showed reduced diffusion
      anisotropy in the same hyperintense regions, consistent with inflammation and
      edema. Histology in the same tissues exhibited the characteristic pathology of
      EAE. Two techniques for visualizing the effective diffusion tensor fields are
      presented, which display direction, organization, and integrity of neuronal
      fibers. It is shown that DTI offers intriguing possibilities for visualizing
      axonal organization and lesions within white matter.

PMID- 9660563
TI  - Gadolinium-bearing red cells as blood pool MRI contrast agents.
AB  - Human and rat red blood cells (RBCs) were loaded with gadolinium DTPA dimeglumine
      using an osmotic pulse technique to create a blood pool contrast agent for MRI.
      The resulting packed red cells contained 30.9 +/- 3.3 (1 SD) mmol Gd/liter for
      humans and 24.7 +/- 3.5 (1 SD) mmol Gd/liter for rats. Longitudinal relaxation
      rate constant of human RBCs increased from 2.0 +/- 0.1 to 145.6 +/- 36.2 s(-1);
      the transverse relaxation rate constant increased from 6.8 +/- 1.2 to 562 +/- 410
      s(-1). For rat RBCs, R1 increased from 1.45 +/- 0.15 to 84.8 +/- 23.9 s(-1); R2
      increased from 7.1 +/- 0.64 to 247 +/- 158 s(-1). Affinity for oxygen was
      slightly reduced (control P50 = 22.3 +/- 2.3 versus experimental P50 = 27.3 +/-
      1.3, P < 0.01), as was mechanical deformability. No drop in relaxivities was seen
      after 5 days of storage. The apparent volume of distribution was 0.0164 +/- 0.003
      liter/kg, biologic half-life 4.38 +/- 0.34 h, and total plasma clearance 0.003 +/
      0.0006 liter/kg/h. Compared with Gd-DTPA "free" in the plasma, tissue
      enhancement from RBCs was initially lower but was much prolonged. Preparation is
      simple enough to be reproduced by most laboratories.

PMID- 9660564
TI  - A new semiautomated, three-dimensional technique allowing precise quantification
      of total and regional cerebellar volume using MRI.
AB  - A new method was developed to measure total and regional cerebellar volumes using
      MRI. Previously, the volumes of the cerebellum and its substructure had been
      studied planimetrically. The new method uses three-dimensional semiautomated
      volumetry with focus on reliability and performance. The method consists of a
      manual presegmentation using landmark-adjusted planes followed by region-growing
      segmentation and calculation of volume. The cerebellum is partitioned into 11
      regions defined by planes, which are adjusted for internal cerebellar landmarks
      (three radial regions inside the vermis that extend into the medial hemisphere
      (one-fourth of the transverse diameter of the hemisphere); one region in the
      lateral hemisphere (remaining three-fourths)). Forty-six healthy volunteers were
      examined and the effects of age, gender, and symmetry were estimated. Shrinkage
      in the vermis (especially anterior superior compartment) was marked. Age effects
      diminished laterally and were not observed in the lateral hemisphere. Age effects
      on the total cerebellar volume were marginal. Effects of gender and symmetry were
      nonsignificant. Technique and results are discussed and related to methods and
      findings of others.

PMID- 9660565
TI  - Small particles of fusinite and carbohydrate chars coated with aqueous soluble
      polymers: preparation and applications for in vivo EPR oximetry.
AB  - The development of oxygen-sensitive paramagnetic materials is being pursued
      actively because of their potential applications in in vivo EPR oximetry. Among
      these materials, several charcoals and carbohydrate chars are of special interest
      because of their desirable EPR properties: high sensitivity of the EPR linewidth
      to the partial pressure of oxygen, simple EPR spectra, and high spin density.
      Their potential use in humans, however, is limited by the need to demonstrate
      that they will not lead to deleterious effects. A strategy was used to optimize
      the biocompatibility of the oxygen-sensitive materials by decreasing the size of
      the particles and coating them with suspending or surfactive agents such as
      arabic gum, poloxamer (Pluriol 6800), and polyvinylpyrrolidone. The coated
      particles of a carbohydrate char and fusinite were characterized in vitro for
      their size, stability, and pO2 sensitivity. The feasibility of performing pO2
      measurement was examined in vivo by inducing ischemia in the gastrocnemius muscle
      of mice. The use of arabic gum for coating the fusinite particles preserved the
      pO2 sensitivity in vivo, whereas the other surfactive agents led to a loss of the
      pO2 sensitivity in vivo. Small particles of fusinite coated by arabic gum and
      intravenously administered to mice accumulated in the liver, whereas the uncoated
      fusinite was toxic when injected intravenously due to the large size and
      aggregation of the particles. Histological studies performed up to 6 months after
      the injection in muscles of mice did not indicate any toxicity from the materials
      used in the present study.

PMID- 9660566
TI  - Anisotropically weighted MRI.
AB  - The intensity of an isotropically weighted MR image is proportional to a
      rotationally invariant measure of bulk diffusion, Trace(D) (where D is the
      effective diffusion tensor). Such images can be acquired from as few as two
      diffusion-weighted images (DWIs). Analogously, the intensity of an
      anisotropically weighted MR image is proportional to a rotationally invariant
      measure of diffusion anisotropy derived from D, such as the variance of the
      principal diffusivities of D. By using linear algebra, we show that to produce an
      anisotropically weighted MR image requires acquiring at least seven DWIs, which
      is also the minimum number of DWIs sufficient to estimate the entire diffusion
      tensor, as well as the T2-weighted amplitude image, A(b = 0), in each voxel. A
      general mathematical framework for constructing isotropically weighted and
      anisotropically weighted MR images is also provided.

PMID- 9660567
TI  - The effect of sample freezing on proton magic-angle spinning NMR spectra of
      biological tissue.
AB  - Magic-angle spinning (MAS) has recently been shown to enhance spectral resolution
      in NMR examinations of intact biological tissue ex vivo. This work demonstrates
      that freezing certain tissue samples before examination by 1H MAS NMR can have a
      marked effect on their spectra. Spectra of rat kidney after freezing in liquid
      nitrogen, compared with spectra before freezing, showed a significant increase in
      signal intensities from alanine (>100%), glutamine (>40%), and glycine (>100%),
      and a decrease in signals assigned to lipids and other macromolecules. Some
      resonances--such as from leucine, valine, isoleucine, and aspartate--only became
      visible after freezing the tissue. These observations suggest that low
      temperature storage of tissue necropsies or biopsies might affect the results of
      a MAS NMR analysis, possibly resulting in the misinterpretation of metabolite
      changes to pathogen or disease effects.

PMID- 9660569
TI  - Extending Medicare's protection.

PMID- 9660568
TI  - 29Si imaging of silicone breast implants and intraocular silicone oil.
AB  - Silicon-29 (29Si) imaging was investigated as a potential imaging modality for
      monitoring silicone prostheses in humans. The 29Si relaxation times of several
      silicone gels were measured and found to average T1 = 21.2 +/- 1.5 s and T2 = 207
      +/- 40 ms, with no significant difference between virgin and explanted gels. A
      single-shot half-Fourier rapid acquisition with relaxation enhancement (RARE) and
      a refocused gradient-echo sequence were used for acquiring 29Si images with 5 x 5
      mm2 resolution and no slice selection. Three volunteers with silicone-gel-filled
      breast implants and one subject with an intraocular silicone oil injection were
      thus examined in a total acquisition time of 10-15 min per image. On all 29Si
      images, the shape of the silicone object was well depicted. Although at present,
      conventional proton images are superior in resolution and signal-to-noise ratio,
      29Si imaging has the advantage of optimal specificity, since only the silicone
      itself is visible.

PMID- 9660570
TI  - Pancreas transplants: for whom?

PMID- 9660571
TI  - Looking beyond first-ever stroke incidence.

PMID- 9660572
TI  - Realism or nihilism in bowel cancer follow-up?

PMID- 9660573
TI  - A ghostly crew.

PMID- 9660574
TI  - Lancet fellowships 1998/99.

PMID- 9660575
TI  - Venous thromboembolism and cancer.
AB  - BACKGROUND: Although cancer has been clearly associated with venous
      thromboembolism (VTE), many aspects of this relation are poorly understood,
      including the cancer sites most affected and the cancer risk during long-term
      follow-up. To clarify these relations, we carried out a large, population-based
      analysis of VTE and cancer risk. METHODS: Using the Swedish Inpatient Register
      and linkage to the nationwide Cancer Registry, we assessed cancer incidence
      during 1989 among 61,998 patients without a previous cancer diagnosis admitted to
      hospital between 1965 and 1983 for VTE. To measure possible increases in cancer
      risk, we computed standardised incidence ratios (SIRs) using Swedish national
      cancer rates for the period of the study. FINDINGS: At the time of thromboembolic
      admission or during the first year of follow-up, 2509 cancers were diagnosed (SIR
      4.4, 95% CI 4.2-4.6) [corrected]. The SIR for polycythaemia vera was 12.9 (8.6
      18.7), and the SIRs for cancers of the liver, pancreas, ovary, and brain, and for
      Hodgkin lymphoma also exceeded 5.0. Patients aged less than 65 years had higher
      SIRs than those who were older. In subsequent years, 6081 cancers were diagnosed
      (1.3, 1.3-1.3). Even 10 years or more after admission to hospital with VTE,
      cancer incidence had increased (1.3, 1.3-1.4). INTERPRETATION: At the time of VTE
      or in the first year afterwards, we found a large increase in the risk for
      diagnosis of virtually all cancers. In subsequent years, a persistent 30%
      increase in risk remains. Either premalignant change promotes thrombosis, or
      cancer and thrombosis share common risk factors.

PMID- 9660576
TI  - Case-control study of risk factors of Creutzfeldt-Jakob disease in Europe during
      1993-95. European Union (EU) Collaborative Study Group of Creutzfeldt-Jakob
      disease (CJD).
AB  - BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a transmissible spongiform
      encephalopathy. Genetic and iatrogenic forms have been recognised but most are
      sporadic and of unknown cause. We have studied risk factors for CJD as part of
      the 1993-95 European Union collaborative studies of CJD in Europe. METHODS: The
      405 patients with definite or probable CJD who took part in our study had taken
      part in population-based studies done between 1993 and 1995 in Belgium, France,
      Germany, Italy, the Netherlands, and the UK. Data on putative risk factors from
      these patients were compared with data from 405 controls. FINDINGS: We found
      evidence for familial aggregation of CJD with dementia due to causes other than
      CJD (relative risk [RR] 2.26, 95% CI 1.31-3.90). No significant increased risk of
      CJD in relation to a history of surgery and blood transfusion was shown. There
      was no evidence for an association between the risk of CJD and the consumption of
      beef, veal, lamb, cheese, or milk. No association was found with occupational
      exposure to animals or leather. The few positive findings of the study include
      increased risk in relation to consumption of raw meat (RR 1.63 [95% CI 1.18
      2.23]) and brain (1.68 [1.18-2.39]), frequent exposure to leather products (1.94
      [1.13-3.33]), and exposure to fertiliser consisting of hoofs and horns (2.32
      [1.38-2.91]). Additional analyses, for example stratification by country and of
      exposures pre-1985 and post-1985, suggest that these results should be
      interpreted with great caution. INTERPRETATION: Within the limits of the
      retrospective design of the study, our findings suggest that genetic factors
      other than the known CJD mutations may play an important part in CJD. Iatrogenic
      transmission of disease seems rare in this large population-based sample of
      patients with CJD. There is little evidence for an association between the risk
      of CJD and either animal exposure, or consumption of processed bovine meat or
      milk products for the period studied.

PMID- 9660577
TI  - Postnatal growth and health in children born after cryopreservation as embryos.
AB  - BACKGROUND: There is uncertainty about the health of children born from in-vitro
      fertilisation (IVF) with cryopreserved embryos. We investigated the postnatal
      growth and health (up to 18 months) of these children compared with those born
      after standard IVF with fresh embryos and those from spontaneous pregnancies.
      METHODS: 255 children from cryopreserved embryos were matched by maternal age,
      parity, single or twin pregnancy, and date of delivery with 255 children born
      after IVF with fresh embryos, and 252 children from spontaneous pregnancies. The
      main endpoint was growth; secondary endpoints were the prevalence of chronic
      illness, major malformations, cumulative incidence of common diseases, and
      development during the first 18 months. Growth was assessed by comparison with
      standard Swedish growth charts and by standard deviation scores. FINDINGS: Growth
      features were similar for both singletons and twins in the three groups. There
      were 6 (2.4%) of 255, 9 (3.5%) of 255, and 8 (3.2%) of 252 major malformations in
      the cryopreserved group, standard IVF, and spontaneous groups, respectively
      (p=0.6 between the cryopreserved and standard IVF group). The prevalence of
      chronic diseases did not differ between the three groups, with 18.0%, 15.3%, and
      16.7% of children with a chronic illness in the cryopreserved group, standard
      IVF, and spontaneous groups, respectively. INTERPRETATION: The cryopreservation
      process does not adversely affect the growth and health of children during
      infancy and early childhood. Minor handicaps, behavioural disturbances, learning
      difficulties, and dysfunction of attention and perception cannot be ruled out at
      this age.

PMID- 9660578
TI  - Randomised investigation of effects of pentoxifylline on left-ventricular
      performance in idiopathic dilated cardiomyopathy.
AB  - BACKGROUND: There is accumulating evidence that inflammatory cytokines have an
      important role in the pathogenesis of heart failure. Plasma concentrations of
      tumour necrosis factor alpha (TNF-alpha) are high in heart failure and have been
      correlated with the severity of symptoms. Pentoxifylline suppresses the
      production of TNF-alpha. This study aimed to assess the effects of pentoxifylline
      on left-ventricular function and functional class in patients with idiopathic
      dilated cardiomyopathy. METHODS: We undertook a single-centre, prospective,
      double-blind, randomised, placebo-controlled trial, in which 28 patients with
      idiopathic dilated cardiomyopathy were assigned pentoxifylline 400 mg three times
      daily or matching placebo. Clinical, echocardiographic, and radionuclide
      assessments were done at baseline and after 6 months of treatment. Primary
      endpoints were New York Heart Association (NYHA) functional class and left
      ventricular function. FINDINGS: Baseline characteristics were similar in the two
      groups. Four patients died during the study period, all in the placebo group.
      After 6 months of treatment, the proportion of patients in NYHA functional class
      I or II was higher in the pentoxifylline group than in the placebo group (14/14
      vs 10/14; p=0.01), and ejection fraction was higher in the pentoxifylline group
      than in the placebo group (mean 38.7% [SD 15.0] vs 26.8% [11.0], p=0.04). At 6
      months, TNF-alpha plasma concentrations were significantly lower in the
      pentoxifylline-treated group than in the placebo group (2.1 [1.0] vs 6.5 [5.0]
      pg/mL, p=0.001). INTERPRETATION: Our results suggest that pentoxifylline improves
      symptoms and left-ventricular systolic function in patients with idiopathic
      dilated cardiomyopathy. These results must be confirmed in larger-scale trials.

PMID- 9660579
TI  - Poliomyelitis-like illness due to Japanese encephalitis virus.
AB  - BACKGROUND: Acute flaccid paralysis remains common among Vietnamese children
      despite a pronounced fall in the incidence of poliomyelitis. METHODS: During
      1995, all 22 children presenting with acute flaccid paralysis to a referral
      centre in Ho Chi Minh City, Vietnam, had virological cultures and antibody
      measurements done on serum, cerebrospinal fluid, and faeces. A year later the
      children were reassessed and electrophysiological studies were done. FINDINGS:
      Wild poliovirus type 1 was isolated from the faeces of only one patient, and non
      polio enteroviruses from three patients. 12 (55%) of the 22 children with acute
      flaccid paralysis had evidence of acute Japanese encephalitis virus (JEV)
      infection, compared with only one (1%) of 88 age-matched hospital controls
      (children with diphtheria; p<0.0001). Compared with JEV-negative patients,
      weakness in JEV-infected children was more rapid in onset, tended to be
      asymmetrical, but was less likely to involve the arms. All 12 children with JEV
      infection were febrile at the onset of weakness, seven had acute retention of
      urine, and ten had CSF pleiocytosis. Seven of eight JEV-negative patients met the
      case-definition of Guillain-Barre syndrome, compared with only one of 12 JEV
      positive children. At follow-up, patients with JEV infection had greater
      disability and were more likely to have muscle wasting than were JEV-negative
      children. Nerve conduction and electromyographic studies indicated damage to the
      anterior horn cells. INTERPRETATION: JEV causes an acute flaccid paralysis in
      children that has similar clinical and pathological features to poliomyelitis. In
      endemic areas, children with acute flaccid paralysis should be investigated for
      evidence of JEV infection.

PMID- 9660580
TI  - An Asian man with enlarged glands.

PMID- 9660581
TI  - Intake of trans fatty acids in western Europe: the TRANSFAIR study.

PMID- 9660582
TI  - Airway obstruction caused by rheumatoid cricoarytenoid arthritis.

PMID- 9660583
TI  - Climate variability and transmission of epidemic polyarthritis.

PMID- 9660584
TI  - Ageusia as an adverse effect of phenytoin treatment.

PMID- 9660585
TI  - The confounding influence of sun exposure in melanoma.

PMID- 9660586
TI  - Arthritis, uveitis, and Stevens-Johnson syndrome induced by trimethoprim.

PMID- 9660587
TI  - Antimony and sudden infant death syndrome.

PMID- 9660588
TI  - Tubby-like protein-1 mutations in autosomal recessive retinitis pigmentosa.

PMID- 9660589
TI  - Is there evidence for vector transmission of GBV-C?

PMID- 9660591
TI  - Cerebrospinal-fluid tau protein and aspartate aminotransferase in Parkinson's
      disease.

PMID- 9660590
TI  - Folate deficiency, neural tube defects, and cardiac disease in UK Indians and
      Pakistanis.

PMID- 9660592
TI  - Motion sickness, migraine, and menstruation in mariners.

PMID- 9660593
TI  - Experts argue about tamoxifen prevention trial.

PMID- 9660594
TI  - Molecular biologists map pathways to gastrointestinal cancer.

PMID- 9660595
TI  - Waxing hot and cold in the surgical arena.

PMID- 9660596
TI  - UK government announces first "health action zones".

PMID- 9660597
TI  - Ectopic pregnancy.

PMID- 9660598
TI  - Analysis of a survey of 36 French research committees on intracytoplasmic sperm
      injection.
AB  - BACKGROUND: In France, when a new medical technology is to be applied
      experimentally to human beings, it must adhere to the principles stipulated by
      the Huriet-Serusclat law on biomedical research. This law requires that the
      validation of a protocol applicable to human beings, with its corollary
      protection and information dimensions, is first submitted to a research
      committee, known as a Consultative Committee Protecting Persons in Biomedical
      Research (CCPPRB). We aimed to survey the competence of these committees in
      biotechnology, and whether or not intracytoplasmic sperm injection (ICSI) had
      been considered by the committees as being an innovative treatment. METHODS: We
      presented each of France's 48 CCPPRBs with a questionnaire to assess the choices
      and criteria for making decisions that arose at the time ICSI was implemented in
      the different centres in each region. FINDINGS: 36 committees took part. We found
      that ICSI had been largely introduced in settings outside the scope of the
      CCPPRBs and of the framework fixed by the law on biomedical research. Only three
      centres for medically assisted reproduction had submitted applications to a
      CCPPRB, although ICSI has been implemented in over 20 centres. 21 (58%)
      committees were of the opinion that the implementation of ICSI could have come
      under their supervision. 24 (67%) committees believed that, independently of
      their own involvement, evaluation procedures for ICSI should have been specified
      before centres decided to introduce it. INTERPRETATION: We observed important
      differences in the way CCPPRBs handled ICSI as being within or outside the
      medical research field. The status of the research committees is legally and
      identically defined. However, committees did not agree on the definition of the
      limits of their action, and, therefore, their handling of the same issue
      differed. An inquiry is needed to define how, now that ICSI is done in many
      centres, it should adhere to principles of evaluation and safety already in
      existence for other medical technologies.

PMID- 9660599
TI  - Mrs Woolf in Harley Street.

PMID- 9660600
TI  - Israel's ban on use of Ethiopians' blood: how many infectious donations were
      prevented?

PMID- 9660601
TI  - The cervical screening muddle.

PMID- 9660602
TI  - The cervical screening muddle.

PMID- 9660603
TI  - The cervical screening muddle.

PMID- 9660604
TI  - The cervical screening muddle.

PMID- 9660605
TI  - The cervical screening muddle.

PMID- 9660606
TI  - Connexin-26 mutations and inherited deafness.

PMID- 9660607
TI  - Molecular genetic tests in surgical management of familial adenomatous polyposis.

PMID- 9660608
TI  - Hippocampal damage caused by seizures in temporal lobe epilepsy.

PMID- 9660609
TI  - Nevirapine and rashes.

PMID- 9660610
TI  - Pyoderma gangrenosum.

PMID- 9660611
TI  - Pyoderma gangrenosum.

PMID- 9660612
TI  - Colchicine in pyoderma gangrenosum.

PMID- 9660613
TI  - Circulating ICAM-1 in peripheral arterial disease as a predictor of adverse
      events.

PMID- 9660614
TI  - Compensatory hyperhidrosis after thoracic sympathectomy.

PMID- 9660615
TI  - Compensatory hyperhidrosis after thoracic sympathectomy.

PMID- 9660616
TI  - Visceral leishmaniasis in Liguria, Italy.

PMID- 9660617
TI  - Our healthier nation, possibly.

PMID- 9660618
TI  - Our healthier nation, possibly.

PMID- 9660619
TI  - Our healthier nation, possibly.

PMID- 9660620
TI  - The art and science of nursing.

PMID- 9660621
TI  - The art and science of nursing.

PMID- 9660622
TI  - Spinning more yarn: endozepine.

PMID- 9660623
TI  - Stumbling in science studies.

PMID- 9660624
TI  - [Basal meningitis].

PMID- 9660625
TI  - International Workshop on Bone Research in Space. Tokyo, Japan, November 11-13,
      1996. Proceedings.

PMID- 9660626
TI  - Proceeding of the Anaesthetic Research Society. St Bartholomew's Hospital,
      London. November 20-22, 1997.

PMID- 9660627
TI  - In memoriam Paul Boulanger (21 November 1905-16 June 1996).

PMID- 9660628
TI  - Joint meeting of the Benelux Society for Microcirculation and the Gesellschaft
      fur Mikrozirkulation e.V. Mainz, Germany, October 23-25, 1997. Abstracts.

PMID- 9660629
TI  - Recent developments in computer-assisted analysis of mixtures.
AB  - This paper reviews recent developments in the area of computer-assisted analysis
      of mixture distributions (C.A.MAN). Given a biometric situation of interest in
      which, under homogeneity assumptions, a certain parametric density occurs, such
      as the Poisson, the binomial, the geometric, the normal, and so forth, then it is
      argued that this situation can easily be enlarged to allow a variation of the
      scalar parameter in the population. This situation is called unobserved
      heterogeneity. This naturally leads to a specific form of nonparametric mixture
      distribution that can then be assumed to be the standard model in the biometric
      application of interest (since it also incorporates the homogeneous situations as
      a special case). Besides developments in theory and algorithms, the work focuses
      on developments in biometric applications such as meta-analysis, fertility
      studies, estimation of prevalence under clustering, and estimation of the
      distribution function of survival time under interval censoring. The approach is
      nonparametric for the mixing distribution, including leaving the number of
      components (subpopulations) of the mixing distribution unknown.

PMID- 9660631
TI  - An additive frailty model for correlated life times.
AB  - A frailty model for multivariate correlated life times is considered. The model
      both extends, in a rather straight-forward way, ordinary survival analysis with
      its emphasis on hazard modeling and incorporates well-known variance components
      models to account for the dependence between events of related individuals.
      Different approaches to estimation and inference are considered. An example from
      an ongoing study of genetic and environmental influences on premature death in
      adults serves to motivate and illustrate the model. Multivariate frailty models
      offer a conceptually simple and promising framework for analysis of correlated
      event times data, even if current knowledge is too sparse for such models to be
      tested critically.

PMID- 9660630
TI  - On the analysis of mixed longitudinal growth data.
AB  - Mixed longitudinal growth data consists of several observations on a
      characteristic over a limited age range for each individual in a study. This data
      is then combined to model growth over the total age range of all individuals in
      the study. The limited data collected on each individual precludes a subject
      specific approach to modelling so that a population-based approach must be used.
      Here we propose a method for the analysis of mixed longitudinal data using linear
      models constructed from cubic splines to model both the mean and variance curves
      of an observed characteristic. The method is illustrated on growth in height and
      head circumference for children in a recently collected mixed longitudinal data
      set concerning the growth of Victorian schoolchildren, where particular concern
      was the timing of growth spurts and increases in variability.

PMID- 9660632
TI  - A nonparametric approach to a survival study with surrogate endpoints.
AB  - A nonparametric estimator for the joint distribution of a survival time and
      surrogate response time, which may occur earlier during follow-up, is presented.
      In the absence of the surrogate response variable, the estimator reduces to the
      Kaplan Meier nonparametric estimator for the survival time alone. The estimator
      derived in this paper is done so in a particular novel way using an exchangeable
      process (reinforced random walks) to model individual observations. The
      methodology introduced in the paper is readily extended to modelling multiple
      state processes.

PMID- 9660633
TI  - Stratified testing for treatment effects with missing data.
AB  - Dawson and Lagakos (1993, Biometrics 49,1022-1032) proposed a stratified test for
      repeated measures data that contain missing observations. They recommended
      stratification based on missing data patterns and considered sufficient
      conditions under which the size of the test is properly retained. In this paper,
      we point out some practical problems with these conditions and illustrate them
      with their CD4 count example as well as a stimulation study. We give a less
      stringent condition and delineate its merit. We also discuss what to do when none
      of the conditions are met.

PMID- 9660634
TI  - Difference or ratio? A note on two-treatment, four-sequence analysis.

PMID- 9660635
TI  - Rapid review.

PMID- 9660636
TI  - Save time with diabetes education.

PMID- 9660637
TI  - Proposal for a section of family medicine maternity care in the College of Family
      Physicians of Canada.

PMID- 9660638
TI  - Retraction.

PMID- 9660639
TI  - Too much O2?

PMID- 9660640
TI  - Antibacterial action of dipeptides containing an inhibitor of glucosamine-6
      phosphate isomerase.
AB  - Several dipeptides, containing the N3-(4-methoxyfumaroyl)-L-2,3-diaminopropanoic
      acid (FMDP) moiety linked to protein and non-protein amino acids, exhibited a
      strong growth-inhibitory and bactericidal effect against Bacillus subtilis. FMDP
      dipeptides were efficiently transported into bacterial cells by a di-tripeptide
      permease and subsequently cleaved by intracellular Mn2+/Co2+-dependent
      peptidases. Cleavage rates [0.1-5.6 micromol min-1 (mg protein)-1] were about two
      orders of magnitude lower than transport rates [40-200 micromol min-1 (mg dry wt)
      1]. The released FMDP inactivated glucosamine-6-phosphate (GlcN-6-P) isomerase,
      an enzyme catalysing the first committed step in a biosynthetic pathway leading
      to amino sugar-nucleotide precursors of bacterial peptidoglycan. Inhibition of
      GlcN-6-P isomerase precluded peptidoglycan biosynthesis and resulted in a strong
      bacteriolytic effect. Results of the studies on consequences of GlcN-6-P
      isomerase inhibition upon the action of FMDP-dipeptides provided evidence
      demonstrating that the lack of endogenous GlcN-6-P could be a reason for the
      triggering of bacterial autolysis. Peptides containing the inhibitors of GlcN-6-P
      isomerase are one of the very few antimicrobial agents known that exhibit both
      bactericidal and fungicidal effects.

PMID- 9660641
TI  - [3rd Congress of the French Society of Blood Transfusion. Marseille, France, 28
      30 April 1998].

PMID- 9660642
TI  - Choosing an accident and emergency department computer system.

PMID- 9660644
TI  - Central and East European Regional INTERASMA Conference. Budapest, Hungary,
      August 24-27, 1997.

PMID- 9660643
TI  - Direct arteriovenous fistulas (carotid-cavernous and vertebral-venous). Diagnosis
      and intervention.
AB  - Carotid-cavernous and vertebral-venous fistulas are direct arteriovenous
      fistulas. Their symptoms range from benign to extremely severe ophthalmologic or
      neurologic complications. Mechanism of symptoms is mostly related to venous
      drainage. Therapy is widely indicated, as today's endovascular techniques--using
      mostly detachable balloons and coils--have a high success rate and very few
      complications.

PMID- 9660645
TI  - Summary of symposium, antisense oligonucleotides: strategies and successes.
      Sarasota, Florida, USA. April 21, 1995.

PMID- 9660646
TI  - International forensic science and justice.

PMID- 9660647
TI  - Proceedings of the 6th Congress of the Societe de Pharmaco-Toxicologie Cellulaire
      and the Societe Francaise de Toxicologie Genetique. Paris, France, March 6-7,
      1997.

PMID- 9660649
TI  - Bibliography on syringe-exchange references.

PMID- 9660648
TI  - The Italian Association for the Study of Glaucoma. Proceedings of the 12th annual
      general meeting. Rapallo, Italy, 14-15 March 1997.

PMID- 9660650
TI  - Task Force on Dental Education submits final report.

PMID- 9660651
TI  - Sudden cryptococcal deafness.

PMID- 9660652
TI  - Aging andlongevity: towards the next millennium. The Bat Sheva Le Rothschild
      International Seminar on Cellular, Molecular and Genetic Aspects of Aging and
      Longevity. Zichron Yaacov, Israel, 7-12 December 1997.

PMID- 9660653
TI  - Molecular medicine through the kaleidoscope. The 30th Miami Winter Symposium:
      Molecular Biology in the Conquest of Disease. Miami, Fl, USA, 7-11 February 1998.

PMID- 9660654
TI  - Regional Development 1996. South American starter cultures.

PMID- 9660655
TI  - Regional Development 1996. Quebec biotechnology: the quiet revolution.

PMID- 9660656
TI  - Regional Development 1996. Partnering in Japan.

PMID- 9660657
TI  - Regional Development 1996. Biotechnology in Southeast Asia.

PMID- 9660658
TI  - Regional Development 1996. The Caledonian way.

PMID- 9660659
TI  - Regional Development 1996. Switzerland: at a turning point.

PMID- 9660660
TI  - Regional Development 1996. Wisconsin-grown biotechnology.

PMID- 9660661
TI  - Regional Development 1996. An international listing of regional development
      organizations.

PMID- 9660662
TI  - Report of the 61st National Scientific Meeting of the American College of
      Rheumatology, Washington DC, 8-12 November 1997.

PMID- 9660663
TI  - [Artashes Ivanovich Karamian (to the 90th birthday)].

PMID- 9660664
TI  - [Topical dictionary].

PMID- 9660665
TI  - The Salernitan school.

PMID- 9660667
TI  - USAN Council. List No. 404. New names. Nagrestipen.

PMID- 9660666
TI  - The hepatopulmonary syndrome.
AB  - Impaired arterial oxygenation, ranging from an increased alveolar-arterial oxygen
      gradient to severe hypoxaemia, is commonly reported in patients with advanced
      liver disease. Hepatopulmonary syndrome is defined by the clinical triad of liver
      disease, alveolar-arterial oxygen gradient of >15 mmHg, evidence of
      intrapulmonary vascular dilatations. Three methods are available for detecting
      intrapulmonary vascular dilatations: contrast-enhanced echocardiography,
      technetium 99m-labelled macroaggregated albumin scanning and pulmonary
      arteriography. A recent hypothesis that assigns to nitric oxide the crucial role
      as mediator of abnormal pulmonary vasodilatation and oxygen is discussed; the
      measurement of nitric oxide in the exhaled air may represent a possible marker of
      gas exchange abnormalities in liver disease. The therapeutic options to relieve
      the hepatopulmonary syndrome are discussed. While no pharmacological treatment
      has proved to be clinically useful, liver transplantation was reported to cure
      the response to transplantation is discussed. The response of hypoxaemia to 100%
      oxygen breathing appears to be the most important prognostic factor of
      perioperative death rate.

PMID- 9660668
TI  - [Remarks regarding the paper by T. Blaszczyk and S. Pielka: "Analysis of hand
      injuries sustained at work treated on an outpatient basis"].

PMID- 9660669
TI  - [Management of polytrauma. Preclinical handling and shock unit management].

PMID- 9660670
TI  - [Influences on medical performance capacity or lowering the medical standard].

PMID- 9660672
TI  - Clustered mutations have no effect on the overdispersed molecular clock: a
      response to Huai and Woodruff.

PMID- 9660671
TI  - Proposed genetic nomenclature rules for Tetrahymena thermophila, Paramecium
      primaurelia and Paramecium tetraurelia. The Seventh International Meeting on
      Ciliate Molecular Biology Genetics Nomenclature.

PMID- 9660673
TI  - Clusters of identical new mutations can not account for the "overdispersed"
      molecular clock.

PMID- 9660674
TI  - With the correct concept of mutation rate, cluster mutations can explain the
      overdispersed molecular clock.

PMID- 9660675
TI  - Salmon--parasitology and beyond.

PMID- 9660676
TI  - Results in parenchymal strips vs. the intact inflated lung.

PMID- 9660677
TI  - Endotoxemia affects lung vascular prostanoid metabolism in rabbits.

PMID- 9660678
TI  - How trends in managed care affect family physicians.

PMID- 9660679
TI  - [Case presentation: Unmasking central serous chorioretinopathy].

PMID- 9660680
TI  - Retraction: Is Kaposi's sarcoma-associated herpesvirus in semen of HIV-infected
      homosexual men?

PMID- 9660681
TI  - Vena caval filters for the prevention of pulmonary embolism.

PMID- 9660682
TI  - Vena caval filters for the prevention of pulmonary embolism.

PMID- 9660683
TI  - Vena caval filters for the prevention of pulmonary embolism.

PMID- 9660684
TI  - Transplantation of kidneys from donors whose hearts have stopped.

PMID- 9660685
TI  - Analgesic nephropathy.

PMID- 9660686
TI  - Analgesic nephropathy.

PMID- 9660687
TI  - Analgesic nephropathy.

PMID- 9660688
TI  - Analgesic nephropathy.

PMID- 9660689
TI  - Health insurance and access to primary care for children.

PMID- 9660690
TI  - Health insurance and access to primary care for children.

PMID- 9660691
TI  - Health insurance and access to primary care for children.

PMID- 9660692
TI  - Who will pay for graduate medical education?

PMID- 9660693
TI  - Who will pay for graduate medical education?

PMID- 9660694
TI  - Treatment of antibiotic-resistant Helicobacter pylori.

PMID- 9660695
TI  - [Development, effects and overcoming resignation-related "low EE behavior" in an
      inpatient team toward a patient with chronic schizoaffective psychosis].

PMID- 9660696
TI  - [Shame-based mania].

PMID- 9660697
TI  - [Acoustic hallucinosis in an elderly patient--induced by diltiazem
      hydrochloride].

PMID- 9660698
TI  - [Joint annual session of the North German Society of Radiology and the Radiology
      Society of Lower Saxony and Sachsen Anhalt. Kiel, 20-21 February 1998.
      Abstracts].

PMID- 9660699
TI  - Fighting germs.

PMID- 9660700
TI  - How anthrax kills.

PMID- 9660701
TI  - Early Americans.

PMID- 9660702
TI  - Areas of the brain: movements and memories.

PMID- 9660703
TI  - Voters reject antigenetics initiative.

PMID- 9660704
TI  - Editors call for misconduct watchdog.

PMID- 9660705
TI  - Biomedical patents. Making research tools more accessible.

PMID- 9660706
TI  - Research ethics. NIH examines standards for consent.

PMID- 9660707
TI  - Sifting through and making sense of genome sequences.

PMID- 9660708
TI  - First AIDS vaccine trial launched.

PMID- 9660709
TI  - A molecular biology network for Asia and the Pacific Rim.

PMID- 9660710
TI  - The biology of being frazzled.

PMID- 9660711
TI  - Cytochrome c oxidase: one enzyme, two mechanisms?

PMID- 9660712
TI  - Hominid brain evolution: looks can be deceiving.

PMID- 9660713
TI  - [Statistical report on health care in the Czech Republic in 1996].

PMID- 9660714
TI  - Neurone development and death, from a cell biologist's perspective.

PMID- 9660715
TI  - [3rd Neurotrauma/Polytrauma Symposium. Cologne, Germany, March 14-15, 1998.
      Abstracts].

PMID- 9660716
TI  - Neuroimmunomodulation: Molecular Aspects, Integrative Systems, and Clinical
      Advances. Proceedings of the 3rd Congress of the International Society of
      NeuroImmunoModulation (ISNIM). Bethesda, Maryland, USA. November 13-15 , 1996.

PMID- 9660717
TI  - Fourth International Symposium on the Immunotherapy of the Rheumatic Diseases. 21
      25 May 1997, Cyprus.

PMID- 9660718
TI  - Morphological evidence for the location of calcitonin gene-related peptide (CGRP)
      immunoreactivity in rat lymphocytes.
AB  - Calcitonin gene-related peptide (CGRP) is widely distributed in sensory neurons
      and nerve fibers. It was shown recently in our laboratory that there was CGRP
      immunoreactivity (CGRP-ir) in extract of rat lymphocyte of thymus and mesenteric
      lymph node by radioimmunoassay and reversed-phase HPLC. The aim of this study was
      to detect the CGRP-ir location in the rat lymphocyte by immunocytochemical
      method. Single cells isolated from thymus and mesenteric lymph node of male
      Wistar rat (200-250 g) were suspended in RPMI-1640 medium. After adhesion to
      plate wall and through nylon wool fiber columns, T cell-riched suspension was
      obtained. Immunocytochemical ABC method was performed in cell suspension, the
      specific antiserum (1:200 diluted) was rabbit anti-human CGRP. The cells were
      examined under light microscope after smeared on glass slide by Shandon Cytospin.
      The results showed that some lymphocytes were CGRP-ir positive. The positive
      granules were seen as ring, plaque, cap or spot distributing on the surface or
      inside the cell. The results indicate that CGRP-ir may be located in some rat T
      lymphocytes. This work provides new information about the interaction between the
      nervous and the immune systems. The functional significance of CGRP located in
      lymphocytes needs to be further studied.

PMID- 9660719
TI  - RT in situ PCR for the detection of mRNA transcripts of Fas-L in the immune
      privileged placental environment.
AB  - Rapid and reproducible detection of RNA in cells and tissue sections is routinely
      accomplished using in-situ hybridization technique provided that the target
      number of mRNA copies is above a minimum number. Detection of low copy
      transcripts is problematic when threshold detection occurs below clear signal
      resolution or alternatively, when technical problems result in background noise
      which occludes clear signal. RT in-situ PCR methodology utilizes both the power
      and specificity of PCR to amplify target whose localization is subsequently
      detected at the cellular level. RT in-situ PCR methods routinely involve a two
      step methodology. mRNA copies are initially transcribed into cDNA. This step is
      followed by a separate PCR step wherein amplification of the newly synthesized
      cDNA takes place. A simplified one-step procedure biochemically compartmentalizes
      these sequential steps within a single applications methodology using the enzyme
      rTth. This method was successfully applied to detect and localize mRNA
      transcripts for Fas ligand within the immune privileged placental environment and
      to provide verification of immunohistochemical localization of gene product.

PMID- 9660720
TI  - Specific primer design and exonuclease III treatment for the reduction of
      nonspecific staining in direct in situ PCR.
AB  - Although direct in situ PCR is more rapid than indirect method for the in situ
      identification of low copy number genes, several reports indicate serious
      nonspecific signals with this method. Some procedures have been reported in an
      effort to eliminate the nonspecific signals, but the results have not been
      satisfactory. Exonuclease III can progressively digest blunt or recessed 3'
      termini of double-stranded DNA whereas DNA with 3' overhanging end is resistant
      to digestion. DNA fragments amplified by PCR with primers incorporating the
      recognition site for Sph I generate 3' four bases extensions at both end after
      digestion. These fragments are expected to be resistant to exonuclease III
      digestion. It is also expected that nonspecifically incorporated digoxigenin
      would be released by treatment with exonuclease III thereby reducing background.
      We succeeded in digesting selectively with the samples after standard PCR by Sph
      I and exonuclease III treatment. However, we failed to eliminate the nonspecific
      signals of direct in situ PCR. Southern blotting revealed that the amount of
      nonspecific incorporation was so huge that exonuclease III was unable to release
      all of nonspecifically incorporated digoxigenin and maintain specific
      incorporated digoxigenin simultaneously. Direct in situ PCR is a sensitive
      method. However, its specificity has a significant problem.

PMID- 9660721
TI  - Evaluation of membranous staining of mesothelioma.
AB  - Panels of immunohistochemical markers are often used to aid in categorizing
      malignant neoplasms involving the pleura. While epithelial membrane antigen (EMA)
      and human milk fat globule-2 (HMFG-2) are each reported to stain the majority of
      cases of adenocarcinoma and mesothelioma, authors have reported that the pattern
      of staining for these two antibodies can be a useful discriminant. Both are
      described as revealing a membranous pattern of staining for mesothelioma and a
      cytoplasmic staining pattern in adenocarcinoma. Immunostains were performed on 23
      cases of malignant mesothelioma and 22 cases of adenocarcinoma. For EMA, 78% of
      mesotheliomas and 86% of adenocarcinomas stained positively, and 65% of
      mesotheliomas vs. 14% of adenocarcinomas exhibited a membranous staining pattern.
      For HMFG-2, 9% of mesotheliomas and 50% of adenocarcinomas stained positively,
      and 4% of mesotheliomas vs. 9% of adenocarcinomas exhibited a membranous staining
      pattern. Membranous staining for HMFG-2 was not a useful criterion. In this
      series, a membranous pattern of staining for EMA had a sensitivity of 65% and a
      specificity of 86% for the identification of malignant mesothelioma.

PMID- 9660722
TI  - Ultrastructural observations on the cells of a patient with Fanconi's anemia
      transforming to acute leukemia.
AB  - The ultrastructural findings in the bone marrow and peripheral blood cells of a
      patient with Fanconi's anemia transforming to acute myelo-monocytic leukemia are
      presented. They consisted of an unusual large number of nuclear pockets, bridges
      and appendices observed in the nuclei of the polymorphonuclear cells, monocytes
      and to a lesser extent in the mature normoblasts. Since the mother and two
      younger brothers of the propositus were found to have macrocytic anemia and
      pancytopenia, most probably Fanconi's anemia, their peripheral blood cells were
      also examined with the electron microscope. The cells of all of them showed
      similar nuclear alterations, although in lesser quantity. The possibility that
      these findings are consistent with the diagnosis of Fanconi's anemia, or they
      herald an evolution of the disease to acute leukemia is considered.

PMID- 9660723
TI  - Technical considerations in immunocytochemistry.

PMID- 9660724
TI  - Introduction to the genetics of cancer.

PMID- 9660725
TI  - Applications of tissue microdissection in cancer genetics.
AB  - A major obstacle to apply molecular biologic techniques effectively to the
      somatic genetic analysis of neoplastic tissue is the presence of abundant
      nonneoplastic elements in the analyzed specimen. These nonneoplastic elements,
      including reactive fibrous cells, vascular cells, and a variety of infiltrating
      white blood cells, may mask genetic alterations that otherwise would be easily
      detectable if the neoplastic cells were procured selectively. We have developed a
      microdissection technique which allows to selectively procure and genetically
      analyze small populations of neoplastic cells from the glass slide. In this
      report, we describe the microdissection technique and genetic analysis of
      archival frozen and paraffin-embedded tissue in general. Then, we review some
      implications of this approach of genetic analysis for mapping and cloning of new
      genes, identification of premalignant lesions, and differential analysis of
      different histologic components within the same tumor.

PMID- 9660726
TI  - FISH: recent advances and diagnostic aspects.
AB  - In situ Hybridization (ISH), since its introduction in 1969 by Gall and Pardue
      has found multiple uses in molecular morphology due to its unique capability of
      visualizing nucleic acid sequences without altering the cell's cytological,
      chromosomal or histological integrity. Fluorescence in situ Hybridization (FISH)
      has established itself as a variation of the traditional hybridization process
      whereby the probes utilized are a fluorescently labeled and produce bright clear
      signals upon detection. FISH is involved in localizing and exploring chromosomal,
      genetic and genomic aberrations that are often directly correlated to disease
      causation and progression. This technique is used as an essential tool not only
      in research laboratories, but also in prognostics, diagnostics and disease
      monitoring in medicine. In the past decade, there have appeared multiple
      modifications to traditional FISH technology allowing a wider variety of
      practical applications. Some of the latest innovative techniques discussed in
      this review paper are Forward and Reverse Chromosome Painting, Chromosome in situ
      suppression hybridization (CISS), Multicolor FISH, Chromosomal bar coding, Micro
      FISH, In situ Hybridization to mRNA, in-cell RT-PCR, Fluorescence
      immunophonotyping and interphase cytogenetics as tool for investigation of
      neoplasmas (FICTION), Primed in situ DNA synthesis (PRINS), Fiber-FISH, FISHES,
      and Comparative genomic hybridization (CGH). This paper provides a brief overview
      of FISH and the techniques exploiting FISH modifications as well as their
      evaluation and discussion of practical applications.

PMID- 9660727
TI  - Molecular biology in transplantation medicine.
AB  - Serological methods of tissue typing have been used for matching patient-donor
      pairs for transplantation for several decades. Molecular techniques are rapidly
      being developed that can provide rapid, accurate tissue typing at the DNA
      sequence level. These techniques can be used to identify the best match pre
      transplant and can also be used for the post-transplant monitoring of engraftment
      of bone marrow transplant patients.

PMID- 9660728
TI  - Flow cytometry: an overview.
AB  - Flow cytometry is an innovative technology that measures certain cell parameters
      as the cells flow in a fluid stream and in single file past an analytical laser
      light source. Clinical applications of flow cytometry currently utilized in the
      laboratory include cell surface antigen determinations or immunophenotyping of
      hematologic cells, DNA analysis of hematopoietic malignancies and solid tumors,
      and measurement of CD4 (T helper/inducer cell) absolute counts and T helper/T
      suppressor (CD4/CD8) ratios in the evaluation of immune deficiency. Flow
      cytometry often offers a more rapid, sensitive, accurate, and quantitative means
      of analyzing a particular cell population in a heterogeneous cell suspension as
      compared to more traditional microscopic methods. This article is intended to
      provide a general understanding of the technological basis of how a flow
      cytometer functions as well as an overview of both current and future flow
      cytometric clinical laboratory applications.

PMID- 9660729
TI  - Recent advances in telepathology.
AB  - Telepathology is to transform microscopic and gross images of pathological
      specimen into digital forms and transmit them electronically to remote sites for
      consultation and collaboration. Many benefits can be derived from telepathology.
      Although still at its initial developing stage, this technology is beginning to
      change the way pathological practice is conducted. With the rapid advancement of
      computer and telecommunication sciences, telepathology is increasingly becoming
      more feasible and practical for pathologists. This review gives a comprehensive
      account of the recent development in telepathology, discusses its functionality,
      applications, limitations and potential, and serves as an introduction to this
      rapidly evolving field.

PMID- 9660730
TI  - The expanding role of molecular biology in clinical chemistry.
AB  - Technical improvements in the application of molecular biology methods to
      detection and identification of specific nucleic acid sequences have resulted in
      more widespread incorporation of these techniques into clinical laboratory
      services. Gene amplification techniques have been refined and automated, making
      possible the rapid and economical detection of attomolar and smaller quantities
      of genetic material. Of particular benefit to clinical chemistry applications is
      the remarkable specificity of a DNA probe for its complementary sequence.
      Applications of molecular biology techniques in clinical chemistry include
      diagnosis of infectious, neoplastic, genetic, and hematological diseases. In
      addition, the use of oligonucleotides as molecular recognition probes may provide
      new analytical strategies for a wide range of diagnostic applications that
      currently rely on antibodies.

PMID- 9660731
TI  - Detection of mRNA in tissue sections by in situ RT-PCR.

PMID- 9660732
TI  - The economics of new trends in pathology.

PMID- 9660733
TI  - High grade malignant fibrous histiocytomas have bimodal cycling populations of
      factor XIIIa+ dendrophages and dedifferentiated mesenchymal cells possibly
      derived from CD34+ fibroblasts.

PMID- 9660734
TI  - Observations on the role of FXIIIa+ dendritic mammary stromal cells in
      myofibroblastic stromal remodeling and angiogenesis in mammary carcinoma.

PMID- 9660735
TI  - Detection of hepatitis C virus RNA in liver tissues by in situ hybridization.

PMID- 9660736
TI  - Highly sensitive DNA, RNA and antigen detection methods: streptavidin-Nanogold
      silver staining.

PMID- 9660737
TI  - Detection of telomerase activity in microdissected breast lesions.

PMID- 9660738
TI  - Optimization of fluorescence in situ hybridization (FISH) in cytological
      specimens.

PMID- 9660739
TI  - Comparison of HBV DNA amplification with PCR in patients with serological
      evidence of HBV infection--a report from India.

PMID- 9660740
TI  - Principles for Sustainable Governance of the Oceans
AB  - Pressures being exerted on the ocean ecosystems through overfishing, pollution,
      and environmental and climate change are increasing. Six core principles are
      proposed to guide governance and use of ocean resources and to promote
      sustainability. Examples of governance structures that embody these principles
      are given.

PMID- 9660741
TI  - Biogeochemical Controls and Feedbacks on Ocean Primary Production
AB  - Changes in oceanic primary production, linked to changes in the network of global
      biogeochemical cycles, have profoundly influenced the geochemistry of Earth for
      over 3 billion years. In the contemporary ocean, photosynthetic carbon fixation
      by marine phytoplankton leads to formation of approximately 45 gigatons of
      organic carbon per annum, of which 16 gigatons are exported to the ocean
      interior. Changes in the magnitude of total and export production can strongly
      influence atmospheric CO2 levels (and hence climate) on geological time scales,
      as well as set upper bounds for sustainable fisheries harvest. The two fluxes are
      critically dependent on geophysical processes that determine mixed-layer depth,
      nutrient fluxes to and within the ocean, and food-web structure. Because the
      average turnover time of phytoplankton carbon in the ocean is on the order of a
      week or less, total and export production are extremely sensitive to external
      forcing and consequently are seldom in steady state. Elucidating the
      biogeochemical controls and feedbacks on primary production is essential to
      understanding how oceanic biota responded to and affected natural climatic
      variability in the geological past, and will respond to anthropogenically
      influenced changes in coming decades. One of the most crucial feedbacks results
      from changes in radiative forcing on the hydrological cycle, which influences the
      aeolian iron flux and, in turn, affects nitrogen fixation and primary production
      in the oceans.

PMID- 9660742
TI  - Acquisition and utilization of transition metal ions by marine organisms.
AB  - Recent research has revealed that trace metals, particularly transition metals,
      play important roles in marine productivity. Most of the work has been on iron,
      which shows a nutrient-depleted profile in the upper ocean. Marine organisms have
      a variety of means for acquiring iron and other transition metal ions that differ
      from those of terrestrial organisms.

PMID- 9660743
TI  - Climate-Ocean Variability and Ecosystem Response in the Northeast Pacific
AB  - The role of climatic variation in regulating marine populations and communities
      is not well understood. To improve our knowledge, the sign, amplitude, and
      frequency of climatic and biotic variations should be compared as a necessary
      first step. It is shown that there have been large interannual and interdecadal
      sea-surface temperature changes off the West Coast of North America during the
      past 80 years. Interannual anomalies appear and disappear rather suddenly and
      synchronously along the entire coastline. The frequency of warm events has
      increased since 1977. Although extensive, serial, biological observations are
      often incomplete, it is clear that climate-ocean variations have disturbed and
      changed our coastal ecosystems.

PMID- 9660744
TI  - Nutrient Biogeochemistry of the Coastal Zone
AB  - The coastal seas are one of the most valuable and vulnerable of Earth's habitats.
      Significant inputs of nutrients to the coastal zone arrive via rivers,
      groundwater, and the atmosphere. Nutrient fluxes through these routes have been
      increased by human activity. In addition, the N:P:Si ratios of these inputs have
      been perturbed, and many coastal management practices exacerbate these
      perturbations. There is evidence of impacts arising from these changes (in
      phytoplankton numbers and relative species abundance, and deep-water oxygen
      declines) in areas of restricted water exchange. Elsewhere, the nutrient fluxes
      through the coastal zone appear to be still dominated by large inputs from the
      open ocean, and there is little evidence of anthropogenic perturbations.

PMID- 9660745
TI  - The Quantum Event of Oceanic Crustal Accretion: Impacts of Diking at Mid-Ocean
      Ridges
AB  - Seafloor diking-eruptive events represent the irreducible, quantum events of
      upper oceanic crustal accretion. They record events by which a large portion of
      the oceanic crust has formed through geological history. Since 1993, the U.S.
      Navy's real-time Sound Surveillance System has allowed location of ongoing
      acoustic signatures of dike emplacement and basalt eruptions at ridge crests in
      the northeast Pacific. These diking-eruptive events trigger a sequence of
      related, rapidly evolving physical, chemical, and biological processes. Magmatic
      volatiles released during these events may provide nutrients for communities of
      subseafloor microorganisms, some of which thrive in high-temperature anaerobic
      environments. Many of the organisms identified from these systems are Archaea. If
      microorganisms can thrive in the water-saturated pores and cracks within deep,
      volcanically active portions of our planet, other hydrothermally active planets
      may harbor similar life forms.

PMID- 9660746
TI  - G protein-coupled receptors. II. Mechanism of agonist activation.

PMID- 9660747
TI  - Lineage-specific signaling in melanocytes. C-kit stimulation recruits p300/CBP to
      microphthalmia.
AB  - During melanocyte development, the cytokine Steel factor activates its receptor c
      Kit, initiating a signal transduction cascade, which is vital for lineage
      determination via unknown downstream nuclear targets. c-Kit has recently been
      found to trigger mitogen-activated protein kinase-mediated phosphorylation of
      Microphthalmia (Mi), a lineage-restricted transcription factor, which, like Steel
      factor and c-Kit, is essential for melanocyte development. This cascade results
      in increased Mi-dependent transcriptional reporter activity. Here we examine the
      mechanism by which Mi is activated by this pathway. Phosphorylation does not
      significantly alter Mi's nuclear localization, DNA binding, or dimerization.
      However, the transcriptional coactivator p300/CBP selectively associates with
      mitogen-activated protein kinase-phosphorylated Mi, even under conditions in
      which non-MAPK phospho-Mi is more abundant. Moreover, p300/CBP coactivates Mi
      transcriptional activity in a manner dependent upon this phosphorylation. Mi thus
      joins CREB as a transcription factor whose signal-responsive phosphorylation
      regulates coactivator recruitment, in this case modulating lineage development in
      melanocytes.

PMID- 9660748
TI  - Novel recognition motif on fibroblast growth factor receptor mediates direct
      association and activation of SNT adapter proteins.
AB  - Fibroblast growth factors (FGFs) stimulate tyrosine phosphorylation of a membrane
      anchored adapter protein, FRS2/SNT-1, promoting its association with Shp-2
      tyrosine phosphatase and upstream activators of Ras. Using the yeast two-hybrid
      protein-protein interaction assay, we show that FRS2/SNT-1 and a newly isolated
      SNT-2 protein directly bind to FGF receptor-1 (FGFR-1). A juxtamembrane segment
      of FGFR-1 and the phosphotyrosine-binding domain of SNTs are both necessary and
      sufficient for interaction in yeast and in vitro, and FGFR-mediated SNT tyrosine
      phosphorylation in vivo requires these segments of receptor and SNT. Our findings
      establish SNTs as direct protein links between FGFR-1 and multiple downstream
      pathways. The SNT binding motif of FGFR-1 is distinct from previously described
      phosphotyrosine-binding domain recognition motifs, lacking both tyrosine and
      asparagine residues.

PMID- 9660749
TI  - A Rac1 effector site controlling mitogenesis through superoxide production.
AB  - The Rac GTP-binding protein controls signal transduction pathways that are
      critical for mitogenesis and oncogenesis (1,2). The biochemical nature of these
      signaling pathways is presently unknown. Here we report that a region in Rac1
      (residues 124-135), previously defined as the insert region (3), is essential for
      its mitogenic activity. Deletion of this region does not interfere with the
      ability of Rac1 to induce cytoskeletal changes or to activate the Jun kinase
      mitogen-activated protein kinase cascade but abrogates Rac1-induced stimulation
      of DNA synthesis and Rac1-mediated superoxide production in quiescent
      fibroblasts. Treatment of cells with agents that abolish superoxide generation
      inhibits specifically the mitogenic effect of Rac1. Our results identify an
      effector site in Rac1 that is necessary for mitogenic signaling and implicate
      superoxide generation as a candidate effector pathway of Rac1-dependent cell
      growth.

PMID- 9660750
TI  - Secretory vesicle budding from the trans-Golgi network is mediated by
      phosphatidic acid levels.
AB  - Phospholipid metabolism plays a central role in regulating vesicular traffic in
      the secretory pathway. In mammalian cells, activation of a Golgi-associated
      phospholipase D activity by ADP-ribosylation factor results in hydrolysis of
      phosphatidylcholine to phosphatidic acid (PA). This reaction has been proposed to
      stimulate nascent secretory vesicle budding from the trans-Golgi network. It is
      unclear whether PA itself or diacylglycerol (DAG), a metabolite implicated in
      yeast secretory vesicle formation, regulates budding. To distinguish between
      these possibilities we have used a permeabilized cell system supplemented with
      phospholipid-modifying enzymes that generate either DAG or PA. The data
      demonstrate that in mammalian cells accumulation of PA rather than DAG is a key
      step in regulating budding of secretory vesicles from the trans-Golgi network.

PMID- 9660751
TI  - Topoisomerase II-mediated DNA cleavage and religation in the absence of base
      pairing. Abasic lesions as a tool to dissect enzyme mechanism.
AB  - The interaction of topoisomerase II with its DNA cleavage site is critical to the
      physiological functions of the enzyme. Despite this importance, the specific
      enzyme-DNA interactions that drive topoisomerase II-mediated DNA cleavage and
      religation are poorly understood. Therefore, to dissect interactions between the
      enzyme and its cleavage site, abasic DNA lesions were incorporated into a
      bilaterally symmetrical and identical cleavage site. Results indicate that
      topoisomerase II has unique interactions with each position of the 4-base
      overhang generated by enzyme-mediated DNA cleavage. Lesions located 2 bases 3' to
      the point of scission stimulated cleavage the most, whereas those 3 bases from
      the point of scission stimulated cleavage the least. Moreover, an additive and in
      some cases synergistic cleavage enhancement was observed in oligonucleotides that
      contained multiple DNA lesions, with levels reaching >60-fold higher than the
      wild-type substrate. Finally, topoisomerase II efficiently cleaved and religated
      a DNA substrate in which apyrimidinic sites were simultaneously incorporated at
      every position on one strand of the 4-base overhang. Therefore, unlike classical
      DNA ligases in which base pairing is the driving force behind closure of the DNA
      break, it appears that for topoisomerase II, the enzyme is responsible for the
      spatial orientation of the DNA termini for ligation.

PMID- 9660752
TI  - An essential component of a novel bacterial protein export system with homologues
      in plastids and mitochondria.
AB  - Proteins are transported across the bacterial plasma membrane and the chloroplast
      thylakoid membrane by means of protein translocases that recognize N-terminal
      targeting signals in their cognate substrates. Transport of many of these
      proteins involves the well defined Sec apparatus that operates in both membranes.
      We describe here the identification of a novel component of a bacterial Sec
      independent translocase. The system probably functions in a similar manner to a
      Sec-independent translocase in the thylakoid membrane, and substrates for both
      systems bear a characteristic twin-arginine motif in the targeting peptide. The
      translocase component is encoded in Escherichia coli by an unassigned reading
      frame, yigU, disruption of which blocks the export of at least five twin-Arg
      containing precursor proteins that are predicted to bind redox cofactors, and
      hence fold, prior to translocation. The Sec pathway remains unaffected in the
      deletion strain. The gene has been designated tatC (for twin-arginine
      translocation), and we show that homologous genes are present in a range of
      bacteria, plastids, and mitochondria. These findings suggest a central role for
      TatC-type proteins in the translocation of tightly folded proteins across a
      spectrum of biological membranes.

PMID- 9660753
TI  - Specific binding of tetratricopeptide repeat proteins to the C-terminal 12-kDa
      domain of hsp90.
AB  - The molecular chaperone hsp90 in the eukaryotic cytosol interacts with a variety
      of protein cofactors. Several of these cofactors have protein domains containing
      tetratricopeptide repeat (TPR) motifs, which mediate binding to hsp90. Using a
      yeast two-hybrid screen, the 12-kDa C-terminal domain of human hsp90alpha (C90)
      was found to mediate the interaction of hsp90 with TPR-containing sequences from
      the hsp90 cofactors FKBP51/54 and FKBP52. In addition, the mitochondrial outer
      membrane protein hTOM34p was identified as a TPR-containing putative partner
      protein of hsp90. In experiments with purified proteins, the TPR-containing
      cofactor p60 (Hop) was shown to form stable complexes with hsp90. A deletion
      mutant of hsp90 lacking the C90 domain was unable to bind p60, whereas deletion
      of the approximately 25-kDa N-terminal domain of hsp90 did not affect complex
      formation. Both p60 and FKBP52 bound specifically to the C90 domain fused to
      glutathione S-transferase and competed with each other for binding. In
      reticulocyte lysate, the C90 fusion protein recognized the TPR proteins p60,
      FKBP52, and Cyp40. Thus, our results identify the C90 domain as the specific
      binding site for a set of hsp90 cofactors having TPR domains.

PMID- 9660754
TI  - Characterization of the binding site of the tripeptide intermediate D
      Phenylalanyl L-prolyl-L-valine in gramicidin S biosynthesis.
AB  - The tripeptide intermediate D-Phe-Pro-Val in the biosynthesis of gramicidin S was
      labeled by incorporation of either L-[14C]phenylalanine or L-[14C]valine in an in
      vitro biosynthetic assay. The gramicidin S synthetase 2-tripeptide complex was
      first digested with CNBr and subsequently by Staphylococcus aureus V8 protease.
      The active site peptide carrying the radioactively labeled tripeptide was
      isolated in pure form by reversed phase high performance liquid chromatography
      technology and analyzed by liquid phase sequencing, mass spectrometry, and amino
      acid analysis. It was demonstrated that D-Phe-Pro-Val is attached to the 4'
      phosphopantetheine cofactor at the thiolation center for valine of gramicidin S
      synthetase 2. In this way the attachment site of a peptide intermediate in
      nonribosomal peptide biosynthesis was identified for the first time. Our results
      are in full agreement with the multiple carrier model of nonribosomal peptide
      biosynthesis (Stein, T., Vater, J., Kruft, V., Otto, A., Wittmann-Liebold, B.,
      Franke, P., Panico, M., McDowell, R., and Morris, H. R. (1996) J. Biol. Chem.
      271, 15426-15435), which predicts that the growing peptide chain in the
      elongation process should always be bound to the thiotemplate site specific for
      its C-terminal amino acid component.

PMID- 9660755
TI  - Characterization of the human analogue of a Scrapie-responsive gene.
AB  - We have recently described a novel mRNA denominated ScRG-1, the level of which is
      increased in the brains of Scrapie-infected mice (Dandoy-Dron, F., Guillo, F.,
      Benboudjema, L., Deslys, J.-P., Lasmezas, C., Dormont, D., Tovey, M. G., and
      Dron, M. (1998) J. Biol. Chem. 273, 7691-7697). The increase in ScRG-1 mRNA in
      the brain follows the accumulation of PrPSc, the proteinase K-resistant form of
      the prion protein (PrP), and precedes the widespread neuronal death that occurs
      in late stage disease. In the present study, we have isolated a cDNA encoding the
      human counterpart of ScRG-1. Comparison of the human and mouse transcripts firmly
      established that both sequences encode a highly conserved protein of 98 amino
      acids that contains a signal peptide, suggesting that the protein may be
      secreted. Examination of the distribution of human ScRG-1 mRNA in adult and fetal
      tissues revealed that the gene was expressed primarily in the central nervous
      system as a 0.7-kilobase message and was under strict developmental control.

PMID- 9660756
TI  - Hypoxia-inducible factor 1alpha (HIF-1alpha) is a non-heme iron protein.
      Implications for oxygen sensing.
AB  - The hypoxia-inducible factor 1 complex (HIF-1) is involved in the transcriptional
      activation of several genes, like erythropoietin and vascular endothelial growth
      factor, that are responsive to the lack of oxygen. The HIF-1 complex is composed
      of two b-HLH proteins: HIF-1beta that is constitutively expressed, and HIF
      1alpha, that is present only in hypoxic cells. The HIF-1alpha subunit is
      continuously synthesized and degraded by the ubiquitin-proteasome under oxic
      conditions. Hypoxia, transition metals, iron chelators, and several antioxidants
      stabilize the HIF-1alpha protein, allowing the formation of the transcriptionally
      active HIF-1 complex. The mechanisms of oxygen sensing and the pathways leading
      to HIF-1alpha stabilization are unclear. Because the involvement of a heme
      protein oxygen sensor has been postulated, we tested the heme sensor hypothesis
      by using a luciferase-expressing cell line (B-1), that is highly responsive to
      hypoxia. Exposure of B-1 cells to carbon monoxide and heme synthesis inhibitors
      failed to show any effect on the hypoxia responsiveness of these cells,
      suggesting that heme proteins are not involved in hypoxia sensing. Measurement of
      iron in recombinantly expressed HIF-1alpha protein revealed that this protein
      binds iron in vivo. Iron binding was localized to a 129-amino acid peptide
      between sequences 529 and 658 of the HIF-1alpha protein. Although the exact
      structure of the iron center has not been yet defined, a 2:1 metal/protein molar
      ratio suggests a di-iron center, probably similar to the one found in
      hemerythrin. This finding is compatible with a model where redox reaction may
      occur directly in the iron center of the HIF-1alpha subunit, affecting its
      survival in oxic conditions.

PMID- 9660757
TI  - Phosphorylation of serine 1105 by protein kinase A inhibits phospholipase Cbeta3
      stimulation by Galphaq.
AB  - The mechanism by which protein kinase A (PKA) inhibits Galphaq -stimulated
      phospholipase C activity of the beta subclass (PLCbeta ) is unknown. We present
      evidence that phosphorylation of PLCbeta3 by PKA results in inhibition of Galphaq
      -stimulated PLCbeta3 activity, and we identify the site of phosphorylation. Two
      dimensional phosphoamino acid analysis of in vitro phosphorylated PLCbeta3
      revealed a single phosphoserine as the putative PKA site, and peptide mapping
      yielded one phosphopeptide. The residue was identified as Ser1105 by direct
      sequencing of reverse-phase high pressure liquid chromatography-isolated
      phosphopeptide and by site-directed mutagenesis. Overexpression of Galphaq with
      PLCbeta3 or PLCbeta (Ser1105--> Ala) mutant in COSM6 cells resulted in a 5-fold
      increase in [3H]phosphatidylinositol 1,4,5-trisphosphate formation compared with
      expression of Galphaq, PLCbeta3, or PLCbeta3 (Ser1105 --> Ala mutant alone.
      Whereas Galpha1-stimulated PLCbeta3, activity was inhibited by 58-71% by
      overexpression of PKA catalytic subunit, Galphaq-stimulated PLCbeta3 (Ser1105 -->
      Ala) mutant activity was not affected. Furthermore, phosphatidylinositide
      turnover stimulated by presumably Galpha1-coupled M1 muscarinic and oxytocin
      receptors was completely inhibited by pretreating cells with 8-[4
      chlorophenythio]-cAMP in RBL-2H3 cells expressing only PLCbeta3. These data
      establish that direct phosphorylation by PKA of Ser1105 in the putative G-box of
      PLCbeta3 inhibits Galphaq-stimulated PLCbeta3 activity. This can at least
      partially explain the inhibitory effect of PKA on Galphaq-stimulated
      phosphatidylinositide turnover observed in a variety of cells and tissues.

PMID- 9660758
TI  - In vitro reconstitution of Artemia satellite chromatin.
AB  - We report the characterization of an in vitro chromatin assembly system derived
      from Artemia embryos and its application to the study of AluI-113 satellite DNA
      organization in nucleosomes. The system efficiently reconstitutes chromatin
      templates by associating DNA, core histones, and H1. The polynucleosomal
      complexes show physiological spacing of repeat length 190 +/- 5 base pairs, and
      the internucleosomal distances are modulated by energy-using activities that
      contribute to the dynamics of chromatin conformation. The assembly extract was
      used to reconstitute tandemly repeated AluI-113 sequences. The establishment of
      preferred histone octamer/satellite DNA interactions was observed. In vitro, AluI
      113 elements dictated the same nucleosome translational localizations as found in
      vivo. Specific rotational constraints seem to be the central structural
      requirement for nucleosome association. Satellite dinucleosomes showed decreased
      translational mobility compared with mononucleosomes. This could be the
      consequence of interactions between rotationally positioned nucleosomes separated
      by linker DNA of uniform length. AluI-113 DNA led to weak cooperativity of
      nucleosome association in the proximal flanking regions, which decreased with
      distance. Moreover, the structural properties of satellite chromatin can spread,
      thus leading to a specific organization of adjacent nucleosomes.

PMID- 9660759
TI  - Type I phosphatidylinositol-4-phosphate 5-kinases synthesize the novel lipids
      phosphatidylinositol 3,5-bisphosphate and phosphatidylinositol 5-phosphate.
AB  - Inositol phospholipids regulate a variety of cellular processes including
      proliferation, survival, vesicular trafficking, and cytoskeletal organization.
      Recently, two novel phosphoinositides, phosphatidylinositol-3,5-bisphosphate
      (PtdIns-3,5-P2) and phosphatidylinositol- 5-phosphate (PtdIns-5-P), have been
      shown to exist in cells. PtdIns-3,5-P2, which is regulated by osmotic stress,
      appears to be synthesized by phosphorylation of PtdIns-3-P at the D-5 position.
      No evidence yet exists for how PtdIns-5-P is produced in cells. Understanding the
      regulation of synthesis of these molecules will be important for identifying
      their function in cellular signaling. To determine the pathway by which PtdIns
      3,5-P2 and Ptd-Ins-5-P might be synthesized, we tested the ability of the
      recently cloned type I PtdIns-4-P 5-kinases (PIP5Ks) alpha and beta to
      phosphorylate PtdIns-3-P and PtdIns at the D-5 position of the inositol ring. We
      found that the type I PIP5Ks phosphorylate PtdIns-3-P to form PtdIns-3,5-P2. The
      identity of the PtdIns-3,5-P2 product was determined by anion exchange high
      performance liquid chromatography analysis and periodate treatment. PtdIns-3,4-P2
      and PtdIns-3,4,5-P3 were also produced from PtdIns-3-P phosphorylation by both
      isoforms. When expressed in mammalian cells, PIP5K Ialpha and PIP5K Ibeta
      differed in their ability to synthesize PtdIns-3,5-P2 relative to PtdIns-3,4-P2.
      We also found that the type I PIP5Ks phosphorylate PtdIns to produce PtdIns-5-P
      and phosphorylate PtdIns-3,4-P2 to produce PtdIns-3,4,5-P3. Our findings suggest
      that type I PIP5Ks synthesize the novel phospholipids PtdIns-3,5-P2 and PtdIns-5
      P. The ability of PIP5Ks to produce multiple signaling molecules indicates that
      they may participate in a variety of cellular processes.

PMID- 9660760
TI  - Loss of antinociception induced by naloxone benzoylhydrazone in nociceptin
      receptor-knockout mice.
AB  - Nociceptin and nociceptin receptor, which show structural similarities to opioid
      peptides and opioid receptors, respectively, have been recently found to
      constitute a novel neuromodulatory system. In the brain, however, the
      physiological role of the modulation via the nociceptin receptor is still
      unclear. Administered nociceptin produces hyperalgesia and hypolocomotion,
      whereas the nociceptin receptor-knockout mice show no significant abnormalities
      in nociceptive thresholds and locomotion. To clarify possible involvement of the
      nociceptin receptor in the regulation of nociception and locomotion, we made use
      of the knockout mice and naloxone benzoylhydrazone (NalBzoH) identified
      originally as a ligand for opioid receptors. Experiments on the cultured cells
      transfected with the nociceptin receptor cDNA showed that NalBzoH competed with
      [3H]nociceptin binding and attenuated the nociceptin-induced inhibition of cAMP
      accumulation. Furthermore, behavioral studies demonstrated that NalBzoH
      completely inhibited nociceptin-induced hyperalgesia and hypolocomotion. It is
      therefore likely that NalBzoH can act as a potent antagonist for the nociceptin
      receptor in vivo. In wild-type mice, NalBzoH induced antinociception but did not
      affect locomotor activity. In contrast, in the knockout mice, no significant
      changes in nociception and locomotion were induced by NalBzoH. These results
      clearly suggest that the nociceptin system takes part in the physiological
      regulation of nociceptive thresholds but not in the basal modulation of
      locomotion.

PMID- 9660761
TI  - Dimeric tyrosyl-tRNA synthetase from Bacillus stearothermophilus unfolds through
      a monomeric intermediate. A quantitative analysis under equilibrium conditions.
AB  - Tyrosyl-tRNA synthetase from Bacillus stearothermophilus comprises an N-terminal
      domain (residues 1-319), which is dimeric and forms tyrosyladenylate, and a C
      terminal domain (residues 320-419), which binds the anticodon arm of tRNATyr. The
      N-terminal domain has the characteristic fold of the class I aminoacyl-tRNA
      synthetases. The unfolding of the N-terminal domain by urea at 25 degreesC under
      equilibrium conditions was monitored by its intensities of light emission at 330
      and 350 nm, the ratio of these intensities, its ellipticity at 229 nm, and its
      partition coefficient, in spectrofluorometry, circular dichroism, and size
      exclusion chromatography experiments, respectively. These experiments showed the
      existence of an equilibrium between the native dimeric state of the N-terminal
      domain, a monomeric intermediate state, and the unfolded state. The intermediate
      was compact and had secondary structure, and its tryptophan residues were
      partially buried. These properties of the intermediate and its inability to bind
      1-anilino-8-naphthalenesulfonate showed that it was not in a molten globular
      state. The variation of free energy deltaG(H2O) and its coefficient m of
      dependence on the concentration of urea were, respectively, 13.8 +/- 0.2 kcal.mol
      1 and 0.9 +/- 0.1 kcal.mol-1.M-1 for the dissociation of the native dimer and
      13.9 +/- 0.6 kcal.mol-1 and 2.5 +/- 0.1 kcal.mol-1.M-1 for the unfolding of the
      monomeric intermediate.

PMID- 9660762
TI  - Rapid, high level protein production using DNA-based Semliki Forest virus
      vectors.
AB  - Semliki Forest virus (SFV) vectors can be produced faster, and have a wider host
      range, than baculovirus vectors. However, the original SFV system requires in
      vitro manipulation of RNA. We have generated a system that is wholly DNA-based.
      Both the replicon vector, encoding SFV polymerase and the protein of interest,
      and the helper vector, encoding viral structural proteins, were modified so that
      expression was RNA polymerase II-dependent. Transfection of the modified replicon
      plasmid alone generated 20-30-fold more protein than obtained from a simple
      expression vector. Expression required the SFV replicase, which amplifies
      replicon RNA. The SFV-based vector generated 10-20-fold more protein than a
      plasmid based on Sindbis virus. Cotransfection of SFV replicon and helper vectors
      generated viral titers of around 10(6) infectious particles/ml. A single
      electroporation, plated on one 10-cm plate, generated enough virus (10(7)
      particles) to produce >500 microg of protein. Wild type, replication proficient
      virus was not detected in three tests utilizing almost 10(8) viral particles, a
      distinct advantage over a DNA Sindbis-based system in which over half the virus
      particles generated are fully infectious. The new SFV vectors significantly
      enhance the utility of this expression system.

PMID- 9660763
TI  - The Cdc42/Rac interactive binding region motif of the Wiskott Aldrich syndrome
      protein (WASP) is necessary but not sufficient for tight binding to Cdc42 and
      structure formation.
AB  - Wiskott Aldrich syndrome is a rare hereditary disease that affects cell
      morphology and signal transduction in hematopoietic cells. Different size
      fragments of the Wiskott Aldrich syndrome protein, W4, W7 and W13, were expressed
      in Escherichia coli or obtained from proteolysis. All contain the GTPase binding
      domain (GBD), also called Cdc42/Rac interactive binding region (CRIB), found in
      many putative downstream effectors of Rac and Cdc42. We have developed assays to
      measure the binding interaction between these fragments and Cdc42 employing
      fluorescent N-methylanthraniloyl-guanine nucleotide analogues. The fragments bind
      with submicromolar affinities in a GTP-dependent manner, with the largest
      fragment having the highest affinity, showing that the GBD/CRIB motif is
      necessary but not sufficient for tight binding. Rate constants for the
      interaction with W13 have been determined via surface plasmon resonance, and the
      equilibrium dissociation constant obtained from their ratio agrees with the value
      obtained by fluorescence measurements. Far UV circular dichroism spectra show
      significant secondary structure only for W13, supported by fluorescence studies
      using intrinsic protein fluorescence and quenching by acrylamide. Proton and 15N
      NMR measurements show that the GBD/CRIB motif has no apparent secondary structure
      and that the region C-terminal to the GBD/CRIB region is alpha-helical. The
      binding of Cdc42 induces a structural rearrangement of residues in the GBD/CRIB
      motif, or alternatively, the Wiskott Aldrich syndrome protein fragments have an
      ensemble of conformations, one of which is stabilized by Cdc42 binding. Thus, in
      contrast to Ras effectors, which have no conserved sequence elements but a
      defined domain structure with ubiquitin topology, Rac/Cdc42 effectors have a
      highly conserved binding region but no defined domain structure in the absence of
      the GTP-binding protein. Deviating from common belief GBD/CRIB is neither a
      structural domain nor sufficient for tight binding as regions outside this motif
      are necessary for structure formation and tight interaction with Rho/Rac
      proteins.

PMID- 9660764
TI  - Mechanisms of the mouse orphan nuclear receptor TR2-11-mediated gene suppression.
AB  - The mouse orphan nuclear receptor TR2-11 functions as a repressor for reporter
      genes containing a direct repeat-5 or direct repeat-4 hormone response element.
      The functional domains responsible for its suppressive activity are defined,
      including the DNA-binding domain and the ligand-binding domain. The C-terminal 30
      amino acid residues can be deleted without compromising its suppressive activity,
      whereas a deletion for 40 amino acids completely abolishes the suppressive
      activity and receptor dimerization, and reduces the DNA-binding affinity. Point
      mutation at three conserved leucine residues located on the predicted dimer
      interface abolishes the suppressive activity, receptor dimerization and its DNA
      binding property. However, mutation at two consecutive glutamate residues located
      within the hinge between the last two helices of the ligand-binding domain (helix
      10 and helix 11 according to the human retinoid receptor X alpha structure)
      drastically reduces its DNA-binding affinity and abrogates the suppressive
      activity without compromising its ability to dimerize, indicating that receptor
      dimerization property can be functionally uncoupled from its suppressive
      activity. A transferable, active silencing activity is encoded within the DEF
      segment of the receptor molecule, as evidenced by the suppression of a GAL4
      reporter by a chimeric protein containing the DNA-binding domain of GAL4 and the
      DEF segment of TR2-11. Moreover, the C-terminal 49 amino acid sequence is
      required for this trans-suppressive activity. It is suggested that TR2-11
      functions as a repressor, mediated by mechanisms requiring high affinity DNA
      binding, receptor dimerization, and active silencing.

PMID- 9660765
TI  - The transcriptional repressor ZFM1 interacts with and modulates the ability of
      EWS to activate transcription.
AB  - The ZFM1 protein is both a transcriptional repressor and identical to the
      splicing factor SF1. ZFM1 was shown to interact with and repress transcription
      from the glycine, glutamine, serine, and threonine-rich transcription activation
      domain of the sea urchin transcription factor, stage-specific activator protein
      (SSAP). EWS, a human protein involved in cellular transformation in Ewing's
      sarcoma tumors, contains an NH2-terminal transcriptional activation domain (NTD)
      which resembles that of SSAP in both amino acid composition and the ability to
      drive transcription to levels higher than VP16 in most cell types. Here we report
      that ZFM1 also interacts with EWS in both two-hybrid assays and glutathione S
      transferase pull-down experiments. The region on EWS which interacts with ZFM1
      maps to 37 amino acids within its NTD. Overexpression of ZFM1 in HepG2 cells
      represses the transactivation of reporter gene expression driven by Gal4-EWS-NTD
      fusion protein and this repression correlates with ZFM1 binding to EWS.
      Furthermore, two proteins, TLS and hTAFII68, which have extensive homology to
      EWS, also interact with ZFM1. Recently, it was discovered that EWS/TLS/hTAFII68
      are each present in distinct TFIID populations and EWS and hTAFII68 were also
      found to be associated with the RNA polymerase II holoenzyme. The association of
      ZFM1 with these proteins implies that one normal cellular function for ZFM1 may
      be to negatively modulate transcription of target genes coordinated by these
      cofactors.

PMID- 9660766
TI  - Reactive oxygen species released from mitochondria during brief hypoxia induce
      preconditioning in cardiomyocytes.
AB  - Reactive oxygen species (ROS) have been proposed to participate in the induction
      of cardiac preconditioning. However, their source and mechanism of induction are
      unclear. We tested whether brief hypoxia induces preconditioning by augmenting
      mitochondrial generation of ROS in chick cardiomyocytes. Cells were
      preconditioned with 10 min of hypoxia, followed by 1 h of simulated ischemia and
      3 h of reperfusion. Preconditioning decreased cell death from 47 +/- 3% to 14 +/-
      2%. Return of contraction was observed in 3/3 preconditioned versus 0/6 non
      preconditioned experiments. During induction, ROS oxidation of the probe
      dichlorofluorescin (sensitive to H2O2) increased approximately 2.5-fold. As a
      substitute for hypoxia, the addition of H2O2 (15 micromol/liter) during normoxia
      also induced preconditioning-like protection. Conversely, the ROS signal during
      hypoxia was attenuated with the thiol reductant 2-mercaptopropionyl glycine, the
      cytosolic Cu,Zn-superoxide dismutase inhibitor diethyldithiocarbamic acid, and
      the anion channel inhibitor 4,4'-diisothiocyanato-stilbene-2,2'-disulfonate, all
      of which also abrogated protection. ROS generation during hypoxia was attenuated
      by myxothiazol, but not by diphenyleneiodonium or the nitric-oxide synthase
      inhibitor L-nitroarginine. We conclude that hypoxia increases mitochondrial
      superoxide generation which initiates preconditioning protection. Furthermore,
      mitochondrial anion channels and cytosolic dismutation to H2O2 may be important
      steps for oxidant induction of hypoxic preconditioning.

PMID- 9660767
TI  - Biosynthesis of the diterpene verrucosan-2beta-ol in the phototrophic eubacterium
      Chloroflexus aurantiacus. A retrobiosynthetic NMR study.
AB  - The biosynthesis of verrucosan-2beta-ol in the green phototrophic eubacterium
      Chloroflexus aurantiacus was investigated by in vivo incorporation of singly or
      doubly 13C-labeled acetate. The 13C labeling of the isolated diterpene was
      analyzed by one- and two-dimensional NMR spectroscopy. The 13C-labeling patterns
      of verrucosan-2beta-ol were compared with the labeling patterns of intermediary
      metabolites (acetyl-CoA, pyruvate, and glyceraldehyde 3-phosphate) which were
      deduced from amino acids and nucleosides by retrobiosynthetic analysis. The
      results show that verrucosan-2beta-ol is synthesized via mevalonate and not via
      the deoxyxylulose pathway, which was discovered recently in some eubacteria,
      algae, and plants. A scheme for the formation of the unusual tetracyclic ring
      system is offered. The cyclization process is initiated by the solvolysis of
      pyrophosphate from geranyllinaloyl pyrophosphate and the mechanism involves a
      Wagner-Meerwein rearrangement, a 1,5-hydride shift, and a cyclopropylcarbinyl to
      cyclopropylcarbinyl rearrangement.

PMID- 9660768
TI  - The repressor protein, Bm3R1, mediates an adaptive response to toxic fatty acids
      in Bacillus megaterium.
AB  - Bm3R1 is a helix-turn-helix transcriptional repressor from Bacillus megaterium
      whose binding to DNA is inhibited by fatty acids and a wide range of compounds
      that modulate lipid metabolism. The inactivation of Bm3R1/DNA binding activity
      results in the activation of transcription of the operon encoding a fatty acid
      hydroxylase, cytochrome P450 102. The metabolic role of this operon is unknown.
      It is possible that it is involved in the synthesis of modified fatty acids as
      part of normal cellular metabolism or may represent a protective mechanism by
      which B. megaterium detoxifies harmful foreign lipids. In this report we
      demonstrate that polyunsaturated fatty acids (PUFA) activate the transcription of
      the CYP102 operon. These PUFA are the most potent activators of the CYP102 operon
      observed to date, and we show that their effects are due to binding directly to
      Bm3R1. In addition, cultures that have been treated with the CYP102 inducer,
      nafenopin, are protected against PUFA toxicity. Resistance to PUFA toxicity is
      also seen in a Bm3R1-deficient strain that constitutively expresses CYP102. The
      resistant phenotype of this Bm3R1 mutant strain is reversed by specific chemical
      inactivation of CYP102. These data demonstrate that Bm3R1 can act as a direct
      sensor of toxic fatty acids and, in addition, provide the first direct evidence
      of fatty acids binding to a prokaryotic transcription factor.

PMID- 9660769
TI  - Tumor necrosis factor-alpha-induced cell killing and activation of transcription
      factor NF-kappaB are uncoupled in L929 cells.
AB  - The induction of transcription factor NF-kappaB has been shown to counteract
      tumor necrosis factor (TNF)-alpha-induced cell death in various cell types. In
      this study, we investigated the role of NF-kappaB for TNF-alpha-triggered cell
      death in the widely used mouse cell line L929 by various approaches. Inhibition
      of the mitochondrial permeability transition by bongkrekic acid impaired TNF
      alpha-induced cell death without affecting the activity of NF-kappaB. The
      reduction of NF-kappaB-mediated gene expression by the synthetic steroid
      dexamethasone was associated with a decrease in TNF-alpha-mediated cell killing,
      suggesting that NF-kappaB does not protect L929 cells from TNF-alpha-induced cell
      death. This concept was reinforced by experiments employing L929 cell lines
      stably overexpressing a transdominant negative form of IkappaB-alpha. These cell
      lines were unable to activate NF-kappaB and to inducibly express the IL-6 gene,
      but they showed the same susceptibility toward TNF-alpha-mediated cell death as
      L929 wild-type cells.

PMID- 9660770
TI  - Aerolysin induces G-protein activation and Ca2+ release from intracellular stores
      in human granulocytes.
AB  - Aerolysin is a pore-forming toxin that plays a key role in the pathogenesis of
      Aeromonas hydrophila infections. In this study, we have analyzed the effect of
      aerolysin on human granulocytes (HL-60 cells). Proaerolysin could bind to these
      cells, was processed into active aerolysin, and led to membrane depolarization,
      indicating that granulocytes are potential targets for this toxin. Fura-2
      measurements were used to analyze the effect of aerolysin on cytosolic [Ca2+]
      homeostasis. As expected for a pore-forming toxin, aerolysin addition led to Ca2+
      influx across the plasma membrane. In addition, the toxin triggered Ca2+ release
      from agonist and thapsigargin-sensitive intracellular Ca2+ stores. This Ca2+
      release was independent of the aerolysin-induced Ca2+ influx and occurred in two
      kinetically distinct phases: an initial rapid and transient phase and a second,
      more sustained, phase. The first, but not the second phase was sensitive to
      pertussis toxin. Activation of pertussis toxin-sensitive G-proteins appeared to
      be a consequence of pore formation, rather than receptor activation through
      aerolysin-binding, as it: (i) was not observed with a binding competent,
      insertion-incompetent aerolysin mutant, (ii) had a marked lag time, and (iii) was
      also observed in response to other bacterial pore-forming toxins (staphylococcal
      alpha-toxin, streptolysin O) which are thought to bind to different receptors. G
      protein activation through pore-forming toxins stimulated cellular functions, as
      evidenced by pertussis toxin-sensitive chemotaxis. Our results demonstrate that
      granulocytes are potential target cells for aerolysin and that in these cells,
      Ca2+ signaling in response to a pore-forming toxin involves G-protein-dependent
      cell activation and Ca2+ release from intracellular stores.

PMID- 9660771
TI  - Affinity purification of Helicobacter pylori urease. Relevance to gastric mucin
      adherence by urease protein.
AB  - A simple, reproducible and high yield method of Helicobacter pylori urease enzyme
      purification was developed using a heparinoid (Cellufine sulfate) affinity gel.
      The purification method involved two sequential steps using the same gel that
      takes advantage of the differential affinity of urease to the heparinoid at two
      levels of hydrogen ion concentration. SDS-polyacrylamide gel electrophoresis
      analysis of affinity-purified urease revealed two major protein bands with about
      62- and 30-kDa molecular mass. When whole cell lysates of clinical and laboratory
      strains of H. pylori were probed by Western blot, anti-urease hyperimmune serum
      produced by affinity-purified urease in rabbit recognized only the two bands
      corresponding to the urease A and B subunits. To probe the molecular relevance of
      affinity gel adherence to mucin adherence, the purified urease was derivatized
      with N-hydroxysuccinimidobiotin and used in adherence assays. Competitive
      inhibition tests revealed commonality of urease receptors among gastric mucin,
      heparin, and heparinoid. Composite data on adherence kinetics modulated by pH,
      salt, incubation time, and concentration of urease or mucin were indicative of
      conformation-dependent ligand-receptor interaction.

PMID- 9660772
TI  - Aspirin inhibition and acetylation of the plant cytochrome P450, allene oxide
      synthase, resembles that of animal prostaglandin endoperoxide H synthase.
AB  - The enzymatic reactions leading to octadecanoid lipid signaling intermediates in
      plants are similar to those of animals and are inhibited by nonsteroidal anti
      inflammatory drugs (NSAIDs) such as salicylic acid and aspirin. In animals,
      NSAIDs inhibit the cyclooxygenase (COX) activity of prostaglandin endoperoxide H
      synthase, which ultimately blocks the formation of prostaglandins. In plants,
      NSAIDs block the formation of 12-oxo-phytodienoic acid and jasmonates, which are
      the equivalent signaling compounds. In this study we show that NSAIDs act as
      competitive inhibitors of allene oxide synthase (AOS), the cytochrome P450 that
      initiates plant oxylipin synthesis. We also show that aspirin causes the time
      dependent inhibition and acetylation of AOS, which leads the irreversible
      inactivation of this enzyme. This inhibition and acetylation superficially
      resembles that observed for the inactivation of COX in animals. In AOS, aspirin
      acetylates three serine residues near the C-terminal region that appear to be
      highly conserved among AOS sequences from other plants but are not conserved
      among "classical" type P450s. The role of these serine residues is unclear.
      Unlike animal COX, where acetylation of a single serine residue within the
      substrate channel leads to inactivation of prostaglandin endoperoxide H synthase,
      the three serine residues in AOS are not thought to line the putative substrate
      channel. Thus, inhibition by aspirin may be by a different mechanism. It is
      possible that aspirin and related NSAIDs could inhibit other P450s that have
      motifs similar to AOS and consequently serve as potential biochemical targets for
      this class of drugs.

PMID- 9660773
TI  - Oncogenic src, raf, and ras stimulate a hypertrophic pattern of gene expression
      and increase cell size in neonatal rat ventricular myocytes.
AB  - In response to hormones and growth factors, cultured neonatal ventricular
      myocytes increase in profile, exhibit myofibrillogenesis, and re-express genes
      whose expression is normally restricted to the fetal stage of ventricular
      development. These include atrial natriuretic factor (ANF), beta-myosin heavy
      chain (beta-MHC), and skeletal muscle (SkM)-alpha-actin. By using luciferase
      reporter plasmids, we examined whether oncogenes that activate the extracellular
      signal-regulated kinase cascade (srcF527, Ha-rasV12, and v-raf) increased
      expression of "fetal" genes. Transfection of myocytes with srcF527 stimulated
      expression of ANF, SkM-alpha-actin, and beta-MHC by 62-, 6.7-, and 50-fold,
      respectively, but did not induce DNA synthesis. Stimulation of ANF expression by
      srcF527 was greater than by Ha-rasV12, which in turn was greater than by v-raf.
      General gene expression was also increased but to a lesser extent. The response
      to srcF527 was inhibited by dominant-negative Ha-rasN17. Myocyte area was
      increased by srcF527, Ha-rasV12, and v-raf, and although it altered myocyte
      morphology by causing a pseudopodial appearance, srcF527 did not detectably
      increase myofibrillogenesis either alone or in combination with Ha-rasV12. A
      kinase-dead src mutant increased myocyte size to a much lesser extent than
      srcF527 and also did not inhibit ANF-luciferase expression in response to
      phenylephrine. We conclude that members of the Src family of tyrosine kinases may
      be important in mediating the transcriptional changes occurring during cardiac
      myocyte hypertrophy and that Ras and Raf may be downstream effectors.

PMID- 9660774
TI  - Activities of recombinant human cytochrome P450c27 (CYP27) which produce
      intermediates of alternative bile acid biosynthetic pathways.
AB  - The primary physiological significance of cytochrome P450c27 (CYP27) has been
      associated with its role in the degradation of the side chain of C27 steroids in
      the hepatic bile acid biosynthesis pathway, which begins with 7alpha
      hydroxylation of cholesterol in liver. However, recognition that in humans
      P450c27 is a widely or ubiquitously expressed mitochondrial P450, and that there
      are alternative pathways of bile acid synthesis which begin with 27-hydroxylation
      of cholesterol catalyzed by P450c27, suggests the need to reevaluate the role of
      this enzyme and its catalytic properties. 27-Hydroxycholesterol was thought to be
      the only product formed upon reaction of P450c27 with cholesterol. However, the
      present study demonstrates that recombinant human P450c27 is also able to further
      oxidize 27-hydroxycholesterol giving first an aldehyde and then 3beta-hydroxy-5
      cholestenoic acid. Kinetic data indicate that in a reconstituted system, after 27
      hydroxycholesterol is formed from cholesterol, it is released from the P450 and
      then competes with cholesterol for reentry the enzyme active site for further
      oxidation. Under subsaturating substrate concentrations, the efficiencies of
      oxidation of 27-hydroxycholesterol and 3beta-hydroxy-5-cholestenal to the acid by
      human P450c27 are greater than the efficiency of hydroxylation of cholesterol to
      27-hydroxycholesterol indicating that the first hydroxylation step in the overall
      conversion of cholesterol into 3beta-hydroxy-5-cholestenoic acid is rate
      limiting. Interestingly, 3beta-hydroxy-5-cholestenoic acid was found to be
      further metabolized by the recombinant human P450c27, giving two monohydroxylated
      products with the hydroxyl group introduced at different positions on the steroid
      nucleus.

PMID- 9660775
TI  - Structure and expression of the mRNA encoding a novel fibroblast growth factor,
      FGF-18.
AB  - We isolated the cDNA encoding a novel member (207 amino acids) of the fibroblast
      growth factor (FGF) family from rat embryos. Because this protein is the 18th
      documented member of the FGF family, we tentatively termed it FGF-18. We have
      also determined mouse and human FGF-18 with high amino acid identity (99.5 and
      99.0%) to rat FGF-18, respectively. Among FGF family members, FGF-18 is most
      similar (52.7% amino acid identity) to FGF-8 and FGF-17. FGF-18 has a typical
      signal sequence at its amino terminus. Recombinant rat FGF-18, which was
      efficiently secreted by High Five insect cells infected with recombinant
      baculovirus containing the cDNA, induced neurite outgrowth in PC12 cells. The
      expression of FGF-18 mRNA was examined in adult rat tissues and embryos by
      Northern blotting analysis and in situ hybridization. FGF-18 mRNA of
      approximately 2. 7 kilobases was preferentially detected in the lung among adult
      rat tissues examined. In rat embryos, FGF-18 mRNA was detected in several
      discrete regions at embryonic days 14.5 and 19.5 but not at E10.5. The temporal
      and spatial patterns of FGF-18 mRNA expression in embryos are quite different
      from those of FGF-8 and FGF-17 mRNAs reported. The present results indicate that
      FGF-18 is a unique secreted signaling molecule in the adult lung and developing
      tissues.

PMID- 9660776
TI  - p42/p44 MAP kinase module plays a key role in the transcriptional regulation of
      the vascular endothelial growth factor gene in fibroblasts.
AB  - Vascular Endothelial Growth Factor (VEGF) is a potent mitogen for vascular
      endothelial cells that has been implicated in tumor neovascularization. We show
      that, in hamster fibroblasts (CCL39 cells), VEGF mRNAs are expressed at low
      levels in serum-deprived or exponentially growing cells, whereas it is rapidly
      induced after stimulation of quiescent cells with serum. CCL39 derivatives,
      transformed with Polyoma virus or with active members of the p42/p44 mitogen
      activated protein (MAP) kinase pathway, Gly/Val point mutant of Ras at position
      12 (Ras-Val12), MKK1 in which Ser218 and Ser222 were mutated to Asp (MKK1
      SS/DD)), express very high levels of VEGF mRNA. To analyze the contribution of
      the p42/p44MAP kinase in this induction, we used the CCL39-derived cell line (Raf
      1:ER) expressing an estradiol-activable Raf-1. We show a time and an estradiol
      dose-dependent up-regulation of VEGF mRNA clearly detectable after 2 h of
      stimulation. The induction of VEGF mRNA in response to conditioned activation of
      Raf-1 is reverted by an inhibitor of MKK1, PD 098059, highlighting a specific
      role for the p42/p44 MAP kinase pathway in VEGF expression. Interestingly,
      hypoxia has an additive effect on VEGF induction in CCL39 cells stimulated by
      serum or in Raf-1:ER cells stimulated by estradiol. In contrast to VEGF, the
      isoforms VEGF-B and VEGF-C are poorly regulated by growth and oncogenic factors.
      We have identified a GC-rich region of the VEGF promoter between -88 and -66 base
      pairs which contains all the elements responsible of its up-regulation by
      constitutive active Ras or MKK1-SS/DD. By mutation of the putative binding sites
      and electrophoretic mobility supershift experiments, we showed that the GC-rich
      region constitutively binds Sp1 and AP-2 transcription factors. Furthermore,
      following activation of the p42/p44 MAP kinase module, the binding of Sp1 and AP
      2 is increased in the complexes formed in this region of the promoter.
      Altogether, these data suggest that hypoxia and p42/p44 MAP kinase independently
      play a key role in the regulation of the VEGF expression.

PMID- 9660777
TI  - Dissociation of GLUT4 translocation and insulin-stimulated glucose transport in
      transgenic mice overexpressing GLUT1 in skeletal muscle.
AB  - Overexpression of the human GLUT1 glucose transporter protein in skeletal muscle
      of transgenic mice results in large increases in basal glucose transport and
      metabolism, but impaired stimulation of glucose transport by insulin,
      contractions, or hypoxia (Gulve, E. A., Ren, J.-M., Marshall, B. A., Gao, J.,
      Hansen, P. A., Holloszy, J. O. , and Mueckler, M. (1994) J. Biol. Chem. 269,
      18366-18370). This study examined the relationship between glucose transport and
      cell-surface glucose transporter content in isolated skeletal muscle from wild
      type and GLUT1-overexpressing mice using 2-deoxyglucose, 3-O-methylglucose, and
      the 2-N-[4-(1-azi-2,2, 2-trifluoroethyl)benzoyl]-1,3-bis(D-mannos-4-yloxy)-2
      propyl amine exofacial photolabeling technique. Insulin (2 milliunits/ml)
      stimulated a 3-fold increase in 2-deoxyglucose uptake in extensor digitorum
      longus muscles of control mice (0.47 +/- 0.07 micromol/ml/20 min in basal muscle
      versus 1.44 micromol/ml/20 min in insulin-stimulated muscle; mean +/- S.E.).
      Insulin failed to increase 2-deoxyglucose uptake above basal rates in muscles
      overexpressing GLUT1 (4.00 +/- 0.40 micromol/ml/20 min in basal muscle versus
      3.96 +/- 0.37 micromol/ml/20 min in insulin-stimulated muscle). A similar lack of
      insulin stimulation in muscles overexpressing GLUT1 was observed using 3-O
      methylglucose. However, the magnitude of the insulin-stimulated increase in cell
      surface GLUT4 photolabeling was nearly identical (approximately 3-fold) in wild
      type and GLUT1-overexpressing muscles. This apparently normal insulin-stimulated
      translocation of GLUT4 in GLUT1-overexpressing muscle was confirmed by
      immunoelectron microscopy. Our findings suggest that GLUT4 activity at the plasma
      membrane can be dissociated from the plasma membrane content of GLUT4 molecules
      and thus suggest that the intrinsic activity of GLUT4 is subject to regulation.

PMID- 9660778
TI  - Control of myocardial contractile function by the level of beta-adrenergic
      receptor kinase 1 in gene-targeted mice.
AB  - We studied the effect of alterations in the level of myocardial beta-adrenergic
      receptor kinase betaARK1) in two types of genetically altered mice. The first
      group is heterozygous for betaARK1 gene ablation, betaARK1(+/-), and the second
      is not only heterozygous for betaARK1 gene ablation but is also transgenic for
      cardiac-specific overexpression of a betaARK1 COOH-terminal inhibitor peptide,
      betaARK1(+/-)betaARKct. In contrast to the embryonic lethal phenotype of the
      homozygous betaARK1 knockout (Jaber, M., Koch, W. J., Rockman, H. A., Smith, B.,
      Bond, R. A., Sulik, K., Ross, J., Jr., Lefkowitz, R. J., Caron, M. G., and Giros,
      B. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 12974-12979), betaARK1(+/-) mice
      develop normally. Cardiac catheterization was performed in mice and showed a
      stepwise increase in contractile function in the betaARK1(+/-) and betaARK1(+/
      )betaARKct mice with the greatest level observed in the betaARK1(+/-)betaARKct
      animals. Contractile parameters were measured in adult myocytes isolated from
      both groups of gene-targeted animals. A significantly greater increase in percent
      cell shortening and rate of cell shortening following isoproterenol stimulation
      was observed in the betaARK1(+/-) and betaARK1(+/-)betaARKct myocytes compared
      with wild-type cells, indicating a progressive increase in intrinsic
      contractility. These data demonstrate that contractile function can be modulated
      by the level of betaARK1 activity. This has important implications in disease
      states such as heart failure (in which betaARK1 activity is increased) and
      suggests that betaARK1 should be considered as a therapeutic target in this
      situation. Even partial inhibition of betaARK1 activity enhances beta-adrenergic
      receptor signaling leading to improved functional catecholamine responsiveness.

PMID- 9660779
TI  - Dexamethasone is a novel potent inducer of connective tissue growth factor
      expression. Implications for glucocorticoid therapy.
AB  - Due to its potent effect on fibroblast proliferation and extracellular matrix
      deposition, connective tissue growth factor (CTGF) seems to play an important
      role in the pathogenesis of fibrotic disease. Since glucocorticoids are
      frequently used for the therapy of these disorders, we determined a potential
      effect of these steroids on CTGF expression. In cultured fibroblasts, a striking
      induction of CTGF expression was observed after dexamethasone treatment and
      occurred in a time- and dose-dependent manner. This effect was obviously not
      mediated by the CTGF inducer transforming growth factor-beta1, since expression
      of this factor was down-regulated by the glucocorticoid. Most importantly, CTGF
      expression levels also increased substantially in various tissues and organs by
      systemic glucocorticoid treatment of mice. After cutaneous injury, a strong
      induction of CTGF expression was seen in the wounds of nontreated mice. However,
      no further increase in the levels of CTGF mRNA occurred in wounded skin compared
      with unwounded skin of glucocorticoid-treated animals, suggesting the presence of
      other factors in the wound that might compensate for the effect of the steroids.
      Tumor necrosis factor-alpha was identified as a possible mediator of this effect
      because this factor suppressed CTGF expression in cultured fibroblasts and also
      blocked the glucocorticoid-induced CTGF production by these cells. These findings
      indicate that glucocorticoids stimulate CTGF expression in normal tissues and
      organs but not in highly inflamed areas.

PMID- 9660780
TI  - A novel mechanism-based inhibitor (6'-bromo-5', 6'-didehydro-6'-deoxy-6'
      fluorohomoadenosine) that covalently modifies human placental S
      adenosylhomocysteine hydrolase.
AB  - Most inhibitors of S-adenosylhomocysteine (AdoHcy) hydrolase function as
      substrates for the "3'-oxidative activity" of the enzyme and convert the enzyme
      from its active form (NAD+) to its inactive form (NADH) (Liu, S., Wolfe, M. S.,
      and Borchardt, R. T. (1992) Antivir. Res. 19, 247-265). In this study, we
      describe the effects of a mechanism-based inhibitor, 6'-bromo-5', 6'-didehydro-6'
      deoxy-6'-fluorohomoadenosine (BDDFHA), which functions as a substrate for the "6'
      hydrolytic activity" of the enzyme with subsequent formation of a covalent
      linkage with the enzyme. Incubation of human placental AdoHcy hydrolase with
      BDDFHA results in a maximum inactivation of 83% with the remaining enzyme
      activity exhibiting one-third of the kcat value of the native enzyme. This
      partial inactivation is concomitant with the release of both Br- and F- ions and
      the formation of adenine (Ade). The enzyme can be covalently labeled with [8
      3H]BDDFHA, resulting in a stoichiometry of 2 mol of BDDFHA/mol of the tetrameric
      enzyme. The 3H-labeled enzyme retains its original NAD+/NADH content. Tryptic
      digestion and subsequent protein sequencing of the [8-3H]BDDFHA-labeled enzyme
      revealed that Arg196 is the residue that is associated with the radiolabeled
      inhibitor. The partition ratio of the Ade formation (nonlethal event) to covalent
      acylation (lethal event) is approximately 1:1. From these experimental results, a
      possible mechanism by which BDDFHA inactivates AdoHcy hdyrolase is proposed:
      enzyme-mediated water addition at the C-6' position of BDDFHA followed by
      elimination of Br- ion results in the formation of homoAdo 6'-carboxyl fluoride
      (HACF). HACF then partitions in two ways: (a) attack by a proximal nucleophile
      (Arg196) to form an amide bond after expulsion of F- ion (lethal event) or (b)
      depurination to form Ade and hexose-derived 6-carboxyl fluoride (HDCF), which is
      further hydrolyzed to hexose-derived 6-carboxylic acid (HDCA) and F- ion
      (nonlethal event).

PMID- 9660781
TI  - Identification of a membrane-associated inhibitor(s) of epidermal growth factor
      induced signal transducer and activator of transcription activation.
AB  - Many growth factors, including epidermal growth factor (EGF), can activate the
      signal transducer and activator of transcription (STAT) signaling pathway. Here,
      we demonstrate that STAT activation by EGF treatment is conditional. EGF
      activates STAT1 and STAT3 in A431 but not in HeLa and PC12 cells. Using a
      reconstituted in vitro STAT activation system, we have identified and partially
      purified a potential inhibitor (s) that is membrane-associated and can block STAT
      activation induced by EGF in vitro. However, this inhibitor has no effect on STAT
      complexes after they are formed. We have further shown that this inhibitor(s)
      also exists in many other cancer cell lines, suggesting that blocking the STAT
      activation during growth factor signal transduction may play a significant role
      in the development of many kinds of cancers.

PMID- 9660782
TI  - The human homolog of Saccharomyces cerevisiae CDC45.
AB  - In budding yeast Saccharomyces cerevisiae CDC45 is an essential gene required for
      initiation of DNA replication. A structurally related protein Tsd2 is necessary
      for DNA replication in Ustilago maydis. We have identified and cloned the gene
      for a human protein homologous to the fungal proteins. The human gene CDC45L is
      30 kilobases long and contains 15 introns. The 16 exons encode a protein of 566
      amino acids. The human protein is 52 and 49.5% similar to CDC45p and Tsd2p,
      respectively. The level of CDC45L mRNA peaks at G1-S transition, but total
      protein amount remains constant throughout the cell cycle. Consistent with a role
      of CDC45L protein in the initiation of DNA replication it co-immunoprecipitates
      from cell extracts with a putative replication initiator protein, human ORC2L. In
      addition, subcellular fractionation indicates that the association of the protein
      with the nuclear fraction becomes labile as S phase progresses. The CDC45L gene
      is located to chromosome 22q11.2 region by cytogenetics and by fluorescence in
      situ hybridization. This region, known as DiGeorge syndrome critical region, is a
      minimal area of 2 megabases, which is consistently deleted in DiGeorge syndrome
      and related disorders. The syndrome is marked by parathyroid hypoplasia, thymic
      aplasia, or hypoplasia and congenital cardiac abnormalities. CDC45L is the first
      gene mapped to the DiGeorge syndrome critical region interval whose loss may
      negatively affect cell proliferation.

PMID- 9660783
TI  - Disruption of the Saccharomyces cerevisiae FAT1 gene decreases very long-chain
      fatty acyl-CoA synthetase activity and elevates intracellular very long-chain
      fatty acid concentrations.
AB  - Activation of fatty acids to their coenzyme A derivatives is necessary for
      subsequent metabolism. Very long-chain fatty acids, which accumulate in tissues
      of patients with X-linked adrenoleukodystrophy, are activated by very long-chain
      acyl-CoA synthetase (VLCS) normally found in peroxisomes and microsomes. We
      identified a candidate yeast VLCS gene (FAT1), previously identified as encoding
      a fatty acid transport protein, by its homology to rat liver peroxisomal VLCS.
      Disruption of this gene decreased, but did not abolish, cellular VLCS activity.
      Fractionation studies showed that VLCS activity, but not long-chain acyl-CoA
      synthetase activity, was reduced to about 40% of wild-type level in both 27,000 x
      g supernatant and pellet fractions. Separation of organelles in the pellet
      fraction by density gradient centrifugation revealed that VLCS activity was
      associated with peroxisomes and microsomes but not mitochondria. FAT1 deletion
      strains exhibited decreased growth on medium containing dextrose, oleic acid, and
      cerulenin, an inhibitor of fatty acid synthesis. FAT1 deletion strains grown on
      either dextrose or oleic acid medium accumulated very long-chain fatty acids.
      Compared with wild-type yeast, C22:0, C24:0, and C26:0 levels were increased
      approximately 20-, 18-, and 3-fold in deletion strains grown on dextrose, and 2-,
      7-, and 5-fold in deletion strains grown on oleate. Long-chain fatty acid levels
      in wild-type and deletion strains were not significantly different. All
      biochemical defects in FAT1 deletion strains were restored to normal after
      functional complementation with the FAT1 gene. The level of VLCS activity
      measured in both wild-type and deletion yeast strains transformed with FAT1 cDNA
      paralleled the level of expression of the transgene. The extent of both the
      decrease in peroxisomal VLCS activity and the very long-chain fatty acid
      accumulation in the yeast FAT1 deletion model resembles that observed in cells
      from X-linked adrenoleukodystrophy patients. These studies suggest that the FAT1
      gene product has VLCS activity that is essential for normal cellular very long
      chain fatty acid homeostasis.

PMID- 9660784
TI  - Biochemical characterization of the NF-Y transcription factor complex during B
      lymphocyte development.
AB  - The transcription factor, NF-Y, plays a critical role in tissue-specific major
      histocompatibility complex class II gene transcription. In this report the
      biochemical properties of the heterotrimeric NF-Y complex have been characterized
      during stage-specific B-cell development, and in several class II- mutant B-cell
      lines, which represent distinct bare lymphocyte syndrome class II genetic
      complementation groups. The NF-Y complex derived from class II+ mature B-cells
      bound with high affinity to anion exchangers, and eluted as an intact trimeric
      complex, whereas, NF-Y derived from class II- plasma B-cells, and from bare
      lymphocyte syndrome group II cell lines, RJ2.2.5 and RM3, dissociated into
      discrete NF-YA and NF-YB:C subunit fractions. Recombination of the MPC11 plasma B
      cell derived NF-Y A:B:C complex with the low molecular mass protein fraction, NF
      Y-associated factors (YAFs), derived from mature A20 B-cell nuclei, conferred
      high affinity anion exchange binding to NF-Y as an intact trimeric complex.
      Recombination of the native NF-YA:B:C complex with the transcriptional cofactor,
      PC4, likewise conferred high affinity NF-Y binding to anion exchangers, and
      stabilized NF-Y interaction with CCAAT-box DNA motifs in vitro. Interaction
      between PC4 and NF-Y was mapped to the C-terminal region of PC4, and the subunit
      interaction subdomain of the highly conserved DNA binding-subunit interaction
      domain (DBD) of NF-YA. These results suggest that in class II+ mature B-cells NF
      Y is associated with the protein cofactor, PC4, which may play an important role
      in NF-Y-mediated transcriptional control of class II genes.

PMID- 9660785
TI  - Ca2+ transport by reconstituted synaptosomal ATPase is associated with H+
      countertransport and net charge displacement.
AB  - The synaptosomal plasma membrane Ca2+-ATPase (PMCA) purified from pig brain was
      reconstituted with liposomes prepared by reverse phase evaporation at a lipid to
      protein ratio of 150/1 (w/w). ATP-dependent Ca2+ uptake and H+ ejection by the
      reconstituted proteoliposomes were demonstrated by following light absorption and
      fluorescence changes undergone by arsenazo III and 8-hydroxy-1,3, 6-pyrene
      trisulfonate, respectively. Ca2+ uptake was increased up to 2-3-fold by the H+
      ionophore carbonyl cyanide p-trifluoromethoxyphenylhydrazone, consistent with
      relief of an inhibitory transmembrane pH gradient (i.e. lumenal alkalinization)
      generated by H+ countertransport. The stoichiometric ratio of Ca2+/H+
      countertransport was 1.0/0.6, and the ATP/Ca2+ coupling stoichiometry was 1/1 at
      25 degrees C. The electrogenic character of the Ca2+/H+ countertransport was
      demonstrated by measuring light absorption changes undergone by oxonol VI. It was
      shown that a 20 mV steady state potential (positive on the lumenal side) was
      formed as a consequence of net charge transfer associated with the 1/1 Ca2+/H+
      countertransport. Calmodulin stimulated ATPase activity, Ca2+ uptake, and H+
      ejection, demonstrating that these parameters are linked by the same mechanism of
      PMCA regulation.

PMID- 9660786
TI  - Splice variants of the Drosophila PS2 integrins differentially interact with RGD
      containing fragments of the extracellular proteins tiggrin, ten-m, and D-laminin
      2.
AB  - Two new potential ligands of the Drosophila PS2 integrins have been characterized
      by functional interaction in cell culture. These potential ligands are a new
      Drosophila laminin alpha2 chain encoded by the wing blister locus and Ten-m, an
      extracellular protein known to be involved in embryonic pattern formation. As
      with previously identified PS2 ligands, both contain RGD sequences, and RGD
      containing fragments of these two proteins (DLAM-RGD and TENM-RGD) can support
      PS2 integrin-mediated cell spreading. In all cases, this spreading is inhibited
      specifically by short RGD-containing peptides. As previously found for the PS2
      ligand tiggrin (and the tiggrin fragment TIG-RGD), TENM-RGD induces maximal
      spreading of cells expressing integrin containing the alphaPS2C splice variant.
      This is in contrast to DLAM-RGD, which is the first Drosophila polypeptide shown
      to interact preferentially with cells expressing the alphaPS2 m8 splice variant.
      The betaPS integrin subunit also varies in the presumed ligand binding region as
      a result of alternative splicing. For TIG-RGD and TENM-RGD, the beta splice
      variant has little effect, but for DLAM-RGD, maximal cell spreading is supported
      only by the betaPS4A form of the protein. Thus, the diversity in PS2 integrins
      due to splicing variations, in combination with diversity of matrix ligands, can
      greatly enhance the functional complexity of PS2-ligand interactions in the
      developing animal. The data also suggest that the splice variants may alter
      regions of the subunits that are directly involved in ligand interactions, and
      this is discussed with respect to models of integrin structure.

PMID- 9660787
TI  - The cytoplasmic F-box binding protein SKP1 contains a novel pentasaccharide
      linked to hydroxyproline in Dictyostelium.
AB  - SKP1 is involved in the ubiquitination of certain cell cycle and nutritional
      regulatory proteins for rapid turnover. SKP1 from Dictyostelium has been known to
      be modified by an oligosaccharide containing Fuc and Gal, which is unusual for a
      cytoplasmic or nuclear protein. To establish how it is glycosylated, SKP1 labeled
      with [3H]Fuc was purified to homogeneity and digested with endo-Lys-C. A single
      radioactive peptide was found after two-dimensional high performance liquid
      chromatography. Analysis in a quadrupole time-of-flight mass spectrometer
      revealed a predominant ion with a novel mass. Tandem mass spectrometry analysis
      yielded a set of daughter ions which identified the peptide and showed that it
      was modified at Pro-143. A second series of daughter ions showed that Pro-143 was
      hydroxylated and derivatized with a potentially linear pentasaccharide, Hex-->Hex
      ->Fuc-->Hex-->HexNAc-->(HyPro). The attachment site was confirmed by Edman
      degradation. Gas chromatography-mass spectrometry analysis of trimethylsilyl
      derivatives of overexpressed SKP1 after methanolysis showed the HexNAc to be
      GlcNAc. Exoglycosidase digestions of the glycopeptide from normal SKP1 and from a
      fucosylation mutant, followed by matrix-assisted laser desorption time-of-flight
      mass spectrometry analysis, showed that the sugar chain consisted of D-Galpalpha1
      ->6-D-Galpalpha1-->L-Fucpalpha1-->2-D- Galpbeta1--> 3GlcNAc. Matrix-assisted
      laser-desorption time-of-flight mass spectrometry analysis of all SKP1 peptides
      resolved by reversed phase-high performance liquid chromatography showed that
      SKP1 was only partially hydroxylated at Pro-143 and that all hydroxylated SKP1
      was completely glycosylated. Thus SKP1 is variably modified by an unusual linear
      pentasaccharide, suggesting the localization of a novel glycosylation pathway in
      the cytoplasm.

PMID- 9660788
TI  - The cellular trafficking and zinc dependence of secretory and lysosomal
      sphingomyelinase, two products of the acid sphingomyelinase gene.
AB  - The acid sphingomyelinase (ASM) gene, which has been implicated in ceramide
      mediated cell signaling and atherogenesis, gives rise to both lysosomal SMase (L
      SMase), which is reportedly cation-independent, and secretory SMase (S-SMase),
      which is fully or partially dependent on Zn2+ for enzymatic activity. Herein we
      present evidence for a model to explain how a single mRNA gives rise to two forms
      of SMase with different cellular trafficking and apparent differences in Zn2+
      dependence. First, we show that both S-SMase and L-SMase, which contain several
      highly conserved zinc-binding motifs, are directly activated by zinc. In
      addition, SMase assayed from a lysosome-rich fraction of Chinese hamster ovary
      cells was found to be partially zinc-dependent, suggesting that intact lysosomes
      from these cells contain subsaturating levels of Zn2+. Analysis of Asn-linked
      oligosaccharides and of N-terminal amino acid sequence indicated that S-SMase
      arises by trafficking through the Golgi secretory pathway, not by cellular
      release of L-SMase during trafficking to lysosomes or after delivery to
      lysosomes. Most importantly, when Zn2+-dependent S-SMase was incubated with SMase
      negative cells, the enzyme was internalized, trafficked to lysosomes, and became
      zinc-independent. We conclude that L-SMase is exposed to cellular Zn2+ during
      trafficking to lysosomes, in lysosomes, and/or during cell homogenization. In
      contrast, the pathway targeting S-SMase to secretion appears to be relatively
      sequestered from cellular pools of Zn2+; thus S-SMase requires exogeneous Zn2+
      for full activity. This model provides important information for understanding
      the enzymology and regulation of L- and S-SMase and for exploring possible roles
      of ASM gene products in cell signaling and atherogenesis.

PMID- 9660789
TI  - Distinct mechanisms for K+ efflux, intoxication, and hemolysis by Bordetella
      pertussis AC toxin.
AB  - Adenylate cyclase (AC) toxin from Bordetella pertussis delivers its catalytic
      domain to the interior of target cells where it converts host ATP to cAMP in a
      process referred to as intoxication. This toxin also hemolyzes sheep erythrocytes
      by a mechanism presumed to include pore formation and osmotic lysis. Intoxication
      and hemolysis appear at strikingly different toxin concentrations and evolve over
      different time scales, suggesting that different molecular processes may be
      involved. The present study was designed to test the hypothesis that intoxication
      and hemolysis occur by distinct mechanisms. Although the hemolytic activity of AC
      toxin has a lag of >1 h, intoxication starts immediately. Because of this
      difference, we sought a surrogate or precursor lesion that leads to hemolysis,
      and potassium efflux has been observed from erythrocytes treated with other pore
      forming toxins. AC toxin elicits an increase in K+ efflux from sheep erythrocytes
      and Jurkat cells, a human T-cell leukemia line, that begins within minutes of
      toxin addition. The toxin concentration dependence along with the analysis of the
      time course suggest that toxin monomers are sufficient to elicit release of K+
      and to deliver the catalytic domain to the cell interior. Hemolysis, on the other
      hand, is a highly cooperative event that likely requires a subsequent
      oligomerization of these individual units. Although induction of K+ efflux shares
      some structural and environmental requirements with both intoxication and
      hemolysis, it can occur under conditions in which intoxication is reduced or
      prevented. The data presented here suggest that the transmembrane pathway by
      which K+ is released is separate and distinct from the structure required for
      intoxication but may be related to, or a precursor of, that which is ultimately
      responsible for hemolysis.

PMID- 9660790
TI  - The urokinase-type plasminogen activator receptor mediates tyrosine
      phosphorylation of focal adhesion proteins and activation of mitogen-activated
      protein kinase in cultured endothelial cells.
AB  - Urokinase-type plasminogen activator (uPA) binds to cells via a specific
      glycosylphosphatidylinositol-anchored receptor. Although occupancy of the uPA
      receptor (uPAR) has been shown to alter cellular function and to induce gene
      expression, the signaling mechanism has not been characterized. Urokinase induced
      an increase in the tyrosine phosphorylation of multiple proteins in bovine aortic
      endothelial cells. In contrast, low molecular weight uPA did not induce this
      response. Analysis by immunoblotting demonstrated tyrosine phosphorylation of
      focal adhesion kinase (FAK), the focal adhesion-associated proteins paxillin and
      p130(cas), and mitogen-activated protein kinase (MAPK) following the occupancy of
      the uPAR by uPA. Treatment of cells with phosphatidylinositol-specific
      phospholipase C, which cleaves glycosylphosphatidylinositol-linked proteins from
      the cell surface, blocked the uPA-induced tyrosine phosphorylation of FAK,
      indicating the requirement of an intact uPAR on the cell surface. The uPA-induced
      activation of MAPK was completely inhibited by genistein, but not by 4-amino-5-(4
      methylphenyl)-7-(t-butyl)pyrazolo[3, 4-d]pyrimidine, a specific inhibitor of Src
      family kinases. Thus, this study demonstrates a novel role for the uPAR in
      endothelial cell signal transduction that involves the activation of FAK and
      MAPK, which are mediated by the receptor-binding domain of uPA. This may have
      important implications for the mechanism through which uPA influences cell
      migration and differentiation.

PMID- 9660791
TI  - A new tyrosine-phosphorylated 97-kDa adaptor protein mediates interleukin-2
      induced association of SHP-2 with p85-phosphatidylinositol 3-kinase in human T
      lymphocytes.
AB  - Interleukin (IL)-2 is a major cytokine that controls differentiation and
      proliferation of T lymphocytes. In this report we characterize an as yet
      unidentified 97-kDa protein that is a major tyrosine kinase substrate in IL-2
      stimulated cells. pp97 was found to associate with the p85.p110
      phosphatidylinositol 3-kinase complex, the Src homology 2 (SH2) domain-containing
      tyrosine phosphatase SHP-2, and the adaptor molecules CrkL and Grb2. We
      demonstrate that these interactions are directly mediated through the SH2 domains
      of CrkL, p85, and SHP-2 and through the SH3 domains of Grb2. pp97 was found to
      mediate the IL-2-induced interaction between p85 and both a phosphorylated and a
      non-phosphorylated form of SHP-2. In this study we show that pp97 behaves as a
      docking protein and associates with at least CrkL, p85, and SHP-2 in the same
      multimolecular complex. We thus characterized pp97 as a new tyrosine kinase
      substrate in human T lymphocytes which might play a central role in the
      regulation of several pathways activated by IL-2.

PMID- 9660792
TI  - Differential exposure of surface epitopes in the beta-strand region of LOOP1 of
      the yeast H+-ATPase during catalysis.
AB  - The plasma membrane H+-ATPase of yeast assumes distinct conformational states
      during its catalytic cycle. To better understand structural changes in the LOOP1
      domain, a catalytically important cytoplasmic loop segment linking transmembrane
      segments 2 and 3, surface epitopes were examined at different stages of
      catalysis. A polyclonal rabbit antibody was prepared to a fusion protein
      consisting of LOOP1 and the maltose binding protein. This antibody was affinity
      purified to produce a LOOP1-specific fraction that could be used in competition
      enzyme-linked immunosorbent assays to assess surface exposure of the LOOP1
      epitopes. It was found that in an E1 conformation stabilized with either
      adenosine 5'-(beta,gamma -imino)triphosphate (AMP-PNP) or ADP, less than 10% of
      the LOOP1 epitopes were accessible on native enzyme. However, when the enzyme was
      stabilized in an E2-state with ATP plus vanadate, approximately 40% of the
      surface epitopes on LOOP1 became accessible to antibody. The remaining 60% of the
      LOOP1 epitopes were fully occluded in the native enzyme and never showed surface
      exposure. Enzyme-linked immunosorbent assays utilizing fusion proteins consisting
      of LOOP1 subdomains demonstrated that all of the available epitopes were
      contained in the beta-strand region (Glu-195-- Val-267) of LOOP1. The epitopes
      that were differentially exposed during catalysis were included in regions
      upstream and downstream of the highly conserved TGES sequence. Our results
      suggest that during catalysis either the beta-strand region of LOOP1 or an
      interacting domain undergoes substantial structural rearrangement that
      facilitates epitope exposure.

PMID- 9660793
TI  - Binding and functional properties of recombinant and endogenous CXCR3 chemokine
      receptors.
AB  - IP10 and MIG are two members of the CXC branch of the chemokine superfamily whose
      expression is dramatically up-regulated by interferon (IFN)-gamma. The proteins
      act largely on natural killer (NK)-cells and activated T-cells and have been
      implicated in mediating some of the effects of IFN-gamma and lipopolysaccharides
      (LPSs), as well as T-cell-dependent anti-tumor responses. Recently both
      chemokines have been shown to be functional agonists of the same G-protein
      coupled receptor, CXCR3. We now report the pharmacological characterization of
      CXCR3 and find that, when heterologously expressed, CXCR3 binds IP10 and MIG with
      Ki values of 0.14 and 4.9 nM, respectively. The receptor has very modest affinity
      for SDF-1alpha and little or no affinity for other CXC-chemokines. The properties
      of the endogenous receptor expressed on activated T-cells are similar.
      Surprisingly, several CC-chemokines, particularly eotaxin and MCP-4, also compete
      with moderate affinity for the binding of IP10 to CXCR3. Eotaxin does not
      activate CXCR3 but, in CXCR3-transfected cells, can block IP10-mediated receptor
      activation. Eotaxin, therefore, may be a natural CXCR3 antagonist.

PMID- 9660794
TI  - Characterization of the interactions of plasminogen and tissue and vampire bat
      plasminogen activators with fibrinogen, fibrin, and the complex of D-dimer
      noncovalently linked to fragment E.
AB  - Vampire bat plasminogen activator (b-PA) causes less fibrinogen (Fg) consumption
      than tissue-type plasminogen activator (t-PA). Herein, we demonstrate that this
      occurs because the complex of D-dimer noncovalently linked to fragment E ((DD)E),
      the most abundant degradation product of cross-linked fibrin, as well as Fg,
      stimulate plasminogen (Pg) activation by t-PA more than b-PA. To explain these
      findings, we characterized the interactions of t-PA, b-PA, Lys-Pg, and Glu-Pg
      with Fg and (DD)E using right angle light scattering spectroscopy. In addition,
      interactions with fibrin were determined by clotting Fg in the presence of
      various amounts of t-PA, b-PA, Lys-Pg, or Glu-Pg and quantifying unbound material
      in the supernatant after centrifugation. Glu-Pg and Lys-Pg bind fibrin with Kd
      values of 13 and 0.13 microM, respectively. t-PA binds fibrin through two classes
      of sites with Kd values of 0.05 and 2.6 microM, respectively. The second kringle
      (K2) of t-PA mediates the low affinity binding that is eliminated with epsilon
      amino-n-caproic acid. In contrast, b-PA binds fibrin through a single kringle
      independent site with a Kd of 0.15 microM. t-PA competes with b-PA for fibrin
      binding, indicating that both activators share the same finger-dependent site on
      fibrin. Glu-Pg binds (DD)E with a Kd of 5.4 microM. Lys-Pg binds to (DD)E and Fg
      with Kd values of 0.03 and 0.23 microM, respectively. t-PA binds to (DD)E and Fg
      with Kd values of 0.02 and 0.76 microM, respectively; interactions were
      eliminated with epsilon-amino-n-caproic acid, consistent with K2-dependent
      binding. Because it lacks a K2-domain, b-PA does not bind to either (DD)E or Fg,
      thereby explaining why b-PA is more fibrin-specific than t-PA.

PMID- 9660795
TI  - An initiation zone of chromosomal DNA replication at the chicken lysozyme gene
      locus.
AB  - The chicken lysozyme gene domain is distinguished by a broad knowledge of how its
      expression is regulated. Here, we examined the in vivo replication of the
      lysozyme gene locus using polymerase chain reaction amplification and competitive
      polymerase chain reaction of size-fractionated, nascent DNA strands. We found
      that DNA replication initiates at multiple sites within a broad initiation zone
      spanning at least 20 kilobases, which includes most of the lysozyme gene domain.
      The 5' border of this zone is probably located downstream of the lysozyme 5'
      nuclear matrix attachment region. Preferred initiation occurs in a 3'-located
      subzone. The initiation zone at the lysozyme gene locus is also active in
      nonexpressing liver DU249 cells. Furthermore, examining the timing of DNA
      replication at the lysozyme gene locus revealed that the gene locus replicates
      early during S phase in both HD11 and DU249 cells, irrespective of its
      transcriptional activity.

PMID- 9660796
TI  - Promotion and inhibition of L-type Ca2+ channel facilitation by distinct domains
      of the subunit.
AB  - Ca2+ current potentiation by conditioning depolarization is a general mechanism
      by which excitable cells can control the level of Ca2+ entry during repetitive
      depolarizations. Several types of Ca2+ channels are sensitive to conditioning
      depolarization, however, using clearly distinguishable mechanisms. In the case of
      L-type Ca2+ channels, prepulse-induced current facilitation can only be recorded
      when the pore-forming alpha1C subunit is coexpressed with the auxiliary beta1,
      beta3, or beta4, but not beta2, subunit. These four beta subunits are composed of
      two conserved domains surrounded by central, N-terminal, and C-terminal variable
      regions. Using different deleted and chimeric forms of the beta1 and beta2
      subunits, we have mapped essential sequences for L-type Ca2+ channel
      facilitation. A first sequence, located in the second conserved domain of all
      beta subunits, is responsible for the promotion of current facilitation by the
      beta subunit. A second sequence of 16 amino acids, located on the N-terminal tail
      of the beta2 subunit, induces a transferable block of L-type current
      facilitation. Site-specific mutations reveal the essential inhibitory role played
      by three positive charges on this segment. The lack of prepulse-induced current
      facilitation recorded with some truncated forms of the beta2 subunit suggests the
      existence of an additional inhibitory sequence in the beta2 subunit.

PMID- 9660797
TI  - Mutation of individual serine residues in the C-terminal tail of the
      lutropin/choriogonadotropin receptor reveal distinct structural requirements for
      agonist-induced uncoupling and agonist-induced internalization.
AB  - We have previously mapped the agonist-induced phosphorylation of the rat
      lutropin/choriogonadotropin receptor (rLHR) to a locus of four serines (Ser635,
      Ser639, Ser649, and Ser652) located in the C-terminal tail. The removal or
      mutation of this locus delays the time course of agonist-induced uncoupling of
      the rLHR from its effector system without affecting the overall magnitude of
      uncoupling, and it retards the endocytosis of the agonist-receptor complex. We
      have now prepared and analyzed four new rLHR mutants in which each of these
      serines were individually mutated to alanines. The data presented show that each
      mutation reduces agonist-promoted rLHR phosphorylation by 20-40%. Mutation of
      Ser635 or Ser639 delayed the time course of agonist-induced uncoupling to about
      the same extent as the simultaneous mutation of all four serines. Mutation of
      Ser635 or Ser639 also retarded agonist-induced internalization, but the magnitude
      of this decrease was less than that induced by the simultaneous mutation of all
      four serines. Mutation of Ser649 had no effect on agonist-induced uncoupling but
      retarded agonist-induced internalization to the same extent as the simultaneous
      mutation of all four serines. Mutation of Ser652 has little or no effect on
      either of these two parameters. Co-transfection studies with dominant-negative
      arrestins and dominant-negative dynamin reveal that, despite differences in their
      rates of internalization, rLHR-wild-type, rLHR-S639A, and rLHR-S649A are
      internalized by an arrestin- and dynamin-dependent pathway. These data show that
      the structural requirements needed for the agonist-induced uncoupling and
      internalization of the rLHR are distinct.

PMID- 9660798
TI  - Cain, a novel physiologic protein inhibitor of calcineurin.
AB  - Calcineurin is a widely distributed protein phosphatase regulated by calcium and
      calmodulin. It mediates the immunosuppressive actions of drugs such as
      cyclosporin and FK506, and has been implicated in a number of calcium-sensitive
      pathways in the nervous system, including regulation of neurotransmitter release
      and modulation of long-term changes in synaptic plasticity. Calcineurin
      associates physiologically with other proteins, including calmodulin, FKBP12
      (FK506-binding protein), the ryanodine receptor, and the inositol 1,4,5
      trisphosphate receptor. We now report the identification, molecular cloning, and
      functional characterization of a novel protein, cain (calcineurin inhibitor),
      that interacts with and inhibits calcineurin. The full-length cain cDNA predicts
      a 240-kDa protein with no significant homology to any known protein. Cain
      associates with calcineurin both in vitro and in vivo, leading to a non
      competitive inhibition of calcineurin activity. The putative calcineurin-binding
      domain of cain, a 38-amino acid region defined by mutational analysis, is highly
      basic. Like calcineurin, cain has a prominent neuronal expression and a wide
      tissue distribution. Cain's expression pattern in the brain closely resembles
      that of calcineurin, indicating a physiologic association between the two
      proteins.

PMID- 9660799
TI  - A human homologue of the Schizosaccharomyces pombe rad1+ checkpoint gene encodes
      an exonuclease.
AB  - In the fission yeast Schizosaccharomyces pombe the rad1(+) gene is required for
      both the DNA damage-dependent and the DNA replication-dependent cell cycle
      checkpoints. We have identified a human homologue of the S. pombe rad1(+) gene,
      designated Hrad1, as well as a mouse homologue: Mrad1. Two Hrad1 alternative
      splice variants with different open reading frames have been identified; one
      codes for a long form, Hrad1A, and the other encodes a short form because of N
      terminal truncation, Hrad1B. Hrad1A has 60% identity to the S. pombe rad1+
      sequence at the DNA level and 49% identity and 72% similarity at the amino acid
      level. Northern blot analysis indicates elevated levels of expression in testis
      and cancer cell lines. Chromosomal localization by fluorescence in situ
      hybridization indicates that Hrad1 is located on chromosome 5p13. 2-13.3. This
      region is subject to loss of heterozygosity in several human cancers. Hrad1 also
      shares homology with the Saccharomyces cerevisiae RAD17 and Ustilago maydis REC1
      proteins. REC1 has previously been characterized as a 3' --> 5' exonuclease with
      a C-terminal domain essential for cell cycle checkpoint function. We have
      expressed and purified polyhistidine-tagged fusions of Hrad1A and Hrad1B and show
      that HisHrad1A has 3' --> 5' exonuclease activity, whereas HisHrad1B lacks such
      activity. The biological functions of the two proteins remain to be determined.

PMID- 9660800
TI  - Identification of a human homologue of the Schizosaccharomyces pombe rad17+
      checkpoint gene.
AB  - In the fission yeast Schizosaccharomyces pombe the rad17+ gene is required for
      both the DNA damage-dependent and the DNA replication-dependent cell cycle
      checkpoints. We have identified a human cDNA homologue of the S. pombe rad17+
      checkpoint gene, designated Hrad17. Hrad17 has 49% identity to the S. pombe
      rad17+ sequence at the DNA level and 49% identity and 72% similarity at the amino
      acid level. Northern blot analysis indicates elevated levels of expression in
      testis and in cancer cell lines. Chromosomal localization by fluorescence in situ
      hybridization indicates that Hrad17 is located on chromosome 4q13.3-21.2. This
      region is subject to loss of heterozygosity in several human cancers. To begin to
      understand the protein-protein interactions of the human checkpoint machinery, we
      have used the yeast two-hybrid system to examine potential interactions between
      Hrad1, Hrad9, and Hrad17. We demonstrate a physical interaction between Hrad17
      and Hrad1 but no interaction with Hrad9.

PMID- 9660801
TI  - Insulin-like growth factor-binding protein (IGFBP)-3 and IGFBP-5 share a common
      nuclear transport pathway in T47D human breast carcinoma cells.
AB  - Insulin-like growth factor-binding proteins (IGFBPs) play an integral role in
      modifying insulin-like growth factor actions in a wide variety of cell types.
      Recent evidence suggests that IGFBP-3 and IGFBP-5 also have effects on cell
      growth that are insulin-like growth factor-independent. In investigating possible
      mechanisms for this effect, the intracellular trafficking of IGFBP-3 and IGFBP-5,
      both of which contain sequences with the potential for nuclear localization, was
      studied in T47D cells. Nuclear uptake of fluorescently labeled IGFBP-3 and IGFBP
      5 was observed in a proportion of T47D cells that appeared to be rapidly
      dividing. IGFBP-1 and IGFBP-2, which do not possess the putative domain for
      nuclear translocation, were not transported to the nuclei of T47D cells. When
      T47D cells were preincubated with excess unlabeled IGFBP-3, nuclear localization
      of labeled IGFBP-3 or IGFBP-5 was not detected, indicating that their nuclear
      translocation involves a common pathway. Inhibition of receptor-mediated
      endocytosis did not affect nuclear uptake of IGFBP-3, suggesting that it uses an
      alternative non-classical import pathway for transport across the plasma
      membrane. In addition, a variant form of IGFBP-3 with a mutation in the putative
      nuclear localization sequence was unable to translocate to the nuclei of T47D
      cells, suggesting that nuclear translocation of IGFBP-3 was dependent on these
      carboxyl-terminal basic residues.

PMID- 9660802
TI  - Thermodynamics and molecular simulation analysis of hydrophobic substrate
      recognition by aminotransferases.
AB  - Aromatic amino acid aminotransferase (AroAT) and aspartate aminotransferase
      (AspAT) are known as dual-substrate enzymes, which can bind acidic and
      hydrophobic substrates in the same pocket (Kawaguchi, S., Nobe, Y., Yasuoka, J.,
      Wakamiya, T., Kusumoto, S., and Kuramitsu, S. (1997) J. Biochem. (Tokyo) 122, 55
      63). In order to elucidate the mechanism of hydrophobic substrate recognition,
      kinetic and thermodynamic analyses using substrates with different
      hydrophobicities were performed. They revealed that 1) amino acid substrate
      specificity (kmax/Kd) depended on the affinity for the substrate (1/Kd) and 2)
      binding of the hydrophobic side chain was enthalpy-driven, suggesting that van
      der Waals interactions between the substrate-binding pocket and hydrophobic
      substrate predominated. Three-dimensional structures of AspAT and AroAT bound to
      alpha-aminoheptanoic acid were built using the homology modeling method. A
      molecular dynamic simulation study suggested that the outward-facing position of
      the Arg292 side chain was the preferred state to a greater extent in AroAT than
      AspAT, which would make the hydrophobic substrate bound state of the former more
      stable. Furthermore, AroAT appeared to have a more flexible conformation than
      AspAT. Such flexibility would be expected to reduce the energetic cost of
      conformational rearrangement induced by substrate binding. These two mechanisms
      (positional preference of Arg and flexible conformation) may account for the high
      activity of AroAT toward hydrophobic substrates.

PMID- 9660803
TI  - Altered cell surface expression and signaling of leptin receptors containing the
      fatty mutation.
AB  - Leptin and the leptin receptor are key players in the regulation of body weight.
      In an attempt to dissect the molecular mechanism of the Zucker fatty rat leptin
      receptor mutation (Gln269 --> Pro) we analyzed the effects of this mutation on
      leptin receptor signaling and expression in three different expression systems:
      1) 32D cells expressing leptin/erythropoietin receptor chimeras, 2) COS-7 cells
      expressing a leptin receptor short form, and 3) 293 cells expressing soluble
      receptor forms. To determine if the Gln269 --> Pro mutation is critical for the
      observed phenotype, we made a similar Gln --> Pro mutation at a vicinal residue
      two amino acids upstream of the fatty mutation to see if it would have similar
      effects. Incorporation of either of the Gln --> Pro mutations into wild type
      receptor forms did not interfere with leptin binding, but it resulted in a
      signaling-incompetent receptor. In addition, the majority of the mutant receptor
      protein was localized intracellularly. Our results suggest that the obese
      phenotype resulting from the Gln269 --> Pro mutation in the leptin receptor of
      the Zucker fatty rat may be due not only to a reduced cell surface expression of
      this form of the leptin receptor, but also to a post-leptin binding malfunction
      of the receptor that interferes with subsequent signal transduction.

PMID- 9660804
TI  - Improved potency of hyperactive and actin-resistant human DNase I variants for
      treatment of cystic fibrosis and systemic lupus erythematosus.
AB  - The ability of recombinant human DNase I (DNase I) to degrade DNA to lower
      molecular weight fragments is the basis for its therapeutic use in cystic
      fibrosis (CF) patients and its potential use as a treatment for systemic lupus
      erythematosus (SLE). To increase the potency of human DNase I, we have generated
      and characterized three classes of mutants: (a) hyperactive variants, which have
      from one to six additional positively charged residues (+1 to +6) and digest DNA
      much more efficiently relative to wild type, (b) actin-resistant variants, which
      are no longer inhibited by G-actin, a potent inhibitor of DNase I, and (c)
      combination variants that are both hyperactive and actin-resistant. For DNA
      scission in CF sputum where the DNA concentration and length are large, we
      measured a approximately 20-fold increase in potency relative to wild type for
      the +3 hyperactive variant Q9R/E13R/N74K or the actin-resistant variant A114F;
      the hyperactive and actin-resistant combination variant was approximately 100
      fold more potent than wild type DNase I. For digesting lower concentrations of
      DNA complexed to anti-DNA antibodies in human serum, we found a maximal
      enhancement of approximately 400-fold over wild type for the +2 variant
      E13R/N74K. The +3 enzymes have approximately 4000-fold enhancement for degrading
      moderate levels of exogenous DNA spiked into human serum, whereas the +6 enzyme
      has approximately 30,000-fold increased activity for digesting the extremely low
      levels of endogenous DNA found in serum. The actin resistance property of the
      combination mutants further enhances the degree of potency in human serum. Thus,
      the human DNase I variants we have engineered for improved biochemical and
      pharmacodynamic properties have greater therapeutic potential for treatment of
      both CF and SLE.

PMID- 9660805
TI  - In vivo transcription of nrdAB operon and of grxA and fpg genes is triggered in
      Escherichia coli lacking both thioredoxin and glutaredoxin 1 or thioredoxin and
      glutathione, respectively.
AB  - We have previously described () that Escherichia coli maintains a balanced supply
      of deoxyribonucleotides by a regulatory mechanism that up-regulates the levels of
      ribonucleotide reductase with the lack of its main hydrogen donors thioredoxin,
      glutaredoxin 1, and glutathione (GSH). By using a semi-quantitative reverse
      transcription/multiplex polymerase chain reaction fluorescent procedure that
      enables simultaneous analysis of up to seven mRNA species, we now demonstrate
      that regulation operates at the transcriptional level. Double mutant cells
      lacking both thioredoxin and glutaredoxin 1 had increased transcription of the
      nrdAB operon, as compared with the corresponding wild type parent (maximal
      induction of 10- and 9-fold for mRNA of nrdA and nrdB genes, respectively).
      Likewise, a dramatic increase of 36-fold in grxA mRNA was observed in bacteria
      simultaneously deficient in thioredoxin and GSH (the physiological reductant of
      all glutaredoxins). The increased expression of the grxA gene in trxA gshA double
      mutant bacteria was mimicked in trxA single mutant cells by depletion of GSH with
      diethylmaleate (DEM). This induction of grxA transcription was rapid since
      maximal increase was detected upon 10 min of DEM exposure. Like grxA expression,
      the basal level of fpg mRNA, encoding formamidopyrimidine-DNA glycosylase, was
      increased (about 4-fold) in a trxA gshA double mutant strain; this expression was
      also induced upon exposure to DEM (11-fold maximal induction). These results
      suggest that transcription of grxA might share common redox regulatory
      mechanism(s) with that of the fpg gene, involved in the repair of 8-oxoguanine in
      DNA.

PMID- 9660806
TI  - Mt-Hsp70 homolog, Ssc2p, required for maturation of yeast frataxin and
      mitochondrial iron homeostasis.
AB  - Here we show that the yeast mitochondrial chaperone Ssc2p, a homolog of mt-Hsp70,
      plays a critical role in mitochondrial iron homeostasis. Yeast with ssc2-1
      mutations were identified by a screen for altered iron-dependent gene regulation
      and mitochondrial dysfunction. These mutants exhibit increased cellular iron
      uptake, and the iron accumulates exclusively within mitochondria. Yfh1p is
      homologous to frataxin, the human protein implicated in the neurodegenerative
      disease, Friedreich's ataxia. Like mutants of yfh1, ssc2-1 mutants accumulate
      vast quantities of iron in mitochondria. Furthermore, using import studies with
      isolated mitochondria, we demonstrate a specific role for Ssc2p in the maturation
      of Yfh1p within this organelle. This function for a mitochondrial Hsp70 chaperone
      is likely to be conserved, implying that a human homolog of Ssc2p may be involved
      in iron homeostasis and in neurodegenerative disease.

PMID- 9660807
TI  - Neuronal nicotinic receptors in the locust Locusta migratoria. Cloning and
      expression.
AB  - We have identified five cDNA clones that encode nicotinic acetylcholine receptor
      (nAChR) subunits expressed in the nervous system of the locust Locusta
      migratoria. Four of the subunits are ligand-binding alpha subunits, and the other
      is a structural beta subunit. The existence of at least one more nAChR gene,
      probably encoding a beta subunit, is indicated. Based on Northern analysis and in
      situ hybridization, the five subunit genes are expressed. localpha1, localpha3,
      and locbeta1 are the most abundant subunits and are expressed in similar areas of
      the head ganglia and retina of the adult locust. Because Loc<alpha3 binds alpha
      bungarotoxin with high affinity, it may form a homomeric nAChR subtype such as
      the mammalian alpha7 nAChR. Localpha1 and Locbeta1 may then form the predominant
      heteromeric nAChR in the locust brain. localpha4 is mainly expressed in optic
      lobe ganglionic cells and localpha2 in peripherally located somata of mushroom
      body neurons. localpha3 mRNA was additionally detected in cells interspersed in
      the somatogastric epithelium of the locust embryo, suggesting that this isoform
      may also be involved in functions other than neuronal excitability. Transcription
      of all nAChR subunit genes begins approximately 3 days before hatching and
      continues throughout adult life. Electrophysiological recordings from head
      ganglionic neurons also indicate the existence of more than one functionally
      distinct nAChR subtype. Our results suggest the existence of several nAChR
      subtypes, at least some of them heteromeric, in this insect species.

PMID- 9660808
TI  - Expression of GTPase-deficient Gialpha2 results in translocation of cytoplasmic
      RGS4 to the plasma membrane.
AB  - The members of a recently identified protein family termed regulators of G
      protein signaling (RGS) act as GTPase-activating proteins for certain Galpha
      subunits in vitro, but their physiological effects in cells are uncertain in the
      face of similar biochemical activity and overlapping patterns of tissue
      expression. Consistent with its activity in in vitro GTPase-activating protein
      assays, RGS4 interacts efficiently with endogenous proteins of the Gi and Gq
      subclasses of Galpha subunits but not with G12alpha or Gsalpha. Unlike other RGS
      proteins such as RGS9, RGS-GAIP, and Sst2p, which have been reported to be
      largely membrane-associated, a majority of cellular RGS4 is found as a soluble
      protein in the cytoplasm. However, the expression of a GTPase-deficient Gialpha
      subunit (Gialpha2-Q204L) resulted in the translocation of both wild type RGS4 and
      a non-Gialpha-binding mutant (L159F) to the plasma membrane. These data suggest
      that RGS4 may be recruited to the plasma membrane indirectly by G-protein
      activation and that multiple RGS proteins within a given cell might be
      differentially localized to determine a physiologic response to a G-protein
      linked stimulus.

PMID- 9660809
TI  - Replacement of tyrosine 1251 in the carboxyl terminus of the insulin-like growth
      factor-I receptor disrupts the actin cytoskeleton and inhibits proliferation and
      anchorage-independent growth.
AB  - Insulin-like growth factor (IGF)-I signaling through the IGF-I receptor modulates
      cellular adhesion and proliferation and the transforming ability of cells
      overexpressing the IGF-I receptor. Tyrosine phosphorylation of intracellular
      proteins is essential for this transduction of the IGF-I-induced mitogenic and
      tumorigenic signals. IGF-I induces specific cytoskeletal structure and the
      phosphorylation of proteins in the associated focal adhesion complexes. The
      determination of the exact pathways emanating from the IGF-I receptor that are
      involved in mediating these signals will contribute greatly to the understanding
      of IGF-I action. We have previously shown that replacement of tyrosine residues
      1250 and 1251 in the carboxyl terminus of the IGF-I receptor abrogates IGF-I
      induced cellular proliferation and tumor formation in nude mice. In this study,
      replacement of either tyrosine 1250 or 1251 similarly reduces the cells ability
      to grow in an anchorage-independent manner. The actin cytoskeleton and cellular
      localization of vinculin are disrupted by replacement of tyrosine 1251. Tyrosine
      residues 1250 and 1251 are not essential for tyrosine phosphorylation of two
      known substrates; insulin receptor substrate-1 and SHC, nor association of known
      downstream adaptor proteins to these substrates. In addition, these mutant IGF-I
      receptors do not affect IGF-I-stimulated p42/p44 mitogen-activated protein kinase
      activation or phosphatidylinositol (PI) 3'-kinase activity. Thus, it appears that
      in fibroblasts expressing tyrosine 1250 and 1251 mutant IGF-I receptors, the
      signal transduction pathways impacting on mitogenesis and tumorigenesis do not
      occur exclusively through the PI 3'-kinase or mitogen-activated protein kinase
      pathways.

PMID- 9660810
TI  - The light chain-binding domain of the smooth muscle myosin heavy chain is not the
      only determinant of regulation.
AB  - Interactions between the dephosphorylated regulatory light chains (RLCs) of
      smooth muscle myosin are involved in maintaining the enzymatically "off" state.
      Expressed chimeric smooth muscle heavy meromyosins containing skeletal muscle
      myosin heavy chain (HC) sequences were used to assess the relative importance of
      the light chain-binding domain (or "neck") to regulation. Surprisingly,
      regulation remained intact with a skeletal RLC-binding site. A chimera with the
      entire alpha-helical neck composed of skeletal HC sequence showed 2-fold
      regulation of motility and nearly 5-fold regulation of actin-activated ATPase
      activity. Complete activation of the dephosphorylated state (i.e. complete loss
      of regulation) occurred when skeletal HC sequence extended from the head/rod
      junction to the SH1-SH2 helix. Smooth muscle-specific sequences near the motor
      domain may therefore position the regulatory domain in a way that optimizes RLC
      rod-head interactions, thus enabling a completely off state when the RLC is
      dephosphorylated. Conversely, a chimera that joins the motor domain from
      unconventional myosin V to the smooth muscle myosin neck and rod showed only 2
      fold regulation. The presence of the smooth muscle light chain-binding region and
      rod is therefore not sufficient to confer complete phosphorylation-dependent
      regulation upon all motor domains of the myosin family.

PMID- 9660811
TI  - Cryoelectron microscopy and image analysis of the cardiac ryanodine receptor.
AB  - The three-dimensional structure of the cardiac muscle ryanodine receptor (RyR2)
      is described and compared with its skeletal muscle isoform (RyR1). Previously,
      structural studies of RyR2 have not been as informative as those for RyR1 because
      optimal conditions for electron microscopy, which require low levels of
      phospholipid, are destabilizing for RyR2. A simple procedure was devised for
      diluting RyR2 (in phospholipid-containing buffer) into a lipid-free buffer
      directly on the electron microscope grid, followed by freezing within a few
      seconds. Cryoelectron microscopy of RyR2 so prepared yielded images of sufficient
      quality for analysis by single particle image processing. Averaged projection
      images for RyR2, as well as for RyR1, prepared under the same conditions, were
      found to be nearly identical in overall dimensions and appearance at the
      resolution attained, approximately 30 A. An initial three-dimensional
      reconstruction of RyR2 was determined (resolution approximately 41 A) and
      compared with previously reported reconstructions of RyR1. Although they looked
      similar, which is consistent with the similarity found for the projection images,
      and with expectations based on the 66% amino acid sequence identity of the two
      isoforms, structural differences near the corners of the cytoplasmic assembly
      were observed in both two- and three-dimensional studies.

PMID- 9660812
TI  - Identification of amino acid residues in a class I ubiquitin-conjugating enzyme
      involved in determining specificity of conjugation of ubiquitin to proteins.
AB  - The ubiquitin pathway is a major system for selective proteolysis in eukaryotes.
      However, the mechanisms underlying substrate selectivity by the ubiquitin system
      remain unclear. We previously identified isoforms of a rat ubiquitin-conjugating
      enzyme (E2) homologous to the Saccharomyces cerevisiae class I E2 genes,
      UBC4/UBC5. Two isoforms, although 93% identical, show distinct features. UBC4-1
      is expressed ubiquitously, whereas UBC4-testis is expressed in spermatids.
      Interestingly, although these isoforms interacted similarly with some ubiquitin
      protein ligases (E3s) such as E6-AP and rat p100 and an E3 that conjugates
      ubiquitin to histone H2A, they also supported conjugation of ubiquitin to
      distinct subsets of testis proteins. UBC4-1 showed an 11-fold greater ability to
      support conjugation of ubiquitin to endogenous substrates present in a testis
      nuclear fraction. Site-directed mutagenesis of the UBC4-testis isoform was
      undertaken to identify regions of the molecule responsible for the observed
      difference in substrate specificity. Four residues (Gln-15, Ala-49, Ser-107, and
      Gln-125) scattered on surfaces away from the active site appeared necessary and
      sufficient for UBC4-1-like conjugation. These four residues identify a large
      surface of the E2 core domain that may represent an area of binding to E3s or
      substrates. These findings demonstrate that a limited number of amino acid
      substitutions in E2s can dictate conjugation of ubiquitin to different proteins
      and indicate a mechanism by which small E2 molecules can encode a wide range of
      substrate specificities.

PMID- 9660813
TI  - Post-translational processing of the insulin-like growth factor-2 precursor.
      Analysis of O-glycosylation and endoproteolysis.
AB  - Insulin-like growth factor-2 (IGF-2) is expressed in most embryonic tissues and
      is required for normal development during gestation. After birth IGF-2 expression
      is extinguished in most tissues, but the gene is often reactivated during
      tumorigenesis. Tumors secrete high molecular weight forms of IGF-2 that result
      from aberrant post-translational processing of pro-IGF-2. As a first step toward
      understanding how high molecular weight IGF-2 peptides might contribute to tumor
      progression, we have characterized the biosynthesis of IGF-2 in a human embryonic
      cell line. We have found that pro-IGF-2 can initially form two disulfide isomers
      that undergo rearrangement to a single conformation in vivo. The addition of N
      acetylgalactosamine to Ser71, Thr72, Thr75, and Thr139 likely occurs in the cis-
      Golgi apparatus. Sialic acid addition begins in the trans- Golgi apparatus, but
      IGF-2 peptides must reach the trans-Golgi network for oligosaccharide maturation
      to be completed. Endoproteolysis occurs concomitant to or slightly after
      oligosaccharide maturation. Cleavage was observed only at Arg104, resulting in
      the secretion of IGF-2-(1-104) and free E-peptide. Proteolysis required basic
      residues in the P1 (Arg104) and P4 (Arg101) positions, was completely blocked by
      a furin inhibitor, and was enhanced by coexpression with furin, PACE4, PC6A,
      PC6B, and LPC. These data suggest that members of the subtilisin-related
      proprotein convertase family mediate processing of pro-IGF-2 at Arg104. We did
      not detect the IGF-2 peptides that are most abundant in normal serum, mature IGF
      2, and IGF-2-(1-87), in this expression system, which indicates that novel
      endoproteases are responsible for generating these products.

PMID- 9660814
TI  - The carboxyl-terminal region of EBP50 binds to a site in the amino-terminal
      domain of ezrin that is masked in the dormant molecule.
AB  - EBP50 (ezrin-radixin-moesin-binding phosphoprotein 50) was recently identified by
      affinity chromatography on the immobilized NH2-terminal domain of ezrin. Here we
      map and characterize the regions in EBP50 and ezrin necessary for this
      association. Using blot overlays and in solution binding assays, the COOH
      terminal 30 residues of EBP50 were found to be sufficient for an association with
      residues 1-286 of ezrin. EBP50 did not bind to full-length (1-585) ezrin,
      indicating that the EBP50 binding site is masked in the full-length molecule.
      Ezrin contains two complementary self-association domains known as N- and C
      ERMADs (ezrin-radixin-moesin-association domains), encompassing residues 1-296
      and 479-585, respectively. An ezrin 1-583 construct lacking the two terminal
      residues necessary for this association was found to have an unmasked EBP50
      binding site. Moreover, binding of EBP50 and the C-ERMAD to ezrin residues 1-296
      was found to be mutually exclusive, with the C-ERMAD having a higher affinity.
      These results suggest that in full-length ezrin, the binding site for EBP50 is
      masked through an intramolecular N/C-ERMAD association. Based on these and
      additional results, we propose a model whereby dormant ezrin can be activated to
      bind EBP50 on its NH2-terminal end and F-actin on its COOH-terminal end. Since
      EBP50 is proposed to bind membrane proteins through its PDZ domains, this
      provides a molecular description of the regulated linkage of microfilaments to
      membranes in cell surface microvilli.

PMID- 9660815
TI  - Identification and characterization of a new latent transforming growth factor
      beta-binding protein, LTBP-4.
AB  - Transforming growth factor betas (TGF-betas) are secreted by most cell types as
      latent high molecular weight complexes consisting of TGF-beta and its latency
      associated peptide (LAP) propeptide dimers, covalently linked to latent TGF-beta
      binding proteins (LTBPs). Currently, three different LTBPs are known (LTBPs 1, 2,
      and 3), all with highly similar protein domain structure consisting of epidermal
      growth factor-like and 8-Cys repeats. The 3rd 8-Cys repeat of LTBP-1 mediates its
      association with TGF-beta1.LAP. By using an expressed sequence tag homologous to
      the 3rd 8-Cys repeat of human LTBP-1 as a probe, a novel cDNA similar to known
      LTBPs was cloned from human heart cDNA library. This cDNA was named LTBP-4 and
      found to exist in at least four different forms, generated by alternative
      splicing at the amino terminus and at the central epidermal growth factor repeat
      domain. One of the alternative amino-terminal forms contained an RGD sequence,
      indicating possible cell-surface interactions with integrins. LTBP-4 gene was
      localized to chromosomal position 19q13. 1-19q13.2. The major LTBP-4 mRNA form is
      about 5.1 kilobase pairs in size and is predominantly expressed in the heart,
      aorta, uterus, and small intestine. Immunoblotting analysis indicated that LTBP-4
      was secreted from cultured human lung fibroblasts both in a free form and in a
      disulfide bound complex with a TGF-beta. LAP-like protein. Both LTBP-4 forms were
      also found to be deposited in the extracellular matrix. The matrix-associated
      LTBP-4 was susceptible to proteolytic release with plasmin. LTBP-4 is a new
      member of the growing LTBP-fibrillin family of proteins and offers an alternative
      means for the secretion and targeted matrix deposition of TGF-betas or related
      proteins.

PMID- 9660816
TI  - Characterization of a temperature-sensitive yeast vacuolar ATPase mutant with
      defects in actin distribution and bud morphology.
AB  - The 27-kDa E subunit, encoded by the VMA4 gene, is a peripheral membrane subunit
      of the yeast vacuolar H+-ATPase. We have randomly mutagenized the VMA4 gene in
      order to examine the structure and function of the 27-kDa subunit. Cells lacking
      a functional VMA4 gene are unable to grow at pH > 7 or in elevated concentrations
      of CaCl2. Plasmid-borne, mutagenized vma4 genes were screened for failure to
      complement these phenotypes. Mutants producing Vma4 proteins detectable by
      immunoblot were selected; one (vma4-1(ts)) is temperature conditional, exhibiting
      the Vma- phenotype only at elevated temperature (37 degreesC). Sequencing
      revealed that a single point mutation, D145G, was responsible for the phenotypes
      of the vma4-1(ts) allele. The unassembled 27-kDa subunit made in the vma4-1(ts)
      cells is rapidly degraded, particularly at 37 degreesC, but can be protected from
      degradation by prior assembly into the V-ATPase complex. In purified vacuolar
      vesicles from the mutant cells, the peripheral subunits are localized to the
      vacuolar membrane at decreased levels and a comparably decreased level of ATPase
      activity (14% of the activity in wild-type vesicles) is observed. When vma4-1(ts)
      mutant cells are shifted to pH 7.5 medium at 37 degrees C, the cells become
      enlarged and exhibit multiple large buds, elongated buds, and other abnormal
      morphologies, together with delocalization of actin and chitin, within 4 h. These
      phenotypes suggest connections between the vacuolar ATPase, bud morphology, and
      cytokinesis that had not been recognized previously.

PMID- 9660817
TI  - Cloning and characterization of shk2, a gene encoding a novel p21-activated
      protein kinase from fission yeast.
AB  - We describe the characterization of a novel gene, shk2, encoding a second
      p21(cdc42/rac)-activated protein kinase (PAK) homolog in fission yeast. Like
      other known PAKs, Shk2 binds to Cdc42 in vivo and in vitro. While overexpression
      of either shk2 or cdc42 alone does not impair growth of wild type fission yeast
      cells, cooverexpression of the two genes is toxic and leads to highly aberrant
      cell morphology, providing evidence for functional interaction between Cdc42 and
      Shk2 proteins in vivo. Fission yeast shk2 null mutants are viable and exhibit no
      obvious phenotypic defects. Overexpression of shk2 restores viability and normal
      morphology but not full mating competence to fission yeast cells carrying a shk1
      null mutation. Additional genetic data suggest that Shk2, like Cdc42 and Shk1,
      participates in Ras-dependent morphological control and mating response pathways
      in fission yeast. We also show that overexpression of byr2, a gene encoding a
      Ste11/MAPK kinase kinase homolog, suppresses the mating defect of cells partially
      defective for Shk1 function, providing evidence of a link between PAKs and
      mitogen-activated protein kinase signaling in fission yeast. Taken together, our
      results suggest that Shk2 is partially overlapping in function with Shk1, with
      Shk1 being the dominant protein in function.

PMID- 9660819
TI  - Gene-specific transcriptional activity of the insulin cAMP-responsive element is
      conferred by NF-Y in combination with cAMP response element-binding protein.
AB  - Cyclic AMP stimulates insulin gene transcription through a cAMP response element
      (CRE). In the present study the insulin CRE-binding proteins and their functions
      were investigated. A mutational analysis of nuclear protein binding in
      electrophoretic mobility shift assays in combination with specific antisera
      showed that in the CRE of the rat insulin I gene the imperfect CRE octamer-like
      sequence TGACGTCC interacts weakly with CREB and overlaps with two sequence
      motifs (TTGTTGAC and CCAAT) that bind winged helix-like proteins and the
      transcription factor NF-Y, respectively. Transient transfection of wild-type and
      mutant insulin CRE-reporter fusion genes and the inactivation of cellular CREB or
      NF-Y by overexpression of the dominant negative mutants KCREB or NF-YA29,
      respectively, indicate that cAMP inducibility of the insulin CRE is mediated by
      CREB or closely related proteins; however, NF-Y binding to the insulin CRE
      confers constitutive, basal activity and decreases the ability of CREB to mediate
      cAMP-stimulated transcription and calcium responsiveness. Results from these
      studies demonstrate that NF-Y binds to the insulin CRE and modulates the function
      of CREB. Together with the nonpalindromic sequence of the CRE octamer motif, the
      interaction of NF-Y with CREB may be responsible for the gene-specific
      transcriptional activity of the insulin CRE and explain why it has considerable
      basal activity but is less responsive to cAMP stimulation than others.

PMID- 9660818
TI  - Characterization of Pak2p, a pleckstrin homology domain-containing, p21-activated
      protein kinase from fission yeast.
AB  - p21-activated kinases (PAKs) bind to and are activated by Rho family GTPases such
      as Cdc42 and Rac. Since these GTPases play key roles in regulating cell polarity,
      stress responses, and cell cycle progression, the ability of PAK to affect these
      processes has been examined. We previously showed that fission yeast pak1+
      encodes an essential protein that affects mating and cell polarity. Here, we
      characterize a second pak gene (pak2+) from Schizosaccharomyces pombe. Like the
      Saccharomyces cerevisiae proteins Cla4p and Skm1p, fission yeast Pak2p contains
      an N-terminal pleckstrin homology domain in addition to a p21-binding domain and
      a protein kinase domain that are common to other members of the PAK family.
      Unlike pak1+, pak2(+) is not essential for vegetative growth or for mating in S.
      pombe. Overexpression of the wild-type pak2+ allele suppresses the lethal growth
      defect associated with deletion of pak1+, and this suppression requires both the
      pleckstrin homology- and the p21-binding domains of Pak2p, as well as kinase
      activity. A substantial fraction of Pak2p is associated with membranous
      components, an association mediated both by the pleckstrin homology- and by the
      p21-binding domains. These results show that S. pombe encodes at least two pak
      genes with distinct functions and suggest that the membrane localization of
      Pak2p, directed by its interactions with membrane lipids and Cdc42p, is critical
      to its biological activity.

PMID- 9660820
TI  - DNA binding characteristics of RegA. A constitutively active anaerobic activator
      of photosynthesis gene expression in Rhodobacter capsulatus.
AB  - In the purple non-sulfur bacterium Rhodobacter capsulatus, RegA and RegB comprise
      a two-component regulatory system that is required for maximal anaerobic
      transcription of key photosynthesis genes. RegB is a sensor kinase that uses ATP
      to phosphorylate its cognate response regulator, RegA. The mechanism under which
      RegA approximately P influences transcription of target genes has been unclear
      given that past attempts to demonstrate DNA binding activity by isolated RegA
      have failed. This led to a model invoking a role for RegA approximately P as an
      intermediate in a more complex multicomponent phosphoryl transfer cascade. In the
      present study, we describe the isolation of a mutant version of RegA (RegA*)
      which promotes high level expression of photosynthesis genes independent of RegB.
      DNase I footprint analyses show that purified RegA* binds to the promoters of the
      puf and puc operons at locations that are consistent with RegA functioning as a
      transcriptional activator for these operons. We conclude that RegA functions,
      like most members of the response regulator family, as a DNA-binding protein that
      directly affects the expression of its target genes.

PMID- 9660821
TI  - Chemotactic properties of angiopoietin-1 and -2, ligands for the endothelial
      specific receptor tyrosine kinase Tie2.
AB  - Angiopoietin-1 and its putative natural antagonist, angiopoietin-2, were recently
      isolated, and the critical role of angiopoietin-1 in embryogenic angiogenesis was
      demonstrated by targeted gene disruption. Specific biological effects of
      angiopoietin-1, however, have yet to be defined. In this study we demonstrate
      that angiopoietin-1, but not angiopoietin-2, is chemotactic for endothelial
      cells. In contrast, angiopoietin-1 as well as angiopoietin-2 exhibit no
      proliferative effect on endothelial cells. Excess soluble Tie2, but not Tie1
      receptor, abolish the chemotactic response of endothelial cells toward
      angiopoietin-1. Angiopoietin-2 dose-dependently blocks directed migration toward
      angiopoietin-1, consistent with the role of angiopoietin-2 as a naturally
      occurring inhibitor of angiopoietin-1. Fibroblasts stably transfected with Tie2
      receptor exhibit chemotactic responses for both angiopoietin-1 and angiopoietin
      2. Fibroblasts stably expressing a transfected chimeric receptor consisting of
      the ectodomain of TrkC fused to the cytoplasmic domain of Tie2 also exhibit a
      chemotactic response to neurotrophin 3 (NT-3), a specific ligand for TrkC.
      Endothelial cells are shown to express angiopoietin-2 mRNA and protein,
      indicating the potential for autocrine activation of angiopoietin/Tie2. Finally,
      the demonstration that Tie2 as well as angiopoietin-1 are expressed in normal
      human arteries and veins suggests that the role of angiopoietin/Tie2 may extend
      beyond embryonic angiogenesis to maintaining integrity of the adult vasculature.

PMID- 9660822
TI  - Potent prostaglandin A1 analogs that suppress tumor cell growth through induction
      of p21 and reduction of cyclin E.
AB  - Although the cyclopentenone prostaglandin A1 (PGA1) is known to arrest the cell
      cycle at the G1 phase in vitro and to suppress tumor growth in vivo, its
      relatively weak activity limits its usefulness in cancer chemotherapy. In an
      attempt to develop antitumor drugs of greater potency and conspicuous biological
      specificity, we synthesized novel analogs based on the structure of PGA1. Of the
      newly synthesized analogs, 15-epi-delta7-PGA1 methyl ester (NAG-0092), 12-iso
      delta7-PGA1 methyl ester (NAG-0093), and ent-delta7-PGA1 methyl ester (NAG-0022)
      possess a cross-conjugated dienone structure around the five-member ring with
      unnatural configurations at C(12) and/or C(15) and were found to be far more
      potent than native PGA1 in inhibiting cell growth and causing G1 arrest in A172
      human glioma cells. These three analogs induced the expression of p21 at both RNA
      and protein levels in a time- and dose-dependent fashion. Kinase assays with A172
      cells treated with these analogs revealed that both cyclin A- and E-dependent
      kinase activities were markedly reduced, although cyclin D1-dependent kinase
      activity was unaffected. Immunoprecipitation-Western blot analysis showed that
      the decrease in cyclin A-dependent kinase activity was due to an increased
      association of p21 with cyclin A-cyclin-dependent kinase 2 complexes, whereas the
      decrease in cyclin E-dependent activity was due to a combined mechanism involving
      reduction in cyclin E protein itself and increased association of p21. Thus,
      these newly synthesized PGA1 analogs may prove to be powerful tools in cancer
      chemotherapy as well as in investigations of the structural basis of the
      antiproliferative activity of A series prostaglandins.

PMID- 9660824
TI  - Nuclear factor I (NFI) isoforms differentially activate simple versus complex NFI
      responsive promoters.
AB  - Promoter-specific differences in the function of transcription factors play a
      central role in the regulation of gene expression. We have measured the maximal
      transcriptional activation potentials of nuclear factor I (NFI) proteins encoded
      by each of the four identified NFI genes (NFI-A, -B, -C, and -X) by transient
      transfection in JEG-3 cells using two model NFI-dependent promoters: 1) a simple
      chimeric promoter containing a single NFI-binding site upstream of the adenovirus
      major late promoter (NFI-Ad), and 2) the more complex mouse mammary tumor virus
      long terminal repeat promoter. The relative activation potentials for the NFI
      isoforms differed between the two promoters, with NFI-X being the strongest
      activator of NFI-Ad and NFI-B being the strongest activator of the MMTV promoter.
      To determine if these promoter-specific differences in activation potential were
      due to the presence of glucocorticoid response elements (GREs), we added GREs
      upstream of the NFI-binding site in NFI-Ad. NFI-X remains the strongest activator
      of the GRE containing simple promoter, indicating that differences in relative
      activation potential are not due solely to the presence of GREs. Since NFI
      proteins bind to DNA as dimers, we assessed the activation potentials of NFI
      heterodimers. Here, we show that NFI heterodimers have intermediate activation
      potentials compared with homodimers, demonstrating one potential mechanism by
      which different NFI proteins can regulate gene expression.

PMID- 9660823
TI  - Inhibition of phosphatidylinositol 3-kinase activity by adenovirus-mediated gene
      transfer and its effect on insulin action.
AB  - Phosphatidylinositol 3-kinase (PI 3-K) is implicated in cellular events including
      glucose transport, glycogen synthesis, and protein synthesis. It is activated in
      insulin-stimulated cells by binding of the Src homology 2 (SH2) domains in its 85
      kDa regulatory subunit to insulin receptor substrate-1 (IRS-1), and, others. We
      have previously shown that IRS-1-associated PI 3-kinase activity is not essential
      for insulin-stimulated glucose transport in 3T3-L1 adipocytes, and that alternate
      pathways exist in these cells. We now show that adenovirus-mediated
      overexpression of the p85N-SH2 domain in these cells behaves in a dominant
      negative manner, interfering with complex formation between endogenous PI 3-K and
      its SH2 binding targets. This not only inhibited insulin-stimulated IRS-1
      associated PI 3-kinase activity, but also completely blocked anti-phosphotyrosine
      associated PI 3-kinase activity, which would include the non-IRS-1-associated
      activity. This resulted in inhibition of insulin-stimulated glucose transport,
      glycogen synthase activity and DNA synthesis. Further, Ser/Thr phosphorylation of
      downstream molecules Akt and p70 S6 kinase was inhibited. However, co-expression
      of a membrane-targeted p110(C) with the p85N-SH2 protein rescued glucose
      transport, supporting our argument that the p85N-SH2 protein specifically blocks
      insulin-mediated PI 3-kinase activity, and, that the signaling pathways
      downstream of PI 3-kinase are intact. Unexpectedly, GTP-bound Ras was elevated in
      the basal state. Since p85 is known to interact with GTPase-activating protein in
      3T3-L1 adipocytes, the overexpressed p85N-SH2 peptide could titrate out cellular
      GTPase-activating protein by direct association, such that it is unavailable to
      hydrolyze GTP-bound Ras. However, insulin-induced mitogen-activated protein
      kinase phosphorylation was inhibited. Thus, PI 3-kinase may be required for this
      action at a step independent of and downstream of Ras. We conclude that, in 3T3
      L1 adipocytes, non-IRS-1-associated PI 3-kinase activity is crucial for insulin's
      metabolic signaling, and that overexpressed p85N-SH2 protein inhibits a variety
      of insulin's ultimate biological effects.

PMID- 9660825
TI  - Splicing of two internal and four carboxyl-terminal alternative exons in
      nonmuscle tropomyosin 5 pre-mRNA is independently regulated during development.
AB  - Four nonmuscle tropomyosin isoforms have been reported to be produced from the
      rat Tm5 gene by alternative splicing (Beisel, K. W., and Kennedy, J. E. (1994)
      Gene (Amst.) 145, 251-256). In order to detect additional isoforms that might be
      expressed from that gene, we used reverse transcriptase-polymerase chain reaction
      assays and evaluated the presence of all product combinations of two alternative
      internal exons (6a and 6b) and four carboxyl-terminal exons (9a, 9b, 9c, and 9d)
      in developing and adult rat brain. We identified five different combinations for
      exon 9 (9a + 9b, 9a + 9c, 9a + 9d, 9c, and 9d), and the exon combinations 9a + 9c
      and 9a + 9d were previously unreported. Each of these combinations existed with
      both exon 6a and exon 6b. Thus, the rat brain generates at least 10 different
      isoforms from the Tm5 gene. Northern blot hybridization with alternative exon
      specific probes revealed that these isoforms were also expressed in a number of
      different adult rat tissues, although some exons are preferentially expressed in
      particular tissues. Studies of regulation of the 10 different Tm5 isoform mRNAs
      during rat brain development indicated that no two isoforms are coordinately
      accumulated. Furthermore, there is a developmental switch in the use of exon 6a
      to exon 6b from embryonic to adult isoforms. TM5 protein isoforms show a
      differential localization in the adult cerebellum.

PMID- 9660826
TI  - A linker region of the yeast zinc cluster protein leu3p specifies binding to
      everted repeat DNA.
AB  - Yeast zinc cluster proteins form a major class of yeast transcriptional
      regulators. They usually bind as homodimers to target DNA sequences, with each
      monomer recognizing a CGG triplet. Orientation and spacing between the CGG
      triplet specifies the recognition sequence for a given zinc cluster protein. For
      instance, Gal4p binds to inverted CGG triplets spaced by 11 base pairs whereas
      Ppr1p recognizes a similar motif but with a spacing of 6 base pairs. Hap1p,
      another member of this family, binds to a direct repeat consisting of two CGG
      triplets. Other members of this family, such as Leu3p, also recognize CGG
      triplets but when oriented in opposite directions, an everted repeat. This
      implies that the two zinc clusters of Leu3p bound to an everted repeat must be
      oriented in opposite directions to those of Gal4p or Ppr1p bound to inverted
      repeats. In order to map the domain responsible for proper orientation of the
      zinc clusters of Leu3p, we constructed chimeric proteins between Leu3p and Ppr1p
      and tested their binding to a Leu3p and a Ppr1p site. Our results show that the
      linker region, which bridges the zinc cluster to the dimerization domain,
      specifies binding of Leu3p to an everted repeat. We propose that the Leu3p linker
      projects the two zinc clusters of a Leu3p homodimer in opposite directions
      allowing binding to everted repeats.

PMID- 9660827
TI  - The rluC gene of Escherichia coli codes for a pseudouridine synthase that is
      solely responsible for synthesis of pseudouridine at positions 955, 2504, and
      2580 in 23 S ribosomal RNA.
AB  - Escherichia coli ribosomal RNA contains 10 pseudouridines, one in the 16 S RNA
      and nine in the 23 S RNA. Previously, the gene for the synthase responsible for
      the 16 S RNA pseudouridine was identified and cloned, as was a gene for a
      synthase that makes a single pseudouridine in 23 S RNA. The yceC open reading
      frame of E. coli is one of a set of genes homologous to these previously
      identified ribosomal RNA pseudouridine synthases. In this work, the gene was
      cloned, overexpressed, and shown to code for a pseudouridine synthase able to
      react with in vitro transcripts of 23 S ribosomal RNA. Deletion of the gene and
      analysis of the 23 S RNA from the deletion strain for the presence of
      pseudouridine at its nine known sites revealed that this synthase is solely
      responsible in vivo for the synthesis of three of the nine pseudouridine
      residues, at positions 955, 2504, and 2580. Therefore, this gene has been renamed
      rluC. Despite the absence of one-third of the normal complement of
      pseudouridines, there was no change in the exponential growth rate in either LB
      or M-9 medium at temperatures ranging from 24 to 42 degrees C. From this work and
      our previous studies, we have now identified three synthases that account for 50%
      of the pseudouridines in the E. coli ribosome.

PMID- 9660828
TI  - Switching of platelet-activating factor acetylhydrolase catalytic subunits in
      developing rat brain.
AB  - In a previous study, we demonstrated that Platelet-activating Factor (PAF)
      acetylhydrolase purified from bovine brain cortical cytosol consists of two
      mutually homologous catalytic subunits (alpha1 and alpha2) and one putative
      regulatory beta subunit. The latter is a product of the LIS1 gene, which is
      defective in the Miller-Dieker syndrome, a form of lissencephaly. In this study,
      we examined the expression patterns of these three subunits in the developing rat
      brain. All three subunits were expressed in embryonic brain, whereas only alpha2
      and beta subunit were detected in the adult brain by Western blotting.
      Biochemical analyses revealed that the alpha1/alpha2 heterodimer and
      alpha2/alpha2 homodimer are major catalytic units of embryonic and adult brain
      PAF acetylhydrolases, respectively. The alpha1 transcript and protein were
      detected predominantly in embryonic and postnatal neural tissues, such as the
      brain and spinal cord. Furthermore, we found using primary cultured cells
      isolated from neonatal rat brain that alpha1 protein were expressed only in
      neurons but not in glial cells and fibroblasts. In contrast, alpha2 and beta
      transcripts and proteins were detected both in neural and non-neural tissues, and
      their expression level was almost constant from fetal stages through adulthood.
      These results indicate that alpha1 expression is restricted to actively migrating
      neurons in rats and that switching of catalytic subunits from the alpha1/alpha2
      heterodimer to the alpha2/alpha2 homodimer occurred in these cells during brain
      development, suggesting that PAF acetylhydrolase plays a role(s) in neuronal
      migration.

PMID- 9660829
TI  - Complex formation by all five homologues of mammalian translation initiation
      factor 3 subunits from yeast Saccharomyces cerevisiae.
AB  - The PRT1, TIF34, GCD10, and SUI1 proteins of Saccharomyces cerevisiae were found
      previously to copurify with eukaryotic translation initiation factor 3 (eIF3)
      activity. Although TIF32, NIP1, and TIF35 are homologous to subunits of human
      eIF3, they were not known to be components of the yeast factor. We detected
      interactions between PRT1, TIF34, and TIF35 by the yeast two-hybrid assay and in
      vitro binding assays. Discrete segments (70-150 amino acids) of PRT1 and TIF35
      were found to be responsible for their binding to TIF34. Temperature-sensitive
      mutations mapping in WD-repeat domains of TIF34 were isolated that decreased
      binding between TIF34 and TIF35 in vitro. The lethal effect of these mutations
      was suppressed by increasing TIF35 gene dosage, suggesting that the TIF34-TIF35
      interaction is important for TIF34 function in translation. Pairwise in vitro
      interactions were also detected between PRT1 and TIF32, TIF32 and NIP1, and NIP1
      and SUI1. Furthermore, PRT1, NIP1, TIF34, TIF35, and a polypeptide with the size
      of TIF32 were specifically coimmunoprecipitated from the ribosomal salt wash
      fraction. We propose that all five yeast proteins homologous to human eIF3
      subunits are components of a stable heteromeric complex in vivo and may comprise
      the conserved core of yeast eIF3.

PMID- 9660830
TI  - Characterization of the N-acetylglucosaminyltransferase activity involved in the
      biosynthesis of the Staphylococcus epidermidis polysaccharide intercellular
      adhesin.
AB  - The polysaccharide intercellular adhesin (PIA) is an important factor in the
      colonization of medical devices by Staphylococcus epidermidis. The genes encoding
      PIA production are organized in the icaADBC (intercellular adhesion) operon. To
      study the function of the individual genes, we have established an in vitro assay
      with UDP-N-acetylglucosamine, the substrate for PIA biosynthesis, and analyzed
      the products by thin-layer chromatography and mass spectrometry. IcaA alone
      exhibited a low N-acetylglucosaminyltransferase activity and represents the
      catalytic enzyme. Coexpression of icaA with icaD led to a significant increase in
      activity. The newly identified icaD gene is located between icaA and icaB and
      overlaps both genes. N-Acetylglucosamine oligomers produced by IcaAD reached a
      maximal length of 20 residues. Only when icaA and icaD were expressed together
      with icaC were oligomer chains that react with PIA-specific antiserum
      synthesized. IcaA and IcaD are located in the cytoplasmic membrane, and IcaC also
      has all the structural features of an integral membrane protein. These results
      indicate a close interaction between IcaA, IcaD, and IcaC. Tunicamycin and
      bacitracin did not affect the in vitro synthesis of PIA intermediates or the
      complete PIA biosynthesis in vivo, suggesting that a undecaprenyl phosphate
      carrier is not involved. IcaAD represents a novel protein combination among beta
      glycosyltransferases.

PMID- 9660831
TI  - The C terminus of the hepatitis B virus e antigen precursor is required for a
      tunicamycin-sensitive step that promotes efficient secretion of the antigen.
AB  - The Hepatitis B virus encodes the secreted e antigen (HBe) whose function in the
      viral life cycle is unknown. HBe derives from a 25-kDa precursor that is directed
      to the secretory pathway. After cleavage of the signal sequence, the resulting 22
      kDa protein (P22) is processed in a post-endoplasmic reticulum compartment to
      mature HBe by removal of the 34-amino acid C-terminal domain. The efficiency of
      HBe secretion is specifically decreased in cells grown in the presence of
      tunicamycin, an inhibitor of N-glycosylation. Inasmuch as HBe precursor is not N
      glycosylated, our data suggest that a cellular tunicamycin-sensitive protein
      increases the intracellular transport through the HBe secretory pathway. The
      study of the secretion of HBe derived from C-terminal-truncated precursors
      demonstrates that the tunicamycin-sensitive secretion absolutely requires a part
      of the C-terminal region that is removed to form mature HBe, indicating that the
      cellular tunicamycin-sensitive protein increases the efficiency of the
      intracellular transport of P22. We have also shown that the Escherichia coli beta
      galactosidase can be secreted when fused to the HBe precursor signal sequence and
      that the P22 C-terminal domain renders the secretion of this reporter protein
      also tunicamycin-sensitive.

PMID- 9660832
TI  - Translation eukaryotic initiation factor 4G recognizes a specific structural
      element within the internal ribosome entry site of encephalomyocarditis virus
      RNA.
AB  - A complex of eukaryotic initiation factors (eIFs) 4A, 4E, and 4G (collectively
      termed eIF4F) plays a key role in recruiting mRNAs to ribosomes during
      translation initiation. The site of ribosomal entry onto most mRNAs is determined
      by interaction of the 5'-terminal cap with eIF4E; eIFs 4A and 4G may facilitate
      ribosomal entry by modifying mRNA structure near the cap and by interacting with
      ribosome-associated factors. eIF4G recruits uncapped encephalomyocarditis virus
      (EMCV) mRNA to ribosomes without the involvement of eIF4E by binding directly to
      the approximately 450-nucleotide long EMCV internal ribosome entry site (IRES).
      We have used chemical and enzymatic probing to map the eIF4G binding site to a
      structural element within the J-K domain of the EMCV IRES that consists of an
      oligo(A) loop at the junction of three helices. The oligo(A) loop itself is not
      sufficient to form stable complexes with eIF4G since alteration of its structural
      context abolished its interaction with eIF4G. Addition of wild type or trans
      dominant mutant forms of eIF4A to binary IRES.eIF4G complexes did not further
      alter the pattern of chemical/enzymatic modification of the IRES.

PMID- 9660833
TI  - Growth factors and insulin stimulate tyrosine phosphorylation of the 51C/SHIP2
      protein.
AB  - Antibodies raised against the 51C/SHIP2 inositol polyphosphate 5'-phosphatase
      were used to examine the effects of growth factors and insulin on the metabolism
      of this protein. Immunoblot analysis revealed that the 51C/SHIP2 protein was
      widely expressed in fibroblast and nonhematopoietic tumor cell lines, unlike the
      SHIP protein, which was found only in cell lines of hematopoietic origin. The
      51C/SHIP2 antiserum precipitated a protein of approximately 145 kDa along with an
      activity which hydrolyzed phosphatidylinositol 3,4, 5-trisphosphate to
      phosphatidylinositol 3,4-bisphosphate. Tyrosine phosphorylation of the 51C/SHIP2
      protein occurred in response to treatment of cells with epidermal growth (EGF),
      platelet-derived growth factor (PDGF), nerve growth factor (NGF), insulin-like
      growth factor-1 (IGF-1), or insulin. EGF and PDGF induced transient tyrosine
      phosphorylation of 51C/SHIP2, with maximal tyrosine phosphorylation occurring at
      5-10 min following treatment and returning to near basal levels within 20 min. In
      contrast, treatment of cells with NGF, IGF-1, or insulin resulted in prolonged
      tyrosine phosphorylation of 51C/SHIP2 protein, with 40-80% maximal
      phosphorylation sustained for up to 2 h following agonist treatment. The kinetics
      of activation of the Akt/PKB protein kinase by the various factors correlated
      well with the kinetics of tyrosine phosphorylation of 51C/SHIP2. EGF, NGF, and
      PDGF stimulated the association of 51C/SHIP2 protein with the Shc adapter
      protein; however, no Shc could be detected in 51C/SHIP2-immune precipitates from
      cells treated with IGF-1 or insulin. The data suggest that 51C/SHIP2 may play a
      significant role in regulation of phosphatidylinositol 3'-kinase signaling by
      growth factors and insulin.

PMID- 9660834
TI  - The basolateral localization signal of the follicle-stimulating hormone receptor.
AB  - The follicle-stimulating hormone receptor (FSHR) is physiologically localized in
      the basolateral compartment of the membrane of Sertoli cells. This localization
      is also observed when the receptor is experimentally expressed in Madin-Darby
      canine kidney cells. We thus used in vitro mutagenesis and transfection into
      these polarized cells to delineate the basolateral localization signal of the
      receptor. The signal was localized in the C-terminal tail of the intracellular
      domain (amino acids 678-691) at a marked distance of the membrane. Mutation of
      individual amino acids highlighted the importance of Tyr684 and Leu689. The 14
      amino acid sequence was grafted onto the p75 neurotrophin receptor and redirected
      this apical protein to the basolateral cell membrane compartment. Deletion of
      amino acids 677-695 did not modify the internalization of the FSHR, showing that
      the basolateral localization signal of the FSHR is not colinear with its
      internalization signal.

PMID- 9660835
TI  - FGF2-Heparin co-crystal complex-assisted design of mutants FGF1 and FGF7 with
      predictable heparin affinities.
AB  - The co-crystal structures of FGF2 and heparin-derived tetra- and hexasaccharides
      demonstrated the existence of high and low affinity contact residues that are
      likely to be involved in heparin binding (Faham, S., Hileman, R. E., Fromm, J.
      R., Linhardt, R. J., and Rees, D. C. (1996) Science 271, 1116-1120). To study the
      role of these putative contact residues, we chose three fibroblast growth factor
      family members with distinct heparin affinities for comparative mutagenesis
      studies. Only one amino acid significantly differed between FGF1 and FGF2 and was
      mutated, FGF1-31K. FGF7, also called keratinocyte growth factor, was mutated to
      mimic either FGF1 or FGF2 at two of the putative high contact points termed FGF7
      1 and FGF7-2, respectively. FGF2 has higher apparent heparin affinity than FGF1
      or FGF7, and FGF1 has higher heparin affinity than FGF7. All three mutants showed
      an increase in apparent heparin affinity compared with wild types. FGF7-1 has a
      lower apparent heparin affinity than FGF7-2, analogous to wild type FGF1 and
      FGF2. The FGF1-31K mutant showed no change in mitogenic activity, whereas the
      FGF7 mutants exhibited a decrease in activity. These results indicate that the co
      crystal structure of the FGF2-heparin complexes can be used to design a rational
      approach to the generation of mutants with defined affinities for heparin or
      heparan sulfate proteoglycans.

PMID- 9660836
TI  - Identification of a novel inhibitor of mitogen-activated protein kinase kinase.
AB  - The compound U0126 (1,4-diamino-2,3-dicyano-1, 4-bis[2-aminophenylthio]butadiene)
      was identified as an inhibitor of AP-1 transactivation in a cell-based reporter
      assay. U0126 was also shown to inhibit endogenous promoters containing AP-1
      response elements but did not affect genes lacking an AP-1 response element in
      their promoters. These effects of U0126 result from direct inhibition of the
      mitogen-activated protein kinase kinase family members, MEK-1 and MEK-2.
      Inhibition is selective for MEK-1 and -2, as U0126 shows little, if any, effect
      on the kinase activities of protein kinase C, Abl, Raf, MEKK, ERK, JNK, MKK-3,
      MKK-4/SEK, MKK-6, Cdk2, or Cdk4. Comparative kinetic analysis of U0126 and the
      MEK inhibitor PD098059 (Dudley, D. T., Pang, L., Decker, S. J., Bridges, A. J.,
      and Saltiel, A. R. (1995) Proc. Natl. Acad. Sci U. S. A. 92, 7686-7689)
      demonstrates that U0126 and PD098059 are noncompetitive inhibitors with respect
      to both MEK substrates, ATP and ERK. We further demonstrate that the two
      compounds bind to deltaN3-S218E/S222D MEK in a mutually exclusive fashion,
      suggesting that they may share a common or overlapping binding site(s).
      Quantitative evaluation of the steady state kinetics of MEK inhibition by these
      compounds reveals that U0126 has approximately 100-fold higher affinity for
      deltaN3-S218E/S222D MEK than does PD098059. We further tested the effects of
      these compounds on the activity of wild type MEK isolated after activation from
      stimulated cells. Surprisingly, we observe a significant diminution in affinity
      of both compounds for wild type MEK as compared with the deltaN3-S218E/S222D
      mutant enzyme. These results suggest that the affinity of both compounds is
      mediated by subtle conformational differences between the two activated MEK
      forms. The MEK affinity of U0126, its selectivity for MEK over other kinases, and
      its cellular efficacy suggest that this compound will serve as a powerful tool
      for in vitro and cellular investigations of mitogen-activated protein kinase
      mediated signal transduction.

PMID- 9660837
TI  - Molecular cloning and characterization of the mouse tag7 gene encoding a novel
      cytokine.
AB  - Cloning of the mouse tag7 gene encoding a novel cytokine is described. The Tag7
      protein consists of 182 amino acids. Genomic organization of the tag7 gene and
      its promoter region remind those of the genes of the tumor necrosis factor locus,
      although the tag7 gene is not linked to this locus. The gene is located on
      chromosome 7 at the area that corresponds to band 7A3, which has genetic linkage
      with lupus-like disease in mouse models. tag7 transcription is essential for
      lymphoid organs. It is also detected in certain areas of lungs, brain, and
      intestine and in some tumors. Tag7 protein is detectable in both cell-associated
      and soluble forms. The soluble form of Tag7 triggers apoptosis in mouse L929
      cells in vitro and does not involve NF-kappaB activation. The relationship
      between Tag7 and tumor necrosis factor family of ligands is discussed.

PMID- 9660838
TI  - Transcriptional activity of heat shock factor 1 at 37 degrees C is repressed
      through phosphorylation on two distinct serine residues by glycogen synthase
      kinase 3 and protein kinases Calpha and Czeta.
AB  - Heat shock factor 1 (HSF1) is the key transcriptional regulator of the heat shock
      genes that protect cells from environmental stress. However, because heat shock
      gene expression is deleterious to growth and development, we have examined
      mechanisms for HSF1 repression at growth temperatures, focusing on the role of
      phosphorylation. Mitogen-activated protein kinases (MAPKs) of the ERK family
      phosphorylate HSF1 and represses transcriptional function. The mechanism of
      repression involves initial phosphorylation by MAP kinase on serine 307, which
      primes HSF1 for secondary phosphorylation by glycogen synthase kinase 3 on a key
      residue in repression (serine 303). In vivo expression of glycogen synthase
      kinase 3 alpha or beta thus represses HSF1 through phosphorylation of serine 303.
      HSF1 is also phosphorylated by MAPK in vitro on a second residue (serine 363)
      adjacent to activation domain 1, and this residue is additionally phosphorylated
      by protein kinase C. In vivo, HSF1 is repressed through phosphorylation of this
      residue by protein kinase Calpha or -zeta but not MAPK. Regulation at 37 degrees
      C, therefore, involves the action of three protein kinase cascades that repress
      HSF1 through phosphorylation of serine residues 303, 307, and 363 and may promote
      growth by suppressing the heat shock response.

PMID- 9660839
TI  - The transcription factor NF-kappaB/p50 interacts with the blk gene during B cell
      activation.
AB  - The B cell-specific transcription factor Pax-5 has been shown previously to
      interact with the promoter of the blk gene in vitro. blk encodes a tyrosine
      kinase associated with the B cell receptor, which is expressed during the early
      but not the final stages of B cell development. To investigate whether Pax-5
      regulates expression of the blk gene in vivo during B cell development and/or
      activation, Pax-5a was overexpressed in B cell lines. Increases in blk promoter
      activity using a chloramphenicol acetyltransferase reporter gene system suggested
      a role for Pax-5a as a transcriptional activator. Subsequent site-specific
      mutagenesis studies showed that mutations of the Pax-5 binding site on blk
      significantly alter promoter activity, although results suggested that other
      factors could bind to this region as well. Using mobility shift assays, we
      detected an inducible transcription factor that interacts strongly with a
      sequence overlapping the Pax-5 site on the blk promoter and identified this as a
      homodimer of NF-kappaB/p50, a member of the NF-kappaB/Rel family of transcription
      factors. This factor was present at high levels in lipopolysaccharide-activated
      normal B cells and in plasma cell lines but either at low levels or undetectable
      levels in resting normal B cells or pre-B or mature B cell lines. In contrast,
      lipopolysaccharide induction of a pre-B cell line (703/Z) induced a complex that
      contained both NF-kappaB/p50 and p65. These studies suggest that different NF
      kappaB complexes are able to interact with a sequence overlapping the Pax-5 site
      on the blk promoter and that the relative levels of "bound" factor influence
      levels of blk expression. Since p50 homodimers and p50/p65 heterodimers of the NF
      kappaB complex should have opposing effects on blk transcription, this could
      provide a mechanism to differentially regulate blk expression during B cell
      development and activation.

PMID- 9660840
TI  - Cloning of a novel C-type lectin expressed by murine macrophages.
AB  - We report the cloning of a novel macrophage-restricted C-type lectin by
      differential display polymerase chain reaction. This molecule, named mouse
      macrophage C-type lectin, is a 219-amino acid, type II transmembrane protein with
      a single extracellular C-type lectin domain. Northern blot analysis indicates
      that it is expressed in cell lines and normal mouse tissues in a macrophage
      restricted manner. The cDNA and genomic sequences of mouse macrophage C-type
      lectin indicate that it is related to the Group II animal C-type lectins. The mcl
      gene locus has been mapped between the genes for the interleukin-17 receptor and
      CD4 on mouse chromosome 6, the same chromosome as the mouse natural killer cell
      gene complex.

PMID- 9660841
TI  - QacR is a repressor protein that regulates expression of the Staphylococcus
      aureus multidrug efflux pump QacA.
AB  - The Staphylococcus aureus QacA protein is a multidrug transporter that confers
      resistance to a broad range of antimicrobial agents via proton motive force
      dependent efflux of the compounds. Primer extension analysis was performed to map
      the transcription start points of the qacA and divergently transcribed qacR
      mRNAs. Each gene utilized a single promoter element, the locations of which were
      confirmed by site-directed mutagenesis. Fusions of the qacA and qacR promoters to
      a chloramphenicol acetyl transferase reporter gene were used to demonstrate that
      QacR is a trans-acting repressor of qacA transcription that does not autoregulate
      its own expression. An inverted repeat overlapping the qacA transcription start
      site was shown to be the operator sequence for control of qacA gene expression.
      Removal of one half of the operator prevented QacR-mediated repression of the
      qacA promoter. Purified QacR protein bound specifically to this operator sequence
      in DNase I-footprinting experiments. Importantly, addition of diverse QacA
      substrates was shown to induce qacA expression in vivo, as well as inhibit
      binding of QacR to operator DNA in vitro, by using gel-mobility shift assays.
      QacR therefore appears to interact directly with structurally dissimilar inducing
      compounds that are substrates of the QacA multidrug efflux pump.

PMID- 9660842
TI  - Characterization of the selectivity and mechanism of human cytochrome P450
      inhibition by the human immunodeficiency virus-protease inhibitor nelfinavir
      mesylate.
AB  - In vitro studies with human liver microsomes and P450 probe substrates were
      performed to characterize selectivity and mechanism of cytochrome P450 inhibition
      by nelfinavir mesylate. At therapeutic concentrations (steady-state plasma
      concentrations approximately 4 microM), nelfinavir was found to be a competitive
      inhibitor of only testosterone 6beta-hydroxylase (CYP3A4) with a Ki concentration
      of 4. 8 microM. At supratherapeutic concentrations, nelfinavir competitively
      inhibited dextromethorphan O-demethylase (CYP2D6), S-mephenytoin 4-hydroxylase
      (CYP2C19), and phenacetin O-deethylase (CYP1A2) with Ki concentrations of 68,
      126, and 190 microM, respectively. Nelfinavir did not appreciably inhibit
      tolbutamide 4-hydroxylase (CYP2C9), paclitaxel 6alpha-hydroxylase (CYP2C8), or
      chlorzoxaxone 6beta-hydroxylase (CYP2E1) activities. The inhibitory potency of
      nelfinavir toward CYP3A4 suggested the possibility of in vivo inhibition of this
      isoform, whereas in vivo inhibition of other P450s was considered unlikely. In a
      one-sequence crossover study in 12 healthy volunteers, nelfinavir inhibited the
      elimination of the CYP3A substrate terfenadine and the carboxylate metabolite of
      terfenadine. The 24-hr urinary recoveries of 6beta-hydroxycortisol were reduced
      by an average of 27% during nelfinavir treatment, consistent with CYP3A
      inhibition by nelfinavir. Inhibition of CYP3A4 by nelfinavir in vitro was NADPH
      dependent requiring the catalytic formation of a metabolite or a metabolic
      intermediate. The catechol metabolite of nelfinavir (M3) was considered unlikely
      to be responsible for inhibition as the addition of catechol O-methyl
      transferase, S-adenosyl methionine, and ascorbic acid to the preincubation
      mixture did not protect against the loss of testosterone 6beta-hydroxylase
      activity. Also, the addition of M3 to human liver microsomes did not inhibit
      CYP3A4. Although incubations with nelfinavir showed a time- and concentration
      dependent loss of CYP3A4 activity, the partial or complete recovery of enzyme
      activity upon dialysis indicated that inhibition was reversible. Microsomal
      incubations with nelfinavir and NADPH did not result in a loss of spectral P450
      content compared with the NADPH control. Glutathione, N-acetylcysteine, and
      catalase did not attenuate CYP3A4 inhibition by nelfinavir. Collectively, these
      results suggest that the probable mechanism for CYP3A4 inhibition by nelfinavir
      is a transient metabolic intermediate or stable metabolite that coordinates
      tightly but reversibly to the heme moiety of the P450.

PMID- 9660843
TI  - Minimal interaction between fluoxetine and multiple-dose zolpidem in healthy
      women.
AB  - The objective was to evaluate possible pharmacokinetic and pharmacodynamic
      interactions for repeated nightly zolpidem dosing with fluoxetine. Twenty-nine
      healthy female volunteers (mean age, 25. 6 years) received zolpidem (10 mg) and
      fluoxetine (20 mg) in the following open design: zolpidem on night 1 followed by
      1 washout day, a daily morning dose of fluoxetine on days 3 through 27, and a
      morning dose of fluoxetine plus an evening dose of zolpidem on days 28 through
      32. Plasma levels of zolpidem, fluoxetine, and norfluoxetine were determined at
      the transitions from one regimen to the next. Morning psychomotor tests were
      performed on days 1, 2, 28, 29, and 33. Steady-state plasma concentrations of
      fluoxetine/norfluoxetine were reached by day 24 of fluoxetine dosing. No
      significant differences in any pharmacokinetic parameters for fluoxetine and
      norfluoxetine were observed between day 27 and day 32. There were no significant
      differences in AUC, maximal plasma concentration, or time to maximal
      concentration parameters for zolpidem plasma concentrations among nights 1, 28,
      and 32. There was a statistically significantly increased t1/2 for zolpidem on
      night 32, compared with night 28 (3.64 and 3.29 hr, respectively). There were no
      significant differences in the next-morning Digit Symbol Substitution Test
      performance at any time in the study. Both zolpidem and fluoxetine were well
      tolerated alone or during coadministration. These findings indicate the absence
      of clinically significant pharmacokinetic or pharmacodynamic interactions between
      fluoxetine and zolpidem (five consecutive doses) when the drugs are
      coadministered to healthy women. Therefore, based on these observations, short
      term cotherapy with fluoxetine (20 mg) and zolpidem (10 mg) appears safe.

PMID- 9660844
TI  - Reversible fatty acid conjugation of budesonide. Novel mechanism for prolonged
      retention of topically applied steroid in airway tissue.
AB  - A high airway concentration might be required for the antiasthmatic efficacy of
      inhaled glucocorticosteroids (GCS). The topical uptake and retention of GCS in
      airway tissue were compared for GCS of the inhaled type [budesonide (BUD),
      fluticasone propionate (FP), and beclomethasone dipropionate (BDP)] and of the
      noninhaled type (dexamethasone and hydrocortisone). 3H-labeled GCS solutions were
      administered into rat airways by either perfusion of trachea in vivo,
      intratracheal instillation, or inhalation. Radioactivity was determined in the
      airway tissue, lung parenchyma, and plasma 20 min to 24 hr after exposure.
      Ethanol extracts of exposed tracheas were analyzed by HPLC. Exposed tracheas were
      also incubated in vitro in buffer, and the released radioactivity was analyzed by
      HPLC. BUD, FP, and BDP were equally well taken up into the airway tissue; their
      uptake was 25-130 times greater than that of dexamethasone and hydrocortisone.
      BUD was shown to form very lipophilic intracellular fatty acid esters (at carbon
      21) in the airway and lung tissue after topical application. In large airways 20
      min after administration, approximately 70-80% of retained BUD was conjugated.
      BUD stored in esterified form in the tissue was retained in large airways for a
      prolonged time, compared with FP and BDP, which do not form such conjugates. The
      fatty acid conjugation of BUD is reversible in vivo; BUD conjugates are gradually
      hydrolyzed and free BUD is regenerated. This reversible conjugation may improve
      airway selectivity, as well as prolong the local anti-inflammatory action of BUD
      in the airways and might be one explanation for why BUD is efficacious in the
      treatment of mild asthma when inhaled once daily.

PMID- 9660845
TI  - Metabolism of delavirdine, a human immunodeficiency virus type-1 reverse
      transcriptase inhibitor, by microsomal cytochrome P450 in humans, rats, and other
      species: probable involvement of CYP2D6 and CYP3A.
AB  - The metabolism of delavirdine was examined using liver microsomes from several
      species with the aim of comparing metabolite formation among species and
      characterizing the enzymes responsible for delavirdine metabolism. Incubation of
      10 microM [14C]delavirdine with either an S9 fraction from human jejunum or liver
      microsomes from rat, human, dog, or monkey followed by high pressure liquid
      chromatography analysis showed qualitatively similar metabolite profiles among
      species with the formation of three significant metabolites. The major metabolite
      was desalkyl delavirdine; however, the identity of MET-7 and MET-7a (defined by
      high pressure liquid chromatography elution) could not be unambiguously
      established, but they seem to be related pyridine hydroxy metabolites, most
      likely derived from 6'-hydroxylation of the pyridine ring. The apparent KM for
      delavirdine desalkylation activity ranged from 4.4 to 12.6 microM for human, rat,
      monkey, and dog microsomes, whereas Vmax ranged from 0.07 to 0.60 nmol/min/mg
      protein, resulting in a wide range of intrinsic clearance (6-135 microL/min/mg
      protein). Delavirdine desalkylation by microsomes pooled from several human
      livers was characterized by a KM of 6.8 +/- 0.8 microM and Vmax of 0. 44 +/- 0.01
      nmol/min/mg. Delavirdine desalkylation among 23 human liver microsomal samples
      showed a meaningful correlation (r = 0.96) only with testosterone 6beta
      hydroxylation, an indicator of CYP3A activity. Among ten human microsomal samples
      selected for uniform distribution of CYP3A activity, formation of MET-7 was
      strongly correlated with CYP3A activity (r = 0.95) and with delavirdine
      desalkylation (r = 0.98). Delavirdine desalkylation was catalyzed by cDNA
      expressed CYP2D6 (KM 10.9 +/- 0.8 microM) and CYP3A4 (KM 5.4 +/- 1.4 microM);
      however, only CYP3A4 catalyzed formation of MET-7 and MET-7a. Quinidine inhibited
      human liver microsomal delavirdine desalkylation by about 20%, indicating a minor
      role of CYP2D6. These findings suggest the potential for clinical interaction
      with coadministered drugs that are metabolized by or influence the activity of
      CYP3A or CYP2D6.

PMID- 9660846
TI  - Biotransformation of cerivastatin in mice, rats, and dogs in vivo.
AB  - Biotransformation of cerivastatin was investigated in mice, rats, and dogs in
      vivo using the 14C-labeled drug. Marked species differences exist, both in
      pathways and extent of cerivastatin metabolism. Unchanged drug, together with its
      lactone, predominates in dog plasma and represents 40% of the dose in the
      excreta, whereas in rat bile they account for approximately 10% of the dose. In
      mice, the drug is metabolized rapidly and almost completely. Biotransformation of
      cerivastatin occurs by three distinct phase I routes and by phase II conjugation
      with sugar-type moieties and taurine. Phase I routes are demethylation of the
      pyridinyl methyl ether, beta-oxidation of the 3,5-dihydroxy acid side chain, and
      reductive removal of the side chain 3-hydroxy group. In dogs, demethylation is
      the dominating phase I biotransformation. Phase II conjugation is equally
      important. In dog bile, different regioisomeric drug glucuronides and the
      benzylic glucuronide and glucoside conjugate of the demethylated drug were found.
      In rats, besides demethylation, beta-oxidation of the dihydroxy acid side chain
      followed by reductive removal of the 5-hydroxy group-is the major reaction. The
      resulting pentenoic acid derivatives are observed in plasma and liver homogenate.
      These metabolites are subsequently conjugated with taurine and excreted in the
      bile. This metabolic sequence is also important in mice. Furthermore, only in
      mice, cerivastatin is subject to reductive removal of the 3-hydroxy group,
      together with demethylation. The 5-hydroxyheptenoic acids formed predominate in
      plasma and liver homogenate, whereas the corresponding taurine conjugates are
      excreted in the bile.

PMID- 9660847
TI  - Calcium binding by human and rabbit serum paraoxonases. Structural stability and
      enzymatic activity.
AB  - Equilibrium dialysis and Scatchard plots were used to establish that human and
      rabbit paraoxonases both have two calcium binding sites. Independent-site and
      stepwise constant analyses were used to calculate a higher affinity site (Kd1) of
      3.6 +/- 0.9 x 10(-7) M for human A paraoxonase, and 1.4 +/- 0.5 x 10(-8) M for
      rabbit paraoxonase, and a lower affinity site (Kd2) of 6.6 +/- 1.2 x 10(-6) M for
      human A paraoxonase, and 5.3 +/- 0.94 x 10(-6) M for rabbit paraoxonase. In both
      species, the higher affinity sites were found to be essential to maintain
      hydrolytic activity; complete removal of calcium led to irreversible
      inactivation. The lower affinity sites were required for catalytic activity, and
      their binding of calcium was reversible. Experimentally estimated values of Kd2
      based on the concentration of calcium required to obtain half the maximum
      enzymatic activity were 3 microM for human A and B paraoxonases, and also in the
      order of 3 microM for rabbit paraoxonase, using three different substrates.
      Calcium was the only metal found that protects against denaturation and also
      confers hydrolytic activity with these two mammalian paraoxonases.

PMID- 9660848
TI  - Hepatic disposition and toxicity of cationized goat immunoglobulin G and fab
      fragments in isolated perfused rat liver.
AB  - Colchicine-specific goat IgG and Fab fragments were cationized by covalent
      coupling of hexamethylenediamine. The immunoreactivity of antibodies was not
      changed following cationization. The interaction of 125I-radiolabeled native
      (nIgG and nFab) and cationized immunoglobulin G (cIgG) and Fab fragments (cFab)
      with liver was investigated using isolated perfused rat liver (IPRL) and isolated
      rat hepatic parenchymal cells (PCs) and nonparenchymal cells (NPCs) in
      suspension. 125I-cIgG or 125I-cFab were more rapidly cleared from the perfusate
      than the corresponding native proteins. Both cIgG and cFab declined
      biexponentially over time in the perfusate. In contrast, the native IgG and Fab
      decreased monoexponentially. The half-lives of the initial and terminal phases
      were 5.2 +/- 1.6 min and 355.1 +/- 17.2 min for cIgG and 14.7 +/- 3.4 min and
      552.4 +/- 23.7 min for cFab. The terminal half-lives of nIgG (467.4 +/- 11.6 min)
      and nFab (880.1 +/- 39.6 min) were longer than those of cationized molecules. The
      biliary protein extraction ratio of cationized IgG and Fab was greater than that
      of native IgG and Fab: 0.13% (cIgG), 0.02% (nIgG), 0.23% (cFab), and 0.17%
      (nFab). The uptake of cIgG and cFab by both PCs and NPCs was dose-dependent and
      was about 6-fold and 8-fold higher than that of their native counterparts,
      respectively. Throughout the experiment, liver viability was determined, and no
      toxicity was observed according to physiological analysis (bile flow rate, portal
      vein pressure, and pH) and biochemical analysis (glucose and hepatic enzymes:
      alanine transaminase, aspartate transaminase, lactate dehydrogenase) in
      perfusate.

PMID- 9660849
TI  - Pharmacokinetics of an antisense oligonucleotide injected intravitreally in
      monkeys.
AB  - The kinetics of an intravitreally administered phosphorothioate oligonucleotide,
      ISIS 2922, were studied in cynomolgus monkeys. Vitreal and retinal concentrations
      were measured after administration of 11, 57, or 115 microg/eye. ISIS 2922
      concentrations in vitreous and retina were compared, after single, weekly, or
      biweekly doses, for potential accumulation. ISIS 2922 levels were quantified
      using solid-phase extraction followed by capillary gel electrophoresis.
      Concentrations of ISIS 2922 in the vitreous were proportional to the dose and
      were nearly linear with respect to the dose. The ISIS 2922 concentrations 3 days
      after dosing ranged from 80 nM to approximately 1.5 microM. By 14 days after
      intravitreal injection, the concentrations were below the limit of quantitation
      (<10 nM) for all dose groups. There was no accumulation in the vitreous after
      multiple weekly or biweekly doses. The concentrations of ISIS 2922 in the retina
      2 days after a single intravitreal injection ranged from 50 nM to 1.1 microM. The
      uptake and disposition of ISIS 2922 in the retina appeared to have been saturated
      between the 57- and 115-microg doses; the average concentrations were 0.71 +/-
      0.24 microM (N = 4) and 0.88 +/- 0.27 microM (N = 3) for the two doses,
      respectively. Electrophoretic profiles of extracts revealed multiple chain
      shortened oligonucleotides in the vitreous and retina, suggesting extensive
      metabolism in both compartments. Analyses from the multiple-dose study suggested
      that accumulation was dependent on the total administered dose, with accumulation
      occurring after biweekly dosing in the 115-microg dose group and only after
      weekly dosing in the 57-microg dose group.

PMID- 9660850
TI  - Oxidation of a metabolite of indomethacin (Desmethyldeschlorobenzoylindomethacin)
      to reactive intermediates by activated neutrophils, hypochlorous acid, and the
      myeloperoxidase system.
AB  - The use of indomethacin is associated with a relatively high incidence of adverse
      reactions such as agranulocytosis. Many other drugs associated with
      agranulocytosis are metabolized to reactive metabolites by activated neutrophils.
      Therefore, we studied the oxidation of indomethacin and its metabolites by
      activated neutrophils, myeloperoxidase (MPO) (the major oxidizing enzyme in
      neutrophils), and HOCl (the major oxidant produced by activated neutrophils). No
      oxidation of indomethacin by activated neutrophils was observed. However,
      desmethyldeschlorobenzoylindomethacin (DMBI), a major metabolite of indomethacin,
      was oxidized to a reactive iminoquinone that could be trapped with glutathione
      (GSH) or N-acetylcysteine (NAC) to form conjugates, with MH+ ions at m/z 511 and
      367, respectively. No metabolism was detected in neutrophils that had not been
      activated, and the oxidation was inhibited by azide (which inhibits MPO) and by
      catalase (which catalyzes the breakdown of H2O2). In reactions with HOCl, the
      same reactive intermediate was formed; its mass spectrum, with a MH+ ion at m/z
      204, was obtained by using a flow system in which the reactants were fed into a
      mixing chamber and the products flowed directly into the mass spectrometer. The
      same GSH and NAC conjugates were also observed when DMBI was oxidized by HOCl or
      by the MPO system, followed by addition of GSH or NAC. NMR data for the NAC
      conjugate indicated that the sulfur was substituted in the 4-position on the
      aromatic ring. The reactive intermediate generated from DMBI by activated
      neutrophils may be responsible for indomethacin-induced agranulocytosis.

PMID- 9660851
TI  - Enantioselective, mechanism-based inactivation of guinea pig hepatic cytochrome
      P450 by N-(alpha-methylbenzyl)-1-aminobenzotriazole.
AB  - N-Aralkylated derivatives of 1-aminobenzotriazole are well-established, mechanism
      based inhibitors of cytochrome P450 (CYP or P450). In this study, the kinetics of
      inactivation of CYP2B-dependent 7-pentoxyresorufin O-depentylation (PROD) and
      CYP1A-dependent 7-ethoxyresorufin O-deethylation (EROD) activities by enantiomers
      of N-(alpha-methylbenzyl)-1-aminobenzotriazole (alphaMB) were compared. The
      racemic mixture (+/-)-alphaMB, as well as the enantiomers (-)-alphaMB and (+)
      alphaMB, produced a time-, concentration-, and NADPH-dependent loss of PROD and
      EROD activity in hepatic microsomes from phenobarbital-treated guinea pigs. The
      rates of PROD inactivation by (-)-alphaMB were significantly faster than for (+)
      alphaMB. Consistent with this, the derived maximal kinact was also significantly
      greater for (-)-alphaMB than for (+)-alphaMB (0.49 vs. 0.35 min-1). In contrast,
      the concentrations required for the half-maximal rate of inactivation (Ki) were
      equivalent for (-)-alphaMB and (+)-alphaMB, whereas the degree of competitive
      inhibition of PROD activity was greater for (+)-alphaMB. No significant
      differences were found among (-)-alphaMB, (+)-alphaMB, and (+/-)-alphaMB with
      respect to mechanism-based inactivation (kinact = 0.18, 0.16, and 0.17 min-1,
      respectively) or competitive inhibition of EROD activity. No differences were
      found for the maximal extent of PROD or EROD inhibition or the loss of spectral
      P450 after an extended 30-min incubation with the inhibitors. We conclude that
      mechanism-based inactivation of guinea pig CYP2B, but not CYP1A, isozymes by
      alphaMB occurs in a stereoselective manner, most likely as a result of a
      difference in the balance between metabolic activation and deactivation for the
      alphaMB enantiomers.

PMID- 9660852
TI  - Fentanyl in hair. Chemical factors involved in accumulation and retention of
      fentanyl in hair after external exposure or in vivo deposition.
AB  - The levels of fentanyl extractable from mouse hair after chronic systemic
      administration and the suitability of externally loaded hair samples for
      establishing control and comparison samples were determined. Additionally, the
      effects of chemical modification of specific polar functionalities within the
      hair protein matrix on the deposition and recovery of fentanyl in hair subjected
      to external loading were determined. BALB/c mice entering a second phase of
      synchronized hair growth were treated ip with fentanyl (0.02, 0.05, or 0.10
      mg/kg) on Monday, Wednesday, and Friday for 3 weeks. At that time, fentanyl
      concentrations in hair, as determined by GC/MS, were 0.025-0.050 ng/mg of hair.
      Hair samples exposed to fentanyl in phosphate buffer (ionized drug) showed no
      significant accumulation of drug into the hair, as determined by loss of fentanyl
      from the loading solution or by extraction of the hair. Hair samples exposed to
      nonionized fentanyl in methanolic solution (10, 50, and 100 ng/ml) showed
      significant accumulation of drug in the hair and significant removal of drug from
      the incubation solution. Fentanyl removal from solution plateaued after 24 hr,
      suggesting equilibration between fentanyl in solution and fentanyl in the hair. A
      mass balance between drug lost from the incubation solution and drug recovered
      from hair samples suggests that 94% of accumulated fentanyl is tightly bound to
      the hair matrix or resides in water-inaccessible compartments within the hair.
      These results suggest that fentanyl accumulation after in vivo administration
      differs, in the nature of storage, from fentanyl accumulation from external
      solutions and that external spiking of hair may not provide suitable control
      samples. Chemical modification of hair protein functionalities (reaction with
      diazomethane to esterify carboxylic acid groups or with acetic anhydride and
      pyridine to acetylate amine and hydroxyl functionalities) led to reproducible
      protein structure modification, as demonstrated by Fourier transform-IR and by pH
      titration. Hair from BALB/c mice was used. The accumulation of fentanyl was
      examined in hair samples exposed to fentanyl in methanol or methylene chloride
      solutions (10 ng/ml, 24 hr). Fentanyl was recovered from hair by 24-hr extraction
      in phosphate buffer, pH 6. Esterification of hair resulted in significantly less
      uptake of nonionized fentanyl from a methanolic solution and significantly lower
      recovery of drug from hair, relative to untreated hair, suggesting that
      carboxylic acid functionalities are necessary for the incorporation of drug.
      Acetylation of hair resulted in increased removal of fentanyl from methylene
      chloride solutions and increased recovery of fentanyl. This is consistent with
      the creation or expansion of a less polar compartment. Fentanyl uptake from a
      methanolic solution was also greater in acetylated hair. These results
      demonstrate that solution-accessible ionizable functionalities of hair play a
      significant role in the accumulation and retention of nonionized fentanyl from
      organic solutions.

PMID- 9660853
TI  - (R)-(+)-Menthofuran is a potent, mechanism-based inactivator of human liver
      cytochrome P450 2A6.
AB  - (R)-(+)-Menthofuran is a potent, mechanism-based inactivator of human liver
      cytochrome P450 (CYP or P450) 2A6. Menthofuran caused a time- and concentration
      dependent loss of CYP2A6 activity. The inactivation of CYP2A6 was characterized
      by a Ki of 2.5 microM and a kinact of 0.22 min-1 for human liver microsomes and a
      Ki of 0.84 microM and a kinact of 0.25 min-1 for purified expressed CYP2A6.
      Addition of various nucleophiles, a chelator of iron, or scavengers of reactive
      oxygen species or extensive dialysis failed to protect CYP2A6 from inactivation.
      An antibody to metallothionein conjugates of a suspected reactive metabolite of
      menthofuran was used to detect reactive menthofuran metabolite adducts with
      CYP2A6. These adducts were formed only in the presence of NADPH-P450 reductase
      and NADPH. Glutathione, methoxylamine, and semicarbazide did not prevent
      adduction of reactive menthofuran metabolites to CYP2A6, however. The menthofuran
      metabolite formation/CYP2A6 inactivation partition ratio was determined to be 3.5
      +/- 0.6 nmol/nmol of P450. Menthofuran was unable to inactivate CYP1A2, CYP2D6,
      CYP2E1, or CYP3A4 in a time- and concentration-dependent manner.

PMID- 9660854
TI  - Biotransformation of nitroso aromatic compounds and 2-oxo acids to N-hydroxy-N
      arylacylamides by thiamine-dependent enzymes in rat liver.
AB  - The formation of N-hydroxy-N-arylacylamides from nitroso aromatic compounds and 2
      oxo acids was investigated using rat liver subcellular fractions. Activities were
      found in both mitochondria and cytosol, except for activities for phenylpyruvate
      and glyoxylate; the former did not produce N-hydroxy-N-phenylphenylacetamide and
      the latter nonenzymatically produced N-hydroxy-N-phenylformamide with
      nitrosobenzene (NOB). The cytosolic activity of N-hydroxy-N-phenylglycolamide
      formation was indicated to be due to transketolase, which utilized
      hydroxypyruvate as a glycolic aldehyde donor to NOB. With mitochondria, 2-oxo
      acids (including hydroxypyruvate) served as substrates for the biotransformation
      of NOB to the corresponding N-hydroxy-N-phenylacylamides. The substrate
      preference was 2-oxobutyrate > pyruvate > 2-oxoisovalerate > 2-oxoisocaproate > 2
      oxovalerate > 2-oxo-3-methylvalerate, judging from Vmax/half-saturating
      concentration for mitochondria values. The half-saturating concentrations for NOB
      were nearly constant. The mitochondrial activity was due to pyruvate
      dehydrogenase complex and branched-chain 2-oxo acid dehydrogenase complex
      (BCDHC). By using partially purified BCDHC, pyruvate and 2-oxobutyrate were found
      to be common substrates for both of the enzymes, and 2-oxoisovalerate was shown
      to be the most effective substrate for BCDHC. Analysis by the Taft equation
      indicated that the polar effects, rather than the steric effects, of the alkyl
      groups of 2-oxo acids are important for BCDHC-catalyzed formation of N-hydroxy-N
      phenylacylamides. A positive Hammett constant obtained for the formation of N
      hydroxy-N-arylisobutyramides indicates that an electron-withdrawing substituent
      makes the nitroso compounds susceptible to BCDHC-catalyzed biotransformation.

PMID- 9660855
TI  - Metabolism of 1,1-dichloro-1-fluoroethane (HCFC-141b) in human volunteers.
AB  - Human subjects were exposed by inhalation to 250, 500, and 1000 ppm 1,1-dichloro
      1-fluoroethane (HCFC-141b) for 4 hr, and urine samples were collected from 0-4, 4
      12, and 12-24 hr for metabolite analysis. 19F nuclear magnetic resonance
      spectroscopic analysis of urine samples from exposed subjects showed that 2,2
      dichloro-2-fluoroethyl glucuronide and dichlorofluoroacetic acid were the major
      and minor metabolites, respectively, of HCFC-141b. Urinary 2, 2-dichloro-2
      fluoroethyl glucuronide was hydrolyzed to 2, 2-dichloro-2-fluoroethanol by
      incubation with beta-glucuronidase, and the released 2,2-dichloro-2-fluoroethanol
      was quantified by gas chromatography/mass spectrometry. Concentrations of 2, 2
      dichloro-2-fluoroethanol were highest in the urine samples collected 4-12 hr
      after exposure, but 2,2-dichloro-2-fluoroethanol was also detected in the samples
      collected 0-4 and 12-24 hr after exposure. Exposure concentration-dependent
      excretion of 2, 2-dichloro-2-fluoroethanol, obtained by hydrolysis of 2, 2
      dichloro-2-fluoroethyl glucuronide, was observed in seven of the eight subjects
      studied. In conclusion, HCFC-141b is metabolized in human subjects to 2,2
      dichloro-2-fluoroethanol, which is conjugated with glucuronic acid and excreted
      as its glucuronide in urine in a time- and exposure concentration-dependent
      manner.

PMID- 9660856
TI  - Effects of age, sex, and pharmacologic agents on the biliary elimination of
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in F344 rats.
AB  - The extreme biological persistence of 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD)
      is due primarily to its resistance to metabolic transformation. Previous studies
      in several species have found hepatic metabolism to be rate-limiting for TCDD
      elimination, with resulting metabolites excreted primarily in feces via the bile.
      Using short-term biliary excretion of [3H]TCDD metabolites as an indirect measure
      of metabolism, groups of F344 rats were used to evaluate separately the effects
      of age, sex, and acute induction or inhibition of key hepatic enzymes. Adult and
      juvenile male and female rats were used for sex comparisons, and senescent male
      rats were used to explore possible changes in TCDD metabolism with age. Various
      pretreatments were used: phenobarbital (PB) and dexamethasone (DEX), to induce
      hepatic cytochrome P450 isozymes; and suicide substrate 1-aminobenzotriazole
      (ABT), to produce P450 inhibition. For all animals, surgical cannulation of the
      common bile duct and 6-hr bile collection were performed under constant
      anesthesia. [3H]TCDD (1 nmol/kg) was administered via the femoral vein. Naive
      adult male and female rats excreted approximately 0.7% and approximately 0.4% of
      [3H]TCDD-derived radioactivity, respectively. Biliary excretion of radioactivity
      in both male and female juvenile rats was similar to that of adult males;
      senescent male rats excreted less. Pretreatment with PB, DEX, or ABT resulted in
      similar decrease in biliary excretion of TCDD-derived radioactivity as observed
      in senescent male rats.

PMID- 9660857
TI  - Isolation and identification of bromfenac glucoside from rat bile.
AB  - Bromfenac (Duract(R)), a drug approved for pain, was expected to be metabolized
      by the rat to an acyl glucuronide, a metabolite formed with most compounds of
      similar structure. During the investigation of metabolite profiles in rat bile
      following administration of 1 mg/kg iv doses of 14C-bromfenac, an acid-labile
      metabolite was found that degraded to form 14C-bromfenac. Isolation and
      characterization of this metabolite indicated that it is an unusual conjugate,
      bromfenac N-glucoside.

PMID- 9660858
TI  - The human homologue of Bub3 is required for kinetochore localization of Bub1 and
      a Mad3/Bub1-related protein kinase.
AB  - A feedback control mechanism, or cell cycle checkpoint, delays the onset of
      anaphase until all the chromosomes are correctly aligned on the mitotic spindle.
      Previously, we showed that the murine homologue of Bub1 is not only required for
      checkpoint response to spindle damage, but also restrains progression through a
      normal mitosis (Taylor, S.S., and F. McKeon. 1997. Cell. 89:727-735). Here, we
      describe the identification of a human homologue of Bub3, a 37-kD protein with
      four WD repeats. Like Bub1, Bub3 localizes to kinetochores before chromosome
      alignment. In addition, Bub3 and Bub1 interact in mammalian cells. Deletion
      mapping was used to identify the domain of Bub1 required for binding Bub3.
      Significantly, this same domain is required for kinetochore localization of Bub1,
      suggesting that the role of Bub3 is to localize Bub1 to the kinetochore, thereby
      activating the checkpoint in response to unattached kinetochores. The
      identification of a human Mad3/Bub1-related protein kinase, hBubR1, which can
      also bind Bub3 in mammalian cells, is described. Ectopically expressed hBubR1
      also localizes to kinetochores during prometaphase, but only when hBub3 is
      overexpressed. We discuss the implications of the common interaction between Bub1
      and hBubR1 with hBub3 for checkpoint control.

PMID- 9660859
TI  - Stabilization and localization of Xist RNA are controlled by separate mechanisms
      and are not sufficient for X inactivation.
AB  - These studies address whether XIST RNA is properly localized to the X chromosome
      in somatic cells where human XIST expression is reactivated, but fails to result
      in X inactivation (Tinker, A.V., and C.J. Brown. 1998. Nucl. Acids Res. 26:2935
      2940). Despite a nuclear RNA accumulation of normal abundance and stability, XIST
      RNA does not localize in reactivants or in naturally inactive human X chromosomes
      in mouse/ human hybrid cells. The XIST transcripts are fully stabilized despite
      their inability to localize, and hence XIST RNA localization can be uncoupled
      from stabilization, indicating that these are separate steps controlled by
      distinct mechanisms. Mouse Xist RNA tightly localized to an active X chromosome,
      demonstrating for the first time that the active X chromosome in somatic cells is
      competent to associate with Xist RNA. These results imply that species-specific
      factors, present even in mature, somatic cells that do not normally express Xist,
      are necessary for localization. When Xist RNA is properly localized to an active
      mouse X chromosome, X inactivation does not result. Therefore, there is not a
      strict correlation between Xist localization and chromatin inactivation.
      Moreover, expression, stabilization, and localization of Xist RNA are not
      sufficient for X inactivation. We hypothesize that chromosomal association of
      XIST RNA may initiate subsequent developmental events required to enact
      transcriptional silencing.

PMID- 9660860
TI  - PDMP blocks brefeldin A-induced retrograde membrane transport from golgi to ER:
      evidence for involvement of calcium homeostasis and dissociation from
      sphingolipid metabolism.
AB  - In this study, we show that an inhibitor of sphingolipid biosynthesis, D,L-threo
      1-phenyl-2- decanoylamino-3-morpholino-1-propanol (PDMP), inhibits brefeldin A
      (BFA)-induced retrograde membrane transport from Golgi to endoplasmic reticulum
      (ER). If BFA treatment was combined with or preceded by PDMP administration to
      cells, disappearance of discrete Golgi structures did not occur. However, when
      BFA was allowed to exert its effect before PDMP addition, PDMP could not "rescue"
      the Golgi compartment. Evidence is presented showing that this action of PDMP is
      indirect, which means that the direct target is not sphingolipid metabolism at
      the Golgi apparatus. A fluorescent analogue of PDMP, 6-(N-[7-nitro-2,1, 3
      benzoxadiazol-4-yl]amino)hexanoyl-PDMP (C6-NBD-PDMP), did not localize in the
      Golgi apparatus. Moreover, the effect of PDMP on membrane flow did not correlate
      with impaired C6-NBD-sphingomyelin biosynthesis and was not mimicked by exogenous
      C6-ceramide addition or counteracted by exogenous C6-glucosylceramide addition.
      On the other hand, the PDMP effect was mimicked by the multidrug resistance
      protein inhibitor MK571. The effect of PDMP on membrane transport correlated with
      modulation of calcium homeostasis, which occurred in a similar concentration
      range. PDMP released calcium from at least two independent calcium stores and
      blocked calcium influx induced by either extracellular ATP or thapsigargin. Thus,
      the biological effects of PDMP revealed a relation between three important
      physiological processes of multidrug resistance, calcium homeostasis, and
      membrane flow in the ER/ Golgi system.

PMID- 9660861
TI  - Assembly of the yeast vacuolar H+-ATPase occurs in the endoplasmic reticulum and
      requires a Vma12p/Vma22p assembly complex.
AB  - Three previously identified genes from Saccharomyces cerevisiae, VMA12, VMA21,
      and VMA22, encode proteins localized to the endoplasmic reticulum (ER). These
      three proteins are required for the biogenesis of a functional vacuolar ATPase (V
      ATPase), but are not part of the final enzyme complex. Subcellular fractionation
      and chemical cross-linking studies have revealed that Vma12p and Vma22p form a
      stable membrane associated complex. Cross-linking analysis also revealed a direct
      physical interaction between the Vma12p/Vma22p assembly complex and Vph1p, the
      100-kD integral membrane subunit of the V-ATPase. The interaction of the
      Vma12p/Vma22p complex with Vph1p was transient (half-life of approximately 5
      min), reflecting trafficking of this V-ATPase subunit through the ER en route to
      the vacuolar membrane. Analysis of these protein-protein interactions in ER
      blocked sec12 mutant cells indicated that the Vph1p-Vma12p/Vma22p interactions
      are quite stable when transport of the V-ATPase out of the ER is blocked.
      Fractionation of solubilized membrane proteins on a density gradient revealed
      comigration of Vma22p and Vma12p, indicating that they form a complex even in the
      absence of cross-linker. Vma12p and Vma22p migrated to fractions separate from
      Vma21p. Loss of Vph1p caused the Vma12p/Vma22p complex to sediment to less dense
      fractions, consistent with association of Vma12p/ Vma22p with nascent Vph1p in ER
      membranes. This is the first evidence for a dedicated assembly complex in the ER
      required for the assembly of an integral membrane protein complex (V-ATPase) as
      it is transported through the secretory pathway.

PMID- 9660862
TI  - Mutations in the middle of the transmembrane domain reverse the polarity of
      transport of the influenza virus hemagglutinin in MDCK epithelial cells.
AB  - The composition of the plasma membrane domains of epithelial cells is maintained
      by biosynthetic pathways that can sort both proteins and lipids into transport
      vesicles destined for either the apical or basolateral surface. In MDCK cells,
      the influenza virus hemagglutinin is sorted in the trans-Golgi network into
      detergent-insoluble, glycosphingolipid-enriched membrane domains that are
      proposed to be necessary for sorting hemagglutinin to the apical cell surface.
      Site- directed mutagenesis of the hemagglutinin transmembrane domain was used to
      test this proposal. The region of the transmembrane domain required for apical
      transport included the residues most conserved among hemagglutinin subtypes.
      Several mutants were found to enter detergent-insoluble membranes but were not
      properly sorted. Replacement of transmembrane residues 520 and 521 with alanines
      converted the 2A520 mutant hemagglutinin into a basolateral protein. Depleting
      cell cholesterol reduced the ability of wild-type hemagglutinin to partition into
      detergent-insoluble membranes but had no effect on apical or basolateral sorting.
      In contrast, cholesterol depletion allowed random transport of the 2A520 mutant.
      The mutant appeared to lack sorting information but was prevented from reaching
      the apical surface when detergent-insoluble membranes were present. Apical
      sorting of hemagglutinin may require binding of either protein or lipids at the
      middle of the transmembrane domain and this normally occurs in detergent
      insoluble membrane domains. Entry into these domains appears necessary, but not
      sufficient, for apical sorting.

PMID- 9660863
TI  - The LDL receptor clustering motif interacts with the clathrin terminal domain in
      a reverse turn conformation.
AB  - Previously the hexapeptide motif FXNPXY807 in the cytoplasmic tail of the LDL
      receptor was shown to be essential for clustering in clathrin-coated pits. We
      used nuclear magnetic resonance line-broadening and transferred nuclear
      Overhauser effect measurements to identify the molecule in the clathrin lattice
      that interacts with this hexapeptide, and determined the structure of the bound
      motif. The wild-type peptide bound in a single conformation with a reverse turn
      at residues NPVY. Tyr807Ser, a peptide that harbors a mutation that disrupts
      receptor clustering, displayed markedly reduced interactions. Clustering motif
      peptides interacted with clathrin cages assembled in the presence or absence of
      AP2, with recombinant clathrin terminal domains, but not with clathrin hubs. The
      identification of terminal domains as the primary site of interaction for
      FXNPXY807 suggests that adaptor molecules are not required for receptor-mediated
      endocytosis of LDL, and that at least two different tyrosine-based
      internalization motifs exist for clustering receptors in coated pits.

PMID- 9660864
TI  - Distribution of a glycosylphosphatidylinositol-anchored protein at the apical
      surface of MDCK cells examined at a resolution of <100 A using imaging
      fluorescence resonance energy transfer.
AB  - Membrane microdomains ("lipid rafts") enriched in glycosylphosphatidylinositol
      (GPI)-anchored proteins, glycosphingolipids, and cholesterol have been implicated
      in events ranging from membrane trafficking to signal transduction. Although
      there is biochemical evidence for such membrane microdomains, they have not been
      visualized by light or electron microscopy. To probe for microdomains enriched in
      GPI- anchored proteins in intact cell membranes, we used a novel form of digital
      microscopy, imaging fluorescence resonance energy transfer (FRET), which extends
      the resolution of fluorescence microscopy to the molecular level (<100 A). We
      detected significant energy transfer between donor- and acceptor-labeled
      antibodies against the GPI-anchored protein 5' nucleotidase (5' NT) at the apical
      membrane of MDCK cells. The efficiency of energy transfer correlated strongly
      with the surface density of the acceptor-labeled antibody. The FRET data
      conformed to theoretical predictions for two-dimensional FRET between randomly
      distributed molecules and were inconsistent with a model in which 5' NT is
      constitutively clustered. Though we cannot completely exclude the possibility
      that some 5' NT is in clusters, the data imply that most 5' NT molecules are
      randomly distributed across the apical surface of MDCK cells. These findings
      constrain current models for lipid rafts and the membrane organization of GPI
      anchored proteins.

PMID- 9660865
TI  - Effects of regulated expression of mutant RhoA and Rac1 small GTPases on the
      development of epithelial (MDCK) cell polarity.
AB  - MDCK cells expressing RhoA or Rac1 mutants under control of the tetracycline
      repressible transactivator were used to examine short-term effects of known
      amounts of each mutant before, during, or after development of cell polarity. At
      low cell density, Rac1V12 cells had a flattened morphology and intact cell-cell
      contacts, whereas Rac1N17 cells were tightly compacted. Abnormal intracellular
      aggregates formed between Rac1N17, F-actin, and E-cadherin in these nonpolarized
      cells. At all subsequent stages of polarity development, Rac1N17 and Rac1V12
      colocalized with E-cadherin and F-actin in an unusual beaded pattern at lateral
      membranes. In polarized cells, intracellular aggregates formed with Rac1V12, F
      actin, and an apical membrane protein (GP135). At low cell density, RhoAV14 and
      RhoAN19 were localized in the cytoplasm, and cells were generally flattened and
      more fibroblastic than epithelial in morphology. In polarized RhoAV14 cells, F
      actin was diffuse at lateral membranes and prominent in stress fibers on the
      basal membrane. GP135 was abnormally localized to the lateral membrane and in
      intracellular aggregates, but E-cadherin distribution appeared normal. In RhoAN19
      cells, F-actin, E-cadherin, and GP135 distributions were similar to those in
      controls. Expression of either RhoAV14 or RhoAN19 in Rac1V12 cells disrupted
      Rac1V12 distribution and caused cells to adopt the more fibroblastic, RhoA mutant
      phenotype. We suggest that Rac1 and RhoA are involved in the transition of
      epithelial cells from a fibroblastic to a polarized structure and function by
      direct and indirect regulation of actin and actin-associated membrane protein
      organizations.

PMID- 9660866
TI  - Structural and functional regulation of tight junctions by RhoA and Rac1 small
      GTPases.
AB  - Tight junctions (TJ) govern ion and solute diffusion through the paracellular
      space (gate function), and restrict mixing of membrane proteins and lipids
      between membrane domains (fence function) of polarized epithelial cells. We
      examined roles of the RhoA and Rac1 GTPases in regulating TJ structure and
      function in MDCK cells using the tetracycline repressible transactivator to
      regulate RhoAV14, RhoAN19, Rac1V12, and Rac1N17 expression. Both constitutively
      active and dominant negative RhoA or Rac1 perturbed TJ gate function
      (transepithelial electrical resistance, tracer diffusion) in a dose-dependent and
      reversible manner. Freeze-fracture EM and immunofluoresence microscopy revealed
      abnormal TJ strand morphology and protein (occludin, ZO-1) localization in
      RhoAV14 and Rac1V12 cells. However, TJ strand morphology and protein localization
      appeared normal in RhoAN19 and Rac1N17 cells. All mutant GTPases disrupted the
      fence function of the TJ (interdomain diffusion of a fluorescent lipid), but
      targeting and organization of a membrane protein in the apical membrane were
      unaffected. Expression levels and protein complexes of occludin and ZO-1 appeared
      normal in all mutant cells, although ZO-1 was more readily solubilized from
      RhoAV14-expressing cells with Triton X-100. These results show that RhoA and Rac1
      regulate gate and fence functions of the TJ, and play a role in the spatial
      organization of TJ proteins at the apex of the lateral membrane.

PMID- 9660867
TI  - Junctional adhesion molecule, a novel member of the immunoglobulin superfamily
      that distributes at intercellular junctions and modulates monocyte
      transmigration.
AB  - Tight junctions are the most apical components of endothelial and epithelial
      intercellular cleft. In the endothelium these structures play an important role
      in the control of paracellular permeability to circulating cells and solutes. The
      only known integral membrane protein localized at sites of membrane-membrane
      interaction of tight junctions is occludin, which is linked inside the cells to a
      complex network of cytoskeletal and signaling proteins. We report here the
      identification of a novel protein (junctional adhesion molecule [JAM]) that is
      selectively concentrated at intercellular junctions of endothelial and epithelial
      cells of different origins. Confocal and immunoelectron microscopy shows that JAM
      codistributes with tight junction components at the apical region of the
      intercellular cleft. A cDNA clone encoding JAM defines a novel immunoglobulin
      gene superfamily member that consists of two V-type Ig domains. An mAb directed
      to JAM (BV11) was found to inhibit spontaneous and chemokine-induced monocyte
      transmigration through an endothelial cell monolayer in vitro. Systemic treatment
      of mice with BV11 mAb blocked monocyte infiltration upon chemokine administration
      in subcutaneous air pouches. Thus, JAM is a new component of endothelial and
      epithelial junctions that play a role in regulating monocyte transmigration.

PMID- 9660868
TI  - Human CASK/LIN-2 binds syndecan-2 and protein 4.1 and localizes to the
      basolateral membrane of epithelial cells.
AB  - In Caenorhabditis elegans, mutations in the lin-2 gene inactivate the LET-23
      receptor tyrosine kinase/Ras/MAP kinase pathway required for vulval cell
      differentiation. One function of LIN-2 is to localize LET-23 to the basal
      membrane domain of vulval precursor cells. LIN-2 belongs to the membrane
      associated guanylate kinase family of proteins. We have cloned and characterized
      the human homolog of LIN-2, termed hCASK, and Northern and Western blot analyses
      reveal that it is ubiquitously expressed. Indirect immunofluorescence localizes
      CASK to distinct lateral and/or basal plasma membrane domains in different
      epithelial cell types. We detect in a yeast two-hybrid screen that the PDZ domain
      of hCASK binds to the heparan sulfate proteoglycan syndecan-2. This interaction
      is confirmed using in vitro binding assays and immunofluorescent colocalization.
      Furthermore, we demonstrate that hCASK binds the actin-binding protein 4.1.
      Syndecans are known to bind extracellular matrix, and to form coreceptor
      complexes with receptor tyrosine kinases. We speculate that CASK mediates a link
      between the extracellular matrix and the actin cytoskeleton via its interaction
      with syndecan and with protein 4.1. Like other membrane-associated guanylate
      kinases, its multidomain structure enables it to act as a scaffold at the
      membrane, potentially recruiting multiple proteins and coordinating signal
      transduction.

PMID- 9660869
TI  - Direct interaction of CASK/LIN-2 and syndecan heparan sulfate proteoglycan and
      their overlapping distribution in neuronal synapses.
AB  - CASK, the rat homolog of a gene (LIN-2) required for vulval differentiation in
      Caenorhabditis elegans, is expressed in mammalian brain, but its function in
      neurons is unknown. CASK is distributed in a punctate somatodendritic pattern in
      neurons. By immunogold EM, CASK protein is concentrated in synapses, but is also
      present at nonsynaptic membranes and in intracellular compartments. This
      immunolocalization is consistent with biochemical studies showing the presence of
      CASK in soluble and synaptosomal membrane fractions and its enrichment in
      postsynaptic density fractions of rat brain. By yeast two-hybrid screening, a
      specific interaction was identified between the PDZ domain of CASK and the COOH
      terminal tail of syndecan-2, a cell surface heparan sulfate proteoglycan (HSPG).
      The interaction was confirmed by coimmunoprecipitation from heterologous cells.
      In brain, syndecan-2 localizes specifically at synaptic junctions where it shows
      overlapping distribution with CASK, consistent with an interaction between these
      proteins in synapses. Cell surface HSPGs can bind to extracellular matrix
      proteins, and are required for the action of various heparin-binding polypeptide
      growth/differentiation factors. The synaptic localization of CASK and syndecan
      suggests a potential role for these proteins in adhesion and signaling at
      neuronal synapses.

PMID- 9660870
TI  - Functional specialization of stable and dynamic microtubules in protein traffic
      in WIF-B cells.
AB  - We found that the magnesium salt of ilimaquinone, named 201-F, specifically
      disassembled dynamically unstable microtubules in fibroblasts and various
      epithelial cell lines. Unlike classical tubulin- interacting drugs such as
      nocodazole or colchicine which affect all classes of microtubules, 201-F did not
      depolymerize stable microtubules. In WIF-B-polarized hepatic cells, 201-F
      disrupted the Golgi complex and inhibited albumin and alpha1-antitrypsin
      secretion to the same extent as nocodazole. By contrast, 201-F did not impair the
      transport of membrane proteins to the basolateral surface, which was only
      affected by the total disassembly of cellular microtubules. Transcytosis of two
      apical membrane proteins-the alkaline phosphodiesterase B10 and dipeptidyl
      peptidase IV-was affected to the same extent by 201-F and nocodazole. Taken
      together, these results indicate that only dynamically unstable microtubules are
      involved in the transport of secretory proteins to the plasma membrane, and in
      the transcytosis of membrane proteins to the apical surface. By contrast, stable
      microtubules, which are not functionally affected by 201-F treatment, are
      involved in the transport of membrane proteins to the basolateral surface. By
      specifically disassembling highly dynamic microtubules, 201-F is an invaluable
      tool with which to study the functional specialization of stable and dynamic
      microtubules in living cells.

PMID- 9660871
TI  - STOP proteins are responsible for the high degree of microtubule stabilization
      observed in neuronal cells.
AB  - Neuronal differentiation and function require extensive stabilization of the
      microtubule cytoskeleton. Neurons contain a large proportion of microtubules that
      resist the cold and depolymerizing drugs and exhibit slow subunit turnover. The
      origin of this stabilization is unclear. Here we have examined the role of STOP,
      a calmodulin-regulated protein previously isolated from cold-stable brain
      microtubules. We find that neuronal cells express increasing levels of STOP and
      of STOP variants during differentiation. These STOP proteins are associated with
      a large proportion of microtubules in neuronal cells, and are concentrated on
      cold-stable, drug-resistant, and long-lived polymers. STOP inhibition abolishes
      microtubule cold and drug stability in established neurites and impairs neurite
      formation. Thus, STOP proteins are responsible for microtubule stabilization in
      neurons, and are apparently required for normal neurite formation.

PMID- 9660872
TI  - Targeting, capture, and stabilization of microtubules at early focal adhesions.
AB  - By co-injecting fluorescent tubulin and vinculin into fish fibroblasts we have
      revealed a "cross talk" between microtubules and early sites of substrate
      contact. This mutuality was first indicated by the targeting of vinculin-rich
      foci by microtubules during their growth towards the cell periphery. In addition
      to passing directly over contact sites, the ends of single microtubules could be
      observed to target several contacts in succession or the same contact
      repetitively, with intermittent withdrawals. Targeting sometimes involved side
      stepping, or the major re-routing of a microtubule, indicative of a guided,
      rather than a random process. The paths that microtubules followed into contacts
      were unrelated to the orientation of stress fiber assemblies and targeting
      occurred also in mouse fibroblasts that lacked a system of intermediate
      filaments. Further experiments with microtubule inhibitors showed that adhesion
      foci can: (a) capture microtubules and stabilize them against disassembly by
      nocodazole; and (b), act as preferred sites of microtubule polymerization, during
      either early recovery from nocodazole, or brief treatment with taxol. From these
      and other findings we speculate that microtubules are guided into substrate
      contact sites and through the motor-dependent delivery of signaling molecules
      serve to modulate their development. It is further proposed this modulation
      provides the route whereby microtubules exert their influence on cell shape and
      polarity.

PMID- 9660873
TI  - Unique responses of differentiating neuronal growth cones to inhibitory cues
      presented by oligodendrocytes.
AB  - During central nervous system development, neurons differentiate distinct axonal
      and dendritic processes whose outgrowth is influenced by environmental cues.
      Given the known intrinsic differences between axons and dendrites and that little
      is known about the response of dendrites to inhibitory cues, we tested the
      hypothesis that outgrowth of differentiating axons and dendrites of hippocampal
      neurons is differentially influenced by inhibitory environmental cues. A
      sensitive growth cone behavior assay was used to assess responses of
      differentiating axonal and dendritic growth cones to oligodendrocytes and
      oligodendrocyte- derived, myelin-associated glycoprotein (MAG). We report that
      >90% of axonal growth cones collapsed after contact with oligodendrocytes. None
      of the encounters between differentiating, MAP-2 positive dendritic growth cones
      and oligodendrocytes resulted in growth cone collapse. The insensitivity of
      differentiating dendritic growth cones appears to be acquired since they develop
      from minor processes whose growth cones are inhibited (nearly 70% collapse) by
      contact with oligodendrocytes. Recombinant MAG(rMAG)-coated beads caused collapse
      of 72% of axonal growth cones but only 29% of differentiating dendritic growth
      cones. Unlike their response to contact with oligodendrocytes, few growth cones
      of minor processes were inhibited by rMAG-coated beads (20% collapsed). These
      results reveal the capability of differentiating growth cones of the same neuron
      to partition the complex molecular terrain they navigate by generating unique
      responses to particular inhibitory environmental cues.

PMID- 9660874
TI  - Involvement of receptor-like protein tyrosine phosphatase zeta/RPTPbeta and its
      ligand pleiotrophin/heparin-binding growth-associated molecule (HB-GAM) in
      neuronal migration.
AB  - Pleiotrophin/heparin-binding growth-associated molecule (HB-GAM) is a specific
      ligand of protein tyrosine phosphatase zeta (PTPzeta)/receptor-like protein
      tyrosine phosphatase beta (RPTPbeta) expressed in the brain as a chondroitin
      sulfate proteoglycan. Pleiotrophin and PTPzeta isoforms are localized along the
      radial glial fibers, a scaffold for neuronal migration, suggesting that these
      molecules are involved in migratory processes of neurons during brain
      development. In this study, we examined the roles of pleiotrophin-PTPzeta
      interaction in the neuronal migration using cell migration assay systems with
      glass fibers and Boyden chambers. Pleiotrophin and poly-L-lysine coated on the
      substratums stimulated cell migration of cortical neurons, while laminin,
      fibronectin, and tenascin exerted almost no effect. Pleiotrophin-induced and poly
      L-lysine-induced neuronal migrations showed significant differences in
      sensitivity to various molecules and reagents. Polyclonal antibodies against the
      extracellular domain of PTPzeta, PTPzeta-S, an extracellular secreted form of
      PTPzeta, and sodium vanadate, a protein tyrosine phosphatase inhibitor, added
      into the culture medium strongly suppressed specifically the pleiotrophin-induced
      neuronal migration. Furthermore, chondroitin sulfate C but not chondroitin
      sulfate A inhibited pleiotrophin-induced neuronal migration, in good accordance
      with our previous findings that chondroitin sulfate constitutes a part of the
      pleiotrophin-binding site of PTPzeta, and PTPzeta-pleiotrophin binding is
      inhibited by chondroitin sulfate C but not by chondroitin sulfate A.
      Immunocytochemical analysis indicated that the transmembrane forms of PTPzeta are
      expressed on the migrating neurons especially at the lamellipodia along the
      leading processes. These results suggest that PTPzeta is involved in the neuronal
      migration as a neuronal receptor of pleiotrophin distributed along radial glial
      fibers.

PMID- 9660875
TI  - Regulation of angiotensin II-induced neuromodulation by MARCKS in brain neurons.
AB  - Angiotensin II (Ang II) exerts chronic stimulatory actions on tyrosine
      hydroxylase (TH), dopamine beta-hydroxylase (DbetaH), and the norepinephrine
      transporter (NET), in part, by influencing the transcription of their genes.
      These neuromodulatory actions of Ang II involve Ras-Raf-MAP kinase signal
      transduction pathways (Lu, D., H. Yang, and M.K. Raizada. 1997. J. Cell Biol.
      135:1609-1617). In this study, we present evidence to demonstrate participation
      of another signaling pathway in these neuronal actions of Ang II. It involves
      activation of protein kinase C (PKC)beta subtype and phosphorylation and
      redistribution of myristoylated alanine-rich C kinase substrate (MARCKS) in
      neurites. Ang II caused a dramatic redistribution of MARCKS from neuronal
      varicosities to neurites. This was accompanied by a time-dependent stimulation of
      its phosphorylation, that was mediated by the angiotensin type 1 receptor subtype
      (AT1). Incubation of neurons with PKCbeta subtype specific antisense
      oligonucleotide (AON) significantly attenuated both redistribution and
      phosphorylation of MARCKS. Furthermore, depletion of MARCKS by MARCKS-AON
      treatment of neurons resulted in a significant decrease in Ang II-stimulated
      accumulation of TH and DbetaH immunoreactivities and [3H]NE uptake activity in
      synaptosomes. In contrast, mRNA levels of TH, DbetaH, and NET were not influenced
      by MARKS-AON treatment. MARCKS pep148-165, which contains PKC phosphorylation
      sites, inhibited Ang II stimulation of MARCKS phosphorylation and reduced the
      amount of TH, DbetaH, and [3H]NE uptake in neuronal synaptosomes. These
      observations demonstrate that phosphorylation of MARCKS by PKCbeta and its
      redistribution from varicosities to neurites is important in Ang II-induced
      synaptic accumulation of TH, DbetaH, and NE. They suggest that a coordinated
      stimulation of transcription of TH, DbetaH, and NET, mediated by Ras-Raf-MAP
      kinase followed by their transport mediated by PKCbeta-MARCKS pathway are key in
      persistent stimulation of Ang II's neuromodulatory actions.

PMID- 9660876
TI  - Dual actions of sphingosine-1-phosphate: extracellular through the Gi-coupled
      receptor Edg-1 and intracellular to regulate proliferation and survival.
AB  - Sphingosine-1-phosphate (SPP), a bioactive lipid, acts both intracellularly and
      extracellularly to cause pleiotropic biological responses. Recently, we
      identified SPP as a ligand for the G protein-coupled receptor Edg-1 (Lee, M.-J.,
      J.R. Van Brocklyn, S. Thangada, C.H. Liu, A.R. Hand, R. Menzeleev, S. Spiegel,
      and T. Hla. 1998. Science. 279:1552-1555). Edg-1 binds SPP with remarkable
      specificity as only sphinganine-1-phosphate displaced radiolabeled SPP, while
      other sphingolipids did not. Binding of SPP to Edg-1 resulted in inhibition of
      forskolin-stimulated cAMP accumulation, in a pertussis toxin-sensitive manner. In
      contrast, two well-characterized biological responses of SPP, mitogenesis and
      prevention of apoptosis, were clearly unrelated to binding to Edg-1 and
      correlated with intracellular uptake. SPP also stimulated signal transduction
      pathways, including calcium mobilization, activation of phospholipase D, and
      tyrosine phosphorylation of p125(FAK), independently of edg-1 expression.
      Moreover, DNA synthesis in Swiss 3T3 fibroblasts was significantly and
      specifically increased by microinjection of SPP. Finally, SPP suppresses
      apoptosis of HL-60 and pheochromocytoma PC12 cells, which do not have specific
      SPP binding or expression of Edg-1 mRNA. Conversely, sphinganine-1-phosphate,
      which binds to and signals via Edg-1, does not have any significant
      cytoprotective effect. Thus, SPP is a prototype for a novel class of lipid
      mediators that act both extracellularly as ligands for cell surface receptors and
      intracellularly as second messengers.

PMID- 9660877
TI  - The FGF receptor-1 tyrosine kinase domain regulates myogenesis but is not
      sufficient to stimulate proliferation.
AB  - Ligand-stimulated activation of FGF receptors (FGFRs) in skeletal muscle cells
      represses terminal myogenic differentiation. Skeletal muscle cell lines and
      subsets of primary cells are dependent on FGFs to repress myogenesis and maintain
      growth. To understand the intracellular events that transduce these signals, MM14
      skeletal muscle cells were transfected with expression vectors encoding chimeric
      receptors. The chimeras are comprised of the PDGF beta receptor (PDGFbetaR)
      extracellular domain, the FGFR-1 intracellular domain, and either the PDGFbetaR
      or FGFR-1 transmembrane domain. The chimeric receptors were autophosphorylated
      upon PDGF-BB stimulation and are capable of stimulating mitogen-activated protein
      kinase activity. Activation of the tyrosine kinase domain of either chimera
      repressed myogenesis, suggesting intracellular responses regulating skeletal
      muscle differentiation are transduced by activation of the FGFR-1 tyrosine
      kinase. Unexpectedly, we found that activation of either chimeric receptor failed
      to stimulate cellular proliferation. Thus, it appears that regulation of skeletal
      muscle differentiation by FGFs requires only activation of the FGFR tyrosine
      kinase. In contrast, stimulation of proliferation may require additional, as yet
      unidentified, signals involving the receptor ectodomain, the FGF ligand, and
      heparan sulfate either alone, or in combination.

PMID- 9660878
TI  - Structural requirements for outside-in and inside-out signaling by Drosophila
      neuroglian, a member of the L1 family of cell adhesion molecules.
AB  - Expression of the Drosophila cell adhesion molecule neuroglian in S2 cells leads
      to cell aggregation and the intracellular recruitment of ankyrin to cell contact
      sites. We localized the region of neuroglian that interacts with ankyrin and
      investigated the mechanism that limits this interaction to cell contact sites.
      Yeast two-hybrid analysis and expression of neuroglian deletion constructs in S2
      cells identified a conserved 36-amino acid sequence that is required for ankyrin
      binding. Mutation of a conserved tyrosine residue within this region reduced
      ankyrin binding and extracellular adhesion. However, residual recruitment of
      ankyrin by this mutant neuroglian molecule was still limited to cell contacts,
      indicating that the lack of ankyrin binding at noncontact sites is not caused by
      tyrosine phosphorylation. A chimeric molecule, in which the extracellular domain
      of neuroglian was replaced with the corresponding domain from the adhesion
      molecule fasciclin II, also selectively recruited ankyrin to cell contacts. Thus,
      outside-in signaling by neuroglian in S2 cells depends on extracellular adhesion,
      but does not depend on any unique property of its extracellular domain. We
      propose that the recruitment of ankyrin to cell contact sites depends on a
      physical rearrangement of neuroglian in response to cell adhesion, and that
      ankyrin binding plays a reciprocal role in stabilizing the adhesive interaction.

PMID- 9660879
TI  - Dimerization of P-selectin glycoprotein ligand-1 (PSGL-1) required for optimal
      recognition of P-selectin.
AB  - Interactions between P-selectin, expressed on endothelial cells and activated
      platelets, and its leukocyte ligand, a homodimer termed P-selectin glycoprotein
      ligand-1 (PSGL-1), mediate the earliest adhesive events during an inflammatory
      response. To investigate whether dimerization of PSGL-1 is essential for
      functional interactions with P-selectin, a mutant form of PSGL-1 was generated in
      which the conserved membrane proximal cysteine was mutated to alanine (designated
      C320A). Western blotting under both denaturing and native conditions of the C320A
      PSGL-1 mutant isolated from stably transfected cells revealed expression of only
      a monomeric form of PSGL-1. In contrast to cells cotransfected with alpha1-3
      fucosyltransferase-VII (FucT-VII) plus PSGL-1, K562 cells expressing FucT-VII
      plus C320A failed to bind COS cells transfected with P-selectin in a low shear
      adhesion assay, or to roll on CHO cells transfected with P-selectin under
      conditions of physiologic flow. In addition, C320A transfectants failed to bind
      chimeric P-selectin fusion proteins. Both PSGL-1 and C320A were uniformly
      distributed on the surface of transfected K562 cells. Thus, dimerization of PSGL
      1 through the single, conserved, extracellular cysteine is essential for
      functional recognition of P-selectin.

PMID- 9660880
TI  - Hemidesmosome formation is initiated by the beta4 integrin subunit, requires
      complex formation of beta4 and HD1/plectin, and involves a direct interaction
      between beta4 and the bullous pemphigoid antigen 180.
AB  - Hemidesmosomes (HDs) are stable anchoring structures that mediate the link
      between the intermediate filament cytoskeleton and the cell substratum. We
      investigated the contribution of various segments of the beta4 integrin
      cytoplasmic domain in the formation of HDs in transient transfection studies
      using immortalized keratinocytes derived from an epidermolysis bullosa patient
      deficient in beta4 expression. We found that the expression of wild-type beta4
      restored the ability of the beta4-deficient cells to form HDs and that distinct
      domains in the NH2- and COOH-terminal regions of the beta4 cytoplasmic domain are
      required for the localization of HD1/plectin and the bullous pemphigoid antigens
      180 (BP180) and 230 (BP230) in these HDs. The tyrosine activation motif located
      in the connecting segment (CS) of the beta4 cytoplasmic domain was dispensable
      for HD formation, although it may be involved in the efficient localization of
      BP180. Using the yeast two-hybrid system, we could demonstrate a direct
      interaction between beta4 and BP180 which involves sequences within the COOH
      terminal part of the CS and the third fibronectin type III (FNIII) repeat.
      Immunoprecipitation studies using COS-7 cells transfected with cDNAs for alpha6
      and beta4 and a mutant BP180 which lacks the collagenous extracellular domain
      confirmed the interaction of beta4 with BP180. Nevertheless, beta4 mutants which
      contained the BP180-binding region, but lacked sequences required for the
      localization of HD1/plectin, failed to localize BP180 in HDs. Additional yeast
      two- hybrid assays indicated that the 85 COOH-terminal residues of beta4 can
      interact with the first NH2-terminal pair of FNIII repeats and the CS, suggesting
      that the cytoplasmic domain of beta4 is folded back upon itself. Unfolding of the
      cytoplasmic domain may be part of a mechanism by which the interaction of beta4
      with other hemidesmosomal components, e.g., BP180, is regulated.

PMID- 9660881
TI  - Cartilage fibrils of mammals are biochemically heterogeneous: differential
      distribution of decorin and collagen IX.
AB  - Cartilage fibrils contain collagen II as the major constituent, but the presence
      of additional components, minor collagens, and noncollagenous glycoproteins is
      thought to be crucial for modulating several fibril properties. We have examined
      the distribution of two fibril constituents-decorin and collagen IX-in samples of
      fibril fragments obtained after bovine cartilage homogenization. Decorin was
      preferentially associated with a population of thicker fibril fragments from
      adult articular cartilage, but was not present on the thinnest fibrils. The
      binding was specific for the gap regions of the fibrils, and depended on the
      decorin core protein. Collagen IX, by contrast, predominated in the population
      with the thinnest fibrils, and was scarce on wider fibrils. Double-labeling
      experiments demonstrated the coexistence of decorin and collagen IX in some
      fibrils of intermediate diameter, although most fibril fragments from adult
      cartilage were strongly positive for one component and lacked the other. Fibril
      fragments from fetal epiphyseal cartilage showed a different pattern, with
      decorin and collagen IX frequently colocalized on fragments of intermediate and
      large diameters. Hence, the presence of collagen IX was not exclusive for fibrils
      of small diameter. These results establish that articular cartilage fibrils are
      biochemically heterogeneous. Different populations of fibrils share collagen II,
      but have distinct compositions with respect to macromolecules defining their
      surface properties.

PMID- 9660882
TI  - Differential roles for bone morphogenetic protein (BMP) receptor type IB and IA
      in differentiation and specification of mesenchymal precursor cells to osteoblast
      and adipocyte lineages.
AB  - Cumulative evidence indicates that osteoblasts and adipocytes share a common
      mesenchymal precursor and that bone morphogenetic proteins (BMPs) can induce both
      osteoblast and adipocyte differentiation of this precursor. In the present study,
      we investigated the roles of BMP receptors in differentiation along these
      separate lineages using a well-characterized clonal cell line, 2T3, derived from
      the mouse calvariae. BMP-2 induced 2T3 cells to differentiate into mature
      osteoblasts or adipocytes depending upon culture conditions. To test the specific
      roles of the type IA and IB BMP receptor components, truncated and constitutively
      active type IA and IB BMP receptor cDNAs were stably expressed in these cells.
      Overexpression of truncated type IB BMP receptor (trBMPR-IB) in 2T3 cells
      completely blocked BMP-2-induced osteoblast differentiation and mineralized bone
      matrix formation. Expression of trBMPR-IB also blocked mRNA expression of the
      osteoblast specific transcription factor, Osf2/ Cbfa1, and the osteoblast
      differentiation-related genes, alkaline phosphatase (ALP) and osteocalcin (OC).
      BMP-2-induced ALP activity could be rescued by transfection of wild-type (wt)
      BMPR-IB into 2T3 clones containing trBMPR-IB. Expression of a constitutively
      active BMPR-IB (caBMPR-IB) induced formation of mineralized bone matrix by 2T3
      cells without addition of BMP-2. In contrast, overexpression of trBMPR-IA blocked
      adipocyte differentiation and expression of caBMPR-IA induced adipocyte formation
      in 2T3 cells. Expression of the adipocyte differentiation-related genes, adipsin
      and PPARgamma, correlated with the distinct phenotypic changes found after
      overexpression of the appropriate mutant receptors. These results demonstrate
      that type IB and IA BMP receptors transmit different signals to bone-derived
      mesenchymal progenitors and play critical roles in both the specification and
      differentiation of osteoblasts and adipocytes.

PMID- 9660883
TI  - Regulation of Ca2+-dependent Cl- conductance in a human colonic epithelial cell
      line (T84): cross-talk between Ins(3,4,5,6)P4 and protein phosphatases.
AB  - 1. We have studied the regulation of whole-cell chloride current in T84 colonic
      epithelial cells by inositol 3,4,5,6-tetrakisphosphate (Ins(3,4,5,6)P4). New
      information was obtained using (a) microcystin and okadaic acid to inhibit
      serine/threonine protein phosphatases, and (b) a novel functional
      tetrakisphosphate analogue, 1, 2-bisdeoxy-1,2-bisfluoro-Ins(3,4,5,6)P4 (i.e. F2
      Ins(3,4,5,6)P4). 2. Calmodulin-dependent protein kinase II (CaMKII) increased
      chloride current 20-fold. This current (ICl,CaMK) continued for 7 +/- 1.2 min
      before its deactivation, or running down, by approximately 60 %. This run-down
      was prevented by okadaic acid, whereupon ICl,CaMK remained near its maximum value
      for >= 14.3 +/- 0.6 min. 3. F2-Ins(3, 4,5,6)P4 inhibited ICl,CaMK (IC50 = 100
      microM) stereo-specifically, since its enantiomer, F2-Ins(1,4,5,6)P4 had no
      effect at >= 500 microM. Dose-response data (Hill coefficient = 1.3) showed that
      F2-Ins(3,4,5,6)P4 imitated only the non-co-operative phase of inhibition by
      Ins(3,4,5,6)P4, and not the co-operative phase. 4. Ins(3,4,5,6)P4 was prevented
      from blocking ICl,CaMK by okadaic acid (IC50 = 1.5 nM) and microcystin (IC50 =
      0.15 nM); these data lead to the novel conclusion that, in situ, protein
      phosphatase activity is essential for Ins(3,4,5,6)P4 to function. The IC50 values
      indicate that more than one species of phosphatase was required. One of these may
      be PP1, since F2-Ins(3,4,5,6)P4-dependent current blocking was inhibited by
      okadaic acid and microcystin with IC50 values of 70 nM and 0.15 nM, respectively.

PMID- 9660884
TI  - Neutralization of aspartate residues in the murine inwardly rectifying K+ channel
      IRK1 affects the substate behaviour in Mg2+ block.
AB  - 1. To investigate the molecular basis of the sublevels induced in the outward
      current during block by intracellular Mg2+, single-channel currents through
      inwardly rectifying K+ (IRK1) channels were studied. 2. cDNA encoding a
      functional murine IRK1 channel was transfected into COS-1 cells (a Green Monkey
      kidney cell line) using the liposome method, and voltage clamp experiments were
      done after 48-72 h. 3. Intracellular Mg2+ at micromolar concentrations induced
      sublevels in the outward current at one-third and two-thirds of the unitary
      amplitude seen in wild-type channels. Replacing Asp 172 with Asn (D172N) and Gln
      (D172Q) abolished these sublevels, i.e. the channel showed only the fully open
      and fully blocked states. 4. Both mutations reduced the Mg2+ sensitivity of the
      channel at 2 microM Mg2+. However, the Mg2+ sensitivity did not differ
      significantly at higher concentrations (10 microM) and voltages (+70 mV). 5.
      Channels expressed from D172E showed the sublevels, indicating that a negative
      charge is indispensable to the substate behaviour. 6. Channels from tandem
      tetramers of IRK1 with one and two D172N mutant subunits mainly showed sublevels
      with two-thirds amplitude, while those from tetramers with three D172N mutant
      subunits showed no sublevels. 7. These findings suggest that differences in Mg2+
      binding patterns lead to different conductive states in a single-barrelled
      channel.

PMID- 9660885
TI  - Human sodium channel gating defects caused by missense mutations in S6 segments
      associated with myotonia: S804F and V1293I.
AB  - 1. Missense mutations in the alpha-subunit of the human skeletal muscle sodium
      channel (hSkM1) have been detected in some heritable forms of myotonia. By
      recording Na+ currents from cells transfected with cDNA encoding either wild-type
      or mutant hSkM1, we characterized the functional consequences of two myotonia
      associated mutations that lie at the cytoplasmic end of the sixth transmembrane
      segment in domain II (S804F) or domain III (V1293I). 2. Both mutations caused
      modest, but unequivocal, alterations in the voltage-dependent gating behaviour of
      hSkM1. For S804F, the abnormalities were limited to fast inactivation: the
      persistent Na+ current at the end of a 50 ms depolarization was increased 3-fold,
      the rate of inactivation from the open state was slowed 2-fold, and the voltage
      dependence of fast inactivation (h) was shifted by +3 mV. V1293I also disrupted
      fast inactivation, as evidenced by a 3-fold faster rate of recovery at
      hyperpolarized potentials (-70 mV). Activation was altered as well for V1293I:
      the voltage dependence was shifted by -6 mV (hyperpolarized). 3. Slow
      inactivation was not altered by S804F or V1293I. 4. We conclude that S804F and
      V1293I are not benign polymorphisms. Either mutation causes detectable
      alterations in channel gating and, in model simulations, the magnitude of the
      defects is sufficient to produce runs of myotonic discharges.

PMID- 9660886
TI  - Hyperpolarization-activated cationic currents (Ih) in neurones of the trigeminal
      mesencephalic nucleus of the rat.
AB  - 1. We studied the voltage-dependent current activated by membrane
      hyperpolarization in sensory proprioceptive trigeminal mesencephalic nucleus
      (MNV) neurones. 2. Membrane hyperpolarization (from -62 to -132 mV in 10 mV
      steps) activated slowly activating and non-inactivating inward currents. The
      hyperpolarization-activated currents could be described by activation curves with
      a half-maximal activation potential (V ) of -93 mV, slope (k) of 8.4 mV, and
      maximally activated currents (Imax) of around 1 nA. The reversal potential of the
      hyperpolarization-activated currents was -57 mV. 3. Extracellular Cs+ blocked
      hyperpolarization-activated currents rapidly and reversibly in a concentration
      dependent manner with an IC50 of 100 microM and Hill slope of 0.8. ZD7288 (1
      microM; 4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyridinium
      chloride), the compound developed as an inhibitor of the cardiac
      hyperpolarization-activated current (If), also blocked the hyperpolarization
      activated currents in MNV neurones. Extracellular Ba2+ (1 mM) did not affect
      hyperpolarization-activated currents. We tested whether the hyperpolarization
      activated currents contribute to the somatic membrane properties of MNV neurones
      by performing some experiments using current-clamp recording. In such experiments
      application of Cs+ (1 mM) produced no effect on neuronal resting membrane
      potentials. 4. During the course of our experiments we noticed that activating
      ATP-gated non-selective cation channels (P2X receptors) caused an inhibition of
      Ih associated with a V shift of 10 mV in the hyperpolarizing direction. This P2X
      receptor-mediated inhibition of Ih was blocked in recordings made with the rapid
      calcium chelator BAPTA (11 mM) in the pipette solution. 5. We conclude that the
      current activated by membrane hyperpolarization in MNV neurones is Ih on the
      basis of its similarity to Ih observed in other neuronal preparations. Activation
      of Ih can account for the anomalous time-dependent inward rectification that has
      previously been described in MNV neurones.

PMID- 9660887
TI  - Ca2+ images and K+ current during depolarization in smooth muscle cells of the
      guinea-pig vas deferens and urinary bladder.
AB  - 1. Electrical events and intracellular calcium concentration ([Ca2+]) imaged
      using fluo-3 and laser scanning confocal microscopy were simultaneously monitored
      in single smooth muscle cells freshly isolated from guinea-pig vas deferens or
      urinary bladder. 2. Images obtained every 8 ms, during stepping from -60 to 0 or
      +10 mV for 50 ms under voltage clamp, showed that a rise in [Ca2+] could be
      detected within 20 ms of depolarization in five to twenty small (< 2 micrometer
      diameter) 'hot spots', over 95 % of which were located within 1.5 micrometer of
      the cell membrane. Depolarization at 30 s intervals activated hot spots at the
      same places. 3. Cd2+ or verapamil abolished both hot spots and Ca2+-activated K+
      current (IK,Ca). Caffeine almost abolished hot spots and markedly reduced IK,Ca.
      Cyclopiazonic acid, which raised basal global [Ca2+], decreased the rise in hot
      spot [Ca2+] and IK,Ca amplitude during depolarization. These results suggest that
      Ca2+ entry caused Ca2+-induced Ca2+ release (CICR). 4. Under voltage clamp, hot
      spot [Ca2+] closely paralleled the rise in IK,Ca and reached a peak within 20 ms
      of the start of depolarization, but the rise in global [Ca2+] over the whole cell
      area was much slower. Step depolarization to potentials positive to -20 mV caused
      hot spots to grow in size and coalesce, leading to a rise in global [Ca2+] and
      contraction. Ca2+ hot spots also occurred during the up-stroke of an evoked
      action potential under current clamp. 5. It is concluded that the entry of Ca2+
      in the early stages of an action potential evokes CICR from discrete
      subplasmalemma Ca2+ storage sites and generates hot spots that spread to initiate
      a contraction. The activation of Ca2+-dependent K+ channels in the plasmalemma
      over hot spots initiates IK,Ca and action potential repolarization.

PMID- 9660889
TI  - Inhibition of oxidative metabolism increases persistent sodium current in rat CA1
      hippocampal neurons.
AB  - 1. Whole-cell patch-clamp recordings from freshly dissociated rat CA1 neurons
      revealed a large transient Na+ current (INa,T) and a smaller, inactivation
      resistant persistent Na+ current (INa,P). Both currents could be blocked with
      TTX. 2. The average current densities of INa,T and INa,P in thirty cells were
      111.0 +/- 9.62 and 0.87 +/- 0.13 pA pF-1, respectively. 3. Inhibiting oxidative
      phosphorylation by adding 5 mM sodium cyanide to the pipette solution
      significantly increased the amplitude of INa,P but had no significant effect on
      the amplitude of INa,T. 4. Exposing CA1 neurons to hypoxia for more than 7 min
      caused an increase in the amplitude of INa,P. There was also a delayed decrease
      in the amplitude of INa,T. 5. INa,P was more sensitive to the Na+ channel
      blockers TTX and lidocaine than INa,T. The IC50 for the effect of TTX on INa,P
      was 9.1 +/- 1.2 nM whereas the IC50 for INa,T was 37.1 +/- 1.2 nM, approximately
      4-fold higher. Lidocaine (lignocaine; 1 microM) reduced INa,P to 0.24 +/- 0.15 of
      control (n = 4) whereas INa,T was essentially unaffected (0.99 +/- 0. 11, n = 4).
      6. These results show that INa,P is increased when oxidative metabolism is
      blocked in CA1 neurons. The persistent influx of Na+ through non-inactivating Na+
      channels can be blocked by concentrations of Na+ channel blockers that do not
      affect INa,T.

PMID- 9660888
TI  - Kainate induces an intracellular Na+-activated current in cultured embryonic rat
      hippocampal neurones.
AB  - 1. In embryonic rat hippocampal neurones cultured for < 3 days, kainate induced
      an inward current at negative potentials that recovered to baseline levels
      immediately upon termination of agonist application. However, in neurones
      cultured for longer, the kainate-induced current was often followed by a long
      lasting inward current that slowly recovered to baseline levels. The amplitude of
      the delayed current (Idelay) triggered by kainate was positively related both to
      the duration of application at constant agonist concentration and to
      concentration at constant application duration. 2. Idelay could last for several
      minutes and was accompanied by a conductance increase, which closely paralleled
      current amplitude. Depression of the kainate-induced current response at receptor
      level with CNQX or at ionic level with Na+-free solution eliminated Idelay.
      However, when applied during Idelay neither CNQX nor Na+-free solution had any
      effect on Idelay. Li+ effected the same response as Na+ in mediating kainate
      induced Idelay. 3. GABA-activated Cl- current, which was associated with the same
      amount of inwardly directed charge flow at the same potential as that induced by
      kainate, did not trigger a long-lasting delayed current. 4. Idelay depended on
      the existence of extracellular K+ and its amplitude increased with the increase
      in K+ concentration. Neither applying Cl-- or Ca2+-free solutions nor increasing
      intracellular Ca2+ buffering speed and capacity altered Idelay. Exposure to the
      specific KCa channel blockers apamin and charybdotoxin also failed to alter
      Idelay. However, Idelay could be blocked by Cs+, Ba2+ and high concentrations of
      4-aminopyridine (4-AP) and TEA. 5. Inside-out excised patch-clamp recordings
      revealed that low density or highly clustered Na+-activated K+ channels were
      expressed in the cell bodies of cultured embryonic rat hippocampal neurones.
      These could be the elementary channels underlying Idelay.

PMID- 9660890
TI  - Na+-activated K+ channels in small dorsal root ganglion neurones of rat.
AB  - 1. Whole-cell Na+-activated K+ (KNa) channel currents and single KNa channels
      were studied with the patch-clamp method in small (20-25 micrometer) dorsal root
      ganglion (DRG) neurones in slices of rat dorsal root ganglia. 2. The whole-cell
      KNa channel current was identified as an additional K+-selective leakage current
      which appeared after cell perfusion with internal solutions containing different
      [Na+]. The concentration for half-maximal activation of KNa channel current was
      39 mM and the Hill coefficient was 3.5. At [Na+]i above 12 mM, KNa channel
      current dominated the unspecific leakage current. The ratio of maximum KNa
      channel current to unspecific leakage current was 45. 3. KNa channel current was
      not activated by internal Li+. It was suppressed by external 20 mM Cs+ but not by
      10 mM tetraethylammonium. 4. Single KNa channels with a conductance of 142 pS in
      155 mM external K+ (K+o)-85 mM internal K+ (K+i) solutions were observed at a
      high density of about 2 channels micrometer-2. 5. In two-electrode experiments, a
      direct correlation was seen between development of whole- cell KNa channel
      current and activation of single KNa channels during perfusion of the neurone
      with Na+-containing internal solution. 6. Under current-clamp conditions, KNa
      channels did not contribute to the action potential. However, internal perfusion
      of the neurone with Na+ shifted the resting potential towards the equilibrium
      potential for K+ (EK). Varying external [K+] indicated that in neurones perfused
      with Na+-containing internal solution the resting potential followed the EK
      values predicted by the Nernst equation over a broader voltage range than in
      neurones perfused with Na+-free solution. 7. It is concluded that the function of
      KNa channels has no links to firing behaviour but that the channels could be
      involved in setting or stabilizing the resting potential in small DRG neurones.

PMID- 9660891
TI  - A repolarization-induced transient increase in the outward current of the inward
      rectifier K+ channel in guinea-pig cardiac myocytes.
AB  - 1. Outward currents of the inwardly rectifying K+ current (IKir) in guinea-pig
      ventricular myocytes were studied in the presence of 1 mM intracellular free Mg2+
      using the whole-cell patch-clamp technique. 2. During repolarizing voltage steps
      following a large depolarizing pulse (> 0 mV), outward IKir increased transiently
      at voltages positive to the K+ equilibrium potential (EK, -84 mV for 5.4 mM
      extracellular [K+]). The rising phase was almost instantaneous, while the decay
      was exponential. The decay rate was faster at voltages closer to EK (time
      constants, 33.9 +/- 9.8 and 4.8 +/- 1.4 ms at -30 and -50 mV, respectively). 3.
      The transient outward IKir was absent when the preceding depolarization was
      applied from -40 mV. Larger transient currents developed as the voltage before
      the depolarization was shifted to more hyperpolarized levels. 4. Shift of the
      depolarizing voltage from > 0 mV to more negative ranges diminished the
      amplitudes of transient outward IKir and instantaneous inward IKir during the
      subsequent repolarizing steps positive and negative to EK, respectively. Since
      blockage of IKir by internal Mg2+ occurs upon large depolarization, and the block
      is instantaneously relieved at voltages negative to EK, the rising phase of the
      transient outward IKir was attributed to the relief of Mg2+ block at voltages
      positive to EK. Transient outward IKir was absent when intracellular [Mg2+] was
      reduced to 10 microM or lower. 5. Prolongation of the repolarizing voltage step
      increased the amplitude of time-dependent inward IKir during the subsequent
      hyperpolarization, indicating the progress of a gating process (presumably the
      channel block by intracellular polyamine) during the decaying phase of outward
      IKir. 6. Progressive prolongation of the depolarizing pulse (> 0 mV) from 100 to
      460 ms decreased the transient outward IKir amplitude during the subsequent
      repolarizing step due to slow progress of the gating (polyamine block) at > 0 mV.
      7. Current-voltage relations measured using repolarizing ramp pulses (-3.4 mV ms
      1) showed an outward hump at around -50 mV, the magnitude of which increased as
      the voltage before the conditioning depolarization (10 mV) was shifted to more
      negative levels. With slower ramp speeds (-1.5 and -0.6 mV ms-1), the hump was
      depressed at voltages near EK. 8. Our study suggests that the relief of Mg2+
      block may increase outward IKir during repolarization of cardiac action
      potentials, and that the resting potential, the level/duration of action
      potential plateau and the speed of repolarization influence the outward IKir
      amplitude. 9. A kinetic model incorporating a competition between polyamine block
      and Mg2+ block was able to account for the time dependence of outward IKir.

PMID- 9660892
TI  - Angiotensin AT1 receptor-mediated excitation of rat carotid body chemoreceptor
      afferent activity.
AB  - 1. A high density of angiotensin II receptors was observed in the rat carotid
      body by in vitro autoradiography employing 125I-[Sar1, Ile8]-angiotensin II as
      radioligand. Displacement studies demonstrated that the receptors were of the AT1
      subtype. 2. The binding pattern indicated that the AT1 receptors occurred over
      clumps of glomus cells, the principal chemoreceptor cell of the carotid body.
      Selective lesions of the sympathetic or afferent innervation of the carotid body
      had little effect on the density of receptor binding, demonstrating that the
      majority of AT1 receptors were intrinsic to the glomus cells. 3. To determine the
      direct effect of angiotensin II on chemoreceptor function, without the
      confounding effects of the vasoconstrictor action of angiotensin II, carotid
      sinus nerve activity was recorded from the isolated carotid body in vitro. The
      carotid body was superfused with Tyrode solution saturated with carbogen (95 %
      O2, 5 % CO2), maintained at 36 C, and multi-unit nerve activity recorded with a
      suction electrode. 4. Angiotensin II elicited a dose-dependent excitation of
      carotid sinus nerve activity (maximum increase of 36 +/- 11 % with 10 nM
      angiotensin II) with a threshold concentration of 1 nM. The response was blocked
      by the addition of an AT1 receptor antagonist, losartan (1 microM), but not by
      the addition of an AT2 receptor antagonist, PD123319 (1 microM). 5. In
      approximately 50 % of experiments the excitation was preceded by an inhibition of
      activity (maximum decrease of 24 +/- 8 % with 10 nM angiotensin II). This
      inhibitory response was markedly attenuated by losartan but not affected by
      PD123319. 6. These observations demonstrate that angiotensin II, acting through
      AT1 receptors located on glomus cells in the carotid body, can directly alter
      carotid chemoreceptor afferent activity. This provides a means whereby humoral
      information about fluid and electrolyte homeostasis might influence control of
      cardiorespiratory function.

PMID- 9660893
TI  - Mutual occlusion of P2X ATP receptors and nicotinic receptors on sympathetic
      neurons of the guinea-pig.
AB  - 1. The interaction of ion channels activated by nicotinic receptor agonists with
      ion channels gated by extracellular ATP (i.e. P2X receptors) was studied on
      sympathetic neurons acutely dissociated from coeliac ganglia of the guinea-pig.
      Patch clamp methods were used to measure the inward current generated through
      these non-selective cationic channels under voltage clamp. 2. At the whole cell
      level, the specific nicotinic receptor agonists nicotine (5-100 microM) or
      cytisine (50-75 microM) and the P2X receptor agonists ATP (0.1-7 microM) or
      alpha,beta-methylene ATP (6 microM) were examined separately and in the presence
      of the other receptor activator. When a nicotinic and P2X receptor agonist were
      applied together, mutually occlusive effects were generally observed. This
      occurred even with concentrations of agonists that in themselves generated little
      to no inward current. 3. The occlusive effects of nicotinic agonists on ATP-gated
      currents were blocked by the nicotinic receptor/ion channel blocker hexamethonium
      (150 microM). The occlusive effects of ATP analogues on inward currents generated
      by nicotinic agonists were blocked by the P2X receptor antagonist suramin (100
      microM). 4. Mutual occlusion of the effects of nicotinic agonists and ATP
      analogues were also observed when currents through single channels were studied
      in excised (outside-out) patches. 5. The results suggest that nicotinic receptors
      and P2X ATP receptors do not act independently in these sympathetic neurons.

PMID- 9660894
TI  - NMDA and GABAA receptors in the rat Kolliker-Fuse area control cardiorespiratory
      responses evoked by trigeminal ethmoidal nerve stimulation.
AB  - 1. Electrical stimulation (10 s) of the ethmoidal nerve (EN5) evokes the
      nasotrigeminal reflex responses, including apnoea, bradycardia and rise in
      arterial blood pressure. In the present study, we examined the involvement of N
      methyl-D-aspartate (NMDA), AMPA/kainate, (gamma-aminobutyric acidA (GABAA) and
      glycine receptors in the Kolliker-Fuse (KF) nucleus in the mediation of the
      nasotrigeminal reflex responses. 2. Unilateral injections (n = 6) of 50-100 nl of
      the NMDA receptor antagonist AP5 into the KF area led to a significant blockade
      of the EN5-evoked respiratory depression and bradycardia. Injections placed into
      the midlevel of the KF area were most effective (80-90 % blockade). The rise in
      arterial blood pressure remained unaffected. 3. Unilateral injections (n = 6) of
      the AMPA/kainate receptor antagonist CNQX into the KF area failed to block EN5
      evoked autonomic responses significantly. 4. Unilateral injections (n = 5) of the
      GABAA receptor antagonist bicuculline enhanced the EN5-evoked respiratory
      depression and bradycardia. The effect persisted for up to 30 s after
      stimulation. Bicuculline injections into the midlevel of the KF area were most
      effective. The increase in arterial blood pressure remained unaffected. 5.
      Unilateral injections (n = 5) of the glycine receptor antagonist strychnine into
      the KF area did not produce any significant effects on EN5-evoked autonomic
      responses. 6. Our results suggest that the KF area represents a mandatory relay
      for the nasotrigeminally induced apnoea and bradycardia which are predominantly
      mediated by NMDA receptors in the KF. Furthermore, it appears that KF neurons are
      under a potent GABAergic inhibitory control. The EN5-evoked rise in arterial
      blood pressure was not altered by any of the drugs and, therefore, appears not to
      be mediated via the KF.

PMID- 9660895
TI  - Expression of functional GABAA receptors in cholecystokinin-secreting gut
      neuroendocrine murine STC-1 cells.
AB  - 1. Gastrointestinal neuroendocrine (NE) cells synthesize, store and secrete gamma
      aminobutyric acid (GABA). Recently, an autocrine-paracrine function of GABA has
      been proposed for secretion from NE cells. 2. To search for functional GABAA
      receptors in NE gut cells, we performed whole-cell and perforated-patch-clamp
      studies in the intestinal cholecystokinin (CCK)-secreting NE cell line STC-1. 3.
      Application of GABA evoked currents in STC-1 cells. These effects were mimicked
      by muscimol, an agonist of GABAA receptors, and blocked by picrotoxin or
      bicuculline, antagonists of GABAA receptors. The GABA- or muscimol-activated
      currents reversed near 0 mV, which under the recording conditions used was
      consistent with the activation of the GABAA receptor-Cl- channel complex. 4. In
      contrast to the effect on most neurons, GABA as well as muscimol led to a
      (reversible) depolarization of the membrane potential of STC-1 cells. Membrane
      depolarization in turn activated voltage-gated Ca2+ channels and increased
      intracellular Ca2+ concentrations in STC-1 cells. 5. In accordance with the
      observed membrane depolarization and activation of voltage-gated Ca2+ channels,
      both GABA and muscimol stimulated Ca2+-dependent CCK release. In contrast,
      bicuculline inhibited the GABA-induced secretion of CCK. 6. Using the reverse
      transcription-polymerase chain reaction (RT-PCR), mRNA of the GABAA receptor
      subunits alpha2, alpha3, alpha5, beta1, beta3 and delta could be detected in STC
      1 cells. 7. In summary, we have shown that the CCK-secreting gut NE cell line STC
      1 expresses functional GABAA receptors and that GABA stimulates CCK release.
      Thus, GABA is involved in the fine tuning of CCK secretion from the gut NE cell
      line STC-1.

PMID- 9660896
TI  - Metabotropic and ionotropic glutamate receptors regulate calcium channel currents
      in salamander retinal ganglion cells.
AB  - 1. Glutamate suppressed high-voltage-activated barium currents (IBa, HVA) in
      tiger salamander retinal ganglion cells. Both ionotropic (iGluR) and metabotropic
      (mGluR) receptors contributed to this calcium channel inhibition. 2. Trans-ACPD
      (1-aminocyclopentane-trans-1S,3R-dicarboxylic acid), a broad-spectrum
      metabotropic glutamate receptor agonist, suppressed a dihydropyridine-sensitive
      barium current. Kainate, an ionotropic glutamate receptor agonist, reduced an
      omega-conotoxin GVIA-sensitive current. 3. The relative effectiveness of
      selective agonists indicated that the predominant metabotropic receptor was the L
      2-amino-4-phosphonobutyrate (L-AP4)-sensitive, group III receptor. This receptor
      reversed the action of forskolin, but this was not responsible for calcium
      channel suppression. l-AP4 raised internal calcium concentration. Antagonists of
      phospholipase C, inositol trisphosphate (IP3) receptors and ryanodine receptors
      inhibited the action of metabotropic agonists, indicating that group III receptor
      transduction was linked to this pathway. 4. The action of kainate was partially
      suppressed by BAPTA, by calmodulin antagonists and by blockers of calmodulin
      dependent phosphatase. Suppression by kainate of the calcium channel current was
      more rapid when calcium was the charge carrier, instead of barium. The results
      indicate that calcium influx through kainate-sensitive glutamate receptors can
      activate calmodulin, which stimulates phosphatases that may directly suppress
      voltage-sensitive calcium channels. 5. Thus, ionotropic and metabotropic
      glutamate receptors inhibit distinct calcium channels. They could act
      synergistically, since both increase internal calcium. These pathways provide
      negative feedback that can reduce calcium influx when ganglion cells are
      depolarized.

PMID- 9660897
TI  - Characterization of sensory and corticothalamic excitatory inputs to rat
      thalamocortical neurones in vitro.
AB  - 1. Using an in vitro slice preparation of the rat dorsal lateral geniculate
      nucleus (dLGN), the properties of retinogeniculate and corticothalamic inputs to
      thalamocortical (TC) neurones were examined in the absence of GABAergic
      inhibition. 2. The retinogeniculate EPSP evoked at low frequency (>= 0.1 Hz)
      consisted of one or two fast-rising (0.8 +/- 0.1 ms), large-amplitude (10.3 +/-
      1.6 mV) unitary events, while the corticothalamic EPSP had a graded relationship
      with stimulus intensity, owing to its slower-rising (2.9 +/- 0.4 ms), smaller
      amplitude (1.3 +/- 0.3 mV) estimated unitary components. 3. The retinogeniculate
      EPSP exhibited a paired-pulse depression of 60.3 +/- 5.6 % at 10 Hz, while the
      corticothalamic EPSP exhibited a paired-pulse facilitation of > 150 %. This
      frequency-dependent depression of the retinogeniculate EPSP was maximal after the
      second stimulus, while the frequency-dependent facilitation of the
      corticothalamic EPSP was maximal after the fourth or fifth stimulus, at
      interstimulus frequencies of 1-10 Hz. 4. There was a short-term enhancement of
      the >= 0.1 Hz corticothalamic EPSP (64.6 +/- 9.2 %), but not the retinogeniculate
      EPSP, following trains of stimuli at 50 Hz. 5. The >= 0.1 Hz corticothalamic EPSP
      was markedly depressed by the non-NMDA antagonist 1-(4-amino-phenyl)-4-methyl-7,8
      methylene-dioxy-5H-2, 3-benzodiazepine (GYKI 52466), but only modestly by the
      NMDA antagonist 3-((RS)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid ((RS)
      CPP), and completely blocked by the co-application of GYKI 52466, 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX), (RS)-CPP and (5R, 10S)-(+)-5-methyl-10,11
      dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine (MK-801). Likewise, the
      corticothalamic responses to trains of stimuli (1-500 Hz) were greatly reduced by
      this combination of ionotropic glutamate receptor antagonists. 6. In the presence
      of GYKI 52466, CNQX, (RS)-CPP and MK-801, residual corticothalamic responses and
      slow EPSPs, with a time to peak of 2-10 s, could be generated following trains of
      five to fifty stimuli. Neither of these responses were occluded by 1S,3R-1
      aminocyclopentane-1, 3-dicarboxylic acid (1S,3R-ACPD), suggesting they are not
      mediated via group I and II metabotropic glutamate receptors.

PMID- 9660898
TI  - Submillisecond kinetics and low efficacy of parallel fibre-Golgi cell synaptic
      currents in the rat cerebellum.
AB  - 1. The whole-cell configuration of the patch clamp technique was used to record
      from Golgi cells in thin slices of the rat cerebellum (P12-P25). Their active
      membrane properties and the input that they receive from the parallel fibres were
      characterized. 2. Most cells were filled with biocytin and morphologically
      identified by the presence of a large axonal arbor restricted to the granular
      layer. The morphological parameters of eighteen of the best-preserved cells were
      quantified. 3. A slow capacitive current transient, characteristic of the Golgi
      cell axon, was used to identify Golgi cells whenever their morphology could not
      be preserved. 4. Golgi cells fire action potentials spontaneously at 3 +/- 1.7 Hz
      (n = 17). Their firing frequency increases linearly with the amplitude of
      depolarizing current pulses and displays marked adaptation. 5. When
      hyperpolarized Golgi cells display an anomalous rectification which is blocked by
      2 mM CsCl, indicating the presence of an Ih-like current. 6. Golgi cells receive
      a spontaneous excitatory input from parallel fibres. This input is composed of
      small amplitude, mostly monoquantal, EPSCs. Chemical stimulation of granule cells
      by locally applied kainate evokes tetrodotoxin (TTX)-dependent events with
      similar properties. 7. The parallel fibre-Golgi cell EPSCs have both AMPA and
      NMDA components. The NMDA component is blocked by 1 mM external magnesium at -60
      mV and decays with time constants of 31 +/- 9 ms and 170 +/- 15 ms (at +61 mV in
      the presence of magnesium). 8. In the presence of 10 microM internal spermine,
      the AMPA component of the spontaneous EPSCs is markedly slowed (0.96 +/- 0.25 ms
      to 1.86 +/- 0.47 ms; n = 4) and reduced in amplitude (49 +/- 7 %; n = 4) when
      depolarizing the cell from -70 mV to +61 mV. 9. The decay kinetics of individual
      AMPA EPSCs were found to be variable, in part because of dendritic filtering. A
      more detailed analysis reveals that the synaptic AMPA conductances are regulated
      during development and close faster at days P19-P25 than at days P13-P16.10.
      These data suggest that the efficacy of the parallel fibre-Golgi cell input is
      rather low. This places strong constraints on the conditions in which the
      inhibitory feedback exerted by the Golgi cell can be operational.11. The
      possibility is considered that the Golgi cell-granule cell circuit shows an
      oscillatory behaviour. This hypothesis is discussed in relation to the models of
      Albus and Marr.

PMID- 9660899
TI  - Cannabinoids decrease excitatory synaptic transmission and impair long-term
      depression in rat cerebellar Purkinje cells.
AB  - 1. CB-1 cannabinoid receptors are strongly expressed in the molecular layer of
      the cerebellar cortex. We have analysed, in patch-clamped Purkinje cells (PCs) in
      rat cerebellar slices, the effect of the selective CB-1 agonists WIN55,212-2 and
      CP55,940 and of the selective CB-1 antagonist SR141716-A on excitatory synaptic
      transmission and synaptic plasticity. 2. Bath application of both agonists
      markedly depressed parallel fibre (PF) EPSCs. This effect was reversed by
      SR141716-A. In contrast, responses of PCs to ionophoretic application of
      glutamate were not affected by WIN55, 212-2. 3. The coefficient of variation and
      the paired-pulse facilitation of these PF-mediated EPSCs increased in the
      presence of WIN55,212-2. 4. WIN55,212-2 decreased the frequency of miniature
      EPSCs and of asynchronous synaptic events evoked in the presence of strontium in
      the bath, but did not affect their amplitude. 5. WIN55, 212-2 did not change the
      excitability of PFs. 6. WIN55,212-2 impaired long-term depression induced by
      pairing protocols in PCs. This effect was antagonized by SR141716-A. The same
      impairment of LTD was produced by 2-chloroadenosine, a compound that decreases
      the probability of release of glutamate at PF-PC synapses. 7. The present study
      demonstrates that cannabinoids inhibit synaptic transmission at PF-PC synapses by
      decreasing the probability of release of glutamate, and thereby impair LTD. These
      two effects might represent a plausible cellular mechanism underlying cerebellar
      dysfunction caused by cannabinoids.

PMID- 9660900
TI  - Locus of frequency-dependent depression identified with multiple-probability
      fluctuation analysis at rat climbing fibre-Purkinje cell synapses.
AB  - 1. EPSCs were recorded under whole-cell voltage clamp at room temperature from
      Purkinje cells in slices of cerebellum from 12- to 14-day-old rats. EPSCs from
      individual climbing fibre (CF) inputs were identified on the basis of their large
      size, paired-pulse depression and all-or-none appearance in response to a graded
      stimulus. 2. Synaptic transmission was investigated over a wide range of
      experimentally imposed release probabilities by analysing fluctuations in the
      peak of the EPSC. Release probability was manipulated by altering the
      extracellular [Ca2+] and [Mg2+]. Quantal parameters were estimated from plots of
      coefficient of variation (CV) or variance against mean conductance by fitting a
      multinomial model that incorporated both spatial variation in quantal size and
      non-uniform release probability. This 'multiple-probability fluctuation' (MPF)
      analysis gave an estimate of 510 +/- 50 for the number of functional release
      sites (N) and a quantal size (q) of 0.5 +/- 0.03 nS (n = 6). 3. Control
      experiments, and simulations examining the effects of non-uniform release
      probability, indicate that MPF analysis provides a reliable estimate of quantal
      parameters. Direct measurement of quantal amplitudes in the presence of 5 mM
      Sr2+, which gave asynchronous release, yielded distributions with a mean quantal
      size of 0.55 +/- 0.01 nS and a CV of 0.37 +/- 0.01 (n = 4). Similar estimates of
      q were obtained in 2 mM Ca2+ when release probability was lowered with the
      calcium channel blocker Cd2+. The non-NMDA receptor antagonist 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX; 1 microM) reduced both the evoked current and
      the quantal size (estimated with MPF analysis) to a similar degree, but did not
      affect the estimate of N. 4. We used MPF analysis to identify those quantal
      parameters that change during frequency-dependent depression at climbing fibre
      Purkinje cell synaptic connections. At low stimulation frequencies, the mean
      release probability (pr) was unusually high (0.90 +/- 0.03 at 0.033 Hz, n = 5),
      but as the frequency of stimulation was increased, pr fell dramatically (0.02 +/-
      0.01 at 10 Hz, n = 4) with no apparent change in either q or N. This indicates
      that the observed 50-fold depression in EPSC amplitude is presynaptic in origin.
      5. Presynaptic frequency-dependent depression was investigated with double-pulse
      and multiple-pulse protocols. EPSC recovery, following simultaneous release at
      practically all sites, was slow, being well fitted by the sum of two exponential
      functions (time constants of 0.35 +/- 0.09 and 3.2 +/- 0.4 s, n = 5). EPSC
      recovery following sustained stimulation was even slower. We propose that
      presynaptic depression at CF synapses reflects a slow recovery of release
      probability following release of each quantum of transmitter. 6. The large number
      of functional release sites, relatively large quantal size, and unusual dynamics
      of transmitter release at the CF synapse appear specialized to ensure highly
      reliable olivocerebellar transmission at low frequencies but to limit
      transmission at higher frequencies.

PMID- 9660901
TI  - Mechanistic analyses of ion dependences in a high-affinity human serotonin
      transport system in transfected murine fibroblast cells.
AB  - 1. A clonal cell line, L-S1, has been identified from transfection of human
      genomic DNA into cultured mouse L-M fibroblasts. Because this transfectant cell
      line stably expresses a high-affinity serotonin (5-HT) transport mechanism with
      kinetic and pharmacological properties comparable to those of other serotonin
      uptake systems, it was used to investigate the mechanistic involvement of Na+ and
      Cl- ions in the ligand binding and kinetic uptake processes of this system. 2.
      Intact transfectant cells, when incubated at low temperature (4 C), enabled
      quantitative assessment of imipramine-displaceable 5-[3H]HT binding to the 5-HT
      transport system. This binding activity is insensitive to the presence of various
      ligands specific for 5-HT receptor subtypes. 3. Imipramine-displaceable 5-[3H]HT
      binding to intact L-S1 cells was shown to be a Cl--dependent but Na+-independent
      process. Chloride ions lack binding co-operativity in facilitating ligand
      binding. Changes in external Cl- concentration altered the Kd but not the Bmax of
      binding. 4. The overall transport activity was observed to be highly dependent on
      both external Na+ and Cl- concentrations, characterized by a 5-HT:Na+:Cl-
      coupling ratio of 1:1:1 per transport cycle. Alterations in the external
      concentrations of both Na+ and Cl- ions altered only the Km and not the Vmax of
      transport. 5. Both binding and kinetic results are consistent with kinetic
      modelling predictions of the Cl- ion in facilitating 5-HT binding to the
      transport system, and of the Na+ ion in enabling translocation of bound 5-HT
      across the plasma membrane. Thus, Na+ and Cl- ions facilitate mechanistically
      distinct and discernible functions in the transport cycle.

PMID- 9660902
TI  - Sympathetic attenuation of parasympathetic vasodilatation in oro-facial areas in
      the cat.
AB  - 1. The present study was designed to examine the interaction between sympathetic
      and parasympathetic influences on blood flow in oro-facial areas such as lower
      lip, palate and submandibular gland (SMG) and in the common carotid artery (CCA)
      in anaesthetized cats. 2. Section of the ipsilateral superior cervical
      sympathetic trunk (CST) increased the basal CCA blood flow significantly. The
      control level with the nerve intact was comparable with that seen at 0.5-1 Hz CST
      stimulation, suggesting a spontaneous discharge of around 0. 5-1 Hz in the CST
      fibres innervating the beds supplied by the CCA. The basal blood flow at all
      sites examined was reduced by CST stimulation in a frequency-dependent manner. 3.
      Electrical stimulation of the central end of the lingual nerve (LN) evoked blood
      flow increases in the lower lip and palate. These blood flow increases were
      markedly reduced by concurrent CST stimulation in a manner that was frequency
      dependent, but not simply related to the vasoconstrictor effect of CST
      stimulation. This effect of CST stimulation was not observed in tongue or SMG,
      even though CST stimulation evoked vasoconstriction in these tissues. A
      significant reduction in the level of CCA blood flow attained during LN
      stimulation was observed on repetitive CST stimulation only at 10 Hz, indicating
      that this response behaved in a fashion different from that seen in the lower
      lip, palate, tongue and SMG. 4. The present study suggests that concurrent
      repetitive CST stimulation reduces parasympathetically mediated blood flow
      increases in certain oro-facial areas (such as the lower lip and palate), but not
      in the tongue and SMG. This inhibitory action was not a simple additive effect
      (between vasoconstriction and vasodilatation) and it disappeared rapidly after
      the cessation of CST stimulation.

PMID- 9660903
TI  - Signalling of static and dynamic features of muscle spindle input by cuneate
      neurones in the cat.
AB  - 1. The capacity of cuneate neurones to signal information derived from muscle
      spindle afferent fibres about static stretch or vibration of forearm extensor
      muscles was examined electrophysiologically in anaesthetized cats. 2. Static
      stretch (>= 2 mm in amplitude) and sinusoidal vibration (at frequencies of 50-800
      Hz) were applied longitudinally to individual muscle tendons by means of a
      feedback controlled mechanical stimulator, and responses were recorded from
      individual cuneate neurones and from individual spindle afferent fibres. 3.
      Cuneate neurones sampled were located caudal to the obex and displayed a
      sensitivity to both vibration and static stretch of forearm muscles that was
      consistent with their input arising from primary spindle endings. In response to
      static muscle stretch, they displayed graded and approximately linear stimulus
      response relations, and a stability of response level at fixed lengths that was
      consistent with these neurones contributing discriminative information about
      static muscle stretch. 4. In response to sinusoidal muscle vibration the cuneate
      neurones also showed graded stimulus-response relations (in contrast to spindle
      afferents which at low vibration amplitudes attain a plateau response level
      corresponding to a discharge of 1 impulse on each vibration cycle). Lowest
      thresholds were at 100-300 Hz and bandwidths of vibration sensitivity extended up
      to approximately 800 Hz. 5. Temporal precision in cuneate responses to muscle
      vibration was assessed by constructing phase scatter and cycle histograms from
      which measures of vector strength could be calculated. Cuneate responses
      displayed somewhat poorer phase locking (and lower vector strengths) than spindle
      afferent responses to vibration (a reflection of uncertainties associated with
      synaptic transmission). Nevertheless, the remarkable feature of cuneate responses
      to muscle vibration is the preservation of tight phase locking at frequencies up
      to 400-500 Hz, which presumably enables these central neurones to contribute
      accurate temporal information for the kinaesthetic sense in a variety of
      circumstances involving dynamic perturbations to skeletal muscle.

PMID- 9660904
TI  - A cross-bridge mechanism can explain the thixotropic short-range elastic
      component of relaxed frog skeletal muscle.
AB  - 1. The passive tension and sarcomere length of relaxed frog skeletal muscle
      fibres were measured in response to imposed length stretches. The tension
      response to a constant-velocity stretch exhibited a clear discontinuity. Tension
      rose more rapidly during the initial approximately 0.4 % L0 of the stretch than
      during the latter stages (where L0 is the resting length of the fibre). This
      initial tension response is attributed to the short-range elastic component
      (SREC). 2. The use of paired triangular stretches revealed that the maximum
      tension produced during the SREC response of the second stretch was significantly
      reduced by the first stretch. This history-dependent behaviour of the SREC
      reflects thixotropic stiffness changes that have been previously described in
      relaxed muscle. 3. The biphasic nature of the SREC tension response to movement
      was most apparent during the first imposed length change after a period at a
      fixed length, irrespective of the direction of movement. 4. If a relaxed muscle
      was subjected to an imposed triangular length change so that the muscle was
      initially stretched and subsequently shortened back to its original fibre length,
      the resting tension at the end of the stretch was reduced relative to its initial
      pre-stretch value. Following the end of the stretch, tension slowly increased
      towards its initial value but the tension recovery was not accompanied by a
      contemporaneous increase in sarcomere length. This finding suggests that the
      resting tension of a relaxed muscle fibre is not entirely due to passive
      elasticity. The results are compatible with the suggestion that a portion of the
      resting tension - the filamentary resting tension (FRT) - is produced by a low
      level of active force generation. 5. If a second identical stretch was imposed on
      the muscle at a time when the resting tension was reduced by the previous
      stretch, the maximal tension produced during the second stretch was the same as
      that produced during the first, despite the second stretch commencing from a
      lower initial resting tension. 6. In experiments using paired triangular length
      changes, an inter-stretch interval of zero did not produce a substantially
      greater thixotropic reduction in the second stretch elastic limit force than an
      inter-stretch interval in the range 0.5-1 s. 7. A theoretical model was developed
      in which the SREC and FRT arise as manifestations of a small number of slowly
      cycling cross-bridges linking the actin and myosin filaments of a relaxed
      skeletal muscle. The predictions of the model are compatible with many of the
      experimental observations. If the SREC and FRT are indeed due to cross-bridge
      activity, the model suggests that the cross-bridge attachment rate must increase
      during interfilamentary movement. A mechanism (based on misregistration between
      the actin binding sites and the myosin cross-bridges) by which this might arise
      is presented.

PMID- 9660905
TI  - The effect of rapid eye movement (REM) sleep on upper airway mechanics in normal
      human subjects.
AB  - 1. It has been proposed that the upper airway is more compliant during rapid eye
      movement (REM) sleep than during non-rapid eye movement (NREM) sleep. The purpose
      of this study was to test this hypothesis in a group of subjects without sleep
      disordered breathing. 2. On the first night, the effect of sleep stage on the
      relationship of retropalatal cross-sectional area (CSA; visualized with a fibre
      optic scope) to pharyngeal pressure (PPH) measured at the soft palate during
      eupnoeic breathing was studied. Breaths during REM sleep were divided into phasic
      (associated with eye movements) and tonic (not associated with eye movements).
      There was a significant decrease in pharyngeal CSA during NREM sleep compared
      with wakefulness. There was no further decrease observed during either tonic or
      phasic REM sleep. Pharyngeal compliance, defined as the slope of the regression
      CSA versus PPH, was significantly increased during NREM sleep compared with
      wakefulness and REM sleep, with the compliance during both tonic and phasic REM
      sleep being similar to that observed in wakefulness. 3. On the second night, the
      effect of sleep stage on pressure-flow relationships of the upper airway was
      investigated. There was a trend towards the upper airway resistance being highest
      in NREM sleep compared with wakefulness and REM sleep. 4. We conclude that the
      upper airway is stiffer and less compliant during REM sleep than during NREM
      sleep. We postulate that this difference is secondary to differences in upper
      airway vascular perfusion between REM and NREM sleep.

PMID- 9660906
TI  - Changes in Achilles tendon moment arm from rest to maximum isometric
      plantarflexion: in vivo observations in man.
AB  - 1. The purpose of the present study was to examine the effect of a plantarflexor
      maximum voluntary contraction (MVC) on Achilles tendon moment arm length. 2.
      Sagittal magnetic resonance (MR) images of the right ankle were taken in six
      subjects both at rest and during a plantarflexor MVC in the supine position at a
      knee angle of 90 deg and at ankle angles of -30 deg (dorsiflexed direction), -15
      deg, 0 deg (neutral ankle position), +15 deg (plantarflexed direction), +30 deg
      and +45 deg. A system of mechanical stops, support triangles and velcro straps
      was used to secure the subject in the above positions. Location of a moving
      centre of rotation was calculated for ankle rotations from -30 to 0 deg, -15 to
      +15 deg, 0 to +30 deg and +15 to +45 deg. All instant centres of rotation were
      calculated both at rest and during MVC. Achilles tendon moment arms were measured
      at ankle angles of -15, 0, +15 and +30 deg. 3. At any given ankle angle, Achilles
      tendon moment arm length during MVC increased by 1-1.5 cm (22-27 %, P < 0.01)
      compared with rest. This was attributed to a displacement of both Achilles tendon
      by 0.6-1.1 cm (P < 0.01) and all instant centres of rotation by about 0.3 cm (P <
      0.05) away from their corresponding resting positions. 4. The findings of this
      study have important implications for estimating loads in the musculoskeletal
      system. Substantially unrealistic Achilles tendon forces and moments generated
      around the ankle joint during a plantarflexor MVC would be calculated using
      resting Achilles tendon moment arm measurements.

PMID- 9660907
TI  - Extended operation for T4 lung carcinoma.
AB  - The extended surgery for T4 lung carcinoma was reviewed. From literature in the
      last decade, the 5-year survival rate has been under 10% worldwide. However a
      more favorable prognosis will be expected nowadays because of the progress of
      perioperative intensive care and appearance of effective anticancerous agents for
      induction chemotherapy. We compared the results of surgery for T4 lung carcinoma
      from 1978 to 1989, to those from 1992 to 1997. The 3 and 5-year survivals in the
      former period were 6.8% respectively, however in the latter period the 3-year
      survival rate rose to 24.6%. In patients with T4, the prognoses are different
      according to the involved organs by lung carcinoma. Generally, combined resection
      of the trachea, carina, descending aorta and left atrium show better prognoses
      compared to that of the esophagus and liver. We consider that malignant pleural
      effusion with N2 should not be the object for panpleuropneumonectomy. In our
      series from 1992 to 1997 median survival time (MST) of T4 with N0 or N1 was 25.5
      months, on the other hand MST with N2 or N3 was 14.2 months. Histologically
      patients with squamous cell carcinoma showed a better prognosis than those with
      adenocarcinoma. From these results, in the extended operation for T4 we may
      expect more favorable prognoses in cases with involvements of the trachea,
      carina, aorta and left atrium, and with N0 or N1, histologically squamous cell
      carcinoma.

PMID- 9660908
TI  - Transmyocardial laser revascularization (TMLR): a long way to the first
      successful clinical application in the world.
AB  - Much attention has been paid to surgical intervention for those patients with
      small branches or diffuse stenotic lesions of the coronary arteries, for whom
      coronary artery bypass grafting can not be carried out at all. For resolving
      these problems, we have planned to supply arterial blood from the left
      ventricular cavity into the ischemic myocardium through laser channels created by
      laser into the myocardium. It was obviously recognized that arterial blood could
      be hemodynamically supplied from the left ventricular cavity into the ischemic
      myocardium. In trials on dogs, laser channels 0.2 mm in diameter have been shown
      microscopically to be patent even 3 years after TMLR. Thus, this procedure could
      be used as a new method of transmyocardial revascularization. Subsequently, TMLR
      was applied in a 55-year-old male patient with severe angina pectoris who had
      undergone pericardiectomy 7 years before. He is still alive 12 years after TMLR.
      This patient was the first successful clinical case treated by TMLR alone, in the
      world.

PMID- 9660909
TI  - Hypoplastic left heart syndrome: "Which is the best operative strategy?".
AB  - Therapy for the hypoplastic left heart syndrome (HLHS) is still under debate. We
      report about our experience in the treatment of this cardiac malformation using
      heart transplantation and Norwood palliation. From 1988 to 1997 a total number of
      30 infants with hypoplastic left heart underwent heart transplantation. Mean age
      at transplantation was 66 days. Mean waiting time was 53 days. Donor-recipient
      weight ratio ranged from 0.6 to 3.9. There were 6 early hospital deaths and one
      late death until now. Causes of death were rejection (3), right heart failure
      (2), infection (1) and multi system organ failure (1). Overall survival was 77%.
      Increasing experience improved results substantially. From 1988 to 1993 (n=12)
      survival rate was 58%, whereas from 1994 to 1997 (n=18) survival rate increased
      to 88%. Quality of life is excellent in the 23 surviving infants. Only one infant
      shows severe morbidity (neurological defect). The Norwood procedure has been
      performed in 18 patients since 1993. Five patients died after the first stage. Up
      until now 10 infants have undergone the second stage and one infant the third
      stage procedure. None of them have died. Survival rate is 72% for the whole
      group. Taking into account that 12 infants died on the waiting list for
      transplanatation (28%), we have comparable results in terms of the survival rate
      for transplantation and the Norwood procedure in infants with HLHS since 1994.
      However quality of life and physical development are far better in infants after
      transplantation according to our experience. Therefore we prefer, whenever
      possible heart transplantation in the treatment of hypoplastic left heart
      syndrome. Certainly not all infants with this malformation can undergo
      transplantation because of the lack of donor organs. Criteria for the decision
      regarding the operative strategy in our opinion are function of the right
      ventricle and tricuspid valve, size of the interaterial communication and
      parental request.

PMID- 9660910
TI  - Left atrial myxoma with an atrial septal defect: a case report and review of the
      literature.
AB  - We report a case of a 49 year-old Japanese woman with a left atrial myxoma
      complicated by an atrial septal defect diagnosed intraoperatively, which was
      classified as in secundum defect and was 28x110 mm in diameter. The tumor, which
      was attached by a pedicle to the posterior wall of the left atrium near the
      posterior commissure of the mitral valve, was removed together with a small
      portion of the left atrial wall. The postoperative course was uneventful. The
      pathologic findings were consistent with the diagnosis of myxoma. Since the
      defect was functionally canceled by the myxoma, the diagnosis of an atrial septal
      defect was not confirmed preoperatively even by color Doppler echocardiography
      and cardiac catheterization. Tumor embolization is one of the critical
      complications of myxoma. Fortunately, she didn't suffer from either systemic or
      pulmonary emboli. During surgery of myxoma with atrial septal defect, careful
      manipulation is needed, especially at caval cannulation so as not to damage the
      tumor directly. In the cases with atrial septal defect or patent foramen ovale,
      myxomas are generally situated on the interatrial septum. However, in this case
      the tumor was located on the posterior wall of the left atrium.

PMID- 9660911
TI  - A three year experience with the toronto stentless porcine valve.
AB  - In the three year period from March 1994, 112 Toronto Stentless Porcine Valves
      (SPV TM) were implanted in the Western Infirmary, Glasgow. There were 55 males
      and 57 females aged between 45 and 86 years (mean 70.9 +/- 7.2 yrs). The mean
      preoperative aortic gradient was 89 +/- 27 mmHg. Fifty-three patients (47%) had
      an isolated first time aortic valve replacement. Myocardial revascularisation was
      carried out in 51 patients (46%) with a mean of 1.7 +/- 0.9 coronary bypass
      grafts per patient. Six patients (5.3%) had associated mitral valve procedures
      and six patients (5.3%) had previous open heart surgery. Four patients (3.6%) had
      a minimally invasive procedure. There was one perioperative death (0.9%) which
      was not valve related. Of the 111 survivors there were three late deaths
      (cerebrovascular accident at two months and congestive cardiac failure at two
      months and four months). Two patients developed prosthetic valve endocarditis at
      three and five months respectively, one requiring a repair of a periprosthetic
      leak. To compare the effects of stented and stentless prostheses on early
      haemodynamic function and late left ventricular mass regression, a prospective
      randomized clinical trial was conducted. Following valve sizing, 20 patients were
      randomized to receive a Carpentier-Edwards SAV stented bioprosthesis (mean
      annular size-25.3 mm, mean valve size-23 mm) of which eight also had bypass
      grafts. Twenty patients were randomized to receive a Toronto SPV (mean annular
      size-25.5 mm, mean valve size-26 mm) of which nine had bypass grafts. The
      stentless valve group had a longer ischaemic time (77.9 +/- 20.9 min v 60.9 +/-
      21.9 min) and bypass time (101.7 +/- 27.1 min v 82.9 +/- 20.2 min). Using
      continuous cardiac output monitoring, no statistically significant differences
      were found in early haemodynamic indices although the stentless group required
      less inotropes and had a shorter ventilation time (16.1 +/- 4.2 hrs v 55.2 +/-
      104.9 hrs) and intensive care stay (1.1 +/- 0.2 days v 4.6 +/- 8.3 days). Mean
      and peak aortic gradients one week postoperatively were lower in the stentless
      group (5.6 +/- 3 mmHg v 8.9 +/- 2.3 mmHg and 12.5 +/- 7.8 mmHg v 24.4 +/- 8.8
      mmHg respectively). Magnetic resonance imaging at six months showed a 15%
      reduction in the end systolic muscle mass index in the stented group but a
      greater reduction of 29% in the stentless group. This study shows that despite
      requiring a more demanding technique of insertion, aortic valve replacement with
      the Toronto stentless porcine valve can produce satisfactory early clinical
      results.

PMID- 9660912
TI  - Coronary artery bypass grafting without cardiopulmonary bypass.
AB  - Coronary artery bypass surgery on a beating heart is now an accepted modality to
      treat selected patients of ischaemic heart disease. From June '92 through Sep
      '97, 162 patients underwent this procedure. There was no mortality and none of
      the patients had any respiratory or neurological morbidity, though 24% of the
      patients form a high risk group for conventional coronary bypass surgery. It is
      definitely cost effective in comparison to any other modalities for treatment of
      ischaemic heart disease. We conclude that continous use of this technique is
      justified and all cardiac surgeons should have exposure to this procedure.

PMID- 9660913
TI  - Lung volume reduction surgery for pulmonary emphysema using dynamic Xenon-133 and
      Tc-99m-MAA SPECT images.
AB  - The usefulness of Xe-133 and Tc-99m-MAA single photon emission computed
      tomography (SPECT) in identifying areas to be resected during video-assisted
      thoracoscopic lung reduction surgery for emphysema was examined. Twenty-nine
      patients with advanced emphysema were examined using Xe-133 and Tc-99m-MAA SPECT
      prior to and following surgery. For the Xe-133 dynamic SPECT, patients inhaled Xe
      133 gas for 6 minutes. Equilibrium and subsequent washout SPECT images were
      acquired every 30 seconds for 6 to 7 minutes during spontaneous breathing.
      Ventilation was quantified by Xe-133 clearance time (T1/2) in addition to visual
      assessment. The patients underwent unilateral thoracoscopic volume reduction in
      the regions with abnormal Xe-133 retention and Tc-99m-MAA defect. All patients
      demonstrated marked, heterogeneous Xe-133 retention and Tc-99m-MAA defects
      preoperatively. The worst functioning areas were identified as nonventilated and
      noflow areas, or areas with air trapping and low perfusion. These changes were
      found even in patients with diffuse and symmetrical impairments on chest CT.
      After surgery, most of these "target areas" disappeared and pulmonary function
      tests demonstrated significant improvement. T1/2 correlated closely with the
      percent predicted FEV1 (%FEV) and 6-minute walk distance before and after surgery
      (p<0.0001). Xe-133 and Tc-99m-MAA SPECT imaging was useful in identifying "target
      areas" in the emphysematous lung. Directed unilateral thoracoscopic volume
      reduction based on these SPECT images is an effective treatment for emphysema.

PMID- 9660914
TI  - Cavitating adenocarcinoma of the lung.
AB  - The characteristics and outcomes of resected adenocarcinoma with cavity formation
      were studied in 7 cases, which were 14.9% of all 47 resected adenocarcinomas in
      the past three years. Tumor size was less than 3 cm in diameter in 3 cases, 3 to
      5 cm in 2 and more than 5 cm in 2. Cavities were multiple in 4 cases and single
      in 3. Cavities were divided into 4 types pathologically. 1. Central necrosis
      type: central ischemia was suspected. This type was observed in 2 cases that died
      due to cancer. 2. Cancer cell lining type: the inner wall of the cavity was lined
      by viable cancer cells without necrosis. The cause of this type may be detachment
      of the central portion of a papillary growth tumor without necrosis. One of three
      patients died from cancer. The others are alive without recurrence. 3. Bronchial
      expansion type: the inner wall was composed of cancer cells and bronchus. This
      may be caused by ectatic change of peripheral bronchi following tumor invasion to
      more central bronchi. One of this type of case died due to myocardial infarction.
      4. Alveolar expansion type: the inner wall was composed of cancer cells and
      alveoli. Detachment of destroyed alveoli or invasion along the wall of cavities
      of a honeycomb lung was suspected as a possible cause. One of this type of case
      is alive. Cavity formation can occur in adenocarcinoma even when the tumor is
      small. However there were few inflammatory related findings in adenocarcinoma
      with cavity formation. The outcome of the central necrosis type was especially
      poor, suggesting rapid tumor growth.

PMID- 9660915
TI  - Coronary artery bypass grafting for an adult with coronary disease due to
      Kawasaki disease.
AB  - Surgical treatment for patients over the age of forty with coronary aneurysms
      associated with Kawasaki disease is rare. We report on a 47-year-old man who
      underwent coronary artery bypass grafting using the left internal thoracic
      arteries (ITA) and right gastroepiploic (GEA). The postoperative course was
      uneventful. One month later, the normal stress thallium-201 myocardial perfusion
      imaging was normal and coronary angiography showed good patency for the ITA, GEA,
      and saphenous vein grafts. He had some coronary risk factors including smoking,
      hypertension and hyperlipidemia. Histological examination of a sample shows that
      the coronary artery sequelae of Kawasaki disease have already become part of
      increasing burden of adult ischemic heart disease.

PMID- 9660916
TI  - Surgical removal of a stent entrapped in the left main coronary artery.
AB  - A stent entrapped in the coronary artery, which can not be removed by a trans
      catheter approach, is extremely rare but is the biggest problem cardiologists
      face. Surgical retrieval appears to be the only possible treatment to avoid
      sudden death due to stent thrombosis. We experienced with a New Parmaz-Schatz
      stent entrapped in the left main coronary artery (LMT) of a 65-year-old man. He
      underwent surgical removal of the stent with ascending aorta incision and double
      coronary artery bypass grafting (CABG) using saphenous veins. We believe that a
      stent entrapped in the LMT must be removed as rapidly as possible to avoid sudden
      death. Furthermore, in order to avoid the risk of peripheral thrombosis,
      retrieval is also the case in patients whose distal coronary flow can be
      maintained with CABG.

PMID- 9660917
TI  - The Mitochondrial F0F1-ATPase proton pump is required for function of the
      proapoptotic protein Bax in yeast and mammalian cells.
AB  - The proapoptotic mammalian protein Bax associates with mitochondrial membranes
      and confers a lethal phenotype when expressed in yeast. By generating Bax
      resistant mutant yeast and using classical complementation cloning methods,
      subunits of the mitochondrial F0F1-ATPase proton pump were determined to be
      critical for Bax-mediated killing in S. cerevisiae. A pharmacological inhibitor
      of the proton pump, oligomycin, also partially abrogated the cytotoxic actions of
      Bax in yeast. In mammalian cells, oligomycin also inhibited Bax-induced apoptosis
      and activation of cell death proteases. The findings imply that an intact F0F1
      ATPase in the inner membrane of mitochondria is necessary for optimal function of
      Bax in both yeast and mammalian cells.

PMID- 9660918
TI  - Bax inhibitor-1, a mammalian apoptosis suppressor identified by functional
      screening in yeast.
AB  - The mammalian proapoptotic protein Bax confers a lethal phenotype when expressed
      in yeast. By exploiting this phenotype, we have identified a novel human Bax
      inhibitor, BI-1. BI-1 is an evolutionarily conserved integral membrane protein
      containing multiple membrane-spanning segments and is predominantly localized to
      intracellular membranes, similar to Bcl-2 family proteins. Moreover, BI-1 can
      interact with Bcl-2 and Bcl-XL but Bax or Bak, as demonstrated by in vivo cross
      linking and coimmunoprecipitation studies. When overexpressed in mammalian cells,
      BI-1 suppressed apoptosis included by Bax, etoposide, staurosporine, and growth
      factor deprivation, but not by Fas (CD95). Conversely, BI-1 antisense induced
      apoptosis. BI-1 thus represents a new type of regulator of cell death pathways
      controlled by Bcl-2 and Bax.

PMID- 9660919
TI  - Involvement of Brca2 in DNA repair.
AB  - Abnormalities precipitated by a targeted truncation in the murine gene Brca2
      define its involvement in DNA repair. In culture, cells harboring truncated Brca2
      exhibit a proliferative impediment that worsens with successive passages. Arrest
      in the G1 and G2/M phases is accompanied by elevated p53 and p21 expression.
      Increased sensitivity to genotoxic agents, particularly ultraviolet light and
      methylmethanesulfonate, shows that Brca2 function is essential for the ability to
      survive DNA damage. But checkpoint activation and apoptotic mechanisms are
      largely unaffected, thereby implicating Brca2 in repair. This is substantiated by
      the spontaneous accumulation of chromosomal abnormalities, including breaks and
      aberrant chromatid exchanges. These findings define a function of Brca2 in DNA
      repair, whose loss precipitates replicative failure, mutagen sensitivity, and
      genetic instability reminiscent of Bloom syndrome and Fanconi anemia.

PMID- 9660920
TI  - Identification of a tRNA-specific nuclear export receptor.
AB  - In eukaryotes, tRNAs are synthesized in the nucleus and after several maturation
      steps exported to the cytoplasm. Here, we identify exportin-t as a specific
      mediator of tRNA export. It is a RanGTP-binding, importin beta-related factor
      with predominantly nuclear localization. It shuttles rapidly between nucleus and
      cytoplasm and interacts with nuclear pore complexes. Exportin-t binds tRNA
      directly and with high affinity. Its cellular concentration in Xenopus oocytes
      was found to be rate-limiting for export of all tRNAs tested, as judged by
      microinjection experiments. RanGTP regulates the substrate-exportin-t interaction
      such that tRNA can be preferentially bound in the nucleus and released in the
      cytoplasm.

PMID- 9660921
TI  - PKA and MPF-activated polo-like kinase regulate anaphase-promoting complex
      activity and mitosis progression.
AB  - Ubiquitin-mediated proteolysis is the key to cell cycle control. Anaphase
      promoting complex/cyclosome (APC) is a ubiquitin ligase that targets cyclin B and
      factors regulating sister chromatid separation for proteolysis by the proteasome
      and, consequently, regulates metaphase-anaphase transition and exit from mitosis.
      Here we report that Cdc2-cyclin B-activated Polo-like kinase (Plk) specifically
      phosphorylates at least three components of APC and activates APC to ubiquitinate
      cyclin B in the in vitro-reconstituted system. Conversely, protein kinase A (PKA)
      phosphorylates two subunits of APC but suppresses APC activity. PKA is superior
      to Plk in its regulation of APC, and Plk activity peaks whereas PKA activity is
      falling at metaphase. These results indicate that Plk and PKA regulate mitosis
      progression by controlling APC activity.

PMID- 9660922
TI  - Cell cycle-dependent duplication and bidirectional migration of SeqA-associated
      DNA-protein complexes in E. coli.
AB  - Using immunofluorescence microscopy, we have found that SeqA protein, a regulator
      of replication initiation, is localized as discrete fluorescent foci in E. coli
      wild-type cells. Surprisingly, SeqA foci were observed also in an oriC deletion
      mutant. Statistical analysis revealed that a SeqA focus is localized at midcell
      in newborn cells. The SeqA focus is duplicated and tethered at midcell until an
      FtsZ ring is formed. Subsequently, these foci migrate in opposite directions
      toward cell quarter sites and remain tethered there until the cell divides. The
      cell cycle-dependent bidirectional migration of SeqA-DNA complexes is quite
      different from the migration pattern of oriC Dna copies. MukB protein is required
      for correct localization of SeqA complexes by an unknown mechanism.

PMID- 9660923
TI  - Sequence-specific DNA binding by the S. shibatae TFIIB homolog, TFB, and its
      effect on promoter strength.
AB  - Previous studies have established that Archaea possess a homolog of the
      eukaryotic basal transcription factor TFIIB, termed TFB, that functions together
      with the archaeal TATA-binding protein (TBP) to direct transcription by RNA
      polymerase. Here, we analyze the strong S. shibatae viral (SSV) T6 promoter and
      show that the region of DNA immediately upstream of the TATA-like A box
      influences promoter strength. When placed upstream of the much weaker rRNA
      promoter, this sequence makes it as strong as the T6 promoter. By using a
      combination of approaches, we show that S. shibatae TFB mediates sequence
      specific interactions with DNA flanking the A box. Thus, sequence-specific DNA
      recognition by TFB and TBP are codeterminants of promoter strength in Archaea.

PMID- 9660924
TI  - T. brucei RNA editing: adenosine nucleotides inversely affect U-deletion and U
      insertion reactions at mRNA cleavage.
AB  - In the currently envisioned mechanism of trypanosome mitochondrial RNA editing, U
      insertion and U-deletion cycles begin with a common kind of gRNA-directed
      cleavage. However, natural, altered, and mutationally interconverted editing
      sites reveal that U-deletional cleavage is inefficient without and activated by
      ATP and ADP, while U-insertional cleavage shows completely reverse nucleotide
      effects. The adenosine nucleotides' effects appear to be allosteric and
      determined solely by sequences immediately adjacent to the anchor duplex. Both U
      deletional and U-insertional cleavages are reasonably active at physiological
      mitochondrial ATP concentration. Notably, ATP and ADP markedly stimulate complete
      U-deletion and inhibit U-insertion reactions, reflecting their effects on
      cleavage. These plus previous results suggest that U deletion and U insertion are
      remarkably distinct.

PMID- 9660925
TI  - Localization of glycolipids in membranes by in vivo labeling and neutron
      diffraction.
AB  - Evidence is accumulating for the lateral organization of cell membrane lipids and
      proteins in the context of sorting or intracellular signaling. So far, however,
      information has been lacking on the details of protein-lipid interactions in such
      aggregates. Purple membranes are patches made up of lipids and the protein
      bacteriorhodopsin in the plasma membrane of certain Archaea. Naturally
      crystalline, they provide a unique opportunity to study the structure of a
      natural membrane at submolecular resolution by diffraction methods. We present a
      direct structural determination of the glycolipids with respect to
      bacteriorhodopsin in these membranes. Deuterium labels incorporated in vivo into
      the sugar moieties of the major glycolipid were localized by neutron diffraction.
      The data suggest a role for specific aromatic residue-carbohydrate stacking
      interactions in the formation of the purple membrane crystalline patches.

PMID- 9660926
TI  - Tumor suppressor p16INK4A: determination of solution structure and analyses of
      its interaction with cyclin-dependent kinase 4.
AB  - The solution structure of the tumor suppressor p16INK4A has been determined by
      NMR, and important recognition regions of both cdk4 and p16INK4A have been
      identified. The tertiary structure of p16INK4A contains four helix-turn-helix
      motifs linked by three loops. Twelve tumorigenic mutants of p16INK4A have been
      constructed and analyzed for their structure and activity, and new mutants have
      been designed rationally. A fragment of 58 residues at the N terminus of cdk4
      important for p16INK4A binding has been identified. The importance of this region
      was further verified by mutational analysis of cdk4. These results and docking
      experiments have been used to assess possible modes of binding between p16INK4A
      and cdk4.

PMID- 9660927
TI  - Ribozyme catalysis from the major groove of group II intron domain 5.
AB  - The most highly conserved nucleotides in D5, an essential active site component
      of group II introns, consist of an AGC triad, of which the G is invariant. To
      understand how this G participates in catalysis, the mechanistic contribution of
      its functional groups was examined. We observed that the exocyclic amine of G
      participates in ground state interactions that stabilize D5 binding from the
      minor groove. In contrast, each major groove heteroatom of the critical G
      (specifically N7 or O6) is essential for chemistry. Thus, major groove atoms in
      an RNA helix can participate in catalysis, despite their presumed
      inaccessibility. N7 or O6 of the critical G could engage in critical tertiary
      interactions with the rest of the intron or they could, together with phosphate
      oxygens, serve as a binding site for catalytic metal ions.

PMID- 9660928
TI  - Structural basis for sequence-nonspecific recognition of 5'-capped mRNA by a cap
      modifying enzyme.
AB  - Sequence-nonspecific binding of RNA, recognition of a 7-methylguanosine 5' mRNA
      cap, and methylation of a nucleic acid backbone are three crucial and ubiquitous
      events in eukaryotic nucleic acid processing and function. These three events
      occur concurrently in the modification of vaccinia transcripts by the
      methyltransferase VP39. We report the crystal structure of a ternary complex
      comprising VP39, coenzyme product S-adenosylhomocysteine, and a 5' m7 G-capped,
      single-stranded RNA hexamer. This structure reveals a novel and general mechanism
      for sequence-non-specific recognition of the mRNA transcript in which the protein
      interacts solely with the sugar-phosphate backbone of a short, single-stranded
      RNA helix. This report represents the first direct and detailed view of a protein
      complexed with single-stranded RNA or 5'-capped mRNA.

PMID- 9660929
TI  - The function of multisite splicing enhancers.
AB  - Splicing enhancers are RNA sequences consisting of one or more binding sites
      (enhancer elements) for specific serine/arginine (SR)-rich proteins. When
      associated with these elements, SR proteins activate splicing by recruiting the
      splicing machinery to the adjacent intron through protein-protein interactions.
      Here, we show that the rate and efficiency of splicing increases linearly, rather
      than synergistically, as the number of identical or nonidentical enhancer
      elements present on pre-mRNA is increased. We conclude that only one splicing
      enhancer complex at a time is capable of interacting with the constitutive
      splicing machinery. Thus, the function of multisite enhancer elements to increase
      the probability of an interaction between the enhancer complex and the splicing
      machinery rather than to promote functional synergy.

PMID- 9660930
TI  - CDC16 controls initiation at chromosome replication origins.
AB  - The Cdc28p cyclin-dependent kinase is thought to both catalyze the onset of DNA
      replication and prevent rereplication by blocking the reassembly of initiation
      complexes at replication origins. Budding yeast with mutations in the CDC16 gene
      represent an exception to this model, because they rereplicate DNA despite being
      in a G2-like arrest with continually elevated Cdc28p kinase activity. We show, in
      contradiction to Pichler et al. (1997), that the extra DNA that accumulates in
      cdc16 mutants is largely chromosomal, as we originally reported. Two-dimensional
      DNA electrophoresis shows that cdc16 mutants reinitiate DNA synthesis from normal
      chromosome replication origins, and density transfer experiments show that
      multiple chromosomal locations are affected. Rereplication from origins requires
      both Cdc6p and Cdc46/Mcm5p, initiation proteins that had been thought to be
      inactivated by the Cdc28p kinase. These results establish that CDC16 is required
      to prevent inappropriate firing of replication origins.

PMID- 9660931
TI  - Terminal differentiation of human breast cancer through PPAR gamma.
AB  - We have previously demonstrated that PPAR gamma stimulates the terminal
      differentiation of adipocyte precursors when activated by synthetic ligands, such
      as the antidiabetic thiazolidinedione (TZD) drugs. We show here that PPAR gamma
      is expressed at significant levels in human primary and metastatic breast
      adenocarcinomas. Ligand activation of this receptor in cultured breast cancer
      cells causes extensive lipid accumulation, changes in breast epithelial gene
      expression associated with a more differentiated, less malignant state, and a
      reduction in growth rate and clonogenic capacity of the cells. Inhibition of MAP
      kinase, shown previously to be a powerful negative regulator of PPAR gamma,
      improves the TZD ligand sensitivity of nonresponsive cells. These data suggest
      that the PPAR gamma transcriptional pathway can induce terminal differentiation
      of malignant breast epithelial cells and thus may provide a novel, nontoxic
      therapy for human breast cancer.

PMID- 9660932
TI  - A new model for phenotypic suppression of frameshift mutations by mutant tRNAs.
AB  - According to the prevailing model, frameshift-suppressing tRNAs with an extra
      nucleotide in the anticodon loop suppress +1 frameshift mutations by recognizing
      a four-base codon and promoting quadruplet translocation. We present three sets
      of experiments that suggest a general alternative to this model. First, base
      modification should actually block such a four-base interaction by two classical
      frameshift suppressors. Second, for one Salmonella suppressor tRNA, it is not
      mutant tRNA but a structurally normal near cognate that causes the +1 shift in
      frame. Finally, frameshifting occurs in competition with normal decoding of the
      next in-frame codon, consistent with an event that occurs in the ribosomal P site
      after the translocation step. These results suggest an alternative model
      involving peptidyl-tRNA slippage at the classical CCC-N and GGG-N frameshift
      suppression sites.

PMID- 9660933
TI  - Structural alterations and conformational dynamics in Holliday junctions induced
      by binding of a site-specific recombinase.
AB  - Binding of a cleavage-incompetent mutant of the Flp recombinase induces a roughly
      square-planar geometry in synthetic immobile Holliday junctions. The branch
      points, which are rigidly fixed in these junctions in their free forms, tend to
      be more flexible in their protein-bound forms. Our results (1) suggest a
      plausible mechanism for the switching of the recombination complex from the
      Holliday-forming mode to the Holliday-resolving mode, (2) provide a rationale for
      previous observations that Flp resolves preformed immobile Holliday structures in
      the parental or in the recombinant mode in a relatively unbiased manner, and (3)
      accommodate two modes of DNA cleavage by Flp (transhorizontal or transdiagonal)
      in Holliday substrates.

PMID- 9660934
TI  - Absence of Gcn5 HAT activity defines a novel state in the opening of chromatin at
      the PHO5 promoter in yeast.
AB  - Histone acetyltransferase (HAT) activity has been demonstrated for several
      transcriptional activators, formally connecting chromatin modification with gene
      regulation. However, no effect on chromatin has been demonstrated. We have
      investigated the role of the HAT Gcn5 at the nucleosomally regulated PHO5
      promoter. Under conditions of constitutive submaximal activation (i.e., in the
      absence of the negative regulator Pho80), deletion of Gcn5 determines a novel
      randomized nucleosomal organization across the promoter and leads to a dramatic
      reduction in activity. Furthermore, mutation of amino acids critical for Gcn5 HAT
      activity is sufficient to generate this structure. This intermediate state in
      chromatin opening gives way to the fully open structure upon maximal induction
      (phosphate starvation), even in the absence of Gcn5. Thus, Gcn5 is shown to
      affect directly the remodeling of chromatin in vivo.

PMID- 9660935
TI  - Virus infection induces the assembly of coordinately activated transcription
      factors on the IFN-beta enhancer in vivo.
AB  - We have identified a virus-activated factor (VAF) that binds to a regulatory
      element shared by different virus-inducible genes. We provide evidence that VAF
      contains two members of the interferon regulatory factor (IRF) family of
      transcriptional activator proteins (IRF-3 and IRF-7), as well as the
      transcriptional coactivator proteins p300 and CBP. Remarkably, VAF, as well as
      recombinant IRF-3 and IRF-7 proteins, binds very weakly to the interferon-beta
      (IFN-beta) gene promoter in vitro. However, in virus-infected cells, both
      proteins are recruited to the endogenous IFN-beta promoter as part of a protein
      complex that includes ATF-2/c-Jun and NF-kappa B. These observations provide a
      unique example of the coordinate activation of multiple transcriptional activator
      proteins and their highly cooperative assembly into a transcriptional enhancer
      complex in vivo.

PMID- 9660936
TI  - Regulated chromosomal DNA replication in the absence of a nucleus.
AB  - Using Xenopus egg extracts, we have developed a completely soluble system for
      eukaryotic chromosomal DNA replication. In the absence of a nuclear envelope, a
      single, complete round of ORC-dependent DNA replication is catalyzed by cytosolic
      and nuclear extracts added sequentially to demembranated sperm chromatin or
      prokaryotic plasmid DNA. The absence of rereplication is explained by an activity
      present in the nucleus that prevents the binding of MCM to chromatin. Our results
      indicate that the role of the nuclear envelope in DNA replication is to
      concentrate activators and inhibitors of replication inside the nucleus. In
      addition, they provide direct evidence that metazoans use the same strategy as
      yeast to activate DNA replication and to restrict it to a single round per cell
      cycle.

PMID- 9660937
TI  - Structural features impose tight peptide binding specificity in the nonclassical
      MHC molecule HLA-E.
AB  - The crystal structure of the nonclassical human class lb MHC molecule HLA-E has
      been determined in complex with a prototypic ligand, the nonamer peptide
      (VMAPRTVLL), derived from the highly conserved residues 3-11 of the human MHC
      class la leader sequence. The mode of peptide binding retains some of the
      standard features observed in MHC class la complexes, but novel features imply
      that HLA-E has evolved to mediate specific binding to a tightly defined set of
      almost identical hydrophobic peptides from the highly conserved class l leader
      sequences. These molecular adaptations make HLA-E a rigorous checkpoint at the
      cell surface reporting on the integrity of the antigen processing pathway to
      CD94/NKG2 receptor-bearing natural killer cells.

PMID- 9660938
TI  - DNA damaging agents induce expression of Fas ligand and subsequent apoptosis in T
      lymphocytes via the activation of NF-kappa B and AP-1.
AB  - Apoptosis induced by DNA damage and other stresses can proceed via expression of
      Fas ligand (FasL) and ligation of its receptor, Fas (CD95). We report that
      activation of the two transcription factors NF-kappa B and AP-1 is crucially
      involved in FasL expression induced by etoposide, teniposide, and UV irradiation.
      A nondegradable mutant of I kappa B blocked both FasL expression and apoptosis
      induced by DNA damage but not Fas ligation. These stimuli also induced the stress
      activated kinase pathway (SAPK/JNK), which was required for the maximal induction
      of apoptosis. A 1.2 kb FasL promoter responded to DNA damage, as well as
      coexpression with p65 Rel or Fos/Jun. Mutations in the relevant NF-kappa B and AP
      1 binding sites eliminated these responses. Thus, activation of NF-kappa B and AP
      1 contributes to stress-induced apoptosis via the expression of FasL.

PMID- 9660939
TI  - Cleavage of p21Cip1/Waf1 and p27Kip1 mediates apoptosis in endothelial cells
      through activation of Cdk2: role of a caspase cascade.
AB  - Apoptosis of human endothelial cells after growth factor deprivation is
      associated with rapid and dramatic up-regulation of cyclin A-associated cyclin
      dependent kinase 2(cdk2) activity. In apoptotic cells, the C termini of the cdk
      inhibitors p21Cip1/Waf1 and p27Kip1 are truncated by specific cleavage. The
      enzyme involved in this cleavage is CPP32 and/or a CPP32-like caspase. After
      cleavage, p21Cip1/Waf1 loses its nuclear localization sequence and exits the
      nucleus. Cleavage of p21Cip1/Waf1 and p27Kip1 results in a substantial reduction
      in their association with nuclear cyclin-cdk2 complexes, leading to a dramatic
      induction of cdk2 activity. Dominant-negative cdk2, as well as a mutant of
      p21Cip1/Waf1 resistant to caspase cleavage, partially suppress apoptosis. These
      data suggest that cdk2 activation, through caspase-mediated cleavage of cdk
      inhibitors, may be instrumental in the execution of apoptosis following caspase
      activation.

PMID- 9660940
TI  - A novel human WD protein, h-beta TrCp, that interacts with HIV-1 Vpu connects CD4
      to the ER degradation pathway through an F-box motif.
AB  - HIV-1 Vpu interacts with CD4 in the endoplasmic reticulum and triggers CD4
      degradation, presumably by proteasomes. Human beta TrCP identified by interaction
      with Vpu connects CD4 to this proteolytic machinery, and CD4-Vpu-beta TrCP
      ternary complexes have been detected by coimmunoprecipitation. beta TrCP binding
      to Vpu and its recruitment to membranes require two phosphoserine residues in Vpu
      essential for CD4 degradation. In beta TrCP, WD repeats at the C terminus mediate
      binding to Vpu, and an F box near the N terminus is involved in interaction with
      Skp1p, a targeting factor for ubiquitin-mediated proteolysis. An F-box deletion
      mutant of beta TrCP had a dominant-negative effect on Vpu-mediated CD4
      degradation. These data suggest that beta TrCP and Skp1p represent components of
      a novel ER-associated protein degradation pathway that mediates CD4 proteolysis.

PMID- 9660941
TI  - Positionally cloned gene for a novel glomerular protein--nephrin--is mutated in
      congenital nephrotic syndrome.
AB  - Congenital nephrotic syndrome of the Finnish type (NPHS1) is an autosomal
      recessive disorder, characterized by massive proteinuria in utero and nephrosis
      at birth. In this study, the 150 kb critical region of NPHS1 was sequenced,
      revealing the presence of at least 11 genes, the structures of 5 of which were
      determined. Four different mutations segregating with the disease were found in
      one of the genes in NPHS1 patients. The NPHS1 gene product, termed nephrin, is a
      1241-residue putative transmembrane protein of the immunoglobulin family of cell
      adhesion molecules, which by Northern and in situ hybridization was shown to be
      specifically expressed in renal glomeruli. The results demonstrate a crucial role
      for this protein in the development or function of the kidney filtration barrier.

PMID- 9660942
TI  - GAA instability in Friedreich's Ataxia shares a common, DNA-directed and
      intraallelic mechanism with other trinucleotide diseases.
AB  - We show that GAA instability in Friedreich's Ataxia is a DNA-directed mutation
      caused by improper DNA structure at the repeat region. Unlike CAG or CGG repeats,
      which form hairpins, GAA repeats form a YRY triple helix containing non-Watson
      Crick pairs. As with hairpins, triplex mediates intergenerational instability in
      96% of transmissions. In families with Friedreich's Ataxia, the only recessive
      trinucleotide disease, GAA instability is not a function of the number of long
      alleles, ruling out homologous recombination or gene conversion as a major
      mechanism. The similarity of mutation pattern among triple repeat-related
      diseases indicates that all trinucleotide instability occurs by a common,
      intraallelic mechanism that depends on DNA structure. Secondary structure
      mediates instability by creating strong polymerase pause sites at or within the
      repeats, facilitating slippage or sister chromatid exchange.

PMID- 9660943
TI  - Transglutaminase action imitates Huntington's disease: selective polymerization
      of Huntingtin containing expanded polyglutamine.
AB  - Different proteins bearing polyglutamine of excessive length are lethal to
      neurons and cause human disease of the central nervous system. In parts of the
      brain affected by Huntington's disease, the amount of the huntingtin with
      expanded polyglutamine is reduced and there appear huntingtin-containing polymers
      of larger molecular weight. We show here that huntingtin is a substrate of
      transglutaminase in vitro and that the rate constant of the reaction increases
      with length of the polyglutamine over a range of an order of magnitude. As a
      result, huntingtin with expanded polyglutamine is preferentially incorporated
      into polymers. Both disappearance of the huntingtin with expanded polyglutamine
      and its replacement by polymeric forms are prevented by inhibitors of
      transglutaminase. The effect of transglutaminase therefore duplicates the changes
      in the affected parts of the brain.

PMID- 9660944
TI  - SOR1, a gene required for photosensitizer and singlet oxygen resistance in
      Cercospora fungi, is highly conserved in divergent organisms.
AB  - Filamentous Cercospora fungi are resistant to photosensitizing compounds that
      generate singlet oxygen. C. nicotianae photosensitizer-sensitive mutants were
      restored to full resistance by transformation with SOR1 (Singlet Oxygen
      Resistance 1), a gene recovered from a wild-type genomic library. SOR1 null
      mutants generated via targeted gene replacement confirmed the requirement for
      SOR1 in photosensitizer resistance. SOR1 RNA is present throughout the growth
      cycle. Although resistance to singlet oxygen is rare in biological systems, SOR1,
      a gene with demonstrated activity against singlet-oxygen-generating
      photosensitizers, is highly conserved in organisms from widely diverse taxa. The
      characterization of SOR1 provides an additional phenotype to this large group of
      evolutionarily conserved genes.

PMID- 9660945
TI  - Human Smad3 and Smad4 are sequence-specific transcription activators.
AB  - Mounting evidence indicates that Smad proteins are required for TGF beta
      signaling, but the way(s) in which Smad proteins propagate this signal is
      unclear. We found that two human Smad proteins (Smad3 and Smad4) could
      specifically recognize an identical 8 bp palindromic sequences (GTCTAGAC). Tandem
      repeats of this palindrome conferred striking TGF beta responsiveness to a
      minimal promoter. This responsiveness was abrogated by targeted deletion of the
      cellular Smad4 gene. These results define a novel biochemical property of Smad
      proteins that is likely to play a direct role in the biologic responses to TGF
      beta and related ligands.

PMID- 9660946
TI  - Identification of SOCS-3 as a potential mediator of central leptin resistance.
AB  - Leptin affects food intake and body weight by actions on the hypothalamus.
      Although leptin resistance is common in obesity, mechanisms have not been
      identified. We examined the effect of leptin on expression of the suppressors-of
      cytokine-signaling (SOCS) family of proteins. Peripheral leptin administration to
      ob/ob, but not db/db mice, rapidly induced SOCS-3 mRNA in hypothalamus, but had
      no effect on CIS, SOCS-1, or SOCS-2. A leptin-dependent increase of SOCS-3 mRNA
      was seen in areas of hypothalamus expressing high levels of the leptin receptor
      long form. In mammalian cell lines, SOCS-3, but not CIS or SOCS-2, blocked leptin
      induced signal transduction. Expression of SOCS-3 mRNA in the arcuate and
      dorsomedial hypothalamic nuclei is increased in Ay/a mice, a model of leptin
      resistant murine obesity. In conclusion, SOCS-3 is a leptin-inducible inhibitor
      of leptin signaling, and a potential mediator of leptin resistance in obesity.

PMID- 9660947
TI  - Selective inhibition of NFAT activation by a peptide spanning the calcineurin
      targeting site of NFAT.
AB  - NFAT transcription factors play a key role in the immune response. The activation
      of NFAT proteins is controlled by calcineurin, the calmodulin-dependent
      phosphatase that is inhibited by the immunosuppressive drugs cyclosporin A and
      FK506. Here we identify a short conserved sequence in NFAT proteins that targets
      calcineurin to NFAT. Mutation of a single residue in this sequence impairs the
      calcineurin-mediated dephosphorylation and nuclear translocation of NFAT1.
      Peptides spanning the region inhibit the ability of calcineurin to bind to and
      dephosphorylate NFAT proteins, without affecting the phosphatase activity of
      calcineurin against other substrates. When expressed intracellularly, a
      corresponding peptide inhibits NFAT dephosphorylation, nuclear translocation, and
      NFAT-mediated expression in response to stimulation. Thus, disruption of the
      enzyme-substrate docking interaction that directs calcineurin to NFAT can
      effectively block NFAT-dependent functions.

PMID- 9660948
TI  - Multiple effects of trehalose on protein folding in vitro and in vivo.
AB  - The disaccharide trehalose is produced in large quantities by diverse organisms
      during a variety of stresses. Trehalose prevents proteins from denaturing at high
      temperatures in vitro, but its function in stress tolerance in vivo is
      controversial. We report that trehalose stabilizes proteins in yeast cells during
      heat shock. Surprisingly, trehalose also suppresses the aggregation of denatured
      proteins, maintaining them in a partially-folded state from which they can be
      activated by molecular chaperones. The continued presence of trehalose, however,
      interferes with refolding, suggesting why it is rapidly hydrolyzed following heat
      shock. These findings reconcile conflicting reports on the role of trehalose in
      stress tolerance, provide a novel tool for accessing protein folding
      intermediates, and define new parameters for modulating stress tolerance and
      protein aggregation.

PMID- 9660949
TI  - TAP, the human homolog of Mex67p, mediates CTE-dependent RNA export from the
      nucleus.
AB  - The constitutive transport element (CTE) of the type D retroviruses promotes
      nuclear export of unspliced viral RNAs apparently by recruiting host factor(s)
      required for export of cellular messenger RNAs. Here, we report the
      identification of TAP as the cellular factor that specifically binds to wild-type
      CTE but not to export-deficient CTE mutants. Microinjection experiments performed
      in Xenopus oocytes demonstrate that TAP directly stimulates CTE-dependent export.
      Furthermore, TAP overcomes the mRNA export block caused by the presence of
      saturating amounts of CTE RNA. Thus, TAP, like its yeast homolog Mex67p, is a
      bona fide mRNA nuclear export mediator. TAP is the second cellular RNA binding
      protein shown to be directly involved in the export of its target RNA.

PMID- 9660950
TI  - Phosphorylation of NF-kappa B p65 by PKA stimulates transcriptional activity by
      promoting a novel bivalent interaction with the coactivator CBP/p300.
AB  - The transcriptional activity of NF-kappa B is stimulated upon phosphorylation of
      its p65 subunit on serine 276 by protein kinase A (PKA). The transcriptional
      coactivator CPB/p300 associates with NF-kappa B p65 through two sites, an N
      terminal domain that interacts with the C-terminal region of unphosphorylated
      p65, and a second domain that only interacts with p65 phosphorylated on serine
      276. Accessibility to both sites is blocked in unphosphorylated p65 through an
      intramolecular masking of the N terminus by the C-terminal region of p65.
      Phosphorylation by PKA both weakens the interaction between the N- and C-terminal
      regions of p65 and creates an additional site for interaction with CBP/p300.
      Therefore, PKA regulates the transcriptional activity of NF-kappa B by modulating
      its interaction with CBP/p300.

PMID- 9660951
TI  - The Xenopus dorsalizing factor Gremlin identifies a novel family of secreted
      proteins that antagonize BMP activities.
AB  - Using a Xenopus expression-cloning screen, we have isolated Gremlin, a novel
      antagonist of bone morphogenetic protein (BMP) signaling that is expressed in the
      neural crest. Gremlin belongs to a novel gene family that includes the head
      inducing factor Cerberus and the tumor suppressor DAN. We show that all family
      members are secreted proteins and that they act as BMP antagonists in embryonic
      explants. We also provide support for the model that Gremlin, Cerberus, and DAN
      block BMP signaling by binding BMPs, preventing them from interacting with their
      receptors. In addition, Cerberus alone blocks signaling by Activin- and Nodal
      like members of the TGF beta superfamily. Therefore, we propose that Gremlin,
      Cerberus, and DAN control diverse processes in growth and development by
      selectively antagonizing the activities of different subsets of the TGF beta
      ligands.

PMID- 9660952
TI  - Gametogenesis in yeast is regulated by a transcriptional cascade dependent on
      Ndt80.
AB  - Gametogenesis requires the successful coordination of two key processes, meiotic
      nuclear division and gamete morphogenesis. A central regulatory step in
      progression through gametogenesis occurs at the pachytene stage of meiotic
      prophase. We find that Ndt80 functions at pachytene of yeast gametogenesis
      (sporulation) to activate transcription of a set of genes required for both
      meiotic division (e.g., B-type cyclins) and gamete formation (e.g., SPS1).
      Ectopic synthesis of Ndt80 in vegetative cells induces transcription of these
      genes, and recombinant Ndt80 protein binds to a conserved sequence in their
      upstream region. Transcription of NDT80 itself is dependent on Ime1, which
      activates expression of early sporulation genes. Transcription of the Ndt80
      regulated gene CLB1 is mediated by the checkpoint gene RAD17. Thus Ndt80 is a
      pivotal component of a transcriptional cascade programming yeast gametogenesis
      and may also be a target of meiotic checkpoint control.

PMID- 9660953
TI  - Meiotic prophase arrest with failure of chromosome synapsis in mice deficient for
      Dmc1, a germline-specific RecA homolog.
AB  - DMC1 is a meiosis-specific gene first discovered in yeast that encodes a protein
      with homology to RecA and may be component of recombination nodules. Yeast dmc1
      mutants are defective in crossing over and synaptonemal complex (SC) formation,
      and arrest in late prophase of meiosis I. We have generated a null mutation in
      the Dmc1 gene in mice and show that homozygous mutant males and females are
      sterile with arrest of gametogenesis in the first meiotic prophase. Chromosomes
      in mutant spermatocytes fail to synapse, despite the formation of axial elements
      that are the precursor to the SC. The strong similarity of phenotypes in Dmc1
      deficient mice and yeast suggests that meiotic mechanisms have been highly
      conserved through evolution.

PMID- 9660954
TI  - The mouse RecA-like gene Dmc1 is required for homologous chromosome synapsis
      during meiosis.
AB  - The mouse Dmc1 gene is an E. coli RecA homolog that is specifically expressed in
      meiosis. The DMC1 protein was detected in leptotene-to-zygotene spermatocytes,
      when homolog pairing likely initiates. Targeted gene disruption in the male mouse
      showed an arrest of meiosis of germ cells at the early zygotene stage, followed
      by apoptosis. In female mice lacking the Dmc1 gene, normal differentiation of
      oogenesis was aborted in embryos, and germ cells disappeared in the adult ovary.
      Meiotic chromosome analysis of Dmc1-deficient mouse spermatocytes revealed random
      spread of univalent axial elements without correct pairing between homologs. In
      rare cases, however, we observed complex pairing among nonhomologs. Thus, the
      mouse Dmc1 gene is required for homologous synapsis of chromosomes in meiosis.

PMID- 9660955
TI  - Crystal structure of the N-terminal domain of sialoadhesin in complex with 3'
      sialyllactose at 1.85 A resolution.
AB  - The structure of the functional N-terminal domain from the extracellular region
      of the cell surface receptor sialoadhesin has been determined in complex with the
      oligosaccharide 3' sialyllactose. This provides structural information for the
      siglec family of proteins. The structure conforms to the V-set immunoglobulin
      like fold but contains several distinctive features, including an intra-beta
      sheet disulphide and a splitting of the standard beta strand G into two shorter
      strands. These novel features appear important in adapting the V-set fold for
      sialic acid-mediated recognition. Analysis of the complex with 3'sialyllactose
      highlights three residues, conserved throughout the siglec family, as key
      features of the sialic acid-binding template. The complex is representative of
      the functional recognition interaction with carbohydrate and as such provides
      detailed information for a heterotypic cell adhesion interaction.

PMID- 9660956
TI  - Unveiling two distinct ribonuclease activities and a topoisomerase activity in a
      site-specific DNA recombinase.
AB  - The site-specific DNA recombinase Flp shows two types of RNA cleavage activities
      on hybrid DNA-RNA substrates. One targets the phosphodiester position involved in
      DNA recombination and follows a related mechanistic path. In this two-step
      reaction, first-strand scission is mediated by a nucleophilic attack of the
      scissile phosphodiester bond by the active site tyrosine of Flp. The resultant 3'
      O-phosphoryl tyrosine bond is then attacked by the adjacent 2'-hydroxyl group.
      The second activity targets the immediately adjacent phosphodiester bond to the
      3' side using a distinct mechanism. In this reaction, the vicinal 2'-hydroxyl
      directly attacks the phosphate group in a manner that is reminiscent of the
      pancreatic RNase mechanism. The Flp protein can also be shown to possess a
      topoisomerase-like activity.

PMID- 9660957
TI  - Polynucleotide ligase activity of eukaryotic topoisomerase I.
AB  - Introduction of a single ribonucleoside immediately 5' of the scissile phosphate
      of a duplex DNA substrate converts eukaryotic topoisomerase I into an
      endoribonuclease. Here, I demonstrate that the RNase reaction is reversible.
      Vaccinia topoisomerase can ligate 2', 3'-cyclic phosphate and 5'-hydroxyl termini
      annealed to a bridging template strand. Remarkably, the ligase activity of
      topoisomerase does not require the active site tyrosine, implying that strand
      joining can occur via direct attack of the 5' hydroxyl on the cyclic phosphate
      without a covalent intermediate. Ligation does require other catalytic side
      chains on the enzyme. These findings underscore how a common ancestral mechanism
      of phosphoryl and nucleotidyl transfer can be harnessed to perform seemingly
      diverse tasks through subtle changes at the active site.

PMID- 9660958
TI  - DNA topoisomerase I and PC4 can interact with human TFIIIC to promote both
      accurate termination and transcription reinitiation by RNA polymerase III.
AB  - A human TFIIIC-containing complex (operationally designated holo TFIIIC) has been
      isolated by immunoaffinity methods and further resolved into two components that
      are both required for promoter-directed transcription of the VA1 gene. One
      component, designated TFIIIC, contains 5 polypeptides previously ascribed to
      TFIIIC2 and 4 additional polypeptides that correspond to TFIIIC1. Included within
      the other component are factors, namely DNA topoisomerase I and PC4, previously
      shown to serve as coactivators for transcription by RNA polymerase II.
      Topoisomerase I and PC4 both enhance TFIIIC interactions with down-stream
      promoter regions and promote multiple, but not single, round transcription by RNA
      polymerase III from preformed preinitiation complexes. Novel functions for holo
      TFIIIC in transcription elongation and accurate termination events that could be
      important for efficient reinitiation are also described.

PMID- 9660959
TI  - Unrestraining genetic processes with a protein-DNA hinge.
AB  - Genetic processes require direct interactions between proteins bound at
      nonadjacent cis elements. Because duplex DNA is rigid, either the protein-protein
      interactions are strong enough to deform the double helix or some feature of the
      intervening DNA must encourage juxtaposition of separated sites. For example,
      bent DNA can bring together only certain precisely positioned cis elements with
      the same helical phase. Interposing a DNA segment that both bends and twists
      easily to create a universal joint would provide an even more general mechanism
      to promote the association of separated sites regardless of position. A cis
      element of the human c-myc gene, known to be melted in vivo, and its associated
      single-strand DNA binding protein were examined and found to comprise just such a
      protein-DNA hinge.

PMID- 9660960
TI  - Arginine/serine-rich domains of SR proteins can function as activators of pre
      mRNA splicing.
AB  - Serine/arginine (SR)-rich splicing factors contain an RNA binding domain and an
      arginine/serine (RS)-rich domain required for protein-protein interactions. In
      addition to their roles in the basic splicing reaction, SR proteins function as
      components of splicing enhancer complexes. Here, we investigate the role of RS
      domains in splicing enhancer function. Hybrid proteins containing RS domains
      fused to the MS2 RNA binding protein were tested in vitro with RNA substrates
      bearing an MS2 recognition sequence. These hybrid proteins activated splicing in
      nuclear extracts, but not in S100 extracts lacking SR proteins. However, intact
      recombinant SR proteins could complement the activity of the hybrid proteins in
      S100 extracts. These data demonstrate that RS domains function as splicing
      activators and suggest that the general and enhancer-dependent functions of SR
      proteins can be uncoupled.

PMID- 9660961
TI  - FRA10B structure reveals common elements in repeat expansion and chromosomal
      fragile site genesis.
AB  - A common mechanism for chromosomal fragile site genesis is not yet apparent.
      Folate-sensitive fragile sites are expanded p(CCG)n repeats that arise from
      longer normal alleles. Distamycin A or bromodeoxyuridine-inducible fragile site
      FRA16B is an expanded AT-rich approximately 33 bp repeat; however, the
      relationship between normal and fragile site alleles is not known. Here, we
      report that bromodeoxyuridine-inducible, distamycin A-insensitive fragile site
      FRA10B is composed of expanded approximately 42 bp repeats. Differences in repeat
      motif length or composition between different FRA10B families indicate multiple
      independent expansion events. Some FRA10B alleles comprise a mixture of different
      expanded repeat motifs. FRA10B fragile site and long normal alleles share
      flanking polymorphisms. Somatic and intergenerational FRA10B repeat instability
      analogous to that found in expanded trinucleotide repeats supports dynamic
      mutation as a common mechanism for repeat expansion.

PMID- 9660962
TI  - XRCC2 and XRCC3, new human Rad51-family members, promote chromosome stability and
      protect against DNA cross-links and other damages.
AB  - The phenotypically similar hamster mutants irs1 and irs1SF exhibit high
      spontaneous chromosome instability and broad-spectrum mutagen sensitivity,
      including extreme sensitivity to DNA cross-linking agents. The human XRCC2 and
      XRCC3 genes, which functionally complement irs1 and irs1SF, respectively, were
      previously mapped in somatic cell hybrids. Characterization of these genes and
      sequence alignments reveal that XRCC2 and XRCC3 are members of an emerging family
      of Rad51-related proteins that likely participate in homologous recombination to
      maintain chromosome stability and repair DNA damage. XRCC3 is shown to interact
      directly with HsRad51, and like Rad55 and Rad57 in yeast, may cooperate with
      HsRad51 during recombinational repair. Analysis of the XRCC2 mutation in irs1
      implies that XRCC2's function is not essential for viability in cultured hamster
      cells.

PMID- 9660963
TI  - Alkyl hydroperoxide reductase subunit C (AhpC) protects bacterial and human cells
      against reactive nitrogen intermediates.
AB  - In Salmonella typhimurium, ahpC encodes subunit C of alkyl hydroperoxide
      reductase, an enzyme that reduces organic peroxides. Here, we asked if ahpC could
      protect cells from reactive nitrogen intermediates (RNI). Salmonella disrupted in
      ahpC became hypersusceptible to RNI. ahpC from either Mycobacterium tuberculosis
      or S. typhimurium fully complemented the defect. Unlike protection against cumene
      hydroperoxide, protection afforded by ahpC against RNI was independent of the
      reducing flavoprotein, AhpF. Mycobacterial ahpC protected human cells from
      necrosis and apoptosis caused by RNI delivered exogenously or produced
      endogenously by transfected nitric oxide synthase. Resistance to RNI appears to
      be a physiologic function of ahpC. ahpC is the most widely distributed gene known
      that protects cells directly from RNI, and provides an enzymatic defense against
      an element of antitubercular immunity.

PMID- 9660964
TI  - Osmotin, a plant antifungal protein, subverts signal transduction to enhance
      fungal cell susceptibility.
AB  - The plant pathogenesis-related protein osmotin is an antifungal cytotoxic agent
      that causes rapid cell death in the yeast S. cerevisiae. We show here that
      osmotin uses a signal transduction pathway to weaken defensive cell wall barriers
      and increase its cytotoxic efficacy. The pathway activated by osmotin includes
      the regulatory elements of the mating pheromone response STE4, STE18, STE20,
      STE5, STE11, STE7, FUS3, KSS1, and STE12. Neither the pheromone receptor nor its
      associated G protein alpha subunit GPA1 are required for osmotin action. However,
      mutation of SST2, a negative regulator of G alpha proteins, resulted in
      supersensitivity to osmotin. Phosphorylation of STE7 was rapidly stimulated by
      osmotin preceding any changes in cell vitality or morphology. These results
      demonstrate that osmotin subverts target cell signal transduction as part of its
      mechanism of action.

PMID- 9660965
TI  - The Tec29 tyrosine kinase is required during Drosophila embryogenesis and
      interacts with Src64 in ring canal development.
AB  - Tec29 encodes the only known Drosophila member of the Tec tyrosine kinases. By
      identifying the first mutations in Tec29 (formerly Src29A), we show that it is
      essential for head involution during embryogenesis and for ring canal development
      during oogenesis. Tec29 mutant egg chambers are defective in transfer of
      cytoplasm from the accessory nurse cells through the ring canals into the oocyte.
      Growth of the mutant ring canals is arrested, and they lack the strong
      phosphotyrosine localization seen in wild-type ring canals. Mutants lacking the
      Drosophila Src homolog Src64 show the same phenotype, and we show that Src64 is
      required for the localization of Tec29 to the ring canals. This interaction is
      similar to that between vertebrate Src and Tec kinases and suggests that Tec29 is
      an effector of Src64 that modifies ring canal components required for growth.

PMID- 9660966
TI  - SRC64 regulates the localization of a Tec-family kinase required for Drosophila
      ring canal growth.
AB  - Mutation of the Src64 gene of Drosophila results in ovarian ring canal defects
      and reduced female fertility. We used a dosage-sensitive modifier screen to
      search for downstream components of the SRC64 signaling pathway. We show that
      mutations affecting Tec29, an essential gene encoding a member of the Tec family
      of protein tyrosine kinases, dominantly enhance the Src64 ring canal phenotype.
      Loss of Tec29 function in the female germline results in a phenotype strikingly
      similar to that caused by the loss of Src64 function. In each case, the ring
      canals are reduced in size and phosphotyrosine content. We further demonstrate
      that TEC29 localizes to the ring canal, and this subcellular localization
      requires Src64 function. These data suggest that TEC29 is a downstream target of
      SRC64, and that regulating TEC29 localization during ring canal growth may be a
      crucial SRC64 function.

PMID- 9660967
TI  - Functional rescue of the sarcoglycan complex in the BIO 14.6 hamster using delta
      sarcoglycan gene transfer.
AB  - Four types of limb-girdle muscular dystrophy (LGMD) are known to be caused by
      mutations in distinct sarcoglycan genes. The BIO 14.6 hamster is a model for
      sarcoglycan-deficient LGMD with a deletion in the delta-sarcoglycan (delta-SG)
      gene. We investigated the function of the sarcoglycan complex and the feasibility
      of sarcoglycan gene transfer for LGMD using a recombinant delta-SG adenovirus in
      the BIO 14.6 hamster. We demonstrate extensive long-term expression of delta
      sarcoglycan and rescue of the entire sarcoglycan complex, as well as restored
      stable association of alpha-dystroglycan with the sarcolemma. Importantly, muscle
      fibers expressing delta-sarcoglycan lack morphological markers of muscular
      dystrophy and exhibit restored plasma membrane integrity. In summary, the
      sarcoglycan complex is requisite for the maintenance of sarcolemmal integrity,
      and primary mutations in individual sarcoglycan components can be corrected in
      vivo.

PMID- 9660968
TI  - Structural elements of an orphan nuclear receptor-DNA complex.
AB  - The nuclear hormone receptors form the largest known family of transcription
      factors. The current notion of receptor DNA discrimination, based solely on one
      major type of hexameric half-site and a highly conserved 66-residue core DNA
      binding domain (DBD), does not adequately describe how more than 150 nonsteroid
      receptors differentiate among response elements. Here, we describe the 2.3 A
      crystal structure of the DNA-binding region of the orphan receptor RevErb
      arranged as a tandem homodimer on its optimal response element. The structure
      reveals the presence of a second major protein-DNA interface adjacent to the
      classical one involving the half-sites. A sequence comparison of orphan receptors
      suggests that unique minor-groove interactions involving the receptor hinge
      regions impart the necessary DNA and dimerization specificity.

PMID- 9660969
TI  - The Pumilio RNA-binding domain is also a translational regulator.
AB  - Posterior patterning in the Drosophila embryo requires the action of Nanos (Nos)
      and Pumilio (Pum), which collaborate to regulate the translation of maternal
      hunchback (hb) mRNA. Previous work demonstrated that Pum recognizes sites in the
      3' UTR of hb mRNA. In this report, we first define the RNA-binding domain of Pum
      and then show that residues essential for translational repression are embedded
      within this domain. We also show that Nos and Pum can repress cap-independent
      translation from an internal ribosome entry site (IRES) in vivo, suggesting that
      they act downstream of the initial steps of normal, cap-dependent translation.

PMID- 9660970
TI  - Folding of the hairpin ribozyme in its natural conformation achieves close
      physical proximity of the loops.
AB  - The hairpin ribozyme is a self-cleaving motif found in the negatives strand of
      the satellite RNA of some plant viruses. In its natural context, the ribozyme
      comprises four helices, two of which contain conserved formally unpaired loops,
      that are adjacent arms of a four-way RNA junction. We show that the arms that
      would carry these loops are brought close together in the global conformation of
      the isolated junction. Using fluorescence resonance energy transfer, we
      demonstrate a two-magnesium ion-dependent conformational transition of the
      complete ribozyme that brings the loopbearing arms into close physical proximity.
      The ribozyme is active as a four-way junction, and the rate of cleavage may be
      modulated by the conformation of the four-way junction.

PMID- 9660971
TI  - Solution structure of a substrate for the archaeal pre-tRNA splicing
      endonucleases: the bulge-helix-bulge motif.
AB  - The structure of the bulge-helix-bulge motif that constitutes the intron/exon
      splice site in H. volcanii pre-tRNATrp has been determined by NMR spectroscopy.
      The conformations of the two 3 nt bulges, where the pre-tRNA is cleaved, are
      stabilized by stacking interactions between bulge nucleotides and bases in the
      adjacent Watson-Crick helices and by a network of backbone hydrogen bonds. Both
      bulges are presented on the same minor groove face of the central 4 bp helix, and
      the overall structure has approximate two-fold symmetry, which makes it well
      suited for attack by archaeal splicing endonucleases, which are symmetric dimers.

PMID- 9660972
TI  - An activator target in the RNA polymerase II holoenzyme.
AB  - Expression of protein-coding genes in eukaryotes involves the recruitment, by
      transcriptional activator proteins, of a transcription initiation apparatus
      consisting of greater than 50 polypeptides. Recent genetic and biochemical
      evidence in yeast suggests that a subset of these proteins, called SRB proteins,
      are likely targets for transcriptional activators. We demonstrate here, through
      affinity chromatography, photo-cross-linking, and surface plasmon resonance
      experiments, that the GAL4 activator interacts directly with the SRB4 subunit of
      the RNA polymerase II holoenzyme. The GAL4 activation domain binds to two
      essential segments of SRB4. The physiological relevance of this interaction is
      confirmed by mutations in SRB4, which occur within its GAL4-binding domain and
      which restore activation in vivo by a GAL4 derivative bearing a mutant activation
      domain.

PMID- 9660973
TI  - Functional analysis of the human TAFII250 N-terminal kinase domain.
AB  - The largest subunit of the human transcription factor TFIID, TAFII250, was
      previously reported to contain serine/threonine kinase domains that can
      autophosphorylate and transphosphorylate the large subunit of the basal factor
      TFIIF. Here, we identify the regions of the N-terminal kinase domain (amino acids
      1-414) necessary for kinase activity and examine its function in vivo. Point
      mutations within two patches of amino acids in the kinase domain decrease both
      autophosphorylation and transphosphorylation activities. Importantly, we find
      that TAFII250-bearing mutations within the N-terminal kinase domain exhibit a
      significantly reduced ability to rescue ts13 cells that express a temperature
      sensitive TAFII250. Moreover, transcription from the cyclin A and cdc2 promoters
      becomes impaired when cotransfected with hTAFII250 containing inactive forms of
      the N-terminal kinase domain. Our results suggest that the TAFII250 kinase
      activity is required to direct transcription of at least some genes in vivo.

PMID- 9660974
TI  - Activation of transcription in vitro by recruitment of the yeast RNA polymerase
      II holoenzyme.
AB  - It has been argued that many transcriptional activators work by "recruitment,"
      that is, by helping the transcriptional machinery bind stably to DNA. We
      demonstrate here a realization of a strong prediction of this idea in an in vitro
      transcription reaction performed with purified yeast RNA polymerase II holoenzyme
      and a classical transcriptional activator. We show that the level of
      transcription reached by the activator working on low concentrations of
      holoenzyme can also be reached in the absence of activator by raising the
      holoenzyme concentration, and that under that condition the activator has no
      further stimulatory effect. We also show, in agreement with another prediction of
      the recruitment model, that in a reaction using a holoenzyme purified from cells
      bearing the "P" mutation, transcription is stimulated by a DNA-tethered peptide
      that binds the mutant holoenzyme component Gal11P but that lacks a classical
      activating region.

PMID- 9660975
TI  - Activator-mediated recruitment of the RNA polymerase II machinery is the
      predominant mechanism for transcriptional activation in yeast.
AB  - Eukaryotic transcriptional activators bind to enhancer elements and stimulate the
      RNA polymerase II (pol II) machinery via functionally autonomous activation
      domains. In yeast cells, the normal requirement for an activation domain can be
      bypassed by artificially connecting an enhancer-bound protein to a component of
      the pol II machinery. This observation suggests, but does not necessarily
      indicate, that the physiological role of activation domains is to recruit the pol
      II apparatus to promoters. Here, we show that transcriptional stimulation does
      not occur when the activation domain is physically disconnected from the enhancer
      bound protein and transferred to components of the pol II machinery. The
      observation that autonomous activation domains are functional when connected to
      enhancer-bound proteins but not to components of the pol II machinery strongly
      argues that recruitment is the predominant mechanism for transcriptional
      activation in yeast.

PMID- 9660976
TI  - Transcription activation via enhanced preinitiation complex assembly in a human
      cell-free system lacking TAFIIs.
AB  - In contrast to previous findings in cell-free systems reconstituted with
      partially purified metazoan factors, we demonstrate dramatic activation of
      transcription in a TBP-dependent but TAFII-independent manner in HeLa nuclear
      extracts immunodepleted of TBP and major TAFIIs. Single-round transcription
      assays reveal that TAFII-independent activation is manifested at the level of
      productive preinitiation complex formation and that TAFIIs actually impair
      functional preinitiation complex assembly in a core promoter-specific manner.
      Furthermore, TAFIIs appear to elevate absolute levels of transcription under
      multiple-round transcription conditions, presumably by facilitating secondary
      initiation events. Finally, human coactivator activities related to those in
      yeast RNA polymerase II/mediator complexes appear to function in unfractionated
      HeLa nuclear extracts.

PMID- 9660977
TI  - Exocytosis of insulin promotes insulin gene transcription via the insulin
      receptor/PI-3 kinase/p70 s6 kinase and CaM kinase pathways.
AB  - The control of glucose homeostasis by insulin requires, in addition to the
      glucose-induced insulin release, a highly dynamic control of insulin
      biosynthesis. Although elevated glucose concentrations have been shown to trigger
      insulin biosynthesis at the levels of transcription and translation, the
      molecular mechanisms underlying the immediate transcriptional control are poorly
      understood. By investigating signal transduction pathways involved in the
      "glucose-dependent" transcriptional control, thereby analyzing endogenous
      (prepro)insulin mRNA levels and monitoring on-line insulin promoter-driven GFP
      expression, we provide, for the first time, evidence that physiologically
      stimulated insulin secretion from the pancreatic beta cell promotes insulin
      biosynthesis by enhancing insulin gene transcription in an autocrine manner. We
      show that secreted insulin acts via beta-cell insulin receptors and up-regulates
      insulin gene transcription by signaling through the IRS-2/PI-3 kinase/p70 s6k and
      CaM kinase pathways.

PMID- 9660978
TI  - Two-component signal transduction as a target for microbial anti-infective
      therapy.

PMID- 9660979
TI  - In vitro susceptibilities of 27 rickettsiae to 13 antimicrobials.
AB  - The MICs of 13 antibiotics (doxycycline, thiamphenicol, rifampin, amoxicillin,
      gentamicin, co-trimoxazole, ciprofloxacin, pefloxacin, ofloxacin, erythromycin,
      josamycin, clarithromycin, and pristinamycin) were determined for 27 available
      rickettsial species or strains. We used two in vitro cell culture methods
      described previously: the plaque assay and the microplaque colorimetric assay.
      Our results confirm the susceptibilities of rickettsiae to doxycycline,
      thiamphenicol, and fluoroquinolones. Beta-lactams, aminoglycosides, and
      cotrimoxazole were not active. Typhus group rickettsiae were susceptible to all
      macrolides tested, whereas the spotted fever group rickettsiae, R. bellii, and R.
      canada were more resistant, with josamycin, a safe alternative for the treatment
      of Mediterranean spotted fever, being the most effective compound. Strain Bar 29,
      R. massiliae, R. montana, R. aeschlimannii, and R. rhipicephali, which are
      members of the same phylogenetic subgroup, were more resistant to rifampin than
      the other rickettsiae tested. Heterogeneity in susceptibility to rifampin, which
      we report for the first time, may explain in vivo discrepancies in the
      effectiveness of this antibiotic for the treatment of rickettsial diseases. We
      hypothesize that rifampin resistance and erythromycin susceptibility may reflect
      a divergence during the evolution of rickettsiae.

PMID- 9660980
TI  - Selection and characterization of beta-lactam-beta-lactamase inactivator
      resistant mutants following PCR mutagenesis of the TEM-1 beta-lactamase gene.
AB  - Mechanism-based inactivators of beta-lactamases are used to overcome the
      resistance of clinical pathogens to beta-lactam antibiotics. This strategy can
      itself be overcome by mutations of the beta-lactamase that compromise the
      effectiveness of their inactivation. We used PCR mutagenesis of the TEM-1 beta
      lactamase gene and sequenced the genes of 20 mutants that grew in the presence of
      ampicillin-clavulanate. Eleven different mutant genes from these strains
      contained from 1 to 10 mutations. Each had a replacement of one of the four
      residues, Met69, Ser130, Arg244, and Asn276, whose substitutions by themselves
      had been shown to result in inhibitor resistance. None of the mutant enzymes with
      multiple amino acid substitutions generated in this study conferred higher levels
      of resistance to ampicillin alone or ampicillin with beta-lactamase inactivators
      (clavulanate, sulbactam, or tazobactam) than the levels of resistance conferred
      by the corresponding single-mutant enzymes. Of the four enzymes with just a
      single mutation (Ser130Gly, Arg244Cys, Arg244Ser, or Asn276Asp), the Asn276Asp
      beta-lactamase conferred a wild-type level of ampicillin resistance and the
      highest levels of resistance to ampicillin in the presence of inhibitors. Site
      directed random mutagenesis of the Ser130 codon yielded no other mutant with
      replacement of Ser130 besides Ser130Gly that produced ampicillin-clavulanate
      resistance. Thus, despite PCR mutagenesis we found no new mutant TEM beta
      lactamase that conferred a level of resistance to ampicillin plus inactivators
      greater than that produced by the single-mutation enzymes that have already been
      reported in clinical isolates. Although this is reassuring, one must caution that
      other combinations of multiple mutations might still produce unexpected
      resistance.

PMID- 9660981
TI  - Antimicrobial therapies for Helicobacter pylori infection in gnotobiotic piglets.
AB  - Gnotobiotic piglets infected with Helicobacter pylori were treated with various
      antimicrobials as monotherapy and dual therapy, and the results were compared to
      those for piglets treated with a triple-therapy regimen (bismuth subsalicyclate
      at 5.7 mg/kg of body weight, metronidazole at 4.4 mg/kg, and amoxicillin at 6.8
      mg/kg four times a day [QID]). Clearance of infection was assessed after 7 days
      of treatment, and eradication was assessed following 7 days of treatment and a 14
      day posttreatment observation interval. Monotherapy with amoxicillin,
      clarithromycin, and ciprofloxacin cleared and eradicated the organism from
      porcine stomachs; monotherapy with metronidazole cleared the infection and
      eradicated it from some piglets. Metronidazole-resistant microbes were recovered
      from treated piglets which cleared but did not eradicate the infection.
      Monotherapy with bismuth subsalicylate, erythromycin, nitrofurantoin, and
      tetracycline in the dosage range of 5.0 to 7.1 mg/kg QID was less than 100%
      effective in clearance and eradication, in that these drugs cleared and/or
      eradicated the infection from some of the piglets but did not eradicate the
      infection from all of the piglets. Monotherapy with an H-2 receptor antagonist
      (ranitidine) or a proton pump inhibitor (omeprazole) was ineffective at either
      clearance or eradication. In vivo dose titrations with several effective
      monotherapies were performed to determine the lowest effective in vivo dose of
      drug. In piglets, eradication was associated with a statistically significant
      decline in serum H. pylori-specific immunoglobulin M (IgM) antibodies; the titers
      of both IgA and IgG also declined, but the values were not statistically
      significant. For many antimicrobials, piglets are more sensitive indicators of
      clearance and eradication than humans. These data establish the H. pylori
      infected gnotobiotic piglet as a useful model for the identification of novel
      antimicrobials for the treatment of this disease and for drug assessment during
      preclinical evaluations.

PMID- 9660982
TI  - Famciclovir and valaciclovir differ in the prevention of herpes simplex virus
      type 1 latency in mice: a quantitative study.
AB  - Famciclovir (FCV) and valaciclovir (VACV) have previously been shown to be potent
      inhibitors of herpes simplex virus type 1 (HSV-1) in a murine cutaneous model. In
      the present study, mice were inoculated in the skin of the left ear pinna with
      herpes simplex virus (HSV) type 1. Antiviral therapy was started on different
      days postinoculation (p.i.), terminating at the end of day 10 p.i. The compounds
      were administered twice daily by oral gavage at 50 mg/kg of body weight/dose.
      Mice were sampled on day 5 p.i., during the acute phase of the infection, and the
      titers of infectious virus in the target tissues (ear, brain stem, and trigeminal
      ganglia) were determined. At 2 to 3 months p.i., the ipsilateral and
      contralateral trigeminal and cervical dorsal root ganglia were explanted, and
      four different methods were used to detect latent HSV. The methods were (i)
      conventional explant culture for 5 days followed by homogenization, (ii) long
      term culture (up to 73 days) of whole ganglia, followed by homogenization, (iii)
      dissociation by enzymatic disaggregation and an infectious center assay, and (iv)
      in situ hybridization to detect latency-associated transcripts (LATs). The
      conventional explant culture method was the least sensitive method, while in situ
      staining for LAT was the most sensitive, and all mice, including those treated
      from early times with FCV, were shown to be latently infected. Significantly less
      latent virus was detected by all four methods, however, in ganglia obtained from
      mice that had been treated with FCV in comparison with the amount detected in
      ganglia from mice that had been treated with VACV. However, in no case was
      latency completely eliminated.

PMID- 9660983
TI  - Chloramphenicol resistance in Clostridium difficile is encoded on Tn4453
      transposons that are closely related to Tn4451 from Clostridium perfringens.
AB  - The chloramphenicol resistance gene catD from Clostridium difficile was shown to
      be encoded on the transposons Tn4453a and Tn4453b, which were structurally and
      functionally related to Tn4451 from Clostridium perfringens. Tn4453a and Tn4453b
      excised precisely from recombinant plasmids, generating a circular form, as is
      the case for Tn4451. Evidence that this process is mediated by Tn4453-encoded
      tnpX genes was obtained from experiments which showed that in trans these genes
      complemented a Tn4451tnpX delta 1 mutation for excision. Nucleotide sequencing
      showed that the joint of the circular form generated by the excision of Tn4453a
      and Tn4453b was similar to that from Tn4451. These results suggest that the
      Tn4453-encoded TnpX proteins bind to similar DNA target sequences and function in
      a manner comparable to that of TnpX from Tn4453. Furthermore, it has been shown
      that Tn4453a and Tn4453b can be transferred to suitable recipient cells by RP4
      and therefore are mobilizable transposons. It is concluded that, like Tn4451,
      they must encode a functional tnpZ gene and a target oriT or RSA site. The
      finding that related transposable elements are present in C. difficile and C.
      perfringens has implications for the evolution and dissemination of antibiotic
      resistance genes and the mobile elements on which they are found within the
      clostridia.

PMID- 9660984
TI  - Antiretroviral efficacy and pharmacokinetics of oral
      bis(isopropyloxycarbonyloxymethyl)-9-(2-phosphonylmethoxypropyl)adenine in mice.
AB  - To overcome the low oral bioavailability of the highly potent and selective
      antiretroviral agent (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA), a new
      lipophilic ester derivative, i.e., the bis(isopropyloxycarbonyloxymethyl)-ester
      [bis(POC)-PMPA], was prepared. The usefulness of bis(POC)-PMPA as an oral prodrug
      for PMPA was investigated in the intestinal mucosa Caco-2 cell monolayer model.
      The total transport of bis(POC)-PMPA was 2.7%, whereas it was less than 0.1% for
      PMPA. Bis(POC)-PMPA was considerably metabolized inside the epithelial cells,
      since the majority of the compound was recovered after transport in the form of
      the monoester metabolite [mono(POC)-PMPA]. In contrast, bis(POC)-PMPA was
      relatively resistant to degradation at the luminal side of the Caco-2 cells.
      Pharmacokinetic studies with mice showed that the oral bioavailability of
      bis(POC)-PMPA (calculated from the curves of the concentration of free PMPA in
      plasma) was 20%. Neither bis(POC)-PMPA nor mono(POC)-PMPA could be recovered in
      plasma, suggesting the efficient release of the active drug PMPA after oral
      administration of bis(POC)-PMPA. Severe combined immunodeficient (SCID) mice
      infected with Moloney murine sarcoma virus (MSV) and treated orally with bis(POC)
      PMPA for 5 or 10 days (dosages, 50, 100, or 200 mg of PMPA equivalent per kg of
      body weight per day) showed a significant delay in MSV-induced tumor appearance
      and tumor-associated death. The antiviral efficacy of oral bis(POC)-PMPA was
      related to the dosage and treatment period and was not significantly different
      from that of subcutaneous PMPA given at an equivalent dose. The favorable
      pharmacokinetic profile, marked antiviral efficacy, and low toxicity make
      bis(POC)-PMPA an attractive oral prodrug of PMPA that should be further pursued
      in clinical studies with patients infected with human immunodeficiency virus or
      hepatitis B virus.

PMID- 9660985
TI  - In vitro activities of co-amoxiclav at concentrations achieved in human serum
      against the resistant subpopulation of heteroresistant Staphylococcus aureus: a
      controlled study with vancomycin.
AB  - The effects of concentrations that simulated those in human serum after a single
      intravenous dose of amoxicillin (2 g), amoxicillin-clavulanic acid (2,000 and 200
      mg, respectively), or vancomycin (500 mg), on the viability and beta-lactamase
      activity of two isogenic (beta-lactamase and non-beta-lactamase producer)
      heteroresistant Staphylococcus aureus strains were studied in an in vitro
      pharmacodynamic model. A reduction of > or = 97% of the initial inoculum was
      obtained with vancomycin and amoxicillin-clavulanic acid against both strains,
      with respect to the total bacterial population and the oxacillin-resistant
      subpopulation. The same pattern was observed with amoxicillin and the beta
      lactamase-negative strain. beta-Lactamase activity in the beta-lactamase-positive
      strain changed over time parallel to viability, decreasing with amoxicillin
      clavulanic acid or vancomycin and increasing in the amoxicillin and control
      groups. Clavulanic acid concentrations achievable in serum that changed over time
      allowed amoxicillin to act against the beta-lactamase-producing methicillin
      resistant S. aureus to a similar extent as vancomycin.

PMID- 9660986
TI  - Oral cimetidine prolongs clarithromycin absorption.
AB  - The present study was conducted to identify any potential interaction between
      oral cimetidine and clarithromycin. Twelve healthy subjects were administered
      single doses of clarithromycin alone and with oral cimetidine dosed to steady
      state. Cimetidine prolonged the absorption of clarithromycin, as evidenced by
      decreased peak concentrations of both clarithromycin and 14-OH-clarithromycin
      (14OHC) in serum (46 and 43%, respectively), a delay in the formation of 14OHC
      (increase of 68%), and increases in both of their half-lives (75 and 82%,
      respectively), despite no changes in total oral clearance or area under the
      concentration-time curve for either compound. No mechanism for this interaction
      has been identified.

PMID- 9660987
TI  - Decreased accumulation or increased isoleucyl-tRNA synthetase activity confers
      resistance to the cyclic beta-amino acid BAY 10-8888 in Candida albicans and
      Candida tropicalis.
AB  - BAY 10-8888, a cyclic beta-amino acid, exerts its antifungal activity by
      inhibition of isoleucyl-tRNA synthetase activity after accumulation to a
      millimolar concentration inside the cell. We have selected and characterized BAY
      10-8888-resistant Candida albicans mutants. Reduced BAY 10-8888 accumulation as
      well as increased isoleucyl-tRNA synthetase activity was observed in these
      mutants. Some of the mutants were cross-resistant to cispentacin, a structurally
      related beta-amino acid, while sensitivities to 5-fluorocytosine and fluconazole
      remained unchanged in all mutants. All except two in vitro-resistant mutants were
      pathogenic in a murine candidiasis model, and BAY 10-8888 failed to cure the
      infection. Furthermore, we have characterized BAY 10-8888 transport and isoleucyl
      tRNA synthetase activity in several Candida tropicalis strains which showed MICs
      higher than those of other Candida strains. An analysis of the C. tropicalis
      strains revealed that intracellular concentrations of BAY 10-8888 were in the
      millimolar range, comparable to those for C. albicans. However, these isolates
      expressed isoleucyl-tRNA synthetase activities about fourfold higher than those
      for C. albicans. To test the possibility of resistance modeling, we determined
      the correlations between the intracellular concentration of BAY 10-8888, the
      specific activity of isoleucyl-tRNA synthetase, the number of free, i.e.,
      noninhibited, isoleucyl-tRNA synthetase molecules/cell, and growth, assuming a
      linear relation. We found significant correlations between growth and the
      intracellular concentration of BAY 10-8888 and between growth and the number of
      free isoleucyl-tRNA synthetase molecules/cell, but not between growth and the
      specific activity of isoleucyl-tRNA synthetase.

PMID- 9660988
TI  - Inhibition of hyphal growth of azole-resistant strains of Candida albicans by
      triazole antifungal agents in the presence of lactoferrin-related compounds.
AB  - The effects of bovine lactoferrin (LF) or the LF-derived antimicrobial peptide
      lactoferricin B (LFcin B) on the growth of Candida albicans hyphae, including
      those of three azole-resistant strains, were investigated by a crystal violet
      staining method. The hyphae of two highly azole-resistant strains were more
      susceptible to inhibition by LF or LFcin B than the azole-susceptible strains
      tested. One moderately azole-resistant strain was defective in the formation of
      hyphae and showed a susceptibility to LF greater than that of the susceptible
      strains but a susceptibility to LFcin B similar to that of the susceptible
      strains. The highly azole-resistant strain TIMM3317 showed trailing growth in the
      presence of fluconazole or itraconazole, while the extent of growth was reduced
      by the addition of LF or LFcin B at a sub-MIC. Thus, the addition of LF or LFcin
      B at a sub-MIC resulted in a substantial decrease in the MICs of fluconazole and
      itraconazole for two highly azole-resistant strains; e.g., the MIC of fluconazole
      for TIMM3317 was shifted from > 256 to 0.25 micrograms/ml by LF, but the MICs
      were not decreased for the susceptible strains. The combination effects observed
      with triazoles and LF-related compounds in the case of the two highly azole
      resistant strains were confirmed to be synergistic by the fractional inhibitory
      concentration index. These results demonstrate that for some azole-resistant C.
      albicans strains, LF-related compounds combined with triazoles can inhibit the
      growth of hyphae, an important form of this organism in pathogenesis.

PMID- 9660989
TI  - Glucuronidation of 3'-azido-3'-deoxythymidine (zidovudine) by human liver
      microsomes: relevance to clinical pharmacokinetic interactions with atovaquone,
      fluconazole, methadone, and valproic acid.
AB  - Zidovudine (3'-azido-3'-deoxythymidine [AZT]), an antiviral nucleoside analog
      effective in the treatment of human immunodeficiency virus infection, is
      primarily metabolized to an inactive glucuronide form, GAZT, via uridine-5'
      diphospho-glucuronosyltransferase (UGT) enzymes. UGT enzymes exist as different
      isoforms, each exhibiting substrate specificity. Published clinical studies have
      shown that atovaquone, fluconazole, methadone, and valproic acid decreased GAZT
      formation, presumably due to UGT inhibition. The effect of these drugs on AZT
      glucuronidation was assessed in vitro by using human hepatic microsomes to begin
      understanding in vitro-in vivo correlations for UGT metabolism. The
      concentrations of each drug studied were equal to those reported with the usual
      clinical doses and at concentrations at least 10 times higher than would be
      expected with these doses. High-performance liquid chromatography was used to
      assess the respective metabolism and formation of AZT and GAZT. All four drugs
      exhibited concentration-dependent inhibition of AZT glucuronidation. The
      respective concentrations of atovaquone and methadone which caused 50% inhibition
      of GAZT were > 100 and 8 micrograms/ml, well above their usual clinical
      concentrations. Fluconazole and valproic acid exhibited 50% inhibition of GAZT at
      50 and 100 micrograms/ml, which are within the clinical ranges of 10 to 100 and
      50 to 100 micrograms/ml, respectively. These data suggest that inhibition of AZT
      glucuronidation may be more clinically significant with concomitant fluconazole
      and valproic acid. Factors such as inter- and intraindividual pharmacokinetic
      variability and changes in AZT intracellular concentrations should be considered
      as other mechanisms responsible for changes in AZT pharmacokinetics with
      concomitant therapies.

PMID- 9660990
TI  - Pharmacokinetic evaluation of amphotericin B in lung tissue: lung lymph
      distribution after intravenous injection and airspace distribution after
      aerosolization and inhalation of amphotericin B.
AB  - We have studied the pharmacokinetics of amphotericin B (AmB) in lung lymph
      circulation and bronchial-wash fluid after intravenous infusion and inhalation,
      respectively. For two experiments with awake sheep, we used lung lymph fistulas
      and tracheotomy. In experiment 1, AmB concentrations in plasma and lung lymph
      after intravenous infusion of AmB (1 mg/kg of body weight) over 1.5 h were
      measured. The mean peak in plasma level was 756.0 +/- 188.8 ng/ml at 3 h after
      the start of infusion, and the level then decreased gradually to 194.8 +/- 28.9
      ng/ml at 24 h. The stable and maximal levels in lung lymph last 5 to 9 h after
      the start of AmB infusion. The concentrations in lung lymph after 9 h were
      slightly higher than those in plasma. Thus, the lung lymph-to-plasma ratio of AmB
      concentrations increased gradually during infusion, and the ratio was more than
      1.0 after the end of infusion, suggesting that AmB could be easily moved from
      plasma to pulmonary interstitium and/or lung lymph circulation. In another
      experiment, 5 or 30 mg of aerosol AmB was inhaled, and the concentration of AmB
      in the bronchial-wash fluid was determined by bronchoalveolar lavage. The peak
      AmB concentration in the fluid was observed at 0.5 h. After that, AmB was slowly
      eliminated over 24 h. The area under the concentration-time curve for 30 mg of
      inhaled AmB was higher than that for 5 mg, but maximum concentrations of AmB in
      serum for 5 and 30 mg were almost similar. These observations identify the
      pharmacokinetic characteristics of AmB in the lung and may provide a new insight
      into the strategy for clinical treatment of fungal pneumonia.

PMID- 9660991
TI  - Antifungal susceptibilities of Paecilomyces species.
AB  - The MICs and minimum fungicidal concentrations (MFCs) of amphotericin B,
      miconazole, itraconazole, ketoconazole, fluconazole, and flucytosine for 52
      isolates of Paecilomyces species were evaluated by the broth microdilution
      method, largely based on the recommendations of the National Committee for
      Clinical Laboratory Standards (document M27-A). The fungal isolates tested
      included 16 P. variotii, 11 P. lilacinus, 9 P. marquandii, 6 P. fumosoroseus, 4
      P. javanicus, and 2 P. viridis isolates and 1 isolate of each of the following
      species: P. carneus, P. farinosus, P. fulvus, and P. niveus. The MFCs and the
      MICs at which 90% of isolates were inhibited (MIC90s) for the six antifungal
      agents were remarkably high; the MIC50s indicated that amphotericin B,
      miconazole, itraconazole, and ketoconazole had good activities, while fluconazole
      and flucytosine demonstrated poor efficacy. The ranges of the MICs were generally
      wider and lower than those of the MFCs. There were significant susceptibility
      differences among the species. All species with the exception of P. variotii were
      highly resistant to fluconazole and flucytosine; P. variotii was susceptible to
      flucytosine. Amphotericin B and the rest of the azoles showed good activity
      against P. variotii, while all the antifungal agents assayed showed low efficacy
      against P. lilacinus.

PMID- 9660992
TI  - Erythromycin inhibits tumor necrosis factor alpha and interleukin 6 production
      induced by heat-killed Streptococcus pneumoniae in whole blood.
AB  - To determine the effects of penicillin and erythromycin on cytokine production
      induced by heat-killed Streptococcus pneumoniae (HKSP), we studied the effects of
      those drugs on cytokine production induced by S. pneumoniae in human whole blood
      in vitro and ex vivo. In whole blood in vitro, erythromycin, but not penicillin,
      caused a dose-dependent decrease in HKSP-induced production of tumor necrosis
      factor alpha (TNF) and interleukin 6 (IL-6), while the production of IL-10, IL
      12, and gamma interferon was inhibited only at the highest erythromycin
      concentration tested (10(-3) M). The production of TNF and IL-6 in whole blood
      obtained from healthy subjects after a 30-min infusion of erythromycin (1,000 mg)
      was lower after ex vivo stimulation with HKSP than that in blood drawn before the
      infusion. Inhibition of TNF contributed to erythromycin-induced inhibition of IL
      6 synthesis. Inhibition of TNF and IL-6 production by erythromycin may have a
      negative impact on host defense mechanisms during pneumococcal pneumonia.

PMID- 9660993
TI  - Cefepime-aztreonam: a unique double beta-lactam combination for Pseudomonas
      aeruginosa.
AB  - An in vitro pharmacokinetic model was used to determine if aztreonam could
      enhance the pharmacodynamics of cefepime or ceftazidime against an isogenic panel
      of Pseudomonas aeruginosa 164, including wild-type (WT), partially derepressed
      (PD), and fully derepressed (FD) phenotypes. Logarithmic-phase cultures were
      exposed to peak concentrations achieved in serum with 1- or 2-g intravenous
      doses, elimination pharmacokinetics were simulated, and viable bacterial counts
      were measured over three 8-h dosing intervals. In studies with cefepime and
      cefepime-aztreonam against the PD strain, samples were also filter sterilized,
      assayed for active cefepime, and assayed for nitrocefin hydrolysis activity
      before and after overnight dialysis. Against WT strains, the cefepime-aztreonam
      combination was the most active regimen, but viable counts at 24 h were only 1
      log below those in cefepime-treated cultures. Against PD and FD strains, the
      antibacterial activity of cefepime-aztreonam was significantly enhanced over that
      of each drug alone, with 3.5 logs of killing by 24 h. Hydrolysis and bioassay
      studies demonstrated that aztreonam was inhibiting the extracellular
      cephalosporinase that had accumulated and was thus protecting cefepime in the
      extracellular environment. In contrast to cefepime-aztreonam, the
      pharmacodynamics of ceftazidime-aztreonam were not enhanced over those of
      aztreonam alone. Further pharmacodynamic studies with five other P. aeruginosa
      strains producing increased levels of cephalosporinase demonstrated that the
      enhanced pharmacodynamics of cefepime-aztreonam were not unique to the isogenic
      panel. The results of these studies demonstrate that aztreonam can enhance the
      antibacterial activity of cefepime against derepressed mutants of P. aeruginosa
      producing increased levels of cephalosporinase. This positive interaction appears
      to be due in part to the ability of aztreonam to protect cefepime from
      extracellular cephalosporinase inactivation. Clinical evaluation of this
      combination is warranted.

PMID- 9660994
TI  - Genotypic and phenotypic characterization of human immunodeficiency virus type 1
      variants isolated from AIDS patients after prolonged adefovir dipivoxil therapy.
AB  - Adefovir dipivoxil [bis(pivaloyloxymethyl)-ester prodrug], an orally bioavailable
      prodrug of adefovir [9-(2-phosphonylmethoxyethyl)adenine], is currently in phase
      III clinical trials for the treatment of human immunodeficiency virus (HIV). In
      vitro experiments demonstrated that either a K65R or a K70E mutation in HIV
      reverse transcriptase (RT) was selected in the presence of adefovir, conferring a
      16- or 9-fold decrease in susceptibility to adefovir, respectively. Previous data
      demonstrated that patients receiving adefovir dipivoxil monotherapy (125 mg
      daily) for 12 weeks experienced a median decrease in HIV RNA levels of 0.5 log10
      copies/ml and that resistance to adefovir dipivoxil did not arise during that
      period. In the present investigation, a further study was undertaken to
      investigate whether RT mutations developed among viruses from patients who
      completed the 12-week study and who opted to enroll in a maintenance phase of
      prolonged (6- to 12-month) adefovir dipivoxil therapy (120 mg daily). Concomitant
      treatment with antiretroviral agents was permitted during the maintenance phase.
      The median decreases in HIV RNA levels for patients who completed 6 or 12 months
      of maintenance-phase dosing were 0.6 and 1.14 log10 copies/ml, respectively. The
      reductions in the HIV RNA levels were similar among patients who received
      adefovir dipivoxil with or without concomitant treatment with antiretroviral
      agents. Viruses from 8 of 29 patients dosed for up to 12 months developed RT
      mutations that were not present at baseline; these mutations may have been
      related to adefovir dipivoxil therapy. Viruses from two of the eight patients
      developed the K70E mutation while the patients were on therapy, but none of the
      viruses from patients developed the K65R RT substitution. Despite the development
      of RT mutations, sustained reductions (6 to 12 months) in viral load (> or = 0.7
      log10 copies/ml decrease from baseline) were observed in all eight patients.

PMID- 9660995
TI  - Antiviral activity of a selective ribonucleotide reductase inhibitor against
      acyclovir-resistant herpes simplex virus type 1 in vivo.
AB  - The present study reports the activity of BILD 1633 SE against acyclovir (ACV)
      resistant herpes simplex virus (HSV) infections in athymic nude (nu/nu) mice.
      BILD 1633 SE is a novel peptidomimetic inhibitor of HSV ribonucleotide reductase
      (RR). In vitro, it is more potent than ACV against several strains of wild-type
      as well as ACV-resistant HSV mutants. Its in vivo activity was tested against
      cutaneous viral infections in athymic nude mice infected with the ACV-resistant
      isolates HSV type 1 (HSV-1) dlsptk and PAAr5, which contain mutations in the
      viral thymidine kinase gene and the polymerase gene, respectively. Following
      cutaneous infection of athymic nude mice, both HSV-1 dlsptk and PAAr5 induced
      significant, reproducible, and persistent cutaneous lesions that lasted for more
      than 2 weeks. A 10-day treatment regimen with ACV given topically four times a
      day as a 5% cream or orally at up to 5 mg/ml in drinking water was partially
      effective against HSV-1 PAAr5 infection with a reduction of the area under the
      concentration-time curve (AUC) of 34 to 48%. The effects of ACV against HSV-1
      dlsptk infection were not significant when it was administered topically and were
      only marginal when it was given in drinking water. Treatment under identical
      conditions with 5% topical BILD 1633 SE significantly reduced the cutaneous
      lesions caused by both HSV-1 dlsptk and PAAr5 infections. The effect of BILD 1633
      SE against HSV-1 PAAr5 infections was more prominent and was inoculum and dose
      dependent, with AUC reductions of 96 and 67% against infections with 10(6) and
      10(7) PFU per inoculation site, respectively. BILD 1633 SE also significantly
      decreased the lesions caused by HSV-1 dlsptk infection (28 to 51% AUC reduction).
      Combination therapy with topical BILD 1633 SE (5%) and ACV in drinking water (5
      mg/ml) produced an antiviral effect against HSV-1 dlsptk and PAAr5 infections
      that was more than the sum of the effects of both drugs. This is the first report
      that a selective HSV RR subunit association inhibitor can be effective against
      ACV-resistant HSV infections in vivo.

PMID- 9660996
TI  - Outer membrane profiles of clonally related Klebsiella pneumoniae isolates from
      clinical samples and activities of cephalosporins and carbapenems.
AB  - Fifteen isolates of Klebsiella pneumoniae producing extended-spectrum beta
      lactamases (ESBLs) isolated during a nosocomial outbreak were studied. The
      strains belonged to the same clonal type, as shown by pulsed-field gel
      electrophoretic analysis of chromosomal DNA. All the isolates were resistant to
      extended-spectrum cephalosporins, aztreonam, gentamicin, and fluoroquinolones and
      were susceptible to carbapenems, tobramycin, netilmicin, and amikacin. None of
      the isolates expressed the OmpK36 porin. Eight isolates, for which the MICs of
      cefoxitin were > or = 64 micrograms/ml, showed a diminished level or no
      expression of a 35-kDa porin. The MICs of meropenem, cefotaxime, and cefpirome
      were three to eight times higher for porin-deficient isolates than for isolates
      expressing the 35-kDa porin, but the MICs of imipenem increased two times for
      porin-deficient isolates compared to those for isolates expressing the porin.
      This MIC increase reverted to a level similar to that for the parental strain
      when porin-deficient isolates were transformed with the gene coding for the K.
      pneumoniae porin OmpK36. It is concluded that the high level of resistance to
      cefoxitin and the increase in the MICs of meropenem, cefotaxime, and cefpirome
      for the ESBL-producing K. pneumoniae isolates studied are associated with porin
      deficiency.

PMID- 9660997
TI  - In vitro and in vivo activities of levofloxacin against biofilm-producing
      Pseudomonas aeruginosa.
AB  - Interactions between biofilm cells of Pseudomonas aeruginosa and levofloxacin
      were studied. P. aeruginosa incubated for 6 days with Teflon sheets formed a
      biofilm on its surface. Against the biofilm bacteria, levofloxacin at an MIC
      determined by the standard method for the strain was highly bactericidal whereas
      gentamicin, ceftazidime, and ciprofloxacin showed no significant killing
      activity. Levofloxacin, ciprofloxacin, and gentamicin, but not ceftazidime,
      exhibited killing activity against nongrowing cells of the strain incubated in
      phosphate buffer. In addition, levofloxacin, ciprofloxacin, and ceftazidime, but
      not gentamicin, showed the ability to penetrate an agar containing alginate.
      These findings may explain the efficacy of levofloxacin and the ineffectiveness
      of gentamicin and ceftazidime against biofilm bacteria; however, the cause of the
      ineffectiveness of ciprofloxacin still remains to be determined. In experimental
      pneumonia in guinea pigs, in which the biofilm mode of growth of the strain was
      observed in the lung, only levofloxacin exhibited substantial therapeutic
      efficacy. These findings suggest the significant role of levofloxacin in therapy
      of biofilm bacterium-associated infectious diseases.

PMID- 9660998
TI  - Differences in the lipoprotein distribution of free and liposome-associated all
      trans-retinoic acid in human, dog, and rat plasma are due to variations in
      lipoprotein lipid and protein content.
AB  - The objective of the proposed study was to determine the distribution in plasma
      lipoprotein of free all-trans retinoic acid (ATRA) and liposomal ATRA (Atragen;
      composed of dimyristoyl phosphatidylcholine and soybean oil) following incubation
      in human, rat, and dog plasma. When ATRA and Atragen at concentrations of 1, 5,
      10, and 25 micrograms/ml were incubated in human and rat plasma for 5, 60, and
      180 min, the majority of the tretinoin was recovered in the lipoprotein-deficient
      plasma fraction. However, when ATRA and Afragen were incubated in dog plasma, the
      majority of the tretinoin (> 40%) was recovered in the high-density lipoprotein
      (HDL) fraction. No differences in the plasma distribution between ATRA and
      Atragen were found. These data suggest that a significant percentage of tretinoin
      associates with plasma lipoproteins (primarily the HDL fraction) upon incubation
      in human, dog, and rat plasma. Differences between the lipoprotein lipid and
      protein profiles in human plasma and in dog and rat plasma influenced the plasma
      distribution of ATRA and Atragen. Differences in lipoprotein distribution between
      ATRA and Atragen were not observed, suggesting that the drug's distribution in
      plasma in not influenced by its incorporation into these liposomes.

PMID- 9660999
TI  - Zidovudine azido-reductase in human liver microsomes: activation by ethacrynic
      acid, dipyridamole, and indomethacin and inhibition by human immunodeficiency
      virus protease inhibitors.
AB  - AZT (zidovudine, 3'-azido-3'-deoxythymidine), although metabolized primarily to
      AZT-glucuronide, is also metabolized to 3'-amino-3'-deoxythmidine (AMT) by
      reduction of the azide to an amine. The formation of the myelotoxic metabolite
      AMT has not been well characterized, but inhibition of AMT formation would be of
      therapeutic benefit. The aim of this study was to identify compounds that inhibit
      AMT formation. Using human liver microsomes under anaerobic conditions and [2
      14C]AZT, K(m) values of AZT azido-reductase, estimated by radio-thin-layer
      chromatography, were 2.2 to 3.5 mM (n = 3). Oxygen completely inhibited this
      NADPH-dependent reduction. Thirteen of the 28 compounds tested inhibited the
      formation of AMT. In addition to the CYP3A4 inhibitors ketoconazole, fluconazole,
      indinavir, ritonavir, and saquinavir, metyrapone strongly inhibited AMT
      formation. An unexpected finding was the more-than-twofold increase in AMT
      formation in the presence of ethacrynic acid, dipyridamole, or indomethacin. Such
      activation of toxic metabolite formation would impair drug therapy.

PMID- 9661000
TI  - Urinary excretion and bactericidal activities of a single oral dose of 400
      milligrams of fleroxacin versus a single oral dose of 800 milligrams of
      pefloxacin in healthy volunteers.
AB  - Twelve healthy volunteers participated in this randomized crossover study to
      compare the concentrations and recovery levels of fleroxacin and pefloxacin in
      urine and to assess their bactericidal activities against 12 strains of urinary
      pathogens with different susceptibilities over a wide range of MICs. The
      volunteers received a single oral dose of 400 mg of fleroxacin or 800 mg of
      pefloxacin. The mean cumulative renal excretion of unchanged fleroxacin, N
      demethyl-fleroxacin, and N-oxide-fleroxacin accounted for 67, 7, and 6% of the
      total dose, respectively. The total urinary recovery of pefloxacin and the active
      metabolite norfloxacin was 34%. In the time-kill and the urinary bactericidal
      titer (UBT) studies, only the subjects' urine not supplemented with broth was
      used. With most tested organisms and both quinolones it took more than 8 h to
      achieve a reduction in CFU of 99.9% (3 log units). Overall, there was a good
      correlation between UBTs and MICs for the strains. Against Escherichia coli ATCC
      25922 the median UBTs were similar for both antibiotics and at least 1:8 for 96
      h; against the E. coli strain for which the MIC was 0.5 microgram/ml the UBT was
      at least 1:4 for 48 h. The UBTs of both drugs against Klebsiella pneumoniae were
      at least 1:16 for 72 h. The UBTs for Staphylococcus aureus (the MIC for which was
      16 micrograms/ml) of both antibiotics were low, and in some of the samples, no
      bactericidal titers were observed. UBTs for Proteus mirabilis of pefloxacin are
      significantly higher than those of fleroxacin. For Pseudomonas aeruginosa the
      median UBTs were present for the 24-to-48-h interval. The same is true for
      Enterococcus faecalis. Against Staphylococcus saprophyticus, UBTs were present
      for at least 48 h with both quinolones. Overall, a single oral dose of 400 mg of
      fleroxacin exhibits UBTs comparable to those of 800 mg of pefloxacin. Therefore,
      it may be expected that half of the dose of fleroxacin gives comparable results
      in the treatment of urinary tract infections; this should be substantiated in
      comparative clinical trials.

PMID- 9661001
TI  - Antiherpesvirus activities of (1'S,2'R)-9-[[1',2'-bis(hydroxymethyl)cycloprop-1'
      yl]methyl]guanine (A-5021) in cell culture.
AB  - Antiherpetic activity of (1'S,2'R)-9-([1',2'-bis(hydroxymethyl)cycloprop
      1'yl]methyl)guanine (A-5021) was compared with those of acyclovir (ACV) and
      penciclovir (PCV) in cell cultures. In a plaque reduction assay using a selection
      of human cells, A-5021 showed the most potent activity in all cells. Against
      clinical isolates of herpes simplex virus type 1 (HSV-1, n = 5) and type 2 (HSV
      2, n = 6), mean 50% inhibitory concentrations (IC50s) for A-5021 were 0.013 and
      0.15 microgram/ml, respectively, in MRC-5 cells. Corresponding IC50s for ACV were
      0.22 and 0.30 microgram/ml, and those for PCV were 0.84 and 1.5 micrograms/ml,
      respectively. Against clinical isolates of varicella-zoster virus (VZV, n = 5),
      mean IC50s for A-5021, ACV, and PCV were 0.77, 5.2, and 14 micrograms/ml,
      respectively, in human embryonic lung (HEL) cells. A-5021 showed considerably
      more prolonged antiviral activity than ACV when infected cells were treated for a
      short time. The selectivity index, the ratio of 50% cytotoxic concentration to
      IC50, of A-5021 was superior to those of ACV and PCV for HSV-1 and almost
      comparable for HSV-2 and VZV. In a growth inhibition assay of murine granulocyte
      macrophage progenitor cells, A-5021 showed the least inhibitory effect of the
      three compounds. These results show that A-5021 is a potent and selective
      antiviral agent against HSV-1, HSV-2, and VZV.

PMID- 9661002
TI  - Ceftazidime-resistant Klebsiella pneumoniae and Escherichia coli isolates
      producing TEM-10 and TEM-43 beta-lactamases from St. Louis, Missouri.
AB  - Ceftazidime-resistant Escherichia coli and Klebsiella pneumoniae (49 and 102
      isolates, respectively) were collected from Barnes-Jewish Hospital, St. Louis,
      Mo., from 1992 to 1996. They were uniformly resistant to ceftazidime, generally
      resistant to aztreonam, and variably susceptible to cefotaxime. Four
      representative E. coli strains and 15 Klebsiella strains were examined. From one
      to four beta-lactamases were produced per strain, with three possible enzymes
      related to ceftazidime resistance: enzymes with pI values of 5.6, 6.1, or 7.6. By
      pulsed-field gel electrophoresis there were at least 13 different Klebsiella
      strain types and 3 different E. coli strain types, indicating that the outbreak
      was not clonal. After cloning and sequencing of the beta-lactamase-encoding
      genes, the enzyme with a pI of 5.6 was identified as TEM-10. The enzyme with a pI
      of 6.1 was a novel TEM variant (TEM-43) with Lys at 104, His at 164, and Thr at
      182. TEM-43 showed broad-spectrum hydrolytic activity against all penicillins,
      with the highest hydrolysis rate for ceftazidime compared to those for the other
      expanded-spectrum cephalosporins. Aztreonam was also a good substrate for TEM-43,
      with hydrolytic activity similar to that of ceftazidime and affinity higher than
      that of ceftazidime. The TEM-43 beta-lactamase was well inhibited by clavulanic
      acid and tazobactam at concentrations of < 10 nM. Sulbactam was less effective
      than the other inhibitors. The Thr182 mutation previously reported in an
      inhibitor-resistant beta-lactamase did not cause the TEM-43 enzyme to become
      resistant to any of the inhibitors.

PMID- 9661003
TI  - Administration of liposomal agents and blood clearance capacity of the
      mononuclear phagocyte system.
AB  - As liposomes are cleared from the circulation to a substantial extent by the
      phagocytic cells of the mononuclear phagocyte system (MPS), there is a question
      whether administration of liposome-based therapeutic agents interferes with
      clearance of infectious organisms by the MPS from blood. In the present study, at
      first the effect of administration of three types of empty liposomes (devoid of
      drug), differing in blood residence time, on carbon clearance and bacterial
      clearance from blood was studied with mice. Classical liposomes (LIP A) and
      placebo liposomes with lipid composition as in AmBisome (LIP B) or as in Doxil
      (LIP C) were used. Liposomes were administered intravenously as a single dose.
      Second, the effect of multiple-dose administration of AmBisome on bacterial blood
      clearance was studied with rats. AmBisome was administered with two different
      dosage schedules. The blood clearance capacity of the MPS was monitored at
      different time points after the last liposome injection. It was shown that the
      carbon blood clearance capacity of the MPS was impaired only at a high lipid dose
      of empty classical liposomes. The bacterial blood clearance capacity was never
      impaired, not even after prolonged treatment with AmBisome administered in a
      clinically relevant regimen.

PMID- 9661004
TI  - Contribution of outer membrane efflux protein OprM to antibiotic resistance in
      Pseudomonas aeruginosa independent of MexAB.
AB  - A Pseudomonas aeruginosa strain carrying an insertion of an omega Hg interposon
      in the mexB gene (mexB::omega Hg; strain K879) produced markedly reduced but
      still detectable levels of OprM, the product of the third gene of the mexAB-oprM
      multidrug efflux operon. By using a lacZ transcriptional fusion vector, promoter
      activity likely responsible for OprM expression in the mexB::omega Hg mutant was
      identified upstream of oprM. Introduction of the oprM gene, but not the mexAB
      genes, into a P. aeruginosa multidrug-susceptible delta mexAB-oprM mutant
      increased resistance to quinolones, cephalosporins, erythromycin, and
      tetracycline. A delta mexAB-oprM strain carrying the oprM gene accumulated
      markedly less antibiotic than the deletion strain without oprM. Antibiotic
      accumulation by the MexAB- OprM+ strain was markedly enhanced upon treatment of
      cells with the uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP),
      indicating that MexAB-independent OprM function likely involves an efflux
      process. Moreover, pretreatment of cells with CCCP prior to the accumulation
      assay abrogated any differences in accumulation levels between the MexAB- OprM+
      and MexAB- OprM- strains, indicating that reduced drug accumulation by the OprM+
      strain (in the absence of CCCP) cannot be due to OprM-mediated reduction in outer
      membrane permeability. It appears, therefore, the OprM can be expressed and
      function in a drug efflux capacity independent of MexAB.

PMID- 9661005
TI  - Gene amplification in Leishmania tarentolae selected for resistance to sodium
      stibogluconate.
AB  - Leishmania tarentolae promastigotes were selected step by step for resistance to
      sodium stibogluconate (Pentostam). Mutants resistant to antimony-containing drugs
      and cross-resistant to arsenite were therefore obtained. Amplification of one
      common locus was observed in several independent sodium stibogluconate-resistant
      mutants, and the locus amplified was novel. The copy number of the amplified
      locus was related to the level of resistance to pentavalent antimony. The gene
      responsible for antimony resistance was isolated by transfection and was shown to
      correspond to an open reading frame coding for 770 amino acids. The putative gene
      product did not exhibit significant homology with sequences present in data
      banks, and the putative role of this protein in antimony resistance is discussed.

PMID- 9661007
TI  - 16S rRNA mutation associated with tetracycline resistance in a gram-positive
      bacterium.
AB  - A genetic basis for tetracycline resistance in cutaneous propionibacteria was
      suggested by comparing the nucleotide sequences of the 16S rRNA genes from 16
      susceptible and 21 resistant clinical isolates and 6 laboratory-selected
      tetracycline-resistant mutants of a susceptible strain. Fifteen clinical isolates
      resistant to tetracycline were found to have cytosine instead of guanine at a
      position cognate with Escherichia coli 16S rRNA base 1058 in a region important
      for peptide chain termination and translational accuracy known as helix 34.
      Cytosine at base 1058 was not detected in the laboratory mutants or the
      tetracycline-susceptible strains. The apparent mutation was recreated by site
      directed mutagenesis in the cloned E. coli ribosomal operon, rrnB, encoded by
      pKK3535.E. coli strains carrying the mutant plasmid were more resistant to
      tetracycline than those carrying the wild-type plasmid both in MIC determinations
      and when grown in tetracycline-containing liquid medium. These data are
      consistent with a role for the single 16S rRNA base mutation in clinical
      tetracycline resistance in cutaneous propionibacteria.

PMID- 9661006
TI  - Fluconazole resistance associated with drug efflux and increased transcription of
      a drug transporter gene, PDH1, in Candida glabrata.
AB  - Sequential Candida glabrata isolates were obtained from the mouth of a patient
      infected with human immunodeficiency virus type 1 who was receiving high doses of
      fluconazole for oropharyngeal thrush. Fluconazole-susceptible colonies were
      replaced by resistant colonies that exhibited both increased fluconazole efflux
      and increased transcripts of a gene which codes for a protein with 72.5% identity
      to Pdr5p, an ABC multidrug transporter in Saccharomyces cerevisiae. The deduced
      protein had a molecular mass of 175 kDa and was composed of two homologous
      halves, each with six putative transmembrane domains and highly conserved
      sequences of ATP-binding domains. When the earliest and most azole-susceptible
      isolate of C. glabrata from this patient was exposed to fluconazole, increased
      transcripts of the PDR5 homolog appeared, linking azole exposure to regulation of
      this gene.

PMID- 9661008
TI  - Evaluation of moxifloxacin, a new 8-methoxyquinolone, for treatment of meningitis
      caused by a penicillin-resistant pneumococcus in rabbits.
AB  - Moxifloxacin is a new 8-methoxyquinolone with high activity against gram-positive
      bacteria, including penicillin-resistant pneumococci. In an experimental
      meningitis model, we studied the pharmacokinetics of moxifloxacin in infected and
      uninfected rabbits and evaluated the antibiotic efficacies of moxifloxacin,
      ceftriaxone, and vancomycin against a penicillin-resistant Streptococcus
      pneumoniae strain (penicillin, ceftriaxone, vancomycin, and moxifloxacin MICs
      were 1, 0.5, 0.5, and 0.125 microgram/ml, respectively). Moxifloxacin entered
      cerebrospinal fluid (CSF) readily, with peak values within 15 to 30 min after
      bolus intravenous infusion and with a mean percent penetration into normal and
      purulent CSF of approximately 50 and 80%, respectively. The bactericidal effect
      of moxifloxacin was concentration dependent, and regrowth was seen only when the
      concentration of moxifloxacin in CSF was below the minimal bactericidal
      concentration. All antibiotic-treated groups (moxifloxacin given in two doses of
      40 mg/kg of body weight, moxifloxacin in two 20-mg/kg doses, ceftriaxone in one
      125-mg/kg dose, and vancomycin in two 20-mg/kg doses) had significantly higher
      reductions in CSF bacterial concentration than the untreated group (P < 0.05).
      Moxifloxacin was as effective as vancomycin and ceftriaxone in reducing bacterial
      counts at all time points tested (3, 5, 10, and 24 h). Moreover, moxifloxacin
      given in two 40-mg/kg doses resulted in a significantly higher reduction in CSF
      bacterial concentration (in log10 CFU per milliliter) than vancomycin within 3 h
      after the start of antibiotic treatment (3.49 [2.94 to 4.78] versus 2.50 [0.30 to
      3.05]; P < 0.05). These results indicate that moxifloxacin could be useful in the
      treatment of meningitis, including penicillin-resistant pneumococcal meningitis.

PMID- 9661009
TI  - Effect of trovafloxacin on production of cytokines by human monocytes.
AB  - Antibiotics have previously been shown to have immunomodulatory effects. We
      examined the effect of the broad-spectrum fluoroquinoline antibiotic
      trovafloxacin on cytokine synthesis by monocytes obtained from healthy human
      volunteers and stimulated with either lipopolysaccharide or gram-positive cells
      (heat-killed Staphylococcus aureus [Pansorbin]). Trovafloxacin levels achievable
      in humans suppressed in vitro synthesis of each of the cytokines analyzed, viz.,
      interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, IL-10, granulocyte-macrophage
      colony-stimulating factor, and tumor necrosis factor alpha. This effect was not
      due to direct effects of the drug on cellular viability; at these concentrations,
      trovafloxacin did not have demonstrable cytotoxicity for the monocytes, as
      determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide
      (MTT) assay. Although similar patterns of suppression of cytokine synthesis were
      observed in samples obtained from the same volunteers on different days, there
      were significant day-to-day variations. These results reveal that trovafloxacin
      possesses significant immunomodulatory activity in vitro and suggest that
      suppression of acute-phase inflammatory responses may occur in vivo, elicited
      through trovafloxacin's effect on cytokine synthesis by human monocytes.

PMID- 9661010
TI  - Pharmacokinetic study of an oral cephalosporin, cefdinir, in hemodialysis
      patients.
AB  - The pharmacokinetics of cefdinir were investigated in six hemodialysis patients.
      For the present study, two tests were carried out, one with 4 h of hemodialysis
      and the other without hemodialysis. Cefdinir was given orally to each patient in
      a dose of 100 mg, and blood was collected serially for 48 h after dosing in the
      test without dialysis and for 72 h in the test with dialysis. In the test without
      dialysis, the maximum plasma concentration (Cmax) was 2.36 +/- 0.53 micrograms/ml
      (mean +/- standard deviation) and the time to Cmax was 9.00 +/- 2.45 h. The
      terminal elimination half-life (t1/2) and area under the concentration-time curve
      (AUC) were 16.95 +/- 1.20 h and 69.05 +/- 14.84 micrograms.h/ml, respectively. In
      the test with dialysis, t1/2 during hemodialysis decreased approximately to one
      sixth of that obtained in the test without dialysis, although t1/2 in the latter
      elimination phase did not differ from that in the nondialysis test. AUC was
      reduced to 43% of that in the test without dialysis. The fractional removal of
      cefdinir by hemodialysis was 61%. These findings indicate that clearance of
      cefdinir is prolonged in patients with renal failure, and cefdinir is well
      removed by introduction of hemodialysis, although t1/2 (during hemodialysis) and
      AUC were two and eight times higher than the data previously reported for healthy
      volunteers, respectively. The pharmacokinetic data suggest that 100 mg of oral
      cefdinir once a day would result in a sufficient concentration in plasma in
      hemodialysis patients, but this remains to be confirmed by multiple-dose studies.

PMID- 9661011
TI  - Efficacy of NS-718, a novel lipid nanosphere-encapsulated amphotericin B, against
      Cryptococcus neoformans.
AB  - In vitro and in vivo efficacies of NS-718, a lipid nanosphere-encapsulated
      amphotericin B (AMPH-B), have been studied. Of the tested AMPH-B formulations, NS
      718 had the lowest MIC for Cryptococcus neoformans. In a murine model, low-dose
      therapy (0.8 mg/kg of body weight) with NS-718 showed higher efficacy than that
      with AmBisome. High-dose therapy (2.0 mg/kg) with NS-718 was much more effective
      than those with Fungizone and AmBisome. In mice treated with a high dose of NS
      718, only a few yeast cells had grown in lung by 7 days after inoculation. A
      pharmacokinetic study showed higher concentrations of AMPH-B in lung following
      administration of NS-718 than after administration of AmBisome. Our results
      indicated that NS-718, a new AMPH-B formulation, is a promising antifungal agent
      for treatment of pulmonary cryptococcosis and could be the most effective
      antifungal agent against C. neoformans infections.

PMID- 9661012
TI  - Susceptibility of Chlamydia trachomatis to chlorhexidine gluconate gel.
AB  - To identify topical antimicrobial preparations which may be effective in
      preventing the transmission of sexually transmitted diseases, we examined the
      activity of chlorhexidine gluconate (CHG) against Chlamydia trachomatis.
      Chlamydial elementary bodies were incubated with dilutions of CHG gel for various
      times from 0 to 120 min. An aliquot of each dilution was further diluted and was
      inoculated onto McCoy cell monolayers in individual wells in a 96-well microtiter
      plate. The cultures were incubated for 48 h, and the chlamydial inclusions were
      stained and counted. CHG gel diluted fourfold (0.0625% CHG) killed C. trachomatis
      serovar D, and CHG gel diluted eightfold (0.0313% CHG) killed serovar F
      immediately upon exposure. CHG gel diluted 16-fold (0.0156% CHG) killed serovar
      D, and CHG gel diluted 32-fold (0.0078% CHG) killed serovar F after 120 min of
      exposure. Alteration of the pH over the range of from 4 to 8 did not
      significantly affect its activity. The addition of 10% whole human blood
      decreased the CHG gel activity at 0 min but had no significant effect after 120
      min of exposure. We conclude that CHG gel may be effective topically against C.
      trachomatis at concentrations that can be used and under conditions that are
      found in the female genital tract and that further studies of its antimicrobial
      efficacy and toxicity in vivo are warranted.

PMID- 9661013
TI  - Comparisons between antimicrobial pharmacodynamic indices and bacterial killing
      as described by using the Zhi model.
AB  - Various suggestions have been made for empirical pharmacodynamic indices of
      antibiotic effectiveness, such as areas under the drug concentration-time curve
      in serum (AUC), AUC > MIC, AUC/MIC, area under the inhibitory curve (AUIC), AUC
      above MIC, and time above MIC (T > MIC). In addition, bacterial growth and
      killing models, such as the Zhi model, have been developed. The goal of the
      present study was to compare the empirical behavior of the Zhi model of bacterial
      growth and killing with the other empirical pharmacodynamic indices described
      above by using simulated clinical data analyzed with the USC*PACK PC clinical
      programs for adaptive control of drug therapy, with one model describing a
      concentration-dependent antibiotic (tobramycin) and another describing a
      concentration-independent antibiotic (ticarcillin). The computed relative number
      of CFU was plotted against each pharmacodynamic index, with each axis
      parameterized over time. We assumed that a good pharmacodynamic index should
      present a clear and continuous relationship between the time course of its values
      and the time course of the bacterial killing as seen with the Zhi model.
      Preliminary work showed that some pharmacodynamic indices were very similar. A
      good sensitivity to the change in the values of the MIC was shown for AUC/MIC and
      also for T > MIC. In addition, the time courses of some other pharmacodynamic
      indices were very similar. Since AUC/MIC is easily calculated and shows more
      sensitivity, it appeared to be the best of the indices mentioned above for the
      concentration-dependent drug, because it incorporated and used the MIC the best.
      T > MIC appeared to be the best index for a concentration-independent drug. We
      also propose a new composite index, weighted AUC (WAUC), which appears to be
      useful for both concentration-dependent and concentration-independent drugs.

PMID- 9661014
TI  - P-glycoprotein-mediated transport of itraconazole across the blood-brain barrier.
AB  - The mechanism for the accumulation of itraconazole (ITZ) in its elimination from
      the brain was studied in rats and mice. The concentration of ITZ in liver tissue
      declined in parallel with the plasma ITZ concentration until 24 h after
      intravenous injection of the drug (half-life, 5 h); however, the ITZ in brain
      tissue rapidly disappeared (half-life, 0.4 h). The time profiles of the
      brain/plasma ITZ concentration ratio (Kp value) showed a marked overshooting, and
      the Kp value increased with increasing dose; these phenomena were not observed in
      the liver tissue. This finding indicates the occurrence of a nonlinear efflux of
      ITZ from the brain to the blood. Moreover, based on a pharmacokinetic model which
      hypothesized processes for both nonlinear and linear effluxes of ITZ from the
      brain to the blood, we found that the efflux rate constant in the saturable
      process was approximately sevenfold larger than that in the nonsaturable process.
      The Kp value for the brain tissue was significantly increased in the presence of
      ketoconazole or verapamil. The brain Kp value for mdr1a knockout mice was also
      significantly increased compared with that of control mice. Moreover, the uptake
      of vincristine or vinblastine, both of which are substrates of the P glycoprotein
      (P-gp), into mouse brain capillary endothelial cells was also significantly
      increased by ITZ or verapamil. In conclusion, P-gp in the brain capillary
      endothelial cells participates in a process of active efflux of ITZ from the
      brain to the blood at the blood-brain barrier, and ITZ can be an inhibitor of
      various substrates of P-gp.

PMID- 9661015
TI  - Entry of sanfetrinem into human polymorphonuclear granulocytes and its cell
      associated activity against intracellular, penicillin-resistant Streptococcus
      pneumoniae.
AB  - The entry of antibiotics into phagocytes is necessary for activity against
      intracellular pathogens. The ability of sanfetrinem, the first member of a new
      class of antibiotics, to penetrate human polymorphonuclear granulocytes and its
      consequences upon subsequent phagocytosis and killing of ingested penicillin
      resistant Streptococcus pneumoniae have been evaluated. Sanfetrinem penetrated
      into human polymorphonuclear leukocytes (PMNs) at all concentrations tested, with
      cellular concentration/extracellular concentration ratios of 6.6 to 5.03 and 4.21
      when sanfetrinem was used at 0.25 to 0.5 and 1 microgram/ml, respectively, within
      30 min of incubation. The uptake was complete within 5 min and was not energy
      dependent, since it was not affected by cell viability, environmental
      temperature, or the addition of a metabolic inhibitor. At a concentration of one
      half the MIC, sanfetrinem significantly enhanced human PMN phagocytosis and
      increased intracellular bactericidal activity against penicillin-resistant S.
      pneumoniae. Following preexposure of PMNs to a concentration of one-half the MIC
      of sanfetrinem, there was a significant increase in both phagocytosis and killing
      compared with that for the controls, indicating the ability of sanfetrinem to
      interact with biological membranes and remain active within PMNs. Preexposure of
      streptococci to sanfetrinem made penicillin-resistant S. pneumoniae more
      susceptible to the bactericidal mechanisms of human PMNs than untreated
      organisms.

PMID- 9661016
TI  - Effects of DU-6859a, a new quinolone antimicrobial, on theophylline metabolism in
      in vitro and in vivo studies.
AB  - In vitro and in vivo studies were conducted to investigate the drug interaction
      between a new quinolone antimicrobial, DU-6859a, and theophylline (TP). The
      effect of DU-6859a on TP metabolism was evaluated in vitro by measuring the rate
      of TP metabolite formation by using human liver microsomes. DU-6859a inhibited
      the metabolism of TP, especially the formation of 1-methylxanthine, in vitro, but
      to a lesser extent than other drugs that are known to interact with TP. TP was
      administered alone (200 mg twice a day [b.i.d.] for 9 days) or in combination
      with DU-6859a (50 or 100 mg b.i.d. for 5 days) to six healthy subjects. DU-6859a
      administered at a dose of 50 mg resulted in no changes in serum TP
      concentrations, and slight increases in serum TP concentrations were observed at
      a dose of 100 mg. Moreover, the administration of 100 mg of DU-6859a resulted in
      decreases in all urinary TP metabolites, with significant differences. It appears
      that although DU-6859a has a weak inhibitory effect on TP metabolism in vitro,
      its concomitant use with TP at clinical dosage levels does not cause any adverse
      effects, showing only a slight increase in blood TP concentrations and a decrease
      in urinary metabolites.

PMID- 9661017
TI  - NADPH cytochrome P-450 oxidoreductase and susceptibility to ketoconazole.
AB  - The phenotype of a strain of Saccharomyces cerevisiae containing a disruption of
      the gene encoding NADPH cytochrome P-450 oxidoreductase (CPR) was quantified
      biochemically and microbiologically, as were those of various transformants of
      this strain after expression of native CPR, cytochrome P-45051 (CYP51), and a
      fusion protein of CYP51-CPR (FUS). Only a 4-fold decrease in ergosterol
      biosynthesis was observed for the cpr strain, but ketoconazole sensitivity
      increased 200-fold, indicating hypersensitivity to the alternative electron donor
      system in cpr strains. Both phenotypes could be reversed in transformants
      expressing the CPR and FUS, indicating the availability of the CPR in FUS as well
      as the expressed native CPR for monoxygenase-associated reactions. The
      complementation of function was observed both in vitro and in vivo for the
      monoxygenases squalene epoxidase, CYP51, and CYP61 in the ergosterol biosynthesis
      pathway with which CPR is coupled. Overexpression of CYP51 and FUS produced
      different levels of ketoconazole resistance in wild-type cells, indicating that
      the availability of CPR may limit the potential of overproduction of CYP51 as a
      mechanism of resistance to azole antifungal agents.

PMID- 9661018
TI  - Bacterial pathogens isolated from patients with bloodstream infection:
      frequencies of occurrence and antimicrobial susceptibility patterns from the
      SENTRY antimicrobial surveillance program (United States and Canada, 1997).
AB  - The SENTRY Program was established in January 1997 to measure the predominant
      pathogens and antimicrobial resistance patterns of nosocomial and community
      acquired infections over a broad network of sentinel hospitals in the United
      States (30 sites), Canada (8 sites), South America (10 sites), and Europe (24
      sites). During the first 6-month study period (January to June 1997), a total of
      5,058 bloodstream infections (BSI) were reported by North American SENTRY
      participants (4,119 from the United States and 939 from Canada). In both the
      United States and Canada, Staphylococcus aureus and Escherichia coli were the
      most common BSI isolates, followed by coagulase-negative staphylococci and
      enterococci. Klebsiella spp., Enterobacter spp., Pseudomonas aeruginosa,
      Streptococcus pneumoniae, and beta-hemolytic streptococci were also among the 10
      most frequently reported species in both the United States and Canada. Although
      the rank orders of pathogens in the United States and Canada were similar,
      distinct differences were noted in the antimicrobial susceptibilities of several
      pathogens. Overall, U.S. isolates were considerably more resistant than those
      from Canada. The differences in the proportions of oxacillin-resistant S. aureus
      isolates (26.2 versus 2.7% for U.S. and Canadian isolates, respectively),
      vancomycin-resistant enterococcal isolates (17.7 versus 0% for U.S. and Canadian
      isolates, respectively), and ceftazidime-resistant Enterobacter sp. isolates
      (30.6 versus 6.2% for U.S. and Canadian isolates, respectively) dramatically
      emphasize the relative lack of specific antimicrobial resistance genes (mecA,
      vanA, and vanB) in the Canadian microbial population. Among U.S. isolates,
      resistance to oxacillin among staphylococci, to vancomycin among enterococci, to
      penicillin among pneumococci, and to ceftazidime among Enterobacter spp. was
      observed in both nosocomial and community-acquired pathogens, although in almost
      every instance the proportion of resistant strains was higher among nosocomial
      isolates. Antimicrobial resistance continues to increase, and ongoing
      surveillance of microbial pathogens and resistance profiles is essential on
      national and international scales.

PMID- 9661019
TI  - Antiproliferative effects and mechanism of action of SCH 56592 against
      Trypanosoma (Schizotrypanum) cruzi: in vitro and in vivo studies.
AB  - We have investigated the antiproliferative effects of SCH 56592, a new
      experimental triazole, against Trypanosoma (Schizotrypanum) cruzi, the
      etiological agent of Chagas' disease in Latin America. SCH 56592 blocked the
      proliferation of the epimastigote form of the parasite in vitro at 30 nM, a
      concentration 30- to 100-fold lower than that required with the reference
      compounds ketoconazole and itraconazole. At that concentration all the parasite's
      endogenous sterols (ergosterol, 24-ethyl-cholesta-5,7,22-trien-3 beta-ol, and its
      22-dihydro analogs), were replaced by methylated sterols (lanosterol and 24
      methylene-dihydrolanosterol), as revealed by high-resolution gas chromatography
      coupled with mass spectrometry. This indicated that the primary mechanism of
      action of the drug was inhibition of the parasite's sterol C-14 alpha
      demethylase. Against the clinically relevant intracellular amastigote form, grown
      in cultured Vero cells at 37 degrees C, the MIC of SCH 56592 was 0.3 nM, again 33
      to 100-fold lower than that of ketoconazole or itraconazole. In a murine model
      of acute Chagas' disease, SCH 56592 given at > or = 10 mg/kg of body weight/day
      for a total of 43 doses allowed 85 to 100% survival and 90 to 100% cure of the
      surviving animals, as verified by parasitological, serological, and PCR-based
      tests, while ketoconazole given at 30 mg/kg day allowed 60% survival but only 20%
      cure. In a murine model of chronic Chagas' disease, SCH 56592 was again more
      effective than ketoconazole, providing 75 to 85% protection from death, with 60
      to 75% parasitological cures of the surviving animals, while no parasitological
      cures were observed with ketoconazole. The results indicate that SCH 56592 is the
      most powerful sterol biosynthesis inhibitor ever tested against T. cruzi and may
      be useful in the treatment of human Chagas' disease.

PMID- 9661020
TI  - NorM, a putative multidrug efflux protein, of Vibrio parahaemolyticus and its
      homolog in Escherichia coli.
AB  - We found that cells of Vibrio parahaemolyticus possess an energy-dependent efflux
      system for norfloxacin. We cloned a gene for a putative norfloxacin efflux
      protein from the chromosomal DNA of V. parahaemolyticus by using an Escherichia
      coli mutant lacking the major multidrug efflux system AcrAB as the host and
      sequenced the gene (norM). Cells of E. coli transformed with a plasmid carrying
      the norM gene showed elevated energy-dependent efflux of norfloxacin. The
      transformants showed elevated resistance not only to norfloxacin and
      ciprofloxacin but also to the structurally unrelated compounds ethidium,
      kanamycin, and streptomycin. These results suggest that this is a multidrug
      efflux system. The hydropathy pattern of the deduced amino acid sequence of NorM
      suggested the presence of 12 transmembrane domains. The deduced primary structure
      of NorM showed 57% identity and 88% similarity with that of a hypothetical E.
      coli membrane protein, YdhE. No reported drug efflux protein in the sequence
      databases showed significant sequence similarity with NorM. Thus, NorM seems to
      be a novel type of multidrug efflux protein. We cloned the ydhE gene from E.
      coli. Cells of E. coli transformed with the cloned ydhE gene showed elevated
      resistance to norfloxacin, ciprofloxacin, acriflavine, and tetraphenylphosphonium
      ion, but not to ethidium, when MICs were measured. Thus, it seems that NorM and
      YdhE differ somehow in substrate specificity.

PMID- 9661021
TI  - Population pharmacokinetics of ceftizoxime administered by continuous infusion in
      clinically ill adult patients.
AB  - Ceftizoxime is a widely used beta-lactam antimicrobial agent, but pharmacokinetic
      data for use with clinically ill patients are lacking. We studied the population
      pharmacokinetics of ceftizoxime in 72 clinically ill patients at a community
      based, university-affiliated hospital. A population pharmacokinetic model for
      ceftizoxime was created by using a prospective observational design. Ceftizoxime
      was administered by continuous infusion to treat patients with proven or
      suspected bacterial infections. While the patients were receiving infusions of
      ceftizoxime, serum samples were collected for pharmacokinetic analysis with the
      nonlinear mixed-effect modeling program NONMEM. In addition to clearance and
      volume of distribution, various comorbidities were examined for their influence
      on the kinetics. All 72 subjects completed the study, and 114 serum samples were
      collected. Several demographic and comorbidity variables, namely, age, weight,
      serum creatinine levels, congestive heart failure, and long-term ventilator
      dependency, had a significant impact on the estimate for ceftizoxime clearance. A
      mixture model, or two populations for estimation of ceftizoxime clearance, was
      discovered. One population presented with an additive clearance component of 1.6
      liters per h. In addition, a maximizer function for serum creatinine levels was
      found. In summary, two models for ceftizoxime clearance, mixture and nonmixture,
      were found and are presented. Clearance for ceftizoxime can be estimated with
      commonly available clinical information and the models presented. From the
      clearance estimates, the dose of ceftizoxime to maintain the desired
      concentration in serum can be determined. Work is needed to validate the model
      for drug clearance and to evaluate its predictive performance.

PMID- 9661022
TI  - Multidose pharmacokinetics of ritonavir and zidovudine in human immunodeficiency
      virus-infected patients.
AB  - The effect of coadministration of ritonavir and zidovudine (ZDV) on the
      pharmacokinetics of these drugs was investigated in a three-period, multidose,
      crossover study. Eighteen asymptomatic, human immunodeficiency virus-positive men
      were assigned randomly to six different sequences of the following three
      regimens: ZDV (200 mg every 8 h [q8h] alone for 4 days, ritonavir (300 mg q6h)
      alone for 4 days, and ZDV with ritonavir for 4 days. Ritonavir pharmacokinetics
      were unaffected by coadministration with ZDV. However, ZDV exposure was reduced
      by about 26% (P < 0.05) in the presence of ritonavir. The maximum concentration
      in (Cmax) of ZDV plasma decreased from 748 +/- 375 (mean +/- standard deviation)
      to 546 +/- 296, and area under the concentration-time curve from 0 to 24 h (AUC0
      24) decreased from 3,052 +/- 1,007 to 2,261 +/- 715 when coadministered with
      ritonavir. In contrast, the ZDV elimination rate constant was unaffected by
      ritonavir, suggesting that there was no change in ZDV systemic metabolism.
      Correspondingly, differences in ZDV-glucuronide Cmax and AUC were not
      statistically significantly different between regimens (P > 0.31). Also, there
      were no apparent differences in the formation of 3'-amino-3'-deoxythymidine or in
      the adverse event profiles between the regimens. The lack of change in ritonavir
      pharmacokinetics suggests that dosage adjustment of ritonavir is unnecessary when
      it is administered concurrently with ZDV. The clinical relevance of a 26%
      reduction in ZDV exposure when ZDV is administered with ritonavir is unknown. In
      addition to other multidrug regimens, the long-term safety and efficacy of
      coadministration of ritonavir and ZDV is being investigated.

PMID- 9661023
TI  - Characterization of a staphylococcal plasmid related to pUB110 and carrying two
      novel genes, vatC and vgbB, encoding resistance to streptogramins A and B and
      similar antibiotics.
AB  - We isolated and sequenced a plasmid, named pIP1714 (4,978 bp), which specifies
      resistance to streptogramins A and B and the mixture of these compounds. pIP1714
      was isolated from a Staphylococcus cohnii subsp. cohnii strain found in the
      environment of a hospital where pristinamycin was extensively used. Resistance to
      both compounds and related antibiotics is encoded by two novel, probably
      cotranscribed genes, (i) vatC, encoding a 212-amino-acid (aa) acetyltransferase
      that inactivates streptogramin A and that exhibits 58.2 to 69.8% aa identity with
      the Vat, VatB, and SatA proteins, and (ii) vgbB, encoding a 295-aa lactonase that
      inactivates streptogramin B and that shows 67% aa identity with the Vgb
      lactonase. pIP1714 includes a 2,985-bp fragment also found in two rolling-circle
      replication and mobilizable plasmids, pUB110 and pBC16, from gram-positive
      bacteria. In all three plasmids, the common fragment was delimited by two direct
      repeats of four nucleotides (GGGC) and included (i) putative genes closely
      related to repB, which encodes a replication protein, and to pre(mob), which
      encodes a protein required for conjugative mobilization and site-specific
      recombination, and (ii) sequences very similar to the double- and single-strand
      origins (dso, ssoU) and the recombination site, RSA. The antibiotic resistance
      genes repB and pre(mob) carried by each of these plasmids were found in the same
      transcriptional orientation.

PMID- 9661024
TI  - Metabolism of 2',3'-dideoxy-2',3'-didehydro-beta-L(-)-5-fluorocytidine and its
      activity in combination with clinically approved anti-human immunodeficiency
      virus beta-D(+) nucleoside analogs in vitro.
AB  - 2',3'-Dideoxy-2',3'-didehydro-beta-L(-)-5-fluorocytidine [L(-)Fd4C] has been
      reported to be a potent inhibitor of the human immunodeficiency virus (HIV) in
      cell culture. In the present study the antiviral activity of this compound in two
      drug combinations and its intracellular metabolism are addressed. The two-drug
      combination of L(-)Fd4C plus 2',3'-didehydro-2'-3'-dideoxythymidine (D4T, or
      stavudine) or 3'-azido-3'-deoxythymidine (AZT, or zidovudine) synergistically
      inhibited replication of HIV in vitro. Additive antiviral activity was observed
      with L(-)Fd4C in combination with 2',3'-dideoxycytidine (ddC, or zalcitabine) or
      2',3'-dideoxyinosine (ddI, or didanosine). This beta-L(-) nucleoside analog has
      no activity against mitochondrial DNA synthesis at concentrations up to 10
      microM. As we previously reported for other beta-L(-) nucleoside analogs, L(
      )Fd4C could protect against mitochondrial toxicity associated with D4T, ddC, and
      ddI. Metabolism studies showed that this drug is converted intracellularly to its
      mono-, di-, and triphosphate metabolites. The enzyme responsible for
      monophosphate formation was identified as cytoplasmic deoxycytidine kinase, and
      the K(m) is 100 microM. L(-)Fd4C was not recognized in vitro by human
      mitochondrial deoxypyrimidine nucleoside kinase. Also, L(-)Fd4C was not a
      substrate for deoxycytidine deaminase. L(-)Fd4C 5'-triphosphate served as an
      alternative substrate to dCTP for incorporation into DNA by HIV reverse
      transcriptase. The favorable anti-HIV activity and protection from mitochondrial
      toxicity by L(-)Fd4C in two-drug combinations favors the further development of
      L(-)Fd4C as an anti-HIV agent.

PMID- 9661025
TI  - Anti-hepatitis B virus activity and metabolism of 2',3'-dideoxy-2',3'-didehydro
      beta-L(-)-5-fluorocytidine.
AB  - 2',3'-Dideoxy-2',3'-didehydro-beta-L(-)-5-fluorocytidine [L(-)Fd4C] was found to
      be at least 10 times more potent than beta-L-2',3'-dideoxy-3'-thiacytidine [L(
      )SddC; also called 3TC, or lamivudine]against hepatitis B virus (HBV) in culture.
      Its cytotoxicity against HepG2 growth in culture was also greater than that of L(
      )SddC (3TC). There was no activity of this compound against mitochondrial DNA
      synthesis in cells at concentrations upto 10 microM. The dynamics of recovery of
      virus from the medium of cells pretreated with equal drug concentrations were
      slower with L(-)Fd4C than with L(-)SddC (3TC). L(-)Fd4C could be metabolized to
      mono-, di-, and triphosphate forms. The degree of L(-)Fd4C phosphorylation to the
      5'-triphosphate metabolite was higher than the degree of L(-)SddC (3TC)
      phosphorylation when equal extracellular concentrations of the two drugs were
      used. The apparent K(m) of L(-)Fd4C phosphorylated metabolites formed
      intracellularly was higher than that for L(-)SddC (3TC). This may be due in part
      to a difference in the behavior of L(-)Fd4C and L(-)SddC (3TC) towards cytosolic
      deoxycytidine kinase. Furthermore, L(-)Fd4C 5'-triphosphate was retained longer
      within cells than L(-)SddC (3TC) 5-triphosphate. L(-)Fd4C 5'-triphosphate
      inhibited HBV DNA polymerase in competition with dCTP with a Ki of 0.069 +/-
      0.015 microM. Given the antiviral potency and unique pharmacodynamic properties
      of L(-)Fd4C, this compound should be considered for development as an expanded
      spectrum anti-HBV drug.

PMID- 9661026
TI  - Molecular basis of in vivo resistance to sulfadoxine-pyrimethamine in African
      adult patients infected with Plasmodium falciparum malaria parasites.
AB  - In vitro sulfadoxine and pyrimethamine resistance has been associated with point
      mutations in the dihydropteroate synthase and dihydrofolate reductase domains,
      respectively, but the in vivo relevance of these point mutations has not been
      well established. To analyze the correlation between genotype and phenotype, 10
      Cameroonian adult patients were treated with sulfadoxine-pyrimethamine and
      followed up for 28 days. After losses to follow-up (n = 1) or elimination of DNA
      samples due to mixed parasite populations with pyrimethamine-sensitive and
      pyrimethamine-resistant profiles (n = 3), parasite genomic DNA from day 0 blood
      samples of six patients were analyzed by DNA sequencing. Three patients who were
      cured had isolates characterized by a wild-type or mutant dihydrofolate reductase
      gene (with one or two mutations) and wild-type dihydropteroate synthase gene.
      Three other patients who failed to respond to sulfadoxine-pyrimethamine treatment
      carried isolates with triple dihydrofolate reductase gene mutations and either a
      wild-type or a mutant dihydropteroate synthase gene. Three dihydrofolate
      reductase gene codons (51, 59, and 108) may be reliable genetic markers that can
      accurately predict the clinical outcome of sulfadoxine-pyrimethamine treatment in
      Africa.

PMID- 9661027
TI  - Pharmacokinetics of the protease inhibitor KNI-272 in plasma and cerebrospinal
      fluid in nonhuman primates after intravenous dosing and in human immunodeficiency
      virus-infected children after intravenous and oral dosing.
AB  - KNI-272 is a human immunodeficiency virus (HIV) protease inhibitor with potent
      activity in vitro. We studied the pharmacokinetics of KNI-272 in the plasma and
      cerebrospinal fluid (CSF) of a nonhuman primate model and after intravenous and
      oral administration to children with HIV infection. Plasma and CSF were sampled
      over 24 h after the administration of an intravenous dose of 50 mg of KNI-272 per
      kg of body weight (approximately 1,000 mg/m2) to three nonhuman primates. The
      pharmacokinetics of KNI-272 were also studied in 18 children (9 males and 9
      females; median age, 9.4 years) enrolled in a phase I trial of four dose levels
      of KNI-272 (100, 200, 330, and 500 mg/m2 per dose given four times daily). The
      plasma concentration-time profile of KNI-272 in the nonhuman primate model was
      characterized by considerable interanimal variability and rapid elimination
      (clearance, 2.5 liters/h/kg; terminal half-life, 0.54 h). The level of drug
      exposure achieved in CSF, as measured by the area under the KNI-272 concentration
      time curve, was only 1% of that achieved in plasma. The pharmacokinetics of KNI
      272 in children were characterized by rapid elimination (clearance, 276
      ml/min/m2; terminal half-life, 0.44 h), limited (12%) and apparently saturable
      bioavailability, and limited distribution (volume of distribution at steady
      state, 0.11 liter/kg). The concentrations in plasma were maintained above a
      concentration that is active in vitro for less than half of the 6-h dosing
      interval. There was no significant increase in CD4 cell counts or decrease in p24
      antigen or HIV RNA levels. The pharmacokinetic profile of KNI-272 may limit the
      drug's efficacy in vivo. It appears that KNI-272 will play a limited role in the
      treatment of HIV-infected children.

PMID- 9661028
TI  - Identification and expression of multidrug transporters responsible for
      fluconazole resistance in Candida dubliniensis.
AB  - Candida dubliniensis is a recently described Candida species associated with oral
      candidosis in human immunodeficiency virus (HIV)-infected and AIDS patients, from
      whom fluconazole-resistant clinical isolates have been previously recovered.
      Furthermore, derivatives exhibiting a stable fluconazole-resistant phenotype have
      been readily generated in vitro from fluconazole-susceptible isolates following
      exposure to the drug. In this study, fluconazole-resistant isolates accumulated
      up to 80% less [3H] fluconazole than susceptible isolates and also exhibited
      reduced susceptibility to the metabolic inhibitors 4-nitroquinoline-N-oxide and
      methotrexate. These findings suggested that C. dubliniensis may encode multidrug
      transporters similar to those encoded by the C. albicans MDR1, CDR1, and CDR2
      genes (CaMDR1, CaCDR1, and CaCDR2, respectively). A C. dubliniensis homolog of
      CaMDR1, termed CdMDR1, was cloned; its nucleotide sequence was found to be 92%
      identical to the corresponding CaMDR1 sequence, while the predicted CdMDR1
      protein was found to be 96% identical to the corresponding CaMDR1 protein. By
      PCR, C. dubliniensis was also found to encode homologs of CDR1 and CDR2, termed
      CdCDR1 and CdCDR2, respectively. Expression of CdMDR1 in a fluconazole
      susceptible delta pdr5 null mutant of Saccharomyces cerevisiae conferred a
      fluconazole-resistant phenotype and resulted in a 75% decrease in accumulation of
      [3H]fluconazole. Northern analysis of fluconazole-susceptible and -resistant
      isolates of C. dubliniensis revealed that fluconazole resistance was associated
      with increased expression of CdMDR1 mRNA. In contrast, most studies showed that
      overexpression of CaCDR1 was associated with fluconazole resistance in C.
      albicans. Increased levels of the CdMdr1p protein were also detected in
      fluconazole-resistant isolates. Similar results were obtained with fluconazole
      resistant derivatives of C. dubliniensis generated in vitro, some of which also
      exhibited increased levels of CdCDR1 mRNA and CdCdr1p protein. These results
      demonstrate that C. dubliniensis encodes multidrug transporters which mediate
      fluconazole resistance in clinical isolates and which can be rapidly mobilized,
      at least in vitro, on exposure to fluconazole.

PMID- 9661029
TI  - Determination of the excitatory potencies of fluoroquinolones in the central
      nervous system by an in vitro model.
AB  - Fluoroquinolones have been reported to induce central nervous system side
      effects, including seizures and psychiatric events. Although relatively rare in
      patients up to now, the proconvulsant activity depends on the chemical structure
      and might be a critical endpoint of some new representatives of this valuable
      class of antimicrobials. The electrophysiological determination of field
      potentials in the CA1 region of the rat hippocampus slice allowed an assessment
      of the excitatory potential of fluoroquinolones and might be predictive for their
      neurotoxic potency in vivo. An optimization of this method and its extension to
      other fluoroquinolones resulted in a defined rank order. Well-known already
      marketed quinolones as well as some fluoroquinolones under evaluation and
      development were used. The dose range tested was between 0.5 and 4 mumol/liter,
      which was comparable to the therapeutic concentration in the brain. All tested
      compounds increased the population spike amplitude in a concentration-dependent
      manner, and the resulting excitatory potency was highly dependent on the chemical
      structure, with compounds ranging from least to most excitatory as follows:
      ofloxacin, ciprofloxacin, nalidixic acid, moxifloxacin, BAY x 8843, [corrected]
      fleroxacin, lomefloxacin, enoxacin, clinafloxacin (much more excitatory than
      enoxacin), tosufloxacin, trovafloxacin, BAY 15-7828, and BAY x 9181 (much more
      excitatory than BAY 15-7828). The proposed hippocampus slice model not only is
      suitable for giving valuable alerts as to convulsive potential during candidate
      selection but also enables mechanistic investigations. These investigations
      pointed to the N-methyl-D-aspartate receptor as the probable target of the
      fluoroquinolone effects.

PMID- 9661030
TI  - Efficacy of trovafloxacin, a new quinolone antibiotic, in experimental
      staphylococcal endocarditis due to oxacillin-resistant strains.
AB  - Therapeutic options for severe infections caused by strains of oxacillin
      resistant Staphylococcus aureus (ORSA) and coagulase-negative staphylococci
      (ORSE) are very limited. With the increasing resistance of such strains to
      aminoglycosides, rifampin, and currently available quinolone agents, as well as
      the recent documentation of increasing resistance of ORSA to vancomycin (VANCO),
      new treatment alternatives are imperative. The in vivo efficacy of trovafloxacin
      (TROVA), a new quinolone agent with excellent antistaphylococcal activity in
      vitro, against experimental endocarditis (IE) due to beta-lactamase-producing
      ORSA and ORSE strains (ORSA and ORSE IE) was evaluated. TROVA (25 mg/kg of body
      weight intravenously [i.v.] twice daily [b.i.d]) was compared to VANCO (20 mg/kg
      i.v. b.i.d.) and two regimens of ampicillin-sulbactam (AMP-SUL; 200 mg/kg
      intramuscularly [i.m.] three times a day [t.i.d.] and 20 mg/kg i.m. b.i.d.), with
      all agents given for 3 or 6 days. AMP-SUL was included as a comparative treatment
      regimen because of its proven efficacy against experimental ORSA and ORSE IE. For
      both ORSA and ORSE IE, TROVA, AMP-SUL, and VANCO each reduced staphylococcal
      densities in vegetations compared to untreated controls (P < 0.01). For ORSA IE,
      TROVA was the most rapidly bactericidal agent--although not to a statistically
      significant degree--correlating with its superior bactericidal effect in vitro
      compared to those of VANCO and AMP-SUL.

PMID- 9661031
TI  - Dosing of aminoglycosides to rapidly attain pharmacodynamic goals and hasten
      therapeutic response by using individualized pharmacokinetic monitoring of
      patients with pneumonia caused by gram-negative organisms.
AB  - Achieving a peak aminoglycoside concentration (Cmax)/MIC of > or = 10 within 48 h
      of initiation of therapy for pneumonia caused by gram-negative organisms results
      in a 90% probability of therapeutic response by day 7. Targeting an MIC of 1
      microgram/ml, empirical aminoglycoside loading doses of 348 (25th- to 75th
      percentile range, 275 to 432) mg were calculated to obtain a Cmax/MIC of 10 in
      our patient population. Individualized pharmacokinetic monitoring coupled with
      MIC data should determine subsequent dosing regimens to minimize the potential
      for toxicity and maximize the probability of clinical response.

PMID- 9661032
TI  - Detection of point mutations in rpoB gene of rifampin-resistant Rickettsia typhi.
AB  - The rpoB gene of rifampin-resistant Rickettsia typhi (Rif mutant) and wild-type
      R. typhi were sequenced and compared. The Rif mutant rpoB had three nucleotide
      substitutions, which resulted in amino acid changes at residues 151, 201, and 271
      and may be the basis for the rifampin resistance.

PMID- 9661033
TI  - Antimicrobial susceptibility testing of 59 strains of Campylobacter fetus subsp.
      fetus.
AB  - The susceptibilities of 59 Campylobacter fetus subsp. fetus isolates to eight
      antibiotics were studied by the agar dilution, E-test, and disk diffusion
      methods. None of the isolates were beta-lactamase producers. All were susceptible
      to ampicillin, gentamicin, imipenem, and meropenem as determined by the three
      methods, with MICs at which 90% of the isolates are inhibited (MIC90s)
      (determined by agar dilution) of 2, 1, < or = 0.06, and 0.12 microgram/ml,
      respectively. Twenty-seven percent of the isolates were resistant to
      tetracycline, with complete agreement between the agar dilution and disk
      diffusion results. The MIC90s determined by agar dilution were 2 micrograms/ml
      for erythromycin, 1 microgram/ml for ciprofloxacin, and 8 micrograms/ml for
      cefotaxime.

PMID- 9661034
TI  - Energy-dependent accumulation of fluoroquinolones in quinolone-resistant
      Klebsiella pneumoniae strains.
AB  - The intracellular accumulation of norfloxacin and pefloxacin in Klebsiella
      pneumoniae was evaluated. The roles of lipopolysaccharide, capsule, and outer
      membrane proteins were not important for the intrabacterial accumulation of
      fluoroquinolones in isogenic strains with known outer membrane alterations. In
      fluoroquinolone-resistant clinical isolates also expressing GyrA alterations, an
      active efflux leading to decreased accumulation of the drugs enhanced their
      resistance to these agents.

PMID- 9661035
TI  - Contribution of rpoB mutations to development of rifamycin cross-resistance in
      Mycobacterium tuberculosis.
AB  - The contributions of 23 insertion, deletion, or missense mutations within an 81
      bp fragment of rpoB, the gene encoding the beta-subunit of the DNA-dependent RNA
      polymerase of Mycobacterium tuberculosis, to the development of resistance to
      rifamycins (rifampin, rifabutin, rifapentine, and KRM-1648) in 29 rifampin
      resistant clinical isolates were defined. Specific mutant rpoB alleles led to the
      development of cross-resistance to all rifamycins tested, while a subset of
      mutations were associated with resistance to rifampin and rifapentine but not to
      KRM-1648 or rifabutin. To further study the impact of specific rpoB mutant
      alleles on the development of rifamycin resistance, mutations were incorporated
      into the rpoB gene of M. tuberculosis H37Rv, contained on a mycobacterial shuttle
      plasmid, by in vitro mutagenesis. Recombinant M. tuberculosis clones containing
      plasmids with specific mutations in either codon 531 or 526 of rpoB exhibited
      high-level resistance to all rifamycins tested, whereas clones containing a
      plasmid with a mutation in codon 516 exhibited high-level resistance to rifampin
      and rifapentine but were susceptible to both rifabutin and KRM-1648. These
      results provided additional proof of the association of specific rpoB mutations
      with the development of rifamycin resistance and corroborate previous reports of
      the usefulness of rpoB genotyping for predicting rifamycin-resistant phenotypes.

PMID- 9661036
TI  - In vivo antibacterial activities of sanfetrinem cilexetil, a new oral tricyclic
      antibiotic.
AB  - The in vivo antibacterial activities of a new oral trinem, sanfetrinem cilexetil
      (a prodrug of sanfetrinem), were evaluated in comparison with those of cefdinir
      and amoxicillin. Sanfetrinem cilexetil showed potent efficacy against
      experimental murine septicemia caused by Staphylococcus aureus, Streptococcus
      pyogenes, and Escherichia coli and against murine respiratory infections caused
      by Streptococcus pneumoniae. Likewise, in murine models of respiratory infection
      by penicillin-susceptible and penicillin-resistant S. pneumoniae, sanfetrinem
      cilexetil was more effective than amoxicillin in reducing the number of bacteria
      in infected lungs. These results were reflected in its potent in vitro activity
      and high levels in plasma.

PMID- 9661037
TI  - Enhanced bioavailability of itraconazole in hydroxypropyl-beta-cyclodextrin
      solution versus capsules in healthy volunteers.
AB  - The bioavailabilities and bioequivalences of single 200-mg doses of itraconazole
      solution and two capsule formulations were evaluated in a crossover study of 30
      male volunteers. The two capsule formulations were bioequivalent. The
      bioavailabilities of the solutions itraconazole and hydroxyitraconazole were 30
      to 33% and 35 to 37% greater, respectively, than those of either capsule.
      However, the maximum concentrations of the drug in plasma (Cmax), the times to
      Cmax, and the terminal half-lives were comparable for all three formulations.
      These data indicate that the bioavailabilities of itraconazole and
      hydroxyitraconazole are enhanced when administered as an oral solution instead of
      capsules.

PMID- 9661038
TI  - Inhibitory effect of erythromycin on superoxide anion production by human
      neutrophils primed with granulocyte-colony stimulating factor.

PMID- 9661039
TI  - In vitro susceptibilities of Bordetella pertussis and Bordetella parapertussis to
      BAY 12-8039, trovafloxacin, and ciprofloxacin.

PMID- 9661040
TI  - Bactericidal activities of ceftizoxime and cefotaxime against Streptococcus
      pneumoniae.

PMID- 9661041
TI  - Effect of recombinant growth factors on human saphenous vein smooth muscle cells.

PMID- 9661042
TI  - Evidence of p53-induced apoptosis in cancer cells exposed to taxol.

PMID- 9661043
TI  - Transepithelial potential of cultured branchial epithelia from rainbow trout
      under symmetrical conditions.

PMID- 9661044
TI  - Establishment and characterization of a typical primitive neuroectodermal tumor
      cell line.

PMID- 9661046
TI  - Electrophoretic pattern changes in macrophage cell lines due to culture in
      protein-free medium.

PMID- 9661045
TI  - Long-term culture of murine bone-marrow-derived endothelial cells.

PMID- 9661047
TI  - Desmin expression in mesangial cells and fibroblasts in vitro.

PMID- 9661048
TI  - Receptor expression, cytogenetic, and molecular analysis of six continuous human
      glioma cell lines.
AB  - Six human glioma cell lines were established from tissues obtained from five
      patients diagnosed with Kernohan grade IV glioblastoma multiforme and one from a
      patient with a grade II astrocytoma. One line was from a recurrent patient who
      had received prior therapy; the other lines were derived from patients at initial
      diagnosis and/or before cytoreductive therapies other than surgery were given.
      Considerable variability in phenotypic, karyotypic, and cell surface marker
      expression was displayed between the six human glioma cell lines. The karyotypes
      ranged from apparently normal (grade II astrocytoma) to those with complex
      rearrangements. Trisomy of chromosome 7 was the most common abnormality. The
      extensive cytogenetic and molecular characterization of these lines may
      facilitate their utilization in cellular and molecular biologic studies.

PMID- 9661049
TI  - Establishment of a human fibroblast cell line producing tumor necrosis factor
      alpha (KMST-6/TNF) and growth inhibitory effects of its conditioned medium on
      malignant cells in culture.
AB  - To develop a new gene therapy model for cancer, a clonal cell line (KMST-6/TNF)
      which produces human tumor necrosis factor alpha (hTNF-alpha) has been developed
      by introducing hTNF-alpha cDNA into a human immortal fibroblast cell line (KMST
      6). The conditioned medium (CM) of KMST-6/TNF cells inhibited the growth of
      various malignant human cell lines, but not that of normal human fibroblasts.
      Although the growth inhibitory effects of KMST-6/TNF CM were neutralized to a
      considerable degree by anti-TNF-alpha antibody, its inhibitory effects were more
      marked than the purified human natural TNF-alpha itself in the same units,
      suggesting that KMST-6/TNF CM contains some growth inhibitory substances other
      than TNF-alpha. However, interferons alpha, beta, and gamma were undetectable in
      the KMST-6/TNF CM.

PMID- 9661050
TI  - Isolation of EpH4 mammary epithelial cell subpopulations which differ in their
      morphogenetic properties.
AB  - EpH4 is a nontumorigenic cell line derived from spontaneously immortalized mouse
      mammary gland epithelial cells (Fialka et al., 1996). When grown in collagen
      gels, EpH4 cells give rise to different types of structures, e.g., solid cords or
      branching tubes. By removing and subsequently dissociating single three
      dimensional colonies of defined morphology, we have isolated six clonal
      subpopulations of EpH4 cells which display distinct morphogenetic properties in
      collagen gel cultures. Thus, cells from the H1B clone form branching cords devoid
      of a central lumen, K3A3 cells form cords enclosing small multifocal lumina, and
      J3B1 cells form large cavitary structures containing a wide lumen. I3G2 cells
      form either cords or tubes, depending on the type of serum added to the culture
      medium. Finally, when grown in serum-free medium, Bela cells form spherical
      cysts, whereas Be4a cells form long, extensively branched tubes. In additional
      assays of morphogenesis, i.e., cell sandwiching between two collagen gels or
      culture on a thick layer of Matrigel (a laminin-rich extracellular matrix), all
      clones form epithelial-cell lined cavitary structures, except H1B cells which are
      unable to generate lumina under these conditions. The EpH4 sublines we have
      isolated provide an in vitro system for studying the mechanisms responsible for
      lumen formation and branching morphogenesis, as well as for identifying the
      factors which subvert these developmental processes during mammary
      carcinogenesis.

PMID- 9661051
TI  - An improved method to obtain highly differentiated monolayers of human bronchial
      epithelial cells.
AB  - Electrophysiological studies of human bronchial epithelial cells in vitro are
      limited by the scarcity of biological material available for primary culture. To
      overcome this problem, we set up a protocol in which the cell number is first
      enlarged in LHC9/RPMI 1640 serum-free medium for up to six passages, each passage
      giving a four- to eightfold amplification. The cells are then plated at high
      density on permeable supports. Cell differentiation, monitored by measuring
      transepithelial potential difference (PD) and electrical resistance (R), is
      induced with a medium containing serum and a cocktail of different supplements
      and hormones. Maximal values of PD and R, obtained after 4-7 d of culture on
      permeable supports, are around -50 mV and 3000-4000 omega/cm2, respectively.
      Ussing chamber experiments show that basal short-circuit current (Isc) is
      partially inhibited by the epithelial Na+ channel blocker amiloride. Stimulation
      with a cAMP-elevating agent induces a Isc increase that is inhibited by the
      cystic fibrosis transmembrane conductance regulator (CFTR) blocker glibenclamide.
      Our culture protocol provides a large number of differentiated bronchial
      epithelial cell monolayers starting from a low amount of material. This
      characteristic is useful for in vitro studies of ion transport in airway
      epithelium.

PMID- 9661052
TI  - Three-dimensional culture of hepatocytes in a continuously flowing medium.
AB  - Rat hepatocytes were maintained on three-dimensional cultures on sponge discs
      kept in Spinner Baskets (New Brunswick Scientific Co., New Brunswick, NJ, USA)
      with continuously circulating serum-free hepatocyte growth medium (HGM)
      containing hepatocyte growth factor (HGF) and epidermal growth factor (EGF).
      Hepatocytes were embedded in polyester sponge discs with a collagen gel at the
      concentration of 5 million cells/ml. Atmospheric gas containing 7% CO2 was
      directly bubbled into the medium. Agitation by the impeller created a continuous
      medium-flow through the packed hepatocytes. Comparison between identically
      prepared perfused and stationery cultures showed that hepatocytes in the perfused
      cultures maintain higher levels of DNA synthesis. These results demonstrate the
      value of perfusion systems and also show that hepatocytes can proliferate and
      maintain differentiation in three-dimensional culture environments.

PMID- 9661053
TI  - Monolayer formation and DNA synthesis of the outer epithelial cells from pearl
      oyster mantle in coculture with amebocytes.
AB  - In vitro experiments were conducted to clarify the involvement of the epithelium
      amebocyte interaction in epithelial regeneration of bivalves. The outer epithelia
      of the pallial mantle of the pearl oyster. Pinctada fucata martensii, were
      separated in cell sheets from the inner connective tissue layers by digestion
      with Dispase. Clumps of the separated mantle epithelia were inoculated onto the
      amebocyte layers prepared on the bottom of culture dishes and maintained at 20
      degrees C in 5% CO2:95% air for 1 wk. Balanced salt solution with 0.03% (wt/vol)
      glucose was used as a culture medium. The epithelial cells adhered to the
      amebocyte layers within 24 h, changed their shape from cuboidal to squamous, and
      migrated and formed monolayer sheets within 3 d. Electron microscopy confirmed
      maintenance of epithelial polarity and cell to cell junction in the sheets; 6 d
      after the inoculation, 5-bromo-2'-deoxyuridine was added to the culture at 30
      microns. After labeling for 24 h, the cultures were fixed and stained with anti 5
      bromo-2'-deoxyuridine antibody. Cells with immunoreactive nuclei were clearly
      observed in the epithelial cell sheets, indicating active DNA synthesis in the
      epithelial sheets. Thus, cocultured with amebocytes, the outer epithelial cells
      from pallial mantle tissue formed a monolayer sheet and started DNA synthesis.
      The morphological features of the mantle outer epithelial cells are analogous to
      those described for the in vivo cutaneous wound healing process, suggesting that
      the epithelium-amebocyte interaction is important in the regeneration of
      epithelium in bivalves.

PMID- 9661054
TI  - Anionic glycoconjugates from differentiated and dedifferentiated cultures of
      bovine articular chondrocytes: modulation by TGF-beta.
AB  - Primary, high density bovine articular chondrocyte (BAC) cultures, stimulated
      with transforming growth factor-beta-1, elaborated a high molecular weight
      anionic glycoconjugate, kDa 540, which does not contain glycosaminoglycan chains
      (Chan and Anastassiades, 1996). The effect of exogenously added transforming
      growth factor-beta-1 on the elaboration of the high molecular weight
      glycoconjugate and of proteoglycans was studied during dedifferentiation of the
      chondrocytes, utilizing a serial subculture technique under anchorage-dependent
      conditions, up to four subcultures. The high molecular weight glycoconjugate was
      detected in the media of all growth-factor-stimulated chondrocyte subcultures, as
      well as stimulated primary cultures, but not in unstimulated primary cultures or
      subcultures. By contrast, a large proteoglycan, was only secreted by primary
      cultures and first subcultures, whether treated with transforming growth factor
      beta-1 or untreated. This proteoglycan contained mostly chondroitin sulfate
      chains, whose hydrodynamic size was increased by the addition of transforming
      growth factor-beta-1. Further, the pattern of the proteoglycans appearing in the
      media of subcultures 2-4 was influenced by the addition of transforming growth
      factor-beta-1, so that while these control subcultures elaborated both the large
      and small chondroitin sulfate proteoglycans, the equivalent stimulated
      subcultures elaborated only intermediate sized chondroitin sulfate
      proteoglycan(s). These results suggest that while dedifferentiation of articular
      chondrocytes, achieved by subculturing, strongly modulates the effect of
      exogenously added transforming growth factor-beta-1 on the type of proteoglycan
      elaborated, the process of dedifferentiation does not influence the transforming
      growth-factor-beta-dependent synthesis of the high molecular weight anionic
      glycoconjugate.

PMID- 9661056
TI  - From Chicago to Budapest, a tale of two cities.

PMID- 9661055
TI  - Macrophage cell lines derived from major histocompatibility complex II-negative
      mice.
AB  - Two bone-marrow-derived macrophage cell lines, C2D and C2Dt, were isolated from
      major histocompatibility class II negative knock-out mice. The C2D cell line was
      stabilized by continuous culture in colony-stimulating factor-1 and the C2Dt cell
      line was transformed with SV40 virus large T antigen. These cells exhibited
      phenotypic properties of macrophages including morphology and expression of Mac 1
      and Mac 2 cell surface molecules. These cells also had comparable growth to the
      bone-marrow-derived macrophage cell line B6MP102. These new cell lines were not
      spontaneously cytotoxic and were only capable of modest killing of F5b tumor
      cells when stimulated with LPS and interferon-gamma, but not when stimulated with
      LPS alone or with staphylococcal exotoxin. C2D and C2Dt cells phagocytosed
      labeled Staphylococcus aureus similarly to B6MP102 cells but less well than C2D
      peritoneal macrophages. These cell lines secreted interleukin-6, but not tumor
      necrosis factor or nitric oxide in response to LPS or staphlococcal enterotoxins
      A or B C2D(t) cells were tumorigenic in C2D and C57BL/6J mice but C2D cells were
      not. These data suggest that macrophage cell lines can be established from bone
      marrow cells of major histocompatibility complex II-negative mice.

PMID- 9661057
TI  - Widening the scope of accreditation--issues and challenges in community and
      primary care.
AB  - Accreditation systems first developed to improve the quality of hospital care. As
      health care systems move towards a greater emphasis on primary and home care,
      accreditation systems are developing to address quality in this more diverse
      sector. This is more problematic, since there is little agreement about the
      precise functions to be undertaken in non-hospital care and there is no uniform
      organizational structure. This paper addresses the issues raised in developing
      quality in these very different organizations and examines the progress being
      made.

PMID- 9661058
TI  - Fielding standardized patients in primary care settings: lessons from a study
      using unannounced standardized patients to assess preventive care practices.
AB  - OBJECTIVES: To document detection and suspicion rates of unannounced standardized
      patients visiting community-based practices. DESIGN: Primary care physicians were
      recruited to participate in a study using standardized patients. Four
      standardized patient scenarios were used. SETTING: Community-based primary care
      physicians' practices in southern Ontario between September 1994 and August 1995.
      STUDY PARTICIPANTS: Sixty-two primary care physicians. MAIN OUTCOME MEASURES: A
      'believability' questionnaire completed after all four standardized patients had
      visited the practices. RESULTS: Of the primary care physicians approached, 50%
      (62) agreed to participate. Twenty-one per cent of all visits were suspected as
      standardized patient encounters. Forty-six per cent suspected one or more
      standardized patients. Only five physicians (8%) suspected all four standardized
      patients. Reasons for suspecting standardized patients were associated with the
      characteristics of the physician's practices, the physician's practice profile
      and the standardized patient cover story. CONCLUSION: The portrayal of
      asymptomatic patients seeking a new primary care physician presents unique
      challenges. Carefully constructed cover stories, and detailed knowledge of the
      local area and of the practices of the participating physicians is required to
      allow standardized patients cases to be tailored to fit into primary care
      settings without arousing suspicion.

PMID- 9661059
TI  - Measuring change in health in general practice: a comparison of a simple
      transition question with the Nottingham Health Profile.
AB  - OBJECTIVE: To compare a simple transition question with a standard measure of
      distress [the Nottingham Health Profile (NHP)] in the measurement of change in
      health of patients attending general practitioners. SETTINGS AND SUBJECTS: Two
      hundred and thirty one patients attending for acute or chronic illness, or follow
      up consultations in a single general practice. MEASURES: Patients completed the
      NHP at the consultation and again after 2 weeks. They also completed the
      transition question after 2 weeks, which asked how the patient felt in comparison
      with 2 weeks before. In addition, patients in the chronic category were reviewed
      at 2 weeks by the general practitioner. Analysis sought the level of agreement
      between the changes in NHP scores and the transition question responses. RESULTS:
      Levels of correlation between changes in NHP scores and the transition question
      were low, and for patients with chronic illness correlation was only moderate
      between the transition question and the general practitioner's assessment. The
      transition question was less sensitive to deterioration in health. CONCLUSIONS:
      Caution is required in the interpretation of finding from the use of simple
      transition questions that ask patients how they feel. Further evaluation of
      transition questions with different wording and format is required.

PMID- 9661060
TI  - Does the care given by general practitioners and midwives to patients with
      (imminent) miscarriage meet the wishes and expectations of the patients?
AB  - OBJECTIVE: In 1989 a Dutch national guideline on (imminent) miscarriage was
      developed for use in general practice. A prospective recording study was carried
      out to determine how the patients evaluated the care they received from general
      practitioners (GPs) and midwives who agreed to adhere to this (imminent)
      miscarriage guideline and to determine the aspects that influence this
      evaluation. SETTING: GP practices and midwifery practices in The Netherlands.
      DESIGN: Prospective recording of appointments during 4 consecutive weeks in a
      diary by patients who contacted their GP or midwife with symptoms of (imminent)
      miscarriage. STUDY PARTICIPANTS: Over a period of 12 months, 75 GPs and 43
      midwives recorded all patients (n = 407) showing symptoms of (imminent)
      miscarriage. In total 265 patients had completed at least the first contact in
      the diary; 200 patients actually recorded all contacts. RESULTS: Most patients
      gave their GP or midwife a high evaluation score (8.2 or 8.7 respectively). Yet,
      20% thought that the care could be improved if the GP or midwife gave more
      information, was more empathetic and carried out an ultrasound scan. In
      determining the aspects that have most influence on the patients' evaluation,
      empathy and support came first, followed by involvement of the patient in
      decision making, putting her at ease, and the total duration of the contacts.
      Although patients who wanted a referral gave a lower score, this seems to be of
      less importance than the above mentioned aspects. Expecting and getting an
      ultrasound scan did not influence the patient's evaluation.

PMID- 9661061
TI  - How well are patients treated in family practice? Quality of consultations for
      non-acute abdominal complaints.
AB  - OBJECTIVE: To describe the application of weighted review criteria, developed by
      the Delphi technique, for the assessment of the quality of consultations
      concerning non-acute, abdominal complaints. DESIGN: Descriptive study in two
      parts: (i) comparison of actual family doctor (FD)-performance with predefined
      review criteria; (ii) calculation of quality scores per consultation, utilizing
      the weighted criteria. SETTINGS: Sixty-two family practices across The
      Netherlands. SUBJECT: Eight-hundred and forty consultations concerning non-acute
      abdominal complaints, first encounters. MAIN OUTCOME MEASURES: The percentage of
      consultations in which each criterion was met; quality scores per consultation
      and their distribution. RESULTS: (i) Little effort was made to trace risk groups
      for gastrointestinal malignancies (< 50% of the consultations concerned);
      medication was often described without dietary advice (17%); inappropriate
      activities were not carried out on a large scale (6%). (ii) Quality scores were
      normally distributed. CONCLUSIONS: The Delphi technique yields a useful
      instrument for assessment of the quality of consultations. The review criteria
      for quality assessment of FD performance used in this study made it possible to
      distinguish quite clearly between high- and low-quality consultations. Some
      important deficiencies in daily practice emerged.

PMID- 9661062
TI  - Quality differences between rural and urban primary care: the case of a cervical
      cancer screening programme.
AB  - OBJECTIVE: To measure the difference between rural and urban primary care quality
      in terms of an early cervical cancer detection programme. LOCATIONS: Seven
      hundred and fifty smear reports from rural primary care units and 750 from urban
      primary care units were selected at random from three institutions: the Ministry
      of Health, the largest Mexican social security institution, and one University
      Hospital, during August 1995-March 1996. Excluded were reports from women who
      were pregnant, menopausal or those who had undergone hysterectomy, as well as
      those tested positive for dysplasia and cancer. ACTIVITIES: Quality was measured
      through indicators and standards set by consensus of recognized field experts,
      based mainly on recommended national and international parameters. RESULTS: There
      was no difference between the overall quality of the urban and rural units. Both
      registered fairly satisfactory levels (achievement: 76.2%; 95% CI: 72.7-77.0%,
      versus 75.2; 95% CI: 69.8-78.9%, respectively). The quality of the smear sampling
      was highly unsatisfactory in rural units and unsatisfactory in urban units
      (achievement: 64.2%; 95% CI: 58.2-70.0%, versus 47.3%, 95% CI: 42-52.7%; P <
      0.00001). Quality of coverage was unsatisfactory for both regions. Quality of
      smear processing and timeliness were highly satisfactory for both rural and urban
      units. RECOMMENDATIONS: Efforts should be directed toward smear quality
      improvement, especially in rural units. Health care workers who take smears need
      training programmes and better instruments. They should receive feedback on smear
      adequacy from the laboratory. Health education is necessary to improve
      utilization and programme coverage quality.

PMID- 9661063
TI  - Evaluation of turnaround times as a component of quality assurance in surgical
      pathology.
AB  - OBJECTIVE: As a part of a quality assurance program in anatomic pathology, a
      study was conducted to determine intralaboratory components of turnaround time
      according to specimen type, and to compare the present data with results obtained
      2 years after implementing the program. DESIGN: Assessment of intralaboratory
      turnaround times for surgical pathology reports in a sample of 501 biopsies and
      surgical specimens during 1992. Comparison between the basal data obtained in
      1992 and the final determination in 1994 after the implementation of an
      improvement action. SETTING: Surgical specimens and biopsies accessioned at the
      Department of Anatomic Pathology of a 913-bed acute-care teaching hospital in the
      city of Barcelona, Spain. STUDY SAMPLES AND PARTICIPANTS: The sample was selected
      from the total number of biopsies and surgical specimens accessioned on specific
      days by applying a table of random numbers. Data were collected from the request
      forms, final report copies, and laboratory registries of turnaround time-points
      by two resident physicians. INTERVENTIONS: All relevant information concerning
      turnaround times was recorded following a standardized questionnaire developed
      specifically for the study. MAIN OUTCOME MEASURES: The basal determination for
      turnaround time for pathologic diagnosis in 1992 was 5.7 days. RESULTS: The mean
      turnaround time for the 501 specimens was 6.24 (SD = 3.16; range = 2-27 days).
      Turnaround times varied substantially according to specimen type. Endoscopic
      biopsy samples were completed by 5.19 days (SD = 2.18). Bone biopsies were
      finalized within a mean of 8.11 days of receipt (SD = 3.18). For the diagnosis of
      lymphoproliferative disorders, most lymph node specimens required special
      histochemical or immunohistochemical stains. The mean turnaround time for results
      reporting/results transmittal to the ordering physician varied between 1.14 and
      1.66 days. The 1992 annual mean turnaround time for a total of 14,862 surgical
      pathology specimens was 5.7 days as compared with 4.2 days for a total of 17,931
      surgical pathology specimens in 1994.

PMID- 9661064
TI  - Eliciting expert opinion using the Delphi technique: identifying performance
      indicators for cardiovascular disease.
AB  - Combining opinion from expert panels is becoming a more common method of
      selecting criteria to define quality of health care. The Rand Corporation
      pioneered this method is the 1950s and 1960s in the context of forecasting
      technological events. Since then, numerous organizations have adopted the
      methodology to develop local and national policy. In the context of quality of
      care, opinion is typically elicited from a sample of experts regarding the
      appropriateness or importance of a medical treatment for several well-defined
      clinical cohorts. The information from the experts is then combined in order to
      create a standard or performance measure of care. This article describes how to
      use the panel process to elicit information from diverse panels of experts.
      Methods are demonstrated using the data from five distinct panels convened as
      part of the Harvard Q-SPAN-CD study, a nationally-funded project whose goal is to
      identify a set of cardiovascular-related performance measures.

PMID- 9661065
TI  - Introducing quality assurance to health service delivery--some approaches from
      South Africa, Ghana and Kenya.
AB  - The following report combines the contributions of four health care professionals
      engaged in quality improvement activities in three different areas of Africa-
      Ghana in West Africa, Kenya in the East, and the Republic of South Africa. These
      reports provide current and vivid accounts of the impact of quality assurance and
      quality improvement activities on areas of change in each country's rapidly
      expanding health care system.

PMID- 9661066
TI  - International Standards and Accreditation for Health Care. Feasibility paper.

PMID- 9661067
TI  - ISQua Accreditation Symposium, Chicago 1997.

PMID- 9661068
TI  - 1998 National Conference on Quality in Health, Kuala Lumpur, Malaysia.

PMID- 9661069
TI  - Paget's disease of bone.
AB  - Paget's disease of bone is a localized disorder of bone remodeling. Increased
      numbers of larger than normal osteoclasts initiate the process at affected
      skeletal sites, and the increase in bone resorption is followed by an increase in
      new bone formation, altering bone architecture. The signs and symptoms of Paget's
      disease are varied, depending in part on the location of the involved sites and
      the degree of increased bone turnover. Recent progress in Paget's disease
      research includes new data regarding the etiology of this disorder and the
      ongoing development of more effective therapies. Although the cause of Paget's
      disease remains unproven, the creation of pagetic osteoclasts seems ever more
      likely to result from both genetic and environmental factors. Many studies
      indicate that in patients with Paget's disease, both osteoclasts and their
      precursors harbor evidence of a paramyxovirus infection, although not all studies
      confirm this finding. Very recent genetic investigations have identified one
      candidate gene on chromosome 18q, although genetic heterogeneity is almost
      certainly present. Advances in treatment have resulted from the availability of
      several potent bisphosphonate compounds (e.g., pamidronate, alendronate, and
      risedronate) that, unlike earlier treatments, produce normal or near normal bone
      turnover indices in a majority of patients. New bone formation after such
      treatment has a more normal, lamellar pattern, and mineralization abnormalities
      are rare to absent with the newer compounds. The availability of such agents has
      prompted a more aggressive management philosophy in which both symptomatic
      disease and also asymptomatic disease at sites with a risk of progression and
      future complications are viewed as clear indications for pharmacologic
      intervention.

PMID- 9661070
TI  - Regulation of prostaglandin G/H synthase-2 expression by interleukin-1 in human
      osteoblast-like cells.
AB  - Interleukin-1 (IL-1) is an important factor in bone metabolism, and its actions
      may be mediated in part via prostaglandins. Prostaglandin G/H synthase (PGHS), a
      critical enzyme in the synthesis of prostaglandins, has two isoforms, PGHS-1,
      which is generally constitutively expressed, and PGHS-2, which is inducible. This
      study examines the effects of IL-1 on PGHS-2 mRNA expression in human
      osteosarcoma MG-63 cells, the human osteoblast-like initial transfectant (HOBIT)
      cell line, and primary human osteoblastic (HOB) cells. IL-1 induced PGHS-2 mRNA
      expression in MG-63 cells within 1 h, and expression was maintained for 24 h.
      There was a dose-related increase in PGHS-2 mRNA levels with 1-100 ng/ml of IL-1.
      Induction of PGHS-2 protein and media prostaglandin E2 (PGE2) paralleled
      induction of PGHS-2 mRNA levels. IL-1 similarly induced PGHS-2 mRNA expression
      and PGE2 production in HOBIT and HOB cells. Among other potential agonists,
      phorbol myristate acetate (PMA) was a potent inducer of PGHS-2 expression, while
      forskolin (FSK), serum, and prostaglandins had little effect. Cycloheximide
      enhanced effects of both IL-1 and PMA, suggesting that de novo protein synthesis
      is not required for induction of PGHS-2. Twenty-four hours of PMA pretreatment
      blocked the induction of PGHS-2 by PMA but not by IL-1, suggesting that IL-1
      induction of PGHS-2 mRNA is not dependent on the protein kinase C pathway.
      Although FSK alone had little effect, it enhanced induction of PGHS-2 mRNA by IL
      1. PGHS-1 was constitutively expressed and showed little change with treatment.
      In summary, we show that IL-1 is a potent inducer of PGHS-2 expression and PGE2
      production in human osteosarcoma cells as well as in osteoblastic cells derived
      from normal human bone.

PMID- 9661071
TI  - Interleukin-1 represses COLIA1 promoter activity in calvarial bones of transgenic
      ColCAT mice in vitro and in vivo.
AB  - Interleukin-1 (IL-1) inhibits collagen synthesis in osteoblastic cell lines and
      primary osteoblast-like cells. However, promoter elements regulating type I
      collagen A1 (COLIA1) expression in vivo and in organ culture may differ from
      those regulating expression in cell culture. We have examined the effects of IL-1
      on reporter gene activity in neonatal transgenic mouse calvariae bearing COLIA1
      promoter-chloramphenicol acetyltransferase (ColCAT) fusion genes. The parent
      construct, ColCAT 3.6, contains 3.5 kb of 5' flanking sequence and 115 bp of 5'
      untranslated region fused to the CAT reporter. In 48-h calvarial organ cultures,
      IL-1 repressed ColCAT 3.6 promoter activity and collagen synthesis in a dose
      related manner, with a maximal inhibition of 40-65%. This repression was retained
      in 5' deletion constructs truncated to-1719 bp. The inhibition of transgene mRNA
      was blocked by cycloheximide, indicating a requirement for new protein synthesis.
      Pretreatment with indomethacin diminished the inhibitory effect of IL-1 on CAT
      activity and collagen synthesis, suggesting partial mediation by prostaglandins.
      Local in vivo injection of IL-1 (500 ng) decreased calvarial transgene mRNA after
      8 h, an effect that was partially blocked by indomethacin. ColCAT transgenic mice
      represent a useful model for in vitro and in vivo assessment of COLIA promoter
      regulation by cytokines and other factors.

PMID- 9661072
TI  - Increased interleukin-6 production in mouse osteoblastic MC3T3-E1 cells
      expressing activating mutant of the stimulatory G protein.
AB  - The McCune-Albright syndrome (MAS) is characterized by polyostotic fibrous
      dysplasia, cafe-au-lait spots, and multiple endocrine hyperfunction. An
      activating missense mutation of the alpha subunit of the Gs protein (Gs alpha)
      was found in several affected tissues, resulting in prolonged stimulation of
      adenylate cyclase. Our recent study has indicated that the cells derived from the
      fibrous bone dysplasia tissues in MAS patients produced increased levels of
      interleukin-6 (IL-6), which may be responsible for the increased bone resorption
      in this disease. In the present investigation, to analyze the molecular mechanism
      of the increased IL-6 production by activating mutant Gs alpha in bone cells, we
      established mouse osteoblastic MC3T3-E1 cells stably transfected with the
      activating mutant Gs alpha expression vector. These cells showed a significant
      increase of intracellular cAMP levels and produced a higher amount of IL-6 than
      the cells transfected with control vector or wild-type Gs alpha expression
      vector. Analysis of the IL-6 promoter revealed that any of the AP-1, nuclear
      factor (NF)-IL-6, and NF-kappa B binding elements are important for the
      activating mutant Gs alpha-induced gene expression. Electrophoretic mobility
      shift assays using nuclear extracts of the mutant Gs alpha-expressing cells
      showed that phospho(Ser133)-cAMP-responsive element binding protein (CREB), AP-1,
      NF-IL6, and NF-kappa B were increased, compared with the control cells or the
      wild-type Gs alpha-expressing cells. These results indicate that activating
      mutant Gs alpha increases the transcriptional factors binding to CRE, AP-1, NF
      IL6, and NF-kappa B elements to induce IL-6 gene expression in the osteoblastic
      cells.

PMID- 9661073
TI  - Regulation of interleukin-6 production by prostaglandin E2 in fetal rat
      osteoblasts: role of protein kinase A signaling pathway.
AB  - Prostaglandin E2 (PGE2) is an abundant eicosanoid in bone that has been
      implicated in a number of pathological states associated with bone loss.
      Interleukin-6 (IL-6) is a cytokine that plays a critical role in bone remodeling
      and appears to act as a downstream effector of most bone-resorbing agents. In
      light of the evidence that PGE2 induces IL-6 in the bone environment, this study
      was designed to investigate whether PGE2 regulated IL-6 expression by
      osteoblasts. Here we demonstrate that PGE2 is a potent inducer of IL-6 production
      by fetal rat osteoblasts and synergizes with lipopolysaccharide to enhance IL-6.
      We show that PGE2 stimulates the activity of the IL-6 promoter in osteoblasts,
      suggesting that PGE2 controls IL-6 gene expression at least at the
      transcriptional level. Moreover, we show that PGE2-mediated IL-6 induction is
      prevented by the cAMP antagonist, Rp-cAMP, and the protein kinase A (PKA)
      inhibitors, KT5720 and H89. Thus, our data indicate that PGE2 involves the cAMP
      PKA signaling pathway to regulate IL-6 gene expression in osteoblasts.

PMID- 9661074
TI  - Mice lacking osteopontin show normal development and bone structure but display
      altered osteoclast formation in vitro.
AB  - We have used homologous recombination in embryonic stem cells to generate mice
      with a targeted disruption of the osteopontin (Opn, or Spp1, for secreted
      phosphoprotein 1) gene. Mice homozygous for this disruption fail to express
      osteopontin (OPN) as assessed at both the mRNA and protein level, although an N
      terminal fragment of OPN is detectable at extremely low levels in the bones of -/
      animals. The Opn -/- mice are fertile, their litter size is normal, and they
      develop normally. The bones and teeth of animals not expressing OPN are
      morphologically normal at the level of light and electron microscopy, and the
      skeletal structure of young animals is normal as assessed by radiography.
      Ultrastructurally, proteinaceous structures normally rich in OPN, such as cement
      lines, persist in the bones of the Opn-/- animals. Osteoclastogenesis was
      assessed in vitro in cocultures with a feeder layer of calvarial osteoblast cells
      from wild-type mice. Spleen cells from Opn-/- mice cells formed osteoclasts 3- to
      13-fold more frequently than did control Opn+/+ cells, while the extent of
      osteoclast development from Opn -/- bone marrow cells was about 2- to 4-fold more
      than from the corresponding wild-type cells. Osteoclast development occurred when
      Opn-/- spleen cells were differentiated in the presence of Opn-/-osteoblasts,
      indicating that endogenous OPN is not required for this process. These results
      suggest that OPN is not essential for normal mouse development and osteogenesis,
      but can modulate osteoclast differentiation.

PMID- 9661075
TI  - Generation of mouse osteoclastogenic cell lines immortalized with SV40 large T
      antigen.
AB  - Progress in the field of osteoclast gene regulation has been hampered
      significantly by the lack of such cell lines. In this study, mouse osteoclast
      precursor cells were elicited in an osteoclast-inductive coculture system and
      immortalized using SV40 large T antigen. One of the osteoclast precursor cell
      lines (MOCP-5) forms 95% tartrate-resistant acid phosphatase positive (TRAP+)
      multinuclear osteoclast-like cells (OCLs) in the coculture system. The yield of
      TRAP+ OCLs was 4.5-7x10(4) cells per 10 cm2 dish. Expression of SV40 large T
      antigen was visualized in the nucleus of MOCP-5 cells and OCLs by
      immunohistochemistry. MOCP-5 cells were positive for MoMa-2 antigen and
      nonspecific esterase but negative for F4/80 antigen. OCLs derived from MOCP-5
      cells were positive for able to form extensive resorption bone pits on bone
      slices. The resorbing activity of the OCLs was comparable to that of authentic
      mouse osteoclasts. Pit formation was inhibited by salmon calcitonin (CT). Acid
      production by OCLs was demonstrated by vital staining with acridine orange. The
      OCLs expressed cathepsin K and CT receptors. MOCP-5 cells could be transfected by
      a construct that carries the beta-galactosidase gene. Transfected MOCP-5 cells
      expressing beta-galactosidase retain the ability to differentiate into OCLs,
      indicating a useful model for osteoclast gene regulation. To date, the MOCP-5
      cell line has been maintained in continuous culture for 23 months and has
      maintained the capacity to differentiate into osteoclasts throughout this time.
      In summary, these data show that a stable immortalized osteoclast precursor cell
      line has been established and that the immortalization with SV40 large T oncogene
      does not prevent osteoclast precursor cell differentiation.

PMID- 9661076
TI  - Response of biochemical markers of bone turnover to hormone replacement therapy:
      impact of biological variability.
AB  - Biochemical markers of bone turnover may be useful to monitor patients taking
      hormone replacement therapy (HRT). The aim of this study was to assess the
      utility of markers in monitoring HRT by comparing the response of a large panel
      of markers to HRT with their within subject variability. We measured the response
      of markers to transdermal estradiol in 11 postmenopausal women over 24 weeks. We
      measured the within subject variability of markers in 11 untreated healthy
      postmenopausal women over the same period. The mean decrease in markers of bone
      formation after 24 weeks treatment ranged from 19% for procollagen type I C
      terminal propeptide (PICP) to 40% for procollagen type I N-terminal propeptide
      (PINP). The mean decrease in markers of bone resorption ranged from 10% for
      tartrate-resistant acid phosphatase (TRAP) to 67% for C-terminal cross-linked
      telopeptide The least significant change (LSC at p < 0.05), calculated from the
      within subject variability in the untreated group, was used to define response.
      LSC for osteocalcin was 21%, bone alkaline phosphatase 28%, PICP 24%, PINP 21%,
      type I collagen telopeptide 28%, TRAP 17%, urinary calcium 90%, hydroxyproline
      75%, total deoxypyridinoline 47%, free pyridinoline 36%, free deoxypyridinoline
      26%, N-terminal cross-linked telopeptide 70%, and C-terminal cross-linked
      telopeptide 132%. The greatest number of responders after 24 weeks of treatment
      were found using PINP and osteocalcin (9 each), and free deoxypyridinoline (8
      each) and total deoxypyridinoline (8 each) and total deoxypyridinoline (7 each).
      Lumbar spine bone mineral density defined four patients as responders. The
      ability to detect a response differs between markers and is not dependent on the
      magnitude of response to therapy.

PMID- 9661077
TI  - Bone mineral density and its change in pre-and perimenopausal white women: the
      Michigan Bone Health Study.
AB  - There is a need to better understand potential bone mineral density (BMD) loss
      during the menopausal transition since this period may include the initiation of
      interventions. The study purpose was to determine if there was BMD loss at the
      femoral neck, lumbar spine, or total body bone sites in a population-based study
      of women approaching or transitioning the midlife. The 583 enrollees were 25-45
      years of age at the first of four annual measurements from 1992 through 1996.
      Bone mineral content and bone width were measured using dual-energy X-ray
      absorptiometry. Considering all enrollees collectively, there was a significant 3
      year decline (1%) in BMD at the femoral neck over the 3-year period (p = 0.076).
      There was no significant annual change in the lumbar spine (p = 0.11), and a
      significant annual increase in the total body BMD (p = 0.0003). Within subgroups
      and cross-sectionally, BMD values of the femoral neck were 5% lower in women
      classified as perimenopausal compared with premenopausal enrollees; BMD was 3%
      and 1% lower at the lumbar spine and total body site, respectively.
      Longitudinally, among perimenopausal women, a double oophorectomy was associated
      with BMD loss in the spine (p = 0.0003), even though 75-85% of these women had a
      hormone replacement prescription at some time during the study period. In
      summary, the site with evidence of loss was the femoral neck, specifically among
      perimenopausal women. There was little evidence of substantial total body or
      lumbar spine BMD loss in premenopausal women with ovaries who maintained follicle
      stimulating hormone levels < 20 mIU/l in the early follicular period. Double
      oophorectomy, even with hormone replacement, was associated with bone loss.

PMID- 9661078
TI  - Type of physical activity, muscle strength, and pubertal stage as determinants of
      bone mineral density and bone area in adolescent boys.
AB  - The present study was conducted to evaluate the influence of different types of
      weight-bearing physical activity, muscle strength, and puberty on bone mineral
      density (BMD, g/cm2) and bone area in adolescent boys. Three different groups
      were investigated. The first group consisted of 12 adolescent badminton players
      (age 17.0 +/- 0.8 years) training for 5.2 +/- 1.9 h/week. The second group
      consisted of 28 ice hockey players (age 16.9 +/- 0.3 years) training for 8.5 +/-
      2.2 h/week. The third group consisted of 24 controls (age 16.8 +/- 0.3 years)
      training for 1.4 +/- 1.4h/week. The groups were matched for age, height, and
      pubertal stage. BMD, bone mineral content (BMC, g), and the bone area of the
      total body, lumbar spine, hip, femur and tibia diaphyses, distal femur, proximal
      tibia, and humerus were measured using dual-energy X-absorptiometry. When
      adjusting for the difference in body weight between the groups, the badminton
      players were found to have significantly higher BMD (p < 0.05) of the trochanter
      and distal femur compared with the ice hockey players despite a significantly
      lower weekly average training. The badminton players had higher BMD compared with
      the control with the control group at all weight-bearing BMD sites, except at the
      diaphyses of the femur and tibia and lumbar spine. The independent predictors of
      bone density were estimated by adjusting BMC for the bone area in a multivariate
      analysis among all subjects (n = 64). Accordingly, the bone density of all sites
      except the spine was significantly related to muscle strength and height, and the
      bone density of the total body, neck, trochanter, distal femur, and proximal
      tibia was significantly related to type of physical activity (beta = 0.09-0.33, p
      < 0.05). The bone area values at different sites were strongly related to muscle
      strength and height and less strongly related to the type of physical activity
      and pubertal stage. In conclusion, it seems that during late puberty in
      adolescent boys the type of weight-bearing physical activity is an important
      determinant of bone density, while the bone area is largely determined by
      parameters related to body size. The higher BMD at weight-bearing sites in
      badminton players compared with ice hockey players, despite significantly less
      average weekly training, indicates that physical activity including jumps in
      unusual directions has a great osteogenic potential.

PMID- 9661079
TI  - The Tromso Study: physical activity and the incidence of fractures in a middle
      aged population.
AB  - We have studied the relation of occupational and recreational physical activity
      to fractures at different locations. All men born between 1925 and 1959 and all
      women born between 1930 and 1959 in the city of Tromso were invited to
      participate in surveys in 1979-1980 and 1986-1987 (The Tromso Study). Of 16,676
      invited persons, 12,270 (73.6%) attended both surveys. All nonvertebral fractures
      (n = 1435) sustained from 1988 to 1995 were registered in the only hospital in
      the area. Average age in the middle of the follow-up period (December 31, 1991)
      was 47.3 years among men and 4501 years among women, ranging from 32 to 66 years.
      Fracture incidence increased with age at all locations among women, but it
      decreased with or was independent of age among men. Low-energetic fractures
      constituted 74.4% of all fractures among women and 55.2% among men. When
      stratifying by fracture location, the most physically active persons among those
      45 years or older suffered fewer fractures in the weight-bearing skeleton
      (relative risk [RR] 0.6, confidence interval [CI] 0.4-0.9, age-adjusted), but not
      in the non-weight-bearing skeleton (RR 1.0, CI 0.7-1.2, age-adjusted) compared
      with sedentary persons. The relative-risk of a low-energetic fracture in the
      weight-bearing skeleton among the most physically active middle-aged was 0.3 (CI
      0.1-0.7) among men and 0.9 (CI 0.4-1.8) among women compared with the sedentary
      when adjusted for age, body mass index, body height, tobacco smoking, and alcohol
      and milk consumption. It seems that the beneficial effect on the skeleton of
      weight-bearing activity is reflected also in the incidence of fractures at
      different sites.

PMID- 9661080
TI  - Treatment with the oral growth hormone secretagogue MK-677 increases markers of
      bone formation and bone resorption in obese young males.
AB  - The effect of 2 months of treatment with the oral growth hormone (GH)
      secretagogue MK-677 on markers of bone metabolism was determined in healthy obese
      male subjects. This was a randomized, double-blind, parallel, placebo-controlled
      study. Twenty-four healthy obese males, 19-49 years of age, with body mass index
      > 30 kg/m2 were treated with MK-677 (25 mg/day; n = 12) or placebo (n = 12) for 8
      weeks. MK-677 increased markers of bone formation; a 23% increase in the carboxy
      terminal propeptide of type I procollagen levels and a 28% increase in
      procollagen III peptide levels were seen with as little as 2 weeks of MK-677
      treatment (p < 0.01 and p = 0.001 vs. placebo, respectively) while a 15% increase
      in serum levels of osteocalcin was not detected until 8 weeks of treatment (p <
      0.01 vs. placebo). Markers of bone resorption were induced within 2 weeks of
      treatment with MK-677; serum levels of the carboxy-terminal cross-linked
      telopeptide of type I collagen were increased 26% at 8 weeks (p = 0.001 vs.
      placebo), and urine hydroxyproline/creatinine and calcium/creatinine ratios at 8
      weeks were increased by 23% (p < 0.05 vs. placebo) and 46% (p < 0.05 vs placebo),
      respectively, MK-677 increased serum insulin-like growth factor binding protein-5
      (IGFBP-5) by 43-44% after 2-8 weeks of treatment (p < 0.01 vs. placebo). Serum
      IGFBP-4 was increased by 25% after 2 weeks of treatment (p < 0.001 vs. placebo)
      but no significant change from baseline was observed after 8 weeks of treatment.
      Plasma interleukin-6 was not significantly changed by active treatment. In
      conclusion, short-term treatment of healthy obese male volunteers with the GH
      secretagogue MK-677 increases markers of both bone resorption and formation.
      Large increases in serum levels of IGF-1 and IGFBP-5 and a transient increase in
      serum IGFBP-4 were found. Future long-term studies are needed to investigate if
      prolonged treatment with MK-677 increases bone mass.

PMID- 9661081
TI  - Hormonal predictors of bone loss in elderly women: a prospective study. The Study
      of Osteoporotic Fractures Research Group.
AB  - To test the hypotheses that baseline concentrations of sex steroids, sex hormone
      binding globulin (SHBG), and calciotropic hormones predict rates of bone loss in
      elderly women, sera were stored at -190 degrees, and calcaneal bone mineral
      density (BMD) was measured in 9704 community-dwelling white women aged 65 and
      over (1986-1988). Hip BMD was measured 2 years later (1900). Repeat measurements
      of a calcaneal and hip BMD were obtained in 1993-1994, after 5.7 and 3.5 years of
      follow-up, respectively. In 1994, sera were assayed for circulating hormone
      levels in random subcohorts of 231 and 218 women who did not report current use
      of hormone replacement therapy at baseline. Lower levels of endogenous estrogens
      and higher SHBG concentrations were associated with more rapid subsequent bone
      loss from both the calcaneus and hip. After adjusting for age and weight, women
      with high SHBG levels (highest quartile < or = 2.3 micrograms/dI) experienced an
      average of 2.2% (95% confidence interval = 1.6%, 2.9%) calcaneal bone loss per
      year compared with 1.2% (0.7%, 1.2%) among women with low SHBG concentrations
      (lowest quartile < 1.1 micrograms/dI; p < 0.01). This association was independent
      of concentrations of other sex hormones. Women with estradiol levels > or = 10
      pg/ml averaged only 0.1% (-0.7%, 0.5%) annual hip bone loss while women with
      levels below 5 pg/ml averaged 0.8% (0.3, 1.2) hip bone loss per year. Lower 25
      hydroxyvitamin D levels were associated with increased hip but not calcaneal bone
      loss. Levels of parathyroid hormone, 1,25-dihydroxyvitamin D, and Calcium were
      not significantly associated with bone loss from the calcaneus or hip.

PMID- 9661082
TI  - In vivo high resolution MRI of the calcaneus: differences in trabecular structure
      in osteoporosis patients.
AB  - The purpose of this study was to use high resolution (HR) magnetic resonance (MR)
      images of the calcaneus to investigate the trabecular structure of patients with
      and without osteoporotic hip fractures and to compare these techniques with bone
      mineral density (BMD) in differentiating fracture and nonfracture patients. Axial
      and sagittal HR MR images of the calcaneus were obtained in 50 female (23
      postmenopausal patients with osteoporotic hip fractures and 27 postmenopausal
      controls). A three-dimensional gradient-echo sequence was used with a slice
      thickness of 500 micron and in plane resolution of 195 x 195 micron. Texture
      analysis was performed using morphological features, analogous to standard
      histomorphometry and fractal dimension. Additionally, BMd measurements of the hip
      (dual-energy X-ray absorptiometry) were obtained in all patients. Significant
      differences between both patient groups were obtained using morphological
      parameters and fractal dimension as well as hip BMD (p < 0.05). Odds ratios for
      the texture parameters apparent (app.) bone volume/total volume and app.
      trabecular separation were higher than for hip BMD. Receiver operator
      characteristic values of texture measures and hip BMD were comparable. In
      conclusion, trabecular structure measures derived from HR MR images of the
      calcaneus can differentiate between postmenopausal women with and without
      osteoporotic hip fractures.

PMID- 9661083
TI  - A dual-label immunofluorometric assay for human osteocalcin.
AB  - Circulating human osteocalcin (hOC) has been shown to be comprised of two main
      forms: the intact 1-49 form and the proteolytic N-terminal midfragment (N-mid)
      spanning amino acid residues 1-43 or 1-44. We used three monoclonal antibodies
      (MAbs) raised against hOC and bovine osteocalcin in developing a dual-label assay
      for the simultaneous measurement of the proportions of the intact and N-mid forms
      in serum samples. The assay is based on time-resolved fluorescence utilizing
      differently labeled trace MAbs. Biotinylated MAb 2H9 is used as a capture
      antibody for both the intact hOC and the N-mid. Tracer MAb 6F9 labeled with a
      Europium (III)-chelate binds to the intact the N-mid and the intact hOC, whereas
      tracer MAb 3G8 labeled with a Terbium (III)-chelate binds to the intact hOC only.
      The simultaneous binding of the antibodies was tested by comparing full-length
      hOC purified from human bone and hOC shortened from the C terminus by four amino
      acid residues with carboxypeptidase Y. Serum hOC measurements with the dual-label
      assay were in agreement with the corresponding single-label assays (r = 0.96 for
      intact + N-mid assay and r = 0.81 for intact assays, n = 91). The lower
      correlation between the intact assays was attributable to proteolytic
      susceptibility of the intact form due to one additional freezing and thawing
      cycle in carrying out the dual-label assay. As measured with the dual-label
      assay, the levels (mean +/- SD) of serum intact + N-mid OC were 6.2 +/- 2.1 ng/ml
      in the premenopausal group (n = 44), 13.9 +/- 4.9 ng/ml in the postmenopausal
      group without hormone replacement therapy (HRT; n = 13), and 7.5 +/- 3.4 ng/ml in
      the postmenopausal group with HRT (n = 13). The levels of intact hOC in the same
      groups were 4.8 +/- 1.4 ng/ml, 9.8 +/- 2.9 ng/ml, and 5.3 +/- 2.1 ng/ml,
      respectively. Whether the main forms of OC or their relative proportions in serum
      can be used for predicting bone diseases or for monitoring the progression and
      management of diseases awaits further investigations.

PMID- 9661084
TI  - Urinary ovarian and gonadotropin hormone levels in premenopausal women with low
      bone mass.
AB  - We hypothesized that lower ovarian and gonadotropin hormone concentrations would
      be associated with lower levels of peak bone mineral density (BMD) in apparently
      normally menstruating women who did not exercise intensively and did not report
      anorexia or bulimia. This hypothesis was evaluated using a case-with-control
      study design (n = 65) which was nested within a population-based longitudinal
      study of peak bone mass (Michigan Bone Health Study) with annual assessment in
      women aged 25-45 years (n = 582). Cases were 31 premenopausal women with BMD of
      the lumbar spine, femoral neck, and total body less than the 10th percentile of
      the distribution, where controls were 34 premenopausal women with BMD between the
      50th and 75th percentile. BMD was measured by dual-energy X-ray absorptiometry.
      In addition to their annual measurement, these 65 participants collected first
      voided morning urine specimens daily through two consecutive menstrual cycles.
      The urine from alternating days of this collection was analyzed for estrone-3
      glucuronide (E1G), pregnanediol glucuronide (PdG), testosterone, and follicle
      stimulating hormone by radioimmunoassay and these values adjusted for daily
      creatinine excretion levels. Additionally, analyses of daily urine specimens for
      luteinizing hormone (uLH) was undertaken to better characterize the possible uLH
      surge. Cases had significantly lower amounts of E1G (p = 0.009) and PdG (p =
      0.002) than did controls, whether amounts were characterized by a mean value, the
      highest value, or the area under the curve, and after statistically controlling
      for body size. Further, when B-splines were used to fit lines to the E1G and PdG
      data across the menstrual cycle, the 95% confidence intervals (CIs) about the
      line for the controls consistently excluded and excluded and exceeded the 95%
      confidence bands for the cases in the time frame associated with the luteal phase
      in ovulatory cycles. Likewise, 95% CIs for the LH surge in controls exceeded the
      fitted line for cases around the time associates with the LH surge. The cases and
      controls were not different according to dietary intake (energy, protein,
      calcium), family history of osteoporosis, reproductive characteristics (parity,
      age at menarche, age of first pregnancy), follicular phase serum hormone levels,
      calciotropic hormone levels, or by evidence of perimenopause. We conclude that
      these healthy, menstruating women with BMD at the lowest 10th percentile from a
      population-based study had significantly lower urinary sex steroid hormone levels
      during the luteal phase of menstrual cycles as compared with hormone levels in
      premenopausal women with BMD between the 50th and 75th percentile of the same
      population-based study, even after considering the role of body size. These data
      suggest that subclinical decreases in circulating gonadal steroids may impair the
      attainment and/or maintenance of bone mass in otherwise reproductively normal
      women.

PMID- 9661085
TI  - Camurati-Engelmann disease: two case reports describing metadiaphyseal dysplasia
      associated with cerebellar ataxia.
AB  - This clinical report describes two patients presenting with progressive
      diaphyseal dysplasia (Camurati-Engelmann Disease) and cerebellar ataxia. The
      clinical and magnetic resonance imaging findings of the bony and cerebellar
      lesions are presented.

PMID- 9661086
TI  - Pseudohypoparathyroidism type Ia: late presentation with intact mental
      development.

PMID- 9661087
TI  - Certification in ECT.

PMID- 9661088
TI  - The use of flumazenil in the anxious and benzodiazepine-dependent ECT patient.
AB  - Many patients who receive electroconvulsive therapy (ECT) are benzodiazepine
      dependent or are anxious and require benzodiazepine drugs. Because these agents
      may diminish the therapeutic effectiveness of ECT, we explored the dosing,
      safety, and efficacy of pre-ECT flumazenil administration, a benzodiazepine
      competitive antagonist, in patients receiving benzodiazepine medications. We
      report our experience with 35 patients who received both flumazenil and
      benzodiazepine drugs during their ECT course. We compared seizure duration with
      and without flumazenil and compared treatment efficacy to 49 patients who
      received ECT without either of these medications. Flumazenil could be safely
      administered with ECT. A few subjects taking higher chronic benzodiazepine
      dosages experienced breakthrough anxiety or withdrawal symptoms, which were well
      managed by dosing flumazenil immediately before the anesthetic agent and by
      immediate posttreatment benzodiazepine administration. A dose of 0.4-0.5 mg was
      adequate for all but those taking the highest benzodiazepine dosages, where 0.8
      1.0 mg resulted in a clinically more effective reversal. No differences in
      efficacy or seizure duration were found as a function of flumazenil
      administration. Flumazenil offers the promise of safe and effective ECT in
      patients receiving benzodiazepine drugs. Follow-up outcome investigation on a
      random assignment basis will be necessary for definitive assessment of the value
      of flumazenil. In addition, the direct effect of benzodiazepine drugs and the
      flumazenil/benzodiazepine combination on ECT seizures remains to be determined.

PMID- 9661089
TI  - Increased platelet 5-HT2 receptor binding after electroconvulsive therapy in
      depression.
AB  - We investigated the effect of electroconvulsive treatment (ECT) on platelet 14C
      serotonin uptake, 3H-paroxetine binding and 5-HT2 receptors in 12 patients (10
      women and 2 men) unresponsive to pharmacological treatment. The mean numbers of
      ECTs given was 6.1 +/- 1.5. Mean treatment days was 14.6 +/- 3.8. Mean percent
      reduction in MADRS scores was 80.7 +/- 19.7 (p < 0.002). The number of 5-HT2
      receptors increased significantly and uniformly after ECT (p = 0.011). There was
      no correlation between the degree of increase in 5-HT2 receptor densities and the
      reduction in MADRS scores after ECT. There was no difference in mean Bmax for
      platelet 3H-paroxetine binding before and after ECT. Bmax increased in six
      patients and decreased in six patients. The study shows an increase in platelet 5
      HT2-receptor densities in depression after repeated ECT. Recognizing the
      similarities between 5-HT2 receptors in platelets and cerebral cortex, it seems
      reasonable to assume that a similar upregulation of cortical 5-HT2 receptors
      occurs after ECT.

PMID- 9661090
TI  - Motor threshold in transcranial magnetic stimulation: a comparison of a
      neurophysiological method and a visualization of movement method.
AB  - Motor threshold is a means of quantifying stimulus in transcranial magnetic
      stimulation. Two methods are used. One involves neurophysiology techniques and
      the other is visualization of movement. The aim was to compare the percentage of
      total machine output (PTMO) necessary to achieve motor threshold using these
      different methods. Neurophysiological and visualization of movement thresholds
      were determined in six subjects. In all subjects, the two thresholds were
      achieved with a < 10% difference in PTMO. Determination of motor threshold with a
      neurophysiological and a visualization of movement method produced similar
      results.

PMID- 9661091
TI  - Propofol and methohexital as anesthetic agents for electroconvulsive therapy
      (ECT): a comparison of seizure-quality measures and vital signs.
AB  - In a randomized crossover study, the influence of the anesthetics methohexital
      and propofol on EEG seizure parameters, seizure-quality measures, vital signs,
      and oxygen saturation (SpO2) and end-tidal carbon dioxide tension (ETCO2) was
      investigated; 146 treatments of 31 patients were analyzed. Significant
      differences were observed between agents for mean postictal pulse and blood
      pressure values. With methohexital, there was a clear postictal increase of mean
      blood pressure from 126/78 mm Hg to 161/102 mm Hg, whereas there was no increase
      with propofol (p = 0.00), and with methohexital, a postictal increase of the mean
      pulse rate from 81 to 90 beats/min and a slight decrease with propofol (79 to 78
      beats/min). There were no differences in the SpO2 and ETCO2. The mean seizure
      duration for unilateral treatments was significantly longer with methohexital
      (52.7 s) compared with propofol (34.1 s; p = 0.000), but there was no difference
      for the seizure-quality measures: postictal suppression index (propofol 79.7%,
      methohexital 77.4%) and mean integrated amplitude (30.2/31.8) were the same for
      both anesthetic agents. The results show that differences in seizure duration are
      unrelated to seizure-quality measures.

PMID- 9661092
TI  - Cost reduction with maintenance ECT in refractory bipolar disorder.
AB  - A case report of outpatient maintenance electroconvulsive therapy (ECT) is
      presented in a patient with bipolar disorder type I refractory to conventional
      medication treatment but responsive to ECT. A cost comparison is made showing
      substantial savings when outpatient maintenance ECT is used in lieu of inpatient
      hospitalization with ECT. A detailed life chart illustrating multiple medication
      trials that failed to stabilize the patient accompanies the financial summary.
      This case highlights the advantages of outpatient maintenance ECT for bipolar
      depression particularly with regard to safety, efficacy, and significant health
      care cost reduction.

PMID- 9661093
TI  - Reversible ischemic neurologic deficit after ECT.
AB  - We report the case of a 58-year-old woman with depression and hypertension in
      whom aphasia, right-sided hemiparesis, and a possible right visual field defect
      were identified during recovery from right unilateral electroconvulsive therapy
      (ECT). The neurologic deficits resolved over a 3-day period; the patient was
      diagnosed with a reversible ischemic neurologic deficit (RIND). Review of the
      patient literature suggests that such cerebrovascular events in the setting of
      ECT are extremely rare and possibly decreasing in frequency. Reasons for such a
      decrease may include improved screening for predisposing cardiovascular
      conditions and the widespread use of neuromuscular blockade, ventilatory support,
      and cardiovascular monitoring during the procedure. Prompt recognition of
      cerebrovascular events is important to prevent complications such as cerebral
      edema, seizures, and aspiration, as well as to use new treatments for stroke.

PMID- 9661094
TI  - Electroconvulsive therapy in a patient with a cerebellar meningioma.
AB  - We report a 66-year-old woman with a cerebellar meningioma who successfully
      received electroconvulsive therapy (ECT) for mania. No special modifications in
      technique were required. A growing literature supports the relative safety of ECT
      in patients with small, stable brain tumors.

PMID- 9661095
TI  - ECT for organic catatonia due to hereditary cerebellar ataxia.

PMID- 9661096
TI  - Selective serotonin reuptake inhibitor discontinuation with ECT and withdrawal
      symptoms.

PMID- 9661097
TI  - Invited essay: sex biases in the diagnosis of personality disorders.
AB  - One of the more difficult issues in the development of each edition of the
      American Psychiatric Association's Diagnostic and Statistical Manual of Mental
      Disorders (DSM) has been a possible sex bias in the personality disorder
      diagnoses. A substantial amount of discussion and research on this issue has
      occurred since the 1980 publication of the third edition of the DSM. It is now
      apparent that there are a number of different ways in which the differential sex
      prevalence rates for the DSM-IV personality disorders could reflect a sex bias,
      including biased diagnostic constructs, biased thresholds for diagnosis, biased
      population sampling, biased application of diagnostic criteria, biased
      instruments of assessment, and biased diagnostic criteria. It is important to
      understand these different forms of sex bias, as each can occur independently of,
      be confused with, and interact with one another. The purpose of this paper is to
      differentiate among, and to describe the support for, each of these different
      forms of sex bias, with the hope of contributing to their recognition and
      ultimate resolution.

PMID- 9661098
TI  - A psychometric evaluation of the Defense Style Questionnaire in methadone
      patients.
AB  - The self-report Defense Style Questionnaire (DSQ) was designed to assess defenses
      along a developmental continuum. Factor analysis of the original DSQ suggested
      that the scale assessed four factors or types of defenses, whereas a more recent
      factor analysis indicated the DSQ measured three-factors: Immature, Neurotic, and
      Mature. No data, however, regarding the reliability or unique construct validity
      of DSQ dimensions was published. This article reports on factor analyses of two
      DSQ versions in a sample of 215 methadone maintenance patients. Results indicate
      that both DSQ versions are unidimensional, assessing only Immature defenses. The
      lack of published psychometric data raises concerns regarding the true
      reliability of DSQ dimensions reported in previous investigations. Prior
      statements based on DSQ findings may have been incorrect if the DSQ factors were
      unreliable. Findings from this investigation stress the importance of requiring
      and evaluating the psychometric integrity of an instrument before employing it in
      research.

PMID- 9661099
TI  - Diagnostic assignment of criteria: clinicians and DSM-IV.
AB  - The study examined clinician matching of diagnostic criteria to selected DSM-IV
      Axis I and II disorders. A national sample of clinical psychologists and
      psychiatrists assigned symptom criteria, presented in scrambled order by axis, to
      DSM-IV diagnoses with which they believed the criteria belonged, without using
      the DSM. On average, clinicians assigned 69% of Axis I criteria and 75% of Axis
      II criteria to the designated DSM-IV diagnosis. The Axis II data represent
      increased agreement over the 66% found for DSM-III-R. Reasons for the increase
      are discussed, focusing on modifications made in DSM-IV and increased familiarity
      with personality disorders. The significantly higher rate of agreement for Axis
      II over Axis I contrasts with typical reliability data which suggests that Axis I
      disorders are better defined. Specific points of disagreement between clinician
      criteria assignments and the DSM-IV are discussed.

PMID- 9661100
TI  - Short-interval test-retest interrater reliability of the Structured Clinical
      Interview for DSM-III-R personality disorders (SCID-II) in outpatients.
AB  - The short-interval test-retest interrater reliability of the Structured Clinical
      Interview for DSM-III-R personality disorders (SCID-II) was studied in a
      psychotherapy outpatient group whose main complaint was mostly an Axis I anxiety
      disorder. Using a test-retest approach to assess interrater reliability, three
      sources of variance were taken into account (rater variance in the elicitation
      and interpretation of information and patient variance across interviews). Base
      rate requirements were established before calculating reliability coefficients.
      On the whole, interrater agreement on the SCID-II was found to be satisfactory,
      except for the histrionic personality traits. This is the first study that has
      estimated short-interval test-retest interrater reliability of the SCID-II in
      outpatients, and also the first that has studied single SCID-II traits and
      dimensional diagnoses. The results found support the use of the SCID-II as a
      diagnostic instrument for clinical and research purposes.

PMID- 9661101
TI  - Patient-informant concordance on the Structured Clinical Interview for DSM-III-R
      personality disorders (SCID-II).
AB  - In the assessment of personality disorders, patients reports can be questioned
      for several reasons, such as lack of insight, shame, and acute psychiatric state.
      High concordance between patient-based and informant-based diagnoses would be an
      indication of the validity of patient reports (convergent validity). The present
      study examined the concordance between 42 psychotherapy outpatients and their
      informants (intimates) on the Structured Clinical Interview for DSM-III-R
      Personality Disorders (SCID-II). Similar to prior studies, low or only modest
      levels of agreement were found. In comparison with evaluations of the personality
      of the patient by the therapist, patient interviews seemed to be more valid than
      informant interviews. Furthermore, couples with high intensity and intimacy in
      the contact generally showed higher agreement than couples with low intensity and
      intimacy. In conclusion, the data slightly suggest that patient reports are more
      valid than informant reports. However, the lack of a golden standard forces us to
      find more evidence before concluding that patient reports on personality result
      in valid diagnoses.

PMID- 9661102
TI  - Factor structure of psychopathy among methadone maintenance patients.
AB  - The proposed two-factor structure of the Psychopathy Checklist (Revised) was
      assessed by confirmatory factor analyses on a sample of 376 community and prison
      based methadones maintenance patients. Confirmatory factor analyses indicated
      that the two-factor model proposed by previous researchers did not fit well with
      the data from this population. Exploratory analyses extracted five interpretable
      factors, three psychological factors (glibness/manipulative, callousness,
      irresponsibility), and two behavioral factors (criminal behaviors, promiscuity),
      which accounted for 61% of the variance. The data provided support for the
      psychometric reliability of the PCL-R, as indicated by a Chronbach's alpha of
      0.83, weighted kappas for concordance between raters ranging from 0.51 to 1.00,
      and 100% agreement on diagnoses of psychopathy between raters. The data indicate
      that a two-factor structure does not adequately capture the dimensions of
      psychopathy in this population. While the factors do fall into distinct
      psychological and behavioral dimensions, more than two general factors are
      required to describe the dimensions of psychopathy.

PMID- 9661103
TI  - Brief communication: criterion validity of the Personality Diagnostic
      Questionnaire-4+ (PDQ-4+) in a mixed psychiatric sample.
AB  - Three hundred consecutively admitted in- and outpatients were administered the
      Personality Diagnostic Questionnaire-4+ (PDQ-4+). The Structured Clinical
      Interview for DSM-IV Axis II Personality Disorders, Version 2.0 (SCID-II) was
      used as the external diagnostic standard for personality disorder (PD)
      assessment. SCID-II was administered blind to PDQ-4+ scores. Low agreement
      between PDQ-4+ and SCID-II was observed for both dimensional and categorical PD
      evaluations. Receiver operating characteristic (ROC) analysis showed a
      definitively satisfactory discriminatory capability only for two PDQ-4+ PD scales
      (dependent, and antisocial). In agreement with previous studies, these results
      showed that PDQ-4+ was not a substitute for a structured diagnostic interview.

PMID- 9661104
TI  - Brief communication: pathological narcissism in bipolar disorder patients.
AB  - The occurrence of pathological narcissism in bipolar patients, and the diagnostic
      relation between narcissistic personality disorder (NPD) and bipolar disorder
      (BD), were investigated. The Diagnostic Interview for Narcissism (DIN) was
      administered to bipolar patients when manic and when euthymic. The scores were
      compared to those of an NPD sample and a control group of general psychiatric
      patients. Euthymic bipolars do not exhibit a higher level of pathological
      narcissism or a higher prevalence of NPD than psychiatric patients in general.
      However, when manic, bipolar patients do appear similar to the narcissistic
      group, sharing 12 out of 14 of the identifying criteria for NPD. The results
      support the inclusion of mania in the differential diagnosis of NPD.

PMID- 9661105
TI  - Residency training in dental public health: assessment of status, needs, and
      issues.
AB  - The opportunities for public health training have declined over the years while
      the need for public health skills is likely to increase. This paper reports the
      results of a project, sponsored by the Health Resources and Services
      Administration, which answers the question of "how best to invest in the dental
      public health education system so as to fulfill the profession's responsibilities
      to protect and improve the oral health of individuals and society." An
      information base on dental public health education, practice, and specialization
      was developed from an extensive review of the literature and a survey of dentists
      concerning employment and practice requirements for public health dentists. An
      advisory group considered this information, met to discuss the issues involved in
      dental public health training, and provided advice to the project staff. Based on
      the information gathered as part of the project, recommendations were made to:
      (1) develop a grant program to support advanced education in dental public
      health; (2) increase the competencies of dentists who are working in public
      health positions and not eligible for board certification via off-site
      residencies; (3) develop model programs in areas of great need, such as general
      public health, management, policy, prevention, environmental health and research,
      that in conjunction with a basic public health core, could satisfy the
      eligibility requirements of the American Board of Dental Public Health; (4)
      develop student loan forgiveness programs for dentists and dental hygienists
      working in public health; and (5) develop additional credential recognition
      programs for dental public health workers.

PMID- 9661107
TI  - History of federal legislation in health professions educational assistance in
      dental public health, 1956-97.
AB  - Health professions education assistance in dental public health has been
      congressionally authorized in one form or another during the last four decades.
      The US Department of Health and Human Services (and its predecessor, the
      Department of Health, Education, and Welfare) has been a focal point for managing
      these federal programs. This report tracks the history of relevant national
      legislation, beginning in the 1950s with the Health Amendment Acts of 1956 and
      continuing most recently with the Health Professions Education Extension
      Amendments of 1992. The number of dental public health professionals trained and
      available to provide expertise and leadership to improve community oral health
      status has been tied to the presence and intensity of federal programming in this
      area.

PMID- 9661106
TI  - Dental public health for the 21st century: implications for specialty education
      and practice.
AB  - A panel of public health practitioners sponsored by the Health Resources and
      Services Administration met December 6-8, 1994, to examine current roles and
      responsibilities for dental public health workers and to recommend changes in
      education and training to meet challenges posed by an evolving health care
      system. Overall, at least the same number, if not more, dental public health
      personnel will be needed in the future. While some new roles were identified, the
      panel felt that only small numbers of personnel will be needed to fill these new
      roles. Not all of these roles necessarily require a dental degree. The panel felt
      that a need exists for more academicians for dental schools, schools of public
      health, dental public health residencies, and dental hygiene programs; oral
      epidemiologists and health services researchers; health educators; and
      specialists in utilization review/outcomes assessment, dental informatics,
      nutrition, program evaluation, and prevention. To meet these personnel needs: (1)
      dental public health residency programs should be structured to meet the
      educational needs of working public health dentists with MPH degrees through on
      the-job residency programs; (2) the standards for advanced specialty education
      programs in dental public health should be made sufficiently flexible to include
      dentists who have advanced education and the requisite core public health
      courses; (3) flexible MPH degree programs must be available because of the rising
      debt of dental students and the decreased numbers of graduating dentists; (4)
      loan repayment should be available for dentists who have pursued public health
      training and are working in state or local health departments; and (5) standards
      for advanced education in dental public health should be developed for dental
      hygienists.

PMID- 9661108
TI  - Dental public health postdoctoral education: a survey on the status of funding
      and career opportunities.
AB  - OBJECTIVES: This paper reports the results of a survey to determine the
      consequences of budget reductions on the status of dental public health
      postdoctoral training in the United States, and opinions of experts in education
      and practice regarding career opportunities in dental public health. METHODS: A
      survey was mailed to 154 dental and public health education and service
      institutions. RESULTS: Most respondents (74 of 103; 72%) agreed that training
      opportunities depend on funding, and 73 percent (n = 75) expressed the view that
      more dental public health specialists are needed. Respondents reported that
      funding for current dental public health master's degree and residency programs
      is less than satisfactory. Respondents involved in training of dental public
      health professionals held marginally statistically significant different opinions
      regarding career opportunities than those who were not involved. No significant
      differences in opinions of respondents existed by type of institution.
      CONCLUSION: With decreased numbers of dental graduates, improved funding for
      dental public health programs will be critical, particularly at the specialty
      entry level, to ensure that adequate numbers of specialists are trained and
      available to meet the oral health needs of all the US population.

PMID- 9661109
TI  - Academic dental public health diplomates: their distribution and recommendations
      concerning the predoctoral dental public health faculty.
AB  - OBJECTIVE: The purpose of this study was to assess the representation of
      academically based diplomates of the American Board of Dental Public Health
      (ABDPH) and to identify their perceptions on the training of dental public health
      predoctoral faculty. METHODS: Data were collected by a mailed, self-administered,
      13-item questionnaire. The population was the 48 diplomates of the ABDPH as of
      March 1997 associated with academic institutions. RESULTS: Twenty of the 55 US
      dental schools had a diplomate of the ABDPH with a mean of 1.8 diplomates per
      school with a diplomate. An average of 4.5 full-time faculty members per school
      were associated with teaching dental public health. A master's degree in public
      health (MPH) was the most frequently suggested educational requirement for dental
      public health faculty. Continuing education courses were training needs perceived
      for dental public health faculty. The lack of time, money, and incentives, along
      with perceived rigidity of requirements for board certification, were reported as
      major barriers for faculty becoming dental public health board certified.
      CONCLUSIONS: Numerous challenges confront the development of a strong dental
      public health presence in US dental schools. These challenges include, among
      others, insufficient numbers of academic dental public health specialists and
      insufficient motivations to encourage promising candidates to pursue specialty
      status.

PMID- 9661110
TI  - Response to the IOM Committee Report on the Future of Dental Education--"Dental
      Education at the Crossroads: Challenges and Change".

PMID- 9661111
TI  - AAPHD Policy Statement on the IOM's Report: Dental Education at the Crossroads:
      Challenges and Change.

PMID- 9661112
TI  - Summary of report of IOM Committee on the Future of Dental Education, "Dental
      Education at the Crossroads: Challenges and Change".

PMID- 9661113
TI  - The development of competencies for specialists in dental public health.
AB  - This paper describes the process of developing new competency statements and
      performance indicators for the specialty of dental public health. These
      competencies help define the specialty and provide a base for educational
      curricula and the specialty board examination. The process included a survey of
      four target groups: all board members, all directors or co-directors of advanced
      education programs in dental public health, people who had become diplomates in
      the last three years, and all students currently enrolled in dental public health
      programs. Many constituencies were represented at the workshop, conducted in May
      1997, to develop the competency document. After the workshop, the document
      underwent a series of review activities.

PMID- 9661114
TI  - Preamble to the competency statements for dental public health.

PMID- 9661115
TI  - Dental public health competencies.

PMID- 9661116
TI  - American Association of Public Health Dentistry. Code of ethics and standards of
      professional conduct.

PMID- 9661117
TI  - Maximal parenteral glucose oxidation in hypermetabolic young children.

PMID- 9661118
TI  - Dear Miss Milk Toast.

PMID- 9661119
TI  - Metabolic effects of adjuvant recombinant human growth hormone in patients with
      continuing sepsis receiving parenteral nutrition.
AB  - BACKGROUND: Adjuvant growth hormone is advocated for treating the catabolism of
      prolonged sepsis not corrected by parenteral nutrition alone. METHODS: An open
      study was performed in which eight patients whose postabsorptive resting energy
      expenditure was persistently elevated by a mean of 19% as a result of continuing
      sepsis were randomized to receive 0.03 or 0.06 mg/kg recombinant human growth
      hormone (rhGH) each evening for 7 days adjuvant to total parenteral nutrition.
      Plasma concentrations of growth hormone, insulin, insulin-like growth factors 1
      and 2 (IGF-1 and -2) and their binding proteins IGFBP-1 and -3 were measured
      before and after rhGH, and their relationship with rates of whole-body protein
      turnover was determined in the morning in the postabsorptive state by using L-[1
      13C]leucine. RESULTS AND CONCLUSIONS: Before rhGH, the patients were
      hyperinsulinemic (mean, 44.4 mU/L) but had growth hormone levels within the
      normal range (< 10 mU/L). After the seventh dose of rhGH, nocturnal growth
      hormone concentrations rose to a mean of 35.3 +/- 26.1 and 61.3 +/- 21.05 mU/L
      for the low and higher dose groups, respectively. Morning IGF-1 concentrations
      showed a small increase during treatment, rising from a mean of 241.3 +/- 99.0 to
      301.7 +/- 167.3 ng/mL for the low-dose group and from 214.5 +/- 74.6 to 294.1 +/-
      116.9 ng/mL for the higher-dose group. IGF-2 increased slightly by 89 +/- 39 and
      75 +/- 49 ng/mL for the low and higher doses, respectively. IGFBP-1 and -3 and
      insulin did not change. The balance between nitrogen input and urinary urea
      nitrogen increased after rhGH by a mean of 5.3 g/d with no differences between
      the two dosage groups (4.74 +/- 1.56 g/d for the higher dose, 5.94 +/- 3.70 g/d
      for the lower). No significant changes were observed in whole-body protein
      turnover after a 1-week course of rhGH.

PMID- 9661120
TI  - Preoperative oral supplement with immunonutrients in cancer patients.
AB  - BACKGROUND: Early postoperative enteral nutrition with immune-enhancing
      supplements has helped to restore immune function and reduce infectious
      complications in patients with cancer undergoing major gastrointestinal
      operations. The aim of this study was to evaluate the effectiveness of similar
      supplements (containing arginine and arginine plus omega-3 fatty acids) given
      preoperatively for 1 week before cancer surgery. METHODS: In this randomized,
      double-blinded study, patients scheduled to undergo elective resection of upper
      gastrointestinal tumors were given one of three different oral liquid
      supplemental diets (control, arginine, arginine plus omega-3 fatty acids) to be
      taken each day for 7 days before surgery. Blood samples were obtained upon
      enrollment, on the morning of surgery, and on postoperative day 1 for analysis of
      immunologic function. RESULTS: Mean serum ornithine (a metabolite of arginine)
      levels were significantly higher compared with controls, but no significant
      increase in mean serum arginine levels was noted on the morning of surgery for
      those patients who received arginine as part of the supplement. In conjunction
      with these findings, there were no differences among groups in mean lymphocyte
      mitogenesis, mean peripheral blood mononuclear cell production of cytokines, or
      clinical outcomes. CONCLUSIONS: Use of oral liquid supplements in this fashion
      did not improve lymphocyte proliferation or monocyte functions in patients with
      cancer undergoing major surgery.

PMID- 9661121
TI  - Maximal parenteral glucose oxidation in hypermetabolic young children: a stable
      isotope study.
AB  - BACKGROUND: During periods in which nutrition support of critically ill young
      children must be parenteral, glucose infusions are administered at up to 10 or
      more mg.kg-1.min-1 to meet predicted energy needs. However, data in adults
      suggest that such high glucose loads exceed the ability to oxidize glucose in the
      hormonal milieu that characterizes critical illness. The purpose of this study
      was to determine if these high glucose loads are oxidized by critically ill young
      children. METHODS: Ten young children with serious burns were enrolled in a
      stable isotope study of glucose metabolism. These five boys and five girls were
      an average age of 5.2 years (range, 1 to 11 years), weight of 18.4 kg (range, 10
      to 31 kg) and burn size of 51.6% of the body surface (range, 35% to 86%). During
      clinically required episodes of parenteral nutrition support, we used the
      [13C6]glucose tracer to assess the efficacy of glucose oxidation at both 5 and 8
      mg.kg-1.min-1. Serum glucose was recorded and indirect calorimetry was performed.
      RESULTS: The fraction of exogenous glucose oxidation fell from 59% +/- 5% to 47%
      +/- 5% (p < .05). Although there was a significantly increased level of total
      glucose oxidation (3.2 to 3.8 mg.kg-1.min-1), this increment (29% +/- 9%) was
      accompanied by a significant decrease in the efficiency of energy production,
      because the bulk of the additional glucose above 5 mg.kg-1.min-1 was not being
      oxidized. Plasma glucose concentration did not change (145 +/- 4 vs 137 +/- 4
      mg/dL, p < .01) and whole-body expired gas respiratory quotients remained
      consistent with a mixed fuel oxidation, implying that there exists an increased
      rate of exogenous glucose uptake by tissues in nonoxidative pathways.
      CONCLUSIONS: Maximum glucose oxidation in severely burned children occurs at
      intakes approximating 5 mg.kg-1.min-1. Exogenous glucose in excess of this amount
      enters nonoxidative pathways and is unlikely to improve energy balance. Clinical
      markers such as serum glucose levels or expired respiratory quotient may not
      detect inefficient glucose utilization.

PMID- 9661122
TI  - Use of intravenous lipids in critically ill patients with sepsis without and with
      hepatic failure.
AB  - BACKGROUND: Fat is the preferred energy fuel both in patients with sepsis and
      with hepatic failure. Thus lipid emulsions should serve as an ideal nutritional
      substrate in parenteral nutrition. However, previous studies have generated
      conflicting results on the utilization of artificial lipids in these disease
      states, and systematic studies in critically ill patients with combined organ
      dysfunctions and additional complications are lacking. We compared the
      elimination, hydrolysis, and oxidation of a 20% lipid emulsion in critically ill
      patients on respiratory support with sepsis and with sepsis plus hepatic failure
      and in healthy control subjects. SETTING: Medical critical care unit of a
      university hospital. SUBJECTS AND METHODS: Eight critically ill patients with
      sepsis, 8 patients with sepsis and decompensated chronic hepatic failure, and 10
      healthy volunteers were investigated. Elimination and hydrolysis was evaluated
      during constant i.v. infusion of 4.5 mg.kg body wt-1.min-1 of triglycerides
      during 120 minutes. Concentrations of plasma triglycerides, free fatty acids, and
      glycerol were measured, and elimination parameters were analyzed from plasma
      curves of triglycerides by using a two-compartment model. Resting energy
      expenditure and substrate oxidation were measured by indirect calorimetry.
      RESULTS: In patients with sepsis without and with hepatic failure the rise in
      plasma triglycerides was blunted and the clearance of triglycerides was enhanced
      by 20% and 40% (p < .05), respectively, compared with healthy controls. Basal
      free fatty acid concentrations were elevated, and the rise of free fatty acids
      and glycerol was comparable to healthy subjects. Energy expenditure was increased
      and lipid oxidation (as fraction of total energy expenditure) was slightly
      elevated in both patient groups; the rise in lipid oxidation during lipid
      infusion was comparable to controls. No side effects or impairment of gas
      exchange was seen. CONCLUSIONS: In a clinically relevant dosage range, the
      utilization of an i.v. lipid emulsion, the elimination and hydrolysis of
      triglycerides, and the lipid oxidation is not impaired in ventilated critically
      ill patients with sepsis or sepsis and chronic hepatic failure. Lipid emulsions
      thus are efficiently metabolized in critically ill patients with combined organ
      dysfunctions and associated sepsis.

PMID- 9661123
TI  - Glutamine enhances gut glutathione production.
AB  - BACKGROUND: The gastrointestinal tract is recognized as having important
      metabolic functions. This study examined gut glutathione (GSH) extraction and the
      effect of supplemental oral glutamine (GLN) on gut GSH fractional release.
      METHODS: Healthy female Fisher-344 rats weighing approximately 150 to 200 g were
      pair-fed chow and supplemented by gavage with 1 g/kg/d GLN or an isonitrogenous
      amount of Freamine (McGaw, St. Louis, MO). Rats were sacrificed at 6 weeks.
      Arterial and portal blood was assayed for GLN and GSH content. The gut GLN and
      GSH extractions were calculated. RESULTS: The gut GLN fractional uptake was
      increased by approximately 50%, and there was a near threefold increase in gut
      GSH fractional release in the GLN-supplemented group. CONCLUSIONS: The discovery
      of gut's role as a major producer of GSH may give insight into why feeding via
      the gut rather than by the venous route is so important. Supplemental oral GLN
      further enhances GLN extraction as well as GSH fractional release in the gut.

PMID- 9661124
TI  - N-acetylcysteine protects from glutathione depletion in rats exposed to
      hyperoxia.
AB  - BACKGROUND: N-acetylcysteine (NAC) may protect against oxidative injury by
      providing cysteine for glutathione (GSH) biosynthesis or by direct reactions with
      electrophiles. We have recently shown that hyperoxic exposure of rats prior to
      liver perfusion is associated with significant decreases in hepatic GSH and
      significant changes in biliary amino acid concentrations. We hypothesized that
      NAC administration during hyperoxic exposure would prevent depletion of hepatic
      GSH by providing cysteine for GSH biosynthesis. METHODS: NAC was administered
      during two conditions known to induce GSH depletion: hyperoxic exposure and
      biochemical inhibition of GSH synthesis using buthionine sulfoximine (BSO). After
      48 hours, GSH concentrations in bile, liver and perfusate and biliary amino acid
      concentrations were determined using isolated perfused liver preparations.
      RESULTS: Administration of NAC to rats maintained in normoxic or hyperoxic
      conditions, prior to liver perfusion, resulted in dose-dependent increases in GSH
      concentrations in bile, liver and perfusate, increases in bile flow rates and
      changes in biliary amino acid concentrations. When BSO was given concurrently
      with NAC in normal or hyperoxic conditions, these effects were not observed, and
      oxidant stress was evident. CONCLUSIONS: NAC prevents oxidant stress during
      hyperoxic exposure, most likely by supplying cysteine as a precursor for GSH
      synthesis.

PMID- 9661125
TI  - Central venous catheters versus peripheral veins for sampling blood levels of
      commonly used drugs.
AB  - BACKGROUND: Our objective was to compare the accuracy of drug levels in blood
      samples obtained from central venous catheters with those from peripheral blood
      samples taken to monitor various drug levels. METHODS: Pediatric patients with
      central venous catheters receiving aminoglycosides, vancomycin, or cyclosporine
      had central and peripheral blood samples obtained within 5 minutes of each other
      and analyzed simultaneously. We ascertained how well blood levels from central
      venous catheters compared with those from peripheral blood (the criterion
      standard). RESULTS: There were no clinically significant differences between
      central and peripheral values for amikacin, gentamicin, tobramycin, and
      vancomycin (both peaks and troughs). Preliminary data indicated that oral
      cyclosporine can be monitored via central venous catheter. In contrast, there was
      poor agreement between peripheral and central values when cyclosporine was
      administered by IV. CONCLUSIONS: Amikacin, gentamicin, tobramycin, vancomycin,
      and probably oral cyclosporine can be monitored accurately via central venous
      catheter. In contrast, IV cyclosporine should be monitored via peripheral blood.

PMID- 9661126
TI  - Percutaneous endoscopic gastrostomy for nutrition support in pregnancy associated
      with hyperemesis gravidarum and anorexia nervosa.
AB  - BACKGROUND: Pregnant women with hyperemesis gravidarum (HEG) or anorexia nervosa
      are at high risk of developing malnutrition and adverse fetal outcome. Providing
      adequate nutrition support is the mainstay of therapy in these patients. Because
      of potential complications associated with total parenteral nutrition (TPN),
      enteral nutrition support is the preferred route. METHODS: We describe the first
      two reported cases of percutaneous endoscopic gastrostomy (PEG) placement in two
      conscious pregnant women who could not tolerate oral feedings because of severe
      anorexia nervosa and HEG, respectively. RESULTS: PEG was placed safely and
      provided adequate enteral nutrition in both patients, resulting in favorable
      maternal and fetal outcomes. CONCLUSIONS: Our observation is the first
      demonstration that PEG may be a safe and effective alternative to TPN in selected
      pregnant women with HEG or anorexia nervosa who have failed conventional
      treatment.

PMID- 9661127
TI  - Taurolidine 2% as an antimicrobial lock solution for prevention of recurrent
      catheter-related bloodstream infections.
AB  - BACKGROUND: This case report describes our preliminary data on the use of
      taurolidine as a lock technique. Taurolidine is a novel antimicrobial agent that
      has found a niche in Europe for prevention of bacteremia in home parenteral
      nutrition (HPN) patients who have multiple catheter-related blood-stream
      infections. METHODS: A 29-year-old male with short bowel syndrome was admitted 18
      times in 9 years for treatment of Gram-positive, Gram-negative, and yeast
      associated catheter-related bloodstream infections. Management consisted of
      conventional antibiotic treatment in accordance with blood culture and
      sensitivity results as well as catheter removal in 10 cases. Ten months before
      the last infection, the patient was instructed to instil 1.5 mL taurolidine 2%
      daily into his central line after finishing his HPN infusion and has continued to
      do so 2 years to date. RESULTS: The incidence of catheter-related bloodstream
      infections decreased from 8.5 to 1.5 infections per 1000 catheter days.
      CONCLUSIONS: These data support previous observations made outside North America
      and suggest that taurolidine may prove to be an effective and safe antimicrobial
      agent for the prevention of recurrent catheter-related bloodstream infections.

PMID- 9661128
TI  - Osteomyelitis of the clavicle after subclavian vein catheterization.
AB  - Osteomyelitis of the clavicle or the sternoclavicular joint is a rare
      complication of subclavian vein catheterization. Soft tissue infections around
      the puncture site occur frequently and respond well to topical and antibiotic
      treatment. If symptoms persist for several weeks, osteomyelitis or
      sternoclavicular pyo-arthrosis should be considered. Bone and gallium
      scintigraphy scans and computerized tomography scans are helpful diagnostic
      measures.

PMID- 9661129
TI  - Growth hormone increases and IGF-I reduces the response to Escherichia coli
      infusion in injured pigs.

PMID- 9661130
TI  - Effect of energy loads on nitrogen balance.

PMID- 9661131
TI  - Transforming growth factor-beta in renal disease.
AB  - An extensive number of animal and clinical studies indicate that transforming
      growth factor-beta (TGF-beta s) play an important role in inflammatory and
      fibrotic diseases, including renal fibrosis. Recent mouse models harboring
      genetically engineered alterations in TGF-beta pathways reveal complicated
      mechanisms of regulation of TGF-beta activity in vivo. The purpose of this review
      is to present recent advances relevant to our understanding of the TGF-beta
      signaling system in renal physiology and pathophysiology.

PMID- 9661132
TI  - Glomerular endothelial cell injury mediated by shiga-like toxin-1.
AB  - The hemolytic uremic syndrome is an important cause of acute renal failure and is
      often associated with prior infection with enterotoxigenic strains of Escherichia
      coli. Significant pathologic changes in the glomerulus include endothelial cell
      swelling, detachment, and intravascular coagulation. We investigated the
      potential pathogenetic mechanisms of this disease by exposing cultured rat
      glomerular endothelial cells to shiga-like toxin 1 (SLT-1). Glomerular
      endothelial cell viability and protein synthesis were not affected by 10(-9) M
      SLT-1. Synthesis and release of thromboxane (Tx) A2, measured as the stable
      metabolite TxB2, and of 12-(S)-HETE were each increased 1.6 +/- 0.1 fold (p <
      0.05). No change was observed in the production of PGE2 or 6-keto-PGF1 alpha, the
      active metabolite of PGI2. SLT-1 (10(-9) M) significantly increased cell
      retraction and the formation of gaps in the glomerular endothelial cell monolayer
      for up to 6 h following exposure. A similar effect was seen with 0.1 microM 12
      (S)-HETE. SLT-1 and 0.01 microM 12-(S)-HETE also significantly decreased adhesion
      of glomerular endothelial cells to fibronectin (75 +/- 4 and 65 +/- 2% of
      control, respectively; p < 0.001) and laminin (81 +/- 5 and 67 +/- 4% of control,
      respectively; p < 0.01). These results support a role for SLT-1 in the production
      of the pathologic changes seen in the hemolytic uremic syndrome through
      stimulation of production of procoagulant, vasoconstrictor arachidonic acid
      metabolites with potential to produce endothelial injury and through alterations
      in glomerular endothelial cell adhesion to components of the glomerular basement
      membrane.

PMID- 9661133
TI  - Effects of chronic nitric oxide synthase inhibition on renal function and
      histology in polycythemic rats.
AB  - Augmented endogenous nitric oxide (NO) production may ameliorate derangement of
      renal functions or glomerular damage in polycythemia. To investigate this
      possibility, we examined the effect of NO synthase inhibition with N omega-nitro
      L-arginine methyl ester (L-NAME; 50 mg/dl in drinking water) on renal functions
      and histology in heminephrectomized Sprague-Dawley rats treated for 4 weeks with
      recombinant human erythropoietin (rh-EP; 500 IU/kg on alternate days). L-NAME
      elevated the blood pressure which was aggravated by concomitant rh-EP and was
      ameliorated by treatment with a nonpeptide angiotensin type 1 receptor blocker
      (CV116; 60 mg/kg in chow). The hematocrit level was prominently increased by rh
      EP. The glomerular filtration rate was impaired by L-NAME alone, but was
      maintained by concomitant administration of rh-EP or CV116. Micropuncture
      experiments revealed that the glomerular capillary pressure was similarly
      elevated by L-NAME alone or in combination with rh-EP. L-NAME significantly,
      although not prominently, aggravated glomerular sclerosis observed with rh-EP
      alone, and concomitant CV116 ameliorated the glomerular damage. These results
      suggest that, in polycythemia, enhanced NO production buffers the glomerular
      damage, and the balance between NO and angiotensin II may play an important role
      in maintaining renal function and glomerular structure.

PMID- 9661134
TI  - Effects of the AT1 antagonist HR 720 in comparison to losartan on stimulated
      sympathetic outflow, blood pressure, and heart rate in pithed spontaneously
      hypertensive rats.
AB  - It has been demonstrated in isolated organs that angiotensin II mediates
      catecholamine release via presynaptically located AT1 receptor subtypes. In the
      present study, the relevance of AT1-mediated noradrenaline and adrenaline release
      in a whole-animal model, which reflects the peripherally sympathetic system
      (pithed rat), was investigated. Furthermore, the effects of a new AT1 antagonist,
      HR 720, are demonstrated with respect to its pre- and postsynaptic actions in
      comparison to the AT1 antagonist losartan. Dose-response curves to angiotensin II
      of blood pressure show a tenfold higher potency for HR 720 to compete for
      angiotensin II, thereby decreasing the maximum effects when compared with
      losartan. The electrically induced sympathetic outflow resulted in a dose
      dependent increase after angiotensin II infusions. It could markedly be reduced
      with both AT1 antagonists, whereby HR 720 again was ten times more potent than
      losartan. Neither with HR 720 nor with losartan an agonistic activity could be
      demonstrated. The results indicate an AT1 receptor subtype mediated release of
      catecholamines in a whole-animal model. HR 720 is ten times more potent than the
      AT1 antagonist losartan and acts in a noncompetitive manner.

PMID- 9661135
TI  - Atrial natriuretic peptide enhances IL-1 beta-stimulated nitric oxide production
      in cultured rat vascular smooth muscle cells.
AB  - OBJECTIVE: To elucidate the effect of atrial natriuretic peptide (ANP) on
      cytokine-induced nitric oxide (NO) production, we examined whether ANP affects IL
      1 beta-stimulated NO production and inducible NO synthase (iNOS) mRNA expression
      in cultured rat vascular smooth muscle cells (VSMC). METHODS: VSMC were incubated
      with test agents for 24 h. The nitrite concentration of the culture medium, a
      stable-end product of NO, was measured by the column reduction method. NOS mRNA
      expression was analyzed by Northern blotting. The intracellular cAMP content was
      measured by enzyme immunoassay. cAMP-dependent kinase (PKA) activity was
      determined by a PKA assay system. RESULTS: IL-1 beta stimulated nitrite
      production in VSMC. ANP (10 nM to 1 mM) enhanced the nitrite production and iNOS
      mRNA expression in the presence of IL-1 beta. Both 8-bromo-guanosine 3',5'-cyclic
      monophosphate (8-br-cGMP) and dibutylyl adenosine 3',5'-cyclic monophate enhanced
      IL-1 beta-induced nitrite production. The effects of these two nucleotide donors
      on the nitrite production were not additive, suggesting a common pathway. KT
      5720, an inhibitor of PKA, abolished the enhancement of nitrite production by ANP
      and 8-br-cGMP, while KT 5823, an inhibitor of cGMP-dependent protein kinase, did
      not inhibit the enhancement. In the in vitro assay 8-br-cGMP increased PKA
      activity. CONCLUSIONS: ANP and cGMP enhanced IL-1 beta-induced NO production in
      VSMC. PKA rather than PKG may be involved in the enhancement.

PMID- 9661136
TI  - Effects of diadenosine polyphosphates on systemic and regional hemodynamics in
      anesthetized rats.
AB  - Diadenosine polyphosphates (Ap4A, Ap5A, Ap6A) induce vasodilatation or
      vasoconstriction in various isolated vessels and influence central and peripheral
      hemodynamics. The influence of diadenosine polyphosphates on hemodynamics was
      studied in anesthetized rats in vivo. Mean arterial blood pressure (MABP) and
      heart rate (HR) measured in the carotid artery decreased with Ap4A, Ap5A, and
      Ap6A. Renal blood flow (RBF), femoral blood flow (FBF) and cardiac output (CO)
      were evaluated by an ultrasonic transit-time method. Renal superficial blood flow
      (RSBF) was measured by laser Doppler flowmetry. CO, RBF and RSBF were decreased
      initially by all three diadenosine polyphosphates. FBF was also slightly
      decreased. Total peripheral (TPR), renal (RVR) and femoral (FVR) vascular
      resistances were calculated. TPR was transiently increased by the dinucleotides
      following by a decrease. RVR and, to a lesser extent, FVR were also increased.
      These data show that diadenosine polyphosphates have effects on both the heart
      and the peripheral blood vessels. The effects on the heart and MABP were
      dominated by bradycardia and hypotension. In the kidney, diadenosine
      polyphosphates induced a predominant vascoconstriction. The effects on skeletal
      muscle blood flow were much smaller. Thus, the three diadenosine polyphosphates
      studied differ in the effects on heart and peripheral vessels.

PMID- 9661137
TI  - Na(+)-dependent and -independent amino acid transport systems in immortalized
      human kidney epithelial cells derived from the proximal tubule.
AB  - In the proximal tubule Na(+)-dependent (SDAT) and Na(+)-independent (SIAT) amino
      acid (AA) transporters are present. The effects of neutral, basic, and acidic AA
      on membrane voltage (Vm) of immortalized human kidney epithelial (IHKE-1) cells
      derived from the proximal tubule were examined using the slow whole-cell patch
      clamp technique. In the presence of Na+ AA depolarized Vm in a concentration
      dependent manner (0.05-5 mM) with Asp = Arg = Glu = 2Cys < Pro = Leu < Phe = AIB
      = Ala = Pro = Asn < Gly. In the absence of extracellular Na+ a decreased
      depolarization was seen with most neutral AA (Ala, Pro, Asn, Gly, Phe, and Leu),
      and the depolarization was increased with Asp, Glu, Arg, and 2Cys (1 mM each). In
      the absence of Na+ and a reduction in Cl- (5 mM) the depolarization by Arg was
      reduced. Unlike that predicted for transport by system b0,+ which exchanges
      neutral against dibasic amino acids, Leu does not hyperpolarize but depolarize Vm
      of IHKE-1 cells in the absence of extracellular Na+. After removal of Na+ (0 mM)
      and a reduction in Cl- (5 mM) in the extracellular solution, Leu or Glu
      hyperpolarized Vm, indicating that IHKE-1 cells possess two different SIAT
      systems, one Cl(-)-dependent and similar to system b0,+ and one novel Cl(-)
      dependent system, which might be a Cl-/AA exchanger and can be blocked by the Cl(
      )-channel blockers 5-nitro-2-(3-phenylpropylamino)-benzoate (10 microM) and 4,4'
      diisothiocyanostibene-2,2'-disulfonic acid (50 microM). B system-related AA
      transporters might be responsible for the C(-)-independent SIAT, since we were
      able to detect its signal by Northern blot analysis.

PMID- 9661138
TI  - Reduced urinary excretion of dopamine and metabolites in chronic renal
      parenchymal disease.
AB  - BACKGROUND: Chronic renal parenchymal diseases are accompanied by a progressive
      loss of tubular units endowed with the ability to synthesise dopamine from L-3,4
      dihydroxyphenylalanine (L-DOPA), and preliminary evidence has suggested that the
      urinary excretion of free dopamine may be reduced in these disorders. However, it
      is well recognized now that under in vitro conditions, dopamine newly synthesised
      in tubular epithelial cells undergoes extensive deamination to 3,4
      dihydroxyphenylacetic acid (DOPAC) by monoamine oxidase (MAO); a small amount of
      the amine is converted to homovanillic acid by both MAO and catechol-O
      methyltransferase (COMT) and a minor amount is methylated to 3-methoxytyramine.
      AIMS: The present study aimed at examining the relationship between renal
      function and daily urinary levels of L-DOPA, free dopamine and its main
      metabolites, DOPAC and homovanillic acid (HVA) in patients (n = 28) with chronic
      renal parenchymal disease, in conditions of controlled sodium, potassium and
      phosphate intake. The levels of 5-hydroxyindolacetic acid (5-HIAA) were also
      evaluated in the same cohort of patients. RESULTS: The patients were divided in
      two groups according to creatinine clearance (group 1, 39 +/- 6 ml/min/1.73 m2, n
      = 14; group 2, 139 +/- 6 ml/min/1.73 m2, n = 14). In patients of group 1, the
      urinary levels of L-DOPA, dopamine and DOPAC (in nmol/24 h) were significantly
      lower (60% reduction) than in patients in group 2 (L-DOPA, 134 +/- 36 vs. 308 +/-
      51; dopamine, 759 +/- 175 vs. 1,936 +/- 117; DOPAC 2,595 +/- 340 vs. 7,938 +/-
      833). Also, the urinary excretion of HVA in patients group 1 was significantly
      lower (40% reduction) than in patients of group 2 (17,434 +/- 2,455 vs. 27,179 +/
      2,271 nmol/24 h). By contrast, no significant difference was observed in daily
      urinary excretion of 5-HIAA between the two groups of patients (group 1,27,280 +/
      3,721 nmol/day; group 2, 28,851 +/- 2,854 nmol/day). A positive linear
      relationship was found in these 28 patients between the creatinine clearance and
      the daily urinary excretion of L-DOPA (r = 0.64, p < 0.001), free dopamine (r =
      0.83; p < 0.0001), DOPAC (r = 0.86; p < 0.0001) and HVA (r = 0.65; p < 0.002),
      but not with that of 5-HIAA (r = 0.14; ns). The Udopamine:L-DOPA and
      UDOPAC/dopamine ratios were found to be similar in both groups of patients
      whereas the UHVA/DOPAC ratios in patients of group 1 were found greater than in
      group 2 (p < 0.05). CONCLUSION: Patients suffering from chronic parenchymal
      disease with a compromised renal function present with a reduced activity of
      their renal dopaminergic system which correlates well with the degree of
      deterioration of renal function. The reduced urinary dopamine output in renal
      insufficiency is not attributable to enhanced metabolism of renal dopamine. We
      suggest that the urinary levels of DOPAC may represent a useful parameter for the
      assessment of renal dopamine synthesis.

PMID- 9661139
TI  - Angiotensin-converting enzyme gene polymorphism determines the antiproteinuric
      and systemic hemodynamic effect of enalapril in patients with proteinuric renal
      disease. Austrian Study Group of the Effects of Enalapril Treatment in
      Proteinuric Renal Disease.
AB  - Angiotensin-converting enzyme (ACE) inhibitors are known to reduce blood pressure
      and proteinuria in a variety of different glomerular diseases. Nonetheless, a
      marked interindividual difference in the efficacy of these agents exists. The
      activity of the ACE and therefore of the renin-angiotensin-aldosterone system
      (RAAS) has been shown to be under genetic influence. Patients with a deletion
      genotype at the intron 16 of the ACE gene have been shown to exhibit higher
      activity of plasmatic ACE when compared to patients with the insertion genotype.
      We therefore studied prospectively the hemodynamic and antiproteinuric effect of
      a 6-month therapy with enalapril in patients with biopsy-proven proteinuric
      glomerular diseases and the DD (n = 10) and ID/II (n = 26) genotype. Although
      patients with the DD genotype received a slightly higher dose of enalapril, blood
      pressure and proteinuria did not change significantly. However, both were
      significantly reduced in the II/ID group after 10 weeks and 6 months of therapy.
      Creatinine clearance decreased steadily in DD patients. In II/ID patients,
      creatinine clearance was reduced significantly after 10 weeks of therapy but
      increased again thereafter and the value at 6 months was again comparable to the
      one obtained in the DD patients. We conclude from our study that the ACE genotype
      influences the blood pressure-lowering and antiproteinuric effect of enalapril in
      patients with proteinuric glomerular disease.

PMID- 9661140
TI  - Ambulatory infusion of noradrenaline for long-term treatment of Shy-Drager
      syndrome.
AB  - A 70-year-old female patient with advanced Shy-Drager syndrome exhibited severe
      orthostatic hypotension, low serum catecholamine levels, and autonomic
      dysfunction. She was bedridden despite oral medication with fludrocortisone,
      etilefrin, dihydroergotamine, L-dopa, yohimbine, and amezinium methyl sulfate.
      Only intravenous application of noradrenaline (30 ng/kg/min) provided complete
      mobilization. After implantation of a port-a-cath system, intravenous
      noradrenaline treatment could be continued on an outpatient basis. Over the
      following 5 years, the patient was throughout sufficiently mobile and did not
      show any significant side effects of this treatment. However, during the 5th year
      she suffered from nonhemorrhagic brain stem infarction due to cerebral
      hypoperfusion after orthostatic stress in the absence of noradrenaline infusion.
      We conclude that ambulatory noradrenaline infusion is a new valuable tool for
      long-term treatment of advanced Shy-Drager syndrome.

PMID- 9661141
TI  - Fredric Stewart Fay. 1943-1997.

PMID- 9661142
TI  - New photoprotecting groups: desyl and p-hydroxyphenacyl phosphate and carboxylate
      esters.

PMID- 9661143
TI  - Synthesis, photochemistry, and biological characterization of photolabile
      protecting groups for carboxylic acids and neurotransmitters.

PMID- 9661144
TI  - New caged groups: 7-substituted coumarinylmethyl phosphate esters.

PMID- 9661145
TI  - Caged fluorescent probes.

PMID- 9661146
TI  - Biologically active peptides caged on tyrosine.
AB  - We have demonstrated the feasibility of preparing caged peptides by derivatizing
      a single amino acid side chain in peptides up to 20 amino acids long. Two
      peptides are illustrated whose activities are reduced by nearly 2 orders of
      magnitude using this caging approach. The specific strategy described here of
      derivatizing tyrosine side chains with a charged caging moiety should be
      generally applicable in the preparation of caged peptides that have a critical
      tyrosine residue (e.g., LSM1) or that have critical hydrophobic patches (e.g., RS
      20). Other amino acid side chains are also accessible via this caging strategy.
      Derivatives of threonine, serine, lysine, cysteine, glutamate, aspartate,
      glutamine, and asparagine can be prepared and site specifically inserted into
      peptides in an analogous manner. The caged peptides synthesized and purified by
      the methods described here are compatible with biological samples, including
      living cells, and have been used to demonstrate the central importance of
      calmodulin, MLCK, and, by inference, myosin II in ameboid locomotion in polarized
      eosinophil cells. Photoactivation of peptides within cells should provide a
      wealth of new information in future investigations by allowing specific protein
      activities to be knocked out in an acute and spatially defined way.

PMID- 9661147
TI  - Light-directed activation of protein activity from caged protein conjugates.

PMID- 9661148
TI  - Caged peptides and proteins by targeted chemical modification.

PMID- 9661149
TI  - Photocleavable affinity tags for isolation and detection of biomolecules.

PMID- 9661150
TI  - Synthesis and applications of heterobifunctional photocleavable cross-linking
      reagents.
AB  - This study designed, synthesized, and characterized a number of new
      heterobifunctional photocleavable cross-linking reagents that may be used to
      photomodulate the activity of proteins or to prepare caged fluorescent dyes.
      Biomolecules or fluorophores caged via a thiol group with the BNBASE reagent can
      be covalently linked to a second protein, ligand, or derivatized surface through
      the activated carboxyl group. Members of the new class of photocleavable cross
      linking reagent can be used to cage amino groups in the molecule of interest,
      which can then be covalently linked to a second molecule through the thiol
      reactive oxirane group. These crosslinking reagents may be used for the following
      applications: (1) to cage the activity of a protein by masking its active site
      with a second macromolecule, e.g., aminodextran; (2) to prepare a protein
      conjugate exhibiting an enhanced or new activity that is lost on irradiation with
      near-ultraviolet light, e.g., cross-linked actin dimer; (3) to target the caged
      compound to a specific site by cross linking to a specific antibody; (4) to
      attach the caged compound to a thiol or amino derivatized surface; and (5) to
      render the caged compound fluorescent in order to image or to quantify the yield
      of the photoactivation reaction.

PMID- 9661151
TI  - Flash lamp-based irradiation of caged compounds.

PMID- 9661152
TI  - Fourier transform infrared photolysis studies of caged compounds.
AB  - Time-resolved FTIR difference spectroscopy is a powerful tool for investigating
      molecular reaction mechanisms of proteins. In order to detect, beyond the large
      background absorbance of the protein and the water, absorbance bands of protein
      groups that undergo reactions, difference spectra have to be performed between a
      ground state and an activated state of the sample. Because the absorbance changes
      are small, the reaction has to be started in situ, in the apparatus, and in thin
      protein films. The use of caged compounds offers an elegant approach to initiate
      protein reactions with a nanosecond UV laser flash. Here, time-resolved FTIR and
      FT-Raman photolysis studies of the commonly used caged compounds, caged Pi, caged
      ATP, caged GTP, and caged calcium are presented. The use of specific isotopic
      labels allows us to assign the IR bands to specific groups. Because metal ions
      play an important role in many biological systems, their influence on FTIR
      spectra of caged compounds is discussed. The results presented should provide a
      good basis for further FTIR studies on molecular reaction mechanisms of energy or
      signal transducing proteins. As an example of such investigations, the time
      resolved FTIR studies on the GTPase reaction of H-ras p21 using caged GTP is
      presented.

PMID- 9661153
TI  - Use of caged nucleotides to characterize unstable intermediates by X-ray
      crystallography.

PMID- 9661154
TI  - Photoregulation of cholinesterase activities with caged cholinergic ligands.

PMID- 9661155
TI  - Caged substrates for measuring enzymatic activity in vivo: photoactivated caged
      glucose 6-phosphate.

PMID- 9661156
TI  - Investigation of charge translocation by ion pumps and carriers using caged
      substrates.

PMID- 9661157
TI  - Studies of molecular motors using caged compounds.

PMID- 9661158
TI  - Application of caged fluorescein-labeled tubulin to studies of microtubule
      dynamics and transport of tubulin molecules in axons.

PMID- 9661159
TI  - Two-photon activation of caged calcium with submicron, submillisecond resolution.

PMID- 9661160
TI  - Caged inositol 1,4,5-trisphosphate for studying release of Ca2+ from
      intracellular stores.

PMID- 9661161
TI  - Characterization and application of photogeneration of calcium mobilizers cADP
      ribose and nicotinic acid adenine dinucleotide phosphate from caged analogs.

PMID- 9661162
TI  - Applications of caged compounds of hydrolysis-resistant analogs of cAMP and cGMP.

PMID- 9661163
TI  - Caged probes for studying cellular physiology: application of o
      nitromandelyloxycarbonyl (Nmoc) caging method to glutamate and a Ca(2+)-ATPase
      inhibitor.

PMID- 9661164
TI  - Development and application of caged ligands for neurotransmitter receptors in
      transient kinetic and neuronal circuit mapping studies.

PMID- 9661165
TI  - Use of caged compounds in studies of the kinetics of DNA repair.

PMID- 9661166
TI  - Think royalties, not caps.

PMID- 9661167
TI  - Structural genomics: simply the next new thing--or is this it?

PMID- 9661168
TI  - Finding the substance behind the smoke: who is using biotechnology?

PMID- 9661169
TI  - Integrating information technology and drug discovery processes.

PMID- 9661170
TI  - Changing university roles in the century of biotechnology.

PMID- 9661171
TI  - The hydropathic binary code: a tool in genomic research?

PMID- 9661172
TI  - IGF in the clinic.

PMID- 9661173
TI  - Chloroplast-transgenic plants: panacea--no! Gene containment--yes!

PMID- 9661181
TI  - British Biotech fails to redeem itself.

PMID- 9661182
TI  - PE/TIGR provokes genome sequencing skeptics.

PMID- 9661183
TI  - Activists challenge FDA food policy.

PMID- 9661184
TI  - Despite size difference, Monsanto, AHP to merge.

PMID- 9661185
TI  - Concern mounts over Munich's BioRegio money.

PMID- 9661186
TI  - Genentech's anticancer Mab expected by November.

PMID- 9661187
TI  - Biotech-biotech company mergers puzzle investors.

PMID- 9661188
TI  - When blind is better: protein design by evolution.

PMID- 9661189
TI  - A freeze-dryer and a fertile imagination.

PMID- 9661190
TI  - From cows stem therapies?

PMID- 9661191
TI  - Artificial blood: ancient dream, modern enigma.

PMID- 9661192
TI  - Swell plant parasite plays host to chemical reactions.

PMID- 9661193
TI  - Structural genomics: bioinformatics in the driver's seat.

PMID- 9661194
TI  - Developmental biology's impact on drug development.

PMID- 9661195
TI  - The emergence of flow cytometry for sensitive, real-time measurements of
      molecular interactions.
AB  - The analysis of macromolecular interactions is an essential element of biomedical
      research. Flow cytometry is uniquely capable of making sensitive and quantitative
      measurements of molecular interactions. These measurements can be made in real
      time with subsecond kinetic resolution using purified biomolecules or living
      cells. Combined with automated sample handling, these features make flow
      cytometry a versatile and robust technology for the analysis of molecular
      interactions.

PMID- 9661196
TI  - Development of normal mice from oocytes injected with freeze-dried spermatozoa.
AB  - Freeze-dried mouse spermatozoa are all motionless and dead in the conventional
      sense. When injected into oocytes, however, their nuclei can support normal
      embryonic development even after three month preservation in a dried state.
      Although the freeze-drying protocol reported here will need further improvement,
      the results suggest that it may be possible to store the male genomes at room
      temperature.

PMID- 9661197
TI  - Transgenic bovine chimeric offspring produced from somatic cell-derived stem-like
      cells.
AB  - We have developed a method, using nuclear transplantation, to produce transgenic
      embryonic stem (ES)-like cells from fetal bovine fibroblasts. These cells, when
      reintroduced into preimplantation embryos, differentiated into derivatives from
      the three embryonic germ layers, ectoderm, mesoderm, and endoderm, in 5-month-old
      animals. Six out of seven (86%) calves born were found to be chimeric for at
      least one tissue. These experiments demonstrate that somatic cells can be
      genetically modified and then de-differentiated by nuclear transfer into ES-like
      cells, opening the possibility of using them in differentiation studies and human
      cell therapy.

PMID- 9661198
TI  - Production of biologically active salmon calcitonin in the milk of transgenic
      rabbits.
AB  - Salmon calcitonin (sCT) is an example of one of the many bioactive peptides that
      require amidation of the carboxy terminus for full potency. We describe a method
      for the production of amidated sCT in the mammary gland of transgenic rabbits.
      Expression of a fusion protein comprising human alpha lactalbumin joined by an
      enterokinase cleavable linker to sCT was directed to the mammary gland under the
      control of the ovine beta lactoglobulin promoter. C-terminal amidation in vivo
      was achieved by extending the sCT by a single glycine residue that provides a
      substrate for endogenous amidating activity in the mammary gland. Full
      characterization of the released sCT demonstrated it to be equivalent to
      synthetic standard in terms of structure, purity, and potency.

PMID- 9661199
TI  - Man-made cell-like compartments for molecular evolution.
AB  - Cellular compartmentalization is vital for the evolution of all living organisms.
      Cells keep together the genes, the RNAs and proteins that they encode, and the
      products of their activities, thus linking genotype to phenotype. We have
      reproduced this linkage in the test tube by transcribing and translating single
      genes in the aqueous compartments of water-in-oil emulsions. These compartments,
      with volumes close to those of bacteria, can be recruited to select genes
      encoding catalysts. A protein or RNA with a desired catalytic activity converts a
      substrate attached to the gene that encodes it to product. In other compartments,
      substrates attached to genes that do not encode catalysts remain unmodified.
      Subsequently, genes encoding catalysts are selectively enriched by virtue of
      their linkage to the product. We demonstrate the linkage of genotype to phenotype
      in man-made compartments using a model system. A selection for target-specific
      DNA methylation was based on the resistance of the product (methylated DNA) to
      restriction digestion. Genes encoding HaeIII methyltransferase were selected from
      a 10(7)-fold excess of genes encoding another enzyme.

PMID- 9661200
TI  - Improved properties of FLP recombinase evolved by cycling mutagenesis.
AB  - The site-specific recombinases FLP and Cre are useful for genomic engineering in
      many living systems. Manipulation of their enzymatic properties offers a means to
      improve their applicability in different host organisms. We chose to manipulate
      the thermolability of FLP recombinase. A lacZ-based recombination assay in
      Escherichia coli was used for selection in a protein evolution strategy that
      relied on error-prone PCR and DNA shuffling. Improved FLP recombinases were
      identified through cycles of increasing stringency imposed by both raising
      temperature and reducing protein expression, combined with repetitive cycles of
      screening at the same stringency to enrich for clones with improved fitness. An
      eighth generation clone (termed FLPe) showed improved properties in E. coli, in
      vitro, in human 293- and mouse ES-cells.

PMID- 9661201
TI  - Enhanced degradation of polychlorinated biphenyls by directed evolution of
      biphenyl dioxygenase.
AB  - Biphenyl dioxygenases (BP Dox) from different organisms, which are involved in
      the initial oxygenation and subsequent degradation of polychlorinated biphenyls
      (PCB), are similar in structure but have different functions. The large subunit
      of BP Dox, encoded by the bphA1 gene, is crucial for substrate selectivity. Using
      the process of DNA shuffling, we randomly recombined the bphA1 genes of
      Pseudomonas pseudoalcaligenes KF707 and Burkholderia cepacia LB400 and selected
      for genes that expressed proteins with altered function. Upon expression in
      Escherichia coli, some of these evolved genes exhibited enhanced degradation
      capacity, not only for PCB and related biphenyl compounds, but for single
      aromatic hydrocarbons such as benzene and toluene, which are poor substrates for
      the original BP Dox.

PMID- 9661202
TI  - Polyhemoglobin-superoxide dismutase-catalase as a blood substitute with
      antioxidant properties.
AB  - Polyhemoglobin-superoxide dismutase-catalase is designed to function as an oxygen
      carrier with antioxidant properties. This is based on cross-linking hemoglobin
      with superoxide dismutase and catalase (PolyHb-SOD-CAT). This study describes the
      structural and antioxidant properties of this solution. Our studies show that
      superoxide dismutase and catalase retain their enzymatic activity following
      glutaraldehyde polymerization with 8:1 and 16:1 glutaraldehyde:hemoglobin ratio.
      We have analyzed the optimal SOD/CAT ratios to prevent oxidation of hemoglobin in
      the presence of oxygen free radicals. The circulation half-life of crosslinked
      hemoglobin, SOD, and catalase in Sprague-Dawley rats correlates with the degree
      of polymerization as determined by high-performance molecular weight gel
      filtration. PolyHb-SOD-CAT decreases the formation of oxygen radicals compared
      with PolyHb in a rat intestinal ischemia-reperfusion model.

PMID- 9661203
TI  - Rate of reaction with nitric oxide determines the hypertensive effect of cell
      free hemoglobin.
AB  - Administration of extracellular hemoglobin-based oxygen carriers often induces
      mild increases in blood pressure. In order to test whether nitric oxide (NO)
      scavenging is responsible for the hypertensive effect, we constructed and tested
      a set of recombinant hemoglobins that vary in rates of reaction with NO. The
      results suggest that the rapid reactions of oxy- and deoxyhemoglobin with nitric
      oxide are the fundamental cause of the hypertension. The magnitude of the blood
      pressure effect correlates directly with the in vitro rate of NO oxidation.
      Hemoglobins with decreased NO-scavenging activity may be more suitable for
      certain therapeutic applications than those that cause depletion of nitric oxide.

PMID- 9661204
TI  - An efficient route to human bispecific IgG.
AB  - Production of bispecific IgG (BsIgG) by coexpressing two different antibodies is
      inefficient due to unwanted pairings of the component heavy and light chains. To
      overcome this problem, heavy chains were remodeled for heterodimerization using
      engineered disulfide bonds in combination with previously identified "knobs-into
      holes" mutations. One of the variants, S354C:T366W/Y349'C:T366'S:L368'A:Y407++
      +'V, gave near quantitative (approximately 95%) heterodimerization. Light chain
      mispairing was circumvented by using an identical light chain for each arm of the
      BsIgG. Antibodies with identical light chains that bind to different antigens
      were identified from an scFv phage library with a very restricted light chain
      repertoire for the majority (50/55) of antigen pairs tested. A BsIgG capable of
      simultaneously binding to the human receptors HER3 and cMpI was prepared by
      coexpressing the common light chain and corresponding remodeled heavy chains
      followed by protein A chromatography. The engineered heavy chains retain their
      ability to support antibody-dependent cell-mediated cytotoxicity as demonstrated
      with an anti-HER2 antibody.

PMID- 9661205
TI  - Building the proper foundation for genomics-based patents.

PMID- 9661206
TI  - Combinatorial chemistry.

PMID- 9661207
TI  - Comparing basic and clinical research: a dilemma.

PMID- 9661208
TI  - Spectacle lenses and emmetropization: the role of optical defocus in regulating
      ocular development.
AB  - The purpose of our investigation was to determine whether early ocular growth and
      refractive development was regulated by visual feedback in infant monkeys.
      Specifically, we examined the ability of infant monkeys to compensate for
      optically induced changes in the eye's refractive state and to recover from
      experimentally induced refractive errors. For moderate-powered anisometropic
      lenses, infants exhibited differential interocular axial growth rates that
      reduced the lens-induced refractive imbalance between the two eyes. Infants
      treated with equal-powered lenses over both eyes also showed compensating growth.
      For lens powers between approximately -3 and +6 D, the resulting refractive-error
      changes, which were primarily due to alterations in vitreous chamber growth
      rates, were well correlated with the effective refractive state produced by the
      treatment lenses. When the stimulus for altered eye growth was removed and the
      infants were provided unrestricted vision, monkey eyes consistently grew toward
      emmetropia. The remarkable degree of adaptability exhibited by the eyes of infant
      monkeys demonstrates that emmetropization in this higher primate is an active
      process that is regulated on a continuous basis by optical defocus. Consequently,
      early in life spectacle lenses by changing the eye's effective focus can
      predictably alter ocular growth and the refractive status of one or both eyes.

PMID- 9661209
TI  - Acuity perimetry and the sampling theory of visual resolution.
AB  - Visual resolution is limited by neural sampling of the retinal image everywhere
      in the visual field except the fovea, where optical limitations usually dominate.
      Consequently, measurements of resolution acuity may be interpreted as estimates
      of the spatial density of the mosaic of photoreceptors (in parafoveal retina) or
      ganglion cells (in peripheral retina) of the living human eye. Recent experiments
      in the basic visual sciences have paved the way for clinical applications of this
      approach to the problem of detecting the loss of photoreceptors and ganglion
      cells during aging and in a variety of retinal diseases.

PMID- 9661210
TI  - Screening for anisometropia in preschool children.
AB  - PURPOSE: A preschool vision screening program was reviewed to evaluate eccentric
      photoscreening (EP), visual acuity, and stereopsis in identifying anisometropia.
      METHODS: Patients referred by the screening were examined to assess efficacy of
      the three screening techniques in a population of preschool children. Testability
      and comparison of screening results to the classification of anisometropia (> or
      = 1 D) by retinoscopy obtained during a complete examination were evaluated.
      RESULTS: Although EP identified 94.5% of the anisometropic children as abnormal,
      only 27.8% were classified as anisometropic by EP. Of the anisometropic children,
      36.1% failed acuity, but only 19.4% failed based on a 2 line or greater
      interocular acuity difference. Stereopsis correctly identified only 7.3% of
      anisometropes as abnormal. CONCLUSIONS: The sensitivity of EP in identifying
      anisometropic children as abnormal was superior to acuity and stereopsis, yet its
      ability to identify anisometropia specifically was poor. Anisometropia of low
      magnitude or that masked by the dead zone of the EP system was frequently
      classified as isometropic. Altering the EP referral criterion and/or taking
      photographs through adequate power plus lenses may improve the sensitivity for
      specifically identifying anisometropia. However, caution must be exercised when
      using EP to examine the prevalence of anisometropia in a population or if used to
      screen for only amblyogenic refractive errors (i.e., anisometropia), because many
      anisometropes will be missed, resulting in inaccurate prevalence data and
      significant underreferrals.

PMID- 9661211
TI  - Naso-temporal asymmetry of spatial interactions in strabismic amblyopia.
AB  - PURPOSE: Naso-temporal asymmetries of visual acuity and contrast sensitivity have
      been reported in strabismic amblyopia and attributed to asymmetries of
      interocular suppression. In this study, we investigated the naso-temporal
      asymmetry of cortical spatial interactions in two strabismic amblyopes (one
      esotrope and one exotrope). METHODS: Length and width Westheimer functions were
      measured on both amblyopes at the 10 deg retinal eccentricity of both nasal and
      temporal visual fields. RESULTS: Spatial interactions in the two amblyopic eyes
      were more degraded in the temporal visual fields than in the nasal visual fields.
      A comparison with results from the preferred eyes suggested that this asymmetry
      was caused mainly by a loss of spatial interactions in the temporal visual fields
      of amblyopic eyes, with those in the nasal visual fields being normal.
      CONCLUSION: Our results suggest that intracortical connections underlying
      cortical spatial interactions might have been degraded by amblyopia. This
      degradation exists not only in the areas of the strabismic visual cortex
      responding to foveal stimuli but also in those responding to stimuli presented in
      the temporal visual fields.

PMID- 9661212
TI  - Effects of cue context on the perception of depth from combined disparity and
      perspective cues.
AB  - PURPOSE: In normal vision, stereoscopic cues are combined with perspective cues
      to provide veridical depth perception. The relative strengths of these depth
      cues, however, may be dependent upon context effects. We investigated the role of
      stimulus context on the interactions of binocular disparity, contrast, and size.
      METHODS: The subjects, four observers with normal stereoacuity and one stereo
      amblyope, discriminated far vs. near perceived depth of Gabor patches; feedback
      was based on the sign of binocular disparity. Depth discrimination functions were
      measured under conditions in which depth cues were consonant or in conflict.
      Three stimulus contexts were used: (1) variable disparity with fixed spatial
      frequency and contrast; (2) variable contrast with fixed spatial frequency and
      disparity; and (3) variable spatial frequency with fixed contrast and disparity.
      The effects of stimulus context were derived from comparisons of discrimination
      rates for identical stimuli across the three sets of conditions. RESULTS: In
      subjects with normal stereopsis, for disparities less than 2 arcmin, depth
      perception was dominated by contrast in contrast-varying sessions, or by size in
      spatial frequency-varying sessions. With larger disparities, depth perception
      became dependent on disparity, regardless of the contrast or spatial frequency of
      the test stimulus. The results for the stereo-amblyope showed much greater
      dependence on perspective cues and, in most cases, the transition from
      perspective- to disparity-based depth perception did not occur. CONCLUSIONS:
      These investigations demonstrate strong stimulus context effects and have
      important implications for the combination rules of stereoscopic and perspective
      cues in depth perception of normal and stereo-deficient subjects.

PMID- 9661213
TI  - Contact lens base curve prediction from videokeratography.
AB  - PURPOSE: To assess whether the contact lens to cornea-bearing relationship, as
      determined from the fluorescein pattern, can be predicted from videokeratography.
      METHODS: Nineteen non-rigid gas permeable (RGP) lens wearers were each tested for
      fluorescein patterns with a series of seven RGP contact lenses of different base
      curves, and compared to a theoretical estimate of the fitting relationship from
      videokeratography. The experimentally determined alignment lens was then compared
      to the theoretical alignment (TA) value as determined from the central curvature
      and eccentricity. RESULTS: The mean difference in lens choice between the TA and
      experimental alignment (EA) values was -0.01 +/- 0.04 mm and between the
      simulated keratometric (KA) readings and the EA choice was 0.11 +/- 0.05 mm.
      CONCLUSION: A knowledge of the eccentricity value from videokeratography allowed
      a better prediction of the base curve to cornea relationship than was provided by
      only a central corneal measurement.

PMID- 9661214
TI  - Accommodation and the third spatial harmonic.
AB  - PURPOSE: Mathews and Kruger recently reported that accommodative tracking of sine
      wave grating targets is best between 1 and 7 cpd. Their study suggests that the
      spatial third harmonic might not enhance the accommodative response if the
      fundamental is higher than roughly 2 cpd. This study tested the effect of adding
      the third harmonic with targets that included 1, 3, and 5 cpd fundamental sine
      wave gratings, compound gratings with the third harmonic of each of these
      fundamentals added in either peaks-add or peaks-subtract phase, as well as each
      third harmonic presented alone at one-third of the contrast of the fundamental
      gratings. METHODS: Accommodation was monitored continuously with a dynamic
      infrared optometer while the subject viewed the gratings in a Badal stimulus
      system. Dioptric vergence changed sinusoidally over a 2.00 or 0.50 D range at 0.2
      Hz. A Fast Fourier Transform extracted the amplitude and phase of each response
      at the temporal frequency of the stimulus. RESULTS AND CONCLUSIONS: The third
      harmonic enhanced the accommodative response only when the fundamental was 1 cpd.
      This was true at both amplitudes of target motion. This contradicts models that
      suggest that high spatial frequencies are used to refine the accommodative
      response. Second, the responses to the peaks-add and peaks-subtract phase
      conditions were essentially the same for each fundamental. This suggests that the
      effect of harmonics cannot be described by any simple linear relationship between
      the increased luminance gradient of the grating target and the accommodative
      response. Third, the accommodative response to gratings with a 5 cpd fundamental
      were smaller than the responses to gratings with the 3 cpd fundamental. This
      contradicts the gradient hypothesis of accommodative control inasmuch as the
      luminance gradient is steeper in the gratings with the 5 cpd fundamental.
      Alternatively, it seems that harmonics will enhance an accommodative response
      regardless of phase if they are effective accommodative stimuli on their own.

PMID- 9661215
TI  - 12-hydroxyeicosatetraenoic acid is a long-lived substance in the rabbit
      circulation.
AB  - 12-Hydroxyeicosatetraenoic acid (12-HETE) is one of the major metabolites formed
      from arachidonic acid in platelets. We have recently shown that the in vitro
      metabolism of 12-HETE by human leukocytes, with and without stimulation, is
      effectively inhibited by the addition of physiological concentrations of albumin,
      probably by sequestration of the compound. In the present paper, we have studied
      the in vivo metabolism of 12-HETE in the rabbit, using either [1-14C]- or
      [14C(U)]12-HETE. Distribution of radioactivity was followed in urine, plasma, and
      bile, as well as in a number of tissues. In most of the tissues examined, the
      hydrophilic radioactivity constituted more than 50% of the total radioactivity
      after 20 min. When the lipophilic fraction was analyzed, around 15% of the
      radioactivity was shown to be unesterified 12-HETE, and only a very minor part
      could be detected as metabolites. The dominating lipophilic compound in the
      circulation after i.v. administration of radiolabeled 12-HETE was at all time
      points (1-60 min.) the parent compound, as analyzed by HPTLC and HPLC. A
      comparison of the plasma metabolite profiles obtained when [1-14C]- and
      [14C(U)]12-HETE were used displayed almost identical patterns, thus indicating
      that beta-oxidized metabolites either were not formed or were rapidly removed
      from the circulation. The appearance of large amounts of water-soluble
      radioactivity with time supported the latter conclusion. Several minor
      metabolites were seen that chromatographed in the dihydroxy acid region as judged
      by HPLC and TLC. The major one of these compounds represented about 10% of the
      lipophilic plasma radioactivity after 60 min., while unmetabolized 12-HETE at
      this stage still represented about 30%. The metabolite had a polarity similar to
      12,20-dihydroxyeicosatetraenoic acid; however, when chromatographed together,
      these two compounds separated, indicating a different structure of the
      metabolite. Our findings are in agreement with in vitro data concerning the
      protective effect of albumin on the metabolism of 12-HETE and is the first
      extensive metabolic study of 12-HETE in vivo covering all metabolic possibilities
      involving the carbon skeleton.

PMID- 9661216
TI  - Effect of luteinizing hormone (LH), PGE2, 8-EPI-PGE1, 8-EPI-PGE2, trichosanthin,
      and pregnancy specific protein B (PSPB) on secretion of progesterone in vitro by
      corpora lutea (CL) from nonpregnant and pregnant cows.
AB  - Secretion of progesterone by Day 14 bovine corpora lutea (CL) of the estrous
      cycle and Day 200 CL of pregnancy was evaluated in vitro to determine what
      regulates secretion of progesterone by CL of pregnancy. Weights of Day 200 CL of
      pregnancy (4356 +/- 223 g) were heavier when compared to Day 14 CL of the estrous
      cycle of Brahman cows (3643 +/- 128 g; p < or = 0.05); however, both Day 14 and
      Day 200 minced CL slices secreted similar basal amounts of progesterone per unit
      mass (p > or = 0.05). Secretion of progesterone in vitro by Day 14 CL of the
      estrous cycle was increased at 4 and 8 h (p < or = 0.05) by 10 or 100 ng/mL
      luteinizing hormone (LH) and did not differ between doses (p > or = 0.05).
      Progesterone secretion in vitro by Day 200 CL of pregnancy was not increased (p >
      or = 0.05) by LH at 4 or 8 h. However, progesterone secretion in vitro by Day 14
      CL of the estrous cycle or Day 200 CL of pregnancy was increased (p < or = 0.05)
      at 4 h by 10 or 100 ng/mL PGE2, which did not differ by dose or reproductive
      status (p > or = 0.05). At 8 h, Day 14 CL of the estrous cycle secretion of
      progesterone in vitro was increased (p < or = 0.05) by both doses of PGE2 but
      only at 8 h by 100 ng/mL from Day 200 CL of pregnancy (p < or = 0.05). Secretion
      of progesterone in vitro was not affected (p > or = 0.05) by 10 or 100 ng/mL 8
      Epi-PGE1 or 8-Epi-PGE2 at 4 or 8 h from Day 14 CL of the estrous cycle or Day 200
      of pregnancy. Trichosanthin increased (p < or = 0.05) secretion of progesterone
      in vitro by 10 ng/mL at 4 h and at 8 h by Day 14 CL of the estrous cycle or at 8
      h by Day 200 CL of pregnancy but trichosanthin at 100 ng/mL did not affect (p >
      or = 0.05) secretion of progesterone in vitro by Day 14 CL of the estrous cycle
      or Day 200 CL of pregnancy at 4 or 8 h. Pregnancy specific protein B (PSPB)
      increased (p < or = 0.05) secretion of progesterone in vitro at 4 and 8 h by Day
      14 CL of the estrous cycle and did not differ between incubation times (p > or =
      0.05). PSPB increased secretion of progesterone at 4 h but not at 8 h (p > or =
      0.05) by Day 200 CL of pregnancy. These data suggest that PGE2 or PSPB but not
      LH, 8-Epi-PGE1 or 8-Epi-PGE2 regulates luteal secretion of progesterone by bovine
      CL at mid-pregnancy. In addition, it is suggested that weights of bovine CL of
      pregnancy increase to compensate for a lack of placental secretion of
      progesterone.

PMID- 9661217
TI  - Involvement of prostaglandins produced by cyclooxygenase-1 in murine
      visceronociception induced by phenylquinone.
AB  - Intraperitoneal injection of phenyl-p-benzoquinone (phenylquinone, PQ) induced
      writhing in mice for up to 30 min. During this time, the peritoneal content of 6
      keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), a stable degradation product of
      PG12, was highest in the 15-min. sample. In the peritoneal cells, the mRNA
      expression for the constitutive cyclooxygenase-1 (COX-1) was unchanged by PQ
      administration. In contrast, little mRNA for COX-2 was detected in the peritoneal
      cells from unstimulated animals, and was induced 60-120 min. after PQ
      administration. PGs involved in the induction of writhing thus seem to be derived
      from a COX-1 reaction. Oral administration of mofezolac, a non-steroidal anti
      inflammatory drug which potently inhibits COX-1, suppressed the PQ-induced
      writhing and peritoneal accumulation of PGs without affecting mRNA expression for
      both COX isoforms in mice.

PMID- 9661218
TI  - Iloprost added to the cardioplegic solutions improves myocardial performance.
AB  - A total of 12 mongrel dogs were divided into two equal groups. Six animals
      received IIoprost and the other 6 animals did not receive any additional
      treatment. In the Iloprost group, Iloprost was added to the cardioplegic solution
      (25 ng). Also, Iloprost was used (10 ng/kg/min.) 5 min. before and after cross
      clamping. All cardiac output and biochemical measurements were evaluated before
      cross-clamp and 15 min., 1 h, and 4 h after cross-clamp. The measured dp/dt shows
      that the hearts treated with Iloprost preserved left ventricular function.
      Comparison of contractility indices between the groups revealed that contractile
      recovery was 59% in the control group and 71% in the Iloprost group (p < 0.05).
      Tumor necrosis factor (TNF) alpha level was significantly elevated in the control
      group (p < 0.001). Its level was 22.2 +/- 2.2 pg/mL in the control group and 13.8
      +/- 1.0 pg/mL in the Iloprost group. E- and P-selectin levels were elevated in
      the control group (p < 0.001). ICAM-1 level was also elevated in the control
      group. ICAM-1 level was 17.7 +/- 1.8 ng/mL in the control group and 8.5 +/- 1.8
      ng/mL in the Iloprost group. The Iloprost that was added to the cardioplegic
      solution and low dose administration during the pre- and post-ischemic period
      inhibits the toxic mediator release from endothelium-leukocyte interaction and
      reduces the severity of ischemia-reperfusion injury.

PMID- 9661219
TI  - Do E-series prostaglandins and their metabolites influence oxidation of native
      and glycated low-density lipoproteins?
AB  - Oxidation of lipoproteins, and, in particular, low-density lipoproteins (LDL),
      has been shown to play a significant role in the pathogenesis of atherosclerosis.
      Oxidized LDL are endocytosed via scavenger receptors to form lipid-laden foam
      cells. The non-enzymatic reaction of glucose with proteins and lipoproteins
      results in a modified LDL involved in the pathogenesis of late complications in
      diabetes mellitus. In the present paper, the influence of various E-series
      prostaglandins (PGE1; 13,14-dihydro PGE1; 13,14-dihydro 15-keto PGE1; and PGE2)
      on oxidation of native and glycated LDL was investigated. The effect of these
      agents in the concentration range from 1 pg/mL to 1.6 micrograms/mL on copper
      induced oxidation of native and glycated LDL was tested. The concentration of
      each agent causing the maximal effect on oxidation of native LDL, as measured by
      the formation of thiobarbituric acid-reacting substances, was chosen to estimate
      the effect on 2, 4, 8, and 24 h oxidation of glycated LDL. The study was
      performed with LDL isolated by sequential ultracentrifugation from normolipidemic
      individuals. LDL (0.25 mg protein/mL) was oxidatively modified with 5 microM
      CuSO4. The glycosylation of LDL was performed by incubation of LDL with 500 mM
      glucose for varying periods of time ranging from 10 to 31 days. Our results show
      that only 13,14-dihydro PGE1 significantly inhibits copper-induced oxidation of
      native LDL, while the other examined E-series prostaglandins in vitro are
      ineffective as reducing agents in LDL-oxidation.

PMID- 9661220
TI  - Confronting violence. Committee on Psychopathology of the Group for the
      Advancement of Psychiatry.

PMID- 9661221
TI  - Discrimination in psychiatric disability coverage and the Americans With
      Disabilities Act.

PMID- 9661222
TI  - What our students teach us about managing care ethically.

PMID- 9661223
TI  - Treatment for all: the computer as a patient assistant.

PMID- 9661224
TI  - Predicting rehabilitation outcome among patients with schizophrenia.

PMID- 9661225
TI  - Linking inpatients with schizophrenia to outpatient care.
AB  - OBJECTIVE: This study focused on inpatients with schizophrenia or schizoaffective
      disorder who were scheduled to begin outpatient care with clinicians who had not
      previously treated them. The authors evaluated the effects of communication
      between the patients and their outpatient clinicians before discharge on
      patients' referral compliance, psychiatric symptoms, and community function at
      follow-up three months after discharge. METHODS: A total of 104 adult inpatients
      with schizophrenia or schizoaffective disorder who were scheduled to receive
      outpatient care from clinicians who had not previously treated them were
      evaluated at hospital discharge and again three months later. Comparisons were
      made between patients who had telephone or face-to-face contact with an
      outpatient clinician before hospital discharge and patients who did not have such
      contact. RESULTS: About half (51 percent) of the inpatient sample communicated
      with an outpatient clinician before leaving the hospital. Compared with patients
      who had no communication, those who spoke with an outpatient clinician were
      significantly more likely to complete the outpatient referral. After baseline
      scores and other covariates were controlled for, predischarge contact with an
      outpatient clinician was associated with a significantly lower total Brief
      Psychiatric Rating Scale score at follow-up and less self-assessed difficulty
      controlling symptoms. Nonsignificant trends toward improved medication compliance
      and a lower rate of homelessness were also found. The two patients groups did not
      significantly differ in the proportion who were readmitted to the hospital or who
      made a psychiatric emergency room visit during the follow-up period. CONCLUSIONS:
      Direct communication between inpatients and new outpatient clinicians may help
      smooth the transition to outpatient care and thereby contribute to improved
      control of clinical symptoms.

PMID- 9661226
TI  - Family caregivers' criticism of patients with schizophrenia.
AB  - OBJECTIVE: Relationships were examined between patients' negative symptoms,
      family caregivers' knowledge of schizophrenia, caregivers' attributions about the
      cause of patients' symptoms, and caregivers' response to the symptoms. METHODS: A
      sample of 84 caregivers of patients with schizophrenia in Brisbane, Australia,
      were interviewed using a structured format and measures designed for the study.
      RESULTS: Results of regression analyses indicated that three variables
      significantly predicted caregivers' criticism of patients--a smaller proportion
      of negative symptoms in the patient's overall symptom pattern, the caregiver's
      low level of knowledge about the illness, and the caregiver's attributing the
      cause of negative symptoms to the patient's personality rather than to the
      illness. CONCLUSIONS: Overall, findings supported the utility of an attributional
      framework in enhancing conceptions about and research on schizophrenia and family
      caregiving.

PMID- 9661227
TI  - Group treatment for smoking cessation among persons with schizophrenia.
AB  - People with schizophrenia smoke more than the general population and more than
      other psychiatric diagnostic groups. The rate of smoking in the general
      population is 30 percent, and reported rates for people with schizophrenia range
      between 62 percent and 81 percent. The author briefly reviews evidence that
      nicotine's augmentation of dopamine release may account for the high prevalence
      of smoking in this group. The affective, cognitive, and social difficulties and
      the symptoms experienced by many patients with schizophrenia indicate that
      existing smoking cessation programs may not be appropriate for them. The author
      describes three programs developed for use with this population and reviews
      evidence of their effectiveness. Preliminary evidence suggests that transdermal
      nicotine patches are effective and that patients do not misuse them. The author
      concludes that stopping smoking is possible for individuals with schizophrenia,
      especially if the treatment is specifically designed for them.

PMID- 9661228
TI  - Customer satisfaction and self-reported treatment outcomes among psychiatric
      inpatients.
AB  - OBJECTIVE: Relationships among different dimensions of patient satisfaction and
      selected demographic, clinical, and outcome variables were explored in a sample
      of severely ill people receiving inpatient psychiatric services. METHOD: The
      sample consisted of 81 patients admitted to and discharged from an inpatient
      psychiatric unit at a midwestern Veterans Affairs medical center. Stepwise
      multiple regression was used to examine the relationship between patient
      satisfaction and self-reported changes in quality of life, symptomatology, and
      level of functioning as measured by the Treatment Outcome Profile. Other
      variables such as diagnosis, length of stay, employment, living situation, and
      prior psychiatric and substance abuse treatment were also considered. A subsample
      of the most satisfied and dissatisfied patients was chosen to further explore
      variables contributing to satisfaction with services. RESULTS: Patient
      satisfaction was related to initial level of functioning, certain diagnoses, and
      treatment gains. Clinicians were highly accurate in identifying patients who were
      satisfied, based on blind chart reviews. CONCLUSIONS: This study underscores the
      significant relationships between patient satisfaction, psychiatric diagnosis,
      and other outcome measures, and argues for the validity and utility of patient
      satisfaction measures in assessing the efficacy of inpatient care.

PMID- 9661229
TI  - Relationship of cocaine and other substance dependence to well-being of high-risk
      psychiatric patients.
AB  - OBJECTIVE: The co-occurrence of substance dependence disorders was determined in
      a sample of 160 frequently hospitalized adults with severe mental illness, and
      the relationship between substance dependence and psychosocial functioning and
      well-being was examined. METHODS: A structured interview was used to assess
      subjects for co-occurring current DSM-III-R substance dependence disorders during
      an acute psychiatric hospitalization. They were administered a structed interview
      that included the subscales of the Addiction Severity Index, the Center for
      Epidemiological Studies-Depression Scale, Lehman's Quality of Life Interview,
      Rosenberg's Self-Esteem Scale, the Mastery Scale, and questions about service
      needs. RESULTS: Seventy-eight of the subjects (48.8 percent) were diagnosed as
      having at least one current substance dependence disorder. Most subjects with
      comorbid substance dependence were polysubstance dependent (55.1 percent), and
      almost half (44.9 percent) met criteria for cocaine dependence. Subjects who were
      substance dependent were significantly overrepresented among those diagnosed with
      bipolar disorder, psychotic disorder not otherwise specified, and major
      depression. When the analysis controlled for demographic characteristics and
      primary diagnosis, comorbidity was related to depressive symptoms, adverse life
      conditions, and diminished life satisfaction in several domains. Substance
      dependent subjects were significantly more likely to have been arrested and
      jailed than nondependent subjects. Cocaine-dependent subjects were significantly
      less satisfied than all other subjects with their living situation and personal
      safety and more likely to request assistance for their drug and alcohol use
      problems. CONCLUSIONS: The findings corroborate high rates of co-occurring
      substance dependence disorders among frequently hospitalized patients with severe
      mental illness. They also reveal a high prevalence of cocaine dependence and a
      dramatic pattern of negative correlates of cocaine dependence. The findings
      suggest that successful interventions for substance dependence may improve these
      patients' life circumstances and that psychiatric patients may be particularly
      receptive to such interventions during hospitalization.

PMID- 9661230
TI  - Clinicians' decision making about involuntary commitment.
AB  - OBJECTIVE: Clinicians' decision making about involuntary commitment was examined,
      with a focus on the effects of patient and clinician characteristics and bed
      availability on decisions to detain patients, the first step in involuntary
      commitment. METHODS: Eighteen psychologists and social workers in the emergency
      service of a community mental health center completed the Risk Assessment
      Questionnaire for 169 consecutive patients they deemed to present some degree of
      risk. Forty-two patients were detained. RESULTS: Three underlying constructs were
      significantly associated with a patient's overall risk rating, which in turn
      predicted the decision to detain. Two were clinician characteristics: the
      clinician detention ratio, which reflects the proportion of patients detained by
      the clinician in the past three months, and the setting in which the evaluation
      occurred, either an in-house emergency service or a mobile crisis unit. The
      availability of detention beds in the community was also a significant predictor
      of whether a patient would be detained. No patient characteristic, including
      diagnosis, sex, age, or insurance status, was significantly related to the
      detention decision. CONCLUSIONS: The findings suggest that the decision-making
      process is influenced by multiple factors, such as setting, the clinician's
      tendency to detain patients, and the availability of detention beds.

PMID- 9661231
TI  - Comparative outcomes and costs of inpatient care and supportive housing for
      substance-dependent veterans.
AB  - OBJECTIVE: This study examined the differential effectiveness and costs of three
      weeks of treatment for patients with moderately severe substance dependence
      assigned to inpatient treatment or to a supportive housing setting. Supportive
      housing is temporary housing that allows a patient to participate in an intensive
      hospital-based treatment program. Type and intensity of treatment were generally
      equivalent for the two groups. METHODS: Patients were consecutive voluntary
      admissions to the substance abuse treatment program of a large metropolitan
      Veterans Affairs medical center. Patients with serious medical conditions or
      highly unstable psychiatric disorders were excluded. Patients in supportive
      housing attended the inpatient program on weekdays from 7:30 a.m. to 5 p.m. They
      were assessed at baseline and at two-month follow-up. RESULTS: Baseline analyses
      of clinical, personality, and demographic characteristics revealed no substantive
      differences between the 62 patients assigned to inpatient treatment and the 36
      assigned to supportive housing. The degree of treatment involvement and dropout
      rates did not differ between groups. Of the 55 inpatients completing treatment,
      29 were known to be abstinent at follow-up, and of the 35 supportive housing
      patients completing treatment, 22 were abstinent. The proportion was similar for
      both groups, about 70 percent. The cost of a successful treatment for the
      inpatient group was $9,524. For the supportive housing group, it was $4,291.
      CONCLUSIONS: Given the absence of differential treatment effects between
      inpatient and supportive housing settings, the use of supportive housing
      alternatives appears to provide an opportunity for substantial cost savings for
      VA patients with substance dependence disorders.

PMID- 9661232
TI  - Functional impairment associated with psychological distress and medical severity
      in rural primary care patients.
AB  - OBJECTIVE: The study examined functional impairment associated with psychological
      distress and severity of medical illness in a rural primary care population and
      explored how functional impairment varied with psychological distress and chronic
      medical illness. METHODS: Fifty-eight patients recruited from three rural primary
      care clinics completed the 36-item Short Form Health Survey (SF-36) and the
      Typology of Psychic Distress (PsyDis). The chronic disease score, a measure of
      the severity of chronic medical illness, was calculated from data on use of
      prescription medications over a six-month period. T tests were used to determine
      the level of functional impairment associated with various levels of
      psychological distress and medical illness. Regression analyses were used to
      determine the proportion of variance in impairment that was explained by level of
      psychological distress and severity of medical illness. RESULTS: High levels of
      psychological distress explained the variance in impairment in several domains
      measured by the SF-36, including general health, social functioning, emotional
      role, and mental health, whereas a high level of severity of chronic medical
      illness explained the variance in impairment in physical functioning. Both high
      psychological distress and high severity of chronic medical illness explained the
      variance in impairment in vitality, and neither variable explained variance in
      impairment in physical role or bodily pain. CONCLUSIONS: In this rural outpatient
      primary care population, functional impairment was explained more by
      psychological distress than by severity of medical illness. Decreasing the burden
      of psychological distress among primary care patients may improve functioning.

PMID- 9661233
TI  - Analysis of health service areas: another piece of the psychiatric workforce
      puzzle.
AB  - Planning for development of a national or regional psychiatrist workforce that is
      the appropriate size must consider numerous issues. They include the dynamics of
      workforce distribution, effects of managed care, reduction in potential residency
      slots, participation of international medical graduates, apathy toward the field
      of psychiatry, service area variations, and increased interest in allied mental
      health professions, along with the burgeoning global burden of psychiatric
      illness. This paper examines the application of two benchmark standards for the
      number of psychiatrists needed per 100,000 population--the standard developed by
      the Graduate Medical Education National Advisory Committee and the Average
      Requirement Benchmark--to the supply of psychiatrists in Georgia in 1996 by
      county and by health service regions, which are geographical units based on
      health care utilization patterns of Medicare and Medicaid recipients. Areas with
      a surplus or deficit of psychiatrists are identified. The findings provide
      contextual evidence of a surplus of psychiatric physicians in the most populous
      areas of the state, given a substantial presence of health maintenance
      organizations. The state's less populated rural areas may potentially benefit
      from a redistribution of the psychiatrist workforce. The authors recommend
      continued refinement of models to estimate psychiatric workforce needs and
      suggest development of a comprehensive model that uses needs-based, demand-based,
      and benchmarking approaches.

PMID- 9661234
TI  - Impact of Medicaid managed mental health care on delivery of services in a rural
      state: an AMI perspective.
AB  - In March 1995 Iowa implemented a statewide mental health carve-out program under
      a Medicaid Section 1915b waiver. A goal was to provide equal access across
      counties for Medicaid recipients by introducing a statewide network of service
      providers. Problems have included the contractor's authorizing only services
      considered medically necessary for persons with serious mental illness, who also
      need community supports; contractor staff's lack of knowledge about regional
      resources and the limited availability of community-based services in most rural
      areas; clients' difficulty in gaining access to the new system; denial of
      inpatient hospitalization; untimely provider payments; and lack of education for
      providers, consumers, and families.

PMID- 9661235
TI  - Rural telepsychiatry.
AB  - Telepsychiatry is the use of telecommunications technology to connect patients
      and health care providers, permitting effective diagnosis, education, treatment,
      consultation, transfer of medical data, research, and other health care
      activities. Telepsychiatry has been used as a partial solution to the problem of
      limited psychiatric services for clinics and hospitals in remote areas of areas
      underserved by psychiatrists and other mental health care specialists. In the
      United States, eastern Oregon's RodeoNet telepsychiatry program and the
      telemedicine program of the Kansas University Medical Center, which has a
      psychiatric component, are excellent models. Telepsychiatric applications can be
      cost-effective, but careful evaluation is needed.

PMID- 9661236
TI  - Linking primary care and rural psychiatry: where have we been and where are we
      going?
AB  - Linking primary care with psychiatric care has long been promoted as a way to
      improve access to rural mental health services. The authors describe a national
      survey that identified 53 successfully linked programs, ranging from small local
      efforts to sophisticated multicounty networks. Findings indicated that lessons
      from successful integrations are not easily reduced to a how-to list.
      Organizations cooperate with each other when it is in their interests to do so.
      Motivation to integrate cannot be mandated, nor is the availability of funding
      alone sufficient to provide motivation. The authors discuss ways that managed
      care may facilitate or hinder the link between rural primary care and rural
      psychiatry.

PMID- 9661237
TI  - Rural psychiatry in developing countries.
AB  - During the last two decades several initiatives have been taken to improve
      psychiatric services in low-income rural areas in developing countries. They have
      included the formulation of national mental health programs and establishment of
      pilot programs for integration of mental health care with primary health care in
      India, Iran, and other countries in Asia, Africa, and South America. The
      psychiatrist has multiple roles to play in meeting the many challenges of
      providing mental health care in rural areas in developing countries.

PMID- 9661238
TI  - Depression among pregnant adolescents.

PMID- 9661239
TI  - Assaults on staff.

PMID- 9661240
TI  - Employer expenditures for behavioral health benefits dropped 54 percent in the
      past decade, study shows.

PMID- 9661241
TI  - Report describes epidemic of alcohol abuse and misuse of prescription drugs by
      older Americans.

PMID- 9661242
TI  - Orthopedic management of neuromuscular disorders in children.
AB  - In many cases, the orthopedic surgeon may be the first consultant requested to
      assess complaints of lower extremity weakness or deformity to result from such
      conditions and must remain alert to the primary diagnosis. In addition, the
      orthopedic surgeon should be prepared to guide appropriate physical therapy,
      prescribe orthotics, and perform surgery to improve function, prevent deformity,
      or provide comfort when necessary. Most deformities of the extremities result
      from a combination of muscle weakness and imbalance, and surgical procedures are
      aimed at correcting existing deformity and rebalancing existing musculature by
      release or transfer. Skeletally immature patients with neuromuscular disorders
      are also susceptible to the development of scoliosis, which may impair
      comfortable sitting or already compromised pulmonary function. This article
      reviews the clinical manifestation and orthopedic management of Duchenne's
      muscular dystrophy, spinal muscular atrophy, facioscapulohumeral dystrophy, and
      Charcot-Marie-Tooth disease.

PMID- 9661243
TI  - The management of neuromuscular ventilatory failure.
AB  - All patients with respiratory impairment have either primarily ventilatory or
      primarily oxygenation impairment. Patients with neuromuscular conditions fall
      into the former category but are all too often managed as though they had the
      latter with oxygen therapy, bronchodilators, chest physical therapy, intermittent
      positive pressure breathing, and so on. This approach can only hasten respiratory
      failure and management by tracheostomy-However, it has been reported that with
      the use of noninvasive respiratory muscle aids, respiratory morbidity and
      mortality can be prevented for most patients with neuromuscular disease without
      resort to tracheostomy or even hospitalization.

PMID- 9661244
TI  - Nutrition and swallowing in pediatric neuromuscular patients.
AB  - The management of the patient with neuromuscular disease is complex. Every child
      should be seen as a distinct individual and therefore merits patient-specific
      assessment and intervention. This article reviews nutritional management using
      spinal muscular atrophy and Duchenne's muscular dystrophy as representative
      models. The history of nutritional intake, nutritional needs, and underlying
      medical problems with physical examination, anthropometric, body composition, and
      biochemical markers are all important parts of the assessment and should be done
      at regular intervals. Intervention may include calorie restriction or calorie
      supplementation. Treatment strategies that follow diagnosis of dysphagia include
      positioning, increased sensory input, or direct maneuvers, such as volume changes
      or thickening liquid. Percutaneous endoscopic gastrostomy can be safely placed in
      almost all situations with minimal risk. Patients benefit most from a
      multidisciplinary and systematic management program.

PMID- 9661245
TI  - The psychosocial and cognitive impact of Duchenne's muscular dystrophy.
AB  - Duchenne's muscular dystrophy (DMD) is the most prevalent and devastating of
      neuromuscular disorders. Children given this diagnosis not only face inevitable
      deterioration of physical functioning, but they also become susceptible to
      emotional/behavioral problems, as well as reduced cognitive functioning and
      learning problems. This article (1) reviews the emotional/behavioral issues that
      may impact the child with DMD and the affected child's family members and
      caregivers; (2) examines the research describing the cognitive and learning
      issues associated with DMD; (3) provides recommendations for physicians who work
      with these families; and (4) recommends directions for future research that will
      help to further elucidate emotional/behavioral issues and cognitive and learning
      correlates of DMD.

PMID- 9661246
TI  - Bioethics in pediatric neuromuscular disease.
AB  - The increasing frequency with which bioethical issues arise in the medical care
      of pediatric patients with neuromuscular disease suggests a need for a working
      knowledge of the field for the clinical physician, Institutional Bioethics
      Committees are multidisciplinary groups that include medical, nursing, social
      service, legal, religious or chaplaincy, and community representation. The role
      and functioning of these committees vary widely according to institution.
      Inherent in the process of consent is that it must be an Informed consent. This
      requires that the person consenting has been given adequate information to
      understand and to appreciate the benefits and risks of the treatment. There are
      some instances in which consent by minor patients is necessary.

PMID- 9661247
TI  - CART peptides in the central control of feeding and interactions with
      neuropeptide Y.
AB  - While CART peptides have been implicated as novel, putative peptide
      neurotransmitters/cotransmitters, behavioral effects of these peptides have not
      yet been demonstrated. In this study, we show the first behavioral effect of CART
      peptides. I.c.v. administration of CART peptide fragments inhibits feeding in
      rats. Moreover, injection of an antibody to CART peptide 82-103 stimulates
      feeding, suggesting that endogenous CART peptides exert an inhibitory tone on
      feeding. Injection of CART peptide 82-103 five min before NPY reduces the
      increase in feeding caused by injection of NPY alone. Also, in light microscopic
      immunohistochemical studies, NPY-positive varicosities were observed around CART
      peptide-positive cell bodies in the paraventricular nucleus of the hypothalamus.
      These data suggest functional interactions between CART peptides and NPY. These
      results indicate that CART peptides play a role in the control of food intake by
      the brain.

PMID- 9661248
TI  - Amygdala-kindling induces a lasting reduction of GABA-immunoreactive neurons in a
      discrete area of the ipsilateral piriform cortex.
AB  - Several lines of evidence indicate a critical role of the piriform cortex (PC) in
      the kindling model of temporal lobe epilepsy, suggesting that the PC is part of
      an epileptic network that is pivotal in the genesis of kindling, facilitating,
      and intensifying the spread of seizures from a focus in amygdala, hippocampus, or
      other limbic brain regions to cortical and subcortical regions. Kindling of the
      amygdala has been shown to induce long-lasting changes in synaptic efficacy in
      the ipsilateral PC comparable to abnormalities seen in epileptic foci, but the
      neurochemical alterations possibly underlying these functional changes are not
      known. The possibility that the enhanced excitability of the PC in response to
      kindling is related to a reduction of GABAergic neurotransmission prompted us to
      examine if a lasting reduction in GABA-immunoreactive PC neurons is detectable
      after kindling of the basolateral amygdala (BLA) in rats. Furthermore, GABA
      immunoreactivity was determined in the BLA in order to investigate whether
      GABAergic neurons decrease in focal tissue, as previously suggested by
      neurochemical and immunocytochemical studies in amygdala-kindled rats. Three
      groups of age-matched rats were used: (1) a group of rats that was kindled via
      electrical stimulation by a bipolar electrode implanted in the right BLA, (2) a
      group of BLA-implanted but nonstimulated rats, and (3) a group of non-implanted,
      naive control rats. The kindled rats were sacrificed 40 days after the last fully
      kindled seizure. The two other groups of rats were sacrificed together with the
      kindled rats on the same days, and tissues from kindled and control rats were
      treated concurrently throughout the immunohistochemical analysis. GABA neurons
      were stained by a monoclonal antibody to GABA. Kindling of the BLA led to a
      pronounced decrease in the number of GABA immunoreactive neurons in the ipsi- and
      contralateral BLA at all section levels examined. In the PC, no significant
      differences between groups were seen in the contralateral hemisphere, while a
      significant reduction in GABA immunoreactive cells was observed in the transition
      zone between anterior and posterior PC in the hemisphere ipsilateral to the BLA
      electrode. The present findings add to the accumulating evidence that the PC is
      critically involved in kindling-induced epileptogenesis. The data furthermore
      substantiate that the PC is not a homogeneous structure but that there are
      differences along the anterior-posterior axis of this region in neurochemical
      (and most certainly also functional) consequences in response to kindling
      stimulation from other limbic brain regions.

PMID- 9661249
TI  - Amphetamine-induced neurochemical and locomotor responses are expressed
      differentially across the anteroposterior axis of the core and shell
      subterritories of the nucleus accumbens.
AB  - The administration of psychostimulants increases dopamine (DA) release within the
      nucleus accumbens (NAC), a terminal projection site of mesolimbic DA neurons,
      originating in the ventral tegmental area (VTA). Recent evidence demonstrates
      that two subdivisions of the NAC, the dorsolateral core and the ventromedial
      shell, can be distinguished by morphological and immunohistochemical differences,
      as well as by their distinct anatomical connections. It has been suggested that
      these two subregions subserve different functions that are related to goal
      directed behaviors, stimulus-reward associations, and reinforcement induced by
      addictive drugs. The shell region, in particular, modulates inputs from the
      limbic system, whereas the core is preferentially innervated by nuclei that
      process motor information. In the present study, we sought to investigate if (1)
      the direct infusion of d-amphetamine (AMPH) by reverse microdialysis into either
      the core or shell of the NAC across its anteroposterior axis differentially
      affects dialysate DA and 5-HT levels, and (2) these subterritories also subserve
      different behavioral functions. Following the determination of basal DA and 5-HT
      levels, four increasing concentrations of AMPH (0.05, 0.10, 0.50, 1.00 microM)
      were substituted for the dialysis perfusate for 60 min each. Movement units were
      detected by an infrared sensor and were transmitted through a motion interface to
      an activity monitor analyzer. AMPH produced a dose-dependent increase in
      locomotor activity after microinfusion into either the rostral shell, caudal
      shell or core of the NAC. The potency of the AMPH-induced locomotor activating
      effect was significantly higher in the rostral shell of the NAC compared with the
      caudal shell and the core. The lowest concentrations of AMPH (0.05, 0.1 microM)
      produced an equipotent decrease in dialysate DA in either the rostral shell,
      caudal shell, or core. At 1.0 microM, however, AMPH selectively increased DA in
      the rostral shell, whereas DA reached baseline values both in the caudal shell
      and core. Basal dialysate DA levels were significantly higher in the core
      relative to both the rostral and caudal parts of the shell. The highest dose of
      AMPH significantly increased dialysate 5-HT levels over baseline only in the
      caudal shell of the NAC. The basal dialysate 5-HT levels did not significantly
      differ between the three subterritories of the NAC. These results emphasize the
      heterogeneity and functional compartmentalization within the NAC, the
      differential regulation of neurochemical and motor responses across the
      anteroposterior axis of the NAC, and the preferential effect of AMPH in the
      rostral shell subterritory of the NAC.

PMID- 9661250
TI  - Distribution of glutamate decarboxylase65 immunoreactive puncta on pyramidal and
      nonpyramidal neurons in hippocampus of schizophrenic brain.
AB  - Recent studies have reported an increase in GABAA receptor binding activity in
      several key corticolimbic regions, including the hippocampal formation, of
      postmortem schizophrenic brain. Because this change has been postulated to
      represent a compensatory upregulation of this receptor, the current report has
      sought to determine whether a decrease of glutamate decarboxylase (GAD), the
      enzyme responsible for the synthesis of GABA, may also be present in the
      hippocampus of schizophrenic subjects. A standard immunoperoxidase technique,
      together with a computer-assisted microscopic analysis, has been employed to
      evaluate the distribution of the 65 kDalton isoform of GAD (GAD65) in 12 normal
      controls and 13 schizophrenic subjects matched for age and postmortem interval
      (PMI). The results show no significant difference in the density of GAD65
      immunoreactive (-IR) puncta in contact with pyramidal neurons (PN), nonpyramidal
      neurons (NP), or neuropil (NPL) in sectors CA1-4 and their various sub-laminae.
      When the data were considered in relation to neuroleptic exposure, a significant
      positive correlation between the density of GAD65-IR puncta and drug dose was
      found on both PNs (r = 0.814, P = 0.002; r = 0.777, P = 0.005, respectively) and
      NPs (r = 0.673, P = 0.023; r = 0.672, P = 0.024, respectively) in sectors CA4 and
      CA3. A similar result was found in the stratum oriens of CA3 (r = 0.704, P =
      0.016) and CA2 (r = 0.774, P = 0.009). In each instance, two neuroleptic free
      schizophrenics showed the lowest density of GAD65-IR puncta. There was no
      significant relationship between the density of GAD65-IR puncta with either age
      or PMI. Taken together with previous data showing an upregulation of GABAA
      receptor activity in sectors CA3 and CA2, particularly the stratum oriens, this
      study provides further evidence in support of the hypothesis that an intrinsic
      defect of GABAergic activity may occur in the hippocampal formation of
      schizophrenic patients and show dose-related increases in relation to neuroleptic
      exposure.

PMID- 9661251
TI  - Trimethyltin intoxication induces marked changes in neuropeptide expression in
      the rat hippocampus.
AB  - In situ hybridization and immunocytochemistry were applied to investigate changes
      in the expression of somatostatin, neuropeptide Y, neurokinin B, cholecystokinin,
      dynorphin, and Met-enkephalin in the rat hippocampus after administration of a
      single peroral dose of trimethyltin hydroxide (9 mg/kg). Two time intervals were
      investigated: 5 days after trimethyltin treatment, when CA3 damage becomes
      manifest and is associated with increased aggression, seizure susceptibility, and
      memory deficit, and 16 days after trimethyltin, when neuronal damage is almost
      maximal and seizure susceptibility is declining. Robust but transient increases
      of neuropeptide Y, neurokinin B, and Met-enkephalin mRNA levels were revealed in
      the granule cell layer of the dentate gyrus and increased neuropeptide Y and
      neurokinin B immunoreactivities were found in mossy fibers. In reverse, dynorphin
      mRNA and immunoreactivity were decreased transiently in the dentate gyrus and
      mossy fibers, respectively. Strong over-expression of NPY mRNA was also observed
      in hilar interneurons and in CA1 and CA3 pyramidal cells as well as in the cortex
      at 5 days postdosing. Cholecystokinin- or neurokinin B-containing basket cells
      were preserved, while somatostatin-bearing interneurons were damaged by
      trimethyltin exposure. These neurochemical changes induced by trimethyltin
      intoxication strikingly parallel to those observed in animal models of temporal
      lobe epilepsy and may reflect activation of endogenous protective mechanisms. It
      is also suggested that hilar interneurons respond differently to trimethyltin
      exposure, for which neuropeptides are valuable markers.

PMID- 9661252
TI  - Inducibility of c-Fos protein in visuo-motor system and limbic structures after
      acute and repeated administration of nicotine in the rat.
AB  - To identify neuroanatomical substrates affected by nicotine, we have studied its
      effects after acute and repeated administration through the c-Fos protein
      inducibility in various brain structures. Ninety minutes after acute nicotine
      (0.35 mg/kg, s.c.) the number of c-Fos-like immunoreactive nuclei was
      consistently increased in visuo-motor structures such as the superior colliculus,
      the medial terminal nucleus of accessory optic tract, and the nucleus of the
      optic tract. The anteroventral and lateroposterior thalamic nuclei, connected
      with the retina and involved in limbic processing, showed a c-Fos induction. c
      Fos was preferentially induced in terminal fields of neurons of the ventral
      tegmental area such as the nucleus accumbens, the central amygdala, the lateral
      habenula, the lateral septum, as well as the cingulate, medial prefrontal,
      orbital and piriform cortices. In chronically treated rats (0.35 mg/kg s.c., 3 x
      day for 14 days), the last nicotine injection given on the 15th day was still
      able to induce 90 minutes later c-Fos protein in visuo-motor, retino-limbic,
      subcortical, and cortical limbic structures. Moreover, this chronic treatment
      produced an additional recruitment of c-Fos-positive nuclei in the cingulate
      cortex, the core and the ventral shell of the nucleus accumbens. c-Fos induction
      after nicotine differs from that reported after other addictive drugs in terms of
      pattern and chronic inducibility, indicating that different mechanisms are
      involved for maintaining this transcription factor. In addition to a preferential
      sensitivity of mesolimbic dopaminergic neurons to nicotine, activation of visuo
      limbic and limbic regions could be relevant for understanding some context
      dependent and addictive behaviors produced by nicotine.

PMID- 9661253
TI  - Lamotrigine inhibits depolarization-evoked Ca++ influx in dissociated amygdala
      neurons.
AB  - Spectrophotometry with the Ca(++)-sensitive dye fura-2 was used to study the
      effect of lamotrigine (LAG) on the depolarization-evoked Ca++ influx in the
      acutely isolated basolateral amygdala neurons. Depolarization of the neurons with
      high K+ resulted in the elevation of intracellular Ca++ concentration [Ca++]i in
      a concentration-dependent manner. The K(+)-induced Ca++ influx was completely
      blocked in the Ca(++)-free solution or by Cd++, indicating that depolarization
      induced increases in [Ca++]i were triggered largely, if not at all, by Ca++ entry
      from extracellular space and Ca++ entry occurred through voltage-dependent Ca++
      channels. Application of LAG reduced the depolarization-evoked Ca++ influx in a
      concentration-dependent manner. The effect of LAG was markedly reduced in the
      presence of N-type Ca++ channel blocker omega-conotoxin-GVIA (omega-CgTX). These
      results suggest that the action of LAG is mediated, at least in part, by the
      modulation of N-type Ca++ channels.

PMID- 9661254
TI  - Prefrontal cortex-basal ganglia circuits in the rat: involvement of ventral
      pallidum and subthalamic nucleus.
AB  - The core of the nucleus accumbens (NAcc core) is the principal input structure to
      the basal ganglia circuitry for the prelimbic and medial orbital areas (PL/MO) of
      the prefrontal cortex. As is now well recognized in the rat, the main basal
      ganglia output of this prefrontal channel is the dorsomedial part of the
      substantia nigra pars reticulata (SNR) and not the ventral pallidum as previously
      suggested. There is evidence suggesting that the ventral pallidum is rather
      involved with the subthalamic nucleus (STN) in an indirect NAcc-SNR pathway.
      Indeed, we have recently shown that the NAcc core sends an inhibitory input to
      the lateral ventral pallidum (VPl), which projects to the medial STN. In the
      present study, we injected biocytin into the medial STN, at a site where neurons
      presented an inhibitory response to VPl stimulation. This produced anterogradely
      labelled fibres in the medial SNR and in the VPl. Furthermore, the stimulation of
      the VPl induced an inhibition in a majority of the STN cells identified, by the
      antidromic activation method, as projecting to SNR (76.6%) and/or back to the VPl
      (72.7%). In conclusion, these data further demonstrate the existence of an
      indirect striato-nigral pathway in the PL/MO channel and indicate that VPl is
      involved in an inhibitory feedback circuit, which modulates the discharge of
      medial STN. These results indicate that the medial STN is implicated in the
      limbic/cognitive functions of the basal ganglia.

PMID- 9661255
TI  - Effects of pentobarbital on the expression of GABAA receptor beta 1 mRNA in the
      hippocampus: differential responses of CA1 and CA3.
AB  - Effects of barbiturates have been linked to the inhibitory GABAA receptor in the
      brain. The present study examines changes in the expression of GABAA receptor in
      the hippocampus of pentobarbital treated rat. Intraperitoneal pentobarbital
      injections were administered once daily for 9 days at an increasing dose
      schedule, 30 mg/kg at day 1-3, 60 mg/kg day 4-6, and 90 mg/kg day 7-9. Within
      each of the three dosage periods, the duration of sleep and extent of reduction
      in body temperature of the rats decreased with time. Two hours after the 9th
      injection, 3H-muscimol binding of the hippocampal homogenates of the animals
      showed that the maximal number of binding sites (Bmax), 10.2 +/- 1.6 pmol/mg
      protein, was not significantly greater than 9.5 +/- 1.2 of saline control, but
      strikingly about 7-fold control level of beta 1 mRNA was seen in the pyramidal
      cells of CA1 and CA2, as revealed by in situ hybridization analysis with
      digoxigenin-cRNA probes. However, when the rats were withdrawn from pentobarbital
      injection for 24 hours and 7 days, the Bmax of the hippocampi was lowered to 7.3
      +/- 1.0 and 5.1 +/- 0.7, respectively, and the expression of beta 1 mRNA in CA1-2
      returned toward control. The pentobarbital treatment did not significantly alter
      the affinity of the radioligand to the receptor in the hippocampus and the
      expression of beta 1 mRNA in CA3 and CA4. The results suggest the plasticity of
      the beta 1 mRNA in CA1-2 as well as differential involvement of CA1-2 and CA3-4
      in response to the pentobarbital perturbation.

PMID- 9661256
TI  - Effects of estrogen agonists on amphetamine-stimulated striatal dopamine release.
AB  - Based upon the observation that estrogen acts in the striatum to rapidly modulate
      dopamine (DA) neural transmission and DA-mediated behaviors, it has been
      postulated that these effects of estrogen are mediated by a specific, membrane
      bound receptor mechanism. To further characterize the pharmacological specificity
      of the estrogen binding site, the present experiments examine effects of various
      estrogen agonists on amphetamine (AMPH)-induced DA release from striatal tissue
      of ovariectomized female rats, using a superfusion method. Catechol estrogens 4-,
      and 2-hydroxyestradiol, but not 2-methoxyestradiol, significantly enhance AMPH
      induced striatal DA release. Estrogen metabolites, estrone and estriol, and the
      non-steroidal estrogen analog, diethylstilbestrol, are without effects. Estradiol
      conjugated to bovine serum albumin (BSA) mimics the effect of estradiol to
      enhance stimulated striatal DA release. These results indicate that the steroidal
      configuration and hydroxylation on the A-ring of estrogenic compounds may be
      important determinants of ligand binding to the putative estrogen binding site in
      the striatum. Furthermore, the effectiveness of the estradiol conjugated to BSA
      reinforces the idea of an external membrane-bound receptor binding site in the
      striatum.

PMID- 9661257
TI  - In vivo electrophysiological assessment of the agonistic properties of
      flibanserin at pre- and postsynaptic 5-HT1A receptors in the rat brain.
AB  - Flibanserin (BIMT 17) has been described as a 5-HT1A agonist with preferential
      affinity for postsynaptic 5-HT1A receptors and as a 5-HT2A antagonist. Indeed,
      using the forskolin-stimulated cAMP accumulation technique, flibanserin but not
      the 5-HT1A agonists buspirone and 8-OH-DPAT had agonistic activity at
      postsynaptic 5-HT1A receptors in the cerebral cortex. The present in vivo
      electrophysiological study investigated the agonistic properties of this novel
      compound in pre- and postsynaptic areas of the anesthetized rat brain using local
      microiontophoretic application and systemic administration. The inhibition
      induced by either local or intravenous administration of flibanserin was current-
      and dose-dependent. Based on the ability of 5-HT1A antagonists to block or
      reverse the inhibitory action of the compound, the effect of flibanserin was
      shown to be mediated via 5-HT1A receptors. In addition, as determined by the
      concurrent microiontophoretic application of flibanserin and 5-HT, flibanserin
      behaved as a full agonist in the dorsal raphe nucleus (DRN) and the medial
      prefrontal cortex (mPFC), but as a partial agonist in the CA3 region of the
      hippocampus. Based on neuronal responsiveness observed with the local
      microiontophoretic application of flibanserin, it was found that the agonist was
      most potent on 5-HT1A receptors in the hippocampus, followed by the mPFC and DRN
      (I.T50 values: 260, 1,260, and 1,365 nanocoulombs, respectively). However, based
      on the ED50 values obtained from intravenous administration of the drug,
      flibanserin was most potent in the DRN followed by the hippocampus and mPFC (ED50
      values: 239, 1,414, and 2,984 micrograms/kg, respectively). Therefore,
      flibanserin presented a marked selectivity for postsynaptic 5-HT1A receptors when
      applied locally, but not when administered intravenously. It remains to be
      determined if flibanserin preferentially activates postsynaptic 5-HT1A receptors
      upon sustained systemic administration.

PMID- 9661258
TI  - GABAergic modulation of ventral pallidal dopamine release studied by in vivo
      microdialysis in the freely moving rat.
AB  - The mesopallidal dopamine system, which originates from the ventral tegmental
      area and projects to the ventral pallidum (VP), has been recently shown to play
      an important role in self-stimulation reward and cocaine reward. VP also receives
      a GABAergic projection from nucleus accumbens (NAS). The aim of the present study
      was to examine the involvement of this GABAergic projection in the modulation of
      VP dopamine release. Both the GABAA antagonist picrotoxin (2-200 microM) and the
      GABAB antagonist phaclofen (20-2,000 microM), perfused locally, dose-responsively
      increased VP extracellular dopamine 2-2.5-fold. Cocaine (10 microM) produced a
      6.5-fold increase of VP dopamine. Neither picrotoxin (200 microM), phaclofen
      (2,000 microM), nor GABA (20-2,000 microM) altered the response of VP dopamine to
      locally applied cocaine. GBR 12909 (0.5 microM), a selective dopamine uptake
      blocker, induced a 3.5-fold increase of VP dopamine. The increase of VP dopamine
      in response to GBR 12909 was further augmented to 8.5-fold of baseline when
      picrotoxin (200 microM) was added to the perfusate. The data from the present
      study demonstrate that the GABAergic NAS-VP projection can modulate ventral
      pallidal dopamine release. However, the effect of GABA on the mesopallidal
      dopamine system's response to locally applied cocaine may be complicated by
      actions of cocaine other than dopamine uptake inhibition.

PMID- 9661259
TI  - Fentanyl decreases beta-CIT binding to the dopamine transporter.
AB  - Evidence from animal studies suggest that centrally acting opiates increase
      synaptic dopamine (DA) concentration. However, the interaction between mu-opioid
      receptors and the DA system is unclear. We report here an effect of fentanyl on
      striatal [123I]beta-CIT binding to the DA transporter in a patient and in rats. A
      female patient underwent [123I]beta-CIT single-photon emission tomography (SPET)
      study after intrathecal injection of fentanyl for her back pain. After a 2-week
      drug-free period, the SPET study was repeated. In the experimental study, male
      Wistar rats were treated with fentanyl either acutely (50 micrograms/kg, i.p.)
      before imaging study or subacutely for 4 days (10 micrograms/kg, twice a day,
      i.p.). Brain planar imaging was performed at 3.5 hours after an intravenous
      injection of [123I]beta-CIT with gamma camera with a pinhole collimator. In a
      female patient, [123I]beta-CIT binding in the basal ganglia was decreased by 37%
      during fentanyl as compared to the binding after 2-week drug-free period.
      Similarly in rats, acute fentanyl treatment decreased [123I]beta-CIT binding to
      the striatum by 30% as compared to that of with the control rats. After subacute
      administration of fentanyl, no significant difference was observed compared to
      the control group. According to the present data, fentanyl decreases [123I]beta
      CIT binding in the basal ganglia both in human and rats, suggesting that opiates
      possibly directly affect DA reuptake.

PMID- 9661260
TI  - Expression of feline recombinant interferon-gamma in baculovirus and
      demonstration of biological activity.
AB  - We have previously reported the cloning of the coding sequence for feline
      specific interferon-gamma. Here, we describe the expression of this sequence in a
      baculovirus system and demonstrate the biological activity of the recombinant
      protein. The coding sequence for feline interferon was directionally cloned into
      the baculovirus transfer vector pAcCL29-1. Transfer vector and linearized wild
      type AcMNPV (BacPAK6) were used to co-transfect Sf9 cells by calcium phosphate
      coprecipitation. Subsequently, wild-type and recombinant viruses were separated
      by plaque assay. Recombinant plaques were expanded and a master stock of virus is
      produced. Production of biologically active interferon-gamma from infected Sf9
      cells was demonstrated using a standard cytopathic effect reduction assay,
      utilising vesicular stomatitis virus (VSV), and an MHC class II induction assay.

PMID- 9661261
TI  - Measurement of IgG, IgM and IgA concentrations in canine serum, saliva, tears and
      bile.
AB  - Capture ELISAs, for canine IgG, IgM, IgA and albumin, were developed and used to
      analyse immunoglobulin (Ig) concentrations in both serum and secretions. Matched
      samples of serum, saliva and tears were taken from 31 dogs, assigned to two
      groups based on age, whilst bile samples were obtained from nine adult dogs at
      post-mortem. Serum and tear IgA concentrations were significantly lower in dogs <
      or = 12 months of age compared with dogs > 12 months of age (p = 0.006 and 0.045,
      respectively). There was no significant correlation between serum and secretory
      Ig levels, with the single exception of serum and tear IgM concentrations (rp =
      0.553, p = 0.004). IgG and IgM concentrations were significantly correlated in
      matched tear and saliva samples (IgG: rp = 0.470, p = 0.023; IgM: rp = 0.651, p <
      0.0001). Albumin concentrations were significantly correlated with IgG, but not
      IgM or IgA, in both saliva and tears (saliva, rp = 0.581, p = 0.004; tears, rp =
      0.843, p < 0.0001) whilst IgA and IgM concentrations were significantly
      correlated with each other in both secretions (saliva, rp = 0.644, p = 0.001;
      tears, rp = 0.555, p = 0.009). Significantly, more Ig of all classes was secreted
      into saliva than tears as calculated by a secretory index. A large diurnal and
      day-to-day variation was observed in Ig concentrations in serial saliva and tear
      samples taken from a further four dogs. Serum Ig concentrations are therefore,
      poor indicators of mucosal secretion in this species and significant intra
      individual variation exists in secretory Ig levels. Both findings should be taken
      into account in future studies of canine mucosal immunoglobulins.

PMID- 9661262
TI  - Evaluation of neutrophilic function (chemotaxis, phagocytosis and microbicidal
      activity) in healthy dogs and in dogs suffering from recurrent deep pyoderma.
AB  - The modified Boyden's technique of chemotaxis ('leading front' method) and the
      bacterial killing test with Staphylococcus sp. stained with acridine orange were
      performed with suspensions of granulocytes from 50 healthy dogs.
      Lipopolisacharide of Escherichia coli, in normal dog serum was used as the
      chemotactic factor. The mean value for the chemotactic differential found was
      30.41 +/- 12.14 mu. The optimal concentration of bacteria and opsonins (normal
      dog serum) was 4 and 15%, respectively, and the ideal incubation period was 30
      min. The mean values obtained for phagocytosis percentage, number of bacteria per
      PMN, phagocytosis index and percentage of dead bacteria, were 97.01 +/- 3.22%,
      22.20 +/- 4.6, 21.53 +/- 4.50 and 45.30 +/- 9.18%, respectively. Granulocyte
      functions in 18 dogs with recurrent, chronic, deep pyoderma were assessed by the
      same methods. No significant difference between the two groups, for any of the
      evaluated parameters, was found. For elucidation of the pathogenesis of recurrent
      pyoderma, further studies involving humoral and cellular immunity and the
      complement system are required.

PMID- 9661263
TI  - Immunohistochemical study of the local inflammatory infiltrate in spontaneous
      canine transmissible venereal tumour at different stages of growth.
AB  - In this study, the immunohistochemical distribution of CD3 (T lymphocytes), CD79
      (B lymphocytes and plasma cells), IgG, IgM, IgA, IgG subclasses (IgG2, IgG3 and
      IgG4) L1 (macrophages) and MHC Class II antigen was analysed in the inflammatory
      infiltrates associated with spontaneous canine transmissible venereal tumours
      (CTVT) at different stages of growth. With all antibodies used, except IgM and
      IgA, the number of immunoreactive cells was significantly higher (p < 0.05) in
      the infiltrate of CTVT undergoing spontaneous regression or with stable growth
      (14 cases), than in tumours undergoing progressive growth (nine cases). This
      result suggests that T lymphocytes in addition to B cells, plasma cells
      expressing IgG, IgG2 and IgG4, and macrophages participate in the effective
      immune response against CTVT and mediate spontaneous regression of the tumour.
      MHC Class II antigen was expressed by infiltrating lymphocytes and macrophages,
      and also by fibroblasts within and around the tumours. Class II was also
      expressed by a variable number of neoplastic cells, particularly those in
      regressing or stable tumours with a marked lymphoplasmacytic infiltrate. This
      suggests that the expression of Class II by neoplastic cells is associated with
      the effective immune response and regression of CTVT.

PMID- 9661264
TI  - Effect of in vitro monocyte activation by Listeria monocytogenes antigens on
      phagocytosis and production of reactive oxygen and nitrogen radicals in bovines.
AB  - Macrophages by virtue of their phagocytic and antibacterial activities play an
      important role in the host resistance to intracellular pathogens including
      Listeria monocytogenes. However, the precise killing mechanism adopted by
      macrophages in the case of L. monocytogenes and the role of macrophage activation
      in bacterial killing are still unclear. In the present investigation, different
      antigens of pathogenic L. monocytogenes and three non-specific activators,
      namely, Lipopoly-saccharide (LPS), Phorbol Myristate Acetate (PMA) and
      Concanavalin A (ConA) supernatant were studied to adjudge their efficacy with
      regard to in vitro activation of bovine monocytes in terms of the production of
      reactive nitrogen intermediates (RNI), reactive oxygen intermediates (ROI) and
      their phagocytic index (PI). Of all the five antigens of L. monocytogenes,
      namely, viable bacteria used as live antigen (LA), heat-killed antigen (HKA),
      sonicated antigen (SA), culture filtrate antigen (CFA) and listeriolysin-O (LLO),
      LA turned out to be the best activator of monocytes for RNI as well as ROI
      production. In the PI assay, of the three antigens, that is, CFA, SA and LLO, CFA
      was found to be the best activator of phagocytosis followed by LLO and SA. Among
      non-specific activators, PMA induced the highest H2O2 production whereas LPS
      caused the maximum increase in RNI and PI production. On activation by different
      antigens of L. monocytogenes, the peripheral blood mononuclear cells (PBMCs) from
      infected animals produced significantly higher RNI than those from non-infected
      animals indicating the involvement of immune T-cells.

PMID- 9661265
TI  - Evaluation of various cytokines (IL-6, IFN-alpha, IFN-gamma, TNF-alpha) as
      markers for acute bacterial infection in swine--a possible role for serum
      interleukin-6.
AB  - A total of 64 specific pathogen free pigs were divided into eight experimental
      groups. Pigs in Group I served as non-infected controls while the other 56 pigs
      were infected intranasally with approximately 7 x 10(8) CFU of Actinobacillus
      pleuropneumoniae serotype 2 (strain 700/89) in 1 ml saline. When more than 25% of
      the infected animals showed clinical signs of disease, i.e. 20 h post infection,
      48 of the infected pigs were treated with different antibiotics (8 pigs per
      group), leaving 8 infected animals untreated. Serum samples collected 0, 10, 20,
      28 and 44 h, and 3, 4, 7, 13 and 17 days post infection were analysed for their
      content of interferon (IFN)-alpha, IFN-gamma, tumor necrosis factor (TNF)-alpha
      by immunoassays and interleukin-6 (IL-6) by a bioassay. In addition, the
      development of specific antibodies was determined in sera. Among the cytokines
      analysed, the experimental infection only induced detectable serum levels of IL
      6. The appearance of IL-6 positive animals coincided with the onset of clinical
      signs of disease and increased body temperatures. Varying levels of IL-6 (range,
      1-220 U ml-1) were detected in serum from a majority of the infected pigs (80%).
      In general, the highest levels of IL-6 were detected in serum collected for 10 or
      20 h after infection. Among the animals not treated with antibiotics, the number
      of pigs displaying IL-6 in serum continued to increase until 28 h post infection
      and then declined. The duration of the IL-6 response varied between individuals
      and lasted from eight hours to three days. Treatment with antibiotics that ceased
      the infection also terminated the IL-6 production in most of the pigs. In a pilot
      field survey, IL-6 was detected in an approximately 30% of serum samples
      collected from conventional reared pigs before allocation to finishing units.
      Thus, serum IL-6 seems to be a potential marker for ongoing bacterial infections
      in swine.

PMID- 9661266
TI  - Selective expansion and continuous culture of macrophages from adult pig blood.
AB  - Macrophages were selectively expanded and continuously cultured from adult pig
      blood. One-half ml of heparinized adult pig blood was inoculated directly into
      the medium overlaying a feeder layer of STO mouse fibroblasts. After attachment
      to the feeder cells for 24 h, the culture was washed several times with the
      medium to remove most of any unattached blood cells and re-fed. Approximately 7 x
      10(4) blood monocytes were initially detected and enumerated by specific binding
      of DiI-labeled acetylated low density lipoprotein (DiI-Ac-LDL). Macrophage
      outgrowths appeared in the primary culture after 6-7 days. The macrophages grew
      to relatively high density in 2-3 weeks (2-3 x 10(6) cells/T25 flask), and the
      culture was passaged on to fresh STO feeder layers to begin secondary culture.
      Over 2-3 months of culture the macrophage replication produced as many as 1.4 x
      10(9) DiI-Ac-LDL-positive cells. The macrophages grew on top of the feeder cells
      in two forms: either a semi-attached, round morphology, or a closely adherent,
      flat ameboid morphology with several extended pseudopods. Electron microscopic
      examination revealed the cells to be uniformly of macrophage character and that 4
      5% were giant cells. The macrophages were phagocytic and expressed CD14 on their
      surfaces. They also reacted positively with pig macrophage-specific monoclonal
      antibody (mAb), and were negative for reactivity with pig T- and B-cell-specific
      mAb. This simple method for isolating and propagating macrophages may indicate
      the replicative capacity of either adult pig blood monocytes or circulating blood
      stem cells, and it may be useful in providing macrophages for general research,
      virological assay, adoptive-immunotherapy models, and somatic gene therapy
      models.

PMID- 9661267
TI  - Polyamine-stimulated binding of diamine oxidase to DNA.
AB  - Diamine oxidase is a Cu-containing enzyme which intracellularly participates in
      the regulation of the levels of putrescine, spermidine and spermine and in this
      process produces growth inhibitory amino aldehydes and hydrogen peroxide.
      Extracellularly, the enzyme participates in the inactivation of biogenic amines,
      notably histamine. Here we present evidence that in the presence of polyamines,
      diamine oxidase has the ability to bind DNA and to oxidise DNA-bound polyamines.
      The enzyme associates with chromosomal DNA since it can be released from human
      placental DNA by treatment with DNase I and it may be involved in the degradation
      of DNA. Thus, diamine oxidase may belong to a new class of DNA-binding proteins.

PMID- 9661268
TI  - Synthesis of 3'-azolyl-2',3'-dideoxyhexose nucleosides.
AB  - 1,8-Diazabicyclo[5.4.0]undec-7-ene salts of 2-methyl-4(5)-nitroimidazole or
      benzotriazole were obtained in crystalline form. Michael-type addition of these
      salts to (4S,5R)-(E)-4,6-di-O-acetyl-5-hydroxy-2-hexenal gave, after acetylation
      of the product, an isomeric mixture of acetylated 3-(azol-1-yl)-2,3-dideoxy-D
      arabino-hexopyranosides and 3-(azol-1-yl)-2,3-dideoxy-D-ribo-hexofuranosides.
      Reaction of these peracetylated adducts with trimethylsilylated thymine in the
      presence of trimethylsilyl trifluoromethanesulfonate (TMS triflate) afforded the
      corresponding nucleosides which were deprotected by using methanolic ammonia. The
      nucleosides were found inactive against HIV-1 and HSV-1.

PMID- 9661269
TI  - Chaperone properties of calreticulin.
AB  - Calreticulin is a highly conserved protein with a relative molecular weight of
      46,000, and is mainly located in the endoplasmic reticulum. Calreticulin was
      first characterized as a calcium-binding protein in the endoplasmic reticulum,
      but since then other functions of calreticulin have been characterized, including
      chaperone and lectin properties, and regulation of integrin and nuclear hormone
      receptor activity. We have investigated the interactions between purified human
      placental calreticulin and native and denatured proteins. Our results show that
      calreticulin binds to denatured proteins in a time- and pH-dependent manner,
      which at physiological pH is dependent on divalent cations. The binding was
      dependent on the state of the denatured protein, and was highly sensitive to the
      ionic composition of the environment, being strongly inhibited by phosphate
      containing compounds. Calreticulin did not seem to distinguish between denatured
      glycosylated and non-glycosylated proteins, and was found to bind to native basic
      proteins, presumably by sheer electrostatic forces.

PMID- 9661271
TI  - Mercury content of smelt in Cayuga Lake in central New York State.
AB  - Smelt (Osmerus mordax) were netted from Cayuga Lake in Central New York State and
      analyzed for mercury concentration. There was no statistical significance (p >
      0.05) when attempting to correlate mercury concentration with fish length or
      weight for either sex. Factors affecting methylation, demethylation and
      absorption of mercury are discussed.

PMID- 9661272
TI  - Initiation and promotion of altered hepatic foci in female rats and inhibition of
      cell-cell communication by the imidazole fungicide prochloraz.
AB  - The imidazole fungicide prochloraz (1-[N-propyl-N-2-(2,4,6-trichlorophenoxy)
      ethyl carbamoyl] imidazole) was investigated for its ability to inhibit gap
      junctional intercellular communication in the scrape-loading/dye-transfer assay
      in IAR 20 rat liver epithelial cells and for effects on the initiation and
      promotion stages of hepatocarcinogenesis. Female Sprague-Dawley rats initiated
      with N-nitrosodiethylamine 24-hr after partial hepatectomy were administered
      prochloraz five days a week by oral gavage (30 or 150 mg/kg) for 10 weeks.
      Altered hepatic foci (AHF) were analyzed by quantitative stereology from liver
      sections stained for gamma-glutamyltranspeptidase (GGT) and glutathione S
      transferase P (GST-P). The fungicide was also studied for its ability to initiate
      the development of GGT-positive AHF in rat liver. The in vitro studies showed
      prochloraz to be an inhibitor of cell-cell communication in the test system used.
      In the in vivo studies, prochloraz showed no effect on the initiation of GGT
      positive foci. However, significant increases in the percentage of liver tissue
      occupied by GGT-positive AHF and the number of GST-P-positive AHF per cm3 in
      initiated animals were recorded in the low dose group. The present data suggest
      that prochloraz acts as a weak tumour promoter of hepatocarcinogenesis but does
      not initiate this process.

PMID- 9661273
TI  - N-(phenylsulfonyl)-glycine--a new contaminant in sewage- and surface water.
AB  - River samples (e.g. river Rhine, river Neckar, Germany) and samples from five
      communal sewage treatment plants were investigated for N-(phenylsulfonyl)
      glycine, -alanine and -sarcosine, as well as for the corresponding p-toluene
      analogues. As result of this screening we identified N-(phenylsulfonyl)-glycine
      as a hitherto unknown polar contaminant. In surface waters the concentrations of
      N-(phenylsulfonyl)-glycine ranged between 50 and 850 ng/l. In communal sewage
      treatment plants the concentrations varied: The substance was only found in one
      influent with a concentration of 1200 ng/l; in the biological step and in the
      effluent its concentrations ranged from 80 to 300 ng/l. N-(phenylsulfonyl)
      alanine, N-(p-toluenesulfonyl)-glycine, -sarcosine and -alanine were found
      neither in surface nor in sewage waters.

PMID- 9661274
TI  - Congener-specific analysis of PCBs in human milk from Kazakhstan.
AB  - We have characterized the spectrum of PCB contaminants in human milk samples from
      95 women in Kazakhstan using GC/MS congener specific analysis. In these samples,
      12 PCBs comprised 83% of total PCB concentration, and were similar to the major
      PCBs reported in other published human milk studies. By summing concentration
      levels of 80 PCB congeners in the Kazakhstan samples, a mean total PCB
      concentration of 368 ng/g fat was obtained. This is lower than levels reported in
      human milk samples from Western Europe. Six indicator PCBs were summed in Kazakh
      milk samples; their aggregate value was similar to literature values published
      for human milk from the former Soviet Union. Using WHO's recent TEF scheme, the
      mean sum of PCDD/F, coplanar PCB, mono-ortho PCB, and di-ortho PCB TEQ is 42 pg
      TEQ/g fat.

PMID- 9661275
TI  - Application of a Finnish mutagenicity model to drinking waters in the U.S.
AB  - Recent epidemiological studies conducted in Finland have reported a positive
      correlation between the mutagenicity of chlorinated drinking waters and certain
      human cancers. In these studies, past exposure to drinking water mutagenicity was
      assessed using a model developed by Vartiainen et al. [1] based on data collected
      in Finland. In this model, mutagenicity, as determined in the Ames assay, is a
      function of the total organic carbon (TOC) concentration of the water, chlorine
      dose, and to a minor extent, the concentration of ammonia. A study has been
      initiated to assess the applicability of this model to source waters and water
      treatment practices in the United States. Water samples were collected from three
      full-scale treatment plants and one pilot-scale plant. All the plants used
      chlorine exclusively for disinfection. One full-scale plant used ground water.
      Surface water sources were used by the other plants. TOC and ammonia
      concentrations were determined analytically and chlorine doses were obtained from
      the treatment plants. The water samples were concentrated by XAD resin adsorption
      for testing in the Ames assay. The observed levels of mutagenicity in the
      finished waters were 1.5 to 2-fold higher than those predicted using the model as
      specified in Vartiainen et al. [1]. Consequently, further validation is needed
      prior to widespread use of the Finnish model to assess exposure to mutagenicity
      in chlorinated drinking waters in the United States.

PMID- 9661276
TI  - The use of heavy metal soil analysis for archaeological surveying.
AB  - An evaluation of the geochemical analysis of soils as an archaeological
      investigative technique is illustrated with reference to a site with a known
      history of human use and settlement. The results show certain elements, including
      the heavy metals Pb, Zn, Cd, Cu etc., to be associated with locations of past
      human activity, and support such analyses as significant additions to the means
      by which archaeologists might investigate the archaeological record.

PMID- 9661277
TI  - Pretreatment and biodegradability enhancement of DSD acid manufacturing
      wastewater.
AB  - Two advanced oxidation processes, Fenton's reagent oxidation and ozonation, were
      used for pretreatment of a 4,4'-diaminostilbene-2,2'-disulfonic acid (DSD-acid)
      manufacturing wastewater on a laboratory scale. The results showed that both
      methods are suitable for partial removal of chemical oxygen demand (COD) and
      color as well as the enhancement of biodegradability of DSD-acid manufacturing
      wastewater before the conventional biological treatment. Fenton's reagent
      oxidation by 9.0 g/L H2O2 and 150 mg/L Fe2+ and ozonation by 7.5 g/L O3 led to an
      improved biodegradability (BOD5/COD = 0.3). Fenton's reagent oxidation in
      combination with Fe3+ coagulation has shown to effectively remove COD and color.
      About 90% of COD and 95% of color removals were obtained at the optimum
      condition, oxidation by 150 mg/L Fe2+ and 2 g/L H2O2, followed by two-stage
      coagulation with 5 g/L and 2 g/L FeCl3, respectively.

PMID- 9661278
TI  - Biodegradation of anthracene by soil fungi. Groupe pour l'Etude du Devenir des
      Xenobiotiques dans l'Environnement (GEDEXE).
AB  - A selection of 39 strains of micromycetes known as good degraders of
      polychlorinated aromatic compounds, mostly isolated from soil and belonging to
      various taxonomic groups, have been investigated for anthracene degradation.
      Toxicity and consumption assays, first evaluated on solid media, have not shown
      any toxicity of anthracene (1-100 mg.L-1) towards fungi. Degradation of
      anthracene (10 mg.L-1) was then investigated in a liquid synthetic medium for 4
      days and evaluated by HPLC. Among the 39 strains tested, 19 degraded anthracene
      at 50% or more. Zygomycetes appeared to be the most efficient group (mean
      degradation : 81%) while Melanconiales were the least efficient (mean: 14%).
      Among 19 efficient strains, 8 had not yet been reported in the literature:
      Cryphonectria parasitica, Ceriporiopsis subvermispora, Oxysporus sp.,
      Cladosporium herbarum, Drechslera spicifera, Verticillium lecanii, Fusarium
      moniliforme var. subglutinans and Rhizopus arrhizus.

PMID- 9661279
TI  - Biodegradation of the herbicide Diuron in soil by indigenous actinomycetes.
AB  - Three actinomycete strains isolated from soil treated with 2,4-D were able to
      degrade the herbicide Diuron in vitro. Strain CCT 4916 was the most efficient,
      degrading up to 37% of applied Diuron (100 mg Kg-1 soil) in 7 days, as measured
      by HPLC and UV/VIS spectroscopy. All strains showed protease and urease activity;
      intracellular activity of metapyrocatechase and pyrocatechase were not found.
      Actinomycete strain CCT 4916 produced manganese peroxidase, which could be
      potentially related to degradation of Diuron.

PMID- 9661280
TI  - Stochastic effects in a model of nematode infection in ruminants.
AB  - We illustrate the importance of stochastic effects in population models of
      biological systems and demonstrate a number of analytic and simulation-based
      approaches that can usefully be applied to such models. In so doing, we compare
      the stochastic approach to the more usual deterministic one. The model studied
      represents the gastrointestinal infection of ruminants by nematodes when the
      hosts maintain a fixed density. The incorporation of a feedback mechanism, which
      accounts for the immune response of the infected animals, results in a highly
      nonlinear model; similar forms of nonlinearity are a feature of many plausible
      models in population biology. In the absence of an analytic solution to the full
      stochastic model we explore a number of approximations and compare them to
      simulations of the full stochastic process. We explore three modes of behaviour
      of the system. In the endemic regime the stochastic system fluctuates widely
      around the non-zero fixed points of the deterministic model. In the managed
      regime, where the system is subject to external periodic perturbation, stochastic
      effects are negligible. Finally, we find that in a regime in which the
      deterministic model predicts the long-term persistence of oscillations the
      stochastic model shows that extinction can occur. Of the approximation procedures
      we consider, the Normal approximation to the full stochastic process is the most
      generally applicable, and it is also the most accurate in the light of simulation
      results. Local linearization provides reasonably accurate prediction of the
      variance-covariance structure, and a transfer function approach allows
      calculation of the time-lagged auto- and cross-correlations in the endemic
      regime. Linearization of the stochastic updates themselves results in poor
      prediction of the population variances.

PMID- 9661281
TI  - Mathematical modelling of the release of drug from porous, nonswelling
      transdermal drug-delivery devices.
AB  - A general model is presented for the release of drug from porous nonswelling,
      transdermal drug-delivery devices and it is shown to reduce to previously
      proposed models in suitable limits. The processes which govern the release of
      drug are considered to be diffusion of dissolved drug and dissolution of
      dispersed drug, both in the body of the device and in the device pores, and
      transfer of drug between the two domains. In the classical limit of large
      dissolution rates, the problem reduces to one of the moving-boundary type, and
      solution of this problem in the case where the initial drug loading is much
      greater than the drug solubility in the device yields expressions for the flux of
      drug to a perfect sink (modelling in vitro conditions). It is shown that
      behaviour greatly differing from the classical first-order drug delivery (alpha t
      1/2) may be exhibited, depending upon the parameter regime. In some situations
      the dissolution rates may not be so large and solutions of the general model are
      derived in the case where the dispersed drug is considered to be undepleted and
      the diffusivity in the solvent-filled pores is much larger than in the body of
      the delivery device. Numerical studies are undertaken, and the coupling of
      delivery device and skin-diffusion models (in order to model the complete
      transdermal drug-delivery process) is also considered.

PMID- 9661282
TI  - Modelling the macrophage invasion of tumours: effects on growth and composition.
AB  - Even in the early stages of their development, tumours are not simply a
      homogeneous grouping of mutant cells; rather, they develop in tandem with normal
      tissue cells, and also recruit other cell types including lymphatic cells and the
      endothelial cells required for the development of a blood supply. It has been
      repeatedly seen that macrophages form a significant proportion of the tumour
      mass, and that they can have a variety of effects upon the tumour, leading to a
      delicate balance between growth promotion and inhibition. This paper develops a
      model for the early, avascular growth of a tumour, concentrating on the
      inhibitory effect of macrophages due to their cytolytic activity. It is shown
      that such an immune response is not sufficient to prevent growth, due to it being
      a second-order process with respect to the density of the tumour cells present.
      However, the presence of macrophages does have important effects on the tumour
      composition, and the authors perform a detailed bifurcation analysis of their
      model to clarify this. An extended model is also considered which incorporates
      addition of exogenous chemical regulators. In this case, the model admits the
      possibility of tumour regression, and the therapeutic implications of this are
      discussed.

PMID- 9661283
TI  - Spectroscopic and functional studies of a novel quadruple myoglobin variant with
      increased peroxidase activity.
AB  - A quadruple variant of horse heart myoglobin
      (Thr39Ile/Lys45Asp/Phe46Leu/Ile107Phe) that exhibits significantly (approximately
      25-fold) greater peroxidase activity than the wild-type protein has been studied
      to determine its midpoint reduction potential (24(2) mV vs. SHE; pH 6.0, mu = 0.1
      M, 25 degrees C) and to characterize the kinetics of its reaction with hydrogen
      peroxide. In addition, Fourier transform infrared (FTIR) spectra of the carbonyl
      and azide adducts of the protein have been obtained to gain initial insight into
      the effects of these substitutions on the ligand binding properties of the
      reduced and oxidized variant. All of the results obtained in this work are
      consistent with a variant heme binding pocket with increased hydrophilic
      character.

PMID- 9661284
TI  - Cd2+ effects on respiration and swelling of rat liver mitochondria were modified
      by monovalent cations.
AB  - Changes in Cd2+ effects on respiration of succinate-energized rat liver
      mitochondria were studied after replacement of 100 mM KCl in an incubation medium
      by equimolar amounts of NaCl or LiCl, or by 200 mM sucrose. In KCl medium, 2.5-10
      microM Cd2+ decreased the state 3 and 2,4-dinitrophenol (DNP)-stimulated
      respiration of mitochondria, and increased their respiration in the state 4,
      however, 10-40 microM Cd2+ diminished the state 4 respiration. Compared to the
      experiments with KCl medium, it was demonstrated that Cd2+ effects on the
      mitochondrial respiration was increased in NaCl medium, decreased in sucrose
      medium, and unchanged in LiCl medium, except that 10-25 microM Cd2+ decreased the
      state 4 respiration of mitochondria in the same way as in the NaCl medium. Cd2+
      (20 microM) stimulated an extensive swelling of nonenergized mitochondria
      incubated in 125 mM nitrate media, the effect being increased in the series of Li
      < Na < K < NH4. Swelling of succinate-energized mitochondria incubated in K
      acetate medium was additionally stimulated by 10 microM Cd2+. The initially low
      swelling of succinate-energized mitochondria in the KCl medium increased with
      increase in Cd2+ concentrations in this medium. Differences found in the Cd2+
      effects on respiration and on swelling of mitochondria incubated in the media
      used are discussed in terms of general ion permeabilities and differences in Cd2+
      binding, its uptake, and interaction with respiratory enzymes.

PMID- 9661285
TI  - Novel approaches to prodrugs of anticancer diaminodichloroplatinum(II) complexes
      activated by stereoselective enzymatic ester hydrolysis.
AB  - A series of dichloro(ethylenediamine)-type platinum complexes bearing ester-,
      amide- and ether-bonded alkyl straight chains (C2-C18) was prepared as a model
      for the prodrug of cis-diamminedichloroplatinum (CDDP). Evaluation of cytotoxic
      activity of the complexes against the S-180 cell line proved that their enzymatic
      hydrolysis in the cells lowered the permeability to the cell membranes resulting
      in an increase of pharmacological activity. Optically active isomers of
      dichloro(N-2(2-phenylpropanoyloxy)ethyl)-2,3-diaminopropanamide )platinum(II)
      were prepared. They were re-activated stereoselectively, and a tenfold difference
      in activity was observed based on the differences in chiral discrimination by
      enzymes.

PMID- 9661286
TI  - Multi-metal binding site of serum albumin.
AB  - Circular dichroism and electron spin resonance spectroscopy are used to
      investigate the second specific metal binding site on human, bovine and porcine
      albumins. Ni(II), Zn(II) and Cd(II) can displace Cu(II) from the second Cu(II)
      site but not from the first strong site of human and bovine albumins (the N
      terminal site). The second Cu(II) binds more strongly than the other metal ions
      to the second site of all three proteins, except Zn(II) binding to porcine
      albumin which is ca. 10 x stronger than Cu(II). The second Cu(II) site appears to
      be a tetragonal ?2N, 4O? site.

PMID- 9661287
TI  - Targeting of tetrathiomolybdate on the copper accumulating in the liver of LEC
      rats.
AB  - The uptake of tetrathiomolybdate (TTM) by the liver and the removal of copper
      (Cu) accumulating in the liver in a form bound to metallothionein (MT) by TTM
      were studied in Long-Evans cinnamon (LEC) rats, an animal model of Wilson
      disease, in order to develop better treatments for the disease and Cu toxicity.
      Although molybdenum (Mo) was incorporated in a dose-dependent manner into the
      livers of both LEC and Long-Evans agouti (LEA) rats, the original strain of LEC
      rats used as a reference animal, the uptake into the liver of LEC rats was 13
      times higher than that in LEA rats. The concentration of Mo in the soluble
      fraction plateaued and it was distributed more in the insoluble fraction with a
      higher dose in LEC rats. The concentration of Cu in the whole livers of LEC rats
      was decreased by TTM in a dose-dependent manner only at lower doses. However, the
      concentration of Cu in the soluble fraction continued to decrease with the dose
      of TTM. The results can be explained in terms of complex formation. Namely, TTM
      forms a complex with Cu, tentatively referred to a Cu/TTM complex, that can be
      effluxed into the bloodstream, and then binds selectively to albumin when the
      dose of TTM is low. On the other hand, TTM forms an insoluble complex, named as a
      Cu/TTM polymer that is precipitated in the liver when the dose is high. The
      results further indicate that TTM taken up by a cell is immobilized in the cell
      through the dose-dependent formation of a complex containing Cu, Mo and sulfur
      (S), which causes further uptake of TTM. TTM injected into rats or incubated in
      vitro with serum does not remove Cu from ceruloplasmin. TTM is, thus, suggested
      to target a cell accumulating excess Cu as Cu-MT, and to remove Cu selectively
      without interacting with Cu in Cu-enzymes. The results indicate that TTM is taken
      up by the liver depending on the amount of Cu accumulating in the form of MT, and
      then Cu is effluxed together with Mo in the form of Cu/TTM complex into the
      bloodstream.

PMID- 9661288
TI  - Anti-inflammatory properties of diclofenac transition metalloelement complexes.
AB  - As part of our research into understanding drug-metalloelement interactions, we
      have prepared complexes of Cu(II), Co(II), Ni(II), Mn(II), Fe(II), Fe(III), and
      Pd(II) with Diclofenac, in order to investigate their anti-inflammatory activity.
      Their inhibitory effects on rat or mouse paw edema induced by Carrageenan, Con-A,
      Nystatin, and Baker's yeast were compared with those of Diclofenac. Furthermore,
      the action of Diclofenac's metalloelement complexes on phagocytosis of yeast by
      rat peritoneal cells, as well as the capacity of some of the metalloelement
      complexes to inhibit lipid peroxidation of liver microsomal membranes was also
      investigated. These complexes exhibited a strong inhibitory effect on Carrageenan
      , ConA-, and Nystatin-induced edemas (35-80% inhibition) comparable to the
      inhibition caused by Diclofenac (61-76% inhibition). Furthermore, complexes with
      Co(II), Ni(II), Pd(II), and Mn(II) were found to have an anti-inflammatory
      profile (35-50% inhibition) superior to diclofenac (17% inhibition) when
      inhibiting inflammations due to Baker's yeast, the mechanism of which involves
      mainly the activation of lipoxygenase and/or complement system. Complexes of
      Ni(II) and Pd(II), which showed significant inhibition of induced-edemas in rats,
      were also tested in mice at lower and higher doses and showed a significant dose
      dependent inhibition of edemas in mice. Some of these complexes also interfere
      with in vitro phagocytosis. The most active anti-inflammatory complexes Co(II),
      Pd(II), and Ni(II), also offered significant protection against lipid
      peroxidation in vitro, acting as antioxidant compounds, properties that are not
      demonstrated by Diclofenac. Finally, it is noted that almost all metalloelement
      complexes of Diclofenac showed high anti-inflammatory activity at molecular
      concentrations much lower than that of Diclofenac. From the present study it is
      suggested that the anti-inflammatory activity of Diclofenac is enhanced by the
      formation of coordination complexes with transition metalloelements.

PMID- 9661289
TI  - Fine structure of the retinal photoreceptors of the emu (Dromaius
      novaehollandiae).
AB  - The retinal photoreceptors of the emu (Dromaius novaehollandiae) consist of rods,
      single cones and double (unequal) cones present in a ratio of about 10:1:4
      respectively. The rods are long slender cells which are felt to undergo
      retinomotor movements. The rod outer segment is a stack of bimembranous discs
      which display shallow peripheral incisures and are all of the same diameter. The
      rod inner segment displays an ellipsoid of mitochondria, much rough endoplasmic
      reticulum (ER), numerous polysomes and a prominent hyperboloid of glycogen.
      Single cones show a tapered outer segment, no oil droplet but a large ellipsoid
      with several small lipid droplets and a paraboloid of glycogen. Double cones
      consist of a chief member which displays a single large heterogeneous oil droplet
      and no paraboloid, and an accessory cone which has no oil droplet but again
      several small lipid droplets and a large paraboloid. All cones show a large
      ellipsoid, plentiful polysomes, rough ER, Golgi zones and autophagic vacuoles.
      Along the length of the contiguous membranes of the two members of the double
      cones are scattered membrane densifications. The cones are not believed to
      undergo retinomotor movements in the emu. Rod photoreceptors are relatively small
      in diameter and hence are closely packed, while the larger cones are not as
      abundant. Rods and cones (both types) display both invaginated (ribbon) synapses
      as well as numerous superficial (conventional) synaptic sites.

PMID- 9661290
TI  - Fine structure of the retinal epithelium (RPE) of the emu (Dromaius
      novaehollandiae).
AB  - As part of an ongoing comparative fine structural study, the retinal pigment
      epithelium (RPE), choriocapillaris and complexus basalis (Bruch's membrane) in
      the emu (Dromaius novaehollandiae) have been investigated by light and electron
      microscopy. The RPE consists of a single layer of cuboidal cells joined basally
      by a series of tight junctions. Basally (sclerally) the RPE cells display
      numerous deep infoldings while apically (vitreally) plentiful microvillar
      processes interdigitate with the photoreceptor outer segments. Internally the
      epithelial cells show a large vesicular nucleus, plentiful smooth endoplasmic
      reticulum (SER) and numerous polysomes, but very little rough endoplasmic
      reticulum (RER). Numerous pleomorphic mitochondria are predominantly basally
      located. In the light-adapted specimens studied, the melanosomes of the RPE are
      almost exclusively located within the apical processes of these cells. Phagosomes
      and lysosome-like bodies are also present, as are myeloid bodies which often
      display ribosomes on their outer surface. Bruch's membrane (complexus basalis) is
      typical of avian species in that it is pentalaminate and the central lamina densa
      is displaced towards the choriocapillaris. The choricocapillaris endothelium is
      attenuated but only minimally fenestrated facing Bruch's membrane. Most of these
      fenestrations show a single-layered diaphragm but fenestrations with a double
      layered diaphragm are not uncommon.

PMID- 9661291
TI  - Fine structure of the pecten oculi of the emu (Dromaius novaehollandiae).
AB  - The pecten oculi of the emu (Dromaius novaehollandiae) has been examined by light
      and electron microscopy. In this species the pecten is small relative to the size
      of the globe and is of a primitive pleated type. It consists of only 3-4 loose
      folds that are joined apically by a bridge of tissue which holds the pecten in a
      fan-like shape widest at its base. Each fold is quite thick (100-120 microns) and
      has a central core of mostly unpigmented cell processes. In this central region
      are supply or drainage vessels while numerous melanocytes and pecteneal
      capillaries are only located at the periphery of the folds. The capillaries are
      extremely specialized for transport functions and for the most part display
      extensive microfolds on both their luminal (inner) and abluminal (outer) borders
      although capillaries with very few microfolds are also noted. An unusual feature
      of some capillaries is luminal folds of the cell body with further luminal
      microfolds superimposed on them. Except for the nuclear region which contains
      most of the organelles, the endothelial cell bodies are extremely thin. These
      capillaries are surrounded by thick fibrillar basal laminae which are felt to be
      structurally important. Pericytes are a common feature within the basal lamina of
      these capillaries. The numerous peripherally located melanocytes which more or
      less surround the capillaries are also presumed to be important for structural
      support of the pecten. The large number of cell processes forming the central
      core of each fold are felt to be unpigmented processes of the melanocytes.

PMID- 9661292
TI  - Morphological organization of neuropile glial cells in the central nervous system
      of the medicinal leech (Hirudo medicinalis).
AB  - Neuropile glial (NPG) cells in the central nervous system of the medicinal leech,
      Hirudo medicinalis, were studied by histological, histochemical and
      immunocytochemical techniques. The NPG cells are often surrounded by electron
      dense microglial cells. The central cytoplasm of NPG cells shows a significant
      zonation. The zone around the nucleus contains mitochondria, glycogen and
      vesicles. The cytoplasm also contains many ribosomes, a few dictyosomes and
      distinct inclusions up to 2 microns in diameter. A second zone around the
      perinuclear region is marked by the occurrence of bundles of intermediate
      filaments that correspond in thickness to glial filaments of vertebrates. We
      found a positive reaction with polyclonal antibodies against human glial
      fibrillary acidic protein (GFAP), and the areas of intense fluorescence
      correspond to the regions where intermediate filaments were found to be abundant.
      The peripheral zone contains numerous membrane stacks that could not be
      contrasted by lanthane nitrate or tannic acid. Therefore, the membrane stacks
      could be part of an extensive smooth endoplasmic reticulum, which is
      characteristic of cells with active lipid metabolism.

PMID- 9661293
TI  - Immunohistochemical localization of ecdysteroid receptor and ultraspiracle in the
      epithelial cell line from Chironomus tentans (Insecta, Diptera).
AB  - Ecdysteroid receptor (EcR) and its heterodimerization partner, ultraspiracle
      (USP), were demonstrated in the epithelial cell line from Chironomus tentans by
      immunohistochemistry. In untreated cells both proteins are present in nuclei as
      well as in granular compartments of the cytosol. At 1 day after addition of 1
      microM 20-OH-ecdysone (20E) total immunofluorescence had increased in the nuclei,
      whereas the cytoplasmic staining had disappeared. At the 2nd and 3rd days all
      cells within a vesicle appear identical according to morphological criteria, but
      the EcR and USP immunoreactivity becomes restricted into patches of neighbouring
      cells. The hormonally induced changes in the pattern of localization of
      functional ecdysteroid receptor, the heterodimer of EcR and USP, are discussed in
      relation to similar effects of 20E on acetylcholinesterase and muscarinic
      acetylcholine receptor distribution in this cell line.

PMID- 9661294
TI  - Ultrastructure of the larval tentacle and its skeletal muscle in Xenopus laevis.
AB  - During premetamorphic development, tadpoles of Xenopus laevis possess a
      transitory pair of long, slender, mobile tentacles situated at the corners of the
      mouth. Microscopic examination of the larval tentacle typically reveals three
      distinct compartments: a central core of cartilage, a laterally situated skeletal
      muscle, and a nerve supply medially. Along the length of each tentacle, the
      epidermis is supplied by many unmyelinated nerve fibers, presumably sensory in
      nature, which terminate as naked axons in close association with the epidermal
      cells. The striated tentacular muscle, in the proximal region of the lateral
      compartment, consists of extrafusal muscle fibers of varying size which range in
      number from 36 to 48 per tentacle (n = 10). Using morphometric criteria, we have
      classified the skeletal muscle fibers of the larval tentacular muscle into three
      types: large (30-50 microns), intermediate (20-30 microns), and small (10-20
      microns). By electron microscopy, each type displays characteristic sarcomeric
      banding patterns, sarcotubular and mitochondrial disposition, and motor endplate
      ultrastructure. Our morphological observations indicate that the tentacles of the
      Xenopus tadpole are complex mobile facial extensions which may play roles in
      mechanoreception and/or chemoreception during the waterborne stages of
      development. Because of its transitory nature, the Xenopus tentacle may be a
      useful experimental model in future studies of neuromuscular development and
      subsequent regression in a relatively short period of time.

PMID- 9661295
TI  - Effect of substratum on growth, cell morphology and lactoferrin synthesis and
      secretion in bovine mammary cell culture.
AB  - The role of extracellular matrix in morphology, growth and lactoferrin synthesis
      and secretion in bovine mammary cells from a developing gland is poorly defined.
      In this study, bovine mammary cells from a hormone-primed developing gland were
      isolated and cultured on plastic, collagen, embedded within collagen, or on EHS
      matrix, with the hormones prolactin, insulin, and cortisol in the presence or
      absence of fetal calf serum. Mammary cells on plastic or collagen spread and
      formed confluent cells sheets, while those embedded within collagen or on EHS
      matrix maintained their acinar-like structure. Histological and ultrastructural
      analysis of cells showed that cells on plastic and collagen grew in multilayers,
      while those embedded within collagen or on EHS-matrix lacked any lumen structure.
      The ultrastructure of cells on different substrata more resembled an
      undifferentiated phenotype. Mammary cells secreted lactoferrin in increasing
      concentrations throughout the culture period. The total amount secreted in
      culture was regulated by extracellular matrix and fetal calf serum. Cells
      embedded within collagen in serum-free cultures secreted the lowest amounts of
      lactoferrin (up to 619 ng/ml; day 14), while those on collagen and supplemented
      with fetal calf serum secreted up to 4920 ng/ml at day 14. Fetal calf serum
      induced higher lactoferrin secretion within each substratum on which the cells
      were cultured. No intracellular accumulation of lactoferrin was noted in cells on
      plastic or collagen or those embedded within collagen, whereas those on EHS
      matrix accumulated more than 500 ng/ml of lactoferrin
      intracellularly/intracinarly. Furthermore, when cultured on a similar substratum,
      cells from a developing gland secreted higher lactoferrin than cells from a
      lactating gland.

PMID- 9661296
TI  - Morphological and electrical characteristics of postnatal hippocampal neurons in
      culture: the presence of bicuculline- and strychnine-sensitive IPSPs.
AB  - A modified method was developed for tissue-culturing postnatal hippocampal
      neurons using simple mechanical trituration for cell isolation and not including
      any hydrolysing enzymes, nerve growth factors or antiproliferating agents. The
      morphological properties of such neurons were characterized with light and
      interference polarizing microscopy, which revealed the appearance of growth cones
      from peripheral neurons and the presence of different types of neurons, including
      bipolar, stellate and pyramidal-like cells (i.e., pyramidal and dentate gyrus
      granule cells), which could be related to their putative counterparts in intact
      brain. The whole-cell configuration of the patch-clamp method was used for
      electrophysiological recordings of inhibitory synapses between these dissociated
      cultured neurons from the early postnatal rat hippocampus. This study indicated
      the presence of tetrodotoxin (TTX)-sensitive and TTX-resistant inhibitory
      postsynaptic potential (IPSPs) and inhibitory postsynaptic currents (IPSCs) in
      current-clamp and voltage clamp modes respectively. The coincident reversal
      potentials for IPSCs and for GABAA and glycine-evoked currents, and the
      sensitivity of the IPSCs to bicuculline or strychnine, indicated that these IPSCs
      were Cl-(-)dependent and mediated by either GABAA or glycine receptors.
      Inhibitory postsynaptic currents recorded under voltage-clamp conditions decayed
      with a time course that could be fitted by a single exponential with a value of
      26 ms. An average quantal content of 2.5 was responsible for a typical GABA and
      glycine-activated IPSC and a single quantum for GABAergic input was inferred to
      activate about 160, and for glycinergic, about 200 Cl-, channels.

PMID- 9661297
TI  - Glycogen-forming function of hepatocytes in the rat regenerating cirrhotic liver
      after a partial hepatectomy.
AB  - Rat liver punctate biopsies were used for cytofluorimetric determinations of the
      content of glycogen and its fractions in hepatocytes, and also for microchemical
      measurements of the activity of glucose-6-phosphatase, glycogen phosphorylase,
      and glycogen synthase, in liver tissue with cirrhosis produced by carbon
      tetrachloride (CCl4) poisoning, during regeneration of the liver after the
      cessation of poisoning and after a partial resection of the cirrhosed liver. The
      liver cirrhosis was shown to be characterized by an accumulation of glycogen
      (predominantly of its metabolically less active fraction) in hepatocytes and by a
      decrease in the activities of the glycogenolytic enzymes in the liver parenchyma.
      On the cessation of poisoning, there was a partial or complete return to normal
      levels of the glycogen metabolism parameters. Some of them returned to normal
      more quickly if a partial hepatectomy was performed after the cessation of
      poisoning.

PMID- 9661298
TI  - Sertoli cell nuclear pore number changes in some stages of the spermatogenic
      cycle of the rat seminiferous epithelium.
AB  - In an earlier study we described changes in the number and distribution of
      nuclear pores during maturation of germ cells at given stages of the
      spermatogenic cycle; these changes were related to the activity of nucleus
      cytoplasm transport. Similarly, the present work was performed by combining
      freeze-fracture techniques with Sertoli nuclei identification criteria, using
      fragments of tubules isolated by transillumination under stereomicroscopy. We
      studied the density of nuclear pores in freeze-fracture replicas of the Sertoli
      nuclear envelope at stages XIII-XIV-I compared with stages IX-XII. Pore counts
      were carried out on photographs of the platinum replicas using a digitalized
      morphometric board. The results were statistically analyzed using Student's t
      test. The difference in density (pore number/micron2 +/- SEM) was significant
      between stages IX-XII (8.25 +/- 0.63) and XIII-XIV-I (10.80 +/- 0.60). We
      postulate that this density appears to be increased at the time of increased
      metabolic requirements of the Sertoli cell.

PMID- 9661299
TI  - Exchangeability of actin in cardiac myocytes and fibroblasts as determined by
      fluorescence photobleaching recovery.
AB  - Rhodamine (Rho)-labeled muscle and non-muscle actins were microinjected into
      cultured embryonic chicken cardiac myocytes and fibroblasts. After incorporation
      of the fluorescent actin analog into cellular structures, small areas of labeled
      structures were photobleached with a laser pulse, and fluorescence recovery (FR)
      was measured to determine the exchangeability of isoactins in these structures.
      With both Rho-muscle and Rho-non-muscle actins, the FR rate in any part of stress
      fibers was consistently faster than that observed in any part of myofibrils.
      Thus, although non-striated (proximal and terminal) portions of nascent
      myofibrils are similar in appearance and composition to stress fibers, our data
      clearly revealed differences in actin stability between these two structures.
      Further, although cardiomyocytes were incapable of discriminating between the
      incorporation of muscle and non-muscle actin isoforms into myofibrils, FR after
      photobleaching of Rho-muscle actin was faster than that of Rho-non-muscle actin
      in immature non-striated portions. This indicates that actin molecules in cardiac
      myofibrils cannot be readily exchanged by heterotypic non-muscle actin.
      Fluorescently labeled actin incorporated into non-striated (proximal and
      terminal) portions of myofibrils and terminal portions of stress fibers was found
      to be more stable than alpha-actinin. The relative stability of actin could
      facilitate the formation of nascent Z-bands of myofibrils and the reorganization
      of stress fibers at these portions.

PMID- 9661300
TI  - Vascular endothelium of human dental pulp expresses diverse adhesion molecules
      for leukocyte emigration.
AB  - The expression of adhesion molecules on the vascular endothelium of healthy and
      inflamed human dental pulp was studied immunohistochemically using antibodies for
      selectin family and immunoglobulin super-family members. In healthy dental pulp,
      some vessels reacted very weakly with major histocompatibility complex (MHC)
      class II, and E- and P-selectin, and many vessels reacted with platelet
      endothelial cell adhesion molecule-1 (PECAM-1), but no vessels reacted with
      intercellular adhesion molecule-1 (ICAM-1), ICAM-3 and vascular cell adhesion
      molecule-1 (VCAM-1). In inflamed pulp, a large number of vessels reacted strongly
      with MHC class II, E- and P-selectin, PECAM-1, ICAM-1, ICAM-3, and VCAM-1. This
      indicates that the vascular endothelium of the inflamed human dental pulp
      expresses diverse adhesion molecules for leukocyte emigration from the blood
      stream into tissue. Dental pulp is surrounded by dentin and isolated from other
      tissue, like an in vitro system, so dental pulp is an attractive model for
      studying the roles of adhesion molecules on the vascular endothelium in
      transendothelial migration of leukocytes.

PMID- 9661301
TI  - Evaluation of the allergenicity of spore and mycelia extracts of Pisolithus
      tinctorius.
AB  - The antigenic and allergenic chemical analysis of spore and mycelia extracts of
      Pisolithus tinctorius was carried out. The spores were collected from
      basidiocarps in plantations of Eucalyptus spp and the mycelia from culture in MNM
      medium. With basis on the fungus growth curve, the mycelia masses were obtained
      after 10, 20, 30, and 40 days of incubation, which correspond, respectively, to
      the beginning, middle and end of the log phase, and beginning of the decline
      phase. The mycelia masses, together with the spores, were submitted to the action
      of three extractors (Coca, Tris-HCl, and ammonium bicarbonate). The contents of
      carbohydrates and proteins were determined. The SDS-PAGE electrophoretical
      analysis revealed separate fractions in these extracts, besides common fractions,
      in function of cultivation time and extraction methods. The selected extracts for
      the allergic tests were the ones with the highest number of fractions. The prick
      tests were conducted in 374 patients--rural workers, eucalyptus plantation
      workers, and college students. The positivity to the "prick test" with the
      antigenic extract of P. tinctorius was, respectively, 3.78%, 28.20% and 6.40%.
      Most prick-test positive patients (82.75%) also presented symptoms of respiratory
      allergy (asthma and rhinitis). There was no reactivity difference when the spore
      and mycelia extracts were employed. The analysis of the positive patients' sera
      revealed the presence of IgE specific to the P. tinctorius antigens. Since
      Pisolithus tinctorius is found as mycorrhiza of Eucalyptus spp, and this plant is
      used in reforestation in most countries, the importance of that fungus should be
      regarded as a possible cause of respiratory allergies, especially in
      occupationally exposed workers.

PMID- 9661302
TI  - Cross-reactions between Toxocara canis and Ascaris suum in the diagnosis of
      visceral larva migrans by western blotting technique.
AB  - Visceral larva migrans (VLM) is a clinical syndrome caused by infection of man by
      Toxocara spp, the common roundworm of dogs and cats. Tissue migration of larval
      stages causes illness specially in children. Because larvae are difficult to
      detect in tissues, diagnosis is mostly based on serology. After the introduction
      of the enzyme-linked immunosorbent assay (ELISA) using the larval excretory
      secretory antigen of T. canis (TES), the diagnosis specificity was greatly
      improved although cross-reactivity with other helminths are still being reported.
      In Brazil, diagnosis is routinely made after absorption of serum samples with
      Ascaris suum antigens, a nematode antigenically related with Ascaris lumbricoides
      which is a common intestinal nematode of children. In order to identify T. canis
      antigens that cross react to A. suum antigens we analyzed TES antigen by SDS-PAGE
      and Western blotting techniques. When we used serum samples from patients
      suspected of VLM and positive result by ELISA as well as a reference serum sample
      numerous bands were seen (molecular weight of 210-200 kDa, 116-97 kDa, 55-50 kDa
      and 35-29 kDa). Among these there is at least one band with molecular weight
      around 55-66 kDa that seem to be responsible for the cross-reactivity between T.
      canis and A. suum once it disappears when previous absorption of serum samples
      with A. suum antigens is performed.

PMID- 9661303
TI  - Histoplasmin reaction. Comparison of a polysaccharide antigen to the filtrate
      antigen.
AB  - This work was planned by taking into account all the knowledge accumulated from
      the immunological study of paracoccidioidomycosis. It aimed at comparing a
      polysaccharide antigen from Histoplasma capsulatum to a classic histoplasmin with
      the help of intradermal tests of delayed type of hypersensitivity. Tests were
      applied to 115 individuals in Santo Amaro, a town in the State of Sao Paulo.
      Positive results using classic histoplasmin were obtained in 46.0% cases whereas
      positive results using the polysaccharide antigen at its highest concentration
      were obtained in 51.30% cases. The major conclusion in this investigation is that
      it is possible to use the polysaccharide antigen as histoplasmin instead of the
      filtrate antigen.

PMID- 9661304
TI  - Serological follow-up of patients with paracoccidioidomycosis treated with
      itraconazole using Dot-blot, ELISA and western-blot.
AB  - Twenty-seven mycologically proven cases of paracoccidioidomycosis (PCM) were
      treated with itraconazole (100-200 mg/day in month 1 and 100 mg/day until month 6
      8) and evaluated clinically and serologically, up to 3.5 years post-therapy,
      using Dot-blot and ELISA for measuring the titers of IgG, IgA and IgM anti
      P.brasiliensis antibodies and Western-blot for determining IgG, IgA and IgM
      antibodies against the antigen components of the fungus. Before treatment, 81.5%
      (Dot-blot) and 84% (ELISA) of the patients presented elevated IgG anti
      P.brasiliensis antibody titers which dropped slightly with treatment. On the
      other hand, the percentages of pre-treatment high-titered sera for IgA and IgM
      anti-P.brasiliensis were lower (51.9% and 51.8%: Dot-blot; 16.5 and 36%: ELISA,
      respectively) but the titers tended to become negative more frequently with
      treatment. Prior to treatment, the percentages of positivity for IgG, IgA and IgM
      anti-P.brasiliensis antibodies in Western-blot were 96%, 20.8% and 41.6%,
      respectively. Antigens with molecular weights varying from 16-78 kDa, from 21-76
      kDa and from 27-78 kDa were reactive for IgG, IgA and IgM antibodies,
      respectively. The most frequently reactive antigenic components had molecular
      weights of 27, 33 and 43 kDa for IgG, and 70 for IgA and IgM antibodies. During
      the period of study, the patients responded well to treatment. The present data
      confirm the diversity and complexity of the humoral response in PCM, and the
      importance of utilizing different serological tests to detect IgG, IgA and IgM
      anti-P. brasiliensis antibodies.

PMID- 9661306
TI  - Synanthropic rodent reservoirs of Trypanosoma (Schizotrypanum) cruzi in the
      valley of Caracas, Venezuela.
AB  - Direct blood examination and xenodiagnosis of 47 synanthropic rodents (Rattus
      rattus, R. norvegicus, Mus musculus) captured in the valley of Caracas,
      Venezuela, revealed trypanosomal infections in 12 R. rattus, 10 with T. lewisi
      and 2 with T. cruzi. Of the latter the course of parasitemia, the pleomorphism of
      the bloodstream trypomastigotes, tissue in naturally and experimentally infected
      rats and mice, host mortality, morphology of fecal parasites in Rhodnius prolixus
      used for xenodiagnosis, and infectivity of the bug feces for NMRI mice, were all
      characteristic of Trypanosoma (Schizotrypanum) cruzi. One rat, with a patent
      parasitemia, had numerous nests of amastigotes in cardiac muscle and moderate
      parasitism of the smooth muscle of the duodenum and of skeletal muscle. Mice
      inoculated with fecal flagellates from the bugs had moderate tissue tropism in
      the same organs and also in the colon and pancreas. The possible role of R.
      rattus in the establishment of foci of Chagas' disease in Caracas is discussed.

PMID- 9661305
TI  - Decay of antibody isotypes against early developmental stages of Schistosoma
      mansoni after treatment of schistosomiasis patients.
AB  - Antibodies to a number of parasite antigens are found in schistosomiasis
      patients, and antibodies to early developmental stages were demonstrated to be
      efficient immunologic markers for the diagnosis of schistosomiasis. In the
      present study, decay patterns of IgM and IgG antibodies against cercariae and
      schistosomula were investigated, in comparison to antibodies against worms and
      eggs in schistosomiasis patients after chemotherapy, for an investigation of
      seroepidemiologic aspects. Data obtained in the study of 359 serum samples from
      patients with Schistosoma mansoni infection, noninfected individuals, and
      patients followed-up for a period of 12 to 15 months after treatment provided the
      basis to postulate a general pattern for the kinetics of antibody decay. Before
      treatment, the antibody pattern was represented by a unimodal curve, which
      shifted to a bimodal curve after treatment, and ended with a unimodal curve
      similar to that for the noninfected group. Different types of antibodies were
      classified into four categories according to their decay features, and anti
      schistosomulum IgM was classified into the moderate-decay category, whereas other
      antibodies to early parasite stages were classified into the slow-decay category.
      The present methodology permits the identification of the most suitable
      antibodies to be detected in field control programs for schistosomiasis or other
      parasitoses.

PMID- 9661307
TI  - Trypanosoma cruzi: chemotherapy with benznidazole in mice inoculated with strains
      from Parana state and from different endemic areas of Brazil.
AB  - Strains of Trypanosoma cruzi from different geographical areas have shown
      different levels of susceptibility to trypanosomicidal drugs. The susceptibility
      in vivo to benznidazole was investigated in eighteen strains of T. cruzi. Twelve
      were isolated from chronic chagasic patients from different Chagas' disease
      endemic areas. The other six strains were isolated from the northwestern region
      of Parana state; two of them from patients, three from triatomines (Triatoma
      sordida) and one from wild reservoir (Didelphis sp.). To test drug the infected
      mice were divided into two groups of twenty. One group was treated with
      benznidazole for twenty consecutive days and the other group was used as
      untreated control. The treatment began after detection of the infection by direct
      blood examination or haemoculture. The control of cure was done through
      haemoculture and indirect immunofluorescence test. The drug eliminated the
      inflammatory lesions of the skeletal muscle of mice considered cured and from the
      heart of most of them. Moreover, the inflammatory lesions were reduced in treated
      but not cured animals. The T. cruzi strains studied showed a gradient of drug
      susceptibility that varied from 0% to 100%. Ten strains were considered sensitive
      to the treatment (61 to 100% of cure), one strain was partially sensitive (50% of
      cure) and seven strains were considered resistant to the treatment (0 to 40% of
      cure). This variation was observed both in strains of T. cruzi isolated from
      domestic and sylvatic cycles.

PMID- 9661308
TI  - Nickel contact dermatitis in Fortaleza, Ceara, Brazil (1993-1994).
AB  - This work consists in an evaluation of the occurrence of nickel contact
      dermatitis, its distribution between sexes and in which parts of the body the
      dermatitis usually occurs. It was accomplished a two year (1994-1995)
      retrospective study of 404 patch-tested patients which had previous clinical
      diagnosis of contact dermatitis. The occurrence of nickel sensitization was
      19.8%, 88.8% of these 19.8% were women and the rest, 11.2%, were men. The lesions
      were present predominantly on hands, forearms, earlobes and feet. The authors
      comment about possible variations of occurrence of nickel contact dermatitis in
      rural areas and/or tropical countries.

PMID- 9661309
TI  - Chronic pulmonary histoplasmosis in Brazil: report of two cases with cavitation
      diagnosed by transthoracic needle biopsy.
AB  - Two cases of Chronic Pulmonary Histoplasmosis are reported and other eleven
      cases, collected from Brazilian literature, are commented. After being clinically
      cured, one of our patients presented an Aspergillus fungus ball inside a
      cavitation in the wall of which H. capsulatum was disclosed. Comments are also
      done on the diagnosis of the mycosis.

PMID- 9661310
TI  - Coccidioidomycosis in Brazil. A case report.
AB  - Coccidioidomycosis is an endemic infection with a relatively limited geographic
      distribution: Mexico, Guatemala, Honduras, Colombia, Venezuela, Bolivia,
      Paraguay, Argentina and the southwest of the United States. In these countries,
      the endemic area is restricted to the semiarid desert like regions which are
      similar to the northeast of Brazil. CASE REPORT: The patient is a 32 year-old
      male, born in the state of Bahia (Northeast of Brazil) and has been living in Sao
      Paulo (Southeast) for 6 years. He was admitted at Hospital das Clinicas, at the
      Department of Pneumology in October 1996, with a 6 month history of progressive
      and productive cough, fever, malaise, chills, loss of weight, weakness and
      arthralgia in the small joints. Chest x-rays and computerized tomography
      disclosed an interstitial reticulonodular infiltrate with a cavity in the right
      upper lobe. The standard potassium hydroxide preparation of sputum and
      broncoalveolar lavage demonstrated the characteristic thickened wall spherules in
      various stages of development. Sabouraud dextrose agar, at 25 degrees C and 30
      degrees C showed growth of white and cottony aerial miceleium. The microscopic
      morphology disclosed branched hyphae characterized by thick walled, barrel shaped
      arthroconidia alternated with empty cells. The sorological studies with positive
      double immunodiffusion test, and also positive complement fixation test in 1/128
      dilution confirmed the diagnosis. The patient has been treated with ketoconazole
      and presents a favorable clinical and radiological evolution.

PMID- 9661311
TI  - Frequency and precocity of human intestinal parasitism in a group of infants from
      Rio de Janeiro, Brazil.

PMID- 9661312
TI  - Difficult patients: their construction in group therapy.
AB  - Written from the perspective of intersubjective theory, this article addresses
      how the leader and group members co-construct the difficult patient. Too often,
      therapists and patients have tended to attribute difficulties in therapy groups
      to "the difficult patient" without appreciating how they themselves contribute to
      the construction, the needs this construction serves, and the potential value of
      such patients to the group. Mistakes in group leadership, vicissitudes of
      intersubjectivity, disturbing intrapsychic defenses, and whole-group dynamics
      interact to produce the difficult patient. Also discussed is the group member who
      is difficult but who no longer meets the criteria for patienthood. By exploring
      the factors involved in the co-construction of the difficult patient, the authors
      hope to guide clinicians in the deconstruction of such impediments, thus allowing
      the difficult patient to become "just another group patient."

PMID- 9661313
TI  - An analytic group psychotherapy session: interpretations and hidden texts.
AB  - This article describes what happened with the participants and the group as a
      whole in an analytical group psychotherapy session. Our aim is to reveal how the
      particular session was run. We describe a period of resistance to change when the
      principal defences used were: somatization, acting-out, identification-with-the
      aggressor, and, more specifically, language abuse leading to confusion. We
      discuss the value of interpretations that are focused on the group as a whole,
      where the group is considered to be an internal object. Although this article is
      not exclusively about an object-relations model, we attempt to analyze the
      influence of projective identification, which has an effect on the therapist's
      task of recognizing his "container" and interpreting functions.

PMID- 9661314
TI  - Different patterns of change in narratives of men and women during analytical
      group psychotherapy.
AB  - Narratives of men and women concerning their interactions with other people were
      evaluated before and during analytically oriented group psychotherapy using the
      Core-Conflictual-Relationship-Theme (CCRT) method (Luborsky & Crits-Cristoph,
      1990). Relationship patterns of men and women developed differently during
      therapy. Some gender stereotypes persisted, others changed. During therapy the
      proportion of negative responses in the narratives increased in the men. Change
      in the narratives was not related to change in self-reported symptoms. For group
      treatments, the results suggest that the gender of the patients has to be taken
      into account. Knowledge of different developmental patterns for men and women in
      groups can be important in regard to the expectations of therapists and their
      countertransference.

PMID- 9661315
TI  - Conflict and aggression in group psychotherapy: a self psychological vantage
      point.
AB  - Self psychology's emphasis on listening and understanding from a patient's
      vantage point has led to a commonly held misconception that it ignores conflict
      and aggression; this is not the case. On the contrary, an understanding of rage
      is central to Kohut's views. Some basic self psychological concepts and their
      application to dealing with conflict and aggression in group psychotherapy are
      presented along with a clinical illustration. In the approach presented, it is
      not the rage and conflict itself that becomes the focus of the therapeutic
      endeavor. It is the underlying vulnerability that must be expressed, explored,
      and worked through in order to facilitate a curative process.

PMID- 9661316
TI  - A simulation model for training in group process.

PMID- 9661317
TI  - Gastrointestinal allergy to food: a review.
AB  - Gastrointestinal food allergy still poses a challenge to the clinician because of
      its variable symptomatology and lack of reliable diagnostic tests. Its prevalence
      is estimated at 2 approximately 5%, higher in children than in older age-groups.
      Allergy to food usually diminishes with advancing age. Although a wide variety of
      foods can cause allergic reactions, cow's milk is the most common cause of food
      allergy in infants and young children. Depending upon the speed of onset of
      symptoms, immediate and delayed types of food allergy have been described.
      Gastrointestinal symptoms in food allergy have been explained by alterations in
      transport across the intestinal wall (increased secretory and/or decreased
      absorptive functions), increased permeability, and motility of the intestine. The
      exact pathogenesis of food allergy is still not clear. However, immediate type of
      food allergy is believed to be mediated by type I hypersensitivity reaction,
      involving mast cells and food-specific IgE antibodies. The diagnosis of food
      allergy is based upon a favorable response to an elimination diet and a response
      to a challenge with the suspected food. The condition is treated by eliminating
      the allergenic food from diet for as long as 9-12 months in case of cow's milk
      allergy. While exclusive breast-feeding for the initial four months or more
      reduces the chances of development of food allergy, the role of diet restrictions
      in the mother in reducing the incidence of food allergy in the infant is
      controversial. Data on food allergy from developing countries are limited. This
      may be due to lack of diagnosis or less attention given to the condition relative
      to other diseases including infectious diarrheas and acute respiratory
      infections. The role of cow's milk allergy in the pathogenesis of persistent
      diarrhoea, a major problem in the developing world, remains speculative. Frequent
      intestinal infections and reduced secretory IgA, which are associated with
      malnutrition, alter intestinal permeability and result in an increased uptake of
      food antigens. The increased antigenic load combined with factors such as an
      atopic predisposition may initiate an abnormal mucosal immune response resulting
      in chronic enteropathy.

PMID- 9661318
TI  - The acute infectious diarrhoeas as diseases of the intestinal mucosa.
AB  - One of the intriguing aspects of the acute infectious diarrhoeas is that, while
      resulting from an infection of the intestinal tract, they only last from a few
      hours to a few days. The study of the interactions between infectious agents and
      intestinal epithelium has allowed a better understanding of the cellular and
      molecular mechanisms that cause the sudden loss of water and electrolytes, the
      hallmark of acute diarrhoea. These interactions have also led to formulating oral
      rehydration solutions used worldwide now. They do not, however, allow
      understanding the short course of most intestinal infections. For that, one has
      to consider the intestinal epithelium as part of an anatomical and functional
      system that, including the many types of cells present in the lamina propria,
      constitutes the intestinal mucosa. Infectious agents interact with the whole of
      the mucosa, including the cells of the lamina propria. This leads, among other
      things, to a change in the functions of the epithelial cells and accelerates
      their turnover. The pathophysiology of the intestinal mucosa leads to better
      understand the short and benign course of most intestinal infections. It also
      leads to better understand the physiology of the intestinal mucosa, and the
      interactions between the body and its nutritional environment.

PMID- 9661319
TI  - Caretakers' knowledge and preparation abilities of salt-sugar solution in north
      eastern Nigeria.
AB  - Awareness and knowledge of oral rehydration therapy (ORT) and preparation
      abilities of salt-sugar solution (SSS) were investigated by means of focus group
      discussions and complemented by a structured questionnaire survey of mothers in
      rural and urban areas of north-eastern Nigeria. ORT awareness was high with some
      intra-regional variations. Perception of ORT function was, however, grossly
      unrealistic, with a third to four-fifth of mothers expecting ORT to stop
      diarrhoea. At least one quarter of mothers lacked adequate SSS preparation
      abilities and the materials and ingredients required for its preparation. Re
      evaluation of the content and method of imparting health education messages in
      ORT promotion is recommended. Such messages should emphasise the function of ORT.
      It is also recommended that standardised cups for water, salt and sugar
      measurements be provided to households as a ready means of ensuring the correct
      preparation of SSS in the home-based management of diarrhoea.

PMID- 9661320
TI  - Enteric bacterial pathogens in stools of residents of urban and rural regions in
      Nigeria: a comparison of patients with and without diarrhoea and controls without
      diarrhoea.
AB  - A total of 2,400 stool samples comprising 1,200 from patients with diarrhoea (600
      each from urban and rural area) and 1,200 similarly divided controls were
      obtained from school children and clinic attendants of government and private
      clinics around three designated study centres of Edo, Lagos and Cross River
      states, Nigeria. These were screened for the prevalence of bacteria that could
      cause diarrhoea. Diarrhoea cases in urban areas had a high prevalence rate for
      Campylobacter spp. (28%), followed by enteropathogenic Escherichia coli (22%),
      Salmonella spp. (17%), Shigella spp. (14%), Aeromonas spp. (5%), and Yersinia
      enterocolitica (4%), whereas in rural areas E. coli was the most frequently
      encountered pathogen (18%), followed by Salmonella spp. (16%), Aeromonas spp.
      (15%), Shigella spp. (9%), Campylobacter spp. (8%), and Plesiomonas shigelloides
      (8%). A similar distribution but with lower rates was noted for controls in both
      urban and rural areas, however, no P. shigelloides was isolated. Results
      highlight a possible difference between the prevalence of enteric bacteria in
      rural and urban areas and reveals the strong association of Aeromonas and
      Plesiomonas species with cases of diarrhoea in Nigeria.

PMID- 9661321
TI  - Mechanism of purgative effect of magnesium sulphate on mouse colon.

PMID- 9661322
TI  - Comparison of main features in children with cholera O1 and O139 in Yangon,
      Myanmar, 1996.

PMID- 9661323
TI  - Glucose-based and rice-based ORS.

PMID- 9661324
TI  - Bibliography on diarrhoeal diseases.

PMID- 9661325
TI  - Should perinatal nurses be required to complete an advanced cardiac life support
      (ACLS) course?

PMID- 9661326
TI  - The lived experience of women who undergo prenatal diagnostic testing due to
      elevated maternal serum alpha-fetoprotein screening.
AB  - PURPOSE: To explore the lived experiences of a sample of 16 pregnant women who
      obtained an elevated maternal serum alpha-fetoprotein screening and had further
      prenatal diagnostic procedures to determine fetal status. DESIGN: Phenomenology
      METHODS: Sixteen pregnant women were interviewed on two occasions, immediately
      after contact with a maternal-fetal medicine specialist, and again during the
      immediate postpartum period. Interviews were conducted until analysis indicated
      that there was emergence of common themes. A nine-step method was used in the
      analysis procedure. RESULTS: The exhaustive description of the experience
      revealed four chronological reaction periods during the experience. CLINICAL
      IMPLICATIONS: Interactions clearly demonstrated the need for nursing
      interventions throughout the experience of prenatal diagnostic testing.

PMID- 9661327
TI  - School-based intervention to promote coping in rural teens.
AB  - PURPOSE: To evaluate a program designed to help high school students with
      depressive symptomology to effectively cope. DESIGN: Two-phase experimental
      study. METHODS: Rural high school students (N = 222), ages 14 through 19 years,
      were surveyed to identify teens with depressive symptomatology, identify
      stressful life events and coping styles of at-risk subjects, and evaluate a
      cognitive-behavioral group intervention to enhance students' coping and affect
      levels of depression. Students with depressive symptomatology were randomized
      into control (n = 18) or intervention (n = 23) groups. Intervention subjects were
      treated with a nurse-led, 8-week cognitive skills group, conducted at school.
      RESULTS: On posttesting, the intervention groups demonstrated reduced depressive
      symptoms in females and a wider range of coping compared with controls. CLINICAL
      IMPLICATIONS: School-based nurses are in an ideal position to provide assessment,
      referral, and intervention programs in the natural setting of the school. Results
      of this study indicate that such programs can be implemented successfully in
      schools and have the potential to promote mental health in teenagers.

PMID- 9661328
TI  - Guiding mothers of high-risk infants in obtaining social support.
AB  - The purpose of this article is to describe how nurses can assist the new mother
      of a high-risk infant, especially a preterm infant, in identifying and obtaining
      the social support needed to help the family adapt in the first few weeks after
      the birth. The interventions recommended are based on a research study conducted
      by the authors and colleagues and summarized within this article. Because support
      was more important than these mothers expected it to be, it is important that
      nurses in prenatal, postpartum, neonatal, home health, and extended care settings
      recognize the need to assist women in identifying their support needs. In
      addition, nurses can help the mothers identify individuals within their social
      network who could assist them with those needs. Meeting the social support needs
      of a mother is important for her own mental and physical health and well-being.
      It also helps her meet the social and developmental needs of her infant.

PMID- 9661329
TI  - Reducing preterm and low birthweight births: still a nursing challenge.
AB  - Preterm birth and low birthweight are correlated with much of the infant death
      seen in the United States. Despite 15 years of research, both preterm birth rates
      and low birthweight rates continue to increase. This article describes what is
      known about the prevention of preterm birth and low birthweight, and offers
      advice to nurses for nursing interventions that could prove effective in
      preventing such tragedies in the future.

PMID- 9661330
TI  - Caring and healing in the 21st century.
AB  - As the 21st century approaches, nurses must be prepared to offer new treatment
      methods when caring for children. The purpose of this article is to familiarize
      nurses with human caring theory and complementary and alternative medicine, and
      to offer a practical way of integrating these methods into nursing care. Nurses
      can learn to choose simple, conservative, noninvasive, nonintrusive healing
      methods that are met with little resistance by other health care professionals.
      Clinical implications of the Nurse's Tool Box suggest methods such as drawing,
      acupressure, guided imagery, storytelling, therapeutic touch, soft music, and
      humor as ways to help children heal. By tapping into certain frequency currents
      through the use of these tools, nurses may build, repattern, or facilitate human
      energies to replenish children's minds, bodies, and souls, creating wholeness and
      harmony. By understanding human caring theory and complementary and alternative
      medicine, and by using a practical approach to healing, nurses in the new century
      can mend children in ways they never have before.

PMID- 9661331
TI  - Emerging drug resistance.

PMID- 9661332
TI  - Nursing research in today's downsized, short-staffed environment.

PMID- 9661333
TI  - The birth ball--are you using it in your practice setting?

PMID- 9661334
TI  - Severely impaired children: questions of ethics.

PMID- 9661336
TI  - Preventing abuse during pregnancy.

PMID- 9661335
TI  - Bed rest in complicated pregnancy.

PMID- 9661337
TI  - Gender differences in motivational style: a comparison of measures and curriculum
      area.
AB  - BACKGROUND: Gender has long been implicated in school-based performance with
      gender differences varying across curriculum domains. Motivational differences
      have often been cited as a possible cause. However, evidence for the pattern of
      motivational difference between the genders is unclear. AIMS: This study compares
      the motivational responses of girls and boys in the curriculum areas of
      mathematics and English. Two different measures of motivation are employed.
      SAMPLES: The sample consists of all pupils from years 7, 9 and 11 in two
      secondary schools in Northern England. A total of 435 yr 7, 389 yr 9 and 357 yr
      11 students was available. METHODS: Students completed two assessments of
      motivation, one based on self-report measures of goal strength and the other on
      performance over four tasks. Some school performance data were also available.
      RESULTS: The two motivation measures produce different patterns of results. The
      task-based measure shows no gender based differences while the other indicates a
      pattern of differences broadly suggestive of an advantage for girls. CONCLUSIONS:
      Future exploration of gender effects in motivation needs to give careful
      consideration to the type of motivation under consideration. Univariate models
      are unlikely to be adequate.

PMID- 9661338
TI  - The implications for academic attainment of perceived gender-appropriateness upon
      spatial task performance.
AB  - BACKGROUND: Male superiority in spatial ability has traditionally been used as an
      explanation for the male domination of 'spatial' disciplines such as mathematics,
      science and computing. Data are presented which show the degree of male
      domination of these disciplines at a range of academic levels. AIMS: To evaluate
      the effect of describing a spatial ability test either as a measure of spatial
      ability (traditional format) or as a measure of empathy, upon male and female
      performance. Psychological gender is also assessed to evaluate the role of
      masculinity and femininity upon performance. METHOD: Eighty-four sixth form
      students were presented with the Group Embedded Figures Test in the assessment's
      traditional format and as a measure of 'empathy'. Levels of masculinity and
      femininity were also assessed using the Bem Sex Role Inventory. RESULTS: Whilst
      the description of the nature of the assessment did not affect male performance,
      female performance' varied significantly as a function of test description.
      Females only underperformed when the test was described as a measure of spatial
      ability. Additionally, those high in masculinity were found to outperform those
      high in femininity. CONCLUSIONS: The results suggest that 'apparent' sex
      differences in spatial ability are more accurately described as psychological
      gender differences which determine the motivation to attempt the assessments.
      COMMENT: The implications for genderised activities (such as computing) within
      education are discussed.

PMID- 9661339
TI  - Teachers as significant others: gender differences in secondary school pupils'
      perceptions.
AB  - BACKGROUND: Numerous studies refer to the impact of parents and friends as
      significant others for adolescents. Given the unique nature of the relationships
      between teachers and their pupils and their intensive everyday interactions, the
      present study focuses on a not yet covered topic, namely the meanings that
      adolescents attach to the significance of their teachers. AIMS: This study was
      aimed at examining gender differences in secondary school pupils' perceptions
      regarding positive and negative aspects of the significance of their teachers,
      and to investigate the possible different domains in which teachers as compared
      with parents and friends might be significant for the adolescents. SAMPLES: A
      total of 297 Israeli secondary school pupils (approximately 57 per cent girls and
      43 per cent boys) studying in 12 tenth grade classes (age modal 16) participated
      in this study. METHODS: A questionnaire dealing with pupils' perceptions of
      significant teachers was administered. Pupils were asked to indicate the extent
      to which significant teachers are characterised by various descriptors (it was
      defined for the pupils that a significant teacher is one whom the pupil perceives
      as having an important influence on her/him). In addition pupils were asked to
      answer two open-ended questions regarding the domains in which teachers, as
      compared to their parents and their friends, might be significant for them.
      RESULTS: Findings showed that the most frequently mentioned characteristics of
      significant teachers were: teachers who 'take pupils seriously', 'have confidence
      in them', 'make it easier for them to understand things' and 'push them to do
      well'. It was also found that girls, more than boys, characterise significant
      teachers as facilitating learning and relationships; and that boys, more than
      girls, perceive significant teachers as obstructing their personal development.
      CONCLUSIONS: Our findings allude to the high potential that teachers may have for
      impact on their pupils, beyond the domain of learning alone, and provide support
      for the existence of differential perceptions of significant teachers among boys
      and girls. These gender differences were explained in terms of the different
      character of teachers' interaction with the two sexes, and the fact that in the
      Israeli educational system more than 80 per cent of the teaching staff are women.

PMID- 9661340
TI  - Scottish and Australian teacher stress and strain: a comparative study.
AB  - BACKGROUND: There is a widespread belief that teacher stress is a serious problem
      with obvious implications for teachers' physical and psychological health status
      as well as performance. There is much published research about teacher stress,
      although not about cultural or national group comparisons. AIM: This study
      examines the occupational stress, strain and personal coping resources of a
      comparative group of Scottish and Australian vocational teachers. SAMPLE: Three
      hundred and thirty two Scottish and Australian vocational and further education
      teachers. METHOD: A standardised test, the Occupational Stress Inventory, was
      used to gather the data. RESULTS AND CONCLUSIONS: Overall it was found that
      stress and strain similarities between the two national groups far outweighed the
      differences. For instance, there were no between-group differences in strain
      levels, which were found to be at 'average' levels for both groups. Nevertheless,
      for both groups of teachers, role overload appeared to be a strong source of
      occupational stress.

PMID- 9661341
TI  - Crisis in London's in-patient mental health services.

PMID- 9661342
TI  - Signposts for success for learning disability services.

PMID- 9661343
TI  - New approaches to the treatment of venous leg ulcers.
AB  - Increased understanding of the pathology of leg ulcers has made the differences
      in the pathologies of leg ulcers between patients more apparent. This article
      examines some areas of research that are advancing our understanding of the
      pathology of venous leg ulcers. The impact that this information is having on the
      development of new therapies and the implications for nursing practice are
      discussed.

PMID- 9661344
TI  - Cancer of the prostate. 2. The nursing role in health promotion.
AB  - The first article (Vol 7(3): 152-8) in this three-part series presented the
      incidence of prostatic cancer and discussed the importance of diagnosis, early
      detection and screening. This article examines assessment and staging of local
      disease and the sites of metastatic spread. The nurse's role in promoting men's
      health is also highlighted. Health education models and the choice of an
      appropriate one are discussed, emphasizing the role of the nurse. Finally,
      recommendations for practice are offered.

PMID- 9661345
TI  - Integrated care management.
AB  - Some clinicians are at the leading edge of good practice in the introduction of
      integrated care management (ICM) (Wilson, 1996) based on partnership, quality and
      driven by performance. The new Government White Paper (Department of Health,
      1997) outlines proposals for integrated care with all care planners and providers
      working collaboratively. A number of health and social care organizations have
      worked collaboratively to develop care programmes based on patient-centred care.
      One of the vehicles is multidisciplinary pathways of care (MPCs) which is the
      risk management tool for monitoring jointly agreed quality and patient outcome
      criteria from the performance of planning and providing individual patient care.
      ICM views the multidisciplinary approaches to collaborating care delivery by
      activity, cost and quality, and using a process approach to problem- and outcome
      based care delivery. Involving patients and their carers in determining the
      process and outcomes of care provides a route to better communication, patient
      and staff satisfaction and the overall quality of care. This article deals with
      the use of ICM through the monitoring system of multidisciplinary pathways of
      care (MPCs) as a tool for minimizing risk and improving the continuous quality
      improvement of patient care. MPCs are one of the components of ICM which need to
      incorporate clinical guidelines, protocols, interdisciplinary standards,
      evidenced-based practice and clinical outcomes which are continuously monitored
      across all sectors of care.

PMID- 9661346
TI  - Exploring mutuality within the nurse-patient relationship.
AB  - This article explores the concept of boundaries within the nurse-patient
      relationship. Drawing on child development theories the authors explore the
      difficulties of boundary maintenance and link this to the professional aspects of
      therapeutic alliance. The ability to establish clear boundaries between ourselves
      and others is closely related to the capacity to function as a healthy adult and
      as such may be said to play an important role in the development of mental health
      difficulties. However, it is generally accepted by psychological theorists that a
      certain amount of projection and transference are likely to occur in every two
      person relationship and as a result boundary confusion is likely to be
      experienced by both parties to a greater or lesser extent in the nurse-patient
      relationship. If, as is currently asserted by the nursing profession, the nurse
      patient relationship is based on the principle of equality then it follows that
      both the nurse and the patient carry equal responsibility for maintaining the
      boundaries within which their interactions take place. The authors argue that it
      may be more appropriate to think in terms of a relationship founded on the
      concept of 'mutuality'. Such a position enables the concept of therapeutic
      reciprocity to be embraced alongside the reality that ultimately it is the nurse
      who carries the responsibility for 'holding' the boundaries within which the
      relationship is 'acted out.'

PMID- 9661347
TI  - Clinical assessment for post-traumatic stress disorder.
AB  - Post-traumatic stress disorder (PTSD) is an increasingly fashionable diagnosis
      used to describe an individual who experiences psychological problems following
      his/her involvement in a traumatic event. However, PTSD can prove difficult to
      assess accurately owing to the unique problems of co-morbidity with other
      psychological disorders or the late onset of symptoms. Paradoxically, PTSD may be
      misdiagnosed by a healthcare professional which may result in inappropriate
      therapeutic intervention. This article introduces a simple five-stage assessment
      that is designed to help the clinician determine whether the client's distress is
      caused by PTSD or another disorder. These guidelines are structured and explore
      the five stages of PTSD assessment: collecting background information; initial
      contact with the client; correctly identifying the problem; general assessment;
      and summary. Finally, some recommended structured clinical assessment guidelines
      and psychometric rating scales are outlined.

PMID- 9661348
TI  - Cardiac rehabilitation following myocardial infarction.
AB  - Coronary heart disease is the major cause of death in the UK, but cardiac
      rehabilitation programmes have tended to develop in an ad hoc and unsystematic
      way. This article considers some of the deficits in current practice and suggests
      ways in which nurses can contribute more fully to care in this area. The need for
      better training and the necessity to develop skills in psychological care are
      highlighted. The authors also emphasize the importance of giving greater
      attention to a number of areas such as family involvement, sexuality and gender
      issues, and community follow-up.

PMID- 9661349
TI  - Nurse occupational stress research. 6: Methodological approaches.
AB  - This article, the final in the series on nurse occupational stress, reviews the
      most common methodological approaches used to study nurse stress. It also
      discusses the methods that are rarely used and alternative methods that have not
      previously been used to research nurse stress. The strengths and limitations of
      the different approaches are examined.

PMID- 9661350
TI  - Is the heyday of the hospital finally over?

PMID- 9661351
TI  - Government launches new recruitment campaign.

PMID- 9661352
TI  - How can nurses avoid negligence claims?

PMID- 9661353
TI  - A review of the development of isolation precautions.
AB  - Isolation precautions are crucial to the effective control of infection in
      healthcare settings. Isolation practices have developed considerably over the
      last 150 years; current systems and procedures of isolation are rational and
      scientifically-based. Epidemiological patterns of various diseases develop and
      change and isolation precautions aim to prevent their spread. Many historical
      developments originated in America, at the Centre for Disease Control (CDC).
      Isolation techniques and the more recent two-tier system of isolation were among
      these developments. This article reviews the development of various isolation
      precautions and examines the impact of CDC recommendations on UK practice.

PMID- 9661354
TI  - Stoma care: exploring the value of effective listening.
AB  - This article discusses how nurses can effectively utilize listening skills during
      interactions with patients. Listening is a core skill for all healthcare
      professionals with studies demonstrating that nurses perceive themselves to be
      much less skillful in the use of facilitative interpersonal skills which involve
      listening than practitioner centred authoritative ones. Listening effectively
      allows nurses to respond more completely to patients' needs but there are many
      obstacles which unfortunately can interfere with this process. Stoma care nurses
      utilize listening skills to ensure that both the physical and psychological needs
      of their patients are met. The author suggests that listening skills can enhance
      intuitive nursing practice.

PMID- 9661355
TI  - Stroke. 1: A paradigm case in nursing rehabilitation.
AB  - This is the first of two articles which consider rehabilitation following a
      stroke. Although stroke is a major cause of morbidity and mortality in the UK
      there have been relatively few studies describing its long-term effects. Despite
      relatively good functional recovery, in many cases a number of stroke survivors
      still experience 'long-term misery'. This article argues for an expanded range of
      outcomes in stroke rehabilitation and for greater attention to be paid to the
      psychological needs of stroke survivors and their carers. Areas of deficit in
      stroke rehabilitation are described, as is the currently poorly developed nursing
      role.

PMID- 9661356
TI  - Nursing management of skin grafts and donor sites.
AB  - Skin grafting is one of the most commonly used techniques in plastic and
      reconstructive surgery. The patient undergoing split-thickness skin grafting may
      pose a variety of wound care problems for the nurse. The issues that may need to
      be addressed include: the reasons for grafting; type of graft used; preoperative
      and postoperative care of the recipient and donor sites; and the provision of
      general measures required to promote wound healing and successful graft take for
      the patient.

PMID- 9661357
TI  - How do I diagnose and treat wound infection?

PMID- 9661358
TI  - Compression therapy for lymphoedema from Vernon-Carus.
AB  - Lymphoedema is a chronic condition which, if untreated, becomes progressively
      worse. It cannot be cured, but it can be monitored, treated and maintained to
      give the patient a relatively normal quality of life (Barrett, 1997). This
      product focus looks at lymphoedema, its treatment and the role of a compression
      system from Vernon-Carus.

PMID- 9661360
TI  - Complaints within the NHS.

PMID- 9661359
TI  - An alternative training approach to clinical supervision: 2.
AB  - In this, the second of two articles focusing on the issue of training in clinical
      supervision, the alleged benefits of training students to be supervisees is
      highlighted. These are: a substantial reduction in training costs and time; a
      possible standardization of training; the creation of greater equality and
      intentionality in the working alliance; an increased student awareness and
      understanding that supervision is for their benefit; the sharing of values,
      ground rules, terms and aims between the supervisee/supervisor and the
      organization; a sense of comradeship between peers in a culture that is often
      described as having a sense of divide and rule; and a greater sense of team
      cohesion. The development of basic intrapersonal skills (e.g. reflecting on
      practice, choosing issues, asking for and using help appropriately) in a non
      threatening forum is also of great benefit. The authors conclude that an
      educational model would include both theoretical and experimential components
      with the theory preceding the clinical supervision experience. Evaluation of this
      training could be carried out using a methodology similar to that used by
      Butterworth et al (1997) in evaluating the impact of receiving supervision.

PMID- 9661361
TI  - Nursing professionalism: is it decreasing?

PMID- 9661362
TI  - Our heritage: a history of gastroenterology and gastroenterology nursing.
AB  - Gastroenterology is a relatively new specialty but has roots dating back to 1868.
      Gabriella and Rudolph Schindler pioneered humane methods of performing
      gastroscopies with a semiflexible gastroscope that are still used today,
      including numbing of the throat, instruction about the examination to encourage
      cooperation, and spoken guidance and encouragement during the procedure. This
      history is presented to demonstrate the creativity and dedication of the founders
      of gastroenterology.

PMID- 9661363
TI  - The gastric bubble: medicine, magic or mania?
AB  - This paper is presented to acquaint the GIA with a new medical procedure that is
      rapidly gaining popularity throughout the United States. It includes a brief
      discussion of the medical device itself and the technique of implantation as well
      as indications and contraindications for its use. In addition, an overview of the
      program developed at Placentia-Linda Community Hospital, Placentia, CA, is
      offered. Personal reflections are also rendered regarding the unique nursing
      opportunities afforded by this procedure and its accompanying follow-up program.
      In conclusion, this paper will substantiate, with personal experience and early
      supportive research data, the parallels between the medicinal value, the magic,
      and the mania accompanying the Gastric Bubble.

PMID- 9661364
TI  - The structure and function of endoscope channels: the inside story.
AB  - The GIA who has knowledge of channels in the flexible endoscope can avoid the
      need for repairs due to channel blockage and will be able to achieve the best
      possible instrument care. This paper provides a detailed description of the
      channels of the working endoscope, including location, access and functional
      interrelation-ships, to help make cleaning, disinfecting and troubleshooting a
      logical process. Diagrams are included to clarify the descriptions.

PMID- 9661365
TI  - Women with gastrointestinal symptoms: implications for nursing research and
      practice.
AB  - Irritable bowel syndrome and functional bowel disorder are diagnoses used to
      describe chronic GI symptoms for which no overt pathological condition can be
      identified. Symptoms are more common in women and are frequently followed in
      gastroenterology clinics. The purpose of this article is to provide an overview
      of the research linking GI symptoms and reproductive cycling and to discuss
      implications for practice. GIGl symptoms such as stomach pain and nausea are
      highest during menses compared with other cycle phases; also, stool consistency
      is loosest at menses. This pattern is present in control subjects. In women with
      irritable bowel syndrome the same pattern is seen but with higher symptom
      intensity. Although animal studies have demonstrated that estrogen and
      progesterone modulate contractile function of some GI segments. In humans,
      symptoms are highest when these hormones are at the lowest levels. Thus, symptoms
      in women may be related to decreasing ovarian hormone levels or to other
      circulating hormones or factors which vary with the menstrual cycle.
      Additionally, other factors such as stress aggravate symptoms. Therapeutics
      directed toward increasing patient awareness of cyclic patterns in symptom
      complaints, for example, via the use of daily symptom diaries may be a useful
      adjunct to dietary, pharmacological, and other therapies.

PMID- 9661366
TI  - A new approach to assessment and documentation of conscious sedation during
      endoscopic examinations.
AB  - Assessment and documentation of patient responses to treatment and/or invasive
      procedures are important facets of nursing care. The purpose of this article is
      to describe a tool for assessing and quantifying a patient's response to sedation
      and tolerance of a specific diagnostic and/or therapeutic procedure. Use of the
      conscious sedation scale will allow the nurse to objectively measure the
      patient's outcome. This tool will also facilitate better patient care and
      documentation and substantiate nursing intervention.

PMID- 9661367
TI  - Leadership: charting the course for health care.

PMID- 9661368
TI  - A watchword for nursing: discovery.

PMID- 9661369
TI  - Learning the ropes.

PMID- 9661370
TI  - Nursing, politics, and you.

PMID- 9661371
TI  - Tips on grassroots organizing.

PMID- 9661372
TI  - A lesson in dying.

PMID- 9661373
TI  - Being restrained: a study of power and powerlessness.
AB  - Previous research about the use of restraints has mainly sought generalizations
      regarding (a) who is likely to be restrained, (b) the frequency of the use of
      restraints, and (c) the behavior that precipitates the application of restraining
      devices. Therefore, there has been a paucity of research that attempts to
      understand the impact of restraint on the restrained person. The purpose of this
      study was to understand the meaning of the experience of being restrained for 10
      psychiatric patients who had been restrained in leather restraints. Participants
      were interviewed in unstructured interviews. The taped interviews were
      transcribed and analyzed by means of a modification of an eight-stage
      interpretive process, grounded in Heideggerian phenomenology. In this article the
      theme of power is reported and discussed.

PMID- 9661374
TI  - Stress, health, and depressive symptoms in older adults at three time points over
      18 months.
AB  - This descriptive study is a secondary analysis of data that examined depressive
      symptoms in a random sample of 429 community-dwelling adults aged 65 years and
      older. Participants were classified as having consistently high (n = 20).
      consistently low (n = 327), or fluctuating (n = 82) levels of depressive
      symptoms, based on scores from the Center for Epidemiological Studies-Depression
      Scale (CES-D; L. S. Radloff, 1977) at three time points over the course of 18
      months. Differences in stress (life events and daily hassles), health (self
      assessed health and physical complaints), and biographic variables among the 3
      groups were examined. One quarter of the sample reported high depressive symptoms
      at least once over 18 months. There were significant differences among the 3
      symptom groups on each of the stress and health measures and on marital status.
      The findings support the relationship among stress, health, and depressive
      symptoms over time. Implications for clinicians and researchers are discussed.

PMID- 9661375
TI  - Underutilization of mental health services by Asian-Americans residing in the
      United States.
AB  - Asian-Americans are the fastest-growing minority in the United States, and they
      are a culturally diverse group. Knowledge about this growing minority population
      is important for the purposes of planning appropriate mental health care. Asian
      Americans living in the United States rarely use mental health services. The
      reasons for this, along with suggestions for developing more culturally sensitive
      mental health services, are presented. A model for cultural competence can
      provide a framework for psychiatric nurses and other mental health professionals
      (MHPs) to become more aware of Asian-American values and beliefs and provide more
      culturally sensitive care. Awareness tools are included to guide MHPs in
      determining whether culturally competent care is available locally to meet the
      needs of this underserved population.

PMID- 9661376
TI  - Assessment of quality of life indicators among selected patients in a community
      cancer center.
AB  - Quality of life and outcome assessments are particularly critical for nurses in
      assessing clinical care for diseases such as cancer because of potential
      mortality and the exacting modalities of treatment. The 278 study participants
      were patients at the M.D. Anderson Cancer Center Orlando. The respondents were
      assessed with the Health Status Questionnaire (HSQ; D. M. Radosevich, H. Wetzler,
      & S. M. Wilson, 1995). Prostate cancer patients scored higher (had a higher
      quality of life) on average (6.08%) than breast cancer patients on all subscales
      except Physical Functioning. The diagnostic center patients scored higher (9.68%)
      than breast cancer patients and prostate cancer patients (3.47%). Breast cancer
      respondents scored 16.61% lower than the normative values for individuals less
      than 65 years of age, whereas prostate cancer respondents scored 10.91% higher
      than the normative values for those older than 65. The data analysis confirmed
      that breast cancer and prostate cancer patients have statistically different
      scores on the HSQ, implying different quality of life concerns for each group.

PMID- 9661377
TI  - An analysis of research on religious and spiritual variables in three major
      mental health nursing journals, 1991-1995.
AB  - A review of quantitative research studies published between 1991 and 1995 in 3
      major mental health nursing journals revealed that approximately 10% (31 of 311)
      included a measure of religion or spirituality. This percentage (10%) is 3 to 8
      times higher than that found in previous reviews of empirical research in
      psychological and psychiatric journals, suggesting that mental health nursing
      research is more sensitive to the role of religious-spiritual factors on mental
      health than research in related disciplines. The results are discussed in the
      context of the history and philosophy of nursing and in comparison to related
      disciplines. Methodological aspects of the research, especially the importance of
      multiple measures, are discussed, as are other salient findings.

PMID- 9661378
TI  - Staff assaults and injuries in a psychiatric hospital as a function of three
      attitudinal variables.
AB  - Although the available research makes reference to the connection between staff
      attitudes and patient assault, solid evidence of the connection is lacking. This
      investigation sought to examine 3 attitudinal variables that in the literature
      seemed to have the strongest relation to staff assaults and injuries. External
      locus of control, anxiety, and authoritarianism on the part of staff were
      examined in relation to the experience of assaults and injuries. A sample of 78
      staff members working at a psychiatric hospital responded to a survey; results
      indicated an associative relationship between both a more external locus of
      control and high trait anxiety and employees' experience of work-related
      injuries. Associations also were noted between both locus of control and
      authoritarianism and employees' frequency of assault and injury experiences. The
      findings provide important information that suggests that locus of control,
      authoritarianism, and trait anxiety on the part of staff members are connected
      with patient assaults and injuries.

PMID- 9661379
TI  - Crib sheets or security blankets?
AB  - This article describes the sanctioned use of crib sheets as a nursing
      intervention to decrease test anxiety when the classroom is the practice setting
      for psychiatric/mental health nursing faculty. The products that the students
      created offered additional unsuspected benefits. The faculty were convinced that
      the use of crib sheets can be a sound intervention to reduce students' test
      taking anxiety.

PMID- 9661380
TI  - May 1998 developing nursing practice.

PMID- 9661381
TI  - Some issues in the assessment of clinical practice: a review of the literature.
AB  - This paper focuses on some issues in the assessment of clinical practice of
      particular interest to the author. The assessment of students of nursing in
      clinical practice is acknowledged as a long-standing and difficult problem. There
      is little consensus as to what is meant by the term competence when applied to
      clinical nursing practice, making the assessment of clinical practice a mainly
      subjective process. The English National Board (1989) has distinguished the term
      mentor as meaning counsellor and guide, nevertheless the roles of mentor and
      assessor are frequently confused. It is suggested that nurses are equally
      accountable for the accurate assessment of student nurses' clinical skills as
      they are for their own practice. The validity and reliability of tools used to
      assess clinical practice are difficult to establish, making objective assessment
      complex at best, and impossible at worst. The assessment of the reflective
      process has been suggested as one way out of the dilemma, but the ability to
      think and to write does not necessarily translate into competent clinical
      practice.

PMID- 9661382
TI  - Nursing practice draws upon several different ways of knowing.
AB  - This paper explores the proposition that nursing practice draws upon several
      different ways of knowing. It highlights difficulties often faced by practising
      nurses in defining what they do and hence what it is that constitutes nursing
      practice. Following formal definition and analysis of sources of literature
      regarding nursing knowledge, issues such as the origins of knowledge and the
      sources of nursing knowledge are addressed. The types of knowledge required to
      enhance nursing practice are discussed, focusing upon future opportunities and
      innovations in the generation of knowledge for nursing. Finally, recommendations
      are made regarding the way forward for nurses endeavouring to communicate the
      complexities of nursing practice.

PMID- 9661383
TI  - Nursing development units: their structure and orientation.
AB  - This paper provides background material about the Department of Health funded
      Nursing Development Units (NDUs), specifically their biographical and contextual
      characteristics, their aims and values, and their organization of work and
      resources acquired. The data were drawn from questionnaires to clinical leaders
      and from documentation. The findings are summarized under five questions which
      address the NDUs' values and aims, their organization of work, multiprofessional
      working, activeness in acquiring resources and support and the effect of the host
      organization. Taken as a whole, the aims match the vision of the ideal NDU
      specified by the pioneers of the NDU movement, and most clinical leaders
      subscribed to primary nursing as their preferred mode of organizing nursing work.
      Multiprofessional working was a common feature and there was considerable
      evidence of equality in team membership status. A small number of NDUs had been
      awarded grants for research and most were successful in generating income from
      conferences. Nearly all had links with an academic institution. NDUs that had the
      support of their Trust's management were able to market their services
      successfully. Our findings indicate that many NDUs have made good progress but
      their clinical leaders are the first to admit that there is much more to be done.

PMID- 9661384
TI  - Increasing collaboration within a multidisciplinary neurorehabilitation team: the
      early stages of a small action research project.
AB  - This paper describes how the process of action research is being used in
      undertaking a team-focused, practice-based project. The problems that the team
      has previously experienced in initiating change are outlined. An explanation is
      advanced as to why action research is an appropriate strategy for the team to
      adopt, and the early stages of the action research project are described. This is
      followed by a discussion of how the outcome of such research can be generalizable
      from one clinical setting to another.

PMID- 9661385
TI  - The health promoting nurse.
AB  - This paper suggests that (i) the dominance of an individualistic philosophy of
      nursing, (ii) nurses' own perceptions of their role and (iii) the
      hospital:community divide are all obstacles to health promotion being well
      integrated into nursing practice. It explores how these obstacles need to be
      overcome in order for the new health promoting nurse to emerge in practice. This
      is an attempt to clearly demonstrate 'who' the health promoting nurse is, 'what'
      she/he does, 'how' she/he works and 'where' she/he works.

PMID- 9661386
TI  - Creating a framework for clinical nursing practice to advance in the West
      Midlands region.
AB  - The West Midlands Regional Health Authority identified a lack of opportunities
      for nurses to develop advanced clinical practice through a recognized programme
      at Postgraduate diploma/Masters degree level. Education for clinical practice
      must be equally grounded in theory and practice. Advanced clinical practice
      requires more than just skills acquisition, it has a much wider remit
      incorporating elements of clinical expertise and higher level decision making,
      research awareness, teaching and role modelling, informing policy making and
      leading in the provision of patient care within individual Trusts. This
      initiative has encouraged universities, trusts and provider units to work
      together to identify and prepare students and staff for their changes in role,
      and to review existing boundaries for practice which will enable new approaches
      to team work and the provision of holistic patient care.

PMID- 9661387
TI  - Will current clinical effectiveness initiatives encourage and facilitate
      practitioners to use evidence-based practice for the benefit of their clients?
AB  - 1996 saw the implementation of Clinical Effectiveness Initiatives by the NHS
      Executive and the Royal College of Nursing to promote the use of evidence-based
      care. This paper examines whether or not nurses will be encouraged and
      facilitated by these initiatives to provide evidence-based care for their
      clients. Both initiatives appear to assume that the use of evidence-based care
      leads to improved client care, but several issues are raised which still need to
      be resolved before this assumption can be made. The NHS Executive advocates the
      use of randomized controlled trials as the method of choice for providing
      evidence of clinical effectiveness. However, this may not necessarily be the best
      methodology for some areas of nursing practice. The paper concludes that the
      Royal College of Nursing's Clinical Effectiveness Initiative has great potential
      to provide the necessary motivation and facilitation, providing other
      professional issues are resolved.

PMID- 9661388
TI  - An evaluation of the lecturer-practitioner role in the independent health care
      sector.
AB  - This study examined the impact of the introduction of lecturer-practitioner (LP)
      roles in four Nuffield Hospitals over a period of two years. A series of
      interviews was conducted with the practitioners themselves, the staff and the
      managers. LPs also maintained structured diaries. Nursing practice in the
      independent sector is influenced by a number of factors, including caring for
      patients in individual rooms and working directly with consultants because there
      are no junior medical staff. Nurses encountered patients with very diverse
      problems, and accordingly needed help to maintain a wide professional knowledge
      base. Nursing staff benefited from the presence of an LP in terms of linking
      theory to practice, role modelling, obtaining career advice and introducing
      change. Non-nursing staff also benefited from the LPs' adoption of an
      interdisciplinary approach to certain care situations. LPs were valued as a
      resource for staff and seen as important in enabling the company to maintain its
      image as a provider of high-quality care. The LP was also well placed to raise
      the profile of nursing in the independent sector through research activities. LPs
      themselves benefited from their experiences and were able to develop their own
      skills.

PMID- 9661389
TI  - Advanced practice nursing in the Nordic countries.
AB  - Changes in the delivery of health care and changes in population characteristics
      and health care requirements mandate changing requirements in nursing education.
      This is necessary to meet patient and family needs and to deliver quality health
      care. This paper describes the background to nursing education in the Nordic
      countries and gives an account of an initiative in Norway to prepare advanced
      practice nurses for clinical practice in this dynamic environment.

PMID- 9661390
TI  - Implementing advanced practice: identifying the factors that facilitate and
      inhibit the process.
AB  - This paper reports the preliminary results of research investigating the factors
      that help or hinder advanced nurse practitioners as they attempt to implement new
      roles in clinical practice. Multiple facilitating and inhibiting factors are
      identified, the majority of which are shared across various clinical settings.
      Factors fall into three categories: re-negotiating relationships; becoming an
      advanced practitioner; and the clinical context and deployment. Whilst the
      results of this case study research are not necessarily generalizable, they
      provide evidence of the lived experience of advanced nurse practitioners
      attempting to implement new roles in a variety of clinical settings following
      their graduation from a Master's degree programme.

PMID- 9661391
TI  - The primary/secondary interface. Cross-boundary teamwork--missing link for
      seamless care?
AB  - Factors for providing a seamless service are given and it is suggested that more
      collaborative interactions between organizational groups are needed to achieve
      this. It is argued that competitive philosophy within the NHS has been
      prohibitive to seamless care. Elements of the White Paper (DoH, 1997) are
      discussed in relation to this. Features of a collaborative organization are
      briefly discussed. Three current 'models' of cross-boundary interaction at the
      point of patient transfer are discussed. A fourth model involving enhanced inter
      sector teamwork with multidisciplinary membership and shared professional,
      management and patient/carer responsibility is proposed.

PMID- 9661392
TI  - Role transition from staff nurse to clinical nurse specialist: a case study.
AB  - Over the last decade, nursing in the United Kingdom has witnessed a major
      development and expansion in the number of Clinical Nurse Specialists. These
      nurses are considered to be experts in their own specialities, have in-depth
      knowledge and provide a service for patients, relatives and staff. There is,
      however, a paucity of literature relating to role transition from experienced
      Staff Nurse to Clinical Nurse Specialist. Using Nicholson's (1984) model of work
      role transition and Wanous' (1992) four-stage model of organizational
      socialization, this study explores the transition of two nurses from experienced
      Staff Nurses to novice Clinical Nurse Specialists.

PMID- 9661393
TI  - Case management in Hong Kong: evaluation of a pilot project in community nursing.

PMID- 9661394
TI  - Advancing nursing practice: the impact for managers.

PMID- 9661395
TI  - Achieving partnership: the contribution of nursing education to the production of
      a flexible workforce.
AB  - AIM: This paper examines education's contribution to labour force reform in the
      nursing profession within the United Kingdom. BACKGROUND: In a globalized society
      there is increasing demand for more flexible forms of working. Nursing faces
      radical change in its employment characteristics if it is to continue to meet the
      health care needs of the population in the new century. ORIGINS OF INFORMATION
      AND DATA ANALYSIS: Key sociological texts and contemporary analysis of nursing
      skill have been analysed and synthesized to identify the dynamic of change in
      nursing and nursing education's contribution to these changes. KEY ISSUES:
      Patterns of upskilling and multiskilling are leading to the breakdown of
      professional role boundaries in the broader workforce. These patterns can also be
      seen in nursing. Upskilling is associated with increased stress and 'risk' for
      the individual, therefore achievement of flexibility is not without cost. Changes
      in the skill level in nursing lead many to conclude that the profession will
      become divided into a core and periphery distinction. This simplistic analysis
      does not account for the complexities of nursing and nursing skill although there
      is clearly a growing need for a 'knowledge and technical elite'. CONCLUSIONS: The
      core-periphery distinction is too simplistic to analyse nursing skills and the
      dynamic of change in the workforce. A radical perspective of nursing
      characterized by workers with a range of skills and competencies is less likely
      to lead to rigid professional boundaries. There is a clear need for multiskilled
      and knowledgeable workers; the 'technical and knowledge elite'. These nurses may
      be recognized as advanced practice nurses. High quality education is required to
      prepare these practitioners. Adaptation of nursing to the postmodern world needs
      to be facilitated by changes in current educational policy and practice.

PMID- 9661396
TI  - Getting started: choice and constraint in obtaining a post after qualifying as a
      registered mental nurse.
AB  - AIMS: To explore the extent to which obtaining a post after qualifying as a
      registered mental nurse (RMN) is a matter of exercising choice or experiencing
      constraints. BACKGROUND: The paper is drawn from the first phase of a
      longitudinal study of the careers of RMNs, commissioned in response to concerns
      about attrition from the mental health nursing workforce. METHODS: Questionnaires
      were sent to all RMNs (n = 550) qualifying from 3-year and post-registration
      courses in four regional health authorities; 80% (447) responded. FINDINGS: Some
      73% had obtained a National Health Service (NHS) psychiatric nursing post shortly
      after qualifying; 95% had hoped to do so. Of those with a post, 71% had obtained
      their first choice of client group. A wide range of professional and personal
      constraints emerged as affecting job choice; lack of NHS posts in preferred
      location and/or speciality was cited most often. CONCLUSIONS: Support and
      guidance may be helpful for nurses experiencing delays in obtaining a post, or
      who are starting careers in a post which is not their first choice.

PMID- 9661397
TI  - Can services marketing concepts be applied to health care?
AB  - AIM: To generate thought and discussion regarding the application of key features
      of generic services which may influence management and marketing decisions in
      health care. BACKGROUND: Health care, as many other services provides benefits to
      the consumer, the quality of which is largely dependent on the interpersonal
      element of the service delivery. Services now dominate the UK economy, and
      consumer participation in service delivery is as important in health care as in
      services in the private sector. ORIGINS OF INFORMATION: There is now an
      established body of research on the nature of services and the particular
      management and marketing challenges posed by service provision. The application
      of general management concepts and tools to the public services is an area of
      current debate. KEY ISSUES: The paper firstly discusses key features of services
      and their application to health care contexts. Secondly, a discussion of
      strategic classifications of services seeks to identify common themes which exist
      across the diverse service sector. CONCLUSIONS: Nursing and midwifery managers
      have much to gain from understanding the use of services management frameworks,
      and have scope for much creativity in adapting generic frameworks for their own
      areas of practice.

PMID- 9661398
TI  - Nursing activities following the introduction of health care assistants.
AB  - AIM: The purpose of this study was to determine changes in the work nature of
      nurses after the introduction of Health Care Assistants (HCAs). BACKGROUND: HCAs
      with a role similar to those adopted in the UK of assisting the nurse were
      piloted in a teaching hospital in Hong Kong. METHOD: A quasi-experimental design
      was used to compare the observed activities of HCAs and nurses in four wards of a
      teaching hospital, before and after the introduction of HCAs. As the amount of
      staff activity is influenced by the amount of work, patient dependency data were
      gained from record reviews and nurse interviews. FINDINGS: HCAs in orthopaedic
      and medical wards provided more basic care than those in surgical and
      gynaecological wards. Nurses in wards with HCAs performed significantly fewer
      activities than nurses in control wards. CONCLUSIONS: HCAs presence accounted for
      a reduction in both direct and indirect care provided by nurses. Overall, HCAs
      provided more basic than technical and indirect care.

PMID- 9661399
TI  - Measuring the unmeasurable: a caring science perspective on patient
      classification.
AB  - AIMS: To give a short historical survey of patient classification and its
      motives, to analyse patient classification and especially the instrument, The
      Oulu Patient Classification more closely from a caring science perspective.
      BACKGROUND: A survey of topical literature and research on patient classification
      show that economic and administrative justifications predominate and the caring
      science connection is weak, almost non-existent. ORIGINS OF INFORMATION: Topical
      literature and research on patient classification and the instrument, The Oulu
      Patient Classification. DATA ANALYSIS: Topical literature and research were
      evaluated from a caring science perspective in accordance with Eriksson's theory
      of caring and the basic concept of man as an entity of body, soul and spirit. KEY
      ISSUES: Patient classification is used in staff planning and is also justified
      from the viewpoint of content, that is, as a method of guaranteeing good quality
      in the care of patients and as an expression of the prevalent caring ideology.
      The concept of man is reduced in current literature and research on patient
      classification. The Oulu Patient Classification is based on a humanistic view of
      man, but man's spiritual and existential needs do not emerge clearly from the
      manual of the instrument. CONCLUSIONS: It is essential for patient classification
      to start from a caring perspective. Correctly dimensioned staffing based on
      patient classification is a prerequisite for good care. This should be combined
      with a caring culture that considers the whole complexity of man in order to make
      good care possible.

PMID- 9661400
TI  - An enrolled nurse conversion course: does it make a difference?
AB  - AIM: This study set out to investigate the effect of a conversion course on the
      careers of enrolled nurses. BACKGROUND: Funding has been made available for
      nurses to convert from second level to first level registration. Managers need to
      know the value of this initiative. METHOD: Questionnaires sent to a sample of 130
      enrolled nurses and semi-structured interviews with eight nurses and one manager.
      Descriptive statistics were used to analyse the questionnaires and themes
      identified from the transcripts of the interviews. FINDINGS: One year after
      completion, participants identified changes in grade, job and further study.
      Interviews revealed a developmental change in their personal and professional
      life. The depth of perceived prejudice towards them remains very powerful.
      CONCLUSION: Converting to first level registration appears to have positive
      outcomes for most nurses in the study and has resulted in wider opportunities for
      their careers and professional development.

PMID- 9661401
TI  - Workload/outcome measurement for hospital educators. Confirming the value of
      education.
AB  - At Vancouver Hospital and Health Sciences Centre, the education department has
      implemented a workload/outcome measurement system to analyze the elements
      necessary to deliver educational services and to identify the outcomes of that
      service at the application and impact levels. The system is unique in that it
      considers the "costs" in terms of the time and money necessary to produce an
      educational product in relationship to the "benefits" of that product to the
      organization. Monitoring workloads can help set work priorities and adjust work
      activities. Measuring outcomes can provide justification for workload by
      determining whether the activity made a difference and can draw attention to the
      importance of removing system barriers and of providing ongoing support in the
      workplace to achieve higher outcomes. This system can be adapted successfully to
      any healthcare facility to make decisions about educational priorities and
      resource allocation.

PMID- 9661402
TI  - Developing self-directed learning modules.
AB  - The authors present a practical, step-by-step process for developing,
      implementing, and evaluating self-directed learning modules for staff development
      and continuing education. The process is described in detail and includes
      specific examples for those who want to develop self-directed learning modules
      that are unique to a particular target population.

PMID- 9661403
TI  - New-building occupancy. The role of nursing staff development.
AB  - Orienting hospital staff to a new patient care facility presents many unique
      challenges for the Nursing Staff Development Department. Today's healthcare
      climate demands that staff orientation to a new facility be done quickly and with
      few disruptions to patient care. Nursing staff development specialists are well
      positioned to lead this process. Their expertise in program design,
      implementation and evaluation, problem solving and communication skills, and
      ability to view the learning needs of hospital staff holistically are vital to a
      successful facility move. This article will describe the opening of a new 150-bed
      inpatient facility in a large acute rehabilitation center. The principles used by
      the Nursing Staff Development Department in this new facility orientation process
      can be applied in multiple health care settings.

PMID- 9661404
TI  - A research-based model of nursing orientation.
AB  - The authors present an orientation model derived from a naturalistic study of a
      nursing orientation program. This model includes the organizational aspects of
      orientation, as well as characteristics related to the person being oriented.
      Included in the model is an affective element of welcoming newcomers to a
      facility and an assessment of clinical competency. In addition, the model
      includes the educational and managerial requirements of the process and
      emphasizes the importance of the preceptor.

PMID- 9661405
TI  - Understanding learning styles. Implications for staff development educators.
AB  - The authors present information for understanding diverse learning styles among
      RNs. Various learning-style assessment tools are presented. Emphasis is placed on
      the use of a learning-style instrument that addresses multiple learning-style
      constructs. Implications for staff development educators are discussed.

PMID- 9661406
TI  - Discharge planning. Implications for staff development educators.
AB  - Discharge planning is a patient right and is mandated by legislation,
      institutions that provide credentials, and professional organizations. This study
      was conducted to assess nurses' knowledge and perceptions of the roles and
      responsibilities in the discharge planning process. Findings of this study
      indicated a difference in knowledge of discharge planning between nurses who have
      earned an associate degree and nurses who have earned a bachelor's degree. Staff
      development educators may use this information to justify and develop educational
      programs concerning discharge planning.

PMID- 9661407
TI  - Preoperative teaching in the preadmission clinic.
AB  - In this article, the author proposes that instructional design be used as a
      foundation for a teaching model in the preadmission clinic and that the
      educational process be based on theories developed within the fields of health
      care and adult education. Furthermore, the author suggests that the process of
      patient education, as conducted within the preadmission setting, should
      necessitate an assessment of the general characteristics of the adult as a
      learner, of the specific characteristics of the adult as a presurgical patient,
      and of the unique individual cognitive processes distinctive to each patient.
      This information should be integrated in a new framework to create a
      comprehensive and personalized patient teaching model.

PMID- 9661408
TI  - Developing a career in the mental health services: guidance for student nurses.
AB  - Current concern about a shortage of nurses has led to attention focusing on the
      provision of career guidance as a strategy to facilitate retention in the
      workforce. This paper presents findings on career guidance provided for
      psychiatric nursing students, and thus adds to the very small volume of research
      that exists on guidance in nursing generally. Questionnaires were sent to 556
      Registered Mental Nurses shortly after qualification; 80% responded. This
      represented the first phase of a longitudinal study of these nurses' careers.
      Participants were asked whether they had received information about career
      pathways that might be pursued, educational opportunities available and work
      experience outside the NHS. If not they were asked whether they had wanted such
      information. They were also asked whether they had been given advice about
      planning their own career. Only a minority of respondents had received
      information or advice, but the majority would have liked to have done so. The
      findings are discussed in the context of whether there is a need for career
      guidance and, if so, by whom it should be provided.

PMID- 9661409
TI  - Teaching of communication skills in Spanish nursing schools: an overview.
AB  - The main objective of this study is to review the teaching of communication
      skills in Spain as part of the nursing curriculum. A survey was carried out to
      identify the practical and theoretical issues pertinent to this question. Forty
      Spanish Nursing Schools took part. Our survey discovered that communication
      skills are not generally considered in the selection process of the students
      because personal interviews are rarely used. Communication skills are taught in
      the first and second years, mainly in Fundamentals of Nursing and subjects
      related to Psychology and Mental Health. Nursing and psychology were the
      predominant professional background of the teachers. Lectures, discussion groups
      and workshops were the main teaching methods. The assessment, when it existed,
      was often theoretical and, occasionally, using a real patient or a written case
      report. The authors propose that the knowledge of the teaching situation in Spain
      is the starting point for any future projects on communication.

PMID- 9661410
TI  - Prevalence of auditory hallucinations in nurses in mental health.
AB  - Seventy-nine nurses and student nurses working in the mental health field were
      asked to complete a questionnaire that asked about the prevalence of their
      experience of events that might be considered as examples of auditory
      hallucinations. Eighty-four per cent of the 55 nurses who returned the
      questionnaire described having experiences that might be described as auditory
      hallucinations. This level of prevalence is broadly consistent with other
      studies, and the difference between voices considered to indicate 'schizophrenia'
      and voices perceived as normal or unimportant is discussed. The relevance of
      these findings for the process of diagnosis and for the attitudes of nurses
      working in the mental health field towards voices reported by clients is
      highlighted.

PMID- 9661411
TI  - Subtle coercion in psychiatric practice.
AB  - Making nursing decision for patients who cannot communicate their own wishes and
      needs is a common problem in psychiatric and mental health nursing. The aim of
      this article is to present the findings of a qualitative study focused on
      situations in which patients do not cooperate with a nursing decision about what
      should be done for them. The design of the study utilized some steps associated
      with the grounded theory method. Data were collected from unstructured interviews
      with 10 British nurses with long experience in psychiatric nursing. By
      implementing the strategy of constant comparative analysis of the transcribed
      interviews, it was found that nurses use different types of subtle coercion in
      order to achieve their own goals for the patient. These goals were justified as
      being in the best interest of the patient. The main components of subtle coercion
      are part of a process consisting of: assessing a patient's competency for self
      choice; acting strategically; modifying the principle af autonomy; justifying
      strategies; and reflecting ethically on the action taken. The study indicates
      that further empirical investigation of clinical situations involving subtle
      coercion is required. Particular attention should be paid to organizational
      factors and how these contribute to the use of subtle coercion. A specific
      question that needs to be theoretically and empirically explored is, can coercion
      be justified as 'ethically right' in some situations but not in others?

PMID- 9661412
TI  - Creativity and psychic distress in artists, writers and scientists: implications
      for emergent models of psychiatric nursing practice.
AB  - Many of the great discoveries and developments in the sciences and the arts were
      made by people who were 'mentally different'. Some such pioneers or innovators
      had experiences that were indistinguishable from the phenomena defined as mental
      illness (or madness). It has been argued that such experiences are a necessary
      constituent of the creative process, and that this may apply to the sciences as
      much as to the arts. Increasingly, scientists propose a means by which it may be
      possible to identify (and eliminate) the factors that influence the altered
      states associated with mental illness. This may be an appropriate time to review
      the cultural and social significance of all forms of 'madness', especially in the
      light of emerging models of psychiatric nursing practice.

PMID- 9661413
TI  - Influencing mental health nursing practice through the teaching of research and
      theory: a personal critical review.
AB  - This paper will critically review the factors that influence the teaching of
      theory and research to mental health nurses. Following a brief historical review
      it is asserted that current educational approaches fail to address the complexity
      and context-dependent nature of mental health nursing practice. The author then
      argues for a radical approach to education which will enable students and
      practitioners to engage critically in deconstructing and developing theories that
      illuminate and help us understand the multiple realities of our post-modern
      professional world. In conclusion, the author provides an example of a casework
      based curriculum that emphasizes the ways in which clinical experience with
      clients in a range of contexts should be the main focus of knowledge and skill
      development for the emerging profession of mental health nursing.

PMID- 9661414
TI  - The role of mental health nursing in the prevention of child sexual abuse and the
      therapeutic care of survivors.
AB  - This paper is primarily designed to stimulate discussion and debate on the role
      of the mental health nurse dealing with survivors of sexual abuse. The authors
      contend that, in reality, all nurses should be prepared through education and
      training to treat the sufferers of emotional and spiritual pain, regardless of
      from where the hurting stems. The need for nurses to open their eyes and
      acknowledge the agony and distress caused to children as a result of abuse by
      adults is highlighted. So too is the necessity for nurses to enhance their own
      unique and specific practice. Nurses (and particularly mental health nurses) have
      a role in promoting a healthy generation of children--children who are looked
      after and protected by caregivers and not by caretakers. As the result of nurses
      advocating healthy caregiving and healthy relationships children may never need
      to suffer from inhumane and denigrating acts against their very beings. Nurses
      have no excuse for being unable to imagine child sexual abuse. Therefore they
      have no excuse for not being prepared to deal with the resulting, excruciating
      pain. It is both uncaring and inhumane for nurses not to be prepared to accept
      the sharing of such emotionally painful and disturbing experiences. Mental health
      nurses have a genuine role in offering therapeutic care to victims and survivors.
      This paper concludes by exploring and examining the nurse's role in counselling
      survivors of child sexual abuse.

PMID- 9661415
TI  - Staff perceptions of substance use among acute psychiatry inpatients.
AB  - This paper reports on a small-scale study undertaken in two inner city acute
      psychiatric wards to identify the proportion of patients known to use drugs or
      alcohol and the perceptions of staff regarding these patients. Data collection
      involved a retrospective audit of patient notes and the administration of a
      questionnaire to nursing staff. The findings were broadly consistent with other
      research studies. Over half of the patient sample was reported to use illicit
      drugs or alcohol and in one third of cases this use was thought to have
      contributed to their current admission. Questionnaire results indicated that
      staff felt ill-equipped to offer an adequate response although all respondents
      welcomed opportunities to develop their knowledge and skills. The findings are
      discussed in light of the existing literature, and some tentative conclusions are
      drawn concerning the development and provision of effective integrated services
      for individuals with psychiatric and psychoactive substance use disorders.

PMID- 9661416
TI  - Paradigms for mental health nursing: fragmentation or integration?
AB  - Debate about the best paradigm for mental health nursing is compounded by threats
      from mainstreaming and genericism. In nursing education, integrated practice may
      have been devalued in a matrix of reductionist disciplines. The 'gendered' nature
      of professional knowledge may create a schismatic and self-defeating attitude in
      nurses. Conversely, nurses may be exhorted to adopt a 'male' paradigm in order to
      gain academic credibility, in which the caring dimension may be lost. Other
      polarities such as ideological distinctions between treatment in hospital and
      care in the community lead to conceptual confusion. These schisms in care are
      detrimental to both professionals and users. The writers argue that these
      tensions may be addressed in an 'androgenous' model which presents a challenge to
      both value systems, rejects the dominance of schismatic models, and offers the
      potential for a new professional integrity.

PMID- 9661417
TI  - Mental health nursing students and their knowledge of the nurses' holding power
      (section 5/4).

PMID- 9661418
TI  - The utilization of Peplau's theory of nursing in working with a male survivor of
      sexual abuse.

PMID- 9661419
TI  - [Holding hands is no thumb twiddling].

PMID- 9661420
TI  - [The need for care is rising. Social consequences of demographic developments in
      Germany].

PMID- 9661421
TI  - [Chemotherapy and pain therapy at home. Home infusion therapy].

PMID- 9661422
TI  - [Ambulatory artificial nutrition in chronic diseases].

PMID- 9661424
TI  - [Quality assurance in diabetes therapy].

PMID- 9661423
TI  - [New methods are oriented towards the quality of life. The scope of treatment for
      prostatic neoplasms has widened].

PMID- 9661425
TI  - [Exact blood sugar measurements in premature and newborn infants].

PMID- 9661426
TI  - [Eye complications in diabetes mellitus].

PMID- 9661427
TI  - [Anorectal and perianal complications in Crohn disease].

PMID- 9661428
TI  - [Psychologists who created a school (III). Alfred Adler (1870-1937)].

PMID- 9661429
TI  - [On helping. 2. The fatal compulsion to help].

PMID- 9661430
TI  - [Drug-dependent nurses. From helping syndrome to addiction].

PMID- 9661431
TI  - [Longing for the full life].

PMID- 9661432
TI  - [Counseling for mothers and fathers. They who know themselves are better prepared
      to help others].

PMID- 9661433
TI  - [Citizens' initiative on "Protection of life and environment from gene
      manipulation". Position of the Central Board and the Ethics Commission of the
      Swiss Nursing Society].

PMID- 9661435
TI  - [The burnout syndrome: from idealism to exhaustion].

PMID- 9661434
TI  - [A woman in her best years].

PMID- 9661436
TI  - [Without a contract but not without rights].

PMID- 9661437
TI  - [A very sick patient: work].

PMID- 9661438
TI  - [Elaboration of quality standards. How to fight effectively against infections].

PMID- 9661439
TI  - [A place of respite for the destitute].

PMID- 9661440
TI  - [Nursing care in neuro-rehabilitation: a therapeutic stronghold].

PMID- 9661441
TI  - [Geneva: discrimination in nursing. Towards equality, with full sail ahead].

PMID- 9661442
TI  - Professional ethnocentrism and shared learning.

PMID- 9661443
TI  - The preparation of teachers for shared learning environments.
AB  - This paper outlines a project designed to evaluate shared learning in educational
      programmes of preparation for nursing, midwifery and health visiting teachers in
      England, building upon the literature review described in part 1 of this report
      and a more detailed account available elsewhere. A dearth of research into shared
      learning and teachers' roles was noted. To address this, an illuminative
      evaluation approach was taken to elicit quantitative and qualitative data from
      lecturers on teacher preparation programmes, new teachers who had recently
      completed these programmes, and more experienced teachers working in colleges of
      nursing and midwifery. This study that a number of shared learning initiatives
      exist in teacher preparation centres and colleges of nursing and midwifery. There
      was general agreement between the participants that it was necessary to prepare
      teachers to be facilitators in shared learning environments; however, no
      particular type of preparation was considered essential. The implications for
      future work are considered.

PMID- 9661444
TI  - Viewing an old issue through a new lens: a critical theory insight into the
      education--practice gap.
AB  - The education-practice gap is not new to lecturers or practitioners and has been
      widely discussed in previous literature. This paper explores issues relating to
      this concept from Habermas' critical theory viewpoint. The historical and
      philosophical underpinnings of critical theory, as well as its central elements,
      are described. A recent incident involving one of the authors stimulated
      reflection on the issue of clinical assessment and the communication gap between
      teachers and practitioners. Viewing the incident through a critical theory lens
      allowed two main themes to be explored: the balance of knowledge and power in the
      education-practice arena and the personal issues involved in failing a student.
      Several questions emerged during this reflective period. Are nurses prepared to
      search for answers to these questions?

PMID- 9661445
TI  - An exploratory study of similarities and differences between senior students from
      different pre-registration nurse education courses.
AB  - A triangulation design using two simulations, non-participant observation and a
      semi-structured interview to explore senior student nurse performance in South
      East England is described. A comparison of student nurse performance (registered
      general nurse [RGN] programme n = 34; registered nurse Project 2000 diploma
      programme n = 34; integrated degree programme n = 31) indicated many similarities
      but also some important differences in outcomes which included: a more systematic
      approach to information-seeking, better care-planning skills and higher quality
      nurse performance among integrated degree programme participants; use of a model
      and the immediate role of the nurse to guide information-seeking and better care
      planning skills and weaknesses in clinical nurse performance among RGN programme
      participants; and weaknesses in the information-seeking, care-planning and
      clinical nurse performance among Project 2000 diploma participants. There were no
      significant differences between the clinical performance scores of the RGN and
      diploma programme participants. The interview data suggested that the integrated
      degree programme participants had a client focus in contrast to the professional
      focus of RGN and Project 2000 diploma participants. The findings, however, must
      be viewed within the context of an exploratory study of limited sample size. The
      research was funded by the English National Board for Nursing, Midwifery and
      Health Visiting.

PMID- 9661446
TI  - Assessment of practice in pre-registration nurse education and the development of
      a skills acquisition manual.
AB  - It has been suggested that Project 2000 training has not taken account of the
      need to assess the development of specific nursing skills. This could result in
      nurses who may be in a vulnerable position upon qualification regarding the
      expectations of their skills performance. A new initiative has been developed at
      the University of Luton, which enables specific skills to be assessed for pre
      registration students during the Common Foundation Programme. This document is
      discussed here and is the precursor to a wider research study proposed to be
      undertaken upon completion of the evaluation.

PMID- 9661447
TI  - The sense of coherence among nurse educators in Finland.
AB  - In his salutogenic model, Antonovsky defines the sense of coherence (SOC) as a
      personality dimension which is hypothesized to facilitate stress management and
      to contribute to overall well-being. The SOC scores of Finnish nurse educators
      were determined using the 13-item version of the SOC questionnaire.
      Questionnaires were sent to 706 Finnish nurse educators, and data from 477 (68%)
      educators were analysed. The mean score of respondents' SOC was 66.9 (SD 0.47,
      range 34-88). Cronbach's alpha was 0.81. The SOC was lower among older
      respondents. The more freedom individuals had to choose their teaching field, the
      higher the SOC. Thus, although age explained a significant proportion of
      variance, its contribution to the total proportion of variance explained was
      quantitatively less important than that of freedom to choose duties. Other
      background data were not related to SOC. There was a significant positive
      relationship between the SOC score and the opinions of nurse educators about
      interaction in the working community, joy of work, workload, negative stress,
      symptoms of diseases, atmosphere in the college, evaluation of own competence,
      balance between work and leisure time, own health, and use of drugs.

PMID- 9661448
TI  - The role of Project 2000 educated nurses in health promotion within the hospital
      setting.
AB  - This study is concerned with the role of Project 2000-educated nurses in health
      promotion within the hospital setting. Historically nurses have been viewed as
      having a role to play in promoting the health of the people for whom they care.
      More recently, with the advent of the Health For All Movement initiated by the
      World Health Organization in 1978, the attention has again been focused on what
      nurses can do towards attainment of this goal, although most of the research has
      been carried out in relation to community nurses and primary care. Changes in
      nurse education, specifically that of Project 2000 nurse education, have been
      hailed as the opportunity to equip nurses with knowledge and skills appropriate
      to the task, which have been seen as lacking from many nurse educational
      programmes. Early work on this issue has produced conflicting findings as to the
      success of these educational changes. This study used an exploratory, qualitative
      approach to investigate what aspects of health promotion in the hospital setting
      are being carried out by nurses who have undergone Project 2000 nurse education
      within a college of nursing and midwifery in Scotland, and whether these nurses
      feel that they have been adequately prepared for this role during their
      educational programme. Findings suggest that the nurses interviewed were working
      with very wide perceptions of health promotion which included the more radical
      aspects of health promotion such as negotiation, collaboration and empowerment.
      Health promotion was also seen to include psychosocial factors that influence the
      health of individuals. The nurses interviewed in general felt that their
      education had prepared them for a role in health promotion. The value of clinical
      placements in facilitating the developing the skills for health promotion was
      established.

PMID- 9661449
TI  - An examination of the role of learning environments in the construction of
      nursing identity.
AB  - The interplay between the development of a nurse's identity within the world of
      nursing, and the construction of relevant nursing concepts is by necessity a
      difficult and complex one. It is in part grounded in the theories of social
      interaction, concept formation, and relevant peripheral participation in the
      workplace, all of which can be related to the nursing role. These issues are
      considered here primarily from the sociocultural viewpoint of Vygotsky, bringing
      together the important role of significant participants in the nurse's learning
      experiences, predominantly peers, and examining briefly the effects of such a
      viewpoint in relation to nursing education. How best nursing knowledge may be
      structured to optimize the learner's educational experiences, and how best the
      learning environment of the student may be utilized to maximum educational
      benefit still remain complex questions. With moves towards more competence-based
      learning such interactions may be crucial to our understanding of the
      complexities of learning in what are essentially very practical-based
      environments, and at the same time allow us to acknowledge the important
      mechanisms involved in concept acquisition and transferability, a notion central
      to lifelong learning.

PMID- 9661450
TI  - 'Being there': learning through active participation.
AB  - Students engagement in learning is predicated not only on interest but on the
      perception of relevance to their needs. A hermeneutic interpretation of narrative
      student evaluation data from an introduction to nursing lecture course that was
      taught by means of a practice-based phenomenological approach revealed a pattern
      of student learning in which students moved from detachment to active
      participation in their learning. The stories shared by nurses in the practice
      setting were instrumental in introducing students to the world of nursing and
      facilitating a sense of belonging. Once engaged in the experience, students
      looked for opportunities to become active participants in their learning. A
      practice-based phenomenological approach to a theory course maximizes
      opportunities for student participation. Active reflection and integration allow
      students to make their own connections between theory and practice.

PMID- 9661451
TI  - An evaluative study of pre-registration nursing students' skills in basic life
      support.
AB  - Basic life support is identified as a skill in which the public expects nurses to
      be competent. However, a review of the literature suggests that many nurses are
      not competent in this skill. This study describes the performance of nursing
      students from three branches of nursing in basic life support skills. Individual
      performances were generally unsatisfactory, and significant differences between
      students from the different branches were noted. The implications of the study
      are of concern for all involved in nurse education.

PMID- 9661452
TI  - The poster presentation: what value to the teaching and assessment of research in
      pre- and post-registration nursing courses?
AB  - Poster presentations have proved to be a popular method of displaying information
      at conferences, and are being used increasingly as a teaching method. Innovative
      strategies for teaching and assessing research need to facilitate students'
      achievement of research skills required for practice. These are outlined by the
      Department of Health, and emphasize the development of research literacy. Using
      the poster presentation as a teaching and assessing strategy on diploma level
      courses (Project 2000 and ENB 870 introduction to the Understanding and
      Application of Research) has proved to be valuable in developing vital research
      awareness skills and in harnessing enthusiasm for research. Students imply a
      sense of achievement gained through the process of developing the poster and the
      production of the poster itself. Herein lies the value of the poster
      presentation, for it allows the development of crucial research literacy skills
      which can be widely used in professional practice and future professional
      education.

PMID- 9661453
TI  - Information literacy: a resource for nurses as lifelong learners.
AB  - The use of information technologies throughout the world continues to increase
      rapidly and inexorably. Information exchange is rapidly becoming a major economic
      commodity. The short half-life of professional and technical knowledge
      necessitates nursing graduates having generic qualities that will enable them to
      adapt to technical change and cope with an 'information overabundant
      environment'. Today's nurses must have the capacity to access information, both
      physically and intellectually; that is, they must be information-literate. Nurses
      need to be discerning information consumers in order to acquire knowledge and
      skills in relation to their jobs and social roles and as participants of a
      democratic society. This paper examines information literacy as a critical
      resource for nurses as lifelong learners, and explores how information literacy
      is situated in the nursing literature. The authors pose two questions. Firstly,
      just how information-literate and aware of information literacy is the nursing
      profession? Secondly, how can the attitudes, skills and knowledge associated with
      information literacy be fostered, cultivated and attained in nursing education?

PMID- 9661454
TI  - Do mention the war.

PMID- 9661455
TI  - The ideal home expedition.

PMID- 9661456
TI  - A date for your diary.

PMID- 9661457
TI  - What happened to the midwife in the case of the woman forced to have a caesarean.

PMID- 9661458
TI  - Life after birth.

PMID- 9661459
TI  - Nurses have been pushed away from the bedside into areas where they are least
      effective.

PMID- 9661461
TI  - Whose baby.

PMID- 9661462
TI  - Beyond miracle babies.

PMID- 9661463
TI  - The pregnancy police?

PMID- 9661464
TI  - Hounded by pain.

PMID- 9661465
TI  - Male catheterisation--2.

PMID- 9661466
TI  - A lesson for life.

PMID- 9661467
TI  - One swallow can make a summer.

PMID- 9661468
TI  - Life-saving is not always dramatic.

PMID- 9661469
TI  - A day to remember.

PMID- 9661470
TI  - An important message.

PMID- 9661472
TI  - Face to face. Interview by Eileen Fursland.

PMID- 9661471
TI  - A nurse, but a person too.

PMID- 9661473
TI  - In our parent's shadow. Sickle cell anaemia.

PMID- 9661474
TI  - The management of bone infection in orthopaedic patients.

PMID- 9661475
TI  - A model of psychosocial care for severe personality disorder.
AB  - This paper describes the development of a preliminary model of psychosocial
      outreach nursing for patients with severe personality disorder. Through a
      grounded theory approach the outreach nurse evaluates their role and spheres of
      psychosocial intervention. Psychodynamic theory enhances an understanding of the
      nurse-patient relationship and the nature of the patient's difficulties,
      facilitating appropriate nursing interventions.

PMID- 9661476
TI  - The unsound barrier.

PMID- 9661477
TI  - A new lease of life.

PMID- 9661478
TI  - Body building.

PMID- 9661479
TI  - Inside stories.

PMID- 9661480
TI  - Nutritionally at-risk groups in the community.
AB  - A balanced and varied diet is the basis of good health. There are some groups of
      people, however, whose circumstances make it difficult for them to achieve this.
      Nurses can play a valuable role in helping these people make healthy dietary
      choices, although in some cases nutritional supplements may be necessary.

PMID- 9661481
TI  - A boost to the system.
AB  - This article discusses nutritional support for patients with HIV. It examines the
      causes and effects of nutritional difficulties, and explores the aims and methods
      of providing nutritional support. A patient's nutritional status depends on
      whether they are symptomatic--as asymptomatic patients do not generally
      experience nutritional problems.

PMID- 9661482
TI  - [Hocus pocus in health insurance?].

PMID- 9661491
TI  - [Care in nursing homes is deteriorating dramatically: "A slap in the face of
      those in need of care"].

PMID- 9661493
TI  - [How dangerous are multiresistant bacteria in the hospital].

PMID- 9661494
TI  - [The Xanthen initiative started programs for the weaning of smokers. It works
      better in a group].

PMID- 9661495
TI  - [An extended report at the time of patient transfer may ease adaptation].

PMID- 9661496
TI  - [Surgical interventions in the aged 2. In emergency surgery the medically
      feasible has to be the guiding principle].

PMID- 9661498
TI  - [Building relationships in nursing: confidence has to be developed].

PMID- 9661497
TI  - [Only equally competent nursing personnel should be in the employment market].

PMID- 9661499
TI  - [Patient-nurse-physician--a relational triangle in the hospital.
      Interprofessional cooperation among equal partners is obligatory].

PMID- 9661501
TI  - [When the operating room patient becomes a customer].

PMID- 9661502
TI  - [Continuing education for managing nursing personnel from the east and west:
      acting ethically or callously?].

PMID- 9661503
TI  - [The helpless helpers are seeking the limelight].

PMID- 9661504
TI  - [The market for continuing education for nurses has started to move].

PMID- 9661505
TI  - [Quality assurance in times of cut-backs. 1. Man has to take the center in the
      hierarchy of value].

PMID- 9661506
TI  - [Continuing education towards the specialty "Rehabilitation". Opinion of students
      from 5 courses].

PMID- 9661508
TI  - [Contamination of clothing while using protective clothing. The spread of germs
      can be reduced].

PMID- 9661509
TI  - [Transplantation legislation: extended consent solution as a Salomonic middle
      course].

PMID- 9661510
TI  - [Traditional Chinese medicine--a path to health: a Chinese pharmacist affords a
      glimpse into far-eastern healing].

PMID- 9661511
TI  - [Work in humanitarian aid: gratitude is a beautiful reward].

PMID- 9661512
TI  - [Nursing and nursing education in Wales: "I was strongly impressed by the team
      oriented way of working"].

PMID- 9661513
TI  - [Hospital hierarchy: for what do we need which elite?].

PMID- 9661514
TI  - [Various ways of measuring body temperature: the individual standard temperature
      has to be known].

PMID- 9661515
TI  - [Deontologic nursing code].

PMID- 9661516
TI  - [The person and nursing care].

PMID- 9661517
TI  - [The psychosocial phenomenon of human aging].

PMID- 9661518
TI  - [Caring for the polytraumatized adolescent].

PMID- 9661519
TI  - [Nursing and the Internet].

PMID- 9661520
TI  - [Pastoral care for AIDS patients].

PMID- 9661523
TI  - [Tracheostomy: nursing care and associated problems].

PMID- 9661521
TI  - [Children and their kidneys. Nursing testimony].

PMID- 9661524
TI  - [Aging].

PMID- 9661525
TI  - [Psychodynamic study of senescence].

PMID- 9661526
TI  - [Interventions in old age homes].

PMID- 9661527
TI  - [Art therapy and aging in an institution].

PMID- 9661528
TI  - [Photolanguage, a group psychotherapy].

PMID- 9661529
TI  - [The positives in old age. How to succeed during this time of life].

PMID- 9661530
TI  - [Psychiatric nursing care in the street].

PMID- 9661531
TI  - [Neurosis cut into four. Experiences of a nurse teaching psychiatry in a
      university nursing school].

PMID- 9661532
TI  - [Caring body communications].

PMID- 9661533
TI  - [The nursing profession is in danger of disappearing].

PMID- 9661534
TI  - [Arches association. Interview by Claude Criel].

PMID- 9661535
TI  - Do we finally have a technique for determining how "blocked" patients are under
      general anesthesia?

PMID- 9661536
TI  - Automated electrocardiograph ST segment trending monitors: accuracy in detecting
      myocardial ischemia.
AB  - Continuous automated ST segment trending devices (ST trending monitors) are
      included in most new operating room electrocardiography (ECG) monitors to
      facilitate ischemia detection, but their efficacy is not well validated.
      Therefore, we compared their accuracy with that of Holter ECG recorders in
      detecting ST segment changes (both analyzed offline) in 94 patients undergoing
      coronary artery bypass graft surgery. Holter ECG tapes were analyzed using
      standard criteria for determining ECG ischemic episodes, which were compared with
      those measured by the ST trending monitors. Overall, 42 ischemic episodes were
      detected by using the Holter monitor in 30 patients. Of the 42 episodes, 38 (90%)
      were also detected by the ST trending monitors. Sixteen episodes of ST segment
      deviation were detected by the ST trending monitors, but not by the Holter. The
      sensitivity of the three ST trending monitors in detecting ischemia was 75%, 78%,
      and 60% for the Marquette (Milwaukee, WI), Hewlett Packard (Andover, MA), and
      Datex (Helsinki, Finland) monitors, respectively, with a specificity of 89%, 71%,
      and 69% relative to the Holter. Compared with the HP and Datex monitors, the
      Marquette monitor has the best agreement with the Holter (K 0.64). Conditions in
      which ST trending monitors may be inaccurate were identified and included the
      appearance of small R-wave amplitude, drifting baseline, and during periods of
      conduction abnormalities and pacing. We conclude that ST trending monitors have
      only moderate sensitivity and specificity (< 75% overall) in accurately detecting
      ECG ST segment changes compared with Holter ECG recordings. Therefore, sole
      reliance on ST trending monitors for the detection of myocardial ischemia may be
      insufficient. IMPLICATIONS: Using Holter recordings as the reference standard for
      detection of intraoperative ischemia, ST trending monitors were found to have
      overall sensitivity and specificity of 74% and 73%, respectively. Several
      conditions contribute to the inaccuracy of ST trend monitoring, and additional
      modification of their performance is necessary to achieve better agreement with
      the Holter analysis.

PMID- 9661537
TI  - Nurse-administered subcutaneous morphine is a satisfactory alternative to
      intravenous patient-controlled analgesia morphine after cardiac surgery.
AB  - There are no comparisons of i.v. patient controlled analgesia (i.v. PCA) versus
      nurse-administered subcutaneous (NA s.c.) morphine for acute postoperative pain.
      We undertook a prospective, randomized, controlled clinical trial of 80 cardiac
      surgical patients to compare i.v. PCA with NA s.c. morphine for postoperative
      pain control. Visual analog scale (VAS) pain scores at rest and with movement,
      daily verbal pain relief scores, and side effect profiles were not significantly
      different. Total morphine requirements in the two groups were not significantly
      different. A physiotherapist's evaluation of the effectiveness of analgesia for
      chest physiotherapy revealed no difference between the two groups. We conclude
      that NA s.c. morphine, administered as required (up to hourly), is a satisfactory
      alternative to i.v. PCA morphine after cardiac surgery. IMPLICATIONS: In a
      prospective, randomized study, we have shown that nurse-administered subcutaneous
      morphine is a satisfactory alternative to i.v. patient-controlled analgesia after
      cardiac surgery.

PMID- 9661538
TI  - Changes in cerebral oxygen uptake and cerebral electrical activity during
      defibrillation threshold testing.
AB  - During cardioverter-defibrillator implantation, repeated episodes of ventricular
      fibrillation (VF) are induced. Insufficient recovery of oxygen metabolism may
      cause neurological sequelae. In this prospective clinical study, we monitored the
      electroencephalogram (EEG), middle cerebral artery blood flow velocity (Vmca),
      and jugular bulb oxygen saturation and estimated cerebral oxygen uptake. Results
      were analyzed for tests requiring a single shock (Group 1) and tests requiring
      multiple shocks for defibrillation (Group 2). Immediately after the induction of
      VF, the mean arterial blood pressure (MAP) decreased to < 30 mm Hg, and the Vmca
      decreased to 0 cm/s. The EEG showed ischemic changes consisting of a decrease of
      fast, and an increase of slow, activity, progressively declining to
      isoelectricity within 11 +/- 2 s. After defibrillation, the MAP recovered rapidly
      regardless of the arrest duration (3 +/- 2 s). The EEG recovered within 17 +/- 9
      and 22 +/- 12 s, respectively, for Groups 1 and 2 (P < 0.05) and did not reveal
      ischemic changes until induction of a subsequent arrest. In Group 1, the cerebral
      oxygen uptake increased to 191% +/- 31% of baseline values and returned to
      baseline in 16 +/- 7 s, whereas in Group 2, it increased to 229% +/- 38% (P <
      0.05), followed by a significant decrease to less than baseline (85% +/- 18%; P <
      0.005), and returned to baseline simultaneously with the Vmca. We conclude that,
      although restoration to normal of the EEG and cerebral oxygen uptake coincide in
      short arrests, EEG recovery underestimates metabolic recovery after tests
      requiring multiple shocks. IMPLICATIONS: Short test intervals have been mentioned
      as a cause of neurological sequelae after cardioverter-defibrillator
      implantation. This study demonstrates that although all systemic hemodynamic
      variables and the electrocardiogram may have returned to normal, cerebral oxygen
      uptake may still be depressed for a considerable time, especially after tests
      requiring two or more shocks.

PMID- 9661539
TI  - The hemodynamic effects of hypoxemia in anesthetized pigs: a comparison between
      right heart catheter and echocardiography.
AB  - During hypoxemia, hypoxic pulmonary vasoconstriction and tachycardia are often
      observed in association with increases in pulmonary artery pressure and cardiac
      output. Nevertheless, the hemodynamic consequences of hypoxemia have never been
      evaluated by echocardiography and simultaneously compared with invasive
      hemodynamic variables. Fourteen open-chest, anesthetized piglets (weight 29-36
      kg) were submitted to progressive hypoxemia and reoxygenation. Usual invasive
      hemodynamic variables were obtained from peripheral and central heart catheters.
      Direct epicardial echocardiography was used to measure right and left ventricular
      areas on a short-axis view at mid-papillary level. The mean pulmonary artery
      pressure (MPAP) increased with pulmonary vascular resistance in a dose-related
      manner as the fraction of inspired oxygen (FIO2) declined from 0.5 to 0.12. The
      MPAP correlated with right ventricular end-diastolic area (RVEDA) only at FIO2
      0.08. There was a 49% reduction in left ventricular end systolic wall stress
      (LVESWS) between FIO2 0.5 and 0.08. Left ventricular ejection fraction area
      (LVEFA) increased by 33% above baseline and correlated with the decrease in
      LVESWS. No correlation was observed between left ventricular end-diastolic area
      and pulmonary artery occlusion pressure or left atrial pressure and between
      cardiac output and LVEFA. Systemic vascular resistance underestimates the
      magnitude of changes in LVESWS but overestimates the afterload compared with
      LVESWS. This study demonstrates that, for the lowest FIO2 (0.08), changes in MPAP
      correlated with changes in RVEDA but not in pulmonary vascular resistance.
      Moreover, LVESWS decreases significantly in a dose-related manner under
      progressive hypoxemia and normalizes immediately after reoxygenation. This study
      also shows that, under hypoxemic conditions, echocardiography enhances
      understanding of hemodynamic changes compared with right heart catheterization
      alone. IMPLICATIONS: Acute hypoxemia in pigs is responsible for pulmonary
      vasoconstriction-induced pulmonary hypertension (which is restricted by the right
      ventricular failure), as well as a PaO2-dependent decrease in left ventricular
      afterload. These changes are better displayed by echocardiography than by right
      heart catheter.

PMID- 9661540
TI  - Pulmonary effects of methylprednisolone in patients undergoing coronary artery
      bypass grafting and early tracheal extubation.
AB  - Numerous clinical studies suggest that methylprednisolone may facilitate early
      tracheal extubation after cardiac surgery, yet no investigation has rigorously
      examined the use of the drug in this setting. In this prospective, randomized,
      double-blind, placebo-controlled study, we examined the pulmonary effects of
      methylprednisolone in patients undergoing coronary artery bypass grafting (CABG)
      and early tracheal extubation. Sixty patients undergoing elective CABG and early
      tracheal extubation were randomized into two groups. Group MP patients received
      i.v. methylprednisolone (30 mg/kg during sternotomy and 30 mg/kg during
      initiation of cardiopulmonary bypass) and Group NS patients received i.v. placebo
      at the same two times. Perioperative management was standardized. Alveolar
      arterial (A-a) oxygen gradient, lung compliance, shunt, and dead space were
      determined four times perioperatively. Postoperative tracheal extubation was
      accomplished at the earliest appropriate time. Both groups exhibited significant
      postoperative increases in A-a oxygen gradient and shunt (P < 0.000001 for each
      group) and significant postoperative decreases in dynamic lung compliance (P <
      0.000001 for each group). Patients in Group MP exhibited significantly larger
      increases in postoperative A-a oxygen gradient (P = 0.001) and shunt (P = 0.001)
      compared with patients in Group NS. Postoperative alterations in dynamic lung
      compliance, static lung compliance, and dead space were not statistically
      significant between the groups. The time to postoperative tracheal extubation was
      prolonged in Group MP patients compared with Group NS patients (769 +/- 294 vs
      604 +/- 315 min, respectively; P = 0.05). Methylprednisolone was associated with
      larger increases in postoperative A-a oxygen gradient and shunt, was unable to
      prevent postoperative decreases in lung compliance, and prolonged extubation
      time, which indicate that use of the drug may hinder early tracheal extubation in
      patients after cardiac surgery. IMPLICATIONS: Traditionally, methylprednisolone
      has been administered to patients undergoing cardiac surgery to decrease
      postoperative pulmonary dysfunction. This study revealed that the drug is
      associated with larger increases in postoperative alveolar-arterial oxygen
      gradient and shunt and prolonged tracheal extubation time in patients undergoing
      coronary artery bypass grafting, which indicate that use of the drug may hinder
      early tracheal extubation.

PMID- 9661541
TI  - Detection of graft nonfunction after liver transplantation by assessment of
      indocyanine green kinetics.

PMID- 9661542
TI  - Warming intravenous fluids reduces perioperative hypothermia in women undergoing
      ambulatory gynecological surgery.
AB  - We evaluated whether warming i.v. fluids resulted in less hypothermia (core
      temperature < 35.5 degrees C) compared with room-temperature fluids. Thirty-eight
      adult outpatients undergoing elective gynecological surgery of > 30 min were
      randomized to two groups: fluid warming at 42 degrees C or control (room
      temperature fluids at approximately 21 degrees C). All patients received general
      anesthesia with isoflurane, tracheal intubation, standard operating room blankets
      and surgical drapes, and passive humidification of inspired gases. Tympanic
      membrane (core) temperatures were measured at baseline and at 15-min intervals
      after induction. The incidence of shivering and postoperative requirement for
      meperidine and/or radiant heat were evaluated. Core temperatures were lower in
      the control compared with the warm fluid group at the end of surgery (35.6 +/-
      0.1 degrees C vs 36.2 +/- 0.1 degrees C; P < 0.05). More patients had final core
      temperature < 35.5 degrees C in the control compared with the warm fluid group
      (35% vs 0%; P < 0.05). There were no differences in time to discharge from the
      postanesthesia care unit or the incidence of shivering between the groups. We
      conclude that fluid warming, in conjunction with standard heat conservation
      measures, was effective in maintaining normothermia during outpatient
      gynecological surgery; however, there was no improvement in patient outcome.
      IMPLICATIONS: Women who received i.v. fluid at body temperature had significantly
      higher core temperatures during and after outpatient gynecological surgery
      compared with women who received i.v. fluids at the temperature of the operating
      room.

PMID- 9661543
TI  - Medial canthus single-injection episcleral (sub-tenon anesthesia): computed
      tomography imaging.
AB  - Single-injection medial canthus periocular anesthesia is a promising regional
      anesthesia technique for ophthalmic surgery. The purpose of this computed
      tomography (CT) study was to confirm that this technique is an episcleral
      injection and to explain why it provides a good akinesia of the globe. Four fresh
      nonpreserved cadavers (eight eyes) were injected with fractioned various volumes
      of a contrast media using a previously described technique. For each injection
      and each eye, CT scans were performed in three planes of the space, and the site
      and spread of the injection was observed. We confirm that single-injection medial
      canthus periocular anesthesia is, in fact, an episcleral anesthesia, which
      explains the good sensory block of the globe. When larger volumes are injected,
      the contrast media spreads to the lids and extraocular muscle sheaths. We believe
      that this may explain why this technique provides good sensory and motor block of
      the globe and eyelids. This technique is a promising alternative to both retro-
      and peribulbar anesthesia. IMPLICATIONS: We describe medial canthus single
      injection periocular anesthesia by a computed tomography injection study in eight
      human cadaver eyes. It was confirmed to be an episcleral injection. Akinesia of
      the eyeball is provided by spreading of the local anesthetic solution from the
      episcleral space to the rectus muscle sheaths.

PMID- 9661544
TI  - The effects of inhaled nitric oxide on postoperative pulmonary hypertension in
      infants and children undergoing surgical repair of congenital heart disease.
AB  - The role of inhaled nitric oxide in the immediate post-bypass period after
      surgical repair of congenital heart disease is uncertain. In a controlled,
      randomized, double-blind study, we tested the hypothesis that inhaled nitric
      oxide (NO) would reduce pulmonary hypertension immediately after surgical repair
      of congenital heart disease in 40 patients with preoperative evidence of
      pulmonary hypertension (mean pulmonary arterial pressure [MPAP] exceeding 50% of
      mean systemic arterial pressure [MSAP]). Patients were then followed in the
      intensive care unit (ICU) to document the incidence of severe pulmonary
      hypertension. Of the patients, 36% (n = 13) emerged from bypass with MPAP > 50%
      MSAP. In these patients, inhaled NO reduced MPAP by 19% (P = 0.008) versus an
      increase of 9% in the placebo group. No effect on MPAP was observed in patients
      emerging from bypass without pulmonary hypertension (n = 23). Inhaled NO was
      required five times in the ICU, always in the patients who had emerged from
      cardiopulmonary bypass with pulmonary hypertension (5 of 13 [38%] versus 0 of
      23). We conclude that, in infants and children undergoing congenital heart
      surgery, inhaled NO selectively reduces MPAP in patients who emerge from
      cardiopulmonary bypass with pulmonary hypertension and has no effect on those who
      emerge without it. IMPLICATIONS: In a randomized double-blind study, inhaled
      nitric oxide selectively reduced pulmonary artery pressures in pediatric patients
      who developed pulmonary hypertension (high blood pressure in the lungs)
      immediately after cardiopulmonary bypass and surgical repair.

PMID- 9661545
TI  - Preemptive caudal bupivacaine and morphine for postoperative analgesia in
      children.
AB  - We designed this double-blind study to evaluate the efficacy of preemptive
      epidural bupivacaine and small-dose morphine for postoperative analgesia in
      children after herniorraphy. Sixty children, ASA physical status I or II, who
      were undergoing elective hernia repair under general anesthesia were randomly
      allocated into two groups. Group I (preemptive group) received 0.66 mL/kg 0.25%
      bupivacaine with morphine 0.02 mg/kg caudally after the induction of anesthesia
      but 15 min before surgery. Group II (postincisional group) received the same drug
      mixture after surgery. Pain was assessed using an objective pain scale (OPS).
      Time to first postoperative analgesics (TFA), the number of supplementary
      analgesic used, and the amount of morphine consumed over the ensuing 24-h period
      were noted. The OPS score was significantly less in Group I at 0.5, 4, and 8 h (P
      < 0.05) than in Group II after surgery. The median OPS score recorded over 24 h
      was 0 for Group I and 2 for Group II, which was significantly different (P <
      0.05). The TFA in Group I (12.55 +/- 3.06 h) was significantly (P < 0.05)
      prolonged compared with Group II (10.62 +/- 3.18 h). The total postoperative
      morphine consumption in Group I (2.24 +/- 1.4 mg) was significantly (P < 0.05)
      less than that in Group II (3.34 +/- 2.29 mg). Nevertheless, the incidence of
      nausea and vomiting was not significantly different between the groups. In this
      study, we demonstrated that preemptive epidural bupivacaine and small-dose
      morphine administration is superior to the same mixture given at the conclusion
      of surgery for pain relief. IMPLICATIONS: This study was performed on two groups
      of 30 children undergoing hernia repair. Group I received a bupivacaine-morphine
      mixture caudally before surgery, and Group II received the same drugs caudally at
      the completion of surgery. Postoperative assessment demonstrated longer and
      better pain relief in Group I.

PMID- 9661546
TI  - The effect of preoperative dexamethasone on the immediate and delayed
      postoperative morbidity in children undergoing adenotonsillectomy.
AB  - In this prospective, randomized, double-blind, placebo-controlled study, we
      examined the effect of preoperative dexamethasone on postoperative nausea and
      vomiting (PONV) and 24-h recovery in children undergoing tonsillectomy. One
      hundred thirty children, 2-12 yr of age, ASA physical status I or II, completed
      the study. All children received oral midazolam 0.5-0.6 mg/kg preoperatively.
      Anesthesia was induced with halothane and nitrous oxide in 60% oxygen and
      maintained with nitrous oxide and isoflurane. Intubation was facilitated by
      mivacurium 0.2 mg/kg. Each child received fentanyl 1 microgram/kg i.v. before
      initiation of surgery, as well as dexamethasone 1 mg/kg (maximal dose 25 mg)
      (steroid group) or an equal volume of saline (control group). Intraoperative
      fluids were standardized to 25-30 mL/kg lactated Ringer's solution. All
      tonsillectomies were performed under the supervision of one attending surgeon
      using an electrodissection technique. Postoperatively, fentanyl and acetaminophen
      with codeine elixir were administered as needed for pain. Rescue antiemetics were
      administered when a child experienced two episodes of retching and/or vomiting.
      Before home discharge, the incidence of PONV, need for rescue antiemetics,
      quality or oral intake, and analgesic requirements did not differ between groups.
      However, during the 24 h after discharge, more patients in the control group
      experienced PONV (62% vs 24% in the steroid group) and complained of poor oral
      intake. Additionally, more children in the control group (8% vs 0% in the steroid
      group) returned to the hospital for the management of PONV and/or poor oral
      intake. The preoperative administration of dexamethasone significantly decreased
      the incidence of PONV over the 24 h after home discharge in these children.
      IMPLICATIONS: In this double blind, placebo-controlled study, we examined the
      efficacy of a single large dose (1 mg/kg; maximal dose 25 mg) of preoperative
      dexamethasone on posttonsillectomy postoperative nausea and vomiting (PONV) in
      children 2-12 yr of age undergoing tonsillectomy. Compared with placebo,
      dexamethasone significantly decreased the incidence of PONV in the 24 h after
      discharge, improved oral intake, decreased the frequency of parental phone calls,
      and resulted in no hospital returns for the management of PONV and/or poor oral
      intake.

PMID- 9661547
TI  - Overnight hospitalization after radical prostatectomy: the impact of two clinical
      pathways on patient satisfaction, length of hospitalization, and morbidity.
AB  - Changes in health care have prompted efforts to reduce length of hospitalization
      while maintaining quality care. Therefore, we evaluated short-term outcomes after
      radical retropubic prostatectomy on 100 consecutive men undergoing surgery for
      clinically localized prostate cancer performed under epidural anesthesia followed
      by epidural morphine or combined with spinal anesthesia using bupivacaine and
      fentanyl (25 micrograms) and followed by i.m. methadone (10-20 mg). All patients
      received oral acetaminophen and ibuprofen beginning 4 h after surgery. Length of
      hospital stay, responses to written satisfaction survey, postoperative morbidity
      and readmission to the hospital were recorded. Using either pathway, 83% of the
      patients were discharged after one night in the hospital. The mean hospital stay
      was 1.34 +/- 1.10 and 1.28 +/- 1.0 days, respectively. Although three men were
      rehospitalized, it was not because of the early discharge. More than 95% of
      patients were satisfied with pain control, and patients discharged after one
      night were not more likely to be dissatisfied than patients hospitalized longer.
      IMPLICATIONS: Both clinical pathways provide excellent anesthesia and analgesia
      and allow discharge 1 day after radical retropubic prostatectomy. Shortened
      hospital stay does not increase patient dissatisfaction or add to postoperative
      morbidity. Patients undergoing other pelvic and abdominal operations may also
      derive similar benefits using these pathways.

PMID- 9661548
TI  - The effect of fentanyl on electrophysiologic recovery of CA 1 pyramidal cells
      from anoxia in the rat hippocampal slice.
AB  - Fentanyl is widely used in conditions in which the brain is at risk of ischemic
      or anoxic injury. We evaluated the effect of fentanyl on anoxic injury to CA 1
      pyramidal cells in the rat hippocampus. These neurons are extremely sensitive to
      anoxic injury and are densely populated with opioid receptors. We prepared
      hippocampal slices from adult Sprague-Dawley rats and evoked a postsynaptic
      population spike in the CA 1 pyramidal cell region by stimulating the Schaffer
      collateral pathway. The amplitude of this response was used to evaluate the
      effect of fentanyl on anoxic injury. Pretreatment with fentanyl (50 or 500 ng/mL)
      did not alter the amplitude of the CA 1 population spike before anoxia, nor did
      it alter the recovery of this response after 5,6, or 7 min of anoxia. After 5 min
      of anoxia, the population spike recovered to 76% of its preanoxic level in the
      control group and to 87% in the group treated with 500 ng/mL of fentanyl. After 6
      min of anoxia, recovery was 45% in the control group, 57% in the group treated
      with 50 ng/mL of fentanyl, and 58% in the group treated with 500 ng/mL of
      fentanyl. After 7 min of anoxia, recovery was 5% in the control group and 4% in
      the group treated with 50 ng/mL of fentanyl. We conclude that fentanyl does not
      affect the recovery of the electrophysiological response in rat hippocampal
      neurons subjected to an anoxic insult. IMPLICATIONS: Because fentanyl is used in
      large doses during surgical procedures in which the brain is at increased risk of
      ischemic or anoxic injury, it is important to determine its effect on such
      injury. Using the rat hippocampal slice model, we found fentanyl to be neither
      neurotoxic nor protective against anoxic injury to neurons when used in
      concentrations comparable to those produced in clinical practice.

PMID- 9661549
TI  - Relative neuroprotective effects of dizocilpine and isoflurane during focal
      cerebral ischemia in the rat.
AB  - Both dizocilpine (MK-801) and isoflurane antagonize glutamatergic
      neurotransmission. In this study, we examined the relative neuroprotective
      effects of these drugs administered in equianesthetic doses before the onset of
      focal cerebral ischemia. Rats were anesthetized with 1.0%-1.5% isoflurane and
      surgically prepared for filament occlusion of the middle cerebral artery (MCAO).
      After preparation, one group (n = 22) remained anesthetized with 0.7% isoflurane.
      Another group (n = 18) was given dizocilpine (1 mg/kg intraperitoneally), and
      isoflurane was discontinued. The third group (n = 18) was allowed to awaken
      immediately after the onset of ischemia. MCAO persisted for 75 min. Epidural
      temperature was controlled at 37.5 degrees C during ischemia and the first 22 h
      of recovery. A 7-day recovery interval was allowed. Total infarction volumes
      (mean +/- SD) were less for the dizocilpine group (100 +/- 65 mm3) versus the
      awake group (182 +/- 36 mm3; P = 0.001). Infarction volumes did not differ
      significantly between the isoflurane group (142 +/- 81 mm3) and either the
      dizocilpine (P = 0.11) or the awake group (P = 0.15). Isoflurane was examined at
      doses used clinically but smaller than those found to reduce N-methyl-D-aspartate
      (NMDA)-mediated injury in vitro. This study supports the hypothesis that NMDA
      receptor activation is injurious during focal ischemia and that amelioration of
      focal ischemic brain damage by NMDA receptor antagonists persists under
      normothermic conditions. IMPLICATIONS: Rats underwent focal cerebral ischemia
      with rigid maintenance of brain normothermia. The glutamate receptor antagonist
      dizocilpine was effective in reducing cerebral infarction size during persistent
      conditions of brain normothermia. In contrast, isoflurane administered at
      equianesthetic doses did not reduce infarction size. This study supports the
      hypothesis that N-methyl-D-aspartate receptor activation is injurious during
      focal ischemia and that amelioration of focal ischemic brain damage by N-methyl-D
      aspartate receptor antagonists persists under normothermic conditions.

PMID- 9661550
TI  - Lateral approach to the sciatic nerve in the popliteal fossa.
AB  - We describe a modification of the sciatic nerve (SN) block in the popliteal fossa
      through the lateral approach. After a brief anatomic study using previously
      reported landmarks, we propose a new needle orientation associated with a double
      injection technique after identification of the tibial and the common peroneal
      nerve. Thirty-four patients undergoing ankle or foot surgery were enrolled in
      this study. With patients in the supine position, the upper edge of the patella
      and the groove between the posterior border of the vastus lateralis and the
      anterior border of the tendon of the biceps femoris were identified. The needle
      was directed posteriorly with a 20-30 degrees angle relative to the horizontal
      plane and slightly caudal. Both nerves were individually located with a nerve
      stimulator and blocked with a mixture of lidocaine-bupivacaine and clonidine. In
      all but one case, the two nerves were easily located, and no vascular puncture
      was evident. Effective analgesia was obtained for a minimum of 15 h (first
      analgesic demand). We conclude that this technique, with a modified direction of
      the needle and a double stimulation, provides a very high rate of success for SN
      blockade in the popliteal fossa. IMPLICATIONS: We describe a new lateral approach
      to the sciatic nerve in the popliteal fossa. The needle was directed caudad and
      posteriorly while seeking with a nerve stimulator for the tibial and the peroneal
      nerves, which were blocked separately. This technique was very successful.

PMID- 9661551
TI  - Assessing the level of regional blockade under general anesthesia using the skin
      vasomotor reflex test.
AB  - We investigated whether skin vasomotor reflex (SVmR) testing can be used to
      assess the sensory blockade level under light general anesthesia. In 15 patients
      scheduled for abdominal gynecological surgery, the SVmR was tested under inhaled
      isoflurane or sevoflurane (0.5%-0.6%) with nitrous oxide (50%). Seven minutes
      after the epidural injection (5-10 mL of 2% lidocaine), a tetanic electrical
      stimulus (20 mA, 2 s) was applied to the skin and repeated sequentially from the
      L3 dermatome in the cephalad direction. Changes in the laser Doppler skin blood
      flow on the index finger tip were assessed for the SVmR. If there was a positive
      response, SVmR testing was discontinued. The relationship between the uppermost
      dermatome of the negative SVmR response and the intraoperative effectiveness of
      the epidural block was determined. In 11 patients, we confirmed a clear boundary
      of skin dermatome by the SVmR test. The uppermost dermatome of the negative SVmR
      response at higher than the T7 level was necessary to maintain the combined
      epidural and light general anesthesia for the transabdominal gynecological
      surgery (P = 0.002). We conclude that SVmR testing is useful in estimating the
      blockade level of regional anesthesia under light general anesthesia.
      IMPLICATIONS: Considering "preemptive analgesia," a complete sensory blockade
      should be established before a skin incision. In 11 of 15 patients under
      epidural/ general anesthesia, we confirmed a clear dermatome boundary using the
      skin vasomotor reflex test. This test could be an indicator for estimating the
      sensory blockade level of patients under general anesthesia.

PMID- 9661552
TI  - Effects of intravenous patient-controlled analgesia with morphine, continuous
      epidural analgesia, and continuous three-in-one block on postoperative pain and
      knee rehabilitation after unilateral total knee arthroplasty.
AB  - In this study, we assessed the influence of three analgesic techniques on
      postoperative knee rehabilitation after total knee arthroplasty (TKA). Forty-five
      patients scheduled for elective TKA under general anesthesia were randomly
      divided into three groups. Postoperative analgesia was provided with i.v. patient
      controlled analgesia (PCA) with morphine in Group A, continuous 3-in-1 block in
      Group B, and epidural analgesia in Group C. Immediately after surgery, the three
      groups started identical physical therapy regimens. Pain scores, supplemental
      analgesia, side effects, degree of maximal knee flexion, day of first walk, and
      duration of hospital stay were recorded. Patients in Groups B and C reported
      significantly lower pain scores than those in Group A. Supplemental analgesia was
      comparable in the three groups. Compared with Groups A and C, a significantly
      lower incidence of side effects was noted in Group B. Significantly better knee
      flexion (until 6 wk after surgery), faster ambulation, and shorter hospital stay
      were noted in Groups B and C. However, these benefits did not affect outcome at 3
      mo. We conclude that, after TKA, continuous 3-in-1 block and epidural analgesia
      provide better pain relief and faster knee rehabilitation than i.v. PCA with
      morphine. Because it induces fewer side effects, continuous 3-in-1 block should
      be considered the technique of choice. IMPLICATIONS: In this study, we determined
      that, after total knee arthroplasty, loco-regional analgesic techniques (epidural
      analgesia or continuous 3-in-1 block) provide better pain relief and faster
      postoperative knee rehabilitation than i.v. patient-controlled analgesia with
      morphine. Because it causes fewer side effects than epidural analgesia,
      continuous 3-in-1 block is the technique of choice.

PMID- 9661553
TI  - Peripheral nerve blocks improve analgesia after total knee replacement surgery.
AB  - Total knee replacement (TKR) produces severe postoperative pain. Peripheral nerve
      blocks can be used as analgesic adjuncts for TKR, but the efficacy of femoral
      nerve blocks alone is controversial. The sciatic nerve innervates posterior
      regions of the knee; thus, performance of both sciatic and femoral nerve blocks
      may be necessary to improve analgesia after TKR. We performed this study to
      determine whether peripheral nerve blocks improve analgesia after TKR. In a
      randomized, double-blind fashion, 36 patients undergoing TKR received either
      femoral, sciatic-femoral, or sham nerve blocks after a standardized spinal
      anesthetic. Further postoperative analgesia was provided by patient-controlled
      i.v. morphine and ketorolac. Pain at rest and with physical therapy, morphine
      use, nausea, pruritus, sedation, and patient satisfaction were assessed. Patients
      receiving peripheral nerve blocks reported better analgesia at rest for at least
      8 h after transfer to the hospital ward (P < 0.05). Morphine use was decreased by
      approximately 50% in the peripheral nerve block groups until the second
      postoperative day (P < 0.02). Side effect profiles and patient satisfaction were
      similar between groups. We conclude that femoral nerve blocks improve analgesia
      and decrease morphine use after TKR. The addition of a sciatic nerve block to the
      femoral nerve block did not further improve analgesic efficacy. IMPLICATIONS:
      Performance of femoral nerve blocks improves analgesia and decreases the need for
      morphine after total knee replacement surgery. The addition of a sciatic nerve
      block to the femoral nerve block does not provide additional benefits.

PMID- 9661554
TI  - Dose-response of ketorolac as an adjunct to patient-controlled analgesia morphine
      in patients after spinal fusion surgery.
AB  - This randomized, blind study was designed to determine the appropriate dose of
      ketorolac (a drug used as a supplement to opioids) to administer to patients who
      have undergone spinal stabilization surgery. The ketorolac was administered every
      6 h, in addition to patient-controlled analgesia (PCA) with morphine, to 70
      inpatients undergoing spine stabilization by one surgeon. The study was performed
      to determine the analgesic efficacy and incidence of side effects with different
      doses of ketorolac. The patients were divided into seven groups. They were given
      either i.v. saline (control group) or i.v. ketorolac (5, 7.5, 10, 12.5, 15, or 30
      mg) every 6 h. The outcomes measured included pain scores, 24-h morphine usage,
      level of sedation, and side effect profile six times during the first 24 h
      postoperatively. The total dose of morphine was significantly larger in the
      control and 5 mg ketorolac groups than in the other five groups. Morphine
      consumption was similar in all groups receiving > or = 7.5 mg of ketorolac. The
      pain scores were significantly higher in the control group than in some of the
      larger dose groups at three of the study intervals. The 5 mg group had higher
      pain scores than the other groups at most of the time intervals studied. There
      were no significant differences in pain scores among the other five groups.
      Sedation scores were higher (i.e., patients were more sedated) in the control
      group than in the other six groups at three of the time periods. We conclude that
      the administration of ketorolac 7.5 mg every 6 h has a morphine-sparing effect
      equivalent to that of larger doses in patients undergoing spine stabilization
      surgery. Using larger doses of ketorolac did not result in less somnolence, lower
      morphine use, or less pain. We recommend that ketorolac 7.5 mg be given every 6 h
      to patients undergoing spinal fusion surgery in addition to PCA morphine.
      IMPLICATIONS: Using smaller doses of ketorolac (e.g., 7.5 mg every 6 h) as a
      supplement to morphine patient-controlled analgesia is as effective as larger
      doses in patients who have undergone spine stabilization surgery.

PMID- 9661555
TI  - Preoperative epidural ketamine does not have a postoperative opioid sparing
      effect.
AB  - Ketamine reduces nociception by binding noncompetitively to the N-methyl-D
      aspartate receptor, the activation of which provokes hypersensitivity within the
      central nervous system. We studied the analgesic effect of extradural ketamine
      given before or after upper abdominal surgery. We sought to assess the effect of
      ketamine on preemptive analgesia. Ketamine 60 mg was injected epidurally through
      an indwelling catheter that was inserted at the T7-8 or T8-9 interspace in 98
      patients. Patients were randomly allocated into one of the two groups, each
      consisting of 49 patients: ketamine was given before the induction of anesthesia
      (Group 1) and after the parietal peritoneum was closed (Group 2). Sample size was
      calculated using a two-tailed alpha = 0.05 and power of 95%. For postoperative
      analgesia, meperidine 25 mg was given epidurally whenever a patient complained of
      pain or the visual analog scale score was greater than 4. The first and the
      second day cumulative meperidine consumption was not different between the two
      groups. We conclude that preoperative epidural ketamine 60 mg does not have a
      preemptive analgesic effect. IMPLICATIONS: In patients undergoing upper abdominal
      surgery, a single epidural injection of 60 mg of ketamine administered
      preoperatively was not associated with decreased postoperative analgesic demands.
      This findings does not contribute to one of the fundamental scientific objectives
      of preemptive analgesia that postoperative analgesia well beyond the duration of
      any single drug effect could be produced.

PMID- 9661556
TI  - Clonidine added to the anesthetic solution enhances analgesia and improves
      oxygenation after intercostal nerve block for thoracotomy.
AB  - We evaluated the effect of adding clonidine to bupivacaine on postoperative pain
      control and oxygenation after intercostal nerve blockade (ICB) for thoracotomy,
      and attempted to distinguish a systemic from a local effect of clonidine. ICB
      with 2 mg/kg 0.5% bupivacaine was performed in 36 patients undergoing
      thoracotomy. Patients were randomized to one of three groups: 1) a control group
      that received bupivacaine with saline for ICB and an IM injection of saline, 2)
      an IM group that received bupivacaine with saline for ICB and an IM injection of
      2 micrograms/kg clonidine, and 3) a block group that received bupivacaine with 2
      micrograms/kg clonidine for ICB and an IM injection of saline. Blood gases,
      visual analog scale (VAS) scores, and analgesic demand were determined hourly for
      8 h after arrival in the postoperative care unit (PCU). Patients in the block
      group had significantly lower VAS scores, higher arterial oxygen tension, and
      lower analgesic demand for the first 4 h in the PCU, compared with the two other
      groups. No difference was noted thereafter. We conclude that the addition of
      clonidine to bupivacaine for ICB leads to a short-term effect enhancing
      postoperative pain control and improving arterial oxygenation, probably mediated
      by a direct effect on the nerves. IMPLICATIONS: Severe pain after thoracotomy can
      lead to impaired ventilation. We studied the effect of adding clonidine to
      bupivacaine for intercostal nerve blockade after thoracotomy. Clonidine
      administered directly on the nerves enhanced analgesia and improved oxygenation
      for a short time compared with systemic administration or control.

PMID- 9661557
TI  - Comparison of plasma lidocaine concentrations after injection of a fixed small
      volume in the stellate ganglion, the lumbar epidural space, or a single
      intercostal nerve.
AB  - We measured the plasma lidocaine concentrations after stellate ganglion block
      (SGB) and compared them with those after intercostal nerve block (ICNB) and
      epidural block (EB) using identical doses of lidocaine. Thirty patients
      undergoing SGB (n = 10), ICNB (n = 10), or EB (n = 10) in our pain clinic
      participated in this study. Six milliliters of 1% lidocaine was used for all
      nerve blocks. SGB was performed at the C6 transverse process, ICNB was performed
      on a single intercostal nerve, and epidural lidocaine was injected through the
      lumbar epidural catheter. After drug administration, venous blood samples were
      taken from an indwelling catheter in the arm every minute for the first 10 min
      and 15, 20, 30, 45, and 60 min thereafter. Plasma lidocaine concentrations were
      measured by using an enzyme immunoassay method. The SGB group showed
      significantly higher peak plasma lidocaine concentrations than other groups (SGB
      1.65 +/- 0.21 microgram/mL, ICNB 0.89 +/- 0.12 microgram/mL, EB 0.91 +/- 0.19
      microgram/mL; P < 0.01). The SGB group reached peak levels significantly faster
      than the other groups (SGB 3.4 +/- 1.0 min, ICNB 7.9 +/- 1.5 min, EB 6.9 +/- 0.7
      min; P < 0.01). We conclude that the plasma lidocaine concentrations after SGB
      were higher than those after ICNB and EB when using small, equal doses of
      lidocaine. The high and rapid peak plasma lidocaine concentrations after SGB are
      probably related to the high vascularity of the injection site. IMPLICATIONS:
      Higher plasma concentrations of local anesthetics are reportedly obtained after
      multiple intercostal nerves blocks compared with those after other types of nerve
      blocks. Our results, however, showed that the peak plasma concentrations after
      stellate ganglion block were higher and faster than those after a single
      intercostal nerve block.

PMID- 9661558
TI  - Methicillin-resistant Staphylococcus aureus sepsis resulting from infection in
      paravertebral muscle after continuous epidural infusion for pain control in a
      patient with herpes zoster.

PMID- 9661559
TI  - Epidural labor analgesia and the incidence of cesarean delivery for dystocia.
AB  - We performed this retrospective study to examine the changes in cesarean delivery
      rates associated with the establishment of a labor epidural service. In April
      1993, St. Louis Regional Medical Center established an on-demand labor epidural
      service. We obtained demographic data for all patients and reviewed the operative
      records of all patients undergoing cesarean section who delivered 12 mo before
      and 16 mo after the start of the labor epidural service. We compared labor
      epidural rates and total and nulliparous dystocia cesarean delivery rates before
      and after the epidural service started and among patients who did and did not
      receive labor epidural analgesia when it was available. Included were 3195
      patients who delivered before and 3733 patients who delivered after epidural
      analgesia became available. Labor epidural rates were 1.2% vs 29.4% for the
      Before group versus the After group (P < 0.001). Total (9.1% vs 9.7%) and
      nulliparous dystocia (5.7% vs 6.4%) cesarean delivery rates did not significantly
      change with the availability of epidural analgesia. However, the total (11.6% vs
      8.8%; P = 0.009) and dystocia (8.0% vs 1.0%; P = 0.001) cesarean delivery rates
      were higher among patients who received epidural analgesia when it was available.
      We conclude that epidural labor analgesia is associated with, but does not cause,
      cesarean delivery for dystocia. IMPLICATIONS: Increased epidural analgesia use
      did not change the overall dystocia cesarean delivery rate, although dystocia was
      more common among women who chose an epidural analgesia. Consequently, limiting
      epidural availability will not affect cesarean delivery rates. The evidence does
      not support advising patients that epidural labor analgesia increases the risk of
      cesarean delivery.

PMID- 9661560
TI  - Atypical presentation of amniotic fluid embolism.

PMID- 9661561
TI  - Reactive oxygen species contribute to oxygen-related lung injury after acid
      aspiration.
AB  - Hyperoxia increases pulmonary damage after acid aspiration. We hypothesize that
      free radicals play a role in acute lung injury. To examine this hypothesis, we
      injured rats by intratracheal instillation of acidic isotonic sodium chloride
      solution (NS) (pH 1.25); NS + gastric particles (particle pH 5.3); or acid +
      particles (pH 1.25). Animals were exposed to 98% oxygen or air for 5 h.
      Superoxide (HO2) generation was measured in either an aliquot of white blood
      cells (WBCs) recovered from bronchoalveolar lavage (BAL) or from blood. Lungs
      were analyzed for thiobarbituric acid-reactive substances (TBARS) and
      carbonylated proteins. The antioxidant capacity was measured using a 2-2'-azo-bis
      amidinopropane hydrochloride neutralizing assay. Generation of HO2 by WBCs in
      peripheral blood was greater in animals exposed to 98% O2 (89.8 +/- 12.5 U. min
      1.10(5) neutrophils) compared with air exposure (37.5 +/- 9.2 U.min-1.10(5)
      neutrophils) after combined injury (P < 0.05). Similarly, HO2 generation by WBCs
      retrieved from BAL was higher in oxygen-exposed rats (987.74 +/- 128 U.min
      1.10(5) WBC) compared with air-exposed animals after an identical injury (348 +/-
      9.2 U. min-1.10(5) WBC) (P < 0.05). TBARS and carbonylated protein levels in the
      lungs of oxygen-exposed animals (587.9 +/- 58.6 and 55.8 +/- 3.1 pmol/mg of
      protein, respectively) were higher than those in air-exposed rats after combined
      injury (342.8 +/- 15.1 and 28.6 +/- 4.6 pmol/mg of protein, respectively) and
      compared with air-exposed uninjured rats (340.6 +/- 9.8 and 18.3 +/- 2.8 pmol/mg
      of protein, respectively; P < 0.01). Antioxidant capacity decreased in acid and
      combined injury groups (2.41 +/- 0.13 min and 1.94 +/- 0.15 min, respectively)
      compared with the uninjured group after 5 h of exposure to 98% oxygen (4.85 +/-
      0.19 min; P < 0.01). We demonstrated evidence of increased oxidant activity on
      lipids and proteins in injured lungs after oxygen exposure. The decrease in
      antioxidant capacity after low pH aspiration with exposure to hyperoxia may
      contribute to this increase. IMPLICATIONS: Oxygen administration results in a
      lung pathology known as oxygen toxicity. This effect is usually not significant
      if the duration of exposure is limited to < 24 h. In the presence of acute
      inflammatory lung injury, exposure to hyperoxia results in lung damage in a
      shorter time. We demonstrate that sufficiently decreased lung antioxidant reserve
      capacity may be accountable for this early toxicity.

PMID- 9661562
TI  - Gastrointestinal monitoring using measurement of intramucosal PCO2.

PMID- 9661563
TI  - The placement of the cuffed oropharyngeal airway with sevoflurane in adults: a
      comparison with the laryngeal mask airway.
AB  - We sought to determine the anesthetic duration of sevoflurane required to achieve
      good conditions for placement of a cuffed oropharyngeal airway (COPA) or a
      laryngeal mask airway (LMA). Forty adult ASA physical status I or II patients
      presenting for elective surgery received single-breath vital capacity inhaled
      induction with 5% sevoflurane via face mask; thereafter, ventilation was manually
      assisted. The patients were randomized to receive either a COPA or LMA placement.
      The time of anesthetic exposure was varied for consecutive patients using the
      staircase method. The mean (95% confidence interval) anesthetic time required for
      acceptable COPA placement (100 [55-145] s) was significantly shorter than that
      for LMA (160 [101-219] s). The 50% and 95% effective doses (from logistic
      analyses) for acceptable conditions associated with COPA or LMA placement were 90
      s and 145 s or 164 s and 261 s, respectively. These findings suggest that COPA
      insertion is less stimulating than the LMA. IMPLICATIONS: The cuffed
      oropharyngeal airway is a new airway device that is similar to a laryngeal mask
      airway in many ways. However, it requires shorter anesthetic duration for
      successful placement, which suggests that it can be placed with less stimulation.
      It may be an alternative to a laryngeal mask airway.

PMID- 9661564
TI  - A comparison of the laryngeal mask airway and cuffed oropharyngeal airway in
      anesthetized adult patients.
AB  - We compared the cuffed oropharyngeal airway (COPA) with the laryngeal mask airway
      (LMA) in 120 anesthetized adult patients. We compared 1) placement success rates,
      2) airway interventional requirements, 3) airway stability in different head/neck
      positions, 4) cardiorespiratory tolerance, and 5) intra- and postoperative
      adverse events/symptoms. A standardized anesthesia protocol was followed by four
      anesthesiologists experienced with both devices. Observational data were
      validated by independent analysis of continuous video recordings. Postoperative
      interviews were double-blind to the device used. The LMA had a more frequent
      success rate than COPA (97% vs 55%, P < 0.00001), an overall higher success rate
      (100% vs 83%; P = 0.001), a shorter time to achieve an effective airway (49 vs
      188 s; P < 0.00001), a higher oropharyngeal leak pressure (21 vs 16 cm H2O; P =
      0.003), and a fewer number of chin lift airway interventions required (0.1% vs
      42%; P < 0.00001). When comparing mean tidal volumes in different head/neck
      positions to assess airway stability, the quality of airway was unchanged in 98%
      patients with the LMA and 54% with the COPA (P < 0.00001). The incidences of
      intraoperative adverse events were similar. On removal, blood was detected more
      often on the COPA (3% vs 14%; P = 0.04). In the late postoperative period, more
      patients complained of adverse symptoms with the COPA than with the LMA (26% vs
      57%; P = 0.001). Late postoperative symptoms occurred more frequently with the
      COPA (0.87 vs 0.34; P = 0.003). There was more late postoperative sore throat
      (14% vs 36%; P = 0.0003) and more jaw/neck pain (12% vs 26%; P = 0.0008) in
      patients managed with the COPA. This study demonstrates that the LMA offers
      advantages over the COPA in most technical aspects of airway management and in
      terms of postoperative morbidity. IMPLICATIONS: In this randomized, prospective
      study, we compared the laryngeal mask airway and the cuffed oropharyngeal airway
      in anesthetized patients. The laryngeal mask airway offers advantages in most
      technical aspects of airway management and in terms of postoperative morbidity.

PMID- 9661565
TI  - Practice patterns in managing the difficult airway by anesthesiologists in the
      United States.
AB  - Despite the availability of several techniques and devices for the management of
      the difficult airway, little information has been published regarding the
      prevalence of their use by anesthesiologists in the United States. To determine
      current practice patterns, we surveyed clinicians using a questionnaire
      consisting of 14 difficult airway scenarios. Anesthesiologists were requested to
      indicate their likely approach to anesthetic induction (e.g., awake but sedated,
      general anesthesia with spontaneous ventilation, general anesthesia with apnea
      after assuring a patent airway, or general anesthesia with apnea) and the primary
      device they would use to intubate (e.g., direct laryngoscopy [DL], flexible
      fiberoptic bronchoscope [FOB], rigid fiberoptic device, surgical airway,
      retrograde intubation kit, laryngeal mask airway, gum elastic bougie, or
      Combitube). The availability of these devices was also determined (in room at all
      times, available "stat," available if arranged preoperatively, or not available).
      The survey was mailed to 1000 randomly chosen active members of the American
      Society of Anesthesiologists. Second and third surveys were mailed to non
      responders. Four hundred seventy-two completed surveys were returned. Responses
      by demographic groups were compared by using chi 2 analysis. DL and FOB-aided
      tracheal intubation techniques were chosen for most cases by most
      anesthesiologists (P < 0.05). Anesthesiologists with > 10 yr of clinical
      experience and those older than 55 yr of age preferred DL with apneic conditions
      (P < 0.05). Anesthesiologists who had attended workshops within the last 5 yr had
      greater availability of retrograde guidewire equipment and FOBs (P < 0.05). There
      was little use of newer alternative airway devices. IMPLICATIONS: Although the
      teaching of alternative methods of securing a difficult airway has become
      ubiquitous, most anesthesiologists rely on direct laryngoscopy and fiberoptic
      aided intubation in most clinical circumstances. Although workshops in the
      management of the difficult airway may have resulted in increased use of the
      fiberoptic bronchoscope and the availability of retrograde guidewire intubation
      equipment, other devices have not enjoyed such an increase.

PMID- 9661566
TI  - Predicting the size of a double-lumen endobronchial tube based on tracheal
      diameter.
AB  - We assessed whether using the tracheal diameter to predict the correct size of
      the left double-lumen endobronchial tube (DLT) could be used for our generally
      smaller sized Asian patients. Sixty-six consecutive adult patients under
      anesthesia for elective surgery requiring the use of a DLT were studied. The size
      of the left-sided DLT used was based on the width of patients' trachea measured
      from the preoperative posterior-anterior chest radiograph. The placement of the
      DLT was standardized and confirmed with fiberoptic bronchoscopy. The correct size
      of the DLT was the largest size tube inserted into the left bronchus with a small
      air leak detectable when the endobronchial cuff was deflated but not exceeding
      the recommended resting volume when inflated for lung isolation. Using this
      method of choosing our DLT, we found that an oversized DLT was often chosen
      especially among our female Asian patients. The overall positive predictive
      values for the male and female patients were 77.3% and 45.5%, respectively. We
      postulate that this could be due to our criteria for correct DLT size or that our
      local Asian patients, especially the females, were smaller and shorter.
      IMPLICATIONS: This study assessed whether the correct double-lumen endobronchial
      tube size could be predicted from tracheal diameter measurements taken from the
      chest radiograph. We found that this method of choosing the double-lumen
      endobronchial tubes was not always reliable.

PMID- 9661567
TI  - The effect of clonidine or midazolam premedication on perioperative responses
      during ketamine anesthesia.
AB  - The use of ketamine as a sole anesthetic induces marked central sympathetic
      stimulation, causing increased heart rate, blood pressure (BP), and oxygen
      consumption (VO2). Both alpha 2-agonists and benzodiazepines have been used to
      attenuate these potentially harmful ketamine-induced responses. This double
      blind, randomized, placebo-controlled study was designed to compare the
      perioperative metabolic, hemodynamic, and sympathoadrenal responses to IM
      clonidine (2 micrograms/kg) and midazolam (70 micrograms/kg) premedication during
      ketamine anesthesia. VO2 was measured continuously using indirect calorimetry in
      30 ASA physical status I patients. The patients received ketamine, mivacurium,
      and fentanyl for the induction of anesthesia. Anesthesia was maintained using a
      ketamine infusion and fentanyl boluses i.v. Preoperatively, both VO2 and BP
      decreased significantly after the administration clonidine and midazolam compared
      with placebo (P < 0.01). Intraoperatively, VO2 was higher in the midazolam group
      than in the placebo and clonidine groups (P < 0.05). Postoperatively, there were
      no significant differences in BP and VO2, although they stayed at lower level in
      the clonidine group during the whole postoperative period. Clonidine decreased
      pre- and postoperative plasma catecholamine concentrations (P < 0.05). Our
      results indicate that a midazolam-ketamine combination may induce potentially
      harmful metabolic stimulation, whereas the sympatholytic effects of clonidine on
      ketamine-anesthetized patients may be beneficial, as perioperative VO2 was
      decreased. IMPLICATIONS: Ketamine causes sympathetic stimulation with an ensuing
      increase in oxygen consumption. Anticipating that clonidine might attenuate this
      response, we measured oxygen consumption in patients undergoing surgery during
      ketamine anesthesia. Patients treated with a clonidine-ketamine combination had
      lower intra- and postoperative oxygen consumption than those treated with a
      midazolam-ketamine combination.

PMID- 9661568
TI  - Clonidine does not impair redistribution hypothermia after the induction of
      anesthesia.
AB  - Clonidine is commonly given for premedication, and it impairs normal
      thermoregulatory responses to warm and cold stimuli while depressing sympathetic
      tone. We studied the effect of premedication by clonidine on redistribution
      hypothermia induced by the induction of anesthesia. Sixteen ASA physical status I
      or II patients were randomly assigned to receive either clonidine 150 micrograms
      or a placebo. Anesthesia was induced 45 min later by thiopental, fentanyl, and
      vecuronium i.v. and was maintained by the administration of 0.6% isoflurane. We
      monitored central core (tympanic) temperature and skin surface temperatures at
      the forearm and the fingertip during the 2 h after the induction of anesthesia
      before surgery. We estimated skin blood flow at the level of the forearm by using
      laser Doppler during the same period. The core temperature decreased comparably
      in the two groups of patients, from 37.1 +/- 0.2 degrees C to 35.3 +/- 0.4
      degrees C and from 37.1 +/- 0.2 degrees C to 35.5 +/- 0.3 degrees C in the
      clonidine and placebo groups, respectively. The forearm-fingertip surface
      temperature gradient decreased similarly in the two groups. There was no evidence
      of cutaneous vasoconstriction. The laser Doppler index at the fingertip increased
      similarly in the two groups, as did the forearm-fingertip temperature gradient.
      We conclude that premedication with clonidine does not significantly impair the
      profile of central hypothermia induced by heat redistribution after the induction
      of anesthesia. IMPLICATIONS: The induction of general anesthesia is associated
      with redistribution hypothermia. This study shows that premedication with oral
      clonidine does not worsen the decrease in core temperature resulting from general
      anesthesia.

PMID- 9661569
TI  - Tramadol reduces the sweating, vasoconstriction, and shivering thresholds.
AB  - The analgesic tramadol inhibits the neuronal reuptake of norepinephrine and 5
      hydroxytryptamine, facilitates 5-hydroxytryptamine release, and activates mu
      opioid receptors. Each of these actions is likely to influence thermoregulatory
      control. We therefore tested the hypothesis that tramadol inhibits
      thermoregulatory control. Eight volunteers were evaluated on four study days, on
      which they received no drugs, tramadol 125 mg, tramadol 250 mg, and tramadol 250
      mg with naloxone, respectively. Skin and core temperatures were gradually
      increased until sweating was observed and then decreased until vasoconstriction
      and shivering were detected. The core temperature triggering each response
      defined its threshold. Tramadol decreased the sweating threshold by -1.03 +/-
      0.67 degrees C microgram-1.mL (r2 = 0.90 +/- 0.12). Tramadol also decreased the
      vasoconstriction threshold by -3.0 +/- 4.0 degrees C microgram-1.mL (r2 = 0.94 +/
      0.98) and the shivering threshold by -4.2 +/- 4.0 degrees C microgram-1.mL(r2 =
      0.98 +/- 0.98). The sweating to vasoconstriction interthreshold range nearly
      doubled from 0.3 +/- 0.4 degree C to 0.7 +/- 0.6 degree C during the
      administration of large-dose tramadol (P = 0.04). The addition of naloxone only
      partially reversed the thermoregulatory effects of tramadol. The thermoregulatory
      effects of tramadol thus most resemble those of midazolam, another drug that
      slightly decreases the thresholds triggering all three major autonomic
      thermoregulatory defenses. In this respect, both drugs reduce the "setpoint"
      rather than produce a generalized impairment of thermoregulatory control.
      Nonetheless, tramadol nearly doubled the interthreshold range at a concentration
      near 200 ng/mL. This indicates that tramadol slightly decreases the precision of
      thermoregulatory control in addition to reducing the setpoint. IMPLICATIONS: The
      authors evaluated the effects of the analgesic tramadol on the three major
      thermoregulatory responses: sweating, vasoconstriction, and shivering. Tramadol
      had only slight thermoregulatory effects. Its use is thus unlikely to provoke
      hypothermia or to facilitate fever.

PMID- 9661570
TI  - The efficiency of CO2 elimination during high-frequency jet ventilation for
      laryngeal microsurgery.
AB  - For adequate and safe use of high-frequency jet ventilation (HFJV), reliable
      monitoring of the PCO2 status and course is necessary. Because of improved
      handling and performance, recently available transcutaneous PCO2 monitoring
      devices such as MicroGas 7650 (Kontron Instruments Medical Sensors, Basel,
      Switzerland) should enable more effective surveillance of CO2 elimination and,
      subsequently, better control of subglottic HFJV. Adult patients (n = 164)
      undergoing laryngeal microsurgery during total i.v. anesthesia were assessed. The
      resulting transcutaneous PCO2 values, as well as the necessary driving pressure
      settings, were analyzed to define the CO2 elimination capacity of each patient.
      Therefore, an individual CO2 elimination coefficient (ECCO2) was calculated. The
      frequency distribution of the obtained ECCO2 values showed a normal distribution
      with a median at 0.79 and a range between 0.30 and 2.17. A significant difference
      in the frequency of obstructive lung disease was found between two patient
      subpopulations separated by the 25th percentile at an ECCO2 value of 0.63. Other
      co-factors of CO2 elimination during HFJV were age, gender, and body weight,
      whereas height and ventilation duration were not involved. We conclude that the
      individual assessment of ECCO2 enables one to find adequate ventilator settings,
      resulting in lower airway pressure and less cooling and drying of the
      tracheobronchial mucosa. IMPLICATIONS: CO2 elimination during high-frequency jet
      ventilation can be assessed by calculating the CO2 elimination coefficient
      (ECCO2) of each patient from the required driving pressure and the resulting
      transcutaneous CO2 partial pressure. The frequency distribution of ECCO2 in a
      typical laryngological patient population was analyzed, and a value of 0.63 was
      found to be a characteristic limit between sufficient and difficult CO2
      elimination. The individual assessment of ECCO2 enables one to find adequate
      ventilator settings, resulting in lower airway pressure and less cooling and
      drying of the tracheobronchial mucosa.

PMID- 9661571
TI  - Visual evaluation of residual curarization in anesthetized patients using one
      hundred-hertz, five-second tetanic stimulation at the adductor pollicis muscle.
AB  - We were looking for a clinical test to indicate a train-of-four (TOF) ratio of
      approximately 0.9. We compared the adductor pollicis muscle (AP) visually
      evaluated response to ulnar nerve 100-Hz, 5-s tetanus (RF100 Hz) with the
      measured AP TOF ratio in 30 ASA physical status I or II adult anesthetized
      (propofol, sufentanil, N2O/O2) patients. After the induction of anesthesia, the
      left ulnar nerve was stimulated at the wrist (single twitch and TOF) and the
      resultant isometric force was measured. When TOF was assessed, the independent
      investigators, unaware of the left AP-measured TOF ratios, visually evaluated the
      presence or absence of AP fading elicited by right ulnar nerve 100-Hz, 5-s
      tetanus. The 30 patients were randomly allocated to receive either 0.5 mg/kg
      atracurium (n = 15) or 0.1 mg/kg vecuronium (n = 15). The neuromuscular blockade
      was allowed to resolve spontaneously. A multiple logistic regression analysis was
      performed by computing the 771 visual observations. The probabilities of success
      of 100-Hz, 5-s tetanus to detect TOF ratios of 0.8, 0.85, and 0.9 were 99%, 96%,
      and 67%, respectively. The sensitivity and specificity of 100-Hz, 5-s tetanus as
      an indicator of TOF ratios of 0.85 and 0.9 are 100% and 75%, 54% and 67%,
      respectively. We conclude that RF100 Hz visual assessment seems to be highly
      sensitive in evaluating residual paralysis, as the absence of RF100 Hz visual
      fading at the AP is compatible with a TOF ratio > 0.85. IMPLICATIONS: After the
      administration of muscle relaxants, the absence of visual fading at the adductor
      pollicis, elicited in anesthetized patients by 100-Hz, 5-s tetanus, is compatible
      with a train-of four ratio > 0.85. Therefore, clinical observation of fading
      after 100-Hz, 5-s tetanus seems to be a highly sensitive test in evaluating
      residual paralysis.

PMID- 9661572
TI  - The effect of intravenous and oral fluconazole on the pharmacokinetics and
      pharmacodynamics of intravenous alfentanil.
AB  - The azole antimycotic fluconazole inhibits cytochrome P450 enzymes. We studied
      the possible interaction of alfentanil with oral and i.v. fluconazole in a three
      phase, double-blind, placebo-controlled, randomized, cross-over study at
      intervals of 4 wk. Nine healthy volunteers were given a single oral dose of
      either fluconazole 400 mg or placebo, followed within 60 min by either i.v.
      fluconazole 400 mg in saline or saline only. The dose of 20 micrograms/kg of
      alfentanil was given i.v. 1 h after the fluconazole/placebo. Venous plasma
      samples were collected, and pharmacodynamic measurements were performed for 10 h.
      Alfentanil clearance was decreased from 3.1 +/- 1.1 mL.min-1.kg-1 to 1.3 +/- 0.3
      mL.min-1. kg-1 after i.v. fluconazole and to 1.4 +/- 0.4 mL.min-1. kg-1 after
      oral fluconazole (P < 0.001). The mean elimination half-life of alfentanil was
      almost doubled after both oral and i.v. fluconazole (P < 0.001). Fluconazole
      increased the subjective effects of alfentanil as quantified on visual analog
      scales (P < 0.01). Correspondingly, both i.v. and oral fluconazole also increased
      the alfentanil-induced respiratory depression by decreasing the respiratory rate
      by 10%-15% (P < 0.05). We conclude that metabolism of alfentanil is inhibited by
      oral and i.v. fluconazole and that caution should be exercised when alfentanil is
      given to patients receiving fluconazole. IMPLICATIONS: We studied the interaction
      of cytochrome P450 3A4 enzyme inhibitor fluconazole with alfentanil. Nine
      volunteers were given placebo or fluconazole 400 mg orally or i.v. Alfentanil 20
      micrograms/kg was given i.v. 1 h after pretreatment. Fluconazole decreased the
      clearance of alfentanil by 55% and increased the alfentanil-induced subjective
      effects.

PMID- 9661573
TI  - Propofol clearance and distribution volume increase in patients with
      hyperthyroidism.
AB  - We investigated propofol pharmacokinetics in seven hyperthyroid (Group H) and
      eight euthyroid (Group E) patients undergoing elective subtotal thyroidectomy.
      Anesthesia was induced with an i.v. injection of 2 mg/kg propofol and maintained
      with a continuous propofol infusion while ventilation was controlled with 60%
      nitrous oxide in oxygen. The propofol infusion rate was adjusted in the range of
      4-10 mg.kg-1.h-1 based on physiological signs such as heart rate and blood
      pressure. Arterial blood was sampled to measure the propofol concentration. The
      mean propofol infusion rates were higher in hyperthyroid than in patients with
      euthyroidism (median values Group H 10.0 mg.kg-1.h-1, Group E 6.5 mg.kg-1.h-1; P
      < 0.05), although the reverse was true for average propofol concentrations (Group
      H 1.8 micrograms/mL, Group E 3.3 micrograms/mL; P < 0.05). Group H also had
      higher values for propofol clearance (5.1 L/min versus 2.5 L/min; P < 0.05) and
      distribution volume at steady state (10.0 L/kg versus 2.8 L/kg; P < 0.05).
      Because distribution volume and clearance in patients with hyperthyroidism were
      increased, propofol concentrations could not reach anesthetic levels.
      IMPLICATIONS: Propofol decreases heart rate and blood pressure, which are
      desirable properties for anesthesia in patients with hyperthyroidism. However,
      because clearance and distribution volume of propofol are increased, propofol
      infusion rates had to be increased to reach anesthetic blood concentrations.

PMID- 9661574
TI  - Desflurane and the nonimmobilizer 1,2-dichlorohexafluorocyclobutane suppress
      learning by a mechanism independent of the level of unconditioned stimulation.
AB  - We previously demonstrated that anesthetics and non-immobilizers suppress
      learning and memory in rats. In the training portion of the test, rats received a
      light plus a footshock and learned to associate the two, as evidenced by
      subsequent potentiation of the response (jumping) to light plus a noise (fear
      potentiated startle). However, anesthetics and nonimmobilizers also decreased the
      response of animals receiving footshocks during training, which suggests that the
      reduction in fear-potentiated startle might reflect analgesia, rather than an
      impairment of learning and memory. Furthermore, although we previously
      demonstrated that the nonimmobilizer 2,3-dichlorohexafluorocyclobutane (2N) could
      completely abolish learning, we did not demonstrate the minimal dose required. In
      the present study, we eliminated analgesia as a confounding factor by training
      rats breathing desflurane and 2N with footshock intensities that produced
      responses at least equal to those produced in control animals. Both desflurane
      and 2N suppressed learning at 0.2 times the minimum alveolar anesthetic
      concentration (MAC) or the MAC predicted from lipid solubility, despite the
      increased footshock intensity. This partial pressure of desflurane equals that
      previously shown to suppress learning at lower footshock intensities. We conclude
      that suppression of learning and memory by desflurane and 2N does not result from
      decreased sensitivity to the unconditioned stimulus (the footshock) and that the
      potency of 2N is consistent with its lipophilicity. IMPLICATIONS: General
      anesthesia eliminates recall of intraoperative events, including pain. Using an
      animal model, we refuted the hypothesis that lack of recall results from the
      analgesia (i.e., the reduced response to painful stimuli produced by inhaled
      drugs) rather than from a direct effect on learning.

PMID- 9661575
TI  - Magnesium sulfate reduces intra- and postoperative analgesic requirements.
AB  - In a randomized, double-blind study with two parallel groups, we assessed the
      analgesic effect of perioperative magnesium sulfate administration in 46 ASA
      physical status I or II patients undergoing arthroscopic knee surgery with total
      i.v. anesthesia. The patients received either magnesium sulfate 50 mg/kg
      preoperatively and 8 mg.kg-1.h-1 intraoperatively or the same volume of isotonic
      sodium chloride solution i.v. Anesthesia was performed with propofol (2 mg/kg for
      induction, 6-8 mg.kg-1.h-1 for maintenance), fentanyl (3 micrograms/kg for
      induction), and vecuronium (0.1 mg/kg for intubation). Intraoperative pain was
      defined as an increase of mean arterial blood pressure and heart rate of more
      than 20% from baseline values after the induction of anesthesia and was treated
      with bolus fentanyl (1-2 micrograms/kg). Postoperative analgesia was achieved
      with fentanyl (0.5 microgram/kg) and evaluated using the pain visual analog scale
      for 4 h. During the intraoperative and postoperative periods, patients in the
      magnesium group required significantly less fentanyl than those in the control
      group (control group 0.089 +/- 0.02 microgram.kg-1.min-1 versus magnesium group
      0.058 +/- 0.01 microgram.kg-1.min-1; P < 0.05 and control group 0.021 +/- 0.013
      microgram.kg-1.min-1 and magnesium group 0.0031 +/- 0.0018 microgram.kg-1.min-1;
      P < 0.01 for intraoperative and postoperative periods, respectively). We conclude
      that, in a clinical setting with almost identical levels of surgical stimulation,
      i.v. magnesium sulfate administration reduces intraoperative and postoperative
      analgesic requirements compared with isotonic sodium chloride solution
      administration. IMPLICATIONS: The perioperative administration of i.v. magnesium
      sulfate reduces intra- and postoperative analgesic requirements in patients with
      almost identical levels of surgical stimulus. Our results demonstrate that
      magnesium can be an adjuvant to perioperative analgesic management.

PMID- 9661577
TI  - Atrial fibrillation and thromboembolism.

PMID- 9661576
TI  - Synergism between sevoflurane and intravenous fentanyl on A delta and C
      somatosympathetic reflexes in dogs.
AB  - In this study, we defined the nature of the interactions between sevoflurane and
      fentanyl on spontaneous and reflex-evoked sympathetic activity, resting heart
      rate (HR), and mean arterial pressure (MAP). Spontaneous renal sympathetic nerve
      activity (RSNA) and A delta- and C-fiber-mediated somatosympathetic reflexes,
      evoked by electrical stimulation of radial nerves, and HR and MAP were recorded
      in anesthetized dogs. In one group, the effects of incremental doses of 2-64
      micrograms/kg fentanyl i.v. were observed. It had a greater inhibitory effect on
      C than on A delta reflexes, which were abolished by mean cumulative doses of 64
      micrograms/kg and approximately 128 micrograms/kg, respectively. Although 1.5%
      sevoflurane reduced C reflexes by 28% and A delta reflexes by only 12%, it
      reduced the total doses of fentanyl required for their abolition to 32
      micrograms/kg and 64 micrograms/kg, respectively. Mean RSNA, HR, and MAP values
      were reduced by 46%, 54%, and 30%, respectively, by fentanyl alone and by 23%,
      11%, and 17%, respectively, in response to 1.5% sevoflurane. The combination of
      fentanyl and sevoflurane caused reductions of 44%, 54%, and 41%, respectively,
      which indicates a less than additive effect. These results indicate that
      sevoflurane interacts synergistically with fentanyl to depress A delta and C
      somatosympathetic reflexes, whereas for RSNA, HR, and MAP, their effects were
      less than the additive. IMPLICATIONS: Although fentanyl caused a greater
      depression of C than of A delta reflexes to the point of abolition, the maximal
      depression of spontaneous sympathetic activity, heart rate, and arterial pressure
      occurred at smaller doses. The combined depressant effects of sevoflurane and
      fentanyl were synergistic on somatosympathetic reflexes but were less than
      additive on spontaneous sympathetic activity, heart rate, and arterial pressure.

PMID- 9661578
TI  - Akathisia and anesthesia: refusal of surgery after the administration of
      metoclopramide.

PMID- 9661579
TI  - Esophageal rupture associated with the use of the Combitube.

PMID- 9661580
TI  - A new continuous catheter delivery system.

PMID- 9661581
TI  - Succinylcholine cannot relieve an airway obstruction caused by pharyngeal and
      laryngeal edema.

PMID- 9661582
TI  - No evidence of sevoflurane-induced renal injury in volunteers.

PMID- 9661583
TI  - Ohmeda 7900 Ventilator Flow Sensor failure.

PMID- 9661584
TI  - Epidural saline and combined epidural-spinal anesthesia.

PMID- 9661585
TI  - Intrapulmonary shunt fraction and prostaglandin E1.

PMID- 9661586
TI  - Acute normovolemic hemodilution versus predonation: what is the actual cost?

PMID- 9661587
TI  - Clinical review 97: Potential health benefits of dietary phytoestrogens: a review
      of the clinical, epidemiological, and mechanistic evidence.
AB  - Phytoestrogens represent a family of plant compounds that have been shown to have
      both estrogenic and antiestrogenic properties. A variety of these plant compounds
      and their mammalian metabolic products have been identified in various human body
      fluids and fall under two main categories: isoflavones and lignans. A wide range
      of commonly consumed foods contain appreciable amounts of these different
      phytoestrogens. For example, soy and flax products are particularly good sources
      of isoflavones and lignans, respectively. Accumulating evidence from molecular
      and cellular biology experiments, animal studies, and, to a limited extent, human
      clinical trials suggests that phytoestrogens may potentially confer health
      benefits related to cardiovascular diseases, cancer, osteoporosis, and menopausal
      symptoms. These potential health benefits are consistent with the epidemiological
      evidence that rates of heart disease, various cancers, osteoporotic fractures,
      and menopausal symptoms are more favorable among populations that consume plant
      based diets, particularly among cultures with diets that are traditionally high
      in soy products. The evidence reviewed here will facilitate the identification of
      what is known in this area, the gaps that exist, and the future research that
      holds the most potential and promise.

PMID- 9661588
TI  - New perspectives on the skeletal role of estrogen.

PMID- 9661589
TI  - Associations between low levels of serum estradiol, bone density, and fractures
      among elderly women: the study of osteoporotic fractures.
AB  - To evaluate the skeletal effects of endogenous serum estradiol, we measured bone
      mineral density (BMD) at the calcaneus and radius (single photon absorptiometry)
      and at the hip and spine (dual x-ray absorptiometry) in 274 women aged 65 yr or
      more who participated in the Study of Osteoporotic Fractures. Lateral radiographs
      of the thoracic and lumbar spine were also taken, and serum was assayed for
      estradiol. Those who had estradiol levels from 10-25 pg/mL had 4.9%, 9.6%, 7.3%,
      and 6.8% greater BMD at total hip, calcaneus, proximal radius, and spine than
      those with levels below 5 pg/mL. After multiple adjustments, BMD differences
      remained statistically significant and corresponded to about 0.4 SD. Vertebral
      deformities were less prevalent among women whose estradiol level exceeded 5
      pg/mL; the multiple adjusted odds ratio was 0.4 (95% confidence interval, 0.2
      0.8). We conclude that physiologically low estradiol has a salutary effect on the
      skeleton in elderly women, possibly by reducing skeletal remodeling.

PMID- 9661591
TI  - Vitamin D receptor (VDR) and parathyroid hormone messenger ribonucleic acid
      levels correspond to polymorphic VDR alleles in human parathyroid tumors.
AB  - Calcitriol, via its receptor (VDR) is a main regulator of PTH secretion and
      parathyroid cell proliferation. Recently, marked overrepresentation of the
      polymorphic VDR alleles b, a, and T was found in patients with primary
      hyperparathyroidism (pHPT), which suggests pathogenic importance in the disease.
      Using the ribonuclease protection assay, relative VDR and PTH messenger
      ribonucleic acid (mRNA) levels of parathyroid adenomas from 42 patients with
      sporadic pHPT were related to these VDR polymorphisms. The tumors of patients
      homozygous for the b, a, or T alleles demonstrated significantly lower VDR and
      higher PTH mRNA levels than those exhibiting the BB, AA, or tt genotypes (P <
      0.0001-0.02), whereas heterozygotes had intermediate values. A similar
      discrepancy was found when comparing the baT and non-baT haplotypes (0.042 +/-
      0.005 vs. 0.064 +/- 0.004 for VDR; 34.4 +/- 3.7 vs. 21.6 +/- 2.2 for PTH; both P
      < 0.005). The lower VDR mRNA levels associated with the b, a, and T alleles may
      affect the calcitriol-mediated control of parathyroid function and thereby
      contribute to the development of sporadic pHPT.

PMID- 9661590
TI  - Examination of genotype and phenotype relationships in 14 patients with apparent
      mineralocorticoid excess.
AB  - Apparent mineralocorticoid excess (AME) is a genetic disorder causing pre- and
      postnatal growth failure, juvenile hypertension, hypokalemic metabolic alkalosis,
      and hyporeninemic hypoaldosteronism due to a deficiency of 11 beta-hydroxysteroid
      dehydrogenase type 2 enzyme activity (11 beta HSD2). The 11 beta HSD2 enzyme is
      responsible for the conversion of cortisol to the inactive metabolite cortisone
      and therefore protects the mineralocorticoid receptors from cortisol
      intoxication. Several homozygous mutations are associated with this potentially
      fatal disease. We have examined the phenotype, biochemical features, and genotype
      of 14 patients with AME. All of the patients had characteristic signs of a severe
      11 beta HSD2 defect. Birth weights were significantly lower than those of their
      unaffected sibs. The patients were short, underweight, and hypertensive for age.
      Variable damage of one or more organs (kidneys, retina, heart, and central
      nervous system) was found in all of the patients except one. The follow-up
      studies of end-organ damage after 2-13 yr of treatment in six patients
      demonstrated significant improvement in all patients. The urinary metabolites of
      cortisol demonstrated an abnormal ratio with predominance of cortisol
      metabolites, i.e. tetrahydrocortisol plus 5 alpha
      tetrahydrocortisol/tetrahydrocortisone was 6.7-33, whereas the normal ratio is
      1.0. Infusion of [11-3H]cortisol resulted in little release of tritiated water,
      indicating the failure of the conversion of cortisol to cortisone. Thirteen
      mutations in the HSD11B2 gene have been previously published, and we report three
      new genetic mutations in two patients, one of whom was previously unreported. All
      of the patients had homozygous defects except one, who was a compound
      heterozygote. Our first case had one of the most severe mutations, resulting in
      the truncation of the enzyme 11 beta HSD2, and died at the age of 16 yr while
      receiving treatment. Three patients with identical homozygous mutations from
      different families had varying degrees of severity of clinical and biochemical
      features. Due to the small number of patients with identical mutations, it is
      difficult to correlate genotype with phenotype. In some cases, early and vigilant
      treatment of AME patients may prevent or improve the morbidity and mortality of
      end-organ damage such as renal or cardiovascular damage and retinopathy. The
      outcome of treatment in more patients may establish the efficacy of treatment.

PMID- 9661592
TI  - Leptin levels in children with central precocious puberty.
AB  - Several studies have suggested that sufficient serum leptin levels may be
      involved in the initiation of puberty. To assess further the relationship between
      leptin and the onset of puberty in humans, we measured the serum leptin
      concentration in children with central precocious puberty (CPP). We studied 65
      children with either idiopathic (IPP; n = 50 girls and 3 boys) or neurogenic
      central precocious puberty (NPP; n = 5 girls and 7 boys). The serum leptin levels
      in these patients were compared with normative data from healthy children and
      adolescents using SD scores that adjust for body mass index (BMI) and Tanner
      stage. The mean SD scores of IPP and NPP girls were +0.4 +/- 0.1 and +1.0 +/-
      0.5, respectively, compared with that of age-matched prepubertal girls and +0.7
      +/- 0.2 and +1.6 +/- 0.6 compared with that of girls matched for pubertal stage.
      The CPP girls with lower BMIs contributed larger SD scores, such that the leptin
      SD score was negatively correlated with BMI. A similar, modest increase in leptin
      levels in the CPP girls was evident when additional normative data were
      considered. The mean leptin SD scores of IPP and NPP boys were -0.9 +/- 0.5 and
      +0.7 +/- 0.3, respectively, compared with that of normal boys at Tanner stage 3
      4. Serum leptin levels in the boys with CPP were not different from those in
      healthy boys in any of the normative studies. These data should be interpreted
      cautiously, but they suggest that girls with CPP have modestly elevated serum
      leptin concentrations compared with those in healthy children and adolescents. In
      addition, the negative correlation between the leptin SD score and BMI suggests
      that sufficient leptin levels may be associated with initiation of puberty in
      girls.

PMID- 9661593
TI  - Relationship of serum sex steroid levels and bone turnover markers with bone
      mineral density in men and women: a key role for bioavailable estrogen.
AB  - Estrogen (E) deficiency associated with the menopause is the major cause of bone
      loss in aging women. However, men also lose significant amounts of bone with age,
      but they do not have the equivalent of menopause, and serum total testosterone
      (T) and E levels decline only marginally with age in men. Thus, it has been
      difficult to attribute bone loss in aging men to either T or E deficiency. Here,
      we show in a population-based, age-stratified sample of 346 men, aged 23-90 yr,
      that serum total T and E (estradiol plus estrone) levels decreased over the life
      span by 30% and 12%, respectively, but bioavailable (or nonsex hormone-binding
      globulin-bound) T and E levels decreased by 64% and 47%, respectively. In these
      men and in a parallel cohort of 304 women, aged 21-94 yr, serum PTH increased 84%
      and 64% over the life span, and urinary N-telopeptide of type I collagen (NTx)
      excretion, a bone resorption marker, increased 77% and 80% between age 50-85 yr
      in the men and women, respectively. By univariate analyses, serum bioavailable T
      and E levels correlated positively with bone mineral density (BMD) at the total
      body, spine, proximal femur, and distal radius and negatively with urinary NTx
      excretion in men and women. Urinary NTx excretion was also negatively associated
      with BMD in both sexes. By multivariate analyses, however, serum bioavailable E
      level was the consistent independent predictor of BMD in both men and
      postmenopausal women. Thus, bioavailable E levels decline significantly with age
      and are important predictors of BMD in men as well as women. These studies
      suggest that in contrast to traditional belief, age-related bone loss may be the
      result of E deficiency not just in postmenopausal women, but also in men.

PMID- 9661594
TI  - Impairment of bone status in patients with central diabetes insipidus.
AB  - The aim of the current study was to evaluate the biochemical parameters of bone
      metabolism and the bone mineral density (BMD) in patients with central diabetes
      insipidus, either treated or not treated with endonasal desmopressin. Eighteen
      patients with central diabetes insipidus and 18 sex- and age-matched healthy
      subjects entered the study. The patients were divided into 2 groups: patients who
      did not receive treatment with desmopressin for at least 1 yr (group 1), and
      patients chronically treated with desmopressin since the diagnosis of diabetes
      insipidus (group 2). Serum osteocalcin and urinary cross-linked N-telopeptide of
      type I collagen levels were measured in all patients and controls using RIA and
      enzyme-linked immunosorbent assay kits, respectively. BMD was measured at the
      lumbar spine (L1-L4) and at the femoral neck in all subjects, using a Hologic QDR
      1000 analyzer (Hologic Inc., Waltham, MA). Serum osteocalcin concentrations were
      significantly lower, both in patients of group 1 and group 2, compared with
      healthy subjects (5.1 +/- 0.6 and 4.5 +/- 0.3 vs. 7.9 +/- 0.2 micrograms/L, P <
      0.05), whereas urinary cross-linked N-telopeptide of type I collagen
      concentrations were similar in the three groups of subjects (72.8 +/- 2.2, 71.6
      +/- 2.7, and 64.6 +/- 1.7 nmol bone collagen equivalent/mmol creatinine). BMD was
      significantly decreased in patients of groups 1 and 2, compared with controls,
      both at lumbar spine (0.84 +/- 0.06 and 0.87 +/- 0.04 vs. 1.01 +/- 0.02 g/cm2, P
      < 0.05) and femoral neck (0.78 +/- 0.06 and 0.80 +/- 0.04 vs. 0.93 +/- 0.02
      g/cm2, P < 0.05). A significant inverse correlation was found between disease
      duration and BMD values, evaluated as T scores, both at lumbar spine (group 1: r
      = -0.952, P < 0.005; group 2: r = -0.921, P < 0.001) and at femoral neck (group
      1: r = -0.914, P < 0.05; group 2: r = -0.683, P < 0.05). In conclusion, patients
      with central diabetes insipidus had a significant bone impairment, compared with
      healthy subjects. Replacement with endonasal desmopressin at standard doses was
      not able to prevent or reverse the bone impairment. These findings suggest that,
      in patients with central diabetes insipidus, bone status analysis is mandatory;
      and a bone-loss preventing treatment might be beneficial.

PMID- 9661595
TI  - Effects of estrogen or testosterone on self-reported sexual responses and
      behaviors in hypogonadal adolescents.
AB  - The purpose of this study was to investigate the effects of administration of sex
      steroids on self-reported sexual responses and behaviors in hypogonadal
      adolescents. We used a randomized, double blind, placebo-controlled, cross-over,
      clinical trial as the experimental design. The subjects were 39 boys and 16 girls
      with delayed puberty. We treated girls with oral conjugated estrogen and boys
      with testosterone enanthate in 3 dose levels intended to simulate early, middle,
      and late pubertal levels. We administered a modification of the Udry sexual
      behavior questionnaire after each 3-month placebo and treatment period to detect
      the effect of sex steroids on self-reported sexual behaviors and responses. We
      employed a strict intent to treat statistical analytical model. The data showed
      significant effects of the administration of testosterone to boys causing
      increases in nocturnal emission and touching behaviors at the mid- and high
      doses. No other treatment effects on sexual behaviors or responses were seen in
      boys. For girls, there was a significant increase in necking caused by the
      administration of estrogen only at the late pubertal dose. No other treatment
      effects on sexual behaviors or responses were seen in girls. We noted some gender
      differences for thinking about sex, sexual "turn-on," and the nature of sexual
      behavior. The administration of physiological doses of sex steroids to boys or
      girls with delayed puberty have few effects on sexual behaviors and responses.

PMID- 9661596
TI  - Association between serum insulin growth factor-I (IGF-I) and a simple sequence
      repeat in IGF-I gene: implications for genetic studies of bone mineral density.
AB  - We recently demonstrated that insulin growth factor-I (IGF-I) cosegregates with
      bone mineral density (BMD) in progenitor crosses of two inbred strains of mice.
      Additionally, we reported that men with idiopathic osteoporosis (IOM) have low
      serum IGF-I levels, which can be related to BMD and bone turnover. In this study,
      we considered the possibility that serum IGF-I levels are influenced by molecular
      genetic variation in the IGF-I structural gene, and that a polymorphic
      microsatellite (CA repeat) in this locus can be used as a genetic marker for such
      comparisons. We studied 171 men and women, classified according to the trial in
      which they were participating. First, in 25 Caucasian men with IOM we noted a
      very high frequency (64%) of homozygosity for the most common allele (192 bp) in
      a dinucleotide repeat 1 kb upstream from the transcription start site of the IGF
      I gene. This compared with a frequency of only 32% in healthy populations (both
      men and women) (P < 0.004). Next, we determined that for 116 healthy Caucasian
      men and women the 192/192 genotype was associated with lower serum IGF-I levels
      than all other genotypes (192/192: 129 +/- 7 ng/mL vs. others: 154 +/- 7 ng/mL, P
      = 0.03). We also noted that subjects possessing one 194-bp allele exhibited serum
      IGF-I levels 25% higher than those homozygous for 192 bp (192/192), (P < 0.005)
      even after correction for age and sex. Similarly, for men with the 192/192
      genotype, serum IGF-I concentrations were lower than any other genotype (145 +/-
      10 ng/mL vs. 183 +/- 9 ng/ml P < 0.02). In conclusion, low serum IGF-I levels
      found in men with IOM are associated with homozygosity for a specific allele of
      the IGF-I microsatellite (192/192), and individual variation in serum IGF-I
      levels is influenced by genetic factors and may be specifically influenced by
      variation at the IGF-I structural locus. Further family and pedigree studies are
      needed to characterize the relationship of bone mass acquisition to the IGF-I
      genotype.

PMID- 9661597
TI  - Improved diagnostic accuracy of inferior petrosal sinus sampling over imaging for
      localizing pituitary pathology in patients with Cushing's disease.
AB  - The majority of patients with Cushing's disease can be cured by transsphenoidal
      microsurgery; however, precise localization of the pituitary source of ACTH is
      not always possible by standard imaging techniques. Bilateral venous sampling
      from the inferior petrosal sinuses (IPSS) is also useful for diagnosing Cushing's
      disease, but the interpretation of discordant findings between IPSS and imaging
      remains problematic. We tested the ability of imaging and IPSS to localize an
      ACTH-secreting pituitary lesion in comparison to definitive histopathological
      examination of the pituitary in patients with Cushing's disease (n = 37).
      Bilateral IPS catheterization was technically feasible in 32 patients and
      provided evidence of lateralization in 31 patients. Histological examination
      confirmed a corticotropic adenoma in 28 patients and corticotropic hyperplasia in
      2 patients; Crooke's hyaline change was found in 7 patients, among whom 1
      subsequently was found to have an ectopic sphenoid corticotropic adenoma, and the
      remainder had suspected microadenomas that were not identified microscopically.
      Accurate localization of the pituitary lesion was more frequent when based on
      IPSS results than on imaging studies (70% vs. 49%, P < 0.06). The 2 tests
      provided directly discrepant results for 8 patients; among these, IPSS was more
      likely than imaging to agree with final pathology (63% vs. 13%, P < 0.10).
      Imaging was entirely normal for another 9 patients, in whom IPSS accurately
      localized the lesion for the majority (89%; 95% confidence interval: 50-99%). We
      suggest that IPSS is an effective tool for localizing pituitary pathology and
      planning surgery for patients with Cushing's disease.

PMID- 9661598
TI  - Filter paper blood spot assay of human insulin-like growth factor I (IGF-I) and
      IGF-binding protein-3 and preliminary application in the evaluation of growth
      hormone status.
AB  - To facilitate broader applications of insulin-like growth factor I (IGF-I) and
      IGF-binding protein-3 (IGFBP-3) analysis, we developed procedures for their
      measurements in extracts of whole blood dried on filter paper. A single 8-mm
      diameter filter paper disc containing about 13 microL blood was used. IGFBP-3 was
      efficiently extracted in a buffer within 1 h of incubation. IGF-I extraction
      involved incubation in buffer followed by acidification and neutralization steps.
      Blood spot assays showed intra- and interassay coefficients of variation
      (including interspot variations) of 5.4-16.7% for IGF-I and 6.6-11.7% for IGFBP
      3; recoveries were 97 +/- 7.1% and 101 +/- 8.7%, respectively. Recoveries of IGF
      I and IGFBP-3 in response to 4- to 8-fold variations in extraction buffer volume
      were 97 +/- 8.2% and 107 +/- 6.1%, respectively. Dried blood spot IGF-I and IGFBP
      3 showed greater than 1-month stability at -20 C, 4 C, and room temperature and
      retained more than 65% of the immunoreactivity after approximately 1 month at 37
      C. Both IGF-I and IGFBP-3 were contained within the plasma fraction of whole
      blood, and variations (mean +/- SD) in IGF-I (204 +/- 29 micrograms/L) and IGFBP
      3 (4.4 +/- 0.48 mg/L) measured in extracts of dried blood spot with adjusted
      hematocrit of 0.2-0.62 were acceptable. IGF-I and IGFBP-3 in paired plasma and
      dried blood spot extracts of random samples (n = 46) showed excellent correlation
      (r > 0.94) with slopes of near unity. Compared to conventional methods, the
      filter paper procedures were equally effective in distinguishing IGF-I and IGFBP
      3 levels in untreated GH receptor-deficient (n = 11) and age-matched normal
      controls (n = 16). We conclude that blood collected on filter paper is ideal for
      IGF-I and IGFBP-3 analysis and may find applications in pediatric and large scale
      infant screening programs.

PMID- 9661599
TI  - Thyrotropin receptor epitopes recognized by graves' autoantibodies developing
      under immunosuppressive therapy.
AB  - Abnormal modulation of the immune system is a prerequisite for the expression of
      Graves' disease. Thus, when hyperthyroidism developed in a renal transplant
      recipient under long term immunosuppression with cyclosporine A and prednisone,
      we carefully evaluated the basis for her hyperthyroidism and her state of
      immunosuppression. Immunosuppression was confirmed by finding markedly deficient
      lymphocyte responses to common mitogens. Lymphocyte phenotype frequencies were
      those previously found in Graves', i.e. elevated frequencies of CD3/DR, CD5/26,
      and CD3/25 lymphocytes. There was also reversal of the CD4/CD8 ratio due to
      increased CD8 frequency; this is not a typical finding in autoimmune
      hyperthyroidism, but has been seen in the intrathyroidal lymphocyte populations
      of some Graves' patients and is associated with other forms of autoimmunity. The
      patient's serum contained a broad spectrum of TSH receptor autoantibodies
      (TSHRAbs) characteristic of Graves' disease. To determine whether these were an
      unusual population of autoantibodies, we determined their functional epitopes
      before and for nearly 1 yr after radioiodine therapy. Stimulating TSHRAbs that
      increase cAMP levels were human receptor (TSHR) specific and consistently
      recognized functional epitopes located on TSHR residues 90-165. Stimulating
      TSHRAbs that increased arachidonate release and inositol phosphate levels
      recognized residues 25-90, as did TSH binding inhibitory Igs present in the
      patient. These data demonstrate that Graves' disease with a wide array of TSHRAbs
      can develop in a patient despite adequate immunosuppression. More importantly,
      they show that the cAMP-stimulating TSHRAb associated with disease expression in
      this patient had a homogeneous subtype dependent on TSHR residues 90-165. As
      persistence of this type of TSHRAb over time has been associated with resistance
      to methimazole therapy in Graves' patients, we speculate that the development and
      persistence of TSHRAb with this homogeneous epitope may be linked to resistance
      to immunosuppressive therapy.

PMID- 9661600
TI  - Decreased leptin levels in normal weight women with hypothalamic amenorrhea: the
      effects of body composition and nutritional intake.
AB  - Leptin is a protein encoded by the ob gene and expressed in adipocytes. A
      sensitive marker of nutritional status, leptin is known to correlate with fat
      mass and to respond to changes in caloric intake. Leptin may also be an important
      mediator of reproductive function, as suggested by the effects of leptin
      infusions to restore ovulatory function in an animal model of starvation. We
      hypothesized that leptin levels are decreased in women with hypothalamic
      amenorrhea and that leptin may be a sensitive marker of overall nutritional
      status in this population. We, therefore, measured leptin levels and caloric
      intake in 21 women with hypothalamic amenorrhea (HA) and 30 age-, weight-, and
      body fat-matched eumenorrheic controls. Age (24 +/- 5 vs. 24 +/- 3 yr), body mass
      index (20.6 +/- 1.3 vs. 21.1 +/- 1.5 kg/m2), percent ideal body weight (94.9 +/-
      5% vs. 96.3 +/- 6.3%), and fat mass (14.2 +/- 3.6 vs. 15.5 +/- 2.9 kg, determined
      by dual energy x-ray absortiometry) did not differ between the groups. Leptin
      levels were significantly lower in the HA subjects compared with those in the
      controls (7.1 +/- 3.0 vs. 10.6 +/- 4.9 micrograms/L; P = 0.005). Total caloric
      intake (1768 +/- 335 vs. 2215 +/- 571 cal/day; P = 0.003), fat intake (333 +/-
      144 vs. 639 +/- 261 cal/day; P < 0.0001), and insulin levels (5.6 +/- 1.2 vs. 7.4
      +/- 3.2 microU/mL; P = 0.015) were lower in the women with HA than in the
      eumenorrheic controls. The difference in leptin levels remained significant after
      controlling for insulin (P = 0.023). These data are the first to demonstrate
      hypoleptinemia, independent of fat mass, in women with HA. The hypoleptinemia may
      reflect inadequate calorie intake, fat intake, and/or other subclinical
      nutritional disturbances in women with HA. The mechanism and reproductive
      consequences of low leptin in this large population of women remain unknown.

PMID- 9661601
TI  - A novel, nongenomic action of estrogen on the cardiovascular system.
AB  - To examine the time course and mechanisms of action of single doses of estrogen
      on the skin microvasculature, two double-blind placebo-controlled cross-over
      studies were conducted in healthy young men using the noninvasive technique of
      laser Doppler velocimetry with iontophoretic application of vasodilator
      substances. Estradiol (2 mg sublingually) produced a significant increase in the
      response to the endothelial vasodilator acetylcholine (ACh) after 15 min, but not
      after 20 or 30 min. The mean plasma estradiol concentration increased from 89.4
      +/- 9 pmol/L at baseline to 486.6 +/- 218 pmol/L at 15 min. An i.v. bolus of 25
      mg conjugated equine estrogens produced significant increases in the responses to
      ACh at 15 and 20 min but not at 30 min. There was no change in responses to the
      nonendothelial vasodilators sodium nitroprusside or nicotine, and administration
      of placebo produced no change in ACh responses at any time point. These
      experiments show that, at plasma estradiol concentrations within the
      physiological range for premenopausal women, estrogens act directly on the
      cutaneous microvasculature through a rapid onset, rapid offset, nongenomic
      mechanism that is specific to the endothelium; in addition, it supports the view
      that estrogens can act on the male cardiovascular system in a manner that is
      potentially clinically beneficial.

PMID- 9661602
TI  - Adrenal androgen excess in the polycystic ovary syndrome: sensitivity and
      responsivity of the hypothalamic-pituitary-adrenal axis.
AB  - Over 50% of patients with the polycystic ovary syndrome (PCOS) demonstrate excess
      levels of adrenal androgens (AAs), particularly dehydroepiandrosterone sulfate
      (DHS). Nonetheless, the mechanism for the AA excess remains unclear. It has been
      noted that in PCOS the pituitary and ovarian responses to their respective
      trophic factors (i.e. GnRH and LH, respectively) are exaggerated. Similarly, we
      have postulated that excess AAs in PCOS arises from dysfunction of the
      hypothalamic-pituitary-adrenal axis, due to 1) exaggerated pituitary secretion of
      ACTH in response to hypothalamic CRH, 2) excess sensitivity/responsivity of AAs
      to ACTH stimulation, or 3) both. To test this hypothesis we studied 12 PCOS
      patients with AA excess (HI-DHS; DHS, > 8.1 mumol/L or 3000 ng/mL), 12 PCOS
      patients without AA excess (LO-DHS; DHS, < 7.5 mumol/L or 2750 ng/mL), and 11
      controls (normal subjects). Each subject underwent an acute 90-min ovine CRH
      stimulation test (1 microgram/kg) and an 8-h incremental i.v. stimulation with
      ACTH-(1-24) at doses ranging from 20-2880 ng/1.5 m2.h) with a final bolus of 0.25
      mg. All patient groups had similar mean body mass indexes and ages, and both
      tests were performed in the morning during the follicular phase (days 3-10) of
      the same menstrual cycle, separated by 48-96 h. During the acute ovine CRH
      stimulation test, no significant differences in the net maximal response (i.e.
      change from baseline to peak level) for ACTH, dehydroepiandrosterone (DHA),
      androstenedione (A4), or cortisol (F) or for the DHA/ACTH, A4/ACTH, or F/ACTH
      ratios was observed. Nonetheless, the net response of DHA/F and the areas under
      the curve (AUCs) for DHA and DHA/F indicated a greater response for HI-DHS vs. LO
      DHS or normal subjects. The AUC for A4 and A4/F and the delta A4/delta F ratio
      (delta = net maximum change) indicated that HI-DHS and LO-DHS had similar
      responses, which were greater than that of the normal subjects, although the
      difference between LO-DHS patients and normal subjects reached significance only
      for the AUC of the A4 response. No difference in the sensitivity (i.e. threshold
      or minimal stimulatory dose) to ACTH was noted between the groups for any of the
      steroids measured. Nonetheless, the average dose of ACTH-(1-24) required for a
      threshold response was higher for DHA than for F and A4 in all groups. No
      difference in mean responsivity (slope of response to incremental ACTH
      stimulation) was observed for DHA and F between study groups, whereas the
      responsivity of A4 was higher in HI-DHS patients than in normal or LO-DHS women.
      The net maximal and the overall (i.e. AUC) responses of DHA were greater for HI
      DHS than for normal or LO-DHS women. The response of A4 and the delta A4/delta F
      ratio were greater for HI-DHS patients than for LO-DHS patients or normal
      subjects. Alternatively, HI-DHS and LO-DHS patients had similar overall responses
      (i.e. AUC) for A4 or A4/F, although both were greater than those of normal
      subjects. The relative differences in response to incremental ACTH stimulation
      between steroids was consistent for all subject groups studied, i.e. A4 > F or
      DHA. In conclusion, our data suggest that AA excess in PCOS patients is related
      to an exaggerated secretory response of the adrenal cortex for DHA and A4, but
      not to an altered pituitary responsivity to CRH or to increased sensitivity of
      these AAs to ACTH stimulation. Whether the increased responsivity to ACTH for
      these steroids is secondary to increased zonae reticularis mass or to differences
      in P450c17 alpha activity, particularly of the delta 4 pathway, remains to be
      determined.

PMID- 9661603
TI  - Randomized trial of pamidronate in patients with thyroid cancer: bone density is
      not reduced by suppressive doses of thyroxine, but is increased by cyclic
      intravenous pamidronate.
AB  - Patients taking suppressive doses of T4 are thought to have accelerated bone loss
      and increased risk of osteoporosis. We therefore randomize 55 patients taking
      suppressive doses of T4 to treatment with pamidronate (APD) 30 mg i.v. every 3
      months for 2 yr (APD/T4), or placebo (placebo/T4). Patients had measurements of
      bone mineral density (BMD) of the spine, hip, radius, and total body every 6
      months for 2 yr. There was no significant bone loss at any site in the placebo/T4
      group. Ninety five percent confidence intervals excluded a rate of bone loss >
      0.89%/yr for the spine and > 0.31%/yr at the total hip. When men were excluded
      from the analysis, there still was no significant bone loss for the placebo/T4
      group, and confidence intervals did not change. The APD/T4 group showed increases
      in spine (4.3%, P = 0.0001), total hip (1.4%, P < 0.05), and trochanteric (3.0%,
      P = 0.0001) BMDs. In conclusion, premenopausal women and men on suppressive
      therapy with T4 do not lose bone rapidly, and are not at increased risk of
      developing osteoporosis. A regimen of 30 mg APD given every 3 months for 2 yr
      causes significant suppression of bone resorption and increases in BMD, and may
      be an acceptable alternative treatment for osteoporosis in patients who cannot
      tolerate oral bisphosphonates.

PMID- 9661604
TI  - Concentration of insulin-like growth factor (IGF)-I and -II in iliac crest bone
      matrix from pre- and postmenopausal women: relationship to age, menopause, bone
      turnover, bone volume, and circulating IGFs.
AB  - Insulin-like growth factor-I (IGF-I) and -II are important local regulators of
      bone metabolism, but their role as determinants of human bone mass is still
      unclear. In the present study, we analyzed the concentration of IGF-I and -II in
      the bone matrix of 533 human biopsies from the iliac crest that were obtained
      during surgery for early breast cancer. There was an inverse association of bone
      matrix IGF-I concentration with age that was unaffected by menopause. Bone matrix
      IGF-I was positively associated with histomorphometric and biochemical parameters
      of bone formation and bone resorption and with cancellous bone volume. Based on
      the estimates of the linear regression analysis, women with a bone matrix IGF-I
      concentration 2 SD above the mean had a 20% higher bone volume than women with a
      bone matrix IGF-I concentration 2 SD below the mean. In contrast, serum IGF-I was
      neither correlated with bone turnover nor with bone volume and was only weakly
      associated with bone matrix IGF-I when adjusted for the serum concentration of
      IGF binding protein-3. Bone matrix IGF-II was positively associated with the
      osteoblast surface, but in contrast to IGF-I, tended to be positively associated
      with age and was unrelated to cancellous bone volume. In summary, our study
      suggests the following. 1) The concentration of IGF-I in cancellous bone
      undergoes age-related decreases that are similar to those of circulating IGF-I.
      2) Menopause has no effect on this age-related decline. 3) Physiological
      differences in bone matrix IGF-I are associated with differences in iliac crest
      cancellous bone volume. 4) Bone matrix IGF-I is a better predictor of cancellous
      bone volume than circulating IGF-I. 5) The role of IGF-II in human bone tissue is
      clearly distinct from that of IGF-I.

PMID- 9661605
TI  - Free fatty acids and insulin resistance during pregnancy.
AB  - The purpose of this study was to determine whether elevation of plasma free fatty
      acids (FFA) in early pregnancy would cause alterations in insulin-stimulated
      glucose disposal similar to those occurring in late gestation. Seven glucose
      tolerant women underwent 4-h euglycemic hyperinsulinemic (1 mU/kg.min) clamping
      during the early second trimester of pregnancy (14-17 weeks) on 2 consecutive
      days, receiving either lipid (Liposyn II; 1.5 mL/min) and heparin (0.4 U/kg.min;
      L/H) or saline/glycerol (2.25 g/h; S/G) infusions. Rates of total body glucose
      disposal (6,6-2H2 glucose) and of carbohydrate and fat oxidation (indirect
      calorimetry) were determined at hourly intervals. Blood glucose was clamped at
      about 85 mg/dL. Plasma FFA increased from 290 +/- 50 to 1000 +/- 139 mumol/L
      during L/H infusion and decreased from 351 +/- 60 to 35 +/- 11 mumol/L during S/G
      infusion. L/H infusion inhibited insulin stimulation of total body glucose
      disposal by 28% compared with S/G infusion (from 6.7 +/- 0.7 to 4.9 +/- 0.6
      mg/kg.min; P < 0.01). L/H infusion increased fat oxidation from 0.73 +/- 0.04 to
      1.26 +/- 0.2 mg/kg.min (P < 0.05) and decreased carbohydrate oxidation from 2.0
      +/- 0.2 to 1.6 +/- 0.2 mg/kg.min (P < 0.05). Endogenous glucose production
      decreased equally by approximately 70% during L/H and S/G infusions. These data
      showed that elevating plasma FFA levels during early pregnancy inhibits total
      body glucose uptake and oxidation. We conclude that elevation of plasma FFA can
      contribute to the peripheral insulin resistance commonly observed during late
      pregnancy.

PMID- 9661606
TI  - Use of a gonadotropin-releasing hormone antagonist as a physiologic probe in
      polycystic ovary syndrome: assessment of neuroendocrine and androgen dynamics.
AB  - The majority of patients with polycystic ovary syndrome (PCOS) exhibit an
      increase in both the frequency and amplitude of LH secretion, which is thought to
      contribute to the hyperandrogenism associated with this disorder. The increase in
      LH pulse amplitude may reflect either enhanced pituitary sensitivity to GnRH
      and/or an increase in hypothalamic GnRH secretion. To determine whether
      endogenous GnRH secretion is increased in PCOS and to document the degree and
      time course of androgen suppression after acute LH inhibition, the Nal-Glu GnRH
      antagonist was administered s.c. at 4 doses (5, 15, 50, and 150 micrograms/kg) to
      11 women with PCOS. The response to GnRH receptor blockade was compared with data
      from regularly cycling women (n = 50) studied in the early and late follicular,
      and early luteal phases. The response to more prolonged GnRH receptor blockade
      was determined in a subset of patients, in whom 150 micrograms/kg of the GnRH
      antagonist was administered s.c. every 24 h for 3 days (n = 7) and continued for
      7 days in 3 subjects. LH levels decreased in a dose-dependent fashion after
      administration of the GnRH antagonist (P < 0.0001), with a maximum percent
      inhibition of 83 +/- 2%. At all except the 5 micrograms/kg dose, mean LH levels
      remained significantly lower than baseline for up to 20 h post antagonist (P <
      0.002). At all antagonist doses, both the degree and duration of LH suppression
      were similar in PCOS and normal women. The maximum percent inhibition of FSH was
      39 +/- 2%, which was significantly less than that of LH (P < 0.001). Testosterone
      (T) levels fell significantly within 4 h of antagonist administration, with
      maximum percent inhibition of 39 +/- 3% occurring at 8 h. In the patients in whom
      150 micrograms/kg of the antagonist was given for 3-7 days, no further
      suppression of either gonadotropins or T was noted. Our conclusions were: 1) The
      equivalent susceptibility of LH to submaximal GnRH receptor blockade in normal
      and PCOS women suggests that the elevated LH levels in PCOS are not the result of
      an increase in the quantity of GnRH secreted. These data imply that it is the
      frequency of GnRH stimulation per se and/or enhanced pituitary sensitivity to
      endogenous GnRH that underlie the gonadotropin abnormalities in PCOS; and 2) The
      rapid suppression of T with increasing GnRH antagonist dose is consistent with
      acute regulation of T secretion by LH.

PMID- 9661607
TI  - Evaluation of the integrity of the hypothalamic-pituitary-adrenal axis by insulin
      hypoglycemia test.
AB  - We retrospectively reviewed dynamic ACTH and cortisol responses to insulin
      hypoglycemia in 193 subjects with suspected ACTH deficiency to ascertain the
      predictive values of various diagnostic criteria. Based on the achievement of a
      peak cortisol level of 18 micrograms/dL or above, 133 subjects were classified as
      having an intact hypothalamic-pituitary-adrenal (HPA) axis, and 60 subjects were
      determined to have ACTH deficiency. Baseline and peak cortisol concentrations
      were strongly correlated (r = 0.63; P < 0.0001). Peak cortisol increased in
      parallel to ACTH increments, but plateaued at approximately 22 micrograms/dL at
      peak ACTH levels above approximately 75 pg/mL (r = 0.61; P < 0.0001). Basal
      cortisol values above 17 micrograms/dL or below 4 micrograms/dL were highly
      predictive of an intact or impaired HPA axis, respectively, but intermediate
      values had only limited sensitivity and specificity. The criteria of HPA axis
      integrity, defined as an increment in plasma cortisol of more than 7
      micrograms/dL above the baseline or as a doubling of the baseline cortisol value,
      were associated with high false positive and false negative rates. We conclude
      that 1) the baseline morning serum cortisol concentration has very limited
      predictive power in differentiating between normal and impaired HPA function; 2)
      the use of criteria based on incremental changes in serum cortisol from baseline
      leads to unacceptably high false positive and false negative rates; and 3)
      insulin hypoglycemia is still the best indicator of the integrity of the response
      of the HPA axis to stress.

PMID- 9661608
TI  - Effects of eight months treatment with graded doses of a growth hormone (GH)
      releasing peptide in GH-deficient children.
AB  - Stimulation of pituitary GH secretion with administered GHRH can be effective
      therapy for those GH deficient (GHD) patients whose disorder results from
      insufficient endogenous GHRH secretion. We have previously shown that most such
      patients also respond acutely to the GH-releasing peptides (GHRP's), which have a
      different mechanism of action from GHRH, with release of GH. In this study we
      tested whether the GH response to a newer GHRP, GHRP-2, would be sustained over
      time. Six prepubertal children with GHD and growth failure received stepwise
      increasing s.c. doses of GHRP-2, at 0.3, 1.0, and 3.0 micrograms/kg/day, in
      successive 2-month treatment periods, with monitoring of overnight 12 h episodic
      GH secretion and toxicity measures at the end of each period. During a fourth 2
      month period, they received 3 micrograms/kg GHRP-2 together with 3 micrograms/kg
      s.c. GHRH. Serum levels of IGF-I and IGFBP-3 were also measured, and stadiometer
      height measurements were recorded. GHRP-2 administration produced a dosewise
      increase in overnight GH secretion. GH profiles showed that the effect of GHRP-2
      injections was relatively brief, with little effect upon GH secretion later in
      the night. Serum levels of IGF-I and of IGFBP-3 did not increase. Growth velocity
      was higher during GHRP-2 treatment than during pretreatment and post-treatment
      evaluations. There were no side effects or toxicities observed. Thus GHRP-2 is
      well tolerated and is able to stimulate GH secretion. Formulations or routes of
      administration that allow for a longer duration of action will likely be needed
      to use GHRP-2 in therapy.

PMID- 9661609
TI  - Predictors of patients remaining anovulatory during clomiphene citrate induction
      of ovulation in normogonadotropic oligoamenorrheic infertility.
AB  - The diagnostic criteria used to identify patients suffering from polycystic ovary
      syndrome remain controversial. The present prospective longitudinal follow-up
      study was designed to identify whether certain criteria assessed during
      standardized initial screening could predict the response to ovulation induction
      with clomiphene citrate (CC) in 201 patients presenting with oligomenorrhea or
      amenorrhea and infertility. Serum FSH levels were within the normal range (1-10
      IU/L), and all patients underwent spontaneous or progestin-induced withdrawal
      bleeding. Initial CC doses were 50 mg daily for 5 days starting on cycle day 3.
      In the case of an absent response, doses were increased to 100 and 150 mg daily
      in subsequent cycles. First ovulation with CC was used as the end point. After a
      complete follow-up (in the case of a nonresponse, at least 3 treatment cycles
      with daily CC doses up to 150 mg), 156 patients (78%) ovulated. The free androgen
      index (FAI = testosterone/sex hormone-binding globulin ratio), body mass index
      (BMI), cycle history (oligomenorrhea vs. amenorrhea), serum androgen
      (testosterone and/or androstenedione) levels, and mean ovarian volume assessed by
      transvaginal sonography were all significantly different (P < 0.01) in responders
      from those in nonresponders. FAI was chosen to be the best predictor in
      univariate analysis. The area under the receiver operating characteristics curve
      in a multivariate prediction model including FAI, BMI, cycle history, and mean
      ovarian volume was 0.82. Patients whose ovaries are less likely to respond to
      stimulation by FSH due to CC treatment can be predicted on the basis of initial
      screening characteristics, such as FAI, BMI, cycle history (oligomenorrhea or
      amenorrhea), and mean ovarian volume. These observations may add to ongoing
      discussion regarding etiological factors involved in ovarian dysfunction in these
      patients and classification of normogonadotropic anovulatory infertile women.

PMID- 9661610
TI  - Calcium-regulated renal calcium handling in healthy men: relationship to sodium
      handling.
AB  - Several studies have shown an increase in urinary calcium excretion in response
      to a calcium load. However, because of the inverse changes in PTH levels with a
      calcium load, the effect of changes in serum calcium per se on its own excretion
      is unclear in humans. In this study we used a PTH clamp protocol to further
      characterize calcium-regulated renal calcium and magnesium handling and the
      relationship of the former to sodium excretion. Eight normal male subjects were
      evaluated using a calcium clearance protocol with graded calcium infusions under
      a PTH clamp while in balance during a high and then during a low sodium diet. The
      curves describing calcium and magnesium excretion as a function of serum ionized
      calcium on the high sodium diet were best fitted by sigmoidal functions, with
      midpoints (the levels of calcium resulting in half-maximal increases in urinary
      cation excretion) of 1.51 and 1.49 mmol/L, respectively. The curve describing
      urinary sodium as a function of serum calcium was also sigmoidal on the high
      sodium diet, with a midpoint of 1.55 mmol/L. Our data taken in conjunction with
      those of previous studies evaluating sodium and calcium excretion in diseases
      characterized by inactivating or activating mutations in the calcium receptor,
      are consistent with the hypothesis that PTH-independent, calcium-dependent
      changes in renal calcium, magnesium, and sodium handling may be mediated at least
      in part by this receptor, which is known to be located in the loop of Henle.

PMID- 9661611
TI  - Stature in Ecuadorians heterozygous for growth hormone receptor gene E180 splice
      mutation does not differ from that of homozygous normal relatives.
AB  - Heterozygosity for certain mutations of the GH receptor (GHR) gene has been
      proposed as the cause of partial resistance to GH, and there has been a recent
      demonstration of a dominant-negative effect of such a mutation in a mother and
      child. To examine the effect of heterozygosity in a large genetically homogeneous
      population with GHR deficiency, in which a substantial number of heterozygous
      (carrier) subjects and homozygous normal individuals can be compared, we studied
      a population in Ecuador in which 70 individuals with GHR deficiency were
      homozygous for the E180 splice mutation. We found that 58 heterozygous relatives
      of probands were not significantly shorter than 37 homozygous normal relatives
      [SD score (SDS) for height -1.85 +/- 1.04 (SD) vs. -1.55 +/- 0.96, P > 0.10].
      When only those families with both homozygous normals and carriers were compared,
      the 33 heterozygous and 29 normal relatives did not differ significantly in
      height SDS (-1.98 +/- 1.07 vs. -1.77 +/- 0.91, P > 0.3). If heterozygosity for
      the E180 splice mutation were to influence stature, heights of heterozygous
      parents of probands would be expected to correlate with those of probands and of
      carriers who are their offspring and not with heights of their homozygous normal
      children. Parental height SDS did not correlate with height SDS of affected
      offspring (r = 0.24). For unaffected siblings as a group or analyzed separately
      as normals or carriers, there was a strong correlation between parental and
      offspring SDS for height (P < 0.01 for all comparisons). Thus, the effect of
      homozygosity for the GHR mutation was so profound as to abolish parental
      influence on height, and there was no difference in the influence of parental
      stature between carrier and noncarrier offspring. These findings demonstrate no
      meaningful effect on stature of heterozygosity for the E180 splice mutation of
      the GHR, which is a functional null mutation and, in the homozygous state,
      results in profound short stature from severe insulin-like growth factor-I
      deficiency.

PMID- 9661612
TI  - Serum leptin levels in male marathon athletes before and after the marathon run.
AB  - Leptin is a hormone produced by the adipocytes to regulate food intake and energy
      expenditure at the hypothalamic level. It is commonly accepted that the main
      determinants of leptin secretion are the net amount of body fat and the mean size
      of adipocytes. On the contrary, important vectors of energy flux in the organism,
      such as food intake and energy expended on exercise, are not thought to be
      regulators of that secretion. To understand whether leptin is regulated by an
      acute energy expenditure such as strenuous exercise, 29 male athletes who had
      trained for marathon running were studied before and after a marathon run and
      compared with 22 nonobese, age-, sex-, and body mass index (BMI)-matched
      sedentary controls. Controls and marathon athletes showed no differences in BMI
      or fat-free mass. Marathon runners showed a strong reduction in total fat mass
      (6.2 +/- 0.4 kg; 9.1 +/- 0.5% of body fat) compared with controls (12.3 +/- 0.5
      kg; 16.1 +/- 0.5% of body fat; P < 0.05). This difference in body composition was
      paralleled by a mean serum leptin level that in marathonians (2.9 +/- 0.2
      micrograms/L) was significantly (P < 0.05) reduced compared with that in controls
      (5.1 +/- 0.6 micrograms/L). It is remarkable that the ratio of leptin per kg body
      fat, showed a very good agreement between the two groups, 0.40 +/- 0.04
      microgram/L.kg for controls and 0.46 +/- 0.03 microgram/L.kg for marathonians. In
      the two groups, leptin was correlated with both body weight, BMI, and fat mass (P
      < 0.001). The marathon trajectory was the standard 42.195 km accomplished in an
      average time of 3 h, 17 min, 7 s, with a calculated energy expenditure of over
      2800 Cal. After the marathon run, a water imbalance occurred, with a significant
      decrease in body weight and an increase in serum albumin. A significant (P <
      0.05) reduction in leptin values was observed after the run (2.6 +/- 0.2
      micrograms/L) compared with before (2.9 +/- 0.2 micrograms/L), which was more
      relevant considering the relative hemoconcentration. In conclusion, 1) compared
      with sedentary subjects, leptin levels are reduced in male marathon runners in
      parallel with the relevant reduction in total body fat; 2) expressed as a ratio
      of leptin per kg body fat, no differences were observed between marathonians and
      controls; and 3) after an energy expenditure of 2800 Cal in the marathon run, a
      reduction in leptin levels occurred. Strong changes in energy expenditure may
      regulate serum leptin levels in man.

PMID- 9661613
TI  - Retinal changes mimicking diabetic retinopathy in two nondiabetic, growth hormone
      treated patients.
AB  - A role for GH in the pathogenesis of diabetic retinopathy has long been
      postulated. Previous clinical studies, however, have been confounded by
      hyperglycemia. We have identified 2 cases of retinopathy associated with
      exogenous GH therapy in nondiabetic patients. Cases were identified through the
      MedWatch drug surveillance system of the U.S. Food and Drug Administration.
      Causality by concomitant medications was excluded by a search of the literature
      and the FDA data base. The first patient, an obese, 31-yr-old male with traumatic
      hypothalamic injury, presented with nonproliferative retinopathy and macular
      edema, resulting in decreased visual acuity (OD 20/40-1; OS count fingers), which
      required laser surgery. Human GH had been initiated at 0.009 mg/ kg.day, 14
      months earlier, and titrated to 0.017 mg/kg.day. The second patient, a nonobese,
      11-yr-old girl receiving GH for the management of short stature in Turner's
      Syndrome, presented with neovascularization. GH doses were 0.033 mg/kg.day for
      the first 17 months and 0.043 mg/ kg.day for the following 5 months. Cumulative
      laboratory and clinical observations suggest that GH and related peptides have a
      role in retinal pathology independent of the degree of glucose tolerance.

PMID- 9661614
TI  - Secondary hyperparathyroidism in a patient with eight parathyroid glands.
AB  - The etiology of secondary hyperparathyroidism is multifactorial, and as many as
      10% of patients will ultimately require surgical intervention. This condition is
      most commonly caused by four-gland hyperplasia. We describe a patient who
      presented with secondary hyperparathyroidism and symptoms of memory loss,
      pruritus, constipation, and bone and joint pain. These complaints could not be
      controlled with conventional therapy. Over a three-year period, the patient
      underwent three neck explorations, with complete and persistent relief of his
      symptoms following the last parathyroidectomy. A total of eight parathyroid
      glands were removed during these three procedures. Although recurrence of
      hyperparathyroidism can be caused by seeding at the time of operation, the glands
      removed during the second and third procedures were not the typical miliary
      seeding seen with this complication. These glands were solid and hypertrophied
      and were found in areas not previously explored. A discussion of the possible
      causes of this unusual presentation is included.

PMID- 9661615
TI  - Use of an ultrasensitive recombinant cell bioassay to determine estrogen levels
      in girls with precocious puberty treated with a luteinizing hormone-releasing
      hormone agonist.
AB  - Although treatment of girls with precocious puberty should ideally restore
      estradiol levels to the normal prepubertal range, treatment effectiveness has
      usually been monitored by gonadotropin levels because estradiol RIAs have lacked
      sufficient sensitivity to monitor treatment effectiveness. We hypothesized that a
      recently developed ultrasensitive recombinant cell bioassay for estradiol would
      have sufficient sensitivity to demonstrate a dose-dependent suppression of
      estradiol during LH-releasing hormone agonist treatment and to determine whether
      currently used doses are able to suppress estradiol levels to the normal
      prepubertal range. Twenty girls with central precocious puberty were assigned
      randomly to receive deslorelin for 9 months at a dose of 1, 2, or 4 micrograms/
      kg.day. A significant dose-response relationship was observed, with mean +/- SD
      estradiol levels of 16.7 +/- 6.1, 7.9 +/- 1.6, and 6.5 +/- 0.7 pmol/L at the
      doses of 1, 2, and 4 micrograms/kg.day, respectively (P < 0.01). The highest dose
      suppressed estradiol levels to just above the 95% confidence limits for normal
      prepubertal girls (< 0.07-6.3 pmol/L). We conclude that the ultrasensitive
      bioassay for estradiol has sufficient sensitivity for monitoring the response to
      LH-releasing hormone agonist treatment of central precocious puberty.
      Additionally, the observation that the deslorelin dose of 4 micrograms/kg.day did
      not fully restore estradiol levels to the normal prepubertal range suggests that
      some girls with precocious puberty may require higher doses to receive the
      maximal benefit of treatment. We suggest that restoration of estradiol levels to
      the normal prepubertal range should be the ultimate biochemical measure of
      efficacy, as estradiol is the key hormone that accelerates growth rate, bone
      maturation rate, and breast development in girls with precocious puberty.

PMID- 9661616
TI  - Pituitary-adrenal suppression in preterm, very low birth weight infants after
      inhaled fluticasone propionate treatment.
AB  - Systemic corticosteroids prescribed for treatment of pulmonary diseases in
      preterm, very low birth weight infants caused severe suppression of the
      hypothalamic-pituitary-adrenal axis and produced serious physiological and
      metabolic disturbances. However, the effect of inhaled corticosteroids on their
      pituitary-adrenal functions is not known. We prospectively evaluate the pituitary
      adrenal function using the human CRH stimulation test in a cohort of very low
      birth weight infants at risk for hypothalamic-pituitary-adrenal axis suppression
      in a double blind, randomized pilot study designed for assessing the efficacy and
      adverse effects of inhaled fluticasone propionate in newborn preterm infants who
      required mechanical ventilation for treatment of respiratory distress syndrome.
      Twenty-five preterm (< 32 gestational weeks), very low birth weight (< 1500 g)
      infants were randomized to receive inhaled fluticasone propionate (n = 13) or a
      placebo inhaler (n = 12). The medication was given every 12 h (fluticasone
      propionate, 1,000 micrograms/day) for 14 days. All surviving infants had their
      pituitary-adrenal functions assessed by human CRH test on the following morning
      immediately after completion of the 2-week course. All basal (0 min) and post
      stimulation (15, 30, and 60 min) plasma ACTH and serum cortisol concentrations
      were significantly suppressed in the inhaled fluticasone group compared to their
      corresponding levels in the placebo group [basal plasma ACTH concentrations (F =
      6.0; P = 0.02), poststimulation plasma ACTH concentrations (F > 8.6; P < 0.01),
      basal serum cortisol concentrations (F = 5.6; P = 0.03), and poststimulation
      serum cortisol concentrations (F > 15.6; P < 0.001)]. This is the first study in
      very low birth weight infants that demonstrates unequivocally that cumulative
      high dose inhaled corticosteroids can induce moderately severe suppression of
      both the pituitary and adrenal glands. The systemic bioactivity is probably
      associated with pulmonary vascular absorption, which effectively circumvents the
      hepatic first pass metabolism. Until the question of safety can be adequately
      addressed, inhaled fluticasone propionate should be used with cautionin preterm
      infants.

PMID- 9661617
TI  - Decline in insulin-like growth factor I levels after clomiphene citrate does not
      correct hyperandrogenemia in polycystic ovary syndrome.
AB  - It is widely accepted that the action of clomiphene citrate (CC) is mediated
      through its antiestrogenic properties on the hypothalamic-pituitary axis.
      Although insulin-like growth factor I (IGF-I) enhances the thecal cell response
      to LH, and estrogen treatment is associated with a reduction in IGF-I levels, CC
      is known to decrease circulatory IGF-I levels in polycystic ovary syndrome (PCOS)
      patients. The impact of lowering IGF-I levels on androgen levels in PCOS is
      unknown. This study was designed to examine the impact of CC treatment on the
      interrelationships of IGF-I, androgens, and estrogens in normal subjects and
      patients with PCOS. IGF-I, gonadotropin, androgen, estrogen, and sex hormone
      binding globulin levels were measured in 8 PCOS patients and 10 normal subjects
      before and after treatment with the antiestrogen CC. Studies were performed in
      the early follicular phase, days 4-6 of the menstrual cycle in normal subjects.
      In normal subjects, CC treatment led to a significant increase in estradiol (84
      +/- 10 to 234 +/- 62 pmol/L, untreated and CC treated; P < 0.05) and estrone (125
      +/- 14 to 257 +/- 29 pmol/L; P < 0.05) levels with a significant lowering of IGF
      I levels (297 +/- 25 to 230 +/- 17 micrograms/L; P < 0.05). Similarly, in PCOS
      patients a significant increase in estradiol (110 +/- 11 to 245 +/- 58 pmol/L; P
      < 0.05) and estrone (301 +/- 32 to 401 +/- 90 pmol/L; P < 0.05) levels and a
      significant lowering of IGF-I levels (330 +/- 43 to 214 +/- 27 micrograms/L; P <
      0.05) were observed after CC treatment. However, no significant correlation was
      observed between changes in IGF-I and changes in estradiol in either group.
      Compared to pretreatment levels, no significant changes in the following
      parameters were observed after 5 days of CC treatment in either study group:
      testosterone, testosterone/sex hormone-binding globulin ratio, and
      androstenedione. The relationship among CC treatment, gonadotropin, estrogen, and
      IGF-I levels is complex. Changes in blood IGF-I levels are not associated with
      changes in androgen levels, although paracrine and or autocrine effects cannot be
      excluded.

PMID- 9661618
TI  - Insulinotropic hormone glucagon-like peptide-1-(7-37) appears not to augment
      insulin-mediated glucose uptake in young men during euglycemia.
AB  - Glucagon-like peptide-1 (GLP-1) is an intestinal insulinotropic hormone that
      augments insulin secretion in response to meals and lowers blood glucose levels
      in both type 1 and type 2 diabetic subjects. It has been proposed that a
      substantial component of the glucose-lowering effects of GLP-1 occurs via insulin
      independent mechanisms. However, the interpretations of the studies have been
      controversial. This study was conducted to examine whether glucagon-like peptide
      (GLP-1) has an insulin-like effect during euglycemia. Nine young lean men (age,
      25 +/- 1.4 yr; body mass index, 24.0 +/- 0.7 kg/m2) volunteered to participate in
      two euglycemic clamp studies (n = 18 clamps) for 120 min. The initial clamp was
      performed with a primed continuous infusion of GLP-1 at a final rate of 1.5
      pmol/kg.min from 0-60 min. At 60 min, the GLP-1 infusion was terminated, and
      euglycemia was maintained from 60-120 min. After the GLP-1 study, each
      individual's plasma insulin level was measured. A second study was performed that
      was identical to the first, with the infusion of regular insulin in place of GLP
      1. Insulin infusion rates were designed in each individual to simulate plasma
      insulin levels produced during the GLP-1 infusion. The rate of disappearance of
      glucose was calculated for each subject. Basal plasma insulin levels were similar
      between studies and averaged 49 +/- 5 pmol/L. Basal GLP-1 levels were also
      similar (6.0 +/- 1.0 pmol/L). In response to the GLP-1 infusion, although basal
      plasma glucose levels were clamped, significant increases in insulin occurred in
      all subjects (P < 0.001). With the nearly identical plasma insulin levels during
      the two studies (30-60 min levels: GLP-1 study, 151 +/- 48; insulin study, 146 +/
      31 pmol/L), the rate of disappearance of glucose progressively increased in
      response to both GLP-1 and insulin infusions, but was not significantly different
      between the studies. The design of the study necessitated conducting the GLP-1
      study first, which may have been accompanied by a greater stress than the second
      study. We, therefore, measured cortisol levels. Basal cortisol (and ACTH) levels
      were not different. However, cortisol levels significantly increased during the
      GLP-1 infusions, and this was preceded by an increase in ACTH levels.
      Somatostatin levels were not different either basally or during the clamps. We
      conclude that in the euglycemic state, an acute infusion of GLP-1 does not have
      insulin-like effects in lean nondiabetic men. Intravenous administration of GLP-1
      activates hypothalamic neuroendocrine neurons.

PMID- 9661619
TI  - Modifications induced by plasma from insulin-dependent diabetic patients and by
      lysophosphatidylcholine on human Na+,K(+)-adenosine triphosphatase.
AB  - To investigate the molecular mechanisms of the inhibition of Na+,K(+)-adenosine
      triphosphatase (Na+,K(+)-ATPase) in diabetes mellitus, we incubated Na+,K(+)
      ATPase purified from human placenta of six healthy nondiabetic women with plasma
      from six insulin-dependent diabetic (IDDM) men and six healthy controls and with
      different concentrations of lysophosphatidylcholine (LPC). We determined the
      enzyme activity, anthroyl ouabain-binding capacity, dissociation constant (Kd),
      and average lifetime values (tau) by the static and dynamic fluorescence of
      anthroyl ouabain. The lipid annulus of the enzyme was studied by static and
      dynamic fluorescence of 1-(4-trimethylamino-phenyl)-6-phenyl-1,3,5-hexatriene
      (TMA-DPH). Moreover, we studied the lipid microenvironment surrounding the
      Na+,K(+)-ATPase purified from the placentas of six healthy women and six insulin
      dependent diabetic women, determining the percent composition of phospholipids of
      the lipid annulus. The addition of total and protein-free IDDM plasma to normal
      Na+,K(+)-ATPase significantly inhibited the enzymatic activity even at the lowest
      concentration studied (1: 100), whereas the ouabain-binding capacity, Kd, and tau
      were not affected by IDDM plasma. The fluorescence polarization and lifetime
      values of TMA-DPH were significantly decreased by diabetic plasma. The incubation
      of Na+,K(+)-ATPase with LPC caused an inhibition of the enzymatic activity
      without modifications of the anthroyl ouabain-binding capacity and dissociation
      constant. The fluorescence polarization and lifetime values of TMA-DPH were
      significantly decreased by 5 mumol/L LPC. The study of the phospholipids
      surrounding Na+,K(+)-ATPase demonstrated a significant increase in the percent
      LPC content in IDDM patients compared with controls together with a concomitant
      decrease in phosphatidylcholine. These observations indicate that the inhibition
      caused by diabetic plasma on Na+,K(+)-ATPase is not dependent on a modification
      of the ouabain-binding site and that it seems to mimic the effect of LPC
      addition. A link between modification of the lipid moiety of the enzyme and
      Na+,K(+)-ATPase inhibition might be hypothesized.

PMID- 9661620
TI  - Separate and interactive regulation of cytochrome P450 3A4 by triiodothyronine,
      dexamethasone, and growth hormone in cultured hepatocytes.
AB  - CYP3A4, the predominant cytochrome P450 expressed in human liver, is responsible
      for the metabolism of endogenous steroids and many drugs. On the basis of
      pharmacokinetic studies in patients with hormonal derangements and the effects of
      replacement therapy, it has been suggested that iodothyronines decrease CYP3A4
      mediated drug metabolism, whereas glucocorticoids and GH enhance CYP3A4 activity.
      The aim of the present study, using well differentiated human hepatocytes in
      primary culture, was to examine directly whether hormonal factors regulate CYP3A4
      gene expression. Addition of T3 to primary hepatocytes resulted in a marked
      reduction of CYP3A4-catalyzed testosterone 6 beta-hydroxylase activity and
      corresponding levels of CYP3A4 protein and messenger ribonucleic acid compared to
      those in untreated cells. Conversely, both dexamethasone and GH treatment
      substantially increased CYP3A4 gene expression. None of the hormones studied
      consistently altered the expression of other human cytochrome P450 genes. We
      conclude that iodothyronines, glucocorticoids, and GH act directly on human
      hepatocytes to regulate the expression of CYP3A4, and these effects appear to be
      exerted at a pretranslational level. Altered regulation of hepatic CYP3A4 is,
      therefore, likely to account for previous observations concerning the effects of
      endocrine diseases and hormonal treatments on human cytochrome P450-mediated drug
      and steroid metabolism.

PMID- 9661621
TI  - Somatostatin and somatostatin receptor subtype gene expression in medullary
      thyroid carcinoma.
AB  - The possible existence of an autocrine/paracrine role for SRIF in normal and
      neoplastic thyroid parafollicular C cells has supported the use of SRIF analogues
      in the treatment of patients with medullary thyroid carcinoma (MTC). In this
      study, we have investigated the expression of SRIF by immunohistochemistry and RT
      PCR, and the expression of SRIF receptor (SSTR) subtypes by RT-PCR, in a series
      of 14 MTCs. SRIF messenger RNA was detected in all cases, although immunoreactive
      cells were only identified in 8. SSTR messenger RNA was present in 12 out of the
      14 tumors. Expression of more than 1 SSTR subtype was detected in 10 tumors.
      SSTR2, the subtype that preferentially binds to the SRIF analogue octreotide, was
      the subtype most frequently detected, whereas SSTR4 was not detected in any case.
      These results confirm the frequent expression of both SRIF and its receptors in
      MTC. The presence of different combinations of SSTR subtypes in a given patient
      may explain the variable clinical response to SRIF analogues and may promote the
      search for more selective drugs with different affinities to the various receptor
      subtypes.

PMID- 9661622
TI  - Localization of estrogen receptor-alpha in human and rabbit skeletal tissues.
AB  - Estrogen is essential for the development and maintenance of optimal bone mass in
      women and men, and acts through activation of estrogen receptors (ER). We have
      examined the pathways of estrogen action on the skeleton by seeking to localize
      the "classical" estrogen receptor, ER alpha, to particular cells to test the
      hypotheses that 1) estrogen directly influences growth plate chondrocytes; and 2)
      estrogen has a principal action on bone tissue via osteoblasts. ER alpha
      messenger ribonucleic acid (mRNA) was localized by in situ hybridization in human
      specimens from five males (11-15 yr old), two females (9 and 11 yr old), and
      three growing rabbits. In all of the human material examined, ER alpha mRNA was
      consistently identified in chondrocytes. In all of the rabbit tissue studied, ER
      alpha mRNA was localized in chondrocytes of the growth plate and the subarticular
      epiphyseal growth center. ER alpha mRNA signals were readily observed in both
      active osteoblasts and lining cells on trabecular surfaces of all samples. No
      clear evidence of positive staining was detectable in osteoclasts or osteocytes
      in either species. The distribution of ER alpha mRNA coincided with
      immunolocalization of the ER protein in the human specimens. These data suggest a
      direct action of estrogen on growth plate chondrocytes that may affect
      longitudinal growth and subsequent fusion of the growth plate and also on
      osteoblasts to affect bone formation at trabecular sites.

PMID- 9661623
TI  - Interleukin-1 beta enhances interleukin-1 receptor antagonist content in human
      somatotroph adenoma cell cultures.
AB  - In addition to the well-known modulation of immune and inflammatory responses,
      the interleukin-1 (IL-1) system has been shown to be involved in the regulation
      of anterior pituitary hormone secretion and growth. We previously demonstrated
      that IL-1 receptor antagonist (IL-1ra) is expressed in human pituitary adenomas
      cultured in vitro. In the present study, we investigated the regulation of IL-1ra
      protein by IL-1 beta (1-100 U/mL) in human somatotroph adenomas (n = 9) cultured
      for 12-48 h. IL-1 beta significantly enhanced the concentration of IL-1ra dose
      dependently in the somatotroph adenoma cell lysates, whereas IL-1ra
      concentrations remained unchanged in the culture supernatants. Furthermore, basal
      IL-1ra concentrations were significantly higher in the cell lysates compared with
      the corresponding culture supernatants. The regulation of IL-1ra in somatotroph
      adenoma cells is different from human cultured monocytes, in which IL-1 beta
      significantly stimulated IL-1ra secretion into the culture supernatants, and no
      change of intracellular IL-1ra content was observed. Incubation of the
      somatotroph adenoma cells with 100 U/mL IL-1 beta did not result in a change of
      GH concentrations in the culture supernatants. Enhancement of intracellular IL
      1ra protein by IL-1 beta may represent a mechanism intrinsic to somatotroph
      adenoma cells to counterregulate the response to IL-1 beta on hormone secretion
      or cellular growth.

PMID- 9661624
TI  - A unique constitutively activating mutation in third transmembrane helix of
      luteinizing hormone receptor causes sporadic male gonadotropin-independent
      precocious puberty.
AB  - Several constitutively activating mutations have been demonstrated in the sixth
      transmembrane helix of the human LH receptor (hLHR) in boys with gonadotropin
      independent precocious puberty. In the current study, we examined two unrelated
      Brazilian boys with gonadotropin-independent precocious puberty caused by two
      different heterozygous activating mutations of the hLHR. Direct sequencing of the
      entire exon 11 of the hLHR revealed a heterozygous substitution of T for G at
      nucleotide 1370, that converts Leu 457 to Arg in the third transmembrane helix of
      the hLHR in one affected boy. His biological parents had a normal hLHR gene
      sequence, establishing the sporadic nature of this novel Leu457Arg mutation.
      Human embryonic 293 cells expressing hLHR mutant (L457R) or hLHR wild-type bound
      CG with high affinity. However, cells expressing hLHR(L457R) exhibited
      significantly higher basal levels of cAMP (7- to 14-fold) than cells expressing
      the wild-type receptor, indicating constitutive activation of hLHR(L457R). Basal
      levels of cAMP in hLHR(L457R)-expressing cells were, nonetheless, not as great as
      the levels of cAMP produced by hLHR wild-type-expressing cells incubated with a
      saturating concentration of CG. Furthermore, cells expressing hLHR(L457R) were
      unresponsive to further stimulation by CG. This finding was confirmed in the
      patient by lack of an increase in serum testosterone after CG stimulation. These
      results suggest that the conformation of hLHR(L457R) mutant represents a
      different activated receptor state (R*) than the agonist-occupied wild-type
      receptor. We also identified the previously described Ala568Val mutation in the
      third intracellular loop of the LHR in the other affected African-Brazilian boy
      and his normal prepubertal sister, suggesting the inherited form of precocious
      puberty in this boy. We conclude that the third transmembrane helix is a
      potential area for activating mutations of the hLHR that cause male precocious
      puberty.

PMID- 9661625
TI  - Meta-analysis of the association of Trp64Arg polymorphism of beta 3-adrenergic
      receptor gene with body mass index.
AB  - A possible pathogenic polymorphism in the beta 3-adrenergic receptor gene
      (Trp64Arg) has been reported to be associated with increased body weight,
      clinical features of insulin resistance, and early development of type 2 diabetes
      mellitus in several populations. However, such findings have not been consistent
      among studies, making the hypothesis that this genetic marker is associated with
      clinical features controversial. To assess the effect of the genotypes on body
      mass index (BMI), we performed a meta-analysis of the data from the literature
      using an extension of ANOVA for continuous measures. In a total of 48 subgroups
      containing subjects with (n = 2447) and without (n = 6789) the Trp64Arg variant,
      the summary weighted mean difference in BMI was 0.30 (95% confidence interval,
      0.13-0.47) kg/m2, indicating that variant carriers exhibited higher BMI (on the
      average, 0.30 kg/m2 higher) than normal homozygous subjects. In this case, there
      was no significant evidence against homogeneity of the effect (P = 0.36). This is
      the first meta-analysis assessing quantitative phenotypes in relation to a
      genetic polymorphism, and the results support the hypothesis that the Trp64Arg
      polymorphism is associated with BMI across diverse population groups, suggesting
      that the beta 3-adrenergic receptor gene locus plays a role in genetic
      predisposition to increased body weight in a universal manner.

PMID- 9661626
TI  - Differential changes in free and total insulin-like growth factor I after major,
      elective abdominal surgery: the possible role of insulin-like growth factor
      binding protein-3 proteolysis.
AB  - Major surgery is accompanied by extensive proteolysis of insulin-like growth
      factor (IGF)-binding protein-3 (IGFBP-3). Proteolysis of IGFBP-3 is generally
      believed to increase IGF bioavailability due to a diminished affinity of the
      IGFBP-3 fragments for IGFs. We have investigated 18 patients undergoing elective
      ileo-anal J-pouch surgery. Patients were randomized to treatment with GH (12
      IU/day; n = 9) or placebo (n = 9) from 2 days before to 7 days after operation.
      Free IGF-I and IGF-II were measured by ultrafiltration of serum, and IGFBP-3
      proteolytic activity was determined by a [125I]recombinant human IGFBP-3
      degradation assay. In the GH-treated group, total IGF-I increased preoperatively
      by 99%. Postoperatively, total IGF-I decreased by 48% (placebo) and 52% (GH).
      Immunoassayable IGFBP-3 decreased by 27% (placebo) and 26% (GH). In the placebo
      treated group, free IGF-I was unchanged throughout the study. In the GH-treated
      group, free IGF-I increased by 277% preoperatively and remained elevated after
      operation. IGFBP-3 proteolytic activity increased by 63-73% after operation. The
      relative elevations of free IGF-I levels despite decreased total IGF-I levels
      could thus relate to augmented IGFBP-3 proteolysis.

PMID- 9661627
TI  - Uncoupling protein-2 messenger ribonucleic acid expression during very-low
      calorie diet in obese premenopausal women.
AB  - Uncoupling protein-2 (UCP2) is a mitochondrial protein expressed in a wide range
      of human tissues. By uncoupling respiration from ATP synthesis, UCP2 might be
      involved in the control of energy expenditure. We have investigated UCP2 gene
      expression in human adipose tissue. In eight subjects, we found a positive
      correlation (r = 0.91, P < 0.002) between subcutaneous and visceral fat depots
      UCP2 messenger RNA (mRNA) levels, suggesting that UCP2 mRNA level in subcutaneous
      adipose tissue is a good index of UCP2 gene expression in whole body adipose
      tissues. The effect of a 25-day very-low-calorie diet un UCP2 mRNA level and
      resting metabolic rate was investigated in eight obese premenopausal women. There
      was no difference in UCP2 mRNA levels before and during the diet. After 25 days
      of hypocaloric diet, a positive correlation was found between adipose tissue UCP2
      mRNA level and resting metabolic rate adjusted for lean body mass (r = 0.82, P <
      0.01). These results show that very-low-calorie diet, unlike short-term fasting,
      is not associated with an induction in UCP2 mRNA expression, and that adipose
      tissue UCP2 mRNA levels may be related to variations in resting energy
      expenditure in humans.

PMID- 9661628
TI  - Stress and the menstrual cycle: relevance of cycle quality in the short- and long
      term response to a 5-day endotoxin challenge during the follicular phase in the
      rhesus monkey.
AB  - The notion that stress activates central and peripheral pathways to inhibit the
      menstrual cycle is well accepted, but the initial processes through which this
      occurs have not been investigated. This study uses a relevant nonhuman primate
      model to document the cyclic endocrine effects imposed by a moderate short-term
      stress episode in the follicular phase. The stress paradigm is a 5-day
      inflammatory/immune-like challenge produced by the administration of bacterial
      endotoxin [lipopolysaccharide (LPS)], which, through the release of endogenous
      cytokines and other mediators, induces a physiopathological response similar to a
      bacterial infection. LPS was administered iv twice daily for 5 days starting on
      days 2-8 of the follicular phase. The stress challenge resulted in a significant
      lengthening of the follicular phase in all monkeys. Two distinct groups were
      observed. In group 1 (n = 5), the mean (+/- SE) length of the follicular phase in
      the LPS-treated cycle was significantly increased, from 10.2 +/- 0.2 in control
      cycle 2 to 30.8 +/- 4.3 days (except in one monkey that had a 4-month amenorrheic
      interval). In group 2 (n = 5), the length of the follicular phase significantly
      increased but not to exceed the duration of the LPS treatment (9.7 +/- 1.1 vs.
      13.6 +/- 1.2). Estradiol concentrations decreased significantly after LPS in
      group 1 (34.8 +/- 5.5 vs. 16.2 +/- 6.5 pg/mL) and remained suppressed after the
      challenge. In group 2, estradiol levels remained stationary throughout the 5-day
      LPS treatment (26.0 +/- 6.5 vs. 25.6 +/- 3.9). Compared with control values at a
      similar stage of the follicular phase, most LH and FSH values during LPS
      treatment were higher than controls. Estradiol and gonadotropin surges were
      delayed by LPS treatment for a varying length of time according to each grp.
      Significant differences in integrated luteal progesterone concentrations
      characterized control cycles of groups 1 and 2 (group 1: 36.5 +/- 1.5, group 2:
      47.5 +/- 2.6). In group 1, there were no further effects of LPS on luteal
      progesterone during the treatment and two post-LPS cycles. In contrast, in group
      2, integrated luteal progesterone concentrations were significantly decreased in
      post-LPS cycle 1 (to 36.0 +/- 4.4). Cortisol significantly increased at hour 3
      after each morning LPS injection but the amplitude of the response decreased over
      the 5-day period. Progesterone increased significantly by hour 3 after the first
      LPS injection but remained unchanged after subsequent LPS administration. Our
      data demonstrate that a 5-day inflammatory-like episode during the follicular
      phase can delay folliculogenesis and that damage to this process is intensified
      in individuals who already demonstrate a subtle cyclic degradation, in the form
      of decreased progesterone secretion in the luteal phases preceding the stress
      episode. Long-term endocrine effects, in the form of decreased luteal secretory
      activity in the first poststress cycle, are observed in normally cycling
      individuals, suggesting that inadequacy of the luteal phase may represent the
      first stage in the damage that a stress episode can inflict upon the normal
      menstrual cycle.

PMID- 9661629
TI  - Overnight normalization of glucose concentrations improves hepatic but not
      extrahepatic insulin action in subjects with type 2 diabetes mellitus.
AB  - Subjects with poorly controlled type 2 diabetes are both hyperglycemic and
      insulin resistant. To determine whether short term restoration of normoglycemia
      improves insulin action, hyperinsulinemic (approximately 300 pmol/L) euglycemic
      clamps were performed in diabetic subjects after either overnight infusion of
      saline or overnight infusion of insulin in amounts sufficient to maintain
      euglycemia throughout the night. Fasting glucose concentrations (5.2 +/- 0.2 vs.
      11.9 +/- 1.4 mmol/L; P < 0.01) and rates of endogenous glucose production (13.0
      +/- 1.1 vs. 18.6 +/- 1.6 mumol/kg.min; P < 0.05) were both lower after overnight
      insulin than overnight saline. Insulin-induced stimulation of glucose uptake (to
      34.9 +/- 6.8 vs. 28.8 +/- 3.4 mumol/kg.min; P = 0.2) and inhibition of free fatty
      acids (to 0.13 +/- 0.03 vs. 0.12 +/- 0.04 mmol/L; P = 0.6) did not differ after
      overnight saline and overnight insulin. In contrast, endogenous glucose
      production during the final hour of the hyperinsulinemic clamps (i.e. when
      glucose concentrations were the same) remained higher (P = 0.05) after overnight
      saline than after overnight insulin (5.5 +/- 1.5 vs. 0.02 +/- 1.4 mumol/kg.min).
      Thus, acute restoration of euglycemia by means of an overnight insulin infusion
      improves hepatic (and perhaps renal) but not extrahepatic insulin action.

PMID- 9661630
TI  - The effect of luteal "rescue" on the expression and localization of matrix
      metalloproteinases and their tissue inhibitors in the human corpus luteum.
AB  - Luteolysis is associated with tissue remodeling probably involving the matrix
      metalloproteinases (MMPs) and their specific tissue inhibitors (TIMPs). This
      study investigated the expression and localization of the major MMPs and TIMPs in
      the human corpus luteum throughout the luteal phase and after luteal rescue with
      hCG. Corpora lutea (n = 9) were collected at hysterectomy and were dated by
      serial urinary LH estimation. In addition, corpora lutea (n = 3) were collected
      from women who had received daily doubling doses of hCG to mimic the hormonal
      changes of early pregnancy. MMP-1, MMP-2, MMP-9, TIMP-1, TIMP-2, and TIMP-3 were
      investigated by zymography, reverse zymography, Northern blotting, and in situ
      hybridization. There was no change in the expression of MMP-1, TIMP-1, and TIMP-2
      throughout the luteal phase or after luteal rescue. Little TIMP-3 could be
      detected in the corpus luteum. MMP-9 activity peaked in the early and late luteal
      phase. The expression and activity of MMP-2 were maximal in the late luteal
      phase. Exposure to hCG during luteal rescue in vivo was associated with a
      reduction (P < 0.05) in the expression and activity of MMP-2. Messenger
      ribonucleic acids (mRNAs) for MMP-1, MMP-2, and TIMP-2 were localized to the
      connective tissue stroma and the thecal-lutein cells of the corpus luteum. In
      contrast, TIMP-1 mRNA was localized to the granulosa-lutein cells, and MMP-9 mRNA
      was expressed in scattered cells within the steroidogenic and nonsteroidogenic
      cell layers. In conclusion, during maternal recognition of pregnancy, hCG
      prevents the normal increase in MMP-2 in the late luteal phase. MMPs can function
      in an environment containing large amounts of TIMP-1, as they have a different
      cellular localization.

PMID- 9661631
TI  - Androgen receptor gene expression in the primate ovary: cellular localization,
      regulation, and functional correlations.
AB  - Excess androgens are associated with a characteristic polyfollicular ovarian
      morphology; however, it is not known to what extent this problem is due to direct
      androgen action on follicular development vs. interference with gonadotropin
      release at the level of the pituitary or hypothalamus. To elucidate potential
      androgen effects on the ovary, we investigated the cellular localization of
      androgen receptor (AR) messenger ribonucleic acid (mRNA) in rhesus monkey using
      in situ hybridization. To investigate the regulation of ovarian AR gene
      expression, we compared the relative abundance of AR transcripts in monkeys
      during follicular and luteal phases of the menstrual cycle and in monkeys treated
      with testosterone. To assess potential functional consequences of AR expression
      in the primate ovary, we compared AR mRNA levels with indexes of follicular cell
      proliferation and apoptosis in serial sections from individual follicles. AR mRNA
      expression was most abundant in granulosa cells of healthy preantral and antral
      follicles in the primate ovary. Theca interna and stromal cells also expressed AR
      mRNA, but to a lesser degree than granulosa cells. No significant cycle stage
      effects were noted in AR mRNA levels; however, larger numbers of animals would be
      necessary to definitively establish a cycle stage effect. AR mRNA level was
      significantly increased in granulosa cells and was decreased in theca interna and
      stromal cells of testosterone-treated monkeys. Importantly, granulosa cell AR
      mRNA abundance was positively correlated with expression of the proliferation
      specific antigen Ki-67 (r = 0.91; P < 0.001) and negatively correlated with
      granulosa cell apoptosis (r = -0.64; P < 0.001). In summary, these data show that
      primate ovary AR gene expression is most abundant in granulosa cells of healthy
      growing follicles, where its expression is up-regulated by testosterone. The
      positive correlation between granulosa AR gene expression and cell proliferation
      and negative correlation with programmed cell death suggests that androgens
      stimulate early primate follicle development.

PMID- 9661632
TI  - Changes in the degree of sialylation of carbohydrate chains modify the biological
      properties of circulating thyrotropin isoforms in various physiological and
      pathological states.
AB  - Variation in asparagine-linked carbohydrate chains have a major impact on TSH
      biological properties. In particular, highly sialylated TSH is characterized by
      impaired intrinsic bioactivity and prolonged half-life. The aim of the present
      study was to investigate the changes in the degree of sialylation of circulating
      TSH isoforms that may occur in several physiological and clinical situations.
      Bioactivity and terminal sugar residues of immunopurified TSH were studied in 26
      normal adults (day- and nighttime serum pools), 2 cord serum pools from normal
      fetuses during the third trimester, 1 fetus with primary hypothyroidism (PH; 27th
      week), 1 fetus with resistance to thyroid hormone (RTH; 28th and 33rd weeks), 24
      patients with PH (before and during L-T4 treatment), and 5 patients with RTH
      before and during triiodothyrocetic acid (TRIAC) treatment. Nighttime TSH
      isoforms have an increased degree of sialylation compared to daytime TSH (35.8 +/
      9.7% vs. 23.8 +/- 5.8%; P < 0.03), thus accounting for the lower bioactivity
      [biological/immunological TSH ratio (TSH B/I), 1.3 +/- 0.4 vs. 2.0 +/- 0.2; P <
      0.0007]. In adult PH, TSH isoforms are highly sialylated (45.4 +/- 7.6%; P <
      0.007), showing an impaired bioactivity (0.7 +/- 0.3; P < 0.001). L-T4 therapy
      was accompanied by a trend toward normalization of TSH biological properties; TSH
      B/I was higher (1.0 +/- 0.3; P < 0.01), and the degree of sialylation was lower
      (36.8 +/- 7.0%; P < 0.02). A significant inverse correlation between TSH B/I
      values and the degree of sialylation was observed (P < 0.001). In normal fetuses,
      extremely bioactive asialo-TSH isoforms are circulating during the 3rd trimester.
      The impaired thyroid hormone action, such as that occurring in hypothyroid or RTH
      fetuses, induces an early expression of alpha-2,6-sialyltransferase activity
      within thyrotropes and results in the secretion of high amounts of sialylated TSH
      isoforms (34.6% and 26.3%). A hybrid TSH with peculiar terminal sugar residues
      and enhanced bioactivity is circulating in patients with RTH (TSH B/I, > or =
      2.2). Treatment with low doses of TRIAC can initially reduce thyroid hormone
      secretion in RTH, mainly through the secretion of TSH isoforms with changed
      terminal sugar residues and reduced bioactivity (TSH B/I, 0.9-1.7). In
      conclusion, changes in the terminal sialic acid residues modulate the biological
      properties of circulating TSH, play a relevant physiopathological role in various
      situations, and contribute to adjust thyroid-stimulating activity to temporary
      needs.

PMID- 9661633
TI  - Iodide symporter gene expression in human thyroid tumors.
AB  - Expression of the Na+/I- symporter (NIS) gene was investigated by RT-PCR in a
      selected series of 26 primary thyroid carcinomas (19 papillary, 5 follicular, and
      2 anaplastic). Fifteen follicular adenomas (11 "cold" and 4 "hot" adenomas) were
      also studied. Five of 19 papillary thyroid cancer did not express NIS messenger
      ribonucleic acid (mRNA). In all but 1 follicular cancer, NIS transcript was fully
      detected. In anaplastic tissue, NIS mRNA was only barely detected in 1 case. All
      of the follicular thyroid adenomas except 1 expressed the NIS gene. In contrast,
      all tumors studied excluding the anaplastic histotype fully expressed
      thyroglobulin and thyroid peroxidase mRNA transcripts. In 2 patients, a lower
      expression (3- to 5-fold) of NIS mRNA was found in metastasis by dot blot
      analysis compared with those in both normal and primary neoplastic thyroid
      tissue. Four of 8 differentiated thyroid cancer patients selected for the
      presence of metastases with negative posttherapy 131I total body scan showed the
      lack of NIS gene expression in their primary cancer. This defect, at least in
      these cases, is a somatic and intrinsic lesion of the primary cancer cells and is
      not due to a dedifferentiation process in the metastatic tissue. The early
      detection of the loss of NIS gene expression in the primary cancer, therefore,
      may provide useful information for the management of differentiated thyroid
      cancer patients.

PMID- 9661634
TI  - Familial hypoparathyroidism: identification of a novel gain of function mutation
      in transmembrane domain 5 of the calcium-sensing receptor.
AB  - Activating mutations of the extracellular calcium (Ca2+e)-sensing receptor (CaR)
      gene, mostly in its extracellular domain, can cause both familial and sporadic
      hypoparathyroidism. We report a Japanese family with severe hypoparathyroidism
      with pretreatment serum calcium (Ca) levels of 4.9-5.9 mg/dL. The proband
      presented with a seizure at 6 days of age. Her older brother and mother, who had
      also experienced seizures and tetany, respectively, likewise had
      hypoparathyroidism. A heterozygous missense mutation substituting a cysteine for
      the phenylalanine normally present at codon 788 (F788C) was identified in the
      CaR's fifth transmembrane domain and was shown to cosegregate with the disease.
      The mutation was absent in DNA from 50 control subjects. Analysis of the
      functional properties of the mutant receptor was carried out in transiently
      transfected HEK293 cells loaded with fura-2 by assessing Ca2+e-evoked increases
      in the cytosolic calcium concentration (Ca2+i). There was a leftward shift in the
      concentration-response curve for the mutant receptor [EC50 (effective
      concentration of Ca2+e producing half of the maximal Ca2+i response, 2.7 +/- 0.1
      vs. 4.1 +/- 0.1 mmol/L for the wild-type receptor]. HEK293 cells cotransfected
      with both the wild-type and mutant CaRs (to mimic the heterozygous state in
      affected family members) showed an EC50 (3.0 +/- 0.1 mmol/L) similar to that of
      the mutant CaR alone. Thus, we confirm that 1) a gain of function mutation in the
      fifth transmembrane domain of the CaR causes severe familial hypoparathyroidism
      by rendering the receptor more sensitive than normal to activation by Ca2+e; 2)
      some patients in the family do not experience seizures despite their severe
      hypocalcemia; and 3) this condition needs to be differentiated from other causes
      of hypoparathyroidism.

PMID- 9661635
TI  - Expression of Wilms' tumor suppressor gene (WT1) in term human trophoblast:
      regulation by cyclic adenosine 3',5'-monophosphate.
AB  - The Wilms' tumor suppressor gene (WT1), which is deleted in some Wilms' tumors,
      encodes a zinc finger transcription factor. We studied WT1 messenger ribonucleic
      acid (mRNA) in human term placenta and cytotrophoblasts differentiating into
      syncytiotrophoblasts in vitro by RT-PCR. The results suggest that WT1 mRNA is
      expressed in the trophoblasts in a cell-specific fashion. WT1 mRNA expression has
      been observed to decline remarkably in trophoblast cells after 72 h, when these
      cells are morphologically differentiated into multinucleated
      syncytiotrophoblasts. As it is well known that cAMP as a second messenger plays a
      significant role in cellular proliferation and differentiation of placental
      cells, we examined the effect of 8-bromo-cAMP on WT1 mRNA expression in
      undifferentiated cytotrophoblasts and differentiated syncytiotrophoblasts. We
      observed that cAMP enhanced WT1 mRNA expression in cytotrophoblasts, but remained
      ineffective in altering WT1 mRNA in syncytiotrophoblasts. In summary, the results
      of this investigation demonstrate that the WT1 gene is developmentally regulated
      during trophoblast differentiation. An involvement of the cAMP-mediated system in
      regulating the WT1 gene in the trophoblast is suggested.

PMID- 9661636
TI  - Postoperative induction of insulin-like growth factor binding protein-3
      proteolytic activity: relation to insulin and insulin sensitivity.
AB  - Increased serum insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3)
      proteolytic activity (IGFBP-3-PA) has been demonstrated in a number of clinical
      states of insulin resistance, including severe illness, after surgery, and in
      noninsulin-dependent diabetes mellitus. In the present study we assessed the role
      of insulin sensitivity in expression of IGFBP-3-PA in serum. In 18 patients
      studied, a significant increase in IGFBP-3-PA (P < 0.005) was demonstrated after
      colo-rectal surgery. Eight patients receiving an oral glucose load before surgery
      demonstrated a significant greater relative increase in IGFBP-3-PA compared with
      10 patients not receiving glucose (32.9 +/- 7.1% vs. 8.6 +/- 6.7%, respectively;
      P < 0.05). Both groups had reduced insulin sensitivity after surgery (-58 +/- 4%;
      P < 0.0001; n = 18), as determined by hyperinsulinemic, normoglycemic clamps;
      however, the group not receiving glucose displayed 18% less insulin sensitivity
      than the oral glucose load group (P < 0.05). Multiple regression analysis
      demonstrated that the relative changes in IGFBP-3-PA and C peptide levels were
      inversely correlated (P < 0.05), suggesting that increased IGFBP-3-PA, presumably
      increasing IGF bioavailability, may be associated with decreased insulin demands.
      Interestingly, insulin infusion during the 4-h hyperinsulinemic, normoglycemic
      clamp performed 24 h after surgery (post-op) resulted in a further increase in
      IGFBP-3-PA in both groups (P < 0.005), whereas no significant responses could be
      demonstrated during the pre-op clamp. The expression of increased IGFBP-3-PA was
      accompanied by conversion of endogenous intact 39/42-kDa IGFBP-3 into its 30-kDa
      fragmented form as determined by Western immunoblotting, and this conversion was
      virtually complete after the 4-h post-op clamp in patients displaying marked
      increases in IGFBP-3-PA. Characterization of the IGFBP-3-PA demonstrated that it
      was specific for IGFBP-3, as no degradation of IGFBP-1 and -2 was detected, and
      the use of various protease inhibitors demonstrated that serine proteases and
      possibly matrix metalloproteinases contribute to the increased IGFBP-3-PA level
      after surgery. We propose that IGF bioavailability may be increased by the
      induction of IGFBP-3-PA in insulin-resistant subjects, and that insulin regulates
      IGFBP-3-PA in this state.

PMID- 9661637
TI  - Effects of p53-expressing adenovirus on the chemosensitivity and differentiation
      of anaplastic thyroid cancer cells.
AB  - We investigated the p53 status and the ability of exogenous wildtype (wt) p53 to
      affect chemosensitivity in three anaplastic thyroid carcinoma cell lines (BHT
      101, SW-1736, and KAT-4). All three cell lines had nonfunctional p53. Treatment
      with mitomycin C or adriamycin did not result in accumulation of p53 or induction
      of p21WAF1/CIP1 or Mdm-2 and did not cause Rb dephosphorylation. BHT-101 and KAT
      4 cells had mutant p53. SW-1736 cells were functionally mutant because of marked
      down-regulation of wt p53 messenger ribonucleic acid, representing a novel
      mechanism of p53 dysfunction. Infection with a p53-expressing adenovirus (Ad-p53)
      induced high levels of p21 and Mdm-2 proteins. In BHT-101 cells, induction of p21
      and Mdm-2 was evident 10 h after infection. In KAT-4 cells, induction of p21 and
      Mdm-2 was observed 1 day after infection, and continued to increase over the
      ensuing 24 h. SW-1736 cells demonstrated intermediate kinetics. Sensitivity to
      the cytotoxic effect of Ad-p53 paralleled the kinetics of p21/Mdm-2 induction.
      BHT-101 cells were most sensitive to killing by Ad-p53, with an IC50 of less than
      2 multiplicity of infection; SW-1736 cells were intermediate in sensitivity; KAT
      4 cells were resistant. All three cell lines became more sensitive to adriamycin
      after wt p53 expression, with a 10-fold decrease in IC50 values. The latter
      observation may make a combination of wt p53 and chemotherapeutic drugs an
      attractive modality for treating anaplastic thyroid cancer.

PMID- 9661638
TI  - N-acetyl-L-cysteine inhibits apoptosis in human male germ cells in vitro.
AB  - Antioxidant defenses play a critical role in the regulation of programmed cell
      death, even when death is induced by nonoxidative stimuli. During
      spermatogenesis, most of the testicular germ cells degenerate by an apoptotic
      process that is under hormonal control. However, the exact mechanisms by which
      hormonal signals are transduced within the cells to direct their life, and
      whether other effectors of the apoptotic pathway, for example antioxidants, take
      part in the control of human germ cell survival, are not known. In the present
      study, testosterone and N-acetyl-L-cysteine (NAC), which is an antioxidant, an
      inhibitor of apoptosis in several systems, and a survival factor in human semen,
      were found to suppress programmed cell death in human testicular germ cells in
      vitro. The samples came from adult men undergoing orchidectomy for prostate
      cancer. Germ cell death was induced by incubating segments of seminiferous
      tubules under serum-free culture conditions. This apoptosis, detected by Southern
      blot analysis of DNA fragmentation, by DNA labeling in situ, and by morphological
      analysis under the electron microscope, was significantly inhibited by
      testosterone at concentrations of 10(-6) and 10(-7) mol/L. NAC concentrations of
      125, 100, 50, and 25 mmol/L suppressed germ cell death in a dose-dependent
      manner. This inhibition was effective during 4, 24, and 48 h of incubation.
      Apoptotic cells were identified mainly as spermatocytes and early spermatids.
      Programmed cell death was also demonstrated in late spermatids. We conclude that
      NAC, which is an antioxidant, plays an important role in germ cell survival in
      the human seminiferous tubules in vitro. We also suggest NAC as a possible new
      therapeutic factor for some men with idiopathic oligospermia.

PMID- 9661639
TI  - Cirrhotic liver expresses low levels of the full-length and truncated growth
      hormone receptors.
AB  - In cirrhosis, as in other conditions of protein catabolism, there is a state of
      acquired GH resistance, as defined by high circulating GH levels with low insulin
      like growth factor I levels. However, patients with end-stage liver failure
      respond to supraphysiological doses of GH with an increase in circulating insulin
      like growth factor I levels. The present study represents a detailed analysis of
      GH receptor (GHR) expression in cirrhotic liver from 17 patients with end-stage
      liver disease. Specific binding of labeled GH was identified in all cirrhotic
      livers studied. The binding affinity for the GHR was similar in cirrhotic and
      normal livers, but the number of binding sites per mg protein of liver membrane
      was variable in both normal and cirrhotic liver, although it were generally lower
      in cirrhotic liver. GHR expression was identified in cirrhotic liver by Northern
      blotting, RT-PCR, and ribonuclease protection assay. On Northern blotting, a
      single transcript of 4.8 kb was identified in normal and cirrhotic tissues. RT
      PCR identified expression of both full-length GHR and a truncated form of the
      GHR; this was confirmed by ribonuclease protection assay. In situ hybridization
      and immunohistochemistry confirmed the expression of GHR in regenerating
      hepatocytes and isolated cells in fibrous tissue. In conclusion, 1) the low level
      of GHR in cirrhotic liver may contribute to the acquired GH resistance found in
      cirrhotic patients; 2) the reduced expression of both full-length and truncated
      GHR is compatible with the low level of GH-binding protein found in cirrhosis, as
      this truncated receptor has previously been reported to generate large amounts of
      GH-binding protein; and 3) the demonstration of GH binding to cirrhotic liver
      explains why these patients with GH resistance may still respond to
      supraphysiological doses of GH.

PMID- 9661640
TI  - Human corticotropin-releasing hormone receptor: differences in subtype expression
      between pregnant and nonpregnant myometria.
AB  - There is increasing evidence that CRH, which is the principal neuroregulator of
      the hypothalamic-pituitary-adrenocortical axis, is also involved in the mechanism
      of human labor. The human myometrium has been shown to express several high
      affinity CRH receptors, although the identities of the CRH receptor subtypes have
      yet to be identified. To investigate further the expression of the CRH receptor
      in human myometrium, we used RT-PCR, fluorescent in situ hybridization and
      immunofluorescence to identify and localize the four subtypes, 1 alpha, 1 beta, 2
      alpha, and the variant C, of the CRH receptor. Interestingly, the CRH receptor
      subtypes in myometrium exhibit differential expression patterns; in human
      pregnant myometrium at term all four receptor-subtypes were expressed, whereas
      only the 1 alpha- and 1 beta-receptor subtypes were found in the nonpregnant
      myometrium. This would suggest that CRH, acting via different receptor subtypes,
      is able to exert different actions on the myometrium in the pregnant state
      compared to the nonpregnant state. Furthermore, in the pregnant human uterus, CRH
      receptors were localized in both smooth muscle and fibroblasts. These findings
      suggest that CRH receptor expression plays an important modulatory role in
      myometrial and possibly in cervical function.

PMID- 9661641
TI  - Expression of functional prolactin receptors in nonpregnant human endometrium:
      janus kinase-2, signal transducer and activator of transcription-1 (STAT1), and
      STAT5 proteins are phosphorylated after stimulation with prolactin.
AB  - PRL is synthesized by decidualized endometrial stromal cells from the
      midsecretory phase in a nonconception cycle and throughout pregnancy. The exact
      role of PRL in the human endometrium remains to be elucidated; however, the
      pattern of expression supports a role for PRL during implantation and
      placentation. This study investigated the site and pattern of expression of PRL
      receptors in the nonpregnant human endometrium. In situ hybridization and
      immunohistochemistry localized expression of the receptor in the glandular
      epithelium and a subset of stromal cells of the endometrium. As judged by the
      intensity of staining, expression of the receptor was dramatically up-regulated
      during the secretory phase. Expression of the PRL receptor gene in the
      endometrium from the secretory phase of the menstrual cycle was confirmed by
      ribonuclease protection assay using 50 micrograms total ribonucleic acid.
      Phosphorylation of Janus kinase-2 (JAK2), STAT1 (signal transducer and activator
      of transcription-1), and STAT5 proteins in response to PRL was investigated to
      establish the signaling pathway of PRL in the human endometrium. Endometrial
      tissue was collected during the secretory phase of the menstrual cycle and
      incubated in the presence of 100 ng/mL human PRL for 0, 5, 10, and 20 min. JAK2
      phosphorylation was induced by PRL at 5 min, whereas STAT1 and STAT5
      phosphorylation was apparent 20 min after stimulation with PRL.
      Immunohistochemistry localized the JAK/STAT proteins in the glandular epithelial
      cells and a subset of stromal cells, as was observed for the PRL receptor.
      Secretory phase stromal and glandular cells cultured separately and in the
      presence or absence of 100 ng/mL PRL confirmed the PRL-induced phosphorylation of
      JAK2/STAT proteins, at least in the glandular compartment. These studies
      demonstrate an up-regulation of expression of functional PRL receptors during the
      secretory phase of the menstrual cycle. Further, decidual PRL through a paracrine
      mechanism may influence glandular epithelial function/secretions and direct gene
      transcription through the JAK/STAT pathway. The target genes activated by PRL in
      the glandular epithelium of the nonpregnant human endometrium remain to be
      elucidated.

PMID- 9661642
TI  - A novel mutation affecting the interdomain link region of the growth hormone
      receptor in a Vietnamese girl, and response to long-term treatment with
      recombinant human insulin-like growth factor-I and luteinizing hormone-releasing
      hormone analogue.
AB  - A Vietnamese girl with Laron syndrome has been treated with recombinant human
      insulin-like growth factor-I for 4 yr from age 11.28 yr. Her height SD score
      increased from -6.3 to -4.7 without acceleration of bone age. Isolated breast
      development progressed despite pubertal suppression with luteinizing hormone
      releasing hormone analogue, which was stopped after 3 yr because of growth
      deceleration. Facial coarsening was documented with serial photographs.
      Sequencing and in vitro analysis identified a homozygous base pair substitution
      in exon 6 of the proband's GH receptor (GHR), which changed amino acid 131 from
      proline to glutamine (P131Q) and disrupted GH binding. Both the P131Q-mutated
      human GHR and wildtype (wt) hGHR were transiently expressed in COS-1 cells, as
      demonstrated by Western blotting, but the P131Q-transfected cells did not bind
      125I-hGH. Similarly, FDC-P1 cells transfected with wthGHR bound 125I-hGH with
      high affinity and proliferated in response to GH, whereas the P131Q hGHR cells
      did neither. In CHO-K1 cells cotransfected with wthGHR and the Egr-1 promotor
      linked to a luciferase reporter gene, GH evoked a 2.14 +/- 0.21-fold increase in
      luciferase activity, but there was no response in the cells carrying the P131Q
      hGHR mutation. From examination of the crystal structure of the GHR, we suggest
      that the P131Q mutation disrupts the interdomain link between the extracellular
      domains of the GHR, causing a conformational change that results in disruption of
      the GH binding site.

PMID- 9661643
TI  - Urinary growth hormone (GH), insulin-like growth factor I (IGF-I), and IGF
      binding protein-3 measurements in the diagnosis of adult GH deficiency.
AB  - The diagnosis of GH deficiency (GHD) in the elderly is based at present on the
      peak GH concentration during a stimulation test. We have now evaluated the
      performance of urinary GH (uGH), urinary insulin-like growth factor I (uIGF-I),
      and urinary IGF-binding protein-3 (uIGFBP-3) in the diagnosis of GHD in this
      group. Twenty GHD elderly patients with a history of pituitary disease and a peak
      GH response to arginine stimulation of less than 3 ng/mL (15 men and 5 women;
      age, 61.1-83.4 yr) and 19 controls (12 men and 7 women; age, 60.8-87.5 yr) were
      studied. GH secretion was assessed by 24-h profile and expressed as the area
      under the curve (AUCGH). Serum (s) IGF-I and sIGFBP-3 were measured in a single
      morning, fasted sample. Urinary GH, uIGF-I, and uIGFBP-3 were measured in a 24-h
      urine sample collected over the same interval as the GH profile, and results were
      expressed as total amount excreted in 24 h (tuGH24, nanograms; tuIGF-I24,
      nanograms; tuIGFBP-3(24), micrograms). Data are presented as the mean +/- SD,
      except for AUCGH, tuGH24, and tuIGFBP-3(24), which are presented as the geometric
      mean (-1, +1 tolerance factor). AUCGH, sIGF-I, and sIGFBP-3 were significantly
      lower in GHD subjects than in controls. Total uGH24 was lower in GHD subjects,
      but tuIGF-I24 and tuIGFBP-3(24) excretion were not different in the two groups.
      AUCGH provided the best separation between GHD and control subjects, whereas
      there was substantial overlap for sIGF-I, sIGFBP-3, and tuGH24. In both groups
      sIGF-I was correlated to sIGFBP-3 (GHD, r = 0.75; controls, r = 0.65; both P <
      0.01), whereas tuIGF-I24 was not correlated to tuIGFBP-3(24) in either group.
      Moreover, tuIGF-I24 and tuIGFBP-3(24) were not related to their respective serum
      concentrations in either group. Total uGH24 was correlated with AUCGH only in
      controls (r = 0.54; P < 0.05). These data demonstrate that urinary GH and urinary
      and serum IGF-I and IGFBP-3 are not suitable diagnostic markers for GHD in
      elderly subjects.

PMID- 9661644
TI  - Decreased serum leptin concentrations during metformin therapy in obese women
      with polycystic ovary syndrome.
AB  - Previous studies have suggested that metformin is clinically useful in the
      treatment of polycystic ovary syndrome (PCOS). The aim of this study was to
      evaluate whether the improvement of ovarian function achieved by metformin
      therapy is associated with changes in leptin concentrations. Twenty-six obese
      women with PCOS were treated with 500 mg metformin, x 3 daily, for 2 months; and
      12 women continued the therapy for 4-6 months. A significant decrease in the
      serum leptin level was observed after 2 months of treatment in the whole study
      group (29.2 +/- 12.7 ng/mL vs. 25.7 +/- 10.9 ng/mL, P = 0.03). In the 12 women
      treated for 4-6 months, the mean serum leptin concentration decreased after 2
      months (38.6 +/- 9.3 ng/mL vs. 30.2 +/- 8.1 ng/mL; P = 0.004) but slightly
      increased after 4-6 months of treatment (33.4 +/- 15.7 ng/mL; not significant).
      These results indicate that insulin sensitizing therapy with metformin decreases
      the leptin concentrations in obese PCOS women.

PMID- 9661645
TI  - Preserved growth hormone (GH) secretion in aged and very old subjects after
      testing with the combined stimulus GH-releasing hormone plus GH-releasing
      hexapeptide-6.
AB  - Either spontaneous or pharmacological stimulated GH secretion is reduced with
      advanced age. This observation is an added difficulty for the biochemical
      diagnosis of GH deficiency in adults. Furthermore, the combined administration of
      saturating doses of GH-releasing hormone (GHRH) plus GH-releasing hexapeptide
      (GHRP)-6 is nowadays the most effective GH-releasing stimulus tested in a variety
      of settings related to altered somatotroph function. To understand whether the GH
      discharge elicited by the combined stimulus declines with age, 26 normal subjects
      of both sexes, divided into 3 age groups [adults 19-40 yr; aged 46-65 yr; and
      very old (75-96 yr) subjects] were studied. They were administered i.v., as bolus
      and in combination, 90 micrograms GHRH plus 90 micrograms GHRP-6. In the three
      groups, the combined administration of GHRH plus GHRP-6 elicited a GH area under
      the curve (microgram/L per 120 min) of 3,127 +/- 262, 3,409 +/- 573, and 4,655 +/
      737 for adults, aged, and very old subjects, respectively (nonsignificant
      differences). The mean GH peak was 47.5 +/- 4.5 micrograms/L for adults, 52.9 +/-
      8.4 micrograms/L for aged subjects, and 76.0 +/- 11.7 for very old subjects
      (nonsignificant differences). Individually examined, there were no nonresponders
      to the combined stimulus, and all subjects (independently of age) showed a GH
      peak over 25 micrograms/L (the lowest peak was 27.3 micrograms/L, and the highest
      peak was 119.2 micrograms/L). In conclusion, the GHRH plus GHRP-6-induced GH
      release is well preserved in aged and very old subjects, which suggests that the
      GH secretory capability of the combined test is not reduced by age. This combined
      test may be useful for the diagnosis of GH-deficient states in adults.

PMID- 9661646
TI  - Diagnosis of glucocorticoid-remediable aldosteronism in primary aldosteronism:
      aldosterone response to dexamethasone and long polymerase chain reaction for
      chimeric gene.
AB  - Aldosterone suppression by dexamethasone, and high 18-hydroxycortisol and 18
      oxocortisol levels are used to differentiate glucocorticoid-remediable
      aldosteronism (GRA) from other forms of primary aldosteronism. These methods are
      time consuming, expensive, and impractical for large studies. Moreover, diagnosis
      of GRA requires a confirmatory genetic test. We evaluated 117 patients with
      primary aldosteronism referred to our centers by the use of a long PCR technique
      to reveal the chimeric gene of GRA. In 60 of 117 patients, the response of
      aldosterone to dexamethasone (2 mg/day for 4 days) was also assessed. None of our
      patients, including 2 pairs of siblings, was positive for the chimeric gene. The
      results of long PCR were confirmed by Southern blotting. Despite a negative
      genetic test, 6 patients (1 with aldosterone-producing adenoma and 5 with
      idiopathic hyperaldosteronism) had plasma aldosterone suppressed by dexamethasone
      (i.e. < or = 2 ng/dL). Of 117 patients, 43 were identified as having aldosterone
      producing adenoma and 74 as having idiopathic hyperaldosteronism. In our
      experience, the long PCR technique is a reliable and simple test to at least
      exclude GRA in patients with primary aldosteronism. A short term dexamethasone
      suppression test of aldosterone can be misleading in identifying GRA. The
      prevalence of GRA in primary aldosteronism remains to be established.

PMID- 9661647
TI  - Normal growth hormone secretory reserve in men with idiopathic osteoporosis and
      reduced circulating levels of insulin-like growth factor-I.
AB  - Many men with idiopathic osteoporosis have reduced circulating insulin-like
      growth factor-I (IGF-I) levels. The major source of circulating IGF-I is GH
      mediated production by the liver. The known anabolic effects of GH on the
      skeleton raised the possibility of GH deficiency in these men. We sought to test
      this hypothesis in this study. Fourteen men (mean age, 52.1 +/- 3.2 yr, range 31
      68) with idiopathic osteoporosis were studied. Mean lumbar spine bone mineral
      density (BMD) was 0.723 g/cm2, T score -3.5; femoral neck BMD was 0.642 g/cm2, T
      score, -3.07; distal (1/3) radius BMD was 0.708 g/cm2, T score, -2.05. Eleven of
      14 (79%) had frank reductions in serum IGF-I levels compared with age and sex
      matched values (158.5 +/- 50 SD vs. 180 +/- 45 SD). GH secretion was stimulated
      by iv arginine infusion (30 g) over 30 min followed 1 h later by oral L-dopa (500
      mg). Serum GH was measured at time (t) = -15, 0, 30, 45, 60, 90, 120, 150, and
      180 min. All patients responded to at least one stimulus with the majority (n =
      9) responding to both. Five patients responded either to arginine or to L-dopa
      but not to both. Baseline GH for the entire group was 0.77 + 0.08 ng/mL (SEM).
      Peak GH following arginine (t = 45-60 min) was 14.0 +/- 2.8 ng/mL, a 17.7 +/- 2.8
      fold rise. Peak GH following L-dopa (t = 120-180 min) was 5.7 +/- 1.0 ng/mL, a
      9.2 +/- 2.2-fold rise. No difference in maximal secretion was observed between
      those with low or normal IGF-I levels. Neither IGF-I nor IGF binding protein-3
      concentrations changed significantly during the short period of GH stimulation.
      These data suggest that men with osteoporosis and reduced IGF-I levels do not
      appear to have a deficiency in the GH axis. Other hormonal or local factors may
      be important in regulating IGF-I expression. Deficiencies of IGF-I production at
      skeletal sites may be important in the pathogenesis of this syndrome.

PMID- 9661648
TI  - The increased circulating prostate-specific antigen concentrations in women with
      hirsutism do not respond to acute changes in adrenal or ovarian function.
AB  - Serum prostate-specific antigen (PSA) is produced in several female tissues and
      appears to be up-regulated by androgens. We have studied serum PSA concentrations
      in women with different forms of hyperandrogenism, focusing on the influence of
      changes in ovarian and adrenal function on these concentrations. Thirty-seven
      hirsute women were studied in the follicular phase of the menstrual cycle. Basal
      and ACTH-stimulated plasma samples were obtained, and sampling was repeated 1
      (gonadal stimulation) and 21 (gonadal suppression) days after receiving a single
      im 3.75-mg dose of triptorelin. Eleven nonhyperandrogenic women served as
      controls. Hirsute women had increased PSA levels compared to controls. When
      considering the source of the hyperandrogenism, ovarian patients (those with
      increased serum androgen levels that normalized during gonadal suppression) and
      adrenal patients (those with increased androgen levels that remained elevated
      during gonadal suppression) presented increased PSA values, whereas hirsute
      patients without hyperandrogenemia had normal PSA levels. PSA levels did not
      change during ovarian or adrenal stimulation or during gonadal suppression with
      respect to initial values. Basal PSA levels showed significant correlations with
      basal total testosterone (r = 0.59; P < 0.001), free androgen index (r = 0.68; P
      < 0.001), sex hormone-binding globulin (r = -0.58; P < 0.001),
      dehydroepiandrosterone sulfate (r = 0.39; P < 0.01), 17-hydroxyprogesterone (r =
      0.32; P < 0.05), and age (r = -0.33; P < 0.05) when patients and controls were
      considered as a whole. In conclusion, basal PSA levels are increased in hirsute
      patients and correlate with the degree of hyperandrogenism when patients and
      controls are considered as a whole. The adrenal and the ovary do not appear to be
      the source of PSA, suggesting that hyperandrogenism induces PSA secretion in
      tissues other than the adrenal and the ovary.

PMID- 9661649
TI  - Steroid 21-hydroxylase mutations and 21-hydroxylase messenger ribonucleic acid
      expression in human adrenocortical tumors.
AB  - Twenty-one hydroxylase (P450c21) is a key enzyme essential for normal zona
      glomerulosa and fasciculata function. Recently, 21-hydroxylase deficiency has
      been implicated in the pathogenesis of adrenocortical tumors. Therefore, we
      investigated the mutational spectrum of the CYP21B gene and the messenger RNA
      expression of P450c21 in six aldosterone-producing adenomas, seven cortisol
      producing adenomas, two nonfunctional incidentally detected adenomas, and four
      adrenal carcinomas. DNA from leukocytes and tumors was amplified by PCR using
      primers specific for the CYP21B gene. The 10 exons, intron 2, intron 7, all other
      exon/intron junctions, and 380 bp of the promoter region of CYP21B were
      automatically sequenced. Poly(A) RNA was extracted from tumor tissue, dot blotted
      on a nylon membrane, and hybridized with 32P-labeled P450 side-chain cleavage,
      P450 17-alpha-hydroxylase, and P450c21 complementary DNA probes. We detected
      heterozygous germline mutations (exon 7, Val 281Leu) in two patients, one with a
      cortisol-producing adenoma and the other with an androgen-secreting
      adrenocortical carcinoma. A somatic, heterozygous microdeletion was found in exon
      3 of one aldosterone-producing adenoma. The P450c21 gene expression correlated
      with the clinical phenotype of the tumor, with low P450c21 messenger RNA
      expression in nonfunctional adenomas (18.8%, 1.5%) compared with high P450c21
      expression in aldosterone- and cortisol-producing adenomas (84 +/- 8% and 101 +/-
      4%, respectively, vs. normal adrenals, 100 +/- 10%). In conclusion, the
      prevalence of heterozygous germline mutations in the CYP21B gene was higher in
      patients with adrenocortical tumors (11%; 95% confidence interval, 1-34%) than in
      the general European population (2%; 95% confidence interval, 1.93-2.06%), but
      this difference is questionable because of the low number of subjects in our
      series. The pathophysiological significance of this finding in the presence of
      one normal CYP21B gene seems to be low, suggesting that 21-hydroxylase deficiency
      is not a major predisposing factor for adrenal tumor formation.

PMID- 9661650
TI  - A variant of paraoxonase (PON1) gene is associated with diabetic retinopathy in
      IDDM.
AB  - Serum paraoxonase is a glycoprotein which binds to high-density lipoproteins
      (HDL) and may prevent oxidation of LDL by hydrolyzing lipid peroxides. Two
      polymorphisms identified in the paraoxonase gene (Met-Leu 54 and Gln-Arg 192)
      have been associated with cardiovascular disease. Oxidative low-density
      lipoprotein (LDL) is also toxic to retinal capillary endothelial cells and
      pericytes, so that mildly modified LDL may contribute to the development of
      diabetic retinopathy. To investigate the potential significance of these
      polymorphisms in the pathogenesis of diabetic retinopathy in IDDM, 80 patients
      with diabetic retinopathy and 119 controls without diabetic retinopathy were
      investigated in the current project. The allelic frequency of leucine 54 (L) was
      significantly higher in the group with retinopathy than without retinopathy (73%
      vs. 57%, p < 0.001). The genotype L/L was strongly associated with the
      development of diabetic retinopathy (p < 0.001), but a similar association was
      not found with Gln-Arg 192. Leucine 54 is a risk factor for diabetic retinopathy.

PMID- 9661651
TI  - Identification of glycosylated 38-kDa connective tissue growth factor (IGFBP
      related protein 2) and proteolytic fragments in human biological fluids, and up
      regulation of IGFBP-rP2 expression by TGF-beta in Hs578T human breast cancer
      cells.
AB  - Connective Tissue Growth Factor (CTGF) is a cysteine-rich peptide involved in
      human atherosclerosis and fibrotic disorders such as scleroderma. CTGF has
      considerable N-terminal sequence similarity with the insulin-like growth factor
      binding proteins (IGFBPs), including preservation of cysteines, and has been
      postulated to be a member of the IGFBP superfamily. Indeed, recent studies have
      shown that baculovirus generated CTGF, a secreted 38-kDa protein, binds IGFs in a
      specific manner, leading to the provisional renaming of CTGF as IGFBP-8 (or IGFBP
      rP2). With immunoprecipitation and immunoblotting, using polyclonal anti-IGFBP
      rP2 antibody generated against recombinant human IGFBP-rP2bac, IGFBP-rP2 can be
      identified in the serum-free conditioned media of Hs578T human breast cancer
      cells, as well as in various human biological fluids, such as normal sera,
      pregnancy sera, and cerebrospinal, amniotic, follicular and peritoneal fluids.
      Glycosylation studies with endoglycosidase F reveal that endogenous human IGFBP
      rP2 is a secreted, glycosylated, approximately 32-38-kDa protein with 2-8-kDa of
      N-linked sugars and a 30-kDa core. There are 18- and 24-kDa proteins that appear
      to be IGFBP-rP2 degradation products. In Hs578T human breast cancer cells,
      transforming growth factor (TGF)-beta 2, a potent growth inhibitor for these
      cells, upregulates IGFBP-rP2 mRNA and protein levels. Expression of Hs578T IGFBP
      rP2 is significantly increased by TGF-beta 2 treatment in a dose-dependent
      manner, with 2.5- and 6-fold increases in mRNA and protein levels, respectively,
      at a TGF-beta 2 concentration of 10 ng/ml. Our studies indicate that IGFBP-rP2
      appears to be an important endocrine factor, and one of the critical downstream
      effectors of the critical downstream effectors of TGF-beta, similar to the role
      of IGFBP-3 in TGF-beta-induced growth inhibition in human breast cancer cells.

PMID- 9661652
TI  - DAX-1 expression in human adrenocortical neoplasms: implications for
      steroidogenesis.
AB  - The DAX-1 gene encodes an orphan nuclear hormone receptor essential for normal
      fetal development of the adrenal cortex. Recently, DAX-1 has been shown to act as
      a transcriptional repressor of steroidogenic acute regulatory protein gene
      expression (StAR), suppressing steroidogenesis. We, therefore, investigated the
      expression of DAX-1 in a variety of adrenocortical tumors and compared the
      results with StAR mRNA expression. We found low or absent DAX-1 expression in
      aldosterone-producing adenomas (n = 11: 35 +/- 11%; normal adrenals: 100 +/- 17%)
      and in aldosterone-producing adrenocortical carcinomas (n = 2: 24 and 36%).
      Cortisol-producing adenomas showed intermediate DAX-1 expression (n = 8; 92 +/-
      16), as did 3 non-aldosterone-producing carcinomas (72, 132 and 132%). High DAX-1
      expression was present in nonfunctional adenomas (n = 3; 160 +/- 17%). In
      contrast to DAX-1, StAR mRNA expression did not show significant variations
      between groups. We did not detect the expected negative correlation between DAX-1
      and StAR in adrenocortical tumors. These data suggest that high DAX-1 expression
      in adrenocortical tumors is associated with a non-functional phenotype whereas
      low DAX-1 expression favors mineralocorticoid secretion. These effects on
      steroidogenesis are mediated by mechanisms other than repression of StAR gene
      expression. Our results indicate that DAX-1 may be one of the factors influencing
      the steroid biosynthesis of adrenocortical neoplasms.

PMID- 9661653
TI  - Compound heterozygous deletion of the PROP-1 gene in children with combined
      pituitary hormone deficiency.
AB  - Mutations in the prophet of Pit-1 gene (PROP1) have been shown to be responsible
      for combined pituitary hormone deficiency (CPHD) with deficiencies of growth
      hormone (GH), Prolactin (Prl), thyroid-stimulating hormone (TSH) and
      gonadotropins. We previously reported that homozygosity for a 2bp deletion in
      exon 2 (296delGA) accounted for CPHD in three patients from two Russian families.
      Here we report a second mutational hot spot in exon 2. This 2bp 149delGA deletion
      results in a frame shift that leads to the same serine to stop codon change at
      codon 109 (S109X). The predicted proteins are each truncated at residue 108 but
      diverge from the wild type sequence at different points in the homeodomain.
      Compound heterozygosity for the two mutations (149delGA/296delGA) was detected in
      5 of 14 CPHD children from 4 families (36%). This provides the first evidence of
      heterozygosity for two common deletions as a cause of CPHD in Russian children.

PMID- 9661654
TI  - Bone and collagen turnover in patients with active and preclinical Cushing's
      syndrome and in subjects with adrenal incidentaloma.

PMID- 9661655
TI  - Comment on prostatic hyperplasia in patients with acromegaly.

PMID- 9661656
TI  - Concerning minimal cardiac effects in asymptomatic athyreotic patients treated
      with thyrotropin-suppressive doses of L-thyroxine.

PMID- 9661657
TI  - Variation in the proregion structure of heparin-binding EGF-like growth factor
      precursors.
AB  - In a previous study, we have isolated and characterized cDNA encoding a novel
      'short form' of heparin-binding EGF-like growth factor (SF HB-EGF) (Loukianov et
      al., 1997). In the present work, we have found that cDNA for SF HB-EGF and for
      full-length HB-EGF are each represented by two variants, which we refer to as L
      and P forms. The L form is the previously known form of HB-EGF cDNA and encodes a
      leucine in position 33. The P form described in this report, encodes a proline in
      codon 33. The L33P substitution is predicted to cause a significant alteration in
      the proregion structure of SF HB-EGF and HB-EGF.

PMID- 9661658
TI  - A leucine repeat motif in AbiA is required for resistance of Lactococcus lactis
      to phages representing three species.
AB  - The abiA gene encodes an abortive bacteriophage infection mechanism that can
      protect Lactococcus species from infection by a variety of bacteriophages
      including three unrelated phage species. Five heptad leucine repeats suggestive
      of a leucine zipper motif were identified between residues 232 and 266 in the
      predicted amino acid sequence of the AbiA protein. The biological role of
      residues in the repeats was investigated by incorporating amino acid
      substitutions via site-directed mutagenesis. Each mutant was tested for phage
      resistance against three phages, phi 31, sk1, and c2, belonging to species P335,
      936, and c2, respectively. The five residues that comprise the heptad repeats
      were designated L234, L242, A249, L256, and L263. Three single conservative
      mutations of leucine to valine in positions L235, L242, and L263 and a double
      mutation of two leucines (L235 and L242) to valines did not affect AbiA activity
      on any phages tested. Non-conservative single substitutions of charged amino
      acids for three of the leucines (L235, L242, and L256) virtually eliminated AbiA
      activity on all phages tested. Substitution of the alanine residue in the third
      repeat (A249) with a charged residue did not affect AbiA activity. Replacement of
      L242 with an alanine elimination phage resistance against phi 31, but partial
      resistance to sk1 and c2 remained. Two single proline substitutions for leucines
      L242 and L263 virtually eliminated AbiA activity against all phages, indicating
      that the predicted alpha-helical structure of this region is important. Mutations
      in an adjacent region of basic amino acids had various effects on phage
      resistance, suggesting that these basic residues are also important for AbiA
      activity. This directed mutagenesis analysis of AbiA indicated that the leucine
      repeat structure is essential for conferring phage resistance against three
      species of lactococcal bacteriophages.

PMID- 9661659
TI  - Characterization of the human NIPSNAP1 gene from 22q12: a member of a novel gene
      family.
AB  - Rapid progress in sequencing of human and other genomes allows high-resolution
      analysis of their gene content on the basis of comparison between species. We
      have used a combined computer and biochemical approach to characterize 135 kb of
      human genomic sequence from 22q12 and discovered a new 10 exon gene, termed
      NIPSNAP1, located between the neurofibromatosis type 2 and the pK1.3 genes. The
      NIPSNAP1 gene spans 26 kb of genomic sequence and shows to large introns in the
      5'-region. All exon-intron junctions contain the gt/ag consensus splice site. The
      putative promoter of the NIPSNAP1 gene is TATA-less and resides in a GC-rich
      island characteristic of housekeeping genes. The NIPSNAP1 mRNA is 2.1 kb, is
      expressed ubiquitously at variable levels, with the highest expression in liver,
      is terminated by an uncommon ATTAAA polyadenylation site, and is capable of
      encoding a 284-amino-acid protein. This NIPSNAP1 protein has a strong sequence
      similarity limited to the central portion of a hypothetical protein (acc. P34492)
      from chromosome III of C. elegans, in which the other portions resemble a 4
      nitrophenylphosphatase domain and non-neuronal SNAP25-like protein. Thus, the
      NIPSNAP1 gene is a member of an evolutionarily well conserved, novel gene family
      with two members in human and mouse that have now been characterized, and one
      member in C. elegans. The second human gene, NIPSNAP2, is localized in the
      vicinity of marker D7S499 on chromosome 7. Although the function of the NIPSNAP
      protein family is unknown, clues about its role may reside in the co-expression
      of the C. elegans orthologue, within an operon encoding protein motifs known to
      be involved in vesicular transport.

PMID- 9661660
TI  - Host vector system for high-level expression and purification of recombinant,
      enzymatically active alanine dehydrogenase of Mycobacterium tuberculosis.
AB  - The 40-kDa antigen of M. tuberculosis, which is an alanine dehydrogenase, is a
      species-specific antigen that is potentially useful for strain identification.
      Large quantities of the purified protein are required for immunological, as well
      as for detailed biochemical and structural, characterization. The AlaDH gene was
      cloned by PCR from H37Rv (virulent) and H37Ra (partially attenuated) strains of
      M. tuberculosis, and their DNA sequence was determined. A host-vector system
      suitable for the production of sufficient quantities of the recombinant AlaDH
      antigen was developed. The AlaDH gene was expressed under the control of strong,
      transcriptional (bacteriophage pLpR) and translational (atpE) signals. High-level
      expression of soluble AlaDH was obtained using the recombinant E. coli K-12
      strain CAG629 [pMSK12], which is deficient in Lon protease and the heat-shock
      response. A simple two-step procedure for the rapid purification of the
      recombinant protein was developed. The protein was purified to near homogeneity,
      and the purified AlaDH showed a specific enzyme activity comparable to the native
      protein isolated from M. tuberculosis. In addition, the product showed an
      expected amino acid sequence and reacted strongly to the 40-kDa (AlaDH)-specific
      mAb HBT-10. Furthermore, the epitope of the mAb HBT-10 was mapped to a 12-amino
      acid region. Contrary to the published results, we show that the AlaDH and the
      PNT (pyridine nucleotide transhydrogenase) of M. tuberculosis do not share common
      epitopes reacting to the species-specific mAb HBT-10. The availability of highly
      purified AlaDH should now enable a detailed biochemical and structural
      characterization of this important enzyme of M. tuberculosis.

PMID- 9661661
TI  - Cloning and comparative sequence analysis of TP53 in Xiphophorus fish hybrid
      melanoma models.
AB  - We have cloned and sequenced the p53-encoding cDNA of green swordtail (X.
      helleri) and southern platyfish (X. maculatus). These two fish species are often
      used to produce hybrids that develop melanomas after genetic crossing. Computer
      translation of derived cDNA sequences revealed that p53 polypeptides from these
      two species are virtually identical, exhibiting only two conservative amino acid
      substitutions. TP53 mRNA expression was detected in virtually all tissues tested.
      Comparison of these fish p53 polypeptide sequences with those of other
      vertebrates, including other fishes, amphibians, and mammals, revealed that
      conservation is especially high in several previously defined protein domains. In
      addition, sequencing of the 3' TP53 genomic region of X. maculatus reveals
      similarity to the human TP53 locus in overall organization. Knowledge of the
      Xiphophorus TP53 sequences will allow assessment of mutational alterations within
      tumors generated from numerous fish genetic crosses.

PMID- 9661662
TI  - A novel isoform of human membrane cofactor protein (CD46) mRNA generated by
      intron retention.
AB  - The reverse transcription polymerase chain reaction (RT-PCR) with primers
      specific for each of the 14 exons of the human complement regulatory protein
      membrane cofactor protein (MCP;CD46) has been utilized to determine MCP mRNA
      transcript expression in peripheral blood mononuclear cells (PBMC). An additional
      transcript of a larger size than predicted was consistently detected in reactions
      with a sense primer for exon 7, that encodes the first alternatively spliced
      serine-threonine-rich region (ST-A), together with an antisense exon 12 primer,
      RT-PCR with primers for other exons both 5' and 3' of exon 7 further showed that
      these MCP transcripts contain additional sequences immediately both 5' and 3' to
      the exon 7-encoded sequence. Comparison of genomic DNA with cDNA by PCR, in
      combination with sequence analysis, demonstrated the presence of the complete
      invariant sequences of both introns adjacent to exon 7, i.e. intron 6 (411 bp)
      and intron 7 (127 bp). RT-PCR using primers specific for the intron 6 sequence,
      together with Southern and Northern blotting using an intron 6-specific probe,
      confirmed retention of this intron within a novel 4.8-kb mRNA transcript in human
      PBMC. Due to the presence of a stop codon within intron 6, translation would
      result in a novel truncated MCP isoform (MCPi) containing the four invariant
      short consensus repeat (SCR) regions and a unique C-terminal 39 amino acid
      transmembrane and cytoplasmic tail region that may promote endoplasmic reticulum
      retention.

PMID- 9661663
TI  - Cloning and expression of odorant-binding proteins Ia and Ib from mouse nasal
      tissue.
AB  - We had previously reported the purification and partial characterisation of four
      distinct odorant-binding proteins from male mouse nasal epithelium. One of these,
      named OBP-I appeared to be a heterodimer, whose subunits, Ia and Ib showed
      significant similarity in their N-terminal amino acid sequences with hamster
      aphrodisin. In this paper, we report the complete amino acid sequences of these
      two polypeptide chains, as deduced from nucleotide sequences of their relative
      cDNA. These data confirm the high similarity of both proteins with hamster
      aphrodisin. A comparison with the sequences of other known OBPs indicate that
      they are more closely related to members of class I, including bovine OBP, rat
      OBP-I and pig OBP-I. A putative odorant-binding site is indicated by the presence
      of amino acid residues conserved with respect to the bovine protein, whose three
      dimensional structure has been recently resolved. In-situ hybridisation has
      revealed identical expression patterns for the two proteins, further supporting
      the heterodimeric structure of these proteins in the nasal mucus.

PMID- 9661664
TI  - Polyadenylation of oop RNA in the regulation of bacteriophage lambda development.
AB  - We have shown that Escherichia coli pcnB mutants are lysogenized by bacteriophage
      lambda with lower efficiency as compared to the pcnB+ strains. Our genetic
      analysis revealed that expression of the lambda cII gene is decreased in the pcnB
      mutants. However, using various lacZ fusions we demonstrated that neither
      activities of pL and pR promoters nor transcription termination at tR1 were
      significantly impaired in the pcnB- host. On the other hand, we found that oop
      RNA, an antisense RNA for cII expression, is involved in this regulation. Primer
      protection experiments revealed that oop RNA was polyadenylated and that this
      polyadenylation was impaired in the pcnB mutant. We found that the oop RNA was
      more abundant in the pcnB mutant than in the pcnB+ strain. Furthermore, we showed
      that activity of the pO promoter was not stimulated in the pcnB mutant. Such
      findings indicated that degradation of oop RNA in the pcnB strain was slower
      because of inefficient polyadenylation, which could lead to more effective
      inhibition of cII expression by the antisense oop RNA, resulting in less
      efficient lysogenization of the host. The oop RNA was found previously to play a
      role in phage lambda development only under conditions of overproduction of this
      transcript. Here we demonstrate for the first time, the physiological function of
      oop RNA in lambda development, confirming that this short transcript plays an
      important role in the negative regulation of cII gene expression during lambda
      infection. Moreover, polyadenylation of oop RNA is one of very few known examples
      of specific RNA polyadenylation by PAP I in prokaryotic cells and its role in
      gene expression regulation.

PMID- 9661666
TI  - A broad-host-range Flp-FRT recombination system for site-specific excision of
      chromosomally-located DNA sequences: application for isolation of unmarked
      Pseudomonas aeruginosa mutants.
AB  - An improved method for gene replacement in Pseudomonas aeruginosa was developed.
      The method employs several new gene replacement vectors that incorporate (1) the
      counterselectable sacB marker, (2) a lacZ alpha-allele for blue-white screening,
      (3) the pUC18/19 vectors multiple cloning site with 10 unique restriction sites,
      (4) an oriT for conjugation-mediated plasmid transfer and (5) carbenicillin,
      gentamicin (Gm) and tetracycline selectable markers. A cassette was constructed
      that contains a GmR selectable marker next to the green fluorescent protein
      structural gene, with both markers being flanked by Flp recombinase target (FRT)
      sites. The FRT cassette was used to insertionally inactivate the cloned P.
      aeruginosa pabC gene encoding aminodeoxychorismate lyase. After conjugal transfer
      into P. aeruginosa, plasmid integrants were selected, and deletion of unwanted
      DNA sequences was promoted by sucrose counterselection. The FRT cassette was
      excised with high frequencies (close to 100%) from the chromosome after conjugal
      transfer of a Flp recombinase-expressing plasmid; this sacB-containing plasmid
      was subsequently cured by sucrose counterselection, resulting in an unmarked P.
      aeruginosa delta pabC strain.

PMID- 9661665
TI  - Physical linkage of the human growth hormone gene family and the thyroid hormone
      receptor interacting protein-1 gene on chromosome 17.
AB  - A P1 cloned insert of about 85.5 kilobases (kb) was isolated, containing four
      members of the human growth hormone/chorionic somatomammotropin (GH/CS) gene
      family and the thyroid hormone receptor interacting protein (TRIP-1) gene. The
      presence of the CS-like, CS-A, GH-variant and, most downstream, CS-B gene was
      confirmed by DNA blotting and sequence analysis. The TRIP-1 gene was detected 40
      kb downstream of the CS-B gene and in the reverse transcriptional orientation to
      all the GH/CS genes. The TRIP-1 gene is highly homologous to the SUG-1 gene in
      yeast and is evolutionarily conserved among several species. Based on the common
      location of the GH and TRIP-1 (or homologue) genes on the same chromosome in the
      human, pig and rat genomes, we suggest that these loci are physically linked.
      Previously, it was reported that a muscle-specific sodium channel (SCN4A) gene is
      located immediately upstream of the pituitary growth hormone (GH-N) gene, and is
      linked to the GH gene locus in both humans and rats. This suggests a further
      linkage between the SCN4A, GH and TRIP-1 loci. Also, deoxyribonuclease
      hypersensitive sites have been reported in and around these loci and were
      associated with an important locus control region for the GH/CS genes. Unlike the
      GH/CS genes, we show, using reverse transcriptase-polymerase chain reaction that
      the TRIP-1 gene is expressed ubiquitously and, through RNA blotting, as a 1.4-kb
      transcript. This implies an open and active chromatin structure. The possible
      effect of this structure on the adjacent human GH/CS gene locus is discussed.

PMID- 9661667
TI  - Expression of Reticulomyxa filosa alpha- and beta-tubulins in Escherichia coli
      yields soluble and partially correctly folded material.
AB  - Tubulins are highly conserved multidomain proteins that have to interact with
      eukaryotic chaperonins to gain their correct three-dimensional conformation. The
      prokaryotic chaperonin system of GroEL/ES is able to generate intermediate
      folding states but not natively folded tubulin. To create a system for studying
      these folding intermediates, tubulins from the giant amoeba Reticulomyxa filosa
      (alpha 2- and beta 2-tubulin) were expressed in Escherichia coli singly or in
      tandem. In all cases, soluble tubulin was generated in amounts of 5-10 mg/l
      culture. This is the first reported expression of soluble tubulin in bacterial
      cells. Of particular interest was the observation that upon coexpression with R.
      filosa beta 2-tubulin, proteolytic degradation of alpha 2-tubulin was reduced and
      more full-length product remained intact. This observation points to a specific
      interaction of alpha 2- and beta 2-tubulins in the E. coli cell. The sites of
      interaction are most probably the same that are responsible for the binding of
      native alpha 2- and beta 2-tubulin. The established expression system therefore
      seems well suited for further studies concerning the folding of tubulins.

PMID- 9661668
TI  - Molecular cloning and characterization of a human protein kinase that
      specifically activates c-Jun N-terminal kinase.
AB  - The c-Jun N-terminal kinases (JNKs), also called stress-activated protein kinases
      (SAPKs), belong to the mitogen-activated protein kinase (MAPK) gene super-family.
      Like all the MAPKs, JNKs are activated through dual phosphorylation of a
      theronine residue and a tyrosine residue by a dual specificity kinase such as
      JNKK1/MKK4/SEK1. Here, we report the molecular cloning and characterization of
      hJNKK2 alpha, a human homolog of the recently reported murine MKK7 alpha. hJNKK2
      alpha belongs to the MAPK kinase gene family and is expressed in many adult
      tissues. It is nearly identical to a recently reported human JNKK2 at the kinase
      domain but with major differences in both amino- and carboxyl-terminal sequences,
      suggesting that hJNKK2 alpha may be an alternative spliced form of this kinase.
      Expression of hJNKK2 alpha, but not its related kinases JNKK1/MKK4/SEK1, MEK1,
      MKK3, or MKK6, leads to strong activation of JNK in several cell lines. No
      activation of ERK or p38 kinases was observed with this kinase. An in-vitro
      kinase assay demonstrated that JNK1 activation by hJNKK2 alpha requires
      phosphorylation of the theronine and tyrosine residues at positions 183 and 185
      in JNK1. Furthermore, hJNKK2 alpha activated the JNK-dependent signal
      transduction pathway in vivo by induction of c-Jun- and ATF2-mediated gene
      transcription. In conclusion, we have cloned the human homolog of murine MKK7
      alpha, which may be an alternative spliced form of human JNKK2 involved in
      transducing specific upstream signals to regulate JNK activity in vivo.

PMID- 9661669
TI  - Structure and expression of the human MTG8/ETO gene.
AB  - Translocations involving the putative proto-oncogene MTG8/ETO on 8q22 are
      frequently found in acute myeloid leukemia. To date, little is known of the
      genomic organization of this gene. Here, we report that the MTG8 gene consists of
      13 exons distributed over 87 kb of genomic DNA. Two polymorphic microsatellite
      repeats are described, including one in intron 3 (three alleles; heterozygosity
      0.34) and another in the 3'UTR (15 alleles; heterozygosity 0.89). Expression of
      MTG8 was detected in a variety of normal human tissues with the highest mRNA
      levels occurring in brain and heart. Previously, two mRNA forms produced by the
      alternative usage of the first exon have been reported. We now describe a novel,
      abundantly expressed, alternatively spliced transcript resulting from the
      inclusion of a 155-bp exon (designated 9a) that changes the reading frame and
      introduces a premature stop codon. Identical alternatively spliced mRNA variants
      were found to be produced by the highly conserved homologous gene (Cbfa2t1) in
      the mouse, suggesting an evolutionary significance.

PMID- 9661670
TI  - Bacillus licheniformis sigB operon encoding the general stress transcription
      factor sigma B.
AB  - The general stress response of the Gram-positive soil bacterium Bacillus subtilis
      is controlled by the sigma B transcription factor. sigma B activity is regulated
      by the newly discovered partner switching mechanism of signal transduction, which
      integrates the two different classes of challenges which posttranslationally
      activate sigma B: environmental stress and energy stress. Our investigation of a
      possible sigma B homologue in the related soil bacterium B. licheniformis had two
      goals. First, this study would contribute to understanding the distribution of
      the sigma B general stress system among Gram-positive bacteria. Second, a
      phylogenetic comparison of regulatory systems can supplement genetic and
      biochemical analysis by revealing conserved features that are critical for
      function. We report here that (1) B. licheniformis cells contain a protein that
      closely resembles B. subtilis sigma B in size and antigenic properties; (2) the
      level of this potential sigma B homologue rapidly increases following
      environmental or energy stress; and (3) the B. licheniformis genome encodes a
      homologue of the sigB general stress operon, including the sigma B structural
      gene and seven rsb regulatory genes. Based on these results, B. licheniformis
      possesses a general stress system likely regulated by two coupled partner
      switching modules that sense and integrate the two broad classes of activating
      stress signals.

PMID- 9661671
TI  - Identification and characterization of the gene for Drosophila L3 ribosomal
      protein.
AB  - A cDNA clone that encodes a Drosophila homologue of ribosomal protein L3 was
      isolated from a Drosophila ovary gridded cDNA library. The Drosophila ribosomal
      protein L3 gene (RpL3) is highly conserved with ribosomal protein L3 genes in
      other organisms. It is a single copy gene and maps to position 86D5-10 on
      polytene chromosomes. A Minute gene in this region, M(3) 86D, is a possible
      candidate to encode RPL3. RPL3 message is expressed ubiquitously. A partial RPL8
      cDNA clone was also isolated and mapped to 62F.

PMID- 9661672
TI  - Rapid expression screening of Caenorhabditis elegans homeobox open reading frames
      using a two-step polymerase chain reaction promoter-gfp reporter construction
      technique.
AB  - In this paper a description is given of the expression pattern of the
      Caenorhabditis elegans homeobox gene ceh-38 using GFP reporter constructs, which
      were generated using a two-step polymerase chain reaction (PCR) procedure. This
      method allows fast analysis of genes of interest by looking at their expression
      in vivo using their putative promoter region to control the expression of a
      reporter gene. In this case the method was applied to screen C. elegans homeobox
      containing genes to identify those that are expressed in the head and nervous
      system. The C. elegans genome project has made rapid progress, and more than 79
      megabases of genomic data with several thousand open reading frames are
      available. This information can be used to design primers from putative promoter
      regions, which are amplified using long-range PCR. The long-range PCR product is
      then directly joined to the vector in a long-range Fill-in PCR. Since many genome
      projects are advancing rapidly, this approach should also be applicable for other
      model systems, and the method lends itself to automation, since no gel
      purification steps are necessary. ceh-38 is a member of the ONECUT class of
      homeobox genes. Expression of ceh-38 starts during embryogenesis. In larvae and
      adults, expression was seen in many different types of tissues, such as the
      pharynx, gut, hypodermis and many nerve cells.

PMID- 9661673
TI  - The Streptomyces coelicolor sporulation-specific sigma WhiG form of RNA
      polymerase transcribes a gene encoding a ProX-like protein that is dispensable
      for sporulation.
AB  - In the non-motile mycelial organism Streptomyces coelicolor A3(2), the
      sporulation gene whiG encodes a protein that closely resembles RNA polymerase
      sigma factors such as sigma D of Bacillus subtilis, which mainly control motility
      and chemotaxis genes. Here, we show that the whiG gene product, purified from an
      Escherichia coli strain carrying an expression construct, could activate E. coli
      core RNA polymerase in vitro to transcribe a sigma D-dependent motility-related
      promoter from B. subtilis. Such RNA polymerase holoenzyme preparations could also
      transcribe from an S. coelicolor promoter, PTH4, previously shown to require an
      intact whiG gene for in-vivo transcription. The in-vivo dependence on whiG was
      therefore shown to be direct. Unusually, the initiation of PTH4 transcription in
      vitro depended on the provision of appropriate dinucleotides. The whiG-dependent
      PTH4 transcription unit consisted of a single gene, orfTH4. Sequence comparisons
      suggested that the gene product was a member of a small group of proteins that
      include the B. subtilis and E. coli ProX proteins. Though none of these proteins
      shared more than about 30% of extended primary sequence identity, they had
      similar size and hydropathy profiles, and could be aligned end to end to reveal a
      mosaic of similarities. The ProX proteins of B. subtilis and E. coli are
      implicated in glycine betaine transport in response to hyperosmotic stress.
      However, disruption of orfTH4 did not cause any obvious phenotypic changes in
      growth or development on media of varying osmotic strengths.

PMID- 9661674
TI  - Isolation and characterization of a gene for assimilatory sulfite reductase from
      Arabidopsis thaliana.
AB  - Sulfite reductase (SIR) represents a key enzyme in sulfate assimilation in higher
      plants. The genomic DNA sequence of the sir gene from Arabidopsis thaliana
      including regulatory and structural regions was isolated and characterized. The
      sequence of a 6 kb fragment encoding SIR revealed a coding region of 2891
      basepairs (bp) that consists of eight exons separated by seven introns between 83
      and 139 bp in length. The transcription start point was determined 272 bp
      upstream of the translation start site. Southern analysis indicates a single
      locus for the sir gene that gives rise to a 2.4 (kb) mRNA in leaves and in roots.
      The promoter region was verified by functional expression of the gusA reporter
      gene in transgenic A. thaliana plants and was shown to provide correct expression
      in root and leaf.

PMID- 9661675
TI  - Asthma: a longitudinal perspective.
AB  - In the future, the important longitudinal studies will be those that divide the
      broad spectrum of asthma into phenotypic groups in order to provide more precise
      information about mechanisms and outcomes. Asthmatics who present in a clinical
      setting often have a combination of two or three different phenotypes, and may
      have more severe illness as a result, but subjects who are tested in
      epidemiological studies are frequently characterized by only one phenotype.
      Although the definition of asthma as a combination of symptoms plus either AHR or
      reduced lung function has greater predictive isolation for assessing the
      prognosis of respiratory illness that occurs in childhood (27,40,55,66-68),
      studies that are able to classify subjects according to their different
      phenotypes are more likely to lead to a better understanding of the factors that
      influence prognosis. More importantly, by using this approach, future research
      studies should be better able to separate the mechanisms whereby therapeutic or
      environmental interventions influence the prognosis of each phenotype. The
      potential benefits will be a better understanding and evaluation of the factors
      that make an important contribution to respiratory health.

PMID- 9661676
TI  - Clinical implication of protein levels of IL-5 in induced sputum in asthmatic
      patients.
AB  - To determine whether protein levels of interleukin-5 (IL-5) in induced sputum
      reflect the degree of eosinophilic inflammation, we evaluated the role of IL-5 on
      clinical characteristics in stable asthmatic patients. IL-5 level, differential
      eosinophil count, and level of eosinophil cationic protein (ECP) in induced
      sputum were all significantly higher for asthmatics than for normal controls.
      Both eosinophil counts and ECP levels in induced sputum were inversely correlated
      with the degree of airflow limitation (FEV1/FVC). In addition, patients with
      measurable IL-5 in sputum had significantly more eosinophils, higher levels of
      ECP in sputum, and lower FEV1 (percent predicted) than did patients with levels
      of IL-5 beneath the limit of detection. However, we found no significant
      difference in IL-5 levels between atopic and nonatopic asthmatics. IL-5 level in
      induced sputum is a good indicator of eosinophilic inflammation in atopic and
      nonatopic asthmatic patients.

PMID- 9661677
TI  - Perception of natural fluctuations in peak flow in asthma: clinical severity and
      psychological correlates.
AB  - Two methods of defining perception of asthma-related changes in airflow were
      compared, and relationships to clinical opinions of severity and assessments of
      psychological functioning were investigated. Perceived breathlessness (VAB) and
      peak expiratory flow (PEF) were recorded by 100 subjects for 28 days. Perception
      was defined by correlation of the two values and by the ratio of maximum change
      in PEF and related change in VAB. The latter method defined 24 poor perceivers
      (PP) and 13 exaggerated perceivers (EP), in whom presence of a psychological
      disorder was high (30% of PP, 54% of EP, compared to 8% of the remainder).
      Clinical severity in EP was assessed as greater than appeared warranted.

PMID- 9661678
TI  - Human corticotropin-releasing hormone improves overnight FEV1 in nocturnal
      asthma.
AB  - Corticotropin-releasing hormone (CRH) exhibits anti-inflammatory properties
      independent of its effect on adrenal function. We investigated the safety and
      effect of CRH in nocturnal asthma, a disease where inflammation is prominent.
      Five subjects underwent an overnight infusion of placebo on the first night, CRH
      at a 2.5 micrograms/kg/hr on the second night, and three subjects received CRH at
      4.0 micrograms/kg/hr on the third night. A significant improvement occurred in
      overnight change in forced expiratory volume 1 sec. % (delta FEV1) with CRH
      (+17.4 +/- 9.1%) as opposed to placebo (-25.9 +/- 7.1%), p = 0.024, CRH was well
      tolerated. Further research with CRH may clarify the pathophysiology of nocturnal
      asthma.

PMID- 9661679
TI  - Inhibitory effect of ambroxol on superoxide anion production and generation by
      murine lung alveolar macrophages.
AB  - We examined the effect of ambroxol on superoxide anion production before and
      generation after phorbol-myristate acetate (PMA) stimulation of lung alveolar
      macrophages. Lung free cells including lung alveolar macrophages were obtained
      from Fischer 344 rats and guinea pigs using bronchoalveolar lavage. The
      superoxide anion produced by lung alveolar macrophages with or without
      stimulation of PMA was measured by lucigenin-dependent chemiluminescence method
      using a photon counter. Ambroxol inhibited the superoxide anion production and
      generation by lung alveolar macrophages harvested from both F344 rats and guinea
      pigs in a dose-dependent fashion. Approximately 16 mumol/L of ambroxol inhibited
      50% of superoxide production of lung alveolar macrophages in rats and guinea
      pigs, whereas a slightly greater dose of ambroxol, i.e., 18-26 mumol/L, was
      necessary to inhibit 50% of PMA-enhanced superoxide generation by lung alveolar
      macrophages. These results suggest that ambroxol acts as an antioxidant in murine
      lungs and may be a potential therapeutic option for reactive oxygen species
      associated lung disorders including bronchial asthma.

PMID- 9661680
TI  - Assessment of the inhalation technique in outpatients with asthma or chronic
      obstructive pulmonary disease using a metered-dose inhaler or dry powder device.
AB  - Inhaled medication is commonly prescribed for the treatment of asthma and chronic
      obstructive pulmonary disease (COPD), but is often not properly used by patients.
      A total of 316 patients suffering from asthma or COPD took part in a study that
      evaluated how patients utilized their metered-dose inhaler (MDI) or dry powder
      inhaler, using a standardized inhaler checklist. Two hundred eighty-one patients
      (88.9%) made at least one mistake in the inhalation technique. The mistakes were
      classified into skill and nonskill mistakes. Two hundred patients made one or
      more skill mistakes and 81 patients only made one or more nonskill mistakes. The
      most common skill error was "not continuing to inhale slowly after activation of
      the canister" (69.6%). The nonskill item most patients had difficulties with was
      "exhale before the inhalation" (65.8%). Patients who used an MDI made
      significantly fewer nonskill mistakes than patients using a dry powder device.
      Older patients had more difficulty with the correct use of the inhaler than
      younger patients. There was no difference in errors between men and women. In
      this patient sample, most patients failed to use their inhaler correctly. Regular
      instructions and checkups of inhalation technique are the responsibility of the
      physician and should be a standard and routine procedure.

PMID- 9661682
TI  - Prevalence of bronchial asthma in schoolchildren in Delhi.
AB  - There is a paucity of information on the prevalence of asthma in children in
      India. Some evidence suggests that asthma is less common in developing than in
      the developed countries. The present study was carried out to estimate its
      current magnitude in children in Delhi. The questionnaire-based study was carried
      out in two randomly selected schools in Delhi. All the children were eligible.
      The age range was 4-17 years. The questionnaires were distributed to all the
      children present (n = 2867) to be answered by either parent. The key questions
      were related to complaints of recurrent wheezing in the past, in the last 1 year,
      and also wheezing exclusively induced by exercise or colds. In all, 2609
      questionnaires were completed and returned (response rate 91%). There was a
      slight excess of males (54%). The prevalence of current asthma was 11.6% and past
      asthma was reported by 4.1% of children, giving a cumulative prevalence of 15.7%.
      Exclusive exercise-induced asthma was 2.8% and that associated with colds, 2.3%.
      The current prevalence of all wheezing was thus 16.7% and cumulative prevalence
      was 20.8%. While there was no sex-related difference in prevalence, wheezers were
      the highest in the 9-13 year age group. A significant association was found
      between the prevalence of wheezing and a family history of asthma (odds ratio
      3.65) and presence of smokers in the family (odds ratio 1.62). When both the
      above factors combined, the odds ratio for risk of asthma was 4.58. There was no
      significant association with any economic class. Only 11% of asthmatics had been
      labeled so by their physicians. The prevalence of bronchial asthma and wheezing
      in children in Delhi is quite high and comparable to that reported from several
      developed countries. A positive family history of asthma and presence of smokers
      in the family emerged as significant risk factors.

PMID- 9661681
TI  - Insights into asthma prevalence in Oregon.
AB  - Asthma is one of the most common chronic diseases. The prevalence of asthma
      appears to be increasing. National data have suggested that Oregon's asthma
      mortality rate has been twice as high as the national average. The prevalence and
      impact of asthma are not systematically assessed or tracked within Oregon. We
      estimated the current asthma prevalence and mortality using data from statewide
      hospital discharge data, the 1995 Behavioral Risk Factor Surveillance Survey, and
      school registration data from the Portland area. A conservative estimate of
      Oregon's current asthma prevalence is 6-7% and lifetime asthma prevalence is
      estimated at 6-11% for both adults and children. It appears that current asthma
      prevalence increases during adolescence. The Willamette Valley, an area known for
      high pollen counts, does not have a higher rate of hospital discharges per capita
      than other areas within the state. Oregon's apparent higher asthma mortality may
      be the result of the Oregon State Health Division's aggressive policies toward
      accurate reporting on death certificates. Oregon's age distribution may also
      contribute to the apparent higher asthma mortality rate.

PMID- 9661683
TI  - Handling of a spacer (Babyhaler) for inhalation therapy in 0- to 3-year-old
      children.
AB  - The handling of the Babyhaler spacer for inhalation therapy in children 0-3 years
      old with asthma was tested and the perceptions of the investigators with the
      instruction of this device to the parents was investigated. It was an open,
      multicenter study of 182 patients with a treatment period of 2 weeks and a 2-week
      follow-up period. Thirty pediatricians in Dutch local and university hospitals
      participated. Using a standardized instruction, the purpose and the application
      of the Babyhaler were explained and demonstrated, and parents were asked to use
      the Babyhaler on their own child. The quality of the demonstration was scored
      and, if necessary, additional instruction was given. In the following treatment
      period of 2 weeks record card was completed; the convenience score of the
      Babyhaler and the symptom score were recorded. At the following evaluation visit
      the handling of the Babyhaler by the parents was re-evaluated. Eighty-nine
      percent of the parents could use the Babyhaler correctly after one instruction.
      The instructions of the Babyhaler were considered to be easy in 83% of the cases
      by the parents and the investigators. During the treatment period the handling
      score (6 = impossible to use, 1 = very easy) improved from 2.4 to 1.7. At the
      evaluation visit the correct use was similar to the result at the instruction
      visit (87%). No differences were found in the ease of handling between the three
      age groups (0-1, 1-2, and 2-3 years). The application of inhalation therapy via
      the Babyhaler was favored by 92% of the parents as compared to the former
      treatment method. We demonstrated that the Babyhaler is easy to use by the
      parents and that the instruction of the device by practitioners is also perceived
      as easy.

PMID- 9661684
TI  - Do we know when to transfuse red cells to treat acute anemia?

PMID- 9661685
TI  - A pilot randomized trial comparing symptomatic vs. hemoglobin-level-driven red
      blood cell transfusions following hip fracture.
AB  - BACKGROUND: The indications for transfusion have never been evaluated in an
      adequately sized clinical trial. A pilot study was conducted to plan larger
      clinical trials. STUDY DESIGN AND METHODS: Hip fracture patients undergoing
      surgical repair who had postoperative hemoglobin levels less than 10 g per dL
      were randomly assigned to receive 1) symptomatic transfusion: that is,
      transfusion for symptoms of anemia or for a hemoglobin level that dropped below 8
      g per dL or 2) threshold transfusion: that is, patients receive 1 unit of packed
      RBCs at the time of random assignment and as much blood as necessary to keep the
      hemoglobin level above 10 g per dL. Outcomes were 60-day mortality, morbidity,
      functional status, and place of residence. RESULTS: Among 84 eligible patients
      enrolled, mean (+/- SD) prerandomization hemoglobin was 9.1 (+/- 0.6) g/ dL. The
      median number of units transfused in the threshold transfusion group was 2
      (interquartile range, = 1-2), and that in the symptomatic transfusion group was 0
      (6; interquartile range, = 0-2) (p < 0.001). Mean hemoglobin levels were
      approximately 1 g per dL higher in the threshold group than in the symptomatic
      group: for example, on Day 2, 10.3 (+/- 0.9) g per dL versus 9.3 (+/- 1.2) g per
      dL, respectively (p < 0.001). At 60 days, death or inability to walk across the
      room without assistance occurred in 16 (39.0%) of the symptomatic transfusion
      group and 19 (45.2%) of the threshold transfusion group. Death occurred by 60
      days in 5 (11.9%) of the symptomatic transfusion group and 2 (4.8%) in the
      threshold transfusion group (relative risk = 2.5; 95% CI, 0.5-12.2). Other
      outcomes were similar for the two groups. CONCLUSIONS: Symptomatic transfusion
      may be an effective blood-sparing protocol associated with the transfusion of
      appreciably fewer units of RBCs and lower mean hemoglobin levels than are
      associated with the threshold transfusion policy. However, it is unknown whether
      these two clinical strategies have comparable mortality, morbidity, or functional
      status. A definitive trial is needed.

PMID- 9661686
TI  - The Collaborative Hospital Transfusion Study: variations in use of autologous
      blood account for hospital differences in red cell use during primary hip and
      knee surgery.
AB  - BACKGROUND: Red cell use in patients undergoing Diagnosis Related Group (DRG) 209
      procedures (major joint and limb reconstruction procedures of the lower
      extremities) has been shown to have large, unexplained interhospital variations.
      STUDY DESIGN AND METHODS: Abstracted records of 2590 consecutive DRG 209 patients
      at five university hospitals from January 1992 to December 1993 were stratified
      by procedure and preoperative blood deposit status. Patient characteristics and
      transfusion and in-hospital outcomes were compared across hospitals. RESULTS:
      Blood use among patients who did not preoperatively deposit blood was similar
      across hospitals. Significant differences were found across hospitals for total
      hip replacement patients in the percentage of patients preoperatively depositing
      blood (59-80%), percentage of patients receiving transfusion(s) (51 to > 99%),
      the mean number of units collected per patient (1.6-2.9), and the mean number of
      unused autologous units per 100 patients (1-185). No significant differences were
      found in the percentage of those who deposited blood and then required allogeneic
      units. There was little variability in length of hospital stay or in last
      hematocrits. Findings were similar for total knee replacement patients.
      CONCLUSIONS: Interhospital variations in red cell use for primary total hip and
      knee reconstruction are primarily due to hospital-specific differences in
      autologous blood collection and transfusion.

PMID- 9661687
TI  - A randomized, controlled trial to study the efficacy and safety of C1 inhibitor
      concentrate in treating hereditary angioedema.
AB  - BACKGROUND: No effective treatment exists in the United States for acute attacks
      of hereditary angioedema (HAE). STUDY DESIGN AND METHODS: To evaluate the
      efficacy and safety of C1 inhibitor concentrate in treating HAE, a large primary
      care and referral center hospital conducted a randomized, placebo-controlled,
      double-blind trial with intent-to-treat analysis. Of the 36 patients enrolled in
      the study, 23 received treatment, and 22 completed the trial. C1 inhibitor
      concentrate or albumin (placebo) infusions were administered in a blind fashion
      to HAE patients who came to the hospital for treatment no later than 5 hours
      after an attack began. RESULTS: Relief was almost twice as fast in persons
      receiving C1 inhibitor concentrate than in the controls: 7.62 hours (mean; SD
      7.08) versus 15.35 hours (mean; SD 8.31), respectively. The difference for time
      to-relief was highly significant (p = 0.007, Mann-Whitney U test). The median
      time-to-relief was 6.17 hours (interquartile range 0.33-15.35) in the treatment
      group and 15.35 hours (interquartile range 14.00-22.83) in the control group.
      Resolution of symptoms was one-third faster in the C1 inhibitor concentrate group
      than in the placebo group: 23.98 hours (mean; SD 14.81) and 34.58 hours (mean; SD
      13.56), respectively (p = 0.09, Mann-Whitney U test). Recovery of functional C1
      inhibitor was 119.65 percent (mean; SD 50.80), and half-life was 37.87 hours
      (mean; SD 19.75). Recovery of antigenic C1 inhibitor was 147.75 percent (mean; SD
      97.68), and half-life was 24.01 hours (mean; SD 9.70). There were no viral
      infections or serious adverse effects from the drug after 70 attacks in the
      treatment group and 96 attacks in the control group. CONCLUSIONS: C1 inhibitor
      concentrate is a safe, effective treatment for acute attacks of HAE.

PMID- 9661688
TI  - Survival of fresh human platelets in a rabbit model as traced by flow cytometry.
AB  - BACKGROUND: In the event of hemorrhage and blood loss, platelets play a vital
      role in the coagulation process. However, there are currently no acceptable
      protocols for long-term storage of platelets. As a first step toward testing the
      efficacy of stored platelets or platelet substitutes in vivo, a flow cytometric
      technique was developed to detect human platelets in rabbit blood. STUDY DESIGN
      AND METHODS: Human platelets were transfused to rabbits whose reticuloendothelial
      system was inhibited by the administration of ethyl palmitate. Because human and
      rabbit platelets display surface molecules with different epitopes, human
      platelets were selectively labeled with antibodies specific for glycoprotein IX
      (CD42a). As this antibody does not label rabbit platelets, it allows
      discrimination of human from rabbit platelets in samples of rabbit blood
      containing both types of platelets. RESULTS: Survival of human platelets in
      rabbits was monitored by flow cytometry and fluorescence microscopy in blood
      drawn at various times after the platelet transfusion. Fresh human platelets
      transfused to untreated control rabbits (n = 3) were removed from circulation
      within 10 minutes of the completion of the transfusion. Fresh platelets (1 day
      old) transfused to rabbits treated with ethyl palmitate (n = 5) survived for 24
      hours with an average half-life of 8.6 hours. In contrast, 8-day-old platelets
      were cleared from the circulation sooner with an average half-life of 2.9 hours
      (n = 4). CONCLUSION: This report describes a rapid and efficient method of
      assessing the survival of human platelets in a rabbit model using flow cytometry.
      This technique will enable the monitoring in rabbits of human platelets prepared
      by various preservation protocols.

PMID- 9661689
TI  - Granulocyte collection efficiency and yield are enhanced by the use of a higher
      interface offset during apheresis of donors given granulocyte-colony-stimulating
      factor.
AB  - BACKGROUND: Trials evaluating granulocyte transfusions for therapy of febrile
      neutropenia demonstrated mixed clinical results, which may in part be due to the
      low neutrophil cell dose of the transfused components. To optimize the latter
      variable, the effect of various interface offset (IO) settings during apheresis
      on granulocyte collection efficiency (GCE) and yield was determined in normal
      donors given granulocyte-colony-stimulating factor (G-CSF). STUDY DESIGN AND
      METHODS: Seventeen donors underwent 44 granulocyte collections performed with a
      continuous-flow blood cell separator with hetastarch infusion after stimulation
      with G-CSF (5 micrograms/kg/day). Apheresis was performed alternatively using one
      of three IO settings: IO = 15 (Group 1, n = 16), IO = 25 (Group 2, n = 12), and
      IO = 35 (Group 3, n = 13). The GCE and yield and changes in donor platelet count,
      hematocrit (Hct), and red cell (RBC) volume of the components were compared among
      the three groups. RESULTS: The mean GCE was greater (p = 0.006) during apheresis
      at an IO setting of 35 (60 +/- 12%) than at an IO setting of 15 (40 +/- 17%). The
      mean granulocyte yield (x10(10) per procedure was 10.8 +/- 2.95 at an IO setting
      of 35 and 7.73 +/- 4.02 at an IO setting of 15 (p = 0.08). In a multivariate
      linear regression model, factors independently associated with granulocyte yield
      were the absolute granulocyte count (r = 0.73, p < 0.001) and blood volume of the
      donor (r = 0.54, p = 0.001) before the procedure and the use of an IO setting of
      35 (r = 0.50, p = 0.002). There was no significant difference among the three
      groups in the decrement in donor platelet count or Hct with apheresis, although
      the mean RBC volume was greater in Group 3. CONCLUSION: Granulocyte apheresis at
      an IO setting of 35 rather than 15 resulted in a significant increase in the GCE.
      The use of an IO setting of 35 during apheresis was an independent factor
      associated with granulocyte yield in the multivariate model. Donor safety was not
      compromised by collecting granulocytes at the higher IO setting.

PMID- 9661690
TI  - False-positive eluate reactivity due to the low-ionic wash solution used with
      commercial acid-elution kits.
AB  - BACKGROUND: During the use of commercial red cell (RBC) acid-elution kits for
      adsorption and elution (adsorption/elution) studies with anti-D, unexpected
      reactive eluates (anti-D) were obtained from D- RBCs. Such results were not
      obtained with a parallel xylene method or, historically, with heat and ether
      methods. STUDY DESIGN AND METHODS: Single-donor and commercial polyclonal anti-D
      samples were incubated with D+ and D- RBCs. Acid eluates were prepared by the
      manufacturers' directions. Variations in the wash step of the eluate preparation
      included the use of commercial kit wash solution versus phosphate-buffered saline
      versus solutions of various ionic strengths. RESULTS: Anti-D was eluted from 20
      of 22 samples of D- RBCs after incubation with commercial polyclonal anti-D
      (titer 512) and from 2 of 3 samples of D- RBCs incubated with single-donor anti-D
      (titer 256). With a low-titer (16) single-donor anti-D, 0 of 4 eluates from D-
      RBCs reacted. When phosphate-buffered saline was substituted for the commercial
      wash solution, 0 of 11 D- RBC eluates reacted, as compared with 9 of 11 D- RBCs
      that yielded positive 1+(-)2+ eluates with the commercial wash solution. If the
      recommended initial phosphate-buffered saline wash was omitted before the use of
      the commercial wash solution, the eluate reactivity was stronger (2+(-)3+). When
      low-ionic-strength (< 0.03 M) saline was substituted, anti-D was eluted from D-
      RBCs. All last washes were nonreactive. Antiglobulin tests on all adsorbing D-
      were negative. CONCLUSION: Commercial wash solutions used for acid elution are at
      low ionic strength and commonly yield superior eluates, but in the presence of
      high-titer antibodies, false-positive eluates can result. It is our belief that
      the low-ionic-strength wash solution caused aggregation of IgG and nonspecific
      attachment of IgG on RBCs. Aggregates will contain IgG serum antibodies in
      proportion to the titer of the antibody. It is this nonspecifically bound
      antibody that is eluted from antigen-negative RBCs.

PMID- 9661691
TI  - Hepatitis A virus infections associated with clotting factor concentrate in the
      United States.
AB  - BACKGROUND: Two cases of hepatitis A among persons exposed to the same lot of
      solvent/detergent-treated antihemophilic factor VIII concentrate were reported to
      a surveillance system. An investigation was conducted to find additional cases
      and determine the source of infection. STUDY DESIGN AND METHODS: A seroprevalence
      study was conducted among persons with exposure to the suspect lot for serologic
      evidence of recent infection with hepatitis A virus (HAV). RESULTS: Six cases of
      recent HAV infection were discovered: four of the patients had been infused with
      material from the suspect lot of factor VIII, and two had received infusions of
      factor IX concentrate made from plasma pools common to the suspect factor VIII
      lot. HAV was identified in one of the plasma pools, in the factor VIII product,
      and in serum or stool from two factor VIII recipients and one factor IX
      recipient. The genetics sequence of the virus in the plasma pool, the factor VIII
      lot, and the factor VIII recipients were identical, while that of the virus in
      the factor IX recipient differed by a single base. CONCLUSION: These data
      document the transmission of HAV by a factor VIII concentrate and implicate
      factor IX products manufactured from a common source-plasma pool.

PMID- 9661692
TI  - Distribution of HIV type 1 (HIV-1) in blood components: detection and
      significance of high levels of HIV-1 associated with platelets.
AB  - BACKGROUND: Although inactivation of enveloped viruses transmitted by plasma
      derivatives has been successful, no methods for virus inactivation or removal
      have been established for platelet concentrates or red cell (RBC) components.
      Relatively little is known regarding the extent or significance of virus
      interactions with the cellular constituents in these components. STUDY DESIGN AND
      METHODS: Units of whole blood were collected from six HIV type 1 (HIV-1)
      positive, asymptomatic individuals and separated into peripheral blood
      mononuclear cells (PBMNCs), cell-free plasma, white cell-reduced platelet
      concentrate, and white cell-reduced RBCs. DNA and RNA polymerase chain reaction
      and virus culture methods were used to study the compartmentalization of HIV-1
      immediately after component preparation and after storage. RESULTS: As expected,
      HIV DNA and infectious virus were detected in fresh blood and in PBMNCs, and
      virion-associated RNA was detected in fresh plasma from all six donors. The
      levels of viral nucleic acids in these preparations remained relatively stable
      with 4 degrees C storage, whereas infectivity of PBMNCs was rapidly lost. Washed
      RBCs tested negative for HIV in all assays at all time points. Platelets retained
      high levels of HIV RNA (but not infectivity) after extensive washing, as well as
      after storage at 4 and 22 degrees C. High-level platelet-associated HIV-1 was
      also demonstrated in samples collected during early seroconversion.
      Periseroconversion and postseroconversion levels of platelet-associated HIV-1
      correlated with the level of plasma viremia and with the rate of progression to
      AIDS. Cell-free virus from donor plasma and tissue culture fluid rapidly and
      firmly attached to platelets from noninfected donors. Infectivity of tissue
      culture virus bound to platelets was demonstrated in vitro. CONCLUSION:
      Significant levels of HIV-1 are associated with platelets during all stages of
      infection. Platelet-associated HIV could either mediate virus clearance or
      facilitate virus dissemination and expanded tropism. Finally, virus inactivation
      research must address virus associations with platelets.

PMID- 9661693
TI  - Antibodies to hepatitis E virus among several populations in Greece: increased
      prevalence in an hemodialysis unit.
AB  - BACKGROUND: Hepatitis E virus (HEV) has been found to be the causative agent of
      enterically transmitted non-A, non-B hepatitis in tropical and subtropical
      countries. Several investigators, however, have indicated that HEV could be
      endemic in Europe, albeit at a low prevalence. STUDY DESIGN AND METHODS: The
      purpose of this study was to estimate the prevalence of anti-HEV in various
      populations in northwestern Greece (Epirus region). Healthy blood donors (2636),
      refugees from southern Albania (350), children (165), injecting drug users (IDUs)
      (65), multiply transfused patients (62), patients with chronic viral hepatitis
      (75), and chronic hemodialysis patients (149) were investigated for anti-HEV by
      enzyme immunoassay and confirmatory Western blot assay. In addition, 380
      consecutive healthy blood donors and 62 hemodialysis patients from a neighboring
      area (Agrinion, Greece) were investigated. RESULTS: A very low presence of anti
      HEV antibody was found among healthy blood donors from Epirus (0.23%) and
      Agrinion (0.53%). Anti-HEV was not detected in children, IDUs, or multiply
      transfused patients. In contrast, a low but significant prevalence of anti-HEV
      was found among refugees (4.85%), patients with chronic viral hepatitis (5.3%),
      and hemodialysis patients from Epirus (1.34%), as compared with healthy blood
      donors from Epirus: p < 0.0001, p < 0.00001, and p < 0.10, respectively. A high
      prevalence (9.7%) of anti-HEV was revealed in patients at the hemodialysis unit
      of the General Hospital of Agrinion (p < 0.00005, compared to healthy blood
      donors from Agrinion). No significant association was found between anti-HEV
      positivity and the age or sex of donors, the duration of hemodialysis, positivity
      for hepatitis B or C virus infection markers, history of hepatitis, increased
      alanine aminotransferase, renal transplantation, a history of transfusion, or the
      number of units transfused. CONCLUSION: This study demonstrated a high prevalence
      of anti-HEV in a separate hemodialysis unit, without an association with the
      known routes of transmission of blood-borne viruses. This observation suggests
      that a still-undefined intra-unit factor or other factors are associated with HEV
      transmission.

PMID- 9661694
TI  - No-fault compensation for transfusion-associated hepatitis B virus, hepatitis C
      virus, and HIV infection: Italian law and the Tuscan experience.
AB  - BACKGROUND: On February 25, 1992, in Italy, a law (Number 210; referred to as
      210/1992) was promulgated providing economic indemnity for persons infected with
      hepatitis B virus, hepatitis C virus, and HIV via transfusion or the
      administration of hemoderivatives. STUDY DESIGN AND METHODS: The requests for
      compensation presented in the central Italian region of Tuscany from the time of
      the law's promulgation through December 31, 1996, were analyzed. These requests
      are surveyed by medical commissions in the regional military hospitals, which
      must compile a report of the completed assessments, formulate a decision
      concerning verified illnesses, and express an opinion on the existence of a
      relationship of causality between the damaging event and the impairment or death
      of the subjects. RESULTS: Out of 428 requests for indemnity, 372 have been
      granted and 56 denied. Posttransfusion infections (286 cases) were clearly more
      prevalent than those due to hemoderivatives (141 cases). Cases of hepatitis,
      particularly type C, constitute the great majority of the infections for which
      indemnity was sought, while cases of HIV infection are scarce and in sharp
      decrease in the data from 1995 and 1996. CONCLUSIONS: Italian Law 210/1992 has
      been recognized as providing a benefit to persons infected medically, but its
      efficiency is greatly obstructed by a lack of documentation regarding
      transfusions performed in the past.

PMID- 9661695
TI  - The red cell transfusion trigger: has a sin of commission now become a sin of
      omission?
AB  - The benefits of a Hct range of 30 to 35 percent include improved oxygen delivery
      and enhanced hemostasis, which help minimize complications in patients at high
      risk for ischemia and perioperative nonsurgical bleeding. In these settings, the
      conservative transfusion practice of using a lower Hct range should be replaced
      with a more aggressive approach. The known risks of blood transfusion would
      appear to be sufficiently low and the benefits sufficiently high to justify
      maintaining a Hct of at least 30 percent. An even higher Hct, of 35 percent, may
      be desirable in patients who have overt cardiopulmonary disease or who are at
      high risk for myocardial ischemia. Many retrospective studies have been conducted
      to persuade us that a conservative transfusion trigger is a safe and prudent
      practice, but retrospective studies are not what we need. What we need is a
      series of well-designed, prospective, randomized trials to evaluate the impact of
      a more aggressive transfusion policy on perioperative mortality, morbidity, and
      nonsurgical bleeding in patients with known cardiopulmonary disease or who are at
      high risk for myocardial and cerebrovascular ischemia.

PMID- 9661696
TI  - Screening blood donors for Trypanosoma cruzi infection in a nonendemic area of
      Brazil.

PMID- 9661697
TI  - Human T-lymphotropic virus types I and II in Africa in 1969.

PMID- 9661698
TI  - Compensatory eythropoiesis during routine autologous blood donation.

PMID- 9661699
TI  - Effects of storage temperature and time on cord blood progenitor cells.

PMID- 9661701
TI  - Induction of fragility at the human RNU2 locus by cytosine arabinoside is
      dependent upon a transcriptionally competent U2 small nuclear RNA gene and the
      expression of p53.
AB  - Chromosomal fragile sites are regions that are intrinsically unstable and are
      susceptible to experimentally induced damage. In most cases, the target and
      mechanism of induction of fragility are unknown. Using ectopic integration of
      engineered DNA arrays to create "new" fragile sites, we and others have
      previously shown that the transcriptionally competent U2 gene is necessary and
      sufficient for induction of fragility at the RNU2 locus upon infection of human
      cells with Adenovirus 12. In the present study we have investigated the response
      of the RNU2 locus to cytosine arabinoside (araC), an inhibitor of DNA polymerases
      and a common inducer of fragile sites. We demonstrate that the RNU2 locus is
      sensitive to the drug and that araC-induced fragility is dependent upon a
      functional U2 gene and on the expression of the cellular p53 protein. Our results
      identify a novel DNA structure associated with fragile sites and suggest a role
      for transcription and repair processes in RNU2 fragility.

PMID- 9661700
TI  - Fanconi anemia group A and D cell lines respond normally to inhibitors of cell
      cycle regulation.
AB  - Cells from patients with Fanconi anemia (FA) show decreased viability and
      decreased chromosome stability after treatment with DNA cross-linking agents,
      compared to normal cells. FA cells also show a relative accumulation at the G2/M
      transition after such treatment. This has suggested a possible checkpoint
      abnormality. In the studies presented here, treatment with hydroxyurea, caffeine
      or inhibitors of cell cycle kinases did not reveal abnormalities in survival or
      chromosome stability in FA-A or FA-D cells. Chromosomal breaks introduced by
      hydrogen peroxide or methyl methanesulfonate accumulated to the same extent in FA
      A or FA-D cells as in normal cells. We conclude that FA-A and FA-D cells respond
      normally to agents known to alter the cell cycle or introduce DNA strand breaks.
      FA cells process strand breaks and a variety of DNA monoadducts normally. Our
      results are compatible with repair of DNA crosslinks being slower in FA than in
      normal cells and FA cells having normal cell cycle checkpoints.

PMID- 9661702
TI  - Demethylation of the human MDR1 5' region accompanies activation of P
      glycoprotein expression in a HL60 multidrug resistant subline.
AB  - Chemotherapy is frequently limited by the development of multidrug resistance, a
      major cause of which is activation of the P-glycoprotein-encoding MDR1 gene. We
      have previously developed a P-glycoprotein-expressing multidrug resistant subline
      (HL60/E8) from the non-P-glycoprotein-expressing human HL60 promyelocytic
      leukemia cell line. A possible cause of MDR1 silencing in HL60 cells is
      methylation of the promoter proximal region, thus demethylation occurring as a
      result of drug treatment may be responsible for MDR1 activation in the multidrug
      resistant subline. Using the bisulphite genomic sequencing technique we
      demonstrated that HL60 DNA is methylated at multiple sites within two distinct
      areas, one upstream and one downstream of the transcription start point. Only a
      single site in each area was methylated in all strands examined, with the
      remaining adjacent sites showing partial methylation. In contrast, DNA from the
      multidrug resistant HL60/E8 subline was unmethylated at essentially all sites in
      both areas. Thus the development of the P-glycoprotein-expressing multidrug
      resistant subline was associated with demethylation of the MDR1 5' region.

PMID- 9661703
TI  - The fidelity of double strand breaks processing is impaired in complementation
      groups B and D of Fanconi anemia, a genetic instability syndrome.
AB  - In mammalian cells, nonhomologous end-joining is the predominant mechanism to
      eliminate DNA double strand breaks. Such events are at the origin of deletion
      mutagenesis and chromosomal rearrangements. The hallmark of Fanconi anemia, an
      inherited cancer prone disorder, is increased chromosomal breakage associated to
      over-production of deletions. Knowing that double strand breaks are at the origin
      of deletion mutagenesis, the question arises whether their processing is affected
      in FA. We set up a "host cell end-joining assay" to analyze the fate of double
      strand breaks into extrachromosomal substrates transiently replicated in normal
      and FA-D lymphoblasts. Although no difference in plasmid survival was found,
      blunt-ended breaks were sealed with significantly lower fidelity in FA cells,
      resulting in a higher deletion frequency and a larger deletion size. The results
      suggest that FA-D and FA-B gene products are likely to play a role in end-joining
      fidelity of specific DNA double strand breaks.

PMID- 9661704
TI  - Exon trapping and sequence-based methods of gene finding in transcript mapping of
      human 4p16.3.
AB  - We have applied exon amplification, GRAIL2 exon prediction and EST database
      searching to a 2 Mb segment of chromosome 4p16.3. Experimental and computational
      methods of identifying exons were comparable in efficiency and apparent false
      positive rate, but were complementary in gene identification, revealing distinct
      overlapping sets of expressed sequences. EST searching was most powerful when we
      considered only those ESTs that show evidence of splicing relative to the genomic
      sequence. The combination of the three gene finding methods produced a
      transcription map of 30 loci in this segment of 4p16.3 that includes known human
      genes, homologs of loci identified in rodents and several anonymous transcripts,
      including a putative novel DNA polymerase and a gene related to Drosophila ash1.
      While most of the genes in the region have been found, our data suggest that even
      with the entire DNA sequence available, complete saturation of the transcript map
      will require additional, focused experimental effort.

PMID- 9661705
TI  - Interdependence and life care planning.
AB  - Today's society is more litigant in accidental injury occurrences. With many
      injuries involving children, malpractice suits have resulted in an influx of
      information and rehabilitation supports. To address the growing need for legal
      representation in life care planning for injured persons, this easily understood
      tool provides the injured party with a viable approach to community
      interdependence and inclusion. Contrary to the conventionally medical model,
      where the person with a disability is viewed as needing 'fixed', this approach
      examines culture, community and the long term effects of disability. The
      individual with a disability is seen and understood within four aspects of
      personhood: capacities, gifts and passions; inclusive relationships; personal
      involvement; and understanding their culture and community. This life care
      planning process examines five eras in one's life cycle: formative/school age
      years, early work years, later work years, and retirement years. The specific
      needs of the individual in each life era are examined and specific costs
      itemized. The provision of adequate services and supports affords tremendous
      opportunities and inclusion into the community.

PMID- 9661706
TI  - Locomoting through apertures of different width: a study of children with
      cerebral palsy.
AB  - Whether children with cerebral palsy (CP) differ from non-handicapped (NH)
      children was studied, using body-scaled information about the passability of a
      doorway-like opening. There were 55 children of whom 23 were NH and 32 had CP,
      the latter consisting of 12 who could stand and walk unaided (CP-Walk) and 20
      confined to a wheelchair (CP-Wheel). All groups were divided into two age ranges
      (5-8 and 9-13 year) and were tested on two occasions separated by an interval of
      12 months. On both occasions, testing involved three consecutive tasks: making
      perceptual (pre)judgments about the passability of an opening varying in width,
      actually attempting to locomote through the openings (performance), and another
      round of (post)judgments. Judgments and performance were expressed in terms of
      absolute and relative outcomes, the latter differing from the former in
      accounting for differences in body width relative to aperture width. There were
      two main findings. Firstly, the younger CP-Walk children were the least able to
      employ body-scaled information in judging aperture width and the older CP-Wheel
      and NH the most able. Secondly, when performances in passing through the openings
      were adjusted for differences in body width, all groups had similar outcomes.
      This findings lends credence to the notion that when action is used in the
      service of perception, this is beneficial for the visual-spatial abilities of
      both NH and CP children. The study concludes by pointing out future directions in
      this type of research as well as some of the clinical implications of the
      findings.

PMID- 9661707
TI  - Reliability of static standing balance in nondisabled children: comparison of two
      methods of measurement.
AB  - Static standing balance is commonly measured with research laboratory systems
      (LabSys) or clinical systems (ClinSys). The purposes of this study were to (1)
      assess the reliability of two systems designed to measure static standing balance
      in nondisabled children, (2) compare the findings derived from the two systems of
      measurement, and (3) examine the relationship between anthropometric measures and
      postural sway. Twenty-five nondisabled children (12 male, 13 female) ages 1 year
      11 months to 12 years 2 months (mean = 6 years 4 months; SD = 4 years 3 months)
      participated in the study. Each child stood on the LabSys and the ClinSys for
      three consecutive 10 second measurement periods. Intraclass correlation
      coefficients (ICC (2, 1)) for the three trials on each system were 0.62 (LabSys)
      and 0.63 (ClinSys). The level of agreement between the two systems was 0.61 (ICC
      (2, 1)). Younger children exhibited more variability and less agreement between
      measurement trials using the ClinSys. However, older children demonstrated more
      similar sway indices when comparing the two systems of measurement. Two-way
      analysis of variance indicated that there were significant differences between
      sway indices measured by the two systems (p < 0.01) and between the youngest
      children (aged 2-4 years) and all other children (p < 0.01). In addition,
      agreement among trials for the two systems was different depending on the age
      group measured. Correlation coefficients for sway index and age, height, weight,
      and foot length ranged from -0.52 to -0.64 for the LabSys (p < 0.01) and -0.62 to
      -0.73 for the Clin-Sys (p < 0.01). Stepwise multiple regression analysis
      indicated that height was the most significant predictor of sway when measured by
      the ClinSys (R2 = 0.536, p < 0.01) whereas age was the most significant predictor
      when sway was measured using the LabSys (R2 = 0.403, p < 0.01). The results
      suggest that the degree of postural sway and the reliability of the measurement
      itself are influenced by the age of the child and the measurement system
      employed.

PMID- 9661708
TI  - Video-based documentation and rating system of the motor behaviour of handicapped
      children treated with physiotherapy--a new outcome measure.
AB  - PURPOSE: Development of an instrument to measure modifications of motor quality
      in handicapped children receiving physiotherapy. METHODS: A video-based
      documentation method of motor behaviour in children from 0 to 3 years receiving
      physiotherapy was elaborated, consisting of a standardized set of scenes (script)
      and a rating procedure concerning different categories of motor behaviour such as
      coordination, stability and effort. RESULTS: The construction of the script and
      the rating system proved to be sensitive in documenting and evaluating the motor
      behaviour of handicapped children receiving physiotherapy. A good inter-rater
      reliability of 0.85 was obtained. The chosen rating categories represent two
      independent factors: One relating more to the motor functions (motor component)
      and the other relating to the psycho-social aspects of movement (interactive
      component). CONCLUSION: The instrument allows to evaluate the quality aspects of
      movement. They can be observed in motor behaviour regardless of which function is
      being executed and may develop in a different pace and at different stages of
      therapy than specific motor functions such as turning, sitting or walking. The
      instrument is intended to complement a standard neurological examination and the
      application of motor function tests, especially, to evaluate therapeutic
      outcomes.

PMID- 9661709
TI  - Cognitive rehabilitation therapy of brain-injured students in a public high
      school setting.
AB  - Cognitive rehabilitation therapy is a systematic effort to assist brain damaged
      individuals in developing ways to compensate for cognitive deficits. Although
      this treatment is considered standard in a field of rehabilitation, access to
      services is limited by the availability of specialists. A model for bringing
      cognitive rehabilitation techniques to children with acquired brain injury within
      their own school setting is presented. A convenience sample of 10 public high
      school students with acquired brain injury received biweekly cognitive
      rehabilitation sessions for 20 weeks. Treatment was based on a developmental
      model of brain functioning. Treatments were provided by trained school teachers
      under the supervision of psychologists specializing in cognitive rehabilitation.
      Students were evaluated pre- and post-treatment using neuropsychological tests.
      After treatment, the students demonstrated a significant increase in general
      memory ability (p < 0.05). These gains were due mostly to increases in verbal
      learning ability. Integration of cognitive rehabilitation therapy with public
      school services is a significant step in providing this valuable treatment to a
      wider range of children with acquired brain injury.

PMID- 9661710
TI  - Leukoencephalopathy after CNS prophylaxis for acute lymphoblastic leukaemia.
AB  - A 16 year old boy with epilepsy and learning difficulties is reported. At 3 years
      of age he was diagnosed with common acute lymphoblastic leukaemia, and received
      therapy according to the UK protocol, UKALL VIII. This included prophylactic CNS
      radiotherapy and chemotherapy. He did not develop CNS leukaemia, and complete
      remission was achieved. At age 7, he began to experience lethargy and learning
      difficulties, especially problems with hand-writing, concentration and memory.
      Furthermore, he began experiencing atypical absence seizures, which were provoked
      by concentration at times of tiredness. EEG showed bilateral non-specific
      abnormalities, with some epileptiform features. Over the following 9 years,
      several anti-epileptic drugs were prescribed. Although with the changes in
      therapy initial remissions have been achieved, the seizures have, each time,
      continued to relapse. At age 12, EEG was very abnormal, showing frequent
      generalized slow or sharp waves. At age 13, MRI revealed multiple discrete small
      high-intensity lesions in the subcortical white matter of both hemispheres.
      Problems with lethargy, concentration and memory persist and although multiple
      anti-epileptic drugs have been prescribed, seizures continue to occur almost
      daily.

PMID- 9661711
TI  - Specificity of treatment effects for learning disabilities in a boy prenatally
      exposed to dilantin.
AB  - The present case study provides evidence that a specific deficit can be improved
      by a treatment specific intervention in a boy who was prenatally exposed to
      Dilantin and presented with a learning disability. After implementation of a
      focused intervention for reading, standardized test scores revealed that the
      child demonstrated a dramatic improvement in reading performance, but remained
      consistent in other academic areas. This indicated that his reading improvement
      was the direct effect of specific training in reading, but did not generalize to
      other content areas. This finding is significant because it provides support for
      treatment specificity in contrast to treatment generalizability.

PMID- 9661712
TI  - Establishing the diagnostic validity of premenstrual dysphoric disorder using
      rasch analysis.
AB  - Premenstrual Dysphoric Disorder (PMDD) has remained in appendices of the last two
      editions of The Diagnostic and Statistical Manual of Mental Disorders due to lack
      of empirical study. Items included in its set of research criteria are considered
      tentative pending evidence of diagnostic validity. The present study attempts to
      establish the construct validity of the PMDD criteria using the Rasch method to
      analyze the validity of individual items as contributors to the diagnosis, in
      contrast to the usual but less precise approach of using an external validator to
      establish the diagnostic utility of psychiatric conditions. Analysis of which
      items best differentiate participants with and without PMDD provides an idea of
      the relative ability of these items to distinguish PMDD. It is recommended that
      the areas of anger/irritability, depressed mood, and problems in interpersonal
      functioning be expanded in further studies and corresponding items added to
      symptom checklists.

PMID- 9661713
TI  - Constructing rater and task banks for performance assessments.
AB  - The purpose of this paper is to present a set of procedures based on Rasch
      measurement theory for construction an assessment network. An assessment network
      is defined as a connected system of rater and task banks. Three general classes
      of data collection designs are presented that can be used to calibrate an
      assessment network; these are complete, incomplete, and non-linked assessment
      networks. Carefully constructed assessment networks based on Rasch measurement
      theory and sound data collection designs provide the opportunity to achieve
      objective and fair measurements.

PMID- 9661714
TI  - Development of a scale to assess concern about falling and applications to
      treatment programs.
AB  - This study used Rasch methodology to pursue three goals. First, we sought to
      demonstrate the psychometric limitations of the Falls Efficacy Scale (Tinetti,
      Richman, & Powell, 1990). Second, we addressed these limitations using a
      simultaneous calibration of the Falls Efficacy Scale and Mobility Efficacy Scale
      items. Third, we review previous explorations of the self-efficacy construct in
      relationship to health behaviors and discuss a possible treatment program based
      on the simultaneous calibrated items and Social Cognitive Theory. Results
      indicate that responses from the Falls Efficacy Scale fail to assess the higher
      ends of the self-efficacy continuum. Simultaneous calibration of items improved
      this lack of scale definition. This initial work in assessing self-efficacy
      perceptions provides a theoretical framework for planning treatment programs that
      may be more cost effective than collecting performance measures.

PMID- 9661715
TI  - Dimensionality of an early childhood scale using rasch analysis and confirmatory
      factor analysis.
AB  - This paper explores the use of Rasch analysis and linear confirmatory factor
      analysis as methods for investigating the dimensionality of an early childhood
      test (Gesell School Readiness Screening Test), taking into account the
      theoretical basis of test construction. The paper presents the results of
      empirical analyses using both approaches and discusses the theoretical and
      psychometric considerations that guide the selection and application of each
      technique.

PMID- 9661716
TI  - Physical disability construct convergence across instruments: towards a universal
      metric.
AB  - OBJECTIVES: This study examines the stability of a physical disability construct
      across instruments and samples. The purpose is not to report a formal equating of
      instrument calibrations, but to indicate whether such an effort would be likely
      to succeed. Theory. The economics transforming health care from its orientation
      toward crisis-driven disease reactions to population- and evidence-based
      preventive health management and individualized disease management demand general
      scale-free measures of functional independence. METHODS: A new method, pseudo
      common item equating, is demonstrated. Similar, but not identical items, from
      different instruments, calibrated on different samples, are compared. DATA: More
      than 30 articles presenting Rasch analyses of physical functioning scales were
      reviewed. Four instruments provided data from ten of these articles, for eleven
      different calibrations (two instruments are both included in one article).
      RESULTS: The final overall average correlation disattenuated for error is .93,
      with an average of 7 pseudo-common items, and an average p-value of .01, meaning
      that measures based on these calibrations should be linearly transformable
      versions of the same metric. Scientific importance. The quantitative stability of
      different areas of physical functional independence across instruments and
      samples suggests that the development and deployment of a universal metric is a
      realizable goal.

PMID- 9661717
TI  - Parameter recovery for the partial credit model using MULTILOG.
AB  - This study investigated parameter recovery for the partial credit model using the
      MULTILOG computer program. Factors studied were the sample size and the number of
      item parameters, which were manipulated by systematically varying the number of
      steps per item and the number of items. The findings suggest that the ratio of
      sample size to number of item parameters being estimated as a "rule of thumb" can
      be a more complete guideline when the number of steps per item is taken into
      account. Accurate estimation of ability can be obtained across all conditions,
      even with sample sizes as small as 250. With regard to estimation of step values,
      however, more caution is warranted. Accurate estimation of the step values of
      items which have more categories requires larger sample sizes for a given number
      of total parameters to be estimated.

PMID- 9661718
TI  - Objective measurement of figure skating performance.
AB  - Figure skating uses the median rank aggregation system for determining medal
      winners. Unfortunately, the system can be influenced by idiosyncratic ratings
      made by some judges unlike the skating ability measures from a many-facet Rasch
      analysis. These measures are constructed to be independent, as statistically
      possible, of item difficulties, judge severities, and the rating scale structure.
      A many-facet Rasch analysis was conducted on data from the controversial ladies
      event at the 1994 Olympics. The results illustrate how the idiosyncratic ratings
      of the judges were not accounted for by the median rank system, thus biasing the
      selection of the gold medal winner. All sports that rely on judges' ratings
      should investigate the use of a many-facet Rasch model in order to bring more
      objectivity and fairness to the winner selection process.

PMID- 9661719
TI  - Validating standard setting with a modified nedelsky procedure through common
      item test equating.
AB  - It is often impossible to validate cut scores set using judged item review
      methods due to the fact that many high stakes testing programs attempt to limit
      the number of common items across consecutively administered forms. However, over
      time, with a stable item pool, secondary links through other test administrations
      allow the use of common item equating to test the stability of the judged cut
      scores. In this study five forms of a basic science examination administered over
      a three year period in a national board testing program were analyzed to
      determine the stability of judged cut scores. The stability was determined by
      comparison of the judged cut scores with the equated cut scores derived by the
      Rasch common item equating technique. The results indicate cut scores derived
      from the modified Nedelsky procedure were within equating error of the Rasch
      equated cut scores over five administrations.

PMID- 9661720
TI  - On-line performance assessment using rating scales.
AB  - The purpose of this paper is to report on the development of the on-line
      performance assessment instrument--the Assessment of Motor and Process Skills
      (AMPS). Issues that will be addressed in the paper include: (a) the establishment
      of the scoring rubric and its implementation in an extended Rasch model, (b)
      training of raters, (c) validation of the scoring rubric and procedures for
      monitoring the internal consistency of raters, and (d) technological
      implementation of the assessment instrument in a computerized program.

PMID- 9661721
TI  - Evaluating the FONE FIM: Part I. Construct validity.
AB  - Rasch analysis was used in this paper to evaluate the Motor component of the FONE
      FIM, the telephone version of the Functional Independence Measure (FIM). For this
      purpose, 132 patients discharged from an inpatient geriatric assessment and
      rehabilitation program were assessed by trained research assistants using the
      FONE FIM. The results at 5 weeks post-discharge were compared to the observation
      FIMs (OBS FIMs) done at home 6 weeks post-discharge. These patients had an
      average age of 79 years and presented with multiple, complex medical problems and
      significant functional decline. The FONE FIM and the OBS FIM were shown to share
      a strikingly similar item hierarchy, based on Rasch item difficulty measures.
      Only bladder management and climbing stairs were misfitting items as indicated by
      item fit statistics. The same 13-item set and 4-point scales were shown to be
      psychometrically optimal for both the FONE FIM and the OBS FIM based on the
      person separation index. Further research is required to address the issue of the
      optimal item set and scale levels from psychometric and clinical perspectives.

PMID- 9661722
TI  - Scoring and analysis of performance examinations: a comparison of methods and
      interpretations.
AB  - The purpose of this study was to compare the results and interpretation of the
      data from a performance examination when four methods of analysis are used.
      Methods are 1) traditional summary statistics, 2) inter-judge correlations, 3)
      generalizability theory, and 4) the multi-facet Rasch model. Results indicated
      that similar sources of variance were identified using each method; however, the
      multi-facet Rasch model is the only method that linearized the scores and
      accounts for differences in the particular examination challenged by a candidate
      before ability estimates are calculated.

PMID- 9661723
TI  - Interpreting the chi-square statistics reported in the many-faceted Rasch model.
AB  - The different chi-square statistics reported in the many-faceted Rasch model
      analysis are presented and interpreted. In addition, other chi-square summary
      values are computed and presented for interpretation of facets. The chi-square
      values are useful for determining: (1) the significance of a facet in the Rasch
      model; (2) the significant contribution of facet main and interaction effects;
      (3) differences among facet elements; and (4) identifying the specific facet
      interaction adjustments to the subjects' calibrated logit ability measure.

PMID- 9661724
TI  - Evaluating the FONE FIM: Part II. Concurrent validity & influencing factors.
AB  - The "motor" (activities of daily living) component of the FONE FIM, the telephone
      version of the Functional Independence Measure (FIM) was evaluated in a cohort of
      132 patients who had been discharged to home from a geriatric inpatient
      assessment and rehabilitation program. In the current study, Rasch person ability
      measures were derived from telephone assessments 5 weeks after discharge and in
      home assessments 1 week later. Concordance between the modes was shown to be
      satisfactory for the Rasch measures based on intraclass correlation coefficients.
      However, the telephone mode consistently generated lower estimates than did the
      observational mode. This was due to the fact that the telephone mode
      underestimated motor function for the majority of patients who were at higher
      levels of cognition and motor function, but overestimated for patients who were
      at lower levels of cognition and motor function. At the item level, concordance,
      as determined by Kappa statistics, was better when the FONE FIM responses came
      from the patient rather than proxy respondents, and when the assessments were
      done by more experienced rather than less experienced raters. Based on these
      findings, a mixed strategy, the telephone mode for patients capable of responding
      to the FONE FIM and in-home assessments for those who are incapable, is
      recommended.

PMID- 9661725
TI  - Post-hoc Rasch analysis of optimal categorization of an ordered-response scale.
AB  - The purpose of this study was to determine the optimal categorization of a self
      efficacy ordered-response scale using the Rasch analysis and compare the
      performance of the Rasch statistics and parameter estimates with conventional
      statistics. A 50-item scale to measure psychomotor self-efficacy was administered
      to a total of 2,022 children, including 1,009 boys and 1,013 girls. The data
      analysis started by collapsing the original five adjacent categories into two,
      three, and four categories, and a total of 14 data sets were derived. Each of
      these data sets, including the original one, was analyzed using the Rasch rating
      scale model, and a set of Rasch model-data fit, category, and separation
      statistics and parameter estimates, as well as three conventional statistics,
      were computed and compared. It was found that, instead of the five-category
      construct designed, the best order of category meanings of the scale in
      respondents' perceptions was a three-category construct. The Rasch threshold
      estimates were sensitive indexes in determining the order of the categorization,
      and that item separation statistics were useful in determining the optimal
      categorization after its order was confirmed. The commonly used coefficient alpha
      was found not helpful at all in determining the optimal categorization. The Rasch
      analysis was demonstrated to be a useful post-hoc analytic approach in
      determining the optimal categorization of an ordered-response scale.

PMID- 9661726
TI  - The Sexual Experiences Survey: interpretation and validity.
AB  - The Sexual Experiences Survey (Koss, Gidycz, & Wisniewski, 1987) is a commonly
      used instrument for assessing various degrees of sexual aggression and
      victimization among male offenders and female victims. Rasch analysis was used to
      transform qualitative raw score observations into objective linear measures using
      the responses of a national sample of 6,159 higher education men and women across
      the United States, aged 18-24. This paper supports the construct validity of the
      survey through evaluation of the item hierarchy, fit statistics, and separation
      indices. Findings confirm a "dimensional" perspective on rape, suggesting that
      sexually aggressive behaviors can be scaled along a single continuum from normal
      to extreme sexual behavior. The item hierarchy reveals an arrangement of sexually
      aggressive acts in an order of mild to severe, which compares with the one
      theorized by the authors of the SES. Identity plots demonstrate the validity of
      using a common set of SES item calibrations to measure both male and female
      respondents. For interpretation of person responses to the SES, three conclusions
      are suggested. First, Rasch analysis must be employed to examine item responses
      effectively. Second, when the survey is administered to a college sample aged 18
      24, the item calibrations obtained in this paper can be used to measure offenders
      and victims. Third, a total raw score-to-measure conversion is not always
      sufficient to interpret person measures. Instead, a scalogram method needs be
      added to the Rasch analysis to separate the measures of offenders and victims who
      complete the survey. Implications for future research are discussed.

PMID- 9661727
TI  - Equating the MOS SF36 and the LSU HSI Physical Functioning Scales.
AB  - This study equates the physical functioning subscales of the Medical Outcomes
      Study Short Form 36 (SF36) and the Louisiana State University Health Status
      Instruments (LSU HSI). Data from the SF36's 10-item physical functioning scale,
      the PF10, and the LSU HSI's 29-item Physical Functioning Scale (PFS), were fit to
      separate and mixed Rasch rating scale models. Data were provided by a convenience
      sample of 285 patients waiting for appointments in a public hospital general
      medicine clinic. Difficulty estimates for a subset of similar items from the two
      instruments were highly correlated (.95), indicating that the items from the two
      scales are working together to measure the same variable. The measures from the
      two equated instruments correlate .80 (.86 when disattenuated for error). Of the
      two instruments, the PFS's error is lower, model fit is better, and reliability
      coefficients are higher. Both instruments measure physical functioning, and can
      do so in a common unit of measurement. Conversion tables are provided for
      transforming raw scores from either instrument into the common metric.

PMID- 9661728
TI  - The dimensionality and validity of the Older Americans Resources and Services
      (OARS) Activities of Daily Living (ADL) Scale.
AB  - The psychometric properties of the OARS ADL scale, comprised of seven physical
      activities of daily living (PADL) and seven instrumental activities of daily
      living (IADL) items, were examined using a Rasch measurement approach. Two of the
      PADL items failed to demonstrate acceptable goodness-of-fit with the measurement
      model but the remaining 12 items could be combined into a single measure of ADL
      ability. Although the OARS ADL scale was designed to identify those community
      dwelling elderly who need supports and services to continue to live in the
      community, the scale items were found to be poorly targeted to community-dwelling
      elderly since almost half of our sample received maximal scores. Rasch analysis
      identified how we might improve the sensitivity of the OARS ADL scale but its
      utility in outcome and longitudinal studies remains questionable.

PMID- 9661729
TI  - Man is the measure ... the measurer.
AB  - Measures originated from human anatomy. Metrology has moved from man the measure
      to man the measurer. This transformation is documented using examples taken from
      the history of metrology. The outcome measure are units constructed and
      maintained for their utility, constancy and generality.

PMID- 9661730
TI  - Evidence for the validity of a Rasch model technique for identifying differential
      item functioning.
AB  - This paper presents an analysis of differential item functioning (DIF) in a
      certification examination for a medical specialty. The groups analyzed were (1)
      physicians from different subspecialties within this area and (2) physicians who
      qualified for the examination through two different experiential pathways. The
      DIF analyses were performed using a simple Rasch model procedure. The results
      were shown to be readily interpretable in terms of the known differences between
      the groups being compared. These results serve as validity evidence for the Rasch
      model procedure as a means for evaluating DIF in examinations. The conclusion is
      drawn that complex procedures are not required to generate interpretable results
      if relevant differences between the groups being compared are known. This
      suggests that the inability of many researchers to interpret results for
      racial/ethnic or gender groups is not due to inadequacies of the methods, but
      more likely to lack of pertinent knowledge about group differences.

PMID- 9661731
TI  - Rasch analysis of distractors in multiple-choice items.
AB  - In order to apply the Rasch model to multiple-choice items, incorrect responses
      to distractors are usually aggregated to a single category. In doing so,
      information of individual distractors disappears. In this paper, a Rasch-type
      analysis is proposed where one parameter is assigned to each distractor. The
      information is thus preserved. The proposed distractor model can be applied to
      investigate the performance of distractors, which is useful for item revision.
      This model is a necessary condition of the Rasch model, that is, fitting the
      distractor model will fit the Rasch model, but not vice versa. The results of a
      small simulation study show that parameter recovery of the distractor model is
      very satisfactory. A real data set of twenty multiple-choice items was analyzed.
      Some items were found to fit the Rasch model rather than the distractor model. It
      is this diagnostic value that makes the distractor model suitable for multiple
      choice items.

PMID- 9661732
TI  - Using item mean squares to evaluate fit to the Rasch model.
AB  - Throughout the mid to late 1970's considerable research was conducted on the
      properties of Rasch fit mean squares. This work culminated in a variety of
      transformations to convert the mean squares into approximate t-statistics. This
      work was primarily motivated by the influence sample size has on the magnitude of
      the mean squares and the desire to have a single critical value that can
      generally be applied to most cases. In the late 1980's and the early 1990's the
      trend seems to have reversed, with numerous researchers using the untransformed
      fit mean squares as a means of testing fit to the Rasch measurement models. The
      principal motivation is cited as the influence sample size has on the sensitivity
      of the t-converted mean squares. The purpose of this paper is to present the
      historical development of these fit indices and the various transformations and
      to examine the impact of sample size on both the fit mean squares and the t
      transformations of those mean squares. Because the sample size problem has little
      influence on the person mean square problem, due to the relatively short length
      (100 items or less), this paper focuses on the item fit mean squares, where it is
      common to find the statistics used with sample sizes ranging from 30 to 10,000.

PMID- 9661733
TI  - The functional assessment measure (FAM) in closed traumatic brain injury
      outpatients: a Rasch-based psychometric study.
AB  - The Functional Assessment Measure (FAM) has been proposed as a measure of
      disability in post-acute Traumatic Brain Injury (TBI) outpatients. It is
      comprised of the 18 items of The Functional Independence Measure (FIMSM), scored
      in terms of dependence, and of 12 newly designed items, scored in terms of
      dependence (7 items) or performance (5 items). The FIMSM covers the domains of
      self-care, sphincter management, mobility, locomotion, communication and social
      cognition. The 12 new items explore the domains of community integration,
      emotional status, orientation, attention, reading/writing skills, swallowing and
      speech intelligibility. By addressing a set of problems quite specific for TBI
      outpatients the FAM was intended to raise the ceiling of the FIMSM and to allow a
      more precise estimate of their disability. These claims, however, were never
      supported in previous studies. We administered the FAM to 60 TBI outpatient, 2-88
      months (median 16) from trauma. Rasch analysis (rating scale model) was adopted
      to test the psychometric properties of the scale. The FAM was reliable (Rasch
      item and person reliability 0.91 and 0.93, respectively). Two of the 12 FAM
      specific items were severely misfitting with the general construct, and were
      deleted. Within the 28-item refined FAM scale, 4 new items and 2 FIMSM items
      still retained signs of misfit. The FAM was on average too easy. The most
      difficult item (a new one, Employability) did not attain the average ability of
      the subjects. Also, it was only slightly more difficult than than the most
      difficult FIMSM item (Memory). The FAM does not seem to improve the FIMSM as a
      far as TBI outpatients are to be assessed.

PMID- 9661734
TI  - The effect of item pool restriction on the precision of ability measurement for a
      Rasch-based CAT: comparisons to traditional fixed length examinations.
AB  - This paper describes a method for examining the precision of a computerized
      adaptive test with a limited item pool. Standard errors of measurement
      ascertained in the testing of simulees with a CAT using a restricted pool were
      compared to the results obtained in a live paper-and-pencil achievement testing
      of 4494 nursing students on four versions of an examination of calculations of
      drug administration. CAT measures of precision were considered when the simulated
      examine pools were uniform and normal. Precision indices were also considered in
      terms of the number of CAT items required to reach the precision of the
      traditional tests. Results suggest that regardless of the size of the item pool,
      CAT provides greater precision in measurement with a smaller number of items
      administered even when the choice of items is limited but fails to achieve
      equiprecision along the entire ability continuum.

PMID- 9661735
TI  - Controlling the judge variable in grading essay-type items: an application of
      Rasch analyses to the recruitment exam for Korean public school teachers.
AB  - The purpose of this paper is to show how the Rasch measurement model can be used
      to control the effects of judge variable on the grading of essay-type items in
      the recruitment test for Korean teachers. Special attention is given to two
      aspects of judges' involvement in the grading. One is to identify a way to
      minimize the variation of grading due to judge severity. The other concern is to
      figure out a way to reduce the number of judges without threatening objectivity
      of ability estimates. Results from the FACETS analyses tell us not only how much
      grading standards vary among judges and how to adjust them but also it produces
      comparably reliable ability estimates with fewer judges.

PMID- 9661736
TI  - Team assessment utilizing a many-facet Rasch model.
AB  - As organizations begin to implement work teams, their assessment will ultimately
      reflect compensation strategies that move away from individual assessment. This
      will involve not only using multiple raters, but also the use of multiple
      criteria. Team assessment using multiple raters and multiple criteria is
      therefore necessitated; however, this can produce differences in ratings due to
      the leniency or severity of the individual team raters. This study analyzed the
      ratings of individual members on 31 different teams across 12 different criteria
      of team performance. Utilizing the many-facet Rasch model, statistical
      differences between the teams and 12 criteria were calculated.

PMID- 9661737
TI  - Round-off error, blind faith, and the powers that be: a caution on numerical
      error in coefficients for polynomial curves fit to psychophysical data.
AB  - Graphing and statistics software often permits users to fit polynomial curves,
      like a parabola or sigmoid, to scatter plots of psychophysical data points. These
      programs typically calculate the curve using double- or extended-precision
      numerical algorithms and display the resulting curve overlaid graphically on the
      scatter plot, but they may simultaneously display the equation that generates
      that curve with numerical coefficients that have been rounded off to only a few
      decimal places. If this equation is used for experimental or clinical
      applications, the round-off error, especially on coefficients for the higher
      powers, can produce anomalous findings due to systematic and extreme distortions
      of the fitted curve, even artifactually reversing the algebraic sign of the true
      slope of the fitted curve at particular data points. Care must be exercised in
      setting round-off criteria for coefficients of polynomial terms in curve-fit
      equations to avoid nonsensical measurement and prediction.

PMID- 9661738
TI  - Transdifferentiation of chick embryonic retinal pigment epithelial cells to
      lentoid structure in suspension culture.
AB  - To test transdifferentiation of retinal pigment epithelial (RPE) cells in
      suspension culture, chick embryonic RPE sheets and dissociated RPE cells were
      cultured for two months in a non-adherent dish for suspension culture. RPE cells,
      isolated as a sheet, aggregated immediately and remained the same size with their
      differentiated characteristics for two months. The presence of basic fibroblast
      growth factor (bFGF) at concentrations of 10 ng/ml or higher induced the
      formation of a spherical lentoid structure which was positive for crystallin and
      bFGF receptor. In contrast, dissociated RPE cells did reaggregate but did not
      develop the lentoid structure even in the presence of bFGF. The
      transdifferentiation of RPE cells to the lentoid structure in this study was in
      contrast to their transdifferentiation to the retina, as reported in a previous
      study.

PMID- 9661739
TI  - Experimental study of partial liquid ventilation in the setting of acute
      respiratory failure induced by sea water lung lavage in rabbits.
AB  - To study the effect of partial liquid ventilation (PLV) with perfluorocarbon on
      acute respiratory failure, 3 groups of 17 rabbits were examined to compare. After
      acute respiratory failure was induced by lung lavage with sea water in 12 of the
      17 rabbits, 7 of the 12 rabbits were treated with conventional mechanical
      ventilation (AC group) and 5 of the 12 rabbits were treated with PLV using
      perfluorocarbon (AP group). The remaining 5 normal rabbits without acute
      respiratory failure were treated with PLV with perfluorocarbon as a control group
      (PL group). In the PL group, PaO2, PaCO2, blood pH, pulmonary compliance or
      pathological findings were not so changed after PLV. In the AC and AP groups,
      PaCO2 significantly increased, and in contrast, PaO2 and pulmonary compliance
      significantly decreased after lung lavage. However, these findings improved to
      almost the same levels as those of a control group within 2 h after the PLV
      treatment in the AP group, but in the AC group, these gradually deteriorated over
      time. As for the pathological findings, pulmonary vascular congestion, alveolar
      hemorrhage and inflammatory infiltration were observed in the AC group. However,
      these findings were not observed in the specimens of the AP group. From these
      results, PLV with perfluorocarbon was shown to be useful to improve gas exchange
      and pulmonary functions without major side effects.

PMID- 9661740
TI  - Steady-state serum concentrations of carbamazepine and valproic acid in obese and
      lean patients with epilepsy.
AB  - Steady-state serum concentrations of carbamazepine (CBZ) and valproic acid (VPA)
      were investigated in normal weight (body mass index; BMI 20 to 25), lean (smaller
      than 20 BMI) and moderately obese subjects (greater than 25 BMI) who received
      either 400 mg/day of CBZ or 800 mg/day of VPA. The CBZ serum concentration in
      lean subjects was significantly higher than that in normal weight subjects.
      However, no significant differences in VPA serum concentration were found between
      the three groups. The CBZ serum concentration decreased with increases in total
      body weight, and the VPA serum concentration decreased with increases in ideal
      body weight. However, both serum concentrations were not correlated with BMI.
      These results suggest that VPA doses should be calculated using ideal body weight
      and that degree of obesity may affect CBZ serum concentration rather than VPA
      serum concentration.

PMID- 9661741
TI  - Wider distribution of salivary-type isoamylase activity as compared with
      pancreatic-type isoamylase activity in serum: a study on young female adults.
AB  - The clinical implications of a wider distribution of salivary type (S-type)
      isoamylase activity, as compared with that of pancreatic type (P-type) isoamylase
      activity in the serum of young female adults of 18-23 years old was studied. A
      high correlation existed between the S-type isoamylase levels in the initial
      determination and those in the second determination one year after on the same
      subjects, indicating that the wider distribution of S-type isoamylase level
      reflects an individual variation. The serum level of S-type isoamylase was highly
      correlated with the S-type isoamylase activity in saliva. Among the additional
      factors studied, a weak positive correlation was present between energy intake
      and the total and S-type isoamylase activities in serum. However, there was no
      negative correlation between the S-type isoamylase level and body mass index
      (BMI), which was reported for young male adults.

PMID- 9661742
TI  - Serum alpha-fetoprotein levels in healthy Japanese adults.
AB  - With advances in lectin affinity electrophoresis of alpha-fetoprotein (AFP), the
      detection of significant changes in serum AFP at low levels in cirrhotics has
      become important for early detection of hepatocellular carcinoma. Serum AFP
      levels of 616 healthy individuals without abnormal liver function tests or virus
      markers of hepatitis B and C were determined by enzyme immunoassay with IMx-AFP
      Dainapack using automated IMx apparatus set at twice the ordinary sensitivity and
      compared with those of 241 individuals with abnormal liver function tests and/or
      positive hepatitis virus markers. The coefficient of variation in this assay was
      less than 10% at AFP levels as low as 0.2 ng/ml with a lower detection limit of
      0.1 ng/ml. The AFP level of healthy population showed a Gaussian distribution
      curve after logarithmic transformation with a median and 2.5-97.5 percentile
      reference range of 2.2 (0.6-5.6) ng/ml. There was no significant difference in
      the AFP level between males and females. Individuals with abnormal liver function
      tests alone showed no significant increase in serum AFP unless they were
      associated with positive hepatitis virus markers.

PMID- 9661743
TI  - Evaluation of the thigh muscles after knee exercise on a Cybex II.
AB  - We investigated the degree of local heat and swelling of the thigh muscles
      produced by exercise. Eleven university athletes aged from 19 to 23 years old
      performed isokinetic exercise of the right knee on a Cybex II. Then serial
      determination of thigh circumference and thigh temperature (up to 120 min after
      exercise) as well as serial magnetic resonance (MR) imaging (up to 60 min after
      exercise) was performed on both thighs. The circumference of the right thigh
      peaked at 5.6 +/- 2.1 min after exercise and returned to normal at 38.6 +/- 9.2
      min. The temperature of the right thigh peaked at 14.2 +/- 5.7 min after exercise
      and was not normalized after 120 min except in two subjects. T2-weighted MR
      images showed a marked increase in the signal intensity of the right knee flexor
      and extensor muscles. The signal intensity peaked immediately after exercise and
      subsequently decreased gradually but did not return to normal after 60 min in
      some muscles. Changes in the thigh circumference were closely correlated with
      changes in the MR findings. The changes in the thigh muscles after knee exercise
      could be demonstrated using MR imaging, thigh circumference, and thigh
      temperature data. These parameters may provide indicators for managing muscle
      fatigue and recovery.

PMID- 9661744
TI  - Risk analysis of the exposure to GB virus C/hepatitis G virus among populations
      of intravenous drug users, commercial sex workers and male outpatients at STD
      clinic in Chiang Mai, Thailand: a cross-sectional case-control study.
AB  - An exposure to GB virus C/hepatitis G virus (GBV-C/HGV) was studied among
      populations at risk for blood and sexual exposure to analyze risk factor of the
      transmission of the virus. Blood samples were drawn from 98 intravenous drug
      users (IVDU), 100 female high-class commercial sex workers (CSW) and 50 male
      outpatients (MOP) at a sexually transmitted diseases (STD) clinic in Chiang Mai,
      Thailand. These blood samples were analyzed for GBV-C/HGV RNA; antibodies against
      second envelope protein of GBV-C/HGV (anti-E2); anti-hepatitis C virus antibody
      (HCV-Ab); hepatitis B core antibody (HBcAb); and antibodies against human
      immunodeficiency virus (HIV-Ab). Prevalences of GBV-C/HGV RNA, anti-E2, HCV-Ab,
      HBcAb and HIV-Ab were 27.6%, 16.3%, 84.7%, 76.5% and 45.0% in IVDU; 0%, 21.5%,
      2.0%, 72.0% and 11.0% in CSW; 6.0%, 13.6%, 0%, 64.0% and 14.0% in MOP. While the
      prevalence of GBV-C/HGV RNA was higher in IVDU than in CSW and MOP, comparable
      prevalences of anti-E2 among the three populations were found. Intravenous drug
      injection showed association with GBV-C/HGV RNA, while history of STD associated
      with anti-E2. In conclusion, intravenous drug injection and STD were found to be
      risk factors for the previous exposure to GBV-C/HGV, but STD did not increase the
      risk of the GBV-C/HGV viraemia.

PMID- 9661746
TI  - European academy of otology and neurotology.

PMID- 9661745
TI  - Repeated mazindol and methamphetamine administration produces cross-sensitization
      to stereotyped behavior induced by these agents in rats.
AB  - The cross-sensitization to stereotyped behavior between mazindol (MZD) and
      methamphetamine (MAP) was investigated in rats. MZD (5 and 10 mg/kg/day, p.o.),
      MAP (5 and 10 mg/kg/day, p.o.) and saline (1 ml/kg, p.o.) were administered once
      daily for a week. Challenge with MZD (10 mg/kg, p.o.) on the 8th day caused
      markedly stereotyped behavior in MAP-pretreated group compared with the saline
      pretreated control group. MAP (10 mg/kg, p.o.)-induced stereotyped behavior on
      the 8th day was also greater in MZD-pretreated group rather than the saline
      pretreated control group. These results suggest that repeated MZD and MAP
      administration cross-sensitizes to their stereotype-producing effects.

PMID- 9661747
TI  - Lateral and anterior view to tensor fold and supratubal recess.
AB  - HYPOTHESIS: The aim of this study was to find suitable methods for basic anatomic
      evaluation of the supratubal recess and the anterior surface of the tensor fold.
      BACKGROUND: The current method of superior microdissection via the middle fossa
      floor provides a good picture of the anatomy and pathology of the epitympanum,
      but the supratubal recess can be evaluated only after excision of the tensor
      fold. Postinflammation changes cannot be examined accurately because destruction
      of the tensor fold necessarily alters the anatomic details. METHODS: Eight
      temporal bones were studied via a lateral and 14 via an anterior approach, both
      complemented by the superior microdissection. Data on 51 earlier superior
      dissections were reevaluated as to the state of the supratubal recess. Histology
      was documented from eight biopsy specimens and of four serially sectioned
      temporal bones, two normal and two infected. RESULTS: The lateral route offered a
      good view to the tensor tendon and lower portion of the tensor fold, but the
      anterior malleal ligament obstructed the view to the fold's upper portion. The
      anterior route offered excellent visibility to the anterior pouch, mesotympanum,
      tensor fold, and the whole supratubal recess. The tensor fold was mostly fixed
      superiorly to the bony roof with a narrow or broad soft band of composite tissue,
      infrequently to the transverse crest directly. Inflammatory changes spread from
      the tympanic isthmus region to the supratubal space over the fold and, if
      extensive, formed broad inflammatory and scar tissue bands between the fold and
      the anterior bony wall. CONCLUSIONS: The supratubal recess and the mesotympanum
      can best be evaluated via the anterior approach, which should be added to the
      temporal bone microdissection program. It serves well as the starting route,
      followed by the conventional superior dissection of the epitympanum. The
      knowledge gained is indispensable in surgery for chronic otitis media for
      creation of a large common middle ear air space and functioning aeration
      pathways.

PMID- 9661748
TI  - Reversible canal wall down tympanomastoidectomy. An alternative to intact canal
      wall and canal wall down mastoidectomy procedures.
AB  - OBJECTIVE: To avoid the limitations of canal wall down surgery yet maintain the
      exposure provided by canal wall down mastoidectomy, the authors have developed a
      completely "reversible" canal wall down mastoidectomy technique. The purpose of
      this case report is to determine the feasibility of the "reversible" canal wall
      down mastoidectomy technique in the treatment of a patient with an aural
      cholesteatoma. STUDY DESIGN: Having refined the surgical technique using cadaver
      temporal bones, the "reversible" canal wall down mastoidectomy was performed in a
      patient with a recurrent aural cholesteatoma. SETTING: The surgical technique was
      refined in the Carolina Ear Research Institute's temporal bone dissection lab.
      The patient underwent the surgical procedure by JTM in a standard operating room
      setting at a private hospital in Raleigh, North Carolina. PATIENTS: The patient
      was a private patient, referred to the Carolina Ear & Hearing Clinic for
      treatment of recurrent cholesteatoma. INTERVENTION: A "reversible" canal wall
      down mastoidectomy was performed in this patient. MAIN OUTCOME MEASURES: The
      surgeon determined the adequacy of cholesteatoma exposure following temporary
      removal of the posterior bony canal wall. Intra-operatively, the surgeon assessed
      the repositioned posterior bony canal segment, looking specifically at its
      stability and the absence of gaps along the canal cuts. RESULTS: Temporary
      removal of the posterior bony canal wall improved exposure of the cholesteatoma
      and facilitated cholesteatoma removal. The repositioned bony canal segment was
      well stabilized by the bone cement (Oto-cem) and no gaps were noted along the
      canal cuts. CONCLUSION: Although it is premature to compare the effectiveness of
      the "reversible" canal wall down technique to other mastoidectomy procedures,
      this case confirms the feasibility of this approach.

PMID- 9661749
TI  - The use of vascular flaps in middle ear surgery.
AB  - OBJECTIVE: This study aimed to evaluate improved surgical outcomes from middle
      and external ear surgery using local vascular flaps to enhance tissue healing.
      STUDY DESIGN: The study design was a review of the design and clinical trials of
      three soft tissue flaps: the middle temporal flap (MTF), the middle temporal
      canal flap (MTCF), and the wing flap. All derive axial vascular supply from the
      middle temporal vessels. SETTING: The study was performed at a single surgeon's
      private otologic practice. PATIENTS: A total of 319 patients were treated from
      1991-1996: MTF in 223, MTCF in 38, and wing flap in 58. The average case maturity
      was 2.25 years. Most cases were mastoidectomy reconstruction or intact canal wall
      mastoidectomy. INTERVENTION: The flaps are used to introduce an improved blood
      supply to key repair sites in the middle and external ear. MAIN OUTCOME MEASURES:
      Canal skin breakdown, chronic myringitis, and chronic otitis externa were
      measured. RESULTS: Dehiscence rates fell from 15-5% and myringitis rates fell
      from 15-4%. Thicker, vascular canal skin was the usual result. CONCLUSIONS: The
      flaps provide the optimal method of revascularizing the external canal during
      mastoidectomy reconstructions and possibly canal defect repairs during intact
      canal wall mastoidectomy. Further studies are required to evaluate the efficacy
      of the wing flap and the MTCF.

PMID- 9661750
TI  - Growth factors in tympanic membrane perforations.
AB  - OBJECTIVE: Little is known about the arrested healing of chronic central tympanic
      membrane perforations and the mechanism involved in this process. Some authors
      have traced the failure to a growth factor deficiency at the perforation margin.
      In addition, recently, several growth factors have been tried out to improve
      tympanic membrane (TM) closure in animals. The authors sought to determine the
      expression of some well-known growth factor peptides in normal human TM and in
      TMs with a chronic central perforation. MATERIALS AND METHODS: Total TM specimens
      were obtained from patients with a normal TM (N = 10) soon after death and from
      patients with a chronic perforation (N = 20) undergoing myringoplasty with use of
      an allograft TM. Formaldehyde solution-fixed TMs were analyzed after
      immunohistochemical staining using highly purified monoclonal antibodies to
      determine whether epidermal growth factor receptor (EGF-r), transforming growth
      factor-alpha (TGF-alpha), basic fibroblast growth factor (b-FGF), or transforming
      growth factor-beta 1 (TGF-beta 1) was expressed in the TMs. RESULTS: The
      distribution pattern for EGF-r, TGF-alpha, and b-FGF was similar in perforated
      and nonperforated TMs. In contrast to this, TGF-beta 1 staining was markedly
      different in perforated and nonperforated TMs. No or minimal TGF-beta 1 was
      observed in normal TMs, whereas TGF-beta 1 staining was prominent in perforated
      membranes, mostly at the perforation border. CONCLUSIONS: The authors
      experimental findings imply that EGF-r, b-FGF, and TGF-alpha expression are not
      significantly different in TMs with and without a central chronic perforation.
      However, for TGF-beta 1, the authors found an increased staining pattern in
      perforated TMs when compared with that of normal TMs, and staining at the
      fibrotic and scarred perforation margin was pronounced. Based on these findings,
      the authors speculate on the possible role of TGF-beta 1 in the development of
      the fibrotic scar at the perforation margin explaining the deficient healing
      pattern of tympanic membranes in chronic otitis media. Possible clinical
      implications for the future, including growth factor therapy, are discussed.

PMID- 9661751
TI  - Intratympanic gentamicin injection for the treatment of Meniere's disease.
AB  - OBJECTIVE: This study aimed to examine the effectiveness of intratympanic
      injection of gentamicin as a nonsurgical treatment option in the treatment of
      patients with unilateral Meniere's disease who are refractory to medical
      treatment. STUDY DESIGN: The study design was a prospective case series. SETTING:
      The study was conducted at a physician's office setting in a tertiary care
      hospital. PATIENTS: The results of 37 patients who became eligible for reporting
      according to the American Academy of Otolaryngology Head and Neck Surgery (AAO
      HNS) guidelines for reporting treatment results of Meniere's disease were
      reviewed. INTERVENTION: Intratympanic injections of a prepared gentamicin
      concentration of approximately 30 mg/ml were given weekly until the patient
      reported cessation of vertigo attacks. Patients reclined for 45 minutes after
      each injection. MAIN OUTCOME MEASURES: The 1995 AAO-HNS guidelines were used in
      this report, and measures included pure-tone hearing results, word recognition
      scores, vertigo control scores, and ice-water calories after a minimum of 24
      months of follow-up. RESULTS: Vertigo control was achieved in 32 patients (87%).
      Fifteen patients (41%) had complete recovery from vertigo spells, 17 patients
      (46%) had substantial recovery, and 5 patients (14%) had treatment failure
      requiring additional surgery to control vertigo. Hearing results showed that 21
      patients (72%) had unchanged or better hearing, 10 patients (28%) had an average
      threshold shift of 10-25 dB, 4 patients (11%) had a threshold shift between 16
      and 25 dB, 1 patient (3%) had a threshold shift between 26 and 40 dB, and 1
      patient (3%) had a threshold shift of > 40 dB. CONCLUSIONS: The authors found
      intratympanic gentamicin to be a useful alternative to surgery. The flexible
      treatment protocol allowed for better hearing monitoring compared to the more
      frequent injection schedules of other studies and yielded a lower rate of severe
      hearing loss. It had a higher failure rate for vertigo control and a greater
      amount of hearing loss than the author's experience with vestibular nerve
      section.

PMID- 9661752
TI  - Early post-laser stapedotomy hearing thresholds.
AB  - OBJECTIVE: Auditory testing is not routinely performed within 4-6 weeks after
      stapedotomy, because hearing acuity is thought to be transiently depressed. In
      rare circumstances, postsurgical auditory and vestibular complaints may lead one
      to test hearing soon after stapedotomy. The early postoperative effects of carbon
      dioxide (CO2) and potassium titanyl phosphate (KTP) lasers, which now are
      routinely used to perform stapedotomies, have not been reported. The purpose of
      this report is to present normative data for auditory thresholds measured within
      2 weeks of laser stapedotomy. STUDY DESIGN: The study design was a prospective,
      unblinded study. SETTING: The study was conducted at three academic medical
      centers. PATIENTS: Thirty-six subjects undergoing 38 stapedotomies for
      otosclerosis by 5 surgeons participated. MAIN OUTCOME MEASURES: Behavioral
      audiometry was performed using standard techniques beginning before surgery and
      continuing through > 1 year after surgery. RESULTS: The CO2 laser was used in 26
      stapedotomies and the KTP laser was used in 12. Nine cases were revision
      procedures. Bone conduction pure-tone averages and speech discrimination scores
      did not worsen during the early postoperative period. Bone conduction at 250 and
      4,000 Hz dropped slightly within the first 2 weeks (-4.3 and -6.7 dB) but
      recovered thereafter. Bone conduction at 1,000 Hz actually improved within the
      first week after surgery (+6.2 dB, p = 0.021). Significant improvements in air
      conduction thresholds (and air-bone gap) were seen at the second week and late
      audiometry. The results for CO2 and KTP laser-treated groups were not
      significantly different. CONCLUSIONS: Cochlear function is not significantly
      depressed in the early postoperative period after laser (CO2 or KTP) stapedotomy.

PMID- 9661753
TI  - The etiology of idiopathic sudden sensorineural hearing loss. Experimental herpes
      simplex virus infection of the inner ear.
AB  - HYPOTHESIS: Experimentally induced herpes simplex virus type 1 (HSV-1)
      labyrinthitis provides a suitable model for idiopathic sudden sensorineural
      hearing loss (ISSHL). BACKGROUND: Viral labyrinthitis has been postulated to play
      a role in the pathophysiology of ISSHL. Circumstantial evidence is pointing at
      members of the herpes virus family. Experimental viral labyrinthitis elicited by
      various virus families leaves a virus-specific pattern of cochlear damage. Herpes
      viruses provide the best matching pattern in the distribution of cochlear damage
      when compared with ISSHL postmortem cochlear histopathology. METHODS: Herpetic
      viral labyrinthitis was induced in guinea pigs using perilymphatic inoculation
      with HSV-1. A control group was inoculated with the culture medium only.
      Infection was confirmed by the measurement of HSV antibodies. Hearing was
      monitored. Cochlear damage was evaluated by light and electron microscopy.
      RESULTS: In all HSV-1 inoculated animals, rapid loss of hearing occurred.
      Seroconversion took place, but no systemic manifestations of herpetic infection
      were observed. The control group showed no cochlear or systemic symptoms. When
      comparing cochlear histopathology in ISSHL to experimental viral HSV-1
      labyrinthitis, strong similarities were found: degeneration of the stria
      vascularis, destruction of the organ of Corti, loosening of the tectorial
      membrane, and inflammatory changes in neural structures. CONCLUSIONS: Based on
      clinical and histopathologic characteristics, experimental HSV-1 labyrinthitis
      provides a suitable model of ISSHL.

PMID- 9661754
TI  - Communication outcomes related to early implantation.
AB  - OBJECTIVE: This study aimed to document the communicative outcomes of early
      implantation. HYPOTHESIS: It is hypothesized that by implanting children between
      the ages of 2 and 5 years, it would be possible to capitalize on the critical
      period of language learning that occurs in the preschool years and thus
      positively effect communicative outcomes. STUDY DESIGN: Thirty-three children who
      were between 2 and 5 years at the time of implantation were followed
      longitudinally. They were administered a battery of speech perception (closed and
      open set), speech production, and oral language (vocabulary and syntax) tests at
      five test intervals across a 3-year span. RESULTS: Open-set speech perception was
      attained by 24 months with mean scores of 70% correct phonemes by the end of year
      3. Speech production improved to mean scores of 90% for suprasegmental features
      and 88% and 69% for vowels and consonants, respectively, by 3 years postimplant.
      These children made 33 months' gain in receptive vocabulary and 48 months' gain
      in expressive vocabulary in 36 months' time. Syntactically, they progressed from
      simple vocalization to simple sentences with some grammatical elements present.
      Repeated measures analysis of variance showed no significant differences between
      the subjects implanted between 2 and 3 years of age and those implanted between 3
      and 5 years of age at any period. Within groups, the scores obtained for each
      test period were significantly different from each other. CONCLUSIONS: Rapid
      improvement was noted in speech production and language acquisition after
      improved speech perception for these children implanted before 5 years of age, at
      levels that exceed those reported in the literature for children implanted at
      older ages.

PMID- 9661755
TI  - Single-channel to multichannel conversions in adult cochlear implant subjects.
AB  - OBJECTIVE: This study aimed to compare open-set speech perception of single
      channel with multichannel cochlear implants in the same ear of postlingually
      deafened adults. STUDY DESIGN: The study design was a retrospective case and
      literature review. SETTING: The study was conducted at a tertiary referral center
      with an associated veterans administration hospital. PATIENTS: Postlingually
      deafened adults with at least 6 months of experience with a single-channel
      cochlear implant were studied. INTERVENTION: Replacement of a single-channel with
      a multichannel cochlear implant in the same ear was performed. MAIN OUTCOME
      MEASURES: Open-set word and sentence perception scores at least 6 months after
      single-channel implantation and multichannel reimplantation were measured.
      RESULTS: Six of six patients had substantial improvement in open-set speech
      recognition after reimplantation of the same ear. CONCLUSIONS: Removal of a
      functioning single-channel implant and replacement with a multichannel device are
      appropriate in postlingually deafened adults who desire better speech
      recognition.

PMID- 9661756
TI  - Somatosensory phenomena after multichannel cochlear implantation in prelingually
      deaf adults.
AB  - OBJECTIVES: Central auditory system development in thought to be dependent on
      normal auditory nerve excitation. Central auditory disorganization may differ
      between prelingual and postlingual deafness. One possible clinical manifestation
      of such central auditory disorganization is somatosensory perception with
      cochlear implant stimulation. The purpose of this study was to investigate the
      incidence and characteristics of somatosensory phenomena in prelingually and
      postlingually deafened adult cochlear implant subjects. STUDY DESIGN: The study
      design was a retrospective analysis. SETTING: The study was performed at an
      academic tertiary referral center. PATIENTS: This study included 32 adult
      multichannel cochlear implant recipients. MAIN OUTCOME MEASURES: Subjective
      patient reporting of sensory perception after cochlear implant stimulation was
      reviewed. RESULTS: All 10 prelingually deaf subjects noted somatosensory
      phenomena distant from the implanted ear (e.g., chest, abdomen) on implant
      stimulation. These sensations resolved gradually for all patients. No subject
      deafened after the age of 2 years reported somatosensory perceptions.
      CONCLUSIONS: Somatosensory phenomena experienced by prelingually deafened adults
      suggest that disorganization of central auditory system pathways is more severe
      in these individuals. Earlier auditory deprivation appears to produce greater
      central auditory alterations, and perceptible crossover between somatosensory and
      auditory signals may be the end result.

PMID- 9661757
TI  - Pulsatile tinnitus. A 15-year experience.
AB  - PURPOSE: This study aimed to report the author's 15-year experience with the
      systematic evaluation and treatment of patients with pulsatile tinnitus. METHODS:
      Between August 1981 and August 1996, 145 patients with pulsatile tinnitus were
      evaluated. The diagnostic protocol was individualized according to the clinical
      findings and included appropriate radiologic testing, ultrasonography studies,
      and lumbar puncture with cerebrospinal fluid pressure measurement. Treatment was
      directed toward the etiology of the tinnitus. RESULTS: Benign intracranial
      hypertension syndrome (pseudotumor cerebri) was the most common diagnosis (56
      patients), followed by atherosclerotic carotid artery disease (24 patients) and
      glomus tumors (17 patients). In 13 patients, no specific diagnosis could be
      reached. CONCLUSIONS: Thorough history and physical examination are the two most
      important factors in evaluating patients with pulsatile tinnitus. Evaluation
      should be individualized and may include radiologic testing, ultrasonography
      studies, and lumbar puncture with cerebrospinal fluid pressure measurements. The
      majority of patients have a treatable underlying etiology.

PMID- 9661758
TI  - Summating potential and action potential ratio in Meniere's disease before and
      after treatment.
AB  - OBJECTIVE: This study aimed to compare the summating potential and action
      potential ratio (SP:AP) in patients with Meniere's disease before and after
      various surgical and medical treatments as an indication of change in
      endolymphatic hydrops to study the progression of Meniere's disease. STUDY
      DESIGN: The study design was a retrospective case review. SETTING: The study was
      conducted at an otology-neurotology referral center. PATIENTS: Eighty-eight ears
      of 84 patients with Meniere's disease received medical treatment in 18 ears and
      surgical treatments including endolymphatic shunt in 12 ears, streptomycin
      perfusion of the lateral semicircular canal in 9 ears, streptomycin perfusion of
      the middle ear in 33 ears, and dexamethasone perfusion of the middle ear in 16
      ears. INTERVENTION: Transtympanic electrocochleography (ECoG) was performed in
      all patients before treatment and 1-57 months after treatment (mean, 13.5 months)
      with a 2-year interval in 28 patients. MAIN OUTCOME MEASURE: An enlarged SP:AP
      ratio (> or = 0.40) was used as the diagnostic criterion for endolymphatic
      hydrops. RESULTS: Overall, an enlarged SP:AP ratio was found in 75% of ears
      before treatment and 78% after treatment. The SP:AP ratio, when enlarged,
      remained enlarged in 91% of ears. A nonenlarged SP:AP ratio before treatment
      became enlarged after treatment in 41% of ears. In American Academy of
      Otolaryngology-Head and Neck Surgery stage 1 Meniere's disease (pure-tone
      threshold average < or = 25 dB), an enlarged SP:AP was found in 58% of ears
      before treatment and 79% after. Twenty-five (89%) of 28 patients followed for 2
      years were free of vestibular symptoms after treatment, and in 22 patients (79%),
      the SP:AP remained enlarged. The distribution of an enlarged SP:AP ratio was
      associated with the duration of disease (chi-square = 33.5552, p < 0.01).
      CONCLUSIONS: The development of endolymphatic hydrops, as indicated by an
      enlarged SP:AP, is part of the progression of Meniere's disease. The longer the
      duration of the disease, the more likely the SP:AP ratio will be enlarged. These
      findings indicate that endolymphatic hydrops as detected by ECoG was not reversed
      in this study by the treatments used. Despite the absence of definitive spells of
      vertigo in most patients, endolymphatic hydrops as evidenced by an enlarged SP:AP
      ratio persisted.

PMID- 9661759
TI  - Management of nonacoustic cranial nerve neuromata.
AB  - OBJECTIVE: This study aimed to review the authors' experience with diagnosis and
      management of nonacoustic neuroma of the cerebellopontine angle and skull base.
      In addition, management strategies for each type of tumor are suggested. STUDY
      DESIGN: A retrospective review of the charts of patients at the authors'
      institutions who underwent surgery for neuroma of the fifth through twelfth
      cranial nerves, between the years 1980-1996, was undertaken. Presenting symptoms,
      diagnostic techniques, and treatment are discussed for each type of lesion.
      PATIENTS: Four individuals with trigeminal neuroma, 1 individual with abducens
      neuroma, 40 individuals with facial neuroma, 3 individuals with glossopharyngeal
      neuroma, 21 individuals with vagal neuroma, 1 individual with accessory neuroma,
      and 4 individuals with hypoglossal neuroma participated. INTERVENTIONS: Surgical
      resection versus observation was examined. MAIN OUTCOME MEASURES: Freedom from
      recurrence or complication was measured. RESULTS: Surgical resection achieved in
      all patients, aside from the patient with abducens neuroma who is being observed,
      was measured. CONCLUSIONS: The preoperative diagnosis of nonacoustic lower
      cranial nerve neuroma is fairly common at the authors' institutions. Each type of
      neuroma requires its own tailored surgical approach once a decision has been made
      to resect the tumor.

PMID- 9661760
TI  - Preoperative identification of patients at risk of developing persistent
      dysequilibrium after acoustic neuroma removal.
AB  - OBJECTIVE: This study aimed to identify preoperative signs or symptoms that
      correlate with poor postoperative vestibular compensation after acoustic neuroma
      removal. STUDY DESIGN: The study design was a retrospective chart review.
      SETTING: The study was conducted at a tertiary care center. PATIENTS: A total of
      210 patients who had acoustic neuromas removed via the retrosigmoid approach from
      January 1, 1990, to July 1, 1995, participated. MAIN OUTCOME MEASURES: Persistent
      dysequilibrium for > 3 months after surgery was measured. RESULTS: Age (p =
      0.002), gender (p = 0.007), presence of preoperative dysequilibrium (p = 0.005),
      duration of preoperative dysequilibrium > 3.5 months (p = 0.003), and central
      findings on electronystagmography ( p < 0.001) were related to poor outcome.
      CONCLUSIONS: The authors found 31% of patients to have dysequilibrium lasting > 3
      months after surgical removal of an acoustic neuroma. Age > 55.5 years, female
      gender, constant preoperative dysequilibrium present for > 3.5 months, and
      central findings on electronystagmography were associated with a worse outcome.

PMID- 9661761
TI  - Otalgia. An isolated symptom of malignant infratemporal tumors.
AB  - OBJECTIVE: This study aimed to review a series of 18 patients with malignant
      infratemporal fossa tumors who presented with otalgia as the primary symptom.
      STUDY DESIGN: This was a retrospective case analysis. SETTING: All patients were
      evaluated and treated at a tertiary care academic medical institution. PATIENTS:
      Eighteen patients evaluated for otalgia in a normal-appearing ear, between July
      1988 and July 1996, who were found to have a malignant infratemporal fossa tumor
      participated. INTERVENTIONS: Diagnostic testing included radiographic evaluations
      and tissue sampling through fine-needle aspiration cytology. Treatment methods
      were histology dependent. MAIN OUTCOME MEASURES: The time between the onset of
      otalgia and the tumor diagnosis was recorded. Overall treatment outcomes were
      reviewed. RESULTS: The period between the onset of otalgia and tumor diagnosis
      ranged from 4-21 months with a mean of 7.5 months. Adenoid cystic carcinoma was
      the most commonly seen tumor in this series of patients. CONCLUSIONS: The
      infratemporal fossa is a relatively protected region that may be the site of
      malignant neoplasms causing the isolated symptom of otalgia.

PMID- 9661762
TI  - Cochlear neuromas.
AB  - OBJECTIVE: This study aimed to review the clinicoradiographic findings in 16
      patients with unilateral cochlear neuromas. STUDY DESIGN: The data included in
      this presentation were obtained from a retrospective case review. SETTING: The
      study was conducted at a tertiary care academic institution. PATIENTS: Patients
      of any age, gender, or race with a unilateral cochlear neuroma participated.
      INTERVENTIONS: Standard audiometric and radiographic assessment was performed.
      MAIN OUTCOME MEASURES: Progressive sensorineural hearing loss was measured.
      RESULTS: Sensorineural hearing loss is out of proportion to the size of the tumor
      (< 8 mm in all 16 patients). CONCLUSIONS: Gadolinium-enhanced magnetic resonance
      imaging in the axial and coronal planes can help identify cochlear neuromas in
      selected patients with unilateral sensorineural hearing loss.

PMID- 9661763
TI  - Advances in monitoring of seventh and eighth cranial nerve function during
      posterior fossa surgery.
AB  - OBJECTIVE: This study aimed to illustrate some recent advances in intraoperative
      monitoring of the seventh and eighth cranial nerves (i.e., direct recording of
      cochlear nerve action potentials [CNAPs] and facial nerve action potentials
      [FNAPs]). STUDY DESIGN: Reports of representative cases and average postoperative
      results obtained in subjects submitted to cerebellopontine angle surgical
      procedures are examined. Results obtained in patients with direct recording
      techniques are compared with those obtained with the classical monitoring
      techniques (auditory brain stem response [ABR], electrocochleography [ECoG],
      facial electromyography [EMG]). SETTING: The study was conducted at an Ear Nose
      and Throat Department, University of Verona, Verona, Italy. INTERVENTION:
      Intraoperative monitoring during cerebellopontine angle surgery was performed.
      RESULTS: Patients monitored with direct audiomonitoring techniques presented
      better postoperative auditory functions compared to patients monitored with ABR.
      The FNAP and EMG groups showed FN outcome that did not differ significantly.
      CONCLUSIONS: Intraoperative monitoring of cranial nerves furnishes a valid tool
      for identification of neural structures, prevention of damage, understanding of
      the pathophysiology of damage, and prediction of postoperative function. The
      fundamental prerequisite for obtaining optimal benefits from monitoring is the
      use of techniques of direct and continuous electrophysiologic recording with
      instantaneous feedback to the surgeon, such as CNAPs and FNAPs.

PMID- 9661764
TI  - A novel psychophysical illusion resulting from interaction between horizontal
      vestibular and vertical pursuit stimulation.
AB  - HYPOTHESIS: The hypothesis was tested that the perception of an object's motion
      is made in relation to an internal reference center (IRC), which is under the
      influence of vestibular receptors. Experiments were designed to evaluate whether
      induced vestibular self-motion will interact linearly with the perception of a
      visual target (VT). BACKGROUND: The major complaint of vestibular patients is
      vertigo, an illusion of motion. However, there is as yet no objective method to
      measure this illusion, which is produced by vestibular stimulation. METHODS: Six
      subjects were instructed to track a vertically moving VT while sinusoidally
      rotating (0.2 Hz) in the yaw plane at 14, 28, and 42 degrees/s. Eye movements
      were monitored by electro-oculographic electrodes. RESULTS: During visual
      vestibular interaction, all subjects perceived a VT moving obliquely while the
      eyes moved in the vertical plane. The subject then tilted the VT trajectory until
      vertical was perceived. At this time, the eye had an oblique vectorial
      trajectory. Interactive horizontal eye velocities, both vertical and horizontal
      components, were compared with those from rotation in the dark, showing a strong
      positive linear relationship (slope = 0.96, r = 0.84, n = 18). CONCLUSIONS:
      Results support the hypothesis of an egocentric sense of orientation whereby
      velocity of external objects is evaluated in relation to an IRC that is dependent
      on the status of the vestibular system. These methods may lead to new techniques
      for clinical evaluation of vestibular patients.

PMID- 9661766
TI  - Imaging case of the month: jugular diverticulum.

PMID- 9661765
TI  - Adaptive bone modeling in the middle ear is substance-P dependent.
AB  - HYPOTHESIS: Localized bone modeling in the middle ear is substance-P dependent.
      BACKGROUND: Processes of local bone modeling and remodeling in the middle and
      inner ear lead to destructive processes such as otosclerosis and chronic otitis
      media. The cellular events associated with these processes are known, but the
      mechanisms of the control and activation of the involved cells are not. The
      authors hypothesized that one of the control mechanisms of local bone modeling is
      related to the action of a neuropeptide, substance-P and that capsaicin, which
      depletes substance-P, would block modeling in the gerbil model of adaptive bone
      modeling. METHODS: One middle ear of each of 24 Mongolian gerbils was pressurized
      to 10 mmHg to induce adaptive bone modeling. Half of the animals were pretreated
      with capsaicin and half received vehicle alone. At the end of the 5-day
      experimental period, the bulla was studied histomorphometrically for osteoclastic
      and osteoblastic activity. RESULTS: Capsaicin pretreatment inhibited the percent
      of bone occupied by osteoclasts on the inner surface of the bulla and the rate of
      mineralization of bone on the outer surface of the bulla. CONCLUSIONS: It is
      likely that substance-P is a mediator of localized adaptive bone modeling in
      vivo. Processes of bone modeling and remodeling in the middle and inner ear may
      be under neural control.

PMID- 9661767
TI  - Routine preoperative imaging in chronic ear surgery.
AB  - OBJECTIVE: This article provides an overview of the practice and utility of
      preoperative radiologic studies in chronic otitis media (COM). DATA SOURCES: A
      literature search of English language clinical and basic science publications was
      performed. Major otolaryngology texts were reviewed. Special attention was given
      to the clinical experience and recommendations of experienced otologic surgeons
      and radiologists regarding the use of radiologic studies in COM. CONCLUSIONS:
      There is no single accepted standard for the use of preoperative imaging in
      uncomplicated COM. Imaging studies, especially computed tomography (CT), can
      provide information regarding the nature and extent of disease, which may not be
      apparent on the basis of clinical findings alone. This information may impact the
      patient's operative management, especially in complex or revision cases. Each
      clinician must assess the benefits derived from these studies in his or her own
      practice.

PMID- 9661768
TI  - [Substantiation of radiation quality coefficient dependence on LET in application
      to the assessment of early radiobiological effects].
AB  - Radiobiological studies targeted at determination of the coefficients of relative
      biological effectiveness (RBE) of various radiations in comparison with the
      standard X-ray radiation at 180-250 keV maximum were reviewed. Comparison of
      reactions of the body as a whole and its specific systems shortly after acute
      irradiation revealed the character of the relationship of RBE coefficients to
      LET. These data are essential for more careful estimation of radiation risk
      during space missions when, in parallel with chronic exposure to determinant
      sources, i.e. GCR and ERB, crew members may be also subjected to comparatively
      brief SCR attacks, particularly during solar proton events with high fluences.

PMID- 9661769
TI  - [Hematological investigations in conditions of long-term space flights].
AB  - In the nearly 15-month mission aboard MIR the cosmonaut-physician and members of
      three crews (MIR-15, -16, and -17) carried out a program of hematological
      investigations. Most of the changes related to the red blood system and included
      reduction in hemoglobin and hematocrit. Erythrocytes had decreased concentration
      and took on abnormal forms. There were also signs of altered metabolism of
      erythrocytes. Of interest are phase-by-phase variations in the levels of
      erythrocytes in the course of long-term stay in microgravity, and absence of a
      convincing correlation between hemoglobin, erythrocyte and hematocrit levels. But
      for lymphocytosis that returned to the norm already on the first day of recovery,
      no material changes occurred to the leukocyte profile. Investigations at the
      landing site displayed erythropenia, decreased reticulocytes and ensuing
      reticulocyte reaction, and gradual regain of the erythrocyte number that can be
      viewed as a normal physiological reaction of the blood system to the set of
      factors of spaceflight and early readaptation. Besides, the investigations showed
      a large individually of blood reactions to prolonged stay in space flight.

PMID- 9661770
TI  - [Role of age in +Gz and +Gx tolerance by female candidates to astronauts].
AB  - Analyzed was the role of age in the tolerance of +Gz (up to 5 units) and +Gx (up
      to 8 units) by female candidates to cosmonauts on the stage of initial centrifuge
      selection in the years of 1979 through to 1993. Selection was made of 26 healthy
      non-flying women aged 23 to 39 who were divided into 4 groups with 5-year
      intervals. Female tolerance of g-loads and shifts in a number of physiological
      parameters during centrifugation were discovered to be age-dependent. The poorest
      tolerance of +Gz and +Gx loads was typical of women below 25 years, the best, at
      the age of 31 to 40 years. It was stated that tolerance of these demanding g
      loads by women, especially below 30, was generally worse compared with men. There
      were also some distinctions in the cardiovascular response in women and men.
      These results point to the significance of centrifugation in selection female
      candidates to cosmonauts irrespective of their age.

PMID- 9661771
TI  - [Effect of 3-day immersion on calf blood flow during physical loading test].
AB  - The effect of simulated gravitational unloading (dry immersion) on blood flow in
      the calf during upright locomotion was studied. Six subjects performed graded
      exercise before and after 3-day immersion. Arterial inflow to the calf was
      evaluated during abrupt cessation of treadmill walking/running on the phase of
      changing the leg with the plethysmographic technique of determining the
      haemodynamic effect of muscle pump. Before immersion, testing increased the calf
      blood flow on transition from walking to running and stayed at plateau or
      decreased with further speed rise. After immersion, the calf blood flow tended to
      decrease during running. At maximal running speed and heart rate > 185 beats/min,
      calf blood flow was significantly lower post than prior to immersion. We believe
      that immersion enhances the competitive interaction of local operational
      mechanisms of hyperemia and central vasoconstrictive influences directed at
      maintaining "the circulatory homeostasis".

PMID- 9661772
TI  - [Effect of ephedrine and support loads on development of osteopenia and growth of
      shin bones in suspended rats].
AB  - Effects of graded support loads and stimulators of the central nervous system
      (ephedrine and strychnine) on growth of bones and the volume of spongy bone
      tissue in the proximal metaphyses of the shin bones were studied in the 14-day
      experiment with rats suspended by tail in the orthostatic position. It is
      indicated that the support loads in combination with ephedrine injection prevent
      the suspension-induced inhibition of bone growth and development of osteopenia of
      spongiosa of metaphyses. The preventive effect of support loads and ephedrine
      relates with their stimulating influence on the functional activity of the STH
      cells of adenohypophysis producing the growth hormone.

PMID- 9661773
TI  - [Effect of weightlessness on rats endocrine system development].
AB  - The histological structure of the brain and spinal cord, visual, olfactory,
      auditory and vestibular analysers, and endocrine organs (epiphysis, hypophysis,
      thyroid and parathyroid glands) were investigated in newborn rats delivered by
      females who had been exposed to weightlessness a half of the pregnancy period.
      Analysers of the flight animals did not have any marked deviations from the norm.
      Loci of neurone degeneration resembling porencephaly but less massive were
      revealed in various brain portions (cortex, hypocampus, metencephalon, spinal
      cord) of the infant rats developed in space flight. Endocrine studies showed
      accelerated differentiation of the thyroid cells secreting thyroid hormones, C
      cells, and parathyroid cells in most of the infant rats of the flight group. The
      test animals reduced the size of epiphysis and the number of pinealocytes.
      Adenohypophysis was found to be smaller with altered spatial distribution of the
      trabecular system. The changes look quite impressive but do not threaten
      viability of the animals.

PMID- 9661774
TI  - [Some peculiar features of liquid supply to the root medium of plants growing in
      microgravity].
AB  - Sixteen point probes monitored moisture level in the root medium of the wheat
      plants grown in greenhouse SVET on the MIR/NASA space science program. The
      article outlines types of water migration in the absence of gravity.
      Hydrophysical characteristics of perspective root media have been explored.
      Results of the water supply monitoring and control in the course of experiment
      are reported. The authors put forward porous root media to facilitate water
      migration and aeration.

PMID- 9661775
TI  - [Evaluation of super dwarf wheat growth and development in greenhouse "Svet"
      during cultivation in inhabited pressurized chamber].
AB  - Goals of the 3-month experiment GREENHOUSE using the equipment of greenhouse SVET
      (ECO-PSY-95) were to feature growth and development of wheat through the entire
      cycle of ontogeny under the maximally mimicked MIR environment, and to try out
      the procedures and timeline of space experiment GREENHOUSE-2 as a part of the
      fundamental biology investigations within the MIR/NASA space science program.
      Irradiation intensity (PAR) was 65 W/m2 and 38 W/m2 in the experiment and
      laboratory control, respectively. Values of other environmental parameters were
      MIR average (18-25 degrees C, relative air humidity in the interval between 40%
      and 75%, total gas pressure of about 660 to 860 mm Hg, partial oxygen pressure
      within the range from 140 to 200 mm Hg, partial carbon dioxide pressure up to 7
      mm Hg). Experimental results showed that wheat cultivation in inhabited chamber
      under a modified lighting unit providing greater irradiation of the crop area
      produced more plant mass although seed production dropped. Low grain content in
      ears could be the aftermath of the gaseous trace contaminants in the chamber
      atmosphere.

PMID- 9661776
TI  - [Lymphoid tissue of mice spleen in the delayed periods following a single gamma
      irradiation].
AB  - Morphofunctional state and recombination of cell composition of the spleen
      structural components were studied in mice Balb/c at delayed (post-irradiation
      days 21, 30, and 58) periods following a single gamma-irradiation by 6.9 Gy. At
      none of these time points did the lymphoid structural components of the spleen
      complete their morphological and cytological recovery. Morphological disturbances
      included poor development of germinative centers and marginal zones in lymphadens
      and periarterial lymphoid heads (PALH). Recovery of lymphoid cell population did
      not go on same pattern. Thus, by day 58 of recovery, in PALH small lymphocytes
      regained basal level but rose concentration to 79% in the lymphadens without
      germinative centers and to 60% in the lymphoden mantle and red pulp. Elevation of
      mitotic and cell differentiation activities was not equal. Destructive processes
      approached normal values in PALH and red pulp and remained by 85% beyond basal
      values in lymphodens. Mature/immature plasmatic cells ratio was modified.
      Moreover, plasmocytes (mature cells) that are responsible for humoral immunity,
      localized in unordinary sites, i.e. in PALH and lymphodens without germinative
      centers. Adaptive changes observed in the red pulp at delayed time-points after
      irradiation were manifested by development of myelopoiesis focuses with high
      concentrations of young forms of neutrophils and megakaryocytes.

PMID- 9661777
TI  - [Effect of mild-frequency ultraviolet radiation on mice splenic lymphocytes].
AB  - Investigation of the action of mid-frequency ultraviolet radiation (302 nm) on
      isolated lymphocytes of mice spleen pointed out that intracellular pH of
      lymphocytes starts decreasing from 0.3 J/cm2. Dose rise above 2.5 J/cm2 increases
      the number of cells with damaged plasmatic membrane within the lymphocyte
      population and aggravates the ability of cells to accumulate fluorescein
      fluorochrome as a product of intracellular fluorescein diacetate hydrolysis.

PMID- 9661778
TI  - [Reaction of different cell populations in mouse thymus to a single gamma
      irradiation].
AB  - Cytoarchitectonics of the functional zones of thymus was studied with the
      morphometric technique. Reactions of different cell populations to a single gamma
      irradiation at a dose of 6.9 Gy were demonstrated. Acute reaction in thymus
      showed up already on the first day following exposure. Reparation began three
      days later and proceeded in two stages one of which (day 7) was accomplished by
      survived cells and the other (day 21), owing to the influx of precursors from
      recovered bone marrow. It was found that thymic substantia medullaris was less
      compromised by radiation as compared with cortex. This was due to the presence of
      more resistant lymphoid cells and activation of lymphocytopoiesis proper. It was
      also established that in the post-irradiation period (days 1 through to 58)
      cytoarchitectonics of the thymic functional zones has failed to complete
      recovery. Moreover, a second thymus depletion was observed on day 58.

PMID- 9661779
TI  - [Comparative evaluation of microorganisms biological characteristics isolated in
      the orbital complex "Mir" on different phases of its operation].
AB  - Colonizing and bio-destructive activities and pathogenetic potential of
      microorganisms isolated from the MIR environment at different phases of its
      operations were tested and evaluated in comparison with standard "museum"
      cultures of analogous species. Comparison of bacterial and fungal species
      revealed certain cultural, biochemical, and morphological distinctions of the
      "flight" strains. However, to assess the character and the risk associated with
      peculiar evolution of microflora in long-term space missions, more careful
      investigations should be followed with the use of the strain genetic labeling and
      other modern techniques.

PMID- 9661780
TI  - [Model study of ozone microbial decontamination effectiveness of space station
      environment].
AB  - Modeling experiments were performed to evaluate bactericide and fungicide effects
      of small ozone concentrations (0.3 mg/l of water and 47 mg/m3 of air) that can be
      generated onboard spacecraft following one hour after treatment. Over the period
      of treatment, reduction in aquatic microorganisms made up, depending on biotest
      in use, hundred and more times; concentration of atmospheric microorganisms
      showed a 5- to 10-fold reduction. The demonstrated effectiveness of ozone shows
      that it may advantage sterilization and cleaning from microorganisms a number of
      life support systems aboard manned space vehicles and stations.

PMID- 9661781
TI  - [Clinical-physiological aspects of normobaric hypoxic training effects on
      functional status of patients with neurocirculatory dystonia].
AB  - Profiles of external respiration and circulation, self-assessment of health,
      mental performance, sensory functions, and peripheral blood were studied in
      patients with neurocirculatory dystonia in the course of normobaric hypoxic
      training. The hypoxic training proved to successfully normalize arterial
      pressure, eliminate cardiac arrhythmias, and benefit general condition.
      Substantial strengthening of hypoxic resistance was stated along with an oxygen
      debt reduction during hypoxia, improvement of sensory coordination and mental
      performance, and activation of erythropoiesis.

PMID- 9661782
TI  - [Role of ultrasonic investigations in diagnosis of pancreatic diffuse pathology
      in flying personnel].
AB  - The article presents data of a complex clinical/radiation examination of flying
      personnel with diagnosed diffuse pathologies of pancreas. Consistent patterns of
      the fibrotic process in pancreatic parenchyma were related to professional
      specifics. Preponderance of ultrasonic investigations, mathematical analyses, and
      X-ray computer tomography for the enhanced diagnostic algorithm for the medical
      certification of flying personnel were demonstrated.

PMID- 9661783
TI  - [Effect of hypokinesia of various duration on acid-alkaline balance in rat's
      blood].

PMID- 9661784
TI  - [Delayed technique of glucose quantification in biological objects].

PMID- 9661785
TI  - [Plasma membrane proteinases from lymphoid cells and their biological functions].
AB  - The properties, distribution, and biological functions of several proteases from
      the plasma membrane of lymphoid cells are reviewed: dipeptidyl peptidase IV,
      neutral endopeptidase, aminopeptidases A and N, and a new protease of the family
      of adamalysins. these enzymes (designated as ectopeptidases) are integral
      membrane proteins whose molecules are mainly located extracellularly. Their
      functions involve proteolysis on the cell surface: the formation and inactivation
      of regulatory peptides and growth factors, as well as modification of cell
      surface proteins. The biological significance of a partial proteolysis of the
      plasma membrane proteins and the resulting soluble isoforms are discussed. An
      analysis of the data suggests that ectopeptidases from lymphoid cells are
      elements of the sensory system of the cell and are involved in the regulation of
      its physiological response to external factors and in the coordination of cell
      cell interactions.

PMID- 9661786
TI  - [New studies on natural inhibitors of proteolytic enzymes].
AB  - New data on proteolytic enzyme inhibitors and mechanisms of their interaction
      with the enzymes are reviewed. In recent years, a number of new inhibitors
      comprising families earlier unknown have been described such as proteins from the
      parasitic nematode Ascaris lumbricoides, ecotin from the periplasm of Escherichia
      coli, proteins PMP-C and PMP-D from locust Locusta migratoria, and hirustasin
      from the medicinal leech Hirudo medicinalis. At the same time, some proteins that
      may be assigned to inhibitors on the basis of their structures were found to
      perform other (not inhibitory) functions. Thus, the family of the Kunitz soybean
      trypsin inhibitor includes plant storage proteins and proteins whose synthesis is
      induced by stress factors. Numerous inhibitors interacting with the enzymes by
      mechanisms other than the substrate-like ones were identified, such as
      ornithodorin and anticoagulant peptide from tick Ornithodoros moubata (inhibitors
      of the blood clotting system proteases), an inhibitor from snake (Bothrops
      jararaca) venom, and ecotin, an inhibitor of serine proteases with an unusually
      broad specificity range. Special emphasis is placed on enzyme inhibition with
      propeptides and the mechanism of this process.

PMID- 9661787
TI  - [Modification of basic pancreatic trypsin inhibitor by fatty acid derivatives].
AB  - A procedure was developed for the modification of basic pancreatic trypsin
      inhibitor (BPTI) by N-hydroxysuccinimide esters of oleic and stearic acids in a
      DMSO-DMF-dioxane-pyridine mixture with a temporary citraconyl protection of the
      amino group belonging to its active site. The BPTI derivatives containing from
      one to three acylated amino groups were obtained. It was shown that the
      hydrophobized BPTI with one amino group modified retained practically the full
      activity of the native inhibitor. An increase up to three acylated groups
      resulted in a decrease in the specific activity of the inhibitor to 28% of the
      initial activity. An increase in hydrophobicity of the modified inhibitors was
      demonstrated by the spectral method and by the distribution in a water-triton X
      114 system.

PMID- 9661789
TI  - [Phase transition in the matrix as a regulator of enzymatic activity of
      proteinases].
AB  - The kinetic behavior of proteolytic enzymes immobilized in thermosensitive
      hydrogels was studied at the phase transition (collapse) of the carriers. The
      dependence of the activity of immobilized enzymes on the state of the matrix
      allows the use of the hydrogel phase transition to regulate the activity of
      immobilized enzymes. Several cases of such regulation were demonstrated.

PMID- 9661788
TI  - [Inhibition of formation of complement C5-convertase].
AB  - Control of the formation of complement C5-convertase is an important factor in
      maintaining human homeostasis. Some physiologically active endogenous and
      exogenous substances were shown to be capable of exerting such control. A method
      was developed for studying the influence of the effectors on the formation of
      classical-complement-pathway C5-convertase from C3-convertase stabilized by
      nickel ions. Immunoglobulins G and M, recombinant alpha and gamma interferons,
      serotonin, epinephrine, histamine, and ethanol were studied as effectors. The
      binding constants of the effectors with C3b, the active C3 component, and the
      values of the maximal effect were determined to evaluate the physiological
      importance of the effectors. The inhibition of C5-convertase generation was
      observed in all cases except for IgG and IgM (rheumatoid factor), which showed no
      effect and activating effect, respectively.

PMID- 9661790
TI  - [Threshold mechanism of the control of cascade proteolysis].
AB  - The immune lysis rate of erythrocytes vs. the concentration of particular
      complement components was studied. It was found that in the presence of component
      C1 (but not C3) and factors B and D, the cells undergo lysis after the
      concentration of these compounds exceeds a "threshold" value. The threshold molar
      concentrations of factors D and B exceeded 5- and 20-fold, respectively, that of
      component C1. The multiplicity and different capacities of the thresholds allow
      the fragmentary activation of cascade proteolysis at stretches between
      neighboring thresholds without the total realization of the final effect of the
      system (cell lysis, clot formation, etc.). The resulting peptideby-products
      (bypass peptides) may possess their own biological activity. It is the generation
      of various bioregulators that appears to be the main function of the cascade
      proteolytic systems functioning in the subthreshold regime.

PMID- 9661791
TI  - [Synthesis and characterisation of ATP-dependent forms of Lon-proteinase with
      modified N-terminal domain from Escherichia coli].
AB  - The functional domain boundaries of the ATP-dependent Lon proteases were
      identified by comparative analysis of the amino acid sequences of the enzymes
      from evolutionarily distant organisms. Modified forms of the Escherichia coli Lon
      protease with the elongated or substituted N-terminal domain and a truncated
      enzyme lacking the N-terminal domain were obtained through genetic engineering
      methods. Analysis of the enzymatic properties of the resulting modified forms of
      Lon protease revealed the importance of the N-terminal domain in its function.

PMID- 9661792
TI  - [Combined thrombolysis by pharmacokinetically different plasminogen activators].
AB  - Prospects for the search for thrombolytic compositions on the basis of short-term
      and long-term acting plasminogen activators were shown. These will be useful as
      potential ambulance remedies for effective prehospital treatment. Combined
      proteolysis by plasminogen activators with complementary action mechanisms and
      significantly different pharmacokinetic behavior was suggested for this purpose.

PMID- 9661793
TI  - [Protein engineering of uridine phosphorylase from Escherichia coli K-12. I.
      Cloning and expression of uridine phosphorylase genes from Klebsiella aerogenes
      and Salmonella typhimurium in E. coli].
AB  - Genes of uridine phosphorylases (udp) from Klebsiella aerogenes and Salmonella
      typhimurium were cloned and expressed. Highly effective producer strains of the
      corresponding proteins were constructed. Enzymic properties of the UPases
      obtained were studied and compared with those from the Escherichia coli enzyme.
      Mutant forms of UPase from E. coli (D5E, D5N, D5A) were prepared by site-directed
      mutagenesis techniques. It was shown that the Asp5 residue plays an insignificant
      role in the formation of the active form of the protein.

PMID- 9661794
TI  - [Factual databases in bioorganic chemistry. Analytical review].
AB  - The main scientific sequence databases of interest for researchers working in the
      field of bioorganic chemistry are reviewed. Information is given concerning
      possibilities for rapid access and efficient search for needed information,
      postal and e-mail addresses, and literature sources in which these databases are
      comprehensively described.

PMID- 9661795
TI  - The myelodysplastic syndromes: towards a functional classification.
AB  - The French-American-British classification of myelodysplastic syndromes (MDS) has
      contributed greatly to better communication and conduct of clinical trials.
      However, the advent of novel cytogenetic, immunological and molecular techniques
      in recent years warrant some alterations to this purely morphological
      classification. This review aims at highlighting the advances which reflect more
      closely the unique biological and clinical features of various subtypes of MDS.
      We propose a comprehensive classification of MDS, to include the newly defined
      categories, as well as those not included in previous classifications, such as
      the therapy-induced and hereditary MDS. We hope that this classification will
      help in focusing attention on the biological features of MDS, the understanding
      of which will be crucial to combat this disease.

PMID- 9661796
TI  - New approaches to the delivery of anticoagulant services.
AB  - Anticoagulant services are changing in response to the increasing demands on the
      service. New approaches to the delivery of the service are evolving with more
      local delivery of services and a shift in the service from secondary to primary
      care. This change has been assisted by the development of near patient testing
      devices and the use of computerized anticoagulant decision support systems that
      are increasingly used in both secondary and primary care. The evolving role of
      the clinical nurse/pharmacist in the provision of this service is an important
      development enabling more rapid discharge of patients and the provision of local
      delivery of service.

PMID- 9661797
TI  - Management of warfarin (coumarin) overdose.
AB  - Treatment with coumarin oral anticoagulants, such as warfarin, is effective
      antithrombotic therapy, but patients treated with these drugs are at significant
      risk of bleeding. The risk of haemorrhage increases with increasing intensity of
      anticoagulation and overanticoagulation is common. Reversal can be achieved by
      stopping the coumarin drug or administration of vitamin K, fresh frozen plasma or
      coagulation factor concentrates. However, there are surprisingly few studies
      defining the optimum dose of these products and there are no randomized studies
      comparing the relative benefit and risk of coagulation factor concentrates versus
      fresh frozen plasma. Guidelines for the management of overdose are based on level
      III and IV evidence and are, therefore, only grade B recommendations at best.
      Further studies are required to determine the most effective use of products and
      the dose required for safe reversal of overanticoagulation.

PMID- 9661798
TI  - Neoantigens and antibodies to factor VIII.
AB  - It is well known that 10-20% of severe haemophiliacs are likely to develop
      inhibitors to factor VIII, usually soon after the commencement of therapy. Two
      recent inhibitor outbreaks have occurred in patients treated for a number of
      years on switching to a product subjected to additional virus inactivation. Hence
      the incidence of inhibitor formation may be affected by the type of product used
      for treatment and the potential for processing to result in 'neoantigens'.
      Examination of the parts of factor VIII interacting with inhibiting antibodies,
      and the effect of various therapies on these, can teach us something about the
      mechanisms involved in antibody formation. However, the development of pre
      clinical assays to assess products and processes for neoantigen formation should
      allow the prevention of inhibitor outbreaks. This review summarizes current in
      vitro and in vivo approaches to this problem, concluding that most available
      assays are inadequate for this purpose, with competitive immunoassay and
      phospholipid binding providing the most hopeful route forward.

PMID- 9661799
TI  - Developmental biology of erythropoiesis.
AB  - A newborn infant represents the culmination of developmental events from
      conception through organogenesis. Red cells are critically important for survival
      and growth of the embryo. During development, erythropoiesis occurs in two
      distinct forms. The first 'primitive' form consists of nucleated erythroblasts
      that differentiate within the blood vessels of the extraembryonic yolk sac. The
      second 'definitive' form consists of anucleate erythrocytes that differentiate
      within the liver and third trimester bone marrow of the fetus. While adult bone
      marrow and cord blood now serve as sources of stem cells for the treatment by
      transplantation of genetic and malignant diseases, the developmental origin of
      hematopoietic stem cells has not been determined. During the third trimester the
      fetus grows rapidly and the production of red cells is approximately 3-5 times
      that of adult steady state levels. Birth brings dramatic changes in oxygenation
      and erythropoietin production that result in a tenfold drop in red cell
      production and in a transient 'physiologic' anemia. Other causes of fetal and
      infant anemias have their origins in development processes. These include globin
      gene switching in alpha and beta thalassemia, the expression of red cell antigens
      in alloimmune hemolytic disease, and the poorly understood defects in the
      regulation of erythropoiesis in Diamond Blackfan anemia. Even in the adult,
      vestiges of fetal erythropoiesis are evident during transient states of
      accelerated erythroid expansion. A better understanding of the development of
      erythropoiesis will bring improvements in the treatment of anemia, not only in
      the newborn, but also in the fetus and the adult.

PMID- 9661800
TI  - Enzyme therapy for Gaucher disease: the first 5 years.
AB  - Gaucher disease was first described by Philippe Gaucher in his 1882 medical
      thesis. Gaucher's original concept was of an unusual epithelioma of the spleen.
      By the early 1900s, Mandelbaum recognized the systemic nature of the disease.
      Several children with Gaucher disease were described at the turn of the century,
      but Rusca described a rapidly progressive fatal neurodegenerative type of
      disease, i.e. type 2, in the 1920s. The 'juvenile' form (type 3) of the disease
      was described in Sweden in the 1950s. In 1965, the deficient enzyme, acid beta
      glucosidase, was discovered and the lysosomal nature of the disease was
      elucidated. Currently, three variants of Gaucher disease have been defined
      clinically and are distinguished by the presence and severity of neuronopathic
      involvement (Table 1). Each of these clinical types has substantial phenotypic
      variation, but types 1 and 3 have significantly heterogeneous rates of disease
      progression and degrees of visceral organs involvement. The neuronopathic
      involvement in type 3 also has substantial variation in the age of onset and
      disease progression even within relatively isolated communities. An extensive
      review of the clinical and pathologic involvement by Gaucher disease is
      available.

PMID- 9661801
TI  - Genetic and non-genetic basis of essential hypertension: maladaptation of human
      civilization to high salt intake.
AB  - The relation between salt intake and hypertension has long been controversial.
      Available evidence provides conflicting results. However, biological and
      evolutionary insights into the structure and principle function of the kidney and
      the blood pressure sustaining machinery, with the extracellular fluid volume and
      the renin-angiotensin system acting as a central player, clearly indicate that
      salt has been a precious commodity in the terrestrial animal kingdom and that
      essential hypertension may be a consequence of the kidney's maladaptation to
      excess salt intake, which is specific to recent human civilization. This review
      provides a hypothesis to explain how and why hypertension develops and attempts
      to define the roles of genetic, non-genetic, and environmental factors in its
      pathogenesis.

PMID- 9661802
TI  - Increased functional Na(+)-K+ pump activity in the vasculature of fructose-fed
      hyperinsulinemic and hypertensive rats.
AB  - We hypothesized that hyperinsulinemia may alter insulin's ability to stimulate
      vascular Na+/K(+)-ATPase pump activity and modulate changes in vascular
      responsiveness associated with hypertension. We measured potassium-induced
      relaxation as an indicator of Na+/K(+)-ATPase pump activity in isolated femoral
      arteries from fructose-fed (FF) hyperinsulinemic, Sprague-Dawley rats. FF rats
      had higher mean arterial blood pressures than did normal diet-fed (NF) rats (FF,
      125 +/- 2.2, n = 20, vs. NF, 113.5 +/- 2.5 mmHg, n = 20, p < 0.05) and were
      hyperinsulinemic (FF, 64 +/- 4 vs. NF, 37 +/- 2, microU/ml insulin, p < 0.01). FF
      rats were more sensitive to KCl in the Na+/K+ pump bioassay (FF, 0.86 +/- 0.07, n
      = 21 vs. NF, 1.18 +/- 0.08, n = 17, p < 0.05, expressed as ED50 in mmol/l KCl).
      Exogenous insulin (100 mU/ml) increased Na+/K+ pump sensitivity in FF rats as
      compared with a boiled insulin control (insulin 45 +/- 6%, n = 11, vs. control,
      11 +/- 7%, n = 13, p < 0.01, expressed as percent increase in sensitivity, i.e.,
      ED50). There were no significant differences in Na+/K+ pump sensitivity between
      insulin and control responses in the NF animals (insulin 29 +/- 6%, n = 11, vs.
      control 46 +/- 5%, n = 10, NS). Dose-response curves were obtained in tail and
      femoral arteries from the same animals to norepinephrine and acetylcholine,
      basally and after exogenous insulin. FF vessels had reduced sensitivity to
      norepinephrine as compared with the NF group. Insulin increased sensitivity to
      acetylcholine-induced relaxations and increased AII-induced contractions in FF
      rat vessels. These data suggest that in the FF rat insulin's influence on the
      vascular Na+/K+ pump is enhanced and may modulate the changes in vascular
      responsiveness seen in this model.

PMID- 9661803
TI  - Long-term therapy with an ACE inhibitor, temocapril, reduces microalbuminuria in
      essential hypertension.
AB  - The present study was conducted to prospectively evaluate whether a new ACE
      inhibitor, temocapril, could modify urinary microalbumin excretion rate (UAE) in
      a group of hypertensive outpatients who had no evidence of renal impairment.
      Sixty-three outpatients (32 men and 31 women; mean age, 59.9 +/- 1.5 yr) with
      essential hypertension entered the study, all having been treated for at least 6
      mo with dihydropyridine calcium-channel blockers (CCBs: nitrendipine,
      nisoldipine, or amlodipine). Their blood pressures (BPs) had been controlled to
      adequate levels with the CCBs. None had overt proteinuria (determined by
      Albustix) or abnormal serum creatinine levels. After 3 mo of baseline observation
      under the previous treatment, the subjects were randomly divided into two groups.
      In group A (n = 31), the previously used CCBs were switched to temocapril, 2 to 4
      mg once daily for 12 mo, and BP was controlled at a level equivalent to that
      during CCB treatment. In group B (n = 32), the subjects were maintained on their
      previous treatment for a further 12 mo. The effect of temocapril on BP appeared
      to be clinically similar to that of the previously used CCBs, but it
      significantly decreased UAE as compared with the previous therapy. In group A,
      UAE decreased significantly (p < 0.01) from the baseline value of 38.9 +/- 5.1
      mg/g creatinine (Cr) to 22.2 +/- 4.2 and 25.3 +/- 5.6 mg/g Cr at the 6th and 12th
      months of temocapril therapy, respectively. In contrast, in group B UAE was
      unchanged (baseline 39.8 +/- 6.6 mg/g Cr; 6 mo, 44.6 +/- 6.8; 12 mo, 45.9 +/-
      7.7). In group A, 17 of 31 patients (54.8%) had abnormal UAE levels (> or = 29.5
      mg/g Cr) during previous therapy with CCBs, but 6 mo after switching to
      temocapril 25 of these patients (80.6%) had normal UAE (< 29.5 mg/g Cr). In group
      B, 15 of 32 patients (46.9%) had abnormal UAE levels during the observation
      period, and these abnormal UAE levels remained unchanged; 17 of the 32 patients
      (53.1%) had abnormal UAE levels after a further 6 mo of continued CCBs therapy.
      We conclude that long-term therapy with temocapril may provide renal protection
      by reducing UAE even in hypertensive patients with no evidence of renal
      impairment.

PMID- 9661804
TI  - Interaction of opioids and vasopressin in central action of angiotensin II in
      conscious rabbits.
AB  - It has been demonstrated that opioids modulate the renin-angiotensin and
      sympathetic nervous system. To clarify the interaction of central angiotensin II
      (Ang II) and endogenous opioids, we studied the effects of naloxone, an opioid
      antagonist, on cardiovascular and sympathetic responses to
      intracerebroventricular (i.c.v.) Ang II in conscious rabbits. I.c.v. Ang II (20
      ng/min) significantly increased mean arterial pressure (MAP), plasma epinephrine,
      and arginine vasopressin (AVP) levels, with no significant change in renal
      sympathetic nerve activity (RSNA) or heart rate. Pretreatment with intravenous
      naloxone (0.1 mg/kg) failed to alter the cardiovascular and neurohormonal
      responses to i.c.v. Ang II. To eliminate the effect of AVP on cardiovascular and
      sympathetic responses, [d(CH2)5Thy(Me)]AVP, a vasopressin V1-receptor antagonist,
      was given intravenously. Pretreatment with intravenous injection of the V1
      receptor antagonist (30 micrograms/kg) augmented the maximum increase in RSNA
      caused by i.c.v. Ang II (8.9 +/- 2.2 vs. 16.2 +/- 0.7%, p < 0.05). Combined
      pretreatment with naloxone and V1-receptor antagonist further increased MAP and
      RSNA in response to ICV Ang II (20 +/- 1 vs. 16 +/- 2 mmHg, p < 0.05, and 30.9 +/
      3.7 vs. 16.2 +/- 0.7%, p < 0.01, respectively). These results suggest that
      opioids and AVP synergistically modulate sympathetic outflow so as to suppress
      the central pressor action of Ang II in conscious rabbits.

PMID- 9661805
TI  - Chronic inhibition of nitric oxide in central nervous system does not cause
      hypertension.
AB  - Acute inhibition of nitric oxide (NO) synthase in the brain causes elevation of
      blood pressure and sympathetic excitation under anesthetized conditions. To
      investigate chronic effects of NO synthase inhibition in the central nervous
      system on blood pressure regulation in conscious unrestrained animals, we
      administered NG-monomethyl-L-arginine (L-NMMA), a potent NO synthase inhibitor,
      at low (22.5 mumol/kg) and high (67.5 mumol/kg) doses for 1 wk into the cisterna
      magna with an osmotic pump and measured mean arterial pressure (MAP) and heart
      rate (HR) by a telemetry method. The same dose of NG-monomethyl-D-arginine (D
      NMMA), an inactive isomer of L-NMMA, was administered to control rats. Chronic
      intracisternal administration of low-dose L-NMMA significantly decreased the
      brain nitrite/nitrate and NO metabolite contents as compared with D-NMMA (p <
      0.05). However, MAP and its variability, HR and its variability, and plasma
      norepinephrine levels did not differ between the two groups of rats at either low
      or high-dose treatment. Thus, chronic NO synthase inhibition in the central
      nervous system did not affect systemic hemodynamics or plasma norepinephrine
      concentrations despite the inhibition of brain NO. Our results suggest that
      endogenous NO in the central nervous system, at least as a whole, may not affect
      the systemic hemodynamics of chronic unanesthetized rats.

PMID- 9661806
TI  - Remission of hypertension: retrospective observations over a period of 20 years.
AB  - To clarify the background and outcome of hypertensive patients who have remission
      of their elevated blood pressure (BP) after a course of antihypertensive drug
      therapy, we designed a retrospective observational study. The clinical records of
      106 hypertensive men and women (BP, 164.3/104.4 mmHg) given antihypertensive drug
      treatment and subsequently examined every 1 to 3 mo for more than 20 yr were
      reviewed. The patients were divided into two groups: those who had remission (R
      group) and those who did not have remission (N-group). Patients were considered
      in remission if no significant elevation in BP was observed for more than 1 yr
      after withdrawing their medication. Remissions ranging in duration from 1.6 to
      21.7 yr (average duration, 6.3 yr) occurred in 19 of 106 patients (17.9%).
      However, anti-hypertensive drug treatment was eventually restarted in 17 of the
      19 patients. Before treatment, comparison of the R-group and N-group revealed no
      differences with respect to age, body weight, BP, or serum creatinine. In
      contrast, the proportion of patients who lacked high-voltage deflections in their
      electrocardiograms (ECG) as well as that of patients whose BP was well-controlled
      by a single medication was significantly greater in the R-group than in the N
      group (12/19 vs. 22/87, p < 0.05 and 10/19 vs. 13/87, p < 0.001, respectively).
      In addition, body weight in the R-group decreased significantly by the time drug
      therapy was withdrawn (p < 0.01). Finally, significantly more patients (14 of 19
      patients) entered remission in the spring and summer (p < 0.05) than at other
      times of the year. We conclude that remission occurs in a subset of well
      controlled hypertensive patients and may persist for several years or more.
      However, in the majority of patients, antihypertensive drug treatment will
      usually need to be restarted at some point. Patients who lack ECG high-voltage
      deflections and who are successfully treated with a single therapeutic agent are
      most likely to experience remission. Moreover, it appears that withdrawing
      patients from drug therapy in the spring or summer is more likely to yield a
      favorable outcome than at other times of the year.

PMID- 9661807
TI  - Mechanical stretch activates a pathway linked to mevalonate metabolism in
      cultured neonatal rat heart cells.
AB  - It is not certain whether activation of the Ras/mitogen-activated protein (MAP)
      kinase pathway is involved in cardiac hypertrophy. 3-Hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase inhibitors, such as lovastatin, prevent
      farnesylation of the Ras protein, which is critical for Ras's membrane
      localization and function. Therefore, the present study was undertaken to
      investigate the role of the Ras pathway, which is linked to mevalonate
      metabolism, in the mechanism of stretch-induced myocyte hypertrophy. Myocytes
      isolated from 1- to 2-day-old rats were cultured at 4.1 x 10(6) cells per well in
      a deformable silicon dish and incubated with serum-free medium for 7 days. The
      cultures were stretched by 15% on culture day 4. Stretch increased the RNA/DNA
      ratio by 20% to 26% on culture days 5 and 6 and the protein/DNA ratio by 18% to
      20% on culture days 6 and 7. Stretch accelerated rates of protein synthesis by
      24% on culture day 6. Stretch increased protein kinase C (PKC) activity, MAP
      kinase activity, and c-fos mRNA expression. A selective PKC inhibitor, calphostin
      C (1 x 10(-6) M), prevented the stretch-induced increase in PKC activity, but
      lovastatin (7.5 x 10(-6) M) did not. Lovastatin as well as calphostin C partially
      but significantly inhibited the stretch-induced increases in MAP kinase activity,
      c-fos mRNA expression, and protein synthesis. Pretreatment with both lovastatin
      and calphostin C completely inhibited the increases in these variables caused by
      stretch. Lovastatin as well as calphostin C prevents stretch-induced cardiac
      hypertrophy. These results suggest that mechanical stretch may activate the Ras
      pathway, which is linked to mevalonate metabolism, in cultured neonatal rat heart
      cells.

PMID- 9661808
TI  - Effects of lemildipine, a new calcium channel blocker, on renal microcirculation
      in SHR.
AB  - The effects of lemildipine, a new dihydropyridine calcium channel blocker, on
      renal hemodynamics and the tubuloglomerular feedback (TGF) mechanism were
      examined in anesthetized 9- to 10-wk-old spontaneously hypertensive rats (SHR).
      Lemildipine, 3 micrograms.kg-1 i.v., did not reduce mean blood pressure (MBP) but
      tended to increase GFR and increased urinary excretion of sodium (UNaV).
      Filtration fraction (FF) and fractional excretion of sodium (FENa) remained
      unaltered. An additional dose of lemildipine, 9 micrograms.kg-1 i.v., reduced MBP
      and renal vascular resistance. Renal plasma flow tended to increase, and GFR was
      unchanged. FF significantly fell. UNaV and FENa remained at the control level.
      Micropuncture experiments revealed that the maximal reduction in proximal stop
      flow pressure (SFP), an index of glomerular capillary hydrostatic pressure (Pgc),
      induced by perfusion of the loop of Henle was significantly reduced by high-dose
      treatment (8.8 +/- 1.3 vs. 13.7 +/- 1.9 mmHg in control). A high dose of
      lemildipine induced a rightward and slightly upward shift of the TGF curve; the
      steady-state tubular flow rate (V1/2) was increased, the maximal slope of the
      curve decreased, and SFP at V1/2 unaltered. A low dose of lemildipine did not
      affect TGF response. These results indicate that lemildipine attenuates the TGF
      response in SHR by dilating afferent arterioles and thereby corrects the left and
      downward shift of the TGF curve in SHR. In addition, the fall in FF indicates
      lemildipine-induced efferent arteriolar vasodilatation. Through balanced systemic
      and glomerular vasodilatation, lemildipine maintains the levels of Pgc and GFR in
      the face of reduced renal perfusion pressure.

PMID- 9661809
TI  - Discrepancy between screening blood pressure and ambulatory blood pressure: a
      community-based study in Ohasama.
AB  - We investigated factors underlying discrepancy between screening blood pressure
      and daytime ambulatory blood pressure (the difference) in a community-based
      population in northeastern Japan. Screening and ambulatory pressures were
      measured in 706 untreated subjects aged 20 yr or older. We analyzed the effects
      of age and blood pressure on the difference and then performed multivariate
      stepwise linear regression analysis using the difference as the dependent
      variable. The systolic difference positively correlated with age in men. Women in
      their 40s exhibited a large difference, disturbing the linear relationship
      between the difference and age. The difference positively correlated with the
      screening pressure in men and women. A positive difference (screening pressure >
      ambulatory pressure) was observed at screening pressures above 130/75 mmHg. The
      difference inversely correlated with the ambulatory pressure. Multivariate
      analysis demonstrated that body mass index and male sex were positively
      associated with the systolic and diastolic blood pressure differences. The
      daytime pulse rate was negatively associated with the systolic difference, and
      the standard deviation of daytime diastolic ambulatory blood pressure was
      positively associated with the diastolic difference. The diastolic difference in
      subjects with isolated systolic hypertension based on the screening pressure was
      significantly smaller than that in subjects with systolic/diastolic hypertension.
      The difference in subjects with isolated systolic hypertension based on
      ambulatory pressure was significantly higher than that in systolic/diastolic
      hypertension. When white-coal (isolated screening) hypertension was defined as a
      screening systolic pressure > or = 140 mmHg, a diastolic pressure > or = 90 mmHg,
      or both, and a 24-h ambulatory pressure < 136/87 mmHg in men and < 131/86 mmHg in
      women, white-coat (isolated screening) hypertension was present in 79 (56.8%) of
      139 subjects with screening hypertension. The results confirm that the
      discrepancy between screening and ambulatory blood pressure is due to a variety
      of factors, including age, sex, blood pressure levels, and baroreflex function.
      Our results indicate that screening blood pressure in elderly hypertensive
      patients should be evaluated carefully.

PMID- 9661810
TI  - Antibody phage display technology and its applications.
AB  - In recent years, the use of display vectors and in vitro selection technologies
      has transformed the way in which we generate ligands, such as antibodies and
      peptides, for a given target. Using this technology, we are now able to design
      repertoires of ligands from scratch and use the power of phage selection to
      select those ligands having the desired (biological) properties. With phage
      display, tailor-made antibodies may be synthesized and selected to acquire the
      desired affinity of binding and specificity for in vitro and in vivo diagnosis,
      or for immunotherapy of human disease. This review addresses recent progress in
      the construction of, and selection from phage antibody libraries, together with
      novel approaches for screening phage antibodies. As the quality of large naive
      and synthetic antibody repertoires improves and libraries becomes more generally
      available, new and exciting applications are pioneered such as the identification
      of novel antigens using differential selection and the generation of receptor
      a(nta)gonists. A combination of the design and generation of millions to billions
      of different ligands, together with phage display for the isolation of binding
      ligands and with functional assays for identifying (and possibly selecting) bio
      active ligands, will open even more challenging applications of this inspiring
      technology, and provide a powerful tool for drug and target discovery well into
      the next decade.

PMID- 9661811
TI  - Selection of phage displayed peptides from a random 10-mer library recognising a
      peptide target.
AB  - BACKGROUND: Peptide display libraries are powerful tools in the search for
      detailed information about protein-protein interactions. Usual targets for
      isolation of phage displayed peptide ligands include antibodies, various
      receptors, other full size proteins or larger fragments thereof. Smaller protein
      fragments such as synthetic peptides have not been reported as targets for
      screening of peptide display libraries. OBJECTIVES: To investigate whether a
      protein target used for screening of a peptide display library could be scaled
      down to peptide size. As the peptide target we wanted to use a sequence derived
      from the cytosolic tail of MHC class II associated invariant chain containing a
      leucine class endosomal sorting signal, known to be recognised as an autonomous
      functional unit during targeting of class II complexes to antigen processing
      compartments. STUDY DESIGN: A screening procedure where a synthetic 15-mer
      invariant chain peptide was coupled to a methacrylate matrix of high binding
      capacity was developed, and three rounds of selection were performed from a
      random 10-mer fUSE5 display library. RESULTS: The peptide display library was
      successfully enriched for phage clones with affinity for the invariant chain
      peptide. Furthermore, the binding phage clones were able to distinguish between a
      functional and a mutated form of the target. These clones therefore displayed
      possible peptide mimetics of signal recognition sites in the cellular sorting
      machinery. CONCLUSION: The size of a protein target may be scaled down to peptide
      size and be recognised by a 10-mer peptide displayed on filamentous phage. This
      approach may particularly be useful when the peptide target contains a functional
      unit for recognition.

PMID- 9661812
TI  - Immunoglobulin G abnormalities in HIV-1 infected individuals with lymphoma.
AB  - BACKGROUND: Polyclonal B-cell activation precedes the occurrence of malignant B
      cell clones. Several recent reports suggest a perturbed cytokine regulation in
      HIV-related lymphomagenesis and Epstein-Barr virus (EBV) involvement in
      approximately half of the cases with generalized lymphoma. OBJECTIVES: We
      investigated whether altered immunoglobulin properties would be detected by fine
      analysis of the immunoglobulin G (IgG) subclass patterns against HIV and EBV
      epitopes. STUDY DESIGN: HIV-1 infected patients in early stage, late stage and
      with lymphoma were analyzed by ELISA for anti HIV and EBV IgG class and subclass
      antibodies. Avidity and affinity of the antibodies were studied. The lymphoma
      patients were also studied by PCR for EBV DNA in serum. RESULTS: The total IgG
      reactivity to several HIV antigens was similar in the three patient groups.
      However, lymphoma patients had a more restricted subclass pattern with
      significantly lower IgG1 and IgG3 anti gp120 titers compared to other HIV
      infected patients but good and persistent total IgG and IgG1 (excluding the gp120
      antigen) reactivities in contradiction to their low CD4 counts. IgG4 reactivity
      was sparse, detectable to significant levels in the symptomatic group only. The
      observed relative affinity of the HIV-specific IgG and IgG1 of lymphoma patients
      was similar to that of asymptomatic and symptomatic patients. The subclass
      reactivity to the EBV peptide was similar in all groups but lymphoma patients
      with EBV DNA in serum exhibited significantly lower anti EBV peptide titers than
      those who were EBV DNA negative. CONCLUSION: These findings indicate that
      subclass analysis to defined viral antigens may be a means to detect immune
      dysregulation in tumor development.

PMID- 9661813
TI  - Variation in IgG1 heavy chain allotype does not contribute to differences in
      biological activity of two human anti-Rhesus (D) monoclonal antibodies.
AB  - BACKGROUND: Pooled human anti-Rhesus D antiserum is currently administered for
      the prevention of RhD alloimmunization. Increased demand, and decreased supply,
      of donated pooled antiserum has led to the investigation of the suitability of
      human monoclonal anti-RhD antibodies for use in its place. However, it is unclear
      which biological properties of monoclonal antibodies are important for function
      in RhD-positive foetal red cell clearance and the prevention of alloimmunization.
      Various antibodies behave differently in a number of in vitro assays of
      biological function. OBJECTIVES: To compare the function and structure of two
      human anti-RhD IgG1 monoclonal antibodies which differ in their ability to
      promote red cell lysis in vitro. In particular to examine whether the functional
      differences correlate to differences in the IgG1 heavy chain constant region
      (allotype). STUDY DESIGN: We report here the cloning, characterization and re
      expression in stable myeloma cell transformants of cDNAs coding for two such
      antibodies, secreted by the heterohybridoma cell lines ESD-1 (THERAD 03) and LHM
      70/45.3 (THERAD 06). The cDNAs were then recombined to exchange portions of the
      Fc encoding regions and the recombinant antibodies were assayed in vitro to
      determine RhD-positive red cell-dependent activity. RESULTS: Recombinant THERAD
      03 and 06 antibodies behaved identically to the parent antibodies. The 'inactive'
      THERAD 06 did not have biological activity reconstituted by exchange with the
      THERAD 03 Fc regions, nor was THERAD 03 activity abolished by the reciprocal Fc
      region exchange. CONCLUSIONS: Human monoclonal anti-RhD antibodies can be cloned
      and re-expressed in stable cell lines, and exhibit identical properties to the
      parent antibodies. Differences in biological activity cannot be attributed to
      differences in IgG1 heavy chain allotype.

PMID- 9661814
TI  - Kinetic and affinity constants of epitope specific anti-carcinoembryonic antigen
      (CEA) monoclonal antibodies for CEA and engineered CEA domain constructs.
AB  - BACKGROUND: Carcinoembryonic antigen (CEA) is a human tumor antigen with the
      domain structure N-A1-B1-A2-B2-A3-B3, in which each domain is predicted to have
      an Ig-like fold and is known to bind epitope specific anti-CEA antibodies.
      OBJECTIVE: To determine the affinity constants of several domain specific anti
      CEA antibodies using purified recombinant or synthetic domains. RESULTS AND
      CONCLUSION: We have determined the kinetic and affinity constants of several anti
      CEA antibodies for CEA, CEA domains (A3-B3) expressed in HeLa cells, and a
      synthetic peptide corresponding to the A3 domain using a BIAcore biosensor. There
      was no difference in affinity for CEA among a murine (mT84.66), a mouse/human
      chimeric form (cT84.66) or a disulfide deleted version (delta SScT84.66) of this
      antibody. There was less than a five-fold drop in affinity of murine T84.66 for
      the A3-B3 domain expressed in HeLa cells compared to CEA. The synthetic A3 domain
      had an affinity constant for mT84.66 which was ten-fold less than for CEA. The
      affinity constants for CEA with several other anti-CEA monoclonal antibodies,
      including three antibodies which have almost identical CDR sequences (CEA.281,
      CEA.11 and CEM231) were also determined. CEM231 which had a two-fold higher
      affinity constant for CEA than either CEA.281 or CEA.11 had a two-fold faster on
      rate which accounts for its higher affinity constant. This difference may be due
      to one or more of the amino acid differences present in H1 (N vs. S or D) and H3
      (A vs. V).

PMID- 9661815
TI  - Fine tuning of an anti-testosterone antibody binding site by stepwise
      optimisation of the CDRs.
AB  - BACKGROUND: We have previously reported specificity improvement of an anti
      testosterone monoclonal antibody (3-C4F5) by random mutagenesis of the third
      complementarity determining regions (CDR3s) and by phage display selection.
      OBJECTIVES: Here we extend the mutagenesis strategy to the other CDRs and select
      the mutant libraries using two different approaches in order to further fine-tune
      the binding properties of this recombinant Fab fragment. STUDY DESIGN: To improve
      the affinity the new mutant libraries were selected by using limiting, decreasing
      concentrations of biotinylated testosterone (TES) in solution and capturing the
      binders on streptavidin-coated microtiter plate. The specificity was improved by
      preincubating the mutant libraries in solution with a high concentration of the
      most problematic cross-reacting steroid, dehydroepiandrosterone sulfate (DHEAS).
      RESULTS: In two different light chain CDR1 mutant clones isolated from the
      affinity pannings, the relative TES affinity was increased over 10-fold while the
      cross-reactivities to related steroids were preserved at the same level as in the
      parental combined CDR3 mutant clone. New heavy chain CDR1 and light chain CDR2
      mutants showing slightly decreased cross-reactivities were isolated from
      specificity selections. By combining compatible mutant CDRs together we were able
      to create a Fab fragment with over 12-fold higher relative TES affinity and
      significantly lower cross-reactivity to DHEAS when compared to the original
      monoclonal antibody 3-C4F5. CONCLUSIONS: Our results demonstrate that a high
      affinity and selective recombinant Fab fragment working over a wide TES
      concentration range with clinical samples could be generated by CDR mutagenesis
      and phage display selection.

PMID- 9661816
TI  - Characterization of anti-mouse Fc gamma RII single-chain Fv fragments derived
      from human phage display libraries.
AB  - BACKGROUND: Few antibodies are available to study the function of the Fc gamma
      RII murine immunoglobulin receptor. Human phage display libraries represent a
      potential source of single-chain Fv (sFv) to facilitate the study of the Fc gamma
      RII murine immunoglobulin receptor. OBJECTIVES: To isolate human sFv specific for
      mouse Fc gamma RII. STUDY DESIGN: Two human phage display libraries were selected
      for reactivity to mouse Fc gamma RII. Those human anti-mouse Fc gamma RII sFv
      that were derived from the libraries were characterized with respect to kinetics,
      cellular binding, epitope specificity and amino acid sequence. RESULTS: Nine anti
      mouse Fc gamma RII sFv molecules were isolated from two human phage display
      libraries (Marks et al., J Mol Biol 1991;222:581-597; Sheets et al., Proc Natl
      Acad Sci USA, in press). Surface plasmon resonance (SPR) analysis revealed that
      the human anti-mouse Fc gamma RII sFv had off-rates ranging from 10(-2) to 10(-3)
      s-1, with KD values calculated to range between 10(-7) and 10(-9) M. The binding
      of the FITC-labeled human anti-mouse Fc gamma RII sFv to mouse peritoneal
      neutrophils was not detected by flow cytometry, due to the rapid off-rates of
      these monomeric proteins. However, when the human anti-mouse Fc gamma RII sFv
      were coated on yellow-green latex particles, all of the human sFv were found to
      specifically bind to mouse peritoneal neutrophils. Deglycosylation of mouse Fc
      gamma RII did not diminish the binding of these sFv, suggesting that the sFv
      molecules recognize a polypeptide epitope on murine Fc gamma RII. In contrast,
      denaturation of mouse Fc gamma RII dramatically reduced the binding of the human
      sFv, suggesting that the epitopes are conformational. Sequence analysis of the
      human anti-mouse Fc gamma RII sFv revealed a high degree of structural similarity
      among the nine sFv. The DP73 VH gene segment was utilized by four of the nine
      sFv, while seven of the nine sFv contained the DPL16 V lambda gene segment. The
      sequence similarities between these sFv suggested that several of the human sFv
      may recognize a common epitope on mouse Fc gamma RII. Epitope mapping studies
      demonstrated that eight of the nine human anti-mouse Fc gamma RII sFv recognized
      overlapping epitopes. All of these human anti-mouse Fc gamma RII sFv competed
      with the 2.4G2 rat monoclonal anti-mouse Fc gamma RII/III antibody for binding
      with mouse Fc gamma RII, suggesting that the targeted epitopes reside in or near
      the Fc binding pocket of mouse Fc gamma RII. CONCLUSIONS: The availability of
      novel sFv recognizing mouse Fc gamma RII will facilitate the study of receptor
      triggering events. Such sFv may prove useful to engage murine Fc gamma RII for
      targeted cytotoxicity or immunization strategies.

PMID- 9661817
TI  - Electronic monitoring of adherence to treatment in the preventive chemotherapy of
      tuberculosis.
AB  - SETTING: Non-adherence to treatment is a frequent problem in the preventive
      chemoprophylaxis of tuberculosis. OBJECTIVE: To evaluate the usefulness of the
      Medication Event Monitoring System (MEMS) for following and improving patient
      adherence to 6-month treatment with isoniazid. DESIGN: Three methods of
      monitoring compliance, MEMS, pill count and a urine test for isoniazid, were
      compared prospectively in 30 patients. The efficacy of a combined intervention by
      the physician and the pharmacist was evaluated in non-compliant patients.
      RESULTS: According to the MEMS data, overall adherence to isoniazid therapy was
      91.5%, and 86% of the patients were considered compliant throughout the period of
      observation. The pill count and the urine test tended to overestimate the overall
      compliance when compared to the MEMS. The combined intervention of the physician
      and pharmacist allowed drug adherence to be enhanced in non-compliant patients,
      but the effect was only transient if this was not repeated every month.
      CONCLUSION: Our results suggest that the MEMS system is a useful approach for
      monitoring and improving compliance with preventive chemotherapy for
      tuberculosis.

PMID- 9661818
TI  - Cost-effectiveness of directly observed chemoprophylaxis of tuberculosis among
      drug users at high risk for tuberculosis.
AB  - SETTING: A methadone treatment program with on-site medical care in the Bronx,
      New York. OBJECTIVE: To define whether costs associated with directly observed
      preventive therapy (DOPT) of tuberculosis are justified by cases and costs of
      tuberculosis prevented among persons at high risk for active disease. DESIGN:
      Detailed data were collected on drug users in treatment regarding human
      immunodeficiency virus (HIV) and tuberculosis infection and disease, and costs of
      screening, chemoprophylaxis, direct observation and treatment of active disease.
      The cost-effectiveness of providing DOPT to this population was modeled. RESULTS:
      We assessed the impact of providing DOPT to 151 eligible persons. Assuming 65%
      isoniazid effectiveness, and incorporating costs of screening, observed
      chemoprophylaxis and clinical monitoring, a net savings in tuberculosis-related
      hospital costs of $285,284 ($563 per person screened) was associated with DOPT
      ($10,274 per case prevented). Direct observation of chemoprophylaxis proved cost
      effective if associated with even a 10% increment in overall isoniazid
      effectiveness compared with self-administered chemoprophylaxis. DOPT costs per
      tuberculosis case averted remained below the in-patient costs of a single case of
      drug-sensitive disease across a range of parameter values. CONCLUSIONS: Providing
      DOPT is a highly cost-effective intervention for drug users in treatment.
      Commitment of additional resources required for DOPT should be given priority in
      this and other populations at high risk for tuberculosis.

PMID- 9661819
TI  - MPB64 mycobacterial antigen: a new skin-test reagent through patch method for
      rapid diagnosis of active tuberculosis.
AB  - SETTING: A collaborative study between the Japan BCG Laboratory, Tokyo, Japan,
      and the Infectious Disease Section, Philippine General Hospital, Manila, the
      Philippines. Tuberculosis patients from four clinics in the vicinity of Manila,
      Our Lady of Grace Parish, Sto. Nino de Tondo Parish, the Canossa Health and
      Social Center, and the Health Care Development Center, were examined. OBJECTIVE:
      To develop a new, simple and rapid diagnostic method for active tuberculosis.
      Subjects were tested for skin reaction to a special antigen, MPB64, by the patch
      test method instead of intradermal injection of purified protein derivative
      (PPD). DESIGN: Fifty-three active tuberculosis patients and 43 healthy PPD
      positive controls were tested to determine whether or not the reaction to MPB64
      was positive only in active tuberculosis patients. RESULTS: Fifty-two of the 53
      active tuberculosis patients showed a positive reaction to MPB64, while none of
      the 43 PPD-positive controls did. The specificity of MPB64 to active tuberculosis
      was 100%, and the sensitivity was 98.1%. The efficacy of the test was 98.9%.
      CONCLUSION: The patch test with MPB64 is a promising method for the diagnosis of
      active tuberculosis, distinguishing tuberculous patients from those who are
      infected but have not developed the disease, and also from BCG-vaccinated
      individuals. This new skin test is a subject for further evaluation and it is
      important to compare the results with PPD Mantoux.

PMID- 9661820
TI  - Impact of human immunodeficiency virus infection on the outcome of treatment and
      survival of tuberculosis patients in Mwanza, Tanzania.
AB  - SETTING: Little is known about the outcome of tuberculosis (TB) treatment and
      subsequent survival of human immunodeficiency virus (HIV) infected patients
      treated under routine programme conditions in a developing country. We followed a
      cohort of HIV-positive and HIV-negative tuberculosis patients during therapy and
      assessed their vital and tuberculosis status 3 years after completion of
      treatment in Mwanza, Tanzania. METHODS: Newly diagnosed and relapse tuberculosis
      cases consecutively registered over a 6-month period were enrolled into an
      epidemiological study of TB/HIV. Treatment outcome was based on information in
      tuberculosis treatment registers. Patients surviving treatment were assessed 3
      years later by personal interview. Cause of death was determined by verbal
      autopsy. RESULTS: Of 561 patients enrolled into the study, 505 patients alive at
      completion of treatment were eligible for assessment at 3 years. Except for
      mortality, HIV infection was not statistically associated with differing
      treatment outcomes. At time of follow-up, the overall mortality was 19% and was
      associated with HIV infection (hazard ratio [hr] 3.7, 95% confidence interval
      [CI] 2.6-5.2) and age 35 years and over (hr 1.5, 95% CI 1.02-2.1), but not with
      type of tuberculosis, gender, or initial drug resistance. By life table analysis,
      probability of survival at 4 years was 35% for HIV-positive patients compared to
      90% for HIV-negative patients. Although no relapse cases were diagnosed, verbal
      autopsy suggested equivalent low rates of relapse in both groups. CONCLUSION:
      These results demonstrate the effectiveness of the current approach to the
      treatment of tuberculosis patients regardless of HIV status. However, HIV-related
      mortality remains high both during and following completion of treatment, and
      further studies are needed to determine if this mortality might be reduced by
      simple interventions which are feasible in developing countries.

PMID- 9661821
TI  - Tuberculous meningitis in adults: an eleven-year review.
AB  - OBJECTIVE: To assess the presentation, diagnosis and outcome of patients with
      tuberculous meningitis (TBM). DESIGN: The medical records of adults with TBM who
      were treated at Dicle University Hospital between January 1985 and October 1996
      were reviewed. RESULTS: In total, 101 patients were identified and stratified
      according to the stage of disease at presentation. The mean duration of the
      symptoms of TBM before admission was 12 days. The majority of patients had
      headaches (96.0%), fever (91.1%), nuchal rigidity (91.1%), vomiting (81.2%),
      meningism (79.2%) and abnormal mental state (72.3%). The mean cerebrospinal fluid
      (CSF) leukocyte count was 0.38 x 10(9)/L, protein 1410 mg/L, glucose 2.0 mmol/L
      and CSF/blood glucose ratio 27%. Cranial computerized tomography (CT) scans were
      performed during the course of TBM in 64 patients. The results were normal in
      6.3%, and abnormal in 93.7% of the cases; the most frequent abnormality found on
      CT was hydrocephalus (45.3%). Forty-four patients (43.5%) died. Minor
      neurological sequelae developed in 11 patients (10.9%), major sequelae in 10
      (9.9%), and 31 patients (30.7%) completely recovered. There was no follow-up for
      five patients (5.0%). Five factors were important in predicting fatal outcome:
      stage III at presentation, low glucose levels, low CSF/blood glucose ratio, high
      protein levels, and CT scanning abnormality. CONCLUSION: TBM is a very critical
      disease in terms of fatal outcome and permanent sequelae: 43.5% of the patients
      died and only 30.7% experienced complete recovery. Early treatment may reduce
      fatal outcome and morbidity.

PMID- 9661822
TI  - Diagnostic features and therapeutic outcome of erosive and ulcerous endobronchial
      tuberculosis.
AB  - SETTING AND OBJECTIVE: Erosive and ulcerous endobronchial tuberculosis (EBTB) is
      distinct from pulmonary tuberculosis in some aspects. We evaluated the clinical
      features of 56 patients (26 males and 30 females) with EBTB to characterize the
      clinical features of the disease. RESULTS: The chief complaint in 70% of patients
      was intractable cough, particularly in those with tracheal tuberculosis. The
      predominant radiological features were patchy bi-apical infiltrates of variable
      intensity without cavitation; for six patients, however, plain radiographs
      revealed no abnormalities. The ulcerous lesions could be classified into three
      stages: active, healing and scarring. Furthermore, we divided scarring stage into
      two subtypes, polypoid and non-polypoid. Most of the patients were treated with
      isoniazid, rifampin, and streptomycin (SM) or ethambutol. Approximately one-third
      of the patients, not randomly selected, were treated with aerosolized SM and
      corticosteroids in addition to conventional oral therapy. CONCLUSION: EBTB
      involves typical clinical and radiographic features. In this uncontrolled series,
      it was our impression that the period of time to healing of ulcerous lesions
      seemed to be shorter in those treated with aerosol therapy including streptomycin
      and corticosteroids.

PMID- 9661823
TI  - Abdominal tuberculosis in Qatar: a clinico-radiological study.
AB  - SETTING: Hamad General Hospital, the tertiary health centre for Doha, Qatar.
      OBJECTIVE: The purpose of the study was to define and correlate the role of
      radiology with clinical and pathological findings in abdominal tuberculosis.
      MATERIAL AND METHODS: A total of 59 patients (47 males and 12 females) diagnosed
      bacteriologically and/ or histologically for abdominal tuberculosis were
      radiologically assessed. Evaluation was based on the analysis of plain abdominal
      radiographs, gastro-intestinal contrast studies (barium meal follow through and
      barium enema), ultrasonography and computed tomography. RESULTS: Plain abdominal
      radiographs performed in 38 patients were positive in 19 cases (50%).
      Gastrointestinal contrast examinations were positive in 27 out of 34 cases (80%).
      Ultrasound examinations were abnormal in 25 out of 31 cases (81%), while computed
      tomography, performed in 24 patients, revealed abnormal findings in 19 cases
      (80%). Combined radiographic and imaging procedures revealed peritoneal
      involvement (ascites) in 16 patients (27%), bowel involvement in 36 (61%), mass
      lesion in 11 (19%), lymphadenopathy in 13 (22%) and organ involvement in 13
      (22%). CONCLUSION: There was no single radiological method that provided all
      necessary information suggestive of abdominal tuberculosis. Although unequivocal
      diagnosis of abdominal tuberculosis can only be made by culture and histological
      findings, combined computed tomography and ultrasound findings were the most
      important imaging tools in the diagnostic process for abdominal tuberculosis,
      while contrast studies helped to assess the extent of bowel disease, hence
      influencing decisions concerning surgery.

PMID- 9661824
TI  - The changing pattern of intestinal tuberculosis: 30 years' experience.
AB  - SETTING: Although the incidence of tuberculosis had been decreasing for many
      years, it has recently risen. OBJECTIVES: To investigate the changes in the
      pattern and distribution of intestinal tuberculosis and to alert surgeons to the
      importance of maintaining a high index of suspicion for this disease entity.
      DESIGN: Retrospective analysis of 134 patients with intestinal tuberculosis
      discharged from the Veterans General Hospital in Taipei from 1965 to 1995. All
      records, bacteriological examinations and pathological specimens were reviewed
      and extracted onto a standard questionnaire. RESULTS: A decline in the case
      numbers of intestinal tuberculosis was noted after 1975. However, there seems to
      be a slight rise in case numbers since 1990. The average age of those patients
      after 1990 (64.8 years) is higher than those before 1990 (44.4 years). None of
      our patients had clinical signs of human immunodeficiency virus (HIV) infection.
      Most patients (81.3%, 109/134) had not received a definite diagnosis until
      surgery. Active pulmonary tuberculosis was found in 37 patients (29.1%).
      CONCLUSION: The possible reasons for the rise in cases of intestinal tuberculosis
      in our patients may be linked to an increased life expectancy, the reappearance
      of some formerly 'silent' tuberculosis cases, and relapse in patients having
      received incomplete antituberculosis chemotherapy. Its insidious and non-specific
      clinical presentation makes the diagnosis of intestinal tuberculosis difficult.
      An increased index of suspicion and greater familiarity with the disease may
      shorten the time of diagnosis and may also prevent some unnecessary operations.

PMID- 9661825
TI  - Hepatosplenic tuberculosis: a cause of persistent fever during recovery from
      prolonged neutropenia.
AB  - SETTING: Hepatosplenic abscesses in neutropenic patients, especially during the
      recovery phase, are almost always attributed to fungal infections. We report
      similar lesions due to Mycobacterium tuberculosis in neutropenic patients in a
      tertiary care centre in India. OBJECTIVE: To characterize the features of
      hepatosplenic tuberculosis in neutropenic patients. DESIGN: Retrospective
      comparison of disease pattern and response to treatment of hepatosplenic
      tuberculosis in febrile neutropenia patients (four of 30 with severe prolonged
      neutropenia) and in non neutropenic patients diagnosed during the same 12-month
      period (n = 4, control group). RESULTS: The disease in the neutropenic patients
      typically presented during the recovery phase of neutropenia, with ultrasonic
      abnormalities similar to those seen in hepatosplenic fungal infections. In
      contrast to the marked organomegaly and typical granulomatous response found in
      the control group, the disease in the neutropenic patients was characterised by
      an absence of organomegaly, non-involvement of other sites, poor inflammatory
      response and a high bacillary load. The initial response to therapy was
      satisfactory in both groups. CONCLUSION: Tuberculosis needs to be considered in
      the diagnostic work-up of hepatosplenic abscesses that occur during the recovery
      phase of neutropenia.

PMID- 9661826
TI  - Drug resistance in Mycobacterium tuberculosis strains isolated from re-treatment
      cases of pulmonary tuberculosis in Ethiopia: susceptibility to first-line and
      alternative drugs.
AB  - SETTING: Addis Ababa Tuberculosis Demonstration and Training Center, Ethiopia.
      OBJECTIVES: To determine the pattern of drug resistance among re-treatment cases
      of pulmonary tuberculosis (TB), to determine the risk factors associated with
      multi-drug resistant (MDR) TB, and to propose re-treatment regimens based on the
      patterns of susceptibility to first-line and alternative drugs. DESIGN: One
      hundred and seven Mycobacterium tuberculosis strains isolated from an equal
      number of re-treatment cases of pulmonary TB were included in the study. Drug
      susceptibility was determined by the Bactec method. RESULTS: About 50% of the
      strains were resistant to one or more of the first-line drugs and 12% of the
      strains were multi-drug resistant, i.e., resistant to both isoniazid and
      rifampicin. Previous treatment with rifampicin was the most important predictor
      of MDR-TB. All MDR strains were susceptible to amikacin, ciprofloxacin,
      ethambutol, ethionamide and clofazimine. CONCLUSION: The WHO re-treatment regimen
      would theoretically be effective for the treatment of all non-MDR-TB patients in
      this study. A proposed 12-month re-treatment regimen for MDR-TB patients would
      include a fluoroquinolone in combination with streptomycin, pyrazinamide,
      isoniazid, ethambutol and clofazimine. There is an urgent need for more research
      to define safe and inexpensive treatment regimens for MDR-TB patients in low
      income countries.

PMID- 9661827
TI  - Molecular analysis of rifampin-resistant Mycobacterium tuberculosis isolated from
      Korea by polymerase chain reaction-single strand conformation polymorphism
      sequence analysis.
AB  - OBJECTIVE: To assess the molecular mechanism of rifampin (RMP) resistance in
      clinical strains of Mycobacterium tuberculosis. DESIGN: The molecular nature of a
      part of the rpoB gene in 77 M. tuberculosis clinical strains isolated in Korea
      was analyzed using polymerase chain reaction-single strand conformation
      polymorphism (PCR-SSCP) and PCR-sequence analysis. RESULTS: Among 67 RMP
      resistant isolates, 50 showed SSCP profiles different from that of an RMP
      sensitive control strain, M. tuberculosis H37Rv, indicating the possible
      existence of a sequence alteration in this region of the rpoB gene, while 17
      resistant isolates displayed SSCP profiles indistinguishable from that of the
      sensitive control strain. Subsequently, 17 clinical isolates whose SSCP profiles
      were difficult to distinguish from the control strain were subjected to sequence
      analysis. The analysis revealed that all 17 isolates did indeed contain mutations
      in the 81 bp region of the rpoB gene, which is associated with RMP resistance.
      CONCLUSION: The results from our study clearly indicate that the molecular
      mechanism of RMP resistance in M. tuberculosis isolates from Korea involves
      alterations in the rpoB gene. In addition, this study suggests that PCR-direct
      sequence analysis works more efficiently and accurately than PCR-SSCP analysis
      for rapid screening of RMP-resistant M. tuberculosis clinical isolates.

PMID- 9661828
TI  - Influence of antimicrobial chemotherapy and smoking status on the plasma
      concentrations of vitamin C, vitamin E, beta-carotene, acute phase reactants,
      iron and lipid peroxides in patients with pulmonary tuberculosis.
AB  - SETTING: Inflammation-related oxidative stress has been implicated in the
      pathogenesis of lung fibrosis and dysfunction in patients with pulmonary
      tuberculosis. OBJECTIVE: To investigate the effects of antimicrobial chemotherapy
      and smoking status on the plasma concentrations of the anti-oxidative nutrients
      vitamin C, vitamin E and beta-carotene, as well as those of iron, lipid peroxides
      and the acute phase reactants C-reactive protein (CRP) and ferritin. DESIGN: A
      total of 41 patients with active pulmonary tuberculosis were studied at the
      outset and after 6 months of antimicrobial chemotherapy. RESULTS: Initial plasma
      concentrations of vitamin C and beta-carotene were low, returning to normal
      values after chemotherapy in the non-smokers, but not in the smokers, while those
      of vitamin E remained low throughout in both groups. Ferritin and CRP
      concentrations decreased significantly following chemotherapy, with the former
      higher in smokers than in non-smokers. Serum lipid peroxides were elevated in
      patients with pulmonary tuberculosis and were unaffected by chemotherapy or
      smoking habits, while iron levels were not significantly affected by
      chemotherapy. Although residual dysfunction and infiltration were evident,
      pulmonary function (FEV1) and radiographic score improved equally in both smokers
      and non-smokers following antimicrobial chemotherapy. CONCLUSIONS: Even after 6
      months of apparently successful antimicrobial chemotherapy, pulmonary
      tuberculosis is associated with increased oxidative stress, which is unrelated to
      cigarette smoking and characterized by increased levels of circulating lipid
      peroxides and low concentrations of plasma vitamin E.

PMID- 9661829
TI  - Clinical features of non-tuberculous mycobacterial disease: comparisons between
      smear-positive and smear-negative cases, and between Mycobacterium avium and
      Mycobacterium intracellulare.
AB  - OBJECTIVE: To evaluate the differences in clinical symptoms and radiological
      findings between smear-positive non-tuberculous mycobacteria (NTM) and smear
      negative, culture-positive NTM. Also, to evaluate the differences in clinical
      symptoms and radiological findings between Mycobacterium avium and M.
      intracellulare. DESIGN: A retrospective study was performed of 200 cases with
      positive pulmonary cultures for NTM between January 1989 and December 1996. It
      was determined whether or not pulmonary disease was caused by NTM using the 1990
      criteria recommended by the American Thoracic Society. Clinical symptoms and
      radiological findings were compared between groups. RESULTS: Fever and hemoptysis
      were more frequently observed in smear-positive patients (26/50, 52%, and 24/50,
      48%, respectively) than in smear-negative, culture-positive patients (8/38,
      21.1%, P < 0.005, 8/38, 21.1%, P < 0.01, respectively). In addition, cavity
      formation was more frequently observed in chest computed tomography scans of
      smear-positive patients (19/36, 52.8%) than in smear-negative patients (6/31,
      19.4%, P < 0.005). Finally, cavity formation tended to be more frequently
      observed with M. avium than with M. intracellulare. CONCLUSION: The present study
      demonstrates differences in clinical symptoms and radiological findings between
      smear-positive and smear-negative NTM cases, as well as between M. avium and M.
      intracellulare.

PMID- 9661830
TI  - Acute liver failure caused by isoniazid in a child receiving carbamazepine.
AB  - We report a case of a 10-year-old boy, being treated for seizures with
      carbamazepine, who developed acute liver failure within four days of initiation
      of therapy for suspected tuberculosis with isoniazid, rifampin, pyrazinamide, and
      ethambutol. Isoniazid-induced liver disease was diagnosed. The likely role of
      carbamazepine and rifampin in potentiating the hepatotoxicity of isoniazid, and
      the importance of early recognition of isoniazid-induced liver disease, are
      discussed.

PMID- 9661831
TI  - Only one-third of US adults can correctly identify how tuberculosis is spread.

PMID- 9661832
TI  - Immunization of common marmosets with Epstein-Barr virus (EBV) envelope
      glycoprotein gp340: effect on viral shedding following EBV challenge.
AB  - Epstein-Barr virus (EBV), the cause of infectious mononucleosis, is involved in
      the pathogenesis of several human cancers, the highest frequency of association
      being found in undifferentiated nasopharyngeal carcinoma and endemic Burkitt's
      lymphoma. The development of animal models in which potential vaccines can be
      tested is important. EBV infection of the common marmoset, using the M81 strain
      originally derived from a patient with nasopharyngeal carcinoma, induces a
      carrier state in this animal. Persistent infection is characterized by the
      production of antibodies to viral antigens, and the secretion of EBV DNA into
      buccal fluids. Following immunization with envelope glycoprotein gp340 derived
      from a bovine papilloma virus expression vector, prior to EBV infection, viral
      DNA was detected significantly less frequently in the buccal fluids of immunized,
      than of nonimmunized, infected animals, indicating that although the carrier
      state had not been abolished, it had been altered. A reduction in virus load was
      also observed when offspring of seronegative, and on occasion seropositive,
      parents were immunized neonatally, before EBV challenge.

PMID- 9661834
TI  - Human cytomegalovirus infection induces mRNA expression and secretion of
      plasminogen inhibitor type-1 in endothelial cells.
AB  - The aim of the study was to investigate whether infection of endothelial cells
      with human cytomegalovirus (HCMV) perturbs expression and production of
      plasminogen activator inhibitor type-1 (PAI-1). mRNA expression of PAI-1 was
      investigated by isolating total RNA from HCMV-infected and control cells,
      followed by Northern blotting and probing with 32P-labelled PAI-1 probe. Sandwich
      ELISA was used to investigate PAI-1 production. HCMV induced the expression of
      PAI-1-mRNA at 2-5 days postinfection (maximum expression was at 3 days
      postinfection which was 40% higher than control). HCMV also induced secretion of
      PAI-1 at 2-5 days postinfection. These results indicate that infection of
      endothelial cells with HCMV disturbs PAI-1 expression and production in these
      cells.

PMID- 9661833
TI  - Prevalence of papillomavirus, Epstein-Barr virus, cytomegalovirus, and herpes
      simplex virus type 2 in urinary bladder cancer.
AB  - Recent epidemiological studies suggest that the risk for urological malignancies
      may be related to the exposure to infectious agents. Human Papillomaviruses type
      16 and 18 (HPV 16, HPV 18), Epstein-Barr virus (EBV), cytomegalovirus (CMV) and
      herpes simplex virus type 2 (HSV-2) have been suggested previously as cofactors
      in the pathogenesis of some malignancies in humans. The present paper, the
      presence of HPV 16, HPV 18, EBV, CMV and HSV-2 genomes was investigated in a
      panel of 35 biopsies from urinary bladder carcinomas using the polymerase chain
      reaction (PCR). Sequences of EBV, HPV, CMV and HSV-2 genomes were detected in
      34%, 31%, 11% and 9% of tissue samples respectively, while in 20% of patients we
      found more than one viral infection. Absence of viral genomes was found in normal
      bladder. To our knowledge, this is the first report concerning the association of
      EBV, CMV and HSV-2 with bladder cancer. This finding may raise the question
      whether such viral infection may contribute to development and progression of
      some types of urological malignancies in humans.

PMID- 9661835
TI  - Antibody response to human cytomegalovirus (HCMV) glycoprotein B (gB) in AIDS
      patients with HCMV end-organ disease.
AB  - Human cytomegalovirus (HCMV)-specific antibody responses in HIV-1 infected
      individuals either with or without HCMV end-organ disease were examined to
      determine the whether development of HCMV disease was associated with a
      particular deficit in the antibody response. Antiwhole HCMV, anti-glycoprotein B
      (gB), and neutralizing antibody levels were higher in HIV-1 infected individuals
      than in healthy immunocompetent subjects, particularly in patients with AIDS
      either with or without HCMV-associated disease. Irrespective of location and
      spread of HCMV disease, patients who had received anti-HCMV therapy prior to
      sampling exhibited significantly higher anti-gB and neutralizing antibody titers
      than those who remained untreated. Likewise, patients with HCMV disease who were
      antigenemic or viremic had significantly lower anti-gB and neutralizing antibody
      titers than those who tested negative in either assay. Patients with untreated
      HCMV disease had significantly lower antibody titers than AIDS patients without
      disease. Analysis of the IgG subclass antibody responses to gB revealed no
      significant differences among HIV-1 infected individuals. These results suggest
      that levels of detectable anti-gB and HCMV neutralizing antibodies are inversely
      related to systemic viral load. Thus, antibodies with such specificities may be
      relevant in preventing the establishment of HCMV-associated disease or in
      modulating its progression.

PMID- 9661836
TI  - Mapping of linear antigenic determinants on glycoprotein C of herpes simplex
      virus type 1 and type 2 recognized by human serum immunoglobulin G antibodies.
AB  - Using membrane-based dekapeptides, the reactivity of human serum antibodies with
      linear antigenic determinants of herpes simplex virus (HSV) type 1 and type 2
      glycoprotein C (gC-1, gC-2) was studied by pep scan and immunodot assay. The
      entire coding sequences of gC-1 and gC-2 were screened for the presence of linear
      epitopes by pep scan. Peptides recognized in an HSV-1 type-specific manner were
      mainly identified within the N-terminal third and at the C-terminus of gC-1,
      whereas most type-common antibodies were directed against colinear peptides
      within the central parts of gC-1 and gC-2. The type-specific reaction of human
      sera with gC-2 peptides in pep scan was poor. Eight peptides identified as
      immunoreactive by pep scan were further tested in immunodot assay for their
      reactivity with a human serum panel. None of the eight HSV-negative sera gave
      positive results by immunodot assay. Positive reactions with gC peptides were
      found to be strongly age-dependent, i.e., the rate of positive reactions was
      significantly higher in HSV-positive adults than in HSV-positive children.
      Antibody reactivity with two type-common gC peptides was demonstrated in 17 out
      of 28 HSV-positive sera. A putative type-specific gC-2 peptide employed in
      immunodot assay was inconsistently recognized by human sera. Twenty HSV-positive
      sera reacted with at least 1 of 5 type-specific gC-1 peptides. Nine sera showing
      no reactivity with glycoprotein G of HSV-1 (gG-1) by immunobloting recognized
      type-specific gC-1 peptides in immunodot assay. Thus, gC-1 peptides might allow
      the detection of HSV-1-specific antibodies in individuals showing no reactivity
      with commonly employed HSV-1-specific diagnostic antigenes, i.e., purified or
      recombinant gG-1.

PMID- 9661837
TI  - Prevalence of enteric viruses in human immunodeficiency virus seropositive
      patients in Venezuela.
AB  - The prevalence of enteric viruses associated with gastroenteritis was determined
      in 125 stool samples from patients infected with the human immunodeficiency virus
      (HIV), with or without diarrhea. Diagnostic assays included enzyme immunoassays
      for the identification of rotavirus, adenovirus, and Norwalk virus;
      polyacrylamide gel electrophoresis for atypical rotaviruses and picobirnaviruses
      and polymerase chain reaction for astrovirus. Enteric viruses were detected in
      6.4% (8 of 125) of the stools collected: five (4.0%) samples positive for
      adenoviruses, and three (2.3%) samples positive for picobirnaviruses were
      detected. No rotavirus, astrovirus, or Norwalk virus were observed. Only one of
      the viruses identified (adenovirus) was found in a sample from a patient with
      diarrhea. Viruses were detected in 10% of the patients with AIDS, 14% of the
      symptomatic patients, and none of the asymptomatic persons. These results do not
      support a major role for enteric viruses in the diarrhea suffered by HIV-infected
      patients.

PMID- 9661838
TI  - Prevalence and genotypes of GB virus C/hepatitis G virus (GBV-C/HGV) and
      hepatitis C virus among patients infected with human immunodeficiency virus:
      evidence of GBV-C/HGV sexual transmission.
AB  - The development of new antiretroviral agents may improve survival of HIV-infected
      individuals, and therefore chronic viral hepatitis may become more relevant in
      these patients. The presence of GBV-C/HGV and hepatitis C virus (HCV) RNA were
      investigated by reverse transcriptase-nested polymerase chain reaction in plasma
      from 168 Spanish HIV-infected patients belonging to four different risk groups:
      intravenous drug users (IVDUs), hemophiliacs, homosexuals, and heterosexuals. GBV
      C/HGV-RNA and HCV-RNA were detected in 18% and 43% of the patients, respectively.
      The prevalence of current infection with these viruses was notably high, 19% for
      GBV-C/HGV and 69% for HCV, among individuals with parenteral risk of infection
      (intravenous drug abusers and hemophiliacs), but sexual transmission with GBV
      C/HGV was also suggested because 16.5% of patients with sexual risk, either
      homosexual or heterosexual, had GBV-C/HGV-RNA in plasma. Although investigation
      of GBV-C/HGV-RNA possibly underestimates the actual prevalence of infection with
      GBV-C/HGV, the above data suggest that sexual contact may play a relevant role in
      the spread of this virus. Phylogenetic analysis showed no evidence for clustering
      of NS3 sequences into different genotypes or subtypes of GBV-C/HGV.

PMID- 9661839
TI  - Identification of a novel strain of hepatitis E virus responsible for sporadic
      acute hepatitis in Taiwan.
AB  - Hepatitis caused by the hepatitis E virus (HEV) is a self-limited disease and
      occurs most frequently as epidemic or sporadic hepatitis in developing countries.
      The role of HEV in sporadic acute hepatitis in areas without a history of
      hepatitis E epidemics is obscure. Recently, it was found that more than 10% of
      the patients with acute non-A, non-B, non-C hepatitis in Taiwan were associated
      with an acute HEV infection. Nucleotide sequences of the regions within the first
      open reading frame of HEV were determined in four cases and were 96.7-100%
      identical to each other. As compared to the isolates from China, Pakistan, Burma,
      India, Africa, and Mexico, the similarities were, however, only 71.7-79.3%.
      Phylogenetic analysis revealed that the four Taiwan isolates were categorized as
      a novel HEV group (the Taiwan strain), which was distinct from all of the strains
      isolated from other parts of the world. In addition, the isolates from China,
      Burma, India, and Pakistan were catalogued as the second genotype of HEV (the
      Asian strain), and the Mexican isolate as the third (the Mexican strain). The
      African isolate was more related to the Asian type and might be a subtype of the
      Asian strain. A simple genotyping method by polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) is described. The findings also support
      the hypothesis that HEV may be responsible for some sporadic acute non-A, non-B,
      non-C hepatitis in other developed countries.

PMID- 9661840
TI  - Measles virus RNA is not detected in inflammatory bowel disease using hybrid
      capture and reverse transcription followed by the polymerase chain reaction.
AB  - Recent epidemiological and immunohistochemical studies have indicated a possible
      link between measles virus and inflammatory bowel disease (IBD). The aim of this
      study was to use a sensitive and robust method for the detection of measles virus
      RNA in IBD and control clinical samples. Peripheral blood mononuclear cells and
      intestinal resection tissue from IBD and control patients were studied. Two
      methods were used to determine the presence of measles virus RNA: hybrid capture,
      using measles virus-specific oligonucleotides linked to paramagnetic solid-phase
      supports, was carried out on total cellular RNA to enrich for measles virus RNA
      sequences. Reverse transcription followed by the polymerase chain reaction (RT
      PCR) using rTth DNA polymerase was employed for amplification of measles virus N
      gene sequences amongst the enriched species. Total RNA was also used for RT-PCR
      of a housekeeping mRNA species to assess RNA quality. RT-PCR for another region
      of the measles genome (the haemagglutinin (H) gene) was also undertaken in order
      to confirm the results obtained using N-gene primers for analysis of these
      samples. None of the samples were positive for measles N- or H-gene RNA using RT
      PCR. Positive control samples confirmed the sensitivity of the methods employed.
      These results show that either measles virus RNA was not present in the samples,
      or was present below the sensitivity limits known to have been achieved.

PMID- 9661841
TI  - Small round-structured (Norwalk-like) viruses and classical human caliciviruses
      in southeastern Australia, 1980-1996.
AB  - A total of 6,226 fecal samples collected from 1980 to 1996 in the Australian
      states of Victoria, New South Wales, and Tasmania from individuals with
      gastroenteritis were tested for small round-structured viruses (SRSVs) and
      classical human caliciviruses (ClHuCVs) by electron microscopy. There were 223
      samples positive for SRSVs, and nine positive for ClHuCVs. SRSVs were detected in
      individuals of all ages and were commonly associated with gastroenteritis
      outbreaks in nursing homes and hospitals. SRSVs were detected throughout the
      year, but were more common in the period from late winter to early summer in
      Australia (August to December). There were peaks of virus activity in the early
      1980s and more recently in 1995 and 1996. Analyses by RT-PCR and sequencing of a
      segment of ORF1 encoding the putative RNA polymerase for SRSVs and ClHuCVs showed
      the presence of viruses belonging to several genogroups. Viruses of genogroup 1
      (Norwalk/Southampton-like) and genogroup 3 (ClHuCVs) were relatively rare.
      Viruses of genogroup 2 (Snow Mountain-like) were common, and could be divided
      into two subgroups, one containing Toronto/Mexico-like viruses, the other
      Lordsdale/Camberwell-like viruses. The majority of viruses detected belonged to
      this latter subgroup.

PMID- 9661842
TI  - Retrospective serological and genetic study of the distribution of hantaviruses
      in Greece.
AB  - A retrospective serological and genetic study of hantaviruses responsible for
      hemorrhagic fever with renal syndrome (HFRS) in Greece during the last 17 years
      is presented. Fifty-one serum samples taken from 30 HFRS cases previously
      diagnosed by immunofluorescence assay were tested by ELISA for IgG (Hantaan,
      Dobrava, and Puumala) and IgM antibodies (Hantaan and Puumala). Results were
      compatible with the majority of infections being related to hantaviruses carried
      by rodents of the subfamily Murinae. RNA was extracted from 26 selected samples
      and reverse transcriptase-polymerase chain reaction (RT-PCR) was performed using
      primers specifically designed for the detection of hanta-viruses associated with
      murine (MS-N-specific, MM-G1-specific primers) or arvicoline rodents (PPT-N
      specific primers). In addition, primers previously designed for the detection of
      the G2 coding region of the Murine-associated hanta-viruses were also used.
      Sequencing of the PCR products was then performed, followed by phylogenetic
      analysis of nucleotide sequence differences. Eleven out of the 26 serum samples
      tested were found to be positive by PCR with the MS-N primers, whereas four were
      positive with the MM-G1 primers, and only two with the G2 primers. None of the
      samples was found positive with the PPT primers. The sequence analysis showed
      that the virus that was responsible for these 11 HFRS cases was the Dobrava
      virus, which is endemic throughout the Balkans.

PMID- 9661843
TI  - The evolution of orthopaedic management of myelodysplasia.

PMID- 9661844
TI  - Sacral-level myelomeningocele: long-term outcome in adults.
AB  - We reviewed long-term outcome of 46 adult patients with sacral-level
      myelomeningocele with an average age of 23 years (range, 18-38). Data were
      collected from the medical records, computerized database, and a questionnaire.
      Thirty patients had high sacral lesions (weak gluteus medius, gluteus maximums,
      and gastroc/soleus), and 16 had low sacral lesions (fair to normal-strength
      gluteus medius, gluteus maximus, and gastroc/soleus). Thirteen patients had signs
      of tethered-cord syndrome, and 12 underwent neurosurgical release. Thirty-nine
      patients underwent a total of 217 orthopaedic surgeries. At the final follow-up,
      41 (89.13%) patients were community ambulators. Thirty-two required no external
      support for walking. Twenty-nine patients used some kind of orthosis. Aggressive
      management of tethered-cord syndrome, surgical correction of musculoskeletal
      deformities, and avoidance of arthrodesis at the foot level may be the main
      factors in accounting for these results.

PMID- 9661845
TI  - Valgus knee stress in lumbosacral myelomeningocele: a gait-analysis evaluation.
AB  - Twenty-five independent community-ambulating patients with lumbosacral-level
      myelomeningocele (N = 50 limbs) underwent gait analysis. The limbs of these
      patients were divided into two groups based on thigh-foot angle (TFA): Group I (n
      = 20) had marked external tibial torsion, TFA > or = 20 degrees, and group II had
      TFA between 10 and 20 degrees. Ten limbs were excluded because of neutral or
      internal alignment. Twenty normal limbs with TFA = 10 degrees served as controls.
      An abnormal internal varus knee stress during stance was identified in all group
      I limbs and 12 (70%) of 20 limbs group II limbs compared with controls, which
      demonstrated an internal valgus stress. This internal varus moment was greater in
      group I limbs than in the abnormal limbs in group II (p < 0.05). Knee flexion was
      the only other parameter found to correlate with this stress and only in group I
      limbs. We conclude that (a) in this patient group, increased external tibial
      torsion is likely to result in an abnormal internal varus knee stress; (b) TFA >
      20 degrees appears significantly to increase this stress; and (c) knee flexion is
      an important related parameter, but only in limbs with TFA between 10 and 20
      degrees. We believe that this abnormal stress may predispose the knee to late
      arthrosis and that derotational osteotomies to normalize the TFA may prove to
      have a favorable long-term effect.

PMID- 9661846
TI  - Bilateral dislocation of the hip in spina bifida: a long-term follow-up study.
AB  - Nineteen patients with spina bifida and bilateral dislocation of the hips were
      studied with a minimal follow-up of 10 years. The average age at review was 21
      years (range, 10-31). Ten patients had an upper neurologic level (thoracic to
      L3), and nine had a low lesion (L4 to sacrum). Three patients had no hip surgery.
      A closed or open reduction was performed in 12 hips, supplemented by one or more
      surgical procedures. Of these, 10 remained enlocated, and two had redislocated.
      In all other hips, several surgical procedures were performed, aimed at
      improvement of hip-flexion deformity or stability. At follow-up, one patient had
      occasional pain in one hip, which was dysplastic. Of the 10 patients with a high
      lesion, only two were walkers, but both had bilateral dislocation of the hips at
      follow-up. In contrast, all nine patients were walkers, but four of these had
      bilateral dislocation at follow-up. We found that a level pelvis and good range
      of motion of the hips are more important for ambulation than is reduction of
      bilateral hip dislocation.

PMID- 9661847
TI  - Pseudo-Volkmann's contracture due to tethering of flexor digitorum profundus to
      fractures of the ulna in children.
AB  - We studied seven children with the unusual complication of pseudo-Volkmann's
      contracture due to tethering of the flexor digitorum profundus to fractures of
      the ulna. It was detected 2 days to 16 years after closed reductions of fractures
      of the shafts of the radius and ulna. The children did not have nerve palsies or
      undue pain after the reductions. Normal length, excursion, and function of the
      flexor digitorum profundus was restored by untethering the muscle and its tendons
      from the ulnar fracture by early manipulation or by late localized myotenolysis.
      We recommend that the passive range of motion of all fingers be routinely checked
      immediately after closed reductions of fractures of the radius and ulna. If
      muscle tethering is detected, the fracture is remanipulated to release the
      muscle. If the muscle is still tethered, then surgical release, through a small
      incision, is required.

PMID- 9661848
TI  - The effect of elbow position on the radial pulse measured by Doppler
      ultrasonography after surgical treatment of supracondylar elbow fractures in
      children.
AB  - We performed a prospective study of 20 patients with displaced extension
      supracondylar humerus fractures and evaluated the effect of elbow flexion,
      forearm supination, and forearm pronation on blood flow to the injured arm after
      closed reduction and Kirschner wire fixation. Ten patients had a Gartland type II
      fracture and 10 patients had a Gartland type III fracture. After closed reduction
      and percutaneous pinning, the radial pulse was examined with Doppler
      ultrasonography starting with the elbow in extension. The elbow was slowly
      flexed, and the angle of elbow flexion at which the radial pulse disappeared was
      determined. This angle of elbow flexion was measured with the forearm in both
      supination and pronation. Gartland type III fractures demonstrated less elbow
      flexion prior to radial pulse ablation compared to Gartland type II fractures
      when the forearm was placed in supination (p = 0.001) and in pronation (p =
      0.005). Supination allowed > or = 5 degrees of elbow flexion prior to radial
      pulse ablation in six Gartland type II and four Gartland type III fractures. We
      concluded that after closed reduction and percutaneous Kirschner wire fixation of
      displaced extension supracondylar fractures, vascular safety is enhanced by
      extending the elbow and supinating the forearm. The ideal position of elbow
      immobilization depends on the amount of swelling and the presence of a radial
      pulse.

PMID- 9661849
TI  - Cosmetic results of supracondylar osteotomy for correction of cubitus varus.
AB  - From 1984 to 1995, 19 patients with cubitus varus resulting from supracondylar
      humeral fractures underwent lateral closing-wedge osteotomies at The Royal
      Alexandra Hospital for Children. As the indication for osteotomy in all cases was
      the cosmetically unacceptable cubitus varus, we reviewed the cosmetic results.
      Seventeen patients were available for review. Subjective reports from patients
      and parents, as well as objective clinical assessment by one of the authors, were
      used to assess these results. According to our grading system, 12 (76%) patients
      had excellent results. These patients and their parents were satisfied with the
      cosmetic results, and there was no clinical evidence of a bony prominence over
      the lateral condylar region or an unsightly operative scar. One patient had a
      poor result with a lateral bony prominence and an unsightly scar, both of which
      were clinically obvious. We report that lateral closing osteotomies in children
      who have not yet reached skeletal maturity produce excellent cosmetic results.

PMID- 9661850
TI  - Nonoperative treatment for minimally and nondisplaced lateral humeral condyle
      fractures in children.
AB  - The radiographic and clinical records of 95 children with nondisplaced or
      minimally displaced fractures of the lateral humeral condyle treated on a
      nonoperative protocol were reviewed. Acute nondisplaced or minimally displaced
      fractures were defined as < 24 h old on initial evaluation and displaced < 2 mm
      in three radiographic planes (anteroposterior, lateral, and internal oblique).
      Closed treatment and close follow-up in a long-arm cast or splint resulted in a
      union rate of 98% in 3-7 weeks. Two of the fractures displaced required open
      reduction and internal fixation and then subsequently went on to union without
      complications.

PMID- 9661851
TI  - Intramedullary fixation of unstable both-bone forearm fractures in children.
AB  - A retrospective study was performed to evaluate the results of intramedullary
      fixation used in the management of unstable, diaphyseal both-bone forearm
      fractures in skeletally immature patients. Twenty-five patients with 25 fractures
      were identified whose fracture management included only intramedullary fixation.
      Galeazzi, Monteggia, radial head, and distal metaphyseal fractures were excluded
      from this analysis. Mean age at fracture was 10 + 8 years. There were 15 closed
      and 10 open fractures (eight grade I and two grade II). Smooth Kirschner wires or
      Rush rods were used for fixation. Average length of immobilization was 8 + 2
      weeks; 6 + 2 in a long-arm cast and 2 + 0 weeks in a short-arm cast. All 25
      regained normal elbow motion, with 17 regaining full forearm rotation. Eight
      patients had an average loss of 13 degrees of supination and 9 degrees of
      pronation. There were four minor and two major complications (one rod migration
      and one delayed union). No infections, malunions, or synostoses occurred in this
      patient group. Using the grading scheme adapted by Price there were 21 excellent
      results (84%), four good (16%), and no fair or poor results. In our experience,
      intramedullary fixation of the unstable both-bone forearm fractures is a safe,
      effective, and user-friendly technique when alignment jeopardizes fracture
      position at union and eventual forearm motion.

PMID- 9661852
TI  - Elastic intramedullary nailing: a minimally invasive concept in the treatment of
      unstable forearm fractures in children.
AB  - The standard treatment in forearm fractures in children is usually conservative.
      Unstable fractures of the proximal parts of the forearm often show poor results
      after nonoperative management so that these fractures usually require surgical
      intervention. We report 30 children (ages, 4-14 years) who were treated by
      elastic intramedullary nailing. Sixteen patients were treated by intramedullary
      splinting immediately after their accident; 14 children required intramedullary
      nailing after failure of conservative treatment and fracture redisplacement. At
      the time of follow-up 6 months later, functional results were excellent in 24
      children, good in five children, and fair in one child. There were no serious
      complications other than one delayed union. According to these results
      intramedullary nailing can be recommended for the treatment of unstable fractures
      of the proximal and middle thirds of the forearm in children.

PMID- 9661853
TI  - Carpal fractures in children.
AB  - Carpal fractures in children are uncommon injuries, with the scaphoid being
      fractured most frequently. Thirty-three children with scaphoid fractures and one
      child each with fractures of triquetrum, trapezoid, hamate, and capitate were
      retrospectively reviewed. The mean age was 13 years, 4 months. The mechanism of
      injury was of low energy in most cases, with > 80% of injuries involving a fall.
      Localizing tenderness was present in 100% of cases. Of fractures, 97.3% were
      evident on the initial radiographs. One patient required a bone scan to confirm
      the diagnosis. All but one scaphoid fracture went on to union with conservative
      treatment in a long-arm thumb spica cast or short-arm thumb spica cast at a mean
      of 7.1 weeks. All other carpal fractures healed at a mean of 4.5 weeks. The one
      scaphoid nonunion was attributed to noncompliance by the patient.

PMID- 9661854
TI  - Fracture of the cuboid in children: case report and review of the literature.
AB  - Although fractures of the cuboid are rare, they can be very disabling. The
      diagnosis is often missed, and overlooked cuboid fractures can lead to severe
      alterations in foot mechanics and function. We report the case of a displaced
      compression fracture of the cuboid in an 8-year-old girl after a fall from a
      height, which we treated by open reduction, bone grafting, and internal fixation.
      Follow-up examination 2 years after the injury revealed a very good result.
      Cuboid fractures should be considered in the differential diagnosis of limping
      toddlers. Children seen with pain, swelling, and inability to bear weight on the
      lateral aspect of the foot require proper evaluation and treatment.

PMID- 9661855
TI  - Calcaneal fractures in children.
AB  - Calcaneal fractures are rare in children but frequent in adults. We report 18
      cases (20 feet) of pediatric calcaneal fractures before the distal tibial growth
      line closed to assess the characteristics of pediatric calcaneal fractures and
      reveal differences in treatment and prognosis between children and adults. Twelve
      (60%) of the fractures were extraarticular, a higher percentage than in adults,
      and only four (20%) were intraarticular fractures associated with displacement.
      One case of avulsion fracture of the portion of the calcaneus where the Achilles
      tendon inserts, in which there was large displacement, and one intraarticular
      fracture were treated surgically. The outcome was good, including the surgical
      cases. One of the reasons that calcaneal fractures are considered rare in
      children is that they are missed, and thus care is required in making the
      diagnosis.

PMID- 9661856
TI  - Follow-up study of arthroscopic reduction and fixation of type III tibial
      eminence fractures.
AB  - Nine children (average age, 13.1 years) with 10 displaced type III tibial
      eminence fractures were reviewed with an average follow-up of 3.5 years. The
      fractures were treated with arthroscope-assisted reduction and suture fixation.
      Nine of the 10 knees demonstrated meniscal interposition at the fracture site
      that contributed to unsuccessful closed reduction. At follow-up, subjective knee
      function was excellent in all cases, and no clinical or objective evidence of
      knee laxity or instability was detected in any patient. All patients demonstrated
      full range of motion of the affected knee compared with the contralateral side.
      CLINICAL SIGNIFICANCE: Arthroscopic reduction and fixation allow early
      mobilization; assists in defining and treating associated knee pathology; assists
      in fracture reduction; and reduces the morbidity associated with arthrotomy.

PMID- 9661857
TI  - Home traction of femoral shaft fractures in younger children.
AB  - The study describes a home traction program of femoral shaft fractures in
      preschool children using the 90-90 traction technique. A special bed stretcher
      was designed for the program and adapted for use in ordinary ambulances and in
      all types of homes. Twenty-four patients, 2.2-5.9 years of age, were followed.
      The average hospital stay was 7.0 days, and the average home traction period was
      22.1 days. One patient had a superficial pin tract infection. The treatment was
      uneventful in all other cases. All fractures healed with a shortening of < or = 1
      cm. The angulation was < or = 10 degrees in all cases but one, which healed with
      a valgus angulation of 15 degrees but without functional disability. Interviews
      showed that the parents were very satisfied with the treatment program. The cost
      savings are obvious compared to traction treatment in the hospital.

PMID- 9661858
TI  - Femur fractures in children: treatment with early sitting spica casting.
AB  - The purpose of this article is to review our experience with early spica casting
      and determine risk factors for loss of reduction and skin complications. The
      radiographic and clinical charts of 114 children were retrospectively reviewed.
      At the time of fracture union, excessive shortening and angular malunion were not
      significant problems. Loss of reduction and skin complications occurred in 20 and
      14% of patients, respectively. In addition to previously described risk factors,
      we identified spica knee flexion angle < 50 degrees as predictive of eventual
      loss of reduction and found that > 2 cm of initial shortening was not a
      contraindication to early spica casting. Factors associated with skin problems
      included younger age and abuse as a mechanism of injury. In our opinion, early
      spica casting is the treatment of choice for all isolated, closed femur fractures
      in otherwise healthy children aged 6 years or younger, regardless of the degree
      of initial deformity.

PMID- 9661859
TI  - Evaluating blood loss in children's orthopaedic surgery: a simplified method of
      photometric analysis of eluted swabs.
AB  - Assessment of intraoperative blood loss by the traditional method of weighing
      swabs (4 x 4-in. gauze) is propounded to estimate approximately 75% of total
      loss, although many believe this still underestimates actual loss. The various
      components of this technique were studied by using the method of colorimetric
      analysis of eluted swabs, but utilising a modern spectrophotometer. We modified
      and simplified the technique, resulting in > 95% accuracy in all instances, and
      by so doing, created a potential technique for use in children's orthopaedic
      surgery. Weighing swabs was found to estimate only approximately 50% of total
      loss, and this was supported in the pilot clinical study by a postoperative
      decrease in haemoglobin of 8-17%, despite transfusion, when transfusion was based
      on the traditional "75%" rule. Because it is impractical to elute theatre apparel
      and instruments to increase the accuracy of the elution method in the
      perioperative time scale necessary, a compromise may be to use the new "50%" rule
      as a better estimate of total blood loss when calculating transfusion
      requirements.

PMID- 9661860
TI  - Epidural analgesia for postoperative pain control in children.
AB  - Ninety-eight continuous postoperative epidurals were administered to 87 children.
      The patients were divided into two groups: group I included 63 cases in which a
      0.0625-0.25% solution of bupivacaine was continuously administered; group II
      included 35 cases in which a similar solution of bupivacaine mixed with 2-10
      micrograms of fentanyl was administered. The dose of the epidural medication was
      titrated by the anesthesiologist according to the patient's age and anticipated
      level of postoperative pain. The average pain score for all patients for the
      first 48 h was 1.43. Supplemental analgesia averaging 0.132 mg intravenous
      morphine/kg/8 h was required in 49 cases (41 in group I and eight in group II).
      In group I, the average dose of supplemental analgesia was 0.144 mg intravenous
      morphine/kg/8 h, whereas in group II, it was only 0.056 mg intravenous
      morphine/kg/8 h. Continuous epidural analgesia is effective in controlling
      postoperative pain, and the addition of fentanyl reduces the need for systemic
      narcotics.

PMID- 9661861
TI  - Normal postoperative febrile response in the pediatric orthopaedic population.
AB  - Postoperative fever in the pediatric orthopaedic population remains a clinical
      concern even though prior studies concluded that fevers are a poor predictor of
      surgical complications. In this retrospective study of 177 patients, we
      established guidelines regarding the degree and time course of fever we should
      expect based on the perioperative conditions of magnitude of surgery, duration of
      surgery, need for intraoperative transfusion, estimated blood loss, age, and
      gender. To provide a more sensitive assessment of fever, we developed composite
      temperature curves for each patient and defined the area under these curves as
      the total febrile response (TFR). This allowed us to assess fever as a cumulative
      event, taking into account both its magnitude and duration. A multivariate model
      then determined that of the perioperative conditions studied, intraoperative
      transfusion status and estimated blood loss were most helpful in predicting a
      patient's TFR. The results of this study can be used as an additional tool for
      assessing postoperative progress and whether a fever is within the normal limits
      indicated by a patient's perioperative variables.

PMID- 9661862
TI  - Comparison of crossed pins and external fixation for correction of angular
      deformities about the knee in children.
AB  - External fixation was compared to crossed Steinman pins and plaster for fixation
      after osteotomy about the knee in children. A group of 26 patients treated by
      external fixation was compared to a control group of 26 patients fixed with
      crossed Steinman pins and casting. The groups were matched for age, height, and
      weight. Overall there was a 100% union rate. Preoperative deformity and
      postoperative correction were similar in the two groups. The time to union was
      significantly longer, and there were significantly more complications in the
      external fixator group. There were 16 complications (62%) in the external fixator
      group and five (19%) in the control group. Complications included pin tract
      infections, peroneal nerve palsy, and delayed union. External fixation provides
      certain advantages for fixation after osteotomies about the knee in children but
      is associated with a variety of complications.

PMID- 9661863
TI  - Instability of the patellofemoral joint in Rubinstein-Taybi syndrome.
AB  - Twenty-five (3.4%) of 732 individuals with Rubinstein-Taybi syndrome were noted
      to have instability of the patellofemoral joint. We believe that this is in fact
      an underrepresentation of the true incidence, as we were able to identify only
      those patients whose symptoms were most severe. These individuals typically had
      symptoms before or during their adolescent growth spurt, had bilateral
      involvement, and in some instances, ceased to ambulate because of their
      patellofemoral problems. A subset of these individuals underwent patellar
      realignment surgery, with those whose treatment did not include extensive
      quadriceps mobilization/quadricepsplasty having a 2.7 times higher risk of
      requiring revision patellar surgery. Patellofemoral instability associated with
      Rubinstein-Taybi syndrome demands early recognition and treatment to prevent
      potentially catastrophic gait disturbances.

PMID- 9661864
TI  - Correction of proximal tibial deformities in adolescents with the T-Garches
      external fixator.
AB  - Frontal-plane deformity of the proximal tibia in children has a variety of
      etiologies. There are also a number of described surgical techniques for
      correction of these deformities. The authors reviewed their early experience with
      the use of the Orthofix T-Garches external fixator for correction of 16 proximal
      tibial deformities in 14 patients. Mean age at surgery was 14.2 years. The most
      common diagnosis was adolescent Blount's disease. Average deformity was 12
      degrees. Total treatment time averaged 13 weeks for those requiring lengthening
      and 10.8 weeks for those without. Complications included one ring sequestrum
      treated by curettage, and two patients with subsequent development of femoral
      deformity. Tibial anatomic axis averaged 1 degree of varus. This device can
      achieve excellent correction of deformity isolated to the frontal plane with few
      complications. It allows functional weight bearing and use of adjacent joints
      during treatment.

PMID- 9661865
TI  - Posttraumatic genu valgum: operative versus nonoperative treatment.
AB  - The purpose of this study was to compare the results of operative versus
      nonoperative treatment for posttraumatic genu valgum. It is a retrospective chart
      and radiograph review of all patients with the diagnosis of posttraumatic genu
      valgum from our institution and from data obtained in response to 389 letters
      sent to the members of the Pediatric Orthopaedic Society of North America
      (POSNA). The complementary physeal shaft (CPS) angle and the tibial femoral angle
      (TFA) were measured at the time of injury, at maximal deformity, and at latest
      follow-up. Fifteen patients were identified, 10 in the nonoperative group and
      five in the operative group. In both groups, the valgus deformity progressed over
      a 20-month span. In both groups, the valgus deformity improved at the time of
      follow-up. There was no significant difference in the CPS angle or TFA, between
      groups at the time of injury, at maximal deformity, or at follow-up.

PMID- 9661866
TI  - Modified adductor muscle transfer in cerebral palsy.
AB  - Eighty-five patients with cerebral palsy had modified adductor muscle transfers.
      A study of associated patient characteristics suggests that comparing adductor
      transfer with adductor release using postoperative radiographs, need for
      subsequent surgery, or postoperative motor skills is flawed by multiple
      variables. Adductor release and adductor transfer are best compared by measuring
      the abduction obtained at surgery and maintained over time. A follow-up of 141
      modified adductor transfers with no prior or concomitant hip surgery demonstrated
      an averaged initial improvement in abduction of 43 degrees and maintenance of
      abduction with a low incidence of recurrence.

PMID- 9661867
TI  - Pathologic morphology of the dislocated proximal femur in children with cerebral
      palsy.
AB  - We describe the gross and microscopic anatomic changes in the hip that result
      from the deforming forces in children with neuromuscular imbalance. Twelve
      dislocated proximal femora that had been resected from children with spastic
      diplegia or tetraplegia were evaluated with respect to their gross, microscopic,
      and radiographic structure. The epiphyses were wedge shaped with deformation of
      the femoral head apparent in all cases. In addition to a severe loss of articular
      cartilage, a furrowed erosion of epiphyseal bone suggested a sustained, blunt,
      band-like force across the surface of the hip where it opposed the acetabular
      labrum. The underlying physis of the capital femur was irregular with aberrant
      histologic structure, whereas that of the lesser trochanter was hypertrophic and
      angulated in a superior and anterior direction. A significant degree of valgus
      was not noticeable in most specimens. In summary, the spastic adductor and
      iliopsoas, responsible for the changes in the lesser trochanter, work in
      conjunction with the hip flexor and internal rotator muscles to subluxate the
      proximal femur. In the process, the superior rim of the acetabulum and capsule
      causes focal deformation of the superolateral femoral head, creating a fulcrum
      upon which the hip then progressively subluxates. The indentation locks the
      femoral head at the lateral acetabular margin, preventing complete dislocation,
      but leading to bone pain consequent to cartilage erosion.

PMID- 9661868
TI  - Serum relaxin in the newborn is not a marker of neonatal hip instability.
AB  - It has been suggested that intrauterine exposure to high levels of relaxin causes
      hip instability in newborns. The aim of this work was to evaluate whether the
      serum relaxin concentration in umbilical vein blood is associated with hip
      instability in the newborn. Blood was collected by cordocentesis from 2,185
      newborns, and serum relaxin levels were obtained by using a standard sandwich
      enzyme-linked immunosorbent assay (ELISA). Movement of the femoral head in the
      hip joint was determined for all 2,185 children by the anterior-dynamic
      ultrasound method. Hereby their status on neonatal hip instability was
      determined. Fifteen cases (12 girls, three boys) were found, and 106 controls
      were selected. Only six newborns had unstable hips to a degree requiring
      treatment. Ten newborns had Ortolani-positive hips. Only three specimens of the
      121 samples measured had serum relaxin concentrations above the detection limit
      of 10 pg/ml. None of these were cases. This study does not show an association of
      serum relaxin with neonatal hip instability. It is suggested that detectable
      serum relaxin levels are found in samples from the umbilical cord only when these
      are contaminated with maternal blood.

PMID- 9661869
TI  - Nonsurgical treatment of congenital clubfoot with manipulation, cast, and
      modified Denis Browne splint.
AB  - Between 1974 and 1988, 113 congenital clubfeet in 76 children were consecutively
      treated by using a modified Denis Browne splint with an aluminum crossbar between
      a pair of plastic shoe inserts after a few manipulations and a corrective cast.
      Splintage was followed by surgery in 41 (36%) feet. Sixty-nine feet that did not
      undergo surgery were evaluated after an average follow-up period of 12 years.
      Sixty-six (95%) feet were excellent or good, according to the McKay rating
      system. The success rate of this treatment was 60% when the 41 feet receiving
      surgery and the three feet with fair or poor outcome were evaluated as failures.
      The success rate was 42% in severely deformed feet, 70% in moderately deformed
      feet, and 100% in mildly deformed feet. This treatment was effective for
      congenital clubfoot with mild or moderate deformity and was sometimes effective
      for severe deformity.

PMID- 9661870
TI  - Dysplasia epiphysealis hemimelica: clinical features and management.
AB  - Dysplasia epiphysealis hemimelica is a rare developmental bone dysplasia
      characterized by an osteocartilaginous tumor arising from an epiphysis. We
      reviewed the clinical and radiographic findings, including magnetic resonance
      imaging (MRI), of nine new patients with dysplasia epiphysealis hemimelica. The
      lower limb was involved in all cases with the ankle (talus) and knee (distal
      femur) being the most common sites. MRI was helpful in defining the site and
      extent of the osteocartilaginous mass and provided detailed images of associated
      joint deformity. Often there was a clear plane of separation between the lesion
      and the normal epiphysis. All cases were observed initially and showed
      progressive increase in size of the lesion with skeletal growth. Surgical
      excision was performed in five cases and proved to be difficult. We recommend
      excision of symptomatic localized, juxtaarticular lesions but do not recommend
      excision of articular lesions. Postoperative degenerative joint changes occurred
      in two patients.

PMID- 9661871
TI  - Is a routine radiological consultation cost-effective for pediatric orthopedic
      radiographs?
AB  - This investigation was undertaken to determine the value of a routine
      radiological consultation on all examinations taken during the course of
      evaluation and treatment of children with elective orthopedic problems. Shriners
      Hospital in Los Angeles treats children with chronic orthopedic problems. All
      radiographs are ordered by an orthopedic surgeon. Currently all plain
      examinations are also read and reported by a pediatric radiologist. The study was
      a retrospective chart review. Three hundred nineteen radiographic examinations
      (6.7% of the total performed in calendar year 1995) were reviewed. The orthopedic
      surgeons documented the results of their readings in 69% of the cases, while the
      radiology staff documented 92% of the studies. The data do not show evidence of
      significant misinterpretations in the readings by the orthopedic surgeons.
      Therefore routine radiological consultation for all examinations is unnecessary
      in that specific setting. If a policy change were instituted, it would represent
      a major saving in health-care costs.

PMID- 9661872
TI  - Ultrasonography: can it differentiate between vasoocclusive crisis and acute
      osteomyelitis in sickle cell disease?
AB  - We prospectively evaluated the results of ultrasonography in 53 patients of
      sickle cell disease suspected to have vasoocclusive crisis/acute hematogenous
      osteomyelitis. The average age was 8.4 +/- 3.40 years (range, 1-14). Twenty-six
      children were boys and 27 were girls. Seventeen (32%) patients had
      ultrasonographic changes that suggested acute osteomyelitis. The minimal white
      cell count was 7,200/mm3, and maximal, 9,900/mm3 (mean, 8,190/mm3) in uninfected
      patients and in 17 patients, the mean was 10,300/mm3 (7,200-13,600/mm3). The mean
      erythrocyte sedimentation rate in uninfected patients was 32 for the first hour
      (19-36 mm), and in infected patients, it was 43 for the first hour (35-38 mm).
      Pus culture was positive in all infected patients, and the infective organism was
      Salmonella enteriditis in eight, staphylococcal species in six (S. aureus in four
      and S. epidermidis in two), and Streptococcus species 1 and 2, anaerobic
      streptococci. All patients with vasoocclusive crisis were treated with analgesics
      and intravenous fluids and did not require any further treatment. In patients
      with acute osteomyelitis, the treatment was incision, drainage and drilling of
      bone, and antibiotic therapy. We conclude that ultrasonography clearly and
      decisively differentiated acute osteomyelitis from vasoocclusive crisis in
      patients with sickle cell disease.

PMID- 9661873
TI  - For the child with spastic hip subluxation the indication for surgery is pain.

PMID- 9661874
TI  - Enhancement of oxidative cell injury and antitumor effects of localized 44
      degrees C hyperthermia upon combination with respiratory hyperoxia and xanthine
      oxidase.
AB  - The effects of respiratory hyperoxia (RH) and xanthine oxidase (XO) during
      localized hyperthermia (HT) were investigated by determining markers of oxidative
      damage to lipids and proteins and tumor growth. Anesthetized rats with s.c. DS
      sarcomas underwent one of the following treatments: (a) localized saline-bath HT
      (60 min, 44 degrees C); (b) HT + RH (100% O2); and (c) HT + RH + XO (15 units/kg
      i.v.). Sham-treated animals served as controls. Tumors were investigated for: (a)
      thiobarbituric acid-reactive substance formation and protein-bound 4
      hydroxynonenal, as indicators of lipid peroxidation; (b) reactive oxygen-mediated
      protein modifications; (c) apoptosis; and (d) tumor volume growth. Upon
      treatment, increases in thiobarbituric acid-reactive substances, protein-bound 4
      hydroxynonenal, protein-associated carbonyl functions, and number of cells
      undergoing apoptosis were found in tumor tissue, together with an inhibition of
      tumor growth. When treatment groups were compared, effects in the group HT + RH +
      XO were generally most pronounced. These findings indicate that the antitumor
      effect of HT is at least partially mediated through the selective induction of
      lipid peroxidation and oxidative injury in tumor cells, leading to apoptosis.
      This effect was enhanced by adding RH or RH + XO, presumably due to enhanced
      tissue damage following an increased formation of reactive oxygen species, with
      higher levels of lipid peroxidation and protein oxidation.

PMID- 9661875
TI  - Perturbation of TSG101 protein affects cell cycle progression.
AB  - tsg101 was recently identified as a tumor susceptibility gene by functional
      inactivation of allelic loci in mouse 3T3 fibroblasts. Although previous studies
      suggested that homozygous intragenic deletion of TSG101 is rare in breast cancer
      cells and specimens, the neoplastic phenotype caused by tsg101 inactivation
      implicated that tsg101 may play a significant role in cell growth control. Here,
      we characterize mouse polyclonal and monoclonal antibodies that specifically
      recognize the TSG101 protein (molecular mass, 46 kDa) in whole-cell lysates by
      straight Western blot analysis. By indirect immunofluorescence staining, TSG101
      was found to be localized in the cytoplasm throughout the entire cell cycle.
      However, the nuclear staining increases from G1 to S phase and becomes dominant
      in late S phase. TSG101 is mainly distributed surrounding the chromosomes during
      M phase. The expression level of TSG101 is not cell cycle dependent. It is
      possible that the relocalization of TSG101 from the cytoplasm into the nucleus
      may be relevant to its function. Microinjection of both polyclonal and monoclonal
      antibodies specific to TSG101 into cells during G1 or S phase results in cell
      cycle arrest. Furthermore, overexpression of TSG101 leads to cell death,
      suggesting that the appropriate amount of TSG101 is critical for cell cycle
      progression. Taken together, these results suggest that neoplastic transformation
      caused by TSG101 deficiency may result from bypassing of the cell cycle
      checkpoints.

PMID- 9661876
TI  - Interleukin 1beta-converting enzyme (caspase-1) is overexpressed in
      adenocarcinoma of the pancreas.
AB  - We investigated the expression of interleukin 1beta-converting enzyme (ICE;
      caspase-1) in human adenocarcinomas of the pancreas. Immunohistochemistry and
      Western blot analyses revealed an overexpression of ICE in 71 and 80% of tumor
      cells, respectively. Also, on a mRNA level, ICE mRNA was overexpressed in 45% of
      the cases, as compared to normal pancreatic tissue. Interestingly, the
      overexpression of ICE in tumor cells correlated significantly with the
      overexpression of cyclin D1, epidermal growth factor, and epidermal growth factor
      receptor (P < 0.0005, P < 0.05, and P < 0.002, respectively), which are involved
      in cell cycle progression and proliferation in human pancreatic carcinoma. This
      is the first report concerning ICE expression in human carcinomas; however, the
      exact mechanism underlying these close correlations warrant further research.

PMID- 9661877
TI  - Vaccination with tumor cells engineered to secrete interleukin 2-immunoglobulin G
      fusion protein induces tumor rejection.
AB  - Here we provide proof that the injection of tumor cells engineered to secrete
      interleukin 2 (IL-2)-IgG chimeric proteins locally induces potent antitumor
      responses, which are more effective than tumor transfection with IL-2 alone.
      Murine plasmacytoma cells (J558L) were stably transfected with DNA coding for a
      human IL-2-IgG1 or a murine IL-2-IgG2b fusion protein and were injected s.c. into
      syngeneic BALB/c mice. Evaluation of tumor growth and rejection patterns showed
      that IL-2-IgG secretion by transfected J558L tumor cells induced their rejection
      in all animals tested, similar to the rejection of J558L cells engineered to
      secrete IL-2 alone, whereas treatment with parental cells was lethal. However,
      mice treated with IL-2-IgG-secreting J558L cells (human IL-2-IgG1 and murine IL-2
      IgG2b) exhibited a significantly stronger tumor immunity against a later
      challenge with parental J558L cells than mice treated with IL-2-secreting tumor
      cells.

PMID- 9661878
TI  - Unsymmetrically substituted polyamine analogue induces caspase-independent
      programmed cell death in Bcl-2-overexpressing cells.
AB  - The polyamine analogue, N1-ethyl-N11-[(cycloheptyl)methyl]-4,8-diazaundecane
      (CHENSpm)-induced programmed cell death in NCI H157 cells is accompanied by
      cytochrome c release, the loss of mitochondrial membrane potential, activation of
      caspase-3, caspase-mediated poly(ADP-ribose) polymerase cleavage, G2-M arrest,
      and DNA and nuclear fragmentation. Overexpression of Bcl-2 completely inhibits
      CHENSpm-induced cytochrome c release, caspase-3 activation, and poly(ADP-ribose)
      polymerase cleavage. However, Bcl-2 does not abrogate CHENSpm-induced programmed
      cell death. These results suggest that although cytochrome c release and
      activation of the caspase-3 protease cascade contribute to the rapid and
      efficient execution of apoptosis, a caspase cascade-independent pathway also
      exists and can be activated by CHENSpm treatment.

PMID- 9661879
TI  - Genetic changes in inherited and sporadic ovarian carcinomas by comparative
      genomic hybridization: extensive similarity except for a difference at chromosome
      2q24-q32.
AB  - Germ-line mutations in the BRCA1 and BRCA2 genes confer a predisposition to
      breast as well as ovarian carcinoma. Except for loss of the respective wild-type
      allele, somatic genetic changes needed for the progression of inherited ovarian
      tumors are unknown. A genome-wide search for such alterations was performed by
      comparative genomic hybridization analysis on BRCA1 and BRCA2 mutation-positive
      (n = 20) ovarian carcinoma specimens. Comparison with sporadic ovarian carcinomas
      (n = 20) revealed extensive genetic similarity between the inherited and sporadic
      carcinomas with the sole exception of a frequent gain of 2q24-q32 in the
      inherited group, suggesting the presence of an oncogene at 2q24-q32 operating in
      the absence of BRCA1 function. The overall similarity of gains and losses by
      comparative genomic hybridization suggests a common main pathway in tumor
      progression of both inherited and sporadic ovarian carcinomas.

PMID- 9661880
TI  - Frequent inactivation of PTEN in prostate cancer cell lines and xenografts.
AB  - Loss of chromosome 10q is a frequently observed genetic defect in prostate
      cancer. Recently, the PTEN/MMAC1 tumor suppressor gene was identified and mapped
      to chromosome 10q23.3. We studied PTEN structure and expression in 4 in vitro
      cell lines and 11 in vivo xenografts derived from six primary and nine metastatic
      human prostate cancers. DNA samples were allelotyped for eight polymorphic
      markers within and surrounding the PTEN gene. Additionally, the nine PTEN exons
      were tested for deletions. In five samples (PC3, PC133, PCEW, PC295, and PC324),
      homozygous deletions of the PTEN gene or parts of the gene were detected. PC295
      contained a small homozygous deletion encompassing PTEN exon 5. In two DNAs (PC82
      and PC346), nonsense mutations were found, and in two (LNCaP and PC374), frame
      shift mutations were found. Missense mutations were not detected. PTEN mRNA
      expression was clearly observed in all cell lines and xenografts without large
      homozygous deletions, showing that PTEN down-regulation is not an important
      mechanism of PTEN inactivation. The high frequency (60%) of PTEN mutations and
      deletions indicates a significant role of this tumor suppressor gene in the
      pathogenesis of prostate cancer.

PMID- 9661881
TI  - Absence of PTEN/MMAC1 germ-line mutations in sporadic Bannayan-Riley-Ruvalcaba
      syndrome.
AB  - Bannayan-Riley-Ruvalcaba syndrome (BRRS) is a rare hamartomatous polyposis
      condition with features of macrocephaly, intestinal juvenile polyposis,
      developmental delay, lipomas, and pigmentation spots of the male genitalia. An
      autosomal dominant pattern of inheritance exists in some families, but others
      appear as sporadic cases. Germ-line mutations in PTEN, a tyrosine phosphatase and
      putative tumor suppressor gene, have been demonstrated in two families with BRRS,
      and chromatin loss at the PTEN gene locus on chromosome 10q23 has been
      demonstrated in two BRRS patients. Germ-line mutations in PTEN have also been
      described in Cowden disease and in a small number of patients with juvenile
      polyposis syndrome. In an attempt to assess the nature of PTEN mutations in BRRS,
      we analyzed three sporadic BRRS patients for chromosome 10q23 deletion or PTEN
      germ-line mutations. All 3 patients demonstrated no loss of parental alleles at
      15 chromosome 10q23 markers that encompassed the region of PTEN. In addition,
      analysis of mRNA and genomic DNA revealed no nonsense, missense, or
      insertion/deletion mutations of PTEN. Thus, other mechanisms besides mutation of
      PTEN must have occurred to cause BRRS in these patients. We speculate that BRRS
      and juvenile polyposis syndrome may have a heterogeneous etiology to cause their
      syndromes.

PMID- 9661882
TI  - Type I transforming growth factor beta receptor maps to 9q22 and exhibits a
      polymorphism and a rare variant within a polyalanine tract.
AB  - In a search for mutations of the type I transforming growth factor beta receptor
      (TbetaR-I), we mapped the gene to 9q22 and found a common polymorphism [TbetaR
      I(6A)] and a rare variant [TbetaR-I(10A)] of TbetaR-I, causing an in-frame
      deletion of three alanines and an in-frame insertion of one alanine,
      respectively, in the receptor's extracellular domain. The biological relevance of
      the polymorphism TbetaR-I(6A) was investigated. When TbetaR-I(6A) was transiently
      transfected into TbetaR-I-deficient cells, the growth-inhibitory effects of
      transforming growth factor beta were restored. TbetaR-I(6A) and TbetaR-I(10A)
      frequency were assessed in 108 tumor samples and 80 nontumor samples from
      patients with a diagnosis of cancer, as well as in 118 normal blood donors of
      comparable ethnic composition. The frequency of TbetaR-I(6A) heterozygotes was
      fairly similar in normal blood donors (8%), in nontumor DNA of patients with a
      diagnosis of cancer (10%), and in tumor samples (14%). However, the frequency of
      TbetaR-I(6A) homozygotes among nontumor (4%) and tumor (8%) samples obtained from
      patients with a diagnosis of cancer was higher than that predicted by the Hardy
      Weinberg law. The clinical and biological significance of TbetaR-I(6A)
      homozygosity needs to be further investigated.

PMID- 9661883
TI  - Procathepsin-L, a proteinase that cleaves human C3 (the third component of
      complement), confers high tumorigenic and metastatic properties to human melanoma
      cells.
AB  - We previously demonstrated that highly metastatic human melanoma cells secrete a
      41 kDa proteinase that cleaves C3, the third component of complement, and shares
      antigenic determinants with procathepsin-L. Thus, we herein transfected the
      nonmetastatic DX-3 melanoma cells with the procathepsin-L cDNA. Three clones
      expressing and secreting high levels of procathepsin-L were selected. Conditioned
      medium and whole cell extracts from these clones, but not from control cells,
      carried a high C3-cleaving activity. The transfected clones displayed up to 60%
      resistance to complement-mediated lysis. Overexpression of procathepsin-L in
      melanoma cells increased their tumorigenicity and switched their phenotype from
      nonmetastatic to highly metastatic cells. This is the first report that
      demonstrates that enforced expression of procathepsin-L by human melanoma cells
      arms them with the ability to inactivate complement-mediated lysis and
      contributes to tumor growth and metastasis.

PMID- 9661884
TI  - Thymidine phosphorylase moderates thymidine-dependent rescue after exposure to
      the thymidylate synthase inhibitor ZD1694 (Tomudex) in vitro.
AB  - The inhibition of de novo thymidine (dThd) synthesis by the novel folate-based
      thymidylate synthase (TS) inhibitor ZD1694 (Tomudex) can achieve tumor cell
      specific cytotoxicity in vivo. However, nucleosides in the surrounding
      microenvironment of tumors may be used by the salvage pathway to regenerate any
      depleted pools, thus providing an efficient mechanism through which to circumvent
      the ZD1694-dependent toxicity. Anabolism of dThd to dTMP by dThd kinase (TK) is
      the first committed step in the dThd salvage pathway. However, dThd phosphorylase
      (dThdPase) can compete with TK by catalyzing the reversible phosphorolytic
      cleavage of dThd to thymine and deoxyribose 1-phosphate and rendering the
      salvaged dThd metabolically unavailable. Both TK and dThdPase are up-regulated in
      some tumors, and their relative importance is not fully defined. We have studied
      the influence of dThdPase expression on the capacity of exogenous dThd to reverse
      ZD1694-dependent growth inhibition and have shown that both intra- and
      extracellular dThdPase activity can effectively moderate dThd-rescue. This
      suggests that tumor levels of dThdPase may be an important factor in the outcome
      of ZD1694 therapy.

PMID- 9661885
TI  - Isolation of MOAT-B, a widely expressed multidrug resistance-associated
      protein/canalicular multispecific organic anion transporter-related transporter.
AB  - Multidrug resistance-associated protein (MRP) and canalicular multispecific
      organic anion transporter (cMOAT) are closely related mammalian ATP-binding
      cassette transporters that export organic anions from cells. Transfection studies
      have established that MRP confers resistance to natural product cytotoxic agents,
      and recent evidence suggests the possibility that cMOAT may contribute to
      cytotoxic drug resistance as well. Based upon the potential importance of these
      transporters in clinical drug resistance and their important physiological roles
      in the export of the amphiphilic products of phase I and phase II metabolism, we
      sought to identify other MRP-related transporters. Using a degenerate PCR
      approach, we isolated a cDNA that encodes a novel ATP-binding cassette
      transporter, which we designated MOAT-B. The MOAT-B gene was mapped using
      fluorescence in situ hybridization to chromosome band 13q32. Comparison of the
      MOAT-B predicted protein with other transporters revealed that it is most closely
      related to MRP, cMOAT, and the yeast organic anion transporter YCF1. Although
      MOAT-B is closely related to these transporters, it is distinguished by the
      absence of a approximately 200 amino acid NH2-terminal hydrophobic extension that
      is present in MRP and cMOAT and which is predicted to encode several
      transmembrane spanning segments. In addition, the MOAT-B tissue distribution is
      distinct from MRP and cMOAT. In contrast to MRP, which is widely expressed in
      tissues, including liver, and cMOAT, the expression of which is largely
      restricted to liver, the MOAT-B transcript is widely expressed, with particularly
      high levels in prostate, but is barely detectable in liver. These data indicate
      that MOAT-B is a ubiquitously expressed transporter that is closely related to
      MRP and cMOAT and raise the possibility that it may be an organic anion pump
      relevant to cellular detoxification.

PMID- 9661886
TI  - Ornithine decarboxylase induction in transformation by H-Ras and RhoA.
AB  - The objective of these studies has been to develop a better understanding of the
      regulation of ornithine decarboxylase (ODC) during the neoplastic process, and to
      determine whether induction of ODC is a necessary component in the action of the
      ras oncogene. Specifically, we have studied the role of ODC overexpression in
      signaling pathways mediated by Raf or RhoA. Cells transformed by ras are known to
      have constitutively high levels of ODC activity that correlate with oncogenic
      transformation. To determine which pathways downstream of Ras contribute to the
      regulation of ODC activity, NIH-3T3 cells were transfected with plasmids coding
      for activated mutants of either H-Ras or RhoA, or oncogenic nu-Raf. There was a
      good correlation between increasing ODC specific activity and change in
      morphology from normal to transformed in the nu-Raf, HRas(61L), and RhoA(63L)
      clones. Increasing ODC activity also correlated positively with the ability to
      grow in soft agar in both the H-Ras- and RhoA-expressing cells. In stable
      transfections, coexpression of the ODC dominant negative mutant K69A/C360A with
      either HRas(61L) or RhoA(63L) both inhibited intracellular ODC activity and
      caused a reversion of the transformed phenotype, as measured by a dramatic
      reduction in the ability of these cells to grow in soft agar and form foci on a
      monolayer. These results suggest strongly that ODC induction is necessary for
      transformation by oncogenic Ras. In contrast, expression of K69A/ C360A had no
      effect on the ability of nu-Raf-transformed cells to grow in soft agar, although
      intracellular ODC levels were inhibited. When grown on a monolayer, these cells
      also maintained their transformed appearance. Furthermore, expression of the ODC
      dominant negative mutant did not affect the phosphorylation of mitogen-activated
      protein kinase in nu-Raf-transformed cells. These experiments provide strong
      support for the concept that transformation by activated ras is accompanied by an
      induction of ODC. The results using RhoA(63L) and nu-Raf suggest that this
      increase in ODC activity is mediated at least in part through a Raf/ mitogen
      activated protein kinase independent pathway.

PMID- 9661887
TI  - Diosmin and diosmetin are agonists of the aryl hydrocarbon receptor that
      differentially affect cytochrome P450 1A1 activity.
AB  - We investigated the effect of the chemopreventive compound diosmin and its
      aglycone form, diosmetin, on the carcinogen activation pathway mediated by the
      aryl hydrocarbon receptor (AhR) in MCF-7 human breast epithelial cancer cells.
      Treatment of the cells with diosmin caused a dose-dependent increase in the
      metabolism of the mammary carcinogen 7,12-dimethylbenz(a)anthracene (DMBA), as
      assessed by increased formation of DMBA-DNA adducts and by DMBA-induced
      cytotoxicity. In contrast, treatment of the cells with diosmetin decreased both
      parameters. Diosmetin, but not diosmin, directly inhibited cytochrome P450 1A1
      (CYP1A1) activity in a noncompetitive manner in microsomes isolated from DMBA
      treated cells, as assayed by ethyoxyresorufin-O-deethylase activity. Treatment of
      the cells with diosmin or diosmetin, on the other hand, caused a dose- and time
      dependent increase in CYP1A1 activity in intact cells that was comparable to that
      induced by DMBA or by the aryl hydrocarbon benzo(a)pyrene. Both diosmin and
      diosmetin caused an increase in the transcription of the CYP1A1 gene, as measured
      by increased levels of CYP1A1 mRNA. Both compounds caused the activation of the
      DNA-binding capacity of the AhR for the xenobiotic-responsive element of CYP1A1.
      These results indicate that diosmin and diosmetin are natural dietary agonists of
      the AhR, causing a potent increase in CYP1A1 transcription and CYP1A1 activity;
      however, only diosmetin is capable of inhibiting CYP1A1 enzyme activity, thus
      inhibiting carcinogen activation.

PMID- 9661888
TI  - Detection and quantitation of circulating cancer cells in the peripheral blood of
      lung cancer patients.
AB  - Detection and quantitation of circulating cancer cells in peripheral blood may
      improve cancer staging and monitoring. This study explored the feasibility of
      using circulating cancer cell detection in peripheral blood for the rapid
      assessment of chemotherapeutic response. Cytokeratin 19 mRNA was amplified by
      nested reverse transcriptase-PCR in the peripheral blood of 29 healthy
      volunteers, 33 pneumonia patients, and 86 lung cancer patients. Circulating
      cancer cells in the peripheral blood were semiquantitatively determined by taking
      the ratio of cytokeratin 19 band intensity from the second round of nested PCR to
      the glyceraldehyde-3-phosphate dehydrogenase band intensity from the first round
      of PCR amplification. The detection limit of the method was 1 cancer cell in 107
      peripheral blood mononuclear cells. The positive detection rate was 40% for lung
      adenocarcinoma patients of all stages, 41% for squamous carcinoma patients of all
      stages, and 27% for small cell lung cancer patients. Only one control sample from
      a pneumonia patient showed a positive result (1.6%). The quantitative method
      reliably and sensitively estimated cancer cell numbers in the peripheral blood of
      lung cancer patients. Serial measurement of the relative number of circulating
      cancer cells correlated with the tumor burden and treatment response of patients.
      This method may help rapidly assess the efficacy of anticancer treatment,
      redefine cancer staging, and facilitate the design of better therapeutic
      strategies for the treatment of cancer patients.

PMID- 9661889
TI  - The relationship between nm23, angiogenesis, and the metastatic proclivity of
      node-negative breast cancer.
AB  - Distant metastases are the major cause of morbidity and mortality in women with
      breast cancer. The prediction of this metastatic proclivity is essential in
      determining prognosis and should allow an appropriate choice of therapy. A
      critical look at the metastatic process and its phenotypic expression offers an
      opportunity to identify some of the important events in the process that may
      relate to prognosis, with the goal of identifying those patients with occult
      metastases and also sparing systemic treatment in those patients whose tumors
      have not developed the capacity for distant spread. To evaluate the significance
      of nm23 and angiogenesis in the metastatic cascade, we used archival material
      from 163 node-negative breast cancer patients who had a median follow-up of 14
      years. All patients underwent mastectomy and received no adjuvant chemotherapy or
      hormone or radiation therapy. Immunohistochemistry was used to detect nm23-H1
      expression, whereas angiogenesis was determined by microvessel count (MVC). We
      found the 15-year disease-free survival (DFS) to be significantly better in
      patients with high nm23 compared with low nm23 (91% compared with 70%, P =
      0.008). Low MVC is associated with excellent (92%) long-term DFS. In those
      patients with high MVC, high nm23 allows the identification of a subgroup with
      significantly higher DFS (90% compared with 66%, P = 0.02). Among high nuclear
      grade tumors, if nm23 is high, the DFS is significantly better (89% compared with
      68%, P = 0.03). Thus, nm23 is still associated with excellent survival, even when
      there is unfavorable angiogenesis or nuclear grade. Multivariate analysis
      confirms that nm23 and MVC are important prognostic factors. High MVC appears
      necessary but not sufficient for metastasis to occur, whereas low nm23 may
      further contribute to metastatic progression. Both nm23 and MVC contribute
      valuable information in characterizing the malignant phenotype.

PMID- 9661890
TI  - Aspirin toxicity for human colonic tumor cells results from necrosis and is
      accompanied by cell cycle arrest.
AB  - Chemoprevention of colorectal cancer using aspirin has been demonstrated in
      rodents and has been suggested by data from epidemiological studies. The
      mechanism that accounts for this prevention is unknown, but it is thought to
      relate to an irreversible inhibition of cyclooxygenase and, subsequently,
      prostaglandin production. The effect of aspirin on the growth of human colonic
      tumor cells was determined in an effort to gain insight into a possible mechanism
      of action. In the two cell lines studied, SW 620 and HT-29, we observed a
      significant dose- and time-dependent increase in aspirin toxicity in a
      concentration range of 1.25-10 mM. This result was independent of prostaglandin
      production, because there was no measurable prostaglandin E2 in cell culture
      medium. As compared with controls, cells in cultures that contained aspirin were
      not detached, which suggests that the mechanism of cell death was not apoptosis.
      Flow cytometric analysis revealed an increase in S phase and G2-M populations as
      well as the number of subdiploid nuclei in cultures treated with high-dose
      aspirin. Confirmation that cells were undergoing necrosis in response to aspirin
      was evident from the presence of cells that bound annexin V and accumulated
      propidium iodide in the absence of a population that bound annexin alone. The
      results suggest that aspirin induces cell cycle arrest and causes necrosis at
      high concentrations in vitro, but does not induce apoptosis. Collectively, these
      two events, necrosis and cell cycle arrest, may contribute to the chemopreventive
      effect that seems to result from long-term administration of aspirin in vivo.

PMID- 9661891
TI  - Androgen-dependent and -independent human prostate xenograft tumors as models for
      drug activity evaluation.
AB  - The present study evaluated three human prostate xenograft tumors (CWR22, CWR22R,
      and CWR91) as models for drug activity evaluation. The chemosensitivity and the
      expression of several proteins (i.e., p-glycoprotein or Pgp, prostate specific
      antigen or PSA, p53, and Bcl-2) in xenograft tumors were compared with those in
      patient tumors obtained through radical prostatectomy (n = 26). CWR22 is androgen
      dependent, CWR22R is the androgen-independent subline of CWR22, and CWR91 is a
      separately derived androgen-independent tumor. The results of immunohistochemical
      and/or Western blot analysis indicate that the expression of PSA, Pgp, p53, and
      Bcl-2 in the three CWR xenograft tumors are representative of their expression in
      100, 85, 90, and 60%, respectively, of patient tumors. The responses of
      histocultures of xenograft tumors to doxorubicin and paclitaxel, including
      inhibition of DNA precursor incorporation and cell death induction, were
      qualitatively similar to the responses of patient tumors. For example, in all
      three xenograft and patient tumors, doxorubicin produced complete
      antiproliferation and cytotoxicity (ie., cell kill) whereas paclitaxel produced
      incomplete effects. A comparison of the concentration-effect relationships in
      xenograft and patient tumors (population median values) indicates that the
      chemosensitivity observed in patient tumors is represented by the
      chemosensitivity of one or more of the three xenograft tumors, as follows: (a)
      the three xenograft tumors and patient tumors responded equally to doxorubicin
      induced antiproliferation; (b) CWR22R, CWR91 and patient tumors responded equally
      to doxorubicin-induced cytotoxicity, whereas CWR22 was 2-3-fold less sensitive;
      (c) CWR22 and CWR22R tumors were less sensitive to paclitaxel-induced
      antiproliferation compared with patient tumors, whereas CWR91 was several-fold
      more sensitive; and (d) CWR22, CWR22R and patient tumors responded equally to
      paclitaxel-induced cytotoxicity, whereas CWR91 was 2-3-fold more sensitive. The
      results of this study indicate that the three xenograft tumors, which show
      chemosensitivity comparable with the results of > or =50% patient tumors and
      encompass the majority of the heterogeneous patient prostate tumors in the
      expression of Pgp, PSA, p53 and Bcl-2 proteins, are useful models for drug
      activity evaluation.

PMID- 9661892
TI  - Squalamine inhibits angiogenesis and solid tumor growth in vivo and perturbs
      embryonic vasculature.
AB  - The novel aminosterol, squalamine, inhibits angiogenesis and tumor growth in
      multiple animal models. This effect is mediated, at least in part, by blocking
      mitogen-induced proliferation and migration of endothelial cells, thus preventing
      neovascularization of the tumor. Squalamine has no observable effect on
      unstimulated endothelial cells, is not directly cytotoxic to tumor cells, does
      not alter mitogen production by tumor cells, and has no obvious effects on the
      growth of newborn vertebrates. Squalamine was also found to have remarkable
      effects on the primitive vascular bed of the chick chorioallantoic membrane,
      which has striking similarities to tumor capillaries. Squalamine may thus be well
      suited for treatment of tumors and other diseases characterized by
      neovascularization in humans.

PMID- 9661893
TI  - Phase I trial of intraperitoneal iododeoxyuridine with and without intravenous
      high-dose folinic acid in the treatment of advanced malignancies primarily
      confined to the peritoneal cavity: flow cytometric and pharmacokinetic analysis.
AB  - In this Phase I study, the maximally tolerated doses (MTDs) of i.p.
      iododeoxyuridine (IdUrd) alone and in combination with i.v. calcium leucovorin
      (LV) were determined. The pharmacokinetics and pharmacological advantage of IdUrd
      were evaluated, and flow cytometric analysis allowed examination of the extent of
      incorporation of IdUrd into tumor cells with and without the addition of i.v. LV.
      Thirty-nine patients with advanced neoplasms primarily confined to the peritoneal
      space were enrolled in a dose-escalation trial using 4-h dwells of IdUrd
      administered i.p. daily for 4 days with and without an i.v. infusion of LV 500
      mg/m2/day for 4.5 days. Twenty-three patients received single-agent therapy, and
      13 patients received i.p. IdUrd in combination with i.v. LV. The MTD of single
      agent IdUrd administered on this schedule was 4125 mg/m2/day for 4 days; and that
      of the IdUrd in combination was 3438 mg/m2/day. Dose-limiting toxicities were
      myelosuppression and stomatitis. During the period of the dwell, the peritoneal
      AUC (area under the curve) of IdUrd exceeded the plasma AUC of IdUrd by one or
      two orders of magnitude in all patients at all doses tested; there was a possible
      effect of LV on peritoneal AUC. The geometric mean pharmacological advantage
      (AUCperitoneal/ AUCplasma) was 181 at 625 mg/m2/day and 90 at 4538 mg/m2/day.
      Flow cytometric analysis suggests saturation of IdUrd measured in DNA at the 2500
      3125 mg/m2 dose level, without an increase after the addition of LV. Twelve
      patients received 4-12 courses of therapy. One patient with recurrent ovarian
      cancer who received 16 courses of therapy experienced complete resolution of her
      ascites, near normalization of CA-125 levels, and improved quality of life; two
      patients with high-risk tumors receiving "adjuvant" therapy are disease-free at 3
      and 6 years after treatment; other patients experienced transient clearing of
      ascites. The recommended Phase II dose of i.p. IdUrd using a 4-h dwell daily for
      4 days is 3750 mg/m2/day alone or 3125 mg/m2/day in combination with continuous
      i.v. LV at 500 mg/m2/day for 4.5 days. Although flow cytometric data suggest that
      DNA incorporation of IdUrd is not affected by the addition of LV, the
      cytotoxicity of the combination regimen may be increased due to LV-enhanced,
      IdUrd-related inhibition of thymidylate synthase. For this reason, we recommend
      that efficacy studies of the combination continue in parallel with studies of
      IdUrd alone.

PMID- 9661894
TI  - Death of tumor cells after intracellular acidification is dependent on stress
      activated protein kinases (SAPK/JNK) pathway activation and cannot be inhibited
      by Bcl-2 expression or interleukin 1beta-converting enzyme inhibition.
AB  - The extracellular microenvironment of tumors differs from that of most normal
      tissues. Many tumors have relatively acidic extracellular pH, although the
      intracellular pH of tumor cells remains normal due to the efficient maintenance
      of a large proton gradient across the membrane. This difference between tumors
      and normal tissues might be exploited therapeutically by disruption of the
      mechanisms that regulate intracellular pH, so that tumor cells are killed by
      intracellular acid-induced injury. To investigate the mechanisms by which
      intracellular acidification leads to cell death, we have studied the roles of the
      antiapoptotic gene bcl-2 and its proapoptotic binding partner bax, the stress
      activated protein kinases (SAPK/JNK), and the caspase proteases in mediating acid
      induced cell death. Whereas the expression of bcl-2 in human bladder cancer MGH
      U1 cells had no effect on acid-induced death, overexpression of bax enhanced cell
      death, consistent with its proapoptotic function. Inhibition of SAPK, through the
      expression of a dominant negative mutant of its activator, SEK1, protected cells
      from acid-induced cell death. Caspase activation, as measured by poly(ADP-ribose)
      polymerase cleavage, was absent after lethal intracellular acidification.
      Consistent with this observation, inhibition of interleukin 1beta-converting
      enzyme proteases by the peptide z-Val-Ala-Asp(OMe)-CH2F did not protect against
      acid-induced cell killing. We conclude that acid-induced cell death depends on
      bax and on SAPK signaling pathways, but not on the caspase proteases. Therapeutic
      manipulation of bax and SAPK may enhance acid-induced tumor cell killing.

PMID- 9661895
TI  - Sensitivity of K562 and HL-60 cells to edelfosine, an ether lipid drug,
      correlates with production of reactive oxygen species.
AB  - Edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine; ET-18-OCH3), a
      membrane-targeting anticancer ether lipid drug has been shown previously in vitro
      to be capable of initiating oxidative processes in cells. Here we study two human
      leukemia cell lines (HL-60 and K562) that have different sensitivities to
      edelfosine; HL-60 cells are more sensitive than K562 cells. To determine whether
      edelfosine alters the sensitivity of these lines to an oxidative stress, cells
      were subjected to the oxidative stress of iron(II) plus ascorbate and then
      monitored for free radical formation, membrane integrity, and cytotoxicity. The
      HL-60 cell was sensitive to the ether lipid drug in clonogenic and dye exclusion
      assays; a lipid-derived free radical was generated by this sensitive cell in the
      presence of small amounts of Fe2+ and ascorbate as detected by electron
      paramagnetic resonance and the spin trap alpha-(4-pyridyl-1-oxide)-N-tert
      butylnitrone. There was also simultaneous generation of an ascorbate-free
      radical, which has been shown to estimate cellular oxidative flux. In contrast,
      the K562 cell was resistant to edelfosine cytotoxicity in all assays and did not
      generate either lipid-derived or ascorbate-free radicals. Subcellular homogenates
      of the HL-60 cell generated both radicals when exposed to the drug, but
      homogenates of K562 did not generate either, suggesting that differential drug
      uptake or intracellular drug localization is not the cause of the difference in
      oxidation. Trypan blue uptake by the HL-60, but not the K562 cells, measured
      under the same conditions as the oxidation experiments, demonstrated a loss of
      membrane impermeability with similar time and concentration dependence,
      suggesting a causal relationship of membrane damage and radical generation.
      Complementary studies of HL-60 cell membrane integrity with propidium iodide
      impermeability and light scatter using the flow cytometer showed a concentration
      dependence that was similar to radical generation. Biochemical studies of the
      fatty acids of the HL-60 cell revealed more highly polyunsaturated lipids in the
      cells. Cellular antioxidant enzymes and vitamin E contents of the two cell lines
      were similar. We conclude that there is a time- and concentration-dependent
      generation of important oxidations by the sensitive HL-60 cells exposed to the
      membrane-targeted ether lipid, but the resistant K562 cells are oxidatively
      silent. This may be due in part to the differences in fatty acid polyunsaturation
      of the cellular membranes. The difference in oxidative susceptibility could be
      the basis for drug resistance to this membrane-specific anticancer agent.

PMID- 9661896
TI  - Explaining differences in sensitivity to killing by ionizing radiation between
      human lymphoid cell lines.
AB  - We surveyed five human hematopoietic cell lines (HSB-2, MOLT-4, Reh, CEM, and HL
      60) to determine whether any simple correlates with sensitivity to killing by
      gamma-irradiation might be revealed. The clonogenic survival gamma-ray dose
      response curves for these cell lines cover a wide range of sensitivities.
      Consistent with previous results for murine hematopoietic cell lines, there was a
      clear correlation between the rapidity with which irradiation induced apoptosis
      and clonogenic radiosensitivity of a cell line, although the relationship between
      timing of apoptosis and radiosensitivity differed between human and murine cell
      lines. Flow cytometric determination of cell cycle distribution after irradiation
      showed that differences between human hematopoietic cell lines, in the rate of
      induction of apoptosis, were generally related to the functioning of cell cycle
      checkpoints. Whereas the rapidly dying and radiosensitive HSB-2 cell line
      underwent apoptosis from different points in the cell cycle, the more slowly
      dying cell lines showed a variety of cell cycle arrest profiles and initiated
      apoptosis after accumulation of cells in the G2 phase. The lag-phase between
      arrest in G2 and induction of apoptosis was comparable for MOLT-4, Reh, and CEM;
      however, HL-60 cells showed a markedly longer G2 arrest that correlated with
      their greater radioresistance. The results suggest that the total length of time
      available for DNA damage repair (irrespective of whether this time accrues as
      blockage in G1, S, or G2), prior to potential activation of apoptosis, is a
      critical determinant of radiosensitivity in human hematopoietic cell lines.
      Comparison of the p53 status of these cell lines suggested that mutations in the
      TP53 gene are contributing to the delay of induction of apoptosis seen in the
      more radioresistant cell lines. The sensitivity of MOLT-4 and HL-60 cells to
      killing by DNA-associated 125I decays was determined and was found to correlate
      with the relative sensitivity of these lines to gamma-irradiation. The highly
      localized deposition of energy by 125I decays argues that DNA damage is a potent
      initiator of apoptosis in these cell lines. The results presented suggest that
      differences in the radiosensitivity of the cell lines examined reflect
      differences in the rapidity of induction of apoptosis and that radiation-induced
      cell death in hematopoietic cells can be explained as a response to DNA damage.

PMID- 9661897
TI  - Recombinant humanized anti-HER2 antibody (Herceptin) enhances the antitumor
      activity of paclitaxel and doxorubicin against HER2/neu overexpressing human
      breast cancer xenografts.
AB  - Recombinant humanized anti-HER2 antibody, rhuMAb HER2, inhibits the growth of
      breast cancer cells overexpressing HER2 and has clinical activity. We explored in
      preclinical models its capacity to enhance the tumoricidal effects of paclitaxel
      and doxorubicin. In cultures of naturally HER2-overexpressing cancer cells,
      rhuMAb HER2 inhibited growth and enhanced the cytotoxic effects of paclitaxel.
      Treatment of well established BT-474 breast cancer xenografts overexpressing HER2
      in athymic mice with rhuMAb HER2 resulted in a dose-dependent antitumor activity.
      In combination studies, treatment with paclitaxel and rhuMAb HER2 or doxorubicin
      and rhuMAb HER2 resulted in greater inhibition of growth than that observed with
      any agent alone. The combination of paclitaxel and rhuMAb HER2 resulted in the
      highest tumor growth inhibition and had a significantly superior complete tumor
      regression rate when compared with either paclitaxel or rhuMAb HER2 alone.
      Clinical trials that are built on these results are under way.

PMID- 9661898
TI  - IFN-gamma induces cell growth inhibition by Fas-mediated apoptosis: requirement
      of STAT1 protein for up-regulation of Fas and FasL expression.
AB  - The mechanism by which IFN-gamma inhibits tumor cell growth has not been fully
      understood. Here we report that IFN-gamma up-regulated the expression of Fas and
      Fas ligand (FasL) on HT29 cells, a human colon adenocarcinoma cell line, and
      subsequently induced apoptosis of these cells. The kinetics of cell death in IFN
      gamma-treated HT29 cells paralleled the increase in the levels of Fas and FasL
      expression. We further show that IFN-gamma up-regulated the expression of Fas and
      FasL in STAT1-transfected U3A cells but not in STAT1-deficient U3A cells.
      Correspondingly, IFN-gamma induced cell death in STAT1-transfected U3A cells but
      not in STAT1-deficient U3A cells. IFN-gamma-induced cell death was inhibited by
      caspase-1 inhibitors. Our results suggest that cell growth inhibition by IFN
      gamma is due to apoptosis mediated by Fas and FasL interaction.

PMID- 9661899
TI  - Effective adoptive immunotherapy by T-LAK cells retargeted with bacterial
      superantigen-conjugated antibody to MUC1 in xenografted severe combined
      immunodeficient mice.
AB  - To reinforce cytotoxic activity and the targeting ability of lymphokine-activated
      killer cells with a T-cell phenotype (T-LAK) for adoptive immunotherapy against
      human bile duct carcinoma (BDC), staphylococcal enterotoxin A (SEA) was
      conjugated chemically with MUSE11 monoclonal antibody (MUSE11 mAb), directed to
      the MUC1 antigen, using N-succinimidyl 3-(2-pyridyldithio) propionate and 2
      iminothiolane HCl. Both SEA-conjugated MUSE11 mAb (SEA-MUSE11) and the F(ab')2 of
      MUSE11 mAb (SEA-F(ab')2) showed significant enhancement of T-LAK cell tumor
      neutralization for MUC1 positive-target tumor cells, even with a concentration of
      0.01 microg/ml at an E:T ratio of 5:1 in vitro. In this in vitro test, MUC1
      positive BDC cells were observed to attach to surrounding T-LAK cells in the
      presence of SEA-MUSE11 or SEA-F(ab')2. Remarkable tumor growth inhibition was
      observed in BDC-grafted severe combined immunodeficient mice to which 2 x 10(7) T
      LAK cells preincubated with 2 microg of SEA-MUSE11 or SEA-F(ab')2, together with
      recombinant interleukin 2 (500 IU), were administered i.v. for 4 consecutive
      days, when tumor size was 5 mm in diameter. These results point to a promising
      adoptive immunotherapy for patients with BDC.

PMID- 9661900
TI  - Antibodies against GD2 ganglioside can eradicate syngeneic cancer
      micrometastases.
AB  - After 10 years of clinical trials in patients with advanced cancer, monoclonal
      antibodies (mAbs) against cell surface antigens have not lived up to their
      initial promise. One such cell surface antigen is the ganglioside GD2. GD2 is
      richly expressed at the cell surfaces of human neuroblastomas, sarcomas, and
      melanomas. We have described a murine lymphoma (EL4) that is syngeneic in C57BL/6
      mice and expresses GD2, a mAb against GD2 (mAb 3F8), and we have prepared a
      conjugate vaccine (GD2-keyhole limpet hemocyanin plus immunological adjuvant QS
      21) that consistently induces antibodies against GD2. We demonstrate here, for
      the first time in a syngeneic murine model, that passively administered and
      vaccine-induced antiganglioside antibodies prevent outgrowth of micrometastases,
      and we use this model to establish some of the parameters of this protection. The
      level of protection was proportional to antibody titer. Treatment regimens
      resulting in the highest titer antibodies induced the most protection, and
      protection was demonstrated even when immunization was initiated after tumor
      challenge. Treatment with 3F8 1, 2, or 4 days after i.v. tumor challenge was
      highly protective, but waiting until 7 or 10 days after challenge resulted in
      minimal protection. The results were similar whether number of liver metastases
      or survival was used as the end point. These results suggest that unmodified mAbs
      or antibody-inducing vaccines against GD2 (and possibly other cancer cell surface
      antigens) should be used exclusively in the adjuvant setting, where circulating
      tumor cells and micrometastases are the primary targets.

PMID- 9661901
TI  - Elevated frequencies of benzo(a)pyrene-induced Hprt mutations in internal tissue
      of XPA-deficient mice.
AB  - Xeroderma pigmentosum (XP) patients are hypersensitive to sunlight and have a
      high predisposition to developing cancer. At the cellular level, XP patients are
      defective in nucleotide excision repair (NER). Recently, mice have been generated
      via gene targeting that are deficient in the expression of the XPA gene [A. de
      Vries et al., Nature (Lond.), 377: 169-173, 1995]. We have assessed the
      consequences of defective NER for mutagenesis in normal and XPA mice exposed to
      benzo(a)pyrene and 2-acetylaminofluorene. To study mutagenesis, mature T
      lymphocytes were isolated from the spleen and stimulated to proliferate in vitro
      to select for mutants at the endogenous Hprt locus. Background mutant frequencies
      in normal and XPA mice were very similar and not influenced by age. Single doses
      of benzo(a)pyrene administered i.p. resulted in a dose-dependent increase of the
      Hprt mutant frequency in normal mice. In addition, after chronic exposure to
      benzo(a)pyrene, Hprt mutants were readily detectable in XPA mice at an early
      onset of treatment but only at a later stage in normal mice. In contrast, chronic
      treatment of either normal or XPA mice with 2-acetylaminofluorene did not
      increase Hprt mutant frequency above the background frequency. This absence of
      significant induction of Hprt mutants can be entirely attributed to the low
      frequency of 2-acetylaminofluorene-induced DNA adducts in lymphoid tissue. These
      results provide the first direct evidence in mammals that deficient NER leads to
      enhanced mutagenesis in endogenous genes in internal tissue after exposure to
      relevant environmental mutagens, such as benzo(a)pyrene.

PMID- 9661902
TI  - Chemically induced mutations in mitochondrial DNA of human cells: mutational
      spectrum of N-methyl-N'-nitro-N-nitrosoguanidine.
AB  - We have observed a reproducible mitochondrial mutational spectrum in the MT1
      human lymphoblastoid line treated with N-methyl-N'-nitro-N-nitrosoguanidine
      (MNNG). The MNNG spectrum was distinct from the spontaneous mutational spectrum.
      However, our ability to observe MNNG-induced mitochondrial mutations above the
      high level of accumulated spontaneous mutations was dependent on the MT1
      phenotype. MT1 cells are markedly resistant to the cytotoxicity but not the
      mutagenicity of MNNG, presumably as a result of inactivation of both copies of
      the hMSH6 (GTBP) mismatch repair gene. Thus, we were able to use conditions of
      treatment that yielded induced mitochondrial mutant fractions beyond the
      practical limits for human cell experiments in mismatch-proficient human cell
      lines. In contradistinction, when MT1 cells were treated repeatedly with maximum
      tolerated concentrations of (+/-) anti-benzo(a)pyrene diol-epoxide, no induced
      mitochondrial mutations above the spontaneous background were observed. A single
      dose of 4 microM MNNG (survival, 0.85) induced a mutant fraction of 8 x 10(-3) in
      the nuclear hypoxanthine-guanine phosphoribosyltrans. ferase gene, and a clear
      and reproducible pattern of seven MNNG-induced hotspot mutations was observed
      within the mitochondrial DNA target sequence studied (mitochondrial bp 10,030
      10,130). All of the MNNG-induced hotspot mutations were G:C to A:T transitions
      present at frequencies between 6 x 10(-5) and 30 x 10(-5). Additional experiments
      supported the conclusion that MNNG-induced hotspot mutations observed were
      generated in living cells as a result of MNNG treatment and not from mismatch
      intermediates or DNA adducts converted into mutations during the PCR process.

PMID- 9661903
TI  - Human chromosome 21 determines growth factor dependence in human/mouse B-cell
      hybridomas.
AB  - Interleukin 6 (IL-6) serves as a growth factor for mouse plasmacytomas. As a
      model for IL-6-mediated growth of plasmacytomas, we study IL-6-dependent B-cell
      hybridomas, which can be generated through fusion of B lymphocytes with a
      plasmacytoma cell line, e.g., SP2/0. In the present report, we have investigated
      the peculiar behavior of B-cell hybridomas with respect to IL-6 dependence. We
      demonstrate that although newly generated hybridomas are IL-6 dependent, many
      hybridomas lose this dependency at frequencies as high as 50%, shortly after
      fusion. We speculated that the loss of IL-6-dependent growth is due to the well
      known chromosomal instability of B-cell hybridomas. Consequently, loss of IL-6
      dependence is the result of loss of a specific chromosome(s). This model implies
      the existence of an "IL-6 dependency" gene, the loss of which makes hybridomas
      capable of proliferating in the absence of IL-6. Because SP2/0 is IL-6
      independent, the IL-6-dependent phenotype of B-cell hybridomas, and hence the IL
      6 dependency gene, must be derived from the B lymphocyte. We have tested this
      model by generating human/mouse B-cell hybridomas through fusion of human B
      lymphocytes with SP2/0. We then analyzed the human chromosome content of 10 IL-6
      dependent and 14 IL-6-independent subclones. From that analysis we concluded that
      the presence of human chromosome 21 correlated with IL-6 dependence. This
      correlation was confirmed by microcell fusion experiments in which a single copy
      of chromosome 21 was introduced into IL-6-independent hybridomas, resulting in
      reconstitution of the IL-6-dependent phenotype. We therefore conclude that
      chromosome 21 carries an IL-6 dependency gene.

PMID- 9661904
TI  - Mitochondrial membrane potential (delta psi(mt)) in the coordination of p53
      independent proliferation and apoptosis pathways in human colonic carcinoma
      cells.
AB  - We have previously defined depressed mitochondrial function as a determinant in
      colon cancer risk and progression and established that metabolism of butyrate, a
      short-chain fatty acid generated during the fermentation of fiber by endogenous
      intestinal bacteria, induces mitochondrial function-dependent growth arrest and
      apoptosis of colonic carcinoma cells in vitro. Here, we dissect the relationships
      among mitochondrial function, growth arrest, and apoptosis, reporting that
      initiation and maintenance of butyrate-mediated p53-independent p21WAF1/Cip1
      induction and subsequent G0/G1 arrest require an intact mitochondrial membrane
      potential (delta psi(mt)) and that the process of dissipation of the delta
      psi(mt) is then essential for initiation of a butyrate-induced apoptotic cascade.
      Thus, we hypothesize that mitochondria play a pivotal role in coordinating
      proliferation and apoptosis pathways, a coordination that must be tightly
      regulated in rapidly renewing tissues, such as the colonic mucosa.

PMID- 9661905
TI  - Frequent overexpression of the cyclin D1 oncogene in invasive lobular carcinoma
      of the breast.
AB  - Invasive lobular carcinoma comprises approximately 10% of human mammary cancers,
      yet little is known about the molecular basis of this carcinoma. Because cyclin
      D1 plays a role in the pathogenesis of breast carcinomas of the ductal type, we
      hypothesized that this confirmed oncogene might also participate in the
      development of lobular carcinomas. We sought to determine the frequency of cyclin
      D1 protein overexpression in invasive lobular carcinoma, to investigate the cause
      of the protein accumulation, and to identify the effects of high levels of the
      protein on the regulation of the cell cycle. The study group comprises 27
      indisputable cases of invasive lobular carcinoma showing varying degrees of
      cytological atypia. Immunohistochemical staining using well-characterized
      monoclonal and polyclonal antibodies disclosed cyclin D1 protein in the majority
      of the invasive lobular carcinoma cells in 80% of the tumors. In marked contrast,
      only rare cells of the noninvasive component (lobular carcinoma in situ) in the
      same tissue sections showed positive staining. Southern blotting of nine cases
      did not reveal evidence of cyclin D1 gene amplification. Immunohistochemical
      staining for Ki-67, a protein present in all dividing cells, showed that most
      cells positive for cyclin D1 did not stain for Ki-67. We conclude that the vast
      majority of invasive lobular carcinomas show overexpression of cyclin D1 protein.
      The absence of cyclin D1 protein expression in the noninvasive cells suggests
      that the molecule plays a role in the progression to the invasive form of lobular
      carcinoma. In contrast to the ductal types of breast cancer, cyclin D1 gene
      amplification does not seem to cause the cyclin D1 protein overexpression in
      lobular cancers. The lack of correlation between cyclin D1 and Ki-67 expression
      suggests that the cyclin D1 oncogene acts through mechanisms other than simple
      acceleration of the cell cycle clock in this subtype of human breast carcinoma.

PMID- 9661906
TI  - Progression of hepatic neoplasms is severely retarded in mice lacking the
      bisecting N-acetylglucosamine on N-glycans: evidence for a glycoprotein factor
      that facilitates hepatic tumor progression.
AB  - The glycosyltransferase termed GlcNAc-TIII is dedicated to the transfer of a
      single N-acetylglucosamine (GlcNAc) residue (the bisecting GlcNAc), to a subset
      of N-glycans in glycoproteins. The addition of this GlcNAc is differentially
      regulated during development and is induced in certain cancers, particularly in
      hepatic tumorigenesis. To investigate a functional role for the bisecting GlcNAc
      in the development of liver cancer, the Mgat3 gene that codes for GlcNAc-TIII,
      was inactivated by targeted gene disruption, and the susceptibility of Mgat3-/-
      mice to tumor induction was tested. After a single injection with
      diethylnitrosamine and subsequent treatment with phenobarbitol for 6 months,
      Mgat3+/+ and Mgat3+/- mice had grossly enlarged livers that contained numerous
      tumors. By stark contrast, Mgat3-/- mice had livers of normal size, and only 50%
      of mice had one to four small tumors. However, histological examination showed
      that Mgat3-/- livers had significant numbers of basophilic foci, and by 10-12
      months after diethylnitrosamine injection, tumors had developed in Mgat3-/- mice.
      Therefore, initiation occurred in Mgat3-/- mice but progression was severely
      retarded. Assays for Mgat3 gene expression in tumor tissue gave an unexpected
      result. In contrast to the situation in the rat, hepatic tumor formation in the
      mouse was not accompanied by a dramatic increase of GlcNAc-TIII activity nor of
      glycoproteins with a bisecting GlcNAc, nor of Mgat3 gene expression in tumor
      tissue from wild-type mice. The data suggest that a glycoprotein factor with the
      bisecting GlcNAc facilitates tumor progression in liver. In the absence of the
      bisecting GlcNAc in Mgat3-/- mice, the factor is reduced in activity, and tumor
      progression is severely retarded.

PMID- 9661907
TI  - p53 genes mutated in the DNA binding site or at a specific COOH-terminal site
      exert divergent effects on thyroid cell growth and differentiation.
AB  - Expression of mutated versions of the p53 gene deranged the differentiation
      program of thyroid cells and resulted in deregulated growth. Specifically, p53
      mutants in several residues of the DNA-binding region induced thyrotropin (TSH) 
      independent growth and inhibition of the expression of thyroid-specific genes.
      The loss of the differentiated phenotype invariably correlated with the blockage
      of the expression of the genes coding for the thyroid transcriptional factors PAX
      8 and TTF2. Conversely, thyroid cells transfected with a p53 gene mutated at
      codon 392, located outside the DNA-binding region, stimulated the expression of
      differentiation genes in the absence of the TSH, and induced TSH-independent
      growth. cAMP intracellular levels were higher in thyroid cells transfected with
      the p53 gene mutated at the 392 site than in the untransfected thyroid cells, but
      lower in the cells transfected with the other mutated p53 genes. Fra-1 and c-jun
      were induced by p53, resulting in increased AP-1 levels. The results of this
      study suggest that p53 exerts effects on cAMP transduction pathway in thyroid
      cells, which are exquisitely sensitive to cAMP.

PMID- 9661908
TI  - The University of California, Los Angeles/Jennifer Jones Simon Foundation
      symposium on prostate cancer and epithelial cell biology: bringing together basic
      scientists and clinicians in the fight against advanced prostate cancer.
AB  - Prostate cancer is the most common solid tumor in American men and is the second
      most common cause of cancer deaths. Although surgery and radiation therapy are
      effective for the treatment of organ-confined cancer, there is no effective
      treatment that is currently available for patients who have metastatic disease.
      Antiandrogen therapy is only palliative, and chemotherapy has largely been
      ineffective. However, recent advances in the understanding of the molecular
      biology of prostate cancer have lead to the development of new treatment
      strategies for metastatic cancer, including gene-based therapies,
      immunotherapies, and antiangiogenesis-based therapy. In association with the
      Jonsson Comprehensive Cancer Center and the University of California, Los Angeles
      Department of Urology, the Jennifer Jones Simon Foundation assembled 30 of the
      world's experts in prostate cancer research to review the most recent advances in
      the study of prostate cancer, with the hope that the resulting discussions would
      facilitate the rapid translation of new discoveries from the laboratory bench to
      the clinic.

PMID- 9661909
TI  - Urinary levels of inorganic and organic arsenic metabolites among residents in an
      arseniasis-hyperendemic area in Taiwan.
AB  - In order to elucidate whether urinary levels of inorganic and organic arsenic
      metabolites are associated with previous exposure to high-arsenic artesian well
      water, a total of 302 residents of age 30 yr or older were recruited from three
      arseniasis-hyperendemic villages in Taiwan. Most study subjects had stopped
      consuming high-arsenic artesian well water for more than 20 yr. The mean total
      arsenic (Ast) determined by inductively coupled plasma mass spectrometer (ICPMS)
      was 267.05 +/- 20.95 microg/L, and the mean level of inorganic arsenic and its
      metabolites (Asi) was 86.08 +/- 3.43 microg/L. In the multivariate analysis,
      urinary dimethylarsinic acid (DMA) levels were significantly inversely associated
      with age, with women exhibiting significantly lower urinary amounts of arsenite
      [As(III)], arsenate [As(V)], monomethylarsonic acid (MMA), organic arsenic (Aso),
      and Ast compared to men. After adjustment for age and sex, previous cumulative
      arsenic exposure through consumption of artesian well water was significantly
      associated with elevated urinary levels of MMA and DMA, but not As(III) + As(V),
      Aso and Ast. In the multivariate analysis, the percentage of Aso in Ast was
      significantly higher in men than women, but this was not significantly associated
      with age. The percentage of As(III) + As(V) in Asi increased significantly with
      age, while the reverse was noted with DMA in Asi. Women had a significantly
      higher DMA percentage but lower As(III) + As(V) and MMA percentages in Asi than
      men. After adjustment for age and sex, the percentages of As(III) + As(V) in Asi
      were significantly inversely associated with previous arsenic exposure through
      consumption of artesian well water. Data suggested that women seem to possess a
      more efficient arsenic methylation capability than men, and aging diminishes this
      methylation capability; furthermore, the higher the cumulative arsenic exposure,
      the greater is the body burden of inorganic arsenic, mainly in the form of MMA
      and DMA.

PMID- 9661910
TI  - Flow cytometric determination of metallothionein levels in human peripheral blood
      lymphocytes: utility in environmental exposure assessment.
AB  - Metallothioneins (MT) are ubiquitous, low-molecular-weight proteins that exhibit
      high binding affinities for heavy metal ions. The expression of these cysteine
      rich proteins is induced in response to various types of chemical and physical
      stresses and therefore can be used to assess human exposure to cytotoxic
      environmental agents. In the current study, MT levels of human peripheral blood
      lymphocytes were determined using an MT-specific antibody and flow cytometry.
      Treatment of human whole blood ex vivo with CdCl2 was found to induce a
      concentration- and time-dependent increase in lymphocyte MT levels at
      concentrations as low as 0.3 microM and within a 12-h period. Interestingly,
      differences were observed in the magnitude of cadmium-induced MT levels in the
      lymphocytes of six human test subjects. Two members of the study population
      exhibited CdCl2-induced cellular MT levels that were up to twofold greater than
      the lymphocytes of other human subjects. While the lymphocytes of most test
      subjects exhibited a symmetric (unimodal) distribution of cadmium-induced MT
      specific fluorescence, the cells of two individuals displayed a heterogeneous
      (nonuniform) distribution of MT levels. Dual-parameter flow cytometric analysis
      using phenotype-specific antibodies indicated that variations in the
      responsiveness of subpopulations of lymphocytes to CdCl2 were responsible for the
      heterogeneous distribution of MT-specific cellular fluorescence. T-helper (CD4
      positive) and T-suppressor/cytotoxic (CD8-positive) lymphocytes expressed higher
      cellular levels of MT than other lymphocyte subpopulations (i.e., B lymphocytes,
      natural killer cells). Our results suggest that MT protein levels of peripheral
      blood lymphocytes, as determined by this flow cytometric method, may be used to
      assess human exposure to toxic metals and to characterize various
      quantitative/qualitative aspects of the response of individuals to cadmium and
      possibly to other types of environmental stresses.

PMID- 9661911
TI  - Exposure of nonmigratory pigeons to mancozeb: a sentinel model for humans.
AB  - The use of pesticides in agriculture has increased over the last decade. Their
      widespread, often uncontrolled use causes thousands of people to be daily exposed
      to environmental agricultural chemicals, resulting in acute and chronic health
      effects. At present there is a paucity of data on the potential adverse effects
      of exposure to low levels of mancozeb for prolonged periods. In order to
      investigate the effects of mancozeb exposure on pulmonary wildlife populations,
      tracheas and lungs of nine 1- to 7-yr-old nonmigratory pigeons raised near peach
      orchards and vineyards repeatedly sprayed with the fungicide were examined. The
      experimental situation allowed us to evaluate the long-term natural toxicity of
      mancozeb as a sentinel for human populations occupationally exposed to
      fungicides. The use of nonmigratory pigeons may serve as an important biological
      source from which helpful data may be obtained for assessing risks to human
      health and gaining new insight into pathogenetic mechanisms.

PMID- 9661912
TI  - Prevention of pericyte loss by trolox in diabetic rat retina.
AB  - Prolonged hyperglycemia results in a number of diabetic complications, including
      retinopathy. Pericyte degeneration is one of the earliest histological changes
      observed in the development of diabetic retinopathy. Increased free radicals
      generated under hyperglycemia could damage the retina, which abounds in
      polyunsaturated fatty acids. In the current study, a severalfold increase in
      thiobarbituric acid-reactive substances was found in rat retina cultured in
      hyperglycemic medium, which decreased significantly when trolox, an amphipathic
      antioxidant, was included in the medium. To examine the contribution of oxidative
      stress in vivo, diabetic rats were fed trolox (0.4% in the diet) during the
      course of the experiments. After 5 mo of hyperglycemia, whole mounts of retinal
      vessels were prepared and endothelial cells (E) and pericytes (P) were counted.
      The ratio of E/P in the retinas obtained from normal rats, diabetic rats, and
      diabetic rats fed trolox were 1.74 +/- 0.186, 3.78 +/- 0.47, and 2.32 +/- 0.24,
      respectively. A significant restoration of pericytes by trolox suggests the
      involvement of oxidative injury during pericyte loss in diabetic retinopathy.

PMID- 9661913
TI  - Oxidative stress induced by humic acid solvent extraction fraction in cultured
      rabbit articular chondrocytes.
AB  - Kashin-Beck disease (KBD), an endemic, chronic osteoarthritic disorder with
      necrosis of chondrocytes, commonly occurs in China. The humic substance present
      in the drinking water of endemic areas has been proposed as one of the causative
      factors. In this study an in vitro cell culture system was used to investigate
      the damaging effects of humic acid (HA), a constituent of humic substance, on
      cultured rabbit articular chondrocytes. The commercial Aldrich humic acid (AHA)
      was fractionated with a series of organic solvents including n-hexane, benzene,
      ethyl acetate, and methanol. Among the several fractions of AHA, the ethyl
      acetate fraction (AHA-[EA]) displayed the most potent inhibitory effect on the
      survival of chondrocytes in clonogenic assays. Cellular injury induced by AHA
      [EA] was evaluated by measuring cell viability with methylthiazol tetrazolium
      (MTT) and by determining the release of intracellular lactate dehydrogenase
      (LDH). Incubation of chondrocytes with AHA-[EA] (100-500 microg/ml) for 12 h
      produced a concentration-dependent decrease in cell viability and increase in LDH
      release. In addition, AHA-[EA] triggered lipid peroxidation manifested by
      elevated malondialdehyde (MDA) formation. In chemiluminescence assay, AHA-[EA] at
      the concentrations of 150-600 microg/ml caused 6- to 15-fold increases of luminol
      amplified chemiluminescence responses, which are considered to reflect the
      production of hydrogen peroxide (H2O2). Moreover, pretreating the cells with 500
      750 U/ml of catalase significantly prevented the loss of cell viability, while
      superoxide dismutase (SOD) enhanced the adverse effect of 300 microg/ml AHA-[EA].
      Data suggest that the injury to chondrocytes induced by AHA-[EA] may be first
      through O2.- production, which is then converted into H2O2, thus initiating lipid
      peroxidation and leading to chondronecrosis observed in KBD.

PMID- 9661914
TI  - Inhibition of respiratory and bioenergetic mechanisms by hydrogen sulfide in
      mammalian brain.
AB  - The biochemical effects of hydrogen sulfide were investigated by treating enzyme
      homogenates and synaptosomes prepared from mammalian brain with sodium sulfide.
      Brain cytochrome c oxidase activity was highly sensitive to inhibition by sodium
      sulfide, as demonstrated by an IC50 of 0.13 microM. Sodium sulfide was also found
      to inhibit carbonic anhydrase activity in cerebellum, frontal cortex, and
      hippocampus. Synaptosomal oxygen consumption was significantly reduced as the
      concentration of sodium sulfide was increased from 20 to 100 microM; this was
      accompanied by a concentration-dependent depolarization of the synaptosomal
      mitochondrial membrane in situ and a reduction in synaptosomal ATP concentration.
      In other experiments using synaptosomes, sodium sulfide caused a significant
      calcium-independent increase in the extracellular accumulation of L-glutamate,
      inhibited Na+-dependent uptake of [3H]glutamate, but was unable to influence
      intrasynaptosomal free ionic Ca2+. Parallel studies conducted in vivo showed that
      rats exposed over a 5-d period to hydrogen sulfide (100 ppm for 3 h/d) had
      significantly higher concentrations of L-glutamate in the hippocampus compared to
      control animals. In summary, our results indicate that sulfide causes extensive
      disruption to respiratory and related mitochondrial functions in mammalian brain
      in vitro. The reduced capacity of nerve endings to take up L-glutamate may
      contribute to the raised L-glutamate levels observed in vivo.

PMID- 9661915
TI  - Striking a balance: Tissue harvesting for prostate cancer research.

PMID- 9661916
TI  - Prostatectomy tissue for research: balancing patient care and discovery.
AB  - The application of modern technology in basic research often requires fresh
      tissue from human organs. The acquisition of this tissue challenges the anatomic
      pathologist to balance the needs of the basic scientist with the requirements of
      quality patient care. Our experience indicates that fresh tissue adequate for
      research can be obtained from neoplastic prostate glands without compromising
      patient care. The process requires dedicated, knowledgeable individuals and
      extensive documentation. Potential problems include low yield for research
      studies, loss of all residual carcinoma, compromise of the specimen margin, and
      unforeseen costs. Best collaborations occur in situations in which basic
      scientists and anatomic pathologists establish a working relationship and develop
      a mutually supportive means of funding.

PMID- 9661917
TI  - The cytologic features of Wegener's granulomatosis.
AB  - To evaluate the role of cytopathology and its different sampling techniques in
      the diagnosis of Wegener's granulomatosis, we retrospectively reviewed 52
      cytologic specimens from 21 patients with an established diagnosis of Wegener's
      granulomatosis. The smear background, cellular composition, and accompanying
      reactive changes were evaluated. The majority of the smears were characterized by
      a bloody background with necrotic debris and extensive acute inflammation. Large
      sheets of exfoliated reactive pneumocytes and bronchial epithelium were commonly
      present. Multinucleated giant cells and epithelioid histiocytes were present in
      10 and 20 specimens, respectively. Numerous hemosiderin-laden histiocytes were
      present in variable numbers in most cases and were abundant in 15 cases.
      Bronchial brush and lavage were the best sampling techniques. Although fine
      needle aspiration best demonstrated the granulomas, only 2 of the 6 aspirates
      were diagnostic. The combination of cytologic findings, negative cultures, and
      elevated titers of antineutrophil cytoplasmic antibody with a cytoplasmic pattern
      may serve to establish a presumptive diagnosis of Wegener's granulomatosis.

PMID- 9661918
TI  - Analysis of p53, p21WAF1, and TGF-beta1 in human ductal adenocarcinoma of the
      pancreas: TGF-beta1 protein expression predicts longer survival.
AB  - Loss of p53 and p21WAF1 expression have previously been reported in pancreatic
      adenocarcinoma. Despite these findings in several reports of oncogene and tumor
      suppressor gene alterations in pancreatic cancer, the clinical significance of
      these changes is still poorly understood. In an attempt to detect molecular
      prognostic markers for pancreatic carcinoma, we studied the immunohistochemical
      expression of p53, p21WAF1, and TGF-beta1 proteins in 42 pancreatic
      adenocarcinomas of the ductal type. The results were correlated with
      clinicopathologic findings to identify the markers with prognostic significance.
      p53 nuclear immunoreactivity was seen in 20 (48%) of the cases, and it was strong
      to moderate in 14 (33%) of them. p21WAF1 cytoplasmic positivity was found in 16
      (38%) of the tumors, with 72% staining strong to moderate. TGF-beta1 stained the
      cytoplasm of the tumor cells in 13 (31%). Of the p53-negative cases, 12 (54%)
      exhibited p21WAF1 expression. In 3 (30%) of cases, TGF-beta1 reactivity was seen
      in the absence of p53 and p21WAF1 p53 positivity identified tumors of higher
      grade, but did not correlate with stage or survival. TGF-beta1 expression,
      however, identified low-grade tumors and patients with longer survival. No
      correlation was found between the expression of any of these molecular markers
      and smoking history. We report a significant correlation between TGF-beta1
      reactivity and low-grade tumors and between TGF-beta1 and better survival. This
      is a novel finding pointing to TGF-beta1 as a possible new stage-independent
      predictor of tumor survival in pancreatic ductal adenocarcinoma. In agreement
      with others, we also found p53 mutation in 20 (48%) of the tumors.

PMID- 9661919
TI  - Positivity of the proliferation marker Ki-67 in noncycling cells.
AB  - Ki-67 is a proliferation marker that is often used to estimate the growth
      fraction of tumors and other tissues. This antigen is expressed during all phases
      of the cell cycle but not in quiescent G0 cells. Many studies fail to indicate
      that the Ki-67 antigen can be expressed even when DNA synthesis is blocked. We
      studied the expression of the antigen Ki-67 in cycle-arrested osteosarcoma cells.
      We found that these cells are positive for Ki-67 even when they are arrested in
      G1/S or G2/M by using synchronizing inhibitors, by inducing p21(Waf1/Cip1) in a
      tetracycline-regulated expression system or by inducing wild type p53 and p21
      after inflicting DNA damage. Our results show that not all cells containing the
      Ki-67 antigen are actively proliferating cells and we advise against the use of
      Ki-67 in studies on cells that overexpress p53 or p21.

PMID- 9661920
TI  - Immunohistochemical detection of hepatitis C antigen by monoclonal antibody
      TORDJI-22 compared with PCR viral detection.
AB  - We sought to determine the sensitivity and specificity of immunohistochemistry
      using the TORDJI-22 MoAb (BioGenex, San Ramon, Calif), which is specific for the
      C-100 protein of the hepatitis C virus, compared with reverse transcriptase
      polymerase chain reaction (RT-PCR) of tissue for viral RNA. RT-PCR had been
      performed on 52 fixed tissue specimens. Immunohistochemistry was performed using
      prediluted antibody with the alkaline phosphatase/fast red (BioGenex) technique.
      Predigestion with Protease XXIV (BioGenex) and other procedures followed the
      manufacturer's protocols. Positive immunohistochemistry was narrowly defined as
      tightly clumped, perinuclear red granules in hepatocytes. Of the specimens, 28
      were positive by RT-PCR. With RT-PCR as the standard of comparison,
      immunohistochemistry yielded a sensitivity of 70% and specificity of 84%.
      Positive cells, when present, were usually very rare. With stringent criteria,
      immunohistochemistry with the TORDJI-22 monoclonal antibody is a very specific,
      fairly sensitive diagnostic test for hepatitis C virus in fixed liver tissues.

PMID- 9661921
TI  - Correlation of gross morphologic features with histologic features in radical
      prostatectomy specimens.
AB  - The gross features of prostatic adenocarcinoma can be subtle. While these gross
      features have been described, the histologic correlates have not been detailed.
      This study involved examination of 211 consecutive radical prostatectomy
      specimens between January 1995 and December 1996. The gross findings were
      correlated with histologic examination. No gross lesion was apparent in 47 cases
      (22.3%), a subtle lesion was present in 78 (37.0%), and a definite lesion
      suggestive of carcinoma, in 86 (40.8%). Tumor was identified grossly and
      confirmed histologically in 50 (64%) of 78 subtle lesions, 83 (96%) of 86
      definite lesions, and in 63% of all prostatectomy specimens. Prostatectomy
      specimens with definite lesions were significantly more likely to contain tumors
      that were stage T3 or higher (37%) than those with a subtle lesion (20%), were
      higher grade (mean Gleason score, 6.8 vs 6.36), and had larger tumor diameters
      (mean, 1.3 cm vs 1.0 cm). Specimens with subtle lesions were more likely to
      contain tumors that were stage T3 or higher compared with specimens with no
      apparent gross lesions (20% vs 4%), but did not differ significantly in mean
      Gleason score (6.36 vs 6.26) or tumor size (1.0 cm vs 0.95 cm). Ninety-two
      percent of all tumors stage T3 or higher, 81% of all tumors Gleason score 8 or
      higher, and 72% of all tumors greater than 1.0 cm in diameter were grossly
      identified and confirmed histologically. However, the site of extraprostatic
      extension and positive margins were present in the histologic sample of the
      grossly identified lesion in only 27 (54%) of 50 cases and 20 (46%) of 43 cases,
      respectively. Prostatic adenocarcinomas can be accurately identified by gross
      inspection in 63% of cases; the false-positive rate for gross inspection was 19%.
      The presence of an identifiable gross lesion is correlated with increased tumor
      stage, grade, and size.

PMID- 9661922
TI  - An initial trial of a prototype telepathology system featuring static imaging
      with discrete control of the remote microscope.
AB  - Routine diagnosis of pathology images transmitted over telecommunications lines
      remains an elusive goal. Part of the resistance stems from the difficulty of
      enabling image selection by the remote pathologist. To address this problem, a
      telepathology microscope system (TelePath, TeleMedicine Solutions, Birmingham,
      Ala) that has features associated with static and dynamic imaging systems was
      constructed. Features of the system include near real time image transmission,
      provision of a tiled overview image, free choice of any fields at any desired
      optical magnification, and automated tracking of the pathologist's image
      selection. All commands and images are discrete, avoiding many inherent problems
      of full motion video and continuous remote control. A set of 64 slides was
      reviewed by 3 pathologists in a simulated frozen section environment. Each
      pathologist provided diagnoses for all 64 slides, as well as qualitative
      information about the system. Thirty-one of 192 diagnoses disagreed with the
      reference diagnosis that had been reached before the trial began. Qf the 31, 13
      were deferrals and 12 were diagnoses of cases that had a deferral as the
      reference diagnosis. In 6 cases, the diagnosis disagreed with the reference
      diagnosis yielding an overall accuracy of 96.9%. Confidence levels in the
      diagnoses were high. This trial suggests that this system provides high-quality
      anatomic pathology services, including intraoperative diagnoses, over
      telecommunications lines.

PMID- 9661923
TI  - Soft tissue sarcomas: the usefulness and limitations of fine-needle aspiration
      biopsy.

PMID- 9661924
TI  - Comparison of cardiac troponin I, creatine kinase-MB, and myoglobin for detection
      of acute ischemic myocardial injury in a swine model.
AB  - To study the comparative value of the levels of cardiac troponin I (cTnI),
      creatine kinase-MB isoenzyme (CK-MB), and myoglobin in the detection of acute
      ischemic myocardial injury, we serially measured plasma concentrations of these
      cardiac proteins in 12 pigs with myocardial ischemia subtending severe coronary
      artery stenoses and in 5 pigs with a sham operation performed, but without
      coronary artery stenosis. In the stenosis group, flow in the left anterior
      descending (LAD) artery was reduced by 36% and maintained for 24 hours (n = 3), 7
      days (n = 6), or 4 weeks (n = 3). Flow in the coronary artery was measured by a
      flowmeter, and regional left ventricular dysfunction was monitored by
      echocardiography. Myocardial infarction was identified with triphenyltetrazolium
      chloride staining. All pigs with stenosis of the LAD had significant
      ultrastructural abnormalities consisting of loss of myofibrils and an increase in
      mitochondria and glycogen deposition. Cardiac proteins were released in all pigs
      with stenosis of the LAD artery during the development of myocardial ischemia;
      the levels of cTnI, CK-MB, and myoglobin increased significantly relative to the
      baseline. The sensitivity and specificity for cTnI were higher than for CK-MB or
      myoglobin. Results of this study show that cTnI is the better marker for the
      detection of acute ischemic myocardial injury. Increased levels of cTnI can be
      found in reversible and irreversible myocardial ischemic injury in this model.

PMID- 9661925
TI  - Unexpected suppression of total digoxin concentrations by cross-reactants in the
      microparticle enzyme immunoassay: elimination of interference by monitoring free
      digoxin concentration.
AB  - The microparticle enzyme immunoassay (MEIA for digoxin (Abbott Laboratories,
      Abbott Park, Ill) requires no sample pretreatment and is widely used in clinical
      toxicology laboratories for monitoring serum digoxin concentrations. One
      advantage of the new MEIA is the lower cross-reactivities with such cross
      reactants as digitoxin, oleandrin, and bufalin compared with the fluorescence
      polarization immunoassay (FPIA)for digoxin. Digitoxin, oleandrin, and bufalin
      showed positive cross-reactivity with MEIA and FPIAs for digoxin in the absence
      of the primary analyte, digoxin. A surprising finding was that digoxin
      concentrations were falsely decreased by these cross-reactants when serum pools
      containing digoxin were supplemented with various concentrations of these cross
      reactants and when digoxin concentrations were measured by the MEIA. In contrast,
      digoxin concentrations were falsely elevated when measured by the FPIA. For
      example, when a serum pool containing 2.15 nmol/L of digoxin was supplemented
      with 129.5 nmol/L of bufalin, the apparent digoxin concentrations were 1.45
      nmol/L with the MEIA and 3.00 nmol/L with the FPIA. Taking the advantage of only
      25% protein binding of digoxin and more than 95% protein binding of digitoxin and
      bufalin, we demonstrated that monitoring free digoxin instead of total digoxin
      eliminated negative interference of digoxin by these cross-reactants in the MEIA
      and positive interference in the FPIA. Although oleandrin is also strongly bound
      to serum protein, high concentrations of oleandrin still modestly affect the free
      digoxin assay for both MEIA and FPIAs.

PMID- 9661926
TI  - Multidimensional flow cytometry of marrow can differentiate leukemic from normal
      lymphoblasts and myeloblasts after chemotherapy and bone marrow transplantation.
AB  - Serial bone marrow aspirates from patients previously given a diagnosis of acute
      lymphoblastic leukemia (ALL) who had undergone chemotherapy, bone marrow
      transplantation (BMT), or both were analyzed by multidimensional flow cytometry
      (MDF) to detect residual disease (lower limit of detection 0.3%). Correlation
      between the results of morphologic examination and MDF showed concordant results
      on 100 of 118 specimens. The MDF-positive, morphologic examination-negative
      specimens were positive by cytogenetic examination or were obtained from patients
      in whom the ALL eventually relapsed. Similar correlations between MDF and the
      results of cytogenetic examination were obtained. Leukemic cells were detected in
      29 of 62 patients before BMT and 12 of 52 after BMT Normal regenerating
      lymphoblasts were identified and quantified by MDF in patients without detectable
      leukemic lymphoblasts. Patients with leukemic lymphoblasts found by MDF in
      specimens obtained immediately before BMT were 3.28 times more likely to
      experience relapse after BMT compared with MDF-negative patients, even when
      leukemic lymphoblasts were undetectable by histopathologic examination,
      cytogenetic examination, or both. All patients who had undergone BMT with
      leukemic lymphoblasts found by MDF, with or without morphologic or cytogenetic
      confirmation, experienced relapse according to conventional criteria within 42
      days of the MDF analysis. The detection of residual disease before overt relapse
      may provide information for early intervention, while definitive recognition of
      normal recovering blasts may prevent unnecessary treatment.

PMID- 9661927
TI  - Follicular large cell lymphoma with immunoblastic features in a child with
      Wiskott-Aldrich syndrome: an unusual immunodeficiency-related neoplasm not
      associated with Epstein-Barr virus.
AB  - Patients with Wiskott-Aldrich syndrome, a severe inherited immunodeficiency
      disorder, have a markedly increased risk of developing non-Hodgkin's lymphoma
      compared with the general population. These are uniformly diffuse aggressive B
      cell neoplasms that resemble those seen in AIDS and the posttransplantation
      setting and also may be associated with Epstein-Barr virus. We report what to our
      knowledge is the first case of follicular lymphoma in a 14-year-old child with
      Wiskott-Aldrich syndrome. The neoplasm was composed predominantly of large cells
      with immunoblastic features, and it possessed light chain-restricted surface
      immunoglobulin, clonal immunoglobulin gene rearrangements, and a t(14;18). The
      tumor lacked Epstein-Barr virus sequences by in situ hybridization and Southern
      blot terminal repeat analysis. Interestingly, however, the tumor contained c-myc
      gene rearrangement.

PMID- 9661928
TI  - Autologous blood donation by patients who have undergone solid organ
      transplantation.
AB  - Autologous blood donation before elective surgery is generally believed to be a
      safe procedure for patients with a variety of underlying medical conditions, but
      the accumulation of additional data continues to define its safety in unique
      patient groups. Patients who have received a solid organ transplant may also
      undergo various elective surgical procedures after transplantation, and the
      question of safety of autologous blood donation for these patients is raised. In
      one hospital-based blood collection program, we identified 4 patients who had
      received solid organ transplants and subsequently made autologous blood donations
      for elective operations unrelated to the transplantation. Two patients had
      received heart transplants and 2 received liver transplants. A total of 10
      autologous donations were made by these 4 patients without adverse effects or
      complications. A low hemoglobin concentration was the only reason for temporary
      deferral from autologous donation. Despite having complicated clinical
      situations, recipients of solid organ transplants can safely donate autologous
      blood and should not be automatically excluded from making such donations.

PMID- 9661929
TI  - Effect (or lack of it) of severe anemia on PT and APTT results.
AB  - Whether it is necessary to adjust the citrate volume in blood collection tubes
      for patients with anemia is unknown; however, the standard of care is not to
      adjust the volume. We compared the prothrombin time (PT) and activated partial
      thromboplastin time (APTT) test results of nonadjusted and adjusted citrate
      amounts in specimens from patients who are severely anemic. Samples were drawn
      into a 3.8% citrate volume, and if the hematocrit was less than 25% (0.25),
      additional samples were drawn into adjusted citrate tubes. The PT and APTT were
      run on 78 pairs of specimens, and the correlation coefficient was 0.98 for both
      assays. A statistically significant difference was noted between sample results
      collected in evacuated tubes in which the citrate volumes were adjusted to the
      hematocrit vs those in which it was not. However, when the difference between
      sets of values was plotted against the hematocrit, there was no correlation.
      There seems to be no need to change the standard practice for obtaining
      coagulation specimens into 3.8% citrate for patients who are anemic.

PMID- 9661930
TI  - The basics of antiretroviral prescribing.

PMID- 9661931
TI  - Should we be stopping opportunistic infection prophylaxis in the era of HAART?

PMID- 9661932
TI  - Acute rheumatic fever.

PMID- 9661933
TI  - Extended spectrum beta-lactamases.

PMID- 9661934
TI  - A model of human cutaneous candidosis based on reconstructed human epidermis for
      the light and electron microscopic study of pathogenesis and treatment.
AB  - The use of reconstructed human epidermis provided the basis for an in vitro model
      of human cutaneous candidosis. Candida albicans blastospores on the surface of
      reconstructed human epidermis provoked the following changes within 72 h:
      superficial keratin degradation, scaling, hyperkeratosis, parakeratosis,
      dyskeratosis representing hyperproliferative stress, spongiosis, and
      vesiculation. Great differences in the intensity of these reactions of intact
      reconstructed human epidermis or chemically or mechanically damaged reconstructed
      human epidermis illustrate the importance of the stratum corneum as a barrier.
      Uninfected reconstructed human epidermis showed prominent cell proliferation
      representing wound healing 72 h after mechanical or chemical pretreatment. These
      signs of repair were blocked in the presence of C. albicans and the blastospores
      were able to invade the stratum corneum. When desmosomes were accessible, a high
      affinity of C. albicans blastospores to these structures was observed. A single
      application of an econazole liposome dispersion decreased scaling, hyperkeratosis
      and dyskeratosis. Morphological alterations of C. albicans blastospores after
      treatment with the econazole liposome dispersion in the proposed ill vitro model
      were identical, as described in established animal models. This reconstructed
      human epidermis model of cutaneous disease may provide insight into the
      pathogenesis and treatment of cutaneous candidosis and may provide a substitute
      for animal models and investigations on humans.

PMID- 9661935
TI  - Yersinia enterocolitica and the chronic fatigue syndrome.
AB  - OBJECTIVES: To investigate the potential role of Yersinia enterocolitica in
      patients with chronic fatigue syndrome (CFS). METHODS: An immunoblot technique
      was used to detect antibodies to various Yersinia outer membrane proteins (YOPs)
      in serum samples from 88 patients with CFS and 77 healthy neighbourhood controls,
      matched for gender and age. RESULTS: The prevalence of IgG and IgA antibodies to
      various Yersinia outer membrane proteins (YOPs) did not differ between patients
      with CFS and healthy controls. Twenty-four patients (27%) and nineteen controls
      (25%) had IgG antibodies to one or more YOPs. Four patients and two controls had
      both serum IgG and IgA antibodies to at least two different YOPs, compatible with
      a recent or persistent infection. Although all patients with positive IgG and IgA
      reactions to two or more YOPs had symptoms that could point to persistent
      Yersinia infection, these symptoms were also found frequently in patients without
      antibodies to YOPs. CONCLUSIONS: We conclude that Y. enterocolitica is unlikely
      to play a major role in the aetiology of CFS.

PMID- 9661936
TI  - Detection of Mycobacterium tuberculosis in serum samples using the polymerase
      chain reaction.
AB  - Conventional methods for the diagnosis of Mycobacterium tuberculosis infections
      have serious limitations. To determine whether amplification of M. tuberculosis
      DNA in serum by the polymerase chain reaction (PCR) might be a useful additional
      diagnostic tool, we tested 329 clinical specimens using primers specific for the
      IS6110 insertion sequence of the M. tuberculosis complex. The samples consisted
      of 30 serum samples from healthy controls, 114 serum samples from patients with
      diagnoses other than tuberculosis (including immunosuppressive disorders), 59
      samples from patients with a clinical picture suggestive of tuberculosis, and 78
      serum samples from patients with proven M. tuberculosis infection. Both serum,
      and representative samples from anatomical regions suspected of being infected,
      were collected from a further 48 patients for comparison with serum PCR. Serum
      PCR identified 72/78 (92%; 95% confidence interval CI: 84%-97%) patients with
      proven tuberculosis, and 49/59 (83%; 95% CI: 71%-92%) patients with suspected
      tuberculosis. In the group of patients with other diagnoses, 30/114 (26%; 95% CI:
      18%-34%) tested positive, while none of the specimens from the healthy control
      group were positive (95% CI: 0%-12%). Serum PCR results also compared favourably
      with other clinical specimens obtained from the same patient. Serum PCR can,
      therefore, be a useful additional technique for the early diagnosis of M.
      tuberculosis infection, but it does not necessarily indicate active infection.

PMID- 9661938
TI  - Community-acquired Clostridium difficile infection.
AB  - Clostridium difficile-associated disease (CDAD) is primarily a nosocomial
      condition. Community-acquired disease has been reported but the incidence is felt
      to be low and the rate of disease resulting in hospitalization is reported as
      negligible. We recently experienced a 6-month outbreak of CDAD (January to June
      1995): 139 patients were involved and four deaths were attributable to
      pseudomembranous colitis. Early in the outbreak period we were aware that many
      new admissions presented with C. difficile cytotoxin B positive diarrhoea: in
      some cases this was the sole reason for hospitalization. This observation forms
      the basis of this report.

PMID- 9661937
TI  - The molecular and clinical epidemiology of enterobacteriaceae-producing extended
      spectrum beta-lactamase in a tertiary care hospital.
AB  - To describe the epidemiology of Enterobacteriaceae-producing extended-spectrum
      beta-lactamase (EP-ESBL) in a non-outbreak setting, and to define the risk
      factors associated with colonization, a 5-month surveillance study was initiated.
      Ten of 333 patients were colonized with EP-ESBL, as defined by isoelectric
      focusing. Klebsiella sp. and Escherichia coli were the species most commonly
      harbouring these plasmid-mediated enzymes. Of the 16 SHV-producing isolates, 10
      were SHV-3-like (pI 7.0) and six were SHV-5-like (pI 8.2). All isolates were
      resistant to ceftriaxone. Ceftazidime resistance was detected in 50% and 100% of
      SHV-3-like and SHV-5-like producing isolates, respectively. One patient was
      colonized with four different SHV-5-like producing Enterobacteriaceae. These
      isolates carried plasmids that were indistinguishable by restriction endonuclease
      analysis, indicating broad plasmid transfer within the patient. By logistic
      regression, haemodialysis was a strong risk factor for colonization with EP-ESBL,
      suggesting that, in our hospital, horizontal transmission is an important
      mechanism of dissemination of these resistant pathogens.

PMID- 9661939
TI  - Reactive arthritis following an outbreak of Salmonella Bovismorbificans
      infection.
AB  - A large, single-source Salmonella outbreak caused by a rare serovar
      Bovismorbificans (6,8:r:1,5) occurred in southern Finland in 1994. The origin of
      the outbreak was sprouted alfalfa seeds. A questionnaire was mailed to all 210
      subjects with positive stool culture. Ninety-one percent (191/210) returned the
      questionnaire. One hundred and fifty-three (80%) were adults. One hundred and
      fifty-nine out of one hundred and ninety-one (83%) reported diarrhoea, 109 (57%)
      fever, 104 (54%) abdominal pains, 83 (43%) fatigue, 66 (35%) articular symptoms
      and 20 (10%) had no symptoms. The median duration of diarrhoea was 5 days (range
      1-35), that of other symptoms 4 days (range 1-30). Those reporting articular
      symptoms were examined (51 patients) or contacted by telephone (13 patients).
      Twelve percent (22/191) fulfilled the criteria for reactive arthritis (ReA). The
      difference in the incidence of ReA between children and adults was not
      significant (8%, vs. 12%). The median onset of joint symptoms was 8.5 days;
      symptoms were oligoarticular in 14 (67%) and polyarticular in four (19%)
      patients. Mostly ReA was mild, but in four patients (18%) the joint symptoms
      lasted for more than 4 months. Ten (45%) ReA patients had HLA-B27 tissue type.
      The duration and severity of ReA did not differ between HLA-B27 positive and
      negative patients. Fourteen (64%) ReA patients had received fluoroquinolone
      treatment before reactive joint or tendon symptoms manifested, but this treatment
      did not prevent ReA symptoms.

PMID- 9661940
TI  - Central nervous system brucellosis: presentation, diagnosis and treatment.
AB  - Although neurological symptoms in brucellosis are frequent, central nervous
      system (CNS) involvement is uncommon. Five patients with neurobrucellosis are
      presented. Three patients presented with meningoencephalitis, one with
      polyradiculoneuritis and one with myelitis and an eighth nerve palsy. All
      patients had lymphocytic pleocytosis, low glucose and elevated levels of protein
      in the cerebrospinal fluid (CSF). Gamma-globulin and IgG values in the CSF were
      also increased. Results of agglutination tests for Brucella in serum and CSF were
      positive for all patients, although titres were less in the CSF. Brucella
      melitensis was cultured from two patients. Treatment included concurrent
      administration of three of the following drugs: doxycycline, rifampicin,
      streptomycin, co-trimoxazole, ceftriaxone or ciprofloxacin. The three patients
      with meningoencephalitis fully recovered; the other two patients were left with
      minor disability.

PMID- 9661941
TI  - Tuberculosis is the commonest cause of pneumonia requiring hospitalization during
      Hajj (pilgrimage to Makkah).
AB  - The diagnosis and treatment of pneumonia in mass gathering situations is a
      medical challenge, requiring prompt decision making and knowledge of the
      aetiology. We studied cases of pneumonia admitted to two hospitals during the
      1994 pilgrimage (Hajj) season to Makkah. Sixty-four patients were enrolled in the
      study, of which 47 (75%) were men with a mean age of 63 years (range 21-91).
      Nearly all were from developing countries. Diagnosis was established in 46
      patients (72%) with Mycobacterium tuberculosis being the commonest causative
      organism (20%), followed by gram-negative bacilli (18.8%). Streptococcus
      pneumoniae accounted for only 10%, with Legionella pneumophilia, Mycoplasma
      pneumoniae, and viruses accounting each for 6%. The main finding of this study is
      that M. tuberculosis is a common cause of pneumonia under these unusual "extreme
      circumstances". Its presentation was acute and indistinguishable from pyogenic
      pneumonia. Thirty-one per cent of tuberculous cases had upper lobe involvement,
      54% lower lobe, and 15% multi-lobar. This was similar to the radiographic
      features in non-tuberculous pneumonia cases. All but one patient with
      tuberculosis recovered following the administration of first-line anti
      tuberculous drugs. The total mortality was 17%. The preponderance of M.
      tuberculosis and Gram-negative bacteria over S. pneumoniae may reflect the prior
      use of amoxycillin and the effect of exhaustion, malnutrition, and old age.

PMID- 9661942
TI  - The decline in CD4+ T lymphocytes as a function of the duration of HIV infection,
      age at seroconversion, and viral load.
AB  - BACKGROUND: The rate of CD4+ T-lymphocyte decline seen in HIV-infected patients
      is very variable. Although older patients, a longer duration of HIV infection,
      and a high level of plasma viraemia, have been associated with a faster fall in
      CD4+ T-cells, the relationship between these variables is still not well known.
      PATIENTS AND METHODS: In a cross-sectional study that included a total of 107
      patients of known age and date at HIV seroconversion, the current CD4+ T-cell
      count and plasma viraemia were examined. Patients were not taking antiretroviral
      drugs, nor had received immunizations nor were suffering any intercurrent
      infections at the time of the study. RESULTS: The mean duration of HIV infection
      was 8.6+/-2.9 years. The mean CD4+ T-lymphocyte count was 367+/-264 x 10(6)/l.
      Mean plasma viraemia was 4.3+/-0.9 logs. In a linear regression model, the
      current CD4+ T-cell count was explained in 21.7% by the duration of HIV
      infection, while the level of plasma viraemia justified separately up to 37.0%.
      When both parameters were combined, they explained 58.8%. of the CD4+ lymphocyte
      values. In this model, a variation of one logarithm in the plasma viraemia had
      six times greater effect on the number of CD4+ lymphocytes than each year of HIV
      infection. When the age at seroconversion was added to the model, the CD4+ cell
      count allowed the explanation of up to 62.2% of cases. CONCLUSIONS: The age at
      seroconversion, the duration of HIV infection, and the level of plasma viraemia
      independently and substantially influence the current CD4+ lymphocyte count in
      HIV-infected subjects. However, other variables should exist (e.g. virus
      syncytium-inducing phenotype, host immunogenetic repertoire, etc.), contributing
      to explaining the different rate of CD4+ T-cell decline seen in HIV-infected
      subjects.

PMID- 9661943
TI  - Necrotizing fasciitis caused by Vibrio vulnificus differs from that caused by
      streptococcal infection.
AB  - We reviewed the clinical record of all patients admitted to Saga Medical School
      Hospital during the most recent 10 years and found that 17 (0.03%) were diagnosed
      as having necrotizing fasciitis. Bacteriological examination demonstrated that
      Vibrio vulnificus was the pathogen responsible in five patients (29%). The
      disease caused by V. vulnificus occurred in the warmer half of the year. All of
      the patients had underlying chronic liver dysfunction, and three of them had
      previously consumed raw seafood. In these patients, the predominant skin lesions
      were oedema and subcutaneous bleeding, such as ecchymosis and purpura, while
      superficial necrosis was not recognized. Three patients died of systemic
      complications. By contrast, all of the five patients with necrotizing fasciitis
      caused by Streptococcus pyogenes had the disorder in winter, and only one of them
      had chronic liver dysfunction. In skin lesions, subcutaneous bleeding was rare
      but necrosis was seen often. Despite the high incidence of systemic
      complications, no patients with streptococcal necrotizing fasciitis died. These
      findings suggest that the clinical features of necrotizing fasciitis caused by V.
      vulnificus are different from those of necrotizing fasciitis caused by classical
      pathogens, and that the two should be differentiated as early as possible to
      improve the prognosis.

PMID- 9661944
TI  - Environmental risk factors for sporadic Escherichia coli O157 infection in
      Scotland: results of a descriptive epidemiology study.
AB  - The objective of the study was to obtain detailed descriptive epidemiological
      information on sporadic verocytotoxin-producing Escherichia coli O157 infection
      in Scotland in relation to transmission routes and host-related risk factors.
      Using a standardized questionnaire, the study was carried out throughout Scotland
      over an 18-month period from July 1992 and co-ordinated at the Communicable
      Diseases and Environmental Health (Scotland) Unit, Glasgow (CDEH(S)U). The
      subjects were laboratory-confirmed cases of Escherichia coli O157 infection, of
      whom 138 met the criteria for inclusion in the study. The most important findings
      were the high proportion of cases who had been exposed to environmental factors
      such as farm animals and/or their by-products; or who had participated in
      gardening or garden-play; or who had suspected or confirmed household water
      supply problems, prior to the onset of illness. The frequency and relative
      importance of environmental risk factors requires further quantification and
      study in order to assess where control measures can be directed most effectively.
      The implications for the NHS in preventing this crippling, life-threatening
      infection are considerable, not least in relation to hospitalization, dialysis
      and renal transplantation costs.

PMID- 9661945
TI  - Successful treatment of Aspergillus fungaemia in two children with acute
      lymphoblastic leukaemia.
AB  - Aspergillus species can cause life-threatening infection in immunocompromised
      children. Pulmonary infections are the most common, and are usually acquired
      through inhalations of aspergillus spores in unfiltered air. Some patients
      acquire invasive aspergillus infection from endogenous spread of colonized para
      nasal sinuses.

PMID- 9661946
TI  - RP59500 (Quinupristin/dalfopristin): three case reports of its use in infection
      due to Enterococcus faecium.
AB  - We describe three cases of Enterococcus faecium sepsis arising in
      immunocompromised patients, severely ill with other conditions, who were treated
      with the new injectable streptogramin RP59500. There are still few reports of
      clinical experience with this drug. All had bacteriological resolution, with one
      patient recovering fully. Although two of the three patients died, this was due
      to underlying disease in one case and a gram-negative superinfection in another.
      Quinupristin/dalfopristin therapy was not associated with significant adverse
      effects in any of the patients.

PMID- 9661947
TI  - A case of Guillain-Barre syndrome associated with human parvovirus B19 infection.
AB  - We report a 4-year-old boy who presented with Guillain-Barre Syndrome 11 days
      after the onset of erythema infectiosum. The illness resolved without gamma
      globulin therapy.

PMID- 9661948
TI  - Microscopy and latex antigen negative cryptococcal meningitis.
AB  - A HIV-positive patient presented with cryptococcal meningitis that was not
      detected by cerebrospinal fluid (CSF) latex antigen and direct microscopy. The
      diagnosis was confirmed by culture of the CSF and subsequent urine culture, both
      of which yielded an apparently acapsular strain of Cryptococcus neoformans. After
      19 months the patient relapsed and capsulated yeasts were observed on this
      occasion on direct microscopy of the CSF. The latex antigen test was strongly
      positive. Culture again yielded an apparently acapsular isolate. Retrospective
      culture of all isolates obtained from this patient in sterile CSF resulted in the
      formation of capsules. This was confirmed by the requirement of normal non heat
      inactivated serum for neutrophil-cryptococcus attachment to occur in vitro.
      Although antigen and direct microscopy are frequently relied upon to diagnose
      cryptococcal meningitis, a negative result does not exclude the condition.

PMID- 9661949
TI  - Ecthyma gangrenosum in a patient with hypogammaglobulinemia.
AB  - Ecthyma gangrenosum is a characteristic skin lesion that is caused by Pseudomonas
      aeruginosa (P. aeruginosa) in the majority of cases. Systemic P. aeruginosa
      usually complicates debilitating conditions like leukaemia, burns and cystic
      fibrosis. We report a patient with underlying hypogammaglobulinemia who developed
      ecthyma gangrenosum secondary to P. aeruginosa septicaemia, which was potentially
      life-threatening. Recognition of the characteristic skin lesions with prompt
      initiation of appropriate antibiotics and intravenous immunoglobulins were life
      saving. A review of the English literature reports three other cases of ecthyma
      gangrenosum in patients with underlying hypogammaglobulinemia.

PMID- 9661950
TI  - Brain abscesses caused by Burkholderia pseudomallei.
AB  - Burkholderia pseudomallei is an important human pathogen in tropical areas,
      particularly South East Asia and Northern Australia. A fatal case of meliodosis
      presenting as brain abscesses is described. The patient deteriorated despite
      treatment and died 21 days after admission. Burkholderia pseudomallei was only
      isolated after administration of corticosteroids, whilst on treatment with
      antibiotics to which the organism later showed in vitro sensitivity. Magnetic
      resonance imaging was more sensitive than computed tomography in diagnosing early
      brainstem infection in this patient. Physicians working outside the endemic areas
      must be attuned to the possibility of melioidosis in any patient with an
      appropriate history of travel to endemic areas. The combination of striking
      early, extensive, confluent T2 hyperintensity with disproportionately small
      enhancing lesions may be characteristic of meliodosis.

PMID- 9661951
TI  - Do amoebic liver abscesses start as large lesions? Case report of an evolving
      amoebic liver abscess.
AB  - Amoebic liver abscesses (ALA) are characteristically large lesions at
      presentation, but their development in man has not previously been described. We
      present a case of an ALA that over the course of 2 days developed from an
      undetectable lesion to a 5 cm diameter lesion. This clinical history suggests
      that the pathogenesis of ALAs may pursue an acute rather than a chronic course.

PMID- 9661952
TI  - Postanginal septicaemia (Lemmiere's disease) complicated by haemophagocytosis.
AB  - We report a case of postanginal septicaemia complicated by bronchopneumonia and
      haemophagocytosis in a 19-year old male, presenting with severe thrombocytopenia.
      We believe that this is the first reported case of thrombocytopenia due to
      haemophagocytosis in this unusual condition.

PMID- 9661953
TI  - Infective endocarditis associated with upper endoscopy: case report and review.
AB  - We describe a 73-year-old male who developed native valve infective endocarditis
      due to Staphylococcus capitis as a consequence of repeated oesophageal
      dilatation. The patient was treated with appropriate antibiotic therapy but his
      condition deteriorated and he died. We review 10 previously reported cases of
      infective endocarditis associated with upper endoscopy and discuss the issue of
      prophylaxis of high risk patients prior to upper endoscopy involving various
      invasive procedures, e.g. biopsy, dilatation and sclerotherapy.

PMID- 9661954
TI  - Fatal cerebral oedema associated with primary dengue infection.
AB  - Encephalopathy associated with dengue fever is considered to be a rare condition
      in adults. We describe a patient with a primary dengue infection who, in the
      absence of overt signs of dengue shock syndrome, died due to progressive cerebral
      oedema. Autopsy findings demonstrated loss of integrity of cerebral vascular
      endothelium and involvement of complement activation.

PMID- 9661955
TI  - Penicillin resistance in Streptococcus pneumoniae isolated in the Balcali
      Hospital in Adana, Turkey.

PMID- 9661956
TI  - Prosthetic valve endocarditis caused by a vancomycin-resistant Enterococcus
      faecalis.

PMID- 9661957
TI  - Non-Acanthamoeba amoebic infection.

PMID- 9661958
TI  - Fresh orange juice implicated in an outbreak of Shigella flexneri among visitors
      to a South African game reserve.

PMID- 9661959
TI  - Symmetrical peripheral gangrene following perineal wound infection.

PMID- 9661960
TI  - Ralstonia pickettii involved in spinal osteitis in an immunocompetent adult.

PMID- 9661961
TI  - Rifabutin appears to be a promising agent for combination treatment of AIDS
      related toxoplasma encephalitis.

PMID- 9661962
TI  - Fatal myocarditis associated with a Lancefield group B streptococcus.

PMID- 9661963
TI  - Incidence of beta-lactamase production by oral aerobic/anaerobic flora from
      patients admitted for elective tonsillectomy.

PMID- 9661964
TI  - Non-progressive congenital ataxias.
AB  - Congenital ataxias (CA) are rare, predominantly non-progressive syndromes
      characterized by marked hypotonia, developmental delay followed by the appearance
      of ataxia. Most children show marked speech and cognitive developmental problems.
      Non- progressive CA (NPCA) can be divided into pure CA without additional
      symptoms and syndromes with CA. Pure CA can be due to cerebellar malformations as
      (hereditary or non-hereditary) cerebellar hypoplasia, Dandy Walker syndrome, or
      occasionally supratentorial abnormalities. Ataxic syndromes are less frequent,
      but more distinctive. There are syndromes (e.g. Joubert syndrome) where ataxia is
      a cardinal feature and others where ataxia is only an occasional symptom.
      Acquired ataxias, due to congenital cytomegalovirus infection or perinatal
      problems, form a small third group. In about half of all cases with NPCA,
      aetiology and inheritance are still unknown. Diagnosis of NPCA is made by a
      typical history and careful clinical examination. Diagnosis of a more distinctive
      ataxic syndrome may be possible on clinical grounds. Neuroimaging with special
      attention to the posterior fossa will aid accurate clinical classification. Early
      progressive ataxias require careful differentiation from other types.

PMID- 9661965
TI  - CT and MR imaging of cerebral tuberous sclerosis.
AB  - Tuberous sclerosis is a heredofamilial neurocutaneous syndrome, or phakomatosis,
      with multisystem involvement including the brain, kidney, skin, retina, heart,
      lung, and bone. The brain is the most frequently affected organ in tuberous
      sclerosis. Brain lesions in tuberous sclerosis are of three kinds; cortical
      tubers, white matter abnormalities, and subependymal nodules. We review the
      computed tomography (CT) and magnetic resonance (MR) features of the brain
      lesions in patients with tuberous sclerosis. CT clearly demonstrates calcified
      subependymal nodules. MR imaging demonstrates more clearly cortical, and white
      matter lesions than CT, since MR imaging shows excellent image contrast between
      various normal structures and high sensitivity in detecting pathological states
      due to intrinsic differences in proton density and in particular, in proton
      relaxation times of tissues. Possible pathogenesis of this disorder is also
      discussed.

PMID- 9661966
TI  - Qualitative changes of anticonvulsant action of felbamate during development in
      rats.
AB  - The anticonvulsant action of felbamate (25, 50, 100 and 150 mg/kg i.p.) was
      tested against motor seizures induced by pentylenetetrazol in five age-groups of
      rats (7, 12, 18, 25 and 90 days old). In adult rats, felbamate suppressed
      generalized tonic-clonic seizures leaving intact minimal clonic seizures. In all
      groups of rat pups felbamate exhibited a specific action against the tonic phase
      of generalized tonic-clonic seizures. In addition, the highest dose of felbamate
      was found to suppress minimal seizures in 18-day-old rats. The changes of
      felbamate action during ontogeny might be due to multiple mechanisms of
      anticonvulsant action with an uneven developmental profile.

PMID- 9661967
TI  - Childhood autism: the need for physical investigations.
AB  - In this paper the results of an extensive medical investigation of 25 children
      with childhood autism are presented and compared with those found in a group of
      non-autistic individuals matched for sex, age and intellectual level, all
      referred for developmental deviancy of unknown etiology. The examination included
      a psychiatric assessment and a neurological examination in addition to
      neurophysiological, chromosomal, metabolic and neuroimaging evaluation. In the
      clinical examination macrocephaly was found only among the autistic individuals,
      while the frequency of pathological cerebral CT and clinical parameters such as
      tendon reflexes and mobility problems was significantly greater in the control
      group. All the other pathological findings were found to occur with the same
      frequency in the two groups. Except for research purposes this study did not lend
      support to those who argue for extensive medical examinations for all children
      with autism. Based on the present findings, ordinary procedures for assessment of
      developmentally delayed children should be followed. This should include a
      systematic clinical neuropaediatric examination, an assessment of vision and
      hearing and a chromosome study, including that for fragile X.

PMID- 9661968
TI  - Maturational change of KCl-induced Ca2+ increase in the rat brain synaptosomes.
AB  - To investigate maturational change in the susceptibility of voltage-dependent
      calcium (Ca2+) channels (VDCC) in the brain to excessive depolarization, which is
      likely to occur during hypoxia or ischemia, we studied depolarization-induced
      increases in Ca2+ concentration in cortical synaptosomes ([Ca2+]i) obtained from
      young (8, 15, 22, 36, and 43-day-old) and adult rats using fura 2-AM as a Ca2+
      indicator. The effects of Ca2+ antagonists on the increase were also studied. The
      maximal increase in [Ca2+]i caused by 50 mM KCl-induced depolarization was
      significantly lower in 8-day-old rats (73.3 nM) compared with that in adult rats
      (133.6 nM). On the other hand, the time necessary for [Ca2+]i to decrease to 50%
      of its maximal level (tau) was significantly shorter in immature rats compared
      with that in adult rats and was particularly short in 8- and 15-day-old rats
      (0.28 and 0.40 min vs. 3.85 for adult rats). The maximal increase in [Ca2+]i in
      22-day-old rats and tau in adult rats were markedly reduced by verapamil, omega
      agatoxin IVA, and omega-conotoxin GVIA (antagonists of L-, P-, and N-type Ca2+
      channels, respectively) to similar extents, while a mixture of the three
      antagonists markedly decreased both maximal increase and tau in 8- and 22-day-old
      and adult rats. These results indicate that depolarization-induced Ca2+ influx
      through VDCCs in immature rat brain is less pronounced than that in adult rats,
      and suggest that the susceptibility of all of L-, N-, and P-type Ca2+ channels is
      increased during maturation in the first few weeks after birth. This lower
      susceptibility to depolarization might be involved in the resistance to hypoxia
      in immature animals.

PMID- 9661969
TI  - Gelastic epilepsy, hypothalamic hamartoma, precocious puberty, and agenesis of
      the corpus callosum: a new association.
AB  - We describe a boy who has gelastic epilepsy, precocious puberty, hypothalamic
      hamartoma, and agenesis of the corpus callosum. We believe that this is the first
      documented case in which agenesis of the corpus callosum has been associated with
      hypothalamic hamartoma and gelastic epileptic syndrome in a child.

PMID- 9661970
TI  - Congenital ataxia of parietal origin? Report of two cases.
AB  - Congenital cerebellar ataxia is usually thought to be of cerebellar origin. We
      report two children with congenital cerebellar ataxia, in whom neuroimaging
      investigations suggest the possibility of a parietal etiology. The two boys
      showed hypotonia, delayed motor and cognitive development followed by marked,
      truncally pronounced ataxia. In one case infantile spasms were treated
      successfully with adrenocorticotropic hormone, although in follow-up the child
      suffered from occasional seizures. Magnetic resonance imaging showed in one case
      parieto-occipital pachygyria and in the other there was marked pachygyria, most
      pronounced over the parieto-occipital area. In both children cerebellar
      structures were normal. Cerebello-parietal connections are known to be
      responsible for acquired parietal limb ataxia. Although not proven, parietal
      lesions are the most likely etiology of congenital cerebellar ataxia in these two
      children. Therefore, cerebral, especially parietal pathology must be considered
      in children with congenital ataxia.

PMID- 9661971
TI  - Slowly progressive cystic leukoencephalopathy with megalencephaly in a Japanese
      boy.
AB  - A Japanese boy with megalencephaly and leukoencephalopathy was reported. The
      clinical characteristics were as follows; slowly progressive megalencephaly
      starting at 8 months, and motor impairment with ataxia and spasticity, with
      relatively preserved intelligence and well-controlled epilepsy, and the following
      MRI findings; diffuse leukoencephalopathy in the supratentorial white matter with
      cystic subcortical white matter in the temporal tips and the fronto-parietal
      lobes. This corresponds to vacuolating leukoencephalopathy with megalencephaly,
      which was recently reported in European countries. In Japan, there were similar
      case reports previously, however, the patients were diagnosed as having
      Alexander's disease. It seems that this new leukoencephalopathy must also be seen
      among Japanese.

PMID- 9661972
TI  - Balo's concentric sclerosis in a 4-year-old Japanese infant.
AB  - We report the youngest known case with Balo's concentric sclerosis (Balo's
      disease), a variant of multiple sclerosis. This 4-year-old Japanese boy was
      diagnosed by clinical manifestations and by characteristic findings on magnetic
      resonance imaging (MRI). Dexamethasone was given intravenously, 3 mg twice daily
      for 10 days. The clinical manifestations were resolved within 2 weeks, and the
      MRI findings were markedly improved after 3 weeks. Following the initiation of
      steroid therapy, he showed remarkable clinical and physical improvement. It
      cannot be excluded that the clinical improvement resulted from the steroid
      therapy.

PMID- 9661973
TI  - Clinical and stabilometric monitoring in a case of cerebellar atrophy with
      vitamin E deficiency.
AB  - The authors describe a case of early onset ataxia with cerebellar atrophy and
      vitamin E deficiency, treated with alpha-tocopherol supplementation and
      physically rehabilitated by postural biofeedback. Clinical assessments, serum
      vitamin E levels and postural evaluation by means of a stabilometric platform
      continued for about 2 years and significant clinical improvement was recorded.
      Our study confirms that combined physical therapy and vitamin E supplementation
      may result in improvement of cerebellar function. Motor improvement is directly
      related to vitamin E serum levels, providing further confirmation that normal
      vitamin E levels are crucial for proper brain functions.

PMID- 9661974
TI  - Seizures and epileptic activity.

PMID- 9661975
TI  - High-fat diets and stress responsivity.
AB  - Adult male rats were fed one of five diets varying in fat composition (Purina
      Chow or soy bean oil, corn oil, menhaden oil, or olive oil added to chow) for 10
      weeks. After 3 days of access, no differences between groups were found in plasma
      corticosterone measured at light onset and light offset. During Week 2, restraint
      stress tests were performed. High-fat diets promoted significantly higher
      stimulated corticosterone levels. During Week 6 all rats were given an oral
      glucose tolerance test. Rats fed the corn and soybean oil diets had significantly
      elevated blood glucose 2 h after glucose intubation. Euglycemia was restored
      after 3 hours in all but the soybean oil group. During Week 9, a second stress
      test was performed. No differences in initial stress responsivity was observed,
      but groups fed the menhaden, soybean and olive oil diets had significantly higher
      corticosterone 1 h after the end of restraint. The corn oil, olive oil and
      soybean oil diets promoted transient hyperphagia. By the end of the experiment,
      the group fed the menhaden oil diet weighed significantly less and ate less than
      the remaining groups. These data demonstrate that stress responsivity is briefly
      enhanced during initial access to the high-fat regimens. Continued high-fat
      feeding results in an impaired ability to restore basal corticosterone following
      stress.

PMID- 9661976
TI  - Short-term growth: evidence for chaotic series of mini growth spurts in rat
      growth.
AB  - Five thousand and eighteen quadruplet daily measurements of lower-leg length of
      62 female and 81 male rats, were performed in order to characterize short-term
      growth. Within a short time, growth proceeds irregularly and consists of multiple
      incremental bursts (mini growth spurts) with no evidence for strict periodic
      behavior. Mini growth spurts are S-shaped incremental patterns that can be
      characterized by double-exponential functions (Gompertz's functions). Gompertz's
      functions are S-shaped, and can be defined by three parameters that identify
      amplitude, inflection point (age at peak growth velocity), and slope. The latter
      not only refers to the rapidity of each incremental burst, but also alludes to
      the duration that one incremental burst needs for completion. In regard to these
      characteristics, mini growth spurts differ significantly between the sexes in
      rats. Mean amplitude of mini growth spurts was 2153 microm (SD 1034 microm) in
      female rats and 2958 microm (SD 1614 microm) in male rats. Peak growth velocity
      of mini growth spurts appeared lower in male rats than in female rats. Female
      rats showed mean gamma of -1.23 (SD 0.72), whereas male rats showed mean y of 
      0.96 (SD 0.72). Partial growth hormone deficiency led to a modification in rats
      that was reversed when exogenous growth hormone was administered. Mean intervals
      between subsequent mini growth spurts ranged between 4.2 and 4.6 days, but the
      large variation of these intervals (SD between 1.6 and 2.3 days) and the fact
      that neither spurt-spurt interval nor spurt amplitude appeared predictable,
      strongly suggest chaotic behavior of mini growth spurts.

PMID- 9661977
TI  - Behavioral assessment of the senescence-accelerated mouse (SAM P8 and R1).
AB  - Senescence-accelerated mice (SAM P8 and R1) were behaviorally assessed in a cross
      sectional study at 4 and 15 months of age. Behavioral measures included memory
      (place discrimination and repeated acquisition in a water maze), sensorimotor
      performance (turning in an alley, traversing bridges, wire rod hanging, and falls
      from a wire screen), psychomotor performance (open-field exploration), and
      emotionality (entries in a plus maze, grooming, and defecation in a plus maze and
      in an open field). In the water maze, aged P8 mice were impaired in place
      discrimination and in repeated acquisition tasks, demonstrating evidence of an
      age-related decline in spatial memory processing abilities. The demonstration of
      this impairment, however, was complicated by noncognitive factors, such as the
      tendency of many older P8 mice to float. Sensorimotor skill impairment was
      accelerated with age in P8 mice, but not in R1 mice, and this impairment was
      present despite the lack of age-related changes in body weight in P8 mice.
      Although P8 and R1 mice were not different in general activity at old age, P8
      mice were substantially more hyperactive in an open field and in the plus maze
      than R1 mice when compared at young age. Independent of age, P8 mice demonstrated
      a reduction of anxiety-like behavior in the plus maze. Taken as a whole, the data
      suggest that although age-related behavioral alterations occur in the P8 mice,
      some of these changes are evident at 4 months of age. Thus, the behavioral
      abnormalities that exist not only represent an accelerated aging phenomenon but
      may also be considered a developmental pathology.

PMID- 9661978
TI  - Feeding-induced tonic pain suppression in the chicken: reversal by naloxone.
AB  - Endogenous analgesia induced by changes in motivation has been identified in the
      chicken in previous studies but either the motivational changes were difficult to
      interpret or the motivation was unpredictable. Experimental sodium urate (SU)
      arthritis of the ankle joint resulted in pain-coping behaviour (one-legged
      standing or sitting) for a 2-h period in non-food-deprived birds without access
      to food. Complete analgesia or marked hypoalgesia was observed in birds which had
      been food deprived overnight and given access to food immediately after SU
      injection. This analgesia seen during feeding behaviour in the food-deprived bird
      could be completely reversed by intravenous injection of naloxone. These results
      demonstrate that feeding motivation can totally suppress, in some animals, the
      severe tonic pain of SU arthritis and that this analgesia may be opioid mediated.

PMID- 9661979
TI  - Plasma testosterone levels are related to various aspects of locomotor activity
      in wild-caught male meadow voles (Microtus pennsylvanicus).
AB  - The relationship between plasma testosterone levels and locomotor activity in
      wild-caught sexually mature male meadow voles (Microtus pennsylvanicus) was
      assessed in the laboratory. Several aspects of locomotor activity were monitored
      for 1 h on two consecutive days using the automated Digiscan activity monitoring
      system. Plasma testosterone levels were determined immediately following the
      second day of activity monitoring. Significant Pearson correlations were obtained
      between plasma testosterone levels and total distance traveled [r(10) = 0.55, p <
      0.05] and amount of time spent in movement [r(10) - 0.55, p < 0.05] on the second
      day. The wild voles showed a reduction in activity levels from the first to the
      second day of activity monitoring, which is indicative of habituation to a novel
      environment. This study provides direct evidence for a significant correlation
      between laboratory measures of behavioral activity and plasma testosterone levels
      in a wild-caught rodent. These findings indicate that previous assessments of
      hormone-behavior relationships in laboratory-bred rodents are consistent with the
      relationship between hormones and behavior in wild rodents.

PMID- 9661980
TI  - Measuring gustatory variation in mice: a short-term fluid-intake test.
AB  - A short-term fluid-intake test is described which is directed at the study of
      individual variation in gustation in laboratory mice. To avoid position
      preferences associated with two-bottle tests, single graduated cylinders are used
      to present the solution. Intake of water and solutions is recorded for a 6-h
      period beginning 3 h prior to the dark phase of the light cycle. The timing of
      data collection ensures a stable baseline of fluid intake because it coincides
      with the period in which mice begin to drink. Food and water are available ad
      lib. at all other times so the test avoids the water restriction that is often
      used in gustatory studies. We report normative data on ten commonly used inbred
      strains for sucrose (100 mM), saccharin (10 mM), quinine (1.1 mM), HCI (1 and 3
      mM). NaCl (320 mM), and monosodium glutamate (150 mM). Strain differences were
      pronounced for all tastants. Concurrent measures of food and fluid intake by
      C57BL/6J and DBA/2J mice demonstrated that the short-term reduction of fluid
      intake resulting from 6-h quinine administration, which was restricted to
      C57BL/6J mice, was associated with a minor reduction in food intake during the 6
      h test and had no statistically significant effect on food or fluid intake during
      the 18-h post-test period or during a 6-h period the next day. The absence of
      large-scale or persistent nonspecific effects supports the use of the paradigm
      for screening of multiple solutions on the same animals. The reliability of the
      test is supported by positive correlations between repeated measurements of the
      same solution across substantial time intervals. Its ease of use, substantial
      reliability, and avoidance of water restriction make the test a very useful
      addition to screening tools in the field of gustation research.

PMID- 9661981
TI  - NaCl appetite in two strains of rat reported to be resistant to mineralocorticoid
      induced hypertension.
AB  - Both Long-Evans (LE) and Wistar-Furth (WF) strains of rat are known to be
      resistant to development of hypertension by mineralocorticoid (MC) treatment. MC
      induced hypertension is, in part, mediated by the brain. We have examined another
      aspect of central MC action, the induction of NaCl appetite in these strains, by
      using the more common Sprague-Dawley (SD) and Wistar (WS) strains for comparison.
      In the first experiment, LE and SD rats were administered three treatments known
      to induce an appetite for NaCl solution in rats. Administration of
      deoxycorticosterone acetate (DOCA) increased the intake of 0.45 M NaCl in both
      strains, but the amounts consumed were about 2-fold greater in LE rats than in SD
      rats. Administration of captopril also increased NaCl intake, but there were no
      differences between LE and SD rats. NaCl depletion with furosemide induced NaCl
      appetite in both strains, but the amounts consumed were about 2-fold greater in
      LE rats than in SD rats. In the second experiment, adult male WF and WS rats were
      administered DOCA, enalapril, or furosemide and NaCl appetite was determined.
      Both strains showed comparable NaCl appetite during each of these treatments.
      However, during a 5-week regimen of DOCA with only NaCl-KCl solution to drink,
      uninephrectomized WF rats consumed less than WS rats. Thus, despite reported
      resistance to MC-induced hypertension, neither LE nor WF strains of rats showed
      correspondingly marked deficits in induced NaCl appetite.

PMID- 9661982
TI  - Grooming in Lurcher mutant mice.
AB  - Lurcher mutant mice, characterized by degeneration of cerebellar Purkinje cells
      and granule cells, were compared to normal littermate controls for different
      facets of grooming and nongrooming behaviors after a brief period of water
      immersion. By comparison to normal controls, the number and the duration of
      several grooming components were decreased in Lurcher mutant mice, namely,
      licking the forelimb, the abdomen, the back, and the hindlimb. By contrast, the
      number and duration of body-shaking episodes were not reduced. Lurcher mutants
      had fewer grooming elements for bouts with at least five elements. However, the
      serial organization of grooming, as determined by the order of appearance of
      grooming elements, was maintained in Lurcher mutants. These results indicate that
      the cerebellar cortex is involved in the appearance of various grooming elements
      but not in the organization of the cephalocaudal sequence.

PMID- 9661983
TI  - Prenatal exposure to ethanol disrupts spatial memory: effect of the training
      testing delay period.
AB  - The present study investigated how variations in the period of delay between
      training and testing in the Morris water maze task affect the use of spatial
      memory in adult rats that were prenatally exposed to ethanol. Previous results
      utilizing the Morris water maze task have shown that prenatal, or early
      postnatal, exposure to ethanol produces deficits in the use of spatial memory, a
      type of memory that is dependent on an intact hippocampus. However, in these
      prior studies the delay period between the training of animals and the testing of
      spatial memory is typically fixed at only 1 day. In the current study, which
      utilized a revised training procedure within the Morris water maze task, the
      period of delay between training and testing was altered such that it was either
      1 day or 3 days. Following the 3-day delay, different levels of prenatal exposure
      to ethanol impaired the use of spatial memory. In contrast, following the 1-day
      delay, prenatal exposure to ethanol failed to impair the use of spatial memory.
      The present study thus shows that prenatal exposure to ethanol differentially
      affects spatial memory in the Morris water maze task depending on the period of
      delay between training and testing.

PMID- 9661984
TI  - Effect of intracerebroventricular injection of atropine on metabolic responses
      during exercise in untrained rats.
AB  - To investigate the role of the central cholinergic system in the regulation of
      metabolism during exercise, we injected atropine (5 x 10(-7) mol) into the
      lateral cerebral ventricle of normal and adrenodemedullated (ADM) untrained rats
      submitted to exercise on a treadmill (15 m min(-1), 5% grade) until exhaustion.
      Concentrations of blood glucose, plasma free fatty acids (FFA), and lactate were
      measured before and every 10 min after the start of exercise for a period of 60
      min. Adrenomedullectomy had no effect on the maximal capacity of exercise (MCE),
      but atropine administered intracerebroventricularly (i.c.v.) reduced the maximal
      capacity of exercise of both normal and ADM rats. In normal rats, blood
      concentrations of glucose and plasma free fatty acids remained essentially
      unchanged compared to the levels at rest, whereas in ADM rats a rapid increase in
      plasma glucose and plasma free fatty acids levels occurred during exercise. These
      data indicate that adrenomedullectomy disrupted the accuracy of the feedback
      mechanism that regulates the mobilization of extramuscular fuels during exercise
      in normal rats. In addition, ADM rats showed an increased lipid mobilization as a
      source of energy during exercise, which might explain the increased plasma
      glucose by an inhibition of muscle glucose uptake. These results suggest that
      central cholinergic neurons might be involved in the control of energy substrate
      adjustment during exercise, thereby reducing the maximal capacity of exercise. In
      addition, the results of this study suggest that the adrenal glands are important
      for an accurate feedback mechanism during exercise.

PMID- 9661985
TI  - Learning in year-old female autoimmune BXSB mice.
AB  - BXSB/ MpJ-Yaa and NZB/BINJ mice have been used as animal models for both
      developmental learning disability and systemic autoimmune disease. Approximately
      40-60% of these animals show ectopic clusters of neurons in Layer I of cortex
      similar to those found in postmortem analyses of human dyslexics, and all exhibit
      an autoimmune condition similar to systemic lupus erythematosus (SLE) in humans.
      The expression of immune disease in the BXSB strain, unlike in humans, is more
      severe in males than females. Most previous studies have examined the behavioral
      sequelae of neocortical ectopias at a relatively young age, when the BXSB females
      (unlike the male BXSB and female and male NZBs) are not yet showing high titers
      of autoantibodies associated with their lupus-like form of autoimmune disease.
      This study examined the behavior of BXSB females at an age subsequent to
      autoimmune disease onset. When contrasted with younger animals, year-old BXSB
      females showed good learning behavior, with no differences in Lashley maze
      learning and remarkably good performance in a visual discrimination learning
      task. These results are consistent with other data which indicate that many types
      of learning behavior are apparently unperturbed by systemic autoimmune disease.
      Results also showed significant interactions between a measure of lateral paw
      preference and the presence or absence of ectopias in Lashley maze learning.
      Animals without ectopias that exhibited a right lateral paw preference showed the
      greatest number of errors on a number of test measures. These findings support
      previous results indicating that behavioral effects associated with ectopias may
      vary based upon the behavioral laterality of affected animals.

PMID- 9661986
TI  - Detecting subtle differences in behavior using waveform display analysis.
AB  - We have devised a method, behavioral waveform display analysis, to analyze
      complex ethological information by measuring behavior in real time and
      visualizing it as a time-dependent, multistate waveform. To facilitate the
      generation and statistical analysis of behavioral waveform displays, we have
      designed a simple Macintosh-based software program. When keystrokes coded to
      particular behavioral states are entered in real time, this software measures and
      collates the time, frequency, and duration of each behavioral state. These data
      can then be displayed either in a tabular format for statistical analysis of
      behavioral duration and frequency or as graphical coordinates for creating
      waveform displays by direct importing into graphing programs. An illustration of
      the use of waveform display analysis to detect anomalous behaviors in cocaine-
      and amphetamine-treated mice, some of which are not detectable by a standard time
      sampling assay, is shown. Both waveform display and time-sampling analysis
      detected drug-induced changes in sniffing, bar hanging, digging, and rearing.
      However, unlike time-sampling analysis, waveform display analysis also detected
      changes in the total duration, frequency, and average duration of these behaviors
      as well as additional changes in gnawing and locomotion. Additionally, visual
      scanning of behavioral waveform displays detected drug-induced changes in the
      patterns of behavior not detectable by time-sampling, including 1) a staged
      progression to a limited behavioral repertoire consisting of sniffing,
      locomotion, and rearing; 2) rapid switching between these remaining few
      behaviors; 3) a delayed onset of postinjection rearing relative to sniffing and
      locomotion; and 4) the absence of other transient stereotypies during the onset
      of drug action. These data indicate that behavioral waveform display provides an
      approach for the detection, visualization, and statistical analysis of aspects of
      complex behavior not amenable to detection by time-sampling methods.

PMID- 9661987
TI  - A comparison of feeding to cephalic stimulation on postprandial sleepiness.
AB  - This study investigated the effects of ingestion of a meal compared to a sham
      feeding on objectively measured sleepiness. It was hypothesized that the
      ingestion of a solid meal would produce significantly greater postprandial
      sleepiness evidenced by shorter sleep onset latencies (SOL) when compared to a
      sham feeding. Eleven men and eight women without evidence of gastrointestinal
      disease or sleep disorders participated in the 2-day study. Subjects underwent a
      premeal baseline nap at 1600 hours and were given a standardized meal at 1700
      hours. On one study day, subjects consumed the entire meal, whereas on another
      study day, they were asked to chew and then expectorate the meal. Naps with
      polysomnographic monitoring followed at 1730, 1800, and 1900 hours. Sleep onset
      latencies were determined by standard polysomnographic measures. Statistical
      analyses revealed the sleep onset latencies for the two meal conditions differed
      significantly at the 1800 hours postprandial nap only. Individuals demonstrated a
      transient decrease in sleep latency after consuming a meal compared to a sham
      feeding. These results lend support to the existence of a gastrointestinal effect
      on postprandial sleepiness.

PMID- 9661988
TI  - Provisional quantitative trait loci (QTL) for the Aschoff effect in RI mice.
AB  - Mice of the CXB recombinant inbred (RI) panel were phenotyped for period of
      locomotor activity in continuous dark (tau) and in continuous 10-lux light
      (tauLL). There were significant differences in the effect of light on period,
      delta tau (tauLL-tau), among CXB RI strains and their progenitors. By comparing
      strain means for delta tau in the CXB RI strains with typed genetic loci using a
      product moment correlation, it was possible to hypothesize quantitative trait
      loci (QTL) important to the genetic variance in the effect of constant low-level
      light on circadian period. Some of the candidate genes linked to statistically
      associated markers are neuropharmacologically interesting. Provisional QTL for
      delta tau were found on proximal Chromosome 8 and mid Chromosome 11 in regions
      near QTL identified in a similar analysis of the BXD RI panel. This provides
      additional evidence for the importance of loci on Chromosomes 8 and 11.

PMID- 9661989
TI  - Interaction of stress, smoking, and dietary restraint in women.
AB  - Smoking cessation often results in weight gain but certain subtypes of smokers
      may be more likely than others to gain weight. Women high in dietary restraint
      ("restrainers") increase food intake and gain more weight than nonrestrainers
      during smoking cessation. Restrainers have also been reported to increase food
      intake following laboratory stressors. Therefore, the present study was designed
      to measure the influence of stress on food intake and subjective distress during
      acute smoking abstinence in restrained and nonrestrained women. Participants were
      48 women, 18-40 years old, comprising six groups (n = 8 per group) in a 2 x 3 x 2
      design. Groups consisted of two levels of restraint (restrained and
      nonrestrained) and three levels of smoking (ad lib. smokers, abstinent smokers,
      and nonsmokers), whereas the within-participant manipulation involved two
      sessions differing in stress (stress and control). Snack foods were available for
      consumption. Results showed that distress, measured by the Stress-Arousal
      Checklist and visual analogue measures of tension and anxiety, was higher in the
      stress session for all groups except for restrainers who smoked ad lib.
      Furthermore, distress was significantly higher in smoke-abstinent restrainers
      during the stress session than all other conditions. However, despite differences
      in distress, no effect was observed for food intake. Desire for a cigarette
      showed a sharper increase over the stress session for restrainers compared with
      nonrestrainers but did not differ in the control session. These data suggest that
      restrainers may use smoking to reduce distress and may increase smoking, but not
      eating, during stress.

PMID- 9661990
TI  - Involvement of the anterodorsal thalami nuclei on the hypophysoadrenal response
      to chronic stress in rats.
AB  - Anterodorsal thalami nuclei (ADTN) exert an inhibitory influence on the
      hypophysoadrenal system (HAS) under basal and acute stress conditions; however,
      after chronic stress, the effect is different. The response to chronic
      immobilization stress (IMO) (forced immobilization for 15 min/day for 12 days)
      and variable chronic stress (V) (24-day exposure to different stressors per day)
      of plasma ACTH and corticosterone (C) in rats with anterodorsal thalami nuclei
      lesions was studied. In sham-lesioned rats, chronic immobilization stress and
      variable chronic stress induced a significant increase in plasma ACTH and C and a
      reduction of adrenal C content. After exposure of lesioned rats to chronic
      immobilization stress, there was a decrease of plasma ACTH compared to that in
      unstressed lesioned rats. In contrast, there was significant increase in ACTH
      levels after variable chronic stress, this increase being smaller than the
      variable increase elicited in sham-lesioned rats. In all stressed lesioned
      animals, plasma C remained unchanged. However, adrenal C content decreased
      significantly compared to that in unstressed lesioned rats. These findings
      demonstrate that anterodorsal thalami nuclei lesions attenuated the
      hypophysoadrenal system response to chronic stress. These data are in contrast to
      those obtained in previous studies under basal and acute stress conditions. The
      reason for this discrepancy is at present unknown, and its elucidation will
      require further studies.

PMID- 9661991
TI  - Ethanol's effects on operant responding: differentiating reinforcement efficacy
      and motor performance.
AB  - The purpose of this study was to examine the effects of ethanol on operant
      responding in rats. Drugs may affect response rates by several mechanisms,
      including altering motor performance or sensitivity to reinforcement. These two
      processes can be dissociated by applying a quantitative model of reinforced
      responding the response-strength equation, to response rates obtained during
      multiple variable-interval (VI) schedules of reinforcement. This equation has two
      fitted parameters. One (k) is thought to measure changes in motor performance,
      and the other (Re) is thought to measure changes in reinforcement efficacy. In
      experimental sessions, rats earned sucrose reinforcement on a seven-component
      multiple VI operant schedule. The average intervals varied from 108 to 3 s and
      provided reinforcement rates from 30 to 1200/h. Following stable baseline
      performance, rats were injected intraperitoneally prior to sessions with
      different doses of ethanol: 0.0, 0.3, 0.6. and 0.9 g/kg. Low to moderate doses of
      ethanol (0.3 and 0.6 g/kg) significantly decreased response rates on several of
      the VI schedules but did not alter either of the fitted parameters, suggesting
      that these doses of ethanol did not affect motor performance or sensitivity to
      reinforcement. The 0.9 g/kg dose decreased responding maintained by many of the
      VI schedules and significantly increased the Re parameter, suggesting that the
      sucrose became relatively less efficacious in ethanol compared to vehicle
      sessions. This relatively high dose of ethanol, however, did not alter responding
      maintained by the richest reinforcement schedule, and it did not affect motor
      performance as defined by the k parameter. These results suggest that, within
      this paradigm, ethanol affects motivation to respond rather than ability to
      respond.

PMID- 9661992
TI  - Evolution in the conceptualization of dementia and Alzheimer's disease: Greco
      Roman period to the 1960s.
AB  - Most histories of senile dementia commence with Alois Alzheimer's description in
      1906 of the first case of Alzheimer's disease, yet the history of senile dementia
      before 1906 is quite rich, dating back to the ancient Greek and Roman
      philosophers and physicians. Over the 2500 years since ancient times, the concept
      of senile dementia has evolved from a rather vague notion that mental decline
      occurred inevitably in old age, to become defined today by a distinct set of
      clinical and pathological features with the potential for treatment and
      prevention within grasp. Throughout history, many elderly individuals with
      unpredictable behavior were sequestered in institutions, and the line between
      mental disorders and senile dementia was hazy at best. The identification of
      Alzheimer's disease at the onset of the 20th century was a turning point for the
      understanding of senile dementia, and the concepts and histological findings
      presented by the early researchers of Alzheimer's disease remain relevant still
      today. Indeed, these early findings are proving to be a continuing source of
      insight, as many of the issues debated at the turn of the century remain
      unresolved still today. This paper thus traces the history of the evolution of
      our current conceptualization of Alzheimer's disease from the amorphous Greco
      Roman concept of age-associated dementia.

PMID- 9661993
TI  - Increased natural killer cell cytotoxicity in Alzheimer's disease may involve
      protein kinase C dysregulation.
AB  - Increased cytokine-mediated cytotoxic natural killer (NK) cell activity has
      recently been demonstrated in patients with senile dementia of the Alzheimer's
      type (SDAT). In the present study, we evaluated whether protein-kinase C (PKC), a
      main regulatory enzyme involved in the mechanism of exocytosis by NK cells, has a
      role in the cytotoxic response of NK cells (during IL-2 and IFN-beta exposure)
      from SDAT patients. Our data demonstrate the presence of an increased cytotoxic
      response by NK cells to IL-2 (mean increase +102%) and IFN-beta (mean increase
      +132%) in SDAT patients in comparison with healthy elderly subjects (+75% and
      +88% for IL-2 and IFN-beta, respectively). A smaller suppression of NK
      cytotoxicity after cortisol was also observed in SDAT (mean decrease -24%) than
      in the control group (-44%). The NK cell activity of SDAT patients was inversely
      correlated with the cognitive status as evaluated by the analysis of MMSE (Mini
      Mental State Examination) score. A comparison of young and elderly healthy
      subjects revealed no variations in NK cell activity. A physiological decrease in
      cytosolic PKC activity was demonstrated in healthy old subjects after IL-2 and
      IFN-beta incubation, but not in SDAT patients, while no variations in kinase
      activity were observed after cortisol incubation. The decreased activity with
      cytokines was associated with reduced levels of PKC alpha and betaII isoforms. An
      alteration in cytokine-mediated NK cell activity associated with PKC
      dysregulation is therefore suggested to occur in patients with SDAT. These
      changes may indicate the existence of an immunological component to the
      pathogenesis and progression of the disease.

PMID- 9661994
TI  - Indomethacin reverses the microglial response to amyloid beta-protein.
AB  - Alzheimer's disease (AD) brains display intense microglial immunoreactivity in
      the area of senile plaques, suggesting that amyloid beta-protein may stimulate
      microglial infiltration. The activated microglia may modulate an immune response
      in the brain. Non-steroidal anti-inflammatory drugs (NSAIDs) are candidate
      therapeutics for AD because their effects on immune system components may
      influence the course of the disease. The present study examined the effects of an
      NSAID (indomethacin) on amyloid beta-protein-induced microglial infiltration.
      Amyloid beta-protein was chronically infused into rat lateral ventricles for 2
      weeks. Extracellular amyloid beta-protein deposited along the lining and diffused
      into the tissue surrounding the lateral ventricle. Immunocytochemical staining
      showed that animals receiving amyloid beta-protein exhibited dramatic microglial
      response when compared to vehicle-infused rats. Activated microglia surrounded
      immunopositive amyloid beta-protein deposits, but this response was significantly
      attenuated in animals receiving either concurrent i.c.v. or subcutaneous (s.c.)
      treatment with indomethacin. These results suggest that chronic amyloid beta
      protein infusion induces the proliferation of activated microglia and that
      indomethacin may be an effective treatment for inhibiting microglial
      proliferation.

PMID- 9661995
TI  - Autoantibodies in neurodegenerative diseases: antigen-specific frequencies and
      intrathecal analysis.
AB  - The frequency of autoantibodies (AAbs) was surveyed in several neurodegenerative
      diseases, other neurological diseases, and controls using antigen-specific EIAs
      for neurofilament heavy subunit, tubulin, glial fibrillary acidic protein, S100
      protein, tau, beta-amyloid peptide, myelin basic protein, and heparan sulfate
      proteoglycan. High frequencies of sera and cerebrospinal fluid tubulin AAbs were
      found in Alzheimer disease (62% and 69%, respectively), Parkinson disease (27%
      and 70%), amyotrophic lateral sclerosis (54% and 67%), and in sera from multiple
      sclerosis (50% and 67%), optic neuritis (85%), Guillain-Barre syndrome (88%), and
      vascular dementia (52%). High frequencies of neurofilament heavy subunit AAbs
      were detected in Guillain-Barre syndrome, chronic peripheral neuropathy (88%) and
      optic neuritis (62%); whereas, some Alzheimer's disease (33%) and vascular
      dementia (44%) patients had glial fibrillary acidic protein AAbs. Lower
      frequencies of other AAbs were found in patient groups. AAb results were also
      compared to functional assessment of blood-brain barrier integrity in Parkinson's
      disease and Alzheimer's disease. The relevance of these AAbs to pathogenesis
      and/or course of neurologic diseases merits further study with particular
      reference to subgrouping and prognosis.

PMID- 9661996
TI  - Evaluation of muscarinic M2 receptor sites in basal forebrain and brainstem
      cholinergic systems of behaviorally characterized young and aged Long-Evans rats.
AB  - Aged (23-25-month-old) male Long-Evans rats were assessed for deficits in spatial
      cognition relative to young (4-6-month-old) rats. An in vitro autoradiography
      study was then conducted for muscarinic M2 sites using [3H]AF-DX 384 to assess
      binding in basal forebrain and brainstem areas where cholinergic neurons are
      localized. The analysis of basal forebrain included the medial septal/diagonal
      band region that provides cholinergic innervation of the hippocampus; the
      laterodorsal tegmental nucleus and pedunculopontine tegmental nucleus were
      analyzed in the brainstem. A significant age-related reduction in M2 binding was
      found in both the basal forebrain and brainstem. Only the reduction in the basal
      forebrain, however, was correlated with spatial learning impairment. Although the
      basal forebrain and brainstem cholinergic systems are each vulnerable in normal
      aging, contributions to the behavioral effects of aging may be distinctive for
      the two systems.

PMID- 9661997
TI  - Effects of age on pilocarpine-induced c-fos expression in rat hippocampus and
      cortex.
AB  - The effect of age on pilocarpine-induced expression of the immediate-early gene c
      fos was examined in the hippocampus and cortex of Long-Evans rats. Rats were
      treated with either pilocarpine (25 mg/kg) or saline, and sacrificed 90 min.
      following injection. The level of c-fos mRNA and Fos-like protein expression was
      determined using in situ hybridization histochemistry, and immunocytochemistry,
      respectively. In saline-treated animals, comparable levels of c-fos mRNA and Fos
      like protein were observed in the hippocampus and cortical regions of young (6
      month) and aged (24-26 months) rats. The expression of Fos-like protein following
      pilocarpine treatment was increased, however, in frontal, retrosplenial, and
      cingulate cortex of aged compared to young rats. In frontal and retrosplenial
      cortex, the changes in Fos-like protein were accompanied by changes in c-fos mRNA
      expression. In contrast, no age difference was detected in the hippocampus or
      parietal cortex of pilocarpine-treated rats. These regionally-specific age
      differences in response to pilocarpine administration suggest that mechanisms
      localized to those areas play an important role in determining the response to
      cholinergic stimulation mediated through post-synaptic muscarinic receptors.

PMID- 9661998
TI  - Glucose treatment attenuates spatial learning and memory deficits of aged rats on
      tests of hippocampal function.
AB  - Groups of old and young rats were administered three tests of spatial learning
      and memory that are known to be sensitive to hippocampal dysfunction: the radial
      arm maze (RAM), spatial non-matching-to-sample (SNMTS), and a spatial vs. local
      cue-preference task. Old rats performed worse than young rats on the RAM and
      SNMTS tasks; on the cue-preference task, young rats were biased to use spatial
      cues, whereas old rats exhibited strong preferences for distinct, local cues.
      Peripheral injections of glucose (100 mg/kg) improved performance by old rats on
      the RAM and SNMTS, which correlated with measures of glucose metabolism. Glucose
      treatment did not affect old rats performance on the cue-preference task. There
      was evidence that glucose-treatment improved performance of young rats in the RAM
      test, but not the other tests. The results extend the range of tasks on which
      glucose-induced cognitive enhancement has been demonstrated in aged rats, and
      provides further evidence that memory loss resulting from hippocampal dysfunction
      is especially amenable to glucose treatment.

PMID- 9661999
TI  - Aging effects on the startle response and startle plasticity in Fischer F344
      rats.
AB  - The effects of aging on acoustic and airpuff startle reactivity, acoustic and
      airpuff startle habituation, acoustic and cross-modal (light-acoustic) prepulse
      inhibition (PPI), and fear-potentiated startle (FPS) were examined using 3- (Y:
      young), 11- (AD: adult), 17- (MA: middle-aged), and 22- (O: old) month-old
      Fischer F344 rats. AD rats had the highest acoustic startle reactivity with the Y
      and MA rats showing smaller and comparable startle levels. The O rats had
      diminished startle reactivity, with over a 65% reduction in responding. Airpuff
      startle reactivity was comparable in the Y and AD groups, while the MA and O
      groups had 40% and 80% reductions in airpuff startle respectively. There was an
      age-related increase in airpuff startle habituation. Acoustic and cross-modal PPI
      were reduced significantly in O rats when compared to other age groups. Finally,
      there were no effects of age on FPS. In summary, these studies suggest that in
      Fischer F344 rats, there are age-associated differences in startle reactivity,
      startle habituation, and PPI, but no aging effect on FPS.

PMID- 9662000
TI  - Calretinin and calbindin-D28K in male rats during postnatal development.
AB  - Calcium-binding proteins play potentially important roles in neurogenesis and
      neuroprotective mechanism(s). Some evidence exists that brain calbindin-D28K
      (CALB) is regulated by androgens. In the present study, calretinin (CALRET) and
      CALB patterns were determined by Western analysis in the medial basal
      hypothalamus (MBH) from male rats along with assaying plasma testosterone levels
      during postnatal development. Testosterone levels were very low in 7-, 10-, and
      30-day-old animals (approximately 0.5 ng/mL), increased in a stair-step fashion
      to peak levels at 90 days (approximately 3.8 ng/mL), then declined with
      increasing age to very low levels at 300 days of age (approximately 0.3 ng/mL).
      At 7 and 10 days, MBH CALRET and CALB levels were low; however, at Day 30 a
      significant twofold increased was observed. Thereafter, in 60-, 120-, 180-, and
      300-day-old animals MBH CALRET and CALB levels were, in general, comparable to 30
      day-old values. These findings suggest that there is not a clear correspondence
      between the androgen status in male rats and the calcium-binding proteins (CALRET
      & CALB) expressed in the MBH. Therefore, it appears that brain CALRET and CALB
      are regulated in a developmental fashion with significant increases in expression
      occurring around the 4th postnatal week.

PMID- 9662001
TI  - Age-related changes in [3H]MK-801 binding in the Fischer 344 rat brain.
AB  - In this study we tested the hypothesis that the efficacy of L-glutamate to
      stimulate [3H]MK-801 binding to the NMDA receptor/channel complex is altered as a
      function of aging. L-Glutamate, or related excitatory amino acid (EAA), is the
      endogenous neurotransmitter of the NMDA receptor/channel complex. These studies
      examined the efficacy and potency with which L-glutamate produces receptor
      activation, channel opening and subsequent MK-801 binding as a function of
      increasing age by comparing dose-response curves (EC50 and Emax) from 6-, 12-,
      and 24-month-old F-344 rats. The number of NMDA receptors, as determined by
      [3H]MK-801 binding in the presence of a saturating concentration of L-glutamate,
      was reduced in the inner frontal cortex, entorhinal cortex and the lateral
      striatum in aged rats when compared with young adults. When a range of L
      glutamate concentrations were used, differences in Emax were noted in the same
      brain regions in addition to several others in aged and middle-aged animals when
      compared with young-adult animals. No changes in EC50 values were noted in any of
      the brain regions at either age when compared with young-adults.

PMID- 9662002
TI  - Brain weight does not decrease with age in adult rhesus monkeys.
AB  - Cross-sectional studies on adult human autopsy material have shown that younger
      cohorts have heavier brains than older groups. We sought to determine whether a
      similar pattern is present in the rhesus monkey, a species that serves as a
      useful model of human brain and cognitive aging. Data were obtained from
      necropsies of 399 rhesus monkeys (180 females; 219 males), of ages covering the
      entire adult lifespan of this species. In addition to fresh brain weight,
      variables considered were age, sex, body weight, heart weight, identity of the
      prosector, and circumstance of death. Initial bivariate analyses revealed a
      significant sex difference in brain weight (mean for males: 96.1 g; for females:
      86.1 g; p < 0.001), as well as significant correlations of brain weight with body
      weight (r = 0.20, p < 0.01 for females; r = 0.27, p < 0.001 for males), and heart
      weight (r = 0.27, p < 0.001 for females; r = 0.38, p < 0.001 for males). Identity
      of prosector, circumstance of death, and age were not significantly related to
      brain weight in bivariate analyses. Multiple linear regression, controlling for
      possible confounding effects of body weight and sex, also suggested that brain
      weight is stable throughout adulthood in the rhesus monkey.

PMID- 9662003
TI  - Long-term food restriction, deprenyl, and nimodipine treatment on life expectancy
      and blood pressure of stroke-prone rats.
AB  - We determined whether food restriction or the drugs nimodipine (Ca2+ antagonist)
      and deprenyl (a MAO-B inhibitor) prevent the development of stroke in the
      spontaneously hypertensive stroke-prone rat (SHR-SP). Forty male SHR-SP rats, in
      the age of 34 weeks, were exposed to various treatments. During a period of 27
      weeks, survival and blood pressure were followed. In the control and deprenyl
      group, the blood pressure values remained unchanged; 50% had died after 27 weeks.
      All rats that were treated with nimodipine survived. After food restriction, 7/8
      rats survived and showed a lower blood pressure. This study in SHR-PR rats shows
      the superiority of nimodipine on survival, and the potential of food restriction
      as a stroke-preventing measure.

PMID- 9662005
TI  - Advancing oral and maxillofacial surgery in the developing world.

PMID- 9662006
TI  - Unusual conditions of the major and minor salivary glands.

PMID- 9662004
TI  - Hippocampal age differences reoccur after modification of stimulus configurations
      in rabbit jaw movement conditioning.
AB  - Rabbits of two age groups, young (3-7 months; n = 7) and aging (40-49 months; n =
      7), were implanted with chronic recording electrodes in area CA1 of dorsal
      hippocampus and trained in a delay conditioned jaw movement (CJM) paradigm (after
      previously reaching criterion in a trace CJM paradigm with the same conditioned
      stimulus and unconditioned stimulus). Unlike results from the trace experiment,
      there was no significant difference in trials to behavioral criterion between the
      two age groups. There were large, but temporary, differences in the magnitude of
      conditioning-related hippocampal neural responses early in delay training. Aging
      rabbits' hippocampal responses were significantly smaller on Day 2 of delay
      training than corresponding responses of young rabbits (p = 0.0008). It is
      important to note that neural differences were not observed on Days 1 and 3 of
      delay training or at criterion performance in the prior trace conditioning. These
      results are interpreted in terms of age-related differences in hippocampal
      responsiveness to changes in biologically significant stimulus configurations.

PMID- 9662008
TI  - Modified technique in surgical correction of macrostomia.
AB  - A technique is presented to correct macrostomia with a simple straight line
      incision and incorporation of a small triangular flap to achieve proper
      positioning of the commissure with minimal visible scar.

PMID- 9662007
TI  - The natural course of nonreducing disk displacement of the temporomandibular
      joint: changes in condylar mobility and radiographic alterations at one-year
      follow up.
AB  - Changes in condylar mobility and radiographic changes were examined in 22
      patients (26 joints) who had nonreducing disk displacement. The patients had no
      treatment for at least one year. Thirty joints in 15 persons with no current or
      previous temporomandibular joint symptoms served as a control. The clinical signs
      and symptoms tended to be less severe after one year. Condylar mobility increased
      significantly during this period, although it remained somewhat limited. There
      was no significant difference in frequency of radiographically discernible
      changes of the condyle between patients and controls and the patients showed
      minimal evidence of progressive disease.

PMID- 9662009
TI  - Autotransplantation of premolars. A retrospective study.
AB  - The purpose of this clinical follow-up study was to evaluate the success rate of
      autotransplantation of human premolars. In the period between 1982 and 1994, 46
      premolars in 31 patients were transplanted. A long-term success rate of 97.5%
      with a mean follow-up period of 3.5 years was achieved. It seems to be justified,
      therefore, in selected cases, to consider the possibility of autotransplantation
      as a good alternative to orthodontic or prosthetic treatment, including implant
      insertion, when closing a gap in the dental arch.

PMID- 9662010
TI  - Pathological fractures of the mandible. A review of the etiology and treatment.
AB  - A retrospective study was undertaken to analyse the etiology, site and treatment
      procedures of 30 pathological fractures of the mandible. Fifty percent of the
      fractures had an inflammatory cause. The remaining cases were associated with
      severe atrophy of edentulous mandibles (4), benign tumours (3), cysts (3), and
      primary or secondary malignancies (5). Regardless of the cause, the majority of
      the fractures occurred in the body of the mandible. Pathological fractures of the
      mandible most often have to be treated by eliminating the cause of the underlying
      condition while immobilizing the fragments either with osteosynthesis or archbars
      and intermaxillary fixation.

PMID- 9662011
TI  - Surgical reduction and fixation of intracapsular condylar fractures. A follow up
      study.
AB  - Controversies still exist about the preferred treatment of condylar head and neck
      fractures. Newly developed access techniques in combination with new methods to
      fix the fragments, lead to satisfactory results. This study deals with a
      refinement of surgical treatment of intracapsular fractures.

PMID- 9662012
TI  - Ocular psychiatric disorders in maxillofacial injuries. Two case reports and a
      review of psychogenic ocular symptoms.
AB  - Ocular signs and symptoms associated with facial trauma can be a manifestation of
      an underlying psychiatric disorder which may exist prior to the traumatic
      incident, or even develop as a result of the stressful traumatic experience in a
      psychologically vulnerable individual. Two such cases are presented. A brief
      review of psychogenic ocular symptoms as well as suggestions for evaluation and
      treatment are discussed.

PMID- 9662013
TI  - Etiology of cancer of the lip. A review.
AB  - A range of environmental and host factors has been identified to explain the
      etiopathogenesis of squamous cell carcinoma of the lip. However, the definitive
      pathogenic pathway remains unclear. Carcinogenesis does not seem to be limited to
      a single agent, but rather to a complex multistep process of interactions between
      putative risk factors. In this paper, the currently available data regarding risk
      factors, considered to be causally related to the onset of lip cancer, are
      reviewed.

PMID- 9662014
TI  - The anti-tumor effect of photodynamic therapy evaluated by bromodeoxyuridine
      immunohistochemistry.
AB  - The anti-tumor effect of photodynamic therapy (PDT) on mouse tumors was evaluated
      with bromodeoxyuridine (BrdU) immunohistochemistry. BrdU was injected into the
      mice intraperitoneally (40 mg/kg body weight). Immediately after injection of
      BrdU, PDT using a photosensitizing drug (hematoporphyrin oligomers: 20 mg/kg body
      weight) was carried out on the experimental group but not on the control group.
      BrdU labeling indices (LIs) of the tumor cells close to blood vessels and
      adjacent to the surrounding normal tissue were investigated. In the tumor cells
      close to blood vessels, the LIs of the experimental group were significantly
      lower than those of the control group. As for the tumor cells adjacent to the
      surrounding normal tissue, the LIs of the experimental group were similar to
      those of the control group. Thus, the effect of PDT was significant in the tumor
      cells close to the blood vessels, while the tumor cells adjacent to the
      surrounding normal tissue resisted PDT.

PMID- 9662015
TI  - Immunohistochemical analysis of the oncoprotein c-erbB-2 expression in oral
      benign and malignant lesions.
AB  - Thirty-seven samples of oral mucosa were analysed and divided histologically into
      groups of normal mucosa (6), hyperplastic lesions (6), dysplastic lesions (14),
      and squamous cell carcinoma (11). All lesions displayed some expression of c-erbB
      2 but the distribution and intensity of expression varied strongly according to
      the differentiation. The lower the epithelial differentiation of the sample, the
      higher the expression of c-erbB-2 oncoprotein showing very strong staining in
      carcinoma samples. This suggests that in oral carcinoma, transformation might be
      related to c-erbB-2 interaction.

PMID- 9662016
TI  - Merkel cell carcinoma in a patient with Recklinghausen neurofibromatosis.
AB  - A rare case is described of Merkel cell carcinoma of the cheek arising in a
      cutaneous neurofibroma in a patient with Recklinghausen neurofibromatosis. The
      relevant literature is reviewed.

PMID- 9662017
TI  - Parosteal chondrosarcoma attached to the hyoid bone. A case report.
AB  - A parosteal chondrosarcoma with low-grade malignancy attached to the hyoid bone
      in a 66-year-old man is reported. The tumor was considered to present a low-grade
      malignancy because slight invasion into the surrounding soft tissues and rapid
      growth were observed. Four years after initial surgery he had a local recurrence.
      To the best of our knowledge, this is the first reported case of parosteal
      chondrosarcoma in this location.

PMID- 9662018
TI  - Flow cytometric analysis of cell cycle fractions in oral leukoplakia.
AB  - Flow cytometric analysis of cell cycle fractions and DNA ploidy was performed on
      39 biopsy specimens of oral leukoplakia. The aneuploidy rate of these
      leukoplakias was 9/39 (23.1%) and the mean DNA index of the aneuploid lesions was
      1.34. The aneuploidy rate was significantly higher in severely dysplastic lesions
      (8/17) than in mildly dysplastic (1/15, P<0.02) and nondysplastic (0/7, P<0.05)
      lesions. No significant differences in the percentages of each cell cycle
      fraction were seen between the diploid and the aneuploid leukoplakias. However,
      the S-phase fraction of the severely dysplastic lesions (23.0%) among the diploid
      leukoplakias was higher than those of the mildly dysplastic (12.4%) and
      nondysplastic (15.5%) lesions, and the difference between the severely dysplastic
      and the mildly dysplastic lesions was statistically significant (P<0.001). These
      results suggest that flow cytometric analysis of cell cycle fractions and DNA
      ploidy might offer additional information for assessing the malignant potential
      of oral leukoplakias.

PMID- 9662019
TI  - Osteoma of the mandibular coronoid process. Report of a case.
AB  - A case of osteoma of the coronoid process in a 51-year-old woman is presented.
      Surgical resection, followed by postoperative physiotherapy to stimulate normal
      function, is the treatment of choice for this lesion.

PMID- 9662020
TI  - Unusual elimination of a salivary calculus. A case report.
AB  - Salivary calculi are frequently formed in the submandibular duct. The most common
      sites are where the duct turns round the distal edge of the mylohyoid, where the
      duct crosses the lingual nerve, and just distal to the duct orifice. Untreated
      calculi can cause obstruction and glandular atrophy, and then may exfoliate
      through the floor of the mouth. An unusual case of cutaneous exfoliation of a
      salivary gland stone is presented. The importance of early diagnosis and
      treatment of sialolithiasis are discussed.

PMID- 9662021
TI  - Beta-2-microglobulin-associated nodular amyloidosis of the tongue.
AB  - The tongue is an uncommon site for the deposition of beta-2-microglobulin
      amyloid. A case is presented of nodular amyloidosis of the tongue in a patient
      having prolonged hemodialysis. The lesions were small, firm, yellowish nodules on
      the lateral aspect of the tongue and were shown to be deposits of beta-2
      microglobulin amyloid. The pathogenesis and differential diagnosis are discussed.

PMID- 9662022
TI  - Stability assessments and histology of titanium implants placed simultaneously
      with autogenous onlay bone in the rabbit tibia.
AB  - A disc-shaped bone graft was harvested from the calvarium in ten rabbits and
      anchored as an onlay bone graft, using a titanium implant, at the proximal tibial
      metaphysis. The contralateral tibia served as the control, where an implant was
      placed without a graft with the implant head at a height corresponding to the
      thickness of the graft on the test side. Resonance frequency measurements were
      performed 4, 8, 16 and 24 weeks postoperatively and removal torque measurements
      were performed at 24 weeks. A statistically significant higher implant stability,
      as assessed by resonance frequency measurements (RFM), was measured from 4 weeks
      throughout the 24-week period. The mean peak removal torque for the test implants
      was 50.4+/-10.0 Ncm and 30.0+/-6.9 Ncm for the control implants, which was a
      statistically significant difference. Histologically, the grafted bone was well
      incorporated and morphometry revealed more bone around the test implants.
      Calculations of shear stresses indicated that the grafted bone had similar
      biomechanical properties to the cortical bone of the recipient site. It is
      concluded that the integration of titanium implants in autogenous onlay bone
      grafts results in an increased biomechanical support of the implant. The use of
      RFM may also serve as a useful instrument for noninvasive monitoring of implant
      stability in vivo.

PMID- 9662023
TI  - Molecular architecture of the trypanosome cytoskeleton.

PMID- 9662024
TI  - The role of proteolysis during differentiation of Trypanosoma brucei from the
      bloodstream to the procyclic form.
AB  - The in vitro differentiation of Trypanosoma brucei from bloodstream to procyclic
      (insect) forms is accompanied by diminishing variant surface glycoprotein (VSG)
      and increasing levels of procyclin and phosphoenolpyruvate carboxykinase (PEPCK).
      In this study, we examined the fate of several glycolytic enzymes of T. brucei
      during differentiation. We observed a down-regulation of glycosomal
      phosphoglycerate kinase (gPGK) during differentiation. In contrast, intracellular
      levels of glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH), aldolase
      (ALD), and phosphoglucoisomerase (PGI) remained unchanged during differentiation
      and apparently continued to be synthesized in the procyclic form. To determine
      the potential role of proteasomes and other proteases during the differentiation
      process, we tested the effect of lactacystin, a specific inhibitor of proteasome
      activity, and morpholinourea-Phe-homoPhe-benz-alpha-pyrone (P27), a selective
      inhibitor of cysteine proteases, on the in vitro differentiation of T. brucei.
      Cells differentiated normally in the presence of 1 microM lactacystin, which
      confirmed our previous observation that this differentiation does not require
      crossing any phase boundaries in the cell cycle (Mutomba and Wang, Mol Biochem
      Parasitol 1996;80:89-102). But the cells thus differentiated did not increase in
      number and retained gPGK. Cells differentiated under 2 microM P27 also proceeded
      at a normal rate but failed to multiply and retained gPGK. However, most of the
      differentiated cells under 2 microM P27 also retained VSG on the cell membrane
      surface and expressed higher levels of procyclin suggesting that a cysteine
      protease(s) may be involved in releasing VSG and partially reducing procyclin
      during differentiation. This cysteine protease(s) has been tentatively identified
      in the procyclic cells as a 48 kDa protein through labeling of cysteine
      protease(s) with a biotinylated P27 homolog K02 (morpholinourea-Phe-homoPhe
      vinylsulfone).

PMID- 9662025
TI  - A2rel: a constitutively expressed Leishmania gene linked to an amastigote-stage
      specific gene.
AB  - The A2-A2rel gene copies are arranged in tandem arrays on a 850 kb chromosome in
      Leishmania donovani. Contrary to A2 mRNA which displays amastigote-stage-specific
      expression, A2rel gene expression is constitutive throughout the L. donovani life
      cycle. The A2rel sequence was found to be conserved in all Leishmania species
      tested, while the A2 sequence is specific to L. donovani and L. mexicana. The
      A2rel full length cDNA is of 2.3 kb and it contains one open reading frame coding
      for a putative protein of 436 amino acids.

PMID- 9662026
TI  - Differentially expressed Leishmania major gp63 genes encode cell surface
      leishmanolysin with distinct signals for glycosylphosphatidylinositol attachment.
AB  - The Leishmania cell surface metalloproteinase, leishmanolysin or GP63, is
      expressed in all stages of Leishmania major. Initial studies reported that in L.
      major the gp63 genes were arranged as five homologous, tandemly repeated genes
      (gp63 genes 1-5) and a sixth, less conserved gp63 gene located 8 kb downstream of
      gp63 gene 5. This study compared the sequences of L. major gp63 gene 1 and gp63
      gene 6 and identified a seventh L. major gp63 gene located downstream from gp63
      gene 6. The L. major gp63 genes exhibited stage-specific differences in their
      expression: gp63 genes 1-5 were expressed in promastigotes only, gp63 gene 6 was
      expressed in promastigotes and amastigotes, while gp63 gene 7 was expressed
      predominantly in stationary phase promastigotes and in amastigotes. Analysis of
      the predicted protein sequence of gp63 gene 6 (GP63-6) and gp63 gene 1 (GP63-1)
      showed that these two proteins were homologous in terms of overall predicted
      domain structure. L. major GP63-1 has been reported to contain a
      glycosylphosphatidylinositol (GPI) membrane anchor while sequence analysis
      predicted that GP63-6 contained a different hydrophobic C-terminus that may act
      as a transmembrane region. Transfection studies using L. major gp63 gene 1 and
      gp63 gene 6 expressed in L. donovani promastigotes showed that GP63-6 was
      expressed at the cell surface and that the distinct GP63-6 C-terminus was capable
      of mediating GPI anchor attachment.

PMID- 9662027
TI  - The complete sequence of Plasmodium berghei merozoite surface protein-1 and its
      inter- and intra-species variability.
AB  - The complete gene for merozoite surface protein-1 (MSP-1) from Plasmodium berghei
      has been cloned and sequenced. Comparison of the P. berghei MSP-1 sequence with
      MSP-1 from other rodent parasites reveals five conserved domains interrupted by
      four variable blocks. These variable blocks exhibit no sequence homology but do
      have similar amino acid compositions. Primary proteolytic processing sites are
      located near the boundaries between the conserved domains and the variable
      blocks. Sequencing of the variable blocks from several P. berghei isolates shows
      that the predominant intra-species difference is in the number of tandem repeats.
      The inter- and intra-species differences suggest that the variable blocks are
      localized areas with relatively high levels of slipped-strand mispairing, unequal
      crossing-over, or other intragenic recombination activity. MSP-1 from P. berghei
      exhibits more repetitiveness than MSP-1 from other species suggesting that P.
      berghei experiences a higher intrinsic level of events producing variable numbers
      of tandem repeats or a lower level of events leading to the degeneration of
      tandem repeats.

PMID- 9662028
TI  - A chloroquine resistance locus in the rodent malaria parasite Plasmodium
      chabaudi.
AB  - We have located a possible chloroquine resistance locus in the genome of the
      rodent malaria parasite Plasmodium chabaudi. Two genetically distinct clones of
      the parasite were grown in vivo and allowed to undergo genetic crossing. The
      clones differed from each other in their susceptibility to chloroquine; AS(3CQ)
      had been selected for a low level of resistance to the drug whereas AJ is
      chloroquine-sensitive. Independent recombinant progeny (20) were cloned from the
      products of two crosses, phenotyped for their susceptibility to chloroquine, and
      genotyped for their inheritance of 46 chromosome-specific markers. No association
      was found between chloroquine susceptibility and the inheritance of pcmdr1, the
      P. chabaudi homologue of the pfmdr1 multi-drug resistance gene of P. falciparum.
      Also, there was no association between chloroquine susceptibility and the
      inheritance of a marker linked to a putative chloroquine resistance locus in a P.
      falciparum cross. However, 16 of the progeny clones showed co-segregation of four
      linked markers on chromosome 11 with their resistance phenotype. This result
      suggests that a locus for chloroquine resistance exists on this chromosome in P.
      chabaudi.

PMID- 9662029
TI  - Are tRNAs imported into the mitochondria of kinetoplastid protozoa as 5'-extended
      precursors?
AB  - All mitochondrial tRNAs in kinetoplastid protozoa are encoded in nuclear DNA and
      transported into the mitochondrion (Simpson et al., Nucl Acids Res 1989;17:5427
      5445; Hancock and Hajduk, J Biol Chem 1990;265:19208-19215). It has been proposed
      that tRNAs in these cells are imported into the mitochondrion as 5'-extended
      precursors which are processed by a mitochondrial RNase P-like activity (Hancock
      et al., J Biol Chem 1992;267:23963-23971). We have examined this hypothesis by
      cloning and sequencing primer extension products of mitochondrial tRNAs from
      Leishmania tarentolae and Trypanosoma brucei, and have found that these are
      derived from circularized mature tRNA molecules. We suggest that these molecules
      are produced by the endogenous RNA ligase activity (Bakalara et al., J Biol Chem
      1989;264:18679-18686) either in vivo or during mitochondrial isolation. We did
      not obtain any evidence for the existence of high molecular weight precursors of
      mitochondrial tRNAs. This negative result is consistent with previous in vivo
      transfection studies with both L. tarentolae (Lima and Simpson, RNA 1996;2:429
      440) and T. brucei (Hauser and Schneider, EMBO J 1995;14:4212-4220; Schneider et
      al., Mol Cell Biol 1994;14:2317-2322), in which mitochondrial targeting of
      plasmid-expressed tRNAs was independent of the presence of 5'-flanking sequences.
      We conclude that the hypothesis for 5'-extended tRNA precursors in kinetoplastid
      mitochondrial importation remains to be verified.

PMID- 9662030
TI  - Expression of substrate-specific transporters encoded by Plasmodium falciparum in
      Xenopus laevis oocytes.
AB  - When the malarial parasite Plasmodium falciparum multiplies in erythrocytes it
      dramatically increases uptake of essential metabolic precursors (nucleosides,
      nucleobases and glucose) and export of lactic acid by undefined mechanisms. The
      first evidence is provided here, by a detailed study in Xenopus laevis oocytes,
      that several specific nutrient transporters are the product of P. falciparum
      genes. We report the expression of nucleoside, nucleobase, hexose and
      monocarboxylate transport systems in Xenopus oocytes when injected with mRNA
      isolated from asexual stages of developing P. falciparum parasites. Their
      properties are distinct from transport events occurring at the infected
      erythrocyte membrane or the electrophysiologically identified channel localised
      to the parasitophorous vacuolar membrane. These novel transporters are substrate
      specific and stereoselective, and represent a key regulatory step in the
      acquisition and export of metabolites by intraerythrocytic P. falciparum.

PMID- 9662031
TI  - Arrest of Trypanosoma brucei rhodesiense and T. brucei brucei in the S-phase of
      the cell cycle by (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine ((S)-HPMPA).
AB  - African trypanosomes are incapable of purine de novo synthesis. They use salvage
      pathways to meet their purine requirements. Therefore, purine analogues appear as
      potential candidates to interfere in trypanosome metabolism. The acyclic
      adenosine analogue (S)-9-(-3-hydroxy-2-phosphonylmethoxypropyl)adenine ((S)
      HPMPA) expressed antitrypanosomal activity in vitro and vivo. When exposed to 20
      microM (S)-HPMPA, trypanosomes were arrested in the S-phase of the cell cycle and
      were unable to enter G2-phase. Thymidine uptake and incorporation was inhibited
      almost completely. Only nuclear DNA replication was inhibited, while
      mitochondrial DNA replication and kinetoplast division was not inhibited. The
      antitrypanosomal effect was reversible when cells were exposed for 12 h. As a
      control, aphidicolin arrested trypanosomes in the G1-phase of the cell cycle at a
      concentration of 30 microM. At 20 microM (S)-HPMPA, glycolysis was not effected,
      while leucine and adenine uptake were reduced with prolonged exposure.

PMID- 9662032
TI  - Two distinct groups of mucin-like genes are differentially expressed in the
      developmental stages of Trypanosoma cruzi.
AB  - Sialic acid acceptors of Trypanosoma cruzi are abundant mucin-like glycoproteins
      linked to the parasite membrane by a glycosylphosphatidyl inositol (GPI) anchor.
      They are heterogeneous and variable in different parasite stages. The protein
      portion of these mucins contains many threonine residues, and is thought to be
      encoded by a heterogeneous gene family. To investigate whether the high degree of
      heterogeneity in the mucin gene family is responsible for the diversity of mucins
      expressed on the parasite surface, we have studied the expression of mucin genes
      in several developmental stages of T. cruzi. We have found that mucins are
      expressed in all parasite stages. By using conserved sequences at 3' end of
      translated sequences of the gene family and the splice leader sequence, we have
      isolated 120 mucin-like cDNAs by RT-PCR from epimastigote and trypomastigote
      mRNAs. All transcribed genes contain conserved 5' and 3' regions, which code for
      the signal peptide, the sequence for GPI anchor addition, and a conserved domain
      rich in threonine residues. The internal portions of these genes are highly
      variable in size and sequence, and can be grouped in two major categories. One
      group contains KP(1-2)T(6-8) repeats, a motif found in mammalian mucins in the
      central region. This group is expressed preferentially in the trypomastigote
      forms ready to be released from the infected mammalian cell. The other has highly
      variable sequences in the central portion, and is expressed in all parasite
      stages. Because the number of synonymous substitutions is equivalent to the non
      synonymous substitutions in the second group, they are probably evolving
      neutrally. On the other hand, the KP(1-2)T(6-8) containing genes have more
      synonymous substitutions and are most likely under a strong selective pressure.
      We propose that the group of KP(1-2)T(6-8) motif corresponds to the highly
      glycosylated mucins of the trypomastigote stages. In the other group proteolysis
      may remove the central domain yielding small mucins, such as the mucins found in
      insect derived stages of T. cruzi.

PMID- 9662033
TI  - Changes in expression site control and DNA modification in Trypanosoma brucei
      during differentiation of the bloodstream form to the procyclic form.
AB  - We have adapted a system for in vitro differentiation of a monomorphic
      trypanosome strain to monitor changes in transcription and DNA modification in
      expression sites during the transition of the bloodstream-form to the procyclic
      trypanosome. We have used trypanosomes that have a gene for drug resistance
      integrated in an expression site, just downstream of either an expression site
      promoter, or a ribosomal promoter replacing the endogenous promoter. During the
      transition from bloodstream-form to procyclic, the promoters in an active
      expression site behave as expected on the basis of previous work on these
      promoters in procyclics, i.e. the ribosomal replacement promoter remains fully
      active, whereas the expression site promoter is (incompletely) down-regulated. A
      silent bloodstream-form expression site promoter does not remain tightly
      silenced, however. There is a transient increase of transcription of the marker
      gene during the transition from bloodstream-form to procyclic, indicating that
      the control of silent expression sites differs between the bloodstream-form and
      the procyclic trypanosome, and that a short time is required to reset the
      silencing mechanisms. One of the differences between bloodstream-form and
      procyclic trypanosomes is the presence of the modified base beta-D-glucosyl
      hydroxymethyluracil (J) in and around bloodstream-form expression sites. We have
      studied loss of this DNA modification and find that the change in expression site
      control from bloodstream-form to procyclic does not require active removal of J.
      Base J is lost by synthesis of new, unmodified DNA, which happens after the major
      changes in expression site transcription have occurred.

PMID- 9662034
TI  - Identification of a Meloidogyne incognita cuticle collagen gene and
      characterization of the developmental expression of three collagen genes in
      parasitic stages.

PMID- 9662035
TI  - Rotenone at high concentrations inhibits NADH-fumarate reductase and the
      mitochondrial respiratory chain of Trypanosoma brucei and T. cruzi.

PMID- 9662036
TI  - Sequence diversity in the intron, flanking sequences and coding region of the DNA
      polymerase alpha gene of Plasmodium falciparum.

PMID- 9662037
TI  - The novel core fucosylation of Haemonchus contortus N-glycans is stage specific.

PMID- 9662038
TI  - Effect of multiple downstream splice sites on polyadenylation in Trypanosoma
      brucei.

PMID- 9662039
TI  - Isolation of the cDNA encoding a dense granule associated antigen (NCDG2) of
      Neospora caninum.

PMID- 9662040
TI  - Insulin, insulin resistance and platelet function: similarities with insulin
      effects on cultured vascular smooth muscle cells.

PMID- 9662041
TI  - Studies on the betacellulin receptor in pancreatic AR42J cells.
AB  - Betacellulin is a member of the epidermal growth factor family and converts
      pancreatic AR42J cells into insulin-producing cells. This study was conducted to
      characterise the receptor for betacellulin in AR42J cells. AR42J cells expressed
      two classes of binding sites for radioactive iodine labelled betacellulin, with
      Kd values of 4.6 x 10(-11) mol/l and 3.0 x 10(-10) mol/l. The binding of
      [125I]betacellulin was inhibited by unlabelled betacellulin in a dose-dependent
      manner, but epidermal growth factor was 50 fold less effective than betacellulin.
      Affinity cross-linking showed a [125I]betacellulin-binding protein with a
      molecular weight of approximately 180 KDa. When this protein was
      immunoprecipitated with antibody against epidermal growth factor receptors ErbB
      1, ErbB-2, ErbB-3 or ErbB-4, it was immunoprecipitated only by the anti-ErbB-1
      antibody. When the [125I]betacellulin-labelled proteins were immunoprecipitated
      with a combination of the four ErbB antibodies, and the unprecipitated proteins
      were then immunoprecipitated with anti-phosphotyrosine antibody, a 190 KDa
      protein was observed. Betacellulin induced the tyrosine phosphorylation of ErbB
      1, ErbB-2 and ErbB-4. Finally, while 100 pmol/1 betacellulin converted all of the
      AR42J into insulin-producing cells in the presence of activin A, 10 nmol/l
      epidermal growth factor induced differentiation in only about 30 % of the cells.
      Higher concentrations of epidermal growth factor were less effective. Neu
      differentiation factor in the presence or absence of epidermal growth factor was
      ineffective. These results indicate that betacellulin binds to ErbB-1 and
      possibly another protein with a molecular weight of 190 KDa. The latter
      betacellulin-binding protein may be involved in the differentiation-inducing
      activity of betacellulin.

PMID- 9662042
TI  - Extra-insular beta cells associated with ductules are frequent in adult human
      pancreas.
AB  - Routine immunohistochemical analysis of human donor pancreata indicated the
      frequent occurrence of single insulin-immunoreactive cells. In a quantitative
      analysis of nine organs consecutively recruited from adult donors, 15 percent of
      all beta cells were found in units with a diameter less than < 20 microm and
      without associated glucagon-, somatostatin-, or pancreatic polypeptide cells.
      These single beta-cell units are located in or along ductules, from which they
      appear to bud as previously noticed in fetal and neonatal organs. They contain
      significantly smaller beta cells than endocrine aggregates with a larger
      diameter. The use of ductal cell markers such as cytokeratin 19, carbonic
      anhydrase-II and carbohydrate antigen 19.9 identified a close topographical
      association between ductal cells and budding beta cells; it also indicated that
      pancreatic lobules are composed of nearly one third ductal cells. The presence of
      Ki67 proliferation marker-immunoreactive ductal cells (0.05 %) and absence of
      Ki67-immunoreactive budding beta cells is compatible with the view that beta cell
      neogenesis depends on ductal cell proliferation and differentiation. The high
      proportion of budding beta cells in the adult human pancreas suggests the
      presence of numerous loci with a potential for beta cell neogenesis.

PMID- 9662043
TI  - Increased glucocorticoid sensitivity in islet beta-cells: effects on glucose 6
      phosphatase, glucose cycling and insulin release.
AB  - Glucose-6-phosphatase (G6Pase) activity and the rate of glucose cycling are
      increased in islets from animal models of Type II (non-insulin-dependent)
      diabetes mellitus. Glucocorticoid treatment further stimulates these processes
      and inhibits glucose-induced insulin release. To determine whether these effects
      result from a direct action of glucocorticoids on the beta-cells, we used
      isolated islets. The islets were from transgenic mice overexpressing the
      glucocorticoid receptor in their beta-cells to increase the cells' sensitivity to
      glucocorticoid. Islets from transgenic and non-transgenic control mice utilized
      and oxidized the same amount of glucose. In contrast, islet G6Pase activity was
      70 % higher, glucose cycling was increased threefold and insulin release was 30 %
      lower in islets from transgenic mice. Hepatic G6Pase activity was the same in
      transgenic and control mice. Dexamethasone administration increased G6Pase
      activity and glucose cycling and decreased insulin release in both transgenic and
      control mouse islets. We conclude that glucocorticoids stimulate islet G6Pase
      activity and glucose cycling by acting directly on the beta-cell. That activity
      may be linked to the inhibition of insulin release.

PMID- 9662044
TI  - Upregulation of hypothalamic nitric oxide synthase gene expression in
      streptozotocin-induced diabetic rats.
AB  - Plasma arginine vasopressin (AVP) is known to be elevated in patients with
      uncontrolled insulin-dependent diabetes mellitus who have plasma hyperosmolality
      with hyperglycaemia. Although osmotic stimuli cause an increase in nitric oxide
      synthase (NOS) activity as well as synthesis of AVP and oxytocin in the
      paraventricular (PVN) and supraoptic nuclei (SON), it is not known whether NOS
      activity in the hypothalamus changes in the diabetic patients who have plasma
      hyperosmolality with hyperglycaemia caused by insulin deficiency. Expression of
      the neuronal (n) NOS gene in the PVN and SON in streptozotocin (STZ)-induced
      diabetic rats was investigated by using in situ hybridization histochemistry and
      NADPH-diaphorase histochemical staining. Four weeks after intraperitoneal (i. p.)
      administration of STZ, male Wistar rats developed hyperglycaemia and plasma
      hyperosmolality. The expression of nNOS gene and NADPH-diaphorase staining in the
      PVN and SON remarkably increased in STZ-induced diabetic rats compared to control
      rats. Three weeks after administration of STZ, the diabetic rats were
      subcutaneously treated with insulin for 1 week, which resulted in significant
      suppression of the induction of nNOS, AVP and oxytocin gene expression in the PVN
      and SON. Furthermore, the induction of nNOS gene expression in the PVN and SON
      was suppressed in STZ-induced diabetic rats treated with phlorizin and diet to
      normalize hyperglycaemia without insulin treatment. These results suggest that
      upregulation of nNOS gene expression as well as AVP and oxytocin gene expression
      in the PVN and SON in STZ-induced diabetic rats may be associated with
      hyperglycaemia and plamsa hyperosmolality.

PMID- 9662045
TI  - Overexpression of mitochondrial FAD-linked glycerol-3-phosphate dehydrogenase
      does not correct glucose-stimulated insulin secretion from diabetic GK rat
      pancreatic islets.
AB  - Glucose-stimulated insulin secretion is impaired in GK (Goto-Kakizaki) rats,
      perhaps because of abnormalities in glucose metabolism in pancreatic islet beta
      cells. The glycerol phosphate shuttle plays a major role in glucose metabolism by
      reoxidizing cytosolic NADH generated by glycolysis. In the pancreatic islets of
      GK rats, the activity of mitochondrial FAD-linked glycerol-3-phosphate
      dehydrogenase (mGPDH), the key enzyme of the glycerol phosphate shuttle, is
      decreased and this abnormality may be responsible, at least in part, for impaired
      glucose-stimulated insulin secretion. To investigate this possibility, we
      overexpressed mGPDH in islets isolated from GK rats via recombinant adenovirus
      mediated gene transduction, and examined glucose-stimulated insulin secretion. In
      islets isolated from diabetic GK rats at 8 to 10 weeks of age, glucose-stimulated
      insulin secretion was severely impaired, and mGPDH activity was decreased to 79 %
      of that in non-diabetic Wistar rats. When mGPDH was overexpressed in islets from
      GK rats, enzyme activity and protein content increased 2- and 6-fold,
      respectively. Basal (3 mmol/l glucose) and glucose-stimulated (20 mmol/l) insulin
      secretion from the Adex1CAlacZ-infected GK rat islets were, respectively, 4.4 +/-
      0.7 and 8.1 +/- 0.7 ng. x islet(-1) x 30 min(-1), and those from mGPDH
      overexpressed GK rat islets 4.7 +/- 0.3 and 9.1 +/- 0.8 ng x islet(-1) x 30 min(
      1), in contrast to those from the AdexlCAlacZ-infected non-diabetic Wistar rat
      islets (4.7 +/- 1.6 and 47.6 +/- 11.9 ng x islet(-1) x 30 min(-1)). Thus, glucose
      stimulated insulin secretion is severely impaired in GK rats even in the stage
      when mGPDH activity is modestly decreased, and at this stage, overexpression of
      mGPDH cannot restore glucose-stimulated insulin secretion. We conclude that
      decreased mGPDH activity in GK rat islets is not the defect primarily responsible
      for impaired glucose-stimulated insulin secretion.

PMID- 9662046
TI  - Glucose modulation of ATP-sensitive K-currents in wild-type, homozygous and
      heterozygous glucokinase knock-out mice.
AB  - One type of maturity-onset diabetes of the young (MODY2) is caused by mutations
      in the glucokinase gene, a key glycolytic enzyme in the beta cell and liver.
      Glucose fails to stimulate insulin secretion in mice in which the glucokinase
      gene has been selectively knocked out in the beta cell. We tested the hypothesis
      that this effect results from defective metabolic regulation of beta cell ATP
      sensitive potassium (K(ATP)) channels. Glucose had little effect on K(ATP)
      currents in homozygous (-/-) mice but inhibited K(ATP) currents in wild-type
      (+/+) and heterozygous (+/-) mice with EC50 of 3.2 mM and 5.5 mM, respectively,
      in newborn animals, and of 4.7 mM and 9.9 mM, respectively, in 1.5-year-old mice.
      Glucose (20 mmol/l) did not affect the resting membrane potential of -/- beta
      cells but depolarised wild-type and + /- beta cells and induced electrical
      activity. In contrast, 20 mmol/l ketoisocaproic acid or 0.5 mmol/ l tolbutamide
      depolarised all three types of beta-cell. These results support the idea that
      defective glycolytic metabolism, produced by a loss (-/- mice) or reduction (+/-
      mice) of glucokinase activity, leads to defective K(ATP) channel regulation and
      thereby to the selective loss, or reduction, of glucose-induced insulin
      secretion.

PMID- 9662047
TI  - Streptozotocin-induced diabetes has differential effects on atrial natriuretic
      peptide synthesis in the rat atrium and ventricle: a study by solution
      hybridization-RNase protection assay.
AB  - In rats with streptozotocin (STZ)-diabetes for 2 or 4 weeks, the atrial
      natriuretic peptide (ANP) concentrations in the atria decreased whilst that of
      ANP in the plasma and ventricles increased. ANP concentrations in the
      hypothalamus and in the brainstem did not change in either 2- or 4-week diabetic
      rats. Atrial ANP content was partly restored by insulin replacement in 4-week
      diabetic rats. Plasma ANP concentrations and ventricular ANP contents were
      reversed to normal by insulin treatment in both 2- and 4-week diabetic rats.
      Solution-hybridization-RNase protection assay showed a significant increase in
      the preproANP mRNA expression in the ventricles but not in the atria. These
      results indicated that the STZ-diabetes increased the synthesis of ANP in the
      ventricles and consequently its release from the ventricles. The synthesis of ANP
      in the atria did not change as judged from the preproANP mRNA expression but the
      release of ANP from the atria might also be increased for ANP content decreased
      in the atria. The reason for the difference in the response of atrial and
      ventricular preproANP concentrations to STZ-diabetes is not known.

PMID- 9662048
TI  - Predictors of IDDM recurrence risk in offspring of Danish IDDM patients. Danish
      IDDM Epidemiology and Genetics Group.
AB  - It has previously been observed that offspring of mothers with insulin-dependent
      diabetes mellitus (IDDM) have a lower risk of IDDM than offspring of IDDM
      affected fathers. To assess the offspring IDDM recurrence risk in a Danish
      population-based study and to investigate parental and offspring-related
      biological variables that might influence this risk, we identified 2726 IDDM
      probands and their 2826 offspring from a background population of 1.725 million
      people (33% of the Danish population). Current age of probands was 20-65 years
      and their age at IDDM onset was 30 years or less. Sixty-nine offspring (2.4%)
      were affected with IDDM. The sex difference in the parental-offspring IDDM
      transmission rate was confirmed. The cumulative IDDM risk up to age 30 years was
      found to be significantly decreased in maternal offspring compared to paternal
      offspring (2.3 +/- 0.6 and 5.7 +/- 0.9 %, RR = 2.40, 95% CI 1.30-4.47; p = 0.004)
      only if parents were diagnosed with IDDM before birth of the offspring. However,
      due to the low number of diabetic offspring of probands diagnosed with IDDM after
      offspring birth, this observation needs to be confirmed in a larger population.
      In a subpopulation of the 2380 offspring, whose parents were all diagnosed with
      IDDM before offspring birth, the recurrence risk was significantly increased in
      offspring of male probands diagnosed up to age 17 years compared to offspring of
      fathers diagnosed at older ages (8.5 +/- 1.8 and 3.6 +/- 1.0%; RR = 2.27, 95% CI
      1.21-4.25; p = 0.006). No such relation was found in maternal offspring. Using
      the Cox proportional hazards model on this offspring subpopulation we found that
      paternal age at IDDM onset was the only statistically significant predictor of
      IDDM recurrence risk. Our findings may be important for counselling families in
      which one parent has IDDM.

PMID- 9662049
TI  - Differential expression of receptors for advanced glycation end products on
      monocytes in patients with IDDM.
AB  - Accelerated modification of proteins by glucose terminating in the formation of
      advanced glycation endproducts (AGEs) is one of the main pathogenetic mechanisms
      of diabetes-associated complications. One pathway by which AGEs may exert their
      effects is by interaction with specific receptors initially identified on
      macrophages, monocytes and endothelial cells. As AGE-induced autocrine
      upregulation of AGE receptors has been observed in vitro, we hypothesized that
      AGE-binding might be enhanced in diabetic patients to compensate for the elevated
      levels of circulating AGEs. We therefore examined the expression of AGE-binding
      sites on peripheral monocytes, serum levels of AGEs and AGE-induced cytokine
      production in patients with insulin-dependent diabetes mellitus (IDDM) compared
      to age-matched, healthy control subjects. In patients, AGE-binding capacity was
      significantly increased and there was only one class of binding sites, as
      revealed by Scatchard analysis (1.8 x 10(5) vs 1.4 x 10(5) binding sites per
      cell). Affinity of binding was, however, similar (Ka 1.5 x 10(6) vs 1.4 x 10(6)
      mol(-1)). Saturation of binding was reached at 2.0-3.0 micromol/l with AGE-bovine
      serum albumin (BSA) as ligand. In contrast, cytometry using fluorescein
      isothiocyanate-labelled AGE-proteins showed no saturability and reversibility of
      AGE-binding up to 80 micromol/l, indicating non-specific binding in this
      concentration range. Again, this non-specific binding was significantly higher in
      IDDM patients. In addition, we found much higher levels of circulating AGEs in
      patients as compared to controls and studied possible functional consequences of
      increased AGE binding in vitro, monocyte stimulation by AGEs triggering cytokine
      release to a similar extent in patients and controls, i.e. independently of the
      AGE-binding capacity. Our finding of an enhanced overall AGE-binding capacity of
      peripheral monocytes in IDDM could be instrumental in limiting the plasma
      concentration of AGEs, the non-specific binding coming into play after saturation
      of specific binding sites by higher plasma AGE-levels. Both binding strategies
      may act in concert as "damage limitation mechanisms" in the development of AGE
      dependent diabetic complications.

PMID- 9662050
TI  - Comparison of a novel micro-assay for insulin autoantibodies with the
      conventional radiobinding assay.
AB  - Measurement of insulin autoantibodies (IAA) with a novel micro radiobinding assay
      which requires only 20 microl of serum was compared with that in a conventional
      radiobinding assay which uses 600 microl of serum. IAA were measured with both
      assays in samples from 94 new onset insulin-dependent diabetes mellitus (IDDM)
      patients, 97 control subjects. and 48 first degree relatives of IDDM patients
      selected for having IAA in the conventional radiobinding assay. Overall, 227
      (95%) of 239 samples tested were concordant. and IAA levels correlated well (r2 =
      0.7) between the two assays. Discordant results were obtained in 7 new onset
      patients, 4 control subjects, and 1 first degree relative, and these had low IAA
      levels in the respective assays. Sensitivity and specificity in the new onset
      IDDM patients and control subjects were 69% and 98% for the micro radiobinding
      assay and 72% and 98% for the conventional radiobinding assay. The use of the
      micro radiobinding assay should greatly facilitate islet related antibody
      screening, particularly in children.

PMID- 9662051
TI  - Plasma homocysteine is related to albumin excretion rate in patients with
      diabetes mellitus: a new link between diabetic nephropathy and cardiovascular
      disease?
AB  - The high risk of cardiovascular disease in patients with diabetes mellitus,
      particularly in those with nephropathy, is not completely explained by classical
      risk factors. A high plasma homocysteine concentration is an independent risk
      factor for cardiovascular disease but information on its association with
      diabetes is limited. Fasting homocysteine concentrations were measured in the
      plasma of 165 diabetic patients (75 with insulin-dependent [IDDM]; 90 with non
      insulin-dependent diabetes [NIDDM]) and 56 non-diabetic control subjects. Other
      measurements included the prevalence of diabetic complications, glycaemic
      control, lipid and lipoprotein levels, vitamin status and renal function tests.
      Patients with NIDDM had higher homocysteine levels than control subjects, whereas
      IDDM patients did not (9.2 +/- 4.5 vs 7.7 +/- 2 micromol/l, p < 0.01; and 7.0 +/-
      3 vs 7.4 +/- 2 micromol/l, NS). Univariate correlations and multiple regression
      analysis showed albumin excretion rate to be the parameter with the strongest
      independent association with homocysteine. Patients with both types of diabetes
      and nephropathy had higher plasma homocysteine concentrations than those without
      nephropathy. Increases of homocysteine in plasma were related to increases in the
      severity of the nephropathy. Fasting hyperhomocysteinaemia was considered as the
      mean of the plasma homocysteine for all control subjects (7.5 +/- 2.1 micromol/l)
      + 2 SD (cut-off = 11.7 micromol/l). Nephropathy was present in 80 % of diabetic
      patients with fasting hyperhomocysteinaemia. In conclusion, increases in fasting
      homocysteine in diabetic patients are associated with increased albumin excretion
      rate, especially in those with NIDDM, thus providing a potential new link between
      microalbuminuria, diabetic nephropathy and cardiovascular disease.

PMID- 9662052
TI  - Microalbuminuria is strongly associated with NIDDM and hypertension, but not with
      the insulin resistance syndrome: the Hoorn Study.
AB  - Microalbuminuria is a strong predictor of cardiovascular disease. The aim of this
      study was to investigate whether microalbuminuria is part of a cluster of risk
      factors, the insulin resistance syndrome (IRS), or whether it is only associated
      with, and presumably a complication of, hypertension and non-insulin-dependent
      diabetes mellitus (NIDDM). An age-, sex- and glucose tolerance-stratified random
      sample from a 50-75 year old general population (n = 622) was investigated. The
      urinary albumin-to-creatinine ratio was measured in an early morning spot urine
      sample. Microalbuminuria was defined as an albumin-to-creatinine ratio greater
      than 2.0 mg/ mmol. We considered, as IRS-related variables, fasting
      hyperinsulinaemia, insulin resistance (IR; calculated from the formula of the
      homeostasis model assessment), dyslipidaemia, glucose intolerance, hypertension
      and waist-to-hip ratio (WHR). Dyslipidaemia was defined as levels of HDL
      cholesterol in the lowest and/or levels of triglyceride in the highest tertile.
      Fasting insulin levels, IR and WHR were divided into tertiles; the highest
      tertiles were compared to the lowest tertiles. Age-, sex- and glucose tolerance
      adjusted analyses showed microalbuminuria to be significantly associated with
      hypertension, NIDDM and WHR. In multiple logistic regression analyses,
      microalbuminuria showed independent associations with hypertension, NIDDM and
      WHR, with odds ratios (ORs [95% confidence interval]) of 3.33 (1.86-5.96), 2.26
      (1.14-4.48) and 2.49 (1.09-5.70), respectively. No associations were found with
      impaired glucose tolerance, hyperinsulinaemia, IR or dyslipidaemia. Multiple
      logistic regression analyses in diabetic and non-diabetic subjects separately
      showed that microalbuminuria was independently associated only with hypertension
      (ORs 4.31 and 2.69). In this Caucasian population, microalbuminuria was
      associated with hypertension, NIDDM and WHR and not with other variables of the
      IRS. It is therefore likely that microalbuminuria is a complication of
      hypertension and NIDDM, and not an integral part of the IRS.

PMID- 9662053
TI  - Organization of the human carboxypeptidase E gene and molecular scanning for
      mutations in Japanese subjects with NIDDM or obesity.
AB  - Insulin is synthesized in the pancreatic beta cell as a larger precursor molecule
      proinsulin which is converted to insulin and C-peptide by the concerted action of
      prohormone convertase 2 (PC2), prohormone convertase 3 (PC3) and carboxypeptidase
      E (CPE). One of the features of non-insulin-dependent diabetes mellitus (NIDDM)
      is an elevation in the proinsulin level and/or proinsulin/insulin molar ratio
      suggesting that mutations in these three proinsulin processing enzymes might
      contribute to the development of NIDDM. The identification of a mutation in the
      CPE gene of the fat/fat mouse which leads to marked hyperproinsulinaemia and late
      onset obesity and diabetes is consistent with a possible role for mutations in
      CPE in the development of diabetes and obesity in humans. In order to test this
      hypothesis, we have isolated and characterized the human CPE gene and screened it
      for mutations in a group of Japanese subjects with NIDDM and obesity. The human
      CPE gene consists of 9 exons spanning more than 60 kb. Primer extension analysis
      identified the transcriptional start site at -141 bp from the translational start
      site. Single strand conformational polymorphism analysis and nucleotide
      sequencing of the promoter and entire coding region of the CPE gene in 269
      Japanese subjects with NIDDM, 28 nondiabetic obese subjects and 104 nonobese and
      nondiabetic controls revealed three nucleotide changes, a G-to-T substitution at
      nucleotide -53, a G-to-A substitution at nucleotide -144 (relative to start of
      transcription) in the promoter region and a silent G-to-A substitution in codon
      219. None of the nucleotide substitutions were associated with NIDDM or obesity.
      Thus, genetic variation in the CPE gene does not appear to play a major role in
      the pathogenesis of NIDDM or obesity in Japanese subjects.

PMID- 9662054
TI  - Relationship between fasting plasma glucose, atherosclerosis risk factors and
      carotid intima media thickness in non-diabetic individuals.
AB  - We analysed the relationship between fasting plasma glucose, carotid intima media
      thickness and some atherosclerosis risk factors in 307 non-diabetic individuals.
      Male (n = 120) and female subjects (n = 187) with a familial history of Type II
      diabetes mellitus and/or obesity and hyperlipoproteinaemia were examined in the
      age group 40-70 years. Plasma triglycerides, total and high-density-lipoprotein
      cholesterol, plasminogen activator inhibitor were measured by conventional
      methods. Specific insulin, pro-insulin and C-peptide were measured by specific
      enzyme immunoassay. Intima media thickness increased in quintiles for fasting
      plasma glucose in men, but not in women. There was a rise of triglycerides, body
      mass index, waist to hip ratio, plasminogen activator inhibitor, true insulin,
      proinsulin, C-peptide and a decrease of high-density-lipoprotein cholesterol in
      quintiles for fasting plasma glucose. Fasting plasma glucose was found to be
      significantly positively correlated to intima media thickness, body mass index,
      waist to hip ratio, haemoglobin A1c, insulin, C-peptide, triglycerides,
      plasminogen activator inhibitor and significantly negatively correlated to high
      density lipoprotein cholesterol. However, the correlation of fasting plasma
      glucose to intima media thickness was no longer significant after adjustment for
      age and sex. After adjustment for age and sex intima media thickness was
      significantly correlated to body mass index, total cholesterol, triglycerides,
      albuminuria and inversely correlated to high-density-lipoprotein cholesterol. In
      multivariate analysis age, male sex, high-density-lipoprotein cholesterol and
      total cholesterol were significant determinants of intima media thickness. Our
      data suggest that a weak association exists between fasting plasma glucose and
      intima media thickness, which may be mediated by a clustering of risk factors in
      the upper range of non-diabetic fasting plasma glucose level with a central role
      for dyslipidaemia.

PMID- 9662055
TI  - Cognitive function testing in studies of acute hypoglycaemia: rights and wrongs?

PMID- 9662056
TI  - Shift of glycaemic thresholds for cognitive function in hypoglycaemia unawareness
      in humans.

PMID- 9662057
TI  - Does insulin-induced increase in the amount of plasma membrane GLUTs
      quantitatively account for insulin-induced increase in glucose uptake?

PMID- 9662058
TI  - Cellular immune responses to beta casein: elevated in but not specific for
      individuals with Type I diabetes mellitus.
AB  - Elevated cellular immune responses against the cows' milk protein beta casein
      have been reported in individuals with Type I diabetes mellitus, a finding
      supportive of the concept that cows' milk consumption may be causative for the
      disease. We analysed cellular immune reactivities against beta casein in newly
      diagnosed Type I diabetic patients, their immediate autoantibody negative
      relatives, and unrelated healthy individuals in order to further elucidate the
      role of anti-beta casein immunity in the pathogenesis of Type I diabetes
      mellitus. Peripheral blood mononuclear cells were stimulated in vitro with
      various concentrations of three different beta casein preparations, control
      antigens (tetanus toxoid, mumps extract) and a mitogen (phytohemagglutinin). The
      frequency and/or mean simulation index of cellular proliferation against two of
      the beta casein preparations at high antigen concentrations (i.e. 10 or 50
      microg/ml) were significantly higher in newly-diagnosed Type I diabetic subjects
      compared with autoantibody negative healthy control subjects. However,
      reactivities against beta casein in the Type I diabetic probands and their
      autoantibody negative relatives, individuals with a very low-rate of disease
      development, were almost identical. Cellular immune reactivities to other
      antigens were similar between the subject groups. In addition to indicating the
      need for appropriately matched subject populations (e.g. human leukocyte antigen
      (HLA) matched relatives) when analysing cellular immune responses, these findings
      support our previous contention that individuals genetically prone to
      autoimmunity may be deficient in forming tolerance to dietary antigens. However,
      the significance of anti-beta casein immunity as a specific causative factor in
      the pathogenesis of Type I diabetes mellitus remains unclear.

PMID- 9662059
TI  - Transduction of non-dividing adult human pancreatic beta cells by an integrating
      lentiviral vector.
AB  - Pancreatic islet cells are terminally differentiated endocrine cells and are
      refractory to stable infection by retroviral vectors, which require the breakdown
      of the nuclear membrane during cell division in order to insert the transgene
      into the host cell genome. Thus, attempts to render beta-cell allografts less
      immunogenic have had to rely on stable transfection of surrogate cells.
      Similarly, this problem has precluded the development of conditionally
      immortalized human beta cells for clinical allotransplantation. In this report,
      we demonstrate that adult human islet beta cells can be transduced by a new three
      plasmid integrating lentiviral vector with an efficiency of 62 +/- 1.8 % at a
      multiplicity of infection (MOI) of 2.5 in vitro. This work makes genetic
      engineering of adult human pancreatic beta cells possible for the first time,
      allowing strategies to render beta-cell allografts non-immunogenic to be
      optimized and to creating conditionally immortalized human beta cells for
      clinical transplantation.

PMID- 9662060
TI  - Importance of searching for mtDNA defects in patients with diabetes and hearing
      deficit.

PMID- 9662061
TI  - Effect of angiotensin II and bradykinin on insulin-stimulated tyrosine kinase
      activity of insulin receptor.

PMID- 9662062
TI  - Group specific component protein genotype is associated with NIDDM in Japan.

PMID- 9662063
TI  - Possible risk of sulphonylureas in the treatment of non-insulin-dependent
      diabetes mellitus and coronary artery disease.

PMID- 9662064
TI  - Protein kinases entering the information age.

PMID- 9662065
TI  - Molecular profiling of tyrosine kinases in normal and cancer cells.
AB  - As the post-genome era is approaching, with vast amount of sequence information
      available and new technology developed, scientists are presented with
      opportunities to explore in simple analysis the structure and expression pattern
      of not just a single gene, but of an entire family of genes, if not the entire
      genome. The concept of 'molecular profiling' or 'expression array' has thus
      emerged. The need to simultaneously 'see' all genes in the same family is obvious
      under the precept of the combinatorial process being an underlying principle of
      complex biological systems: no gene exists in isolation, for virtually every
      molecule participates in intermolecular interactions. The activation of receptor
      tyrosine kinases through homo or hetero-dimerization is the prototypic example.
      In this review, a tyrosine kinase profile technique and its application to
      studying the expression of tyrosine kinases and the identification of novel
      kinases will be discussed. This serves as an introduction to the several
      interesting papers published in this special 'kinase' issue of the Journal of
      Biomedical Sciences, using this technique. A new simplified approach, kinase
      display, which is an extension of the profiling method and requires only
      restriction digestion and gel analysis will also be introduced.

PMID- 9662066
TI  - Activation of STAT transcription factors in oncogenic tyrosine kinase signaling.
AB  - Signal transducers and activators of transcription (STATs) are cytoplasmic
      transcription factors that translocate to the nucleus and regulate gene
      expression in response to cytokine and growth factor stimulation. Emerging
      evidence indicates that STAT signaling is also frequently activated by oncogenes
      and in tumor cells. Constitutive activation of STAT proteins has been reported in
      cell lines stably transformed by diverse oncoproteins that directly or indirectly
      activate specific tyrosine kinase signaling pathways. In addition, STAT
      activation has been detected in a variety of human tumors and tumor cell lines,
      many of which are known to harbor activated tyrosine kinases. Recent findings
      support a model in which activation of STAT signaling in the context of
      oncogenesis induces gene expression that participates in malignant
      transformation.

PMID- 9662067
TI  - Digital cloning: identification of human cDNAs homologous to novel kinases
      through expressed sequence tag database searching.
AB  - Identification of novel kinases based on their sequence conservation within
      kinase catalytic domain has relied so far on two major approaches, low-stringency
      hybridization of cDNA libraries, and PCR method using degenerate primers. Both of
      these approaches at times are technically difficult and time-consuming. We have
      developed a procedure that can significantly reduce the time and effort involved
      in searching for novel kinases and increase the sensitivity of the analysis. This
      procedure exploits the computer analysis of a vast resource of human cDNA
      sequences represented in the expressed sequence tag (EST) database. Seventeen
      novel human cDNA clones showing significant homology to serine/threonine kinases,
      including STE-20, CDK- and YAK-related family kinases, were identified by
      searching EST database. Further sequence analysis of these novel kinases obtained
      either directly from EST clones or from PCR-RACE products confirmed their
      identity as protein kinases. Given the rapid accumulation of the EST database and
      the advent of powerful computer analysis software, this approach provides a fast,
      sensitive, and economical way to identify novel kinases as well as other genes
      from EST database.

PMID- 9662068
TI  - Tyrosine kinase expression profiles of chicken erythro-progenitor cells and
      oncogene-transformed erythroblasts.
AB  - Tyrosine kinases are implicated in the growth and differentiation of erythroid
      cells. Aberrant expression and structural alterations of certain tyrosine
      kinases, such as erbB and sea, are known to trigger erythroleukemia development.
      To facilitate our understanding of the signal transduction pathways involved in
      erythroid differentiation and leukemic transformation, we have applied a recently
      developed tyrosine kinase profile technique to identify the tyrosine kinases and
      some novel serine/threonine kinases expressed in normal chicken erythroid
      progenitor cells that respond to TGFalpha (TGFalpha-EB), and erythroblasts
      transformed by viruses encoding v-erbB (v-erbB-EB) and v-sea (v-sea-EB). Our
      results reveal that the non-receptor tyrosine kinases, Abl, Fyn, Lyn, Btk and
      Csk, are expressed in all three cell types. The expression level of Btk, a
      tyrosine kinase implicated in Bruton's syndrome, is exceptionally high in the
      erythroblastoid cell line 6C2, transformed by the v-erbB carrying avian
      erythroblastosis virus, AEV-ES4. We have also uncovered a new STE-20-related
      serine/threonine kinase, KFC, which is abundantly expressed in both the TGFalpha
      stimulated erythroid progenitor cells and v-sea-transformed erythroblasts. Based
      on sequence homology of the kinase domain, KFC appears to be the first member of
      a new subfamily of STE-20-like kinases.

PMID- 9662069
TI  - Protein-tyrosine kinase and protein-serine/threonine kinase expression in human
      gastric cancer cell lines.
AB  - Protein kinases play key roles in cellular functions. They are involved in many
      cellular functions including; signal transduction, cell cycle regulation, cell
      division, and cell differentiation. Alterations of protein kinase by gene
      amplification, mutation or viral factors often induce tumor formation and tumor
      progression toward malignancy. The identification and cloning of kinase genes can
      provide a better understanding of the mechanisms of tumorigenesis as well as
      diagnostic tools for tumor staging. In this study, we have used degenerated
      polymerase-chain-reaction primers according to the consensus catalytic domain
      motifs to amplify protein kinase genes (protein-tyrosine kinase, PTK, and protein
      serine/threonine kinase, PSK) from human stomach cancer cells. Following
      amplification, the protein kinase molecules expressed in the gastric cancer cells
      were cloned into plasmid vectors for cloning and sequencing. Sequence analysis of
      polymerase-chain-reaction products resulted in the identification of 25 protein
      kinases, including two novel ones. Expression of several relevant PTK/PSK genes
      in gastric cancer cells and tissues was further substantiated by RT-PCR using
      gene-specific primers. The identification of protein kinases expressed or
      activated in the gastric cancer cells provide the framework to understand the
      oncogenic process of stomach cancer.

PMID- 9662070
TI  - Differential expression of protein kinases in cultured primary neurons derived
      from the cerebral cortex, hippocampus, and sympathetic ganglia.
AB  - Protein kinases play pivotal roles in the development of the nervous system. They
      are involved in almost every stage of neuronal development, from initial
      proliferation and differentiation of progenitor cells to pathfinding of neurites
      and formation of synapses. Activation of protein kinases is also critical for
      neuronal cell survival. To gain further insights into kinases in neural
      development, we studied the expression patterns of protein kinases in three
      cultured primary neurons by degenerate primer-based reverse transcription
      polymerase chain reaction (PCR) and DNA sequencing, taking advantage of all known
      kinases containing a conserved catalytic domain. Our data demonstrated that the
      expression patterns of kinases in various cultured neurons are not only different
      from those of non-neural tissues, but also distinct among neurons derived from
      discrete origins. For example, FGF receptor 1 is predominantly expressed in
      hippocampal neurons. As this approach may be biased during PCR and cloning steps,
      an RNase protection assay was employed to verify the expression levels of six
      kinases in cultured neurons. Results from the RNase protection assay did
      generally confirm those obtained by the PCR-based method. However, quantitative
      nature of the latter was dependent on numbers of clones analyzed, and discrepancy
      of expression levels of kinases detected by the two methods was sometimes
      observed.

PMID- 9662071
TI  - Identification of immune-related protein kinases from mosquitoes (Aedes aegypti).
AB  - Protein kinases are known to be involved in signal transduction for numerous
      physiological events. However, little is known about the roles of protein kinases
      in insect immunity. A fragment around 150 bp was amplified by polymerase chain
      reaction using cDNA templates from bacterial inoculated mosquitoes and primers
      corresponding to the conserved domain of protein kinases. Based on sequence
      analysis, 11 groups of protein kinases were characterized including 3 nonreceptor
      tyrosine kinases, 3 receptor tyrosine kinases, 3 serine/threonine kinases, and 2
      novel protein kinases. The most abundant kinase obtained in this study reveals a
      high degree of similarity to human cholinesterase-related cell division
      controller (CHED) protein kinase. The expression of this mosquito CHED-like
      kinase is not detectable in normal female mosquitoes, but induced only after
      bacterial inoculation and trauma. A mosquito protein kinase was demonstrated to
      share homology with a plant Tousled gene, but has not yet been characterized in
      the animal system. In addition, analysis of the sequences of several protein
      kinases cloned from mosquitoes suggests that they might be involved in the
      regulation of cellular or humoral immunity.

PMID- 9662072
TI  - Isolation and identification of novel protein kinase genes from the round-spotted
      pufferfish (Tetraodon fluviatilis) genomic DNA.
AB  - The round-spotted pufferfish Tetraodon fluviatilis has a genome size of 380 Mb
      which is slightly smaller than that of another pufferfish, Fugu rubripes rubripes
      (Fugu). Due to their compact genome and small introns, both pufferfishes have
      been proposed as model organisms for genome studies. In this study, we have used
      genomic DNA as template to perform PCR to screen for protein kinase (pk) genes.
      Forty-one T. fluviatilis pk genes encoding 7 receptor tyrosine kinases, 14
      nonreceptor tyrosine kinases, 16 serine/threonine kinases, 1 dual kinase and 3
      novel kinases have been identified. The success of this approach depends on the
      size and location of the introns. Most of the identified pk gene fragments
      contain introns, ranging from 71 to 300 bp, with an average of 120 bp. It is
      noteworthy that the intron/exon boundaries of certain genes which belong to the
      same family are identical. We also analyzed by specific RT-PCR primers the
      expression profile of those 3 novel genes as well as some selected pk genes in a
      variety of tissues. We found that erbB3, pku a, mrk, CaMK I, CaMKIIgamma, and two
      novel kinase genes (133 and 3-26) are expressed in all tissues examined. However,
      the novel clone 146 is strongly expressed in the brain and weakly in the
      intestine, kidney and heart.

PMID- 9662073
TI  - From mosquito to man: identification of a novel protein kinase, HsHPK, which is
      highly expressed in human hepatoma tissues.
AB  - Protein kinases play an important role in the signaling pathway of growth factors
      in most of the higher organisms. During the study of protein kinase profiles of
      mosquitoes using RT-PCR and degenerate primers for consensus catalytic domain
      motifs to amplify protein kinase genes, we have noticed that a novel mosquito
      kinase, AaPK-38, shares a stretch of amino acids identical to the corresponding
      domain in Tousled gene of Arabidopsis thaliana that is required for leaf and
      flower development. A 2.1-kb cDNA encoding human HsHPK gene, which is a homolog
      of AaPK-38, was isolated from human testis cDNA library. This cDNA contains an
      open reading frame of 563 amino acids, with a complete kinase domain in its
      carboxyl terminus. The expressed Flag-tagged HsHPK was shown to have kinase
      activity based on in vitro autophosphorylation. Northern blot analysis revealed
      that human HsHPK mRNA is most abundant in testes, much less in heart and skeletal
      muscle and almost undetectable in liver and lung. Finally, we found that the
      expression of HsHPK in 4 out of 6 human hepatoma tissues is much higher than that
      in the adjacent normal counterpart. This result suggests HsHPK may play a role in
      the development of human hepatoma.

PMID- 9662074
TI  - Cloning, expression and chromosomal localization of human Ca2+/calmodulin
      dependent protein kinase kinase.
AB  - A human cDNA clone encoding the calcium/calmodulin-dependent protein kinase
      kinase (CaMKK) was isolated by RT-PCR amplification of the fragment corresponding
      to the conserved kinase catalytic domain followed by rapid amplification of cDNA
      ends and cDNA library screening. Compilation of nucleotide sequencing data
      yielded a consensus cDNA sequence of 1.9 kb with an open reading frame of 1,251
      nucleotides in length which translates to a polypeptide of 417 amino acids (47
      kd). It showed significant homology to the rat brain CaMKK isozymes. The human
      CaMKK, which was expressed as a Flag-tagged protein in human non-small cell lung
      cancer H- 1299 cells followed by immunoprecipitation with anti-Flag antibody, was
      shown to phosphorylate recombinant human CaMK I in a calcium/CaM-dependent
      fashion. Northern blot analysis revealed that human CaMKK is ubiquitously
      expressed, with brain showing the highest level of expression. The CaMKK gene is
      localized to human chromosome 12. The presence of cDNA clones with divergent 3'
      terminal sequences suggests a family of CaMKK variants which may arise from
      alternative splicing.

PMID- 9662075
TI  - Y chromosome, urinary chemosignals, and an agonistic behavior (offense) of mice.
AB  - In mice, offense is one type of agonistic behavior associated with attacks.
      Offense of male mice was measured in a panel of testers design. The mice were
      DBA1 (D1) and DBA1.C57BL10-Y (D1.B10-Y). These are congenic for the male
      specific, nonrecombining part of the Y chromosome. For the behavioral
      experiments, urine from D1 or D1.B10-Y mice was daubed on gonadectomized
      opponents. The opponents were of two genotypes, D1 or D1.B10-Y. The experimental
      subjects were of the same two genotypes. There were main effects for strain of
      experimental subject and strain of urine donor as well as interactions for strain
      of experimental subject x strain of gonadectomized opponent, strain of
      gonadectomized opponent x strain of urine donor, and strain of experimental
      subject x strain of gonadectomized opponent x strain of urine donor. These
      findings are consistent with a model in which this part of the Y chromosome
      affects testosterone-dependent pheromones and non-testosterone-dependent odor
      types acting as motivating stimuli, the olfactory perception of motivating
      stimuli for offense, and the motivational mechanism for offense.

PMID- 9662076
TI  - Chemosensory learning in the chicken embryo.
AB  - Prenatal chemosensory learning has been demonstrated in mammals, fish,
      amphibians, and insects, but not birds, although there is evidence of the avian's
      ability to learn auditory stimuli before hatching. This paper examines how
      exposure to a chemosensory stimulus (strawberry) prior to hatching affects
      subsequent chemosensory preferences of newly hatched chicks. The chicks'
      preferences were assessed at 2 days after hatching using an "olfactory"
      preference test (strawberry-smelling shavings versus water-coated shavings) and
      at 4 days after hatching using a "gustatory" preference test (strawberry
      flavoured water versus unflavoured water). Chicken embryos were exposed to
      strawberry from Day 15 to Day 20 of incubation by either presenting the odour in
      the air around the egg, rubbing it onto the shell, or injecting it into the air
      space. With no exposure to strawberry before hatching, strawberry was highly
      aversive to chicks after hatching. However, following exposure to strawberry
      before hatching, chicks expressed a greater preference for (or weaker aversion
      to) the strawberry stimulus. Chicks exposed to strawberry before hatching drank
      more strawberry-flavoured water and spent more time in a strawberry-scented area
      than chicks having no exposure before hatching. This change in preference was
      specific to the stimulus experienced before hatching and was present in the
      absence of any posthatching exposure to the stimulus. The results demonstrate
      that a chick's chemosensory preferences are changed as a result of experience
      with a stimulus before hatching and are suggestive of learning. The results,
      similar to those obtained in other animal groups, indicate the universality of
      "prenatal" chemosensory learning in the animal kingdom. A possible role of
      embryonic chemosensory learning for recognition is discussed.

PMID- 9662077
TI  - Food intake responses to upper gastrointestinal lipid infusions in humans.
AB  - Previous studies in humans and animals have shown that the presence of lipid in
      the small intestine can reduce food intake. Studies that have combined
      intraduodenal lipid infusions with gastric distension produced a greater
      reduction in food intake than when these two stimuli were separated. In this
      study, subjects received duodenal lipid (Intralipid 20%) infusions for varying
      periods before and during the consumption of a liquid test meal. The aim of this
      procedure was to maximise the interaction between intestinal nutrient stimulation
      and gastric distension. A dose-dependent decrease in food intake was observed
      that corresponded to the duration of infusion; 90- (180 kcal) and 45-min (90
      kcal) infusions but not 15-min (30 kcal) infusions significantly reduced intake
      compared to saline. These results show that concomitant intestinal nutrient
      stimulation and gastric distension is an effective test for the measurement of
      suppression of food intake by intestinal nutrients.

PMID- 9662078
TI  - Propylthiouracil tasting as a possible genetic association marker for two types
      of alcoholism.
AB  - The ability to taste 6-n-propylthiouracil (PROP) as bitter is determined
      genetically. The present study investigated whether this genetic ability was
      correlated with alcoholism and/or depression. Four groups of community college
      students (n = 25 each) were constituted based on the presence or absence of
      alcoholism and/or depression in themselves or their parents. Family history was
      assessed using the Family History-Research Diagnostic Criteria. Each subject was
      given a taste test using paper saturated with PROP. The results showed that
      subjects who had only alcoholism in their family were more likely to be
      nontasters of PROP than the control group, whereas subjects with both alcoholism
      and depression in their family were more likely to be so-called supertasters of
      PROP; that is, they found it extremely bitter. These findings suggest that PROP
      tasting might function as a genetic marker for two types of alcoholism.

PMID- 9662079
TI  - Behavioral and electromyographic characterization of the local frequency of
      tacrine-induced tremulous jaw movements.
AB  - Rats were implanted with fine-wire electromyograph (EMG) electrodes and were
      videotaped to identify the local frequency characteristics and muscle activity
      associated with tacrine-induced tremulous jaw movements. All rats received
      intraperitoneal injections of 2.5 mg/kg tacrine. The videotape sessions were
      played back in slow motion (i.e., one-sixth normal speed), and an observer
      entered each jaw movement into a computer program that recalculated the
      interresponse time and the local frequency (in hertz) for each movement within a
      burst. Analyses of the distribution of frequencies showed that the peak frequency
      of jaw movements was in the 3- to 5-Hz frequency range, with an average frequency
      of 4.0 Hz. EMG electrodes were implanted into three jaw muscles: temporalis,
      anterior belly of digastricus, and masseter. Tremulous jaw movements were not
      accompanied by consistent changes in masseter activity. The anterior belly of
      digastricus showed bursts of EMG activity during some jaw movements, although the
      temporal relation between jaw movements and EMG activity was somewhat
      inconsistent. The muscle that showed activity most closely related to tremulous
      jaw movements was the temporalis. During bursts of jaw movements, temporalis
      muscles across several different rats showed bursts of EMG activity. Sections of
      videotape corresponding to bursts of EMG activity were reanalyzed by freeze-frame
      examination of the tape; typically, the temporalis showed a burst for each jaw
      movement, with the burst of activity occurring during the jaw-closing phase and
      the transition between jaw closing and opening. These results indicate that the
      local frequency of tremulous jaw movements is within the 3- to 7-Hz frequency
      that is typically associated with parkinsonian tremor. Moreover, the EMG data
      suggest that temporalis is a major contributor to the muscle activity that
      underlies tremulous jaw movements.

PMID- 9662080
TI  - Effects of methysergide and loratadine on food intake, mood, and performance of
      humans living in a residential laboratory.
AB  - The effects of loratadine, a peripherally acting histamine (H1) antagonist, and
      methysergide, a serotonin (5-HT) antagonist, were evaluated in seven normal
      weight, male research volunteers, participating in a placebo-controlled, double
      blind, 17-day residential study. Participants received oral loratadine (10 or 20
      mg), methysergide (4 or 8 mg), or placebo at 1000 and 1700 hours daily. Active
      drug was administered on Days 4, 5, 7, 8, 11, 12, 15, and 16; placebo was
      administered on all other days. Drug and dose order were counterbalanced across
      participants. Food intake, performance, and subjective ratings were measured
      repeatedly throughout the day. Loratadine had no effect on food intake,
      performance, or subjective ratings. In contrast, total caloric intake
      significantly decreased from approximately 3500 kcal during placebo
      administration to 3065 kcal on the first but not the second day of methysergide
      administration. Consumption of carbohydrate (p < 0.055), protein, and fat
      decreased on the first day of methysergide administration. This decrease in food
      intake was due to a decrease in meal size; the number of meals consumed was not
      affected. The proportion of calories derived from carbohydrates significantly
      increased on the first day of methysergide administration. Methysergide also
      significantly impaired performance of a psychomotor task on the first day of high
      dose administration and increased ratings of several subjective measures,
      including "Vomiting," "Stomach Pain," and "Miserable." These results suggest that
      the anorectic effect occurred as a result of the somatic and mood changes
      produced by methysergide. In addition, the inability of loratadine to affect food
      intake indicates that antagonism of central histamine receptors may be
      responsible for the increases in food intake produced by other antihistamines
      (e.g., diphenhydramine).

PMID- 9662081
TI  - Daily patterns of running wheel activity in male anophthalmic mice.
AB  - Circadian rhythms are generated by the suprachiasmatic nuclei (SCN) and
      synchronized (entrained) to environmental light-dark cycles by the
      retinohypothalamic tract (RHT), a direct pathway from the retina to the
      suprachiasmatic nuclei. In anophthalmic mice, the optic primordia are resorbed
      between embryonic days 11.5 and 13, before retinal ganglion cells emerge. Thus
      the retinohypothalamic tract, which is the primary "zeitgeber" for circadian
      rhythms in sighted animals, never forms, and there is no retinal or photic input
      to the circadian system. We have used wheel running activity, a highly consistent
      and reliable measure of circadian rhythmicity in rodents, to establish the
      properties of endogenous locomotor rhythms of anophthalmic mice. We have
      identified three subpopulations of anophthalmic mice: a) rhythmic with strong
      stable circadian period but significantly increased period length; b) rhythmic
      with unstable circadian period; and c) arrhythmic. Future correlation of
      locomotor rhythms with properties of the suprachiasmatic nuclei in these mice
      will clarify the relationship between generation and properties of circadian
      rhythms and the neuroanatomical, neurochemical, and molecular organization of the
      circadian clock.

PMID- 9662082
TI  - Developmental sodium restriction and gustatory afferent terminal field
      organization in the parabrachial nucleus.
AB  - Dietary sodium restriction instituted early in prenatal development produces
      physiological, anatomical, and functional changes in the gustatory system. For
      example, a rearrangement of the chorda tympani nerve terminal field within the
      nucleus of the solitary tract (NST) is observed in rats sodium restricted during
      development. The altered pattern of the chorda tympani nerve innervation within
      the nucleus of the solitary tract remains even after dietary sodium is restored
      in the diet at adulthood. In light of these observations, the terminal fields of
      second-order projections from the nucleus of the solitary tract to the
      parabrachial nucleus (PBn) were examined. To determine the possible
      rearrangements of the second-order projections, the rostral pole of the NST in
      control, restricted, and repleted rats was injected with the fluorescent tracer
      Fluoro-Ruby and the terminal fields in the parabrachial nucleus were analyzed.
      Results show no differences in the size or topography of the parabrachial nucleus
      terminal field among control, restricted, and repleted rats. These results
      suggest that the terminal field of second-order gustatory neurons is resistant to
      dietary sodium restriction during development. The apparent target-dependent
      effects may relate to differences in the developmental processes along the
      gustatory pathway.

PMID- 9662083
TI  - Effect of olivocochlear bundle lesion on locomotor activity in rats.
AB  - This study was conducted to investigate the effect of olivocochlear bundle (OCB)
      lesion on spontaneous locomotor activity in Wistar rats. The OCB is an auditory
      efferent pathway which originates from the superior olivary complex in the
      brainstem and terminates within the cochlea. It has an inhibitory effect on the
      auditory end organs. In the present study, the OCB was damaged at the floor of
      the fourth ventricle using radiofrequency current. The rats' locomotor activities
      were then monitored weekly for 2 months using an automated Digiscan activity
      monitor system. Six behavioral variables were collected and analyzed: horizontal
      activity (HA), total distance (TD), movement time (MT), vertical activity (VA),
      stereotypy count (SC), and margin time (MGT). Significant time-dependent
      increases were noted for HA, TD, VA, and SC following OCB lesion. These results
      of increasing exploratory and stereotyped behaviors may be caused by the rat
      experiencing more auditory stimulation than before due to OCB dysfunction and may
      cause the rat to become more curious to explore its surroundings.

PMID- 9662084
TI  - Release of a substance that suppresses spontaneous motor activity in the brain by
      physical exercise.
AB  - Injection of the cerebrospinal fluid (CSF) collected from rats fatigued by
      obligatory swimming into the cisterna magna of mice suppressed the spontaneous
      motor activity of the mice. The suppressive activity was abolished by heat
      denaturation of the CSF and was found in the CSF fraction with a molecular weight
      above 10,000 after ultrafiltration. These findings suggest the presence of a
      substance(s) released in a fatigued animal's brain that suppresses its
      spontaneous motor activity and generates the sensation of fatigue.

PMID- 9662085
TI  - Leptin (ob) mRNA and hypothalamic NPY in food-deprived/refed Syrian hamsters.
AB  - Food deprivation in the laboratory rat decreases plasma leptin and insulin,
      elevates glucocorticoid concentration, and increases the activity of the
      neuropeptide Y (NPY) system and feeding drive. In contrast, Syrian hamsters fail
      to modify feeding behaviour in response to various food scarcity paradigms. Two
      components of the neuroendocrine-hormonal response to food deprivation, adipose
      tissue-derived leptin and hypothalamic NPY, are investigated in the Syrian
      hamster. ob (leptin) mRNA was less abundant in subcutaneous than abdominal
      adipose tissue, but not to the extent observed in other rodents. Food deprivation
      for 48 h reduced ob mRNA in inguinal and retroperitoneal white adipose tissue;
      gene expression was partially restored by refeeding. In contrast, in epididymal
      fat there was no effect on ob mRNA. NPY concentrations in hypothalamic nuclei
      were also unaffected by feeding state. The predicted amino acid sequence of
      leptin from the Syrian hamster was over 90% homologous with Djungarian hamster
      and mouse sequences, and the leptin receptor gene (OB-R), and specifically the
      long intracellular splice variant, OB-Rb, was expressed in the same forebrain and
      hypothalamic regions that have been described in laboratory mice and rats,
      including hypothalamic arcuate, dorsomedial, and ventromedial nuclei. The failure
      of food deprivation to affect NPY and feeding behaviour in Syrian hamsters is
      unlikely to be due to defects in the leptin system, although there may be region
      specific differences in the regulation of leptin signaling in laboratory rats and
      Syrian hamsters.

PMID- 9662086
TI  - Gamma-hydroxybutyric acid intake in ethanol-preferring sP and -nonpreferring sNP
      rats.
AB  - Gamma-hydroxybutyric acid (GHB) and ethanol share several pharmacological
      similarities, suggesting that GHB may exert ethanol-like effects in the central
      nervous system. The present study was designed to test whether selectively bred
      ethanol-preferring rats would, unlike ethanol-nonpreferring ones, self-administer
      GHB, consistent with their higher preference for ethanol. Male ethanol-naive
      Sardinian alcohol-preferring (sP) and Sardinian alcohol-nonpreferring (sNP) rats
      were used. In Experiment 1, GHB solution (1% (w/v) in water) was initially
      offered as the sole fluid available for 14 consecutive days and then presented
      under the two-bottle, free-choice regimen, one bottle containing water and the
      other the GHB solution, for an additional 14 consecutive days. During the free
      choice phase, high preference for GHB and intake of pharmacologically relevant
      daily doses of GHB developed in both rat lines, presumably because the 14-day no
      choice period would unmask the reinforcing properties of GHB and lead to
      acquisition of GHB preference also in the supposedly less susceptible sNP rats.
      In Experiment 2, the forced GHB drinking phase was reduced to 3 days. Under the
      subsequent free-choice regimen, daily GHB preference and intake were initially
      low in both sP and sNP rats; however, after approximately 10 days, GHB preference
      and intake in sP rats rose progressively and then stabilized to significantly
      higher levels than in sNP rats throughout the entire free-choice phase. It is
      likely that episodic binges of GHB intake occurring during the first 10 days
      resulted in experiencing the reinforcing properties of GHB by sP but not sNP
      rats. The results of the present study suggest that a) sP rats are genetically
      more sensitive to the reinforcing effects of both ethanol and GHB than sNP rats;
      and b) disclosure of the higher sensitivity of sP rats to the reinforcing effects
      of GHB is a function of the length of the induction procedure. The results are
      also discussed in terms of differences in GHB receptors contributing to the
      predisposition to ethanol preference and avoidance, respectively.

PMID- 9662087
TI  - Detection of object orientation and spatial changes by mice: importance of local
      views.
AB  - This study examines the types of information used by mice to detect changes in
      their environment. After a period of habituation to an open field containing
      three bicolored cube-shaped objects, we modified the spatial configuration of the
      objects or rotated the objects 180 degrees, or both. We noted that whatever the
      modification, mice reexplored the objects. This shows that mice are able to
      detect both topological changes and, in particular, changes in the orientation of
      objects. This is possible only if mice can establish a local view of the objects
      in relation to a stable element of their environment. A second experiment showed
      that this stable element is in fact a pattern within the open field and not an
      element of the distal environment. These two experiments demonstrate the
      importance of local views in spatial representation for rodents.

PMID- 9662088
TI  - Intraspecific variation in the induction of female sexual receptivity in prairie
      voles.
AB  - Prairie voles (Microtus ochrogaster) are monogamous New World rodents which show
      geographic variation in social behavior. In this study, parameters of female
      reproduction which might be related to mating system were compared in prairie
      voles from eastern Kansas (KAN) versus central Illinois (ILL). KAN females showed
      a more rapid onset of natural estrus following exposure to a male and were more
      likely to respond to injections of a low dose (0.5 microg) of exogenous estradiol
      benzoate than ILL females. Neither mating duration nor pregnancy success after
      mate removal differed in KAN versus ILL females. These results suggest that ILL
      voles are less sensitive than KAN voles to the estrus-inducing effects of either
      endogenous or exogenous estrogen, supporting the hypothesis that variations in
      reproductive strategy occur among geographically discrete populations of prairie
      voles.

PMID- 9662089
TI  - Dyspnea in advanced chronic obstructive pulmonary disease.

PMID- 9662090
TI  - Significance of reverse transcription polymerase chain reaction in the detection
      of human cytomegalovirus gene transcripts in thoracic organ transplant
      recipients.
AB  - BACKGROUND: Cytomegalovirus disease is a major cause of morbidity in transplant
      recipients. We have evaluated the clinical value of detecting viral mRNA
      transcripts for the diagnosis of active infection leading to disease in
      recipients of thoracic organ transplants. METHODS: Blood samples from 10
      transplant recipients were analyzed before transplantation and weekly after
      transplantation for 12 weeks. The profile of viral immediate-early, early, and
      late gene expression was determined by the reverse transcription polymerase chain
      reaction and compared with cytomegalovirus (pp65) antigenemia and host antibody
      status (serologic study). RESULTS: Two patients showed no active cytomegalovirus
      infection, one had asymptomatic infection detected serologically and seven
      patients had development of symptomatic infection with a significant serologic
      change. Viral immediate-early mRNA transcript was detectable in all 10 patients,
      including the two with no active infection. Early and late gene expression
      occurred in seven patients who were all antigenemia positive and in whom disease
      developed. Of the seven patients with development of antigenemia, six showed
      viral early and late gene expression before pp65 antigenemia, whereas one patient
      showed antigenemia before early and late gene expression. CONCLUSION: We have
      shown that the detection of viral early and late gene expression by reverse
      transcription polymerase chain reaction can act as diagnostic markers of
      cytomegalovirus disease with expression of early gene preceding the detection of
      antigenemia in most cases. In contrast, viral immediate early gene expression did
      not correlate with clinical infection. This diagnostic approach could be useful
      in the treatment of thoracic organ transplant recipients.

PMID- 9662091
TI  - Expression of proliferating cell nuclear antigen in bronchial epithelium after
      lung transplantation in the rat.
AB  - BACKGROUND: The normal, mature airway epithelium in experimental animals has a
      very slow cell turnover and minimal proliferation. The aim of this study was to
      investigate the expression of proliferating cell nuclear antigen (PCNA) as an
      index of bronchial cell proliferation in the Brown Norway to Lewis rat pulmonary
      allograft model with or without immunosuppression. METHODS: Brown Norway left
      lungs were transplanted into Lewis recipients. Some recipients were treated with
      a high dose of cyclosporine and FK506. Lewis-to-Lewis donor-recipient combination
      was performed as a control. Lungs were excised on postoperative days 3 and 5.
      Routinely processed, paraffin-embedded sections were prepared and stained by
      PCNA. Counts of PCNA-positive cells in the perivascular cellular infiltrate and
      bronchial surface epithelium were compared with the histologic grade of
      rejection. RESULTS: The PCNA index (percent of nuclei immunostaining for PCNA) in
      bronchial surface epithelium was significantly higher in allografts (21.0% +/-
      3.1% at 3 days, 31.4% +/- 9.8 % at 5 days, p < 0.05) than in isografts (5.4% +/-
      3.0% at 3 days, 4.7% +/- 4.6% at 5 days). The PCNA index was also greater in the
      perivascular infiltrates of rejecting lungs (23.9% +/- 3.7% at 3 days, 29.1% +/-
      6.6% at 5 days). However, in the cyclosporine- and FK506-treated groups, the PCNA
      index in bronchial surface epithelium was suppressed to less than 5% at 3 and 5
      days. Even at 50 days after transplantation, PCNA-positive cells were rare in
      bronchial epithelium of FK506-treated grafts. CONCLUSIONS: Bronchial epithelium
      in isografts has a relatively low rate of proliferation. In rejection, allografts
      have a very rapid cell turnover and proliferation. Proliferating epithelium may
      be a consequence of immune events or it may contribute to the pathogenesis of
      those events.

PMID- 9662092
TI  - Inhaled nitric oxide does not increase rat pulmonary allograft rejection.
AB  - BACKGROUND: There is evidence that inducible nitric oxide (NO) may be directly
      related to the process of allograft rejection. Because of its strong pulmonary
      vasodilatory activity, inhaled NO (INO) has recently been used as a therapeutic
      option for allograft dysfunction after lung transplantation. The action of
      inducible NO and inhaled NO seems contradictory for preserving
      posttransplantation pulmonary allograft function. INO used for lung transplant
      recipients may actually enhance acute allograft rejection. We studied the effect
      of INO on acute allograft rejection with a rat pulmonary allograft model. METHOD:
      A total of 24 left lung allotransplantations were performed from Lewis donors
      into F344 recipients. Animals were divided into two groups and inhaled either
      room air alone or 20 ppm NO with room air in a closed chamber immediately after
      transplantation until rats were killed on days 7 and 14. During observation, NO
      uptake was monitored by measuring serum NO2-/NO3- level. Acute rejection was
      evaluated by use of a semiquantitative radiographic scoring method (aeration
      score: 0 to 6, opaque to normal appearance) and rejection score (0 to 4, no sign
      of rejection to diffuse mononuclear infiltration). RESULTS: Markedly elevated
      serum NO2-/NO3- levels were observed in the NO inhalation group compared with
      levels in the normal air inhalation control group (110.8 +/- 25.3 vs 16.3 +/- 4.0
      micromol/L/ml on day 7, p < 0.01; 107.0 +/- 30.9 vs 16.8 +/- 4.8 micromol/L/ml on
      day 14, p < 0.01). However, no positive effect of INO on acute rejection was
      found histologically or radiographically. CONCLUSION: The effect of INO on acute
      rejection is likely so minimal as not to be clinically relevant.

PMID- 9662093
TI  - Detecting acute graft rejection in patients after orthotopic heart
      transplantation: analysis of heart rate variability in the frequency domain.
AB  - BACKGROUND: Acute transplant rejection is a major complication after heart
      transplantation. To treat patients with rejection, early detection is necessary
      before fatal heart dysfunction. Because of its invasive aspect, endomyocardial
      biopsy is limited with respect to its frequency and complication rate. Little
      work has been done so far to develop noninvasive methods for detecting rejection,
      and, hence, investigation for such methods would seem to be of considerable
      value. METHODS: After routine endomyocardial biopsy in 117 heart transplant
      recipients (age 49 +/- 13 years time after transplantation 6 to 48 months),
      electrocardiography results were recorded with the patient in a supine position
      at a controlled respiratory rate (0.25 Hz) over 10 minutes. Patients with an
      artificial pacemaker or severe arrhythmia were excluded. On the basis of
      endomyocardial biopsy reports, two groups of patients were defined: patients
      without rejection (AR0, n = 73) and patients with severe rejection (AR1b to AR4,
      n = 32). The spectra of R-wave to R-wave intervals were calculated, and different
      spectral components were evaluated: low frequency (LF, 0.05 to 0.18 Hz), high
      frequency (HF, 0.18 to 0.5 Hz), LF + HF, LF + HF minus the respiratory peak (RP)
      (LF + HF - RP), and the total power (0 to 0.5 Hz). RESULTS: All frequency domain
      parameters except HF were significantly higher in patients with severe rejection
      than in patients without rejection. By means of the calculation of receiver
      operating characteristic curves, LF + HF - RP was the most reliable frequency
      domain parameter for the detection of severe rejection. Setting its threshold
      value to 5 msec2, 77% sensitivity, and 76% specificity could be achieved.
      CONCLUSIONS: Spectral analysis of heart rate variability may be used as a
      noninvasive tool to detect severe rejection episodes.

PMID- 9662094
TI  - Squamous and basal cell carcinoma in heart transplant recipients.
AB  - BACKGROUND: Cutaneous malignancies are frequent in organ transplant recipients.
      We retrospectively reviewed a large series of heart transplant recipients and
      report on the prevalence and risk factors for development of cutaneous squamous
      and basal cell carcinoma. METHODS: Between Dec. 4, 1985, and Dec. 27, 1996, 299
      heart transplantations were performed at the Oregon Health Sciences University.
      Heart transplant recipients with more than 6 months survival or follow-up were
      investigated for squamous and basal cell carcinoma (n = 248). RESULTS: Forty-one
      patients (17%) were found to have 192 squamous or basal cell carcinomas. Squamous
      cell carcinoma was the predominate skin malignancy, constituting 172 (90%) of the
      lesions. The mean number of skin malignancies per patient was 4.7 +/- 0.81 (range
      125). Patients with development of a skin malignancy were 8 years older on
      average, with a male-to-female ratio of 19.5:1. The predominant skin type and eye
      color were fair (59%) and blue (59%), respectively. Cumulative risk, based on
      actuarial survival analysis for development of a squamous or basal cell carcinoma
      at 1 year, was 3% and increased to 21% and 35% at 5 and 10 years, respectively.
      In addition, cumulative risk increased in patients who received treatment with
      OKT3. CONCLUSION: Cumulative risk of development of a skin malignancy increased
      with time and use of OKT3. Additional patient risk factors included older age,
      male sex, fair skin, and blue eyes.

PMID- 9662095
TI  - Adjuvant treatment with ursodeoxycholic acid may reduce the incidence of acute
      cardiac allograft rejection.
AB  - BACKGROUND: The nontoxic bile acid, ursodeoxycholic acid (UDCA), is an effective
      drug for the treatment of different cholestatic conditions. Furthermore, an
      immunomodulatory capacity of UDCA has been reported in vitro, as well as in vivo,
      in different immune-mediated liver diseases and after liver transplantation.
      METHODS: In this retrospective study, the influence of UDCA on heart transplant
      rejection was investigated in 21 cardiac allograft recipients receiving UDCA for
      cyclosporine-induced cholestasis (500 mg administered twice daily, start of
      therapy within the first postoperative month, duration >8 weeks). Thirty-one
      patients not receiving UDCA served as control subjects. All patients received
      triple-maintenance immunosuppression (cyclosporine, azathioprine, prednisolone).
      For quantitative comparison of rejection severity, the following score was
      applied: 0, no specific therapy; 1, temporary increase in oral steroids; 2,
      intravenous steroids; 3, ATG or OKT3 therapy. RESULTS: During the first 6
      postoperative months, the number of acute rejection episodes requiring specific
      anti-rejection therapy was significantly lower in the UDCA group as compared with
      control subjects (1.38 +/- 1.36 vs 2.74 +/- 1.83 rejection episodes per patient,
      p = 0.005). The cumulative score was significantly lower in the UDCA group as
      compared with control subjects (2.38 +/- 2.29 vs 5.06 +/- 3.61, p = 0.004).
      CONCLUSIONS: These initial data indicate a beneficial effect of adjuvant UDCA
      treatment in the early phase after heart transplantation probably related to
      immunomodulating properties of UDCA, which may be used therapeutically after
      organ transplantation.

PMID- 9662096
TI  - Optimal inflation volume for hypothermic preservation of rat lungs.
AB  - BACKGROUND: Recent studies have suggested that preservation of donor lungs with
      inflation provides better pulmonary function after transplantation, but
      hyperinflation of pulmonary grafts during storage increases reperfusion pulmonary
      edema. To elucidate the optimal inflation volume during the preservation period,
      and the possible role of barotrauma in lung injury after atelectatic storage, we
      examined the effects of inflation volume and reinflation protocols in
      hypothermically preserved rat lungs. METHODS: Adult rat lung blocks were
      preserved at 4 degrees C for 18 hours at various levels of inflation. Static
      pulmonary compliance was measured and compared before and after preservation. The
      hemodynamics and gas exchange function of optimally inflated lungs were then
      compared with lungs preserved atelectatically in a rat paracorporeal reperfusion
      model. RESULTS: We found that the optimal level of inflation for preservation is
      50% of total lung capacity (TLC). Lungs stored atelectatically or inflated to 25%
      of TLC showed deterioration of postpreservation lung compliance, whereas air
      leaks were observed in most of the lungs preserved with inflation to 75% or 100%
      of TLC. The hemodynamics and gas exchange function in lungs preserved with
      inflation at 50% of TLC were significantly better than that of atelectatically
      preserved lungs. A gentle reexpansion of atelectatically stored lungs did not
      prevent the deterioration of pulmonary function. CONCLUSION: Donor lungs should
      be preserved at an optimal inflation volume, and mechanisms other than barotrauma
      after atelectatic storage may be responsible for postpreservation and
      postreperfusion lung injury.

PMID- 9662097
TI  - Effect of improved myocardial protection on edema and diastolic properties of the
      rat left ventricle during acute allograft rejection.
AB  - BACKGROUND: Studies of myocardial edema and diastolic dysfunction in rat heart
      transplantation have been flawed by ischemic injury. This study uses improved
      methods to prevent ischemic contracture. METHODS: Hearts of 30 ACI rats were
      transplanted into the abdomen of Lewis rats by use of cold University of
      Wisconsin solution for improved preservation. Left ventricular diastolic
      properties were expressed as volume at standardized pressure intervals. RESULTS:
      On posttransplantation day 3, mean left ventricular volume at 15 mm Hg in
      allografts (290 +/- 9 microl, SEM) was not significantly different vs isografts
      (299 +/- 32 microl), allografts on day 0 (337 +/- 28 ml) or day 1 (324 +/- 20
      microl), or native hearts (334 +/- 19 microl). However, volume was reduced to 173
      +/- 17 microl on day 4 and to 70 +/- 23 microl on day 5 (p < 0.05). Similar
      findings were obtained for volume at 5 and 10 mm Hg. Allograft myocardial water
      content on day 3, 76.3% +/- 5%, similar to allografts on day 0 and 1 and to
      isografts on day 3, increased to 77.6% +/- 8% on day 4 (NS) and 79.4% +/- 6% on
      day 5 (p < 0.05 vs day 0). Histologically, rejection in allografts was mild on
      day 3, moderate on day 4, and severe on day 5. CONCLUSIONS: Reduced left
      ventricular filling volume during rejection is only partially explained by edema.
      Abnormalities of diastolic properties previously attributed to the unloaded state
      of nonworking heart models may actually reflect inadequate peritransplantation
      myocardial protection.

PMID- 9662098
TI  - Vasoactive intestinal peptide ameliorates reperfusion injury in rat lung
      transplantation.
AB  - BACKGROUND: Vasoactive intestinal peptide (VIP) has been reported to have some
      properties that provide protection from lung injury. Furthermore, its protective
      effect in cold storage of donor lungs has been confirmed. We examined its effect
      and the timing of administration in an in vivo rat lung transplantation model.
      METHODS: All lungs were flushed with low-potassium dextran-1% glucose solution,
      and orthotopic left lung transplantations were performed. Rats were divided into
      four groups (n = 6). Group I received no preservation or storage. Groups II, III,
      and IV grafts were stored for 18 hours at 4 degrees C. Group II received no VIP.
      Group III received VIP (0.1 g/ml) via the flush solution. Group IV recipients
      received VIP (3 microg/kg) intravenously just after reperfusion. Twenty-four
      hours after transplantation, the right main pulmonary artery and right main
      bronchus were ligated, and the rats were ventilated with 100% O2 for 5 minutes.
      Mean pulmonary arterial pressure, peak airway pressure, blood gas analysis, serum
      lipid peroxide level, tissue myeloperoxidase activity, and wet-dry weight ratio
      were measured. RESULTS: The partial O2 tension values of groups III and IV were
      better than group II (groups II, III, and IV: 147.4 +/- 71.4, 402.1 +/- 64.8,
      373.4 +/- 81.0 mm Hg; p < 0.05). Peak airway pressure was lower in groups III and
      IV than in group II (groups II, III, and IV: 19.7 +/- 0.8, 16.7 +/- 0.9. and 16.3
      +/- 1.0 mm Hg; p < 0.05). Mean pulmonary arterial pressure in group III was lower
      than group II (groups II and III: 36.3 +/- 3.0 and 22.1 +/- 2.2 mm Hg; p < 0.01).
      Wet-dry weight ratio in group III was lower than in groups II and IV (group II,
      III, and IV: 5.2 +/- 0.2, 4.4 +/- 0.2, and 5.2 +/- 0.3; II vs III; p < 0.05, III
      vs IV; p < 0.01). Serum lipid peroxide levels in groups III and IV were
      significantly lower (groups II, III, and IV: 2.643 +/- 0.913, 0.455 +/- 0.147,
      and 0.325 +/- 0.124 nmol/ml; p < 0.01). CONCLUSION: VIP ameliorates reperfusion
      injury in an in vivo rat lung transplantation model. Either administration of VIP
      via the flush solution or systemically just after reperfusion was associated with
      improved pulmonary function.

PMID- 9662099
TI  - Delayed administration of low-dose NPC18915 ameliorates lung ischemia-reperfusion
      injury.
AB  - BACKGROUND: NPC18915, a member of new antiinflammatory agent called nactins
      (neutrophil activation inhibitors), has been shown to reduce reperfusion injury
      in rat lung transplantation at high dosage. In vitro studies have demonstrated
      effectiveness of this compound even at low dosage. We hypothesized that this
      compound ameliorates lung ischemia reperfusion injury even at low dosage levels
      if administration is optimally timed. The aim of this study was to determine the
      efficacy and the best timing for administration of low-dose NPC18915. METHODS:
      Forty syngeneic rat left lung transplantations were performed. All isografts were
      flushed with low-potassium dextran-1% glucose solution 20 ml and preserved for 18
      hours at 4 degrees C. Animals were divided into four groups. Group I animals (n =
      10) served as control subjects. In groups II (n = 10), III (n = 10), and IV (n =
      10), NPC18915 (0.04 mg) was added to the flush solution and was administered
      intravenously (0.4 mg/kg) immediately before reperfusion (group II) and 60
      minutes (group III) and 120 minutes (group IV) after reperfusion. Pulmonary
      function was assessed 24 hours after reperfusion. RESULTS: In group III,
      oxygenation improved in comparison to group I (247.2 +/- 59.8 versus 76.6 +/-
      16.0 mm Hg, p < 0.002). Wet-to-dry weight ratio and graft myeloperoxidase
      activity were significantly improved (group III versus group I, 6.02 +/- 0.21
      versus 7.19 +/- 0.41, p = 0.013) (group III versus group I, 0.093 +/- 0.019
      versus 0.207 +/- 0.023 delta optical density/min/mg, p < 0.002). There were no
      significant differences in CD11b expression. CONCLUSION: These data suggest that
      delayed administration of NPC18915, 60 minutes after reperfusion, dramatically
      improves pulmonary graft function.

PMID- 9662100
TI  - Minimally invasive direct coronary artery bypass grafting without cardiopulmonary
      bypass in combination with intraoperative percutaneous transluminal coronary
      angioplasty for palliative coronary revascularization in a heart transplant
      recipient.
AB  - The use of minimally invasive direct coronary artery bypass grafting without
      cardiopulmonary bypass in combination with intraoperative percutaneous
      transluminal coronary angioplasty for myocardial revascularization in a heart
      transplant recipient is reported.

PMID- 9662101
TI  - Heart and lung retransplantation: should it be done?

PMID- 9662102
TI  - SIDS redux: is it or isn't it?

PMID- 9662103
TI  - Acceleration-deceleration injuries to the brain in blunt force trauma.
AB  - Blunt force trauma to the stationary head is generally associated with cortical
      subcortical injuries located at the site of impact (i.e., coup contusions). We
      present 2 cases of cerebral contusion injury secondary to falling tree limbs
      hitting the head, illustrating an exception to this observation. In each case,
      the most prominent lesions were white matter hemorrhagic contusions similar to
      those associated with acceleration-deceleration types of injuries characterizing
      falls or motor vehicle accidents (i.e., contrecoup contusions). The proposed
      pathogenesis for these observed lesions is a forceful impact resulting in the
      acceleration of the head and brain of a magnitude comparable with that in a motor
      vehicle accident or a fall.

PMID- 9662104
TI  - Toward a broader definition of heat-related death: comparison of mortality
      estimates from medical examiners' classification with those from total death
      differentials during the July 1995 heat wave in Chicago, Illinois.
AB  - The classification of heat-related deaths solely according to body temperatures
      underestimates the magnitude of heat-related mortality during heat waves. Broader
      classifications are often used, but their utility in defining the mortality and
      identifying at-risk populations has not been evaluated. Using death data from the
      July 1995 heat wave in Chicago, the authors compared heat-related mortality rates
      based on the classification of heat-related deaths by the Cook County Medical
      Examiner's Office (CCMEO), with excess mortality rates based on total mortality
      differentials during and before the heat wave. In July 1995, the overall
      mortality in Chicago was 19 deaths per 100,000 population for heat-related
      mortality and 24 to 26 deaths per 100,000 population for excess mortality. Across
      Chicago community areas, the two mortality rates were closely related (r = 0.73
      0.79; p < .01), but heat-related mortality rates were lower than excess mortality
      rates in community areas where excess mortality rates were higher (slope < 1; p <
      .01), a finding indicating an underestimation of heat-related deaths in such
      areas. The underestimation could not be explained by uncertainties in estimating
      excess mortality rates or by differences in socioeconomic and demographic
      characteristics among communities. These results support using the broader CCMEO
      classification of heat-related deaths as a relative indicator to target
      communities for prevention and relief efforts, but not as an adequate measure of
      actual heat-related mortality in a high-risk neighborhood.

PMID- 9662105
TI  - Sudden death in an adolescent boy due to a colloid cyst of the third ventricle.
AB  - A 13-year-old boy died suddenly at night while asleep. A colloid cyst filled the
      third ventricle, obstructed the flow of cerebral spinal fluid, and led to
      prominent hydrocephalus. Acute ventricular distension with brain herniation
      resulted in death, whereas repeated previous episodes had led to cerebral
      compression and edema. Complaints included only episodic headache in the month
      prior to death. His pediatrician prescribed a course of Imitrex (sumatriptan)
      because of lack of neurologic signs or other symptoms and a family history of
      migraine headaches. The headaches persisted, however, and within 1 month the
      patient died. The difficulty of accurate clinical diagnosis in this case is
      common. Subtle signs or even lack of symptoms of increased intracranial pressure
      may prevent a timely diagnosis before the occurrence of deadly complications.
      This case report helps to remind both forensic medical examiners and clinicians
      that this entity, although rare, should remain in the differential diagnosis of
      headache in children and young adults and of hydrocephalus at autopsy. Timely
      diagnosis of this benign lesion can lead to a surgical cure.

PMID- 9662106
TI  - Distribution of biochemical markers in biologic fluids: application to the
      postmortem diagnosis of myocardial infarction.
AB  - We evaluated the usefulness of postmortem determination of biochemical markers
      and the ratio of their concentrations in pericardial fluid and serum to diagnose
      acute myocardial necrosis. One hundred cadavers from routine necropsies were
      studied. Cases were allocated in diagnostic groups according to the cause of
      death. Myoglobin and myosin heavy chain concentrations and creatine kinase MB
      isoenzymes (CK-MB) activities were measured in serum and pericardial fluid.
      Ratios of the concentrations obtained in these fluids were calculated.
      Hematoxylin and eosin (H&E) and acridine orange stains were used for microscopy
      studies. Pericardial fluid-serum ratios of the concentrations of biochemical
      markers were significantly different. The ratio of the concentrations of myosin
      is the best indicator of wide-spread muscle damage or cardiac necrosis.

PMID- 9662107
TI  - Immunohistochemical indicators of early brain injury: an experimental study using
      the fluid-percussion model in cats.
AB  - To detect early changes in neurons and astrocytes by immunohistochemical methods
      using antibodies against the neuron-specific enolase (NSE), neurofilament, glial
      fibrillary acid protein (GFAP), and S-100 protein, a fluid-percussion injury
      model in cats was chosen, in which a severe grade of injury (3.5-5.5 atm) was
      produced. Neuropathologic changes were produced through brain deformation by
      pressure gradients at the time of injury. The neuronal NSE immunoreactivity in
      the parietal cortex and the brain stem began to decrease at 1 to 2 hours after
      injury and were reduced markedly or even lost 4 hours after injury. Axons in the
      cerebral white matter and corpus callosum and in the hemorrhage regions at the
      brain stem were waved and enlarged <4 hours after injury. From 4 hours after
      injury, retraction balls were found after staining by antibody for the
      neurofilament. The GFAP-positive astrocytes appeared in the impact site in the
      parietal cortex and in the brain stem from 4 hours after injury, whereas S-100
      positive astrocytes were not markedly changed, indicating that early after the
      injury, astrocytes manifested reactive hypertrophy without proliferation. These
      results suggest that immunochemical studies on NSE, neurofilament, GFAP, and S
      100 are useful in pathologic and forensic practice in a patient who survives for
      a short time after a fatal head injury but without obvious focal damage.

PMID- 9662108
TI  - Fatal anaphylaxis due to fire ant stings.
AB  - Imported fire ants (Solenopsis invicta and Solenopsis richteri) are the source of
      a potentially lethal environmental hazard in the southeastern United States.
      Because of their resistance to natural and chemical control, fire ants can
      overwhelm their environment, causing destruction of land and animals. Fire ants
      can also cause a variety of health problems in humans, ranging from simple stings
      to anaphylaxis and death. We present a case of a 30-year-old woman who died of
      anaphylaxis following multiple fire ant stings. At autopsy, multiple skin lesions
      characteristic of those produced by fire ant stings were present on her arm.
      Postmortem blood samples were positive for imported fire ant venom-specific IgE
      antibodies (5654 ng/ml) and tryptase (12 ng/ml). Deaths caused by imported fire
      ant stings are rare but are likely to become more common as the fire ant
      population expands. In this report, we review deaths due to fire ant stings,
      discuss postmortem laboratory findings, and stress the importance of recognizing
      the characteristic skin lesions produced by fire ants.

PMID- 9662109
TI  - Diphenhydramine toxicity: comparisons of postmortem findings in diphenhydramine-,
      cocaine-, and heroin-related deaths.
AB  - Diphenhydramine (DPH)-related deaths in adults are extremely rare, and detailed
      autopsy studies are rarer still. Toxicologic and anatomic findings in 4 cases of
      suicidal DPH overdose are described and compared with findings in a database of
      cocaine- and heroin-related deaths. Blood DPH levels were many times higher than
      those considered therapeutic (5000-35,000 ng/ml versus 50-100 ng/ml). Marked
      pulmonary edema with visceral congestion was a constant finding. Mean lung-body
      weight ratios for DPH, cocaine, heroin, and trauma controls were 0.015, 0.015,
      0.019, and 0.013, respectively. When normalized for body weight in this fashion,
      edema in DPH-related deaths was comparable to that in cocaine-related deaths.
      Cardiac enlargement was apparent in 3 of the 4 DPH cases, 1 with marked
      myocardial fibrosis. The finding of increased heart size suggests that
      preexisting heart disease may provide the necessary substrate for lethal cases of
      DPH toxicity. Pulmonary edema in these cases remains unexplained, with edema in
      cases of heroin-related toxicity significantly worse than that produced by
      cocaine or DPH (p < .0001). Because DPH and cocaine can exert similar effects on
      the heart, a common mechanism may produce pulmonary edema in both. A different
      mechanism may account for heroin-related edema.

PMID- 9662110
TI  - Intentional overdose and death with 3,4-methylenedioxyethamphetamine (MDEA;
      "Eve"): case report.
AB  - We report a case of suicide following ingestion of a large dose of 3,4
      methylenedioxyethamphetamine (MDEA, "Eve") in a 27-year-old woman with a history
      of depression. Several days before her death, she had attempted suicide with
      benzodiazepines resulting in a 24-hour hospital admission; at that time, no
      physiologic abnormalities were detected. Findings on autopsy were nonspecific.
      Toxicologic analysis showed a high concentration of MDEA and the appearance of
      benzodiazepines in body fluids. Ethanol and other drugs of abuse were not found.
      We discuss the clinical manifestations, toxicologic syndromes, and mechanisms of
      death with amphetamine intoxication. MDEA intoxication in young people may result
      in sudden death.

PMID- 9662111
TI  - Soft tissue tumors following traumatic injury: two observations of interest for
      the medicolegal causality.
AB  - Two cases of tumors of the soft tissues developing at the site of a previous
      traumatic injury occurring a few years earlier are reported. One was finally
      diagnosed as aggressive fibromatosis and the other as low-grade fibrosarcoma.
      Among the pathogenic mechanisms and the etiologic factors involved in such
      tumors, the posttraumatic causality is discussed, and in addition to the initial
      trauma, the role of iterative surgery in the first case and mineral muscular
      inclusions in the second case are examined. The different therapeutic approaches
      of such lesions are also reviewed.

PMID- 9662112
TI  - Causes of sudden cardiac death in young athletes: the role of hypoperfusion.
AB  - The role of hypoperfusion in cases of sudden cardiac death of young athletes is
      discussed. The coronary index, a ratio of the coronary caliber and the myocardial
      mass, was estimated from postmortem coronary angiograms. The coronary index
      reflects the degree of myocardial blood supply. In each case, a decrease in the
      coronary index, in combination with fibrosis and necrosis of the myocardium, was
      revealed. We suggest that recurring myocardial necrosis developed as a result of
      hypoperfusion of the hypertrophic myocardium during physical overload.

PMID- 9662113
TI  - Sudden death due to obstruction of coronary artery ostium by aortic valve
      papillary fibroelastoma.
AB  - Papillary fibroelastomas are rare endocardial growths that most commonly occur on
      the cardiac valves. Whether papillary fibroelastomas represent true neoplasms,
      hamartomas, or degenerative changes is debatable. Whatever their origin,
      papillary fibroelastomas have a characteristic gross and microscopic appearance,
      are usually solitary, and are almost always incidental findings at autopsy or
      during cardiac surgery. We report a case of sudden death caused by occlusion of
      the right coronary artery ostium by a papillary fibroelastoma of the aortic
      valve. We discuss the gross and microscopic features, differential diagnosis, and
      etiology and pathogenesis of this rare and interesting cardiac lesion.

PMID- 9662114
TI  - Fatal upper esophageal hemorrhage caused by a previously ingested chicken bone:
      case report.
AB  - Perforation of the upper esophageal wall by ingested bones can cause sudden death
      and death under suspicious circumstances. Perforation usually takes place at
      sites of physiologic and pathologic strictures. Temporary bleeding from the
      respiratory and digestive tracts is an important signal and may be crucial in the
      diagnosis of esophageal perforation and small vessel injury by ingested bone.
      Polymorphism and long symptomatology can cause diagnostic and therapeutic
      failure, thus presenting a special medicolegal problem. We present a case report
      of unknown cause of death and death under suspicious circumstances resulting from
      ingested bone perforation of upper esophagus. A chicken bone had been swallowed
      about 6 months before death caused by hemorrhage from a decubitus in the cervical
      esophagus. The patient underwent urgent surgery because of suspected bleeding of
      a ventricular ulcer.

PMID- 9662115
TI  - Medicolegal aspects of the Thai Airbus crash near Kathmandu, Nepal: findings of
      the investigating pathologists.
AB  - A Thai Airbus, carrying 99 passengers and 14 crew members, traveling from Bangkok
      to Kathmandu, hit a mountain and crashed several minutes before landing. There
      were no survivors. Recovered human remains, none of which was easily
      identifiable, varied in size from a small piece of muscle to mutilated bodies. Of
      the 97 fragments, only 15 were sufficiently intact (albeit, only partially) to be
      designated as "bodies." Of the fragments and "bodies," only 11 were positively
      identified. Causes of death, although all traumatic, could not be stated
      accurately due to the degree of disintegration. Identification of human remains
      in these circumstances is a major problem for the pathologist.

PMID- 9662116
TI  - Sudden asphyxial death complicating infectious mononucleosis.
AB  - Infectious mononucleosis (IM) is a disease traditionally defined by a triad of
      clinical, laboratory, and serologic factors. It is typically a benign, self
      limited disease of children and young adults. Upper airway obstruction is a rare
      but potentially fatal complication of IM resulting from massive tonsillar
      enlargement, pharyngeal edema, or both. We report a case of sudden death due to
      airway obstruction in IM.

PMID- 9662117
TI  - Fatal automobile crash caused by cerebral toxoplasmosis.
AB  - An unusual case of cerebral toxoplasmosis leading to a fatal vehicular crash is
      presented. Massive intracerebral hemorrhage, a rare complication of cerebral
      toxoplasmosis in persons with acquired immunodeficiency syndrome (AIDS), caused
      sudden onset of increased intracranial pressure that led to loss of control of
      the vehicle and an ensuing fatal traffic crash.

PMID- 9662118
TI  - Dealing with the news media: effective communication strategies for medical
      examiners.
AB  - Medical examiners have responsibilities that often result in news media coverage
      that can bring unwanted attention. Dealing with the news media is always a
      learning process, but various resources exist to help in maintaining credibility.
      Local offices should consider establishing proactive community relations and
      media relations programs. Appropriate steps should be taken to manage media
      relations, including the appointment of an official spokesperson and regular use
      of the prepared statement. This article also explores the benefits of being
      prepared for media interviews, offers advice for responding to the media
      following a mass disaster, and examines options for dealing with a media
      investigation. Medical examiners, coroners, investigators, and other forensic
      experts have responsibilities that frequently bring them in contact with the news
      media. Today, a crime scene investigation is not complete without media
      attention. We now live in an era of "CNN journalism," in which local
      investigations may be propelled into the national spotlight. Unfortunately, the
      result can be unwanted attention. What resources can medical examiners rely on to
      better manage the news media? What can you do to maintain credibility? There are
      a number of options available, all of which can easily put into practice.

PMID- 9662119
TI  - A suicide disguised as a homicide: return to Thor Bridge.
AB  - Suicides staged as homicides are uncommon. We present a case of a self-inflicted
      gunshot wound of the chest disguised by the victim as a homicide, using a method
      described by Sir Arthur Conan Doyle in his Sherlock Holmes story, "The Problem of
      Thor Bridge."

PMID- 9662120
TI  - Death from electrocution during autoerotic practice: case report and review of
      the literature.
AB  - A fatal case of electrocution occurring during autoerotic practice is described.
      A plausible reconstruction of the accident involves attachment of one electrode
      to the anus and accidental touching of the other electrode with hand and chest
      when attempting to attach it to the penis. Death was caused by myocardial
      fibrillation. Both cable and pornographic literature were obviously hidden by the
      parents of the deceased to conceal the actual cause of death. The accident is
      compared to cases found in the literature.

PMID- 9662121
TI  - Planned complex suicide.

PMID- 9662122
TI  - Simultaneous death of twins: an environmental hazard or SIDS?

PMID- 9662123
TI  - Nitric oxide synthase expression in bone cells.
AB  - We have localized the expression of the three main nitric oxide synthases (eNOS,
      bNOS, and iNOS) in bone cells of rats and humans using immunohistochemistry. The
      predominant isoform expressed in normal adult bone was the constitutive isoform,
      eNOS, mainly in cells of osteoblastic lineage. In adult bone, the osteoblast
      lineage cells exhibiting eNOS expression were flat bone lining cells and
      osteocytes, but cuboidal osteoblasts were consistently negative. Expression for
      bNOS was not detected in any bone cells. iNOS expression was not detected in any
      cells of osteoblastic lineage in normal adult rat or human bone, but was observed
      in cuboidal osteoblasts of adult rats with experimental colitis, in which the
      suppression in bone formation may be cytokine mediated. Osteoclasts in normal rat
      tissue showed expression for both eNOS and iNOS, but these were patchy. As for
      cells of the osteoblast lineage, osteoclasts were negative for bNOS. Thus, our
      findings support evidence, from in vitro studies and from animal experiments,
      that nitric oxide may play an important role in the physiology of bone.

PMID- 9662124
TI  - Stromelysin-1 (MMP-3) and stromelysin-2 (MMP-10) expression in developing human
      bone: potential roles in skeletal development.
AB  - Stromelysin, a member of the matrix metalloproteinase family, demonstrates wide
      substrate specificity with the ability to degrade proteoglycan, fibronectin,
      laminin, casein, and the nonhelical region of collagen. The two forms of
      stromelysin (SL), types 1 (MMP-3) and 2 (MMP-10), share 82% sequence homology,
      but exhibit differences in cellular synthesis and inducibility by cytokines and
      growth factors in vitro. However, the distribution of the two isoforms in bone
      has not been reported. We investigated the presence of SL-1 and SL-2 in human
      osteophytic and neonatal rib bone using immunohistochemistry and, combined with a
      new method of in situ zymography, determined the activity of the immunolocalized
      stromelysins. Latent SL-1 was strongly expressed in the extracellular matrix in
      fibrous tissue surrounding areas of endochondral ossification in osteophytes, and
      adjacent to the periosteum of fetal rib bone. Active SL-1 expression was detected
      in osteocytes and the matrix surrounding osteocytic lacunae. SL-2 showed intense
      cell-associated staining at sites of resorption in areas of endochondral
      ossification and in resorptive cells at the chondro-osseous junction, which
      correlated with enzyme activity detected by zymography. Within the rib, active SL
      2 expression was localized in chondrocytes of the growth plate, whereas only
      occasional SL-1 signal was evident. Vascular areas showed strong SL-2 staining
      with some proteolytic activity. SL-2, but not SL-1, was strongly expressed in
      osteoclasts and most mononuclear cells within the marrow. At sites of bone
      formation both isoforms were expressed by osteoblasts with SL-1 also present in
      osteoid. These results demonstrate, for the first time, the differential
      expression of SL-1 and SL-2 in developing human bone, indicating specific roles
      for the two isoforms. In situ zymography demonstrates that SL-2 is produced in an
      active form with associated degradation, whereas SL-1, in a matrix-bound
      proenzyme form, may act as a reservoir for later activation.

PMID- 9662125
TI  - Insulin-like growth factor-I and bone mineral density.
AB  - To assess the relationship between insulin-like growth factor-I (IGF-I) and bone
      mineral density (BMD) 201 healthy postmenopausal women (age 41-68 years) within
      10 years of menopause were studied. In all subjects, BMD at the lumbar spine and
      left hip were measured using dual-energy X-ray absorptiometry and blood samples
      were obtained. In all subjects, serum IGF-I and parathyroid hormone (PTH) were
      measured. In a subgroup of these subjects serum concentrations of IGF-binding
      protein-3 (IGFBP-3), osteocalcin (OC), bone-specific alkaline phosphatase (BALP),
      tartrate-resistant acid phosphatase (TRAP), and carboxyterminal propeptide of
      type I procollagen (PICP) were also measured. Serum IGF-I correlated
      significantly with age (r = -0.159, p = 0.0241), serum OC (r = 0.226, p =
      0.0131), BALP (r = 0.259, p < 0.0001), and TRAP (r = 0.261, p < 0.0015), but not
      with PICP, PTH, or BMD at any site. Although there was a strong correlation
      between IGF-I and IGFBP-3 (r = 0.559, p < 0.0001), there was no correlation
      between IGFBP-3 and any of the markers of bone turnover (OC, BALP, TRAP, or PICP)
      nor with PTH or BMD at any site. We conclude that IGF-I and markers of bone
      turnover are related, but there is no relationship between IGF-I and BMD.

PMID- 9662126
TI  - Signal pathways that transduce growth factor-stimulated mitogenesis in bone
      cells.
AB  - This investigation examined which signal pathways are of relevance in growth
      factor-stimulated bone cell mitogenesis. Platelet-derived growth factor (PDGF)
      and insulin-like growth factor-II (IGF-II) were potent mitogens for both the MG
      63 osteoblast cell line and for primary cultures of human osteoblasts (HObs). The
      mitogenic action of both IGF-II and PDGF was attenuated by pertussis toxin (Ptx),
      by indomethacin, and by the lipoxygenase inhibitors BW755C74 and BW4AC. A
      combination of Ptx and indomethacin caused much greater inhibition but failed to
      abolish mitogenesis completely. PDGF significantly elevated inositol phosphates
      levels in both cell types; IGF-II had no effect on this pathway. In MG-63 cells,
      we demonstrated tyrosine phosphorylation of high-molecular-weight substrates
      elicited by both PDGF and IGF-II. Genistein inhibited the phosphorylation and
      mitogenic response to PDGF, but had no effect on IGF-II-induced tyrosine
      phosphorylation or mitogenesis. Another inhibitor of tyrosine kinases, methyl 2,5
      dihydroxycinnamate, (MDHC), inhibited PDGF-stimulated mitogenesis effectively in
      both cell types but only blocked IGF-II-induced mitogenesis in MG-63 cells. The
      specificity of these inhibitors suggests that particular tyrosine kinases may
      regulate growth factor-induced stimulation of bone cells.

PMID- 9662127
TI  - Mouse mammary carcinoma cell line (BALB/c-MC) stimulates osteoclast formation
      from mouse bone marrow cells through cell-to-cell contact.
AB  - We recently reported that numerous osteoclasts (OC) were formed in cocultures of
      some mouse cancer cell lines and bone marrow cells. In this study, we examined
      mechanisms by which one of the cell lines, BALB/c-MC, induces OC. BALB/c-MC dose
      dependently stimulated OC formation in cocultures. In cocultures where direct
      cell-to-cell contact between BALB/c-MC and bone marrow cells was inhibited by
      membrane filters, OC formation was not stimulated. The stimulation of OC
      formation in the coculture was completely abolished by adding 10(-7)-10(-6) mol/L
      indomethacin. The concentration of prostaglandin E2 (PGE2) in the culture media
      of cocultures with cell-to-cell contact was higher than that of cocultures
      without cell-to-cell contact or marrow cultures alone, and it reached levels
      sufficient to induce OC (11.9 +/- 5.3 ng/mL [about 3.4 x 10(-8) mol/L]). When
      BALB/c-MC or bone marrow cells were fixed with formalin and then cocultured with
      bone marrow cells or BALB/c-MC, respectively, the concentration of PGE2 in the
      culture media of cocultures of fixed BALB/c-MC and bone marrow cells increased,
      whereas that of cocultures of BALB/c-MC and fixed bone marrow cells did not
      increase. These results indicate that BALB/c-MC stimulate OC formation through
      direct cell-to-cell contact with bone marrow cells, and PGE2 released from bone
      marrow cells through direct cell-to-cell contact are involved in OC formation by
      the cell line.

PMID- 9662128
TI  - Caspases (interleukin-1beta-converting enzyme family proteases) are involved in
      the regulation of the survival of osteoclasts.
AB  - Osteoclast-like multinucleated cells (OCLs) were prepared on collagen gels in a
      coculture system of mouse bone marrow cells and osteoblasts, and purified by
      collagenase and a subsequent pronase treatment. More than 80% of the purified
      OCLs were found to undergo apoptotic cell death by 48 h during the culture in a
      culture medium containing 10% fetal bovine serum (FBS). Withdrawal of FBS from
      the culture medium accelerated the cell death, which induced more than 80% of
      OCLs to undergo apoptotic cell death by as early as 18 h. Two peptide inhibitors
      of caspases (interleukin-1beta-converting enzyme family proteases),
      benzyloxycarbonyl-Val-Ala-Asp (OMe)-fluoromethyl ketone (Z-VAD-FMK) and
      benzyloxycarbonyl-Asp-Glu-Val-Asp (OMe)-fluoromethyl ketone (Z-DEVD-FMK),
      extended the survival time of OCLs in the presence and absence of 10% FBS, but
      the effect was rather limited in the absence of FBS. Because interleukin-1alpha
      (IL-1alpha) and the macrophage colony stimulating factor (M-CSF) are known to
      promote the survival of osteoclasts, we examined the effect of the peptide
      inhibitors and these cytokines. Combinations of the peptide inhibitors and IL
      1alpha, or the peptide inhibitors and M-CSF, were more effective than the
      inhibitors alone. When endogenous caspase activities of OCLs were analyzed using
      fluorescence peptide substrates, the activities, in particular, caspase-3 (CPP32)
      like activity, were markedly increased in OCLs by the withdrawal of FBS from the
      culture medium. IL-1alpha and M-CSF suppressed the activation of the caspases. In
      addition, western blot analysis revealed that the expression of Bcl-2, which
      inhibits the activation of caspases, was very weak or even negligible in OCLs.
      Taken together, these results suggest that the caspases are involved in the
      regulation of survival and apoptotic cell death of osteoclasts.

PMID- 9662129
TI  - Withdrawal of parathyroid hormone treatment causes rapid resorption of newly
      formed vertebral cancellous and endocortical bone in old rats.
AB  - When administered intermittently, parathyroid hormone (PTH) is a strong anabolic
      agent, increasing both bone mass and bone mechanical strength and competence.
      This study evaluates the fate of PTH-induced bone in vertebral bodies after
      withdrawal of PTH treatment in normal old rats. Sixty-seven 21-month-old male
      rats were treated with 62 microg/kg/day PTH(1-34) for 8 weeks, followed by saline
      or bisphosphonate (risedronate, 5 microg/kg twice a week) for another 8 weeks.
      The rats were scanned by dual-energy X-ray absorptiometry at intervals. The bone
      mineral content (BMC) of L2-5 increased by 33% during the PTH treatment. The BMC
      started decreasing shortly after withdrawal of PTH and continued to decline
      during the 8 weeks after withdrawal of PTH. Risedronate, however, prevented this
      decrease in BMC. All rats were labeled with tetracycline and calcein 3 weeks and
      1 week before the cessation of PTH therapy. In the cancellous bone, PTH increased
      the mineralized surface: 32.9% +/- 2.8% (mean +/- standard error of the mean) vs.
      controls 12.0% +/- 1.5%, the mineral appositional rate (0.65 +/- 0.02 to 0.88 +/-
      0.06 microm/day), and the cancellous bone volume (BV/TV: 14.5% +/- 0.7% to 27.5%
      +/- 1.7%). Withdrawal of PTH induced a fast and pronounced bone resorption,
      decreasing both the extent of the fluorochrome labels and the cancellous bone
      volume to control values. Risedronate prevented this resorption. In the cortical
      bone of the vertebral shell, PTH induced large increases in the endocortical
      mineralized surface, mineral appositional rate, and cortical area. The
      endocortical fluorochrome labels were, however, resorbed after withdrawal of PTH.
      Risedronate maintained both the fluorochrome labels and the cortical area. At the
      periosteum, the response to PTH was less evident, however, and hardly any
      labeling was seen at the periosteum facing the vertebral canal either in the
      controls or in the PTH-treated rats. The compressive strength of the vertebral
      body specimens increased with PTH treatment whether measured in newtons (317 +/-
      23 to 623 +/- 54 N), normalized to cross-sectional area (23.0 +/- 1.4 to 44.7 +/-
      2.5 N/mm2), or to ash content per millimeter height (58 +/- 2 to 76 +/- 2 N x
      mm/mg). Withdrawal of PTH decreased the compressive strength and competence to
      control values. Risedronate, however, maintained the PTH-induced mechanical
      strength and competence. The study discloses that even in very old rats
      withdrawal of PTH treatment causes a rapid and pronounced decline in the bone
      mass deposited during PTH treatment; treatment with risedronate can, however,
      maintain the PTH-induced bone properties in the axial skeleton of old rats.

PMID- 9662130
TI  - Fractal properties of cancellous bone of the iliac crest in vertebral crush
      fracture.
AB  - Fractal analysis is a method for describing complex shapes, including the
      cancellous structure of bone. It describes the surface texture and form of
      individual trabecular profiles and the overall cancellous structure. Sixty-four
      postmenopausal women with symptoms of back pain were referred for investigation
      for osteoporosis. The patients were divided into two groups for comparison:
      vertebral crush fracture (n = 31, mean age 68.58 +/- 6.47 years), and no
      vertebral crush fracture (n = 33, mean age 63.36 +/- 7.21 years). Cores of
      cancellous bone, 3 mm in diameter, were taken from the iliac crest and sectioned.
      A box-counting method implemented on an image analyzer was used to measure the
      fractal dimension. Three fractal dimensions describing trabecular surface texture
      (fractal 1), trabecular shape (fractal 2), and trabecular arrangement (fractal 3)
      were measured, indicating that cancellous bone has sectional self-similarity.
      Conventional histomorphometry was also performed on the samples. The results show
      that fractal 2 is significantly lower in the vertebral crush fracture group than
      in the nonfracture group (1.15 +/- 0.10 < 1.23 +/- 0.090, p < 0.0013). The
      histomorphometric analysis shows that bone surface total volume (p < 0.0002),
      trabecular number (p < 0.0001), and osteoid surface bone surface (p < 0.028) are
      significantly lower in the fracture group than the nonfracture group. Eroded
      surface/bone surface (p < 0.056) follows this trend, whereas trabecular
      separation (p < 0.001) is significantly higher in the fracture group than in the
      nonfracture group. Fractal 1 and fractal 3 were not significantly different
      between study groups. The fractal dimension detects changes in the cancellous
      architecture and gives information about iliac bone transformation in
      postmenopausal women with vertebral fracture.

PMID- 9662131
TI  - Morphometric analysis of human bone biopsies: a quantitative structural
      comparison of histological sections and micro-computed tomography.
AB  - As a part of the European Union BIOMED I study "Assessment of Bone Quality in
      Osteoporosis," the trabecular structure of transiliac bone biopsies was assessed
      by conventional histomorphometry and by three-dimensional microcomputed
      tomography (microCT). Sixty-three cylindrical human transiliac bone specimens
      were obtained post mortem from 27 women and 36 men (age 23-92 years) and
      evaluated morphometrically in this study. For the conventional histomorphometric
      analysis, a pair of four undecalcified sections were prepared from two regions in
      the mediolateral plane of the bone cores. The sections were stained with the von
      Kossa technique to obtain high-contrast two-dimensional images. Prior to the
      histologic sectioning the samples were measured with a desktop microCT, providing
      a 14 microm nominal resolution. The morphometric parameters computed by both
      methods in two or three dimensions, respectively, were bone volume density
      (BV/TV), bone surface density (BS/TV), trabecular thickness (Tb.Th), and
      trabecular separation (Tb.Sp). Results showed highly significant (p < 0.0001)
      correlations between conventional histology and microCT for BV/TV (r = 0.93),
      BS/TV (r = 0.91), Tb.Th (r = 0.84), and Tb.Sp (r = 0.91). The mean percentage
      differences between histology and microCT ranged from 2.5% (BV/TV) to 6.1%
      (Tb.Th). The high correlations and the low differences in terms of absolute
      numbers between conventional histomorphometric and microtomographic analysis are
      very promising for the use of micro-tomographic imaging. MicroCT is a
      nondestructive, fast, and very precise procedure that allows the measurement of
      cancellous and compact bone in unprocessed biopsies or small bones, as well as a
      fully automatic determination of three-dimensional morphometric indices.

PMID- 9662132
TI  - Changes in the fracture toughness of bone may not be reflected in its mineral
      density, porosity, and tensile properties.
AB  - Age-related changes in the skeleton often lead to an increase in the
      susceptibility of bone to fracture. Such changes most likely occur in the
      constituents of bone, namely, the mineral and organic phases, and in their
      spatial arrangement manifested as orientation and microstructure. In the past,
      however, bone loss or decline in bone mineral density has been considered to be
      the major contributing factor for the increased risk of bone fractures, and
      elastic modulus and ultimate strength have been commonly used to assess bone
      quality and strength. However, whether these properties provide sufficient
      information regarding the likelihood of bone to fracture remains debatable. Using
      a novel fracture toughness test, which measures the energy or stress intensity
      required to propagate a crack within a material, the objective of this study was
      to investigate if the mineral density and mechanical properties of bone can
      accurately predict bone fragility as measured by fracture toughness. Changes in
      fracture toughness (K(IC)), bone mineral density (BMD), elastic modulus (E),
      yield and ultimate strength (sigma y and sigma s), porosity (P0), and
      microhardness (Hv) of bone were examined as a function of age in a baboon model.
      With increasing age, the fracture toughness of bone decreased, and its
      microhardness increased. However, no significant changes were found in BMD, E,
      P0, sigma y, and sigma s as a function of age. In addition, simple regression
      analyses revealed no significant correlation between bone fracture toughness and
      the other parameters, except for microhardness of bone. The results of this study
      indicate that changes in bone fracture toughness may not be necessarily reflected
      in its mineral density, porosity, elastic modulus, yield strength, and ultimate
      strength.

PMID- 9662133
TI  - Amnesia, the hippocampus, and episodic memory.

PMID- 9662134
TI  - Episodic and declarative memory: role of the hippocampus.
AB  - The fact that medial temporal lobe structures, including the hippocampus, are
      critical for declarative memory is firmly established by now. The understanding
      of the role that these structures play in declarative memory, however, despite
      great efforts spent in the quest, has eluded investigators so far. Given the
      existing scenario, novel ideas that hold the promise of clarifying matters should
      be eagerly sought. One such idea was recently proposed by Vargha-Khadem and her
      colleagues (Science 1997; 277:376-380) on the basis of their study of three young
      people suffering from anterograde amnesia caused by early-onset hippocampal
      pathology. The idea is that the hippocampus is necessary for remembering ongoing
      life's experiences (episodic memory), but not necessary for the acquisition of
      factual knowledge (semantic memory). We discuss the reasons why this novel
      proposal makes good sense and why it and its ramifications should be vigorously
      pursued. We review and compare declarative and episodic theories of amnesia, and
      argue that the findings reported by Vargha-Khadem and her colleagues fit well
      into an episodic theory that retains components already publicized, and adds new
      ones suggested by the Vargha-Khadem et al. study. Existing components of this
      theory include the idea that acquisition of factual knowledge can occur
      independently of episodic memory, and the idea that in anterograde amnesia it is
      quite possible for episodic memory to be more severely impaired than semantic
      memory. We suggest a realignment of organization of memory such that declarative
      memory is defined in terms of features and properties that are common to both
      episodic and semantic memory. The organization of memory thus modified gives
      greater precision to the Vargha-Khadem et al. neuroanatomical model in which
      declarative memory depends on perihippocampal cortical regions but not on the
      hippocampus, whereas episodic memory, which is separate from declarative memory,
      depends on the hippocampus.

PMID- 9662135
TI  - Episodic memory, semantic memory, and amnesia.
AB  - Episodic memory and semantic memory are two types of declarative memory. There
      have been two principal views about how this distinction might be reflected in
      the organization of memory functions in the brain. One view, that episodic memory
      and semantic memory are both dependent on the integrity of medial temporal lobe
      and midline diencephalic structures, predicts that amnesic patients with medial
      temporal lobe/diencephalic damage should be proportionately impaired in both
      episodic and semantic memory. An alternative view is that the capacity for
      semantic memory is spared, or partially spared, in amnesia relative to episodic
      memory ability. This article reviews two kinds of relevant data: 1) case studies
      where amnesia has occurred early in childhood, before much of an individual's
      semantic knowledge has been acquired, and 2) experimental studies with amnesic
      patients of fact and event learning, remembering and knowing, and remote memory.
      The data provide no compelling support for the view that episodic and semantic
      memory are affected differently in medial temporal lobe/diencephalic amnesia.
      However, episodic and semantic memory may be dissociable in those amnesic
      patients who additionally have severe frontal lobe damage.

PMID- 9662136
TI  - Amnesia and the organization of the hippocampal system.
AB  - Early hippocampal injury in humans has been found to result in a limited form of
      global anterograde amnesia. At issue is whether the limitation is qualitative,
      with the amnesia reflecting substantially greater impairment in episodic than in
      semantic memory, or only quantitative, with both episodic and semantic memory
      being partially and equivalently impaired. Evidence from neuroanatomical and
      lesion studies in animals suggests that the hippocampus and subhippocampal
      cortices form a hierarchically organized system, such that the greatest
      convergence of information (and, by implication, the richest amount of
      association) takes place within the hippocampus, located at the top of the
      hierarchy. On the one hand, this evidence is consistent with the view that
      selective hippocampal damage produces a differential impairment in context-rich
      episodic memory as compared with context-free semantic memory, because only the
      latter can be supported by the subhippocampal cortices. On the other hand, given
      the system's hierarchical form of organization, this dissociation of deficits is
      difficult to prove, because a quantitatively limited deficit will nearly always
      be a viable alternative. A final choice between the alternative views is
      therefore likely to depend less on further evidence gathered in brain-injured
      patients than on which view accounts for more of the data gathered from
      converging approaches to the problem.

PMID- 9662137
TI  - Functional interconnections between CA3 and the dentate gyrus revealed by current
      source density analysis.
AB  - The physiological interactions between the dentate gyrus (DG) and CA3 were
      studied in urethane-anesthetized rats by using field potential recording and
      current source density (CSD) analysis. Stimulation of CA3b resulted in a short
      latency (<2.5-ms onset latency) antidromic population spike in both the DG and
      CA3c. An excitation (current sink) at the middle molecular layer (MML) was
      observed at 3-ms latency, possibly mediated by the backfiring of perforant path
      fibers that projected to both DG and CA3. CA3 stimulation also resulted in a sink
      at the dendritic layers of CA3c, which was likely mediated by excitatory CA3
      recurrent collaterals. It was inferred that the DG was excited at the inner
      molecular layer (IML) after stimulation near the CA3b/CA3c border. This IML
      excitation (sink) probably resulted from orthodromic CA3 or hilar projections to
      the IML and not from mossy fiber backfiring. The IML and the CA3c dendritic sinks
      were blocked by an intracerebroventricular injection of a non-N-methyl-D
      aspartate receptor antagonist, 6-cyano-7-nitroquinoxaline-2, 3-dione, but not by
      a gamma-aminobutyric acid type A (GABA(A)) receptor antagonist, bicuculline. CA3b
      stimulation evoked population spike bursts (3-7-ms latency) in both DG and CA3c
      when GABA(A) inhibition was suppressed by bicuculline, thus confirming that the
      excitatory afferents project from CA3b to DG and CA3c. A CA3 conditioning
      stimulus pulse given 30-200 ms before a perforant-path test pulse increased the
      amplitude of the perforant-path-evoked DG population spike (as compared with the
      test response without conditioning). After a moderate-intensity stimulation of
      CA3, a late (<20-ms latency) excitation of the MML of the DG was found. The late
      DG excitation was blocked by procaine injection at the medial perforant path,
      suggesting its origin from the medial entorhinal cortex. In conclusion, rich
      interactions between CA3 and other hippocampal structures were studied
      quantitatively by CSD analysis in vivo. We infer that CA3 provides an early
      excitatory feedback path to DG through recurrent collaterals or hilar
      interneurons and a late feedback through the medial entorhinal cortex.

PMID- 9662139
TI  - Theta oscillations in somata and dendrites of hippocampal pyramidal cells in
      vivo: activity-dependent phase-precession of action potentials.
AB  - Theta frequency field oscillation reflects synchronized synaptic potentials that
      entrain the discharge of neuronal populations within the approximately 100-200 ms
      range. The cellular-synaptic generation of theta activity in the hippocampus was
      investigated by intracellular recordings from the somata and dendrites of CA1
      pyramidal cells in urethane-anesthetized rats. The recorded neurons were verified
      by intracellular injection of biocytin. Transition from non-theta to theta state
      was characterized by a large decrease in the input resistance of the neuron (39%
      in the soma), tonic somatic hyperpolarization and dendritic depolarization. The
      probability of pyramidal cell discharge, as measured in single cells and from a
      population of extracellularly recorded units, was highest at or slightly after
      the negative peak of the field theta recorded from the pyramidal layer. In
      contrast, cyclic depolarizations in dendrites corresponded to the positive phase
      of the pyramidal layer field theta (i.e. the hyperpolarizing phase of somatic
      theta). Current-induced depolarization of the dendrite triggered large amplitude
      slow spikes (putative Ca2+ spikes) which were phase-locked to the positive phase
      of field theta. In the absence of background theta, strong dendritic
      depolarization by current injection led to large amplitude, self-sustained
      oscillation in the theta frequency range. Depolarization of the neuron resulted
      in a voltage-dependent phase precession of the action potentials. The voltage
      dependent phase-precession was replicated by a two-compartment conductance model.
      Using an active (bursting) dendritic compartment spike phase advancement of
      action potentials, relative to the somatic theta rhythm, occurred up to 360
      degrees. These data indicate that distal dendritic depolarization of the
      pyramidal cell by the entorhinal input during theta overlaps in time with somatic
      hyperpolarization. As a result, most pyramidal cells are either silent or
      discharge with single spikes on the negative portion of local field theta (i.e.,
      when the somatic region is least polarized). However, strong dendritic excitation
      may overcome perisomatic inhibition and the large depolarizing theta rhythm in
      the dendrites may induce spike bursts at an earlier phase of the extracellular
      theta cycle. The magnitude of dendritic depolarization is reflected by the timing
      of action potentials within the theta cycle. We hypothesize that the competition
      between the out-of-phase theta oscillation in the soma and dendrite is
      responsible for the advancement of spike discharges observed in the behaving
      animal.

PMID- 9662138
TI  - Corticotropin-releasing hormone (CRH)-containing neurons in the immature rat
      hippocampal formation: light and electron microscopic features and colocalization
      with glutamate decarboxylase and parvalbumin.
AB  - Corticotropin-releasing hormone (CRH) excites hippocampal neurons and induces
      death of selected CA3 pyramidal cells in immature rats. These actions of CRH
      require activation of specific receptors that are abundant in CA3 during early
      postnatal development. Given the dramatic effects of CRH on hippocampal neurons
      and the absence of CRH-containing afferents to this region, we hypothesized that
      a significant population of CRHergic neurons exists in developing rat
      hippocampus. This study defined and characterized hippocampal CRH-containing
      cells by using immunocytochemistry, ultrastructural examination, and
      colocalization with gamma-aminobutyric acid (GABA)-synthesizing enzyme and
      calcium-binding proteins. Numerous, large CRH-immunoreactive (ir) neurons were
      demonstrated in CA3 strata pyramidale and oriens, fewer were observed in the
      corresponding layers of CA1, and smaller CRH-ir cells were found in stratum
      lacunosum-moleculare of Ammon's horn. In the dentate gyrus, CRH-ir somata resided
      in the granule cell layer and hilus. Ultrastructurally, CRH-ir neurons had aspiny
      dendrites and were postsynaptic to both asymmetric and symmetric synapses. CRH-ir
      axon terminals formed axosomatic and axodendritic symmetric synapses with
      pyramidal and granule cells. Other CRH-ir terminals synapsed on axon initial
      segments of principal neurons. Most CRH-ir neurons were coimmunolabeled for
      glutamate decarboxylase (GAD)-65 and GAD-67 and the majority also contained
      parvalbumin, but none were labeled for calbindin. These results confirm the
      identity of hippocampal CRH-ir cells as GABAergic interneurons. Further, a
      subpopulation of neurons immunoreactive for both CRH and parvalbumin and located
      within and adjacent to the principal cell layers consists of basket and
      chandelier cells. Thus, axon terminals of CRH-ir interneurons are strategically
      positioned to influence the excitability of the principal hippocampal neurons via
      release of both CRH and GABA.

PMID- 9662140
TI  - Serotonin neuronal release from dorsal hippocampus following electrical
      stimulation of the dorsal and median raphe nuclei in conscious rats.
AB  - We have studied 5-hydroxytryptamine (5-HT) release in the hippocampal formation
      following electrical stimulation of the dorsal and median raphe nuclei in the
      behaving rat. The primary finding in this study is a decrease in neuronal release
      of serotonin in the dorsal hippocampal formation following electrical stimulation
      of either the dorsal or median raphe nucleus in conscious rats. At no time did
      electrical stimulation of either raphe nucleus result in behavioral, including
      vigilance state, changes. The amount of 5-HT released was found to be frequency
      dependent with higher frequencies (20 Hz) producing larger decreases in release
      of 5-HT. However, the pattern of release differs between the two raphe nuclei.
      Extracellular levels of 5-HT decrease during stimulation of the dorsal raphe,
      whereas levels decrease only following cessation of stimulation of the median
      raphe nucleus. This may relate to the patterns of innervation of the dorsal
      hippocampal formation by these two midbrain raphe nuclei and also may reflect an
      inhibition of median raphe cell firing during stimulation of the dorsal raphe.
      Electrical stimulation of the dorsal raphe in anesthetized animals resulted in an
      enhanced release of 5-HT. The suppression of 5-HT release in the dorsal
      hippocampal formation in behaving animals was long-lasting (over 2 h), suggesting
      that the control mechanisms that regulate 5-HT release operate over a long time
      course. This difference in release between non-anesthetized and anesthetized
      animals may relate to anesthesia blocking long- and/or short-loop serotonin
      recurrent axonal collaterals negatively feeding back onto 5-HT1A and 5-HT1D
      somatodendritic autoreceptors on raphe neurons. Further, the anesthetized animal
      has diminished monoaminergic "gating" influences on the hippocampal formation,
      whereas the behaving animal is more complex with behavioral (vigilance) states
      associated with different patterns of gating of information flow through the
      hippocampal formation.

PMID- 9662141
TI  - Glutamate-stimulated neuropeptide Y mRNA expression in the rat dentate gyrus: a
      prominent role of metabotropic glutamate receptors.
AB  - The influence of intrahippocampal injections of glutamate receptor agonists on
      neuropeptide Y (NPY) mRNA expression was investigated in granule cells and
      interneurons of the rat dentate gyrus. One day after local injection of non
      neurodegenerative doses (20 and 70 nmol) of the metabotropic glutamate receptor
      agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate [(1S,3R)ACPD], NPY mRNA
      levels were more than doubled in ipsilateral granule cells and interneurons.
      Doses of 200 and 400 nmol caused up to 15.9- and 4.6-fold mRNA increases in
      granule cells and interneurons, respectively. The group I metabotropic glutamate
      receptor agonist (RS)-3,5-dihydroxyphenylglycine (DHPG; 50 nmol), but not the
      group III receptor agonist L(+)-2-amino-4-phosphonobutyrate (L-AP4; 20 and 200
      nmol) exerted a similar action. The general metabotropic glutamate receptor
      antagonist (+)-alpha-methyl-4-carboxyphenylglycine (MCPG; 200 nmol), the group I
      receptor antagonist (S)-4-carboxyphenylglycine (4-CPG; 200 nmol) and the N-methyl
      D-aspartate (NMDA) receptor antagonist MK-801 (1 mg/kg; i.p.) partially blocked
      the (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate-induced increase in NPY mRNA in
      granule cells, but not in interneurons. (S)-4-carboxyphenylglycine (200 nmol) by
      itself increased NPY mRNA levels in ipsilateral interneurons threefold,
      indicating the activation of phospholipase D coupled receptors. Non
      neurodegenerative doses of (RS)-alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionate (AMPA, 0.3 nmol) caused modest increases in NPY mRNA levels
      in ipsilateral interneurons, whereas neurodegenerative doses (1-10 nmol) induced
      markedly increased NPY mRNA levels in granule cells (up to 11-fold) and
      interneurons (up to threefold). It is suggested that activation of metabotropic
      glutamate receptors stimulates NPY mRNA expression in granule cells and
      interneurons in the rat dentate gyrus. Whereas in granule cells NPY mRNA
      upregulation is preferentially mediated by group I metabotropic glutamate
      receptors, it may involve ionotropic and metabotropic glutamate receptors in
      interneurons.

PMID- 9662142
TI  - Effects of GABA(A) inhibition on the expression of long-term potentiation in CA1
      pyramidal cells are dependent on tetanization parameters.
AB  - Long-term potentiation (LTP) of excitatory synaptic responses of principal
      neurons in the hippocampus is accompanied by changes in GABAergic inhibition
      mediated by interneurons. The impact of inhibition on LTP of excitatory
      postsynaptic responses in CA1 pyramidal cells was assessed by monitoring changes
      in field potentials evoked by Schaffer collateral stimulation in hippocampal
      slices in vitro. First, to determine the effect of inhibition on population
      EPSPs, slices were exposed to the GABA(A) receptor antagonist bicuculline (10
      microM). Both the slope and amplitude of field EPSPs (fEPSPs) were significantly
      enhanced by bicuculline indicating that inhibition modulates excitatory
      postsynaptic responses of pyramidal cells. To assess if stimulation-dependent
      changes in inhibition influence LTP of excitatory responses of pyramidal cells,
      LTP was examined in the presence and absence of bicuculline (20 microM) following
      either 100 Hz tetanization, or theta-patterned stimulation (short bursts
      delivered at 5 Hz). In normal medium, 100 Hz stimulation produced marked short
      term potentiation that decayed 5-10 min post-tetanus and both stimulation
      paradigms produced similar LTP at 30 min post-tetanus. In comparison, LTP of the
      fEPSP slope and amplitude was significantly enhanced after theta-patterned
      stimulation, but not after 100 Hz stimulation, in bicuculline. The greater
      potentiation of field responses following theta-patterned stimulation in the
      presence of bicuculline indicates that a larger potentiation of excitatory
      responses was unmasked during suppression of inhibitory inputs. These results
      suggest that a long-lasting enhancement of inhibition in pyramidal cells was also
      induced following theta-patterned stimulation in normal ACSF. Since suppression
      of inhibition did not uncover a significantly larger potentiation following 100
      Hz tetanization, the influence of inhibition on LTP of excitatory responses
      appears to be stimulation-dependent. In conclusion, theta-patterned stimulation
      appears to be more effective at inducing plasticity within inhibitory circuits,
      and this plasticity may partially offset concurrent increases in the excitability
      of the CA1 network.

PMID- 9662143
TI  - Bidirectional modulation of AMPA receptor properties by exogenous phospholipase
      A2 in the hippocampus.
AB  - The synaptic modifications underlying long-term potentiation (LTP) and long-term
      depression (LTD) of synaptic transmission in various brain structures may result
      from changes in the properties of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionate (AMPA) subtype of glutamate receptors. In the present study, we report
      that treatment of rat synaptoneurosomes with increasing concentrations of
      phospholipase A2 (PLA2) produces a biphasic effect on AMPA receptor binding, with
      low concentrations causing a decrease and high concentrations an increase in
      agonist binding. Analysis of the saturation kinetics of 3H-AMPA binding revealed
      that the biphasic effect of PLA2 was due to modifications in receptor affinity
      and not to changes in the maximum number of binding sites for AMPA receptors. The
      12-lipoxygenase inhibitors preferentially reduced PLA2-induced decrease in AMPA
      binding and treatment of hippocampal synaptoneurosomes with arachidonic acid (AA)
      or 12-HPETE, the first metabolite generated from the hydrolysis of AA by 12
      lipoxygenases, decreased 3H-AMPA binding. Moreover, electrophysiological
      experiments indicated that the 12-lipoxygenase inhibitor baicalein totally
      blocked LTD formation in area CA1 of hippocampal slices. The decrease in 3H-AMPA
      binding elicited by low concentrations of PLA2, as well as the level of LTD, were
      partially reduced by AA-861, a 5-lipoxygenase inhibitor, while the cyclooxygenase
      inhibitor indomethacin did not prevent LTD formation or the effects of PLA2 on 3H
      AMPA binding. Our results provide evidence for a possible involvement of
      lipoxygenase metabolites in the regulation of AMPA receptor during synaptic
      depression. In addition, they strongly support the idea that the same biochemical
      pathway, i.e., NMDA receptor activation and endogenous PLA2 stimulation, may
      represent a common mechanism resulting in AMPA receptor alterations for both LTP
      and LTD formation.

PMID- 9662144
TI  - Temporospatial heterogeneity of myocardial perfusion and blood volume in the
      porcine heart wall.
AB  - Spatial heterogeneity of myocardial perfusion has been recognized for many years.
      Whether this is primarily the result of heterogeneity of parameters such as
      myocardial metabolism, of intramyocardial mechanical forces, or of vasomotor
      function within the myocardial microcirculation, is not clear. A practical
      problem is that it has been almost impossible to measure any two of these
      parameters simultaneously in the same piece of myocardium so that an unambiguous
      correlation, much less a cause-and-effect relationship, has been difficult to
      establish. In this study of six anesthetized pigs, we propose that whole-body
      computed tomography is a method for providing the simultaneous measurement of
      heterogeneity of myocardial perfusion (F) and myocardial blood volume (rho). The
      first finding was that the empirical relationship rho=AF+BF(0.5) between
      myocardial blood flow (F) and intramyocardial blood volume (rho) is maintained
      over a range of sizes of regions of interest (approximately 1 to 0.125 cm3)
      within the myocardium of each individual animal despite the spatial heterogeneity
      of the F and the rho values. The value of A ranges from 0.014 to 0.021 min and of
      B ranges from 0.061 to 0.076 ml(0.5) g(-0.5) min(0.5). A second finding was that
      the pattern of spatial heterogeneity of F and of rho remained reasonably stable
      over at least a 1 h period.

PMID- 9662145
TI  - Flow-driven diameter response in rat femoral arteries perfused in vitro.
AB  - The effects of flow and flow changes on arterial diameter were investigated in
      vitro on isolated rat femoral arteries. Segments of femoral arteries were
      excised, mounted on microcannulas, and perfused with Tyrode's solution (37
      degrees C). Perfusion pressure was kept constant at 90 mm Hg. The mean external
      diameter after equilibration at a transmural pressure of 90 mm Hg was 720 +/- 50
      microm (n = 12). Vessels were then constricted with norepinephrine (1 microM in
      the superfusion solution) to 77% +/- 13% of the resting diameter; acetylcholine
      was used to check endothelial function. The external diameter was measured
      continuously using video microscopy. The arteries were subjected to two different
      types of flow variations: (a) step changes in flow (increase and decrease, n = 6)
      and (b) low-frequency sinusoidal flow variations (frequencies ranging from 0.002
      to 0.1 Hz, n = 11). Flow ranged from 0 to 800 microl/min (shear stress ranging
      from 0 to 15 dyn/cm2). All measured vessels constricted as flow increased. Flow
      steps induced exponential-like contractions (flow increase) or relaxations (flow
      decrease) with mean characteristic time constants 31 +/- 4 and 22 +/- 2 s,
      respectively. Sinusoidal flow oscillations induced sinusoidal diameter
      oscillations with a time delay. An increase in the frequency of the flow led to a
      decrease of both the amplitude of the flow-induced diameter oscillations and the
      phase shift between flow and diameter. The dynamic diameter response to flow
      changes could be characterized by a first-order low-pass filter with a time
      constant of 22 s.

PMID- 9662146
TI  - Stress variations in the human aortic root and valve: the role of anatomic
      asymmetry.
AB  - The asymmetry of the aortic valve and aortic root may influence their
      biomechanics, yet was not considered in previous valve models. This study
      developed an anatomically representative model to evaluate the regional stresses
      of the valve within the root environment. A finite-element model was created from
      magnetic-resonance images of nine human valve-root specimens, carefully
      preserving their asymmetry. Regional thicknesses and anisotropic material
      properties were assigned to higher-order elastic shell elements representing the
      valve and root. After diastolic pressurization, peak principal stresses were
      evaluated for the right, left, and noncoronary leaflets and root walls. Valve
      stresses were highest in the noncoronary leaflet (538 kPa vs right 473 kPa vs
      left 410 kPa); peak stresses were located at the free margin and belly near the
      coaptation surfaces (averages 537 and 482 kPa for all leaflets, respectively).
      Right and noncoronary sinus stresses were 21% and 10% greater than the left
      sinus. In all sinuses, stresses near the annulus were higher than near the
      sinotubular junction. Stresses vary across the valve and root, likely due to
      their inherent morphologic asymmetry and stress sharing. These factors may
      influence bioprosthetic valve durability and the incidence of isolated sinus
      dilatation.

PMID- 9662147
TI  - Negative pressure transients with mechanical heart-valve closure: correlation
      between in vitro and in vivo results.
AB  - Negative pressure transients (NPT) recorded in a single closing event of
      mechanical valves in the mitral position in an in vitro setup are compared with
      data recorded in the left atrium in vivo with the valves implanted in the mitral
      position in an animal model. The loading at valve closure (dP/dtCL) computed from
      the in vivo ventricular pressure recording (ranging from 700 to 2300 mm Hg/s)
      agreed with the magnitudes predicted in our earlier in vitro experiments (750
      3000 mm Hg/s). The NPT signals and the corresponding power spectral density plots
      from the in vivo data were in qualitative agreement with those recorded in vitro.
      The NPT magnitudes were found to be below the vapor pressure for blood in
      mechanical valves with rigid occluders suggesting a potential for the valve to
      cavitate in vivo. Our in vivo results also suggest that the valves with flexible
      occluders are less likely to cavitate. The correlation of the in vitro and in
      vivo data also suggests that the flexibility of valve housing used in the in
      vitro studies is not an important factor in the dynamics of mechanical valve
      closure in vivo.

PMID- 9662148
TI  - Normal three-dimensional pulmonary artery flow determined by phase contrast
      magnetic resonance imaging.
AB  - In this study, an application was developed to measure three-dimensional blood
      flow in the main, right, and left pulmonary arteries of seven healthy volunteers
      using phase contrast magnetic resonance imaging (MRI). Presently, no other
      noninvasive technique is capable of providing this information. Flow, mean
      velocity, kinetic energy, and cross-sectional area were measured at multiple
      phases of the cardiac cycle and were consistent with previously reported values
      measured with one-dimensional velocity encoded MRI and Doppler echocardiography.
      Additionally, axial, circumferential, and radial shear stresses near the wall of
      the vessel at multiple phases of the cardiac cycle were estimated using the in
      plane velocities. All three shear stresses were relatively constant along the
      vessel wall and throughout the cardiac cycle (approximately 7 dyn/cm2). This
      three-dimensional characterization of normal pulmonary blood flow provides a base
      line to which effects of altered pulmonary artery flow patterns in disease can be
      compared. [Morgan, V. L., T. P. Graham, Jr., and C. H. Lorenz. Circulation Suppl.
      94:I-417 (abstract), 1996].

PMID- 9662149
TI  - A model study of intramural dispersion of action potential duration in the canine
      pulmonary conus.
AB  - Regional gradients of action potential duration (APD) due to electrophysiological
      differences between endocardial, midmyocardial, and epicardial myocytes may exist
      across the ventricular wall. In addition, activation sequence-induced gradients
      of APD may occur if intramural fiber rotation accelerates or decelerates the
      depolarization wave front. To investigate relative contributions of regional and
      activation sequence-induced gradients to intramural APD dispersion, we simulated
      action potential propagation in two-dimensional models with idealized geometries
      representing the canine pulmonary conus. Ionic currents for endocardial myocytes
      were described using the Luo-Rudy membrane equations. Modifications to I(Ks)
      approximated action potentials of epicardial and midmyocardial cells. Spatial
      coupling was modeled with a bidomain representation of tissue structure that
      included unequal anisotropic conductivity ratios. Activation sequence-induced
      gradients reached 69 ms cm(-1) during a nonuniform activation sequence where the
      change in orientation between endocardial and epicardial fibers accelerated the
      depolarization wave front. Regional gradients reached 133 ms cm(-1) at the
      boundary between endocardial and midmyocardial cells. When regional and
      activation sequence-induced gradients were oriented in opposite directions,
      overall APD dispersion decreased. When the gradients were oriented in the same
      direction, overall dispersion measured as high as 202 ms cm(-1). This gradient
      exceeded values previously estimated as sufficient to induce cardiac arrhythmia
      during premature stimulation and suggests that regional and activation sequence
      induced gradients increase arrhythmia vulnerability in the presence of other
      arrhythmogenic conditions.

PMID- 9662150
TI  - Electrical impedance cardiography using artificial neural networks.
AB  - This study evaluates the use of artificial neural networks to estimate stroke
      volume from pre-processed, thoracic impedance plethysmograph signals from 20
      healthy subjects. Standard back-propagation was used to train the networks, with
      Doppler stroke volume estimates as the desired output. The trained networks were
      then compared to two classical biophysical approaches. The coefficient of
      determination (R2 x 100%) between the biophysical approaches and the Doppler was
      8.20% and 9.90%, while it was 77.38% between the best neural network and the
      Doppler. Among these methods, only the neural network residuals had a significant
      zero mean Gaussian distribution (alpha=0.05). Our results indicate that an
      invertible relationship may exist between thoracic bioimpedance and stroke
      volume, and that artificial neural networks may offer a potentially advantageous
      approach for estimating stroke volume from thoracic electrical impedance, both
      because of their ease of use and their lack of confounding assumptions.

PMID- 9662151
TI  - Electroporation and shock-induced transmembrane potential in a cardiac fiber
      during defibrillation strength shocks.
AB  - Experimental studies have shown that the magnitude of the shock-induced
      transmembrane potential (Vm) saturates with increasing electric field strength.
      This study uses a mathematical model to investigate the effects of
      electroporation and membrane kinetics on Vm in a cardiac fiber. The model
      consists of the core conductor equation for a one-dimensional fiber, where
      excitability is represented by the Luo-Rudy dynamic model (1994-1995) and
      electroporation is described by a membrane conductance that increases
      exponentially with Vm squared. For shocks delivered during the plateau of an
      action potential, the model reproduces the experimentally observed saturation of
      Vm with a root mean square error of 4.27% and a correlation coefficient of
      0.9992. For shocks delivered during diastole, the saturation of Vm is
      qualitatively reproduced even when the sodium and calcium channels are
      inactivated. Quantitative replication of the response to diastolic shocks is
      hindered by the choice of electroporation parameters (optimized for shocks
      delivered during the plateau) and differences in the membrane kinetics between
      model and experiment. The complex behavior of Vm during large shocks is due to a
      combination of electroporation, electrotonus, propagation, and active membrane
      kinetics. The modeling results imply that the experimentally observed saturation
      of Vm is due to electroporation of the lipid bilayer.

PMID- 9662152
TI  - A novel interpolation method for electric potential fields in the heart during
      excitation.
AB  - In mapping the electrical activity of the heart, interpolation of electric
      potentials plays two important roles. First, it permits the estimation of
      potentials in regions that could not be sampled or where signal quality was poor,
      and second, it supports the construction of isopotential lines and surfaces for
      visualization. The difficulty in developing robust interpolation techniques for
      cardiac applications lies in the abrupt change in potential in the vicinity of
      the activation wave front. Despite the resulting nonlinearities in spatial
      potential distributions, simple linear interpolation methods are the current
      standard and the resulting errors due to aliasing can be large if electrode
      spacing does not lie on the order of 0.5-2 mm--the thickness of the activation
      wave front. We have developed a novel interpolation method that is based on two
      observations specific to the spread of excitation in the heart: (1) that
      propagation velocity changes smoothly within a region large enough to contain
      several measurement electrodes and (2) that electrogram morphology varies very
      little in the neighborhood of each sample point except for a time shift in the
      potential wave forms. The resulting interpolation scheme breaks the interpolation
      of one highly nonlinear variable--extracellular potential--into two separate
      interpolations of variables with much less drastic spatial variation--activation
      time and electrogram morphology. We have applied this method to potentials
      originally recorded at 1.5 mm spacing and then subsampled at a range of densities
      for testing of the interpolation. The results based both on reconstruction of
      isopotential contour maps and statistical comparison showed significant
      improvement of this novel approach over standard linear techniques. The
      applications of the new method include improved determination of
      electrophysiological parameters such as spatial gradients of potential and the
      path of cardiac activation and recovery, estimation of electrograms at desired
      locations, and visualization of electric potential distributions.

PMID- 9662153
TI  - Mathematical modeling of the first inflation of degassed lungs.
AB  - The pressure-volume (P-V) relationship of degassed lungs during the first
      inflation is different from that in consecutive inflations. We developed a
      mathematical model of the P-V curve of the first inflation by assuming that (1)
      central airways are open leading to many subtrees of n generations that are
      initially closed; (2) an airway opens when inflation pressure reaches the opening
      threshold pressure of that segment; and (3) the opening threshold pressures do
      not depend on airway generation. In this model, airway opening occurs in cascades
      or avalanches. To test the model which contains only two parameters, n and a
      pressure, P(low), at which at least one subtree completely opens, we measured the
      first inflation P-V curves of 15 excised and degassed rabbit lungs. By fitting
      these data, we found that n=17+/-5, P(low)=23+/-4 cmH2O, and that there is a wide
      distribution of threshold pressures for airways with diameters <2 mm. Analysis of
      the P-V curve in a lung which was lavaged with a liquid of constant surface
      tension and in which airways are presumably open demonstrated that the
      distribution of threshold pressures is narrow, and hence no avalanches occur
      during inflation. We conclude that in normal lungs the first inflation is
      dominated by avalanche behavior of airway opening providing information on the
      global distribution of threshold pressures and the average site of airway
      closure.

PMID- 9662154
TI  - Solute washout experiments for characterizing mass transport in hollow fiber
      immunoisolation membranes.
AB  - The transport characteristics of immunoisolation membranes can have a critical
      effect on the design of hybrid artificial organs and cell therapies. However, it
      has been difficult to quantitatively evaluate the desired transport properties of
      different hollow fiber membranes due to bulk mass transfer limitations in the
      fiber lumen and annular space. An attractive alternative to existing
      methodologies is to use the rate of solute removal or "washout" from the annular
      space during constant flow perfusion through the fiber lumen. Experimental
      washout curves were obtained for glucose and a 10 kD dextran in two different
      hollow fiber devices. Data were analyzed using a theoretical model which accounts
      for convective and diffusive transport in the lumen, membrane, and annular space.
      The model was in good agreement with the experimental results and provided an
      accurate measure of the effective membrane diffusion coefficient for both small
      and large solutes. This approach should prove useful in theoretical analyses of
      solute transport and performance of hollow fiber artificial organs.

PMID- 9662155
TI  - 1997 Whitaker Distinguished Lecture: Models to solve mysteries in biomechanics at
      the cellular level; a new view of fiber matrix layers.
AB  - Three different fundamental cellular level transport models are presented to
      explore current or recently solved mysteries in what appear to be three unrelated
      problem areas: (i) Starling's hypothesis for lymph formation in the
      microcirculation; (ii) the cellular level transduction and transmission
      mechanisms for sensing and communicating mechanical strain in bone; and (iii) the
      growth of cellular level macromolecular leakage spots in the arterial intima and
      their relation to the formation of subendothelial liposomes. This trilogy of what
      appear to be unrelated problems is shown to have a common link, the thin layer of
      specialized matrix that cells produce at the surface of their plasmalemma
      membranes in part to regulate the water and solute transport that surrounds them.
      In each case unexpected model predictions have led to new hypotheses and the
      design of new experiments which have helped explain long-standing fundamental
      questions in biomechanics.

PMID- 9662156
TI  - Electrical signal transmission in a bone cell network: the influence of a
      discrete gap junction.
AB  - A refined electrical cable model is formulated to investigate the role of a
      discrete gap junction in the intracellular transmission of electrical signals in
      an electrically coupled system of osteocytes and osteoblasts in an osteon. The
      model also examines the influence of the ratio q between the membrane's
      electrical time constant and the characteristic time of pore fluid pressure, the
      circular, cylindrical geometry of the osteon, and key simplifying assumptions in
      our earlier continuous cable model (see Zhang, D., S. C. Cowin, and S. Weinbaum.
      Electrical signal transmission and gap junction regulation in a bone cell
      network: A cable model for an osteon. Ann. Biomed. Eng. 25:379-396, 1997). Using
      this refined model, it is shown that (1) the intracellular potential amplitude at
      the osteoblastic end of the osteonal cable retains the character of a combination
      of a low-pass and a high-pass filter as the corner frequency varies in the
      physiological range; (2) the presence of a discrete gap junction near a resting
      osteoblast can lead to significant modulation of the intracellular potential and
      current in the osteoblast for measured values of the gap junction coupling
      strength; and (3) the circular, cylindrical geometry of the osteon is well
      simulated by the beam analogy used in Zhang et al.

PMID- 9662157
TI  - Effect of fatiguing exercise on longitudinal bone strain as related to stress
      fracture in humans.
AB  - Muscular fatigue in the training athlete or military recruit has been
      hypothesized to cause increased bone strain that may contribute to the
      development of a stress fracture. Under normal circumstances, muscles exert a
      protective effect by contracting to reduce bending strains on cortical bone
      surfaces. In vivo strain studies in dogs show that muscle fatigue following
      strenuous exercise elevates bone strain and changes strain distribution. However,
      a similar experiment has yet to be performed in humans. The purpose of this work
      was to test the hypothesis in humans that strenuous fatiguing exercise causes an
      elevation in bone strain. It was also hypothesized that this elevation is greater
      in younger people than in older people due to the decline in muscle strength and
      endurance that normally occurs with age. To test these hypotheses, strain in the
      tibiae of seven human volunteers was measured during walking before and after a
      period of fatiguing exercise. Neither hypothesis was sustained. Post-hoc analysis
      of the strain data suggests that strain rate increases after fatigue with a
      greater increase in younger as opposed to older persons. Although not conclusive,
      this suggests that it is strain rate, rather than strain magnitude, that may be
      causal for stress fracture.

PMID- 9662158
TI  - Fluorescence and laser photon counting: measurements of epithelial [Ca2+]i or
      [Na+]i with ciliary beat frequency.
AB  - We describe a system we developed that enabled simultaneous measurements of
      either epithelial calcium ion concentration ([Ca2+]i) or sodium ion concentration
      ([Na+]i) with the ciliary beat frequency (CBF) in native ciliated epithelia using
      either Fura-2 (AM) or SBFI (AM) ratiometric fluorescence photon counting along
      with nonstationary laser light scattering. Studies were performed using native
      epithelial tissues obtained from ovine tracheae. The dynamic range of the laser
      light-scattering system was determined by a simulated light "beating" experiment.
      The nonstationary CBF was demonstrated by the time-frequency analysis of the raw
      photon count sequences of backscattered heterodyne photons from cultured and
      native epithelia. Calibrations of calcium and sodium ion concentrations were
      performed using the respective Fura-2 and SBFI impermanent salts as well as in
      native epithelia. The cumulative responses of 10(-6), 10(-5), and 10(-4) M
      nifedipine on [Ca2+]i together with the CBF as well as the cumulative responses
      of 10(-5), 10(-4), and 10(-3) M amiloride on [Na+]i together with the CBF were
      also determined. Nifedipine decreased [Ca2+]i but had no effect on CBF. Amiloride
      decreased [Na+]i and CBF. Stimulation of CBF corresponded with either an increase
      of [Na+]i or an increase of [Ca2+]i. Decreases of [Na+]i or substantial decreases
      of [Ca2+]i were associated with decreases in the CBF. These data demonstrate the
      utility of this system for investigating the regulatory mechanisms of
      intracellular ions dynamics and the CBF in native epithelia.

PMID- 9662159
TI  - A micromechanical model of lung tissue rheology.
AB  - The rheological properties of lung tissue are complex and nonlinear and
      contribute significantly to both the elastic and dissipative mechanical
      properties of the lung. Nevertheless, there remain large gaps in our
      understanding of precisely how the bulk rheological behavior of lung tissue is
      linked to the properties of its constituents and their interactions. In this
      paper a model is developed that attempts to provide such a link. The model
      consists of a sheet of randomly aligned fibers whose orientations are constantly
      changing due to thermal motion. When the sheet is suddenly stretched uniaxially,
      the fibers align themselves preferentially in the direction of strain. However,
      as a result of the continual thermal motion of the fibers, there is a net
      transfer of momentum between the fibers and the rest of the tissue. This produces
      a restoring force in the tissue sheet. The thermal motion also makes the fibers
      gradually revert back to a random orientation, so that the strain-generated
      stress within the tissue decays asymptotically to zero. It is shown that the
      behavior of this model closely approximates quasilinear viscoelasticity, in which
      the static stress-strain behavior is separable from the dynamic stress relaxation
      behavior.

PMID- 9662160
TI  - Quadratic phase coupling as a quantitative measure for the developing hippocampal
      formation.
AB  - This paper presents the bispectral analysis of the ontogeny of the hippocampal
      EEG recorded from the dentate gyrus and CA1, the primary sites that generate
      theta (theta) rhythm. The hippocampal EEG was collected during the vigilance
      state of rapid eye movement (REM) sleep of freely moving rats at 15, 30 and 90
      days of age. In previous studies we demonstrated through bispectral analysis that
      significant quadratic phase coupling (QPC) of the EEG exists in the hippocampal
      formation of CA1 and the dentate gyrus during REM sleep, primarily in the theta
      (4-11 Hz) frequency range. In the present study we have examined whether QPC can
      be used as an effective measure of development, i.e., maturation of the
      hippocampal subfields CA1 and the dentate gyrus. We found that as animals mature
      from the age of 15 to 90 days, the occurrence of nonlinear QPC activities moves
      from (6.25 Hz, 6 Hz) to (7 Hz, 7 Hz) at CA1 and (6 Hz, 6 Hz) to (7.5 Hz, 7.5 Hz)
      at the dentate gyrus, respectively. The results indicate that bispectral analysis
      provides an additional and important description of the frequency characteristics
      of the hippocampal EEG and that the QPC measure is also a useful index to
      quantify the shift in the hippocampal theta frequency as animals mature.

PMID- 9662161
TI  - Sensitivity distributions of impedance cardiography using band and spot
      electrodes analyzed by a three-dimensional computer model.
AB  - Impedance cardiography (ICG) offers a safe, noninvasive, and inexpensive method
      to track stroke volume estimates over long periods of time. Several modified ICG
      measurement configurations have been suggested where for convenience or improved
      performance the standard band electrodes are replaced with electrocardiogram
      electrodes. This report assesses the sensitivity of the conventional and three
      modified ICG methods in detecting regional conductivity changes in the simulated
      human thorax. The theoretical analyses of the measurement sensitivity employ the
      reciprocity theorem and the lead field theory with a highly detailed,
      anatomically accurate, three-dimensional computer thorax model. This model is
      based on the finite-difference element method and the U.S. National Library of
      Medicine's Visible Human Man anatomy data. The results obtained indicate that the
      conventional four-band ICG is not specifically sensitive to detect conductivity
      changes in the region of the heart, aortas, and lungs. Analyzed modified
      electrode configurations do not reproduce exactly the measurement sensitivity
      distribution of the conventional four-band ICG. Thus, although the signals
      measured with modified spot arrangements may appear similar to the four-band
      configuration, the distribution of the signal origin may not be the same.
      Changing from band to spot electrodes does not overcome the methodological
      problems associated with ICG.

PMID- 9662162
TI  - Role of cellular orientation in electrical coupling between gastrointestinal
      smooth muscle.
AB  - Electrical fields produced during depolarization as well as low resistance
      pathways through gap junctions have been proposed as electrical coupling
      mechanisms serving to coordinate electrical control activity in gastrointestinal
      smooth muscle. The differing orientations of the longitudinal and circular muscle
      layers offer many possible configurations for cells coupled by electrical fields.
      The boundary element method is used to investigate coupling, with respect to both
      gap junctions and field effects for ellipsoidal and cylindrical cells.
      Physiological considerations allow the possibility of aggregates of cells with
      coordinated electrical activity. The effect of multiple source cells on field
      coupling is also modeled. Results indicate that even small gap junctional
      conductances are effective for coupling of smooth muscle and that field coupling
      is most efficacious when the ellipsoidal cells are coupled side by side and when
      cylindrical cells are coupled end to end.

PMID- 9662163
TI  - Real-time measurement of lysis of mural platelet deposits by fibrinolytic agents
      under arterial flow.
AB  - An in vitro whole blood reperfusion model was employed to quantify: (a) initial
      rates of lysis of mural platelet deposits from flowing blood onto fibrin-coated
      surfaces and (b) plasmin-mediated consumption of plasma plasminogen and
      fibrinogen, by recombinant tissue-type plasminogen activator (rt-PA) and two t-PA
      variants, KHRR 296-299 AAAA (K-tPA) and T103N, N117Q, KHRR 296-299 AAAA (TNK
      tPA), at wall shear rates of either 500 or 1000 s(-1). K- and TNK-tPA are more
      fibrin-specific than rt-PA, and are also resistant to inactivation by plasminogen
      activator inhibitor-1 (PAI-1). At 500 s(-1), no agent showed significant lysis of
      mural platelet deposits on fibrin, even at concentrations as high as 10 microg/ml
      of blood. At 1000 s(-1), each agent demonstrated a dose-dependent lysis of mural
      platelet deposits, due to plasmin-mediated lysis of the fibrin substrate
      (fibrinolysis). The local concentration of thrombolytic agents close to the
      fibrin-coated surface is probably higher than the concentration of released PAI-1
      from the adherent and activated platelets. Hence, the initial rates of lysis
      achieved by K- and TNK-tPA were not significantly different from that by rt-PA,
      when each agent was tested at either 1 or 10 microg/ml of blood. However, TNK
      tPA, at 1 microg/ml, caused the most extensive lysis at the end of the 50 min
      reperfusion period (50% vs 29% and 17% by rt-PA and K-tPA, respectively). K- and
      TNK-tPA, at concentrations as high as 10 microg/ml of blood, caused plasminogen
      activation that was controlled by the natural plasmin inhibitors, and, thus, no
      proteolytic degradation of plasma fibrinogen (fibrinogenolysis). On the contrary,
      rt-PA at 1 microg/ml revealed slight fibrinogenolysis that became extensive at 10
      microg/ml. This study demonstrates the potential use of an in vitro model, that
      mimics the in vivo hemodynamic environment, in evaluating the performance of
      thrombolytic agents. The data suggest that: (a) adequate flow must accompany
      fibrinolysis for successful embolization, and (b) the TNK variant may lyse
      annular thrombi after recanalization, at least as efficiently as rt-PA does,
      while causing lesser defect of systemic hemostasis.

PMID- 9662164
TI  - Prediction of muscle recruitment and its effect on joint reaction forces during
      knee exercises.
AB  - This study examined the hypothesis that muscle recruitment of the tibiofemoral
      joint and joint reaction forces during isometric and isokinetic exercises depends
      on the existing degrees of freedom of the knee and the direction and type of
      external load applied during exercise. When three-dimensional knee joint rotation
      was considered (three degrees of freedom), antagonistic muscle activities were
      predicted using an inverse dynamic problem formulation and muscle modeling
      optimization procedures. The results showed that the antagonistic activities of
      flexors during knee flexion/extension exercise increased the joint compressive
      forces and decreased the anterior tibial shear forces. Comparison of different
      knee joint modeling assumptions indicated that modeling a single degree of
      freedom in flexion/extension for the knee will underestimate the antagonistic
      muscle function.

PMID- 9662165
TI  - Recycling isoelectric focusing and isotachophoresis.
AB  - Of all electrophoretic methods, isoelectric focusing offers the highest
      resolution and is best suited for preparative applications. Over the years,
      several instruments were developed for this purpose, all operating in free
      fluids, in the absence of gels or other supporting matrices. In such systems, the
      avoidance of gravity or electrically driven convections is essential. Successful
      stratagems for fluid control included rapid recycling or rotation, in combination
      with either fine porosity screens or narrow gaps between parallel plates. The
      most successful apparatus so far is the Rotofor, in which fluid is stabilized by
      combining horizontal rotation with fine porosity screen partitioning. Recycling
      isotachophoresis offers the potential of separating proteins at high
      concentration. A new concept of tangential electrophoresis is described. To
      optimize the use of these devices for protein separation, low molecular weight,
      biologically acceptable buffers of known composition are essential. The buffering
      system developed for this purpose comprises a series of binary buffers that cover
      the pH range in steps of 1 pH unit or less. The pH gradient can be custom
      designed and is of remarkable stability in operation.

PMID- 9662166
TI  - Continuous free-flow electrophoresis.
AB  - This review evaluates the literature on continuous free flow electrophoresis,
      published during the last four years. Its aim is to serve not only experts in the
      field but also newcomers, and, therefore, it also briefly describes the
      principles of the method and the techniques used, referring to fundamental papers
      published earlier. The actual commercial instrumentation is briefly outlined. A
      substantial part of this review is devoted to the optimization of the performance
      of this method. Finally, diverse applications of fractionations of charged
      species in solution, ranging from small ions to biological particles and cells,
      are surveyed.

PMID- 9662167
TI  - An isoelectrically trapped enzyme reactor operating in an electric field.
AB  - Membrane enzyme reactors constitute an attempt at integrating catalytic
      conversion, product separation and/or concentration and catalyst recovery into a
      single operation. Whereas conventional membrane reactors confine an enzyme, in a
      free form, to one side of a membrane by size exclusion, electrostatic repulsion,
      or physical or chemical immobilization onto an intermediate support (gel,
      liposome), the membrane reactor here described is shown to operate under an
      entirely new principle: enzyme confinement into an isoelectric trap located in a
      multicompartment electrolyzer operating in an electric field. Two isoelectric
      membranes, having pI values encompassing both the enzyme pI and the pH of its
      optimum of activity, act by continuously titrating the enzyme trapped inside,
      thus preventing it from escaping the reaction chamber. Charged products generated
      by the enzyme catalysis are continuously electrophoretically transported away
      from the reaction chamber and collected into other chambers stacked either
      towards the cathodic or anodic sides. In a urease reactor, ammonia is
      continuously harvested towards the cathode, thus allowing >95% substrate
      consumption with maintenance of enzyme integrity over much longer time periods
      than in a batch reactor. In a trypsin reactor, casein is digested and
      biologically active peptides are continuously harvested in a pure form into
      appropriate isoelectric traps. In a third example, pure D-phenylglycine is
      produced from a racemate mixture, via an acylation reaction onto a cosubstrate
      (the ester methyl-4-hydroxyphenyl acetate), brought about by the enzyme
      penicillin G acylase.

PMID- 9662168
TI  - Enantiomeric separation of methadone by cyclodextrin-based capillary and
      recycling isotachophoresis.
AB  - The separation of methadone enantiomers by cationic capillary isotachophoresis
      (CITP) and recycling isotachophoresis (RITP) having (2-hydroxypropyl)-beta
      cyclodextrin (OHP-beta-CD) as chiral selector in the leading electrolyte is
      described. Sodium acetate/acetic acid (pH between 4 and 5) served as leading
      electrolyte (catholyte) and acetic acid as terminator (anolyte). Complete
      separation of the enantiomers was obtained by CITP in a 50 microm internal
      diameter (ID) fused-silica capillary and in a 500 microm ID Teflon capillary. In
      the first approach, enantiomeric separation could be monitored via UV absorbance
      detection at low wavelength. With the second instrumental setup, an additional
      conductivity sensor permitted the visualization of the enantiomeric separation
      and the characterization of the buffer system employed. A 10 mM sodium
      acetate/acetic acid leading buffer of pH 4.3, containing 5 mM OHP-beta-CD, was
      found to provide best enantiomeric separation and was thus chosen for RITP. With
      RITP processing of a few mg of racemic methadone, partial separation of methadone
      enantiomers was obtained. R-(-)-methadone and S-(+)-methadone were found to be
      significantly (up to about 80%) enriched at the front and back side,
      respectively, of the isotachophoretic zone. The enantiomeric composition of
      methadone in the collected fractions was assessed by chiral capillary zone
      electrophoresis (CZE) and circular dichroism spectroscopy. CZE was found to
      represent a simple and efficient method for the determination of the enantiomeric
      excess, whereas the latter technology was noted to be the superior approach for
      properly characterizing fractions that contain similar amounts of the two
      enantiomers. Furthermore, chiral RITP and analysis of the collected fractions by
      circular dichroism spectroscopy is shown to be potentially useful for
      identification of single enantiomers in absence of pure chiral standards.

PMID- 9662169
TI  - Separation and characterization of humic acids and metal humates by
      electrophoretic methods.
AB  - A modified buffer for the separation of humic acids (HA) by capillary zone
      electrophoresis (CZE) was studied. The addition of hydroxycarboxylic acids to
      borate buffer makes a more efficient separation of HA possible. Two sharp peaks
      are obtained. Preparative isolation of these two fractions can be reached by
      applying the conditions used in CZE to free-flow electrophoresis (FFE). The
      fractions obtained were characterized by repetition of the CZE procedure. Also
      metal complexes of HA were investigated by electrophoretic methods. In the
      presence of metal cations, HA form stable complexes of different electrophoretic
      mobility. These complexes can be separated by free-flow isotachophoresis (FF
      ITP). The different fractions are analyzed by CZE, ultraviolet-visible and atomic
      absorption spectrometry. Significant changes in both the ITP-pattern of the FFE
      and the 'humic hump' in CZE demonstrate the influence of complexation on the
      macromolecules.

PMID- 9662170
TI  - Application of free-flow electrophoresis to the purification of trichosanthin
      from a crude product of acetone fractional precipitation.
AB  - The application of free-flow electrophoresis (FFE) to the purification of
      trichosanthin (TCS) from a crude product of acetone fractional precipitation was
      investigated. An electrophoresis technique, combining field step electrophoresis
      (FSE) and zone electrophoresis (ZE) to a one-step procedure, was optimized until
      a satisfactory purification factor (1.35), high resolution, and purity (>99%)
      were achieved. Testing several separation buffer systems revealed that a
      throughput of 14.2 mg/h can be obtained when the very basic TCS (pI 10.1) was
      dissolved and electrophoresed in a phosphate buffer system of pH 4. The purity of
      electrophoresed trichosanthin was proved by a variety of analytical methods, such
      as sodium dodecyl sulfate (SDS)-gel electrophoresis, capillary isoelectric
      focusing (CIEF), and sequencing of N- and C-termini. The high purity and large
      throughput achieved at low cost by using FFE indicates that this method can be
      employed for TCS purification.

PMID- 9662171
TI  - Counterbalancing hydrodynamic sample distortion effects increases resolution of
      free-flow zone electrophoresis.
AB  - On fractionation of highly heterogeneous protein mixtures, optimal resolution was
      achieved by forcing proteins to migrate through a preestablished pH gradient,
      until they entered a medium with a pH similar but not equal to their pIs. For
      this purpose, up to seven different media were pumped through the electrophoresis
      chamber so that they were flowing adjacently to each other, forming a pH gradient
      declining stepwise from the cathode to the anode. This gradient had a
      sufficiently strong band-focusing effect to counterbalance sample distortion
      effects of the flowing medium as proteins approached their isoelectric medium
      closer than 0.5 pH units. Continuous free-flow zone electrophoresis (FFZE) with
      high throughput capability was applicable if proteins did not precipitate or
      aggregate in these media. If components of heterogeneous protein mixtures had
      already started to precipitate or aggregate, in a medium with a pH exceeding
      their pI by more than 0.5 pH units, the application of interval modus and media
      forming flat pH gradients appeared advantageous.

PMID- 9662172
TI  - Automated free-solution isotachophoresis: instrumentation and fractionation of
      human serum proteins.
AB  - An automated free-solution isotachophoresis system (FS-ITP) for preparative
      fractionation of biopolymers is described, operated in a batch mode. The
      dimension of the separation chamber allows an up to 1200-fold higher sample load
      compared to separation in capillaries of 180 microm inner diameter as used in
      analytical capillary isotachophoresis (C-ITP). The preparative capacity of the
      system is within the milligram range. The method is fully compatible with
      analytical C-ITP, which is essential for preparative-scale isotachophoresis with
      regard to optimization of electrolyte systems and the search for suitable
      spacers. As a model application the fractionation of human serum proteins is
      reported. The collected fractions were analyzed by C-ITP and agarose gel
      electrophoresis.

PMID- 9662173
TI  - Purification of bioproducts by free-flow zone electrophoresis: choice of
      processing parameters.
AB  - Free-flow zone electrophoresis may be used to purify biological samples, due to
      differences in electrophoretic mobility, in absence of a matrix--most frequently
      a gel--thus enabling the biological integrity of even fragile molecules to be
      preserved. However, the process is more complicated than its principle suggests
      due to different transport phenomena interfering with electrophoretic migration,
      with the resultant separation depending both on separation effects and dispersive
      phenomena. The physical origin of the main effects involved was identified.
      Mathematical expressions were proposed to estimate the influence of the crescent
      effect and electrohydrodynamics on the process. In this paper, these equations
      are used to determine the minimum difference in electrophoretic mobility required
      for a separation to be achieved with respect to the processing parameters. A
      methodology is proposed which defines the conditions under which the difference
      in electrophoretic mobilities equals that calculated when considering the
      influence of dispersive phenomena. Optimized separations of the whey proteins
      lactoferrin and albumin, known to interact strongly, and the purification of a
      monoclonal antibody from a mouse ascitic fluid illustrate the approach.

PMID- 9662174
TI  - Application of free-flow electrophoresis for isolation and purification of
      proteins and peptides.
AB  - Free-flow electrophoresis (FFE) has been applied to the separation and
      purification of a variety of proteins and polypeptides: bee venom, tumor necrosis
      factor, interleukin-1beta, interferon-gamma and superoxide dismutase. FFE at
      constant pH and conductivity of the carrying buffer is shown to be efficient at
      various separation schemes. In some cases, the method allows us to obtain
      proteins with a purity of more than 90% at a productivity of 20-30 mg/h. An
      electrophoretic apparatus with a new, multi-sectional construction of the
      electrophoretic chamber and a system for cross-displacement of carrying buffer in
      the chamber is described.

PMID- 9662175
TI  - pH-regulated electroretention chromatography: towards a new method for the
      separation of proteins according to their isoelectric points.
AB  - The pH-dependent electroretention behavior of model proteins cytochrome c and
      ribonuclease A was studied in a hollow fiber arrangement, similar to that used in
      electrical field-flow fractionation. Field-induced immobilization of the proteins
      at the inner wall of the fiber was a function of the pH adjusted in the solution
      surrounding it, indicating that the pH inside the fiber lumen, relevant for
      protein migration, quickly equilibrates to the regulated value outside. A
      complete separation of the model proteins was achieved. Advantages of the
      principle as well as prospects for the development of a technique separating more
      than two protein species according to their isoelectric points are discussed.

PMID- 9662176
TI  - Isolation of peroxisome subpopulations from rat liver by means of immune free
      flow electrophoresis.
AB  - Immune free-flow electrophoresis (IFFE) has been applied to the separation of
      peroxisomes (PO). IFFE is a modification of antigen-specific electrophoretic cell
      separation (ASECS), and combines the advantages of electrophoretic separation
      with the high selectivity of an immune reaction. It differs from the latter in
      the pH of the electrophoresis buffer, which was shifted from the physiological
      range (ASECS) to the pI of IgG molecules (pH approximately 8.0), thus further
      decreasing the mobility produced by the binding of a specific antibody. This
      enhances the mobility differences between IgG-coupled particles and those
      nondecorated, with resultant improved separation. We have now succeeded in
      isolating different subpopulations of PO by applying IFFE to heavy, light, and
      post-mitochondrial fractions separated by differential centrifugation of a rat
      liver homogenate. The obtained PO subfractions differed in their composition of
      matrix and membrane proteins, as revealed by immunoblotting. This indicates that
      they indeed represent distinct subpopulations of rat hepatic PO.

PMID- 9662177
TI  - Free-flow electrophoresis for fractionation of Arabidopsis thaliana membranes.
AB  - Highly purified tonoplast and plasma membrane vesicles were isolated from
      microsomes of Arabidopsis thaliana by preparative free-flow electrophoresis. The
      most electronegative fractions were identified as tonoplast using nitrate
      inhibited Mg2+-ATPase as enzyme marker. The least electronegative fractions were
      identified as plasma membrane using glucan-synthase II, UDPG: sterol-glucosyl
      transferase, and vanadate-inhibited Mg2+-ATPase as enzyme markers. Other membrane
      markers, latent inosine-5'-diphosphatase (Golgi), NADPH-cytochrome-c reductase
      (endoplasmic reticulum) and cytochrome-c oxidase (mitochondria) were recovered in
      the fractions intermediate between tonoplast and plasma membrane. Immunoblot
      analysis of membrane fractions by antibodies directed against tonoplast and
      plasma membrane proteins confirmed the nature and the purity of the isolated
      membranes. The cytoskeletal protein actin, which was also identified by
      immunoblotting, was found to be specifically attached to the plasma membrane
      vesicles. The structural and functional integrity of the isolated membranes from
      Arabidopsis thaliana is discussed in the light of results obtained for the
      location of receptors and enzymes, or for the determination of ligand binding
      activity.

PMID- 9662178
TI  - Fluid-phase marker transport in rat liver: free-flow electrophoresis separates
      distinct endosome subpopulations.
AB  - Free-flow electrophoresis (FFE) was used to investigate the intracellular
      compartments involved in fluid-phase marker, fluoresceine isothiocyanate (FITC)
      dextran, transport in the isolated perfused rat liver. One to 2 min after uptake
      at 37 degrees C, FITC-dextran was found in endosomes with the same
      electrophoretic mobility as early sorting endosomes labeled either by the
      hepatocyte-specific marker asialoorosomucoid (ASOR) or by transferrin that enters
      all liver cells. Labeling at low temperature (16 degrees C) blocked transport of
      ASOR and dextran in early endosomes. With increasing internalization time (3-13
      min) at 37 degrees C, FITC-dextran-labeled compartments co-localized with late,
      ASOR-containing endosomes. Since localization of FITC-dextran in late
      transcytotic compartments was not observed upon FFE separation, it is concluded
      that the majority of internalized markers is directed to lysosomes. The FITC
      label did not account for the predominant lysosomal targeting of the dextran,
      since [3H]dextran-labeled endosomes exhibited an identical FFE pattern. Taken
      together, these data indicate that the fluid-phase marker dextran is transported
      through intracellular compartments with identical characteristics as endosome
      subcompartments of the receptor-mediated lysosomal route.

PMID- 9662179
TI  - Analysis of trypanosomal endocytic organelles using preparative free-flow
      electrophoresis.
AB  - In this paper we demonstrate the power of preparative free-flow electrophoresis
      (FFE) for the study of endocytosis by African trypanosomes. Endocytosis of
      extracellular macromolecules by these parasites occurs through a specialized
      region of the parasite called the flagella pocket. The uptake of fluid phase
      markers such as horseradish peroxidase (HRP) into the various compartments of the
      endocytic pathway of bloodstream forms of Trypanosoma brucei brucei was
      manipulated by regulating the external environment (e.g., by altering the
      temperature of incubation). The various subcellular compartments were then
      separated by free-flow electrophoresis (FFE) or isopycnic density gradient
      centrifugation and analyzed for marker uptake. At low temperatures, HRP was found
      predominantly in the flagellar pocket. Increasing the temperature resulted in a
      time-dependent uptake of HRP into more positively charged endosomal fractions.
      However, little HRP activity was detected in lysosomal compartments, suggesting
      that either HRP had not yet entered the lysosome or was degraded immediately upon
      entry. Through the use of FFE we were able to identify and analyze compartments
      of the endosomal pathway that were not possible to identify by density gradient
      centrifugation alone. Although the differences in FFE separation of the endocytic
      compartments as seen in HRP uptake were striking, the minor changes seen within
      the lysosomal system were more subtle, as depicted in the protease profiles. In
      conclusion, we show that preparative FFE is a powerful technique for the analysis
      and separation of flagellar pocket-derived membranes from other endosomal and
      lysosomal compartments of African trypanosomes.

PMID- 9662180
TI  - High performance density gradient electrophoresis of subcellular organelles,
      protein complexes and proteins.
AB  - A density gradient electrophoresis (DGE) apparatus (2.2 x, 14 cm) was constructed
      for the rapid separation of milligram quantities of proteins. By using binary
      buffers according to Bier (Electrophoresis 1993, 14, 1011-1018) proteins were
      rate-zonally separated in less than 60 min. Acidic proteins were separated in a
      pH 8.6, 56 microS/cm buffer, and basic proteins in a pH 5.4, 76 microS/cm buffer.
      Thus the A (pI 5.15) and B (pI 5.30) forms of beta-lactoglobulin as well as the
      sialylated glycoforms of apotransferrin were well separated at pH 8.6. The
      isoforms of myoglobin (pI 6.9 and 7.35, respectively), RNAse A (pI 9.45) and
      cytochrome c (pI 10.0) and lysozyme (pI 11) were separated at pH 5.4 within 80
      min. On a 7 cm DGE column, subcellular organelles derived from HeLa cells were
      separated in standard electrophoresis buffer (655 microS/cm) for 90 min at 10 mA.
      Using a new low conductivity buffer (193 microS/cm) 20 min was sufficient to
      separate late endosomes, lysosomes, endoplasmic reticulum, early endosomes,
      plasma membrane, clathrin-coated pits, proteasomes, and clathrin-coated vesicles
      within a single run directly from a postnuclear supernatant.

PMID- 9662181
TI  - Subcellular fractionation by organelle electrophoresis: separation of phagosomes
      containing heat-killed yeast particles.
AB  - Uptake of foreign material and its subsequent lysosomal degradation is an
      important function of macrophages. The mechanisms involved in the binding, uptake
      and delivery of such material to lysosomal organelles, are, however, poorly
      understood. Here we describe a method using organelle electrophoresis to study
      the uptake and trafficking of heat-killed yeast particles within murine
      macrophages. Such yeast particles, which were fluorescently labeled, could be
      readily detected in intact cells as well as in subcellular fractions. Organelle
      electrophoresis of a homogenate from macrophages that had internalized yeast
      particles resulted in the separation of yeast-containing organelles from most
      other subcellular membranes. In addition, this method was used to follow the
      kinetics of yeast particle transport within macrophages could be followed
      readily. Organelle electrophoresis may be a valuable tool for the analysis of
      phagocytosis.

PMID- 9662182
TI  - Preparation of Golgi subfractions with free-solution isotachophoresis: analysis
      of sphingomyelin synthesis in Golgi subfractions from rat liver.
AB  - A new displacement electrophoresis technique, termed free-solution
      isotachophoresis (FS-ITP) was used for the analysis of sphingolipid metabolism in
      Golgi subfractions. The discontinuous electrolyte system enables tissue-derived
      membrane vesicles to be separated and purified due to their polarity patterns in
      a mobility gradient. In this study total Golgi apparatus obtained from rat liver
      by discontinuous density gradient centrifugation was subfractionated by
      preparative FS-ITP, yielding enzymatically active cis-, medial-, and trans-Golgi
      subfractions. These membrane vesicles were assayed by the following established
      enzyme marker activities: NADH cytochrome c reductase (cis-Golgi), NADP
      phosphatase (medial-Golgi), and thiamine pyrophosphatase (trans-Golgi). The
      activity of phosphatidylcholine:ceramide phosphocholine transferase, a
      sphingomyelin synthesizing enzyme, is attributed to the cis- and medial-Golgi
      derived subfractions. Analysis of Golgi lipids revealed a decline in membranous
      ceramide along the cis- to trans-Golgi polarity axis. Furthermore, significant
      amounts of newly synthesized sphingomyelin and diacylglycerol are transferred
      from the medial/cis- to the trans-Golgi compartment. The FS-ITP system is well
      suited for micropreparative experimental applications, as demonstrated by studies
      on phosphatidylcholine:ceramide phosphocholine transferase activity in Golgi
      membrane vesicles of rat liver obtained by FS-ITP.

PMID- 9662183
TI  - Separation and microgram-scale isolation of sea urchin egg granules by
      electrophoresis in polyvinylpyrrolidone solution, using horizontal gel
      electrophoresis apparatus with fluorescence detector.
AB  - A homogenate of sea urchin (Lytechinus pictus) eggs rich in exocytotic membrane
      vesicles (granules) was subjected to analytical and preparative electrophoresis
      in the commercial automated horizontal gel electrophoresis apparatus (HPGE-1000,
      LabIntelligence, Belmont, CA) capable of intermittent scanning of the migration
      path, using buffered solutions of polyvinylpyrrolidone (PVP). The nonfluorescent
      granules were detected by "fluorescence reduction", i.e., a decrease of
      fluorescence intensity due to the absorbance and/or light scattering properties
      of the particle. Granules migrated at linear migration rates in buffers ranging
      from 0 to 2.5% PVP. Two bands were observed and optimally separated in 1.5% PVP
      solution. As shown by sodium dodecyl sulfate (SDS)-polypeptide patterns, the
      material recovered from the bands was qualitatively indistinguishable from the
      two major fractions A and C of granules previously separated by free-flow
      electrophoresis in the absence of polymer. Ferguson plot analysis failed to
      provide the sizes of the granules in view of the narrow PVP concentration range
      available for mobility measurement and the unavailability of chemically
      homogeneous size standards.

PMID- 9662184
TI  - Immuno-isolation of highly purified peroxisomes using magnetic beads and
      continuous immunomagnetic sorting.
AB  - Immuno-isolation is a powerful technique for the isolation of cells as well as
      subcellular organelle populations based on their antigenic properties. We have
      established a method for immuno-isolation of peroxisomes (PO) from both rat liver
      and the human hepatoblastoma cell line HepG2 using magnetic beads as solid
      support. A polyclonal antibody raised against the cytoplasmic C-terminal 10 amino
      acids of the rat 70 kDa peroxisomal membrane protein was covalently bound to
      magnetic beads (Dynabeads M-450). The coated beads were incubated with a light
      mitochondrial fraction and the organelle-bead complexes formed were separated by
      magnetic sorting in a free-flow system without pelleting the complexes during the
      isolation procedure. Scanning electron microscopy revealed decoration of beads
      with particles measuring 150-400 nm in diameter. The particles were identified as
      PO by catalase cytochemistry and biochemically by marker enzyme analysis, sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) as well as
      immunoblotting for specific detection of peroxisomal matrix, core and membrane
      proteins. The functional significance of PO in man is emphasized by the existence
      of inherited diseases such as the Zellweger syndrome in which intact PO are
      lacking, but peroxisomal remnants called "ghosts" are observed instead.
      Peroxisomal disorders are usually studied using skin fibroblast cell lines
      derived from afflicted patients and immuno-magnetic separation may prove
      particularly useful for the investigation of such cultured cells and for further
      elucidation of the pathogenesis of fatal peroxisomal disorders.

PMID- 9662185
TI  - Separation of viable from radiation-induced apoptotic lymphocytes by free-flow
      electrophoresis.
AB  - A human lymphocyte population undergoing apoptosis in vitro due to gamma
      irradiation was fractionated by free-flow electrophoresis in triethanolamine--Na
      acetate buffers, containing up to 50 mM NaCl, with pH 6.0, 7.2 and 8.5, made
      isotonic by addition of sucrose. As shown by a flow cytometric analysis of the
      eluate, the distribution of apoptotic lymphocytes is shifted to the range of
      higher electrophoretic mobilities relative to that of viable ones at pH 8.5,
      yielding cell fractions enriched in apoptotic cells by a factor of 3 to 5. The
      difference in rates of electrophoretic migration observed at a mildly alkaline pH
      but not at a neutral or mildly acidic one suggests that the surface of apoptotic
      lymphocytes is more acidic than that of viable ones.

PMID- 9662186
TI  - Characterization of a subpopulation of mouse red blood cells as preferential
      target for malarial invasion.
AB  - Cell electrophoresis was used to study a distinct subpopulation of murine red
      blood cells (RBC). These RBC are normally found in the spleen and bone marrow.
      They appear in the peripheral blood when mice are mildly bled or sucked by
      mosquitos. These cells have been characterized as having larger size, light
      density, lower electrophoretic mobility, and being more resistant to lysis with
      unsaturated fatty acids and in glycerol-containing medium than mature
      erythrocytes. All their features suggest that their differentiation status
      represents an intermediate stage between reticulocytes and adult RBC. In vitro
      Plasmodium invasion tests showed their increased sensitivity to invasion by the
      parasites. The extent of their spreading in the blood was found to be strain
      dependent, being more pronounced in C57B1/6 mice, highly susceptible to
      developing cerebral malaria after infection with Plasmodium berghei, as compared
      to Balb/c, a nonsusceptible strain of mice.

PMID- 9662187
TI  - Surface modification of superparamagnetic nanoparticles (Ferrofluid) studied with
      particle electrophoresis: application to the specific targeting of cells.
AB  - Colloidal aqueous suspension of superparamagnetic nanoparticles (9 nm in
      diameter) composed of maghemite (gamma Fe2O3) and forming an ionic ferrofluid in
      aqueous solution are covalently coupled with lectins, enzymes or antibodies,
      using specific thiol chemistry. The surface charge modifications of
      nanoparticles, caused by ligand coupling, were monitored by measuring their
      electrophoretic mobilities using laser-Doppler velocimetry. Particle
      electrophoretic mobility (PEM) changes are shown to correlate well with the
      amount of ligand fixed on the particles, as probed by its biological activity.
      The PEM method provides a useful tool to optimize ligand immobilization at the
      surface of nanoparticles, and may be advantageous when biological activity
      measurements are not convenient.

PMID- 9662188
TI  - Cell electrophoretic mobility and glycerol lysis of human erythrocytes in various
      diseases.
AB  - Using an automated cell electrophoresis system equipped with an image processor,
      we studied electrophoretic mobilities of erythrocytes of healthy donors and of
      patients suffering from systemic lupus erythematosus (SLE), rheumatoid arthritis
      (RA), hypergammaglobulinemia and diabetes mellitus (DM). On average, erythrocytes
      from SLE patients showed mean electrophoretic mobilities (EPM) which were
      significantly lower (p < 0.005) than the EPM of red blood cells of normal donors.
      Evaluation of mean EPM and standard deviations revealed that three groups of SLE
      patients could be distinguished regarding the electrophoretic behavior of their
      erythrocytes. Some patients had red blood cells with normal EPM, others had
      erythrocytes with significantly reduced EPM, and a third group appeared to have
      both kinds of erythrocytes. In addition, erythrocytes of various SLE patients
      showed enhanced resistance to lysis by glycerol and their membranes contained
      less quantities of band 3 proteins.

PMID- 9662189
TI  - Experimental study on temperature distribution within a wide-gap continuous free
      flow electrophoresis chamber.
AB  - The temperature distribution within a wide-gap (3 mm) continuous free-flow
      electrophoresis (CFFE) chamber was investigated by direct measurements. The walls
      of the chambers consisted of Plexiglas and thermocouples were used as temperature
      sensors. The study of different operating and heat dissipating conditions
      revealed that lateral temperature gradients arise in CFFE chambers in addition to
      an axial increase in temperature of 0.25 degrees C per Watt of electric power and
      per minute of residence time in the absence of cooling.

PMID- 9662190
TI  - Two doses of PMPA protect newborn macaques against oral simian immunodeficiency
      virus infection.
AB  - BACKGROUND: Simple and affordable intervention strategies are needed to reduce
      the rate of HIV transmission from mother to infant in developing countries.
      Simian immunodeficiency virus (SIV) infection of newborn rhesus macaques is
      considered to be a useful model of human pediatric HIV infection. OBJECTIVE: To
      investigate whether short-term 9-[2-(phosphonomethoxy)propyl]adenine (PMPA)
      administration can protect newborn rhesus macaques against perinatal SIV
      infection. DESIGN AND METHODS: Eight newborn macaques were inoculated orally with
      highly virulent SIVmac within the first 3 days of life. Four of these animals
      were untreated controls. The other four animals were given one dose of PMPA (30
      mg/kg subcutaneously) 4 h before oral SIV inoculation, and were then given a
      second and final dose of PMPA 24 h later. RESULTS: All four untreated control
      animals were persistently SIV-positive within 2 weeks after virus inoculation. In
      contrast, no virus could be detected in the four animals that received two doses
      of PMPA; these animals were seronegative and healthy at 10 months. CONCLUSIONS:
      Two doses of PMPA prevented SIV infection of newborn macaques. Our data suggest
      that short-term administration of PMPA to HIV-infected pregnant women at the
      onset of labor and to their newborns after delivery may reduce the rate of
      intrapartum HIV transmission.

PMID- 9662191
TI  - The role of a stromal cell-derived factor-1 chemokine gene variant in the
      clinical course of HIV-1 infection.
AB  - BACKGROUND: A G-to-A transition in the 3' untranslated region (UTR) of stromal
      cell-derived factor (SDF)-1 gene (SDF1-3'A) has recently been described, which in
      the homozygous state was associated with delayed disease progression. OBJECTIVE:
      To analyse the effect of the SDF-1 polymorphism on AIDS-free survival and
      survival after AIDS diagnosis, also in relation to viral phenotype. DESIGN:
      Retrospective longitudinal study among 344 homosexual HIV-1-infected men.
      RESULTS: A more rapid progression to AIDS (Centers for Disease Control and
      Prevention 1993 definition) was observed in SDF1-3'A/3'A subjects than in wild
      type (SDF1-wt/wt) subjects (relative hazard, 1.75; P = 0.07). Using death as an
      endpoint, accelerated progression was no longer observed (relative hazard, 0.93;
      P = 0.84), suggesting a late protective effect of the SDF1-3'A/3'A genotype.
      Indeed, survival after AIDS diagnosis was significantly delayed in SDF1-3'A/3'A
      subjects (relative hazard, 0.40; P = 0.02). No effect of the SDF1-3'A/wt genotype
      on disease progression was observed. Interestingly, a higher frequency of
      Kaposi's sarcoma was observed as the AIDS-defining event among SDF1-3'A/3'A
      (40.0%) and SDF1-3'A/wt (30.6%) subjects than in SDF1-wt/wt subjects (17.0%). At
      the end of the study the total frequency of syncytium-inducing (SI) HIV-1
      variants was lower in SDF1-3'A/3'A subjects (22.2%) than in SDF1-3'A/wt (32.5%)
      and SDF1-wt/wt subjects (40.5%), although not significantly. SDF-1 genotype did
      not influence the rate of evolution to SI HIV-1. Progression to AIDS after the
      emergence of SI HIV-1 was accelerated in SDF1-3'A/3'A subjects compared with the
      SDF1-wt/wt genotypic group (relative hazard, 4.04; P = 0.06). CONCLUSIONS: In our
      study group, homozygosity for a G-to-A transition in the 3' UTR of SDF-1 is
      associated with an accelerated progression to AIDS but a subsequent prolonged
      survival after AIDS diagnosis.

PMID- 9662192
TI  - Effect of HIV constructs containing protease-reverse transcriptase fusion
      proteins on viral replication.
AB  - OBJECTIVE: To determine whether disruption of the cleavage site between protease
      and reverse transcriptase (RT) or the HIV-1 frameshift site could yield trans
      dominant negative HIV-1 variants that interfere with wild-type viral replication.
      DESIGN: Residues at the cleavage site between the HIV-1 protease and RT coding
      regions were mutagenized to produce a protease-RT (PR-RT) fusion protein that was
      expressed in the context of a full-length provirus. The PR-RT cleavage site
      mutation was also combined with a read-through mutation at the frameshift site in
      order to overexpress the mutant Gag-Pol polyproteins. METHODS: COS-7 cells were
      transiently transfected with the mutant constructs to produce viruses harbouring
      the PR-RT fusion protein. In addition, we performed cotransfection studies in
      various cell types to analyze the inhibition of wild-type replication by the
      mutant constructs. RESULTS: Immunoblot analysis revealed that this novel mutation
      prevented cleavage between the two proteins and that both existed as a PR-RT
      fusion protein in each of cellular and viral lysates. While both the protease and
      RT components of this fusion protein remained functionally active, viruses
      containing the cleavage site mutation were less infectious in tissue culture than
      wild-type viruses produced by COS-7 cells. This defect was further pronounced
      when the cleavage site mutation between protease and RT was overexpressed as a
      consequence of an additional mutation that interfered with frameshifting.
      Cotransfection of COS-7 cells with the mutant constructs and wild-type HIV-1
      interfered with the replication of the latter and reduced the infectiousness of
      the virus particles produced. CONCLUSIONS: HIV-1 constructs harbouring a cleavage
      site mutation between protease and RT can probably act as trans-dominant negative
      mutants to interfere with wild-type viral replication.

PMID- 9662193
TI  - Synthetic full-length and truncated RANTES inhibit HIV-1 infection of primary
      macrophages.
AB  - OBJECTIVE: To determine the effect of beta-chemokines on HIV-1 infection of
      primary macrophages, and to search for chemokine derivatives devoid of biological
      effects but efficient at protecting CD4+ T lymphocytes and macrophages against
      HIV-1. DESIGN: Use of chemically synthesized molecules devoid of biological
      contaminants and monocyte-derived macrophages from healthy donors. METHODS: Full
      length RANTES was chemically synthesized together with three derivatives,
      truncated of seven, eight and nine amino acids at the amino-terminus ([8
      68]RANTES, [9-68]RANTES and [10-68]RANTES), which were tested for their
      biological activity and antiviral effects. RESULTS: Whereas full-length and
      truncated RANTES derivatives bound to beta-chemokine receptor CCR-5 with the same
      affinity as recombinant RANTES, the truncated forms were not chemotactic and
      acted as CCR-5 antagonists in this respect, although a partial agonist effect was
      noted on cell metabolism. Full-length RANTES and [8-68]RANTES protected T
      lymphocytes and macrophages from infection by HIV-1, although 10-fold higher
      concentrations of the truncated analogues were necessary to achieve the same
      effect as full-length RANTES. With regard to the effect of RANTES on HIV-1
      infection of primary macrophages, our results contrast with most previously
      reported data. CONCLUSION: These data indicate that through binding to CCR-5,
      truncated RANTES derivatives that are devoid of detectable biological effects may
      represent candidates as drugs to protect both lymphocytes and macrophages from
      HIV- 1.

PMID- 9662194
TI  - Rare mutations in a domain crucial for V3-loop structure prevail in replicating
      HIV from long-term non-progressors.
AB  - OBJECTIVE: To evaluate the role of the selective forces exerted by the host on
      the HIV-1 structures involved in viral entry. DESIGN AND METHODS: The V3 region
      of the env gene was analysed in cell-free HIV-1 RNA from 17 infected subjects: 11
      long-term non-progressors (LTNP) and six symptomless, typical progressor
      patients. To evaluate the potential biological significance of one of the rare
      variants detected in the LTNP, it was reproduced by recombinant PCR into a HIV-1
      molecular clone. RESULTS: The intrapatient divergence of the V3-loop sequences
      averaged 8.62% in LTNP and 5.29% in progressors, although LTNP displayed lower
      divergence from the clade B consensus than progressors (16.65 and 19.76%,
      respectively). The analysis of non-synonymous and synonymous substitutions
      indicated that selective pressure was exerted in this region in both LTNP and
      progressors. Individual peculiarities (unique and rare V3-loop variants) emerged,
      however, in most sequences from LTNP, and variants bearing mutations in a domain
      crucial for the V3-loop structure were more prevalent in LTNP (P = 0.0012). The
      pNL4-3-derived mutant reproducing a V3-loop variant detected in a LTNP was
      efficiently expressed upon transfection, but the mutant virus was nearly
      completely unable to infect CD4+ cell lines, activated primary peripheral blood
      lymphocytes, or monocyte-derived macrophages, suggesting that a defect impaired
      the entry phase of the replication cycle. CONCLUSIONS: The results indicate that
      host factors impose selective constraints on the evolution of the HIV-1
      structures involved in viral entry. In LTNP, these factors are likely to force
      the virus into attenuated variants.

PMID- 9662195
TI  - Impaired telomerase activity in uninfected haematopoietic progenitors in HIV-1
      infected patients.
AB  - BACKGROUND: Haematopoietic progenitor cells (HPC) of HIV-1-infected patients are
      severely compromised in their replication and clonogenic capacities, and show an
      enhanced propensity to apoptosis, despite the lack of productive or latent HIV-1
      infection. OBJECTIVE: To investigate telomerase enzyme levels in CD34+ HPC
      isolated from HIV-1-infected patients, because the absence of telomerase activity
      has been found to be correlated with a diminished replication potential. METHODS:
      Telomerase levels were measured by a PCR-based telomeric repeat amplification
      protocol. CD34+ HPC isolated from the peripheral blood of 11 HIV-1-infected
      patients were compared with CD34+ HPC isolated from peripheral blood (nine
      subjects) or bone marrow (six subjects) from 15 healthy donors. Telomerase levels
      were also studied in normal HPC after exposure to either gp120 or transforming
      growth factor (TGF)-beta1. RESULTS: CD34+ HPC isolated from either peripheral
      blood or bone marrow from healthy donors expressed a high level of telomerase
      activity. On the contrary, CD34+ HPC isolated from HIV-1-seropositive patients
      did not express any detectable telomerase activity in nine patients, and a
      clearly reduced enzymatic activity in two patients. Furthermore, telomerase
      activity in normal CD34+ HPC exposed to recombinant gp120 was significantly
      reduced, and to a higher extent than in CD34+ HPC exposed to recombinant TGF
      beta1. CONCLUSIONS: This is the first study to demonstrate severely impaired
      telomerase activity in uninfected CD34+ HPC isolated from HIV-1-infected
      patients. The mechanism underlying this impairment probably involves the
      interaction of HIV-1 envelope glycoprotein gp120 with the cell membrane. These
      results may add to our understanding of the pathogenesis of the lesion of the HPC
      compartment.

PMID- 9662196
TI  - Disease progression and survival following specific AIDS-defining conditions: a
      retrospective cohort study of 2048 HIV-infected persons in London.
AB  - OBJECTIVE: To assess the impact of specific AIDS-defining conditions on survival
      in HIV-infected persons, with emphasis on the effect of tuberculosis. METHODS: A
      retrospective cohort analysis of HIV-infected Africans and non-Africans attending
      11 specialist HIV/AIDS units in London enrolled for a comparison of the natural
      history of HIV/AIDS in different ethnic groups. RESULTS: A total of 2048 patients
      were studied of whom 627 (31%) developed 1306 different AIDS indicator diseases.
      Pneumocystis carinii pneumonia accounted for 159 (25%) of initial AIDS episodes
      and tuberculosis for 103 (16%). In patients with HIV disease, tuberculosis had
      the lowest risk [relative risk (RR), 1.11; 95% confidence interval (CI), 0.75
      1.63], and high-grade lymphoma had the highest risk (RR, 20.56; 95% CI, 2.70
      156.54) for death. For patients with a prior AIDS-defining illness, the
      development of subsequent AIDS indicator diseases such as Pneumocystis carinii
      pneumonia (RR, 1.18; 95% CI, 0.77-1.83) and tuberculosis (RR, 1.36; 95% CI, 0.76
      2.47) had the best survival, and non-Hodgkin's lymphoma had the worst survival
      (RR, 9.67; 95% CI, 1.26-74.33). Patients with tuberculosis had a lower incidence
      of subsequent AIDS-defining conditions than persons with other initial AIDS
      diagnoses (rate ratio, 0.47; 95% CI, 0.37-0.59). CONCLUSIONS: Considerable
      variation exists in the relative risk of death following different AIDS-defining
      conditions. The development of any subsequent AIDS-defining condition is
      associated with an increased risk of death that differs between diseases, and
      this risk should be considered when evaluating the impact of specific conditions.
      Like other AIDS-defining conditions, incident tuberculosis was associated with
      adverse outcome compared with the absence of an AIDS-defining event, but we found
      no evidence of major acceleration of HIV disease attributable to tuberculosis.

PMID- 9662197
TI  - Prevalence of genotypic resistance to nucleoside analogues in antiretroviral
      naive and antiretroviral-experienced HIV-infected patients in Spain.
AB  - OBJECTIVE: To determine the prevalence of genotypic resistance to nucleoside
      analogues (NA) in a large group of HIV-infected individuals in Spain, some of
      whom had no previous treatment with antiretroviral drugs (antiretroviral-naive)
      and some of whom had such experience (antiretroviral-experienced). SETTING: Cross
      sectional study in out-patient clinics in three reference hospitals for HIV/AIDS
      located in Barcelona, Madrid and Seville, Spain. PATIENTS AND METHODS: Primary
      mutant genotypes were examined in plasma HIV RNA collected from 150
      antiretroviral-naive subjects, half in 1993 and the other half in 1997.
      Furthermore, drug resistance mutations were analysed in plasma collected from
      another 150 antiretroviral-experienced patients who had received 2 NA for longer
      than 1 year, either in sequence as monotherapy or as combination therapy. A line
      probe assay was used for recognizing mutations conferring resistance to
      zidovudine (ZDV), didanosine (ddI), zalcitabine (ddC), and lamivudine (3TC). A
      point-mutation nested-PCR assay was used for examining a codon 151 mutation
      associated with multiple drug resistance. RESULTS: One or more mutations
      associated with primary resistance to NA were seen in 10 antiretroviral-naive
      (13.3%) patients in 1993 and in nine (12%) in 1997. In all but two cases, they
      were associated with ZDV resistance. In contrast, all but six (96%) of the
      antiretroviral-experienced subjects harboured drug-resistant mutant viruses. The
      codon 184 mutation (associated with resistance to 3TC) was detected in 92% of
      patients treated with 3TC, but also in 18% of those treated with only ddI or ddC.
      The codon 215 mutation was found in 67.3% of patients who had been exposed to
      ZDV; the codon 69 mutation was found in 15% of patients treated with ddC; and the
      codon 74 mutation was found in only 7.2% of patients treated with ddI. Finally,
      the codon 151 multidrug resistant mutation was found in four (2.7%) of 150
      patients with a long-term exposure to NA. CONCLUSIONS: Overall, the prevalence of
      drug-resistant HIV-1 genotypes was 12.7% in antiretroviral-naive patients, most
      of whom had ZDV-resistant mutants. There is no evidence of an increase during the
      last 5 years. However, multidrug-resistant HIV genotypes are currently
      circulating in Spain.

PMID- 9662198
TI  - Chemokines and receptors in HIV encephalitis.
AB  - BACKGROUND: Chemokines are involved in the migration of leukocytes and have been
      implicated in several inflammatory diseases of the central nervous system. Some
      of their receptors have been proposed to mediate HIV infection. OBJECTIVE: To
      determine changes in chemokine and receptor expression in HIV encephalitis, and
      to determine whether upregulation leads to recruitment of infected monocytes
      across the blood-brain barrier and participates in HIV neuropathology. METHODS:
      Immunocytochemistry and double-label immunofluorescent laser confocal microscopy
      was performed with antibodies to chemokines and their receptors on brain tissues
      from patients who died with or without HIV encephalitis. In vivo distribution was
      compared with in vitro cultures of human neuroglial cells. RESULTS: The beta
      chemokines monocyte chemotactic protein-1, macrophage inflammatory protein
      1alpha, and RANTES were detected on brain macrophages. Their presence was
      associated with the histopathological signs of HIV encephalitis. The alpha
      chemokines IP-10 (10 kDa inflammatory protein) and interleukin-8 were expressed
      by astrocytes in all tissues, including controls. Presence of the CXC-chemokine
      receptor (CXCR)-4 was seen on brain macrophages/microglia, neurons, and
      astrocytes. CC-Chemokine receptor (CCR)-5 was detected only on
      macrophages/microglia. CCR-3 and CCR-1 were expressed by macrophages and
      endothelial cells. In vitro studies examining the presence of CCR-3, CCR-5, and
      CXCR-4 on human brain cell cultures demonstrated abundant neuronal and microglial
      expression. CONCLUSIONS: Expression of a variety of chemokines and receptors was
      shown to be increased in HIV encephalitis brain tissues particularly in areas of
      neuroglial reaction. The expression pattern supported their involvement in the
      recruitment of inflammatory infiltrates and formation of microglial nodules.
      Presence of chemokine receptors on neurons may be involved in the pathogenesis of
      neurologic damage in AIDS patients.

PMID- 9662199
TI  - Haptoglobin polymorphism, iron metabolism and mortality in HIV infection.
AB  - BACKGROUND: Three phenotypes of the antioxidant protein haptoglobin are known: Hp
      1-1, Hp 2-1 and Hp 2-2. OBJECTIVES: To investigate the outcome of HIV infection
      according to haptoglobin type. DESIGN AND METHODS: Haptoglobin phenotypes were
      determined using starch gel electrophoresis in serum obtained from 653 HIV
      infected Caucasians in the AIDS reference centers of Gent (n = 184), Antwerp (n =
      309), and Luxembourg (n = 160). Survival was compared between haptoglobin types
      using Kaplan-Meier curves. Plasma HIV-1 RNA was quantified by reverse
      transcriptase PCR. Serum iron, transferrin saturation, ferritin, and vitamin C
      were assayed to evaluate iron-driven oxidative stress in 184 HIV-infected
      patients and 204 controls. RESULTS: The haptoglobin type distribution amongst the
      patients (17.6% Hp 1-1, 49.9% Hp 2-1, 32.5% Hp 2-2) corresponded to that of the
      controls. Kaplan-Meier curves showed a higher mortality for the Hp 2-2 group (P =
      0.0001; adjusted mortality risk ratio, 1.78; 95% confidence interval, 1.25-2.54).
      Median survival time was 11.0 years (Hp 1-1 and Hp 2-1) versus 7.33 years (Hp 2
      2). Plasma HIV-1 RNA levels prior to antiviral therapy and their increase over 1
      year were highest in Hp 2-2 patients (P = 0.03 and 0.003, respectively). The Hp 2
      2 type was associated with higher serum iron, transferrin saturation, and
      ferritin levels and with low vitamin C concentrations. Furthermore, ferritin
      concentrations were higher in HIV-infected patients than in controls (P <
      0.0001). CONCLUSION: HIV-infected patients carrying the Hp 2-2 phenotype show a
      worse prognosis, which is reflected by a more rapid rate of viral replication (in
      the absence of antiviral treatment). They also accumulate more iron and oxidize
      more vitamin C, suggesting that less efficient protection against
      haemoglobin/iron-driven oxidative stress may be a direct mechanism for
      stimulating viral replication.

PMID- 9662200
TI  - Efficacy of melaleuca oral solution for the treatment of fluconazole refractory
      oral candidiasis in AIDS patients.
AB  - OBJECTIVE: To evaluate the efficacy of melaleuca oral solution in AIDS patients
      with fluconazole-resistant oropharyngeal candida infections. DESIGN: A
      prospective, single center, open-labeled study. SETTING: A university-based inner
      city HIV/AIDS clinic. PATIENTS: Thirteen patients with AIDS and oral candidiasis
      documented to be clinically refractory to fluconazole, as defined by failure to
      respond to a minimum of 14 days of > or = 400 mg fluconazole per day.
      Additionally, patients had in vitro resistance to fluconazole, defined by minimal
      inhibitory concentrations of > or = 20 microg/ml. INTERVENTIONS: Patients were
      given 15 ml melaleuca oral solution four times daily to swish and expel for 2-4
      weeks. MAIN OUTCOME MEASURES: Resolution of clinical lesions of oral
      pseudomembranous candidiasis lesions. Evaluations were performed weekly for 4
      weeks and at the end of therapy for clinical signs of oral candidiasis.
      Quantitative yeast cultures were performed at each evaluation. RESULTS: A total
      of 13 patients were entered into the study, 12 were evaluable. At the 2-week
      evaluation, seven out of 12 patients had improved, none were cured, and six were
      unchanged. At the 4-week evaluation, eight out of 12 patients showed a response
      (two cured, six improved), four were non-responders, and one had deteriorated. A
      mycological response was seen in seven out of 12 patients. A follow-up evaluation
      2-4 weeks after therapy was discontinued revealed that there were no clinical
      relapses in the two patients who were cured. CONCLUSIONS: Melaleuca oral solution
      appears to be effective as an alternative regimen for AIDS patients with
      oropharyngeal candidiasis refractory to fluconazole.

PMID- 9662201
TI  - Is AIDS a floating point between HIV seroconversion and death? Insights from the
      Tricontinental Seroconverter Study.
AB  - OBJECTIVE: To investigate the significance of the time from seroconversion to
      AIDS (incubation time) and other covariates for survival from AIDS to death.
      METHODS: In survival analysis, survival from AIDS to death was compared for
      different categories of length of incubation time adjusted and unadjusted for
      other covariates, and significant predictors for survival from AIDS to death were
      investigated. RESULTS: Survival after AIDS was not affected by the incubation
      time in univariate as well as in multivariate analyses. Predictive factors for
      progression from AIDS to death were age at seroconversion, type of AIDS
      diagnosis, and CD4 cell count at AIDS. The relative hazard for age at
      seroconversion increased 1.38-fold over 10 years. Men with a CD4 cell count at
      AIDS of <130 x 10(6)/l had a twofold higher risk in progression to death than men
      with higher CD4 cell counts. Persons diagnosed with lymphoma had a sixfold higher
      risk of progression to death than persons with Kaposi's sarcoma or opportunistic
      infections. CONCLUSIONS: The incubation time as well as other factors before AIDS
      did not affect survival after AIDS. Survival from AIDS to death can be predicted
      by data obtained at the time of AIDS diagnosis, such as type of diagnosis, age
      and CD4 cell count. AIDS seems to be a significant point in progression to death,
      and not just a floating point between infection and death affected by prior
      factors for persons who did not receive effective therapy and did not have long
      incubation times.

PMID- 9662202
TI  - Comparative prevalence, incidence and short-term prognosis of cervical squamous
      intraepithelial lesions amongst HIV-positive and HIV-negative women.
AB  - OBJECTIVE: To investigate the impact of HIV infection on the prevalence,
      incidence and short-term prognosis of squamous intraepithelial lesions (SIL), in
      a prospective study with 1-year follow-up. METHODS: Between 1993 and 1995, 271
      HIV-positive and 171 HIV-negative women at high risk of HIV infection were
      recruited, 365 (82.6%) of whom completed the 1-year follow-up. The women
      underwent a Papanicolaou smear test at inclusion and at 6 and 12 months. Human
      papillomavirus (HPV) was detected at inclusion by Southern blot and PCR. RESULTS:
      The SIL prevalence ranged from 7.5% for HIV-negative to 31.3% for HIV-positive
      women with CD4 cell counts < 500 x 10(6)/l (P < 0.001). Other factors associated
      independently and significantly with SIL prevalence were HPV-16, 18, 33 and
      related types, HPV-31, -35, -39 and related types, lifetime number of partners,
      younger age, past history of SIL and lack of past cervical screening. The SIL
      incidence ranged from 4.9% in HIV-negative women to 27% in HIV-positive women
      with CD4 cells < 500 x 10(6)/l (P < 0.001). Progression from low- to high-grade
      SIL during follow-up was detected in 38.1% of HIV-positive women with CD4 cells <
      or = 500 x 10(6)/l but in no HIV-negative nor HIV-positive women with CD4 cells >
      500 x 10(6)/l. HPV-16, 18, 33 and related types were also associated with higher
      incidence of SIL and progression from low- to high-grade SIL. CONCLUSION: HIV
      induced immunodeficiency is associated with high prevalence, incidence and
      persistence/progression of SIL. A pejorative influence of HIV infection without
      marked immunodeficiency is less clear. HIV-positive women with SIL may thus
      benefit from early treatment when a useful immune response is still present.

PMID- 9662203
TI  - Population effects of preventive and therapeutic HIV vaccines in early- and late
      stage epidemics.
AB  - OBJECTIVE: To evaluate the population effects of potential preventive and
      therapeutic vaccines in early- and late-stage epidemics in a population of
      homosexual men. METHODS: An epidemic model was used that simulated the course of
      the epidemic for a population of homosexual men in San Francisco, California.
      Vaccine programs were evaluated by the number of cases of HIV averted, the effect
      on the prevalence of HIV, and by the gain in quality-adjusted life years (QALY)
      for the total population. RESULTS: In the model, a preventive vaccine prevented
      3877 cases of HIV infection during a 20-year period, reduced the projected
      prevalence of HIV infection from 12 to 7% in a late-stage epidemic, and gained
      15,908 QALY. A therapeutic vaccine that did not affect the infectivity of vaccine
      recipients increased the number of cases of HIV infection by 210, resulted in a
      slight increase in the prevalence of HIV infection from 12 to 15% in a late-stage
      epidemic, and gained 8854 QALY. If therapeutic vaccines reduced infectivity,
      their use could produce net gains of QALY in the population that were similar to
      gains from the use of preventive vaccines. In an early-stage epidemic, the
      advantage of a preventive vaccine program relative to a therapeutic vaccine
      program was markedly enhanced. CONCLUSIONS: Both preventive and therapeutic
      vaccine programs provided substantial benefit, but their relative merit depended
      on which outcome measures were assessed. Evaluation of HIV vaccine programs based
      solely on cases averted or on prevalence of HIV in the population underestimates
      the benefit associated with therapeutic vaccine programs. The effect of a
      therapeutic HIV vaccine on the epidemic outcomes depended markedly on whether the
      therapeutic vaccine reduced the infectivity of the vaccine recipient. The
      relative merits of preventive and therapeutic vaccines depend on the stage of the
      epidemic. Field vaccine trials should evaluate correlates of infectivity, such as
      HIV viral load. HIV vaccine implementation strategies should be tailored to the
      dynamics of the epidemic in specific populations.

PMID- 9662204
TI  - Cost-effectiveness of post-exposure prophylaxis following sexual exposure to HIV.
AB  - OBJECTIVES: To assess the cost-effectiveness, relative to other health-related
      interventions in the U.S., of post-exposure prophylaxis (PEP) following potential
      HIV exposure through sexual contact with a partner who may or may not be
      infected, and to compare the relative cost-effectiveness of dual- and triple
      combination PEP. METHODS: Standard techniques of cost-utility analysis were used
      to assess the cost-effectiveness of PEP with a four-week regimen of zidovudine
      and lamivudine, or zidovudine, lamivudine, and indinavir. Due to a lack of
      empirical data on the effectiveness of PEP with combination drug regimens, the
      analysis assumed that combination PEP was no more effective than PEP with
      zidovudine alone. The main outcome variable is the cost per quality-adjusted life
      year (QALY) saved by the program. RESULTS: Providing PEP to a cohort of 10,000
      patients who report receptive anal intercourse with a partner of unknown HIV
      status (who is assumed to be infected with probability equal to 0.18) would
      prevent about 20 infections, at an average net cost of about US$ 70,000 per
      infection averted. The cost-utility ratio, US$ 6316 per QALY saved, indicates
      that PEP is highly cost-effective in this instance. Moreover, triple-combination
      PEP would need to be about 9% more effective than dual-combination PEP for the
      addition of indinavir to the regimen to be considered cost-effective. Prophylaxis
      following receptive vaginal exposure is cost-effective only when it is nearly
      certain that the partner is infected; PEP for insertive anal and vaginal
      intercourse does not appear to be cost-effective. CONCLUSIONS: From a purely
      economic standpoint, PEP should be restricted to partners of infected persons
      (e.g., serodiscordant couples), to patients reporting unprotected receptive anal
      intercourse (including condom breakage), and possibly to cases where there is a
      substantial likelihood that the partner is infected. Providing PEP to all who
      request it does not appear to be an economically efficient use of limited HIV
      prevention and treatment resources.

PMID- 9662205
TI  - HIV-1 diversity in Romania.
AB  - OBJECTIVES: To evaluate the prevalence and the dynamics of HIV-1 subtypes in
      Romanian adults and children, and to investigate the origins of the nosocomial
      epidemic. DESIGN: A total of 1000 serum and plasma samples, from adults (n = 579)
      and children (n = 421) who were diagnosed as being HIV-1-infected during 1990
      1997 in 39 of the 41 Romanian districts, were serotyped. Viral DNA was isolated
      from blood samples of 84 patients and the viruses were genotyped. METHODS:
      Serotyping was performed with a peptide subtype-specific enzyme immunoassay
      (SSEIA), based on in vitro competition for antibody binding between the
      representative V3 peptides of the different clades (A-F). Proviral HIV-1 DNA was
      genotyped by heteroduplex mobility assay or by sequence analysis of the C2-V3 env
      region. RESULTS: SSEIA showed that 93% of the samples from horizontally infected
      children were serotype F, 1% were serotype B, and the remaining 6% were
      uninterpretable. In vertically infected children, 74% of strains were serotype F,
      10% were serotype A, 3% were serotype B, and 3% were serotype E. Serotype F was
      also the dominant subtype in adults (68%), but serotypes A, B, C, D and E were
      also detected. SSEIA gave indeterminate results in 7% of cases. A strong
      correlation (90%) between serotyping and genotyping for subtype F was found.
      Analysis of the relative incidence of the different serotypes over a 7-year
      period (1990-1997) showed a stable distribution. CONCLUSIONS: Subtype F largely
      dominates the epidemiology of HIV-1 infection in both children and adults in
      Romania, although other major subtypes are present. The predominance of subtype F
      in Romania may be a future potential source of HIV-1 variability in Europe.

PMID- 9662206
TI  - Association between HIV-1 infection and miscarriage: a retrospective study.
      DIANAIDS Collaborative Study Group. Diagnosi Iniziale Anomalie Neoplastiche AIDS.
AB  - OBJECTIVE: To determine the role of HIV-1 infection on miscarriage, we compared
      the obstetric histories of a cohort of HIV-1-infected and uninfected Italian
      women. DESIGN: Retrospective study. METHODS: The study participants were women
      (with at least one reproductive event) with HIV-1 infection or HIV-1-negative
      sharing the same exposure modalities; all women were attending a network of 16
      infectious disease units in 12 Italian cities. Trained interviewers used a
      standard questionnaire to collect information on obstetric history [i.e., number
      of pregnancies, pregnancy outcome (live birth, spontaneous or induced abortion)
      and time of occurrence of these events (i.e., year of birth)]. The association
      between spontaneous abortion and HIV-1 status at the time of pregnancy was
      evaluated. RESULTS: The analysis included 272 women and accounted for 480
      pregnancies (217 in HIV-infected women, 132 in uninfected women and 131 in women
      with undefined HIV status) and 60 miscarriages (23 in HIV-infected women, 22 in
      uninfected women and 15 in women with undefined HIV status). We estimated an
      adjusted odds ratio of 1.67 between spontaneous abortion and HIV-1 infection.
      CONCLUSIONS: We observed a 67% increase in risk of spontaneous abortion among HIV
      1-infected women compared with HIV-1-negative women. This result should be
      considered in the counselling and management of women with HIV-1 infection who
      are of reproductive age.

PMID- 9662207
TI  - An outbreak of multidrug-resistant tuberculosis involving HIV-infected patients
      of two hospitals in Milan, Italy. Italian Multidrug-Resistant Tuberculosis
      Outbreak Study Group.
AB  - OBJECTIVE: To describe an outbreak of multidrug-resistant tuberculosis (MDR-TB),
      amongst HIV-infected patients, spread from one hospital in Milan to another.
      DESIGN: Descriptive epidemiological investigation and molecular typing. METHODS:
      All cases identified by intensive case-finding were described in terms of
      clinical characteristics, previous nosocomial exposure to an infectious MDR-TB
      patient, previous stays in other institutional settings where exposure to MDR-TB
      could have occurred, and restriction fragment length polymorphism (RFLP) pattern.
      RESULTS: Between October 1991 and July 1995, 116 cases of MDR-TB were identified
      (85 at hospital A and 31 at hospital B). A single case patient, infected at
      hospital A, introduced the strain into hospital B. Eighty-two of the 92 strains
      available for fingerprinting revealed an identical pattern; 10 strains had unique
      RFLP patterns. Nosocomial exposure to an infectious MDR-TB patient was
      ascertained for 39 of the 56 patients with the 'outbreak' RFLP strain at hospital
      A (69.6%) and for 24 of the 26 patients at hospital B (92.3%). The median
      duration of exposure was 32 days at hospital A and 40 days at hospital B. For
      eight patients with the outbreak strain, exposure was determined to have probably
      occurred in other hospitals, in the community or in prison. CONCLUSIONS: This is
      the largest nosocomial outbreak of MDR-TB reported in Europe. Exposure to MDR-TB
      cases in other institutions caring for HIV-infected patients probably contributed
      to the spread of this epidemic. Strict control measures should be immediately
      adopted in order to prevent the spread of TB amongst HIV-infected patients in
      institutional settings in Europe.

PMID- 9662208
TI  - Upregulation of Fas ligand secretion in non-lymphopenic stages of HIV-1
      infection.

PMID- 9662209
TI  - Expression of the human herpesvirus 8-encoded viral macrophage inflammatory
      protein-1 gene in Kaposi's sarcoma lesions.

PMID- 9662210
TI  - HIV-1 diversity in heterosexual population in Slovakia, Ukraine and the Czech
      Republic.

PMID- 9662211
TI  - The epidemiological evolution of HIV-1 subtypes B and E among heterosexuals and
      injecting drug users in Thailand, 1992-1997.

PMID- 9662212
TI  - Naturally occurring decreased susceptibility of HIV-1 subtype G to protease
      inhibitors.

PMID- 9662213
TI  - Virological treatment failure of highly active antiretroviral therapy in an
      unselected cohort of HIV-infected patients.

PMID- 9662214
TI  - Virological failure and adherence to antiretroviral therapy in HIV-infected
      patients.

PMID- 9662215
TI  - Therapeutic advantage of hydroxyurea and didanosine combination therapy in
      patients previously treated with zidovudine.

PMID- 9662216
TI  - Nevirapine-induced hepatitis treated with corticosteroids?

PMID- 9662217
TI  - Protease inhibitors do not increase the CD4+ cell count in HIV-uninfected
      individuals.

PMID- 9662218
TI  - Ninth International Congress on Echocardiography: clinical cardiology.
      Introduction.

PMID- 9662219
TI  - Technologic advances in cardiology: the obsession for the clinician of the twenty
      first century.

PMID- 9662220
TI  - Assessing the relation between coronary reflow and myocardial reflow.
AB  - Since the recognition that prompt reperfusion of the infarct-related artery
      decreases mortality after acute myocardial infarction (MI), we have been
      interested in optimizing therapeutic regimens to accelerate the establishment of
      infarct-related artery patency. Although the major endpoint of many angiographic
      trials has been the acquisition of a patent infarct-related artery, this may not
      correlate with actual tissue perfusion because of the no-reflow phenomenon. With
      myocardial contrast echocardiography (MCE), we assessed the success of myocardial
      reperfusion at the microvascular level in patients with an acute anterior MI. We
      documented that 21% of the study patients exhibited Thrombolysis in Myocardial
      infarction (TIMI) grade 2 flow after coronary angioplasty, and all of them showed
      substantial "no reflow" on MCE. Conversely, no reflow was observed on MCE in only
      16% of patients with TIMI grade 3 flow. Early TIMI grade 3 flow resulted in a
      significantly better left ventricular functional outcome compared with those with
      TIMI grade 2. In view of microvascular perfusion, TIMI grade 2, despite the
      absence of coronary obstruction, cannot be regarded as successful reperfusion.
      Our study, using a Doppler guidewire probe, documented the specific coronary flow
      pattern in patients with TIMI grade 2. Patients with TIMI grade 3 flow exhibited
      systolic antegrade flow followed by the predominant diastolic flow. TIMI grade 2
      flow represented features of a to-and-fro coronary flow velocity pattern. This
      latter is characterized by (1) the abnormal retrograde flow in the early systole;
      (2) the reduction in the systolic antegrade flow; and (3) the rapid deceleration
      of the diastolic flow velocity. This pattern would be explained by an increase in
      vascular impedance and a decrease in myocardial blood volume.

PMID- 9662221
TI  - Echocardiography in the coronary care unit: diagnostic and prognostic impact in
      comparison with clinical and other indicators.
AB  - The clinical arena in which we must consider the role of echocardiography is
      characterized by 2 fundamental findings: (1) most patients with chest pain and
      suspected acute myocardial infarction (MI) do not present diagnostic
      electrocardiograms; and (2) an early and correct diagnosis is necessary to match
      the patient with the most adequate treatment. Echocardiography may be very useful
      in the coronary care unit, allowing a correct diagnosis of ischemic heart disease
      when electrocardiography is unclear, even before the rise of cardiac enzymes is
      detected. It may also play a role in decision-making for thrombolytic therapy. In
      addition, echocardiography provides useful information for early risk
      stratification. In fact, although high-risk patients are well identified by
      simple clinical or instrumental variables (i.e., Killip classification, enzymatic
      data, blood-gas analysis, electrocardiogram, etc.), most patients (>60%) are
      identified as low risk, and several subjects classified into the low-risk groups
      have a poor prognosis and are not detected using a single variable. In our
      experience, 2-dimensional echocardiography was able to further stratify between
      patients of low-risk classes. Therefore, echocardiography plays an important role
      in the early stratification of acute MI patients, especially in those without
      signs or symptoms of heart failure.

PMID- 9662222
TI  - Clinical impact of echocardiography in prognostic stratification after acute
      myocardial infarction.
AB  - Risk stratification is mandatory in the management of the postinfarction period.
      The identification of high-risk patients, on the basis of clinical data
      (recurrent angina, overt heart failure, etc.), is quite easy, whereas
      stratification of uncomplicated subjects needs an accurate noninvasive strategy.
      In the last 20 years, echocardiography has been gaining an increasing role,
      allowing increasingly precise evaluation of infarct size. This detection of the
      extent of infarct size has a definite prognostic value. Since 1980, we have
      observed that a dysfunctioning left ventricular myocardium >40% marked patients
      with a poor prognosis. These observations are most important in asymptomatic
      infarct patients, in whom clinical features may not reflect the amount of left
      ventricular dysfunction. Our recent results on a large series of patients with
      acute myocardial infarction (MI) without overt heart failure have shown that the
      extension of wall motion abnormalities at 2-dimensional (2D) echocardiography was
      highly predictive of cardiac death or new coronary events in a 3-year follow-up
      (univariate analysis; p <0.0005). Echocardiography also plays an important role
      in detecting postinfarct ischemia, as seen by its wide use during stress tests.
      In our experience, the response to exercise echocardiographic testing has a high
      prognostic value. In fact, in our series, univariate analysis (Kaplan-Meier)
      showed that the best predictors of coronary events were the number of markers of
      ischemia during exercise (p <0.00001), the work load (p <0.00001), a positive
      exercise echo (p <0.0005), and the echo score at rest (p <0.0005). Multivariate
      analysis (Cox) confirmed these data: number of markers of ischemia: odds ratio
      (OR) 4.45, 95% confidence interval (CI) 1.5-13.1; work load: OR 2.46, CI 1.3-4.5;
      positive exercise echo OR 1.88, CI 1.1-3.2. Thus, serial echocardiography
      together with predischarge stress echocardiography is recommended for risk
      stratification after acute MI. In particular, in thrombolytic-treated patients,
      echo examinations allow the detection of functional recovery of viable reperfused
      myocardium whereas stress echo may show exercise-induced worsening in the region
      supplied by the infarct-related vessel, a predictor of a higher rate of coronary
      events.

PMID- 9662223
TI  - Prognostic value of detection of myocardial viability using low-dose dobutamine
      echocardiography in infarcted patients.
AB  - Revascularization can improve ventricular function in patients with viable
      myocardium, but whether and how the presence of viable myocardium affects
      prognosis of infarcted patients is still far from clear. Thus, 202 patients (173
      men, 59 +/- 9 years old) with a previous or recent myocardial infarction (MI) and
      regional asynergies underwent low-dose dobutamine echocardiography (5-15
      microg/kg per min) to assess myocardial viability and were followed for a period
      of 16 +/- 11 months after revascularization (89 patients) or medical therapy (113
      patients). Four groups of patients were defined: (1) patients with viability,
      revascularized (n = 64); (2) patients with viability, treated medically (n = 52);
      (3) patients without viability, revascularized (n = 25); and (4) patients without
      viability, treated medically (n = 61). Of these patients, 45 (23%) patients
      suffered 57 cardiac events: 18 cardiac deaths (9%), 7 MIs, 12 unstable angina, 9
      heart failures, and 11 new revascularization procedures. Patients with viability,
      revascularized, experienced a slightly lower event rate (22%) compared with
      patients with viability, treated medically, patients without viability, treated
      medically and patients without viability, revascularized (29%, 31%, and 36%,
      respectively; p = not significant [NS]). The frequency of events was then
      evaluated in those 108 patients with an ejection fraction < or =33%, in whom 14
      cardiac deaths occurred: the incidence of cardiac death was slightly lower in
      patients with viability, revascularized (3/37, 8%) than in the patients with
      viability, treated medically (4/26, 15%), patients without viability,
      revascularized (2/11, 18%), or patients without viability, treated medically
      (5/34, 15%) (p = NS). Nonfatal cardiac events were significantly fewer (p <0.05)
      in patients with viability, revascularized (8%) and in patients without
      viability, treated medically (6%) than in patients with viability, treated
      medically and patients without viability, revascularized (27%). In infarcted
      patients with severe left ventricular dysfunction, the presence of viable
      myocardium, if left unrevascularized, leads to further events. On the contrary,
      in the absence of myocardial viability, revascularization could lead to a worse
      prognosis than medical therapy.

PMID- 9662224
TI  - Myocardial contrast echocardiography in the evaluation of viable myocardium after
      acute myocardial infarction.
AB  - Successfully reopening the infarct-related artery after acute myocardial
      infarction (MI) is currently achieved more frequently than before due to
      efficient therapeutic strategies, including new thrombolytic drugs and
      percutaneous transluminal coronary angioplasty. Successful reopening does not
      necessarily mean reperfusion; in fact the "no-reflow" phenomenon can occur. This
      phenomenon is due to functional and anatomic alterations, including
      microcirculation. Experimental and clinical studies have demonstrated that
      microvascular integrity is a fundamental prerequisite for ensuring viability
      after an acute MI. Often, studies have also shown that myocardial contrast
      echocardiography is a technique capable of detecting functional and anatomic
      conditions of microcirculation after ischemic reperfusion, and thus myocardial
      contrast echocardiography can be used for viability detection after acute MI.

PMID- 9662225
TI  - The complex relation between myocardial viability and functional recovery in
      chronic left ventricular dysfunction.
AB  - Preserved myocardial viability and recurrent symptomatic ischemia are the most
      widely accepted criteria indicating that coronary revascularization should take
      place in patients with postischemic left ventricular dysfunction. However, the
      presence of viable myocardium within the infarct zone does not necessarily imply
      recovery of function after coronary revascularization. The complex relation
      between the extent of transmural necrosis and the degree of residual perfusion
      within the infarct area plays an important role. However, independently of
      functional recovery, cell viability may have important clinical implications,
      since it may improve long-term prognosis by attenuating left ventricular
      remodeling processes. Several different methods are used to detect hibernating
      myocardium. Mounting evidence suggests that thallium-201 scintigraphy is most
      sensitive in identifying tissue viability, whereas dobutamine echocardiography is
      most specific in predicting functional recovery after revascularization. In
      between, myocardial contrast echocardiography is the only technique able to
      evaluate the microvascular integrity that is a condition sine qua non for both
      cell viability and later functional recovery. Combined information derived from
      these 3 different approaches might be considered as the best way to understand
      how the combination of contractile, viable but noncontractile, and dead tissue
      affect resultant function and prognosis.

PMID- 9662226
TI  - Postextrasystolic potentiation echocardiography in predicting reversible
      myocardial dysfunction by surgical coronary revascularization.
AB  - Sustained inotropic stimulation, such as dobutamine infusion, has the potential
      to cause an additional contractile deterioration in viable but chronically
      hypoperfused and dysfunctioning myocardium, by inducing ischemia.
      Postextrasystolic potentiation (PESP) represents a potent inotropic stimulus
      without risk of provoking ischemia, as it is instantaneous. In this study, we
      assessed the role of PESP-echocardiographic examination in predicting the
      recovery of regional contractility after coronary revascularization. We examined
      105 consecutive patients with multivessel coronary artery disease who were
      candidates for bypass surgery; 79 were included in this prospective study.
      Preoperative reversibility of contractile dysfunction in asynergic myocardial
      regions was determined by PESP, with a coupling interval of 500 msec decreasing
      to 300 msec, with a progressive decrease by 10 msec. The examination was
      accompanied by continuous 2-dimensional (2D) echocardiographic monitoring. The
      assessed sensitivity and specificity were 92% and 87%, respectively; the
      predictive accuracy was 90%. These results demonstrated that PESP
      echocardiography is a useful and cost-effective method for identifying viable
      myocardium in patients undergoing myocardial revascularization.

PMID- 9662227
TI  - Contrast echocardiography: review and future directions.
AB  - Recent developments and advances in contrast echocardiography have been made to
      improve the diagnosis and evaluation of cardiac structures and function. By
      coupling new developments in acoustic instrumentation with new contrast agents,
      information that was previously difficult or impossible to gather by standard 2
      dimensional echocardiography can now be obtained. Numerous studies have been
      published confirming the advantages of using contrast during echocardiographic
      studies, particularly with stress testing and myocardial perfusion. This review
      aims to summarize (1) the various contrast agents that are available or being
      developed; (2) factors that have been found to affect the strength of enhanced
      signals; (3) the new developments in instrumentation that improve the ability of
      scanners to differentiate echo contrast from cardiac tissue; and (4) the
      documented and possible future uses of contrast echocardiography.

PMID- 9662228
TI  - New modalities of regional and global left ventricular function analysis: state
      of the art.
AB  - Study of left ventricular (LV) regional and global function represents a main
      point of the cardiologic evaluation. This article presents an overview of the
      state of the art in quantitative analysis of ventricular wall motion and
      describes the different techniques available in clinical settings; we also
      present the personal experience of the authors in comparing conventional 2
      dimensional (2D) echocardiography with other recently developed, more
      sophisticated techniques. Conventional 2D echocardiography mainly depends on the
      operator's ability. Moreover, the physiologic regional pattern of myocardial wall
      motion in different segments of left ventricle is still not completely known as
      well as the heart's rotational and translational movements. Qualitative and
      quantitative transesophageal echocardiography allows a better and more accurate
      evaluation of regional wall motion, and improves the on-line border detection
      feasibility even in patients with poor transthoracic echocardiographic window.
      The automated system for on-line endocardial border detection, color kinesis, and
      the power Doppler are, at the moment, promising techniques. Using magnetic
      resonance imaging as a "gold standard" for the study of global and regional left
      ventricular function, the investigators describe personal experiences with tissue
      Doppler imaging and a new computerized system for tissue Doppler images
      postprocessing analysis.

PMID- 9662229
TI  - In vitro studies of a new thrombus-specific ultrasound contrast agent.
AB  - Ultrasound is used as a primary diagnostic technique for the detection of deep
      venous thrombosis. The purpose of this study is to describe the development of a
      new thrombus-specific ultrasound contrast agent: The linear hexapeptide (lysine
      glutamine-alanine-glycine-aspartate-valine) was synthesized and coupled to a
      lipid moiety. The targeted lipid was then incorporated into the lipid blend for
      the contrast agent Aerosomes (ImaRx, Tucson, AZ, USA). The lipid blend was used
      to entrap perfluorobutane microbubbles. The microbubbles were sized and studied
      in vitro for acoustic stability, binding to blood clot, and ultrasound
      enhancement in vitro of blood clot. The results showed the mean size of the
      specific ultrasound contrast agent (MRX-408) was about 2.0 microm. The
      microbubbles appeared as smooth spherical structures. Microscopy showed that the
      targeted bubbles bound to blood clot whereas control, nontargeted bubbles did not
      bind to blood clot. In vitro acoustic study showed similar stability of the
      microbubbles compared with control microbubbles. The targeted microbubbles
      enhanced blood clot in vitro whereas nontargeted microbubbles did not enhance
      clot. Thus this promising new thrombus-specific ultrasound contrast agent could
      potentially improve detection of thrombosis by ultrasound and might be useful for
      distinguishing between new and old thrombosis. In vivo studies are in progress.

PMID- 9662230
TI  - Clinical application of exercise stress echocardiography: supine bicycle or
      treadmill?
AB  - Although exercise stress echocardiography is currently used to evaluate coronary
      artery disease (CAD) patients, the best exercise methodology is still undefined.
      The objectives of the study were: (1) to compare supine bicycle stress
      echocardiography (SBSE) and treadmill in the evaluation of CAD; and (2) to
      define, in normal subjects, the different behavior of factors determining MVO2
      with treadmill and SBSE. We selected 10 male patients with CAD (group A), and 10
      male control subjects (group B). Each patient underwent SBSE and treadmill
      testing in random order. We studied heart rate, systolic blood pressure, heart
      rate x systolic blood pressure, and end-diastolic and end-systolic volume
      indexes. In group A, we also studied wall motion score index (according to the
      American Society of Echocardiography) and in group B, systolic blood pressure/end
      systolic volume index. The results were as follows: Group A: SBSE resulted in
      significantly lower work load, heart rate, and significantly higher systolic
      blood pressure, heart rate x systolic blood pressure, end-diastolic volume index,
      end-systolic volume index, and wall motion score index. SBSE showed wall motion
      abnormalities in each patient, whereas treadmill did not detect wall motion
      abnormalities in 4 patients (3 single-vessel; 1 multivessel); of the other 6
      patients, 2 showed a lower wall motion score index and 4 did not show any
      difference in left ventricle kinetics with the 2 methodologies of exercise. Mean
      acquisition time for postexercise images was 72 +/- 6 seconds. Group B: SBSE
      resulted in lower work load, heart rate, heart rate x systolic blood pressure,
      systolic blood pressure/end-systolic volume index, and higher end-diastolic
      volume index and end-systolic volume index. Systolic blood pressure was similar
      with SBSE and treadmill testing. In conclusion, our experience suggests SBSE is a
      highly accurate diagnostic tool for evaluating CAD compared with treadmill
      testing; the maximum cardiovascular performance can be achieved with lower values
      of heart rate, suggesting the echo test is more feasible. Treadmill testing could
      lose important information about the existence, extension, and location of CAD;
      in contrast, SBSE detects even small, quickly reversible wall motion
      abnormalities.

PMID- 9662231
TI  - Magnetic resonance imaging evaluation of myocardial perfusion.
AB  - Noninvasive qualitative/quantitative assessment of myocardial perfusion is
      considered to be fundamental in the management of known and suspected coronary
      artery disease patients, as shown by the widespread utilization of thallium-201-
      and technetium-99m-labeled agents in myocardial single-photon emission computed
      tomography (SPECT) scintigraphy for diagnostic as well as prognostic purposes.
      Recently, the availability of subsecond ultrafast magnetic resonance imaging
      (MRI) sequences (FLASH, TurboFLASH, EPI) has provided new avenues for assessing
      myocardial perfusion by MRI in conjunction with contrast-agent bolus
      administration (contrast-enhanced first-pass MRI). MRI contrast agents can be
      classified into relaxation agents (T1 "positive") and susceptibility agents (T2
      star [T2*] "negative"). All the commercially available MRI contrast agents used
      in clinical practice are relaxation agents employing the T1 shortening effect of
      metal ions like gadolinium (paramagnetism), thus producing a tissue signal
      intensity increase on T1-weighted images (positive enhancement). On the other
      hand, T2* agents induce mainly susceptibility effects, i.e., rapid dephasing of
      spins with resultant signal loss on T2*-sensitive sequences (negative
      enhancement). Unfortunately, both relaxation and susceptibility agents are, by
      definition, "extracellular" contrast media, as they rapidly diffuse into the
      interstitial space, thus hampering the simple application of indicator-dilution
      kinetics for myocardial perfusion assessment. Blood pool agents are therefore
      needed to obtain predictable relations between the concentration of contrast
      medium in the myocardium and the change in signal intensity. In addition, newer
      MRI techniques for tissue perfusion quantitation have been recently reported,
      based on blood-sensitive sequences, thus without intravenous contrast
      administration.

PMID- 9662232
TI  - Imaging of the distal left anterior descending coronary artery by transthoracic
      color-Doppler echocardiography.
AB  - Two-dimensional echocardiography evaluates the effect of myocardial ischemia on
      left ventricular wall motion, but a direct measure of coronary flow by this
      method is still lacking. The aim of the present study is to evaluate the efficacy
      of new, high-resolution ultrasound equipment designed to image by color Doppler
      transthoracic echocardiography the epicardial and intramural coronary vessels. We
      have studied 33 consecutive patients in apical projections, to detect by color
      Doppler > or = 1 segments of the middle-distal tract of the left anterior
      descending coronary artery. In 25 of 33 patients (76%), the middle-distal tract
      of the left anterior descending coronary artery was imaged by color Doppler. In
      15 of 33 patients (46%), the periapical tract of the left anterior descending was
      imaged along with its perforating branches. In 2 of 4 patients who had coronary
      artery bypass grafting, the anastomosis between the left internal mammary artery
      and the left anterior descending coronary artery was imaged. Once the coronary
      artery was imaged, pulsed Doppler was used to measure coronary blood flow
      velocity at rest. Peak and mean flow velocity, as well as the deceleration time
      (msec) and deceleration rate (cm/sec2), were measured on the diastolic phase of
      the Doppler tracing. In all 25 patients, it was possible to measure by pulsed
      Doppler the coronary flow velocity pattern characterized by a typical prevalent
      diastolic component. Peak diastolic flow velocity was 50 +/- 17 cm/sec and mean
      diastolic flow velocity was 37 +/- 12 cm/sec. The deceleration time was 916.2 +/-
      429.1 msec and the deceleration rate was 86.3 +/- 69.3 cm/sec2. The Doppler
      pattern of the grafted mammary artery was different from the native mammary flow.
      This new noninvasive imaging technique of the coronary arteries promises to
      expand the field of diagnostic and experimental echocardiography and brings new
      insight into the pathophysiology of ischemic heart disease.

PMID- 9662233
TI  - Multiplane transesophageal echocardiography and stroke.
AB  - Transesophageal echocardiography (TEE) is considered a basic tool in the
      diagnostic and follow-up evaluation of stroke patients, since up to 40% of
      cerebral ischemic events are presumed to have a cardiac origin. TEE offers a
      superior resolution of the posterior cardiac structures, such as left atrium and
      appendage and atrial septum, as well as of the aorta. By means of TEE, evidence
      has accumulated that some cardiovascular abnormalities (left-sided thrombi,
      tumors and vegetative lesions, complicated plaques of the aortic arch) are
      associated with ischemic stroke. Nevertheless, some issues remain unresolved.
      Will exclusion of atrial thrombus by multiplane TEE preclude embolism after
      cardioversion of atrial fibrillation? If anticoagulation before and after
      cardioversion is needed to provide adequate protection against embolism, will TEE
      be indicated in all patients? Moreover, can the detection of spontaneous echo
      contrast or enlarged and hypokinetic left atrial appendage in atrial fibrillation
      modify the therapeutic strategy? Is atrial septal aneurysm (ASA) a real embolic
      source, particularly when a right-to-left shunt is not associated? Considering
      the high prevalence of patent foramen ovale (PFO) in normal subjects, how can we
      identify patients at higher risk of embolism? Furthermore, methodologic points
      have to be taken into account when we analyze data from the literature. First,
      most studies are retrospective; a sole prospective study demonstrated that
      atherosclerotic plaques >4 mm thick in the aortic arch are significant predictors
      of recurrent brain infarction and other cardiovascular events in patients > or
      =60 years of age. Second, the association between the aforementioned cardiac
      abnormalities (mainly ASA and PFO) and cardiogenic embolism is biased by the
      patient-enrollment criteria used in those studies so that their pathogenetic role
      has not yet been established. Prospective studies with the enrollment of
      appropriate control groups will be necessary to define what can be considered a
      marker of embolic risk; the diagnosis "cardiogenic embolism" will not be a
      definitive diagnosis in most cases.

PMID- 9662234
TI  - Anatomic M-mode: a new technique for quantitative assessment of left ventricular
      size and function.
AB  - To overcome the limitations of conventional M-mode echocardiography, a new
      technique referred to as anatomic M-mode has been recently developed. This
      technique is based on postprocessing of digitally acquired two-dimensional (2D)
      cineloops, and allows the operator to position one or multiple independent M-mode
      cursors freely on the 2D images. Initial clinical data show that anatomic M-mode
      can increase the reproducibility and accuracy of standard M-mode measurements of
      the left ventricle. Also, this quantitative technique has the potential to
      improve assessment of left ventricular wall motion and thickening, and could be
      particularly useful in providing objective measures during stress
      echocardiography.

PMID- 9662235
TI  - Assessment of left ventricular dyssynergy by color kinesis.
AB  - Color kinesis is a new echocardiographic technique based on acoustic
      quantification. It has been developed to facilitate the ability to identify
      contraction abnormalities and has been incorporated into a commercially available
      ultrasound imaging system. The potential of this technique to improve the
      qualitative and quantitative assessment of wall motion abnormalities is
      described. Evaluation of color-encoded images allows detection of decreased
      amplitude of endocardial motion in abnormally contracting segments as well as a
      shorter time of endocardial excursion in segments with severely decreased motion.
      Compared with off-line quantitative studies, color kinesis has the advantage to
      be used on-line, without time-consuming manual tracing of endocardial boundaries.
      In addition, a single end-systolic color image contains the entire picture of
      spatial and temporal contraction and can be digitally stored and retrieved. In
      patients with proven coronary artery disease, color kinesis had a sensitivity of
      88%, a specificity of 77%, and an overall accuracy of 86% in identifying the
      presence of segmental dysfunction. The practical application of color kinesis
      might be to improve our ability to distinguish normal from hypokinesis, something
      that has always been difficult in clinical echocardiography. Segmental analysis
      of color kinesis images allows objective detection of dobutamine-induced regional
      wall motion abnormalities in agreement with conventional visual interpretation of
      the corresponding 2-dimensional views. A method for objective assessment of wall
      dynamics during dobutamine stress echocardiography would be of particular
      clinical value, because these images are even more difficult to interpret than
      conventional echocardiograms. Quantitative assessment of diastolic function may
      allow objective evaluation of segmental relaxation abnormalities, especially
      under conditions of pharmacologic stress testing. Acquisition of color kinesis
      images during dobutamine stress echocardiography, both transthoracic and
      transesophageal, may facilitate the assessment of hybernating but viable
      myocardium and enhance the sensitivity in the detection of coronary artery
      disease.

PMID- 9662236
TI  - Role of intravascular ultrasound in the evaluation of mechanisms of coronary
      interventions and restenosis.
AB  - Intravascular ultrasound (IVUS) has emerged from being a research tool to
      becoming an intrinsic part of modern invasive cardiology. The main reason is its
      ability to obtain "in vivo" microanatomy. For the first time it is possible to
      base decisions not only on lumenograms but also on vessel wall assessment. The
      intervention-associated potential of IVUS includes the ability to allow optimal
      device selection, i.e., rotablators in calcified lesions or atherectomy devices
      in large plaque burden. The effects of percutaneous transluminal coronary
      angioplasty (PTCA) on vessel-wall morphology can be studied in great detail and
      the effect on luminal gain can be assessed almost on-line. Several groups have
      showed that the residual plaque area, even after angiographically successful
      PTCA, still lies in the range of 60%. A significant reduction of this percentage
      may influence long-term outcome after PTCA. Minimal luminal areas and residual
      plaque area after PTCA seem to be an indicator of restenosis, whereas the
      presence or absence of dissections seem to be less predictive. The main mechanism
      of restenosis after PTCA is vessel shrinkage, not intimal hyperplasia.
      Intravascular monitoring of stent expansion led to high-pressure stent deployment
      with a significant increase in postprocedural luminal diameters and finally the
      ability to withhold anticoagulation in patients with optimal stent deployment.

PMID- 9662237
TI  - Three-dimensional echocardiography: clinical relevance and application.
AB  - Three-dimensional (3D) echocardiography has recently become a practical reality.
      It is now practicable to perform 3D echocardiography using transthoracic and
      transesophageal acoustic windows both in adults and children. The unique image
      projections that 3D echocardiography yields appear to have enormous potential for
      displaying intracardiac anatomy in exquisite detail. An important aspect of 3D
      echocardiography is its ability to supply accurate quantitative data without the
      use of geometric assumptions. In particular, coupled to contrast ultrasound
      agents, 3D echocardiography could be valuable in the assessment of myocardial
      perfusion abnormalities. Early clinical experience suggests that 3D
      echocardiography is likely to play a valuable role in the evaluation of various
      cardiac disorders, especially in cardiac surgery. In this section, we will review
      the use of volume-rendered 3D echocardiography in the diagnosis and assessment of
      cardiac disorders with particular emphasis on the clinical application of this
      new methodology.

PMID- 9662238
TI  - Three-dimensional echocardiographic assessment of the extension of dysfunctional
      mass in patients with coronary artery disease.
AB  - Two-dimensional (2D) echocardiographic estimation of infarcted mass is limited by
      having only a few selected nonparallel views for data analysis. Volume-rendered
      three-dimensional (3D) echocardiography may be able to overcome the above
      limitations, because it uses multiple, parallel 2D images to derive quantitative
      data. Previous experimental studies demonstrated that 3D echocardiography is an
      accurate and reproducible method to assess dysfunctional mass. To estimate the
      accuracy of 3D echocardiography in humans, we evaluated 10 patients who had a
      single myocardial infarction. All patients underwent 2D and 3D echocardiography
      using the transesophageal approach, and contrast (gadolinium) magnetic resonance
      imaging (MRI), considered a reference standard for infarcted tissue detection.
      The mean extent of dysfunctional mass by MRI was 28 +/- 13 g and by 3D
      echocardiography was 30 +/- 12 g; the mean difference was 1.9 +/- 2.3 g (p = not
      significant). Linear regression analysis between the 2 measurements was y = 0.97x
      - 1.12, r = 0.98. Dysfunctional mass derived from 3D echocardiography reflects
      the real site and extension of damaged myocardium.

PMID- 9662239
TI  - Three-dimensional echocardiographic reconstruction: description and applications
      of a simplified technique for quantitative assessment of left ventricular size
      and function.
AB  - A simplified system for three-dimensional (3D) reconstruction of the left
      ventricle and quantitation of its size and function is described. This system
      requires the acquisition of a minimum number of two-dimensional (2D)
      echocardiographic apical views, which are obtained by rotation of the probe about
      the initial imaging point. Traced endocardial borders are spatially reconstructed
      according to the common apex and longitudinal axis of the views and to the
      measured or assumed angular relation between scanned planes. This technique has
      been applied in vitro to regular and irregular ventricular phantoms, yielding
      excellent accuracy for volume calculation. Also, it has been applied clinically
      for left ventricular volume, stroke volume, and ejection fraction calculation in
      both normal subjects and patients with various cardiac diseases, providing good
      results compared with other independent imaging techniques and showing increased
      accuracy with respect to 2D echocardiographic methods. Because this is obtained
      without substantial increase in time, effort, or cost, this simplified technique
      for 3D reconstruction should therefore be of value in daily clinical
      echocardiographic practice.

PMID- 9662240
TI  - Role of stress echocardiography in heart failure.
AB  - Most patients presenting with heart failure have severe coronary artery disease.
      The identification of viable hibernating myocardium is of paramount clinical
      importance for a correct indication of revascularization. Contractile reserve may
      be identified when regional asynergy improves during low or moderate doses of
      dobutamine. Dipyridamole, given at infra-low dose, alone or preferably in
      association with a low dose of dobutamine, is another possible pharmacologic
      stress protocol. Dobutamine echocardiography has been found to be more specific
      than thallium scintigraphy for predicting functional recovery after
      revascularization. However, the absence of contractile reserve does not exclude
      the presence of myocardial viability: perfusion reserve may be too low because of
      a critical coronary artery stenosis, or profound ultrastructural changes of
      myocardial cells may be present, including significant loss of contractile
      material. Inotropic reserve can also be assessed by dobutamine stress
      echocardiography in patients with idiopathic cardiomyopathy. The evolution of
      hemodynamic variables can be measured during the stress test. Stress
      echocardiography, especially during exercise, could probably provide important
      information about heart failure associated with valvular heart disease.

PMID- 9662241
TI  - Diastolic heart failure: standard Doppler approach and beyond.
AB  - Evidence of normal systolic left ventricular function has been reported in up to
      30-40% of patients with clinical signs of congestive heart failure, suggesting
      that diastolic dysfunction is an important predictor of prognosis and mortality.
      Doppler echocardiography as a noninvasive diagnostic procedure is able to provide
      immediate and relevant information on functional and structural changes
      underlying the clinical syndrome of heart failure. Four distinct early
      filling/late diastole (E/A) ratio patterns (normal, delayed relaxation,
      pseudonormal, restrictive) can be discerned if viewed within the context of other
      available clinical information. These patterns evolve from one to another in a
      single individual, with changes in disease evolution, treatment, and loading
      condition. They represent a continuum from normal to severe diastolic
      dysfunction, showing progressively increasing left ventricular (LV) chamber
      stiffness and subsequently decreasing deceleration time. The combination of
      Doppler restrictive filling pattern and decreased deceleration time provides
      important information that helps to differentiate gradations of diastolic
      dysfunction and has been found to be a potent predictor of prognosis and
      mortality in various cardiac conditions. When clinical and transthoracic data
      alone are not sufficient in guiding therapy of congestive heart failure,
      transesophageal echocardiography can be used to assess most Doppler flows,
      especially pulmonary venous and left atrial (LA) appendage flows. The use of the
      multiplane transducer in multiple intermediate scan planes further improves the
      possibility of optimizing the Doppler incident angle and obtaining the best
      Doppler recordings of the left upper or right upper pulmonary venous flow.
      Whereas LV diastolic dysfunction is common in patients with congestive heart
      failure and appears to be an important predictor of prognosis, little information
      is available about right ventricular (RV) diastolic dysfunction. The role of RV
      function in congestive heart failure has probably been underestimated and it is
      possible that RV diastolic dysfunction assessment is equally important in the
      follow-up of heart failure patients. Recently, 2 novel echocardiographic
      technologies for the assessment of ventricular wall dynamics have been developed-
      color kinesis and tissue Doppler imaging. Both techniques have recently been
      shown to provide global as well as regional information on LV contraction and
      filling. Complementary use of both techniques may allow a more complete
      noninvasive assessment of global and regional systo-diastolic LV function.

PMID- 9662242
TI  - 123I-labelled vasoactive intestinal peptide receptor scintigraphy in patients
      with colorectal cancer.
AB  - Recent studies have shown that various gastrointestinal tumours express
      substantial amounts of vasoactive intestinal peptide (VIP) receptors. Based on
      these observations, we have developed a receptor scintigraphy using [123I]VIP as
      a radioligand. An initial series performed at our institution showed promising
      potential for visualization of various gastrointestinal adenocarcinomas by means
      of [123I]VIP. In this article, we now report the results obtained in 80
      consecutive patients with colorectal adenocarcinoma. Eighty consecutive patients
      with histologically verified colorectal cancer underwent scanning by means of
      [123I]VIP (1 microg, approximately 150 MBq). Thirteen patients were free of
      tumour after complete resection of Dukes' C cancer, eight patients presented with
      primary and 14 with locally recurrent tumours but were free of metastases. Ten
      patients had locally recurrent disease and liver, lung or lymph node metastases.
      Disease confined to organ metastases (i.e. liver, lung or lymph nodes) was
      present in 35 patients. The size of the primary or recurrent tumours ranged
      between 3 and 6 cm, and the size of metastases was between 1 and 13 cm in
      diameter. Scan results were evaluated independently by two nuclear medicine
      physicians in a blinded way, and results were then compared with computerized
      tomography (CT)scans not older than 4 weeks. Seven out of eight primary (87%) and
      21 out of 24 (82%) locally relapsing cancers were imaged with [123I]VIP. Negative
      VIP scans were obtained in all 13 patients in whom the cancers had been
      curatively resected. All patients with lymph node metastases showed positive VIP
      scans (four out of four), and positive scans were obtained in 25 out of 28 (89%)
      patients with liver metastases and in two out of three cases with lung
      metastases. In four patients with relapsing cancer, the VIP scan indicated the
      presence of disease before CT, and in two patients the diagnosis of scar tissue
      instead of a local recurrence of rectal cancer as suggested by CT could be
      established. We conclude that [123I]VIP receptor scanning is a sensitive method
      for radioimaging of colorectal cancer with the potential to provide valuable
      additional information to conventional radiological methods.

PMID- 9662243
TI  - A phase I study of the vitamin D analogue EB 1089 in patients with advanced
      breast and colorectal cancer.
AB  - Preclinical studies have shown that the vitamin D analogue EB 1089 has
      significantly less calcaemic activity than its parent compound 1,25
      dihydroxyvitamin D (1,25(OH)2D3) and significant anti-tumour activity. This phase
      I trial was designed to evaluate the calcaemic effect of the drug in patients
      with advanced cancer. EB 1089 was given to 36 patients with advanced breast and
      colorectal cancer in doses of between 0.15 and 17.0 microg m(-2) day(-1). Serial
      serum and urine calcium, urine creatinine and serum parathyroid hormone (PTH)
      were monitored. Hypercalcaemia was seen in all patients receiving 17.0 microg m(
      2) day(-1). Hypercalcaemia attributable to EB 1089 was reversible by
      discontinuing or reducing EB 1089 therapy. During the first 5 days of treatment,
      urine calcium (P = 0.0001) and serum-corrected calcium (P = 0.027) were related
      to EB 1089 dose, whereas serum parathyroid hormone (P = 0.0001) showed an inverse
      relationship. Twenty-one patients received compassionate treatment for between 10
      and 234 days. No complete or partial responses were seen. Six patients on
      treatment for more than 90 days showed stabilization of disease. EB 1089 was well
      tolerated and adverse events considered to be caused by EB 1089 were limited to
      dose-dependent effects on calcium metabolism. The dose estimated to be tolerable
      for most patients from this study is around 7 microg m(-2) day(1). These data
      support previous work that has demonstrated EB 1089 to be significantly less
      calcaemic than 1,25-dihydroxyvitamin D3.

PMID- 9662244
TI  - Microencapsulated octreotide pamoate in advanced gastrointestinal and pancreatic
      cancer: a phase I study.
AB  - Fourteen patients suffering from advanced colorectal (n = 7), pancreatic (n = 4)
      or gastric (n = 3) carcinomas received treatment with microencapsulated
      octreotide pamoate 90 mg i.m. every 4 weeks (n = 4), 160 mg i.m. every 4 weeks (n
      = 4) or 160 mg i.m. every 2 weeks (n = 6). Two patients had stable disease, one
      for 4 and one for 6 months. Plasma insulin-like growth factor (IGF)-I decreased
      by 49-53%, IGF-II by 27-37% and total IGF-binding protein (IGFBP)-3 by 16-19%,
      whereas IGFBP-1 increased by 35-55%. Insulin and C-peptide levels decreased by 29
      38% and 41-46% respectively. A non-significant decrease in urinary GH secretion
      and an increase in the ratio of fragmented to intact IGFBP-3 as well as IGFBP-3
      protease activity was seen. The increase in IGFBP-3 fragmentation correlated
      negatively with alterations in IGF-I and IGF-II (P < 0.05). We conclude that
      microencapsulated octreotide administered in doses up to 160 mg every 2 weeks is
      well tolerated and has pronounced effects on several components of the IGF system
      in plasma. In addition, changes in IGFBP-3 protease activity because of cancer
      may contribute to alterations in IGF-I and -II, indicating the importance of
      measuring this parameter in addition to IGFs and IGFBPs when evaluating
      alterations in IGF-I.

PMID- 9662245
TI  - Pulmonary function after treatment for acute lymphoblastic leukaemia in
      childhood.
AB  - The aim of this study was to examine pulmonary function after acute lymphoblastic
      leukaemia in childhood and identify risk factors for reduced pulmonary function.
      We studied a population-based cohort of 94 survivors of acute lymphoblastic
      leukaemia in childhood who were in first remission after treatment without spinal
      irradiation or bone marrow transplantation. Pulmonary function test results were
      compared with reference values for our laboratory, based on 348 healthy subjects
      who had never smoked from a local population study. A median of 8 years after
      cessation of therapy (range 1-18 years) the participants had a slight,
      subclinical, restrictive ventilatory insufficiency and reduced transfer factor
      and transfer coefficient. The changes in lung function were related to younger
      age at treatment and to more dose-intensive treatment protocols that specified
      more use of cranial irradiation and higher cumulative doses of anthracyclines,
      cytosine arabinoside and intravenous cyclophosphamide than previous protocols. We
      conclude that, 8 years after treatment without bone marrow transplantation or
      spinal irradiation, survivors of childhood acute lymphoblastic leukaemia in first
      remission were without pulmonary symptoms but had signs of slight restrictive
      pulmonary disease including reduced transfer factor. The increased dose intensity
      of many recent protocols for childhood acute lymphoblastic leukaemia may lead to
      increased late pulmonary toxicity.

PMID- 9662246
TI  - Clinical benefit from palliative chemotherapy in non-small-cell lung cancer
      extends to the elderly and those with poor prognostic factors.
AB  - The intention of this study was to identify the pretreatment characteristics
      predicting for the survival, objective response and symptom relief in patients
      with non-resectable, non-small-cell lung cancer (NSCLC) managed in the Lung Unit
      at the Royal Marsden Hospital. This analysis included 290 patients with advanced
      NSCLC generally treated with a cisplatin-based chemotherapy regimen in one of a
      series of trials. Thirty-seven pretreatment variables, response and survival data
      were collected prospectively and analysed using univariate and multivariate
      methods. By multivariate analysis performance status, disease extent and pattern
      of metastases along with certain biochemical features were influential
      independent variables for survival, objective and symptom response. Older age was
      positively associated with objective response (P = 0.04). When the independent
      factors for symptom response were used to group patients into prognostic
      categories, 30-48% of patients with an adverse set of factors had symptom relief.
      Similarly using the relative risk of death to subgroup the patient population,
      54% of patients at high risk of death (greater than 8.0), with a median survival
      of 2.5 months, had symptom relief. The data are consistent with other studies in
      identifying the pretreatment factors predicting for survival and objective
      response. Additionally, older age is positively associated with objective
      response and the majority of patients with the worst prognosis have symptom
      relief from treatment with chemotherapy.

PMID- 9662247
TI  - Phase II and pharmacokinetic study of paclitaxel therapy for unresectable
      hepatocellular carcinoma patients.
AB  - Hepatocellular carcinoma (HCC) is a common lethal disease in Asia and there is no
      effective chemotherapy. Identification of new effective drugs in the treatment of
      inoperable HCC is urgently need. This is a phase II clinical study to investigate
      the efficacy, toxicity and pharmacokinetics of paclitaxel in HCC patients. Twenty
      patients with measurable, unresectable HCC, normal serum bilirubin, normal bone
      marrow and renal functions were studied. Paclitaxel 175 mg m(-2) was given
      intravenously over 3 h every 3 weeks. No complete or partial responses were
      observed. Five patients had stable disease. Major treatment toxicities (grade 3
      4) were neutropenia (25%), thrombocytopenia (15%), infection (10%) and allergy
      (10%). Treatment-related deaths occurred in two patients. The median survival was
      12 weeks (range 1-36). Paclitaxel is metabolized by the liver and the
      pharmacokinetics of paclitaxel in cancer patients with liver involvement or
      impairment may be important clinically. Pharmacokinetic study was completed in 13
      HCC patients. The paclitaxel area under the curve was significantly increased (P
      < 0.02), clearance decreased (P < 0.02) and treatment-related deaths increased (P
      = 0.03) in patients with hepatic impairment. In conclusion, paclitaxel in this
      dose and schedule has no significant anti-cancer effect in HCC patients.
      Paclitaxel should be used with caution in cancer patients with liver impairment.

PMID- 9662248
TI  - Elevated pretreatment serum levels of soluble vascular cell adhesion molecule 1
      and lactate dehydrogenase as predictors of survival in cutaneous metastatic
      malignant melanoma.
AB  - Very rapid progression of disease with a median survival of 6-9 months is a
      common feature of metastatic cutaneous malignant melanoma. Nevertheless,
      substantial variability of survival suggests that metastatic cutaneous malignant
      melanoma can be divided into several biological subgroups. Pretreatment serum
      levels of soluble adhesion molecules and various clinical parameters in cutaneous
      metastatic malignant melanoma were evaluated to determine their prognostic value.
      In this study pretreatment serum levels of soluble vascular cell adhesion
      molecule 1 (sVCAM-1), soluble intercellular cell adhesion molecule 1 (sICAM-1),
      soluble endothelial leukocyte adhesion molecule 1 (sE-selectin) and multiple
      clinical factors were assessed in relation to overall survival of 97 consecutive
      patients with metastatic cutaneous malignant melanoma seen at our institution
      between May 1990 and April 1996. For statistical analysis, both univariate and
      multivariate Cox proportional-hazards models were used. Elevated pretreatment
      serum levels of sVCAM-1 (P < 0.005) and of lactate dehydrogenase (P < 0.002) were
      rendered statistically independent and were significantly associated with
      unfavourable outcome. Patients were assigned to one of three risk categories
      (low, intermediate and high) according to a cumulative risk score defined as the
      function of the sum of these two variables. There were significant differences in
      overall survival (P < 0.0001) between low- (n = 53, 5-year survival probability
      of 23.3%), intermediate- (n = 29, 5-year survival probability of 9.9%) and high
      risk (n = 15) patients. Elevated pretreatment serum levels of sVCAM-1 and of
      lactate dehydrogenase correlate with poor outcome in metastatic cutaneous
      malignant melanoma. These data support risk stratification for future therapeutic
      trials and identify factors that need to be validated in prospective studies and
      may potentially influence decision-making in palliative management of patients
      with disseminated cutaneous malignant melanoma.

PMID- 9662249
TI  - Is prostatic intraepithelial neoplasia in the transition/central zone a true
      precursor of cancer? A long-term retrospective study in Norway.
AB  - Prostatic intraepithelial neoplasia (PIN) has been considered as a precursor of
      prostatic cancer. Few reports have dealt with the long-term follow-up of PIN
      lesions, and there is still a lack of proof that PIN is a true premalignant
      lesion. The objective of this study was to evaluate PIN in the transition/central
      zone as a marker for subsequent development of prostatic cancer. The PIN status
      of tissue specimens from 789 men without prostate cancer was determined in 508
      transurethral resections and 281 transvesical prostatic enucleations. All slides
      were reviewed blind and independently by two pathologists. The patients were
      followed for an average of 11 years, and the incidence of subsequent cancer and
      cause-specific survival were analysed. Thirty-six cases of clinical prostatic
      cancer occurred among the cohort of 789 men through follow-up. No association
      between the presence of PIN in the transition/central zone and subsequent cancer
      development was found. There was also no difference in survival related to PIN
      status among the subsequent cancer patients.

PMID- 9662250
TI  - Cell cycle phase influences tumour cell sensitivity to aminolaevulinic acid
      induced photodynamic therapy in vitro.
AB  - Photodynamic therapy (PDT) is a form of cancer treatment based on the destruction
      of cells by the interaction of light, oxygen and a photosensitizer.
      Aminolaevulinic acid (ALA) is the prodrug of the photosensitizer protoporphyrin
      IX (PpIX). ALA-induced PDT depends on the rate of cellular synthesis of PpIX,
      which may vary with cell cycle phase. This study has investigated the
      relationship between cell cycle phase, PpIX generation and phototoxicity in
      synchronized and unsynchronized bladder cancer cells (HT1197). In unsynchronized
      cells, relative PpIX fluorescence values (arbitrary units) were significantly
      different between cell cycle phases after a 1-h ALA incubation (G1 24.8 +/- 0.7;
      S-phase, 32.7 +/- 0.8, P < 0.05; G2 35.4 +/- 0.8, P < 0.05). In synchronized
      cells after a 1-h ALA incubation, cells in G1 produced less PpIX than those in S
      phase or G2 [6.65 +/- 1.1 ng per 10(5) cells compared with 15.5 +/- 2.1 (P <
      0.05), and 8.1 +/- 1.8 ng per 10(5) cells (not significant) respectively] and
      were significantly less sensitive to ALA-induced PDT (% survival, G1 76.2 +/-
      8.3; S-phase 49.7 +/- 4.6, P < 0.05; G2 44.2 +/- 2.4, P < 0.05). This
      differential response in tumour cells may have implications for clinical PDT,
      resulting in treatment resistance and possible failure in complete tumour
      response.

PMID- 9662251
TI  - Localized hypothermia: impact on oxygenation, microregional perfusion, metabolic
      and bioenergetic status of subcutaneous rat tumours.
AB  - The effect of localized hypothermia on microcirculatory and metabolic parameters
      in s.c. DS sarcomas on the hind foot dorsum of Sprague-Dawley rats was
      investigated. Tumours were cooled by superfusion of the tumour surface with
      cooled saline solution to 25 degrees C or 15 degrees C. Control tumours remained
      at 35 degrees C. These temperatures were maintained for 30 min. In tumour
      oxygenation measurements, hypothermia at 25 degrees C and 15 degrees C caused
      progressive decreases in the size of the fraction of pO2 measurements between 0
      and 2.5 mmHg together with a reduction in pO2 variability. No significant changes
      in median or mean pO2 or in the fraction of pO2 measurements between 0 and 5
      mmHg, and 0 and 10 mmHg were observed. Using laser Doppler flowmetry, red blood
      cell flux was found to decrease significantly upon 25 degrees C or 15 degrees C
      hypothermia treatment to 67% and 37% of starting values respectively, whereas no
      significant changes were seen in control tumours over the whole observation
      period. Viscosity was measured in blood and plasma samples over a range of
      temperatures and was found to increase with decreasing temperature. Assessment of
      tumour glucose levels showed an increased concentration of glucose following 15
      degrees C hypothermia, an observation consistent with a 'slowing down' of
      glycolysis. No changes in lactate or adenylate phosphate levels were observed. As
      a way of improving tumour oxygenation, localized hypothermia may therefore be a
      useful means of radiosensitization.

PMID- 9662252
TI  - Thymidylate synthase expression and activity: relation to S-phase parameters and
      5-fluorouracil sensitivity.
AB  - Six human cancer cell lines exhibiting a large range of sensitivity to 5
      fluorouracil (5-FU) were evaluated for thymidylate synthase (TS) and p53 gene
      expression, TS and dihydropyrimidine dehydrogenase (DPD) activity, as well as
      cell cycle parameters, S-phase fraction (SPF), bromodeoxyuridine labelling index
      (LI) and S-phase duration (SPD). All these parameters were investigated for 7
      days in asynchronously growing cell populations and compared with the cell
      sensitivity to 5-FU. No significant correlation was found between S-phase
      parameters and TS gene expression and/or activity. TS activity was higher in
      proliferating cells; however, it was not significantly higher in rapidly growing
      cell lines with short SPD. Neither TS gene expression nor activity was found to
      correlate with 5-FU sensitivity. On the another hand, a statistically significant
      correlation (P < 0.0001) was observed between LI and SPD and 5-FU sensitivity.
      The present results suggest that cell cycle parameters such as SPD and/or LI
      could be better parameters for 5-FU sensitivity prediction than TS gene
      expression and/or activity. This could be especially informative in cases of
      concomitant radio-chemotherapy as S-phase parameters are already proposed for
      hyperfractionated radiotherapy planning.

PMID- 9662253
TI  - Mutations in the TP53 gene and protein expression of p53, MDM 2 and p21/WAF-1 in
      primary cervical carcinomas with no or low human papillomavirus load.
AB  - Several studies have focused on the role of p53 inactivation in cervical cancer,
      either by inactivating mutations in the TP53 gene or by degradation of the p53
      protein by human papillomavirus (HPV). In this study, primary cervical carcinomas
      from 365 patients were analysed for presence of HPV using both consensus primer
      sets and type-specific primer-sets. Nineteen samples were determined to have no
      or low virus load, and were selected for further analyses: mutation screening of
      the TP53 gene using constant denaturant gel electrophoresis (CDGE) followed by
      sequencing, and protein expression of p53, MDM2 and p21 using
      immunohistochemistry (IHC). Mutations in the TP53 gene were found in eight
      samples (42%). Elevated p53 protein expression was significantly associated with
      presence of a mutation (P < 0.007). P21 protein expression was detected in 16 of
      the 19 carcinomas. No p21 expression was seen in normal cervical tissue. Two
      samples, both with wild-type p53, had elevated MDM2 expression. Compared with a
      previous study from our group, of mainly HPV-positive cervical carcinomas, in
      which only one sample was found to contain a TP53 mutation, a significantly
      higher mutation frequency (P < 0.001) was found among the carcinomas with no or
      low virus load. Although p53 inactivation pathways are not detected in every
      tumour, our study supports the hypothesis that p53 inactivation, either by
      binding to cellular or viral proteins or by mutation, is essential in the
      development of cervical carcinomas.

PMID- 9662254
TI  - Genetic analysis of lung tumours of non-smoking subjects: p53 gene mutations are
      constantly associated with loss of heterozygosity at the FHIT locus.
AB  - Lung cancer is strictly associated with tobacco smoking. Tumours developed in non
      smoking subjects account for less than 10% of all lung cancers and show peculiar
      histopathological features, being prevalently adenocarcinomas. A number of
      genetic data suggest that their biological behaviour may be different from that
      of lung tumours caused by smoking, however the number of cases investigated to
      date is too low to draw definitive conclusions. We have examined the status of
      p53 and K-ras genes and the presence of loss of heterozygosity (LOH) at the FHIT
      locus in a series of 35 lung adenocarcinomas that developed in subjects who had
      never smoked. Results were compared with those obtained in a series of 35 lung
      adenocarcinomas from heavy-smoking subjects. In the group of non-smoking subjects
      p53 mutations and LOH at the FHIT locus were present in seven (20%) cases, and
      the two alterations were constantly associated (P < 0.0001), whereas they were
      not related in the series of carcinomas caused by smoking. In tumours developed
      in heavy-smoking subjects, the frequency of LOH at the FHIT locus was
      significantly higher (P = 0.006) than in tumours from non-smoking subjects. The
      frequency of p53 mutations in adenocarcinomas caused by smoking was not different
      from that seen in non-smoking subjects. However, in the group of smoking subjects
      we observed mostly G:C --> T:A transversions, whereas frameshift mutations and
      G:C --> A:T transitions were more frequently found in tumours from non-smoking
      subjects. No point mutations of the K-ras gene at codon 12 were seen in subjects
      who had never smoked, whereas they were present (mostly G:C --> T:A
      transversions) in 34% of tumours caused by smoking (P = 0.002). Our data suggest
      that lung adenocarcinomas developed in subjects who had never smoked represent a
      distinct biological entity involving a co-alteration of the p53 gene and the FHIT
      locus in 20% of cases.

PMID- 9662255
TI  - Effects of retinoic acid and fenretinide on the c-erbB-2 expression, growth and
      cisplatin sensitivity of breast cancer cells.
AB  - We investigated the effects of all-trans retinoic acid (ATRA) and fenretinide (4
      HPR) on c-erbB-2 expression in SK-BR-3, BT-474 and MCF-7 breast cancer cells and
      on the growth, differentiation, apoptosis and cisplatin (CDDP) sensitivity of SK
      BR-3 cells. It has been reported that oestrogen inhibits c-erbB-2 in oestrogen
      receptor-positive breast cancer cells. Using ELISA, Western and Northern analysis
      we have demonstrated that ATRA and 4-HPR exert similar effects down-regulating c
      erbB-2 protein and mRNA in c-erbB-2-overexpressing SK-BR-3 and BT-474 and in
      normally expressing MCF-7 cells. Both retinoids inhibit SK-BR-3 cell growth. ATRA
      induces cellular enlargement and flattening, suggesting epithelial
      differentiation. 4-HPR causes nuclear and cytoplasmic condensation, DNA
      fragmentation and externalization of phosphatidylserine, indicating apoptosis. c
      erbB-2 expression/activity has been linked to sensitivity against CDDP.
      Therefore, combinations of ATRA or 4-HPR with CDDP were tested for their anti
      proliferative activity. Retinoid-conditioned cells were either exposed to
      retinoid and CDDP (schedule I, 'continuous retinoid treatment') or to CDDP alone
      (schedule II, 'retinoid pretreatment'). This retinoid-conditioning followed by
      CDDP +/- retinoid yields stronger growth inhibition compared with unconditioned
      cells, which were exposed to CDDP +/- retinoid (schedule III, 'no retinoid
      pretreatment'). The inefficacy of schedule III indicates that retinoid
      conditioning is essential for the improvement of the antiproliferative effect.
      The interactions in schedules I and II are synergistic for ATRA and CDDP, but
      slightly antagonistic for 4-HPR and CDDR However, 4-HPR + CDDP is more effective
      in growth inhibition than each drug alone.

PMID- 9662256
TI  - Oestradiol regulation of the components of the plasminogen-plasmin system in MDA
      MB-231 human breast cancer cells stably expressing the oestrogen receptor.
AB  - To understand the hormonal regulation of the components of the plasminogen
      plasmin system in human breast cancer, we examined the oestradiol (E2) regulation
      of plasminogen activators (PAs), namely urokinase-type plasminogen activator
      (uPA) and tissue-type plasminogen activator (tPA), plasminogen activator
      inhibitor type 1 (PAI-1) and uPA receptor (uPAR), in our model system. We used
      stable transfectants of the MDA-MB-231 human breast cancer cells that express
      either the wild-type (S30 cells) or the mutant 351asp-->tyr oestrogen receptor
      (ER) (BC-2 cells). Northern blot analysis showed that there was a concentration
      dependent down-regulation of uPA, tPA and PAI-1 mRNAs by E2. In contrast, uPAR
      mRNA was not modulated by E2. The pure anti-oestrogen ICI 182,780 was able to
      block E2 action, indicating that the regulation of these genes is ER mediated.
      The E2 also inhibited the expression and secretion of uPA, tPA and PAI-1 proteins
      as determined by enzyme-linked immunosorbent assay (ELISA) in cell extracts (CEs)
      and conditioned media (CM). Zymography of the CM confirmed the inhibitory effect
      of E2 on uPA activity. Thus, we now report the regulation of uPA, PAI-1 and tPA
      by E2 in both mRNA and protein levels in ER transfectants. The association
      between down-regulation of the uPA by E2 and known E2-mediated growth inhibition
      of these cells was also explored. Our findings indicate that down-regulation of
      uPA by E2 is an upstream event of inhibitory effects of E2 on growth of these
      cells as the addition of exogenous uPA did not block the growth inhibition by E2.

PMID- 9662257
TI  - Enzyme-linked immunosorbent assay of epidermal growth factor receptor in lung
      cancer: comparisons with immunohistochemistry, clinicopathological features and
      prognosis.
AB  - The prognostic role of epidermal growth factor receptor (EGFR) remains
      controversial in patients with lung cancer. Previous assays for EGFR have
      primarily been qualitative or, at best, semiquantitative. In the present study,
      using fresh-frozen tissue from 190 unselected lung cancer patients,
      quantification of EGFR (EGFR(ELISA)) using a recently developed enzyme-linked
      immunosorbent assay (ELISA) technique was compared with results (EGFR(IHC))
      obtained using immunohistochemistry (IHC). Correlation between results obtained
      by the two different techniques was highly significant (r(s) = 0.63, P < 0.001, n
      = 190). This correlation improved even further (r(s) = 0.76) when sections were
      estimated using an IHC score that took into account percentage staining,
      intensity and relative tumour area. Furthermore, the relationship between
      clinicopathological features and prognosis was identical for the two methods. The
      expression of EGFR was highest in squamous cell carcinomas, but it was not
      correlated with other characteristics such as age, sex, histological grading,
      stage or prognosis. We conclude that evaluation of EGFR content using IHC and
      ELISA produces comparable results.

PMID- 9662258
TI  - Bax expression has prognostic significance that is enhanced when combined with
      AgNOR counts in glottic carcinomas.
AB  - Using nucleolar organizer regions (NORs) as a proliferative marker and Bax
      expression as a marker for apoptosis, we have studied the individual and combined
      prognostic significance of these markers. Successive sections of diagnostic,
      formalin-fixed and paraffin-embedded specimens from 69 patients with T1-4 tumours
      were stained with a rabbit anti-human Bax polyclonal antibody and silver nitrate
      for visualization of NORs (AgNORs). After classification for staining intensity
      and the percentage of Bax expression, a final score resulting in four classes of
      increasing Bax expression was obtained. AgNOR counts were expressed as mean
      counts (mAgNOR) and the percentage of tumour nuclei with more than one AgNOR
      (pAgNOR>1). Both AgNOR parameters were grouped in three classes with increasing
      values. Low Bax scores correlated significantly with poor prognosis (P = 0.0106).
      For mAgNOR and pAgNOR>1, high values correlated with poor prognosis (P = 0.0185
      and P = 0.0003 respectively). A combined parameter, for which the Bax score was
      subtracted from the AgNOR scores, appeared to be statistically stronger than the
      individual parameters (P < 0.0001). Both Bax expression and AgNOR scores, and in
      particular the combination of these parameters, appear to be strong prognostic
      markers in glottic squamous cell carcinomas.

PMID- 9662259
TI  - Serum polysialylated neural cell adhesion molecule in childhood neuroblastoma.
AB  - Neuroblastoma cells express the polysialylated form of the neural cell adhesion
      molecule (NCAM), which normally becomes restricted to a few neural tissues after
      embryogenesis. In this study, we investigated serum levels of polysialylated NCAM
      in 14 children with different grades and stages of neuroblastoma using an
      immunoluminescence assay, and compared the results to 269 healthy control
      subjects. Simultaneously, the polysialylated NCAM content of the tumours was
      determined by immunohistochemistry. Serum levels were dramatically elevated (more
      than sixfold) in children with advanced stages and fatal courses of disease,
      whereas children with differentiated tumour types and limited disease had low or
      normal levels. Serum concentrations correlated with the polysialylated NCAM
      content of the tumours, and they decreased during successful therapy. We
      therefore suggest polysialylated NCAM to be a useful marker monitoring childhood
      neuroblastoma.

PMID- 9662260
TI  - The suppression of fibroblast growth factor 2/fibroblast growth factor 4
      dependent tumour angiogenesis and growth by the anti-growth factor activity of
      dextran derivative (CMDB7).
AB  - Our previous studies showed that carboxymethyl benzylamide dextran (CMDB7) blocks
      basic fibroblast growth factor (FGF-2)-dependent cell proliferation of a human
      breast epithelial line (HBL100), suggesting its potential role as a potent
      antiangiogenic substance. The derived cell line (HH9), which was transformed with
      the hst/FGF4 gene, has been shown to be highly proliferative in vitro and to
      induce angiogenic tumours in nude mice. We show here that CMDB7 inhibits the
      mitogenic activities of the conditioned media from HBL 100 and HH9 cells in a
      dose-dependent manner. When HH9 cells were injected s.c. into nude mice, CMDB7
      treatment (300 mg kg(-1) week(-1)) suppressed the tumour take and the tumour
      growth by about 50% and 80% respectively. Immunohistochemical analysis showed a
      highly significant decrease, by more than threefold, in the endothelial density
      of viable tumour regions, together with a significant increase in the necrosis
      area. This antiangiogenic activity of CMDB7 was further demonstrated by direct
      inhibition of calf pulmonary artery (CPAE) and human umbilical vein (HUVEC)
      endothelial cell proliferation and migration in vitro. In addition, we showed
      that CMDB7 inhibits specifically the mitogenic effects of the growth factors that
      bind to heparin such as FGF-2, FGF-4, platelet-derived growth factor (PDGF-BB)
      and transforming growth factor (TGF-beta1), but not those of epidermal growth
      factor (EGF) and insulin-like growth factor (IGF-1). These results demonstrate
      that CMDB7 inhibits FGF-2/FGF-4-dependent tumour growth and angiogenesis, most
      likely by disrupting the autocrine and paracrine effects of growth factors
      released from the tumour cells.

PMID- 9662261
TI  - Seasonal variations in the onset of childhood leukaemia and lymphoma.
AB  - Infection has long been suspected as a possible factor in the aetiology of
      leukaemia and lymphoma. If seasonal variation in the onset of disease could be
      shown in any of the diagnostic subgroups of leukaemia or lymphoma, this would
      provide supportive evidence of an aetiology linked to exposure to infection. All
      cases in the Manchester Children's Tumour Registry (aged 0-14 years at diagnosis)
      with acute lymphoblastic leukaemia (ALL), acute non-lymphocytic leukaemia (ANLL),
      Hodgkin's disease (HD) or non-Hodgkin lymphoma (NHL) between 1 January 1954 and
      31 December 1996 were included in an analysis of seasonal variation in the month
      of first symptom and the month of diagnosis. Cases of common acute lymphoblastic
      leukaemia (c-ALL) diagnosed from 1979 onwards were also analysed separately. The
      groups considered for analysis were: all cases of ALL (n = 1070), ALL diagnosed
      between 18 and 95 months of age (n = 730), ALL diagnosed over 95 months of age (n
      = 266), c-ALL (n = 309), ANLL (n = 244), all infant acute leukaemias (ALL and
      ANLL under 18 months; n = 107), HD (n = 166) and NHL (n = 189). Using the Edwards
      method, both c-ALL and HD demonstrated significant seasonal variation (P = 0.037
      and 0.001 respectively) in date of first symptom, with peaks occurring in
      November and December respectively. Using this method, no indication of seasonal
      variation was found in the other diagnostic groups for date of first symptom or
      in any of the diagnostic groups for date of diagnosis. For comparison with a
      previous study, a further analysis based on date of diagnosis for all ALL cases,
      using summer-winter ratios, showed a significant summer excess. These results
      provide supportive evidence for an infectious aetiology for c-ALL and HD, and
      possibly for all ALL, which warrants further investigation.

PMID- 9662262
TI  - Gastric cancer risk in relation to Helicobacter pylori infection and subtypes of
      intestinal metaplasia.
AB  - Helicobacter pylori (H. pylori) infection and intestinal metaplasia (IM) are each
      associated with an increased risk of gastric cancer (GC). To explore further the
      influences of H. pylori and IM on GC, H. pylori and subtypes of IM were evaluated
      in 135 sex and age-matched case and control pairs. Odds ratios (ORs) with 95%
      confidence intervals of developing GC were calculated for each risk factor using
      multiple logistic regression analysis. ORs for H. pylori infection and IM were
      2.43 (1.29-4.65) and 4.59 (2.58-8.16), respectively, and those for different IM
      subtypes gave values of 0.82 (0.28-2.36) for type I, 2.03 (0.95-4.34) for type II
      and 39.75 (14.34-110.2) for type III. Stratification analysis by histological
      subtype and stage of GC showed a particularly high OR for IM in intestinal type
      (12.8, 4.73-34.83) and early GC (6.40, 2.25-18.18). Our data indicate that both
      H. pylori and IM are related to GC risk. Type III IM is a more specific marker of
      premalignancy, with relevance, in particular, to the early and intestinal type of
      GC.

PMID- 9662263
TI  - Intake of nitrate and nitrite and the risk of gastric cancer: a prospective
      cohort study.
AB  - The association between the intake of nitrate or nitrite and gastric cancer risk
      was investigated in a prospective cohort study started in 1986 in the
      Netherlands, of 120,852 men and women aged 55-69 years. At baseline, data on
      dietary intake, smoking habits and other covariates were collected by means of a
      self-administered questionnaire. For data analysis, a case-cohort approach was
      used, in which the person-years at risk were estimated from a randomly selected
      subcohort (1688 men and 1812 women). After 6.3 years of follow-up, 282
      microscopically confirmed incident cases of stomach cancer were detected: 219 men
      and 63 women. We did not find a higher risk of gastric cancer among people with a
      higher nitrate intake from food [rate ratio (RR) highest/lowest quintile = 0.80,
      95% CI 0.47-1.37, trend-P = 0.18], a higher nitrate intake from drinking water
      (RR highest/lowest quintile = 0.88, 95% CI 0.59-1.32, trend-P = 0.39) or a higher
      intake of nitrite (RR highest/lowest quintile = 1.44, 95% CI 0.95-2.18, trend-P =
      0.24). Rate ratios for gastric cancer were also computed for each tertile of
      nitrate intake from foods within tertiles of vitamin C intake and intake of beta
      carotene, but no consistent pattern was found. Therefore, our study does not
      support a positive association between the intake of nitrate or nitrite and
      gastric cancer risk.

PMID- 9662264
TI  - Smoking and risk of colorectal cancer.
AB  - Tobacco smoking was studied in relation to colorectal cancer in 56 973 Finnish
      men and women initially free from cancer. Smoking status was determined by a
      health questionnaire. During a follow-up period of 28 years, from the baseline in
      1966-72 to the end of 1994, 457 cases of colorectal cancer occurred. There was no
      significant association between baseline smoking status and colorectal cancer
      risk over the total follow-up period. The sex- and age-adjusted relative risk of
      colorectal cancer between smokers and non-smokers was 1.06 (95% confidence
      interval 0.84-1.33). For follow-up periods of 11-20 years, however, the relative
      risk was 1.57 (95% confidence interval 1.09-2.24). In a subgroup in which smoking
      habits were assessed twice, the relative risk of colorectal cancer among
      persistent smokers was 1.71 (95% confidence interval 1.09-2.68) compared with
      others. The results of the present prospective study are consistent with the
      possibility that smoking increases the risk of colorectal cancer after a
      relatively long induction period. To clarify the role of smoking in colorectal
      cancer development, further cohort studies are needed with long follow-up periods
      and allowing for control of dietary and other potential confounding factors.

PMID- 9662265
TI  - Non-cryopreserved peripheral blood stem cells autotransplants for hematological
      malignancies can be performed entirely on an outpatient basis.
AB  - We have prospectively performed peripheral blood stem cell autotransplants in six
      patients with hematological malignancies on an entirely outpatient basis.
      Patients were conditioned with high-dose melphalan and received a median of 4.2 x
      10(8)/kg non-cryopreserved, non-purged mononuclear cells, containing a median of
      3.9 x 10(6)/kg CD34 + cells. The median time to achieve > 500 granulocytes/microl
      was 21 days, with a range of 16 to 40, whereas the median time to achieve >
      20,000 platelets/microl was 38 days, with a range of 21 to 48. Only three
      patients were transfused with platelets whereas packed red blood cells were
      transfused in two. All patients survived 60 days after the autograft and three
      are alive at 450, 690, and 1,950 days after the autotransplant. One patient was
      given an allogeneic bone marrow transplant when relapsing after the
      autotransplant. One patient had to be admitted to the hospital on day +10 because
      of fever. A median of 6,500.00 USD per patient was calculated as the total cost
      of each outpatient autotransplant. Since outpatient autologous transplants with
      non-frozen PBSC are feasible, restrictions to PBSC autotransplant programs may be
      overcome and costs may be diminished.

PMID- 9662266
TI  - Intravascular and total body platelet equilibrium in healthy volunteers and in
      thrombocytopenic patients transfused with single donor platelets.
AB  - Instrument platelet counts used in corrected count increment (CCI) and percent
      platelet recovery (PPR) formulas presume the transfused platelets are in
      equilibrium during the first hour after platelet transfusion. The timing of the
      pre-transfusion count affects CCI results, and we postulate that timing of CCI
      post transfusion affects CCI results. Platelet equilibrium using indium-111
      platelet transfusions has not been reported. Platelet redistribution was studied
      in 16 healthy volunteers and 12 thrombocytopenic patients by generally infusing
      less than 72-hr stored single-donor platelets along with an aliquot of indium-111
      labeled platelets by intravenous push. Counts were measured at 10, 15, 20, 60,
      and 120 min, and 24, 48, 72 hr along with continuous body scanning for 2 hr in
      healthy volunteers, and static organ scanning in patients and volunteers. Results
      indicated transfused platelets do not reach intravascular equilibrium for 60 min
      post-infusion and that the 10-min count cannot detect platelet refractoriness.
      However, total body equilibrium varies considerably between normal volunteers and
      thrombocytopenic patients. It is recommended to continue with the 1-hr post
      transfusion count.

PMID- 9662267
TI  - Phase changes in membrane lipids in sickle red cell shed-vesicles and sickle red
      cells.
AB  - Lipid phase transformations may occur in the membranes of sickle red cell shed
      vesicles and sickle red cells. The presence of such phase changes could be
      important in sickle cell disease since membrane phase changes appear to
      contribute to the generation of antiphospholipid antibodies that are
      thrombophilic and occur in sickle cell disease. In the present study, we have
      evaluated sickle red cell shed-vesicles and sickle red cells for the presence of
      non-bilayer lipid phases using 31P-NMR spectroscopy. Results show that the
      spectra of both the shed-vesicles and the sickle red cells are compatible with
      the occurrence of non-bilayer phases in the membrane bilayers. The findings
      support the concept that these membranes could contribute to the generation of
      antiphospholipid antibodies in sickle cell disease.

PMID- 9662268
TI  - IL-12 indirectly enhances proliferation of 5-FU-treated human hematopoietic
      peripheral blood CD34+ cells.
AB  - Interleukin-12 (IL-12) or natural killer cell stimulatory factor (NKSF), has
      multiple effects on T lymphocytes and natural killer cells. In this study, the
      effect of IL-12 on human hematopoiesis was studied by analyzing the growth of
      CD34+ peripheral blood stem cells (PBSC), in steady state. In the presence of
      Epo, IL-12 alone or in combination with IL-3 or SCF had no effect on the
      formation of colonies from CD34+ cells. In culture with Epo, G-CSF, and IL-3, the
      effect of Flt3-ligand (FL) on CD34+ PBSC was investigated in the presence or
      absence of IL-12. No additional effect of IL-12 was observed when combined with
      FL. We evaluated 5-FU-treated human CD34+ PBSC proliferation in cultures with
      Epo, G-CSF, and IL-3, in the presence or absence of IL-12. No cytokine
      combination enhanced colony formation from 5-FU-treated CD34+ cells. However, in
      cultures of 5-FU-treated human CD34+ cells, the most efficient combination was IL
      3 + Epo + G-CSF + Accessory cells (CD34-). Furthermore, IL-12 enhanced this
      colony formation significantly. To investigate whether immature CD34+ cells were
      responsible for FL or SCF, 5-FU-treated human CD34+ cells were cultured with or
      without IL-12. Whereas no synergistic effect was observed in combination with IL
      12, SCF alone significantly enhanced colony formation. However, the colony number
      was found to be smaller than with the potent combination of accessory cells in
      the presence of IL-12. These results indicate that accessory cells, lost in CD34+
      cell purification, could be partly responsible for an IL-12 effect on immature
      human PBSC proliferation.

PMID- 9662269
TI  - Poor outcome in disseminated intravascular coagulation or thrombotic
      thrombocytopenic purpura patients with severe vascular endothelial cell injuries.
AB  - Various hemostatic and vascular endothelial cell markers were measured in
      patients with disseminated intravascular coagulation (DIC), non-DIC, or
      thrombotic thrombocytopenic purpura (TTP) and in healthy volunteers to examine
      the relationships between the hemostatic abnormalities or vascular endothelial
      cell injuries and the patients' outcomes. Although the plasma levels of soluble
      fibrin monomer, thrombin-antithrombin complex, plasmin-plasmin inhibitor complex,
      and D-dimer were significantly increased in the DIC patients, there were no
      significant differences in these markers between the DIC patients who survived
      and those who died, suggesting that these markers might not be directly related
      to the patient outcome. The plasma thrombomodulin (TM) levels in the DIC and TTP
      patients were significantly higher than those in the healthy volunteers, and the
      plasma TM levels in the patients who died were significantly higher than those in
      the patients who survived. These findings showed that the TM level reflected the
      outcome, and that the outcome of the diseases underlying DIC and TTP might depend
      on vascular endothelial cell injuries. The plasma protein C and antithrombin
      activities were markedly reduced in the DIC, non-DIC, and TTP patients who died
      compared to those who survived. These findings suggest that reduced plasma
      antithrombin and protein C activities are useful markers of systemic vascular
      endothelial injuries. Although the plasma tissue factor (TF) levels were
      significantly increased in the DIC patients, there was no significant difference
      in the plasma TF levels between the DIC patients who died and those who survived.
      In conclusion, we found that the outcome of the diseases underlying DIC and TTP
      is related to vascular endothelial cells, and that plasma TM, antithrombin, and
      protein C are useful markers for systemic vascular endothelial cell injury.

PMID- 9662270
TI  - Elevated plasma endothelin-1 levels in sickle cell anemia: relationships to
      oxygen saturation and left ventricular hypertrophy.
AB  - Endothelin-1 (Et-1) is a vasoconstrictor produced by endothelial and vascular
      smooth muscle cells in response to hypoxia, which induces hypertrophy in cultured
      cardiac myocytes. We measured plasma Et-1 levels and left ventricular dimensions
      in 13 patients with sickle cell anemia (SCD) and in 12 African-American controls
      ages 16-29 years. Endothelin-1 concentrations are significantly higher in SCD
      subjects than controls (10.6 +/- 1.9 vs. 3.0 +/- 1.3 pmol/L). There was a
      negative correlation between oxygen saturation and Et-1 levels in SCD patients (r
      = -0.71, P = 0.01). SCD subjects have more dilated and hypertrophied hearts
      corrected for body surface area than controls as evidenced by significant
      increases in left ventricular end diastolic dimension (31 +/- 0.8 vs. 24 +/- 0.9
      mm/m2, P < 0.001), left ventricular end systolic dimension (20 +/- 0.9 vs. 16 +/-
      0.8 mm/m2, P = 0.002), left ventricular posterior wall thickness (5.0 +/- 0.1 vs.
      4.0 +/- 0.1 mm/m2, P < 0.001), and left ventricular mass (125 +/- 7.2 vs. 69 +/-
      5.1 g/m2, P < 0.001). The index of left ventricular function, the shortening
      fraction, was not different between groups (34 +/- 1.2% in SCD vs. 35 +/- 1.5% in
      controls). The correlation between left ventricular mass and levels of Et-1 in
      SCD subjects was not significant (r = 0.47, P = 0.121).

PMID- 9662271
TI  - Preliminary characterization of a structural defect in homozygous sickled cell
      alpha spectrin demonstrated by a rabbit autoantibody.
AB  - We have identified a rabbit autoantibody that strongly reacts with the core
      membrane skeleton of control red blood cells, and does not react with low- or
      high-density sickle cell core skeletons upon indirect immunofluorescence. Western
      blot analysis of red blood cell membrane proteins, utilizing this autoantibody,
      indicated no reactivity to any protein when SDS-PAGE was conducted in the
      presence of the reducing agent, dithiothreitol. However when SDS-PAGE was
      performed on control red blood cell membrane proteins separated in the absence of
      dithiothreitol, the autoantibody specifically reacted with a high molecular
      weight polypeptide (apparent Mr approximately equal to 310 kD) representing a DTT
      sensitive form of control alpha spectrin, which we refer to as alpha' spectrin.
      There was no staining of high density or low density sickle cell alpha or alpha'
      spectrin. This autoantibody should be an excellent tool for the fine mapping of
      structural change(s) in control vs. sickle cell alpha spectrin, and determination
      of whether the structural alteration effects spectrin dimer-tetramer
      interconversion and/or the spectrin-actin interaction. The modification in alpha
      spectrin, detected by this antibody, is very specific for homozygous SS alpha
      spectrin because sickle cell beta+ thalassemic alpha spectrin and sickle cell
      trait alpha spectrin react intensely with the autoantibody.

PMID- 9662272
TI  - Cryohemolysis for the detection of hereditary spherocytosis: correlation studies
      with osmotic fragility and autohemolysis.
AB  - Laboratory methods aimed to assess the presence of spheroidal cells such as
      osmotic fragility, autohemolysis, and glycerol lysis time are very elaborate,
      time consuming, and often give inconclusive results. We have developed a
      diagnostic test based on a unique sensitivity of HS cells to hypertonic
      cryohemolysis and analyzed blood samples of 55 HS patients. The patients were
      divided into two subgroups, clinically affected probands and their relatives. To
      get quantitative comparisons with the classic methods, the cryohemolysis results
      were compared to two parameters of the osmotic fragility test: the salt
      concentration that causes 50% hemolysis, and the percent lysis at a constant salt
      concentration. Autohemolysis results were also compared. To evaluate which of
      these tests has the best analytical power, we calculated the mean results and 2
      SDs of each parameter in a control group, and then looked to see which of them
      was best in identifying the patients. The cryohemolysis test was the single
      parameter that identified all cases including asymptomatic carriers of the
      disease. The ability of this test to identify the less severe cases probably
      reflects the dependency of the cryohemolysis on factors that are more related to
      the primary membrane molecular defects and less by the surface area to volume
      ratio.

PMID- 9662273
TI  - Mutation analysis of the HFE gene associated with hereditary hemochromatosis in
      African Americans.
AB  - Homozygosity for the mutation Cys282Tyr in the HFE gene has recently been
      identified as a cause of hereditary hemochromatosis, a disorder resulting in the
      inappropriate absorption of iron. Approximately 10% of Caucasians are
      heterozygous for this mutation; however, the gene frequency in African Americans
      is unknown. A study of a control population of African Americans was performed to
      determine the frequency of the Cys282Tyr and His63Asp alleles in this ethnic
      group. The carrier frequency for each mutant allele in our African American
      population was 3.0%. DNA studies of four African-American hemochromatosis
      patients did not identify any individuals with the Cys282Tyr allele. These
      findings suggest that if the Cys282Tyr mutation confers susceptibility to
      hemochromatosis in Caucasians (as suggested by recent studies) there is an
      alternative mechanism for hemochromatosis in the American black population.

PMID- 9662274
TI  - Interferon-gamma (IFN-gamma) as a potential radio- and chemo-protectant.
AB  - Interferons (IFN) have had increasing clinical usage in the treatment of a
      variety of disorders, at times being used in combination with chemo- or
      radiotherapy. However, interferons may have inhibitory effects on hematopoietic
      stem cell proliferation and the effects of this cytokine's use on long-term
      hematologic function have not been studied. We performed the competitive
      repopulation assay in the murine system, using cells exposed to irradiation or
      single-dose chemotherapy with or without concomitant IFN-gamma use. IFN-gamma
      alone had no deleterious effects on hematopoietic stem cell productivity. We
      measured the repopulating ability of exhaustible multilineage precursors that
      were present at early stages of marrow repopulation after competitive
      repopulation (30 days). These progenitors were minimally impacted by
      cyclophosphamide (CTX) with or without IFN-gamma. Irradiation (XRT) and CTX alone
      produced significant repopulating defects in the most primitive hematopoietic
      stem cell, PHSC. Addition of IFN to either treatment regimen resulted in
      protection of PHSC, with improved repopulating ability, although the levels of
      donor marrow reached control levels only when CTX and IFN were used together. The
      results of multiple use of IFN with chemotherapy must be studied further, but IFN
      may offer hematologic radio- and chemoprotection, in addition to its antitumor
      properties in clinical protocols for treatment of cancers.

PMID- 9662275
TI  - Increased tyrosine phosphorylation of band 3 in hemoglobinopathies.
AB  - In order to investigate the tyrosine phosphorylation of band 3, we performed
      immunoblotting of intact red cells using anti-phosphotyrosine antibody of 21
      patients with sickle cell disorders (11 SS, 5 Sbeta, 5 SC), 7 patients with beta
      thalassemias (5 beta thal intermedia, 2 deltabeta thal), 10 normal controls, and
      1 patient with hereditary spherocytosis. They had not received transfusion for
      the last 4 months and all were clinically stable. Our results showed an increased
      tyrosine phosphorylation of two proteins, in the 100 and 80 kD regions, in sickle
      cell and beta-thalassemic red cells when compared to the normal controls and to
      the patient with hereditary spherocytosis. Immunoprecipitation of the lysed red
      cells with anti-band 3 antibody and immunoblotting with anti-phosphotyrosine
      antibody confirmed that the 100 kD tyrosine phosphorylated protein was band 3. In
      the sickle cell disease group, the band 3 tyrosine phosphorylation varied from 2-
      to 10-fold increase compared to control (x +/- SD; SS = 7.8- +/- 2.7-fold; SC =
      3.8- +/- 1.3-fold; Sbeta = 5.2- +/- 2.0-fold). It was also higher in the beta
      thalassemic group (beta-thal = 4.3- +/- 3.7-fold). There was no significant
      difference in tyrosine phosphorylation among the various groups tested, except
      when we compared the phosphorylation in intact red cells of patients with sickle
      cell anemia and hemoglobinopathy SC (U = 6, P < 0.02). The tyrosine
      phosphorylation of band 3 was increased in hemoglobinopathies even in the absence
      of high reticulocyte count. At least two mechanisms might be involved in the
      increased tyrosine phosphorylation of band 3 in these hemoglobin disorders,
      probably related to the endogenous reactive oxygen intermediates generated by the
      abnormal erythrocyte: an inhibition of protein tyrosine phosphatase activity or
      an activation of the protein tyrosine kinase p72syk.

PMID- 9662276
TI  - Solitary extramedullary plasmacytoma in the retroperitoneum.
AB  - Solitary extramedullary plasmacytoma is an uncommon neoplasm and occurs most
      frequently in the upper respiratory tract. Herein, we reported a solitary
      extramedullary plasmacytoma in the retroperitoneum. A 28-year-old man presented
      with obstructive jaundice and a retroperitoneal tumor. Ultrasound-guided biopsy
      confirmed that the lesion was a plasma cell neoplasm. A detailed investigation
      showed that no other sites were involved. The tumor got a moderate reduction
      following local irradiation, and a complete remission was achieved after 12
      courses of adjuvant chemotherapy. Therefore, the possibility of a solitary
      extramedullary plasmacytoma should be considered in the differential diagnosis of
      obstructive jaundice without a history of multiple myeloma.

PMID- 9662277
TI  - Chronic lymphocytic leukemia remission following extra corporeal shock wave
      lithotripsy for urinary calculi.
AB  - Herein we report on a patient with chronic lymphocytic leukemia (CLL) who entered
      a long-term remission following shock wave lithotripsy (SWL) for a left proximal
      ureteral stone. In addition, we include data on the effect of SWL on in vitro and
      in vivo human lymphocyte subpopulations, and discuss the possible mechanisms of
      this observation.

PMID- 9662278
TI  - Sensitive detection technique of myeloperoxidase precursor protein by flow
      cytometry with monoclonal antibodies.
AB  - This report describes the analysis of culture cells and blast cells separated
      from the heparinized bone marrow and whole blood of patients with acute leukemias
      by means of a density-gradient technique (Ficoll-sodium metrizoate d = 1.077
      g/cm3). Cell-surface antigens were analyzed by a fluorescence-activated cell
      sorter using a panel of monoclonal antibodies (MAbs). The blast cells and culture
      cells were fixed by 3% paraformaldehyde in phosphate-buffered saline. A low level
      of expression of MPO precursor protein was found in THP-1. K-562 and HEL, MEG-01,
      erythro-megakaryocytic leukemia cell lines, Jurkat, MOLT-3, MOLT-4, RPM18402, ATL
      5, T-cell leukemia cell lines, Raji, Daudi. BALL-1, B-cell leukemia cell lines,
      and AGNK1 showed negative reaction. The de novo MPO-negative acute leukemias,
      middle level of expression of MPO precursor protein, was found in the blasts of
      MPO-negative AML (AML, M0), which coexpressed CD13, CD33, CD34, and CD38. A high
      level of expression of MPO protein was found in all cases of AML, M1, and M2. The
      MPO expression was not found in all cases of acute lymphoblastic leukemia. The
      highest level of MPO expression was found in cases of AML, M3, and AML, M3v,
      suggesting the diagnostic value for this type of leukemia. The detection of MPO
      precursor protein by flow cytometric analysis with monoclonal antibodies is
      essential for the determination of lineage and precise diagnosis of acute
      unclassifiable leukemia, and should contribute substantially to the development
      of an effective form of therapy and cure.

PMID- 9662279
TI  - Waldenstrom's macroglobulinemia resulting from localized gastric
      lymphoplasmacytoid lymphoma.
AB  - A patient with a high level serum monoclonal IgM lambda paraprotein (3,850 mg/dL)
      was found to have a mass infiltrating the gastric mucosa. Gastric biopsy with
      immunohistochemical stains showed a B-cell lymphoplasmacytoid infiltrate
      expressing IgM lambda, consistent with Waldenstrom's macroglobulinemia. The
      patient's response to gastric radiation indicated that the primary source of the
      macroglobulinemia was the stomach. This is an extremely rare presentation, with
      only six other reported cases of this entity with gastric involvement.

PMID- 9662280
TI  - Mesenteric artery thrombosis: a case report of combined protein S and protein C
      deficiency.
AB  - Individuals with more than one defect in natural coagulant/anticoagulant systems
      have been postulated to be at an increased risk for thrombotic events. We report
      a case of combined protein S and C deficiency in a young woman, which resulted in
      fatal arterial mesenteric thrombosis. The role of coagulation defects in arterial
      thrombosis is discussed.

PMID- 9662281
TI  - Simultaneous occurrence of lupus anticoagulant and factor VIII inhibitors in
      hemophilia.

PMID- 9662282
TI  - Polycythemia vera in a patient with acquired immunodeficiency syndrome.

PMID- 9662283
TI  - Prothrombin gene 20210 G-A mutation in the Turkish population.

PMID- 9662284
TI  - Elevated beta 2-microglobulin in lymphorrhea from immunoblastic lymphoma.

PMID- 9662285
TI  - Are sickle cell disease patients with stroke genetically predisposed to the event
      by inheriting a tendency to high tumor necrosis factor levels?

PMID- 9662286
TI  - Usefulness of IPSS for the patients with refractory anemia.

PMID- 9662287
TI  - Vibrio vulnificus sepsis associated with coincidental diagnosis of acute myeloid
      leukemia.

PMID- 9662288
TI  - The effect of route of delivery on regression of abnormal cervical cytologic
      findings in the postpartum period.
AB  - OBJECTIVES: We sought to determine whether pregnant women with abnormal
      antepartum cervical cytologic findings differ in their postpartum rates of
      regression with respect to mode of delivery. STUDY DESIGN: Between 1990 and 1997,
      446 pregnant women with antepartum abnormal cervical cytologic findings were
      identified. Complete demographic, clinical, and cytologic reports were available
      for 138 women. Papanicolaou smear data were collected and separated into three
      groups by use of the Bethesda classification system (atypical squamous cells of
      undetermined significance, low-grade squamous intraepithelial cells, and high
      grade intraepithelial cells). Postpartum regression rates of antepartum
      Papanicolaou smears, with respect to degree of squamous epithelial cell
      abnormality and mode of delivery, were analyzed by Fisher's exact and Wilcoxon
      rank sum tests. RESULTS: Of the 138 women, 109 (79%) were delivered vaginally and
      29 (21%) by cesarean section. No statistically significant difference was found
      between women delivered vaginally and those delivered by cesarean section with
      respect to age, parity, and smoking history within the three groups (atypical
      squamous cells of undetermined significance, low-grade squamous intraepithelial
      cells, and high-grade squamous intraepithelial cells). The overall postpartum
      regression rate for the 59 women with antepartum high-grade squamous
      intraepithelial cells was 48%. Of the 47 women with high-grade squamous
      intraepithelial cells who were delivered vaginally, 28 showed regression in the
      postpartum period versus none of the 12 women delivered by cesarean section (60%
      vs 0%, p < 0.0002). CONCLUSION: Postpartum spontaneous regression of Papanicolaou
      smears consistent with high-grade squamous intraepithelial cells occurs with
      increased frequency among women who are delivered vaginally versus by cesarean
      section.

PMID- 9662289
TI  - Stillbirth evaluation: what tests are needed?
AB  - OBJECTIVE: We sought to investigate what aspects of the stillbirth evaluation are
      considered to be essential and what tests can potentially be eliminated. STUDY
      DESIGN: A retrospective analysis of 745 stillbirths occurring from January 1990
      to December 1994 was conducted. A stillbirth was defined by an estimated
      gestational age >20 weeks' gestational age or fetal weight >500 gm. We attempted
      to arrive at an apparent cause for each stillbirth after evaluation of genetic or
      chromosomal abnormalities, obstetric history, maternal medical illnesses,
      laboratory tests, autopsy findings, and placental pathologic conditions. RESULTS:
      We found that the most important aspects of stillbirth evaluation were placental
      pathologic conditions and autopsy. When the placenta was examined, a significant
      abnormality was detected in 30% (160 of 529) of the cases. When autopsy was
      performed, only 31% of fetal deaths (142 of 462) were unexplained; however, when
      no autopsy was performed, 44% (125 of 283) were unexplained (p = 0.0002). The
      following laboratory evaluations that were routinely performed were found to
      yield little definitive information: antinuclear antibody testing, Kleihauer
      Betke test, and screening for congenital infections (toxoplasmosis, other
      viruses, rubella, cytomegalovirus, and herpes simplex virus). Overall, 36% (267
      of 745) of stillbirths still remained unexplained despite a thorough evaluation
      in most cases. CONCLUSION: The causes of stillbirth are many and varied, with a
      large proportion having no obvious cause. As this study demonstrates, certain
      laboratory tests can be eliminated in the workup of fetal death. In the
      evaluation of stillbirth a complete systematic method that incorporates placental
      pathologic conditions, as well as autopsy findings, should prove to be
      beneficial.

PMID- 9662290
TI  - Obstetric maneuvers for shoulder dystocia and associated fetal morbidity.
AB  - OBJECTIVE: We sought to determine the fetal injury rate associated with shoulder
      dystocia and to determine whether there is a higher rate of brachial plexus
      injury or bone fracture when fetal manipulation techniques are required for
      delivery. STUDY DESIGN: A retrospective review of 285 cases of shoulder dystocia
      that occurred between January 1991 and December 1995 was performed. The type,
      sequence, and combination of obstetric maneuvers used to relieve the shoulder
      dystocia were noted. These cases were divided into two groups, as follows: (1)
      those resolved with McRoberts' maneuver, suprapubic pressure, or proctoepisiotomy
      or a combination of these and (2) those that required the addition of direct
      fetal manipulative maneuvers (Woods, posterior arm, or Zavanelli). Fetal injury
      was defined as the occurrence of brachial plexus palsy, clavicular fracture,
      humeral fracture, or fetal death caused by asphyxial complications. RESULTS: The
      fetal injury rate was 24.9% (71/285), including 48 (16.8%) brachial plexus
      palsies, 27 (9.5%) clavicular fractures, and 12 (4.2%) humeral fractures. Sixteen
      infants had both nerve injury and bone fracture. Four (8.9%) brachial plexus
      palsies had documented persistence at 1 year of follow-up. One neonatal death
      occurred at age 3 months after an episode of hypoxic ischemic encephalopathy. The
      incidence of bone fracture was not higher when direct fetal manipulation was
      required: 21 of 127 (16.5%) versus 18 of 158 (11.4%), p = 0.21. The incidence of
      brachial plexus palsy was also similar in both groups (27/127 vs 21/158, p =
      0.1). CONCLUSIONS: Direct fetal manipulation techniques used to alleviate
      shoulder dystocia are not associated with an increased rate of bone fracture or
      brachial plexus injury.

PMID- 9662291
TI  - Adenocarcinoma of the uterine cervix metastatic to lymph nodes.
AB  - OBJECTIVE: We set out to evaluate the prognostic factors in cervical
      adenocarcinoma metastatic to lymph nodes. STUDY DESIGN: We performed a
      retrospective review of 40 patients with cervical adenocarcinoma and lymph node
      metastasis from 1976 to 1996. RESULTS: Thirty-four patients had adenocarcinoma,
      and six had adenosquamous carcinoma. Median survival was 50 months. The median
      survival for patients with stage I disease was 69 months. Stage at diagnosis,
      treatment with radical hysterectomy, and receiving adjuvant therapy were
      associated with prolonged survival. A trend toward improved survival was noted
      with the use of concurrent radiation and chemotherapy as an adjuvant therapy.
      CONCLUSIONS: Adenocarcinoma metastatic to the lymph nodes does not have a
      uniformly poor prognosis, especially with early-stage disease. Improved survival
      was observed with the use of adjuvant therapy, specifically the use of combined
      chemotherapy and radiation after radical hysterectomy. The optimal therapy in
      this setting is yet to be determined.

PMID- 9662292
TI  - Human chorionic gonadotropin production by the pituitary gland in a premenopausal
      woman.
AB  - OBJECTIVE: Our purpose was to investigate the source of human chorionic
      gonadotropin production in a nonpregnant, premenopausal woman. STUDY DESIGN: A
      case of human chorionic gonadotropin production by the pituitary gland in a
      premenopausal woman is described. RESULTS: Our results confirm that a
      biologically active human chorionic gonadotropin-like molecule was secreted in a
      nonpregnant woman. CONCLUSIONS: Our results indicate that the pituitary gland was
      the most likely source of human chorionic gonadotropin production.

PMID- 9662293
TI  - Bartholinitis after vulvovaginal surgery.
AB  - OBJECTIVES: The object of the study was to determine whether obstruction of the
      Bartholin gland duct after vulvovaginal surgery is a cause of Bartholin gland
      infections or cysts. STUDY DESIGN: The records of patients with vulvovaginal
      surgical procedures performed by me between 1983 and 1997 were reviewed for
      evidence of a Bartholin gland infection or cyst formation. RESULTS: A
      postoperative Bartholin gland infection occurred in 2 of 217 patients with
      posterior colporrhaphy (with or without vault suspension) and 1 of 14 patients
      with partial vestibulectomy for vestibulitis. No patient had a chronic Bartholin
      cyst develop. CONCLUSIONS: Bartholin gland infections and Bartholin cysts are
      uncommon occurrences after surgical procedures that have the potential to
      obstruct the Bartholin duct.

PMID- 9662295
TI  - Preliminary report on the treatment of endometriosis with low-dose mifepristone
      (RU 486).
AB  - OBJECTIVE: We have previously shown that treatment with mifepristone, 50 to 100
      mg daily, results in amenorrhea, anovulation, and symptomatic improvement in
      women with endometriosis. In this study we lowered the dose to 5 mg daily to
      determine whether clinical efficacy is altered without other adverse actions.
      STUDY DESIGN: After a baseline cycle, seven women with endometriosis were given
      mifepristone, 5 mg daily, for 6 months. Daily symptom inventories were recorded.
      Laparoscopy was performed during the sixth month of therapy. RESULTS: Pelvic pain
      improved in six of seven patients. Cyclic bleeding ceased in all patients, but
      four of the seven patients complained of irregular bleeding. Surgical staging at
      the conclusion of the study (five of seven patients) did not detect a change in
      endometriosis. CONCLUSIONS: Mifepristone, 5 mg daily, resulted in symptomatic
      improvement, but did not stabilize the endometrium. From our experience with
      three doses of mifepristone, we would recommend a dose of 50 mg be used for
      continued investigations.

PMID- 9662294
TI  - Abnormalities detected on transvaginal ultrasonography in tamoxifen-treated
      postmenopausal breast cancer patients may represent endometrial cystic atrophy.
AB  - OBJECTIVE: This study was conducted to examine the histopathologic changes in
      tamoxifen-treated postmenopausal patients with endometrial thickness > or = 5 mm
      with transvaginal ultrasonography. STUDY DESIGN: Thirty-five tamoxifen-treated
      postmenopausal breast cancer patients underwent transvaginal pelvic
      ultrasonography with endometrial thickness > or = 5 mm followed by either
      curettage-hysteroscopy (n = 24), or hysterectomy (n = 11). Endometrial
      histopathologic findings were examined. RESULTS: Overall, endometrial polyps were
      the most common histopathologic finding (23 of 35 patients). Endometrial cystic
      atrophy was uncommonly detected in patients undergoing curettage-hysteroscopy (1
      of 24 patients) compared with patients undergoing hysterectomy (9 of 11
      patients). No cases of endometrial cancer or hyperplasia were detected.
      CONCLUSIONS: Endometrial polyps were a frequent finding in tamoxifen-treated
      postmenopausal women who had endometrial thickness > or = 5 mm with the use of
      transvaginal ultrasonography. Endometrial cystic atrophy may explain "thickened
      endometrium" on transvaginal ultrasonography in this patient population with no
      evidence of endometrial polyps, hyperplasia, or adenocarcinoma after surgical
      evaluation.

PMID- 9662296
TI  - Managed health care and resident education.
AB  - OBJECTIVE: We wished to determine the impact of managed health care on resident
      education in obstetrics and gynecology. STUDY DESIGN: A multiquestion survey was
      mailed to program directors of the 267 obstetrics-gynecology resident training
      programs in the United States. The questions ascertained departmental philosophy
      regarding the role of obstetrician-gynecologists as primary care versus
      specialist physicians, the extent of involvement with managed health care
      companies, educational curriculum content, the effect of managed care on patient
      volume, faculty time available for resident teaching, and the effect of managed
      care on resident education. RESULTS: Completed surveys were received from 210
      (79%) program directors. One hundred twenty-six (63%) program directors responded
      that obstetrician-gynecologists should be primary care physicians for women, and
      120 (60%) believed that the role of subspecialists will be reduced in the near
      future. In 1996, 177 (94%) programs had managed care contracts; many (57%) had
      >20 contracts. All programs participate with other specialties to teach primary
      care to their residents. One hundred twelve (59%) programs have had a decrease in
      patient volume, prompting 90 (45%) programs to increase their number of teaching
      sites. Of concern, 54 (26%) program directors noted that managed care companies
      discourage but do not restrict resident participation in the care and treatment
      of managed care patients, and 41 (20%) programs had some restrictions placed on
      such resident involvement. Budgetary constraints have decreased resources to 97
      (47%) programs and threaten the time available for faculty teaching. CONCLUSIONS:
      Managed health care is having an effect on many resident teaching programs.
      Program directors are integrating managed care concepts into the educational
      curriculum and are negotiating with managed care organizations to involve
      residents in the care and treatment of managed care patients.

PMID- 9662297
TI  - The disclosure decision: concerns and issues of parents of children conceived
      through donor insemination.
AB  - OBJECTIVE: The purpose of our study was to examine the disclosure decision by
      parents of children conceived by donor insemination. STUDY DESIGN: A qualitative
      component of a self-administered questionnaire mailed to 184 couples who had
      become parents by donor insemination encouraged respondents to volunteer their
      written comments, concerns, or opinions about their disclosure decision. RESULTS:
      A total of 70 men and 86 women submitted written comments indicating that 54% did
      not plan to disclose the donor insemination treatment (nondisclosers), 30%
      indicated they would (disclosers), and 16% remained undecided. The only
      significant relationship between the disclosure decision and expressed concern
      was with regard to confidentiality and honesty (chi2 = 99.9, p < 0.05).
      CONCLUSIONS: Whether parents viewed the disclosure issue as one of honesty
      (disclosers) or confidentiality (nondisclosers) was the major determinant in the
      decision of whether to tell children about their donor insemination origin. There
      was no association between disclosure status or gender and expressed concerns
      about parenting, children, or family relations.

PMID- 9662298
TI  - Intergenerational gamete donation: ethical and societal implications.
AB  - Cases of daughter-to-mother oocyte donation, niece-to-aunt oocyte donation, and
      father-to-son sperm donation are presented. Comparisons to sibling gamete
      donation and organ donation, potential ethical conflicts, and societal
      implications are examined in an attempt to aid decision making when these
      procedures are requested.

PMID- 9662299
TI  - Primary vaginal melanoma: thirteen-year disease-free survival after wide local
      excision and review of recent literature.
AB  - OBJECTIVES: We present a case report of a woman who has survived 13 years after
      conservative treatment with wide excision for vaginal melanoma and review and
      evaluate the literature on this disease since the last metaanalysis in 1989.
      STUDY DESIGN: A database literature search along with cross referencing from
      related articles uncovered 66 patients who were reported to have vaginal melanoma
      since 1989 with adequate information for our analysis. We add to this one
      original case reported by us. Where information was available, we analyzed
      outcomes on these cases on the basis of patient age, tumor thickness, tumor size,
      and treatment. RESULTS: The patient we describe is only the eighteenth reported
      patient to survive vaginal melanoma 5 years and only the third to survive for 10
      years. Of the 67 patients in our overall review, mean age at the time of
      diagnosis was 62 years. Patients with tumor size < 3 cm had a mean survival of 41
      months compared with 12 months for those with tumor size > or = 3 cm (p <
      0.0024). Tumor thickness did not significantly affect patient survival at any of
      the depths analyzed, although there was a tendency toward significance at depths
      > 8 mm (p < 0.0778). There also was no significant difference in patient outcome
      among five treatment groups: (1) wide excision, (2) radical surgery, (3)
      radiation therapy, (4) wide excision plus radiation therapy, and (5) other.
      CONCLUSION: Tumor size appears to affect survival in patients with vaginal
      melanoma. Tumor thickness, at least at the levels at which vaginal melanomas are
      currently being diagnosed, does not seem to affect survival. Because no single
      treatment is clearly preferable, we suggest conservative resection where
      possible. We find it difficult to support radical surgery as primary treatment
      for vaginal melanoma unless necessary to achieve clear tumor margins. Radiation
      therapy appears to offer results comparable to those of surgery.

PMID- 9662300
TI  - Real-time ultrasonographically guided removal of nonpalpable and intramuscular
      Norplant capsules.
AB  - OBJECTIVE: Our purpose was to describe the techniques we have developed to remove
      nonpalpable subcutaneous and intramuscular Norplant capsules with the patient
      under local anesthesia and with use of real-time ultrasonographic guidance in an
      office setting. STUDY DESIGN: This was a noncomparative, descriptive study of our
      experiences with 27 women with 64 deep Norplant capsules. RESULTS: Twenty-four
      women had all their nonpalpable and intramuscular implants removed under real
      time ultrasonographic guidance with no complications. One woman was not a
      candidate, one was lost to follow-up, and another elected to retain her last
      implant. CONCLUSION: Real-time ultrasonographically guided procedures can be
      performed with the patient under local anesthesia in an office setting and can
      reduce the number of operative procedures necessary to remove nonpalpable and
      intramuscular Norplant capsules.

PMID- 9662301
TI  - Ultrasonographic detection of ureteral jets in normal pregnancy.
AB  - OBJECTIVE: Our purpose was to determine the impact of normal physiologic
      urodynamic alterations of pregnancy on the detection of ureteral jets into the
      bladder with use of transabdominal color Doppler ultrasonography. STUDY DESIGN:
      We conducted a prospective cohort study of 125 healthy asymptomatic gravid women
      without any history of past or current renal disease, all with singleton
      pregnancies between 13.4 and 37.7 weeks' gestation. Right and left ureteral jets
      were recorded over a 5-minute period with use of color Doppler transabdominal
      ultrasonography and a full bladder. Each kidney was graded by the severity of the
      hydronephrosis. No hydronephrosis was grade 0, mild hydronephrosis was grade 1,
      and moderate hydronephrosis was grade 2. There were no cases of severe
      hydronephrosis. RESULTS: There were 56 grade 0 cases on the right versus 93 grade
      0 cases on the left (p < 0.0001), 53 versus 30 grade 1 cases (right vs left, p <
      0.003) and 16 versus 2 grade 2 cases (right vs left, p < 0.0009). In the subgroup
      where both kidneys were grade 0 the mean number of right ureteral jets 5 mm was
      14.7 versus 15.1 for the left ureteral jets (p = 0.73). In the grade 1 subgroup
      mean right versus left ureteral jets was 15.4 versus 16.6 (p = 0.65). For the
      grade 2 subgroup mean right versus left ureteral jets was 15.5 versus 21.0 (p =
      0.32). There were 4 of 125 unilateral absent ureteral jets on the right versus 0
      of 125 on the left (p = 0.122). CONCLUSION: Our data demonstrate that ureteral
      jets can be readily detected during pregnancy independent of the gestational age.
      In addition, it does not appear that the physiologic urodynamic alterations of
      pregnancy affect the frequency or symmetry of ureteral jets. Thus identification
      of ureteral jets can be used in the workup of suspected urolithiasis in pregnant
      patients.

PMID- 9662302
TI  - Three-dimensional ultrasonography in obstetrics and gynecology: preliminary
      experience.
AB  - OBJECTIVE: Technologic advances in ultrasonographic imaging have revolutionized
      the management of women's health care. We recently began to evaluate the clinical
      applications of three-dimensional ultrasonography. STUDY DESIGN: This study
      prospectively evaluated 161 obstetric and gynecologic patients. Both two- and
      three-dimensional imaging data were acquired from real-time ultrasonography.
      Three orthogonal planes were displayed on a monitor and were used to create the
      rendered three-dimensional images. RESULTS: To date, 201 three-dimensional
      ultrasonographic studies have been performed, 165 transabdominally and 36
      transvaginally. Transabdominally, an average of eight acquisitions per patient
      were obtained. Of the clinically suspected abnormalities, 29 of 32 (91%) were
      confirmed by three-dimensional imaging. Three of 32 (9%) improved the diagnostic
      capabilities or changed the diagnosis. Of the 36 transvaginal studies, an average
      of four acquisitions per patient were done. Thirty (83%) of these patients had
      suspected abnormalities and all were confirmed. CONCLUSIONS: Three-dimensional
      ultrasonographic imaging appears to be highly promising in the clinical setting.

PMID- 9662303
TI  - Lowering the cesarean section rate in a private hospital: comparison of
      individual physicians' rates, risk factors, and outcomes.
AB  - OBJECTIVE: Our purpose was to compare the practice patterns and outcomes of
      physicians delivering in our institution to identify risk factors and management
      techniques that could explain the differences in individual cesarean section
      rates. STUDY DESIGN: We retrospectively reviewed detailed computerized delivery
      records (n = 16,230) collected from May 16, 1988, to July 30, 1995. We excluded
      physicians who had <100 deliveries at our institution during the study period.
      The physicians were divided into two groups depending on whether their individual
      cesarean section rates were greater than (control group) or less than 15% (target
      group). Various cesarean section rates, risk factors for abdominal delivery,
      labor management techniques, and neonatal outcome parameters were calculated for
      each group. The cesarean section rates of the two groups were analyzed by year to
      assess changes. RESULTS: As expected by study design, the overall cesarean
      section rate was markedly different between the two groups (13.8% vs 23.8%). In
      addition, the primary, repeat, primigravid, and multiparous cesarean section
      rates were all lower for the target group. The rates of cesarean section for
      fetal distress (1.5% vs 3.3%) and cephalopelvic disproportion (5.3% vs 8.5%) were
      also significantly less in the target group. The rates of breech presentation,
      third-trimester bleeding, and active herpes cesarean sections were not lower. The
      control group had more postterm (8.6% vs 14.7%) and >4000 gm infants (12.0% vs
      13.7%) but similar numbers of low birth weight, multiple gestation, and preterm
      infants. The target group used more epidural anesthesia, oxytocin induction, and
      trial vaginal births after cesarean delivery and more successful trial vaginal
      births after cesarean sections. Over the study period the cesarean section rate
      in the target group remained unchanged, whereas it steadily declined in the
      control group. CONCLUSIONS: Individual physician's lower cesarean sections are
      primarily obtained by labor management and attempting vaginal birth after
      cesarean delivery. These practice patterns did not appear to lead to any increase
      in perinatal morbidity or mortality. Efforts to lower cesarean section rates of
      individual practitioners should focus on the areas of fetal distress,
      cephalopelvic disproportion, and repeat cesarean section.

PMID- 9662304
TI  - Is there an association between water baths during labor and the development of
      chorioamnionitis or endometritis?
AB  - OBJECTIVE: Our purpose was to determine whether water baths during labor are
      associated with the development of chorioamnionitis or endometritis. STUDY
      DESIGN: One hundred ten cases of chorioamnionitis or endometritis and 97 controls
      were identified among singleton term gestations from the University of California
      at San Francisco perinatal database. Medical record review and patient interviews
      provided information on membrane rupture, history of bathing during labor, and
      relaxation and pain relief perceived by patients who experienced water bathing
      during labor. RESULTS: There was no statistically significant association between
      water baths during labor and the occurrence of chorioamnionitis or endometritis
      (odds ratio 0.93 [95% confidence interval 0.53 to 1.63]). CONCLUSIONS: Water
      baths during labor are not associated with chorioamnionitis or endometritis.

PMID- 9662305
TI  - Obstetrician-gynecologists as primary care physicians: the Oregon experience-
      early perceptions regarding the effects of legislative action.
AB  - OBJECTIVE: Our purpose was to assess whether legislative action influenced the
      role of obstetrician-gynecologists as primary care physicians. STUDY DESIGN: An
      observational study was performed on the basis of a questionnaire sent to 410
      obstetrician-gynecologists and 27 medical directors of managed-care
      organizations. RESULTS: Of 67% of obstetrician-gynecologists and 96% of medical
      directors who responded, there was agreement as to the content of primary care,
      but a minority (38%) of obstetrician-gynecologists identified themselves as
      primary care providers. A minority of medical directors (35%) felt that
      obstetrician-gynecologists should serve in that role. Both obstetrician
      gynecologists and medical directors felt that legislation had little impact.
      CONCLUSION: The reticence of obstetrician-gynecologists to assume a major role in
      primary care appears to be the result of an uneasiness with accepting a more
      comprehensive role in patient management and gatekeeping. They appear comfortable
      with the more traditional roles but feel that training and experience has not
      prepared them well for the management of more complex medical problems.

PMID- 9662306
TI  - Gynecologic surgery: an imperiled ballet. Presidential address.

PMID- 9662307
TI  - Is human papillomavirus testing an effective triage method for detection of high
      grade (grade 2 or 3) cervical intraepithelial neoplasia?
AB  - OBJECTIVE: Our purpose was to assess the usefulness of the polymerase chain
      reaction assay for detection of human papillomavirus infection for prognostic
      value in the triage strategies for high-grade (grade 2 or 3) cervical
      intraepithelial neoplasia in women referred for colposcopy after abnormal
      Papanicolaou smears. STUDY DESIGN: A total of 1007 women referred to a
      colposcopic clinic providing care for an indigent population were studied. Four
      hundred fifty-four women were referred after two Papanicolaou smears reported as
      atypical squamous cells of undetermined significance or low grade-squamous
      cervical intraepithelial lesion, and 553 were referred after a single smear
      reported as high-grade squamous intraepithelial lesion. All women had a cervical
      smear, colposcopy-directed biopsy, and endocervical curettage performed. A sample
      for human papillomavirus deoxyribonucleic acid detection by polymerase chain
      reaction was obtained. RESULTS: High-risk human papillomavirus types were
      detected in 463 (46%) of 1007 women studied. There was a significant increase of
      the frequency of high-risk human papillomavirus by the increasing severity of
      biopsy findings ranging from 32.7% in women without cervical intraepithelial
      neoplasia on biopsy to 60% in women having grade 2 or 3 on the biopsy specimen.
      Women having a negative Papanicolaou smear found to have high-risk human
      papillomavirus deoxyribonucleic acid at the time of colposcopy had a
      significantly higher rate of grade 2 or 3 cervical intraepithelial neoplasia on
      the biopsy specimen than did women without high-risk human papillomavirus. There
      was no such difference observed in women with a cytologic finding of low- or high
      grade squamous intraepithelial lesions at the time of colposcopy. The polymerase
      chain reaction assay appears to be more sensitive than the commercial human
      papillomavirus profile test. The positive predictive value for grade 2 or 3
      cervical intraepithelial neoplasia of both tests was similar (21.7% and 22.8%,
      respectively). CONCLUSION: The human papillomavirus is associated with high-grade
      cervical intraepithelial neoplasia, but the screening for human papillomavirus
      deoxyribonucleic acid does not have prognostic value in women reported as having
      atypical squamous cells of undetermined significance or low-grade squamous
      intraepithelial lesions on two precolposcopy Papanicolaou smears.

PMID- 9662308
TI  - Open surgical biopsy for nonpalpable mammographic abnormalities: still an option
      compared with core needle biopsy.
AB  - OBJECTIVE: Our purpose was to present information about open surgical biopsy. It
      is hoped that this will be helpful when reviewing information about core needle
      biopsy STUDY DESIGN: Review of 461 open surgical biopsies for nonpalpable
      mammographic abnormalities was performed. All patients were managed by the
      Women's Health Center of Logansport. Core needle biopsy data came from the
      literature. RESULTS: Open surgical biopsy compared favorably to core needle
      biopsy with regard to accuracy, cost, patient convenience, recovery, adequacy of
      specimen, identification of primary site, and cosmetics. CONCLUSION: Despite core
      needle biopsy marketing, open surgical biopsy has its advantages and should not
      be relegated to the museum.

PMID- 9662309
TI  - Screening for gestational diabetes mellitus in adolescent pregnancies.
AB  - OBJECTIVE: Our purpose was to determine the incidence of gestational diabetes
      mellitus in an adolescent population and to determine the cost of screening.
      STUDY DESIGN: A retrospective review of 509 adolescent pregnancies was performed.
      The incidence of gestational diabetes mellitus was determined and the cost of
      screening analyzed. RESULTS: Five hundred nine adolescent pregnancies were
      screened for gestational diabetes mellitus with a 1-hour, 50 gm oral glucose
      challenge test. Twenty-three of the screens (4.5%) had positive results at a
      plasma glucose level of > or = 140 mg/dl. Three-hour 100 gm oral glucose
      tolerance tests were performed on screen-positive women, six of whom were
      diagnosed with gestational diabetes mellitus, for an incidence of 1.18%. The cost
      per case diagnosed was $2733. CONCLUSIONS: The incidence of gestational diabetes
      mellitus in an adolescent population is low. The cost of universal screening may
      be prohibitive in this population. Large prospective studies are needed to better
      analyze outcome data and efficacy of screening in adolescent pregnancies.

PMID- 9662310
TI  - Guidelines to determine the role of laparoscopically assisted vaginal
      hysterectomy.

PMID- 9662311
TI  - Human immunodeficiency virus infection and women: a survey of missed
      opportunities for testing and diagnosis.
AB  - OBJECTIVE: Our purpose was to describe factors that prompted testing of women
      infected with the human immunodeficiency virus and health encounters in which
      missed opportunities for diagnosis occurred. STUDY DESIGN: An observational
      investigation of 81 human immunodeficiency virus-infected women in the Chicago
      area was performed by means of an interviewer-administered survey. Patient
      demographic data, health history, and health care contacts were elicited.
      RESULTS: Sixty-five women (80%) had at least one documented missed opportunity
      during the 12 months before their diagnosis. Seventy-eight percent of those women
      with missed opportunities had them occur at reproductive health encounters. Of 25
      pregnant women pregnant in the year before their eventual diagnosis, 12 failed to
      be diagnosed during that pregnancy. CONCLUSION: Despite visits to reproductive
      health care providers, the presence of symptoms suspicious for human
      immunodeficiency virus disease, high-risk behaviors, and even specific requests
      for testing by many of the women, numerous opportunities for the earlier
      diagnosis of human immunodeficiency virus infection were missed.

PMID- 9662312
TI  - Medically sound, cost-effective treatment for pelvic inflammatory disease and
      tuboovarian abscess.
AB  - OBJECTIVE: Our purpose was to determine the clinical effectiveness and cost
      effectiveness of three antibiotic regimens for the treatment of pelvic
      inflammatory disease and tuboovarian abscess. STUDY DESIGN: A review of all
      patients' hospitalized at Hutzel Hospital, Detroit, Michigan, for treatment of
      pelvic inflammatory disease and tuboovarian abscess between Jan. 1, 1993, and
      April 30, 1997, was performed. Demographic data, antibiotic choices, changes in
      therapy, operative interventions, and cost of therapy were assessed. RESULTS: Two
      hundred three patients were admitted for treatment of pelvic inflammatory disease
      during the study period. We were able to evaluate the clinical efficacy of
      antibiotic treatment in 179 patients, including 105 patients with pelvic
      inflammatory disease alone (uncomplicated pelvic inflammatory disease) and 74
      women whose infection was complicated by tuboovarian abscess. The three
      antibiotic regimens evaluated were cefotetan plus doxycycline, clindamycin plus
      gentamicin, and ampicillin plus clindamycin plus gentamicin. All regimens
      demonstrated comparable efficacy in treating uncomplicated genital tract
      infections. Ampicillin plus clindamycin plus gentamicin was significantly better
      than clindamycin plus gentamicin and cefotetan plus doxycycline in treatment of
      tuboovarian abscess (p = 0.001). Fifteen women with tuboovarian abscess responded
      to a change to ampicillin plus gentamicin plus clindamycin antibiotic therapy
      alone. The hospital stay was prolonged by approximately 3 days in women failing
      to respond to initial antibiotic therapy, and operative interventions were common
      in this group of patients. CONCLUSIONS: Cefotetan plus oral doxycycline is the
      most cost-effective regimen for treating uncomplicated pelvic inflammatory
      disease, whereas triple-antibiotic therapy is the treatment of choice in women
      with tuboovarian abscess.

PMID- 9662313
TI  - Management of pregnancies beyond forty-one weeks' gestation with an unfavorable
      cervix.
AB  - OBJECTIVE: Our purpose was to determine the optimal management of pregnancies
      beyond 41 weeks' gestation with a cervix unfavorable for induction. STUDY DESIGN:
      All uncomplicated pregnancies that reached 41 weeks' gestation with a Bishop
      score of < or = 4 were randomly assigned to one of three groups: (1) daily
      cervical examinations, (2) daily membrane stripping, or (3) daily placement of
      prostaglandin gel until 42 weeks. RESULTS: In 105 pregnancies the Bishop score on
      admission to labor and delivery was significantly greater in the groups receiving
      prostaglandin or stripping of the membranes versus the control group, whereas the
      converse was time of gestational age at delivery (p = 0.0001). Fewer patients
      required induction in the two treatment groups (20%, 17%) versus the control
      (69%) patients (p < 0.0001). CONCLUSIONS: Daily membrane stripping or daily
      placement of prostaglandin gel is successful in reducing the number of inductions
      at 42 weeks for postdatism.

PMID- 9662314
TI  - Identification of estrogen receptor protein and messenger ribonucleic acid in
      human spermatozoa.
AB  - OBJECTIVE: The processes leading to fertilization involve a series of sequential
      events including the deposition and transport of sperm in the female genital
      tract. It is becoming evident that spermatozoa in which a hyperactive state has
      been induced are more effective in both reaching and penetrating the oocyte. Many
      of the changes that spermatozoa undergo are the result of their ability to
      respond to the milieu of the female genital tract. In the presence of estrogen
      sperm have been shown to have increased their metabolic activity and flagellar
      activity and to have an increased ability to penetrate oocytes. Most important,
      these observed changes in sperm physiology occur quickly, suggesting a novel
      second-messenger system coupled to the estrogen receptor. Established effects of
      steroid hormones involve mediation of the signal through genomic expression.
      However, because it has not been definitively demonstrated whether the human
      sperm express the estrogen receptor, the mechanism by which estrogen exert its
      effect remains to be elucidated. STUDY DESIGN: The presence of estrogen receptors
      on human spermatozoa was investigated. Immunohistochemistry performed on human
      spermatozoa indicates that the estrogen receptors are located on the tailpiece.
      In addition, protein from human spermatozoa was isolated and subjected to Western
      blot analysis. RESULTS: Results indicate a single band of approximately 65 kd,
      similar to that of the native human estrogen receptor. Ribonucleic acid obtained
      from the human spermatozoa was reverse transcribed into deoxyribonucleic acid.
      With use of selected primers, this deoxyribonucleic acid was amplified by
      polymerase chain reaction. Resolution and examination of the expansion products
      demonstrated a single band of deoxyribonucleic acid of 450 bp, identical to that
      expected from the selected primers. The specificity of this reverse transcriptase
      polymerase chain reaction amplified deoxyribonucleic acid sequence was verified
      by Southern blotting. CONCLUSION: For the first time we provide evidence as to
      the expression of estrogen receptor by human spermatozoa.

PMID- 9662315
TI  - Three births after preimplantation genetic diagnosis for cystic fibrosis with
      sequential first and second polar body analysis.
AB  - OBJECTIVE: The purpose of this study was to determine the accuracy and
      feasibility of sequential polar body removal and analysis for preimplantation
      genetic diagnosis of mendelian disorders. STUDY DESIGN: Three couples with risk
      factors for cystic fibrosis had preimplantation genetic diagnosis with the use of
      sequential polar body analysis. After stimulation, oocytes were harvested and the
      first polar bodies were removed and analyzed on the day of aspiration. The
      following day, after fertilization, the second polar bodies were aspirated. Only
      embryos known to have inherited the normal maternal allele were transferred.
      RESULTS: All three couples had successful pregnancies resulting in the births of
      unaffected infants. CONCLUSIONS: Preimplantation diagnosis with the use of
      sequential polar body removal is feasible and can prevent the establishment of
      genetically abnormal pregnancies for couples at risk.

PMID- 9662316
TI  - The role of AT1 angiotensin receptor activation in the pathogenesis of
      preeclampsia.
AB  - OBJECTIVES: Preeclampsia is characterized by an increase in vascular tone
      associated with reduced uteroplacental flow. The nature of hypertension arising
      in pregnancy suggests that the abnormal increase in blood pressure is dependent
      on some humoral factor that mediates vasospasm. There is evidence that
      preeclampsia results from a breakdown in the balance between vasodilators such as
      prostacyclin and prostaglandin E2 and nitric oxide and the vasoconstrictors
      angiotensin II, thromboxane A2, serotonin, and endothelin. Furthermore, vascular
      reactivity to angiotensin II is greatly enhanced in preeclampsia as opposed to
      normal pregnancies. The increased vascular tone and the enhanced thromboxane
      production noted in preeclampsia may be mediated by the increased sensitivity to
      angiotensin II because angiotensin II coupled to an AT1 receptor is a potent
      vasoconstrictor and stimulates the accumulation of free arachidonic acid, the
      precursor of thromboxane and the prostaglandins. STUDY DESIGN: We used a rat
      model that has been shown to express the relevant clinical features of human
      preeclampsia to investigate the involvement of the AT1 angiotensin receptor in
      this pathologic condition. Pregnant rats were divided into three groups that were
      either infused with saline or endotoxin on the 14th day of pregnancy. One of the
      endotoxin-infused groups was further treated with the AT1-selective antagonist
      losartan from day 11 until day 19 of pregnancy. RESULTS: Perinatal outcome, blood
      pressure, and urine protein were monitored for each group. We observed that
      endotoxin infusion resulted in a decrease in pup weight and number of pups and
      caused an increase in mean arterial pressure as well as increased proteinuria
      when compared with saline solution-infused animals. In contrast, endotoxin
      infused rats receiving losartan exhibited no change in number or weight of pups
      when compared with control, and losartan tended to diminish the rise in mean
      arterial pressure. In addition, the increase in urinary protein excretion was
      completely blocked by losartan. CONCLUSIONS: Endotoxin infusion in pregnant rats
      appears to be a suitable model for the study of preeclampsia. Moreover, the
      angiotensin II-dependent activation of an AT1 receptor appears to mediate a
      portion of the pathophysiologic features associated with preeclampsia.

PMID- 9662317
TI  - Primed in situ labeling for rapid prenatal diagnosis.
AB  - OBJECTIVE: Our purpose was to assess the feasibility of primed in situ labeling
      for analysis of prenatal diagnostic specimens. STUDY DESIGN: Prenatal diagnostic
      specimens were chosen at random for analysis without knowledge of clinical
      indication. Primed in situ labeling with primers for chromosomes 18, 21, X, and Y
      was performed separate from conventional cytogenetic analyses. All clinical
      management considerations were based solely on conventional cytogenetic analyses.
      RESULTS: Forty-one samples were analyzed by primed in situ labeling: 35 direct
      preparations of chorionic villi and 6 uncultured amniotic fluid samples. In all
      cases analysis confirmed the particular chromosome number determined by
      conventional cytogenetic analysis. CONCLUSIONS: Although conventional metaphase
      studies remain the standard for prenatal cytogenetic analyses, the preliminary
      feasibility study finds primed in situ labeling to be a rapid and reliable
      adjunctive diagnostic technique applicable for prenatal diagnosis in certain
      clinical situations. Further study is needed to assess the efficacy of primed in
      situ labeling in comparison to fluorescent in situ hybridization and conventional
      cytogenetic analyses for prenatal diagnoses.

PMID- 9662318
TI  - Sequelae of unrecognized gestational diabetes.
AB  - OBJECTIVE: Prior studies have suggested that macrosomia is the only morbid
      condition associated with gestational diabetes and that this association is the
      result of confounding by maternal obesity rather than a result of gestational
      diabetes itself. We sought to determine whether unrecognized gestational diabetes
      is an independent predictor of macrosomia and other perinatal morbid conditions
      after controlling for confounding variables. STUDY DESIGN: A retrospective
      analysis of 472 consecutive cases of gestational diabetes diagnosed between 24
      and 30 weeks' gestation was undertaken including 16 prospectively identified but
      clinically unrecognized cases, 297 cases treated with diet alone, and 76 treated
      with diet plus insulin. Unrecognized cases were matched to 64 nondiabetic
      controls for race, age, body mass index, parity, pregnancy weight gain, and
      gestational age at delivery. RESULTS: In the unrecognized gestational diabetes
      group versus the nondiabetic control versus gestational diabetes diet groups
      rates of large for gestational age infants (44% vs 5% vs 9%, p < 0.0005),
      macrosomia (44% vs 8% vs 15%, p < 0.01), shoulder dystocia (19% vs 3% vs 3%, p <
      0.05), and birth trauma (25% vs 0% vs 0.3%, p < 0.001) were all significantly
      increased. These differences remained significant after controlling for maternal
      age, race, parity, body mass index, pregnancy weight gain, and gestational age at
      delivery. CONCLUSIONS: This study suggests that unrecognized gestational diabetes
      increases risks of large for gestational age infants, macrosomia, shoulder
      dystocia, and birth trauma independent of maternal obesity and other confounding
      variables. Clinical recognition and dietary control of gestational diabetes are
      associated with a reduction in these perinatal morbid conditions.

PMID- 9662319
TI  - Cervical ripening: a randomized comparison between intravaginal misoprostol and
      an intracervical balloon catheter combined with intravaginal dinoprostone.
AB  - OBJECTIVES: Our purpose was to compare the efficacy of intravaginal misoprostol
      and intracervical Foley catheter/intravaginal dinoprostone for cervical ripening.
      STUDY DESIGN: Patients admitted for induction of labor were randomized to receive
      intravaginal misoprostol 25 microg every 4 hours or intracervical Foley
      catheter/intravaginal dinoprostone 4 mg every 4 hours. Patients not entering
      active labor and having ruptured membranes or arrest of dilatation received
      intravenous oxytocin. RESULTS: Sixty-five patients received Foley
      catheter/dinoprostone gel and 62 patients received misoprostol. The mean time
      until cervical ripening was less in the catheter/gel group (7.5 +/- 3.4 vs 12.0
      +/- 5.9 hours, p < 0.01). The mean time until vaginal delivery was less in the
      catheter/gel group (17.4 +/- 6.9 vs 21.2 +/- 7.5 hours, p = 0.004). Among vaginal
      deliveries, more patients in the catheter/gel group delivered within 24 hours
      (90% vs 69%, p = 0.013). CONCLUSIONS: Intracervical Foley catheter/intravaginal
      dinoprostone was associated with more rapid cervical ripening, shorter induction
      to vaginal delivery interval, and greater number of vaginal deliveries within 24
      hours.

PMID- 9662320
TI  - Use of video eyeglasses to decrease anxiety among children undergoing genital
      examinations.
AB  - OBJECTIVE: Our purpose was to compare three techniques in their ability to
      decrease anxiety induced by the pelvic examination among children of different
      races. STUDY DESIGN: Eighty-nine subjects between 3 and 8 years old of white,
      African-American, and Hispanic race or ethnicity were randomly assigned to one of
      three distraction techniques that was used during the genital examination:
      passive play (being read to), active play (singing, blowing bubbles), or viewing
      a movie through video eyeglasses. Levels of vocalized distress, as well as
      distress expressed by physical behavior and emotional support requested, were
      directly observed and recorded. Children also reported their level of
      satisfaction at the end of the examination. Multivariate analysis of covariance
      was used to evaluate the independent effects of each technique and race while we
      controlled for confounding variables. RESULTS: Levels of physical distress were
      lowest among children who used video glasses and highest among those randomly
      assigned to passive play (p = 0.02). Children randomized to video glasses also
      expressed higher levels of satisfaction than those randomized to active (p =
      0.001) or passive (p = 0.05) play. No differences associated with race or
      ethnicity were detected. CONCLUSION: This study demonstrates that video glasses
      are more effective than active or passive play in reducing anxiety and improving
      satisfaction levels among children undergoing a genital examination.

PMID- 9662321
TI  - Comparison of the modified biophysical profile to a "new" biophysical profile
      incorporating the middle cerebral artery to umbilical artery velocity flow
      systolic/diastolic ratio.
AB  - OBJECTIVES: The objective of this study was to determine whether the addition of
      the middle cerebral to umbilical artery systolic/diastolic velocity waveform
      ratio to the modified biophysical profile would improve perinatal outcome in
      patients at high risk. STUDY DESIGN: A prospective, randomized outcome study of
      patients referred to the perinatal laboratory for antenatal surveillance was
      undertaken. Six hundred sixty-five patients were randomized to two antenatal
      surveillance protocols: group 1, modified biophysical profile; and group 2,
      modified biophysical profile plus evaluation of the middle cerebral artery to
      umbilical artery systolic/diastolic ratio. Patients were followed up serially and
      neonatal outcome data including gestational age at delivery, birth weight,
      incidence of cesarean section delivery for fetal distress, admission to the
      neonatal intensive care unit, days in the neonatal intensive care unit, and the
      presence of significant neonatal morbidity were tabulated. RESULTS: The total
      population showed no statistical difference in outcome parameters between groups
      1 and 2. However, a subgroup of patients evaluated for suspected uteroplacental
      insufficiency did show a significant reduction in caesarean section for fetal
      distress in group 2 patients. CONCLUSIONS: In a subgroup of patients at risk for
      uteroplacental insufficiency, the addition of the middle cerebral/umbilical
      artery ratio to an antenatal surveillance protocol should be expected to improve
      perinatal outcome.

PMID- 9662322
TI  - Analysis of three hundred fifteen ectopic pregnancies treated with single-dose
      methotrexate.
AB  - OBJECTIVES: The objective of this study was to review the largest single series
      of ectopic pregnancies treated with single-dose methotrexate reported to date.
      STUDY DESIGN: A review of 315 patients with unruptured ectopic pregnancies
      treated with single-dose methotrexate 50 mg/m2 from March 21, 1990, to March 1,
      1997, was performed. RESULTS: Overall 287 patients were successfully treated with
      methotrexate for a success rate of 90.1%. Six patients electively withdrew and
      requested surgery within 1 week of starting therapy. Excluding withdrawals the
      overall success rate was 92.9%. Ten patients with an ectopic pregnancy > 3.5 cm
      but < or = 4 cm in size were treated for a 90% success rate. Forty-four patients
      with positive ectopic cardiac activity were treated with an 87.5% success rate.
      CONCLUSIONS: This large series indicates that single-dose intramuscular
      methotrexate for treatment of ectopic pregnancy is associated with an excellent
      overall success rate.

PMID- 9662323
TI  - Doppler velocimetry determined redistribution of fetal blood flow: correlation
      with growth restriction in diamniotic monochorionic and dizygotic twins.
AB  - OBJECTIVE: Our purpose was to study fetal growth and blood flow distribution in
      diamniotic monochorionic compared with dizygotic (diamniotic dichorionic) twins
      by use of Doppler velocimetry of the umbilical artery and middle cerebral artery.
      STUDY DESIGN: Study candidates were divided into group A, consisting of 33 pairs
      (66 fetuses) of diamniotic monochorionic twins, and group B, 50 pairs (100
      fetuses) of diamniotic dichorionic twins. Diamniotic monochorionic placentation
      was confirmed by microscopic placental examination for group A. Diamniotic
      dichorionic placentation was ensured for group B by selecting only twins with
      different-sex pairs (dizygotic twins). Targeted ultrasonography with biometry was
      performed in each twin, and Doppler recordings of the umbilical artery and middle
      cerebral artery were obtained. Waveforms were analyzed and the systolic/diastolic
      ratio, the resistance index, and a measure of blood flow redistribution (brain
      sparing effect), the cerebral/placental ratio, was calculated for each fetus.
      Growth status at birth was assessed by the number of small-for-gestational-age
      infants (< or = 10th percentile), low-birth-weight infants (< or = 25th
      percentile), and percent of growth discordance between twins. Intertwin
      differences were assessed by delta values (value of larger twin minus value of
      smaller twin). RESULTS: Diamniotic monochorionic compared with dizygotic twins
      demonstrated a significantly greater probability of blood flow redistribution.
      For the study population as a whole, the brain-sparing effect was noted in 67% of
      small-for-gestational-age babies and only 7% of non-small-for-gestational-age
      infants (p < or = 0.001). For the diamniotic monochorionic pregnancies blood flow
      redistribution occurred in 6 of 10 small-for-gestational-age infants (60%) and 6
      of 46 non-small-for-gestational-age infants (13%). In the diamniotic
      monochorionic group small-for-gestational-age compared with non-small-for
      gestational-age infants were more likely to show blood flow redistribution, which
      was the result of significantly decreased resistance in the middle cerebral
      artery and significantly increased resistance in the umbilical artery. Small-for
      gestational-age infants (< or = 10th percentile) occurred much less frequently in
      the dizygotic group. Two of two small-for-gestational-age infants in the
      dizygotic group showed blood flow redistribution. Although the extremes of birth
      weight were more common in the diamniotic monochorionic group, both groups had
      relatively large numbers of small babies with birth weights in the lower 25th
      percentile (50.0% for diamniotic monochorionic and 44.0% for dizygotic twins, not
      significant). However, 42.3% (11/26) of diamniotic monochorionic twins who were
      in the low-birth-weight group showed blood flow redistribution compared with only
      3.3% (1/30) whose birth weights were > or = 25th percentile (p < or = 0.001). In
      the dizygotic twins 10% of lower-birth-weight infants redistributed blood flow
      compared with 1% in the higher-birth-weight group, a nonsignificant difference.
      Diamniotic monochorionic compared with dizygotic twins were delivered earlier
      (32.9 weeks vs 34.8 weeks, p < or = 0.001), were smaller (1832 gm vs 2304 gm, p <
      or = 0.001), showed higher birth weight discordance (29.8% vs 14%, p < or =
      0.05), and had greater numbers (19.7% vs 2.3%, p < or = 0.01) of infants at < or
      = 10th percentile birth weight. CONCLUSIONS: Diamniotic monochorionic twins from
      the lower-birth-weight groups more often show blood flow redistribution compared
      with dizygotic twins of similar low birth weights. Placental vascular connections
      and the attendant hemodynamic changes in the fetuses of diamniotic monochorionic
      twins probably account for this difference. Brain-sparing events occur commonly
      without clinical twin transfusion syndrome in this group. These findings have
      implications for management.

PMID- 9662325
TI  - Multiple pregnancy rates in in vitro fertilization: three embryos is too many for
      good-prognosis patients.

PMID- 9662324
TI  - Oral megadose methylprednisolone for idiopathic thrombocytopenic purpura.

PMID- 9662326
TI  - Postmenopausal bleeding: cost-effective evaluation.

PMID- 9662327
TI  - A new model of cell cycle-regulated transcription: repression of the cyclin A
      promoter by CDF-1 and anti-repression by E2F.
AB  - Cell cycle regulation of the cyclin A gene is determined by a bipartite repressor
      binding site in the region of the basal promoter, termed CDE-CHR, which also
      controls the expression of cell cycle genes upregulated in S or G2 (such as
      cdc25C). The CDE-CHR in the cyclin A promoter is recognized by both E2F complexes
      and CDF-1, but the contribution of each of these factors in cell cycle regulation
      is unknown. In the present study, we have introduced mutations into the cyclin A
      promoter which lead to either a loss or enhancement of E2F binding, while having
      only marginal effects on the interaction with CDF-1. Unlike mutants deficient for
      CDF-1 binding, promoter variants lacking E2F binding showed an unchanged
      repression in G0, thus identifying CDF-1 as the principal repressor of the cyclin
      A gene. The same mutants did show, however, a delayed derepression while a
      mutation leading to increased E2F binding resulted in premature up-regulation.
      These findings clearly suggest that E2F contributes to the correct timing of
      cyclin A transcription, presumably by acting as an anti-repressor. In agreement
      with this conclusion, we find that the cyclin A promoter only poorly interacts
      with E2F-4, which is the major E2F family member in G0 cells, while a clear
      binding is seen with E2F-1 and -3, which are up-regulated in late G1.

PMID- 9662328
TI  - p53 deficiency and misexpression of protein kinase CK2alpha collaborate in the
      development of thymic lymphomas in mice.
AB  - Protein kinase CK2 (casein kinase II) is a serine-threonine protein kinase with
      many substrates, some of which are involved in cell cycle regulation. CK2
      activity is elevated in human solid tumors and leukemia, and dysregulated
      expression of CK2 induces lymphoma in transgenic mice. Mice that are deficient in
      p53 also develop lymphomas, and p53 activity may be regulated by CK2
      phosphorylation. Here we demonstrate that CK2alpha transgenic mice partially or
      completely deficient in p53 develop thymic lymphomas at a markedly accelerated
      rate when compared to p53-deficient mice lacking the transgene. Lymphomas
      originating from CK2alpha transgenic mice that are heterozygous for p53 generally
      lose the wild type p53 allele, indicating that loss of p53 is an important step
      in tumor progression. Moreover, though lymphomas occur as early as 3 weeks of age
      in the transgenic mice that are nullizygous for p53, they are still monoclonal,
      indicating that additional stochastic mutations are required for their
      development. These lymphomas express high levels of myc mRNA and frequently
      ectopically express Lmo-2, a transcription factor involved in human T cell acute
      lymphocytic leukemia. The p53-null CK2alpha transgenic lymphomas grow rapidly but
      are highly prone to apoptosis, suggesting that transformation occurs through
      synergistic dysregulation of cell cycle control induced by misexpression of CK2
      and loss of function of p53.

PMID- 9662329
TI  - Mapping of polyomavirus middle T domain that is responsible for AP-1 activation.
AB  - Cell transformation by Polyomavirus middle T (MT) oncoprotein involves binding
      and activation of several cytoplasmic proteins that participate in growth factors
      induced mitogenic signal transduction to the nucleus. We have previously reported
      that the AP-1 transcriptional complex is a target for MT during cell
      transformation. To analyse the interactions between MT and cellular proteins that
      are required for constitutive AP-1 activation, we compared wild type and
      transformation-defective MT mutant cell lines. High AP-1 activity, assessed by
      gel mobility shift assays, displayed by MT-overexpressing cells, is dependent on
      MT binding to phosphatidylinositol-3 kinase (P13K). Treatment with wortmannin (a
      specific P13K inhibitor) leads to decreased AP-1 activity. Supershift and Western
      blot analysis with specific antisera, indicate that JunB and cJun, but not cFos
      or FosB are present in the AP-1 complex. The results confirm the AP-1 complex as
      a downstream MT target and indicate that AP-1 activation may not be sufficient
      for cell transformation, since two transformation-defective MT mutants (250phe
      and MT322) display high AP-1 activity.

PMID- 9662330
TI  - Localization of chromosome 8p regions involved in early tumorigenesis of oral and
      laryngeal squamous carcinoma.
AB  - We analysed 30 primary invasive oral and laryngeal squamous carcinomas (SC), with
      concurrent dysplastic lesions, for genetic alterations at 15 microsatellite loci
      on the short arm of chromosome 8. Overall, loss of heterozygosity (LOH) was
      observed, in at least one informative locus, in 27% of the dysplastic lesions and
      in 67% of the invasive carcinomas. The highest frequency of allele losses in
      dysplasia (20% and 17%), and invasive carcinoma (40% and 48%) were detected in
      the same D8S298 and LPL-tet loci located on chromosomes 8p21 and 8p22
      respectively. The minimal region with LOH was limited to 4.6 megaBases (mBs) at
      8p22 and 7.1 mBs at 8p21. In addition, allelic losses in both dysplastic and
      corresponding invasive specimens were noted at the same loci in some tumors
      suggesting their emergence from a common preneoplastic clone. Allele losses
      correlated significantly with male gender, oral and laryngeal sites and high
      proliferative index. The data suggest that inactivation of tumor suppressor
      gene(s), within these loci, may constitute an early event in the evolution of
      oral and laryngeal SC.

PMID- 9662331
TI  - Spi-1 transgenic mice develop a clonal erythroleukemia which does not depend on
      p53 mutation.
AB  - Spi-1 transcriptional activation and wild-type p53 extinction are two oncogenic
      alterations involved in the malignant transformation of erythroblasts during the
      Friend acute erythroleukemia. To dissect the contribution of these alterations in
      the deregulation of the differentiation and proliferation of erythroblasts, we
      generated spi-1 transgenic mice. Analysis of these animals revealed that Spi-1
      overexpression was directly involved in the block of proerythroblast
      differentiation. However, the erythroleukemia that develops in these animals
      evolved in two steps. During the early step (HS1 step), non tumorigenic
      proerythroblasts remained strictly dependent upon erythropoietin (Epo) for their
      survival and proliferation. Later on, Epo-independent and tumorigenic
      proerythroblasts emerged (HS2 step) suggesting that other oncogenes cooperate
      with Spi-1 to lead to a fully malignant phenotype. By provirus tagging, we
      demonstrate that the HS1 step was clonal indicating that a cell selection must
      occur in vivo. Analysis of the nature of p53 in both the in vivo HS1 and HS2
      proerythroblasts and in cultured erythroblastic cell lines showed that--p53 was
      normal in the HS1 primary tissues but was mutated in the HS1 cultured cell lines-
      p53 was frequently altered in HS2 primary tissues but was found normal in some
      mice. These data indicate that (i) the blockage of the erythroblast
      differentiation by Spi-1 occurs independently of p53 alteration (ii) p53
      alteration is not necessary to confer Epo independence and tumorigenicity to spi
      1 transgenic proerythroblasts.

PMID- 9662332
TI  - GAC1, a new member of the leucine-rich repeat superfamily on chromosome band
      1q32.1, is amplified and overexpressed in malignant gliomas.
AB  - We have used two-dimensional electrophoresis of enzyme-digested genomic DNA to
      identify a novel gene GAC1, which maps at 1q32.1 and which is overexpressed in
      malignant gliomas in which it is amplified. GAC1 encodes a protein which belongs
      to the leucine-rich repeat superfamily. Amplification and overexpression of GAC1
      was demonstrated in two of eight tumors where amplifications were previously
      evidenced by comparative genomic hybridization (one glioblastoma multiforme and
      one anaplastic astrocytoma), and in one of eight unselected glioblastomas
      multiforme. GAC1 exhibits sequence homology with other proteins which function as
      cell-adhesion molecules or as signal transduction receptor and is a likely
      candidate for the target gene in the 1q32.1 amplicon in malignant gliomas.

PMID- 9662333
TI  - Absence of p53-dependent cell cycle regulation in pluripotent mouse cell lines.
AB  - We examined the expression of p53 in three lines of pluripotent embryonal
      carcinoma (EC) and ES cells. p53 mRNA and protein levels were constitutively high
      in two lines but absent from one. In the P19 line of EC cells neither p53 protein
      nor mRNA was detected. The first intron of the p53 gene in these cells had been
      invaded by a murine leukemia virus and there was extensive hypermethylation of
      the p53 gene accompanying its inactivation. In all three cell lines, irradiation
      resulted in arrest of the cells in the G2 but not in the G1 phase of the cell
      cycle despite the induction of p21cip1 in the cell lines expressing p53. Thus,
      the chromosomal stability of EC and ES cells appears to be not dependent on the
      p53 protein and we interpret our results to suggest that these cells may require
      the deletion of p53 dependent cell cycle regulation in order to become
      immortalized.

PMID- 9662334
TI  - Transcriptional regulation of the c-H-ras1 gene by the P53 protein is implicated
      in the development of human endometrial and ovarian tumours.
AB  - The human c-H-ras1 gene contains within the first intron a p53 element, which
      functions as a transcriptional enhancer. Using nuclear extracts from human
      endometrial and ovarian tumours in gel retardation assays, we examined the
      binding levels of the P53 protein to the H-ras element in tumour versus the
      adjacent normal tissue. Elevated P53 binding in the tumour tissue was found in
      5/12 (42%) endometrial and in 2/5 (40%) ovarian specimens and these cases were
      found to overexpress wild-type P53. Loss of P53 binding to the H-ras element due
      to p53 mutations, was observed in 3/12 (25%) endometrial and in 1/5 (20%) ovarian
      cases. Similar P53 binding levels to the H-ras element were found in 4/12 (33%)
      endometrial and in 2/5 (40%) ovarian pairs showing normal expression of wild-type
      P53. Overexpression of the Ras p21 protein correlated with elevated binding and
      increased nuclear levels of wild-type P53. Our results suggest that P53 protein
      alterations, participate in the development of human gynecological neoplasias
      through aberrant transcriptional regulation of the H-ras proto-oncogene.

PMID- 9662335
TI  - Lysophosphatidic acid-induced association of SHP-2 with SHPS-1: roles of RHO,
      FAK, and a SRC family kinase.
AB  - SHPS-1 is an approximately 120 kDa glycosylated receptor like protein that
      contains three immunoglobulin-like domains in its extracellular region as well as
      four potential tyrosine phosphorylation and SRC homology 2 (SH2) domain binding
      sites in its cytoplasmic region. Lysophosphatidic acid (LPA) stimulated the rapid
      tyrosine phosphorylation of SHPS-1 and its subsequent association with SHP-2, a
      protein tyrosine phosphatase containing SH2 domains in Rat-1 fibroblasts. LAP
      induced tyrosine phosphorylation of SHPS-1 was inhibited by Clostridium botulinum
      C3 exoenzyme (which inactivates RHO) but not by pertussis toxin. The protein
      kinase C activator phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA) also
      stimulated tyrosine phosphorylation of SHPS-1; however, down-regulation of
      protein kinase C by prolonged exposure of cells to TPA did not affect LAP-induced
      tyrosine phosphorylation of SHPS-1. LPA-induced tyrosine phosphorylation of SHPS
      1 was markedly reduced in either focal adhesion kinase (FAK)-deficient mouse
      cells or CHO cells overexpressing the tyrosine kinase CSK. Overexpression of a
      catalytically inactivate SHP-2 markedly inhibited MAP kinase activation in
      response to low concentrations of LPA in CHO cells, whereas overexpression of a
      wild-type SHPS-1 did enhance this effect of LPA. Furthermore, MAP kinase
      activation in response to a low concentration of LPA was inhibited by botulinum
      C3 exoenzyme. These results indicate that LPA-induced tyrosine phosphorylation of
      SHPS-1 and its association with SHP-2 may be mediated by a RHO-dependent pathway
      that includes FAK and a SRC family kinase. Thus, in addition to its role in
      receptor tyrosine kinase-mediated MAP kinase activation, the formation of a
      complex between SHPS-1 and SHP-2 may, in part, play an important role in the
      activation of MAP kinase in response to low concentrations of LPA.

PMID- 9662336
TI  - Proteolytic activation of MST/Krs, STE20-related protein kinase, by caspase
      during apoptosis.
AB  - The Fas system has been extensively investigated as a model of apoptosis and the
      caspase cascade has been shown to be a characteristic mechanism of signaling of
      apoptosis. We have identified and purified a kinase that was activated after the
      stimulation of Fas on human thymoma-derived HPB-ALL cells. Partial amino acid
      sequencing of the purified kinase revealed it to be MST/Krs, member of the yeast
      STE20 family of protein kinases. MST/Krs was activated by proteolytic cleavage
      and proteolytic activation was blocked by the caspase inhibitor, Z-VAD-FK. A
      mutant MST with Asp-->Asn replacement at a putative caspase cleavage site was
      resistant to either the proteolytic cleavage or the activation of the kinase
      activity. These findings suggest that proteolytic activation is one activation
      mechanism of MST and plays a role in apoptosis.

PMID- 9662337
TI  - Suppression of c-Fos gene transcription with malignant transformation of human
      bronchial epithelial cells.
AB  - The Activator Protein-1 (AP-1) complex is a dimeric transcription factor composed
      of fos and jun proteins that regulates cellular growth and differentiation. We
      previously demonstrated a reduction in basal AP-1 transcriptional activity
      associated with the malignant transformation of human bronchial epithelial (HBE)
      cells that was, in part, a consequence of decreased c-fos expression. In this
      study, we investigated the mechanisms underlying the reduction in c-fos
      expression associated with the malignant transformation of HBE cells. c-Fos gene
      transcription was lower in tumorigenic HBE cells than in normal HBE cells, and
      the reduction in transcription involved c-fos gene promoter elements from -327 to
      +40. DNaseI footprinting and band shift analyses of motifs within this c-fos
      promoter region, including a cyclic AMP response element (CRE), serum response
      element (SRE), sis-inducible element (SIE), and a YY1 site, revealed that binding
      to these motifs was greater in tumorigenic HBE cells than in normal HBE cells.
      Site-directed mutagenesis of the CRE partially relieved the repression of c-fos
      promoter activity in tumorigenic HBE cells. Further, the activity of the Jun N
      terminal Kinase (JNK)-dependent pathway, which was a positive regulator of the c
      fos promoter, was greater in normal HBE cells than in tumorigenic HBE cells.
      These findings demonstrate a transcriptionally-mediated suppression of c-fos gene
      expression associated with the malignant transformation of HBE cells. The
      decreased activity of the c-fos promoter in tumorigenic 1170I cells appeared to
      involve suppression through a CRE site and reduced activation by JNK-dependent
      pathways.

PMID- 9662338
TI  - Signalling by the oncogenic receptor tyrosine kinase Xmrk leads to activation of
      STAT5 in Xiphophorus melanoma.
AB  - Overexpression of the mutationally activated Xmrk receptor initiates the
      formation of hereditary malignant melanoma in the fish Xiphophorus. In addition
      to transcriptional overexpression a cell-type specific signal transduction is
      essential for Xmrk mediated tumor formation. To elucidate the consequence of Xmrk
      signalling and to identify target proteins that characterize the tumor phenotype,
      we analysed proteins that are strongly tyrosine phosphorylated in the fish
      melanoma cell line PSM. One of the most prominent phosphotyrosine proteins was
      found to be the signal transducer and activator of transcription STAT5. In a
      heterologous cell system (murine pro B-cells), activation of the Xmrk kinase in a
      chimeric receptor induced tyrosine phosphorylation, nuclear translocation and DNA
      binding of STAT5. Following receptor stimulation, expression of the STAT5
      specific target genes cis, osm and pim-1 was induced. In Xiphophorus PSM cells
      STAT5 was found to be preferentially localized in the nucleus, but treatment with
      tyrphostin AG555, a specific Xmrk kinase-inhibitor, blocked nuclear localization.
      In these cells as well as in Xiphophorus melanoma expression of pim-1 and
      constitutive DNA-binding activity of STAT5 was detectable. This constitutive
      activity was higher in malignant than in benign melanomas, indicating that STAT5
      activation is correlated with the malignancy of these tumors.

PMID- 9662339
TI  - Transition from SCLC to NSCLC phenotype is accompanied by an increased TRE
      binding activity and recruitment of specific AP-1 proteins.
AB  - Transitions from small cell (SCLC) to non-small cell lung cancer (NSCLC) cells
      have been documented both in vitro and in vivo and are thought to be an important
      step during tumor progression of human small cell lung cancer towards a treatment
      resistant tumor state. We have screened NSCLC and SCLC cell lines for differences
      in the composition of nuclear transcription factors using consensus
      oligonucleotide sequences (SRE, Ets, TRE, CRE, B-motif, GAS, E-box). We found
      NSCLC cells to exhibit significantly higher AP-1 binding activity than SCLC cells
      consistent with the increased expression of CD44, an AP-1 target gene. To gain
      more insight into the molecular mechanisms underlying these differences, we
      analysed SCLC cell lines (NCI-N592 and NCI-H69) which were phenotypically
      transformed into NSCLC-type cells by transfection with activated H-ras and c-myc
      oncogenes. In these cells, ras-induced transition is accompanied by a strong
      induction of AP-1-binding activity along with increased expression of CD44 mRNA
      and protein. When analysing the composition of the AP-1 complex in more detail
      and comparing ras-induced versus phorbol ester-induced changes, we found Fra-1 to
      be the major component induced in ras-transfected but not in phorbol-ester
      treated or non-treated parental SCLC cells. This finding is paralleled by the
      observation that among the various members of the Fos and Jun family analysed (c
      Fos, FosB, Fra-1, Fra-2, c-Jun, JunD, JunB) fra-1 is the only gene to be
      exclusively expressed in NSCLC cells but not in cells of SCLC origin. Our data,
      thus, point to a histiotype-related mechanism of recruitment among AP-1 proteins
      which may have bearings on the fate of lung cancer development.

PMID- 9662340
TI  - BRCA1 as a potential human prostate tumor suppressor: modulation of
      proliferation, damage responses and expression of cell regulatory proteins.
AB  - In addition to breast and ovarian cancer in women, recent evidence suggests that
      germ-line mutations of the breast cancer susceptibility gene-1 (BRCA1) also
      confer an increased life-time risk for prostate cancer in male probands. However,
      it is not known if and how BRCA1 functions in prostate cancer. We stably
      expressed wild-type (wt) and tumor-associated mutant BRCA1 transgenes in DU-145,
      a human prostate cancer cell line with low endogenous expression of BRCA1. As
      compared with parental cells and vector transfected clones, wtBRCA1 clones
      exhibited: (1) a slightly decreased proliferation rate (doubling time = 25 h as
      compared with 22 h for control cells); (2) a (3-6)-fold increase in sensitivity
      to chemotherapy drugs (adriamycin, camptothecin, and taxol); (3) increased
      susceptibility to drug-induced apoptosis; (4) reduced repair of single-strand DNA
      strand breaks; and (5) alterations in expression of key cellular regulatory
      proteins (including BRCA2, p300, Mdm-2, p21(WAF1/CIP1), Bcl-2 and Bax). Clones
      transfected with the 5677insA breast cancer-associated mutant BRCA1 (insBRCA1)
      displayed a similar phenotype to wtBRCA1 clones, except that insBRCA1 clones had
      a significantly decreased proliferation rate (doubling time = 42 h). On the other
      hand, cells transfected with with 185delAG mutant BRCA1 showed no obvious
      phenotype as compared with parental or vector transfected cells. These findings
      suggest that BRCA1 may function as a human prostate tumor suppressor by virtue of
      its ability to modulate proliferation and various components of the cellular
      damage response. They also suggest several potential target gene products for a
      BRCA1 prostate tumor suppressor function.

PMID- 9662341
TI  - Mutations in OGG1, a gene involved in the repair of oxidative DNA damage, are
      found in human lung and kidney tumours.
AB  - The human OGG1 gene encodes a DNA glycosylase activity catalysing the excision of
      the mutagenic lesion 7,8-dihydro-8-oxoguanine from oxidatively damaged DNA. The
      OGG1 gene was localized to chromosome 3p25, a region showing frequent loss of
      heterozygosity (LOH) in lung and kidney tumours. In this study, we have analysed
      by RT-PCR the expression of OGG1 in 25 small cell lung cancers, in 15 kidney
      carcinomas and the 15 normal kidney counterparts. The results show that OGG1
      messenger RNA can be detected in all tumours tested and that no significant
      difference was observed in the level of expression between normal and tumoral
      kidney tissues. Denaturing gradient gel electrophoresis (DGGE) was used to screen
      this series of human tumours for alterations in the OGG1 cDNA. The study revealed
      homozygous mutations in three tumours, two from lung and one from kidney.
      Sequencing analysis of the mutants identified a single base substitution in each
      of the three cases: two transversions (GC to TA and TA to AT) and one transition
      (GC to AT). All three substitutions cause an amino acid change in the hOgg1
      protein. For the mutant kidney tumour, the normal tissue counterpart shows a wild
      type profile. These results suggest a role for OGG1 mutations in the course of
      the multistage process of carcinogenesis in lung or kidney.

PMID- 9662342
TI  - Amyloid and Alzheimer disease.

PMID- 9662343
TI  - Vaccine reactions.

PMID- 9662344
TI  - Vaccine reactions.

PMID- 9662345
TI  - Vaccine reactions.

PMID- 9662346
TI  - A new human p53 homologue.

PMID- 9662347
TI  - Anti-KS activity still a mystery.

PMID- 9662348
TI  - Government report highlights the lack of clinical trial protection in the US.

PMID- 9662349
TI  - World Bank will lend more money to India for AIDS.

PMID- 9662350
TI  - Italy moves towards a 'scientific parliament'.

PMID- 9662351
TI  - British MRC reprimanded over clinical test record.

PMID- 9662352
TI  - NIH increase efforts to tackle obesity.

PMID- 9662353
TI  - HIV vaccines--and the winner is...

PMID- 9662354
TI  - Canada to specialize in aging research.

PMID- 9662355
TI  - Alpha synuclein in neurodegenerative disorders: murderer or accomplice?

PMID- 9662356
TI  - Genetic testing and Alzheimer disease: has the time come? Alzheimer Disease
      Working Group of the Stanford Program in Genomics, Ethics & Society.

PMID- 9662357
TI  - Breast cancer biology blossoms in the clinic.

PMID- 9662358
TI  - International health beyond 2000.

PMID- 9662359
TI  - The gammadelta T-cell bridge: linking innate and acquired immunity.

PMID- 9662360
TI  - Keeping up with the Cajal rhythm.

PMID- 9662361
TI  - Full speed ahead for tumor screening.

PMID- 9662362
TI  - Brain injury and immunosuppression.

PMID- 9662363
TI  - The viral triggering of autoimmune disease.

PMID- 9662364
TI  - All in the p53 family.

PMID- 9662365
TI  - Amyloid beta threads in the fabric of Alzheimer's disease.

PMID- 9662366
TI  - Cyclooxygenase-2: the future is now.

PMID- 9662367
TI  - T lymphocytes with a normal ADA gene accumulate after transplantation of
      transduced autologous umbilical cord blood CD34+ cells in ADA-deficient SCID
      neonates.
AB  - Adenosine deaminase-deficient severe combined immunodeficiency was the first
      disease investigated for gene therapy because of a postulated production or
      survival advantage for gene-corrected T lymphocytes, which may overcome
      inefficient gene transfer. Four years after three newborns with this disease were
      given infusions of transduced autologous umbilical cord blood CD34+ cells, the
      frequency of gene-containing T lymphocytes has risen to 1-10%, whereas the
      frequencies of other hematopoietic and lymphoid cells containing the gene remain
      at 0.01-0.1%. Cessation of polyethylene glycol-conjugated adenosine deaminase
      enzyme replacement in one subject led to a decline in immune function, despite
      the persistence of gene-containing T lymphocytes. Thus, despite the long-term
      engraftment of transduced stem cells and selective accumulation of gene
      containing T lymphocytes, improved gene transfer and expression will be needed to
      attain a therapeutic effect.

PMID- 9662368
TI  - Diabetes induced by Coxsackie virus: initiation by bystander damage and not
      molecular mimicry.
AB  - Viral induction of autoimmunity is thought to occur by either bystander T-cell
      activation or molecular mimicry. Coxsackie B4 virus is strongly associated with
      the development of insulin-dependent diabetes mellitus in humans and shares
      sequence similarity with the islet autoantigen glutamic acid decarboxylase. We
      infected different strains of mice with Coxsackie B4 virus to discriminate
      between the two possible induction mechanisms, and found that mice with
      susceptible MHC alleles had no viral acceleration of diabetes, but mice with a T
      cell receptor transgene specific for a different islet autoantigen rapidly
      developed diabetes. These results show that diabetes induced by Coxsackie virus
      infection is a direct result of local infection leading to inflammation, tissue
      damage, and the release of sequestered islet antigen resulting in the re
      stimulation of resting autoreactive T cells, further indicating that the islet
      antigen sensitization is an indirect consequence of the viral infection.

PMID- 9662369
TI  - Genealogy of the CCR5 locus and chemokine system gene variants associated with
      altered rates of HIV-1 disease progression.
AB  - Allelic variants for the HIV-1 co-receptors chemokine receptor 5 (CCR5) and CCR2,
      as well as the ligand for the co-receptor CXCR4, stromal-derived factor (SDF-1),
      have been associated with a delay in disease progression. We began this study to
      test whether polymorphisms in the CCR5 regulatory regions influence the course of
      HIV-1 disease, as well as to examine the role of the previously identified
      allelic variants in 1,090 HIV-1 infected individuals. Here we describe the
      evolutionary relationships between the phenotypically important CCR5 alleles,
      define precisely the CCR5 regulatory sequences that are linked to the CCR5
      delta32 and CCR2-641 polymorphisms, and identify genotypes associated with
      altered rates of HIV-1 disease progression. The disease-retarding effects of the
      CCR2-641 allele were found in African Americans but not in Caucasians, and the
      SDF1-3'A/3'A genotype was associated with an accelerated progression to death. In
      contrast, the CCR5-delta32 allele and a CCR5 promoter mutation with which it is
      tightly linked were associated with limited disease-retarding effects.
      Collectively, these findings draw attention to a complex array of genetic
      determinants in the HIV-host interplay.

PMID- 9662370
TI  - Limited CD4+ T-cell renewal in early HIV-1 infection: effect of highly active
      antiretroviral therapy.
AB  - We show that the fraction of proliferating CD4+ lymphocytes is similar in HIV
      infected subjects in the early stage of disease and in HIV-negative subjects,
      whereas the fraction of proliferating CD8+ lymphocytes is increased 6.8-fold in
      HIV-infected subjects. After initiation of antiviral therapy, there is a late
      increase in proliferating CD4+ T cells associated with the restoration of CD4+ T
      cell counts. These results provide strong support for the idea of limited CD4+ T
      cell renewal in the early stage of HIV infection and indicate that after
      effective suppression of virus replication, the mechanisms of CD4+ T-cell
      production are still functional in early HIV infection.

PMID- 9662371
TI  - Transforming growth factor-beta1 is a new form of tumor suppressor with true
      haploid insufficiency.
AB  - Components of the transforming growth factor-beta (TGF-beta) signal pathway
      function as classic tumor suppressors, but the role of the TGF-betas themselves
      is less clear. Here we show that mice heterozygous for deletion of the TGF-beta1
      gene express only 10-30% of wild-type TGF-beta1 protein levels. Although grossly
      normal, these mice have a subtly altered proliferative phenotype, with increased
      cell turnover in the liver and lung. Treatment of these mice with chemical
      carcinogens resulted in enhanced tumorigenesis when compared with wild-type
      littermates. However, tumors in the heterozygous mice did not lose the remaining
      wild-type TGF-beta1 allele, indicating that the TGF-beta1 ligand is a new form of
      tumor suppressor that shows true haploid insufficiency in its ability to protect
      against tumorigenesis.

PMID- 9662372
TI  - Sympathetic activation triggers systemic interleukin-10 release in
      immunodepression induced by brain injury.
AB  - The mechanism of immunodepression after brain injury is not yet clear. Here we
      demonstrate rapid systemic release of the immunoinhibitory cytokine interleukin
      10, monocytic deactivation and a high incidence of infection in patients with
      'sympathetic storm' due to acute accidental or iatrogenic brain trauma. In vitro
      studies showed that within minutes catecholamines trigger the secretion of
      interleukin-10 from unstimulated monocytes through a beta-adrenoreceptor
      mediated, cAMP/protein kinase A-dependent pathway. We found that in a rat model
      of acute brain injury, the beta-receptor antagonist propranolol prevented the
      increase of interleukin-10 plasma levels. Rapid monocytic interleukin-10 release
      after sympathetic activation may represent a common pathway for immunodepression
      induced by stress and injury.

PMID- 9662373
TI  - Implantation of stimulated homologous macrophages results in partial recovery of
      paraplegic rats.
AB  - Postinjury recovery in most tissues requires an effective dialog with
      macrophages; however, in the mammalian central nervous system, this dialog may be
      restricted (possibly due to its immune-privileged status), which probably
      contributes to its regeneration failure. We circumvented this by implanting
      macrophages, pre-exposed ex vivo to peripheral nerve segments, into transected
      rat spinal cord. This stimulated tissue repair and partial recovery of motor
      function, manifested behaviorally by movement of hind limbs, plantar placement of
      the paws and weight support, and electrophysiologically by cortically evoked hind
      limb muscle response. We substantiated these findings immunohistochemically by
      demonstrating continuity of labeled nerve fibers across the transected site, and
      by tracing descending fibers distally to it by anterograde labeling. In recovered
      rats, retransection of the cord above the primary transection site led to loss of
      recovery, indicating the involvement of long descending spinal tracts. Injection
      of macrophages into the site of injury is relatively non-invasive and, as the
      cells are autologous, it may be developed into a clinical therapy.

PMID- 9662374
TI  - Beta-sheet breaker peptides inhibit fibrillogenesis in a rat brain model of
      amyloidosis: implications for Alzheimer's therapy.
AB  - Inhibition of cerebral amyloid beta-protein deposition seems to be an important
      target for Alzheimer's disease therapy. Amyloidogenesis could be inhibited by
      short synthetic peptides designed as beta-sheet breakers. Here we demonstrate a 5
      residue peptide that inhibits amyloid beta-protein fibrillogenesis, disassembles
      preformed fibrils in vitro and prevents neuronal death induced by fibrils in cell
      culture. In addition, the beta-sheet breaker peptide significantly reduces
      amyloid beta-protein deposition in vivo and completely blocks the formation of
      amyloid fibrils in a rat brain model of amyloidosis. These findings may provide
      the basis for a new therapeutic approach to prevent amyloidosis in Alzheimer's
      disease.

PMID- 9662375
TI  - Aging renders the brain vulnerable to amyloid beta-protein neurotoxicity.
AB  - The formation of fibrillar deposits of amyloid beta protein (Abeta) in the brain
      is a pathological hallmark of Alzheimer's disease (AD). A central question is
      whether Abeta plays a direct role in the neurodegenerative process in AD. The
      involvement of Abeta in the neurodegenerative process is suggested by the
      neurotoxicity of the fibrillar form of Abeta in vitro. However, mice transgenic
      for the Abeta precursor protein that develop amyloid deposits in the brain do not
      show the degree of neuronal loss or tau phosphorylation found in AD. Here we show
      that microinjection of plaque-equivalent concentrations of fibrillar, but not
      soluble, Abeta in the aged rhesus monkey cerebral cortex results in profound
      neuronal loss, tau phosphorylation and microglial proliferation. Fibrillar Abeta
      at plaque-equivalent concentrations is not toxic in the young adult rhesus brain.
      Abeta toxicity in vivo is also highly species-specific; toxicity is greater in
      aged rhesus monkeys than in aged marmoset monkeys, and is not significant in aged
      rats. These results suggest that Abeta neurotoxicity in vivo is a pathological
      response of the aging brain, which is most pronounced in higher order primates.
      Thus, longevity may contribute to the unique susceptibility of humans to
      Alzheimer's disease by rendering the brain vulnerable to Abeta neurotoxicity.

PMID- 9662376
TI  - Detection of single amyloid beta-protein aggregates in the cerebrospinal fluid of
      Alzheimer's patients by fluorescence correlation spectroscopy.
AB  - Alzheimer's disease is associated with the intraparenchymal growth of plaque-like
      amyloid deposits. Amyloid plaques are formed by the progressive deposition and
      transformation of soluble amyloid beta-protein monomers into insoluble and
      fibrillar aggregates that contain amyloid beta-protein in a beta-pleated sheet
      conformation. This process is described as 'seeded polymerization' of the
      monomers with slow-nucleation and fast-growth kinetics. Soluble amyloid beta
      protein monomers are present in the cortical extracellular space and in the
      cerebrospinal fluid, whereas insoluble aggregates so far can be found only by the
      examination of brain tissue by biopsy or autopsy. Here we present a biophysical
      method that uses the principle of seeded polymerization in combination with
      fluorescence correlation spectroscopy, which allowed us to detect single amyloid
      beta-peptide aggregates in the cerebrospinal fluid samples from Alzheimer's
      patients. All of 15 Alzheimer's samples but none of the 19 age-matched control
      samples produced large peaks with fluorescence correlation spectroscopy
      indicating the rapid aggregation of the fluorescent labelled synthetic amyloid
      beta-protein probe onto the amyloid beta-protein 'seeds' present in the
      cerebrospinal fluid. Our method could enable easy in vivo detection of the
      cerebral amyloid beta-protein pathology of Alzheimer's disease and might be of
      potential value to facilitate its routine diagnosis.

PMID- 9662377
TI  - Inhibition of presenilin 1 expression is promoted by p53 and p21WAF-1 and results
      in apoptosis and tumor suppression.
AB  - Previously, we cloned a cDNA fragment, TSIP 2 (tumor suppressor inhibited pathway
      clone 2), that detects by northern blot analysis of M1-LTR6 cells a 3-kb mRNA
      downregulated during p53-induced apoptosis. Cloning the full-length TSIP 2 cDNA
      showed that it corresponds to the presenilin 1 (PS1) gene, in which mutations
      have been reported in early-onset familial Alzheimer's disease. Here we
      demonstrate that PS1 is downregulated in a series of model systems for p53
      dependent and p53-independent apoptosis and tumor suppression. To investigate the
      biological relevance of this downregulation, we stably transfected U937 cells
      with antisense PS1 cDNA. The downregulation of PS1 in these U937 transfectants
      results in reduced growth with an increased fraction of the cells in apoptosis.
      When injected into mice homozygous for severe combined immunodeficiency disease
      (scid/scid mice), these cells show a suppression of their malignant phenotype.
      Our results indicate that PS1, initially identified in a neurodegenerative
      disease, may also be involved in the regulation of cancer-related pathways.

PMID- 9662378
TI  - Cloning and functional analysis of human p51, which structurally and functionally
      resembles p53.
AB  - The p53 tumor suppressor gene, which is induced by DNA damage and/or stress
      stimuli, causes cells to undergo G1-arrest or apoptotic death; thus it plays an
      essential role in human carcinogenesis. We have searched for p53-related genes by
      using degenerate PCR, and have identified two cDNA fragments similar to but
      distinct from p53: one previously reported, p73, and the other new. We cloned two
      major splicing variants of the latter gene and named these p51A and p51B (a human
      homologue of rat Ket). The p51A gene encodes a 448-amino-acid protein with a
      molecular weight of 50.9 kDa; and p51B, a 641-amino-acid protein with a molecular
      weight of 71.9 kDa. In contrast with the ubiquitous expression of p53, expression
      of p51 mRNA was found in a limited number of tissues, including skeletal muscle,
      placenta, mammary gland, prostate, trachea, thymus, salivary gland, uterus, heart
      and lung. In p53-deficient cells, p51A induced growth-suppression and apoptosis,
      and upregulated p21waf-1 through p53 regulatory elements. Mutations in p51 were
      found in some human epidermal tumors.

PMID- 9662379
TI  - Tissue microarrays for high-throughput molecular profiling of tumor specimens.
AB  - Many genes and signalling pathways controlling cell proliferation, death and
      differentiation, as well as genomic integrity, are involved in cancer
      development. New techniques, such as serial analysis of gene expression and cDNA
      microarrays, have enabled measurement of the expression of thousands of genes in
      a single experiment, revealing many new, potentially important cancer genes.
      These genome screening tools can comprehensively survey one tumor at a time;
      however, analysis of hundreds of specimens from patients in different stages of
      disease is needed to establish the diagnostic, prognostic and therapeutic
      importance of each of the emerging cancer gene candidates. Here we have developed
      an array-based high-throughput technique that facilitates gene expression and
      copy number surveys of very large numbers of tumors. As many as 1000 cylindrical
      tissue biopsies from individual tumors can be distributed in a single tumor
      tissue microarray. Sections of the microarray provide targets for parallel in
      situ detection of DNA, RNA and protein targets in each specimen on the array, and
      consecutive sections allow the rapid analysis of hundreds of molecular markers in
      the same set of specimens. Our detection of six gene amplifications as well as
      p53 and estrogen receptor expression in breast cancer demonstrates the power of
      this technique for defining new subgroups of tumors.

PMID- 9662380
TI  - Interstitial cells of Cajal generate a rhythmic pacemaker current.
AB  - Networks of interstitial cells of Cajal embedded in the musculature of the
      gastrointestinal tract are involved in the generation of electrical pacemaker
      activity for gastrointestinal motility. This pacemaker activity manifests itself
      as rhythmic slow waves in membrane potential, and controls the frequency and
      propagation characteristics of gut contractile activity. Mice that lack a
      functional Kit receptor fail to develop the network of interstitial cells of
      Cajal associated with Auerbach's plexus in the mouse small intestine and do not
      generate slow wave activity. These cells could provide an essential component of
      slow wave activity (for example, a biochemical trigger that would be transferred
      to smooth muscle cells), or provide an actual pacemaker current that could
      initiate slow waves. Here we provide direct evidence that a single cell,
      identified as an interstitial cell of Cajal by light microscopy, electron
      microscopy and expression of Kit mRNA, generates spontaneous contractions and a
      rhythmic inward current that is insensitive to L-type calcium channel blockers.
      Identification of the pacemaker of gut motility will aid in the elucidation of
      the pathophysiology of intestinal motor disorders, and provide a target cell for
      pharmacological treatment.

PMID- 9662381
TI  - Peripheral expansion of pre-existing mature T cells is an important means of CD4+
      T-cell regeneration HIV-infected adults.
AB  - The CD4+ T-cell pool in HIV-infected patients is in a constant state of flux as
      CD4+ T cells are infected and destroyed by HIV and new cells take their place. To
      study T-cell survival, we adoptively transferred peripheral blood lymphocytes
      transduced with the neomycin phosphotransferase gene between syngeneic twin pairs
      discordant for HIV infection. A stable fraction of marked CD4+ T cells persisted
      in the circulation for four to eighteen weeks after transfer in all patients.
      After this time there was a precipitous decline in marked cells in three of the
      patients. At approximately six months, marked cells were in lymphoid tissues in
      proportions comparable to those found in peripheral blood. In two patients, the
      proportion of total signal for the transgene (found by PCR analysis) in the
      CD4/CD45RA+ T-cell population relative to the CD4/CD45RO+ population increased in
      the weeks after cell infusion. These findings indicate that genetically-marked
      CD4+ T cells persist in vivo for weeks to months and that the CD4+ T-cell pool in
      adults is maintained mostly by the division of mature T cells rather than by
      differentiation of prethymic stem cells. Thus, after elements of the T-cell
      repertoire are lost through HIV infection, they may be difficult to replace.

PMID- 9662382
TI  - In vivo cellular optical coherence tomography imaging.

PMID- 9662383
TI  - Privacy matters.

PMID- 9662384
TI  - Weighing in on diabetes risk.

PMID- 9662385
TI  - Counting on Xist.

PMID- 9662386
TI  - Sometimes it's hot, sometimes it's not.

PMID- 9662387
TI  - Nuclear power and mitochondrial disease.

PMID- 9662388
TI  - It's raining SNPs, hallelujah?

PMID- 9662389
TI  - Cloning and characterization of a family of novel mammalian DNA (cytosine-5)
      methyltransferases.

PMID- 9662390
TI  - Non-invasive sexing of preimplantation stage mammalian embryos.

PMID- 9662391
TI  - Human genome annotation--a possible role for HUGO? Human Genome Organisation.

PMID- 9662392
TI  - PTEN and inherited hamartoma-cancer syndromes.

PMID- 9662393
TI  - Mutation detection and single-molecule counting using isothermal rolling-circle
      amplification.
AB  - Rolling-circle amplification (RCA) driven by DNA polymerase can replicate
      circularized oligonucleotide probes with either linear or geometric kinetics
      under isothermal conditions. In the presence of two primers, one hybridizing to
      the + strand, and the other, to the - strand of DNA, a complex pattern of DNA
      strand displacement ensues that generates 10(9) or more copies of each circle in
      90 minutes, enabling detection of point mutations in human genomic DNA. Using a
      single primer, RCA generates hundreds of tandemly linked copies of a covalently
      closed circle in a few minutes. If matrix-associated, the DNA product remains
      bound at the site of synthesis, where it may be tagged, condensed and imaged as a
      point light source. Linear oligonucleotide probes bound covalently on a glass
      surface can generate RCA signals, the colour of which indicates the allele status
      of the target, depending on the outcome of specific, target-directed ligation
      events. As RCA permits millions of individual probe molecules to be counted and
      sorted using colour codes, it is particularly amenable for the analysis of rare
      somatic mutations. RCA also shows promise for the detection of padlock probes
      bound to single-copy genes in cytological preparations.

PMID- 9662394
TI  - DNA sequence diversity in a 9.7-kb region of the human lipoprotein lipase gene.
AB  - Lipoprotein lipase plays a central role in lipid metabolism and the gene that
      encodes this enzyme (LPL) is a candidate susceptibility gene for cardiovascular
      disease. Here we report the complete sequence of a fraction of the LPL gene for
      71 individuals (142 chromosomes) from three populations that may have different
      histories affecting the organization of the sequence variation. Eighty-eight
      sites in this 9.7 kb vary among individuals from these three populations. Of
      these, 79 were single nucleotide substitutions and 9 sites involved insertion
      deletion variations. The average nucleotide diversity across the region was 0.2%
      (or on average 1 variable site every 500 bp). At 34 of these sites, the variation
      was found in only one of the populations, reflecting the differing population and
      mutational histories. If LPL is a typical human gene, the pattern of sequence
      variation that exists in introns as well as exons, even for the small number of
      samples considered here, will present challenges for the identification of sites,
      or combinations of sites, that influence variation in risk of disease in the
      population at large.

PMID- 9662395
TI  - Identification of the gene responsible for Best macular dystrophy.
AB  - Best macular dystrophy (BMD), also known as vitelliform macular dystrophy (VMD2;
      OMIM 153700), is an autosomal dominant form of macular degeneration characterized
      by an abnormal accumulation of lipofuscin within and beneath the retinal pigment
      epithelium cells. In pursuit of the disease gene, we limited the minimum genetic
      region by recombination breakpoint analysis and mapped to this region a novel
      retina-specific gene (VMD2). Genetic mapping data, identification of five
      independent disease-specific mutations and expression studies provide evidence
      that mutations within the candidate gene are a cause of BMD. The 3' UTR of the
      candidate gene contains a region of antisense complementarity to the 3' UTR of
      the ferritin heavy-chain gene (FTH1), indicating the possibility of antisense
      interaction between VMD2 and FTH1 transcripts.

PMID- 9662396
TI  - Role of the region 3' to Xist exon 6 in the counting process of X-chromosome
      inactivation.
AB  - During early embryogenesis of female mammals, one of the two X chromosomes is
      randomly chosen to be inactivated in each cell, leading to the transcriptional
      silencing of thousands of genes on this chromosome. This random X-inactivation
      process also occurs during in vitro differentiation of female embryonic stem (ES)
      cells. A locus on the X chromosome, the X inactivation centre (Xic) is initially
      'counted', given that at least two copies of Xic must be present per diploid
      genome in order for inactivation to occur. The counting process ensures that one
      X chromosome remains active in diploid cells. In the mouse, the essential
      functions of Xic can be assured by a 450-kb region containing the Xist gene. Xist
      maps within Xic (refs 7-10) and is necessary in cis for inactivation. The Xist
      transcript is a 15-kb RNA which is confined within the nucleus and coats the
      inactive X chromosome. In order to characterize functional elements within Xic
      and the Xist gene, we created a 65-kb cre/loxP deletion extending 3' to Xist exon
      6. In undifferentiated ES cells, Xist expression from the deleted X chromosome
      was markedly reduced. In differentiated XX ES cells containing one deleted X
      chromosome, the X inactivation process still occurred but was never initiated
      from the unmutated X chromosome. In differentiated ES cells that were essentially
      XO, the mutated Xic was capable of initiating X inactivation, even in the absence
      of another Xic. These results demonstrate a role for the region 3' to Xist exon 6
      in the counting process and suggest that counting is mediated by a repressive
      mechanism which prevents inactivation of a single X chromosome in diploid cells.

PMID- 9662397
TI  - BRCA1 protein is linked to the RNA polymerase II holoenzyme complex via RNA
      helicase A.
AB  - The breast cancer specific tumour suppressor protein, BRCA1 (refs 1,2), activates
      transcription when linked with a DNA-binding domain and is a component of the RNA
      polymerase II (Pol II) holoenzyme. We show here that RNA helicase A (RHA) protein
      links BRCA1 to the holoenzyme complex. The region of BRCA1 which interacts with
      RHA and, thus, the holoenzyme complex, corresponds to subregions of the BRCT
      domain of BRCA1 (ref. 9). This interaction was shown to occur in yeast nuclei,
      and expression in human cells of a truncated RHA molecule which retains binding
      to BRCA1 inhibited transcriptional activation mediated by the BRCA1 carboxy
      terminus. These data are the first to identify a specific protein interaction
      with the BRCA1 C-terminal domain and are consistent with the model that BRCA1
      functions as a transcriptional coactivator.

PMID- 9662398
TI  - Total colourblindness is caused by mutations in the gene encoding the alpha
      subunit of the cone photoreceptor cGMP-gated cation channel.
AB  - Total colourblindness (OMIM 216900), also referred to as rod monochromacy (RM) or
      complete achromatopsia, is a rare, autosomal recessive inherited and congenital
      disorder characterized by photophobia, reduced visual acuity, nystagmus and the
      complete inability to discriminate between colours. Electroretinographic
      recordings show that in RM, rod photoreceptor function is normal, whereas cone
      photoreceptor responses are absent. The locus for RM has been mapped to
      chromosome 2q11 (ref. 2), however the gene underlying RM has not yet been
      identified. Recently, a suitable candidate gene, CNGA3, encoding the alpha
      subunit of the cone photoreceptor cGMP-gated cation channel, a key component of
      the phototransduction pathway, has been cloned and assigned to human chromosome
      2q11 (refs 3,4). We report the identification of missense mutations in CNGA3 in
      five families with RM. Homozygous mutations are present in two families, whereas
      the remaining families show compound heterozygous mutations. In all cases, the
      segregation pattern of the mutations is consistent with the autosomal recessive
      inheritance of the disease and all mutations affect amino acids that are highly
      conserved among cyclic nucleotide gated channels (CNG) in various species. This
      is the first report of a colour vision disorder caused by defects other than
      mutations in the cone pigment genes, and implies at least in this instance a
      common genetic basis for phototransduction in the three different cone
      photoreceptors of the human retina.

PMID- 9662399
TI  - An L-type calcium-channel gene mutated in incomplete X-linked congenital
      stationary night blindness.
AB  - The locus for the incomplete form of X-linked congenital stationary night
      blindness (CSNB2) maps to a 1.1-Mb region in Xp11.23 between markers DXS722 and
      DXS255. We identified a retina-specific calcium channel alpha1-subunit gene
      (CACNA1F) in this region, consisting of 48 exons encoding 1966 amino acids and
      showing high homology to L-type calcium channel alpha1-subunits. Mutation
      analysis in 13 families with CSNB2 revealed nine different mutations in 10
      families, including three nonsense and one frameshift mutation. These data
      indicate that aberrations in a voltage-gated calcium channel, presumably causing
      a decrease in neurotransmitter release from photoreceptor presynaptic terminals,
      are a frequent cause of CSNB2.

PMID- 9662400
TI  - Loss-of-function mutations in a calcium-channel alpha1-subunit gene in Xp11.23
      cause incomplete X-linked congenital stationary night blindness.
AB  - X-linked congenital stationary night blindness (CSNB) is a recessive non
      progressive retinal disorder characterized by night blindness, decreased visual
      acuity, myopia, nystagmus and strabismus. Two distinct clinical entities of X
      linked CSNB have been proposed. Patients with complete CSNB show moderate to
      severe myopia, undetectable rod function and a normal cone response, whereas
      patients with incomplete CSNB show moderate myopia to hyperopia and subnormal but
      measurable rod and cone function. The electrophysiological and psychophysical
      features of these clinical entities suggest a defect in retinal
      neurotransmission. The apparent clinical heterogeneity in X-linked CSNB reflects
      the recently described genetic heterogeneity in which the locus for complete CSNB
      (CSNB1) was mapped to Xp11.4, and the locus for incomplete CSNB (CSNB2) was
      refined within Xp11.23 (ref. 5). A novel retina-specific gene mapping to the
      CSNB2 minimal region was characterized and found to have similarity to voltage
      gated L-type calcium channel alpha1-subunit genes. Mutation analysis of this new
      alpha1-subunit gene, CACNA1F, in 20 families with incomplete CSNB revealed six
      different mutations that are all predicted to cause premature protein truncation.
      These findings establish that loss-of-function mutations in CACNA1F cause
      incomplete CSNB, making this disorder an example of a human channelopathy of the
      retina.

PMID- 9662401
TI  - Mutations in the glucokinase gene of the fetus result in reduced birth weight.
AB  - Low birth weight and fetal thinness have been associated with non-insulin
      dependent diabetes mellitus (NIDDM) and insulin resistance in childhood and
      adulthood. It has been proposed that this association results from fetal
      programming in response to the intrauterine environment. An alternative
      explanation is that the same genetic influences alter both intrauterine growth
      and adult glucose tolerance. Fetal insulin secretion in response to maternal
      glycaemia plays a key role in fetal growth, and adult insulin secretion is a
      primary determinant of glucose tolerance. We hypothesized that a defect in the
      sensing of glucose by the pancreas, caused by a heterozygous mutation in the
      glucokinase gene, could reduce fetal growth and birth weight in addition to
      causing hyperglycaemia after birth. In 58 offspring, where one parent has a
      glucokinase mutation, the inheritance of a glucokinase mutation by the fetus
      resulted in a mean reduction of birth weight of 533 g (P=0.002). In 19 of 21
      sibpairs discordant for the presence of a glucokinase mutation, the child with
      the mutation had a lower birth weight, with a mean difference of 521 g
      (P=0.0002). Maternal hyperglycaemia due to a glucokinase mutation resulted in a
      mean increase in birth weight of 601 g (P=0.001). The effects of maternal and
      fetal glucokinase mutations on birth weight were additive. We propose that these
      changes in birth weight reflect changes in fetal insulin secretion which are
      influenced directly by the fetal genotype and indirectly, through maternal
      hyperglycaemia, by the maternal genotype. This observation suggests that
      variation in fetal growth could be used in the assessment of the role of genes
      which modify either insulin secretion or insulin action.

PMID- 9662402
TI  - Mutation in Npps in a mouse model of ossification of the posterior longitudinal
      ligament of the spine.
AB  - Ossification of the posterior longitudinal ligament of the spine (OPLL) is a
      common form of human myelopathy caused by a compression of the spinal cord by
      ectopic ossification of spinal ligaments. To elucidate the genetic basis for
      OPLL, we have been studying the ttw (tiptoe walking; previously designated twy)
      mouse, a naturally occurring mutant which exhibits ossification of the spinal
      ligaments very similar to human OPLL (refs 3,4). Using a positional candidate
      gene approach, we determined the ttw phenotype is caused by a nonsense mutation
      (glycine 568 to stop) in the Npps gene which encodes nucleotide pyrophosphatase.
      This enzyme regulates soft-tissue calcification and bone mineralization by
      producing inorganic pyrophosphate, a major inhibitor of calcification. The
      accelerated bone formation characteristic of ttw mice is likely to result from
      dysfunction of NPPS caused by predicted truncation of the gene product, resulting
      in the loss of more than one-third of the native protein. Our results may lead to
      novel insights into the mechanism of ectopic ossification and the aetiology of
      human OPLL.

PMID- 9662403
TI  - The mouse pudgy mutation disrupts Delta homologue Dll3 and initiation of early
      somite boundaries.
AB  - Pudgy (pu) homozygous mice exhibit clear patterning defects at the earliest
      stages of somitogenesis, resulting in adult mice with severe vertebral and rib
      deformities. By positional cloning and complementation, we have determined that
      the pu phenotype is caused by a mutation in the delta-like 3 gene (Dll3), which
      is homologous to the Notch-ligand Delta in Drosophila. Histological and molecular
      marker analyses show that the pu mutation disrupts the proper formation of
      morphological borders in early somite formation and of rostral-caudal compartment
      boundaries within somites. Viability analysis also indicates an important role in
      early development. The results point to a key role for a Notch-signalling pathway
      in the initiation of patterning of vertebrate paraxial mesoderm.

PMID- 9662404
TI  - Mutations in the mineralocorticoid receptor gene cause autosomal dominant
      pseudohypoaldosteronism type I.
AB  - Pseudohypoaldosteronism type I (PHA1) is characterized by neonatal renal salt
      wasting with dehydration, hypotension, hyperkalaemia and metabolic acidosis,
      despite elevated aldosterone levels. Two forms of PHA1 exist. An autosomal
      recessive form features severe disease with manifestations persisting into
      adulthood. This form is caused by loss-of-function mutations in genes encoding
      subunits of the amiloride-sensitive epithelial sodium channel (ENaC; refs 2,3).
      Autosomal dominant or sporadic PHA1 is a milder disease that remits with age.
      Among six dominant and seven sporadic PHA1 kindreds, we have found no ENaC gene
      mutations, implicating mutations in other genes. As ENaC activity in the kidney
      is regulated by the steroid hormone aldosterone acting through the
      mineralocorticoid receptor, we have screened the mineralocorticoid receptor gene
      (MLR) for variants and have identified heterozygous mutations in one sporadic and
      four dominant kindreds. These include two frameshift mutations (one a de novo
      mutation), two premature termination codons and one splice donor mutation. These
      mutations segregate with PHA1 and are not found in unaffected subjects. These
      findings demonstrate that heterozygous MLR mutations cause PHA1, underscore the
      important role of mineralocorticoid receptor function in regulation of salt and
      blood pressure homeostasis in humans and motivate further study of this gene for
      a potential role in blood pressure variation.

PMID- 9662405
TI  - Renal and intestinal absorptive defects in mice lacking the NHE3 Na+/H+
      exchanger.
AB  - NHE3 is one of five plasma membrane Na+/H+ exchangers and is encoded by the mouse
      gene Slc9a3. It is expressed on apical membranes of renal proximal tubule and
      intestinal epithelial cells and is thought to play a major role in NaCl and HCO3-
      absorption. As the distribution of NHE3 overlaps with that of the NHE2 isoform in
      kidney and intestine, the function and relative importance of NHE3 in vivo is
      unclear. To analyse its physiological functions, we generated mice lacking NHE3
      function. Homozygous mutant (Slc9a3-/-) mice survive, but they have slight
      diarrhoea and blood analysis revealed that they are mildly acidotic. HCO3- and
      fluid absorption are sharply reduced in proximal convoluted tubules, blood
      pressure is reduced and there is a severe absorptive defect in the intestine.
      Thus, compensatory mechanisms must limit gross perturbations of electrolyte and
      acid-base balance. Plasma aldosterone is increased in NHE3-deficient mice, and
      expression of both renin and the AE1 (Slc4a1) Cl-/HCO3- exchanger mRNAs are
      induced in kidney. In the colon, epithelial Na+ channel activity is increased and
      colonic H+,K+-ATPase mRNA is massively induced. These data show that NHE3 is the
      major absorptive Na+/H+ exchanger in kidney and intestine, and that lack of the
      exchanger impairs acid-base balance and Na+-fluid volume homeostasis.

PMID- 9662406
TI  - CLN5, a novel gene encoding a putative transmembrane protein mutated in Finnish
      variant late infantile neuronal ceroid lipofuscinosis.
AB  - The neuronal ceroid lipofuscinoses (NCLs) represent a group of common recessive
      inherited neurodegenerative disorders of childhood, with an incidence of 1:12,500
      live births. They are characterized by accumulation of autofluorescent
      lipopigments in various tissues. Several forms of NCLs have been identified,
      based on age at onset, progression of disease, neurophysiological and
      histopathological findings and separate genetic loci. All types of NCL cause
      progressive visual and mental decline, motor disturbance, epilepsy and behavioral
      changes, and lead to premature death. One of the subtypes, Finnish variant late
      infantile neuronal ceroid lipofuscinosis (vLINCL; MIM256731) affects children at
      4-7 years of age. The first symptom is motor clumsiness, followed by progressive
      visual failure, mental and motor deterioration and later by myoclonia and
      seizures. We have previously reported linkage for vLINCL on chromosome 13 (ref.
      5) and constructed a long-range physical map over the region. Here, we report the
      positional cloning of a novel gene, CLN5, underlying this severe neurological
      disorder. The gene encodes a putative transmembrane protein which shows no
      homology to previously reported proteins. Sequence analysis of DNA samples from
      patients with three different haplotypes revealed three mutations; one deletion,
      one nonsense and one missense mutation, suggesting that mutations in this gene
      are responsible for vLINCL.

PMID- 9662407
TI  - Loss of adenylyl cyclase I activity disrupts patterning of mouse somatosensory
      cortex.
AB  - The somatosensory (SI) cortex of mice displays a patterned, nonuniform
      distribution of neurons in layer IV called the 'barrelfield' (ref. 1).
      Thalamocortical afferents (TCAs) that terminate in layer IV are segregated such
      that each barrel, a readily visible cylindrical array of neurons surrounding a
      cell-sparse center, represents a distinct receptive field. TCA arbors are
      confined to the barrel hollow and synapse on barrel-wall neurons whose dendrites
      are oriented toward the center of the barrel. Mice homozygous for the barrelless
      (brl) mutation, which occurred spontaneously in ICR stock at Universite de
      Lausanne (Switzerland), fail to develop this patterned distribution of neurons,
      but still display normal topological organization of the SI cortex. Despite the
      absence of barrels and the overlapping zones of TCA arborization, the size of
      individual whisker representations, as judged by 2-deoxyglucose uptake, is
      similar to that of wild-type mice. We identified adenylyl cyclase type I (Adcy1)
      as the gene disrupted in brl mutant mice by fine mapping of proximal chromosome
      11, enzyme assay, mutation analysis and examination of mice homozygous for a
      targeted disruption of Adcy1. These results provide the first evidence for
      involvement of cAMP signalling pathways in pattern formation of the brain.

PMID- 9662408
TI  - A second-generation screen of the human genome for susceptibility to insulin
      dependent diabetes mellitus.
AB  - During the past decade, the genetics of type 1 (insulin-dependent) diabetes
      mellitus (IDDM) has been studied extensively and the disorder has become a
      paradigm for genetically complex diseases. Previous genome screens and studies
      focused on candidate genes have provided evidence for genetic linkage between
      polymorphic DNA markers and 15 putative IDDM susceptibility loci, designated
      IDDM1-IDDM15. We have carried out a second-generation screen of the genome for
      linkage and analysed the data by multipoint linkage methods. An initial panel of
      212 affected sibpairs (ASPs) was genotyped for 438 markers spanning all
      autosomes, and an additional 467 ASPs were used for follow-up genotyping. Other
      than the well-established linkage with the HLA region at chromosome 6p21.3, there
      was only one region, located on chromosome 1q and not previously reported, where
      the log likelihood ratio (lod) was greater than 3. Lods between 1.0 and 1.8 were
      found in six other regions, three of which have been reported in other studies.
      Another reported region, on chromosome 6q and loosely linked to HLA, also had an
      elevated lod. Little or no support was found for most reported IDDM loci (lods
      were less than 1), despite larger sample sizes in the present study.

PMID- 9662409
TI  - A search for type 1 diabetes susceptibility genes in families from the United
      Kingdom.
AB  - Genetic analysis of a mouse model of major histocompatability complex (MHC)
      associated autoimmune type 1 (insulin-dependent) diabetes mellitus (IDDM) has
      shown that the disease is caused by a combination of a major effect at the MHC
      and at least ten other susceptibility loci elsewhere in the genome. A genome-wide
      scan of 93 affected sibpair families (ASP) from the UK (UK93) indicated a similar
      genetic basis for human type 1 diabetes, with the major genetic component at the
      MHC locus (IDDM1) explaining 34% of the familial clustering of the disease
      (lambda(s)=2.5; refs 3,4). In the present report, we have analysed a further 263
      multiplex families from the same population (UK263) to provide a total UK data
      set of 356 ASP families (UK356). Only four regions of the genome outside
      IDDM1/MHC, which was still the only major locus detected, were not excluded at
      lambda(s)=3 and lod=-2, of which two showed evidence of linkage: chromosome 10p13
      p11 (maximum lod score (MLS)=4.7, P=3x10(-6), lambda(s)=1.56) and chromosome
      16q22-16q24 (MLS=3.4, P=6.5x10(-5), lambda(s)=1.6). These and other novel
      regions, including chromosome 14q12-q21 and chromosome 19p13-19q13, could
      potentially harbour disease loci but confirmation and fine mapping cannot be
      pursued effectively using conventional linkage analysis. Instead, more powerful
      linkage disequilibrium-based and haplotype mapping approaches must be used; such
      data is already emerging for several type 1 diabetes loci detected initially by
      linkage.

PMID- 9662410
TI  - A male-female bias in type 1 diabetes and linkage to chromosome Xp in MHC HLA-DR3
      positive patients.
AB  - It is generally assumed that the male:female (M:F) ratio in patients with type 1
      (insulin-dependent) diabetes mellitus (IDDM) is 1. A recent survey, however,
      revealed that high incidence countries (mainly European) have a high M:F ratio
      and low incidence ones (Asian and African) have a low M:F ratio. We have now
      analysed the M:F ratio according to genotype at the major locus, the major
      histocompatibility complex (MHC; IDDM1). There are two main IDDM1 susceptibility
      haplotypes, HLA-DR3 and -DR4, which are present in 95% of Caucasian cases. We
      report here that in medium/high incidence Caucasian populations from the United
      States of America, United Kingdom and Sardinia (1307 cases), the bias in male
      incidence is largely restricted to the DR3/X category of patients (X not = DR4)
      with a M:F ratio of 1.7 (P=9.3x10(-7)), compared with a ratio of 1.0 in the DR4/Y
      category (Y;DR3). This is additional evidence for significant heterogeneity
      between the aetiology of 'DR4-associated' and 'DR3-associated' diabetes. We
      analysed linkage of type 1 diabetes to chromosome X, and as expected, most of the
      linkage to Xp13-p11 was in the DR3/X affected sibpair families (n=97; peak
      multipoint MLS at DXS1068=3.5, P=2.7x10(-4); single point MLS=4.5, P=2.7x10(-5)).
      This is evidence for aetiological heterogeneity at the IDDM1/MHC locus and,
      therefore, in the search for non-MHC loci in type 1 diabetes, conditioning of
      linkage data by HLA type is advised.

PMID- 9662411
TI  - Induction of rat pancreatic glutathione S-transferase and quinone reductase
      activities by a mixture of glucosinolate breakdown derivatives found in Brussels
      sprouts.
AB  - The chemoprotective effects of cruciferous vegetables against cancer has been
      linked to the induction of detoxification enzymes, including the phase II
      enzymes, glutathione S-transferases (GST) and quinone reductase (QR). Four
      glucosinolate breakdown products found in Brussels sprouts and previously shown
      individually to affect detoxification enzymes--(1-cyano-2-hydroxy-3-butene
      (Crambene), indole-3-carbinol (I3C), phenylethyl isothiocyanate (PEITC) and 1
      isothiocyanato-3-(methylsulfinyl)-propane (IBN) were administered to male F344
      rats by oesophageal intubation for 7 days both as a mixture and individually to
      assess the effect of these compounds on GST and QR activity in the pancreas, an
      organ previously shown to be affected by cruciferous diets. The doses of each
      compound in the mixture (50 mg Crambene/kg, 56 mg I3C/kg, 0.1 mg PEITC/kg and 38
      mg IBN/kg) were chosen to represent the relative proportions of the parent
      glucosinolate for each compound in Brussels sprouts and shown to be below the
      toxic threshold for all the compounds. In rats receiving the mixture, pancreatic
      QR and GST activities were elevated 31- and 1.7-fold, respectively, while
      glutathione (GSH) was elevated threefold. On an individual basis, Crambene alone
      caused a 21-fold elevation of QR and 1.5-fold elevation of GST activities, while
      pancreatic GSH was elevated by both Crambene and PEITC 2.6- and twofold,
      respectively. No other significant effects of individual components were found.
      When the mixture was administered at 60% of the original dose, pancreatic QR and
      GST activities were elevated 12- and 1.4-fold, respectively, and pancreatic GSH
      was elevated 1.5-fold. At 20% of the original dose, pancreatic GSH was unaffected
      and QR and GST activities were elevated 2.7- and 1.3-fold, respectively. The
      results of these studies suggest that a diet rich in cruciferous vegetables may
      produce phase 11 enzyme induction in the pancreas, and that Crambene may be the
      most active component.

PMID- 9662412
TI  - Inhibition of mouse and human CYP 1A- and 2E1-dependent substrate metabolism by
      the isoflavonoids genistein and equol.
AB  - The inhibitory effect of the isoflavonoids genistein and equol on cytochrome P450
      activities has been investigated. Genistein and equol inhibited the high capacity
      component of p-nitrophenol (CYP2E1 substrate) metabolism in liver microsomes from
      acetone-induced mice with IC50 values of approximately 10 mM and 560 microM,
      respectively (cf. diethyldithiocarbamate, IC50, 69 microM). Using human CYP2E1
      from a specific expression system (which overcame multienzyme involvement in the
      rodent system), non-competitive inhibition was also seen with both isoflavonoids.
      Genistein and equol also inhibited the high capacity component of ethoxyresorufin
      (CYP1A substrate) metabolism in liver microsomes from beta-naphthoflavone-induced
      mice with IC50 values of 5.6 mM and 1.7 mM, respectively (cf. alpha
      naphthoflavone, IC50 0.8 microM). Using human CYPIA2 from a specific expression
      system, noncompetitive inhibition was seen with both isoflavonoids. CYP1A1
      inhibition offers a possible explanation for the chemopreventative effect of
      genistein against, for example, dimethylbenz[a]anthracene genotoxicity reported
      in animals but the IC50 values negate the relevance of this specific
      chemopreventative action at the levels likely to be achieved from the human diet.

PMID- 9662413
TI  - Developmental toxicology of solamargine and solasonine glycoalkaloids in frog
      embryos.
AB  - As part of an effort to improve the safety of plant foods, a need exists to
      define the relative toxicities of structurally different glycoalkaloids and
      metabolites which may be present in Solanum plant species such as potatoes,
      tomatoes and eggplants. The objectives of this study were to determine the
      relative toxicities and the modes of action of the eggplant (Solanum melongena)
      glycoalkaloids solamargine and solasonine in Xenopus laevis frog embryos, using
      membrane potential and embryo growth and teratogenicity assays. In the cell
      membrane assays, adverse effects on embryos were evaluated by measuring membrane
      potentials using an electrochromic dye, di-4-ANEPPS, as a fluorescence probe for
      the integrity of the membranes. In the embryo growth and teratogenesis assays,
      the survival of the embryos and organ malformations was used as an index of
      embryo toxicity. The relative potencies of glycoalkaloids are similar for frog
      embryo effects (survival and teratogenicities) and for membrane effects (membrane
      potential). Experiments with solasonine at pH 6 and 8 suggest that the
      unprotonated form of the glycoalkaloids appears to be involved in the membrane
      effects. The nature of the carbohydrate side-chains of the steroidal glycosides
      governs relative potencies. The possible significance of the findings to food
      safety and plant physiology and possible application of the membrane assays to
      bacterial toxins are discussed.

PMID- 9662414
TI  - Toxicological evaluation of dietary conjugated linoleic acid in male Fischer 344
      rats.
AB  - To assess the toxicity of conjugated linoleic acid (CLA) after an extended
      feeding period, 40 male Fischer 344 rats were given either a basal diet (control)
      or the same diet supplemented with 1.5% CLA. During the 36-wk study, food
      disappearance, body weights, and cageside examinations were determined weekly and
      were found to be unaffected by CLA treatment. On termination, 15 major organs
      from 10 animals in each treatment group were excised, weighed, and prepared for
      histopathological evaluation. Results indicated no treatment-related effects.
      Likewise, haematological analysis of collected cardiac blood did not reveal any
      significant difference. The average daily intake of CLA by rats in this study was
      80-fold and 50-fold greater than the estimated 50th and 90th percentile daily
      intakes, respectively, for teenage boys. Hence, results from this study indicate
      a lack of toxicity and support the potential determination for the GRAS status of
      CLA.

PMID- 9662415
TI  - Effects of fumonisin B1 in pregnant rats.
AB  - Fumonisin B1 (FB1), the major mycotoxin from Fusarium moniliforme, has been
      implicated as a causative agent in several animal and human diseases. Despite
      animal toxicity studies and human epidemiological studies of FB1, knowledge of
      its reproductive effects is scarce. In this study, one of a series of proposed
      studies that will allow extrapolation to humans, pregnant rats were given oral
      doses of 0, 1.875, 3.75, 7.5 or 15 mg FB1/kg on gestation days 3 16. Caesarean
      sections were performed on day 17 or 20, and maternal condition, implantation
      efficiency, foetal viability and foetal development were measured. Dose-related
      decreases in overall feed consumption and body weight gain were seen, but only
      the feed consumption decrease at 15 mg/kg, and the decreased body weight gain at
      15 mg/kg on days 0-17 were statistically significant. Foetal body weights at day
      17 were similar in control and treated groups; but in day-20 foetuses, female
      weight and crown-rump length were significantly decreased at 15 mg/kg. FB1 was
      not teratogenic at the doses tested, and no dose-related effects were seen in
      either skeletal or soft-tissue development. In day-17 animals, maternal and
      foetal brain, liver and kidney tissues, and maternal serum were preserved to
      study the levels of sphinganine (Sa), sphingosine (So), and the Sa/So ratios.
      Dose-related increases were seen in Sa/So ratios in maternal livers, kidneys and
      serum. Sa/So ratios of maternal brains were not affected, nor were those of
      foetal kidneys, livers or brains.

PMID- 9662416
TI  - Modulation of IL-1beta, IL-6 and TNF-alpha secretion and mRNA expression by the
      trichothecene vomitoxin in the RAW 264.7 murine macrophage cell line.
AB  - Oral exposure of mice to vomitoxin (VT) has been previously shown to enhance gene
      expression of several cytokines associated with macrophage activation. Here, the
      effects of exposure to VT in vitro on cytokine secretion and mRNA expression were
      determined in the murine macrophage cell line RAW 264.7. Enzyme-linked
      immunosorbent assay (ELISA) of supernatants revealed that significant increases
      in secreted tumour necrosis factor alpha (TNF-alpha) were observed 2 days after
      exposure to VT at 100 ng/ml and 250 ng/ml, both with and without
      lipopolysaccharide (LPS) activation. While VT did not affect IL-6 secretion in
      the absence of LPS, significantly increased IL-6 production was observed in
      culture supernatants after 1, 2 and 5 days of exposure to VT at 250 ng/ml in the
      presence of LPS. Soluble IL-1beta was not detected in control or VT-treated cell
      cultures with or without LPS activation. Immunochemical staining of intracellular
      cytokines in conjunction with flow cytometric analysis was used to detect the
      effects of VT on the percentage of positive cells and output per cell. The
      percentage of cells that produced intracellular TNF-alpha were significantly
      increased at 100 and 250 ng/ml VT with and without LPS whereas increased IL-6
      output per cell was observed at 100 and 250 ng/ml VT with LPS. To assess the
      effects of VT on cytokine mRNA expression, RAW 264.7 cells were analysed semi
      quantitatively using reverse transcription-polymerase chain reaction(RT-PCR) in
      conjunction with Southern hybridization analysis. Elevated TNF-alpha mRNA was
      observed at 100 and 250 ng VT/ml at 6 and 24 hr in the absence of LPS. With the
      addition of LPS, superinduction of TNF-alpha was not observed in the presence of
      VT. Increased IL-1beta and IL-6 mRNAs were observed at 100 and 250 ng VT/ml at 24
      hr in the presence of LPS. These results demonstrated that VT could superinduce
      both cytokine secretion and mRNA levels in macrophage cultures.

PMID- 9662417
TI  - Oral teratogenicity studies of methyl bromide in rats and rabbits.
AB  - Teratogenicity studies of methyl bromide, a widely used fumigant, were conducted
      in rats and rabbits. Methyl bromide was dissolved in corn oil and administered
      orally to groups of 24 copulated female Crj:CD (SD) rats at dose levels of 0
      (corn oil), 3, 10 or 30 mg/kg/day on days 6-15 of gestation and to groups of 18
      artificially inseminated female Kbl:JW rabbits at 0, 1, 3 or 10 mg/kg/day on days
      6-18 of gestation. Maternal rats and rabbits were euthanized on respective days
      20 and 27 of gestation. Foetuses were examined for survival, growth and
      teratological alterations. Maternal toxicity was evident in the high-dose groups
      for both species. In these groups, maternal body weight gains and food
      consumption were significantly decreased during the dosing and post-dosing
      periods. Necropsy of maternal rats also revealed erosive lesions in the stomach
      and the surrounding organs. However, no treatment-related adverse effects were
      found in foetuses of the treated groups for both rat and rabbit studies. These
      results led to the conclusion that methyl bromide was not foetotoxic or
      teratogenic to rat and rabbit foetuses up to dose levels of 30 and 10 mg/kg/day,
      respectively, at which maternal toxicity was evident for both species.

PMID- 9662418
TI  - 2-Ethylhexanoic acid: subchronic oral toxicity studies in the rat and mouse.
AB  - Groups of 10 male and 10 female Fischer 344 rats and B6C3F1 mice were fed diets
      containing either 0.0, 0.1, 0.5 or 1.5% 2-ethylhexanoic acid (EHA) for 13 wk.
      Additional groups of 10 male and 10 female rats or mice. were fed either 0.0 or
      1.5% EHA for 13 wk followed by a 4-wk recovery (non-treatment) period. Based on
      food consumption and body weight, the EHA diets provided doses of 61, 303 or 917
      mg/kg/day for male rats and 71, 360 or 1068 mg/kg/day for female rats. The EHA
      diets provided doses of 180, 885 or 2728 mg/kg/day for male mice and 205, 1038 or
      3139 mg/kg/day for female mice. No mortality or significant clinical signs of
      toxicity were observed during the study. Body weights and food consumption of
      both rats and mice fed 1.5% EHA were lower beginning after the first week of
      treatment, consistent with a reduction in food consumption. Other groups were
      unaffected by treatment. After 13 wk, lower triglyceride levels occurred in male
      mice fed 1.5% EHA and female mice fed 0.5 or 1.5% EHA, but not in other groups.
      Cholesterol levels were higher in all male rat test groups and in female rats and
      male and female mice fed either 0.5 or 1.5% EHA, although this effect was
      reversible following a 28-day recovery period. The principal effects of EHA
      involved the liver or metabolic processes associated with the liver. The 0.5 and
      1.5% diets in both rats and mice were associated with increased relative liver
      weight and histological changes in hepatocytes, specifically hepatocyte
      hypertrophy and reduced cytoplasmic vacuolization. Observed histopathological and
      clinical pathological changes were reversible following recovery. These results
      indicate that EHA does not produce persistent. overt toxicity in rats or mice
      following subchronic dietary exposure at concentrations up to 1.5% in feed. The
      no-observed-adverse-effect level (NOAEL) for male rats was 61 mg/kg/day and the
      no-observed-effect level (NOEL) for female rats was 71 mg/kg/day, while 180 and
      205 mg/kg/day represent NOELs for male and female mice, respectively.

PMID- 9662419
TI  - Role of cytochrome P-450 in quinalphos toxicity: effect on hepatic and brain
      antioxidant enzymes in rats.
AB  - Quinalphos (QP), an organophosphate pesticide, is used in controlling the pests
      of a variety of crops. To understand the mechanism of the metabolic basis of the
      toxicity of QP it was thought pertinent to study the role of cytochrome P-450
      (P450) and antioxidant enzyme systems. Albino rats treated orally with QP (0.52
      and 1.04 mg/kg body weight) for 60 days showed a significant decrease in body,
      brain and liver weights. Hepatic P450 content and its dependent monooxygenases,
      namely aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin-O-deethylase (ERD),
      were induced to 1.8-2.5-fold, while neuronal AHH was induced to 1.8-fold
      following QP treatment (1.04 mg/kg) to animals. The hepatic antioxidant defence
      system, comprising catalase, glutathione (GSH) reductase, superoxide dismutase
      (SOD) and GSH peroxidase, was also significantly increased in QP-treated animals,
      while in the brain only catalase was increased and GSH reductase decreased. There
      was no significant change in hepatic GSH content and lipid peroxide levels in QP
      treated animals at any dose group in comparison with the control group.
      Pretreatment of rats with phenobarbitone (PB) or 3-methylcholanthrene (MC) (P450
      inducers) prevented mortality caused by the LD50 dose of QP, whereas pretreatment
      with cobalt chloride (a P450 inhibitor) enhanced the mortality rate to 100%
      within 3 days. From the above study it can be inferred that the toxicity of QP
      may be due to the parent compound or its metabolite(s) produced prior to P450
      oxidation and that the induction of P450 system by QP may be a defence mechanism.

PMID- 9662420
TI  - A 4-year study of plasma ochratoxin A in a selected population in Tokyo by
      immunoassay and immunoaffinity column-linked HPLC.
AB  - Employing a competitive ELISA (cELISA) based on monoclonal antibody and a novel
      immunoaffinity-column (IAC)-linked HPLC-fluorometry, ochratoxin A (OTA) levels in
      the plasma of 184 healthy volunteers (130 males, 54 females) were surveyed in
      Tokyo during the 4 years from 1992 to 1996. It was found that 85% of the cases
      were positive for OTA except 38% in 1994, and an average value in the positives
      was estimated as 68 pg/ml. This suggests that the population in Tokyo is exposed
      to OTA at high frequency, although the level in plasma is far less than that
      reported in Europe and Canada. A partial contribution of fermented dietary
      foodstuffs, coffee and wine is suspected as the source of the OTA observed in the
      human plasma.

PMID- 9662421
TI  - The sex ratio of offspring of female rhesus monkeys exposed to Aroclor 1254.

PMID- 9662422
TI  - Involvement of microsomal fatty aldehyde dehydrogenase in the alpha-oxidation of
      phytanic acid.
AB  - We investigated the role of microsomal fatty aldehyde dehydrogenase (FALDH) in
      the conversion of pristanal into pristanic acid. Cultured skin fibroblasts from
      controls and patients with Sjogren-Larsson syndrome (SLS) who are genetically
      deficient in FALDH activity were incubated with [2,3-(3)H]phytanic acid. The
      release of aqueous-soluble radioactivity by the SLS cells was decreased to 25% of
      normal, consistent with an intact formation of pristanal but a deficiency of
      further oxidation. SLS cells also accumulated four-fold more radioactivity in N
      alkyl-phosphatidyl ethanolamine, which arises from incorporation of free aldehyde
      into phosphatidyl ethanolamine. Recombinant human FALDH expressed in Chinese
      hamster ovary cells readily oxidized pristanal and cultured fibroblasts from SLS
      patients showed a severe deficiency in FALDH activity (13% of normal) when
      pristanal was used as substrate. Nevertheless, SLS patients did not accumulate
      phytanic acid in their plasma. We conclude that FALDH is involved in the
      oxidation of pristanal to pristanic acid and that this reaction is deficient in
      patients with SLS.

PMID- 9662423
TI  - Phospholipase C-gamma, protein kinase C and Ca2+/calmodulin-dependent protein
      kinase II are involved in platelet-derived growth factor-induced phosphorylation
      of Tiam1.
AB  - In Swiss 3T3 fibroblasts, the Rac1-specific guanine nucleotide exchange factor
      Tiam1 is phosphorylated by several different agonists. We show here that PDGF
      induces threonine phosphorylation of Tiam1 in a time- and dose-dependent manner.
      Tiam1 phosphorylation was significantly reduced by the selective protein kinase C
      inhibitor Ro-31-8220 and by KN93, an inhibitor of Ca2+/calmodulin-dependent
      protein kinase II. The Ca2+ chelator BAPTA/AM totally abrogated Tiam1
      phosphorylation, indicating that Ca2+ is essential for this phosphorylation.
      Moreover, PDGF-stimulated Tiam1 phosphorylation was markedly reduced by 72 +/-
      10% in PLC-gamma1 deficient mouse fibroblasts, compared to wild-type cells,
      indicating that phosphoinositide phospholipase C is involved.

PMID- 9662424
TI  - Efficacy of a novel metalloprotease inhibitor on botulinum neurotoxin B activity.
AB  - The novel inhibitor 7-N-phenylcarbamoylamino-4-chloro-3-propyloxyisocoumarin (ICD
      1578) was tested for its ability to antagonize the zinc metalloprotease activity
      of botulinum toxin B (BoNT/B). The efficacy of this compound was tested in a cell
      free system using a 50-mer synaptobrevin peptide as substrate. The peptide,
      designated as [Pya88] S 39-88, had a fluorescent amino acid analog, L
      pyrenylalanine (Pya), substituted for the normal Phe88 of synaptobrevin-2.
      Cleavage by BoNT light chain yielded fragments of 38 and 11 amino acids,
      respectively. The smaller fragment, containing the Pya fluorophore, was readily
      separated and quantified by fluorescence spectroscopy at 377 nm. In the presence
      of 7-200 microM ICD 1578, cleavage of [Pya88] S 39-88 was progressively reduced
      (IC50 = 27.6 microM), and 100 microM ICD 1578 produced >95% inhibition. For
      comparison, captopril, a well-known zinc metalloprotease inhibitor, generated
      less than 10% inhibition at a concentration of 5 mM. ICD 1578 is the most potent
      antagonist of BoNT/B light chain thus far described.

PMID- 9662425
TI  - Chloramine T-induced structural and biochemical changes in echistatin.
AB  - Echistatin is a member of the disintegrin family of peptides and a potent
      inhibitor of platelet aggregation and cell adhesion. Echistatin binds to integrin
      alpha(v)beta3 and alpha(IIb)beta3 receptors with high affinity. Binding is
      mediated by an RGD-containing loop maintained in an appropriate conformation by
      disulfide bridges. In this study, we have compared the binding characteristics of
      echistatin iodinated by either lactoperoxidase or chloramine T method. We show
      that echistatin labeled by lactoperoxidase method binds to integrin alpha(v)beta3
      receptor with high affinity and in a non-dissociable manner very similar to
      native echistatin. In contrast, chloramine T-labeled echistatin can rapidly
      dissociate from the receptor. We demonstrate that chloramine T reaction results
      in the addition of an extra oxygen to the methionine residue adjacent to the RGD
      motif in echistatin. Modeling studies and molecular dynamic simulation studies
      show that the extra oxygen atom on the methionine residue can form hydrogen bonds
      with the glycine and aspartic acid residues of the RGD motif. These structural
      changes in echistatin help explain the changes in the binding characteristics of
      the molecule following chloramine T reaction.

PMID- 9662426
TI  - Role of MAP kinase cascades in inducing arginine transporters and nitric oxide
      synthetase in RAW264 macrophages.
AB  - Bacterial lipopolysaccharide (LPS) in the presence of interferon gamma (IFNgamma)
      stimulates the synthesis of the cationic amino acid transporter 2B (CAT-2B) and
      inducible nitric oxide synthetase (iNOS) in RAW264 macrophages, which are thought
      to underlie the increased rate of arginine uptake into these cells and its
      conversion to nitric oxide, respectively. Here I demonstrate that the LPS- and
      IFNgamma-induced increase in arginine uptake into RAW264 cells is partially
      suppressed in the presence of PD 98059, partially suppressed in the presence of
      SB 203580, and completely inhibited by both drugs. In contrast, the LPS- and
      IFNgamma-induced synthesis of CAT-2B mRNA and iNOS protein is unaffected by PD
      98059 and SB 203580. The results indicate that the MAPK/ERK and SAPK2/p38
      cascades are both rate-limiting for LPS- and IFNgamma-stimulated arginine uptake,
      but not for iNOS synthesis. They also suggest that PD 98059 and SB 203580
      suppress CAT-2B synthesis at a post-transcriptional level.

PMID- 9662427
TI  - Retinoic acid regulates selectively the expression of immediate early response
      genes in PC12 cells.
AB  - Nerve growth factor (NGF) induces neuronal differentiation and growth arrest in
      PC12 cells. One of the initial effects of NGF in these cells is the induction of
      the expression of immediate early genes (IEGs). In this study we have analyzed
      the influence of retinoic acid (RA), which exerts important effects on PC12 cell
      proliferation and function, on the expression of IEGs. Incubation with RA did not
      alter NGFI-A mRNA levels, but significantly reduced the NGFI-B and c-fos response
      to NGF and serum. The response to NGF was maximal in the presence of
      cycloheximide, and RA also reduced the superinduction of NGFI-B and c-fos mRNA
      levels. Sequences contained within the 5' flanking region of the c-fos gene
      confer responsiveness to NGF and mediate the inhibitory effect of RA. The
      differential regulation by RA suggests that NGF induces expression of the three
      IEGs by different mechanisms.

PMID- 9662428
TI  - Expression of Arabidopsis response regulator homologs is induced by cytokinins
      and nitrate.
AB  - We examined cytokinin and nitrate responsiveness in gene expression of five
      distinct response regulator homologs (ARR3-ARR7) in the leaves of nitrogen
      starved Arabidopsis plants. The transcripts accumulated after spraying the shoots
      with t-zeatin. The induction of accumulation was highly specific for cytokinins.
      The transcripts also accumulated by supply of nitrate to the culture medium.
      These findings suggest that ARRs are involved in inorganic nitrogen signal
      transduction mediated by cytokinin as in the case of ZmCip1, a response regulator
      homolog recently identified in maize.

PMID- 9662429
TI  - Molecular cloning, tissue distribution and androgen regulation of rat protein C
      inhibitor.
AB  - Protein C inhibitor (PCI) is the plasma serine protease inhibitor of activated
      protein C, the active enzyme of the anticoagulant protein C pathway. Recently,
      PCI was also detected in human seminal plasma and reproductive organs (testis,
      seminal vesicle and prostate) suggesting that PCI may also play an important role
      in the reproductive system. In this study, we cloned the full length of rat PCI
      cDNA, and determined its amino acid sequence and tissue distribution. We also
      evaluated the effect of androgen on PCI mRNA expression in seminal vesicles and
      testes. The isolated 2074-bp rat PCI cDNA was composed of a 47-bp 5'-non-coding
      region, a 1218-bp coding region of a 406-amino acid precursor protein, a stop
      codon and a 806-bp 3'-non-coding region. The deduced amino acid sequence of rat
      PCI showed 85.7%, 64.1% and 62.2% homology with that of mouse, rhesus monkey and
      human PCIs, respectively. Northern blot analysis showed that the rat PCI mRNA is
      expressed strongly in the seminal vesicle, moderately in the testis, but not in
      the liver. PCI mRNA expression in seminal vesicles and testes was found to
      increase during the process of development, suggesting that it is under androgen
      control. Subsequently, we examined the effect of castration and/or treatment with
      17beta-estradiol or testosterone on PCI mRNA expression in the mature rat seminal
      vesicles. The PCI mRNA expression in seminal vesicles was significantly decreased
      after castration or 17beta-estradiol treatment. Testosterone itself did not
      affect PCI mRNA expression, but treatment in castrated rats significantly
      enhanced its mRNA expression. These findings suggest that the PCI gene expression
      in rat seminal vesicles is regulated by androgen.

PMID- 9662430
TI  - A novel peptide, PLAEIDGIELTY, for the targeting of alpha9beta1-integrins.
AB  - Targeting gene therapy vectors to abundant receptors on airway epithelia may
      allow a significant enhancement of gene delivery and thereby be of particular
      importance for the gene therapy of cystic fibrosis. Alpha9beta1-integrins are
      highly expressed throughout the human airway epithelia in vivo, irrespective of
      any particular clinical status. Aiming to improve the targeting of our non-viral
      integrin-mediated gene transfer systems to airway epithelia, we searched for a
      short tenascin C-derived peptide which would bind to these integrins. By
      utilizing recombinant bacteriophages that display overlapping regions of the
      third fibronectin type III repeat of tenascin C (TNfn3), we were able to localize
      its alpha9beta1-integrin binding site to the B-C loop of TNfn3. A synthetic Pro
      Leu-Ala-Glu-Ile-Asp-Gly-Ile-Glu-Leu-Thr-Tyr peptide (PLAEIDGIELTY) was shown to
      displace alpha9beta1-integrin-expressing cells completely from binding to TNfn3.
      This peptide, therefore, may prove useful both for the examination of the
      functional importance of alpha9beta1-integrins in vivo and the development of
      gene therapy vectors or drugs targeting these integrins.

PMID- 9662431
TI  - Defective intracellular activity of GDP-D-mannose-4,6-dehydratase in leukocyte
      adhesion deficiency type II syndrome.
AB  - Leukocyte adhesion deficiency type II (LAD II) is a rare genetic disease
      characterized by severe immunodeficiency which is related to defective expression
      in leukocytes of sialyl-Lewis X (SLeX), a fucosylated ligand for endothelial
      selectins. The molecular basis of LAD II is still unknown, but has been
      tentatively localized in the de novo pathway of GDP-L-fucose biosynthesis from
      GDP-D-mannose. Here, we demonstrate that in cell lysates from a LAD II patient,
      GDP-D-mannose-4,6-dehydratase (GMD), the first of the two enzymes of the pathway
      has a defective activity compared to control subjects. GMD in cell lysates from
      both parents showed intermediate activity levels. Cloning of GMD from patient and
      control lymphocytes ruled out any mutation affecting the amino acid GMD sequence
      and the purified recombinant proteins from both controls and the patient showed
      identical specific activities. Since the levels of immunoreactive GMD in cell
      lysates were comparable in the patient and in controls, the biochemical
      deficiency of intracellular GMD activity in LAD II seems to be due to mutation(s)
      affecting some still unidentified GMD-regulating protein.

PMID- 9662432
TI  - Growth inhibition by overexpression of human DEAD box protein rck/p54 in cells of
      a guinea pig cell line.
AB  - We transfected cells of a guinea pig cell line with RCK cDNA inserted in a
      pIRES1neo expression vector. The overexpression of rck/p54 was confirmed by
      Western blot and RT-PCR analysis. In two clones expressing rck/p54, the cell
      growth was highly inhibited; and their anchorage-independent growth, which is an
      important character of malignant transformation, was not found. These findings
      are the first evidence that the overexpression of a DEAD box protein/RNA helicase
      could inhibit substantially cell growth at the translational level.

PMID- 9662433
TI  - Immunoglobulin superfamily members gp65 and gp55: tissue distribution of
      glycoforms.
AB  - Gp65 and gp55 are immunoglobulin superfamily members produced by alternative
      splicing of the same gene transcript, and originally identified as components of
      synaptic membranes. A monoclonal antibody specific for gp65 and gp55 has been
      used to detect immunoreactive species in a wide range of tissues. All
      immunoreactive species bind to concanavalin A and deglycosylation studies show
      that in all tissues tested other than brain the immunoreactive species are
      derived from gp55. HEK cells transfected with gp65 or gp55 express different
      glycoforms from brain showing that the pattern of glycosylation of these
      molecules is dependent upon the cell type in which they are expressed.

PMID- 9662434
TI  - Biochemical and functional analysis of highly phosphorylated forms of c-Jun
      protein.
AB  - We report here that, upon UV irradiation or growth stimulation, endogenous c-Jun
      (40 kDa) in chicken embryo fibroblasts (CEF) is converted into several forms with
      apparently higher molecular weights in SDS-polyacrylamide gel electrophoresis
      (45, 44, 42 kDa). Two of the bands (44 and 45 kDa) were transient after growth
      stimulation, but were much more persistent after UV irradiation. In both cases,
      the drastic mobility shifts were accompanied with the activation of endogenous
      JNK activity but not of MAPK activity, and the bands were shown to represent
      different phosphorylation states of c-Jun rather than ubiquitinated c-Jun.
      Biochemical analysis indicated that phosphorylation at Ser63 and Ser73 was not
      sufficient to produce these drastic mobility shifts, which additionally required
      phosphorylation at Thr91 and Thr93. Substitution of both Ser63 and Ser73 with
      either Ala or Asp had no significant effect on the transforming activity of c
      Jun, but the mutants failed to show drastic mobility shifts even after UV
      irradiation. These results indicate that Ser63 and Ser73 are essential for the
      drastic mobility shifts and further suggest that the highly phosphorylated forms
      of c-Jun are not directly involved in cellular transformation.

PMID- 9662435
TI  - Characterisation of a new rubredoxin isolated from Desulfovibrio desulfuricans
      27774: definition of a new family of rubredoxins.
AB  - A new rubredoxin from the sulphate-reducing bacterium Desulfovibrio desulfuricans
      ATCC 27774, grown with nitrate as terminal electron acceptor, was isolated and
      characterised. The protein is an 8.5 kDa monomer containing one iron atom per
      molecule, with a reduction potential of 25 +/- 5 mV at pH 7.6. Like the
      recombinant Rdl protein from D. vulgaris, expressed in Escherichia coli [Lumpio,
      H.L., Shenvi, N.V., Garg, R.P., Summers, A.O. and Kurtz, D.M., J. Bacteriol. 179
      (1997) 4607-4615], it contains an unusual spacing of four amino acids between the
      first two of the iron coordinating cysteinyl residues. This difference is
      reflected in the structure of the iron centre, as observed by visible and EPR
      spectroscopies. All together, these features make these proteins the first
      members of a new family of rubredoxins.

PMID- 9662436
TI  - Interleukin-1 receptor accessory protein interacts with the type II interleukin-1
      receptor.
AB  - Stably transfected HEK-293 cells express on their surface the murine type II IL-1
      receptor (mIL-1RII) as demonstrated by FACS analysis using the mAb 4E2, however
      binding of [125I]-hrIL-1beta to these cells is nearly absent. Saturable high
      affinity binding of [125I]-hrIL-1beta is observed when the murine IL-1 receptor
      accessory protein (mIL-1RAcP) is coexpressed with mIL-1RII. Binding of [125I]
      hrIL-1beta to mIL-1RII-mIL-1RAcP complex can be inhibited either with antibodies
      to mIL-1RII (mAb 4E2), or by antibodies to mIL-1RAcP (mAb 4C5). The number of
      high affinity binding sites in cells stably transfected with the cDNA for mIL
      1RII is dependent on the dose of cDNA for mIL-1RAcP used to transfect the cells.
      The high affinity complex between mIL-1RII and mIL-1RAcP is not preformed by
      interaction between the intracellular domains of these two transmembrane
      proteins, rather it appears to require the extracellular portions of mIL-1RII and
      mIL-1RAcP and the presence of a ligand. We suggest that in addition to its
      earlier described decoy receptor role, IL-1RII may modulate the responsiveness of
      cells to IL-1 by binding the IL-1RAcP in unproductive/non-signalling complexes
      and thus reducing the number of signalling IL-1RI-IL-1RAcP-agonist complexes when
      IL-1 is bound.

PMID- 9662437
TI  - Effects of IL-1 receptor accessory protein on IL-1 binding.
AB  - Interleukin-1 (IL-1) is an important pro-inflammatory cytokine that exerts its
      diverse biological functions by binding to a receptor complex consisting of two
      transmembrane proteins, type I IL-1 receptor (IL-1RI) and IL-1 receptor accessory
      protein (IL-1RAcP). Both receptor chains are indispensable for IL-1 signaling,
      but only IL-1RI is able to bind the cytokine. The effects of IL-1RAcP on IL-1
      binding are unclear. This study shows that although expression of IL-1RAcP does
      not alter the equilibrium dissociation constant of IL-1, it has an effect on the
      non-equilibrium binding modus, most likely due to changes in on/off rates. This
      defines an additional function of IL-1RAcP: it stabilizes the active IL-1
      receptor complex.

PMID- 9662438
TI  - Human/mouse interleukin-1 receptor/receptor accessory protein interactions in IL
      1beta-induced NFkappaB activation.
AB  - We examined whether functional heterologous complexes between human IL-1RI (hIL
      1RI) and murine IL-1R accessory protein (mIL-1RAcP) can be formed, utilizing
      human fibroblast HEK 293 cells and murine fibroblast C127 cells, nontransfected
      or stably transfected with hIL-1RI (C127-hIL-1RI), respectively. In non
      transfected C127 cells, IL-1beta signalled through the mIL-1RI-mIL-1RAcP complex
      and activated NFkappaB p50/p65 heterodimers. In C127-hIL-1RI cells, IL-1beta
      signalled through the hIL-1RI and activated both p65/p65 and p50/p65 NFkappaB
      complexes, where only the activation of NFkappaB p65/p65 was dependent on mIL
      1RAcP. Thus, clearly both homologous and heterologous IL-1RI-IL-1RAcP
      interactions support NFkappaB translocation, but with differences in signalling
      pattern.

PMID- 9662439
TI  - All three surface tryptophans in Type IIa cellulose binding domains play a
      pivotal role in binding both soluble and insoluble ligands.
AB  - The three surface tryptophans of the Type IIa cellulose binding domain of
      Pseudomonas fluorescens subsp. cellulosa xylanase A (CBD(XYLA)) were
      independently mutated to alanine, to create the mutants W13A, W49A and W66A. The
      three mutant proteins were purified, and their capacity to bind to a variety of
      ligands was determined. The mutant proteins have native-like structures but
      exhibited much weaker affinity for crystalline and amorphous cellulose and for
      cellohexaose than the wild type. These data indicate that all three tryptophans
      are important for binding to cellulose, and support a model in which the three
      tryptophans form an aromatic strip on the surface of the protein that binds to a
      single cellulose.

PMID- 9662440
TI  - Complex formation between calsequestrin and the ryanodine receptor in fast- and
      slow-twitch rabbit skeletal muscle.
AB  - Linkage between the high-capacity Ca2+-binding protein calsequestrin and the
      ryanodine receptor is proposed to be essential for proper Ca2+-release during
      skeletal muscle excitation-contraction coupling. However, no direct biochemical
      evidence exists showing a connection between these high-molecular-mass complexes
      in native skeletal muscle membranes. Here, using immunoblot analysis of
      chemically crosslinked membrane vesicles enriched in triad junctions, we have
      demonstrated that a very close neighborhood relationship exists between
      calsequestrin and the ryanodine receptor in both main fiber types. Hence, the
      luminal Ca2+-reservoir complex appears to be directly coupled to the membrane
      Ca2+-release complex and oligomerization seems to be of functional importance.

PMID- 9662441
TI  - Differential binding of human blood group Sd(a+) and Sd(a-) Tamm-Horsfall
      glycoproteins with Dolichos biflorus and Vicia villosa-B4 agglutinins.
AB  - The binding patterns of human blood group Sd(a+) and Sd(a-) Tamm-Horsfall
      glycoproteins (THGPs) with respect to four GalNAc specific agglutinins were
      studied by quantitative precipitin assay (QPA) and enzyme linked lectinosorbent
      assay (ELLSA). Of the native and asialo Sd(a+) and Sd(a-) THGP tested by QPA and
      ELLSA, only native and asialo Sd(a+) bound well with Dolichos biflorus (DBA) and
      Vicia villosa-B4 (VVA-B4), while Sd(a-) THGP reacted poorly with these two
      lectins. Neither Sd(a+) nor Sd(a-) THGPs reacted with two other GalNAc alpha
      anomer specific lectins: Codium fragile subspecies tomentosoides and Artocarpus
      integrifolia. Furthermore, the binding of asialo Sd(a+)THGP-VVA-B4 and native
      Sd(a+)THGP-DBA through GalNAc beta--> was confirmed by inhibition assay. These
      results demonstrate that DBA and VVA-B4 are useful reagents to differentiate
      between Sd(a+) and Sd(a-) THGP.

PMID- 9662442
TI  - A heat shock-related protein, p20, plays an inhibitory role in platelet
      activation.
AB  - Some low molecular mass heat shock proteins (HSPs) appear to act as molecular
      chaperones, but their exact physiological roles have not been fully elucidated.
      We reported previously that a 20-kDa protein (p20), which is classified as a low
      molecular mass HSP, is present at high levels in skeletal and smooth muscles. In
      the present study, we investigated a physiological role of p20 on platelet
      function in vitro and ex vivo. p20 inhibited platelet aggregation using human
      platelets dose-dependently induced by botrocetin. On the other hand, HSP27, the
      other type of low molecular mass HSP, did not affect platelet aggregation. When
      p20 (300 microg/kg) was injected intravenously as a bolus in hamsters, platelet
      aggregation ex vivo induced by botrocetin was also significantly inhibited. In
      order to further investigate the inhibitory effect by p20 on platelet activation,
      we performed platelet aggregation induced by thrombin or ADP using human
      platelets. p20 markedly prevented platelet aggregation induced by thrombin, but
      not ADP. These findings suggest that p20 can act intercellularly to regulate
      platelet functions. Our results may provide the basis for a novel defensive
      system to thrombus formation.

PMID- 9662443
TI  - Chromosomal localization, genomic organization, and developmental expression of
      the murine caveolin gene family (Cav-1, -2, and -3). Cav-1 and Cav-2 genes map to
      a known tumor suppressor locus (6-A2/7q31).
AB  - Caveolins (Cav-1, -2, and -3) are a gene family of cytoplasmic membrane-anchored
      scaffolding proteins that: (i) help to sculpt caveolae membranes from the plasma
      membrane proper; and (ii) participate in the sequestration of inactive signaling
      molecules. In the adult, caveolin-1 and -2 are co-expressed and are most abundant
      in type I pneumocytes, endothelia, fibroblastic cells and adipocytes, while the
      expression of caveolin-3 is restricted to striated muscle cells. However, little
      is known regarding the genomic organization and developmental expression of the
      caveolin gene family. Here, using the mouse as a model system, we examine the
      chromosomal localization, the detailed intron-exon organization, and
      developmental expression pattern of the caveolin gene family. cDNAs encoding
      caveolin-1, -2, and -3 were used as probes to isolate murine genomic clones
      containing these genes. Fluorescence in situ hybridization (FISH) analysis using
      these genomic clones as probes reveals that all three caveolin genes are
      localized to murine chromosome 6. Specifically, caveolin-1 and -2 co-localize to
      chromosomal region 6-A2, while caveolin-3 is located within the chromosomal
      region 6-E1. Searches of the NCBI Human/Mouse Homology map indicate that murine
      region 6-A2 corresponds to human chromosome 7q31. As this region (6-A2/7q31) is
      the site of an as yet unidentified tumor suppressor gene(s), our mapping studies
      clearly define caveolin-1 and caveolin-2 as candidate genes that may be deleted
      at these loci. All three caveolin genes show similar intron-exon organization,
      with the last exon of each gene encoding the bulk of the known caveolin
      functional domains. The boundary position of the last exon is essentially
      identical in all three caveolin genes, suggesting that they may have arisen
      through gene duplication events. Developmentally, all three caveolins were
      expressed late during mouse embryogenesis as assessed by Northern and Western
      blot analysis. We examined the localization of the caveolin proteins in sections
      of day 16 mouse embryos using a well-characterized panel of antibody probes.
      Caveolin-1 and -2 were most abundantly expressed in the developing lung
      parenchyma, while caveolin-3 was most abundantly expressed in developing tissues
      that consist primarily of skeletal muscle cells. As the expression of all three
      caveolins in the adult is highest in terminally differentiated cell types, this
      is consistent with the idea that caveolins may be viewed as late markers of
      differentiation during embryogenesis.

PMID- 9662444
TI  - Characterization of a mammalian cDNA encoding a protein with high sequence
      similarity to the Drosophila regulatory protein Rhomboid.
AB  - The Drosophila regulatory protein Rhomboid has been demonstrated genetically to
      facilitate signalling within the Spitz/epidermal growth factor receptor/mitogen
      activated protein kinase pathway. Using a polymerase chain reaction (PCR)-based
      strategy, we have cloned a human cDNA which encodes a protein that has high
      sequence similarity to Rhomboid. The encoded protein, termed rhomboid-related
      protein (RRP), is predicted to contain seven transmembrane domains. Northern
      analysis indicates that RRP mRNA is expressed at highest levels in brain and
      kidney.

PMID- 9662445
TI  - Tryptophan 272: an essential determinant of crystalline cellulose degradation by
      Trichoderma reesei cellobiohydrolase Cel6A.
AB  - Trichoderma reesei cellobiohydrolase Cel6A (formerly CBHII) has a tunnel shaped
      active site with four internal subsites for the glucose units. We have predicted
      an additional ring stacking interaction for a sixth glucose moiety with a
      tryptophan residue (W272) found on the domain surface. Mutagenesis of this
      residue selectively impairs the enzyme function on crystalline cellulose but not
      on soluble or amorphous substrates. Our data shows that W272 forms an additional
      subsite at the entrance of the active site tunnel and suggests it has a
      specialised role in crystalline cellulose degradation, possibly in guiding a
      glucan chain into the tunnel.

PMID- 9662446
TI  - Modification of tissue factor by peroxynitrite influences its procoagulant
      activity.
AB  - Peroxynitrite, a reactive oxidising species resulting from a reaction between
      nitric oxide and the superoxide anion, modifies proteins by nitration of certain
      amino acids such as tyrosine. Tissue factor (TF), a transmembrane protein, is
      expressed on cells under inflammatory conditions and initiates the coagulation
      cascade. The extracellular domain of TF is rich in tyrosine. Exposure of
      recombinant TF and cellular TF to peroxynitrite was associated with a reduction
      in procoagulant activity. This was accompanied by an elevated level of
      nitrotyrosine residues. Peroxynitrite may have a protective role by attenuation
      of the thrombotic properties of TF.

PMID- 9662447
TI  - Cytochrome c release and caspase activation in hydrogen peroxide- and tributyltin
      induced apoptosis.
AB  - The ability of H2O2 and tributyltin (TBT) to trigger pro-caspase activation via
      export of cytochrome c from mitochondria to the cytoplasm was investigated.
      Treatment of Jurkat T lymphocytes with H2O2 resulted in the appearance of
      cytochrome c in the cytosol within 2 h. This was at least 1 h before caspase
      activation was observed. TBT caused cytochrome c release already after 5 min,
      followed by caspase activation within 1 h. Measurement of mitochondrial membrane
      potential (delta psi(m)) showed that both H2O2 and TBT dissipated delta psi(m),
      but with different time courses. TBT caused a concomitant loss of delta psi(m)
      and release of cytochrome c, whereas cytochrome c release and caspase activation
      preceded any apparent delta psi(m) loss in H2O2-treated cells. Thus, our results
      suggest that different mechanisms are involved in triggering cytochrome c release
      with these apoptosis-inducing agents.

PMID- 9662448
TI  - Beta3-adrenergic relaxation of bovine iris sphincter.
AB  - Bovine iris sphincter in vitro responded to beta-adrenergic stimulation with
      pronounced relaxation (EC50 of isoproterenol = 0.3 nM), which was potentiated by
      the cAMP phosphodiesterase inhibitor, isobutylmethylxanthine, and mimicked by the
      adenylyl cyclase activator, forskolin. The beta1/beta2 antagonist, propranolol,
      exhibited low potency with calculated Ki of 200 nM. The beta3-selective
      antagonist, bupranolol, exhibited a biphasic inhibition profile, with calculated
      Kis of approximately 20-50 and 200-300 nM. The beta3-selective agonist, BRL
      37344, elicited 70% of maximal relaxation (EC50 = 30 nM). When relaxation was
      induced by BRL 37344, bupranolol exhibited much higher potency (calculated Ki = 1
      nM). Our data suggest that the beta-adrenergic relaxation response in bovine iris
      sphincter is mediated by a mixed population of beta-adrenergic receptors, with a
      predominant contribution of atypical, most likely beta3 subtype, receptors.

PMID- 9662449
TI  - Human rab11a: transcription, chromosome mapping and effect on the expression
      levels of host GTP-binding proteins.
AB  - Rab11a is a member of the rab-branch of the ras-like small GTP-binding protein
      superfamily that is associated with both constitutive and regulated secretory
      pathways. Using a direct procedure for cDNA cloning of small ras-related GTPases,
      that is based on the screening of eukaryotic cDNA expression libraries using
      [alpha-32P]GTP as a probe, we have isolated two cDNA clones encoding rab11a. Both
      clones share identical coding sequences, but differ in the length and sequence of
      their 3' untranslated regions (3'-UTR). Northern blot hybridisation analysis of
      various human tissues revealed indeed two mRNA species with lengths of 1.0 and
      2.3 kb, respectively. Sequence analysis of the cDNAs identified two different
      putative polyadenylation signals (AATAAA) at positions 927 and 2302 of the larger
      transcript. In addition, the 3'-UTR of the larger transcript exhibited several AU
      rich elements (ARE) that are believed to control gene expression by regulating
      the rate of mRNA degradation. Southern blots of human DNA digested with several
      rare restriction enzymes, and separated by pulse-field gel electrophoresis,
      yielded the same macro-restriction fragment pattern when hybridised with probes
      that discriminate between the two transcripts. Taken together, these findings
      imply that the two mRNA species originate from a single gene, which we have
      mapped to 15q21.3-q22.31, by the use of different polyadenylation sites. As
      expected, both rab11a-cDNAs yielded the same protein product when transiently
      expressed in COS-1 cells, and surprisingly, upregulated the proteome expression
      profile (de novo synthesis or posttranslational modification of preexisting
      proteins) of a few other, yet unknown GTP-binding proteins.

PMID- 9662450
TI  - An essential role of NFkappaB in tyrosine kinase signaling of p38 MAP kinase
      regulation of myocardial adaptation to ischemia.
AB  - We have recently demonstrated that myocardial adaptation to ischemia triggers a
      tyrosine kinase regulated signaling pathway leading to the translocation and
      activation of p38 MAP kinase and MAPKAP kinase 2. Since oxidative stress is
      developed during ischemic adaptation and since free radicals have recently been
      shown to function as an intracellular signaling agent leading to the activation
      of nuclear transcription factor, NFkappaB, we examined whether NFkappaB was
      involved in the ischemic adaptation process. Isolated perfused rat hearts were
      adapted to ischemic stress by repeated ischemia and reperfusion. Hearts were
      pretreated with genistein to block tyrosine kinase while SB 203580 was used to
      inhibit p38 MAP kinases. Ischemic adaptation was associated with the nuclear
      translocation and activation of NFkappaB which was significantly blocked by both
      genistein and SB 203580. The ischemically adapted hearts were more resistant to
      ischemic reperfusion injury as evidenced by better function recovery and less
      tissue injury during post-ischemic reperfusion. Ischemic adaptation developed
      oxidative stress which was reflected by increased malonaldehyde formation. A
      synthetic peptide containing a cell membrane-permeable motif and nuclear
      sequence, SN 50, which blocked nuclear translocation of NFkappaB during ischemic
      adaptation, significantly inhibited the beneficial effects of adaptation on
      functional recovery and tissue injury. In concert, SN 50 reduced the oxidative
      stress developed in the adapted myocardium. These results demonstrate that p38
      MAP kinase might be upstream of NFkappaB which plays a role in ischemic
      preconditioning of heart.

PMID- 9662451
TI  - A cysteine-11 to serine mutant of G alpha12 impairs activation through the
      thrombin receptor.
AB  - We have recently reported that G alpha12 is acylated with palmitic acid [Veit et
      al., FEBS Lett. 339 (1994) 160-164]. Here we identify cysteine 11 as the sole
      palmitoylation site and assess the function of G alpha12 palmitoylation after
      expression of wild type and acylation-deficient mutant in insect cells. Our
      experimental approach yielded the following results. (1) Palmitoylation of G
      alpha12 has no influence on the subunit interactions. (2) Palmitoylation promotes
      membrane binding of G alpha12 when this protein is expressed alone. Membrane
      attachment of the heterotrimer occurs independent of the presence of fatty acids
      in G alpha12. (3) Assays for agonist-stimulated binding of [35S]GTPgammaS after
      expression of the human thrombin receptor (PAR1) along with G alpha12 and the
      betagamma subunits revealed a 70% inhibition with the palmitoyl-deficient mutant.

PMID- 9662452
TI  - Pore accessibility during C-type inactivation in Shaker K+ channels.
AB  - Shaker K+ channels inactivate through two distinct molecular mechanisms: N-type,
      which involves the N-terminal domain and C-type that appears to involve
      structural modifications at the external mouth of the channel. We have tested
      pore accessibility of the Shaker K+ channel during C-type inactivation using Ba2+
      as a probe. We determined that external Ba2+ binds to C-type inactivated channels
      forming an extremely stable complex; i.e. there is Ba2+ trapping by C-type
      inactivated channels. The structural changes Shaker channels undergo during C
      type inactivation create high energy barriers that hinder Ba2+ exit to either the
      extracellular solution or to the intracellular solution.

PMID- 9662453
TI  - Site directed mutants of Noxiustoxin reveal specific interactions with potassium
      channels.
AB  - Several site directed mutations were introduced into a synthetic Noxiustoxin
      (NTX) gene. Alanine scanning of the nonapeptide at the N-terminal segment of NTX
      (threonine 1 (T1) to serine 9 (S9)) was constructed and the recombinant products
      were obtained in pure form. Additionally, lysine 28 (K28) was changed to arginine
      (R) or glutamic acid (E), cysteine 29 was changed to alanine, and residues 37-39
      (Tyr-Asn-Asn) of the carboxyl end were deleted. The recombinant mutants were
      tested for their ability to displace 125I-NTX from rat brain synaptosome
      membranes, as well as for their efficiency in blocking the activity of Kv1.1 K+
      channels expressed in Xenopus laevis oocytes. The main results indicate that
      residues K6, T8 at the amino end, and K28 and the tripeptide YNN at the carboxyl
      end are involved in specific interactions of NTX with rat brain and/or Kv1.1 K+
      channels.

PMID- 9662454
TI  - Structural elements of Trimeresurus flavoviridis serum inhibitors for recognition
      of its venom phospholipase A2 isozymes.
AB  - Five inhibitors (PLI-I-V) against Trimeresurus flavoviridis (Tf, habu snake,
      Crotalinae) venom phospholipase A2 (PLA2) isozymes have been isolated from its
      serum. PLI-I, which is composed of two repeated three-finger motifs, and PLI-IV
      and PLI-V, which contain a sequence similar to the carbohydrate recognition
      domain (CRD) of C-type lectins, were expressed in the forms fused with
      glutathione S-transferase (GST). The resulting GST-PLIs showed ability to bind to
      three Tf venom PLA2 isozymes. The binding study with the truncated forms
      indicated that one of two three-finger motifs of PLI-I was able to bind to PLA2
      isozymes. The N-terminal 37-amino acid fragment and the CRD-like domain of PLI-IV
      and PLI-V were bound to PLA2 isozymes. On the other hand, their C-terminal 12
      amino acid segment also associated with PLA2 isozymes. When either of two units
      of a hydrophobic tripeptide in this sequence was replaced by trialanine, the
      binding was completely abolished, indicating that the C-terminal hydrophobic
      cores of PLI-IV and PLI-V were critically responsible for the binding to venom
      PLA2 isozymes.

PMID- 9662455
TI  - Expression of functionally active ATP-sensitive K-channels in insect cells using
      baculovirus.
AB  - We have expressed active ATP-sensitive K-channels (K(ATP) channels) in Spodoptera
      frugiperda (Sf9) cells using a baculovirus vector. A high yield of active
      channels was obtained on co-infection with SUR1 and Kir6.2 engineered to contain
      N- and/or C-terminal tags to permit detection by Western blotting. Channel
      activity was sensitive to ATP, glibenclamide and diazoxide. Channel activity was
      also obtained on expression of a C-terminally truncated Kir6.2 (Kir6.2 deltaC26):
      these channels were blocked by ATP but were insensitive to sulphonylureas. In
      contrast to Xenopus oocytes and mammalian cells the full length Kir6.2 also gave
      rise to active channels in Sf9 cells when expressed alone. The highest yield of
      active K(ATP) channels was obtained on infection with a fusion protein containing
      SUR1 linked to Kir6.2 deltaC26 via a 6-amino acid linker.

PMID- 9662456
TI  - Hyperleptinaemia in mice induced by administration of the tyrosine hydroxylase
      inhibitor alpha-methyl-p-tyrosine.
AB  - Alpha-methyl-p-tyrosine (alphaMPT), an inhibitor of tyrosine hydroxylase, was
      administered to mice to block noradrenaline synthesis. Ten hours after injection
      of alphaMPT there was a 6-fold increase in plasma leptin. The level of ob mRNA in
      epididymal white adipose tissue was also increased, but UCP1 mRNA in brown fat
      fell. In contrast to lean mice, ob mRNA in white fat of ob/ob mice was not
      increased by alphaMPT. AlphaMPT raised plasma leptin in fasted as well as fed
      mice. Hyperleptinaemia was attenuated by treatment with a beta3-adrenoceptor
      agonist. Inhibition of noradrenaline synthesis leads to the rapid induction of
      hyperleptinaemia; it is suggested that sympathetic tone plays a pivotal role in
      regulating leptin production.

PMID- 9662457
TI  - Posttranslational modifications of trichomonad tubulins; identification of
      multiple glutamylation sites.
AB  - The alpha- and beta-tubulins present in cytoskeletons of Tritrichomonas
      mobilensis are extensively glutamylated. Automated sequencing and mass
      spectrometry of the carboxyterminal peptides identifies 4 glutamylation sites in
      alpha- and 2 sites in beta-tubulin. They are marked by asterisks in the terminal
      sequences GDE*E*E*E*DDG (alpha) and EGE*E*DEEAEA (beta). This is the first report
      that tubulin glutamylation can occur at multiple sites. Although T. mobilensis
      has four flagellae the tubulins lack polyglycylation. Thus glycylation is not
      necessary for formation or function of axonemal microtubules. Alpha-tubulin is
      completely acetylated at lysine 40 and shows no tyrosine cycle. Peptide sequences
      establish two distinct beta-tubulins.

PMID- 9662458
TI  - AtPUMP: an Arabidopsis gene encoding a plant uncoupling mitochondrial protein.
AB  - A cDNA clone (AtPUMP) encoding a plant uncoupling mitochondrial protein was
      isolated from Arabidopsis thaliana. The cDNA contains an open reading frame of
      921 nucleotides encoding 306 amino acids (predicted molecular weight 32,708). The
      predicted polypeptide is 81% identical and 89% similar to the potato UCP-like
      protein, and includes an energy transfer protein motif common to mitochondrial
      transporters. The AtPUMP gene exists as a single copy in the Arabidopsis genome.
      The corresponding transcript was expressed in all tissues and was strongly
      induced by cold treatment. We suggest that the putative AtPUMP protein may play a
      role in heat-requiring physiological events in Arabidopsis.

PMID- 9662459
TI  - Molecular cloning of a novel GTP-binding protein induced in fish cells by
      rhabdovirus infection.
AB  - We have cloned and sequenced a cDNA encoding GTP-binding protein from a fish
      cell, CHSE-214. The clone was 1493 bp long and contained an open reading frame
      encoding 364 amino acids. It has the five sequence motifs G1-G5 that are
      conserved in all GTP-binding proteins. Its amino acid sequences are strikingly
      different from those of the well-characterized G-proteins. However, sequences
      closely related to this protein are found in various kinds of species including
      human, Arabidopsis, Drosophila and archaebacteria, suggesting a novel subfamily
      within the superfamily of the GTP-binding proteins. Northern analysis indicates
      that this gene is constitutively expressed at a low level in normal cells but is
      induced by fish rhabdovirus infection at about 24 h post infection and disappears
      thereafter. Based on these observations, we propose that this protein represents
      an evolutionarily conserved novel subfamily of GTP-binding proteins which may
      play an important role in fish rhabdovirus infection.

PMID- 9662460
TI  - Regulation of the type II oncostatin M receptor expression in lung-derived
      epithelial cells.
AB  - Oncostatin M (OSM) is a potent modulator of human lung-derived epithelial cell
      function. This cytokine binds two distinct receptor complexes: type I OSM
      receptor which is also a functional receptor for leukemia inhibitory factor
      (LIF), and type II OSM-specific receptor. The role of these two distinct
      receptors in mediating the response of individual cell types to OSM has not been
      delineated. In contrast to LIF, OSM induces synthesis of alpha1-antichymotrypsin
      and alpha1-antiproteinase inhibitor in lung-derived epithelial cells. The
      differential responsiveness to LIF and OSM suggested that the response of lung
      epithelial cells to OSM may be mediated by the OSM-specific receptor. Therefore,
      we characterized lung-derived epithelial cells for the expression of type II OSM
      receptor mRNAs, and the regulation of the mRNAs encoding the components of the
      OSM-specific receptor by cytokines and dexamethasone.

PMID- 9662461
TI  - Mutational analysis of Glu272 in elongation factor 1A of E. coli.
AB  - In our previous work (Mansilla et al. (1997) Protein Eng. 10, 927-934) we showed
      that Arg7 of Escherichia coli elongation factor Tu (EF1A) plays an essential role
      in aminoacyl-tRNA (aa-tRNA) binding. Substitution of Arg7 by Ala or Glu lost this
      activity. We proposed that Arg7 forms a salt bridge with the charged conserved
      amino acid Glu272 (Asp284 in Thermus aquaticus) thereby binding the N-terminal
      region of the protein to domain 2 and thus completing the conformational
      rearrangement needed for binding aa-tRNA. In this work we have mutated Glu272 to
      arginine, either alone (Glu272Arg), or in combination with one of the above
      mentioned mutations (Arg7Glu/Glu272Arg) in order to test this hypothesis. Our
      results show that, in confirmation of our thesis based on structural knowledge,
      the substitution of Glu272 (Asp284) decreases the ability of EF1A:GTP to bind aa
      tRNA.

PMID- 9662462
TI  - A peptide derived from the N-terminal region of HIV-1 Vpr promotes nuclear import
      in permeabilized cells: elucidation of the NLS region of the Vpr.
AB  - Viral protein r (Vpr), a HIV-1 auxiliary protein which mediates nuclear import of
      the viral preintegration complex (PIC), contains two regions, N- and C-terminal,
      which have been proposed to function as a nuclear localization signal (NLS). We
      have synthesized peptides corresponding to both regions (designated as VprN and
      VprC), conjugated them to bovine serum albumin (BSA), and tested their ability to
      mediate nuclear import in permeabilized cells. Only VprN, and not VprC,
      functioned as an active NLS and promoted translocation of the conjugate into
      nuclei. Nuclear import of the conjugate was found to be energy and temperature
      dependent and was inhibited by wheat germ agglutinin (WGA). However, it did not
      require the addition of cytosolic factors and was not inhibited by the prototypic
      SV40 large T-antigen NLS peptide. Our results show that Vpr harbours a non
      conventional negatively charged NLS and therefore suggest that Vpr may use a
      distinct nuclear import pathway.

PMID- 9662463
TI  - Potential applications of antithrombin concentrate in system inflammatory
      disorders. Introduction.

PMID- 9662464
TI  - Effects of viral activation of the vessel wall on inflammation and thrombosis.
AB  - Herpes simplex virus type 1 and cytomegalovirus alter the phenotype of the
      endothelium in vitro from anticoagulant to procoagulant, thereby promoting the
      adherence of neutrophils and platelets to the endothelium. Virus infection of the
      endothelium induces the expression of viral glycoproteins and adhesion molecules,
      which promote neutrophil and monocyte adhesion. Herpes simplex infection of the
      endothelium promotes prothrombinase assembly, allowing more efficient thrombin
      generation. Excess thrombin generation causes translocation of P-selectin. Viral
      infection also induces the procoagulant molecule, tissue factor, in endothelial
      cells. These enhanced procoagulant effects are associated with the loss of
      anticoagulants, including thrombomodulin, prostacyclin and tissue plasminogen
      activator. These studies support the speculation that virus infection in vivo
      promotes vascular injury and thrombosis, which may contribute to disease states
      such as atherosclerosis.

PMID- 9662465
TI  - Antithrombin and ischemia/reperfusion.
AB  - Acute inflammation, a localized response that occurs in various diseases, is
      characterized by neutrophil infiltration into tissues. This process requires
      neutrophils to initially tether and roll along the endothelium of postcapillary
      venules before undergoing firm adhesion and emigration out of the vasculature
      into the tissues. Recently, thrombin has been implicated at multiple sites in the
      inflammatory cascade, and may represent an important link between inflammation
      and thrombosis. Our recent studies demonstrate that thrombin is an important
      mediator of neutrophil-dependent injury in ischemia-reperfusion injury.
      Furthermore, antithrombin concentrate may be therapeutically efficacious in
      ischemia-reperfusion injury, as it is capable of attenuating the thrombin
      mediated effects on neutrophil-endothelial interactions.

PMID- 9662466
TI  - Endothelial and leukocyte adhesion molecules in inflammation and disease.
AB  - Injury associated with ischemia and reperfusion is a significant factor in a
      number of clinical diseases. We have completed a number of preclinical studies
      investigating the blockade of leukocyte adhesion molecules in ischemia
      reperfusion injury. In our work and in the work of other investigators,
      monoclonal antibodies directed to CD18, P-selectin and L-selectin were effective
      in reducing ischemia-reperfusion injury to the rabbit ear and in reducing injury
      following hemorrhagic shock in both rabbits and nonhuman primates. Ischemia
      reperfusion injury was also reduced by synthetic oligosaccharide sLe(x). These
      studies suggest that adhesion blockade might be effective in the clinical
      setting.

PMID- 9662467
TI  - Antithrombin prevents endotoxin-induced pulmonary vascular injury by inhibiting
      leukocyte activation.
AB  - Replacement of antithrombin has proved to be effective for treating disseminated
      intravascular coagulation. The administration of antithrombin is also useful for
      preventing organ failure in animals challenged with endotoxin or bacteria, and it
      increases the survival rate of such animals. Since inhibition of coagulation
      abnormalities by heparin failed to prevent organ failure in animals challenged
      with bacteria, antithrombin might exert therapeutic effects independently of its
      anticoagulant effect. These therapeutic mechanisms of antithrombin have been
      explored by using animal models of septicemia. Antithrombin prevents pulmonary
      vascular injury by inhibiting leukocyte activation in rats challenged with
      endotoxin. A higher dose of antithrombin was required to prevent pulmonary
      vascular injury than was required to inhibit disseminated intravascular
      coagulation. This preventive effect of antithrombin is mediated by the promotion
      of endothelial release of prostacyclin, an inhibitor of leukocyte activation. An
      interaction between antithrombin and heparin-like glycosaminoglycans on the
      endothelial cell surface appears to be important for this effect. Heparin
      inhibits such therapeutic effects of antithrombin by preventing it from
      interacting with the cell surface heparin-like glycosaminoglycans. Since
      activated leukocytes are of critical importance in patients with sepsis
      associated organ failure, this anti-inflammatory activity of antithrombin may
      explain why it can prevent organ failure as well as coagulation abnormalities in
      patients with sepsis.

PMID- 9662468
TI  - Therapeutic applications of antithrombin concentrates in systemic inflammatory
      disorders.
AB  - During severe sepsis, the sustained consumption and/or inhibition of antithrombin
      leads to a prolonged procoagulant state, which indicates that the administration
      of antithrombin may be useful in this condition. Animal studies have shown that
      high doses of antithrombin concentrates can prevent disseminated intravascular
      coagulation and death. In humans, high doses of antithrombin are required to
      maintain supranormal antithrombin levels and overcome the magnitude of
      antithrombin consumption. Three placebo-controlled, double-blind studies of
      antithrombin concentrates have been performed in France, Germany and northwestern
      Europe. A meta-analysis of these three studies showed a nonsignificant 22%
      reduction in 30-day, all-cause mortality. A multicenter phase III trial is needed
      to demonstrate that antithrombin administration can reduce mortality in septic
      patients.

PMID- 9662469
TI  - Prospects for the genetic transformation of arthropods.

PMID- 9662470
TI  - Pantropic retroviral vectors mediate somatic cell transformation and expression
      of foreign genes in dipteran insects.
AB  - The control of insects that transmit disease and damage crops has become
      increasingly difficult. The ability to genetically engineer insects would
      facilitate strategies to protect crops and block arthropod vector-borne disease
      transmission. Transformation vectors based on insect transposable elements have
      been developed, but most have limited host ranges. A promising alternative is the
      pantropic retroviral vector, which is packaged with the envelope glycoprotein
      from vesicular stomatitis virus and is replication-defective. We show here that
      pantropic murine retroviral vectors can mediate high-level expression of foreign
      genes in somatically transformed insect larvae and adults of three dipteran
      genera. This success demonstrates the potential for germline transformation
      mediated by pantropic retroviral vectors.

PMID- 9662471
TI  - Cloning of the V-ATPase B subunit cDNA from Culex quinquefasciatus and expression
      of the B and C subunits in mosquitoes.
AB  - The V-ATPase B subunit cDNA isolated from the midgut and Malpighian tubules of
      Culex quinquefasciatus larvae has a 1476 bp ORF encoding a 492 amino acids
      protein with a predicted mass of 54.8 kDa. Northern blot analysis reveals the
      presence of 1.8 and 4.2 kb transcripts in larvae and a 3.0 kb transcript in
      pupae. A single 57 kDa protein band is detected in immunoblot analysis of protein
      extracts from C. quinquefasciatus and A. aegypti larvae. Using antibodies to the
      B subunits we demonstrate high-level expression of these subunits in ion
      transporting cells of caeca and anterior midgut, and in Malpighian tubules and
      rectum. High V-ATPase expression was also observed in the larval salivary glands,
      central nervous system neurophile, the thoracic endocrine complex and in imaginal
      discs.

PMID- 9662472
TI  - Chitinases are a multi-gene family in Aedes, Anopheles and Drosophila.
AB  - Degenerate primers were used to amplify by the polymerase chain reaction (PCR)
      DNA fragments from the chitinase genes of five insect species: Aedes aegypti,
      Anopheles freeborni, Anopheles gambiae, Anopheles stephensi and Drosophila
      melanogaster. As many as four different products were found for each species;
      each deduced protein sequence having greatest homology to chitinase sequences
      from other species of insects and the crustacean, Penaeus japonicus. The four PCR
      products of A. aegypti hybridize to two loci, with three of the products derived
      from either three tightly linked genes or a single gene with three catalytic
      domains. Southern blot hybridizations of the PCR products from the species of
      Anopheles suggest a similar arrangement.

PMID- 9662473
TI  - Excisions of the Ikirara1 transposon in an Anopheles gambiae cell line.
AB  - In order to determine whether there are active genomic copies of the Anopheles
      gambiae transposon Ikirara, we developed an excision assay based on an internally
      deleted copy, Ikirara1. This element has 216 bp perfect inverted repeats at its
      termini, apparently caused a duplication of the dinucleotide TA at its insertion
      site between vitellogenin genes, and is thought to have been inserted recently at
      this location. The firefly luciferase gene on the E. coli tac promoter was
      inserted into Ikirara1 and used as a reporter to assess whether activities in an
      A. gambiae cell line could cause Ikirara excision. Excisions were observed at a
      rate of 0.038% in these experiments, but none was detected in controls. The five
      independent excision products examined gave identical sequences. Excisions were
      nearly precise, but left behind a footprint of 15 bp of the 3' inverted repeat of
      Ikirara1 between duplicated TAs. These excisions can be explained by a mechanism
      formally similar to that proposed for excision of mariner/Tc1 elements with cuts
      at the transposon ends staggered by 15 bases.

PMID- 9662474
TI  - Microsatellite sequences are under-represented in two mite genomes.
AB  - Microsatellites are known to be a common feature of eukaryote genomes. Here we
      investigate the presence of microsatellite sequences in the genome of two mite
      species, Tetranychus urticae and Amblyseius fallacis, based on screening of both
      mite genomic libraries and Southern blots of these mites that we compare to two
      vertebrates. No signal with GT15 or a faint smear with CT10 were obtained in
      Southern analysis for the two mites, whereas both probes strongly bound with
      vertebrate DNA. Genomic libraries constructed in plasmid and lambda vectors were
      probed and only two CT microsatellites were isolated for T. urticae. Among eight
      trinucleotides probes tested, the strongest hybridization signal was detected for
      T. urticae with CAT and TGA probes. These two classes of repeats were also the
      most represented in genomic library screenings. However, only sequences with
      short numbers of units could be detected (<CAT4 or TGA9). Congruency of Southern
      analysis and screening of partial genomic libraries indicates an under
      representation of microsatellite sequences in the two mite genomes. The potential
      of the scarce repetitive DNA isolated from mites to serve as population genetics
      markers is discussed on the basis of preliminary assessment of their
      polymorphism.

PMID- 9662475
TI  - A lysozyme in the salivary glands of the malaria vector Anopheles darlingi.
AB  - A cDNA encoding a lysozyme expressed specifically in the salivary glands of the
      malaria vector mosquito, Anopheles darlingi, was isolated by differential
      screening an adult female salivary gland library with abdomen and salivary gland
      cDNAs. The primary nucleic acid sequence of the cDNA contains a deduced coding
      region of 429 nucleotides and 5'- and 3'-end non-transcribed regions. A signal
      peptide of twenty-three amino acids and a mature protein of 120 amino acids are
      evident in the conceptual translation product. The results of RT-PCR experiments
      indicated that in adult mosquitoes this gene is expressed specifically in the
      salivary glands. Lysozyme enzymatic activity was detected in the salivary glands
      and abdomens of adult mosquitoes, but the pH optimum differed for each tissue and
      this was interpreted to indicate the presence of more than one enzyme, each being
      expressed in a different tissue. The salivary gland lysozyme may be involved in
      protection against bacterial infection in the anterior portion of the mosquito
      digestive tract.

PMID- 9662476
TI  - Polydnavirus-mediated inhibition of lysozyme gene expression and the
      antibacterial response.
AB  - Parasitism of lepidopteran host larvae by hymenopteran parasitoids impairs the
      cellular immune response via expression of polydnavirus genes. Encapsulation of
      parasitoid eggs is thereby prevented. Parasitized insects are susceptible to
      opportunistic infections, suggesting that additional components of the immune
      system are affected. Insects normally respond to infection by inducing the
      synthesis of an array of antibacterial factors, including cecropins and lysozyme
      via a NFkappaB/lkappaB-like signal transduction pathway. To characterize the
      effects of PDVs on the antibacterial immune response, plasma antibacterial
      activities were assayed in H. virescens larvae infected with the C. sonorensis
      PDV. Plasma lysozyme activity in Heliothis virescens was reduced in parasitized
      and PDV-infected larvae after immune challenge. To examine the regulation of
      lysozyme after CsPDV injection, the Heliothis virescens lysozyme cDNA was cloned.
      In contrast to plasma lysozyme activity, the 1.1 kb lysozyme mRNA was induced in
      fat body and haemocytes by known elicitors. The data suggest that CsPDV, like
      some other viruses, regulates host cell gene expression at the level of
      translation. We propose that the immunodeficiencies caused by CsPDV injection are
      caused, in part, by the targeted translational inhibition of specific humoral
      immune response transcripts.

PMID- 9662477
TI  - Hpall endonuclease distinguishes between two species in the Anopheles funestus
      group.
AB  - The Anopheles funestus group consists of at least eight species that are
      currently identified mainly on morphological criteria. Until recently, only An.
      funestus s.s. was implicated in the transmission of malaria in Africa, but recent
      work in Tanzania has shown that An. rivulorum is also involved, albeit to a
      lesser degree than An. funestus. The constraints in the identification of the
      species and the need to clarify better their epidemiological role have led to the
      development of a PCR-RFLP method for the identification of two anthropophilic
      members of the group. Using PCR primers developed from the D3 region in the 28S
      ribosomal gene, amplified products were digested with the restriction
      endonuclease Hpall. This produced two distinct fragments on an agarose gel that
      could be used to separate An. funestus from An. vaneedeni. The technique needs to
      be tested on natural populations of these two species as well as on other members
      of the An. funestus group.

PMID- 9662478
TI  - The heat shock 70 gene family in the Mediterranean fruit fly Ceratitis capitata.
AB  - The cloning and the characterization of the heat shock 70 (hsp70) genes of the
      medfly C. capitata, a major agricultural pest, are presented. Six genomic clones
      were isolated by screening a medfly genomic library with an hsp70 genomic
      fragment of Drosophila melanogaster. They form two 30 kb contigs, both of which
      map cytogenetically in a single major heat shock puff (3L:24C) of the salivary
      gland polytene chromosomes. Restriction mapping and blot hybridization indicated
      the presence of six putative hsp70 genes in these two closely linked regions. The
      sequence of one of these genes suggests that it is a heat-inducible hsp70 gene.
      The 638-codon open reading frame shows 84% identity at the amino acid level
      (73.5% at the nucleotide level), relative to corresponding D. melanogaster
      sequences. The 5' untranslated leader sequence, approximately 200 bp long, is not
      interrupted by introns and is very rich (48%) in adenine residues, resembling
      Drosophila heat-inducible hsp70 genes. Furthermore, the promoter of this gene
      contains two characteristic heat shock elements close upstream from the TATA box.
      The levels of the hsp70 transcripts are very low at 25-30 degrees C, increase
      significantly at 33 degrees C and reach maximum at 39 degrees C.

PMID- 9662479
TI  - Structure and associated mutational effects of the cysteine proteinase (CP1) gene
      of Drosophila melanogaster.
AB  - The complete structure of the cysteine proteinase (CP1) gene reveals two large 5'
      introns as well as a small third intron. Deletion studies have shown that null
      mutations for the locus are female sterile with partial male sterility as well as
      wing and pigmentation effects. Null alleles can be produced by either deletions
      to the left or deletions to the right of a P element insertion in the long second
      intron of the gene. A nearby phenylalanyl tRNA synthetase gene (Pts) was also
      identified.

PMID- 9662480
TI  - Polymorphisms and fluctuations in copy number of amplified esterase genes in
      Culex pipiens mosquitoes.
AB  - In Culex pipiens mosquitoes, A2 esterase alleles are co-amplified with B2
      esterase alleles in response to selection with organophosphate insecticides. In
      this study the amplified A2 and B2 sequences were compared between twelve strains
      from four continents by restriction mapping. The restriction maps were almost
      identical in each strain throughout 22 kb surrounding the genes, suggesting that
      this represents a constant core sequence. A polymorphism was found in two strains
      collected from Egypt and Kenya in the mid 1980s. This polymorphism was present in
      all copies of the amplicon, which suggests that a mechanism of sequence
      homogenization was operating, i.e. concerted evolution. These two strains were
      almost certainly descendants from the same population and migration probably
      occurred along the River Nile. Although the maps were almost identical in each
      strain, dot blotting demonstrated that amplification levels differed by up to 13
      fold between strains. Thus the presence of the A2-B2 haplotype cannot be used to
      indicate the level of amplification or any particular degree of resistance.

PMID- 9662481
TI  - Clinical and therapeutic significance of the Na+,K+ pump*.
AB  - 1. The Na+,K+-ATPase or Na+,K+-pump, mediating the active transport of Na+ and
      K+, which was first identified 40 years ago, is a central target for acute and
      long-term regulation, as well as for therapeutic intervention. Acute stimulation
      of the Na+,K+-pump in skeletal muscle by insulin, catecholamines, beta2-agonists
      or theophylline increases the intracellular uptake of K+ and accounts for the
      hypokalaemia elicited by these agents. Conversely, digitalis intoxication elicits
      hyperkalaemia via acute inhibition of the Na+, K+-pump. 2. Simple and accurate
      methods have been developed for the quantification of the total concentration of
      Na+,K+-pumps in small (0.5-5 mg) fresh or frozen biopsies of human skeletal
      muscle, myocardium or other tissues. This has allowed the identification of
      several long-term regulatory changes in the concentration of this transport
      system in human tissues. In skeletal muscle, upregulation is induced by training,
      thyroid hormones or glucocorticoids. Downregulation is seen in hypothyroidism,
      cardiac insufficiency, myotonic dystrophy, McArdle disease, K+ deficiency and
      after muscle inactivity. 3. Since the skeletal muscles contain one of the major
      pools of Na+,K+-pumps, these changes are important for the ability to
      counterregulate the hyperkalaemia elicited by exercise or the ingestion of K+.
      Moreover, downregulation or inhibition of the Na+, K+-pumps in skeletal muscle
      interferes with contractile performance. Since digitalis glycosides bind to the
      Na+,K+-pump, the muscles constitute a large distribution volume for these agents
      and are therefore an important determinant for their plasma level. 4. In cardiac
      insufficiency, the decrease in the concentration of Na+, K+-pumps in the
      myocardium is over a wide range correlated to the concomitant reduction in
      ejection fraction. The regulatory and pathophysiological changes in the activity
      and concentration of Na+, K+-pumps are important for the contractile function of
      skeletal muscle and heart as well as for K+ homoeostasis and the response to
      digitalization.

PMID- 9662482
TI  - Role of T-cells in the development of arthritis.
AB  - 1. Arthritis can be induced in rodents by priming T-cells to respond to a foreign
      antigen and then challenging with antigen intra-articularly. This may be a model
      of the situation in human reactive arthritis in which T-cell responses are
      induced by antigens from organisms which trigger reactive arthritis (e.g.
      Chlamydia trachomatis) and antigen finds its way to the joint, most probably
      within macrophages. Priming by previous exposure to antigens similar to those of
      the triggering organism could also play a part in pathogenesis. Genetic factors
      determining the nature and control of the immune response affect the severity and
      duration of the arthritis. 2. T-cell-dependent arthritis can be induced in
      rodents by immunization with an antigen known to be expressed in the joint (e.g.
      Type II collagen). Whether this is an important mechanism in human arthritis is
      still unclear, even though diseases such as rheumatoid arthritis are
      conventionally thought of as 'autoimmune'. No convincing candidate autoantigen
      has yet been identified in rheumatoid arthritis, and recent experiments in
      transgenic mice indicate that arthritis can be induced by an autoimmune T-cell
      response which does not target an antigen confined to the joint. 3. Adjuvant
      arthritis is a classical T-cell-dependent animal model of human arthritis;
      recently arthritis has been described as a rare complication in patients
      receiving adjuvant (intra-vesical live BCG organisms) for bladder cancer.
      Increasing attention is being paid to the role of adjuvants as 'danger signals',
      which allow the immune system to determine whether an antigenic challenge poses a
      threat. Inappropriate attachment of danger signals to self antigens may result in
      T-cell-mediated immune responses, which could play a part in the pathogenesis of
      arthritis. 4. Animal studies indicate that autoimmune/inflammatory diseases can
      be produced by imbalances within T-cell populations, and that certain T-cells
      also have the capacity to regulate inflammatory responses. Among the latter are T
      cells specific for conserved epitopes within heat shock protein 60. The extent to
      which T-cells of this kind operate in human disease has yet to be determined.

PMID- 9662483
TI  - Heart rate control of blood pressure variability in children: a study in subjects
      with fixed ventricular pacemaker rhythm.
AB  - 1. To investigate the influence of heart rate variability on blood pressure
      variability, short-term variability in heart rate and blood pressure was studied
      in 10 children with fixed ventricular pacemaker rhythm (80 beats/min). Ten
      healthy children, in sinus rhythm, served as a reference population. 2. Arterial
      blood pressure and heart rate were measured continuously using a finger arterial
      device and an ECG respectively. Power spectra for heart rate and blood pressure
      (systolic and diastolic) were calculated in both supine and orthostatic
      positions. In addition, acute changes in blood pressure and heart rate during
      active standing were studied. 3. Healthy children exhibited considerable heart
      rate variability, which was slightly more pronounced in the supine position,
      while children with a fixed ventricular rate had no heart rate variability in
      either position. 4. Despite the differences in heart rate variability, mean
      systolic blood pressure and its variability profiles were poorly affected by the
      suppression of heart rate variability. The lack of autonomic control on the sinus
      node was associated with a reduction in magnitude of the changes in systolic
      blood pressure variability induced by orthostatic posture. 5. The suppression of
      heart rate fluctuations induced a noticeable decrease in diastolic blood pressure
      fluctuations, which was most conspicuous in the children with fixed cardiac
      rhythm when in the supine position. This may be explained by the lack of
      diastolic blood pressure fluctuations, physiologically due to heart rate
      fluctuations through the run-off effect: the longer the cardiac cycle, the
      greater the diastolic pressure decay. These results may challenge the classical
      theory of baroreflex-mediated diastolic blood pressure control described in adult
      patients. 6. During active standing, the early drop in systolic blood pressure
      was greater in subjects with fixed ventricular rhythm. A rise in heart rate of 36
      beats/min was observed in the healthy subjects in response to active standing. 7.
      We conclude that in normal children, heart rate fluctuations increase the blood
      pressure variability rather than buffering it. However, during acute orthostatic
      stress, the abrupt baroreflex-mediated heart rate rise may partly compensate for
      the reduction in blood pressure.

PMID- 9662484
TI  - Autonomic modulation of heart rate and blood pressure in hypertensive subjects
      with symptoms of anxiety.
AB  - 1. The influence of anxiety symptoms on autonomic nervous system cardiovascular
      control has never been studied in hypertensive subjects. This study was designed
      to verify the presence of sympathetic hyperactivity in hypertension associated
      with anxiety symptoms. 2. Neuroautonomic cardiovascular control was evaluated
      using short-time power spectral analysis of RR and arterial pressure variability
      at baseline and after the head-up tilt test. The two spectral components
      principally influenced by the autonomic nervous system are the low-frequency (LF)
      component, mainly though not exclusively due to sympathetic modulation, and the
      high-frequency (HF) component, due to parasympathetic activity. The ratio of LF
      to HF powers (LF:HF) provides an index of the sympathovagal sinus balance. 3. We
      studied 33 hypertensive subjects (mean age 47+/-1 years; M:F=19:14) and 37
      normotensive control subjects (mean age: 47+/-2 years; M:F=20:17) divided into
      four subgroups: hypertensive subjects who scored 2 or more on a 5-item anxiety
      symptom scale, hypertensive subjects who scored 0, normotensive controls who
      scored 2 or more and normotensive controls who scored 0. LF:HF and LF during rest
      were significantly higher (P<0.05) in hypertensive and normotensive groups with
      an anxiety score of 2 or more compared with the two groups who scored 0. HF of
      systolic blood pressure was significantly lower in the hypertensive group who
      scored 2 or more than in the hypertensive group who scored 0 (P<0.05). Tilt in
      both hypertensive groups reporting anxiety symptoms left the indexes of
      sympathetic modulation unchanged. Tilt in hypertensive subjects reporting anxiety
      symptoms also induced a significant fall in arterial pressure (P<0.05). The mean
      left ventricular mass index was significantly higher in the hypertensive subjects
      who had anxiety scores of 2 or more than in those scoring 0 (144.7+/-3.0 versus
      133. 4+/-2.31, P<0.05). 4. In conclusion, normotensive and hypertensive subjects
      reporting anxiety symptoms showed increased sympathetic modulation of heart rate
      at rest. Higher anxiety scores seem to be associated with the development of left
      ventricular hypertrophy.

PMID- 9662485
TI  - Serum total sialic acid, a reputed cardiovascular risk factor, and its
      relationship to lipids, plasma fasting insulin, blood pressure and body mass
      index in normal individuals.
AB  - 1. Serum sialic acid is a reputed cardiovascular risk factor, but the reason why
      this is so is not clear. We therefore studied its relationship with other known
      cardiovascular risk factors (particularly those associated with insulin
      resistance) in 100 healthy young subjects (54 females and 46 males, age 20.7+/
      0.89 years). 2. There was a significant univariate correlation between serum
      total sialic acid and fasting plasma insulin. Serum total sialic acid also
      correlated with fasting plasma glucose concentration and serum cholesterol and
      triacylglycerol. 3. In females there was a strong univariate correlation between
      serum total sialic acid and plasma fasting insulin and glucose concentrations,
      although in males there was a weaker univariate correlation between serum total
      sialic acid and fasting plasma glucose and the insulin resistance index. In
      addition, serum total sialic acid significantly correlated with systolic blood
      pressure, fasting serum cholesterol and triacylglycerol concentrations and body
      mass index in the females. In males serum total sialic acid significantly
      positively correlated with fasting serum cholesterol and triacylglycerol
      concentrations, and correlated inversely with the hip/waist ratio. 4. In multiple
      regression analysis of the 100 subjects serum total sialic acid correlated
      independently with fasting serum cholesterol, glucose and also plasma insulin
      concentrations. In females serum total sialic acid independently correlated with
      systolic and diastolic blood pressure, and serum cholesterol and fasting plasma
      glucose concentrations, although there was no significant independent correlation
      between serum total sialic acid and any of the other variables in the males.

PMID- 9662486
TI  - Gender differences in fat oxidation and sympathetic nervous system activity at
      rest and during submaximal exercise in older individuals.
AB  - 1. Gender differences in fat oxidation at rest and during exercise may contribute
      to higher body fat in women. We examined gender differences in fat oxidation at
      rest and during submaximal exercise and their relationship to sympathetic nervous
      system activity, free fatty acid availability, body composition and aerobic
      capacity in older volunteers. 2. We measured free fatty acid kinetics using
      [14C]palmitate, absolute (micromol/min) and relative (respiratory quotient) rates
      of fat oxidation by indirect calorimetry and sympathetic nervous system activity
      from noradrenaline kinetics using [3H]noradrenaline in 12 older men (70+/-4
      years) and 12 older women (66+/-4 years) at rest and during 30 min of submaximal
      exercise (45% of peak oxygen consumption). 3. At rest, men oxidized more fat than
      women on both an absolute (88+/-19 versus 51+/-15 micromol/min; P<0.01) and
      relative (respiratory quotient: 0.80+/-0. 04 versus 0.85+/-0.04; P<0.01) basis.
      These differences were not related to noradrenaline appearance rate, free fatty
      acid concentration, body composition or aerobic capacity. During exercise, fat
      oxidation was higher (P<0.05 to P<0.01) in men on an absolute level, but
      respiratory quotient did not differ. Higher absolute fat oxidation in men during
      exercise was explained by their higher absolute workload. Plasma free fatty acids
      and free fatty acid rate of appearance did not differ between men and women
      during exercise despite higher (P<0.05 to P<0.01) plasma noradrenaline
      concentrations in men. 4. We conclude that: (i) resting fat oxidation is higher
      in older men compared with older women independent of differences in
      noradrenaline appearance rate, free fatty acid availability, body composition or
      aerobic capacity, and (ii) despite higher plasma noradrenaline concentrations
      during submaximal exercise, no gender differences in free fatty acid appearance
      rate or fat oxidation were found. These results suggest a sex dimorphism in post
      absorptive fat metabolism in the elderly.

PMID- 9662487
TI  - Alterations in renal degradation of albumin in early experimental diabetes in the
      rat: a new factor in the mechanism of albuminuria.
AB  - 1. Albumin is normally excreted as a mixture of intact protein and fragments that
      are produced during renal passage. The purpose of this study was to investigate
      the ratio of intact versus degraded forms of excreted albumin to ascertain
      whether changes in this ratio could account for the apparent increase in albumin
      excretion seen in diabetes, as measured by standard radioimmunoassay techniques.
      2. Four-week male Sprague-Dawley rats with streptozotocin-induced diabetes and
      age-matched control rats were intravenously injected with [3H]albumin. Urine
      collected over 2 h was analysed by size exclusion chromatography and
      radioimmunoassay. A standard radioimmunoassay found a 7-fold increase in albumin
      excretion rate in diabetic rats, whereas there was only a 2-fold increase in
      albumin excretion (intact plus fragments). Urine analysed by size exclusion
      chromatography showed severe degradation for control rats (% monomer=4+/-2%); in
      diabetic rats there was a significant amount of monomer albumin excreted, along
      with moderately degraded and heavily degraded albumin (% monomer=17+/-5%). 3.
      This study has shown that the radioimmunoassay, which specifically detects intact
      albumin, considerably underestimates the amount of total urinary albumin which
      consists of intact and degraded material. The increase in albumin excretion rate
      observed in diabetes as measured by radioimmunoassay is mainly due to a change in
      the amount of intact albumin excreted and this is specifically due to the
      inhibition of albumin degradation at a post-glomerular site and not due to the
      onset of any type of glomerular 'shunt' pathway.

PMID- 9662488
TI  - Renal haemodynamics, sodium and water reabsorption during continuous intravenous
      infusion of recombinant interleukin-2.
AB  - 1. Renal haemodynamics, lithium and sodium clearance were measured in 14 patients
      treated with recombinant interleukin-2 for metastatic renal cell carcinoma. 2.
      Patients were studied before and after 72 h of continuous intravenous infusion of
      recombinant interleukin-2 (18x10(6) i.u..24 h-1.m-2) and 48 h post therapy.
      Cardiac output was measured by impedance cardiography. Effective renal plasma
      flow and glomerular filtration rate were determined by the renal clearances of
      131I-hippuran and 99mTc-diethylenetriaminepenta-acetic acid (DTPA) respectively.
      Renal clearance of lithium (CLi) was used as an index of proximal tubular
      outflow. 3. Treatment caused a transient decrease in mean arterial blood pressure
      and systemic vascular resistance, but cardiac output remained unchanged. Renal
      blood flow decreased and renal vascular resistance increased during and after
      treatment. Sodium clearance decreased from 1.10 (0.63/1.19) ml/min to 0.17
      (0.18/0.32) ml/min (P=0.003). Glomerular filtration rate remained unchanged,
      whereas the median CLi decreased from 26 (17/32) ml/min to 17 (10/21) ml/min
      (P=0.008). Calculated absolute proximal reabsorption rate of water increased from
      63 (40/69) ml/min to 71 (47/82) ml/min (P=0.04). The urinary excretion rate of
      thromboxane B2 and the ratio between excretion rates of thromboxane B2 and 6-keto
      prostaglandin-F1alpha increased by 98% (P=0.022) and 175% (P=0.022) respectively.
      4. The study suggests a specific recombinant interleukin-2-induced renal
      vasoconstrictor effect. Changes in renal prostaglandin synthesis may contribute
      to the decrease in renal blood flow. The lithium clearance data suggest that an
      increased proximal tubular reabsorption rate may contribute to the decreased
      sodium clearance during recombinant interleukin-2 treatment.

PMID- 9662489
TI  - Effect of propylthiouracil-induced hypothyroidism on the onset of skeletal muscle
      necrosis in dystrophin-deficient mdx mice.
AB  - 1. Duchenne and Becker muscular dystrophies are X-linked disorders caused by
      defects in muscle dystrophin. The mdx mouse is an animal model for Duchenne
      muscular dystrophy which has a point mutation in the dystrophin gene, resulting
      in little (<3%) or no expression of dystrophin in muscle. Mdx mice show a
      characteristic pattern of muscle necrosis and regeneration. Muscles are normal
      until the third postnatal week when widespread necrosis commences. This is
      followed by muscle regeneration, with the persistence of centrally nucleated
      fibres. 2. This work has examined the hypothesis that the onset of this muscle
      necrosis is associated with postnatal maturation of the thyroid endocrine system
      and that pharmacological inhibition of thyroid hormone synthesis delays the onset
      of muscle necrosis. 3. Serum T4 and T3 concentrations of mice were found to rise
      immediately before the onset of muscle necrosis in the mdx mouse, and induction
      of hypothyroidism by treatment of animals with propylthiouracil was found to
      delay the onset of muscle necrosis. 4. The results provide the first
      demonstration of experimental delay of muscle necrosis by manipulation of the
      endocrine system in muscle lacking dystrophin, and provide a novel insight into
      the way in which a lack of dystrophin interacts with postnatal development to
      precipitate muscle necrosis in the mdx mouse.

PMID- 9662490
TI  - Effects of morphine administration on the fetal production of oxytocin in labour.
AB  - 1. Animal and human work has indicated that maternal oxytocin secretion is under
      the control of endogenous opiates. Previous workers have described the fetal
      production of oxytocin in addition to maternal production. The study of the
      interaction between exogenously administered opiates and oxytocin secretion may
      give insight into the activity of any opiate-mediated regulatory mechanism of
      oxytocin secretion in the fetus. This study was designed to investigate the
      effect of an opiate (5 mg of morphine) given to the mother on the fetal
      production of oxytocin in labour. 2. Morphine was given by the attending
      clinicians for analgesic purposes to women in the first stage of labour. After
      delivery umbilical artery vein and maternal vein specimens were taken. 3. Four
      groups of patients were studied: women after normal vaginal delivery without
      analgesia in labour (n=10); women after normal vaginal delivery who had morphine
      administration in the first stage of labour (n=12); women who had an emergency
      Caesarean section in the first stage of labour (n=11); women who had an elective
      Caesarean section at term who were not in labour (n=11). 4. Oxytocin levels were
      measured by radioimmunoassay in the maternal vein, umbilical artery and umbilical
      vein specimens. Morphine was measured by radioimmunoassay in the umbilical vein
      specimens. 5. The umbilical artery minus vein concentration of oxytocin was
      calculated for each patient (A-V). There was no change in the umbilical (A-V)
      concentration of oxytocin if morphine had been given to the mother in labour;
      this applied to fetuses delivered vaginally or by Caesarean section. When the
      fetuses who were exposed to morphine were analysed separately, there was no
      correlation between the umbilical vein morphine concentration and the umbilical
      (A-V) oxytocin concentration either in Caesarean or vaginal deliveries. 6. Fetal
      oxytocin production was not affected by the maternal administration of morphine
      in the first stage of labour. This applies to the oxytocin production in the
      first and second stage of labour.

PMID- 9662491
TI  - A novel method for the visualization of the in situ mucus layer in rat and man.
AB  - 1. The observed thickness of the gastric mucus barrier varies widely, even
      appearing discontinuous, depending on the methods used. Here we describe the
      development and application of a modified periodic acid Schiff/Alcian Blue
      staining technique for use on cryostat sections of gastric mucosa. This technique
      for the first time enables the preservation and visualization of the full
      thickness of the adherent gastric mucus layer and the underlying mucosa. 2. In
      designing this novel method we have selected those procedures which would result
      in the least alteration to the mucus layer. The methods used were snap freezing,
      cryostat sectioning of the whole stomach followed by brief ethanol pretreatment
      (10 min in 100% ethanol), a prolonged staining with periodic acid Schiff/Alcian
      Blue (15 min and 2.5 h respectively), a gentle post-fixation (45 min
      paraformaldehyde vapour at 37 degreesC) and the use of a water-soluble mountant.
      3. A continuous, adherent mucus layer was observed over the surface of the rat
      gastric mucosa (periodic acid Schiff/Alcian Blue stained) and human gastric
      antral biopsies (periodic acid Schiff stained). In the rat the mean (S.D.) mucus
      thickness measurements along the antrum to oesophageal axis (which was divided
      histologically into four regions, A to D) were: A, 166 (47) micrometer; B, 179
      (48) micrometer; C, 184 (50) micrometer; D (the non-glandular stratified
      epithelium at the top of the stomach), Absent. In human gastric antral biopsies
      the mean (S.D.) mucus thickness was 144 (52) micrometer. 4. This new technique
      has enabled the visualization and precise measurement of thickness of the gastric
      mucus layer in rat and man. The adherent gastric mucus layer was observed to be
      continuous in the rat glandular stomach and human antrum. In validation
      experiments in rat the mean mucus thickness measurements were found to be twice
      those measured by conventional histological techniques, in which the mucus layer
      appeared discontinuous and patchy. However, they were within the range of
      thickness values seen in unfixed tissues and in the rat in vivo preparation.

PMID- 9662492
TI  - Intestinal permeability to polyethyleneglycol and sugars: a re-evaluation.
AB  - 1. Previous studies have indicated that the permeability of polyethyleneglycol
      across the human intestine is anomalously high in comparison with the
      permeability of sugars with similar molecular mass. In consequence it has been
      proposed that two or more distinct mechanisms must exist for the translocation of
      these classes of molecule or, alternatively, that the molecular parameter
      determining rate of penetration is each molecule's minimum molecular dimension.
      2. The notional hydrogen-bonding capacity of a molecule correlates well with oil
      water partition coefficient and also, in a variety of experimental systems, with
      rate of passive diffusion across biological membranes. A molecule's hydrogen
      bonding capacity is calculated by inspecting the structural formula and summing
      the individual theory-derived hydrogen-bonding capacities of the molecule's
      functional groups. 3. A classic set of intestinal permeability data that includes
      several ethyleneglycol oligomers and several sugars is re-analysed. A good
      correlation between permeability and hydrogen-bonding capacity is demonstrated.
      Specifically, there is no discontinuity between the polyethyleneglycols and the
      sugars. The data are compatible with a simple model in which all the molecules
      studied cross the intestine by passive diffusion across cellular membranes.

PMID- 9662493
TI  - The effect of the neuropeptide FMRFamide on Aplysia californica siphon
      motoneurons involves multiple ionic currents that vary seasonally.
AB  - The molluscan neuropeptide FMRFamide has a number of inhibitory actions on the
      sensory neurons and motoneurons mediating the defensive gill and siphon
      withdrawal reflex pathway of Aplysia californica. Exogenous application of
      FMRFamide has a biphasic, dual-polarity effect on the majority of LFS siphon
      motoneurons, causing a transient depolarization followed by a prolonged
      hyperpolarization. FMRFamide induces this response in LFS neurons by causing an
      increase in multiple ionic currents, including a transient Na+ current, a slow
      prolonged Na+ current, a 4-aminopyridine (4-AP)-sensitive K+ current and a 4-AP
      insensitive K+ current. We have found that a subset of LFS neurons exhibits an
      exclusively excitatory, biphasic response to FMRFamide, consisting of a transient
      depolarization followed by a prolonged depolarization of reduced magnitude. Over
      a period of 29 months, we consistently observed an increase in the incidence of
      the exclusively excitatory response during the summer months (June to September).
      From October to May, we observed an exclusively excitatory response to FMRFamide
      in 19 % of LFS neurons; yet, in the summer months, 51 % of LFS neurons exhibited
      this response pattern. We compared the ionic basis of the exclusively excitatory
      response to FMRFamide with the ionic mechanisms mediating the more frequently
      observed excitatory/inhibitory response. The exclusively excitatory response
      involves three of the same ionic components as the more typical
      excitatory/inhibitory response, including the activation of a transient Na+
      current, a slow prolonged Na+ current and a 4-AP-insensitive K+ current. The
      principal difference between the two response types is that FMRFamide fails to
      activate a 4-AP-sensitive K+ current in those LFS neurons that exhibit an
      exclusively excitatory response to the peptide. In addition, LFS neurons with an
      exclusively excitatory response tend to show a coordinated increase in the
      magnitude of the inward current component of the FMRFamide response. Together,
      these changes during the summer months may enable this modulatory peptide to
      bring LFS neurons to suprathreshold levels of activity for eliciting a siphon
      withdrawal and should substantially alter the neuromodulatory effects of the
      peptide.

PMID- 9662494
TI  - Relationships between blood pressure and heart rate in the saltwater crocodile
      Crocodylus porosus.
AB  - The cardiac limb of the baroreflex loop was studied in the saltwater crocodile
      Crocodylus porosus. The classical pharmacological methodology using phenylephrine
      and sodium nitroprusside was used to trigger blood pressure changes, and the
      resulting alterations in heart rate were analysed quantitatively using a logistic
      function. Interindividual differences in resting heart rates and blood pressures
      were observed, but all seven animals displayed clear baroreflex responses.
      Atropine and sotalol greatly attenuated the response. A maximal baroreflex gain
      of 7.2 beats min-1 kPa-1 was found at a mean aortic pressure of 6.1 kPa,
      indicating the active role of the baroreflex in a wide pressure range
      encompassing hypotensive and hypertensive states. At the lowest mean aortic
      pressures (5.0 kPa), the synergistic role of the pulmonary-to-systemic shunt in
      buffering the blood pressure drop also contributes to blood pressure regulation.
      Pulse pressure showed a better correlation with heart rate and also a higher gain
      than mean aortic, systolic or diastolic pressures, and this is taken as an
      indicator of the existence of a differential control element working
      simultaneously with a linear proportional element.

PMID- 9662495
TI  - Enhancement of insect antifreeze protein activity by solutes of low molecular
      mass.
AB  - Antifreeze proteins (AFPs) lower the non-equilibrium freezing point of water (in
      the presence of ice) below the melting point, thereby producing a difference
      between the freezing and melting points that has been termed thermal hysteresis.
      In general, the magnitude of the thermal hysteresis depends upon the specific
      activity and concentration of the AFP. This study describes several low-molecular
      mass solutes that enhance the thermal hysteresis activity of an AFP from
      overwintering larvae of the beetle Dendroides canadensis. The most active of
      these is citrate, which increases the thermal hysteresis nearly sixfold from 1.2
      degrees C in its absence to 6.8 degrees C. Solutes which increase activity
      approximately fourfold are succinate, malate, aspartate, glutamate and ammonium
      sulfate. Glycerol, sorbitol, alanine and ammonium bicarbonate increased thermal
      hysteresis approximately threefold. Interestingly, 0.5 mol l-1 sodium sulfate
      eliminated activity. Solute concentrations between 0.25 and 1 mol l-1 were
      generally required to elicit optimal thermal hysteresis activity. Glycerol is the
      only one of these enhancing solutes that is known to be present at these
      concentrations in overwintering D. canadensis, and therefore the physiological
      significance of most of these enhancers is unknown. The mechanism(s) of this
      enhancement is also unknown. The AFP used in this study (DAFP-4) is nearly
      identical to previously described D. canadensis AFPs. The mature protein consists
      of 71 amino acid residues arranged in six 12- or 13-mer repeats with a consensus
      sequence consisting of Cys-Thr-X3-Ser-X5-X6-Cys-X8-X9-Ala-X11-Thr-X1 3, where X3
      and X11 tend to be charged residues, X5 tends to be Thr or Ser, X6 to be Asn or
      Asp, X9 to be Asn or Lys and X13 to be Ala in the 13-mers. DAFP-4 is shorter by
      one repeat than previously described D. canadensis AFPs.

PMID- 9662496
TI  - Retinal location is the key to identifying predators in fiddler crabs (Uca
      pugilator).
AB  - Fiddler crabs (Uca pugilator Bosc; Crustacea, Decapoda) feed and court in open,
      flat spaces. Their visual system has several putative adaptations to their flat
      habitat, including the tendency to keep the vertical axis of their eyes
      perpendicular to the plane of the substratum. It is hypothesized that one of the
      functions of this behavior is to distinguish accurately predators from
      conspecifics by aligning the region of the eye sensitive to predators with the
      region in space in which predators occur. To test this hypothesis, a crab was
      placed in a glass dish, and a moving stimulus was presented between 20 degrees
      above and below eye level (horizontal). Stimuli below the crab's horizon hardly
      ever evoked escape responses, while identical stimuli above the horizon produced
      escape responses whose frequency varied with the angular size, not the absolute
      size, of the stimulus. Experiments with artificial horizons showed that it is the
      position of the stimulus relative to the eye that is important, rather than its
      position relative to external cues such as the visible horizon, the vertical
      light gradient or the gravitational horizon. It is concluded that a crab responds
      to stimuli according to their position relative to its retinal equator. This
      conclusion is discussed in light of the crabs' natural behavior with respect to
      supra-horizontal stimuli.

PMID- 9662497
TI  - Effects of wheat germ agglutinin and colchicine on microtubules of the
      mitochondria-rich cells and Ca2+ uptake in tilapia (Oreochromis mossambicus)
      larvae.
AB  - The organization of the microtubules and actin filaments in the gills of tilapia
      (Oreochromis mossambicus) larvae was revealed by confocal microscopy. The
      fluorescence intensity of the microtubules in the gills was increased by adding
      wheat germ agglutinin (WGA, 40 ng ml-1) to the ambient water for 30 min, but the
      staining pattern of the actin filaments was not changed. The fluorescence
      intensity of the microtubules in the gills was decreased by treatment with the
      microtubule-disrupting reagent colchicine at 0.2 mmol l-1 for 4 h. WGA treatment
      concurrently raised Ca2+ influx rates, and the increase was particularly large
      when the larvae were kept in water with extremely low Ca2+ levels ([Ca2+]=0.002
      mmol l-1). Colchicine treatment, in contrast, reduced the Ca2+ influx rate. These
      results indicate that the microtubule network in tilapia gills, particularly in
      mitochondria-rich cells, could play a critical role in the uptake of Ca2+ in
      tilapia larvae.

PMID- 9662498
TI  - Why do mayflies lay their eggs en masse on dry asphalt roads? Water-imitating
      polarized light reflected from asphalt attracts Ephemeroptera.
AB  - We report on dry asphalt roads acting as 'mayfly traps'; that is, they lure
      swarming, mating and egg-laying mayflies in large numbers. To explain this
      surprising behaviour, we performed multiple-choice experiments with Ephemeroptera
      in the field, and measured and compared the reflection-polarization
      characteristics of an asphalt road and a mountain creek from which mayflies
      emerge. We show here that Ephemeroptera can be deceived by and attracted to dry
      asphalt roads because of the strongly horizontally polarized light reflected from
      the surface. Asphalt surfaces can mimic a highly polarized water surface to
      Ephemeroptera. The darker and smoother the asphalt surface, the higher is the
      degree of polarization of reflected light and the more attractive is the road to
      mayflies. We show that mayflies detect water by means of polarotaxis; that is, on
      the basis of the partially and horizontally polarized reflected light. Asphalt
      roads are excellent markers for swarming Ephemeroptera because of their
      conspicuous elongated form; the sky above them is usually open, which is the
      prerequisite of mayfly mating, and the higher temperature of the asphalt prolongs
      the reproductive activity of mayflies. These additional factors enhance the
      attractiveness of asphalt roads to swarming mayflies. Thus, asphalt roads near
      ephemeropteran emergence sites (lakes, rivers and creeks) are a great danger for
      mayflies, because eggs laid on the asphalt inevitably perish. Asphalt roads can
      deceive and attract mayflies en masse like the ancient tar pits and asphalt seeps
      or the recent crude or waste oil lakes deceive, lure and trap polarization
      sensitive water-seeking insects in large numbers.

PMID- 9662499
TI  - Stress/strain behaviour of the equine laminar junction.
AB  - The equine laminar junction plays a vital role in transferring the forces of
      weight-bearing between the epidermal hoof wall and the bone of the third phalanx,
      but the way in which it performs this function is poorly understood. Using
      samples from sites varying proximodistally and circumferentially around the hoof,
      the stress/strain behaviour of this tissue was characterised in three directions:
      radial tension and proximodistal and mediolateral shear. The influences of toe
      angle and length were also examined. For all three test directions, the modulus
      of elasticity increased with increasing strain magnitude. The mean modulus of
      elasticity in tension was 18.25+/-5.38 MPa (mean +/-1 S.D., N=116; mean strain 0.
      25). In proximodistal shear, the mean shear modulus was 5.38+/-1.49 MPa (N=76;
      mean shear strain 0.48) and in mediolateral shear 2. 57+/-0.91 MPa (N=66; mean
      shear strain 0.81). In many cases, the individual hoof or horse from which the
      samples were taken significantly affected the value of the modulus, suggesting
      that mechanical history may affect the material properties of this tissue. Few
      biologically significant variations with location, toe length or toe angle were
      unambiguously demonstrated, suggesting that the material properties of the
      laminar junction are independent of position, despite apparent regional
      variations in function, and that foot shape is not a major determinant of
      material properties.

PMID- 9662500
TI  - The rhodopsin gene of the cuttlefish Sepia officinalis: sequence and spectral
      tuning.
AB  - The cephalopod molluscs are a group of invertebrates that occupy a wide range of
      oceanic photic environments. They are an ideal group of animals, therefore, in
      which to study the evolution of rhodopsin. The cDNA sequence of the rhodopsin
      gene of the cuttlefish Sepia officinalis (L.) (Sub-class Coleoidea, Order
      Sepiida) is presented, together with an analysis of the structure of the gene. A
      proline-rich C terminus is present; this structure is characteristic of
      cephalopod rhodopsins. In common with all invertebrate opsins studied so far, the
      equivalent site to the counterion in vertebrate opsins is occupied by an aromatic
      amino acid. An intron is present that splits codon 107, in contrast to the
      intronless rhodopsin gene in two species of myopsid squid. A spectral tuning
      model involving substitutions at only three amino acid sites is proposed for the
      spectral shifts between the rhodopsins of Sepia officinalis, three species of
      squid and Paroctopus defleini.

PMID- 9662501
TI  - Passive body movement and gas exchange in the frilled lizard (Chlamydosaurus
      kingii) and goanna (Varanus gouldii).
AB  - The saccular lung in lizards is large and highly compliant compared with
      mammalian lungs, and these properties led us to question to what extent body
      movements could affect pulmonary gas exchange and the partial pressure of
      arterial blood gases. Specimens of two species of lizards, the frilled lizard
      (Chlamydosaurus kingii, approximately 600 g body mass) and the goanna (Varanus
      gouldii, approximately 1400 mass), were anaesthetised, maintained at
      approximately 36 degreesC and mechanically hyperventilated to lower the arterial
      partial pressure of carbon dioxide (PaCO2) to below apnoeic threshold.
      Respiratory system compliance (Crs) averaged 0. 112 ml kg-1 Pa-1 (goanna) and
      0.173 ml kg-1 Pa-1 (frilled lizard), which is approximately 7-11 times the
      predicted value for a mammal of similar body mass. Mechanical ventilation was
      interrupted, and the changes in PaCO2 and PaO2 were monitored over the following
      10 min as the animal was either left immobile or subjected to imposed lateral
      body movements. During the post-hyperventilation apnoea, PaCO2 increased whereas
      PaO2 did not always fall, sometimes even increasing, suggesting a reduction in
      the importance of pulmonary shunts. No significant differences were detected in
      the time course of changes in arterial blood gas levels or heart rate between
      runs with or without body movement. We conclude that in these species of lizards,
      despite the high Crs, lateral chest wall movements neither hinder nor favour
      pulmonary gas exchange.

PMID- 9662502
TI  - Changes in the reproductive system of the snail Helix aspersa caused by mucus
      from the love dart.
AB  - The function of the love dart in certain species of terrestrial snails is
      unknown. In Helix aspersa, the dart is a sharp calcareous structure that is used
      to pierce the partner's skin during courtship. When expelled, the dart is covered
      with a thick mucus. The hypothesis tested here is that the mucus contains a
      biologically active substance. Extracts of the digitiform glands that produce
      this mucus were applied to parts of the reproductive system in vitro. The
      extracts triggered an initial reconfiguration of the copulatory canal that caused
      the bursa tract diverticulum to become more accessible to the spermatophore. The
      reconfiguration of the copulatory canal also closed off the tract leading to the
      bursa copulatrix, a sperm-digesting organ. A few minutes after the initial
      contraction, the peristaltic contractions in the diverticulum became
      significantly more frequent. This latter effect continued for at least 1 h,
      provided that the mucus extract remained in the saline bath. The minimum
      effective dosage was less than the 2.2 mg of mucus transferred with the dart.
      Sperm competition is expected in Helix aspersa since multiple matings occur
      before eggs are laid. By influencing the female organs involved in the processing
      of foreign sperm, the dart shooter may increase the chance that his sperm will
      fertilise eggs.

PMID- 9662503
TI  - Mechanisms of thermal balance in flying Centris pallida (Hymenoptera:
      Anthophoridae).
AB  - Thermoregulation of the thorax is critical for bees and other endothermic insects
      to achieve high rates of flight muscle power production. However, the mechanisms
      allowing insects to regulate thorax temperatures during flight are not well
      understood. To test whether variations in metabolic heat production, evaporation
      or heat transfer from the thorax to the abdomen contribute to the maintenance of
      stable body temperatures during flight in the bee Centris pallida, we measured
      CO2 production, water vapor loss, wingbeat frequency and body segment
      temperatures during flight at varying air temperatures (Ta). While hovering in
      the field and while flying in the respirometer, C. pallida males maintain
      extremely stable, elevated thorax temperatures (45+/-2 degrees C; mean +/-
      S.E.M.). Measurements of head, thorax and abdomen temperatures as a function of
      Ta during hovering flight in the field indicated that C. pallida males were not
      actively increasing heat transfer from the thorax to the head or abdomen at high
      Ta values. As Ta increased from 26 to 35 degrees C, increases in evaporative
      water loss were relatively small compared with the decrease in carbon dioxide
      emission. As Ta values increased from 26 to 35 degrees C, the factorial decreases
      in metabolic heat production and the elevation of thorax temperature above Ta
      were closely matched (35 %), suggesting that variation in metabolic heat
      production is the major mechanism of thermoregulation in flying C. pallida. The
      thermal effects on rates of water loss and metabolic water production resulted in
      a strong positive water balance at cooler Ta values, but a strong negative water
      balance at Ta values above 31 degrees C. During the first minute of flight in the
      respirometry chamber, wingbeat frequency was independent of Ta. However, by the
      fourth minute, there was a significant negative relationship between Ta and
      wingbeat frequency, which was similar to the thermal relationship observed for
      wingbeat frequency in the field. These data suggest that, either through
      homeostatic regulation or resulting secondarily from thermal effects on flight
      motor properties, variation in metabolic heat production may occur via altered
      wingbeat kinematics.

PMID- 9662504
TI  - Utilisation of substrates during tethered flight with and without lift generation
      in the African fruit beetle Pachnoda sinuata (Cetoniinae).
AB  - We have investigated the pattern of metabolic changes during tethered flight with
      and without lift generation in the African fruit beetle Pachnoda sinuata. Two
      distinct metabolic phases occur during lift-generating flight. The first phase is
      characterised by a high rate of oxygen consumption and a rapid change in proline
      and alanine levels in the haemolymph and flight muscles and in glycogen level in
      the flight muscles. Carbohydrates are released from the fat body into the
      haemolymph. These carbohydrates are oxidised during the second phase. Changes in
      proline and alanine levels in the haemolymph and flight muscles and in glycogen
      level in the flight muscles are minor during the second phase and the rate of
      oxygen consumption is reduced. During lift-generating flight, metabolic changes
      are rapid. Proline concentrations in the haemolymph and flight muscles fall
      dramatically during the first 30 s of flight, while alanine concentrations rise
      concomitantly. While haemolymph concentrations of proline and alanine remain
      virtually unchanged thereafter, further changes in the levels of these amino
      acids occur in the flight muscles during 5 min of flight. The initial levels of
      the two amino acids in the flight muscles are re-established over 1 h of rest
      following a 5 min flight, while this process takes longer in the haemolymph. The
      concentration of haemolymph carbohydrates increases during the first 30 s of
      flight and declines thereafter during 5 min of flight. The pre-flight levels are
      restored after 1 h of subsequent rest. The stores of glycogen in the flight
      muscles are rapidly diminished during the first 10 s of flight and decrease at a
      lower rate during further flight lasting up to 5 min. A subsequent 1 h of rest is
      sufficient almost to restore pre-flight levels. Haemolymph lipid levels are
      slightly but significantly increased during 11 min of flight and after 1 h of
      subsequent rest. During flight without lift production, the metabolic changes are
      considerably slower and beetles fly approximately seven times longer than during
      lift-generating flight. Resting basalar (BM), dorso-ventral (DVM) and dorso
      longitudinal (DLM) flight muscles show no differences in levels of proline,
      alanine and glycogen. After different periods of flight, during which lift and
      wing loading were minimised, the DVM was found to have the highest level of
      proline after 5 min of flight. Levels of alanine in the DVM were lower than in
      the DLM. There was no evidence to suggest that different flight muscles are
      specialised for either proline or carbohydrate utilisation. Proline and
      carbohydrates participate equally in supplying energy to the flight muscles
      during lift-generating flight. The contribution to the energy supply by the
      flight muscles is 54 %, while that of the haemolymph is 46 %.

PMID- 9662505
TI  - Synthesis and biological properties of C12,13-cyclopropyl-epothilone A and
      related epothilones.
AB  - BACKGROUND: The epothilones are natural substances that are potently cytotoxic,
      having an almost identical mode of action to Taxoltrade mark as tubulin
      polymerization and microtubule-stabilizing agents. The development of detailed
      structure-activity relationships for these compounds and the further elucidation
      of their mechanism of action is of high priority. RESULTS: The chemical synthesis
      of the C12,13-cyclopropyl analog of epothilone A and its C12,13-trans
      diastereoisomer has been accomplished. These compounds and several other
      epothilone analogs have been screened for their ability to induce tubulin
      polymerization and death of a number of tumor cells. Several interesting
      structure-activity trends within this family of compounds were identified.
      CONCLUSIONS: The results of the biological tests conducted in this study have
      demonstrated that, although a number of positions on the epothilone skeleton are
      amenable to modification without significant loss of biological activity, the
      replacement of the epoxide moiety of epothilone A with a cyclopropyl group leads
      to total loss of activity.

PMID- 9662506
TI  - Specificity of aminoglycoside antibiotics for the A-site of the decoding region
      of ribosomal RNA.
AB  - BACKGROUND: Aminoglycoside antibiotics bind to the A-site of the decoding region
      of 16S RNA in the bacterial ribosome, an interaction that is probably responsible
      for their activity. A detailed study of the specificity of aminoglycoside binding
      to A-site RNA would improve our understanding of their mechanism of antibiotic
      activity. RESULTS: We have studied the binding specificity of several
      aminoglycosides with model RNA sequences derived from the 16S ribosomal A-site
      using surface plasmon resonance. The 4,5-linked (neomycin) class of
      aminoglycosides showed specificity for wild-type A-site sequences, but the 4,6
      linked class (kanamycins and gentamicins), generally showed poor specificity for
      the same sequences. Methylation of a cytidine in the target RNA, as found in the
      Escherichia coli ribosome, had negligible effects on aminoglycoside binding.
      CONCLUSIONS: Although both 4,5- and 4, 6-linked aminoglycosides target the same
      ribosomal site, they appear to bind and effect antibiotic activity in different
      manners. The aminoglycosides might recognize different RNA conformations or the
      interaction might involve different RNA tertiary structures that are not equally
      sampled in our ribosome-free model. These results imply that models of ribosomal
      RNA must be carefully designed if the data are expected to accurately reflect
      biological activity.

PMID- 9662507
TI  - Kinetics and regioselectivity of peptide-to-heterocycle conversions by microcin
      B17 synthetase.
AB  - BACKGROUND: The Escherichia coli peptide antibiotic microcin B17 (MccB17)
      contains four oxazole and four thiazole rings introduced post-translationally in
      the 69 amino acid McbA gene product, an MccB17 precursor, by the microcin B,C,D
      enzyme complex. Both monocyclic and 4,2-bis-heterocyclic moieties are generated.
      The enzymatic cyclization involves 14 of the last 43 amino acids of McbA and
      requires the presence of the first 26 amino acids that function as a specificity
      conferring propeptide. RESULTS: We have constructed maltose-binding protein (MBP)
      McbA1-46 fusion proteins and have mutagenized the Gly39-Ser40-Cys41 (GSC) wild
      type sequence to assess the regioselectivity and chemoselectivity of MccB17
      synthetase-mediated heterocycle formation at the first two loci, residues 40 and
      41 of McbA. Four single-site and four double-site substrates showed substantial
      differences in turnover as assessed by western assays, UV-visible spectroscopy
      and mass spectrometry. Cysteine-derived thiazoles form at a greater rate than
      serine-derived oxazoles. Formation of bis-heterocycles is sensitive both to
      composition and sequence context. CONCLUSIONS: The E. coli McbB,C,D MccB17
      synthetase is the first peptide heterocyclization enzyme to be characterized.
      This study reveals substantial regioselectivity and chemoselectivity (thiazole >
      oxazole) at the most amino-terminal bis-heterocyclization site of McbA. The
      heterocyclization of GSS and GCC mutants of McbA1-46 by MccB17 synthetase
      demonstrates that the complex can efficiently generate tandem bis-oxazoles and
      bis-thiazoles, moieties not found in MccB17 but present in natural products such
      as hennoxazole and bleomycin. The observations suggest a common enzymatic
      mechanism for the formation of peptide-derived heterocyclic natural products.

PMID- 9662508
TI  - TGF-beta-signaling with small molecule FKBP12 antagonists that bind myristoylated
      FKBP12-TGF-beta type I receptor fusion proteins.
AB  - BACKGROUND: Growth arrest in many cell types is triggered by transforming growth
      factor beta (TGF-beta), which signals through two TGF-beta receptors (type I, TGF
      beta RI, and type II, TGF-beta). In the signaling pathway, TGF-beta binds to the
      extracellular domain of TGF-betaRII, which can then transphosphorylate TGF-betaRI
      in its glycine/serine (GS)-rich box. Activated TGF-betaRI phosphorylates two
      downstream effectors, Smad2 and Smad3, leading to their translocation into the
      nucleus. Cell growth is arrested and plasminogen activator inhibitor 1 (PAI-1) is
      upregulated. We investigated the role of the immunophilin FKBP12, which can bind
      to the GS box of TGF-betaRI, in TGF-beta signaling. RESULTS: Overexpression of
      myristoylated TGF-betaRI and TGF-betaRII cytoplasmic tails caused constitutive
      nuclear translocation of a green-fluorescent-protein-Smad2 construct in COS-1
      cells, and constitutive activation of a PAI-1 reporter plasmid in mink lung
      cells. Fusing FKBP12 to TGF-betaRI resulted in repression of autosignaling that
      could be alleviated by FK506M or rapamycin (two small molecules that can bind to
      FKBP12). Mutation of the FKBP12-binding site in the FKBP1-TGF-betaRI fusion
      protein restored constitutive signaling. An acidic mutation in the FKBP12-TGF
      betaRI protein allowed FKBP12 antagonists to activate signaling in the absence of
      TGF-betaRII. Further mutations in the TGF-betaRI FKBP12-binding site resulted in
      TGF-beta signaling that was independent of both TGF-betaRII and FKBP12
      antagonists. CONCLUSIONS: Fusing FKBP12 to TGF-betaRI results in a novel receptor
      that is activated by small molecule FKBP12 antagonists. These results suggest
      that FKBP12 binding to TGF-betaRI is inhibitory and that FKBP12 plays a role in
      inhibiting TGF-beta superfamily signals.

PMID- 9662509
TI  - Engineering protein kinases with distinct nucleotide specificities and inhibitor
      sensitivities by mutation of a single amino acid.
AB  - A major goal of signal transduction research is to identify the substrates and
      roles of the many protein kinases. The task might be simplified by the discovery
      that the mutation of a single amino acid dramatically alters the nucleotide
      specificity of protein kinases and their inhibition by a particular class of anti
      inflammatory drug.

PMID- 9662510
TI  - The high-potential flavin and heme of nitric oxide synthase are not magnetically
      linked: implications for electron transfer.
AB  - BACKGROUND: The homodimeric nitric oxide synthase (NOS) catalyzes conversion of L
      arginine to L-citrulline and nitric oxide. Each subunit contains two flavins and
      one protoporphyrin IX heme. A key component of the reaction is the transfer of
      electrons from the flavins to the heme. The NOS gene encodes two domains linked
      by a short helix containing a calmodulin-recognition sequence. The reductase
      domain binds the flavin cofactors, while the oxygenase domain binds heme and L
      arginine and additionally mediates the dimerization of the NOS subunits. We
      investigated the origin of the unusual magnetic properties (rapid-spin
      relaxation) of an air-stable free radical localized to a reductase domain flavin
      cofactor. RESULTS: We characterized the air-stable flavin in wild-type NOS, both
      in the presence and absence of calcium and calmodulin, the imidazole-bound heme
      complex of wild-type NOS, the NOS Cys415-->Ala mutant, and the isolated reductase
      domain. All preparations of NOS had the same flavin electron-spin relaxation
      behavior. No half-field transitions or temperature-dependent changes in the
      linewidth of the radical spin signal were detected. CONCLUSIONS: These data
      suggest that the observed relaxation enhancement of the NOS flavin radical is
      caused by the environment provided by the reductase domain. No magnetic
      interaction between the heme and flavin cofactors was detected, suggesting that
      the flavin and heme centers are probably separated by more than 15 A.

PMID- 9662511
TI  - Engineering proteins: keeping up with biology.
AB  - A wide range of biological laboratories have adopted protein engineering
      techniques, altering the way biochemical research is carried out. Ironically,
      this broad success has increased the challenges faced by researchers at the
      chemistry-biology interface.

PMID- 9662512
TI  - Elsewhere in biology 

PMID- 9662513
TI  - Total recall helicon therapeutics, Inc 

PMID- 9662514
TI  - Creating web pages 

PMID- 9662515
TI  - The two-component system. Regulation of diverse signaling pathways in prokaryotes
      and eukaryotes.

PMID- 9662516
TI  - Evolution of C4 photosynthesis in flaveria species. Isoforms Of nadp-malic enzyme
AB  - NADP-malic enzyme (NADP-ME, EC 1.1.1.40), a key enzyme in C4 photosynthesis,
      provides CO2 to the bundle-sheath chloroplasts, where it is fixed by ribulose-1,5
      bisphosphate carboxylase/oxygenase. We characterized the isoform pattern of NADP
      ME in different photosynthetic species of Flaveria (C3, C3-C4 intermediate, C4
      like, C4) based on sucrose density gradient centrifugation and isoelectric
      focusing of the native protein, western-blot analysis of the denatured protein,
      and in situ immunolocalization with antibody against the 62-kD C4 isoform of
      maize. A 72-kD isoform, present to varying degrees in all species examined, is
      predominant in leaves of C3 Flaveria spp. and is also present in stem and root
      tissue. By immunolabeling, NADP-ME was found to be mostly localized in the upper
      palisade mesophyll chloroplasts of C3 photosynthetic tissue. Two other isoforms
      of the enzyme, with molecular masses of 62 and 64 kD, occur in leaves of certain
      intermediates having C4 cycle activity. The 62-kD isoform, which is the
      predominant highly active form in the C4 species, is localized in bundle-sheath
      chloroplasts. Among Flaveria spp. there is a 72-kD constitutive form, a 64-kD
      form that may have appeared during evolution of C4 metabolism, and a 62-kD form
      that is necessary for the complete functioning of C4 photosynthesis.

PMID- 9662517
TI  - High aluminum resistance in buckwheat. I. Al-induced specific secretion of oxalic
      acid from root tips 
AB  - High Al resistance in buckwheat (Fagopyrum esculentum Moench. cv Jianxi) has been
      suggested to be associated with both internal and external detoxification
      mechanisms. In this study the characteristics of the external detoxification
      mechanism, Al-induced secretion of oxalic acid, were investigated. Eleven days of
      P depletion failed to induce secretion of oxalic acid. Exposure to 50 &mgr;M
      LaCl3 also did not induce the secretion of oxalic acid, suggesting that this
      secretion is a specific response to Al stress. Secretion of oxalic acid was
      maintained for 8 h by a 3-h pulse treatment with 150 &mgr;M Al. A nondestructive
      method was developed to determine the site of the secretion along the root.
      Oxalic acid was found to be secreted in the region 0 to 10 mm from the root tip.
      Experiments using excised roots also showed that secretion was located on the
      root tip. Four kinds of anion-channel inhibitors showed different effects on Al
      induced secretion of oxalic acid: 10 &mgr;M anthracene-9-carboxylic acid and 4,
      4'-diisothiocyanatostilbene-2,2'-disulfonate had no effect, niflumic acid
      stimulated the secretion 4-fold, and phenylglyoxal inhibited the secretion by
      50%. Root elongation in buckwheat was not inhibited by 25 &mgr;M Al or 10 &mgr;M
      phenylglyoxal alone but was inhibited by 40% in the presence of Al and
      phenylglyoxal, confirming that secretion of oxalic acid is associated with Al
      resistance.

PMID- 9662518
TI  - High aluminum resistance in buckwheat. Ii. Oxalic acid detoxifies aluminum
      internally 
AB  - Buckwheat (Fagopyrum esculentum Moench. cv Jianxi), which shows high Al
      resistance, accumulates Al in the leaves. The internal detoxification mechanism
      was studied by purifying and identifying Al complexes in the leaves and roots.
      About 90% of Al accumulated in the leaves was found in the cell sap, in which the
      dominant organic acid was oxalic acid. Purification of the Al complex in the cell
      sap of leaves by molecular-sieve chromatography resulted in a complex with a
      ratio of Al to oxalic acid of 1:3. A 13C-nuclear magnetic resonance study of the
      purified cell sap revealed only one signal at a chemical shift 164.4 ppm, which
      was assigned to the Al-chelated carboxylic group of oxalic acid. A 27Al-nuclear
      magnetic resonance analysis revealed one major signal at the chemical shift of
      16.0 to 17.0 ppm, with a minor signal at the chemical shift of 11.0 to 12 ppm in
      both the intact roots and their cell sap, which is consistent with the Al-oxalate
      complexes at 1:3 and 1:2 ratios, respectively. The purified cell sap was not
      phytotoxic to root elongation in corn (Zea mays). All of these results indicate
      that Al tolerance in the roots and leaves of buckwheat is achieved by the
      formation of a nonphytotoxic Al-oxalate (1:3) complex.

PMID- 9662519
TI  - Developmental expression and substrate specificities of alfalfa caffeic acid 3-O
      methyltransferase and caffeoyl coenzyme A 3-O-methyltransferase in relation to
      lignification.
AB  - The biosynthesis of monolignols can potentially occur via two parallel pathways
      involving free acids or their coenzyme A (CoA) esters. Caffeic acid 3-O
      methyltransferase (COMT) and caffeoyl CoA 3-O-methyltransferase (CCOMT) catalyze
      functionally identical reactions in these two pathways, resulting in the
      formation of mono- or dimethoxylated lignin precursors. The activities of the two
      enzymes increase from the first to the sixth internode in stems of alfalfa
      (Medicago sativa L.), preceding the deposition of lignin. Alfalfa CCOMT is highly
      similar at the amino acid sequence level to the CCOMT from parsley, although it
      contains a six-amino acid insertion near the N terminus. Transcripts encoding
      both COMT and CCOMT are primarily localized to vascular tissue in alfalfa stems.
      Alfalfa CCOMT expressed in Escherichia coli catalyzes O-methylation of caffeoyl
      and 5-hydroxyferuloyl CoA, with preference for caffeoyl CoA. It has low activity
      against the free acids. COMT expressed in E. coli is active against both caffeic
      and 5-hydroxyferulic acids, with preference for the latter compound.
      Surprisingly, very little extractable O-methyltransferase activity versus 5
      hydroxyferuloyl CoA is present in alfalfa stem internodes, in which relative O
      methyltransferase activity against 5-hy-droxyferulic acid increases with
      increasing maturity, correlating with increased lignin methoxyl content.

PMID- 9662520
TI  - Overexpression of a homeobox gene, LeT6, reveals indeterminate features in the
      tomato compound leaf 
AB  - The cultivated tomato (Lycopersicon esculentum) has a unipinnate compound leaf.
      In the developing leaf primordium, major leaflet initiation is basipetal, and
      lobe formation and early vascular differentiation are acropetal. We show that
      engineered alterations in the expression of a tomato homeobox gene, LeT6, can
      cause dramatic changes in leaf morphology. The morphological states are variable
      and unstable and the phenotypes produced indicate that the tomato leaf has an
      inherent level of indeterminacy. This is manifested by the production of multiple
      orders of compounding in the leaf, by numerous shoot, inflorescence, and floral
      meristems on leaves, and by the conversion of rachis-petiolule junctions into
      "axillary" positions where floral buds can arise. Overexpression of a
      heterologous homeobox transgene, kn1, does not produce such phenotypic
      variability. This indicates that LeT6 may differ from the heterologous kn1 gene
      in the effects manifested on overexpression, and that 35S-LeT6 plants may be
      subject to alterations in expression of both the introduced and endogenous LeT6
      genes. The expression patterns of LeT6 argue in favor of a fundamental role for
      LeT6 in morphogenesis of leaves in tomato and also suggest that variability in
      homeobox gene expression may account for some of the diversity in leaf form seen
      in nature.

PMID- 9662521
TI  - Localization of expression of three cold-induced genes, blt101, blt4. 9, and
      blt14, in different tissues of the crown and developing leaves of cold-acclimated
      cultivated barley 
AB  - Tissues expressing mRNAs of three cold-induced genes, blt101, blt14, and blt4.9,
      and a control gene, elongation factor 1alpha, were identified in the crown and
      immature leaves of cultivated barley (Hordeum vulgare L. cv Igri). Hardiness and
      tissue damage were assessed. blt101 and blt4.9 mRNAs were not detected in control
      plants; blt14 was expressed in control plants but only in the inner layers of the
      crown cortex. blt101 was expressed in many tissues of cold-acclimated plants but
      most strongly in the vascular-transition zone of the crown; blt14 was expressed
      only in the inner layers of the cortex and in cell layers partly surrounding
      vascular bundles in the vascular-transition zone; expression of blt4.9, which
      codes for a nonspecific lipid-transfer protein, was confined to the epidermis of
      the leaf and to the epidermis of the older parts of the crown. None of the cold
      induced genes was expressed in the tunica, although the control gene was most
      strongly expressed there. Thus, the molecular aspects of acclimation differed
      markedly between tissues. Damage in the vascular-transition zone of the crown
      correlated closely with plant survival. Therefore, the strong expression of
      blt101 and blt14 in this zone may indicate a direct role in freezing tolerance of
      the crown.

PMID- 9662522
TI  - The expression of light-regulated genes in the high-pigment-1 mutant of tomato 
AB  - Three light-regulated genes, chlorophyll a/b-binding protein (CAB), ribulose-1,5
      bisphosphate carboxylase/oxygenase small subunit, and chalcone synthase (CHS),
      are demonstrated to be up-regulated in the high-pigment-1 (hp-1) mutant of tomato
      (Lycopersicon esculentum Mill. ) compared with wild type (WT). However, the
      pattern of up-regulation of the three genes depends on the light conditions,
      stage of development, and tissue studied. Compared with WT, the hp-1 mutant
      showed higher CAB gene expression in the dark after a single red-light pulse and
      in the pericarp of immature fruits. However, in vegetative tissues of light-grown
      seedlings and adult plants, CAB mRNA accumulation did not differ between WT and
      the hp-1 mutant. The ribulose-1,5-bisphosphate carboxylase/oxygenase small
      subunit mRNA accumulated to a higher level in the hp-1 mutant than WT under all
      light conditions and tissues studied, whereas CHS gene expression was up
      regulated in de-etiolated vegetative hp-1-mutant tissues only. The CAB and CHS
      genes were shown to be phytochrome regulated and both phytochrome A and B1 play a
      role in CAB gene expression. These observations support the hypothesis that the
      HP-1 protein plays a general repressive role in phytochrome signal transduction.

PMID- 9662523
TI  - Induction of defense-related responses in Cf9 tomato cells by the AVR9 elicitor
      peptide of cladosporium fulvum is developmentally regulated 
AB  - The AVR9 elicitor from the fungal pathogen Cladosporium fulvum induces defense
      related responses, including cell death, specifically in tomato (Lycopersicon
      esculentum Mill.) plants that carry the Cf-9 resistance gene. To study
      biochemical mechanisms of resistance in detail, suspension cultures of tomato
      cells that carry the Cf-9 resistance gene were initiated. Treatment of cells with
      various elicitors, except AVR9, induced an oxidative burst, ion fluxes, and
      expression of defense-related genes. Agrobacterium tumefaciens-mediated
      transformation of Cf9 tomato leaf discs with Avr9-containing constructs resulted
      efficiently in transgenic callus formation. Although transgenic callus tissue
      showed normal regeneration capacity, transgenic plants expressing both the Cf-9
      and the Avr9 genes were never obtained. Transgenic F1 seedlings that were
      generated from crosses between tomato plants expressing the Avr9 gene and wild
      type Cf9 plants died within a few weeks. However, callus cultures that were
      initiated on cotyledons from these seedlings could be maintained for at least 3
      months and developed similarly to callus cultures that contained only the Cf-9 or
      the Avr9 gene. It is concluded, therefore, that induction of defense responses in
      Cf9 tomato cells by the AVR9 elicitor is developmentally regulated and is absent
      in callus tissue and cell-suspension cultures, which consists of undifferentiated
      cells. These results are significant for the use of suspension-cultured cells to
      investigate signal transduction cascades.

PMID- 9662524
TI  - Analysis of promoter activity for the gene encoding pyruvate orthophosphate
      dikinase in stably transformed C4 flaveria species 
AB  - The C4 enzyme pyruvate orthophosphate dikinase is encoded by a single gene, Pdk,
      in the C4 plant Flaveria trinervia. This gene also encodes enzyme isoforms
      located in the chloroplast and in the cytosol that do not have a function in C4
      photosynthesis. Our goal is to identify cis-acting DNA sequences that regulate
      the expression of the gene that is active in the C4 cycle. We fused 1.5 kb of a
      5' flanking region from the Pdk gene, including the entire 5' untranslated
      region, to the uidA reporter gene and stably transformed the closely related C4
      species Flaveria bidentis. beta-Glucuronidase (GUS) activity was detected at high
      levels in leaf mesophyll cells. GUS activity was detected at lower levels in
      bundle-sheath cells and stems and at very low levels in roots. This lower-level
      GUS expression was similar to the distribution of mRNA encoding the
      nonphotosynthetic form of the enzyme. We conclude that cis-acting DNA sequences
      controlling the expression of the C4 form in mesophyll cells and the chloroplast
      form in other cells and organs are co-located within the same 5' region of the
      Pdk gene.

PMID- 9662525
TI  - Sorbitol-6-phosphate dehydrogenase expression in transgenic tobacco. High amounts
      of sorbitol lead to necrotic lesions 
AB  - We analyzed transgenic tobacco (Nicotiana tabacum L.) expressing Stpd1, a cDNA
      encoding sorbitol-6-phosphate dehydrogenase from apple, under the control of a
      cauliflower mosaic virus 35S promoter. In 125 independent transformants variable
      amounts of sorbitol ranging from 0.2 to 130 &mgr;mol g-1 fresh weight were found.
      Plants that accumulated up to 2 to 3 &mgr;mol g-1 fresh weight sorbitol were
      phenotypically normal, with successively slower growth as sorbitol amounts
      increased. Plants accumulating sorbitol at 3 to 5 &mgr;mol g-1 fresh weight
      occasionally showed regions in which chlorophyll was partially lost, but at
      higher sorbitol amounts young leaves of all plants lost chlorophyll in irregular
      spots that developed into necrotic lesions. When sorbitol exceeded 15 to 20
      &mgr;mol g-1 fresh weight, plants were infertile, and at even higher sorbitol
      concentrations the primary regenerants were incapable of forming roots in culture
      or soil. In mature plants sorbitol amounts varied with age, leaf position, and
      growth conditions. The appearance of lesions was correlated with high sorbitol,
      glucose, fructose, and starch, and low myo-inositol. Supplementing myo-inositol
      in seedlings and young plants prevented lesion formation. Hyperaccumulation of
      sorbitol, which interferes with inositol biosynthesis, seems to lead to osmotic
      imbalance, possibly acting as a signal affecting carbohydrate allocation and
      transport.

PMID- 9662526
TI  - The never ripe mutant provides evidence that tumor-induced ethylene controls the
      morphogenesis of agrobacterium tumefaciens-induced crown galls on tomato stems 
AB  - We confirm the hypothesis that Agrobacterium tumefaciens-induced galls produce
      ethylene that controls vessel differentiation in the host stem of tomato
      (Lycopersicon esculentum Mill.). Using an ethylene-insensitive mutant, Never ripe
      (Nr), and its isogenic wild-type parent we show that infection by A. tumefaciens
      results in high rates of ethylene evolution from the developing crown galls.
      Ethylene evolution from isolated internodes carrying galls was up to 50-fold
      greater than from isolated internodes of control plants when measured 21 and 28 d
      after infection. Tumor-induced ethylene substantially decreased vessel diameter
      in the host tissues beside the tumor in wild-type stems but had a very limited
      effect in the Nr stems. Ethylene promoted the typical unorganized callus shape of
      the gall, which maximized the tumor surface in wild-type stems, whereas the galls
      on the Nr stems had a smooth surface. The combination of decreased vessel
      diameter in the host and increased tumor surface ensured water-supply priority to
      the growing gall over the host shoot. These results indicate that in addition to
      the well-defined roles of auxin and cytokinin, there is a critical role for
      ethylene in determining crown-gall morphogenesis.

PMID- 9662527
TI  - Temperature-stress-induced impairment of chlorophyll biosynthetic reactions in
      cucumber and wheat 
AB  - Chlorophyll (Chl) biosynthesis in chill (7 degreesC)- and heat (42 degreesC)
      stressed cucumber (Cucumis sativus L. cv poinsette) seedlings was affected by 90
      and 60%, respectively. Inhibition of Chl biosynthesis was partly due to
      impairment of 5-aminolevulinic acid biosynthesis both in chill- (78%) and heat
      stress (70%) conditions. Protochlorophyllide (Pchlide) synthesis in chill- and
      heat-stressed seedlings was inhibited by 90 and 70%, respectively. Severe
      inhibition of Pchlide biosynthesis in chill-stressed seedlings was caused by
      inactivations of all of the enzymes involved in protoporphyrin IX (Proto IX)
      synthesis, Mg-chelatase, and Mg-protoporphyrin IX monoester cyclase. In heat
      stressed seedlings, although 5-aminolevulinic acid dehydratase and
      porphobilinogen deaminase were partially inhibited, one of the porphyrinogen
      oxidizing enzymes, uroporphyrinogen decarboxylase, was stimulated and
      coproporphyrinogen oxidase and protoporphyrinogen oxidase were not substantially
      affected, which demonstrated that protoporphyrin IX synthesis was relatively more
      resistant to heat stress. Pchlide oxidoreductase, which is responsible for
      phototransformation of Pchlide to chlorophyllide, increased in heat-stress
      conditions by 46% over that of the control seedlings, whereas it was not affected
      in chill-stressed seedlings. In wheat (Triticum aestivum L. cv HD2329) seedlings
      porphobilinogen deaminase, Pchlide synthesis, and Pchlide oxidoreductase were
      affected in a manner similar to that of cucumber, suggesting that temperature
      stress has a broadly similar effect on Chl biosynthetic enzymes in both cucumber
      and wheat.

PMID- 9662529
TI  - Phosphorylated alpha(1-->4)Glucans as substrate for potato starch-branching
      enzyme I 
AB  - The possible involvement of potato (Solanum tuberosum L.) starch-branching enzyme
      I (PSBE-I) in the in vivo synthesis of phosphorylated amylopectin was
      investigated in in vitro experiments with isolated PSBE-I using 33P-labeled
      phosphorylated and 3H end-labeled nonphosphorylated alpha(1-->4)glucans as the
      substrates. From these radiolabeled substrates PSBE-I was shown to catalyze the
      formation of dual-labeled (3H/33P) phosphorylated branched polysaccharides with
      an average degree of polymerization of 80 to 85. The relatively high molecular
      mass indicated that the product was the result of multiple chain-transfer
      reactions. The presence of alpha(1-->6) branch points was documented by
      isoamylase treatment and anion-exchange chromatography. Although the initial
      steps of the in vivo mechanism responsible for phosphorylation of potato starch
      remains elusive, the present study demonstrates that the enzyme machinery
      available in potato has the ability to incorporate phosphorylated alpha(1-
      >4)glucans into neutral polysaccharides in an interchain catalytic reaction.
      Potato mini tubers synthesized phosphorylated starch from exogenously supplied
      33PO43- and [U-14C]Glc at rates 4 times higher than those previously obtained
      using tubers from fully grown potato plants. This system was more reproducible
      compared with soil-grown tubers and was therefore used for preparation of 33P
      labeled phosphorylated alpha(1-->4)glucan chains.

PMID- 9662530
TI  - Isolation and characterization of glutathione S-transferase isozymes from
      sorghum.
AB  - Two glutathione S-transferase (GST) isozymes, A1/A1 and B1/B2, were purified from
      etiolated, O-1,3-dioxolan-2-yl-methyl-2,2,2, -trifluoro-4'-chloroacetophenone
      oxime-treated sorghum (Sorghum bicolor L. Moench) shoots. GST A1/A1, a
      constitutively expressed homodimer, had a subunit molecular mass of 26 kD and an
      isoelectric point of 4.9. GST A1/A1 exhibited high activity with 1-chloro-2, 4,
      dinitrobenzene (CDNB) but low activity with the chloroacetanilide herbicide
      metolachlor. For GST A1/A1, the random, rapid-equilibrium bireactant kinetic
      model provided a good description of the kinetic data for the substrates CDNB and
      glutathione (GSH). GST B1/B2 was a heterodimer with subunit molecular masses of
      26 kD (designated the B1 subunit) and 28 kD (designated the B2 subunit) and a
      native isoelectric point of 4.8. GST B1/B2 exhibited low activity with CDNB and
      high activity with metolachlor as the substrate. The kinetics of GST B1/B2
      activity with GSH and metolachlor fit a model describing a multisite enzyme
      having two binding sites with different affinities for these substrates. Both GST
      A1/A1 and GST B1/B2 exhibited GSH-conjugating activity with ethacrynic acid and
      GSH peroxidase activity with cumene hydroperoxide, 9-hydroperoxy-trans-10, cis-12
      octadecadienoic acid and 13-hydroperoxy-cis-9, trans-11-octadecadienoic acid.
      Both GST A1/A1 and GST B1/B2 are glycoproteins, as indicated by their binding of
      concanavalin A. Polyclonal antibodies raised against GST A1/A1 exhibited cross
      reactivity with the B1 subunit of GST B1/B2. Comparisons of the N-terminal amino
      acid sequences of the GST A1, B1, and B2 subunits with other type I theta-GSTs
      indicated a high degree of homology with the maize GST I subunit and a sugarcane
      GST.

PMID- 9662531
TI  - Autonomic straightening after gravitropic curvature of cress roots.
AB  - Few studies have documented the response of gravitropically curved organs to a
      withdrawal of a constant gravitational stimulus. The effects of stimulus
      withdrawal on gravitropic curvature were studied by following individual roots of
      cress (Lepidium sativum L.) through reorientation and clinostat rotation. Roots
      turned to the horizontal curved down 62 degrees and 88 degrees after 1 and 5 h,
      respectively. Subsequent rotation on a clinostat for 6 h resulted in root
      straightening through a loss of gravitropic curvature in older regions and
      through new growth becoming aligned closer to the prestimulus vertical. However,
      these roots did not return completely to the prestimulus vertical, indicating the
      retention of some gravitropic response. Clinostat rotation shifted the mean root
      angle -36 degrees closer to the prestimulus vertical, regardless of the duration
      of prior horizontal stimulation. Control roots (no horizontal stimulation) were
      slanted at various angles after clinostat rotation. These findings indicate that
      gravitropic curvature is not necessarily permanent, and that the root retains
      some commitment to its equilibrium orientation prior to gravitropic stimulation.

PMID- 9662532
TI  - Biosynthesis of the monoterpenes limonene and carvone in the fruit of caraway. I.
      Demonstration Of enzyme activities and their changes with development 
AB  - The biosynthesis of the monoterpenes limonene and carvone in the fruit of caraway
      (Carum carvi L.) proceeds from geranyl diphosphate via a three-step pathway.
      First, geranyl diphosphate is cyclized to (+)-limonene by a monoterpene synthase.
      Second, this intermediate is stored in the essential oil ducts without further
      metabolism or is converted by limonene-6-hydroxylase to (+)-trans-carveol. Third,
      (+)-trans-carveol is oxidized by a dehydrogenase to (+)-carvone. To investigate
      the regulation of monoterpene formation in caraway, we measured the time course
      of limonene and carvone accumulation during fruit development and compared it
      with monoterpene biosynthesis from [U-14C]Suc and the changes in the activities
      of the three enzymes. The activities of the enzymes explain the profiles of
      monoterpene accumulation quite well, with limonene-6-hydroxylase playing a
      pivotal role in controlling the nature of the end product. In the youngest
      stages, when limonene-6-hydroxylase is undetectable, only limonene was
      accumulating in appreciable levels. The appearance of limonene-6-hydroxylase
      correlates closely with the onset of carvone accumulation. At later stages of
      fruit development, the activities of all three enzymes declined to low levels.
      Although this correlates closely with a decrease in monoterpene accumulation, the
      latter may also be the result of competition with other pathways for substrate.

PMID- 9662533
TI  - Dehydration-stress-regulated transgene expression in stably transformed rice
      plants 
AB  - To confer abscisic acid (ABA) and/or stress-inducible gene expression, an ABA
      response complex (ABRC1) from the barley (Hordeum vulgare L.) HVA22 gene was
      fused to four different lengths of the 5' region from the rice (Oryza sativa L.)
      Act1 gene. Transient assay of beta-glucuronidase (GUS) activity in barley
      aleurone cells shows that, coupled with ABRC1, the shortest minimal promoter
      (Act1-100P) gives both the greatest induction and the highest level of absolute
      activity following ABA treatment. Two plasmids with one or four copies of ABRC1
      combined with the same Act1-100P and HVA22(I) of barley HVA22 were constructed
      and used for stable expression of uidA in transgenic rice plants. Three Southern
      blot-positive lines with the correct hybridization pattern for each construct
      were obtained. Northern analysis indicated that uidA expression is induced by
      ABA, water-deficit, and NaCl treatments. GUS activity assays in the transgenic
      plants confirmed that the induction of GUS activity varies from 3- to 8-fold with
      different treatments or in different rice tissues, and that transgenic rice
      plants harboring four copies of ABRC1 show 50% to 200% higher absolute GUS
      activity both before and after treatments than those with one copy of ABRC1.

PMID- 9662534
TI  - A new class of Arabidopsis mutants with reduced hexadecatrienoic acid fatty acid
      levels.
AB  - Chloroplast glycerolipids in a number of higher-plant species, including
      Arabidopsis thaliana, are synthesized by two distinct pathways termed the
      prokaryotic and eukaryotic pathways. The molecules of galactolipids produced by
      the prokaryotic pathway contain substantial amounts of hexadecatrienoic acid
      fatty acid. Here we describe a new class of mutants, designated gly1, with
      reduced levels of hexadecatrienoic acid. Lipid fatty acid profiles indicated that
      gly1 mutants exhibited a reduced carbon flux through the prokaryotic pathway that
      was compensated for by an increased carbon flux through the eukaryotic pathway.
      Genetic and biochemical approaches revealed that the gly1 phenotype could not be
      explained by a deficiency in the enzymes of the prokaryotic pathway. The flux of
      fatty acids into the prokaryotic pathway is sensitive to changes in glycerol-3
      phosphate (G3P) availability, and the chloroplast G3P pool can be increased by
      exogenous application of glycerol to leaves. Exogenous glycerol treatment of gly1
      plants allowed chemical complementation of the mutant phenotype. These results
      are consistent with a mutant lesion affecting the G3P supply within the
      chloroplast. The gly1 mutants may therefore help in determining the pathway for
      synthesis of chloroplast G3P.

PMID- 9662535
TI  - Transport of sterols to the plasma membrane of leek seedlings 
AB  - To investigate the intracellular transport of sterols in etiolated leek (Allium
      porrum L.) seedlings, in vivo pulse-chase experiments with [1-14C]acetate were
      performed. Then, endoplasmic reticulum-, Golgi-, and plasma membrane (PM)
      enriched fractions were prepared and analyzed for the radioactivity incorporated
      into free sterols. In leek seedlings sterols are present as a mixture in which
      (24R)-24-ethylcholest-5-en-3beta-ol is by far the major compound (around 60%).
      The other sterols are represented by cholest-5-en-3beta-ol, 24-methyl-cholest-5
      en-3beta-ol, (24S)-24-ethylcholesta-5,22E-dien-3beta-ol, and stigmasta-5,
      24(24(1))Z-dien-3beta-ol. These compounds are shown to reside mainly in the PM.
      Our results clearly indicate that free sterols are actively transported from the
      endoplasmic reticulum to the PM during the first 60 min of chase, with kinetics
      very similar to that of phosphatidylserine. Such a transport was found to be
      decreased at low temperature (12 degreesC) and following treatment with monensin
      and brefeldin A. These data are consistent with a membrane-mediated process for
      the intracellular transport of sterols to the PM, which likely involves the Golgi
      apparatus.

PMID- 9662536
TI  - Eucalypt NADP-dependent isocitrate dehydrogenase. cDNA cloning and expression in
      ectomycorrhizae.
AB  - NADP-dependent isocitrate dehydrogenase (NADP-ICDH) activity is increased in
      roots of Eucalyptus globulus subsp. bicostata ex Maiden Kirkp. during
      colonization by the ectomycorrhizal fungus Pisolithus tinctorius Coker and Couch.
      To investigate the regulation of the enzyme expression, a cDNA (EgIcdh) encoding
      the NADP-ICDH was isolated from a cDNA library of E. globulus-P. tinctorius
      ectomycorrhizae. The putative polypeptide sequence of EgIcdh showed a high amino
      acid similarity with plant NADP-ICDHs. Because the deduced EgICDH protein lacks
      an amino-terminal targeting sequence and shows highest similarity to plant
      cytosolic ICDHs, it probably represents a cytoplasmic isoform. RNA analysis
      showed that the steady-state level of EgIcdh transcripts was enhanced nearly 2
      fold in ectomycorrhizal roots compared with nonmycorrhizal roots. Increased
      accumulation of NADP-ICDH transcripts occurred as early as 2 d after contact and
      likely led to the observed increased enzyme activity. Indirect immunofluorescence
      microscopy indicated that NADP-ICDH was preferentially accumulated in the
      epidermis and stele parenchyma of nonmycorrhizal and ectomycorrhizal lateral
      roots. The putative role of cytosolic NADP-ICDH in ectomycorrhizae is discussed.

PMID- 9662537
TI  - Phosphoglycerylethanolamine posttranslational modification of plant eukaryotic
      elongation factor 1alpha.
AB  - Eukaryotic elongation factor 1alpha (eEF-1A) is a multifunctional protein. There
      are three known posttranslational modifications of eEF-1A that could potentially
      affect its function. Except for phosphorylation, the other posttranslational
      modifications have not been demonstrated in plants. Using matrix-assisted laser
      desorption/ionization-mass spectrometry and peptide mass mapping, we show that
      carrot (Daucus carota L.) eEF-1A contains a phosphoglycerylethanolamine (PGE)
      posttranslational modification. eEF-1A was the only protein labeled with
      [14C]ethanolamine in carrot cells and was the predominant ethanolamine-labeled
      protein in Arabidopsis seedlings and tobacco (Nicotiana tabacum L.) cell
      cultures. In vivo-labeling studies using [3H]glycerol, [32P]Pi, [14C]myristic
      acid, and [14C]linoleic acid indicated that the entire phospholipid
      phosphatidylethanolamine is covalently attached to the protein. The PGE lipid
      modification did not affect the partitioning of eEF-1A in Triton X-114 or its
      actin-binding activity in in vitro assays. Our in vitro data indicate that this
      newly characterized posttranslational modification alone does not affect the
      function of eEF-1A. Therefore, the PGE lipid modification may work in combination
      with other posttranslational modifications to affect the distribution and the
      function of eEF-1A within the cell.

PMID- 9662538
TI  - Implications of a developmental-stage-dependent thylakoid-bound protease in the
      stabilization of the light-harvesting pigment-protein complex serving photosystem
      II during thylakoid biogenesis in red kidney bean 
AB  - Intact etioplasts of bean (Phaseolus vulgaris) plants exhibit proteolytic
      activity against the exogenously added apoprotein of the light-harvesting pigment
      protein complex serving photosystem II (LHCII) that increases as etiolation is
      prolonged. The activity increases in the membrane fraction but not in the stroma,
      where it remains low and constant and is mainly directed against LHCII and
      protochlorophyllide oxidoreductase. The thylakoid proteolytic activity, which is
      low in etioplasts of 6-d-old etiolated plants, increases in plants pretreated
      with a pulse of light or exposed to intermittent-light (ImL) cycles, but
      decreases during prolonged exposure to continuous light, coincident with
      chlorophyll (Chl) accumulation. To distinguish between the control of Chl and/or
      development on proteolytic activity, we used plants exposed to ImL cycles of
      varying dark-phase durations. In ImL plants exposed to an equal number of ImL
      cycles with short or long dark intervals (i.e. equal Chl accumulation but
      different developmental stage) proteolytic activity increased with the duration
      of the dark phase. In plants exposed to ImL for equal durations to such light
      dark cycles (i.e. different Chl accumulation but same developmental stage) the
      proteolytic activity was similar. These results suggest that the protease, which
      is free to act under limited Chl accumulation, is dependent on the developmental
      stage of the chloroplast, and give a clue as to why plants in ImL with short dark
      intervals contain LHCII, whereas those with long dark intervals possess only
      photosystem-unit cores and lack LHCII.

PMID- 9662539
TI  - Characterization of spermidine binding to solubilized plasma membrane proteins
      from zucchini hypocotyls 
AB  - In this work [14C]spermidine binding to total proteins solubilized from plasma
      membrane purified from zucchini (Cucurbita pepo L.) hypocotyls was investigated.
      Proteins were solubilized using octyl glucoside as a detergent. Specific
      polyamine binding was thermolabile, reversible, pH dependent with an optimum at
      pH 8.0, and had a Kd value of 5 &mgr;M, as determined by glass-fiber-filter
      assays. Sephadex G-25 M gel-filtration assays confirmed the presence of a
      spermidine-protein(s) complex with a specific binding activity. By sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis and native polyacrylamide gel
      electrophoresis of collected fractions having the highest specific spermidine
      binding activity, several protein bands (113, 75, 66, and 44 kD) were identified.
      The specificity of spermidine binding was examined by gel-filtration competition
      experiments performed using other polyamines and compounds structurally related
      to spermidine. Partial purification on Sephadex G-200 led to the identification
      of 66- and 44-kD protein bands, which may represent the putative spermidine
      binding protein(s) on the plasmalemma.

PMID- 9662540
TI  - (+)-Abscisic acid metabolism, 3-ketoacyl-coenzyme A synthase gene expression, and
      very-long-chain monounsaturated fatty acid biosynthesis in brassica napus embryos
AB  - Microspore-derived embryos of Brassica napus cv Reston were used to examine the
      effects of exogenous (+)-abscisic acid (ABA) and related compounds on the
      accumulation of very-long-chain monounsaturated fatty acids (VLCMFAs), VLCMFA
      elongase complex activity, and induction of the 3-ketoacyl-coenzyme A synthase
      (KCS) gene encoding the condensing enzyme of the VLCMFA elongation system. Of the
      concentrations tested, (+)-ABA at 10 &mgr;M showed the strongest effect. Maximum
      activity of the elongase complex, observed 6 h after 10 &mgr;M (+)-ABA treatment,
      was 60% higher than that of the untreated embryos at 24 h. The transcript of the
      KCS gene was induced by 10 &mgr;M (+)-ABA within 1 h and further increased up to
      6 h. The VLCMFAs eicosenoic acid (20:1) and erucoic acid (22:1) increased by 1.5-
      to 2-fold in embryos treated with (+)-ABA for 72 h. Also, (+)-8'-methylene ABA,
      which is metabolized more slowly than ABA, had a stronger ABA-like effect on the
      KCS gene transcription, elongase complex activity (28% higher), and level of
      VLCMFAs (25-30% higher) than ABA. After 24 h approximately 60% of the added (+)
      [3H]ABA (10 &mgr;M) was metabolized, yielding labeled phaseic and dihydrophaseic
      acid. This study demonstrates that (+)-ABA promotes VLCMFA biosynthesis via
      increased expression of the KCS gene and that reducing ABA catabolism would
      increase VLCMFAs in microspore-derived embryos.

PMID- 9662541
TI  - Mutagenesis of the glucose-1-phosphate-binding site of potato tuber ADP-glucose
      pyrophosphorylase 
AB  - Lysine (Lys)-195 in the homotetrameric ADP-glucose pyrophosphorylase (ADPGlc
      PPase) from Escherichia coli was shown previously to be involved in the binding
      of the substrate glucose-1-phosphate (Glc-1-P). This residue is highly conserved
      in the ADPGlc PPase family. Site-directed mutagenesis was used to investigate the
      function of this conserved Lys residue in the large and small subunits of the
      heterotetrameric potato (Solanum tuberosum) tuber enzyme. The apparent affinity
      for Glc-1-P of the wild-type enzyme decreased 135- to 550-fold by changing Lys
      198 of the small subunit to arginine, alanine, or glutamic acid, suggesting that
      both the charge and the size of this residue influence Glc-1-P binding. These
      mutations had little effect on the kinetic constants for the other substrates
      (ATP and Mg2+ or ADP-Glc and inorganic phosphate), activator (3
      phosphoglycerate), inhibitor (inorganic phosphate), or on the thermal stability.
      Mutagenesis of the corresponding Lys (Lys-213) in the large subunit had no effect
      on the apparent affinity for Glc-1-P by substitution with arginine, alanine, or
      glutamic acid. A double mutant, SK198RLK213R, was also obtained that had a 100
      fold reduction of the apparent affinity for Glc-1-P. The data indicate that Lys
      198 in the small subunit is directly involved in the binding of Glc-1-P, whereas
      they appear to exclude a direct role of Lys-213 in the large subunit in the
      interaction with this substrate.

PMID- 9662542
TI  - Molecular and biochemical characterization of cytosolic phosphoglucomutase in
      maize. Expression during development and in response to oxygen deprivation.
AB  - Phosphoglucomutase (PGM) catalyzes the interconversion of glucose (Glc)-1- and
      Glc-6-phosphate in the synthesis and consumption of sucrose. We isolated two
      maize (Zea mays L.) cDNAs that encode PGM with 98.5% identity in their deduced
      amino acid sequence. Southern-blot analysis with genomic DNA from lines with
      different Pgm1 and Pgm2 genotypes suggested that the cDNAs encode the two known
      cytosolic PGM isozymes, PGM1 and PGM2. The cytosolic PGMs of maize are distinct
      from a plastidic PGM of spinach (Spinacia oleracea). The deduced amino acid
      sequences of the cytosolic PGMs contain the conserved phosphate-transfer
      catalytic center and the metal-ion-binding site of known prokaryotic and
      eukaryotic PGMs. PGM mRNA was detectable by RNA-blot analysis in all tissues and
      organs examined except silk. A reduction in PGM mRNA accumulation was detected in
      roots deprived of O2 for 24 h, along with reduced synthesis of a PGM identified
      as a 67-kD phosphoprotein on two-dimensional gels. Therefore, PGM is not one of
      the so-called "anaerobic polypeptides." Nevertheless, the specific activity of
      PGM was not significantly affected in roots deprived of O2 for 24 h. We propose
      that PGM is a stable protein and that existing levels are sufficient to maintain
      the flux of Glc-1-phosphate into glycolysis under O2 deprivation.

PMID- 9662543
TI  - Metabolism of uridine 5'-diphosphate-glucose in golgi vesicles from pea stems 
AB  - Uridine 5'-diphosphate-glucose (UDP-Glc) is transported into the lumen of the
      Golgi cisternae, where is used for polysaccharide biosynthesis. When Golgi
      vesicles were incubated with UDP-[3H]Glc, [3H]Glc was rapidly transferred to
      endogenous acceptors and UDP-Glc was undetectable in Golgi vesicles. This result
      indicated that a uridine-containing nucleotide was rapidly formed in the Golgi
      vesicles. Since little is known about the fate of the nucleotide derived from UDP
      Glc, we analyzed the metabolism of the nucleotide moiety of UDP-Glc by incubating
      Golgi vesicles with [alpha-32P]UDP-Glc, [beta-32P]UDP-Glc, and [3H]UDP-Glc and
      identifying the resulting products. After incubation of Golgi vesicles with these
      radiolabeled substrates we could detect only uridine 5'-monophosphate (UMP) and
      inorganic phosphate (Pi). UDP could not be detected, suggesting a rapid
      hydrolysis of UDP by the Golgi UDPase. The by-products of UDP hydrolysis, UMP and
      Pi, did not accumulate in the lumen, indicating that they were able to exit the
      Golgi lumen. The exit of UMP was stimulated by UDP-Glc, suggesting the presence
      of a putative UDP-Glc/UMP antiporter in the Golgi membrane. However, the exit of
      Pi was not stimulated by UDP-Glc, suggesting that the exit of Pi occurs via an
      independent membrane transporter.

PMID- 9662544
TI  - Multiple genes encoding the conserved CCAAT-box transcription factor complex are
      expressed in Arabidopsis.
AB  - The CCAAT motif is found in the promoters of many eukaryotic genes. In yeast a
      single complex of three proteins, termed HAP2, HAP3, and HAP5, binds to this
      sequence, and in mammals the three components of the equivalent complex (called
      variously NF-Y, CBF, or CP1) are also represented by single genes. Here we report
      the presence of multiple genes for each of the components of the CCAAT-binding
      complex, HAP2, 3,5, from Arabidopsis. Three independent Arabidopsis HAP subunit 2
      (AtHAP2) cDNAs were cloned by functional complementation of a yeast hap2 mutant,
      and two independent forms each of AtHAP3 and AtHAP5 cDNAs were detected in the
      expressed sequence tag database. Additional homologs (two of AtHAP3 and one of
      AtHAP5) have been identified from available Arabidopsis genomic sequences.
      Northern-blot analysis indicated ubiquitous expression for each AtHAP2 and AtHAP5
      cDNA in a range of tissues, whereas expression of each AtHAP3 cDNA was under
      developmental and/or environmental regulation. The unexpected presence of
      multiple forms of each HAP homolog in Arabidopsis, compared with the single genes
      in yeast and vertebrates, suggests that the HAP2,3,5 complex may play diverse
      roles in gene transcription in higher plants.

PMID- 9662545
TI  - Second messengers mediate increases in cytosolic calcium in tobacco protoplasts 
AB  - Addition of membrane-permeable cyclic GMP (cGMP) and cyclic AMP (cAMP) were shown
      to cause elevation of cytosolic Ca2+ concentration ([Ca2+]cyt) in tobacco
      (Nicotiana plumbaginofolia) protoplasts. Under the same conditions these cyclic
      nucleotides were shown to provoke a physiological swelling response in the
      protoplasts. Nonmembrane-permeable cAMP and cGMP were unable to trigger a
      detectable [Ca2+]cyt response. Cyclic-nucleotide-mediated elevations in [Ca2+]cyt
      involved both internal and external Ca2+ stores. Both cAMP- and cGMP-mediated
      [Ca2+]cyt elevations could be inhibited by the Ca2+-channel blocker verapamil.
      Addition of inhibitors of phosphodiesterases (isobutylmethylxanthine and
      zaprinast) and the adenylate cyclase agonist forskolin to the protoplasts
      (predicted to elevate in vivo cyclic-nucleotide concentrations) caused elevations
      in [Ca2+]cyt. Addition of the adenylate cyclase inhibitor 2', 5'-dideoxyadenosine
      before forskolin significantly inhibited the forskolin-induced [Ca2+]cyt
      elevation. Taken together, these data suggest that a potential communication
      point for cross-talk between signal transduction pathways using cyclic
      nucleotides in plants is at the level of Ca2+ signaling.

PMID- 9662546
TI  - Systemin potentiates the oxidative burst in cultured tomato cells 
AB  - Plants that have been wounded by insects or other herbivores may be more
      susceptible to infection by adventitious microbes. Wound-induced signal
      molecules, which serve to induce responses in the plant that retard further
      feeding, might also act to prepare a plant for possible pathogen attack. We have
      examined the effect of a wound-generated systemic messenger (systemin) on a
      pathogen-stimulated defense-response marker, the oxidative burst. We observed
      that neither systemin nor its inactive analog (A-17) was able to directly induce
      H2O2 biosynthesis in suspension-cultured tomato (Lycopersicon esculentum L.)
      cells, regardless of the duration of exposure of the cells to the two peptides.
      Similarly, neither systemin nor A-17 was capable of modifying an
      oligogalacturonide-elicited oxidative burst, as long as elicitor addition
      occurred within minutes of treatment with systemin or A-17. In contrast,
      preexposure of the cell cultures to systemin (but not to A-17) led to a time
      dependent enhancement of the oligogalacturonide-elicited oxidative burst. By 12 h
      of exposure, the H2O2 biosynthetic capacity of systemin-treated cells exceeded
      that of the control cells by a factor of 16 +/- 2. A similar up-regulation by
      systemin of a mechanically stimulated oxidative burst was also observed. Because
      the systemin-induced augmentation in oxidant synthesis is quantitatively
      prevented by coincubation with 2 &mgr;M cycloheximide, and because the oxidative
      burst of oligogalacturonic acid-elicited control cells (no systemin exposure) is
      unaffected by preincubation with cycloheximide, we conclude that systemin
      enhancement of the tomato-cell oxidative burst requires protein synthesis.

PMID- 9662547
TI  - Does leaf position within a canopy affect acclimation of photosynthesis to
      elevated CO2?. Analysis Of a wheat crop under free-air co2 enrichment 
AB  - Previous studies of photosynthetic acclimation to elevated CO2 have focused on
      the most recently expanded, sunlit leaves in the canopy. We examined acclimation
      in a vertical profile of leaves through a canopy of wheat (Triticum aestivum L.).
      The crop was grown at an elevated CO2 partial pressure of 55 Pa within a
      replicated field experiment using free-air CO2 enrichment. Gas exchange was used
      to estimate in vivo carboxylation capacity and the maximum rate of ribulose-1,5
      bisphosphate-limited photosynthesis. Net photosynthetic CO2 uptake was measured
      for leaves in situ within the canopy. Leaf contents of ribulose-1,5-bisphosphate
      carboxylase/oxygenase (Rubisco), light-harvesting-complex (LHC) proteins, and
      total N were determined. Elevated CO2 did not affect carboxylation capacity in
      the most recently expanded leaves but led to a decrease in lower, shaded leaves
      during grain development. Despite this acclimation, in situ photosynthetic CO2
      uptake remained higher under elevated CO2. Acclimation at elevated CO2 was
      accompanied by decreases in both Rubisco and total leaf N contents and an
      increase in LHC content. Elevated CO2 led to a larger increase in LHC/Rubisco in
      lower canopy leaves than in the uppermost leaf. Acclimation of leaf
      photosynthesis to elevated CO2 therefore depended on both vertical position
      within the canopy and the developmental stage.

PMID- 9662548
TI  - Genetic manipulation of alcohol dehydrogenase levels in ripening tomato fruit
      affects the balance of some flavor aldehydes and alcohols 
AB  - Tomato (Lycopersicon esculentum) plants were transformed with gene constructs
      containing a tomato alcohol dehydrogenase (ADH) cDNA (ADH 2) coupled in a sense
      orientation with either the constitutive cauliflower mosaic virus 35S promoter or
      the fruit-specific tomato polygalacturonase promoter. Ripening fruit from plants
      transformed with the constitutively expressed transgene(s) had a range of ADH
      activities; some plants had no detectable activity, whereas others had
      significantly higher ADH activity, up to twice that of controls. Transformed
      plants with fruit-specific expression of the transgene(s) also displayed a range
      of enhanced ADH activities in the ripening fruit, but no suppression was
      observed. Modified ADH levels in the ripening fruit influenced the balance
      between some of the aldehydes and the corresponding alcohols associated with
      flavor production. Hexanol and Z-3-hexenol levels were increased in fruit with
      increased ADH activity and reduced in fruit with low ADH activity. Concentrations
      of the respective aldehydes were generally unaltered. The phenotypes of modified
      fruit ADH activity and volatile abundance were transmitted to second-generation
      plants in accordance with the patterns of inheritance of the transgenes. In a
      preliminary taste trial, fruit with elevated ADH activity and higher levels of
      alcohols were identified as having a more intense "ripe fruit" flavor.

PMID- 9662549
TI  - Potent inhibition of ribulose-bisphosphate carboxylase by an oxidized impurity in
      ribulose-1,5-bisphosphate 
AB  - Oxidation of D-ribulose-1,5-bisphosphate (ribulose-P2) during synthesis and/or
      storage produces D-glycero-2,3-pentodiulose-1, 5-bisphosphate (pentodiulose-P2),
      a potent slow, tight-binding inhibitor of spinach (Spinacia oleracea L.) ribulose
      P2 carboxylase/oxygenase (Rubisco). Differing degrees of contamination with
      pentodiulose-P2 caused the decline in Rubisco activity seen during Rubisco assay
      time courses to vary between different preparations of ribulose-P2. With some
      ribulose-P2 preparations, this compound can be the dominant cause of the decline,
      far exceeding the significance of the catalytic by-product, D-xylulose-1, 5
      bisphosphate. Unlike xylulose-1,5-bisphosphate, pentodiulose-P2 did not appear to
      be a significant by-product of catalysis by wild-type Rubisco at saturating CO2
      concentration. It was produced slowly during frozen storage of ribulose-P2, even
      at low pH, more rapidly in Rubisco assay buffers at room temperature, and
      particularly rapidly on deliberate oxidation of ribulose-P2 with Cu2+. Its
      formation was prevented by the exclusion of transition metals and O2.
      Pentodiulose-P2 was unstable and decayed to a variety of other less-inhibitory
      compounds, particularly in the presence of some buffers. However, it formed a
      tight, stable complex with carbamylated spinach Rubisco, which could be isolated
      by gel filtration, presumably because its structure mimics that of the enediol
      intermediate of Rubisco catalysis. Rubisco catalyzes the cleavage of pentodiulose
      P2 by H2O2, producing P-glycolate.

PMID- 9662550
TI  - Expression of tobacco carbonic anhydrase in the C4 dicot flaveria bidentis leads
      to increased leakiness of the bundle sheath and a defective CO2-concentrating
      mechanism 
AB  - Flaveria bidentis (L.) Kuntze, a C4 dicot, was genetically transformed with a
      construct encoding the mature form of tobacco (Nicotiana tabacum L.) carbonic
      anhydrase (CA) under the control of a strong constitutive promoter. Expression of
      the tobacco CA was detected in transformant whole-leaf and bundle-sheath cell
      (bsc) extracts by immunoblot analysis. Whole-leaf extracts from two CA
      transformed lines demonstrated 10% to 50% more CA activity on a ribulose-1,5
      bisphosphate carboxylase/oxygenase-site basis than the extracts from transformed,
      nonexpressing control plants, whereas 3 to 5 times more activity was measured in
      CA transformant bsc extracts. This increased CA activity resulted in plants with
      moderately reduced rates of CO2 assimilation (A) and an appreciable increase in C
      isotope discrimination compared with the controls. With increasing O2
      concentrations up to 40% (v/v), a greater inhibition of A was found for
      transformants than for wild-type plants; however, the quantum yield of
      photosystem II did not differ appreciably between these two groups over the O2
      levels tested. The quantum yield of photosystem II-to-A ratio suggested that at
      higher O2 concentrations, the transformants had increased rates of
      photorespiration. Thus, the expression of active tobacco CA in the cytosol of F.
      bidentis bsc and mesophyll cells perturbed the C4 CO2-concentrating mechanism by
      increasing the permeability of the bsc to inorganic C and, thereby, decreasing
      the availability of CO2 for photosynthetic assimilation by ribulose-1,5
      bisphosphate carboxylase/oxygenase.

PMID- 9662551
TI  - Analysis of respiratory chain regulation in roots of soybean seedlings 
AB  - Changes in the respiratory rate and the contribution of the cytochrome (Cyt) c
      oxidase and alternative oxidase (COX and AOX, respectively) were investigated in
      soybean (Glycine max L. cv Stevens) root seedlings using the 18O-discrimination
      method. In 4-d-old roots respiration proceeded almost entirely via COX, but by d
      17 more than 50% of the flux occurred via AOX. During this period the capacity of
      COX, the theoretical yield of ATP synthesis, and the root relative growth rate
      all decreased substantially. In extracts from whole roots of different ages, the
      ubiquinone pool was maintained at 50% to 60% reduction, whereas pyruvate content
      fluctuated without a consistent trend. In whole-root immunoblots, AOX protein was
      largely in the reduced, active form at 7 and 17 d but was partially oxidized at 4
      d. In isolated mitochondria, Cyt pathway and succinate dehydrogenase capacities
      and COX I protein abundance decreased with root age, whereas both AOX capacity
      and protein abundance remained unchanged. The amount of mitochondrial protein on
      a dry-mass basis did not vary significantly with root age. It is concluded that
      decreases in whole-root respiration during growth of soybean seedlings can be
      largely explained by decreases in maximal rates of electron transport via COX.
      Flux via AOX is increased so that the ubiquinone pool is maintained in a
      moderately reduced state.

PMID- 9662552
TI  - The biosynthesis of salicylic acid in potato plants 
AB  - Spraying potato (Solanum tuberosum L.) leaves with arachidonic acid (AA) at 1500
      &mgr;g mL-1 led to a rapid local synthesis of salicylic acid (SA) and
      accumulation of a SA conjugate, which was shown to be 2-O-beta
      glucopyranosylsalicylic acid. Radiolabeling studies with untreated leaves showed
      that SA was synthesized from phenylalanine and that both cinnamic and benzoic
      acid were intermediates in the biosynthesis pathway. Using radiolabeled
      phenylalanine as a precursor, the specific activity of SA was found to be lower
      when leaves were treated with AA than in control leaves. Similar results were
      obtained when leaves were fed with the labeled putative intermediates cinnamic
      acid and benzoic acid. Application of 2-aminoindan-2-phosphonic acid at 40
      &mgr;M, an inhibitor of phenylalanine ammonia-lyase, prior to treatment with AA
      inhibited the local accumulation of SA. When the putative intermediates were
      applied to leaves in the presence of 2-aminoindan-2-phosphonic acid, about 40% of
      the expected accumulation of free SA was recovered, but the amount of the
      conjugate remained constant.

PMID- 9662553
TI  - Pathogen-induced changes in the antioxidant status of the apoplast in barley
      leaves 
AB  - Leaves of two barley (Hordeum vulgare L.) isolines, Alg-R, which has the dominant
      Mla1 allele conferring hypersensitive race-specific resistance to avirulent races
      of Blumeria graminis, and Alg-S, which has the recessive mla1 allele for
      susceptibility to attack, were inoculated with B. graminis f. sp. hordei. Total
      leaf and apoplastic antioxidants were measured 24 h after inoculation when
      maximum numbers of attacked cells showed hypersensitive death in Alg-R.
      Cytoplasmic contamination of the apoplastic extracts, judged by the marker enzyme
      glucose-6-phosphate dehydrogenase, was very low (less than 2%) even in inoculated
      plants. Dehydroascorbate, glutathione, superoxide dismutase, catalase, ascorbate
      peroxidase, glutathione reductase, monodehydroascorbate reductase, and
      dehydroascorbate reductase were present in the apoplast. Inoculation had no
      effect on the total foliar ascorbate pool size or the redox state. The
      glutathione content of Alg-S leaves and apoplast decreased, whereas that of Alg-R
      leaves and apoplast increased after pathogen attack, but the redox state was
      unchanged in both cases. Large increases in foliar catalase activity were
      observed in Alg-S but not in Alg-R leaves. Pathogen-induced increases in the
      apoplastic antioxidant enzyme activities were observed. We conclude that
      sustained oxidation does not occur and that differential strategies of
      antioxidant response in Alg-S and Alg-R may contribute to pathogen sensitivity.

PMID- 9662554
TI  - Detection of Ca2+-dependent transglutaminase activity in root and leaf tissue of
      monocotyledonous and dicotyledonous plants 
AB  - Protein extracted from root and leaf tissue of the dicotyledonous plants pea
      (Pisum sativum) and broad bean (Vicia faba) and the monocotyledonous plants wheat
      (Triticum aestivum) and barley (Hordeum vulgare) were shown to catalyze the
      incorporation of biotin-labeled cadaverine into microtiter-plate-bound N', N'
      dimethylcasein and the cross-linking of biotin-labeled casein to microtiter-plate
      bound casein in a Ca2+-dependent manner. The cross-linking of biotinylated casein
      and the incorporation of biotin-labeled cadaverine into N',N'-dimethylcasein were
      time-dependent reactions with a pH optimum of 7.9. Transglutaminase activity was
      shown to increase over a 2-week growth period in both the roots and leaves of
      pea. The product of transglutaminase's protein-cross-linking activity, epsilon
      (gamma-glutamyl)-lysine isodipeptide, was detected in root and shoot protein from
      pea, broad bean, wheat, and barley by cation-exchange chromatography. The
      presence of the isodipeptide was confirmed by reversed-phase chromatography.
      Hydrolysis of the isodipeptide after cation-exchange chromatography confirmed the
      presence of glutamate and lysine.

PMID- 9662555
TI  - Structure and origin of ordered lipid domains in biological membranes.

PMID- 9662556
TI  - Separate domains for desensitization of GABA rho 1 and beta 2 subunits expressed
      in Xenopus oocytes.
AB  - Desensitization of ligand-gated receptor channels is an intrinsic feedback
      mechanism and prevents the receptor/channels from becoming overly activated
      thereby maintaining biological function of the nervous system. Desensitization
      also plays an important role in neuronal plasticity. By taking advantage of
      biophysical and pharmacological diversities of GABA beta2 subunits from the brain
      and rho1 subunits from the retina, structural determinants that confer agonist
      induced desensitization were identified. A synthetic chimeric receptor/channel
      was created from the beta2 and rho1 subunits for this investigation. The chimera
      was constructed from the extracellular N-domain of the beta2 subunit, extending
      from the amino terminus to the beginning region of the M1 transmembrane segment,
      and from the C-domain of the rho1 subunit extending from the M1 transmembrane
      segment to the carboxyl terminus. The C-domain region included the M1 to M4
      transmembrane regions and the large intracellular loop between the M3 and M4
      transmembrane segments. Homo-oligomeric GABA beta2, rho1, and beta2/rho1 chimeric
      receptor/channels were individually expressed in Xenopus oocytes, and the
      desensitization characteristics attributable to each type of subunit were
      compared. Results from the present study reveal that motifs in the amino-terminal
      and carboxyl-terminal domains of the beta2 subunit conferred the agonist-induced
      desensitization; chloroform modulation was linked to specific phases of the GABA
      activated current decay.

PMID- 9662557
TI  - Characteristics of single, large-conductance calcium-dependent potassium channels
      (BKCa) from smooth muscle cells isolated from the rabbit mesenteric artery.
AB  - Smooth muscle cells isolated from the secondary and tertiary branches of the
      rabbit mesenteric artery contain large Ca2+-dependent channels. In excised
      patches with symmetrical (140 mm) K+ solutions, these channels had an average
      slope conductance of 235 +/- 3 pS, and reversed in direction at -6.1 +/- 0.4 mV.
      The channel showed K+ selectivity and its open probability (Po) was voltage
      dependent. Iberiotoxin (50 nm) reversibly decreased Po, whereas
      tetraethylammonium (TEA, at 1 mm) reduced the unitary current amplitude. Apamin
      (200 nm) had no effect. The channel displayed sublevels around 1/3 and 1/2 of the
      mainstate level. The effect of [Ca2+] on Po was studied and data fitted to
      Boltzmann relationships. In 0.1, 0.3, 1.0 and 10 microM Ca2+, V1/2 was 77.1 +/-
      5.3 (n = 18), 71.2 +/- 4.8 (n = 16), 47.3 +/- 10.1 (n = 11) and -14.9 +/- 10.1 mV
      (n = 6), respectively. Values of k obtained in 1 and 10 microM [Ca2+] were
      significantly larger than that observed in 0.1 microM [Ca2+]. With 30 microM NS
      1619 (a BKCa channel activator), V1/2 values were shifted by 39 mV to the left
      (hyperpolarizing direction) and k values were not affected. TEA applied
      intracellularly, reduced the unitary current amplitude with a Kd of 59 mm. In
      summary, BKCa channels show a particularly weak sensitivity to intracellular TEA
      and they also display large variation in V1/2 and k. These findings suggest the
      possibility that different types (isoforms) of BKCa channels may exist in this
      vascular tissue.

PMID- 9662558
TI  - Modulation of IA potassium current in adrenal cortical cells by a series of ten
      lanthanide elements.
AB  - The modulation of IA K+ current by ten trivalent lanthanide (Ln3+) cations
      spanning the series with ionic radii ranging from 0.99 A to 1.14 A was
      characterized by the whole-cell patch clamp technique in bovine adrenal zona
      fasciculata (AZF) cells. Each of the ten Ln3+s reduced IA amplitude measured at
      +20 mV in a concentration-dependent manner. Smaller Ln3+s were the most potent
      and half-maximally effective concentrations (EC50s) varied inversely with ionic
      radius for the larger elements. Estimation of EC50s yielded the following potency
      sequence: Lu3+ (EC50 = 3.0 microM) approximately Yb3+ (EC50 = 2.7 microM) > Er3+
      (EC50 = 3.7 microM) >/= Dy3+ (EC50 = 4.7 microM) > Gd3+ (EC50 = 6.7 microM)
      approximately Sm3+ (EC50 = 6.9 microM) > Nd3+ (EC50 = 11.2 microM) > Pr3+ (EC50 =
      22.3 microM) > Ce3+ (EC50 = 28.0 microM) > La3+ (EC50 = 33.7 microM). Ln3+s
      altered selected voltage-dependent gating and kinetic parameters of IA with a
      potency and order of effectiveness that paralleled the reduction of IA amplitude.
      Ln3+s markedly slowed activation kinetics and shifted the voltage-dependence of
      IA gating such that activation and steady-state inactivation occurred at more
      depolarized potentials. In contrast, Ln3+s did not measurably alter inactivation
      or deactivation kinetics and only slightly slowed kinetics of inactivated
      channels returning to the closed state. Replacement of external Ca2+ with Mg2+
      had no effect on the concentration-dependent inhibition of IA by Ln3+s. In
      contrast to their action on IA K+ current, Ln3+s inhibited T-type Ca2+ currents
      in AZF cells without slowing activation kinetics. These results indicate that
      Ln3+ modulate IA K+ channels through binding to a site on IA channels located
      within the electric field but which is not specific for Ca2+. They are consistent
      with a model where Ln3+ binding to negative charges on the gating apparatus
      alters the voltage-dependence and kinetics of channel opening. Ln3+s modulate
      transient K+ and Ca2+ currents by two fundamentally different mechanisms.

PMID- 9662559
TI  - Concurrent and independent HCO3- and Cl- secretion in a human pancreatic duct
      cell line (CAPAN-1).
AB  - The present study investigated both HCO-3 and Cl- secretions in a human
      pancreatic duct cell line, CAPAN-1, using the short-circuit current (Isc)
      technique. In Cl-/HCO-3-containing solution, secretin (1 microM) or forskolin (10
      microM) stimulated a biphasic rise in the Isc which initially reached a peak
      level at about 3 min and then decayed to a plateau level after 7 min. Removal of
      external Cl- abolished the initial transient phase in the forskolin-induced Isc
      while the plateau remained. In HCO-3/CO2-free solution, on the contrary, only the
      initial transient increase in Isc was prominent. Summation of the current
      magnitudes observed in Cl--free and HCO-3-free solutions over a time course of 10
      min gave rise to a curve which was similar, both in magnitude and kinetics, to
      the current observed in Cl-/HCO-3-containing solution. Removal of external Na+
      greatly reduced the initial transient rise in the forskolin-induced Isc response,
      and the plateau level observed under this condition was similar to that obtained
      in Cl--free solution, suggesting that Cl--dependent Isc was also Na+-dependent.
      Bumetanide (50 microM), an inhibitor of the Na+-K+-2Cl- cotransporter, and Ba2+
      (1 mm), a K+ channel blocker, could reduce the forskolin-induced Isc obtained in
      Cl-/HCO-3-containing or HCO-3-free solution. However, they were found to be
      ineffective when external Cl- was removed, indicating the involvement of these
      mechanisms in Cl- secretion. On the contrary, the HCO-3-dependent (in the absence
      of external Cl-) forskolin-induced Isc could be significantly reduced by carbonic
      anhydrase inhibitor, acetazolamide (45 microM). Basolateral application of
      amiloride (100 microM) inhibited the Isc; however, a specific Na+-H+ exchanger
      blocker, 5-N-methyl-N-isobutylamiloride (MIA, 5-10 microM) was found to be
      ineffective, excluding the involvement of the Na+-H+ exchanger. However, an
      inhibitor of H+-ATPase, N-ethylmaleimide did suppress the Isc (IC50 = 22 microM).
      Immunohistochemical studies also confirmed the presence of a vacuolar type of H+
      ATPase in these cells. H2DIDS (100 microM), an inhibitor of Na+-HCO-3
      cotransporter, was without effect. Apical addition of Cl- channel blocker,
      diphenylamine-2,2'-dicarboxylic acid (DPC, 1 mm), but not disulfonic acids, DIDS
      (100 microM) or SITS (100 microM), exerted an inhibitory effect on both Cl- and
      HCO-3-dependent forskolin-induced Isc responses. Histochemical studies showed
      discrete stainings of carbonic anhydrase in the monolayer of CAPAN-1 cells,
      suggesting that HCO-3 secretion may be specialized to a certain population of
      cells. The present results suggest that both HCO-3 and Cl- secretion by the human
      pancreatic duct cells may occur concurrently and independently.

PMID- 9662560
TI  - Membrane asymmetry in isolated canine cardiac sarcoplasmic reticulum: comparison
      with skeletal muscle sarcoplasmic reticulum.
AB  - Cardiac sarcoplasmic reticulum (CSR), isolated from dog hearts, was shown to be
      asymmetric in the distribution of phospholipids across the CSR bilayer.
      Phosphatidylethanolamine was mostly resident in the outer leaflet,
      phosphatidylcholine was equally distributed across both monolayers and
      phosphatidylserine was found primarily in the inner monolayer. This distribution
      of headgroups is similar to that found in fast skeletal muscle sarcoplasmic
      reticulum (SSR); however, the asymmetry in CSR is not as striking as that in SSR.
      Phospholipids retained by the CSR calcium pump protein (CaATPase) after detergent
      "stripping" were similar to those intimate to the SSR CaATPase, although the
      percentages of unsaturated phospholipids and plasmalogenic phospholipids are not
      as great as in the skeletal system. Lipids associated with the CSR CaATPase
      following DFDNB cross-linking showed a preference for retention of the
      aminophospholipids, again similar to the SSR CaATPase. Because the nonrandom
      distribution of membrane lipids modifies SSR function, it is likely these
      membrane lipids impact in situ the function of the CSR.

PMID- 9662561
TI  - Maturational changes in rabbit renal brush border membrane vesicle osmotic water
      permeability.
AB  - We have recently shown that the osmotic water permeability (Pf) of proximal
      tubules from neonatal rabbits is higher than that of adults (AJP 271:F871-F876,
      1996). The developmental change in Pf could be due to differences in one or more
      of the components in the path for transepithelial water transport. The present
      study examined developmental changes in water transport characteristics of the
      proximal tubule apical membrane by determining Pf and aquaporin 1 (AQP1)
      expression in neonatal (10-14 days old) and adult rabbit renal brush border
      membrane vesicles (BBMV). AQP1 abundance in the adult BBMV was higher than the
      neonatal BBMV. At 25 degrees C the Pf of neonatal BBMV was found to be
      significantly lower than the adult BBMV at osmotic gradients from 50 to 250
      mOsm/kg water. The activation energy for osmotic water movement was higher in the
      neonatal BBMV than the adult BBMV (9.19 +/- 0.37 vs. 5.09 +/- 0.57 kcal . deg-1 .
      mol-1, P < 0.005). Osmotic water movement in neonatal BBMV was inhibited 17.9 +/-
      1.3% by 1 mm HgCl2 compared to 34.3 +/- 3.8% in the adult BBMV (P < 0.005). These
      data are consistent with a significantly greater fraction of water traversing the
      apical membrane lipid bilayer in proximal tubules of neonates than adults. The
      lower Pf of the neonatal BBMV indicates that the apical membrane is not
      responsible for the higher transepithelial Pf in the neonatal proximal tubule.

PMID- 9662562
TI  - Identification of two essential arginine residues in UhpT, the sugar phosphate
      antiporter of Escherichia coli.
AB  - Three lines of evidence indicate that arginine-46 (R46) and arginine-275 (R275)
      are essential to the function of UhpT, the Pi-linked antiport protein of
      Escherichia coli. A role for arginine was initially suggested by the sensitivity
      of UhpT to inhibition by 2,3-butanedione, an arginine-directed probe. Since the
      presence of substrate protected against this inhibition, this work further
      suggested that arginine(s) may lie at or near the UhpT active site. In other
      work, each UhpT arginine was examined individually by using site-directed
      mutagenesis to generate a cysteine or a lysine derivative. With two exceptions
      (R46, R275), all arginines could be replaced by either cysteine (10 of 14
      residues) or lysine (12 of 14) without loss of function, implicating R46 and R275
      as essential to UhpT function. This idea was strengthened by examining a multiple
      alignment of the eleven known UhpT-related proteins (>/=30% identity). That
      alignment showed R46 and R275 were two of the only three arginines strongly
      conserved in this group of proteins. Considered together, these different
      approaches lead us to conclude that UhpT and its relatives have only two arginine
      residues (R46, R275) whose presence is essential to function. Prior biochemical
      work had placed R275 at the external entrance to the translocation pathway, and a
      symmetry argument emerging from the multiple alignment suggests a similar
      position for R46. Accordingly, by virtue of their locations at the entrance to
      this pathway, we speculate that R46 and R275 function in establishing substrate
      specificity.

PMID- 9662563
TI  - Potentiation by isoproterenol on carbachol-induced K+ and Cl- currents and fluid
      secretion in rat parotid.
AB  - Isoproterenol (IPR) and 8-(4-chlorophenylthio)-cyclic AMP (cpt-cAMP) enhanced
      carbachol (CCh)-induced fluid secretion from rat parotid glands, but had no
      effect by themselves. The enhancement by IPR was blocked by propranolol. In
      dispersed parotid acinar cells, IPR and cpt-cAMP potentiated CCh-induced K+ and
      Cl- currents (IK and ICl). IPR at the concentration of 0.1 microM significantly
      potentiated the CCh-induced increase in intracellular Ca2+ concentration
      ([Ca2+]i), but 1 mm cpt-cAMP did not. The incidence of the potentiation by IPR in
      CCh-induced Mn2+ entry was 31% and that by cpt-cAMP was 21%. The potentiation by
      IPR in the ionic currents and the [Ca2+]i was suppressed by propranolol. These
      results suggest that the CCh-induced fluid secretion from rat parotid glands is
      enhanced by IPR through the potentiation of IK and ICl mainly by the increased
      cyclic AMP level and partially by the potentiated Ca2+ influx and [Ca2+]i
      increase, and that IPR is more effective than cpt-cAMP in the enhancement of the
      CCh-induced [Ca2+]i increase.

PMID- 9662564
TI  - Cytotoxic T cells and immunotherapy.
AB  - Promising immunotherapies for viral infections and malignancies reflect the
      successful, rapid translation of laboratory findings into clinical practice.
      Fletcher et al. [1] present imaging studies of Epstein-Barr virus (EBV)
      associated lymphomas before and after immunotherapy. Here, we briefly review the
      scientific bases of such novel therapies, which have evolved from advances in
      understanding of immune effector cells, of the cytokines that drive immune
      responses, and of the mechanisms underlying cell death.

PMID- 9662565
TI  - Upper airway obstruction and pulmonary abnormalities due to lymphoproliferative
      disease following bone marrow transplantation in children.
AB  - We report three patients who developed severe supraglottic airway obstruction due
      to Epstein-Barr virus lymphoproliferative disease following allogeneic bone
      marrow transplantation. In addition to enlarged pharyngeal lymphoid tissue seen
      in all three patients, two had supraglottic airway narrowing and two developed
      pulmonary lymphoproliferative disease. They were treated with unmanipulated T
      cells or EBV-specific cytotoxic T lymphocytes. Life-threatening upper airway
      obstruction is a radiologically detectable complication of allogeneic bone marrow
      transplantation in children.

PMID- 9662566
TI  - Cervical spine abnormalities and instability with myelopathy in warfarin-related
      chondrodysplasia: 17-year follow-up.
AB  - A patient with warfarin embryopathy developed progressive cervical spinal
      myelopathy owing to bony cervical spinal damage. While there are several
      descriptions of warfarin embryopathy, the long-term complication of cervical
      spinal instability has not been reported. This cervical instability may, as in
      our patient, cause severe neurological dysfunction or even sudden death;
      therefore, it is important that pediatric radiologists should be alert to this
      condition.

PMID- 9662567
TI  - Fibrous tumours in children: imaging features of a heterogeneous group of
      disorders.
AB  - BACKGROUND: Fibrous tumours are predominantly soft tissue lesions which are
      relatively frequent in childhood but are little known. Imaging is often used in
      the evaluation of these tumours but their characteristics, particularly on US or
      MRI, have not been studied systematically. OBJECTIVES: To provide an overview of
      the clinical and imaging features of the different disorders, and to correlate
      them with the currently used classification schemes. MATERIAL AND METHODS: Twenty
      five patients with fibrous tumours were evaluated retrospectively. Clinical
      histories were studied for the histopathological diagnosis, age, signs and
      symptoms at presentation, mode of therapy and follow-up where available. Imaging
      findings were analysed for the following variables: number, location, size,
      margin and architecture of soft tissue and/or visceral lesions and the presence
      and pattern of osseous involvement. Comparison with the available literature was
      performed. RESULTS: The following tumour types were encountered: desmoid
      fibromatosis (n = 9), myofibromatosis (n = 7), fibromatosis colli (n = 2),
      congenital-infantile fibrosarcoma (n = 2), adult-type fibrosarcoma (n = 2),
      fibrous hamartoma of infancy (n = 1), angiofibroma (n = 1) and hyaline
      fibromatosis (n = 1). CONCLUSIONS: While some tumours were non-specific in their
      clinical and radiological manifestation, others such as myofibromatosis,
      fibromatosis colli, fibrous hamartoma of infancy and angiofibroma exhibited a
      characteristic pattern which allowed a diagnosis to be made even without
      histology.

PMID- 9662568
TI  - The ultrasound diagnosis of posterior shoulder dislocation associated with Erb's
      palsy.
AB  - A case is presented of an infant with Erb's palsy whose posterior dislocation of
      the humeral head was identified using high-resolution ultrasound following non
      diagnostic plain radiographs. Posterior dislocation is associated with Erb's
      palsy but the diagnosis can be delayed. We suggest the early use of ultrasound in
      patients with Erb's palsy, as this technique is a safe, quick and reliable method
      of excluding posterior dislocation.

PMID- 9662569
TI  - Diffuse neonatal gastrointestinal hemangiomatosis: CT findings.
AB  - A 3-week-old boy presenting with a cutaneous hemangioma and gastrointestinal
      bleeding was found to have gastrointestinal hemangiomatosis involving the entire
      small bowel diagnosed by exploratory laparotomy. We present the striking, diffuse
      enhancement of the small bowel wall in this unusual disorder as demonstrated by
      dynamic contrast-enhanced computed tomography after the bowel was distended with
      non-radiopaque material.

PMID- 9662570
TI  - Mesenchymal hamartoma in a 21-year-old man.

PMID- 9662571
TI  - Colo-colic intussusception associated with pneumatosis cystoides intestinalis.
AB  - This paper describes pneumatosis cystoides intestinalis in association with colo
      colic intussusception in a young teenager. The intussusception was easily reduced
      at barium enema. The recognition of the characteristic filling defects in the
      barium column facilitates a correct diagnosis. This association has only been
      reported previously in six adults.

PMID- 9662572
TI  - Infected duodenal duplication with unusual clinical and radiological
      manifestations: a case report.
AB  - Infected cystic duplication of the duodenum is an unusual lesion. We report a
      case in which pre-operative MR imaging revealed a huge multicystic mass
      masquerading as a cystic lymphangioma or mesenteric cyst. The differential
      diagnosis of this unusual appearance is discussed.

PMID- 9662573
TI  - Percutaneous gastrostomy tube placement in patients with ventriculoperitoneal
      shunts.
AB  - OBJECTIVE: The purpose of this study is to determine the risk of CNS and/or
      peritoneal infection in children with ventriculoperitoneal shunts in whom a
      percutaneous gastrostomy tube is placed. MATERIALS AND METHODS: We placed 205
      gastrostomy or gastrojejunostomy tubes from January of 1991 to December 1996.
      Twenty-three patients (10 boys, 13 girls) had ventriculoperitoneal shunts at the
      time of placement. All shunts were placed at least 1 month prior to placement of
      the gastrostomy tube. The patients ranged in age from 8 months to 16 years with a
      mean age of 6 years, 9 months. Patient weight ranged from 2 kg to 60 kg. All 23
      children required long-term nutritional support due to severe neurologic
      impairment. No prophylactic antibiotics were given prior to the procedure. Of the
      patients, 21/23 had a 14-F Sacks-Vine gastrostomy tube with a fixed terminal
      retention device inserted, using percutaneous fluoroscopic antegrade technique.
      Two of the 23 patients had a Ross 14-F Flexi-flo gastrostomy tube which required
      a retrograde technique due to a small caliber esophagus in these children.
      RESULTS: All 23 children had technically successful placements of percutaneous
      gastrostomy (7) or gastrojejunostomy (16) tubes. Of the children, 21/23 (91%) had
      no complications from the procedure. Two of 23 (9%) patients demonstrated signs
      of peritonitis after placement of their gastrostomy tubes and subsequently had
      shunt infections. In both, children CSF culture grew gram-positive cocci. The
      antegrade technique was used in both children who developed peritonitis.
      CONCLUSION: Our study indicates children with ventriculoperitoneal shunts who
      undergo percutaneous gastrostomy are at greater risk for infection and subsequent
      shunt malfunction. Therefore, we recommend prophylactic antibiotic therapy to
      cover for skin and oral flora.

PMID- 9662574
TI  - Pancreatitis caused by duodenal duplication.
AB  - Two cases of recurrent pancreatitis, due to duodenal duplication, are reported.
      The aim of this paper is to emphasise the role of endoscopic retrograde
      cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography
      (PTC) in the detection of associated pancreaticobiliary anomalies and in the
      planning of the correct surgical approach. The order of imaging in a child with
      recurrent pancreatitis should be US, barium meal and PTC. ERCP is often difficult
      to perform in children.

PMID- 9662575
TI  - Splenogonadal fusion.

PMID- 9662576
TI  - Left mainstem bronchial narrowing: a vascular compression syndrome? Evaluation by
      magnetic resonance imaging.
AB  - BACKGROUND AND OBJECTIVE: Vascular compression of the left mainstem bronchus
      (LMSB) between the descending aorta (DA) and pulmonary artery (PA) has been
      suggested as a cause for LMSB narrowing in children. These anatomic relationships
      have not been compared with those in children with a normal LMSB. Materials and
      methods. We undertook a retrospective review of the medical and radiologic
      records of 10 symptomatic young children (1-19 months, 5 boys, 5 girls) with MR
      demonstration of LMSB narrowing and compared them to 40 young children without
      great vessel or bronchial abnormality on MR (1 week-19 months, 28 boys, 12
      girls). Chest MR evaluation included assessment of airway and great vessel
      anatomy with specific attention to the course of the LMSB and its relationship to
      the adjacent DA and PA. The position of the DA in relation to the spine was
      carefully evaluated. RESULTS: Five children had focal and five had diffuse LMSB
      narrowing. DA position at the level of the crossing LMSB: in 40% of symptomatic
      children the DA was located in front of the adjacent vertebral body; in 40%, 1/2
      3/4 and in 20% 1/4-1/2 of the circumference of the DA was located anterior to the
      spine. In the control group, the DA was prespinal in 10%, with a trend toward a
      more paraspinal location of the DA. The trend toward a difference in position of
      the DA between symptomatic and control patients was statistically significant (P
      < 0.05). DA position was not related to age (up to 19 months). At the level where
      the LMSB crossed the DA, a segment of the PA was located anterior to the LMSB,
      more often the right PA (RPA) or pulmonary bifurcation in symptomatic children
      and the left PA (LPA) in controls. No correlation was apparent between length of
      LMSB narrowing and DA or PA position. Chest radiographic abnormalities, when
      present, were subtle. Excellent MR/bronchoscopic correlation of LMSB narrowing
      was found in nine of the ten symptomatic children. One child underwent posterior
      aortopexy and ligation of the ligamentum arteriosum. CONCLUSION: LMSB narrowing
      is well-defined by MR imaging. While a prespinal position of the DA occurs in
      some children as a normal variant, it is more common and more marked in children
      with LMSB narrowing. Vascular compression of the LMSB between an anteriorly
      positioned DA and the pulmonary artery appears to be important in children with
      symptomatic LMSB narrowing.

PMID- 9662577
TI  - Cervical lung protrusions in children.
AB  - Two main types of cervical lung protrusion are seen in children. The first type,
      which is very uncommon, is a true herniation of the lung apex through a tear or
      defect in Sibson's fascia usually caused by a direct external local trauma. The
      second type, here called for convenience simple lung protrusion, is seen not
      uncommonly in lateral neck roentgenograms, especially in the first years of life,
      and is considered to be a normal finding or an anatomical variant. In the vast
      majority of cases these simple lung protrusions resolve spontaneously in early
      life; cases that fail to resolve may increase in size and become clinically
      significant. This paper reports on 54 children in whom the simple form of
      cervical lung protrusion was observed as an incidental finding in routine lateral
      neck roentgenograms, with a review of previous instances of cervical lung
      protrusions in children described in the literature.

PMID- 9662578
TI  - Intervention for pleural effusions and ascites following liver transplantation.
AB  - BACKGROUND: Small volumes of fluid in the pleural and peritoneal cavities are
      common after paediatric liver transplantation. Occasionally, larger fluid
      collections develop and need intervention by aspiration or insertion of a drain.
      Objective. To assess the incidence of moderate and large pleural and peritoneal
      fluid collections following paediatric liver transplantation, the need for
      intervention and the outcome following radiological and non-radiological
      treatment, with the ultimate objective of recommending a treatment protocol for
      such post-operative fluid collections. MATERIALS AND METHODS: A total of 184
      consecutive liver grafts in 164 children were reviewed. RESULTS: Of 184 grafts,
      31 (16.8%) developed excessive fluid collections requiring intervention (19
      pleural effusions, 8 ascites and 4 effusions and ascites). The effusions were
      first diagnosed between days 1 and 44 after transplant and the ascites between
      days 1 and 14. The initial diagnosis was made radiologically in 21 (91%) of 23
      pleural effusions and in 10 (83%) of 12 ascites. No identifiable cause or
      association was seen in 18 (58%) of 31 cases. The mean duration of the pleural
      effusions and ascites, from onset of treatment to resolution, ranged from 33 +/-
      42 days (SD) to 35 +/- 48 days and from 36 +/- 47 days to 39 +/- 46 days
      respectively. Comparison of the modes of interventional treatment (i.e. unguided,
      radiological and surgical) showed no statistically significant difference in the
      outcome of the management. CONCLUSIONS: Post-transplantation pleural effusions
      and ascites requiring intervention are often without definite cause. They are
      more common with reduced grafts, but this cannot completely explain the
      occurrence or the protracted duration of accumulation in spite of combined
      interventional management. The outcome of treatment is not significantly
      influenced by the mode of intervention except in cases where surgical
      intervention is indicated. Patients could be managed effectively without
      resorting to chronic outpatient aspiration. US contributed significantly in the
      initial and follow-up evaluation of these patients, even in cases of pleural
      effusions, and we would recommend greater use of US in place of radiographs to
      reduce the radiation burden when fluid collections are protracted.

PMID- 9662579
TI  - Unusual sonographic appearance of haemobilia in a child.

PMID- 9662580
TI  - Transitory spinal cord swelling in a 6-year-old boy with Guillain-Barre syndrome.
AB  - A 6-year-old boy developed progressive motor weakness and areflexia. The clinical
      picture, combined with electrophysiological findings, indicated a diagnosis of
      Guillain-Barre syndrome (GBS). MRI on admission revealed spinal cord swelling and
      increased signal intensity within the cord. It is concluded that, since a degree
      of central nervous system involvement can occasionally be part of the spectrum of
      GBS, swelling of the spinal cord without contrast enhancement does not exclude a
      diagnosis of GBS.

PMID- 9662582
TI  - MR findings in pontocerebellar hypoplasia.
AB  - We present four cases with combined hypoplasia of the cerebellum and the ventral
      pons-pontocerebellar hypoplasia (PCH). PCH represents an autosomal recessive
      neurodegenerative disorder with fetal onset. The disease is rare, with less than
      20 cases having been reported. The main findings of PCH and the inclusion
      criteria for our cases can be summarised as progressive microcephaly from birth,
      pontocerebellar hypoplasia documented by MRI and marked chorea, which may change,
      later in childhood, to more dystonic patterns. The cerebral cortex becomes
      progressively atrophic. Motor and mental development are delayed, and epilepsy,
      mainly tonic-clonic seizures, is frequent. The MRI features in all of our cases
      were: (1) Hypoplastic cerebellum situated close to the tentorium. The hypoplastic
      cerebellum has a reduced number of folia, in contrast to the normal number of
      thin folia in simple cerebellar atrophy. (2) The cerebellar hemispheres are
      reduced to bean-like or wing-like structures. The cerebellar hemispheres appear
      to 'float' in the posterior fossa. (3) Markedly hypoplastic ventral pons. (4)
      Slight atrophy of the supratentorial gyral pattern. (5) Dilated cerebromedullary
      cistern and fourth ventricle. (6) Delayed myelination of the white matter. (7) No
      significant disorganisation of brain architecture and no severe corpus callosum
      defect.

PMID- 9662583
TI  - Recurrent deep venous thrombosis complicating PICC line placement in two patients
      with cystic fibrosis and activated protein C-resistance.
AB  - Two patients with cystic fibrosis and activated protein C-resistance experienced
      deep vein thrombosis complicating peripherally inserted central catheter (PICC)
      use. Cystic fibrosis patients may be at increased risk for catheter rotated
      thrombosis.

PMID- 9662584
TI  - Axillary artery aneurysm in tuberous sclerosis: cross-sectional imaging findings.
AB  - A 10-month-old boy with a known diagnosis of tuberous sclerosis presented with
      axillary and brachial masses. Cross-sectional imaging with computed tomography,
      magnetic resonance, and ultrasound demonstrated unsuspected aneurysms of the
      axillary and brachial arteries. The results of these studies significantly
      changed the preoperative planning for this patient, who was scheduled for a
      biopsy of a presumed soft-tissue tumor. To our knowledge, this is the first
      description of the cross-sectional imaging findings in the extremity peripheral
      vascular manifestation of tuberous sclerosis; it has only been previously
      described on angiography in one case. The rare association of peripheral arterial
      aneurysms with tuberous sclerosis is important to recognize not only for clinical
      diagnosis but also for appropriate surgical treatment and genetic counseling.

PMID- 9662585
TI  - Evaluation of a new low-dose digital x-ray device: first dosimetric and clinical
      results in children.
AB  - BACKGROUND: A new low-dose digital X-ray device, based on Charpak's Nobel prize
      winning multiwire chamber, enables the production of images at very low doses.
      Objectives. To present the first dosimetric and clinical results. MATERIALS AND
      METHODS: The analysis was performed on 93 children with scoliosis and 47
      undergoing pelvic radiography. The comparative study between conventional X-ray
      and the new technique focused on three points: (1) the dose delivered by each
      system (2) the diagnostic information provided by each system and (3) comparison
      of image quality criteria with European guidelines. RESULTS: The mean ratio of
      conventional dose to that of the low-dose technique was 13.1 for the spinal
      examination and 18.8 for the pelvis. There was no significant difference in
      diagnostic information available from each modality, but there was a slight
      difference in quality criteria in favour of the conventional technique.
      CONCLUSION: This new device allows spectacular dose reduction, consistent with
      adequate clinical information. Improvements of the prototype will lead to
      extension of potential indications and industrial development.

PMID- 9662587
TI  - The somatostatin receptor-targeted radiotherapeutic [90Y-DOTA-DPhe1,
      Tyr3]octreotide (90Y-SMT 487) eradicates experimental rat pancreatic CA 20948
      tumours.
AB  - Somatostatin receptor-expressing tumours are potential targets for therapy with
      radiolabelled somatostatin analogues. We have synthesized a number of such
      analogues in the past and identified [DOTA-dPhe1, Tyr3]octreotide (SMT 487) as
      the most promising candidate molecule because of its advantageous properties in
      cellular and in vivo tumour models. In the current paper we describe the
      radiotherapeutic effect of yttrium-90 labelled SMT 487 in Lewis rats bearing the
      somatostatin receptor-positive rat pancreatic tumour CA 20948. SMT 487 binds with
      nanomolar affinity to both the human and the rat somatostatin receptor subtype 2
      (sst2) (human sst2 IC50=0.9 nM, rat sst2 IC50=0.5 nM). In vivo, 90Y-SMT 487
      distributed rapidly to the sst2 expressing CA 20948 rat pancreatic tumour, with a
      tumour-to-blood ratio of 49.15 at 24 h post injection. A single intravenous
      administration of 10 mCi/kg 90Y-SMT 487 resulted in a complete remission of the
      tumours in five out of seven CA 20948 tumour-bearing Lewis rats. No regrowth of
      the tumours occurred 8 months post injection. Control animals that were treated
      with 30 microg/kg of unlabelled SMT 487 had to be sacrificed 10 days post
      injection due to excessive growth or necrotic areas on the tumour surface. Upon
      re-inoculation of tumour cells into those rats that had shown complete remission,
      the tumours disappeared after 3-4 weeks of moderate growth without any further
      treatment. The present study shows for the first time the curative potential of
      90Y-SMT 487-based radiotherapy for somatostatin receptor-expressing tumours.
      Clinical phase I studies with yttrium-labelled SMT 487 have started in September
      1997.

PMID- 9662588
TI  - Somatostatin receptor imaging in intracranial tumours.
AB  - The somatostatin analogue [111In-DTPA-d-Phe1]-octreotide (111In-octreotide)
      allows scintigraphic visualization of somatostatin receptor-expressing tissue.
      While it is well known that a large variety of tissues express somatostatin
      receptors and 111In-octreotide scintigraphy has a clearly defined role in various
      neuroendocrine diseases, the clinical value of 111In-octreotide scintigraphy in
      brain tumours is still under clinical investigation. In 124 patients with 141
      brain lesions (63 meningiomas, 24 pituitary adenomas, 10 gliomas WHO class I and
      II, 12 gliomas WHO class III and IV, 11 neurinomas and 2 neurofibromas, 7
      metastases and 12 other varieties: three non-Hodgkin B-cell lymphomas, two
      epidermoids, one abscess, one angioleiomyoma, one chordoma, one
      haemangiopericytoma, one osteosarcoma, one plasmacytoma and one pseudocyst),
      111In-octreotide scintigraphy was performed 4-6 and 24 h after i.v. injection of
      110-220 MBq 111In-octreotide. Planar images of the head in four views with a
      128x128 matrix and single-photon emission tomographic images (64x64 matrix) were
      acquired, and lesions were graded according to qualitative tracer uptake. Fifty
      nine of the 63 meningiomas showed moderate to intense tracer uptake. Nine of 24
      pituitary adenomas were visible; the remaining 15 did not show any tracer uptake.
      None of the class I and II gliomas with an intact blood-brain barrier were
      detected whereas 11/12 class III and IV gliomas showed 111In-octreotide uptake.
      None of the neurinomas or neurofibromas were positive. Five of seven metastases
      were classified as positive, as were the osteosarcoma, two of three non-Hodgkin B
      cell lymphomas, one abscess, one angioleiomyoma, one chordoma and one
      haemangiopericytoma. The other varieties (one non-Hodgkin B-cell lymphoma, two
      epidermoids, one plasmacytoma and one pseudocyst) did not show 111In-octreotide
      uptake. The results demonstrate that a large variety of intracranial lesions
      express somatostatin receptors and therefore can be visualized by [111In-DTPA-d
      Phe1]-octreotide scintigraphy. This technique can be valuable in the
      differentiation between meningiomas and pituitary adenomas, based on qualitative
      tracer uptake. [111In-DTPA-d-Phe1]-octreotide scintigraphy allows differentiation
      between meningiomas and neurinomas or neurofibromas and therefore provides
      complementary information to computed tomography or magnetic resonance imaging.
      Furthermore, this technique allows differentiation between scar tissue and
      recurrent meningiomas postoperatively and can help in non-invasive tumour
      differentiation of multiple intracranial lesions, which can be of value in
      defining the most adequate therapeutic strategy.

PMID- 9662589
TI  - Use of indium-111 pentetreotide somatostatin receptor scintigraphy to detect
      recurrent thyroid carcinoma in patients without detectable iodine uptake.
AB  - We conducted a prospective evaluation of somatostatin receptor scintigraphy (SRS)
      for the diagnosis of recurrent vesicular or papillary thyroid carcinoma in 16
      patients with no detectable iodine uptake. SRS was performed 1, 4 and 24 h after
      intravenous injection of 137-200 MBq of indium-111 pentetreotide. Results were
      interpreted in terms of assumed presence of tumoral tissue: there were three true
      positives (19%), one false-positive (6%) and 12 false-negatives (75%). The three
      true-positive patients had multiple lesions visible on computerized tomography.
      SRS was negative in all patients with a high thyroglobulin level alone. In
      addition, we analyzed the consequences of interpretative criteria and
      somatostatin receptor expression variability for SRS positivity as well as the
      risk of false-positives. We conclude that when iodine uptake cannot be
      demonstrated in patients with suspected recurrence of differentiated thyroid
      carcinoma, SRS would not appear to contribute to diagnosis, and that
      interpretative criteria commonly used for tumours with a high receptor density
      may be too restrictive for tumours with a low receptor density.

PMID- 9662590
TI  - Relative value of thallium-201 and iodine-131 scans in the detection of
      recurrence or distant metastasis of well differentiated thyroid carcinoma.
AB  - Radioactive iodine (131I) has been found to be more sensitive and more specific
      than thallium-201 for the detection of distant metastases and thyroid remnants in
      the neck in cases of well-differentiated thyroid carcinoma. 201Tl has been deemed
      particularly useful in localizing metastases or recurrence in patients with a
      negative 131I scan and abnormal levels of serum thyroglobulin (Tg). This study
      aimed to: (1) determine the value of 201Tl imaging in localizing metastases or
      recurrence in patients with well-differentiated thyroid carcinoma, and (2)
      evaluate the false-positive and false-negative results of 131I and 201Tl
      scintigraphy. Sixty-two thyroid remnant ablated patients who underwent
      simultaneous postoperative 201Tl and 131I scans and and serum Tg determinations
      were evaluated. Fifty patients had papillary thyroid carcinomas and 12 had
      follicular thyroid carcinomas. 201Tl imaging was performed before the 131I
      studies. Of the 62 patients who underwent 201Tl imaging studies, 24 were found to
      have positive results, with local recurrence or distant metastases. Patients with
      positive results in the 201Tl imaging studies tended to be older, were mor often
      male, had higher Tg levels and had a higher recurrence rate. Of these 24
      patients, ten had negative diagnostic or therapeutic 131I scans. Concurrently,
      serum Tg levels were less than 5 ng/ml in five of these ten patients. Three
      patients were deemed false positive by 201Tl scans; one had a parotid tumour, one
      a periodontal abscess and one lung metastasis. Among the 38 patients with
      negative 201Tl scans, 11 had positive findings on 131I scans. Three had distant
      metastases: two with lung metastases and one with bone metastases. Patients with
      false-positive results on 131I scans included those with biliary tract stones,
      ovarian cysts, and breast secretion. Of the 27 patients with negative 201Tl and
      131I scans, 15 had elevated serum Tg levels. Among these, local recurrence
      followed by lung metastases was manifested in a 49-year-old male with papillary
      thyroid carcinoma. In conclusion, both 131I and 201Tl scans are useful in the
      detection of recurrence or distant metastasis of well differentiated thyroid
      cancers. 201Tl scan could in particular be used in patients with a negative 131I
      scan in conjunction with an elevated Tg level.

PMID- 9662591
TI  - Scintigraphic imaging and turnover studies with iodine-131 labelled serum amyloid
      P component in systemic amyloidosis.
AB  - Radiolabelled serum amyloid P component (SAP) is a specific tracer for amyloid.
      Iodine-123 has ideal physical characteristics for scintigraphy but is expensive
      and not widely available. Here we report serial imaging and turnover studies in
      which we labelled SAP with iodine-131, a cheap alternative isotope which would be
      expected to yield poorer images but permit more prolonged turnover measurements.
      Imaging and plasma clearance and whole body retention (WBR) of tracer were
      studied for up to 7 days in ten patients with proven systemic AL amyloidosis and
      two patients in whom the diagnosis was suspected, after i.v. administration of
      about 37 MBq of 131I-SAP. Normal blood pool images were obtained in the latter
      two subjects and amyloidosis was subsequently refuted histologically. WBR at 48 h
      was <60% and 6-h plasma activity was >65% of the injected dose (i.d.). Among the
      other ten patients, amyloid deposits were identified in the spleen in eight
      cases, liver in five and kidneys in four; other sites that gave positive results
      included bone, joints and soft tissues, and the myocardium in one case. Up to 95%
      of the tracer localised into amyloid within 6-h, and the values for WBR became
      progressively more discriminating during the study period, exceeding the normal
      reference value (<25%) in all cases by day 7. The optimal imaging time was found
      to be between 24 and 48 h. The duration of the study enabled us to measure the
      tracer elimination half-life which was increased in all cases by up to tenfold.
      Follow-up studies performed after 2-24 months in four patients who were treated
      with iododoxorubicin showed regression of amyloid in one patient and a small
      increase in one case; in the other two patients the imaging and turnover studies
      were identical to baseline. Despite its unfavourable imaging characteristics,
      131I-SAP produced diagnostic scans in every patient in this series and, coupled
      with the detailed turnover information, is adequate for monitoring disease
      progress.

PMID- 9662592
TI  - Serum amyloid P component scintigraphy in familial amyloid polyneuropathy:
      regression of visceral amyloid following liver transplantation.
AB  - Familial amyloid polyneuropathy (FAP) associated with transthyretin (TTR)
      mutations is the commonest type of hereditary amyloidosis. Plasma TTR is produced
      almost exclusively in the liver and orthotopic liver transplantation is the only
      available treatment, although the clinical outcome varies. Serum amyloid P
      component (SAP) scintigraphy is a method for identifying and quantitatively
      monitoring amyloid deposits in vivo, but it has not previously been used to study
      the outcome of visceral amyloid deposits in FAP following liver transplantation.
      Whole body scintigraphy following injection of iodine-123 labelled SAP was
      performed in 17 patients with FAP associated with TTR Met30 and in five
      asymptomatic gene carriers. Follow-up studies were performed in ten patients,
      eight of whom had undergone orthotopic liver transplantation 1-5 years
      beforehand. There was abnormal uptake of 123I-SAP in all FAP patients, including
      the kidneys in each case, the spleen in five cases and the adrenal glands in
      three cases. Renal amyloid deposits were also present in three of the
      asymptomatic carriers. Follow-up studies 1-5 years after liver transplantation
      showed that there had been substantial regression of the visceral amyloid
      deposits in two patients and modest improvement in three cases. The amyloid
      deposits were unchanged in two patients. In conclusion, 123I-SAP scintigraphy
      identified unsuspected visceral amyloid in each patient with FAP due to TTR
      Met30. The universal presence of renal amyloid probably underlies the high
      frequency of renal failure that occurs in FAP following liver transplantation.
      The variable capacity of patients to mobilise amyloid deposits following liver
      transplantation may contribute to their long-term clinical outcome.

PMID- 9662593
TI  - Different patterns of technetium-99m sestamibi uptake in multiple myeloma.
AB  - Technetium-99m 2-methoxyisobutylisonitrile (99mTc-MIBI) has been proposed as a
      potential tracer in patients with multiple myeloma (MM). The aims of this study
      were to evaluate the incidence of various patterns of diffuse 99mTc-MIBI uptake
      in patients with MM, to assess their relationship with clinical status and stage
      of disease, and to try to clarify the meaning of the diffuse bone marrow uptake
      of 99mTc-MIBI. Thirty-nine consecutive patients with MM were studied. Twenty-nine
      of these patients had active disease (13 in stage I, ten in stage II, and six in
      stage III) and ten were in remission after chemotherapy. Anterior and posterior
      whole-body scans were obtained 10 min after i.v. injection of 555 MBq of 99mTc
      MIBI. The scans were classified as showing: pattern N, when only physiological
      uptake was present; pattern D, when diffuse bone marrow uptake was observed;
      pattern F, when areas of focal uptake of the radiotracer were evident; or pattern
      D+F, when both D and F patterns were observed. Diffuse bone marrow uptake was
      scored according to extension and intensity. Seven of the 39 patients (18%)
      showed pattern N, 18 (46%) pattern D, 2 (5%) pattern F, and 12 (31%) pattern D+F.
      Of the 32 patients with a positive 99mTc-MIBI scan (i.e. showing pattern D, F or
      D+F), 29 (91%) had active disease. Only three patients in remission showed
      pattern D, but with a very low bone marrow uptake score. Both extension and
      intensity of diffuse bone marrow uptake correlated with the amount of the
      monoclonal component and the percentage of bone marrow plasma cells. The
      distribution of the 99mTc-MIBI uptake patterns differed among patients in
      different stages of disease. Using as criteria for advanced stage the presence of
      either focal uptake (pattern F or D+F) or pattern D with a high score, high (90%)
      diagnostic accuracy was obtained. In conclusion, the patterns of 99mTc-MIBI
      uptake in patients with MM are related to both the clinical status and the stage
      of disease. The presence of focal uptake or of intense diffuse bone marrow uptake
      suggests that the patient has active and advanced stage disease, while a negative
      scan in a patient with MM clearly indicates remission.

PMID- 9662594
TI  - Whole-body positron emission tomography using fluorodeoxyglucose for staging of
      lymphoma: effectiveness and comparison with computed tomography.
AB  - The purpose of this study was to evaluate whole-body positron emission tomography
      (WB-PET) as a staging modality in Hodgkin's disease (HD) and non-Hodgkin lymphoma
      (NHL) and to compare it with computed tomography (CT) in a retrospective study.
      Seventy-one WB-PET studies using fluorodeoxyglucose (FDG) and 49 CT examinations
      were performed in 19 women and 31 men. Transaxial images were acquired and
      reformatted coronally and sagittally in PET. CT sections were obtained from the
      skull base to the pelvic floor. The written reports of the imaging data were
      compared with a reference standard constructed on the basis of all the data on
      the individual patients, including clinical follow-up of at least 6 months. The
      sensitivity and specificity of PET were, respectively, 86% and 96% for HD (n=53),
      and 89% and 100% for NHL (n=18). For CT sensitivity and specificity were 81% and
      41% for HD (n=33) and 86% and 67% for NHL (n=16). Differences between PET and CT
      sensitivities were not significant, while in HD there was a significant
      difference in the specificity of PET and CT examinations, mainly because CT was
      unable to distinguish between active or recurrent disease and residual scar
      tissue after therapy. FDG tumour uptake was found in high- as well as low-grade
      NHL patients. In conclusion, PET appears to be highly sensitive and specific for
      staging of lymphoma. It is at least as sensitive as CT, and more specific,
      particularly in patients undergoing restaging, where a well-recognized diagnostic
      dilemma in CT is the presence of a post-therapeutic residual mass.

PMID- 9662595
TI  - Use of carbon-11 methionine positron emission tomography to assess malignancy
      grade and predict survival in patients with lymphomas.
AB  - The aim of this study was to investigate whether uptake of carbon-11 methionine
      (MET) is associated with histological grade of malignancy and survival in
      patients with newly diagnosed or recurrent lymphoma. Thirty-two patients with
      histologically confirmed lymphoma participated in the study. Twenty-six (81%)
      were studied before any therapy and six before treatment for recurrent disease.
      Twenty-eight patients had non-Hodgkin's lymphoma and four had Hodgkin's disease.
      An ECAT 931/08-12 positron emission tomography (PET) scanner was used for PET
      imaging. After the transmission scan, a median dose of 293 MBq of MET was
      injected intravenously and dynamic images were acquired for 40 min. The uptake of
      MET in tumour was measured as the standardized uptake value (SUV) and influx
      constant (Ki). The SUV formula was also adjusted to the predicted value of lean
      body mass (SUVlean) and body surface area (SUVBSA). The PET results were
      correlated with the clinical follow-up data. The median SUV in 32 malignant
      lesions was 6.6 (range, 1.9-12.4) and the median Ki was 0. 116 min-1 (range,
      0.025-0.201, n=23). The median SUV was 7.0 (range, 5.4-12.4, n=9) in high, 6.2
      (range, 1.9-10.4, n=11) in intermediate and 5.7 (range, 3.8-8.3, n=8) in low
      grade lymphomas. One intermediate grade lymphoma of the skin was visually
      negative (SUV 1. 9). In Hodgkin's disease the median SUV was 7.0 (range, 3.2-7.9,
      n=4). The median Ki value was 0.162 min-1 (range, 0.147-0.197, n=7) in high,
      0.099 (range, 0.025-0.152, n=10) in intermediate, and 0.078 (range, 0.056-0.152,
      n=4) in low grade lymphomas and 0.149 (range, 0. 096-0.201, n=2) in Hodgkin's
      disease. The difference between high and other grade non-Hodgkin's lymphomas was
      significant when using Ki (P<0.001), but not with SUV, SUVlean or SUVBSA. The
      final outcome of the patients was not related to MET uptake. Lymphomas with a
      high Ki value tended to have a high S-phase fraction (r2=0.46, P=0.043). It is
      concluded that MET PET is highly sensitive for the detection of untreated and
      recurrent lymphomas. Differentation of high grade lymphomas from lower malignancy
      grades seems to be possible if graphical analysis is applied to calculate Ki for
      MET. However, prediction of survival is not possible with MET PET.

PMID- 9662596
TI  - Role of positron emission tomography using fluorine-18 fluoro-2-deoxyglucose in
      predicting improvement in left ventricular function in patients with idiopathic
      dilated cardiomyopathy.
AB  - Improvement in left ventricular (LV) function in patients with idiopathic dilated
      cardiomyopathy (DCM) by medical treatment has been suggested. Thus, it is
      important to evaluate which patients will respond to medical therapy. Positron
      emission tomography (PET) with fluorine-18 fluoro-2-deoxyglucose (FDG) and
      cardiac catheterization were performed in 20 patients with DCM before the
      initiation of medical therapy. The regional myocardial glucose utilization rate
      (rMGU) was measured with FDG PET. Subjects were divided into two groups, group 1
      (event-free patients, n=10) and group 2 (clinical cardiac events, n=10).
      Haemodynamic and PET parameters before the initiation of medication were compared
      between the two groups and between patients with and patients without improvement
      in LV function. Ejection fraction (EF) was significantly higher in group 1
      (35.8%+/-9.0%) than in group 2 (24.8%+/-7.0%) and LV end-diastolic pressure
      (LVEDP) was significantly lower in group 1 (8.4+/-1.7 mmHg) than in group 2
      (11.6+/-3.5 mmHg). Average rMGU (mg min-1 100 g-1) was similar in group 1 (11.2+/
      2.5 mg min-1 100 g-1) and group 2 (11.2+/-2.9 mg min-1 100 g-1), while %CV of
      rMGU was significantly lower in group 1 (11.1%+/-6.3%) than in group 2 (29. 9%+/
      13.9%, P<0.01). Furthermore, LV function normalized in seven patients in group 1.
      In these seven patients, EF (35.1%+/-10.9%), LVEDP (8.2+/-2.0 mmHg) and average
      rMGU (11.8+/-2.7 mg min-1 100 g-1) were comparable with those in patients without
      LV functional improvement (EF: 31.6%+/-9.1%; LVEDP: 10.7+/-3.3 mmHg; average
      rMGU: 10.8+/- 2.7 mg min-1 100 g-1). However,% CV of rMGU in patients with LV
      functional improvement (9.6%+/-5.6%) was significantly lower than in those
      without such improvement (26.3%+/-14.1%, P<0.01). %CV of rMGU <13.6% predicted
      prognosis with a sensitivity of 80%, a specificity of 100% and an accuracy of
      90%. %CV of rMGU <13.6% also predicted improvement in LV function, with a
      sensitivity of 75%, a specificity of 92% and an accuracy of 85%. However, EF
      failed to predict improvement of LV function. In is concluded that homogeneous
      myocardial glucose utilization rate can predict both prognosis and improvement in
      LV function achieved by medical therapy in patients with DCM.

PMID- 9662597
TI  - Combined evaluation of rest-redistribution thallium-201 tomography and low-dose
      dobutamine echocardiography enhances the identification of viable myocardium in
      patients with chronic coronary artery disease.
AB  - The purpose of this study was to evaluate whether combined evaluation by
      discriminant analysis of rest-redistribution thallium-201 tomography and low-dose
      dobutamine echocardiography enhances the accuracy in identifying viable
      myocardium in patients with chronic coronary artery disease. Rest-redistribution
      201Tl has high sensitivity but low specificity in identifying viable myocardium,
      while the opposite is true for low-dose dobutamine echocardiography. Forty-six
      patients underwent low-dose dobutamine echocardiography and rest-redistribution
      201Tl tomography on the same day. Rest echocardiography was repeated at least 30
      days (mean 40+/-20) after myocardial revascularization. Discriminant analysis was
      applied to the results of 201Tl tomography and dobutamine echocardiography to
      classify a/dyskinetic segments as viable or non-viable. In 92 a/dyskinetic
      segments that were revascularized, rest-redistribution 201Tl tomography yielded
      an accuracy of 75%, while the accuracy of dobutamine echocardiography was 70%
      (P<0.05). When discriminant analysis was used, the combined evaluation gave an
      accuracy of 83% (P<0.05 vs both tests). These findings demonstrate that low-dose
      dobutamine echocardiography and 201Tl imaging are useful and complementary
      techniques for identifying viable myocardium in patients with chronic coronary
      artery disease. Combined evaluation by discriminant analysis significantly
      improves accuracy, although the cost-effectiveness of such an approach remains to
      be determined.

PMID- 9662598
TI  - Measurement of myocardial blood flow with oxygen-15 labelled water: comparison of
      different administration protocols.
AB  - Positron emission tomography (PET) in conjunction with C15O2 or H215O can be used
      to measure myocardial blood flow (MBF) and tissue fraction (TF), i.e. the
      fraction of the tissue mass in the volume of the region of interest. However,
      with C15O2 inhalation, the tissue fraction in the septum is overestimated. Bolus
      injection of H215O together with arterial cannulation gives very precise results
      but is invasive. The purpose of this study was to develop a method which
      circumvents these problems. A four-parameter model with parameters for MBF, TF
      and spill-over fractions from both left and right ventricular cavities was
      developed. This method was compared with a three-parameter model (no right
      ventricular cavity spill-over) in both septal and non-septal regions of interest
      for three different administration protocols: bolus injection of H215O, infusion
      of H215O and inhalation of C15O2. It was found that MBF can be measured with
      intravenous administration of H215O without the requirement for arterial
      cannulation. The four-parameter protocol with bolus injection was stable in
      clinical studies. The four-parameter model proved essential for the septum, where
      it gave highly significantly better fits than did the three-parameter model
      (P<0.00003 in each of 15 subjects). Administration of H215O together with this
      four-parameter model also circumvented the problem of overestimation of TF in the
      septum seen with C15O2 inhalation. In addition, the radiation dose of H215O
      protocols is lower than that of C15O2 inhalation. Using a left atrial input curve
      instead of a left ventricular cavity input curve gave the same mean MBF and TF.

PMID- 9662599
TI  - Technetium-99m mercaptoacetyltriglycine clearance values in children with minimal
      renal disease: can a normal range be determined?
AB  - Use of technetium-99m labelled mercaptoacetyltriglycine (99mTc-MAG3) simplifies
      and improves the quantification of renal clearance in children by virtue of its
      permanent availability, good imaging properties and low radiation exposure. Due
      to the lack of reference values for 99mTc-MAG3 clearance in children, the
      Paediatric Task Group of the EANM initiated a multicentre study to evaluate 99mTc
      MAG3 clearance values in children with minimal renal disease. One hundred and
      twenty-five children aged between 12 months and 17 years, classified as renally
      healthy using defined diagnostic criteria, were included in the study. 99mTc-MAG3
      clearance was calculated using an algorithm on the basis of a single blood sample
      taken at any time between 30 and 40 min after tracer injection. In addition, the
      absolute 99m-Tc-MAG3 clearance values were normalized to body surface area. For
      further evaluation the children were classified into several groups according to
      age. There was a continuous increase in non-corrected 99mTc-MAG3 clearance values
      from the age of 1 year up to the age of 17 years (mean value <2 years: 98+/-57
      ml/min; mean value >8 years: 208+/-66 ml/min). Normal clearance values for adults
      were achieved by the age of 8 years. Analysis of the relationship between non
      corrected clearance and age yielded a correlation coefficient of r=0.7. When
      these absolute clearance values were normalized to body surface area, we found
      nearly constant clearance values for all age groups, with a mean clearance value
      of 315+/-114 ml/minx1.73 m2. The correlation coefficient for the relationship
      between normalized clearance and age was r=0.28. In conclusion, the clearance of
      99mTc-MAG3 increases continuously throughout childhood into adolescence due to
      the maturation and growth of the kidney. After normalization of the absolute
      clearance to body surface area, no correlation between clearance and age could be
      proven.

PMID- 9662600
TI  - Bidirectional transport of iminodiacetic organic anion analogues between plasma
      and hepatocyte.
AB  - The kinetics of organic anions are well described and back-diffusion from
      hepatocyte to plasma is accepted. Although iminodiacetic (IDA) analogues, as
      organic anions, should also show bidirectional transport between hepatocyte and
      plasma, this has not been directly demonstrated heretofore. The aim of this study
      was to directly demonstrate back-diffusion and to quantify it in terms of its
      fractional rate constant. Kinetics of diethyl IDA were studied in three
      anaesthetised dogs in which femoral arterial and hepatic venous samples were
      obtained after injection of tracer into (a) a peripheral vein or (b) hepatic
      artery or portal vein. Arterial time-concentration curves were also compared
      between peripheral venous and either hepatic arterial or portal venous
      injections. Time-activity curves were recorded from regions of interest over the
      cardiac blood pool and peripheral hepatic parenchyma in 30 patients undergoing
      routine IDA hepatobiliary imaging with diethyl IDA or mebrofenin and fractional
      rate constants of clearance of IDA from the hepatocyte compared between
      compartmental and deconvolution analyses. After peripheral injection in dogs,
      there was an early arteriovenous concentration gradient across the liver
      indicating an hepatocyte extraction fraction in the three animals of 0.9, 0.8 and
      0.6. The net extraction fraction decreased exponentially over 40 min. Time
      concentration curves from hepatic vein and femoral artery were virtually
      superimposed following intrahepatic injections. Peripheral arterial curves,
      however, had different shapes according to whether injections were intrahepatic
      or peripheral, and were consistent with significant back-diffusion. In clinical
      studies, the blood disappearance curves were fitted as the sum of two
      exponentials and the liver curves as the difference of two exponentials (with
      rate constants denoted alpha1h and alpha2h). Based on compartmental analysis of
      the blood curves, the sum of the fractional rate constants of tracer movement
      from hepatocyte to bile canaliculus (k32) and to plasma (k12) was similar to and
      correlated with the rate constant, alpha, of the hepatocyte impulse response
      function (r=0.62, n=30, P<0.001). In contrast, alpha1h and alpha2h were
      respectively clearly greater and smaller than alpha. Moreover, neither of these
      hepatic rate constants correlated with alpha. Diffusion of IDA from hepatocyte to
      blood is significant and even in the presence of normal liver function accounts
      for about 50% of IDA transport out of the hepatocyte. It should be taken into
      account in pharmacokinetic studies based on either compartmental or deconvolution
      analysis.

PMID- 9662601
TI  - Transmission scanning in emission tomography.
AB  - Attenuation correction in single-photon (SPET) and positron emission (PET)
      tomography is now accepted as a vital component for the production of artefact
      free, quantitative data. The most accurate attenuation correction methods are
      based on measured transmission scans acquired before, during, or after the
      emission scan. Alternative methods use segmented images, assumed attenuation
      coefficients or consistency criteria to compensate for photon attenuation in
      reconstructed images. This review examines the methods of acquiring transmission
      scans in both SPET and PET and the manner in which these data are used. While
      attenuation correction gives an exact correction in PET, as opposed to an
      approximate one in SPET, the magnitude of the correction factors required in PET
      is far greater than in SPET. Transmission scans also have a number of other
      potential applications in emission tomography apart from attenuation correction,
      such as scatter correction, inter-study spatial co-registration and alignment,
      and motion detection and correction. The ability to acquire high-quality
      transmission data in a practical clinical protocol is now an essential part of
      the practice of nuclear medicine.

PMID- 9662602
TI  - Design of hypoxia-targeting radiopharmaceuticals: selective uptake of copper-64
      complexes in hypoxic cells in vitro.
AB  - The well-known perfusion tracer CuPTSM, labelled with 62Cu or 64Cu, is believed
      to be trapped in cells non-selectively by a bioreductive mechanism. It is
      proposed that by modifying the ligand to increase its electron donor strength
      (for example by adding alkyl functionality or replacing sulphur ligands with
      oxygen ligands), the copper complexes will become less easily reduced and tracers
      with selectivity for hypoxic tissues could thus be developed. The aim of this
      work was to prepare 64Cu-labelled complexes of two series of ligands, based on
      the bis(thiosemicarbazone) (13 ligands) and bis(salicylaldimine) (3 ligands)
      skeletons, and to evaluate the hypoxia dependence of their uptake in cells. The
      complexes were incubated with Chinese hamster ovary cells under normoxic and
      hypoxic conditions, and the cells isolated by centrifugation to determine
      radioactivity uptake at various time points up to 90 min. Several members of both
      series demonstrated significant (P<0.05) or highly significant (P<0.01) hypoxia
      selectivity, indicating that both series of complexes offer a basis for
      development of hypoxia-targeting radiopharmaceuticals for positron emission
      tomography (60Cu, 61Cu, 62Cu, 64Cu) and targeted radiotherapy (64Cu, 67Cu).

PMID- 9662603
TI  - Stability versus reactivity of "3+1" mixed-ligand technetium-99m complexes in
      vitro and in vivo.
AB  - "3+1" technetium-99m mixed-ligand complexes as relevant to the development of a
      third generation of 99mTc radiopharmaceuticals were investigated in vivo and in
      vitro in the blood of rats. Surprisingly, in whole blood the complexes, which
      proved to be stable in saline, PBS of pH 7.4 and in plasma, were converted into
      two radioactive, more hydrophilic metabolites. Small structural differences in
      the complex molecule have a profound influence on the rate of metabolism of the
      complexes. To obtain an understanding of this unexpected reactivity,
      transchelation reactions with glutathione (GSH) were hypothesized and this
      hypothesis substantiated by challenge experiments carried out with a series of
      99mTc and analogous rhenium complexes and GSH. In vitro studies in human plasma,
      whole blood and erythrocytes also revealed conversion of the complexes, though,
      at a much slower rate. Structural parameters influencing the stability of the
      complexes and consequences for the radiopharmaceutical design are discussed.

PMID- 9662604
TI  - A consensus protocol for white blood cells labelling with technetium-99m
      hexamethylpropylene amine oxime. International Society of Radiolabeled Blood
      Elements (ISORBE)

PMID- 9662605
TI  - The importance of endothelium and interstitial fluid in nuclear medicine.

PMID- 9662606
TI  - Nucleotide sequence and chromosomal location of L-lactate dehydrogenase gene from
      Streptococcus pneumoniae.
AB  - We report here the 1244-bp sequence of a Streptococcus pneumoniae chromosomal
      fragment that contains the putative promoter and protein-coding region of the
      lactate dehydrogenase gene (ldh). The nucleotide sequence predicts a protein of
      327 aa with a molecular weight of 35,202 daltons, after removal of the N-terminal
      methionine residue. The ldh gene is located on the ApaI fragment 1 and SmaI
      fragment 2 of the previously reported physical map of S. pneumoniae chromosome.

PMID- 9662607
TI  - Genetic diversity of Bacillus cereus/B. thuringiensis isolates from natural
      sources.
AB  - The genetic diversity and relationships among 154 Bacillus cereus/B.
      thuringiensis isolates recovered from soil samples from five geographic areas in
      Norway were investigated with multilocus enzyme electrophoresis (MEE). Cluster
      analysis revealed two major groups (designated cluster I and cluster II)
      separated at genetic distance greater than 0.55. Cluster I included 62
      electrophoretic types (ETs) originating from all five locations, whereas, in
      cluster II, all but one isolate were from the same location. The isolates were
      also serotyped with B. thuringiensis flagellar antisera, and 28 distinct
      serotypes were identified. In general, serotyping did not show correlation to the
      genetic diversity of the isolates. The presence of IS231- and IS240-like
      transposable elements was detected in 14% of the strains of cluster II only.
      Parasporal crystals were observed in three strains; ten other strains were toxic
      to Trichoplusia ni. We conclude that B. cereus/B. thuringiensis from soil exhibit
      a high degree of recombination.

PMID- 9662608
TI  - Tindallia magadii gen. nov., sp. nov.: an alkaliphilic anaerobic ammonifier from
      soda lake deposits.
AB  - Strain Z-7934, an alkaliphilic, obligately anaerobic, fermentative, asporogenous
      bacterium with Gram-positive cell wall structure, was isolated from soda deposits
      in Lake Magadi, Kenya. The organism ferments only a few amino acids,
      preferentially arginine and ornithine, with production of acetate, propionate,
      and ammonia. It is a true alkaliphile, with pH range for growth ranging from 7.5
      to 10.5 (optimum pH 8.5), and growth is dependent on the presence of sodium ions.
      The G+C content of the genomic DNA is 37.6 mol%. 16S rDNA sequence analysis of
      strain Z-7934 shows that it belongs phylogenetically to cluster XI of the low G+C
      Gram-positive bacteria. On the basis of its distinct phylogenetic position and
      unique physiological properties, we propose a new genus and new species,
      Tindallia magadii, for this strain. The type strain is Z-7934(T) (=DSM 10318).

PMID- 9662609
TI  - Detection of microbial pathogens in shellfish with multiplex PCR.
AB  - Multiplex PCR amplification of uidA, cth, invA, ctx, and tl genes was developed
      enabling simultaneous detection in shellfish of Escherichia coli, an indicator of
      fecal contamination and microbial pathogens, Salmonella typhimurium, Vibrio
      vulnificus, V. cholerae, and V. parahaemolyticus, respectively. Each of the five
      pairs of oligonucleotide primers was found to support PCR amplifications of only
      its targeted gene. The optimized multiplex PCR reaction utilized a PCR reaction
      buffer containing 2.5 mM MgCl2 and primer annealing temperature of 55 degrees C.
      Oyster tissue homogenate seeded with these microbial pathogens was subjected to
      DNA purification by the Chelextrade mark 100 (BioRad) method. The sensitivity of
      detection for each of the microbial pathogens was </=10(1)-10(2) cells following
      a "double" multiplex PCR amplification approach. Amplified target genes in a
      multiplex PCR reaction were subjected to a colorimetric GeneCombtrade mark
      (BioRad) DNA-DNA hybridization assay. This assay was rapid and showed sensitivity
      of detection comparable to the agarose gel electrophoresis method. The
      colorimetric GeneCombtrade mark assay avoids use of hazardous materials inherent
      in conventional gel electrophoresis and radioactive-based hybridization methods.
      Multiplex PCR amplification, followed by colorimetric GeneCombtrade mark DNA-DNA
      hybridization, has been shown to be an effective, sensitive, and rapid method to
      detect microbial pathogens in shellfish.

PMID- 9662610
TI  - A DNA fragment from the cyanobacterium Synechocystis sp. PCC 6803 mediates gene
      expression inducible by osmotic stress in E. coli.
AB  - Fragments of Synechocystis-DNA driving salt-induced gene expression in E. coli
      were isolated with translational fusions to a 'lacZ gene. One fragment (fragment
      19) showed a NaCl-dependent activation of betaGal expression with the maximum of
      a ninefold increase in enzyme activity. A similar induction was triggered by the
      nonionic osmolyte sucrose, indicating an osmotically dependent activation. On the
      contrary, transcriptional activity of the DNA fragment 19 was only slightly
      enhanced under salt stress conditions, suggesting a posttranscriptional mechanism
      of induction. Primer extension assay was performed to identify the transcription
      initiation site. Upstream regions share weak homology to the "-10" hexamer
      consensus of E. coli sigma70 promoters. The most thermodynamically stable
      secondary structure for the nontranslated part of the mRNA indicated that
      potential translation initiation sites might be blocked, leading to a low basal
      translation, whereas osmotic stress-induced changes of mRNA structure could be
      involved to increase translation. In order to analyze the function of fragment 19
      in Synechocystis, promoter-probe plasmids were constructed allowing the stable
      integration of transcriptional and translational reporter gene fusions into the
      cyanobacterial chromosome. Quantitative assessment of reporter gene expression
      revealed a weak constitutive promoter activity of fragment 19 in Synechocystis.
      Sequence analysis showed that fragment 19 comprises 223 bp of the ORF sll0747 of
      the Synechocystis genome.

PMID- 9662611
TI  - Effect of N-linked glycosylation on secretion, activity, and stability of alpha
      amylase from Aspergillus oryzae.
AB  - The effect of N-linked glycosylation on secretion, activity, and stability of
      alpha-amylase from Aspergillus oryzae grown as dispersed filaments was studied.
      In the presence of tunicamycin the fungus grew either as dispersed filaments or
      as one large pellet, whereas growth was as dispersed filaments in all control
      cultures. The presence of tunicamycin affected neither biomass, level of secreted
      alpha-amylase, nor total amount of secreted protein in cultures growing as
      dispersed filaments. In these cultures both glycosylated and nonglycosylated
      alpha-amylase appeared in the culture medium as well as in the cells, whereas in
      control cultures only the glycosylated form of alpha-amylase was found in the
      medium and in the cells. The presence of nonglycosylated alpha-amylase in the
      medium seemed to result from active secretion rather than from autolysis of the
      mycelium or extracellular deglycosylation. Deglycosylation with Endo H of crude
      alpha-amylase in culture filtrate did not affect its stability towards heat, acid
      pH, or proteolytic degradation.

PMID- 9662612
TI  - Genetic transformation in Haemophilus parainfluenzae clinical isolates.
AB  - Haemophilus parainfluenzae isolates recovered from patients with respiratory
      diseases were studied for their ability to undergo genetic transformation by
      isogenic DNA. Two chromosomal markers, streptomycin resistance and nalidixic acid
      resistance, were tested for transformation efficiencies in H. parainfluenzae
      recipients from three biotypes. Most efficient in transformation was biotype II,
      followed by biotype I, while biotype III was nontransformable. Lack of
      transformation was not owing to poor donor activity of DNA, but to inability of
      the cells to develop competence. Strains that formed clumps in liquid media were
      nontransformable. Since the transformable biotype II is one of the prevalent
      biotypes world wide, one can speculate that DNA transformation probably plays a
      major role in the spread of drug resistance in H. parainfluenzae.

PMID- 9662613
TI  - Metabolism of explosive compounds by sulfate-reducing bacteria.
AB  - The metabolism of various explosive compounds-1,3,5-trinitrobenzene (TNB),
      hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), and octahydro-1,3,5,7-tetranitro
      1,3,5,7-tetraazocine (HMX)-by a sulfate-reducing bacterial consortium,
      Desulfovibrio spp., was studied. The results indicated that the Desulfovibrio
      spp. used all of the explosive compounds studied as their sole source of nitrogen
      for growth. The concentrations of TNB, RDX, and HMX in the culture media dropped
      to below the detection limit (<0.5 ppm) within 18 days of incubation. We also
      observed the production of ammonia from the nitro groups of the explosive
      compounds in the culture media. This ammonia served as a nitrogen source for the
      bacterial growth, and the concentration of ammonia later dropped to <0.5 mg/L.
      The sulfate-reducing bacteria may be useful in the anaerobic treatment of
      explosives-contaminated soil.

PMID- 9662614
TI  - Pasteurella haemolytica ultraviolet-irradiated vaccine by parenteral and aerosol
      routes compared in the goat model.
AB  - Positive control 1 (PC1) (n = 9) goats were injected transthoracically into the
      left lung with live Pasteurella haemolytica biovar A, serovar 1 (PhA1) in
      polyacrylate (PA) beads on days 0 and 21. Positive control 2 (PC2) (n = 6) goats
      were nebulized with live PhA1 and PA beads on days 0 and 21. Negative control
      (NC) goats (n = 6) were each injected transthoracically into the left lung with
      PA beads alone on days 0 and 21. Four groups (n = 6) were administered PA beads
      mixed with ultraviolet (UV) killed PhA1 on days 0 and 21. The treatment doses of
      bacteria for these groups were principal group 1 (PR1) injected into the left
      lung (7.7 x 10(10) cfu); PR2, 7.7 x 10(10) UV-killed PhA1 injected subcutaneously
      (SC); PR3, 7.7 x 10(10) UV-killed PhA1 injected SC only on day 21; PR4, nebulized
      with PA beads mixed with 5.6 x 10(10) cfu of UV-killed PhA1; and PR5, nebulized
      with PA beads mixed with 5 x 10(8) cfu of UV-killed PhA1. All goats were
      challenged transthoracically in the right lung with 1 x 10(8) cfu of live PhA1 on
      day 42 and necropsied on day 46. The sizes of consolidated lung lesions at the
      challenge site were used as a measure of immunity. The data show that the
      introduction of live PhA1 into the lungs of goats, either by injection or
      aerosolization, offers excellent protection against a subsequent homologous
      challenge. The data also demonstrate that two transthoracic injections (21 days
      apart) of UV-killed PhA1 (PR1), and subcutaneous injection of UV-killed PhA1(PR2)
      also offer excellent protection against a subsequent homologous live PhA1
      challenge. One SC injection of UV-killed PhA1 (PR3) appears to offer only partial
      protection against a subsequent homologous live PhA1 challenge. Inhalation of UV
      killed PhA1 mixed with PA beads (PR4 and PR5) induced no protection in goats
      against a subsequent live PhA1 transthoracic challenge.

PMID- 9662615
TI  - Indole acetic acid and its metabolism in root nodules of a monocotyledonous tree
      Roystonea regia.
AB  - A monocotyledonous tree, Roystonea regia, was found to bear root nodules. The
      root nodules contained a high amount (16.9 microg/g fresh mass) of indole acetic
      acid (IAA). A big tryptophan pool (1555.1 microg/g fresh mass) was found in the
      root nodules, which might serve as a source of IAA production. The presence of
      IAA-metabolizing enzymes IAA oxidase and peroxidase indicated metabolism of IAA
      in the root nodules. The symbiont isolated from the root nodules of R. regia, a
      Rhizobium sp., produced high amount of IAA in culture when supplemented with
      tryptophan. The possible role of this IAA production in the monocotyledonous tree
      Rhizobium symbiosis is discussed.

PMID- 9662616
TI  - Cytosolic neutral proteinases of Paracoccidioides brasiliensis.
AB  - Cytosolic proteinases were assayed in both morphological phases of
      Paracoccidioides brasiliensis. Preparations from the mycelial phase were more
      active in vitro than those from the yeast cells. Optimal proteinase activities
      for both phases occurred at pH's between 6.0 and 9.0, and at 45 degrees C.
      Gelatin-SDS-PAGE electrophoresis separated several bands (58-112 kDa) in mycelial
      preparations; a single band (70 kDa) was seen in yeast preparations. Enzymatic
      activities were inhibited by antipain, phenyl methyl sulfonyl fluoride (PMSF),
      and chymostatin, suggestive of serine proteinases. Partial inhibition of the
      mycelial enzymes by ethylene diamine tetraacetic acid (EDTA), 1,10
      phenanthroline, and iodoacetamide, also suggested the presence of cysteine- and
      metallo-proteinases. The enzymatic activity increased in preparations extracted
      from yeast cells transforming to mycelia, and decreased in preparations obtained
      from the reverse process.

PMID- 9662617
TI  - The effect of galE gene inactivation on lipopolysaccharide profile of
      Helicobacter pylori.
AB  - The galE gene product, UDP-galactose 4-epimerase, mediates the incorporation of
      galactose in extracellular polysaccharide materials such as the O-side chain of
      lipopolysaccharide (LPS). The O-side chain in H. pylori LPS has been shown to
      cross-react with Lewis x and/or y blood group antigens, suggesting its potential
      involvement in H. pylori-linked autoimmune disease. To study its role in H.
      pylori LPS biosynthesis, the galE gene was cloned, sequenced, and a galE-knockout
      H. pylori strain was constructed. The H. pylori galE gene encoded a protein of
      344 amino acids with a molecular weight of 39K. The LPS profile from the galE
      knockout H. pylori strain showed a lower molecular weight than that of the
      parental strain, indicating the involvement of the galE gene in LPS biosynthesis
      of H. pylori.

PMID- 9662618
TI  - Encyclopedia of the mouse genome VII. Mouse chromosome 1.

PMID- 9662619
TI  - Encyclopedia of the mouse genome VII. Mouse chromosome 2.

PMID- 9662620
TI  - Encyclopedia of the mouse genome VII. Mouse chromosome 3.

PMID- 9662621
TI  - Encyclopedia of the mouse genome VII. Mouse chromosome 4.

PMID- 9662622
TI  - Encyclopedia of the mouse genome VII. Mouse chromosome 5.

PMID- 9662623
TI  - Encyclopedia of the mouse genome VII. Mouse chromosome 6.

PMID- 9662624
TI  - Encyclopedia of the mouse genome VII. Mouse chromosome 7.

PMID- 9662625
TI  - Encyclopedia of the mouse genome VII. Mouse chromosome 8.

PMID- 9662626
TI  - Encyclopedia of the mouse genome VII. Mouse chromosome 9.

PMID- 9662628
TI  - Encyclopedia of the mouse genome VII. Mouse chromosome 11.

PMID- 9662627
TI  - Encyclopedia of the mouse genome VII. Mouse chromosome 10.

PMID- 9662629
TI  - Encyclopedia of the mouse genome VII. Mouse chromosome 12.

PMID- 9662630
TI  - Encyclopedia of the mouse genome VII. Mouse chromosome 13.

PMID- 9662631
TI  - Encyclopedia of the mouse genome VII. Mouse chromosome 14.

PMID- 9662632
TI  - Encyclopedia of the mouse genome VII. Mouse chromosome 15.

PMID- 9662633
TI  - Encyclopedia of the mouse genome VII. Mouse chromosome 16.

PMID- 9662634
TI  - Encyclopedia of the mouse genome VII. Mouse chromosome 17.

PMID- 9662635
TI  - Encyclopedia of the mouse genome VII. Mouse chromosome 18.

PMID- 9662636
TI  - Encyclopedia of the mouse genome VII. Mouse chromosome 19.

PMID- 9662637
TI  - Encyclopedia of the mouse genome VII. Mouse chromosome X.

PMID- 9662638
TI  - Encyclopedia of the mouse genome VII. Mouse chromosome Y.

PMID- 9662639
TI  - Encyclopedia of the mouse genome VII. Master locus list.

PMID- 9662640
TI  - Reference list 

PMID- 9662641
TI  - Maturation of mammalian spermatozoa: modifications of the acrosome and plasma
      membrane leading to fertilization.
AB  - The mammalian spermatozoon is a terminally differentiated cell. Its surface is
      covered by a continuous plasma membrane that is divided into distinct domains in
      which functional molecules are distributed. The acrosome is an internal organelle
      located at the anterior head and contains hydrolytic enzymes. The anterior
      acrosome participates in the acrosome reaction, which is an indispensable event
      during fertilization. These surface domains and the acrosome are formed during
      spermiogenesis, during which associated molecules are transported and organized.
      Many of the molecules thus arranged are functionally immature but gradually
      become mature during epididymal maturation. Some of them are further altered and
      redistributed during the fertilization process and play various roles. Here, the
      sequential changes in the acrosome and plasma membrane during spermatozoan
      maturation are reviewed, particular attention being paid to molecules derived
      from the testis.

PMID- 9662642
TI  - Regulation of gap junction connexins in the endometrium during early pregnancy.
AB  - In mammalian species embryo implantation into uterine tissue is restricted to a
      limited time period, the receptive phase. For successful implantation appropriate
      differentiation of the receptive endometrium is under the control of ovarian
      steroid hormones. In addition, locally acting embryonic signals are needed to
      modulate the maternal environment before invasion of the trophoblast is
      permitted. The expression pattern of gap junction channel proteins, connexins
      (cx), is directly related to this process. In rodents as well as in rabbit and
      humans the receptive endometrium is characterized by a lack of such cell-to-cell
      communication channels. In the rat endometrium cx26 is suppressed in the
      epithelium and cx43 in the stromal compartment by maternal progesterone, a
      phenomenon that can be observed similarly in human endometrium. Experimental
      approaches revealed that both connexin genes react very sensitively to
      progesterone and estrogen treatment. In rat and rabbit connexin expression is
      induced locally in the endometrium in response to the implanting blastocyst. In
      both species this induction of connexins can be mimicked by a traumatic stimulus.
      In conclusion, suppression of connexin expression in the endometrium is a
      characteristic cell biological indication for receptivity in different species.
      The limited induction of direct cell-to-cell communication properties, probably
      due to locally acting blastocyst signals, seems to be a precondition for embryo
      implantation.

PMID- 9662643
TI  - Biochemical identification and tissue-specific expression patterns of keratins in
      the zebrafish Danio rerio.
AB  - We have identified a number of type I and type II keratins in the zebrafish Danio
      rerio by two-dimensional polyacrylamide gel electrophoresis, complementary
      keratin blot-binding assay and immunoblotting. These keratins range from 56 kDa
      to 46 kDa in molecular mass and from pH 6.6 to pH 5.2 in isoelectric point. Type
      II zebrafish keratins exhibit significantly higher molecular masses (56-52 kDa)
      compared with the type I keratins (50-48 kDa), but the isoelectric points show no
      significant difference between the two keratin subclasses (type II: pH 6.0-5.5;
      type I: pH 6.1-5.2). According to their occurrence in various zebrafish tissues,
      the identified keratins can be classified into "E" (epidermal) and "S" (simple
      epithelial) proteins. A panel of monoclonal anti-keratin antibodies has been used
      for immunoblotting of zebrafish cytoskeletal preparations and immunofluorescence
      microscopy of frozen tissue sections. These antibodies have revealed differential
      cytoplasmic expression of keratins; this not only includes epithelia, but also a
      variety of mesenchymally derived cells and tissues. Thus, previously detected
      fundamental differences in keratin expression patterns between higher vertebrates
      and a salmonid, the rainbow trout Oncorhynchus mykiss, also apply between
      vertebrates and the zebrafish, a cyprinid. However, in spite of notable
      similarities, trout and zebrafish keratins differ from each other in many
      details. The present data provide a firm basis from which the application of
      keratins as cell differentiation markers in the well-established genetic model
      organism, the zebrafish, can be developed.

PMID- 9662644
TI  - Postnatal development of GABA- and glycine-like immunoreactivity in the cochlear
      nucleus of the Mongolian gerbil (Meriones unguiculatus).
AB  - The maturation of the morphological substrate for inhibitory interactions was
      investigated in the cochlear nucleus of the gerbil with immunocytochemistry for
      gamma aminobutyric acid (GABA) and glycine on alternating vibratome sections. The
      patterns of immunostaining obtained with both antibodies in the adult closely
      conformed to the general mammalian scheme. Qualitative analyses revealed an age
      related increase in staining intensity and in the relative numbers of
      immunolabelled cells after birth up to the age of 3-4 weeks. As early as birth
      and in all subdivisions of the cochlear nucleus, a few labelled cells and puncta
      in the sections were stained either with the GABA or the glycine antibody.
      Immunoreactive puncta and cells were, however, far less abundant than in the
      adult, and the staining intensity of cells was only weak. The most strikingly
      GABA-immunolabelled cells at birth were the Golgi cells of the granule-cell
      domains. The numbers of weakly GABA- and glycine-immunostained cells of the
      dorsal cochlear nucleus clearly increased between birth and the third postnatal
      week. At approximately the onset of hearing (postnatal day 12-14), some cells of
      the dorsal cochlear nucleus and small cells of the ventral cochlear nucleus
      gained adult-like GABA-staining properties. Almost adult-like labelling intensity
      was observed in glycine-immunoreactive cells of the deep dorsal cochlear nucleus
      and in some small cells of the ventral cochlear nucleus. Puncta staining to both
      antibodies appeared adult-like throughout the cochlear nucleus. About 2 weeks
      after the onset of hearing (at the latest), adult-like staining of all subsets of
      immunoreactive cells occurred throughout the cochlear nucleus in all specimens.

PMID- 9662645
TI  - Effects of glutamate-induced excitotoxicity on calretinin-expressing neuron
      populations in the area postrema of the rat.
AB  - We mapped the distribution of calretinin-immunoreactive neuron populations in a
      circumventricular organ of the rat, the area postrema, and investigated their
      sensitivity to excitotoxic stimuli mediated by subcutaneously administered
      monosodium glutamate. We were specifically interested to ascertain whether the
      presence of calretinin can, per se, confer an in vivo intrinsic resistance for
      area postrema neurons to glutamate excitotoxicity. We found that dense
      populations of calretinin-positive neurons displayed a subregional
      compartmentation in coronal sections of the area postrema along its rostrocaudal
      axis. We demonstrated that calretinin-positive neurons differ in their
      sensitivities to monosodium glutamate depending on their position within the area
      postrema. Neurons in the caudal area postrema were the most sensitive ones, while
      those in the rostral area postrema were spared of degeneration. We conclude that
      calretinin-positive neurons in the area postrema are not uniformly protected
      against glutamate excitotoxicity. It is possible that differences in the local
      concentrations of monosodium glutamate due to regional heterogeneities in density
      and permeability of the capillary bed rather than neuronal expression of
      calretinin account for the observed effects.

PMID- 9662646
TI  - Characterization and localization of two forms of gonadotropin-releasing hormone
      (GnRH) in the spinal cord of the frog Rana ridibunda.
AB  - Two molecular variants of gonadotropin-releasing hormone (GnRH) have been
      previously characterized in the brain of amphibians, i.e., mammalian GnRH (mGnRH)
      and chicken GnRH-II (cGnRH-II). The aim of the present study was to identify the
      molecular forms of gonadotropin-releasing hormone and to localize gonadotropin
      releasing hormone-containing elements in the spinal cord of the frog Rana
      ridibunda using highly specific antisera against mGnRH and cGnRH-II. High
      performance liquid chromatography (HPLC) analysis combined with radioimmunoassay
      (RIA) detection revealed that frog spinal cord extracts contained both mGnRH and
      cGnRH-II. Immunohistochemical labeling revealed that the frog spinal cord was
      devoid of GnRH-containing cell bodies. In contrast, numerous GnRH-immunoreactive
      fibers were observed throughout the entire length of the cord. mGnRH
      immunoreactivity was only detected in the rostral region of the cord and
      consisted of varicose processes located in the vicinity of the central canal.
      cGnRH-II-positive fibers were found throughout the spinal cord, the density of
      immunoreactive processes decreasing gradually toward the caudal region. Two main
      cGnRH-II-positive fiber tracts with a rostrocaudal orientation were observed: a
      relatively dense fiber bundle surrounding the central canal, and a more diffuse
      plexus in the white matter. In addition, short, varicose cGnRH-II-positive
      processes with a radial orientation were present throughout the gray matter.
      These fibers were particularly abundant ventromedially and formed a diffuse
      network that ramified laterally to end in the vicinity of motoneurons. Taken
      together, these data indicate that the frog spinal cord, like the frog brain,
      contains two forms of GnRH. The presence of numerous cGnRH-II-immunoreactive
      fibers in the ventral horn suggests that cGnRH-II may influence the activity of a
      subpopulation of motoneurons.

PMID- 9662647
TI  - Munc-18-1 and cysteine string protein (csp) in pinealocytes of the gerbil pineal
      gland.
AB  - Mammalian pinealocytes contain several synaptic membrane proteins which probably
      play a role in the targeting and exocytosis of secretory vesicles, in particular
      of synaptic-like microvesicles (SLMVs). The latter are considered as the
      endocrine equivalent of neuronal synaptic vesicles. By means of
      immunocytochemical techniques and immunoblot analyses, we now show that two
      further key components of the molecular apparatus regulating neurotransmitter
      release are present in the gerbil pineal gland, i.e., munc-18-1 and cysteine
      string protein (csp). In addition to varicosities of nerve fibres, munc-18-1 and
      csp could be localized to pinealocytes where both proteins were markedly enriched
      in process swellings. When using antibodies against csp for an immunogold
      electron-microscopic study of pinealocytes, gold particles consistently decorated
      profiles of pleomorphic SLMVs. Interestingly, we found that also the cytosolic
      protein munc-18, which is partially recruited to the plasmalemma in neurons, was
      associated to a significant extent with SLMVs of pinealocytes and synaptic
      vesicles of neurons, respectively. This localization implies that munc-18 at
      least partially exerts its regulatory functions while being bound to secretory
      vesicle membranes. Our results indicate that in endocrine cells such as
      pinealocytes the synaptic proteins munc-18-1 and csp play essential roles during
      the life cycle of SLMVs.

PMID- 9662648
TI  - Pleated septate junctions in leech photoreceptors: ultrastructure, arrangement of
      septa, gate and fence functions.
AB  - The leech photoreceptor forms a unicellular epithelium: every cell surrounds an
      extracellular "vacuole" that is connected to the remaining extracellular space
      via narrow clefts containing pleated septate junctions. We analyzed the complete
      structural layout of all septa within the junctional complex in elastic
      brightfield stereo electron micrographs of semithin serial sections from
      photoreceptors infiltrated with colloidal lanthanum. The septa form tortuous
      interseptal corridors that are spatially continuous, and open ended basally and
      apically. Individual septa seem to be impermeable to lanthanum; interseptal
      corridors form the only diffusional pathway for this ion. The junctions form no
      diffusion barrier for the electron-dense tracer Ba2+, but they hinder the
      diffusion of various hydrophilic fluorescent dyes as demonstrated by confocal
      laser scanning microscopy (CLSM) of live cells. Even those dyes that penetrate
      gap junctions do not diffuse beyond the septate junctions. The aqueous diffusion
      pathway within the septal corridors is, therefore, less permeable than the gap
      junctional pore. Our morphological results combined with published
      electrophysiological data suggest that the septa themselves are not completely
      tight for small physiologically relevant ions. We also examined, by CLSM, whether
      the septate junctions create a permeability barrier for the lateral diffusion of
      fluorescent lipophilic dyes incorporated into the peripheral membrane domain.
      AFC16, claimed to remain in the outer membrane leaflet, does not diffuse beyond
      the junctional region, whereas DiIC16, claimed to flip-flop, does. Thus, pleated
      septate junctions, like vertebrate tight junctions, contribute to the maintenance
      of cell polarity.

PMID- 9662649
TI  - Dye-coupling of melanocytes with endothelial cells and pericytes in the cochlea
      of gerbils.
AB  - Intercellular connections via gap junctions in the stria vascularis, which
      constitutes the lateral wall of the cochlear duct, were investigated by the
      Lucifer yellow microinjection method with the aid of a confocal laser microscope.
      The dye injected into an intermediate cell (melanocyte) diffused into capillary
      endothelial cells and pericytes as well as other intermediate cells, basal cells,
      and fibrocytes in the spiral ligament; whereas the dye injected into a marginal
      cell (epithelial cell) was confined to the injected cell. The observation of dye
      coupling between intermediate cells and endothelial cells and pericytes makes
      likely the possibility that these cells work together to play a role in the
      specific function of the stria vascularis (i.e., production of the positive
      endocochlear potential and the endolymph) and adds endothelial cells and
      pericytes to the current "two-cell model" of the stria vascularis.

PMID- 9662650
TI  - Ultrastructural characterization of interstitial cells of Cajal in the rat small
      intestine using control and Ws/Ws mutant rats.
AB  - Interstitial cells in the myenteric plexus and the deep muscular plexus of the
      small intestine of the c-kit mutant rats (Ws/Ws) and their normal siblings (+/+)
      were studied. c-Kit immunoreactivity was detected in two regions corresponding to
      the myenteric plexus and the deep muscular plexus in the jejunum of +/+ rats,
      while no immunoreactivity was detected in Ws/Ws rats. Using electron microscopy,
      two types of gap junction-forming interstitial cells were found in association
      with the myenteric plexus in +/+ rats: one type characterized by a typical
      fibroblastic ultrastructure, and the other characterized by numerous mitochondria
      and less electron-dense cytoplasm. Since the latter were greatly reduced in Ws/Ws
      rats, it was suggested that these cells correspond to c-kit-expressing cells,
      i.e. interstitial cells of Cajal in the myenteric plexus region. In contrast, two
      types of interstitial cells in the region of the deep muscular plexus were
      observed with no difference between +/+ and Ws/Ws rats. Probable interstitial
      cells of Cajal in this region were characterized by a basal lamina and numerous
      caveolae as well as large gap junctions that interconnect with each other and
      with the smooth muscle cells. We concluded that interstitial cells of Cajal in
      the rat intestine are heterogeneous in ultrastructure, c-kit dependency in the
      cell maturation, and functional role.

PMID- 9662651
TI  - Galalpha1-->4Gal-glycans are expressed on myofibrillar associated proteins.
AB  - There is evidence that glycans carrying terminal galactose residues are
      differently expressed in the sarcoplasm of different muscle fiber types. In this
      study monoclonal antibodies directed against P blood group antigens Pk: Galalpha1
      4Galbeta1-4Glcbeta- and P1: Galalpha1-4Galbeta1-4GlcNAcbeta- were used to detect
      terminal alpha-galactosylated glycoconjugates on muscle proteins. Electrotransfer
      of proteins, extracted from human masseter and biceps muscles, to nitrocellulose
      after polyacrylamide gel electrophoresis (PAGE) and incubation with anti-Pk
      (CD77) consistently showed two bands with apparent molecular weights of 66 kDa
      and 64 kDa. In fresh frozen muscle sections from some humans there was
      endothelial reaction with anti-CD77 in capillaries, venules and veins but not in
      arterioles and arteries. In muscle samples from other humans there was no
      staining of endothelial cells. Formalin-fixed human muscle displayed a CD77
      reaction with highest accumulation of reaction product at the periphery of the
      fibers. This may be explained by the presence of Pk glycoconjugates on
      intermediate filaments in muscle fibers. In preparations of cat masseter muscle
      proteins the antibodies against P1Pk antigens reacted with a 170 kDa and a 55 kDa
      band while in preparations of cat biceps brachii only a 55 kDa band was reactive.
      The specificities of the antibodies were investigated by fluorescence-activated
      cell sorter (FACS), alpha- and beta-galactosidase digestion and inhibitory
      sugars. This study indicates that glycans carrying Galalpha1-4Galbeta1- epitopes
      are expressed on myofibrillar associated proteins.

PMID- 9662652
TI  - Internal division of capillaries in rat skeletal muscle in response to chronic
      vasodilator treatment with alpha1-antagonist prazosin.
AB  - Chronic vasodilatation represents a stimulus for capillary growth associated with
      increased luminal shear stress. We have examined the ultrastructure of more than
      2000 capillaries to establish whether the sequence of angiogenesis in response to
      this stimulus is similar to that described during development and under
      pathological circumstances. Administration of the alpha1-blocker prazosin to rats
      for 2 weeks led to a greater capillary length density in extensor hallucis
      proprius muscles without any change in capillary tortuosity: Jv(c,f)=262+/-54
      compared with 350+/-17 mm-2, control compared with prazosin (P<0.002). There were
      obvious signs of endothelial cell (EC) activation after prazosin treatment,
      including an increased proportion of capillaries with rough endoplasmic
      reticulum, large cytoplasmic vacuoles, thickened endothelium and an irregular
      luminal surface. Capillaries from control muscles had a maximum of three ECs in
      cross section, whereas four ECs were noted in 0.8+0.5% of capillaries after 1
      week (n.s.) and 2.5+/-0.9% after 2 weeks (P<0.01) of treatment. This could be due
      to elongation and/or migration of ECs, as cell proliferation has not been
      described at these time points. There was also an increase in the proportion of
      capillaries having a narrow, slit-like lumen (1.7+/-0. 8% of controls; 7.1+/-1.9%
      at 1 week; 8.8+/-2.5% at 2 weeks; P<0.02), some of which were smaller in size
      (less than 2 microm diameter) than in controls (3-5 microm) and/or "seamless",
      i.e. lacking EC junctions. These may represent newly formed vessels. Focal
      discontinuity of the basement membrane and abluminal EC processes were rarely
      seen, and capillary growth by abluminal sprouting appeared to be very infrequent
      (less than 0.001% of profiles). Of more importance was growth starting from the
      luminal side. Significantly more thin cytoplasmic processes were observed
      protruding into the lumen of capillaries after 1 week (47.5+/-6.2%, P<0.001) and
      2 weeks of prazosin (34.2+/-5.5%, P<0.05) than in control vessels (16.7+/-3.9%).
      Some of these traversed the entire lumen and connected with endothelium of the
      opposite side, probably involving membrane fusion, resulting in the appearance of
      a double lumen. Individual capillaries with a complete double lumen were observed
      after 2 weeks' prazosin but comparatively rarely, in only four out of six
      muscles. These findings indicate a pattern of luminal growth which is completely
      different from intussusceptive growth previously described during development,
      and from the abluminal capillary sprouting seen under pathological circumstances.

PMID- 9662653
TI  - Differentiation of muscle-specific proteins in chicken somites as studied by
      immunofluorescence microscopy.
AB  - Fluorescence microscopy of chicken cervical somites revealed that muscle-specific
      proteins began to appear at stage 11 (Hamburger and Hamilton numbering), and the
      onset of the expression of all the proteins examined in the present study had
      occurred by stage 17. Muscle proteins were classified into six groups according
      to the stage of their appearance. Since all these proteins were expressed before
      emergence of nerve fibers in myotomes, switching-on of their synthesis does not
      seem to require neuronal influence. However, since isoproteins other than adult
      muscle types disappeared and diversification of muscle fiber types occurred
      coordinately with the clustering of acetylcholine receptors in cervical muscles,
      switching-off of the synthesis of the nonadult isoforms might have been
      accelerated by the formation of functional neuromuscular junctions. The absence
      of nebulin and C-protein in early stages seems to indicate that these proteins
      are not required for the initial assembly of myofilaments and/or myofibrils.
      Further, this absence might be considered to facilitate exchangeabilities of
      proteins in nascent myofibrils, thereby changing the isoforms to adult types.

PMID- 9662654
TI  - Immunocytochemical and immunochemical study of enamelins, using antibodies
      against porcine 89-kDa enamelin and its N-terminal synthetic peptide, in porcine
      tooth germs.
AB  - Enamelins comprise an important family of the enamel matrix proteins. Porcine
      tooth germs were investigated immunochemically and immunocytochemically using two
      antibodies: a polyclonal antibody raised against the porcine 89-kDa enamelin (89
      E) and an affinity purified anti-peptide antibody against the porcine enamelin
      amino-terminus (EN). Immunochemical analysis of layers of immature enamel from
      the matrix formation stage detected immunopositive protein bands ranging from 10
      kDa to 155 kDa in the outer layer enamel sample irrespective of the antibodies
      used. In contrast, the middle and inner enamel layer mainly contained lower
      molecular weight enamelins. In immunocytochemical analyses of the differentiation
      stage, 89 E stained enamel matrix islands around mineralized collagen fibrils of
      dentin, while EN stained both enamel matrix islands and stippled material. At the
      matrix formation stage, both antibodies intensely stained enamel prisms located
      in the outer layer. In the inner layer, 89 E moderately stained enamel matrix
      homogeneously, while EN primarily stained the prism sheath. The intense
      immunoreaction over the surface layer of enamel matrix at the matrix formation
      stage, following staining with 89 E and EN, disappeared by the end of the
      transition stage and the early maturation stage, respectively. The Golgi
      apparatus and secretory granules in the ameloblasts from the late differentiation
      stage to the transition stage were immunostained by both antibodies. These
      results suggest that expression of enamelin continues from late differentiation
      to the transition stage and the cleavage of N-terminal region of enamelin occurs
      soon after secretion. Some enamelin degradation products, which apparently have
      no affinity for hydroxyapatite crystals, concentrate in the prism sheaths during
      enamel maturation.

PMID- 9662655
TI  - Cytological and enzyme-histochemical investigations on the digestive organs of
      Nautilus pompilius (Cephalopoda, Tetrabranchiata).
AB  - The foregut, stomach, caecum, midgut, and rectum of the digestive tract of
      Nautilus pompilius L.were investigated with ultrastructural and enzyme
      cytological methods. Three different cell types were identified within the lamina
      epithelialis mucosae: main cells, goblet cells, and cells with secretory
      granules. The main cell type is the epithelial cell with microvilli, a basal
      nucleus surrounded by dictyosomes, rough endoplasmic reticulum, mitochondria, and
      electron-dense granules identified as lysosomes in the apical part of the cell.
      In the caecum this cell type contains endosymbiotic bacteria. The presence of
      endocytotic vesicles and the storage of lipids in the caecum indicate that this
      organ is involved in the process of absorption. In the caecum and the
      longitudinal groove of the rectum the main cells are, in addition, ciliated,
      facilitating the transport of food particles and faeces. Two types of goblet
      cells are found in all organs except in the stomach, forming a gliding path for
      food particles and protecting the epithelium. In the foregut and rectum, cells
      with electron-dense granules were recognized as the third type. The conspicuous
      secretory cells of the rectum represent a delimited rectal gland; its possible
      biological function is discussed. The tunica muscularis in all organs of the
      digestive tract consists of obliquely striated muscle cells innervated by axons
      containing transparent, osmiophilic and dense-cored vesicles. Positive reactions
      for acid and alkaline phosphatase, monoamine oxidase, beta-glucuronidase, and
      trypsin- and chymotrypsin-like enzymes are localized in the lamina epithelialis
      mucosae.

PMID- 9662656
TI  - The effect of retinoic acid on the re-establishment of differentiated hepatocyte
      phenotype in primary culture.
AB  - The usefulness of cultured hepatocytes is limited by the gradual loss of their
      typical physiological functions that occurs in vitro, mainly due to the absence
      of microenviromental conditions found in vivo. In this study we describe the
      effect of retinoic acid on the re-establishment of morphological characteristics
      and on the reorganization of the cytoskeletal network in cultured rat
      hepatocytes. Results obtained demonstrate that retinoic acid can influence
      hepatocyte differentiation, as regards the recovery of cell polarity, polyhedric
      shape and reformation of bile canaliculi and junctional complexes. The main
      target of this action appears to be the cytoarchitecture of cytoskeletal
      components, particularly cytokeratin filaments, which regain the configuration
      present in intact liver. The reorganization of the intermediate filaments does
      not seem to be dependent on the induction of higher levels of cytokeratin
      proteins, but rather appears to be due to post-translational regulation. The
      effect of retinoic acid on the cytoskeletal organization could determine the
      stabilization of intercellular contacts by means of junctions, leading to the
      appearance of morpho-functional characteristics typical of well-differentiated
      hepatocytes.

PMID- 9662657
TI  - Convoluted cords, a new nuclear body in spermatocytes and spermatids of the
      rabbit.
AB  - The convoluted cords present in the nuclei of rabbit primary spermatocytes and
      spermatids differ from previously described nuclear bodies. They are composed of
      proteic strands decorated with granules and, in most cases, are embedded in
      clusters of interchromatin granules. They are partly sensitive to trypsin and can
      be visualised with protein-specific stains. The decorating granules are similar
      in size and aspect to interchromatin granules. However, only the latter are
      continuously immunolabelled with anti-snRNPs (small ribonucleoproteins)
      antibodies during spermatogenesis. The complexity and organisation of the
      convoluted cords are modified specifically during cell differentiation. They
      might be involved in the storage, transport and release of interchromatin
      granules in male germ cells.

PMID- 9662658
TI  - Thyroid hormone-induced chondrocyte terminal differentiation in rat femur organ
      culture.
AB  - Thyroid hormone plays a role in skeletal maturation. The present study was
      undertaken to investigate the effect of thyroid hormone on growth and maturation
      of the epiphyseal cartilage in the rat femur organ culture system. The femora
      increased in both weight and size over time in culture in the absence of serum.
      The growth rate was suppressed by thyroxine treatment. Thyroxine induced
      chondrocyte hypertrophy in the area adjacent to the articular surface in the
      femoral condyle. In this area, the expression of type X collagen, a marker of
      chondrocyte terminal differentiation, was detected after 21 days in culture by
      immunohistochemistry and reverse transcription/polymerase chain reaction. These
      data suggest that thyroxine suppresses cartilage growth by stimulating
      chondrocyte terminal differentiation.

PMID- 9662659
TI  - A sponge/dinoflagellate association in the haplosclerid sponge Haliclona sp.:
      cellular origin of cytotoxic alkaloids by percoll density gradient fractionation.
AB  - Light-microscopic and electron-microscopic studies of the tropical marine sponge
      Haliclona sp. (Order: Haplosclerida; Family: Haliclonidae) from Heron Island,
      Great Barrier Reef, have revealed that this sponge is characterized by the
      presence of dinoflagellates and by nematocysts. The dinoflagellates are 7-10
      micrometer in size, intracellular, and contain a pyrenoid with a single stalk,
      whereas the single chloroplast is branched, curved, and lacks grana. Mitochondria
      are present, and the nucleus is oval and has distinct chromosomal structure. The
      dinoflagellates are morphologically similar to Symbiodinium microadriaticum, the
      common intracellular symbiont of corals, although more detailed biochemical and
      molecular studies are required to provide a precise taxonomic assignment. The
      major sponge cell types found in Haliclona sp. are spongocytes, choanocytes, and
      archaeocytes; groups of dinoflagellates are enclosed within large vacuoles in the
      archaeocytes. The occurrence of dinoflagellates in marine sponges has previously
      been thought to be restricted to a small group of sponges including the
      excavating hadromerid sponges; the dinoflagellates in these sponges are usually
      referred to as symbionts. The role of the dinoflagellates present in Haliclona
      sp. as a genuine symbiotic partner requires experimental investigation. The
      sponge grows on coral substrates, from which it may acquire the nematocysts, and
      shows features, such as mucus production, which are typical of some excavating
      sponges. The cytotoxic alkaloids, haliclonacyclamines A and B, associated with
      Haliclona sp. are shown by Percoll density gradient fractionation to be localized
      within the sponge cells rather than the dinoflagellates. The ability to
      synthesize bioactive compounds such as the haliclonacyclamines may help Haliclona
      sp. to preserve its remarkable ecological niche.

PMID- 9662660
TI  - Our challenge for the next millennium.

PMID- 9662661
TI  - Reliability of the anteroposterior axis and the posterior condylar axis for
      determining rotational alignment of the femoral component in total knee
      arthroplasty.
AB  - We examined the reliability of the anteroposterior and posterior condylar axes
      for determining rotational alignment of the femoral component in total knee
      arthroplasty (TKA). A computed tomography scan was taken at the level of the
      femoral epicondyle in 84 knees (27 varus knees with medial femorotibial arthritis
      (FT-OA) in 26 patients, 17 knees with patellofemoral arthritis in 14 patients,
      and 40 normal knees in 40 volunteers). On the image, an anteroposterior axis, a
      line perpendicular to the anteroposterior axis, an epicondylar axis and a
      posterior condylar axis were drawn, and the relationship between the three axes
      was assessed. The mean values for the 84 knees were evaluated, and the posterior
      condylar axis was 6.0 degrees +/- 2.4 degrees internally rotated relative to the
      epicondylar axis, while the line perpendicular to the anteroposterior axis was
      1.4 degrees +/- 3.3 degrees internally rotated relative to the epicondylar axis.
      The internal rotation angle of the posterior condylar axis relative to the
      epicondylar axis was 6.2 degrees +/- 1.9 degrees in the knees with medial
      femorotibial arthritis, 6.4 degrees +/- 2.4 degrees in the knees with
      patellofemoral arthritis, and 5.8 degrees +/- 2.7 degrees in the normal knees,
      showing consistent values in normal and osteoarthritic knees. The internal
      rotation angle of the line perpendicular to the anteroposterior axis relative to
      the epicondylar axis was 0.1 degrees +/- 3.3 degrees, 1.3 degrees +/- 3. 3
      degrees, and 2.3 degrees +/- 3.1 degrees in the three groups, respectively (i.e.,
      there were significant differences between the medial FT-OA knees and the normal
      knees). The results demonstrated that the anteroposterior axis was rotated
      externally to a significant degree in medial FT-OA knees and was less reliable
      than the posterior condylar axis for use in alignment for TKA on medial FT-OA
      knees.

PMID- 9662662
TI  - Interlocking nailing of humeral shaft fractures.
AB  - : In this retrospective study 48 humeral shaft fractures in 48 patients were
      operated on using the Seidel interlocking nail. The length of follow-up ranged
      from 6 to 60 months (median, 26 months). The treatment of fractures was
      satisfactory with the Seidel nail, but we emphasize the importance of
      countersinking the tip of the nail into the humeral head to avoid impingement. In
      5 of 12 patients with non-unions, the procedure failed, and we found that the
      distal locking seemed to be inadequate. Pathological fractures (i.e., those
      caused by metastatic tumors) were all efficiently treated with the Seidel nail.

PMID- 9662663
TI  - Prevalence of impingement in explanted Charnley acetabular components.
AB  - : Impingement of the femoral neck against the rim of the socket bore has often
      been cited as one of the contributory factors in the acetabular loosening
      process. However, there has been little research on its clinical prevalence or on
      the effects of both linear wear and the diameter of the femoral neck. With this
      aim in mind, 74 Charnley prostheses were examined after being removed at revision
      surgery and the sockets interrogated for evidence of impingement. The probability
      of impingement was assessed using logistic regression analysis. A strong positive
      association was observed between penetration depth and impingement (chi2 = 12.8;
      P = 0.0004) regardless of differences in the femoral neck diameter. Further, the
      introduction of femoral components which comprised a reduced diameter neck had a
      positive effect, in that the 50% probability of impingement occurred at
      approximately 2 mm of penetration. For those components with standard necks, the
      50% probability of impingement occurred at zero mm of penetration. If impingement
      is a problem then a reduced diameter neck would appear to be a solution in
      cutting rates of long-term loosening. However, whether or not this reduction in
      rim damage, and therefore impingement, is clinically significant in terms of
      loosening can only be fully assessed from long-term survival analysis and
      comparison with autopsy retrieved specimens.

PMID- 9662664
TI  - Pathology study of rabbit calf muscles after repeated compression.
AB  - : To elucidate the pathogenesis of chronic compartment syndrome, we examined
      pathological changes in the soleus (red) and extensor digitorum longus (EDL;
      white) muscles in Japanese white rabbits after repeated compression with a
      pneumatic tourniquet. Repeated tourniquet compression via cuff inflation was
      carried out on the rabbits, calves daily, for 2 h, then stopped for 30 min, and
      then applied for another 2 h. The contralateral hindlimb, which was not
      compressed, served as a control. Animals were allocated to 15 groups, with
      pressures of 40, 80, and 120 mmHg for periods of 1 day, 3 days, 1 week, 2 weeks,
      and 4 weeks. Skeletal muscle specimens in each group were studied by
      histopathological and histochemical (ATPase) methods. After compression for 1
      day, regardless of pressure, and compression for 3 days in the 40-mmHg pressure
      group, edematous changes in regions with mild inflammation and increases in fiber
      diameter were observed in the muscles. After compression for 3 days in the 80-
      and 120-mmHg pressure groups, and after 1, 2, or 4 weeks in the 40-mmHg pressure
      group, a few necrotic fibers and scattered fibers with some mononuclear cell
      infiltrates indicative of early-stage necrosis were detected. In the groups with
      80 or 120 mmHg pressure for 1, 2, or 4 weeks, muscle fibers exhibited marked
      degenerative changes, which were more pronounced in the 120-mmHg group than in
      the 80-mmHg group. The pathological changes were more pronounced in the soleus
      than in the EDL muscles, indicating that these two muscles differed in
      sensitivity to repeated compression. Additionally, average muscle wet weight and
      average fiber diameter for both types of muscle were increased in the 1-day and 3
      day compression groups and decreased in the 1-week, 2-week, and 4-week
      compression groups. These findings clearly differ from those of previously
      reported single-compression experiments. Our findings indicate that repeated
      compression may cause serious muscle degeneration, particularly in red muscles.

PMID- 9662665
TI  - Bilateral Kienbock's disease.
AB  - Bilateral Kienbock's disease is very rare. We report here five cases of bilateral
      Kienbock's disease in the wrist. Of the five patients, two were manual workers
      and one was a housewife. The two other patients were retired and had received
      steroids for long periods to control autoimmune disease. The mean ulnar variance
      was 1. 8 (0-5) mm, and none of the patients had negative variance, indicating
      that negative ulnar variance was not a major risk factor for the development of
      bilateral Kienbock's disease.

PMID- 9662666
TI  - Primary iliopsoas abscess successfully treated by ultrasonographically guided
      percutaneous drainage.
AB  - We report a case of primary iliopsoas abscess successfully treated by
      ultrasonographically guided percutaneous drainage. A 56-year-old man presented at
      our hospital with lumbago, right-sided back pain, fever (temperature 38.5 degrees
      C) and chills. On physical examination, we found dark red skin, swelling, and
      tenderness localized at the right side at the back of his waist. Laboratory
      examination showed leukocytosis (white blood cell count 9700/mm3) with a leftward
      shift and elevated C-reactive protein (5.2 mg/dl). Ultrasonography (US), computed
      tomography (CT), and magnetic resonance imaging revealed a hypodense lesion in
      the right iliopsoas muscle extending to the subcutaneous tissue. About 50 ml of
      thick yellow pus was obtained by ultrasonographically guided aspiration drainage.
      A drain catheter was inserted in the abscess cavity. Laboratory findings improved
      and clinical symptoms abated rapidly after drainage. On the twenty-first day
      after drainage, US and CT showed that the abscess was no longer present. The
      patient was discharged after 32 days of hospitalization. As possible primary
      diseases causing iliopsoas abscess, such as digestive tract disease,
      tuberculosis, and osteomyelitis, were not found, we diagnosed the disease as
      primary iliopsoas abscess. Although surgical drainage has been performed in most
      reported cases of iliopsoas abscess, this case report shows that
      ultrasonographically guided percutaneous drainage is also effective for treating
      primary iliopsoas abscess if it is diagnosed early enough.

PMID- 9662667
TI  - Clinical diagnosis of soft tissue tumors.
AB  - In the clinical diagnosis of a soft tissue tumor, it is important to determine
      whether the lesion is malignant as soon as possible. To establish such a
      diagnosis we perform aspiration cytology and needle biopsy simultaneously with
      computed radiography (CR) and echosonogram at the first visit. After the first
      day's investigations, it is usually possible to select the surgical procedures
      based on the working diagnosis in almost all patients. When the lesion is clearly
      benign by diagnosis, excision can be performed. For large lesions or lesions that
      are suspected to be malignant, CT, magnetic resonance imaging , isotope
      investigation, and arteriography are also performed, effectively providing
      precision in an already established diagnosis. These imaging findings are useful
      for establishing a surgical plan by anticipating the surgical line of the safety
      margin. For these few patients in whom the diagnosis still remains uncertain or
      when preoperative treatment is planned, an incisional or excisional biopsy may be
      necessary to establish the final diagnosis. When preoperative treatment is
      performed, the effectiveness of this treatment can be evaluated by medical
      imaging.

PMID- 9662668
TI  - Skeletal muscle abnormalities in patients with COPD: contribution to exercise
      intolerance.
AB  - Exercise intolerance in COPD patients appears to be in part because of skeletal
      muscle dysfunction. Studies using biopsy techniques and magnetic resonance
      spectroscopy have demonstrated changes in enzyme activities and metabolism that
      indicate reduced oxidative capacity in the peripheral muscles of these patients.
      Regarding the respiratory muscles, the biochemical characteristics have been
      studied in only a few works and the results seem to depend on the specific muscle
      group studied. Several factors, such as hypoxemia, nutritional status,
      pharmacological treatment, and deconditioning, may be responsible for these
      skeletal muscle abnormalities. This brief review describes the changes in
      peripheral and respiratory muscles in COPD patients based on data from the
      literature. The causes of these muscle abnormalities, their contribution to
      exercise intolerance, and the effects of training are then discussed. We conclude
      with suggested directions for future investigation using contemporary noninvasive
      technologies.

PMID- 9662669
TI  - Effects of exercise and estrogen therapy on lipid profiles of postmenopausal
      women.
AB  - PURPOSE: We compared the effects of aerobic exercise training on lipid and
      lipoprotein levels in 18 postmenopausal women who were (N = 8) or were not (N =
      10) receiving estrogen replacement therapy (ERT). METHODS: Each group was tested
      for lipids, diet recall and VO2max before and after a 12 wk exercise program,
      consisting of 30-50 min of an aerobic activity at 75-85% of VO2max, 3-4 sessions
      per week. RESULTS: Both groups increased VO2max by 8% and neither group changed
      their diet. The ERT group had higher levels of triglycerides and lower levels of
      low density lipoprotein (LDL-C) (P < 0.01) before training. There were no mean
      group changes in any of the lipid variables with training. However, individual
      changes in LDL-C and Total Cholesterol (TC) were strongly related to baseline
      weight in the nonestrogen group (r = 109.91, r = -0.82) but not in ERT (r = 
      0.30, r = -0.51). Subsequently, all subjects were redivided into two groups based
      on BMI (< or = 27 or > or = 27) regardless of ERT status. TC decreased
      significantly (P < 0.05) in the < or = 27 BMI group. CONCLUSIONS: Exercise
      training had little effect on the lipid profiles of the ERT and the nonestrogen
      groups, but body weight seems to be a modulating factor. Heavier subjects did not
      respond as favorably to 12 wk of exercise training as postmenopausal women with
      less body mass, regardless of the presence of exogenous estrogen.

PMID- 9662670
TI  - Effects of lower body pressure changes on pulmonary function.
AB  - PURPOSE: During and following exercise there are a number of changes in pulmonary
      function, among which is a decrease in forced vital capacity (FVC). Several
      potential mechanisms may explain this decreased FVC, including an exercise
      induced increase in thoracic blood volume. METHODS: We tested the hypothesis that
      altered thoracic blood volume alone, as produced by the application of 30 mm Hg
      lower body negative (LBNP) or positive pressure (LBPP) for 5 min, would change
      FVC and forced expiratory volume in 1 s (FEV1.0). Further, we tested whether the
      changes in pulmonary function were related to initial lung volume and whether the
      lower body pressure changes led to an altered lung compliance as measured by
      static pressure-volume curves. RESULTS: Results indicated that with LBNP, FVC,
      and FEV1.0 were significantly increased by approximately 0.15 L and 0.18 L,
      respectively. When LBPP was applied, FVC and FEV1.0 were decreased by
      approximately 0.18 and 0.14 L, respectively. The increase in FVC with LBNP was
      significantly related to the original FVC (r = 0.66, P < 0.05). There was no
      significant correlation between the increase in FEV1.0 and the original FEV1.0 (r
      = 0.48, P > 0.05). Pulmonary compliance was not changed significantly by the
      application of LBPP. CONCLUSIONS: These results suggest that part of the change
      in pulmonary function following heavy exercise is related to an increased
      thoracic blood volume. The lack of change in lung compliance suggests that the
      effect of altered thoracic blood volume is to displace air and not to change the
      mechanical properties of the lungs.

PMID- 9662671
TI  - Cardiovascular function following reduced aerobic activity.
AB  - PURPOSE: The aim of this study was to test the hypothesis that a sustained
      reduction of physical activity (deconditioning) would alter the cardiovascular
      regulatory function. METHODS: Nineteen young, healthy volunteers participated in
      physical deconditioning for a period of 8 wk. Before (pre) and following (post)
      physical deconditioning, the responses of heart rate (HR), mean arterial pressure
      (MAP, measured by Finapres), central venous pressure (CVP), stroke volume (SV,
      Doppler), and forearm blood flow (FBF, plethysmography) were determined during
      lower body negative pressure (LBNP). The carotid baroreflex (CBR) function was
      assessed using a train of pulsatile neck pressure (NP) and suction, and the
      aortic baroreflex control of HR was assessed during steady-state phenylephrine
      (PE) infusion superimposed by LBNP and NP to counteract the PE increased CVP and
      carotid sinus pressure, respectively. RESULTS: Active physical deconditioning
      significantly decreased maximal oxygen uptake (-7%) and LBNP tolerance (-13%)
      without a change in baseline hemodynamics. Plasma volume (-3% at P = 0.135),
      determined by Evans Blue dilution, and blood volume (-4% at P = 0.107) were not
      significantly altered. During LBNP -20 to -50 torr, there was a significantly
      greater drop of SV per unit decrease in CVP in the post- (14.7 +/- 1.6%/mm Hg)
      than predeconditioning (11.2 +/- 0.7%/mm Hg) test accompanied by a greater
      tachycardia. Deconditioning increased the aortic baroreflex sensitivity (pre vs
      post: -0.61 +/- 0.12 vs -0.84 +/- 0.14 bpm.mm-1 Hg, P = 0.009) and the slope of
      forearm vascular resistance (calculated from [MAP-CVP]/FBF) to CVP (-2.75 +/-
      0.26 vs -4.94 +/- 0.97 PRU/mm Hg, P = 0.086). However, neither the CBR-HR (-0.28
      +/- 0.03 VS -0.39 +/- 0.10 bpm.mm-1 Hg) nor the CBR-MAP (-0.37 +/- 0.16 vs -0.25
      +/- 0.07 mm Hg/mm Hg) gains were statistically different between pre- and
      postdeconditioning. CONCLUSIONS: We concluded that the functional modification of
      the cardiac pressure-volume relationship resulted in the reduced LBNP tolerance,
      despite the accentuated aortic and cardiopulmonary baroreflex function following
      deconditioning.

PMID- 9662672
TI  - Alanine and glutamine kinetics at rest and during exercise in humans.
AB  - PURPOSE: The purpose of this study was to quantify both alanine and glutamine
      kinetics during exercise of moderate intensity to determine the sum total of
      alanine and glutamine flux. METHODS: Tracer methods were used to quantify alanine
      and glutamine rates of appearance (Ra) in plasma at rest and during 180 min of
      approximately 45% VO2max treadmill exercise in six normal volunteers (25 +/- 2
      yr, 68 +/- 2.5 kg, VO2max 43 +/- 2.4 mL.min-1.kg-1; means +/- SE). Bolus
      injections (N = 3) or primed-constant infusions (N = 3) of 2H5-glutamine and 3
      13C-alanine were given at rest on 1 d and 10-15 min after the onset of exercise
      on a separate day less than 2 wk later. Plasma enrichment decay curves and
      plateau enrichments were used to estimate alanine and glutamine kinetics.
      RESULTS: Whereas alanine Ra increased significantly from rest to exercise (5.72
      +/- 0.31 vs 13.5 +/- 1.9 mumol.min-1.kg-1, respectively; P < 0.01), glutamine Ra
      was not significantly altered by exercise (6.11 +/- 0.44 and 6.40 +/- 0.69
      mumol.min-1.kg-1 at rest and during exercise, respectively). The total of alanine
      and glutamine flux increased from 17.93 +/- 0.88 to 25.98 +/- 3.04 (P < 0.05).
      CONCLUSIONS: Since most muscle amino-N is released as alanine and glutamine,
      these findings provide strong evidence that amino-N delivery from muscle to the
      liver is increased during exercise. In addition, it appears that alanine, rather
      than glutamine, is the predominant N carrier involved in the transfer of N from
      muscle to the liver during moderate intensity exercise.

PMID- 9662673
TI  - Creatine kinase release and clearance using MM variants following repeated bouts
      of eccentric exercise.
AB  - PURPOSE: This study investigated the release and clearance of plasma CK-MM
      (muscle) isoforms following two bouts of eccentric exercise to determine whether
      enhanced enzyme clearance could in part explain the blunted creatine kinase (CK)
      response to a second bout of exercise. METHODS: Nonweight trained college-aged
      male subjects performed both bouts of 50 forced lengthening contractions of the
      forearm flexor muscles separated by 6 d either with the same arm (CON; N = 4) or
      with one arm followed by the contralateral arm (EXP; N = 4). Range of motion, arm
      circumference, maximal isometric strength, perceived muscle soreness, total CK
      (TCK), and MM variants were assessed. Each MM isoform was measured as a
      percentage of TCK activity and in absolute activity (IU.L-1) following
      isoelectric separation and densitometry. The MM1:MM3 ratio, calculated from
      absolute concentrations, was used to indicate periods of release and clearance.
      RESULTS: Non-CK criterion measures indicated that similar damage occurred in both
      arms for EXP (P > 0.05), whereas CON exhibited a blunted response on bout 2 (P <
      0.01). Postbout 1, TCK peaked at 96 h for CON (3530 +/- 927 IU.L-1) and EXP (6683
      +/- 433 IU.L-1) (P < 0.01). Postbout 2, CON TCK showed no additional increase;
      however, a second rise in EXP TCK reached its highest point by day 5 (3602 +/-
      1190 IU.L-1). Expectedly, %MM1 and the MM1: MM3 ratio were increased after bout 1
      in both groups (P < 0.01). New CK release was observed postbout 2 in both groups
      as indicated by an increase in %MM1 (P < 0.01), despite no increase in TCK after
      bout 2 for CON and a smaller CK response for EXP. CONCLUSION: Accelerated
      clearance of CK seems to be one factor contributing to the blunted response of
      this enzyme following a repeated bout of exercise.

PMID- 9662674
TI  - Gender differences in FFM accumulation and architectural characteristics of
      muscle.
AB  - PURPOSE: The purpose of this study was to gain insight into the skeletal muscle
      development potential in women and to evaluate the contribution of muscle
      pennation angle (PANG) and fascicle length to gender differences in muscle size
      or FFM accumulation. METHODS: Skeletal muscle architectural characteristics and
      FFM were studied in 29 strength-trained female and 22 age- and height-matched
      male college athletes. Muscle thickness (MTH) was measured by B-mode ultrasound
      at 13 anatomical sites. Isolated MTH and PANG of the triceps long head (TL),
      vastus lateralis (VL), and gastrocnemius medialis (MG) muscles were measured in
      vivo, and fascicle length was estimated. RESULTS: Six female athletes had more
      than 60 kg of FFM, with the largest being 82.1 kg. In general, male athletes had
      a significantly greater FFM and MTH at all sites except for the anterior thigh.
      Isolated MTH and PANG of the TL, VL, and MG were greater in males. There were no
      gender differences in limb length or fascicle length of the three isolated
      muscles. A significant correlation was observed between MTH and PANG for TL (r =
      0.84) and MG (r = 0.41), but not for VL. CONCLUSIONS: In contrast to previous
      estimates, we conclude that the theoretical upper limit of FFM accumulation and
      FFM-to-height ratio in women is greater than 80 kg and 0.44 kg.cm-1,
      respectively. Gender differences in PANG appear to be related to differences in
      muscle size (MTH) and do not appear to contribute independently to the gender
      difference in FFM.

PMID- 9662675
TI  - Validity and reliability in a Flemish population of the WHO-MONICA Optional Study
      of Physical Activity Questionnaire.
AB  - PURPOSE: This study assessed the validity and reliability of a self-administered
      physical activity questionnaire used in the WHO-MONICA project. METHODS: Subjects
      (N = 167) were physical education and physical therapy alumni. The questionnaire
      (MOSPA-Q) covers a 1-yr period and measures the average weekly time and energy
      expenditure spent in one's occupation, transport-related activities, household
      chores, and leisure time activities. Test-retest reliability was reported as the
      intra-class correlation between calculated time or energy expenditure in
      different questionnaire items determined from two MOSPA-Q administrations.
      Validity was assessed using biometrical and physiological parameters as criterion
      measures. RESULTS: Test-retest reliability ranged from 0.45 to 0.92 with the
      highest correlation coefficients obtained for the leisure time physical
      activities. The correlation between calculated daily total energy expenditure
      (TEE, Kcal.d-1) and lean body mass was 0.53 (P < 0.001). The correlation between
      energy expenditure in leisure time activities (Kcal.wk-1) and VO2peak was 0.44.
      CONCLUSIONS: The MOSPA-Q provides a relatively valid and reliable estimate of
      physical activity.

PMID- 9662676
TI  - Six-month physical activity and fitness changes in Project Active, a randomized
      trial.
AB  - PURPOSE: Project Active is a randomized clinical trial (N = 235) comparing a
      lifestyle physical activity program with a structured exercise program in
      changing physical activity (total energy expenditure [kcal.kg-1.d-1]) and
      cardiorespiratory fitness (VO2peak in mL.kg-1.min-1). METHODS: Sedentary but
      healthy adults (N = 235) aged 35-60 years received 6 months of intensive
      intervention. RESULTS: Analysis of covariance (ANCOVA), adjusting for baseline
      measure, age, gender, body mass index (BMI), cohort, and ethnicity, showed that
      at 6 months both lifestyle and structured groups significantly increased energy
      expenditure over baseline (P < 0.001). The mean increases +/- SE, 1.53 +/- 0.19
      kcal.kg-1.d-1 for the lifestyle group and 1.34 +/- 0.20 kcal.kg-1 d-1 for the
      structured group, were not significantly different between groups (P = 0.49). For
      cardiorespiratory fitness, both groups had significant increases from baseline (P
      < 0.001). Mean increases +/- SE were 1.58 +/- 0.33 mL.kg-1.min-1 and 3.64 +/-
      0.33 mL.kg-1.min-1 for the lifestyle and structured groups, respectively. This
      was significantly greater in the structured group (P < 0.001). We also studied
      changes in intensity of physical activity. Both groups significantly increased
      moderate intensity activity from baseline, but the increase was significantly
      greater in the lifestyle group than the structured group (P = 0.02). In contrast,
      the structured group increased its hard activity more than the lifestyle group,
      but the difference was not significantly different (P = 0.02). In contrast, the
      structured group increased its hard increased (P < 0.01) for both groups by 0.25
      kcal.kg-1.d-1. CONCLUSION: Both intervention approaches are effective for
      increasing physical activity and fitness over a 6-month period in initially
      sedentary men and women.

PMID- 9662677
TI  - The context of the Activity Counseling Trial.

PMID- 9662678
TI  - Overview of the Activity Counseling Trial (ACT) intervention for promoting
      physical activity in primary health care settings. Activity Counseling Trial
      Research Group.
AB  - Counseling by health care providers has the potential to increase physical
      activity in sedentary patients, yet few studies have tested interventions for
      physical activity counseling delivered in health care settings. The Activity
      Counseling Trial (ACT) is a 5-yr randomized clinical trial to evaluate the
      efficacy of two primary care, practice-based physical activity behavioral
      interventions relative to a standard care control condition. A total of 874
      sedentary men and women, 35-75 yr of age, have been recruited from primary care
      physician offices at three clinical centers for 2 yr of participation. They were
      randomly assigned to one of three experimental conditions that vary, in a
      hierarchical fashion, by level of counseling intensity and resource requirements.
      The interventions, which are based on social cognitive theory and the
      transtheoretical model, are designed to alter empirically based psychosocial
      mediators that are known to be associated with physical activity. The present
      paper describes the theoretical background of the intervention, the intervention
      methods, and intervention training and quality control procedures.

PMID- 9662679
TI  - Activity Counseling Trial (ACT): rationale, design, and methods. Activity
      Counseling Trial Research Group.
AB  - The Activity Counseling Trial (ACT) is a multicenter, randomized controlled trial
      to evaluate the effectiveness of interventions to promote physical activity in
      the primary health care setting. ACT has recruited, evaluated, and randomized 874
      men and women 35-75 yr of age who are patients of primary care physicians.
      Participants were assigned to one of three educational interventions that differ
      in amount of interpersonal contact and resources required: standard care control,
      staff-assisted intervention, or staff-counseling intervention. The study is
      designed to provide 90% power in both men and women to detect a 1.1 kcal.kg-1.day
      1 difference in total daily energy expenditure between any two treatment groups,
      and over 90% power to detect a 7% increase in maximal oxygen uptake, the two
      primary outcomes. Primary analyses will compare study groups on mean outcome
      measures at 24 months post-randomization, be adjusted for the baseline value of
      the outcome measure and for multiple comparisons, and be conducted separately for
      men and women. Secondary outcomes include comparisons between interventions at 24
      months of factors related to cardiovascular disease (blood lipids/lipoproteins,
      blood pressure, body composition, plasma insulin, fibrinogen, dietary intake,
      smoking, heart rate variability), psychosocial effect, and cost-effectiveness,
      and at 6 months for primary outcome measures. ACT is the first large-scale
      behavioral intervention study of physical activity counseling in a clinical
      setting, includes a generalizable sample of adult men and women and of clinical
      setting, and examines long-term (24 months) effects. ACT has the potential to
      make substantial contributions to the understanding of how to promote physical
      activity in the primary health care setting.

PMID- 9662680
TI  - Exercise-induced anxiolysis: a test of the "time out" hypothesis in high anxious
      females.
AB  - PURPOSE: One purpose was to test the hypothesis that anxiety reductions following
      exercise are caused by a "time out" from daily cares and worries, and the second
      purpose was to document the magnitude of the change in state anxiety after
      exercise in high trait anxious females. METHODS: Anxious women (N = 14) completed
      four randomly ordered conditions: Exercise Only, 20 min of cycling (40% of
      VO2peak) followed by 20 min of recovery; Study Only, 40 min of studying while
      sitting on a cycle ergometer; Exercise/Study, 20 min of cycling (40% of VO2peak)
      while studying followed by 20 min of studying while sitting on the cycle
      ergometer; and Control, sitting quietly on an ergometer for 40 min. RESULTS:
      State anxiety was assessed before and after each condition. State anxiety was
      reduced following the Exercise Only condition (mean raw change score +/- 95%
      confidence interval (CI) of 4.3 +/- 3.5; t = 2.3, P = 0.04, d = 0.52). The 95% CI
      did not include zero after adjusting for precondition anxiety scores (adjusted
      change +/- 95% CI of 3.3 +/- 3.2). CONCLUSIONS: Because the reduction in state
      anxiety following exercise was blocked in the Exercise/Study condition (t = 
      0.05, P = 0.97, d = 0.01) and the associated CIs included zero (unadjusted 0.1 +/
      3.4, adjusted 0.8 +/- 3.2), the findings support the hypothesis that anxiety
      reductions following exercise occur because exercise affords individuals a time
      out from daily worries.

PMID- 9662681
TI  - Repeated bouts of exercise alter the blood lactate-RPE relation.
AB  - PURPOSE: To examine the effects of repeated bouts of exercise on the blood
      lactate [HLa]-ratings of perceived exertion (RPE) relation. METHODS: Six
      moderately trained males were studied on two occasions: a sequential exercise
      bouts day (SEB: 1000 h, 1130 h, and 1300 h) and a delayed exercise bouts day
      (DEB: 1000 h, 1400 h, and 1800 h). Each of the three exercise bouts within a
      given condition were 30 min in duration at the power output (PO) associated with
      70% of VO2peak on a cycle ergometer. A standardized meal was provided at 0600 h.
      VO2, PO, HR, and RER were recorded every min during exercise and blood [HLa] and
      RPE were measured every 5 min during exercise. RESULTS: A 2 x 3 analysis of
      variance with repeated measures revealed that blood [HLa] decreased significantly
      with each repeated exercise bout (X +/- SEM: bout 1: SEB = 3.5 (0.3), DEB = 3.8
      (0.4); bout 2: SEB = 2.6 (0.3), DEB = 2.8 (0.3); bout 3: SEB = 2.0 (0.2), DEB =
      2.1 (0.4); mM). No differences were observed in the blood [HLa] response to
      repeated bouts of exercise between SEB and DEB. RPE-peripheral (legs, RPE-L) was
      higher during bout 3 compared with bout 1 (P <0.05) (bout 1: SEB = 11.8 (0.8),
      DEB = 12.3 (0.2); bout 2: SEB = 12.3 (0.5), DEB = 13.3 (0.4); bout 3: SEB = 13.5
      (0.8), DEB = 14.0 (0.7); RPE-central (chest and breathing, RPE-C) was not
      affected by repeated bouts of exercise, whereas RPE-Overall (RPE-O) was higher
      during bout 3 compared with bouts 1 and 2 (P < 0.05) (bout 1: SEB = 12.5 (0.2),
      DEB = 12.3 (0.4); bout 2: SEB = 12.8 (0.4), DEB = 12.7 (0.4); bout 3: SEB = 13.7
      (0.7), DEB = 13.2 (0.3)). No interaction for RPE x condition was observed. HR
      increased with repeated bouts of exercise with HR during exercise bout 3 being
      higher than HR during exercise bout 1 (164 vs. 156 bpm, P < 0.05). There was also
      a strong trend for HR during exercise bout 3 to be higher than HR during exercise
      bout 2 (P < 0.06). A trend for a reduction in VO2 with repeated exercise was
      observed (P < 0.07), with the reduction apparently related to the SEB condition
      (P < 0.12 for VO2 x condition). PO and kcal.min-1 were not affected by repeated
      bouts of exercise. RER decreased significantly with each repeated bout of
      exercise (from RER = 0.96 to RER = 0.89, P < 0.05) with no difference observed
      between SEB and DEB. CONCLUSIONS: We conclude that the blood [HLa]-RPE relation
      is altered by repeated bouts of exercise and that this alteration does not appear
      to be affected by recovery time between exercise bouts (up to 3.5 h of recovery).
      These data suggest that, after the first exercise bout, RPE should not be used to
      produce a specific blood [HLa] on subsequent exercise bouts.

PMID- 9662682
TI  - Physiological responses to simulated rock climbing at different angles.
AB  - PURPOSE: Although rock climbing has increased in popularity as a recreational
      activity and competitive sport, few studies have assessed the physiological
      demands of the activity. To describe the physiological responses to rock climbing
      at different angles. METHODS: Sixteen experienced climbers (age = 26 +/- 8 yr)
      attempted intermittent climbing bouts at different angles on a special rock
      climbing treadmill (Brewer's Ledge Treadwall). Heart rate (HR) was monitored
      continuously, and VO2 was determined at 20-s intervals during each climbing bout.
      Immediately after each bout, the subject provided a rating of perceived exertion
      (RPE), and an average of right and left handgrip force (HG) was obtained. Blood
      was collected via fingerprick after each bout and analyzed for lactate (BL). On a
      separate day, each subject completed a steady-state treadmill running bout at a
      HR equal to that obtained at an 86 degree angle during the climbing test. This
      test was followed by a progression to exhaustion to determine peak HR and VO2
      responses. RESULTS: While HR increased with climbing angle, VO2 did not
      significantly vary. BL began to significantly increase as the angle exceeded
      vertical (91 degrees) and continued to increase with successive angles. HG
      decreased with increasing angle and was negatively correlated with BL (r = 
      0.96). Scores for RPE increased with steeper angles. The comparison of steady
      state work at the same HR for climbing versus treadmill running revealed a higher
      VO2 during running with no differences in BL and RPE. CONCLUSIONS: Based upon
      these results, it was concluded that continuous rock climbing over terrain
      steepness of 80 degrees to 102 degrees presents a "very heavy" work challenge,
      averaging 8.4-9.0 metabolic equivalents, regardless of angle. Despite similar RPE
      and BL, the relative exercise intensity elicited from simulated rock climbing is
      lower than that of running at the same HR.

PMID- 9662683
TI  - Creatine supplementation in endurance sports.
AB  - PURPOSE: Creatine is a physiologically active substance indispensable to muscle
      contraction. The increase in creatine phosphate obtained by supplementation is
      greater than the increase in total creatine achieved by specific sports training.
      Less well-trained people can produce an immediate energy store when supplementing
      creatine such as is otherwise achieved by top athletes on normal nutrition by
      means of speed and power training. The publications so far available indicate
      that creatine accumulation in muscle was accomplished using relatively high doses
      (20 g daily over 5 d). The objective of our study was to investigate the
      alterations in creatine and creatinine concentrations following lower dosages.
      METHODS: As intermediate and finishing spurts under anaerobic conditions are
      gaining in importance in endurance sports, we created a special exercise test for
      triathletes combining endurance and interval performance. After a pretreatment
      exercise test was performed, the athletes ingested 6 g of creatine daily, divided
      into two portions for 5 d. On day 6, another exercise test was performed.
      RESULTS: Creatine supplementation was found to have no influence on the
      cardiovascular system, oxygen uptake, and blood lactate concentration. The fall
      in blood glucose during the exercise test was significantly reduced after
      consumption of creatine. Although interval power performance was significantly
      increased by 18%, endurance performance was not influenced. CONCLUSIONS: We
      conclude that creatine supplementation at doses of 6 g daily has positive effects
      on short-term exercise included into aerobic endurance exercise.

PMID- 9662684
TI  - Fitness and energy expenditure after strength training in obese prepubertal
      girls.
AB  - PURPOSE: The purpose of this study was to determine the effects of a school
      based, low-volume strength training program on energy expenditure, strength, and
      physical fitness in obese prepubertal girls. METHODS: A longitudinal, 5-month
      strength training exercise program was undertaken by healthy, obese (> 95th
      percentile weight-for-height, N = 11) girls age 7-10 yr. The following were
      measured: strength by the one-repetition maximum test; fitness (VO2peak) by a
      treadmill exercise test; resting metabolic rate (RMR), 24-h sedentary energy
      expenditure (SEE), and sleeping metabolic rate (SMR) by room respiration
      calorimetry; and total energy expenditure (TEE) by the doubly labeled water
      method. Physical activity energy expenditure (AEE) was calculated as TEE-(RMR +
      0.1.TEE) and physical activity level (PAL) as TEE/RMR. An age-matched,
      nonoverweight control group was measured for (VO2peak) and RMR over the same time
      period. RESULTS: Strength increased by 19.6 and 20.0% in the upper and lower body
      (P < 0.01), respectively. (VO2peak) (mL.min-1) increased in both groups over time
      (P < 0.05), but not when covaried for fat-free mass (FFM) or weight. After
      adjusting for FFM or weight, RMR did not change, but SMR and 24-h SEE decreased
      significantly in the exercise group. There were no changes in nonprotein
      respiratory quotient or substrate oxidation. No changes in TEE, AEE, and PAL
      occurred, either unadjusted or adjusted for FFM or weight. CONCLUSION: This long
      term, school-based, low-volume strength training program favorably increases
      strength in obese prepubertal girls but does not increase their daily energy
      expenditure.

PMID- 9662685
TI  - Training and overtraining: an introduction.
AB  - Elite sport requires high training volumes. However, little is known about the
      relationship between training volume and performance development. This
      relationship appears to have an inverted U-shape. Short-term overtraining or
      overreaching is probably associated with insufficient metabolic recovery,
      resulting in a decline in ATP levels. Systemic overtraining or staleness is
      attributed to failure of the hypothalamus to cope with the total amount of
      stress. Clinically, a parasympathetic and sympathetic form has been
      distinguished. It is assumed that these two forms express different stages of
      staleness. No specific, simple, and reliable parameters are known to diagnose
      overreaching and overtraining in the earliest stage.

PMID- 9662686
TI  - Autonomic imbalance hypothesis and overtraining syndrome.
AB  - PURPOSE: The parasympathetic, Addison type, overtraining syndrome represents the
      dominant modern type of this syndrome. Beside additional mechanisms, an autonomic
      or neuroendocrine imbalance is hypothesized as underlying. METHODS/RESULTS:
      Several findings support this thesis. During heavy endurance training or
      overreaching periods, the majority of findings give evidence of a reduced adrenal
      responsiveness to ACTH. This is compensated by an increased pituitary ACTH
      release. In an early stage of the overtraining syndrome, despite increased
      pituitary ACTH release, the decreased adrenal responsiveness is no longer
      compensated. The cortisol response decreases. In an advanced stage of
      overtraining syndrome, the pituitary ACTH release also decreases. In this stage,
      there is additionally evidence for decreased intrinsic sympathetic activity and
      sensitivity of target organs to catecholamines. This is indicated by decreased
      catecholamine excretion during night rest, decreased beta-adrenoreceptor density,
      decreased beta-adrenoreceptor-mediated responses, and increased resting plasma
      norepinephrine levels and responses to exercise. However, this complete pattern
      is only observed subsequent to high-volume endurance overtraining at high caloric
      demands. CONCLUSION: The described functional alterations of pituitary-adrenal
      axis and sympathetic system can explain persistent performance incompetence in
      affected athletes.

PMID- 9662687
TI  - Overtraining and glycogen depletion hypothesis.
AB  - Low muscle glycogen levels due to consecutive days of extensive exercise have
      been shown to cause fatigue and thus decrements in performance. Low muscle
      glycogen levels could also lead to oxidation of the branched chain amino acids
      and central fatigue. Therefore, the questions become, can low muscle glycogen not
      only lead to peripheral and central fatigue but also to overtraining, and if so
      can overtraining be avoided by consuming sufficient quantities of carbohydrates?
      Research on swimmers has shown that those who were nonresponsive to an increase
      in their training load had low levels of muscle glycogen and consumed
      insufficient energy and carbohydrates. However, cyclists who increased their
      training load for 2 wk but also increased carbohydrate intake to maintain muscle
      glycogen levels still met the criteria of over-reaching (short-term overtraining)
      and might have met the criteria for overtraining had the subjects been followed
      for a longer period of time. Thus, some other mechanism than reduced muscle
      glycogen levels must be responsible for the development and occurrence of
      overtraining.

PMID- 9662688
TI  - Overtraining and immune system: a prospective longitudinal study in endurance
      athletes.
AB  - A prospective longitudinal study investigated for 19 +/- 3) months whether
      immunophenotypes of peripheral leukocytes were altered in periods of severe
      training. Leukocyte membrane antigens (CD3, CD4, CD8, CD14, CD16, CD19, CD45,
      CD45RO, and CD56) of endurance athletes were immunophenotyped (dual-color flow
      cytometry) and list mode data analyzed by a self-learning classification system
      in a state of an overtraining syndrome (OT; N = 15) and several occasions without
      symptoms of staleness (NS; N = 70). Neither at physical rest nor after a short
      term highly intensive cycle ergometer exercise session at 110% of the individual
      anaerobic threshold did cell counts of neutrophils, T, B, and natural killer
      cells differ between OT and NS. Eosinophils were lower during OT, activated T
      cells (CD3+HLA/DR+) showed slight increases (NS: 5.5 +/- 2.7; OT 7.3 +/- 2.4%
      CD3+ of cells; means +/- SD; P < 0.01) during OT without reaching pathological
      ranges. The cell-surface expression of CD45RO (P < 0.001) on T cells, but not
      cell concentrations of CD45RO+ T cells, were higher during OT. OT could be
      classified with high specificities (92%) and sensitivities (93%). It is concluded
      that OT does not lead to clinically relevant alterations of immunophenotypes in
      peripheral blood and especially that an immunosuppressive effect cannot be
      detected. Immunophenotyping may provide help with the diagnosis of OT in future,
      but the diagnostic approach presented here requires improvements before use in
      sports medicine practice is enabled.

PMID- 9662689
TI  - Training of rowers before world championships.
AB  - In rowing, static and dynamic work of approximately 70% of the body's muscle mass
      is involved for 5.5 to 8 min at an average power of 450 to 550 W. In high load
      training phases before World Championships, training volume reaches 190 min.d-1,
      of which between 55 and 65% is performed as rowing, and the rest is nonspecific
      training like gymnastics and stretching and semispecific training like power
      training. Rowing training is mainly performed as endurance training, rowing 120
      to 150 km or 12 h.wk-1. Rowing at higher intensities is performed between 4 and
      10% of the total rowed time. The increase in training volume during the last
      years of about 20% was mainly reached by increasing nonspecific and semispecific
      training. The critical borderline to long-term overtraining in adapted athletes
      seems to be 2 to 3 wk of intensified prolonged training of about 3 h.d-1.
      Sufficient regeneration is required to avoid overtraining syndrome. The training
      principles of cross training, alternating hard and easy training days, and rest
      days reduce the risk of an overtraining syndrome in rowers.

PMID- 9662690
TI  - Monitoring training in athletes with reference to overtraining syndrome.
AB  - PURPOSE: Overtraining is primarily related to sustained high load training, often
      coupled with other stressors. Studies in animal models have suggested that
      unremittingly heavy training (monotonous training) may increase the likelihood of
      developing overtraining syndrome. The purpose of this study was to extend our
      preliminary observations by relating the incidence of illnesses and minor
      injuries to various indices of training. METHODS: We report observations of the
      relationship of banal illnesses (a frequently cited marker of overtraining
      syndrome) to training load and training monotony in experienced athletes (N =
      25). Athletes recorded their training using a method that integrates the exercise
      session RPE and the duration of the training session. Illnesses were noted and
      correlated with indices of training load (rolling 6 wk average), monotony (daily
      mean/standard deviation), and strain (load x monotony). RESULTS: It was observed
      that a high percentage of illnesses could be accounted for when individual
      athletes exceeded individually identifiable training thresholds, mostly related
      to the strain of training. CONCLUSIONS: These suggest that simple methods of
      monitoring the characteristics of training may allow the athlete to achieve the
      goals of training while minimizing undesired training outcomes.

PMID- 9662691
TI  - Respiratory muscle fitness and exercise endurance in healthy humans.
AB  - New evidence exists that the respiratory muscles may limit exercise performance
      in healthy humans. Four weeks of isolated respiratory training (30 min
      normocapnic hyperpnea, 5 d.wk-1 significantly increased the endurance time of
      respiratory muscles and the endurance time of constant-load bicycle tests in
      sedentary as well as physically active subjects once respiratory muscles had
      recovered from the training. Minute ventilation and blood lactate concentration
      were reduced during post-training exercise. Furthermore, respiratory trained
      subjects had lost the sensation of breathlessness. Maximal oxygen consumption was
      not affected by respiratory training. The mechanism by which respiratory training
      improves overall physical performance is as yet unknown.

PMID- 9662692
TI  - Overtraining and the BCAA hypothesis.
AB  - The purpose of this review was to give an answer to the question whether there
      are convincing data to support the hypothesis of an amino acid imbalance as one
      possible mechanism to explain overtraining syndrome. Animal studies point to an
      enhanced synthesis of the neurotransmitter 5-hydroxytryptamine through an amino
      acid imbalance at the blood-brain barrier with a preferable tryptophan uptake
      into the brain, resulting in premature fatigue. Human studies, however, show
      contradictory results, mainly because of nonstandardized methodology, so that a
      final conclusion cannot be made at present. BCAA supplementation in addition to
      standard carbohydrate ingestion during sustained exercise seems to be of no
      eminent advantage to delay fatigue. The overall results concerning the BCAA
      hypothesis to explain overtraining are inconclusive and require more controlled
      experimental research.

PMID- 9662693
TI  - Respiratory sinus arrhythmia and cardiovascular neural regulation in athletes.

PMID- 9662694
TI  - [Metastable phenotype of bacteria].
AB  - This review analyzes data available in the literature and the author's own data
      on the phenotypic variability of bacteria that occurs within the framework of a
      genotype unchanging in terms of the genetic information stored. This variability
      is a form of bacterial adaptation to an unstable environment and results from a
      specific form of natural selection. This phenomenon arose evolutionarily not as a
      mechanism to provide genetic diversity for the divergence process but as a
      mechanism of species stabilization; therefore, it was termed phenotype
      metastability. It includes, as specific variants, processes known as phase and
      antigenic variations, R-S-M dissociation, phenotype conversion, etc. The
      mechanisms of phenotype metastability are extremely diverse. They include
      alternative expression (of the switch on-switch off type) of individual genes or
      small groups of genes; variation in the composition of synthesized proteins
      controlled at the level of transcription; expression of complex phenotypes
      adapted to different environmental conditions that involves phage transposition,
      reading-frame-shift mutations, etc. The phenomenon of phenotype metastability is
      widespread among bacteria.

PMID- 9662695
TI  - [Effect of Bacillus intermedius RNAases with various catalytic activity on
      multiplication of Escherichia coli and Bacillus subtilis].
AB  - The effect of the Bacillus intermedius ribonuclease and its mutant forms derived
      by site-specific mutagenesis on the growth of gram-positive and gram-negative
      bacteria was studied. Both catalytically active and catalytically inactive
      (mutant) ribonucleases stimulated bacterial growth, the extent of stimulation
      correlating with the catalytic activity of the enzymes. It was suggested that the
      biological activity of exogenous ribonucleases is mainly due to their catalytic
      activity.

PMID- 9662696
TI  - [Change in regulation of catabolite-dependent lux-operon, cloned in a recombinant
      plasmid, under the effect of environmental factors].
AB  - Expression of the lux-genes cloned on the recombinant plasmid pPHL7 (AprLux+) in
      Escherichia coli z905 cells was studied in various environments, including model
      aquatic ecosystems. Expression of the lux-genes strongly depended on the
      nutritional status of the medium. In particular, the cultivation of cells in
      nutrient-rich medium favored the maintenance of the initial level of expression
      of the lux-operon, whereas nutrient limitation induced recombinant cell variants
      with an impaired control of the catabolite-dependent lux-operon. On the other
      hand, long-term laboratory cultivation of recombinant strain in nutrient
      deficient media or its long-term life in model aquatic ecosystems led to the
      accumulation of cells with a stringent control on the cloned lux-genes in the
      bacterial population. The presence of the selective factor (ampicillin) in the
      medium had no significant effect on the expression of the lux-operon.

PMID- 9662697
TI  - [Change in inorganic polyphosphate chain length depending on the stage of
      Saccharomyces cerevisiae growth].
AB  - The dynamics of the content and the degree of polymerization of polyphosphates
      (PPs) during the growth of Saccharomyces cerevisiae VKM Y-1176 was studied by
      chemical methods and P NMR spectroscopy. The overall PP content of Saccharomyces
      cerevisiae cells growing in orthophosphate-sufficient medium was found to
      increase until glucose was exhausted in the medium. In the early logarithimic
      phase, the degree of polymerization of PPs (high-polymeric PPs in particular)
      fell drastically. Further cultivation of yeast in the glucose-depleted medium led
      to a decrease in the cellular content of all PP fractions without any
      considerable shortening of their chain length; by the 24th h, high-polymeric PPs
      accumulated in the cells. Shortening of PPs against a background of their intense
      synthesis in yeast cells growing in glucose-and orthophosphate-sufficient medium
      can be explained by the involvement of so far unknown mechanisms of activation of
      polyphosphate-depolymerizing enzymes.

PMID- 9662698
TI  - [Micromycetes extracellular proteinases with fibrinolytic and anticoagulant
      properties].
AB  - One hundred and sixteen strains of microscopic fungal belonging to different
      taxonomic groups were tested for their ability ti synthesize extracellular
      proteinases with caseinolytic, fibrinolytic, plasminogen activator-like, and
      anticoagulant (prolonging the partial thromboplastin time) activities. Several
      producers of anticoagulants prolonging the partial thromboplastin time, probably
      via the activation of the protein C system, were revealed. The effectiveness of
      the fungal anticoagulants was close to that of the protein C activators from
      Agkistrodon snake venom.

PMID- 9662699
TI  - [Mycocinogeny in Bullera genus: killer activity of Bullera unica and intragenus
      killer-sensitive relationships].
AB  - The killer toxin secreted by the type strain of Bullera unica is sensitive to
      proteases and high temperature and displays fungicidal activities in a pH range
      of 3.5-6. Ascomycetous yeasts are resistant to this toxin except for
      Lipomycetaceae and two species of debaryomycetes. This mycocin displays activity
      against basidiomycetous yeasts, primarily those of tremellaceous affinity. The
      killer phenotype of B. unica is retained after treatment with agents eliminating
      extrachromosomal genetic elements. Intrageneric killer-sensitive relationships
      among within the genus Bullera were studied using all known in this genus; the
      results are discussed in taxonomic terms.

PMID- 9662700
TI  - [Ecological consequences of radioactive pollution for soil bacteria within the 10
      km region around the Chernobyl Atomic Energy Station].
AB  - The diversity of aerobic chemoorganotrophic (capable of growing on nutrient agar)
      bacteria in radioactive soil (0.3-17.0 microCi/kg soil) sampled in the 10-km zone
      around the Chernobyl Nuclear Power Plant (CNPP) was found to be lower than that
      observed in control, uncontaminated soil with a radioactivity of 0.002-0.006
      microCi/kg soil. All the radioactive soil samples contained the bacteria Bacillus
      cereus and Methylobacterium extorquens or M. mesophillicum, which exhibited a
      high tolerance to 0.3-1.0 M hydrogen peroxide, whose action can to a certain
      extent simulate the effect of ionizing radiation. Some of the contaminated soil
      samples contained other species of chemoorganotrophic bacteria with a low
      tolerance to H2O2. The survival of bacteria in the Chernobyl accident zone is
      probably due to the functioning of mechanisms efficiently neutralizing peroxide
      compounds and repairing radiation-damaged DNA. The population of cellulolytic,
      nitrifying, and sulfate-reducing bacteria in contaminated soil was found to be 1
      2 orders of magnitude less than in control soil, indicating the unfavorable
      effect of anthropogenic radiation on the abundance and diversity of soil
      bacteria.

PMID- 9662701
TI  - [Old problems of new bacterial systematics].
AB  - This review analyzes the situation that arose after the existence of adaptive
      mutations had been proven. Manifold acceleration of the mutation process and
      intragenome rearrangements in nondividing cells demonstrates the inapplicability
      of the theory of neutral evolution to bacteria, the lack of isochronism between
      the evolution of individual macromolecules and the organism as a whole, and thus,
      the invalidity of using rRNA homologies as markers of the position of the
      organism in the phylogenetic tree and in the taxonomic system.

PMID- 9662702
TI  - CD36-dependent adhesion and knob expression of the transmission stages of
      Plasmodium falciparum is stage specific.
AB  - Plasmodium falciparum trophozoites sequester from the peripheral circulation by
      adherence to host endothelium. Gametocytes, also sequester during maturation.
      Analysis of the adhesion phenotype of stage I to V gametocytes of several
      isolates/clones was assessed by binding of infected cells to C32 melanoma cells
      (C32MC) and the purified adhesion proteins, leucocyte differentiation antigen
      (CD36) and intercellular adhesion molecule-1 (ICAM-1). These cells and proteins,
      have previously been shown to be receptors for adherence of trophozoites. Early
      gametocytes (stages I-IIA) were found to bind to C32MC as well as the purified
      receptor CD36 but not to ICAM-1. Early gametocytes bound to C32MC via CD36 and
      the parasite ligand involved in this binding was trypsin sensitive. Stage IIB to
      V gametocytes did not adhere to C32MC, CD36 nor ICAM-1. Electron-dense
      protruberances known as knobs and histidine rich protein 1 (HRP 1) expression
      have been associated with trophozite adhesion to CD36. Knobs were present at the
      surface of early but not late gametocyte infected cells. Stage-specific patterns
      of HRP 1 expression, consistent with a role for this molecule in CD36 adhesion of
      early gametocytes, were also observed. The adhesion phenotype of these young
      gametocytes was indistinguishable from that of the trophozoites by all criteria
      examined. These data support the hypothesis that other host receptors mediate the
      binding of late gametocytes.

PMID- 9662703
TI  - Biophysical model for organic acid excretion in Ascaris suum.
AB  - To develop a model for the mechanisms of organic acid excretion in nematodes, we
      measured the concentrations of volatile fatty acids (VFAs), pH and electrical
      potentials across hypodermal and muscle membranes and across the composite body
      wall (consisting of hypodermis, muscle and cuticle) of Ascaris suum using
      standard chromatographic and microelectrode recording techniques. In incubates
      containing one parasite in 20 ml modified Ascaris Ringer's solution, the level of
      combined VFAs excreted into the medium increased linearly for about 18 h, then
      plateaued at a concentration of 4.2 mM; the medium acidified rapidly to a plateau
      at about pH 5.0 within 4-6 h. Following 24 h incubations, the concentrations of
      VFAs in the hypodermis, muscle, and pseudocoelomic compartments were 62.4 +/-
      8.1, 62.3 +/- 7.8 and 74.4 +/- 3.2 mM, respectively. The pseudocoelomic fluid was
      more acidic (pH 6.52 +/- 0.06) than the hypodermis (pH 6.78 +/- 0.03) or muscle
      (pH 6.77 +/- 0.03). These data and the electrical potentials across hypodermal (
      57.9 +/- 6.3 mV) and muscle (-30.3 +/- 0.8 mV) membranes were used to determine
      the equilibrium concentrations for protonated (HVFA) and anionic (VFA-) forms of
      the acids across these membranes and across the cuticle. Under these conditions,
      little transmembrane or transmural excretion of HVFAs is expected to occur in A.
      suum. However, a 16-27 mV driving force for VFA- excretion exists across
      hypodermal and muscle membranes, and a larger driving force is predicted to exist
      for these anions across the cuticle. This driving force could provide potential
      energy for VFA- excretion through anion channels which exist in muscle and
      hypodermal membranes of this parasite, or for facilitated transport systems.

PMID- 9662704
TI  - Expression and regulation of mitochondrial uncoupling protein 1 from brown
      adipose tissue in Leishmania major promastigotes.
AB  - Rat uncoupling protein 1 (UCP1) was successfully translated in transfected
      Leishmania major promastigotes. Immune electron microscopy revealed that the
      protein was exclusively in the mitochondria. UCP1 expression was about 350,000
      copies per promastigote, accounting for 4.7% of the total mitochondrial protein.
      In intact parasites, expression of UCP1 induced a slight increase in respiratory
      rate and a modest decrease in mitochondrial membrane potential (delta psi(m)). In
      contrast, in digitonin-permeabilized parasites, a significantly lower value both
      in delta psi(m) (57 +/- 10 vs 153 +/- 12 mV) and respiratory control ratio (0.99
      vs 1.54) were observed for UCP1 versus control parasites, although when UCP1
      activity was inhibited by bovine serum albumin (BSA) and GDP, control values were
      restored. Therefore, a fully functional UCP1 was present and only partially
      inhibited in vivo by endogenous purine nucleotides. However, neither ATP levels,
      growth rate nor mitochondrial protein import differed significantly between both
      types of parasites. Expression of the pore-like mutant UCP1 delta 9 was
      deleterious to the organism. Consequently, Leishmania was capable of expressing
      and importing into mitochondria proteins from higher eukaryotes lacking an N
      terminal targeting pre-sequence as UCP1. As described previously, parasite
      metabolism had only a limited tolerance to mitochondrial disfunction.
      Transfection of Leishmania with foreign proteins which play an important
      regulatory role in metabolism is a useful tool to study both parasite metabolism
      in general, and alternative pathways involved in maintaining internal
      homeostasis.

PMID- 9662705
TI  - Molecular characterization of susceptible and naturally resistant strains of
      Trypanosoma cruzi to benznidazole and nifurtimox.
AB  - Twenty-seven Trypanosoma cruzi strains, susceptible or naturally resistant to the
      nitroderivatives benznidazole and nifurtimox, were analyzed using the following
      molecular markers: (i) isoenzyme patterns of six enzymes; (ii) genetic
      variability assayed by randomly amplified polymorphic DNA (RAPD) with two
      different primers; and (iii) gene probes for P-glycoprotein (TcPGP), hypoxanthine
      guanine phosphoribosyltransferase (HGPRT), the ribosomal RNA gene (rDNA) and the
      mini-exon gene (MEX), RAPD and isoenzyme profiles divided the T. cruzi strains
      into three groups, whereas the gene probes divided the T. cruzi strains in two
      groups. Strains classified as group I or II by RAPD or zymodemes Z1 or Z2 by
      isoenzyme analysis were either susceptible or naturally resistant to the
      nitroderivatives. In contrast, strains classified as group III by RAPD and
      zymodeme ZB by isoenzyme analysis were only drug susceptible and showed
      polymorphisms for HGPRT and TcPGP. No correlation was observed between drug
      susceptibility and polymorphisms of rDNA and MEX. Eighteen T. cruzi strains
      isolated from different geographic regions were included in this study. Thus,
      from a total of 45 T. cruzi strains analyzed, all 19 of zymodeme B were
      susceptible to the experimental treatment independent of their geographic origin.

PMID- 9662706
TI  - Structure, sequence, and transcriptional analysis of the Babesia bovis rap-1
      multigene locus.
AB  - The complexity of multigene families encoding rhoptry proteins and the generation
      of new variants in these families are constraints to development of vaccines
      incorporating rhoptry proteins. For example, the Babesia bigemina rhoptry
      associated protein (rap)-1 locus is composed of tandemly arranged genes including
      four polymorphic rap-1a genes and two classes of divergent genes, rap-1b and rap
      1c. B. bigemina rap-1 polymorphism reflects recombination and gene conversion and
      results in multiple RAP-1 proteins with unique B- and T-cell epitopes. Is this
      complex locus structure and recombination a required feature of the rap-1 gene
      family among Babesia species? We addressed this question by analysis of the rap-1
      locus in B. bovis. Sequence analysis of an 11 kb genomic clone representing the
      B. burn rap-1 locus revealed only two identical and continuous rap-1a gene
      copies, rap 1a-1 and rap-1a-2, located in a similar head to tail orientation.
      Using the conserved ig gene as a marker for the 3' boundary of the rap-1 locus,
      we conclude that divergent rap-1b and rap-1c genes, present in B. bigemina, are
      not similarly cis-linked to the B. bovis rap-1 locus. Analysis of the rap-1a
      genes 1 and 2 from each of multiple B. bovis strains from North and South America
      demonstrated RAP-1 size conservation with very limited amino acid sequence
      variation. The results suggest that the simple two gene arrangement in the B.
      bovis rap-1 gene family was generated by gene duplication and, in contrast to the
      B. bigemina rap-1 locus, both genes evolved together using homogenization
      mechanisms with point mutation as the single mechanism for gene variation. Three
      discontinuous non-rap-1 genes are closely cis-linked to the B. bovis rap-1 locus
      and the presence of multiple introns in these genes may limit rap-1 gene
      variation due to unequal crossing over. The different mechanisms likely involved
      in the evolution of the rap-1 family in B. bigemina versus B. bovis are reflected
      in the marked structural and antigenic polymorphism in the B. bigemina RAP-1
      molecules as compared with the essentially monomorphic RAP-1 in B. bovis.

PMID- 9662707
TI  - Demonstration of mRNA editing and localization of guide RNA genes in kinetoplast
      mitochondria of the plant trypanosomatid Phytomonas serpens.
AB  - Maxicircle molecules of kDNA in several isolates of Phytomonas were detected by
      hybridization with the 12S rRNA gene probe from Leishmania tarentolae. The
      estimated size of maxicircles is isolate-specific and varies from 27 to 36 kb.
      Fully edited and polyadenylated mRNA for kinetoplast-encoded ribosomal protein
      S12 (RPS12) was found in the steady-state kinetoplast RNA isolated from
      Phytomonas serpens strain 1G. Two minicircles (1.45 kb) from this strain were
      also sequenced. Each minicircle contains two 120 bp conserved regions positioned
      180 degrees apart, a region enriched with G and T bases and a variable region.
      One minicircle encodes a gRNA for the first block of editing of RPSl2 mRNA, and
      the other encodes a gRNA with unknown function. A gRNA gene for the second block
      of RPSl2 was found on a minicircle sequenced previously. On each minicircle, a
      gRNA gene is located in the variable region in a similar position and orientation
      with respect to the conserved regions.

PMID- 9662708
TI  - Molecular characterization of a fucosyltransferase encoded by Schistosoma
      mansoni.
AB  - The glycans of schistosomes include many complex carbohydrates that contain
      fucose. Although the biological functions of these complex carbohydrates are not
      yet clearly understood, some of these structures are thought to play essential
      roles in the life cycle of the parasite. Here we present the molecular cloning
      and characterization of a fucosyltransferase of Schistosoma mansoni with a DNA
      sequence similarity of 84.6 and 63.7% to mouse and human fucosyltransferase type
      VII. Southern blot analysis of genomic DNA indicated that this S. mansoni
      fucosyltransferase is the product of a single gene. The schistosome cDNA sequence
      that we obtained contains an open reading frame encoding a protein of 351 amino
      acids with a predicted molecular size of 40.5 kDa. From the amino acid sequence,
      we predicted two potential N-linked and one O-linked glycosylation site. Western
      blot studies of extracts from stably transfected CHO cells showed a band
      corresponding to the schistosome fucosyltransferase at 50 kDa, suggesting that
      the enzyme is indeed glycosylated. We further demonstrated the expression and
      enzymatic activity of the fucosyltransferase in the transfected cells by
      immunofluorescence studies and flow microfluorimetric analysis, which indicated
      that the enzyme is capable of synthesizing the SLeX blood group determinant but
      not the LeX determinant in CHO cells. The identification of a fucosyltransferase
      type VII in schistosomes further underscores the importance of fucose-containing
      glycans in schistosome glycobiology.

PMID- 9662709
TI  - Mild acid stress as a differentiation trigger in Trypanosoma brucei.
AB  - In vitro differentiation of Trypanosoma brucei from the bloodstream to the
      procyclic form is efficiently induced by the combination of cold shock from 37 to
      27 degrees C and the addition of citrate/cis-aconitate (CCA) to the incubation
      medium. Here it is reported that exposure of pleomorphic bloodstream trypanosomes
      to mild acidic conditions (pH 5.5 for 2 h at 37 degrees C) not only accelerated
      the process of morphological transformation from long slender and intermediate to
      short stumpy bloodstream forms but also allowed their subsequent differentiation
      into procyclic forms even in the absence of CCA. This process appeared to involve
      the glycosylphosphatidylinositol-specific phospholipase C (GPI-PLC), since null
      GPI-PLC mutants (PLC-) appeared to be largely refractory to acid stress-induced
      differentiation. However, an effective response was restored upon reintegration
      of the GPI-PLC gene in the genome (PLC+).

PMID- 9662710
TI  - The role of cAMP in the actions of the peptide AF3 in the parasitic nematodes
      Ascaris suum and Ascaridia galli.
AB  - AF3 (AVPGVLRFamide) is an endogenous RFamide-like peptide isolated from the
      parasitic nematode Ascaris suum. It has a potent and long lasting excitatory
      effect in A. suum and Ascaridia galli. This is mediated by a mechanism
      independent of the nicotinic-like acetylcholine (ACh) receptor, which mediates
      excitatory transmission at the neuromuscular junction of both nematodes. In
      addition, AF3 has been found to sensitise A. suum muscle to the contractile
      effect of ACh. In this study, the involvement of the second messenger cAMP in
      mediating the action of AF3 on the somatic musculature of A. suum and A. galli
      has been investigated. Two approaches have been used; the effects of drugs which
      raise intracellular cAMP levels on the contractile responses to AF3 have been
      examined and biochemical assays have been used to measure the effects of AF3 on
      cAMP levels. AF3 contractions were inhibited in A. suum by 10 microM forskolin
      (by 22% of control; P < 0.05; n = 9) and by 500 microM isobutylmethylxanthine
      (IBMX, by 27% of control; P < 0.001; n = 6). AF3 decreased cAMP concentrations in
      A. suum somatic muscle (basal, 1721 +/- 134 pmol mg-1 protein; with 1 microM AF3,
      1148 +/- 133 pmol mg-1 protein; P < 0.05, n = 5). AF3 (1 microM) also reduced the
      10 microM forskolin induced potentiation of cAMP concentrations in A. suum
      (forskolin 3242 +/- 471 pmol mg-1 protein; forskolin and AF3, 1524 +/- 143 pmol
      mg-1 protein; P < 0.001, n = 6) and A. galli (forskolin 291 +/- 32 pmol mg-1
      protein, forskolin +AF3, 185 +/- 12 pmol mg-1 protein; P < 0.005, n = 5). These
      data suggest that in both nematodes the contractile effect of AF3 is, at least in
      part, regulated by cAMP.

PMID- 9662711
TI  - Cloning and in vitro expression of TPK3, a Toxoplasma gondii homologue of
      shaggy/glycogen synthase kinase-3 kinases.
AB  - As an initial effort to dissect the signaling pathways responsible for
      pathogenesis of Toxoplasma gondii infection, we report the cloning and in vitro
      functional studies of TPK3 (Toxoplasma protein kinase-3), a homologue of
      shaggy/glycogen synthase kinase-3 (GSK-3) kinases. The shaggy/GSK-3 family of
      kinases are highly conserved protein kinases that play important roles in cell
      fate determination, nuclear signaling and hormonal regulation. The TPK3 gene was
      isolated by RT-PCR with degenerate primers corresponding to highly conserved
      regions of serine/threonine protein kinases. The complete sequences of genomic
      and cDNA clones indicated the open reading frame, 1185 bp in size, is interrupted
      by five introns. The predicted protein sequence of TPK3 shows 54% identity to
      shaggy/GSK-3 over the catalytic domains. Southern analysis revealed TPK3 is a
      single copy locus in the Toxoplasma genome. Antisera to other GSK-3 proteins from
      other species recognized GST-TPK3 and a protein of the predicted size in
      parasites lysates. In vitro kinase assays with GST-TPK3 indicated that TPK3
      autophosphorylates and phosphorylates protein phosphatase inhibitor-2 (I-2), a
      specific substrate of GSK-3 kinase.

PMID- 9662712
TI  - Gene synteny in species of Plasmodium.
AB  - We have attempted to establish the degree of linkage conservation between
      different species of the malaria parasite Plasmodium. Initially, the chromosome
      locations of 42 homologous genes were established in parasites from a rodent
      malaria species and the human malaria parasite P. falciparum. Of these genes, 26
      appeared to be conserved within ten synteny groups between the two genomes.
      Several synteny groups were analysed further by long-range restriction mapping of
      digested chromosomes. Finally, a fine restriction map of one of the linkage
      groups was made from the rodent malaria parasites P. berghei and from P.
      falciparum and from the simian malaria parasite P. knowlesi. The fine-scale
      organisation of this linkage group appears to have remained intact among the
      three species, despite the evolutionary distance between them. This provides the
      first example of linkage conservation between the rodent, simian and human
      malaria species, which represent three different branches of the inferred
      phylogenetic tree of the genus Plasmodium.

PMID- 9662713
TI  - Actin-binding proteins of invasive malaria parasites and the regulation of actin
      polymerization by a complex of 32/34-kDa proteins associated with heat shock
      protein 70kDa.
AB  - Movement of the malaria parasite into a host erythrocyte during invasion is
      thought to involve polymerization of parasite actin. We have used F-actin
      affinity chromatography to isolate actin-binding proteins from Plasmodium
      knowlesi merozoites, in an attempt to identify proteins responsible for
      regulating parasite actin polymerization during invasion. Five major proteins, of
      molecular masses 75, 70, 48, 40 and 34 kDa, were reproducibly eluted from the F
      actin columns. The 70 kDa actin-binding protein was identified by tryptic peptide
      microsequencing as heat shock protein-70 kDa (HSC70); this identification was
      confirmed by Western blotting with anti-HSC70 antibody, and binding of the
      protein to ATP-agarose. A doublet of 32/34-kDa proteins coeluted with parasite
      HSC70 from the F-actin and ATP-agarose columns; a complex of these three proteins
      was also observed by gel filtration chromatography Highly enriched fractions
      containing the Plasmodium HSC70/32/34 complex inhibited the polymerization of
      rabbit skeletal muscle actin, in vitro. This capping activity was calcium
      independent, and abrogated by phosphatidylinositol 4,5-bisphosphate. The average
      length of the actin filaments polymerized in presence of the HSC70/32/34-kDa
      complex was significantly shorter than in the absence of the complex, consistent
      with a capping activity. The capping or uncapping of actin filament ends by the
      HSC70/32/34-kDa complex during invasion could provide a mechanism for localized
      actin filament growth and movement of the parasite into the host cell.

PMID- 9662714
TI  - Molecular cloning of an enzymatically active thioredoxin peroxidase from
      Onchocerca volvulus.

PMID- 9662715
TI  - Is GnRH reduced at the midcycle surge in the human? Evidence from a GnRH
      deficient model.
AB  - Recent studies indicate that the midcycle gonadotropin surge in the human occurs
      without an increase in hypothalamic gonadotropin-releasing hormone (GnRH) pulse
      frequency. In addition, previous studies employing a GnRH antagonist to provide a
      semiquantitative estimate of endogenous GnRH secretion suggest that the overall
      amount of GnRH secreted is decreased at the time of the surge. To investigate the
      hypothesis that a normal gonadotropin surge can be generated in the human with a
      decreased amount of GnRH at the midcycle, 7 GnRH-deficient subjects underwent two
      cycles of a physiologic regimen of intravenous pulsatile GnRH therapy. In the
      control cycle, 75 ng/kg/bolus of GnRH, a dose known to be sufficient for
      folliculogenesis, was administered throughout the cycle, using physiological
      frequencies. In a second cycle, the bolus dose of GnRH was decreased by one-half
      log order to 25 ng/kg just prior to the luteinizing hormone surge and returned to
      75 ng/kg after documented ovulation. All cycles were ovulatory. The peak
      luteinizing hormone level (77.4 +/- 9.7 vs. 67.5 +/- 17.6 IU/l) did not differ
      between the control and decreased GnRH cycles. There was no difference in the
      peak serum estradiol level (475.8 +/- 144.1 vs. 493.2 +/- 93.0 pg/ml), follicular
      phase length (15.0 +/- 1.3 vs. 14.8 +/- 0.6 days), or progesterone level (22.4 +/
      5.1 vs. 34.8 +/- 5.7 ng/mg) on day 6 of the luteal phase in the control and
      decreased GnRH cycles, respectively. Three pregnancies were achieved in each of
      the control and reduced GnRH cycles. We conclude that a decreased overall amount
      of GnRH generates a normal midcycle gonadotropin surge and has no significant
      impact on luteal phase adequacy or fertility. These results provide further
      evidence that a decrease in endogenous hypothalamic GnRH secretion may occur at
      the midcycle in normal women. This study also provides evidence that the GnRH
      requirements for normal follicular and luteal phase dynamics may well be greater
      than those required for generation of a normal midcycle gonadotropin surge and
      ovulation in women.

PMID- 9662716
TI  - Evidence for GnRH regulation by leptin: leptin administration prevents reduced
      pulsatile LH secretion during fasting.
AB  - Administration of leptin during undernutrition improves reproductive function,
      but whether this occurs at the level of the brain, pituitary, or gonads is not
      yet clear. The present study tested the hypothesis that one important mechanism
      is the control of pulsatile gonadotropin-releasing hormone (GnRH) secretion. Our
      approach was to determine if leptin could prevent the marked suppression of
      pulsatile luteinizing hormone (LH) secretion which occurs during fasting. Leptin
      (3 micrograms/g i.p.; three times/48 h) or vehicle was administered during a 48
      hour fast in adult ovariectomized and estrogen-treated ovariectomized rats (n = 5
      7/group). LH was measured in blood samples collected every 6 min for 2 h before
      and after fasting. In vehicle-treated animals, plasma insulin and leptin levels
      decreased after fasting. As expected, the LH pulse frequency also decreased
      markedly. When circulating leptin remained artificially elevated during fasting,
      the suppression of LH pulse frequency did not occur. Leptin treatment maintained
      a high LH pulse frequency in the presence or absence of estrogen. The finding
      that leptin modulates LH pulse frequency indicates that this fat-derived hormone
      conveys information about nutrition to mechanisms which regulate pulsatile
      gonadotropin-releasing hormone secretion. Because this occurs in the absence of
      estrogen, the mechanism does not necessarily involve modulation of negative
      feedback.

PMID- 9662717
TI  - Characterization of the dopaminergic input to the pituitary gland throughout the
      estrous cycle of the rat.
AB  - Changes in the concentrations of dopamine (DA) and its major metabolite, 3,4
      dihydroxyphenylacetic acid (DOPAC), were characterized in the pituitary gland
      throughout the 4-day estrous cycle of the rat. Female rats were sacrificed at 2-
      to 3-hour intervals throughout each day of the 4-day estrous cycle. Pituitary
      glands were removed, and the concentrations of DA and DOPAC were determined by
      high-performance liquid chromatography coupled to electrochemical detection. The
      concentration of prolactin (PRL) in serum from these same animals was determined
      by radioimmunoassay. The concentration of DA in the anterior lobe was constant
      throughout most of the 4-day estrous cycle. Prior to initiation of the proestrous
      surge of PRL, there were significant (p < 0.05) decreases in the concentrations
      of both DA and DOPAC in the anterior lobe which returned to elevated baseline
      levels just prior to the termination of the proestrous surge of PRL. The
      concentrations of DA and DOPAC in the intermediate lobe exhibited a daily rhythm.
      However, in the intermediate as well as in the anterior lobe, there were
      significant (p < 0.001) decreases in the concentrations of both DA and DOPAC,
      coincident with the initiation of the proestrous surge of PRL. Similarly,
      coincident with the peak of the proestrous surge of PRL, there were significant
      (p < 0.001) increases in the concentrations of DA and DOPAC in the intermediate
      lobe, followed by a return to basal levels and resumption of the daily rhythm.
      The pattern of the concentrations of DA and DOPAC in the neural lobe was also
      daily in nature, with peaks occurring between 13.00 and 15.00 h each day of the 4
      day estrous cycle. These data, taken together: (1) confirm that a decrease of the
      concentrations of DA and DOPAC occurs in the anterior lobe prior to the
      proestrous surge of PRL; (2) reveal that DA is released in a daily pattern at
      intermediate and neural lobes, and (3) suggest an apparent role for DA released
      to the intermediate lobe in the regulation of the proestrous surge of PRL.

PMID- 9662718
TI  - Estrogen reduces cholecystokinin-induced c-Fos expression in the rat brain.
AB  - Recent reports have shown that estradiol increases the hypophagic effect of
      exogenous cholecystokinin-octapeptide (CCK). CCK is known to increase the
      expression of Fos, a marker of neuronal activation, in specific medullary and
      hypothalamic nuclei. The present experiment tested the hypothesis that as
      estradiol enhances that behavioral effects of CCK, there is a parallel
      amplification of CCK-induced Fos expression. Instead, estradiol pretreatment
      reduced the level of CCK-induced Fos expression in the nucleus of the solitary
      tract (NTS) and in the medial parvocellular region of the hypothalamic
      paraventricular nucleus (PVN). The number of Fos-containing cells in the
      supraoptic nucleus and other regions of the PVN were not affected by estradiol
      pretreatment. The results are consistent with the hypothesis that the NTS and/or
      the PVN may mediate the estrogen-induced increased sensitivity to peripheral
      inhibitory signals in the control of food intake.

PMID- 9662719
TI  - Estrogen receptor expression in brainstem noradrenergic neurons of the sheep.
AB  - Noradrenergic neurons are implicated in the estrogen-dependent neural regulation
      of luteinizing hormone secretion in a variety of mammalian species. The current
      study has used immunocytochemical methods to determine whether estrogen receptors
      (ER) are expressed within the brainstem of the ewe and to establish their
      relationship to noradrenergic neurons. Using a monoclonal mouse antiserum
      directed against the N-terminal of ERa, four distinct populations of ER alpha
      immunoreactive cells were identified in ovine medulla and pons. The largest
      population was found in the superficial laminae of the spinal nucleus of the
      trigeminal nerve, followed by the nucleus tractus solitarius, lateral area
      postrema, and ventrolateral medulla. Double-labelling immunocytochemistry using
      antisera directed against the ER alpha and dopamine-beta-hydroxylase revealed
      that noradrenergic neurons expressing ER immunoreactivity were only found in
      ventrolateral medulla (A1 cell group) and nucleus tractus solitarius (A2 cell
      group). No double-labelled cells were identified in the A5, A6, or A7
      noradrenergic cell groups. ERs were expressed with a clear rostrocaudal
      topography within the A1 and A2 populations, with 80-90% of noradrenergic neurons
      expressing ERA alpha in the caudalmost medulla as compared with less than 5%
      rostral to the obex. Our findings demonstrate that, as in the rat, the ovine A1
      and A2 neurons express ERs in a defined topographical manner, while, dissimilar
      to the rat, ER alpha is not synthesized by noradrenergic neurons in the other
      cell groups. These observations indicate that A1 and A2 noradrenergic neurons in
      the ovine brainstem are likely to be influenced by circulating estrogens and lay
      the neuroanatomical foundations for investigating the functional role of these
      cell populations within the gonadotropin-releasing hormone neuron network of the
      sheep.

PMID- 9662720
TI  - Differential sensitivity to ACTH, but not stress, in two sources of outbred
      Sprague-Dawley rats.
AB  - Adrenocorticotropic hormone (ACTH) is the major regulator of adrenocortical
      steroidogenesis in mammals. By comparing the sensitivity to ACTH of isolated
      adrenocortical cells from two sources of the same strain (Sprague-Dawley, SD) of
      outbred rats, we have identified a source of rat with low sensitivity to ACTH in
      vitro. Cells isolated from Holtzman SD rats had a high sensitivity to ACTH
      (minimal effective concentration 50 pg/ml), whereas Taconic SD rats had a low
      sensitivity (minimal effective concentration 250 pg/ml; maximal steroidogenesis <
      50% of Holtzman cells). The responsiveness to analogues of cyclic adenosine
      monophosphate and cholesterol was also significantly lower in Taconic SD rats.
      Taconic adrenals were smaller, had significantly more mitochondria per cell, but
      approximately 20% less total lipid droplet volume per cell. There was no
      difference in latency to ACTH in vitro; however, steroidogenesis plateaued in
      Taconic cells after 25 min, while Holtzman cells secreted corticosterone almost
      linearly for at least 120 min. By contrast, the cyclic adenosine monophosphate
      secretion increased at the same rate for at least 120 min in cells from both
      sources. There were no differences between cells from the two sources in
      immunoreactive steroidogenic enzyme content. In vivo, the magnitude of the ACTH
      and corticosterone responses to two types of stress were similar in both sources.
      The thymus glands of Holtzman rats were significantly larger than those of
      Taconic rats. It is concluded that: (1) reduced sensitivity to ACTH in vitro in
      Taconic SD rats results from differences in the later stages of the steroidogenic
      pathway; (2) factors in addition to ACTH are required for maximal steroidogenesis
      in Taconic SD rats: (3) a comparison of the steroidogenic pathways in adrenal
      cells from these two sources of outbred rats should be useful in further
      delineating the relative importance of putative intracellular signalling
      mechanisms involved in initiation and maintenance of steroidogenesis, and (4)
      these data suggest that different sources of the same strain of rats sufficiently
      diverge over time to become separate strains ('substrains'). Overreliance on a
      single source of laboratory rodent may obscure natural variability in endocrine
      responses to stress and provide a misleading indication of homogeneity of
      responses.

PMID- 9662721
TI  - Neurotoxic lesions induced by monosodium glutamate result in increased
      adenopituitary proopiomelanocortin gene expression and decreased corticosterone
      clearance in rats.
AB  - Hypothalamic-pituitary-adrenocortical function in rats with brain lesions induced
      by neonatal monosodium glutamate (MSG) treatment (4 mg/g, 5 administrations,
      i.p.) was evaluated in the present study. Using in situ hybridization we found
      increased proopiomelanocortin (POMC) mRNA levels in the adenopituitary and normal
      corticotropin-releasing hormone mRNA levels in the hypothalamic paraventricular
      nucleus in MSG-treated rats. The total content of pituitary adrenocorticotropin
      (ACTH) was not changed, while pituitary ACTH concentration was higher in MSG
      treated compared to control rats. The number of ACTH-immunostained cells per a
      constant area of adenohypophysial section, as measured by immunohistochemistry,
      was unchanged indicating that no significant condensation of corticotropes
      occurred. Basal plasma ACTH concentrations were not different, whereas morning
      corticosterone levels were elevated in rats with MSG treatment. While ACTH
      response to stress stimuli was similar in both groups of rats, corticosterone
      response to exogenous ACTH (500 ng/kg, i.v., Synacthen), short-lasting handling
      and immobilization was of the same magnitude but prolonged in MSG-treated rats.
      Based on the decline of [3H] corticosterone in plasma, a decreased corticosterone
      clearance rate was found in MSG-treated rats. These findings suggest that MSG
      treatment results in increased POMC gene expression per corticotrope of the
      atrophic pituitary resulting in maintenance of normal pituitary ACTH stores and
      plasma ACTH levels. Elevated basal levels of corticosterone in plasma as well as
      prolonged corticosterone responses to stimulations in rats treated with MSG seem
      to be due to a decreased clearance rate of corticosterone.

PMID- 9662722
TI  - Benzodiazepine and serotonergic modulation of antipredator and conspecific
      defense.
AB  - The mammalian defense repertory comprises an array of individual behaviors that
      are extraordinarily sensitive to relevant features of the threat stimulus and the
      situation in which it occurs. In parallel with increasing awareness of the
      specificity and complexity of defensive behaviors and of their potential
      relevance to psychopathologies (e.g. anxiety, panic, and depression) is an
      escalating use of natural threat stimuli such as attacking conspecifics or
      predators in paradigms aimed at evaluating drug effects on defense. A review of
      the literature on benzodiazepine (BZ) and serotonin (5-HT) effects on conspecific
      and antipredator defense, including defensive analgesia, indicates that both
      types of stimuli elicit a wide array of relevant defensive behaviors. These
      studies suggest specificity of drug effects on particular behaviors, rather than
      a general alteration of all aspects of defense. However, stimulus variability and
      possible confounding of effects are a considerable problem with conspecific
      defense paradigms, while antipredator paradigms utilizing human experimenters as
      the predator may be difficult to use with the domesticated laboratory animal
      subjects. In addition, sensitivity to the organization of defensive behaviors and
      to differences between species in defense patterns is necessary to adequate
      interpretation of results. Nonetheless, these paradigms have permitted major
      advancements in analysis of the behavioral defense systems and their sensitive
      use in drug studies will greatly facilitate an understanding of the physiology of
      defense.

PMID- 9662723
TI  - Amphetamine effects on striatal neurons: implications for models of dopamine
      function.
AB  - Models of dopamine function based on the bidirectional neuromodulation of
      afferents (40, 95) were tested by determining whether cortical ablation would
      affect the excitatory and inhibitory effects of amphetamine (AMPH) on striatal
      neurons in freely moving rats. By minimizing pre-and post-AMPH behavioral
      differences, behavioral clamping revealed that cortical ablation blocked the
      capacity of AMPH to produce a net excitation of striatal neurons that had shown
      AMPH-induced excitations under non-clamping conditions. Cortical ablation did not
      affect AMPH-induced neuronal inhibitions under behavioral clamping conditions.
      These results suggest that AMPH, possibly by enhancing dopaminergic
      neuromodulation, facilities or inhibits the activity of neurons that respectively
      receive substantial or little cortical input. Thus, the findings support models
      that assign dopamine the capacity to increase the gain of neuronal information
      processing. Basic research relevant to these models is reviewed and potential
      clinical implications are discussed.

PMID- 9662724
TI  - Biological bases of anxiety.
AB  - Anxiety is a complex psychological and behavioural trait, related to behavioural
      responses as different as seizures, memory, impulsivity or aggression. The
      biological bases analysed in the present article involve neurotransmitter
      systems, specific regions in the brain and genetic factors. The genetic approach
      is given special emphasis as it offers, in rodents, a promising field for
      acquiring knowledge on biological factors modulating anxiety.

PMID- 9662725
TI  - The role of corticotropin releasing factor in depressive illness: a critical
      review.
AB  - Corticotropin-releasing factor (CRF) is the principal neuropeptide involved in
      regulating the stress response. When centrally administered to animals it
      produces somatic changes analogous to those seen in both depression and anxiety.
      In humans, it is capable of reproducing the hormonal changes which are
      characteristically seen in depressed patients. A literature search using Medline,
      Embase Psychiatry, PsycLIT and BIDS from 1996-1997 revealed 25 studies that have
      examined CRF concentrations in patients with affective disorder. The methodology
      of these studies varies and they can be criticised, in particular, for failing to
      consider the stress response of the lumbar puncture. Recently, post-mortem
      immunocytochemical techniques have been employed to help clarify the nature of
      these abnormalities in depression. On balance, evidence from CSF sampling, post
      mortem findings and dynamic endocrine studies suggests that both hypothalamic and
      extra-hypothalamic concentrations of CRF are moderately elevated in a proportion
      of currently antidepressant treatment, high CRF concentrations tend to normalise.
      The causes of increased CRF output in depression are also unknown but may involve
      an integration of remote vulnerability factors and recent stressors perhaps
      mediated through impaired function of glucocorticoid receptors. Ultimately, the
      careful manipulation of CRF may hold therapeutic promise for sufferers of mood
      disorders.

PMID- 9662726
TI  - The suicide brain: a review of postmortem receptor/transporter binding studies.
AB  - The present review summarizes the last 15 years of research involving postmortem
      receptor/transporter binding studies on brains of suicide victims. It is our
      working hypothesis, on the basis of psychological, behavioral and epidemiological
      studies, that suicidal behavior is an independent unique behavioral entity with
      specific neurochemical characteristics. This review tries to test this hypothesis
      at the level of neurotransmitter receptors by using a different approach to data
      analysis. We suggest that this statistical approach, involving multivariate
      analyses, can contribute to the formulation of new hypotheses at the level of
      molecular biology and genetics. Such studies if undertaken in the future, would
      help define suicidal behavior as a psycho-neuro-pathological entity.

PMID- 9662727
TI  - The taste of sodium.
AB  - Sodium is crucial to physiological function. The responsibility for detecting it
      is assumed by the taste system, which devotes perhaps one quarter of its
      resources to the task. Sodium is transduced by passage into a subset of receptor
      cells, whose activity is relayed to the brain through a discrete gustatory
      channel. Responses in hindbrain, thalamus, and gustatory cortex identify the
      quality and concentration of sodium on the tongue. Coding of reinforcement may
      begin with the pons and ventral forebrain, particularly the lateral and medial
      hypothalamic nuclei. When body stores are sufficient, behavioral preference for
      sodium is mild, encompassing low concentrations and marked by weak avidity. This
      languid response disappears during sodium shortages. Avidity increases, and
      hypertonic concentrations are most preferred. This behavioral change may result
      from altered responsiveness in sodium-specific neurons that offer the sodium
      signal access to mechanisms of reinforcement. Thus, the taste system detects and
      recognizes sodium, and accords it a reward value commensurate with the needs of
      the animal.

PMID- 9662728
TI  - Perinatal costs of assisted reproductive technology.

PMID- 9662729
TI  - The role of ultrasound in the detection of endometrial pathologies in
      asymptomatic postmenopausal breast cancer patients with tamoxifen treatment.
AB  - Transvaginal ultrasonography is an effective diagnostic procedure, and thus, it
      can reasonably be used to determine which asymptomatic, postmenopausal breast
      cancer patient with tamoxifen treatment will require endometrial sampling.
      Overall, it seems that the contribution of pulsed Doppler flow in the diagnosis
      of endometrial pathologies in such patients is nonconclusive. It is suggested
      that sonohysterography is a useful diagnostic tool for the assessment of specific
      endometrial pathologies, especially of space-occupying lesions in the endometrial
      cavity, in such patients.

PMID- 9662730
TI  - Ovarian hyperstimulation syndrome: facts and fallacies.
AB  - Severe or critical ovarian hyperstimulation syndrome (OHSS) is a serious
      complication of ovarian hyperstimulation for assisted reproduction techniques
      (ART). The syndrome is characterized by cystic enlargement of the ovaries and
      fluid shifts from the intravascular to the third space. The morbidity in OHSS is
      mainly determined by the hemodynamic changes caused by increased capillary
      permeability. The incidence of OHSS depends on definitions, risk factors, ovarian
      stimulation protocols, luteal support and conception. Currently, research on the
      pathogenesis of OHSS is focused on increased capillary permeability. Several
      theories are reviewed. Until the pathogenesis of OHSS becomes clear, treatment is
      restricted to supportive therapy. The various proposals for management of OHSS
      are discussed and, based on the available data, directions for the management of
      various grades of OHSS are summarized. However, prevention and early recognition
      are still the most important tools to handle OHSS. A flowchart with preventive
      measures for OHSS is presented derived from the available literature.

PMID- 9662731
TI  - DDAVP use during pregnancy: an analysis of its safety for mother and child.
AB  - Synthetic 1-deamino-8-D-arginine-vasopressin (DDAVP) is used in the management of
      diabetes insipidus (DI). We conducted a systematic literature review of DDAVP use
      during pregnancy, with particular attention to its safety for both mother and
      infant. Studies were identified through Ovid MEDLINE from 1976 to July 1997 using
      the combined terms "desmopressin," "DDAVP," and "pregnancy". Review articles and
      published letters were also explored. One hundred one articles were retrieved, of
      which 20 met all the inclusion criteria. Included in the 20 articles were 53
      cases with the use of DDAVP for the management of DI. The therapeutic daily dose
      of DDAVP was approximately 29 micrograms intranasally (range 7.5-100 micrograms),
      with adequate DI control observed. Three of 14 women with sufficient information
      developed preeclampsia, a nonsignificant difference from the expected rate of 5
      percent (the Fisher exact test, 2-P = .08). The mode of delivery was defined for
      22 cases, with 16 uneventful vaginal births, and six cesarean delivery. There was
      no evidence of a drug interaction among the five women who received both DDAVP
      and intravenous oxytocin. Information was available on 49 live births born to DI
      mothers on DDAVP. The mean gestational age at delivery was 37.4 weeks (SD 1.3
      weeks), with an estimated mean birth weight of 2963.8 gm (range 2000-4420 gm).
      Forty-three offspring were reported as healthy (event rate 87.8 percent; 95
      percent CI 77.2-95.3 percent). Of the remaining six infants, one developed DI at
      18 months of age; a second was under 2500 gm at birth, but survived; the third
      developed hypotonia and failure to thrive at 21 months, two others had Down
      syndrome; and the sixth died of severe cardiac anomalies. Similar data were seen
      among the 41 infants whose mothers had used DDAVP throughout pregnancy. In
      conclusion, DDAVP use during pregnancy seems to be safe for both mother and
      child. Delivery does not seem to be augmented by its use, nor are there likely
      any associated adverse neonatal effects. A large database of DDAVP use during
      pregnancy is needed to confirm these findings.

PMID- 9662732
TI  - Alterations in zinc homeostasis in depression and antidepressant therapy.
AB  - Zinc (Zn2+) is an elementary ion which plays a fundamental role in a wide range
      of biological processes. Zinc is an essential component of various proteins and
      is an important modulator in the mammalian central nervous system (CNS). In CNS,
      zinc is found at high concentrations in hippocampal and cortical neurons. These
      neurons possess mechanisms for Zn2+ uptake and storage in synaptic terminals, and
      stimulation release Zn2+ ions along with neurotransmitters. Zn2+ modulates
      predominantly the excitatory (glutamatergic) and inhibitory (GABA ergic) amino
      acid neurotransmission pathways in CNS. Zinc deficiency impairs neuro- and
      immunoactivity of the mammalian organisms. In the present paper, alterations in
      the blood and brain zinc concentration in relation to depression and the
      mechanism of antidepressant therapy are discussed.

PMID- 9662733
TI  - Role of NMDA receptor in the effects of arginine-vasopressin on memory processes.
AB  - The mechanism of facilitatory action of vasopressin on memory processes,
      dependent probably on different neurotransmitter systems, remains unclear. We
      decided to study the interactions between arginine-vasopressin and ionotropic
      NMDA receptor. We estimated the influence of various antagonists of NMDA receptor
      on beneficial effect of arginine-vasopressin on consolidation of conditioned
      avoidance responses and on retrieval of memory in passive avoidance situation. We
      have shown that effect of vasopressin on consolidation is significantly reduced
      by noncompetitive antagonist of ion channel in the NMDA receptor--dizocilpine (MK
      801) and competitive antagonist of glycine recognization site--HA-966.
      Distinctly, effect of the peptide on retrieval is decreased by competitive
      antagonist of glutamate recognition site--AP-7, competitive antagonist of
      polyamines site-arcaine and noncompetitive antagonist--MK-801. This suggests that
      NMDA receptor may participate in the action of vasopressin on memory, but it
      plays different roles in consolidation and retrieval processes.

PMID- 9662734
TI  - Effect of bicuculline and angiotensin II fragment 3-7 on learning and memory
      processes in rats chronically treated with ethanol.
AB  - The aim of this study was to determine the possible influence of bicuculline, the
      antagonist of GABA-A receptor on behavioral activity (recall, acquisition of
      conditioned reflexes) of angiotension II fragment 3-7 (A II 3-7) in rats
      chronically treated with ethanol. Long term (9 weeks) ethanol intoxication
      profoundly impaired learning and memory processes in all testes used. The GABA-A
      receptor antagonist bicuculline (0.5 mg/kg ip) did not influence exploratory and
      motor activity in the control rats, but we observed tendency (without
      significance) to decrease the locomotor activity, in the alcohol-intoxicated
      groups of animals, when the drug was injected together with A II 3-7 (2 microgram
      icv). Bicuculline did not influence retrieval process in passive avoidance recall
      in both investigated groups, and when the drug was given together with AII 3-7
      significantly enhanced its action in the control group and in rats chronically
      treated with ethanol. Bicuculline significantly improved acquisition in the
      active avoidance test in the control and alcohol-intoxicated groups. Bicuculline
      injected together with A II 3-7 significantly decreased its action in the control
      group. Coadministration of bicuculline with A II 3-7 did not significantly change
      the activity of A II 3-7 in the acquisition of active avoidance test in the
      alcohol-intoxicated groups of rats.

PMID- 9662735
TI  - Influence of felodipine on experimental seizures and activity of different
      antiepileptic drugs in mice.
AB  - Effects of felodipine, the calcium channel blocker, on the electroshock,
      pentetrazole-, aminophylline-, and pilocarpine-induced seizures and on the
      anticonvulsant activity of different antiepileptic drugs against maximal
      electroshock were examined in mice. Felodipine increased the threshold for
      electroconvulsions. The drug exerted also a protective effect against
      pentetrazole-induced seizures, but not against aminophylline- and pilocarpine
      induced seizures. The protective efficacy of diazepam and diphenylhydantoin (but
      not phenobarbital and valproate) against electroconvulsions was significantly
      enhanced by felodipine. A pharmacokinetic interaction did not seem to be
      responsible for the interaction of felodipine with antiepileptic drugs in the
      maximal electroshock test.

PMID- 9662737
TI  - Effects of the dihydropyridine calcium antagonist nimodipine on the firing rate
      of cat visual neurons after systemic administration.
AB  - Nimodipine, a cerebrovasotropic dihydropyridine calcium antagonist, has gained
      increasing interest in geriatric research during last years and is discussed with
      regard to its possible involvement in restoration and preservation of brain
      plasticity. Single unit responses were recorded in the visual cortex of
      anaesthetized adult cats. Receptive fields (rf) were stimulated with light bars
      moving forward and backward or flashed on/off. Neuronal responses were analysed
      by means of peri-stimulus-time-histograms (PSTH). While stimulated with the
      flashing light the majority of neurons showed the same pattern of responses to
      nimodipine: PSTH peak was reduced 5 min after the injection and rose again in 30
      mins. The influence of nimodipine was more variable after stimulation with moving
      bars. 60% of neurons decreased and 40% increased their responses after the
      injection. In conclusion, the findings show that nimodipine has specific
      neurotropic effects which are independent of its vasodilatatory properties.

PMID- 9662736
TI  - Electrophysiological investigation of the effects of ambroxol on the
      transepithelial Na+ ion transport pathway in airways.
AB  - Isolated tracheal wall was studied by the Ussing method during selective
      inhibition of single, electrogenic, transepithelial ion transport pathways with
      either amiloride (for Na+) or bumetanide (for Cl-). It was shown that ambroxol
      influences the Na+ transepithelial transport pathway which is partly responsible
      for the hyperpolarization after mechanical stimulation of the mucosal surface of
      tracheal wall. Ambroxol augments the Na+ current during the presence of
      bumetanide in the experimental system, but diminishes it during the washing of
      amiloride from the measuring chamber. These bidirectional effects of ambroxol
      provide indirect evidence that the drug is a partial agonist for the memberance
      receptors which form part of the intrawall control system responsible for
      integration of airwall function with the transepithelial ion transport.

PMID- 9662738
TI  - Concentration of copper and zinc in blood of psoriatic patients treated topically
      with ointment containing 2-chloroethyl-3-chloropropyl sulfide.
AB  - Copper and zinc concentration in plasma, erythrocytes and whole blood was
      determined in a group of psoriatic patients (n = 80 ) before and after treatment
      with an ointment (in accordance with recommendations of the Helsinki Declaration)
      in which 2-chloroethyl-3-chloropropyl sulfide (CLEPS) is an active compound and
      in a comparative group (n = 99) of clinically healthy volunteers. The performed
      examinations revealed a significantly lower (by 19.1%) plasma copper
      concentration in patients before treatment in comparison with the control group.
      After treatment (CLEPS) plasma copper concentration increased significantly (p <
      0.001). In comparison with the control group, in erythrocytes of psoriatic
      patients copper concentration was higher both before and after treatment. Plasma
      zinc concentration in psoriatic patients was lower before treatment, whereas in
      erythrocytes, compared with the control group, it was higher both before and
      after treatment.

PMID- 9662739
TI  - Histaminergic and noradrenergic control of cyclic AMP formation in the pineal
      gland and cerebral cortex of three avian species: cock, duck, and goose.
AB  - The goal of the present study was to examine the effects of forskolin (FOR),
      histamine (HA), L-noradrenaline (NA), isoprenaline (ISO) and dopamine (DA) on
      cyclic AMP formation in whole pineal glands and cerebral cortical slices of cock,
      duck and goose. HA (100 muM) and FOR (10 muM) potently increased cyclic AMP
      production in the pineal glands of all studied avian species, showing a
      synergistic interaction when applied together. HA at the dose of 1 mM
      significantly stimulated adenylyl cyclase activity in the membrane preparations
      of cock pineal glands while lower concentrations were ineffective. HA markedly
      enhanced cyclic AMP formation in cerebral cortex of cock (an effect being
      potentiated for FOR), but did not affect the nucleotide production in this brain
      structure of duck and goose. DA (100 muM) had no effect, NA (100 muM) only
      moderately (5-22% increased, where ISO (10muM) significantly (by 50-90%) enhanced
      cyclic AM_ synthesis in avian cerebral cortex. Propranolol (1 muM) antagonized
      all these effects, while preincubation with yohimbine and prazosin significantly
      enhanced NA action in cortical slices of duck and goose.

PMID- 9662740
TI  - Effect of EMD 57445, the selective sigma receptor ligand, on the turnover and
      release of dopamine.
AB  - EMD 57445 (1, 3 and 10 mg/kg, po), a selective sigma receptor ligand without an
      affinity to dopamine receptors, induced potent, dose-dependent increases in the
      tissue DOPAC and HVA levels in the rat brain cortex, nucleus accumbens and
      striatum. The extracellular DOPAC and HVA levels after EMD 57445 and (3 and 10
      mg/kg, po) administrations, measured by microdialysis in the rat prefrontal
      cortex, were also increased, without significant effects on the outflow of
      dopamine.

PMID- 9662741
TI  - Behavioral activity of angiotensin II after stimulation of L-arginine/nitric
      oxide pathway in rats.
AB  - This study was conducted to determine what, if any, role L-arginine [an
      endogenous donor of nitric oxide (NO)] plays in the behavioral changes induced by
      angiotensin II (AII) in rats. The motility, stereotypy, spatial learning
      performance, learning of conditioned avoidance response and retention of passive
      avoidance behavior allowing to avoid aversive stimulation were investigated.
      Saline (0.9% NaCl), AII, L-arginine and AII combined with L-arginine were
      injected 15 min before the experiment into lateral cerebral ventricles (icv). L
      arginine significantly enhanced locomotor activity while the treatment with
      AIIplus L-arginine reduced number of bar approaches in the open field test. AII,
      L-arginine and AII combined with L-arginine (but not with D-arginine)
      significantly accelerated acquisition of conditioned avoidance responses and not
      significantly improved recall of the passive avoidance. Only L-arginine displayed
      a tendency to inhibit acquisition of spatial learning on the second day of
      investigation in the Morris water maze. AII, L-arginine and AII with L-arginine
      applied immediately before the experiment intensified stereotypy evoked by
      apomorphine at a dose of 1 mg/kg and amphetamine at a dose of 7.5 mg/kg given
      intraperitoneally. These results showed that: 1) L-arginine as a donor of NO
      might be involved in memory and learning processes, 2) overproduction of NO did
      not change behavioral effects of AII in these experiments.

PMID- 9662742
TI  - Genetic animal models of epilepsy.

PMID- 9662743
TI  - Antiepileptic drugs and methylxanthines: clinical significance.

PMID- 9662744
TI  - Immune response and epilepsy.

PMID- 9662745
TI  - Excitatory amino acid-induced seizure activity and seizure-related brain damage-
      a possible therapeutic potential of glutamate antagonists.

PMID- 9662746
TI  - Influence of immunotropic drugs on the anticonvulsive action of diazepam,
      phenobarbital, carbamazepine and valproate against maximal electroshock-induced
      convulsions in mice.

PMID- 9662747
TI  - Potential risk of seizures in asthma management--methylxanthines combined with
      antibiotics.

PMID- 9662748
TI  - Influence of aminophylline on the protective activity of carbamazepine against
      amygdala-kindled seizures in rats.

PMID- 9662749
TI  - Aminophylline and the anticonvulsive action of valproate against amygdala-kindled
      seizures in rats.

PMID- 9662750
TI  - Experimental diabetes sensitizes mice to electrical- and bicuculline-induced
      convulsions.

PMID- 9662751
TI  - Non-steroidal anti-inflammatory drugs and the protective activity of valproate
      and diphenylhydantoin against maximal electroshock-induced seizures in mice--an
      interaction.

PMID- 9662752
TI  - Dehydroepiandrosterone (DHEA) and systemic lupus erythematosus.
AB  - OBJECTIVE: This study was performed to evaluate in vivo and in vitro data on the
      effects of the adrenal steroid dehydroepiandrosterone (DHEA) with emphasis on its
      potential use in the treatment of systemic lupus erythematosus (SLE). METHODS:
      The literature dealing with DHEA was reviewed. RESULTS: Initially, research on
      DHEA focused on effects of DHEA in relation to obesity. Over the past decade,
      research stimulated by associations between the physiological decline in DHEA and
      aging, cardiovascular disease, changes in metabolism, brain function, and immune
      senescence have generated insight into the many effects that DHEA or its
      metabolites may have. In SLE a role for sex hormones in both the etiopathogenesis
      and disease activity is recognized. In SLE, as in aging, low DHEA levels are
      frequently found, especially with corticosteroid treatment. CONCLUSIONS: Research
      data in the elderly, on both hormonal and immunologic effects, suggest that DHEA
      may become an adjunctive treatment for SLE patients.

PMID- 9662753
TI  - A possible role for saliva as a diagnostic fluid in patients with chronic pain.
AB  - OBJECTIVES: The focus of this review was on proteins and peptides found in
      saliva. Of greatest interest were those neuropeptides relevant to nociception and
      to the pathogenesis of chronic pain syndromes. An additional goal was to develop
      a standardized protocol to collect saliva for laboratory assessment. METHODS:
      Data were obtained through discussion with experts at the medical schools in San
      Antonio and Heidelberg and a Medline literature search involving all relevant
      studies from 1966 to 1997. The literature search was based on the following key
      terms: saliva, serotonin, neuropeptide, substance P (SP), calcitonin gene-related
      peptide (CGRP), and nerve growth factor (NGF). RESULTS: The mean concentration of
      SP in the saliva of healthy normal controls ranged from 9.6 to 220 pg/mL.
      Generally, the concentration of SP was approximately three times higher in saliva
      than in plasma. In a number of painful conditions, particularly tension headache,
      substantial elevations of salivary SP were found. Mean values for salivary CGRP
      in healthy controls were approximately 22 pmol/L and were significantly elevated
      in patients with migraine attacks or cluster headache. There were no data to
      indicate prior quantitative determination of NGF in human saliva. CONCLUSIONS:
      After sampling and processing techniques have been standardized, measurement of
      neuropeptides in human saliva could provide a valuable tool for study of patients
      with chronic painful disorders such as rheumatoid arthritis, osteoarthritis, and
      even fibromyalgia syndrome.

PMID- 9662754
TI  - Alpha-interferon-induced arthritis: clinical presentation treatment, and
      prevention.
AB  - OBJECTIVE: The therapeutic applications of alpha-interferon (IFN) have expanded
      greatly to include chronic viral hepatitis and malignant disorders. Autoimmune
      phenomena occur frequently with IFN therapy, but arthritis is uncommon. We
      describe the clinical features and treatment of IFN-induced arthritis. METHODS: A
      patient with chronic myelogenous leukemia who developed arthritis secondary to
      IFN therapy is presented. The clinical features and treatment of this condition
      in 37 additional cases are reviewed. RESULTS: The most common clinical
      presentation was symmetric polyarthritis. This was associated with antinuclear
      antibodies in 72% of patients and rheumatoid factor in 34%. Cessation of IFN,
      with or without the addition of antiinflammatory or remittive agents, resulted in
      remission of arthritis in 89% and 71% of the cases, respectively. Restarting IFN
      therapy resulted in recurrence of arthritis in 63%. In the patient described in
      this report, recurrence of arthritis was prevented by coadministration of
      hydroxychloroquine (HCQ) and prednisone. CONCLUSION: Arthritis is an uncommon
      complication of IFN therapy; but it may lead to cessation of this treatment
      modality. In such cases, coadministration of a remittive agent such as HCQ may
      enable reinstitution of IFN therapy without recurrence of arthritis.

PMID- 9662755
TI  - Omega-3 fatty acids in rheumatoid arthritis: an overview.
AB  - OBJECTIVES: To review background, pharmacological properties, mechanisms of
      action, and published clinical experience using omega-3 fatty acids in rheumatoid
      arthritis. MATERIALS AND METHODS: English language publications were identified
      through a computerized search (using MEDLINE) between 1979 and 1995 using the
      terms "omega-3 fatty acids" and "fish oil". In addition, manual search and cross
      references were used to obtain published articles on the subject. Papers showing
      evidence of pharmacological properties and mechanisms of action were analyzed.
      For therapeutic efficacy, only randomized clinical trials are presented in this
      article. All papers were reviewed by a board certified rheumatologist with
      training in research methodology and critical appraisal skills. He was aware of
      study objectives. RESULTS: Main results are summarized in the text and presented
      in tables. Mean change from baseline is presented only for patients treated with
      omega-3 fatty acids. Omega-3 fatty acids are superior with respect to placebo in
      improving some outcome measures, and decrease the long-term requirements for
      nonsteroidal antiinflammatory drugs. Some of these effects are statistically
      significant, but their clinical significance remain to be established.
      CONCLUSIONS: Treatment with omega-3 fatty acids has been associated with
      improvement in some outcome measures in rheumatoid arthritis. Studies are needed
      to determine if they might represent an alternative to nonsteroidal
      antiinflammatory drugs in certain circumstances.

PMID- 9662756
TI  - The scarring processes in mucosal tissues after immune injury.
AB  - OBJECTIVES: An important feature of the healing processes is scar formation which
      may be necessary for organism survival. If it proceeds to the pathological state,
      it may impair normal function. The purpose of this review is to focus on some of
      the factors that may influence this process after immune injury, comparing it in
      the skin and mucosa. METHODS: A detailed literature search of peer-reviewed
      journals was conducted. Studies reported in all languages considered relevant and
      important were used, including humans, animals, and tissue culture. RESULTS:
      Analysis of the data indicate that the scarring process is mainly dependent on
      (1) the type of the lesion, (2) the cause and duration of injury, and (3) the
      tissue involved and its microenvironment. Equally important is the large spectrum
      and heterogenicity in the biological activity of fibroblasts and their role in
      scar formation. CONCLUSIONS: The process of scar formation is complex and
      multistep process and is affected and influenced by local and systemic factors.
      Although it appears irreversible, there are pharmacological agents available, and
      under investigation, that may minimize its detrimental effects.

PMID- 9662757
TI  - Rheumatoid hyperviscosity: analysis of a patient with intermediate complexes that
      block other autoantibodies and a review of the literature.
AB  - OBJECTIVES: To report a patient who rheumatoid arthritis presented with
      hyperviscosity syndrome, analyze this patient's rheumatoid factor, and review the
      previously reported patients. METHODS: Immunofluorescence for antinuclear
      antibodies, double immunodiffusion, enzyme-linked immunosorbent assay, and size
      exclusion chromatography were used before and after plasmapheresis to study the
      patient's rheumatoid hyperviscosity, and polyclonal gammopathy and references in
      identified papers was used to identify previously reported patients. RESULTS:
      Similar to several previous patients, this patient's sera contained both IgG and
      IgM rheumatoid factor and abundant intermediate complexes. Other autoantibodies,
      either from the patient or from other patients, were masked by rheumatoid factor
      or intermediate complexes from the reported patients sera. Rheumatic
      hyperviscosity is seen uncommonly, being reported in only 18 patients with
      rheumatoid arthritis and nine with other rheumatic illnesses. CONCLUSIONS: There
      are two mechanisms by which rheumatoid factor can lead to hyperviscosity, both of
      which require large amounts of rheumatoid factor. Rheumatoid hyperviscosity must
      be recognized because this life-threatening syndrome usually can be successfully
      treated with plasmapheresis acutely and immunosuppressives for long-term control.

PMID- 9662758
TI  - Factors related to degradation of articular cartilage in osteoarthritis: a
      review.
AB  - OBJECTIVES: Osteoarthritis (OA) is a common joint deterioration initiated by
      multiple factors. To better understand related factors in the development of this
      disease, we focused on the mechanical stress loaded on articular cartilage.
      MATERIALS AND METHODS: The anterior cruciate ligaments of rabbit knee joints were
      transected, and expression of protein kinase C (PKC) examined
      immunohistochemically. The PKC activator 12-o-tetradecanoyl-phorbol-13-acetate
      (TPA) was then administered intraarticularly. To determine the involvement of gas
      mediators, a cartilage defect was made on the medical femoral condyle of rabbit
      knee joints. Hydrostatic pressure was loaded on the cartilage taken from the
      surrounding defects, and levels of superoxide anion and nitric oxide (NO) were
      measured. Bovine chondrocytes were subjected to cyclic mechanical stretch using a
      Flexercell Strain Instrument. Proteoglycan synthesis and PKC activity were
      measured. Expression of matrix metalloproteinase (MMP)-3 and tissue inhibitor of
      metalloproteinase (TIMP)-1 in articular cartilages obtained from OA patients were
      examined using Northern blots. RESULTS: Chondrocytes from experimentally induced
      OA were stained positively with anti-alpha-PKC antibody. Intraarticular
      administration of TPA prevented the development of OA changes. Cyclic tensile
      stretch loaded on chondrocytes decreased proteoglycan synthesis and PKC activity.
      Thus, PKC is involved in the stress-mediated degradation of articular cartilage.
      Cartilage defects led to degradation of surrounding cartilage and to enhanced
      superoxide anion and NO synthesis. We also noted increased and decreased
      expressions of MMP-3 and TIMP-1 mRNA in human OA cartilage, respectively.
      CONCLUSION: PKC, gas mediators (superoxide anion, NO), and proteinases are all
      involved in OA.

PMID- 9662759
TI  - Assessing condom use practices. Implications for evaluating method and user
      effectiveness.
AB  - BACKGROUND: Consistent and correct condom use remains important to human
      immunodeficiency virus (HIV) prevention. Although many studies evaluate
      consistent condom use, few examine how condoms are used during intercourse.
      GOALS: Assess how user practices affect exposure to risks of pregnancy and
      infection during condom use. STUDY DESIGN: A cross-sectional survey on condom
      behaviors in the past month was conducted among 98 male students attending two
      Georgia universities. RESULTS: Altogether, 35 of 270 total condom uses (13.0%,
      95% confidence interval, 7.4-18.5) resulted in potential exposure to sexually
      transmitted disease and/or HIV infection or pregnancy. Both consistent and
      inconsistent users were similarly likely to report potential exposures during
      condom use. CONCLUSION: These findings suggest condom problems occur among both
      consistent and inconsistent users. Future studies of condom effectiveness must
      distinguish whether condoms were used both consistently and correctly.

PMID- 9662760
TI  - Risk factors for incident and recurrent condylomata acuminata among men. A
      population-based study.
AB  - BACKGROUND AND OBJECTIVES: The rapid increase in the number of physician office
      visits for condylomata acuminata and the association of human papillomavirus and
      cancer has prompted renewed interest in the epidemiology of this sexually
      transmitted disease. Few epidemiologic studies have examined what risk factors
      are associated with condylomata acuminata in men. GOAL: To determine what factors
      may predispose a man to the occurrence of condylomata acuminata. STUDY DESIGN: A
      population-based case-control study was conducted among male members of a health
      maintenance organization. Patients were men 18 years or older who were seen for
      condyloma at one of four primary care clinics of Group Health Cooperative of
      Puget Sound between April 1, 1987 and September 30, 1991. Control subjects were
      frequency matched to the patients on clinic site, race, and age. In-person
      interviews were used to ascertain exposure histories from both patients and
      control subjects. RESULTS: Recurrent condyloma was reported by about one third of
      our patients. Patients with multiple partners were strongly associated with
      developing the disease. Several factors were either more strongly or only
      associated with recurrent disease. Other behavioral measures, such as
      recreational drug use, were also related the occurrence of condyloma. CONCLUSION:
      These results confirm the sexual-transmitted mechanism of condyloma in men.
      Exposure to multiple partners was associated with elevated risk of both recurrent
      and incident disease. Other cofactors may be involved in the etiology of
      condyloma.

PMID- 9662761
TI  - Risk factors for incident and recurrent condylomata acuminata among women. A
      population-based study.
AB  - BACKGROUND: Condylomata acuminata is one of the most common sexually transmitted
      diseases (STDs) diagnosed in the United States, yet relatively little research
      has been conducted on the determinants of this disease in well-defined
      populations. GOAL: To determine the exposures that predispose a woman to the
      development of condylomata acuminata or genital warts. STUDY DESIGN: A population
      based case-control study was conducted among enrollees of Group Health
      Cooperative of Puget Sound. Patients (94 women with incident and 55 women with
      recurrent condyloma) were diagnosed between April 1, 1987 and September 30, 1991.
      Control subjects were 133 women without a history of genital warts. An in-person
      interview was conducted to collect information on subject characteristics,
      exposures, and on all episodes of genital warts. RESULTS: Women with five or more
      partners within the 5 years before reference date were over seven times more
      likely to have incident condyloma (relative risk [RR], 7.5; 95% confidence
      interval [CI], 3.1-18.1) and over 12 times more likely to have recurrent
      condyloma (RR, 12.8; 95% CI, 4.2-38.9) compared with women with only one sexual
      partner during this time period. An increased risk of incident condyloma was also
      associated with a history of any STD (RR, 2.6; 95% CI, 1.1-5.8), a history of
      oral herpes (RR, 2.2; 95% CI, 1.1-4.4), and a history of allergies (RR, 2.0 95%
      CI, 1.0-3.8). Our data did not support a strong association between risk of
      condyloma and smoking or recent use of oral contraceptives. CONCLUSION: Our
      results suggest that risk of condyloma is primarily related to sexual behavior.
      We did not observe a strong association between risk of condyloma and many of the
      exposures considered to be potential cofactors for anogenital cancers associated
      with other types of human papillomaviruses.

PMID- 9662762
TI  - A comparative study of therapeutic response of patients with clinical chancroid
      to ciprofloxacin, erythromycin, and cotrimoxazole.
AB  - BACKGROUND AND OBJECTIVES: Cotrimoxazole has traditionally been used as first
      drug for treatment of chancroid in India. With reports of increasing resistance
      to the drug, this study was conducted to compare treatment response of clinical
      chancroid between ciprofloxacin, 500 mg twice daily for 3 days, erythromycin, 500
      mg four times daily for 7 days, and double-strength cotrimoxazole (trimethoprim
      160 mg + sulfamethoxazole 800 mg), twice daily for 7 days. STUDY DESIGN: Forty
      six patients with a clinical diagnosis of chancroid were randomly divided into 3
      groups. Sixteen patients received ciprofloxacin, whereas 15 each received
      erythromycin and cotrimoxazole. Patients were seen on day 7, 14, and if needed
      day 21. Clinical response was noted in terms of cure, improvement, or failure.
      RESULTS: Excellent response was observed to both ciprofloxacin and erythromycin
      therapy with cure rates of 93.7% and 93.3%, respectively. Improvement was
      observed in 6.7% cases in both groups. There were no failures with either
      ciprofloxacin or erythromycin. Poor response to cotrimoxazole therapy was
      observed with 53.3% cure rates and a high failure rate of 46.7%. CONCLUSION:
      Ciprofloxacin and erythromycin are equally effective in chancroid. Ciprofloxacin
      is better in terms of dosage schedule, duration of treatment, and low cost.
      Cotrimoxazole should be discontinued as drug of choice because of high failure
      rates.

PMID- 9662763
TI  - Rectal microbicides for U.S. gay men. Are clinical trials needed? Are they
      feasible? HIVNET Vaccine Preparedness Study Protocol Team.
AB  - BACKGROUND AND OBJECTIVES: Incomplete condom use during anal sex persists among
      gay men; microbicides may provide additional protection. Despite the absence of
      efficacy or safety data, many gay men use sexual lubricants containing nonoxynol
      9 (N-9), a detergent-based spermicide under evaluation for efficacy as a vaginal
      microbicide. GOAL: Evaluate unprotected sex, lubricant use, and attitudes
      regarding possible participation in clinical trials of rectal microbicides among
      high-risk human immunodeficiency virus-(HIV) seronegative U.S. gay men in six
      cities. STUDY DESIGN: A total of 3,257 gay men were interviewed and responded to
      a self-administered questionnaire at enrollment into a longitudinal cohort study
      of HIV seroincidence. RESULTS: Among 2,216 men who practiced receptive anal
      intercourse in the previous 6 months, 438 (20%) reported they never used condoms.
      More than three fourths of 3,093 men who had anal sex used lubricants more than
      80% of the time. 41% of whom actively sought N-9 containing products. About two
      thirds said they were definitely or probably willing to participate in rectal
      microbicide clinical trials. CONCLUSION: Condom use is imperfect among men who
      report anal sex. N-9 lubricants are popular. Most gay men in this cohort indicate
      willingness to participate in rectal microbicide studies.

PMID- 9662764
TI  - Rates of and risk factors for trichomoniasis among pregnant inmates in New York
      City.
AB  - BACKGROUND: Trichomonas vaginalis is a common pathogen that is associated with
      adverse pregnancy outcomes and may serve as a cofactor in human immunodeficiency
      virus (HIV) transmission. GOAL: To define the epidemiology of trichomoniasis in a
      population of newly incarcerated pregnant women in New York City. STUDY DESIGN:
      Prospective study of 213 pregnant prisoners attending prenatal clinic. Patients
      participated in an interview regarding sexual and drug-related behaviors, and
      underwent direct culture for T. vaginalis in addition to routine testing for
      syphilis, gonorrhea, and chlamydia. RESULTS: The prevalence of trichomoniasis was
      46.9%. On univariate analysis, there was a significant association between
      trichomoniasis and older age, crack use, prostitution, known HIV infection, and
      positive serological test for syphilis. Multivariate analysis showed a
      significant association of trichomoniasis with crack use and positive serological
      test for syphilis. CONCLUSION: Trichomoniasis is highly prevalent in pregnant
      prisoners in New York City. The extent of disease observed may justify a formal
      program of testing and treatment and emphasizes the urgent need for harm
      reduction education and expanded HIV counseling and testing services in this high
      risk population.

PMID- 9662765
TI  - Sexually transmitted diseases in the incarcerated. An underexploited public
      health opportunity.

PMID- 9662766
TI  - Human immunodeficiency virus partner notification. Cost and effectiveness data
      from an attempted randomized controlled trial.
AB  - OBJECTIVE: Determine the cost and effectiveness of partner notification for human
      immunodeficiency virus (HIV) infection. METHODS: Persons testing HIV positive in
      three areas were randomly assigned one of four approaches to partner
      notification. Analysis plans changed because disease intervention specialists
      notified many partners from the patient referral group. We dropped the patient
      referral group and combined the others to assess the cost and effectiveness of
      provider referral. RESULTS: The 1,070 patients reported 8,633 partners. Of those
      1,035 were located via record search or in person. A previous positive test was
      reported by 248 partners. Of the 787 others, 560 were tested: 438 were HIV
      negative and 122 were newly identified as HIV positive. The intervention
      specialist's time totaled 197 minutes per index patient. The cost of the
      intervention specialist's time, travel, and overhead was $268,425: $251 per index
      patient, $427 per partner notified, or $2,200 per new HIV infection identified.
      No demographic characteristic of the index patient strongly predicted the
      likelihood of finding an infected partner. CONCLUSION: We could not compare the
      effectiveness of different partner notification approaches because of frequent
      crossover between randomized groups. The cost of partner notification can be
      compared with other approaches to acquired immunodeficiency syndrome prevention,
      but the benefits are not easily measured. We do not know the number of HIV cases
      prevented or the value of fulfilling the ethical obligation to warn partners of a
      potential threat to their health.

PMID- 9662767
TI  - Genital chlamydial disease in an urban, primarily Hispanic, family planning
      clinic.
AB  - BACKGROUND AND OBJECTIVES: Although chlamydia is a well-studied disease, little
      is known about the rates of genital chlamydial disease among female Hispanics in
      urban family planning clinics. GOALS: To determine the prevalence of women with
      chlamydia in two clinic populations during 1994. We also sought to describe
      previously identified and novel risk factors for chlamydial disease in this
      unique population. STUDY DESIGN: We conducted a retrospective case-control
      analysis in two community clinics in the Washington Heights section of New York
      City. RESULTS: In 1994, 4,190 screening tests were done for Chlamydia trachomatis
      in these clinics, and the prevalence of positive tests was 5.4% (227/4,190). The
      mean age of the women screened was 19.2 years and most were of Hispanic origin
      (76%), students (51%), and received Medicaid (61%). Risk factors found to be
      associated with C. trachomatis infection included young age; earlier age at first
      coitus; pregnancy at the time of chlamydia screening; concurrent gonorrheal
      infection; and the clinical findings of cervical abnormalities, vaginal
      discharge, and adnexal tenderness. Hormonal contraception appeared to be
      protective against chlamydial infection (odds ratio, 0.36%; confidence interval,
      0.17-0.77). CONCLUSION: Sexually transmitted diseases were common in our
      population because 5.4% of the women screened had chlamydial infection and 1.5%
      had concurrent gonorrheal infection. Our study confirmed risk factors established
      in other populations. These data support the need for enhanced screening efforts
      for chlamydia to decrease the prevalence of disease in our population.

PMID- 9662768
TI  - Reappraising the value of urine leukocyte esterase testing in the age of nucleic
      acid amplification.
AB  - BACKGROUND: The leukocyte esterase (LE) test has a limited role in determination
      of empiric therapy for male patients screened for urethritis because of its poor
      positive predictive value in low (< 5%) prevalence settings. The recent advent of
      nucleic acid amplification testing of first-void urine (FVU) has dramatically
      increased the ease with which widespread screening for Chlamydia trachomatis and
      Neisseria gonorrhoeae can be performed, but the costs of such testing may be
      prohibitive. The LE test may therefore have a role in management of urethritis
      because of its high negative predictive value. OBJECTIVES: To determine the
      sensitivity, specificity, and positive and negative predictive value of LE
      testing for the diagnosis of N. gonorrhoeae and C. trachomatis in male FVU
      specimens in a low-prevalence urban setting using a commercial polymerase chain
      reaction (PCR) as the gold standard. METHODS: Data were obtained on men
      presenting to an urban sexually transmitted disease clinic over a 16-month
      period. Patients were included if an FVU had been tested for the presence of LE
      using a rapid dipstick, read by an automated urine analyzer, and the sample
      (either an FVU or urethral swab) had then been processed for the detection of N.
      gonorrhoeae and C. trachomatis by PCR. RESULTS: Of 301 assessable patients, there
      were 14 cases of gonorrhoea, 21 cases of chlamydia, and 1 case of dual infection
      detected by PCR. Most men (245/301; 81.4%) were asymptomatic, of whom 12 of 245
      (4.9%) had an infection detected compared with 24 of 56 (42.9%) in the
      symptomatic men (P < 0.001). Using a "< or = trace" cutoff, the overall value for
      the sensitivity of the LE test was 77.8% (95% confidence interval, 60.4-89.3),
      specificity 80.8% (75.4-85.2), positive predictive value 35.4% (25.2-47.1), and
      negative predictive value 96.4% (92.8-98.3). CONCLUSIONS: The negative predictive
      value of the LE test may be of use in determining which patients should proceed
      to specific diagnosis by nucleic amplification methods (e.g., PCR or ligase chain
      reaction). By limiting testing to patients with positive LE results, cost savings
      may be made, enabling the technology to be used in a wider community setting. The
      value of the LE test in higher prevalence populations with access to nucleic
      amplification testing remains to be established.

PMID- 9662769
TI  - A possible case of human T-cell lymphotropic virus type I transmission through
      sexual assault.

PMID- 9662770
TI  - Partner notification strategies for sexually transmitted diseases.

PMID- 9662771
TI  - Holding power of different pin designs and pin insertion methods in avian
      cortical bone.
AB  - OBJECTIVE: To measure pullout strength of four pin types in avian humeri and
      tibiotarsi bones and to compare slow-speed power and hand insertion methods.
      STUDY DESIGN: Axial pin extraction was measured in vitro in avian bones. ANIMAL
      POPULATION: Four cadaver red-tailed hawks and 12 live red-tailed hawks. METHODS:
      The pullout strength of four fixator pin designs was measured: smooth, negative
      profile threaded pins engaging one or two cortices and positive profile threaded
      pins. Part 1: Pins were placed in humeri and tibiotarsi after soft tissue
      removal. Part 2: Pins were placed in tibiotarsi in anesthetized hawks using slow
      speed power or hand insertion. RESULTS: All threaded pins, regardless of pin
      design, had greater pullout strength than smooth pins in all parts of the study
      (P < .0001). The cortices of tibiotarsi were thicker than the cortices of humeri
      (P < .0001). There were few differences in pin pullout strengths between threaded
      pin types within or between bone groups. There were no differences between the
      pullout strength of pins placed by slow-speed power or by hand. CONCLUSIONS:
      There is little advantage of one threaded pin type over another in avian humeri
      and tibiotarsi using currently available pin designs. There were few differences
      in pin pullout strengths between humeri and tibiotarsi bones. It is possible that
      the case of hand insertion in thin cortices minimizes the potential for wobbling
      and therefore minimizes the difference between slow-speed drill and hand
      insertion methods. CLINICAL RELEVANCE: Threaded pins have superior bone holding
      strength in avian cortices and may be beneficial for use with external fixation
      devices in birds.

PMID- 9662772
TI  - Prognosis factors for survival in cats after removal of a primary lung tumor: 21
      cases (1979-1994).
AB  - OBJECTIVE: To identify possible prognostic factors for survival time in cats with
      a primary lung tumor after surgical excision. STUDY DESIGN: Retrospective
      clinical study. ANIMAL POPULATION: 21 cats with histologically confirmed primary
      lung tumors removed surgically. METHODS: Medical records for cats treated between
      1979 and 1994 at 14 participating veterinary referral hospitals were reviewed.
      RESULTS: After surgical resection and recovery, 18 cats died from metastatic
      disease with a median survival time of 115 days (range, 13 to 1,526 days). Three
      cats were lost to follow-up at 119 days, 251 days, and 410 days after the
      surgical procedure. Contingency table analysis to determine if an association
      existed between clinical findings (breed, age, gender, body weight, clinical
      signs, duration of clinical signs, and radiographic findings) or histological
      features and survival time was performed. Only histological morphology of the
      primary lung tumor showed a significant association with survival time. Twelve
      cats with moderately differentiated tumors had a significantly longer survival
      time (median, 698 days; range, 19 to 1,526 days) than the nine cats with poorly
      differentiated tumors (median, 75 days; range, 13 to 634 days). CONCLUSIONS:
      Surgical resection of a solitary primary lung tumor in cats is indicated.
      CLINICAL RELEVANCE: A poor prognosis for long-term survival is warranted for
      those cats having a poorly differentiated primary lung tumor.

PMID- 9662773
TI  - Hypothermic storage of feline kidneys for transplantation: successful ex vivo
      storage up to 7 hours.
AB  - OBJECTIVE: To describe the effect of hypothermic storage on transplanted feline
      kidneys. STUDY DESIGN: Kidneys were stored in University of Wisconsin (UW) sodium
      gluconate (n = 3) or phosphate-buffered sucrose (n = 5) solutions before
      transplantation. ANIMAL POPULATION: Eight cats with renal failure and seven
      normal cats as kidney donors. METHODS: Kidneys were perfused through the renal
      artery with cold (10 degree C) storage solution and immersed in the solution on
      ice until transplantation. RESULTS: Mean ex vivo storage time was 4.8 +/- 0.36
      hours (range, 3.5 to 7 hours). Seven recipient cats survived surgery. Five of the
      cats had decreased serum creatinine concentrations from a mean of 8.2 mg/dL
      (range, 4.0 to 15.8 mg/dL) preoperatively to 1.7 mg/dL (range 1.3 to 2.2 mg/dL)
      within 4 days of surgery. In one cat, serum creatinine concentration dropped from
      15.1 to 3.7 mg/dL in 3 days, but the cat developed a ureteral stricture that
      required revision. One graft did not function, and the cat died on day 19. The
      mean postoperative survival time of cats that were discharged from the hospital
      (n = 6) was 254 days (range, 49 to 717 days) at the time of this report. Long
      term renal function (> 60 days postoperatively; n = 5) was excellent with mean
      serum creatinine concentrations of 1.6 +/- 0.15 mg/dL. CONCLUSIONS: Hypothermic
      storage is feasible for short-term preservation of feline kidneys. The maximal
      length of feasible storage remains unknown. CLINICAL RELEVANCE: Hypothermia
      protects against ischemia-induced nephron loss during ex vivo manipulation of the
      allograft and allows longer safe vascular anastomosis times. Short-term
      hypothermic storage also provides time to accommodate modifications in scheduling
      or anesthetic management of the recipient operation.

PMID- 9662774
TI  - Changes in third carpal bone articular cartilage after synovectomy in normal and
      inflamed joints.
AB  - OBJECTIVE: To determine if arthroscopic synovectomy in normal and inflamed joints
      had temporal or site-related effects on articular cartilage. STUDY DESIGN:
      Alterations in equine third carpal bone articular cartilage were studied at two
      time periods: groups 1 and 2 (6 weeks) and groups 3 and 4 (2 weeks) after
      synovectomy in normal (groups 2 and 4) and inflamed carpi (groups 1 and 3).
      ANIMAL POPULATION: 16 carpi from eight horses. METHODS: Biochemical and
      biomechanical properties of dorsal and palmar articular cartilage were determined
      by radioloabeling, proteoglycan (PG) extraction, chromatography, electrophoresis,
      and indentation testing. RESULTS: Synovectomy in inflamed joints produced the
      greatest concentration of newly synthesized PG in articular cartilage by 2 weeks.
      Synovectomy in normal joints produced significantly greater newly synthesized PG
      in articular cartilage by 6 weeks. Dorsal sites had greater newly synthesized and
      endogenous PG in some groups. Chromatographic profiles of newly synthesized PG
      demonstrated early and late PG peaks. Electrophoresis of late PG peak showed a
      toluidine blue-positive band that comigrated with human A1D1 PG monomer in the
      two groups with the most newly synthesized PG> This band was reactive with
      monoclonal antibody 1C6 specific for the hyaluronic acid-binding region of
      aggrecan. For the material properties evaluated, only Poisson's ratio was
      significantly decreased between groups as a function of time (6 weeks < 2 weeks).
      and this was most pronounced in the thicker dorsal sites. CONCLUSIONS:
      Synovectomy in inflamed joints produced site-specific, significantly greater
      responses in articular cartilage as compared with synovectomy in normal joints.
      CLINICAL RELEVANCE: Synovectomy may not be beneficial to the articular cartilage
      in inflamed joints.

PMID- 9662775
TI  - Ventral abdominal approach for laparoscopic ovariectomy in llamas.
AB  - OBJECTIVE: To evaluate a technique for laparoscopic ovariectomy by a ventral
      abdominal approach in the llama. STUDY DESIGN: Prospective evaluation. ANIMAL
      POPULATION: Six healthy adult female llamas, aged 2 to 6 years. METHODS:
      Laparoscopic ovariectomy was performed with the llamas in a 30-degree
      Trendelenburg position. The mesovarium and proper ligament of the ovary were
      isolated, and two Hulka clips were placed in opposite directions across each
      mesovarium and proper ligament of the ovary. Ovaries were removed through either
      the instrument cannula or instrument portal. RESULTS: The ovaries, mesovarium,
      and proper ligaments of the ovaries were easily identified using laparoscopy by a
      ventral abdominal approach. The Hulka Clip Applicator was easy to use, and the
      Hulka Clips provided secure hemostasis of the vessels within the mesovarium. Mean
      duration of surgery was 35 minutes (range, 17 to 85 minutes). Two llamas were
      depressed after surgery but improved within 24 hours. No other complications
      occurred during an 18-month follow-up period. CONCLUSIONS: Laparoscopic
      ovariectomy in the llama was facilitated by the use of Hulka Clips placed across
      the mesovarium and proper ligament of the ovary. CLINICAL RELEVANCE: Laparoscopic
      ovariectomy in the llama can be accomplished easily with few complications.

PMID- 9662776
TI  - Incomplete oblique sagittal fractures of the dorsal cortex of the third
      metacarpal bone in six horses.
AB  - OBJECTIVE: To describe incomplete oblique sagittal dorsal cortical fractures of
      the equine third metacarpal bone, their surgical repair, and subsequent
      performance of the horses. STUDY DESIGN: Retrospective examination of medical
      records and racing performance. ANIMAL POPULATION: Six Thoroughbred race horses,
      2 to 4 years of age. METHODS: Radiographic confirmation of all fractures preceded
      general anesthesia and surgical correction. Three fractures were treated by
      intracortical compression using screws placed in lag fashion, and five fractures
      were treated by osteostixis. Race records were reviewed for each horse to
      determine performance after surgery. RESULTS: Fractures were best observed on
      palmarodorsal radiographic projections. Three horses treated by intracortical
      compression returned to racing, but fracture recurred in one horse and was
      treated by osteostixis. This horse and the other three horses treated by
      osteostixis raced after surgery. CONCLUSIONS: Horses with incomplete oblique
      sagittal fractures of the dorsal cortex of the third metacarpal bone can race
      after surgical management of the fracture by screws placed in lag fashion or
      osteostixis. The authors' preferred surgical procedure for managing this fracture
      is osteostixis. CLINICAL RELEVANCE: Palmarodorsal radiographic projections of the
      third metacarpal bone are recommended in young Thoroughbred race horses suspected
      of having dorsal metacarpal stress fractures.

PMID- 9662777
TI  - Flexor carpi ulnaris (humeral head) muscle flap for reconstruction of distal
      forelimb injuries in two dogs.
AB  - OBJECTIVE: To describe the use of the humeral head of the flexor carpi ulnaris
      muscle as a rotational flap for reconstruction of distal antebrachial, carpal,
      and metacarpal injuries in two dogs. STUDY DESIGN: Description of clinical cases.
      RESULTS: Local rotation of the humeral head of the flexor carpi ulnaris muscle
      provided coverage of the carpal and carpometacarpal bones and joint structures
      exposed by soft tissue avulsion. CONCLUSIONS: The distal portion of the humeral
      head of the flexor carpi ulnaris muscle can be used as a local muscle flap.
      CLINICAL RELEVANCE: Early soft tissue coverage of large wounds to the carpal and
      metacarpal regions can be accomplished without resorting to a more technically
      difficult procedure, such as a free vascularized flap transfer.

PMID- 9662778
TI  - Splenocaval shunting for alleviation of portal hypertension in a dog: a case
      report.
AB  - OBJECTIVE: To describe the construction and use of a splenocaval shunt to prevent
      portal hypertension in a dog with iatrogenic rupture and subsequent complete
      occlusion of an intrahepatic portosystemic shunt (IPSS). STUDY DESIGN: Case
      report describing a single, client-owned animal. RESULTS: During dissection, the
      back wall of an IPSS was torn. Complete shunt occlusion was required to control
      the hemorrhage. This resulted in the development of life-threatening portal
      hypertension. Emergency splenocaval shunt construction reduced the portal
      pressure from 47 to 20 cm H2O. The dog experienced minimal postoperative
      complications. A second surgical procedure was performed a month later to
      completely ligate the splenocaval shunt. CONCLUSIONS: A splenocaval shunt can be
      used to divert blood from the portal to the systemic circulation to control
      portal hypertension. In this dog, it resulted in a successful outcome with few
      complications. CLINICAL RELEVANCE: The splenocaval shunt could be constructed
      before the dissection of a difficult IPSS if problems arise as occurred in the
      dog described in this report. Complete IPSS occlusion can be performed without
      development of portal hypertension.

PMID- 9662779
TI  - Fragmented coronoid process and incomplete ossification of the humeral condyle in
      a rottweiler.
AB  - OBJECTIVE: To describe incomplete ossification of the humeral condyle and
      fragmentation of the medial coronoid process in a Rottweiler. STUDY DESIGN:
      Clinical report. ANIMAL POPULATION: A 4-year-old sexually intact male Rottweiler.
      METHODS: Physical examination, radiography, and computed tomography of both elbow
      joints were performed initially. Drill holes were made across the humeral condyle
      to promote ossification. Radiography and computed tomography were repeated 14
      weeks later. Radiography was repeated 15 months later. A mild intermittent
      lameness remained. RESULTS: Preoperatively a radiolucent line was present across
      the right humeral condyle. This radiolucent line remained unchanged 14 weeks
      after drill holes were made across the condyle. CONCLUSIONS: Incomplete
      ossification of the humeral condyle is present in Rottweilers. CLINICAL
      RELEVANCE: Incomplete ossification of the humeral condyle is present in
      Rottweilers and may coexist with fragmentation of the medial coronoid process in
      that breed. The radiographic diagnosis may be difficult because precise
      positioning is required to see the area of incomplete ossification. Computed
      tomography may be required to confirm the presence of incomplete ossification of
      the humeral condyle. Drilling holes across the humeral condyle does not appear to
      lead to union of the area of incomplete ossification.

PMID- 9662780
TI  - Use of buccal mucosal flaps for the correction of congenital soft palate defects
      in three dogs.
AB  - OBJECTIVE: To present an alternative surgical technique for the repair of soft
      palate defects in dogs. ANIMAL POPULATION: Three Foxhound cross dogs. METHODS:
      Bilateral buccal mucosal flaps, based at the palatoglossal arches, were raised.
      One flap was rotated so that the mucosal side created the floor of the
      nasopharynx. The second flap was rotated so that the mucosal side formed the roof
      of the oropharynx. The mucosa of the remnant of the soft palate and the
      pharyngeal walls was incised and the flaps sutured to these free mucosal edges.
      The caudal ends of the two flaps were sutured to each other. RESULTS: Complete
      closure of the soft palate defect was obtained in all three dogs. The dogs were
      monitored for between 1.5 and 3 years postoperatively, and no long-term problems
      were encountered. CONCLUSIONS: This surgical technique resulted in an excellent
      functional separation of the oropharynx and nasopharynx and allowed
      reconstruction of a large bilateral soft palate defect. CLINICAL RELEVANCE: By
      using the buccal mucosal flaps, as described in this report, a tension-free
      closure of large soft palate defects can be obtained, thereby eliminating a major
      cause of failure of this type of reconstructive surgery.

PMID- 9662781
TI  - Ameroid constrictors in portosystemic shunts.

PMID- 9662782
TI  - A comparison of indirect blood pressure monitoring techniques in the anesthetized
      cat.
AB  - OBJECTIVE: To determine the accuracy of three indirect blood pressure monitoring
      techniques (oscillometric technique [OS], Doppler [DOP], and optical
      plethysmography [OP] [blood pressure determined with a pulse oximeter waveform])
      when compared with direct arterial pressure measurement in cats. STUDY DESIGN:
      Prospective study. ANIMAL POPULATION: Eight healthy (five female, three male),
      domestic short-hair cats weighing 3.5 +/- 0.8 kg METHODS: Cats were anesthetized
      with isoflurane. The inspired concentration of isoflurane was adjusted to produce
      mild hypotension (80 to 100 mm Hg direct systolic), moderate hypotension (60 to
      80 mm Hg direct systolic), and severe hypotension (< 60 mm Hg direct systolic).
      Indirect pressure measurements were obtained from the thoracic limb and compared
      with concurrent direct measurement using regression analysis and a modification
      of Bland and Altman's technique. RESULTS: All three techniques underestimated
      systolic pressure. OS produced the best prediction of systolic pressure with a
      bias +/- precision of -15.9 +/- 8.1 mm Hg. DOP and OP were relatively inaccurate
      with a bias +/- precision of -25 +/- 7.4 mm Hg and -25 +/- 7.5 mm Hg. All three
      techniques correlated well with direct pressure with r values of 0.81, 0.88, and
      0.88 for OS, DOP, and OP. DOP and OP provided an accurate prediction of direct
      mean arterial pressure with a bias +/- precision of -0.8 +/- 6 mm Hg and 0.6 +/-
      5.5 mm Hg. Correlation was good between DOP and mean arterial pressure with r =
      0.89. Correlation was also good between OP and mean arterial pressure with r =
      0.90. CONCLUSIONS: OS provided the most accurate prediction of direct systolic
      pressure. DOP and OP provided a good prediction of mean arterial pressure in the
      cat. CLINICAL RELEVANCE: All three of these techniques are useful for detecting
      trends. Direct monitoring of blood pressure should be considered if accurate
      blood pressure measurement is required.

PMID- 9662783
TI  - Cardiovascular effects of enoximone and epinephrine on heparin reversal with
      protamine in conscious dogs.
AB  - OBJECTIVE: To compare enoximone with epinephrine as treatments for the
      cardiotoxic effects of protamine sulfate. STUDY DESIGN: Prospective randomized
      study. ANIMAL POPULATION: 12 healthy cross-bred dogs weighing 23 +/- 4 kg.
      METHODS: The dogs were anesthetized with xylazine and ketamine to allow
      instrumentation. Femoral arterial and venous catheters were inserted for pressure
      monitoring and to allow drug infusion. A thermodilution catheter mounted with a
      fast response thermistor was inserted into the pulmonary artery via the jugular
      vein to measure cardiac output and right ventricular volumes. Heparin 300
      units/kg followed by protamine 4.5 mg/kg were administered 45 minutes after the
      xylazine/ketamine. Four animals were not treated (controls), four received
      enoximone, and four were given epinephrine. Cardiopulmonary parameters were
      monitored for a period of 30 minutes. RESULTS: Cardiac index was 104 +/- 15
      mL/kg/min in the enoximone group, 72 +/- 13 mL/kg/min in the epinephrine group,
      and 63 +/- 10 mL/kg/min in the control group (P < .05 enoximone versus control
      and epinephrine). Right ventricular end systolic volume was 18 +/- 3, 27 +/- 4,
      and 29 +/- 6 mL in the enoximone, epinephrine, and control groups (P < .05
      enoximone versus control and epinephrine). There were no differences in mean
      arterial pressure or pulmonary and systemic vascular resistance between the
      groups. CONCLUSION AND CLINICAL RELEVANCE: In this study, enoximone was more
      effective than epinephrine at reversing the hemodynamic changes associated with
      protamine sulfate administration.

PMID- 9662784
TI  - Epidural injection of ketamine for perineal analgesia in the horse.
AB  - OBJECTIVE: To determine the analgesic, sedative, and cardiopulmonary effects of
      epidural ketamine in the horse. ANIMAL POPULATION: Six healthy horses (three
      males and three females) weighing between 350 and 450 kg. METHODS: Three doses of
      ketamine were selected (0.5, 1, 2 mg/kg). Two months before the beginning of
      experiments, the carotid artery was exteriorized, and 1 week before experiments
      began, an epidural catheter was placed percutaneously in all animals with the tip
      located 12 cm cranially in the midsacrum. One week later, either saline (control)
      or one of three doses of ketamine was injected epidurally. Each animal received
      each ketamine dose and saline in random order at 1-week intervals. Ketamine was
      diluted in saline 0.9% before the experiment, and the volume used was adjusted to
      horse size and correlated to clinically used volumes. All the animals received a
      standard noxious stimulus consisting of needle insertion into the skin and deep
      muscle using a 3-point scale for scoring the response. A second scale was used to
      score the degree of sedation. The response to a noxious stimulus, the degree of
      sedation, and arterial blood pressure were assessed at previously determined
      intervals: before drug and 2, 5, 10, and 15 minutes and every 15 minutes to 210
      minutes after ketamine or saline administration. Arterial blood samples were
      drawn for blood gas analysis before drug and at 15, 30, 60, and 90 minutes.
      RESULTS: All the tested doses of ketamine were effective in producing analgesia
      of the tail, perineum, and upper hindlimb. Total tail and perineal analgesia
      times were similar depending on dosage (30 minutes for 0.5 and 1.0 mg/kg and 75
      minutes for 2.0 mg/kg). A sedative effect of ketamine was also observed in a dose
      response manner with a peak effect between 15 and 30 minutes postadministration.
      No cardiopulmonary effects were observed with any dose of ketamine. CONCLUSIONS:
      Results indicate that epidurally administered ketamine in the horse produces
      local spinal and central nervous system effects with analgesia and sedation but
      minimal cardiopulmonary effects. CLINICAL RELEVANCE: Further studies are required
      to determine whether the analgesia is sufficient for surgery.

PMID- 9662785
TI  - [100-year history of the Perm Scientific-Industrial Complex "Biomed"].

PMID- 9662786
TI  - [Development of scientific trends with respect to vaccines and serum preparations
      at the Perm Scientific-Industrial Complex "Biomed"].

PMID- 9662787
TI  - [Anti-endotoxic immunity: formation, functions and detection].

PMID- 9662788
TI  - [Problem of pure antibodies and its realization in works on the development of
      immunoenzyme test-systems].

PMID- 9662789
TI  - [Reaction of the bacteriosorption of immune complexes and its use for the
      evaluation and antitoxic serum].
AB  - The reaction of the bacteriosorption of immune complexes (RBIC), based of on the
      avidity of horse IgG (T) to protein A in interaction with complement antigen, is
      proposed. The possibility of using RBIC for the evaluation of the titer of native
      antitoxic sera and the degree of the enzymolysis of specific antitoxins with
      pepsin has been shown.

PMID- 9662790
TI  - [Development of a test system for detection of anti-endotoxic immunity in young
      children, healthy donors and some groups of therapeutic patients].
AB  - The content of antibodies to soluble lipid A detritus was studied with the use of
      the enzyme immunoassay techniques. Some regularities of anti-endotoxic immunity
      were established: the elevated level of anti-lipid A antibodies in chronic
      bronchial tree diseases of bacterial etiology. On the other hand, cases of severe
      purulent septic infections in young children were found to be accompanied by a
      considerable decrease in the titer of anti-endotoxic antibodies. The approaches
      to the therapy of diseases caused by Gram-negative bacteria by means of specific
      immunoglobulins are discussed.

PMID- 9662791
TI  - [Coagglutination test. Its improvement and use in the production of anatoxins].
AB  - The reactor technology for obtaining suspensions of Staphylococcus aureus (strain
      Cowan 1) with active protein A was developed. On the basis of the sensitization
      of bacterial suspensions with antitoxic rabbit sera staphylococcal reagents to
      diphtherial, gas gangrene (perfringens, oedematiens), botulinic toxins-toxoids
      were obtained and for the first time the coagglutination test with toxoids was
      carried out. More sensitive "specifically directed" reagents for the
      coagglutination test were obtained; for this purpose bacterial suspensions were
      sensitized with pure antibodies isolated from rabbit immune sera by
      immunosorption. The possibility of using the coagglutination test with
      specifically directed staphylococcal reagents for the rapid evaluation of the
      dynamics of toxin formation in reactors for the titration of purified toxoids,
      for the control of the purification of toxoids by ultrafiltration, as well as for
      the evaluation of the sorption-desorption of toxoids in the production of the
      corresponding preparations, was shown.

PMID- 9662792
TI  - [Feasibility of determining occult blood using rapid serologic methods].
AB  - The possibility of obtaining antibodies to human hemoglobin and erythrocytes and
      their use for the detection of hidden blood in different biological fluids was
      studied. The test system, based on the reaction of coagglutination with the use
      of protein A of Staphylococcus aureus Cowan 1 and magnetic sorbent, is proposed.

PMID- 9662793
TI  - [Scientific achievements in the field of anatoxin production].

PMID- 9662794
TI  - [Use of membrane separation methods in the production of Clostridium perfringens
      toxoid].
AB  - The dynamics of ultrafiltration was found to depend on the composition of the
      nutrient medium in which C.perfringens toxin accumulated. A new composition of
      casein-pancreatic medium with the reduced content of high-molecular peptides
      ensuring a high effect of membrane separation was developed. The influence of the
      main factors (pressure, concentration, the number of diafiltration cycles) on the
      characteristics of the membrane separation of type A C.perfringens culture. The
      optimum conditions for the purification of C.perfringens toxin by ultrafiltration
      were established with due regard to the data obtained in this investigation.
      Toxin concentrates were found to contain a fraction inhibiting their sorption
      capacity, and the method of the elimination of the inhibiting component was
      developed. C.perfringens toxoids, considerably exceeding commercial preparations
      in specific activity and immunogenic potency, were obtained.

PMID- 9662795
TI  - [Detection of exotoxins of the pathogens of anaerobic gas infection using enzyme
      immunoassay].
AB  - To detect the exotoxins of the causative agents of the main anaerobic gas
      infection (Clostridium perfringens, C.oedematiens, C.histolyticum, C.septicum) a
      rapid and easily reproducible variant of the enzyme-linked immunosorbent assay
      (ELISA), based on the use of the sandwich modification activated due to avidin
      biotin interaction, was proposed. The possibility of using the avidin-biotin
      variant of ELISA for the detection of C.perfringens, C.oedematiens,
      C.histolyticum and C.septicum toxins in experimental gas gangrene in guinea pigs
      was shown. The method made it possible to reproducibly detect 0.02-0.2 ng of
      antigens (gangrene toxins-toxoids) with the immunoassay being highly specific.

PMID- 9662796
TI  - [Certification of a kit for immunologic tests].
AB  - A diagnostic kit for the determination of IgG antibodies to diphtheria toxin
      ("Abion", Germany) the use of analytical columns "Abicap" was studied in the
      specialized laboratory of the Tarasevich State Control Institute with a view to
      determine the possibility of its official registration in the Russian Federation.
      The kit was evaluated by the following criteria: the correspondence of the
      specified properties of the preparation to those actually observed; meeting the
      norms stated in the documents supplied with the kit and WHO requirements; the
      presence of advantages in comparison with the enzyme immunoassay. In the course
      of the trial positive results were obtained on all these points.

PMID- 9662797
TI  - [A multistage metrologic approach to the problem of evaluation of the results of
      the quantitative enzyme immunoassay determination of antitoxic antibodies].
AB  - To evaluate a kit for the enzyme immunoassay (ELISA), the metrological approach
      was used: the total error of the method for the quantitative determination of
      antibodies, regarded as a multistage process, was determined as the result of the
      accumulation of errors made in measurements at different stages. The proposed
      algorithm made it possible to attest the positive control serum, to determine the
      total error of measurements, to mark a linear section in a limited range of
      values on a graduation diagram. This led to obtaining well-grounded results,
      comparable with the results of the reaction of neutralization at good correlation
      (lc = 0.9).

PMID- 9662798
TI  - [Physico-chemical and immunobiological properties of the ribosomal preparations
      of Clostridium perfringens, type A].
AB  - Ribosomes, sufficiently purified by physicochemical criteria (with the
      RNA/protein ratio equal to 1.6 - 1.7), were isolated from disintegrated
      C.perfringens cells, type A, strain BP6K, by ultracentrifugation or by
      fractionation with polyethylene glycol. The purified conjugates of ribosomes and
      C.perfringens toxoid, absorbed on aluminum hydroxide, were obtained. The
      ribosomal preparations had low toxicity and high protective activity: when used
      in a dose of 6 binding units, they protected guinea pigs and mice inoculated with
      8 - 9 LD50 of C.perfringens culture.

PMID- 9662799
TI  - [Contribution of the Scientific-Industrial Complex "Biomed" to the study of
      problems of rickettsiology and chlamydiology].

PMID- 9662800
TI  - [Main principles of the construction of rickettsial antigens preparations and
      prospects for their improvement].

PMID- 9662801
TI  - [Immunobiological properties of phospholipid antigens of Rickettsia prowazekii
      incorporated into rickettsial liposomal preparations].
AB  - In this article materials on obtaining rickettsial liposomal preparations on the
      basis of R.prowazekii phospholipid antigen and chemical typhus vaccine are
      presented. Electron microscopic studies revealed the formation of liposomes in
      this system. Liposomal preparations were not hemotoxic and produced no toxic
      action in experiments on guinea pigs and white mice. Phospholipid antigens
      incorporated into liposomal preparations were found to produce a potentiating
      effect on the immunogenic properties of chemical typhus vaccine. The adjuvant
      properties of rickettsial phospholipids incorporated into liposomes on the basis
      chemical typhus vaccine were registered.

PMID- 9662802
TI  - [Development of the technology of the purification of Coxiella burnetii from
      components of culture medium].
AB  - The technology of the purification of C.burnetii from the yolk-sac components of
      the cultivation medium, including differential centrifugation, membrane
      filtration, enzymatic hydrolysis, the standardization of the preparation thus
      obtained and its stabilization by the method of lyophilization, was developed.
      Antigens, prepared in accordance with this technology, were sufficiently active
      and highly specific. The possibility of their use in different serological tests
      (the complement fixation test and the indirect fluorescent analysis) was studied.
      In addition, these antigens were found to have good capacity for sorption on the
      solid-phase carrier (plates) and to be suitable for use in such highly sensitive
      test as the enzyme immunoassay.

PMID- 9662803
TI  - [Development and use of erythrocyte diagnosticums for the detection of
      rickettsiae and antibodies to them].
AB  - The hemosensitizing activity of different fractions of antirickettsial sera,
      obtained from horses in the process immunization (primary sera) and remote
      reimmunization (reimmune sera), was studied. The study revealed that in the
      process of hemosensitization the leading role was played by IgM of primary sera
      and IgG of reimmune sera, the latter having the most active hemosensitizing
      properties. The inhibiting action of ballast proteins on the process of
      hemosensitization was demonstrated. On the model of antirickettsial sera obtained
      at different stages of the immunization of animals with R.prowazekii the
      possibility of using the reaction of antigen neutralization, made with the use of
      different working doses of the antigen, for the differentiation of primary and
      repeated immune response was shown. The mechanism of such modified variant of the
      reaction of antigen neutralization is considered and the possibility of using it
      for the differentiation of epidemic typhus and Brill's disease is discussed.

PMID- 9662804
TI  - [Feasibility of constructing species-specific antigenic erythrocyte diagnosticum
      for the detection of antibodies to Rickettsia prowazekii].
AB  - Species-specific antigenic erythrocyte diagnosticum (SAED) for the detection of
      antibodies to R.prowazekii was developed. The cells used as the basis for the
      preparation of the antigenic erythrocyte diagnosticum were formulated and tanned
      sheep red blood cells (FT-SRBC). Original indication antigens, solubilized with
      Triton X-100 from common R.prowazekii antigen for the complement fixation test,
      the antigen neutralization test and the fluorescent analysis, were used as
      sensitin. The optimum parameters for sensitizing FT-SRBC were established. The
      SAED thus obtained was stabilized by the method of lyophilization. In a separate
      series of experiments the specificity and activity of SAED were studied in
      comparison with those of preparations obtained with the use of different
      sensitins. The newly developed SAED was shown to be highly specific.

PMID- 9662805
TI  - [Antigenic and immunoglobulin preparations for the diagnosis of coxiellosis in
      the system of conjugated unidirectional serologic reactions].
AB  - The methods for obtaining antigenic and immunoglobulin preparations intended for
      the rapid serological diagnosis of coxiellosis were developed. The cells used as
      the basis for their preparation were formulated tanned sheep red blood cells. As
      sensitin, rabbit anti-C.burnetii immunoglobulin was used. The capacity for the
      detection of C.burnetii antigens in the passive hemagglutination test and
      specific antibodies in the passive agglutination test with the use of the our
      immunoglobulin erythrocytic diagnosticum was studied. To construct coxiellosis
      antigenic erythrocytic diagnosticum, the complex of membrane antigens obtained
      from C.burnetii strain M-44 was used as sensitin. The positive results of the
      approbatory trial of the erythrocytic diagnosticums made it possible to recommend
      both preparations for use in laboratory practice in the system of conjugated
      unidirectional serological reactions.

PMID- 9662806
TI  - [Diagnosis of chlamydial infections in man and animals].
AB  - In this article the problems of immunodiagnostics of generalized and local
      chlamydial infections are discussed. Extensive material is used for the
      substantiation of the expediency of using serological methods for diagnosing
      zoonotic and anthroponotic chlamydial infections. A rational scheme of using the
      passive hemagglutination (PHA) test and the complement fixation test for the
      detection of generalized chlamydial infections, as well as the PHA test and the
      indirect immunofluorescence test for diagnosing urogenital chlamydial infections.

PMID- 9662807
TI  - [Half a century of experience in the experimental and clinical study of virus
      infections].

PMID- 9662808
TI  - [Affinoleikin--a biopharmaceutical preparation for instructive anti-infective
      immunotherapy in cellular immunodeficiency].

PMID- 9662809
TI  - [The immunomodulating activity of a transfer-factor preparation transflavin,
      specific to tick-borne encephalitis virus].
AB  - Transflavin, a transfer-factor preparation specific to tick-borne encephalitis
      virus, was experimentally shown to possess immunomodulating action. The
      immunomodulating action of this preparation could be observed in a dose of 1 D (1
      D being equivalent to 5 x 10(8) lymphocytes), which was manifested by an increase
      in the phagocytic activity of neutrophils and macrophages, a rise in the amount
      of T-lymphocytes, an increase in rosette formation, the number of antibody
      forming cells, increased proliferation on T- and, to a lesser extent, B-cell
      mitogens, the restoration of the T-dependent expression of lymphocyte receptors,
      inhibited by trypsin. Transflavin in doses of 0, 1 and 10 D suppressed primary
      immune response. The probable mechanisms of the immunomodulating action of the
      Transflavin under study is discussed.

PMID- 9662810
TI  - [Antigenemia and circulation of specific immune complexes in the asymptomatic
      course of tick-borne encephalitis].
AB  - The frequency of the detection of tick-borne encephalitis (TBE) virus antigens,
      carried out by the method of fluorescent antibodies with the use of erythrocytic
      immunosorbent, in the blood of persons bitten by virus-carrying ticks, but with
      no signs of the clinical manifestation of the infection changed from 5.7 +/- 2.4%
      to 13.8% of cases with different time elapsed after infection, constituting, on
      the average, 8.5 +/- 1.4%. The detection of the antigen in the examination of
      patients varied from 35.8 +/- 6.6% to 45.4 +/- 10.6%, the average figure being
      39.8 +/- 3.9%. Antigenemia was more frequently detected after infection by
      virulent TBE virus than after infection by a low-virulent strain of the virus.
      The frequency of the detection of specific immune complexes in cases of the
      asymptomatic course of this infection (28.8 +/- 6.7%) was somewhat lower than in
      TBE patients (36.0 +/- 3.0%). But the difference between these figures was not
      significant (p > 0.1), which was probably indicative of the relatively weak
      formation of specific immune complexes in cases of clinical manifestations of TBE
      in spite of considerable antigenemia in TBE patients and their sufficiently
      active formation in the asymptomatic course of the disease.

PMID- 9662811
TI  - [Lymphocytes as markers of etiologic and pathogenetic factors of infectious
      diseases].
AB  - In the examination of patients with the dermato-respiratory syndrome, peptic
      ulcer, pyoderma and surgical wounds for their immune status for the expression of
      receptors of immunocytokins (interferon, interleukin-2), autocoids (histamine,
      serotonin), neuromediators (acetylcholine, dopamine, epinephrine, norepinephrine)
      and for the presence of Staphylococcus aureus and Helicobacter pylori antigens
      have revealed that lymphocytes are the markers of the presence of infection in
      the body, pathogenetic systemic and intersystemic disturbances, adequately chosen
      therapy and its effectiveness.

PMID- 9662812
TI  - [Glycolytic metabolites and adenosine triphosphoric acid in the herpes-infected
      eye].
AB  - In the tissues of the herpes-infected eye of a rabbit the content of adenosine
      triphosphoric acid (ATP), glucose and pyroracemic acid decreases and the level of
      lactic acid rises, i.e. anaerobic glycolysis prevails over the aerobic
      decomposition of glucose. A sharp decrease in the amount of ATP in the cornea and
      the iris in herpetic keratitis is due to the increased consumption of ATP for the
      synthesis of DNA and polypeptides of herpes simplex virus, as well as to
      disturbances in the oxidation transformations of glucose linked with the
      increased proportion of anaerobic glycolysis.

PMID- 9662813
TI  - [Preparing natural biologically active preparations as a new trend in research at
      the Scientific-Industrial Complex "Biomed"].

PMID- 9662814
TI  - [Immunotropic effects of molokin].
AB  - The immunopharmacological properties of Molokin, a polypeptide preparation
      obtained from the milt of fish of the salmon family, were studied. The Molokin
      was shown to activate the phagocytosis of macrophages, to increase the number of
      antibody-forming cells, to elevate antibody titers in mice with high reactivity
      (CBA) and low reactivity (C57BL).

PMID- 9662815
TI  - [Effect of vermin on immunity].
AB  - The influence of vermin of immunity was studied in experiments on mice. This
      preparation was shown to have immunomodulating action. Of three doses under test
      (0.0025, 0.25 and 25 mg/kg), the preparation used in the first two doses
      exhibited immunostimulating action and in the third dose, immunosuppressing
      action. The realization of the immunotropic effects of vermin was linked with the
      influence of the preparation of B-cell-mediated immunity and the synthesis of
      antibodies.

PMID- 9662816
TI  - [Probiotics: retrospective view, problems and achievements of the scientific
      industrial practice at the Scientific-Industrial Complex "Biomed"].

PMID- 9662817
TI  - [Development of methods for the stabilization of biomass in the preparation of
      medicinal forms of lactobacterin].
AB  - In this work the problems of obtaining medicinal forms of lactobacterin with the
      use of nontraditional methods for the stabilization of biomass are considered.
      The data on the stability of tablets, suppositories and microgranules of the
      preparation prepared on the basis of immobilized cells, are presented.

PMID- 9662818
TI  - [Increasing the effectiveness of the therapeutic action of probiotics].
AB  - The problems of the optimization of the therapeutic action of probiotics are
      discussed. Their use in combination with vitamin-enriched food additives is
      recommended. Balsams "Beryozka" and "Zolotoi koren" have been found to promote
      the adhesive capacity of bifidobacteria and lactobacteria. At the same time
      "Zolotoi koren" also enhances the functional activity of lactobacilli. The
      increase of the adhesive capacity and metabolic activity of automicroflora on one
      hand and the pronounced biostimulating effect of the balsams on the other hand
      may ensure a sufficiently high level of the colonization resistance of the body.

PMID- 9662819
TI  - [Use of silver sols as markers for immunoassay on microtiter plates].
AB  - Some basic characteristics of silver sols, facilitating their use as possible
      markers for the enzyme immunoassay on microtitration plates, were studied.
      Dispersion characteristics of silver sols obtained from AgNO3 solutions with a
      concentration of 0.005-0.5%, as well as the efficiency of their detection with
      physical developers on the basis of methol, paraphenylene diamine and amidol,
      were determined. The aggregative stability of the sol and the protective effect
      of a number of nonionic detergents, synthetic and biopolymeric, were evaluated.
      Similar sensitivity at the level of 1 ng/ml was attained in the comparative
      detection of lgG adsorbed on microtitration plates with the use of
      immunoperoxidase conjugate and silver immunosols. The possibility of using silver
      sols in the enzyme immunoassay as an alternative to enzymatic markers was shown.

PMID- 9662820
TI  - [Self-regulation of Salmonella minnesota populations in the process of induced
      autolysis].
AB  - The dynamics of the populations of S. minnesota S- and R-forms in autolysis,
      induced by multifactor methods with and without the use of oleic acid, the analog
      of autolysis-activating autoregulator, was studied. In the process of autolysis
      the optical density (OD) of cell suspension, the total number of bacteria, the
      number of anabiotic refractile cells and the number of colony-forming units (CFU)
      were analyzed. The comparative analysis of the kinetics of the induced autolysis
      of Salmonella S- and R-forms was carried out, the phases of autolysis kinetics
      were determined. In the course of 1 hour following the induction of the autolysis
      of Salmonella S- and R-forms the paradoxical increase of the total number of
      bacteria and a sharp rise in the number of refractive anabiotic cells were
      observed simultaneously with the decrease of the OD of cell suspension and a
      sharp drop in the number of CFU; on hours 1-24 OP stabilized, the number of CFU
      increased, the total number of bacteria and the number of refractile cells
      decreased; on hours 24-48, simultaneously with the stabilization of the OD of
      cell suspension, the total number of salmonellae and the number of refractile
      anabiotic cells increased. The results thus obtained are indicative of the self
      regulation of Salmonella populations in induced autolysis and the necessity of
      controlling the process.

PMID- 9662821
TI  - [Use of recombinant alpha2-interferon and a complex immunoglobulin preparation
      for the treatment of chlamydiosis in pregnancy women].
AB  - The comparative study of the efficiency of using erythromycin and the combination
      of recombinant alpha 2-interferon with complex immunoglobulin preparation (CTP)
      for the treatment of chlamydiosis in pregnant women was made. 31 patients (group
      1) received erythromycin orally in doses of 500 mg twice a day for 15-14 days. 30
      other pregnant women were prescribed vaginal suppositories containing 300 mg. Of
      CTP, 2.0 x 10(6) I.U. of recombinant alpha 2-interferon and the intravaginal
      application of 15(2)-30 ml of solution containing the analogous amount of CTP and
      recombinant alpha 2-interferon. Immediately after treatment 7 patients with
      clinical signs of chlamydiosis were found in group 1 and 3 such patients, in
      group 2. In the pregnant women of group 1 the laboratory confirmation of
      chlamydial infection after treatment occurred 5.8 times more frequently than in
      the patients of group 2. In 7 women of group 1 vaginal candidiasis was diagnosed
      after treatment. In no case any side effects resulting from the proposed
      treatment were observed. Pathology caused by chlamydiae was shown to be absent in
      newborns and in parturient women who had received complex treatment for
      chlamydiosis.

PMID- 9662822
TI  - [Meningococcal lipopolysaccharide. Chemical structure and biological properties].

PMID- 9662823
TI  - [Bacterial IgA proteases].

PMID- 9662824
TI  - [Resolution of the Central Educational-Methodological Task Force on Microbiology,
      Virology and Immunology of the Ministry of Health of the Russian Federation].

PMID- 9662825
TI  - Difference between a testis and an ovary.

PMID- 9662826
TI  - Sex determination and primary sex differentiation in amphibians: genetic and
      developmental mechanisms.
AB  - Most amphibians lack morphologically distinguishable sex chromosomes, but a
      number of experimental techniques have shown that amphibian sex determination is
      controlled genetically. The few studies suggesting that environment influences
      sex determination in amphibians have all been conducted at temperatures outside
      of the range normally experienced by the species under study, and these effects
      probably do not occur under natural conditions. No sex-determining genes have
      been described in amphibians, and sex differentiation can be altered by treatment
      with exogenous steroid hormones. The effects of sex steroids vary extensively
      between species, and a variety of steroids can alter the sex ratios of treated
      larvae. The role of endogenous sex steroids in gonadal differentiation has not
      been fully explored; thus the natural role of steroids in amphibian gonadal
      differentiation is unknown. Sex steroid receptors have not been examined in
      amphibian gonads, and the mechanism of steroid action on the gonad is unclear. In
      addition to steroids, the thyroid hormones may play a role in gonadal
      differentiation. Pituitary gonadotrop(h)ins affect gonadal growth, but not
      differentiation or maturation of gonads. In addition to the issue of resolving
      the mechanisms underlying hormone action in gonadal differentiation, other
      debates concerning interactions between the developing gonads and the invading
      germ cells, and even the origin of the medullary and cortical portions of the
      developing gonads, remain unresolved. Studies examining links between sex
      determination and gonadal differentiation are needed. In addition, examinations
      of variation in steroidal effects on gonadal development in a phylogenetic
      context are lacking.

PMID- 9662827
TI  - Sexual differentiation of gonads as a function of temperature in the turtle Emys
      orbicularis: endocrine function, intersexuality and growth.
AB  - Emys orbicularis is a freshwater turtle with temperature-dependent sex
      determination. Estrogens play a major role in gonadal differentiation; when they
      are produced at high levels during the thermosensitive period (TSP), ovaries
      differentiate; when their synthesis is very low, testes differentiate. Estrogens
      are synthesized from androgens through the activity of aromatase. We examine here
      two aspects of gonadal differentiation, intersexuality and growth, in E.
      orbicularis. For gonadal intersexuality, we studied the relationship between
      gonadal aromatase activity and gonadal structure at 28.5 degrees C (pivotal
      temperature), from the beginning of TSP to hatching, and compared results to
      those obtained at 30 degrees C (producing 100% females) and 25 degrees C
      (producing 100% males). At 28.5 degrees C, both males and females are obtained.
      However, histological differentiation of gonads is delayed compared to that at 25
      degrees C and 30 degrees C, and an ovarian-like cortex of various thicknesses
      often develops at the surface of the male gonads; thus, several individuals
      display ovotestes at hatching. Despite important individual variations, the
      aromatase activity in ovaries differentiating at 28.5 degrees C increases during
      development as in ovaries differentiating at 30 degrees C. In most cases,
      however, activity is slightly lower than at 30 degrees C, and at the end of
      embryonic life, it becomes similar to that at 30 degrees C. In testes or
      ovotestes differentiating at 28.5 degrees C, aromatase activity remains low but
      is generally slightly higher than in testes at 25 degrees C; however, at the end
      of embryonic development, it becomes similar to that at 25 degrees C. Oocytes in
      the cortex of ovotestes begin to degenerate around hatching and continue to
      degenerate after hatching. Therefore, ovotestes evolve as testes. However, some
      oocytes may persist at the surface of testes up to the adult age. To estimate
      gonadal growth, the protein content was measured at different embryonic stages at
      25 degrees C and at 30 degrees C. Testis growth is fast during TSP, somewhat
      slower after TSP, and decreases around hatching. Ovary growth is much slower than
      testis growth during TSP and then accelerates up to the end of embryonic
      development. This differential growth is well correlated with gonadal aromatase
      activity--much higher at 30 degrees C than at 25 degrees C--and can be explained
      by the fact that during TSP, testicular cords develop at 25 degrees C whereas
      they are inhibited at 30 degrees C; the ovarian cortex begins to form during this
      period but grows chiefly after TSP. Both inhibition of testicular cord
      development and stimulation of cortex development are under the control of
      endogenous estrogens. In the case of ovotestes, slight increases in estrogen
      synthesis, compared to that in typical testes, are sufficient to induce the
      transient formation of an ovarian-like cortex although they do not inhibit the
      development of testicular cords.

PMID- 9662828
TI  - Temperature-dependent sex determination in the red-eared slider turtle, Trachemys
      scripta.
AB  - Temperature-dependent sex determination (TSD) in the red-eared slider turtle,
      Trachemys scripta, has been the subject of a variety of past studies. Incubation
      temperature appears to affect sex determination in a dose-dependent fashion. This
      suggests that temperature could be affecting a dosage-sensitive element in the
      sex-determination cascade. Sex determination in T. scripta is sensitive to
      estrogen, and data from many studies support the hypothesis that endogenous
      estrogen production may be involved in female sex determination. However, this
      hypothesis has not yet been evaluated through aromatase expression studies in
      this species. Several recent studies have cloned cDNAs for genes that could be
      involved in sex determination and/or sex differentiation. The cDNAs for SF-1 and
      MIS have been cloned in T. scripta, indicating that these may represent conserved
      elements in the sex-determination/sex-differentiation cascade of reptiles. The
      SOX9 cDNA also has been cloned in T. scripta (Spotila et al., '98), and it shows
      a sex-specific expression pattern. Future studies targeted at aromatase
      expression as well as the expression of factors such as SOX9, SF-1, and MIS will
      begin to provide a more comprehensive picture of the events involved in TSD in T.
      scripta. Further, such studies could help pinpoint the temperature-sensitive
      element(s).

PMID- 9662829
TI  - Sequence and expression analysis of WT1 and Sox9 in the red-eared slider turtle,
      Trachemys scripta.
AB  - Temperature-dependent sex-determination (TSD) is a phenomenon that has been
      characterized at the ecological, morphological, and endocrinological levels in
      some reptilian species. We have begun to investigate TSD at the level of
      molecular development by cloning, sequencing, and analyzing the expression of two
      genes, WT1 and Sox9, in the red-eared slider turtle Trachemys scripta. We
      obtained almost full-length cDNA clones for WT1 and Sox9 that were greater than
      73% identical to the human homologues at the nucleotide level. WT1 was expressed
      in urogenital tissue at all developmental stages examined (Yntema stages 12-20)
      at incubation temperatures that produce males (26 degrees C) or females (32
      degrees C). Sox9 was also expressed throughout these same stages, but some
      differences were observed. At both 26 degrees C and 32 degrees C Sox9 was
      expressed in the mesonephroi and the undifferentiated gonads until Yntema stage
      20, when only the gonad from the 26 degrees C embryos expressed a high level. In
      addition, there were two transcripts of Sox9 at all stages, but the relative
      proportion of the two transcripts differed at the two temperatures. Although the
      similarities in gene expression between a TSD species and other species with
      genotypically determined sex probably reflect the common features of
      organogenesis, differences may illustrate unique mechanisms for TSD.

PMID- 9662830
TI  - Embryonic brain-gonadal axis in temperature-dependent sex determination of
      reptiles: a role for P450 aromatase (CYP19).
AB  - Sex determination in egg-laying amniotes may be fundamentally different from that
      of placental mammals. The mammalian ovary differentiates normally in the absence
      of estrogen, whereas estrogen seems to be crucial for proper ovarian development
      in birds, reptiles, and lower vertebrates. Estrogens are produced normally by the
      biosynthetic conversion of androgens by the enzyme aromatase (CYP19), which is
      the sole mediator of this reaction. Aromatase inhibitors are capable of reversing
      females to males in turtles and chickens; therefore, a role for aromatase as the
      female sex determinant has been postulated for species in which sex determination
      is temperature-dependent. The entire aromatase coding sequence (1,509 base pairs)
      from adult terrapin ovaries was cloned, and Northern analysis indicates a single
      transcript (2.4 kb) for adult ovaries, whereas male and female brains express a
      2.4-kb as well as a 9.6-kb transcript. Using a sensitive (attomole sensitivity)
      competitive RT-PCR technique, aromatase transcript abundance was quantified
      during embryonic development for embryos treated with and without estrogen.
      Aromatase is transcribed, well before the temperature-sensitive, (stage 12), at
      both male and female temperatures in the brain. There is a switch to lower
      aromatase transcript abundance in the female brain concurrent with an exponential
      rise of aromatase transcript in the putative ovary. Transcripts remain below the
      detection limits in the putative testes but exhibit female levels of aromatase
      transcript when treated with estrogen. Aromatase mRNA levels are generally
      reduced in the brain by estradiol application. On the basis of these findings, we
      have postulated a model based on the competition between 5 alpha-reductase and
      P450 aromatase for androgen substrate in both the brain and the undifferentiated
      gonad to explain the TSD phenomenon in reptiles.

PMID- 9662831
TI  - Gene expression of steroidogenic enzymes in chicken embryonic gonads.
AB  - This paper reviews the molecular aspects of sex differentiation in birds and
      describes the sex-reversal effects of aromatase inhibitor on mRNA expression of
      steroidogenic enzymes. Although it is unknown whether the sex-determining gene
      resides in the W chromosome or whether a gene-dosage mechanism is involved in sex
      determination, it is clear that anti-Mullerian hormone (AMH) and androgen play a
      key role for testicular development, whereas estrogen is important for ovarian
      formation. Our in situ hybridization results demonstrated that mRNA expression of
      P450aromatase first takes place on day 6.5 of incubation exclusively in the
      female gonad. Treatment with aromatase inhibitor in ovo suppressed mRNA
      expression in genetic females. This suggests that ovarian development is promoted
      by aromatase expression via estrogen production. On the other hand, previous
      reports demonstrated that formation of the testis is accompanied by Sox9 and AMH
      mRNA expression, which start on days 6 and 8, respectively. This suggests that
      Sox9 plays an important role for the male determining pathway which leads to AMH
      expression and formation of the testis.

PMID- 9662832
TI  - Sex determination and gonadal development: a bird's eye view.

PMID- 9662833
TI  - Phenotypic manifestations during the development of the dominant and default
      gonads in mammals and birds.
AB  - The dominant embryonic gonad--testis in mammals and ovary in birds--secretes one
      or more morphogenetic substances that exert a major effect on the phenotype of
      the embryo. When deprived of their gonads, mammalian embryos develop into
      females, and avian embryos assume predominantly male characteristics, although
      retaining both oviducts. In order to fulfill their task of masculinizing the
      reproductive tract, mammalian testes grow and differentiate faster than ovaries.
      In birds the pattern is less straightforward. In 5-day-old embryos of White
      Leghorn chickens, sexual differentiation manifests itself in two different ways:
      (1) the gonads of ZZ embryos are larger, and on day 6 contain more protein and
      DNA than those of ZW embryos; (2) in both sexes, left gonads are larger than
      right gonads and contain a thick "germinal epithelium" capable of giving rise to
      an ovarian cortex under the influence of oestrogen. The pattern changes in
      embryos aged between 7 and 8 days, when the left gonad of ZW embryos outgrows all
      others, developing into an ovary, and when the bilateral asymmetry between left
      and right gonads increases in female embryos. A remnant of gonadal bilateral
      asymmetry is seen in the distribution of gonads in cases of true hermaphroditism
      in humans and other mammals. Whereas the initial fast growth of the mammalian
      testis is assumed to be due to one or more Y-chromosomal genes, that of the early
      avian testis is mostly simply explained as the effect in the disomic state of one
      or more genes on the Z chromosome. However, the later growth of the avian ovary
      is more likely to be due to oestrogen than to a direct gene effect. It is
      postulated that oestrogen has lost its power to determine ovarian development in
      mammals, in which both sexes are exposed to the oestrogen-rich environment of the
      uterus. Hence, the task of sex determination devolves on the fetal testis, whose
      early development and hormonal function are required to induce the male
      phenotype, the female phenotype arising in default mode.

PMID- 9662834
TI  - Evolution of the mammalian Y chromosome and sex-determining genes.
AB  - In mammals, male sex determination, as well as spermatogenesis, is controlled by
      genes on the Y chromosome. Evolutionary comparisons may be used to detect and
      test candidate genes for these functions, under the hypothesis that the rapid
      evolution of the mammalian Y chromosome causes it to contain few genes other than
      those with a critical function in male reproduction. Comparisons of the gene
      content of sex chromosomes from the three major groups of extant mammals
      (placentals, marsupials, and monotremes) show that part of the X chromosome, and
      a corresponding region of the Y, is shared by all mammals and must be very
      ancient, but part was added relatively recently. Evolution of the mammalian Y
      took place in several cycles of addition and attrition, as autosomal regions were
      added to the pseudoautosomal region of one sex chromosome, recombined onto the
      other, and degraded on the Y. This explains why most genes and pseudogenes on the
      Y chromosome have relatives on the X. The gene SRY itself is apparently no
      exception, being closely related to the highly conserved X-linked gene SOX3.
      Comparisons of SRY/SOX base sequence and gene location in the three groups of
      mammals suggest that SRY evolved from SOX3 relatively recently by mutation and
      loss of all sequences outside the HMG box. It is suggested here that, rather than
      acting as a transcriptional activator, the SRY gene acts to inhibit its paralogue
      SOX3, which in turn inhibits an ancient autosomal sex-determining gene SOX9.

PMID- 9662835
TI  - Cellular and molecular changes during sex differentiation of embryonic mammalian
      gonads.
AB  - Structural and molecular changes during sex differentiation and development of
      mammalian gonads from early embryonic phase until sexual maturity have been
      studied by morphologic and immunocytochemical methods in vivo and in experimental
      culture. The strategy has been to identify cellular macromolecules whose genes
      are differently expressed in the two sexes and to formulate a hypothetical
      regulatory chain of sex determination. This approach should provide new
      possibilities for finding the missing links between the final structural genes
      and the early regulatory genes, which are differentially expressed before and
      during gonadal differentiation. On the basis of accumulated structural and
      molecular evidence, the early epithelial differentiation from the precursor cells
      via cell aggregates to testicular cords or ovarian follicles is not sexually
      regulated. The biological consequences of sex determination in the
      differentiation of the genital organs include changes in the pattern formation of
      the gonadal epithelia and concomitant alterations in the synthesis and
      organization of the structural macromolecules.

PMID- 9662836
TI  - Sry and the testis: molecular pathways of organogenesis.
AB  - The gene Sry acts as a switch, initiating pathways leading to the differentiation
      of a testis rather than an ovary from the indifferent gonad (genital ridge) in
      mammals. The early events following Sry expression include rapid changes in the
      topographical organization of cells in the XY gonad. Sry must therefore initiate
      signaling pathways that direct male-specific patterns of proliferation,
      migration, cell-cell organization, and vascularization. We have identified an
      increase in male-specific proliferation by 12.0 days post coitum, while
      proliferation in the female gonad declines. We have also observed male-specific
      cell migration from the mesonephros into the gonad in a composite organ culture
      system in which gonads from wild-type mice (CD1) and mesonephroi from a
      transgenic strain expressing beta-galactosidase in all its cells (ROSA26) were
      grafted together in vitro at the indifferent stage of gonadogenesis. Migration
      depends on an active signal that requires the presence of a Y chromosome in the
      gonadal portion of the graft. The signals that trigger migration operate over
      considerable distances, suggesting either a long-range diffusible factor or the
      involvement of a rapid and efficient relay mechanism. Identification of the
      somatic cells contributed from the mesonephros with cell-specific markers
      indicated that some of the migrating cells were endothelial, revealing
      differences in processes of vascularization between male and female gonads. A
      second distinct population of migrating cells lay in close apposition to
      endothelial cells, and a third population occupied positions circumscribing areas
      of condensing Sertoli cells.

PMID- 9662837
TI  - Human sex determination.
AB  - Human sex determination is a fascinating topic, particularly at the level of
      molecular genetics, as it represents an excellent paradigm for mammalian organ
      development. Recent progress has seen the addition of several new pieces to this
      developmental jigsaw puzzle. In mammals, the Y chromosome is male determining,
      and encodes a gene referred to as TDF (testis-determining factor), which induces
      the indifferent embryonic gonad to develop as a testis. Subsequent male sexual
      differentiation is largely a consequence of hormonal secretion from the testis.
      In the absence of the Y chromosome, the testis-determining pathway fails to be
      initiated, and the embryonic gonad develops as an ovary, resulting in female
      development. (Ford et al. [1959] Lancet i:711; Jacobs and Strong [1959] Nature,
      183:302-303; Jost et al. [1973] Rec. Prog. Horm. Res., 29:1-41).

PMID- 9662838
TI  - [Genomic imprinting].

PMID- 9662839
TI  - [Population-based congenital birth defect registries in Spain].

PMID- 9662840
TI  - [Quick diagnosis of Prader-Willi and Angelman syndromes by means of methylation
      test by PCR].
AB  - OBJECTIVE: Angelman (AS) and Prader-Willi (PWS) syndromes are two different
      neurogenetic diseases caused by a deficiency of maternal (AS) or paternal (PWS)
      contributions of the region 15q11-13. Molecular diagnosis of these pathologies
      can be accomplished by several techniques: DNA polymorphism (microsatellite)
      analysis, cytogenetic techniques of fluorescent in situ hybridization (FISH) and
      methylation test by Southern blot (SB), with the latter being the most reliable.
      Recently, a new technique, based on the study of methylation through treatment
      with sodium bisulphite and subsequent polymerase chain reaction (PCR), has become
      available. We have evaluated this technique, comparing the results with those
      previously obtained by SB in a group of patients suspected of having PWS or AS.
      PATIENTS AND METHODS: Genomic DNA from 70 patients with suspected PWS or AS was
      used. Methylation testing by SB was carried out using the probe PW71B labeled
      with radioactivity. For methylation testing by PCR the DNA was treated with
      sodium bisulphite and hydroquinone and PCR preformed using specific primers for
      the maternal and paternal alleles. RESULTS: Of the 70 patients studied by PCR, 45
      were normal, 17 and 8 showed altered molecular patterns that were compatible with
      PWS and AS, respectively. The concordance with the results obtained previously
      with SB was 100%. CONCLUSIONS: These data suggest that the reliability of this
      new technique is very good and it has advantages compared to SB, since it
      requires a smaller quantity of DNA and can be applied for diagnosis in newborns.

PMID- 9662841
TI  - [Relationship between lipoprotein A, apolipoprotein A and their isoforms in
      parents and children].
AB  - OBJECTIVE: It has been observed that the apo(a) isoforms of low molecular weight
      predict the family history of premature ECV. Our objective was to study the
      relationship between the levels of Lp(a) and the isoforms of apo(a) in parents
      and children. PATIENTS AND METHODS: Twenty-four families, where at least one of
      the children had been diagnosed with familial or polygenic hypercholesterolemia
      and at least one of these children and one parent had Lp(a) > or = 30 mg/dl, were
      studied. They were classified according to whether Lp(a) was > or = < 30 mg/dl,
      with 44 and 38 subjects in each group, respectively. The total cholesterol,
      triglycerides, HDL and LDL, the Lp(a) and apo(a) isoforms were determined, as
      well as the relative concentration of the latter. RESULTS: The molecular weight
      average of the major isoform was lower in the group with high Lp(a) levels (592
      +/- 38 vs 656 +/- 65 kD, p < 0.001). An inverse correlation between Lp(a) levels
      and the major isoform size was found (r = -0.522, p < 0.001). The correlation of
      the Lp(a) levels in the child with that of his or her "best fit" (the best fit
      parent was that whose level was closer to that of the child) was very significant
      (r = 0.61, p < 0.01), but lower than the corresponding paternal apo(a) isoform
      levels (r = 0.801, p < 0.01). The study of the apo(a) isoforms in parents and
      their children suggests not only that the isoform is inherited, but also its
      concentration. CONCLUSIONS: Subjects with small size apo(a) isoforms have higher
      Lp(a) levels. There is a better correlation between parents and children in the
      phenotypes of the apo(a) than in Lp(a) levels. The determination of these
      parameters allows the identification of a risk population.

PMID- 9662842
TI  - [Down's syndrome and leukemia].
AB  - OBJECTIVE: Children with Down's Syndrome (DS) have a high risk for leukemia and
      need special clinical management. For this reason we have reviewed our
      experience. PATIENTS AND METHODS: All children with DS diagnosed a having acute
      leukemia during a 21-year period were reviewed retrospectively. Treatment was
      administered according to current protocols in our unit at the time of diagnosis
      without any initial modification. RESULTS: There were 13 children with DS and
      acute leukemia [6 ALL, 4 AML and 3 transient leukemias (TL)]. No patient
      presented CNS leukemia at diagnosis. All children with AML and DS were under
      three years of age and standard treatments did not achieve satisfactory results.
      TL regressed in two newborns without developing AMKL later. Five out of six
      patients with DS and ALL achieved complete remission. Currently, 4 of these
      children are alive and off therapy. Toxicities related to treatment were observed
      in almost all of the patients. CONCLUSIONS: Children with DS suffer a higher risk
      of developing leukemia. They should receive standard protocols, but aggressive
      supportive care might be provided as they have a higher incidence of treatment
      related toxicities. Prognosis of these children is similar or even better in some
      cases than children without DS. TL is a true neoplastic process capable of
      spontaneous remission and it can progress to AMKL.

PMID- 9662843
TI  - [Analysis of preventive behavior for accidents among adolescents in our setting].
AB  - OBJECTIVE: Our objective was to analyze the preventative behavior for accidents
      in adolescents in our environment. PATIENTS AND METHODS: The accident
      preventative behavior of adolescents was studied by means of an anonymous
      questionnaire distributed to 268 students in a secondary school. A descriptive
      study regarding hazardous agents was conducted. We studied the relationships
      between the age, sex, number of siblings and the educational and economic level
      of the parents. RESULTS: Our study identifies deficiencies in the prevention of
      burns, traffic accidents and alcohol consumption. We detected the influence of
      age, sex, number of siblings and sociocultural level of the parents. CONCLUSIONS:
      The prevalence of a high risk attitude in adolescents suggests that appropriate
      counseling by pediatricians and appropriate prevention programs should be
      implemented.

PMID- 9662844
TI  - [Raynaud phenomenon in childhood: review and progress control in eight cases].
AB  - OBJECTIVE: The purpose of this study was to analyze the properties of Raynaud's
      phenomenon in childhood, as well as its evolution, pathology and differences with
      regard to adults. PATIENTS AND METHODS: The cases of patients affected by
      Raynaud's phenomenon between 1988 to 1996 in the pediatric rheumatology unit of
      Sant Joan de Deu in Barcelona have been reviewed. We evaluated the information
      regarding the clinical history and the complementary tests performed. RESULTS: We
      examined the results of eight cases affected by Raynaud's phenomenon. All of
      these were girls with an average age of 9 years and 9 months. The most typical
      clinical feature was sensitivity to cold. From an analytical point of view, 62.5%
      of the cases had positive antinuclear antibodies. Nail-fold capillary microscopy,
      which was carried out in all patients, was abnormal in six cases and had a
      "scleroderma-like" pattern in three of them. According to Le Roy-Medsger
      diagnostic criteria, we found one case (12.5%) of Raynaud's phenomenon classified
      as primary, five more (62.5%) as probably secondary to a connective tissue
      disease and two cases as secondary (25%, a sclerodermic and connective tissue
      disease). CONCLUSION: Raynaud's phenomenon could be the first symptom of a
      connective tissue disease, but in general there is a low prevalence in childhood.
      It is important to follow up these girls for a long period because of the high
      probability of developing a connective tissue disease. It is possible to do this
      thanks to anamnesy, clinical exploration, searching for antinuclear antibodies
      and nail-fold capillary microscopy.

PMID- 9662845
TI  - [Prevalence and severity of asthma in 13-14-year-old children in Bilbao].
AB  - OBJECTIVE: The objective of this study was to know the prevalence and severity of
      bronchial asthma in 13-14 year old children living in Bilbao, a seacoast
      industrial town in the North of Spain. PATIENTS AND METHODS: A sample of 13-14
      year old children living in Bilbao was studied. Random sampling amongst school
      centers was done. Fifty-eight centers were included and a total of 3,578 children
      between 13-14 years old were studied. The International Study of Asthma and
      allergy in Children (ISAAC) written and video questionnaires were used.
      Statistical analysis included bar diagrams, qualitative variable frequencies and
      the Chi 2 test to study the contrast and the association between variables. The
      statistical significance level was 95%. The relative risk according to sex was
      obtained. RESULTS: The questionnaires that were valid (3,213) represented 89% of
      the selected sample. The accumulated asthma prevalence was 18.9%. The actual
      asthma prevalence (asthma during the last year) was 11.9%. Severe asthma was
      present in 11.9% of the children. Asthma had been previously diagnosed in 16.3%
      of the children. The relative risk of being diagnosed was 1.39 for males.
      CONCLUSIONS: These figures are similar to those obtained in other populations
      with the same geographic and climate characteristics.

PMID- 9662846
TI  - [Amino acid changes in blood of children with severe liver disease. The
      evaluation of differences according to distinct physiopathology].
AB  - OBJECTIVE: The aim of this study was to know the serum amino acid profiles in
      children with terminal hepatic diseases and to assess the differences between the
      two main physiopathological groups of hepatic damage: cholestasis and cellular
      necrosis. PATIENTS AND METHODS: We studied twenty-six pediatric patients with
      severe hepatic diseases admitted to the Pediatric Intensive Care Unit. Patients
      were divided into two groups according to the predominant hepatic lesion:
      cellular damage (fourteen children) and cholestasis damage (twelve cases).
      RESULTS: Overall, there is a significant increase in the aromatic amino acids
      (AAA) phenylalanine (p < 0.04) and tyrosine (p < 0.0003) and a decrease in the
      branched-chain amino acids (BCAA) leucine, isoleucine and valine (p < 0.00001),
      with a reduction in the BCAA/AAA ratio (p < 0.00001). However, we found a
      significant decrease in glutamine, cysteine, taurine, serine, threonine,
      tryptophan, total amino acids and essential amino acids, together with higher
      levels of glutamic acid, ornithine and citrulline, which reflects a more complex
      metabolic disturbance. The group with cholestatic damage shows very low taurine
      levels (p < 0.0003). Patients with predominantly cellular damage have higher
      increases in tyrosine (p < 0.01), phenylalanine and hydroxyproline (p < 0.01).
      CONCLUSIONS: These findings may help us to better understand the complex
      physiopathology of amino acid metabolism in different liver diseases. Moreover,
      the extremely low levels of taurine found prompted us to recommend additional
      dietary support particularly in children with cholestatic hepatopathy.

PMID- 9662847
TI  - [Laparoscopic surgery in children].
AB  - OBJECTIVE: We summarize our experience in laparoscopic surgery between 1992 and
      1997 in an attempt to provide the pediatrician with up-dated information
      regarding the background, technical basis and limitations of this procedure in
      children. PATIENTS AND METHODS: For our 315 operations we used conventional
      endoscopic equipment with miniaturized instruments and regular anesthetic
      procedures assisted only with on-line capnography and increased tidal volume.
      Ages ranged between newborn and adolescence and the main indications for surgery
      were gonadal operations (n = 113), fundoplication (n = 40), cholecystectomy (n =
      35), exploration for recurrent abdominal pain (n = 44) and appendectomy (n = 29),
      but we also performed spleenectomies (n = 7), nephrectomies (n = 6),
      rectosigmoidectomies (n = 4) and several other procedures. RESULTS: Complications
      were scares [4 major (1.2% and 17 minor (5.3%)] and were satisfactorily solved.
      The conversion to an open operation was felt necessary in only 7 instances (2.2%)
      and this approach has been fully rewarding in terms of good results, little pain,
      short hospital stay and rapid recovery. CONCLUSIONS: Laparoscopic surgery is
      already a realistic alternative in pediatric medicine and its indications are
      growing every day as a result of its widespread use. The pediatrician has to be
      aware of the opportunity, rationale and limits of this approach since he will be
      increasingly confronted with it.

PMID- 9662848
TI  - [Eye injuries in childhood].
AB  - OBJECTIVE: The purpose of this study was to analyze the epidemiological, damage
      and preventative aspects of the pediatric ocular injuries treated during the last
      five years in our hospital. PATIENTS AND METHODS: We have revised all clinical
      histories of ocular injuries in the Emergency Services of the Asturias Central
      Hospital from January 1992 to December 1996. Two hundred fifty-seven cases were
      reviewed and the following parameters were studied: age, sex, kind of injury,
      causes and places where they originated, hospitalization or no, and functional
      sequeale. RESULTS: Eighty percent of the cases were male (206 patients). Most,
      85.6% (220 cases) did not require hospital attention, while hospitalization was
      necessary in 14.4% (37 cases). Concerning the latter, 73% (27 cases) were in the
      hospital less than 7 days, while the other 27% (10 cases) were hospitalized from
      8 to 14 days. As for the cause of and the location where the injuries took place,
      our results were as follows: school-home 33%, playtime-leisure 32%, sports
      accidents 12%, assaults 10%, traffic accidents 3% and unknown causes 10%. Minor
      injuries tend to imply the full restitution of sight (a large percentage were
      revised by their own ophthalmologist). Serious injuries caused the following
      functional losses: loss of eyeball in 2 cases (traffic accident), monolateral
      blindness in 2 cases serious amblyopia in 10 cases, and moderate amblyopia in 6
      cases. CONCLUSIONS: Males suffer injuries 4 times more frequently than females
      and these are very infrequent before the age of 3 years. Traffic accident
      injuries are rare in comparison to in adulthood. Important immediate visual
      sequale were seen in 7.8% of the cases, although these may also appear later in
      cases that at first present good function during the acute phase.

PMID- 9662849
TI  - [Kangaroo method in delivery room for full-term babies].
AB  - OBJECTIVE: Our objective was to determine the tolerance to kangaroo care in the
      delivery room. PATIENTS AND METHODS: We have studied 651 normal full term newborn
      infants delivered in our hospital during an 8 month period. Immediately after
      birth, the newborn infants were dried and placed in skin-to-skin contact between
      their mother's breasts. They remained in kangaroo care in the delivery room,
      during transportation to the post-partum area and in their room as long as two
      hours. The kangaroo care duration, the infant's post-kangaroo care axillary
      temperature, the mother's and infant's attitudes and the type of newborn feeding
      were recorded. RESULTS: Of the patients studied, 533 (82%) were put in skin-to
      skin contact and the kangaroo care lasted 49 +/- 23 min (mean +/- SD). Eighty
      percent of the mothers had decided previously to breastfeed their child. The post
      kangaroo care axillary temperature was > or = 36 degrees C in 96% of the newborns
      and it was proportional to the kangaroo care duration (r = 0.31, p < 0.0001; IC
      95%; beta = 0.0038-0.0068). During kangaroo care, most of the mothers looked at
      their child and were happy, although 21% felt tired. Almost all infants (98.5%)
      stayed awake. The newborn infants who spontaneously did the first breastfeeding
      during the skin-to-skin contact remained more time in kangaroo care (60 +/- 22 vs
      36 +/- 17 minutes; p < 0.0001). If the infant remained more than 50 minutes in
      kangaroo care, he had nearly 8 times more probability of breastfeeding
      spontaneously (odds ratio = 7.73; IC 95%: OR = 4.02-15.1). CONCLUSIONS: We
      recommend kangaroo care in the delivery room as a safe and well tolerated method
      for mothers and newborn infants which contributes to their well-being. In order
      to improve breastfeeding and the newborn's temperature, we recommend that the
      infant remains more than 50 minutes in kangaroo care.

PMID- 9662850
TI  - [Fraser syndrome: frequency in our environment and clinical-epidemiological
      aspects of a consecutive series of cases].
AB  - OBJECTIVE: Four major characteristics (cryptophthalmos, syndactyly, genital
      anomalies and affected siblings) and eight minor characteristics (alterations of
      the nose, ears, larynx, oral clefts, umbilical hernia, renal agenesis, skeletal
      anomalies and mental retardation) have been defined for the diagnosis of Fraser
      syndrome. The generally accepted criterion for the diagnosis is at least the
      presence of 2 major and one minor characteristic, or one major and four minor
      characteristics. The etiology of the syndrome is autosomal recessive and siblings
      are frequently affected. PATIENTS AND METHODS: We show the characteristics of the
      7 cases of Fraser syndrome identified in the consecutive series of 1,405,374
      liveborn infants and 9,042 stillborn children surveyed by the Spanish
      Collaborative Study of Congenital Malformations (ECEMC) between April 1976 and
      March 1997. RESULTS AND CONCLUSIONS: The minimal estimated frequency of Fraser
      syndrome is 0.43 per 100,000 liveborn infants and 11.06 per 100,000 stillbirths.
      As has been shown in other case studies, we have observed a wide clinical
      expression of this syndrome. At present it is possible to prenatally detect some
      of the characteristics of Fraser syndrome through ultrasound examination of eyes,
      digits and kidneys. Four out of the 7 cases we present here were gypsies and the
      frequency of the syndrome among liveborn gypsy infants is 129.3 times higher than
      among the non-gypsy population. Therefore, given that the frequency of the gene
      is higher in the gypsy population than in other ethic groups, it is recommended
      that a special search among gypsies for the identification of this and other
      autosomal recessive syndromes be performed.

PMID- 9662851
TI  - [Prospective study of Candida-related sepsis in the neonate].
AB  - OBJECTIVE: Our objective was to carry-out a prospective study of newborns with
      systemic candidiasis admitted to our Neonatology Unit in a teritiary hospital
      during the period of March 1994-September 1997. PATIENTS AND METHODS: To be
      included in the study the patient had to have Candida sp recovered from a
      normally sterile body fluid and clinical signs of sepsis. We analyzed perinatal
      and neonatal antecedents, risk factors, clinical course, diagnosis, treatment and
      outcome. RESULTS: The incidence of systemic candidiasis was 0.62% (14 newborns).
      Two were term infants and 12 preterm infants, 9 of which weighed less than 1500
      g. All of the patients had as predisposing factors the use of broad spectrum
      antibiotics, prolonged intravascular catheterization and parenteral nutrition,
      while 64% had mechanical ventilation. The mean age at onset of sepsis was 22
      days, with non-specific clinical presentation. Four infants were treated with
      intravenous amphotericin B and 9 with liposomal amphotericin B in association
      with fluconazole in one patient and with flucytosine and fluconazole in another.
      No adverse effects were observed. Mortality was 21%. C. parapsilosis was isolated
      in 7 cases and C. albicans in another 7 patients, with an important increase in
      C. parapsilosis in the last few years. CONCLUSIONS: Clinical suspicion of
      invasive candidiasis requires the removal of indwelling catheters and early
      initiation of systemic ungal therapy to reduce mortality. The increased incidence
      of species with more epidemic presentation like C. parapsilosis reinforce the
      importance of control measures such as handwashing for all personnel and aseptic
      management of intravascular catheters and solutions in order to prevent
      infections.

PMID- 9662852
TI  - [The importance of genetic diagnosis in an atypical case of spinal muscular
      atrophy type I].

PMID- 9662853
TI  - [Lethal ingestion of hydrogen peroxide].

PMID- 9662854
TI  - [Ring chromosome 14: report of a new case].

PMID- 9662855
TI  - [Vasculitis with severe lung involvement in a child: Henoch-Schonlein purpura or
      Wegener granulomatosis?].

PMID- 9662856
TI  - [Transient neonatal diabetes mellitus].

PMID- 9662857
TI  - [Acute pulmonary edema caused by laryngospasm following general anesthesia
      recovery].

PMID- 9662858
TI  - [What is the diagnosis? A 2-year-old child refuses to walk].

PMID- 9662859
TI  - [Cutaneous anthrax in a child].

PMID- 9662860
TI  - [Body piercing: a harmless fashion?].

PMID- 9662861
TI  - [Buttarelli syndrome].

PMID- 9662862
TI  - [Macrostomia secondary to transverse facial cleft of Tessier No.4].
AB  - A case of bilateral macrostomia type transverse facial cleft of Tessier n. 4 is
      reported, which was operated on with good results when had ten months of age,
      repaired using suture of three planes of three embryonic folds. A treatment plain
      precocious is recommended and pathogenic theories about this uncommon entity are
      exposed.

PMID- 9662863
TI  - [Primitive neuroectodermal tumors: difficult tumors versus modern oncology].
AB  - INTRODUCTION: Primitive peripheral neuroectodermal tumours (PNET) are rare masses
      and form part of the group of round small cell tumours which include a wide range
      of highly aggressive neoplasias such as Ewing's sarcoma, neuroblastoma, lymphoma
      and rhabdomyosarcoma. PNET present the same cell line as the tumours presented by
      F. Askin in 1979, both located in the thoracic-pulmonary region. MATERIAL AND
      METHODS: Of the last 26 thoracic neuroblastomas and 11 mediastinal-thoracic
      sarcomas treated at our centre, we observed 5 PNET in children with a mean age of
      12 years (range: 9-14 years). These patients presented a thoracic mass
      infiltrating sternum, clavicle, supraspinal muscle or, in two cases, a left
      lateral or paravertebral intrathoracic mass. The time elapsed between clinical
      observation and diagnosis was 6 weeks. Diagnosis was established by chest X-Ray,
      CT, bone scintigraphy, immunocytochemistry and cytology. Aggressive local
      treatment associated with stage IV SIOP chemotherapy for rhabdomyosarcoma was
      applied in all cases to prevent metastasis. RESULTS: Of the five PNET treated,
      one 16-year-old patient died (4 y 5 m post-diagnosis) from bone marrow
      infiltration which had evolved badly from the beginning. The remaining patients
      are disease-free. One patient who did not undergo surgery relapsed 1 year and the
      half after completing chemotherapy. He then underwent resection of the cranial
      portion of the sternum and substitution with iliac graft from the tissue bank.
      CONCLUSION: PNET manifest clearly some of the characteristics of current
      paediatric oncology. These tumours are easily misdiagnosed and at present may be
      differentiated by new diagnostic methods (immunohistochemistry, cytogenetics,
      hybridomas, molecular genetics), with the aim of selecting the most adequate
      treatment and consequently improving the prognosis of these aggressive embryonary
      tumours.

PMID- 9662864
TI  - [Skeletal muscle graft on the terminal ileum as a substitute for ileocecal valve:
      experimental study].
AB  - Behavior of a free skeletal muscle graft in contact with intestinal wall is
      analyzed in rats. On first phase, survival of the graft muscle in relation with
      previous denervation is studied. Nondenervated muscles suffer necrosis and
      fibrosis, whereas when denervated 4 weeks before grafting, the muscles are
      viable. On a second phase, the grafted muscle was studied on the long term. From
      8th post-transplant week on, the structural and metabolic features of the graft
      were similar to normal. On the third phase the efficacy of the muscle implant as
      a substitute of the ileocecal valve is checked. Germs on either side of the valve
      (ileum and cecum) are counted in normal rats, rats after valve excision and rats
      with substitution of the valve by a free skeletal muscle implant. There haven
      been significant differences between normal and no-valve rats (P < 0.001) and
      between no-valve and artificial valve rats (P < 0.005). There has not been
      significant difference between normal rats and artificial valve rats. We conclude
      that free skeletal muscle survives transplant to intestine, and it prevents
      bacterial reflux from colon to ileum.

PMID- 9662865
TI  - [Role of retrograde endoscopic dilatation with balloon and derivation using
      double pig-tail catheter as an initial treatment for vesico-ureteral junction
      stenosis in children].
AB  - The purpose of this project is to determine the role of the retrogade endoscopic
      dilatation with balloon and derivation using double pig-tail catheter, as inicial
      treatment for the vesicoureteral junction stenosis in children. As there are no
      previous paediatric publications, we present the technical details and early
      results. From August 1994 to December 1995, we have treated 11 children (8 boys
      and three girls), whose ages were between 4 months and eleven years, with
      objectivated vesicoureteral stenosis. Six of which were primary obstructive
      megaureters, and the other five were secondary obstructive megaureters (two were
      secondary to posterior urethral valves, one to neurogenic bladder, another one to
      ectopic ureter, and the last one was secondary to previous antirreflux surgery).
      We have used rigid dilatators and 7 Fr balloons over guide. All the patients have
      improved from their obstruction (proved by renogram). In six of the cases only
      one dilatation was needed, and in the other five only two dilatations. Only two
      patients presented reflux (grade I and IV). CONCLUSIONS: The endoscopic
      dilatation of the obstructive megaureter in children is possible, and reflux is
      rare.

PMID- 9662866
TI  - [Saliva in experimental gastroesophageal reflux].
AB  - Saliva, with a neutral pH, mucous content and inhibitory factors of the stomach
      acid secretion, can be considered a protecting element of the esophageal mucosa
      in the gastroesophageal reflux. 39 Wistar rats 175-225 g were used divided in
      seven groups: "C" control, "E-A" esophago-gastrostomy. "E-M" esophago-myectomy,
      "S-C" only sialoadenectomy, "S-EA" sialoadenectomy plus esophagogastrostomy, "S
      EM" sialoadenectomy plus esophago-myectomy. 15 days later the rats were
      sacrificed, the esophagus was taken out for its histological examination and
      blood samples were drawn. The comparison between the control and treated groups,
      showed a significant deterioration of the EA, SEA and SEM groups regarding the
      final weight, and the SC group in the white series and ions. Many of the animals
      with esophagus operations showed vomit signs and general affectation. None of the
      groups showed esophageal lesions in the histology, from which it can be deduced
      that, in the rat, a 90% saliva absence doesn't produce negative effects on the
      esophageal mucosa either in acid presence or not.

PMID- 9662867
TI  - [Effectiveness of audiovisual materials as a preparation for surgery in pediatric
      patients].
AB  - Research on paediatric surgical patients points to the urgent need to prepare
      them psychologically for hospitalization and surgery. In this respect, studies
      conducted outside Spain have shown that seeing a video on hospitalization and
      procedures for surgery is an effective technique for helping children and their
      parents to deal with this situation. The aim of the present work was to verify
      the effectiveness of this technique within the context of our hospitals. The
      results indicate that it is highly advisable to show such a video to patients and
      their parents before admission to hospital, since this: 1) clears up any doubts
      they might have; 2) gives a friendlier image of the hospital; 3) encourages
      parents to talk to their children; and 4) increases satisfaction among parents
      concerning the information they receive. One of the data which most clearly
      reflects the effectiveness of using the type of the audiovisual described is that
      98.2% of parents would recommend other families to see it.

PMID- 9662868
TI  - [Complicated liver hydatid: experience at one center].
AB  - The object of the present paper is to show four patients treated at the "Ricardo
      Gutierrez" Children's Hospital, with diagnosis of complicated liver hydatid
      disease, since april 1977 until january 1997. The four patients were previously
      healthy, and were admitted with acute symptomatology, which varied depending on
      the kind of complication. They were all studied before surgery, except for one
      patient, with simple x-ray, abdominal ultrasonography, and in some cases with
      computerized tomography; in addition blood serologic analysis were performed,
      which allowed us 100% effectiveness in the diagnosis. The observed complications
      were two intrabiliary rupture of the hydatid cyst, one infection of the cyst, and
      one intra abdominal rupture. All patients underwent surgery, which confirmed the
      diagnosis, and an uneventful follow up of 20 years in the first child. In spite
      of the infrequent presentation of the complicated hydatid disease, in an endemic
      region it is not impossible for it to be seen. In this case it will require a
      well trained team of specialists, to solve not only the problems that the
      diagnosis and treatment mean, but also the possibility of a correct follow-up,
      with the resolution of the possible obstacle that might show-up for the disease
      itself, and from the changes that the surgery produces.

PMID- 9662869
TI  - [Duodenal duplication].
AB  - Cystic duplication of the duodenum is a rare anomaly of the gastrointestinal
      tract. This is a report of a newborn with a cystic duplication of duodenum
      diagnosed prenatally. It's relevant the few clinical symptoms of a such big mass.
      The surgical procedure was excision of the cyst, with a good post operative
      curse.

PMID- 9662870
TI  - [Renal hydatid disease in childhood. Report of two cases].
AB  - Hydatid disease of the kidney is rare and is responsible for only 1-5% of all
      hydatid disease. Primary hepatorrenal association with hydatid disease is a 3%. A
      pre-operative diagnosis is often not considered because of the rarity of the
      disease and the infrequent occurrence of an isolated disease lesion of the
      kidney. These diagnosis may be mistaken for hepatic hydatid cyst. The accepted
      treatment is often the partial or total nephrectomy. We report two patients 4
      years-old, of both sexes. On admission, a palpable mass in the right upper
      quadrant of the abdomen is the only clinical sign. In the first case, the pre
      operative diagnosis was renal hydatid cyst and hepatorrenal hydatid disease in
      the second case. A patient who underwent at cyst enucleation only and total
      pericystectomy was performed in the other patient. The post-operatives courses
      were excellent in both patients. Total excision of the cyst and its adventitia
      with conservation of the renal parenchyma is the most desirable treatment, but
      it's not always feasible.

PMID- 9662871
TI  - An epidemiologic and entomologic investigation of a cluster of Rocky Mountain
      spotted fever cases in Delaware.
AB  - BACKGROUND: Rocky Mountain spotted fever (RMSF) continues to be the most common
      fatal tick-borne illness in the United States. In August of 1996, four children
      attending a summer camp in Delaware were diagnosed with RMSF. This report
      summarizes the results of the epidemiologic and entomologic investigation
      conducted by the Delaware Division of Public Health and the Centers for Disease
      Control and Prevention regarding this cluster of RMSF cases. Epidemiologic and
      clinical aspects of RMSF, as well as previously reported clusters of the disease,
      are also reviewed. METHODS: A questionnaire regarding symptoms and activities was
      administered via telephone to 163 (73 percent) of the 223 attendees. A suspected
      case was defined as an illness in a person attending the camp between August 11
      and 17 that occurred during the two-week period following the session,
      characterized by either 1) fever with one or more symptoms (i.e., headache, rash,
      myalgia, or fatigue) or 2) no fever with two or more symptoms. Cases of RMSF were
      confirmed by serologic evaluation. RESULTS: Seven of 13 patients with suspected
      RMSF submitted sera for testing. Four patients had confirmed RMSF; three were
      males, and the median age was 12.5 years compared with 12 years for all
      attendees. All confirmed patients reported fever, headache, fatigue, and rash. An
      increased risk of becoming ill was associated with overnight camping at site A
      (Odds Ratio (OR) undefined, p = 0.02), visiting or overnight camping at site B
      (OR undefined, p = 0.003 and 0.002), and leaving the trails when hiking (OR
      undefined, p = 0.02). CONCLUSIONS: These data suggest that development of RMSF
      was associated with visiting or camping at specific sites and behavior likely to
      increase contact with ticks. Camp supervisors were advised to educate campers
      regarding tick bite prevention measures, reduce underbrush around campsites, and
      encourage campers to remain on the trails. Health care providers should remain
      aware of the increased risk for RMSF during the spring, summer, and fall months.

PMID- 9662872
TI  - When should your asthmatic patients refill their MDI propelled with
      chlorofluorocarbons?
AB  - BACKGROUND: The United States Food and Drug Administration has changed its policy
      regarding product labeling of asthma MDIs. All asthma MDIs propelled by CFCs
      should be discarded at the discard point labeled on the canister and box. This
      policy is in transition with inconsistent product information given to patients
      and physicians. Previously, patients had been educated to replace the canister by
      observing its floating pattern in water. Now FDA labeling asks users to count the
      number of actuations. OBJECTIVE: To compare the discard point of sample and
      prescription-size Serevent (6.5 g and 13 g) and Vanceril 84 DS (5.4 g and 12.2 g)
      canisters to their floating pattern and total number of actuations in the
      canisters. DESIGN: Seven canisters each of Serevent 6.5 g and 13 g as well as
      Vanceril 84 DS 5.4 g and 12.2 g were shaken vigorously prior to actuation. One
      minute separated each actuation. The floating pattern was observed beginning at
      80 percent of the discard point. This was repeated to the last actuation of the
      canister. RESULTS: The floating pattern (tilt point) indicative to replace the
      Serevent 6.5 g and 13 g canisters as well as Vanceril 84 DS 5.4 g canister
      occurred after the discard point was reached. CONCLUSION: Floating patterns of
      the 6.5 g and 13 g Serevent inhaler as well as the 5.4 g Vanceril 84 DS do not
      assist the asthmatic patient in determining when to replace their canister.
      Because canisters have excess product and propellant beyond the labeled discard
      point, it may be possible for pharmaceutical companies to correlate the product's
      floating pattern to the drug concentration and particle size distribution up to
      and beyond the discard point. Through careful testing, floating patterns of MDIs
      may still be able to assist the asthmatic patient in determining when to discard
      the canister.

PMID- 9662873
TI  - NSAID use in populations at-risk for UGI hemorrhage.

PMID- 9662874
TI  - The unspoken affliction.

PMID- 9662875
TI  - Integrated management of childhood illness (IMCI) in the Americas.

PMID- 9662876
TI  - Chagas disease interruption of transmission in Uruguay.

PMID- 9662877
TI  - Growth retardation indicators in children under 5 years old.

PMID- 9662878
TI  - [Present-day organizational and legal construction of State sanitary and
      epidemiological services].

PMID- 9662879
TI  - [Comparative hygienic evaluation of nonionogenic surface-active agents with
      regard to stability and transformation].
AB  - The stability of the surfactants penazoline 10-16 B, neonol AF9-CN, and
      perfluorodecyl alcohol on boiling, exposure to ozone, ultraviolet and
      electromagnetic irradiation, biota in the model water reservoir, active sludge in
      the model air tank was evaluated. The transformation products forming under the
      influence of different damaging factors were assessed. The comparative hazard of
      parent compounds and their transformation products on biological test objects was
      studied.

PMID- 9662880
TI  - [Environmental pollution of some regions of the Ukraine by anionic surface-active
      agents].
AB  - Small rivers and soils in the North Ukraine were found to be polluted by anionic
      surfactants. The use of surfactant-based detergents makes the population complain
      of poorer health. Most of them mention the irritating effects of the detergents
      on the skin (65 and 30% in the urban and rural areas, respectively), upper airway
      (54 and 48%) and allergic reactions.

PMID- 9662881
TI  - [Sanitary-hygienic assessment of sludge utilization products].

PMID- 9662882
TI  - [Hygienic evaluation of microclimate in the high-speed electric locomotive cab].

PMID- 9662883
TI  - [Social-hygienic aspects of optimization of child nutrition in the Extreme
      North].
AB  - Children's nutrition in the Arctic areas is characterized by deficiencies of
      major nutrients and some groups of foodstuffs, among which there are lower
      dietary protein, fat, and vitamin intakes, shortage of meat, fish, dairy
      products, fresh vegetables and fruits. Based on the studies, the authors propose
      within the framework of the goal-oriented programme "Children of the North" their
      complex hygienic recommendations for optimization of nutrition and alimentary
      status of the Arctic children, involving some functional nutritional elements
      aimed at improving and promoting their health.

PMID- 9662884
TI  - [Prevention of health status impairment in children under conditions of the
      Extreme North].
AB  - Under the influence of climatic and geographic conditions of the Arctic, 7-9-year
      old children develop some functional tension, as evidenced by studies of their
      thermal reactions and cardiorespiratory system. Ethnic thermoregulatory features
      were found, which involved retained sensations of thermal comfort at lower skin
      temperatures and a higher gradient of skin temperatures in the trunk and
      extremities. In the morbidity pattern of young school-children, there is a
      prevalence of acute and chronic respiratory diseases whose major causes are
      cooling and recooling. The findings suggest that there is a causality of the
      children's health status and the environmental factors and show it necessary to
      develop scientifically substantiated preventive and conditioning measures to
      promote children's health.

PMID- 9662885
TI  - [Hygienic rationale for the allowable weight load of a daily training complex for
      schoolchildren].
AB  - Computed posturography (stabilography) was used to examine the locomotor function
      of 165 children from 1-11 forms under the influence of different real and model
      loads. Analysis of age-specific changes in their upright stability (by the data
      on the lateral velocity of the body's oscillations) yielded allowable load
      weights of a daily complete set for schoolchildren.

PMID- 9662886
TI  - [Chernobyl AES accident and health of the Tula Region population].

PMID- 9662887
TI  - [Radiation doses in the population of the coastal area of the Kakhovsk Water
      Reservoir].
AB  - The Chernobyl accident resulted in environmental radionuclide pollution in many
      areas, including the Dnepr river. The water and fish of the Kakhovsk Water
      Reservoir were under study and tested for 90Sr and 137Cs. It was found that the
      content of 137Cs achieved pre-accident levels and that of 90Sr was 4-6 times
      higher than that prior to the accident. The fish levels of the above
      radionuclides were 10-20 times as high as the pre-accident levels. Due to the
      consumption of fish, the radiation doses of the radionuclides, mainly 90Sr, in
      the population living in the costal areas of the Kakhovsk Water Reservoir were 20
      30 times higher than the pre-accident levels.

PMID- 9662888
TI  - [Effects of the surface of asbestos fiber on its biological aggressiveness].

PMID- 9662889
TI  - [Experimental assessment of the development of delayed-type hypersensitivity upon
      exposure to phenoxy herbicides].

PMID- 9662891
TI  - [Determination of total daily burden of surface-active agents on the human body].

PMID- 9662890
TI  - [Toxicological evaluation of romucide].

PMID- 9662892
TI  - [Prophylactic disinfection of railway stations and cars by using electrolytic
      sodium hypochlorite].

PMID- 9662893
TI  - [Environmental survival of Bacillus aeruginosus and changes in the structure of
      its population].

PMID- 9662894
TI  - [Sanitary-hygienic assessment of thermally-treated galvanic sludges in sewage
      plants].

PMID- 9662895
TI  - [Toxicologic-hygienic assessment of hydrolyzed rectified technical ethyl
      alcohol].

PMID- 9662896
TI  - [Experience in the use of a rapid bacterial analyzer REBIT in laboratories of
      sanitary and epidemiological services].

PMID- 9662897
TI  - [Some aspects of the impact of man-made environmental pollution on the
      population's health (review)].

PMID- 9662898
TI  - [Hygienic significance of environmental accumulation of dioxin (review)].

PMID- 9662899
TI  - [Solid waste and its effect on health (review)].

PMID- 9662900
TI  - [New regulations on state control of the use and preservation of water objects].

PMID- 9662901
TI  - [Experience with under-water birth].
AB  - Underwater birth is now deemed an acceptable type of delivery. Safety is a
      recurring consideration, the main concern being that of drowning. But in reports
      of 19,000 underwater births no untoward events were noted. Also, need for pain
      relief and of intervention during labor were both reduced. The short term
      indicators of neonatal outcome were good. A recent review explains 5 different
      physiological factors which inhibit initiation of fetal breathing under warm
      water. Many studies have shown no increase in risk of infection of either mother
      or baby. We report our experience with 26 women, 23 of whom actually delivered in
      the pool with excellent results. We believe that birth under water is safe and
      beneficial if done properly for low-risk patients.

PMID- 9662902
TI  - [Effects of vertical banded gastroplasty on weight, quality of life and
      nutrition].
AB  - We examined the long term results of vertical banded gastroplasty 3-10 years
      after operation. They were assessed by weight lost, incidence and severity of
      untoward effects and improvement in diet and in quality of life in 75 of 122 who
      had had the operation. Average weight lost was 28.5 +/- 14.9 kg (p < 0.001) in 5
      years and 58.6 +/- 30.4% of excess weight, which brought patients to within 32 +/
      25.2% of ideal weight. According to these measures, in 63-76% the operation had
      been successful in causing weight loss. The 2 criteria for successful weight loss
      were loss of more than 50% of weight in excess of ideal body weight and residual
      body weight less than 50% greater than ideal body weight. There was a greater
      risk of failure in unmarried subjects older than 45 (odds ratio for not losing
      weight was 6; in those weighing more than 120 kg it was 9). We saw evidence of
      this mostly 4 years after operation (odds ratio 11). The degree of success in
      weight loss was correlated with texture of food (softness) preferred and length
      of operation. Of those interviewed, only 65% were satisfied with their results.
      The greatest improvement in quality of life measurements was in physical
      activity, perception of health, and frequency of feeling depressed. Side-effects
      were vomiting, reflux and fatigue. Only 34.7% were able to digest solid foods, so
      that subjects are at risk for nutritional deficiencies.

PMID- 9662903
TI  - [Recurrent tuberculosis in a psychiatric hospital, recurrent outbreaks during
      1987-1996].
AB  - During 1987-1996, 39 of 720 patients hospitalized (most for severe schizophrenia)
      were diagnosed as having active pulmonary tuberculosis (5.4%, 975 per 105 per
      year). In 1992-1993, after a cluster of 5 cases was found, all patients were
      screened by PPD skin test and chest X-ray and 16 more cases were identified.
      Diagnosis was confirmed bacteriologically in only 10 of them but there were
      typical radiological findings in the others. 39 were treated with a multi-drug
      regimen. In addition, 333 exposed patients and 21% who had converted their skin
      tests were given isoniazid preventive therapy. A small increase in levels of
      liver enzymes was common, but significant abnormality (over 4 times the upper
      limit of normal) was found in only 7 patients, in whom therapy was therefore
      stopped or changed. During a follow-up period of 4 years, 2 more developed
      tuberculosis and 33 converted their PPD reactivity status. We conclude that an
      outbreak of tuberculosis in a psychiatric hospital can be controlled with a
      relatively low rate of side-effects by using systematic diagnostic and
      therapeutic measures. However, single step screening is not sufficient. Routine
      screening of all new patients, a high index of suspicion and contact
      investigation are needed.

PMID- 9662904
TI  - [Clinical characteristics of Crohn's disease in children and adults].
AB  - There are few reports contrasting the clinical characteristics of Crohn's disease
      in different age groups. We therefore compared retrospectively children and
      adults with Crohn's disease. 23 children (mean age: 12.8 +/- 2.5 years) and 66
      adults (mean age: 27.0 +/- 4.0 years) were studied. Presenting symptoms of
      abdominal pain and diarrhea were significantly more common in adults, while in
      children anorexia and weight loss were more frequent. Children tended to present
      with extra-gastrointestinal tract symptoms as well, mainly anemia and joint
      involvement. Common symptoms during active disease did not differ between groups,
      except that weight loss, evident in all children, was found in only 70% of
      adults. Anemia was present during active disease in all pediatric cases but in
      only 62% of adults. There were no significant differences between groups
      regarding disease location, gastrointestinal complications and extra-intestinal
      manifestations. We conclude that in children Crohn's disease may differ
      significantly, mainly presenting with nonclassical symptoms, such as anemia and
      joint involvement. The primary care physician should be aware of these
      differences.

PMID- 9662905
TI  - [Propofol anesthesia for craniotomy in patients who are awake].
AB  - During craniotomy, the patient's cooperation is needed during procedures in which
      continuous neurological examination and mapping of crucial regions close to the
      area to be resected area are required. We report our experience in 9 patients who
      underwent such procedures under intravenous propofol as the main sedating agent.
      This short-acting hypnotic was administered prior to and during the painful
      stages of the procedure. Patients were fully asleep when the skull was opened and
      the dural flap raised or excised. During the rest of the operation patients were
      lightly sedated but remained responsive and cooperative. This enabled precise
      intra-operative mapping of the brain and surgery-related neurological deficits
      were avoided. Respiratory depression or hemodynamic compromise were not
      encountered. All patients were comfortable during the operation and there were no
      additional neurological deficits after operation. We believe that propofol should
      be the main sedating agent used for these procedures.

PMID- 9662906
TI  - [Paroxysmal nocturnal hemoglobinuria].
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired disorder of blood
      cells which originate from an abnormal hematopoietic stem cell. The condition is
      characterized by nocturnal hemoglobinuria, chronic hemolytic anemia, and
      thrombosis. We describe a 60-year-old woman with PNH admitted with abdominal pain
      and jaundice, who had dark urine on arising after a night's sleep. The diagnosis
      was established by the typical clinical story and a positive Ham test. She was
      successfully treated with Halotestin and folic acid. Although PNH is rare, it
      should be considered in the differential diagnosis of hemolytic anemia. Early
      diagnosis and treatment are important.

PMID- 9662907
TI  - [Orthostatic hypotension as a manifestation of malignant lymphoproliferative
      disease].
AB  - An 85-year-old man was admitted with 6-month history of incapacitating
      orthostatic hypotension. Investigation led to the discovery of sympathetic
      dysautonomia, sensorimotor neuropathy and malignant lymphoproliferative disease.
      Several attempts to treat the orthostatic hypotension or the neoplastic disease
      failed to improve his condition. Orthostatic hypotension precipitated by
      sympathetic dysautonomia may be an infrequent effect of early malignant
      lymphoproliferative disease.

PMID- 9662908
TI  - [Epidermoid cyst of the spleen].
AB  - Splenic cysts are rarely found or diagnosed. Excluding cases of trauma, the
      events preceding their development have not been fully understood. We describe a
      22-year-old woman in her 34th week of pregnancy in whom ultrasound revealed a
      cystic lesion 8 x 10 cm. in diameter in the left upper abdomen. Further imaging
      tests followed by laparotomy confirmed the splenic origin of the cyst.
      Splenectomy was performed and the lesion was histopathologically defined as an
      epidermoid cyst.

PMID- 9662909
TI  - [The bitter taste of food safety].

PMID- 9662910
TI  - [New era in AIDS therapy with highly active anti-retroviral agents].

PMID- 9662911
TI  - [Clinical uses and recent developments of lasers in dermatology].

PMID- 9662912
TI  - [Function of maternal immune-system and the embryonic sensitivity to teratogens].

PMID- 9662913
TI  - [Polymorphisms of the renin-angiotensin system genes in progressive renal
      disease].

PMID- 9662914
TI  - [Infectious agents and atherosclerosis].

PMID- 9662915
TI  - [Should the calf veins be examined during ultrasonographic study of the legs in
      suspected deep vein thrombosis?].

PMID- 9662916
TI  - [Skeletal muscle damage syndrome due to overuse].

PMID- 9662917
TI  - [Psychiatric evaluation of heart transplant candidates].

PMID- 9662918
TI  - [Uterine sarcoma: a diagnostic and therapeutic challenge].

PMID- 9662919
TI  - [Single dose methotrexate for the treatment of ectopic pregnancy].

PMID- 9662920
TI  - [Correlation between success in specialty examinations and learning methods of
      family medicine residents].
AB  - Learning methods chosen by residents in family medicine during their residency
      and the correlation between them and achievement in the written specialty exams
      (Stage 1) were investigated. The learning patterns studied were: structured
      learning (certification course, study with a tutor, staff meetings, conferences)
      and self-learning (textbooks, journals, the Hebrew publication "Update," and
      audio tapes). Of 184 residents who took the examination in 1994-5. 104 responded
      to a questionnaire as to preferences for the various learning aids and
      satisfaction with their use. There was no correlation between use of a given
      learning method and success in the examination. Significantly more candidates
      preferred self-learning, especially among those who were successful, but also
      among some who failed the examination. There was no direct connection between the
      examination and the high level requirements of the residency program, for which
      up-to-date, integrated knowledge based on self-learning is needed.

PMID- 9662921
TI  - [Measuring temperature differences between the mouth and the rectum: a useless
      clinical procedure].

PMID- 9662922
TI  - [Early fixation of long bone fractures--the surgeon's perspective].

PMID- 9662923
TI  - [Centennial of Prof. Sussmann Muntner].

PMID- 9662924
TI  - [Dr. Chaim Israely and the Beer-Tuviya colony, 1929].

PMID- 9662925
TI  - [History of St. Petersburg I.I. Mechnikov State Medical Academy (former Sanitary
      Hygienic Medical Institute)].

PMID- 9662926
TI  - [Ways of optimization and problems of training in occupational pathology in a
      medical institute].
AB  - The article tackles up-to-date problems of higher medical education in Russia.
      The authors stress importance of wider education of attending doctors,
      occupational therapists and other professionals in occupational diseases, of
      increased number and duration of lectures and seminars on occupational diseases.

PMID- 9662927
TI  - [Use of geographic information systems in the evaluation of medical and
      ecological situation in a city].
AB  - Study using geoinformational technology provides integrity and compatibility of
      diverse information about territories, determines "cause-effect" relationships
      between environmental pollution parameters and some health state parameters.
      Intensive technogenic pollution with cadmium, zinc, mercury, copper, chromium,
      lead, benzpyrene, radionuclides could be assessed through data of ecologic and
      social hygienic monitoring and results of research works.

PMID- 9662928
TI  - [Method of determination of ecologically induced actual risk for human health and
      the degree of stress in medical and ecological situations].
AB  - Lipetsk town area was ranked according to maximal or minimal actual risk for
      public health (with consideration of medical and ecologic situation if influenced
      by technogenic hazards. That ranking enables to suggest municipal measures aimed
      at protection of population of ecologic hazards.

PMID- 9662929
TI  - [Problems of ecologic and hygienic safety of no-sewage and low-waste
      technologies].

PMID- 9662930
TI  - [Materials on clinical and functional examination of the respiratory system of
      workers exposed to dust].
AB  - Pulmonary diseases caused by dust occupy a leading place in occupational
      morbidity structure. Those diseases inspire much attention due to their high
      prevalence, especially in ecologically hazardous regions where the workers are
      under "double exposure". Upper respiratory tract diseases serve as a trigger for
      all respiratory disorders in workers exposed to dust. Early diagnosis of
      respiratory disorders includes history, clinical data, X-ray examination and
      assessment of pulmonary ventilation and together with concurrent cardiovascular
      diagnosis is necessary for well-justified prophylaxis.

PMID- 9662931
TI  - [Clinical and functional evaluation of health status of workers exposed to
      infrasound, noise and general vibration].
AB  - The article covers complex evaluation of health state in building industry
      workers engaged into ferro-concrete production in St. Petersburg. The health
      state was considered under combined action of infrasound, noise and general
      vibration. Clinical and functional evaluation included medical examination by
      doctors, blood biochemistry and CBC, ECG, computer integral rheography, voice
      audiometry. Data for 62 moulders helped to assess acoustic environment at
      workplace and to reveal the morbidity structure.

PMID- 9662932
TI  - [Study of mechanisms underlying the effects of low-frequency acoustic
      vibrations].
AB  - The article covers experimental data about influence of infrasound on hearing and
      vestibular apparatus, about body changes linked functionally to this apparatus.
      The authors revealed 4 zones of response of hearing and vestibular apparatus to
      infrasound. Infrasound appeared to affect directly nuclei of VIII and X cranial
      nerves and indirectly other organs and systems linked functionally to vagus
      nerve.

PMID- 9662933
TI  - [Methods of early diagnosis and prevention of occupational mercury poisoning].
AB  - At present advanced clinical manifestations of mercury intoxication are rare, so
      asymptomatic forms of the intoxication with nonspecific signs are prevalent.
      Complex evaluation of antioxidant and antitoxic systems in humans enabled to
      justify criteria for early diagnosis of mercury exposure and to elaborate
      therapeutic and prophylactic measures for the workers exposed.

PMID- 9662934
TI  - [Hygienic aspects of application of the resolution, "Certification of workplaces
      according to work conditions"].
AB  - The authors summarize experience of using "Act on procedure of working
      environment assessment at workplace". The authors analyze drawbacks of main
      documents used in assessment of working environment at workplace.

PMID- 9662935
TI  - [Work of Problem Training and Methodological Commission on occupational
      diseases].

PMID- 9662936
TI  - [Biological factor of work conditions in medical institutions and its influence
      on health status of medical personnel].
AB  - The article covers epidemiologic analysis of medical staff health state,
      epidemiologic evaluation of biologic factor's influence (degree and character of)
      on clinical staff, detection of principal risk factors for being infected. The
      aim is to create a supervision system and to elaborate effective measures for
      occupational risk prevention in medical personnel. Organizing a goal-seeking and
      effective system for occupational risk prevention and health care in medical
      staff, one should consider specificity in each medical establishment and in each
      occupational task.

PMID- 9662937
TI  - [Evaluation of cytogenetic activity in bone marrow cells exposed to infrasound
      (experimental data)].

PMID- 9662938
TI  - [Influence of work conditions on pregnancy, labor and health of newborn infants
      of female workers of match industry].

PMID- 9662939
TI  - [Responsibility for education and research. Opening address of the president of
      the 104th Congress of the German Society of Internal Medicine, Wiesbaden, 19
      April 1998].

PMID- 9662940
TI  - [Heparin-induced thrombocytopenia with unfractionated heparin. A prospective
      study of inpatient treatment of internal medicine patients].
AB  - AIM: To investigate the influence of unfractionated heparin on heparin-induced
      thrombocytopenia (HIT) type II. PATIENTS AND METHOD: In 162 patients with
      internal diseases treated therapeutically of prophylactically with unfractionated
      heparin (heparin sodium, heparin calcium), we carried out a prospective study to
      determine the incidence of HIT type I and II. 55.6% of the patients were female
      (n = 90) with an average age of 76.5 years (range: 25 to 96 years) and 44.4% male
      (n = 72) with an average age of 67.5 years (range: 17 to 93 years). A platelet
      count was taken regularly before the start of heparin treatment, on the first day
      of treatment and then every second day from day 5 to 20. Whenever HIT II was
      suspected, an HIPA test was performed. RESULT: Type I HIT occurred in 10%, type
      II in 3% of the cases. Two of the 5 patients with type II developed severe
      thrombotic complications. CONCLUSION: In view of the high incidence of HIT,
      regular platelet counts should always be carried out in patients receiving
      heparin treatment.

PMID- 9662941
TI  - [Renal iodine excretion by students in East Germany. A prospective study 1989 to
      1996].
AB  - AIM: A prospective longitudinal study was performed from 1989 to 1996 in order to
      check the effectiveness of prophylactic measures in Germany. TEST PERSONS AND
      METHODS: In 3 periods the urinary iodine excretion was examined in 1849
      adolescents from 2 regions (north, south) of former Eastern Germany. RESULTS: The
      consumption of iodized salt has increased substantially since 1994. This
      coincides with an increase in urinary iodine excretion. The median iodine
      excretion found in 1989/92 (n = 744) was 39.0 micrograms/g creatinine (4.7
      micrograms/dl), in 1994 (n = 123) 60.1 micrograms/g creatinine (6.0
      micrograms/dl), and in 1995/96 (n = 982) 101.1 micrograms/g creatinine (9.8
      micrograms/dl). However, the concentration was < 5.0 micrograms in 27.8% and <
      10.0 micrograms iodine/dl in 58.0%. Regional differences were not found.
      CONCLUSION: The iodine supply has been improved. However, the declared targets
      have not yet been met. The findings show that effective goitre prophylaxis can
      still be achieved while maintaining the voluntary principle.

PMID- 9662942
TI  - [Effect of pamidronate on clinical symptoms and bone metabolism in fibrous
      dysplasia and McCune-Albright syndrome].
AB  - BACKGROUND: Patients with fibrous dysplasia and the McCune-Albright syndrome
      which is characterized by additional endocrine dysfunctions, such as pubertas
      precox, suffer from a regional impairment in the differentiation of osteoblasts
      that is acquired during early embryogenesis and results in fibrous bone lesions.
      These lesions may cause bone deformities, fractures and chronical pain in the
      affected skeletal regions. We here report about our experience with a systemic
      treatment of the bisphosphonate pamidronate. PATIENTS: We treated 3 patients with
      fibrous dysplasia and 5 patients with McCune-Albright syndrome over a cumulative
      period of 37 patient-years. RESULTS: In all patients who suffered from painful
      lesions, intravenous infusions of 60 mg pamidronate resulted in an improvement of
      pain that lasted up to 6 months. In 2 patients we also observed a reduction in
      the size of some of the osteolytic lesions. Side effects were limited to
      asymptomatical fever and a small decline in total serum calcium within the
      physiological limits during the infusions. CONCLUSION: Pamidronate appears to be
      an effective and well tolerable treatment option for patients with fibrous
      dysplasia.

PMID- 9662943
TI  - [Disseminated infection with Mycobacterium avium complex (MAC) in HIV infection].
AB  - EPIDEMIOLOGY: Disseminated MAC-infection is one of the most frequent
      opportunistic infections occurring in HIV-infected patients. Severely
      immunocompromised patients with CD4-counts < 50/microliter are at greatest risk
      for the disease. Survival of untreated infection is very poor (5 to 6 months).
      With therapy survival is prolonged by about 4 months. CLINICAL PRESENTATION AND
      DIAGNOSTIC PROCEDURES: The leading symptom of MAC-infection is fever eventually
      accompanied by weight lost, night sweats, enlarged lymph nodes,
      hepatosplenomegaly, abdominal pain and anemia. Blood cultures are very sensitive
      and the most appropriate examination. Other diagnostic procedures include bone
      marrow cultures, biopsies of the gastrointestinal tract, lymph nodes and the
      liver. Detection of MAC in sputum and stool samples only proves colonisation but
      not dissemination. However, colonisation of the gastrointestinal tract frequently
      precedes disseminated disease. THERAPY: Combination of clarithromycin, rifabutin
      and ethambutol has proven to be the most efficacious therapy and therefore has to
      be considered as standard therapy for disseminted MAC-infection. Problems most
      frequently encountered with this medication include uveitis (rifabutin)
      gastrointestinal disturbances (clarithromycin) and leucopenia (rifabutin) as well
      as drug interactions with protease-inhibitors (rifabutin). PROPHYLAXIS:
      Clarithromycin, rifabutin and azithromycin given as primary prophylaxis can
      diminish the risk of disseminated MAC-infection. Although a survival benefit has
      been seen with clarithromycin, primary prophylaxis of MAC-infection is not
      standard care in many centers. Reasons to withhold MAC-prophylaxis include lower
      incidence rates in some countries as well as possible side effects and drug
      interactions. CONCLUSION: Disseminated MAC-infection is a frequent opportunistic
      disease in HIV-infected persons who are severely immunocompromised. Antibiotic
      combination therapy with clarithromycin, rifabutin and ethambutol improves
      clinical symptoms and survival. Primary prophylaxis with different regimens is
      efficacious but the specific epidemiologic situation in each country has to be
      considered.

PMID- 9662944
TI  - [Endocrine orbitopathy 1998].
AB  - BACKGROUND: Ophthalmopathy is the most common extrathyroidal manifestation of
      Graves' disease, also called thyroid-associated ophthalmopathy. CLINICS: This
      autoimmune disorder is characterized by a lymphocyte infiltration of the
      retrobulbar space. Activated T cells react with the target organ and secrete
      cytokines, leading to accumulation of glycosaminoglycans, interstitial edema of
      the peri- and retrobulbar tissue and enlargement of the extraocular muscles.
      During the inflammatory stage, the increased orbital pressure results in the
      clinical manifestation of the eye disease. DIAGNOSIS AND TREATMENT: Thus,
      therapeutic immunosuppression is often used initially, and by suppressing
      inflammatory changes, it can result in subjective and objective improvement of
      the thyroid eye disease. In recent years, new pathogenetic aspects and clinical
      randomized trials led to modified therapy concepts. CONCLUSION: Interdisciplinary
      management is recommended for rapid diagnosis and effective therapy of patients
      with thyroid-associated ophthalmopathy.

PMID- 9662945
TI  - [Diagnostic pitfalls in sulfonylurea-induced neuroglycopenic syndrome with
      hemiparesis, dysphasia and somnolence].
AB  - BACKGROUND: The neuroglycopenic syndrome, which is often due to sulfonylurea
      induced hypoglycemia, is frequently overlooked or misinterpretated as cerebral
      ischemia. PATIENTS: Two women aged 81 and 83 years, respectively, with type II
      diabetes treated with sulfonylureas presented with hemiparesis, dysphasia and
      somnolence. Both, general practitioner and emergency room physician first
      interpretated the symptoms as clinical signs of stroke without determination of
      blood glucose. After hours of delay due to unnecessary and expensive examinations
      including cerebral computed tomography the correct diagnosis of hypoglycemia was
      finally made. After injection of i.v. glucose the symptomatology was completely
      reversible. CONCLUSION: In every case of disturbance of consciousness, acute
      neurologic deficits and psychiatric abnormalities an immediate blood glucose test
      should be performed to exclude hypoglycemia.

PMID- 9662946
TI  - [Unilateral sacroiliac joint fusion].

PMID- 9662947
TI  - [Hepatitis B--diagnosis and therapy].

PMID- 9662948
TI  - [Basic medical competence: a neglected educational goal in medical education?].
AB  - This paper analyses some recent proposals of how to change undergraduate medical
      education in Germany and in other countries. This leads to the formulation of a
      set of fundamental clinical competencies, which are defined as skills that enable
      physicians to react to challenges pertaining to their work in a professional way.
      These fundamental clinical competencies comprise knowledge, skills and attitudes.
      With regard to the actual performance of the German system of undergraduate
      medical education, deficits are depicted in the following areas: psychosocial and
      communicative competencies including advice and provision of information to
      patients, primary care, public health, ethics and clinical epidemiology/evidence
      based medicine. For each of these areas, a proposal for change is provided.

PMID- 9662949
TI  - [Analysis of the cost of illness in backache].
AB  - BACKGROUND: Back pain has become quite a health problem in today's modern
      industrial society. Even though an excellent network of doctors and efficient
      treatments is available and most of the patients need only a few treatments, back
      pain is a common cause of illness and inability to work. This amounts to a
      considerable reduction in quality of life for those affected, additionally this
      also leads to a high economic burden for the national economy and the solidarity
      of the insured. COST ANALYSIS: The total costs caused by back pain come up to
      about 34 billion DM per year according to the present study. Ten billion DM of
      these amount to direct costs, which are divided into costs for physician visits
      (including diagnostic procedures) at about 35%, hospital, treatment at about 22%,
      rehabilitation at about 21%, physical therapy at about 17% and medication at
      about 5%. Regarding total costs, which are composed of around 70% indirect costs,
      the direct costs relativize immensly. CONCLUSION: Savings through restrictive
      prescriptions for medications therefore have no great impact on total costs. Only
      a more efficient therapy, which reduces sick days, number of recurrences and
      development of chronic illness as well as a more effective prevention, is able to
      limit the costs of back pain in the long-run. Therefore, more research on a
      broader base may result in a significant benefit in this area.

PMID- 9662950
TI  - [Electronic edition of SENPE (Spanish Society for Parenteral and Enteral
      Nutrition)].

PMID- 9662951
TI  - [Iron supplementation during pregnancy. Standards and alternatives].
AB  - The requirements of iron during gestation are very high and it is difficult to
      meet them, especially in women who go into a pregnancy with an exhausted storage
      of the mineral. In industrialized societies there is controversy regarding the
      usefulness or lack of supplementation. In some cases one recommends a routine
      iron supplementation during the second half of the pregnancy, in order to improve
      the situation of all women. Another tendency, keeping in mind the increased
      capacity for absorption seen during the gestation, is the selective
      supplementation of iron only after assessing the situation of the pregnant woman.
      A third alternative that may be useful in the future is that of monitoring the
      iron status (during the pregnancy and during the entire fertile period of the
      entire female population), increasing the consumption of foods that are rich in
      iron (meat, fish, fortified cereals), improving the bioavailability of the
      ingested iron (drinking orange juice with the meal or eating meat), and using
      weekly supplements of iron rather than daily supplements, as the former type of
      supplementation has an effect that is similar to that seen with a daily
      supplementation, and lacks many of the side effects of this (noncompliance with
      the standard, gastrointestinal trouble, decreased absorption of other nutrients).

PMID- 9662952
TI  - [Description and evaluation of the adequacy of parenteral nutrition in our
      hospital].
AB  - INTRODUCTION: Parenteral nutrition (PN) is a form of nutrition that can be very
      beneficial, but it does have some indications and complications that should be
      taken into consideration. With this work we would like to describe the
      characteristics of our patients with PN, as well as their follow up, and to
      evaluate the appropriateness of its prescription. MATERIAL AND METHODS:
      Retrospective study carried out at a hospital with 415 beds. All patients who
      received PN during the first six months of 1996 were reviewed. Inadequacy
      criteria are established and a nutritional assessment was carried out by means of
      clinical and analytical parameters. Catheter infections were recorded according
      to specific criteria and the clinical and analytical evolution of the patients
      was followed. RESULTS: A total of 83 patients were given parenteral nutrition.
      The most frequent indication was prolonged fasting after a surgical resection of
      the digestive apparatus. The most common nutritional status when beginning the PN
      was severe protein malnutrition (23%). There were 33 cases (39.7%) of PN that was
      not indicated and/or potentially avoidable. A catheter infection was reported in
      7 cases (8.4%).

PMID- 9662953
TI  - [Effect on viscosity and yield value of addition of different vegetable fat
      sources used in chocolate].
AB  - Viscosity and Yield Value of Casson are two chocolate properties. They are very
      important in the technological processes and they affect to the final product
      acepptation. In this study viscosity, yield value and fatty acid composition were
      determined of chocolates elaborated with different fat sources. A correlation
      study was made between these three variables. Viscosity and yield value were
      calculated with the Casson's education using a viscometer brookfield and fatty
      acids composition by gas-chromatography. Positive correlations between viscosity
      and yield value with stearic and palmitic acids contents have been found.
      Negative correlations between yield value and lauric content and viscosity and
      oleic acid content have been observed. The viscosity variations were relationed
      with total content of cocoa butter of different chocolates.

PMID- 9662954
TI  - [In-hospital malnutrition: indications of postoperative evolution].
AB  - A significant percentage of the patients admitted to our hospitals show signs of
      malnutrition that are neither detected nor treated and often become more severe
      during the hospital stay. This malnutrition can contribute to the loss of some
      important functions as, for instance the capacity for immune response and
      healing. In this study we use several simple, economical parameters to evaluate
      the nutritional status upon admittance and upon leaving the hospital of all the
      patients who in the course of a year occupied four randomly chosen beds in a
      general surgery ward at a county hospital in the Valencian Community. The results
      show that hospitalization reduced the number of over weight patients, duplicated
      the number of hypoalbuminemics and triplicated the number of people with body
      weight and body mass index (BMI) below normal levels. In patients over 40
      hospitalization decrease the values of all the parameters studied, whereas in
      younger subjects only the weight, the BMI and serum albumin values were affected.
      Fifty seven percent of the patients suffer some kind of postoperative
      complication and this incidence is higher among patients with malnutrition upon
      admittance. The most common complication is the nosocomial pneumonia and urine
      infection. The nutritional parameters that best predict possible postoperative
      complications are low values of serum albumin, total lymphocyte count, tricipital
      fat skin fold and arm circumference. In general, postoperative complications show
      only a slight positive correlation with the length of the hospital stay, but the
      longer the stay is the worst the nutritional status becomes.

PMID- 9662955
TI  - [Nitrogen balance in adolescent patients with chronic renal insufficiency].
AB  - Protein restriction in patients with chronic renal failure may be potentially
      beneficial, however the dangers in growing children of such restrictions must be
      considered. We analyzed the nitrogen balance in 60 chronic renal failure children
      (47 male y 13 female) Group A: 36 preadolescents. GFR was 54.5 +/- 25.6
      ml/min/1.73 m2. Group B: 24 adolescents. GFR 52.7 +/- 25.4 ml/min/1.73 m2.
      RESULTS: 55% of patients had a negative balance. 72% preadolescents and 17% of
      adolescents had positive nitrogen balance A good correlation was found between
      the range of energy and protein intake and nitrogen balance. CONCLUSIONS: 1. A
      good correlation was found between nitrogen balance and the range of energy and
      protein intake but no correlation with the renal function degree. 2. Adolescents
      had nitrogen balance negative. 3. It is necessary turn-over protein studies in
      this patients to know the requirements in children with chronic renal failure.

PMID- 9662956
TI  - [Artificial nutrition in the home. 1995 yearly report. NADYA-SENPE Group
      (Natiional Registry of Patient-Spanish Society for Parnteral and Enterlal
      Nutrition].
AB  - By means of a simplified questionnaire, the NADYA group has gathered and analyzed
      data with regard to the age, sex, diagnosis, access route, duration, form of
      administration, complications, and quality of life, in 812 patients (62% male;
      37% female) with At Home Enteral Nutrition (AHEN), and 19 patients (42% male; 57%
      female) with At Home Parenteral Nutrition (AHPN) corresponding the National
      Registry of 1995. The most frequent indication of AHEN was a neoplasm (41%),
      followed by neurological alterations (33%). The most common access route is the
      NGT (37%) followed by oral administration in 37%, PEG in 13% and surgical
      ostomics in 8%. The mean treatment time is 8 months. The index of
      complications/patient-year is 0.50 (gasterointestinal 0.17, and mechanical
      alterations 0.9). At the end of the study, 63% of the patients continued to
      receive AHEN, showing a mortality rate of 70%. The majority of the patients
      undergoing treatment presented a sever social disability (20%) or were bed ridden
      (18%). The most common indications for the AHPN are: radical enteritis (26%),
      Crohn's disease (21%), and mesenteric ischemia (16%). AIDS, motility alterations,
      and neoplasic diseases are scantly represented (10%). Tunneled catheters are used
      in 58% of the cases, and Port-a-Cath in 31%). The mean duration for the treatment
      was 7.9 months. An index of 0.47 hospitalization/patient-year was seen in
      relation to the nutritional treatment (mainly due to catheter septicemia). A
      mortality of 16% is noted, and 21% show a recovery of the oral route. 42% of the
      patients did not present an assessable social disability.

PMID- 9662957
TI  - [Quality of support by artificial nutrition: difficulties with AIDS patients].
AB  - The use of Enteral Nutrition (EN) in patients with AIDS with a severe nutritional
      deterioration, is the most common route, not only because of the risk/benefit
      relation, bur also because this is a physiological route that is easily managed
      and is profitable in terms of renutrition. However, and given the characteristics
      of the affected population, whose origin in a large percentage is the addiction
      to parenteral drugs, implanting this route in these patients is a challenge, as
      these patients refuse in more than 50% of the cases. Moreover, the risk group is
      not only a factor in the difficulty for applying the ideal across route, but also
      the combination of other elements like sex or the disease itself, force the
      clinical to use more aggressive methods (Parenteral Nutrition) or those that are
      less profitable nutritionally (Supplements). The negative aspects with regard to
      tube feeding of these patients are shown, in relation to the factors, and these
      are compared with the negative aspects of other diagnosis groups (rest of the
      Hospital).

PMID- 9662958
TI  - [Assessment of various anthropologic methods for estimation of the height of
      persons over 65 years of age].
AB  - The height measurement of people older than 65 years of age is limited in may
      cases by alterations of the vertebral column, which is why the determination of
      the body mass index for the evaluation of the nutritional status may be very
      imprecise. Formulae have been developed based on the height of the knee or the
      distance between the knee and the external malleolus, for estimating the height.
      With this study we wish to contrast the estimated height using these formulae
      with the height obtained in standing people older than 65 years of age. We
      studied a total of 202 patients, assessing the height based on the different
      methods of estimation, as well as using the body mass index. When analyzing the
      results, we found that there were no significant differences between the average
      height estimated from the height of the knee or the distance from the knee to the
      malleolus, and the average height obtained by diet measurement, and that the
      height estimated from the height of the knee has a greater average relative error
      (0.43) than the height estimated using the knee to malleolus distance (0.08). The
      obtained results show us that the height assessment of people older than 65 years
      of age should always take place by measuring them while standing, and in those
      subjects in whom this is not possible, the height will be estimated using one of
      the two formulae, as both are useful in our environment, although we recommended
      using the estimate based on the knee malleolus distance as this is simpler.

PMID- 9662959
TI  - Infection by Cryptosporidium parvum in renal patients submitted to renal
      transplant or hemodialysis.
AB  - The frequency of infection by Cryptosporidium parvum was determined in two groups
      of renal patients submitted to immunosuppression. One group consisted of 23 renal
      transplanted individuals, and the other consisted of 32 patients with chronic
      renal insufficiency, periodically submitted to hemodialysis. A third group of 27
      patients with systemic arterial hypertension, not immunosuppressed, was used as
      control. During a period of 18 months all the patients were submitted to faecal
      examination to detect C. parvum oocysts, for a total of 1 to 6 tests per patient.
      The results showed frequencies of C. parvum infection of 34.8%, 25% and 17.4%,
      respectively, for the renal transplanted group, the patients submitted to
      hemodialysis and the control group. Statistical analysis showed no significant
      differences among the three groups even though the frequency of C. parvum
      infection was higher in the transplanted group. However, when the number of fecal
      samples containing C. parvum oocysts was taken in account, a significantly higher
      frequency was found in the renal transplanted group.

PMID- 9662960
TI  - [Sandflies (Diptera, Psychodidae) from the transmission area for American
      cutaneous leishmaniasis in the town of Itupeva, the southeastern region of Sao
      Paulo state, Brazil].
AB  - The present study was effected aiming the verification of the seasonal, spatial
      and hourly of the phlebotominic species found in the county of Itupeva. Captures
      were performed fortnightly and 864 sand flies were collected between april/94 and
      march/95. 81.3% of the captured specimens belonged to 4 species: L. migonei
      (32.4%), L. whitmani (26.0%), L. intermedia (12.0%) e L. fischeri (10.9%). Such
      species showed larger densities during the cold and dry season of the year (from
      april to september/94) and were more active between the second and the fifth hour
      after twilight. L. migonei predominated almost in all the investigated
      surroundings being followed by L. whitmani and L. longipalpis in the domestic
      environments. In conclusion it is thought that in conjunction with L. intermedia,
      a suspect vector in the State of Sao Paulo, L. migonei and L. whitmani may have
      an important role in the transmission of cutaneous leishmaniasis in the area
      under study.

PMID- 9662961
TI  - Seroprevalence and sociocultural conditionants of Chagas disease in school-aged
      children of marginal zones of Asuncion.
AB  - Chagas disease is becoming a public health problem in Latin America due to the
      wide distribution, the high prevalence, the magnitude of the damage caused and
      the difficulties to control it. In Paraguay, the disease is mainly distributed in
      the departments of Paraguari, Cordillera and Central. Prevalence in marginal
      zones, where migrations from rural populations and endemic areas make possible
      the urbanization of the disease, has no been studied yet. This is a descriptive
      study with a cross-sectional sampling and a probabilistic system recruitment
      carried out in school aged children from marginal zones of Asuncion to determine
      the prevalence of Chagas' disease. Serological methods, parasite isolation and
      questionnaires were used to achieve the goals. Nine hundred and fifty three
      children were studied to determine the prevalence of Chagas' disease in marginal
      zones which was 1.4%.

PMID- 9662962
TI  - [American cutaneous leishmaniasis: sandflies from the transmission area in the
      town of Teodoro Sampaio, the southeastern region of Sao Paulo state, Brazil].
AB  - Sandflies were captured in a secondary forest zone in the county of Teodoro
      Sampaio, Sao Paulo, during 12 months as from May 1994. Two houses located
      respectively at 240 m and 850 m from the semi-deciduous forest were selected.
      Night Center of Disease Control trap captures were performed fortnightly from
      twilight to dawn intradomiciliarily, in the edge and the interior of the forest
      and in the peridomicile of each one of the houses. Captures were realized as well
      in the peridomicile using Shannon traps during 6 hour for 24 captures and 4
      quarter captures from twilight to dawn. The dominant species was Lutzomyia
      intermedia (93.5%). A larger number of insects were captured in the traps located
      in the edge of the forest. In the peridomicile of both houses an equivalent
      number of insects were captured, although a clear predominance of males was
      observed in the more distant located house. In the interior of the house located
      near the forest a larger number of specimens predominantly female were captured.
      L. intermedia and L. whitmani peaks occurred in the first hour and were
      characteristically more abundant in May, September and December when the mean
      temperature varied from 21 to 25.7 degrees C and the pluviometric index as from
      66.7 to 195.1 mm.

PMID- 9662963
TI  - [Observations on oviposition, hatching and the life span of Triatoma
      matogrossensis Leite & Barbosa, 1953 (Hemiptera, Reduviidae) as a function of
      their feeding on pigeons and rabbits].
AB  - A laboratory study was carried out concerning the influence of two kinds of blood
      meal on egg laying, egg hatching and life span of Triatoma matogrossensis. 68
      couples in 4 different groups with 20, 12, 20 and 16 individuals of each sex per
      group were formed. Maintained under laboratory conditions groups A1 and A2 were
      fed on pigeons and groups C1 and C2 were fed on rabbits. In relation to egg
      laying the best results were found in group A1. No differences on egg hatching
      were found between the groups fed on rabbits and those fed on pigeons. Concerning
      the life span, no differences between males and females in the 4 groups were
      observed but group A1 presented the longest life span and group C2 the shortest.

PMID- 9662964
TI  - Effect of a booster-dose of rabies vaccine on the duration of virus neutralizing
      antibody titers in bovines.
AB  - Humoral immune response using inactivated rabies vaccine was studied in 35 nelore
      cross-bred bovines of western region of Sao Paulo state. Ninety days after
      vaccination, 13 (92.8%) animals presented titers > or = 0.5 IU/ml, through mouse
      neutralization test. After 180 days, 9 (64.3%) sera showed titers > or = 0.5
      IU/ml, after 270 days, only one (7.1%) showed a titer of 0.51 IU/ml, and after
      360 days, all animals showed titers < 0.5 IU/ml. Group of animals receiving
      booster dose 30 days after vaccination presented, two months after, all with
      titers > 0.5 IU/ml. At 180 days, 17 (80.9%) sera presented titers > 0.5 IU/ml; at
      270 days, 15 (71.4%), with titers > or = 0.5 IU/ml and at 360 days, 4 (19.0%),
      with titers > or = 0.5 IU/ml. Booster-dose ensured high levels of neutralizing
      antibodies for at least three months, and 240 days after revaccination, 71.4% of
      animals were found with titers > or = 0.5 IU/ml.

PMID- 9662965
TI  - [The control of the transmission by transfusion of Chagas' disease in the
      Southern Cone Initiative].
AB  - The Southern Cone Initiative against Chagas' disease, was launched in 1991. The
      aim was to interrupt the transmission of Chagas disease by elimination of
      domestic populations of the major vector, Triatoma infestans, and by improved
      screening of blood donors. As a result of these activities, a marked reduction in
      the risk of transfusional transmission can now be seen throughout the programme
      area. In addition to specific legislation concerning the quality of transfused
      blood, a series of national and regional reference laboratories have been set up
      with the help of PAHO in order to improve the quality of pre-transfusional
      serodiagnosis. Results indicate a progressive reduction in the overall infection
      prevalence of blood donors, and show that the age-prevalence curve has shifted
      towards older age-groups. In this paper we analyse the changes in infection
      prevalence in the Southern Cone countries, drawing attention to the situation in
      Bolivia which has the highest indices of infection and lowest levels of coverage
      by the control programme. In this situation chemoprophylaxis of blood prior to
      transfusion may be recommended in accordance with PAHO criteria. In the medium
      term however, interruption of human Chagas disease transmission may be expected
      over most of the Southern Cone region, as long as the control activities are
      continued and consolidated through effective epidemiological surveillance.

PMID- 9662966
TI  - [Hanseniasis virchowiana in Chagas cardiopathy: an autopsy report].
AB  - This is a case report of lepromatous infection diagnosed at necropsy, with
      cardiac alterations directly caused by mycobacteria, in a 34-year-old black male
      with the cardiac form of Chagas' disease. The possible role of inflammatory
      mediators on cardiac dysfunction, and the possibility that immune depression may
      be due to factors associated with heart failure, as congestive splenomegaly and
      splenic infarctions, are emphasized.

PMID- 9662967
TI  - [HTLV-I/II seroprevalence in Gay men and female sex workers on Margarita Island,
      Venezuela].
AB  - In attention to the important HIV-1 seroprevalence observed in Margarita Island,
      we carried out this study to establish HTLV-I/II seroprevalence into target
      groups for sexual transmission. Therefore the survey was done with 141 female sex
      workers and 40 Gay men between 1994 and 1997. We found HTLV-I infection in one
      man. This is the first known report to describe epidemiological features of HTLV
      I/II infection in Margarita Island.

PMID- 9662968
TI  - [Emergencies in nasal and paranasal sinus diseases].
AB  - The paper provides statistical data obtained on 1126 patients with urgent nasal
      and paranasal sinus pathology of a total of 2054 patients urgently hospitalized
      to the ENT clinic of the Moscow Medical University in 1995. A detailed analysis
      is given of the incidence, diagnostic and therapeutic policy, complications in
      all kinds of nasal bleeding, acute and chronic sinusitis, trauma of the nose and
      paranasal sinuses, nasal furuncle.

PMID- 9662969
TI  - [Hearing loss correction by endogenous opioid stimulation].
AB  - Radioimmunoassay of beta-endorphine (RIA) in plasma was performed in patients
      with acute, subacute and chronic neurosensory hypoacusis. The RIA and
      audiological examination were made before treatment and after combined therapy
      consisting of pharmacopuncture and following low-frequency electrostimulation
      using negative polarity current. The above treatment elevated beta-endorphine
      levels in blood plasma. Positive results of the treatment correlated with
      elevated beta-endorphine levels in the end of the treatment.

PMID- 9662970
TI  - [The impact of electrical stimulation on the functional status of cochlear
      nervous structures in cats with experimentally induced hearing disorders].
AB  - Effects of non-invasive electric stimulation on hearing were studied in cats with
      depressed periphery of the acoustic analyser. Experimental neurosensory
      hypoacusis was induced by large doses of canamycin (25-30 mg/kg). The hearing was
      assessed by short-latent stem and cortical long-latent evoked potentials (EP).
      Consideration was also given to changes in the amplitude of the wave V of short
      latent EP in varying intensity of the sound stimulus. When deep suppression was
      reached, 8-day course of electric stimulation was started with registration of
      EP. It was found that canamycin elevates thresholds of identification of wave V
      of short-latent stem EP and thresholds of emergence of long-latent stem EP. The
      curve amplitude/intensity was also affected. The course of electrical stimulation
      returned the above parameters of the thresholds and the curve to the baseline
      levels. This is the evidence of therapeutic action of non-invasive electrical
      stimulation.

PMID- 9662971
TI  - [The dynamics of two-layer graft acoustic properties at different times after
      myringoplasty].
AB  - A two-year follow-up tympanometric results have been analysed for 40 patients
      subjected to myringoplasty. Ultrathin allocartilage was used as one of the
      transplant components. The static compliance of the neotympanic membrane seemed
      to change in a wide range, but the changes did not affect hearing. The formation
      of an adequate neotympanic membrane takes place by the end of the second year
      after the operation.

PMID- 9662972
TI  - [A comparative study of intoxication severity in patients with acute purulent
      otitis media].
AB  - Plasma levels of medium molecular peptides (MMP) were measured and Paramecium
      test was made in 28 patients with acute otitis media purulenta (AOMP). Of these,
      18 patients had complicating mastoiditis. The baseline results of both tests
      correlated with clinical symptoms of systemic endogenic intoxication. Paramecium
      test returned to normal after one day of treatment. Informative value of this
      test fell with detoxication contrary to plasma MMP value which correlated with
      the degree of intoxication and remained informative through detoxication being
      able to show even residual subclinical toxicity. The MMP test is a method of
      choice in assessing intoxication in patients with AOMP and its complications.

PMID- 9662973
TI  - [The explanation of safety parameters of 1.32 microm YAG-Nd laser radiation with
      1.32 km wave in middle ear manipulations and its use in tympanoplasty].
AB  - Experimental and clinical examination was made of safety of YAG-Nd laser
      radiation with wave length 1.32 microm. Such radiation is applied in middle ear
      manipulations. In surgical treatment of otitis media purulenta chronica YAG-Nd
      laser warrants more accurate, rapid and safe performance of a number of intricate
      tympanoplastic techniques. At the same time laser cannot replace routine
      microsurgical instruments which are used in the most part of the surgical
      intervention.

PMID- 9662974
TI  - [Changes in systemic and local immunity in patients with acute and chronic
      purulent sinusitis in response to regional lymphotropic immunostimulating
      therapy].
AB  - We studied the effects of regional lymphotropic immunostimulating therapy on
      alterations in immunoglobulins levels both in blood serum and paranasal sinuses
      mucosal secretion in patients with acute and chronic purulent sinusitis.
      Solutions of tactivin, lidase and novocain were administered into the area of the
      submaxillary lymph nodes. The effect was compared to that obtained after
      subcutaneous administration of tactivin and conventional therapy. No reliable
      alterations in systemic humoral immunity in response to lymphotropic
      immunostimulating therapy was reported in acute sinusitis, while in chronic
      sinusitis an increase in initially low IgA occurred. Regional lymphotropic
      administration of tactivin promoted a pronounced decrease in the initially
      elevated levels of SIgA, IgA and IgG in the secretion of paranasal mucosa in
      acute purulent sinusitis, and an increase of basaline lowered SIgA, a fall in the
      IgG concentration in chronic purulent sinusitis. This is indicative of
      effectiveness of this method of immunostimulator administration on local
      immunological reactivity of the mucous membrane.

PMID- 9662975
TI  - [Lectin-reactive immune complexes in plasma in ENT diseases].
AB  - The content of circulating immune complexes (IC) interacting with plant lectins
      from Canavalia ensiformis (Con A), phaseolus vulgaris (PHA) and wheat germ (WGA)
      was examined in blood plasma of healthy donors and patients with ENT diseases (n
      = 36). It was found that the level of PHA- and WGA-reactive IC in patients with
      laryngeal carcinoma was significantly higher than in control, whereas only the
      level of WGA-reactive IC was elevated in patients with scleroma. The level of
      ConA-reactive IC was statistically uniform in control and both ENT diseases.

PMID- 9662976
TI  - [Criteria and duration of temporary disability in ENT diseases].

PMID- 9662977
TI  - [The experience of reconstructive surgery in patients after surgeries of the
      ear].
AB  - The article deals with the experience gained by the authors in reconstructive
      surgery after radical operations on the ear. Three variants of surgical
      interventions were used. Indications to them are presented based on
      pathomorphological characteristics of the postoperative cavity and function of
      the internal ear. Anatomic and functional results of the operation variants are
      compared.

PMID- 9662978
TI  - [Regencur hydrogel sinus absorption in the treatment of chronic purulent
      sinusitis].
AB  - Local application of hydrogels based on the sorbent regencur with dioxidine was
      tried for efficacy against chronic purulent maxillary sinusitis in 30 patients
      versus matched controls. Changes in the subjective and objective manifestations
      of the disease were registered on the sensor-analog and visual-analog scales. The
      findings indicate higher efficacy of regencur hydrogels with dioxidine.

PMID- 9662979
TI  - [Low-frequency vibrations in the treatment of patients with acute maxillary
      sinusitis and ethmoiditis. Non-specific resistance and immunity].
AB  - The authors present clinicoroentgenological and immunological evaluation of low
      frequency mechanical intermittent biovibromassage used in the treatment of acute
      maxillary sinusitis alone and in its combination with ethmoiditis. The massage
      provides simple-in-use and effective impact on inflammation in the cells of the
      ethmoidal labyrinth. It can be practiced both in hospital and outpatiently.

PMID- 9662980
TI  - [Combined treatment of chronic hypertrophic pharyngitis in children].
AB  - The trial of fluctuating current in combined treatment of 94 children (age 3-14
      years) with chronic hypertrophic pharyngitis proved superior to the conventional
      treatment in the control patients: the response rate 85.7-92.5% versus 52.9%,
      respectively. Combined treatment including fluctuating current is thought
      effective in children with chronic hypertrophic pharyngitis.

PMID- 9662981
TI  - [Clinical trial of a new topical anti-histamine agent histimet in the treatment
      of seasonal allergic rhinoconjunctivitis].
AB  - 21 patients with seasonal allergic rhinoconjunctivitis (SAC) entered the trial of
      a new topical antihistamine drug histimet (levocabastine). The drug is available
      as a nasal spray and eye drops. The relief of the main symptoms of SAC occurred
      15-20 min after histimet introduction into the nose or eye. The effect of a
      single procedure lasted for 12 hours. Regression of SAC basic symptoms continued
      for 7 days after using histimet. A significant improvement of life quality was
      observed. Good effect achieved in 90% of the patients characterizes histimet as
      an effective new modality in SAC management.

PMID- 9662982
TI  - [The modification of posterior tamponade in nasal bleeding in children with
      hemoblastoses].

PMID- 9662983
TI  - [A case of infectious mononucleosis (monocytic pharyngitis)].

PMID- 9662984
TI  - [Long-term stay of foreign bodies in the left frontal sinus and left periorbital
      area].

PMID- 9662985
TI  - [A rare case of tumor-like mass in the nasopharynx].

PMID- 9662986
TI  - [Foreign body extraction from esophageal diverticulitis].

PMID- 9662987
TI  - [Acute mastoiditis in a patient with chronic lymphoid leukemia: a favorable
      outcome].

PMID- 9662988
TI  - [Oropharyngeal lesions in infectious diseases].

PMID- 9662989
TI  - [Problems of psychosomatics and somatopsychiatrics in internal medicine].
AB  - The past 2 decades in our country has been marked by the population's poorer
      health status, the obvious tendency for the incidence of many somatic and mental
      diseases to increase. The problem of somatogenic mental diseases and disorders
      diagnosed in the presence of a somatic disease merits particular attention. The
      paper considers the background of psychosomatics and somatopsychiatrics, presents
      the authors' own findings of the mental status in patients with chronic lung
      diseases. Various somatic disease-detected psychopathological syndrome
      relationships most common in the treatment of visceral diseases are systematized.
      Emphasis is laid to the fact that the differentiation of proper mental and
      somatic diseases, the elaboration of the optimal treatment policy is possible
      only if therapeutists work in close cooperation with psychiatrists. Principles in
      the complex therapy of psychopathological disorders in patients with somatic
      diseases are given.

PMID- 9662990
TI  - [Genetic aspects of silicosis: polymorphic gene distribution frequency].
AB  - Electrophoresis and isoelectrofocusing were used to study polymorphism by 7
      genetic loci: haptoglobin (Hp), proteinase inhibitor (PI), transferrin (TF),
      Vitamin D-transporting protein (GC), complement 3 (C3), phosphoglucomutase 1
      (PGM1) and glyoxalase (GLO1) in 60 patients with silicosis and in 70 apparently
      healthy workers of the Dynamo plant. Comparison of the study groups by
      significant differences in the summary of the genetic information obtained
      suggests that 5 (Hp, C3, TF, PI, PGM1) of the 7 studied systems showed the
      hereditary features of silicosis. The gene carriers Hp*2, C3*F, PGM1*2-, PI*M1,
      TF*C1, TF*C16 TF*D, GC*R due to peculiar biochemical processes appear to have
      less adaptive potentialities and a greater likelihood of the disease on exposure
      to industrial factors.

PMID- 9662991
TI  - [Neuropsychological risk factors of ischemic heart disease].
AB  - Based on Merlin's concept of integrative individuality, the following individual
      levels in types A and type B behavior were studied: psychological (character,
      locus of subjective control), psychophysiological (temperament, emotionality,
      psychomotor activity) and neurophysiological (behavioral, electrocortical, and
      vegetative activations). The distinction in the character and temperament
      parameters between both of behavior patterns was prevalent. Several accentuated
      profiles of type A persons behavior were established according to the individual
      combination of the character and temperament indices. The profile that combined
      emotionality and activity ("passionate") was confirmed as a behavioral risk
      factor in the group of the patients with ischemic heart disease. A new test for
      differential evaluation of psychophysiological profiles of type A behavior was
      developed and standardized. In the clinical part of the investigation it was the
      most effective in revealing the psychological risk factor in patients with
      ischemic heart disease.

PMID- 9662992
TI  - [Hemodynamic effect of plasma DNA].
AB  - To reveal the hemodynamic effect of plasma DNA, the authors measured the
      concentrations of plasma DNA, the length of its molecular fragments, and
      hemodynamic resistance/Toms effect. The Toms effect was detected in all blood
      samples from 10 healthy donors and 39 patients without acute stroke caused by
      atherosclerosis of the head great arteries with and without arterial
      hypertension. There was a clear inverse relationships between the plasma
      concentrations of DNA which had only long-molecular fragments in healthy persons
      and the hemodynamic resistance of its blood flow samples. The patient blood
      plasma had significant increased DNA concentrations but their molecular fragments
      were long and short. Inverse relationships between the plasma DNA concentration
      and the hemodynamic resistance of the patients' blood flow samples had a less
      correlation coefficient due to the high proportion of short DNA molecular
      fragments. The Toms effect was shown in the DNA solution prepared only from human
      funic blood where the DNA molecular fragments were long. The Toms effect was
      absent in the solutions prepared from the commercial cattle or salmon sperm DNA
      which contained shorter DNA molecular fragments. It is concluded that plasma DNA
      has a hemodynamic effect and the origin of long-molecular fragments of DNA which
      is typical for healthy young persons and short DNA molecular fragments that
      additionally appear in patients with vascular disorders is different.

PMID- 9662993
TI  - [Stereometric analysis of cell-blood barriers].

PMID- 9662994
TI  - [Molecular mechanisms of prostatic oncogenesis].
AB  - A model of effector and regulatory determinants of the rate and coordination of
      proliferation of epithelial and stromal cells in the normal prostate in benign
      hyperplasia and cancer of the prostate was developed. The direct effector factors
      protein growth factors, the regulatory factors: activators (5-alpha-reductase,
      dehydrotestosterone, prostatic specific antigen) and inhibitors (tumor
      suppressors and metastatic suppressors, insulin-like growth factor-binding
      protein type 3) were analyzed and systematized. The molecular mechanisms
      responsible for the occurrence and progression of prostatic tumors, the role of
      the above factors, genetic changes in the chromosomes and genes, impaired
      coordination in the action of oncogenes and antioncogenes were under
      investigation. Directions of experimental search for the earlier unknown links in
      the analyzed system are outlined. The prospects for designing and using new
      diagnostic and prognostic omcomarkers and new means for the prevention and
      treatment of benign hyperplasia and cancer of the prostate are defined.

PMID- 9662995
TI  - [Liposomal forms of cytostatics in oncology].
AB  - The current state and prospects of using the liposomal forms of anthracyclinic
      antibiotics, fluoroucil agents, and platinum compounds are discussed as potential
      drugs for chemotherapy of tumors. Comparative studies of standard and liposomal
      forms of the above groups of compounds were made to determine their therapeutical
      effects.

PMID- 9662996
TI  - [Colonic microenvironment in familial helicobacter infection].
AB  - To elucidate the significance of the familial microenvironment in the genesis of
      Helicobacter infection, a clinical and instrumental investigation was made of 13
      families selected by the probands who had digestive diseases associated with H.
      pylori: gastroduodenitis and duodenal ulcer disease. The occurrence of
      Helicobacter infection and gastritis in the family members was ascertained to be
      largely determined by their concurrent residence in the limited area, i.e. by the
      way of life. The contribution of the "family" factor in antral gastritis, fundal
      gastritis, and H. pylori infection was 60.0, 40.0, and about 90.0%, respectively.
      The patients with gastroenterological abnormalities associated with H. pylori
      were found to show changes in the species-specific and quantitative composition
      of the colonic microbiocenosis, which were symptomatic and revealed by
      bacteriological studies in 47.5% of cases and severe in 32.5%. When
      antihelicobacter therapy is planned, a through treatment of all family members
      and, if possible, pets should be made. Colonic microbiocenosis should be
      monitored while treating Helicobacter infection.

PMID- 9662997
TI  - [Yeast-like fungi malassezia (pityrosporum)].

PMID- 9662998
TI  - [Yeast-like fungi malassezia (pityrosporum): clinical and immunological aspects
      fo study].
AB  - The normal flora is typified by the yeast-like fungi Malassezia (Pityrosporum).
      Successful attempts at treating patients with atopic and seborreic dermatitis,
      pityriasis versicolor, and psoriasis with antifungicides confirm the involvement
      of these fungi in the etiology and development of these diseases. In patients
      with various skin diseases, an immune response to M. furfur is specific. In those
      with psoriasis, it is characterized by the higher chemoatractant activity of
      polymorphonuclear leukocytes stimulated by a M. furfur extract and by the immune
      response of IgG antibodies with immunoreactive proteins having a molecular weight
      of 100-120 kD. Patients with atopic dermatitis show a hyperimmune IgE-mediated
      response to M. furfur, with its specific Th2-lymphocytes inducing the atopic
      cytokines (IL-4, IL-10) that stimulate allergic reactions to other allergens.
      Those with pityriasis versicolor had impaired keratinocytic pigment exchange due
      to azelainic acid produced by M. furfur. The cause of transformation of the yeast
      phase of M. furfur to the mycelial one is presumably to be changes in the
      composition of fatty acids of the sebaceous glands due to increased androgen
      concentrations.

PMID- 9662999
TI  - [Epidermal growth factor receptors and their ligands in non-small-cell lung
      carcinoma].
AB  - Investigators and clinicians have recently called attention not only to the
      clinical and morphological parameters, but to the parameters characterizing the
      biological activity of nonsmall-cell carcinoma of the lung (NSCCL) from
      biochemical and molecular biological points of view. These include production of
      epidermal growth factor (EGF) receptors (EGFR) and their ligands which are
      important auto/paracrine regulation of lung tissue formation in health and tumor
      growth. Active studies of EGFR and EGF-like peptides (mainly, EGF and alpha-TGF)
      have failed to gain an insight into their role in the pathogenesis of NSCCL. Most
      authors suppose that tumor EGFR production increases as cell atypical features
      enhance and tumors show EGFR hyperexpression as compared with intact lung tissue.
      The expression of EGF and alpha-TGF is associated with poor prognosis in NSCCL.
      Attempts at designing and clinically testing the agents that block the
      transmission of EGFR ligands within the tumor cell are well-known, which open up
      new possibilities for antitumor therapy of patients with NSCCL.

PMID- 9663000
TI  - Preventing and reducing alcohol and other drug use among high-risk youths by
      increasing family resilience.
AB  - This study examines the effects of a community-based program designed to delay
      onset and reduce the frequency of alcohol and other drug (AOD) use among high
      risk youths, ages 12 to 14, through strengthening family resilience. It is part
      of a larger five-year demonstration project funded by the Center for Substance
      Abuse Prevention (CSAP). The program was implemented in multiple church
      communities in rural, suburban, and inner-city settings. Program components of
      this study included parent or guardian and youth training, early intervention
      services, and follow-up case management services. The results show that the
      program produced positive direct effects on family resilience. The evaluation
      also found positive moderating effects on delayed onset of alcohol and other drug
      use and frequency of alcohol and other drug use among youths in the form of
      conditional relationships with changes in those family resilience factors that
      were targeted by the program.

PMID- 9663001
TI  - Social support for adolescents at risk of school failure.
AB  - Social support, widely studied as a variable that positively affects the
      adaptation of adolescents, is often less present in the lives of youths at risk
      of school failure. This study explores the social support of at-risk students,
      including who provides each of eight types of support, and the effects of
      particular types of social support on school performance outcomes. Results of
      analyses of data from students enrolled in Communities in Schools programs,
      indicate that parents and adult caretakers are major sources of social support
      for both middle and high school at-risk students. Analyses of school outcomes
      data indicate that particular types of social support are associated with
      different desirable school outcomes. The article presents implications for social
      work practice and the development of intervention strategies to enhance students'
      school performance and behavior.

PMID- 9663002
TI  - Youth crime, public policy, and practice in the juvenile justice system: recent
      trends and needed reforms.
AB  - Historically, juvenile justice policy has oscillated between rehabilitative and
      punitive approaches to managing young offenders. Policy and practice in the 1970s
      and 1980s emphasized individual treatment for young offenders in nonsecure,
      community-based programs. An increase in violent youth crime during the past
      decade has renewed interest in punishing delinquent youths. Cyclic fluctuations
      in juvenile justice policy and their relationship to policy, practice, and youth
      crime are examined. Our analysis suggests that overall crime rates have remained
      relatively stable over the past three decades and are independent of prevailing
      juvenile justice policies. The findings support the need for targeted prevention
      efforts addressing the root causes of juvenile crime. Needed policy reforms,
      public education efforts, and practice approaches are outlined.

PMID- 9663003
TI  - Addiction and the brain--Part II.
AB  - In the first part we discussed the acute and chronic effects of addictive drugs
      on the brain's reward system and the internal processes of neurons. In this part
      we discuss genetic and social influences and the implications of brain studies
      for the treatment of addiction and an understanding of its nature.

PMID- 9663004
TI  - Managed care: the iceberg and Titanic.

PMID- 9663005
TI  - Freud's preaching and practice.

PMID- 9663006
TI  - Diagnosis and its discontents.

PMID- 9663007
TI  - What is the role of obstetric complications in schizophrenia?

PMID- 9663008
TI  - Tamoxifen and beyond.

PMID- 9663009
TI  - Controlling risk.

PMID- 9663010
TI  - Protein.

PMID- 9663012
TI  - New standards for nutrients.

PMID- 9663011
TI  - New ways to look at the breast.

PMID- 9663013
TI  - Sentinel node biopsy.

PMID- 9663014
TI  - Exercise: how much?

PMID- 9663015
TI  - I recently nursed my daughter, who is in medical school, through an illness that
      turned out to be hepatitis C. We were in close contact in the same house and
      shared meals. How likely am I to get hepatitis myself? Is there anything I can
      take to prevent it?

PMID- 9663016
TI  - I would like to know if it is ever too late to begin hormone replacement therapy
      to protect against heart disease and osteoporosis. My 84-year-old mother has high
      blood pressure and has never drunk much milk, so is she at risk of both these
      conditions? Wouldn't she benefit from estrogen?

PMID- 9663017
TI  - Colon cancer screening. Early detection is key.

PMID- 9663018
TI  - Health tips. Bicycle helmets.

PMID- 9663019
TI  - Until there's more information, caution advised in using tamoxifen or raloxifene
      for breast cancer prevention.

PMID- 9663021
TI  - Sun sensitivity. Some drugs and products can cause skin reactions.

PMID- 9663020
TI  - Exercise and osteoporosis. Staying active--safely.

PMID- 9663022
TI  - Fish and heart health. Make fish a regular on your plate.

PMID- 9663023
TI  - I've heard that a drug used to counter stomach acid can treat hives. Could you
      tell me more?

PMID- 9663024
TI  - Our 2-year old grandson will stay with us for a couple of weeks this summer. He
      tends to have tantrums. Any advice on how to handle these?

PMID- 9663025
TI  - The changing face of dentistry--the future of gerodontology.

PMID- 9663026
TI  - The efficacy of antimicrobial mouth rinses in oral health care.
AB  - There is growing public recognition of the importance of oral health, as
      symbolized by the theme. "Oral Health for a Healthy Life" proposed for the 1994
      World Health Day. In this report, the efficacy of antimicrobial mouth rinses,
      mainly Listerine, was reviewed by three investigators who are working as a
      microbiologist, a microbiologist, a dentist, and a dental hygienist participating
      in oral health care. Listerine, an antimicrobial mouth rinse, completely killed
      microorganisms in 10 to 30 seconds; the microbes includes methicillin-resistant
      Staphylococcus aureus, Streptococcus pyogenes, Helicobacter pylori, Candida
      albicans, Streptococcus mutans, Actinomyces viscosus, Porphyromonas gingivalis,
      Prevotella intermedia, and Actinobacillus actinomycetemcomitans. Listerine was
      also weakly effective in inactivating human immunodeficiency viruses. Bacteria in
      samples collected from human dental plaque and saliva were completely killed
      within 30 seconds when exposed to Listerine. When saliva samples were collected
      from subjects who had rinsed their mouths with 20 ml of Listerine or 1:50 diluted
      povidone-iodine, levels of viable anaerobic bacteria in the samples were reduced
      to 1%. When Listerine was used for oral surgery such as tooth extraction and
      periodontal surgery, the agent was effective in relieving toothache. This was
      probably due to a decrease in oral bacteria by the antimicrobial action of
      Listerine, leading to lowering the inflammatory response of the host. The use of
      antimicrobial mouth rinse during dental treatments such as endodontic treatment
      proved effective for more reliable infection control. In Japan, there are an
      increasing number of elderly and medically compromised hosts who are potentially
      at risk for developing pneumonia due to silent aspiration of microbes in the oral
      cavity and throat. For the aged with such potential risk, using of antimicrobial
      mouth rinse may be effective in preventing dental plaque accumulation when used
      in addition to the mechanical control of plaque, since they tend to have
      difficulty in brushing teeth by themselves. Indeed, the use of antimicrobial
      mouth rinse in these elderly people proved useful not only in preventing
      bacterial pneumonia, but also in improving their quality of life by preserving
      their oral health.

PMID- 9663027
TI  - The effectiveness of the "Clean-Area-System" for infection control in the dental
      clinic.
AB  - The use of effective infection control procedures and universal precautions in
      dental clinics, prevents cross contamination that could extend to dental health
      care workers and patients. The present study was initiated to investigate
      airborne environmental contamination in the dental clinic by viable cell count of
      oral streptococci grown on Mitis-Salivarius and blood agar plates. The reduction
      of the contamination by the "Clean-Area-System" was evaluated. "Andersen-Microbe
      Sampler-Apparatus" and "Laser-Particle-Counter-System" were used for sampling and
      counting the bacterial cells and airborne dust, respectively. Numbers of viable
      cells counted as total colony forming units (CFUs) in the dental clinic were
      found to be significantly higher than those in the waiting room and the research
      laboratory. We found that the "Clean-Area-System" significantly reduced the CFUs
      grown on blood agar plates (p < 0.05), and that using the "Clean-Area-System"
      combined with the "Extra-Oral-Vacuum-Aspirator" is desirable in dental procedures
      such as cavity preparation. The "Extra-Oral-Vacuum-Aspirator" reduced airborne
      environmental contamination during tooth cutting and ultrasonic scaling
      procedures. In non-grinding procedures, this system proved to be very useful for
      infection control in the operative area. The authors concluded that the combined
      use of "Clean-Area-System" (dust collection ablation) and "Extra-Oral-Vacuum
      Aspirator" (absorb dust ablation) was effective to reduce airborne environmental
      contamination in the dental clinic. We also fully confirmed that oral
      streptococci were an adequate indicator in the assessment for infection control
      in dental institutions.

PMID- 9663028
TI  - Caries development in children from 1.5 to 3 years of age: a longitudinal study.
AB  - This study was designed as a prospective clinical caries prevalence study
      starting with children at 1.5 years of age. The subjects were 374 children who
      were born between 1989 and 1991. All subjects visited a public health center in
      Kunitachi-city, Tokyo, at 1.5 years, 2 years, and 3 years of age. All the
      children and parents have followed preventive dental care guidance. Dental caries
      were always examined by one of the authors. The caries prevalences at 1.5 years,
      2 years, and 3 years of age were 6.1%, 14.7%, and 31.8%, respectively. The mean
      dft at 3 years of age in children who developed caries before 2 years of age was
      significantly greater than that in children caries free at 2 years of age. The
      findings from the current study showed that children who develop caries before 2
      years of age are at greater risk for dental caries.

PMID- 9663029
TI  - Dentin bridge formation following direct pulp capping in dog's.
AB  - The effectiveness of two different calcium hydroxide pastes; "Calvital and
      "Dycal", for the direct pulp capping in dog's permanent teeth with incompletely
      formed roots were evaluated in this study. Forty-eight vital permanent premolar
      teeth with incompletely formed apices were obtained from 6 dog's (6 months of
      age). Exposure sites on contralateral pairs of teeth were capped with either
      "Calvital" or "Dycal". Then intravenous injections of tetracycline were
      administered to the dogs at various intervals. Animals were sacrificed at 56
      days. The teeth were fixed, undecalcified ground sectioned, observed by
      microradiography, and evaluated by ultraviolet light. In cases treated with
      "Calvital", a fluorescent line resulting from tetracycline administration 7 days
      after experimental procedures was seen in the newly formed dentin bridge. In
      cases treated with "Dycal", a fluorescent line resulting from tetracycline
      administration 14 days after experimental procedures was seen in the newly formed
      dentin bridge. Continued physiological root formation was observed well in all
      teeth. This experiment may explain why some "Dycal" failures occur in the earlier
      postoperative periods; serves as a stimulus potential for a hardening reaction.

PMID- 9663030
TI  - A longitudinal study of the development of crowded dental arch.
AB  - It is important to determine both where and when in the process of dental arch
      development crowding occurs. The authors investigated 81 children (boys/37,
      girls/44). These children were developing permanent dentition without early loss
      of deciduous or permanent teeth, which is considered to be one of the causes of
      malocclusion. Impressions were taken from subjects who had normal, spaced, or
      crowded permanent dental arch, and longitudinal casts made every two months from
      three years of age. In both the maxilla and the mandible, the transition to the
      crowded condition most often occurred (maxillary: 84.6%, mandibular: 64.5%) at
      the time of eruption. Crowding condition was also caused by the eruption of other
      teeth; however, this was rare. The maxillary and mandibular crowding mostly
      occurred (maxillary: 69.2%, mandibular: 77.4%) in the anterior teeth. It was
      seldom observed in the premolar and first molar regions.

PMID- 9663031
TI  - Mechanical properties of buccal compact bone of the mandibular ramus in human
      adults and children: relationship of the elastic modulus to the direction of the
      osteon and the porosity ratio.
AB  - With recent advances in computers, the finite element method has been used for
      stress analysis of bone. In particular, the dynamic behavior of the jaw bone has
      been a subject of interest and analyzed by this method. However as the elastic
      modulus needed for this method, a uniform value is used without considering
      differences according to site or direction. Therefore, we measured the elastic
      modulus at various sites and in various directions of the mandible in adults and
      children. In addition, the association between the elastic modulus and
      histological structures was evaluated. Ten specimens of dried mandible from human
      adults and children were used. The elastic modulus was measured in two regions
      prepared by equally dividing the ramus of the mandible into lower and upper
      regions. Samples of 6 mm x 960 microns x 425 microns were collected from the
      buccal compact bone. The elastic modulus was measured using a three-point bending
      test. After measurement, the direction of the osteon was examined using SEM. The
      porosity ratio was also measured after CMR were taken. In both adults and
      children, anisotropy in the elastic modulus of each direction in the upper region
      was similar to the anisotropy in unidirectional fiber reinforced composite
      materials, but not in the lower region. The elastic modulus decreased slightly
      with an increase in the angle of the direction of osteons to the longitudinal
      axis of specimens. The direction of osteon may significantly influence anisotropy
      in the elastic modulus. The elastic modulus in adults was higher than in children
      in all directions. The porosity ratio in adults was smaller than that in children
      in all directions. The difference in the porosity ratio between adults and
      children may significantly influence the value of the elastic modulus.

PMID- 9663032
TI  - A study of the internal structure of the mandibular ramus in Japanese.
AB  - To clarify the internal structure of the mandibular ramus in Japanese adults, we
      performed bone morphometry. Specimens were obtained from four areas: the mid-area
      between the mandibular foramen and the lowest point of the mandibular notch,
      areas immediately above and below the mandibular foramen, and the mid-area
      between the mandibular foramen and the mandibular angle. The mandibular ramus was
      divided into the anterior and posterior parts, and morphometric analysis was
      performed on the four areas in each part. The percentage of the trabecular bone
      area in spongy bone was higher in the anterior part than in the posterior part.
      In both the anterior and posterior parts, the percentage of trabecular bone was
      the highest in the most inferior area. Trabecular bone was thicker in the
      anterior part than in the posterior part. Both in the anterior and posterior
      parts, trabecular bone was the thickest in the most inferior area. The
      arrangement of trabecular bone was more complicated in the anterior part than in
      the posterior part. Trabecular bone was most frequently arranged in the
      anteroposterior direction. In the superior area of the posterior part, much
      trabecular bone ran from the posterior buccal side toward the anterior lingual
      side. Compact bone was thicker in the anterior part than in the posterior part
      and on the buccal side than on the lingual side. No age-related changes were
      observed in any element of trabecular bone structure.

PMID- 9663033
TI  - Adhesion of periodontal bacteria to titanium, and titanium alloy powders.
AB  - In this study, the adhesion of radioactively labeled Actinomyces viscosus (A.
      viscosus), Actinobacillus actinomicetemcomitans (Aa) and Porphyromonas gingivalis
      (P. gingivalis) to titanium (Ti) and Ti-6-Al-4V alloy (Ti-alloy) coated with
      albumin or human saliva was investigated. All the tested bacteria displayed
      greater attachment to Ti-alloy than to Ti. P. gingivalis exhibited less adhesion
      to Ti and Ti-alloy than did the other bacterial strains. Adhesion of A. viscosus
      and Aa was greatly reduced when Ti or Ti-alloy were coated with albumin or
      saliva. P. gingivalis demonstrated a lesser reduction in adhesion to albumin or
      saliva-coated surfaces. The results show that oral bacteria have different
      adhesion affinities for Ti and Ti-alloy and that both albumin and human saliva
      reduce bacterial adhesion.

PMID- 9663034
TI  - Soft tissue response to plaque formation at different implant systems. A
      comparative study in the dog.
AB  - The aim of the present experiment was to study the location and composition of
      plaque associated lesions in the mucosa adjacent to implant systems that differed
      with respect to both geometry and dimension. At day 0 extraction of the
      mandibular premolars were performed. After a healing period of 3 months, fixtures
      of the Astra Tech Implants, Dental System, the Branemark System and the ITI
      Dental Implant System were installed. In each mandibular quadrant 1 fixture of
      each implant system was installed in a randomized order. A period of plaque
      control was initiated. Following another 3 months of healing, abutment connection
      was performed in the 2-stage systems (the Astra Tech Implants, Dental System and
      the Branemark System). After 1 month, the plaque control measures were abandoned
      and plaque formation was allowed for 5 months. The animals were killed and
      biopsies representing each implant region obtained. The tissue samples were
      prepared for light microscopy and exposed to histometric and morphometric
      measurements. The present study demonstrated that plaque formation resulted in
      the establishment of an ICT lateral to a pocket epithelium. The lesion was found
      to be similar regarding extension and composition in the peri-implant mucosa of
      the 3 implant systems tested. The vertical extension of the ICT was in all
      systems within 91-99% of the vertical dimension of the junctional epithelium. The
      marginal bone level, measured from the abutment/fixture (PS) border, did not
      differ between the three systems.

PMID- 9663035
TI  - A meta-analysis of implants in partial edentulism.
AB  - A meta-analytic technique was used to estimate the survival of implants
      supporting bridges or single crowns in partially edentulous patients. A survey of
      the literature revealed 66 studies, published between 1986 and 1996. Nine studies
      on single implants and 10 studies on fixed partial dentures met the inclusion
      criteria for the meta-analysis. Data from a total of 2686 implants, 570 single
      crowns (SC) and 2116 in fixed partial dentures (FPD), were analyzed. In order to
      calculate annual survival rates for individual studies a life-table analysis was
      conducted. Maximum follow-up time ranged between 1 and 8 years. After 1 year the
      success rate was calculated to be at least 85.7% for FPD and 97.2% for SC. When
      the results from the FPD studies were pooled the survival rate was 93.6% after 6
      7 years. The corresponding value for SC was 97.5%.

PMID- 9663036
TI  - Marginal bone levels at single tooth implants with a conical fixture design. The
      influence of surface macro- and microstructure.
AB  - The concept of a conical implant design to accommodate single tooth replacement,
      has previously been shown to result in excessive bone loss, around the machined
      titanium conical collar, usually down to the 1st thread. This unusually
      aggressive loss of bone was shown to occur within a short period of time, post
      loading, with greater than 3 mm of bone loss occurring within the 1st 6 months to
      1 year. The influence of implant design, surface texture and microleakage have
      all been highlighted as a potential cause. A modification of the surface
      structure, both at the macroscopic and microscopic level, as well as an altered
      fixture-abutment interface design has resulted in the maintenance of marginal
      bone around a single tooth titanium implant with a similar conical design. The
      radiographic follow-up of 33 implants loaded for up to 4 years, has revealed, by
      comparison, a most favourable maintenance of marginal bone around the conical
      collar, with a mean marginal bone loss of 0.32 mm mesially and 0.34 mm distally
      for the whole group. The cumulative mean marginal bone loss mesially and distally
      is 0.42 mm and 0.40 mm from 1 to 2 years, 0.54 mm and 0.43 mm from 2 to 3 years,
      0.51 mm and 0.24 mm from 3 to 4 years, and 0.62 mm and 0.60 mm for implants past
      their 4 year recall.

PMID- 9663037
TI  - Histological morphology of the e-PTFE/tissue interface in humans subjected to
      guided bone regeneration in conjunction with oral implant treatment.
AB  - The purpose of the present investigation was to study the histological morphology
      of the e-PTFE membrane/tissue interface in 5 humans subjected to GBR treatment in
      conjunction with oral implant treatment. Oral implants (Branemark System) were
      inserted in extraction sockets 1 to 2 months after extraction of periodontally
      diseased teeth. The implants were placed approximately 2 mm below the surrounding
      bone margins. Specially designed 3 mm high cover-screws with horizontal slits for
      tissue ingrowth were applied to the implants and covered with e-PTFE membranes
      (GoreTex Augmentation Material). Re-entry was made 7 months later, except in 1
      case where the membrane was removed 1 month postoperatively due to exposure and
      infection. In the remaining 4 sites, circular biopsies comprising membranes,
      tissues and cover-screws were retrieved. The specimens were fixated, processed
      and sectioned for light- and transmission electron microscopy. The space between
      the membrane and the cover-screw was occupied by fibrous tissue and varying
      amounts of bone. A cell- and vessel-rich fibrous tissue separated the bone from
      the membrane in the majority of the specimens. The membrane itself was penetrated
      by fibrous tissue. Fibroblasts and macrophages were the main cell types found in
      the fibrous tissue. The presence of irregularly shaped cells and unevenly
      distributed collagen fibres, indicated that the absence of bone formation may be
      due either to micromovements in the e-PTFE/tissue interface or to formation of
      fibrous tissue underneath the membrane by penetrating fibroblasts or a
      combination of these 2 phenomena.

PMID- 9663038
TI  - Bovine hydroxyapatite for maxillary sinus grafting: comparative histomorphometric
      findings in sheep.
AB  - This experimental study in animals examines the value of bovine hydroxyapatite as
      grafting material in one-stage sinus lift procedure. The Schneiderian membrane
      was elevated from extraorally in 54 sinuses of 27 adult female mountain sheep.
      Two titanium plasma-flame-spray coated cylindrical implants were placed in each
      sinus in the same session. In 2 groups of 18 sinuses each, the subantral hollow
      space was filled with bovine hydroxyapatite and autogenous cancellous bone from
      the iliac crest, respectively. Eighteen sinuses that were left empty served as a
      control group. Polyfluorochrome sequential labelling (tetracycline, calcein
      green, alizarin complexon) was carried out 4 weeks postoperatively, 2 weeks
      before the animals were sacrificed, and halfway through the observation period to
      assess new bone formation. The selected observation periods were 12 weeks, 16
      weeks, and 26 weeks. Six sinuses per observation period and test group were
      available for histologic evaluation. All implants showed favourable
      osseointegration into local bone. New bone formation was observed in a triangular
      area bound by the implant surface, the local buccal antral wall, and submucous
      connective tissue in all implants. Bovine hydroxyapatite adjacent to local bone
      was mainly surrounded by bone tissue. There was a great variation in the extent
      of bony sheathing of the hydroxyapatite particles, irrespective of the animals'
      survival time. Macrophages were found around HA particles that were not
      surrounded by bone as well as on free implant surfaces. The mean length of the
      bone-implant bond was 3.86 mm in the group of empty sinuses, 4.87 mm in the group
      augmented with hydroxyapatite, and 5.66 mm in the group augmented with autogenous
      cancellous bone. During the observation period, the relative length of bone in
      direct contact with the implant surface increased from 20.0% to 25.1% in the
      control group, from 30.4% to 35.5% in the group treated with autogenous
      cancellous bone, and from 27.4% to 34.7% in the HA group. Autogenous cancellous
      bone showed a significantly greater bone-implant contact than did the control
      group (P = 0.0004) and the HA group (P = 0.0499). When the apical implant
      portions were examined separately, both HA (P = 0.006) and autogenous cancellous
      bone (P = 0.005) showed a significantly better bone-implant bond than did the
      control group.

PMID- 9663039
TI  - Bovine hydroxyapatite for maxillary sinus augmentation: analysis of interfacial
      bond strength of dental implants using pull-out tests.
AB  - This study examines the effect of sinus lift surgery using bovine hydroxyapatite
      on the bone anchorage of titanium plasma flame-spray-coated cylindrical implants.
      A total of 54 implants were placed in the lateral bony antral walls of 27
      mountain sheep. Host site augmentation was done simultaneously using bovine
      hydroxyapatite and autogenous cancellous bone from the iliac crest in 18 sinuses
      each. The bone walls of the remaining 18 sinuses received no augmentation. Pull
      out tests were carried out at 12, 16, and 26 weeks, revealing a significant
      influence of the implants' residence time on pull-out strength (P = 0.004). The
      implants of the non-augmented group and those of the group augmented using
      cancellous bone showed a linear increase in pull-out strength to 169.8 N and
      523.7 N, respectively, until the 26th week. The implants of the group augmented
      with bovine hydroxyapatite exhibited the highest initial pull-out strength (325.1
      N) that further increased to 521.8 N until the 26th week. All in all, this group
      showed a significantly greater pull-out strength tan did the negative control
      group (P = 0.03).

PMID- 9663040
TI  - Localized ridge augmentation using a micro titanium mesh: a report on 27 implants
      followed from 1 to 3 years after functional loading.
AB  - The present paper describes the clinical and radiographic healing results of 27
      implants followed from 1 to 3 years after functional implant loading. Prior to
      implant placement, alveolar ridges with insufficient bone volume were augmented
      using autogenous bone grafts and a micro titanium mesh for graft stabilization.
      After a mean interval of 5.2 months implants were installed. Following an
      osseointegration period of on average 7.2 months, implants were supplied with
      suprastructures. The mean loading period for the 27 implants was 21 months. All
      implants exhibited ankylotic stability and healthy peri-implant soft tissues. The
      detailed analysis of clinical parameters (probing depth, level of mucosal margin,
      attachment level, modified plaque and sulcus bleeding indices) and radiographic
      measurements (crestal bone level), revealed findings similar to those at implants
      placed into non-augmented bone. Peri-implant bone resorption was calculated to be
      1.0 mm for the 1st year after implant loading and 0.1 mm for the following year.
      Pain, suppuration or semilunar bone defects were absent at all implants. It was
      concluded that loaded dental implants which have been inserted into an augmented
      alveolar ridge using autogenous bone grafts and a micro titanium mesh for graft
      stabilization, demonstrate clinical and radiographic findings similar to those of
      implants placed into a pristine ridge.

PMID- 9663041
TI  - Comparison of Branemark fixture integration and short-term survival using one
      stage or two-stage surgery in completely and partially edentulous mandibles.
AB  - The aim of this prospective study was to compare the clinical integration and
      survival of Branemark fixtures when using the conventional 2-stage surgical
      procedure to 1-stage surgical approach in completely and partially edentulous
      mandibles. A total of 85 patients were consecutively treated for partial (n = 35)
      or complete (n = 50) mandibular edentulousness. Fixtures removed because of
      mobility, pain or infection were counted as failures. The first 10 patients of
      each group were selected for radiographical analysis of crestal bone changes 1
      year after prosthesis insertion. In 33 patients with edentulous mandibles, 170
      fixtures were placed in a 1-stage approach. In this group, 4 fixtures (2.4%) were
      lost prior to prosthetic restoration. Seventeen edentulous patients received a
      total of 70 fixtures in a 2-stage procedure. Out of these, 5 fixtures (7.1%) were
      lost at abutment connection. In 17 partially edentulous patients, 41 fixtures
      were inserted in a 1-stage approach. Two fixtures (5%) were lost in this group.
      Finally, 18 partially edentulous patients received a total of 49 fixtures in a 2
      stage procedure. Out of these, 6 fixtures (12%) were lost at abutment connection.
      In total 313 of the 330 installed mandibular implants were loaded between 6 and
      12 months (94.8% success). No further losses occurred in the implants functioning
      at least 1 year (267 implants) or at least 2 years (59 implants). Statistical
      analysis (Chi square test) revealed no difference in fixture survival between the
      treatment modalities. Radiographical analysis after 1 year of functional loading
      showed the typical bone resorption changes up to the most coronal implant thread
      in both modalities. Although this study pertains to relatively early loading of 2
      years, the results seem to indicate that in the mandible a 1-stage surgical
      approach with Branemark fixtures may be as predictable as the conventional 2
      stage procedure.

PMID- 9663042
TI  - Marketing the cosmetic dental practice.
AB  - Marketing a cosmetic dental practice is a necessary element of patient education
      today. A professional relations coordinator is essential for developing
      integrated strategies that help patients understand the options available to them
      in cosmetic dentistry. Cosmetic dentistry is an evolving field that can be
      difficult for patients to fully understand. Only through patient education and
      marketing will dentists be able to expand their practices to include cosmetic
      dentistry.

PMID- 9663043
TI  - The full veneer as an alternative to the full crown.
AB  - The use of ceramic veneers on the facial and incisal surfaces of teeth has become
      an integral part of our esthetic armamentarium. The success rate on these
      restorations has led to increased optimism and expanded applications. The full
      veneer uses bonded ceramic veneers to restore additional tooth surfaces. The
      result is a highly esthetically pleasing restoration that is functional and very
      conservative compared with traditional crowns.

PMID- 9663044
TI  - Optimal esthetics with implant dentistry.
AB  - When implants were first introduced to dentistry, osseointegration was considered
      the most important factor, with cosmetic considerations not an issue at the time.
      The possibility of being able to make a foreign body part of the human body was
      the ultimate goal. With the growing demands for larger than life restorations,
      dental implantology has entered a new age in which osseointegration is no longer
      a question but an established fact [1..]. The question has become instead which
      implant systems and abutments to choose in order to make a superstructure that
      looks like a natural tooth. This review is intended to bring information to the
      clinician about the possibilities that exist today to make lifelike teeth on
      implants.

PMID- 9663045
TI  - Long-term esthetic provisional restorations in dentistry.
AB  - The role of interim dental restorations used for indirect restorative and
      prosthodontic procedures has changed dramatically in the past several years.
      These restorations are no longer regarded as temporary restorations but rather as
      provisional restorations with distinct functions and purposes. Provisional
      restorations have become a vital diagnostic and assessment tool to evaluate
      function color, shape, contour, occlusion, periodontal response, implant healing,
      and overall esthetics. An accurate fit and margination is essential to insure and
      maintain pulpal health of the tooth. With increased demands being placed on
      provisional restorations, new materials and techniques are being developed and
      some existing protocols are being refined to accomplish the desired goals.
      Provisional restorations are often in the oral environment for several months,
      requiring a well-fabricated and stable restoration. This review is designed to
      report on current materials, techniques, and concepts in fabricating and
      maintaining long-term esthetic provisionals.

PMID- 9663046
TI  - Soft tissue contouring as periodontal plastic surgery.
AB  - Many options are available today for treatment of the cosmetic dentistry patient.
      Composites, veneers, and porcelain crowns have become an art form, with the
      gingival tissue serving as the frame. Clinicians providing cosmetic dental
      services must keep aware of the different techniques available for soft tissue
      contouring. Only recently has periodontal plastic surgery been presented at
      dental meetings, and little information exists in the research literature. This
      review brings the practicing dentist up to date on scientific and clinically
      relevant articles on soft tissue contouring. By working with the shape and
      contour of the gingiva, a more complementary esthetic final result is possible.

PMID- 9663047
TI  - Gateways to patient acceptance of cosmetic procedures.
AB  - Many clinicians have the desire to incorporate cosmetic dentistry into their
      everyday office procedures. It is often challenging to gain patient acceptance
      for these procedures. This review explores a way in which two services, tooth
      whitening and chairside esthetic mockups, can be used to introduce patients to
      cosmetic dentistry, to educate patients, and to increase happiness in the office
      while providing worthwhile services.

PMID- 9663048
TI  - The esthetics of anterior tooth aging.
AB  - As generations proceed to reinvent themselves in an effort to achieve and
      maintain youth, cosmetic dentistry faces one of its greatest and most persistent
      challenges: the restoration of an aging smile. Although the need for this
      restorative therapy has not yet been adequately studied, the momentum continues
      to build as aging teeth exhibit physical characteristics that affect their
      function as well as appearance. This review presents the most common factors
      influencing the esthetics of anterior tooth aging: coloration; wear and the
      effects of erosion, attrition, abrasion, and abfraction; and position of teeth
      relative to each other and surrounding tissues. While dental science seeks to
      understand how well age-specific restorative procedures can affect patients, the
      question of the necessity of this therapy remains. Should a healthy smile require
      treatment? Only time will reveal at what cost and to what extent a younger
      appearance plays a role in dental science.

PMID- 9663049
TI  - Indirect posterior restorations: steps to clinical success.
AB  - Continued advances in adhesive dentistry allow predictable bonding of tooth
      supporting restorations using conservative preparation. As tooth-colored
      restorative materials continually yield improved durability and esthetic
      properties, treatment options expand. There has been slow acceptance of both
      direct and indirect posterior esthetics. The focus of this article is to review
      clinically proven techniques that when followed will consistently result in long
      term functional indirect restorations.

PMID- 9663050
TI  - Vital tooth bleaching with Nightguard vital bleaching.
AB  - Between July 1994 and May 1996, several landmark articles were published
      concerning the safety and efficacy of vital tooth bleaching with 10% carbamide
      peroxide in a customfitted tray. The American Dental Association (ADA) published
      guidelines for ADA acceptance, and three products received approval. Long-term
      clinical trials on 38 patients indicated 92% successful bleaching after 6 weeks
      of treatment. Results were stable in 74% of the patients at 1.5 years, and in 62%
      of the patients at 3-year follow-up with no further treatment. Clinical pulpal
      studies and periodontal studies indicated no detrimental safety problems,
      although some laboratory cell studies suggested concerns. The noncarcinogenic
      potential of 10% carbamide peroxide was established in animal studies. Successful
      bleaching of tetracycline-stained teeth was achieved after 6 months of treatment,
      with no tooth problems detected clinically or by scanning electron micrograph.
      Extended treatment times are effective on other stains from dentinogenesis
      imperfecta or nicotine. On insertion in the mouth, 10% carbamide peroxide
      elevated the pH in the tray and saliva. After 4 hours of clinical wear, over 60%
      of the newer, thicker materials (Opalescence [Ultraclent Products, South Jordon,
      UT] and Platinum [Colgate Oral Pharmaceuticals, Canton, MA]) was present and
      active in the tray. Nightguard vital bleaching seems to be the most cost
      efficient, user-friendly, patient-accepted method of bleaching teeth available to
      the profession and is safe and effective. Over-the-counter products can have
      harmful effects on tooth structure and may not lighten teeth.

PMID- 9663051
TI  - Using technology to market cosmetic dentistry.
AB  - The presentation of proposed dental treatment has been hampered by the absence of
      visual communication technologies. New high tech dentistry-related tools permit
      efficient production of case presentations for cosmetic dentistry and restorative
      dentistry. This review describes how to create computer-based case presentations
      using Microsoft PowerPoint (Microsoft Corp., Redmond, WA) and visual treatment
      proposals using Microsoft Word for Windows.

PMID- 9663052
TI  - Full-mouth porcelain rehabilitation.
AB  - The understanding and development of cosmetic choreography as both an art and a
      science has enabled clinicians to restore structure and function to damaged
      dentitions while restoring aesthetic harmony to their patients' oral and facial
      appearance. This review presents a case of full-mouth, all-porcelain
      rehabilitation, embracing the interplay between diagnosis, treatment planning,
      material selection, and cosmetic choreography.

PMID- 9663053
TI  - Use of the Empress all-ceramic restoration system.
AB  - New dental materials and techniques have been introduced in the past few years to
      fabricate aesthetic ceramic restorations with improved strength,
      biocompatibility, resistance to wear, and better fit. Aesthetic concerns and
      increasing demand for tooth-colored posterior restorations have led to a number
      of all-ceramic restorations such as IPS Empress (Ivoclar-Williams, Amherst, NY).
      The Empress system offers superior aesthetics and physical properties. New
      generation ceramics along with the current adhesive techniques have resulted in
      the ability to provide higher strength, therefore indicating crowns for posterior
      restorations as well. These materials are being used more frequently and in more
      extensive oral prosthetic rehabilitations such as the case that will be
      presented. We discuss the different properties and advantages of IPS Empress.

PMID- 9663054
TI  - Creating facial harmony with cosmetic dentistry.
AB  - With the increased awareness that optimal cosmetic dentistry can have on self
      image, self-esteem, and self-confidence, patients are no longer just wanting to
      close gaps or whiten their smiles. Patients are becoming very conscious of the
      size, proportion, and position of their teeth as related to their smile and face.
      By incorporating the art and science of cosmetic dentistry into our enhancement
      therapy, we are able to create excellent results on a consistent basis. This
      review explores the impact that cosmetic dentistry can have on creating facial
      harmony. The discussion demonstrates the importance of a proper esthetic
      diagnosis as well as a thorough bioesthetic evaluation of each patient. This
      review also stresses the importance of an objective and subjective assessment and
      how a detailed evaluation of each patient can help create harmonious and natural
      smiles.

PMID- 9663055
TI  - Nonsurgical facelifts via cosmetic dentistry: fact or fiction.
AB  - The role that cosmetic dentistry can play in improving one's overall facial
      esthetics has become increasingly more meaningful to patients, dentists, and
      physicians as elective cosmetic procedures continue to gain momentum and
      acceptance in today's Western culture. By incorporating fundamental principals of
      proper smile design into a total esthetic facial enhancement treatment plan,
      dramatic improvements may be realized. As cosmetic dentists, maxillofacial
      surgeons, and orthodontists continue to make successful strides with their
      physician counterparts, they must continue to emphasize the key role that the
      smile commands. Although a review of current literature discloses few references
      to the specific topic of facial enhancements through cosmetic dentistry, it is
      nonetheless a topic for further discussion.

PMID- 9663056
TI  - Composite smile designs: the key to dental artistry.
AB  - Patients seeking to improve the appearance of their smiles have driven the
      profession toward more challenges in esthetic dentistry to answer their needs.
      Better smiles are being equated with better living. Direct composite veneering
      has gained tremendous popularity over the past few years because the procedure
      can be done in one single appointment for a reasonable fee with acceptable
      results. Materials recently put on the market require stratification build-up
      techniques to allow for the best natural results. In addition, the procedure
      gives patients the freedom of live communication and dentists the emotive
      artistic recreation of a smile composition in which anterior teeth can be
      designed and redesigned through freehand craftmanship, until both patient and
      dentist are pleased with the results. This review highlights the benefits of
      direct composite veneering, a very unique process to investigate more about tooth
      and smile designs, and suggests more effective communication between patient and
      dentist in order to achieve predictable results.

PMID- 9663057
TI  - Effectiveness of simplified dentin bonding systems.
AB  - The effectiveness of newly developed commercial dentin bonding systems (SB, MB II
      and KB) was evaluated by measuring the contraction gap width of a resin composite
      restored into a cylindrical dentin cavity prepared in an extracted human molar
      and by measuring the tensile bond strength to the flat dentin surface. In
      addition, calcium loss during dentin conditioning was analyzed using electron
      microanalyses. An experimental dentin bonding system composed of EDTA
      conditioning, GM solution priming and a bonding agent containing 10-MDP was
      employed as a control in which it was presumed that contraction gap formation was
      prevented completely. However, gap formation was observed using the three
      commercial simplified dentin bonding systems. SEM observation showed that the gap
      was formed between the resin composite and the top surface of the dentin cavity
      wall indicating that the fracture occurred at the adhesive interface, but never
      inside the dentin nor inside the resin composite.

PMID- 9663058
TI  - Acoustic emission signals from gypsum-bonded dental casting molds during thermal
      processing.
AB  - To develop a suitable heating program for the investments which affect the
      casting accuracy/defects of prostheses, a probable microstructural change of the
      gypsum-bonded investments related to the transition of refractory particles
      during thermal processing was inspected by the measurement of acoustic emission
      (AE) signals. Gypsum-bonded cristobalite and quartz investment molds were used.
      AE measurements were carried out for the specimens in an electric furnace that
      was heated/cooled at a constant rate. For the heating process of the cristobalite
      investment, high AE activities were detected in the temperature range where the
      cristobalite was transformed. However, the AE signals detected were low for the
      second run of the heating and cooling processes. Even in the heating process,
      significant AE signals were not detected for the quartz investment. For
      cristobalite investment molds, micro-cracks are initiated and developed in
      relation to the transition of cristobalite particles in the mold. This leads to
      deterioration of the mechanical properties of the cristobalite investment at high
      temperatures (melt-pouring), and may affect the fitness of cast prostheses.

PMID- 9663059
TI  - Effect of 10% phosphoric acid conditioning on the efficacy of a dentin bonding
      system.
AB  - The efficacy of a commercial total-etch wet-bonding dentin bonding system and the
      effect of conditioning using 10% phosphoric acid both on the Ca-content in the
      substrate dentin and on the efficacy of the experimental contraction gap-free
      dentin bonding system were evaluated by measuring the wall-to-wall polymerization
      contraction gap width of a commercial light-activated resin composite filled into
      a cylindrical cavity prepared in extracted human dentin. The Ca-content in the
      dentin was measured with an EDS. Complete marginal adaptation was obtained only
      in the experimental contraction gap-free dentin bonding system group. The Ca
      content in the dentin was rapidly reduced by the 10% phosphoric acid
      conditioning. It was concluded that the dentist should not decalcify the dentin
      cavity wall possibly by using a dentin conditioner such as 10% phosphoric acid
      because the resin composite paste is apt to separate easily from the decalcified
      dentin cavity wall during polymerization.

PMID- 9663060
TI  - Effect of Cr and Cu addition on corrosion behavior of Ni-Ti alloys.
AB  - The corrosion behavior of three Ni-Ti alloys with compositions as commercial
      super-elastic orthodontic wires was investigated using polished plate specimens.
      Corrosion resistance was estimated by potentiodynamic polarization measurement in
      0.9% NaCl and 1% lactic acid solutions and analysis of released metals by atomic
      absorption spectrophotometry. The influence of Cr and Cu addition on the
      structure of the surface oxide film was examined by X-ray photoelectron
      spectroscopy (XPS). Addition of 0.19 at% Cr had little effect on the structure of
      the oxide films and the corrosion resistance of the Ni-Ti alloys. For Ni-Ti-5Cu
      0.3Cr alloy, the metallic Cu was enriched at the alloy/oxide film interface,
      resulting in increased susceptibility to pitting corrosion above +1000 mV.
      However, the passive current density and the amount of released Ni were not
      significantly increased by the addition of Cu. The study showed that small
      amounts of Cr and Cu added to change the super-elastic characteristics do not
      change the corrosion resistance of the Ni-Ti alloy freely immersed in simulated
      physiological environments.

PMID- 9663061
TI  - Estimation of residual stress in dental porcelain by laser-Raman spectroscopy.
AB  - Residual stress in the surface of dental porcelain was estimated using laser
      Raman spectroscopy. Sixteen different magnitudes of residual stress were
      generated in commercial porcelain disks by tempering, ion exchange, and slow
      cooling. The specimens were analyzed using a laser-Raman spectrometer with an Ar+
      laser. The Raman shift of the largest peak near 500 cm-1 originating from silica
      was used as an indicator of the level of residual stress. For comparison, the
      residual stress in the specimen was estimated by the indentation micro-fracture
      method. The Raman shift of the porcelain increased with increasing residual
      stress at 3.7 x 10(-2) cm-1/MPa (R2 = 0.89). The increase in the Raman shift
      corresponded to the increase in compressive stress. In addition, the value of
      full width at half maximum on the peak corresponded to the residual stress (-1.57
      x 10(-1) cm-1/MPa: R2 = 0.82). These results revealed that the increase of
      residual stress in porcelain clearly appears on the Raman spectrum as an increase
      in the Raman shift. It is thus feasible to estimate residual stress in porcelain
      by laser-Raman spectroscopy.

PMID- 9663062
TI  - Effect of operator variability on dentin adhesion: students vs. dentists.
AB  - The purpose of this study was to evaluate the operator variability of two dentin
      bonding systems. Fourteen undergraduate students and ten dentists of different
      levels of clinical experience were selected. Tensile bond strengths between resin
      composite and bovine dentin using dentin adhesive systems (Clearfil Liner Bond
      II: LB II; Scotchbond Multi-Purpose: MP) bonding systems showed a large scatter
      among students and dentists. The dentists group demonstrated no statistically
      significant differences for mean bond strengths between LB II and MP. The student
      group recorded a statistically greater bond strength using LB II. The mean
      coefficient of variation of the dentists group showed no statistically
      significant difference between LB II and MP, however that of the students group
      was lower with LB II. When using MP, the dentist group demonstrated a lower
      coefficient of variation than that of the student group. In order to obtain
      optimal bonding performance, or when beginning the use of a new system, the
      operator should be aware of the technique sensitivity of some adhesive systems
      and sensitivity to operator variability.

PMID- 9663063
TI  - Castability of a commercial castable glass ceramics.
AB  - This study was carried out to determine the design and thickness of the cervical
      margin of a castable ceramic restoration from the point of view of its
      castability. Castability of castable ceramics was lower compared to Ag-Pd-Au and
      Co-Cr alloy with the use of the mesh pattern and rod pattern test (p < 0.05). It
      was more dependent on the pattern thickness than alloys (p < 0.05), and perfect
      reproducibility with non-measurable variability could be estimated to reach 1.0
      mm thickness of the original pattern (p < 0.001). Marginal shape was certainly
      more reproducible in a right angle shoulder than in 30, or 45 degree bevels (p <
      0.05). From these results, it is suggested that a right angle shoulder margin
      with 1.0 mm thickness is more suitable to castable glass ceramic restoration than
      any other design.

PMID- 9663064
TI  - Physical properties of resin-modified glass-ionomers.
AB  - The physical properties and shear bond strength of two resin-modified glass
      ionomers: RMGIs (FJL and VT) and as a control, a conventional glass-ionomer: CGI
      (FJ), were evaluated. Ninety percent of the setting shrinkage under dry
      conditions and nominal hygroscopic expansion in water during 360 h occurred
      within the first 24 h. The nominal hygroscopic expansion of CGI was 0.38% while
      the RMGIs demonstrated over 1%, but considering the setting shrinkage the total
      hygroscopic expansion of CGI and the RMGIs were over 7 times and about 2.5 times,
      respectively. The thermal expansion of the RMGIs after water immersion was
      greater than that under dry condition. In contrast, FJ demonstrated expansion
      less than under dry condition. There was no significant difference between FJL
      and VT (P < 0.05) as regard water absorption. The shear bond strength of the
      RMGIs to enamel and dentin were superior to FJ, except for VT to dentin.

PMID- 9663065
TI  - Flexural properties and swelling after storage in water of polyacid-modified
      composite resin (compomer).
AB  - The flexural properties, flexural strength, flexural modulus and modulus of
      resilience, of four commercially available compomers, and one resin-modified
      glass ionomer cement and one microfilled resin comosite (as controls) immediately
      after light-activation and after 1 week of water storage were tested to assess
      the mechanical properties. The water swelling after storage in water was also
      tested to assess the characteristics in water of compomers. The flexural test
      showed compomers to be statistically stronger and more resilient than the resin
      modified glass ionomer cement or the microfilled composite, when tested
      immediately after light-activation and after 1 week of water storage. Water
      swelling of compomers was statistically less than the resin-modified glass
      ionomer cement after 1 week of water storage.

PMID- 9663066
TI  - 2-HEMA-free dentin bonding system to prevent contraction gap.
AB  - The effects of 2-hydroxyethyl methacrylate (2-HEMA) both in the primer and in the
      commercial dentin bonding agent on the efficacy of the dentin bonding system was
      evaluated by measuring the polymerization contraction gap width of a commercial
      resin composite restored in a cylindrical dentin cavity prepared in an extracted
      human molar. Contraction gap formation was prevented in the group of the EDTA
      conditioning followed by glyceryl mono-methacrylate, ethylene glycol and 1,6
      hexanediol priming regardless of the 2-HEMA content in the dentin bonding agent
      containing 10-methacryloxydecyl dihydrogen phosphate. However, gap formation
      could not be prevented completely by the 2-HEMA priming. Therefore, it was
      possible to conclude that 2-HEMA was neither essential in the primer nor in the
      dentin bonding agent because of its low bonding efficacy and the resulting side
      effects on skin tissue as a delayed allergic reaction.

PMID- 9663067
TI  - Reevaluating hand creams and gloves.

PMID- 9663068
TI  - Guidelines for antibiotic prophylaxis for dental patients with joint
      replacements.

PMID- 9663069
TI  - Professional conduct: when patient requests exceed the boundaries of dental care.
AB  - This discussion began with a question regarding the possibility of defining the
      elements of unprofessional conduct. It is likely that the many elements that may
      be intrinsic to this definition are, in part, temporally situated--that is,
      unprofessional behavior is defined somewhat differently today than in 1940. The
      three cases presented underscore this point. It is not likely that dentists of
      two or three decades ago were confronted with patients desiring pierced tongues,
      radio stations that saw dental offices as ideal participants in publicity stunts,
      or individuals admitting their dentist was an instrument of erotic pleasure.
      Despite this dynamic nature of new challenges to professional conduct, many
      elements are constant. Certainly the ethical obligations of beneficence,
      nonmalficence, respect for autonomy, and justice have remained since the time of
      Galen. We have proposed that one modern-day element of defining professional
      conduct is the performance of a professional action for a nonprofessional
      purpose. These types of actions can be harmful to patients and embarrassing to
      the profession. Finally, it is likely that the dentist who cooperates in any of
      the scenarios presented could be held to violation of malpractice standards
      and/or be reprimanded by state dental boards. In addition to these legal
      entanglements, it is clear that knowingly and willingly participating in any of
      the presented cases comprises unethical behavior.

PMID- 9663070
TI  - Porcelain laminate veneers: Part I.

PMID- 9663071
TI  - Diseases of the maxillary sinus.
AB  - Dentists often encounter patients whose signs and symptoms are not related to any
      dental disease, but rather originate in the maxillary sinuses. To distinguish
      when dental care is appropriate, dentists must be familiar with the anatomic,
      physiologic, clinical, and radiographic aspects of the maxillary sinuses.

PMID- 9663072
TI  - Combining chemical agents and techniques to remove intrinsic stains from vital
      teeth.
AB  - Hydrochloric acid, hydrogen peroxide, and carbamide peroxide are chemical agents
      currently used to remove a variety of intrinsic stains from vital teeth. Because
      none of these agents is effective in treating all tooth discolorations,
      approaches that use combinations of the agents can be helpful in extending the
      range of their effectiveness. Selection of the appropriate chemical stain
      removing agent is discussed and situations in which a combination of agents and
      techniques have proved to be more successful than a single agent approach are
      described.

PMID- 9663073
TI  - Success with sealants.
AB  - Specific clinical techniques and practice philosophies are suggested to
      facilitate success with sealants when used by the private practice restorative
      dentist. Although sealants have proven successful in academic and not-for-profit
      environments, this has not always transferred to the private sector. Methods and
      materials, together with economic realities, are all discussed and shortcuts that
      may lead to clinical failures are noted.

PMID- 9663074
TI  - Diagnosis and treatment of pediatric maxillofacial infections.
AB  - Infections of the head and neck are very common in children. Determination of the
      primary etiologic site and organisms responsible for the infection can be
      difficult, because of the close proximity of the skin, teeth, salivary glands,
      sinuses, and eustachian tubes. The bacterial flora and site of origin of an
      infection may vary and should be determined so that the most effective treatment
      regime can be initiated.

PMID- 9663075
TI  - Two-year retention and caries rates of UltraSeal XT and FluoroShield light-cured
      pit and fissure sealants.
AB  - The purpose of this study was to evaluate the long-term retention and effect on
      caries rates of pit and fissure sealants containing fluoride (UltraSeal XT and
      FluoroShield). These sealants were placed in vivo on opposite sides of the arch
      in adolescent patients in a private practice. A total of 470 sealants were placed
      on permanent molars and premolars. After two years, 74.3 percent of the sample
      was available for recall. The total retention rate (Category A) was 96.3 percent
      for UltraSeal XT and 91.4 percent for FluoroShield. There were no new pit and
      fissure carious lesions over the two years of the study. The results for the
      UltraSeal XT is the highest retention rate yet documented.

PMID- 9663076
TI  - Impact of imported beverages on fluoridated and nonfluoridated communities.
AB  - In order to compare the effect of beverages "imported" from nearby communities on
      the fluoride intake of a fluoridated community with that of a nonfluoridated
      community, 45 different carbonated and juice drinks were sampled from Houston
      (fluoridated) and San Antonio (nonfluoridated) and examined for their fluoride
      concentrations. In spite of the fact that an individual lives in a low fluoride
      community, the risk of fluorosis exists through fluoride consumption in beverages
      as well as from the water supply and fluoride therapy. It is therefore important
      for dental practitioners to carefully evaluate their patients' entire fluoride
      exposure before prescribing fluoride supplements.

PMID- 9663077
TI  - Frenotomy and keratinized tissue augmentation.
AB  - Aberrant frenula can be an important etiological factor in progressive gingival
      recession. When separating or removing frenula, augmentation with keratinized
      tissue is the treatment of choice in most circumstances. A case is described as a
      mandibular labial frenotomy in combination with a free gingival graft.

PMID- 9663078
TI  - Provisional restorations and patient satisfaction.
AB  - This case report explains the usefulness of a provisional restoration. The
      benefits are that modifications to improve function and esthetics can be made as
      required, and the patient's wishes can be fulfilled as treatment progresses.

PMID- 9663079
TI  - The likelihood of finding occult histopathology in routine third molar
      extractions.
AB  - Patients had their third molars extracted for reasons unrelated to concerns about
      the presence of pathologic entities. The preoperative differential diagnosis for
      a pericoronal radiolucent lesion was hyperplastic follicle, dentigerous cyst,
      odontogenic keratocyst, and remotely, ameloblastoma. The study involved 42
      patients with 101 bony or soft tissue impacted teeth. The most significant
      microscopic histopathology observed was dentigerous cysts. Of the 101 teeth
      evaluated, 46 (45.5 percent) were dentigerous cysts. The male to female ratio was
      1:1, and the average age was 23.3 years. Frequently, a pericoronal radiolucent
      width of 2.0 mm on the pantomograph is associated with the presence of
      microscopic histopathology. The range of widths of the radiolucency associated
      with the dentigerous cysts in the present was 0.1 to 3.0 mm with 33 (72 percent)
      displaying a radiolucent widths of 1.0 mm. In the present study, dentigerous
      cysts were frequently observed, and aggressive histopathologic entities were not
      identified.

PMID- 9663080
TI  - Dental practices that aid the general practitioner and forensic dentist.
AB  - There are practices that improve the efficiency of a general dentistry office and
      may aid a forensic dentist in making an identification. These practices include
      maintaining current dental charts, using the accepted post-mortem charting
      nomenclature, and maintaining quality radiographs as well as complete and legible
      progress notes.

PMID- 9663081
TI  - Chemically dependent doctors.
AB  - Overcoming denial and admitting to having a chemical dependency problem is a
      hurdle that is extraordinarily difficult for anyone to handle without
      professional assistance. Addicted health care professionals often become even
      more deeply enmeshed in denial of their problem. They refuse help because they
      see themselves as educated beyond the level of those who are attempting to help
      them, and because they fear professional humiliation. Dental professionals who
      become aware of a colleague's chemical dependence, have an ethical duty to
      intervene in a constructive way. Reporting to a dental society wellness committee
      will accomplish this goal while protecting patients, the profession, the addicted
      provider, and the provider's family. Nonetheless, assisting chemically dependent
      colleagues to seek treatment can be an enormous burden. Thus, the dental
      hygienist in the case presented has few choices. She clearly has sufficient
      evidence of the dentist's chemical dependency problem and, ethically, she must
      act to prevent harm to patients. If a wellness program is available, it will help
      her. However, she should not expect gratitude from the dentist at the time of her
      intervention. Addicted persons rarely thank those who try to help them until much
      later and whistle-blowers are rarely appreciated. As is often the case, doing the
      right thing may be a challenge that risks losing a relationship or, as in the
      case presented, a job.

PMID- 9663082
TI  - Choosing an esthetic dental material in 1997.

PMID- 9663083
TI  - Requirements of an impression material for fixed prostheses.
AB  - This article reviews the clinical and laboratory steps in taking impressions for
      creating fixed prostheses. Recommendations for selecting impression materials and
      techniques for using them are discussed. Common problems associated with
      impressions, and their possible causes, are also included.

PMID- 9663084
TI  - The dental materials "revolution": a new health problem?

PMID- 9663085
TI  - Orthodontic management of long face syndrome.
AB  - Management of the vertical dimension of occlusion is one of the most difficult
      aspects of orthodontic therapy. Patients with long face syndrome are prone to
      develop more severe symptoms during orthodontic treatment. This article describes
      a cephalometric measurement (the MM angle), which is useful in the diagnosis of
      long face syndrome. It also gives treatment options designed to minimize the
      expression of long face syndrome characteristics.

PMID- 9663086
TI  - Pre-eruptive intracoronal lesion of a mandibular first molar.
AB  - A patient developed an acute apical abscess on a mandibular first molar with an
      intact occlusal sealant. Radiographs reveal no typical patterns of decay on
      occlusal or proximal surfaces. An unusual lesion within dentin and an apparent
      extension from it to the external tooth surface are visible on films at the time
      of onset of symptoms as well as prior to eruption. Possible explanations for the
      lesion and its progression are discussed.

PMID- 9663087
TI  - The peripheral giant cell granuloma.
AB  - A peripheral giant cell granuloma can be seen as a pedunculated or broad-based
      lesion. Such lesions occur after age 20 years, with 50 percent of patients 40 to
      59 years old. Frequently, there is a history of trauma to the region.

PMID- 9663088
TI  - Growth considerations in planning treatment of avulsion in an adolescent.
AB  - Reimplantation failure of avulsed anterior teeth in an adolescent patient
      requires removal of the attempted-reimplanted teeth and consideration of several
      restorative options. These options may include a removable partial denture, as
      well as a transitional bridge or permanent fixed prosthesis. In all cases, the
      potential effects of the adolescent's expected amount and directions of maxillary
      and mandibular growth must be considered. A case is presented examining how
      maxillary growth may affect the restorative treatment options for avulsed
      anterior teeth replacement for an adolescent boy. Unfortunately, the patient and
      family were unable to complete treatment due to financial considerations.
      Consequently, the case presented here is submitted as a treatment planning
      exercise.

PMID- 9663089
TI  - Dens invaginatus type III in a mandibular premolar.
AB  - Dens invaginatus is a developmental malformation of teeth that frequently
      provides a route for bacterial infection of the dental pulp. It is most commonly
      seen in the maxillary lateral incisor. This case report describes a Type III dens
      invaginatus of the mandibular first premolar, with associated acute apical
      periodontitis. The invagination was treated by endodontic instrumentation and
      obturation, followed by coronal restoration using a glass ionomer base, and an
      occlusal composite resin. The pulp of the tooth tested vital upon presentation,
      and remained vital throughout treatment. Practitioners are reminded to carefully
      evaluate teeth with dens invaginatus for the possibility of maintaining pulp
      vitality.

PMID- 9663090
TI  - Implant placement and simultaneous peri-implant bone grafting using a micro
      titanium mesh for graft stabilization.
AB  - This article reports the surgical technique and outcome of simultaneous bone
      grafting and implant placement. A new treatment philosophy different than the
      principle of guided bone regeneration is presented. The technique is
      characterized by grafting autogenous bone into a peri-implant bone defect rather
      than by regenerating bone in a secluded space. Stabilization of the autogenous
      bone graft is achieved with a micro titanium mesh. The study sample comprised 10
      implant sites in six patients. All sites were successfully treated, and
      postoperative healing was uneventful. The autogenous bone grafts demonstrated
      perfect integration upon reevaluation when the implants were recovered. The micro
      titanium mesh proved to be highly biocompatible, exhibited excellent mechanical
      properties, and avoided graft displacement and contour collapse.

PMID- 9663091
TI  - Evaluation of a bioabsorbable physical barrier for guided bone regeneration. Part
      I. Material alone.
AB  - This study evaluates a prototype bioabsorbable physical barrier material for
      guided bone regeneration. Nonspacemaking dehiscence-type defects were surgically
      created in the right and left mandibles of six adult dogs. Each animal received
      six root-form threaded titanium implants. The osseous defects were randomized to
      receive treatment by either the prototype bioabsorbable barrier composed of a
      copolymer of lactide and glycolide, an expanded polytetrafluoroethylene
      nonresorbable barrier, or no barrier (control), Clinical and histologic results
      after 3.5 months of wound healing indicated that exposed threads were covered
      when treated with the expanded polytetrafluoroethylene barrier. Minimal thread
      coverage was evident with the bioabsorbable barrier and the control.

PMID- 9663092
TI  - Evaluation of a bioabsorbable physical barrier for guided bone regeneration. Part
      II. Material and a bone replacement graft.
AB  - Part I of the evaluation of a prototype bioabsorbable physical barrier composed
      of a copolymer of lactide and glycolide for treatment of bone defects in the
      guided bone regeneration procedure indicated that the prototype bioabsorbable
      physical barrier did not possess sufficient spacemaking characteristics to
      prevent collapse of the barrier into the defect or against the threads of the
      titanium implants. The purpose of Part II was to evaluate this bioabsorbable
      physical barrier in combination with a supporting material to prevent barrier
      collapse. Posterior mandibular teeth in three dogs were extracted and allowed to
      heal for 3 months. This produced localized alveolar ridge defects with a narrow
      buccolingual width. Six titanium threaded implants were placed in the right and
      left mandibles of each dog so that nonspacemaking dehiscencetype defects were
      produced. Two defects in each animal were randomly treated with the prototype
      bioabsorbable physical barrier and decalcified freeze-dried bone allograft; two
      defects were treated with a nonbioabsorbable expanded polytetrafluoroethylene
      barrier with decalcified freeze-dried bone allograft; and one defect each was
      treated with prototype bioabsorbable physical barrier alone or by flap access
      with no barrier or bone replacement graft. The results demonstrated that both the
      bioabsorbable and the nonbioabsorbable barrier combined with decalcified freeze
      dried bone allograft produce comparable amounts of new bone with percent bone-to
      implant contact, height, width, and area. Defects treated with the prototype
      bioabsorbable physical barrier alone or no barrier demonstrated unfavorable
      results. It is suggested that a bone replacement graft is indicated when treating
      defects with a nonspacemaking morphology.

PMID- 9663093
TI  - The bone growing chamber: a new model to investigate spontaneous and guided bone
      regeneration of artificial defects in the human jawbone.
AB  - Spontaneous bone repair and regeneration of jawbone defects have been
      insufficiently studied in the dental literature. The present study analyzes a new
      human model designed to evaluate the basis for spontaneous bone regeneration in
      human jawbones. Hollow titanium cylinders, termed "bone growing chambers," were
      prepared with commercially pure titanium. Ten volunteers undergoing routine
      implant surgery were enlisted. A properly calibrated drill was used to prepare
      the bone-growing-chamber bed. The bone growing chamber was inserted inside the
      bone defect, and care was taken to submerge the cylinder at the level of the bone
      crest. After an adequate healing period, the bone growing chambers were retrieved
      with a small quantity of peripheral bone using a calibrated trephine bur. The
      retrieved specimens were processed to obtain thin undecalcified ground sections.
      The stable bone growing chambers showed bone tissue inside the growing space. The
      maturity of the regenerated bone was related to the time of removal. The bone
      growing chamber provides a well-defined space that is easy to prepare and to
      retrieve; its dimensions are always identical and it allows quantitative
      measurements of bone regeneration inside the chamber space.

PMID- 9663094
TI  - A minimally invasive surgical approach for periodontal bone grafting.
AB  - The term "minimally invasive surgery" has described the use of a surgical opening
      that is smaller than that routinely used to perform similar surgical procedures.
      A periodontal minimally invasive surgery technique for the placement of bone
      grafts in periodontal defects is described. The data from 10 consecutive patients
      on a routine supportive periodontal therapy schedule are presented. The mean
      healing time of the bone graft sites was 25.1 months, the mean probing depth
      reduction was 4.1 mm, and the mean attachment gain was 4.2 mm. Bone grafting
      using minimally invasive surgery appears to give results that are similar to
      results reported using other techniques. Minimally invasive surgery may have the
      advantage of better retention of graft material and maintenance of tissue height.
      Patient acceptance of surgical treatment recommendations may be higher because of
      the perception that minimally invasive surgery represents less surgery.

PMID- 9663095
TI  - Scanning electron microscopy of the root surface texture of extracted
      periodontally diseased teeth following various etching and chelating regimens.
AB  - Scanning electron microscopy of root surfaces that had been ultrasonically scaled
      and subjected to various conditioning regimens revealed the presence of two
      distinct types of cracks: extensive cracks, presumed to have been caused by
      drying before and during sputter-coating procedures; and smaller cracks that
      reflected the pattern of the irregular underlying dentin. Both etching and
      chelating agents appear to cause demineralization of the interfacial layer
      between cementum and dentin, causing a "peeling off" of cementum and exposure of
      the underlying dentin. The results suggest that burnishing the scaled root
      surface with either saline or any of the etching or chelating agents for at least
      10 seconds, followed by soaking the cementum in 8% ethylenediaminetetraacetic
      acid for about 40 seconds, achieved a root surface that might be regarded as
      optimal for regeneration of periodontal tissues.

PMID- 9663096
TI  - Implant periapical lesions: clinical, histologic, and histochemical aspects. A
      case report.
AB  - A new entity, the "implant periapical lesion," has recently been described. The
      etiology of this condition could be attributed to overheating of the bone,
      overloading of the implant, presence of a pre-existing infection or of residual
      root particles and foreign bodies in the bone, implant contamination during
      production or during insertion, or placement of the implant in an infected
      maxillary sinus. In this report, a titanium plasma-sprayed implant had been
      inserted into the mandible of a 53-year-old patient; after 5 months a fistula
      developed and periapical radiography showed a large radiolucent image around the
      apical portion of the implant. The implant was removed, and histologic
      examination showed necrotic bone and an inflammatory infiltrate inside the hollow
      portion of the implant. The etiology of the implant failure in this instance
      could be related to a fracture and vascular impairment of the bone inside the
      implant during insertion, to external contamination of the implant, or to the
      poor bone quality of the implant site.

PMID- 9663097
TI  - Guided tissue regeneration in a combined periodontal and orthodontic treatment: a
      case report.
AB  - Periodontal defects in adolescents or young adults are often an incidental
      finding within an orthodontic treatment. Most of these patients suffer from a
      special form of periodontal disease: juvenile periodontitis. Guided tissue
      regeneration offers a technique for long-term therapy in such cases. In the case
      presented in this report, periodontal problems were aggravated by malpositioning
      of the affected teeth. Orthodontic and periodontal treatment enabled the
      correction of malpositioning and regeneration of osseous defects.

PMID- 9663098
TI  - "Perceptions".

PMID- 9663099
TI  - Photodynamic therapy of intracranial tissues: a preclinical comparative study of
      four different photosensitizers.
AB  - OBJECTIVE: The effectiveness of four different photosensitizers for intracranial
      photodynamic therapy (PDT) of normal brain tissues and an intracranial tumor was
      investigated in rabbits, using the photodynamic threshold model. SUMMARY: PDT is
      currently being investigated as an adjuvant treatment to surgical resection
      and/or radio chemotherapy of intracranial neoplasms. While possible neurotoxic
      side effects of the treatment have been noted, only limited preclinical data
      quantifying the response of intracranial normal and tumor tissues following PDT
      are available. MATERIALS AND METHODS: The photodynamic threshold dose values for
      the four photosensitizers, Photofrin, 5-aminolevulinic acid (ALA)-induced
      Protoporphyrin IX (PpIX), Tin Ethyl Etiopurpurin (SnET2), and chloroaluminum
      phthalocyanine (AlClPc), were determined using measured light fluence
      distributions, photosensitizer concentration in tissue, and histologically
      determined extent of necrosis following PDT. These measurements were made in
      normal rabbit brain and in an intracranially-implanted carcinoma (VX2). RESULTS:
      For Photofrin, AlClPc, and SnET2 (in an emulsion delivery vehicle) normal grey
      and white matter were very sensitive to PDT, showing a significantly lower
      threshold dose value than VX2-tumor. For ALA-induced PpIX and SnET2 (in liposome)
      very little or no white matter damage was observed. Additionally, ALA-PpIX showed
      significantly lower concentration in white matter than in cortex and tumor.
      Normal brain structures lacking a blood-brain barrier showed high uptake of all
      photosensitizers and, hence, are at risk of collateral damage during PDT.
      CONCLUSIONS: For clinical PDT of most adult intracranial neoplasms ALA-induced
      PpIX appears to be promising, and SnET2 (liposomal) has potential for selective
      tumor destruction with relative sparing of white matter. Other normal brain
      structures and, for the other photosensitizers, also white matter are at risk of
      collateral damage, if exposed to light during PDT.

PMID- 9663100
TI  - Combined effects of laser irradiation/solution fluoride ion on enamel
      demineralization.
AB  - OBJECTIVE: The effects of CO2 laser irradiation of dental enamel were evaluated
      in enamel demineralization experiments in partially saturated solutions (i.e.,
      solutions containing both calcium and phosphate ions) with and without fluoride
      ions. SUMMARY BACKGROUND DATA: Previous studies had shown that a continuous-wave
      CO2 laser at an energy density of around 130 J/cm2 may induce an increased acid
      resistance in human dental enamel as assessed by exposure to severe
      demineralization conditions (0.1 mol/L acetate buffer, pH 4.5 and ionic strength
      0.5 mol/L). METHODS: Enamel blocks were irradiated with a continuous-wave CO2
      laser at a wavelength of 10.6 microns using energy densities of from 42.5 to
      170.0 J/cm2. The blocks were then exposed to a partially saturated demineralizing
      solution with or without 0.2 ppm fluoride at a temperature of 30 degrees C for 24
      hours. The demineralization was examined both qualitatively by light microscopy
      and quantitatively by microradiography. RESULTS: A comparison between the lased
      and the unlased portions of enamel showed increased acid-resistance with
      increasing laser energy density and, at the highest energy density of 170.0
      J/cm2, there was little or no lesion development in the fluoride-free dissolution
      medium. The demineralization of enamel was reduced dramatically in the presence
      of 0.2 ppm fluoride for both lased and unlased enamel; there was only modest
      lesion development observed for unlased enamel and, at an energy density as low
      as 85.0 J/cm2, the surface of enamel was found to be completely protected.
      CONCLUSIONS: These findings are consistent with the mechanism that laser
      irradiation of dental enamel results in significant reduction of the effective
      solubility of enamel mineral and that there is a significant synergism between
      laser irradiation and solution fluoride with regard to this effect.

PMID- 9663101
TI  - Middle ear laser office ventilation (LOV) with a CO2 laser flashscanner.
AB  - BACKGROUND: Laser assisted ventilation of the middle ear with a defocused laser
      beam has been performed on adults in an office setting without anesthesia.
      OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of a
      highly controlled, char-free CO2 flashscanner technology for the ventilation of
      the middle ear in young children, at this stage under general anesthesia, and
      later without anesthesia. METHODS: A CO2 flashscanning laser, in conjunction with
      a micromanipulator, was used on 21 SOM patients ages 3-7 years old, with followup
      at 2 months. Operating time is approximately 5 minutes. RESULTS: Postoperative
      results show average patency of 2-3 weeks without adverse effects. Of the treated
      patients, 53% did not require a second treatment, whereas 47% still suffered from
      otitis media and needed a second treatment. CONCLUSION: The CO2 flashscanner
      laser technology is effective and safe for middle ear ventilation and provides
      excellent control of the perforation diameter. It is already being performed in
      an office setting with sedation on a limited basis with very promising
      preliminary results. Based on the current study and on 70 additional cases with
      longer interval followup, we anticipate the office technique to become widely
      used in the future.

PMID- 9663102
TI  - Argon laser irradiation effects on sound root surfaces: in vitro scanning
      electron microscopic observations.
AB  - OBJECTIVE: The purpose of this in vitro scanning electron microscopy (SEM) study
      was to evaluate the effect of low fluence (energy density of 11.5 J/cm2 and 100
      J/cm2) argon laser irradiation on the surface morphology of sound root surfaces.
      SUMMARY BACKGROUND DATA: Previous laboratory investigations have shown that argon
      laser irradiation of root surfaces provided a protective effect against in vitro
      cariogenic challenges. METHODS: Root surfaces of extracted human molars were
      sectioned into treatment quarters: 1) mesiobuccal--no treatment control; 2)
      mesiolingual--low fluence argon laser irradiation (0.231 Watts, 11.5 J/cm2 for 10
      seconds); 3) distobuccal--no treatment control; and 4) distolingual--higher
      fluence argon laser irradiation (2.0 Watts, 100 J/cm2 for 10 seconds). All
      surfaces were critical-point dried, coated with platinum and paladium under
      vacuum, and evaluated qualitatively for intactness, surface morphology, surface
      deposits, and porosities in a blinded fashion by scanning electron microscope.
      RESULTS: The argon lased root surfaces demonstrated alterations of root surfaces
      with creation of surface globular particulate material, microporosities, and
      depressions. Both low- and high-fluence lased root surfaces showed areas with
      plaque-like plates with fine punctuate oval particulate material on their
      surfaces. CONCLUSIONS: Argon laser irradiated root surfaces produce surface
      granular to globular deposits that may provide readily mobilized tooth mineral,
      which may become redeposited into the underlying root surface during a cariogenic
      challenge and enhance resistance to caries formation. In addition,
      microporosities created by the argon laser may provide a means for bonding
      fluoride-releasing restorative and preventive materials to root surfaces and
      further improve the root surfaces' ability to resist cariogenic challenges.

PMID- 9663103
TI  - Comparative study about the removal of smear layer by three types of laser
      devices.
AB  - OBJECTIVE: The aim of this study was to analyze the effectiveness of three types
      of laser, argon, Nd:YAG, and Er:YAG, to remove the smear layer from the prepared
      root canal walls in vitro. METHODS: After cleaning and shaping by step-back
      preparation, 32 human extracted maxillary molar teeth were divided randomly into
      four groups. Root canals in group 1 (G1) were unlased and were irrigated by 17%
      EDTA. In group (G2), root canals were irradiated by argon laser at the parameters
      of 1 W, 50 mJ, and 5 Hz. In group 3 (G3) root canals received Nd:YAG laser
      irradiation at 2 W, 200 mJ and 20 Hz. Teeth in group 4 (G4) were irradiated by
      Er:YAG laser at the following parameters: 1 W, 100 mJ and 10 Hz. Then these teeth
      were bisected longitudinally, observed using SEM, and evaluated. RESULTS: The
      middle third of the teeth from G1 showed clean wall surfaces with open dentinal
      tubules. In G2, at the middle third, the smear layer was free and vaporized
      pulpal tissue remnants were observed. In G3, most of the specimens showed very
      clean walls with the smear layer evaporated, melted, fused, and recrystallized in
      both the middle and apical thirds. The walls of G4 revealed the evaporated smear
      layer and open dentinal tubules in the middle and apical thirds. Statistical
      analysis showed significant differences between G1 and G2, G1 and G3, and G1 and
      G4. CONCLUSIONS: These results show that the argon laser and Nd:YAG laser are
      useful to remove the smear layer and that the Er:YAG laser irradiation is the
      most effective to remove the smear layer on root canal walls.

PMID- 9663104
TI  - Percutaneous laser disc decompression in spinal stenosis.
AB  - OBJECTIVE: The authors determined whether percutaneous laser disc decompression
      (PLDD) is an effective treatment for spinal stenosis where bulging or protruding
      discs are a contributing factor. SUMMARY BACKGROUND DATA: Spinal stenosis is
      associated primarily with the middle-aged and elderly patients, its chief symptom
      being low back and/or radicular pain worsened by walking. The condition is
      particularly resistant to conservative measures and to open surgery. PLDD is a
      minimally invasive treatment for intervertebral disc protrusions with low
      morbidity and a high success rate. METHODS: This unblinded study was undertaken
      to determine whether PLDD would alleviate the pain of spinal stenosis in patients
      who also had protruding lumbar discs. Thirty-five patients of both sexes and all
      ages with MRI-documented lumbar spinal stenosis associated with bulging or
      protruding discs were treated with PLDD on an outpatient basis. Pain relief was
      the only parameter followed. Patients were asked to rate their pain immediately
      after treatment, one day later, four weeks later, and at a follow-up ranging from
      five to forty-nine months later. Pain was quantified on a scale of 0-10, with 0
      being a total absence of pain and 10 being severe pain. A score of 0-2 was
      considered excellent, 3-5 good, and 6-10 poor. RESULTS: Excellent results were
      seen in 69% of cases, good in 9%, and poor in 22%. Pain relief immediately after
      treatment always continued through the four weeks and five to forty-nine-month
      follow-ups. CONCLUSIONS: It was our conclusion that PLDD compares favorably with
      open surgery in the treatment of lumbar spinal stenosis that is partially or
      completely due to bulging or protruding discs.

PMID- 9663105
TI  - Hollow waveguide for mid and thermal infrared radiation.
AB  - OBJECTIVE: A novel type of flexible hollow waveguide that facilitates delivery of
      infrared radiation from source to treatment site, and made of polyimide tubes,
      was developed. SUMMARY BACKGROUND DATA: Polyimide tubes with flat internal wall
      and optimal conditions of deposition of guiding metal and dielectric layers were
      used to obtain low losses of radiation and high quality of beam shape. METHODS:
      Etching of the internal wall of polyimide tubes, high reflective metal (silver)
      layers and suitable dielectric layers (index of refraction and thickness) were
      deposited as guiding elements to obtain a waveguide suitable for infrared
      transmission. RESULTS: Polyimide waveguides of very low attenuation (transmission
      of approximately 95% through 1 meter length) beam profile of variable shape as a
      function of bending radius and type of tbe, large delivered radiation power (more
      than 25 Watts), constant delivered power as a function of time (during more than
      250 seconds), and very low divergence of the delivered beam (angle of divergence
      less than 1 degree), were obtained. The polyimide waveguides also are very
      flexible and may be bent to a radius of bending less than 5 cm. The polyimide
      plastic hollow waveguide is suitable for medical applications (chemical and
      physical stable and nontoxic). CONCLUSIONS: The optical and mechanical parameters
      correspond with those requested for applications in medicine for infrared laser
      treatments or radiometric measurements (non-contact thermometry). Waveguides for
      applications in surgery are under preparation.

PMID- 9663106
TI  - Prosthodontics is more than a style of practice; it's a way of life.

PMID- 9663107
TI  - The effect of a carbonated beverage on the wear of human enamel and dental
      ceramics.
AB  - PURPOSE: This study was performed to investigate the effect of a carbonated
      beverage on the wear of human enamel and three dental ceramics: a conventional
      porcelain (Vitadur Alpha), a hydrothermal low-fusing ceramic (Duceram-LFC), and a
      machinable ceramic (Vita Mark II). MATERIALS AND METHODS: Tooth-against-ceramic
      specimens (10 per group) were tested in a wear machine under a load of 40 N, at a
      rate of 80 cycles per minute, and for a total of 25,000 cycles. The test was
      performed in distilled water or with intermittent exposure to a carbonated
      beverage (Coca-Cola). Wear was determined by measuring the height reduction of
      the tooth specimens and the depth of wear track in the ceramic specimens.
      RESULTS: ANOVA revealed a significant difference among the groups for both enamel
      and ceramic wear (p < .001). When tested in water, Alpha porcelain caused
      significantly more enamel wear and also exhibited greater wear than Duceram-LFC
      and Vita Mark II. However, with exposure to the carbonated beverage, the enamel
      wear produced by Duceram-LFC did not differ significantly from that produced by
      Alpha porcelain, and Vita Mark II produced the least amount of enamel wear.
      Overall, exposure to the carbonated beverage significantly increased the enamel
      wear. The wear of Duceram-LFC and Vita Mark II increased with exposure to the
      carbonated beverage. CONCLUSIONS: It was concluded that exposure to the
      carbonated beverage accelerated the enamel wear and decreased the wear resistance
      of Duceram-LFC and Vita Mark II ceramics. Overall, Vita Mark II was shown to be
      the most resistant to wear and also significantly less abrasive than conventional
      Alpha porcelain.

PMID- 9663108
TI  - Die stone disinfection: incorporation of sodium hypochlorite.
AB  - PURPOSE: Previous research has shown that dental gypsum casts may be effectively
      disinfected by the substitution of 10% of the gauging water with 5.25% solution
      of sodium hypochlorite. The purpose of this investigation was to determine the
      properties of gypsum produced from such a solution as opposed to tap water alone.
      MATERIALS AND METHODS: Tests included setting time, compressive strength,
      rigidity, diametral tensile strength, setting expansion, hardness, and detail
      reproduction. RESULTS: The addition of sodium hypochlorite to the gauging water
      resulted in a statistically significant increase in the compressive strength and
      rigidity, and a decrease in setting time (p < or = .5). All other properties
      remained unchanged. CONCLUSIONS: This substitution may be an effective and
      convenient method of disinfecting gypsum casts in the laboratory without
      adversely effecting physical and mechanical properties.

PMID- 9663109
TI  - Effectiveness of adhesive systems for a Co-Cr removable partial denture alloy.
AB  - PURPOSE: In vitro bond strengths of traditional denture base acrylic resin
      (Lucitone 199) to a cobalt-chromium partial denture alloy (J.D. Partial Denture
      Alloy) were tested using two surface pretreatments (sandblast, sandblast and
      electrochemical etch) with three adhesive primers: Lee Metal Primer, Acrylic
      Solder, and CR Inlay cement. A sandblasted group with no primer served as the
      control. MATERIALS AND METHODS: The alloy specimens (8.0-mm bonding diameter)
      were cast and invested to receive a traditional denture base resin after surface
      treatments (sandblasted, and sandblasted-electrochemically etched) and
      application of adhesive primers. The bonded specimens were stored in distilled
      water at 37 degrees C for 24 hours and divided into two groups. The first group
      was debonded in tension on a testing machine at a cross-head speed of 0.05
      cm/min. The second group was subjected to thermocycling of 1,000 cycles and then
      tested for tensile bond strength. The force at which the bond failed was
      recorded, and the bond strength was calculated in megapascals (MPa). The sites of
      bond failure were examined, quantified under (20x) magnification, and recorded.
      Ten specimens were evaluated for each experimental condition for a total of 160
      specimens. Data were analyzed by ANOVA with a factorial design. Means were
      compared by Tukey intervals at the 0.05 significance level. RESULTS: Significant
      differences in bond strength were observed, with primers being the most important
      factor, followed by pretreatment and storage and thermocycling with significant
      interactions. Sandblasted-electrochemically etched alloy with primers more
      effectively enhanced bond strength of the denture base resin to the treated alloy
      than sandblasted alloy with primers. Thermocycling had a greater effect on bond
      strength of the specimens with Acrylic Solder when compared with Lee and CR Inlay
      primers. The highest bond strengths (> or = 18.0 MPa) were observed for the
      conditions involving electrochemical etching and the priming with CR Inlay cement
      (both after 24 hours and thermocycling of 1,000 cycles). For primed specimens,
      the bond failures occurred cohesively within the primers or the denture resin and
      adhesively between the primers and the denture base resin, or between primers and
      alloy. For nonprimed, the bond failures occurred adhesively at the denture base
      resin-metal interface. CONCLUSIONS: Nonprimed specimens (both sandblasted and
      electrochemically etched) had lowest bond strength (0.4 +/- 0.1 MPa; 0.3 +/- 0.4
      MPa). The bond strengths of the primed treated specimens were improved
      significantly. The CR Inlay-treated specimens exhibited the highest bond strength
      (20.6 +/- 6.3 MPa). After thermocycling for 1,000 cycles, the bond strengths of
      the specimens were significantly lower than the bond strengths of the specimens
      after 24 hours.

PMID- 9663110
TI  - A review of preweighed, packaged die stone versus bulk die stone use in a dental
      school.
AB  - PURPOSE: This study compared the quantity of preweighed, packaged die stone use
      to bulk die stone use by dental students. MATERIALS AND METHODS: Starting in
      September 1994, all the bulk die stone was removed from the dental clinic, and
      only preweighed packages of die stone (Silky-Rock, Whip Mix) were available to
      students. At the end of August 1995 and August 1997, the amount of preweighed die
      stone used by the students was determined and compared with the amount of bulk
      die stone (DieKeen, Modern Materials) used during the period of September 1993 to
      August 1994. RESULTS: Between September 1994 and August 1997, the students used
      42% less per annum of the preweighed, packaged die stone than the previous annual
      use of bulk die stone. The laboratories were much cleaner when the preweighed
      packages were used, and fewer cleaning staff were required. The environment was
      also cleaner for the laboratory staff, who used to fill the bulk containers with
      gypsum products. CONCLUSIONS: Students used 42% less die stone per annum when
      using the preweighed packages.

PMID- 9663111
TI  - Defining predoctoral prosthodontic curriculum: a workshop sponsored by the
      American College of Prosthodontists and the prosthodontic forum.
AB  - Prosthodontic educators participated in a workshop held at The American College
      of Prosthodontists annual session in Kansas City, MO, in October 1996. Their goal
      was to review elements of the predoctoral prosthodontic curriculum to establish a
      consensus on the levels of expected skill and knowledge. Skill components were
      designated at the competency and exposure levels, while knowledge components were
      designated at the understanding and familiarity levels. The workshop
      recommendations were distributed to American and Canadian dental schools and the
      communities of interest for comments in January 1997. The workshop
      recommendations were reviewed and finalized at the American Association of Dental
      Schools annual meeting in Orlando, FL, in March 1997. The recommendations may be
      used by dental educators to prioritize curricular elements in relation to limited
      time dedicated to the prosthodontic curriculum. Outcomes assessment methods will
      be needed to ensure competency in the new dentist.

PMID- 9663112
TI  - Restoring the edentulous maxilla using an implant-supported, matrix-assisted
      secondary casting.
AB  - The selection of appropriate implant treatment modalities for the edentulous
      maxillary arch is complex. Although many patients are candidates for an implant
      supported removable prosthesis, two major considerations affecting choice of
      treatment type are the amount of residual alveolar bone and soft tissue, and
      cost. A technique is described that employs a cast milled primary bar and a
      secondary casting constructed using a vacuum-formed 0.040-in plastic matrix. The
      secondary casting is intimately adapted to the primary bar and incorporates the
      retentive elements within it. The resulting prosthesis is less expensive than
      comparable designs, and retentive elements are easily replaceable. The technique
      is adaptable to most implant systems. The matrix-assisted secondary casting
      technique provides a design that is esthetic and hygienic. The prosthesis may
      also be easier to insert and remove than implant-supported removable prostheses
      that use plunger- or latch-type retention.

PMID- 9663113
TI  - An alternative technique for mandibular advancement prosthesis fabrication.
AB  - One of the conservative and successful modalities of treatment for obstructive
      sleep apnea is the mandibular advancement prosthesis. This prosthesis engages
      teeth on both dental arches for retention and stability. This article describes a
      technique that allows the fabrication of such a prosthesis in one piece and in a
      single laboratory step. This may be beneficial in reducing the laboratory time
      required for fabrication of such a prosthesis.

PMID- 9663114
TI  - Impression technique for arches requiring both implant and natural tooth
      restorations.
AB  - Implant impression copings reduce access to prepared teeth during the impression
      making process. If the impression copings and teeth are in close proximity, it
      may be difficult to extrude impression material circumferentially around the
      margins of the tooth preparations. A technique is described that allows the
      impressions of the prepared teeth to be made without the implant impression
      copings interfering. The advantages and disadvantages of the technique are
      discussed.

PMID- 9663115
TI  - A simple toothbrush modification for easier implant-supported prosthesis hygiene.
AB  - The lingual aspect of mandibular anterior implant-supported prostheses is often
      difficult to reach for adequate hygiene. The following technique describes
      modification of an end-tufted toothbrush to allow for improved access into to
      difficult-to-reach areas.

PMID- 9663116
TI  - How others view us: gleanings from the literature.

PMID- 9663117
TI  - Severity of localized juvenile periodontitis as related to polymorphonuclear
      chemotaxis and specific microbial isolates.
AB  - The purpose of this study was twofold: (a) to determine if an association exists
      between severity of localized juvenile periodontitis (LJP) and impairment of
      polymorphonuclear leukocyte (PMN) chemotaxis and/or colonization by specific
      microbial isolates; (b) to determine if the number of specific microbial
      isolates, i.e., Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis,
      Prevotella intermedia, Fusobacterium nucleatum, Eikenella corrodens, and
      Campylobacter rectus correlates to clinical severity of sites with LJP. Thirty
      six first molars in nine subjects with LJP were examined. A clinical severity
      score was computed based on attachment level and vertical bone loss. The mean
      score of the four sites was designated as the clinical severity score for each
      subject. A DNA probe was used to quantitate colonization by A.
      actinomycetemcomitans, P. gingivalis, P. intermedia, F. nucleatum, E. corrodens,
      and C. rectus. The chemotaxis of isolated peripheral blood PMNs was measured in
      Boyden chambers using the leading front technique. It was found that the clinical
      severity score ranged from 7.8 for mild involvement to 32.5 for severe LJP. The
      chemotaxis result for each patient (micron/90 min) was expressed as a percentage
      of the value for a paired healthy control and ranged from 40% to 104%. Four of
      the nine subjects had chemotaxis values less than 70% of control. Linear
      regression analysis showed: (a) no significant correlation between PMN chemotaxis
      and severity of LJP in subjects (r = .14); (b) a significant correlation (r =
      0.43) between severe sites with LJP and number of specific microbial isolates.
      Sites with severe LJP had present at least five different microbial isolates as
      compared with non-severe sites (P < .05). No particular trend of colonization by
      periodontopathogens was seen in non-severe sites. Further, severe sites of LJP
      displayed a statistically significant greater colonization by P. intermedia, E.
      corrodens, and C. rectus than did non-severe sites (P < .05). It may be concluded
      that neither the degree of PMN chemotactic impairment nor A.
      actinomycetemcomitans is a reliable indicator of the severity of LJP.

PMID- 9663118
TI  - Clinical evaluation of free connective tissue grafts used to increase the width
      of keratinised gingiva. 1974.

PMID- 9663119
TI  - The traveling tooth-wash vendor. 1883.

PMID- 9663120
TI  - Tooth devitalization via implant placement: a case report.
AB  - This case report documents the devitalization of an adjacent tooth during
      osteotomy preparation for implant placement. The fixtures were placed without
      consulting the patient's dentist. Furthermore, radiographs were not taken during
      stage 1 surgery. The patient started to experience painful symptoms 1 month after
      fixture placement, and a radiograph was taken at that time. It revealed
      periapical pathology on the mandibular left canine, through which the base of the
      implant penetrated. This traumatic injury at the tooth's apex undoubtedly caused
      its devitalization. Prompt removal of the fixture and endodontic therapy on the
      canine resulted in repair of the osseous site within 3 months.

PMID- 9663121
TI  - The relationship between probing bone loss and standardized radiographic
      analysis.
AB  - This study evaluated the validity of radiographic alveolar bone defect depth
      measurements to direct probing measurements. The study was planned in two parts.
      The first part consisted of the evaluation of artificially prepared defects in
      dry mandibles. These consisted of 3-mm intrabony defects created at the mesial
      aspect of the second mandibular molar and a Class II furcation defect on the
      buccal aspect of the first molar. A total of six standardized periapical
      radiographs with grids were obtained. They were then evaluated by 10 independent
      examiners who recorded the distance between the alveolar crest (AC) or root
      junction (RJ) and base of defect (BD) in the proximal and furcation areas of the
      teeth. Intra- and inter-examiner differences were assessed. Radiographic results
      showed that these measurements overestimated the mean defect depth values within
      0.12 mm in intrabony defects and underestimated within 0.40 mm in Class II
      furcation defects. The differences between the radiographic and direct dry
      mandible defect depth measurements were found to be statistically significant (P
      < .05) with correlation values r = .50 and r = .46, respectively. The clinical
      part of the study included evaluation of 64 preoperative radiographs taken from
      patients who underwent various types of periodontal surgery. Mean clinical bone
      defect depth was found to be 4.20 mm and the mean of the radiographic defect
      depth measurements was found to be 3.92 mm in intrabony defects. In furcation
      defects these values were 3.92 mm and 3.55 mm, respectively. The results revealed
      that (1) a strong correlation existed between the radiographic and clinical
      assessments in both type of defects (r = .85, P < .001), and that (2) the
      difference between the two types of assessment methods was generally within 1 mm
      (58%). It can be concluded that in both dry mandible and clinical studies
      radiographic interpretation of the intrabony and furcation defects showed
      differences from the actual bone defect depths.

PMID- 9663122
TI  - From NANDA to ICNP.

PMID- 9663123
TI  - Drug knowledge is critical.

PMID- 9663124
TI  - Are needle-exchange programs really helpful?

PMID- 9663125
TI  - Procedural pain management.

PMID- 9663126
TI  - Delegation debate.

PMID- 9663127
TI  - Cold facts about epistaxis.

PMID- 9663128
TI  - Interpreting symptoms.

PMID- 9663129
TI  - Depression & your patient.

PMID- 9663130
TI  - Emergency! Circulatory overload secondary to blood transfusion.

PMID- 9663131
TI  - Nursing essentials: skin grafts for patients with burns.

PMID- 9663132
TI  - Cushing's syndrome.

PMID- 9663133
TI  - Facing the challenge of childhood leukemia.

PMID- 9663134
TI  - One day at a time: David's story.

PMID- 9663135
TI  - Sparkling cider.

PMID- 9663136
TI  - Nurses step to forefront of elder care.

PMID- 9663137
TI  - Preventing sports injuries.

PMID- 9663138
TI  - Life as a traveling nurse.

PMID- 9663139
TI  - When an adolescent wants to forgo therapy.

PMID- 9663140
TI  - Protecting our kids from Joe Camel.

PMID- 9663141
TI  - Significance of workplace smoking.

PMID- 9663142
TI  - Are you certain?--uncertainty, health, and safety in contemporary work.

PMID- 9663143
TI  - Nihilism and pragmatism in tuberculosis control.

PMID- 9663144
TI  - What it takes to control tuberculosis.

PMID- 9663145
TI  - Topics for our times: welfare reform and women's health.

PMID- 9663146
TI  - Topics for our times: new health care data--new horizons for public health.

PMID- 9663147
TI  - The case for stronger OSHA enforcement--evidence from evaluation research.

PMID- 9663148
TI  - Lung cancer from passive smoking at work.
AB  - OBJECTIVES: This study was undertaken to determine whether exposure at work to
      environmental tobacco smoke is associated with an increased risk of lung cancer.
      METHODS: Data from 14 studies providing information on lung cancer and exposure
      to environmental tobacco smoke at work were examined. Six quality criteria were
      developed for determining usable data. A meta-analysis was performed to obtain a
      combined risk for those data that met the quality restrictions. RESULTS: Five
      studies met the quality standards. Their combined relative risk was 1.39 (95%
      confidence interval [CI] = 1.15, 1.68) based on 835 lung cancer cases. In various
      meta-analyses prepared by tobacco industry employees or consultants, no increase
      in risk was found. The main reason for this difference is that the earlier
      analysts failed to find errors in 2 underlying studies that resulted in
      overweighting of the odds ratios from those studies, both of which were less than
      unity. CONCLUSIONS: When appropriate cognizance is taken of the quality of data
      inputs, the increase in lung cancer risk from workplace exposure to environmental
      tobacco smoke is about the same as that from household exposure.

PMID- 9663149
TI  - An uncertain future: the health effects of threats to employment security in
      white-collar men and women.
AB  - OBJECTIVES: This study examined changes in the health status of civil servants
      whose employment security was threatened. METHODS: Data were derived from a
      longitudinal cohort of 10,308 men and women, office staff in 20 British civil
      service departments. Physiological measurements, self-reported morbidity, and
      health-related behaviors for 530 members of the department under threat were
      compared with those of 19 other departments, during the period of uncertainty and
      during stable employment 5 years earlier. RESULTS: From a position of advantage
      or no difference at baseline, self-reported morbidity and physiological risk
      factors tended to increase among respondents from the threatened department
      compared with those from other departments. For both sexes, increases were
      significant for body mass index (P < .001) and sleeping 9 or more hours (odds
      ratio [OR] = 1.88; 95% confidence interval [CI] = 1.3, 2.8; P < .01); modest but
      significant increases were seen in ischemia (OR = 1.45; 95% CI = 1.0, 2.1) and
      cholesterol concentration (0.08 mmol/L; 95% CI = 0.01, 0.14). Among women only, a
      significant relative increase in blood pressure (P < .01) was recorded. Over the
      same period health-related behaviors changed little. CONCLUSIONS: Threats to
      employment security have adverse consequences for health status that are
      unexplained by health selection or health-related behaviors.

PMID- 9663150
TI  - Effects of a Dutch work-site wellness-health program: the Brabantia Project.
AB  - OBJECTIVES: This study examined a project designed to improve the health and
      wellness of employees of Brabantia, a Dutch manufacturer of household goods, by
      means of lifestyle changes and changes in working conditions. METHODS: The
      workers at one Brabantia site constituted the experimental group, and the workers
      from two other sites formed the control group. Biomedical variables, lifestyles,
      general stress reactions, and quality of work were measured identically in both
      groups at baseline and 1, 2, and 3 years later. During this period, there was
      continuous registration of absenteeism. RESULTS: The interventions brought about
      favorable short-term changes in terms of health risks, and there were stable
      effects on working conditions (especially decision latitude) and absenteeism.
      CONCLUSIONS: A combination of interventions directed at both lifestyles and the
      work environment can produce extensive and stable effects on health-related
      variables, wellness, and absenteeism.

PMID- 9663151
TI  - The effect of work status on initiation and duration of breast-feeding.
AB  - OBJECTIVES: In this study, longitudinal data are used to examine the effect of
      work status on breast-feeding initiation and duration. METHODS: Mothers from a
      mail panel completed questionnaires during late pregnancy and 10 times in the
      infant's first year. Mother's work status was categorized for initiation by hours
      she expected, before delivery, to work and for duration by hours she worked at
      month 3. Covariates were demographics; parity; medical, delivery, and hospital
      experiences; social support; embarrassment; and health promotion. RESULTS:
      Expecting to work part-time neither decreased nor increased the probability of
      breast-feeding relative to expecting not to work (odds ratios [ORs] = .83 and
      .89, P > .50), but expecting to work full-time decreased the probability of
      breast-feeding (OR = .47, P < .01). Working full-time at 3 months postpartum
      decreased breast-feeding duration by an average of 8.6 weeks (P < .001) relative
      to not working, but part-time work of 4 or fewer hours per day did not affect
      duration, and part-time work of more than 4 hours per day decreased duration less
      than full-time work. CONCLUSION: Part-time work is an effective strategy to help
      mothers combine breast-feeding and employment.

PMID- 9663152
TI  - Occupational skin diseases in Washington State, 1989 through 1993: using workers'
      compensation data to identify cutaneous hazards.
AB  - OBJECTIVES: This study sought to characterize occupational dermatoses and
      cutaneous hazards. METHODS: Workers' compensation claims filed for skin disease
      in the Washington State Fund were analyzed for 1989 through 1993; incidence rates
      for industries and employers were calculated, and cutaneous hazards associated
      with the highest rates were identified. RESULTS: A total of 7445 claims were
      filed for skin disorders, principally contact dermatitis; 675 (9.1%) involved
      more than 3 missed work-days. The rate of accepted skin disorder claims was 1.0
      per 1000 full-time employee-years. The highest incidence rates (4.6 to 30.7
      accepted claims per 1000 full-time employee-years) were in certain manufacturing
      industries (plastics related, concrete products, aircraft parts, sporting goods,
      and boat building), wholesale farm product raw materials, automotive glass
      replacement, and beauty shops. Seven of the 10 employers with the highest
      incidence rates (19.6 to 85.5 accepted claims per 1000 full-time employee-years)
      used fiber-reinforced plastics (composites) and exposed workers to epoxy and
      other resin systems associated with contact dermatitis. CONCLUSIONS: Workers'
      compensation data identify known and emerging workplace cutaneous hazards and
      show promise for targeting prevention efforts.

PMID- 9663153
TI  - Directly observed therapy and treatment completion for tuberculosis in the United
      States: is universal supervised therapy necessary?
AB  - OBJECTIVES: This study examined the relationship between directly observed
      therapy and treatment completion rates in the years before and after infusion of
      federal funding for tuberculosis (TB) control in 1993. METHODS: An ecological
      study of estimated directly observed therapy rates and 12-month treatment
      completion rates from 1990 through 1994 was undertaken for TB control programs in
      all 25 cities and counties across the nation with 100 or more incident TB cases
      in any year from 1990 to 1993. Three cohorts were formed: high treatment
      completion, intermediate completion, and low completion. RESULTS: In 1990, the
      median 12-month treatment completion rate was 80% for the entire study
      population, with a median estimated directly observed therapy rate of 16.8%. By
      1994, those rates had increased to 87% and 49.4%, respectively, and increases
      were shown in all 3 cohorts. CONCLUSIONS: Directly observed therapy has had a
      marked impact on treatment completion rates in jurisdictions with historically
      low rates. But TB treatment completion rates of more than 90% can be attained
      with directly observed therapy rates far lower than those proposed by advocates
      of universal supervised therapy.

PMID- 9663154
TI  - The fall after the rise: Tuberculosis in the United States, 1991 through 1994.
AB  - OBJECTIVES: Factors associated with decreases in tuberculosis cases observed in
      the United States in 1993 and 1994 were analyzed. METHODS: Changes in case counts
      reported to the national surveillance system were evaluated by dividing the
      number of incident cases of TB reported in 1993 and 1994 by the number of cases
      reported in 1991 and 1992 and stratifying these ratios by demographic factors,
      AIDS incidence, and changes in program performance. RESULTS: Case counts
      decreased from 52,956 in 1991 and 1992 to 49,605 in 1993 and 1994 (case count
      ratio = 0.94, 95% confidence interval [CI] = 0.93, 0.95). The decrease, confined
      to US-born patients, was generally associated with AIDS incidence and
      improvements in completion of therapy, conversion of sputum, and increases in the
      number of contacts identified per case. CONCLUSIONS: Recent TB epidemiology
      patterns suggest that improvements in treatment and control activities have
      contributed to the reversal in the resurgence of this disease in US-born persons.
      Continued success in preventing the occurrence of active TB will require
      sustained efforts to ensure appropriate treatment of cases.

PMID- 9663156
TI  - Differences between completers and early dropouts from 2 HIV intervention trials:
      a health belief approach to understanding prevention program attrition.
AB  - OBJECTIVES: The purpose of this study was to identify factors predicting program
      attrition among participants in human immunodeficiency virus (HIV) risk reduction
      trials. METHODS: Participants were gay/bisexual men and severely mentally ill
      adults recruited to take part in HIV risk reduction small-group interventions.
      Program completers were compared with participants who were assessed at baseline
      but then failed to attend any sessions. The health belief model provided a
      framework for selection of possible predictors of program attrition. RESULTS:
      Younger age was associated with early dropout in both samples. Other predictors
      among gay/bisexual men included involvement in an exclusive sexual relationship,
      minority ethnicity, injection drug use, and higher perceived severity of AIDS.
      Severely mentally ill dropouts were less knowledgeable about safer sex methods
      and more likely to hold positive outcome expectancies for condom use.
      CONCLUSIONS: Evaluation of intervention effectiveness among vulnerable population
      segments is threatened if there is selective attrition. Better methods are needed
      to attract and maintain participation in HIV prevention programs. Alternatively,
      wider application of "intention to treat" analysis of intervention outcomes is
      recommended to minimize selection bias due to program dropout.

PMID- 9663155
TI  - Distinct trends in tuberculosis morbidity among foreign-born and US-born persons
      in New Jersey, 1986 through 1995.
AB  - OBJECTIVES: This study evaluated tuberculosis (TB) morbidity trends among foreign
      born and US-born persons. METHODS: TB surveillance data in New Jersey from 1986
      to 1995 were analyzed. RESULTS: The overall TB incidence rate in New Jersey
      declined 15% from 1992 to 1995 after 7 years of increase. However, the incidence
      rate of TB in foreign-born persons increased 75% from 1986 through 1995. The
      proportion of foreign-born persons with TB increased from 20% in 1986 to 37% in
      1995. CONCLUSIONS: TB morbidity among foreign-born persons has continued to
      increase, despite the decline in overall TB morbidity since 1992. Targeted TB
      prevention and control strategies should be developed to effectively reduce TB
      morbidity in foreign-born persons.

PMID- 9663157
TI  - Income inequality and mortality in metropolitan areas of the United States.
AB  - OBJECTIVES: This study examined associations between income inequality and
      mortality in 282 US metropolitan areas. METHODS: Income inequality measures were
      calculated from the 1990 US Census. Mortality was calculated from National Center
      for Health Statistics data and modeled with weighted linear regressions of the
      log age-adjusted rate. RESULTS: Excess mortality between metropolitan areas with
      high and low income inequality ranged from 64.7 to 95.8 deaths per 100,000
      depending on the inequality measure. In age-specific analyses, income inequality
      was most evident for infant mortality and for mortality between ages 15 and 64.
      CONCLUSIONS: Higher income inequality is associated with increased mortality at
      all per capita income levels. Areas with high income inequality and low average
      income had excess mortality of 139.8 deaths per 100,000 compared with areas with
      low inequality and high income. The magnitude of this mortality difference is
      comparable to the combined loss of life from lung cancer, diabetes, motor vehicle
      crashes, human immunodeficiency virus (HIV) infection, suicide, and homicide in
      1995. Given the mortality burden associated with income inequality, public and
      private sector initiatives to reduce economic inequalities should be a high
      priority.

PMID- 9663158
TI  - Social heterogeneity in smoking among African Americans.
AB  - OBJECTIVES: This study assessed the effects of sociodemographic variables on the
      smoking behavior of African Americans. METHODS: Data for 14,397 African-American
      respondents (18-64 years old) to the National Health Interview Survey in the
      years 1990 through 1993 were examined in multivariate models. RESULTS: Age was
      the strongest predictor of smoking, and men were at least 1.75 times as likely as
      women to be smokers (P < .001). CONCLUSIONS: The Year 2000 goal of an 18%
      prevalence rate among African-American adults may not be attained without major
      community interventions focusing on male and middle-aged African Americans.

PMID- 9663159
TI  - Prevalence of cigar use in 22 North American communities: 1989 and 1993.
AB  - OBJECTIVES: This study examined the prevalence rate of and characteristics
      associated with cigar use. METHODS: Data were derived from population-based
      telephone surveys of adults conducted in 22 North American communities in 1989
      and 1993 as part of the National Cancer Institute's Community Intervention Trial
      for Smoking Cessation. RESULTS: Averaged across the 22 communities, the
      prevalence rate of regular cigar use increased 133% from 1989 to 1993. Regular
      cigar use increased in every gender, age, race, income, education, and smoking
      status category. CONCLUSION: These results confirm other data indicating that
      cigar use is increasing.

PMID- 9663160
TI  - Differences in the effect of patients' socioeconomic status on the use of
      invasive cardiovascular procedures across health insurance categories.
AB  - OBJECTIVES: This study evaluated the effect of patients' socioeconomic status on
      use of coronary angiography, bypass grafting, and angioplasty across health
      insurance categories. METHODS: Multiple logistic regression was used to compute
      the odds of receiving each procedure among 206 233 ischemic heart disease
      patients residing in urban California zip codes from 1991 through 1993. RESULTS:
      Residents of high socioeconomic status areas were more likely (odds ratios [ORs]
      = 1.20-1.41) and residents of low socioeconomic status areas were less likely
      (ORs = 0.79-0.84) than residents of middle socioeconomic status areas to undergo
      each procedure. These effects were common among Medicare and health maintenance
      organization patients and uncommon for privately insured and uninsured patients.
      CONCLUSIONS: The effect of socioeconomic status varies across health insurance
      categories.

PMID- 9663161
TI  - Taking chances: problem gamblers and mental health disorders--results from the
      St. Louis Epidemiologic Catchment Area Study.
AB  - OBJECTIVES: This study determined prevalence estimates of problem gambling and
      relationships to other psychiatric and substance use disorders. METHODS: In 1981,
      the Diagnostic Interview Schedule was used to collect epidemiological information
      on problem gambling and other disorders from 3004 adults in St. Louis, Mo.
      RESULTS: The lifetime prevalence of pathological gambling was 0.9%; 46% of those
      surveyed gambled recreationally. Problem gamblers (those reporting at least one
      gambling-related problem) were 9.2% of the sample and were predominately White
      (69%), male (78.2%), and young than nongamblers. They were at increased risk for
      several psychiatric diagnoses, especially for antisocial personality disorder,
      alcoholism, and tobacco dependence. CONCLUSIONS: Clinicians treating alcoholism
      and tobacco dependence may need to screen for problem gambling. Additional
      research in the context of increased gambling opportunities is needed.

PMID- 9663162
TI  - Promoting skin cancer prevention counseling by pharmacists.
AB  - OBJECTIVES: This study evaluated the effects of an intervention on rates of skin
      cancer prevention counseling by pharmacists. METHODS: Fifty-four pharmacies were
      randomly assigned to intervention or control conditions. Intervention consisted
      of training, feedback, and prompts. Counseling rates before and after the
      intervention were obtained from study confederates. RESULTS: At pretest, the
      proportions of control and intervention sites providing counseling at least once
      were 7.4% and 0%, respectively (NS). At posttest, these proportions were 3.7% and
      66.7%, respectively (P < .001). CONCLUSIONS: The results indicated that the
      intervention was successful and that pharmacists can play an important role in
      educating the public about skin cancer prevention strategies.

PMID- 9663163
TI  - A model for the efficient and effective enforcement of tobacco sales laws.

PMID- 9663164
TI  - Reducing the incidence of congenital syphilis in Milwaukee: a public/private
      partnership.

PMID- 9663165
TI  - Integration of service, education, and research in local official public health
      agencies.

PMID- 9663166
TI  - Public health nihilism vs pragmatism: history, politics, and the control of
      tuberculosis.
AB  - Tuberculosis (TB) began to decline in the Western world in the mid- to late
      1800s. In the United States, the disease receded until the mid-1980s, when that
      trend was reversed. Although the TB epidemic in the United States subsided in
      response to public health interventions, it sparked a controversy regarding the
      relative value of targeted public health measures vs broad social reform. That
      controversy, which echoed earlier debates calling for structural reform over
      public health programs, was further strengthened by the historical and
      demographic studies of Thomas McKeown. His influential thesis maintains that
      clinical and primary prevention efforts had little effect on TB mortality. In
      this paper, the historical literature is used to examine whether public health
      had a significant impact on the decline of TB mortality rates in several
      countries. Specifically, the paper describes the arguments for and data affirming
      the efficacy of 2 major public health interventions over time: segregation of
      those infected with pulmonary TB and eradication of bovine TB. This review finds
      support for the hypothesis that public health measures, along with other factors,
      led to falling rates of TB mortality beginning in the late 19th century.

PMID- 9663167
TI  - The effect of cigarette taxes on cigarette consumption.
AB  - OBJECTIVES: This paper reexamines the work of Meier and Licari in a previous
      issue of the Journal. METHODS: The impact of excise taxes on cigarette
      consumption and sales was measured via standard regression analysis. RESULTS: The
      1983 federal tax increase is shown to have an anomalous effect on the regression
      results. When those data are excluded, there is no significant difference between
      state and federal tax increases. Further investigation suggests that firms raised
      cigarette prices substantially in the years surrounding the 1983 federal tax
      increase, which accounts for the relatively large decrease in consumption during
      this period. CONCLUSIONS: Federal excise taxes per se do not appear to be more
      effective than state excise taxes in terms of reducing cigarette consumption. The
      reaction of cigarette firms to government policies appears to be an important
      determinant of the success of antismoking initiatives.

PMID- 9663168
TI  - Methylphenidate in the United States, 1990 through 1995.

PMID- 9663169
TI  - California trends reveal teenage violence myths.

PMID- 9663170
TI  - Medicaid and immunization coverage.

PMID- 9663171
TI  - Salicylate intake and cardiovascular disease.

PMID- 9663172
TI  - Has the US mortality differential by socioeconomic status increased over time?

PMID- 9663173
TI  - Ethical dilemmas in polio eradication.

PMID- 9663174
TI  - The Food and Drug Administration's regulation of drug labeling, advertising, and
      promotion: looking back and looking ahead.

PMID- 9663175
TI  - Urinary excretion of 6 beta-hydroxycortisol as an in vivo marker for CYP3A
      induction: applications and recommendations.
AB  - OBJECTIVE: To evaluate the usefulness of 6 beta-hydroxycortisol as a screen for
      CYP3A induction in early-phase drug development. METHODS: Five groups of 12
      healthy elderly men were randomized to one of five treatment regimens: (1) 600 mg
      rifampin (INN, rifampicin) once daily, (2) placebo once daily, (3) 40 mg SB
      216469 twice a day, (4) 60 mg SB 216469 twice a day, or (5) 40 mg SB 216469 three
      times a day. All medications were taken orally and administered for 7 consecutive
      days. Urine was collected over a 24-hour period for each subject before
      administration and on the last day of administration for each respective regimen
      for measurement of 6 beta-hydroxycortisol and 17-hydroxycorticosteroid
      concentrations. RESULTS: Subjects in the rifampin group had a significant
      increase from predose value in the 24-hour urinary excretion of 6 beta
      hydroxycortisol and the ratio of 6 beta-hydroxycortisol to 17
      hydroxycorticosteroid. All 12 subjects in the rifampin group had increases in 6
      beta-hydroxycortisol excretion, whereas 11 of 12 had an increase in the ratio.
      The placebo and three active treatment groups did not show significant changes in
      either parameter. CONCLUSIONS: Urinary excretion of 6 beta-hydroxycortisol may be
      useful as a screening tool in early-phase development to assess the potential for
      an investigational drug to induce CYP3A.

PMID- 9663176
TI  - Influence of genetic admixture on polymorphisms of drug-metabolizing enzymes:
      analyses of mutations on NAT2 and C gamma P2E1 genes in a mixed Hispanic
      population.
AB  - OBJECTIVES AND STUDY DESIGN: The genetic basis of two polymorphisms of drug- and
      carcinogen-metabolizing enzymes, NAT2 (arylamine N-acetyltransferase-2) and
      CYP2E1 (cytochrome P450 2E1), was studied in genomic deoxyribonucleic acid from
      137 healthy, unrelated subjects from a mixed Nicaraguan population. RESULTS: Six
      point mutations were identified at the coding region of the NAT2 gene, including
      the most common alleles NAT2*4 (41.6%), NAT2*5B (31.4%), and NAT2*6A (16.8%). The
      percentage of carriers of two defective genes was 49.6%. The Nicaraguan
      population studied was in Hardy-Weinberg's disequilibrium for the NAT2 genotype
      (p < 0.01) and the allele frequencies were significantly different from those of
      other populations, being intermediate between those of pure Central American
      Indians and Spanish persons. The frequency of CYP2E1 alleles mutated at the RsaI
      site (c2 allele; 16.5%) was intermediate between that of Spanish white and Asian
      subjects. About 5% of the subjects were homozygous for the c2 allele.
      CONCLUSIONS: These findings indicate a high impact of genetic admixture of
      populations of Asian origin (Central American Indians) and white persons
      (Spaniards) on the genetic polymorphisms studied here and suggest that among
      mixed Hispanics a high heterogeneity of genotypes and phenotypes can be expected
      depending on the degree of genetic admixture of every subgroup. Therefore
      different subgroups of mixed Hispanic subjects can exhibit different results when
      treated with drugs that are inactivated through polymorphic enzymes.

PMID- 9663177
TI  - Pharmacokinetics of morphine-6-glucuronide and its formation from morphine after
      intravenous administration.
AB  - BACKGROUND: Morphine-6-beta-glucuronide is a primary morphine metabolite with
      potent opioid action. However, its low and slow brain permeability eventually
      prevents its central opioid effects after short-term intravenous administration.
      Research is needed to establish whether morphine-6-beta-glucuronide qualifies as
      an analgesic; this study provides the pharmacokinetic bases for such studies.
      METHODS: Plasma concentration-time data of morphine-6-beta-glucuronide and
      morphine obtained from 20 healthy volunteers after short-term intravenous
      administration of either morphine-6-beta-glucuronide or morphine were described
      by a biexponential disposition curve. Disposition parameters of morphine-6-beta
      glucuronide and morphine were estimated by nonlinear regression, and basic
      pharmacokinetic parameters (clearance, volume of distribution at steady state,
      and mean disposition residence time) were derived. A new model of metabolite
      kinetics was applied, and the disposition parameters of morphine and morphine-6
      beta-glucuronide were then used to fit the plasma concentration-time profile of
      morphine-6-beta-glucuronide formed from morphine. Thereby the fraction of
      morphine metabolized to morphine-6-beta-glucuronide and the mean transit time of
      morphine across the site of metabolism were estimated. RESULTS: The extent and
      time course of morphine-6-beta-glucuronide formation from morphine could be well
      described by a parametric model, with a fraction of morphine metabolized to
      morphine-6-beta-glucuronide of 7.55% +/- 1.24% and a mean metabolic transit time
      for morphine to morphine-6-beta-glucuronide of 0.28 +/- 0.21 hour. The underlying
      disposition of morphine and morphine-6-beta-glucuronide was characterized by
      clearance (morphine clearance, 32.7 +/- 6 ml.min-1.kg-1, morphine-6-beta
      glucuronide clearance, 2.2 +/- 0.4 ml.min-1.kg-1), volume of distribution at
      steady state (morphine, 1.8 +/- 0.3 L.hr-1; morphine-6-beta-glucuronide, 0.12 +/-
      0.02 L.hr-1), and mean disposition residence time (morphine, 1.8 +/- 0.4 hours;
      morphine-6-beta-glucuronide, 1.7 +/- 0.4 hours). CONCLUSIONS: The time course of
      morphine-6-beta-glucuronide formation kinetics was analyzed with use of the
      information on the disposition kinetics of both morphine and preformed morphine-6
      beta-glucuronide, which was obtained by separate data fits. The transformation of
      morphine to morphine-6-beta-glucuronide could be described by two parameters
      characterizing the extent and delay of metabolite formation. The results of this
      study will serve as pharmacokinetic bases of future investigations of morphine-6
      beta-glucuronide in human beings.

PMID- 9663178
TI  - Effects of verapamil and diltiazem on the pharmacokinetics and pharmacodynamics
      of buspirone.
AB  - BACKGROUND: Buspirone has an extensive first-pass metabolism, which makes it
      potentially susceptible to drug interactions. The aim of this study was to
      investigate possible interactions of buspirone with verapamil and diltiazem.
      METHODS: In a randomized, placebo-controlled, three-phase crossover study, nine
      healthy volunteers received either 80 mg verapamil, 60 mg diltiazem, or placebo
      orally three times a day. On day 2, after the fifth dose, 10 mg buspirone was
      given orally. Plasma concentrations of buspirone, verapamil, and diltiazem were
      determined up to 18 hours, and the effects of buspirone were measured up to 8
      hours. RESULTS: Verapamil and diltiazem increased the area under the buspirone
      plasma concentration-time curve [AUC (0-infinity)] 3.4-fold (p < 0.001) and 5.5
      fold (p < 0.001), respectively. The peak plasma concentration of buspirone was
      increased 3.4-fold (p < 0.001) and 4.1-fold (p < 0.001) by verapamil and
      diltiazem, respectively. The effect of diltiazem on the AUC(0-infinity) of
      buspirone was significantly (p < 0.05) greater than that of verapamil. The
      elimination half-life of buspirone was not changed by verapamil and diltiazem. Of
      the six pharmacodynamic variables, only the subjective overall drug effect of
      buspirone was significantly increased with verapamil (p < 0.05) and diltiazem (p
      < 0.05). Side effects of buspirone occurred more often (p < 0.05) with diltiazem
      than with placebo. CONCLUSIONS: Both verapamil and diltiazem considerably
      increase plasma buspirone concentrations, probably by inhibiting its CYP3A4
      mediated first-pass metabolism. Thus enhanced effects and side effects of
      buspirone are possible when it is used with verapamil, diltiazem, or other
      inhibitors of CYP3A4.

PMID- 9663179
TI  - Effect of liver impairment on the pharmacokinetics of tolcapone and its
      metabolites.
AB  - OBJECTIVE: To assess the effect of liver impairment on the pharmacokinetics of
      tolcapone and to derive appropriate dose recommendations for patients with this
      disease who are undergoing treatment for Parkinson's disease. STUDY DESIGN: In an
      open, two-way crossover study, 16 patients with moderate liver disease (eight
      with cirrhotic and eight with noncirrhotic liver disease) and eight healthy
      subjects received an oral dose of 200 mg tolcapone and an intravenous dose of 50
      mg tolcapone on separate occasions. The concentrations of total and unbound
      tolcapone and its three major metabolites (tolcapone glucuronide, carboxylic
      acid, and 3-O-methyl metabolite) were assessed in plasma and urine. RESULTS: On
      the basis of total drug concentration, the differences in tolcapone
      pharmacokinetics between the groups were small. However, lower clearance and
      volume of distribution of unbound drug were found among patients with cirrhosis
      than among control subjects. Plasma concentration of the pharmacologically
      inactive glucuronide metabolite was increased among patients with cirrhosis.
      CONCLUSIONS: Half of the recommended dosage of tolcapone should be administered
      to patients with cirrhosis of the liver to maintain the target steady-state
      concentration of unbound drug and to avoid accumulation of tolcapone glucuronide.
      Our data did not indicate a requirement for dosage adjustment in the presence of
      moderate chronic hepatitis.

PMID- 9663180
TI  - The effect of fluconazole on the clinical pharmacokinetics of methadone.
AB  - A randomized, double-blinded, placebo-controlled pharmacokinetic and safety trial
      was conducted to determine the effect of fluconazole on methadone disposition.
      Volunteers receiving methadone maintenance therapy were randomized to receive
      either 200 mg/day oral fluconazole (n = 13) or placebo (n = 12). After 14 days
      there was a 35% average increase in serum methadone area under the curve relative
      to baseline among patients receiving fluconazole (p = 0.0008). At the same time,
      mean serum methadone peak and trough concentrations increased by 27% (p = 0.0076)
      and 48% (p = 0.0023), respectively, and oral clearance of methadone was reduced
      by 24% (p = 0.0007). In contrast, the pharmacokinetics of methadone were
      unaltered in the placebo group. Renal clearance of methadone was not
      significantly affected by fluconazole or placebo therapy. Although exposed to
      increased concentrations of methadone, patients treated with fluconazole did not
      exhibit signs or symptoms of significant narcotic overdose.

PMID- 9663181
TI  - Age, hypertension, and cardiac responses to beta-agonist in humans.
AB  - OBJECTIVES: To evaluate the effects of hypertension on heart rate and left
      ventricular responses to beta-agonist in young and older subjects, as well as the
      modulating effect of the arterial baroreflex on these responses. METHODS:
      Isoproterenol (INN, isoprenaline) alone was infused in 14 young normotensive
      subjects (mean age, 30 +/- 2 years), 18 older normotensive subjects (mean age, 60
      +/- 2 years), 11 young hypertensive subjects (mean age, 36 +/- 1 years), and 17
      older hypertensive subjects (mean age, 59 +/- 1 years); isoproterenol combined
      with ganglionic blockade (trimethaphan [INN, trimetaphan]) was administered to
      eight young normotensive subjects and eight young hypertensive subjects.
      Isoproterenol was infused at three to four incremental rates, each rate for 8
      minutes. Left ventricular responses were assessed by echocardiography. RESULTS:
      Isoproterenol caused similar increases in heart rate in all four groups. With
      ganglionic blockade, heart rate responses were enhanced but were similar in the
      young normotensive and hypertensive subjects. In young subjects, hypertension did
      not affect left ventricular responses to isoproterenol alone, whereas older
      hypertensive subjects showed some blunting of left ventricular responses compared
      with older normotensive subjects. With ganglionic blockade, young hypertensive
      subjects also showed mild blunting of left ventricular responses. CONCLUSION:
      These results show that, in humans, hypertension does not lead to a decrease in
      chronotropic responses to infusion of the beta-agonist isoproterenol and causes
      only a modest decrease in left ventricular responses.

PMID- 9663182
TI  - Effects of nimesulide on constitutive and inducible prostanoid biosynthesis in
      human beings.
AB  - BACKGROUND: The aim of this study was to test the hypothesis that nimesulide, a
      nonsteroidal antiinflammatory drug, or its principal metabolite 4
      hydroxynimesulide, is a selective inhibitor of prostaglandin H synthase-2 in
      human beings. METHODS: Heparinized whole blood samples obtained from healthy
      subjects were incubated with lipopolysaccharide (10 micrograms/ml) for 24 hours
      at 37 degrees C and prostaglandin E2 was measured in plasma as an index of
      monocyte prostaglandin H synthase-2 activity. The production of thromboxane B2 in
      whole blood allowed to clot at 37 degrees C for 60 minutes was assessed as an
      index of platelet prostaglandin H synthase-1 activity. We also measured the
      urinary excretion of 11-dehydrothromboxane B2, prostaglandin E2, 6
      ketoprostaglandin F1 alpha, and thromboxane B2 as in vivo indexes of
      cyclooxygenase activity. All prostanoids were measured by previously validated
      radioimmunoassay techniques. RESULTS: In the whole blood assays in vitro,
      nimesulide was twentyfold more potent than 4-hydroxynimesulide toward the two
      isozymes and both compounds displayed a twentyfold preference for prostaglandin H
      synthase-2 versus prostaglandin H synthase-1. The administration of a single oral
      dose of 100 mg nimesulide to six healthy subjects significantly (p < 0.01)
      reduced monocyte prostaglandin H synthase-2 and prostaglandin H synthase-1
      activity ex vivo by more than 90% and 50%, respectively, up to 6 hours. At 24
      hours, prostaglandin H synthase-2 but not prostaglandin H synthase-1 activity was
      significantly reduced by 49% (p < 0.05). Nimesulide significantly (p < 0.05)
      reduced the urinary excretion of 11-dehydrothromboxane B2 and 6-ketoprostaglandin
      F1 alpha by approximately 30% and 25%, respectively, while not affecting that of
      prostaglandin E2 and thromboxane B2. CONCLUSIONS: Nimesulide is a potent
      inhibitor of human monocyte prostaglandin H synthase-2. However, despite a
      twentyfold selectivity ratio, therapeutic plasma levels of nimesulide are
      sufficiently high to cause detectable inhibition of platelet prostaglandin H
      synthase-1.

PMID- 9663183
TI  - Intermittent dobutamine treatment in patients with chronic refractory congestive
      heart failure: a randomized, double-blind, placebo-controlled study.
AB  - BACKGROUND: Intravenous dobutamine administration improves short-term
      hemodynamics in patients with severe congestive heart failure (CHF). However, the
      clinical benefit of periodic administration remains controversial. OBJECTIVE: To
      evaluate the efficacy of intermittent dobutamine administration in patients with
      refractory CHF. METHODS: Nineteen patients with New York Heart Association class
      III/IV, ischemia-induced CHF participated in this double-blind, placebo
      controlled study. All patients received intravenous dobutamine or placebo over a
      24-hour period every 2 to 3 weeks for 6 months. They were also treated with
      angiotensin-converting enzyme inhibitors, digoxin, and diuretics. The number of
      admissions for CHF and mortality rate were compared. RESULTS: Ten patients
      received dobutamine and nine received placebo. The pretreatment characteristics
      were similar in both groups. No statistically significant difference was observed
      between the number of admissions for CHF (p = 0.11). The median survival after
      enrollment was 7.97 months in the placebo group and 4.6 months in the dobutamine
      group. The Kaplan-Meier survival curves overlay, with no statistically
      significant difference between the treatment arms (p = 0.7). CONCLUSION:
      Intermittent dobutamine infusions in patients with refractory CHF have no effect
      on the need for hospitalization or on survival.

PMID- 9663184
TI  - Serum sickness-like reaction to cefaclor: lack of in vitro cross-reactivity with
      loracarbef.
AB  - OBJECTIVES: A lymphocyte-based in vitro rechallenge technique was used to examine
      the potential for cross-reactivity between loracarbef and cefaclor in children
      who had had adverse reactions to cefaclor. STUDY DESIGN: The study cohort
      included 10 patients (2.2 +/- 1.1 years old) with a serum sickness-like reaction
      to cefaclor, five patients (4.1 +/- 4.6 years old) with immediate-type
      hypersensitivity reactions to the drug, and five patients (1.5 +/- 0.9 years old)
      who had a delayed hypersensitivity reaction to cefaclor without joint involvement
      (i.e., not a serum sickness-like reaction). Peripheral blood mononuclear cells
      were isolated from each patient and were exposed to cefaclor, loracarbef, and the
      metabolites of each generated with phenobarbital-induced murine hepatic
      microsomes. RESULTS: Among patients with cefaclor-associated serum sickness-like
      reactions, lymphocyte killing (expressed as percentage cell kill above baseline)
      in the presence of cefaclor metabolites (83.6% +/- 42.2%) was significantly (p <
      0.02) higher than that observed among the patients with either immediate-type
      (1.1% +/- 2.4%) or delayed hypersensitivity (0%) reactions. In contrast,
      loracarbef did not produce significant in vitro cytotoxicity among any of the
      patient subgroups. Our in vitro evidence was supported at therapeutic rechallenge
      with loracarbef among three children with cefaclor-associated serum sickness-like
      reactions who tolerated a full course of therapy without adverse reactions.
      CONCLUSION: The metabolite-mediated cytotoxicity associated with cefaclor among
      patients who had had serum sickness-like reactions after therapeutic
      administration of the drug was not shared with loracarbef. The extent to which
      the apparent lack of in vitro cross-reactivity between cefaclor and loracarbef
      may be predictive of clinical cross-reactivity is not known.

PMID- 9663185
TI  - Enhanced analgesia and suppression of plasma beta-endorphin by the S(+)-isomer of
      ibuprofen.
AB  - BACKGROUND: Peripheral nociceptive barrage after tissue injury results in acute
      pain and a variety of physiologic responses, including pituitary secretion of
      beta-endorphin. This study evaluated whether administration of the
      pharmacologically active S(+)-isomer of ibuprofen suppresses acute pain and
      plasma beta-endorphin levels in the oral surgery model of acute pain. METHODS:
      Subjects in a single-dose, double-blind, parallel-group study received either 200
      mg S(+)-ibuprofen, 400 mg S(+)-ibuprofen, 400 mg racemic ibuprofen, or placebo.
      Both doses of S(+)-ibuprofen resulted in significantly greater analgesia over the
      first 60 minutes in comparison to racemic ibuprofen and placebo; the 400 mg dose
      of S(+)-ibuprofen also produced greater analgesia at 2 and 3 hours. Plasma levels
      of immunoreactive beta-endorphin decreased over time coincident with the onset of
      analgesia in all groups but were significantly less than placebo after both doses
      of S(+)-ibuprofen from 30 to 120 minutes. CONCLUSIONS: These findings show that,
      compared with racemic ibuprofen, administration of the S(+)-isomer of ibuprofen
      results in faster analgesic onset, greater peak analgesia, similar duration of
      action, and a low incidence of adverse effects, while suppressing nociceptive
      activation of the pituitary-adrenal axis.

PMID- 9663186
TI  - Surgical aspects of splenic disease and lymphoma.

PMID- 9663187
TI  - 25th anniversary of the Mayo School of Health-Related Sciences.

PMID- 9663188
TI  - Accidental needlesticks in the phlebotomy service of the Department of Laboratory
      Medicine and Pathology at Mayo Clinic Rochester.
AB  - OBJECTIVE: To determine the change in accidental needlestick rates in the
      Phlebotomy Service at Mayo Clinic Rochester and to identify safety practices
      implemented from 1983 through 1996. MATERIAL AND METHODS: We retrospectively
      reviewed yearly Phlebotomy Service accidental needlestick rates from 1983 through
      1996. Interviews were conducted with representatives of the Infection Control
      Committee and the management team for the Phlebotomy Service, and minutes of
      meetings of these two groups were reviewed to identify implemented safety
      improvements that may have had an effect on accidental needlestick exposures.
      RESULTS: Accidental needlestick exposures in the Phlebotomy Service declined from
      a high of 1.5/10,000 venipunctures to 0.2/10,000 venipunctures. Several safety
      improvements were made during that time, including the implementation of a one
      handed recapping block, change to single-use evacuated tube holders, increased
      number and improved locations of disposal containers for needles, implementation
      of resheathing needles and retractable capillary puncture devices,
      discontinuation of the practice of changing needles before inoculation of blood
      culture bottles, increased emphasis on safety for new and experienced
      phlebotomists, and improved exposure reporting tools. CONCLUSION: We believe that
      the decrease in our accidental needlestick exposure rate is correlated with the
      changes in education, practices, and products that we have implemented.

PMID- 9663189
TI  - Diastolic ventricular function in children: a Doppler echocardiographic study
      establishing normal values and predictors of increased ventricular end-diastolic
      pressure.
AB  - OBJECTIVE: To extend noninvasive assessment of diastolic cardiac function into
      the pediatric age-group. DESIGN: This study was divided into two phases, the
      first of which was designed to provide an age-appropriate set of normal diastolic
      Doppler echocardiographic data for children and adolescents and the second of
      which was to determine whether these Doppler techniques could be used to identify
      children with increased ventricular end-diastolic pressure (EDP). MATERIAL AND
      METHODS: Complete echocardiographic studies focusing on Doppler variables of
      diastolic ventricular function were performed on 223 normal children. Values
      observed were analyzed for dependence on age, heart rate, and gender. Results
      from the normal group were then compared with Doppler values observed in a group
      of 24 children with catheterization-substantiated increases in ventricular EDP.
      RESULTS: Normal values for the Doppler factors studied vary with both age and
      heart rate. The variables that most confidently distinguished children with
      increased EDP from normal subjects were the ratio of and the difference between
      the durations of pulmonary vein atrial reversal and the mitral A wave. A ratio of
      1.2 or more or a difference of 29 ms or more identified those children with
      increased EDP with sensitivities of 88 and 90% and specificities of 86 and 86%,
      respectively. CONCLUSION: Use of the normal data and the Doppler techniques
      described in this study will allow confident assessment of diastolic function in
      children as well as in adults.

PMID- 9663190
TI  - Occurrence of potentially detrimental temperature alterations in hospitalized
      patients at risk for brain injury.
AB  - OBJECTIVE: To ascertain the incidence and timing of fever in patients at risk for
      temperature modulation of brain injury resulting from ischemia or trauma. DESIGN:
      We retrospectively reviewed the medical records of patients admitted between
      January 1991 and December 1994. MATERIAL AND METHODS: We investigated three
      groups of hospitalized patients considered at risk for ongoing brain injury
      resulting from a prior cerebral insult: successful resuscitation from out-of
      hospital cardiac arrest (CA), subarachnoid hemorrhage (SAH), or traumatic closed
      head injury (CHI). Forty patients per condition were randomly selected from those
      who survived for more than 24 hours after hospital admission. RESULTS: During the
      initial 72 hours of hospitalization, temperature increases to 38 degrees C or
      more (that is, temperatures previously reported to worsen neurologic outcome
      after brain injury) were noted in 83% of patients with CA, 70% of those with SAH,
      and 68% of those with CHI. Within the cohort of febrile patients, 18 to 44% of
      all temperature measurements were 38 degrees C or higher, and the febrile
      episodes occurred randomly throughout the study interval. Fewer than one-eighth
      of the febrile patients received drugs possessing antipyretic properties (such as
      aspirin or acetaminophen) in a dose appropriate to treat fever. No other method
      of temperature control (for example, physical means) was used in any patient. The
      fractions of patients who were dismissed from the hospital with permanent
      neurologic injury were as follows: CA, 20%; SAH, 45%; and CHI, 43%. CONCLUSION:
      In these hospitalized patients at risk for ongoing brain injury, the incidence of
      temperature increases within the range reported to worsen neurologic outcome
      (elevations of 1.0 degree C or more) was very high. The characterization of these
      potentially injurious, randomly occurring, and traditionally undertreated
      temperature increases may have implications for the design of future protocols
      aimed at providing cerebral protection.

PMID- 9663191
TI  - Advanced multiple beam equalization radiography: receiver operating
      characteristic comparison with screen-film chest radiography.
AB  - OBJECTIVE: To test the hypothesis that the advanced multiple beam equalization
      radiography (AMBER) imaging system is superior to conventional chest radiography
      in the demonstration of diffuse infiltrative lung disease, emphysema, pulmonary
      nodules, calcification within nodules, and mediastinal or hilar masses and
      lymphadenopathy. MATERIAL AND METHODS: The study involved 115 patients, each of
      whom underwent chest computed tomography (CT), AMBER, posteroanterior chest
      radiography, and conventional posteroanterior stereoscopic chest radiography (two
      films). All radiographs were obtained with the InSight Thoracic Imaging System.
      Four chest radiologists independently analyzed the 115 AMBER studies, 115
      unpaired single conventional radiographs (a single film from a stereoscopic
      pair), and 115 stereoscopic conventional radiographs (2 films) for the presence
      of diffuse infiltrative lung disease, emphysema, pulmonary nodules, calcification
      within nodules, and mediastinal or hilar masses and lymphadenopathy. For each
      abnormality detected, the radiologists described their level of confidence based
      on a scale of 1 to 5. The 115 CT examinations were interpreted by consensus among
      3 of the chest radiologists. The CT results were considered the standard.
      Receiver operating characteristic (ROC) techniques were used for statistical
      analysis. RESULTS: No statistically significant differences were found with ROC
      techniques between the AMBER system and single or stereoscopic conventional
      screen-film radiography for the abnormalities studied. CONCLUSION: We noted no
      clinically significant difference between AMBER and either single or stereoscopic
      conventional screen-film radiography in this prospective study of 115 patients in
      which CT (performed within 1 week of both radiographic examinations) was the
      standard.

PMID- 9663192
TI  - Stroke in the medical intensive-care unit.
AB  - OBJECTIVE: To analyze the occurrence and outcome of new-onset stroke in
      critically ill patients admitted to a medical intensive-care unit. MATERIAL AND
      METHODS: We reviewed the medical records of patients admitted to the medical
      intensive-care units of two hospitals between 1985 and 1995. In addition,
      computed tomographic scans or scan reports were assessed. RESULTS: We identified
      19 patients with a critical medical illness and a new-onset stroke. Of this study
      group, ischemic stroke developed in 10 patients, 8 of whom were found to have
      bihemispheric infarction. A single territory infarct (the middle cerebral artery
      territory) was noted in two patients. The presumed mechanisms for ischemic stroke
      were disseminated intravascular coagulation (N = 6), cholesterol embolization (N
      = 1), discontinuation of warfarin therapy before an invasive procedure (N = 1),
      septic emboli (N = 1), and cardioversion (N = 1). In nine patients, an
      intracranial hemorrhage developed. Seven patients had a single lobar hematoma,
      whereas multiple intracerebral hematomas were found in two patients. Disseminated
      intravascular coagulation and rupture of a mycotic aneurysm in proven infective
      endocarditis were the most common mechanisms for hemorrhagic stroke. In all
      patients with an ischemic stroke, sudden hemiparesis rapidly progressed to coma.
      In patients with an intracranial hematoma and sudden onset of coma, unilateral
      fixed pupil was the most common initial manifestation. Of the 19 patients, 17
      died and 2 remained severely disabled. CONCLUSION: Coma is a common initial
      manifestation of stroke in patients with a critical medical illness, and
      disseminated intravascular coagulation has a major etiologic role. New-onset
      stroke in the setting of critical medical illness generally is a complication in
      a terminally ill patient.

PMID- 9663193
TI  - Echocardiographically guided pericardiocentesis: evolution and state-of-the-art
      technique.
AB  - Percutaneous pericardiocentesis was introduced during the 19th century and became
      a preferred technique for the management of pericardial effusion by the early
      20th century. Until the era of two-dimensional echocardiographically guided
      pericardiocentesis, however, the procedure was essentially "blind," and serious
      complications were comparatively common, an outcome that resulted in an increased
      preference for surgical solutions. Because two-dimensional echocardiography
      facilitates direct visualization of cardiac structures and adjacent vital organs,
      percutaneous pericardiocentesis can be performed with minimal risk. Since its
      inception in 1979 (19 years ago), the echocardiographically guided
      pericardiocentesis technique has continued to evolve. Important procedural
      adaptations and modifications that optimize safety, simplicity, and patient
      comfort and minimize the recurrence of effusion have been defined and
      incorporated. This technique has been proved to be safe and effective. A detailed
      step-by-step description of the procedure and the necessary precautions to
      optimize success and safety is presented herein.

PMID- 9663194
TI  - Gastric trichobezoar: case report and literature review.
AB  - Bezoars are conglomerates of food or fiber in the alimentary tract of humans and
      certain animals, mainly ruminants. In adults, bezoars are most frequently
      encountered after a gastric operation, but in children, bezoars are associated
      with pica, mental retardation, and coexistent psychiatric pathologic disorders.
      We describe a 4-year-old girl with trichotillomania in whom a gastric
      trichobezoar resulted in failure to gain weight, iron deficiency anemia, and a
      painless epigastric mass. The causes of gastric bezoars are discussed, with
      emphasis on diagnostic considerations, treatment options, and preventive
      measures.

PMID- 9663195
TI  - Association of temporal arteritis, retinal vasculitis, and xanthomatosis with
      multiple myeloma: case report and literature review.
AB  - Bone pain, anemia, renal failure, and paraproteinemia are common manifestations
      in patients with multiple myeloma. In this article, we describe an elderly woman
      with multiple myeloma who had unusual manifestations of cutaneous xanthomatosis,
      temporal arteritis, and retinal vasculitis. The literature of the dermatologic,
      ocular, and rheumatologic manifestations of multiple myeloma is reviewed, and the
      clinical significance of vasculitis in multiple myeloma is discussed.

PMID- 9663196
TI  - Robert Huber--Nobel Prize for chemistry.

PMID- 9663197
TI  - Minimally invasive direct coronary artery bypass--a surgical approach for
      anomalous right coronary artery from left aortic sinus of Valsalva.
AB  - Anomalous origin of the right coronary artery from the left aortic sinus of
      Valsalva, although rare, has been associated with myocardial ischemia and sudden
      death. Methods of surgical correction include ostial reconstruction, excision and
      translocation of the vessel origin, and coronary artery bypass grafting. We
      describe a 39-year-old man with symptoms of myocardial ischemia and an anomalous
      right coronary artery in whom we performed the new, minimally invasive direct
      coronary artery bypass procedure with use of the right internal mammary artery.

PMID- 9663198
TI  - Modern management of prosthetic valve anticoagulation.
AB  - Prosthetic heart valves have been effectively used for many years. Nonetheless,
      they are associated with risks of thrombosis and thromboembolic events, as well
      as anticoagulation-induced bleeding. Substantial changes in anticoagulation
      measurement and dosing have occurred during the past several years. In this
      review, the rationale for anticoagulation in patients with prosthetic heart
      valves, the changes in monitoring and dosing, and the comparison of relevant
      anticoagulation trials are discussed. On the basis of the existing data, new
      recommendations regarding lower anticoagulation levels are offered, utilizing a
      single value goal rather than the traditional therapeutic range. Perioperative
      management of anticoagulation is discussed in light of the available literature,
      and major drug interactions are reviewed.

PMID- 9663199
TI  - Initial evaluation and treatment of infertility in a primary-care setting.
AB  - Infertility is a condition that primary-care physicians frequently encounter. The
      infertility work-up necessitates an understanding of the physiology and anatomy
      of the female and male partners. A systematic work-up can be initiated by a
      primary-care physician. Infertility problems are stressful for the couple, and
      initial assessment by their own physician may help them work through the process
      as well as prepare them if they need to seek the care of a reproductive
      endocrinologist for further assessment or for assisted reproductive techniques.
      Infertility services are expensive and are rarely completely covered by many
      health insurance plans; therefore, a cost-effective evaluation is important. In
      the managed-care environment, a primary-care physician can begin the
      investigation and decide which patients require more advanced assessment and
      treatment. Helping a couple through the stages of an infertility investigation is
      a professionally rewarding experience.

PMID- 9663200
TI  - 49-year-old woman with back pain and loss of consciousness.

PMID- 9663201
TI  - Transurethral electrovaporization of the prostate.
AB  - In this report, we discuss the basic equipment, electrosurgical techniques, and
      achievable effects with electrovaporization of the prostate and summarize follow
      up data in patients who underwent electrovaporization for treatment of
      prostatism. Transurethral electrovaporization of the prostate combines
      electrosurgical vaporization and desiccation to remove obstructive hyperplastic
      prostatic tissue with minimal morbidity. A special electrosurgical modification
      involves a grooved roller electrode with a large surface area and multiple edges
      of contact that allow high current density to be delivered to an extensive area
      of tissue to be vaporized. This device fits standard resectoscopic equipment, and
      its use requires no special skills other than those needed for conventional
      transurethral resection of the prostate. Data analysis on a personal series of
      114 patients with symptomatic benign prostatic hyperplasia who were treated with
      electrovaporization showed a decrease in symptoms, an increase in urinary flow
      rates, and rapid convalescence, similar to results in other published studies.
      Thus, clinical experience with transurethral electrovaporization of the prostate
      has shown efficacy similar to that for transurethral resection of the prostate
      but with considerably reduced morbidity. Extended follow-up of larger numbers of
      patients is needed to assess the durability of this procedure.

PMID- 9663202
TI  - Transurethral needle ablation of the prostate: a minimally invasive treatment for
      symptomatic benign prostatic hyperplasia.
AB  - Transurethral needle ablation of the prostate, a relatively new minimally
      invasive treatment modality for patients with bladder outlet obstruction
      attributable to an enlarged prostate gland, has undergone extensive evaluation by
      numerous investigators worldwide. The results to date indicate that needle
      ablation is safe and effective for relieving symptoms in patients with benign
      prostatic hyperplasia, and the effect has been demonstrated to be durable for at
      least 2 years. Nevertheless, additional investigations with longer follow-up data
      are needed to address the important issues of extended durability (5 to 10 years)
      and biophysiologic mechanism of action. Comparisons between transurethral needle
      ablation of the prostate and transurethral resection of the prostate (TURP) have
      revealed that the subjective and objective measures of response are comparable,
      although TURP has consistently displayed a slight advantage over needle ablation
      for most variables analyzed, except quality of life score. The advantages of
      needle ablation over TURP are (1) performance in the office as an outpatient
      procedure, (2) no need for general or spinal anesthesia, (3) rapid recovery, (4)
      minimal side effects, and (5) one-time intervention. The following disadvantages
      exist with needle ablation: (1) it may not be indicated or effective in patients
      with large prostate glands (75 g or more); (2) no prostate tissue is available
      for histologic evaluation; and (3) no long-term efficacy or re-treatment rate
      data have been published. Overall, the available information indicates that
      transurethral needle ablation is a viable minimally invasive treatment that may
      be applicable in men with moderate to severe bladder outlet obstruction as a
      result of an enlarged prostate gland.

PMID- 9663203
TI  - Phlebotomists at risk.

PMID- 9663204
TI  - Cultural barriers to wellness.

PMID- 9663205
TI  - Stroke thrombolysis and the stroke specialist.

PMID- 9663206
TI  - Induction of prostate-specific antigen expression by synthetic progestins in
      patients with prostate and breast cancer.

PMID- 9663207
TI  - Silicone versus acrylic lenses.

PMID- 9663208
TI  - Corneal endothelial toxicity of topical anesthesia.

PMID- 9663209
TI  - Needling revision of glaucoma drainage device filtering blebs.

PMID- 9663210
TI  - Complications of motility peg placement in hydroxyapatite implants.

PMID- 9663211
TI  - Fungal endophthalmitis.

PMID- 9663212
TI  - In memoriam: A. Edward Maumenee, Jr., MD. 1913-1998.

PMID- 9663213
TI  - Trabeculoplasty, trabeculectomy, and race: is there a difference in response to
      treatment between blacks and whites?

PMID- 9663214
TI  - The Advanced Glaucoma Intervention Study (AGIS): 3. Baseline characteristics of
      black and white patients.
AB  - OBJECTIVE: The purpose of this report is to examine the differences at baseline
      in demographic, medical, and ophthalmic characteristics between blacks and whites
      enrolled in the Advanced Glaucoma Intervention Study (AGIS), a multicenter,
      randomized, clinical trial. DESIGN: Multicenter, randomized, controlled trial.
      PARTICIPANTS: A total of 332 black patients (451 eyes), 249 white patients (325
      eyes), and 10 patients of other races (13 eyes) with open-angle glaucoma that
      could not be controlled by medical therapy alone participated. INTERVENTION:
      There was no intervention performed. METHODS: The investigators compare the
      baseline demographic, medical, and ophthalmic characteristics of black and white
      patients, adjusting the comparisons for age and gender. RESULTS: Blacks in the
      study were younger than whites and had more systemic hypertension and diabetes
      than whites. The visual field defects of blacks on average were substantially
      more severe than those of whites. Intraocular pressures and visual acuity scores
      were similar in the two groups. Blacks were more hyperopic and had relatively
      fewer disk rim hemorrhages than whites. CONCLUSIONS: The findings of the current
      study concur with those of previous clinical studies of open-angle glaucoma that
      visual field defects are more severe in blacks than whites.

PMID- 9663215
TI  - The Advanced Glaucoma Intervention Study (AGIS): 4. Comparison of treatment
      outcomes within race. Seven-year results.
AB  - OBJECTIVE: The purpose of this report is to present separately for black and
      white patients with advanced glaucoma 7-year results of two alternative surgical
      intervention sequences. DESIGN: A randomized controlled trial. PARTICIPANTS: A
      total of 332 black patients (451 eyes), 249 white patients (325 eyes), and 10
      patients of other races (13 eyes) participated. Potential follow-up ranged from 4
      to 7 years. INTERVENTION: Eyes were randomly assigned to either an argon laser
      trabeculoplasty (ALT)-trabeculectomy-trabeculectomy (ATT) sequence or a
      trabeculectomy-ALT-trabeculectomy (TAT) sequence. The second and third
      interventions were offered after failure of the first and second interventions,
      respectively. MAIN OUTCOME MEASURES: Average percent of eyes with decrease of
      visual field (APDVF), average percent of eyes with decrease of visual acuity
      (APDVA), and average percent of eyes with decrease of vision (APDV) are the
      outcome measures. Decrease of visual field (DVF) is an increase from baseline of
      at least 4 points on a glaucoma visual field defect scale ranging from 0 to 20,
      decrease of visual acuity (DVA) is a decrease from baseline of at least 15
      letters (3 lines), and decrease of vision (DV) is the occurrence of either DVF or
      DVA. The averages are of percent decreases observed at 6-month intervals from the
      first 6-month visit to the end of the specified observation period. RESULTS: In
      both black and white patients throughout 7-year follow-up, the mean decrease in
      intraocular pressure was greater in eyes assigned to TAT, and the cumulative
      probability of failure of the first intervention was greater in eyes assigned to
      ATT. In black patients, APDVF, APDVA, and APDV are less for the ATT sequence than
      for the TAT sequence throughout the 7 years. In white patients, APDVF also favors
      the ATT sequence but only for the first year, after which it favors the TAT
      sequence through the seventh year; APDVA also favors the ATT sequence, but the
      ATT-TAT difference progressively diminishes over 7 years; and APDV favors ATT
      over TAT initially, but after 4 years, the advantage switches to and remains with
      TAT. CONCLUSIONS: These data support use of the ATT sequence for all black
      patients. For white patients without life-threatening health problems, the data
      support use of the TAT sequence.

PMID- 9663216
TI  - Factors associated with elevated complication rates after partial-thickness or
      full-thickness glaucoma surgical procedures in the United States during 1994.
AB  - OBJECTIVE: The purpose of the study was to identify factors associated with an
      increased risk of complications after partial-thickness or full-thickness
      glaucoma surgery. DESIGN: A retrospective, cohort analysis. PARTICIPANTS: A total
      of 24,206 Medicare patients who were older than 65 years of age and who were
      enrolled in Medicare in 1994 underwent partial-thickness or full-thickness
      glaucoma surgical procedures in 1994. INTERVENTION: The authors obtained data on
      all glaucoma surgery claims to the Health Care Finance Administration in 1994 and
      analyzed complication rates using hierarchical logistic regression, separately
      smoothing four sets of regression coefficients (state-level effects, systemic and
      ocular diagnoses, prior ocular surgeries, and concomitant ocular surgeries). MAIN
      OUTCOME MEASURE: Patients were classified as having complications if their
      records showed at least one of the following occurrences after surgery: retinal
      detachment repair, endophthalmitis, scleral fistula revision-repair, or
      cyclodestruction. RESULTS: The risk of complications was greater for full
      thickness procedures than for partial-thickness procedures (odds ratio [OR] =
      1.51; 95% confidence interval [CI] = 1.07, 2.12). Compared to glaucoma surgeries
      performed without an additional intraocular procedure, glaucoma surgery with
      prior phacoemulsification (OR = 0.51; 95% CI = 0.35, 0.74) was associated with
      lower complication rates, as was glaucoma surgery with prior argon laser
      trabeculoplasty (OR = 0.62; 95% CI = 0.44, 0.88). A concomitant vitrectomy (OR =
      1.86, 95% CI = 1.35, 2.56) was associated with greater odds of a complication.
      The mean follow-up of subjects was 184 days (standard deviation, +/- 107),
      whereas the mean time to a complication was 49 days (standard deviation, +/- 63).
      CONCLUSION: The risk of an early postoperative complication after full-thickness
      procedures appears to be greater than that after partial-thickness procedures.
      Concomitant intraocular procedures performed in conjunction with glaucoma
      surgery, such as a vitrectomy, can substantially increase the risk of retinal
      detachment repair, endophthalmitis, scleral fistula revision-repair, and/or
      cyclodestruction.

PMID- 9663217
TI  - Angle-closure glaucoma as an initial presentation of systemic lupus
      erythematosus.
AB  - PURPOSE: To study a patient with bilateral uveal effusions and secondary glaucoma
      as an initial manifestation of systemic lupus erythematosus. DESIGN: A case
      report. METHODS: The patient presented with bilateral uveal effusions and angle
      closure glaucoma. A detailed ocular examination with ultrasonography and a
      comprehensive medical evaluation with laboratory testing were performed. RESULTS:
      The ocular examination revealed bilateral uveal effusions with angle-closure and
      elevated intraocular pressures. A systemic evaluation revealed bilateral pleural
      effusions and laboratory values consistent with systemic lupus erythematosus.
      After medical and laser therapy failed to lower the intraocular pressure, partial
      thickness sclerectomies, linear sclerostomies, and choroidal drainage were
      successful in controlling the glaucoma. CONCLUSIONS: Uveal effusion with
      secondary glaucoma can be a presenting sign for systemic lupus erythematosus. If
      antecedent ocular abnormalities are not present, a systemic evaluation is
      warranted in assessing a patient with uveal effusions and secondary angle-closure
      glaucoma. Partial-thickness sclerectomies, linear sclerostomies, and choroidal
      drainage may be effective in lowering intraocular pressure.

PMID- 9663218
TI  - Tonometry in adults and children. A manometric evaluation of pneumatonometry,
      applanation, and TonoPen in vitro and in vivo.
AB  - OBJECTIVE: The purpose of the study was to determine the accuracy of applanation
      tonometry, pneumatonometry, and TonoPen tonometry in adults and children and the
      effect of age on tonometer error. DESIGN: The design was divided into four parts:
      part 1 was prospective and cross-sectional, and parts 2 through 4 were
      prospective, cross-sectional, and masked. PARTICIPANTS: This study contained 72
      patients representing 74 data points. INTERVENTION: Tonometry with simultaneous
      manometry was performed. MAIN OUTCOME MEASURES: Intraocular pressure (i.o.p.) and
      the tonometric estimate of IOP were obtained. RESULTS: The normal pediatric IOP
      follows the line Ta = 0.71 age(years) + 10 up to age 10. Applanation tonometry
      under anesthesia differs from pneumatonometry by an average of -8.6 mmHg and is
      age related by the equation Ta = Tpn + 2.6 log(age) - 10.3. The TonoPen was the
      most accurate instrument for enucleated eyes, and the pneumatonometer was the
      most accurate in anesthetized living eyes. CONCLUSIONS: Applanation tonometry
      markedly underestimated IOP in young eyes. TonoPen tonometry performed well with
      enucleated eyes but was not adequately accurate for clinical use. The
      pneumatonometer performed the best clinically and the best overall.

PMID- 9663219
TI  - Excimer laser treatment of myopic astigmatism. A comparison of three ablation
      programs.
AB  - OBJECTIVE: The purpose of the study was to evaluate the precision, accuracy, and
      safety of three different modes of excimer laser surgery for myopic astigmatism.
      DESIGN: A prospective interventional case series. PARTICIPANTS: A total of 150
      eyes with compound myopic astigmatism were treated. INTERVENTION: Ablation
      programs included the VISX Twenty/Twenty excimer laser using either the
      sequential mode (58 eyes) or the elliptical mode (54 eyes) and the Technolas
      Chiron Keracor 116 hybrid scanning laser (38 eyes). MAIN OUTCOME MEASURES:
      Reduction in cylinder and sphere, vector analysis (polar values), uncorrected
      visual acuity, and best spectacle-corrected visual acuity were evaluated at 1, 6,
      and 12 months. RESULTS: By 12 months, sphere was reduced by 95.1%, 87.7%, and 75%
      in low-astigmatism eyes treated with the VISX sequential, VISX elliptical, and
      Technolas modes, respectively, and by 92.2%, 98%, and 77.6% in high-astigmatism
      eyes. By 12 months, cylinder was reduced by 51.5%, 72.2%, and 36.3% in low
      astigmatism eyes and by 70%, 78%, and 45.6%, respectively, in high-astigmatism
      eyes. Vector analysis showed that the elliptical treatment produced more
      significant reductions in mean polar values than the other two treatments at
      various timepoints. CONCLUSION: These results suggest that the ablation approach
      may influence the clinical result.

PMID- 9663220
TI  - Retreatment after photorefractive keratectomy for low myopia.
AB  - OBJECTIVE: The purpose of the study was to evaluate the results of retreatment
      for low myopia after primary photorefractive keratectomy (PRK). DESIGN: A
      prospective study. PARTICIPANTS: A total of 48 eyes of 37 patients from 566 eyes
      of 331 patients originally treated for myopia of up to -6 diopters (D) were
      studied. INTERVENTION: Photorefractive keratectomy by the Coherent Schwind
      Keratom II excimer laser was performed. MAIN OUTCOME MEASURES: The parameters
      evaluated were visual acuity, refraction, and corneal clarity. RESULTS: Of the
      566 eyes with myopia up to -6 D, 48 eyes (8.5%) required retreatment. The sphere
      (mean +/- standard deviation) was -0.88 +/- 1.24 D before second surgery. At 6
      months, the mean was -0.04 +/- 0.91; at 1 year, it was -0.33 +/- 0.75 D. At 6
      months, 75% of sphere value was within +/- 1 D. The preoperative uncorrected
      visual acuity (UCVA) was 20/200 or worse in 12.8% of eyes and 20/40 or better in
      40.4% of eyes. Six months after reoperation, 20/60 UCVA was obtained in 17.4% of
      eyes. All others (82.6%) had UCVA of 20/40 or better, 26.1% better than 20/20.
      The proportion of eyes with best spectacle-corrected visual acuity better than
      20/20 decreased from 60.0% to 47.1% 6 months after reoperation. Six months after
      reoperation, haze 1 was present in 42.9% and haze 2 in 4.7% of eyes, and in no
      eye was haze worse. CONCLUSION: Retreatment after PRK for low myopia can
      significantly increase UCVA and decrease residual refractive error without
      significant complications.

PMID- 9663221
TI  - Regression and its mechanisms after laser in situ keratomileusis in moderate and
      high myopia.
AB  - OBJECTIVE: The purpose of the study was to evaluate the degree and mechanism of
      regression after laser in situ keratomileusis (LASIK) on moderate to highly
      myopic eyes during the first postoperative year. DESIGN: A prospective, single
      center, clinical trial. PARTICIPANTS: A total of 52 eyes of 38 patients were
      entered in the study; 47 eyes had complete data available at each postoperative
      visit. INTERVENTION: The intervention was LASIK using the microkeratome to create
      an 8.5- to 9.0-mm diameter, 130- to 160-micron-thick flap. A spherical midstromal
      multizone ablation (inner zone, 4.5 mm; outer zone, 5.5-6.0) was then performed
      using the Summit OmniMed excimer laser (Summit Technology, Inc, Waltham, MA). The
      mean preoperative refraction was -14.02 diopters (D). Retreatment for
      undercorrection and regression was performed between postoperative months 3 and 6
      on 13 eyes. MAIN OUTCOME MEASURES: Manifest spherical equivalent, mean central
      corneal power, and central corneal thickness were the parameters measured.
      RESULTS: At 3 months, follow-up data were available on 47 eyes. The mean
      refractive regression was -1.07 D (7.6%) from the first week to the third month.
      During the first postoperative year, the mean regression of manifest spherical
      equivalent (MSE), increase in corneal power, and increase in corneal thickness
      were symmetric in magnitude and time course for the 34 eyes that did not require
      retreatment (-0.96 D, +1.03 D, and 15 microns, respectively). CONCLUSION: Early
      regression of refractive effect after LASIK appears to be a consequence of an
      increase in corneal thickness associated with central corneal steepening. No
      evidence of progressive corneal ectasia was observed during the first year of
      follow-up. Longer follow-up is required to confirm these trends.

PMID- 9663222
TI  - Different suturing techniques variously affect the regularity of postkeratoplasty
      astigmatism.
AB  - OBJECTIVE: This study aimed to determine the effect of various suturing
      techniques on the regularity of postkeratoplasty astigmatism. DESIGN: A
      prospective clinical trial. PARTICIPANTS: Sixty-two consecutive patients
      undergoing penetrating keratoplasty by the same surgeon (MB) participated.
      INTERVENTION: Each patient was assigned to one of four groups according to the
      suturing technique used (a = 16 interrupted 10-0 nylon sutures; b = 2 running 10
      0 nylon sutures, each with 8 bites; c = 2 running 10-0 nylon sutures, each with
      12 bites; d = 2 running 10-0 nylon sutures, each with 16 bites). This was the
      only parameter permitted to be changed in the standard keratoplasty procedure
      used for all cases. Corneal topography was performed 1, 3, and 6 months after
      surgery. The astigmatic patterns seen on the corneal maps then were classified
      into regular (symmetric or asymmetric bowtie patterns) or irregular (distorted
      bowtie, multiaxial, or other patterns). MAIN OUTCOME MEASURES: Regularity of
      postkeratoplasty corneal astigmatism was measured. RESULTS: At all postoperative
      examination times, the percentage of irregular astigmatic patterns was highest in
      group a and lowest in group d (chi-square test: P < 0.005). Groups b and c showed
      intermediate values. The entity of the astigmatic error as measured by the
      simulated K-readings of the topographic maps did not differ significantly in the
      four groups. CONCLUSIONS: A suturing technique using 2 running sutures with 16
      bites each can minimize irregular postkeratoplasty astigmatism as long as sutures
      are in place, when compared with interrupted sutures or double-running sutures of
      less than 16 bites.

PMID- 9663223
TI  - Posterior keratoconus. An expanded classification scheme based on corneal
      topography.
AB  - OBJECTIVE: The purpose of the study was to evaluate corneal changes in posterior
      keratoconus. DESIGN: A retrospective review. RESULTS: Distinct topographic
      patterns were identified. Generalized posterior keratoconus showed uniform
      corneal steepening. Localized central and paracentral posterior keratoconus
      showed corneal steepening, and localized peripheral posterior keratoconus showed
      corneal flattening overlying the area of corneal change. The changes in central
      and paracentral posterior keratoconus appear to progress with an increase in
      patient age. Unilateral disease may have more amblyogenic potential. CONCLUSIONS:
      Posterior keratoconus manifests significant corneal surface alterations. The
      distinct topographic patterns seen probably warrant a further classification of
      localized posterior keratoconus into central-paracentral and peripheral
      varieties.

PMID- 9663224
TI  - A systematic overview of the incidence of posterior capsule opacification.
AB  - OBJECTIVE: Reported rates of posterior capsule opacification (PCO) vary widely
      and are based on various definitions of PCO, varying lengths and intervals of
      follow-up, and the use of different surgical techniques, intraocular lens
      (i.o.l.) designs, and methods of IOL implantation. This study was designed to
      obtain a more precise overall estimate of the incidence of PCO and to explore
      factors that might influence the rate of PCO development. DESIGN: A meta
      analysis. METHODS: Published articles were selected for study based on a
      computerized MEDLINE search of the literature and a manual search of the
      bibliographies of relevant articles. Articles meeting selected inclusion criteria
      were reviewed systematically, and the reported data were abstracted and
      synthesized using the statistical techniques of meta-analysis. MAIN OUTCOME
      MEASURE: Pooled estimates of the proportion of eyes developing PCO at three
      postoperative timepoints--1 year, 3 years, and 5 years--were measured. RESULTS:
      There is significant heterogeneity among published rates of PCO. The overall
      pooled estimates (95% confidence limits) of the incidence of PCO were 11.8% (9.3%
      14.3%) at 1 year, 20.7% (16.6%-24.9%) at 3 years, and 28.4% (18.4%-38.4%) at 5
      years after surgery. There is no evidence of a significant decline in PCO
      incidence during the study period. CONCLUSIONS: Visually significant PCO develops
      in more than 25% of patients undergoing standard extracapsular cataract
      extraction or phacoemulsification with posterior chamber intraocular lens
      implantation over the first 5 years after surgery. Patient characteristics,
      surgical techniques, and differences in research design and reporting may account
      for some of the variability in reported rates. However, no specific factors were
      identified in the authors' analysis. More precise estimates of incidence and
      identification of risk factors for PCO will depend on the development of a
      standardized measurement of PCO and wider adoption of more rigorous study
      methodology.

PMID- 9663225
TI  - Decrease of capsular opacification with adjunctive mitomycin C in combined
      glaucoma and cataract surgery.
AB  - OBJECTIVE: The authors investigated the incidence of capsular opacification
      requiring YAG capsulotomy after primary trabeculectomy combined with
      phacoemulsification and implantation of all polymethylmethacrylate intraocular
      lenses. DESIGN: A prospective randomized study. PARTICIPANTS: One hundred seventy
      four eyes of 174 nonselected patients with primary open-angle glaucoma (POAG)
      were randomized to either no adjunctive mitomycin C (MMC) control group of 93
      eyes of 93 patients) or adjunctive subconjunctival MMC (MMC group of 81 eyes of
      81 patients) during the primary glaucoma triple procedure (PGTP). INTERVENTION:
      Primary glaucoma triple procedure with and without MMC and YAG laser capsulotomy
      for posterior capsular opacification (PCO) was performed. MAIN OUTCOME MEASURES:
      The incidences of YAG capsulotomy for PCO were compared between the control and
      MMC groups and also between the control group and the MMC subgroups (1 minute, 3
      minutes, and 5 minutes of MMC application) using Kaplan-Meier analysis with
      Mantel-Cox log-rank test. Cox proportional hazard regression analysis also was
      performed to identify significant factors affecting capsular opacification.
      RESULTS: The control and MMC groups were similar in preoperative characteristics.
      However, the probability of PCO requiring YAG capsulotomy was significantly lower
      in the MMC group than in the control group (P = 0.004). Among the MMC subgroups,
      MMC application for 3 minutes was most effective and significant when compared
      with that of the control group (P = 0.002). Although not as significant as the
      intraoperative use of MMC (P = 0.002), old age (P = 0.026) and presence of
      diabetes mellitus (P = 0.035) were also identified as significant beneficial
      factors for decreasing the incidence of YAG capsulotomy for PCO in Cox
      proportional hazard regression analysis. CONCLUSION: Intraoperative
      subconjunctival MMC application during combined glaucoma and cataract surgery has
      a beneficial effect of inhibiting PCO after combined surgery in patients with
      POAG. Thus, after intraoperative subconjunctival application of MMC at the
      concentration of 0.5 mg/ml for 3 minutes, the aqueous MMC level must have been
      great enough to inhibit the lens epithelial cell proliferation to result in a
      long-term decrease in PCO.

PMID- 9663226
TI  - Intraocular lens changes after short- and long-term exposure to intraocular
      silicone oil. An in vivo study.
AB  - OBJECTIVE: Silicone oil frequently is used as a vitreous substitute after complex
      vitreoretinal procedures. The authors sought to study the effect of short- and
      long-term exposure to silicone oil on polymethyl methacrylate (PMMA, MC60BM;
      Alcon, Ft. Worth, TX), silicone (SI-30NB; AMO, Irvine, CA), and soft acrylic
      (MA60BM; Alcon) intraocular lenses (IOLs). DESIGN: An experimental animal study.
      INTERVENTION: Forty-one New Zealand white rabbits underwent lensectomy,
      vitrectomy, capsulotomy, and placement of one of the three types of IOLs into the
      ciliary sulcus. All lenses were weighed before implantation and 24 hours after
      explanation. In the short-term study, an fluid-air exchange was performed
      followed by the use of silicone oil (1000 centistokes) to coat the posterior lens
      surface. Immediately thereafter, an air-fluid exchange was performed and the
      remaining silicone on the posterior lens surface was aspirated or wiped or both
      for 1 minute using a soft-tipped extrusion cannula for 1 minute. In the long-term
      study, the posterior segment was filled with 1000 centistokes silicone oil after
      fluid-air exchange. Animals were observed by slit-lamp biomicroscopy and
      photographed at 1 week, 1 month, and 3 months after surgery. At 3 months, all
      animals underwent silicone-fluid exchange, an attempt to manually remove any
      remaining silicone oil, and lens explanation. RESULTS: In the short-term study,
      no silicone oil remained after manual wiping and/or aspiration in any of the four
      rabbits implanted with PMMA or acrylic IOLs. In the animals with silicone IOLs, a
      significant amount of silicone oil remained on the posterior lens surface of all
      lenses (P < 0.01 for silicone vs. acrylic and silicone vs. PMMA). No
      statistically significant difference was found when comparing the lens weights in
      each group before and after implantation. In the long-term study, aqueous droplet
      formation was found on the posterior lens surface of six of nine PMMA IOLs and
      ten of ten silicone IOLs at 3 months. No opacities were observed in the group
      with acrylic IOLs (P < 0.001 for acrylic vs. silicone, P = 0.0018 for acrylic vs.
      PMMA, and P = 0.047 for PMMA vs. silicone). Adherent silicone oil remained on two
      of nine PMMA IOLs and on none of ten acrylic IOLs. In contrast, a significant
      amount of silicone oil remained on the posterior lens surface of ten of ten
      silicone IOLs (P < 0.001 for silicone vs. acrylic and silicone vs. PMMA).
      Furthermore, there was a statistically significant increase in lens weights
      before and after implantation in the silicone IOL group but not in the PMMA or
      acrylic group (P < 0.01). CONCLUSIONS: It is extremely difficult or impossible to
      remove remaining silicone oil from the posterior surface of a silicone IOL after
      short- or long-term exposure to silicone oil. This oil may interfere with the
      surgeon's view of the retina and may diminish the patient's visual acuity. In
      contrast, oil is readily removed from the posterior surface of an acrylic IOL.
      The authors therefore recommend the use of a soft acrylic or PMMA IOL over a
      silicone IOL when choosing a lens for implantation in patients who may require
      vitreoretinal procedures with silicone oil tamponade.

PMID- 9663227
TI  - Cataract surgery combined with transpupillary silicone oil removal through
      planned posterior capsulotomy.
AB  - OBJECTIVE: The purpose of the study was to evaluate transpupillary removal of
      silicone oil combined with cataract surgery in patients after pars plana
      vitrectomy. DESIGN: A prospective case-control study. PARTICIPANTS: Fifty
      consecutive patients underwent cataract surgery combined with removal of silicone
      oil, which had served as intraocular tamponade after pars plana vitrectomy. In 28
      patients, silicone oil was removed through a planned posterior capsulotomy, and
      in 22 patients, silicone oil was removed through pars plana sclerotomies. All
      patients were operated on by the same surgeon. INTERVENTIONS: Pars plana
      vitrectomy, cataract surgery, and silicone oil removal were performed. MAIN
      OUTCOME MEASURES: Frequencies of retinal redetachment, secondary cataract,
      cystoid macular edema, and vitreous hemorrhage; visual acuity; intraocular
      pressure; and duration of surgery and visual rehabilitation were measured.
      RESULTS: Frequencies of postoperative vitreous hemorrhage (1 of 28 [4%] vs. 10 of
      22 [45%]) and secondary cataract (0 of 28 vs. 6 of 22 [27%]) were significantly
      lower (P < 0.05; chi-square test), and duration of surgery and visual
      rehabilitation were significantly shorter (P < 0.01) for patients with
      transpupillary silicone oil removal than for patients with drainage of silicone
      oil through pars plana sclerotomies. Rate of retinal redetachment (4 of 28 [14%]
      vs. 4 of 22 [18%]), time of retinal redetachment (36 +/- 32 postoperative days
      vs. 54 +/- 65 days), frequency of dislocated intraocular lenses (1 of 28 vs. 0 of
      22), and postoperative visual acuity did not vary significantly between the two
      groups. Persisting comeal endothelial decompensation and clinically significant
      cystoid macular edema due to cataract surgery were not observed in any patient.
      CONCLUSIONS: Silicone oil removal can be combined with cataract surgery. In view
      of a decreased frequency of postoperative vitreous hemorrhage, reduced rate of
      secondary cataract, and shorter duration of surgery and visual rehabilitation,
      transpupillary drainage of silicone oil through a planned posterior capsulotomy
      compares favorably with removal of silicone oil through pars plana sclerotomies.
      Retinal redetachment usually occurs within the first 3 postoperative months.

PMID- 9663228
TI  - Anterior capsule contraction and intraocular lens dislocation after implant
      surgery in eyes with retinitis pigmentosa.
AB  - OBJECTIVE: The purpose of the study was to investigate the extent of anterior
      capsule contraction, intraocular lens (IOL) decentration, and tilt after implant
      surgery in eyes with retinitis pigmentosa (RP). DESIGN: A case-control study.
      PARTICIPANTS: Forty-seven eyes from 47 patients with typical RP and 47 control
      eyes from 47 age-matched healthy patients were studied. INTERVENTION:
      Phacoemulsification surgery with polymethylmethacrylate IOL implantation with
      continuous curvilinear capsulorrhexis was performed. MAIN OUTCOME MEASURES: The
      area of the anterior capsule opening obtained with capsulorrhexis and the amount
      of the decentration and tilt of the IOL were measured using a Scheimpflug
      photography system at 1 week and 1, 3, 6, 9, and 12 months after surgery.
      RESULTS: The mean area in the RP group was found to be significantly smaller than
      that in the control group at 1 month after surgery and later (P < 0.0001). The
      percent area reduction in the RP group at 6 months was 45.2 +/- 25.8% and 4.6 +/-
      13.5% in the control group. Both the decentration length and tilt angle were also
      greater in the RP group than in the control group. Fourteen (29.8%) of the 47 RP
      eyes had undergone a neodymium:YAG (Nd:YAG) laser anterior capsulotomy at 12
      months after surgery, whereas none of the control eyes had undergone an Nd:YAG.
      CONCLUSIONS: Anterior capsule contraction in the RP eyes was more extensive than
      in the control eyes, leading to a high Nd:YAG laser anterior capsulotomy rate.
      Both lens decentration and tilt also were greater in the RP eyes than in the
      control eyes.

PMID- 9663229
TI  - A longitudinal study of body mass index and lens opacities. The Framingham
      Studies.
AB  - OBJECTIVE: The purpose of the study was to determine whether body mass index
      (BMI) is an independent risk factor for the development of nuclear, cortical, or
      posterior subcapsular lens opacities. DESIGN: A cohort study. PARTICIPANTS AND
      METHODS: Eye examinations were conducted on surviving members of the Framingham
      Heart Study Cohort from 1973 to 1975 (Framingham Eye Study I) and again from 1986
      to 1989 (Framingham Eye Study II). Data from the Framingham Heart Study,
      including weight measurements collected biennially from 1948, were used to
      examine associations between BMI (mean BMI across examinations, slope of BMI over
      time, and fluctuations in BMI) and the development of lens opacities. This
      analysis included 714 individuals, aged 52-80 years, who were free of lens
      opacities at the first eye examination. MAIN OUTCOME MEASURES: Development of
      nuclear, cortical, and posterior subcapsular lens opacities. RESULTS: A total of
      444 persons developed lens opacities during the approximately 13 years between
      eye examinations. In logistic regression analyses that controlled for age, sex,
      education, diabetes, and smoking, the risk of developing cortical opacity
      increased with higher BMI at the time of the first eye examination (P = 0.002).
      Risk of cortical opacities also increased, at a borderline level of significance,
      with higher average BMI (P = 0.09) across examinations and increasing BMI levels
      over time (P = 0.10). There was a strong association between increasing BMI over
      time and the development of posterior subcapsular lens opacities (P = 0.002). No
      associations were found for nuclear lens opacities. CONCLUSIONS: Although the
      mechanism explaining the association is unclear, these findings suggest that BMI,
      a potentially modifiable characteristic, is associated with the development of
      cortical and posterior subcapsular lens opacities.

PMID- 9663230
TI  - Retinal arteriovenous shunt at the arteriovenous crossing.
AB  - OBJECTIVE: The purpose of the study was to demonstrate that the arteriovenous
      shunt at the arteriovenous crossing could occur in major retinal vascular
      diseases other than Takayasu disease. DESIGN: Clinical review of consecutive case
      series. PARTICIPANTS: The authors studied 1885 eyes with retinal vascular
      diseases such as diabetic retinopathy, branch retinal vein occlusion, central
      retinal vein occlusion, central retinal artery occlusion, Leber's miliary
      aneurysms, Eales disease, Behcet disease, and systemic lupus erythematosus
      retinopathy. INTERVENTION: Fluorescein fundus angiography using a wide-field
      fundus camera (60 degrees) was performed. MAIN OUTCOME MEASURES: Dye transit from
      artery to vein through sequential angiography. RESULTS: The arteriovenous shunt
      at the arteriovenous crossing was found in 8 eyes with proliferative diabetic
      retinopathy, 27 eyes with branch retinal vein occlusion in the chronic stage, 2
      eyes with central retinal vein occlusion, 2 eyes with central retinal artery
      occlusion, and 2 eyes with miliary aneurysms. The arteriovenous shunt was formed
      by a direct inflow from artery to vein, showing vasodilation and
      hyperpermeability, followed by obliteration peripheral to the shunts. The pattern
      of initial inflow was classified into axial flow and laminar flow, and the inflow
      became wider and more rapid in the advanced stage. CONCLUSIONS: These findings
      indicate that the arteriovenous shunt at the arteriovenous crossing is not a
      unique phenomenon in Takayasu disease but rather is a basic pattern of retinal
      vascular reaction pathologic states.

PMID- 9663231
TI  - Discontinuation of maintenance therapy in patients with quiescent cytomegalovirus
      retinitis and elevated CD4+ counts.
AB  - OBJECTIVE: To determine whether maintenance therapy can be discontinued safety in
      patients with quiescent cytomegalovirus retinitis (CMVR) and increased CD4+
      counts after treatment with highly active antiretroviral therapy (HAART). DESIGN:
      A prospective observational case series. PARTICIPANTS: Eight human
      immunodeficiency virus (HIV)-positive patients with quiescent CMVR who were
      taking HAART and had CD4+ counts above 100 cells/microliter elected to
      discontinue anti-CMV maintenance treatment. INTERVENTION: Biweekly-to-monthly
      indirect ophthalmoscopy and fundus photographs, monthly-to-quarterly CD4+ counts,
      and quarterly HIV viral loads were ordered. MAIN OUTCOME MEASURES: Twelve
      previously affected eyes were examined for evidence of recurrent retinitis, which
      was defined as any retinal whitening, border opacification, or expansion of areas
      of retinal pigment epithelial (RPE) atrophy greater than 750 microns. Four
      previously unaffected fellow eyes were observed for new CMVR. RESULTS: There was
      no reactivation or progression of retinitis in any patient during the mean follow
      up interval of 11.4 months (range, 3-16 months). No previously unaffected eye
      developed CMVR. CD4+ remained elevated in all patients (range, 70-725; mean,
      255). The HIV viral load ranged from undetectable to 139,000 copies. CONCLUSION:
      Discontinuation of maintenance therapy may be considered in patients with HAART
      induced elevated CD4+ counts above 100 cells/microliter, prolonged relapse-free
      intervals during the reconstitution period before CD4+ counts rise above 100
      cells/microliter, and completely quiescent retinitis characterized by RPE
      scarring only. Reduced risks of drug toxicity and drug-resistant organisms are
      potential benefits. Close observation for evidence of recurrent retinitis is
      indicated.

PMID- 9663232
TI  - Uveal lymphoid infiltration. Report of four cases and clinicopathologic review.
AB  - PURPOSE: The purpose of the study was to report the clinicopathologic features of
      four patients with uveal lymphoid infiltration who were diagnosed by a
      conjunctival biopsy. DESIGN: A case series. PARTICIPANTS: Four patients at four
      institutions participated. MEASURES: The histopathologic findings of the
      conjunctival and episcleral biopsy specimens from four patients with the
      diagnosis of uveal lymphoid infiltration were recorded. The conjunctival
      specimens were placed in 10% neutral buffered formaldehyde solution or B5
      solution and processed routinely for light microscopic examination and
      immunohistochemical analysis for B cells and T cells and kappa and lambda light
      chains. The clinical and histopathologic findings were compared with 47
      previously reported cases of uveal lymphoid infiltration. RESULTS: Two men and
      two women (average age = 57 years) presented with diffuse punctate to coalescent
      yellow uveal infiltrates and epibulbar pink fleshy lesions. Ultrasonography of
      the lesions showed diffuse choroidal thickening and a lack of choroidal or
      scleral excavation. The conjunctival biopsy specimens showed diffuse infiltration
      of the substantia propria with B lymphocytes with variable kappa and lambda
      restriction. Scattered T lymphocytes also were present. Plasmacytoid cells and a
      prominent Grenz zone were present. CONCLUSIONS: Patients with solitary or
      multiple yellow uveal infiltrates should have careful conjunctival evaluation for
      the presence of pink conjunctival lesions. Biopsy specimens of the conjunctival
      lesion may establish the diagnosis of uveal lymphoid infiltration.

PMID- 9663233
TI  - Alstrom syndrome. Report of 22 cases and literature review.
AB  - OBJECTIVE: The authors report 22 cases of Alstrom syndrome (AS), which is the
      largest series to date. Only 37 cases have been reported in the world literature
      since 1959. The authors review the clinical features and compare these with the
      overlapping condition of Bardet-Biedl syndrome. Their aim is to clarify the AS
      phenotype and to increase awareness of the early features. DESIGN: A
      retrospective case series. PARTICIPANTS: All patients (22) with a diagnosis of AS
      admitted to the authors' hospital in the past 10 years were included in this
      review. INTERVENTION: This is principally a review of ocular features, but other
      features are recorded and discussed. MAIN OUTCOME MEASURES: Features noted
      included age at onset of visual symptoms, presence of photophobia, visual acuity,
      and electroretinogram findings. Nonocular features recorded included cardiac
      status, weight and height, hearing, and presence of diabetes mellitus. RESULTS:
      Cardiomyopathy presenting in infancy has only been recognized recently to be a
      feature of AS. Of the authors' cases, 18 of 22 had infantile cardiomyopathy. In
      the authors' tertiary referral institution, there is an ascertainment bias toward
      younger patients and especially those with pathology that is other than ocular
      pathology. In addition, AS is difficult to recognize in childhood without the
      development of infantile cardiomyopathy. Alstrom syndrome often is not recognized
      until diabetes mellitus develops in the second or third decade. Initially, a
      diagnosis of cone-rod dystrophy, achromatopsia, Leber's congenital amaurosis, or
      Bardet-Biedl syndrome may be made. In AS, there is a severe infantile retinal
      dystrophy. The electroretinogram is absent or attenuated with better preserved
      rod than cone function. The retinal dystrophy is progressive with the patient's
      visual acuity of 6/60 or less by 10 years of age and no light perception by 20
      years of age. CONCLUSIONS: A diagnosis of AS should be considered in infantile
      cone and rod retinal dystrophy, particularly if the weight is above the 90th
      percentile (16 of 18 cases) or if there is an infantile cardiomyopathy (18 of 22
      cases).

PMID- 9663234
TI  - Fisher syndrome associated with IgG anti-GQ1b antibody following infection by a
      specific serotype of Campylobacter jejuni.
AB  - OBJECTIVE: The purpose of the study was to describe clinical and serologic
      features of Fisher syndrome associated with IgG anti-GQ1b ganglioside antibody
      following Campylobacter jejuni enteritis. DESIGN: A clinical trial. PARTICIPANTS:
      Four consecutive patients with Fisher syndrome were studied. INTERVENTION:
      Samples of sera from four patients were tested for reactivity to GQ1b ganglioside
      by enzyme-linked immunosorbent assay (ELISA). Campylobacter jejuni strains
      isolated from samples of stool from three patients were serotyped by the method
      of Penner and Hennessy and that of Lior. MAIN OUTCOME MEASURES: Serum IgG anti
      GQ1b antibody titer and serotypes of C. jejuni. RESULTS: Diplopia occurred 8 to
      14 days after the onset of diarrhea. Campylobacter jejuni was isolated from
      samples of stool from all of the patients. ELISA revealed a high serum IgG anti
      GQ1b antibody titer for all four patients. Two patients had high serum titers of
      other antiganglioside antibodies frequently related to Guillain-Barre syndrome.
      These two patients developed limb weakness following the onset of
      ophthalmoplegia. The C. jejuni serotype was Penner's serotype 2 for all three of
      the patients tested. CONCLUSIONS: These findings suggest that C. jejuni,
      especially Penner's serotype 2, enteritis could trigger development of Fisher
      syndrome associated with IgG anti-GQ1b antibody.

PMID- 9663235
TI  - Chronic keratoconjunctivitis associated with congenital dyskeratosis and
      erythrokeratodermia variablis. Two rare genodermatoses.
AB  - OBJECTIVE: The purpose of the study was to report the ocular manifestations and
      immunohistopathologic description of two rare forms of genodermatosis: congenital
      dyskeratosis (CD) and erythrokeratodermia variabilis (EKV). DESIGN: Case reports.
      PARTICIPANTS: Two patients with CD and EKV presenting with chronic
      keratoconjunctivitis were studied. INTERVENTION: Clinical photography to show
      ocular manifestations and dermatologic findings was performed. Conjunctival
      biopsy was performed to determine the histopathology and immunohistopathology.
      RESULTS: In the patient with EKV, the eyelid skin was dry, erythematous, and
      thickened. The lid margins showed plugging of some of the Meibomian glands,
      madarosis, and occasional trichiasis. The epibulbar conjunctiva was injected and
      had a moderate papillary reaction. Both corneas had pronounced vascularization
      and stromal scarring. Conjunctival biopsy results disclosed a striking number of
      degranulating mast cells and moderate numbers of plasma cells.
      Immunohistopathology showed pronounced immunoglobulin G (IgG)-positive cells in
      the stroma and immunoglobulin A (IgA) positivity in the epithelium. There was
      scattered immunoglobulin M (IgM) and moderate C3 and C4 positivity in the stroma.
      In CD, the patient had keratinized lid margins, entropion formation, trichiasis,
      cicatrizing conjunctivitis, and symblephra formation. The corneal surface was
      keratinized, with deep and superficial vascularization. Conjunctival biopsy
      specimens showed pronounced epithelial keratinization and squamous metaplasia.
      Degranulating mast cells and eosinophils were prominent in the stroma.
      Immunohistopathology showed C4 and immunoglobulin D positivity on the keratinized
      epithelial surface with rare foci of immunoglobulin E-positive cells. Basal
      epithelial cells were positive for IgA and IgG, and a large number of IgA and IgG
      plasma cells were present in the substantia propria. CONCLUSION: To the authors'
      knowledge, these case reports represent the first clinical description of the
      ocular manifestation of EKV and the first immunohistopathologic description of
      the affected conjunctiva in EKV and CD, both of which should be considered in the
      differential diagnosis of genodermatosis associated with chronic
      keratoconjunctivitis.

PMID- 9663236
TI  - Prevalence of myopia between 3 months and 5 1/2 years in preterm infants with and
      without retinopathy of prematurity. Cryotherapy for Retinopathy of Prematurity
      Cooperative Group.
AB  - PURPOSE: The purpose of the study was to examine spherical equivalent refractive
      errors, especially myopia, at six ages between 3 months and 5 1/2 years post-term
      in preterm children with birth weights of less than 1251 g. DESIGN: A cohort
      study. PARTICIPANTS: There were a total of 827 participants in the multicenter
      study of cryotherapy for retinopathy of prematurity (ROP). Approximately one
      third of the eyes did not develop ROP, whereas two thirds developed mild-to
      severe ROP. None of the eyes underwent cryotherapy. INTERVENTION: Refractive
      error was measured at 3 months, 1 year, and 5 1/2 years term due date at the five
      long-term follow-up centers. In most eyes, refractive error also was measured at
      2, 3 1/2, and 4 1/2 years. MAIN OUTCOME MEASURE: Myopia was defined as 0.25
      diopter (D) or greater with high myopia as 5 D or greater. RESULTS: The
      proportion of eyes with myopia in this preterm population was increased compared
      to published data on full-term children and was related to severity of both acute
      phase and cicatricial-phase ROP. The percentage of eyes with myopia varied little
      across ages, ranging from 21.2% at 1 year to 15.7% at 4 1/2 years. The percentage
      of eyes with high myopia doubled from 1.8% to 3.9% between 3 months and 1 year
      and remained stable thereafter. The distribution of refractive errors in eyes
      with mild acute-phase ROP was similar to that of eyes with no ROP. In contrast,
      eyes with moderate or severe acute-phase ROP showed an increased prevalence of
      high myopia. The distribution of refractive errors changed between 3 months and 1
      year with little change after 1 year. This pattern of refractive development
      differs from that of full-term infants. Birth weight, severity of ROP, and degree
      of myopia at 3 months predicted the presence of myopia and high myopia at 5 1/2
      years of age. CONCLUSIONS: The distribution of refractive errors in preterm
      infants from age 3 months to 5 1/2 years varies with severity of acute-phase ROP
      and cicatricial disease. Changes in refractive error distribution occur primarily
      between 3 months and 1 year and involve a decrease in the proportion of eyes with
      hyperopia and an increase in the proportion with high degrees of myopia.

PMID- 9663237
TI  - The accuracy of experienced strabismologists using the Hirschberg and Krimsky
      tests.
AB  - OBJECTIVE: The purpose of the study was to assess the accuracy of a group of
      strabismologists applying the Hirschberg and Krimsky tests. DESIGN: A clinical
      trial. PARTICIPANTS: Sixteen very experienced strabismologists participated in
      this study. INTERVENTION: The participants were asked to evaluate slides of four
      different patients using the Hirschberg method and to evaluate two of the four
      patients with the Krimsky method. The slides included a patient with 25 delta
      left esotropia, a patient with 25 delta right exotropia, a patient with 80 delta
      esotropia with a positive angle kappa, and a patient with 75 delta infantile
      esotropia. Alternate prism and cover testing was performed immediately after the
      photograph was taken and considered to be the actual deviation of the patient.
      MAIN OUTCOME MEASURE: Measured was the accuracy in assessing the angle of
      strabismus. RESULTS: With the Hirschberg method, each participant underestimated
      at least one patient by at least 10 delta. In addition, the participants tended
      to underestimate both large and small angle esotropic and exotropic patients with
      greater errors of estimation occurring with larger angles of strabismus. With the
      Krimsky method, a majority of participants overestimated at least one patient by
      10 delta and showed difficulty in appreciating differences of 5 delta. In
      addition, the authors noted inconsistent responses by each participant.
      CONCLUSION: The Hirschberg and Krimsky methods are substantially less accurate
      than the alternate prism and cover test.

PMID- 9663238
TI  - Success rates of nasolacrimal duct probing at time intervals after 1 year of age.
AB  - OBJECTIVE: The purpose of the study was to determine the success rate of probing
      for congenital nasolacrimal duct obstruction after 1 year of age. DESIGN: A
      record review. PARTICIPANTS AND INTERVENTION: Two hundred fifty-two patients with
      303 obstructed nasolacrimal ducts underwent probing and irrigation by the author
      between 1971 and 1997 while under brief general anesthesia. MAIN OUTCOME
      MEASURES: Successful outcome of probing was defined as absence of tearing and
      discharge in the affected eye. RESULTS: The overall cure rate in all patients was
      92%, varying from 88.9% to 96.8% at different age intervals up to and beyond 3
      years of age. Chi-square analysis showed no significant change in cure rate with
      increasing age. CONCLUSION: Probing for congenital nasolacrimal duct obstruction
      beyond 1 year of age is highly successful, and the cure rate does not vary
      significantly at intervals of increasing age.

PMID- 9663239
TI  - Porous polyethylene orbital implant in patients with retinoblastoma.
AB  - OBJECTIVE: The purpose of the study was to assess integration of porous
      polyethylene allografts in 37 anophthalmic sockets of retinoblastoma
      enucleations. DESIGN: A clinical review. PARTICIPANTS: Thirty-four patients (19
      female, 15 male) whose age when diagnosed with retinoblastoma ranged from 1 to 72
      months participated. Sixteen patients had unilateral retinoblastoma and 18 had
      bilateral retinoblastoma. INTERVENTION: Enucleation (3 bilateral, 31 unilateral)
      with implantation of a porous polyethylene (PP) sphere (16-20 mm in diameter) was
      performed. Of the 37 spheres, 34 were primary implants and 3 were secondary
      implants. In the eight patients with postimplantation exposure, the PP implant
      had to be removed. MAIN OUTCOME MEASURES: Data on eight sockets with exposed PP
      implant were measured. RESULTS: There were no implant extrusions, but
      conjunctival dehiscence-exposure occurred in eight patients (21.6%). In 3 of 37
      sockets, the volume replacement was not good, and in 5 cases, fornices were too
      shallow to accommodate a well-fitting prosthesis. In all but one socket, the
      overall cosmesis was graded subjectively from acceptable (grade 2) to excellent
      (grade 3). CONCLUSIONS: Although the PP implant is a useful and a less-expensive
      alternative to hydroxyapatite in the porous matrix implant category, if
      conjunctival exposure takes place, the implant presents a serious management
      problem because of its nonresponsiveness to medical and surgical treatments.

PMID- 9663240
TI  - Primary iris stromal cysts. A report of 17 cases.
AB  - OBJECTIVE: To describe clinical characteristics, management, and complications of
      primary iris stromal cysts. DESIGN: A retrospective review. RESULTS: Seventeen
      consecutive patients with primary iris stromal cysts were found. Nine (52%)
      patients were diagnosed under age 10 years (range, 1 day-7 years), and eight
      (47%) patients were diagnosed after age 10 years (range, 14-71 years). Overall,
      the cyst appeared unilaterally as a solitary clear translucent mass dissecting
      the iris stroma in all cases. The children with a primary iris stromal cyst
      demonstrated a more aggressive course than teenagers or adults. In children, the
      cyst obstructed the visual axis in eight cases (88%), requiring treatment such as
      aspiration, cryotherapy, and resection. In seven children, multiple treatments
      were necessary. Ultimate control of the cyst was achieved in all cases using
      techniques of needle aspiration (with or without cryotherapy) in three cases and
      using resection in five cases. Primary iris stromal cysts in teenagers and adults
      necessitated intervention in only two cases (25%). CONCLUSION: Primary iris
      stromal cysts can occur in children, teenagers, and adults. In children, primary
      stromal iris cysts appear to have a more aggressive clinical course, often
      requiring several treatments for globe and vision preservation.

PMID- 9663241
TI  - Detection of varicella zoster virus DNA and viral antigen in human eyes after
      herpes zoster ophthalmicus.
AB  - OBJECTIVE: The purpose of the study was to identify varicella zoster virus (VZV)
      DNA and viral antigen in human eyes at various intervals after clinical onset of
      herpes zoster ophthalmicus (HZO). DESIGN: A retrospective case series.
      PARTICIPANTS: There were 9 eyes and 4 corneal buttons surgically obtained from 13
      patients with HZO at the University Eye Hospital of Erlangen-Nurnberg between
      1984 and 1994. Specimens were examined at different timepoints after clinical
      onset of HZO (range, 1 day-19 years; median, 36 months). METHODS: Histopathologic
      evaluation was performed on formalin-fixed and paraffin-embedded tissue by
      routine histology, immunohistochemistry (5-B-7 murine monoclonal antibody to VZV;
      peroxidase-antiperoxidase method), and DNA-in situ hybridization (35S
      deoxyadenosine triphosphate-labeled HindIII fragments [A and C] of VZV). RESULTS:
      Typical histopathologic changes associated with HZO were identified:
      vascularization of the corneal stroma (11 of 13), granulomatous reaction to
      Descemet's membrane (8 of 13), fusiform-shaped ciliary scarring (5 of 9), optic
      neuritis (4 of 9), and perineuritis (8 of 9) and perivasculitis (8 of 9) of the
      long posterior ciliary nerves and arteries. VZV antigen was detected in two
      patients with acute infection 1 and 7 days after onset of HZO, respectively. VZV
      DNA was identified in seven patients up to 10 years after onset of HZO in corneal
      epithelial cells (2 of 13), corneal stroma (5 of 13), inflammatory infiltrate of
      the anterior chamber (1 of 9), episclera (2 of 9), posterior ciliary nerves (1 of
      9) and arteries (5 of 9), optic nerve (5 of 9), and adjacent leptomeninges (2 of
      9). CONCLUSION: Persistence of viral genomes, most likely accompanied by gene
      expression or slow viral replication, appears to be responsible for the often
      smoldering panophthalmitis and the chronic recurrent keratouveitis in patients
      with HZO. Localization of viral DNA in vascular structures suggests a role for
      vasculitis in the pathogenesis of some ocular findings associated with HZO.

PMID- 9663242
TI  - Ectopia lentis et pupillae. A hypothesis revisited.
AB  - BACKGROUND: Ectopia lentis et pupillae (ELeP) is a rare congenital inherited
      disorder characterized by lenticular and pupillary ectopia. Recent speculation on
      its pathogenesis is based on clinical observation and includes a neuroectodermal
      defect or persistence of fetal vasculature. None of these reports included
      histopathology or imaging studies. STUDY DESIGN: Case report and literature
      review. INTERVENTION: The authors examined a 55-year-old woman with ELeP using 10
      MHz and 50-MHz ultrasonography to demonstrate the structural abnormalities
      present. Five patients (eight eyes) who had undergone cataract extraction without
      lens implantation were also examined. RESULTS: In the patient with ELeP, the
      right pupil was displaced inferiorly and the left temporally. An ultrasound scan
      at 10 MHz showed both lenses lying inferiorly in the vitreous. An ultrasound scan
      at 50 MHz allowed detailed examination of the anterior segment, including the
      iris and ciliary body, and showed two main features in each eye, including a lack
      of definition of ciliary processes, except in that quadrant toward which the
      pupil was displaced, and a membrane-like structure extending forward and
      attaching to the proximal pupil margin. The membrane passed over the tips of the
      ciliary processes to a more posterior origin. CONCLUSIONS: The only histologic
      reports of this condition are from the beginning of this century in the German
      literature. Ultrasonography at 50 MHz allows high-resolution in vivo imaging of
      anterior structures that are not clinically visible. The authors' findings in
      this case of ELeP are sufficiently different from those of non-ELeP-related
      aphakia to suggest that they are not solely due to aphakia. Furthermore, the
      authors' findings are very similar to the only histologic reports suggesting that
      the pupillary and lenticular ectopia results from mechanical tethering of the
      pupil with zonular disruption. This hypothesis has not been discussed in the
      recent literature.

PMID- 9663243
TI  - A bedside test to determine motion stereopsis using the Pulfrich phenomenon.
AB  - OBJECTIVE: Many diseases induce asymmetric delays in the visual pathway,
      resulting in a spontaneous Pulfrich phenomenon (PP). The PP is a visual
      stereoillusion that may cause difficulties in persons when traveling in cars,
      crossing the road, or playing ball games. The authors developed and tested a
      simple new bedside procedure to detect PP. DESIGN: A case series. PARTICIPANTS:
      Disease simulation in 2 normal subjects and 18 patients with optic neuritis (ON)
      was examined. Ninety normal subjects were studied to determine normal range of
      PP. INTERVENTION: The new test, called swinging pen test (SPT), is performed by
      oscillating a pen by hand. The SPT was compared to a gold standard, a mechanical
      pendulum (MP). MAIN OUTCOME MEASURES: The authors measured simulated PP in two
      normal subjects and PP in 18 patients with ON and 90 normal control subjects. The
      Pearson product-moment correlation (r) and the Spearman rank correlation (rs)
      between SPT and MP were calculated. RESULTS: The magnitudes of simulated PP
      determined with the SPT and the MP correlated well (r = 0.92, P < 0.005, and r =
      0.96, P < 0.001). Correlation also was good in patients with ON (rs = 0.90, P <
      0.05). The positive predictive value of the SPT was 100%, and the negative
      predictive value was 92%. The PP was absent in all control subjects testing with
      either pendulum. The normal range for PP varied from -1.40 to 1.52 msec. For the
      SPT, the intraobserver variability coefficient was 8.2%, and the interobserver
      variability coefficient was 10.5%. CONCLUSIONS: The authors believe that SPT will
      be of value to clinicians on bedside evaluation of motion stereopsis
      dysfunctions. The normal range of PP was approximately +/- -1.5 msec
      (approximately +/- -1.5 cm), corresponding to a 0.3-log unit neutral density
      filter).

PMID- 9663244
TI  - Autotransplantation of parathyroid glands into subcutaneous forearm tissue for
      renal hyperparathyroidism.
AB  - BACKGROUND: Autotransplantation of diseased parathyroid glands into subcutaneous
      adipose tissue has been mentioned previously, but as far as we know there is no
      previous systemic study concerning parathyroid function after subcutaneous
      autotransplantation. METHODS: From January 1993 to June 1996, total
      parathyroidectomy and autotransplantation were carried out in 46 patients with
      renal hyperparathyroidism. The symptoms and signs before operation were
      intractable pruritus in 29 patients (63%), bone pain in 27 patients (58.7%),
      general weakness in 17 patients (37%), soft tissue calcification in 15 patients
      (32.6%), bone fracture in one patient, and failure to thrive in one patient.
      Twenty-four patients (group A) underwent autotransplantation of 60 mg of a
      diffuse hyperplastic parathyroid gland into subcutaneous forearm tissue, and 22
      patients (group B) underwent autotransplantation of 15 pieces (60 mg) of 1 mm3
      tissue into forearm muscles, as mentioned previously. Four patients in group A
      and one in group B who had high levels of intact parathyroid hormone (I-PTH)
      immediately after operation were excluded. After the operation, calcium
      carbonate, 1.5 to 16 gm daily, and calcitriol, 0.25 to 1.5 micrograms/daily, were
      prescribed according to the patients' calcium levels. RESULTS: After 6 months,
      all patients in both groups were given calcium carbonate, 1 gm/day, and
      calcitriol, 0.25 microgram/day, for parathyroid suppression, and none had to take
      more medicine to maintain calcium levels. There were no significant differences
      between the two groups regarding serum calcium, phosphorous, alkaline
      phosphatase, and I-PTH levels 1 week, 3 to 6 months, and 1 year after operation.
      Eighteen patients in group A and 19 patients in group B had normal levels of I
      PTH 1 year after operation. In the follow-up period from 1 to 3 1/2 years, only
      one patient in group A had a subnormal I-PTH level and one in group B had graft
      dependent hyperparathyroidism. CONCLUSIONS: We therefore suggest that
      autotransplantation of a parathyroid gland into forearm subcutaneous tissue for
      renal hyperparathyroidism is as effective as autotransplantation into forearm
      muscles and can be done easier.

PMID- 9663245
TI  - Diagnosis of asymptomatic common bile duct stones: preoperative endoscopic
      ultrasonography versus intraoperative cholangiography--a multicenter, prospective
      controlled study. French Associations for Surgical Research.
AB  - BACKGROUND: In patients with symptomatic cholelithiasis, preoperative diagnosis
      of common bile duct (CBD) stones can modify the therapeutic strategy. The aims of
      this prospective, controlled multicenter study were to assess the feasibility,
      concordance, discordance, and indexes such as sensitivity, specificity, positive
      and negative predictive values, and accuracy of preoperative endoscopic
      ultrasonography compared with those of intraoperative cholangiography (IOC) in
      the diagnosis of asymptomatic CBD stones (i.e., patients undergoing
      cholecystectomy with no clinical or biologic evidence of CBD stones). METHODS:
      From October 1993 to October 1995, 240 consecutive patients with symptomatic
      cholelithiasis, scheduled for cholecystectomy in 14 surgical centers, were
      enrolled in this study. All patients were selected for this study according to a
      preoperative high-risk CBD stone predictive score. Each patient underwent both
      endoscopic ultrasonography and IOC, as well as surgical exploration of the CBD
      when stones were detected during one or both preoperative investigations. All
      patients were seen 1 months and 1 year after operation to check for residual
      stones. RESULTS: The feasibility of endoscopic ultrasonography was significantly
      higher overall than that of IOC (99% vs 90%; p < 0.001), except when IOC was
      through a laparotomy (97% vs 93%; p = 0.16). The number of patients available for
      study was 215. In 198 cases (92%), results of both investigations were in
      concordance (161 negative and 37 positive values). Seventeen cases (8%) were
      discordant. There was overall concordance between the two investigations (kappa
      coefficient 0.764; 95% confidence interval 0.66 to 0.87), but the percentage of
      discordance was in favor of IOC. Sensitivity and specificity of IOC were
      significantly higher than those of endoscopic ultrasonography (1.00 and 0.98 vs
      0.85 and 0.93, respectively). With a prevalence of CBD stones of 19%, positive
      and negative predictive values of IOC were significantly higher than those of
      endoscopic ultrasonography (0.93 and 1.00 vs 0.75 and 0.96, respectively).
      CONCLUSIONS: Although endoscopic ultrasonography is feasible more often than IOC,
      IOC is associated with a slightly lower degree of discordance and better
      information indexes and remains an efficient method of investigation for CBD
      stones. Endoscopic ultrasonography can be suggested in preference to endoscopic
      retrograde cholangiography when postoperative residual stones are suspected but
      need not be performed routinely before cholecystectomy.

PMID- 9663246
TI  - Acute biliary pancreatitis: the roles of endoscopic ultrasonography and
      endoscopic retrograde cholangiopancreatography.
AB  - BACKGROUND: Acute biliary pancreatitis, particularly severe pancreatitis,
      necessitates urgent diagnosis and treatment of common bile duct (CBD) stones. The
      roles of urgent endoscopic ultrasonography (EUS) and endoscopic retrograde
      cholangiopancreatography (ERCP) in the management of biliary pancreatitis were
      prospectively studied. METHODS: Thirty-five consecutive patients with suspected
      acute biliary pancreatitis underwent urgent ultrasonography, computed tomography
      (CT), EUS, and ERCP. Endoscopic sphincterotomy (ES) was performed for CBD stones.
      We investigated (1) imaging diagnostic results of CBD stones and intrapancreatic
      and extrapancreatic pathology and (2) the outcome of ERCP. RESULTS: Imaging
      studies established a biliary origin in 24 patients, 15 with and 9 without CBD
      stones. According to Acute Physiology and Chronic Health Evaluation II scores, 6
      had severe and 18 had mild pancreatitis. EUS (100%) and ERCP (100%) were
      significantly more sensitive for CBD stones than were ultrasonography (47%) and
      CT (47%). EUS detected pancreatic necrosis (100%), as well as inflammation in the
      lesser sac (100%) and retroperitoneum (81%), which CT confirmed. No complications
      related to ERCP occurred. After ES, rates of morbidity and mortality related to
      pancreatitis were 8% and 0%, respectively. CONCLUSIONS: EUS, an accurate and
      minimally invasive modality, may limit ERCP to therapeutic use in biliary
      pancreatitis. EUS is recommended if ultrasonography and CT have failed to detect
      CBD stones. CBD stones should be treated with urgent ES.

PMID- 9663247
TI  - Surgery on trial: an account of clinical trials evaluating operations.
AB  - BACKGROUND: The objective of this study was to review published clinical trials
      to determine the level of compliance with issues relevant to operations. METHODS:
      We evaluated 10 methodologic criteria in 186 trials that were published in 10
      prestigious journals between January 1986 and December 1995. RESULTS: One quarter
      of the trials failed to provide a clear account of the operative technique, 34%
      of the trials did not adequately detail the adverse events that occurred after
      operation, and 40% of the trials neglected to declare the nature and success of
      the follow-up of patients after the operation. Only 35% of the trials indicated
      that there was an attempt to standardize either the surgical procedure or
      perioperative care. In addition, less than 20% of the trials declared a method
      for assessing compliance with the surgical protocol or commented on the use of
      resources during the perioperative period. CONCLUSIONS: Greater attention needs
      to be paid to the specific issues that arise when operations are evaluated in
      clinical trials.

PMID- 9663248
TI  - Outcomes of atypical symptoms attributed to gastroesophageal reflux treated by
      laparoscopic fundoplication.
AB  - BACKGROUND: The introduction of laparoscopic fundoplication (LF) has lowered the
      threshold for operation in patients with symptoms attributed to gastroesophageal
      reflux. We sought to determine whether the outcomes in patients referred for
      atypical symptoms (pulmonary, pharyngolaryngeal, and pain syndromes) were as good
      as those referred for correction of heartburn and regurgitation (typical
      symptoms). METHODS: Thirty-five of 150 consecutive patients undergoing LF with a
      minimum of 12 months of follow-up were referred primarily for correction of
      atypical symptoms. A standard preoperative evaluation included endoscopy,
      manometry, upper gastrointestinal contrast radiography, and 24-hour pH probe
      testing (33 of 35 patients with atypical symptoms). Patients completed a symptom
      questionnaire administered by a study nurse before the operation and 3 and 12
      months after the operation. Symptoms were scored from 0 to 10. RESULTS: Heartburn
      was relieved by LF in 93% of patients, whereas only 56% of patients had relief of
      atypical symptoms. Furthermore, the degree of improvement in typical symptoms was
      greater than that seen for atypical symptoms as measured by the 0 to 10-symptom
      rating score (improvement in typical symptoms = 6.2 vs improvement in atypical
      symptoms = 4.4 [p = 0.01]). The response rate for laryngeal, pulmonary, and
      epigastric/chest pain symptoms was 78%, 58%, and 48%, respectively. Analysis of
      factors associated with relief of atypical symptoms revealed that response to a
      preoperative trial of omeprazole or H2-blockers was significantly associated with
      successful surgical outcome (p = 0.03). Six of seven patients with laryngeal
      symptoms who had acid reflux above the cricopharyngeal level shown by dual-probe
      pH testing had relief of the symptoms after LF. Manometric findings (amplitude of
      esophageal body contractions, propagation of contractions, and lower esophageal
      sphincter resting pressure) neither predicted nor correlated with relief of
      atypical symptoms after the operation. CONCLUSIONS: Relief of atypical symptoms
      attributed to gastroesophageal reflux by LF is less satisfactory and more
      difficult to predict than relief of heartburn and regurgitation. The only useful
      preoperative predictors of relief of atypical symptoms in this study were the
      response to pharmacologic acid suppression and dual-probe pH testing (only in
      patients with laryngeal symptoms).

PMID- 9663249
TI  - Delayed hepatic resection for ruptured hepatocellular carcinoma.
AB  - BACKGROUND: Although transcatheter arterial embolization is advocated as initial
      therapy for ruptured hepatocellular carcinoma (HCC), hepatic resection is
      necessary for cure. The effectiveness of delayed hepatic resection for ruptured
      HCC was determined. METHODS: The records of 10 patients who underwent delayed
      hepatic resection for ruptured HCC were reviewed. RESULTS: All patients were men,
      and the mean age was 63 years. For hemostasis, transcatheter arterial
      embolization was performed in three patients, whereas in the other patients
      bleeding stopped without special procedures. Mean interval from rupture to
      hepatic resection was 74 days. Liver function test results before hepatic
      resection were almost normal. Trisegmentectomy in one and bisegmentectomy in four
      patients were performed, whereas minor hepatic resection was performed for four
      extrahepatic HCCs. There were no operative or hospital deaths. Four patients had
      cirrhosis. The mean tumor diameter was 7.5 cm. Of seven patients with recurrence,
      two with dissemination had tumors that ruptured on the inferior aspect of the
      liver. The 1- and 3-year survival rates were 77% and 48%, respectively.
      CONCLUSIONS: Because delayed hepatic resection for ruptured HCC was safe and
      compared similarly with that for other patients who underwent resection for HCC,
      it should be used. However, when HCC ruptures in an inferior location, recurrence
      of tumor as dissemination is likely.

PMID- 9663250
TI  - Mucosal melanoma of the female genitalia: a clinicopathologic study of forty
      three cases at Duke University Medical Center.
AB  - BACKGROUND: Mucosal melanoma of the female genitalia is a rare neoplasm. Only
      nine reports reviewing more than 40 patients have been published on this subject
      in the past 30 years. These lesions arise from melanocytes, which can be found
      within the mucosa lining the female genital tract. Surgical resection is the
      mainstay of therapy, with little use for other modalities except in palliative
      roles. The overall prognosis is poor, with reported 5-year survival rates usually
      below 50%. METHODS: Forty-three patients with primary mucosal melanoma of the
      female genitalia seen at the Duke University Medical Center Melanoma Clinic
      during a 25-year period were studied retrospectively. Specific information was
      obtained from the patients' clinic charts and computerized databases. RESULTS:
      Thirty vulvar, nine vaginal, and four cervical lesions were identified. The
      median age at diagnosis was 61.4 years. At initial presentation, two thirds of
      the patients had localized disease only. Tumor ulceration and thickness of the
      primary lesion had a measurable impact on prognosis, whereas the presence of
      regional metastases at presentation did not. All but one patient underwent
      resection with curative intent. The performance of radical operations did not
      improve outcome among patients with vulvar melanoma. Many of the treatment
      failures were the result of local recurrences, hinting at the need to improve
      local control. Despite therapy, the overall corrected 5-year survival rate was
      54%. CONCLUSIONS: Prospective multicenter trials for patients with vulvovaginal
      melanoma could be helpful in establishing uniform, standardized surgical
      protocols and delineating the applicability of new modalities and therapies, such
      as lymphoscintigraphy with sentinel node biopsy and high-dose interferon.

PMID- 9663251
TI  - Effect of intermittent hepatic pedicle clamping on free radical generation in the
      rat liver.
AB  - BACKGROUND: Intermittent hepatic pedicle clamping is thought to cause less
      hepatic reperfusion injury compared with continuous clamping. The mechanisms
      underlying this difference are unknown. We examined the relationship between
      intermittent ischemia/reperfusion and the production of free radicals using
      electron spin resonance spectrometry. METHODS: Alpha-(4-pyridyl 1-oxide)-N-tert
      butylnitrone was administered to rats as a spin trap agent. Continuous clamping
      (15, 30, or 60 minutes) or intermittent clamping (four cycles of 15-minute
      ischemia and 5 or 15 minutes of reperfusion) of hepatic pedicle was carried out.
      After reperfusion, free radical production in the liver was measured by an
      electron spin resonance spectrometer, and the level of hepatic injury was
      evaluated by measuring liver enzyme. RESULTS: Longer periods of ischemia
      increased free radical production after reperfusion. There was no significant
      increase in free radical production or liver enzymes when the duration of
      ischemia was 15 minutes. Free radical production and liver damage were
      significantly less severe in intermittent pedicle clamping than in continuous
      clamping for 60 minutes, especially when the duration of the reperfusion between
      four cycles of ischemia was 15 minutes. CONCLUSIONS: These results indicate that
      intermittent pedicle clamping lessens free radical production when compared with
      continuous clamping, although many free radicals are produced.

PMID- 9663252
TI  - Partial hepatectomy accelerates local tumor growth: potential roles of local
      cytokine activation.
AB  - BACKGROUND: Surgical excision of liver tumors represents the only curative
      treatment for primary and metastatic liver malignancies. It has been suspected
      that hepatectomy may stimulate growth of microscopic tumors. To determine whether
      local or systemic factors after hepatectomy are responsible for enhancement of
      tumor growth, the effects of hepatectomy on the experimental growth of liver or
      pulmonary tumors were examined. METHODS: One hour after injection of 10(6) Morris
      hepatoma cells into either the portal or femoral vein, which produces isolated
      liver and lung tumors, respectively, animals were randomized to undergo 0%, 30%,
      or 70% partial hepatectomy (PH). RESULTS: Animals that underwent portal injection
      of tumor had significantly increased liver tumor burden after PH (sham, 25 +/- 7
      vs PH, 94 +/- 17; p < 0.01), whereas animals that underwent femoral injection had
      no change in lung tumor burden after PH. PH was associated with significantly
      increased levels of transforming growth factor-alpha, transforming growth factor
      beta, and basic fibroblast growth factor in the liver but not in the lung.
      CONCLUSIONS: Changes in liver cytokine-growth factor activation may contribute to
      enhanced tumor growth in the liver after hepatectomy.

PMID- 9663253
TI  - Plasma levels of high-energy compounds compared with severity of illness in
      critically ill patients in the intensive care unit.
AB  - BACKGROUND: Plasma metabolic changes have been shown to reflect deterioration of
      the energy state of tissue in studies in animals. This study evaluates whether
      high-energy compounds and their metabolites in plasma reflect the clinical
      condition and predict outcome in critically ill patients. METHODS: Thirteen
      critically ill patients with major trauma, severe septic shock, or cardiogenic
      shock (initial Acute Physiology and Chronic Health Evaluation [APACHE] II score >
      or = 16) were studied. The APACHE II score was recorded daily until discharge
      from the intensive care unit or death. The plasma contents of adenosine
      triphosphate, adenosine diphosphate, adenosine, inosine, hypoxanthine, creatine
      phosphate, creatine, uric acid, and lactic acid were determined daily. Fifteen
      healthy volunteers were used as control subjects. RESULTS: All patients with an
      APACHE II score of 12 or less at some time during their stay in the intensive
      care unit survived (n = 4); all patients with a score of 26 or higher died (n =
      5). The initial APACHE II median score for survivors was 21 (range 16 to 25; n =
      7) and for nonsurvivors 24 (range 17 to 28; n = 6) (difference not significant).
      The final APACHE II score for the survivors was 11 (range 3 to 16) and for
      nonsurvivors 29 (range 20 to 47) (p < 0.01). The plasma metabolites were grouped
      according to the patients' APACHE II score of the day. There was a positive
      correlation between the severity of metabolic derangement and the APACHE II
      score. The plasma contents of adenosine triphosphate and creatine phosphate were
      depleted with higher APACHE II scores (p < 0.01), whereas creatine and uric acid
      levels increased progressively (p < 0.001). The levels of adenosine, inosine,
      hypoxanthine, and lactic acid were elevated significantly in critically ill
      patients. CONCLUSIONS: Grouping patients with successively higher APACHE II
      scores revealed specific patterns of altered plasma metabolism, possible
      reflecting different levels of tissue adenylate energy charge. However, neither
      the initial individual APACHE II score nor any initial plasma metabolic level had
      any prognostic value in this group of critically ill patients, although the
      deterioration of the physiologic parameters was coexistent with specific
      metabolic changes.

PMID- 9663254
TI  - Impact of altered aminoglycoside volume of distribution on the adequacy of a
      three milligram per kilogram loading dose. Critical Care Research Group.
AB  - BACKGROUND: Sepsis is associated with an increased volume of distribution for
      aminoglycoside antibiotics. As a result of this increased volume of distribution,
      2 mg/kg loading doses have previously been shown to be ineffective in producing
      adequate aminoglycoside peak plasma levels in critically ill patients. The main
      objective of this pharmacokinetic observational study was to determine the
      adequacy of a 3 mg/kg loading dose of gentamicin or tobramycin in attaining an
      initial peak level of 8 micrograms/ml or greater. METHODS: Fifty-three
      consecutive patients given gentamicin or tobramycin for documented or suspected
      life-threatening gram-negative infections were enrolled. Loading doses of either
      aminoglycoside were administered during 30 minutes, and a peak level was obtained
      1 hour after completed infusion. RESULTS: The patient's mean age was 61 +/- 2
      years, with a male/female ratio of 33:20. The loading dose of 3 mg/kg produced 1
      hour peak aminoglycoside levels greater than 8 micrograms/ml in only 50% of the
      patients studied. The calculated aminoglycoside volume of distribution was
      increased by 34%. CONCLUSIONS: An aminoglycoside loading dose of 3 mg/kg is
      inadequate in critically ill patients undergoing operation. The documented
      increase in volume of distribution is principally responsible for the inadequacy
      of this dose. Future studies should use a 4 mg/kg loading dose to maximize
      aminoglycoside bactericidal activity.

PMID- 9663255
TI  - The plasminogen activator/plasmin system is up-regulated after acute necrotizing
      pancreatitis in human beings.
AB  - BACKGROUND: Proteolysis and formation of new extracellular matrix components are
      important mechanisms in tissue remodeling and repair. In this study we analyzed
      the expression and distribution of the urokinase plasminogen activator (uPA), its
      membrane receptor (urokinase plasminogen activator receptor [uPAR]), and its
      inhibitor (plasminogen activator inhibitor-1 [PAI-1]) in acute necrotizing
      pancreatitis in human beings. In addition, we studied the concomitant expression
      of transforming growth factor-beta-1 (TGF-beta 1), which is activated by uPA from
      its precursor and is a potent regulator and stimulator of formation of
      extracellular matrix. METHODS: With immunohistochemistry and Northern blot
      analysis, the expression and cellular distribution of uPA, uPAR, PAI-1, and TGF
      beta 1 were determined in 12 normal pancreata obtained from organ donors and 12
      pancreatic tissues obtained from patients undergoing operation because of
      complications of acute necrotizing pancreatitis. RESULTS: Northern blot analysis
      showed enhanced expression of uPA, uPAR, and PAI-1 in eight of 12, seven of 12,
      and nine of 12 necrotizing pancreatitis samples, respectively, compared with
      normal control samples. In addition, increased TGF-beta 1 mRNA expression was
      present in eight of 12 necrotizing pancreatitis samples. In contrast, amylase
      mRNA expression was markedly decreased in the samples of acute necrotizing
      pancreatitis. Immunohistochemistry revealed elevated uPA, uPAR, and PAI-1
      immunoreactivity in the remaining acinar and ductal cells adjacent to the
      necrotic tissue areas. In contrast, acinar and ductal cells that were located
      farther from pancreatic necrosis exhibited less uPA and uPAR immunoreactivity. A
      similar staining pattern in samples of necrotizing pancreatitis was found for TGF
      beta 1. CONCLUSIONS: Up-regulation of uPA and uPAR, which activate proteolysis,
      might create a milieu that enhances lysis and removal of pancreatic necrosis. The
      increase in TGF-beta 1 might result from the enhanced catalytic conversion of its
      precursors by uPA, which subsequently might stimulate formation of extracellular
      matrix, formation of granulation tissue, and fibrosis.

PMID- 9663256
TI  - A placental-derived tissue matrix as a bowel wall substitute in rats: preliminary
      study.
AB  - BACKGROUND: Occasionally, conventional closure of an intestinal wall defect
      (fistula) is not possible. The development of a biologic material that can be
      used in this setting would solve a significant clinical problem. We hypothesized
      that a collagen patch (connective tissue matrix [CTM]) designed to allow tissue
      regeneration was such a material. METHODS: To test this hypothesis, we performed
      a laparotomy on 75 male Sprague-Dawley rats (experiment A) and removed 25% of the
      anterior cecal wall (1 cm in diameter) to compare intestinal wound healing in
      four situations: (1) control (no repair), (2) fibrin glue repair, (3) primary
      repair, and (4) repair with CTM (human placental bilayer, types I, III, and IV).
      Animals were killed at 1, 2, 4, and 6 weeks. Healing was graded by bursting
      pressure expressed in millimeters of mercury, histologic score (0 to 4), and
      mortality rates. After this, we used the same protocol to remove 80% of the cecal
      wall (1.5 x 2.0 cm) in 19 animals (experiment B) to compare (5) fibrin glue
      repair alone with (6) CTM repair in a situation in which the defect was too large
      for primary repair. RESULTS: CTM repair of a lethal cecal wall defect (experiment
      A) is equivalent to either primary repair or fibrin glue repair. When the defect
      is too large for primary repair (experiment B), repair with fibrin glue also does
      not work. However, in this same setting, CTM repair is successful (p < 0.00001).
      CONCLUSIONS: Intestinal wall defects not suitable for conventional closure can be
      repaired successfully with a collagen patch, with histologic characteristics
      similar to those seen with primary repair.

PMID- 9663257
TI  - Pyruvate improves myocardial tolerance to reperfusion injury by acting as an
      antioxidant: a chemiluminescence study.
AB  - BACKGROUND: There is indirect evidence that pyruvate improves myocardial
      tolerance to ischemia by scavenging oxygen radicals during reperfusion. The
      objectives of this study were to evaluate (1) lucigenin-enhanced
      chemiluminescence (LEC) as a method to measure oxygen radical (OR) production in
      vitro and in vivo and (2) the antioxidant effect of pyruvate during myocardial
      reperfusion. METHODS: LEC was measured in vitro by adding to lucigenin (1)
      increasing concentrations of H2O2, (2) H2O2 and different concentrations of
      catalase, and (3) H2O2 plus pyruvate. Isolated rat hearts perfused with Krebs
      Henseleit-Lucigenin inside a chemiluminescence chamber were subjected to
      equilibration, ischemia, and reperfusion without (control) or with pyruvate.
      Developed pressure, contractility, compliance, and chemiluminescence were
      recorded. RESULTS: In vitro, LEC directly correlated with H2O2 concentrations (r2
      = 0.997) and decreased in the presence of catalase or pyruvate. During myocardial
      reperfusion there was a surge of chemiluminescence that peaked at 4 minutes.
      Pyruvate decreased the initial reperfusion peak (9.8 +/- 0.3 x 10(3) cpm in
      pyruvate group vs 12.4 +/- 0.9 x 10(3) cpm in control; p < 0.05) and the total
      amount of chemiluminescence generated during reperfusion (65.7 +/- 12 x 10(3) in
      pyruvate group vs 117.1 +/- 8.2 x 10(3) counts in control; p < 0.05). Pyruvate
      improved recovery of function after ischemia reperfusion. CONCLUSIONS: LEC is a
      sensitive indicator of H2O2 concentrations and can evaluate the effect of
      antioxidants in vitro. It is a continuous, sensitive, and direct measurement of
      OR production in vivo. LEC is ideal for the evaluation of antioxidant
      interventions and provides direct evidence that pyruvate acts as an antioxidant
      while improving myocardial function during reperfusion.

PMID- 9663258
TI  - Ruptured pancreaticoduodenal artery aneurysms and pheochromocytoma in a pregnant
      patient with neurofibromatosis.

PMID- 9663259
TI  - Specificity of elevated CA 19-9 levels in chronic pancreatitis.

PMID- 9663260
TI  - Gastric stromal tumor stained with CD34 and infected with Helicobacter pylori.

PMID- 9663261
TI  - Intermittent obstruction of the inferior vena cava by congenital anteromedial
      diaphragmatic hernia: an extremely rare case of Budd-Chiari syndrome in an
      infant.

PMID- 9663262
TI  - Bullous pemphigoid after prosthetic vascular graft placement.

PMID- 9663263
TI  - Life-threatening upper gastrointestinal tract bleeding caused by ruptured
      extrahepatic pseudoaneurysm after pancreatoduodenectomy.

PMID- 9663264
TI  - Causes and management of pseudoaneurysms.

PMID- 9663265
TI  - Endoscopic versus radioguided parathyroidectomy.

PMID- 9663266
TI  - Postbulbar duodenal ulceration and stenosis associated with celiac disease.
AB  - The case histories of five patients with celiac disease and postbulbar duodenal
      ulceration and stenosis are presented. Celiac disease was unexpected in three of
      the five patients until endoscopic biopsy revealed villous atrophy. Our findings
      suggest that duodenal ulceration and stenosis may be a more common complication
      of celiac disease than previously thought and may precede the clinical diagnosis
      of celiac disease or occur when there are minimal symptoms and nonspecific
      radiographic findings for the disease.

PMID- 9663267
TI  - Jejunal loop obstruction at the ligament of Treitz: a distinct radiological and
      clinical picture of recurrence after subtotal pancreatectomy.
AB  - Of 99 patients operated on with subtotal pancreatectomy due to ampullary
      carcinoma, five had a local recurrence in the pancreatic bed at the ligament of
      Treitz. The patients all had distinct symptoms: recurrent bouts of fever, general
      malaise, and rapid loss of weight. They had little pain, but all were jaundiced
      in spite of absence of marked compression of the bile ducts. Computed tomography
      or ultrasound could not detect the small, local recurrence that was obstructing
      the jejunal loop 10-15 cm distal to the hepaticojejunostomy, but as an indirect
      sign of the recurrence, the distended small bowel loop proximal to the ligament
      of Treitz was clearly seen in all patients.

PMID- 9663268
TI  - Small bowel varices: report of two cases.
AB  - Two cases of small bowel (S-B) varices associated with portal hypertension, one
      with liver cirrhosis and one with portal thrombus, are reported. Detection of S-B
      varices has been a challenging task and several invasive diagnostic techniques
      have been used for this purpose. However, in our cases, color Doppler sonography
      revealed the S-B varices supplied by the superior mesenteric vein and draining to
      the iliac (one case) or ovarian vein (other case), which helped to establish an
      early appropriate diagnostic and treatment plan.

PMID- 9663269
TI  - Percutaneous transluminal angioplasty in the treatment of chronic mesenteric
      ischemia: results and 3 years of follow-up in 23 patients.
AB  - BACKGROUND: We evaluated the clinical efficacy of visceral angioplasty in the
      treatment of chronic mesenteric ischemia. METHODS: Over a 14-year period, we
      performed percutaneous transluminal angioplasty of 41 occlusive diseases of
      visceral arteries founded by angiography in 23 patients with chronic mesenteric
      ischemia. All but one (fibrodysplasic) stenoses were atherosclerotic, and 13 were
      localized in the ostial tract. Clinical follow-up was evaluated at 2, 6, 12, 24,
      and 36 months (mean follow-up = 27 months). RESULTS: Angioplasty demonstrated a
      residual stenosis of 30% or less in 37 procedures, for a technical success rate
      of 90%. Seventeen of 20 patients had symptom remission after the first treatment,
      for a short-term clinical success of 77%; two patients needed a reangioplasty
      after 2 months, and one was referred for aortomesenteric bypass. During a mean
      follow-up of 27 months (range = 2-36), the clinical success was 88%; 2/15
      patients underwent successful repeat angioplasty at 24 and 36 months, for a 100%
      secondary long-term clinical success. Only two minor complications were
      encountered. CONCLUSION: Although surgical results are undoubtedly positive,
      visceral angioplasty is justified in relation to both the high surgical mortality
      and the low incidence of complications arising from visceral angioplasty.

PMID- 9663270
TI  - Sonographic and Doppler assessment of the inferior mesenteric artery: normal
      morphologic and hemodynamic features.
AB  - BACKGROUND: We wanted to evaluate prospectively the feasibility of sonographic
      and Doppler assessment of the inferior mesenteric artery (IMA) and to provide
      data on its normal morphological and hemodynamic characteristics. METHODS:
      Sonography and Doppler study of the IMA were performed on 116 patients without
      splanchnic vessel pathology. Vessel diameter, systolic, diastolic, and time
      averaged mean flow velocities, pulsatility index values, and flow volumes were
      correlated with patient age (< 50 years vs. > or = 50 years) using the Wilcoxon
      rank-sum test. Findings were verified by splanchnic angiography in 11 cases.
      RESULTS: Technically valid studies were obtained in 103/116 cases (88.8%).
      Flowmetric data showed high peripheral resistance (mean +/- SD: systolic flow
      velocity, 1.41 m/s +/- 0.48; minimal diastolic flow velocity, 0.10 m/s +/- 0.16;
      pulsatility index, 3.49 +/- 0.49). Mean flow volume calculated in 80 cases was
      0.13 L/min +/- 0.06. Older subjects presented significantly higher time-averaged
      mean flow velocities and lower resistance than those younger than 50 years.
      CONCLUSIONS: The success rate for sonographic and Doppler study of the IMA is
      similar to that observed with larger splanchnic vessels. Knowledge of its normal
      characteristics is necessary for recognition of pathological conditions and for
      studies of its physiological behavior.

PMID- 9663271
TI  - Water enema computed tomography (WE-CT) in the local staging of low colorectal
      neoplasms: comparison with transrectal ultrasound.
AB  - BACKGROUND: To determine the accuracy of computed tomography performed with a
      water enema application (WE-CT) in the local staging of low colorectal neoplasms
      and to compare the results with those of transrectal ultrasonography (TRUS).
      METHODS: Forty patients with low colorectal tumors were evaluated prospectively
      by CT with the simultaneous administration of a lukewarm rectal enema (0.5-1.5
      L). Thin slices (5 mm) and intravenous application of iodinated contrast media
      were routinely used. TRUS was performed in 18 patients. Tumor size, location, and
      staging according to the TNM classification of the UICC were registered. Tumors
      were classified as < T3 (T1 or T2) or as T3 or T4. For staging peritumoral lymph
      node metastases on WE-CT, two criteria of positivity were tested: N+ if at least
      one peritumoral node > or 5 mm in diameter was seen (reading A); N+ if at least
      one peritumoral node > or = 5 mm or three peritumoral nodes < 5 mm were
      identified (reading B). RESULTS: For the tumor staging, WE-CT showed a
      sensitivity of 90%, a specificity of 73%, a positive predictive value (PPV) of
      90%, a negative predictive value (NPV) of 73%, and an accuracy of 85%. For TRUS,
      the results were sensitivity of 73%, specificity of 29%, PPV of 62%, NPV of 40%,
      and an accuracy of 39%. Concerning nodal staging with WE-CT, results were
      superior when reading A was used: sensitivity = 84%, specificity = 83%, PPV =
      73%, NPV = 91%, and accuracy = 84%. TRUS showed a sensitivity of 29%, specificity
      of 100%, PPV of 100%, NPV of 67%, and an accuracy of 71%. CONCLUSION: WE-CT is a
      reliable technique for the local staging of low colorectal tumors that can be
      superior to TRUS. For diagnosis of peritumoral metastatic lymph nodes on WE-CT,
      the 5-mm diameter cutoff value is the most appropriate size criterion.

PMID- 9663272
TI  - Total proctocolectomy and ileoanal pouch: the role of contrast studies for
      evaluating postoperative leaks.
AB  - BACKGROUND: To assess the role of contrast enemas for the evaluation of leaks in
      symptomatic and asymptomatic patients after the first stage of restorative
      proctocolectomy. METHODS: We reviewed the findings of 59 contrast enemas in 40
      patients who underwent total proctocolectomy with creation of an ileoanal pouch
      and a proximal diverting ileostomy. Thirty-seven patients initially underwent
      routine contrast studies of the ileoanal pouch, and three underwent contrast
      studies because of suspected fistulas or obstruction. Medical records were also
      reviewed to determine the clinical presentation and course of these patients.
      RESULTS: Of 37 patients who underwent routine postoperative contrast enemas, 33
      (89%) had normal studies, three (8%) had clinically silent leaks (including two
      blind-ending tracks from the ileoanal anastomosis and one from the pouch), and
      one (3%) had pouchitis. In all three patients with unsuspected leaks, ileostomy
      closure was delayed. In two other patients with abdominal pain and fever,
      contrast enemas revealed leaks from the ileoanal pouch and distal ileum,
      respectively. The remaining patient had a contrast enema because of abdominal
      pain and distention; this patient had a distal ileal obstruction due to
      adhesions. CONCLUSIONS: Routine postoperative contrast studies revealed
      clinically silent leaks from the ileal J pouch or ileoanal anastomosis in three
      of 37 patients (8%) after the first stage of restorative proctocolectomy. Our
      findings suggest that routine contrast enema can detect clinically silent leaks
      after this surgery.

PMID- 9663273
TI  - Endoscopic ultrasound and intraductal ultrasound in the diagnosis of small
      pancreatic tumors.
AB  - BACKGROUND: The purpose of this study was to assess the diagnostic value of
      endoscopic ultrasound (EUS) and intraductal ultrasound (IDUS) in the detection of
      small pancreatic tumors. METHODS: EUS was performed in 166 patients with verified
      pancreatic disease. IDUS was performed in 46 patients. A microprobe was
      introduced into the main pancreatic duct through the papilla of Vater using the
      duodenoscope. RESULTS: EUS was valuable in the detection of small pancreatic
      tumors. Ductal adenocarcinomas smaller than 1 cm were demonstrated as a
      hypoechoic mass with a central irregular hyperechoic area. EUS and IDUS were
      useful in the characterization of intraductal paillary tumors (ductectatic
      mucinous tumors). EUS demonstrated nodular excrescences, and IDUS depicted
      papillary proliferation of the duct epithelium, which are characteristic of
      carcinomas and adenomas but not of hyperplasia. Internal architecture of cystic
      neoplasms was clearly depicted by EUS, and differentiation of serous and mucinous
      tumors was readily achieved. A tumor as small as a 5-mm islet cell was
      demonstrated on EUS because islet cell tumors are very hypoechoic. CONCLUSION:
      EUS and IDUS are relatively noninvasive procedures and are useful in the
      detection of small tumors and differentiation of pancreatic diseases.

PMID- 9663274
TI  - Pancreatic cystic neoplasms: the role and sensitivity of needle aspiration and
      biopsy.
AB  - BACKGROUND: The proper evaluation of patients with pancreatic cystic neoplasms
      remains controversial. Although computed tomography (CT) and sonography can
      differentiate the majority of these tumors, needle aspiration and biopsy can be
      helpful in selected patients. The purpose of this study was to (1) determine the
      sensitivity of needle aspiration and biopsy of cystic pancreatic neoplasms, (2)
      assess the complications after needle aspiration and biopsy, and (3) assess the
      indications for needle aspiration and biopsy by using the radiographic appearance
      as a guide. METHODS: The histories, imaging studies, and pathologic specimens of
      18 patients with serous cystadenoma (10 patients) or mucinous cystic tumor (eight
      patients) of the pancreas who also underwent CT-guided (n = 16), sonographically
      guided (n = 3), or intraoperative (n = 4) needle biopsy (n = 23 total biopsies)
      between 1976 and 1996 were retrospectively reviewed. RESULTS: The histologic
      diagnosis of the serous subtype was made with needle aspiration and biopsy in
      five of 10 patients with serous cystadenoma. The histologic diagnosis of the
      mucinous subtype was made with needle aspiration and biopsy in six of eight
      patients with mucinous cystic neoplasms. Of the 23 biopsies performed, one
      patient experienced significant intraperitoneal hemorrhage. Indications for
      needle biopsy include an atypical cystic mass on diagnostic imaging studies,
      confirmation of a serous cystadenoma before observation, and confirmation of
      mucinous cystadenocarcinoma in patients with nonresectable disease. CONCLUSION:
      Needle biopsy and aspiration is a helpful and safe procedure to aid in the
      diagnosis of cystic pancreatic neoplasms before surgery.

PMID- 9663275
TI  - Pancreatic tuberculosis: CT findings.
AB  - BACKGROUND: The purpose of this study was to describe the computed tomography
      (CT) findings in pancreatic tuberculosis (PT). METHODS: We retrospectively
      reviewed the CT features in six patients with PT, three of whom had AIDS.
      RESULTS: Pancreatic lesion masses were found in four patients, small (< 1 cm) low
      attenuation pancreatic nodules in one, and diffuse enlargement of the pancreas in
      one. The pancreatic lesion masses were found in all the non-AIDS patients and in
      one patient with AIDS and were located in the head of the pancreas in two cases
      and involved the body, neck, and head of the gland in the other two. The masses
      showed low attenuation in two cases, soft-tissue attenuation in one, and appeared
      as an infiltrating inhomogeneous lesion with retropancreatic spread, encasing the
      celiac trunk and superior mesenteric artery in one. Low-attenuation
      peripancreatic and/or periportal adenopathies with peripheral rim enhancement
      were found in three cases, and slight bile duct dilatation was evident in four.
      Four patients had disseminated tuberculosis, whereas pancreatic and
      peripancreatic tuberculosis were the sole manifestation of tuberculosis in the
      other two. CONCLUSION: The present data suggest that PT usually appears as a
      nonspecific focal lesion mass in HIV-seronegative patients, whereas there is a
      variable spectrum of CT findings including focal lesion mass, multiple small low
      attenuation pancreatic nodules, or diffuse enlargement of the gland in AIDS
      patients. Low-attenuation peripancreatic and periportal adenopathies with
      peripheral rim enhancement and other data of disseminated tuberculosis are
      ancillary findings that should support a diagnosis of PT.

PMID- 9663276
TI  - MR cholangiopancreatography: comparison between half-Fourier acquisition single
      shot turbo spin-echo and two-dimensional turbo spin-echo pulse sequences.
AB  - BACKGROUND: To compare half-Fourier acquisition single-shot turbo spin-echo spin
      echo (HASTE) magnetic resonance cholangiopancreatography (MRCP) with two
      dimensional turbo spin-echo (2D TSE) MRCP for imaging pancreatobiliary diseases.
      METHODS: Twenty-seven patients with biliary or pancreatic disease underwent MRCP
      on a 1.0-T scanner with a body phased-array coil. A T2-weighted HASTE sequence
      (18 s) and a T2-weighted 2D TSE sequence (45 s) were used during a breath-hold by
      the patient. The source images and maximum intensity projection images of both
      sequences were reviewed independently by two radiologists. RESULTS: Motion
      artifacts were more severely pronounced with 2D TSE sequences than with HASTE
      sequences (p < 0.001). All obstructions and their sites were accurately
      identified with both sequences. Filling defects (calculi) in bile ducts were
      identified in all 22 segments (100%) with HASTE-MRCP, whereas calculi in 19 of 22
      segments (86%) were identified with 2D TSE-MRCP (p = 0.25). Three missed sites on
      2D TSE-MRCP were intrahepatic bile ducts. CONCLUSIONS: HASTE-MRCP is superior to
      2D TSE-MRCP in terms of detecting motion artifacts and visualization of the
      pancreatic ducts. HASTE-MRCP is comparable to 2D TSE-MRCP for visualization of
      the biliary ducts and their obstruction and is superior to 2D TSE-MRCP for
      identification of calculi in intrahepatic bile ducts.

PMID- 9663277
TI  - Paraumbilical vein in the cirrhotic patient: imaging with 3D CT angiography.
AB  - The paraumbilical vein is a common venous collateral in patients with cirrhosis
      and portal hypertension. This pictorial essay demonstrates the use of computed
      tomographic angiography with three-dimensional volume rendering techniques to
      visualize the paraumbilical vein and its relationship to abdominal wall
      collaterals. The unique anatomy and embryology of this vessel is also discussed.

PMID- 9663278
TI  - Diagnosis of fatty infiltration of the liver on contrast enhanced CT: limitations
      of liver-minus-spleen attenuation difference measurements.
AB  - BACKGROUND: We investigated whether liver-minus-spleen (L-S) attenuation
      differences can accurately diagnose fatty infiltration of the liver on contrast
      enhanced computed tomography (CT). METHODS: A group of 78 patients administered a
      fast injection (90-s duration) of 150 mL 60% ionic contrast was compared with 81
      patients given a slow injection (152.5 s). The presence or absence of fatty
      infiltration of the liver was diagnosed by noncontrast CT. RESULTS: The L-S
      attenuation differences varied significantly, depending on both injection rate
      and timing of measurements. For the fast-injection group, the optimal L-S
      threshold for diagnosing fatty infiltration ranged from -43 to -33 Hounsfield
      units (HU) for early (79 s) and late measurements (106 s), respectively. For the
      slow-injection group, the optimal threshold ranged from -31 to -25 HU (80 and 112
      s, respectively). In addition, sensitivity was not very high (range = 0.54-0.71)
      for either injection protocol at any measurement time because of significant
      overlap of L-S values between normal and fatty infiltration patients. Moderate
      and severe fatty infiltration were more reliably diagnosed than mild fatty
      infiltration by this method. CONCLUSIONS: Contrast injection rate and timing of
      measurements significantly influence the optimal L-S threshold for diagnosing
      fatty liver. This limits the clinical usefulness of such measurements.

PMID- 9663279
TI  - Detection of hepatic tumors: arterial-phase MR imaging versus spiral CT
      arteriography.
AB  - BACKGROUND: To compare the utility of arterial-phase magnetic resonance (APMR)
      imaging and spiral computed tomography arteriography (CTA) for detection of
      hepatic tumors. METHODS: Both APMR imaging and CTA were performed in 24 patients
      with liver tumors. APMR imaging was initiated at 25-30 s after an intravenous
      bolus injection of gadolinium-diethylenetriamine pentaacetic acid using the fast
      multiplanar spoiled GRASS technique. CTA was initiated at 3 s after hepatic
      arterial injection of 30-64% nonionic contrast agent. APMR and CTA images were
      separately reviewed retrospectively by two blinded readers. Afterward, matched
      pair was reviewed to determine which had better lesion conspicuity. RESULTS: The
      sensitivities for hepatic tumors were 67.2 and 86.6% in APMR and CTA,
      respectively (p < 0.01). Seven (12.5%) and 21 (23.9%) false-positive lesions were
      seen at APMR and CTA, respectively (NS). Lesion conspicuity was comparable
      between APMR and CTA. CONCLUSIONS: Although APMR imaging is an useful noninvasive
      method to detect hypervascular liver tumors, APMR imaging is still not an
      alternative to CTA with respect to tumor detectability.

PMID- 9663280
TI  - T2-weighted MR imaging for hepatic hemangiomas: comparison of breath-hold and non
      breath-hold turbo spin-echo pulse sequences with phased-array multicoil.
AB  - BACKGROUND: We compared T2-weighted and heavily T2-weighted breath-hold turbo
      spin-echo (TSE) sequences with T2-weighted non-breath-hold TSE sequence to
      evaluate hepatic hemangiomas on magnetic resonance (MR) with a phased-array
      multicoil. METHODS: Twenty-two patients with 27 hemangiomas were studied at 1.0-T
      scanner by using T2-weighted and heavily T2-weighted breath-hold TSE sequences
      (18 s each) and non-breath-hold T2-weighted TSE sequences with use of a phased
      array multicoil. Images were quantitatively analyzed for tumor-to-liver signal
      difference-to-noise ratios (SD/Ns) and tumor-to-liver signal intensity ratios
      (T/Ls) and qualitatively analyzed for tumor conspicuity and motion-induced image
      artifacts. RESULTS: Quantitatively, T2-weighted breath-hold TSE images showed the
      highest SD/Ns among the three sequences, although the differences from the
      heavily T2-weighted breath-hold TSE sequence and the T2-weighted non-breath-hold
      TSE sequence were not statistically significant (p = 0.61 and 0.06,
      respectively). Heavily T2-weighted breath-hold TSE images showed the highest T/Ls
      among the three sequences. The differences from the T2-weighted breath-hold TSE
      sequence and the T2-weighted non-breath-hold TSE sequence were statistically
      significant (p < 0.001). Qualitatively, breath-hold TSE images were superior to
      non-breath-hold TSE images in terms of tumor conspicuity (p < 0.01) and motion
      artifacts (p < 0.01). CONCLUSION: T2-weighted breath-hold TSE sequence is
      superior to T2-weighted non-breath-hold TSE sequence in the evaluation of hepatic
      hemangiomas on MR with a phased-array multicoil.

PMID- 9663281
TI  - Liver transplant rejection: value of hepatic vein Doppler waveform analysis.
AB  - BACKGROUND: To determine whether abnormal hepatic vein Doppler tracings can be
      used to predict liver transplantation rejection. METHODS: A total of 158 hepatic
      vein Doppler tracings were obtained on 93 postliver transplant patients (63
      patients without rejection and 30 patients with biopsy-proven rejection). Hepatic
      vein Doppler tracings were scored according to an established grading system (0 =
      normal triphasic waveform, 1 = dampened waveform, with loss of flow reversal, 2 =
      completely flat waveform). The hepatic vein Doppler tracings were then correlated
      with biopsy findings. RESULTS: In the group of 63 patients without rejection, 124
      Doppler examinations were performed and graded as follows: 0 = 87 (70%), 1 = 31
      (25%), and 2 = 6 (5%). In the group of 30 patients with biopsy-proven rejection,
      34 Doppler examinations were performed and graded as follows: 0 = 16 (47%), 1 =
      14 (41%), and 2 = 4 (12%). The sensitivity of abnormal hepatic vein Doppler
      tracings for detection of rejection was 53% and the specificity was 70%. The
      positive predictive value of an abnormal hepatic vein Doppler tracing was 33% and
      the negative predictive value of a normal Doppler tracing was 84%. CONCLUSIONS:
      Abnormal hepatic vein Doppler tracings are observed in patients with and without
      liver transplant rejection. Abnormal tracings cannot be used to predict liver
      transplant rejection.

PMID- 9663282
TI  - Enhancement patterns of renal masses during multiphase helical CT acquisitions.
AB  - BACKGROUND: To describe the appearance of renal masses during multiphase helical
      computed tomography (CT) acquisition and evaluate the impact of a cortical
      nephrographic phase on diagnosis. METHODS: The CT examinations of 33 patients
      with 37 lesions [18 renal cell carcinomas (RCC), nine solid tumors, 10 cystic
      lesions] were reviewed to characterize renal masses during four phases of CT
      scanning: plain, cortical nephrographic, tubular nephrographic, and pyelographic.
      Two reviewers analyzed all lesions on the complete data set, and a third reviewer
      analyzed three combinations of images separately: (1) plain and tubular
      nephrographic phases, (2) plain and cortical nephrographic phases, and (3) three
      phases combined. Receiver operating characteristics (ROC) curves were generated
      to determine the respective value of each combination in lesion characterization.
      RESULTS: During the cortical nephrographic phase, hyperdensity of solid renal
      masses was 100% specific and 22% sensitive for RCC, whereas combining hyperdense
      and isoattenuating heterogeneous masses was 91% specific and 56% sensitive. ROC
      curves demonstrated a sensitivity of 85%, 90%, 100% for the three combinations,
      respectively, with a constant specificity of 88% for diagnosing RCC. CONCLUSION:
      The cortical nephrographic phase is useful to characterize renal masses and
      should be included in the routine helical CT protocol.

PMID- 9663283
TI  - Uterus didelphys associated with obstructed hemivagina and ipsilateral renal
      agenesis: MR findings in seven cases.
AB  - BACKGROUND: Although a specific syndrome of the uterus didelphys, obstructive
      hemivagina, and ipsilateral renal agenesis had been reported in gynecologic
      literatures, it is not familiar to radiologists. We introduce this syndrome with
      radiological, especially MR findings. METHODS: Imaging findings and medical
      records of seven patients with this syndrome were retrospectively reviewed.
      RESULTS: MR clearly demonstrated uterus didelphys with obstructed hemivagina in
      six of the seven patients. A remaining one showed uterus didelphys with left
      sided hematometra and hematosalpinx who had undergone vaginal septum incision
      prior to the MR. We could also recognize ipsilateral renal agenesis in all five
      patients, in whom renal areas were examined on MR. After vaginal septum
      resection, symptoms disappeared in six patients. We could observe the
      disappearance of the obstructive complications with MR in three patients.
      CONCLUSIONS: MR can do much for the early diagnosis and the prevention against
      further complications of this condition because it can demonstrate the mullerian
      duct anomaly complicated with obstructed hemivagina in detail and even
      ipsilateral renal agenesis.

PMID- 9663284
TI  - Complications of prostate cryosurgery: CT findings in three patients.
AB  - We present the computed tomographic (CT) findings of complications of prostate
      cryosurgery in three patients. One patient had injury to the bladder base and
      rectum, which resulted in ureteral obstruction and vesicorectal fistula. The
      other two patients had urethral injuries. All three patients had CT evidence of
      prostate necrosis. If utilization of prostate cryosurgery increases,
      complications will be encountered more frequently on imaging studies.

PMID- 9663285
TI  - Fibrofatty proliferation of the mesentery in Crohn disease.

PMID- 9663286
TI  - "Bubbly" duodenal bulb in clinically unsuspected or refractory adult celiac
      disease.

PMID- 9663287
TI  - Older drivers' accident risk: conceptual and methodological issues.

PMID- 9663288
TI  - To drive or not to drive: the influence of social factors on the decisions of
      elderly drivers.
AB  - Being able to drive is considered to be an important, if not vital, component of
      mobility in many jurisdictions. From a large population-based health survey,
      carried out in Ontario, Canada in 1990 it is estimated that 37.5% of the
      population aged 80 or older drives a motor vehicle at least once a year. Data
      from the survey have been used to make comparisons of drivers and non-drivers:
      people who drive are more likely to be male, to be married and to report no more
      than one chronic disease. People who do not drive are more likely to live in
      larger households and to report two or more chronic diseases. Although many of
      these factors are clearly related to one another, they exert independent
      associations with whether people drive after other factors have been controlled.
      Drivers and non-drivers have similar frequency of contact with family and friends
      after other variables have been controlled for.

PMID- 9663289
TI  - Why do older drivers give up driving?
AB  - All Finnish license holders aged 70 years (from the cohort born in 1922) who did
      not renew their driver license, and a corresponding comparison group among those
      who did renew their license, were contacted by a mail survey. They were asked
      about their reasons to continue or to stop driving, about their current living
      conditions and health status, and about some aspects of their driving behavior.
      The reasons to stop or to continue driving were different for men and women. Male
      drivers considered more frequently than female drivers the use of private car a
      necessity. Male respondents who did not renew their license (ex-drivers) were
      less healthy than those who did renew their license (drivers). The most
      frequently indicated reason to stop driving among men was deteriorated health.
      However, only 6.9% of the ex-drivers had received professional advice to stop
      driving. For most of these cases, this advice had been given by the physician
      responsible for the treatment of their main illness. The change in health
      condition was related to a shift in driving activity: those still driving were in
      best health, followed by those ex-drivers who stopped driving at the age of 70
      years, while those who had stopped driving at an earlier age had the highest
      number of illnesses and had most frequently experienced a deterioration of their
      health status during the last year. Both male and female ex-drivers reported more
      feelings of stress in traffic and more frequent avoidance of certain traffic
      situations than drivers. Women reported more frequently traffic-related stress
      and avoidance than men as both drivers and ex-drivers.

PMID- 9663290
TI  - Driving avoidance and functional impairment in older drivers.
AB  - The purpose of this study was to examine the association between visual and
      cognitive impairment in older drivers and their avoidance of potentially
      challenging, driving situation. A group of 257 older drivers participated in
      assessments of visual sensory function, eye health and cognitive function
      including the useful field of view test, and completed a structured questionnaire
      on driving exposure and how frequently they avoided challenging driving
      situations. Results replicated earlier studies showing that many older drivers
      limit their exposure to driving situations which are generally believed to be
      more difficult (e.g. rain, night, heavy traffic, rush hour). Furthermore, older
      drivers with objectively determined visual and/or attentional impairments
      reported more avoidance than those free of impairments; those with the most
      impairment reported avoiding more types of situations than other less impaired or
      non-impaired drivers. Older drivers with a history of at-fault crashes in the
      prior five years reported more avoidance than those who had crash-free records.
      Future research should evaluate the potentially beneficial role of self
      regulation in enhancing older driver safety, particularly in those older drivers
      with visual and attentional processing impairments who have elevated crash risk.

PMID- 9663291
TI  - Older drivers fail in intersections: speed discrepancies between older and
      younger male drivers.
AB  - A high percentage of older drivers' accidents occur in intersections when
      entering the traffic or crossing a main road. The problems may be in perception
      or attention, motor performance or inadequate interaction with other road users.
      Attempts to explain older drivers' problems have mostly focused on the properties
      and behaviour of the older drivers only, without considering the interaction
      between older and younger road users. The descriptions of older drivers' problems
      in intersections are usually based on accident data. This study aimed to describe
      the normal behaviour of older drivers, including driving habits, attention
      patterns and interaction with younger drivers. The driving behaviour of young,
      old and middle-aged male drivers was studied using video cameras and observers in
      three T-shaped intersections in Sendai, Japan. The results showed no differences
      in attention behaviour between the age groups as measured with head movements.
      The age groups had different acceleration habits and thus different turning time,
      which also varied depending on whether the vehicle on the main road came from the
      left or the right. Also the outcome of the turning manoeuvre was dependent on
      age. The time margins to the vehicles on the main road were shortest when an old
      driver was turning and a young driver approached on the main road. The time
      margin between the turning driver and the vehicle approaching on the main road
      was clearly shorter when the latter vehicle was a motorcycle than if it was a
      car. The results are discussed in relation to the literature on the risk
      behaviour of old drivers.

PMID- 9663292
TI  - Confidence in, and self-rating of, driving ability among older drivers.
AB  - Active drivers (n = 125) in a representative cohort of older individuals age 77
      years and older in New Haven, Connecticut were interviewed. Confidence in
      different driving situations, self-rating of driving ability, and driving
      patterns were assessed during these in-person interviews. A history of crashes,
      moving violations and being stopped by police was available for approximately the
      past 6 years. Concurrent driving performance was assessed in a subsample (n =
      35). Analyses focused on determining the relationship of confidence and self
      rating of driving ability to: (1) each other; (2) driving patterns; (3) adverse
      driving events; and (4) driving performance. All participants rated themselves as
      being average or above average drivers compared to others their age, with the
      majority rating themselves as above average. Individuals who drove more miles and
      more frequently were more likely to rate themselves better drivers than same-age
      peers. Individuals who rated themselves as "much better" drivers than their peers
      tended to have higher confidence levels than those who rated themselves a "little
      bit better" or the "same" as other drivers. On-road driving performance and
      history of adverse events were not associated with self-ratings of driving
      ability. Confidence was associated with driving frequency and mileage, but not
      age or education. Although men were more likely to drive under risky conditions,
      for those conditions in which each drove, men and women were equally confident.
      No relationship was found between confidence and adverse driving events or
      driving performance. Understanding the relationship of confidence and self-rating
      of driving ability to driving patterns, adverse events and driving performance
      may provide additional insights into identifying older drivers at increased risk
      for problems and formulating intervention strategies to help lower risk.

PMID- 9663293
TI  - Cognitive test performance and crash risk in an older driver population.
AB  - This paper reports on the usefulness of five brief tests of cognitive function
      for identifying older drivers who may be at increased risk of crash involvement;
      it also examines the broader issue of whether impaired cognitive function is
      associated with increased crash risk in the older driver population. Data for the
      study were collected from 3238 drivers aged 65 and older applying for renewal of
      their North Carolina driver's license. The specific cognitive assessments
      examined include the Trail Making Test parts A and B, the Short Blessed
      Orientation-Memory-Concentration test of cognitive impairment, a modification of
      the American Association of Retired Persons 'Reaction Time' test, and a timed
      Traffic Sign Recognition test. Information on crash involvements during the 3
      year period prior to testing was obtained by linkage with the North Carolina
      driver history file. Although the individual tests were not found to be
      particularly effective screening tools for identifying subsets of high risk
      drivers, cognitive test performance remained significantly associated with crash
      risk even after controlling for driver age, race and measures of driving
      exposure. Drivers who scored in the lowest 10% on the cognitive tests were
      approx. 1.5 times more likely to be in crashes than were drivers who scored in
      the highest 10%. Implications for the counseling and licensing of older drivers
      are discussed, along with recommendations for future research.

PMID- 9663294
TI  - Assessing medically impaired older drivers in a licensing agency setting.
AB  - An exploratory study is being conducted jointly by the California Department of
      Motor Vehicles and the National Highway Traffic Safety Administration to develop
      a licensing agency assessment battery for elderly drivers with dementia or other
      aging-related medical conditions. A preliminary battery of nondriving tests and
      road tests is described; test results for a small pilot sample are presented, and
      the tests are evaluated in terms of their utility for detecting functional
      impairment and predicting driving performance. Some considerations that shape
      construction of a test battery for licensing agency use are discussed in relation
      to these goals and the givens of a driver licensing environment.

PMID- 9663295
TI  - A comparative approach to identify unsafe older drivers.
AB  - The identification of unsafe older drivers is a current and important challenge.
      In the present research, a comparative approach was used in which the on road
      driving errors and expert evaluations of older drivers with clinically
      significant declines in mental abilities (N = 155) were compared to the errors
      and evaluations of a normal elderly control group (N = 68) and a normal younger
      control group (N = 30). The results indicate that the conventional criteria used
      in North America for licensing new drivers is inappropriate for license removal
      in experienced drivers. The results also indicate that hazardous errors were the
      single best indicator of membership in the group of older drivers with clinical
      impairment. This group also differs from the two normal control groups on turn
      positioning errors, minor positioning errors and overcautiousness. All groups
      differ from each other on scanning errors. A regression analysis further
      indicated that the five driving errors listed above accounted for over 57% of the
      variance associated with global ratings provided by expert driving instructors.

PMID- 9663296
TI  - Impairments of some cognitive functions are common in crash-involved older
      drivers.
AB  - The relationship between limitations in different cognitive functions, measured
      with a neuropsychological test battery, and moving traffic violations among older
      drivers was investigated. Thirty-seven drivers aged 65 years or more, with
      temporarily suspended driving licenses (suspended drivers) were identified 23
      were crash-involved and 14 were not. When compared to 31 controls with clean
      driving records, crash-involved suspended drivers performed less well on tests of
      visuoconstructive ability (p = 0.008), psychomotor speed (p = 0.019) and
      visuospatial memory (p = 0.036). Non-crash-involved suspended drivers did not
      differ from controls. A combination of three tests (of visuoconstructive ability,
      visuospatial memory and verbal episodic memory) succeeded in correctly
      classifying 65.2% of the crash-involved suspended drivers. The results support
      the idea of cognitive decrements as an important causal factor in crashes of
      older drivers.

PMID- 9663297
TI  - Age related changes in drivers' crash risk and crash type.
AB  - Age and gender differences in the rates of crash involvement of Western
      Australian drivers were examined using the Road Injury Database of the Road
      Accident Prevention Research Unit at the University of Western Australia. The
      population examined was all drivers of cars, station wagons and related vehicles
      involved in property damage, injury and fatal crashes reported to the police in
      Western Australia from 1 January 1989 to 31 December 1992. It was found that
      drivers aged < 25 years were involved in ca 35% of crashes, compared with 3% for
      drivers 70 years and over. Drivers under 25 years had the highest rates on a
      population and licence basis, but when the distance travelled was taken into
      account, rates of crash involvement for the 75 or more age group were as high as
      those of the youngest age group. Females had higher rates of crash involvement
      than males in all age groups. Drivers over 70 years were involved in relatively
      more crashes involving fatalities and hospital admissions than younger drivers,
      although the number of such crashes was small. The youngest groups of drivers had
      proportionately more single vehicle crashes, drivers 30-59 years had more same
      direction crashes, and drivers over 60 years, particularly those over 75 years,
      had more direct and indirect right angle crashes. There were also age related
      patterns in the movements associated with these crashes. Drivers under 30 years
      were associated with swerving and swinging wide, drivers 30-59 years were stopped
      at the time of the crash disproportionately often, and drivers over 60 years were
      associated with turning movements. The percentage of crashes in daylight ranged
      from ca 64% for drivers under 20 years to a maximum of over 90% for those 80
      years and over. These patterns are consistent with changes in exposure to risk of
      crash involvement with age, and also with changes in ability, experience and
      psychological function, which are also related to age.

PMID- 9663298
TI  - Traffic-related injury hospitalizations among California elderly, 1994.
AB  - Traffic-related injuries among the elderly are a growing concern in most
      developed and many developing countries. To better understand injuries sustained
      by the elderly in the traffic environment, hospitalizations for traffic-related
      injuries among those aged 64 and over in California in 1994 were examined to
      determine incidence and characterize injuries. Both injury incidence and injury
      severity increased as age increased over 64. Males were more likely to be injured
      as drivers of motor vehicles, but females were more likely to be injured as
      passengers. Fractures and internal injuries represented 72.3% of all primary
      diagnoses, and total hospital charges exceeded $140 million. Efforts to reduce
      traffic-related injuries in the elderly and to reduce injury severity will be
      increasingly important as the elderly comprise a larger proportion of the
      population.

PMID- 9663299
TI  - Scientific publication is dominated by First World countries.

PMID- 9663300
TI  - Plasma vitamins A, C and E in the general population of Singapore, 1993 to 1995.
AB  - The National University of Singapore Heart Study measured cardiovascular risk
      factors, including selected plasma vitamins, on a random sample of the general
      population aged 30 to 69 years. Plasma vitamins A and E were normal and similar
      by ethnic group. Mean plasma vitamin A levels were: Chinese (males 0.68 and
      females 0.52 mg/L), Malays (males 0.67 and females 0.54 mg/L), and Indians (males
      0.66 and females 0.51 mg/L). Mean plasma vitamin E levels were: Chinese (males
      12.6 and females 12.6 mg/L), Malays (males 13.6 and females 13.3 mg/L), and
      Indians (males 12.9 and females 12.8 mg/L). No person had plasma vitamin A
      deficiency (< 0.01 mg/L) and only 0.1% had vitamin E deficiency (< 5.0 mg/L). In
      contrast, plasma vitamin C was on the low side and higher in Chinese than Malays
      and Indians. Mean plasma vitamin C levels were: Chinese (males 6.3 and females
      8.4 mg/L), Malays (males 5.1 and females 6.4 mg/L), and Indians (males 5.7 and
      females 6.9 mg/L). Likewise, the proportions with plasma vitamin C deficiency (<
      2.0 mg/L) were lower in Chinese (males 14.4 and females 0.7%), than Malays (males
      19.7 and females 7.2%), and Indians (males 17.8 and females 11.0%). Relatively
      low levels of plasma vitamin C may contribute to the high rates of coronary heart
      disease and cancer in Singapore. In particular, lower plasma vitamin C in Malays
      and Indians than Chinese may contribute to their higher rates of coronary heart
      disease. However, plasma vitamin C does not seem to be involved in the higher
      rates of cancer in Chinese than Malays and Indians. The findings suggest a
      relatively low intake of fresh fruits and a higher intake is recommended. Also,
      food sources of vitamin C may be destroyed by the high cooking temperatures of
      local cuisines, especially the Malay and Indian ones.

PMID- 9663301
TI  - Population-based mammographic screening in Singapore: what are participants'
      views?
AB  - Mammographic screening for breast cancer has been shown to be an effective tool
      for reducing mortality from the disease in many studies in the West, if high
      technical quality and acceptance by the target population are achieved. The
      objective of the Singapore Breast Screening Project was to determine if the same
      results could be obtained among local women by inviting a random sample of 69,500
      women aged 50 to 64 years for a screening mammogram over two years. To date, the
      compliance rate among the women invited has been 41.7%. The objective of the
      present substudy was to determine participants' views on the accessibility and
      acceptability of organised mammographic screening. Of the three hundred women
      interviewed, 85% were satisfied with the information given prior to the visit,
      while 67% needed to change the original appointment given. The majority were
      satisfied with aspects of the visit such as waiting time, privacy and explanation
      given during the test. However, 35.1% reported at least moderate discomfort
      during mammography. A substantial proportion (39.7%) of attenders felt that there
      was very little hope of cure even if cancer was detected early. When asked the
      most important reason for attending, most indicated they had taken the
      opportunity for a free check-up to be assured they were well. Almost all (95.7%)
      reported a willingness to be screened again, but most would not be willing to pay
      for a mammogram at the current rates.

PMID- 9663302
TI  - Non-diagnostic smears in aspiration cytology of palpable breast lumps.
AB  - The cytologic diagnoses of a wide variety of breast diseases have been described
      in the literature and cytologic appearances of some of these are not
      characteristic. Technical problems during aspiration and smear preparation
      influence the final diagnosis, therefore, even at best hands a non-diagnostic
      category is to be expected. The objectives of this study were to determine the
      frequency of non-diagnostic reports and to assess the source of indecisiveness.
      This study is based on a retrospective analysis of breast aspirates signed out by
      the first author over a period of 18 months. The smears with non-diagnostic
      reports were correlated with the available histologic follow-up to identify the
      problem area. Forty-eight (9.1%) out of the 527 samples were non-diagnostic and
      within the recorded range of 6.9% to 20%. Of those 48 in the non-diagnostic
      category, 30 (62.5%) had histological follow-up. There were 11 (36.7%) malignant
      lesions and 19 (63.3%) benign lesions. In 23 cases (77%) pure interpretative
      problems and in 3 cases (10%) pure technical problems were responsible for the
      non-diagnostic reports. In 4 cases (13%) both factors contributed to the non
      diagnostic report. Thirteen of the 30 (43%) lesions were cytologically suspected
      to be malignant. Of these 13.9 (69%) were found to be malignant while only 4 were
      benign; thus non-diagnostic but suspicious lesions are more likely to be
      malignant. The commonest cytologic features responsible for problems at
      interpretation were high cellularity (37%), cell discohesion (30%), large nuclei
      and nucleoli (30%) and the small size of the cells (40%). Inadequate or low cell
      yield (86%), inadequate clinical history (14%) and poor staining (14%)
      contributed to technical problems. The cytologic diagnosis of breast lesions such
      as fibromatosis, complex sclerosing lesions, papillary lesions, angiosarcoma and
      low nuclear grade in situ and invasive carcinomas can be difficult and the
      cytologic criteria for these diagnoses need further evaluation.

PMID- 9663303
TI  - Contrast-enhanced magnetic resonance imaging of the internal auditory canals and
      posterior fossa.
AB  - A retrospective review of 314 cases of contrast-enhanced magnetic resonance
      imaging (MRI) of the posterior fossa and internal auditory canals was carried out
      correlating the presenting symptoms with the scan findings. 7.2% of the cases
      showed findings on the MRI which could account for the patients' symptoms.
      Patients with sensorineural hearing loss were more likely to have a positive scan
      than those presenting with vertigo and/or tinnitus without hearing loss. Acoustic
      schwannoma was the most common lesion detected. Labyrinthine lesions e.g.
      cochlear schwannoma, labyrinthitis, congenital labyrinthine abnormality, and
      central lesions e.g. multiple sclerosis, brainstem glioma were some of the other
      lesions detected.

PMID- 9663304
TI  - Percutaneous needle aspiration in the treatment of hepatic abscess: factors
      influencing patients' outcome.
AB  - Sixty-four consecutive cases of hepatic abscess diagnosed over a 6-year period
      and all treated by ultrasound-guided percutaneous needle aspiration and systemic
      antibiotics were retrospectively reviewed to ascertain factors influencing the
      outcome in these patients. The 64 patients had in total 101 liver abscesses which
      averaged 4.7 cm in diameter. Two patients (3.1%) required surgery for associated
      biliary tract disease. Five patients (7.8%) died from septicaemia and/or serious
      condition or malignancy. The remaining 57 patients (89.1%) were successfully
      treated--45 cases (70.3%) showed fully-resolved abscess/es after a mean period of
      69.9 days after initial aspiration; 12 patients (18.8%) showed markedly-shrunken
      abscess cavity size over an average of 30.7 days and all were asymptomatic on
      discharge from hospital. No correlation was demonstrated between number of
      abscesses and successful patient recovery--42 of 46 patients (91.3%) with
      solitary hepatic abscess recovered, 6 of 8 patients (75.0%) with 2 abscesses and
      9 of 10 patients (90.0%) with more than 2 abscesses were successfully treated. No
      correlation was detected between abscess size and number of aspirations required,
      majority of abscesses (73.3%) requiring no more than two aspirations irrespective
      of their sizes. Of the 57 patients cured, no significant correlation between
      abscess size and degree of abscess healing was evident. Our results demonstrate
      the effectiveness of percutaneous needle aspiration and it should be considered a
      first-line treatment in the management of liver abscess, irrespective of their
      number and sizes.

PMID- 9663305
TI  - Portable chest radiography: comparison of high-resolution digital displays with
      laser printed digital film.
AB  - Computed radiology is a radiographic imaging technology that generates a
      conventional radiographic image in digital form. The image can be recorded on a
      laser sensitive film or archived to a digital storage device and displayed on a
      video monitor. This study was performed to evaluate the adequacy of reporting
      digitised images directly from the workstation. The test set consisted of
      portable chest images of 55 patients from the cardiothoracic intensive care unit.
      Normal structures and nine abnormalities were pre-selected for analysis. The
      radiographs and images on the video display were reviewed on two separate
      occasions, six months apart by two independent readers. No clinical details were
      supplied and the intraobserver and interobserver agreement were assessed using
      Kappa statistics. The overall results indicated that direct reporting from the
      workstation was as reliable as reporting from the laser printed copies.

PMID- 9663306
TI  - Soft tissue cover in compound and complicated tibial fractures using
      microvascular flaps.
AB  - This is a retrospective review of the use of microvascular flaps in the salvage
      of severely injured lower limb. From January 1992 to December 1994, we treated 10
      patients using 10 microvascular flaps; 8 patients with Type III compound tibial
      fractures and 2 patients with infected implants following internal fixation of
      comminuted tibial fractures. The size of soft tissue defect ranged from 6 x 3 cm
      to 20 x 10 cm. One patient had a 6 cm bony defect. Soft tissue cover was achieved
      in 9 patients using microvascular muscle flaps with meshed split skin grafts and
      1 patient using a scapula osteocutaneous flap. They were performed within 5 to 27
      days following injury or removal of implants (mean 18 days). All the
      microvascular flaps were successful (100%). One re-exploration was performed. The
      mean period of hospitalization following microsurgical flap cover was 16.8 days.
      Eight out of 10 patients were followed up for a mean period of 48 months. All the
      8 lower limbs were successfully salvaged. Three out of 8 patients (37.5%) had
      chronic osteomyelitis which required sequestrectomy and bone grafting. No
      amputation was necessary. Two patients required adjunctive cancellous bone
      grafting to accelerate bony union. Six out of 8 patients (75%) achieved bony
      union and full weight bearing capacity. The use of microvascular flap in
      achieving soft tissue cover plays an important role in the salvage of severely
      traumatized lower limb. Microvascular muscle flap is preferred when only soft
      tissue defect is present. Successful soft tissue cover facilitates secondary bone
      grafting procedures. Although the timing of surgery per se does not adversely
      affect the success rate of microvascular flaps, delayed soft tissue cover is
      associated with a high chronic infection rate (37.5%). An adequate surgical
      debridement is crucial in reducing the complication of deep infection.

PMID- 9663307
TI  - Double level fractures of the femur treated with closed intramedullary nailing.
AB  - The treatment of segmental multilevel fractures of the femur is problematic. Open
      methods of fracture fixation which strip the soft tissue attachments from the
      bone cause devascularisation of the middle segment. Mechanical fixation using 2
      separate plates results in a stress riser. The use of closed intramedullary nail
      addresses some of the problems in this difficult group of fractures, preserving
      the soft tissue envelope and eliminating stress risers. However, vascularity of
      the middle segment may still be compromised. Six cases of fractures of the femur
      that were segmental in nature or associated with a fracture around the hip were
      treated with a closed intramedullary locked nail. The average operating time was
      123 minutes and there were no infections. Average time to union was 7.2 months.
      Two cases required re-operation, one to correct a residual internal rotation
      deformity and one required dynamisation to eliminate the gap at the fracture
      site.

PMID- 9663308
TI  - The role for preoperative localisation techniques in surgery for
      hyperparathyroidism.
AB  - Preoperative localisation procedures in primary hyperparathyroidism have been
      associated with advantages like decreased operative dissection, shorter operating
      time and in some series, lower morbidity and mortality. However, successful
      identification of parathyroid glands exceeding 90% is achievable at surgery
      without preoperative localisation studies. Sixty-nine patients who underwent
      parathyroidectomy at the Department of Surgery, Singapore General Hospital,
      between March 1990 and July 1996 were analysed to determine the role of
      preoperative localisation techniques. Preoperative localisation of parathyroid
      glands consisted of computed tomographic (CT) scan in 66.7% of patients,
      technetium99 sestamibi scan in 23.2%, ultrasound in 15.9% and angiographic
      localisation in 4.3% of the patients. In the 28 end stage renal failure patients
      who were operated for progressive renal osteodystrophy, 6 had preceding renal
      transplants. The success of identifying parathyroid glands at operation in these
      28 patients was independent of CT scan findings. CT scan was correct in only 6%
      of patients while surgical exploration had a success rate of 100%. Of the 41
      patients with primary hyperparathyroidism, the success of CT scan in identifying
      enlarged parathyroid glands was 41.4% compared to 91.6% via surgical exploration.
      Furthermore, CT scan was not able to discriminate between superior and inferior
      parathyroid glands. Preoperative Tc-99m sestamibi scan and ultrasound correctly
      localised pathologic parathyroid gland in 40% and 18.2% of the patients,
      respectively. Therefore, the use of preoperative imaging to localise parathyroid
      glands before the intended exploration was found not to be useful in our series.

PMID- 9663309
TI  - The investigation and management of thyroid nodules--a retrospective review of
      183 cases.
AB  - The management of the patient with a thyroid nodule remains a clinical challenge
      because of its risk of malignancy. This is a retrospective audit of 183 patients
      undergoing thyroidectomy for thyroid nodules at the Queen Elizabeth Hospital,
      Hong Kong, in 1994. The history, physical examination and investigations done
      were charted and analysed against the final histopathology of the specimens. Age,
      sex, symptom duration and nodularity were not associated with malignancy
      statistically, whereas a nodule hard in consistency was shown to be associated
      with malignancy (P < 0.05). The sensitivity and specificity of ultrasonography,
      radionuclide scan and fine-needle aspiration cytology (FNAC) were 71% and 57%,
      50% and 43%, and 93% and 60%, respectively. Hence, history and physical
      examination are unreliable for detecting malignant thyroid nodules and FNAC is
      mandatory. FNAC is superior to ultrasonography or radionuclide scan for
      evaluating thyroid nodules and should be used as the initial investigation.

PMID- 9663310
TI  - Phyllodes tumour: an update of 40 cases.
AB  - This is a retrospective study of 40 cases of phyllodes tumour treated at the
      National University Hospital since 1985. The mean age of presentation was 37.8
      years, with a range of 15 to 58 years [standard deviation (SD) 11.22 years].
      Ninety per cent of the patients were premenopausal. The mean size of tumours was
      52 mm, with a range of 10 to 220 mm. Preoperative diagnosis was correct in only
      five patients, the lesion most commonly being mistaken as a fibroadenoma. Initial
      surgical treatment was by simple excision in 80% of cases. Histologically, the
      ratio of benign, intermediate and malignant tumours was 82.5%, 12.5% and 5%
      respectively. Recurrences occurred in only four patients (10%), all of whom were
      initially treated by simple excision. The diagnosis of phyllodes tumour continues
      to be difficult even with newer modalities of preoperative investigations,
      resulting in simple excision as initial treatment of these tumours. Expectant
      follow-up should be continued for these patients, with wide excision of future
      recurrences.

PMID- 9663311
TI  - A retrospective review of patients with clinically definite multiple sclerosis.
AB  - Multiple sclerosis (MS) is an uncommon disease in Singapore. We retrospectively
      reviewed our experience from a large single medical institution to identify
      prominent clinical features and forms of this disease. Of the 21 patients entered
      into the study, 10 patients developed optic-spinal symptoms over the course of
      their illness. None of these patients with optic-spinal symptoms had Devic's
      disease. Unusual clinical manifestations included paroxysmal symptoms either at
      presentation or during the course of their illness in 3 patients. While
      cerebrospinal fluid oligoclonal bands were present in only 4 patients, the
      majority of patients had abnormal neurophysiology and neuroimaging studies. Due
      to the presence of autoimmune markers in a significant number of cases, we
      recommend that as part of the initial evaluation for MS, an underlying collagen
      vascular disorder should be excluded.

PMID- 9663312
TI  - Haematuria in the diagnosis of urinary calculi.
AB  - The aims of this study were to compare the sensitivity of urine dipstix (Combur 9
      test) versus urine microscopy in detecting haematuria and to determine the
      proportion of patients with renal or ureteric colic due to urinary calculi who
      have haematuria. This is a prospective study of 122 patients presenting to an
      emergency department in a tertiary teaching hospital with symptoms suggestive of
      renal or ureteric colic. The same urine specimen tested using dipstix was sent
      for urine microscopic examination for haematuria, after which a plain radiograph
      of the kidneys, ureter and bladder was done. An early intravenous urogram was
      done (delay of an average of 4 days). Telephone interviews were done to determine
      whether any calculi had been passed. Urine dipstix detected haematuria in 95.4%
      [95% confidence intervals (CI) 87.1% to 100.0%] of patients with urinary calculi,
      whilst urine microscopy detected haematuria in 70.8% (95% CI 58.2% to 92.6%).
      This study showed that urine Combur 9 is more sensitive than urine microscopy in
      detecting haematuria. The combined use of urine Combur 9 and microscopy does not
      increase the sensitivity of detecting haematuria. In the absence of haematuria on
      urine Combur 9 for suspected ureteric colic, alternative diagnoses should be
      considered.

PMID- 9663313
TI  - Otitis externa--the clinical pattern in a tertiary institution in Singapore.
AB  - Otitis externa is a common condition in the tropics. Most of the data related to
      the condition have arisen from Western sources. Locally, the aetiology and the
      pathogens identified have not been systematically studied. A prospective study
      involving 107 patients was conducted. Otomycosis was frequently encountered.
      Coagulase negative Staphylococcus and Aspergillus niger were the most common
      bacteria and fungus cultured respectively. Gentamicin and polymyxin B were the
      most effective topical agents against Pseudomonas aeruginosa. Self-cleaning of
      the ears was the most common predisposing factor.

PMID- 9663314
TI  - Are antacids necessary as routine prescriptives with non-steroidal anti
      inflammatory drugs?
AB  - In Singapore, there exists a local habit to routinely prescribe antacids with non
      steroidal anti-inflammatory drugs (NSAIDs) perhaps in the belief that
      gastrointestinal (GI) symptoms and complications are common, and that antacids
      protect from them. We prospectively studied 140 adults in an orthopaedic clinic
      who were prescribed a short course of NSAIDs (1 to 4 weeks) without antacids to
      determine the frequency and severity of GI symptoms. Symptomatic patients were
      then given antacids to determine their effect on the GI symptoms and followed up
      by telephone interview. These patients had mild inflammation, soft tissue
      rheumatism, injury or degenerative disease. All were otherwise well with no known
      peptic ulcer disease or major illness and were not on ulcerogenic drugs. Only 13
      (9.3%) had significant GI symptoms, of which 6 (4.2%) of the total took antacid
      and 5 (3.5%) had partial or total relief. In this study, GI symptoms were not
      common with short course NSAIDs in otherwise well patients. Antacids may afford
      symptomatic relief for GI symptoms. However, because antacids may offer no
      significant protection against NSAID-induced peptic ulcer, may dangerously mask
      symptoms of GI irritation, may be troublesome to take and costly on a large
      scale, we should stop routine prescription of antacids in patients requiring only
      short-term NSAIDs and not at risk for peptic ulcer disease.

PMID- 9663315
TI  - Survey of aerobic bacterial infections in paediatric surgical intensive care unit
      patients.
AB  - Infections cause a significant amount of morbidity and mortality in paediatric
      surgical patients requiring intensive care. The study aims to describe the
      epidemiology of infection among these patients, to correlate the source of
      infection with the underlying medical condition, and to determine the antibiotic
      sensitivity pattern of the organisms. Through a retrospective review over a
      period of one year, 133 cases were analysed. The overall incidence of infection
      was 35%. Those who had emergency surgery had the highest infection rate (47%).
      Respiratory tract infections were the commonest source of infection, and were
      associated with ventilator therapy rather than the underlying medical condition.
      The Enterobacteriaceae were the most common isolates seen. From antibiotic
      sensitivity tests, the empirical antibiotics of choice are gentamicin for
      suspected gram-negative infection and vancomycin for severe infections where
      methicillin-resistant Staphylococcus aureus is a likely cause. A high rate of
      resistance to ampicillin was seen and its use as a first-line monotherapy drug
      should be discontinued in our patient population.

PMID- 9663316
TI  - The global pandemic of dengue/dengue haemorrhagic fever: current status and
      prospects for the future.
AB  - Dengue/dengue haemorrhagic fever has been one of the most important resurgent
      tropical diseases in the past 17 years, with expanding geographic distribution of
      both the viruses and the mosquito vectors, increased frequency of epidemics, the
      development of hyperendemicity (co-circulation of multiple virus serotypes) and
      the emergence of dengue haemorrhagic fever in new areas. This paper briefly
      reviews the changing epidemiology of dengue, discusses some of the factors
      responsible for the recent resurgence, and reviews the current options for
      reversing the trend of emergent disease.

PMID- 9663317
TI  - Epidural analgesia in obstetrics.
AB  - An ideal analgesic for labour would preferably be non-invasive, as effective as
      spinals and epidurals without their attendant complications and is safe to mother
      and child and should not complicate the labour process. Analgesia for labouring
      women ranges from the use of opioid injections to invasive methods, chiefly
      epidural injections. Each has its advantages and drawbacks. This article provides
      a review of analgesic methods and techniques for labouring women. It focuses
      mainly on the role of epidurals, how it is utilised by anaesthetists and the
      differing methods of drug delivery through the epidural route. It discusses
      various concoctions of local anaesthetics and adjuvants used. The epidural route
      is probably the most effective and most commonly used invasive route for
      achieving analgesia during labour. Local anaesthetics of varying concentrations
      are administered as intermittent boluses or as a continuous infusion. Adjuvant
      drugs are able to enhance the quality and duration of the analgesia. Opioids
      including fentanyl and sufentanil, and clonidine are discussed. The use of
      patient-controlled epidural analgesia and combined spinal-epidural analgesia are
      reviewed. Ambulatory or mobile epidurals are increasingly popular. They are known
      to improve maternal satisfaction because of preservation of motor power.
      Ambulation may help with cervical dilatation and engagement, and abolition of
      backpain, among other advantages. This article describes the methods of
      establishing mobile epidurals and offers guidelines on safe ambulation and
      contraindications to its use.

PMID- 9663318
TI  - A review of the role of magnetic resonance imaging in the evaluation of shoulder
      impingement syndrome and rotator cuff tendon tears.
AB  - The objective of this paper is to present a review of the role of magnetic
      resonance imaging in the evaluation of shoulder impingement syndrome and rotator
      cuff tendon tears. This imaging modality is effective in demonstrating both the
      soft tissue and bony abnormalities associated with structural shoulder
      impingement which include subacromial-subdeltoid bursitis, supraspinatus
      tendinopathy, rotator cuff tendon tears, subacromial osteophytic spurs and
      acromioclavicular joint capsular hypertrophy and osteophytosis. The detection of
      a subacromial osteophytic spur is considered specific for shoulder impingement
      syndrome. The 3 most accurate magnetic resonance imaging signs of a full
      thickness supraspinatus tendon tear reported are: tendon discontinuity,
      musculotendinous junction retraction and supraspinatus tendon thinning. The most
      specific sign is tendon discontinuity and the most sensitive is subacromial
      subdeltoid bursal fluid.

PMID- 9663319
TI  - Interventional electrophysiology and its role in the treatment of cardiac
      arrhythmia.
AB  - Cardiac arrhythmias can present as benign ectopics or as life-threatening
      arrhythmias and sudden cardiac death. Clinical cardiac electrophysiology is the
      study of the electrophysiology of the heart and all aspects of management of
      cardiac arrhythmias. The invasive electrophysiological study was initially purely
      diagnostic, but recent advances in technology has allowed us to intervene and
      hence the term interventional electrophysiology. The interventional therapies
      include permanent pacing for bradyarrhythmias, arrhythmia surgery for
      arrhythmias, percutaneous catheter ablation and implantable devices for
      tachyarrhythmias. The treatment of bradyarrhythmias with permanent pacemaker
      implantation represents the first interventional therapy for patients with
      cardiac arrhythmias. From 1973 to June 1996, a total of 791 pacemakers have been
      implanted at the Singapore General Hospital. Previously, patients with
      tachyarrhythmias could only be cured by open heart surgery utilising
      intraoperative map guided surgery and ablation of the arrhythmia. Only 17
      patients with supraventricular tachycardia (SVT) and 3 patients with VT have
      undergone this procedure. Catheter ablation has completely revolutionised the
      treatment of these patients. From October 1991 until December 1996, 860 patients
      have undergone radiofrequency (RF) catheter ablation for SVT and non-ischaemic
      VT. Ninety-eight per cent of the patients with SVT have been successfully ablated
      and 94% of the patients with VT were successfully ablated. RF ablation has become
      the technique of choice to cure patients with recurrent paroxysmal SVT due to AV
      re-entrant tachycardia using an accessory pathway, AV nodal re-entrant
      tachycardia, atrial tachycardia and atrial flutter. It is also used for AV nodal
      ablation followed by pacemaker insertion or AV nodal modification in patients
      with poorly controlled atrial fibrillation. Patients with idiopathic non
      ischaemic VT arising from the left ventricle or right ventricular outflow tract
      can similarly be cured. For all these patients, RF ablation offers curative
      therapy, thus eliminating recurrent symptoms, life-threatening attacks,
      tachycardia cardiomyopathy and need for life-long drug therapy. For patients with
      resuscitated sudden cardiac death or at high risk for sudden death, the
      implantable cardioverter defibrillator (ICD) is the only technique that has
      significantly improved survival from sudden cardiac death. Since August 1992, 11
      patients have had the ICD implanted, with 9 surviving. The 2 deaths were due to
      cardiac failure and not to sudden death. Thus the ICD can prevent sudden death,
      but the main limitation is the cost of the device and it is not suitable in
      patients who have severe heart failure. In conclusion, interventional
      electrophysiology represents a tremendous leap forward in the management of
      cardiac arrhythmias. With catheter ablation, it offers a safe curative therapy
      for patients with recurrent SVTs and VTs and with the ICD, prevents sudden
      cardiac death in patients who have been resuscitated from it or who are at risk
      for it. The future will see us improving our success in ablating patients with
      monomorphic ischaemic VT and even atrial fibrillation, and the role of
      prophylactic ICDs in high risk patients will be better defined.

PMID- 9663320
TI  - Verrucous haemangioma--a case report.
AB  - Verrucous haemangioma is an uncommon skin lesion which increases in size and also
      evolves in appearance with time. Early diagnosis is important so that surgical
      treatment can be instituted early for better cosmetic results. Its similarities
      and differences to angiokeratoma circumscriptum are also highlighted, and the
      importance of distinguishing the two in terms of management is discussed.

PMID- 9663321
TI  - Recurrent gigantic pyogenic granuloma disturbing speech and mastication: a case
      report and literature review.
AB  - A case of gigantic pyogenic granuloma with three recurrences in the lower
      anterior gingiva is presented. Surgical wide excision of the lesion is the
      treatment of choice. The tumour must be excised down to the periosteum and the
      irritants around it removed to avoid recurrence. A contributing factor to the
      gigantic lesion is hormonal changes during pregnancy. Long-term review for 18
      months after the third surgery showed no evidence of recurrence at the surgical
      site.

PMID- 9663322
TI  - Trilateral retinoblastoma--a case report.
AB  - A sporadic case of trilateral retinoblastoma in a male child of 20 months is
      described using clinical and imaging approaches. Attempts were made to find out a
      tumour marker by analysing human chorionic gonadotrophin (hCG), alpha-feto
      protein (AFP), carcinoembryonic antigen (CEA), and lactic dehydrogenase (LDH) in
      blood and cerebrospinal fluid (CSF). Only LDH was elevated in CSF and the rest
      were normal. Retinoblastoma gene could not be isolated in this patient. It is
      proposed that LDH in CSF should be analysed in patients with bilateral
      retinoblastoma who had normal brain scan initially. If LDH level in CSF is
      elevated, the patient should be periodically monitored by non-invasive imaging of
      the brain to detect intracranial tumour at an early stage.

PMID- 9663323
TI  - A case of accelerated development of proliferative diabetic retinopathy in a
      woman with type 2 diabetes mellitus after pregnancy.
AB  - Whilst it is recognised that diabetic retinopathy is a consequence of prolonged
      elevation of blood glucose levels, recent studies suggest rapid normalisation of
      blood sugar as a causal factor in accelerating its development. In this case
      report, a non-insulin dependent diabetic with poor blood glucose control but no
      retinopathy in early pregnancy had normalisation of glucose control by the third
      trimester. However, glucose control deteriorated rapidly postnatally, and she had
      a sudden blurring of vision three months after delivery of her baby, at which
      time severe proliferative diabetic retinopathy was diagnosed. The reason for the
      unusually rapid development of proliferative retinopathy was uncertain, but
      appeared to have a temporal association with the deterioration of her glycaemic
      control postnatal after a period of strict diabetes control in the perinatal
      period.

PMID- 9663324
TI  - Traumatic dislocation of the testes.
AB  - Dislocation of the testes is an uncommon sequela of trauma. In contemporary
      times, it is usually associated with motorcycle accidents. We present 2 cases of
      unilateral traumatic testicular dislocation and 1 case of bilateral dislocation,
      all involving motorcyclists. Spontaneous reduction is rare. Early reduction is
      recommended because of histological changes seen in dislocated testes. Surgical
      reduction is often required. The significance of this condition must be
      emphasised to doctors managing trauma patients and early urological consultation
      obtained.

PMID- 9663325
TI  - A case report of a patient with bronchial carcinoid tumour and late presentation
      of Cushing's syndrome.
AB  - Bronchial carcinoid tumour with ectopic adrenocorticotrophin (ACTH) production is
      an uncommon cause of Cushing's syndrome. In most instances, the patient presents
      with clinical hyperglucocorticolism and a search for its underlying pathology
      leads to the discovery of an inconspicuous bronchial carcinoid tumour, if at all.
      Often the tumour is not immediately detectable. We report a patient who presented
      in the reverse order--she initially had a large asymptomatic bronchial carcinoid
      tumour that subsequently manifested as clinical Cushing's syndrome after
      remaining quiescent for four years.

PMID- 9663326
TI  - Subclavian-oesophageal fistula as a complication of foreign body ingestion: a
      case report.
AB  - Foreign bodies in the upper aerodigestive tract are very common. In the local
      community, the commonest foreign body encountered in the oesophagus is the fish
      bone. Impaction in the thoracic oesophagus can lead to perforation and the
      subsequent formation of an arterial-oesophageal fistula. Such fistulae are
      inevitably aorto-oesophageal in nature. A subclavian-oesophageal fistula is
      described in this patient.

PMID- 9663327
TI  - Systemic sclerosis in DRw52-positive silica-exposed males: a case report.
AB  - The aims of this paper were to describe clinical and laboratory details of 4
      siblings, of whom 2 have systemic sclerosis and to describe this family in the
      context of reported cases of familial systemic sclerosis. The proband and his
      affected male sibling share the tissue typing antigens: HLA11, B57, DR13, DRw52,-
      and DQ2,6. Both were concordant for gender, silica exposure, marital status,
      migration history and antinuclear factor status but discordant for systemic
      sclerosis subtype, age at disease onset and ENA status. One non-affected sibling
      had no disease despite concordance for gender, HLA status, silica exposure,
      marital status, and migration history.

PMID- 9663328
TI  - Ergotism and vascular insufficiency: a case report and review of literature.
AB  - We report a case of ergot-induced peripheral vascular insufficiency of the lower
      limbs and review the vascular complications, angiographic findings and the
      different modalities of treatment. The following case report highlights the
      clinical features and course of ergot toxicity, and the difficulty in early
      diagnosis.

PMID- 9663329
TI  - A case series of Paget's disease of bone: diagnosing a rather uncommon condition
      in Singapore.
AB  - Paget's disease of bone is an uncommon condition in the Asian population, with
      only 2 cases reported in medical literature so far. We discuss 5 cases of Paget's
      disease who presented over an 8-year period with a wide and interesting variety
      of clinical features. Though 4 out of the 5 patients were asymptomatic, all of
      them had characteristic radiological features and elevated serum alkaline
      phosphatase levels of varying degrees. Diagnosis was based on the clinical
      features, the elevated serum alkaline phosphatase levels, and most importantly,
      the distinctive radiographic features, which are almost pathognomonic of the
      condition. The incidence of Paget's disease is probably under-reported in Asia
      and Singapore, as it is rarely encountered and can be easily overlooked due to
      its usually asymptomatic and benign nature. A high index of suspicion and an
      active search for its typical features are thus essential for its detection.

PMID- 9663331
TI  - New concepts and theories.

PMID- 9663330
TI  - Urinary 2/16 alpha-hydroxyestrone ratio: correlation with serum insulin-like
      growth factor binding protein-3 and a potential biomarker of breast cancer risk.
AB  - Metabolism of estradiol occurs via two mutually exclusive hydroxylative pathways,
      yielding metabolites of divergent biological properties. 2-hydroxyestrone (2OHE1)
      is anti-estrogenic while 16 alpha-hydroxyestrone (16 alpha OHE1) is a potent
      estrogen. The ratio of 2OHE1 to 16 alpha OHE1 (2/16 alpha-OHE1 ratio) represents
      the net in vivo estrogenic activity. In this study, we sought to determine if the
      urinary 2/16 alpha-OHE1 ratio could be a predictor of breast cancer risk and the
      factors which influence this ratio. Variables analysed included age at diagnosis,
      menopausal status, parity, use of oral contraceptives, body mass index, serum
      levels of insulin-like growth factor-I (IGF-I), IGF binding proteins (BPs) and
      the presence of breast cancer. Serum and urine were collected from 65 breast
      cancer patients and 36 controls after an overnight fast. Urinary estrogen
      metabolites were measured by enzyme immunoassays while serum levels of IGF-I, BP
      1 and BP-3 were determined by immunoradiometric assays. 2OHE1 levels and 2/16
      alpha-OHE1 ratios were significantly lower (P < 0.05) while 16 alpha OHE1 levels
      were higher (P < 0.01) in cancer patients. Multiple linear regression analysis
      showed that levels of urinary metabolites were influenced by parity and breast
      carcinoma. 2/16 alpha-OHE1 ratio correlated positively with serum BP-3 level (P =
      0.03). By multiple logistic regression, 2/16 alpha-OHE1 ratio was the most
      significant factor predictive of breast cancer. The odds ratio for women with
      higher 2/16 alpha-OHE1 ratios was 0.10 (0.03-0.38, 95% confidence interval). In
      conclusion, the profile of urinary estradiol metabolites was distinctly altered
      in breast cancer patients. In addition, BP-3 may be a potential mechanism by
      which estradiol metabolites influence breast cancer progression. As 16 alpha OHE1
      has been shown to initiate neoplastic transformation of mammary epithelial cells,
      the 2/16 alpha-OHE1 ratio may serve as a biomarker of increased risk of breast
      cancer.

PMID- 9663332
TI  - Genetic engineering of glucose-stimulated insulin secretion in Chinese hamster
      ovary cells.
AB  - To engineer an a non-islet cell capable of glucose-stimulated insulin secretion,
      a chinese hamster ovary cell line (CHO) was transfected with a mammalian
      expression vector carrying the human insulin cDNA (pCB/hINS). More proinsulin
      than insulin was released daily by the stably transformed cell line (CHO-INS).
      Examination of acid-ethanol extracts confirmed that both insulin and proinsulin
      were stored. Immunohistochemical analysis of the cells also showed that
      (pro)insulin was stored. Unlike beta cells, CHO-INS cells did not secrete insulin
      in response to glucose. To investigate this lack of effect, we examined whether
      transfection of GLUT2 cDNA, which is ordinarily not expressed in CHO-INS cells,
      would confer glucose-stimulated insulin secretion. Consequently, we have
      demonstrated that glucose regulated insulin release occurs in the CHO-INS-GLUT2
      cell line and that glucose potentiates the insulin secretory response to non
      glucose secretagogues.

PMID- 9663333
TI  - Artificial cell containing superoxide dismutase--selection of folding aids for
      stabilisation of SOD.
AB  - Superoxide dismutase (abbreviated as SOD) has been vigorously studied in the
      fields of radical chemistry and related life science. One of practical problems
      is how to keep its activity in certain adverse conditions causing denaturation.
      Artificial cell containing SOD can be prepared by polymer encapsulation or
      nanocapsulation which has been found to be effective to improve the stability of
      SOD. For construction of an ideal artificial cell system, some folding aids or
      aggregation inhibitors were utilised to enhance SOD stability. In this study,
      three groups of biopolymers are selected as folding aids or aggregation
      inhibitors for stabilisation of SOD, i.e. albumin, carbohydrates and
      glycoproteins. Results indicate that the thermostability of SOD is affected by
      different sort of albumin while some carbohydrates such as cyclodextrins are
      found to be able to enhance SOD stability. In addition, it is firstly found that
      selected glycoproteins such as alpha-macroglobulin and ovalbumin are several
      types of effective folding aids for stabilisation of SOD. They can protect SOD
      against denaturation even at very high temperature(over 100 degrees C). The
      stability was tested by the measurement of SOD activity loss using autooxidation
      method in different adverse conditions such as high temperature, extreme pH
      medium, proteolytic hydrolysis and long shelf life storage. The possible
      stabilisation mechanism of using cyclodextrins and glycoproteins as folding aids
      were discussed.

PMID- 9663334
TI  - Influence of intravenous perfluorocarbon administration on the dynamic behavior
      of lung surfactant.
AB  - Intravenous administration of perfluorocarbon (PFC) compounds can lead to
      pulmonary hyperinflation and respiratory distress in some mammals. This study was
      designed to quantify the effects of two PFC emulsions on the dynamic behavior of
      lung surfactant and to demonstrate that PFC is retained in the liquid lining the
      lung. New Zealand White rabbits received isotonic saline (3 ml/kg), Fluosol (15
      ml/kg) or Oxygent (90% perfluorooctyl-bromide emulsion, 3 ml/kg). After seven
      days we euthanized the animals and lavaged the lungs. Surface tension-surface
      area relationships (sigma-A loops) were measured with the lavage fluid placed in
      a Wilhelmy plate-oscillating bellows apparatus. Loop hysteresis area after
      Fluosol administration was 334 +/- 92 dyne-cm, significantly greater than after
      saline (203 +/- 36 dyne-cm) but not Oxygent (274 +/- 66 dyne-cm). Loop hysteresis
      slope was higher with Oxygent (0.8 +/- 0.4 dyne/cm3) than after saline (0.6 +/-
      0.3 dyne/cm3) or Fluosol (0.5 +/- 0.1 dyne/cm3). 282 MHz 19F NMR spectral
      analysis demonstrates that both PFCs tested appear only in the extracellular
      fraction of the lavage fluid. These results show that pulmonary elimination of
      intravascular PFC leads to PFC presence in the liquid lining the airways where it
      alters surfactant dynamic mechanical behavior.

PMID- 9663335
TI  - Heat-aggregated human IgG as immunosorbent for rheumatoid arthritis.
AB  - In order to selectively remove pathogenic rheumatoid factors (RF) from plasma of
      rheumatoid arthritis (RA) patients, a new immunosorbent was developed by
      immobilizing heat-aggregated human IgG (HAH IgG) on epichlorohydrin-activated
      agar gel. Different parameters influencing ligand coupling were studied, i.e.,
      ligand concentration, reaction time, temperature and pH. The maximum amount of
      HAH IgG immobilized on the carrier was 2.7 mg/ml. Adsorption capacity was
      evaluated by ELISA technique. After incubation of 3.0 ml of RA plasma with 1.0 ml
      of the adsorbent, the RF IgM, IgG, and IgA were removed by 88%, 74%, and 50%,
      respectively. The decrease of total immunoglobulins and albumin were less than 7%
      and 9%. In vitro, perfusion of 10.0 ml plasma at 37 degrees C through 3.0 ml of
      adsorbent, at a flow rate of 5.0 ml/min for 60 min, resulted in the removal of
      49% of RF IgM, 72% of RF IgG and 58% of RF IgA. No leakage of ligand and no
      decline in adsorption capacity and mechanical strength were observed after steam
      sterilization.

PMID- 9663336
TI  - Preparation of red blood cells containing exogenous hemoglobin.
AB  - A technique is described for opening the membrane of a red blood cell by
      electroporation in a manner which permits free exchange of the native hemoglobin
      with exogenous hemoglobin in the surrounding medium. After resealing the RBC's
      demonstrate near normal size and hemoglobin content and retain an effective
      methemoglobin reduction system. This method can be used to introduce natural or
      genetically engineered hemoglobins with altered oxygen binding characteristics.
      Allosteric effectors and other non-diffusible small molecules can be encapsulated
      during the same procedure. A fish Root effect hemoglobin exchanged into rat RBC's
      produced oxygen transport characteristics, unloading at high pressure at acidic
      pH, which should be useful to treat tissue hypoxia from a variety of causes.

PMID- 9663337
TI  - An engineering model to characterize oxygen transfer rates for liposome
      encapsulated hemoglobin (LEH).
AB  - An engineering model was designed to evaluate oxygen transfer rates for LEH and
      other oxygen carriers under wall shear rates from 150 sec-1 to 450 sec-1. The
      results showed that increasing the shear rates (or flow rates) of oxygen carriers
      flowed inside of hollow fiber tubes would increase oxygen transfer rates to
      outside media. The values of overall oxygen transfer rate coefficients for LEH,
      based on 1 g/dl of hemoglobin contents, were about 2 to 2.5 times higher than
      those values for human blood at all of tested shear rates (e.g., 5.1 x 10(-5)
      cm/sec and 2.1 x 10(-5) cm/sec for LEH and blood at wall shear rates of 450 sec
      1, respectively). Moreover, the results of oxygen transfer efficiency for LEH
      calculated by this model were consistent with the similar results reported by
      Usuba et al.[3] obtained by animal study. With an engineering model, we possibly
      estimate the effects of other factors such as viscosity on the oxygen transfer
      rates for LEH in microcirculation.

PMID- 9663338
TI  - Immobilization of microalgae for biosorption and degradation of butyltin
      chlorides.
AB  - Since the discovery of their biocidal properties in the 1950s, organotin
      compounds have found a large spectrum of industrial applications such as wood and
      textile preservatives, fungicides and pesticides, and antifouling paint on ships
      and fishing equipment. The fate and environmental impact of butyltins have been
      the subjects of a large body of research in the last decades. Biosorption and
      degradation of butyltin compounds by immobilized microalgae chlorella were
      studied in this paper, aiming to find an alternative way to solve organotin
      pollution problem. Chlorella emersonii cells were entrapped in a calcium aginate
      matrix. The cell growth rates, respiratory rate and chlorophyll a content were
      studied and compared. Results showed that immobilized chlorella had increased
      respiratory and growth rates, and almost equal chlorophyll a content when
      compared with free cells. Cell leakage was slight during the 20-day experimental
      period Cell leakage from the matrix was unrelated to cell growth within the
      matrix. Immobilized chlorella was applied to deal with butytin contaminated
      aquatic solutions. Immobilized chlorella had increased degradation rates of tri-,
      di-, and mono-butyltin chlorides in aquatic solutions, and lower biological
      accumulation factors on cells, than free cells, which indicates a potential use
      for tackleing organotin polluted water body.

PMID- 9663339
TI  - Exploratory design in medical nanotechnology: a mechanical artificial red cell.
AB  - Molecular manufacturing promises precise control of matter at the atomic and
      molecular level, allowing the construction of micron-scale machines comprised of
      nanometer-scale components. Medical nanomachines will be among the earliest
      applications. The artificial red blood cell or "respirocyte" proposed here is a
      bloodborne spherical 1-micron diamondoid 1000-atm pressure vessel with active
      pumping powered by endogenous serum glucose, able to deliver 236 times more
      oxygen to the tissues per unit volume than natural red cells and to manage
      carbonic acidity. An onboard nanocomputer and numerous chemical and pressure
      sensors enable complex device behaviors remotely reprogrammable by the physician
      via externally applied acoustic signals.

PMID- 9663340
TI  - Preparation and blood compatibility of new silica-chitosan hybrid biomaterials.
AB  - The development of new materials containing both organic and inorganic structures
      is of great interest with respect to achievement of obtaining the special
      properties, and the solgel process has provided new opportunities for making such
      materials. In this paper, new silica-chitosan hybrid biomaterials were produced
      by this technique, using biopolymer chitosan and its heparin-like derivative as
      the organic species to be incorporated into the silicon alkoxide (TEOS) based
      network. All the samples made were in form of thin, flexible films with optical
      clarity. Microphase separated structure was observed in the hybrid surface, with
      hydrophobic SiO2 and hydrophilic chitosan interleaved. These hybrid materials
      displayed good blood compatibility in comparison with their single component
      systems.

PMID- 9663341
TI  - In vitro experimental research of rabbit condrocytes biostimulation with diode
      laser Ga-Al-As: a preliminary study.
AB  - The scope of our study was to verify the effects of a new diode laser device with
      active material composed of Gallium, Aluminum and Arsenic (Ga-Al-As) configured
      as MOCVD (780 nm., 3000 mW) for the biostimulation of the cartilage cells in
      vitro. The condrocytes cells, withdrawn from the cartilage of the medial condyle
      of the femur of the rabbit, were cultivated, incubated and subject to
      biostimulation treatment with the laser. The condrocytes cells were placed in 24
      Petri dishes at the concentration of 0.25 x 10(5)/ml and divided into 4 groups: 3
      group (I, II, III) were treated with the laser and the fourth group (IV) was used
      as the control group. At the end of the treatment, all four groups, were
      evaluated with a MTT test and a cell count of the condrocytes cells. Group III
      (300 J, 1 Watt, 300 Hz, 10' of exposure time with a pulsating emission) provided
      the best results in terms of cell viability (MTT test) and for the number of
      cells found in the dishes when compared to the other treated groups and the
      control group. The results obtained with the use of this new diode laser Ga-Al-As
      device in the biostimulation of the cartilage tissue, permits us to consider the
      use of this device clinically.

PMID- 9663342
TI  - Putting universal healthcare on the religious agenda.

PMID- 9663343
TI  - Health reform in America: the mystery of the missing moral momentum.

PMID- 9663344
TI  - A Protestant perspective on access to healthcare.

PMID- 9663345
TI  - A Catholic perspective on access to healthcare.

PMID- 9663347
TI  - Unheard voices: religious perspectives on access to healthcare. CQ
      sources/bibliography.

PMID- 9663346
TI  - A Jewish perspective on access to healthcare.

PMID- 9663348
TI  - Bringing clarity to the futility debate: don't use the wrong cases.

PMID- 9663349
TI  - Cloning and infertility.

PMID- 9663350
TI  - Alzheimer testing at Silver Years.

PMID- 9663351
TI  - Paradigms for clinical ethics consultation practice.

PMID- 9663352
TI  - Some narrative methodologies for clinical ethics.

PMID- 9663353
TI  - Response to "This porridge is too thin" by Gretchen M. Brown and "Demolishing a
      'straw man'" by Elliott J. Rosen (CQ Vol 7, no 2).

PMID- 9663354
TI  - The greening of bioethics: corporate funding of bioethics research.

PMID- 9663355
TI  - The impact of nonsteroidal anti-inflammatory drugs on hypertension: alternative
      analgesics for patients at risk.
AB  - An estimated 25% of the overall population of the United States and 55% to 60% of
      the population aged 65 to 74 years are hypertensive. Many patients with
      hypertension, particularly elderly patients, also take nonsteroidal anti
      inflammatory drugs (NSAIDs), the most commonly prescribed analgesic medications
      in the United States. It is estimated that as many as 20 million patients and 12%
      of the population aged > or = 60 years are taking concurrent NSAIDs and
      antihypertensive medication. This overlap is significant, because NSAIDs inhibit
      eicosanoid synthesis and can thus limit the effectiveness of antihypertensive
      drugs that exert all or part of their blood-pressure-lowering action through the
      stimulation of eicosanoid synthesis or release. Overviews of clinical trial data
      indicate that the blood pressure of patients with controlled hypertension can be
      raised by 3 to 6 mm Hg during concurrent treatment with NSAIDs, which can produce
      a significant increase in subsequent stroke, end-stage renal disease, or
      congestive heart failure. The incidence of these sequelae increases with age.
      Clinicians should have greater awareness of the potential impact of NSAIDs on
      blood pressure control, especially in high-risk patients such as the elderly and
      those with chronic pain or uncontrolled hypertension. Unless an NSAID is deemed
      absolutely necessary, the clinician should consider alternative analgesics that
      do not affect prostaglandin synthesis. These include acetaminophen, tramadol,
      and, in some cases, narcotic analgesics.

PMID- 9663356
TI  - Efficacy of interferon monotherapy in the treatment of relapsers and
      nonresponders with chronic hepatitis C infection.
AB  - Results of numerous studies have demonstrated similar efficacy profiles for the
      interferons (IFNs) currently approved for the treatment of chronic hepatitis C
      virus (HCV) infection. Although it has been suggested that some IFNs are more
      efficacious in certain patient populations, the current data support an
      equivalent efficacy and safety profile for these agents. Among patients requiring
      retreatment, no single study has made a direct comparison of IFN alfa-2b (IFN
      alpha 2b) and consensus IFN (CIFN) in patients who have relapsed or have not
      responded to previous IFN therapy. However, at least 11 studies using IFN-alpha
      2b and 1 using CIFN have demonstrated efficacy in the relapsing and nonresponding
      patient populations. A review of these studies suggests that overall efficacy and
      tolerability are similar regardless of IFN-alpha subtype. Overall, up to 59% and
      83% of relapsed patients retreated with IFN have shown sustained response rates,
      as measured by negative HCV RNA titer and normalization of alanine
      aminotransferase (ALT) levels, respectively. Up to 14% and 25% of patients who
      failed to respond to previous IFN therapy have shown sustained HCV RNA response
      and normalization of ALT, respectively, after retreatment.

PMID- 9663357
TI  - An elective-titration study of the comparative effectiveness of two angiotensin
      II-receptor blockers, irbesartan and losartan. Irbesartan/Losartan Study
      Investigators.
AB  - This multicenter, randomized, double-masked, elective-titration study was
      designed to compare the effectiveness, safety, and tolerability of irbesartan and
      losartan, two angiotensin II subtype AT1-receptor blockers, in the treatment of
      patients with mild-to-moderate hypertension. After a 3-week, single-masked,
      placebo lead-in period, 432 patients with a mean seated diastolic blood pressure
      (SeDBP) of 95 to 115 mm Hg were randomly allocated to receive either irbesartan
      150 mg once daily (n = 213) or losartan 50 mg once daily (n = 219). At week 4, if
      SeDBP at trough (i.e., 24 +/- 3 hours after the previous dose) was > or = 90 mm
      Hg, the daily dose was doubled (to irbesartan 300 mg or losartan 100 mg). At week
      8, if trough SeDBP was > or = 90 mm Hg, hydrochlorothiazide 12.5 mg once daily
      was added to the regimen; consistent with the prescribing information for
      losartan, the dose of losartan was reduced to 50 mg once daily on the addition of
      hydrochlorothiazide. A total of 370 patients (178 irbesartan and 192 losartan)
      were evaluable for efficacy. The mean change in trough SeDBP at week 8, the
      primary efficacy end point, was significantly greater in patients receiving
      irbesartan monotherapy than in those receiving losartan monotherapy (-10.2 mm Hg
      vs -7.9 mm Hg, respectively). At week 12, reductions in trough SeDBP and seated
      systolic blood pressure were greater with irbesartan treatment than with losartan
      treatment (-13.8 mm Hg vs -10.8 mm Hg and -18.0 mm Hg vs -13.9 mm Hg,
      respectively), and a greater proportion of irbesartan patients responded to
      therapy (i.e., trough SeDBP < 90 mm Hg or reduction in trough SeDBP > or = 10 mm
      Hg) compared with losartan patients (78% vs 64%, respectively). Both regimens
      were well tolerated.

PMID- 9663358
TI  - Viscosupplementation with hylan G-F 20: a 26-week controlled trial of efficacy
      and safety in the osteoarthritic knee.
AB  - Hylan G-F 20, which is derived from hyaluronan, is a highly purified,
      elastoviscous fluid with rheologic properties similar to those of synovial fluid
      in the knee joints of healthy young persons. The efficacy and safety of
      viscosupplementation with hylan G-F 20 were evaluated in a multicenter, double
      masked clinical study in patients with chronic idiopathic osteoarthritis (OA) of
      the knee of 1 to 30 years' duration. Three intra-articular injections of 2 mL
      hylan G-F 20 were administered 1 week apart to 57 knees. The control group (60
      knees) received 2 mL of physiologic buffered saline solution at the same
      intervals. Patients were predominantly female (65%), with a mean age of 62 years
      and mean weight of 76 kg. Using a visual analogue scale, patients assessed the
      following clinical variables: pain during weight-bearing, pain at rest during the
      night, reduction of pain during the most painful movement of the knee, and
      treatment success. Evaluators also assessed patients' loss of activity while
      performing difficult daily tasks and treatment success. There was dramatic early
      improvement in all six variables with hylan G-F 20 beginning after the first
      injection; the improvement continued through the study end points. The
      differences between hylan G-F 20 and saline treatment were statistically
      significant for all outcome measures. In the hylan G-F 20 group, 39% to 56% of
      patients were free or nearly free of weight-bearing pain 10 to 24 weeks after the
      last injection. Treatment with saline was less effective, with fewer than 13% of
      patients free or nearly free of weight-bearing pain. Use of rescue therapy was
      significantly greater in the saline group than in the hylan G-F 20 group. No
      adverse events were observed in the injected joint after hylan G-F 20 treatment.
      These results demonstrate that hylan G-F 20 is effective and well tolerated in
      the management of chronic idiopathic OA.

PMID- 9663359
TI  - Fluticasone propionate 50 micrograms BID versus 100 micrograms BID in the
      treatment of children with persistent asthma. Fluticasone Propionate Study Group.
AB  - The aim of this multicenter, double-masked study was to compare the efficacy and
      safety of two different doses of inhaled fluticasone propionate dry powder--50
      micrograms and 100 micrograms--administered BID via a multidose powder inhaler
      with those of placebo in the treatment of children with persistent asthma. After
      a 2-week run-in period, 263 patients were randomized to treatment with twice
      daily placebo (n = 92), fluticasone 50 micrograms (n = 85), or fluticasone 100
      micrograms (n = 86) for 12 weeks. One hundred sixty-six (63%) patients were male,
      and 224 (85%) were white, with a mean age of 8 years. Two hundred twenty-one
      (84%) patients were atopic, and 167 (63%) had been asthmatic for 1 to 5 years.
      Baseline mean morning peak expiratory flow (PEF) values were 207 L/min, 199
      L/min, and 194 L/min, and baseline percentages of predicted normal values were
      86%, 80%, and 81% for the groups receiving placebo, fluticasone 50 micrograms,
      and fluticasone 100 micrograms, respectively. At the end of the first week of
      treatment, patients in both fluticasone groups had significantly greater
      improvements in morning PEF than did those receiving placebo. Patients
      experienced mean increases of 4 L/min, 22 L/min, and 26 L/min with placebo,
      fluticasone 50 micrograms, and fluticasone 100 micrograms, respectively. At the
      end point (the last evaluable visit), patients in both fluticasone groups
      continued to have significantly greater improvements in morning PEF than did
      patients receiving placebo. Patients experienced mean increases of 17 L/min, 50
      L/min, and 57 L/min with placebo, fluticasone 50 micrograms, and fluticasone 100
      micrograms, respectively. Changes in the percentage of predicted values by end
      point were 8%, 20%, and 26% with placebo, fluticasone 50 micrograms, and
      fluticasone 100 micrograms, respectively. The probability of remaining in the
      study, according to predefined withdrawal criteria, indicated a significant
      treatment difference in favor of fluticasone. Withdrawal criteria were met by
      63%, 42%, and 29% of patients receiving placebo, fluticasone 50 micrograms, and
      fluticasone 100 micrograms, respectively. This study clearly demonstrates the
      superiority of fluticasone 50 and 100 micrograms BID over placebo in the
      treatment of persistent asthma in children.

PMID- 9663360
TI  - Domperidone in the management of symptoms of diabetic gastroparesis: efficacy,
      tolerability, and quality-of-life outcomes in a multicenter controlled trial. DOM
      USA-5 Study Group.
AB  - The purpose of this clinical study was to determine the efficacy, tolerability,
      and impact on quality of life of domperidone--a specific peripherally acting
      dopamine antagonist--in the management of symptoms of gastroparesis, a common and
      potentially debilitating condition in patients with diabetes mellitus. In the
      first phase of this multicenter, two-phase withdrawal study, 287 diabetic
      patients with symptoms of gastroparesis of at least 6 months' duration received
      domperidone 20 mg QID in a single-masked fashion for 4 weeks. Efficacy was
      evaluated using a four-point rating scale (0 = none, 1 = mild, 2 = moderate, 3 =
      severe) for each of the following symptoms: nausea, abdominal
      distention/bloating, early satiety, vomiting, and abdominal pain. At the end of
      the first phase, patients with sufficient improvement in their total symptom
      score (a score < or = 6 and a decrease in score of > or = 5 units from the
      baseline [selection] visit) were eligible for the 4-week, randomized, placebo
      controlled, double-masked withdrawal phase of the study. The impact of
      domperidone on quality of life was determined using the Medical Outcomes Study
      Short Form-36 (SF-36). Of 269 patients with data from the single-masked phase,
      208 (77%) qualified for entry into the double-masked phase based on a
      statistically significant improvement in total symptom score, from a mean score
      of 10.32 at baseline (initial visit) to 3.79 after 4 weeks of single-masked
      domperidone therapy. During the double-masked phase, patients in the placebo
      group had significantly greater deterioration in total symptom scores compared
      with patients in the domperidone group (mean changes of 1.84 and 0.85,
      respectively). Similar significant differences in favor of domperidone were seen
      in the secondary efficacy variables (i.e., patients' diary scores and global
      assessments of symptoms). The tolerability profile of domperidone was similar to
      that of placebo. Patients who responded to domperidone experienced significant
      improvements in quality of life, as indicated by the SF-36 physical and mental
      component summary scores. During the double-masked phase, patients who were
      randomized to placebo experienced a significant deterioration in the physical
      component summary score compared with patients in the domperidone group. The
      results of this study suggest that domperidone 20 mg QID provides significant
      improvement in the upper gastrointestinal symptoms of diabetic gastroparesis and
      is well tolerated in patients with this condition.

PMID- 9663361
TI  - Comparison of the efficacy and safety of 2% dorzolamide and 0.5% betaxolol in the
      treatment of elevated intraocular pressure. Dorzolamide Comparison Study Group.
AB  - A multicenter, parallel-design, randomized, double-masked study was conducted to
      compare the efficacy and safety of 2% dorzolamide with those of 0.5% betaxolol in
      the treatment of elevated intraocular pressure (i.o.p). A total of 311 adults
      with ocular hypertension or open-angle glaucoma were randomly allocated to
      receive either 2% dorzolamide administered topically TID or 0.5% betaxolol
      administered topically BID plus placebo administered topically QD for 12 weeks.
      After the washout of previous ocular hypotensive drugs, patients with IOP > or =
      23 mm Hg in at least one eye at 10 AM or 4 PM on study day 1 were randomly
      allocated to receive one of the study treatments. Throughout the study, IOP was
      measured 2 and 8 hours after instillation of study medication for the morning
      peak effect (hour 2) and afternoon trough effect (hour 8). After 12 weeks of
      therapy, the mean change in IOP was not significantly different between the
      dorzolamide and betaxolol treatment groups at hour 8 (-3.6 mm Hg in both groups)
      or hour 2 (-5.4 vs -5.3 mm Hg, respectively). The differences between treatments
      (and 95% CIs associated with these differences) in mean IOP changes from baseline
      were 0.02 mm Hg (-0.870 to 0.901) for hour 8 and -0.14 mm Hg (-0.959 to 0.685)
      for hour 2. The ocular adverse experience (AE) most frequently reported by
      patients was ocular burning and/or stinging, and the most frequently reported
      nonocular AEs were taste perversion, upper respiratory infection, and headache.
      Only the incidence of taste perversion was significantly different between
      treatment groups (14.6% for the dorzolamide group and 0.0% for the betaxolol
      group). Two percent of patients in each treatment group discontinued the study
      due to AEs. This study confirmed the similar IOP-lowering effect of 2%
      dorzolamide and 0.5% betaxolol. Both treatments were generally well tolerated,
      and their safety profiles were similar.

PMID- 9663362
TI  - A randomized, open-label comparison of venlafaxine and fluoxetine in depressed
      outpatients.
AB  - In this randomized, open-label, 8-week comparative study, the efficacy and safety
      of venlafaxine and fluoxetine were assessed in outpatients with major depression.
      One hundred forty-five patients were assigned to receive venlafaxine 37.5 mg
      twice daily or fluoxetine 20 mg once daily. On day 15, if clinically indicated to
      improve patient response, the dosage could be increased at the investigator's
      discretion to venlafaxine 75 mg twice daily or fluoxetine 40 mg once daily. One
      hundred forty-five patients were evaluated for safety and 110, for efficacy. The
      mean age was 37 years, and 70% of the patients were female. In both treatment
      groups, mean scores on the Hamilton Depression Rating Scale decreased
      significantly between baseline (27.8, venlafaxine; 29.2, fluoxetine) and the end
      of the study (8.7, venlafaxine; 8.2, fluoxetine). Similarly, mean scores on the
      Montgomery-Asberg Depression Rating Scale decreased significantly between
      baseline (31.4, venlafaxine; 31.6, fluoxetine) and the end of the study (8.3,
      venlafaxine; 7.6, fluoxetine). In venlafaxine patients, the most common adverse
      events were nausea (44.3%), headache (40.0%), insomnia (31.4%), dizziness
      (30.0%), and dry mouth (22.9%); in fluoxetine patients, they were headache
      (32.0%), nausea (28.0%), insomnia (24.0%), anxiety (21.3%), sleepiness (20.0%),
      and generalized tremor (20.0%). The results of this study indicate that
      venlafaxine is effective and well tolerated for the treatment of major depression
      at doses of 37.5 or 75 mg twice daily and not significantly different from
      fluoxetine 20 or 40 mg once daily.

PMID- 9663363
TI  - Effects of cerivastatin sodium, a new HMG-CoA reductase inhibitor, on biliary
      lipid metabolism in patients with hypercholesterolemia.
AB  - The use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors
      has become common in the treatment of hypercholesterolemia. The present
      uncontrolled study was undertaken to determine the effect of cerivastatin sodium
      (BAY w 6228), a new HMG-CoA reductase inhibitor, on biliary lipid levels in
      patients with hypercholesterolemia. Twenty-one hypercholesterolemic patients
      (World Health Organization type IIa = 16 patients; type IIb = 5 patients)
      received placebo during a 4- to 6-week observation period, after which they
      received cerivastatin sodium 0.2 mg/d for 12 weeks. Fasting blood samples were
      drawn for the measurement of serum lipid levels early in the morning before the
      start of treatment and once a month for each of the 12 weeks of cerivastatin
      sodium treatment. Gallbladder bile samples were aspirated with a duodenal tube by
      cerulein stimulation to assess bile lithogenicity. Serum total cholesterol levels
      decreased markedly after 12 weeks. However, no significant difference was found
      in the molar percentage composition of biliary lipids (e.g., cholesterol,
      phospholipids, and total bile acids) or in individual biliary bile acids.
      Consequently, no significant change in bile cholesterol saturation index was
      found. The index values before and after 12 weeks of treatment were 0.81 +/- 0.38
      and 0.80 +/- 0.47, respectively, whereas when patients were grouped by type of
      hypercholesterolemia, there was a tendency toward decreased lithogenicity in
      patients with type IIb but not type IIa hypercholesterolemia. We concluded that
      cerivastatin sodium was an effective cholesterol-lowering drug that did not
      appear to worsen biliary lipid metabolism and that may decrease lithogenicity in
      patients with type IIb hypercholesterolemia.

PMID- 9663364
TI  - Assessment by patients with diabetes mellitus of two insulin pen delivery systems
      versus a vial and syringe.
AB  - Two multicenter surveys were conducted in a total of 1310 insulin users over a 3
      week period. The first survey, in which 803 patients participated, assessed the
      effects of using the Novolin Prefilled insulin delivery system on lifestyle;
      compliance with insulin, diet, and exercise regimens; and feelings of well-being
      compared with the traditional insulin vial and syringe. The second survey, in
      which 507 patients participated, assessed attitudes and perceptions of the
      NovoPen 1.5 insulin delivery system compared with the traditional insulin vial
      and syringe. Both delivery systems are dial-a-dose insulin pens containing a
      single-use NovoFine 30 insulin needle and are designed to be portable and
      discreet. Patients using the Novolin Prefilled delivery system completed a three
      part questionnaire (two parts at the initial survey visit and the third at the
      end of 3 weeks); those using the NovoPen 1.5 completed a questionnaire at the end
      of 3 weeks. Seven hundred twenty-nine (92%) of 793 patients in the Novolin
      Prefilled group and 482 (98%) of 492 patients in the NovoPen 1.5 group reported
      that it was easy to use these delivery systems; 672 (85%) of 791 patients
      reported that they missed no injections while using the Novolin Prefilled system,
      compared with 566 (72%) of 789 patients using the vial and syringe. With the
      NovoPen 1.5, 333 (73%) of 456 patients said that the dosing mechanism was more
      accurate, and 351 (77%) of 456 patients found it easier to comply with their
      insulin regimen. In both groups, patients reported a strong desire to continue
      using the insulin pens and a willingness to recommend their use to someone else.
      Because patients were more physically and psychologically comfortable injecting
      insulin with the Novolin Prefilled or NovoPen 1.5 system than with an insulin
      syringe, their overall attitude toward insulin therapy improved, as did their
      confidence about managing their disease. An improved attitude toward insulin
      therapy might be expected to lead to better acceptance of and compliance with an
      insulin regimen.

PMID- 9663365
TI  - Effects of beano on the tolerability and pharmacodynamics of acarbose.
AB  - Acarbose is an alpha-glucosidase inhibitor approved for the treatment of type 2
      diabetes mellitus. Acarbose inhibits carbohydrate digestion, allowing an
      excessive amount of undigested carbohydrate to reach the colon. Bacterial
      fermentation of the carbohydrate produces intestinal gas, which can cause
      flatulence and abdominal pain. Beano, an over-the-counter enzyme preparation
      (alpha-galactosidase), diminishes intestinal gas production by enhancing the
      breakdown of certain carbohydrates before they reach the lower intestine. This
      study was undertaken to investigate whether concomitant administration of Beano
      and acarbose could reduce the flatulence associated with acarbose and, if so,
      whether Beano would interfere with the effects of acarbose on postprandial serum
      glucose concentration. In this randomized, double-masked, placebo-controlled,
      three-period crossover study, 37 patients with type 2 diabetes mellitus received
      acarbose 100 mg, acarbose 100 mg plus Beano, or placebo. The study population
      consisted of 20 males and 17 females who ranged in age from 36 to 72 years (mean,
      56 years) and in weight from 62 to 142 kg (mean, 92 kg). Each treatment period
      consisted of 3 days, during which both acarbose and Beano were given at the
      beginning of each of three meals. There was a 4-day washout interval between each
      treatment period. The frequency and severity of flatulence were measured using a
      score compiled from patient diaries. As an additional measure of intestinal gas
      production, breath hydrogen concentration was measured on day 3 of each treatment
      period. Postprandial serum glucose concentration was measured at predetermined
      times after each morning dose to assess pharmacodynamic activity. Patients who
      took Beano with acarbose had a significantly lower flatulence score than did
      those who took acarbose alone (0.79 vs 1.09). Consistent with this finding,
      breath hydrogen concentration was lower after administration of acarbose plus
      Beano than with acarbose alone (31.2 ppm vs 50.5 ppm). Beano had variable effects
      on the ability of acarbose to reduce the postprandial serum glucose
      concentration. Although postprandial serum glucose levels were higher in patients
      who received acarbose plus Beano than in those who received acarbose alone, both
      treatments (with or without Beano) resulted in postprandial serum glucose levels
      that were significantly lower than those seen with placebo. Therefore, although
      Beano appeared to diminish the activity of acarbose, postprandial serum glucose
      concentrations still decreased significantly in patients taking Beano with
      acarbose. Beano has been shown to alleviate the flatulence accompanying acarbose
      treatment, but it may also interfere with the glucose-lowering effect of
      acarbose.

PMID- 9663366
TI  - A multicenter evaluation of the efficacy and safety of 150 and 300 mg/d sustained
      release bupropion tablets versus placebo in depressed outpatients.
AB  - This multicenter, randomized, double-masked, placebo-controlled, parallel-group
      study compared the antidepressant efficacy and safety of bupropion sustained
      release (SR) tablets (150 mg QD or 150 mg BID) with placebo in outpatients with
      moderate-to-severe depression. The study consisted of a 1-week placebo phase
      followed by 8 weeks of active treatment with bupropion SR 150 mg/d (150 mg QD, n
      = 121) or 300 mg/d (150 mg BID, n = 120) or placebo (n = 121). Efficacy was
      measured by changes in scores on the 17-item Hamilton Rating Scale for Depression
      (HAM-D) and the Clinical Global Impressions for Severity of Illness (CGI-S) and
      Clinical Global Impressions for Improvement of Illness (CGI-I) scales. Safety was
      monitored by regular assessment of vital signs and adverse events as well as by
      pretreatment and posttreatment physical and clinical laboratory examinations. By
      day 56, both bupropion SR treatments were more effective in relieving the
      symptoms of depression than was placebo. Compared with those receiving placebo,
      patients in the bupropion SR 150- and 300-mg/d groups had significantly reduced
      symptoms by treatment day 56, as measured on the 17-item HAM-D, CGI-S, and CGI-I
      scales (P < 0.05). Bupropion SR was well tolerated, with no serious adverse
      events reported by bupropion-treated patients; 95% of all reported adverse events
      were of mild or moderate intensity. No clinically significant changes in vital
      signs, laboratory test results, or physical findings were observed. A greater
      mean weight loss was observed at the end of treatment in both the bupropion SR
      150-mg (0.5 kg) and bupropion SR 300-mg (1.0 kg) group compared with placebo (0.2
      kg). We found that bupropion SR 150 mg administered either once or twice daily
      was more effective than placebo in treating depression and that once-daily dosing
      appears to be at least as effective as twice-daily dosing. Should this prove
      true, depressed patients may be able to benefit from the convenience and improved
      tolerability associated with once-daily dosing.

PMID- 9663367
TI  - Early onset of antidepressant action of venlafaxine: pattern analysis in intent
      to-treat patients.
AB  - Pattern analysis has been used to distinguish between the true effect of an
      antidepressant and a placebo effect. The placebo effect constitutes clinical
      improvement that is attributable to the caregiver, treatment setting, or placebo
      substance. Pattern analysis allows identification of patients who have early
      persistent responses, delayed persistent responses, or no responses to a drug. In
      our study, we used this method to assess the onset and persistence of
      antidepressant activity of high daily doses of venlafaxine. Our analysis
      considered scores on the Global Improvement item of the Clinical Global
      Impressions scale for intent-to-treat patients in two double-masked, placebo
      controlled studies of at least 6 weeks' duration. Dosages in both studies were
      rapidly titrated upward so patients received at least 200 mg/d within the first
      week of treatment. Improvement within the first 2 weeks was considered early, and
      improvement not followed by a relapse through the scheduled end of treatment was
      considered persistent. Significantly greater percentages of patients in the
      venlafaxine group (27% and 20% in study 1 and study 2, respectively) than in the
      placebo group (9% and 2%, respectively) had a clinically meaningful drug response
      within the first 2 weeks of treatment. This early response persisted for the
      duration of each trial. We concluded that venlafaxine in dosages of at least 200
      mg/d demonstrates an early and persistent onset of efficacy compared with
      placebo.

PMID- 9663368
TI  - Long-term efficacy, tolerability, and safety of the combination of enalapril and
      felodipine ER in the treatment of hypertension. Enalapril-Felodipine ER Factorial
      Study Group.
AB  - A recent 8-week, double-masked, placebo-controlled, 3 x 4 factorial-design study
      demonstrated that enalapril-felodipine extended-release (ER) combinations had
      statistically significant additive effects for reducing both sitting systolic
      blood pressure (SiSBP) and sitting diastolic blood pressure (SiDBP) and were
      generally well tolerated in hypertensive patients with SiDBPs ranging from 95 to
      115 mm Hg. The present open-label study was undertaken to assess the long-term
      efficacy, tolerability, and safety of such combinations. Patients from the
      factorial study were eligible for the 1-year, open-label extension. Initially,
      all patients received enalapril 5 mg-felodipine ER 2.5 mg once daily; if SiDBP
      was not controlled (< 90 mm Hg) after 4 weeks of treatment, the dose was titrated
      upward at 2- to 4-week intervals to a maximum of enalapril 10 mg-felodipine ER 10
      mg. Hydrochlorothiazide (HCTZ) 12.5 mg was added to the regimen of patients whose
      hypertension was not controlled at the highest enalapril-felodipine ER dose. A
      total of 507 patients were enrolled, of whom 502 were assessable. At their last
      study visit, 391 (78%) of the assessable patients were receiving only an
      enalapril-felodipine ER combination. The enalapril-felodipine ER combinations
      resulted in mean trough SiDBPs of 85 to 89 mm Hg (decreases of 13 to 16 mm Hg
      from baseline) and SiSBPs of 137 to 140 mm Hg (decreases of 13 to 21 mm Hg).
      Overall, 407 (81%) of the 502 assessable patients achieved an SiDBP < 90 mm Hg or
      a reduction from baseline > or = 10 mm Hg (responders); such a response was
      recorded in 331 patients (66%) taking a combination of enalapril-felodipine ER
      alone and 76 patients (15%) taking the combination with the addition of HCTZ 12.5
      mg. Blood pressure reductions were maintained throughout the treatment period.
      Drug-related adverse events were relatively infrequent, often transient, usually
      mild, and apparently not dose related. The most frequently reported drug-related
      adverse events were edema/swelling, asthenia/fatigue, dizziness, cough, and
      headache. These results suggest that combination therapy with enalapril
      felodipine ER is effective for long-term blood pressure reduction, has an
      excellent safety profile, and is generally well tolerated. Addition of low-dose
      HCTZ to the enalapril-felodipine ER combination appears to provide further blood
      pressure control without increasing drug-related adverse events.

PMID- 9663370
TI  - Economic impact of introducing propentofylline for the treatment of dementia in
      Sweden.
AB  - The purpose of this study was to estimate the impact of the introduction of
      propentofylline, a glial-cell modulator with neuroprotective properties, on the
      costs of dementia care in Sweden. To estimate the clinical effects of
      propentofylline treatment on dementia, we conducted a meta-analysis of four
      double-masked, placebo-controlled, randomized clinical trials and a simulation in
      a cohort of 57,000 patients with Alzheimer's disease (AD) or vascular dementia
      (VaD). This cohort represented the fraction of the total AD and VaD population in
      Sweden with mild-to-moderate disease, the target population for propentofylline
      treatment. The rate of progression of dementia was expressed in terms of the
      annual rate of change in score on the Mini-Mental State Examination (MMSE). The
      costs of care were estimated on the basis of a prospective population-based
      study. A regression model was used to quantify the costs of dementia care as a
      function of MMSE score. The estimates obtained were used to calculate and compare
      the costs of dementia care until death, with or without propentofylline
      treatment. The sensitivity of the results to a variety of model assumptions was
      also assessed. The total gross cost for 9 years under the current treatment
      strategy was SEK (Swedish kronor) 168.06 billion. Including propentofylline in
      the treatment strategy yielded net savings of SEK 0.8 billion, since the savings
      in the cost of patient care outweighed the drug acquisition costs. Over 9 years,
      this saving represents 3.8% of the costs of dementia care in the target
      population (MMSE score, 15-25 points) and 0.5% of the costs in the total AD and
      VaD population. The annual savings per patient ranged from SEK 5517 to 6387
      during the first 4 years of propentofylline treatment. If an extended
      neuroprotective effect of propentofylline is assumed, savings increase to SEK 1.6
      billion, equivalent to 7.6% of total care costs in the target population and 1.0%
      in the total population. Savings increase to SEK 14.6 billion if the extended
      neuro-protective effect is assumed to be effective in an extended target
      population (MMSE score, 0-25 points) without increased survival. In the
      sensitivity analysis, most scenarios yielded benefits in favor of propentofylline
      treatment. The clinical effects of propentofylline translate into meaningful
      economic effects. The drug acquisition costs are more than offset by the savings
      achieved in the cost of care. The inclusion of a broader range of outcomes may
      increase these savings.

PMID- 9663369
TI  - A long-term comparative trial of cerivastatin sodium, a new HMG-CoA reductase
      inhibitor, in patients with primary hypercholesterolemia.
AB  - Cerivastatin sodium, a synthetic and pure enantiomeric 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase inhibitor, is considered effective in the
      treatment of mild-to-moderate primary hyper-cholesterolemia (total cholesterol <
      or = 220-259 mg/dL) at a daily dose of 0.15 mg. We compared the efficacy and
      tolerability of a dosage of 0.3 mg/d with those of a dosage of 0.15 mg/d in
      patients with severe primary hypercholesterolemia (serum total cholesterol > or =
      260 mg/dL). After a minimum of 4 weeks' lead-in with placebo, 73 patients with
      severe primary hypercholesterolemia were randomly assigned to receive either 0.15
      or 0.3 mg of cerivastatin sodium once daily after the evening meal for 12 weeks.
      In 58 patients, the same drug was continued at a flexible dosage for an
      additional 36 weeks or longer to assess the long-term efficacy and tolerability
      of cerivastatin sodium. During the 12-week treatment period, serum total
      cholesterol levels decreased significantly from baseline in both dosage groups,
      but the percentage reduction was significantly greater in the 0.3-mg group
      (range, 24.4% to 25.6%) than in the 0.15-mg group (range, 19.4% to 21.6%). The
      percentage reduction in levels of low-density lipoprotein cholesterol,
      triglycerides, and apolipoprotein B and the percentage increase in levels of high
      density lipoprotein cholesterol were significantly greater in the 0.3-mg group
      than in the 0.15-mg group. When the results for the 0.3- and 0.15-mg groups were
      combined, the percentage of change in serum lipid levels at 48 weeks remained as
      stable as at 12 weeks. No serious adverse reactions were observed. We concluded
      that the higher dose of cerivastatin sodium was more effective than the lower
      dose, with comparable tolerability, in the treatment of patients with severe
      primary hypercholesterolemia.

PMID- 9663371
TI  - Outcomes and cost benefits associated with the introduction of inhaled
      corticosteroid therapy in a medicaid population of asthmatic patients.
AB  - A retrospective cohort study was conducted to assess the clinical and economic
      impact of the introduction of inhaled corticosteroid therapy in the North
      Carolina Medicaid population of patients with asthma. The case group consisted of
      180 patients who were followed for 1 year before and 1 year after the initiation
      of inhaled corticosteroid therapy. The control group consisted of 233 patients
      whose asthma was of similar severity to that of the case group and who remained
      on any therapy other than corticosteroids for a continuous 2-year period. After
      the initiation of inhaled corticosteroid therapy, the case group had reductions
      of 50% in hospitalizations, 26% in outpatient visits, and 15% in physician
      visits. At the end of the second year, the control group had significant
      increases of 23% in hospitalizations and 36% in outpatient visits. All of the
      changes were statistically significant. However, after adjusting for potential
      confounding factors, there was a nearly 24% decrease in total health care costs
      per asthmatic patient per month as a result of the introduction of inhaled
      corticosteroid therapy. Overall, we found that there was a cost benefit to
      Medicaid in the introduction of inhaled corticosteroid therapy and that this
      therapy brought about dramatic decreases in health care utilization and costs.

PMID- 9663372
TI  - The effect on costs of the use of half-dose aprotinin for first-time reoperative
      coronary artery bypass patients.
AB  - Half-dose aprotinin previously has been shown to reduce bleeding and the need for
      blood transfusions, but the results of cost-reduction studies have been variable.
      The purpose of the present retrospective study was to compare, from the
      perspective of the acute care hospital as health care provider, the costs
      associated with first-time reoperative coronary artery bypass graft (CABG)
      surgery in patients who received half-dose aprotinin with the costs in those who
      did not. Medical records from 46 historical controls (first-time reoperative CABG
      patients receiving no aprotinin) and 51 half-dose aprotinin-treated patients were
      reviewed. A total of 36 variables were abstracted from the medical records for
      analysis. It was found that more aprotinin-treated patients did not require
      transfusion compared with nontreated patients (47% vs 26%). Twenty-one percent
      fewer aprotinin-treated patients received red blood cell transfusions, 21% fewer
      received plateletpheresis packs, and 19% fewer received fresh frozen plasma. Cost
      savings per patient receiving half-dose aprotinin compared with no aprotinin were
      approximately $878 in blood products and $1088 in total length of stay (including
      critical care), for total savings of $1966. When the cost of aprotinin ($450) was
      subtracted, the approximate net mean savings per patient were $1516. This did not
      include additional cost savings with aprotinin resulting from a median 19.5
      minute shorter pump time. The authors conclude that the use of half-dose
      aprotinin results in reductions in surgical and associated hospitalization costs
      because of decreases in the length of hospital stay, including length of stay in
      critical care, and in the use of blood products.

PMID- 9663373
TI  - Cost comparisons between nafarelin and leuprolide in the treatment of
      endometriosis.
AB  - The objective of this study was to compare the cost and effectiveness of
      nafarelin versus leuprolide in the treatment of endometriosis. To compare the
      economic impact of treating endometriosis with leuprolide or nafarelin and to
      facilitate cost comparisons between the two, we statistically analyzed
      information concerning the costs of medications for the treatment of
      endometriosis, outpatient services, and management of adverse effects, as well as
      other related costs. A national claims database, MarketScan, was used to obtain
      data on patients with a principal diagnosis of endometriosis who were treated
      with either leuprolide or nafarelin. During the calendar years 1992-1994, 114
      patients with endometriosis had claims for nafarelin, and 343 had claims for
      leuprolide. There were no significant differences between nafarelin and
      leuprolide recipients with respect to demographic variables, types of concomitant
      drug used, types of outpatient service received, or major outpatient diagnostic
      categorization. In 1994 dollars, the cost of using leuprolide was $326.7 greater
      than that of using nafarelin. The results of this study suggest that nafarelin is
      a less expensive alternative to leuprolide for the treatment of endometriosis.

PMID- 9663374
TI  - Psychotropic prescribing for the elderly in office-based practice.
AB  - This study employed data from the National Ambulatory Medical Care Survey (NAMCS)
      1995 to (1) determine the prevalence of the prescribing of psychotropic drugs for
      elderly patients by office-based physicians in the United States; (2) estimate
      the prevalence of the prescribing of potentially inappropriate psychotropic drugs
      in this patient population; and (3) identify any factors that predict such
      prescribing. For the purposes of this study, previously developed consensus
      criteria were adopted defining inappropriate psychotropic drugs as those that
      should be avoided in the elderly. According to the NAMCS data, psychotropic
      medications were prescribed in an estimated 12.02 million visits by elderly
      patients (95% confidence interval [CI], 11.07-12.97 million). The psychotropic
      medications most frequently prescribed for elderly patients by office-based
      physicians were antidepressants and antianxiety agents. The occurrence of visits
      at which psychotropic medications were prescribed was greater in patients who
      were over 84 years of age, female, white, or from the western United States.
      Primary care physicians prescribed the majority of these psychotropic drugs, and
      most visits to psychiatrists by elderly patients resulted in the prescribing of
      psychotropic drugs. Office-based physicians prescribed at least one potentially
      inappropriate psychotropic medication in 2.03 million visits by the elderly (95%
      CI, 1.70-2.36 million), or 16.87% of visits by the elderly involving
      prescriptions for psychotropic drugs. The most frequently prescribed potentially
      inappropriate psychotropic drugs were amitriptyline and long-acting
      benzodiazepines such as diazepam, chlordiazepoxide, and flurazepam. Logistic
      regression analyses revealed that inappropriate prescribing of psychotropic drugs
      for elderly patients was associated with particular patient characteristics
      (visit due to an injury), drug characteristics (number of medications prescribed
      and the drug being an antidepressant or antianxiety agent), and physician
      characteristics (psychiatric specialty and location in the South or Northeast).
      The patterns of psychotropic prescribing found in the ambulatory setting raise
      concerns about the quality of care being received by elderly patients with
      psychiatric illnesses.

PMID- 9663375
TI  - Rote learning after exposure to a direct-to-consumer television advertisement for
      a prescription drug.
AB  - The purpose of this exploratory study was to: (1) test the rote learning
      response; and (2) investigate the effects of selected consumer
      demographic/psychographic, information-access, and health-related
      knowledge/experience variables on rote learning after exposure to a televised
      direct-to-consumer prescription drug advertisement that was developed and
      broadcast under new US Food and Drug Administration guidelines. A judgment
      (nonprobability) sample of 202 individuals waiting for their appointments at a
      university-based general medicine clinic was selected to view a televised
      advertisement and complete a questionnaire. One participant returned an unusable
      form; 24 others held positions in health care occupations and were omitted from
      the analysis. Results based on responses from the 177 eligible participants
      showed that the presentation of both promotional and risk-related product
      information in the same broadcast advertisement may lead to viewer problems with
      rote learning of each type of information.

PMID- 9663376
TI  - Molecular and cellular effects of ultraviolet light-induced genotoxicity.
AB  - Exposure to the solar ultraviolet spectrum that penetrates the Earth's
      stratosphere (UVA and UVB) causes cellular DNA damage within skin cells. This
      damage is elicited directly through absorption of energy (UVB), and indirectly
      through intermediates such as sensitizer radicals and reactive oxygen species
      (UVA). DNA damage is detected as strand breaks or as base lesions, the most
      common lesions being 8-hydroxydeoxyguanosine (8OHdG) from UVA exposure and
      cyclobutane pyrimidine dimers from UVB exposure. The presence of these products
      in the genome may cause misreading and misreplication. Cells are protected by
      free radical scavengers that remove potentially mutagenic radical intermediates.
      In addition, the glutathione-S-transferase family can catalyze the removal of
      epoxides and peroxides. An extensive repair capacity exists for removing (1)
      strand breaks, (2) small base modifications (8OHdG), and (3) bulky lesions
      (cyclobutane pyrimidine dimers). UV also stimulates the cell to produce early
      response genes that activate a cascade of signaling molecules (e.g., protein
      kinases) and protective enzymes (e.g., haem oxygenase). The cell cycle is
      restricted via p53-dependent and -independent pathways to facilitate repair
      processes prior to replication and division. Failure to rescue the cell from
      replication block will ultimately lead to cell death, and apoptosis may be
      induced. The implications for UV-induced genotoxicity in disease are considered.

PMID- 9663377
TI  - Hemochromatosis: new insights in pathogenesis and diagnosis following the
      discovery of the gene.
AB  - Hemochromatosis is a common and often underdiagnosed disease. Early diagnosis and
      treatment results in an excellent long-term prognosis. The development of a
      diagnostic genetic test has improved the feasibility of the goal of prevention of
      morbidity and mortality from hemochromatosis.

PMID- 9663378
TI  - A colipase fold in the carboxy-terminal domain of the Wnt antagonists--the
      Dickkopfs.

PMID- 9663379
TI  - Protein folding: think globally, (inter)act locally.

PMID- 9663380
TI  - Plant development: Medea's maternal instinct.
AB  - The Arabidopsis MEDEA gene is required in maternal tissues to restrict cell
      proliferation in embryos. Molecular characterisation indicates that MEDEA encodes
      a Polycomb-group protein, particularly intriguing as MEDEA's maternal effects may
      be a consequence of genomic imprinting.

PMID- 9663381
TI  - Biological motors: energy storage in myosin molecules.
AB  - A recent experiment of exceptional complexity has shown that a myosin may lose
      its ATP but store the energy from it and attach to actin and perform a working
      stroke several hundred milliseconds later.

PMID- 9663382
TI  - Visuomotor control: where does vision end and action begin?
AB  - A new understanding of how visual information is transformed into motor acts has
      emerged from recent studies of the organization of the visuomotor pathways in the
      primate brain. This work suggests that it may no longer be useful, or even
      correct, to categorize different brain areas as sensory or motor.

PMID- 9663383
TI  - Telomeres: moonlighting by DNA repair proteins.
AB  - Chromosome ends, or telomeres, are dynamic DNA structures maintained by a
      multisubunit telomerase and other proteins. New evidence indicates that proteins
      previously implicated in the repair of DNA doublestrand breaks also play an
      important role in the control of telomere organization and length.

PMID- 9663384
TI  - Ribozymes: the hammerhead swings into action.
AB  - A new crystal structure of a modified hammerhead ribozyme reveals an intermediate
      conformation that may explain discrepancies between previous structures and the
      required orientation of the labile bond in the ribozyme's active site.

PMID- 9663385
TI  - Anti-viral immunity: spotting virus-specific T cells.
AB  - Historically, quantitation of virus-specific CD8+ T cells has been accomplished
      by limiting dilution analysis of cytotoxic precursor cells. Recent studies have
      shown that this technique greatly underestimates the actual number of antigen
      specific cells and have provided new insight into anti-viral immune responses.

PMID- 9663386
TI  - Adaptive evolution: the struggle for dominance.
AB  - Although wild-type alleles are generally dominant over mutant alleles, recently
      established alleles for pesticide resistance are rarely recessive in combination
      with their progenitors. This seems to be caused by a combination of a 'selective
      sieve' favouring non-recessive mutations, and the biochemical basis of
      resistance.

PMID- 9663387
TI  - Sensitivity to dynamic auditory and visual stimuli predicts nonword reading
      ability in both dyslexic and normal readers.
AB  - BACKGROUND: Developmental dyslexia is a specific disorder of reading and spelling
      that affects 3-9% of school-age children and adults. Contrary to the view that it
      results solely from deficits in processes specific to linguistic analysis,
      current research has shown that deficits in more basic auditory or visual skills
      may contribute to the reading difficulties of dyslexic individuals. These might
      also have a crucial role in the development of normal reading skills. Evidence
      for visual deficits in dyslexia is usually found only with dynamic and not static
      stimuli, implicating the magnocellular pathway or dorsal visual stream as the
      cellular locus responsible. Studies of such a dissociation between the processing
      of dynamic and static auditory stimuli have not been reported previously.
      RESULTS: We show that dyslexic individuals are less sensitive both to particular
      rates of auditory frequency modulation (2 Hz and 40 Hz but not 240 Hz) and to
      dynamic visual-motion stimuli. There were high correlations, for both dyslexic
      and normal readers, between their sensitivity to the dynamic auditory and visual
      stimuli. Nonword reading, a measure of phonological awareness believed crucial to
      reading development, was also found to be related to these sensory measures.
      CONCLUSIONS: These results further implicate neuronal mechanisms that are
      specialised for detecting stimulus timing and change as being dysfunctional in
      many dyslexic individuals. The dissociation observed in the performance of
      dyslexic individuals on different auditory tasks suggests a sub-modality division
      similar to that already described in the visual system. These dynamic tests may
      provide a non-linguistic means of identifying children at risk of reading
      failure.

PMID- 9663388
TI  - Endoplasmic reticulum membrane tubules are distributed by microtubules in living
      cells using three distinct mechanisms.
AB  - BACKGROUND: The microtubule-dependent motility of endoplasmic reticulum (ER)
      tubules is fundamental to the structure and function of the ER. From in vitro
      assays, three mechanisms for ER tubule motility have arisen: the 'membrane
      sliding mechanism' in which ER tubules slide along microtubules using microtubule
      motor activity; the 'microtubule movement mechanism' in which ER attaches to
      moving microtubules; and the 'tip attachment complex (TAC) mechanism' in which ER
      tubules attach to growing plus ends of microtubules. RESULTS: We have used multi
      wavelength time-lapse epifluorescence microscopy to image the dynamic
      interactions between microtubules (by microinjection of X-rhodamine-labeled
      tubulin) and ER (by DiOC6(3) staining) in living cells to determine which
      mechanism contributes to the formation and motility of ER tubules in migrating
      cells in vivo. Newly forming ER tubules extended only in a microtubule plus-end
      direction towards the cell periphery: 31.4% by TACs and 68.6% by the membrane
      sliding mechanism. ER tubules, statically attached to microtubules, moved towards
      the cell center with microtubules through actomyosin-based retrograde flow. TACs
      did not change microtubule growth and shortening velocities, but reduced
      transitions between these states. Treatment of cells with 100 nM nocodazole to
      inhibit plus-end microtubule dynamics demonstrated that TAC motility required
      microtubule assembly dynamics, whereas membrane sliding and retrograde-flow
      driven ER motility did not. CONCLUSIONS: Both plus-end-directed membrane sliding
      and TAC mechanisms make significant contributions to the motility of ER towards
      the periphery of living cells, whereas ER removal from the lamella is powered by
      actomyosin-based retrograde flow of microtubules with ER attached as cargo. TACs
      in the ER modulate plus-end microtubule dynamics.

PMID- 9663389
TI  - Expression pattern of a butterfly achaete-scute homolog reveals the homology of
      butterfly wing scales and insect sensory bristles.
AB  - BACKGROUND: Lepidopteran wing scales are the individual units of wing color
      patterns and were a key innovation during Lepidopteran evolution. On the basis of
      developmental and morphological evidence, it has been proposed that the sensory
      bristles of the insect peripheral nervous system and the wing scales of
      Lepidoptera are homologous structures. In order to determine if the developmental
      pathways leading to Drosophila sensory bristle and butterfly scale formation use
      similar genetic circuitry, we cloned, from the butterfly Precis coenia, a homolog
      of the Drosophila achaete-scute (AS-C) genes--which encode transcription factors
      that promote neural precursor formation--and examined its expression pattern
      during development. RESULTS: During embryonic and larval development, the
      expression pattern of the AS-C homolog, ASH1, forecasted neural precursor
      formation. ASH1 was expressed both in embryonic proneural clusters--within which
      an individual cell retained ASH1 expression, enlarged, segregated, and became a
      neural precursor--and in larval wing discs in putative sensory mother cells. ASH1
      was also expressed in pupal wings, however, in evenly spaced rows of enlarged
      cells that had segregated from the underlying epidermis but, rather than give
      rise to neural structures, each cell contributed to an individual scale.
      CONCLUSIONS: ASH1 appears to perform multiple functions throughout butterfly
      development, apparently promoting the initial events of selection and formation
      of both neural and scale precursor cells. The similarity in the cellular and
      molecular processes of scale and neural precursor formation suggests that the
      spatial regulation of an AS-C gene was modified during Lepidopteran evolution to
      promote scale cell formation.

PMID- 9663390
TI  - Regulation of beta 1-integrin-mediated cell adhesion by the Cbl adaptor protein.
AB  - BACKGROUND: Leukocyte activation results in a rapid increase in adhesion to the
      extracellular matrix due to the activation of beta 1 integrin receptors. A role
      for phosphatidylinositol (PI) 3-kinase in integrin activation has been proposed,
      as activation of integrins by many receptors can be blocked by PI 3-kinase
      inhibitors. One receptor that regulates integrins is the CD28 surface antigen;
      here, we investigated the mechanisms responsible for CD28-mediated integrin
      activation. RESULTS: CD28-mediated integrin activation was blocked by mutation of
      the binding site for the p85 catalytic subunit of PI 3-kinase in the CD28
      cytoplasmic domain, and by expression of a dominant-negative form of the p85
      subunit. Substitution of the Src homology 2 (SH2)-binding motif in the CD28
      cytoplasmic domain for the corresponding motif in the CD28-related CTLA-4 surface
      antigen also blocked integrin activation but did not affect the recruitment and
      activation of PI 3-kinase. Mutations of the CD28 cytoplasmic domain that blocked
      integrin activation also impaired the tyrosine phosphorylation of the Cbl adaptor
      protein and the activation of the PI 3-kinase that was associated with Cbl. This
      Cbl-associated PI 3-kinase was distinct from the PI 3-kinase that coprecipitated
      with the CD28 cytoplasmic domain. CD28-mediated activation of beta 1 integrins
      was inhibited by expression of a mutant Cbl protein that shows reduced
      association with PI 3-kinase. CONCLUSIONS: Cbl is required for PI-3-kinase
      dependent regulation of integrin receptors by CD28. Furthermore, CD28 is coupled
      to two distinct pools of PI 3-kinase, one directly associated with the CD28
      cytoplasmic tail and the other associated with Cbl.

PMID- 9663391
TI  - Sequence-based design of a peptide probe for the APC tumor suppressor protein.
AB  - BACKGROUND: Proteins form specific associations, but predictive rules for protein
      pairing are generally unknown. Here, we describe amino-acid sequence patterns
      capable of mediating specific pairing of a widespread protein motif: the
      parallel, dimeric, alpha-helical coiled coil. The pairing rules were tested by
      designing a 54-residue peptide (anti-APCp1) that is predicted to dimerize
      preferentially with a coiled-coil sequence from the adenomatous polyposis coli
      (APC) tumor suppressor protein. RESULTS: As judged by circular dichroism,
      ultracentrifugation and native gel electrophoresis, anti-APCp1 formed a specific,
      helical, dimeric complex with the target APC coiled coil. On western blots of APC
      fragments expressed in Escherichia coli, the designed peptide detected a pattern
      of bands identical to the pattern detected by an antibody directed against the
      APC coiled coil. Peptide-mediated precipitation experiments showed that anti
      APCp1 bound and sequestered wild-type and mutant APC proteins in extracts of
      human colon cancer cell lines. In addition, binding of the designed peptide
      preserved native APC-beta-catenin complexes. CONCLUSIONS: These biochemical
      experiments demonstrate that the anti-APC peptide preferentially forms a
      heterodimeric coiled coil with mutant and full-length APC proteins. The
      specificity of the designed peptide is sufficient to support several applications
      that commonly use antibodies. The observed specificity of anti-APCp1 validates
      the pairing rules used as the basis for the probe design, and it suggests that
      residues in the core positions of coiled coils help impart pairing selectivity.

PMID- 9663392
TI  - The yeast Ku heterodimer is essential for protection of the telomere against
      nucleolytic and recombinational activities.
AB  - The Ku heterodimer, conserved in a wide range of eukaryotes, plays a multiplicity
      of roles in yeast. First, binding of Ku, which is composed of a 70 kDa (Hdf1p)
      and an 80 kDa (Hdf2p) subunit [1-3], to double-strand breaks promotes non
      homologous end-to-end joining of DNA [3]. Second, Ku appears to participate in
      DNA replication, regulating both the number of rounds of replication permissible
      within the cell cycle and the structure of the initiation complex [3,4].
      Furthermore, mutations in HDF1 or HDF2 rapidly reduce telomeric poly (TG1-3)
      tract size [1-3], hinting also at a possible telomeric function of Ku. We show
      here that the two subunits of the Ku heterodimer play a key role in maintaining
      the integrity of telomere structure. Mutations in either Ku subunit increased the
      single-strandedness of the telomere in a cell-cycle-independent fashion, unlike
      wild-type cells which form 3' poly(TG1-3) overhangs exclusively in late S phase
      [5]. In addition, mutations enhanced the instability of elongated telomeres to
      degradation and recombination. Both Ku subunits genetically interacted with the
      putative single-stranded telomere-binding protein Cdc13p. We propose that Ku
      protects the telomere against nucleases and recombinases.

PMID- 9663393
TI  - Phospholipase D1 localises to secretory granules and lysosomes and is plasma
      membrane translocated on cellular stimulation.
AB  - Phospholipase D (PLD) activity has been implicated in the regulation of membrane
      trafficking [1,2], superoxide generation and cytoskeletal remodelling [3,4].
      Several PLD genes have now been identified and it is probable that different
      isoforms regulate distinct functions. Defining the subcellular localisation of
      each isoform would facilitate understanding of their roles. Previous PLD
      localisation studies have been based largely on enzyme activity measurements,
      which cannot distinguish between isoforms [2,5]. We have cloned the cDNAs
      encoding human PLD1a and PLD1b from an HL60 cell cDNA library and expressed them
      as catalytically active fusion proteins with green fluorescent protein (GFP) in
      COS-1 cells and RBL-2H3 cells, a mast cell model which degranulates upon cross
      linking of the high-affinity immunoglobulin E (IgE) receptor. In unstimulated
      cells, GFP-PLD1b colocalised with secretory granule and lysosomal markers; it was
      not found at the plasma membrane or nucleus and did not colocalise with markers
      for the Golgi. Stimulation or RBL-2H3 cells through IgE receptor cross-linking
      caused plasma membrane recruitment of GFP-PLD1b. Inhibition of IgE-receptor
      stimulated, PLD-catalysed phosphatidate formation suppressed secretion of granule
      and lysosomal contents, but did not affect translocation of GFP-PLD1b. These
      experiments suggest that PLD1 plays a role in regulated exocytosis rather than
      endoplasmic reticulum (ER) to Golgi membrane transport.

PMID- 9663394
TI  - Ras-independent activation of Ral by a Ca(2+)-dependent pathway.
AB  - The RalA and RalB proteins comprise a distinct family of small GTPases [1]. Ral
      specific guanine-nucleotide exchange factors such as RalGDS, Rlf and RGL interact
      with activated Ras and cooperate with Ras in the transformation of murine
      fibroblasts [2-5]. Thus, the interaction of RalGDS with Ras and the subsequent
      activation of Ral are thought to constitute a distinct Ras-dependent signaling
      pathway. The function of Ral is largely unknown. There is circumstantial evidence
      that Ral may have a function in regulating the cytoskeleton through its
      interaction with RIP1 (also known as RLIP or RalBP1), a GTPase-activating protein
      specific for the small GTPases Cdc42 and Rac [6-8]. Ral also binds to
      phospholipase D (PLD) and thus may play a role in signaling through phospholipids
      [9]. We have examined endogenous levels of activated, GTP-bound Ral (Ral-GTP) in
      Rat-2 fibroblasts stimulated with various mitogens. Lysophosphatidic acid (LPA)
      and epidermal growth factor (EGF), which activate both Ras-dependent and Ras
      independent signaling pathways [10,11], rapidly activated Ral. Inhibition of Ras
      activation by dominant-negative Ras (RasS17N) or pertussis toxin had little
      effect on Ral-GTP levels, however. Ral was activated by the Ca2+ ionophore
      ionomycin, and activation by LPA or EGF could be blocked by a phospholipase C
      (PLC) inhibitor. The results presented here demonstrate a Ca(2+)-dependent
      mechanism for the activation of Ral.

PMID- 9663395
TI  - A multiple subunit Mi-2 histone deacetylase from Xenopus laevis cofractionates
      with an associated Snf2 superfamily ATPase.
AB  - Chromatin structure plays a crucial regulatory role in the control of gene
      expression. In eukaryotic nuclei, enzymatic complexes can alter this structure by
      both targeted covalent modification and ATP-dependent chromatin remodeling.
      Modification of histone amino termini by acetyltransferases and deacetylases
      correlates with transcriptional activation and repression [1-3], cell growth [4],
      and tumorigenesis [5]. Chromatin-remodeling enzymes of the Snf2 superfamily use
      ATP hydrolysis to restructure nucleosomes and chromatin, events which correlate
      with activation of transcription [6,7]. We purified a multi-subunit complex from
      Xenopus laevis eggs which contains six putative subunits including the known
      deacetylase subunits Rpd3 and RbAp48/p46 [8] as well as substoichiometric
      quantities of the deacetylase-associated protein Sin3 [9-13]. In addition, we
      identified one of the other components of the complex to be Mi-2, a Snf2
      superfamily member previously identified as an autoantigen in the human
      connective tissue disease dermatomyositis [14,15]. We found that nucleosome
      stimulated ATPase activity precisely copurified with both histone deacetylase
      activity and the deacetylase enzyme complex. This association of a histone
      deacetylase with a Snf2 superfamily ATPase suggests a functional link between
      these two disparate classes of chromatin regulators.

PMID- 9663396
TI  - The Human Genome Epidemiology Network.

PMID- 9663397
TI  - Eating patterns and risk of colon cancer.
AB  - Colon cancer has been associated with several nutrients and foods. The authors
      used data from a population-based study conducted in Northern California, Utah,
      and Minnesota to examine associations between dietary eating patterns and risk of
      developing colon cancer. Through factor analysis, detailed dietary intake data
      obtained from 1,993 cases (diagnosed in 1991-1994) and 2,410 controls were
      grouped into factors that were evaluated for relations with lifestyle
      characteristics and colon cancer risk. Several dietary patterns emerged. The
      dietary patterns with the most variation were labeled "Western," "prudent," "high
      fat/sugar dairy," "substituters," and "drinkers." The "Western" dietary pattern
      was associated with a higher body mass index and a greater intake of total energy
      and dietary cholesterol. The "prudent" pattern was associated with higher levels
      of vigorous leisure time physical activity, smaller body size, and higher intakes
      of dietary fiber and folate. Persons who had high scores on the "drinker" pattern
      were also more likely to smoke cigarettes. The "Western" dietary pattern was
      associated with an increased risk of colon cancer in both men and women. The
      association was strongest among people diagnosed prior to age 67 years (for men,
      odds ratio (OR)=1.96, 95% confidence interval (CI) 1.22-3.15; for women, OR=2.02,
      95% CI 1.21-3.36) and among men with distal tumors (OR=2.25, 95% CI 1.47-3.46).
      The "prudent" diet was protective, with the strongest associations being observed
      among people diagnosed prior to age 67 years (men: OR=0.63, 95% CI 0.43-0.92;
      women: OR=0.58, 95% CI 0.38-0.87); associations with this dietary pattern were
      also strong among persons with proximal tumors (men: OR=0.55, 95% CI 0.38-0.80;
      women: OR=0.64, 95% CI 0.45-0.92). Although "substituters" (people who
      substituted low fat dairy products for high fat dairy products, margarine for
      butter, poultry for red meat, and whole grains for refined grains) were at
      reduced risk of colon cancer, the reduction in risk was not statistically
      significant. These data support the hypothesis that overall dietary intake
      pattern is associated with colon cancer, and that the dietary pattern associated
      with the greatest increase in risk is the one which typifies a Western-style
      diet.

PMID- 9663398
TI  - Invited commentary: Factor analysis and the search for objectivity.

PMID- 9663399
TI  - The senior authors' response: Factor analysis as a tool for evaluating eating
      patterns.

PMID- 9663400
TI  - Bone mineral density and risk of breast cancer: differences by family history of
      breast cancer. Study of Osteoporotic Fractures Research Group.
AB  - Recent studies have suggested that bone mineral density (BMD) is related to risk
      of breast cancer in elderly women. This study investigated whether the level of
      breast cancer risk associated with BMD in women with a positive family history of
      breast cancer is different from that in women without a family history of breast
      cancer. Radial and calcaneus BMD were measured at baseline (1986-1988) in 7,250
      elderly white women enrolled in the Study of Osteoporotic Fractures, and initial
      breast cancer status was ascertained at year 1 of follow-up. After a mean of 3.2
      years of additional follow-up, 104 incident breast cancer cases, 20 of which
      appeared in women with a family history of breast cancer, were identified and
      confirmed by medical record review. Modification of the BMD effect by family
      history status was assessed by inclusion of interaction terms in proportional
      hazards regression models. Among women without a family history of breast cancer,
      those with a proximal radius BMD in the highest tertile were at a 1.48-fold
      increased risk compared with women in the lowest tertile; among women with a
      positive family history of breast cancer, those with highest tertile BMD were at
      a 3.41-fold increased risk compared with women in the lowest tertile. These
      results suggest that the association between BMD and breast cancer may be
      different in subgroups of women defined by family history.

PMID- 9663401
TI  - Maternal vitamin use, genetic variation of infant methylenetetrahydrofolate
      reductase, and risk for spina bifida.
AB  - Maternal periconceptional use of vitamin supplements containing folic acid
      substantially reduces the risk of neural tube defects (NTDs) in the offspring.
      The mechanism underlying this reduction in risk is unknown. Several recent
      studies have reported an association between homozygosity for a variant form (the
      C677T genotype) of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene and
      risk for NTDs in individuals. It has been hypothesized that maternal folic acid
      supplementation prevents NTDs by partially correcting reduced MTHFR activity
      associated with the variant form of the enzyme. Using data from two California
      case-control interview studies (1987-1991 birth cohorts), the authors
      investigated whether an interaction for spina bifida risk existed between infant
      MTHFR C677T genotype and maternal use of supplements containing folic acid. The
      authors genotyped the allelic variants of MTHFR in 214 liveborn case infants with
      spina bifida and 503 control infants for whom information on maternal
      periconceptional vitamin use was available. The percentage of all case infants
      with the C677T MTHFR mutation, for both homozygous (TT) and heterozygous (TC)
      genotypes, was slightly higher than that of controls. The C677T genotype was
      substantially more frequent among both case and control Hispanic infants than
      among non-Hispanic infants. Among all infants whose mothers did not
      periconceptionally use vitamins containing folic acid, the risk of spina bifida,
      as measured by the odds ratio, was 1.6 (95% confidence interval (CI) 0.8-3.1) for
      all infants with the TT genotype and 2.0 (95% CI 0.5-7.4) for non-Hispanic white
      infants with the TT genotype, as compared with infants with the CC genotype. This
      result indicates a modestly increased risk associated with the C677T genotype. A
      lower risk estimate (odds ratio=1.2, 95% CI 0.4-4.0) was observed among infants
      whose mothers periconceptionally used vitamin supplements containing folic acid.
      This population-based California study found a modestly increased risk of spina
      bifida among infants who were homozygous for the C677T genotype, but only minimal
      evidence of an interaction between the C677T genotype and maternal folic acid
      intake in the occurrence of spina bifida. If this mutant MTHFR genotype plays a
      role in the association between maternal vitamin use and NTD risk, it may be a
      small role, or it may be conditional on maternal genotype.

PMID- 9663402
TI  - Use of antioxidant supplements and its association with cognitive function in a
      rural elderly cohort: the MoVIES Project. Monongahela Valley Independent Elders
      Survey.
AB  - There has been much interest recently in the therapeutic benefits of
      antioxidants, including a possible protective role in preventing or delaying
      cognitive decline. This study describes the use of antioxidant supplements among
      1,059 rural, noninstitutionalized elderly residents of southwestern Pennsylvania
      who are participants in the Monongahela Valley Independent Elders Survey. The
      data were collected during the survey's second wave of follow-up (1989-1991). The
      mean age of participants was 74.5 years (standard deviation 5.5), and 57.3% were
      women. Current use of nutritional supplements containing vitamin A, C, or E, beta
      carotene, zinc, or selenium was measured through self-report. Subjects were
      administered a battery of 15 neuropsychological tests measuring performance in
      several cognitive domains. Of the 1,059 persons, 342 (32.3%) were taking
      antioxidant supplements. Women and persons with higher levels of education were
      more often antioxidant users. Antioxidant use did not vary significantly by age,
      race, or income. In univariate analyses, antioxidant use was significantly and
      positively associated with performance on several cognitive tests. However, after
      adjustment for age, education, and sex, there were no significant differences in
      cognitive test performance between antioxidant users and nonusers. This study is
      one of only a few that have analyzed the relation between antioxidants and
      cognition in a community-based sample. After potentially confounding factors are
      accounted for, the results do not support the hypothesis that antioxidant
      supplement use is associated with cognitive function.

PMID- 9663403
TI  - Cohort study of vitamin C intake and cognitive impairment.
AB  - To test the hypothesis that vitamin C protects against cognitive impairment, the
      authors conducted a cohort study (n=117) in a retirement community in Sydney,
      Australia. Vitamin C intake was assessed at baseline (1991) with a
      semiquantitative food frequency questionnaire, and cognitive function was
      assessed 4 years later (1995). After adjustment for age, sex, smoking, education,
      total energy intake, and use of psychotropic medications, consumption of vitamin
      C supplements was associated with a lower prevalence of more severe cognitive
      impairment (based on scores on the Mini-Mental State Examination; adjusted odds
      ratio=0.39, 95% confidence interval 0.18-0.84). There were no associations
      between vitamin C intake and scores on tests of verbal and category fluency. This
      study suggests that vitamin C might protect against cognitive impairment.

PMID- 9663404
TI  - Incidence of dementia and Alzheimer's disease: a reanalysis of data from
      Rochester, Minnesota, 1975-1984.
AB  - For both dementia and Alzheimer's disease (AD), data regarding incidence rates in
      the oldest old and time trends in incidence are limited. The authors reanalyzed
      previously reported data on the incidence of dementia and AD in Rochester,
      Minnesota, from 1975 through 1984, using three new strategies. First, incidence
      rates were corrected by removing age-, sex-, and calendar year-specific prevalent
      cases from the census-derived denominator figures. Second, incidence figures for
      persons above age 84 years were disaggregated. Third, time trends were
      investigated graphically using age-specific curves and birth cohort curves.
      Dementia diagnosis and AD diagnosis followed defined ad hoc criteria. Analyses
      were conducted for men, women, and both sexes combined, and for dementia and AD
      separately. The age-specific incidence rates were similar in men and women,
      continued to increase after age 84 years, and remained stable over time for both
      dementia and AD. No birth cohort effect was present for either dementia or AD.
      The similar risks seen in men and women, the continuing increase in incidence
      after age 84 years, and the stability of incidence over time have important
      implications for etiologic research on AD.

PMID- 9663405
TI  - Predictors of onset of and recovery from mobility difficulty among adults aged 51
      61 years.
AB  - Relative to information on activities of daily living, information regarding the
      onset of and recovery from mobility difficulty has been limited. Drawing upon
      data gathered from 6,376 self-respondents aged 51-61 years at baseline (1992) who
      were successfully reinterviewed in 1994 as part of the Health and Retirement
      Survey, the authors were able to build upon and add to knowledge gained from
      previous studies of the onset of and recovery from mobility difficulty.
      Hierarchical logistic regression was used to separate the direct and indirect
      effects of predictors of mobility difficulty onset and recovery at 2-year follow
      up. To separate direct and indirect effects, the authors categorized various
      predictors as being related to sociodemographic factors, economic factors, health
      behavior, chronic disease, or physical impairment, and the categories were
      sequentially incorporated into a series of equations. The order in which the
      predictors were incorporated into the equations followed from a theoretical model
      of the disability process. In this study of mobility difficulty, the strongest
      direct predictors of recovery were having little baseline difficulty and the
      absence of diabetes mellitus, lung disease, and frequent pain. The strongest
      direct predictors of onset were female sex, less education, low net worth, lack
      of private health insurance, obesity, and frequent pain. Few indirect predictors
      for either onset or recovery were identified. Predictors of recovery were few and
      differed from predictors of onset. Further efforts are needed to identify
      modifiable predictors among females, persons with few economic resources, and
      those with frequent pain.

PMID- 9663406
TI  - Factor analysis of unexplained severe fatigue and interrelated symptoms: overlap
      with criteria for chronic fatigue syndrome.
AB  - The objective of this study was to identify factors explaining the correlations
      among unexplained severe fatigue of different durations (1-5 months or > or =6
      months) and symptoms reported as being significant health problems during a
      preceding 4-week period. Between June and December of 1994, a cross-sectional,
      random digit dialing telephone survey was conducted among residents of San
      Francisco, California. All subjects who reported having severe fatigue lasting
      for > or =1 month and a random sample of nonfatigued subjects were asked to
      participate in a detailed telephone interview. Data from 1,510 individuals aged
      18-60 years who did not have medical or psychiatric conditions that could explain
      their severe fatigue were analyzed. Common factor analyses identified three
      correlated factors (defined as "fatigue-mood-cognition" symptoms, "flu-type"
      symptoms, and "visual impairment") that explained the correlations among fatigue
      lasting for > or =6 months and 14 interrelated symptoms. No factor explained the
      correlations among fatigue lasting for 1-5 months and other symptoms. The
      combination of fatigue of > or =6 months' duration and selected symptoms overlaps
      with published criteria used to define cases of chronic fatigue syndrome (CFS).
      Although symptoms described in this study were reported as appearing within the
      preceding month, and CFS symptoms must have been present for the previous 6
      months, these results provide empirical support for the interrelations among
      unexplained fatigue of > or =6 months' duration and symptoms included in the CFS
      case definition.

PMID- 9663407
TI  - Epidemiology of rodent bites and prediction of rat infestation in New York City.
AB  - The authors examined the epidemiology of rodent bites occurring in New York City
      from 1986 through 1994 to identify factors contributing to increased probability
      of rodent bite and rat infestation. City blocks on which a rodent bite case had
      been reported (n=415) and three control blocks per bite block, matched by borough
      and randomly selected, were compared according to demographic characteristics
      obtained from US Census data. Environmental variables were defined using a
      geographic information system to extract distances to areas potentially providing
      food or refuge for rats, such as parks. Borough-specific models of bite risk were
      generated by logistic regression using data collected from 1991 to 1994; risk
      values were then generated for all city blocks. Field surveys for signs of rat
      infestation conducted on 31 randomly selected blocks indicated a significant
      association between degree of infestation and predicted risk. Spatial analyses
      comparing neighboring blocks showed that blocks with bite cases were
      significantly clustered. The models based on data from previous years correctly
      predicted 72 percent of 53 block addresses of rodent bite cases from 1995 as
      being locations of high or intermediate risk. A combination of geographic and
      epidemiologic analyses could help investigators identify the spatial occurrence
      of rat infestation over a large area and might help to focus control activities.

PMID- 9663408
TI  - Heterosexual transmission of human immunodeficiency virus: variability of
      infectivity throughout the course of infection. European Study Group on
      Heterosexual Transmission of HIV.
AB  - Although individuals infected with human immunodeficiency virus (HIV) seem to be
      more infectious in the late stages of HIV infection and possibly also during the
      seroconversion period, most estimates of per-sexual-contact infectivity have been
      obtained without allowing for variability over the course of infection. In this
      analysis, a probabilistic model was fitted to data from a European study carried
      out between 1987 and 1992 that involved 499 (359 males and 140 females) HIV
      infected subjects (index cases) and their regular heterosexual partners. The
      model used allowed infectivity (the per-sexual-contact HIV transmission
      probability, mu) to vary through three stages: the first 3 months following
      infection, the subsequent asymptomatic period, and the advanced stage (HIV
      related clinical symptoms or a CD4-positive T lymphocyte count less than
      200/mm3). Male-to-female infectivity through penile-anal sex was found to be
      higher in both the early and advanced stages of infection (mu=0.183) than in the
      longer intermediate period (mu=0.014) (p < 0.03). Failure to demonstrate
      significant differences between stages for other types of contact (male-to-female
      penile-vaginal contacts: mu=0.0007; female-to-male transmission: mu=0.0005) may
      reflect insufficient power rather than a true lack of variability. Indeed, the
      results for penile-anal sex suggest that persons who are in the process of
      seroconverting may be much more infectious than asymptomatic infected persons,
      whatever the type of contact. Prevention education should stress the risk of HIV
      transmission from subjects who may be unaware of their infection.

PMID- 9663409
TI  - Improvement in cumulative response rates following implementation of a financial
      incentive.
AB  - Risk estimates arising from case-control studies can be unreliable if the level
      of response to mailed questionnaires is inadequate. Several studies have reported
      improved early response rates to mailed questionnaires following the
      implementation of financial incentives. Improvements in cumulative response rates
      at the completion of the follow-up period, however, have not been as pronounced.
      A financial incentive of $5.00 was implemented among control subjects in a large
      population-based case-control study of Ontario, Canada, women. Required follow-up
      time and effort were decreased for the controls who received the incentive
      compared with those who did not. More importantly, cumulative response rates
      after more than 20 weeks were 20 percent higher among controls who received the
      incentive.

PMID- 9663410
TI  - Re: "Racial differences in sarcoidosis incidence: a 5-year study in a health
      maintenance organization".

PMID- 9663411
TI  - Re: "Long-term prognosis of women after myocardial infarction".

PMID- 9663412
TI  - Re: "Comparison of effect estimates from a meta-analysis of summary data from
      published studies and from a meta-analysis using individual patient data for
      ovarian cancer studies".

PMID- 9663413
TI  - The last twenty-five years of the American Epidemiological Society: 1972-1996.
AB  - The American Epidemiological Society (AES) was founded in 1927. A history of the
      first 45 years of the Society was written in the early 1970s by Dr. John Rodman
      Paul (Yale J Biol Med 1973;46:1-84). The past 25 years have seen the AES continue
      as a small, relatively elite organization characterized by a membership of senior
      leaders in the field of epidemiology. The Society has continued to hold an annual
      meeting at which free, informed, and uninhibited discussion is encouraged. In
      this paper, the author presents an account of the affairs of the AES during the
      past quarter century.

PMID- 9663414
TI  - Prognosis and management strategies of lymphatic neoplasias in the elderly. II.
      Hodgkin's disease.
AB  - In Caucasians, Hodgkin's disease demonstrates constant incidence rates, with a
      first peak occurring in adolescents and in young adults, and a second peak in the
      elderly. Age is an important risk factor for overall survival of patients;
      staging strategies and treatment expose elderly patients to an even higher risk
      arising from surgical complications, death from secondary cancer and leukemia or
      lethal cardiac complications. In contrast to non-Hodgkin's lymphoma, optimal
      staging and treatment procedures have not yet been defined for this disease in
      elderly patients. However, due to the very poor prognosis of inadequately treated
      patients, treatment recommendations at present must be based on those for younger
      patients while keeping the individual risk profile in mind. If staging laparotomy
      is omitted, most patients will require a combined modality treatment. While in
      low-risk patients a reduced number of cycles with full-dose chemotherapy like
      ABVD (Adriblastina, bleomycin, vinblastine, dacarbazine) or of six cycles with
      less toxic drugs like VBM (vinblastine, bleomycin, methotrexate) followed by
      limited field radiotherapy may suffice, patients with well-defined risk factors
      will require a more prolonged chemotherapy. Currently, there is no evidence that
      C(M)OPP [cyclophosphamide (mustargen), vincristine, procarbazine,
      prednisone]/ABVD or ABVD may successfully be replaced by less toxic regimens.
      Therefore, further studies are required on the specific definition of biological
      age, the cost/benefit ratio of staging procedures and treatment and the influence
      of these strategies on the quality of life in the elderly.

PMID- 9663415
TI  - Transarterial chemotherapy with zinostatin stimalamer for hepatocellular
      carcinoma.
AB  - Zinostatin stimalamer (SMANCS) is a lipophilic intra-arterial chemotherapeutic
      agent for hepatocellular carcinoma (HCC). Thirty HCC patients underwent
      transcatheter arterial injection of 4 mg SMANCS-lipiodol emulsion. Their
      responses were evaluated by computed tomography 1 month after treatment. Complete
      response (CR) was defined as disappearance or 100% necrosis of all tumors.
      Partial response (PR) was defined as > or = 50% reduction and/or > or = 50%
      necrosis. We regarded the lipiodol accumulation in tumors as being necrotic. CR
      and PR were observed in 8 patients (27%) and 4 patients (13%), respectively, and
      the overall response rate (CR + PR/all patients) was 40% (12/30). Of 12 patients
      whose serum alpha-fetoprotein levels had been more than 200 ng/ml before
      treatment, 5 patients (42%) showed more than 50% reduction in this level within 1
      month after treatment. Toxicity was quite acceptable, although grade 4 toxicity
      (WHO) was observed as liver dysfunction in 1 patient. Transarterial chemotherapy
      with SMANCS, which is well tolerated, appears to have moderate antitumor effect
      in patients with HCC.

PMID- 9663416
TI  - Mediastinal large cell lymphoma: prognostic significance of CT findings at
      presentation and after treatment.
AB  - OBJECTIVE: Primary mediastinal large cell lymphoma is a distinctive subtype of
      non-Hodgkin's lymphoma. Computed tomography (CT) has become an integral part of
      the evaluation of these patients at presentation and after completion of therapy.
      The purpose of this study is to identify CT features that predict increased risk
      of relapse. METHODS: A retrospective study of patients with primary mediastinal
      large cell lymphoma who underwent CT scans of the thorax. RESULTS: Tumor volume
      greater than 100 ml after completion of therapy was a statistically significant
      predictor of increased risk of relapse (p=0.02, Fisher exact test). Other
      measurements (obtained at presentation and after completion of treatment) were
      not statistically significant in predicting relapse. CONCLUSION: CT plays an
      important role in predicting outcome in primary mediastinal large cell lymphoma.
      Large residual tumor volume after completion of treatment predicts an increased
      risk of relapse.

PMID- 9663417
TI  - Colon cancers and peritoneal mesothelioma occurring 29 years after abdominal
      radiation for testicular seminoma. A case report and review of the literature.
AB  - Secondary malignancies represent an increasing problem for long survivors of
      primary malignancies treated by chemo- and/or radiotherapy. The occurrence of
      secondary myelodysplasia and leukaemias after treatment for Hodgkin's disease is
      well established. Secondary solid tumors are mostly observed following radiation
      therapy. We report the case of a patient who presented 3 abdominal solid
      malignancies within 3 years, 29 years after abdominal radiotherapy for a
      testicular seminoma, namely 2 colon cancers and a peritoneal mesothelioma. Both
      types of cancer are independently reported in the literature to be more frequent
      in patients with a history of abdominal radiation than in the general population.
      To our knowledge there is no other reported case with 3, nearly simultaneously
      occurring separate solid tumors, which could all be related to former abdominal
      irradiation. Such a radiotherapy-related long-term side effect should be taken
      into account when considering adjuvant radiotherapy in patients with low-risk
      stage I testicular seminoma.

PMID- 9663418
TI  - Does dexamethasone enhance the efficacy of alizapride in cis-platinum-induced
      delayed vomiting and nausea?
AB  - At the present time 5-HT3 antagonists in combination with corticosteroids
      represent the best prophylaxis and treatment of acute vomiting and nausea in
      highly emetogenic cancer chemotherapy. However, 24 h after chemotherapy 5-HT3
      antagonists are no longer superior to benzamides for prevention of delayed
      symptoms. All recommendations for use of corticosteroids in delayed nausea and
      vomiting basically rely on one small study by Kris et al. [J Clin Oncol
      1989;7:108-114]. Since the use of corticosteroids in cancer chemotherapy remains
      controversial, this single-blind, randomised, prospective trial was initiated to
      re-evaluate the benefits of corticosteroids during the days after chemotherapy.
      Thus patients treated for ovarian cancer received 5 mg tropisetron (Navoban) plus
      20 mg dexamethasone for the prevention of acute vomiting and nausea in cis
      platinum-containing chemotherapy (50 mg). Twenty-four hours after the beginning
      of chemotherapy 49 patients were randomised to receive 3 x 100 mg alizapride
      (Vergentan) plus a placebo medication (group A) and 47 patients to receive 3 x
      100 mg alizapride plus 3 x 4 mg dexamethasone (group B) for 3 days depending on
      the incidence of acute vomiting beginning on day 2. The well-being of both groups
      was compared using objective and subjective parameters (Rotterdam Symptom
      Checklist). Major control of acute vomiting was achieved in 87.5% of the cases.
      The study was stopped after this interim analysis of 96 patients revealed no
      advantage of corticosteroids during the days after chemotherapy. Significant
      differences between both groups were detected only on a few days (day 6:
      objective nausea in favour of group A, day 4: objective vomiting in favour of
      group B, day 6: objective vomiting in favour of group A, day 3: constipation in
      favour of group A, days 4 and 5: difficulty concentrating in favour of group A,
      day 3: dry mouth in favour of group B). In contrast to acute nausea and vomiting
      the addition of corticosteroids is not beneficial in the prevention of delayed
      nausea and vomiting. Until better strategies are available the best prophylaxis
      of delayed symptoms is the control of acute nausea and vomiting using 5-HT3
      antagonists plus corticosteroids. The use of benzamides has to be considered
      efficacious in the prevention of delayed vomiting and nausea.

PMID- 9663419
TI  - Prognostic value of DNA ploidy and proliferating cell nuclear antigen in gastric
      cancer.
AB  - DNA ploidy and the labeling index (LI) of proliferating cell nuclear antigen
      (PCNA) in gastric cancers were determined using cytofluorometry and
      immunohistochemistry, respectively, and the prognostic value of these two
      parameters was evaluated. Of 66 patients with advanced gastric cancers treated
      with radical resection, 27 with aneuploidy and a high PCNA-LI (> or = 40) showed
      the lowest 5-year survival rate (38%). Twenty patients with diploid cancers and a
      high LI showed a lower 5-year survival rate (59%) than the 15 patients with
      diploid cancers and a low LI (<40), who had the highest 5-year survival rate
      (86%). A multivariate analysis showed that the grouping based on the ploidy and
      the LI was an independent prognostic factor. Thus, the combination of DNA ploidy
      and PCNA-LI may be a useful prognostic indicator for advanced gastric cancers.

PMID- 9663420
TI  - Immunoreactive MUC1 expression at the deepest invasive portion correlates with
      prognosis of colorectal cancer.
AB  - This study sought to examine the relationship between MUC1 expression at the
      deepest invasive portion, invasive/metastatic potential, and prognosis of
      colorectal cancer in relation to cellular proliferation. MUC1 expression was
      detected immunohistochemically using KL-6 antibody (anti-MUC1 monoclonal
      antibody) in 100 surgically resected specimens of advanced colorectal cancer.
      Distinct staining of the luminal surfaces, defined as positive immunoreactive
      (IR)-MUC1 expression, was seen in more than 30% of the tumor cells at the deepest
      invasive portion. The proliferating cell nuclear antigen labeling index (PCNA-LI)
      was also examined in the same areas. IR-MUC1 expression was detected in 71 (71%)
      of 100 lesions. Lesions with lymphatic or venous invasion showed a significantly
      higher incidence of IR-MUC1 expression than those without lymphatic or venous
      invasion (80 vs. 42% and 82 vs. 61%, respectively). Lesions with lymph node
      metastasis showed a significantly higher incidence of IR-MUC1 expression than
      those without lymph node metastasis (88 vs. 53%). Lesions with liver metastasis
      showed a significantly higher incidence of IR-MUC1 expression than those without
      liver metastasis (92 vs. 59%). Dukes' stage was also significantly correlated
      with IR-MUC1 expression. The incidence of IR-MUC1 expression did not
      significantly differ with regard to histologic subclassification and depth of
      invasion. There was no significant correlation between IR-MUC1 expression and the
      PCNA-LI. IR-MUC1 expression at the deepest invasive portion revealed a
      significant correlation with prognosis; furthermore, in patients with better
      differentiated lesions, in those with lesions confined to muscularis propria or
      subserosa (subadventitial) invasion, in those with Dukes' B and C, or in those
      undergoing curative resection, IR-MUC1 expression significantly correlated with
      prognosis. Patients with high PCNA-LI lesions showed a significantly poorer
      prognosis than those with low PCNA-LI lesions. Only in patients undergoing
      curative resection, patients with IR-MUC1-positive and high PCNA-LI lesions
      showed a significantly poorer prognosis than those with IR-MUC1-negative and low
      PCNA-LI lesions. The significant risk factors in the order of poorer prognosis in
      patients undergoing curative resection by the multivariate analysis were the
      histologic grade (moderately-poorly, poorly or mucinous adenocarcinomas), IR-MUC1
      expression, and lymph node metastasis. These results indicate that IR-MUC1
      expression is an important predictor of the metastatic potential and the
      prognosis of colorectal cancer, independent of histologic grade, depth of
      invasion or cellular proliferative activity. Combined analysis of IR-MUC1 and
      histologic grade, and combined expression of IR-MUC1 and PCNA at the deepest
      invasive portion are especially useful in predicting colorectal cancer prognosis.

PMID- 9663421
TI  - Is continuous 24-hour infusion of 5-fluorouracil plus high-dose folinic acid
      effective in patients with progressive or recurrent colorectal cancer? A phase II
      study.
AB  - BACKGROUND: To evaluate the therapeutic activity of 24-hour continuously infused
      5-fluorouracil (5-FU) modulated by high-dose folinic acid in patients with
      metastatic colorectal cancer who had recurred or progressed following mainly
      bolus 5-FU/folinic acid chemotherapy. PATIENTS AND METHODS: Forty-two patients
      with a median age of 59 years (45-76) were enrolled. Karnofsky status was 90% (80
      100), previous chemotherapy regimen bolus 5-FU/folinic acid (n=33, 79%) or 24
      hour continuous 5-FU+/-interferon alpha2 (n=9, 21 %). Chemotherapy was given as a
      weekly infusion of 500 mg/m2 folinic acid over 2 h followed by a 24-hour
      continuous infusion of 2,600 mg/m2 5-FU for 6 consecutive weeks followed by a 2
      week rest period. RESULTS: No complete but 6 partial responses were observed
      (ORR: 14%, CI95%: 3.5-25.1%) with a median response duration of 7.3 months
      (range: 1.4-10.6). The median survival from the start of continuous infusion of 5
      FU was 11.6 months (range: 2-27, CI95%: 9.4-13.8) and the 1-year survival rate
      was 46%. Disease stabilization and minor responses were achieved in another 25
      patients (61%). WHO grade III/IV diarrhea occurred in 26% of patients, mucositis,
      nausea/vomiting and hand-foot syndrome in 5% each. Two cases of WHO grade III
      anemia and leukocytopenia were observed (5% each). Dose reductions had to be
      performed in 11 patients because of unacceptable diarrhea with subsequent stop of
      treatment in 2 patients. Progressive disease while receiving previous bolus 5-FU
      chemotherapy was associated with a lower response rate, shorter progression-free
      interval and overall survival compared to response and survival of patients who
      had achieved temporary disease stabilization during previous bolus 5-FU therapy.
      CONCLUSIONS: Continuous infusion of 5-FU/folinic acid displays activity in
      pretreated and refractory colorectal cancer with acceptable toxicity. Patients
      who had achieved disease stabilization or objective remission with previous 5-FU
      bolus therapy appear to be more likely to benefit from second-line treatment.
      Questions remaining to be addressed include the optimal starting dose of
      continuously infused 5-FU and whether the dose of folinic acid can be reduced or
      completely eliminated with respect to toxicity and health economics.

PMID- 9663422
TI  - Combined expression of HLA-DR antigen and proliferating cell nuclear antigen
      correlate with colorectal cancer prognosis.
AB  - HLA-DR antigen expression and the proliferating cell nuclear antigen labeling
      index (PCNA-LI) were examined immmunohistochemically in 59 surgically resected
      advanced colorectal cancers to clarify the clinicopathologic significance of the
      HLA-DR antigen. HLA-DR antigen expression was detected in 33 (56%) of the 59
      lesions, which showed less frequent liver metastasis than lesions without HLA-DR
      antigen expression (40 vs. 68%; p < 0.05). Five-year survival rates of patients
      with and without HLA-DR antigen expression were 50 and 19%, respectively. Lesions
      combining HLA-DR antigen expression and a relatively low PCNA-LI had the best
      prognosis. These results indicate that HLA-DR antigen expression, particularly
      combined with a low PCNA-LI, is an important outcome predictor in colorectal
      cancer.

PMID- 9663423
TI  - Mortality from cancer of the male reproductive tract and environmental exposure
      to the anti-androgen p,p'-dichlorodiphenyldichloroethylene in the United States.
AB  - The association of prostate cancer mortality and testicular cancer mortality with
      environmental exposure to the anti-androgen dichlorodiphenyltrichloroethane (DDT)
      derivative p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) in the USA was
      explored in the period 1971-1994 using multiple linear regression analysis.
      Environmental p,p'-DDE contamination by state was estimated by p,p'-DDE
      concentrations in the subcutaneous fat of population samples and by measurements
      of p,p'-DDE in tree bark. On average, African Americans had adipose p,p'-DDE
      levels 74% higher than Whites (8.49 vs. 4.88 microg/g; p < 0.001). Neither
      prostate cancer mortality nor testicular cancer mortality showed a positive
      association with either indicator of p,p'-DDE environmental contamination. On the
      contrary, the regression coefficient for prostate cancer was constantly inverse
      for adipose p,p'-DDE along the period of study, although it approached
      statistical significance only for African Americans in 1981-1985 (P=-0.755; 0.10
      > p > 0.05). This ecologic study does not provide support to the hypothesis of a
      link between environmental exposure to DDT derivatives and cancer of the male
      reproductive tract.

PMID- 9663424
TI  - Paclitaxel-induced cell-mediated hypersensitivity pneumonitis. Diagnosis using
      leukocyte migration test, bronchoalveolar lavage and transbronchial lung biopsy.
AB  - A 73-year-old man with mild inactive interstitial pneumonitis and non-small cell
      bronchogenic carcinoma developed a cell-mediated hypersensitivity pneumonitis
      within 15 days following a second exposure to paclitaxel. Histological features
      of transbronchial lung biopsy were consistent with interstitial pneumonitis.
      Bronchoalveolar lavage showed increased lymphocytes and eosinophils, and
      decreased helper/suppressor T lymphocyte ratio. Leukocyte migration inhibitory
      test was positive for paclitaxel. These results support the possibility that
      paclitaxel-induced pneumonitis is due to delayed type hypersensitivity; they also
      support the hypothesis of a central role of T lymphocytes in drug-induced
      pneumonitis.

PMID- 9663425
TI  - Pleural and bone marrow metastasis from supratentorial oligoastrocytoma grade
      III.
AB  - We report a 62-year-old man with symptomatic metastasis to the pleural cavity and
      the bone marrow from a supratentorial oligoastrocytoma grade III, 24 years after
      the initial symptoms. Before tumor dissemination, the patient underwent brain
      surgery four times in 5 years. Six months after the last treatment, extraneural
      dissemination to the right pleural cavity was discovered. Despite resection of
      the pleural metastasis, local and distant spread to the bone marrow developed.
      The patient died 5 months after the occurrence of extraneural tumor metastasis.
      It is speculated that repeated brain surgery and extended survival may promote
      extraneural dissemination of supratentorial oligoastrocytoma grade III.

PMID- 9663426
TI  - Curcumin inhibits SK-Hep-1 hepatocellular carcinoma cell invasion in vitro and
      suppresses matrix metalloproteinase-9 secretion.
AB  - Curcumin (diferuloylmethane), widely used as a spice and coloring agent in food,
      possesses potent antioxidant, anti-inflammatory and anticarcinogenic properties.
      Recently, curcumin was further demonstrated to have an antimetastatic effect in
      mice. In this study, we attempted to clarify the possible mechanisms of this
      latter effect of curcumin. A highly invasive SK-Hep-1 cell line of human
      hepatocellular carcinoma (HCC) was selected for this study. An in vitro assay,
      without or with Matrigel matrix, was used to quantitate cellular migration and
      invasion. Gelatin-based zymography was adapted to assay the secretion of matrix
      metalloproteinase (MMP). We found that curcumin, at 10 microM, inhibited 17.4 and
      70.6% of cellular migration and invasion of SK-Hep-1, respectively. Compared with
      a less invasive human HCC cell line, Huh-7, SK-Hep-1 showed a much higher MMP-9
      secretion. Further, and parallel with its anti-invasion activity, curcumin
      inhibited MMP-9 secretion in SK-Hep-1 in a dose-dependent fashion. We conclude
      that curcumin has a significant anti-invasion activity in SK-Hep-1 cells, and
      that this effect is associated with its inhibitory action on MMP-9 secretion.

PMID- 9663427
TI  - Effects of doxorubicin and/or cilostazol on cancer cells during liver
      regeneration after two-thirds hepatectomy in rats.
AB  - A rat model of liver metastases generated by intraportal injection of syngeneic
      tumor cells after two-thirds hepatectomy to determine the optimal benefit of
      doxorubicin and/or cilostazol for early hepatic metastases. Four groups of WKA
      rats had viable tumor cells injected directly into the portal vein after two
      thirds hepatectomy. Group A underwent to further treatment. Group B had
      doxorubicin injected 24 h post-operatively. Group C had cilostazol administered
      prior to two-thirds hepatectomy. Group D received cilostazol, and doxorubicin
      injections. The mean survival period in each group was 22.2, 20.0, 28.8, and 22.8
      days, respectively. The mean survival was significantly longer in group C than in
      groups A, B and D (p < 0.05). Based on these findings, we believe that during the
      phase of liver regeneration adjuvant chemotherapy is not recommended. Cilostazol
      exerts an important antiproliferative effect on liver metastases after
      hepatectomy.

PMID- 9663428
TI  - Expression of nm23-H1 gene and Sialyl Lewis X antigen in breast cancer.
AB  - The nm23 gene has been proposed as a candidate tumor metastasis suppressor in
      some human cancers. Sialyl Lewis X (sLex) has been demonstrated to play an
      important role in the adhesion of human cancer cells to human vascular
      endothelium, inducing metastasis. Little information has been reported about the
      correlation between the expression of nm23 and sialylated carbohydrate antigens.
      In the present study, 102 surgically resected primary breast cancer tissues were
      sectioned and stained with antibody against nm23-H1 and sLex. Of the 102 cases,
      39 (38.2%) cases with a reduced expression of nm23-H1 were observed, and the
      numbers of sLex-positive cases were 61 (59.8%), respectively. The reduced
      expression of nm23-H1 and the positive expression of sLex were significantly
      associated with lymph node involvement. Among the 100 patients who underwent
      curative surgery, the disease-free survival rate was significantly correlated to
      both the nm23-H1 and sLex expressions. No interrelated expressions were found
      between nm23-H1 and sLex. In multivariate analysis using Cox regression model,
      combination assay of nm23-H1 and sLex expression emerged as independent
      significant prognostic factors. These results suggest that nm23-H 1 gene and sLex
      may be involved in different steps of the metastatic process in human breast
      cancer, and immunohistochemical detection of the combination of sLex and nm23-H1
      may be a biologic marker of prognostic significance.

PMID- 9663429
TI  - Increased cyclin D1 in human pancreatic cancer is associated with decreased
      postoperative survival.
AB  - Cyclin D 1 belongs to a family of protein kinases that have been implicated in
      cell cycle regulation. In the present study we characterized cyclin D1 expression
      in 6 cultured human pancreatic cancer cell lines and in normal and cancerous
      human pancreatic tissues. A 4.4-kb cyclin D1 mRNA transcript was present in all
      cell lines and in all pancreatic tissues. Cyclin D1 mRNA levels were 2.1-fold
      higher in the pancreatic cancers than in normal pancreatic tissues (p < 0.0002).
      Cancer patients with lower cyclin D1 levels (n=16) had a median survival of 15.5
      months whereas patients with higher levels (n=16) had a median survival of 6.5
      months (p < 0.007). These data indicate that cyclin D1 expression may serve as a
      predictor of postoperative survival in pancreatic cancer patients, and raise the
      possibility that treatment modalities blocking cyclin D1 activity may have a
      future role in the therapy of these patients.

PMID- 9663430
TI  - Prognostic value of nm23 protein expression in renal cell carcinomas.
AB  - In the present study, an analysis of whether expression of nm23-H1 and nm23-H2
      proteins has prognostic significance was performed. A series of 95 renal cell
      carcinomas was analyzed for nuclear grade, tumor size (larger than 50 mm or not),
      staging in the Robson system and expression of nm23-H1 and nm23-H2, as well as
      patient survival. Immunohistochemical staining of nm23-H1 and nm23-H2 was found
      in 68.4 and 50.5% of the cases, respectively. Significant differences in nm23-H1,
      but not nm23-H2 expression were noted with regard to nuclear grade and tumor
      size. The patients with nm23-H1-expression-negative tumors sized < or = 50 mm had
      a significantly poorer prognosis than their positive counterparts. Multivariate
      analysis using the Cox proportional hazards regression model indicated that the
      staging in the Robson system and expression of nm23-H1 were significant and
      independent prognostic factors for survival. However, no significant correlation
      between the incidence of metastasis and expression of nm23-H1 or nm23-H2 was
      found. The results imply that reduced expression of nm23-H1 influences the
      prognosis of patients with renal cell carcinomas, but not the likelihood of
      metastasis. In small tumors sized < or = 50 mm, reduced expression of nm23-H1
      protein was suggested to be an especially strong predictor of a poor prognosis.

PMID- 9663431
TI  - Charlotte Schneyer: pioneer in salivary gland research.

PMID- 9663432
TI  - The epithelium-tooth interface--a basal lamina rich in laminin-5 and lacking
      other known laminin isoforms.
AB  - The attachment of the marginal gingiva to the tooth surface is mediated by a thin
      nonkeratinized epithelium termed the junctional epithelium (JE). Ultrastructural
      studies have revealed that the attachment of the JE to the tooth surface occurs
      through hemidesmosomes (HD) and a basal lamina-like extracellular matrix termed
      the internal basal lamina (IBL). We have previously shown that neither type IV
      collagen nor prototypic laminin, two common components of basement membranes
      (BM), is present in the IBL between the epithelium and the tooth. In the present
      study, we show that laminin-5 is a major component of the IBL in both rodent and
      human tissues. By using in situ hybridization, we also show that the cells of the
      JE express the LAMC2 gene of laminin-5. In other parts of gingival epithelium,
      LAMC2 gene expression is less prominent. Our results indicate that the epithelium
      tooth interface is a unique structure wherein epithelial cells are induced to
      secrete a basal lamina containing laminin-5 and no other presently known laminin
      isoform.

PMID- 9663433
TI  - A novel organ culture method to study the function of human odontoblasts in
      vitro: gelatinase expression by odontoblasts is differentially regulated by TGF
      beta1.
AB  - Odontoblasts cannot be cultured by traditional cell culture methods, thus
      restricting in vitro studies. Here we present an organ culture method for human
      odonto-blasts that utilizes the pulp chamber as a culture crucible. Crowns of
      human third molars were dissected, pulp was gently removed, and the odontoblasts
      attached to and in the walls of the pulp chambers were cultured in serum-free
      OPTI-MEM medium, or DMEM/Ham's F12 medium containing 10% serum. Pulp tissues were
      cultured separately. Cell content and morphology were analyzed by SEM, and the
      removed pulps were examined by light microscopy. Proteins secreted into the
      medium with or without TGF-beta1 supplementation were metabolically labeled with
      [35S]methionine, and the total protein content was assessed by TCA precipitation
      and SDS-PAGE/fluorography. To assess the role of gelatinolytic enzymes on dentin
      matrix remodeling, we used enzymography to analyze the effect of TGF-beta1 on
      gelatinase A and B expression. SEM revealed odontoblasts in pulp chambers after 5
      days of culture, with only few or no fibroblasts, and no alterations in the
      odontoblast cell morphology or differences between the cells cultured in serum
      free and serum-containing media. Rarely were any odontoblasts present in pulp
      tissue. Radiolabeling revealed protein synthesis and secretion until day 6 in
      both the odontoblast and pulp cultures, with no marked differences between TGF
      beta1-treated and control cultures. The level of gelatinase A remained constant
      up to 7 days, while gelatinase B expression was always low and decreased with
      time in culture. However, gelatinase B levels were markedly increased upon TGF
      beta1 treatment of cells and remained high to day 7. The results suggest that
      this method provides a novel technique for the study of human odontoblasts in
      vitro and that odontoblasts can be cultured even in serum-free conditions.

PMID- 9663434
TI  - HLA-DR alleles are associated with IDDM, but not with impaired neutrophil
      chemotaxis in IDDM.
AB  - Insulin-dependent diabetes mellitus (IDDM) is a risk factor for periodontitis.
      Depressed neutrophil chemotaxis has been demonstrated in IDDM and in early-onset
      periodontitis (EOP). HLA-DR antigens are associated with both IDDM and
      periodontitis. This investigation sought to determine an association of HLA-DR3, 
      DR4, and -DR53 with impaired neutrophil chemotaxis in an IDDM sample. The
      neutrophil chemotaxis index of 41 diabetics and 27 controls was determined by a
      modified Boyden chamber method, and certain class II HLA genotypes were
      determined by polymerase chain-reaction amplification of genomic DNA by means of
      sequence-specific primers (PCR-SSP). The mean chemotaxis index of the diabetics
      was significantly less than that of the controls (p < or = 0.02). HLA-DR3 (p < or
      = 0.002), -DR4 (p < 0.003), and -DR53 (p < or = 0.001) were associated with IDDM.
      Neutrophil chemotaxis and glucose metabolism were not significantly correlated.
      None of the HLA-DR alleles was associated with impaired neutrophil chemotaxis.
      Therefore, the neutrophil chemotaxis defect of IDDM appears to be independent of
      these HLA-DR-associated genes.

PMID- 9663435
TI  - Changes in the expression of extracellular matrix (ECM) and matrix
      metalloproteinases (MMP) of proliferating rat parotid acinar cells.
AB  - Tissue morphogenesis, development, and maintenance of function are mediated by
      signals generated through the composition of the extracellular matrix. The
      regulation of the composition of matrix is determined by enzymes specific for
      their degradation, the matrix metalloproteinases. Chronic injections of the beta
      adrenergic receptor agonist, isoproterenol, result in a non-neoplastic
      hypertrophy and hyperplasia of the rat parotid gland. The activity of matrix
      metalloproteinases, as measured by gelatin zymography and enzymatic digestion of
      Azocoll substrates by gland lysates, decreased significantly (P < 0.05) following
      24 hrs of agonist treatment, and slowly recovered to control values by 6 days of
      treatment. Daily administration of the broad-spectrum matrix metalloproteinase
      inhibitor Galardin for 3 days in combination with isoproterenol resulted in
      enhanced gland hypertrophy compared with that produced by isoproterenol alone.
      Given alone, Galardin also caused hypertrophy. The relative abundance of mRNA for
      the extracellular matrix molecules, collagens I and III and fibronectin, declined
      rapidly following the initiation of beta-agonist treatment in vivo, while laminin
      B1 and B2 mRNA levels increased initially before declining below control levels.
      These changes in patterns of mRNA levels also were observed in the concentrations
      of glandular protein when Western dot blot analysis of collagens I and III and
      laminin, respectively, was used. The importance of laminin, in vivo, was
      demonstrated by coinjection of anti-laminin antibody along with isoproterenol,
      which resulted in the inhibition of beta-agonist-induced parotid gland
      hypertrophy and hyperplasia. These data suggest that modulation of the ECM is
      associated with isoproterenol-induced salivary gland hypertrophy and hyperplasia.
      It is likely that this modulation of the ECM takes place through transcriptional
      regulation of some ECM genes and regulation of matrix-degrading enzyme activity.

PMID- 9663436
TI  - Submandibular salivary proteases: lack of a role in anti-HIV activity.
AB  - Whole human saliva contains a number of proteolytic enzymes, mostly derived from
      white blood cells and bacteria in the oral cavity. However, less information is
      available regarding proteases produced by salivary glands and present in salivary
      secretions. In the present study, we have analyzed submandibular saliva,
      collected without contaminating cells, and identified multiple proteolytic
      activities. These have been characterized in terms of their susceptibility to a
      series of protease inhibitors. The submandibular saliva proteases were shown to
      be sensitive to both serine and acidic protease inhibitors. We also used protease
      inhibitors to determine if salivary proteolytic activity was involved in the
      inhibition of HIV infectivity seen when the virus is incubated with human saliva.
      This anti-HIV activity has been reported to occur in whole saliva and in ductal
      saliva obtained from both the parotid and submandibular glands, with highest
      levels of activity present in the latter fluid. Protease inhibitors, at
      concentrations sufficient to block salivary proteolytic activity in an in vitro
      infectivity assay, did not block the anti-HIV effects of saliva, suggesting that
      the salivary proteases are not responsible for the inhibition of HIV-1
      infectivity.

PMID- 9663437
TI  - Proteoglycan expression in the rat temporomandibular joint in response to
      unilateral bite raise.
AB  - The vertebrate articular tissue consists of collagen fibers embedded in a ground
      substance. Collagen resists tensile forces, while proteoglycans in the ground
      substance provide resilience and resistance to compression. It was hypothesized
      that unilateral bite raise would induce increasing expression of proteoglycans in
      TMJ articular tissues. As a test of this hypothesis, six- and nine-week-old
      Sprague-Dawley rats received unilateral bite-raising appliances bonded to their
      right upper molars for 4 wks. A group of nine-week-old rats was housed for an
      additional 4 wks after removal of the appliances they had worn for 4 wks.
      Proteoglycans that carry abundant chondroitin sulfate and keratan sulfate side
      chains, most likely aggrecans, were detected by safranin O in the
      fibrocartilaginous zone of the condyle in parasagittal sections. A monoclonal
      antibody against a large chondroitin sulfate proteoglycan related to versican
      reacted strongly in the surface fibrous layer of the mandibular condyle and
      moderately in the discs of the treated specimens. Computer quantification for
      safranin O and anti-versican antibody staining revealed that the average
      intensities of the treated specimens were significantly higher than those of
      their corresponding sham-operated controls, and the average intensities of the
      treatment-reversal specimens had no significant differences from their
      corresponding sham-operated controls. Thus, unilateral bite raise appeared to
      have induced an increase in the expression of aggrecan in the condylar cartilage
      and a proteoglycan related to versican in the TMJ disc and the articular surface
      of the condyle. The elevated proteoglycan expression is interpreted to suggest
      that unilateral bite raise leads to an increase in the magnitude of compressive
      forces in the rat temporomandibular joint.

PMID- 9663438
TI  - Perceptions of the natural dentition in the context of multiple variables.
AB  - Perceived oral health status has been shown to be associated with a variety of
      single clinical and self-reported indicators of oral health and oral health
      related behaviors. A behavioral model is utilized which hypothesizes that
      perceived condition of natural teeth is predicted by multiple factors, including
      individual demographic and enabling characteristics, other health perceptions and
      orientations, actual levels of diseases and conditions, and self-defined need for
      treatment. The data are from the clinical examination and adult questionnaire of
      Phase 1 (1988-1991) of the Third National Health and Nutrition Examination
      Survey, which is based on a stratified multistage probability sample to produce
      nationally representative data for the civilian, non-institutionalized US
      population. Multivariate hierarchical regressions were used to assess perceived
      condition of natural teeth in two groups of dentate adults (those with a dental
      visit during the past 12 months, and those with a less recent dental visit). Self
      defined treatment need made a significant, non-trivial contribution after other
      variables had been controlled. In both subpopulation models, the perception of
      general health and epidemiological indicators of oral health status were also
      significant factors. Socio-economic indicators did not contribute significantly
      in either regression. Understanding components of overall perceptions of oral
      health moves us closer to understanding oral health behaviors and oral-health
      related quality of life.

PMID- 9663439
TI  - Automatic on-line one-channel recognition of masseter activity.
AB  - The etiology of myoarthropathies of the masticatory system (MAP) is not fully
      understood. For the hypothetical association between the myogenous pain of MAP
      patients and masticatory muscle overuse to be proved, functional and
      parafunctional behavior of the masticatory muscles should be analyzed in normal
      and diseased subjects. The aim of this study was to test on-line the validity and
      reliability of an algorithm, applied to the electromyographic signal, to
      recognize various oral activities. The surface electromyogram of the masseter
      muscle was recorded in 12 subjects (seven females and five males, from 18 to 32
      years old) who performed a series of functional and parafunctional activities
      (chewing soft food, chewing hard food, swallowing, laughing, speaking, and tooth
      grinding and clenching), as well as no activity. During the computer training
      phase, intra-individual classification functions of a multivariate discriminant
      analysis were calculated while each subject performed the described activities.
      During the test phase, each subject repeated the same activities, and the
      computer continuously classified them on-line. The percentage of correctly
      recognized activities was calculated for each activity and for each subject. No
      activity, chewing hard food, swallowing, laughing, grinding, and clenching were
      recognized correctly > 99% of the time. Chewing soft food was recognized
      correctly 97% and speaking 86% of the time. The sensitivity values for the
      recognition rates of the complete oral activities were, with one exception, >
      0.82; the specificity values were > 0.95, and the kappa-values > 0.80. These
      results show that the algorithm had high sensitivity, specificity, and
      reliability in the classification of different oral activities under laboratory
      conditions.

PMID- 9663440
TI  - The effects of xylitol-containing chewing gums on dental plaque and acidogenic
      potential.
AB  - The aim of this study was to test the hypothesis that the chewing of xylitol- or
      xylitol/sorbitol-containing chewing gum reduces plaque formation and the
      acidogenic potential of dental plaque. Thirty healthy volunteers aged from 19 to
      28 yrs were randomly allocated to one of three test groups, chewing either
      xylitol-, xylitol/sorbitol-, or sucrose-sweetened gums. A three-day plaque
      accumulation period of no oral hygiene was instituted prior to and at the
      termination of the chewing gum program, which lasted 33 days. Plaque quantity was
      assessed on the basis of protein content of individual plaque samples collected
      by a standardized technique. Acidogenic potential of individual baseline and test
      plaque samples was assessed by the quantity of various organic acids formed from
      D-(U-14C)glucose. Identification of extracellular and intracellular metabolites
      was performed by HPLC. Statistical evaluation of data was performed according to
      paired comparisons of individual baseline and post-chewing data. Plaque
      formation, acidogenic potential, and glycolytic profiles were similar at baseline
      and after the gum-chewing periods. Also, there was no intracellular accumulation
      of glycolytic metabolites within the plaque bacteria to indicate the inhibition
      of glycolysis. The study thus leads to the conclusion that, in young adults with
      low caries experience, exposure of the oral cavity to acceptable doses of xylitol
      or xylitol and sorbitol has no effect on the microbial deposits on the teeth.

PMID- 9663441
TI  - Chemical durability of Dicor and fluorocanasite-based glass-ceramics.
AB  - Fluorocanasite (Al2O3-CaO-F-K2O-Na2O-SiO2) glass-ceramics exhibit fracture
      toughness values of up to 5.0 MPa x m1/2. However, their chemical durability is
      not adequate for dental applications. The objective of this study was to test the
      hypothesis that an increased concentration of Al2O3 can increase the chemical
      durability of fluorocanasite-based glass-ceramics. Glass frits containing 2 wt%
      (CAN2), 5 wt% (CAN5), and 10 wt% Al2O3 (CAN10) were melted individually, poured
      into a graphite mold, and cut into 16-mm-diam. x 2-mm-thick disks. Each disk was
      crystallized at 850 degrees C for 6 hrs. The disks were immersed in a solution of
      de-ionized-distilled water, 4% acetic acid, or a pH 1 buffer solution, and sealed
      in 90-mL Teflon containers. Corrosion testing was performed by means of
      vibrational motion at 60 cycles per min in a shaker-bath at 80 degrees C for 15
      days. Solution analyses were performed by means of a pH meter, an atomic
      absorption spectrophotometer, and an inductively coupled plasma spectrometer.
      Samples exposed to 4% acetic acid solution exhibited a mean weight loss rate
      (WLR) for the control group (Dicor) of 0.04+/-0.01 mg/cm2 day, which was
      significantly lower (p < or = 0.0001) than the mean WLR of the CAN2 (1.08+/-0.02
      mg/cm2 x day), CAN5 (1.31+/-0.02 mg/cm2 x day), and CAN10(1.51+/-0.05 mg/cm2 x
      day) groups. The reduced durability of fluorocanasite-based glass-ceramics with
      increasing Al2O3 concentration is most likely associated with a more uniform
      distribution of smaller crystals during heat treatment of the glass.

PMID- 9663442
TI  - Mechanical properties of hydroxyapatite and OH-carbonated hydroxyapatite single
      crystals.
AB  - Single-crystal hydroxyapatite and OH-carbonated hydroxyapatite have bending
      strength much higher than that of dense hydroxyapatite ceramic, indicating
      potential applicability to a load-bearing biomaterial. However, the effects of
      carbonate on the strength are less clear. The objective of the present study was
      to determine the bending strength and Young's modulus of these single crystals
      with carbonate contents from 0 to 0.62 in CO2 wt%. Three-point bending tests were
      performed by means of a modified ultra-microhardness tester with a span of 380
      microm and a bending direction <210> of the single crystals. The crystals were
      broken in air, water, and air after immersion in a cell culture medium for 3 wks.
      The average Young's modulus of the single crystals was from 54 to 79 GPa. The
      average bending strength of the single crystals in air was 500+/-184, 468+/-205,
      513+/-151, and 450+/-162 MPa for those with 0, 0.09, 0.37, and 0.62 wt%
      carbonate, respectively. No significant decrease in strength was found for
      hydroxyapatite single crystals both in water and after the immersion in the
      medium. However, the strength of OH-carbonated hydroxyapatite single crystals
      decreased significantly by 23 to 43% in water in proportion to the carbonate
      content. The strength of single crystals with 0.37 and 0.62 wt% carbonate
      decreased significantly, even after the immersion in the medium. Therefore,
      hydroxyapatite single crystals are superior to OH-carbonated hydroxyapatite
      single crystals as a biomaterial for a load-bearing purpose.

PMID- 9663443
TI  - RK-2: a novel rabbit kidney defensin and its implications for renal host defense.
AB  - Defensins are endogenous antimicrobial peptides. We demonstrated recently the
      existence of RK-1, a defensin-like peptide in rabbit kidneys. Defining the renal
      defensin system is an essential step toward understanding how the kidney responds
      to infection. Here, using a combination of high-performance liquid
      chromatography, matrix-assisted laser desorption time-of-flight mass
      spectrometry, amino acid compositional analysis, and microsequence analysis, we
      show that the rabbit kidney contains a novel alpha-defensin-like peptide, RK-2.
      This work establishes the existence of a new subfamily of alpha-defensins in the
      kidney.

PMID- 9663444
TI  - Isolation of periviscerokinin-2 from the abdominal perisympathetic organs of the
      American cockroach, Periplaneta americana.
AB  - Using the isolated hyperneural muscle as bioassay, a novel myotropin was isolated
      from the abdominal perisympathetic organs of Periplaneta americana. This is the
      second neuropeptide identified from insect perisympathetic organs. Peptide
      sequence analysis and mass spectrometry yielded the following structure: Gly-Ser
      Ser-Ser-Gly-Leu-Ile-Ser-Met-Pro-Arg-Val-NH2. This peptide, named periviscerokinin
      2, was confirmed to be amidated by chemical synthesis, bioassay, and comparison
      of retention times between native and synthetic peptides. A highly specific
      antiserum was used to determine sites of synthesis in the abdominal ganglia.
      Besides periviscerokinin-1, periviscerokinin-2 is the only putative myotropic
      neurohormone from the abdominal perisympathetic organs that is effective in the
      nanomolar range. This confirms the hypothesis that the neurohormonal system of
      the ventral nerve cord is remarkably different from that of the brain.

PMID- 9663445
TI  - Melittin, a metabostatic peptide inhibiting Gs activity.
AB  - Some basic amphiphilic peptides are known to directly stimulate heterotrimeric
      GTP-binding proteins (G proteins). Mastoparan and melittin are known to stimulate
      Gi activities. Here, we found melittin inhibited guanine nucleotide-dependent
      adenylyl cyclase activity in synaptic membranes of the rat cerebral cortex.
      However, in insect cell membranes overexpressing specific heterotrimeric G
      proteins using baculovirus expression system, melittin showed unique effects
      different from those by mastoparan on G protein activities. This peptide markedly
      stimulated Gi1 and G11 activities, whereas it did inhibit Gs activities. Kinetic
      studies revealed that the inhibition of Gs activity by melittin is attributed to
      the inhibition of GDP release in exchange for added guanine nucleotides (or the
      association of guanine nucleotides). Thus, melittin may be the first metabostatic
      peptide inhibiting G protein (Gs) activity, and both mechanisms through the
      stimulation of Gi and inhibition of Gs might be involved in the melittin-induced
      inhibition of adenylyl cyclase.

PMID- 9663446
TI  - About 8-hour variation of circulating human endothelin-1.
AB  - Plasma endothelin-1 (ET-1) and cortisol were measured around the clock at hourly
      intervals on 7 clinically healthy, diurnally active, nocturnally resting subjects
      22-27 years of age. The circadian rhythm in cortisol is demonstrated for each
      subject (p < or = 0.020) as well as on a group basis (p = 0.002), peaking in the
      morning. By contrast, the circadian variation of ET-1 is statistically
      significant in only one of the subjects, and it is not detected for the group as
      a whole (p > 0.20). Instead, ET-1 is characterized by an about 8-h component (p <
      0.001) that is not found for cortisol.

PMID- 9663447
TI  - AVP rhythm in the suprachiasmatic nucleus in relation to locomotor activity under
      constant light.
AB  - To examine the roles of Arg-vasopressin (AVP)- and vasoactive intestinal peptide
      (VIP)-containing neurons in the suprachiasmatic nucleus (SCN) in production of
      circadian rhythmicity of locomotor activity, variations in the contents of AVP
      and VIP in punched-out SCN tissue and locomotor activity were measured under a
      light-dark cycle as well as under conditions of constant light for up to 3 weeks.
      Under the light-dark cycle, contents of AVP and VIP, and locomotor activity
      showed marked circadian rhythmicity. Under constant light, AVP content showed
      circadian rhythmicity until 3 weeks, while VIP rhythm disappeared from the first
      week with decreases in its content. Locomotor activity showed a free-running
      circadian rhythm for more than 3 weeks under constant light conditions in most
      cases. These results suggest that AVP but not VIP in the SCN may be involved in
      the generation of locomotor activity rhythm under conditions of constant light.

PMID- 9663448
TI  - Injection of oxytocin into the medial preoptic-anterior hypothalamus increases
      ultrasound production by female hamsters.
AB  - Recent studies of hamsters have documented the facilitation of lordosis and other
      sociosexual responses by injections of oxytocin (OXT) into the medial preoptic
      area-anterior hypothalamus (MPOA-AH). These data suggest the regulation of social
      interaction and bonds by OXT. In turn, this suggests that OXT could act in the
      MPOA-AH to control other behaviors involved in the initiation or maintenance of
      social contact, including the ultrasonic vocalizations that female hamsters use
      to alert and attract potential mates. To test this possibility, we compared the
      ultrasound rates of 11 naturally estrous hamsters before and after injections of
      OXT (200 ng/200 nl of saline) or saline (200 nl) into the MPOA-AH. The data
      revealed a clear facilitation of ultrasound rate 30 min after OXT treatment. This
      result suggests the modulation of ultrasound rate by endogenous OXT acting within
      the MPOA-AH. It extends the range of social behaviors sensitive to control by OXT
      and supports the possibility that OXT acts within the MPOA-AH to facilitate a
      variety of behaviors involved in the establishment or maintenance of the social
      interactions required for successful reproduction. At the same time, these data
      extend earlier observations linking ultrasound production to the MPOA-AH, and
      begin to describe the peptidergic mechanisms controlling this form of
      reproductive behavior.

PMID- 9663449
TI  - The octadecaneuropeptide ODN induces anxiety in rodents: possible involvement of
      a shorter biologically active fragment.
AB  - The octadecaneuropeptide ODN has been originally characterized as an endogenous
      ligand of central-type benzodiazepine receptors, on its ability to displace the
      anxiogenic compound beta-[3H]carboline-3-carboxylate methyl ester from its
      binding sites. The aim of the present study was to investigate the anxiogenic
      effects of intracerebroventricular administration of ODN in mice and rats. At
      doses ranging from 10 to 100 ng, ODN increased in mice the latency to explore a
      white compartment when the animals were placed in a black one. ODN also reduced
      the first stay duration in the white compartment. These effects were antagonized
      by diazepam (0.075 mg/kg, s.c.) as well as flumazenil (1 mg/kg, s.c.), indicating
      that ODN acts as an inverse agonist on central-type benzodiazepine receptors. In
      rats, ODN reduced the latency to enter a black compartment when the animals were
      placed in the white one. In the plus-maze elevated test, ODN reduced, in both
      mice and rats, the number of entries and the time spent in the open arm. In mice,
      ODN (100 ng) increased the thigmotaxis index, i.e. the distance traveled in the
      peripheral zone of the open field. Time-course studies revealed that a
      significant effect of ODN (100 ng) in the black/white compartment test was only
      observed 40 min after the injection and lasted between 3 and 6 h. The effect of a
      1000-ng dose of ODN appeared more tardily than that of a 10-ng dose. In addition,
      a 1000-ng dose of ODN occluded the early effect of a 100-ng dose on the white
      compartment first stay duration. The COOH-terminal octapeptide of ODN was more
      rapidly effective than ODN in the black/white compartment test, suggesting that
      the anxiogenic effect of the peptide requires the formation of biologically
      active proteolytic fragment.

PMID- 9663450
TI  - Sulfated cholecystokinin (26-33) induces mild taste aversion conditioning in rats
      when administered by three different routes.
AB  - We investigated the ability of sulfated cholecystokinin (26-33) (CCK-8) and
      cholecystokinin (30-33) (CCK-4) to induce taste aversion or avoidance
      conditioning (TAC) in a one-bottle testing paradigm after either intravenous
      (i.v.), intracerebroventricular (i.c.v.), or intraperitoneal (i.p.)
      administration. Significant TAC was induced by i.p. administration of CCK-8 at
      0.1 but not at 0.025, 0.5, or 1.0 micromol/kg; the TAC was not robust and, in
      this case, not even dose related. I.p. administration of CCK-4 at 0.05, 0.1, 0.5,
      or 1.0 micromol/kg did not induce TAC, replicating other studies from our lab.
      Mild but significant TAC was also induced by i.v. administration of CCK-8 (at
      0.025 and 1.0 but not 0.1 or 0.5 micromol/kg) but not by i.v. administration of
      CCK-4 (at 0.05, 0.1, 0.5, or 1.0 micromol/kg). Finally, mild but significant TAC
      was induced by i.c.v. (i.e., lateral ventricular) administration of CCK-8 (at
      0.0015 but not at 0.015 micromol/brain) but not by i.c.v. administration of CCK-4
      (at 0.005 or 0.010 micromol/brain). Because CCK-4 failed to induce TAC, CCK-8
      apparently induced TAC via all three routes by an action at a CCK(a), not CCK(B),
      receptor mechanism. Because i.c.v. or i.v. administrations of CCK-8 were not more
      efficacious than i.p. administration, the taste avoidance induced by i.p.
      administration of CCK-8 was not so mild simply because it failed to reach a
      critical central locus adequately or because it failed to be delivered at a
      critical speed (i.e., via i.v. injections). We demonstrate that CCK-8 can induce
      mild TAC at either peripheral or central sites and suggest that these effects of
      CCK-8 may be independent and may be a sign of salience but not necessarily of
      toxicosis.

PMID- 9663451
TI  - Cholecystokinergic innervation of nucleus accumbens subregions.
AB  - Behavioral and pharmacological evidence has shown a different and opposite role
      of the neuropeptide cholecystokinin (CCK) on the dopamine (DA) function in the
      caudal versus rostral part of the nucleus accumbens. Previous reports have
      speculated that the caudal region of the nucleus accumbens would receive CCKergic
      innervation from dopaminergic neurons of the mesencephalic ventral tegmental
      area, whereas the CCKergic input to the rostral accumbens would originate in non
      dopaminergic neurons from extra-mesencephalic areas of the brain. In the present
      study, this issue was addressed using retrograde tracing techniques in
      conjunction with immunocytochemistry. Retrograde tracers were injected in the
      three compartments of the accumbens (i.e., rostral pole, core and septal shell).
      In summary, our results demonstrate that 1) the main CCKergic input of the
      accumbens originates in the ventral mesencephalon; 2) the rostral pole is equally
      innervated by CCK neurons projecting from both substantia nigra pars compacta and
      ventral tegmental area; 3) the primary source of CCK innervation of the accumbal
      core is the substantia nigra pars compacta; and 4) whereas the CCKergic input to
      the septal shell originates primarily in the ventral tegmental area.
      Additionally, our results also showed that most of the CCKergic neurons
      projecting to any of the accumbal compartments also produce dopamine. These data
      constitute the first neuroanatomical evidence for the differential effects of CCK
      on dopamine actions in the different regions of the nucleus accumbens.

PMID- 9663452
TI  - Differential effects of intracerebroventricular glucagon-like peptide-1 on
      feeding and energy expenditure regulation.
AB  - Intracerebroventricular (i.c.v.) administration of glucagon-like peptide-1-(7-37)
      amide (GLP-1) has been shown to modulate food and water intake. The present
      studies further characterize the effects of i.c.v. GLP-1 in the regulation of
      energy balance in lean and obese animals. In both obese and lean Zucker rats, a
      single i.c.v. infusion of GLP-1 (1-30 microg) resulted in a dose-dependent
      reduction of food intake and decrease in respiratory quotient relative to the
      saline control during the first 2 h of the nocturnal cycle. In obese Zucker rats,
      the food intake was reduced by 73 +/- 11% of the control at the 30 microg dose,
      whereas a modest 45 +/- 18% reduction was observed in lean rats. Despite the
      large reduction in food intake seen with GLP-1, there was no compensatory
      decrease in nocturnal oxygen consumption in the obese Zucker rats. Interestingly,
      low doses of GLP-1 (1 microg) in lean Zucker rats, which had minimal effects on
      food intake, caused a 19 +/- 7% increase in O2 consumption during the first 2 h
      of the nocturnal cycle. These data suggest that central GLP-1 may be an important
      factor controlling negative energy balance in both the lean and obese Zucker
      rats.

PMID- 9663453
TI  - The inhibitory effect of glucagon-like peptide-1 (7-36)amide on antral motility
      is antagonized by its N-terminally truncated primary metabolite GLP-1 (9
      36)amide.
AB  - In plasma, glucagon-like peptide-1 7-36 amide (GLP-1) is rapidly degraded from
      the N terminus, generating the endogenous metabolite GLP-1 9-36 amide. This
      cleavage of GLP-1 eliminates its incretin effect, and the metabolite even may act
      as an antagonist. We have shown previously that GLP-1 strongly inhibited cephalic
      induced antral motility in pigs. We decided, therefore, to examine the effect of
      GLP-1 9-36 amide, with and without GLP-1, on cephalic-induced motility in pigs.
      In one series of experiments, we studied the effect of three different doses of
      GLP-1 9-36 amide (2, 4, and 10 pmol/kg/min) on insulin-induced (hypoglycemia)
      antral motility in anaesthetized pigs (n = 9). In another series, we studied the
      effect of infusion of GLP-1 9-36 amide in two different doses (1 and 5
      pmol/kg/min) in six pigs in which the antral motility was inhibited by GLP-1 7-36
      amide in a dose of 2 pmol/kg/min. Plasma levels of intact GLP-1 7-36 amide and
      GLP-1 9-36 amide were determined using specific radioimmunoassays. Insulin
      induced hypoglycemia increased the antral motility index from 0.4 +/- 0.1 to 8.3
      +/- 3.5 (cm/min). The motility was constant throughout the experimental period
      and was absolutely unaffected by the infusion of GLP-1 9-36 amide at 10
      pmol/kg/min, which resulted in a plasma concentration of 351 +/- 60 pmol/l. The
      inhibitory effect of GLP-1 7-36 amide on antral motility was reduced from 93 +/-
      3% to 33 +/- 9% (p < 0.05) by concomitant infusion of GLP-1 9-36 amide in a dose
      of 5 pmol/kg/min. The metabolite GLP-1 9-36 amide has no effect on antral
      motility in pigs but is able to antagonize the inhibitory effect of GLP-1. Thus,
      an intact N terminus is essential for the gastrointestinal actions of GLP-1. Its
      primary metabolite may act as an endogenous antagonist.

PMID- 9663454
TI  - Differential permeability of the blood-brain barrier to two pancreatic peptides:
      insulin and amylin.
AB  - Insulin and amylin are cosecreted by pancreatic B cells and have receptors within
      the central nervous system (CNS), where they exert multiple effects. Although
      these peptides are not produced in the CNS, their ability to cross the blood
      brain barrier (BBB) explains their presence there. We used multiple-time
      regression analysis to measure, in mice, the unidirectional influx constant (Ki)
      of each of these peptides to compare their rates of transport with each other and
      in different regions of the brain. The uptake of amylin by whole brain and by the
      cerebellum, midbrain, frontal cortex, parietal cortex, and occipital cortex was
      greater than that for insulin. For amylin, the areas of highest uptake were the
      pons-medulla and the cerebellum, and the areas of lowest uptake were the thalamus
      and midbrain. For insulin, the areas of highest uptake were the pons-medulla and
      the hypothalamus, whereas three regions (midbrain, thalamus, and occipital
      cortex) did not have a measurable Ki. The peak percent of injected dose taken up
      by whole brain was 0.12% for amylin and 0.046% for insulin. These results show
      that the permeabilities of these two peptides across the BBB differed from each
      other and among brain regions, suggesting that differential permeability of the
      BBB for blood-borne peptides could provide a mechanism by which their effects on
      the CNS are regulated.

PMID- 9663455
TI  - Galanin stimulates glucocorticoid secretion in rats through a receptor-dependent
      activation of the adenylate cyclase/protein kinase A-dependent signaling pathway.
AB  - Galanin, a 29-amino acid peptide widely distributed in the central and peripheral
      nervous systems, was found to induce a concentration-dependent increase in
      corticosterone secretion and cyclic-AMP release by dispersed rat inner
      adrenocortical cells (maximal effective concentration, 10(-7) M). The effect of
      10(-7) M galanin was blocked by 10(-6) M galantide, a specific antagonist of
      galanin receptors. Galanin (10(-7) M) also enhanced corticosterone and cyclic-AMP
      responses of dispersed cells to submaximal but not maximal (10(-9) M) effective
      concentrations of ACTH, and again this effect was reversed by galantide. The ACTH
      receptor antagonist corticotropin-inhibiting peptide (10(-6) M) blocked
      corticosterone response of dispersed cells to 10(-9) M ACTH but not to 10(-7) M
      galanin; conversely, the specific protein kinase A inhibitor H-89 (10(-5) M)
      annulled the secretory response to both ACTH and galanin. In light of these
      findings, we conclude that galanin stimulates adrenal glucocorticoid secretion in
      rats, acting through specific receptors, coupled, like those of ACTH, with the
      adenylate cyclase/protein kinase A-dependent signaling pathway.

PMID- 9663456
TI  - Sensitivity of brain sites to the inhibitory effect on alcohol intake of the
      tachykinin aminosenktide.
AB  - The present study evaluated the sensitivity of several brain sites to the
      inhibitory effect of the tachykinin (TK) NK-3 receptor agonist aminosenktide (NH2
      SENK) on 10% ethanol intake in genetically selected Marchigian Sardinian alcohol
      preferring rats. Attention was focused on limbic structures involved in alcohol
      seeking behavior and endowed with TK NK-3 receptors. NH2-SENK was bilaterally
      injected into the shell of the nucleus accumbens (NACC), the medial amygdala
      (AMY), the dorsal hippocampus (HIPP), the ventral tegmental area (VTA), the bed
      nucleus of the stria terminalis (BNST), the lateral hypothalamus (LH), and the
      nucleus basalis magnocellularis (NBM). NH2-SENK (injected up to 25-75 ng/site)
      into the NACC, AMY, HIPP, and VTA did not significantly modify ethanol intake.
      Injection of NH2-SENK into the BNST reduced ethanol intake at doses of 25 ng/site
      or higher, but the same doses also reduced water intake in water-deprived rats
      and food intake in food-deprived rats. Injection of NH2-SENK into the LH or the
      NBM at doses of 0.5, 5, or 25 ng/site inhibited 10% ethanol intake even at the
      lowest dose tested without affecting either food or water consumption in deprived
      animals. Present results indicate that the LH and the NBM are highly sensitive to
      the inhibitory effect of the TK NK-3 receptor agonist NH2-SENK on ethanol intake.
      TK peptides have been shown to evoke conditioned place preference following
      injection in the LH or the NBM, suggesting that in these brain sites the effect
      of TK agonists on ethanol intake might be due to interference with reward
      processes.

PMID- 9663457
TI  - Cleavage of atrial natriuretic peptide by a kidney membrane-bound
      carboxypeptidase A.
AB  - An enzymatic activity that cleaved the C-terminal Tyr of ANP (1-28) was
      characterized in human kidney microvillar membranes by using 125I-labeled rat ANP
      as substrate. This activity was inhibited by potato carboxypeptidase inhibitor
      (PCI) and 1.10 phenanthroline, suggesting that it corresponded to a metallo
      carboxypeptidase. Solubilization experiments indicated that the carboxypeptidase
      activity could be recovered in the supernatant after 1% Triton X-100 extraction.
      As separation by ion exchange chromatography revealed several peaks of enzyme
      activity, PCI coupled to Sepharose was used for purification. This step resulted
      in a single protein band at 30 kDa, as analyzed by SDS-PAGE.

PMID- 9663458
TI  - Immunocytochemical distribution of neurokinin 1 receptor in rat dorsal vagal
      complex.
AB  - Gastric adaptive relaxation is a vago-vagal reflex, probably involving the site
      of interface of vagal afferents and efferents in the dorsal vagal complex of the
      medulla. Previous studies have shown that both substance P and nitric oxide in
      the dorsal vagal complex decrease intragastric pressure. The purpose of this
      study is, firstly, to localize NK1 tachykinin receptor immunoreactive (ir)
      staining in the dorsal vagal complex and, secondly, to determine its anatomical
      relationship to nitrergic cells in the dorsal motor nucleus of the vagus.
      Sections were stained by avidin-biotin immunocytochemistry using antiserum to NK1
      receptor alone or combined with NADPH-diaphorase histochemistry. In the nucleus
      tractus solitarius, NK1 receptor-ir varicosities were moderately dense in the
      medial subnucleus, but sparse in the centralis and gelatinosus subnuclei. In the
      dorsal motor nucleus of the vagus, NK1 receptor-ir staining in cell bodies and
      fibers was present throughout, with a markedly dense varicose fiber and cell body
      staining in a lateral column of the rostral portion of the nucleus. NADPH
      diaphorase staining is most marked in cell bodies in the same region of the
      dorsal motor nucleus of the vagus. In dual-stained sections, there was complete
      overlap of NADPH-diaphorase and NK1 receptor-ir stain; however, the markers were
      very rarely colocalized within the same vagal motor neurons. Ipsilateral vagotomy
      almost completely abolished NK1r-ir staining in vagal motor neurons. We conclude
      that, in the dorsal motor nucleus of the vagus, NK1 receptor is synthesized by a
      population of vagal motor neurons which are in close anatomical proximity to, but
      separate from, nitrergic neurons. Based on these observations, substance P
      mediated gastric relaxation in this region is unlikely to be via activation of
      nitrergic vagal preganglionic neurons. In the nucleus tractus solitarius, the NK1
      receptor and NADPH-diaphorase stain are not codistributed in subnuclei mediating
      gastric and esophageal control. Therefore, substance P and nitric oxide may
      mediate their respective gastrointestinal effects via separate afferent pathways.

PMID- 9663459
TI  - Endomorphin 1 and 2 have vasodepressor activity in the anesthetized mouse.
AB  - The endogenous peptides endomorphin 1 and 2 are newly discovered, potent,
      selective mu-opioid receptor agonists. In the present study, we investigated
      responses to the endomorphin peptides in the systemic vascular bed of the
      anesthetized mouse. Endomorphin 1 and 2 induced dose-related decreases in mean
      arterial pressure when injected in doses of 3-100 nmol/kg i.v. Mean arterial
      pressure decreased 14 +/- 4, 23 +/- 4, and 42 +/- 5 mm Hg at the 10, 30, and 100
      nmol/kg doses, respectively, of endomorphin 1 (n = 5-7; p < 0.05), and similar
      changes were observed in response to endomorphin 2. In terms of relative
      vasodepressor activity, endomorphin 1 and 2 were about equipotent and about
      threefold more potent than the mu-opioid selective agonist PL017 in decreasing
      mean arterial pressure; all three peptides decreased heart rate. The time-course
      of the vasodepressor responses to endomorphin 1 and 2 were similar in rate of
      onset and decay. Vasodepressor responses to endomorphin 1 and 2 and PL017 but not
      to nociceptin were inhibited by the opioid receptor antagonist naloxone in a dose
      of 2 mg/kg i.v. When compared in the mouse and rat, the relative decreases in
      systemic arterial pressure in response to i.v. injections of endomorphin 1 and 2
      did not differ greatly. However, the duration of the vasodepressor response was
      significantly longer in the rat. These results demonstrate that endomorphin 1 and
      2 have significant, naloxone-sensitive, vasodepressor activity in the mouse.

PMID- 9663460
TI  - Characterization of [125I]beta-endorphin binding sites in the rat caudal
      dorsomedial medulla.
AB  - [125I]beta-endorphin bound to high affinity (Kd = 0.25 nM) receptors in the
      caudal dorsomedial medulla of rats with a Bmax of 97 fmol/mg protein. The
      relative potency for displacement of [125I]beta-endorphin binding was: beta
      endorphin(1-31) > beta-endorphin(1-27) > DAMGO > naloxone > N-acetyl-beta
      endorphin(1-31) > U50488 > DPDPE. The Bmax for [3H]DAMGO binding was 81 fmol/mg
      protein, indicating that most [125I]beta-endorphin binding corresponds to mu
      opioid receptors. [3H]DAMGO binding was not influenced by lesioning noradrenergic
      nerve terminals in the caudal dorsomedial medulla. Our findings indicate that
      beta-endorphin interacts primarily with mu-opioid receptors in the caudal
      dorsomedial medulla. These receptors are not affected by noradrenergic
      denervation.

PMID- 9663461
TI  - Detection of pro-opiomelanocortin mRNA in human and rat caudal medulla by RT-PCR.
AB  - Pro-opiomelanocortin (POMC) mRNA has been localized in the NTS of the rat, but
      not in the human or other species. Here, we report that RT-PCR amplification of
      human caudal medulla RNA generated a distinct band on agarose gels corresponding
      in size and sequence to the predicted 742-bp POMC PCR product. The 742-bp signal
      was undetectable following amplification of cortex, amygdala or caudate nucleus
      RNA. An homologous, 678-bp band was amplified from rat caudal medulla and,
      unexpectedly, from other brain regions. Competitive RT-PCR demonstrated that POMC
      cDNA from rat cortex, striatum and cerebellum was 17%, 22% and 45% of caudal
      medulla levels. These data indicate that the POMC gene is expressed in human
      caudal medulla and suggest that small amounts of POMC mRNA are present in regions
      other than the hypothalamus and NTS of rat brain.

PMID- 9663462
TI  - Role of tachykinins in the regulation of the hypothalamo-pituitary-adrenal axis.
AB  - Tachykinins are a family of neuropeptides, which act by binding to three main
      subtypes of G protein-coupled receptors, named NK1, NK2 and NK3. Tachykinins are
      contained in both nerve fibers and secretory cells of the hypothalamo-pituitary
      adrenal (HPA) axis, and evidence indicates that they take part in the functional
      control of it. Tachykinins involved in this function include substance P (SP),
      neuropeptide K and its derivative neurokinin A (NKA), and neurokinin B, which
      preferentially bind to NK1, NK2 and NK3 receptors, respectively. NK1 agonists
      exert an inhibitory effect on the hypothalamo pituitary CRH/ACTH system, while
      NK2 and perhaps NK3 agonists stimulate it, thereby controlling the secretion and
      growth of the adrenal cortex via circulating ACTH. Intra-adrenal tachykinins may
      also affect the cortex function. Their direct action on adrenocortical cells is
      doubtful and probably pharmacologic in nature, but several investigations suggest
      that tachykinins indirectly stimulate the cortex by acting on medullary
      chromaffin cells, which in turn exert a paracrine control on adrenocortical
      cells. SP enhances aldosterone production of zona glomerulosa by eliciting
      catecholamine secretion; neuropeptide K and NKA raise glucocorticoid production
      of zonae fasciculata and reticularis through the activation of the intramedullary
      CRH/ACTH system. The relevance of these effects of tachykinins under basal
      conditions is questionable, although there are indications that SP is involved in
      the maintenance of a normal growth and steroidogenic capacity of rat zona
      glomerulosa, and that SP and NKA play an important role in the stimulation of the
      adrenal growth during the fetal life. In contrast, evidence has been provided
      that the role of tachykinins, and especially of SP, could become very relevant
      under paraphysiological (e.g., physical or inflammatory stresses) or pathological
      conditions (e.g., ACTH-secreting pituitary tumors), when an excess of steroid
      hormone production has to be counteracted.

PMID- 9663463
TI  - Human CUL-1, but not other cullin family members, selectively interacts with SKP1
      to form a complex with SKP2 and cyclin A.
AB  - The budding yeast gene product, CDC53p, forms E3-like SCF complexes with SKP1 and
      F-box-containing proteins to mediate the ubiquitin-dependent degradation of G1
      cyclins and cyclin-dependent kinase (CDK) inhibitors. Cdc53 represents a
      multigene family, the human homologues of which, the cullin family, include at
      least six distinct members. We have found that human cullin 1, but not the other
      closely related cullins 2, 3, 4A, and 5, selectively interacts with human SKP1.
      This CUL1-SKP1 interaction is mediated by the NH2-terminal domains of both
      proteins, and the association appears to be required for the interaction of CUL1
      with SKP2, an essential element of the S-phase cyclin A-CDK2 kinase. In an
      asynchronous population of dividing cells, a minor amount of CUL1 specifically
      associates with cyclin A but not with other cyclins or CDK inhibitors. The steady
      state levels of both CUL1 and SKP1 as well as their association with one another
      remain relatively constant throughout the cell cycle and in postmitotic cells.
      Our findings indicate that the SCF pathway, although similarly used by the
      mammalian cullin 1, is not shared by other cullin members. This implies that most
      cullins may use a SKP1/F-box-independent pathway to facilitate protein
      degradation.

PMID- 9663464
TI  - Dynamic expression and activation of ERBB receptors in the developing mouse
      mammary gland.
AB  - The complex system of ERBB receptors and ligands is implicated in growth and
      differentiation of the mammary gland. However, it has not been comprehensively
      examined in this dynamic tissue. Combined RNA and protein analyses of glands in
      different stages from virgin to involution revealed differential expression of
      the four ERBB receptors, as well as distinctive patterns of ERBB ligand
      expression that suggested specialized function. ERBB localization was linked to
      mammary gland function. Thus, in the virgin gland, ERBB1 and ERBB2 were
      colocalized to all major cell types during ductal morphogenesis but
      differentially localized in the mature gland. All four ERBB receptors were
      restricted to epithelia in the differentiated gland. Analyses of ERBB tyrosine
      phosphorylation provided strong evidence of interaction between the four
      receptors in this physiological context. Thus, exogenous EGF induced stage
      dependent transphosphorylation of ERBB2-4 as well as ERBB1, whereas endogenous
      phosphorylation of all four receptors peaked in late pregnancy and lactation.

PMID- 9663465
TI  - Butyrate-induced G1 arrest results from p21-independent disruption of
      retinoblastoma protein-mediated signals.
AB  - When treated with millimolar concentrations of butyrate, many cell types undergo
      growth arrest in the G1 phase of the cell cycle. However, the molecular basis of
      butyrate-induced G1 arrest has not been elucidated. We have investigated the
      molecular mechanisms of butyrate-induced G1 arrest in synchronized cultures of
      untransformed 3T3 fibroblasts. We tested the hypothesis that butyrate-induced
      growth arrest might be mediated by the p21 cyclin-dependent kinase inhibitor.
      Sodium butyrate-treated 3T3 cells did, indeed, express elevated levels of p21
      mRNA under conditions of G1 arrest. Surprisingly, however, primary cultures of
      fibroblasts from transgenic p21 "knockout" (p21-/-) mice and fibroblasts from
      wild-type p21-proficient (p21+/+) mice underwent butyrate-induced G1 arrest with
      similar dose dependencies. Therefore, p21 expression was not necessary for
      butyrate-induced G1 arrest. To identify other potential mechanisms of butyrate
      induced growth arrest, we analyzed the butyrate sensitivity of key mitogenic
      signaling events during G1. We found that butyrate inhibited the mitogen
      dependent transcriptional induction of cyclin D1 and phosphorylation of
      retinoblastoma (Rb), both in p21-proficient 3T3 cells and in p21+/+ and p21-/-
      mouse embryo fibroblasts. Butyrate treatment also prevented mitogen-dependent
      transcriptional induction of cyclin E and expression of cyclin A, cell cycle
      events that are temporally distal to expression of cyclin D and are necessary for
      entry into S phase. Abrogation of a requirement for cyclin D/cyclin-dependent
      kinase-dependent phosphorylation of Rb (by ectopic expression of the human
      papilloma virus E7 oncoprotein in 3T3 cells) resulted in decreased sensitivity to
      the antiproliferative actions of butyrate. Overall, these data show that butyrate
      induced G1 arrest is, in large part, independent of p21 induction. Instead,
      butyrate-induced growth arrest appears to result from perturbation of the Rb
      signaling axis at the level of or at a stage prior to cyclin D1 expression.

PMID- 9663466
TI  - Overexpression of CC10 modifies neoplastic potential in lung cancer cells.
AB  - CC10 is infrequently expressed in non-small cell lung cancer cell lines, despite
      being abundantly produced by progenitor cells for normal and neoplastic airway
      epithelium. We overexpressed CC10 cDNA in the non-small cell lung cancer cell
      line A549 to determine its effect on the neoplastic phenotype. A549 cells
      transfected with CC10 demonstrated a marked reduction in invasiveness that was
      paralleled by diminished 92-kDa and absent 72-kDa metalloproteinase activity by
      zymography. Western analysis revealed the near absence of the corresponding
      matrix metalloproteinases (MMPs) MMP-2 and MMP-9 in the CC10-transfected cell
      lines, but not in the vector-transfected cell lines. The CC10-transfected cell
      lines also demonstrated decreased adhesiveness to fibronectin compared with the
      controls. CC10 expression was associated with decreased anchorage-independent
      growth but not with decreased anchorage-dependent growth. These data suggest that
      loss of CC10 may contribute to carcinogenesis, because CC10 antagonizes the
      neoplastic phenotype.

PMID- 9663467
TI  - Thrombopoietin supports in vitro erythroid differentiation via its specific
      receptor c-Mpl in a human leukemia cell line.
AB  - Thrombopoietin (TPO) acts on megakaryopoiesis and erythropoiesis in vitro and in
      vivo. We isolated a novel subline, UT-7/GMT, from the human leukemia cell line UT
      7/GM (N. Komatsu, et al., Blood, 89: 4021-4033, 1997). A small population of UT
      7/GM cells positively stained for hemoglobin (Hb) after a 7-day exposure to TPO.
      More than 50% of TPO-treated UT-7/GMT cells positively stained for Hb. Using UT
      7/GMT cells, we examined how TPO promotes hemoglobinization. TPO induced tyrosine
      phosphorylation of the TPO receptor but not the erythropoietin (EPO) receptor.
      There was no competition between TPO and EPO for binding to EPO receptor. These
      findings suggest that TPO has a direct effect on hemoglobinization via a specific
      receptor on UT-7/GMT cells. Isoelectric focusing demonstrated that TPO induced
      fetal and adult Hb synthesis, whereas EPO induced embryonic, fetal, and adult Hb
      synthesis. Thus, our data suggest that TPO has a distinct action on
      erythropoiesis.

PMID- 9663468
TI  - Inhibition of MCF-7ras tumor growth by carboxymethyl benzylamide dextran:
      blockage of the paracrine effect and receptor binding of transforming growth
      factor beta1 and platelet-derived growth factor-BB.
AB  - The highly tumorigenic human breast cancer MCF-7ras line (Ha-ras-transfected MCF
      7 cell line) loses estrogen dependence and secretes diffusible growth factors
      that support its own tumor growth in vivo. Our previous studies showed that
      carboxymethyl benzylamide dextran (CMDB7) inhibits the growth of breast MCF-7 and
      MCF-7ras cell lines. In this study, we have shown that conditioned medium (CM)
      from MCF-7 and MCF-7ras cells stimulated the DNA synthesis of BALB/c3T3
      fibroblasts and that CMDB7 strongly inhibited these mitogenic effects in a dose
      dependent manner. Neutralizing antibodies against platelet-derived growth factor
      (PDGF) partially inhibited the mitogenic effect of MCF-7ras CM. The flow
      cytometry analysis of the cell cycle showed that the CM of tumor cells increased
      the percentage of fibroblasts in S phase and that CMDB7 blocked them in G0/G1
      phase. CMDB7 inhibited the mitogenic effect of PDGF-BB and transforming growth
      factor (TGF) beta1 but not those of epidermal growth factors and insulin-like
      growth factor on BALB/c3T3 fibroblasts. CMDB7 increased the electrophoretic
      mobility of radiolabeled PDGF-BB and TGF-beta1, apparently by forming a stable
      complex with these factors. On intact BALB/c3T3 fibroblasts, binding of iodinated
      growth factors (125I-TGF-beta1 and 125I-PDGF) to their receptors was completely
      displaced by CMDB7. In vivo studies demonstrated that s.c. injection of CMDB7
      inhibited by 66% the tumor growth of MCF-7ras xenografts in nude mice. These
      results showed that CMDB7 inhibits the mitogenic effect of growth factors
      released from MCF-7 and MCF-7ras cells and suppresses tumor growth in the MCF
      7ras model.

PMID- 9663469
TI  - The role of nitric oxide in inflammation and immunity.

PMID- 9663470
TI  - Posttranslational protein modifications, apoptosis, and the bypass of tolerance
      to autoantigens.

PMID- 9663471
TI  - Systemic lupus erythematosus in three ethnic groups: I. The effects of HLA class
      II, C4, and CR1 alleles, socioeconomic factors, and ethnicity at disease onset.
      LUMINA Study Group. Lupus in minority populations, nature versus nurture.
AB  - OBJECTIVE: To study the relative impact of immunogenetic versus socioeconomic
      factors on systemic lupus erythematosus (SLE) at disease onset/presentation.
      METHODS: Medical records regarding SLE onset/ presentation were abstracted on 229
      SLE patients who were enrolled in a prospective lupus outcome study. Patients
      were grouped in equivalent proportions of Caucasians, African Americans, and
      Hispanics. HLA-DRB1, DQA1, and DQB1 oligotyping, as well as C4 and CR1
      allotyping, were carried out by standard methods. In addition to these genetic
      factors, data on ethnicity, age at SLE onset, monthly income, level of education,
      and home ownership were entered into stepwise logistic or stepwise multiple
      linear regression models as independent variables, and each specific clinical
      feature (neurologic, renal, and cardiovascular disease due to SLE), as well as
      the total Systemic Lupus Activity Measure (SLAM) score and physician's global
      assessment of disease activity at disease onset, were entered as dependent
      variables. RESULTS: HLA-DRB1*0301 (DR3), DRB1*1503 (DR2), and DRB1*08 (DR8)
      alleles were more frequently found in Caucasians, African Americans, and
      Hispanics, respectively. Hispanics were more likely to have cardiac and renal
      disease, as well as a higher physician's global assessment of disease activity.
      African Americans were more likely to have neurologic disease, renal disease, and
      a higher SLAM score. Those with less education had a higher SLAM score. Patients
      with HLA-DRB1*01 had less renal disease and a lower SLAM score. Those with C4A*3
      alleles had a higher SLAM score and a higher physician's global assessment of
      disease activity. CONCLUSION: Both genetic and socioeconomic determinants, as
      well as other factors associated with Hispanic and African-American ethnicity,
      affect the presentation of SLE.

PMID- 9663472
TI  - Systemic lupus erythematosus in three ethnic groups: II. Features predictive of
      disease activity early in its course. LUMINA Study Group. Lupus in minority
      populations, nature versus nurture.
AB  - OBJECTIVE: To determine the factors associated with disease activity in patients
      with recent-onset (< or =5 years) systemic lupus erythematosus (SLE) who were of
      Hispanic, African-American, or Caucasian ethnicity. METHODS: Incident and
      prevalent cases of SLE, as defined by the American College of Rheumatology
      criteria for SLE, among the 3 ethnic groups were identified in Alabama (The
      University of Alabama at Birmingham) and Texas (The University of Texas-Houston
      Health Science Center and The University of Texas Medical Branch at Galveston).
      Variables from the sociodemographic, clinical, immunologic, immunogenetic,
      behavioral, and psychological domains were obtained using validated instruments.
      Disease activity was ascertained with the Systemic Lupus Activity Measure (SLAM).
      Stepwise domain regressions with SLAM score as the dependent variable were
      performed. Final ethnic-specific and overall regression models were obtained by
      entering variables that were retained in the domain regressions. RESULTS: SLAM
      scores at study entry were higher in the African Americans (mean +/- SD 12.6 +/-
      6.9) and Hispanics (11.0 +/- 6.2) than in the Caucasians (8.5 +/- 3.7) (P < or =
      0.001). The final overall regression model (R2 = 28%) for higher SLAM score
      included the following variables: African-American ethnicity, lack of private
      health insurance, abrupt disease onset, presence of anti-Ro antibodies, absence
      of HLA-DRB1*0301, higher levels of helplessness, and abnormal illness-related
      behaviors. CONCLUSION: Socioeconomic, immunologic, immunogenetic, behavioral, and
      psychological variables were all predictive of disease activity early in the
      course of SLE, irrespective of ethnic group. However, there remain ethnic group
      differences in disease activity that were not explained by these factors.

PMID- 9663473
TI  - Fcgamma receptor IIa polymorphism in Caucasian patients with systemic lupus
      erythematosus: association with clinical symptoms.
AB  - OBJECTIVE: The class II human leukocyte Fcy receptor for IgG (FcgammaRIIa) occurs
      in 2 codominantly expressed allelic forms (R131 and H131). Cells expressing IIa
      H131 interact much more effectively with complexed IgG2 and IgG3 than do cells
      with IIa-R131. This might be linked to variability in immune complex handling,
      and therefore related to disease pathogenesis. The present study examines these
      possibilities in a cohort of Caucasian patients with systemic lupus erythematosus
      (SLE). METHODS: One hundred eight Caucasian patients were diagnosed with SLE
      according to the American College of Rheumatology criteria. The SLE patients and
      187 Caucasian controls were genotyped for the FcgammaRIIa polymorphism, and
      associations between FcgammaRIIa genotypes, selected HLA haplotypes, and clinical
      as well as laboratory features were analyzed. RESULTS: No significant skewing of
      the FcgammaRIIa polymorphism was observed in the SLE cohort. Various clinical and
      serologic parameters were found more frequently or at a younger age in patients
      homozygous for the genotype IIa-R/R131 compared with those with the genotype IIa
      H/H131. In patients with the genotype IIa-R/R131, significantly higher
      frequencies of proteinuria, hemolytic anemia, anti-nuclear RNP antibodies, and
      hypocomplementemia were found. The only clinical symptom observed more frequently
      in patients homozygous for IIa-H/H131 was livedo. Patients with the IIa-R/R131
      genotype were significantly younger at disease onset and had an earlier incidence
      of arthritis, sicca syndrome, nephritis, lymphadenitis, hematologic
      abnormalities, immunologic abnormalities, lupus anticoagulant, cryoglobulinemia,
      and hypocomplementemia. HLA-DR3 was found in 41.7% of SLE patients, but was not
      associated with clinical symptoms, serologic abnormalities, or the homozygous
      genotypes of the FcgammaRIIa, although an association with a significantly later
      onset of SLE was found. CONCLUSION: The FcgammaRIIa polymorphism constitutes an
      additional factor that might influence the clinical manifestations and course of
      SLE, but does not represent a genetic risk factor for the occurrence of SLE.

PMID- 9663474
TI  - Clinical and radiographic outcomes of rheumatoid arthritis patients not treated
      with disease-modifying drugs.
AB  - OBJECTIVE: To compare the radiographic and clinical features of rheumatoid
      arthritis (RA) patients who were not given disease-modifying antirheumatic drugs
      (DMARDs) with those of RA patients who were followed up and treated with DMARDs
      at a rheumatology clinic. METHODS: The population of this case-control study
      includes a series of RA patients who immigrated to Israel from the previous Union
      of Soviet Socialist Republics and who were treated only with nonsteroidal
      antiinflammatory drugs. Control patients who were followed up and treated with
      DMARDs at our rheumatology clinic were matched by sex, disease duration, number
      of actively inflamed joints, and the presence of serum rheumatoid factor. The
      outcome measures were the number of deformed and radiographically damaged joints.
      Radiographic damage was evaluated by the methods of Steinbrocker and Sharp.
      RESULTS: The study population consisted of 22 RA patients (15 women, 7 men) who
      were not treated with DMARDs and 22 patients (15 women, 7 men) who were treated
      with DMARDs. The mean disease duration was 16.2 years for the study patients and
      14.3 years for the controls. Compared with the matched controls, RA patients who
      were not treated with DMARDs were found to have a significantly higher mean
      number of deformed joints (13.8 versus 7.2), a higher mean number of damaged
      joints (24.4 versus 15.5), and a higher overall damage score by the Sharp
      criteria (146.1 versus 65.7). CONCLUSION: RA patients who were not given DMARDs
      had a 1.57-fold increased number of radiographically damaged joints and a 2.22
      fold increased overall Sharp damage score compared with patients who were treated
      with second-line agents.

PMID- 9663475
TI  - Subclinical peripheral nerve involvement in patients with rheumatoid arthritis.
AB  - OBJECTIVE: Clinical involvement of the peripheral nervous system is uncommon in
      rheumatoid arthritis (RA); the most common disorders are multiple mononeuritis,
      sensorimotor neuropathy, and entrapment neuropathy. This study was undertaken to
      investigate the occurrence of electrophysiologically evident peripheral nerve
      involvement in RA patients without a clinical history of peripheral nerve
      involvement. METHODS: Forty RA patients were examined neurologically and
      electrophysiologically, and sural nerve biopsies were performed in 4. RESULTS: No
      patient reported symptoms or signs of peripheral nerve involvement. Twenty-six
      patients (65%) exhibited electrophysiologic findings consistent with a
      sensorimotor neuropathy (in 2 of them a carpal tunnel syndrome was also present),
      while 3 patients showed isolated carpal tunnel syndrome. There was a moderate
      loss of myelinated fibers in 3 of the 4 nerve biopsy samples, and all showed an
      increased number of endo- and perineurial vessels and some signs of axonal
      degeneration. CONCLUSION: Patients with RA may have electrophysiologic and
      histologic findings of peripheral nerve damage, even in the absence of clinical
      evidence of peripheral nerve involvement.

PMID- 9663476
TI  - Changes in biochemical markers of joint tissue metabolism in a randomized
      controlled trial of glucocorticoid in early rheumatoid arthritis.
AB  - OBJECTIVE: To determine the effects of low-dose prednisolone on joint tissue
      metabolism in early rheumatoid arthritis (RA). METHODS: In addition to a range of
      biochemical markers of cartilage, bone and synovial tissue turnover, levels of
      pro-matrix metalloproteinase 3 (pro-MMP-3), pro-MMP-1, and cytidine deaminase
      (CD) were measured in serum from 79 of 128 patients with early RA who took part
      in the Arthritis and Rheumatism Council Low-Dose Glucocorticoid Study. Serum
      concentrations of joint tissue metabolites on treatment and off treatment were
      compared using Student's t-test. RESULTS: Levels of the keratan sulfate epitope,
      5D4, and glycosaminoglycan (GAG) were similar on and off treatment. However, the
      levels of synovium-derived markers, hyaluronate (HA) and N-propeptide of type III
      procollagen (PIIINP), were reduced by 23.9% (P < 0.01) and 25.2% (P < 0.001),
      respectively, during treatment with prednisolone. Serum osteocalcin (OC) was
      reduced by 25.8% (P < 0.001), while the levels of CD and pro-MMP-3 increased by
      31.2% (P < 0.01) and 53.7% (P < 0.001) during prednisolone treatment compared
      with the off-treatment period. CONCLUSION: Low-dose prednisolone had no
      significant effect on markers of cartilage turnover (GAG, 5D4) in early RA,
      suggesting that early erosions do not involve cartilage surfaces. The reduction
      in the markers of bone turnover (OC) and synovial tissue turnover (HA and PIIINP)
      support the general view that prednisolone reduces synovitis and suppresses bone
      turnover.

PMID- 9663477
TI  - Intraarticular corticosteroid injection in the management of children with
      chronic arthritis.
AB  - OBJECTIVE: Intraarticular (IA) corticosteroid injection is a common therapeutic
      approach in the management of adult rheumatoid arthritis. This study examined the
      safety and efficacy of IA corticosteroid injection in 71 patients with juvenile
      arthritis who were being seen at the Sheba Medical Center during the years 1991
      1996. METHODS: Sixty-one patients fulfilled the American College of Rheumatology
      revised criteria for the diagnosis of juvenile rheumatoid arthritis (JRA), 6
      patients had reactive arthritis, and 4 patients had various other arthritic
      conditions. The mean +/- SD age was 9.4 +/- 5.6 years (range 0.5-18 years); 47
      were female (mean age 8.1 +/- 5.5 years) and 24 were male (mean age 10.8 +/- 5.4
      years). A total of 300 joints were injected with triamcinolone hexacetonide. The
      most common sites of injection were the knees (124 injections), ankles (71
      injections), wrists (46 injections), shoulders (10 injections), and elbows (7
      injections). Children under the age of 6 (n = 17), or older children who received
      more than 4 joint injections at one time (n = 10) were sedated with either
      ketamine HCI or propofol. All other children received their joint injections
      under local anesthesia. RESULTS: Full remission of the joint inflammation lasting
      >6 months following injection was achieved in 246 of the 300 injections (82.0%).
      In 54 (18.0%) of the injected joints, the inflammation recurred within 6 months
      of injection. In patients with pauciarticular arthritis, 115 of 141 injections
      (81.6%) resulted in full remission. Discontinuation of all oral medications was
      accomplished in 43 patients (60.6%) of the total group of 71 patients and in 32
      of the 43 patients with pauciarticular disease (74.4%). Correction of joint
      contraction was achieved in 42 children (55 joints). In all 11 patients with
      Baker's cyst and in 12 patients with tenosynovitis, complete remission was
      achieved following injection. No infection or other serious complications
      occurred in any of the patients following the procedure. CONCLUSION: IA
      corticosteroid joint injection in children with juvenile arthritis is a safe and
      effective mode of therapy. It may be the only therapy needed in patients with
      pauciarticular JRA, obviating the need for prolonged oral medications, and is
      effective in correcting joint contractions and deformities.

PMID- 9663478
TI  - Intravenous pulse cyclophosphamide in the treatment of interstitial lung disease
      due to collagen vascular diseases.
AB  - OBJECTIVE: Substantial toxicity limits the use of daily oral cyclophosphamide
      (CYC) for the treatment of interstitial lung disease (ILD) due to collagen
      vascular diseases. We examined whether intravenous (i.v.) pulse CYC can be
      substituted for daily oral therapy. METHODS: Six patients with rapidly
      progressive ILD due to polymyositis, systemic sclerosis, systemic lupus
      erythematosus, or primary Sjogren's syndrome received 6-9 cycles of i.v. pulse
      CYC (0.5 gm/m2 of body surface area), together with an initial course of 50 mg of
      prednisolone, which was tapered to a maintenance dosage of 5-7.5 mg/day, and
      their response was measured clinically, by high-resolution computed tomography
      (HRCT) and by assessment of the bronchoalveolar lavage (BAL) cell profile.
      RESULTS: All patients showed significant improvement in exercise tolerance and
      lung function. Elevated BAL neutrophils dropped substantially, whereas the
      response of BAL lymphocytes was inconsistent. Low-attenuation opacities in the
      HRCT regressed in 4 patients and remained unchanged in 2, but reticular
      infiltrates remained largely unaffected. Remission was maintained with
      hydroxychloroquine, azathioprine, or cyclosporin A. CONCLUSION: I.v. pulse CYC
      proved to be an effective and well-tolerated treatment in these patients. Since
      it appears to target mainly the inflammatory component of the disease, it should
      be reserved for progressive ILD featuring indices of high inflammatory activity.

PMID- 9663479
TI  - Distal musculoskeletal manifestations in polymyalgia rheumatica: a prospective
      followup study.
AB  - OBJECTIVE: To determine the frequency and the characteristics of distal
      musculoskeletal manifestations in polymyalgia rheumatica (PMR). METHODS:
      Prospective followup study of 177 consecutive patients meeting clinical criteria
      for PMR, diagnosed over a 5-year period in 2 rheumatology secondary referral
      centers in Italy. RESULTS: Seventy-nine of the 177 patients (45%) had distal
      musculoskeletal manifestations. Peripheral arthritis occurred in 45 patients
      (25%), carpal tunnel syndrome in 24 (14%), distal extremity swelling with pitting
      edema in 21 (12%), and distal tenosynovitis in 5 (3%). These manifestations were
      usually associated with PMR proximal symptoms (69%); however, 31% of the episodes
      represented isolated relapse/recurrence at distal sites. Distal symptoms
      responded promptly to corticosteroids. No evidence of joint deformities,
      erosions, or development of rheumatoid arthritis was observed during the
      followup. The group of patients with peripheral arthritis included a higher
      proportion of females, had a longer duration of therapy, and had more relapses/
      recurrences. Patients who had distal extremity swelling with pitting edema had a
      higher age at disease onset, a shorter duration of therapy, and lower initial and
      cumulative prednisone doses. CONCLUSION: Inflammatory involvement of distal
      articular and/or tenosynovial structures occurs in approximately half of the
      cases of PMR. Peripheral arthritis is associated with more severe disease, while
      distal extremity swelling with pitting edema appears to identify a more benign
      disease subset.

PMID- 9663480
TI  - Familial aggregation of osteoarthritis: data from the Baltimore Longitudinal
      Study on Aging.
AB  - OBJECTIVE: To evaluate the familial aggregation of osteoarthritis (OA) in a
      cohort of healthy volunteers drawn from a community setting. METHODS: Hand
      radiographs obtained between 1978 and 1991 and bilateral standing knee
      radiographs obtained between 1984 and 1991 were read for changes of OA, using
      Kellgren-Lawrence (K-L) scales. The hand sites were distal interphalangeal (DIP)
      joints, proximal interphalangeal (PIP) joints, and first carpometacarpal (CMC1)
      joints. For each joint group, the presence of OA in at least 1 joint in a joint
      group, the number of affected digits in each joint group, and the sum of the K-L
      grade across all joints were analyzed. Polyarticular OA was recorded if there
      were OA findings in 2 of 3 hand joint groups plus 1 or both knees. Data from 167
      families with hand radiographs, 157 families with knee radiographs, and 148
      families with both hand and knee radiographs were analyzed for sib-sib
      correlations. RESULTS: After adjustment for age, sex, and body mass index,
      clinically relevant sib-sib common correlations were found for OA of the DIP,
      PIP, and CMC1 joints, for OA at 2 or 3 hand sites, and for polyarticular OA (r =
      0.33-0.81) when OA was defined according to the number of affected joints or as
      the sum of the K-L grade across all joints. CONCLUSION: These results from a
      cohort of volunteers drawn from a community setting and ascertained without
      regard to OA status demonstrate familial aggregation of OA and contribute to the
      evidence for heritability of OA.

PMID- 9663481
TI  - Knee adduction moment, serum hyaluronan level, and disease severity in medial
      tibiofemoral osteoarthritis.
AB  - OBJECTIVE: The adduction moment at the knee during gait is the primary
      determinant of medial-to-lateral load distribution. If the adduction moment
      contributes to progression of osteoarthritis (OA), then patients with advanced
      medial tibiofemoral OA should have higher adduction moments. The present study
      was undertaken to investigate the hypothesis that the adduction moment normalized
      for weight and height is associated with medial tibiofemoral OA disease severity
      after controlling for age, sex, and pain level, and to examine the correlation of
      serum hyaluronan (HA) level with disease severity and with the adduction moment
      in a subset of patients. METHODS: Fifty-four patients with medial tibiofemoral OA
      underwent gait analysis and radiographic evaluation. Disease severity was
      assessed using the Kellgren-Lawrence (K-L) grade and medial joint space width. In
      a subset of 23 patients with available sera, HA was quantified by sandwich enzyme
      linked immunosorbent assay. Pearson correlations, a random effects model, and
      multivariate regression models were used. RESULTS: The adduction moment
      correlated with the K-L grade in the left and right knees (r = 0.68 and r = 0.60,
      respectively), and with joint space width in the left and right knees (r = -0.45
      and r = -0.47, respectively). The relationship persisted after controlling for
      age, sex, and severity of pain. The partial correlation between K-L grade and
      adduction moment was 0.71 in the left knees and 0.61 in the right knees. For
      every 1.0-unit increase in adduction moment, there was a 0.63-mm decrease in
      joint space width. In the subset of patients in whom serum HA levels were
      measured, HA levels correlated with medial joint space width (r = -0.55), but not
      with the adduction moment. CONCLUSION: There is a significant relationship
      between the adduction moment and OA disease severity. Serum HA levels correlate
      with joint space width but not with the adduction moment. Longitudinal studies
      will be necessary to determine the contribution of the adduction moment, and its
      contribution in conjunction with metabolic markers, to progression of medial
      tibiofemoral OA.

PMID- 9663482
TI  - Impaired phagocytosis of apoptotic cell material by monocyte-derived macrophages
      from patients with systemic lupus erythematosus.
AB  - OBJECTIVE: To investigate whether the established impaired phagocyte function in
      systemic lupus erythematosus (SLE) patients also affects apoptotic cell
      clearance. Accumulation of apoptotic waste as a source for autoantigens that
      induce and maintain autoimmune responses is discussed. METHODS: Apoptosis was
      detected by morphology and propidium iodide staining. In vitro phagocytosis of
      autologous apoptotic cells in cultured peripheral blood mononuclear cells was
      evaluated microscopically. Cross-feeding experiments were performed to
      investigate phagocytosis of heterologous apoptotic cells by in vitro
      differentiated macrophages. Furthermore, the effect of annexin V on the
      phagocytosis of apoptotic cells was investigated. RESULTS: Reduced clearance of
      apoptotic cells in SLE patients was observed. The defective clearance appeared to
      reflect phagocyte dysfunction and not an abnormal execution of apoptosis. A
      similar picture was seen when in vitro-differentiated macrophages from control
      populations were treated with annexin V. CONCLUSION: Noninflammatory engulfment
      phagocytosis of apoptotic cells is decreased in SLE patients. Persistently
      circulating apoptotic waste may encounter inflammatory removal pathways and serve
      as immunogen for the induction of autoreactive lymphocytes and as antigen for
      immune complex formation.

PMID- 9663483
TI  - Potential withdrawal of rheumatoid synovium by the induction of apoptosis using a
      novel in vivo model of rheumatoid arthritis.
AB  - OBJECTIVE: To investigate whether Fas-mediated apoptosis has potential as a new
      therapeutic strategy in rheumatoid arthritis (RA) by use of a novel model of RA
      in which human RA tissue is grafted into SCID mice. METHODS: Fresh rheumatoid
      synovial tissue including joint cartilage was grafted subcutaneously into the
      backs of SCID mice. Six weeks after engraftment, anti-Fas monoclonal antibody was
      injected intraperitoneally. Time-related apoptotic changes caused by anti-Fas
      monoclonal antibody in grafted synovium were evaluated by nick end-labeling
      histochemistry. RESULTS: Thirty-six hours after the injection, diffuse apoptotic
      changes were observed in the grafted synovia. Four weeks after the injection,
      rheumatoid synovial tissue diminished. CONCLUSION: This is the first report
      concerning the present effectiveness of anti-Fas monoclonal antibody in
      diminishing rheumatoid synovium in vivo, and suggests the possibility of a new
      strategy for treating rheumatoid arthritis by inducing Fas-mediated apoptosis.

PMID- 9663484
TI  - Modulation of angiogenic vascular endothelial growth factor by tumor necrosis
      factor alpha and interleukin-1 in rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the regulation of expression of the angiogenic cytokine
      vascular endothelial growth factor (VEGF) in rheumatoid arthritis (RA), in order
      to determine whether new blood vessel formation could be a potential therapeutic
      target in RA. METHODS: Dissociated RA synovial membrane cells were cultured in
      the presence of cytokine inhibitors, or under hypoxic conditions. Serum VEGF
      levels were serially measured in RA patients enrolled in clinical trials of anti
      tumor necrosis factor alpha (anti-TNFalpha) monoclonal antibody treatment.
      RESULTS: Combined neutralization of TNFalpha and interleukin-1 (IL-1) in RA
      synovial membrane cultures reduced VEGF release by 45% (P < 0.05 versus control),
      although blockade of either TNFalpha or IL-1 activities alone resulted in only
      small inhibitory effects. In addition, release of VEGF from RA synovial membrane
      cells was selectively up-regulated by hypoxia. Serum VEGF levels were
      significantly elevated in RA patients relative to control subjects, and
      correlated with disease activity. Treatment of RA patients with anti-TNFalpha
      significantly decreased serum VEGF, and this effect was enhanced by cotreatment
      with methotrexate. CONCLUSION: Inhibition of TNFalpha and IL-1 activity in vivo
      could reduce the drive to new blood vessel formation, and hence pannus mass,
      adding to other therapeutic effects of anti-TNFalpha therapy in RA.

PMID- 9663485
TI  - Chondrocyte apoptosis and nitric oxide production during experimentally induced
      osteoarthritis.
AB  - OBJECTIVE: Chondrocytes produce nitric oxide (NO) and undergo apoptosis in
      response to exogenous NO. This study sought to examine the relationship between
      NO synthesis, chondrocyte apoptosis, and the development of cartilage degradation
      during experimental osteoarthritis (OA). METHODS: OA was induced in rabbits by
      anterior cruciate ligament transection (ACLT). Knees were harvested after 4 weeks
      and assessed for OA severity and chondrocyte apoptosis. Conditioned media from
      cultured cartilage explants were analyzed for nitrite content. Cartilage sections
      were analyzed by immunohistochemistry for the presence of nitrotyrosine. RESULTS:
      All ACLT knees demonstrated osteoarthritic changes. Conditioned media from ACLT
      cartilage organ cultures contained higher levels of nitrite as compared with
      cartilage samples from the nonoperated side or from rabbits that had not received
      ACLT. Cultures of specific areas of cartilage from ACLT knees showed high levels
      of NO production in the medial femoral and medial tibial cartilage. Approximately
      28.7% of chondrocytes isolated from ACLT cartilage and 6.7% of chondrocytes from
      cartilage of the nonoperated side underwent apoptosis. In situ staining
      demonstrated apoptotic cells in the superficial and middle zones of ACLT
      cartilage. A high number of apoptotic cells was present at the pannus-cartilage
      junction. In control cartilage, the superficial zone contained a small number of
      cells in apoptosis. The prevalence of apoptotic cells was significantly
      correlated with the levels of nitrite production and OA grade. CONCLUSION: These
      observations suggest that, during the early phases of OA, NO production may lead
      to chondrocyte apoptosis, and that both events contribute to the pathogenesis of
      cartilage degradation. Inhibitors of NO synthesis and chondrocyte apoptosis may
      therefore be of therapeutic value after cartilage injury and in patients with OA.

PMID- 9663486
TI  - Reduced progression of experimental osteoarthritis in vivo by selective
      inhibition of inducible nitric oxide synthase.
AB  - OBJECTIVE: To evaluate the in vivo therapeutic efficacy of N-iminoethyl-L-lysine
      (L-NIL), a selective inhibitor of inducible nitric oxide synthase (iNOS), on the
      progression of lesions in an experimental osteoarthritis (OA) dog model. The
      effect of L-NIL on metalloprotease activity, levels of interleukin-1beta (IL
      1beta), prostaglandin E2 (PGE2), and nitrite/nitrate in synovial fluid was
      determined. METHODS: The OA model was created by sectioning the anterior cruciate
      ligament of the right stifle joint of mongrel dogs by a stab wound. Dogs were
      separated into experimental groups: Group 1 was made up of unoperated dogs that
      received no treatment, group 2 were operated dogs with no treatment, and group 3
      were operated dogs that received oral L-NIL (10 mg/kg/twice daily) starting
      immediately after surgery. The OA dogs were killed at 10 weeks after surgery.
      RESULTS: Experiments showed that dog OA cartilage explants in culture produced an
      increased amount of NO (nitrite). Immunohistochemical study demonstrated that
      this was due to an increased level of iNOS in chondrocytes. OA dogs treated with
      L-NIL showed a reduction in the incidence of osteophytes compared with the
      untreated OA dogs (58% versus 92%) as well as in their size (mean +/- SEM 1.92 +/
      0.58 mm versus 5.08 +/- 0.66 mm). Macroscopically, L-NIL decreased the size of
      the cartilage lesions by approximately 50% both on condyles and plateaus. The
      histologic severity of both the cartilage lesions and synovial inflammation was
      significantly decreased in the L-NIL-treated dogs. Treatment with L-NIL also
      significantly decreased both collagenase and general metalloprotease activity in
      the cartilage and the levels of IL-1beta, PGE2, and nitrite/nitrate in synovial
      fluid. CONCLUSION: This study demonstrated the effectiveness of a selective
      inhibitor of iNOS, L-NIL, in attenuating the progression of experimental OA. The
      data suggest that L-NIL may act by reducing the activity of metalloproteases in
      cartilage and the production of IL-1beta by synovium, both of which are known to
      play a major role in the pathophysiology of OA structural changes.

PMID- 9663487
TI  - Type X collagen, a natural component of mouse articular cartilage: association
      with growth, aging, and osteoarthritis.
AB  - OBJECTIVE: To perform a systematic study on the production and deposition of type
      X collagen in developing, aging, and osteoarthritic (OA) mouse articular
      cartilage. METHODS: Immunohistochemistry was employed to define the distribution
      of type X collagen and Northern analyses to determine the messenger RNA levels as
      an indicator of the synthetic activity of the protein. RESULTS: Type X collagen
      was observed in the epiphyseal and articular cartilage of mouse knee joints
      throughout development and growth. Type X collagen deposition in the transitional
      zone of articular cartilage became evident toward cessation of growth, at the age
      of 2-3 months. The most intense staining for type X collagen was limited to the
      tidemark, the border between uncalcified and calcified cartilage. Northern
      analysis confirmed that the type X collagen gene is also transcribed by articular
      cartilage chondrocytes. Intense immunostaining was observed in the areas of OA
      lesions, specifically, at sites of osteophyte formation and surface fibrillation.
      Type X collagen deposition was also seen in degenerating menisci. CONCLUSION:
      This study demonstrates that type X collagen is a natural component of mouse
      articular cartilage throughout development, growth, and aging. This finding and
      the deposition of type X collagen at sites of OA lesions suggest that type X
      collagen may have a role in providing structural support for articular cartilage.

PMID- 9663488
TI  - Vascular cell adhesion molecule 1 (CD106) on primary human articular
      chondrocytes: functional regulation of expression by cytokines and comparison
      with intercellular adhesion molecule 1 (CD54) and very late activation antigen 2.
AB  - OBJECTIVE: To investigate the expression of adhesion molecules belonging to the
      immunoglobulin superfamily on human primary articular chondrocytes and to
      determine their response pattern to cytokines with respect to the adhesion of
      lymphocytes. METHODS: The expression of adhesion molecules was studied by flow
      cytometry (cultured cells), immunohistochemistry (cartilage), reverse
      transcription-polymerase chain reaction, and Northern blotting. Adhesion of T
      cells to chondrocytes was measured using the Jurkat T cell line. RESULTS:
      Vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1
      (ICAM-1) were found to be constitutively expressed on large percentages of
      unstimulated chondrocytes in culture and in cartilage ex vivo. ICAM-2, ICAM-3,
      and very late activation antigen 4 (VLA-4; alpha4beta1 integrin), the ligand for
      VCAM-1, were not detected. Interleukin-1beta (IL-1beta) and tumor necrosis factor
      alpha (TNFalpha) further induced VCAM-1 and ICAM-1 messenger RNA and protein
      expression. Transforming growth factor beta (TGFbeta) had no effect on ICAM-1 and
      decreased the expression of VCAM-1. Another adhesion molecule, VLA-2 alpha2beta1
      integrin) that was also expressed on unstimulated chondrocytes, was
      differentially regulated by cytokines. While neither IL-1beta nor TNFalpha had
      any effect on expression of VLA-2, TGFbeta markedly increased the alpha2 subunit
      of VLA-2. Adhesion of Jurkat T cells to chondrocytes was further induced by IL
      1beta and TNFalpha. Pretreatment of chondrocytes with monoclonal antibodies to
      VCAM-1 and ICAM-1 inhibited adhesion of T cells to chondrocytes. CONCLUSION: VCAM
      1, ICAM-1, and VLA-2 are constitutively expressed by human articular
      chondrocytes. Expression is regulated by cytokines. As shown for other
      chondrocyte genes, IL-1beta/TNFalpha and TGFbeta antagonistically modulate the
      expression of adhesion molecules. VCAM-1 and ICAM-1 contribute to adhesion of T
      lymphocytes to chondrocytes, and may thus participate in host defense mechanisms
      during inflammatory joint conditions such as rheumatoid arthritis and after
      cartilage transplantation.

PMID- 9663489
TI  - Different distribution of HLA class II and tumor necrosis factor alleles (TNF
      308.2, TNFa2 microsatellite) in anti-topoisomerase I responders among scleroderma
      patients with and without exposure to quartz/metal dust.
AB  - OBJECTIVE: To investigate the influence of quartz/ metal dust exposure on the
      pathogenesis of systemic sclerosis (SSc; scleroderma), by an immunogenetic
      comparison of HLA class II and tumor necrosis factor (TNF) alleles in patients
      with and without exposure. METHODS: A retrospective study of 30 SSc patients
      exposed to quartz/metal dust (qSSc) and 50 patients with idiopathic SSc (iSSc)
      was conducted by DNA-based typing of HLA, TNF-308, and TNFa/b microsatellite
      alleles. RESULTS: A neutral or protective haplotype in iSSc anti-topoisomerase I
      (anti-topo I) responders was found to be a susceptibility haplotype in qSSc
      patients. HLA-DRB1*0301 (DR3), a component of the extended haplotype HLA
      DQA1*0501;B1*0201;DRB1*0301; TNF-308.2;TNFa2/b3, had a decreased frequency in
      iSSc anti-topo I responders compared with non-responders (P = 0.03, odds ratio
      [OR] 0.11, 95% confidence interval [95% CI] 0.00-0.95), but a significantly
      increased frequency in qSSc anti-topo I responders compared with controls and
      with iSSc anti-topo I responders (P = 0.00004, Pcorr = 0.006, OR 11.38, 95% CI
      3.17-44.35 and P = 0.0002, Pcorr = 0.02, OR 30.0, 95% CI 2.05-986, respectively).
      In contrast, DRB1*1104 (DR5) and DRB1*11/15 (DR5/DR2) with no TNF-308.2 and TNFa2
      alleles were prevalent in only the iSSc anti-topo I responders compared with
      controls (P = 0.0005, Pcorr = 0.04, OR 11.0; 95% CI 2.68-45.93 and P = 0.0002,
      Pcorr = 0.02, OR 12.43, 95% CI 3.65-40.04, respectively). CONCLUSION: The
      mechanisms that lead to the development of anti-topo I in qSSc and iSSc patients
      are suggested to be distinct, although it is not clear that the two diseases
      themselves are different.

PMID- 9663490
TI  - Multiple myeloma-associated amyloidosis and giant cell arteritis.
AB  - Primary systemic amyloidosis has been associated with the development of symptoms
      and clinical features characteristic of polymyalgia rheumatica and/or giant cell
      arteritis (GCA). Case reports of this clinical entity have been published,
      stating that the amyloid deposition leads to the symptoms of vasculitis. In this
      report, we present a second case in the English literature of a patient
      presenting with multiple myeloma-associated amyloidosis and GCA. This is the
      first case in which the histopathologic findings are described in enough detail
      to suggest a pathogenic relationship between the two diseases.

PMID- 9663491
TI  - Acalculous ischemic gallbladder necrosis in the catastrophic antiphospholipid
      syndrome.
AB  - A 29-year-old woman was referred for abdominal pain. Results of tests for lupus
      anticoagulant and antibodies to phosphatidylserine and to beta2-glycoprotein I
      were positive, but the patient had no features of systemic lupus erythematosus
      (SLE). Abdominal ultrasonography showed a thickening of the gallbladder wall
      without cholelithiasis. A surgical procedure revealed necrotic areas of the
      gallbladder wall, and a cholecystectomy was performed. Histologic examination of
      the gallbladder showed multiple thrombi and no vasculitis. Despite full-dose
      heparin, the patient developed a catastrophic antiphospholipid syndrome (APS) and
      subsequently died. Among connective tissue disorders, acute acalculous
      cholecystitis has been reported in patients with polyarteritis nodosa and/or SLE.
      APS should be considered as a possible cause of acalculous cholecystitis.

PMID- 9663492
TI  - Paraparesis in a patient with systemic sclerosis.

PMID- 9663493
TI  - Inflammatory myopathy and hepatitis C virus infection.

PMID- 9663494
TI  - Nonsystemic necrotizing vasculitis of the peripheral nervous system.

PMID- 9663495
TI  - Clinical image: Radiographic presentation of hemochromatosis.

PMID- 9663496
TI  - Use of various methods for anticardiolipin detection in the updated American
      College of Rheumatology revised criteria for the classification of systemic lupus
      erythematosus: comment on the letter by Hochberg.

PMID- 9663497
TI  - Experience with methotrexate-associated pneumonitis in northeastern England:
      comment on the article by Kremer et al.

PMID- 9663498
TI  - Prevalence of serum apolipoprotein E4 isoprotein is not increased in rheumatoid
      arthritis patients with amyloidosis: comment on the article by Hasegawa et al.

PMID- 9663499
TI  - Heterotopic ossification in critically ill patients: comment on the article by
      Goodman et al.

PMID- 9663500
TI  - Brain networks affected by synchronized sleep visualized by positron emission
      tomography.
AB  - Nineteen lightly sleep-deprived healthy volunteers were examined with H2(15)O and
      positron emission tomography (PET). Scanning was performed during wakefulness and
      after the subjects had fallen asleep. Sleep stage was graded retrospectively from
      electroencephalogram (EEG) recordings, and scans were divided into two groups:
      wakefulness or synchronized sleep. Global flow was quantified, revealing no
      difference between sleep and wakefulness. A pixel-by-pixel-blocked one-way
      analysis of variance (ANOVA) was performed after correcting for differences in
      anatomy and global flow. The sum of squares of the z-score distribution showed a
      highly significant (P < 0.00001) omnibus difference between sleep and
      wakefulness. The z-score images indicated decreased flow in the thalamus and the
      frontal and parietal association cortices and increased flow in the cerebellum
      during sleep. A principal component (PC) analysis was performed on data after
      correction for global flow and block effects, and a multivariate analysis of
      variance (MANOVA) on all PC scores revealed significant (P = 0.00004) differences
      between sleep and wakefulness. Principal component's 2 and 5 correlated to sleep
      and revealed distinct networks consisting of PC 2, cerebellum and frontal and
      parietal association cortices, and PC 5, thalamus.

PMID- 9663501
TI  - Noninvasive quantification of the cerebral metabolic rate for glucose using
      positron emission tomography, 18F-fluoro-2-deoxyglucose, the Patlak method, and
      an image-derived input function.
AB  - The authors developed and tested a method for the noninvasive quantification of
      the cerebral metabolic rate for glucose (CMRglc) using positron emission
      tomography (PET), 18F-fluoro-2-deoxyglucose, the Patlak method, and an image
      derived input function. Dynamic PET data acquired 12 to 48 seconds after rapid
      tracer injection were summed to identify carotid artery regions of interest
      (ROIs). The input function then was generated from the carotid artery ROIs. To
      correct spillover, the early summed image was superimposed over the last PET
      frame, a tissue ROI was drawn around the carotid arteries, and a tissue time
      activity curve (TAC) was generated. Three venous samples were drawn from the
      tracer injection site at a later time and used for the spillover and partial
      volume correction by non-negative least squares method. Twenty-six patient data
      sets were studied. It was found that the image-derived input function was
      comparable in shape and magnitude to the one obtained by arterial blood sampling.
      Moreover, no significant difference was found between CMRglc estimated by the
      Patlak method using either the arterial blood sampling data or the image-derived
      input function.

PMID- 9663502
TI  - Cocaine decreases cortical cerebral blood flow but does not obscure regional
      activation in functional magnetic resonance imaging in human subjects.
AB  - The authors used functional magnetic resonance imaging (fMRI) to determine
      whether acute intravenous (i.v.) cocaine use would change global cerebral blood
      flow (CBF) or visual stimulation-induced functional activation. They used flow
      sensitive alternating inversion recovery (FAIR) scan sequences to measure CBF and
      blood oxygen level-dependent (BOLD) sensitive T2* scan sequences during visual
      stimulation to measure neuronal activation before and after cocaine and saline
      infusions. Cocaine (0.6 mg/kg i.v. over 30 seconds) increased heart rate and mean
      blood pressure and decreased end tidal carbon dioxide (CO2). All measures
      returned to baseline by 2 hours, the interinfusion interval, and were unchanged
      by saline. Flow-sensitive alternating inversion recovery imaging demonstrated
      that cortical gray matter CBF was unchanged after saline infusion (-2.4 +/- 6.5%)
      but decreased (-14.1 +/- 8.5%) after cocaine infusion (n = 8, P < 0.01). No
      decreases were detected in white matter, nor were changes found comparing BOLD
      signal intensity in cortical gray matter immediately before cocaine infusion with
      that measured 10 minutes after infusion. Visual stimulation resulted in
      comparable BOLD signal increases in visual cortex in all conditions (before and
      after cocaine and saline infusion). Despite a small (14%) but significant
      decrease in global cortical gray matter CBF after acute cocaine infusion,
      specific regional increases in BOLD imaging, mediated by neurons, can be measured
      reliably.

PMID- 9663503
TI  - Temporal patterns of evoked cerebral blood flow during reading.
AB  - This study describes the dynamics of flow activation by reading and investigates
      the potential use of repeated flow velocity measurements for the lateralization
      of speech. Using simultaneous transcranial Doppler recordings from both middle
      cerebral arteries and averaging techniques in 25 healthy volunteers, we describe
      the changes in blood flow velocity caused by repetitive reading tasks of variable
      duration in comparison with a resting state. Reading aloud evoked a
      characteristic temporal flow pattern in both hemispheres, consisting of three
      relative maxima in flow velocity during and after activation. Flow velocities
      lower than baseline were common during longer lasting activation. The amplitudes
      of two of the observed peaks decreased depending on the duration of the task.
      Reading silently produced a markedly different temporal pattern of activation
      than reading aloud. There were individually reproducible significant side to side
      differences. Right-handed persons (n = 15) almost without exception showed a
      significantly higher increase in flow velocity on the left hemisphere (e.g.,
      reading silently 8.7% versus 5.3%; P < 0.0001). Three out of ten left-handed
      individuals, however, exhibited no significant side to side difference or
      exhibited lateralization to the right during one or more of the tasks. These
      findings suggest that reading induces task-specific temporal patterns of regional
      neuronal activity, which show habituation with longer duration of activation.
      Additionally, the observed side to side differences could be useful to predict
      language dominance.

PMID- 9663504
TI  - Activation-induced resetting of cerebral oxygen and glucose uptake in the rat.
AB  - In the clinical setting it has been shown that activation will increase cerebral
      glucose uptake in excess of cerebral oxygen uptake. To study this phenomenon
      further, this study presents an experimental setup that enables precise
      determination of the ratio between cerebral uptake of glucose and oxygen in the
      awake rat. Global CBF was measured by the Kety-Schmidt technique, and the ratio
      between cerebral uptake rates for oxygen, glucose, and lactate was calculated
      from cerebral arterial-venous differences. During baseline conditions, rats were
      kept in a closed box designed to minimize interference. During baseline
      conditions CBF was 1.08 +/- 0.25 mL x g(-1) x minute(-1), and the cerebral oxygen
      to glucose uptake ratio was 5.5. Activation was induced by opening the sheltering
      box for 6 minutes. Activation increased CBF to 1.81 mL x g(-1) x minute(-1).
      During activation cerebral glucose uptake increased disproportionately to
      cerebral oxygen uptake, and the cerebral oxygen to glucose uptake ratio was 4.2.
      The accumulated excess glucose uptake during 6 minutes of activation amounted to
      2.4 micromol/g. Activation was terminated by closure of the sheltering box. In
      the postactivation period, the cerebral oxygen to glucose uptake ratio rose to a
      maximum of 6.4. This response is exactly opposite to the excess cerebral glucose
      uptake observed during activation.

PMID- 9663505
TI  - Characterization of middle cerebral artery occlusion infarct development in the
      rat using fast nuclear magnetic resonance proton spectroscopic imaging and
      diffusion-weighted imaging.
AB  - A nuclear magnetic resonance study of the middle cerebral artery occlusion in the
      rat is presented. Experiments were performed on seven animals before and after
      occlusion, which occurred in situ. The emphasis in this study was on evaluating
      rapid proton spectroscopic imaging. Data were acquired with experimental
      durations of between 4 and 15 minutes for a 32 by 32 spatial matrix, with 64
      spectroscopic data points per spatial element. The spectroscopic data were
      interleaved with diffusion-weighted nuclear magnetic resonance water images of
      the same slice. The study was terminated at about 6 hours after occlusion. The
      brains were then frozen in liquid nitrogen for biochemical imaging. The results
      showed that the signal from N-acetyl aspartate decreased and that of lactate
      increased within the infarcted region. The temporal course of these intensity
      changes varied between animals. Nineteen cortical spreading depressions (CSD)
      were observed by electrophysiologic monitoring during the experiments. Of these,
      11 could be unambiguously detected in the lactate images, and a further 3 were on
      the threshold of detectability. As only a single slice could be examined, it is
      possible that the centers of depression for the remaining 6 CSD were outside the
      slice. To the authors' knowledge, this is the first report of the measurement of
      CSD using proton spectroscopic imaging. Thus, it is shown that this method is
      valuable not only in following the continuous evolution of proton metabolites
      with a good spatial and temporal resolution, but also in observing transient
      phenomena which are believed to play an important role in the expansion of the
      infarcted territory.

PMID- 9663506
TI  - Diffusion-, T2-, and perfusion-weighted nuclear magnetic resonance imaging of
      middle cerebral artery embolic stroke and recombinant tissue plasminogen
      activator intervention in the rat.
AB  - Thrombolysis of embolic stroke in the rat was measured using diffusion (DWI)-, T2
      (T2WI)-, and perfusion (PWI)-weighted magnetic resonance imaging (MRI). An
      embolus was placed at the origin of the middle cerebral artery (MCA) by injection
      of an autologous single blood clot via an intraluminal catheter placed in the
      intracranial segment of internal carotid artery. Rats were treated with a
      recombinant tissue plasminogen activator (rt-PA) 1 hour after embolization (n =
      9) or were not treated (n = 15). Diffusion-weighted imaging, T2WI, and PWI were
      performed before, during, and after embolization from 1 hour to 7 days. After
      embolization in both rt-PA-treated and control animals, the apparent diffusion
      coefficient of water (ADCw) and cerebral blood flow (CBF) in the ischemic region
      significantly declined from the preischemic control values (P < 0.001). However,
      mean CBF and ADCw in the rt-PA-treated group was elevated early after
      administration of rt-PA compared with the untreated control group, and
      significant differences between the two groups were detected in CBF (24 hours
      after embolization, P < 0.05) and ADCw (3, 4, and 24 hours after embolization, P
      < 0.05). T2 values maximized at 24 (control group, P < 0.001) or 48 hours
      (treated group, P < 0.01) after embolization. The increase in T2 in the control
      group was significantly higher at 24 hours and 168 hours than in the rt-PA
      treated group (P < 0.05). Significant correlations (r > or = 0.80, P < 0.05) were
      found between lesion volume measured 1 week after embolization and CBF and ADCw
      obtained 1 hour after injection of rt-PA. Within a coronal section of brain, MRI
      cluster analysis, which combines ADCw and T2 data maps, indicated a significant
      reduction (P < 0.05) in the lesion 24 hours after thrombolysis compared with
      nontreated animals. These data demonstrate that the values for CBF and ADCw
      obtained 1 hour after injection of rt-PA correlate with histologic outcome in the
      tissue, and that the beneficial effect of thrombolysis of an intracranial embolus
      by means of rt-PA is reflected in an increase of CBF and ADCw, a reduction in the
      increase of T2, and a reduction of the ischemic lesion size measured using MRI
      cluster analysis.

PMID- 9663507
TI  - Decreased expression and functionality of NMDA receptor complexes persist in the
      CA1, but not in the dentate gyrus after transient cerebral ischemia.
AB  - The authors investigated the gene expression of the NR2A and NR2B subunits of N
      methyl-D-aspartate (NMDA) receptor and the functional electrophysiologic activity
      of NMDA receptor complexes in the vulnerable CA1 and less vulnerable dentate
      gyrus subfields of the rat hippocampus at different times after transient
      cerebral ischemia. Decreased expression for both subtypes was observed in both
      the CA1 subfield and dentate granule cell layer at early times after challenge;
      however, the decreased expression in the dentate granule cell layer was
      reversible because mRNA levels for both the NR2A and NR2B subtypes recovered to,
      or surpassed, sham-operated mRNA levels by 3 days postchallenge. No recovery of
      expression for either subtype was observed in the CA1 subfield. The functional
      activity of NMDA receptor complexes, as assessed by slow field excitatory
      postsynaptic potentiations (slow f-EPSP) in CA1 pyramidal neurons, was maintained
      at 6 hours postchallenge; however, this activity was diminished greatly by 24
      hours postchallenge, and absent at 7 days postchallenge. A similar pattern was
      observed for the non-NMDA receptor-mediated fast f-EPSP. In dentate granule
      neurons, however, no significant change in NMDA receptor-mediated slow f-EPSP
      from sham control was observed at any time after insult. The non-NMDA receptor
      generated fast f-EPSPs also were maintained at all times postinsult in the
      dentate gyrus. These results illustrate that the activity of NMDA receptors
      remains functional in dentate granule neurons, but not in the pyramidal neurons
      of the CA1 subfield, at early and intermediate times after transient cerebral
      ischemia, and suggest that there is a differential effect of ischemia on the
      glutamatergic transmission systems in these two hippocampal subfields.

PMID- 9663508
TI  - Diffusion of radiotracers in normal and ischemic brain slices.
AB  - Diffusion in the extracellular space (ECS) is important in physiologic and
      pathologic brain processes but remains poorly understood. To learn more about
      factors influencing tissue diffusion and the role of diffusion in solute-tissue
      interactions, particularly during cerebral ischemia, we have studied the kinetics
      of several radiotracers in control and hypoxic 450-microm hippocampal slices and
      in 1,050-microm thick slices that model the ischemic penumbra. Kinetics were
      analyzed by nonlinear least squares methods using models that combine
      extracellular diffusion with tissue compartments in series or in parallel.
      Studies with 14C-polyethylene glycol confirmed prior measurements of
      extracellular volume and that ECS shrinks during ischemia. Separating diffusion
      from transport also revealed large amounts of 45Ca that bind to or enter brain as
      well as demonstrating a small, irreversibly bound compartment during ischemia.
      The rapidity of 3H2O entry into cells made it impossible for us to distinguish
      intracellular from extracellular diffusion. The diffusion-compartment analysis of
      3-O-methylglucose data appears to indicate that 5 mmol/L glucose is inadequate to
      support glycolysis fully in thick slices. Unexpectedly, the diffusion coefficient
      for all four tracers rose in thick slices compared with thin slices, suggesting
      that ECS becomes less tortuous in the penumbra.

PMID- 9663509
TI  - Low extracellular dopamine levels are maintained in the anoxic turtle (Trachemys
      scripta) striatum.
AB  - The uncontrolled increase of extracellular dopamine (DA) has been implicated in
      the pathogenesis of hypoxic/ischemic damage in the mammalian brain. But unlike
      the harmful release of excitatory neurotransmitters such as glutamate and
      aspartate, which occurs on brain depolarization, excessive extracellular DA
      levels occur even with mild hypoxia in the mammalian brain. The purpose of this
      study was to determine whether hypoxia/anoxia provokes a similar increase in the
      anoxic tolerant turtle brain. Extracellular DA was measured in the striatum of
      the turtle using microdialysis followed by high-performance liquid chromatography
      analysis. Results show that extracellular DA was held to normoxic levels over 4
      hours of anoxia. Treatment with the specific DA transport blocker GBR 12909
      during anoxia resulted in a significant increase in DA to 236% over basal levels.
      The ability to maintain low striatal extracellular DA may be an important
      adaptation for anoxic survival in the turtle brain; a contributing factor is the
      continued functioning of DA uptake mechanisms during anoxia.

PMID- 9663510
TI  - Impairment in biochemical level of arterial dilative capability of a cyclic
      nucleotides-dependent pathway by induced vasospasm in the canine basilar artery.
AB  - The authors investigated the changes and the potential of cyclic nucleotide
      dependent signal transduction, which induces smooth muscle relaxation, in the
      basilar artery with severe vasospasm in dogs with double experimental
      subarachnoid hemorrhage (SAH) to explore at which biochemical level the arterial
      dilative capability was impaired. The amount of cyclic adenosine and guanosine
      monophosphates (cAMP and cGMP) decreased significantly in the basilar artery
      after SAH. The activities of adenylate and guanylate cyclases also were decreased
      significantly in the smooth muscle cells of the basilar artery 4 days after SAH.
      In addition to the failure of the pathways to produce cyclic nucleotides, the
      activities of cAMP- and cGMP-dependent protein kinases, which are representative
      actual enzymes that amplify the signal for vascular dilation, also significantly
      decreased together with the almost total loss of activation by cyclic nucleotides
      in the same basilar artery after SAH. It was revealed that the system for smooth
      muscle relaxation was impaired severely in the cerebral arteries with severe
      vasospasm after SAH, on the biochemical basis of significantly less vasodilative
      capability and in several of the steps to produce the cyclic nucleotides of
      intracellular signal transduction.

PMID- 9663511
TI  - Gender differences in clinical manifestations before AIDS diagnosis among
      injecting drug users.
AB  - We compared incidence rates of self-reported HIV-related symptoms and illnesses,
      verified clinical manifestations and findings on physical examination between
      female and male injecting drug users (IDU) stratified by HIV serostatus in the
      Amsterdam cohort study on the natural history of HIV infection. HIV-positive
      female IDU (n = 100) reported a higher frequency of several symptoms and
      illnesses than male IDU (n = 139). Symptoms were reported more chronically by
      women compared to men, while clinical manifestations were reported by a greater
      proportion of women affected by these illnesses compared to men. In HIV-negative
      IDU (163 women and 232 men) the incidence rates were lower compared to HIV
      positives, and a similar gender effect on reported symptoms and illnesses was
      found. Adjusting for biological, behavioral, demographic and study related
      variables did not change the gender effect on clinical manifestations
      substantially. We conclude that the gender effect among HIV-positive IDU was not
      caused by a differential impact of HIV infection on the incidence of the studied
      clinical manifestations among female and male IDU, but reflects a higher
      morbidity of female IDU compared to male IDU.

PMID- 9663512
TI  - Mycobacterium genavense in AIDS patients, report of 24 cases in Italy and review
      of the literature.
AB  - Mycobacterium genavense is a frequently missed agent of disseminated disease in
      AIDS patients. The increasing frequency with which such organism is being
      isolated in Italy suggested a comparison of local survey with data reported in
      literature. Isolates presumed to belong to the species M. genavense were
      centralized and identified by means of genomic sequencing and/or HPLC analysis of
      cell wall mycolic acids; clinical data were obtained from relevant patients'
      record and collected using a proper questionnaire. In 24 cases in which this
      organism has been isolated in Italy M. genavense was grown, prevalently from
      blood, in liquid medium after an average of six weeks of incubation. In
      overwhelming majority, patients were males, presented other opportunistic
      diseases and were characterized by very low CD4+ counts (average 23/microl); most
      frequent symptoms were fever, anemia and weight loss. All but two patients, who
      died before the mycobacterial infection was diagnosed, were treated with at least
      three drugs; the mean survival was close to one year. A review of literature
      reports revealed a wide overlapping of clinical and microbiological features.

PMID- 9663513
TI  - Sexual and non-sexual intrafamilial spread of hepatitis C virus: intrafamilial
      transmission of HCV.
AB  - The rate of intrafamilial transmission of the hepatitis C virus (HCV) was
      investigated in 90 family members of 41 index patients with type C chronic liver
      disease. Antibody to HCV (anti-HCV) was detected by the EIA method (Abbott-Axsym
      Sys) and Hepatitis C virus RNA, by the polymerase chain reaction (Nested PCR). We
      also investigated the presence of anti-HCV in 350 healthy persons (control
      group). The subjects in the study included 38 spouses, 45 children and others (1
      relative and 6 parents). Four family members including 3/38 (7.8%) spouses and 1
      sister were found to be positive for anti HCV antibodies but none had HCV RNA.
      Anti-HCV was not detected in the children of index patients. The prevalence of
      anti-HCV in the families of index patients was significantly higher than in the
      controls (4.3% versus 0.85%) (p = 0.0355). We concluded that the intrafamilial
      transmission of HCV is possible but occurs at a low rate.

PMID- 9663514
TI  - Hepatitis C virus infection in family setting.
AB  - To evaluate risk factors associated with intrafamiliar transmission of hepatitis
      C virus (HCV), 113 hepatitis C virus index subjects with chronic HCV infection
      and their 267 family contacts were studied from January 1994 to October 1995.
      Overall, 16 family contacts (6%) were positive for anti-HCV by ELISA II
      generation. The prevalence was 11.3% in spouses and 2.9% in other relatives (odds
      ratios: 4.2; 95% CI: 1.4-12.6). Spouses who had been married to the index cases
      longer than 20 years had a 7.5-fold risk (95% CI: 1.0-336.3) of HCV
      seropositivity as compared to those married less than 20 years. In univariate
      analysis HCV seropositivity was associated with surgical intervention, use of
      glass syringes and hospitalization. The results of multivariate logistic analysis
      showed that any parenteral exposure (odds ratios: 3.8; 95% CI: 1.2-12.8) and
      sexual contact with an anti-HCV index case (odds ratios: 3.0; 95% CI: 1.0-9.4)
      were both independent predictors of HCV seropositivity among household contacts
      of HCV positive index cases. These findings indicate that sexual contact and any
      parenteral exposure both play an independent role in the spread of HCV infection
      in the family setting.

PMID- 9663515
TI  - A study of familial aggregation of depression, dementia and Parkinson's disease.
AB  - Depression is often accompanied by other disorders including Alzheimer's disease
      and Parkinson's disease. We studied the familial aggregation of these disorders
      in order to examine the possibility of a shared genetic origin. In a population
      based study of 6596 subjects, we studied the association of self-reported
      depression, which required treatment by a psychiatrist, to family history of
      psychiatric disease, dementia, and Parkinson's disease. A family history of
      psychiatric disease was significantly associated with overall depression as well
      as with unipolar (n = 303 patients) and bipolar (n = 27 patients) depression. The
      risk of unipolar depression was associated with the presence of two or more
      demented individuals among their first degree relatives (e.g. parents, siblings
      and children). Since there was no evidence for familial aggregation in subjects
      with only one demented relative, our study suggests that unipolar depression may
      be associated specifically to a strongly familial, form of dementia. The risk of
      bipolar depression was increased for those with one or more relatives with
      dementia and, perhaps, for those with relatives with Parkinson's disease. The
      familial aggregation of depression with dementia and perhaps Parkinson's disease
      suggests that there may be shared susceptibility gene(s) underlying these
      diseases. Our study indicates further that there may be differences in the
      genetic etiology between unipolar and bipolar depression.

PMID- 9663516
TI  - Is the prevalence of atopic diseases in East and West Germany already converging?
AB  - Studies comparing respiratory health of residents in the areas of former East and
      West Germany have shown higher rates of asthma and allergies in children and
      young adults in former West Germany. It has been speculated that some factors
      associated with western lifestyle may be related to higher rates of atopic
      diseases among residents of former West Germany. We examined if the prevalence
      rates of self-reported asthma and nasal allergies in adults converged between the
      areas of former East and West Germany five years after re-unification. During the
      years 1990-1992 and 1994-1995 two independently drawn random samples of more than
      3,000 subjects between the ages of 20 to 44 years answered a screening
      questionnaire of the European Community Respiratory Health Survey in Erfurt (East
      Germany) and in Hamburg (West Germany). The prevalence rates of asthma attacks,
      asthma medication use, allergic rhinitis, and wheezing remained stable in Hamburg
      but increased significantly in Erfurt approaching those of Hamburg. The data
      indicate that there is a tendency for the prevalence rates of self-reported
      allergic rhinitis and asthma-related respiratory symptoms in the eastern part of
      Germany to increase to West-German levels. It is not yet clear if this is due to
      a true increase in morbidity or only to a higher awareness for these diseases
      among doctors and the public.

PMID- 9663517
TI  - Increasing risk of asthma without other atopic diseases in school children: a
      repeated cross-sectional study after 13 years.
AB  - Some children develop asthma and other atopic diseases, others asthma without
      atopic diseases. To better understand secular trends, we estimated the relative
      increase in asthma in children with (atopy related asthma) and without (non-atopy
      related asthma) other atopic diseases (eczema or hay fever) in two samples of
      school children born, 1965-1975 (n = 1674) and 1978-1988 (n = 2188). By analysing
      the samples as historical cohorts, age-specific prevalence rates were estimated
      and incidence rates were calculated (number of new cases by 1000 person years
      under risk). Cox regression was used to estimate the relative risk (RR) of asthma
      by year of birth. The point prevalence of asthma was 1.9% (95% CI: 1.4-2.4) in
      the 1965-1975 cohort and 4.6% (95% CI: 3.8-5.4) in the 1978-1988 cohort for three
      year old children, and remained fairly constant throughout childhood. The age
      specific prevalence of non-atopy related asthma increased relatively more from
      1965-1975 to 1978-1988 compared to atopy related asthma. The age-specific
      incidence rates of asthma showed that the RRs comparing the two cohorts tended at
      all ages to be highest for non-atopy related asthma. The relative risks of non
      atopy related asthma by gender and birth cohort, showed that the effect of cohort
      was higher for non-atopy related asthma, aRR: 4.0 (95 % CI: 2.5-6.5), than for
      atopy-related asthma aRR: 2.0 (95% CI: 1.3-3.2). Children without other atopic
      diseases have a higher relative risk of being diagnosed with asthma than children
      with other atopic diseases across all ages comparing two samples of school
      children born 1965-1975 and 1978-1988.

PMID- 9663518
TI  - The differences in health concerns between mothers and health care professionals
      in a preventive community set up.
AB  - To assess the degree to which mothers, nurses and pediatricians share common
      concerns regarding infants' health and well-being a cross-sectional survey with
      stratified demographic sampling was conducted. A 12-item questionnaire pertaining
      to health concerns was administered to 22 mothers of infants between 1 and 18
      months of age, treated at six Well Baby community clinics with 36 nurses and 25
      pediatricians. Mothers and health care professionals expressed significantly
      different concerns. Pediatricians and nurses shared a more similar order of
      concerns. However, they too differed on the degree of concern related to some of
      the health issues, i.e. nurses perceived the issues related to feeding,
      behaviour, skin, sleep and daily routines as significantly more important than
      did pediatricians. Additional efforts should be devoted to improve and clarify
      communication between mothers and health care professionals.

PMID- 9663519
TI  - Reliability of data on smoking habit and coffee drinking collected by personal
      interview in a hospital-based case-control study.
AB  - A study on the reliability of information on smoking habits and coffee drinking
      collected via interview was conducted among 500 subjects enrolled in a case
      control study on bladder cancer in Brescia, North Italy. A total of 215 cases
      (incident and prevalent) and 285 controls were interviewed personally in the
      hospital setting by a first interviewer, and then re-interviewed by telephone by
      either the same interviewer or another one. Agreement between the first and
      second interview was evaluated using the kappa statistic and the intra-class
      correlation coefficient and via multiple logistic regression modelling. No
      important differences in reliability were found according to sex, education or
      case/control status, while agreement was better among subjects below 65 than
      among older ones, and among incident than prevalent cases. A slightly better
      agreement was found among subjects interviewed twice by the same interviewer than
      those interviewed by two different individuals, which may reflect the presence of
      inter-observer reliability for the latter. Overall, these results show a very
      high reliability of data on smoking and a fairly high reliability regarding
      coffee drinking as collected through face-to-face interviews.

PMID- 9663520
TI  - Moulds and mycotoxins in herb tea and medicinal plants.
AB  - The level of toxigenic moulds and mycotoxins were analyzed in 62 samples of
      medicinal plant material and 11 herbal tea samples. The most predominant fungi
      detected were: Aspergillus, Penicillium, Mucor, Rhizopus, Absidia, Alternaria,
      Cladosporium and Trichoderma. Aspergillus flavus, a known producer of the
      aflatoxin mycotoxin, was present in 11 or 18% of the 62 medicinal plant samples
      and in 1 or 9% of the herbal tea samples. The medicinal plant samples,
      contaminated with A. flavus were also analyzed for the mycotoxins aflatoxin,
      ochratoxin and zearalenone; ochratoxin was found in one of the 7 samples
      analyzed. This study suggests that medicinal plant material and possibly herbal
      teas, if stored improperly allowing for mould growth, should be analyzed for
      mould and mycotoxin prior to use.

PMID- 9663521
TI  - Influenza A and B epidemic criteria based on time-series analysis of health
      services surveillance data.
AB  - Many countries now have epidemiological surveillance systems using health
      services-based indicators that allow detection of influenza epidemics. However,
      there is no accepted criterion for defining an influenza epidemic. An epidemic
      criterion has been developed, based on a time-series analysis of health services
      based indicators collected on a weekly basis by a surveillance network
      implemented in the Paris region since 1984: the Groupe Regional d'Observation de
      la Grippe (GROG). For each new season, an epidemic threshold is independently
      defined for each health services-based indicator as the upper limit of the one
      sided confidence interval of the expected value calculated from the weekly
      differences between the observed number of events and those predicted by a SARIMA
      model fitted on the non-epidemic data of previous seasons. Epidemic criteria for
      influenza A and B are then defined from the combination of both viral indicators
      and epidemic thresholds of individual health services-based indicators. Among
      health indicators, sick-leave data collected from GP's or the Health Insurance
      system, emergency home medical visits, and influenza-like-illness reported by
      GP's are the most sensitive indicators for the early recognition of epidemics.
      The exceeding of the above mentioned thresholds combined with virological data
      allows the specific detection of influenza A or B epidemics. This time-series
      method of analysing surveillance data provides early and reliable recognition of
      these epidemics.

PMID- 9663522
TI  - The Cuban National Cancer Registry: 1986-1990.
AB  - In Cuba, the illness that produces most deaths among 1-64-year-olds is cancer.
      Over 65, it is the second cause of death after heart diseases. A National Cancer
      Registry was created 1964. Its main goals are to register all malignant neoplasms
      diagnosed in the country, to study this disease from the statistical and
      epidemiological point of view and to aid in the health control and planning of
      cancer fighting resources. This paper presents the results based on cases
      registered from 1986 to 1990. More than 50% of incidence and mortality caused by
      cancer is confined to the five major primary sites: lung, prostate, colon, breast
      and cervix. World population standardised rates by 100,000 inhabitants for the
      period 1986-1990 were 218.2 in males and 183.7 in females for incidence and 138.4
      in males and 95.1 in females for mortality. Cancer incidence distribution by
      provinces shows two major regions: western-central, where higher risks of lung,
      breast, prostate and colon cancers are found, and eastern where very high risk of
      cervix cancer is observed. Although an improvement of the information quality
      indexes has been reported by the National Cancer registry in the studied period
      of time, quality of the data remained very poor according to the international
      standards. However, the results obtained by the National Cancer Registry seem to
      be a valuable tool to evaluate the cancer burden and, in particular, to control
      and eventually modify the tasks of the National Cancer Control Program in Cuba.

PMID- 9663523
TI  - Secular trends of weight, height and obesity in cohorts of young Portuguese males
      in the District of Lisbon: 1960-1990.
AB  - OBJECTIVE: To examine the secular trend of weight, height and obesity among young
      Portuguese males at the time of military inspection for national conscription
      purposes in the region of Lisbon, during the last thirty years. DESIGN: Cross
      sectional study, based on the review of military census files. SETTING: Military
      selection centre of Lisbon. SUBJECTS AND METHODS: In Portugal, military service
      is obligatory and medical inspections are carried out every year on males at the
      age of twenty. For study purposes, representative samples were taken from the
      young male population undergoing inspection for the Armed Forces on a five year
      basis, between 1960 and 1990 in the region of Lisbon. Weight and height were
      evaluated by a trained team, using standard measurement instruments and
      procedures. RESULTS: A progressive and significant increase in weight, height and
      BMI of the young male population was found between 1960 and 1990. For certain
      variables the increase was also statistically significant within a five-year
      period, as it was the case for height between 1965-1980 and for weight between
      1985-1990. The increase in BMI experienced some minor fluctuation along the
      reference period, however, it was statistically significant between 1985-1990.
      The increase in weight and in BMI was greater in the highest percentiles and
      particularly noticeable between 1985 and 1990. The percentage of young males with
      BMI over 25 kg/m2 was of 8.1% in 1960 and of 18.0% in 1990, while those having a
      BMI over 27 kg/m2 varied between 3.6% and 6.4% in the same period, respectively.
      The percentage of young adult males with BMI higher than 25 kg/m2 doubled between
      1960 and 1990.

PMID- 9663525
TI  - Why do women live longer than men?

PMID- 9663524
TI  - Clonal identification of Aeromonas hydrophila strains using randomly amplified
      polymorphic DNA analysis.
AB  - The suitability of arbitrary primer polymerase chain reaction (RAPD) as a typing
      technique was evaluated by comparing it with pulsed-field gel electrophoresis
      (PFGE) to characterize Aeromonas hydrophila strains isolated from a cluster of
      hospital-acquired infections. Five isolates from patients and 10 isolates from
      the water supply were compared to 10 epidemiologically unrelated strains isolated
      from patients and rivers. Two methods were used to prepare DNA and two primers
      (AP3 and AP5) were selected. The discriminatory power was better with the
      extractive DNA preparation than the boiling method. The discrimination of closely
      related from less related strains by PCR using AP3 was consistent with that by
      PFGE: water supply of Cholet hospital contaminated with Aeromonas species was not
      the source of the cluster of hospital infections and only two patients were
      infected with clonally-related strains. RAPD using primer AP3 was simpler,
      cheaper, and quicker to perform than pulsed-field gel electrophoresis and is well
      suited for the epidemiological study of A. hydrophila isolates.

PMID- 9663526
TI  - Diagnostic role of videothoracoscopy in mediastinal diseases.
AB  - OBJECTIVE: In order to assess the role of videothoracoscopy in the diagnosis of
      mediastinal diseases, we report a retrospective analysis of 52 cases of
      mediastinal biopsy performed with this technique. METHODS: Between January 1992
      and December 1996 52 patients (39 men and 13 women, mean age 53 +/- 29 years)
      with mediastinal lesions were referred to our department for videothoracoscopic
      biopsy. There were eight lesions in the anterior mediastinum, while the remaining
      44 were in the middle (25 right and 19 left). The adenopathies were solitary or
      located in positions not within reach of the mediastinoscope, or combined with
      pulmonary nodules or diffuse pulmonary diseases. RESULTS: The procedure was
      performed from the right side in 30 cases and from the left side in 22. In nine
      cases the complete excision of the mass was achieved. In the eight patients with
      pulmonary disease a wedge resection was carried out at the same time. Diagnosis
      was achieved in all cases of mediastinal and lung disease (100%). No conversion
      to open thoracotomy and no intraoperative complications occurred. The mean
      hospital stay after surgery was 2.3 +/- 1.3 days in the 49 (94.2%) patients with
      no complications. The postoperative complications consisted of one case of fatal
      pulmonary embolism and two cases of prolonged air leak. conclusion: This analysis
      shows that videothoracoscopy is an effective and reliable method of obtaining a
      diagnosis of solitary unilateral mediastinal lesions or of adenopathies not
      within reach of the mediastinoscope. In some cases it also allows the complete
      excision of the mass. If a procedure on the lung such as a wedge resection is
      needed, it can be performed at the same time. Since this is a strictly unilateral
      procedure, it cannot be used in routine preoperative lung cancer staging.

PMID- 9663527
TI  - Esophageal foreign bodies.
AB  - OBJECTIVE: A retrospective review was performed on 180 patients from 1975 to 1997
      to evaluate the diagnosis, and management of esophageal foreign bodies. METHODS:
      All patients except two were symptomatic and 145 of them were younger than 14
      years of age. Plain films were performed in every patient with a suspected
      esophageal foreign body (EFB). In all patients, rigid esophagoscopy was done
      under general anesthesia once the diagnosis of impacted EFB is made. RESULTS:
      Fifty-five percent of the foreign bodies were coins. In children, the majority of
      impacted esophageal foreign bodies were located at the level of the
      cricopharyngeus muscle while in adults the site of impaction was the lower
      esophageal sphincter. The most common symptoms were vomiting and or
      regurgitation. Of the 180 EFBs encountered, 169 were extracted endoscopically,
      five were pushed into the stomach, five were not found, and one patient needed
      cervicotomy. There were no deaths in this series. Predisposing factors were found
      in 15 patients. Fifteen patients (8.3%) had benign strictures. In ten patients
      (5.5%), minor complications were encountered, none of which were
      esophagoscopically related. Alternative diagnostic and therapeutic modalities are
      discussed. CONCLUSIONS: All patients with a history of suspected foreign body
      ingestion should have direct endoscopic examination. If the EFB is not detected a
      thorough radiographic examination, including CT scan, should be performed to
      detect a possible intra- or extraluminal object. Preservation of the airway is
      regarded to be the most important consideration in esophageal foreign body
      management.

PMID- 9663528
TI  - Surgery for congenital heart disease in Europe 1995.
AB  - OBJECTIVE: An attempt was made to find out how many operations were performed in
      Europe in 1995 for congenital heart disease. METHODS: Representatives from the 20
      most active European countries which could supply reliable information were
      contacted. They were asked to contact all surgeons performing significant numbers
      of operations for congenital heart disease in their country. The numbers of
      operations on children under and over 1 year operated on with and without
      cardiopulmonary bypass were collected. No attempt was made to collect more
      detailed information such as operative mortality as it was felt that many
      surgeons would be reluctant to give their results and the data would be
      incomplete. RESULTS: A total of 27,976 operations were recorded, of which 20,318
      were performed with cardiopulmonary bypass and 7658 without. The total population
      of the 20 European countries was 448 million and the mean number of operations
      performed with cardiopulmonary bypass per million was 45.4. However, the rate
      varied from 9.1 to 70.1. The percentage of operations on cardiopulmonary bypass
      performed in the first year of life varied from 9.4% to 44.4%. CONCLUSIONS: The
      total of nearly 28,000 operations in 1995 is probably an underestimate, but it
      has been difficult to collect this data at all. Obviously many smaller countries
      have not been included, and some older patients undergoing operations such as
      atrial septal defect closure in adult units have been missed. The number of open
      heart operations per million vary in different countries and this presumably
      represents differing referral patterns. If their numbers are low in some
      countries, these results may be helpful in persuading their governments that more
      resources are needed for congenital heart surgery. It is also interesting to see
      the variation in the number of operations performed in the first year of life.
      Those countries with a lower rate may have a backlog of older patients who were
      previously palliated, or their surgeons may still prefer initial palliation and
      later correction in some conditions rather than early correction. It is hoped
      that with better prospective data collection, an assessment can be repeated in
      2000.

PMID- 9663529
TI  - Establishment of total cavopulmonary connection without use of cardiopulmonary
      bypass.
AB  - OBJECTIVE: To minimize deleterious postoperative influences of cardiopulmonary
      bypass on the pulmonary circulation immediately after the Fontan type procedure,
      total cavopulmonary connection was achieved without use of cardiopulmonary
      bypass. METHODS: Since April 1996, 15 patients including five patients with
      visceral heterotaxy, in whom no intracardiac procedure was needed, have undergone
      this operative maneuver. Age at operation ranged from 1.2 to 44.6 years.
      Construction of a systemic to pulmonary shunt had been previously employed in
      seven patients, banding of the pulmonary trunk in two patients, and the Norwood
      procedure in one patient. The superior caval vein was initially anastomosed to
      the pulmonary arteries in bidirectional fashion under temporary bypass from the
      superior caval vein to the atrium. The channel for draining the inferior caval
      vein was subsequently constructed with the aid of temporary bypass from the
      inferior caval vein to the atrium, using a Goretex tube in ten patients, using a
      pedicled autologous pericardial roll in four patients, and directly anastomosing
      the pulmonary trunk to the orifice of the inferior caval vein in one patient. In
      patients with visceral heterotaxy and an independent hepatic venous drainage,
      redirection of the blood flow via the caval vein as well as the hepatic vein
      could be successfully achieved by placing dual temporary bypasses into these
      veins. RESULTS: Postoperative courses were excellent in all patients. Superior
      caval venous pressure was 11 +/- 2 mmHg at 12 h after the operation. No blood
      transfusion was needed in nine patients(60%). CONCLUSION: This alternative
      operative procedure is undoubtedly attractive when establishing the Fontan
      circulation in patients undergoing no intracardiac maneuvers.

PMID- 9663530
TI  - Fontan modification for subsequent non-surgical Fontan completion.
AB  - OBJECTIVE: Establishment of Fontan circulation in complex univentricular hearts
      often requires several surgical procedures. We developed a procedure which
      maintains the advantages of a staged approach, however, during the initial
      surgery additional preparatory measures are performed to allow subsequent non
      surgical Fontan completion. METHODS: The operation is a lateral baffle Fontan
      procedure. The baffle bears multiple perforations to allow the inferior vena cava
      blood to drain into the systemic atrium. Total cavopulmonary connection is
      performed as usual and the cardiac end of the superior vena cava is subtotally
      banded. Formally the operation establishes a bi-directional Glenn physiology.
      During subsequent catheter intervention the banding of the superior vena cava is
      dilated and the holes in the baffle are closed with appropriate devices. RESULTS:
      From April 1994 to December 1995, 18 children having at least two risk factors
      for Fontan operation received the above described operation. Ages ranged from 3
      months to 15 years. Ten patients had one or more previous operations. Bypass time
      ranged from 86 to 128 min and cross clamp time from 14 to 79 min. O2 saturation
      after discontinuation of cardiopulmonary bypass was 76% (70-81%). The
      postoperative recovery of all patients was rapid with early extubation (mean 6 h)
      and discharge to the ward the morning of the first postoperative day. One patient
      died. No fluid retention as pericardial, pleural or abdominal fluid effusions
      occurred. At discharge O2 saturation was 77% (75-82%). In thirteen children
      successful conversion to total cavopulmonary connection with interventional
      debanding of the superior vena cava and closure of the fenestrations was
      performed. After a hospital stay of only a couple of days the children were
      discharged with normal O2 saturation after Fontan completion. CONCLUSIONS: We
      suggest that this modification of the staged Fontan procedure reduces the need
      for surgical interventions by applying balloon angioplasty and occluder
      technology to this unique subset of patients.

PMID- 9663531
TI  - Bi-directional cavopulmonary shunt associated with ventriculo and valvuloplasty
      in Ebstein's anomaly: benefits in high risk patients.
AB  - OBJECTIVE: The prognosis for surgical repair of Ebstein's anomaly depends on the
      tricuspid valve repair and on the right ventricular function. In order to
      decrease the preload of the compromised right ventricle, a bi-directional
      cavopulmonary shunt was added to the intracardiac repair. METHODS: Among 113
      patients operated on for Ebstein' s anomaly at our institution from 1980-1997, a
      cohort of 60 patients was selected for high risk for postoperative complications.
      Patients presented with one or more several criteria: massive tricuspid valve
      dysfunction, extended atrialized right ventricle, poor right ventricular
      contractility, or long standing atrial fibrillation. After prior informed
      consent, this cohort was divided into two groups. Both groups had similar
      preoperative clinical patterns: Group I (45 patients), surgical technique
      included longitudinal right ventricular plication and tricuspid valve
      valvuloplasty; Group II (15 patients), where the surgical technique was similar
      to Group I except a bi-directional cavopulmonary shunt was added at the end of
      the procedure. RESULTS: Operative mortality was 24% (11/45) in Group I and 0%
      (0/15) in Group II (P < 0.05). The survival at 5 years was 66.1 +/- 14% in Group
      I and 80 +/- 16% in Group II (not significant). Reoperation rate was 11% (5/45)
      in Group I and 0% (0/15) in Group II. No deleterious effects of the bi
      directional cavopulmonary shunts were observed clinically. Residual tricuspid
      valve insufficiency rate was 26% in both groups. However, patients with the bi
      directional cavopulmonary shunt had a better tolerance and have not needed
      reoperations to date. CONCLUSIONS: In high risk patients with Ebstein's anomaly,
      an associated bi-directional cavopulmonary shunt seems to offer several distinct
      advantages including decreased operative mortality and better tolerance of the
      residual tricuspid valve dysfunction.

PMID- 9663532
TI  - When is extracorporeal life support worthwhile following repair of congenital
      heart disease in children?
AB  - BACKGROUND: Although the use of extracorporeal life support (ECLS) following
      repair of congenital heart defects in children is increasing, the criteria for
      ECLS usage in these patients is not well defined. The overall survival of such
      patients is disappointingly low and may depend on both the indication for support
      and the time at which ECLS is commenced. METHODS: Between January 1993 and
      December 1996, 727 children underwent surgery for congenital heart defects at our
      institution with an overall hospital mortality of 5.8% (42 children). Nine of
      these children were treated with ECLS postoperatively. There were seven males and
      two females with a mean age of 7.2 months (range 2 weeks-3 years). Seven children
      could not be weaned from cardiopulmonary bypass (CPB) in the operating theatre. A
      further two were treated with ECLS later on during the postoperative period
      (commenced at 14 and 48 h). Full veno-arterial extra corporeal membrane
      oxygenation (ECMO) support was used in all children except one in whom a left
      ventricular assist device (LVAD) was used. RESULTS: The median duration of
      support was 121 h (range 15-648 h). Four children (44%) were weaned from support
      and two of these are long-term survivors. Of the seven children in whom ECLS was
      instituted because of failure to wean from CPB, there was one long term survivor
      (LVAD support). Of the two patients in whom ECLS was instituted during the post
      operative period there is one long-term survivor. CONCLUSIONS: Weaning form ECLS
      and decannulation in 44% of our patients is comparable to other series of post
      cardiotomy patients requiring ECLS. However, full veno-arterial ECMO instituted
      because of a failure to wean from CPB during corrective surgery is associated
      with an extremely poor outcome (zero long-term survivors in six patients).

PMID- 9663533
TI  - Superiority of centrifugal pump over roller pump in paediatric cardiac surgery:
      prospective randomised trial.
AB  - OBJECTIVE: The merits of centrifugal pump in adult cardiopulmonary bypass are
      well established. This study compares the effects of the Medtronic Biomedicus
      centrifugal pump with conventionally used roller pump in routine cardiopulmonary
      bypass in infants and children. METHODS: Between June 1996 and March 1997, 42
      children (aged 2 days-13 years) undergoing elective cardiac surgery were assigned
      to either centrifugal or roller pump bypass. The following variables were
      studied: haemolysis (haematocrit, free plasma haemoglobin, haptoglobins),
      platelet activity (platelet counts, Beta-thromboglobulin), leukocyte count,
      cytokine release (IL-2, IL-6, IL-8), complement activation (C3a and C5a), blood
      and blood product requirements, urine output on bypass, post-operative blood
      urea, duration of ventilation, intensive care and hospital stay. RESULTS: Age,
      weight, disease complexity, duration of bypass, and a number of other variables
      were comparable in the two groups. The centrifugal pump resulted in lower plasma
      free haemoglobin (mean +/- SD, 50 +/- 23 vs. 72 +/- 35 mg/dl, P < 0.01), higher
      platelet count (133.1 +/- 34.8 vs. 63.5 +/- 29.6 x 10(9)/l, P < 0.01), less
      platelet activation (beta-TG 1253 +/- 633 vs. 1657 +/- 677 ng/ml; P < 0.05), less
      cytokine release (IL-6 329 +/- 57 vs. 392 +/- 59 pg/ml; P < 0.05), and reduced
      levels of C3a (4822 +/- 274 vs. 5933 +/- 393 ng/ml, P < 0.01). Differences were
      detected in favour of the centrifugal pump in urine output on bypass (4.1 +/- 0.5
      vs. 2.3 +/- 1.9 ml/kg per h, P < 0.01), post-operative maximal urea (6.5 +/- 3.1
      vs. 10.2 +/- 6.7 mmol/l, P < 0.02), ventilation time (18.9 + 6.5 vs. 56.5 + 51.7
      h, P < 0.01), duration of intensive care (1.4 +/- 0.79 vs. 3.33 +/- 2.8 days, P <
      0.05) and hospital stay (5.7 +/- 1.4 vs. 15.75 +/- 23.9 days, P < 0.01), but not
      in blood and blood product requirements (RCC: 11.26 +/- 4.6 vs. 10.77 +/- 4.2
      ml/kg per 24 h, P > 0.05). CONCLUSION: The centrifugal pump as compared to roller
      pump results in less blood trauma, reduced platelet activation and less
      pronounced inflammatory response. There is also an improved renal response during
      and after bypass. This is translated clinically into reduced requirement for
      ventilation, shorter intensive care and hospital stays. These results strongly
      favour the use of centrifugal pump in routine paediatric cardiac surgery.

PMID- 9663534
TI  - Central venous pressure, pulmonary capillary wedge pressure and intrathoracic
      blood volumes as preload indicators in cardiac surgery patients.
AB  - OBJECTIVE: Monitoring of cardiac preload is mainly performed by measurement of
      central venous and pulmonary capillary wedge pressure in combination with
      assessment of cardiac output, applying the pulmonary arterial thermal dilution
      technique. However, the filling pressures are negatively influenced by mechanical
      ventilation and the pulmonary artery catheter is criticized because of its
      inherent risks. Measurement of right atria, right ventricular, global end
      diastolic and intrathoracic blood volume index by arterial thermal dye dilution
      utilizing the COLD-system may represent an alternative. METHODS: In 30 CABG
      patients with an uncomplicated postoperative course the mentioned parameters were
      measured 1, 3, 6, 12 and 24 h postoperatively to prove their qualification as
      preload indicators: As patients received no inotropic support, changes of cardiac
      index and stroke volume index must correlate to changes of presumably preload
      indicating parameters. RESULTS: When arterial and pulmonary arterial thermal
      dilution were compared, no differences were found; the correlation coefficient
      being 0.96, the bias 0.16 l/min per m2 (2.4%) and coefficients of variation did
      not exceed 7%. Changes of central venous pressure, capillary wedge pressure,
      right atrial end diastolic volume index and right ventricular end diastolic
      volume index did not correlate at all to changes of cardiac and stroke volume
      index (coefficients ranged from -0.01 to 0.28). In contrast, intrathoracic and
      global end diastolic blood volume indices with coefficients from 0.76 to 0.87,
      did show a good correlation to cardiac and stroke volume index. CONCLUSION:
      Central venous pressure, capillary wedge pressure, right atrial and right
      ventricular end diastolic volumes are no suitable preload parameters in cardiac
      surgery intensive care, compared to intrathoracic and global end diastolic blood
      volumes. The latter show a higher clinical value and can be obtained by less
      invasive methods, as no pulmonary artery catheter is required.

PMID- 9663535
TI  - Increased preoperative C-reactive protein (CRP)-values without signs of an
      infection and complicated course after cardiopulmonary bypass (CPB)-operations.
AB  - OBJECTIVE: C-Reactive protein (CRP) is known to be a sensitive indicator of
      infection. Since it is also involved in the acute phase reaction, it is of great
      interest, whether an isolated preoperative increase of CRP without further signs
      of infection is of any prognostic value for postoperative outcome after cardiac
      surgery with cardiopulmonary bypass (CPB), which itself is possibly causing a
      systemic inflammatory response syndrome (SIRS). METHODS: Fifty patients with an
      isolated CRP-elevation (>5 mg/l) (from 6.2 to 93.3 mg/l) were operated using CPB
      (group A). A control group (group B) consisted of 50 cardiac surgery patients,
      matched in the patterns of age, gender and kind of disease. No preoperative CRP
      elevation (from 0 to 4.8 mg/l) occurred in this group. RESULTS: The postoperative
      course of both groups showed significant differences. Septic complications were
      seen more often in group A (20%) than in the controls (2%) (P < 0.01).
      Microbiology (blood culture, cultures from nose, tracheal aspirate and urine) was
      positive only in 10% of these patients. Catecholamine support (epinephrine,
      norepinephrine and/or doses of dopamine or dobutamine of more than 3 microg/kg
      per min) was needed in 26% of group A cases, whereas it was only needed in 10% of
      group B (P < 0.05). A significantly longer respiratory support was also necessary
      in patients with elevated CRP (25.2 +/- 6.4 h vs. 6.6 +/- 0.8 h) (P < 0.01).
      Furthermore there was a significant difference in the duration of intensive care
      (4.6 +/- 0.8 days vs. 2.6 +/- 0.3 days) (P < 0.05). CONCLUSIONS: These data show
      that patients without apparent infection or inflammation, who had elevated CRP
      values preoperatively, face an increased risk of septic complications after
      extracorporeal circulation. As microbiology tests are negative in most cases, it
      may be speculated that the majority of septic complications are due to a SIRS.

PMID- 9663536
TI  - Effects of angiotensin converting enzyme inhibition on systemic vascular
      resistance and vasoconstrictor requirements during hypothermic cardiopulmonary
      bypass.
AB  - OBJECTIVE: We proposed that angiotensin converting enzyme (ACE) inhibitor therapy
      would alter systemic vascular resistance (SVR) during rewarming and increase the
      requirement for vasoactive drugs in the immediate post-bypass period. METHODS:
      Sixty-five sequential adult patients undergoing cardiac surgical procedures
      requiring hypothermic (28 degrees C) cardiopulmonary bypass (CPB) were recruited.
      Sixty-two fitted the inclusion criteria of which 21 were receiving ACE inhibitors
      prior to surgery. SVR was calculated at 1 min intervals during the rewarming
      phase of hypothermic CPB. The use of vasoactive drugs during and immediately
      after termination of CPB was recorded. The doctor administering these drugs was
      unaware of the nature of the study. RESULTS: Mean SVR in the ACE group was 978
      dyne/s per cm5 and in the control group was 1194 dyne/s per cm5 (P = 0.006). Mean
      arterial pressure was 48.8 mmHg in the ACE group and 56.3 mmHg in the control
      group (P = 0.004). There was a significant difference in vasoactive drug
      requirements between the groups (P < 0.01). There was no statistically
      significant difference in age, weight, body mass index, body surface area,
      theatre temperature, core temperature at which rewarming started, rate and time
      of rewarming, haematocrit on bypass or preoperative left ventricular function.
      CONCLUSION: Preoperative ACE inhibitor therapy decreases SVR during the rewarming
      phase of CPB and increases post-bypass vasoactive drug requirements.

PMID- 9663537
TI  - Cardiac surgery by transxiphoid approach without sternotomy.
AB  - OBJECTIVE: In a attempt to avoid the potential drawbacks associated with
      sternotomy coupled with a desire for a smaller scar led us to investigate the
      transxiphoid approach without sternotomy. We present our preliminary experience
      and a comparison between the sternal and thoracic approaches. METHODS: From June
      1996, at the Institut Cardiovasculaire Paris Sud, Massy, France (ICPS) and the
      Heart Institute, Sao Paulo, Brazil (HI) the transxiphoid approach was adopted for
      the correction of selected congenital cardiac defects. The xiphoid was resected
      through a 6 cm long vertical skin incision. With a special retractor the sternum
      was elevated cephalad and anteriorly. Closure of the defect was performed in the
      conventional manner. Twenty-six patients; 17 boys and 9 girls were entered into
      the study from representing 19 atrial septal defects (ASDs), 4 ventricular septal
      defects (VSDs) and 3 partial atrio ventricular septal defect (AVSDs). In addition
      at ICPS the transxiphoid approach for correction of ASD was compared to the
      thoracic and sternal approaches performed in the same period. RESULTS: Both the
      aortic cross clamp time as well as the duration of extracorporeal circulation
      were increased when compared to either standard sternotomy or thoracotomy
      approaches. There were no differences within the groups when comparing body
      surface area, amount of chest drainage or length of either ICU or hospital stay.
      However the patients in the transxiphoid group showed less pain and respiratory
      discomfort. CONCLUSION: Our initial experience with the transxiphoid approach
      without sternotomy confirms that it is a promising technique that can be
      considered an alternative to conventional sternotomy. The access is adequate for
      surgical procedures performed through a right atriotomy. The advantages include a
      better cosmetic scar, less surgical trauma, minimal respiratory discomfort and a
      potentially lower risk of infection. However cardiopulmonary bypass and cross
      clamp times are increased. There were no complications, and patient satisfaction
      was high.

PMID- 9663538
TI  - CABG shortly after AMI treated with thrombolysis: an analysis of the surgical
      group and a comparison with PTCA in the DANAMI study. Danish multicenter
      randomized study of invasive versus conservative treatment in patients with
      inducible ischemia after thrombolysis in acute myocardial infarction.
AB  - OBJECTIVE: To present surgical results of the DANAMI study comparing conservative
      and invasive treatment of postinfarction myocardial ischaemia and to compare
      these with percutaneous transluminal angioplasty (PTCA) which was the alternative
      invasive treatment in that study. METHODS: A group of 413 patients with verified
      acute myocardial infarction treated with thrombolysis within 12 h of the onset of
      symptoms, who demonstrated postinfarction myocardial ischaemia were treated with
      coronary artery bypass grafting (CABG) or PTCA. Patients with left main lesions,
      three-vessel disease, two-vessel disease with more than three stenoses and
      patients with occlusions of a non-infarct related vessel had primary CABG.
      Patients with 1- and 2-vessel disease with not more than a total of three
      stenoses had PTCA. In case of failed PTCA patients had secondary CABG. The median
      distance from AMI to CABG was 45 days. PTCA was performed at a mean of 39 days
      after the infarction. RESULTS: A total of 147 patients had CABG and 266 had PTCA.
      The operative mortality for CABG was 1.4%. No PTCA patients died in relation to
      the procedure, 0.8% developed acute myocardial infarction as a consequence of the
      procedure, 1.5% had acute CABG and 3.5% elective CABG due to failed PTCA. In
      spite of more severe coronary artery disease among the CABG patients there was no
      difference in survival at 2.4 years. The CABG group had significantly fewer
      episodes of unstable angina, 10.2% versus 25.6% (P = 0.0002). No CABG patients
      had re-do revascularisation at 2.4 years follow-up versus 15.4% of the PTCA
      patients. At 3 years 80% of the CABG patients were free of angina compared to the
      61% of the PTCA group (P < 0.0001). CONCLUSION: Low morbidity and mortality
      justifies the deferred elective revascularisation in patients with postinfarction
      myocardial ischaemia even in patients with silent ischaemia. There is no
      difference in survival at 2.4 years between CABG and PTCA but CABG offers more
      lasting results concerning incidence of stable and unstable angina than PTCA,
      which, however, is a valuable alternative in patients with less severe coronary
      artery disease.

PMID- 9663539
TI  - Warm blood hyperkalaemic reperfusion ('hot shot') prevents myocardial substrate
      derangement in patients undergoing coronary artery bypass surgery.
AB  - OBJECTIVE: A significant metabolic derangement occurs in the ischaemic-reperfused
      heart of patients undergoing coronary artery bypass surgery using cold blood
      cardioplegia. The aim of the present study was to investigate whether this effect
      could be reversed by complementing cold blood cardioplegia with a short terminal
      exposure of warm blood hyperkalaemic cardioplegia ('hot shot'). METHODS: Thirty
      five patients undergoing primary elective coronary revascularisation were
      randomized to one of two different techniques of myocardial protection. In the
      cold blood group (n = 17) myocardial protection was induced using antegrade
      hyperkalaemic cold blood cardioplegic solution. In the hot shot group (n = 18)
      this was supplemented with a short exposure to hyperkalaemic warm blood
      cardioplegia prior to removal of the cross clamp. Intracellular substrates (ATP
      and amino acids) were measured in left ventricular biopsies collected 5 min after
      institution of cardiopulmonary bypass, after 30 min of ischaemic arrest and 20
      min after reperfusion. RESULTS: Biopsies taken at the end of the period of
      myocardial ischaemia, when compared to control, did not show any significant
      change in the intracellular concentration of ATP (from 2.71 +/- 0.32 to 2.43 +/-
      0.37 micromol g wet for cold blood group and from 2.6 +/- 0.3 to 2.5 +/- 0.34
      micromol/g wet weight for hot shot group) or total free intracellular amino acids
      pool (from 33.0 +/- 1.4 to 30.0 +/- 1.4 micromol/g wet weight for cold blood
      group and from 34.0 +/- 1.4 to 34.5 +/- 2.3 micromol/g wet weight for hot shot
      group). Upon reperfusion, however, there was a significant fall in ATP (23.7 +/-
      1.6 micromol/g wet weight amino acids, P < 0.05) and in amino acids (1.53 +/-
      0.24 micromol/g wet weight, P < 0.05) in the group receiving only cold blood
      cardioplegia but not in the hot shot group (2.27 +/- 0.27 micromol/g wet weight
      ATP and 30.5 +/- 1.6 micromol/g wet weight amino acids). CONCLUSIONS: The data
      suggest that warm blood hyperkalaemic reperfusion hot shot prevents myocardial
      metabolic derangement seen during coronary artery surgery.

PMID- 9663540
TI  - Aortic valve replacement in children: are we on the right track?
AB  - OBJECTIVE: The choice of the ideal prosthesis for aortic valve replacement (AVR)
      in children is still controversial. Early degeneration of bioprostheses and the
      potential risks related to anticoagulation in the child have renewed the interest
      of many surgeons towards the Ross operation. This study concerns our 22-year
      experience with AVR in children. METHODS: Forty-six children, aged 4 months to 16
      years (mean 11.6 years), had AVR between April 1974 and December 1996.
      Preoperative diagnosis revealed aortic regurgitation (AR) in 25 cases, aortic
      stenosis (AS) in ten, combined AS and AR in nine and LVOTO in two patients. Of
      the 46 patients, 26 had 37 previous procedures. Isolated AVR was performed in 19
      cases, 27 children underwent 36 concomitant intracardiac procedures. Mechanical
      prostheses were implanted in 30 children, bioprostheses in eight, aortic
      homografts in three. Five patients underwent a Ross procedure. RESULTS: There was
      one hospital death in the latter group (2.1%). Six of seven late deaths occurred
      in patients who underwent complex intracardiac procedures (15.2%). Reoperation
      rate was 19.5% (n = 10), differentiating 16.6% for mechanical (5/30 patients) and
      50% (4/8 patients) for bioprostheses. The mean follow-up period was 8.01 years,
      ranging from 0.45 to 21.66 years (304.04 patient-years). There was one
      hemorrhagic event (2.1%) due to anticoagulation, thrombosis of the mechanical
      valve occurred in two patients (4.2%). CONCLUSIONS: AVR can be performed with
      acceptable mortality rate and good long-term results in children. We perform the
      Ross operation only in selected cases. According to our experience, mechanical
      prostheses show excellent performances in children with a low incidence of
      complications related to anticoagulation.

PMID- 9663541
TI  - Haemodynamics and left ventricular mass regression: a comparison of the
      stentless, stented and mechanical aortic valve replacement.
AB  - OBJECTIVE: Our objective was to compare the degree of change in hemodynamics and
      left ventricular mass (LVM) regression after aortic valve replacement (AVR) with
      stentless, stented and mechanical valves. METHODS: Patients greater than 59 years
      of age had AVR for aortic stenosis with the stentless xenograft (Cryolife
      O'Brien, CLOB), stented xenograft (Carpentier-Edwards, C-E) or mechanical valve
      (ATS). One-hundred and forty-two patients received stentless, 40 stented, and 69
      mechanical valves (mean age 74 +/- 6 vs. 72 +/- 7 and 67 +/- 6 years,
      respectively). Serial echocardiography was performed. RESULTS: The left
      ventricular outflow tract diameter was similar pre-operatively in the stentless
      versus the stented versus the mechanical groups (2.2 +/- 0.4 vs. 2.3 +/- 0.2 vs.
      2.2 +/- 0.3 cm; P, n.s). The effective orifice area was larger immediately post
      operatively in the stentless versus the stented or the mechanical group (2.4 +/-
      0.4 vs. 2.0 +/- 0.6 vs. 2.0 +/- 0.7 cm2, P = 0.0001 for both comparisons). The
      peak aortic gradient at 6 months was significantly less in the stentless versus
      the stented and mechanical groups (15 +/- 7 vs. 25 +/- 9 vs. 22 +/- 9 mmHg, P <
      0.0001). LVM regressed over 6 months in all subgroups: stentless 272 +/- 64 g vs.
      220 +/- 72 g, P = 0.0001, stented 257 +/- 58 vs. 230 +/- 74 g, P = 0.02, and
      mechanical 267 +/- 95 vs. 204 +/- 54 g, P = 0.003. The reduction in LVM was
      greater in the stentless versus the stented (P = 0.05) but similar to the
      mechanical group. CONCLUSIONS: AVR with the stentless xenograft results in
      superior hemodynamics compared to the stented and mechanical valve replacements.
      AVR in all three groups leads to a significant regression of left ventricular
      hypertrophy within 6 months. However the reduction in LVM is greater in subjects
      with stentless and mechanical valves, which may have prognostic significance.

PMID- 9663542
TI  - Risk of late reoperations in patients with acute type A aortic dissection: impact
      of a more radical surgical approach.
AB  - OBJECTIVE: To evaluate the incidence and risk factors for reoperations on the pre
      isthmic aorta after repair of type A acute aortic dissection. METHODS: From
      January 1979 to December 1996, 178 patients (125 males and 53 females with a mean
      age of 57 +/- 9 years) underwent emergency surgery for acute type A aortic
      dissection with an overall operative mortality rate of 21%. One hundred and forty
      one patients (100 males and 41 females, aged 58 +/- 12 years), were discharged
      after successful replacement of the ascending aorta in 136 cases (96%) with
      extension to the transverse arch in 22 (16.2%) and associated total root or
      aortic valve replacement in 31 (22.8%) and 6 (4.4%) cases, respectively. Intimal
      tear resection and direct primary anastomosis of the aorta were performed in 5
      patients (4%). Total follow-up was 690 patient-years, mean 5.1 +/- 4.1 years,
      with an actuarial survival rate at 5,10 and 15 years of 88%, 73% and 42%,
      respectively. RESULTS: Nineteen patients (13%), 13 males and 6 females, aged 50
      +/- 10 years, required a total of 22 reoperations with an actuarial freedom from
      reoperation at 5, 10 and 15 years of 94%, 64% and 35%, respectively. Initial
      repair consisted of replacement of the ascending aorta in 16 (84%) cases, with
      total root replacement in 2 (12%) and isolated aortic valve replacement in 1
      (6%). Three patients (16%) were treated by intimal tear resection and direct
      primary anastomosis of the aorta. Mean interval between initial repair and
      reoperation was 5.2 +/- 3.1 years and indication to re-do surgery were severe
      aortic regurgitation in 2 (11%), aneurysmal evolution of the false lumen in 4
      (21%) or both in 13 (68%). Extensive aortic reconstruction comprising
      simultaneous graft replacement of the aortic root, ascending aorta and aortic
      arch was necessary in 13 cases (68%), isolated replacement of the ascending aorta
      in 3 (16%), aortic valve in 2 (11%) and aortic arch in 1 (5%). There were 1
      hospital (5%) and 2 late (11%) deaths at a mean follow-up of 2.5 +/- 2.4 years,
      with an actuarial survival at 5 years of 88%. Retrospective analysis of our total
      experience revealed that the introduction of the open distal anastomosis
      technique since 1990, reduced the incidence of reoperation from 11/46 (24%) to
      8/95 (8.4%) (P < 0.05). However, also with this strategy 8/73 (11%) patients
      surviving replacement limited to the ascending aorta required reoperation versus
      none of the 22 patients surviving repair extended to the aortic arch. Three out
      of 5 (60%) patients undergoing intimal tear resection and primary anastomosis of
      the aorta early in our experience, required reoperation. CONCLUSIONS: Management
      of patients with acute type A aortic dissection may include one or more surgical
      procedures after the initial emergency repair. Reoperations carry a low operative
      risk with good long-term survival and their incidence is reduced by routine open
      distal anastomosis and aggressive replacement of the aortic arch. Intimal tear
      resection and primary anastomosis of the aorta appear to be associated with
      increased risk of reoperation.

PMID- 9663543
TI  - Evolution of post-traumatic aortic aneurysm in the subacute phase: magnetic
      resonance imaging follow-up as a support of the surgical timing.
AB  - OBJECTIVES: A recent surgical series documented that in traumatic aortic rupture
      (TAR) a surgical repair postponed to the treatment of associated lesions reduced
      operative and overall mortality. Nevertheless some isolated cases may develop to
      free rupture. Until now, no imaging follow-up studies of post-traumatic aortic
      lesions have been reported in the early stage. The aim of this study is to
      analyze the behaviour of traumatic aortic ruptures in the subacute phase, in
      order to detect the morphological characteristics of unstable post-traumatic
      aneurysms. METHODS: Twenty-five consecutive patients affected by traumatic aortic
      rupture (one intimal hemorrhage, 19 partial lesions and five circumferential
      lesions) were admitted to the department of cardiac surgery. Magnetic resonance
      imaging (MRI) was the imaging method used to confirm the diagnosis. No one was
      operated on during the acute phase. All patients were treated with beta-blockers
      and vasodilators as well as limited fluid administration. Delayed surgery was
      carried out in 18 patients at 243 days (+/-127), after the resolution of
      associated lesions. A scheduled MRI follow-up was performed at 7, 15 and 30 days
      and immediately before the operation. The parameters examined were increase of
      post-traumatic aneurysm, increase of periaortic hematoma and modification of the
      thoracic associated lesions. RESULTS: At 30 days a 3.0 +/- 3.7 mm median increase
      of the aneurysm was observed, while in the subsequent period the lesions became
      substantially stable, resulting in a 4.4 +/- 3.6 mm increment at the end of the
      follow-up. The circumferential lesions presented a higher increment with respect
      to the partial lesions. In three cases an augmentation of 6, 7 and 12 mm was
      detected and surgical repair was anticipated. In 13 cases a periadventitial
      hematoma surrounding the aortic aneurysm decreased through the time. One case of
      intimal hemorrhage healed spontaneously, with no aneurysm formation. Thoracic
      associated lesions (pleural and pericardial effusions, rib fractures, lung focal
      contusions and two cases of ARDS) resolved at 30-60 days. CONCLUSIONS: Despite
      common knowledge, considering TAR highly evolutive in the acute and subacute
      phase, this study demonstrated that this pathological entity is relatively stable
      if a proper pharmacological treatment is administrated. MRI follow-up is
      recommended in order to detect isolated cases of unstable aneurysm.

PMID- 9663544
TI  - Muscle transformation in cardiomyoplasty: the effect of conditioning and
      mobilisation on perfusion, oxygenation and fatigue resistance in the latissimus
      dorsi muscle.
AB  - BACKGROUND: In the clinical application of transformed skeletal muscle to cardiac
      assistance there is evidence that the latissimus dorsi muscle (LDM) wrap can
      undergo atrophy, which would prevent it from providing a sustained functional
      improvement. Possible causes are ischaemia and degeneration related to the
      conditioning process. We studied the nutritional and structural changes occurring
      under different stimulation regimes with the aim of improving the conditioning
      protocol. METHODS: Microelectrodes were used to measure regional perfusion and
      oxygenation in the rabbit LDM during mobilisation and subsequent repeated
      contraction. Group A muscles (n = 10) were conditioned for 6 weeks at 10 Hz,
      Group B muscles (n = 10) for 2 weeks at 2.5 Hz. Each muscle was then mobilised
      and tested in a hydraulic apparatus which recorded the pressure generated in a
      closed circuit. RESULTS: Muscles of Group A and Group B demonstrated
      transformation of fibre type, with a predominance of type I (62 +/- 4%) fibres in
      Group A and type IIa (68 +/- 9%) fibres in Group B. There was no evidence of
      muscle degeneration. After 10 min of fatigue testing the pressure produced was 53
      +/- 5% of initial values in Group A and 51 +/- 8% in Group B, compared to 8 +/-
      1% in the control group (P < 0.001). Maximum rate of relaxation was faster in
      Group B than in Group A (46 +/- 3% vs. 36 +/- 3% of control muscle, P < 0.05).
      Mobilisation resulted in a decrease in the distal perfusion of the control
      muscles (P < 0.05) and PO2 decreased by 8.7 +/- 1.7 mmHg during a fatigue test,
      which resulted in rapid loss of contractile function to 46 +/- 1% of the initial
      value within 1 min. In both Groups A and B the perfusion of all regions of the
      muscles both before and after mobilisation was greater than that of controls.
      During the same fatigue test, the PO2 of the distal regions was maintained and
      the contractile function fell more slowly to between 70 and 80% of initial values
      within 1 min. CONCLUSION: We showed that ischaemia in the distal region of the
      control LDM could result from mobilisation and repeated contraction. Muscle
      transformation improved perfusion and prevented a fall in tissue PO2 during a
      sustained series of contractions. Muscles that were conditioned at 2.5 Hz shared
      the improved perfusion of the fully transformed muscle, but had faster relaxation
      characteristics. Short periods of in situ conditioning prior to mobilisation may
      help to avoid ischaemic changes in distal parts of the LDM while achieving
      fatigue resistance in the grafted muscle at an earlier postoperative stage.

PMID- 9663545
TI  - Influence of temperature on adenovirus-mediated gene transfer.
AB  - OBJECTIVE: The transfer of recombinant genes to donor organs may allow for novel
      therapeutic approaches to the challenges of acute and chronic rejection.
      Adenoviral vectors are capable of efficient gene transfer, but use of these
      vectors during donor organ preservation may be less efficient due to the low
      temperature. This study was designed to examine the effect of temperature on the
      efficiency of adenovirus-mediated gene transfer. METHODS: Gene transfer to human
      endothelial cells, porcine vascular smooth muscle cells and cultured rat thoracic
      aortas was examined. Incubation with an adenoviral vector encoding for E. coli
      beta-galactosidase was performed for 1 h at three different temperatures: 4
      degrees C, 10 degrees C and 37 degrees C. Transgene expression was assessed by
      histochemical staining for beta-galactosidase in transduced cells and by
      evaluation of beta-galactosidase activity in organ cultures. RESULTS: Both in
      human endothelial cells and vascular smooth muscle cells the percentage of
      positively staining cells following transduction at 37 degrees C was
      significantly greater than at 4 degrees C and at 10 degrees C (30.55 +/- 7.26%
      vs. 14.29 +/- 3.79% and 12.43 +/- 2.47%, respectively for endothelial cells, P <
      0.01 vs. 4 degrees C and 10 degrees C; and 28.25 +/- 4.52% vs. 17.91 +/- 3.76%
      and 16.63 +/- 3.92%, respectively for smooth muscle cells, P < 0.05 vs. 4 degrees
      C, P < 0.01 vs. 10 degrees C). Beta-galactosidase activity was significantly
      greater in aortas transduced at 37 degrees C than in vessels transduced at 4
      degrees C and 10 degrees C (289,700 +/- 113,300 vs. 149,600 +/- 54,390 and
      108,800 +/- 23,140 relative chemiluminesce units/mg of total protein,
      respectively; P < 0.05 vs. 4 degrees C, P < 0.001 vs. 10 degrees C). CONCLUSIONS:
      The present study demonstrates that the efficiency of adenovirus-mediated gene
      transfer is significantly reduced at lower temperatures. The need for cold
      preservation of donor organs may render efficient adenovirus-mediated gene
      transfer more difficult in the transplantation setting.

PMID- 9663546
TI  - Images in cardio-thoracic surgery. Intermittent left-to-right shunt due to a left
      atrial myxoma.

PMID- 9663547
TI  - Combined tracheal resection and aortic valve replacement with a cryopreserved
      aortic valve allograft.
AB  - A 69-year-old patient presented with an association of tracheal squamous cell
      carcinoma and severe aortic valve stenosis. As there was no evidence of
      metastatic spread a potentially curative resection could be considered. The
      patient underwent tracheal resection and aortic valve replacement in a one-stage
      procedure. In light of the potential risk of infection to a prosthetic valve, a
      cryopreserved aortic valve homograft was implanted. The patient made a full
      recovery and is doing well after 2 years of follow-up.

PMID- 9663548
TI  - Gigantic primary lipoma of the diaphragm presenting with respiratory failure.
AB  - Primary diaphragmatic lipomas are rare. A 66-year-old female case is reported,
      with the unusual presentation of progressive dyspnoea leading to respiratory
      failure, mainly because of a large fatty mass occupying the base of the left
      hemithorax. The completely resected mass (16 x 14.5 x 5.5 cm) was a primary
      diaphragmatic lipoma. The literature is discussed. We recommend surgical
      exploration since the possibility of liposarcoma cannot be excluded.

PMID- 9663549
TI  - Cervical bronchogenic cyst mimicking thyroid adenoma.
AB  - Bronchogenic cysts are congenital malformations of the foregut which are
      generally encountered within the mediastinum. We explored a patient presenting
      with a cystic, partially calcified tumor in a cervical and retrotracheal
      location. This lesion was interpreted as a thyroid adenoma preoperatively, but
      identified as a bronchogenic cyst at pathology.

PMID- 9663550
TI  - Pulmonary blastoma.

PMID- 9663551
TI  - Dendritic integration in olfactory sensory neurons: a steady-state analysis of
      how the neuron structure and neuron environment influence the coding of odor
      intensity.
AB  - Response properties of the receptor potential at steady state were analyzed in a
      biophysical model of an olfactory sensory neuron embedded in a multicell
      environment. The neuron structure was described as a set of several identical
      dendrites (or cilia) bearing the transduction mechanisms, joined to a nonsensory
      part--dendritic knob, soma, and axon. The different ionic compositions of the
      media surrounding the neuron sensory and nonsensory parts and the extraneuronal
      voltage sources, which both result from the presence of auxiliary cells, were
      also taken into account. Analytical solutions were found to describe how the
      receptor potential at the nonsensory part responds to a uniform change in the
      odorant-dependent conductance resulting from odorant stimulation of the sensory
      dendrites. We investigated the influence of various geometrical and electrical
      parameters on the receptor-potential response in the classical model neuron
      within a homogeneous environment and in the model neuron surrounded with
      auxiliary cells. First, it was found that the maximum amplitude of the receptor
      potential is independent of the neuron structure in the absence of auxiliary
      cells but not in their presence. In the latter case, the amplitude decreases with
      the length and number of sensory dendrites and with the input resistance of the
      nonsensory part. Second, the sensitivity (as measured by the increase in membrane
      conductance at half-maximum response) of the neuron model in the absence of
      auxiliary cells is higher, but its dynamic range is narrower than in their
      presence. The dynamic range is wide and the sensitivity low when the input
      resistance of the nonsensory part is small and the sensory dendrite is
      unbranched. Both sensitivity and dynamic range are higher for a longer dendrite.
      These results help understand the morphology of insect olfactory sensilla and can
      be generalized to other neuron types.

PMID- 9663552
TI  - Estimation of coupling strength in regenerated lamprey spinal cords based on a
      stochastic phase model.
AB  - We present a simple stochastic model of two coupled phase oscillators and a
      method of fitting the model to experimental spike-train data or to sequences of
      burst times. We apply the method to data from lesioned isolated lamprey spinal
      cords. The remaining tracts at the lesion site are either regenerated medial
      tracts, regenerated lateral tracts, control medial tracts, or control lateral
      tracts. We show that regenerated tracts on average provide significantly weaker
      coupling than control tracts. We compare our model-dependent estimate of coupling
      strength to a measure of coordination based on the size of deflections in the
      spike-train cross-correlation histogram (CCH). Using simulated data, we show that
      our estimates are able to detect changes in coupling strength that do not change
      the size of deflections in the CCH. Our estimates are also more resistant to
      changes in the level of dynamic noise and to changes in relative oscillator
      frequency than is the CCH. In simulations with high levels of dynamic noise and
      in one experimental preparation, we are able detect significant coupling strength
      although there are no significant deflections in the CCH.

PMID- 9663553
TI  - On the use of Bayesian methods for evaluating compartmental neural models.
AB  - Computational modeling is being used increasingly in neuroscience. In deriving
      such models, inference issues such as model selection, model complexity, and
      model comparison must be addressed constantly. In this article we present briefly
      the Bayesian approach to inference. Under a simple set of commonsense axioms,
      there exists essentially a unique way of reasoning under uncertainty by assigning
      a degree of confidence to any hypothesis or model, given the available data and
      prior information. Such degrees of confidence must obey all the rules governing
      probabilities and can be updated accordingly as more data becomes available.
      While the Bayesian methodology can be applied to any type of model, as an example
      we outline its use for an important, and increasingly standard, class of models
      in computational neuroscience--compartmental models of single neurons. Inference
      issues are particularly relevant for these models: their parameter spaces are
      typically very large, neurophysiological and neuroanatomical data are still
      sparse, and probabilistic aspects are often ignored. As a tutorial, we
      demonstrate the Bayesian approach on a class of one-compartment models with
      varying numbers of conductances. We then apply Bayesian methods on a
      compartmental model of a real neuron to determine the optimal amount of noise to
      add to the model to give it a level of spike time variability comparable to that
      found in the real cell.

PMID- 9663554
TI  - Dendritic and synaptic effects in systems of coupled cortical oscillators.
AB  - We explore the influence of synaptic location and form on the behavior of
      networks of coupled cortical oscillators. First, we develop a model of two
      coupled somatic oscillators that includes passive dendritic cables. Using a phase
      model approach, we show that the synchronous solution can change from a stable
      solution to an unstable one as the cable lengthens and the synaptic position
      moves further from the soma. We confirm this prediction using a system of coupled
      compartmental models. We also demonstrate that when the synchronous solution
      becomes unstable, a bifurcation occurs and a pair of asynchronous stable
      solutions appear, causing a phase lag between the cells in the system. Then using
      a variety of coupling functions and different synaptic positions, we show that
      distal connections and broad synaptic time courses encourage phase lags that can
      be reduced, eliminated, or enhanced by the presence of active currents in the
      dendrite. This mechanism may appear in neural systems where proximal connections
      could be used to encourage synchrony, and distal connections and broad synaptic
      time courses could be used to produce phase lags that can be modulated by active
      currents.

PMID- 9663555
TI  - Competitive calcium binding: implications for dendritic calcium signaling.
AB  - Action potentials evoke calcium transients in dendrites of neocortical pyramidal
      neurons with time constants of < 100 ms at physiological temperature. This time
      period may not be sufficient for inflowing calcium ions to equilibrate with all
      present Ca2+-binding molecules. We therefore explored nonequilibrium dynamics of
      Ca2+ binding to numerous Ca2+ reaction partners within a dendritelike compartment
      using numerical simulations. After a brief Ca2+ influx, the reaction partner with
      the fastest Ca2+ binding kinetics initially binds more Ca2+ than predicted from
      chemical equilibrium, while companion reaction partners bind less. This
      difference is consolidated and may result in bypassing of slow reaction partners
      if a Ca2+ clearance mechanism is active. On the other hand, slower reaction
      partners effectively bind Ca2+ during repetitive calcium current pulses or during
      slower Ca2+ influx. Nonequilibrium Ca2+ distribution can further be enhanced
      through strategic placement of the reaction partners within the compartment.
      Using the Ca2+ buffer EGTA as a competitor of fluo-3, we demonstrate competitive
      Ca2+ binding within dendrites experimentally. Nonequilibrium calcium dynamics is
      proposed as a potential mechanism for differential and conditional activation of
      intradendritic targets.

PMID- 9663556
TI  - Presence of links between zinc and melatonin during the circadian cycle in old
      mice: effects on thymic endocrine activity and on the survival.
AB  - Links between zinc and melatonin in old melatonin treated mice with a
      reconstitution of thymic functions have been recently documented. Concomitant
      increments of the nocturnal peaks of zinc and melatonin, with a synchronization
      of their circadian patterns, are achieved in old mice after melatonin treatment.
      A recovery of the nocturnal peaks of thymulin plasma levels and of the number of
      thymulin-secreting cells with a synchronization of their circadian patterns are
      also achieved. The existence of significant positive correlations between
      melatonin and zinc and between melatonin and thymulin or the number of thymulin
      secreting cells supports the presence of links between zinc and melatonin also
      during the circadian cycle with a beneficial effect on thymic functions. The
      altered circadian pattern of corticosteron in old mice is normalized by
      melatonin. The existence of inverse correlations between corticosteron and
      melatonin, between corticosteron and zinc and between corticosteron and thymulin
      or the number of thymulin-secreting cells during the whole circadian cycle,
      suggests the involvement of glucocorticoids pathway in the melatonin thymic
      reconstitution, via zinc. The presence of an interplay among zinc, melatonin,
      glucocorticoids and thymulin may be, therefore, supported during the circadian
      cycle. 'In vitro' experiments from old thymic explants show a direct action of
      zinc, rather than melatonin, on thymulin production, further suggesting that the
      action of melatonin on the thymic efficiency is mediated by the zinc
      bioavailability. The beneficial effect of the links between zinc and melatonin on
      thymic functions during the circadian cycle, may be extended to a prolonged
      survival in aging, where, however, zinc may be more involved.

PMID- 9663557
TI  - A role for natural killer cells in the immunopathogenesis of multiple sclerosis.
AB  - Seventeen relapsing-remitting (R/R) multiple sclerosis (MS) patients and age/sex
      matched controls were studied every 6 weeks for 2 years. Disease activity,
      determined both clinically and by serial MRI, was correlated with natural killer
      (NK) cell functional activity (FA) and phenotype. Mean NK cell FA is
      significantly lower in MS patients, compared to controls (P < 0.001), while
      variability around the means is significantly greater (P < 0.01). The spectrum of
      mean NK cell FA, observed in the patient cohort, along with cyclical nature of
      the FA and phenotype over time, observed in both patients and controls, may begin
      to explain the discrepant results reported in previous studies. In R/R MS, there
      is a significant correlation between reductions (valleys) in NK cell FA and the
      development of active lesions on MRI, new (P < 0.001) or enlarging (P = 0.05).
      More importantly, a significant number of active lesions, new (P = 0.01) and
      enlarging (P = 0.02), are preceded by a reduction in NK cell FA. The correlation
      between the onset of clinical attacks and valleys of NK cell FA is also
      significant (P = 0.002). When taken together, the results suggest that reductions
      (valleys) in NK cell FA represent periods of susceptibility for the development
      of active lesions on MRI and clinical attacks. A significant positive correlation
      is also identified between mean NK cell FA for each R/R MS patient and total
      number of active MRI lesions developed by that patient over the 2 years (P =
      0.001). The results would suggest that R/R MS patients with a higher mean NK cell
      FA are at greater risk for the development of active lesions. These results
      support the proposal that NK cells may play a role in the immunopathogenesis of
      R/R MS.

PMID- 9663558
TI  - Thermogenic and corticosterone responses to intravenous cytokines (IL-1beta and
      TNF-alpha) are attenuated by subdiaphragmatic vagotomy.
AB  - The brain orchestrates changes in behavior and physiology as a consequence of
      peripheral immune activation and infection. These changes require that the brain
      receives signals from the periphery that an immunological challenge has occurred.
      Previous research has established that cytokines play a role in signalling the
      brain. What remains unclear, however, is how peripheral cytokines signal the
      central nervous system. A recent proposal is that cytokines signal the brain by
      stimulating peripheral nerves. The hypothesis states that following infection and
      the release of cytokines such as IL-1beta into local tissue or microvasculature,
      IL-1beta stimulates IL-1 receptors on vagal afferent terminals, or more likely on
      cells of vagal paraganglia. Vagal afferents, in turn, signal the brain. Previous
      work has demonstrated that transection of the vagus below the level of the
      diaphragm blocks or attenuates many illness consequences of intraperitoneally
      (i.p.) administered lipopolysaccharide (LPS) or IL-1beta. The present studies
      extend these findings by examining the effect of subdiaphragmatic vagotomy on
      illness consequences following intravenously (i.v.) administered IL-1beta and TNF
      alpha. Subdiaphragmatic vagotomy attenuated both the fever response and
      corticosterone response produced by i.v. administered cytokines. This effect was
      dose dependent. The results add support to the hypothesis that vagal afferents
      are involved in peripheral cytokine-to-brain communication.

PMID- 9663559
TI  - Interleukin-10 reduces the endotoxin-induced hyperalgesia in mice.
AB  - In the endotoxin-induced inflammation, interleukin-10 reduced significantly, and
      in a dose-dependent manner, the inflammatory pain as assessed by mechanical and
      thermal tests. The levels of Tumour Necrosis Factor (TNF)alpha and NGF were
      upregulated at 1.5 h whereas those of IL-1beta at 6 h after ET injection. IL-10
      downregulated the levels of TNFalpha (from 4974.75 +/- 875.78 to 1008 +/- 350
      pg/hind paw), NGF (from 352.9 +/- 46.7 to 33.9 +/- 2.4 pg/hind paw) and IL-1beta
      (from 2773.88 +/- 423.96 to 1108 +/- 399.56 pg/hind paw). These data suggest that
      IL-10 inhibits ET-induced hyperalgesia by downregulation of TNFalpha, IL-1beta
      and NGF production.

PMID- 9663560
TI  - Serum CD95 of relapsing remitting multiple sclerosis patients protects from CD95
      mediated apoptosis.
AB  - Failure of CD95-mediated apoptosis as a potential negative regulatory mechanism
      of T cell expansion may be involved in T cell-mediated autoimmune diseases such
      as multiple sclerosis (MS). Recently, soluble CD95 has been shown to be elevated
      in MS patients with active disease. Here, we report that the sera of MS patients
      inhibit CD95 ligand-induced apoptosis of susceptible target cells in a
      concentration-dependent manner and dependent on the amount of serum CD95 levels.
      Thus, MS sera contain biologically active inhibitors of T cell apoptosis that may
      allow for prolonged abnormal immune responses.

PMID- 9663561
TI  - Interferon-beta inhibits mitogen induced astrocyte proliferation in vitro.
AB  - The central nervous system response to injury and inflammation commonly includes
      astrocytosis. This process, which is manifest by astrocyte hypertrophy and
      proliferation, is particularly prominent in multiple sclerosis (MS), where in
      chronic lesions it may contribute to the lack of repair by restricting the
      migration of remyelinating cells. Interferon-beta (IFN-beta) modestly reduces the
      frequency of relapses in MS and may have a small effect on the accumulation of
      permanent disability. Here, we show that IFN-beta inhibits the in vitro
      proliferative response of rodent astrocytes to a wide variety of growth factors
      and cytokines. Although important species differences exist in these glial
      responses this previously unrecognised property of IFN-beta may have implications
      for reducing astrocytosis and thereby promoting endogenous repair.

PMID- 9663562
TI  - The immune system can affect learning: chronic immune complex disease in a rat
      model.
AB  - Evidence is presented that the immune system can affect central nervous system
      functioning, leading to changes in learning. Immune complex disease is induced in
      rats and their behavior tested using a Lashley maze. Significant differences in
      behavior were found between the animals with high disease activity and those with
      low disease activity and the non-disease controls. These changes were not due to
      uremia and are most likely due to the immune response. There is some evidence
      immune complex deposits in the choroid plexus may play some role, but not the
      sole or major role in the behavioral changes. This provides a model by which
      immunologic processes can cause neuropsychiatric manifestations in autoimmune
      diseases like lupus, as well as showing that immune processes can affect
      behavioral functioning.

PMID- 9663563
TI  - Effect of macrophage depletion by liposomes containing dichloromethylene
      diphosphonate on endotoxin-induced uveitis.
AB  - Footpad injection of lipopolysaccharide (LPS) from Salmonella typhimurium in
      Lewis rats induces an acute anterior and posterior endotoxin-induced uveitis
      (EIU). To investigate the role of macrophages in the pathogenesis of EIU, we
      eliminated macrophages by means of liposomes containing dichloromethylene
      diphosphonate (Cl2MDP), a drug which depletes macrophages but not other
      immunocompetent cells. Intravenous injection of CL2MDP-liposomes clearly
      inhibited clinical and histological manifestations of uveitis in the anterior
      segment of the eye (iris/ciliary body) and reduced TNF level in aqueous humor.
      Specific immunostaining showed that CL2MDP-liposome injections decreased the
      number of ED2 + resident macrophages in the iris/ciliary body and the choroid.
      After LPS injection, CL2MDP-liposome treatment reduced the density of
      infiltrating ED1 + cells (mainly monocytes/macrophages) in the iris/ciliary body
      but not in the choroid; little or no effect was detected on the OX42 + cellular
      infiltration (mainly polymorphonuclear leukocytes). The inflammatory cellular
      infiltration of the retina was not modified by the treatment. These findings
      suggest that macrophages play a key role in the pathogenesis of ocular
      inflammation.

PMID- 9663564
TI  - Catecholamines and lipopolysaccharide synergistically induce the release of
      interleukin-6 from thymic epithelial cells.
AB  - The thymus as the major site of T-cell development is exposed to circulating
      hormones as well as to neurotransmitters released from peripheral nerves. We
      investigated the influence of catecholamines on the synthesis of interleukin-1
      (IL-1) and IL-6 by cultured rat thymic epithelial cells. Basal or
      lipopolysaccharide (LPS)-stimulated production of IL-1 was not affected by
      catecholamines. Release of IL-6 was stimulated only scarcely by catecholamines or
      tumor necrosis factor-alpha (TNF-alpha) and moderately by LPS alone. However, co
      stimulation with adrenaline, noradrenaline, or the beta-adrenoceptor agonist
      isoproterenol (isoprenaline) had an additive (TNF-alpha) or synergistic (LPS)
      effect on IL-6 release. The synergistic effect was dose-dependent on
      catecholamine or LPS concentrations. It was mediated by beta-adrenoceptors that
      are linked to elevation of intracellular cAMP levels, since it was promoted by
      beta-adrenoceptor agonists and could be blocked by beta-adrenoceptor antagonists.
      Co-incubation of LPS with agents directly raising cAMP-levels like forskolin or
      dibutyryl cAMP yielded even stronger IL-6 induction. After co-stimulation IL-6
      mRNA was first detected after 3-4 h and a constant increase of IL-6 bioactivity
      in the culture supernatant was measured for up to 48 h. Since IL-6 is an
      important factor for thymocyte differentiation and proliferation, the findings
      demonstrate an influence of neuronal or hormonal catecholamines on the thymic
      microenvironment that is created by thymic epithelial cells.

PMID- 9663565
TI  - Specific binding of melatonin by purified cell nuclei from spleen and thymus of
      the rat.
AB  - In the present paper, we show that pineal hormone melatonin interacts with
      purified cell nuclei from rat spleen and thymus. Binding of 2-[125I]iodomelatonin
      ([125I]melatonin) by cell nuclei fulfills all criteria for binding to a receptor
      site. Binding exhibited properties such as dependence on time and temperature as
      well as reversibility, saturability, high affinity, and specificity. Results
      suggested binding to single classes of binding sites. The dissociation constants
      (Kd) for the binding sites in the spleen and thymus nuclei were 68 and 102 pM,
      respectively. These data are in close agreement with data obtained from kinetic
      studies, in which the kinetically derived values of the dissociation constant in
      the spleen and thymus nuclei were 166 and 537 pM, respectively. The affinities
      for melatonin of these nuclear binding sites suggest that they may recognize the
      physiological concentrations of melatonin in the tissues. Finally, we have
      demonstrated that binding of [125I]melatonin by the nuclei is displaced by CGP
      52608, a specific ligand of the putative nuclear melatonin receptor RZR/ROR.
      Results strongly suggest that in addition to membrane receptor-related
      mechanisms, nuclear receptors may be involved in the regulation of immune system
      by melatonin.

PMID- 9663566
TI  - Increased Fas-mediated cytotoxicity of CD4-positive T cells in patients with
      human T-lymphotropic virus type I-associated myelopathy.
AB  - Using a 51Cr release assay, we investigated Fas-mediated cytotoxicity of
      peripheral blood CD4+ T cells of patients with human T-lymphotropic virus type-I
      (HTLV-I)-associated myelopathy (HAM) against T98G, a glioblastoma cell line which
      expresses Fas. Cytotoxic activity of CD4+ T cells against T98G was significantly
      higher in HAM patients than in controls. Moreover, when CD4+ T cells of HAM
      patients were preincubated with a monoclonal antibody to human Fas ligand (FasL),
      cytotoxic activity against T98G was significantly suppressed. These results
      suggest that damage to nervous tissues by the Fas/FasL system is involved in the
      pathogenesis of HAM.

PMID- 9663567
TI  - Role of interferon-gamma in the pathogenesis of LCMV-induced meningitis:
      unimpaired leucocyte recruitment, but deficient macrophage activation in
      interferon-gamma knock-out mice.
AB  - Generally, interferon-gamma (IFN-gamma) is considered a critical regulator of T
      cell mediated inflammation. For this reason, we investigated the pathogenesis of
      lymphocytic choriomeningitis in mice with a targeted defect of the gene encoding
      this cytokine. Our results revealed that IFN-gamma is redundant in the afferent
      phase of the antiviral T cell response as well as a local mediator of this T cell
      mediated inflammatory disease. However, IFN-gamma may play an indirect role as it
      is involved in reducing extraneural infection that may compete with CNS for
      available effector cells. Analysis of the inflammatory exudate disclosed that
      leucocyte recruitment was unimpaired in the absence of IFN-gamma as was the
      upregulation of ICAM-1 and VCAM-1 on endothelium at the inflammatory site.
      However, local macrophage activation (production of tumor necrosis-alpha and NO)
      was significantly impaired. Notably, a viral peptide could also elicit a T cell
      mediated inflammatory response in virus-primed IFN-gamma knock-out mice,
      indicating that redundancy of this cytokine as a proinflammatory mediator is not
      restricted to inflammatory reactions triggered by an active infection. Thus, T
      cell mediated inflammation may be induced in the absence of IFN-gamma and local
      macrophage activation.

PMID- 9663568
TI  - Immunopathology of multiple sclerosis: report on an international meeting held at
      the Institute of Neurology of the University of Vienna.

PMID- 9663569
TI  - A new focus on focal infection.

PMID- 9663570
TI  - Surgical treatment of squamous cell carcinoma of the lower lip: evaluation of
      long-term results and prognostic factors--a retrospective analysis of 184
      patients.
AB  - PURPOSE: A retrospective study was undertaken to evaluate the results of surgical
      treatment of primary squamous cell carcinoma of the vermilion border of the lower
      lip and to identify parameters of the primary tumor that may predict local
      recurrence and regional metastasis. PATIENTS AND METHODS: From 1979 through 1992,
      184 consecutive patients with a primary squamous cell carcinoma of the lower lip
      underwent surgical excision as a primary treatment. There were 166 (90.2%) men
      and 18 (9.8%) women, with a mean age of 66 years. Most cases (92.9%) were stage I
      tumors. Most of the tumors were well and moderately differentiated squamous cell
      carcinomas (93.5%). Minimal follow-up was 2 years, with a mean of 56 months.
      Disease control was achieved in 165 (89.7%) patients. Local recurrence and
      regional metastasis occurred in 9 (4.9%) and 10 (5.4%) patients, respectively.
      Local failures were treated successfully by either surgery or radiation therapy.
      Regional metastases were treated in nine patients by neck dissection, followed in
      eight cases by radiation therapy. One patient developed distant metastasis.
      RESULTS: Five- and 10-year overall survival rates were 78% and 61%, respectively,
      whereas the disease-free survival rates at 5 and 10 years were 86% and 81%,
      respectively. Multivariate analysis indicated that local recurrence was
      significantly associated with large tumor size and surgical margins containing
      squamous cell carcinoma. Increasing tumor thickness, an infiltrative invasion
      pattern, and perineural invasion were significant prognostic indicators of
      regional metastasis. CONCLUSION: Surgical treatment for small squamous cell
      carcinomas of the lower lip has a favorable prognosis. Particular parameters of
      the primary tumor seem to predict the chance of development of local recurrence
      and regional lymph node metastasis.

PMID- 9663571
TI  - Sensory abnormalities associated with mandibular fractures: incidence and natural
      history.
AB  - PURPOSE: The aims of this study were to determine the incidence of inferior
      alveolar nerve (IAN) abnormalities in patients with mandibular fractures and to
      document the natural history and spontaneous recovery rate in patients with a
      sensory disturbance. PATIENTS AND METHODS: This was a retrospective evaluation of
      patients (n = 150) with mandibular fractures at risk for IAN injury admitted to
      the Oral and Maxillofacial Surgery Service between 1985 and 1995. The inclusion
      criteria were: 1) fractures between the mandibular and mental foramina, 2)
      availability of the results of a post-injury, preoperative sensory examination,
      and 3) at least 1 year follow-up. Fracture characteristics, physical examination
      findings, hospital course, operative treatment, and follow-up were documented.
      Patient interviews were conducted to determine the incidence of long-term sensory
      disturbance and associated morbidity. The results were evaluated with chi-square
      analysis. RESULTS: Fifty-six percent of patients (84 of 150) had a post
      injury/pretreatment IAN abnormality. Patients with sensory disturbance had a
      significantly higher frequency of displaced fractures than those without sensory
      disturbance (P < .001). Sixteen of 24 patients (66.7%) with an abnormal post
      injury/ pretreatment sensory examination reported a permanent sensory deficit
      (mean follow-up, 74.3 months); 55% of these patients complained of impairment.
      CONCLUSIONS: The incidence of postinjury IAN deficits in patients with mandibular
      fractures was greater than 50% and was related to fracture displacement. One
      third of these patients regained normal sensation; the remaining two thirds
      reported a persistent sensory deficit. A significant number of these patients
      complained of discomfort and impairment after a mean follow-up of greater than 6
      years.

PMID- 9663572
TI  - Clinical evaluation and surgical management of congenital preauricular fistulas.
AB  - PURPOSE: The retrospective investigation evaluated the clinical data on patients
      with a preauricular fistula with respect to demographic factors, symptoms,
      preoperative diagnosis, and surgical therapy. Follow-up studies served to
      critically assess the outcome of the operations. PATIENTS AND METHODS: The
      records of 62 patients were studied. Patients were divided into two groups: those
      operated on for the first time for a preauricular fistula and those operated on
      for a recurrence. Controlled follow-up was performed by means of a standardized
      questionnaire filled out by both the patients' physicians and the patients
      themselves. RESULTS: The mean age of patients operated on for the first time was
      16 years, and that of patients operated on for a recurrence was 22 years.
      Although the overall rate of recurrence was 21%, it differed widely between
      groups (14% in first operations and 42% in patients operated on for the first
      time for a recurrence). These figures are within the lower range of the
      recurrence rates previously reported. Serious side effects, such as persistent
      damage to the facial nerve, were not observed. CONCLUSIONS: Operative management
      of a preauricular fistula is a treatment with few side effects that should be
      offered to each patient with such a malformation. Because the first operation is
      decisive for the further course of the condition, surgery should be performed
      under optimum conditions to avoid recurrence.

PMID- 9663573
TI  - A comparison between TNM and TANIS stage grouping for predicting prognosis of
      oral and oropharyngeal cancer.
AB  - PURPOSE: The 1987 TNM classification system modified some T and N definition but
      it did not change stage grouping. Consequently it has not improved the prognostic
      validity of the advanced stage groups. In 1993, a new stage grouping was
      purposed, TANIS, that seems to have a higher correlation with survival. In this
      report, the TNM classification and TANIS system were compared to evaluate this
      prognostic ability. PATIENTS AND METHODS: Data from 164 patients affected by
      primary cancers of oropharynx or oral cavity were analyzed by means of Kaplan
      Meier and Cox regression analysis. RESULTS: The crude survival rate at 5 years
      was 43.9%. Both systems showed a significant correlation with the survival rate
      by means of Cox regression analysis. TANIS subcategories were correlated to the
      mortality rate in the stage IV patients. TANIS resulted a better predictor of
      mortality when compared with TNM. CONCLUSION: The TANIS system was able to
      separate the TNM stage IV patients into prognostic groups, yielding more
      information with respect to TNM for such a category of patients. When a
      comparison between TNM and TANIS was performed, it was observed that TANIS had a
      higher correlation with survival rate, whereas TNM did not add any information in
      defining the survival function.

PMID- 9663574
TI  - Management of animal bite injuries of the face: experience with 94 patients.
AB  - PURPOSE: Because of the large number of bacteria in the oral cavity, animal bite
      wounds are generally contaminated, and their treatment is difficult because of
      the risk of infection, especially in extensive injuries. This report describes
      the management of a large series of patients and recommends treatment guidelines
      on the basis of the results. PATIENTS AND METHODS: Ninety-four animal bite wounds
      on the face and head were analyzed according to the type of animal, location and
      extent of the soft tissue wound, duration and type of surgical treatment,
      occurrence of infections and their pathogen spectrum, as well as the choice of
      antibiotic therapy. RESULTS: Dogs caused 91% of the bite wounds. Infections
      developed in 4 of 53 patients who underwent primary wound closure with minor edge
      excision and prophylactic administration of oral penicillin. Without antibiotic
      administration, 2 of 15 patients had infections, which were treated on an
      outpatient basis. Of 26 patients with initially delayed treatment, 18 showed
      clinical inflammatory symptoms with a wide spectrum of pathogens (Escherichia
      coli, Streptococcus, Enterococcus, Staphylococcus epidermidis, and Proteus) on
      presentation. CONCLUSION: Extensive animal bite wounds on the face, even with
      soft tissue defects, should be treated according to the criteria of a esthetic
      reconstructive facial surgery. In view of the low infection rate, routine
      antibiotic prophylaxis is not justified.

PMID- 9663575
TI  - Effects of postoperative external beam irradiation after carotid artery stripping
      of nodal metastasis.
AB  - PURPOSE: The objective of this study was to determine the effects of
      postoperative external beam irradiation (PEBI) on patients after stripping the
      carotid vessel of nodal metastasis. PATIENTS AND METHODS: Of 245 patients who
      underwent radical neck dissection for cancer of the upper aerodigestive tract
      between 1981 and 1995, 13 patients with nodal metastasis adherent to the carotid
      artery (NMCA) received a full course of PEBI after the tumor was peeled off the
      carotid vessel. Patterns of treatment failure, survival, and serious morbidity
      were evaluated. RESULTS: At the time of last follow-up (range, 3 to 125 months),
      fewer than half of the patients (46%) were free of disease, and two patients
      (15%) had developed distant metastases. The estimated 2-year survival rate was
      23%. There were no intraoperative, postoperative, or post-radiation therapy
      complications. CONCLUSION: PEBI after carotid artery stripping of tumor can
      achieve locoregional disease control in select patients without an increased risk
      of vessel rupture. However, if the prognosis for patients with NMCA is to
      improve, other effective management strategies need to be investigated.

PMID- 9663576
TI  - Changes in bite force and occlusal contacts in patients treated for mandibular
      prognathism by orthognathic surgery.
AB  - PURPOSE: The purpose of this study was to evaluate changes in bite force and
      occlusal contacts before and after orthognathic surgery in patients with
      mandibular prognathism and to compare the findings with those in controls with
      normal occlusion. PATIENTS AND METHODS: Bite force and occlusal contacts were
      analyzed in 23 (7 male and 16 female) patients with mandibular prognathism before
      and after sagittal split ramus osteotomy, and in 20 (10 male and 10 female)
      controls with normal occlusion. The bite force and occlusal contacts were
      simultaneously measured by a computerized occlusal analysis system, the T-Scan
      system, immediately before surgery, and at 6 weeks, 3 months, 6 months, and 1
      year postoperatively. RESULTS: Both the bite force and occlusal contacts in the
      patients were significantly less than those in the controls before surgery.
      Although both the bite force and occlusal contacts in the patients were improved
      by the orthognathic surgery, neither approached the level in the controls within
      1 year. Bite force was correlated with the number of occlusal contacts in both
      patient and control groups. CONCLUSION: The postoperative masticatory function
      does not reach control levels even 1 year after the orthognathic surgery for
      mandibular prognathism. Therefore, further adjustment of the occlusion should be
      considered before the end of treatment.

PMID- 9663577
TI  - Healing response to various forms of human demineralized bone matrix in athymic
      rat cranial defects.
AB  - PURPOSE: This study compared the ability of a bone autograft and four distinct
      forms of human demineralized bone (DBM) to elicit bone repair in a critical size
      cranial defect in athymic rats. MATERIALS AND METHODS: Cranial defects were
      created in athymic rats and then grafted with either an autograft, rat DBM
      particles in glycerol (rGel), or one of four forms of human DBM: 1) hGel; 2)
      Putty (DBM fibers in glycerol); 3) Sheet (sheet of DBM fibers); or 4) Flex (DBM
      fiber sheet with glycerol). Histology, histomorphometry, and radiographic density
      of the graft sites were evaluated at 8 weeks. RESULTS: Of the grafted defects,
      29% to 58% were found to be filled with new bone. The rGel and human forms of DBM
      stimulated similar amounts of new bone growth in comparison with the autograft
      filled defects. The fiber-based grafts produced the largest amounts of new bone.
      CONCLUSIONS: Human DBM in gel, putty and sheet forms were found to perform as
      well as an autograft in a critical size cranial defect in the athymic rat.

PMID- 9663578
TI  - Rapidly growing, expansile mass of the mandible in a 6-year-old boy.

PMID- 9663579
TI  - The possible role of nitric oxide in the physiopathology of pain associated with
      temporomandibular joint disorders.
AB  - Temporomandibular joint disorders (TMD) pose a significant challenge to the
      practice of oral and maxillofacial surgery. When painful, TMD are generally
      associated with hyperthermia of the overlying skin. It is hypothesized that this
      skin hyperthermia, caused by regional vasodilation, is induced by nitric oxide
      (NO) produced in the extravascular space of the joint. Extravascular NO can be
      produced by osteoblasts, chondrocytes and macrophages, or by stimulated neurons.
      It is suggested that this kind of pain is associated with NO-enhanced sensitivity
      of the peripheral nociceptors. Verification and clinical implications of the
      proposed mechanism are discussed.

PMID- 9663580
TI  - Unilateral hypertrophy of the face associated with infiltrating lipomatosis.

PMID- 9663581
TI  - A macular hole after maxillofacial trauma: report of a case.

PMID- 9663582
TI  - Synovial chondrosarcoma arising in the temporomandibular joint.

PMID- 9663583
TI  - Caliber-persistent artery of the lip: case report.

PMID- 9663584
TI  - Pulmonary chondroid hamartoma: an incidental finding in a case of tongue
      carcinoma.

PMID- 9663585
TI  - Not seeing eye-to-eye about septal grafts for orbital fractures.

PMID- 9663586
TI  - Keeping the record straight.

PMID- 9663587
TI  - Needle placement for arthrocentesis.

PMID- 9663588
TI  - Classic Kaposi's sarcoma in Arabs living in Israel, 1970-1993: a population-based
      incidence study.
AB  - The incidence of classic Kaposi's sarcoma (CKS) has been reported to be high in
      Jewish populations living in Israel and in immigrants originating from the
      Mediterranean basin. No population-based reports are available on the incidence
      of CKS in Israeli Arabs. We analyzed the incidence of CKS cases occurring between
      1970 and 1993 among Arabs living in Israel. Reporting systems were the Israel
      Cancer Registry, the medical documentation of all-Kaposi's sarcoma cases and the
      registry of human immunodeficiency virus-seropositive patients. Population
      figures were derived for census surveys (1972 and 1983) and inter-census data
      based on annual updating of demographic characteristics. Age-standardized
      incidence rates (ASR) were 6.87 per million in men and 2.18 per million in women.
      The ASR did not increase between 1970 and 1993 in either men or women. The age
      adjusted male to female ratio was 2.0 below 50 years of age and 3.5 above it. The
      observation of a stable and relatively high incidence of CKS in Israel-born
      Arabs, comparable to other populations living in the Mediterranean basin,
      suggests that risk is related to geographical origin. CKS incidence, however, is
      lower than that in Israel-born Jews.

PMID- 9663589
TI  - The cure for colon cancer: results from the EUROCARE study.
AB  - The interpretation of time trends and geographical differences of population
      based survival rates is generally not easy, due to the difficulty in
      disentangling the effects of observational biases, diagnostic and therapeutic
      procedures and their interactions. Whereas descriptive analysis of relative
      survival is generally based on survival levels estimated at fixed time since
      diagnosis, interpretation issues can take advantage from the analysis of the
      shape of the considered relative survival. Parametric survival models allowing
      the estimation of the fraction of cured patients are applied here to analyze and
      discuss the differences in colon cancer relative survival between European
      countries, according to age and period of diagnosis. The survival curves of colon
      cancer patients are described according to 2 parameters: the proportion of cured
      patients and the mean survival time of fatal cases. These parameters are
      estimated by least square nonlinear regression of relative survival values
      derived from the EUROCARE Project publication. Exponential and Weibull survival
      functions are used to model the relative survival curve for the fraction of fatal
      cases. The Weibull model gives generally a better fit with respect to the
      exponential model, thus indicating that the mortality rate for fatal cases is
      decreasing with time since diagnosis. For the youngest patients, however, the 2
      survival functions give practically overlapping estimates. The overall proportion
      of colon cancer patients in Europe that are estimated to be cured was 38.6%. This
      proportion increased from 36% to 40% for patients diagnosed in 1978-1980 and in
      1983-1985, respectively. Accordingly, mean survival time of fatal cases increased
      from 1.18 to 1.52 years. According to age, the proportion of cured patients
      present a marked decrease from young (48.4% at age 15-44 years) to middle-aged
      patients (38.6% at age 5564 years) and only a mild decrease from these to the
      oldest patients (34.4% at age 75 or more). The opposite effect was shown by
      survival time of fatal cases, i.e., 1.71, 1.75 and 0.77 years for the same age
      classes, respectively. Proportion of cured cases and mean survival time of fatal
      cases tended to be positively correlated with each other across countries. Our
      results are consistent with the hypothesis that a real improvement in colon
      cancer survival took place in Europe during the years 1978-1985 and also suggest
      that the well-known decrease of relative survival with age at diagnosis could be
      mostly due to a decreasing efficacy of early diagnosis for patients under 60
      years old and to less effective therapies for older patients.

PMID- 9663590
TI  - Parity, age at first birth and the risk of carcinoma in situ of the breast.
AB  - Epidemiological studies of in situ breast cancer are sparse, and the role of
      reproductive history, an established risk modifier for invasive breast cancer,
      remains incompletely investigated. To examine possible associations with parity
      and age at first birth, we undertook a case-control study nested in a nationwide
      cohort of Swedish women. The reproductive history of 1,368 women aged 65 or
      younger with a diagnosis of carcinoma in situ of the breast were compared with
      that of 6,837 age-matched controls drawn randomly from a population-based
      Fertility Registry. Statistical analyses were performed by conditional logistic
      regression. Compared to nulliparous women, ever-parous women were at a reduced
      risk of carcinoma in situ of the breast. The risk decreased with number of live
      births, with the estimated risk reduction in the highest parity group (5+), being
      of the same magnitude as that reported for invasive breast cancer. By contrast, a
      positive association with increasing age at first birth was somewhat less
      pronounced than that observed previously in the same data set with respect to
      invasive breast cancer. Our findings indicate that parity affects the risk of
      invasive breast cancer and carcinoma in situ similarly, whereas the effect of age
      at first birth appears to be weaker for the risk of carcinoma in situ.

PMID- 9663591
TI  - The role of alcohol in non-smokers and tobacco in non-drinkers in the aetiology
      of oral epithelial dysplasia.
AB  - Oral epithelial dysplasia (OED) is an important risk factor in predicting
      subsequent development of invasive carcinoma. Despite the malignant potential of
      OED, the current state of knowledge regarding aetiological risk factors
      associated with OED is limited. The aim of our study was to evaluate the
      aetiological role of alcohol consumption in non-tobacco smokers and smoking
      behaviour in non-drinkers, in patients presenting with OED. Data from a hospital
      based case-control study of OED were used to analyse the risk associated with
      alcohol in non-smokers and with tobacco in non-drinkers. A total of 140 cases and
      236 controls were included. In the non-drinkers, the risks of OED increased with
      tobacco smoking of more than 20 cigarettes per day, particularly non-filter
      cigarettes. The risk of OED declined following smoking cessation, with ex-smokers
      of 10 or more years demonstrating no excess risk relative to non-smokers. In the
      nonsmokers, consumption of alcohol was not a significant predictor of OED.
      However, there was a synergistic effect of alcohol when combined with some
      aspects of tobacco smoking. Our results confirm that tobacco has an independent
      role in the aetiology of OED. The role of alcohol, however, is principally only
      important in conjunction with tobacco use.

PMID- 9663592
TI  - Germline mutations in the vhl gene in patients presenting with
      phaeochromocytomas.
AB  - It has been shown that an appreciable percentage of patients presenting with
      primary, apparently sporadic phaeochromocytomas may in fact have von-Hippel
      Lindau (VHL) disease. In order to investigate this, we retrospectively screened
      68 patients, who had been operated on for phaeochromocytomas, for the presence of
      germline mutations in the vhl gene. DNA was isolated from peripheral-blood
      leukocytes and used to screen the entire coding sequence and the intron-exon
      boundaries of the vhl gene for mutations, using a PCR-based SSCP strategy. When
      an abnormal pattern was found in the SSCP analysis, sequence analysis was carried
      out. We found SSC variants in the vhl gene in 8 of the 68 patients. Of 6
      patients, 2 turned out to be related (an uncle and his nephew), and they carried
      the same mis-sense mutation: R64P. In 4 other patients, mis-sense mutations,
      P25L, L63P, G144Q and I147T, were also identified. None of these mutations has
      been described, and 3 of them (P25L, L63P and R64P) are located closer to the N
      terminus of the vhl protein than any reported vhl mutation. In the remaining 2
      cases, the mutations were localized not in the coding sequence but in the
      intronic sequence (but not within splice-sites), adjacent to the exon, so they
      were probably not related to the disease. Our results show that a relatively high
      proportion (6/68, or 8.8%), though not as high as the 20% reported earlier, of
      patients with apparently sporadic phaeochromocytomas may carry germline mutations
      in the vhl gene.

PMID- 9663593
TI  - Oral snuff, smoking habits and alcohol consumption in relation to oral cancer in
      a Swedish case-control study.
AB  - The use of oral snuff is a widespread habit in Sweden. We investigated whether
      the use of Swedish moist snuff leads to an increasing risk of oral cancer. Other
      risk factors such as smoking tobacco and alcoholic beverages were also
      investigated. Our study comprised 410 patients with oral cancer, from the period
      1980-1989, and 410 matched controls. All subjects received a mailed
      questionnaire. The response rates were 96% and 91% for cases and controls,
      respectively. In the study, a total of 20% of all subjects, cases and controls,
      were active or ex-snuff users. The univariate analysis did not show any increased
      risk [odds ratio (OR) 0.7, 95% confidence interval (CI) 0.4-1.1] for active snuff
      users. We found an increased risk (OR 1.8, CI 1.1-2.7) for oral cancer among
      active smokers. Alcohol consumption showed the strongest risk for oral cancer.
      Among consumers of beer, an increased risk of 1.9 (CI 0.9-3.9) was found.
      Corresponding ORs for wine and liquor were 1.3 (CI 0.9-1.8) and 1.6 (CI 1.1-2.3),
      respectively. A dose-response effect was observed. Although not statistically
      significant, a multivariate analysis similarly suggested that the most important
      risk factors were beer and liquor consumption, followed by smoking.

PMID- 9663594
TI  - Case-control study of sun exposure and squamous cell carcinoma of the skin.
AB  - We conducted a case-control study of sun exposure and squamous cell carcinoma
      (SCC) of the skin within a population-based, longitudinal study of skin cancer.
      Cases had histopathologically confirmed SCC. Subjects were interviewed about
      their lifetime sun exposure, including exposure to the site of the SCC (sites for
      controls were assigned randomly). Analysis was restricted to 132 cases and 1,031
      controls born in Australia and with no ancestors from southern Europe. The total
      site-specific exposure was strongly related to risk of SCC; the odds ratio
      increased to a maximum of 3.3 at 65,000 hr of exposure before falling slightly.
      Site-specific exposure during childhood and adolescence was more strongly
      associated with SCC than exposure during adulthood. An intermittent pattern of
      weekly sun exposure was not associated with SCC and the odds ratios for hours of
      exposure on vacation were close to unity. The number of blistering sunburns to
      the site was positively associated with SCC. Use of sunscreens and hats showed
      inconsistent effects. Sun exposure, especially during childhood and adolescence,
      increases the risk of SCC. The pattern of exposure appears to be unimportant,
      despite the association with sunburn, which may simply be an indicator of the
      skin's sensitivity to sunlight.

PMID- 9663595
TI  - BRCA1-related breast cancer in Austrian breast and ovarian cancer families:
      specific BRCA1 mutations and pathological characteristics.
AB  - We identified 17 BRCA1 mutations in 86 Austrian breast and ovarian cancer
      families (20%) that were screened for mutations by denaturing high-performance
      liquid chromatography (DHPLC) and the protein truncation test (PTT). Eleven
      distinct mutations were detected, 4 of them (962del4, 2795del4, 3135del4 and
      L3376stop) not previously reported in families of non-Austrian origin. In
      addition, 6 rare missense mutations (allele frequency < 1%) with unknown
      biological effects were identified. Four mutations occurred more than once in the
      Austrian population: 2795del4 (3 times), Cys61Gly (3 times) 5382insC (2 times)
      and Q1806stop (2 times). Haplotype analysis of the 4 recurrent mutations
      suggested a common ancestor for each of these. Thirty-four breast cancer cases
      from 17 families with BRCA1 mutations were further analyzed. We observed a low
      median age of onset (39.5 years). Sixty-eight percent of all BRCA1 breast cancer
      cases had negative axillary lymph nodes. This group showed a significant
      prevalence of a negative estrogen and progesterone receptor status and stage I
      tumors compared with an age-related, node-negative control group. The prevalence
      of grade III tumors was marginally significant. Survival analysis either with a
      control group matched for age (within 5 years), grade, histologic subtype and
      estrogen receptor status, or with an age-related, node-negative comparison group,
      showed no statistical difference.

PMID- 9663596
TI  - Prevalence and determinants of anti-lytic and anti-latent antibodies to human
      herpesvirus-8 among Italian individuals at risk of sexually and parenterally
      transmitted infections.
AB  - Three hundred seventy-nine individuals [137 non-injecting drug using (non-IDU)
      heterosexuals, 130 homosexual men and 112 IDU] attending the human
      immunodeficiency virus (HIV) testing program of a sexually transmitted disease
      (STD) clinic in Rome were studied to estimate the prevalence and to identify the
      modalities of transmission of human herpesvirus-8 (HHV-8) infection. Serological
      analysis was performed by using an immunofluorescence assay able to detect anti
      latent and anti-lytic HHV-8 antibodies. Twelve acquired immunodeficiency syndrome
      (AIDS)-Kaposi's sarcoma (KS) patients and 94 blood donors were tested as
      reference population groups. Anti-lytic antibodies were detected in 185 (48.8%)
      individuals; 52 of them (13.7%) also had anti-latent antibodies. Both anti-lytic
      and anti-latent antibody prevalence were higher among homosexual men (66.9% and
      27.7%, respectively) than among IDU (49.1% and 8.0%, respectively) and non-IDU
      heterosexuals (31.4% and 5.1%, respectively), and tended to increase with age.
      Anti-lytic HHV-8 antibodies were associated with syphilis [odds ratio (OR)=3.81]
      but not with hepatitis C virus (HCV) seropositivity. HIV-infected homosexual men
      were more likely to have HHV-8 antibodies than those who were HIV-negative. When
      using anti-latent antibodies the direction of the OR remained the same, although
      the associations did not often reach statistical significance. Among AIDS-KS
      patients, 83.3% had anti-lytic and 66.6% had anti-latent antibodies. Among blood
      donors, 28% had anti-lytic antibodies and 2 of them (2.1%) also had anti-latent
      antibodies. Our data indicate that HHV-8 seroprevalence increases with age and is
      higher among homosexual men, particularly those infected with HIV. This is
      consistent with sexual transmission of HHV-8 infection. In addition, the presence
      of HHV-8 antibodies in HIV-negative non-IDU heterosexual contacts and in healthy
      blood donors is consistent with the high incidence of classic KS in Italy.

PMID- 9663597
TI  - Somatically acquired genetic alterations in flat colorectal neoplasias.
AB  - Somatically acquired mutations in several genes have been reported as playing an
      important role during colorectal tumorigenesis. Two alternative groups of
      carcinomas, termed LOH+ and RER+, have been defined on the basis of their genetic
      anomalies, a biallelic inactivation of the APC or the TGF-betaRII genes,
      occurring as an alternative, in LOH+ or RER+ tumors. It is a generally accepted
      hypothesis that most of colorectal cancers (CRC) develop from a pre-existing
      adenomatous polyp. Such benign lesions are usually exophytic polyps, a small
      proportion of adenomas having been described as flat lesions. The latter
      histological category has thus been proposed to bear specific genetic
      alterations. In order to examine this hypothesis, we have characterized a series
      of 44 flat colorectal neoplasias for their RER status and for somatic APC, KRAS
      and TGF-betaRII genes mutations. Flat colorectal neoplasias were found to be of
      the RER+ subtype in 22% of cases, all of them exhibiting a TGF-betaRII mutation.
      A mutation of the APC and KRAS genes has been found in 42% and 4% of tumors,
      respectively, none of these tumors being of the RER+ subtype. With the exception
      of a low KRAS mutation rate, flat adenomas appear to follow tumorigenesis
      pathways very similar to those identified in exophytic adenomas and carcinomas.

PMID- 9663598
TI  - Radiation dose, chemotherapy and risk of osteosarcoma after solid tumours during
      childhood.
AB  - Osteosarcoma is the most frequent second primary cancer occurring during the
      first 20 years following treatment for a solid cancer in childhood. Using a
      cohort study of children treated for a solid cancer, we investigated the
      incidence and etiology of osteosarcoma as a second malignant neoplasm after
      childhood cancer in a cohort and a case-control study. We analysed the
      relationship between the local dose of radiation and the risk of osteosarcoma,
      taking into account chemotherapy received. A cohort study of 4,400 3-year
      survivors of a first solid cancer during childhood diagnosed in France or the
      United Kingdom, between 1942 and 1986, revealed 32 subsequent osteosarcomas. In a
      nested case-control study, we matched 32 cases and 160 controls for sex, type of
      first cancer, age at first cancer and the duration of follow-up. Parameters
      studied were the incidence of osteosarcoma, the cumulative local dose of
      irradiation and the cumulative dose of chemotherapy received by cases and
      controls. The risk of a osteosarcoma was found to be a linear function of the
      local dose of radiation (excess relative risk per gray=1.8), and was found to
      increase with the number of moles of electrophilic agents per square meter but
      not with other drugs. No interaction was noted between radiotherapy and
      chemotherapy. Bilateral retinoblastoma, Ewing's sarcoma and soft tissue sarcoma
      were found to render patients susceptible to a higher risk of developing an
      osteosarcoma as a second malignant neoplasm. We recommend long-term surveillance
      of patients who were treated during childhood for bilateral retinoblastoma,
      Ewing's sarcoma, soft tissue sarcoma, as well as other first cancer treated with
      radiotherapy plus high doses of chemotherapy, without focusing exclusively on the
      radiation field.

PMID- 9663599
TI  - GM-CSF gene expression and protein production in human colorectal cancer cell
      lines and clinical tumor specimens.
AB  - Granulocyte-macrophage colony stimulating factor (GM-CSF) gene expression and
      protein production were investigated in colorectal cancer cell lines and surgical
      specimens. In 6 of 6 established tumor lines, expression of the GM-CSF gene was
      observed by reverse transcription polymerase chain reaction (RT-PCR).
      Furthermore, for 2 of the lines, the cytokine was detectable in > or = 100 pg/ml
      amounts in culture supernatants by enzyme-linked immunosorbent assay tests.
      Addition of recombinant GM-CSF at doses ranging between 30 pg and 30 ng/ml did
      not appear to affect the proliferation of colorectal cancer cell lines as
      measured by 3H-thymidine incorporation. GM-CSF gene expression was then examined
      in surgical specimens by a densitometry-assisted, semiquantitative RT-PCR
      technique. In the 10 samples analyzed, significantly higher expression was
      detectable in tumors, as compared with autologous healthy mucosa sampled in the
      vicinity (2 cm) or at distance (10 cm) from the neoplastic focus.
      Immunohistochemistry studies performed on 13 specimens led to the identification
      of intracytoplasmic GM-CSF in tumor cells in 9 samples. In 6 of these, positivity
      of stromal fibroblasts and lymphocytes adjacent to the tumor was also observed.
      In contrast, intracellular GM-CSF was only detectable in 2 cases in untransformed
      epithelial cells, close to the neoplasm, but never in healthy mucosa at distance
      from the tumor. Infiltration by dendritic cells (DC) was also investigated. In 5
      of 8 colorectal cancers tested, DC aggregates accounted for more than 10% of
      stromal cells. Lower numbers were detectable in healthy mucosa. However, DC
      infiltration could not be correlated with the presence of GM-CSF-positive
      neoplastic cells in the tumor specimens. Remarkably, cultured DC were unable to
      exert significant cytotoxic activity against colorectal cancer cells in vitro.

PMID- 9663600
TI  - Familial breast cancer in the family-cancer database.
AB  - We use the population-based Family-Cancer Database from Sweden to study familial
      breast cancer. The size of the population and the nation-wide registration of
      cancer offer unique possibilities for epidemiological studies of familial cancer,
      including complete and unbiased identification of cases in the probands and in
      their relatives, and complete and unbiased identification of the family
      relationships. Using the Database, we wanted to answer the following questions:
      (i) proportion of familial breast cancer among all breast cancers; (ii) familial
      relative risks in breast cancer alone or in combination with another cancer,
      defined either through the mother or the daughter; (iii) modification of familial
      risk by age; and (iv) effects of paternal breast cancer alone or in combination
      with maternal breast cancer. The proportion of familial female breast cancer
      among all breast cancers before 54 years of age in Sweden was 8.7%. The familial
      relative risk was about 1.8, but is likely to decrease to about 1.5 in the ageing
      population. The higher familial relative risks were evident in young women, being
      4.0 when both the mothers and their daughters were diagnosed at ages <40 years.
      Paternal breast cancer, in combination with maternal breast cancer, caused a
      large (but not statistically significant) risk in the daughters. In mothers and
      daughters, ovarian but not colon cancer was increased in combination with breast
      cancer.

PMID- 9663601
TI  - Second cancers following in situ carcinoma of the breast.
AB  - Carcinoma in situ (CIS) of the breast has increased many-fold in incidence rates
      and as a proportion of new breast cancers following the introduction of
      mammographic breast screening. To provide population-based estimates of invasive
      breast cancer risk following CIS, we linked data on 249 incident primary CIS
      (median age 53 years) to the Cancer Registry of the Swiss Canton of Vaud (about
      600,000 inhabitants) over the period 1977-1994. Women with concurrent invasive
      cancers of the breast were not included. Standardized incidence ratios (SIR) were
      determined according to the exact Poisson distribution, with stratification for
      age and year of diagnosis. A total of 24 cases of breast cancer vs. 3.4 expected
      [SIR = 7.2, 95% confidence interval (CI): 4.6-10.6], and 7 cases of other
      neoplasms (except non-melanomatous skin cancer) vs. 6.9 expected (SIR=1.0, 95%
      CI: 0.4-2.1) were observed. The SIR was 10.4 during the first year, 5.6 between I
      and 4 years, and 7.7 after > or = 5 years after CIS diagnosis. SIRs were
      consistent in women below and above age 55 years, but somewhat higher for ductal
      (SIR=8.6) than lobular (SIR = 4.2) CIS. Six deaths from breast cancer were
      observed vs. 1.5 expected (standardized mortality ratio=4.0, 95% CI: 1.5-8.7). In
      13/19 ductal CIS, but in 2/4 lobular CIS, invasive cancer occurred in the same
      breast. In most women, CIS and subsequent invasive cancer showed the same
      morphological (i.e., ductal or lobular) features. The cumulative risk of breast
      cancer was 16% 10 years after CIS diagnosis, emphasizing the importance of
      adequate surveillance of women after CIS of the breast.

PMID- 9663602
TI  - Inhibition of tumor growth in vivo by hyaluronan oligomers.
AB  - One of the critical events in tumor growth and metastasis is the interaction
      between tumor cells and host tissue stroma, mediated by different adhesion
      receptor repertoires in different tumor cell types. Several lines of evidence
      indicate that interaction between the hyaluronan receptor CD44, expressed on
      tumor cells, and host tissue stromal hyaluronan can enhance growth and
      invasiveness of certain tumors. Disruption of CD44-hyaluronan interaction by
      soluble recombinant CD44 has been shown to inhibit tumor formation by lymphoma
      and melanoma cells transfected with CD44. Since hyaluronan is a ubiquitous
      glycosaminoglycan polymer from which oligosaccharides of defined size can be
      readily purified, we tested the ability of hyaluronan oligomers to inhibit tumor
      formation by subcutaneously (s.c.) injected B16F10 melanoma cells. Our results
      indicate that hyaluronan oligomers injected at concentrations as low as 1 mg/ml
      can markedly inhibit B16F10 melanoma growth, providing a potentially attractive
      reagent for the control of local tumor development.

PMID- 9663603
TI  - Dissemination capacity of murine lymphoma cells is not dependent on efficient
      homing.
AB  - The extravasation of normal lymphocytes from blood into tissues is controlled by
      adhesion molecules ("homing receptors") that mediate their interaction with
      endothelial cells. It is an intriguing question whether malignant cells use the
      same pathways for hematogenous dissemination and whether these molecules are
      involved in the organ-specific formation of metastasis. To analyze the migration
      behavior of lymphoma cells in vivo, we here used several lines and sublines which
      exhibit differential expression of the lymph node homing receptor L-selectin and
      the mucosa-specific integrin alpha4beta7. We demonstrate that the ability of the
      various types of cells tested to accumulate in lymph nodes within the first 24 hr
      after intravenous (i.v.) injection is negligible, independent of their homing
      receptor expression profile. Our data indicate that lymphoma cells have, in
      comparison with naive lymphocytes, an impaired capacity to extravasate via high
      endothelial venules (HEV). Instead they predominantly accumulate in lung and
      liver, similar to activated lymphocyte populations. Nevertheless, most of the
      lymphoma lines tested readily form lymph node metastases in vivo. In addition,
      blockade of L-selectin by continual treatment with an anti-L-selectin antibody
      did not prevent metastatic growth of TK-1 cells in peripheral lymph nodes. We
      conclude that the expression of homing receptors and a high extravasation
      efficiency of neoplastic cells is not a prerequisite for their dissemination into
      lymphatic tissue.

PMID- 9663604
TI  - Cellular kinetic differences between Hodgkin's and anaplastic large cell
      lymphomas: relation to the expression of p34cdc2 and cyclin B-1.
AB  - Our study was designed to compare cellular kinetic parameters of classical
      Hodgkin's disease (HD) with those of anaplastic large cell lymphomas (ALCL-C,
      common type; and ALCL-HL, Hodgkin's like), with a particular focus on the G2/M
      transition. These disorders share some phenotypic properties, e.g., CD30
      positivity of putative neoplastic cells. The percentages of cells expressing
      p34cdc2 (p34) and cyclin B-1 (cyclin-B), which form a complex (maturation/mitosis
      promoting factor, MPF) regulating the G2-M phases of the cell cycle, were also
      registered. Highly significant differences between HD and ALCL-C were recognized:
      a) in HD, evidence for abortive mitosis (i.e., difficulty to proceed beyond the
      metaphase stage) and consequent multinucleation and/or deletion of CD30+ cells
      was prominent, in contrast to ALCL-C. This was associated with a markedly lower
      fraction of large atypical cells (LAC) expressing cyclin-B in the cytoplasm and
      the nucleus (C + N) in HD than in ALCL-C; b) the extent of multinucleation of
      CD30+ cells in HD, but not in ALCL-C, was correlated with the %p34+ LAC; c) the
      proportions of LAC expressing p34 and/or cyclin-B (C) were positively related to
      the percentages of cyclin-B (C + N)+ LAC in ALCL-C but not in HD; d) in HD, in
      contrast to ALCL-C, the size of the fraction of cyclin-B (C + N)+ LAC did not
      correlate with the ana/telophase indices (ATI, reflecting successful completion
      of mitosis) and the magnitude of cell loss; e) in ALCL-C, the percentages of p34+
      LAC were positively correlated with ATI or the degree of CD30+ cell deletion, but
      inversely in HD. With regard to all parameters mentioned above, ALCL-HL tended to
      take an intermediate position between HD and ALCL-C, but sided more with the
      latter. In conclusion, our present results suggest a derangement of MPF kinetics
      and functions that is more profound in HD than in ALCL-C.

PMID- 9663605
TI  - Differential characteristics of two new tumorigenic cell lines of human breast
      carcinoma origin.
AB  - Permanent human tumor cell lines are an important tool for the study of breast
      cancer. Two new breast cancer cell lines (BrCa-MZ-01 and BrCa-MZ-02) were
      isolated from a solid tumor and a pleural effusion, respectively. One cell line
      was established from a medullary carcinoma, the other from a ductal carcinoma.
      These cells exhibit ultrastructural and immunohistochemical features of
      epithelial cells of mammary origin. Intermediate filament and cytokeratin typing
      showed a clear predominance of the simple-epithelial cytokeratins CK 8, CK 18 and
      CK 19, although the expression was reduced in comparison to the hormone receptor
      positive reference cell lines MCF-7 and ZR-75-1. Both cell lines produced slow
      growing tumors after subcutaneous (s.c.) transplantation of 1 x 10(7) viable
      tumor cells into nude mice. The cell line BrCa-MZ-01 expresses the estrogen and
      progesterone receptor, whereas the cell line BrCa-MZ-02 remains negative. Both
      cell lines are positive for secretion of platelet-derived growth factor (PDGF)
      and transforming growth factor-beta (TGF-beta), whereas interleukin-6 (IL-6) is
      only secreted by the cell line BrCa-MZ-02.

PMID- 9663606
TI  - Characterization of a newly established endometrial stromal sarcoma cell line.
AB  - We describe a newly established human sarcoma cell line derived from an
      endometrial stromal sarcoma (ESS). The cell line has been maintained in long-term
      cell culture for more than 2 years. It has been repeatedly analyzed in terms of
      morphology, immunocytochemical features, ultrastructure and karyotypic
      characteristics. In contrast to uniform endometrial stromal differentiation in
      vivo, the tumor cells were shown to display distinct phenotypical heterogeneity
      in vitro. In addition to the predominant cell type, which retained sarcomatous
      differentiation, foci of epithelial-like cells were observed in the cell culture.
      Immunocytochemical and ultrastructural analysis demonstrated a mainly mesenchymal
      phenotype with signs of epithelial characteristics, such as expression of
      cytokeratins, and the presence of desmosomes and kinetocilia, respectively.
      Cytogenetic analyses in early and late passages revealed unbalanced
      translocations between chromosomes 3 and 6 and an additional i(19)(q10), as
      common karyotypic changes in all tumor cells, indicating a monoclonal origin. Our
      new cell line can be used as an in vitro model to study the mechanisms of
      heterogeneous differentiation patterns in ESS.

PMID- 9663607
TI  - SV40 Tag transformation of the normal invasive trophoblast results in a
      premalignant phenotype. I. Mechanisms responsible for hyperinvasiveness and
      resistance to anti-invasive action of TGFbeta.
AB  - Invasion of the uterus by first trimester human placental extravillous
      trophoblast (EVT) cells depends on mechanisms shared by malignant cells. However,
      unlike tumor invasion, trophoblast invasion of the uterus is stringently
      controlled in situ by local molecules such as transforming growth factor
      (TGF)beta. Since EVT cells possess active invasion-associated genes but are
      nontumorigenic, our objective was to induce premalignant and then malignant
      phenotype into a normal EVT cell line in order to identify the molecular basis of
      tumor progression. Simian virus 40 large T antigen (SV40 Tag) was introduced into
      a normal human first trimester invasive EVT cell line, HTR8, established in our
      laboratory. Since the HTR8 line has a limited in vitro lifespan of 12-15
      passages, SV40 Tag-transformed cells were selected on the basis of extended
      lifespan. A long-lived line, RSVT-2, was produced and an immortalized subclone,
      RSVT2/C, was further derived under a forced crisis regimen. We examined
      transformation-induced alterations in proliferative and invasive abilities,
      responses to the invasion and proliferation-regulating growth factor TGFbeta and
      changes in gene expression for invasion-associated enzymes or enzyme inhibitors.
      RSVT-2 and RSVT2/C cell lines were hyperproliferative and hyperinvasive when
      compared with the parental HTR8 cell line. They were also variably resistant to
      the anti-proliferative and anti-invasive signals from TGFbeta. Since both cell
      lines remained non-tumorigenic in nude mice, these properties indicate that they
      attained a premalignant phenotype. Both cell lines showed reduced expression of
      tissue inhibitor of metalloproteases (TIMP)-1, while TIMP-2 and plasminogen
      activator inhibitor (PAI)-I expression was was also reduced in RSVT2/C cells,
      thus contributing to their hyperinvasiveness. Their resistance to the anti
      invasive action of TGFbeta was explained by the failure of TGFbeta to upregulate
      TIMPs and PAI-I, in contrast to the TGFbeta-induced upregulation noted in
      parental HTR8 cells.

PMID- 9663608
TI  - SV40 Tag transformation of the normal invasive trophoblast results in a
      premalignant phenotype. II. Changes in gap junctional intercellular
      communication.
AB  - Poor gap junctional intercellular communication (GJIC) has been associated with
      uncontrolled cell growth and neoplasia. We have successfully propagated normal
      first trimester invasive extravillous trophoblast (EVT) cells, and have produced
      premalignant EVT lines after SV40 Tag transformation: RSVT-2 is an uncloned line
      that is long-lived; RSVT2/C is a clonal line that is immortal. Both are
      hyperproliferative, hyperinvasive and variably refractory to the anti
      proliferative and anti-invasive effects of transforming growth factor beta
      (TGFbeta). Possible changes in gap junctions during the transition of normal
      invasive EVT cells to the premalignant stage were examined by comparing
      expression of connexin proteins (by immunolabeling for Cx26, Cx32, Cx40, Cx43),
      and mRNA (by Northern blot with cDNA probes for Cx26, Cx32, Cx43), and functional
      GJIC (by dye transfer using the preloading method) in normal parental EVT cells
      and their SV40 Tag transformants. Results from immunofluorescence and Northern
      blot analysis revealed that, of the panel of connexins examined, only Cx43 was
      variably expressed in these cell lines in vitro. Expression of Cx43 protein and
      mRNA was abundant in normal EVT cell line HTR8, reduced in long-lived RSVT-2
      cells and undetectable in immortalized RSVT2/C cells. GJIC, as measured by dye
      transfer between donor and recipient cells, was also similarly reduced in
      recipient RSVT-2 cells, and drastically reduced in RSVT2/C cells, irrespective of
      whether the dye donor was of the same cell type (homocellular coupling) or HTR8
      cells (heterocellular coupling). Treatment with TGFbeta reduced Cx43 mRNA
      expression as well as GJIC in normal EVT cells, but not in the SV40 Tag
      transformants. Our findings suggest that downregulation of connexins with the
      resultant impairment in GJIC is an early event in tumor progression, as observed
      in the premalignant SV40 Tag transformants.

PMID- 9663609
TI  - Human neuroblastoma cells produce extracellular matrix-degrading enzymes, induce
      endothelial cell proliferation and are angiogenic in vivo.
AB  - Direct experimental evidence shows that tumor growth and metastases are
      angiogenesis-dependent. Neuroblastoma (NB) is the most common extracranial
      malignant solid tumor of childhood. In this study, we investigated 2 human NB
      cell lines, LAN-5 and GI-LI-N, for their capacity to secrete 2 extracellular
      matrix-degrading enzymes, MMP-2 and MMP-9, and to induce in vitro human
      microvascular endothelial cells (EC) to proliferate and in vivo angiogenesis in
      the chick embryo chorio-allantoic membrane (CAM) assay. Conditioned medium (CM)
      from both cell lines stimulated in vitro EC proliferation and the effect of LAN-5
      CM was higher than that of GI-LI-N cells. Moreover, anti-VEGF, but not anti-FGF2
      antibodies, prevented growth increment of EC. NB cell lines secreted the active
      form of MMP-2 almost exclusively, LAN-5 cells more than GI-LI-N cells. Both cell
      lines, LAN-5 cells more than GI-LI-N ones, induced angiogenesis in the CAM assay.
      Our data suggest that the 2 NB cell lines are angiogenic, to LAN-5 cells more
      than GI-LI-N ones. LAN-5 cells are indeed endowed with a more aggressive and
      invasive phenotype.

PMID- 9663610
TI  - Angiogenic potential of malignant and non-malignant human breast tissues in an in
      vivo angiogenesis model.
AB  - Tumors need to acquire an angiogenic phenotype for outgrowth and metastasis
      formation. Limited information on the angiogenic potential of specific tissues,
      especially human breast tissues is available. Here we describe an in vivo model,
      using the dorsal skin fold chamber in immunodeficient nude mice, where various
      tissues of human breast origin were xenografted and evaluated for their
      angiogenesis-inducing potential. We found that angiogenesis was abundantly
      induced by all breast carcinoma tissue samples. Similar angiogenesis was induced
      by tissue samples from breasts with hyperplasia and apocrine metaplasia.
      Histologically normal tissues adjacent to the tumor induced angiogenesis in 66%
      of the cases. Angiogenesis was not induced by control tissues from normal healthy
      breasts, obtained after cosmetic breast reduction. Angiogenesis induction
      parallelled VEGF production by the tumor cells. The tissue induced
      neovascularization, found both around and in the human tissue, was functional
      since a tail vein injection of albumin-FITC revealed positive tumor
      microcirculation within 5 min, while the tumor tissue still consisted of vital
      human epithelial cells after 14 days.

PMID- 9663611
TI  - Increased IL-12 P40 homodimer secretion by spleen cells during in vivo growth of
      the BW-19 T cell hybridoma accompanies suppression of natural immunity.
AB  - The high capacity of the T cell hybridoma BW-19 to metastasize to the spleen,
      despite its high and moderate sensitivity to lysis by macrophages and natural
      killer (NK) cells, respectively, appears to be linked to its capacity to suppress
      local resident NK cell and macrophage activity. Such suppression of splenic NK
      cell and macrophage activity is accompanied by an increased production of the p40
      subunit of interleukin-12 (IL-12) by spleen cells. Closer examination revealed
      that most of the p40 subunit is present under the form of the homodimer (p40)2,
      whereas the heterodimeric form of IL-12 is present only in small amounts. Since
      (p40)2 is known to be a strong antagonist of IL-12-mediated effects, i.e., NK
      cell activation and interferon-gamma (IFN-gamma) secretion, the increased
      production of (p40)2 after BW-19 cell inoculation may contribute to the
      suppression of NK cell and macrophage activity. In addition, we found that the
      high production of (p40)2 in our tumor model was accompanied by a drastic
      decrease in IL-2 and IFN-gamma production by spleen cells, further favoring the
      possibility that (p40)2 plays a role in the suppression of NK cell and macrophage
      cytotoxicity. Our results show that normal spleen cells can produce (p40)2 in
      response to cancer cell growth in vivo and are highly suggestive of a role for
      (p40)2 in the suppression of natural immunity.

PMID- 9663612
TI  - Alpha1-adrenoceptor stimulation enhances experimental gastric carcinogenesis
      induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.
AB  - The effect of prolonged administration of the norepinephrine-mimicking agent
      metaraminol, the alpha1-adrenergic agonist phenylephrine and the alpha2
      adrenergic agonist clonidine on the incidence of gastric cancers induced by N
      methyl-N'-nitro-N-nitrosoguanidine (MNNG), the ornithine decarboxylase activity
      of the gastric cancer and the labeling index of the gastric mucosa were
      investigated in Wistar rats. Rats received s.c. injections of metaraminol,
      phenylephrine or clonidine every other day after 20 weeks of oral treatment with
      MNNG. At week 52, administration of metaraminol and phenylephrine at the higher
      dose significantly increased the incidence of gastric cancers, the ornithine
      decarboxylase activity of the gastric cancers and the labeling index of the
      antral epithelial cells. Administration of phenylephrine at the lower dose and
      clonidine at both doses had no significant effect on the incidence of gastric
      cancers, the ornithine decarboxylase activity of the gastric cancers or the
      labeling index of the gastric mucosa. Our results suggest that adrenoreceptor
      stimulation enhances gastric carcinogenesis and that such enhancement is mediated
      through alpha1-adrenoceptors without alpha2-adrenoceptor involvement.

PMID- 9663613
TI  - Induction of anti-tumour immunity by suicide-gene-modified HPV-16-transformed
      hamster cells.
AB  - From K3/II, which is a highly oncogenic HPV16-transformed Syrian hamster cell
      line, thymidine-kinase(TK)-less cells, denoted B 49, were derived. B49 cells were
      transfected by a plasmid containing the herpes-simplex-virus TK gene (HSV TK) and
      several sub-lines expressing this gene were isolated from the transfected
      cultures. The HSV TK+ cells were highly sensitive to ganciclovir (GCV) and other
      anti-viral substances whose inhibitory effect is based on their phosphorylation
      by HSV TK. One of the cell lines, denoted KL1/6, exhibited relatively high
      stability of the HSV TK+ phenotype and was used in subsequent experiments. When
      KL1/6 cells were co-cultivated in the presence of GCV with various other cell
      lines of hamster, mouse or monkey origin, the by-stander effect (BE) was
      observed. GCV treatment of hamsters prevented development of tumours after the
      administration of KL1/6 cells but not K3/II cells. The treatment of animals with
      already established KL1/6-induced tumours resulted in tumour regression in all
      instances, but complete regression was observed only in animals carrying small
      tumours. The BE of KL1/6 cells on K3/II cells was also seen in vivo. In addition,
      concomitant immunity was observed in animals simultaneously inoculated with KL1/6
      cells and K3/11 cells at 2 separate sites of the body. This effect was evident
      not only in animals in which KL1/6 tumours developed, but also in those in which
      tumour outgrowth was prevented by GCV treatment. In other experiments it was
      demonstrated that one KL1/6 + GCV treatment resulted in partial resistance, 2
      such treatments in complete resistance to the challenge with K3/II cells.

PMID- 9663614
TI  - In vivo eradication of an established human melanoma by an in vitro generated
      autologous cytotoxic T cell clone: a SCID mouse model.
AB  - Tumor-specific T cells may be induced in vitro and in vivo. A tumor, however, is
      able to avoid recognition by T cells by various mechanisms, and it has therefore
      been difficult to use these cells for the treatment of cancer. To investigate
      these mechanisms, it would be desirable to identify a suitable in vivo model
      system to avoid the ethical considerations that are obviously limiting factors
      for studies in humans. In addition, tumor antigens, although recognized, may not
      always function as rejection antigens, thus, the establishment of an in vivo
      model is crucial for preclinical studies to allow the characterization of
      effective rejection antigens. We show here that the immunodeficient scid mouse is
      an excellent model system. Using this system, we demonstrate that an already
      established human melanoma tumor is eradicated by an in vitro generated
      autologous cytotoxic T cell clone.

PMID- 9663615
TI  - High incidence of thyroid cancer in central Italy.

PMID- 9663616
TI  - Use of sterile syringes and aseptic drug preparation are important components of
      HIV prevention among injection drug users.

PMID- 9663617
TI  - The importance of preventing hepatitis C virus infection among injection drug
      users in the United States.
AB  - Injection drug use is the single most important risk factor for acquiring
      hepatitis C virus (HCV) infection. Injection drug users acquire this infection
      rapidly after initiating injection practices, and up to 90% of them are
      chronically infected with HCV. HCV infection is a major cause of chronic liver
      disease, and persons infected with HCV are at risk for chronic hepatitis,
      cirrhosis, and primary hepatocellular carcinoma, and they risk transmitting HCV
      infection to others. Preventive measures for HCV infection are limited. The
      heterogeneous nature of HCV and its ability to undergo rapid mutation appear to
      prevent the development of an effective neutralizing immune response, obstructing
      development of a vaccine. Prevention of HCV infection must rely on educational
      and programmatic efforts aimed at preventing drug use, providing substance abuse
      treatment for persons who inject illicit drugs, and encouraging safer injection
      practices. These efforts should include messages about the risk and prevention of
      all blood-borne pathogens, including HCV, hepatitis B virus, and human
      immunodeficiency virus.

PMID- 9663618
TI  - Prevalence and incidence of hepatitis C virus infection among young adult
      injection drug users.
AB  - Through community-based outreach, young adult injection drug users (IDUs) were
      enrolled in a prospective study of the prevalence, incidence, and risk factors
      for hepatitis C virus (HCV) infection. Demographics and information on sexual and
      injecting practices were collected during semiannual interviews, and HCV
      infection was evaluated using a second-generation antibody assay. Of the 229
      participants, 86 (37.6%) were HCV-seropositive at baseline. After adjusting for
      injecting frequency and duration by logistic regression, HCV seroprevalence was
      independently associated with reusing syringes at least once in the past 6 months
      (odds ratio [OR]=3.81, 95% confidence interval [CI] 1.39-11.00), injecting the
      first time with someone > or =5 years older (OR=2.99; 95% CI, 1.43-6.23) or alone
      (OR=4.02; 95% CI, 1.12-14.43) versus with someone <5 years older, and injecting
      cocaine or speedball exclusively (OR=4.29; 95% CI, 1.53-12.01) or with other
      drugs (OR=5.27; 95% CI, 2.62-10.64) versus injecting no cocaine in the past 6
      months. Of the 105 originally HCV-seronegative participants who returned for
      follow-up, 13 seroconverted (incidence rate=16.0/100 person-years). On bivariate
      analysis, HCV seroconversion was significantly associated with injecting for <2
      years (relative risk [RR]=7.3; 95% CI, 1.6-32.8) and continuing to inject during
      follow-up (RR=4.4; 95% CI, 1.0-19.9). Young adult IDUs are at high risk for HCV
      infection. These data support the need for wider legal access to sterile
      syringes, as well as expanded community outreach education to this population to
      prevent transmission of HCV.

PMID- 9663619
TI  - Infection control basis for recommending one-time use of sterile syringes and
      aseptic procedures for injection drug users.
AB  - Persons who inject drugs are at increased risk for many infectious diseases,
      including HIV. Reuse of syringes and needles and other equipment used to prepare
      and inject drugs increases the risk of infection with blood-borne and other
      pathogens. According to standard infection control guidelines, needles and
      syringes and their contents fall within the critical category of patient contact
      because they enter the normally sterile vascular space. Medical equipment
      considered critical should be treated or prepared in a manner that destroys
      vegetative and spore-forming microbes. The simplest way to ensure this level of
      hygienic practice is to use prepackaged, sterile, disposable needles and syringes
      and to use sterile drug preparation equipment and drugs. These recommendations
      are made as part of a comprehensive infection prevention program designed for
      injection drug users.

PMID- 9663620
TI  - Parenteral transmission of HIV among injection drug users: assessing the
      frequency of multiperson use of needles, syringes, cookers, cotton, and water.
AB  - OBJECTIVES: To describe and estimate the frequency of different types of drug
      preparation and injection practices that could result in the transfer of blood
      and blood-borne infections among injection drug users (IDUs). METHODS: We
      analyzed data from interviews administered to 12,323 active IDUs recruited from
      19 sites in the United States. The interviews ascertained drug-related behaviors
      during the previous 30 days. RESULTS: 31.9% of IDUs reported that they engaged in
      the use of both needle/syringes and cookers/cotton/water previously used by
      another IDU; 8.6% engaged only in the use of needle/syringes previously used by
      another IDU; 17.5% engaged only in the use of cookers/cotton/water previously
      used by another IDU; and 42.0% reported using neither needle/syringes nor
      cookers/cotton/water previously used by another IDU. Only 12.6% reported use of
      new (never-used) needle/syringes. The 3935 IDUs who used both needle/syringes and
      cookers/cotton/water that had been previously used by another IDU had more than
      311.000 potential exposures to blood-borne infections from these high-risk
      practices in 30 days; about 64% of these exposures were from multiperson use of
      cookers/cotton/water. CONCLUSIONS: Programs to limit parenteral transmission of
      HIV and other blood-borne infections among IDUs must consider all drug
      preparation and injection practices that could allow transfer of blood and blood
      borne infections among IDUs.

PMID- 9663621
TI  - Feasibility of one-time use of sterile syringes: a study of active injection drug
      users in seven United States metropolitan areas.
AB  - OBJECTIVES: To assess the feasibility of advice to injection drug users (IDUs) to
      use a sterile syringe for each injection, we examined sources of syringes,
      syringe use and reuse, and barriers to and facilitators of compliance with the
      one-time use of syringes by active IDUs in seven U.S. metropolitan areas.
      METHODS: Brief, interviewer-administered surveys were completed by 593 active
      IDUs, defined as injection reported within the past 90 days, in seven U.S.
      metropolitan areas characterized by various restrictions on syringe acquisition
      and possession. RESULTS: Most of the IDUs interviewed were male (69%) and African
      American (74%). Overall, only 23% obtained the most recently used syringe from a
      reliable source of sterile syringes (i.e., pharmacy or syringe exchange program
      [SEP]). The median number of injections per most recently used syringe was 3
      (mean=5.2); 21% used the syringe only once. IDUs were more likely to have used a
      reliable source for obtaining their most recent syringe in cities with a SEP
      (odds ratio [OR]=5.3; 95% confidence interval [CI] 3.3-8.5) or without
      restrictive paraphernalia laws (OR=0.1; 95% CI 0.1-0.3). To facilitate one-time
      use of sterile syringes, IDUs recommended the provision of free syringes (50.3%),
      access to a SEP (38.1%), and access to pharmacy purchase of syringes (24.0%).
      CONCLUSIONS: Restrictions on syringe availability and the beliefs and practices
      of IDUs are barriers to the public health recommendation of one-time use of
      sterile syringes for IDUs who cannot stop injecting. Increased access to legal,
      inexpensive sterile syringes and education about the merits of one-time use are
      needed.

PMID- 9663622
TI  - Syringe use and reuse: effects of syringe exchange programs in four cities.
AB  - We determined the effect of syringe exchange programs (SEPs) on syringe reuse
      patterns. Five methods were employed to estimate injections per syringe made by
      exchange clients in four cities. In San Francisco, Chicago, and Baltimore, self
      reported data on the number of injections per syringe were obtained. In New
      Haven, self-reported injection frequencies were combined with syringe tracking
      data to derive two methods for estimating the mean injections per syringe. The
      average number of injections per syringe declined by at least half after
      establishment of SEPs in New Haven, Baltimore, and Chicago, all cities where such
      an analysis could be made. There were significant increases in the percentages of
      exchangers reporting once-only use of their syringes in San Francisco, Baltimore,
      and Chicago, all cities where the data were amenable to this form of analysis.
      Self-report and syringe tracking estimates were in agreement that SEP
      participation was associated with decreases in syringe reuse by drug injectors.
      SEP participation was associated with increases in the once-only use of syringes.
      These findings add to earlier studies supporting the role of SEPs in reducing the
      transmission of syringe-borne infections such as HIV and hepatitis.

PMID- 9663623
TI  - A sterile syringe for every drug user injection: how many injections take place
      annually, and how might pharmacists contribute to syringe distribution?
AB  - Our objectives were to estimate the annual number of injections by injection drug
      users (IDUs) in the United States of America, and to describe the potential role
      of pharmacists in providing IDUs with a sterile syringe for every injection. We
      estimated the number of annual injections by IDUs for the United States, selected
      U.S. states, and selected U.S. cities according to the following formula: number
      of injections per year = (number of IDUs) x (average number of injections per IDU
      per day) x 365. Data were obtained from published articles, personal
      communications with local experts, and selected national databases. We also
      reviewed published and unpublished studies of pharmacy kits, pharmacist
      attitudes, and pharmacist practices in the United States and abroad. Between 920
      million and 1.7 billion injections by IDUs take place each year in the United
      States. We estimated 12 million injections per year in San Francisco and >80
      million in New York City. A similar number of syringes would be needed to satisfy
      the goal of a sterile syringe for every injection. Pharmacy-based strategies,
      including the sale of kits for injection drug use, have provided sterile syringes
      to IDUs in Europe, Australia, and New Zealand. Modification of laws restricting
      syringe purchase and possession has led to marked increases in purchase of
      syringes from pharmacies and reductions in needle-sharing. In conclusion, large
      numbers of syringes would be required to provide a sterile syringe for every
      injection, but significant numbers of pharmacists seem to be willing to play a
      central role in syringe sale and distribution. Outreach programs should emphasize
      that using a sterile syringe for every injection is the optimal HIV prevention
      practice for IDUs who cannot or will not stop injecting. Pharmacy-based syringe
      sale or distribution has the potential to augment current efforts to prevent HIV
      infection in IDUs, their sex partners, and their children.

PMID- 9663624
TI  - "Single-use" needles and syringes for the prevention of HIV infection among
      injection drug users.
AB  - Providing single-use injection equipment to persons who inject illicit drugs
      would appear to be an effective method for reducing HIV transmission. However,
      interviews with manufacturers, syringe exchange program staff, and drug users
      revealed numerous difficulties with such a technologic solution. All designs for
      such equipment can be defeated and should probably be called difficult-to-reuse
      equipment. There are problems with consumer acceptance of difficult-to-reuse
      equipment and with safe disposal of large amounts of biohazardous waste. Despite
      these problems, it would be useful to conduct additional research, particularly
      on the potential for placing difficult-to-reuse equipment into shooting
      galleries.

PMID- 9663625
TI  - Enough sterile syringes to prevent HIV transmission among injection drug users in
      Montreal?
AB  - The HIV epidemic among injection drugs users in Montreal continues unabated. We
      wished to know whether sufficient syringes were being distributed to provide for
      the needs of injection drug users (IDUs) in Montreal. Using data from several
      sources, including the estimated number of active IDUs in 1994 and the injection
      frequency according to the drug consumed, we calculated the number of syringes
      required by IDUs. The number of syringes estimated was compared with the number
      of syringes distributed by needle exchange programs or sold in private
      pharmacies. Overall, we estimated that in 1994 about 10,683,000 syringes were
      required by the 10,000 IDUs in Montreal. Because about 338,000 syringes were
      distributed, <5% of the need was being met. The parameters in our analysis,
      particularly the number of IDUs in Montreal, drug use, and the frequency of
      injection, are subject to uncertainty. Nevertheless, because of the disparity
      between the small proportion of syringes distributed and the number required, it
      is unlikely that sufficient syringes are available to ensure access to clean
      needles and prevent HIV transmission. Measures should be taken to expand syringe
      distribution to Montreal IDUs.

PMID- 9663626
TI  - The legal environment impeding access to sterile syringes and needles: the
      conflict between law enforcement and public health.
AB  - This article examines the legal environment for programs to prevent transmission
      of HIV and other blood-borne diseases among injection drug users (IDUs). Cost
      effective public health programs often have questionable legal authority, and
      health professionals, community activists, and IDUs may be subject to arrest and
      prosecution. Legal impediments to the sale and distribution of syringes exist in
      every state: 47 states have drug paraphernalia statutes, 8 states have syringe
      prescription statutes, and 23 states have pharmacy regulations or practice
      guidelines. The Mail Order Drug Paraphernalia Act permits federal enforcement
      against individuals who knowingly sell or distribute syringes to IDUs. Congress
      has prohibited the use of federal funds for syringe exchange programs (SEPs).
      Legal restrictions on access to sterile syringes present formidable obstacles to
      public health prevention. These restrictions render it much more difficult for
      pharmacists to sell syringes over the counter or for physicians to prescribe
      syringes, create a chilling effect on IDUs seeking to comply with medical advice
      and protect themselves and their partners from disease, and place significant
      obstacles on the lawful establishment and operation of SEPs. Public health
      authorities have only sometimes creatively circumvented legal restrictions
      through judicial declarations of lawfulness, municipal declarations of a "state
      of emergency," and by use of the "necessity" defense. I recommend repeal of
      syringe prescription statutes and reform of drug paraphernalia statutes and
      pharmacy regulations.

PMID- 9663627
TI  - Arrests and incarceration of injection drug users for syringe possession in
      Massachusetts: implications for HIV prevention.
AB  - Multiperson use of syringes is a major risk behavior responsible for the spread
      of HIV-1 among injection drug users (IDUs). In Massachusetts, two laws regulate
      syringes: one is a prescription law prohibiting possession or purchase of
      syringes without a prescription, and the other makes it illegal to possess drug
      paraphernalia, including syringes. In 1993, Massachusetts amended the
      prescription law to permit the establishment of syringe exchange programs in two
      cities. Enrolled participants are allowed to possess syringes anywhere in the
      state, and about 5% of the estimated 40,000 IDUs in Massachusetts are program
      participants. To understand how HIV prevention efforts with active IDUs may be
      constrained by the enforcement of laws criminalizing possession of syringes after
      the amendment in the law, we reviewed data from multiple sources to assess the
      number of arrests for syringe possession in 10 large cities in Massachusetts to
      evaluate incarceration rates and lengths of sentences for those convicted of
      syringe possession and to estimate costs of incarceration for those convicted of
      syringe possession. At least 824 persons were arrested for syringe possession in
      1995. In examining the data on convictions, we found that 417 persons were
      convicted in 1994 of syringe possession in the absence of other serious charges,
      and of these, 41.0% were sentenced to incarceration. The average sentence imposed
      was 5 months (range, 3 days-2 years). Assuming that those convicted serve about
      two thirds of their sentences, the cost of incarceration was estimated at
      $1,140,183 excluding costs for arrest, pretrial detention, prosecution, or other
      costs of enforcement. Costs for incarcerating persons convicted of both syringe
      and drug possession were not included; the total cost of incarceration of persons
      convicted of possession of a syringe, with or without other major charges, is
      probably considerably higher. Had these funds been allocated to pay for drug
      treatment, 1629 admissions to drug detoxification programs could have been
      purchased. Retaining drug paraphernalia and syringe prescription laws in
      Massachusetts may contribute to HIV transmission. These findings support the
      recommendation of the American Medical Association to modify drug paraphernalia
      laws so that IDUs can purchase and possess syringes without a prescription.

PMID- 9663628
TI  - Injection and syringe sharing among HIV-infected injection drug users:
      implications for prevention of HIV transmission. Supplement to HIV/AIDS
      Surveillance Group.
AB  - Because HIV-infected injection drug users (IDUs) can transmit HIV infection, we
      investigated factors associated with sharing of syringes in the past year among
      IDUs infected with HIV. We analyzed data from an interview survey of 11,757
      persons > or = 18 years of age with HIV or AIDS between June 1990 and August 1995
      who were reported to 12 state or city health departments in the United States. Of
      the 1527 persons who had ever shared syringes and reported injecting in the 5
      years before the interview, 786 (51%) had injected in the year before interview,
      and of these, 391 (50%) had shared during that year. IDUs who were aware of their
      HIV infection for >1 year were less likely to share (43%) than those who were
      aware of their infection for 1 year or less (65%, adjusted odds ratio=2.15, 95%
      confidence interval, 1.52-3.03). The only statistically significant time trend
      was that the proportion of IDUs from Connecticut who shared decreased from 71% in
      1992 to 29% in 1995. This trend appears to be related to the 1992 changes in
      Connecticut laws that allowed purchase and possession of syringes without a
      prescription. Because many HIV-infected IDUs continue to inject and share,
      prevention efforts should be aimed at HIV-infected IDUs to prevent transmission
      of HIV. Early HIV diagnosis and access to sterile syringes may be important
      methods for reducing syringe sharing by HIV-infected IDUs.

PMID- 9663629
TI  - Community support for needle exchange programs and pharmacy sale of syringes: a
      household survey in Baltimore, Maryland.
AB  - In October 1995, community attitudes toward needle exchange programs were
      assessed in Baltimore, Maryland. Household interviews were conducted with a
      random sample of residents living within six contiguous census tracts.
      Multivariate logistic regression was used to determine which factors were
      independently associated with acceptance of needle exchange programs. Of 274
      eligible respondents contacted, 138 (50%) completed the interview. Respondents
      were statistically similar to the 1990 census population by income but were more
      likely to be female, black, between the ages of 35 and 44 years, and to have
      attended college or be a college graduate. Although 72% of respondents thought
      needle exchange programs would attract injection drug users to the neighborhood,
      65% favored needle exchange, and 47% favored selling needles in a pharmacy
      without a prescription. Factors independently associated with acceptance of
      needle exchange programs included the perceptions that needle exchange programs
      decrease the number of discarded needles on the street, that needle exchange
      programs do not encourage a person's injection drug use, and that needle exchange
      programs decrease HIV incidence. Despite concern about attracting injection drug
      users to the neighborhood, support for needle exchange programs was high.

PMID- 9663630
TI  - Pharmacists' attitudes about pharmacy sale of needles/syringes and needle
      exchange programs in a city without needle/syringe prescription laws.
AB  - We assessed pharmacists' practices for needle and syringe (NS) sales and their
      attitudes toward a needle exchange program through a telephone survey of 75
      randomly selected pharmacies in Baltimore, Maryland, where possession of drug
      paraphernalia is illegal but where NS can be purchased without a prescription.
      Pharmacists' (n=46) procedures for NS sales included asking for picture
      identification (54%), requiring a prescription (34%), or requiring a diabetic
      identification (DID, 34%) for NS purchase; multiple responses were allowed. The
      median number of prescription and nonprescription NS sold per month was 950. Most
      (86.6%) pharmacists reported selling NS without prescriptions at their
      discretion. Pharmacists sold a median of 16 nonprescription NS per month.
      Pharmacists who required prescriptions or DID (56.5%) sold nonprescription NS
      significantly less often than those who did not require prescriptions or DID
      (p=.007). Most pharmacists (87%) were aware of the needle exchange program, 78.3%
      supported the program, and 67.4% supported selling nonprescription NS in
      pharmacies. Although there was no difference in anticipated effects of needle
      exchange or in support for needle exchange between pharmacists who did or did not
      require prescriptions, DID, or both, pharmacists who did require these items were
      significantly less likely to support pharmacy sales of nonprescription NS than
      pharmacists with less restrictive sales policies (p=.04). Although most
      pharmacists surveyed supported access to sterile NS by injection drug users
      through a needle exchange program, there was a diversity of approaches to
      nonprescription NS sales among pharmacists in a city that does not require
      prescriptions for access to sterile NS. Most supported nonpharmacy needle
      exchange programs, and more than one half limited injection drug users' access to
      NS through restrictive sales practices. To reduce injection drug users' exposure
      to HIV, pharmacists should be educated about HIV prevention and injection drug
      use and be included in development of HIV prevention programs, including legal
      pharmacy NS sales.

PMID- 9663631
TI  - Access to sterile syringes in Maine: pharmacy practice after the 1993 repeal of
      the syringe prescription law.
AB  - In October 1993, the Maine legislature repealed the prescription law regulating
      the sale of syringes. The new law allowed but did not require licensed
      pharmacists to dispense syringes without a prescription to anyone 18 years of age
      or older. From November 1995 to January 1996, we conducted a telephone survey of
      208 Maine pharmacists to evaluate the sale of syringes with and without a
      prescription and to assess pharmacists' willingness to sell syringes without a
      prescription. We found that 94% of pharmacists were willing, in all cases or at
      the discretion of the pharmacist, to sell syringes without a prescription.
      However, when asked specifically about willingness to sell syringes without a
      prescription to suspected injection drug users (IDUs) > or =18 years of age, 47%
      were willing, 40% were not willing, and 13% did not know or declined to answer.
      Pharmacists reported other requirements for the purchase of syringes without a
      prescription, such as the requirement for the customer to provide a reasonable
      justification for the purchase. In all, there were 31 (15%) pharmacists in the
      sample willing to sell syringes to without a prescription with no additional
      requirements for purchase to suspected IDUs as permitted by law. There were few
      negative incidents reported involving IDUs and the sale of syringes without a
      prescription since amendment of the law. Although sales of syringes without a
      prescription were reported, the numbers sold fell short of the estimated number
      of syringes required for IDUs in Maine to use a new syringe for every injection.
      Despite the change in the prescription law intended to increase access to
      syringes, the data suggest barriers such as drug paraphernalia laws and pharmacy
      policies may prevent IDUs from purchasing syringes and contribute to ongoing
      transmission of HIV. Amendment of the drug paraphernalia and syringe possession
      laws, clarification of the legitimate medical purpose of access to sterile
      syringes for IDUs, and offering pharmacists continuing education on the
      prevention of blood-borne disease appear to be necessary steps in the effort to
      decrease the transmission of HIV among IDUs in Maine.

PMID- 9663632
TI  - Impact of the change in Connecticut syringe prescription laws on pharmacy sales
      and pharmacy managers' practices.
AB  - We assessed the impact of the 1992 change in Connecticut syringe prescription
      laws on pharmacy sales and pharmacy managers' sales practices. A mail survey was
      conducted in 1994 of all current pharmacy managers in the five largest cities in
      Connecticut (Hartford, New Haven, Waterbury, Bridgeport, and Stamford) and a
      random sample of those practicing in all other areas. Of these, 89.3% of the
      pharmacies in the five largest cities and 85.1% in the other areas had ever sold
      syringes without a prescription since the July 1992 law went into effect. Most
      pharmacists identified safety issues as very important in their personal decision
      about the sale of syringes without a prescription. Although the purpose of the
      change in the prescription law was to provide expanded access to sterile syringes
      by injection drug users (IDUs), only 31.4% of the managers who were allowed to
      sell in all instances and 18.1% of those who sold at their discretion were very
      willing to sell syringes to IDUs. In the logistic regression model of pharmacies
      with a sell-in-all-instances policy, the perceived benefit of the sale of
      syringes on health and community well-being was the only influence independently
      associated with managers support for nonprescription sales. Overall, managers
      reported they did not know what other pharmacists thought (40.4%) or did (42.9%)
      regarding the sale of syringes. When pharmacists had discretion over syringe
      sales, managers' beliefs about what other Connecticut pharmacists thought and did
      about the nonprescription sale of syringes remained a significant influence on
      the degree of support for sales. Most pharmacies implemented and maintained
      policies permitting the sale of syringes without a prescription. Several issues,
      including risk of discarded contaminated syringes around pharmacies and in the
      community and reluctance to sell to IDUs, reduced pharmacists willingness to sell
      syringes. Efforts to incorporate pharmacists as active partners in HIV prevention
      in IDUs should promote the sale of syringes without a prescription to IDUs as
      acceptable public health practice.

PMID- 9663633
TI  - Community-based programs for safe disposal of used needles and syringes.
AB  - OBJECTIVES: To review issues related to discarded syringes in the community and
      to describe community-based programs for the safe disposal of used needles and
      syringes. METHODS: We used the medical literature and chain referral to identify
      community-based syringe disposal programs other than syringe exchange programs
      (SEPs). We held a workshop in June 1996 involving staff from disposal programs;
      manufacturers of syringes, sharps containers, and other disposal devices; solid
      waste companies; public health staff; and researchers. RESULTS: Fifteen programs
      for the safe disposal of syringes were identified in the United States, Canada,
      and Australia. Of these, 12 primarily served persons with diabetes who use
      insulin, and 3 primarily served injection drug users (IDUs). The programs used
      three major strategies: puncture-resistant containers discarded in trash,
      community drop boxes, and sharps containers turned in for biohazard disposal at
      community sites, hospitals, or pharmacies. Participants in the workshop described
      key points in developing syringe disposal programs. Programs should involve
      pharmacists, physicians, waste disposal companies, public health departments,
      hospitals, diabetes educators, persons with diabetes who use insulin, and IDUs.
      For IDUs, criminal penalties for possession of syringes are a substantial
      deterrent to participation in community efforts to safely dispose of used
      syringes. The multiple and sometimes conflicting local, state, and federal laws
      and regulations concerning medical waste hinder development of multistate or
      national approaches to the safe disposal of syringes. More information is needed
      on community-based syringe disposal programs. CONCLUSION: Communities in the
      United States, Canada, and Australia have developed different approaches to
      achieve safe disposal of used syringes.

PMID- 9663634
TI  - Operation Red Box: a pilot project of needle and syringe drop boxes for injection
      drug users in East Baltimore.
AB  - We assessed the acceptability and the use of a community-based needle and syringe
      disposal project designed to serve injection drug users. In June 1996, three
      surplus U.S. mail collection boxes were painted red and used as syringe and
      needle drop boxes in locations with high drug use in East Baltimore. Acceptance
      of the drop boxes was measured by focus groups of residents, drug users, and
      police, held before and after project implementation. Use was measured by weekly
      counts of needles recovered from the red boxes. A sample of all deposited needles
      was randomly chosen for needle washing and subsequent HIV antibody testing.
      Community impact was measured by systematic surveys of needles discarded on
      public sidewalks, in areas with and areas without drop boxes. Before
      implementation, members of focus groups expressed concerns that drop boxes could
      convey mixed messages to youth (e.g., seeming to condone drug use), might result
      in increased loitering, and could further community stigmatization. After project
      implementation, all focus groups expressed support of project expansion. In the
      first 10 months, 2971 needles were collected. Of 156 needles tested, 10.9% were
      positive for HIV antibody. Needle counts on the street showed no significant
      change in red box areas compared with control areas. In this pilot project, red
      boxes were accepted by the community and drug users. Police officers also used
      the boxes to dispose of confiscated needles. Although limited in the number of
      drop boxes and follow-up time, this pilot project shows promise as a community
      based method of safe needle disposal.

PMID- 9663635
TI  - An economic analysis of needle exchange and pharmacy-based programs to increase
      sterile syringe availability for injection drug users.
AB  - Our objectives were to estimate the cost per syringe distributed for five syringe
      distribution strategies (a needle exchange program [NEP], a pharmacy-based NEP,
      free pharmacy distribution of pharmacy kits, sale of such pharmacy kits to
      injection drug users [IDUs], and sale of syringes in pharmacies); to assess the
      total costs of these strategies; and to conduct an economic analysis of these
      strategies in preventing HIV infection in IDUs. We estimated the costs for NEPs
      by using data from previous research; costs for the four pharmacy-based
      strategies were resource-based. Using estimates of the number of syringes
      required to provide a sterile syringe for each IDU injection, we estimated the
      total costs of the strategies in three representative U.S. cities. The lifetime
      cost of treating a person for HIV infection, discounted into current value, was
      used to estimate the number of syringes that could be distributed for that amount
      by the five strategies and thus the number of IDUs who could be ensured a sterile
      syringe for each injection. We then conducted a threshold analysis for
      calculating the annual HIV seroincidence for the program to be cost-neutral. The
      cost per syringe distributed in U.S. dollars was $0.97 for the NEP, $0.37 for the
      pharmacy-based NEP, $0.64 for pharmacy kit distribution, $0.43 for pharmacy kit
      sale, and $0.15 for syringe sale. The total annual cost in U.S. dollars of
      providing 50% of the syringes needed for a single syringe for every injection
      ranged from $6 to $40 million for New York City, from $1 to $6 million for San
      Francisco, and from $30,000 to $200,000 for Dayton, Ohio. The annual HIV
      seroincidence for the program to be cost-neutral compared with the cost of
      medical treatment for HIV injections was 2.1% for the NEP, 0.8% for the pharmacy
      NEP, 1.4% for pharmacy kit distribution, 0.9% for pharmacy kit sale, and 0.3% for
      syringe sale. All five strategies could distribute syringes at relatively low
      unit costs; NEPs would be the most expensive and syringe sales would be the
      cheapest. At annual seroincidences exceeding 2.1%, all strategies are likely to
      be cost-saving to society.

PMID- 9663636
TI  - Cost and cost-effectiveness of increasing access to sterile syringes and needles
      as an HIV prevention intervention in the United States.
AB  - We determined the cost of increasing access of injection drug users (IDUs) to
      sterile syringes and needles as an HIV prevention intervention in the United
      States and the cost per HIV infection averted by such a program. We considered a
      hypothetical cohort of 1 million active IDUs in the United States. Standard
      methods were used to estimate the cost and cost-effectiveness of policies to
      increase access to sterile syringes and syringe disposal at various levels of
      coverage (e.g., a 100% coverage level would ensure access to a sterile syringe
      for each injection given current levels of illicit drug injection in the United
      States; a 50% coverage level would ensure access to one half of the required
      syringes). A mathematical model of HIV transmission was employed to link
      programmatic coverage levels with estimates of numbers of HIV infections averted.
      A policy of funding syringe exchange programs, pharmacy sales, and syringe
      disposal to cover all illicit drug injections would cost just over $423 million
      U.S. for 1 year. One third of these costs would be paid for as out-of-pocket
      expenditures by IDUs purchasing syringes in pharmacies. Compared with the status
      quo, this policy would cost an estimated $34,278 U.S. per HIV infection averted,
      a figure well under the estimated lifetime costs of medical care for a person
      with HIV infection. At very high levels of coverage (>88%), the marginal cost
      effectiveness of increased program coverage becomes less favorable. Although the
      total costs of funding large-scale IDU access to sterile syringes and disposal
      seem high, the economic benefits are substantial. Even at high levels of
      coverage, such funding would save society money. As part of a comprehensive
      program of HIV prevention, policies to increase IDUs access to sterile syringes
      urgently need further consideration by public health decision makers.

PMID- 9663637
TI  - Following the blood: syringe reuse leads to blood-borne virus transmission among
      injection drug users.

PMID- 9663638
TI  - Strict syringe laws in Rhode Island are associated with high rates of reusing
      syringes and HIV risks among injection drug users.

PMID- 9663639
TI  - In New York City, syringe laws and regulations deter physicians and pharmacists
      from prescribing and selling syringes to persons who may be injection drug users.

PMID- 9663640
TI  - Deregulation of syringes and needles for medical use and to prevent the spread of
      blood-borne pathogens among illicit injection drug users.

PMID- 9663641
TI  - Oregon's exclusion of syringes from its 1987 drug paraphernalia law was an HIV
      prevention measure.

PMID- 9663642
TI  - Maine removed criminal penalties for syringe possession in 1997 after allowing
      sale of syringes without a prescription in 1993.

PMID- 9663643
TI  - Peer education of pharmacists and supplying pharmacies with IDU packets to
      increase injection drug users' access to sterile syringes in Connecticut.

PMID- 9663644
TI  - Needle hygiene and sources of needles for injection drug users: data from a
      national survey.

PMID- 9663645
TI  - oPer1 is an early response gene under photoperiodic regulation in the ovine pars
      tuberalis.
AB  - Mammalian Per1 (or RIGUI) is a recently described putative clock gene that is
      expressed in the suprachiasmatic nucleus. It is also expressed in the pars
      tuberalis (PT) of the pituitary, where melatonin appears to drive its expression.
      This study examines the regulation of Per1 expression. In ovine PT cells, oPer1
      is an early response gene transiently expressed after stimulation with forskolin,
      but melatonin has no independent effect on its expression. In sheep, PT tissue
      photoperiodic background influences the magnitude or timing of expression of
      oPer1 2 h after lights-on. These data demonstrate that oPer1 mRNA is elevated in
      the PT following the decline in night-time melatonin, and that the amplitude or
      timing of this elevation is dependent upon the duration of the nocturnal
      melatonin signal.

PMID- 9663646
TI  - Stimulatory effect of calcitonin gene-related peptide on adrenocorticotropin
      release from rat anterior pituitary cells.
AB  - In the present study, we examined the direct regulatory effect of rat calcitonin
      gene-related peptide (CGRP) on adrenocorticotropin (ACTH) release from rat
      cultured anterior pituitary cells. CGRP significantly increased ACTH release at
      concentrations of 10(-8)-10(-11) M. The ACTH release was gradually increased by
      CGRP concentrations lower than 10(-10) M, and was decreased at concentrations
      higher than 10(-9) M, presenting a bell-shaped dose-response curve. As well as
      having an additive effect on corticotropin-releasing factor-induced ACTH release,
      CGRP stimulated the accumulation of intracellular cAMP. The CGRP-induced ACTH
      release was inhibited by a protein kinase A inhibitor, suggesting that its
      stimulatory effect on the ACTH release was mediated via an adenylate-cyclase
      protein kinase system. CGRP-like immunoreactive nerve fibers have been reported
      to innervate the anterior pituitary, so that the stimulatory effect of CGRP on
      the ACTH release suggests that this peptide may be involved in neural regulation
      of hormone secretion in the anterior pituitary.

PMID- 9663647
TI  - Consequences of prenatal morphine exposure on the hypothalamo-pituitary-adrenal
      axis in the newborn rat: effect of maternal adrenalectomy.
AB  - The hypothalamo-pituitary-adrenal axis is already functional in rat fetuses in
      late gestation. We have reported previously that prenatal morphine exposure
      induced a severe atrophy of the adrenals and a decrease of corticosterone release
      in newborn rats at birth and during the early postnatal period. The first aim of
      the present study was to determine the effects of prenatal morphine exposure (1)
      on corticotrophin releasing factor (CRF) content of the hypothalamus, CRF
      immunofluorescence in the median eminence, CRF mRNA in the paraventricular
      nucleus (PVN) and pro-opiomelanocortin (POMC) mRNA in the anterior pituitary
      gland; (2) on CRF-induced ACTH release from the anterior pituitary gland in
      vitro; and (3) on ACTH-induced corticosterone release by the adrenals in vitro.
      Moreover, as morphine is a hepatotoxic factor, we determined the effects of
      prenatal morphine on liver weight and plasma corticosteroid binding globulin
      (CBG) binding capacity in newborn rats. Since acute administration of morphine
      stimulates corticosterone secretion in adult rats and since maternal
      corticosterone can cross the placental barrier, we also measured both adrenal
      weight and glucocorticoid activity in newborns from adrenalectomized mothers
      treated with morphine. The present results show that prenatal morphine given to
      intact mothers induced adrenal atrophy and hypoactivity in newborns but did not
      affect the responsiveness of the anterior pituitary gland to CRF or that of the
      adrenal gland to ACTH. Prenatal morphine reduced both CRF content in the newborn
      hypothalamus and CRF immunofluorescence in the median eminence without a
      significant effect on CRF mRNA expression in the PVN. Moreover, morphine induced
      a significant decrease of POMC mRNA in the anterior pituitary gland. However,
      morphine did not significantly affect the weight of the liver, or the plasma CBG
      binding capacity for corticosterone, in rat pups. In contrast, morphine treatment
      of the adrenalectomized mothers did not induce adrenal atrophy in newborns and
      did not impair adrenal activation during the early postnatal period. Maternal
      adrenalectomy also prevented the effects of prenatal morphine on hypothalamic
      content of CRF, CRF immunofluorescence in the median eminence, and POMC mRNA in
      the anterior pituitary gland. However, adrenal atrophy was observed at term in
      newborns of adrenalectomized mothers treated with both morphine and
      corticosterone or only corticosterone. In conclusion, morphine given to pregnant
      rats induced inhibition of the hypothalamo-pituitary-adrenal axis in pups at
      term. As maternal adrenalectomy prevented these effects, we speculate that an
      adrenal factor of maternal origin, probably corticosterone, mediated these drug
      effects on newborns.

PMID- 9663648
TI  - Effect of short photoperiods on the in vitro GnRH release by hypothalamic
      explants in intact and castrated male Syrian hamsters: relation to testicular
      regression and recrudescence.
AB  - Prolonged exposure of adult Syrian hamsters to short days decreases LH and FSH
      circulating levels within 2-4 weeks, then induces testicular regression. After 18
      weeks of short days, the testis size and gonadotropin levels increase
      spontaneously. This study investigated whether these phases of photosensitivity
      and photorefractoriness corresponded to variations of in vitro GnRH release. Male
      hamsters were either kept under long days (LD 16:8) or transferred to short days
      (SD 6:18) and sacrificed from 2-26 weeks after transfer. To separate the effects
      of testis feedback from a possible direct photoperiodic drive on the
      hypothalamus, males were bilaterally castrated, kept under LD or transferred to
      SD, and sacrificed from 2-14 weeks after transfer. Hypothalamic explants were
      incubated in a saline buffer for three periods of 15 min and exposed to KCl (60
      mM) for 15 min. The return to basal values was followed for six periods of 15
      min, then the explants were stimulated with copper complexed equimolarly with
      histidine (Cu/His, 200 microM) and prostaglandin E2 (PGE2, 10 microM). At the end
      of the incubation period, the concentration of GnRH remaining in the explants was
      measured. In intact males, GnRH release in vitro increased significantly between
      2 and 4 weeks after transfer to short days; it returned to values similar to LD
      ones between 6 and 12 weeks, during the phase of testis involution. At the
      beginning of photorefractoriness (SD 14-18), it increased transiently and
      returned to values similar to LD ones from SD 20, during the testis spontaneous
      recrudescence. After castration, the in vitro GnRH release decreased
      significantly under LD and SD. The transfer of castrated hamsters to SD resulted
      in transient increases of GnRH release (SD 4, 8 and 14), and in a progressive
      loss of the explant's ability to release GnRH in vitro. These results showed a
      photoperiodic regulation of in vitro GnRH release and a testis feedback effect on
      this release. They demonstrated an inverse relationship between the readily
      releasable pool of GnRH and the circulating levels of gonadotrophins at the
      beginning of photosensitive and photorefractory phases and after castration.

PMID- 9663649
TI  - Influence of nitric oxide synthase inhibitors on the ACTH and cytokine responses
      to peripheral immune signals.
AB  - Nitric oxide (NO) is an unstable gas that participates in the response of the
      hypothalamic-pituitary-adrenal (HPA) axis to a variety of immune signals,
      including turpentine-induced tissue damage and the systemic injection of the pro
      inflammatory cytokine interleukin 1-beta (IL-1beta). Studies that have
      investigated the role of this gas in the intact rat have relied on blockade of NO
      formation with the NO synthase (NOS) inhibitor N(omega)nitro-L-arginine
      methylester (L-NAME). They have suggested that endogenous NO blunts the ACTH
      response to intravenous (i.v.) IL-1beta in part by exerting an inhibitory
      influence on the release of hypothalamic peptides such as corticotropin-releasing
      factor (CRF) from nerve terminals in the median eminence. It must nevertheless be
      noted that, at present, evidence for this mode of action remains circumstantial.
      Significant controversy remains regarding the specificity of the compounds used
      to block NO formation, the characteristics of their effect in terms of dose and
      timing of administration, the possibility that their effect is restricted to IL
      1beta or can be expanded to other pro-inflammatory cytokines, and the question of
      whether the possibility that they might also influence ACTH release by altering
      circulating levels of tumor necrosis factor-alpha (TNF-alpha) and IL-6. The
      purpose of the present study was to elucidate these points. In the first series
      of experiments, we determined the i.v. IL-1beta-induced ACTH response to various
      doses of systematically injected L-NAME (1-100 mg/kg). At 10-100, but not 1
      mg/kg, L-NAME significantly (P<0.01) augmented the ACTH response to IL-1beta,
      with a maximum effect observed at 30 and 100 mg/kg. At the 30 mg/kg dose, L-NAME
      was equally effective in augmenting the ACTH response when administered between 5
      and 240 min prior to the cytokine. The effect of L-NAME was fully mimicked by
      equivalent doses of other arginine derivatives such as N(omega)-monomethyl-L
      arginine (L-NMMA) or N(omega)-nitro-L-arginine (L-NNA), indicating that
      controversy in the published literature concerning the influence of NO on CRF
      secretion does not appear to be due to the use of different arginine derivatives.
      The ability of other cytokines such as TNF-alpha and IL-6 to release ACTH and
      corticosterone was significantly (P<0.01) augmented by blockade of NO formation
      in a manner similar to that found with IL-1beta. To test the hypothesis that L
      NAME might alter ACTH secretion at least in part by modifying the secretion of
      pro-inflammatory cytokines, we measured plasma concentrations of TNF-alpha and IL
      6 following endotoxin injection in the presence or absence of L-NAME. Blockade of
      NO formation reduced TNF-alpha but increased IL-6 levels in rats administered the
      lipopolysaccharide (25 microg/kg i.v.). As L-NAME augments the ACTH response to
      TNF-alpha as well as IL-6, it is improbable that changes in TNF-alpha and IL-6
      secretion during immune stimulation represents an important mechanism mediating
      the inhibitory influence of endogenous NO on the HPA axis activity. Collectively,
      these results indicate that the systemic injection of L-NAME very quickly
      augments the stimulatory effect of pro-inflammatory cytokines on ACTH secretion,
      and does so for at least 4 h. Other arginine derivatives known to block the
      activity of constitutive NO syntheses, such as L-NMMA and L-NNA, exert an effect
      that is virtually identical to that of L-NAME. The ability of L-NAME to increase
      the ACTH response to i.v. IL-1beta is also observed in rats injected with TNF
      alpha and IL-6. Because of the opposite effects of L-NAME on the levels of these
      two cytokines, the influence of arginine derivatives on ACTH release is probably
      not due to changes in cytokines produced during immune stimulation such as
      endotoxemia.

PMID- 9663650
TI  - Interaction between glucocorticoids and corticotropin releasing hormone (CRH) in
      the regulation of the pituitary CRH receptor in vivo in the rat.
AB  - Acute stress causes biphasic changes in corticotropin releasing hormone (CRH)
      receptor mRNA expression with an early decrease followed by an increase. However,
      in the absence of glucocorticoids in adrenalectomized rats, stress results in
      prolonged CRH receptor (CRH-R) mRNA loss, suggesting that interactions between
      glucocorticoids and hypothalamic factors are critical for regulation of CRH
      receptor mRNA. To address this question, CRH binding, type-1 CRH-R mRNA, POMC
      mRNA and POMC hnRNA expression were measured by binding autoradiography and in
      situ hybridization in pituitaries from intact and adrenalectomized rats. CRH-R
      mRNA decreased by 59% 5 h after injection of corticosterone (10 mg s.c.) and
      returned to basal levels by 18 h, a time when plasma corticosterone
      concentrations were still elevated, and CRH binding and POMC hnRNA were
      significantly reduced. Elevations in plasma corticosterone in the range of acute
      stress by injection of 2 mg s.c. caused CRH-R mRNA expression to return to near
      basal values by 6 h, after a 52% and 39% decrease at 2 h and 4 h. More transient
      changes were seen after a single injection of CRH (1 microg), with a 44% decrease
      in CRH-R mRNA and a 175% increase in POMC hnRNA by 2 h, returning to basal values
      by 4 h. The transient effect of CRH was not due to clearance of CRH from the
      circulation or receptor desensitization since CRH receptor mRNA expression also
      recovered after injection of a higher dose (10 microg) or repeated injections of
      CRH which caused sustained increases in plasma CRH and pituitary POMC hnRNA
      levels. CRH injection in adrenalectomized rats decreased CRH-R mRNA for up to 6
      h, suggesting that glucocorticoids are permissive for the recovery of CRH-R mRNA.
      Supporting this hypothesis, simultaneous injection of corticosterone and CRH
      restored CRH-R mRNA expression by 4 h, and increased CRH binding 4 h and 6 h
      after injection. The data show that interaction between CRH and glucocorticoids
      counteracts individual inhibitory effects of these regulators alone, and that
      such effects are likely to contribute to the regulatory pattern of pituitary CRH
      receptors during acute stress.

PMID- 9663651
TI  - Intratesticular serotonin affects steroidogenesis in the rat testis.
AB  - The effect of intratesticular administration of serotonin (5-HT), ketanserin (5
      HT2 receptor antagonist), and 5,7-dihydroxytryptamine (5,7-DHT) (the neurotoxin
      that destroys serotoninergic neural elements) on steroidogenesis was studied in
      immature and adult rats. In adults, bilateral intratesticular injection of 5-HT
      resulted in a significant decrease in basal but not in hCG-stimulated
      testosterone secretion and in serum testosterone concentration, whereas
      ketanserin induced a significant rise in steroidogenesis 1 h post-treatment.
      There was no effect 1 day after administration of 5-HT or ketanserin, and 7 days
      after the injection of 5,7-DHT. In immature rats 1 day after bilateral testicular
      administration of ketanserin, basal testosterone secretion in vitro was
      significantly suppressed. In immature hemicastrates, local injection of 5-HT
      resulted (1 day post-treatment) in a significant rise in steroidogenesis while
      administration of 5,7-DHT decreased testosterone secretion 7 days after the
      injection of the neurotoxin. The results indicate that in adult rats 5-HT exerts
      a suppressive, whereas in immature rats, a stimulatory action on steroidogenesis
      occurs. Data also suggest that, in both age groups, the effect of 5-HT is
      mediated through 5-HT2 receptors. The observation that in immatures
      administration of the neurotoxin resulted in an effect similar to that found
      following the treatment with the receptor antagonist suggests that, in this age
      group, 5-HT derived from local neural elements might also be involved in the
      control of 5-HT on Leydig cell steroidogenesis.

PMID- 9663652
TI  - Glutamate pathways mediate somatostatin responses to glucose in normal and
      diabetic rat hypothalamus.
AB  - We investigated the role of hypothalamic glutamate receptors in mediating the
      stimulatory effect of low glucose (< 5 mM) on somatostatin release. We also
      studied whether alteration in glutamate release might contribute to the reduced
      hypothalamic somatostatin response to low glucose observed in diabetic (Goto
      Kakizaki) rat hypothalami. Hypothalamic somatostatin release in response to
      incubation with 1 mM D-glucose was inhibited by the ionotropic glutamate receptor
      antagonists MK801, D-AP5 and DNQX but not by the metabotropic antagonists L-AP3
      or MCPG. The release of somatostatin was increased by the ionotropic agonists
      NMDA, AMPA and kainate but not by metabotropic agonists t-ACPD or L-AP4. Basal
      and peak glutamate release in response to incubation with 1 mM glucose, were
      significantly lower from GK hypothalami There were no significant differences in
      the basal or stimulated release of serine and GABA. These data indicate that
      ionotropic NMDA/AMPA/kainate receptors and not metabotropic receptors mediate the
      effects of glucose on rat hypothalamic somatostatin release. Reduced hypothalamic
      somatostatin release in response to low glucose in diabetic (Goto-Kakizaki) rats
      may well be secondary, at least in part, to reduced glutamate release.

PMID- 9663653
TI  - Ionotropic and metabotropic glutamate receptor agonist-induced [Ca2+]i increase
      in isolated rat supraoptic neurons.
AB  - In the present study, the effects of glutamate and of agonists for ionotropic and
      metabotropic glutamate receptors on intracellular Ca2+ concentration ([Ca2+]i)
      were investigated in neurons of the rat supraoptic nucleus (SON). We used the
      intracellular Ca2+ imaging technique with fura-2, in single magnocellular neurons
      dissociated from the SON of rats. Glutamate (10(-6)-10(-4) M) evoked a dose
      dependent increase in [Ca2+]i. The glutamate agonists exerted similar effects,
      although with some differences in the characteristics of their responses. The
      [Ca2+]i response to NMDA was smaller than those of glutamate or the non-NMDA
      receptor agonists, AMPA and kainate, but was significantly enhanced by the
      removal of extracellular Mg2+. Glutamate, as well as quisqualate, an agonist for
      both ionotropic and metabotropic glutamate receptors, evoked a [Ca2+]i increase
      in a Ca2+-free condition, suggesting Ca2+ release from intracellular Ca2+ stores.
      This was further evidenced by [Ca2+]i increases in response to a more selective
      metabotropic glutamate receptor agonist, t-ACPD, in the absence of extracellular
      Ca2+. Furthermore, the quisqualate-induced Ca2+ release was abolished by the
      selective metabotropic glutamate receptor antagonist, (S)-4-carboxyphenylglycine.
      The results suggest that metabotropic glutamate receptors as well as non-NMDA and
      NMDA receptors are present in the SON neurons, and that activation of the first
      leads to Ca2+ release from intracellular Ca2+ stores and the activation of the
      latter two types induces Ca2+ entry. These dual mechanisms of Ca2+ signalling may
      play a role in the regulation of SON neurosecretory cells by glutamate.

PMID- 9663654
TI  - Inhibition of naloxone-stimulated adrenocorticotropin release by alprazolam in
      myotonic dystrophy patients.
AB  - Myotonic dystrophy (DM) is an autosomal dominant disorder causing myotonia,
      progressive muscle weakness, and endocrine abnormalities including hypothalamic
      pituitary-adrenal (HPA) axis hyperresponsiveness to CRH-mediated stimuli. This
      ACTH hyperresponsiveness appears directly related to the underlying genetic
      abnormality. Naloxone (Nal)-mediated CRH release causes ACTH release in normal
      humans and an ACTH hyperresponse in DM. Alprazolam (APZ) attenuates the ACTH
      release in response to Nal in normal individuals, probably by inhibiting CRH
      release. This study investigates the effects of APZ on Nal-induced HPA axis
      stimulation in DM. The ACTH response to Nal in DM subjects was significantly
      reduced by APZ. Despite this DM patients have a relative resistance to APZ
      inhibition of Nal-induced ACTH/cortisol release. APZ caused a smaller percentage
      reduction in AUC for ACTH in DM compared with controls. These findings provide
      further insight into the mechanism(s) of the HPA axis abnormalities in DM. In DM,
      there may be an increase in tonic opioid inhibition to CRH release with
      compensatory increases in stimulatory pathways. Alternatively, these patients may
      have a basal increase in pituitary vasopressin levels or an enhanced AVP/CRH
      synergistic mechanism at the level of the corticotroph.

PMID- 9663655
TI  - Growth phase coupled modulation of Escherichia coli ribosomes.
AB  - Ribosomal modulation factor (RMF), a small basic protein, expresses
      transcriptionally in the stationary phase of Escherichia coli cells and binds to
      50S ribosomal subunits. The RMF bound 70S ribosomes dimerize to form 100S
      particles that have no translational activity. In transferring the stationary
      cells to a fresh medium, the 100S particles release the RMF and dissociate to
      active 70S. The interconversion of ribosomes between active 70S and inactive 100S
      by RMF is a cellular mechanism controlling translation.

PMID- 9663656
TI  - Abortive recombination in Escherichia coli ruv mutants blocks chromosome
      partitioning.
AB  - BACKGROUND: All the ruvA, ruvB and ruvC mutants of Escherichia coli are sensitive
      to treatments that damage DNA, and are mildly defective in homologous
      recombination. It has been reported that the ruv mutants form nonseptate,
      multinuclear filaments after low doses of UV irradiation, dependent on the sfiA
      gene product. In vitro, the RuvAB complex promotes the branch migration of
      Holliday junctions, and RuvC resolves the junctions endonucleolytically. RESULTS:
      After a low UV dose (5 J/m2), both delta ruvAB and delta ruvC mutant cells became
      filamentous, with their chromosomes aggregated in the central region. This
      corresponded to an increase in nonmigrating DNA on pulsed field gel
      electrophoresis of the XbaI digested chromosome. Upon further incubation, they
      produced a large number of anucleoid cells of normal size. A recA mutation, but
      not a recB mutation, suppressed these phenotypes of the ruv mutants. The ruv
      polA12(Ts) double mutants were inviable at the nonpermissive temperature and
      mimicked the morphological phenotypes of the UV irradiated ruv mutants.
      CONCLUSION: ruvA, B and C mutations block chromosome partitioning in UV
      irradiated cells because the abortive homologous recombination covalently links
      chromosomes together. There is a recBCD independent pathway for the recA
      dependent formation of recombination intermediates. An Ruv-mediated resolution of
      recombination intermediates is required for the repair of strand breaks produced
      in UV irradiated cells and in the polA mutant cells.

PMID- 9663657
TI  - The resolvase encoded by Xanthomonas campestris transposable element ISXc5
      constitutes a new subfamily closely related to DNA invertases.
AB  - BACKGROUND: Conservative site-specific recombination is responsible for the
      resolution of cointegrates which result during the transposition of class II
      transposable elements. Resolution is catalysed by a transposon-encoded
      recombinase, resolvase, that belongs to a large family of recombinases, including
      DNA invertases. Resolvases and the related invertases are likely to employ
      similar reaction mechanisms during recombination. There are important
      differences, however. Resolvases require two accessory DNA binding sites within
      each of the two directly repeated recombination sites. Invertases instead need a
      host factor, Fis, and an enhancer type DNA sequence, in addition to two inversely
      orientated recombination sites. RESULTS: The resolvase encoded by transposable
      element ISXc5 from the gram-negative phytopathogen Xanthomonas campestris shows
      two features which distinguish it from other known resolvases. First, it is more
      closely phylogenetically related to invertases than other resolvases. In
      particular, two functionally important regions seem highly conserved between this
      resolvase and members of the invertase subfamily. Second, the enzyme exhibits a
      large extension of its carboxy-terminal domain with unknown function. We purified
      ISXc5 resolvase and analysed its resolution reaction in vitro. Our biochemical
      and DNA topological analysis reveals that critical features of resolution are
      similar, if not identical, to that carried out by gammadelta resolvase. However,
      despite its apparent similarity to invertases, we were unable to detect
      recombination on standard substrates for DNA inversion, in either the presence or
      absence of Fis. CONCLUSIONS: ISXc5 resolvase employs a reaction mechanism which
      is common to members of the resolvase family. Its position near the evolutionary
      borderline to invertases and its high degree of identity within two functionally
      important regions with members of the DNA invertase subfamily suggest that only a
      few replacements of critical residues may suffice to convert this resolvase into
      a functional, possibly Fis-dependent invertase.

PMID- 9663658
TI  - recessive spotting: a linked locus that interacts with W/Kit but is not allelic.
AB  - BACKGROUND: The murine coat-colour mutation recessive spotting (rs) maps very
      closely to the W/Kit locus, encoding the proto-oncoprotein Kit, the protein
      tyrosine kinase receptor for stem cell factor. Kit is important in the
      development of melanocytes, germ cells, interstitial cells of Cajal (ICC) and
      haemopoietic lineages, including mast cells. rs has never been genetically
      separated from Kit, and interacts with Kit mutations, suggesting that it is a
      recessive allele of Kit. Here we have tested this possibility. We have shown
      previously that diploid rs/rs melanocytes proliferated more slowly than did +/+
      melanocytes, as did an immortal line of rs/rs melanocytes, melan-rs. RESULTS: The
      Kit mRNA level in rs/rs melanocytes was indistinguishable from that of other
      melanocyte lines. The Kit cDNA sequence from rs/rs melanocytes and the kinase
      activity of Kit in rs/rs mast cells appeared to be normal. No deficiency of mast
      cells or ICC was observed in rs/rs mice. Moreover, following the overexpression
      of a normal Kit cDNA, proliferation of rs/rs melanocytes was retarded further,
      but that of +/+ melanocytes was increased, indicating an intracellular
      interaction between rs and Kit. Of other closely linked tyrosine kinase genes,
      melanocytes and melanoblasts did not express mRNA for Pdgfra, Flk-1 or Txk, but
      both expressed Tec, encoding a nonreceptor kinase that interacts with Kit.
      CONCLUSIONS: rs is not a mutation in Kit, although we have confirmed that rs
      interacts with Kit. It seems unlikely that rs affects Pdgfra, Flk-1 or Txk, but
      Tec remains a candidate for rs.

PMID- 9663659
TI  - Epigenetic reprogramming of the human H19 gene in mouse embryonic cells does not
      erase the primary parental imprint.
AB  - BACKGROUND: Genomic imprinting in mammals is thought to result from epigenetic
      modifications to chromosomes during gametogenesis, which leads to differential
      allelic expression during development. There is a requirement for an appropriate
      experimental system to enable the analysis of the mechanisms of genomic
      imprinting during embryogenesis. RESULTS: To develop a novel in vitro system for
      studying the molecular basis of genomic imprinting, we constructed mouse cell
      lines containing either a paternal or maternal human chromosome 11, by microcell
      mediated chromosome transfer. Allele-specific expression and DNA methylation
      studies revealed that the imprinting status of the human H19 gene was maintained
      in mouse A9 mono-chromosomal hybrids. Each parental human chromosome was
      introduced independently into mouse near-diploid immortal fibroblasts (m5S) and
      two embryonal carcinoma (EC) cell lines (OTF9-63 and P19). The paternal allele of
      human H19 remained in a repressed state in m5S cells, but was de-repressed in
      both EC cells. The paternal H19 allele was demethylated extensively in OTF9-63
      cells, whereas the only alteration in P19 hybrids was de novo methylation on both
      alleles in the 3' region. Following in vitro differentiation, the expressed
      paternal H19 allele was selectively repressed in differentiated derivatives of EC
      hybrids. CONCLUSION: These results indicated that human imprint marks could
      function effectively in mouse cells, and that the imprinting process was
      epigenetically reprogrammed in embryonal carcinoma cells, without erasure of the
      primary imprint that marked the parental origin. Therefore, these mono
      chromosomal hybrids could provide a valuable in vitro system to study the
      mechanisms involved in the regulation of imprinted gene expression.

PMID- 9663660
TI  - BRAM1, a BMP receptor-associated molecule involved in BMP signalling.
AB  - BACKGROUND: TGF-beta superfamily members elicit signals through the stimulation
      of serine/threonine-kinase receptors. Recently, molecules associated with several
      TGF-beta family receptors have been cloned. One such molecule, the immunophilin
      FKBP12, has been reported to interact with TGF-beta family type I receptors.
      However, the identity of signalling specific molecules interacting with the
      receptor was unknown. RESULTS: To clarify the factors mediating bone
      morphogenetic protein (BMP) receptor signalling, a cytoplasmic molecule
      associated with the BMP type IA receptor (BMPR-IA) was isolated using the yeast
      two-hybrid system. We designated the molecule BMP receptor associated molecule 1
      (BRAM1). BRAM1 is an alternatively spliced form of BS69, a factor previously
      identified as an adenovirus E1A-associated protein. BRAM1 was localized to the
      cytoplasmic region in mammalian cells, whereas BS69 is localized to the nucleus.
      BRAM1 bound specifically to BMPR-IA in mammalian cells. The C-terminal half of
      BRAM1 was found to be sufficient for binding to BMPR-IA. CONCLUSIONS: BRAM1, a
      BMPR-IA associated molecule, was isolated using the yeast two-hybrid system, and
      found to associate specifically with BMPR-IA. BRAM1 may thus serve as an
      interacting protein in the BMP signal pathway.

PMID- 9663661
TI  - Squamous cell carcinoma of the tongue in young patients: a matched-pair analysis.
AB  - BACKGROUND: Tongue cancer is seen with increasing frequency in young individuals.
      There is controversy concerning the clinical course and outcome for oral tongue
      cancer in young patients. METHODS: A retrospective review of 36 patients under 40
      years of age with squamous cell carcinoma of the tongue was performed. These
      patients were matched to an older population. The 5-year disease-free survival;
      rates of local, regional, and distant failure; and rate of second primary tumor
      were determined for both populations. RESULTS: The 5-year disease-free survival
      for the young patients was 62% versus 69% in the older population (p = .30). Ten
      of 36 (28%) of younger patients recurred locally versus five of 36 (14%) of the
      older patients (p = .11). Nine of 36 (25%) younger patients recurred regionally
      in the younger group versus six of 36 (17%) patients in the older group (p =
      .25). Sixteen of 36 (44%) of the younger patients had locoregional failure versus
      eight of 36 (22%) of the older patients (p < .05). The rates of metastatic
      disease and second primary lesions were similar in both populations. CONCLUSIONS:
      In this series, younger patients with squamous cell carcinoma of the oral tongue
      had a higher rate of locoregional recurrence rate than did older patients. This
      did not translate into a survival difference.

PMID- 9663662
TI  - Carcinoma of the skin metastatic to the parotid area lymph nodes.
AB  - BACKGROUND: We performed an analysis of treatment outcome at the University of
      Florida for 77 patients with previously untreated carcinoma of the skin
      metastatic to parotid area lymph nodes. METHODS: Seventy-seven patients with 79
      parotid node metastases were treated with curative intent between 1966 and 1994.
      All patients had a minimum 2-year follow-up. Treatment consisted of radiotherapy
      alone in 18 patients, preoperative radiotherapy in 6 patients (7 parotids), and
      postoperative radiotherapy in 53 patients (54 parotids). RESULTS: Overall rate of
      disease control in the parotid area at 5 years was 82%. Parotid area disease
      control according to treatment group revealed: surgery and postoperative
      radiotherapy, 43 of 48 (90%); preoperative radiotherapy and surgery, 4 of 5
      (80%); and radiotherapy alone, 8 of 15 (53%). Multivariate analysis of parotid
      disease control revealed the following: treatment method (p = .0037), N stage (p
      = .0726), cranial nerve involvement (p = .1851), fixation (p = .1820), skin
      involvement (p = .1771), and sex (p = .5782). Overall 5-year absolute and cause
      specific survival rates were 54% and 68%, respectively. The 5-year cause-specific
      survival rate was 72% after surgery and postoperative radiotherapy and 59%
      following radiotherapy alone. Multivariate analysis of cause-specific survival
      revealed the following: skin involvement (p = .0215), cranial nerve involvement
      (p = .1549), fixation (p = .0347), N stage (p = .4302), sex (p = .6806), and
      treatment method (p = .9599). CONCLUSIONS: Our current policy is to treat
      patients with tumor that is initially resectable with surgery followed by
      radiotherapy, whereas those who have initially unresectable disease undergo
      preoperative radiotherapy followed by surgical resection if the tumor becomes
      resectable. If surgery cannot be performed for medical reasons, patients still
      have better than a 50% chance of being cured with radiotherapy alone.

PMID- 9663663
TI  - Carotid body tumors in inhabitants of altitudes higher than 2000 meters above sea
      level.
AB  - BACKGROUND: Carotid body tumors (CBTs) are rare. Diagnosis is usually delayed
      until the tumors reach a critical volume and a mass appears in the neck, which is
      often asymptomatic. METHODS: We reviewed retrospectively the cases with CBT
      diagnosed from 1965 to 1995 in the Hospital de Oncologia in Mexico City with
      inhabitants at an altitude higher than 2200 m above sea level to see whether
      these tumors have the same characteristics as those of inhabitants of countries
      of lower altitudes. We reviewed the clinical features, diagnostic procedures,
      therapy, results, and complications. RESULTS: There were 120 CBT cases, which
      represent 79% of the parapharyngeal space tumors diagnosed at our hospital; 116
      (96%) were benign and 4 (3.3%) were malignant. Women predominated (89%), and the
      female-male ratio was 8.3:1. Five patients had multiple paragangliomas, and one
      had a family history of CBT. Eighty patients (66%) underwent surgery. This was
      done by cervical approach in 78 cases (97%), and 2 (2.5%) required additional
      mandibulotomy. There were three deaths due to brain ischemia after carotid
      ligature. Forty-one patients were followed without treatment, due to advanced
      age, concomitant diseases, or great volume of the tumor. Median follow-up of
      these patients was 47 months, during which time no patient reported additional
      symptoms, accelerated enlargement of the tumor, or metastasis. With a median
      follow-up of 54 months, only one patient developed local recurrence and three
      patients developed distant metastasis. CONCLUSIONS: We conclude that cases of CBT
      in our high-altitude population differ significantly from those cases in
      inhabitants of cities in the U.S. or Europe of less than 1500 m above sea level.
      Those of high altitudes have an evident female predominance (8.3:1), low rate of
      bilaterality (5%), and a family history of 1% versus a discrete female
      predominance (2:1), bilaterality from 10% to 20%, and family history from 7% to
      25% in low altitudes. When adequate criteria are used to determine surgical
      resectability, a complete resection is achieved in 85% of cases, with low or null
      mortality and high local control.

PMID- 9663664
TI  - Results of accelerated radiotherapy for supraglottic carcinoma: a Massachusetts
      General Hospital and Massachusetts Eye and Ear Infirmary experience.
AB  - BACKGROUND: Carcinoma of the supraglottic larynx is a relatively common
      malignancy treated with either surgery, radiotherapy, or a combined approach.
      METHODS: The radiotherapy records of 190 patients with carcinoma of the
      supraglottic larynx treated at the Massachusetts General Hospital (MGH) and
      Massachusetts Eye and Ear Infirmary (MEEI) from 1981 to 1992 were reviewed. Of
      these patients, 164 were available for evaluation for local control and 169 for
      disease-specific survival. The patients were treated with accelerated
      hyperfractionated radiotherapy to 67.2-72 Gy/1.6 Gy per fraction twice a day in 6
      weeks. The median follow-up was 56 months. Five-year actuarial local and regional
      control, relapse-free and overall survival, and voice-preservation rates were
      analyzed. RESULTS: For T1, T2, T3, and T4 tumors, local control rates were 96%,
      86%, 76%, and 43%, respectively (p < .01), and the corresponding relapse-free
      survival rates were 78%, 82%, 64%, and 40% (p < .01). For the patients with N0,
      N1, and N2-3 disease, local control rates at the primary site were 86%, 74%, and
      46%, respectively (p < .01), and the corresponding relapse-free survival rates
      were 79%, 53%, and 39% (p < .01). Including surgical salvage, the ultimate local
      control rates were 96%, 93%, 88%, and 51%, respectively (p < .01). Voice
      preservation rate for the entire group was 79% and for T1, T2, T3, and T4 tumors,
      rates were 96%, 80%, 72%, and 43%, respectively. CONCLUSIONS: Our experience with
      accelerated hyperfractionated radiotherapy for supraglottic carcinoma showed
      excellent locoregional control, relapse-free survival, and laryngeal
      preservation. The radiation toxicity was acceptable. The T and N stages were
      significant predictors of outcome, and the T4 tumors and node-positive neck
      disease portended a poor prognosis and therefore should be considered for
      protocols that include adjuvant therapies.

PMID- 9663665
TI  - Phase II study of N-phosphonacetyl-L-aspartate, recombinant interferon-alpha, and
      fluorouracil infusion in advanced squamous cell carcinoma of the head and neck.
AB  - BACKGROUND: 5-Fluorouracil (5-FU), as a single agent, produces a 15% response
      rate in advanced squamous cell carcinoma of the head and neck (SCCHN). N
      phosphonacetyl-L-aspartate (PALA) inhibits pyrimidine biosynthesis and increases
      incorporation of 5-FU metabolites into ribonucleic acid (RNA). Recombinant alpha
      interferon-2b (rIFN-alpha-2b) may inhibit 5-FU clearance and blunt reflex rise in
      thymidylate synthetase, therefore enhancing inhibition of the target enzyme of 5
      FU. METHODS: In an attempt to exploit their potential therapeutic synergy, we
      initiated a phase II trial combining PALA 250 mg/m2 by intravenous (IV) bolus day
      1 with 5-FU 2600 mg/m2 24-hour IV infusion initiated 24 hours after PALA,
      followed by rIFNalpha-2b 10 million units (MU) by subcutaneous injection days 2,
      3, and 4 in patients with advanced, measurable SCCHN incurable with surgery or
      radiotherapy. Treatment was repeated weekly; patients were assessed every 4-6
      weeks. Pretreatment tumor specimens were analyzed for p53 mutations in exons 5-8
      and for protein expression using the p53 polyclonal antibody CM-1. RESULTS:
      Nineteen patients were enrolled from November 1991 through February 1994. Median
      age was 59 years (range, 31-72 years). All had previously received definitive
      radiotherapy, and all but two had undergone surgical resection. Seven patients
      (37%) had received prior adjuvant chemotherapy. Median time from initial
      diagnosis to protocol enrollment was 17 months (range, 5 months to 10 years).
      Median performance status (PS) was 1. Primary tumor sites included oral cavity (8
      patients), larynx (7 patients), oropharynx (3 patients), and hypopharynx (1
      patient). The median serum transferrin was 241 (range, 141-333). Sixteen patients
      (84%) had sufficient pretreatment biopsy material for p53 analysis. Patients
      received a median of 6 weeks of treatment (range, 2-30 weeks). Six patients (32%)
      in the absence of disease progression failed to finish the first 6 weeks of
      treatment: 3 died of pulmonary insufficiency or pneumonia and 3 were removed from
      study during the first 6 weeks due to toxicity. Grade 2-3 flulike symptoms
      occurred in 17 patients (89%); grade > or = 3 fatigue occurred in 12 patients
      (63%), and grade > or = 2 stomatitis occurred in 5 (26%). Gastrointestional
      toxicity was minimal and myelosuppression mild. Of 13 evaluable patients, there
      were 2 partial responses (15%) lasting 3 months and 20 months; 5 patients with
      stable disease lasting 2, 2, 2.5, 3, and 4.5 months; and 6 with disease
      progression. For all 19 patients, the overall response rate was 11%, the median
      survival was 6 months and 1-year survival rate 26%. Lower transferrin values (<
      or =241) were associated with shortened median survival 2.5 vs 11 months).
      Increased p53 protein expression but not p53 mutations in pretreatment specimens
      also predicted inferior survival (median, 6 vs 11 months) after enrollment in
      study (p = .0124). CONCLUSIONS: Biochemical modulation of 5-FU by rIFNalpha-2b
      and PALA does not enhance its efficacy in patients with advanced SCCHN whose
      disease has progressed after prior radiotherapy. Serum transferrin and p53
      protein expression segregate outcome in this group of uniformly treated patients.

PMID- 9663666
TI  - DNA ploidy, proliferative activities, and immunophenotype of malignant lymphoma:
      application of flow cytometry.
AB  - BACKGROUND: To explore the flow cytometric diagnosis of malignant lymphoma, we
      examined the deoxyribonucleic acid (DNA) ploidy, proliferative activities, and
      immunophenotype of surgical biopsy- and fine-needle aspiration (FNA)-derived
      materials. Our goal was to determine the possibility of making a diagnosis of
      malignant lymphoma by flow cytometric analysis of FNA-derived materials. METHODS:
      The DNA ploidy and proliferative indices including the percentage of S-phase
      fraction (SPF), G2 + M fraction (G2M), and Ki-67-positive fraction (Ki-67) were
      analyzed on the fresh materials from 84 consecutive patients with suspected
      malignant lymphoma. Flow cytometric analysis of surface antigens was
      simultaneously performed. Fourteen of the patients underwent FNA and subsequent
      surgical biopsy of the same lymph nodes for flow cytometric analysis. RESULTS:
      The proliferative indices of intermediate-grade non-Hodgkin's lymphomas (NHL) (n
      = 28) and high-grade NHL (n = 23) were significantly higher than those of the
      reactive hyperplasia (n = 25). The total for SPF + G2M of 6% was a satisfactory
      threshold for differentiating these NHL from reactive hyperplasia (sensitivity of
      84%, specificity of 88%, and accuracy of 86%). However, low-grade NHL (n = 3) and
      Hodgkin's lymphoma (HL, n = 5) could not be discriminated by employing this
      parameter. DNA aneuploidy was seen in 13 of the 28 intermediate-grade NHL and 8
      of the 23 high-grade NHL, whereas it was not seen in 25 reactive hyperplasia, 3
      low-grade NHL, and 5 HL. The percentage of CD19-positive cells in B-cell NHL or
      CD3-positive cells in T-cell NHL was significantly higher compared with those for
      reactive hyperplasia. The percentage of CD16 + CD56-positive cells in natural
      killer (NK) cell NHL was extremely high, with a mean of 91.8%. Flow cytometric
      results for FNA-derived materials showed excellent correlation with those for
      surgical biopsy-derived specimens. CONCLUSIONS: Analyses of DNA ploidy,
      proliferative activities, and immunophenotype by flow cytometry (FCM) are useful
      for diagnosing intermediate- and high-grade NHL. Fine-needle aspiration is a less
      invasive approach than surgical biopsy, and, when combined with FCM, it may have
      a place in the diagnosis of NHL.

PMID- 9663667
TI  - Risk factors for malignancy in adult tonsils.
AB  - BACKGROUND: Tonsillectomy in adults (age 18 years and older) is performed for a
      variety of conditions. The palatine tonsils may harbor carcinoma or lymphoma, and
      this potentially unanticipated finding may follow routine tonsillectomy in the
      adult. The ability to preoperatively identify adult tonsillectomy patients at
      increased risk for tonsillar malignancy could sensitize the clinician to this
      possibility and the potential need for expedited rather than routine
      tonsillectomy scheduling. METHODS: A retrospective review of 476 consecutive
      adult patients who underwent tonsillectomy during the last 10 years at the
      University of Iowa Hospitals and Clinics was undertaken. Proposed risk factors
      for tonsillar malignancy included a prior history of head and neck cancer,
      tonsillar asymmetry, palpable firmness or visible lesion in the tonsil, neck
      mass, unexplained weight loss, and unexplained constitutional symptoms. These
      risk factors were correlated with the pathologic diagnosis in the reviewed cases.
      RESULTS: Of these 476 patients, 25 had malignant tonsil pathology. No patient
      without risk factors was found to have malignancy on pathologic evaluation of the
      tonsils. Of the 25 patients with malignant tonsillar pathology, 23 had two or
      more risk factors, and 2 patients had one risk factor. Tonsillar asymmetry, found
      in 20 of the 25 cases, was the risk factor most frequently associated with
      malignant pathology. CONCLUSIONS: These results indicate that the presence of
      certain preoperatively identifiable risk factors are associated with the
      pathologic finding of malignancy in adult tonsillectomy specimens. Based on these
      criteria, a model which is predictive of the presence of tonsil malignancy may be
      constructed.

PMID- 9663668
TI  - Loss of heterozygosity on chromosome 2q: possibly a poor prognostic factor in
      head and neck cancer.
AB  - BACKGROUND: Loss of heterozygosity (LOH) correlates with inactivated tumor
      suppressor genes. The aim of this study was to see if LOH on chromosomes 2q, 3p,
      5q, 9p, and 17p correlated with survival in early squamous cell carcinoma of the
      head and neck (SCCHN). METHODS: A case control study was performed. Ten patients
      with stage I or II tumors who ultimately died of their disease were identified
      and matched with suitable controls. None of the controls had a local recurrence
      and at time of last follow-up were alive with no evidence of disease or had died
      of an unrelated illness. The deoxyribonucleic acid (DNA) was extracted from
      paraffin blocks, and LOH studies were performed using microsatellite markers.
      RESULTS: The respective incidence of allelic loss for the index and control
      patients was as follows: chromosome 2q, 75% and 20% (p = .03); chromosome 3p, 71%
      and 57%, respectively (not significant); chromosome arm 5q, 30% and 25% (not
      significant); chromosome arm 9p, 71% and 73% (not significant); and chromosome
      arm 17p, 75% and 46% (not significant). Therefore, loss on chromosome 2q strongly
      correlated with poor survival (odds ratio = 10.4). CONCLUSION: Loss of
      heterozygosity on chromosome 2q may correlate with a poor prognosis in early
      stage SCCHN.

PMID- 9663669
TI  - A modified protocol for early treatment of osteomyelitis and osteoradionecrosis
      of the mandible.
AB  - BACKGROUND: The treatment of osteoradionecrosis (ORN) and early chronic
      osteomyelitis (COM) of the mandible and maxilla is controversial. Hyperbaric
      oxygen (HBO) at two to three times the atmospheric pressure at sea level can
      result in tissue oxygen tension of almost 400 mmHg. Herewith HBO increases oxygen
      supply in hypoxic tissue, thus inducing fibroblastic proliferation and capillary
      formation. METHODS: From 1981 to 1991, we used a monoplace chamber and since
      1992, we have also had a multiplace chamber for HBO treatment. Hyperbaric oxygen
      was given at 2.5-2.8 atmosphere absolute pressure (ATA) for 90-120 minutes, once
      per day. The patients had five to 10 preoperative and five to seven postoperative
      sessions. Surgical therapy consisted of decortication of the affected bone,
      subsequently covered with a free periosteal transplant from the tibia. RESULTS:
      Thirty-six patients with ORN and 33 with COM of the mandible and maxilla was
      treated with this protocol. The median follow-up time in this material is 34
      months, with a minimum of 10 months. Thirty-six ORN patients (92%) and 26 COM
      patients (79%) have remained symptom-free after the first treatment period. Three
      failed ORN patients were successfully treated with a free microvascular flap. The
      seven failed COM patients have been retreated, and five of them have occasional
      clinical symptoms. CONCLUSIONS: Hyperbaric oxygen is a promising adjunct to
      surgery in the treatment of mandibular and maxillary ORN and COM. Using this
      protocol, the necessary HBO treatment sessions have been reduced from earlier
      protocols, without adverse effect on the outcome.

PMID- 9663670
TI  - Recurrent respiratory papillomatosis.

PMID- 9663671
TI  - Ventriculosaccular lymphoepithelioma of the larynx: case report and literature
      review.
AB  - BACKGROUND: Lymphoepithelioma is a very rare neoplasm of the larynx. The authors
      have reviewed the available published literature on the subject and found eight
      studies on lymphoepithelioma. Lymphoepitheliomas derive from the epithelial and
      lymphatic tissues of the laryngeal ventricule. The rarity of the occurrence of
      lymphoepithelioma makes it difficult to define its clinical features and general
      treatment methods. METHODS: The authors present a description of a
      lymphoepithelioma located in the left laryngeal sacculus, extending into the pre
      epiglottic space and infiltrating the epiglottis with an ulceration of its
      laryngeal surface. A total laryngectomy and a left radical neck dissection were
      performed. After surgery, radiotherapy treatment was applied to the left cervical
      and laryngeal areas. Two years after the initial radiotherapy, the patient died
      during palliative chemotherapy (for metastases). RESULTS: In patients with
      lymphoepithelioma of the larynx, the following can be observed: (1) bulging of
      the laryngeal ventricule, with or without ulceration of the laryngeal surface of
      the epiglottic mucosa; (2) early lymph node and remote matastases. CONCLUSIONS:
      In the early stages of lymphoepithelioma, radiotherapy is the method of choice.
      In advanced cases of lymphoepithelioma, radiotherapy supplements surgical
      treatment.

PMID- 9663672
TI  - Squamous cell carcinoma of the tongue associated with cinnamon gum use: a case
      report.
AB  - BACKGROUND: Cinnamon aldehydes found in cinnamon-flavored gums can incite mucosal
      alterations at points of contact with the oral mucosa. These alterations may
      include inflammation and epithelial proliferation, but as a rule, the changes are
      reversible and promptly resolve when gum-chewing activity is discontinued.
      METHODS: The authors report a case of a 24-year-old woman who developed a
      squamous cell carcinoma of the tongue following persistent and prolonged exposure
      to cinnamon-flavored gum. RESULTS: Several social, clinical, and histopathologic
      features point to the cinnamon-flavored chewing gum as a possible causal factor
      in the development of the patient's oral carcinoma. CONCLUSIONS: Prompt
      withdrawal of cinnamon products is encouraged in heavy gum chewers who develop
      cinnamon-related oral lesions. For those lesions which do not promptly resolve
      upon cinnamon withdrawal, diagnostic biopsy should be considered to exclude the
      possibility of a squamous cell carcinoma.

PMID- 9663673
TI  - Extending the supraomohyoid neck dissection in squamous cell carcinoma of the
      floor of mouth.

PMID- 9663674
TI  - PRD--a protein domain involved in PTS-dependent induction and carbon catabolite
      repression of catabolic operons in bacteria.
AB  - Several operon-specific transcriptional regulators, including antiterminators and
      activators, contain a duplicated conserved domain, the PTS regulation domain
      (PRD). These duplicated domains modify the activity of the transcriptional
      regulators both positively and negatively. PRD-containing regulators are very
      common in Gram-positive bacteria. In contrast, antiterminators controlling beta
      glucoside utilization are the only functionally characterized members of this
      family from gram-negative bacteria. PRD-containing regulators are controlled by
      PTS-dependent phosphorylation with different consequences: (i) In the absence of
      inducer, the phosphorylated EIIB component of the sugar permease donates its
      phosphate to a PRD, thereby inactivating the regulator. In the presence of the
      substrate, the regulator is dephosphorylated, and the phosphate is transferred to
      the sugar, resulting in induction of the operon. (ii) In gram-positive bacteria,
      a novel mechanism of carbon catabolite repression mediated by PRD-containing
      regulators has been demonstrated. In the absence of PTS substrates, the HPr
      protein is phosphorylated by enzyme I at His-15. This form of HPr can, in turn,
      phosphorylate PRD-containing regulators and stimulate their activity. In the
      presence of rapidly metabolizable carbon sources, ATP-dependent phosphorylation
      of HPr at Ser-46 by HPr kinase inhibits phosphorylation by enzyme I, and PRD
      containing regulators cannot, therefore, be stimulated and are inactive. All
      regulators of this family contain two copies of PRD, which are functionally
      specialized in either induction or catabolite repression.

PMID- 9663675
TI  - Nucleoside diphosphate kinase: role in bacterial growth, virulence, cell
      signalling and polysaccharide synthesis.
AB  - Nucleoside diphosphate kinase (Ndk) is an important enzyme that generates
      nucleoside triphosphates (NTPs) or their deoxy derivatives by terminal
      phosphotransfer from an NTP such as ATP or GTP to any nucleoside diphosphate or
      its deoxy derivative. As NTPs, particularly GTP, are important for cellular
      macromolecular synthesis and signalling mechanisms, Ndk plays an important role
      in bacterial growth, signal transduction and pathogenicity. Specific examples of
      the role of Ndk in regulating growth, NTP formation and cell surface
      polysaccharide synthesis in two respiratory tract pathogens, Pseudomonas
      aeruginosa and Mycobacterium tuberculosis, are discussed.

PMID- 9663676
TI  - Use of time-lapse microscopy to visualize rapid movement of the replication
      origin region of the chromosome during the cell cycle in Bacillus subtilis.
AB  - We describe the use of time-lapse fluorescence microscopy to visualize the
      movement of the DNA replication origin and terminus regions on the Bacillus
      subtilis chromosome during the course of the cell cycle. The origin and terminus
      regions were tagged with a cassette of tandem lac operator repeats and visualized
      through the use of a fusion of the green fluorescent protein to the LacI
      repressor. We have discovered that origin regions abruptly move apart towards the
      cell poles during a brief interval of the cell cycle. This movement was also seen
      in the absence of cell wall growth and in the absence of the product of the parB
      homologue spo0J. The origin regions moved apart an average distance of 1.4 microm
      in an 11 min period of abrupt movement, representing an average velocity of 0.17
      microm min(-1), and reaching a maximum velocity of greater than 0.27 microm min(
      1). The terminus region also exhibited a striking pattern of movement but not as
      far or a rapid as the origin region. These results provide evidence for a mitotic
      like motor that is responsible for segregation of the origin regions of the
      chromosomes.

PMID- 9663677
TI  - Replication at the telomeres of the Streptomyces linear plasmid pSLA2.
AB  - The Streptomyces linear plasmid pSLA2 initiates DNA replication bidirectionally
      towards its telomeres from a site located near the centre of the molecule; at the
      telomeres, the recessed ends of lagging strands are filled in by non-displacing
      DNA synthesis. Here, we report experiments that test three proposed mechanisms
      for lagging-strand fill-in. We present data inconsistent with recombinational or
      terminal hairpin models for the formation of full-length duplex pSLA2 DNA.
      Instead, we find that deletions in short, distantly separated homologous
      palindromes in the leading-strand 3' overhang prevent propagation of linear pSLA2
      DNA, implicating a mechanism of palindrome-mediated leading-strand fold-back in
      telomere replication. We further show that circularized pSLA2 DNA molecules are
      opened in vivo precisely at the terminal nucleotides of telomeres, generating
      functional linear replicons containing native telomeres covalently bound to a
      protein at their 5' DNA termini. Together, our results support a model in which
      pairing of multiple widely separated pSLA2 palindromes anchors the 3' end of the
      leading-strand overhang to a site near the overhang's base -- providing a
      recognition site for terminal-protein-primed DNA synthesis and subsequent
      endonucleolytic processing. Thus, the replication of Streptomyces plasmid
      telomeres may have features in common with the mechanism proposed for telomere
      replication in autonomous parvoviruses.

PMID- 9663678
TI  - The telomeres of Streptomyces chromosomes contain conserved palindromic sequences
      with potential to form complex secondary structures.
AB  - The chromosomes of the gram-positive soil bacteria Streptomyces are linear DNA
      molecules, usually of about 8Mb, containing a centrally located origin of
      replication and covalently bound terminal proteins (which are presumably involved
      in the completion of replication of the telomeres). The ends of the chromosomes
      contain inverted repeats of variable lengths. The terminal segments of five
      Streptomyces chromosomes and plasmids were cloned and sequenced. The sequences
      showed a high degree of conservation in the first 166-168bp. Beyond the terminal
      homology, the sequences diverged and did not generally cross-hybridize. The
      homologous regions contained seven palindromes with a few nucleotide differences.
      Many of these differences occur in complementary pairs, such that the
      palindromicity is preserved. Energy-optimized modelling predicted that the 3'
      strand of the terminal palindromes can form extensive hairpin structures that are
      similar to the 3' ends of autonomous parvovirus genomes. Most of the putative
      hairpins have a GCGCAGC sequence at the loop, with the potential to form a stable
      single C-residue loop closed by a sheared G:A pairing. The similarity between the
      terminal structures of the Streptomyces replicons and the autonomous parvoviral
      genomes suggests that they may share some structural and/or replication features.

PMID- 9663679
TI  - A newly identified regulator is required for virulence and toxin production in
      Pseudomonas syringae.
AB  - The genes lemA (which we here redesignate gacS) and gacA encode members of a
      widely conserved two-component regulatory system. In Pseudomonas syringae strain
      B728a, gacS and gacA are required for lesion formation on bean, as well as for
      the production of protease and the toxin syringomycin. A gene, designated salA,
      was discovered that restored syringomycin production to a gacS mutant when
      present on a multiple-copy plasmid. Disruption of chromosomal salA resulted in
      loss of syringomycin production and lesion formation in laboratory assays.
      Sequence analysis of salA suggests that it encodes a protein with a DNA-binding
      motif but without other significant similarity to proteins in current databases.
      Chromosomal reporter fusions revealed that gacS and gacA positively regulate
      salA, that salA upregulates its own expression and that salA positively regulates
      the expression of a syringomycin biosynthetic gene, syrB. Loss of syringomycin
      production does not account for the salA mutant's attenuated pathogenicity, as a
      syrB mutant was found to retain full virulence. The salA gene did not similarly
      suppress the protease deficient phenotype of gacS mutants, nor were salA mutants
      affected for protease production. A gacS/gacA-dependent homoserine lactone
      activity as detected by bioassay was also unaffected by the disruption of salA.
      Thus, salA appears to encode a novel regulator that activates the expression of
      at least two separate genetic subsets of the gacS/gacA regulon, one pathway
      leading to syringomycin production and the other resulting in plant disease.

PMID- 9663680
TI  - The Bacillus SpoIIGA protein is targeted to sites of spore septum formation in a
      SpoIIE-independent manner.
AB  - The process of bacterial cell division involves the assembly of a complex of
      proteins at the site of septation that probably provides both the structural and
      the cytokinetic functions required for elaboration and closure of the septal
      annulus. During sporulation in Bacillus subtilis, this complex of proteins is
      modified by the inclusion of a sporulation-specific protein, SpoIIE, which plays
      a direct role in gene regulation and also has a genetically separable role in
      determining the gross structural properties of the specialized sporulation
      septum. We demonstrate by both green fluorescent protein (GFP) fusions and
      indirect immunofluorescence microscopy that SpoIIGA, a protein required for
      proteolytic cleavage of pro-sigmaE, is also targeted to the sporulation septum.
      Septal localization of SpoIIGA-GFP occurred even in the structurally abnormal
      septum formed by a SpoIIE null mutant. We also report the isolation of a spoIIGA
      homologue from Bacillus megaterium, a species in which the cells are
      significantly larger than those of B. subtilis. We have exploited the physical
      dimensions of the B. megaterium sporangium, in conjunction with wide-field
      deconvolution microscopy, to construct three-dimensional projections of
      sporulating cells. These projections indicate that SpoIIGA-GFP is initially
      localized in an annulus at the septal periphery and is only later localized
      uniformly throughout the septa. Localization was also detected in a B. subtilis
      spo0H null strain that fails to construct a spore septum. We propose that SpoIIGA
      is sequestered in the septum by an interaction with components of the septation
      machinery and that this interaction begins before the construction of the
      asymmetric septum.

PMID- 9663681
TI  - The BvgAS virulence control system regulates type III secretion in Bordetella
      bronchiseptica.
AB  - The BvgAS signal transduction system in Bordetella spp. mediates a transition
      between infectious (Bvg+) and non-infectious (Bvg-) phases by sensing
      environmental conditions and regulating gene expression. Using differential
      display, arbitrary-primed polymerase chain reaction (PCR), we identified a gene
      expressed in the Bvg+ phase of Bordetella bronchiseptica that shows a high degree
      of sequence similarity to a locus involved in providing energy for type III
      secretion in pathogenic gram-negative bacteria (yscN in Yersinia spp.). We
      determined that the expression of this homologue in B. bronchiseptica (designated
      bscN) is regulated by bvg. Several open reading frames surrounding the bscN locus
      also show sequence similarity to loci encoding type III secretion apparatus
      components in other bacteria. An in-frame deletion of bscN in B. bronchiseptica
      leads to decreased secretion of several proteins, decreased cytotoxicity towards
      cultured cell lines and a defect in causing tyrosine dephosphorylation of
      specific proteins in infected cells in vitro. The deletion strain also revealed
      that bscN-mediated secretion is required for persistent colonization of the
      trachea in a rat infection model. Loci encoding type III secretion homologues
      were identified in four strains of B. pertussis and two strains of B.
      parapertussis. B. pertussis strain 18323 and an ovine isolate of B. parapertussis
      show significant transcription of the genes in vitro.

PMID- 9663682
TI  - The rpfA gene of Xanthomonas campestris pathovar campestris, which is involved in
      the regulation of pathogenicity factor production, encodes an aconitase.
AB  - Xanthomonas campestris pv campestris (Xcc) is a plant pathogenic bacterium that
      controls the production of pathogenicity factors in part by a cluster of genes
      designated rpf (regulation of pathogenicity factors). Sequence analysis of one of
      these genes (rpfA) revealed an open reading frame with amino acid sequence
      similarity to aconitases from other bacteria. Aconitase activity was lower in
      cellular extracts of an rpfA::Tn5 mutant than in those from the wild type. A
      zymogram of aconitase activity after native gel electrophoresis showed the
      presence of two distinct aconitases in Xcc; the major aconitase was absent in the
      rpfA::Tn5 mutant. This mutant also had reduced levels of extracellular enzymes
      and extracellular polysaccharide (EPS). Supplying rpfA in trans to the rpfA::Tn5
      mutant restored both the major aconitase activity and the synthesis of these
      pathogenicity factors. The transcription of the genes for two extracellular
      enzymes (prtA, encoding a serine protease, and engXCA, encoding endoglucanase)
      was reduced in the rpfA mutant background. Because some eukaryotic aconitases are
      also involved in iron regulation, we explored a possible connection between rpfA
      and iron metabolism. Intracellular iron levels in the mutants were lower than in
      the wild type as assessed by sensitivity to the iron-activated antibiotic,
      streptonigrin. Wild-type bacteria grown in iron-deficient conditions had a
      similar sensitivity to streptonigrin as the aconitase mutant. Overall, these
      results suggest that a prokaryotic aconitase can also act as a regulator of gene
      expression and that the regulation is possibly related to changes in
      intracellular iron levels.

PMID- 9663683
TI  - Interplay between global regulators of Escherichia coli: effect of RpoS, Lrp and
      H-NS on transcription of the gene osmC.
AB  - The transcription of the osmC gene of Escherichia coli is regulated as a function
      of the phase of growth. It is induced during the decelerating phase, before entry
      into stationary phase. osmC expression is directed by two overlapping promoters,
      osmCp1 and osmCp2. osmCp2 is mainly transcribed by E-sigma(s), the RNA polymerase
      using the sigma(s) (RpoS) sigma factor, and is responsible for the growth phase
      regulation. Transcription from osmCp1 is independent of sigma(s). The leucine
      responsive protein (Lrp) has been shown to bind the osmC promoter region in band
      shift experiments. In vivo analysis using osmC-lacZ transcriptional fusions
      demonstrated that Lrp affects the expression of both promoters. It represses the
      transcription of osmCp1 and activates the transcription of osmCp2 by E-sigma(s).
      An absence of Lrp results in an increase in the amount of RpoS during exponential
      growth in minimal medium. The nucleoid-associated protein H-NS also represses
      osmC transcription from both promoters. However, this happens through different
      mechanisms. The effect on osmCp2 is probably mediated by the increase in sigma(s)
      concentration in the cytoplasm of hns- mutants, while the effect on osmCp1 is
      independent of sigma(s). No binding of H-NS to the promoter region DNA could be
      detected, indicating that the effect on osmCp1 could also be indirect.

PMID- 9663684
TI  - A fixed distance for separation of newly replicated copies of oriC in Bacillus
      subtilis: implications for co-ordination of chromosome segregation and cell
      division.
AB  - The Spo0J protein of Bacillus subtilis is required for normal chromosome
      segregation and forms discrete subcellular assemblies closely associated with the
      oriC region of the chromosome. Here we show that duplication of Spo0J foci occurs
      early in the DNA replication cycle and that this requires the initiation of DNA
      replication at oriC but not elongation beyond the nearby STer sites. Soon after
      duplication, sister oriC/Spo0J foci move rapidly apart to achieve a fixed
      separation of about 0.7 microm, reminiscent of the segregation of eukaryotic
      chromosomes on the mitotic spindle. The magnitude of the fixed separation
      distance may explain how chromosome segregation is kept in close register with
      cell growth and the initiation mass for DNA replication. It could also explain
      how segregation can proceed accurately in the absence of cell division. The
      kinetics of focal separation suggest that one role of Spo0J protein may be to
      facilitate formation of separate sister oriC complexes that can be segregated.

PMID- 9663685
TI  - Identification of the Rhodobacter sphaeroides SOS box.
AB  - Gel-mobility shift assays with crude cell extracts of Rhodobacter sphaeroides,
      which belongs to the alpha group of the proteobacteria, have shown that a protein
      binds to the promoter of its recA gene, resulting in two retardation bands.
      Analysis of the minimal region of the R. sphaeroides recA gene required for the
      formation of the DNA-protein complexes, revealed the presence of the motifs
      GTTCN7GATC and GAACN7GAAC, which are centred at positions -21 and +8 from the
      transcriptional starting point respectively. Using PCR mutagenesis, we have
      demonstrated that these two motifs are required for the formation of both DNA
      protein complexes in vitro as well as for the DNA damage-mediated inducibility of
      the recA gene in vivo. Furthermore, the level of the recA gene expression in the
      constitutive mutants is the same as that achieved by the wild-type cells after
      DNA damage, indicating that the binding protein must be a repressor. The motif
      GTTCN7GTTC is also present upstream of the R. sphaeroides uvrA promoter, which in
      vitro specifically binds to a protein and whose expression is DNA damage
      inducible. Mutagenesis of this motif abolishes both the binding of this protein
      to the uvrA promoter and the DNA damage-mediated expression of this gene. The
      fact that the recA and uvrA wild-type promoters compete with each other for the
      retardation band formation, but not with their mutant derivatives in any of these
      motifs, indicates that the same repressor binds to the operator of both genes.
      All these results lead us to propose the sequence GTTCN7GTTC as the SOS box of R.
      sphaeroides. This is the first SOS box known whose sequence is a direct repeat
      and not a palindrome.

PMID- 9663686
TI  - In vivo relations between pAMbeta1-encoded type I topoisomerase and plasmid
      replication.
AB  - A number of large extrachromosomal elements encode prokaryotic type I
      topoisomerases of unknown functions. Here, we analysed the topoisomerase Topbeta
      encoded by the Gram-positive broad-host-range plasmid pAMbeta1. We show that this
      enzyme possesses the DNA relaxation activity of type I topoisomerases.
      Interestingly, it is active only on plasmids that use DNA polymerase I to
      initiate replication, such as pAMbeta1, and depends on the activity of this
      polymerase. This is the first example, to our knowledge, of prokaryotic type I
      topoisomerase that is specific for a given type of replicon. During pAMbeta1
      replication in Bacillus subtilis cells, Topbeta promotes premature arrest of DNA
      polymerase I, approximately 190bp downstream of the replication initiation point.
      We propose that Topbeta acts on the early replication intermediates of pAMbeta1,
      which contain D-loops formed by DNA polymerase I-mediated strand displacement.
      The possible role of the resulting DNA Pol I arrest in plasmid replication is
      discussed.

PMID- 9663687
TI  - Tandem genes of Chlamydia psittaci that encode proteins localized to the
      inclusion membrane.
AB  - Chlamydiae are obligate intracellular bacteria that replicate within a non
      acidified vacuole, termed an inclusion. To identify chlamydial proteins that are
      unique to the intracellular phase of the life cycle, a lambda expression library
      of Chlamydia psittaci DNA was differentially screened with convalescent antisera
      from infected guinea pigs and antisera directed at formalin-fixed purified
      chlamydial elementary bodies (EBs). One library clone was identified that
      harboured two open reading frames (ORFs) with coding potential for similar-sized
      proteins of approximately 20 kDa. These proteins were subsequently termed IncB
      and IncC. Sequencing of the cloned insert revealed a strong Escherichia coli-like
      promoter sequence immediately upstream of incB and a 36nt intergenic region
      between the ORFs. Sequence analysis of the region upstream of incB and incC
      revealed two ORFs that had strong homologies to an amino acid transporter and a
      sodium-dependent transporter. Immunoblotting with antisera directed at IncB or
      IncC demonstrated that these proteins are present in C. psittaci-infected HeLa
      cells but are absent or below the level of detection in purified EBs. Reverse
      transcriptase-polymerase chain reactions provided evidence that incB and incC are
      transcribed in an operon. Immunofluorescence microscopy demonstrated that IncB
      and IncC are each localized to the inclusion membrane of infected cells. No
      primary sequence similarity is evident between IncA, IncB or IncC, but each
      contains a large hydrophobic domain of similar size and character as in IncA.
      Analysis of the recently completed C. trachomatis serovar D genome database has
      revealed C. trachomatis ORFs encoding homologues to incB and incC, indicating
      that these genes are conserved among the chlamydiae.

PMID- 9663688
TI  - Natural competence for DNA transformation in Helicobacter pylori: identification
      and genetic characterization of the comB locus.
AB  - The gram-negative bacterial pathogen Helicobacter pylori, an important
      aetiological agent of gastroduodenal disease in humans, belongs to a group of
      bacterial species displaying competence for genetic transformation. Here, we
      describe the comB gene locus of H. pylori involved in DNA transformation
      competence. It consists of a cluster of four tandemly arranged genes with
      partially overlapping open reading frames, orf2, comB1, comB2 and comB3,
      constituting a single transcriptional unit. Orf2 encodes a 37-amino-acid peptide
      carrying a signal sequence, whereas comB1, comB2 and comB3 produce 29 kDa, 38 kDa
      and 42 kDa proteins, respectively, as demonstrated by immunoblotting with
      specific antisera. For Orf2 and ComB1, no homologous proteins were identified in
      the database. For ComB3, the best homologies were found with TraS/TraB from the
      Pseudomonas aeruginosa conjugative plasmid RP1 and TrbI of plasmid RP4, VirB10
      from the Ti plasmid of Agrobacterium tumefaciens and PtlG, a protein involved in
      secretion of pertussis toxin of Bordetella pertussis. Defined transposon knock
      out mutants in individual comB genes resulted in transformation-defective
      phenotypes ranging from a 90% reduction to a complete loss of the natural
      transformation efficiency. The comB2 and comB3 genes show homology to HP0528 and
      HP0527, respectively, located on the cagII pathogenicity island of H. pylori
      strain 26695.

PMID- 9663689
TI  - Phage-encoded genes and Salmonella virulence.

PMID- 9663690
TI  - Venoms, antivenoms and immunotherapy.
AB  - A century after the discovery of antivenom and despite real progress undertaken
      in its manufacture, its use remains largely empirical. Recent studies of
      pharmacokinetics of envenoming permitted improved understanding of immunotherapy.
      Improved purification of the antivenom by using immunoglobulin fragments has lead
      to increased tolerance and efficiency of antivenom. The respective advantages and
      disadvantages of F(ab')2 and F(ab) are discussed in relation to neutralising
      efficacy and clearance from the circulation. Although the time during which the
      action of antivenom remains beneficial after the bite is unknown, the superiority
      of intravenous administration has now been proved. Although immunisation
      procedures and purification and use of IgG fragments can be improved using modern
      technology, the future of immunotherapy seems promising. It is vital that
      therapeutic protocols should be rigidly adhered to in order to optimise
      immunotherapy. The use of vaccination has yet to be explored.

PMID- 9663691
TI  - The natriuretic peptide (ovCNP-39) from platypus (Ornithorhynchus anatinus) venom
      relaxes the isolated rat uterus and promotes oedema and mast cell histamine
      release.
AB  - In this study we characterise the ability of a C-type natriuretic peptide from
      platypus (Ornithorhynchus anatinus) venom (ovCNP-39) to relax the rat uterus in
      vitro and we investigate the possibility that ovCNP-39 contributes to the acute
      effects of envenomation, which include oedema, pain and erythema. We have found
      that both ovCNP-39 and the endogenous C-type natriuretic peptide, CNP-22, produce
      oedema in the rat paw and release histamine from rat peritoneal mast cells. Two
      synthetic peptides, ovCNP-39(1-17) and ovCNP-39(18-39), corresponding to the N-
      and C-termini, respectively, are equipotent histamine releasers, suggesting that
      ovCNP-39 and other natriuretic peptides do not act through conventional
      natriuretic peptide receptors on mast cells.

PMID- 9663692
TI  - Purification of a toxic factor from Arabian Gulf catfish epidermal secretions.
AB  - The Arabian Gulf catfish, Arius bilineatus (Valenciennes) secretes a
      proteinaceous epidermal secretion when threatened or injured. A toxic factor has
      been isolated and purified from the crude extract (crude skin toxin) of these
      secretions by a combination of gel filtration on Sephacryl S-300 and preparative
      discontinuous polyacrylamide gel electrophoresis. The purified skin toxin has a
      molecular weight of 39,000 Da and an isoelectric point (pI) of 5.45. Injection of
      the purified skin toxin into rabbits i.v. and determination of the LD50 indicated
      that the protein had been purified approximately 30 fold by these procedures.
      Injection of the purified skin toxin into rabbits caused agitation, convulsions
      and death within 5 min. Analysis of plasma levels of lactate dehydrogenase,
      glutamate-oxaloacetate transaminase and glutamate pyruvate transaminase in
      injected rabbits indicated that the skin toxin caused cardiac and liver damage to
      the animals.

PMID- 9663693
TI  - Preliminary evaluation of Vipera palaestinae snake bite treatment in accordance
      to the severity of the clinical syndrome.
AB  - The intravenous administration of a 60 ml dose of Vipera palaestinae antivenin
      was the suggested standard treatment of every bitten patient. In this study 85
      Vipera palaestinae bitten patients where selectively treated with antivenin
      depending on the severity of the clinical picture. Patients who developed
      systemic or severe local signs received 20 ml of antivenin over 30 min. If
      symptoms were still present, an additional 10 ml of antivenin was given until
      systemic signs subsided. Repeated doses of 10 ml of antivenin was administered in
      each case of systemic symptom relapse. 49% of patients did not exhibit any
      systemic symptoms and did not receive antivenin treatment. In 63% of antivenin
      treated cases symptoms were aborted by a single dose of 20 ml of antivenin. 23%
      of the antivenin treated patients needed 30-40 ml, 19 needed 50-60 ml and only 1
      patient (2%) received 80 ml of drug. Serum sickness complications were found in
      44% of antivenin treated patients. The results of this study show that antivenin
      treatment based on systemic symptoms is effective, required less antivenin than
      the treatment with fixed dose for each patient and reduces the incidence of serum
      sickness.

PMID- 9663694
TI  - Structure of a snake venom phospholipase A2 modified by p-bromo-phenacyl-bromide.
AB  - The crystal structure of acidic phospholipase A2 (APLA2) from Agkistrodon halys
      pallas covalently modified by p-bromo-phenacyl-bromide (pBPB) was determined to a
      resolution of 2.0 A by an isomorphous difference Fourier method with the native
      APLA2 structure as an initial model and refined to a crystallographic R factor of
      15.3%. The modified APLA2 structure is remarkably similar to that of the native
      one. Least-squares superposition of C alpha atoms of native and modified APLA2
      results in a root-mean-square coordinate deviation of 0.243 A. The p-bromo
      phenacyl group near the active site occupies a position similar to that in pBPB
      modified bovine pancreatic PLA2. The inhibitor covalently bound to the NDI atom
      of His48 fits well in the hydrophobic channel, forming extensive hydrophobic
      interactions with the surrounding residues, especially with the side chains of
      Phe5 and Cys45 and the main chain of Gly30. However, the inhibitor does not
      change the conformation of these residues except that Trp31 at the entrance of
      the hydrophobic channel moves slightly toward the inhibitor. Compared with native
      APLA2, the Ca2+-binding loop shows a little conformational change and a cation,
      probably Na+, occupies in the position of Ca2+. The binding of pBPB to APLA2
      induce no other significant conformational changes in the enzyme molecule
      elsewhere.

PMID- 9663695
TI  - Development of an ELISA for the detection of scorpion venoms in sera of humans
      envenomed by Androctonus australis garzonii (Aag) and Buthus occitanus tunetanus
      (Bot): correlation with clinical severity of envenoming in Tunisia.
AB  - A sandwich ELISA was set up for measuring scorpion venom levels in sera of
      accidentally envenomed humans with the aim to establish a quantitative
      relationship between these levels, envenoming severity and clinical symptoms.
      This assay used equine polyclonal F(ab')2, specific to two North African scorpion
      (Androctonus australis garzonii: Aag and Buthus occitanus tunetanus: Bot) venoms.
      The test proved to be simple, reproducible, very sensitive (detection limit = 0.9
      ng/ml) and linear between 0.5 and 15 ng/ml of venom concentrations. A large
      survey on scorpion sting envenomings was conducted from 1993 to 1996 in Tunisia
      to gather accurate epidemiological, clinical and biological data from victims as
      well as informations on the treatment that they had received. Victims were
      classified into three grades (GI, GII and GIII) of increasing severity according
      to clinical signs of envenoming. Blood samples were collected from victims and
      tested by ELISA for their content of Aag and Bot venoms. A strong correlation was
      found between clinical symptoms of envenoming and the level of scorpion venom
      antigens in serum (r = 0.980). Mean serum venom concentrations were: 2.65 +/-
      0.81 ng/ml in GI envenoming, 9.79 +/- 4.08 ng/ml in GII and 21.7 +/- 6.51 ng/ml
      in GIII. The difference between each group was statistically significant (p <
      0.01). This ELISA may prove to be helpful to establish a rationale approach of
      specific antivenom therapy.

PMID- 9663696
TI  - Mitochondrial swelling and oxygen consumption during respiratory state 4 induced
      by phospholipase A2 isoforms isolated from the South American rattlesnake
      (Crotalus durissus terrificus) venom.
AB  - The non-covalent interaction between two molecular entities namely, phospholipase
      A2 and crotapotin, results in the main toxin, crotoxin, present in the venom of
      the South American rattlesnake Crotalus durissus terrificus. High performance
      liquid chromatography has enabled us the isolation of three phospholipase A2
      isoforms (F1, F2 and F3), characterized through denaturing and non-denaturing
      polyacrylamide gel electrophoresis and also through the N-terminal amino acid
      sequence analysis. The effect of each purified phospholipase A2 isoform on
      isolated rat liver mitochondria was determined through mitochondrial swelling and
      O2 consumption during respiratory state 4. F1 showed a dose-dependent stimulation
      of O2 consumption while F2 and F3 caused stimulation only at low doses and
      inhibition at high amounts. These effects were completely suppressed by the
      presence of 0.1% bovine serum albumin or 0.5 mM EGTA in the incubation medium.
      Taking the mitochondrial swelling as an activity parameter, all of them presented
      the same behaviour at different intensities, leading to permeabilization of the
      mitochondrial membrane. In this case, addition of EGTA prevented it whereas
      bovine serum albumin was ineffective, indicating that the lipid microenvironment
      was affected. These results suggest that free fatty acids are directly
      responsible for the observed effects induced by phospholipase A2 isoforms on
      oxygen consumption experiments. The protection conferred by cyclosporin-A on
      swelling induced by the isoforms, when present in low concentrations, may suggest
      that cyclosporin-A binds to a mitochondrial membrane site protecting the membrane
      against the phospholipase A2 attack.

PMID- 9663697
TI  - Retrotransposable CR1-like elements in crotalinae snake genomes.
AB  - A part of the 3'-flanking region of BP-II gene, which is one of Trimeresurus
      flavoviridis venom gland phospholopase A2 (PLA2) isozyme genes, has a region
      homologous to avian chicken repeat 1 (CR1)-element. In the present study, ten CR1
      like elements were further identified in T. gramineus venom gland PLA2 isozyme
      genes, T. flavoviridis PLA2 inhibitor (PLI) genes, and T. flavoviridis and T.
      gramineus TATA-box binding protein (TBP) genes. Southern blot analysis using a
      probe for CR1 showed that Crotalinae snake genomes contain a number of CR1-like
      elements.

PMID- 9663698
TI  - Purification and characterization of three acidic, cytotoxic phospholipases A2
      from Indian cobra (Naja naja naja) venom.
AB  - Three acidic phospholipases A2 (NN-I2c-PLA2, NN-I2d-PLA2 and NN-I2c-PLA2) were
      purified by successive chromatography of Indian cobra (Naja naja naja) venom on
      CM-Sephadex C-25, Sephadex G-50 and QAE Sephadex A-25 columns. They have
      molecular weights of 13,000-14,500 by sodium dodecyl sulphate polyacrylamide gel
      electrophoresis. They showed tryptophan specific fluorescence emission spectra
      (approximately 345 nm). All the three phospholipases A2 were enzymatically highly
      active with specific activities 9-17 micromol min(-1) mg(-1). They were non
      lethal to mice when injected intraperitoneally in doses up to 10 mg kg(-1) body
      weight. They induced edema in mouse foot pads and were cytotoxic to Ehrlich
      ascites tumour cells. They did not exhibit direct haemolytic and anticoagulant
      activities.

PMID- 9663699
TI  - In vitro evaluation of the cytotoxic, hemolytic and clastogenic activities of
      Rhizostoma pulmo toxin(s).
AB  - Cytotoxic, hemolytic and clastogenic activities of Rhizostoma pulmo toxin(s)
      contained in the jelly tissue free of nematocysts were investigated in mammalian
      cells with in vitro procedures. At the concentration of 37.6 microg/ml the tissue
      protein produced the death of 50% V79 cells; a similar potency was observed in
      terms of hemolytic activity. The toxin(s) was not clastogenic for human
      lymphocytes in culture at the concentration of 5 microg/ml.

PMID- 9663700
TI  - Anticholinesterase activity of the fluorescent zoanthid pigment,
      parazoanthoxanthin A.
AB  - A synthetic linear tetrazacyclopent(f)azulene compound, parazoanthoxanthin A
      (m.w. 214.2), strongly fluorescent pigment occurring in zoanthids, was
      characterized and assayed for anticholinesterase activity. The pigment, emitting
      fluorescence at lambda(em) 420 nm, was found to be a pure competitive inhibitor
      of cholinesterases. At pH 8.0, a Ki value of 19 and 26 microM was determined with
      insect recombinant, and electric eel acetylcholinesterase. Horse serum
      butyrylcholinesterase was less sensitive with a Ki of 70 microM.

PMID- 9663701
TI  - Reduction of crotoxin-induced neuromuscular blockade by gamma radiation.
AB  - A comparative study between crotoxin and gamma irradiated crotoxin was performed
      on the indirectly evoked twitches and tetani of sciatic nerve-extensor digitorum
      longus muscle of rats. Crotoxin (3 to 14 microg/ml) decreased the amplitude of
      twitches and induced a slight tetanic fade, and irradiated crotoxin did not
      significantly affect either twitch amplitude or tetanic tension. Since gamma
      radiation reduced the neurotoxicity of crotoxin it may be useful for the
      production of anticrotalic serum.

PMID- 9663702
TI  - Bibliography of toxinology.

PMID- 9663703
TI  - Fibrinolytic agents inhibit platelet adhesion onto collagen type I-coated
      surfaces at high blood flow conditions.
AB  - The effect of fibrinolytic agents on platelet adhesion onto insolubilized
      collagen type I was evaluated. Normal human whole blood samples were incubated
      with agents and perfused over collagen-coated surfaces in a parallel-plate flow
      chamber. Platelet adhesion and aggregation were analyzed by video microscopy and
      image processing. When blood was perfused at 1500/s, both streptokinase and
      urokinase, each at 500 U/ml, caused a significantly less normalized platelet
      deposition, compared with controls. At 480/s, platelet deposition was not
      different between controls and test samples. Inhibition of platelet deposition at
      high flow rates was partly due to inhibition of platelet adhesion. Both
      ristocetin- and ADP-induced platelet aggregation were inhibited in test samples.
      The agents caused proteolytic degradation of plasma fibrinogen, but no
      degradation of platelet glycoproteins Ib and IIb-IIIa (GPIb and GPIIb-IIIa) and
      of plasma von Willebrand factor in test samples prior to perfusion. Post
      perfusion von Willebrand factor degradation was not found. Plasmin may cause
      functional changes to plasma proteins and/or platelet receptors, altering their
      adhesive properties under flow. At high shear, fibrinogen degradation products
      may interfere with GPIIb-IIIa binding to insolubilized von Willebrand factor,
      leading to decreased platelet adhesion. Inhibition of platelet adhesion by
      thrombolytic agents could help maintain vessel patency after recanalization in
      stenosed arteries. Publishers.

PMID- 9663704
TI  - Reconstituted recombinant factor VIII can be safely infused continuously for at
      least three days: it is a poor microbial growth medium.
AB  - Reconstituted recombinant factor VIII (FVIIIrec) loses little biologic activity
      at room temperature for up to seven days and continuous infusion is convenient,
      effective hemostatically and requires less FVIIIrec concentrate than treatment by
      conventional bolus injections. However, the potential for bacterial
      contamination, with proliferation to high levels that can cause bacteremia, is a
      concern with continuous infusion. We studied the growth properties at 4, 25 and
      35 degrees C in reconstituted FVIIIrec (Kogenate) and at 25 degrees C in 5%
      dextrose in water (D5%W) of three isolates each of Staphylococcus epidermidis,
      Staphylococcus aureus, Enterobacter cloacae, Klebsiella oxytoca, Serratia
      marcescens, Acinetobacter calcoaceticus, Stenotrophomonas maltophilia,
      Pseudomonas aeruginosa, Burkholderia cepacia, Flavobacterium spp. and Candida
      albicans, species most likely to contaminate infusate during preparation or
      administration and which have been implicated in more than 95% of all outbreaks
      and sporadic cases of nosocomial bloodstream infection traced to contaminated
      admixtures, biologic agents or medications administered parenterally.
      Reconstituted FVIIIrec allowed growth of only three species at 25 degrees C and
      35 degrees C: S. marcescens, S. maltophilia and P. aeruginosa; logarithmic growth
      appeared only after 24-48 h. D5%W allowed growth of two gram-negative species, S.
      marcescens and B. cepacia. We conclude that reconstituted FVIIIrec (Kogenate) is
      a poor growth medium for most nosocomial pathogens, comparable with D5%W. If
      reconstituted aseptically, continuous infusion of reconstituted FVIIIrec should
      be safe, and it should not be necessary to replace the container or tubing more
      frequently than every 3 days, an administration schedule that can provide
      effective hemostasis at lower cost.

PMID- 9663705
TI  - Involvement of platelet-derived 5-hydroxytryptamine in thromboxane A2-induced
      aggregation in cat platelets.
AB  - The present study was undertaken to examine the involvement of platelet-derived
      serotonin (5-hydroxytryptamine; 5-HT) in thromboxane A2 (TXA2)-induced platelet
      aggregation. Pharmacological experiments with 5-HT2 and TXA2 inhibitors were
      conducted on platelet aggregation in platelet-rich plasma from cats. Exogenously
      added 5-HT, U-46619 (a stable TXA2 analogue) and collagen caused platelet
      aggregation in a concentration-dependent manner. The combination of low
      concentrations of 5-HT and U-46619 caused full platelet aggregation, whereas each
      agent alone, at these concentrations, caused a transient aggregation. 5-HT
      induced aggregation was inhibited by ketanserin (0.01-0.3 micromol/l), a 5-HT2
      receptor antagonist, in a concentration-dependent manner. Collagen-induced
      platelet aggregation was also inhibited by ketanserin, whereas the inhibition by
      indomethacin was modest even at the highest concentration tested (300
      micromol/l). U-46619 triggered platelet aggregation in a biphasic manner.
      Ketanserin inhibited only the second phase of the aggregation. The inhibition of
      U-46619-induced aggregation by ketanserin occurred at a concentration range
      similar to that for 5-HT-induced platelet aggregation. Likewise, platelet
      aggregation induced by the combination of low concentrations of 5-HT and U-46619
      was fully inhibited by ketanserin. These data suggest a major involvement of
      platelet-derived 5-HT in TXA2-dependent aggregation in cat platelets.

PMID- 9663706
TI  - Cleavage of rhamnose from ristocetin A removes its ability to induce platelet
      aggregation.
AB  - Ristocetin A is used clinically as a tool for the measurement of von Willebrand
      protein due to its ability to induce the aggregation of platelets in plasma being
      proportional to the concentration of von Willebrand protein. The enzymatically
      induced cleavage of alpha-L-rhamnose from the tetrasaccharide of ristocetin A
      removes this ability to induce platelet aggregation in plasma, providing a
      possible insight into the structural basis for this effect.

PMID- 9663707
TI  - Impairment of plasma fibrinolysis in young survivors of myocardial infarction
      with silent ischaemia.
AB  - The aim of this study was to compare fibrinolytic parameters in two subgroups of
      young survivors of myocardial infarction: group A (n = 14) with silent myocardial
      ischaemia and group B (n = 15) without silent myocardial ischaemia, as assessed
      by 24 h Holter electrocardiogram monitoring. Only men aged 33-46 years who were
      in a stable condition at least 6 months after the acute event were included in
      the survey. All patients were normolipaemic or had only mild hyperlipidaemia, non
      diabetic, normotensive, non-current smokers and with a normal body mass index.
      The control group consisted of 15 age-matched healthy men. Blood samples were
      taken at 7.30 a.m. In the group A patients, we found higher mean levels of tissue
      plasminogen activator (t-PA) total antigen (11.1 versus 6.9 ng/ml, P < 0.01), its
      inhibitor plasminogen activator inhibitor-1 (PAI-1) antigen (58.1 versus 34.8
      ng/ml, P < 0.01), PAI-1 activity (4.9 versus 3.4 U/ml, P < 0.05) and tPA-PAI-1
      complexes (5.1 versus 3.5 ng/ml, P < 0.05) as well as a lower level of t-PA
      activity (0.5 versus 0.8 IU/ml, P < 0.01) and free t-PA antigen (0.8 versus 1.3
      ng/ml, P < 0.01) compared with the controls. However, group A patients exhibited
      higher PAI-1 antigen levels (58.1 versus 41.6 ng/ml, P < 0.05) than those without
      silent ischaemia. There were no differences between group B and controls in any
      of the parameters measured. Our results indicate that patients with more severe
      disease, as revealed by silent myocardial ischaemia, had lower levels of free t
      PA as a result of the excess of PAI-1.

PMID- 9663708
TI  - Measurement of plasma fibrinogen concentration by the prothrombin-time-derived
      method: applicability and limitations.
AB  - A prothrombin-time-derived method was used to measure plasma fibrinogen
      concentration (PFC) in 286 samples from 242 normal and 44 orally anticoagulated
      subjects. Absorbance changes at 405 nm (deltaOD) during the clotting process were
      obtained by an automatic coagulometer and their relationship with plasma
      fibrinogen concentration (range 90-1090 mg/dl), measured by the Clauss method,
      was investigated. A weighted linear regression between the deltaOD and the Clauss
      derived PFC values provided the best fit of the experimental data. The fitting
      equation was found to be reliable and accurate for PFC determination in normal
      subjects, whereas a systematic overestimate of fibrinogen level was demonstrated
      in plasma with high fibrinogen concentrations (> 400 mg/dl) and in plasma from
      anticoagulated patients. The systematic overestimate in the latter samples could
      be a result of an increased fibrin gel turbidity, as shown by in-vitro
      experiments using purified fibrinogen clotted by different thrombin
      concentrations. The PFC overestimate by the prothrombin-time-derived method could
      also be experimentally reproduced by competitively inhibiting thrombin-fibrinogen
      interaction by hirudin 54-65 peptide and the fibrinogen fragment E. A similar
      qualitative result was also found for the prothrombin-time-derived method in the
      presence of the Gly-Pro-Arg-Pro peptide, which competitively inhibits the end-to
      end fibrin aggregation process. Notably, under both the above experimental
      conditions, the Clauss method underestimated the PFC. On the other hand, the
      'clot recovery' method was minimally affected by the above inhibitors. These
      results indicate that the prothrombin-time-derived method is accurate and precise
      for most routine purposes. Its precision seems inadequate, however, under those
      conditions where the prothrombin time is prolonged (such as anticoagulant
      therapy) and in the presence of high fibrinogen levels.

PMID- 9663709
TI  - Circulating von Willebrand factor antigen II in atherosclerosis: a comparison
      with von Willebrand factor and soluble thrombomodulin.
AB  - von Willebrand factor antigen II (vWFAgII) is the 100 kDa propolypeptide of
      endothelial cell marker von Willebrand factor (vWF). Our aim was to determine the
      relationship between vWFAgII and mature vWF and an additional endothelial cell
      marker, soluble thrombomodulin, in atherosclerosis. To do this, we measured
      levels of all three by enzyme-linked immunosorbent assay in plasma obtained from
      24 patients with peripheral vascular disease (PVD), from 25 patients who survived
      a myocardial infarction [i.e. had ischaemic heart disease (IHD)], and from 47 age
      and sex-matched controls. We found raised levels of vWFAgII in PVD (57.3 +/-
      15.3 microg/dl; mean +/- standard deviation) and in IHD (53.4 +/- 19.2 microg/dl)
      compared with the controls (35.7 +/- 12.0 microg/dl; analysis of variance P <
      0.001). Raised levels of vWf were found in both groups of patients but raised
      soluble thrombomodulin was found only in patients with PVD. Levels of vWFAgII
      correlated with those of vWf (r = 0.45, P < 0.001) but not with soluble
      thrombomodulin (r = 0.14, P = 0.17), nor any of the major risk factors for
      atherosclerosis. Our brief study reports raised levels of vWFAgII in
      atherosclerosis. This may, like that of vWf, be related to endothelial cell
      damage, although the incomplete correlation between the two implies different
      metabolic and/or release mechanisms.

PMID- 9663710
TI  - Genetic polymorphisms of factor VII are not associated with arterial thrombosis.
AB  - A high plasma concentration of factor VII procoagulant activity is considered an
      independent risk factor for coronary heart disease. Recently, two polymorphisms
      of factor VII gene (insertion of a decanucleotide at -323 [A2], and the variant
      Q353) have been associated with 20-25% lower levels of this protein in plasma. In
      this study, the prevalence of these two factor VII polymorphisms were evaluated
      in relation to the development of acute thromboembolic events. Thus, we conducted
      three case-control studies of patients diagnosed with acute coronary syndromes,
      acute cerebrovascular events and deep venous thrombosis (101, 104 and 97 cases,
      respectively). No significant differences were detected in the prevalence of
      these polymorphisms between patients and controls, suggesting that the A1/A2 or
      R/Q alleles do not play an important role in the development of thromboembolic
      episodes.

PMID- 9663711
TI  - Atypical heparin-induced thrombocytopenia complicated by intracardiac thrombus,
      effectively treated with ultra-low-dose rt-PA lysis and recombinant hirudin
      (Lepirudin).
AB  - A serious retroperitoneal bleeding occurred in a 56-year-old male patient
      receiving unfractionated heparin due to multiple pulmonary embolism. After
      reducing the heparin dose, the patient developed a new pulmonary embolism and a
      large thrombus in the right atrium. Concomitantly, the platelet count dropped to
      a value of 29 g/l. Heparin-induced thrombocytopenia (HIT) was confirmed by a
      functional assay, the heparin-induced platelet activation (HIPA) assay, whereas
      the results of a platelet factor 4/heparin complex ELISA were repeatedly
      negative. This indicated that the patient's HIT antibodies were directed towards
      an antigen other than platelet factor 4/heparin complexes. For treatment of the
      atrial thrombus, an ultra-low-dose lysis with rt-PA (2 mg/h, intravenously) was
      administered for a period of 52 h, overlapping with systemic treatment with
      recombinant hirudin (Lepirudin, Refludan, 0.06-0.14 mg/kg/h intravenously). The
      aim was to enhance lysis of the thrombus without increasing the haematoma, and at
      the same time keep the risk of fulminant pulmonary embolism due to thrombus
      fragmentation as low as possible. The cardiac thrombus disappeared within 48 h,
      without new signs of pulmonary embolism. Platelet counts normalized within nine
      days.

PMID- 9663712
TI  - Hyperfibrinogenolysis in disseminated adenocarcinoma.
AB  - We present the case of a 42-year-old woman with a recently acquired bleeding
      tendency. Coagulation studies and response to antifibrinolytic therapy suggested
      primary hyperfibrinogenolysis: markedly low levels of fibrinogen and alpha2
      antiplasmin, normal levels of antithrombin III, protein C and protein S combined
      with an only borderline low number of platelets without evidence of
      microangiopathic haemolytic anaemia. A suspected causative adenocarcinoma of the
      lung was demonstrated. She was treated successfully with tranexamic acid and
      cryoprecipitate, until the tumor progressed and hyperfibrinogenolysis progressed
      to diffuse intravascular coagulation. Differential diagnosis of these coagulation
      disorders, with similar etiology, clinical and laboratory findings is reviewed.
      Therapeutic implications are discussed.